PMID- 27178944 TI - Magnetic hydrogel beads based on PVA/sodium alginate/laponite RD and studying their BSA adsorption. AB - In this study double physically crosslinked magnetic hydrogel beads were developed by a simple method including solution mixing of sodium alginate and poly(vinyl alcohol) (PVA) containing magnetic laponite RD (Rapid Dispersion). Sodium alginate and PVA were physically crosslinked by Ca(2+) and freezing thawing cycles, respectively. Magnetic laponite RD nanoparticles were incorporated into the system to create magnetic response and strengthen the hydrogels. All hybrids double physically crosslinked hydrogel beads were stable under different pH values without any disintegration. Furthermore, adsorption of bovine serum albumin (BSA) on the hydrogel beads was investigated on the subject of pH, ion strength, initial BSA concentration, and temperature. Nanocomposite beads exhibited maximum adsorption capacity for BSA at pH=4.5. The experimental adsorption isotherm data were well followed Langmuir model and based on this model the maximum adsorption capacity was obtained 127.3mgg(-1) at 308K. Thermodynamic parameters revealed spontaneous and monolayer adsorption of BSA on magnetic nanocomposites beads. PMID- 27178945 TI - Impact of dual-enzyme treatment on the octenylsuccinic anhydride esterification of soluble starch nanoparticle. AB - The hypothesis of improving the esterification of sugary maize soluble starch through dual-enzyme pretreatment was investigated. Native starch nanoparticle (NSP) was enzymatically pretreated using beta-amylase and transglucosidase (ESP) and then esterified with octenylsuccinic anhydride (OSA). The degree of substitution (DS), reaction efficiency (RE), molecular weight (Mw), molecular density (rho) and in vitro digestibility were determined. Fourier transform infrared spectroscopy and confocal laser scanning microscopy were used to analyze starch particle and its OS derivatives. The emulsification properties of OS-NSP and OS-ESP were also compared. The results showed that dual-enzyme modification increased the DS and RE of OSA modified starch particle compared with the control. Enzymatic modification had a thinning effect at the surface of starch particle, resulting in lower Mw. The extent of reduction in rho of OS-ESP was greater than that of OS-NSP. At equivalent DS, OSA modification of EPS was more effective than that of NPS in reducing digestibility. Also, there was brighter fluorescence spheres of OS-ESP in comparison to OS-NSP at equivalent DS, suggesting more OS groups were substituted on the chains near the branch points at less density areas. OS-ESP with higher DS (0.0197) had lower zeta-potential and average particle size for superior emulsion stabilization properties with high stability. The results revealed the OS-starch prepared under dual-enzyme pretreatment was a Pickering particle stabilizer for potential application in encapsulation and delivery of bioactive components. PMID- 27178946 TI - Structural characterization and in vitro antitumor activity of an acidic polysaccharide from Angelica sinensis (Oliv.) Diels. AB - A water-soluble polysaccharide extracted from the roots of Angelica sinensis (Oliv.) Diels, which is a traditional Chinese medicine herb, was fractioned and purified by Sephadex G-50 gel filtration chromatography. The structural characterization and antitumor activities of the purified polysaccharide fraction, named as ASP, were evaluated in the present study. ASP, which molecular weight was determined to be 80kDa by high-performance gel-permeation chromatography, is an acidic heteropolysaccharide consisting of glucuronic acid, glucose, arabinose and galactose in ratio of 1.00:1.70:1.85:5.02. It has a backbone composed of (1->3)-linked Galp, (1->6)-linked Galp and 2-OMe-(1->6) linked Galp with three branches attached to O-3 of 2-OMe-(1->6)-linked Galp and terminated with GlcpA and Araf, and all of Araf and the majority of Glcp are distributed in branches. Moreover, all of GlcpA were presented as (1->)-linked GlcpA in branches. In in vitro antitumor assays, ASP displayed cytotoxicity against HepG2 cells (34.32+/-3.50% at the concentration of 1mg/mL) and MCF-7 cells (28.90+/-1.50% at the concentration of 1mg/mL) in a dose-dependent manner, and ASP also showed mild inhibitory activity against A549 cells. PMID- 27178947 TI - Development of chitosan/beta-glycerophosphate/glycerol hydrogel as a thermosensitive coupling agent. AB - This work develops a dual-function thermosensitive hydrogel to prevent overheating, a side effect of focused ultrasound therapy. The proposed hydrogel has the components of chitosan, beta-glycerophosphate, and glycerol. Its thermosensitive sol-to-gel transition gives an instant signal of overheating without the need of any awkward sensing device. Impacts of varying component concentrations on the sol-to-gel temperature, rate, and degree of transparency are also investigated. Chemical structures and ultrasonic coefficients after heating are obtained with a Fourier transform infrared spectroscopy and ultrasonic measurement, respectively. Optimized formula of the proposed hydrogel is 0.5% chitosan, 5% beta-glycerophosphate, and 25% glycerol. This hydrogel has a high acoustic impedance (Z=1.8 Mrayl) close to that of human skin, high ultrasonic transmission (T=99%, which is normalized to water) from 25 to 55 degrees C, and low attenuation coefficient (alpha=4.0Np/m). These properties assure the success of dual functions of the hydrogel developed in this work. PMID- 27178948 TI - Inclusion complexes of HP-beta-cyclodextrin with agomelatine: Preparation, characterization, mechanism study and in vivo evaluation. AB - Agomelatine (AGM), is efficacious in both the acute phase and the continuation phase of depression. However, its poor water-solubility, low bioavailability and polymorphism limit its pharmacological effects. To address these problems, agomelatine-hydroxypropyl-beta-cyclodextrin inclusion complex (AGM/HPbeta-CD) was prepared successfully by freeze-drying. The products was evaluated by structural characterization, solubilization test, in-situ absorption of rat intestinal tract and pharmacokinetic study. In addition, thermodynamic studies were performed, the results indicated that the inclusion process was enthalpy-determined and exothermic nature of complexation, signifying the role of steric interactions in complex formation. Molecular docking of AGM with HPbeta-CD has been conducted as well to verify the experimental findings and predict the stable molecular structure of the inclusion complex. The in vivo data showed that, AGM was mainly absorbed in duodenum and jejunum by passive diffusion. AGM/HPbeta-CD inclusion complex displayed earlier Tmax and higher Cmax, and the AUC0-12h was approximately twice larger than its physical mixture. These results suggested that AGM/HPbeta-CD inclusion complex was established with 1:1 stoichiometry through the naphthalene group of AGM and it was deeply inserted into the cavity of HPbeta-CD, and the inclusion complex could significantly enhance the oral bioavailability of AGM. PMID- 27178949 TI - Starch gelatinization and in vitro digestibility behaviour after heat treatment: Comparison between plantain paste and piece of pulp. AB - Over the 65-100 degrees C range and at a water content of 1.6kgkg(-1)db, a comparison was conducted between plantain paste (dispersion made of flour and water) and pulp pieces after cooking to evaluate their respective degree of starch gelatinization (alpha) and in vitro digestibility. Below 76 degrees C and at 100 degrees C, the gelatinization behaviour of starch into pulp pieces and paste was similar, whereas at 85 degrees C a significant mean relative difference was observed in between. For alpha in the 0-1 range, pieces of plantain pulp exhibited a lower rapidly digestible starch fraction (30%) and a higher resistant starch fraction (33%) than the flour paste, suggesting some structural effects. Both Weibull and exponential models showed a good fit for alpha over temperature range and starch digestibility fractions over alpha. Although no explicit relationship was established between the intact pulp structure and grinded flour state of plantain, the evaluation of the degree of starch gelatinization and digestibility of a plantain flour paste, could be used to predict the gelatinization and digestibility behaviour of plantain starch in entire pieces of pulp. PMID- 27178950 TI - Surface patterned pH-sensitive fluorescence using beta-cyclodextrin functionalized poly(ethylene glycol). AB - This paper reports the development of a pH-responsive molecular pattern that shows specific and selective affinity for particular host-guest interactions, and its use as a pH fluorescent sensor. The pH-responsive boronate ester is formed via interactions between the diol group of beta-cyclodextrin (CD) and phenylboronic acid of poly(ethylene glycol), and is strategically designed to allow reversible formation of a molecular lining pattern. Printing on a versatile substrate provides a method to monitor the positioning of different molecules by using a pH-responsive boronate ester, allowing specific host-guest interactions on any surface. Confocal laser scanning microscopy, fluorescence spectroscopy, and (1)H NMR results indicate that the assembled CD monolayer can be removed by washing with an acidic pH buffer, demonstrating the presence of a boronate ester connective bridge, which is acid labile. Therefore, visualization of the pH responsive fluorescence sensor using a rhodamine-CD complex allows straightforward discrimination between different molecules on any substrate, thus facilitating application of this sensor in clinical diagnostics and environmental monitoring. PMID- 27178951 TI - Inulin: Properties, health benefits and food applications. AB - Inulin is a water soluble storage polysaccharide and belongs to a group of non digestible carbohydrates called fructans. Inulin has attained the GRAS status in USA and is extensively available in about 36,000 species of plants, amongst, chicory roots are considered as the richest source of inulin. Commonly, inulin is used as a prebiotic, fat replacer, sugar replacer, texture modifier and for the development of functional foods in order to improve health due to its beneficial role in gastric health. This review provides a deep insight about its production, physicochemical properties, role in combating various kinds of metabolic and diet related diseases and utilization as a functional ingredient in novel product development. PMID- 27178952 TI - Effect of pH on the rheological properties of borate crosslinked hydroxypropyl guar gum hydrogel and hydroxypropyl guar gum. AB - pH is an important factor affecting the performance of polymer fluid. The rheological properties of hydroxypropyl guar gum (HPG) base fluid and the structural strength, rheological properties, viscoelastic properties and thixotropy properties of HPG gel depend largely on the pH values. For the base fluid, an apparent viscosity-increasing effect was observed over the pH range from 7 to 11, and the apparent viscosity gradually decreased at pH 11.5-14, exhibiting electrostatic repulsion behavior and steric effects. For the HPG gel, at pH 7-12.5, the gel possessed higher apparent viscosity, higher elastic modulus (G'), lower tandelta (the ratio of the viscous modulus to the elastic modulus) and an "8"-shaped hysteresis loop, indicating stronger gel structure strength and the elastic dominant property. At pH 13-13.5, the gel samples exhibited the transition from a pseudoplastic fluid to a Newtonian fluid, and their viscosity, elastic modulus decreased but tandelta increased with the increase in pH values, exhibiting gradually weakened elastic properties. When the pH was 14, the gel mainly exhibited viscous characteristics. PMID- 27178953 TI - Electrospinnability of bionanocomposites with high nanocrystal loadings: The effect of nanocrystal surface characteristics. AB - This paper deals with the effect of solution properties and nanoparticle surface chemistry on the spinnability of a chitosan/polyethylene oxide (PEO) with high concentration (50wt%) of chitin and cellulose nanocrystals and the properties of the resultant nanocomposite fibers/fiber mats. Electrospinning dispersions with cellulose nanocrystals having sulphate surface groups showed poor spinnability compared to chitin nanocrystals with amide and amino groups. Chitin nanocrystal based dispersions showed good spinnability and continuous fiber formation whereas cellulose nanocrystal system showed discontinuous fibers and branching. The viscosity and surface tension are shown to impact this behavior, but conductivity did not. Poor spinnability observed for cellulose nanocrystal based fibers was attributed to the coagulation of negatively charged cellulose nanocrystals and positively charged chitosan. The study showed that the nanocrystal surface charge and interactions with the chitosan/PEO matrix have a significant impact on the spinnability of bionanocomposites. PMID- 27178954 TI - Properties and in vitro drug release of hyaluronic acid-hydroxyethyl cellulose hydrogels for transdermal delivery of isoliquiritigenin. AB - In the present study, the properties of hydrogel systems based on hyaluronic acid (HA)-hydroxyethyl cellulose (HEC) were investigated for effective transdermal delivery of isoliquiritigenin (ILTG). Hydrogels were synthesized by chemical cross-linking, and network structures were characterised using scanning electron microscopy (SEM) and surface area analyser. Texture properties and swelling of HA HEC hydrogels were found to be closely linked to cross-linker concentration and swelling medium. Water in HA-HEC hydrogels was found to exist mostly in the form of free water. The viscoelasticity and the network stabilization of the hydrogels were analysed via rheological studies. The release kinetics of the hydrogel followed Fickian diffusion mechanism. In an in vitro skin penetration study, the system substantially improved the delivery of ILTG into the skin. These results indicate that the hydrogel system composed of HA and HEC has potential as a transdermal delivery system, with cross-linking density and the swelling medium influencing the properties. PMID- 27178955 TI - Prilling and supercritical drying: A successful duo to produce core-shell polysaccharide aerogel beads for wound healing. AB - Bacterial infections often affect the wound, delaying healing and causing areas of necrosis. In this work, an aerogel in form of core-shell particles, able to prolong drug activity on wounds and to be easily removed was developed. Aerogel microcapsules consisted of a core made by amidated pectin hosting doxycycline, an antibiotic drug with a broad spectrum of action, and a shell consisting of high mannuronic content alginate. Particles were obtained by prilling using a coaxial nozzle for drop production and an ethanolic solution of CaCl2 as gelling promoter. The alcogels where dried using supercritical CO2. The influence of polysaccharides and drug concentrations on aerogel properties was evaluated. Spherical particles with high drug encapsulation efficiency (87%) correlated to alginate concentration in the processed liquid feeds were obtained. The release of the drug, mainly concentrated into the pectin core, was prolonged till 48h, and dependent on both drug/pectin ratio and alginate concentration. PMID- 27178956 TI - Calcium pectinate gel beads obtained from callus cultures pectins as promising systems for colon-targeted drug delivery. AB - Low methyl-esterified pectins obtained from the cell walls of the campion (SV, SV>300), tansy (TV, TV>300) and duckweed (LM, LM>300) callus cultures and apple pectin (AP, Classic AU 701) were used as the carriers for colon delivery of prednisolone. The pectins with molecular weight more than 300kDa (SV>300, TV>300, LM>300) formed gels which exhibited the higher gel strength. The higher gel strength of these gels appeared to be related to the higher Mw and the lower degree of methylesterification (DE) of these pectins. Release aspects of prednisolone in the simulated gastric (pH 1.25), intestinal (pH 7.0) and colonic (pH 7.0+pectinase) media were investigated. The LM-5%, AP-3% and AP-5% beads destroyed in simulated intestinal medium probably due to the higher DE of the LM and AP pectins. The SV>300-3% and TV>300-3% prednisolone loaded bead systems showed a high stability at pH 1.25 and pH 7.0. Prednisolone release occurred in a larger extent in colonic medium due to the enzymatic erosion of the beads. The SV>300-3% and TV>300-3% particles showed a more controlled release that appeared to be related to the lower DE, rhamnogalacturonan content, rhamnogalacturonan I branching and the higher linearity and Mw of the TV>300 and SV>300 pectins, as well as to the higher gel strength. This in vitro study suggests that calcium pectinate gel beads obtained from callus cultures pectins can be proposed as potential systems for colon-targeted drug delivery. PMID- 27178957 TI - Antibacterial activity of silver nanoparticles synthesized In-situ by solution spraying onto cellulose. AB - Spray technique was used for the adsorption of in-situ silver nanoparticles (AgNPs) onto and inside the surface of nano- and micro- fibrillar cellulose (NFC and MFC) as well as filter paper. The abundance of hydroxyl and carboxyl groups located in NFC and MFC are used to stabilize Ag ions (Ag(+)) which were then in situ reduced to (AgNPs) by chemical or UV reduction. The surface characteristic features, elemental analysis, particle size as well as size distribution of the obtained MFC, NFC and filter paper loaded with AgNPs were characterized via field emission scanning electron microscopy connected to energy dispersive X-ray spectroscopy (FESEM- EDX) and transmission electron microscopy (TEM). The associated chemical changes after growth of AgNPs onto the cellulose substrates were assessed by fourier transform infra-red (FT-IR) while the thermal stability of such systems were investigated by thermogravimetrical analyses (TGA). The antibacterial properties of AgNPs loaded NFC, MFC and filter paper as well was investigated against Escherichia Coli. The resulted data indicate that the particle size was found to be 11 and 26nm for AgNPs nucleated on NFC and MFC based papers respectively. The antibacterial activity of AgNPs loaded MFC exhibited higher antibacterial activity than that of AgNPs loaded NFC. Overall, the present research demonstrates facile and fast method for in-situ antibacterial AgNPs loading on cellulose substrates. PMID- 27178958 TI - Fabrication of poly(vinyl alcohol)-Carrageenan scaffolds for cryopreservation: Effect of composition on cell viability. AB - The present investigation reports the fabrication of three dimensional (3D), interconnected, highly porous, biodegradable scaffolds using freeze-gelation technique. The hydrogels prepared with different ratios (5:5, 6:4, 7:3, 8:2 and 9:1) of poly(vinyl alcohol) (PVA) and Carrageenan (Car) was lyophilized to obtain their respective scaffolds. The PVA-Car scaffolds were further characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR). The prepared scaffolds were found to be biodegradable and highly compatible with hemoglobin. Further, normal keratinocyte (HaCaT) and osteosarcoma (Saos-2) cells seeded on PVA-Car scaffolds were cryopreserved for 15days and their viability was checked at regular interval of 3days (0, 3, 6, 9, 12, 15 days) through MTT assay and fluorescence microscopy. Overall, the collective results indicate the scaffold constructs with 7:3 and 8:2 PVA-Car ratios possess ideal characteristics for tissue engineering applications and for long term cryopreservation of cells. PMID- 27178959 TI - Porous cellulose diacetate-SiO2 composite coating on polyethylene separator for high-performance lithium-ion battery. AB - The developments of high-performance lithium ion battery are eager to the separators with high ionic conductivity and thermal stability. In this work, a new way to adjust the comprehensive properties of inorganic-organic composite separator was investigated. The cellulose diacetate (CDA)-SiO2 composite coating is beneficial for improving the electrolyte wettability and the thermal stability of separators. Interestingly, the pore structure of composite coating can be regulated by the weight ratio of SiO2 precursor tetraethoxysilane (TEOS) in the coating solution. The electronic performance of lithium ion batteries assembled with modified separators are improved compared with the pristine PE separator. When weight ratio of TEOS in the coating solution was 9.4%, the composite separator shows the best comprehensive performance. Compared with the pristine PE separator, its meltdown temperature and the break-elongation at elevated temperature increased. More importantly, the discharge capacity and the capacity retention improved significantly. PMID- 27178960 TI - Nitrate decontamination through functionalized chitosan in brackish water. AB - N, N, N-Triethyl ammonium functionalized cross-linked chitosan beads (TEACCB) was prepared by alkylation of glutaraldehyde cross-linked chitosan beads to remove nitrate from brackish water. Physico-chemical characteristics of TEACCB were analyzed using FTIR, SEM, EDAX, TGA, DTA, BET surface area, swelling ratio and pHzpc. The maximum nitrate removal capacity of TEACCB was 2.26meq/g and is higher than other reported chitosan based adsorbents. Nitrate removal ratio in the presence and absence of common anions like chloride and sulphate demonstrated the selectively of TEACCB towards nitrate. The kinetic data of nitrate removal fitted well with the pseudo-second-order kinetic model. The thermodynamic parameters indicated that nitrate removal could be spontaneous and exothermic in nature. TEACCB was reused with 100% efficiency after regenerating with 0.05N HCl. Column study was carried out to remove nitrate from brackish water. These results are very significant to develop TEACCB based nitrate removal technology with great efficiency. PMID- 27178961 TI - Water desorption of cassava starch granules: A study based on thermogravimetric analysis of aqueous suspensions and humid powders. AB - This work reports on water desorption from cassava starch in relation with the structure and conditioning of granules in suspensions or after equilibration in desiccators. The experimental work is performed by thermogravimetric analysis with isothermal and non-isothermal protocols and interpreted to derive the activation energies and desorption frequencies according to the humidity range with no adjustable parameter. The analysis points out the different types of water interacting with the starch granules and relates the drying coefficients to their microscopic structure. The work helps clarifying contradictory and partial results from the literature. PMID- 27178962 TI - Multi-scale model for the hierarchical architecture of native cellulose hydrogels. AB - The structure of protiated and deuterated cellulose hydrogels has been investigated using a multi-technique approach combining small-angle scattering with diffraction, spectroscopy and microscopy. A model for the multi-scale structure of native cellulose hydrogels is proposed which highlights the essential role of water at different structural levels characterised by: (i) the existence of cellulose microfibrils containing an impermeable crystalline core surrounded by a partially hydrated paracrystalline shell, (ii) the creation of a strong network of cellulose microfibrils held together by hydrogen bonding to form cellulose ribbons and (iii) the differential behaviour of tightly bound water held within the ribbons compared to bulk solvent. Deuterium labelling provides an effective platform on which to further investigate the role of different plant cell wall polysaccharides in cellulose composite formation through the production of selectively deuterated cellulose composite hydrogels. PMID- 27178963 TI - Corrigendum to "Structure-function relationships of immunostimulatory polysaccharides: A review" [Carbohydr. Polym. 132 (2015) 378-396]. PMID- 27178964 TI - Device Technique Used in Skin Test Study. PMID- 27178965 TI - Reply. PMID- 27178966 TI - A Comprehensive Approach to the Management of Children and Adults with Chronic Granulomatous Disease. AB - Chronic granulomatous disease (CGD), a disease characterized by inadequate neutrophil killing of microbial pathogens, affects 4 to 5 per million live births. For many decades following its description, CGD was a fatal disease in childhood. With the development of effective preventive therapies and the early recognition of infectious complications, 90% of children with CGD now survive into adulthood. The management of CGD in adults includes unique challenges and potential disease manifestations. In this article, the authors discuss the current approach to the management of CGD in both children and adults. This includes a focus on the importance of a comprehensive multidisciplinary approach in the care of CGD and its potential complications. In addition, a novel approach to improving education about CGD, and subsequently improving adherence to preventive therapies, is discussed. PMID- 27178968 TI - Minimally invasive corticotomy in orthodontics using a three-dimensional printed CAD/CAM surgical guide. AB - The aim of this prospective study was to evaluate the effectiveness of an innovative, minimally invasive, flapless corticotomy procedure in orthodontics. The STROBE guidelines were followed. Ten patients with severe dental crowding and a class I molar relationship were selected to receive orthodontic treatment with clear aligners and corticotomy-facilitated orthodontics. The mean age of these patients was 21 years (range 17-28, standard deviation 6.08 years); the male to female ratio was 2:1. The main outcome was a reduction in the total treatment time to correct dental crowding. The secondary outcomes were periodontal index changes, the degree of root resorption, and patient perceptions of the method used, assessed using the short-form Oral Health Impact Profile (OHIP-14). The occurrence of early surgical complications or unexpected events was also recorded. All patients completed the treatment to correct dental crowding. The average treatment time was reduced by two-thirds. The procedure did not significantly modify the periodontal indices or oral health-related quality of life. No early surgical complications or unexpected events were observed. In short, the results indicate that this new procedure is safe and accelerates tooth movement without periodontal complications or discomfort. However, the efficacy of this procedure must be confirmed in controlled clinical trials. PMID- 27178967 TI - Tristetraprolin binding site atlas in the macrophage transcriptome reveals a switch for inflammation resolution. AB - Precise regulation of mRNA decay is fundamental for robust yet not exaggerated inflammatory responses to pathogens. However, a global model integrating regulation and functional consequences of inflammation-associated mRNA decay remains to be established. Using time-resolved high-resolution RNA binding analysis of the mRNA-destabilizing protein tristetraprolin (TTP), an inflammation limiting factor, we qualitatively and quantitatively characterize TTP binding positions in the transcriptome of immunostimulated macrophages. We identify pervasive destabilizing and non-destabilizing TTP binding, including a robust intronic binding, showing that TTP binding is not sufficient for mRNA destabilization. A low degree of flanking RNA structuredness distinguishes occupied from silent binding motifs. By functionally relating TTP binding sites to mRNA stability and levels, we identify a TTP-controlled switch for the transition from inflammatory into the resolution phase of the macrophage immune response. Mapping of binding positions of the mRNA-stabilizing protein HuR reveals little target and functional overlap with TTP, implying a limited co regulation of inflammatory mRNA decay by these proteins. Our study establishes a functionally annotated and navigable transcriptome-wide atlas (http://ttp atlas.univie.ac.at) of cis-acting elements controlling mRNA decay in inflammation. PMID- 27178969 TI - Strengthening leadership as a catalyst for enhanced patient safety culture: a repeated cross-sectional experimental study. AB - OBJECTIVES: Current literature emphasises that clinical leaders are in a position to enable a culture of safety, and that the safety culture is a performance mediator with the potential to influence patient outcomes. This paper aims to investigate staff's perceptions of patient safety culture in a Danish psychiatric department before and after a leadership intervention. METHODS: A repeated cross sectional experimental study by design was applied. In 2 surveys, healthcare staff were asked about their perceptions of the patient safety culture using the 7 patient safety culture dimensions in the Safety Attitudes Questionnaire. To broaden knowledge and strengthen leadership skills, a multicomponent programme consisting of academic input, exercises, reflections and discussions, networking, and action learning was implemented among the clinical area level leaders. RESULTS: In total, 358 and 325 staff members participated before and after the intervention, respectively. 19 of the staff members were clinical area level leaders. In both surveys, the response rate was >75%. The proportion of frontline staff with positive attitudes improved by >=5% for 5 of the 7 patient safety culture dimensions over time. 6 patient safety culture dimensions became more positive (increase in mean) (p<0.05). Frontline staff became more positive on all dimensions except stress recognition (p<0.05). For the leaders, the opposite was the case (p<0.05). Staff leaving the department after the first measurement had rated job satisfaction lower than the staff staying on (p<0.05). CONCLUSIONS: The improvements documented in the patient safety culture are remarkable, and imply that strengthening the leadership can act as a significant catalyst for patient safety culture improvement. Further studies using a longitudinal study design are recommended to investigate the mechanism behind leadership's influence on patient safety culture, sustainability of improvements over time, and the association of change in the patient safety culture measures with change in psychiatric patient safety outcomes. PMID- 27178970 TI - Prescribed opioids in primary care: cross-sectional and longitudinal analyses of influence of patient and practice characteristics. AB - OBJECTIVES: To examine trends in opioid prescribing in primary care, identify patient and general practice characteristics associated with long-term and stronger opioid prescribing, and identify associations with changes in opioid prescribing. DESIGN: Trend, cross-sectional and longitudinal analyses of routinely recorded patient data. SETTING: 111 primary care practices in Leeds and Bradford, UK. PARTICIPANTS: We observed 471 828 patient-years in which all patients represented had at least 1 opioid prescription between April 2005 and March 2012. A cross-sectional analysis included 99 847 patients prescribed opioids between April 2011 and March 2012. A longitudinal analysis included 49 065 patient-years between April 2008 and March 2012. We excluded patients with cancer or treated for substance misuse. MAIN OUTCOME MEASURES: Long-term opioid prescribing (4 or more prescriptions within 12 months), stronger opioid prescribing and stepping up to or down from stronger opioids. RESULTS: Opioid prescribing in the adult population almost doubled for weaker opioids over 2005 2012 and rose over sixfold for stronger opioids. There was marked variation among general practices in the odds of patients stepping up to stronger opioids compared with those not stepping up (range 0.31-3.36), unexplained by practice level variables. Stepping up to stronger opioids was most strongly associated with being underweight (adjusted OR 3.26, 1.49 to 7.17), increasing polypharmacy (4.15, 3.26 to 5.29 for 10 or more repeat prescriptions), increasing numbers of primary care appointments (3.04, 2.48 to 3.73 for over 12 appointments in the year) and referrals to specialist pain services (5.17, 4.37 to 6.12). Compared with women under 50 years, men under 50 were less likely to step down once prescribed stronger opioids (0.53, 0.37 to 0.75). CONCLUSIONS: While clinicians should be alert to patients at risk of escalated opioid prescribing, much prescribing variation may be attributable to clinical behaviour. Effective strategies targeting clinicians and patients are needed to curb rising prescribing, especially of stronger opioids. PMID- 27178971 TI - Role of sTREM-1 in predicting mortality of infection: a systematic review and meta-analysis. AB - OBJECTIVES: Several studies have investigated the prognostic value of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in patients with infection. However, the result was controversial. Thus, the purpose of the present meta-analysis was to determine the prognostic value of the sTREM-1 level in predicting mortality at the initial stage of infection. METHODS: The literature was searched in the PubMed, EMBASE, Web of Knowledge and Cochrane databases. A 2*2 contingency table was constructed on the basis of mortality and sTREM-1 levels in patients with infection. 2 authors independently judged study eligibility and extracted data. The prognostic value of sTREM-1 in predicting mortality was determined using a bivariate meta-analysis model. Q-test and I(2) index were used to test heterogeneity. RESULTS: 9 studies were selected from 803 studies. An elevated sTREM-1 level was associated with a higher risk of death in infection, with pooled risk ratio (RR) was 2.54 (95% CI 1.77 to 3.65) using a random-effects model (I(2)=53.8%). With the bivariate random-effects regression model, the pooled sensitivity and specificity of sTREM-1 to predict mortality in infection were 0.75 (95% CI 0.61 to 0.86) and 0.66 (95% CI 0.54 to 0.75), respectively. The diagnostic OR was 6 (95% CI 3 to 10). The overall area under the summary receiver operator characteristic (SROC) curve was 0.76 (95% CI 0.72 to 0.79). When we calculated the sepsis subgroup, the pooled RR was 2.98 (95% CI 2.19 to 4.40). The pooled sensitivity and specificity were 0.74 (95% CI 0.58 to 0.85) and 0.72 (95% CI 0.62 to 0.80), respectively. The overall area under the SROC curve was 0.78 (95% CI 0.74 to 0.81). CONCLUSIONS: Elevated sTREM-1 concentrations had a moderate prognostic significance in assessing the mortality of infection in adult patients. However, sTREM-1 alone is insufficient to predict mortality as a biomarker. PMID- 27178972 TI - Stroke survivors', caregivers' and GPs' attitudes towards a polypill for the secondary prevention of stroke: a qualitative interview study. AB - OBJECTIVES: To understand the perspectives of stroke survivors, caregivers and general practitioners (GPs) on a polypill approach, consisting of blood pressure and cholesterol-lowering therapies, with or without aspirin, for the secondary prevention of stroke. METHODS: A qualitative interview study was undertaken in 5 GP surgeries in the East of England. 28 survivors of stroke/transient ischaemic attack (TIA) were interviewed, 14 of them with a caregiver present, along with a convenience sample of 5 GPs, to assess attitudes towards a polypill and future use. Topic guides explored participants attitudes, potential uptake and long-term use, management of polypill medication and factors influencing the decision to prescribe. Data were analysed using a grounded theory approach. Key themes are presented and illustrated with verbatim quotes. RESULTS: The analysis identified 3 key themes: polypill benefits, polypill concerns and polypill lessons for implementation. Stroke/TIA survivors were positive about the polypill concept and considered it acceptable in the secondary prevention of stroke. Perceived benefits of a polypill included convenience resulting in improved adherence and reduced burden of treatment. Caregivers felt that a polypill would improve medication-taking practices, and GPs were open to prescribing it to those at increased cardiovascular risk. However, concerns raised included whether a polypill provided equivalent therapeutic benefit, side effects through combining medications, consequences of non-adherence, lack of flexibility in regulating dosage, disruption to current treatment and suitability to the wider stroke population. CONCLUSIONS: Participants acknowledged potential advantages in a polypill approach for secondary prevention of stroke; however, significant concerns remain. Further research on the efficacy of a polypill is needed to reassure practitioners whose concerns around inflexibility and treatment suitability are likely to influence the decision to prescribe a polypill for secondary prevention of stroke. Acceptability among survivors, caregivers and GPs is likely to determine the uptake and subsequent use of a polypill in the future. PMID- 27178973 TI - Economic evaluation of manual therapy for musculoskeletal diseases: a protocol for a systematic review and narrative synthesis of evidence. AB - INTRODUCTION: Manual therapy is the non-surgical conservative management of musculoskeletal disorders using the practitioner's hands on the patient's body for diagnosing and treating disease. The aim of this study is to systematically review trial-based economic evaluations of manual therapy relative to other interventions used for the management of musculoskeletal diseases. METHODS AND ANALYSIS: Randomised clinical trials (RCTs) on the economic evaluation of manual therapy for musculoskeletal diseases will be included in the review. The following databases will be searched from their inception: Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Econlit, Mantis, Index to Chiropractic Literature, Science Citation Index, Social Science Citation Index, Allied and Complementary Medicine Database (AMED), Cochrane Database of Systematic Reviews (CDSR), National Health Service Database of Abstracts of Reviews of Effects (NHS DARE), National Health Service Health Technology Assessment Database (NHS HTA), National Health Service Economic Evaluation Database (NHS EED), CENTRAL, five Korean medical databases (Oriental Medicine Advanced Searching Integrated System (OASIS), Research Information Service System (RISS), DBPIA, Korean Traditional Knowledge Portal (KTKP) and KoreaMed) and three Chinese databases (China National Knowledge Infrastructure (CNKI), VIP and Wanfang). The evidence for the cost-effectiveness, cost-utility and cost-benefit of manual therapy for musculoskeletal diseases will be assessed as the primary outcome. Health-related quality of life and adverse effects will be assessed as secondary outcomes. We will critically appraise the included studies using the Cochrane risk of bias tool and the Drummond checklist. Results will be summarised using Slavin's qualitative best-evidence synthesis approach. ETHICS AND DISSEMINATION: The results of the study will be disseminated via a peer-reviewed journal and/or conference presentations. TRIAL REGISTRATION NUMBER: PROSPERO CRD42015026757. PMID- 27178974 TI - General practitioners' justifications for therapeutic inertia in cardiovascular prevention: an empirically grounded typology. AB - OBJECTIVE: To construct a typology of general practitioners' (GPs) responses regarding their justification of therapeutic inertia in cardiovascular primary prevention for high-risk patients with hypertension. DESIGN: Empirically grounded construction of typology. Types were defined by attributes derived from the qualitative analysis of GPs' reported reasons for inaction. PARTICIPANTS: 256 GPs randomised in the intervention group of a cluster randomised controlled trial. SETTING: GPs members of 23 French Regional Colleges of Teachers in General Practice, included in the EffectS of a multifaceted intervention on CArdiovascular risk factors in high-risk hyPErtensive patients (ESCAPE) trial. DATA COLLECTION AND ANALYSIS: The database consisted of 2638 written responses given by the GPs to an open-ended question asking for the reasons why drug treatment was not changed as suggested by the national guidelines. All answers were coded using constant comparison analysis. A matrix analysis of codes per GP allowed the construction of a response typology, where types were defined by codes as attributes. Initial coding and definition of types were performed independently by two teams. RESULTS: Initial coding resulted in a list of 69 codes in the final codebook, representing 4764 coded references in the question responses. A typology including seven types was constructed. 100 GPs were allocated to one and only one of these types, while 25 GPs did not provide enough data to allow classification. Types (numbers of GPs allocated) were: 'optimists' (28), 'negotiators' (20), 'checkers' (15), 'contextualisers' (13), 'cautious' (11), 'rounders' (8) and 'scientists' (5). For the 36 GPs that provided 50 or more coded references, analysis of the code evolution over time and across patients showed a consistent belonging to the initial type for any given GP. CONCLUSION: This typology could provide GPs with some insight into their general ways of considering changes in the treatment/management of cardiovascular risk factors and guide design of specific physician-centred interventions to reduce inappropriate inaction. TRIAL REGISTRATION NUMBER: NCT00348855. PMID- 27178975 TI - A qualitative study of diverse providers' behaviour in response to commissioners, patients and innovators in England: research protocol. AB - INTRODUCTION: The variety of organisations providing National Health Service (NHS)-funded services in England is growing. Besides NHS hospitals and general practitioners (GPs), they include corporations, social enterprises, voluntary organisations and others. The degree to which these organisational types vary, however, in the ways they manage and provide services and in the outcomes for service quality, patient experience and innovation, remains unclear. This research will help those who commission NHS services select among the different types of organisation for different tasks. RESEARCH QUESTIONS: The main research questions are how organisationally diverse NHS-funded service providers vary in their responsiveness to patient choice, NHS commissioning and policy changes; and their patterns of innovation. We aim to assess the implications for NHS commissioning and managerial practice which follow from these differences. METHODS AND ANALYSIS: Systematic qualitative comparison across a purposive sample (c.12) of providers selected for maximum variety of organisational type, with qualitative studies of patient experience and choice (in the same sites). We focus is on NHS services heavily used by older people at high risk of hospital admission: community health services; out-of-hours primary care; and secondary care (planned orthopaedics or ophthalmology). The expected outputs will be evidence-based schemas showing how patterns of service development and delivery typically vary between different organisational types of provider. ETHICS, BENEFITS AND DISSEMINATION: We will ensure informants' organisational and individual anonymity when dealing with high profile case studies and a competitive health economy. The frail elderly is a key demographic sector with significant policy and financial implications. For NHS commissioners, patients, doctors and other stakeholders, the main outcome will be better knowledge about the relative merits of different kinds of healthcare provider. Dissemination will make use of strategies suggested by patient and public involvement, as well as DH and service-specific outlets. PMID- 27178976 TI - Can patients be 'attached' to healthcare providers? An observational study to measure attachment phenomena in patient-provider relationships. AB - OBJECTIVES: To develop and assess the validity of measures of patients' attachment-related perceptions of experiences with healthcare providers (HCPs). SETTING: Online survey. PARTICIPANTS: 181 people provided consent and 119 completed the survey (66%). Most participants were women (80%). PRIMARY AND SECONDARY OUTCOME MEASURES: Questions were developed to assess possible attachment functions served by an HCP and patients' attachment-related attitudes towards an HCP. Scales were constructed based on exploratory factor analysis. Measures of adult attachment, therapeutic alliance, perceived HCP characteristics and health utilisation were used to validate scales. RESULTS: Possible safe haven and secure base functions served by HCPs were strongly endorsed. A model with good fit (root mean square error of approximation=0.056) yielded 3 factors: 'HCP experienced as supportive and safe' (SUPPORT, alpha=0.94), 'HCP experienced as aversive' (AVERSE, alpha=0.86) and 'more and closer contact wanted with HCP' (WANT, alpha=0.85). SUPPORT was correlated with positive HCP characteristics and not with attachment insecurity. AVERSE was inversely correlated with positive HCP attributes and correlated with attachment insecurity. WANT was unrelated to positive HCP attributes, but correlated with attachment insecurity. Frequency of HCP contact was related to WANT (Kruskal-Wallis=21.9, p<0.001) and SUPPORT (Kruskal-Wallis=13.2, p=0.02), but not to AVERSE (Kruskal-Wallis=1.7, p=0.89). CONCLUSIONS: Patients attribute attachment functions of secure base and safe haven to HCPs. SUPPORT is related to positive appraisal of HCP characteristics; AVERSE is associated with discomfort in the HCP relationship that is related with perceived HCP characteristics and patients' insecure attachment; WANT is associated with unmet needs for connection with an HCP related to insecure attachment, but not to perceived HCP characteristics. These scales may be useful in studying the application of attachment theory to the HCP-patient relationship. PMID- 27178977 TI - Training primary care physicians to offer their patients faecal occult blood testing and colonoscopy for colorectal cancer screening on an equal basis: a pilot intervention with before-after and parallel group surveys. AB - OBJECTIVES: Primary care physicians (PCPs) should prescribe faecal immunochemical testing (FIT) or colonoscopy for colorectal cancer screening based on their patient's values and preferences. However, there are wide variations between PCPs in the screening method prescribed. The objective was to assess the impact of an educational intervention on PCPs' intent to offer FIT or colonoscopy on an equal basis. DESIGN: Survey before and after training seminars, with a parallel comparison through a mailed survey to PCPs not attending the training seminars. SETTING: All PCPs in the canton of Vaud, Switzerland. PARTICIPANTS: Of 592 eligible PCPs, 133 (22%) attended a seminar and 106 (80%) filled both surveys. 109 (24%) PCPs who did not attend the seminars returned the mailed survey. INTERVENTION: A 2 h-long interactive seminar targeting PCP knowledge, skills and attitudes regarding offering a choice of colorectal cancer (CRC) screening options. OUTCOME MEASURES: The primary outcome was PCP intention of having their patients screened with FIT and colonoscopy in equal proportions (between 40% and 60% each). Secondary outcomes were the perceived role of PCPs in screening decisions (from paternalistic to informed decision-making) and correct answer to a clinical vignette. RESULTS: Before the seminars, 8% of PCPs reported that they had equal proportions of their patients screened for CRC by FIT and colonoscopy; after the seminar, 33% foresaw having their patients screened in equal proportions (p<0.001). Among those not attending, there was no change (13% vs 14%, p=0.8). Of those attending, there was no change in their perceived role in screening decisions, while the proportion responding correctly to a clinical vignette increased (88-99%, p<0.001). CONCLUSIONS: An interactive training seminar increased the proportion of physicians with the intention to prescribe FIT and colonoscopy in equal proportions. PMID- 27178978 TI - Exploring the views of GPs, people with dementia and their carers on assistive technology: a qualitative study. AB - OBJECTIVES: To explore the views and experiences of people with dementia, their family carers and general practitioners (GPs) on their knowledge and experience of accessing information about, and use of, assistive technology (AT) in dementia care. DESIGN: Qualitative methods with semistructured interviews and thematic analysis. PARTICIPANTS: 56 participants comprising 17 GPs, 13 people with dementia and 26 family carers. SETTING: Community care settings in the North East of England. RESULTS: 4 main themes emerged: awareness and experience of AT; accessing information on AT; roles and responsibilities in the current care system and the future commissioning of AT services. All participants had practical experience of witnessing AT being used in practice. For people with dementia and their families, knowledge was usually gained from personal experience rather than from health and social care professionals. For GPs, knowledge was largely gained through experiential, patient-led learning. All groups acknowledged the important role of the voluntary sector but agreed a need for clear information pathways for AT; such pathways were perceived to be essential to both service providers and service commissioners. CONCLUSIONS: People with dementia and their family carers appear to be mainly responsible for driving a gradual increase in both awareness and the use of AT in dementia care. GPs should be equipped with the relevant knowledge to ensure families living with dementia receive appropriate information and support to enable them to live independently for as long as possible. There is an urgent need to simplify current complex community care pathways; as demonstrated in other chronic health conditions, a single point of access and a named lead professional may improve future care. PMID- 27178980 TI - Personalised long-term follow-up of cochlear implant patients using remote care, compared with those on the standard care pathway: study protocol for a feasibility randomised controlled trial. AB - INTRODUCTION: Many resources are required to provide postoperative care to patients who receive a cochlear implant. The implant service commits to lifetime follow-up. The patient commits to regular adjustment and rehabilitation appointments in the first year and annual follow-up appointments thereafter. Offering remote follow-up may result in more stable hearing, reduced patient travel expense, time and disruption, more empowered patients, greater equality in service delivery and more freedom to optimise the allocation of clinic resources. METHODS AND ANALYSIS: This will be a two-arm feasibility randomised controlled trial (RCT) involving 60 adults using cochlear implants with at least 6 months device experience in a 6-month clinical trial of remote care. This project will design, implement and evaluate a person-centred long-term follow-up pathway for people using cochlear implants offering a triple approach of remote and self monitoring, self-adjustment of device and a personalised online support tool for home speech recognition testing, information, self-rehabilitation, advice, equipment training and troubleshooting. The main outcome measure is patient activation. Secondary outcomes are stability and quality of hearing, stability of quality of life, clinic resources, patient and clinician experience, and any adverse events associated with remote care. We will examine the acceptability of remote care to service users and clinicians, the willingness of participants to be randomised, and attrition rates. We will estimate numbers required to plan a fully powered RCT. ETHICS AND DISSEMINATION: Ethical approval was received from North West-Greater Manchester South Research Ethics Committee (15/NW/0860) and the University of Southampton Research Governance Office (ERGO 15329). RESULTS: Results will be disseminated in the clinical and scientific communities and also to the patient population via peer-reviewed research publications both online and in print, conference and meeting presentations, posters, newsletter articles, website reports and social media. TRIAL REGISTRATION NUMBER: ISRCTN14644286; Pre results. PMID- 27178979 TI - Pregnancy outcomes in Lebanese women with multiple sclerosis (the LeMS study): a prospective multicentre study. AB - OBJECTIVE: The Lebanese Multiple Sclerosis (LeMS) study aims to assess the influence of pregnancy and delivery on the clinical course of multiple sclerosis (MS) in Lebanese women. SETTING: This prospective multicentre study took place in three MS referral university medical centres in Lebanon. PARTICIPANTS: Included were 29 women over 18 years who had been diagnosed with MS according to the McDonald criteria, and became pregnant between 1995 and 2015. Participating women should have stopped treatment 3 months before conception and become pregnant after the onset of MS. Women were followed up from 1 year preconceptionally and for 4 years postpartum. MAIN OUTCOME MEASURES: The annualised relapse rates per participant during each 3-month period during pregnancy and each year postpartum were compared with the relapse rate during the year before pregnancy using the paired two-tailed t test. p Values <0.05 were considered statistically significant for all analyses (95% CI). RESULTS: 64 full-term pregnancies were recorded. All pregnancies (100%) resulted in live births, with no complications or other diseases. In comparison with the prepregnancy year, in which the mean relapse rate+/-SE was 0.17+/-0.07, there was a significant reduction in the relapse rate during pregnancy and in the first year postpartum (p=0.02), but an increase in the rate in the second year postpartum (0.21+/-0.08). Thereafter, from the third year postpartum through the following fourth year, the annualised relapse rate fell slightly but did not differ from the annualised relapse rate recorded in the prepregnancy year (0.17+/-0.07). CONCLUSIONS: Pregnancy in Lebanese women with MS does not seem to increase the risk of complications. No relapses were observed during pregnancy and in the first year postpartum; however, relapses rebounded in the second year postpartum, and over the long term, returned to the levels that preceded pregnancy. PMID- 27178981 TI - Is omission of free text records a possible source of data loss and bias in Clinical Practice Research Datalink studies? A case-control study. AB - OBJECTIVES: To estimate data loss and bias in studies of Clinical Practice Research Datalink (CPRD) data that restrict analyses to Read codes, omitting anything recorded as text. DESIGN: Matched case-control study. SETTING: Patients contributing data to the CPRD. PARTICIPANTS: 4915 bladder and 3635 pancreatic, cancer cases diagnosed between 1 January 2000 and 31 December 2009, matched on age, sex and general practitioner practice to up to 5 controls (bladder: n=21 718; pancreas: n=16 459). The analysis period was the year before cancer diagnosis. PRIMARY AND SECONDARY OUTCOME MEASURES: Frequency of haematuria, jaundice and abdominal pain, grouped by recording style: Read code or text-only (ie, hidden text). The association between recording style and case-control status (chi(2) test). For each feature, the odds ratio (OR; conditional logistic regression) and positive predictive value (PPV; Bayes' theorem) for cancer, before and after addition of hidden text records. RESULTS: Of the 20 958 total records of the features, 7951 (38%) were recorded in hidden text. Hidden text recording was more strongly associated with controls than with cases for haematuria (140/336=42% vs 556/3147=18%) in bladder cancer (chi(2) test, p<0.001), and for jaundice (21/31=67% vs 463/1565=30%, p<0.0001) and abdominal pain (323/1126=29% vs 397/1789=22%, p<0.001) in pancreatic cancer. Adding hidden text records corrected PPVs of haematuria for bladder cancer from 4.0% (95% CI 3.5% to 4.6%) to 2.9% (2.6% to 3.2%), and of jaundice for pancreatic cancer from 12.8% (7.3% to 21.6%) to 6.3% (4.5% to 8.7%). Adding hidden text records did not alter the PPV of abdominal pain for bladder (codes: 0.14%, 0.13% to 0.16% vs codes plus hidden text: 0.14%, 0.13% to 0.15%) or pancreatic (0.23%, 0.21% to 0.25% vs 0.21%, 0.20% to 0.22%) cancer. CONCLUSIONS: Omission of text records from CPRD studies introduces bias that inflates outcome measures for recognised alarm symptoms. This potentially reinforces clinicians' views of the known importance of these symptoms, marginalising the significance of 'low-risk but not no-risk' symptoms. PMID- 27178983 TI - Progression-Free Survival, Response Rate, and Disease Control Rate as Predictors of Overall Survival in Phase III Randomized Controlled Trials Evaluating the First-Line Chemotherapy for Advanced, Locally Advanced, and Recurrent Non-Small Cell Lung Carcinoma. AB - INTRODUCTION: Recent improvements in chemotherapy agents have prolonged postprogression survival of non-small cell lung cancer. Thus, primary outcomes other than overall survival (OS) have been frequently used for recent phase III trials to obtain quick results. However, no systematic review had assessed whether progression-free survival (PFS), response rate (RR), and disease control rate (DCR) can serve as surrogates for OS at the trial level in the phase III first-line chemotherapy setting. METHODS: We included phase III randomized clinical trials (RCTs) comparing two arms that were reported as a full article regardless of their primary end point. We included only RCTs that evaluated chemonaive patients with advanced, locally advanced, or metastatic non-small cell lung cancer and were published after January 1, 2005. We systematically searched four public electronic databases. Two investigators independently screened and scrutinized candidate articles. How surrogate outcomes represented hazard ratios (HRs) for OS was examined. RESULTS: Among 1907 articles, we ultimately found 44 eligible articles covering 22,709 subjects. HR for PFS, median PFS in the experimental arm minus median PFS in the control arm in months, OR for RR (ORrr), and OR for DCR were evaluated in 34, 35, 44, and 35 RCTs, respectively. HR for OS (HRos), median PFS in the experimental arm minus median PFS in the control arm, ORrr, and OR for DCR had weighted Spearman's rank correlation coefficients with an HRos of 0.496, 0.477, 0.570, and 0.470, respectively; the standardized weighted regression coefficients were 0.439, -0.376, -0.605, and -0.381, respectively; and the adjusted weighted coefficients of determination were 0.224, 0.161, 0.350, and 0.176, respectively. CONCLUSIONS: ORrr, followed by HRpfs, had the strongest association with HRos at the trial level. However, these measures were not strong enough to replace OS. PMID- 27178984 TI - Effect of First-Line Treatment on Myeloid-Derived Suppressor Cells' Subpopulations in the Peripheral Blood of Patients with Non-Small Cell Lung Cancer. AB - INTRODUCTION: Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature cells of myeloid origin whose expression is induced by, among others things, vascular endothelial growth factor. We have previously identified two monocytic and one granulocytic MDSC subpopulations associated with the clinical outcome in patients with non-small cell lung cancer (NSCLC). The aim of the present study was to evaluate the effect of chemotherapy on these MDSC subpopulations. METHODS: Circulating immune cells from 46 patients with unresectable NSCLC were analyzed by flow cytometry before the initiation of chemotherapy and after three cycles. Changes in the frequencies of the MDSC subpopulations were correlated with clinical outcome. RESULTS: Chemotherapy had no uniform effect on either the number or the functionality of monocytic and granulocytic MDSCs. However, three cycles of bevacizumab-containing regimens significantly reduced the percentage of the granulocytic-MDSCs compared with non bevacizumab-based regimens (p = 0.0086). At the time of evaluation of response, disease progression was associated with significantly higher levels of all three MDSC subpopulations compared with in patients with disease control. Iotan patients with disease progression after three cycles of chemotherapy, the percentage of CD15-positive monocytic MDSCs was significantly increased compared with baseline. CONCLUSIONS: In the peripheral blood of patients with NSCLC, bevacizumab-based chemotherapy significantly reduced the levels of granulocytic MDSCs. An increase in the levels of CD15-positive monocytic MDSCs was associated with poor response to treatment and disease progression, providing evidence of their clinical relevance in patients with NSCLC. PMID- 27178982 TI - Zeb1 controls neuron differentiation and germinal zone exit by a mesenchymal epithelial-like transition. AB - In the developing mammalian brain, differentiating neurons mature morphologically via neuronal polarity programs. Despite discovery of polarity pathways acting concurrently with differentiation, it's unclear how neurons traverse complex polarity transitions or how neuronal progenitors delay polarization during development. We report that zinc finger and homeobox transcription factor-1 (Zeb1), a master regulator of epithelial polarity, controls neuronal differentiation by transcriptionally repressing polarity genes in neuronal progenitors. Necessity-sufficiency testing and functional target screening in cerebellar granule neuron progenitors (GNPs) reveal that Zeb1 inhibits polarization and retains progenitors in their germinal zone (GZ). Zeb1 expression is elevated in the Sonic Hedgehog (SHH) medulloblastoma subgroup originating from GNPs with persistent SHH activation. Restored polarity signaling promotes differentiation and rescues GZ exit, suggesting a model for future differentiative therapies. These results reveal unexpected parallels between neuronal differentiation and mesenchymal-to-epithelial transition and suggest that active polarity inhibition contributes to altered GZ exit in pediatric brain cancers. PMID- 27178986 TI - Rheumatoid arthritis onset in postmenopausal women: Does the ACPA seropositive subset result from genetic effects, estrogen deficiency, skewed profile of CD4(+) T-cells, and their interactions? AB - Rheumatoid arthritis (RA) incidence displays a differentiated age-dependent female-to-male ratio in which women outnumber men. Evidence that the peak incidence of RA in women coincides with menopause age, suggests a potential estrogenic role to disease etiology. Estrogens exert physiologically both stimulatory and inhibitory effects on the immune system. Epidemiologic and animal model studies with estrogen deprivation or supplementation suggested estrogens as to play, mainly, a protective role in RA immunopathology. In this review, we propose that some yet unidentified disturbances associated with estrogen circulating levels, differentiated by the menopausal status, play a major role in women's RA susceptibility. We focus on the interaction between estrogen deprivation and genetic risk alleles for anti-citrullinated protein antibodies (ACPA) seropositive RA, as a major driving force for increased immune reactivity and RA susceptibility, in postmenopausal women. This opens up new fields for research concerning the association among different irregular estrogenic conditions, the cytokine milieu, and age/menopausal status bias in RA. PMID- 27178985 TI - Patient crossover and potentially avoidable repeat computed tomography exams across a health information exchange. AB - OBJECTIVE: The purpose of this study was to measure the number of repeat computed tomography (CT) scans performed across an established health information exchange (HIE) in New York City. The long-term objective is to build an HIE-based duplicate CT alerting system to reduce potentially avoidable duplicate CTs. METHODS: This retrospective cohort analysis was based on HIE CT study records performed between March 2009 and July 2012. The number of CTs performed, the total number of patients receiving CTs, and the hospital locations where CTs were performed for each unique patient were calculated. Using a previously described process established by one of the authors, hospital-specific proprietary CT codes were mapped to the Logical Observation Identifiers Names and Codes (LOINC(r)) standard terminology for inter-site comparison. The number of locations where there was a repeated CT performed with the same LOINC code was then calculated for each unique patient. RESULTS: There were 717 231 CTs performed on 349 321 patients. Of these patients, 339 821 had all of their imaging studies performed at a single location, accounting for 668 938 CTs. Of these, 9500 patients had 48 293 CTs performed at more than one location. Of these, 6284 patients had 24 978 CTs with the same LOINC code performed at multiple locations. The median time between studies with the same LOINC code was 232 days (range of 0 to 1227); however, 1327 were performed within 7 days and 5000 within 30 days. CONCLUSIONS: A small proportion (3%) of our cohort had CTs performed at more than one location, however this represents a large number of scans (48 293). A noteworthy portion of these CTs (51.7%) shared the same LOINC code and may represent potentially avoidable studies, especially those done within a short time frame. This represents an addressable issue, and future HIE-based alerts could be utilized to reduce potentially avoidable CT scans. PMID- 27178987 TI - Update on FGF23 and Klotho signaling. AB - Fibroblast growth factor-23 (FGF23) is a bone-derived hormone known to suppress phosphate reabsorption and vitamin D hormone production in the kidney. Klotho was originally discovered as an anti-aging factor, but the functional role of Klotho is still a controversial issue. Three major functions have been proposed, a hormonal function of soluble Klotho, an enzymatic function as glycosidase, and the function as an obligatory co-receptor for FGF23 signaling. The purpose of this review is to highlight the recent advances in the area of FGF23 and Klotho signaling in the kidney, in the parathyroid gland, in the cardiovascular system, in bone, and in the central nervous system. During recent years, major new functions of FGF23 and Klotho have been discovered in these organ systems. Based on these novel findings, FGF23 has emerged as a pleiotropic endocrine and auto /paracrine factor influencing not only mineral metabolism but also cardiovascular function. PMID- 27178988 TI - Exploring human glycosylation for better therapies. AB - Glycosylation of lipids and proteins is not encoded by genes directly and depends on many factors including the origin of cell-lines, differential expression of carbohydrate enzymes and availability of substrates, as well as environmental conditions. Individual cells from different tissues produce each glycoprotein as heterogeneous mixtures of glycoforms with distinct biological activities in response to different conditions and disease states. As the result, the study of glycosylation could not rely purely on biochemical methods; instead it requires a multidisciplinary approach utilizing a variety of methods including genetic manipulation and glycosylation pathway engineering, structural and functional proteomic analysis, chemical and enzymatic synthesis, development of glycosylation probes and glycan microarrays. This review highlights recent progress and demonstrates how the availability of structure-defined oligosaccharides enables development of new and improved therapies, such as therapeutic homogeneous antibodies and carbohydrate-based vaccines against cancer. PMID- 27178989 TI - Efficacy of the RemoweLL cardiotomy reservoir for fat and leucocyte removal from shed mediastinal blood: a randomized controlled trial. AB - INTRODUCTION: Re-transfusion of lipid particles and activated leucocytes with shed mediastinal blood (SMB) can aggravate cardiopulmonary bypass-associated inflammation and increase the embolic load. This study evaluated the fat and leucocyte removal capacity of the RemoweLL cardiotomy reservoir. METHODS: Forty five patients undergoing elective on-pump cardiac surgery were randomly allocated to filtration of SMB using the RemoweLL or the Admiral cardiotomy reservoir. The primary outcome was a drop in leucocytes and lipid particles obtained with the two filters. The effect of the filters on other blood cells and inflammatory mediators, such as myeloperoxidase (MPO), was also assessed. RESULTS: The RemoweLL cardiotomy filter removed 16.5% of the leucocytes (p<0.001) while no significant removal of leucocytes was observed with the Admiral (p=0.48). The percentage reductions in lipid particles were similar in the two groups (26% vs 23%, p=0.2). Both filters similarly affected the level of MPO (p=0.71). CONCLUSION: The RemoweLL filter more effectively removed leucocytes from SMB than the Admiral. It offered no advantage in terms of lipid particle clearance. PMID- 27178990 TI - Similarity of coagulation and inflammation despite different surgical revascularization strategies - a prospective randomized trial. AB - BACKGROUND: Supposedly, minimized extracorporeal circulation or off-pump revascularization as alternatives to conventional extracorporeal circulation (ONCAB) reduce inflammation and coagulation disturbances. METHODS: One hundred and twenty coronary artery bypass graft (CABG) patients were prospectively randomized for three surgical techniques. Coagulation and inflammation markers were measured up to 72 hours postoperatively. RESULTS: Coagulation factors I, II, V, X, antithrombin III and C-reactive protein did not differ perioperatively between the groups and increased, as did several other markers, 12 to 72 hours postoperatively. Compared to its alternatives, ONCAB showed the most obvious transient increase in thrombin-antithrombin complexes (p<0.0001), D-dimers (p=0.0059), tissue factor pathway inhibitor (p=0.0005), factor VIII (p=0.0041) and tumor necrosis factor alpha (p=0.0300) during the operation and up to 12 hours postoperatively. Furthermore, ONCAB generated lower leukocyte and platelet counts and higher values of soluble P-selectin and soluble intercellular adhesion molecule 1 at some time points. CONCLUSIONS: With similarity in pivot coagulation factors, a specific detrimental influence of ONCAB on common coagulation pathways was excluded. Higher perioperative concentrations of products from the coagulation cascade most likely indicate activation of pericardial blood - recirculated only in ONCAB. Furthermore, with only temporary differences in markers of inflammation, the alternatives to ONCAB altogether were without advantage at 72 hours postoperatively. In the general answer to surgical trauma, the part of modern extracorporeal circulation is possibly overestimated.The study is registered at the German Clinical Trial Registry. Registration number DRKS00007580. URL: https://drks-neu.uniklinik-freiburg.de/drks_web/ URL: http://apps.who.int/trialsearch/. PMID- 27178991 TI - Extracorporeal membrane oxygenation after intravenous injection of paraffin oil. AB - We present a rare cause of acute respiratory distress syndrome (ARDS) due to an accidental intravascular injection of paraffin oil. While there is no specific therapy, we decided to support the patient with veno-venous extracorporeal membrane oxygenation (V-V ECMO) to allow the ARDS to resolve. A previously healthy 30-year-old man was admitted to the Emergency Department with acute onset respiratory distress following an injection with paraffin oil for cosmetic purposes. In 36 hours, the patient developed severe ARDS and respiratory support with V-V ECMO was initiated. The patient was successfully weaned from ECMO on day 11 and was discharged from hospital in full recovery. PMID- 27178992 TI - Detecting multi-way epistasis in family-based association studies. AB - The era of genome-wide association studies (GWAS) has led to the discovery of numerous genetic variants associated with disease. Better understanding of whether these or other variants interact leading to differential risk compared with individual marker effects will increase our understanding of the genetic architecture of disease, which may be investigated using the family-based study design. We present M-TDT (the multi-locus transmission disequilibrium test), a tool for detecting family-based multi-locus multi-allelic effects for qualitative or quantitative traits, extended from the original transmission disequilibrium test (TDT). Tests to handle the comparison between additive and epistatic models, lack of independence between markers and multiple offspring are described. Performance of M-TDT is compared with a multifactor dimensionality reduction (MDR) approach designed for investigating families in the hypothesis-free genome wide setting (the multifactor dimensionality reduction pedigree disequilibrium test, MDR-PDT). Other methods derived from the TDT or MDR to investigate genetic interaction in the family-based design are also discussed. The case of three independent biallelic loci is illustrated using simulations for one- to three locus alternative hypotheses. M-TDT identified joint-locus effects and distinguished effectively between additive and epistatic models. We showed a practical example of M-TDT based on three genes already known to be implicated in malaria susceptibility. Our findings demonstrate the value of M-TDT in a hypothesis-driven context to test for multi-way epistasis underlying common disease etiology, whereas MDR-PDT-based methods are more appropriate in a hypothesis-free genome-wide setting. PMID- 27178993 TI - MIRU-VNTR genotype diversity and indications of homoplasy in M. avium strains isolated from humans and slaughter pigs in Latvia. AB - Diseases which are caused by non-tuberculous mycobacteria (NTM) are an increasing problem in the developed countries. In Latvia, one of the most clinically important members of NTM is Mycobacterium avium (M. avium), an opportunistic pathogen which has been isolated from several lung disease patients and tissue samples of slaughter pigs. This study was designed to characterize the genetic diversity of the M. avium isolates in Latvia and to compare the distribution of genotypic patterns among humans and pigs. Eleven (Hall and Salipante, 2010) clinical M. avium samples, isolated from patients of Center of Tuberculosis and Lung Diseases (years 2003-2010), and 32 isolates from pig necrotic mesenterial lymph nodes in different regions (years 2003-2007) were analyzed. The majority (42 of 43) of samples were identified as M. avium subsp. hominissuis; one porcine isolate belonged to M. avium subsp. avium. MIRU-VNTR genotyping revealed 13 distinct genotypes, among which nine genotype patterns, including M. avium subsp. avium isolate, were newly identified. IS1245 RFLP fingerprinting of 25 M. avium subsp. hominissuis samples yielded 17 different IS1245 RFLP patterns, allowing an efficient discrimination of isolates. Clusters of identical RFLP profiles were observed within host species, geographical locations and time frame of several years. Additional in silico analysis on simulated MIRU-VNTR genotype population datasets showed that the MIRU-VNTR pattern similarity could partly arise due to probabilistic increase of acquiring homoplasy among subpopulations, thus the similar MIRU-VNTR profiles of M. avium strains even in close geographical proximity should be interpreted with caution. PMID- 27178994 TI - Untended wounds: Non-suicidal self-injury in adults with autism spectrum disorder. AB - Recent studies have examined non-suicidal self-injury in community and clinical samples, but there is no published research on non-suicidal self-injury in individuals with autism spectrum disorder. This lack of research is surprising, since individuals with autism spectrum disorder have high rates of risk factors for non-suicidal self-injury, including depression and poor emotion regulation skills. Using an online survey, we examined non-suicidal self-injury methods, frequency, severity, functions, and initial motivations in adults with autism spectrum disorder ( n = 42). We also compared their non-suicidal self-injury characteristics to those of a gender-matched group of adults without autism spectrum disorder ( n = 42). Of the participants with autism spectrum disorder, 50% reported a history of non-suicidal self-injury. This proportion is higher than non-suicidal self-injury rates previously reported for college students, adult community samples, and adolescents with autism spectrum disorder, which suggests that adults with autism spectrum disorder have increased risk for engaging in non-suicidal self-injury. Women with autism spectrum disorder were significantly more likely to endorse non-suicidal self-injury, relative to men with autism spectrum disorder. A history of non-suicidal self-injury was not related to current depression or emotion dysregulation for the participants with autism spectrum disorder. Non-suicidal self-injury characteristics among the adults with autism spectrum disorder were similar to non-suicidal self-injury in adults without autism spectrum disorder. These preliminary findings highlight the need for increased awareness and further research about non-suicidal self-injury within autism spectrum disorder. PMID- 27178995 TI - Clinical outcomes of behavioral treatments for elopement in individuals with autism spectrum disorder and other developmental disabilities. AB - The external validity of behavioral treatments for elopement (i.e. leaving supervision without permission) remains unclear because studies to date include only small samples ( n = 1-3). This study quantified the overall effectiveness of behavioral treatments for elopement by retrospectively examining treatment data from all patients seen for the treatment of elopement at an intensive day treatment clinic ( n = 11), irrespective of treatment success. Reductions in elopement from baseline to the final treatment for each participant demonstrate that behavioral intervention is a highly effective treatment for elopement, as determined by the large effect size (Cohen's d = 1.18). PMID- 27178996 TI - Parent-reported patterns of loss and gain in communication in 1- to 2-year-old children are not unique to autism spectrum disorder. AB - We compared loss and gain in communication from 1 to 2 years in children later diagnosed with autism spectrum disorder (n = 41), language impairment (n = 110) and in children with typical language development at 7 years (n = 831). Participants were selected from a prospective population cohort study of child language (the Early Language in Victoria Study). Parent-completed communication tools were used. As a group, children with autism spectrum disorder demonstrated slower median skill gain, with an increasing gap between trajectories compared to children with typical development and language impairment. A proportion from all groups lost skills in at least one domain (autism spectrum disorder (41%), language impairment (30%), typical development (26%)), with more children with autism spectrum disorder losing skills in more than one domain (autism spectrum disorder (47%), language impairment (15%, p = 0.0003), typical development (16%, p < 0.001)). Loss was most common for all groups in the domain of 'emotion and eye gaze' but with a higher proportion for children with autism spectrum disorder (27%; language impairment (12%, p = 0.03), typical development (14%, p = 0.03)). A higher proportion of children with autism spectrum disorder also lost skills in gesture (p = 0.01), sounds (p = 0.009) and understanding (p = 0.004) compared to children with typical development but not with language impairment. These findings add to our understanding of early communication development and highlight that loss is not unique to autism spectrum disorder. PMID- 27178997 TI - Trajectories and correlates of special education supports for youth with autism spectrum disorder and psychiatric comparisons. AB - Relatively little is known about patterns of school-based supportive services for youth with autism spectrum disorder. This study describes these supportive services and their correlates, both cross-sectionally and retrospectively, in a large sample ( N = 283) of 6- to 18- year-old youth. To assess whether special education designation and classroom placement patterns were peculiar to autism spectrum disorder, we also conducted analyses comparing youth with autism spectrum disorder to those with other psychiatric diagnoses ( N = 1088). In higher grades, the relative quantity of three common supportive services received by youth with autism spectrum disorder decreased, while total supportive service quantity remained stable over time. Youth with autism spectrum disorder were more likely to receive a special education designation and were placed in less inclusive classroom settings than youth with other psychiatric diagnoses. These findings suggest that as youth with autism spectrum disorder reach higher grades, changes in service provision occur in terms of both time and quantity. PMID- 27178999 TI - Concepts for communication about risk in dementia care: A review of the literature. AB - Communication about risk is central to decisions in dementia care. This review synthesises research on risk concepts and communication in dementia. Twelve bibliographic databases and one online search engine were searched up to February 2016. Reference lists of two related literature reviews were used. Thirty-four articles were identified that focused on risk concepts; two articles related to risk communication. Concepts were often socially constructed, and perceptions may differ from actual adverse outcomes. Perceptions of risk and thresholds of risk tolerance varied between individuals with dementia, carers and professionals. Individuals with dementia were found to behave differently from controls when making decisions involving risk information in experimental settings. Cognitive impairment was also associated with lower health numeracy. These findings highlight the importance of communication between stakeholders when making decisions and of presenting information in an appropriate way to support informed and positive risk taking. Research is required on risk communication in dementia. PMID- 27178998 TI - Social analogical reasoning in school-aged children with autism spectrum disorder and typically developing peers. AB - Analogical reasoning is an important mechanism for social cognition in typically developing children, and recent evidence suggests that some forms of analogical reasoning may be preserved in autism spectrum disorder. An unanswered question is whether children with autism spectrum disorder can apply analogical reasoning to social information. In all, 92 children with autism spectrum disorder completed a social content analogical reasoning task presented via photographs of real-world social interactions. Autism spectrum disorder participants exhibited performance that was well above chance and was not significantly worse than age- and intelligence quotient-matched typically developing children. Investigating the relationship of social content analogical reasoning performance to age in this cross-sectional dataset indicated similar developmental trajectories in the autism spectrum disorder and typically developing children groups. These findings provide new support for intact analogical reasoning in autism spectrum disorder and have theoretical implications for analogy as a metacognitive skill that may be at least partially dissociable from general deficits in processing social content. As an initial study of social analogical reasoning in children with autism spectrum disorder, this study focused on a basic research question with limited ecological validity. Evidence that children with autism spectrum disorder can apply analogical reasoning ability to social content may have long-range applied implications for exploring how this capacity might be channeled to improve social cognition in daily life. PMID- 27179000 TI - 'Theatre as an eye-opener': How theatre may contribute to knowledge about living close to persons with dementia. AB - The aim of the study was to show how theatre may yield insight into living close to persons with dementia. Six focus group interviews with health providers and close relatives were conducted. The informants, recruited by the local dementia associations and nursing homes in three Norwegian towns, were invited to see the theatre play Our Wonderful World. Further, they were asked to send written reflections from during and after the play to the project group within one week. Transcripts from the interviews and reflection notes were analysed inspired by a phenomenological approach. After discussion and reflection on each member's preliminary themes, a common meaning of the informants' experiences were gained. Informants gave written informed consent and The Norwegian Social Sciences Data Services assessed the project. Data showed that the two groups of informants had different knowledge of the patients' earlier life and thoughts of the future. They became aware of how different they experienced their responsibility, and they expressed different attitudes as to how open one should be about the illness. Findings are summarised in four themes: Bright memories and sombre views of the future, Life responsibility versus professional responsibility and Shielding versus openness. The drama creates emotional engagement that enabled the informants to transcend their personal experiences and gain new knowledge. PMID- 27179001 TI - Study partners perform essential tasks in dementia research and can experience burdens and benefits in this role. AB - Most studies that enroll individuals with dementia require a study partner for each participant. Study partners-usually family members-perform several key roles: accompanying the participant to visits, providing information about the participant, and assisting with procedures such as taking medication. Little is known, however, about their experiences when performing these roles. Dementia researchers and institutional review boards need to know these experiences because the study partner role is one key factor in a study's success. This prospective qualitative study, using up to three semi-structured interviews with 62 study partners involved in a range of dementia studies, documented their subjective experiences. Content analysis demonstrates that study partners perform a range of tasks-often within the context of being a caregiver-that enable cognitively impaired individuals to participate in dementia research. These tasks present study partners with unique burdens and benefits, some of which dementia researchers and institutional review boards can address. PMID- 27179002 TI - Missing covariates in competing risks analysis. AB - Studies often follow individuals until they fail from one of a number of competing failure types. One approach to analyzing such competing risks data involves modeling the cause-specific hazards as functions of baseline covariates. A common issue that arises in this context is missing values in covariates. In this setting, we first establish conditions under which complete case analysis (CCA) is valid. We then consider application of multiple imputation to handle missing covariate values, and extend the recently proposed substantive model compatible version of fully conditional specification (SMC-FCS) imputation to the competing risks setting. Through simulations and an illustrative data analysis, we compare CCA, SMC-FCS, and a recent proposal for imputing missing covariates in the competing risks setting. PMID- 27179003 TI - Introduction to the Special Issue: Interventions to Improve Children's Social and Emotional Functioning at School. AB - Identification of evidence-based practices for promotion of social and emotional functioning of children at school is important for their academic and social development. This introduction reviews information from this special issue focusing on evidence-based research to improve the social and emotional functioning of children in their classrooms and schools. An emphasis on reduction of negative behaviors and promotion of positive, prosocial behaviors is presented in manuscripts for this special issue. The articles in this issue may be grouped in terms of the tiered system or School-Wide Positive Behavior Interventions and Supports Framework into articles at the Tier I, II, and III levels. Tier I interventions support positive behaviors and reduce problem behaviors for all children in a classroom or school, as a type of primary prevention. In terms of secondary prevention, Tier II interventions are selected interventions that address problem behaviors of students at risk for poor functioning, who do not respond to Tier I interventions. Finally, Tier III interventions are used for those students with behavioral and emotional issues who do not respond to Tier II interventions, and students in this group are indicated for intervention at a tertiary care level. In summary, this special issue presents evidence-based knowledge from research at all three intervention levels that aim to promote children's social and emotional development in the school setting. PMID- 27179004 TI - A review of current surgical practice in the operative treatment of proximal humeral fractures: Does the PROFHER trial demonstrate a need for change? AB - OBJECTIVES: The PROximal Fracture of the Humerus: Evaluation by Randomisation (PROFHER) trial has recently demonstrated that surgery is non-superior to non operative treatment in the management of displaced proximal humeral fractures. The objective of this study was to assess current surgical practice in the context of the PROFHER trial in terms of patient demographics, injury characteristics and the nature of the surgical treatment. METHODS: A total of ten consecutive patients undergoing surgery for the treatment of a proximal humeral fracture from each of 11 United Kingdom hospitals were retrospectively identified over a 15 month period between January 2014 and March 2015. Data gathered for the 110 patients included patient demographics, injury characteristics, mode of surgical fixation, the grade of operating surgeon and the cost of the surgical implants. RESULTS: A majority of the patients were female (66%, 73 of 110). The mean patient age was 62 years (range 18 to 89). A majority of patients met the inclusion criteria for the PROFHER trial (75%, 83 of 110). Plate fixation was the most common mode of surgery (68%, 75 patients), followed by intramedullary fixation (12%, 13 patients), reverse shoulder arthroplasty (10%, 11 patients) and hemiarthroplasty (7%, eight patients). The consultant was either the primary operating surgeon or supervising the operating surgeon in a large majority of cases (91%, 100 patients). Implant costs for plate fixation were significantly less than both hemiarthroplasty (p < 0.05) and reverse shoulder arthroplasty (p < 0.0001). Implant costs for intramedullary fixation were significantly less than plate fixation (p < 0.01), hemiarthroplasty (p < 0.0001) and reverse shoulder arthroplasty (p < 0.0001). CONCLUSIONS: Our study has shown that the majority of a representative sample of patients currently undergoing surgical treatment for a proximal humeral fracture in these United Kingdom centres met the inclusion criteria for the PROFHER trial and that a proportion of these patients may, therefore, have been effectively managed non-operatively.Cite this article: Mr B. J. F. Dean. A review of current surgical practice in the operative treatment of proximal humeral fractures: Does the PROFHER trial demonstrate a need for change? Bone Joint Res 2016;5:178-184. DOI: 10.1302/2046-3758.55.2000596. PMID- 27179005 TI - Targeting methanogenesis with a nitrooxypropanol bullet. PMID- 27179006 TI - Moving forward in perceptual decision making. PMID- 27179007 TI - Molecular basis for differential light responses in Arabidopsis stems and leaves. PMID- 27179008 TI - Ecosystem impacts of climate extremes crucially depend on the timing. PMID- 27179009 TI - Food deprivation induces presynaptic plasticity in the autonomic nervous system. PMID- 27179010 TI - Registry of Youth Onset Diabetes in India (YDR): Rationale, Recruitment, and Current Status. AB - BACKGROUND: With the aim of addressing the relative scarcity of information on youth-onset diabetes in India, the Indian Council of Medical Research (ICMR) decided to establish the Registry of People with Diabetes with Young Age at Onset (YDR) in 2006. The major objectives of YDR are to generate information on disease pattern or types of youth-onset diabetes including their geographical variations within India and to estimate the burden of diabetes complications. METHODS: YDR is an observational multicenter clinic based registry enlisting physician diagnosed diabetes in individuals below 25 years of age. Diabetes was classified using symptom based clinical criteria. YDR data collection is coordinated through regional collaborating centers and their interacting reporting centers across India. A baseline and an annual follow-up proformas are used to obtain information on sociodemographic details, clinical profile, and anthropometric and laboratory measurements of the patients. RESULTS: In phase 1, the registry has enrolled 5546 patients, in which type 1 diabetes mellitus (T1DM) was the most prevalent (63.9%), followed by youth-onset type 2 diabetes mellitus (T2DM) (25.3%). CONCLUSION: This registry provides a unique opportunity to study the natural history of youth-onset diabetes in India. PMID- 27179011 TI - Diabetes Educators' Intended and Reported Use of Common Diabetes-Related Technologies: Discrepancies and Dissonance. AB - BACKGROUND: Technology provides adjuvant and/or alternative approaches to care and may promote self-care, communication, and engagement with health care services. Common recent technologies for diabetes include continuous subcutaneous insulin infusions (insulin pumps), continuous glucose monitoring systems, smartphone and tablet applications, and telehealth (video conferencing). This study reports Australian diabetes educators' intentions and reported professional use of these technologies for people with type 1 diabetes, and factors predictive of this. METHODS: An anonymous, web-based questionnaire based on the technology acceptance model was distributed to members of the Australian Diabetes Educators Association through their electronic newsletter. Exploratory factor analysis revealed a 5-factor solution comprising confidence and competence, improving clinical practice, preparation (intentions and training), ease of use, and subjective norms. Logistic regression analyses identified factors predicting intention and use of technology. RESULTS: Respondents (n = 228) had high intentions to use technology. The majority reported using continuous subcutaneous insulin infusions, continuous glucose monitoring systems, and applications with patients, but usage was occasional. Confidence and competence independently predicted both intentions and use of all 4 technologies. Preparation (intentions and training) independently predicted use of each technology also. CONCLUSIONS: Discrepancies and dissonance appear between diabetes educators' intentions and behavior (intentions to use and reported technology use). Intentions were higher than current use, which was relatively low and not likely to provide significant support to people with type 1 diabetes for disease management, communication, and engagement with health care services. Continuing education and experiential learning may be key in supporting diabetes educators to align their intentions with their practice. PMID- 27179012 TI - Postmarket Approval Surveillance of a Low Acquisition Cost Blood Glucose Monitoring System: Assessment of the Accuracy Following ISO 15197:2013. PMID- 27179013 TI - Fatigue and Oxidative Stress in Children Undergoing Leukemia Treatment. AB - Fatigue is a frequent and distressing symptom in children undergoing leukemia treatment; however, little is known about factors influencing this symptom. Antioxidants such as glutathione can decrease symptom severity in adult oncology patients, but no study has evaluated antioxidants' effects on symptoms in pediatric oncology patients. This study describes fatigue patterns and associations of fatigue with antioxidants represented by reduced glutathione (GSH) and the reduced/oxidized glutathione (GSH/GSSG) ratio among children receiving leukemia treatment. A repeated measures design assessed fatigue and antioxidants among 38 children from two large U.S. cancer centers. Fatigue was assessed among school-age children and by parent proxy among young children. Antioxidants (GSH and GSH/GSSG ratio) were assessed from cerebrospinal fluid at four phases during leukemia treatment. Young children had a steady decline of fatigue from the end of induction treatment through the continuation phase of treatment, but no significant changes were noted among the school-age children. Mean antioxidant scores varied slightly over time; however, the GSH/GSSG ratios in these children were significantly lower than the normal ratio. Mean GSH/GSSG ratios significantly correlated to fatigue scores of the school-age children during early phases of treatment. Children with low mean GSH/GSSG ratios demonstrated oxidative stress. The low ratios noted early in therapy were significantly correlated with higher fatigue scores during induction and postinduction treatment phases. This finding suggests that increased oxidative stress during the more intensive phases of therapy may explain the experience of fatigue children report. PMID- 27179014 TI - Association of the Genetic Polymorphisms RRM1 -756T>C and -269C>A With Cervical Neoplasia. AB - Cervical neoplasia is one of the most prevalent malignant neoplasms worldwide. Ribonucleotide reductase 1 (RRM1) is thought to play an essential role in modulating the development and progression of cervical neoplasia. Two novel genetic polymorphisms, RRM1 -756T>C and -269 C>A, are significantly correlated with RRM1 expression. Some epidemiological studies have demonstrated that genetic variants play a crucial role in susceptibility to cervical cancer. The present study aimed to identify the genetic polymorphisms RRM1 -756T>C and -269 C>A in patients with cervical neoplasia and healthy controls. In total, 493 subjects, comprising 324 healthy controls and 169 patients with cervical neoplasia, were enrolled for this study. The allelic discrimination of the RRM1 -756T>C (rs11030918) and -269C>A (rs12806698) polymorphisms was assessed using the ABI StepOneTM real-time polymerase chain reaction system and analyzed using Software Design Specification (SDS), Version 3.0, software with TaqMan assays. The risk of cervical cancer was examined, revealing adjusted odds ratios and 95% confidence intervals of 1.25 [0.51, 3.08] and 1.09 [0.43, 2.78] for individuals with CC alleles of RRM1 -756T>C and for individuals with AA alleles of RRM1 -269C>A genetic polymorphisms, respectively, compared to individuals with wild-type RRM1 genetic polymorphisms. No significant genetic interaction effect was observed in susceptibility to cervical neoplasia, and no association was found between genetic polymorphisms and clinical statuses of invasive cervical cancer. The genetic polymorphisms RRM1 -756T>C and -269C>A may not be a factor for susceptibility to cervical neoplasia. PMID- 27179015 TI - Efficacy and Safety of Fondaparinux in Patients With Suspected Heparin-Induced Thrombocytopenia. AB - OBJECTIVE: Heparin-induced thrombocytopenia (HIT) occurs in up to 5% of patients exposed to unfractionated heparin for 5 or more days. Direct thrombin inhibitors (DTIs) are currently the only Food and Drug Administration (FDA)-approved agents for the treatment of HIT. The purpose of this study is to determine whether fondaparinux is an appropriate first-line alternative anticoagulant in patients with suspected or confirmed HIT. METHODS: A retrospective study was conducted by identifying all patients who received a DTI or fondaparinux during a 5 year period, August 2009-August 2014. Patients were included if they had a HIT panel/serotonin-release assay analysis (regardless of the result) and were initiated on a DTI or fondaparinux for alternative anticoagulation. The primary outcome was new, recurrent, or progressive thromboembolic event. Secondary outcomes included bleeding events, platelet count recovery, and hospital stay. RESULTS: A total of 1022 patients were evaluated, and 47 patients met the inclusion criteria. Twelve patients were HIT positive and 35 were HIT negative. Seven (14.9%) of the 47 patients experienced a new thrombosis, none of whom were on fondaparinux only (FONDA). There were 4 new minor bleeds, with 1 bleed as a result of being on fondaparinux. FONDA treatment resulted in a slightly shorter median duration of hospital stay compared to the DTI-only group and the DTI followed by fondaparinux group. There is a potential for cost savings with fondaparinux due to the ease of administration and availability to be given in the outpatient setting. CONCLUSION: In this small retrospective review, fondaparinux appeared similarly efficacious and safe compared to DTIs for the treatment of suspected HIT. PMID- 27179016 TI - Two new blood tests will help doctors rule out pre-eclampsia, says NICE. PMID- 27179017 TI - Inequalities in a National Health Care System From the Perspective of Social Workers in Israel. AB - This study explores social workers' perceptions of inequalities in Israel's national health care system. Unlike previous studies, which relied on patients' and practitioners' reports, it is based on interviews with 60 social workers in hospitals and ambulatory clinics. The findings show that although Israeli law provides for (almost) free, universal medical care, the treatment of persons lacking in money, education, and social affiliation may be compromised by difficulties in paying for medications, treatments, and travel to and from hospital; by difficulties in understanding doctors' instructions; and by reluctance to ask questions. Most doctors tend to focus exclusively on patients' medical needs, seem to lack sympathy with less educated patients, have little understanding of the life circumstances that impinge on their compliance, and make little effort to speak to them in the language they can understand. Practical suggestions are made with regard to the need to turn doctors' attention to their patients' non-medical needs. PMID- 27179018 TI - Distributed Cognition in Cancer Treatment Decision Making: An Application of the DECIDE Decision-Making Styles Typology. AB - Distributed cognition occurs when cognitive and affective schemas are shared between two or more people during interpersonal discussion. Although extant research focuses on distributed cognition in decision making between health care providers and patients, studies show that caregivers are also highly influential in the treatment decisions of patients. However, there are little empirical data describing how and when families exert influence. The current article addresses this gap by examining decisional support in the context of cancer randomized clinical trial (RCT) decision making. Data are drawn from in-depth interviews with rural, Appalachian cancer patients ( N = 46). Analysis of transcript data yielded empirical support for four distinct models of health decision making. The implications of these findings for developing interventions to improve the quality of treatment decision making and overall well-being are discussed. PMID- 27179020 TI - Seeking Help From Everyone and No-One: Conceptualizing the Online Help-Seeking Process Among Adolescent Males. AB - Online help-seeking is an emerging trend within the 21st century. Yet, despite some movement toward developing online services, little is known about how young people locate, access, and receive support online. This study aims to conceptualize the process of online help-seeking among adolescent males. Modified photo-elicitation techniques were employed within eight semi-structured focus group sessions with adolescent males aged 14 to 15 years (n = 56) across seven schools in Northern Ireland. Thematic analyses were conducted within an ontological framework of critical realism and an epistemological framework of contextualism. Informal online help-seeking pathways increased opportunity for social support and reduced stigma but also included loss of control and reduced anonymity. Formal pathways offered increased anonymity but concerns were raised regarding participants' ability to locate and appraise the quality of information online. A conceptual model of online help-seeking has been developed to highlight the key help-seeking pathways taken by adolescent males. PMID- 27179019 TI - Illness Experiences, Collective Decisions, and the Therapeutic Encounter in Indian Oncology. AB - Social science scholarship on cancer has been almost exclusively focused on Organization for Economic Cooperation and Development (OECD) countries, despite a significant epidemiological transition taking place in many non-OECD contexts, with cancer emerging as a prominent, and strongly feared, illness experience. With cancer gaining an increasingly high profile in India, there is an urgent need to explore how experiences of cancer may be socially and culturally embedded, and in turn, how localized practices may shape the therapeutic encounter. Here, drawing on interviews with 40 people living with cancer in Hyderabad, India, we focus on some specific components of their therapeutic journeys, including diagnostic and prognostic disclosure, collective versus individual decision making, the dynamics of medical authority, and the reception of cancer within their social milieu. These participants' accounts provide insight into a range of cultural sensibilities around illness and care, and reinforce the importance of understanding the cultural inflections of communication, decisions, and illness experiences. PMID- 27179021 TI - "What Do They Really Mean by Partnerships?" Questioning the Unquestionable Good in Ethics Guidelines Promoting Community Engagement in Indigenous Health Research. AB - Academics and community members collaborated in research to examine how best to apply ethics guidelines for research involving Indigenous communities in a community with complex and multiple political and cultural jurisdictions. We examined issues of NunatuKavut (Southern Inuit) authority and representation in relation to governance of research in a context where community identity is complex and shifting, and new provincial legislation mandates centralized ethics review. We scrutinize the taken-for-granted assumption of research ethics that community engagement is an unquestionable "good." We examine the question of whether and how research ethics guidelines and associated assumptions about the value of community engagement may be grounded in, and inadvertently reinforce, ongoing colonialist relations of power. We present findings that community engagement-if done uncritically and in service to ethics guidelines rather than in service to ethical research-can itself cause harm by leading to community fatigue, undermining the community's ability to be effectively involved in the research, and restricting the community's ability to have oversight and control over research. We conclude by suggesting that the laudable goal of engaging communities in research requires careful reflection on the appropriate use of resources to operationalize meaningful collaboration. PMID- 27179022 TI - Belonging and Mental Wellbeing Among a Rural Indian-Canadian Diaspora: Navigating Tensions in "Finding a Space of Our Own". AB - Belonging is linked to a variety of positive health outcomes. Yet this relationship is not well understood, particularly among rural immigrant diasporas. In this article, we explore the experiences of community belonging and wellbeing among a rural Indian-Canadian diaspora in the Interior of British Columbia, Canada, our central research questions being, "What are the experiences of belonging in this community? How does a sense of belonging (or lack of) shape mental health and wellbeing among local residents?" Using a situational analysis research approach, our findings indicate that local residents must navigate several tensions within an overarching reality of finding a space of our own. Such tensions reveal contradictory experiences of tight-knitedness, context informed notions of cultural continuity, access/acceptability barriers, particularly in relation to rural agricultural living, and competing expectations of "small town" life. Such tensions can begin to be addressed through creative service provision, collaborative decision making, and diversity-informed program planning. PMID- 27179023 TI - Toward a Better Understanding of Patient Health Literacy: A Focus on the Skills Patients Need to Find Health Information. AB - While many health literacy assessments exist, this area of research lacks an instrument that isolates and reflects the four components driving this concept (abilities to find, understand, use, and communicate about health information). The purpose of this study was to determine what abilities comprise the first component, how a patient finds health information. Low ( n = 13) and adequate ( n = 14) health literacy patients, and health professionals ( n = 10) described their experiences when looking for health information and the skills they employed to complete these tasks. Major skills/themes elicited included knowing when to search, credibility assessments, finding text and numerical information, interpersonal seeking, technology and online search, and spatial navigation. Findings from this study suggest that each of the dimensions included in the definition of health literacy warrants specific attention and assessment. Given identification of the skills comprising each dimension, interventions targeting deficits across health literacy dimensions could be developed to improve patient health. PMID- 27179024 TI - Sen1, the yeast homolog of human senataxin, plays a more direct role than Rad26 in transcription coupled DNA repair. AB - Rad26, a DNA dependent ATPase that is homologous to human CSB, has been well known to play an important role in transcription coupled DNA repair (TCR) in the yeast Saccharomyces cerevisiae Sen1, a DNA/RNA helicase that is essential for yeast cell viability and homologous to human senataxin, has been known to be required for transcriptional termination of short noncoding RNA genes and for a fail-safe transcriptional termination mechanism of protein-coding genes. Sen1 has also been shown to protect the yeast genome from transcription-associated recombination by resolving RNA:DNA hybrids naturally formed during transcription. Here, we show that the N-terminal non-essential region of Sen1 plays an important role in TCR, whereas the C-terminal nonessential region and the helicase activity of Sen1 are largely dispensable for the repair. Unlike Rad26, which becomes completely dispensable for TCR in cells lacking the TCR repressor Spt4, Sen1 is still required for efficient TCR in the absence of Spt4. Also unlike Rad26, which is important for repair at many but not all damaged sites in the transcribed strand of a gene, Sen1 is required for efficient repair at essentially all the damaged sites. Our results indicate that Sen1 plays a more direct role than Rad26 in TCR. PMID- 27179025 TI - Allosteric communication between DNA-binding and light-responsive domains of diatom class I aureochromes. AB - The modular architecture of aureochrome blue light receptors, found in several algal groups including diatoms, is unique by having the LOV-type photoreceptor domain fused to the C-terminus of its putative effector, an N-terminal DNA binding bZIP module. The structural and functional understanding of aureochromes' light-dependent signaling mechanism is limited, despite their promise as an optogenetic tool. We show that class I aureochromes 1a and 1c from the diatom Phaeodactylum tricornutum are regulated in a light-independent circadian rhythm. These aureochromes are capable to form functional homo- and heterodimers, which recognize the ACGT core sequence within the canonical 'aureo box', TGACGT, in a light-independent manner. The bZIP domain holds a more folded and less flexible but extended conformation in the duplex DNA-bound state. FT-IR spectroscopy in the absence and the presence of DNA shows light-dependent helix unfolding in the LOV domain, which leads to conformational changes in the bZIP region. The solution structure of DNA bound to aureochrome points to a tilted orientation that was further validated by molecular dynamics simulations. We propose that aureochrome signaling relies on an allosteric pathway from LOV to bZIP that results in conformational changes near the bZIP-DNA interface without major effects on the binding affinity. PMID- 27179027 TI - TSCAN: Pseudo-time reconstruction and evaluation in single-cell RNA-seq analysis. AB - When analyzing single-cell RNA-seq data, constructing a pseudo-temporal path to order cells based on the gradual transition of their transcriptomes is a useful way to study gene expression dynamics in a heterogeneous cell population. Currently, a limited number of computational tools are available for this task, and quantitative methods for comparing different tools are lacking. Tools for Single Cell Analysis (TSCAN) is a software tool developed to better support in silico pseudo-Time reconstruction in Single-Cell RNA-seq ANalysis. TSCAN uses a cluster-based minimum spanning tree (MST) approach to order cells. Cells are first grouped into clusters and an MST is then constructed to connect cluster centers. Pseudo-time is obtained by projecting each cell onto the tree, and the ordered sequence of cells can be used to study dynamic changes of gene expression along the pseudo-time. Clustering cells before MST construction reduces the complexity of the tree space. This often leads to improved cell ordering. It also allows users to conveniently adjust the ordering based on prior knowledge. TSCAN has a graphical user interface (GUI) to support data visualization and user interaction. Furthermore, quantitative measures are developed to objectively evaluate and compare different pseudo-time reconstruction methods. TSCAN is available at https://github.com/zji90/TSCAN and as a Bioconductor package. PMID- 27179026 TI - An epigenetic switch regulates de novo DNA methylation at a subset of pluripotency gene enhancers during embryonic stem cell differentiation. AB - Coordinated regulation of gene expression that involves activation of lineage specific genes and repression of pluripotency genes drives differentiation of embryonic stem cells (ESC). For complete repression of pluripotency genes during ESC differentiation, chromatin at their enhancers is silenced by the activity of the Lsd1-Mi2/NuRD complex. The mechanism/s that regulate DNA methylation at these enhancers are largely unknown. Here, we investigated the affect of the Lsd1 Mi2/NuRD complex on the dynamic regulatory switch that induces the local interaction of histone tails with the Dnmt3 ATRX-DNMT3-DNMT3L (ADD) domain, thus promoting DNA methylation at the enhancers of a subset of pluripotency genes. This is supported by previous structural studies showing a specific interaction between Dnmt3-ADD domain with H3K4 unmethylated histone tails that is disrupted by histone H3K4 methylation and histone acetylation. Our data suggest that Dnmt3a activity is triggered by Lsd1-Mi2/NuRD-mediated histone deacetylation and demethylation at these pluripotency gene enhancers when they are inactivated during mouse ESC differentiation. Using Dnmt3 knockout ESCs and the inhibitors of Lsd1 and p300 histone modifying enzymes during differentiation of E14Tg2A and ZHBTc4 ESCs, our study systematically reveals this mechanism and establishes that Dnmt3a is both reader and effector of the epigenetic state at these target sites. PMID- 27179028 TI - The SNF2 family ATPase LSH promotes cell-autonomous de novo DNA methylation in somatic cells. AB - Methylation of DNA at carbon 5 of cytosine is essential for mammalian development and implicated in transcriptional repression of genes and transposons. New patterns of DNA methylation characteristic of lineage-committed cells are established at the exit from pluripotency by de novo DNA methyltransferases enzymes, DNMT3A and DNMT3B, which are regulated by developmental signaling and require access to chromatin-organized DNA. Whether or not the capacity for de novo DNA methylation of developmentally regulated loci is preserved in differentiated somatic cells and can occur in the absence of exogenous signals is currently unknown. Here, we demonstrate that fibroblasts derived from chromatin remodeling ATPase LSH (HELLS)-null mouse embryos, which lack DNA methylation from centromeric repeats, transposons and a number of gene promoters, are capable of reestablishing DNA methylation and silencing of misregulated genes upon re expression of LSH. We also show that the ability of LSH to bind ATP and the cellular concentration of DNMT3B are critical for cell-autonomous de novo DNA methylation in somatic cells. These data suggest the existence of cellular memory that persists in differentiated cells through many cell generations and changes in transcriptional state. PMID- 27179030 TI - DeAnnIso: a tool for online detection and annotation of isomiRs from small RNA sequencing data. AB - Small RNA (sRNA) Sequencing technology has revealed that microRNAs (miRNAs) are capable of exhibiting frequent variations from their canonical sequences, generating multiple variants: the isoforms of miRNAs (isomiRs). However, integrated tool to precisely detect and systematically annotate isomiRs from sRNA sequencing data is still in great demand. Here, we present an online tool, DeAnnIso (Detection and Annotation of IsomiRs from sRNA sequencing data). DeAnnIso can detect all the isomiRs in an uploaded sample, and can extract the differentially expressing isomiRs from paired or multiple samples. Once the isomiRs detection is accomplished, detailed annotation information, including isomiRs expression, isomiRs classification, SNPs in miRNAs and tissue specific isomiR expression are provided to users. Furthermore, DeAnnIso provides a comprehensive module of target analysis and enrichment analysis for the selected isomiRs. Taken together, DeAnnIso is convenient for users to screen for isomiRs of their interest and useful for further functional studies. The server is implemented in PHP + Perl + R and available to all users for free at: http://mcg.ustc.edu.cn/bsc/deanniso/ and http://mcg2.ustc.edu.cn/bsc/deanniso/. PMID- 27179029 TI - FANCJ is essential to maintain microsatellite structure genome-wide during replication stress. AB - Microsatellite DNAs that form non-B structures are implicated in replication fork stalling, DNA double strand breaks (DSBs) and human disease. Fanconi anemia (FA) is an inherited disorder in which mutations in at least nineteen genes are responsible for the phenotypes of genome instability and cancer predisposition. FA pathway proteins are active in the resolution of non-B DNA structures including interstrand crosslinks, G quadruplexes and DNA triplexes. In FANCJ helicase depleted cells, we show that hydroxyurea or aphidicolin treatment leads to loss of microsatellite polymerase chain reaction signals and to chromosome recombination at an ectopic hairpin forming CTG/CAG repeat in the HeLa genome. Moreover, diverse endogenous microsatellite signals were also lost upon replication stress after FANCJ depletion, and in FANCJ null patient cells. The phenotype of microsatellite signal instability is specific for FANCJ apart from the intact FA pathway, and is consistent with DSBs at microsatellites genome-wide in FANCJ depleted cells following replication stress. PMID- 27179034 TI - Celebrating 35 Years of the AJNR: May 1981 edition. PMID- 27179031 TI - tRF2Cancer: A web server to detect tRNA-derived small RNA fragments (tRFs) and their expression in multiple cancers. AB - tRNA-derived small RNA fragments (tRFs) are one class of small non-coding RNAs derived from transfer RNAs (tRNAs). tRFs play important roles in cellular processes and are involved in multiple cancers. High-throughput small RNA (sRNA) sequencing experiments can detect all the cellular expressed sRNAs, including tRFs. However, distinguishing genuine tRFs from RNA fragments generated by random degradation remains a major challenge. In this study, we developed an integrated web-based computing system, tRF2Cancer, to accurately identify tRFs from sRNA deep-sequencing data and evaluate their expression in multiple cancers. The binomial test was introduced to evaluate whether reads from a small RNA-seq data set represent tRFs or degraded fragments. A classification method was then used to annotate the types of tRFs based on their sites of origin in pre-tRNA or mature tRNA. We applied the pipeline to analyze 10 991 data sets from 32 types of cancers and identified thousands of expressed tRFs. A tool called 'tRFinCancer' was developed to facilitate the users to inspect the expression of tRFs across different types of cancers. Another tool called 'tRFBrowser' shows both the sites of origin and the distribution of chemical modification sites in tRFs on their source tRNA. The tRF2Cancer web server is available at http://rna.sysu.edu.cn/tRFfinder/. PMID- 27179035 TI - Antihepatocellular Carcinoma Potential of Tetramethylpyrazine Induces Cell Cycle Modulation and Mitochondrial-Dependent Apoptosis: Regulation of p53 Signaling Pathway in HepG2 Cells In Vitro. AB - Tetramethylpyrazine (TMP) was originally isolated from a traditional Chinese herbal medicine, Ligusticum chuanxiong In the present study, TMP exhibits potent antitumor activities in vitro. However, the molecular mechanisms remain to be defined. Hence, this study aims to investigate the antiproliferative and apoptotic effects of TMP on HepG2 and elucidate the underlying mechanisms. Analyses using Cell Counting Kit-8 and real-time cell analyzer indicated that TMP significantly inhibited HepG2 cell proliferation. We also observed that TMP induced cell cycle arrest at the G0/G1 checkpoint and apoptosis, using flow cytometry and high-content screening. Furthermore, our results predicted that TMP could directly decrease mitochondrial membrane potential (Deltapsim), increase the release of cytochrome c, and increase caspase activation, indicating that mitochondrial pathway apoptosis could be the mechanism for TMP within HepG2 cells. Moreover, TMP altered expression of p53 and the Bcl-2/Bax protein ratio, which revealed that TMP induced cell cycle arrest and caspase-dependent mitochondrial apoptosis in HepG2 cells in vitro. These studies provided mechanistic insights into the antitumor properties of TMP, which may be explored as a potential option for treatment of hepatocellular carcinoma. PMID- 27179036 TI - In Vivo Genetic Screens of Patient-Derived Tumors Revealed Unexpected Frailty of the Transformed Phenotype. AB - The identification of genes maintaining cancer growth is critical to our understanding of tumorigenesis. We report the first in vivo genetic screen of patient-derived tumors, using metastatic melanomas and targeting 236 chromatin genes by expression of specific shRNA libraries. Our screens revealed unprecedented numerosity of genes indispensable for tumor growth (~50% of tested genes) and unexpected functional heterogeneity among patients (<15% in common). Notably, these genes were not activated by somatic mutations in the same patients and are therefore distinguished from mutated cancer driver genes. We analyzed underlying molecular mechanisms of one of the identified genes, the Histone lysine N-methyltransferase KMT2D, and showed that it promotes tumorigenesis by dysregulating a subset of transcriptional enhancers and target genes involved in cell migration. The assembly of enhancer genomic patterns by activated KMT2D was highly patient-specific, regardless of the identity of transcriptional targets, suggesting that KMT2D might be activated by distinct upstream signaling pathways. SIGNIFICANCE: Drug targeting of biologically relevant cancer-associated mutations is considered a critical strategy to control cancer growth. Our functional in vivo genetic screens of patient-derived tumors showed unprecedented numerosity and interpatient heterogeneity of genes that are essential for tumor growth, but not mutated, suggesting that multiple, patient-specific signaling pathways are activated in tumors. Cancer Discov; 6(6); 650-63. (c)2016 AACR.This article is highlighted in the In This Issue feature, p. 561. PMID- 27179045 TI - The importance of measurement. PMID- 27179044 TI - Echo-Guided Differential Popliteal Block in an Obese Patient With Intractable Painful Leg Ulcer for Early Discharge in Day Surgery. AB - Pain management is extremely important in day surgery, and it is one of the limiting factors for this type of procedures. Locoregional anesthesia is strongly recommended for day surgery; nevertheless, it could be very difficult to localize nerve position especially in obese patients. Furthermore, a complete nerve blockade could result in a delayed discharge. We present a case of analgesic ultrasound-guided block of tibial and common peroneal nerves in the popliteal fossa without any motor function involvement in an obese patient undergoing debridement of an infected lower limb ulcer; all previous attempts of surgical debridement in day surgery with topical anesthetics had failed because of discomfort due to pain. Our aim was to ensure an optimal degree of analgesia and, at the same time, to save motor function in order to make early discharge possible. We used 15 mL ropivacaine 0.375% to obtain a differential block, taking advantage of sensitive fibers selectivity of ropivacaine. Surgical debridement was performed successfully. Our peripheral blockade was able to provide significantly prolonged analgesia without motor block that guaranteed a safe and early discharge according to the Post Anesthetic Discharge Scoring System. The satisfaction expressed by the patient and her comfort during the procedure support the choice of this approach for intractable painful ulcers of lower limb. PMID- 27179037 TI - Macrophage PI3Kgamma Drives Pancreatic Ductal Adenocarcinoma Progression. AB - Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a low 5 year survival rate, yet new immunotherapeutic modalities may offer hope for this and other intractable cancers. Here, we report that inhibitory targeting of PI3Kgamma, a key macrophage lipid kinase, stimulates antitumor immune responses, leading to improved survival and responsiveness to standard-of-care chemotherapy in animal models of PDAC. PI3Kgamma selectively drives immunosuppressive transcriptional programming in macrophages that inhibits adaptive immune responses and promotes tumor cell invasion and desmoplasia in PDAC. Blockade of PI3Kgamma in PDAC-bearing mice reprograms tumor-associated macrophages to stimulate CD8(+) T-cell-mediated tumor suppression and to inhibit tumor cell invasion, metastasis, and desmoplasia. These data indicate the central role that macrophage PI3Kgamma plays in PDAC progression and demonstrate that pharmacologic inhibition of PI3Kgamma represents a new therapeutic modality for this devastating tumor type. SIGNIFICANCE: We report here that PI3Kgamma regulates macrophage transcriptional programming, leading to T-cell suppression, desmoplasia, and metastasis in pancreas adenocarcinoma. Genetic or pharmacologic inhibition of PI3Kgamma restores antitumor immune responses and improves responsiveness to standard-of-care chemotherapy. PI3Kgamma represents a new therapeutic immune target for pancreas cancer. Cancer Discov; 6(8); 870-85. (c)2016 AACR.This article is highlighted in the In This Issue feature, p. 803. PMID- 27179046 TI - European Board of Hand Surgery Diploma 2015 Award. PMID- 27179038 TI - High-Level Clonal FGFR Amplification and Response to FGFR Inhibition in a Translational Clinical Trial. AB - FGFR1 and FGFR2 are amplified in many tumor types, yet what determines response to FGFR inhibition in amplified cancers is unknown. In a translational clinical trial, we show that gastric cancers with high-level clonal FGFR2 amplification have a high response rate to the selective FGFR inhibitor AZD4547, whereas cancers with subclonal or low-level amplification did not respond. Using cell lines and patient-derived xenograft models, we show that high-level FGFR2 amplification initiates a distinct oncogene addiction phenotype, characterized by FGFR2-mediated transactivation of alternative receptor kinases, bringing PI3K/mTOR signaling under FGFR control. Signaling in low-level FGFR1-amplified cancers is more restricted to MAPK signaling, limiting sensitivity to FGFR inhibition. Finally, we show that circulating tumor DNA screening can identify high-level clonally amplified cancers. Our data provide a mechanistic understanding of the distinct pattern of oncogene addiction seen in highly amplified cancers and demonstrate the importance of clonality in predicting response to targeted therapy. SIGNIFICANCE: Robust single-agent response to FGFR inhibition is seen only in high-level FGFR-amplified cancers, with copy-number level dictating response to FGFR inhibition in vitro, in vivo, and in the clinic. High-level amplification of FGFR2 is relatively rare in gastric and breast cancers, and we show that screening for amplification in circulating tumor DNA may present a viable strategy to screen patients. Cancer Discov; 6(8); 838-51. (c)2016 AACR.This article is highlighted in the In This Issue feature, p. 803. PMID- 27179047 TI - Commentary on Histological assessment of the triangular fibrocartilage complex. M. Semisch, E. Hagert, M. Garcia-Elias, A. Lluch and S. Rein. J Hand Surg Eur. 2016, 41: 527-33. PMID- 27179048 TI - Re: MacFarlane RJ, Gillespie S, Cashin F, Mahmood A, Cheung G, Brown DJ. Treatment of fracture subluxations of the proximal interphalangeal joint using a ligamentotaxis device: a multidisciplinary approach. J Hand Surg Eur. 2015, 40: 825-31. PMID- 27179049 TI - Re: Cousins et al. Arm versus forearm tourniquet for carpal tunnel decompression which is better? A randomized controlled trial. J Hand Surg Eur. 2015, 40: 961 965. PMID- 27179050 TI - Ecker J, Perera N and Ebert J. Supraretinacular endoscopic carpal tunnel release: surgical technique with prospective case series. J Hand Surg Eur. 2015, 40: 193 8. PMID- 27179051 TI - Non-progressive Duypytren's disease. PMID- 27179054 TI - Comparison of the Suture Anchor and Transosseous Techniques for Patellar Tendon Repair: A Biomechanical Study. AB - BACKGROUND: Minimizing gap formation and maximizing the strength of patellar tendon repairs are 2 critical factors for successful healing of these injuries. PURPOSE/HYPOTHESIS: The purpose of this study was to compare transosseous and screw-in anchor repair techniques to determine if there is a difference in gap formation and load to failure of the 2 constructs. The research hypotheses were that the anchor construct would have significantly less gap formation and would also have significantly greater load-to-failure strength. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 24 porcine specimens were randomly assigned into transosseous and 4.75-mm polyetheretherketone (PEEK) screw in anchor repair groups. The repairs were then completed using 2 No. 2 FiberWire sutures, and each specimen was cyclically loaded on a tensile test machine to 250 N for a total of 1000 cycles. Gap formation was measured at 1, 10, 250, 500, and 1000 cycles. Each specimen was loaded to failure after 1000 cycles. Independent t tests were conducted. RESULTS: Statistically significant gap formation and load to-failure differences were found between the 2 repair techniques. The mean gap in the anchor group (2.16 +/- 1.81 mm) was significantly less than that seen in the transosseous group (5.71 +/- 1.58 mm) (P < .001). The mean load to failure of the anchor group (669.9 +/- 91.8 N) was significantly higher than that of the transosseous group (582.8 +/- 92.6 N) (P = .03). CONCLUSION: The results support the 2 study hypotheses. These findings suggest that the 4.75-mm PEEK screw-in anchor construct may be superior to the transosseous technique for minimizing gap formation and improving load-to-failure strength after surgical repair of the patellar tendon. CLINICAL RELEVANCE: The use of the suture anchor technique in patellar tendon repair may support early load-bearing rehabilitation. PMID- 27179055 TI - The ACL Graft Has Different Cross-sectional Dimensions Compared With the Native ACL: Implications for Graft Impingement. AB - BACKGROUND: Impingement of anterior cruciate ligament (ACL) grafts against the femoral notch and the posterior cruciate ligament (PCL) is thought to be influenced primarily by tunnel position and graft orientation. Recent data have implied that the native ACL is ribbon-shaped. PURPOSE: To evaluate the 3 dimensional shape and cross-sectional area of the native ACL versus the ACL graft and to compare the degree of impingement against the femoral notch and PCL. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Bilateral knee magnetic resonance images were analyzed for 27 patients with unilateral bone patellar tendon-bone (BPTB) ACL reconstruction performed via transtibial or anteromedial portal femoral tunneling techniques. Three-dimensional models of the ACL, PCL, femur, and tibia were digitally rendered. The cross-sectional area and dimensions of the native ACL and the reconstructed graft were determined at 3 equally spaced locations and compared via Wilcoxon-Mann-Whitney and Kruskal Wallis tests. In addition, impingement of the ACL on the PCL and femoral notch was graded in 3 groups. Chi-square or Fisher exact tests were used to compare the proportional differences of impingement of the native and reconstructed ACL on the PCL and femoral notch, respectively. All analyses were performed using 2 sided hypothesis testing, with statistical significance at P < .05. RESULTS: Cross-sectional areas at all 3 points on the ACL graft were significantly greater than those of the native ACL (P < .001). The long- to short-axis ratio for the native ACL was significantly greater at each location compared with the corresponding locations along the ACL graft (P < .001), implying that the native ACL is "flatter" than is an ACL graft. There were 19 operated knees (70%) with contact or impingement between the ACL graft and the femoral notch compared with zero knees with a native ACL (P < .001). In addition, 22 operated knees (81%) showed contact or impingement between the ACL graft and the PCL, compared with 7 knees (26%) with a native ACL (P < .001). No significant differences in impingement frequency were noted between the transtibial and anteromedial tunneling techniques for ACL graft specimens (P > .05). CONCLUSION: Native ACLs have a smaller cross-sectional area, are "flatter," and experience less incidence of impingement compared with anatomically placed BPTB ACL grafts. PMID- 27179056 TI - High Failure Rate of a Decellularized Osteochondral Allograft for the Treatment of Cartilage Lesions. AB - BACKGROUND: Widespread adoption of fresh allograft transplantation remains limited, predominantly by supply issues. To overcome these limitations, a preshaped, cylindrical sterilized and decellularized osteochondral allograft (SDOCA) implant was recently introduced as a clinical treatment option. PURPOSE: To evaluate functional outcomes and graft survivorship among patients treated with the SDOCA implant for knee cartilage injuries. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: An institutional review board-approved database was used to identify a series of patients with prospectively collected data who had been treated with the SDOCA implant. The surgeries were performed at 2 centers by 2 surgeons. Patient-reported outcomes, magnetic resonance imaging (MRI), and the number and type of reoperations were assessed. Failure was defined as structural damage of the graft diagnosed by arthroscopy or MRI, and any reoperation resulting in removal of the allograft. Patients were evaluated pre- and postoperatively using the Knee injury and Osteoarthritis Outcome Score (KOOS) and Marx Sports Activity Scale. MRI was assessed preoperatively and postoperatively. RESULTS: There were 32 patients with a mean age (+/-SD) of 35.1 +/- 10.6 years; 59% were male. Twenty-three (72%) knees had previous surgery. The mean defect area (+/-SD) was 2.9 +/- 2.0 cm(2), and the mean allograft size was 13.18 +/- 2.3 mm (6 grafts <=9 mm and 59 grafts >=11 mm). The median number of allografts per knee was 2 (range, 1-5 grafts). Twenty-three of the 32 knees (72%) were considered failures by the definition detailed above. Of these, 14 knees (43%) had further surgery after the index procedure. Implant survivorship was 19.6% at 2 years. The mean follow-up duration was 1.29 years (range, 0.11-2.8 years). KOOS pain, activities of daily living (ADL), sports and recreation (sport/rec), and knee-related quality of life improved significantly from the preoperative visit to latest follow-up. Age was significantly predictive of failure, with a hazard ratio of 1.68 per 1 SD older (95% CI, 1.05-2.68; P = .030). The MOCART (magnetic resonance observation of cartilage repair tissue) feature effusion was the only score to correlate with KOOS (symptoms, pain, ADL, sport/rec). CONCLUSION: The SDOCA implant demonstrated a 72% failure rate within the first 2 years of implantation at these 2 institutions. PMID- 27179058 TI - In-Hospital Management and Follow-Up Treatment of Venous Thromboembolism: Focus on New and Emerging Treatments. AB - Venous thromboembolism (VTE), encompassing pulmonary embolism (PE) and deep venous thrombosis (DVT), is a major cause of morbidity and mortality of particular relevance for intensivists and hospitalists. Acute VTE is usually managed with parenteral unfractionated heparin or low-molecular-weight heparin, followed by an oral vitamin K antagonist. Data are lacking for optimal treatment of less common occurrences, such as upper extremity DVT, and for approaches such as thrombolysis for PE associated with early signs of hemodynamic compromise or inferior vena cava filters when anticoagulation is contraindicated. Direct oral anticoagulants (DOACs) including apixaban, dabigatran, edoxaban, and rivaroxaban are now added to the armamentarium of agents available for acute management of VTE and/or reducing the risk of recurrence. This review outlines an algorithmic approach to acute VTE treatment: from aggressive therapies when anticoagulation may be inadequate, to alternative choices when anticoagulation is contraindicated, to anticoagulant options in the majority of patients in whom anticoagulation is appropriate. Evidence-based guidelines and the most recent DOAC clinical trial data are discussed in the context of the standard of care. Situations and treatment approaches for which data are unavailable or insufficient are identified. VTE therapy in care transitions is discussed, as are choices for secondary prevention. PMID- 27179057 TI - Can Creatinine Height Index Predict Weaning and Survival Outcomes in Patients on Prolonged Mechanical Ventilation After Critical Illness? AB - OBJECTIVE: Malnutrition is common in chronic critically ill patients on prolonged mechanical ventilation (PMV) and may affect weaning. The creatinine height index (CHI), which reflects lean muscle mass, is regarded as the most accurate indicator of malnutrition. The objective of this study was to determine the impact of CHI in comparison with other traditional nutritional indices on successful weaning and survival in patients on PMV after critical illness. METHODS: Records of 167 patients on PMV following critical illness, admitted for weaning, were reviewed. Parameters studied included age, gender, body mass index (BMI), percentage ideal body weight (%IBW), total protein, albumin, prealbumin, hemoglobin (Hb), and cause of respiratory failure. Number successfully weaned and number discharged alive and time to wean and time to discharge alive were determined from records. The CHI was calculated from 24-hour urine creatinine using a standard formula. Unpaired 2-sample t test was performed to determine the association between the studied nutritional parameters and outcomes. Predictive value of studied parameters for successful weaning and survival was determined by multivariate logistic regression analysis to model dichotomous outcome of successful weaning and survival. RESULTS: Mean age was 68 +/- 14 years, 49% were males, 64% were successfully weaned, and 65.8% survived. Total protein, Hb, and CHI had a significant impact on successful weaning. Weight, %IBW, BMI, and CHI had a significant effect on survival. Of all parameters, CHI was most strongly predictive of successful weaning and survival. CONCLUSIONS: The CHI is a strong predictor of successful weaning and survival in patients on PMV. PMID- 27179059 TI - Detection of Carbonaceous Aerosols Released in CNT Workplaces Using an Aethalometer. AB - OBJECTIVES: Black carbon (BC) originating from various combustion sources has been extensively surveyed to characterize the effects of BC on global warming and human health, and many online monitors are available. In this study, BC was considered as a surrogate for carbon-based nanomaterials in an occupational health study. METHODS: Specifically, BC concentrations were monitored continuously with an aethalometer for 24h at four carbon nanotube (CNT) workplaces located in rural, urban, and industrial areas, which had different background air pollution levels. Average BC concentrations for both nonworking (background) and working periods were compared with the recommended exposure limit (REL) of 1 MUg m(-3) for elemental carbon that was suggested by the National Institute for Occupational Safety and Health (NIOSH). RESULTS: Diurnal variation of BC concentrations indicated that BC measurements corresponded well with carbonaceous aerosols such as vehicle exhaust particles and CNT aerosols. In the rural CNT workplace, the average background BC concentration (0.36 MUg m(-3)) was lower than the REL, but the BC concentration without background correction was higher than the REL during manufacturing hours. In this case, BC measurement is useful to estimate CNT exposure for comparison with the REL. Conversely, in the urban and industrial CNT workplaces, average background BC concentrations (2.05, 1.82, and 2.64 MUg m(-3)) were well above the REL, and during working hours, BC concentrations were substantially higher than the background level at workplace C; however, BC concentrations showed no difference from the background levels at workplaces B and D. In these cases (B and D), it is hard to determine CNT exposure because of the substantial environmental exposures. CONCLUSION: Most of the urban ambient BC concentrations were above the REL. Therefore, further analysis and test methods for carbonaceous aerosols need to be developed so that the exposure assessment can be easily carried out at CNT workplaces with high background BC levels such as in urban and industrial areas. PMID- 27179060 TI - The Impact of Vocational Education and Training Programs on Recidivism: A Systematic Review of Current Experimental Evidence. AB - Although the association between unemployment and offending is well established, relatively little is known about the impact of vocational education and training programs on re-offending, with much of the previous work in this area failing to control for, or correct, selection bias. This article reports the findings of a systematic review, which considers the findings of only those studies that have used experimental or quasi-experimental designs to evaluate vocational training and employment program outcomes for adult offenders. The analysis identifies key features, based on these studies, of those programs associated with the best outcomes and recommends selection criteria for those who are most likely to benefit from prison vocational education and training. PMID- 27179061 TI - Violent Female Offenders Compared With Violent Male Offenders on Psychological Determinants of Aggressive Behavior. AB - Psychological determinants of aggressive behavior (personality traits and problem behaviors) in 59 Dutch female offenders (outpatients and detainees) were compared with those in 170 male offenders (outpatients and detainees) who were all convicted of a violent crime. The violent female offenders scored significantly higher on neuroticism and trait anger, and significantly lower on hostility than the male offenders; however, effect sizes were small. A subgroup of female forensic psychiatric outpatients did not differ from a subgroup of male outpatients on all measures, whereas a subgroup of female detainees scored significantly higher on anger and aggression, but lower on hostility and psychopathy than did a subgroup of male detainees. These first results might indicate that violent female offenders do not differ much from violent male offenders regarding personality traits and problem behaviors. The differences between both groups of violent offenders were largely borne by the subgroup of violent female detainees compared with the subgroup of violent male detainees. PMID- 27179062 TI - Narratives of Compensated Dating of Girls in Hong Kong Using Routine Activity Theory: Results of a Focus Group Study of Guardians. AB - This article presents public discourses on compensated dating of adolescent girls in Chinese society. Data are obtained from eight focus groups comprising 50 guardians at private, parochial, and public levels (i.e., social workers, police officers, parents of students, and community representatives). Qualitative data are used to demonstrate how the guardians conceptualize and contextualize compensated dating as an outcome of the dynamics of societal features. Social features such as contemporary ideologies, Internet technology advancement, commercialization of human relationships, and ambiguity between "right" and "wrong" motivate the service providers and customers of compensated dating, and accelerate their convergence and weakened levels of guardianship in society. This study is the first to connect the features of compensated dating of adolescent girls with recent societal changes using the routine activity approach. The findings confirm the application of the routine activity approach in the phenomenon of girls' compensated dating, and also offer theoretical and practical implications. PMID- 27179063 TI - Roles of Social Movement Organizations for Securing Workers' Safety in Korea: A Case Study of Abolition of the 30-Minute Delivery Guarantee Program in Pizza Delivery Service. AB - Many restaurants in Korea maintain quick-delivery service programs to satisfy customers. This service allows delivery workers limited time to deliver, which frequently put them in danger. Most of the workers are young, work part-time, and are rarely organized into trade unions. In this article, through a case study of the social movement to abolish the 30-minute delivery guarantee program of pizza companies in Korea, we argue that social movements involving social movement organizations (SMOs) and individual citizens could serve as a means to rectify this problem. We show how the SMOs developed and expanded the movement using a framing perspective and how the general public became involved through social media. Data was collected via online searching. Interview scripts from key players of SMOs and unofficial documents they provided were also reviewed. Three SMOs primarily led the movement, successfully forming a frame that emphasized social responsibility. SMOs also utilized social media to link their standing frame with unmobilized citizens and to expand the movement. We identified contributing factors and limitations of the movement and drew lessons that could be applied to other sectors where workers are in vulnerable positions. PMID- 27179064 TI - Classic Spotlight: Cyclic Di-GMP, the Molecule That Makes the Bacterial World Stop Going 'Round. PMID- 27179069 TI - ABN news. PMID- 27179065 TI - Classic Spotlight: Visualization of Bacterial Genes in Action. PMID- 27179070 TI - Human traces. PMID- 27179071 TI - The membrane attack complex, perforin and cholesterol-dependent cytolysin superfamily of pore-forming proteins. AB - The membrane attack complex and perforin proteins (MACPFs) and bacterial cholesterol-dependent cytolysins (CDCs) are two branches of a large and diverse superfamily of pore-forming proteins that function in immunity and pathogenesis. During pore formation, soluble monomers assemble into large transmembrane pores through conformational transitions that involve extrusion and refolding of two alpha-helical regions into transmembrane beta-hairpins. These transitions entail a dramatic refolding of the protein structure, and the resulting assemblies create large holes in cellular membranes, but they do not use any external source of energy. Structures of the membrane-bound assemblies are required to mechanistically understand and modulate these processes. In this Commentary, we discuss recent advances in the understanding of assembly mechanisms and molecular details of the conformational changes that occur during MACPF and CDC pore formation. PMID- 27179072 TI - Aggregation dynamics and identification of aggregation-prone mutants of the von Hippel-Lindau tumor suppressor protein. AB - Quality control mechanisms promote aggregation and degradation of misfolded proteins. In budding yeast, the human von Hippel-Lindau protein (pVHL, officially known as VHL) is misfolded and forms aggregates. Here, we investigated the aggregation of three pVHL isoforms (pVHL213, pVHL160, pVHL172) in fission yeast. The full-length pVHL213 isoform aggregates in highly dynamic small puncta and in large spherical inclusions, either close to the nucleus or to the cell ends. The large inclusions contain the yeast Hsp104 chaperone. Aggregate clearance is regulated by proteasomal degradation. The pVHL160 isoform forms dense foci and large irregularly shaped aggregates. In silico, prediction of pVHL aggregation propensity identified a key aggregation-promoting region within exon 2. Consistently, the pVHL172 isoform, which lacks exon 2, formed rare reduced inclusions. We studied the aggregation propensity of pVHL variants harbouring missense mutations found in kidney carcinomas. We show that the P86L mutation stimulated small aggregate formation, the P146A mutation increased large inclusion formation, whereas the I151S mutant destabilized pVHL. The prefoldin subunit Pac10 (the human homolog VBP-1 binds to pVHL) is required for pVHL stability. Reduction of soluble functional pVHL might be crucial in VHL-related diseases. PMID- 27179073 TI - From meiosis to mitosis - the sperm centrosome defines the kinetics of spindle assembly after fertilization in Xenopus. AB - Bipolar spindle assembly in the vertebrate oocyte relies on a self-organization chromosome-dependent pathway. Upon fertilization, the male gamete provides a centrosome, and the first and subsequent embryonic divisions occur in the presence of duplicated centrosomes that act as dominant microtubule organizing centres (MTOCs). The transition from meiosis to embryonic mitosis involves a necessary adaptation to integrate the dominant chromosome-dependent pathway with the centrosomes to form the bipolar spindle. Here, we took advantage of the Xenopus laevis egg extract system to mimic in vitro the assembly of the first embryonic spindle and investigate the respective contributions of the centrosome and the chromosome-dependent pathway to the kinetics of the spindle bipolarization. We found that centrosomes control the transition from the meiotic to the mitotic spindle assembly mechanism. By defining the kinetics of spindle bipolarization, the centrosomes ensure their own positioning to each spindle pole and thereby their essential correct inheritance to the two first daughter cells of the embryo for the development of a healthy organism. PMID- 27179075 TI - Cortactin is a scaffolding platform for the E-cadherin adhesion complex and is regulated by protein kinase D1 phosphorylation. AB - Dynamic regulation of cell-cell adhesion by the coordinated formation and dissolution of E-cadherin-based adherens junctions is crucial for tissue homeostasis. The actin-binding protein cortactin interacts with E-cadherin and enables F-actin accumulation at adherens junctions. Here, we were interested to study the broader functional interactions of cortactin in adhesion complexes. In line with literature, we demonstrate that cortactin binds to E-cadherin, and that a posttranslational modification of cortactin, RhoA-induced phosphorylation by protein kinase D1 (PKD1; also known as PRKD1) at S298, impairs adherens junction assembly and supports their dissolution. Two new S298-phosphorylation-dependent interactions were also identified, namely, that phosphorylation of cortactin decreases its interaction with beta-catenin and the actin-binding protein vinculin. In addition, binding of vinculin to beta-catenin, as well as linkage of vinculin to F-actin, are also significantly compromised upon phosphorylation of cortactin. Accordingly, we found that regulation of cell-cell adhesion by phosphorylation of cortactin downstream of RhoA and PKD1 is vitally dependent on vinculin-mediated protein interactions. Thus, cortactin, unexpectedly, is an important integration node for the dynamic regulation of protein complexes during breakdown and formation of adherens junctions. PMID- 27179077 TI - Pedigree Dogs Exposed director issues a challenge to UK vets. PMID- 27179087 TI - Equine disease surveillance: quarterly summary. AB - Multiple reports of equine herpesvirus type 1 in the UKFirst cases of dourine in Botswana and equine infectious anaemia in GreeceSummary of UK surveillance testing, October to December 2015These are among matters discussed in the most recent quarterly equine disease surveillance report, prepared by Defra, the Animal Health Trust and the British Equine Veterinary Association. PMID- 27179074 TI - Scribble is required for pregnancy-induced alveologenesis in the adult mammary gland. AB - The cell polarity protein scribble (SCRIB) is a crucial regulator of polarization, cell migration and tumorigenesis. Whereas SCRIB is known to regulate early stages of mouse mammary gland development, its function in the adult gland is not known. Using an inducible RNA interference (RNAi) mouse model for downregulating SCRIB expression, we report an unexpected role for SCRIB as a positive regulator of cell proliferation during pregnancy-associated mammary alveologenesis. SCRIB was required in the epithelial cell compartment of the mammary gland. Lack of SCRIB attenuated prolactin-induced activation of the JAK2 STAT5 signaling pathway. In addition, loss of SCRIB resulted in the downregulation of prolactin receptor (PRLR) at cell surface and its accumulation in intracellular structures that express markers of the Golgi complex and the recycling endosome. Unlike its role in virgin gland as a negative regulator cell proliferation, SCRIB is a positive regulator of mammary epithelial cell proliferation during pregnancy. PMID- 27179088 TI - Equine herpesvirus - a constant threat. AB - Camilla Strang of the Animal Health Trust provides an overview of the diagnosis and control of conditions associated with infection by equine herpesvirus. PMID- 27179089 TI - Target-controlled infusion in small animals: improving anaesthetic safety. PMID- 27179090 TI - Allergic wheals, abortion and lumpy skin disease. PMID- 27179091 TI - EU membership and animal health and welfare. PMID- 27179092 TI - Left displaced abomasum: pilot survey of corrective techniques. PMID- 27179093 TI - Experience of reflective practice. PMID- 27179095 TI - RCVS Council elections. PMID- 27179094 TI - Reporting cases of Fanconi syndrome in dogs in the UK. PMID- 27179101 TI - Advancing as a surgeon. AB - A year ago, Padraig Egan enrolled on the European College of Veterinary Surgeons' residency programme, but he admits that it's only now that he realises how much work is involved. PMID- 27179102 TI - Second-year student diary. AB - Rosie Perrett is happy! This term has involved completing major pieces of course work. However, as she loves numbers, she enjoyed completing an enterprise report that involved calculating energy requirements in horses. She also completed her third literature review and learned that typos can be embarrassing and amusing, but are best avoided. PMID- 27179103 TI - A preliminary study showing that ultrasonography cannot differentiate between psoriatic arthritis and nodal osteoarthritis based on enthesopathy scores. PMID- 27179105 TI - Thoracic aortic aneurysms in Behcet's disease. PMID- 27179104 TI - Reduced CLEC9A expression in synovial tissue of psoriatic arthritis patients after adalimumab therapy. AB - OBJECTIVES: We aimed to investigate the early changes in expression of C-type lectin domain family 9, member A (CLEC9A), a C-type lectin that is specifically expressed by the CD141(+) dendritic cell subset that is involved in cross presentation to CD8(+) T cells, by evaluating gene and/or protein expression in three different compartments [skin, synovial tissue (ST) and serum] after short term adalimumab treatment in PsA patients compared with placebo. METHODS: Patients with active PsA and psoriasis were randomized to receive adalimumab or placebo for 4 weeks. Synovial and skin biopsies were obtained before and after 4 weeks of treatment and serum samples 4 weeks, 12 weeks and 1 year after treatment. Skin and serum from healthy donors were used as control. CLEC9A expression was assessed by immunohistochemistry, double immunofluorescence using terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'-triphosphate nick-end labelling (TUNEL), quantitative PCR and ELISA. RESULTS: CLEC9A expression was significantly higher in psoriatic skin compared with healthy donor. In psoriatic skin and PsA ST, CLEC9A(+) cells were in close proximity to TUNEL(+) cells. SF CLEC9A levels were significantly lower compared with paired PsA serum. Adalimumab treatment did not affect CLEC9A serum level and skin expression. However, ST CLEC9A protein expression was significantly decreased after adalimumab treatment compared with the placebo group while CLEC9A gene expression remained unchanged. There was a positive correlation between T cell numbers and ST CLEC9A protein expression. CD141(+) cell numbers and chemokine (C motif) receptor 1 expression were not affected with adalimumab treatment. CONCLUSION: Altogether, the present study suggests that the downregulation of synovial CLEC9A might be associated with a novel mechanism by which anti-TNF therapy might reduce CD8-mediated inflammation in PsA patients. PMID- 27179107 TI - Effectiveness of add-on therapy with domperidone vs alginic acid in proton pump inhibitor partial response gastro-oesophageal reflux disease in systemic sclerosis: randomized placebo-controlled trial. AB - OBJECTIVES: Twice-daily dosing of proton pump inhibitor (PPI), the standard therapy for gastro-oesophageal reflux disease (GERD), is an effective therapy for GERD in SSc. The aim of this study was to compare the efficacy of omeprazole in combination with domperidone vs in combination with algycon in reducing the severity and frequency of reflux symptoms of PPI partial response (PPI-PR) GERD in SSc. METHODS: Adult SSc patients having PPI-PR GERD were randomly assigned to receive domperidone plus algycon placebo or algycon plus domperidone placebo in a 1:1 ratio plus omeprazole for 4 weeks. The assessment included severity of symptom grading by visual analogue scale, frequency of symptoms by frequency scale for symptoms of GERD and quality of life (QoL) by EuroQol five-dimensions questionnaire scoring. RESULTS: One hundred and forty-eight SSc-GERD patients were enrolled, of whom 88 had PPI-PR. Eighty cases were randomized for either domperidone (n = 38) or algycon (n = 37) therapy. The majority in both groups had the diffuse SSc subset. At the end of the study, no significant difference in symptom grading was found between groups. After treatment and compared with baseline, the severity of symptoms, frequency scale for symptoms of GERD and QoL significantly improved in both groups. Five (13.2%) and 8 (21.6%) respective cases in the domperidone and algycon groups did not respond. CONCLUSION: The prevalence of PPI-PR GERD is common. Domperidone and algycon are equally effective treatments in combination with omeprazole. However, ~17% of patients were non-responsive, so the effectiveness of domperidone, algycon and PPI combination therapy should be further investigated. TRIAL REGISTRATION: https://clinicaltrials.gov (NCT01878526). PMID- 27179106 TI - Vitamin D treatment for connective tissue diseases: hope beyond the hype? AB - The prevalence of vitamin D deficiency is increased among patients with CTDs. The active form of vitamin D (calcitriol) is a potent regulator of the immune system and may suppress inflammatory responses. This has led to claims that vitamin D may be a safe treatment, or a treatment adjunct, to reduce systemic inflammation in this patient population. It is important to note, however, that there is insufficient evidence from robust clinical trials to support these novel uses for vitamin D. In this review we examine the potential role of vitamin D as a treatment adjunct for CTDs. We will discuss how vitamin D may modulate the immune response and review the current evidence for using vitamin D to treat CTDs and their associated co-morbidities. We conclude that while there is much excitement about vitamin D in this context, further well-designed trials are needed to demonstrate its efficacy in the treatment of patients with CTDs. PMID- 27179109 TI - Precise expression of Fis1 is important for glucose responsiveness of beta cells. AB - Mitochondrial network functionality is vital for glucose-stimulated insulin secretion in pancreatic beta cells. Altered mitochondrial dynamics in pancreatic beta cells are thought to trigger the development of type 2 diabetes mellitus. Fission protein 1 (Fis1) might be a key player in this process. Thus, the aim of this study was to investigate mitochondrial morphology in dependence of beta cell function, after knockdown and overexpression of Fis1. We demonstrate that glucose unresponsive cells with impaired glucose-stimulated insulin secretion (INS1 832/2) showed decreased mitochondrial dynamics compared with glucose-responsive cells (INS1-832/13). Accordingly, mitochondrial morphology visualised using MitoTracker staining differed between the two cell lines. INS1-832/2 cells formed elongated and clustered mitochondria, whereas INS1-832/13 cells showed a homogenous mitochondrial network. Fis1 overexpression using lentiviral transduction significantly improved glucose-stimulated insulin secretion and mitochondrial network homogeneity in glucose-unresponsive cells. Conversely, Fis1 downregulation by shRNA, both in primary mouse beta cells and glucose-responsive INS1-832/13 cells, caused unresponsiveness and significantly greater numbers of elongated mitochondria. Overexpression of FIS1 in primary mouse beta cells indicated an upper limit at which higher FIS1 expression reduced glucose stimulated insulin secretion. Thus, FIS1 was overexpressed stepwise up to a high concentration in RINm5F cells using the RheoSwitch system. Moderate FIS1 expression improved glucose-stimulated insulin secretion, whereas high expression resulted in loss of glucose responsiveness and in mitochondrial artificial loop structures and clustering. Our data confirm that FIS1 is a key regulator in pancreatic beta cells, because both glucose-stimulated insulin secretion and mitochondrial dynamics were clearly adapted to precise expression levels of this fission protein. PMID- 27179108 TI - Prenatal hyperandrogenism induces alterations that affect liver lipid metabolism. AB - Prenatal hyperandrogenism is hypothesized as one of the main factors contributing to the development of polycystic ovary syndrome (PCOS). PCOS patients have high risk of developing fatty liver and steatosis. This study aimed to evaluate the role of prenatal hyperandrogenism in liver lipid metabolism and fatty liver development. Pregnant rats were hyperandrogenized with testosterone. At pubertal age, the prenatally hyperandrogenized (PH) female offspring displayed both ovulatory (PHov) and anovulatory (PHanov) phenotypes that mimic human PCOS features. We evaluated hepatic transferases, liver lipid content, the balance between lipogenesis and fatty acid oxidation pathway, oxidant/antioxidant balance and proinflammatory status. We also evaluated the general metabolic status through growth rate curve, basal glucose and insulin levels, glucose tolerance test, HOMA-IR index and serum lipid profile. Although neither PH group showed signs of liver lipid content, the lipogenesis and fatty oxidation pathways were altered. The PH groups also showed impaired oxidant/antioxidant balance, a decrease in the proinflammatory pathway (measured by prostaglandin E2 and cyclooxygenase-2 levels), decreased glucose tolerance, imbalance of circulating lipids and increased risk of metabolic syndrome. We conclude that prenatal hyperandrogenism generates both PHov and PHanov phenotypes with signs of liver alterations, imbalance in lipid metabolism and increased risk of developing metabolic syndrome. The anovulatory phenotype showed more alterations in liver lipogenesis and a more impaired balance of insulin and glucose metabolism, being more susceptible to the development of steatosis. PMID- 27179111 TI - Changes in Expression of Genes Representing Key Biologic Processes after Neoadjuvant Chemotherapy in Breast Cancer, and Prognostic Implications in Residual Disease. AB - PURPOSE: The primary aim was to derive evidence for or against the clinical importance of several biologic processes in patients treated with neoadjuvant chemotherapy (NAC) by assessing expression of selected genes with prior implications in prognosis or treatment resistance. The secondary aim was to determine the prognostic impact in residual disease of the genes' expression. EXPERIMENTAL DESIGN: Expression levels of 24 genes were quantified by NanoString nCounter on formalin-fixed paraffin-embedded residual tumors from 126 patients treated with NAC and 56 paired presurgical biopsies. The paired t test was used for testing changes in gene expression, and Cox regression and penalized elastic net Cox Regression for estimating HRs. RESULTS: After NAC, 12 genes were significantly up- and 8 downregulated. Fourteen genes were significantly associated with time to recurrence in univariable analysis in residual disease. In a multivariable model, ACACB, CD3D, MKI67, and TOP2A added prognostic value independent of clinical ER(-), PgR(-), and HER2(-) status. In ER(+)/HER2(-) patients, ACACB, PAWR, and ERBB2 predicted outcome, whereas CD3D and PAWR were prognostic in ER(-)/HER2(-) patients. By use of elastic-net analysis, a 6-gene signature (ACACB, CD3D, DECORIN, ESR1, MKI67, PLAU) was identified adding prognostic value independent of ER, PgR, and HER2. CONCLUSIONS: Most of the tested genes were significantly enriched or depleted in response to NAC. Expression levels of genes representing proliferation, stromal activation, metabolism, apoptosis, stemcellness, immunologic response, and Ras-ERK activation predicted outcome in residual disease. The multivariable gene models identified could, if validated, be used to identify patients needing additional post neoadjuvant treatment to improve prognosis. Clin Cancer Res; 22(10); 2405-16. (c)2016 AACR. PMID- 27179113 TI - The MEK1/2 Inhibitor Pimasertib Enhances Gemcitabine Efficacy-Letter. PMID- 27179112 TI - Fc-gamma Receptor Polymorphisms, Cetuximab Therapy, and Survival in the NCIC CTG CO.17 Trial of Colorectal Cancer. AB - PURPOSE: Two germline Fc-gamma receptor (FCGR) polymorphisms, rs1801274 [FCGR2A;His(H)131Arg(R)] and rs396991 [FCGR3A;Phe(F)158Val(V)] produce altered proteins through amino acid substitutions; both are reported to be associated with cetuximab-related outcomes. We performed a validation of these polymorphisms in NCIC CTG CO.17, a randomized trial of cetuximab monotherapy in refractory, metastatic colorectal cancer expressing EGFR. EXPERIMENTAL DESIGN: DNA extracted from formalin-fixed paraffin-embedded tissue was genotyped. In addition to log rank tests, Cox proportional hazard models assessed their relationships with overall (OS) and progression-free survival (PFS), adjusting for clinically important prognostic factors, along with a polymorphism-treatment arm interaction term. RESULTS: Somatic KRAS status was wild-type for exon 2 in 153 (52%) of 293 patients, from whom tumor DNA was available. For FCGR2A H/H, a genotype-treatment interaction for KRAS wild-type patients was observed for OS (P = 0.03). In KRAS wild-type patients carrying FCGR2A H/H, cetuximab (vs. no cetuximab) improved survival substantially, with adjusted HRs (aHR) of 0.36 (OS) and 0.19 (PFS) and absolute benefits of 5.5 months (OS; P = 0.003) and 3.7 months (PFS; P = 0.02). In contrast, patients carrying FCGR2A R alleles (H/R or R/R) had aHRs of only 0.78 (OS; 2.8-month benefit) and 0.53 (PFS; 1.6-month benefit). No relationships were found for rs396991 (FCGR3A). CONCLUSIONS: In the CO.17 trial, cetuximab worked best for patients with KRAS wild-type colorectal cancers carrying FCGR2A H/H genotypes. Significantly lower benefits were observed in patients carrying germline FCGR2A R alleles. Clin Cancer Res; 22(10); 2435-44. (c)2016 AACR. PMID- 27179114 TI - The MEK1/2 Inhibitor Pimasertib Enhances Gemcitabine Efficacy-Response. PMID- 27179115 TI - Correction: A First-in-Human Phase I Study of the Oral p38 MAPK Inhibitor, Ralimetinib (LY2228820 Dimesylate), in Patients with Advanced Cancer. PMID- 27179116 TI - Di-Calcium Phosphate and Phytosphingosine as an Innovative Acid-Resistant Treatment to Occlude Dentine Tubules. AB - The present investigation evaluated the ability of an experimental di-calcium phosphate (DCP) desensitising agent used alone or combined with phytosphingosine (PHS) to occlude dentine tubules and resist a citric acid (CA) or artificial saliva (AS) challenge. Three groups of human dentine specimens (DS) were treated with the following: (1) PHS alone, (2) DCP or (3) a combination of PHS and DCP. Dentine hydraulic conductance of DS was evaluated using a digital flow sensor at 6.9 kPa. The average fluid volume for each of the treated DS was used to calculate the total dentine permeability reduction (%P) prior to and following CA immersion for 1 min or AS immersion for 4 weeks. The treated DS were subjected to both scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) spectroscopy analysis. Statistically significant differences (%P) were identified between the groups by ANOVA and Fisher's multiple comparison test (p < 0.05), respectively. Interestingly, both PHS and DCP appeared to work synergistically. DS treated with DCP or PHS/DCP demonstrated a significant reduction (%P) prior to and following CA or AS challenge (p < 0.05). Both the SEM and FTIR analyses showed consistent brushite crystals occluding the dentine tubules. Conversely, the application of PHS alone failed to demonstrate any significant reduction of dentine permeability (p > 0.05) or show any evidence of occlusion of the dentine tubules. DCP can be used alone or combined with PHS to decrease the dentine permeability as well as to resist a CA and AS challenge. These results would, therefore, suggest that DCP may be a suitable treatment option for dentine hypersensitivity. PMID- 27179117 TI - Instruction and Service Time Decisions: Itinerant Services to Deaf and Hard-of Hearing Students. AB - The purpose of this study was to (a) describe the specific kinds of services provided by itinerant teachers to deaf and hard-of-hearing (DHH) students in general education settings, (b) examine the relationship between student academic performance and instructional support provided by the itinerant teacher, and (c) examine how service provision decisions are made by itinerant teachers. We used quantitative and qualitative data collected during a 5-year longitudinal study. Data were obtained from teacher questionnaires, standardized achievement tests, and interviews. Results indicated that itinerant teachers of DHH students provided direct academic instruction to 60% of students with the majority of students receiving instruction in reading and writing. They provided instruction in nonacademic areas to 80% of students with a majority of students receiving instruction in self-advocacy. Low-achieving students were the most likely to receive academic instruction from the itinerant teacher. Decisions regarding service time were influenced by student needs and performance, age, parental request, and transitions. PMID- 27179118 TI - Family-Based Genetic Association for Molar-Incisor Hypomineralization. AB - Despite some evidence of genetic and environmental factors on molar-incisor hypomineralization (MIH), its aetiology remains unclear. This family-based genetic association study aimed more comprehensively to investigate the genetic carriage potentially involved in MIH development. DNA was obtained from buccal cells of 391 individuals who were birth family members of 101 Brazilian nuclear families. Sixty-three single nucleotide polymorphisms (SNPs) were investigated in 21 candidate genes related to amelogenesis using the TaqManTM OpenArrayTM Genotyping platform. All SNPs were genotyped in 165 birth family members unaffected by MIH, 96 with unknown MIH status and 130 affected individuals (50.7% with severe MIH). Association analysis was performed by the transmission/disequilibrium test (TDT), and statistical results were corrected using the false discovery rate. Significant results were obtained for SNPs rs7821494 (FAM83H gene, OR = 3.7; 95% CI = 1.75-7.78), rs34367704 (AMBN gene, OR = 2.7; 95% CI = 1.16-6.58), rs3789334 (BMP2 gene, OR = 2.9; 95% CI = 1.34-6.35), rs6099486 (BMP7 gene, OR = 2.2; 95% CI = 1.14-4.38), rs762642 (BMP4 gene, OR = 2.3; 95% CI = 1.38-3.65), rs7664896 (ENAM gene, OR = 2.1; 95% CI = 1.19-3.51), rs1711399 (MMP20 gene, OR = 0.4; 95% CI = 0.20-0.72), rs1711423 (MMP20 gene, OR = 2.1; 95% CI = 1.18-3.61), rs2278163 (DLX3 gene, OR = 2.8; 95% CI = 1.26-6.41), rs6996321 (FGFR1 gene, OR = 2.7; 95% CI = 1.20-5.88), and rs5979395 (AMELX gene, OR = 11.7; 95% CI = 1.63-84.74). Through this family-based association study, we concluded that variations in genes related to amelogenesis were associated with the susceptibility to develop MIH. This result is in agreement with the multifactorial idea of the MIH aetiology, but further studies are necessary to investigate more thoroughly the factors that could influence MIH. PMID- 27179119 TI - 14C BOMB-PULSE DATING AND STABLE ISOTOPE ANALYSIS FOR GROWTH RATE AND DIETARY INFORMATION IN BREAST CANCER? AB - The purpose of this study was to perform an initial investigation of the possibility to determine breast cancer growth rate with (14)C bomb-pulse dating. Tissues from 11 breast cancers, diagnosed in 1983, were retrieved from a regional biobank. The estimated average age of the majority of the samples overlapped the year of collection (1983) within 3sigma Thus, this first study of tumour tissue has not yet demonstrated that (14)C bomb-pulse dating can obtain information on the growth of breast cancer. However, with further refinement, involving extraction of cell types and components, there is a possibility that fundamental knowledge of tumour biology might still be gained by the bomb-pulse technique. Additionally, delta (13)C and delta (15)N analyses were performed to obtain dietary and metabolic information, and to serve as a base for improvement of the age determination. PMID- 27179120 TI - COMPARISON METHODOLOGIES FOR CALIBRATION OF Hp(10) PERSONAL DOSEMETERS USING ISO 4037 AND ISO 29661 STANDARDS. AB - The calibration of electronic personal dosemeters at the Portuguese ionizing radiation metrology laboratory uses the standard IEC 61526 for calibration methodology. This standard describes the irradiation geometry for testing and indicates that the standard ISO 4037-1, 2, 3 and 4 should be used. The ISO 4037 establishes that the reference point of test is a point in the radiation monitor, known or established, and the calibration phantom should be placed on its back in order to simulate the trunk body. Recently, ISO published another standard, the ISO 29661, that changes the reference point from the radiation monitor to the front face of the calibration phantom. The aim of this work is to present the result of the comparison of these two methodologies on personal dosemeters from five different manufacturers. The work shows differences in the Hp(10) response up to 4% resulting from the two different reference point concepts. PMID- 27179121 TI - EXPERIENCES IN DEVELOPING A NATIONAL DOSE REGISTER IN FINLAND AND MERGING IT WITH THE OVERALL SUPERVISORY DATA SYSTEM. AB - In recent years, a new national Dose Register has been under development in Finland. This article presents this work, the challenges in the project, the features of the new register and experiences in using it. There were several motivations for creating a new register. The technical implementation of the existing Dose Register needed to be reformed, and there was also a need to improve electronic communication and access to the recorded data. The development was challenging and took more time and effort than expected. Despite the challenges, the new system works quite reliably and enables the use of the registered data to more easily improve radiation safety. PMID- 27179122 TI - DOSE TO RADIOLOGICAL TECHNOLOGISTS FROM INDUCED RADIONUCLIDES IN CARBON ION RADIOTHERAPY. AB - Radioactive nuclides are induced in irradiation devices and patients during high energy photon and ion beam radiotherapies. These nuclides potentially become sources of exposure to radiation workers. Radiological technologists (RTs) are often required to enter an irradiation room and approach activated devices and patients. In this study, annual doses to RTs working in a carbon ion radiotherapy facility were estimated based on measurements with the Si-semiconductor personal dosemeter. In addition, the time decay of dose around a patient couch after irradiation was obtained by phantom experiments. The annual Hp(10) values for passive and scanned beams were estimated to be 61 and 2 MUSv, respectively, when assuming the number of treatments in 2013. These are much lower than the ICRP recommended dose limit for radiation workers. The time-series data of dose to RTs during their work and the time decay of the dose should be helpful for reducing their dose further. PMID- 27179123 TI - Evidence Supporting a Paracrine Effect of IGF-1/VEGF on Human Mesenchymal Stromal Cell Commitment. AB - Healing of skeletal defects is strictly dependent on osteogenesis and efficient vascularization of engineered scaffolds. Insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) are both involved in these processes. The in vitro administration of IGF-1 in association with VEGF is able to modulate the osteoblastic or endothelial commitment of mesenchymal stromal cells (MSCs) of different origins (e.g. periosteum and skin). In the present study, in order to deepen a possible paracrine effect of IGF-1 and VEGF on periosteum-derived progenitor cells (PDPCs) and skin-derived MSCs (S-MSCs), a Transwell coculture approach was used. We explored the genes involved in endothelial and osteoblastic differentiation, those modulating mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3'-kinase (PI3K)-AKT signaling pathways as well as genes implicated in stemness (i.e. Sox2, Oct4, and Nanog). Periosteal cells, which are typically committed toward osteoblastogenesis, are driven in the direction of endothelial gene expression when influenced by S-MSCs. The latter, once influenced by PDPCs, lose their endothelial commitment and increase the expression of osteoblast-associated genes. PI3K/AKT and MAPK signaling pathways seem to be markedly involved in this behavior. Our results evidence that paracrine signals between MSCs may differently modulate their commitment in a bone microenvironment, opening stimulating viewpoints for skeletal tissue engineering strategies coupling angiogenesis and osteogenesis processes. PMID- 27179124 TI - A Network Approach to Environmental Impact in Psychotic Disorder: Brief Theoretical Framework. AB - The spectrum of psychotic disorder represents a multifactorial and heterogeneous condition and is thought to result from a complex interplay between genetic and environmental factors. In the current paper, we analyze this interplay using network analysis, which has been recently proposed as a novel psychometric framework for the study of mental disorders. Using general population data, we construct network models for the relation between 3 environmental risk factors (cannabis use, developmental trauma, and urban environment), dimensional measures of psychopathology (anxiety, depression, interpersonal sensitivity, obsessive compulsive disorder, phobic anxiety, somatizations, and hostility), and a composite measure of psychosis expression. Results indicate the existence of specific paths between environmental factors and symptoms. These paths most often involve cannabis use. In addition, the analyses suggest that symptom networks are more strongly connected for people exposed to environmental risk factors, implying that environmental exposure may lead to less resilient symptom networks. PMID- 27179125 TI - Mild Reinforcement Learning Deficits in Patients With First-Episode Psychosis. AB - Numerous studies have identified reinforcement learning (RL) deficits in schizophrenia. Most have focused on chronic patients with longstanding antipsychotic treatment, however, and studies of RL in early-illness patients have produced mixed results, particularly regarding gradual/procedural learning. No study has directly contrasted both rapid and gradual RL in first-episode psychosis (FEP) samples. We examined probabilistic RL in 34 FEP patients and 36 controls, using Go/NoGo (GNG) and Gain vs Loss-Avoidance (GLA) paradigms. Our results were mixed, with FEP patients exhibiting greater impairment in the ability to use positive, as opposed to negative, feedback to drive rapid RL on the GLA, but not the GNG. By contrast, patients and controls showed similar improvement across the acquisition. Finally, we found no significant between group differences in the postacquisition expression of value-based preference in both tasks. Negative symptoms were modestly associated with RL measures, while the overall bias to engage in Go-responding correlated significantly with psychosis severity in FEP patients, consistent with striatal hyperdopaminergia. Taken together, FEP patients demonstrated more circumscribed RL impairments than previous studies have documented in chronic samples, possibly reflecting differential symptom profiles between first-episode and chronic samples. Our finding of relatively preserved gradual/procedural RL, in briefly medicated FEP patients, might suggest spared or restored basal ganglia function. Our findings of preserved abilities to use representations of expected value to guide decision making, and our mixed results regarding rapid RL, may reflect a lesser degree of prefrontal cortical functional impairment in FEP than in chronic samples. Further longitudinal research, in larger samples, is required. PMID- 27179126 TI - Metabolism and Disposition of Hepatitis C Polymerase Inhibitor Dasabuvir in Humans. AB - Dasabuvir [also known as ABT-333 or N-(6-(3-(tert-butyl)-5-(2,4-dioxo-3,4 dihydropyrimidin-1(2H)-yl)-2-methoxyphenyl)naphthalen-2-yl)methanesulfonamide] is a potent non-nucleoside NS protein 5B polymerase inhibitor of the hepatitis C virus (HCV) and is being developed in combination with paritaprevir/ritonavir and ombitasvir in an oral regimen with three direct-acting antivirals for the treatment of patients infected with HCV genotype 1. This article describes the mass balance, metabolism, and disposition of dasabuvir in humans. After administration of a single oral dose of 400-mg [(14)C]dasabuvir (without coadministration of paritaprevir/ritonavir and ombitasvir) to four healthy male volunteers, the mean total percentage of the administered radioactive dose recovered was 96.6%. The recovery from the individual subjects ranged from 90.8% to 103%. Dasabuvir and corresponding metabolites were predominantly eliminated in feces (94.4% of the dose) and minimally through renal excretion (2.2% of the dose). The biotransformation of dasabuvir primarily involves hydroxylation of the tert-butyl group to form active metabolite M1 [N-(6-(5-(2,4-dioxo-3,4 dihydropyrimidin-1(2H)-yl)-3-(1-hydroxy-2-methylpropan-2-yl)-2 methoxyphenyl)naphthalen-2-yl)methanesulfonamide], followed by glucuronidation and sulfation of M1 and subsequent secondary oxidation. Dasabuvir was the major circulating component (58% of total radioactivity) in plasma, followed by metabolite M1 (21%). Other minor metabolites represented < 10% each of total circulating radioactivity. Dasabuvir was cleared mainly through cytochrome P450 mediated oxidation metabolism to M1. M1 and its glucuronide and sulfate conjugates were primarily eliminated in feces. Subsequent oxidation of M1 to the tert-butyl acid, followed by formation of the corresponding glucuronide conjugate, plays a secondary role in elimination. Cytochrome P450 profiling indicated that dasabuvir was mainly metabolized by CYP2C8, followed by CYP3A4. In summary, the biotransformation pathway and clearance routes of dasabuvir were characterized, and the structures of metabolites in circulation and excreta were elucidated. PMID- 27179127 TI - Metabolism and Disposition of the Hepatitis C Protease Inhibitor Paritaprevir in Humans. AB - Paritaprevir (also known as ABT-450), a potent NS3-4A serine protease inhibitor [identified by AbbVie (North Chicago, IL) and Enanta Pharmaceuticals (Watertown, MA)] of the hepatitis C virus (HCV), has been developed in combination with ombitasvir and dasabuvir in a three-direct-acting antiviral agent (DAA) oral regimen for the treatment of patients infected with HCV genotype 1. This article describes the mass balance, metabolism, and disposition of paritaprevir in humans. After the administration of a single 200-mg oral dose of [(14)C]paritaprevir coadministered with 100 mg of ritonavir to four male healthy volunteers, the mean total percentage of the administered radioactive dose recovered was 96.5%, with recovery in individual subjects ranging from 96.0% to 96.9%. Radioactivity derived from [(14)C]paritaprevir was primarily eliminated in feces (87.8% of the dose). Radioactivity recovered in urine accounted for 8.8% of the dose. The biotransformation of paritaprevir in humans involves: 1) P450 mediated oxidation on the olefinic linker, the phenanthridine group, the methylpyrazinyl group, or combinations thereof; and 2) amide hydrolysis at the acyl cyclopropane-sulfonamide moiety and the pyrazine-2-carboxamide moiety. Paritaprevir was the major component in plasma [90.1% of total radioactivity in plasma, AUC from time 0 to 12 hours (AUC0-12hours) pool]. Five minor metabolites were identified in plasma, including the metabolites M2, M29, M3, M13, and M6; none of the metabolites accounted for greater than 10% of the total radioactivity. Paritaprevir was primarily eliminated through the biliary-fecal route followed by microflora-mediated sulfonamide hydrolysis to M29 as a major component in feces (approximately 60% of dose). In summary, the biotransformation and clearance pathways of paritaprevir were characterized, and the structures of metabolites in circulation and excreta were elucidated. PMID- 27179128 TI - Metabolism and Disposition of Pan-Genotypic Inhibitor of Hepatitis C Virus NS5A Ombitasvir in Humans. AB - Ombitasvir (also known as ABT-267) is a potent inhibitor of hepatitis C virus (HCV) nonstructural protein 5A (NS5A), which has been developed in combination with paritaprevir/ritonavir and dasabuvir in a three direct-acting antiviral oral regimens for the treatment of patients infected with HCV genotype 1. This article describes the mass balance, metabolism, and disposition of ombitasvir in humans without coadministration of paritaprevir/ritonavir and dasabuvir. Following the administration of a single 25-mg oral dose of [(14)C]ombitasvir to four healthy male volunteers, the mean total percentage of the administered radioactive dose recovered was 92.1% over the 192-hour sample collection in the study. The recovery from the individual subjects ranged from 91.4 to 93.1%. Ombitasvir and corresponding metabolites were primarily eliminated in feces (90.2% of dose), mainly as unchanged parent drug (87.8% of dose), but minimally through renal excretion (1.9% of dose). Biotransformation of ombitasvir in human involves enzymatic amide hydrolysis to form M23 (dianiline), which is further metabolized through cytochrome P450-mediated oxidative metabolism (primarily by CYP2C8) at the tert-butyl group to generate oxidative and/or C-desmethyl metabolites. [(14)C]Ombitasvir, M23, M29, M36, and M37 are the main components in plasma, representing about 93% of total plasma radioactivity. The steady-state concentration measurement of ombitasvir metabolites by liquid chromatography-mass spectrometry analysis in human plasma following multiple doses of ombitasvir, in combination with paritaprevir/ritonavir and dasabuvir, confirmed that ombitasvir is the main component (51.9% of all measured drug-related components), whereas M29 (19.9%) and M36 (13.1%) are the major circulating metabolites. In summary, the study characterized ombitasvir metabolites in circulation, the metabolic pathways, and the elimination routes of the drug. PMID- 27179129 TI - Bidirectional functions of thrombin on fibrinolysis: Evidence of thrombin dependent enhancement of fibrinolysis provided by spontaneous plasma clot lysis. AB - Besides procoagulant activity, thrombin exhibits anticoagulant and profibrinolytic activities. We demonstrated that the euglobulin clot lysis time (ECLT) was shortened by endogenously generated thrombin as a result of the inactivation of plasminogen activator inhibitor type 1 (PAI-1). In contrast, thrombin suppressed fibrinolytic activity through the activation of thrombin activatable fibrinolysis inhibitor (TAFI). Here, using three different clot lysis assays of the ECLT, the tissue plasminogen activator supplemented plasma clot lysis time (tPA-PCLT) and the spontaneous plasma clot lysis time (s-PCLT), we analyzed how the coagulation process modifies fibrinolysis. The ECLT was shortened by exogenously supplemented thrombin in a dose-dependent manner in the absence of calcium ion (Ca(++)), whereas this shortening was not observed in the presence of Ca(++) where endogenous prothrombin was effectively activated to thrombin. This shortening was also not observed for the tPA-PCLT, in which tPA is supplemented in excess and PAI-1 activity is mostly lost. On the contrary, thrombin dose-dependently prolonged the tPA-PCLT, which was mostly abolished by inhibitors of carboxypeptidase and activated FXIII, suggesting that the prolongation is TAFI- and Factor XIII-dependent. The s-PCLT was shortened when thrombin generation was boosted by supplementing tissue factor and phosphatidylserine together with Ca(++), which was more apparent in the presence of inhibitors of activated FXIII and activated TAFI. Thus, thrombin appeared to express its enhancing effect on fibrinolysis even in plasma, in addition to its inhibiting effect. These bidirectional functions of thrombin on fibrinolysis seem to take place on demand under different environments to maintain adequate vascular blood flow. PMID- 27179130 TI - Hemodynamics associated with atrial fibrillation directly alters thrombotic potential of endothelial cells. AB - An experimental in vitro model of the hemodynamics that occur in atrial fibrillation (AFib) in the left atrial appendage (LAA) was developed to study changes in human endothelial cell thrombotic potential. We applied human-derived sinus rhythm and AFib hemodynamic shear stress patterns to primary human endothelial cells (ECs) in culture. We found that ECs exposed to AFib hemodynamics have increased thrombotic potential as measured by increased expression of pro-thrombotic gene markers and fibrin deposition on the endothelium. Treatment with the factor Xa inhibitor, apixaban, attenuated fibrin deposition thickness while increasing fibrin density at the endothelial cell surface. This study suggests that altered hemodynamics associated with AFib play a key role in driving the thrombotic potential of the LAA endothelium. PMID- 27179131 TI - Direct oral anticoagulant drug level testing in clinical practice: A single institution experience. AB - We performed a review of all direct oral anticoagulant (DOAC) levels - ecarin times for dabigatran and anti-Xa levels for rivaroxaban and apixaban - ordered at our institution with the purpose of evaluating DOAC levels from "real-world" (non clinical trial) patients taking DOACs long-term, in order to assess levels obtained, reasons for checking levels, and actions taken based on the testing result. A total of 28 patients had 48 levels sent over a 36-month period. The majority of outpatient levels were within or close to the range of published values. The setting in which levels were sent influenced how results affected management decisions: in the outpatient setting, the majority of levels served to reassure clinicians that DOAC levels were within expected ranges resulting in continuation of chosen management, whereas in the inpatient setting, DOAC levels were used most frequently to detect DOAC presence in urgent clinical situations and influenced clinical decision-making in the peri-procedural and pre-operative periods. Our results demonstrate that while testing may be useful if immediately available in urgent clinical situations where assessment of drug presence is needed, DOAC level monitoring is infrequently used overall, and the lack of use combined with the paucity of available evidence to guide clinical decision-making based on the results suggests there is little urgency to make the tests widely available for routine use outside of acute settings in the emergency department and urgent surgical setting. PMID- 27179132 TI - Diabetes mellitus, glucose control parameters and platelet reactivity in ticagrelor treated patients. PMID- 27179133 TI - Influence of particulate and dissociated metal-on-metal hip endoprosthesis wear on mesenchymal stromal cells in vivo and in vitro. AB - In hip arthroplasty the implants' articulating surfaces can be made of a cobalt chromium-molybdenum (CoCrMo) alloy. The use of these metal-on-metal (MoM) pairings can lead to the release of wear products such as metallic particles and dissociated metal species, raising concerns regarding their safety amongst orthopedic surgeons and the public. MoM-wear particles are reported to be heterogeneous in their physicochemical properties, are capable of inducing adverse effects on a cellular level and are thought to be involved in relevant clinical problems like aseptic osteolysis. Yet, it remains elusive how MoM-wear affects bone forming cells and their progenitors: bone marrow residing mesenchymal stromal cells (MSCs). This study introduces an assessment of the in vivo exposure to particulate and dissociated Co and Cr and evaluates the effects of MoM-wear on MSCs. The exposure to MoM-wear products in vivo and in vitro leads to a decrease in MSCs' osteogenic matrix mineralization and alkaline phosphatase activity on a cellular and systemic level. In conclusion, MoM-wear products are released in the periprosthetic region and elevate bone marrow Co and Cr concentrations towards levels that impair osteogenic differentiation of MSCs. Therefore, the ongoing use of CoCrMo alloys for articulating surfaces in joint replacement implants needs critical reconsideration. PMID- 27179134 TI - A disposable power source in resource-limited environments: A paper-based biobattery generating electricity from wastewater. AB - We report a novel paper-based biobattery which generates power from microorganism containing liquid derived from renewable and sustainable wastewater which is readily accessible in the local environment. The device fuses the art of origami and the technology of microbial fuel cells (MFCs) and has the potential to shift the paradigm for flexible and stackable paper-based batteries by enabling exceptional electrical characteristics and functionalities. 3D, modular, and retractable battery stack is created from (i) 2D paper sheets through high degrees of folding and (ii) multifunctional layers sandwiched for MFC device configuration. The stack is based on ninja star-shaped origami design formed by eight MFC modular blades, which is retractable from sharp shuriken (closed) to round frisbee (opened). The microorganism-containing wastewater is added into an inlet of the closed battery stack and it is transported into each MFC module through patterned fluidic pathways in the paper layers. During operation, the battery stack is transformed into the round frisbee to connect eight MFC modules in series for improving the power output and simultaneously expose all air cathodes to the air for their cathodic reactions. The device generates desired values of electrical current and potential for powering an LED for more than 20min. PMID- 27179135 TI - Platelike WO3 sensitized with CdS quantum dots heterostructures for photoelectrochemical dynamic sensing of H2O2 based on enzymatic etching. AB - A platelike tungsten trioxide (WO3) sensitized with CdS quantum dots (QDs) heterojunction is developed for solar-driven, real-time, and selective photoelectrochemical (PEC) sensing of H2O2 in the living cells. The structure is synthesized by hydrothermally growing platelike WO3 on fluorine doped tin oxide (FTO) and subsequently sensitized with CdS QDs. The as-prepared WO3-CdS QDs heterojunction achieve significant photocurrent enhancement, which is remarkably beneficial for light absorption and charge carrier separation. Based on the enzymatic etching of CdS QDs enables the activation of quenching the charge transfer efficiency, thus leading to sensitive PEC recording of H2O2 level in buffer and cellular environments. The results indicated that the proposed method will pave the way for the development of excellent PEC sensing platform with the quantum dot sensitization. This study could also provide a new train of thought on designing of self-operating photoanode in PEC sensing, promoting the application of semiconductor nanomaterials in photoelectrochemistry. PMID- 27179136 TI - Nanogold-functionalized g-C3N4 nanohybrids for sensitive impedimetric immunoassay of prostate-specific antigen using enzymatic biocatalytic precipitation. AB - This work reports on a new impedimetric immunosensing strategy for sensitive detection of prostate-specific antigen (PSA) in biological fluids. The assay was carried out on monoclonal anti-PSA capture antibody-modified glassy carbon electrode with a sandwich-type detection format. Gold nanoparticles-decorated g C3N4 nanosheets (AuNP/g-C3N4), synthesized by the wet-chemistry method, were utilized for the labeling of polyclonal anti-PSA detection antibody and horseradish peroxidase (HRP). Upon target PSA introduction, the sandwiched immunocomplex could be formed between capture antibody and detection antibody. Followed by the AuNP/g-C3N4, the labeled HRP could catalyze 4-choloro-1-naphthol into benzo-4-chlorohexadienone. The as-generated insoluble product was coated on the electrode surface, thus increasing the Faradaic impedance of Fe(CN)6(4-/3)(-) indicator between the solution and the base electrode. Under the optimal conditions, the impedance increased with the increasing target PSA in the sample, and exhibited a wide linear range from 10pgmL(-1) and 30ngmL(-1) with a detection limit of 5.2pgmL(-1). A repeatability and intermediate precision of <14% was accomplished. The specificity and method accuracy in comparison with commercial PSA ELISA kit for analysis of human serum specimens were relatively satisfactory. PMID- 27179137 TI - The impact of children's exposure to greenspace on physical activity, cognitive development, emotional wellbeing, and ability to appraise risk. AB - INTRODUCTION: The current study utilised objective techniques to investigate the relationship between children's time spent in greenspace (open land covered in grass or other vegetation) with various physical and psychological variables. Potential relationships between physical activity and greenspace with body composition, emotional wellbeing, sensation seeking tendencies, ability to appraise risk, and cognitive development are investigated. METHODS: 108 participants aged 11-14 years from three intermediate schools in Auckland, New Zealand, were assessed. Moderate-to-vigorous physical activity (MVPA) and geolocational data were recorded using accelerometers and portable global positioning system (GPS) receivers (respectively) over a 7-day period in September-December 2014. Body mass index (BMI) and waist-to-height ratio (WHtR) were calculated from height, weight, and waist circumference. Participants also completed online cognitive testing, a computerised risk appraisal tool, and a questionnaire for assessing emotional wellbeing and sensation seeking characteristics. Data analysis took place during February to May 2015. Generalised linear mixed models were used to quantify the associations between MVPA, greenspace exposure, and secondary outcome variables. RESULTS: Findings confirmed that greenspace exposure is positively associated with MVPA in children (B=0.94; p<0.05). Furthermore, both greenspace exposure and MVPA were related to greater emotional wellbeing, with the former exhibiting a stronger relationship than the latter. Risk-taking and sensation seeking scores were positively associated with MVPA, but not with greenspace exposure. No associations were detected between BMI, WHtR, cognitive domains, and either MVPA or greenspace exposure. CONCLUSIONS: Findings support the theory that for children, greenspaces are an important environmental influence on physical activity and emotional wellbeing. PMID- 27179138 TI - Where are the schools? Children, families and food practices. AB - Reducing childhood obesity is an international priority and children's diets, food knowledge and practices have come under intense scrutiny in both policy and popular discourse. Notwithstanding evidence that health interventions which resonate with children's own views are the most effective, there is still relatively little research which mobilises children's everyday perspectives on food to inform public health policy. We report key findings from a qualitative study with 53 children aged 9-10, attending two socio-economically contrasting schools in the UK. The study explored children's understandings of food in everyday life and their ideas about the relationship between food and health. Throughout the study, despite recent attempts to position schools as key sites for public health interventions, children consistently emphasised families as the locus for enduring food practices. The research highlights the value of listening to children and applying our understanding of their perspectives to ensure that public health initiatives work with the important influences on their diet and health that they themselves identify. PMID- 27179139 TI - Serum concentrations of fibroblast growth factor 21 are elevated in patients with congenital or acquired lipodystrophy. AB - OBJECTIVE: Patients with lipodystrophy (LD) suffer from loss of subcutaneous adipose tissue accompanied by dysregulation of several adipocyte-secreted factors. However, regulation of adipocyte-expressed fibroblast growth factor (FGF) 21 which acts in an insulin-mimetic, lipid-lowering, and anti-atherogenic manner has not been investigated in non-human immunodeficiency virus (HIV) LD. MATERIAL AND METHODS: Circulating serum FGF21 levels were quantified in 37 patients with non-HIV LD and 37 controls matched for age, gender, and body mass index. Moreover, FGF21 plasma levels and mRNA expression were measured in LD mice and control animals. Additionally, serum FGF21 levels were assessed in 10 LD patients before and during metreleptin therapy. RESULTS: Median FGF21 serum concentrations were significantly higher in LD patients (381.2ng/l) as compared to the control group (231.2ng/l; p=0.023). There was an independent and positive association between circulating FGF21 and serum triglycerides (TG), as well as fibrate treatment, in multiple linear regression analysis. LD mice showed significantly upregulated FGF21 plasma levels (4.5-fold), as well as mRNA expression in various adipose tissue depots and liver as compared to controls (p<0.05). Metreleptin treatment did not significantly alter circulating FGF21 levels in human subjects. CONCLUSIONS: Serum concentrations of FGF21 are elevated in patients with non-HIV LD with adipose tissue and liver being potential sources of increased production. TG and fibrate treatment are independent positive predictors of circulating FGF21. PMID- 27179140 TI - Toll-like receptor 2 signalling: Significance in megakaryocyte development through wnt signalling cross-talk and cytokine induction. AB - TLR2 is a toll-like receptor protein which is involved in innate immune responses. TLR2 recognize several virus, fungal and bacterial pathogens, upon their uptake cause internalization and cellular activation. During this process several cytokines participate including interleukins, IL6 and IL12. Interestingly, TLR2 is expressed on megakaryocytes (MKs) and platelets, which is crucial for immune mediated platelet activation. The role of TLR2 on MKs is not completely understood. We observed TLR2 induction leads to MK maturation and is involved in production of ROS which is essential for MK development. In Dami cells, TLR2 up-regulation causes increase in the cytokine production, particularly IL-6, which has been shown to stimulate CFU formation and CD41 expression. Additionally, TLR2 ligand induces wnt beta-catenin signalling pathway components suggesting a cross talk between wnt and TLR pathway leading to maturation of MKs. This study shows TLR2 signalling induce cytokine production and regulate wnt signalling thereby cause maturation of MKs. PMID- 27179141 TI - Dispersion relations of elastic waves in one-dimensional piezoelectric/piezomagnetic phononic crystal with functionally graded interlayers. AB - The effects of functionally graded interlayers on dispersion relations of elastic waves in a one-dimensional piezoelectric/piezomagnetic phononic crystal are studied in this paper. First, the state transfer equation of the functionally graded interlayer is derived from the motion equation by the reduction of order (from second order to first order). The transfer matrix of the functionally graded interlayer is obtained by solving the state transfer equation with the spatial-varying coefficient. Based on the transfer matrixes of the piezoelectric slab, the piezomagnetic slab and the functionally graded interlayers, the total transfer matrix of a single cell is obtained. Further, the Bloch theorem is used to obtain the resultant dispersion equations of in-plane and anti-plane Bloch waves. The dispersion equations are solved numerically and the numerical results are shown graphically. Five kinds of profiles of functionally graded interlayers between a piezoelectric slab and a piezomagnetic slab are considered. It is shown that the functionally graded interlayers have evident influences on the dispersion curves and the band gaps. PMID- 27179142 TI - Optimization of machining and vibration parameters for residual stresses minimization in ultrasonic assisted turning of 4340 hardened steel. AB - The residual stresses generated in the machined work piece have detrimental effect on fatigue life, corrosion resistance and tribological properties. However, the effect of cutting and vibration parameters on residual stresses in Ultrasonic Assisted Turning (UAT) has not been dealt with. The present paper highlights the effect of feed rate, depth of cut, cutting velocity and percentage intensity of ultrasonic power on residual stress generation. XRD analysis has been carried out to measure the residual stress while turning 4340 hardened steel using UAT. The experiments were performed based on response surface methodology to develop statistical model for residual stress. The outcome of ANOVA revealed that percentage intensity and feed rate significantly affect the residual stress generation. The significant interactions between process parameters have also been presented tin order to understand the thermo-mechanical mechanism responsible for residual stress generation. PMID- 27179143 TI - Recent technological advancements in breast ultrasound. AB - Ultrasound is becoming increasingly common as an imaging tool for the detection and characterization of breast tumors. This paper provides an overview of recent technological advancements, especially those that may have an impact in clinical applications in the field of breast ultrasound in the near future. These advancements include close to 100% fractional bandwidth high frequency (5-18MHz) 2D and 3D arrays, automated breast imaging systems to minimize the operator dependence and advanced processing techniques, such as those used for detection of microcalcifications. In addition, elastography and contrast-enhanced ultrasound examinations that are expected to further enhance the clinical importance of ultrasound based breast tumor screening are briefly reviewed. These techniques have shown initial promise in clinical trials and may translate to more comprehensive clinical adoption in the future. PMID- 27179144 TI - Reinforcement of freeze-dried chitosan scaffolds with multiphasic calcium phosphate short fibers. AB - The composite scaffolds of the chitosan and multiphasic calcium phosphate (HW) short fibers were prepared by freeze drying and characterized by X-ray diffractometry (XRD), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM and FE-SEM). The mechanical properties of the scaffolds were assessed by compression test. The incorporation of HW fibers consisting three phases of hydroxyapatite (HA), beta-tricalcium phosphate (beta-TCP) and calcium pyrophosphate (CPP) into the chitosan matrices was associated with an increase in pore size, density and compressive strength and modulus, and a decrease in porosity and swelling ratio of the scaffolds. The strongest composite scaffolds in this study with a chitosan: HW fibers weight ratio of 1:1 showed a mean porosity of 69% and a mean strength and modulus of 420kPa and 3.87MPa, respectively. The in vitro bioactivity of the composites was confirmed by the formation of a calcium phosphate rich layer on the surface of soaked scaffolds in simulated body fluid. The findings of this initial work indicate that the chitosan-multiphasic calcium phosphate short fibers may be a suitable material for bone scaffolding. PMID- 27179146 TI - The doctor-patient relationship as a toolkit for uncertain clinical decisions. AB - Medical uncertainty is a well-recognized problem in healthcare, yet how doctors make decisions in the face of uncertainty remains to be understood. This article draws on interdisciplinary literature on uncertainty and physician decision making to examine a specific physician response to uncertainty: using the doctor patient relationship as a toolkit. Additionally, I ask what happens to this process when the doctor-patient relationship becomes fragmented. I answer these questions by examining obstetrician-gynecologists' narratives regarding how they make decisions when faced with uncertainty in childbirth. Between 2013 and 2014, I performed 21 semi-structured interviews with obstetricians in the United States. Obstetricians were selected to maximize variation in relevant physician, hospital, and practice characteristics. I began with grounded theory and moved to analytical coding of themes in relation to relevant literature. My analysis renders it evident that some physicians use the doctor-patient relationship as a toolkit for dealing with uncertainty. I analyze how this process varies for physicians in different models of care by comparing doctors' experiences in models with continuous versus fragmented doctor-patient relationships. My key findings are that obstetricians in both models appealed to the ideal of patient centered decision-making to cope with uncertain decisions, but in practice physicians in fragmented care faced a number of challenges to using the doctor patient relationship as a toolkit for decision-making. These challenges led to additional uncertainties and in some cases to poor outcomes for doctors and/or patients; they also raised concerns about the reproduction of inequality. Thus organization of care delivery mitigates the efficacy of doctors' use of the doctor-patient relationship toolkit for uncertain decisions. These findings have implications for theorizing about decision-making under conditions of medical uncertainty, for understanding how the doctor-patient relationship and model of care affect physician decision-making, and for forming policy on the optimal structure of medical work. PMID- 27179145 TI - Monitoring 3D dose distributions in proton therapy by reconstruction using an iterative method. AB - The Bragg peak of protons can be determined by measuring prompt gamma-rays. In this study, prompt gamma-rays detected by single-photon emission computed tomography with a geometrically optimized collimation system were reconstructed by an iterative method. The falloff position by iterative method (52.48mm) was most similar to the Bragg peak (52mm) of an 80MeV proton compared with those of back-projection (54.11mm) and filtered back-projection (54.91mm) methods. Iterative method also showed better image performance than other methods. PMID- 27179147 TI - Identification of meat species by using laser-induced breakdown spectroscopy. AB - The aim of the present study is to identify meat species by using laser-induced breakdown spectroscopy (LIBS). Elemental composition differences between meat species were used for meat identification. For this purpose, certain amounts of pork, beef and chicken were collected from different sources and prepared as pellet form for LIBS measurements. The obtained LIBS spectra were evaluated with some chemometric methods, and meat species were qualitatively discriminated with principal component analysis (PCA) method with 83.37% ratio. Pork-beef and chicken-beef meat mixtures were also analyzed with partial least square (PLS) method quantitatively. Determination coefficient (R(2)) and limit of detection (LOD) values were found as 0.994 and 4.4% for pork adulterated beef, and 0.999 and 2.0% for chicken adulterated beef, respectively. In the light of the findings, it was seen that LIBS can be a valuable tool for quality control measurements of meat as a routine method. PMID- 27179149 TI - Halal stunning and slaughter: Criteria for the assessment of dead animals. AB - The debate surrounding the acceptability of stunning for Halal slaughter is one that is likely to linger. Compared to a couple of decades or so ago, one may argue that pre-slaughter stunning is becoming a popular practice during Halal slaughter due to the increasing number of Muslim-majority countries who continue to issue religious rulings (Fatwa) to approve the practice. Concerns have often, however been raised about the likelihood of some animals dying as a result of stunning and whether there are mechanisms in place to identify and remove dead animals stunned with irreversible techniques before their necks are cut. This paper reviews literature about what makes meat Halal, considers the arguments put forward by proponents and opponents of pre-slaughter stunning for Halal production and examines the criteria used by Halal Certification Bodies to identify and reject animals that may die as a result of irreversible stunning and considers the specific risks of waterbath stunning (for poultry) from a Halal viewpoint. PMID- 27179148 TI - Study of modified atmosphere packaging on the quality of ozonated freeze-dried chicken meat. AB - The objective of this study was to evaluate the effects of different modified atmosphere packaging (MAP) conditions on the physicochemical and sensory properties of ozonated freeze-dried chicken meat stored at 21+/-1 degrees C for 28days. To this end, 14 MAP treatments were performed to obtain the most suitable packaging atmosphere. High concentrations of O2 in MAP promoted loss of redness and increased the pH values. Moreover, when the concentration of CO2 in MAP was more than 40%, high values of textural parameters and low scores of sensory hardness and chewiness were achieved. The 20%CO2/80%N2 gas combination was found to be the most effective treatment for best maintaining the physicochemical and sensory quality of ozonated dried chicken samples similar to that of raw meat. PMID- 27179150 TI - Increased ongoing neural variability in ADHD. AB - Attention Deficit Hyperactivity Disorder (ADHD) has been described as a disorder where frequent lapses of attention impair the ability of an individual to focus/attend in a sustained manner, thereby generating abnormally large intra individual behavioral variability across trials. Indeed, increased reaction time (RT) variability is a fundamental behavioral characteristic of individuals with ADHD found across a large number of cognitive tasks. But what is the underlying neurophysiology that might generate such behavioral instability? Here, we examined trial-by-trial EEG response variability to visual and auditory stimuli while subjects' attention was diverted to an unrelated task at the fixation cross. Comparisons between adult ADHD and control participants revealed that neural response variability was significantly larger in the ADHD group as compared with the control group in both sensory modalities. Importantly, larger trial-by-trial variability in ADHD was apparent before and after stimulus presentation as well as in trials where the stimulus was omitted, suggesting that ongoing (rather than stimulus-evoked) neural activity is continuously more variable (noisier) in ADHD. While the patho-physiological mechanisms causing this increased neural variability remain unknown, they appear to act continuously rather than being tied to a specific sensory or cognitive process. PMID- 27179151 TI - Reduced sensitivity to contrast signals from the eye region in developmental prosopagnosia. AB - Contrast-related signals from the eye region are known to be important for the processing of facial identity. Individuals with developmental prosopagnosia (DP) have severe face recognition problems, which may be linked to deficits in the perceptual processing of identity-related information from the eyes. We tested this hypothesis by measuring N170 components in DP participants and age-matched controls in response to face images where the contrast polarity of the eyes and of other face parts was independently manipulated. In different trials, participants fixated either the eye region or the lower part of a face. In the Control group, contrast-reversal of the eyes resulted in enhanced and delayed N170 components, irrespective of the contrast of other face parts and of gaze location. In the DP group, these effects of eye contrast on N170 amplitudes were strongly and significantly reduced, demonstrating that perceptual face processing in DP is less well tuned to contrast information from the eye region. Inverting the contrast of other parts of the face affected N170 amplitudes only when fixation was outside the eye region. This effect did not differ between the two groups, indicating that DPs are not generally insensitive to the contrast polarity of face images. These results provide new evidence that a selective deficit in detecting and analysing identity-related information provided by contrast signals from the eye region may contribute to the face recognition impairment in DP. PMID- 27179152 TI - Posterior cruciate ligament tears in Taiwan: an analysis of 140 surgically treated cases. AB - INTRODUCTION: Posterior cruciate ligament (PCL) tears are commonly due to motor vehicle accidents or sports-related trauma but can differ geographically. We report the various causes, types, and associated injuries of PCL tears in Taiwan. METHODS: One hundred forty patients with arthroscopically treated PCL tears were reviewed. RESULTS: Scooter-related trauma was the most common cause of PCL tear in our series and is typically an isolated ligamentous injury. High-velocity motor vehicle accidents accounted for a small percentage of PCL tears. CONCLUSION: Scooter-related PCL tears are common in Taiwanese patients and are often isolated ligamentous injuries similar to low-velocity sports-related PCL injuries. PMID- 27179153 TI - Imaging findings of spinal brown tumors: a rare but important cause of pathologic fracture and spinal cord compression. AB - Brown tumors rarely develop in the spine, and neurological compromise is exceedingly uncommon. There is a growing body of literature describing brown tumors that involve the spine, but few emphasize the radiographic findings. In the present case, we illustrate the development and progression of biopsy-proven brown tumors leading to neurological compromise through radiographs, computed tomography, magnetic resonance, and nuclear imaging acquired over a 4-year span. PMID- 27179154 TI - Efficacy of single voxel 1H MR spectroscopic imaging at 3T for the differentiation of benign and malign breast lesions. AB - PURPOSE: The aim of our study was to evaluate the effect of 1H Magnetic Resonance Spectroscopy (MRS) in differentiating breast lesions. MATERIALS AND METHODS: Single voxel 1H Magnetic Resonance Spectroscopy (1H-MRS) was performed with 3T magnet in 45 women. The choline cut off point was set semi-quantitavely. Sensitivity, specificity and accuracy of MRS were calculated. RESULTS: Twenty four of 25 (96%) malignant and 9 of 26 (35%) benign lesions had choline peak. With the use cutoff value of 19,5 MRS provided a 96% sensitivity, 65% specificity and 80% accuracy. CONCLUSION: MRS has a high diagnostic accuracy in differentiating breast lesions. PMID- 27179155 TI - Peritoneal lymphomatosis confused with peritoneal carcinomatosis due to the previous history of gastric cancer: a case report. AB - Peritoneal lymphomatosis is a very rare disease of extranodal involvement of malignant lymphoma that is occasionally confounded with other peritoneal diseases. Herein, we reported the case of a 59-year-old woman who presented with massive ascites with prior history of stomach perforation during endoscopic procedure to treat early gastric cancer. Imaging studies showed massive ascites and tumor infiltration in the omentum and peritoneal wall. Initially, relapsed gastric cancer with peritoneal seeding was suspected based on the patient's history and imaging findings. However, final diagnosis was confirmed by ascites cytology as peritoneal lymphomatosis of diffuse large B-cell lymphoma unlike prior clinical information. PMID- 27179156 TI - Inverted Meckel diverticulum as a lead point of small bowel intussusception: misinterpreting case as a lipoma. AB - Inverted Meckel diverticulum is an uncommon cause of intussusception in adults. It may be confused for an intraluminal lipoma. We present a case of small bowel intussusception due to inverted Meckel diverticulum with characteristic computed tomography finding potentially distinguishable from lipoma. PMID- 27179157 TI - Primary extraskeletal Ewing sarcoma of the stomach: a rare disease in an uncommon location. AB - We report the case of a 63-year-old female undergoing evaluation of symptomatic anemia, gastroesophageal reflux disease, and abdominal pain. After a thorough diagnostic workup, a large, ulcerated mass was identified in the patient's stomach, and surgical pathology in combination with molecular analysis yielded a diagnosis of primary extraskeletal Ewing sarcoma. In our report, we discuss the epidemiologic, clinicopathologic, and radiographic features of this rare disease and provide a review of the existing literature. PMID- 27179158 TI - Improving diagnosis of atraumatic splenic lesions, Part III: malignant lesions. AB - Focal atraumatic splenic lesions often pose a diagnostic challenge on cross sectional imaging. They can be categorized based on etiology, as nonneoplastic, benign neoplastic, and malignant neoplastic (discussed in Part III) lesions, or on prevalence, as common, uncommon, and rare lesions. Familiarity with pertinent clinical parameters, etiology, pathology, prevalence, and ancillary features such as splenomegaly, concomitant hepatic involvement, and extrasplenic findings, in addition to knowledge of imaging spectra of the lesions, can improve diagnostic confidence. Consideration of these factors together can arm the radiologist with the necessary tools to render a more confident diagnosis and thus better aid management. PMID- 27179160 TI - The radiologic diagnosis of idiopathic myointimal hyperplasia of mesenteric veins with a novel presentation: case report and literature review. AB - Idiopathic myointimal hyperplasia of mesenteric veins (IMHMV) is a rare condition of the rectosigmoid colon that primarily affects middle-aged men. IMHMV typically presents as proctosigmoiditis and often requires surgical resection due to complications throughout the protracted clinical course. It can be differentiated from idiopathic chronic inflammatory bowel disease by histopathologic examination of surgically resected colon specimens. This report describes a rare case of IMHMV presenting as left hemicolitis in a 64-year-old male. We also describe potentially distinguishing computed tomographic and angiographic findings that may aid in the diagnosis of IMHMV. PMID- 27179159 TI - Incidence and pathology of repeat CT abdomen and pelvis in an adult emergency department population. AB - INTRODUCTION: Our objective was to identify the incidence of adult patients who undergo more than one computed tomography (CT) abdomen and pelvis within 1 year and detect the incidence of significant pathology on these repeat scans. METHODS: All adults with an initial CT within 12 months and then during an emergency department visit were retrospectively identified. RESULTS: A percentage of 21.1 of the repeat CT scans were positive. Approximately 20% of positive repeat CT scans occurred within the first month and nearly 70% within 6 months of the initial CT scan. CONCLUSIONS: Many patients undergo multiple CT scans within a 1 year time frame with significant pathology identified. PMID- 27179161 TI - Combination of Serum Interleukin-1beta and 6 Levels in the Diagnosis of Perinatal Asphyxia. AB - BACKGROUND: Perinatal asphyxia is an important cause of death, as well as permanent neurological and developmental complications. Diagnosing in time would lead to better prognosis and applying the most proper treatment. We sought to define the predictive values of serum concentrations of interleukin-1beta (IL 1beta) and interleukin-6 (IL-6) in newborns with perinatal asphyxia to see if there is a relation between the short-term neurological deficit and serum IL 1beta and IL-6 concentrations. METHODS: This was a prospective (case-control) study conducted between March 2006 and April 2013, at the Neonatal Intensive Care Unit, Mashhad, Iran. Serum IL-1beta and IL-6 levels were measured at birth in 38 consecutive uninfected neonates with perinatal asphyxia (blood pH < 7.2, low Apgar score, signs of fetal distress) and 47 randomly selected healthy newborns. The results were compared between the groups, using Chi-Square, t-tests, and Mann Whitney tests, as well as receiver operator characteristics (ROC) curves and regression models. RESULTS: Serum IL-1beta and IL-6 concentrations in the infants who developed perinatal asphyxia were significantly higher compared to values in the normal infants [16.88 vs 3.34 pg/mL for IL-1beta, (P = 0.006), and 88.15 vs 6.74 pg/ mL for IL-6, (P < 0.001) respectively]. The sensitivity and specificity for the diagnosis of perinatal asphyxia using serum IL-6 were 80.5% and 81.6% respectively. The sensitivity and specificity using serum IL-1beta were 71% and 89.1%, respectively. CONCLUSION: Evaluating serum IL-6 and 1beta simultaneously, could improve the sensitivity and specificity of early diagnosis of the perinatal asphyxia. The most appropriate indicator of perinatal asphyxia is combined measurement of interleukin 1beta and interleukin 6. PMID- 27179162 TI - Complication of Stenting in Intracranial Arterial Stenosis. AB - INTRODUCTION: To evaluate the perioperative complications and long-term restenosis rates following percutaneous transluminal angioplasty and stenting (PTAS) in patients with intracranial atherosclerotic stenosis (ICAS). METHODS: A retrospective analysis was performed on the clinical data of 102 ICAS patients (103 cases of stenosis) who underwent PTAS. The perioperative complications and long-term restenosis rates were analyzed. RESULTS: The success rate of PTAS was 100%. Six patients (5.83%, 6/103) had perioperative complications. Six cases (6.52%, 6/92) of restenosis occurred and one patient (1.09%) died. Five of the 6 restenosis cases (5.43%) occurred in the blood-supplying region and were associated with ischemic symptoms and one patient (1.09%) had no ischemic symptom. The postoperative restenosis rates at 6, 6 - 12, and 12 - 74 months were 3.26%, 2.56%, and 2.38%, respectively. The postoperative restenosis rates had a significant difference between the residual stenosis rate >= 20% and < 20% (P < 0.05), and between postoperative regular medication and non-regular medication (P < 0.05). The postoperative restenosis risk in patients with age >= 60 years was 13.481 times to that in patients with age < 60 years. The postoperative restenosis risk in patients with residual stenosis rate < 20% was 31.25 times to that in patients with residual stenosis rate >= 20%. The postoperative restenosis risk in patients with regular medication was 12.65 times to that in patients without regular medication. CONCLUSIONS: The vasospasm, arterial dissection, arterial occlusion and acute thrombosis are common perioperative complications following PTAS in patients with ICAS. The medium- and long-term postoperative restenosis rate is low. Age is the risk factor for postoperative restenosis. PMID- 27179163 TI - Transcutaneous Bilirubinometry in Preterm and Term Newborn Infants before and during Phototherapy. AB - INTRODUCTION: To evaluate the accuracy of transcutaneous bilirubin measurement in a large population of newborn infants, before and during the phototherapy. PATIENTS AND METHODS: A single Bilicheck instrument was used for transcutaneous measurements. A photo-opaque patch was positioned over the measurement site prior to starting phototherapy. Transcutaneous bilirubinometry was conducted on an unpatched area of the forehead skin and on the nearby site covered by the photo opaque patch. Readings were obtained from patched and unpatched areas and simultaneous total serum bilirubin concentrations were compared. RESULTS: We studied 134 term and 36 preterm newborns. Pre-phototherapy measurements showed a strong correlation (r: 0.929, P < 0.001, Limit of agreement: -1.8 to 3.1) between Bilicheck and serum bilirubin readings. Post-phototherapy correlation between Bilicheck and serum bilirubin readings was (r: 0.921, P < 0.001, LOA: -1.8 to 2.8) among term and (r: 0.887, P = 0.001, LOA: -1.4 to 2.7) among preterm neonates in patched areas. These correlations were (r: 0.666, P < 0.001, LOA: 1.7 to 7.3) among term and (r: 0.756, P < 0.001, LOA: -0.5 to 5.3) preterm neonates post-phototherapy in unpatched areas. CONCLUSION: BiliCheck can be safely used for the evaluation of bilirubin levels in preterm and term newborn infants under phototherapy. BiliCheck is slightly less reliable among preterm newborns. PMID- 27179164 TI - The Burden of HIV in Iran: Insights from the Global Burden of Disease Study 2010. AB - OBJECTIVES: To evaluate the HIV/AIDS burden in Iran from 1980 to 2010 using the Global Burden of Disease Study 2010 (GBD 2010). METHODS: The burden of HIV/AIDS in Iran was obtained from a systematic study from 1990 to 2010 by the GBD team. The GBD 2010 disability weights were used to calculate the HIV/AIDS Disability Adjusted Life Years (DALY) based on the HIV prevalence reported by the Joint United Nations Program on HIV/AIDS (UNAIDS) estimation. Mortality data were obtained from the vital registration and statistics system of Iran. In the current study, the results are discussed, and the potential solutions are provided for observed deficiencies. RESULTS: HIV/AIDS-related DALYs (3.6 per 100,000 in 1990, and 154 per 100,000 in 2010) and death (0.07 per 100,000 in 1990, and 3 per 100,000 in 2010) had increased in Iran from 1990 to 2010. The majority of individuals who died of HIV were between 15 to 49 years old. The estimated rank of HIV/AIDS burden compared with the burden of other leading disease was 152nd in 1990 and considerably increased to 37th in 2010 in Iran. CONCLUSION: Since the majority of HIV/AIDS DALYs and deaths occur among young people, the burden of HIV/AIDS still remains high in Iran. Due to the limitations of the GBD study, National and Sub-National Burden of Diseases (NASBOD) study is being conducted in Iran to calculate the burden of diseases, including HIV/AIDS. PMID- 27179165 TI - Assessment the Efficiency of the Constructed Minigenome of Rabies Virus using PV Strain as Helper Virus. AB - INTRODUCTION: Rabies is an acute viral disease that causes encephalomyelitis in mammals and human. The only way to prevent this disease is through vaccination before or after exposure. The aim of this study is to evaluate the efficiency of the Pasteur virus (PV) minigenome, using PV strain. MATERIALS AND METHODS: Enhanced Green Fluorescent Protein (EGFP) sequence was placed between the designed necessary elements (Hammerhead, HDV ribozyme, 3' Leader, and 5' Trailer sequences), which resemble the rabies virus PV strain (PV2061) genome and anti genome. These constructs were placed between T7 polymerase promoter and T7 polymerase terminator sequences. The accuracy of the minigenome was confirmed by the expression of EGFP using the helper virus in T7-BHK cell line. RESULTS: The viral necessary elements of positive and negative sense strands were evaluated for the ability of EGFP expression in the presence of the helper virus. While the positive strand showed background results, no EGFP background was observed in the negative strand application. CONCLUSION: Establishment of minigenome system does not require advanced biosafety levels. Furthermore, using minigenome system eliminates many potential confounding factors that may be present in coding regions of the genome. Use of the minigenome system is easier and more feasible than the full genome rescue of the virus. This study successfully shows the efficiency of the constructed rabies virus minigenome in expression of inserted gene. PMID- 27179166 TI - Effect of Omega-3 PUFAs Supplementation with Lifestyle Modification on Anthropometric Indices and Vo2 max in Overweight Women. AB - BACKGROUND: Despite the fact that the recommendations of counteracting obesity advocate for changing lifestyle and physical activity habits, the prevalence of obesity continues to rise. The aim of the study was to investigate the effect of omega-3 PUFAs supplementation with lifestyle modification on anthropometric indices and Vo2max in overweight women. METHODS: Fifty overweight women aged between 20 to 45 years were recruited in this interventional study. Women randomly were divided into two experimental groups (n = 25). Group 1 received omega-3 supplement, aerobic exercise program, and a healthy diet education. Group 2 was similar to group 1, except in that patients received placebo instead of omega-3 capsules. Experimental and placebo group subjects were asked to take one supplementary capsule every day, for 8 weeks. Anthropometric indices were measured in the fourth and eighth weeks of the trial. The maximum aerobic capacity (Vo2max) was determined using a gas analysis device. The level of significance for comparing the results before and after the trial was considered at P < 0.05. RESULTS: According to the data, body weight, body fat percentage, waist circumference, and abdominal skinfold thickness significantly reduced in the omega-3 treated group compared to the control group during 8 weeks after the initiation of the study (P < 0.05). In addition, supplementation of omega-3, significantly improved the VO2max outcome compared to that of the control group (P = 0.03). CONCLUSION: According to the results, it seems that omega-3 PUFAS supplementation with lifestyle modification has positive effects on anthropometric indices and Vo2max in overweight women. PMID- 27179167 TI - Effects of Radio Frequency and Ultrasound Cavitation Therapy on Serum C-reactive Protein and Pro-oxidant-Antioxidant Levels. AB - BACKGROUND: A combination of radio-frequency (RF) and ultrasound cavitation (UC) has been reported to reduce indices of obesity. In this study, we aimed to investigate the effect of a combination of these techniques on anthropometric indices, pro-oxidant-antioxidant balance (PAB), and serum high-sensitivity C reactive protein (hs-CRP). MATERIALS AND METHODS: This randomized clinical trial was performed on 50 healthy women between January 2014 and June 2014 in Ghaem Hospital, Mashhad, Iran. Participants were randomized to one of two groups, both of which received a low-calorie diet containing 500-kcal energy deficit per day. The trial group included twenty-five subjects who were assigned to the combined treatment of RF and ultrasound cavitation program of abdomen and flank areas. There were twenty-five control subjects who received the low calorie diet alone. Biochemical markers, including serum hs-CRP and PAB values, and anthropometric indices were measured in the intervention group and healthy controls. RESULTS: For both the intervention and control groups, waist circumference was reduced significantly by 3.76 +/- 1.69 and 2.40 +/- 1.04, respectively (P < 0.05). In addition, abdominal circumference was reduced by 9.5 +/- 2.66 and 3.12 +/- 1.88, in these groups, respectively (P < 0.001). Decrement of PAB level in the intervention group, and its increment in the control group, were not significant (P > 0.05). In addition, reductions of hs-CRP and PAB between the two studied groups during five weeks of study were not significant (P > 0.05). CONCLUSION: Although there were significant reductions in anthropometric indices following treatment with RF and UC, the effects on serum PAB or hs-CRP were no significantly different, compared to the control group. Further studies are needed to confirm the beneficial effect for the use of these techniques. PMID- 27179168 TI - Association of the Exotoxin A and Exoenzyme S with Antimicrobial Resistance in Pseudomonas Aeruginosa Strains. AB - INTRODUCTION: Pseudomonas aeruginosa is a gram-negative and opportunistic bacterium that causes opportunistic infections in immunosuppressed patients. The main purpose of this study was to investigate the association between exotoxin A and exoenzyme S production with antibiotic resistance patterns. METHODS: The toxA and exoS genes were detected in 102 clinical isolates by PCR. Antibiotic susceptibility tests were performed by disk diffusion method (Kirby Bauer). The Chi-square and Fisher's test were used for evaluation of the association between "toxins and infections source" and "toxins and antibiotic resistance" respectively. RESULTS: Frequency of toxA+ and exoS+ strains was 81% and 61%, respectively. The association between drug resistance and toxA+ genotype was significant for all antibiotics tested (P < 0.05) except aztreonam; however, no significant association was observed between drug resistance and exoS gene (P > 0.05). CONCLUSIONS: High frequency of toxA+ resistant strains isolated from inpatients and significant association between the toxin and drug resistance in more antibiotics, reinforces possible role of exotoxin A as an extracellular protein in the regulation of drug resistance genes. The results may be further verified by Southern blot analysis of toxA and exoS gene expression and elucidation of the mechanism of antibiotic resistance. PMID- 27179169 TI - Role of Vitamin D in Cardiovascular Disease. AB - BACKGROUND: According to many studies, vitamin D deficiency has been linked to cardiovascular diseases (CV). Other than maintaining skeletal health, vitamin D has been shown to decrease the risk of developing CV disease such as hypertension, coronary artery disease (CAD) and thromboembolism. MATERIALS AND METHODS: To perform a comprehensive review of the current literature on vitamin D and CV disease, we searched the online database, including PUBMED, Scopus, and Google Scholar until data inception January 2016. The search term included "vitamin D", "blood pressure", "hypertension", "coronary artery disease "and "thrombosis". We only included human studies that were published in English. RESULTS: A majority of data indicate that there is no relationship between vitamin D and hypertension, but the association of vitamin D with thrombosis is yet to be determined. Vitamin D is a fair predictor of adverse outcomes in coronary artery disease (CAD), which highlights it for future studies. CONCLUSION: According to research, there is a high prevalence of vitamin D deficiency among patients with CV diseases, which needs to be diagnosed and treated. PMID- 27179170 TI - Genetic Studies in Intellectual Disability and Behavioral Impairment. AB - Intellectual Disability (ID, also known as mental retardation) is a debilitating neurodevelopmental disorder affecting nearly 1% of the general population worldwide. Occurrence of behavioral disorders in individuals with ID is four times higher than that in the general population. An increasing number of studies seek to find a common pathway to elucidate brain structure/function and its contribution to behavior. This article deals with different behavioral disorders reported in individuals with syndromic and non-syndromic ID and possible candidate genes, most of which are involved in synaptic formation and function. Many ID cases with behavior impairments were referred to genetic centers to identify genetic causes; Therefore, the authors gathered data from their own studies along with similar published reports, to provide a review on genes involved in brain development and cognition. In this study, we argued how defects in genes with diverse functional role may contribute to behavior impairments and a brain malfunction. Evidences from individual with cognitive impairment as well as murine and drosophila animal models have been used to show behavioral consequences of functional deficits in genes speculated to play a role in cognition and learning. PMID- 27179171 TI - Left Inguinal Bladder Hernia that Causes Dilatation in the Ureter. AB - The scrotal bladder hernia is a rare condition that may present as scrotal swelling and urinary system obstruction or infection symptoms. Diagnosis of this condition before the operation decreases the severe complications like bladder injury during operation. In this article, a 75-year-old man presented to our clinic with right inguinal swelling and lower urinary system infection. Inguinal bladder hernia was diagnosed after performing a computed tomography. The hernia was repaired without any complications. PMID- 27179172 TI - A Clone with 5, 17 and 18 Monosomies as Stemline in a Patient with De novo Acute Myeloid Leukemia. AB - In brief, we present a case of acute myeloid leukemia (AML) with 5, 17 and 18 monosomies as stemline clonal abnormality in his cytogenetic analysis. To the best of our knowledge, this is the first report of such a chromosomal abnormality as a clonal aberration in AML with M0 French-American-British (FAB) type. It seems that this monosomal karyotype imposed adverse prognosis on this patient and could be related to the rapid and malignant course of the disease as seen. PMID- 27179173 TI - C-doped mesoporous anatase TiO2 comprising 10nm crystallites. AB - We report a C-doped mesoporous anatase TiO2 with high surface area synthesized using multi-walled carbon nanotube (MWCNT) mat as a "rigid" template and carbon doping source. The characterization by SEM, HRTEM, X-ray diffraction and nitrogen adsorption revealed that TiO2 samples have a porous structure which are figuratively a inverse copy of MWCNT network and pore walls are formed by interconnected TiO2 nanoparticles with average diameter of ~10nm. We found that annealing temperatures from 400 to 1000 degrees C before MWCNT template removal had very limited effect on particle size (~10nm), surface area (112-129m(2)/g) and total pore volume (0.74-0.85m(2)/g) of the samples through a significantly delayed phase transition from anatase to rutile started at 800 degrees C, resulting in only ~9.1% conversion at 1000 degrees C. The pore size distribution is in mesopore range from 6 to 60nm peaked at ~24nm. XPS analysis showed a relatively strong C1s peak at 288.4eV, indicating C doping at Ti sites, which is responsible for red shift of adsorption edge of UV-vis spectra and photocatalytic activity in visible-light region. PMID- 27179174 TI - Efficiency enhancement of dye-sensitized solar cells by use of ZrO2-doped TiO2 nanofibers photoanode. AB - Due to the good stability and convenient optical properties, TiO2 nanostructures still the prominent photoanode materials in the Dye Sensitized Solar Cells (DSCs). However, the well-known low bandgap energy and weak adsorption affinity for the dye distinctly constrain the wide application. This work discusses the impact of Zr-doping and nanofibrous morphology on the performance and physicochemical properties of TiO2. Zr-doped TiO2 nanofibers (NFs), with various zirconia content (0, 0.5, 1, 1.5 and 2wt%) were prepared by calcination of electrospun mats composed of polyvinyl acetate, titanium isopropoxyl and zirconium n-propoxyl. For all formulations, the results have shown that the prepared materials are continuous, randomly oriented, and good morphology nanofibers. The average diameter decreased from 353.85nm to 210.78nm after calcination without a considerable influence on the nanofibrous structure regardless the zirconia content. XRD result shows that there is no Rutile nor Brookite phases in the obtained material and the average crystallite size of the sample is affected by the presence of Zr-doping and changed from 23.01nm to 37.63nm for TiO2 and Zr-doped TiO2, respectively. Optical studies have shown Zr doped TiO2 NFs have more absorbance in the visible region than that of pristine TiO2 NFs; the maximum absorbance is corresponding to the NFs having 1wt% zirconia. The improved spectra of Zr-doped TiO2 in the visible region is attributed to the heterostructure composition resulting from Zr-doping. The absorption bandgaps were calculated using Tauc model as 3.202 and 3.217 for pristine and Zr (1wt%)-doped TiO2 NFs, respectively. Furthermore, in Dye sensitized Solar Cells, utilizing Zr (1wt%)-doped TiO2 nanofibers achieved higher efficiency of 4.51% compared to the 1.61% obtained from the pristine TiO2 NFs. PMID- 27179175 TI - Stray-field NMR diffusion q-space diffraction imaging of monodisperse coarsening foams. AB - The technique of stray field diffusion NMR is adapted to study the diffusion properties of water in monodisperse wet foams. We show for the first time, that the technique is capable of observing q-space diffusion diffraction peaks in monodisperse aqueous foams with initial bubble sizes in the range of 50-85MUm. The position of the peak maximum can be correlated simply to the bubble size in the foam leading to a technique that can investigate the stability of the foam over time. The diffusion technique, together with supplementary spin-spin relaxation analysis of the diffusion data is used to follow the stability and coarsening behaviour of monodisperse foams with a water fraction range between 0.24 and 0.33. The monodisperse foams remain stable for a period of hours in terms of the initial bubble size. The duration of this stable period correlates to the initial size of the bubbles. Eventually the bubbles begin to coarsen and this is observed in changes in the position of the diffusion diffraction maxima. PMID- 27179176 TI - Bimodal fibrous structures for tissue engineering: Fabrication, characterization and in vitro biocompatibility. AB - We report for the first time a polycaprolactone-human serum albumin (PCL-HSA) membrane with bimodal structures comprised of spider-web-like nano-nets and conventional fibers via facile electro-spinning/netting (ESN) technique. Such unique controllable morphology was developed by electrospinning the blend solution of PCL (8wt% in HFIP 1,1,1,3,3,3,-Hexafluoro-2-propanol) and HSA (10wt% deionized water). The phase separation during electrospinning caused the formation of bimodal structure. Various processing factors such as applied voltage, feeding rate, and distance between nozzle tip and collector were found responsible for the formation and distribution of the nano-nets throughout the nanofibrous mesh. Field emission electron microscopy (FE-SEM) confirmed that the nano-nets were composed of interlinked nanowires with an ultrathin diameter (10 30nm). When compared with a pure PCL membrane, the membrane containing nano-nets was shown to have better support for cellular activities as determined by cell viability and attachment assays. These results revealed that the blending of albumin, a hydrophilic biomolecule, with PCL, a hydrophobic polymer, proves to be an outstanding approach to developing membranes with controlled spider-web-like nano-nets for tissue engineering. PMID- 27179177 TI - Designing the inner surface corrugations of hollow fibers to enhance CO2 absorption efficiency. AB - For the first time, a low cost strategy is introduced to enhance the efficiency of CO2 absorption using gas-liquid membrane contactors. This is implemented by designing the corrugations in the inner layer of poly(vinyl chloride) hollow fibers (PVC HFs) through changing the bore fluid composition. In fact, the number of corrugations in the HF inner layer is engineered via changing the phase separation time within the inner layer. Such that expedited phase separation leads to highly corrugated inner layer. In contrast, decelerated phase separation is responsible for reduced number of inner layer corrugations. Phase separation causes the initial polymer solution with low viscoelastic moduli to be transferred into polymer-rich domains with high viscoelastic moduli. These domains resist against stretching-induced radial forces toward the center of HF; therefore, the inner layer of HF buckles. Delayed phase separation defers formation of polymer-rich domains and hence, HF with less corrugated inner surface is expected. The phase separation within the HF inner layer is controlled through changing the rate of solvent/nonsolvent exchange. This is conducted by variation the solvent content in the bore fluid; as higher as solvent content, as slower as solvent/nonsolvent exchange. PMID- 27179178 TI - Synthesis and biological evaluation of novel pyrazolopyrimidines derivatives as anticancer and anti-5-lipoxygenase agents. AB - A novel series of 6-aryl-3-methyl-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-ones 3a-h were synthesized in a single step via condensation of carboxamide 2 with some aromatic aldehydes (presence of iodine). Treatment of aminopyrazole 1a with acetic anhydride afforded pyrazolopyrimidines 4 which on treatment with ethyl chloroacetate in refluxing dry DMF furnished a single product identified as ethyl 2-(3,6-dimethyl-4-oxo-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-5(4H)-yl) acetate 5. On the other hand, esterification of compound 6 with different alcohol, led to the formation of new esters linked pyrazolo[3,4-d]pyrimidinones hybrids 7a-f. The reaction of compound 2 with 3-propargyl bromide gave the compound 8 used as a dipolarophile to access to triazoles (4- and 5-regioisomers (9a-e) and (10a-e), respectively) via the 1,3-dipoar cycloaddition reaction. Finally, condensation reaction of aminopyrazole 1b with alpha-cyanocinnamonitiles gave the new pyrazolo[1,5-a]pyrimidine-3,6-dicarbonitriles 11a-e. Structures of compounds were established on the basis of (1)H/(13)C NMR and ESI-HRMS. Compounds were screened for their cytotoxic (HCT-116 and MCF-7) and 5-lipoxygenase inhibition activities. The structure-activity relationship (SAR) was discussed. PMID- 27179179 TI - Inflammation biomarkers and mortality prediction in patients with type 2 diabetes (ZODIAC-27). AB - BACKGROUND: C-reactive protein (CRP), procalcitonin (PCT) and pro-adrenomedullin (MR-proADM) are inflammation markers associated with long-term mortality risk. We compared the associations and predictive capacities of CRP, PCT and MR-proADM with cardiovascular and all-cause mortality in patients with type 2 diabetes. METHODS: This study included primary care treated patients with type 2 diabetes participating in the ZODIAC cohort study. A total of 1005 out of 1688 patients (60%) had complete baseline variables. Baseline CRP, PCT and MR-proADM were assessed in relation to cardiovascular and all-cause mortality with Cox proportional hazard analyses. Hazard Ratios (HR) were adjusted for age, gender, BMI, smoking, systolic blood pressure, cholesterol-HDL ratio, duration of diabetes, HbA1c, history of cardiovascular diseases, albumin-creatinine ratio and creatinine. Risk prediction capabilities were assessed with Harrell's C statistics and proportion of explained variance (R(2)). RESULTS: After a median follow-up of 11 years, 472 (47%) of 1005 patients had died. The likelihood ratio test showed that CRP and MR-proADM significantly improved prediction in cardiovascular mortality [HRs 1.20 (95%CI 1.09-1.33) and 1.56 (95%CI 1.06-2.30)] and in all-cause mortality [HRs 1.10 (95%CI: 1.03-1.18) and 1.31 (95%CI 1.02 1.69)]. Harrell's C values and R(2) measures showed slightly improved discrimination for cardiovascular mortality in patients without macrovascular disease (C: 0.80 to 0.81; R(2): 0.50 to 0.52) and MR-proADM (C: 0.80 to 0.82; R(2): 0.50 to 0.52). CONCLUSIONS: CRP and MR-proADM, but not PCT, were independently associated with cardiovascular and all-cause mortality. In patients without macrovascular diseases, CRP and MR-proADM slightly improved discrimination, in absolute sense, of patients at risk for cardiovascular mortality. PMID- 27179180 TI - Physical restraint for psychiatric patients and its associations with clinical characteristics and the National Mental Health Law in China. AB - Physical restraint (PR) for patients is an ongoing controversial topic in psychiatry. This study examined the percentage of PR and its associations with clinical characteristics and the implementation of the National Mental Health Law (NMHL) in China. The study consecutively assessed a sample of 1364 psychiatric inpatients. Socio-demographic and clinical data including use of PR were collected from the medical records using a form designed for this study and confirmed via interview. Psychopathology and insight were measured using standardized instruments. The percentage of PR was 27.2% in the whole sample with 30.7% and 22.4% occurring respectively before and after the NMHL implementation (p=0.001). In multiple logistic regression analysis PR was positively associated with unemployment, lower income, aggression in the past month, being admitted before the NMHL implementation and poorer insight. The percentage of PR in Chinese psychiatric patients is associated with various clinical factors and appeared to decrease after the implementation of the NMHL. Focused and individualized care for patients who are unemployed, have low income, recent aggression and poor insight would be necessary at early stages of admission. PMID- 27179181 TI - Depression and anxiety among patients with somatoform disorders, panic disorder, and other depressive/anxiety disorders in Taiwan. AB - The aim of this study is to compare the severity of depression and anxiety in individuals with somatoform disorders, panic disorder, other depressive/anxiety disorders, and healthy controls in a Han Chinese population. According to the DSM IV-TR-based diagnostic interviews, we recruited 152 subjects with somatoform disorders (SG), 56 with panic disorder (PG), 85 with other depressive/anxiety disorders (OG), and 179 without any psychiatric disorder (NG). The four groups reported on the Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI) for depressive and anxiety symptoms, respectively. Correlation analysis and multivariate regression analysis were used to determine the effects of demographic factors and psychiatric diagnoses on depressive and anxiety symptoms separately. BDI-II scores were not significantly different in SG, PG, and OG but were higher than NG. SG and PG had the highest BAI scores, whereas NG had the lowest. Multiple linear regression analyses revealed that the associated factors for BDI-II were gender, residential location, somatoform disorders, panic disorder, major depressive disorder (MDD), and generalized anxiety disorder, whereas BAI was significantly associated with somatoform disorders, panic disorder, and MDD. Our results strongly suggest the inclusion of clinical assessment of depressive and anxious symptoms in patients with somatoform disorders. PMID- 27179182 TI - Relationships between high-density lipoprotein cholesterol and depressive symptoms: Findings of the Korean National Health and Nutrition Examination Survey (KNHANES). AB - Although serum cholesterol has been associated with late-life depression, few studies on the associations between lipids and depression among middle-aged adults have been performed. This study examined associations between serum lipid levels and depressive symptoms in Korean middle-aged adults. We used data from 8207 participants aged 40-64 years who completed a questionnaire about their experience of depressive symptoms over the last year as part of the 2010-2012 Korean National Health and Nutrition Examination Survey. Higher HDL-C levels were significantly associated with an elevated risk of depressive symptoms (OR=1.32; 95% CI=1.09-1.60) after adjusting for other covariates. PMID- 27179183 TI - Coping with suicidal urges among youth seen in a psychiatric emergency department. AB - This study of youth seeking psychiatric emergency department (ED) services examined (1) youth self-efficacy to use suicide-specific coping strategies, (2) whether these self-efficacy beliefs varied by demographic and clinical characteristics, (3) and associations of these beliefs with suicide attempts and ED visits 3-5 months later. Participants were 286 psychiatric ED patients (59% Female), ages 13-25. Ratings of self-efficacy to engage in 10 suicide-specific coping behaviors were assessed at index visit. A total of 226 participants (79%) were assessed 3-5 months later. Youth endorsed low-to-moderate self-efficacy for different suicide-specific coping behaviors, with lowest ratings endorsed for limiting access to lethal means and accessing professional resources. More severe baseline psychopathology was associated with lower self-efficacy. Males endorsed higher self-efficacy for coping behaviors not requiring external support. Lower coping self-efficacy for some of the key strategies, and lower confidence that these strategies will be helpful, differentiated those with and without follow-up suicide attempts and ED visits. The generally low-to-moderate confidence in youths' ability to engage in coping behaviors to manage suicidal crises, and its association with follow-up suicidal crises, is concerning because many of these strategies are commonly included as part of discharge recommendations or safety planning. Implications of findings are discussed. PMID- 27179184 TI - A strengths-based case management service for people with serious mental illness in Israel: A randomized controlled trial. AB - Case management services for people with serious mental illness are generally found to be effective, but controlled and randomized studies assessing such services are scarce. The aim of the present study was to assess the effectiveness of a new strengths-based case management (SBCM) service in Israel, using a randomized controlled approach. The sample consisted of 1276 individuals with serious mental illness, who consume psychiatric rehabilitation services (PRS) in the community, and were randomly assigned to receive or not to receive the SBCM service in addition to treatment-as-usual PRS. Quality of life, goal setting and attainment, unmet needs, self-efficacy, interpersonal relationships, symptom severity, and service utilization were assessed by clients at onset and after 20 months. Results show that SBCM participants improved in self-efficacy, unmet needs, and general quality of life, and set more goals than the control group. SBCM participants also consumed fewer services at follow-up. Results suggest that SBCM services are effective in helping individuals with serious mental illness set personal goals and use PRS in a better and more focused manner. PMID- 27179185 TI - Development and validation of a rapid and sensitive UPLC-MS/MS method for determination of uracil and dihydrouracil in human plasma. AB - Quantification of the endogenous dihydropyrimidine dehydrogenase (DPD) substrate uracil (U) and the reaction product dihydrouracil (UH2) in plasma might be suitable for identification of patients at risk of fluoropyrimidine-induced toxicity as a result of DPD deficiency. In this paper, we describe the development and validation of a rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay for quantification of U and UH2 in human plasma. Analytes were extracted by protein precipitation, chromatographically separated on an Acquity UPLC((r)) HSS T3 column with gradient elution and analyzed with a tandem mass spectrometer equipped with an electrospray ionization source. U was quantified in the negative ion mode and UH2 in the positive ion mode. Stable isotopes for U and UH2 were used as internal standards. Total chromatographic run time was 5min. Validated concentration ranges for U and UH2 were from 1 to 100ng/mL and 10 to 1000ng/mL, respectively. Inter-assay bias and inter-assay precision for U were within +/-2.8% and <=12.4%. For UH2, inter-assay bias and inter-assay precision were within +/-2.9% and <=7.2%. Adequate stability of U and UH2 in dry extract, final extract, stock solution and plasma was demonstrated. Stability of U and UH2 in whole blood was only satisfactory when stored up to 4hours at 2-8 degrees C, but not at ambient temperatures. An accurate, precise and sensitive UPLC-MS/MS assay for quantification of U and UH2 in plasma was developed. This assay is now applied to support clinical studies with fluoropyrimidine drugs. PMID- 27179186 TI - Comparative assessment of bioanalytical method validation guidelines for pharmaceutical industry. AB - The concepts, importance, and application of bioanalytical method validation have been discussed for a long time and validation of bioanalytical methods is widely accepted as pivotal before they are taken into routine use. United States Food and Drug Administration (USFDA) guidelines issued in 2001 have been referred for every guideline released ever since; may it be European Medical Agency (EMA) Europe, National Health Surveillance Agency (ANVISA) Brazil, Ministry of Health and Labour Welfare (MHLW) Japan or any other guideline in reference to bioanalytical method validation. After 12 years, USFDA released its new draft guideline for comments in 2013, which covers the latest parameters or topics encountered in bioanalytical method validation and approached towards the harmonization of bioanalytical method validation across the globe. Even though the regulatory agencies have general agreement, significant variations exist in acceptance criteria and methodology. The present review highlights the variations, similarities and comparison between bioanalytical method validation guidelines issued by major regulatory authorities worldwide. Additionally, other evaluation parameters such as matrix effect, incurred sample reanalysis including other stability aspects have been discussed to provide an ease of access for designing a bioanalytical method and its validation complying with the majority of drug authority guidelines. PMID- 27179187 TI - Quantitative analysis of tivantinib in rat plasma using ultra performance liquid chromatography with tandem mass spectrometry. AB - In this work, a simple, sensitive and fast ultra performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the quantitative determination of tivantinib in rat plasma. Plasma samples were processed with a protein precipitation. The separation was achieved by an Acquity UPLC BEH C18 (2.1mm*50mm, 1.7MUm) column with a gradient mobile phase consisting of 0.1% formic acid in water and acetonitrile. Detection was carried out using positive-ion electrospray tandem mass spectrometry via multiple reaction monitoring (MRM). The validated method had an excellent linearity in the range of 1.0-100ng/mL (r(2)>0.9967) with a lower limit of quantification (1.0ng/mL). The extraction recovery was in the range of 79.4-84.2% for tivantinib and 80.3% for carbamazepine (internal standard, IS). The intra- and inter-day precision was below 8.9% and accuracy was from -7.2% to 9.5%. No notable matrix effect and astaticism was observed for tivantinib. The method has been successfully applied to a pharmacokinetic study of tivantinib in rats for the first time, which provides the basis for the further development and application of tivantinib. PMID- 27179188 TI - Liquid chromatography-tandem mass spectrometric assay for ponatinib and N desmethyl ponatinib in mouse plasma. AB - Ponatinib is a multi-targeted third generation BCR-ABL1 tyrosine-kinase inhibitor approved for specific types of leukemia. A bioanalytical assay for this drug and its N-desmethyl metabolite in mouse plasma was developed and validated using liquid chromatography-tandem mass spectrometric (LC-MS/MS) with liquid-liquid extraction as sample pre-treatment procedure. After extraction with tert-butyl methyl ether of both analytes with their isotopically labeled internal standards and evaporation and reconstitution of the extract, compounds were separated by reversed-phase liquid chromatography under alkaline conditions. After electrospray ionization, both compounds were quantified in the selected reaction monitoring mode of a triple quadrupole mass spectrometer. The linear assay was validated in the ranges 5-5000ng/ml for ponatinib and 1-1000ng/ml for N-desmethyl ponatinib. Within-run (n=18) and between-run (3 runs; n=18) precisions were 10% and 12% at the lower limit of quantification for the metabolite, all other precisions were <=8% for the metabolite and <=6% for ponatinib. Accuracies were between 92 and 108% for both compounds in the whole calibration range. The drug was sufficiently stable under most relevant analytical conditions, only ponatinib showed more than 15% hydrolytic degradation after storage for 6h and longer at ambient temperature in mouse plasma. Finally, the assay was successfully applied to determine plasma drug levels and study pharmacokinetics after oral administration of ponatinib to female FVB mice. PMID- 27179189 TI - Determination of dexmedetomidine in children's plasma by ultra-performance liquid chromatography tandem mass spectrometry and application to pharmacokinetic study. AB - A rapid, sensitive, and selective ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed and validated for the determination and pharmacokinetic investigation of dexmedetomidine in children's plasma. Sample preparation was accomplished through a simple one-step deproteinization procedure with 0.2mL of acetonitrile to a 0.1mL plasma sample. Plasma samples were separated by UPLC on an Acquity UPLC BEH C18 column using a mobile phase consisting of acetonitrile-0.1% formic acid in water with gradient elution. The total run time was 3.1min and the elution of dexmedetomidine was at 1.24min. The detection was performed on a triple quadrupole tandem mass spectrometer in the multiple reaction-monitoring mode using the respective transitions m/z 201.3 >95.1 for dexmedetomidine and m/z 204.2->98.0 for the internal standard, respectively. The calibration curve was linear over the range of 0.05-10ng/mL with a lower limit of quantitation of 0.05ng/mL. Mean recovery rate of dexmedetomidine in plasma was in the range of 86.7-89.1%. Intra-day and inter-day precision were both <11.6%. This method was successfully applied in pharmacokinetic study after commencement of 1.0MUg/kg dexmedetomidine infusion in children. PMID- 27179190 TI - A robust LC-MS/MS method for the determination of pidotimod in different biological matrixes and its application to in vivo and in vitro pharmacokinetic studies. AB - Pidotimod, (R)-3-[(S)-(5-oxo-2-pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid, was frequently used to treat children with recurrent respiratory infections. Preclinical pharmacokinetics of pidotimod was still rarely reported to date. Herein, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to determine pidotimod in rat plasma, tissue homogenate and Caco-2 cells. In this process, phenacetin was chosen as the internal standard due to its similarity in chromatographic and mass spectrographic characteristics with pidotimod. The plasma calibration curves were established within the concentration range of 0.01-10.00MUg/mL, and similar linear curves were built using tissue homogenate and Caco-2 cells. The calibration curves for all biological samples showed good linearity (r>0.99) over the concentration ranges tested. The intra- and inter-day precision (RSD, %) values were below 15% and accuracy (RE, %) was ranged from -15% to 15% at all quality control levels. For plasma, tissue homogenate and Caco-2 cells, no obvious matrix effect was found, and the average recoveries were all above 75%. Thus, the method demonstrated excellent accuracy, precision and robustness for high throughput applications, and was then successfully applied to the studies of absorption in rat plasma, distribution in rat tissues and intracellular uptake characteristics in Caco-2 cells for pidotimod. PMID- 27179191 TI - Attention and executive functions in the early course of pediatric epilepsy. AB - OBJECTIVE: Our prospective study aimed at exploring attention and executive functions in children with new-onset epilepsy prior to and during the early course of antiepileptic treatment. Sociodemographic and epilepsy-related factors were analyzed as potential predictors both of impaired cognitive functions as well as for changes in cognitive functioning in the early course of illness. METHODS: From a total group of 115 children aged six to 17years without major disabilities, 76 children were assessed longitudinally with a screening tool for attention and executive functions (EpiTrack Junior(r)). Sociodemographic variables (gender, age at epilepsy onset, need of special education) and epilepsy related variables (etiology of epilepsy, semiology of seizures, number of seizures) were considered as potential predictors for impaired functions prior to treatment and for deterioration/amelioration in cognitive functions in the early course. RESULTS: Attention and executive functions of children with new-onset epilepsy were significantly more often impaired when compared with a healthy population, but less often when compared with children with chronic epilepsy. The majority of children showed stable cognitive functioning in the early course of treatment. The risk of impaired cognitive functions was significantly heightened when etiology of epilepsy was unknown or not classifiable. The chance for improvement of functioning was lowered by having a genetic epilepsy, or an unknown semiology of seizures. CONCLUSIONS: Children with new-onset epilepsy are at high risk for impaired attention and executive functions even prior to antiepileptic treatment, especially when etiology of their epilepsy remains unclear. The high stability of cognitive functioning in the early course can be used in counseling of families who worry about negative side effects of drug treatment. Finally, a systematic assessment of cognitive functions in children with new-onset epilepsy is necessary to detect subtle deficits in the early course and adjust treatment accordingly. PMID- 27179192 TI - Social cognition in temporal lobe epilepsy: A systematic review and meta analysis. AB - Objective: There is increasing evidence suggesting that social cognitive abilities are impaired in temporal lobe epilepsy (TLE), the most common form of focal epilepsies. Methods: In this meta-analysis, 31 studies investigating theory of mind (ToM) and facial emotion recognition performances of 1356 patients with TLE (351 postsurgery) and 859 healthy controls were included. Results: Patients with TLE had significant deficits in ToM (d = 0.73-0.89) and recognition of facial emotions. There were no significant differences in severity of social cognitive deficits between patients with TLE with or without medial temporal lobectomy. Earlier onset of seizures was associated with ToM impairment. Right sided TLE was associated with more severe deficits in recognition of fear, sadness, and disgust. Conclusions: Social cognitive information processing is impaired in TLE, and the potential role of these deficits in functional impairment needs to be further investigated. PMID- 27179193 TI - Psychoses in epilepsy: A comparison of postictal and interictal psychoses. AB - We retrospectively analyzed data of patients with epilepsy (n=1434) evaluated with prolonged EEG monitoring in order to estimate the prevalence of postictal psychosis (PP) and interictal psychosis (IP), to investigate a potential association of psychosis subtype with epilepsy type, and to assess differences between PP and IP. The overall prevalence of psychosis was 5.9% (N=85); prevalence of PP (N=53) and IP (N=32) was 3.7% and 2.2%, respectively. Of patients with psychosis, 97.6% had localization-related epilepsy (LRE). Prevalence of psychosis was highest (9.3%) in patients with temporal lobe epilepsy (TLE). When comparing PP with IP groups on demographic, clinical, and psychopathological variables, patients with IP were younger at occurrence of first psychosis (P=0.048), had a shorter interval between epilepsy onset and first psychosis (P=0.002), and more frequently exhibited schizophreniform traits (conceptual disorganization: P=0.008; negative symptoms: P=0.017) than those with PP. Postictal psychosis was significantly associated with a temporal seizure onset on ictal EEG (P=0.000) and a higher incidence of violent behavior during psychosis (P=0.047). To conclude, our results support the presumption of a preponderance of LRE in patients with psychosis and that of a specific association of TLE with psychosis, in particular with PP. Given the significant differences between groups, PP and IP may represent distinct clinical entities potentially with a different neurobiological background. PMID- 27179194 TI - White matter disruption is associated with persistent seizures in tuberous sclerosis complex. AB - BACKGROUND AND AIMS: White matter is diffusely altered in tuberous sclerosis complex (TSC), and these alterations appear to be more evident in subjects with a more severe neurologic phenotype. However, little is known on the correlation between white matter alterations and epilepsy in TSC. The aims of this study were to evaluate the effects of early onset and refractory seizures on white matter by using diffusion tensor imaging (DTI). METHODS: We enrolled 20 children with TSC and epilepsy onset in the first 3years of life and grouped them according to seizure persistence or freedom. All patients underwent brain MRI with DTI. Specific ROIs have were placed to generate tracks to calculate fractional anisotropy (FA) and apparent diffusion coefficient (ADC). Statistical analysis was performed by ANOVA. RESULTS: Children with persistent seizures presented an overall reduced FA, with statistically significant differences on the cingulum (right p=0.003, left p=0.016), the left cerebral peduncle (p=0.020), the superior cerebellar peduncles (right p=0.008, left p=0.002), the posterior limbs of internal capsule (right p=0.037, left p=0.015), the external capsule (right p=0.018, left p=0.031), the inferior frontooccipital fasciculus (right p=0.010, left p=0.026), and the temporal trunk (right p=0.017, left p=0.001). CONCLUSIONS: Our study demonstrated that children with persistent seizures present more significant alterations of brain connectivity in areas crucial for global cognitive maturation, executive functions, and verbal abilities, implying a higher risk of cognitive impairment, attention-deficit hyperactivity disorder, and autism. PMID- 27179195 TI - Complementary and alternative medicines use among pediatric patients with epilepsy in a multiethnic community. AB - OBJECTIVE: Prior studies highlighted that patients on chronic medications who used complementary and alternative medicines (CAMs) did not share this information with their healthcare providers. Furthermore, there might be potential adverse interactions between CAMs and antiepileptic drug (AED) therapy. However, there are no studies that investigate the effect of religion or race on CAM use in a multiethnic community. Therefore, we aimed to investigate CAM usage among pediatric patients with epilepsy (PPE) and identify predictors of CAM usage in our multiethnic setting. METHODS: This was a cross-sectional study where caregivers of recruited at an outpatient epilepsy clinic between September 2013 and July 2014 completed a self-administered survey. Those who declined participation, lacked understanding of English or Mandarin, or missed the clinic appointments were excluded. Those caring for more than one patient participated only once. RESULTS: Of the 195 surveys collected, 178 were used for analysis. The PPE used an average of 1.50 AEDs (range: 0-4). Forty-nine (27.5%) caregivers reported giving CAMs to their PPE. Commonly used CAMs were multivitamins (44.4%), traditional herbs (42.2%), and acupuncture (17.4%). Multivitamins were mostly given by Christian/Catholic caregivers while Buddhist caregivers mostly gave traditional herbs or acupuncture. The majority of the CAM users were Chinese. Univariate analysis showed that caregivers with secondary school (high school) education were 3.52 times more likely to use CAMs compared to those with primary school (elementary school) education. CONCLUSIONS: While some caregivers gave CAMs to their PPE, they had various misconceptions and did not discuss the usage with their healthcare providers. We propose that the predictors identified in this study can help to identify potential CAM users. Healthcare providers should routinely probe about the usage of CAMs by PPE, and thereafter, the suitability of CAM use could be evaluated. The caregivers will benefit from open discussion with healthcare professionals on the safe use of AEDs with or without CAMs. PMID- 27179196 TI - Electrochemical study of quinone redox cycling: A novel application of DNA-based biosensors for monitoring biochemical reactions. AB - This paper presents the results of an experimental investigation of voltammetric and impedimetric DNA-based biosensors for monitoring biological and chemical redox cycling reactions involving free radical intermediates. The concept is based on associating the amounts of radicals generated with the electrochemical signals produced, using differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS). For this purpose, a pencil graphite electrode (PGE) modified with multiwall carbon nanotubes and poly-diallydimethlammonium chloride decorated with double stranded fish sperm DNA was prepared to detect DNA damage induced by the radicals generated from a redox cycling quinone (i.e., menadione (MD; 2-methyl-1,4-naphthoquinone)). Menadione was employed as a model compound to study the redox cycling of quinones. A direct relationship was found between free radical production and DNA damage. The relationship between MD-induced DNA damage and free radical generation was investigated in an attempt to identify the possible mechanism(s) involved in the action of MD. Results showed that DPV and EIS were appropriate, simple and inexpensive techniques for the quantitative and qualitative comparisons of different reducing reagents. These techniques may be recommended for monitoring DNA damages and investigating the mechanisms involved in the production of redox cycling compounds. PMID- 27179197 TI - How to sell a condom? The impact of demand creation tools on male and female condom sales in resource limited settings. AB - Despite condoms being cheap and effective in preventing HIV, there remains an 8billion shortfall in condom use in risky sex-acts. Social marketing organisations apply private sector marketing approaches to sell public health products. This paper investigates the impact of marketing tools, including promotion and pricing, on demand for male and female condoms in 52 countries between 1997 and 2009. A static model differentiates drivers of demand between products, while a dynamic panel data estimator estimates their short- and long run impacts. Products are not equally affected: female condoms are not affected by advertising, but highly affected by interpersonal communication and HIV prevalence. Price and promotion have significant short- and long-run effects, with female condoms far more sensitive to price than male condoms. The design of optimal distribution strategies for new and existing HIV prevention technologies must consider both product and target population characteristics. PMID- 27179198 TI - An elicitation of utility for quality of life under prospect theory. AB - This paper performs several tests of decision analysis applied to the health domain. First, we conduct a test of the normative expected utility theory. Second, we investigate the possibility to elicit the more general prospect theory. We observe risk aversion for gains and losses and violations of expected utility. These results imply that mechanisms governing decisions in the health domain are similar to those in the monetary domain. However, we also report one important deviation: utility is universally concave for the health outcomes used in this study, in contrast to the commonly found S-shaped utility for monetary outcomes, with concave utility for gains and convex utility for losses. PMID- 27179200 TI - Improving the cyanide toxicity tolerance of anaerobic reactor: Microbial interactions and toxin reduction. AB - Anaerobic biological treatment of high organics containing wastewater is amongst the preferred treatment options but poor tolerance to toxins makes its use prohibitive. In this study, efforts have been made to understand the key parameters for developing anaerobic reactor, resilient to cyanide toxicity. A laboratory scale anaerobic batch reactor was set up to treat cyanide containing wastewater. The reactor was inoculated with anaerobic sludge obtained from a wastewater treatment plant and fresh cow dung in the ratio of 3:1. The focus was on acclimatization and development of cyanide-degrading biomass and to understand the toxic effects of cyanide on the dynamic equilibrium between various microbial groups. The sludge exposed to cyanide was found to have higher bacterial diversity than the control. It was observed that certain hydrogenotrophic methanogens and bacterial groups were able to grow and produce methane in the presence of cyanide. Also, it was found that hydrogen utilizing methanogens were more cyanide tolerant than acetate utilizing methanogens. So, effluents from various industries like electroplating, coke oven plant, petroleum refining, explosive manufacturing, and pesticides industries which are having high concentrations of cyanide can be treated by favoring the growth of the tolerant microbes in the reactors. It will provide much better treatment efficiency by overcoming the inhibitory effects of cyanide to certain extent. PMID- 27179199 TI - Village sanitation and child health: Effects and external validity in a randomized field experiment in rural India. AB - Over a billion people worldwide defecate in the open, with important consequences for early-life health and human capital accumulation in developing countries. We report a cluster randomized controlled trial of a village sanitation intervention conducted in rural Maharashtra, India designed to identify an effect of village sanitation on average child height, an outcome of increasing importance to economists. We find an effect of approximately 0.3 height-for-age standard deviations, which is consistent with observations and hypotheses in economic and health literatures. We further exploit details of the planning and implementation of the experiment to study treatment heterogeneity and external validity. PMID- 27179201 TI - Variable effects of oxytetracycline on antibiotic resistance gene abundance and the bacterial community during aerobic composting of cow manure. AB - Livestock manure is often subjected to aerobic composting but little is known about the variation in antibiotic resistance genes (ARGs) during the composting process under different concentrations of antibiotics. This study compared the effects of three concentrations of oxytetracycline (OTC; 10, 60, and 200mg/kg) on ARGs and the succession of the bacterial community during composting. Very similar trends were observed in the relative abundances (RAs) of each ARG among the OTC treatments and the control during composting. After composting, the RAs of tetC, tetX, sul1, sul2, and intI1 increased 2-43 times, whereas those of tetQ, tetM, and tetW declined by 44-99%. OTC addition significantly increased the absolute abundances and RAs of tetC and intI1, while 200mg/kg OTC also enhanced those of tetM, tetQ, and drfA7. The bacterial community could be grouped according to the composting time under different treatments. The highest concentration of OTC had a more persistent effect on the bacterial community. In the present study, the succession of the bacterial community appeared to have a greater influence on the variation of ARGs during composting than the presence of antibiotics. Aerobic composting was not effective in reducing most of the ARGs, and thus the compost product should be considered as an important reservoir for ARGs. PMID- 27179202 TI - Removal of trimethoprim, sulfamethoxazole, and triclosan by the green alga Nannochloris sp. AB - Trimethoprim (TMP), sulfamethoxazole (SMX), and triclosan (TCS) are widely used and continuously released into aquatic environments. Freshwater algae can be responsible for the uptake and transfer of the contaminants because they are a major food source for most aquatic organisms. This research applied incubation studies to evaluate the removal efficiency of TMP, SMX, and TCS by the green alga Nannochloris sp. The results showed that the hydrophilic antibiotics TMP and SMX remained in the algal culture at 100% and 68%, respectively, after 14days of incubation, and therefore were not significantly removed from the medium. However, the lipophilic antimicrobial TCS was significantly removed from the medium. Immediately after incubation began, 74% of TCS dissipated and 100% of TCS was removed after 7days of incubation. Additionally, over 42% of TCS was found associated with the algal cells throughout the incubation. The results demonstrate that the presence of Nannochloris sp. eliminated TCS in the aquatic system, but could not significantly remove the antibiotics TMP and SMX. The removal mechanisms of SMX and TCS were found to be different in the algal culture. Algae-promoted photolysis was the primary process for removing SMX and algae-mediated uptake played a major role in removing TCS. PMID- 27179203 TI - Impacts of sanitation upgrading to the decrease of fecal coliforms entering into the environment in China. AB - Identifying the sanitation efficacy of reducing fecal contaminations in the environment is important for evaluating health risks of the public and developing future management strategies to improve sanitation conditions. In this study, we estimated the fecal coliforms (FC) entering into the environment in 31 provinces in China under three sanitation scenarios. Our calculation results indicated that, the current FC release is disparate among regions, and the human releases in the rural regions were dominant, accounting for over 90% of the total human releases. Compared with the human release, the FC release from the livestock was of similar magnitude, but has a quite different spatial distribution. In China Women's Development Program, the Chinese government set the target to make over 85% of the population in the rural access to the toilets in 2020. If the target set by the Chinese government is achieved, a decrease of 34% (12-54%) in the FC releases would be anticipated. In the future, the improvement in sanitation and accesses to the safe drinking water in the less developed regions, such as Tibet, Qinghai, and Ningxia, should be considered as a priority. PMID- 27179204 TI - Occurrence and sources of brominated and organophosphorus flame retardants in dust from different indoor environments in Barcelona, Spain. AB - In this study, the simultaneous presence of eight polybrominated diphenyl ethers (PBDEs), nine new brominated flame retardants (NBFRs) and ten organophosphorus flame retardants (OPFRs) was investigated in dust samples collected from different indoor environments (homes, schools, theatres, a university and a Research Institute) in Barcelona, Spain. OPFRs were detected at the highest concentrations followed by PBDEs. ?OPFRs ranged from 2053 to 72,090ngg(-1) and tris(2-chloroisopropyl) phosphate (TCIPP) was the most abundant compound. BDE-209 was the main PBDE congener detected (up to 14,990ngg(-1)), while other PBDEs ranged from 2.6 to 118ngg(-1). Among the studied NBFRs, decabromodiphenyl ethane (DBDPE - up to 4432ngg(-1)) followed by bis(2-ethylhexyl) tetrabromophthalate (BEH-TEBP - up to 508ngg(-1)) were detected at the highest concentration, whereas a lower detection frequency was observed for 2-ethylhexyl 2,3,4,5 tetrabromobenzoate (EH-TBB), 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), pentabromotoluene (PBT) and hexabromobenzene (HBB). The levels and profile of flame retardants (FRs) were characteristic of each environment, where theatres followed by homes presented the highest concentrations and schools had the lowest levels. Principal Component Analysis permitted to identify the main sources and distribution of all FRs, according to specific uses in each environment. The simultaneous presence of all FR families in indoor dust points to the need to monitor these compounds to minimize human exposure. PMID- 27179205 TI - Longitudinal strain of systemic right ventricle correlates with exercise capacity in adult with transposition of the great arteries after atrial switch. AB - BACKGROUND: Systemic right ventricle (sRV) dysfunction in d-transposition of the great arteries following atrial switch (d-TGA) is associated with increased mortality. We aimed to characterize maladaptive sRV mechanisms in d-TGA patients, analyzing relation of echocardiographic parameters of sRV systolic function to objective measurements of exercise capacity. METHODS: Forty-seven adult patients with d-TGA and atrial switch (mean age 31.6+/-4.2years) underwent conventional echocardiography, bidimensional strain (2D-strain), cardiac magnetic resonance (CMR) imaging and cardiopulmonary exercise evaluation on the same day. Those with median peak oxygen uptake (VO2)>64.5% (n=23) constituted group A, those with VO2<=64.5% (n=24) constituted group B and 23 healthy age and gender matched subjects constituted the control group. RESULTS: In group A, global longitudinal peak systolic 2D-strain (GLS) of sRV was significantly reduced compared to GLS of normal RV and LV in the healthy control group (p<0.01), however peak longitudinal 2D strain was similar at basal and mid-segment of sRV free wall than normal LV. In group B, GLS was significantly reduced compared to group A (-10.9+/-2.9% vs 13.1+/-2.3%, p<0.05), mostly due to significant decrease of interventricular septum longitudinal strain. Other echocardiographic systolic parameters were not significantly different between groups A and B. Only sRV GLS showed significant correlation with functional capacity as measured by VO2 (r=0.42, p<0.01), while CMR RVEF did not. CONCLUSION: GLS of sRV predicts functional capacity and may be more sensitive than CMR RVEF in detecting early myocardial damage of sRV in patients with d-TGA and atrial switch. PMID- 27179206 TI - Circulating endothelial microparticles are elevated in bicuspid aortic valve disease and related to aortic dilation. AB - BACKGROUND/OBJECTIVES: The mechanisms underlying aortic dilation in bicuspid aortic valve (BAV) disease are unknown. Circulating endothelial microparticles (EMPs) have emerged as biomarkers of endothelial damage. We sought to evaluate the relationships among EMPs, BAV disease, and aortic dilation. METHODS: Four evaluations were used. Circulating EMPs (PECAM(+), E-selectin(+)) were compared between BAV patients and tricuspid aortic valve (TAV) control subjects. The variables related to circulating EMPs were investigated in BAV patients. Circulating EMP levels were compared between BAV and TAV patients with a dilated aorta. Finally, circulating EMPs in BAV patients were evaluated over time with respect to aortic valve surgery (AVS) or aortic surgery. RESULTS: We observed higher levels of circulating PECAM(+) EMPs in the BAV patients than in the control subjects (3.98+/-0.2 vs. 2.39+/-0.4 per log PECAM(+) EMPs/MUl, p=0.001). Aortic dilation was the most significant variable that correlated with the PECAM(+) EMP levels in the BAV patients (beta=0.321, p=0.008). The BAV patients with aortic dilation exhibited higher PECAM(+)EMP levels than the TAV patients with dilated aortas, and this correlation was independent of aortic valve function. We observed a drastic decrease in the circulating PECAM(+) EMPs following AVS and aortic root replacement (4.27+/-0.6 and 1.75+/-0.3 per log PECAM(+)EMPs/MUl, p=0.002). CONCLUSION: The observed pattern of higher circulating PECAM(+) EMP levels links BAV disease to endothelial damage and aortic dilation. Circulating PECAM(+) EMPs were identified as a biological variable related to aortic dilation in patients with BAV disease. PMID- 27179207 TI - The HAS-BLED score predicts long-term major bleeding and death in anticoagulated non-valvular atrial fibrillation patients undergoing electrical cardioversion. AB - BACKGROUND: Atrial fibrillation (AF) patients eligible for cardioversion tend to be younger and are at lower risk than 'general' AF clinic populations. We evaluated the incidence of major bleeding and death, as well as the predictive value of the HAS-BLED score in non-valvular AF patients who underwent electrical cardioversion (ECV). METHODS: Consecutive non-valvular AF patients who underwent ECV were recruited. Major bleeding episodes and mortality were recorded. Factors associated with both endpoints and the predictive value of the HAS-BLED score were analysed. RESULTS: 406 patients (281 males; age 66.9+/-10.9years) undergoing 571 ECV were included. After a follow-up of nearly 3years, 20 patients presented with major bleeding (1.9%/year;) and 26 patients died (2.4%/year). The HAS-BLED score predicted both major bleeding [c-statistics: 0.77; 95%CI: 0.71-0.83; p<0.001] and mortality [c-statistics: 0.83; 95%CI: 0.79-0.87; p<0.001]. Variables associated with bleeding were: renal impairment (HR: 4.35; 95%CI: 1.22-15.52; p=0.02), poor quality anticoagulation (HR: 3.21; 95%CI: 1.11-9.32; p=0.03), previous bleeding-predisposition (HR: 5.43; 95%CI: 1.76-16.75; p=0.003) and the HAS-BLED score (HR: 1.88; 95%CI: 1.34-2.64; p<0.001). Factors associated with mortality were: age (HR: 1.08; 95%CI: 1.03-1.14; p=0.004), poor quality anticoagulation (HR: 3.11; 95%CI: 1.15-8.36; p=0.02), previous bleeding predisposition (HR: 5.90; 95%CI: 1.41-24.65; p=0.01), liver impairment (HR: 9.27; 95%CI:1.64-52.34; p=0.01), the CHA2DS2-VASc score (HR: 1.63; 95%CI: 1.18-2.26; p=0.003) and the HAS-BLED score (HR: 2.74; 95%CI: 1.86-4.04); p<0.001). CONCLUSIONS: In AF patients undergoing ECV, major bleeding episodes and mortality were independently associated with poor quality anticoagulation control and previous bleeding-predisposition. The HAS-BLED score successfully predicted major bleeding and mortality. PMID- 27179208 TI - Obesity and postoperative atrial fibrillation in patients undergoing cardiac surgery: Systematic review and meta-analysis. AB - INTRODUCTION: Post-operative atrial fibrillation (POAF) is one of the most common complications following cardiac surgery. However, it is unclear whether there is a relationship between obesity and POAF. We thus assessed all available evidence investigating the association between obesity and POAF, also considering any link between POAF and other post-operative conditions such as mortality, stroke, myocardial infarctions and respiratory complications. METHODS: Five electronic databases were searched and relevant studies were identified. Data was extracted and meta-analyzed from the identified studies. RESULTS: We found that obese patients had significantly higher odds of POAF when compared with non-obese patients (P=0.006). There was also significant heterogeneity among the identified studies. POAF when compared with no-POAF was associated with an increased risk of stroke (P<0.0001), 30-day mortality (P=0.005) and respiratory complications (P<0.00001). However, we found no significant link between POAF and myocardial infarctions (P=0.79). CONCLUSIONS: Our findings suggest that obesity is associated with a moderately higher risk of POAF. While POAF is also associated with an increased incidence of stroke, 30-day mortality and respiratory complications, further studies must be conducted before conclusions can be made about the long-term outcomes. PMID- 27179209 TI - Impact of preparatory coronary protection in patients at high anatomical risk of acute coronary obstruction during transcatheter aortic valve implantation. AB - BACKGROUND: This study aimed to assess the effectiveness of preparatory coronary protection (CP) in patients considered at high risk of acute coronary obstruction (ACO) after transcatheter aortic valve implantation (TAVI). METHODS: The Optimized CathEter vAlvular iNtervention (OCEAN-TAVI) Japanese multicenter registry enrolled 666 consecutive patients. All patients were assessed by preprocedural multidetector computed tomography. CP using a guide wire with or without a balloon was prospectively performed according to the following criteria: 1) coronary height length from the annulus <10mm, 2) evidence of ACO during balloon aortic valvuloplasty with simultaneous aortic injection, and 3) shallow valsalva or bulky calcification on the leaflet. The incidence of ACO and other procedural outcomes were compared between the CP and non-CP groups. RESULTS: CP was performed in 14.1% of all patients (94/666). ACO had an incidence of 1.5% (10/666) and mainly occurred in women (70%) and the left coronary artery (70%). The ACO rate was significantly higher in the CP group than in the non-CP group (7.4% [7/94] vs. 0.5% [3/572]; p<0.001), although notably 30% of ACO were occurred in non-CP group. All 10 ACO cases were successfully treated by catheter intervention, although periprocedural myocardial injury occurred in 42.9% of patients with CP group and 33.3% of those without CP group. Mortality and other periprocedural complications did not significantly differ between the 2 groups. CONCLUSION: The preparatory CP strategy was feasible for the management of ACO during TAVI, but the complication of ACO was difficult to predict completely. PMID- 27179210 TI - Coronary heart disease mortality, cardiovascular disease mortality and all-cause mortality attributable to dietary intake over 20years in Brazil. AB - BACKGROUND/OBJECTIVES: In the last two decades, in Brazil, there has been a decreasing trend of consumption of in natura or minimally processed food, while intake of ultra-processed food has markedly increased. We estimated the contribution of dietary intake in trends from coronary heart disease mortality (CHDM), cardiovascular disease mortality (CVDM), and all-cause mortality (ACM) over 20years in Brazil. METHODS: We used a representative sample of Brazilian households located in metropolitan areas to estimate dietary intake in 1987/88 and 2008/09. For both periods, we estimated fractions of CHDM, CVDM, and ACM attributable to healthy (fruits and vegetables) and unhealthy food items (sugar sweetened beverages, processed and red meat). We also estimated the number of prevented or postponed deaths attributable to these food items. RESULTS: The fraction of CHDM attributable to all food items increased from 28.6% in 1987/88 to 38.7% in 2008/09. CVDM attributable to food items increased from 13.7% in 1974 to 19.3% in 2008/09. ACM attributable to all food items increased from 20.1% in 1987/88 to 27.3% in 2008/09. Without the decrease in healthy food item consumption, and the increase in unhealthy food items, 3195 deaths from coronary heart disease, 5340 from cardiovascular disease, and 16,970 from all causes could have been prevented or postponed. CONCLUSIONS: The burden of cardiovascular diseases and mortality attributable to dietary intake has increased over the last 20years in Brazil. These findings suggest a need for a population prevention approach, focused on dietary intake to reduce the burden of disease. PMID- 27179211 TI - Long-term administration of ranolazine attenuates diastolic dysfunction and adverse myocardial remodeling in a model of heart failure with preserved ejection fraction. AB - BACKGROUND: To investigate the effects of chronic administration of ranolazine (RAN) on experimental model of heart failure with preserved ejection fraction. METHODS: Seven-weeks old Dahl salt-sensitive rats were fed a high salt diet for 5weeks to induce hypertension. Afterwards, rats continued with a high salt diet and were administered either with vehicle or RAN (20mg/kg/die, ip) for the following 8weeks. Control rats were maintained on a low salt diet. RESULTS: While systolic parameters were not altered, diastolic parameters were changed in high salt animals. Hemodynamic analysis showed a decreased dP/dt min, increased LVEDP, longer time constant and steeper slope of the end-diastolic pressure-volume relationship. Treatment with RAN attenuated these alterations and determined a reduction in mortality. Additionally, the magnitude of myocardial hypertrophy and activation of PI3K/Akt pathway were reduced. Alteration in diastolic compliance as a consequence of elevated myocardial stiffness was confirmed by an increase of collagen deposition and activation of pro-fibrotic TGF-beta/SMAD3/CTGF signaling. These effects were counteracted by RAN. High salt rats had a decrease in SERCA2 and an increase in Na(+)/Ca(2+) exchanger (NCX). Treatment with RAN reduced NCX expression and determined an increment of SERCA2. Moreover, the levels of nitrotyrosine and oxidized dyhydroethidium were higher in high salt rats. RAN induced a decrement of oxidative stress, supporting the concept that reduction in ROS may mediate beneficial effects. CONCLUSIONS: Our findings support the possibility that diastolic dysfunction can be attenuated by RAN, indicating its ability to affect active relaxation and passive diastolic compliance. PMID- 27179212 TI - Excessive exercise habits of runners as new signs of hypertension and arrhythmia. AB - BACKGROUND: Excessive exercise may induce arrhythmia, and this risk is higher in middle-aged people. The study aim was to compare the exercise characteristics of middle-aged runners participating in excessive endurance exercise. METHODS: The subjects of this study were 552 runners (mean age; 49.0+/-7.4years) without structural heart disease who performed exercise at least twice per week, had consistently exercised for at least three years, and had finished at least five marathons. The arrhythmia runner group (ARG, n=14) and normal runner group (NRG, n=538) were compared with regard to hemodynamic response, cardiorespiratory fitness level, training history, number of finished races, finishing times, and exercise habits. RESULTS: The mean resting systolic (134.0+/-15.8mmHg) and diastolic (85.8+/-10.9mmHg) blood pressure values indicated pre-hypertension, while the mean maximal SBP (213.7+/-27.4mmHg) values indicated exercise-induced hypertension. The VO2max was significantly higher and the maximal DBP was significantly lower in the ARG than in the NRG (p<0.05). Training history was significantly longer in the ARG than in the NRG (p<0.05), while the number of finished marathons, the finishing times in marathons and the exercise frequency per week didn't differ significantly between the two groups. Exercise intensity was significantly higher in the ARG than in the NRG (p<0.01). CONCLUSIONS: Middle aged long-distance runners showed pre-hypertension and exercise-induced hypertension, and the ARG had higher VO2max values, greater exercise intensities, and longer training histories than the NRG. PMID- 27179213 TI - Predictive ability of HAS-BLED, HEMORR2HAGES, and ATRIA bleeding risk scores in patients with atrial fibrillation. A French nationwide cross-sectional study. AB - OBJECTIVE: The HAS-BLED, ATRIA, and HEMORR2HAGES risk scores were created to evaluate individual bleeding risk in atrial fibrillation (AF). We sought to estimate and compare the predictive ability of these scores for major hemorrhage in AF, including elderly (>=80years) and non-elderly (<80years) patients. METHODS: This cross-sectional study is based on the French National Hospital Database (PMSI), which covers the entire French population. Data from all patients with an AF diagnosis in 2012 were extracted. Demographic and comorbidity data were used to calculate the three bleeding risk scores for each patient. Patients hospitalized with a principal diagnosis of major bleeding were identified. RESULTS: Of the 533,044 AF patients identified, 53.2% were >=80years; 7013 patients (1.3%) were hospitalized for a bleeding event (1785 for intracranial hemorrhage). Bleeding occurred more frequently in patients with higher HAS-BLED, HEMORR2HAGES, and ATRIA scores. In patients >=80years, the c statistics did not differ (p=0.27) between HAS-BLED (0.54; 95% confidence interval [CI]: 0.53-0.54), HEMORR2HAGES (0.53; 95% CI: 0.53-0.54), and ATRIA (0.53; 95% CI: 0.52-0.54). In patients <80years, HAS-BLED (0.59; 95% CI: 0.58 0.60) had a slightly higher c-statistic than HEMORR2HAGES (0.56; 95% CI: 0.55 0.57) and ATRIA (0.55, 95% CI: 0.55-0.56) (p<0.0001). CONCLUSIONS: Given its simplicity and similar performance, HAS-BLED may be an attractive alternative to HEMORR2HAGES for estimation of bleeding risk in AF patients <80years. However, accurate determination of bleeding risk among the elderly is difficult with existing risk-prediction scores, indicating a clear need for improvement in their clinical utility. PMID- 27179214 TI - Gender specific profiles of white coat and masked hypertension impacts on arterial structure and function in the SardiNIA study. PMID- 27179216 TI - Emery-Dreifuss muscular dystrophy: the most recognizable laminopathy. AB - Emery-Dreifuss muscular dystrophy (EDMD), a rare inherited disease, is characterized clinically by humero-peroneal muscle atrophy and weakness, multijoint contractures, spine rigidity and cardiac insufficiency with conduction defects. There are at least six types of EDMD known so far, of which five have been associated with mutations in genes encoding nuclear proteins. The majority of the EDMD cases described so far are of the emerinopathy (EDMD1) kind, with a recessive X-linked mode of inheritance, or else laminopathy (EDMD2), with an autosomal dominant mode of inheritance. In the work described here, the authors have sought to describe the history by which EDMD came to be distinguished as a separate entity, as well as the clinical and genetic characteristics of the disease, the pathophysiology of lamin-related muscular diseases and, finally, therapeutic issues, prevention and ethical aspects. PMID- 27179215 TI - Symmetrical bis-tertiary amines as novel CXCR4 inhibitors. AB - CXCR4 inhibitors are promising agents for the treatment of cancer metastasis and inflammation. A series of novel tertiary amine derivatives targeting CXCR4 were designed, synthesized, and evaluated. The central benzene ring linker and side chains were modified and optimized to study the structure-activity relationship. Seven compounds displayed much more potent activity than the reference drug, AMD3100, in both the binding affinity assay and the blocking of Matrigel invasion functional assay. These compounds exhibited effective concentration ranging from 1 to 100 nM in the binding affinity assay and inhibited invasion from 65.3% to 100% compared to AMD3100 at 100 nM. Compound IIn showed a 50% suppressive effect against carrageenan-induced paw inflammation in a mouse model, which was as effective as the peptidic antagonist, TN14003 (48%). These data demonstrate that symmetrical bis-tertiary amines are unique CXCR4 inhibitors with high potency. PMID- 27179217 TI - Histopathological comparison of Kearns-Sayre syndrome and PGC-1alpha-deficient mice suggests a novel concept for vacuole formation in mitochondrial encephalopathy. AB - Despite the current hypotheses about myelinic and astrocytic ion-dyshomeostasis underlying white (WM) and grey matter (GM) vacuolation in mitochondrial encephalopathies, there is a paucity of data on the exact mechanism of vacuole formation. To revisit the concepts of vacuole formation associated with mitochondrial dysfunction, we performed a comparative neuropathological analysis in Kearns-Sayre syndrome (KSS) and full-length peroxisome proliferator-activated receptor-g coactivator-1a (FL-PGC-1a)-deficient mice, a recently proposed morphological model of mitochondrial encephalopathies. Brain tissues from an individual with genetically proven KSS (22-year-old man) and aged FL-PGC-1a deficient and wild-type (male, 70-75-week-old) mice were analysed using ultrastructural and immunohistochemical methods, with a specific focus on myelin related, oligodendroglial, axonal and astrocytic pathologies. Besides demonstrating remarkable similarities in the lesion profile of KSS and FL-PGC-1a deficient mice, this study first provides morphological evidence for the identical origin of WM and GM vacuolation as well as for the presence of intracytoplasmic oligodendroglial vacuoles in mitochondriopathies. Based on these observations, the paper proposes a theoretical model for the development of focal myelin vacuolation as opposed to the original concepts of intramyelin oedema. Placing oligodendrocytes in the centre of tissue lesioning in conditions related to defects in mitochondria, our observations support the rationale for cytoprotective targeting of oligodendrocytes in mitochondrial encephalopathies, and may also have implications in brain aging and multiple sclerosis, as discussed. PMID- 27179218 TI - Identification of a novel inherited ALK variant M1199L in the WNT type of medulloblastoma. AB - Rearrangements involving the ALK gene were identified in a variety of cancers, including paediatric tumour neuroblastoma where presence of ALK expression is also associated with adverse prognosis. Microarrays data indicate that ALK is expressed in another paediatric tumour - medulloblastoma. Therefore, we investigated if the ALK gene is mutated in medulloblastoma and performed simultaneously the molecular profiling of tumours. Tumours from sixty-four medulloblastoma patients were studied for detection of ALK alterations in exons 23 and 25 using Sanger method. The molecular subtypes of tumours were identified by detection of mutations in the CTNNB1 gene, monosomy 6 and by immunohistochemistry using a panel of representative antibodies. Among three ALK variants detected two resulted in intron variants (rs3738867, rs113866835) and the third one was a novel heterozygous variant c.3595A>T in exon 23 identified in the WNT type of tumour. It resulted in methionine to leucine substitution at codon position 1199 (M1199L) of the kinase domain of ALK protein. Results of analysis using three in silico algorithms confirmed the pathogenicity of this single nucleotide variation. The same gene alteration was detected in both patient and maternal peripheral blood leukocytes indicating an inherited type of the detected variant. Presence of ALK expression in tumour tissue was confirmed by immunohistochemistry. The tumour was diagnosed as classic medulloblastoma, however with visible areas of focal anaplastic features. The patient has been disease free for 6 years since diagnosis. This is the first evidence of an inherited ALK variant in the WNT type of medulloblastoma, what altogether with presence of ALK expression may point towards involvement of the ALK gene in this type of tumours. PMID- 27179220 TI - Angiocentric glioma from a perspective of A-B-C classification of epilepsy associated tumors. AB - Angiocentric glioma (AG) is a newly-classified, very rare, WHO grade I central nervous system (CNS) lesion, occurring usually in children and young adults. Only 52 patients with AG have been reported so far, making it one of the rarest neuropathological entities. Hereby we present two new cases of AG in young subjects with detailed neuropathological investigations and a neuroradiological picture along with a brief summary of all already published literature reports of this tumor. Histopathological examination of the resected tissue from both cases revealed similar changes characteristic of AG. The tumors were composed of spindle-like, elongated cells, forming characteristic pseudorosettes around vessels and diffusively infiltrating surrounding tissue, trapping neurons between tumor cells. Noticeably, some neoplastic cells encrusting vessels extended far beyond the main tumor mass. Hypothetically, this may be responsible for the recurrence of the tumor even in the case of apparently total excision. In immunohistochemistry, AG cells were glial fibrillary acidic protein (GFAP) and vimentin positive, also exhibiting a strikingly significant epithelial membrane antigen (EMA) dot-like staining pattern. In one of the cases, electron microscopy revealed ependymal differentiation features such as microvilli and cilia. Taken together, all these data strongly confirm a dual astroglial-ependymal nature of the tumor. Follow up corroborates benign character of this neoplasm. Both AGs reported here were immunonegative for the product of the mutated IDH-1 gene what, according to our best knowledge, has never been reported so far. It may suggest that in their pathogenesis AGs differ from grade II astrocytomas, which in most cases harbor a mutation of IDH-1. Noteworthy, neuroimaging in our cases was relatively characteristic but not conclusive, therefore biopsy (at least) is mandatory. A newly proposed so called "A-B-C" classification of long-term epilepsy-associated tumors (LEATs) places AG in a category named ANET. The authors shortly review the A-B-C classification of LEATs. PMID- 27179219 TI - Analysis of Olig2 and YKL-40 expression: a clinicopathological/immunohistochemical study for the distinction between subventricular zone II and III glioblastomas. AB - Glioblastomas (GBs) are the most common and lethal primary brain tumors in the adults. Glioblastomas originates either from astrocytes that have accumulated mutations and de-differentiated or from neural stem cells within the subventricular zone (SVZ) in close contact with the vasculature. Recently, several studies have hypothesized that gliomagenesis occurs in perivascular niches with highly invasive peripheral proliferating zones. The purpose of our study was to investigate the pathological and clinical significance of Olig2 and YKL40 immunoexpression in 152 GBs in relationship to the SVZ II and III. Olig2 expressions were successfully detected in 12 (15.58%) of 77 SVZ type II GBs and 16 (21.3%) of 75 SVZ type III GBs, respectively. YKL-40 expression was observed in 45 (58.4%) of 77 SVZ type II GBs and in 17 (22.6%) of 75 SVZ type III GBs, respectively. Stepwise multivariate Cox proportional hazards models were used, and the prognostic factors to significantly impact OS were: PFS < 54 weeks (HR: 5.86; CI: 3.02-11.33; p = 0.00); radiotherapy (HR: 0.34; CI: 0.18-0.60; p = 0.00); radio- and chemotherapy (HR: 0.05; CI: 0.03-0.10; p = 0.0), and YKL-40+ GBs (HR: 1.61; CI: 1.28-2.31; p = 0.01). PMID- 27179221 TI - Time-related morphometric studies of neurofilaments in brain contusions. AB - In forensic pathology age determination of injuries is of key importance. The purpose of the study was to analyze morphometrically changes in neurofilaments following the brain contusion and relate them to the length of the time of survival. To do this, the authors analyzed specimens of brains collected during medicolegal autopsies. According to the available literature, no such study involving material from deceased humans was conducted. The researched material was divided into nine subgroups (10 cases each) according to the time of death of persons: immediately at the crime site, 12 hours, 24 hours, 2 days, 3 days, 4 days, 5 days, 6 days and 7 days after head trauma. Neurofilaments were immunohistochemically stained and evaluated quantitatively using the Met-Ilo computer application. The initial results were then analyzed statistically with the one way analysis of variance (ANOVA) and the least significant difference (LSD) tests. It was calculated that there are significant differences in numbers and area fractions of neurofilaments within 7 days after head trauma. It must be concluded that morphometric analysis of neurofilaments is a promising method but further studies are required. PMID- 27179222 TI - Pelizaeus-Merzbacher disease in patients with molecularly confirmed diagnosis. AB - Pelizaeus-Merzbacher disease (PMD) is X-linked hypomyelinating leukodystrophy caused by mutations of the PLP1 gene, which codes the proteolipid protein 1. The result of mutations is abnormal myelination - hypomyelination and dysmyelination of cerebral white matter, and in some form of the disease hypomyelinating peripheral neuropathy. DNA samples from 68 patients suspected of PMD due to the clinical course and hypomyelination at magnetic resonance imaging (MRI) were analyzed. Medical history and detailed clinical course of PMD patients were also analyzed. Different mutations of the PLP1 gene were detected in 14 boys from 11 families (~20%). Amongst the molecularly confirmed patients, 13 presented classical PMD forms but clinical phenotypes varied in the severity even amongst siblings. One patient presented a severe connatal form. One mother, obligate carrier, presented complicated SPG2 (spastic paraparesis). There was no phenotype genotype correlation in our material. In many cases PMD was suspected with a delay of many years, sometimes only after birth of another affected child in the family. Pelizaeus-Merzbacher disease was most frequently misdiagnosed as cerebral palsy. PMID- 27179223 TI - Application of molecular imaging combined with genetic screening in diagnosing MELAS, diabetes and recurrent pancreatitis. AB - AIM: We report molecular imaging combined with gene diagnosis in a family with 7 members who carried an A3243G mutation in mitochondrial tRNA and p.Thr 137 Met in cationic trypsinogen (PRSS1) gene presented with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), diabetes, and recurrent pancreatitis. MATERIAL AND METHODS: DNA sequencing was used to detect and validate mitochondrial DNA and PRSS1. We also verified that mitochondrial heterozygous mutations and c.410 C>T mutation causing p.Thr 137 Met could be detected in oral epithelial cells or in urine sediment cells. In addition, molecular imaging was carried out in the affected family members. RESULTS: In this pedigree, MELAS syndrome accompanied by pancreatitis was an important clinical feature, followed by diabetes. Heteroplasmy of the mtDNA A3243G and c.410 C>T mutation of PRSS1 was found in all tissue samples of these patients, but no mutations were found in 520 normal control and normal individuals of the family. However, based on molecular imaging observations, patients with relatively higher lactate/pyruvate levels had more typical and more severe symptoms, particularly those of pancreatic disease (diabetes or pancreatitis). CONCLUSIONS: MELAS syndrome may be associated with pancreatitis. For the diagnosis, it is more reasonable to perform molecular imaging combined with gene diagnosis. PMID- 27179224 TI - Late dissemination via cerebrospinal fluid of papillary tumor of the pineal region: a case report and literature review. AB - Papillary tumor of the pineal region (PTPR) represents a recently described entity and was included in the 2007 World Health Organization (WHO) classification of central nervous system tumors. The biological and clinical behavior of PTPR is variable and may correspond to WHO grades II or III. Papillary tumor of the pineal region can show aggressive biological behavior with local relapses and dissemination via the cerebrospinal fluid. Several cases of PTPR with leptomeningeal seeding and multiple lesions or spinal metastasis have been reported. We present an unusual clinical history of papillary tumor of the pineal region with ventricular and spinal dissemination five years after primary surgical treatment. PMID- 27179225 TI - Rosette-forming glioneuronal tumour of the fourth ventricle: case report and review of the literature. AB - Rosette-forming glioneuronal tumour (RGNT) of the fourth ventricle is one of the newly described primary tumours of the central nervous system. These tumours have two components of both neurocytic and glial areas but usually the glial component of the tumour predominates. They have biphasic cytoarchitecture with two elements; neurocytic rosettes resembling Homer-Wright rosettes, and astrocytic component resembling a pilocytic astrocytoma. They are low-grade tumours with lack of histopathological signs of malignancy. Here, clinical, magnetic resonance, computed tomography (CT) and pathological features of rosette-forming glioneuronal tumour of posterior fossa are presented. A 29-year-man was admitted with an acute neurological deterioration. A three ventricular hydrocephalus and a hypo-density around vermis in the posterior fossa were seen in his CT scans. He did well after an emergency external ventricular drainage. He had an elective operation and a mass that was reported to be a rosette-forming glioneuronal tumour of the fourth ventricle was excised. PMID- 27179226 TI - Clinical strategies for the management of intestinal obstruction and pseudo obstruction. A Delphi Consensus study of SICUT (Societa Italiana di Chirurgia d'Urgenza e del Trauma). AB - BACKGROUND: Intestinal obstructions/pseudo-obstruction of the small/large bowel are frequent conditions but their management could be challenging. Moreover, a general agreement in this field is currently lacking, thus SICUT Society designed a consensus study aimed to define their optimal workout. METHODS: The Delphi methodology was used to reach consensus among 47 Italian surgical experts in two study rounds. Consensus was defined as an agreement of 75.0% or greater. Four main topic areas included nosology, diagnosis, management and treatment. RESULTS: A bowel obstruction was defined as an obstacle to the progression of intestinal contents and fluids generally beginning with a sudden onset. The panel identified four major criteria of diagnosis including absence of flatus, presence of >3.5 cm ileal levels or >6 cm colon dilatation and abdominal distension. Panel also recommended a surgical admission, a multidisciplinary approach, and a gastrografin swallow for patients presenting occlusions. Criteria for immediate surgery included: presence of strangulated hernia, a >10 cm cecal dilatation, signs of vascular pedicles obstructions and persistence of metabolic acidosis. Moreover, rules for non-operative management (to be conducted for maximum 72 hours) included a naso-gastric drainage placement and clinical and laboratory controls each 12 hours. Non-operative treatment should be suspended if any suspects of intra-abdominal complications, high level of lactates, leukocytosis (>18.000/mm3 or Neutrophils >85%) or a doubling of creatinine level comparing admission. Conversely, consensus was not reached regarding the exact timing of CT scan and the appropriateness of colonic stenting. CONCLUSIONS: This consensus is in line with current international strategies and guidelines, and it could be a useful tool in the safe basic daily management of these common and peculiar diseases. KEY WORDS: Delphi study, Intestinal obstruction, Large bowel obstruction, Pseudo-obstruction, Small bowel. PMID- 27179227 TI - Jugular diameter and venous reflux. AB - OBJECTIVES: Aims of this study were to investigate the prevalence of reflux on internal jugular veins(IJV) by Valsalva maneuver and to define the association between reflux of IJV in subjects with both CCSVI and MS. METHODS: We recruited 393 patients with MS and CCSVI. Study participants underwent EchoColor Doppler exam in order to define IJV diameter at confluence in subclavian (JSd). Subjects were divided in three groups: group "1=10 mm" (subjects with jugular diameter equal or more than 10 mm). RESULTS: In our sample the Jugular mean diameter was 8 +/- 2 mm. There were not significant differences in mean diameter values in left/right jugular, after grouping jugular diameters into three groups by mean sample values +/- standard deviation. Veins >=10mm were more observed than veins <=6 mm. Significant difference were found in male vs female prevalence of subject included in "JSd>=10 mm" (30.7% vs 16.7%. X2 =22.9622 with df=2 p<0.0001). Regarding the group "JSd>=10 mm", while in males the Valsalva+/Valsalva- ratio was about 1:3, in females the ratio was about 1:2. Female are more aged in "JSd>=10 mm" group vs female subjects in "1=10 mm" group (about 1:2 vs. 1:3).r Moreover jugular dilatations are equally present in left and right side and it can confirm the wall Miopragia hypothesis. The prevalence of V+ maneuver grows with the IJV diameter, therefore we presume that IJV dilatation is linked with the presence of jugular reflux. Further studies are required to consolidate our observations. KEY WORDS: CCSVI, Jugular vein diameter, Valsalva maneuver. PMID- 27179228 TI - Do twisted laser beams evoke nuclear hyperpolarization? AB - The hyperpolarization of nuclear spins promises great advances in chemical analysis and medical diagnosis by substantially increasing the sensitivity of nuclear magnetic resonance (NMR). Current methods to produce a hyperpolarized sample, however, are arduous, time-consuming or costly and require elaborate equipment. Recently, a much simpler approach was introduced that holds the potential, if harnessed appropriately, to revolutionize the production of hyperpolarized spins. It was reported that high levels of hyperpolarization in nuclear spins can be created by irradiation with a laser beam carrying orbital angular momentum (twisted light). Aside from these initial reports however, no further experimental verification has been presented. In addition, this effect has so far evaded a critical theoretical examination. In this contribution, we present the first independent attempt to reproduce the effect. We exposed a sample of immersion oil or a fluorocarbon liquid that was placed within a low field NMR spectrometer to Laguerre-Gaussian and Bessel laser beams at a wavelength of 514.5nm and various topological charges. We acquired (1)H and (19)F NMR free induction decay data, either during or alternating with the irradiation that was parallel to B0. We observed an irregular increase in NMR signal in experiments where the sample was exposed to beams with higher values of the topological charge. However, at no time did the effect reach statistical significance of 95%. Given the measured sensitivity of our setup, we estimate that a possible effect did not exceed a hyperpolarization (at 5mT) of 0.14-6%, depending on the assumed hyperpolarized volume. It should be noted though, that there were some differences between our setup and the previous implementation of the experiment, which may have inhibited the full incidence of this effect. To approach a theoretical description of this effect, we considered the interaction of an electron with a plane wave, which is known to be able to induce electronic (e.g. in rubidium) and subsequent nuclear hyperpolarization. Compared to the plane wave, the additional transitions caused by a twisted wave are of the order of 10(-3) less. This suggests that the twist of the laser is unlikely to be responsible for the hyperpolarization of nuclear spins, unless a new mechanism of momentum transfer is identified. PMID- 27179229 TI - LAGB: regular follow-up with an interdisciplinary team is the key to success in terms of weight loss and complications. AB - BACKGROUND: In severe obesity, most patients do not respond to conventional treatment. Bariatric surgery must only be proposed in specific cases. LAGB gives excellent long-term results if patient scrupulously complies the follow-up. STUDY AIM: To evaluate patients who comply with the follow-up procedure over time in terms of weight loss, maintenance of the result, complications and quality of life. METHODS: 209 patients underwent LAGB between October 1999 and December 2007 and followed for 5 years. all patients were offered interdisciplinary counseling to update the therapeutic strategy. RESULTS: Out of 92 patients who after two years had reached the desired weight 58 patients (63%) had a regular follow- up and, when necessary, specific counseling. 34 patients (37%) who did not plan follow-up did not maintain the weight loss, and progressively put on weight between the second and fifth year and had a higher incidence of complications. (SF-36) established in patients regularly followed improvement of the quality of life (QoL), up to the fifth year. Short Form Health Survey patients who did not regularly have follow-up the SF-36 showed a worsening of all the test domains between the second and the fifth year. CONCLUSIONS: After 5 years, patients with severe obesity (BMI> 40) who underwent LAGB, that took part in a interdisciplinary follow-up procedure, obtained a full rehabilitation with a change of lifestyle, and maintained the weight loss obtained after 24 months. The perceived quality of life (QoL) shows a progressive improvement throughout the period of intensive intervention. Long-term efficacy of LAGB depends on a scrupulous followup and interdisciplinary support. KEY WORDS: LAGB, Obesity, Psychotherapy, SF-36. PMID- 27179230 TI - Early cessation and non-response are important and possibly related problems in growth hormone therapy: An OZGROW analysis. AB - OBJECTIVE: To investigate growth hormone (GH) treatment and treatment cessation with respect to efficacy and efficiency. To identify factors that best classify or predict cessation type: completed treatment (CT), early cessation (EC), or non response (NR). DESIGN: Observational study (1990-2013) of the Australian GH Program comparing CT, EC, and NR groups with respect to demographic, clinical, and response criteria. All patients treated for GH deficiency (GHD; 909), short stature and slow growth (SSSG; 2144), and Turner Syndrome (TS; 626) were included. Information was retrieved from the OZGROW database. RESULTS: 51.9% of patients were EC, 40.7% CT and 7.4% NR.Median treatment durations for NR patients were often longer than patients who completed treatment. EC and NR groups were both associated with poor growth response with males overrepresented.Socioeconomic status differentiated NR (higher) and EC (lower) groups. CONCLUSIONS: EC was observed at very high rates and appears, generally, to be a little-recognised but frequent problem in GH therapy.EC and delayed recognition of NR may be interrelated being differentiated by the decision to cease or continue treatment following poor response.Poor treatment compliance is likely a major causal factor in EC.Strategies to address poor response and compliance have been developed, however, given the scale of these problems, it may be that long acting GH formulations or individualized treatment need consideration. PMID- 27179231 TI - Usefulness of ileostomy defunctioning stoma after anterior resection of rectum on prevention of anastomotic leakage A retrospective analysis. AB - PURPOSES: Anastomotic leakage is one of the major complications occurring after anterior resection of rectum. A defunctioning stoma is usually created routinely or on surgeons' discretion. The aim of this study was to investigate the usefulness of temporary ileostomy to prevent anastomotic leakage comparing the postoperative course of patients with and without defunctioning loop ileostomy. METHODS: Patients that underwent anterior resection of rectum were recruited. 140 patients were enrolled and divided in two groups: patients without and with defunctioning loop ileostomy. Patients' characteristics and other useful data were recorded. A comparison between the two groups was made. The minimum follow up was 11 months. RESULTS AND CONCLUSIONS: 18.6% of patients had a symptomatic anastomotic leakage. We observed more anastomotic leakages after medium-low resections of rectum with anastomosis than after resections with high anastomosis (15.7% vs 2.9%; p=0.03). There were no significant differences in overall and related mortality between patients without/with ileostomy. The presence of ileostomy was not protective towards anastomotic leakage either in the medium-low resections or in the high ones but it was towards its consequences such as clinical features. Nevertheless we found a statistically significative difference between recurrence rate of leakage in patients with and without ileostomy (p Value=0.009). KEY WORDS: Anterior resection of rectum, Ileostomy, Leakage. PMID- 27179232 TI - Symptoms of depression and anxiety in youth with type 1 diabetes: A systematic review and meta-analysis. AB - INTRODUCTION: The interaction between psychosocial factors and type 1 diabetes is complex and screening for psychosocial risk factors from diagnosis of type 1 diabetes has been recommended. This is a systematic review and meta-analysis to address the following questions: (1) How prevalent are symptoms of depression and anxiety in children and adolescents with type 1 diabetes? (2) Is there an association of symptoms of depression and anxiety with diabetes management and glycemic control? MATERIAL AND METHODS: We searched EMBASE, MEDLINE, The Cochrane Library, and PsycINFO in April 2014 with an update in May 2015. When possible, data were pooled to estimate summary effects. RESULTS: 14 studies investigated symptoms of depression and anxiety in children and adolescents with type 1 diabetes. The pooled prevalence of depressive symptoms was 30.04%, 95% CI [16.33; 43.74]. There were correlations between symptom levels and glycemic control as well as three-way interactions between HbA1c, blood glucose monitoring frequency or diabetes-specific stress and depression. Symptoms of anxiety were reported for up to 32% of patients. A negative impact on glycemic control was demonstrated. CONCLUSIONS: Our analyses confirmed a high prevalence of symptoms of depression and anxiety in youth with type 1 diabetes that potentially compromise diabetes management and glycemic control. In our opinion these findings support recommendations for early screening for psychological comorbidity and regular psychosocial assessment from diagnosis. Future prospective studies are warranted to further explore the interaction of symptoms of depression and anxiety with type 1 diabetes and develop evidence-based treatment models. PMID- 27179233 TI - Genetic predisposition for high stress reactivity amplifies effects of early-life adversity. AB - A dysregulation of the hypothalamus-pituitary-adrenocortical (HPA) axis and the experience of early-life adversity are both well-established risk factors for the development of affective disorders, such as major depression. However, little is known about the interaction of these two factors in shaping endophenotypes of the disease. Here, we studied the gene-environment interaction of a genetic predisposition for HPA axis dysregulation with early-life stress (ELS), assessing the short-, as well as the long-lasting consequences on emotional behavior, neuroendocrine functions and gene expression profiles. Three mouse lines, selectively bred for either high (HR), intermediate (IR), or low (LR) HPA axis reactivity, were exposed to one week of ELS using the limited nesting and bedding material paradigm. Measurements collected during or shortly after the ELS period showed that, regardless of genetic background, ELS exposure led to impaired weight gain and altered the animals' coping behavior under stressful conditions. However, only HR mice additionally showed significant changes in neuroendocrine stress responsiveness at a young age. Accordingly, adult HR mice also showed lasting consequences of ELS, including hyperactive stress-coping, HPA axis hyperreactivity, and gene expression changes in the Crh system, as well as downregulation of Fkbp5 in relevant brain regions. We suggest that the genetic predisposition for high stress reactivity interacts with ELS exposure by disturbing the suppression of corticosterone release during a critical period of brain development, thus exerting lasting programming effects on the HPA axis, presumably via epigenetic mechanisms. In concert, these changes lead to the emergence of important endophenotypes associated with affective disorders. PMID- 27179234 TI - The Egyptian Red Sea coastal microbiome: A study revealing differential microbial responses to diverse anthropogenic pollutants. AB - The Red Sea is considered one of the youngest oceanic systems, with unique physical, geochemical and biological characteristics. Tourism, industrialization, extensive fishing, oil processing and shipping are extensive sources of pollution in the Red Sea. We analyzed the geochemical characteristics and microbial community of sediments along the Egyptian coast of the Red Sea. Our sites mainly included 1) four ports used for shipping aluminum, ilmenite and phosphate; 2) a site previously reported to have suffered extensive oil spills; and 3) a site impacted by tourism. Two major datasets for the sediment of ten Red Sea coastal sites were generated; i) a chemical dataset included measurements of carbon, hydrogen, nitrogen and sulfur, metals and selected semi-volatile oil; and ii) a 16S rRNA Pyrotags bacterial metagenomic dataset. Based on the taxonomic assignments of the 16S rRNA Pyrotags to major bacterial groups, we report 30 taxa constituting an Egyptian Red Sea Coastal Microbiome. Bacteria that degrade hydrocarbons were predominant in the majority of the sites, particularly in two ports where they reached up to 76% of the total identified genera. In contrast, sulfate-reducing and sulfate-oxidizing bacteria dominated two lakes at the expense of other hydrocarbon metabolizers. Despite the reported "Egyptian Red Sea Coastal Microbiome," sites with similar anthropogenic pollutants showed unique microbial community abundances. This suggests that the abundance of a specific bacterial community is an evolutionary mechanism induced in response to selected anthropogenic pollutants. PMID- 27179235 TI - "Small is beautiful" A series of ileo-anal anastomoses performed with the 25 - mm circular stapler. AB - AIM: With the idea that a small diameter stapler should cause less sphincter trauma, we began to use the 25mm circular stapler to perform ileo-pouch-anal anastomosis (IPAA) and we report our experience. MATERIAL OF STUDY: A retrospective study using a bowel function questionnaire and a quality of life questionnaire has been conducted on a group of patients who underwent IPAA using a 25mm stapler RESULTS: We performed IPAA using a 25mm circular stapler in 37 patients. Postoperative mortality was nil and morbidity was 27%. One anastomotic stenosis occurred. Long term follow-up information was available on 28 patients. Mean follow-up was 70 months (range 8-177). Mean number of bowel movements was 4.5 (range 2-10, median 4.5) during the day and 0.9 (range 0-10, median 0) at night. Out of 28 patients, 19 (68%) were fully continent and 32% had occasional soiling, no one reported incontinence. All patients except one were able to withold their stool for more than 15 minutes. Daytime pad use was: never 86%, occasionally 3%, frequently 11%; nightime pas use was never 86%, occasionally 7% and frequently 7%. Bowel regulating drugs use was never 82%, occasionally 14%, regularly 4%. Evacuation difficulties were: never 75%, occasionally 21%, frequently 4%. DISCUSSION: Our results compare favourably with the literature, which reports median bowel frequency 6-7.6/24h, 9.4- 33% urgency, 17-44% daytime soiling and 32-61% nighttime soiling. CONCLUSIONS: Our results must be considered preliminary but we found the 25-mm stapler safe and adequate to perform IPAA. KEY WORDS: IPAA, Ulcerative Colitis, Stapler, Function. PMID- 27179236 TI - Comparison of multiple training models of surgical rotation for third-year medical students A prospective study. AB - AIM: We decided to compare five different teaching models to provide the best training for third-year medical students during their Surgical Rotation. MATERIALS AND METHODS: Group A got a standard rotation. Group B came to the ward once a week at half morning, spent 1 hour with the tutor and the rest of the morning with residents. Group C was divided into smaller groups, each one assigned 2 times to the ambulatory, to the ward and to the pre-admission service. Group D came to the ward once a week at early morning, spent 2 hours with the tutor and the rest of the morning with residents. Group E was divided in 2 smaller groups that were admitted 3 times in the OR and in the ward. Students filled in an initial and final knowledge-evaluation questionnaire RESULTS: All the Groups showed a positive learning curve. Group B showed the highest improvement (p=0.0001). Group A and Group E showed statistically significant improvements, (p=0.002 and p=0.03). Most of Group A and B students declared that their experience was poor regarding medical examination, while the majority of Group C and E defined their experience satisfactory. CONCLUSIONS: Group B demonstrated the most significant growth and good appreciation from students, but also Group E and Group C showed a high appreciation rate, maybe due to the stimulating activity in the operative room and ambulatory. We propose a synthesis of these models as the best approach, with less crowed groups and ward, ambulatory and OR activities. KEY WORDS: General surgery, Medical students, Surgical education, Surgical clerkship, Students training, Surgical rotation. PMID- 27179237 TI - Polydimethylsiloxane-air partition ratios for semi-volatile organic compounds by GC-based measurement and COSMO-RS estimation: Rapid measurements and accurate modelling. AB - Polydimethylsiloxane (PDMS) shows promise for use as a passive air sampler (PAS) for semi-volatile organic compounds (SVOCs). To use PDMS as a PAS, knowledge of its chemical-specific partitioning behaviour and time to equilibrium is needed. Here we report on the effectiveness of two approaches for estimating the partitioning properties of polydimethylsiloxane (PDMS), values of PDMS-to-air partition ratios or coefficients (KPDMS-Air), and time to equilibrium of a range of SVOCs. Measured values of KPDMS-Air, Exp' at 25 degrees C obtained using the gas chromatography retention method (GC-RT) were compared with estimates from a poly-parameter free energy relationship (pp-FLER) and a COSMO-RS oligomer-based model. Target SVOCs included novel flame retardants (NFRs), polybrominated diphenyl ethers (PBDEs), polycyclic aromatic hydrocarbons (PAHs), organophosphate flame retardants (OPFRs), polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs). Significant positive relationships were found between log KPDMS-Air, Exp' and estimates made using the pp-FLER model (log KPDMS-Air, pp LFER) and the COSMOtherm program (log KPDMS-Air, COSMOtherm). The discrepancy and bias between measured and predicted values were much higher for COSMO-RS than the pp-LFER model, indicating the anticipated better performance of the pp-LFER model than COSMO-RS. Calculations made using measured KPDMS-Air, Exp' values show that a PDMS PAS of 0.1 cm thickness will reach 25% of its equilibrium capacity in ~1 day for alpha-hexachlorocyclohexane (alpha-HCH) to ~ 500 years for tris (4-tert butylphenyl) phosphate (TTBPP), which brackets the volatility range of all compounds tested. The results presented show the utility of GC-RT method for rapid and precise measurements of KPDMS-Air. PMID- 27179239 TI - Soil spreading of liquid olive mill processing wastes impacts leaching of adsorbed terbuthylazine. AB - Olive mill waste water (OMWW) is a major byproduct of the three phase olive oil production process. OMWW has high acidity (pH ~ 4-5), high salt content (EC ~ 5 10 mS cm(-1)), extremely high biological and chemical oxygen demand (BOD and COD up to 100,000 and 220,000 mg L(-1), respectively), and also high concentrations of organic compounds such as phenols and polyphenols. As a result, OMWW cannot be freely discharged into domestic wastewater treatment plants, but on-site treatment is very expensive and not sufficiently effective. Uses for OMWW such as agricultural recycling and co-composting were found to be impractical or expensive. Thus, OMWW is frequently spread on agricultural land for disposal. However, excessive or uncontrolled spreading of such organic-rich and saline wastewater could have many deleterious effects on soil quality, including salinization, phytotoxicity, or contaminant movement. The impact of OMWW on the leaching of adsorbed terbuthylazine, a soil-applied herbicide, was tested in four soils of varying physical and chemical properties. Although terbuthylazine solubility in OMWW is significantly higher than in water, leaching of adsorbed terbuthylazine from OMWW-treated soils was less than from control treatments. Low soil organic carbon and clay contents were major factors that contributed to reduced terbuthylazine leaching after soil treatment with OMWW. PMID- 27179238 TI - Effect of copper on the performance and bacterial communities of activated sludge using Illumina MiSeq platforms. AB - The anaerobic-anoxic-aerobic (A2O) process is a highly efficient sewage treatment method, which uses complex bacterial communities. However, the effect of copper on this process and the bacterial communities involved remains unknown. In this study, a systematic investigation of the effect of persistent exposure of copper in the A2O wastewater treatment system was performed. An A2O device was designed to examine the effect of copper on the removal efficiency and microbial community compositions of activated sludge that was continuously treated with 10, 20, and 40 mg L(-1) copper, respectively. Surprisingly, a decrease in chemical oxygen demand (COD) and ammonia nitrogen (NH4N) removal efficiency was observed, and the toxicity of high copper concentration was significantly greater at 7d than at 1d. Proteobacteria, Bacteroidetes, Acidobacteria, Chlorobi, and Nitrospirae were the dominant bacterial taxa in the A2O system, and significant changes in microbial community were observed during the exposure period. Most of the dominant bacterial groups were easily susceptible to copper toxicity and diversely changed at different copper concentrations. However, not all the bacterial taxa were inhibited by copper treatment. At high copper concentration, many bacterial species were stimulated and their abundance increased. Cluster analysis and principal coordinate analysis (PCoA) based on operational taxonomic units (OTUs) revealed clear differences in the bacterial communities among the samples. These findings indicated that copper severely affected the performance and key microbial populations in the A2O system as well as disturbed the stability of the bacterial communities in the system, thus decreasing the removal efficiency. PMID- 27179240 TI - Bioremediation of lead contaminated soil with Rhodobacter sphaeroides. AB - Bioremediation with microorganisms is a promising technique for heavy metal contaminated soil. Rhodobacter sphaeroides was previously isolated from oil field injection water and used for bioremediation of lead (Pb) contaminated soil in the present study. Based on the investigation of the optimum culturing conditions and the tolerance to Pb, we employed the microorganism for the remediation of Pb contaminated soil simulated at different contamination levels. It was found that the optimum temperature, pH, and inoculum size for R. sphaeroides is 30-35 degrees C, 7, and 2 * 10(8) mL(-1), respectively. Rhodobacter sphaeroides did not remove the Pb from soil but did change its speciation. During the bioremediation process, more available fractions were transformed to less accessible and inert fractions; in particular, the exchangeable phase was dramatically decreased while the residual phase was substantially increased. A wheat seedling growing experiment showed that Pb phytoavailability was reduced in amended soils. Results inferred that the main mechanism by which R. sphaeroides treats Pb contaminated soil is the precipitation formation of inert compounds, including lead sulfate and lead sulfide. Although the Pb bioremediation efficiency on wheat was not very high (14.78% root and 24.01% in leaf), R. sphaeroides remains a promising alternative for Pb remediation in contaminated soil. PMID- 27179241 TI - Inverse modeling of the biodegradation of emerging organic contaminants in the soil-plant system. AB - Understanding the processes involved in the uptake and accumulation of organic contaminants into plants is very important to assess the possible human risk associated with. Biodegradation of emerging contaminants in plants has been observed, but kinetical studies are rare. In this study, we analyse experimental data on the uptake of emerging organic contaminants into lettuce derived in a greenhouse experiment. Measured soil, root and leaf concentrations from four contaminants were selected within the applicability domain of a steady-state two compartment standard plant uptake model: bisphenol A (BPA), carbamazepine (CBZ), triclosan (TCS) and caffeine (CAF). The model overestimated concentrations in most cases, when no degradation rates in plants were entered. Subsequently, biodegradation rates were fitted so that the measured concentrations were met. Obtained degradation kinetics are in the order, BPA < CAF ~ TCS < CBZ in roots, and BPA ~ TCS < CBZ << CAF in leaves. Kinetics determined by inverse modeling are, despite the inherent uncertainty, indicative of the dissipation rates. The advantage of the procedure that is additional knowledge can be gained from existing experimental data. Dissipation kinetics found via inverse modeling is not a conclusive proof for biodegradation and confirmation by experimental studies is needed. PMID- 27179242 TI - Detection and quantification of boscalid and its metabolites in honeybees. AB - Boscalid is a new-generation fungicide that has been detected in several bee matrices. The objective of this work was to characterize boscalid metabolites in honeybees based on in vivo experimentation, and next to verify the presence of theses metabolites into honeybees from colonies presenting troubles. A methodology based on complementary mass spectrometric tools, namely ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-QToF) or triple quadrupole mass spectrometry (UHPLC-QqQ) was implemented. Honeybees were sprayed with boscalid, at field rate (to induce the metabolization process) and the parent compound with its generated metabolites were then extracted using modified EU-QuEChERS method. The mass characteristics including exact mass, isotopic profile and mass fragments allowed assuming the structure of several metabolites. Some of them were unambiguously identified by comparison with synthesized analytical standards. The metabolites were resulted from hydroxylation and dechlorination of the parent compound as well as the substitution of a chlorine atom with an hydroxyl group. The metabolites were then quantified in bee samples collected from various beehives located in France. Boscalid and three of its metabolites were present in some samples at a level ranged between 0.2 and 36.3 ng/g. PMID- 27179243 TI - Removal of arsenic and cadmium with sequential soil washing techniques using Na2EDTA, oxalic and phosphoric acid: Optimization conditions, removal effectiveness and ecological risks. AB - Testing of sequential soil washing in triplicate using typical chelating agent (Na2EDTA), organic acid (oxalic acid) and inorganic weak acid (phosphoric acid) was conducted to remediate soil contaminated by heavy metals close to a mining area. The aim of the testing was to improve removal efficiency and reduce mobility of heavy metals. The sequential extraction procedure and further speciation analysis of heavy metals demonstrated that the primary components of arsenic and cadmium in the soil were residual As (O-As) and exchangeable fraction, which accounted for 60% and 70% of total arsenic and cadmium, respectively. It was determined that soil washing agents and their washing order were critical to removal efficiencies of metal fractions, metal bioavailability and potential mobility due to different levels of dissolution of residual fractions and inter-transformation of metal fractions. The optimal soil washing option for arsenic and cadmium was identified as phosphoric-oxalic acid-Na2EDTA sequence (POE) based on the high removal efficiency (41.9% for arsenic and 89.6% for cadmium) and the minimal harmful effects of the mobility and bioavailability of the remaining heavy metals. PMID- 27179244 TI - Contributions of different biomass components to the sorption of 1,2,4 trichlorobenzene under a series of pyrolytic temperatures. AB - In order to investigate contributions of cellulose (CEL), hemicellulose (HEM), lignin (LIG) to the sorption capacity of biochar derived from lignocellulose, the individual component and their artificially modeled biomass mixture (C-H-L) were pyrolyzed under oxygen-limited condition at various pyrolytic temperatures (i.e. 250, 350, 500, 700 degrees C). The characterization analysis of biochars and sorption batch experiments were carried out. Variations in physiochemical property of different component biochars resulted in discrepancies in their ability to function as sorbents to 1,2,4-trichlorobenzene (1,2,4-TCB). The maximum mass sorption capacity (Qfm) of 1,2,4-TCB was the greatest on CEL biochars ranging from 58.31 to 601.20 mg g(-1), and can be best explained by their huge surface area and micropore volume. Hydrophobic partitioning-sorption into 'soft' amorphous alkyl carbon may account for the second greatest Qfm (45.09 56.57 mg g(-1)) on HEM biochars under low pyrolytic temperatures (250-350 degrees C) with the lowest surface area. LIG biochars with more compact and smooth aromatic structure surface may undergo a surface monolayer specific adsorption. The Qfm (87.86-196.53 mg g(-1)) on C-H-L biochars were largely dependent on CEL and HEM components for their outstanding sorption capacity and higher content in biomass. Therefore, the results highlighted the importance of CEL and HEM components for 1,2,4-TCB sorption to biochar. PMID- 27179245 TI - Effects of experimental long-term CO2 exposure on Daphnia magna (Straus 1820): From physiological effects to ecological consequences. AB - The carbon capture and storage (CCS) technologies that were proposed to mitigate environmental problems arising from anthropogenic CO2 emissions, also have potential environmental risks. An eventual CCS leak might induce very low pH values in the aquatic system. Due to the lack of knowledge of long-term CO2 exposures with very low pH values, this study aims to know the effects and consequences of such a situation for zooplankton, using the Daphnia magna experimental model. A CO2 injection system was used to provide the experimental condition. A twenty-one days experiment with control and low pH treatment (pH = 7) replicates was carried out under light and temperature-controlled conditions. Survival, individual growth, RNA:DNA ratio, and neonates production were analysed during the aforementioned period. No differences on survival (except last day), individual growth and RNA:DNA ratio were observed between both control and low pH treatments. However, clear differences were detected in neonates production and, consequently, in population growth rates and secondary production. The observed differences could be related with an energy allocation strategy to ensure individual survival but would have ecological consequences affecting higher trophic levels. PMID- 27179246 TI - Varicose veins: new trends in treatment in a Vascular Surgery Unit. AB - AIM: Less invasive techniques such as foam sclerotherapy, endovenous laser or radiofrequency ablation have recently been introduced as a valid alternative to surgery for the treatment of varicose veins (VVs). We retrospectively reviewed our experience in the treatment of VVs with particular attention to how our therapeutic approach has changed over the last years. MATERIAL OF STUDY: Data of all patients consecutively treated from September 1st 2013 to July 31st 2015 for both primitive and recurrent VVs were retrospectively collected and analyzed. Statistical analysis was performed using the software JMP 5.1.2 (SAS Institute). RESULTS: A total of 409 legs in 378 patients were treated. The percentage of stripping of the great saphenous veins (GSV) for primary VVs has decreased over the years (67% in 2013 vs 15.2% in 2015), differently from what happened to the percentage of RFA of the GSV (14.3% vs. 31.5% respectively in 2013 and in 2015) and to the percentage of legs treated with the A.S.V.A.L. technique (8.7% vs. 31.5% respectively in 2013 and in 2015). Likewise, in 2013 most procedures were performed using spinal anesthesia (77.5%), while in 2015 the most used anesthetic techniques were both the local anesthesia and the local anesthesia with conscious sedation (35.9% and 29.3% respectively). Postoperative course was uneventful in all cases but seven (1.7%). At follow-up (median 16.9 months, IQR 7.5-22.6 months), neither major adverse events nor deaths were recorded. CONCLUSIONS: During the years of our experience, we observed a trend towards a less invasive approach for the treatment of VVs, with safe and effective results. KEY WORDS: Ablation Radiofrequency, Stripping, Varicose veins. PMID- 27179247 TI - Imaging, biodistribution, and toxicology evaluation of (212)Pb-TCMC-trastuzumab in nonhuman primates. AB - INTRODUCTION: The biodistribution and toxicology of a radiotherapeutic (212)Pb trastuzumab conjugate were evaluated in nonhuman primates to meet the investigational new drug requirements prior to a phase I clinical trial in human subjects. METHODS: Male cynomolgus monkeys (n=3/group) were injected intraperitoneally with the (212)Pb-trastuzumab conjugate and terminated at 8h, 10d, and 90d post-injection. Quantitative imaging studies in phantoms and monkeys were conducted using a planar gamma camera and a high purity germanium (HPGe) detector out to 48h following injection. Biodistribution analyses were conducted at 8h; all tissues and time points were evaluated for macroscopic and microscopic pathology. Blood samples were taken throughout the 90d study period for assessment of hematology parameters and serum chemistry parameters. RESULTS: Quantitative gamma camera imaging and region-of-interest analyses of phantoms and monkeys indicated that 95.5+/-5.0% of the decay-corrected (212)Pb activity was retained in the peritoneal region up to 48h following administration of the (212)Pb-trastuzumab. Gamma-ray spectroscopy analyses confirmed that 87.6+/-4.5% of the decay-corrected (212)Bi activity was also retained in the peritoneal cavity during this time. Serum chemistry parameters for all groups always fell within normal ranges. Gross and histopathology evaluations showed no radiation related toxicity in any tissue at any time. CONCLUSION: In vivo imaging and biodistribution analyses showed that about 90% of both (212)Pb and decay product (212)Bi remained in the monkey peritoneal cavity. The imaging methods could also be applied to human subjects. The lack of toxicity observed in monkeys following intraperitoneal injection of the (212)Pb-trastuzumab conjugate supports its clinical assessment in humans. PMID- 27179248 TI - Cardiovascular side-effects and insulin secretion after intravenous administration of radiolabeled Exendin-4 in pigs. AB - INTRODUCTION: Radiolabeled Exendin-4, a synthetic glucagon-like peptide-1 (GLP-1) analog, is used as a tracer for diagnostic purposes of beta-cells and in experimental animal research. Exendin-4 can be radiolabeled with (68)Ga, (111)In or (99m)Tc and used for positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging to diagnose insulinomas, visualization of pancreatic beta-cell mass and transplanted Islets of Langerhans. In humans, Exendin-4 is widely used as a therapeutic agent for treatment of type 2 diabetes (T2D). The compound, which is administered subcutaneously (SC) may cause nausea, vomiting and a minor increase in the heart rate (HR). However, possible side-effects on cardiovascular functions after intravenous (IV) administration have not been reported. This study describes the Exendin-4 dose at which cardiovascular side-effects occur in pigs and cynomolgus monkeys. The IV effect of the tracer on insulin secretion is also investigated in pigs. METHODS: Seven clinically healthy littermate pigs (40days old) were used; three of them were made diabetic by streptozotocin (STZ). All pigs underwent PET imaging under general anesthesia to examine the glucagon-like peptide-1 receptor (GLP-1R) in beta-cells with radiolabeled Exendin-4. A baseline tracer dose IV [(68)Ga]Exendin 4 (0.025+/-0.010MUg/kg) followed by a competition dose IV [(68)Ga]Exendin-4 (3.98+/-1.33MUg/kg) 60min later were administered. Blood samples were taken and analyzed for insulin secretion by using ELISA. Cardiovascular and respiratory variables were monitored throughout the experiment. RESULTS: Immediately after administration of the high dose [(68)Ga]Exendin-4 the HR rose from 122+/-14 to 227+/-40bpm (p<0.01) and from 100+/-5 to 181+/-13bpm (p<0.01) in healthy non diabetic and diabetes-induced pigs, respectively. The tachycardia was observed for >2h and one healthy non-diabetic pig suffered cardiac arrest 3h after the IV [(68)Ga]Exendin-4. Arrhythmia was detected by listening to the heart with a stethoscope up to 4days after the [(68)Ga]Exendin-4 injection. In all animals, no effect on the cardiovascular system was registered after the low dose of IV [(68)Ga]Exendin-4. Insulin secretion increased (p<0.05) when IV [(68)Ga]Exendin-4 was given in dosages >=0.14MUg/kg. CONCLUSIONS: Intravenous administration of >=2.8MUg/kg [(68)Ga]Exendin-4 resulted in severe tachycardia and arrhythmias in healthy non-diabetic and diabetes-induced pigs, and the insulin secretion was stimulated in healthy non-diabetic animals when >=0.14MUg/kg [(68)Ga]Exendin-4 was given. PMID- 27179249 TI - Preparation and evaluation of the tumor-specific antigen-derived synthetic mucin 1 peptide: A potential candidate for the targeting of breast carcinoma. AB - PURPOSE: The goal of this study was to prepare a synthetic peptide derived from breast tumor associated antigen and to evaluate its potential as a breast cancer imaging agent. METHODS: A mucin 1 derived peptide was synthesized by solid-phase peptide synthesis and examined for its radiochemical and metabolic stability. The tumor cell binding affinity of (99m)Tc-MUC1 peptide was investigated on MUC1 positive T47D and MCF7 breast cancer cell lines. In vivo biodistribution was studied in normal Balb/c mice and in vivo tumor targeting and imaging in MCF7 and T47D tumor-bearing nude mice. RESULTS: The synthesized MUC1-derived peptide displayed high radiochemical and metabolic stability. In vitro tumor cell-binding on T47D and MCF7 cell lines demonstrated high affinity of (99m)Tc-MUC1 peptide towards human breast cancer cells (binding affinities in nanomolar range). Pharmacokinetic studies performed on Balb/c mice are characterized by an efficient clearance from the blood and excretion predominantly through the urinary system. In vivo tumor uptake in nude mice with MCF7 tumor xenografts was 2.77+/-0.63% ID/g as early as 1h p.i. whereas in nude mice with T47D human ductal breast epithelial cancer cells, the accumulation in the tumor was found to be 2.65+/-0.54% ID/g at 1h p.i. Also tumor lesion was detectable in gamma-camera imaging. The tumor uptake values were always higher than the blood and muscle uptake, with good tumor retention and good tumor-to-blood and tumor-to-muscle ratios. A low to moderate (<5% ID/g) accumulation and retention of (99m)Tc-MUC1 was found in the major organs (i.e., lungs, stomach, liver, intestines, kidneys, etc.) in both normal and tumor-bearing mice. CONCLUSION: This study suggests that (99m)Tc-MUC1 tumor-antigen peptide may be a potential candidate for the targeted imaging of MUC1-positive human tumors and warrants further investigation. PMID- 27179250 TI - Biodistribution of (125)I-labeled anti-endoglin antibody using SPECT/CT imaging: Impact of in vivo deiodination on tumor accumulation in mice. AB - INTRODUCTION: Radiolabeled antibodies directed against endoglin (CD105) are promising tools for imaging and antiangiogenic cancer therapy. To validate iodinated antibodies as reliable tracers, we investigated the influence of the radiolabeling method (direct or indirect) on their in vivo stability. METHODS: Anti-CD105 mAbs were radioiodinated directly using chloramine-T ((125)I-anti CD105-mAbs) or indirectly using D-KRYRR peptide as a linker ((125)I-KRYRR-anti CD105-mAbs). The biodistribution was studied in B16 tumor-bearing mice via SPECT/CT imaging. RESULTS: Radioiodinated mAbs were stable in vitro. In vivo, thyroid showed the most important increase of uptake after 24h for (125)I-anti CD105-mAbs (91.9+/-4.0%ID/ml) versus(125)I-KRYRR-anti-CD105-mAbs (4.4+/ 0.6%ID/ml). Tumor uptake of (125)I-anti-CD105-mAbs (0.9+/-0.3%ID/ml) was significantly lower than that of (125)I-KRYRR-anti-CD105-mAbs (4.7+/-0.2%ID/ml). CONCLUSIONS: An accurate characterization of the in vivo stability of radioiodinated mAbs and the choice of an appropriate method for the radioiodination are required, especially for novel targets. The indirect radioiodination of internalizing anti-CD105 mAbs leads to more stable tracer by decreasing in vivo deiodination and improves the tumor retention of radioiodinated mAbs. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: To date, the only antiangiogenic antibody approved for clinical indications is bevacizumab. There is a need to develop more antibodies that have targets highly expressed on tumor endothelium. CD105 represents a promising marker of angiogenesis, but its therapeutic relevance in cancer needs to be further investigated. In this context, this study suggests the potential use of indirectly iodinated anti-CD105 mAbs for tumor imaging and for therapeutic purposes. PMID- 27179251 TI - Identification of Risk Factors for Bisphosphonate-Associated Atypical Femoral Fractures and Osteonecrosis of the Jaw in a Pharmacovigilance Database. AB - BACKGROUND: Atypical femoral fractures (AFs) and osteonecrosis of the jaw (ONJ) are well-known adverse drug reactions (ADRs) associated with bisphosphonates. To prevent these ADRs and to aid in the search for pathogenic mechanisms, knowledge of risk factors can be helpful. OBJECTIVE: To identify risk factors for bisphosphonate-related ONJ and AF. METHODS: In this case-control study of reports of bisphosphonate-related ADRs from February 16, 1984, to October 16, 2013, in the Swedish national database of ADRs, we compared characteristics for cases of ONJ (n = 167) and AF (n = 55) with all other bisphosphonate-related ADRs (n = 565) with regard to demographic variables, clinical characteristics, and concomitant drug treatments. We adjusted for multiple comparisons with Bonferroni correction. RESULTS: Time to onset of ADRs differed statistically significantly between cases of AF and controls (2156 vs 111 days). For ONJ versus controls, differences were statistically significant for time to onset (1240 vs 111 days), intravenous administration (40% vs 20%), dental procedures (49% vs 0.2%) and prostheses (5% vs 0%), cancer disease (44% vs 12%), multiple myeloma (21% vs 1%), rheumatoid arthritis (14% vs 5%), and treatment with antineoplastic agents and oxycodone. CONCLUSION: These results lend further evidence to previously identified risk factors for ONJ-that is, intravenous bisphosphonate administration; invasive dental procedures and dental prostheses; cancer disease, in particular multiple myeloma; and possibly, long-term bisphosphonate treatment. A putative further risk factor is rheumatoid arthritis. Only long-term bisphosphonate treatment was more common among AF cases. The lack of overlap of risk factors between ONJ and AF suggests different pathogenic mechanisms. PMID- 27179252 TI - A 15-Year Single-Center Experience of Endovascular Repair for Elective and Ruptured Abdominal Aortic Aneurysms. AB - PURPOSE: To evaluate the differences in technical outcomes and secondary interventions between elective endovascular aneurysm repair (el-EVAR) procedures and those for ruptured aneurysms (r-EVAR). METHODS: Of the 906 patients treated with primary EVAR from September 1998 until July 2012, 43 cases were excluded owing to the use of first-generation stent-grafts. Among the remaining 863 patients, 773 (89.6%) patients (mean age 72 years; 697 men) with asymptomatic or symptomatic abdominal aortic aneurysms (AAAs) were assigned to the el-EVAR group; 90 (10.4%) patients (mean age 73 years; 73 men) were assigned to the r-EVAR group based on blood outside the aortic wall on preoperative imaging. The primary study outcome was technical success; secondary endpoints, including freedom from secondary interventions and late survival, were examined with Kaplan-Meier analyses. RESULTS: At baseline, r-EVAR patients had larger aneurysms on average (p<0.001) compared to el-EVAR patients. Technical success was comparable (p=0.052), but there were more type Ia endoleaks at completion angiography in the r-EVAR group (p=0.038). As anticipated, more patients died in the first month in the r-EVAR group (18.9% vs 2.2% el-EVAR, p<0.001). At 5 years, there was an overall survival of 65.1% for the el-EVAR patients vs 48.1% in the r-EVAR group (p<0.001). The freedom from AAA-related mortality was 95.7% for el-EVAR and 71.0% for r-EVAR (p<0.001). Five-year freedom from type I/III endoleaks was significantly lower in the r-EVAR group (78.7% vs 90.0%, p=0.003). Five-year freedom from secondary intervention estimates were not significantly different (el-EVAR 84.2% vs r-EVAR 78.2%, p=0.064). CONCLUSION: Within our cohort of primary EVAR patients, r-EVAR cases showed comparable stent-graft-related technical outcome. Although there was a higher incidence of type Ia endoleaks on completion angiography in the r-EVAR group, the overall secondary intervention rate was comparable to el-EVAR. PMID- 27179253 TI - Statistical lessons learned for designing cluster randomized pragmatic clinical trials from the NIH Health Care Systems Collaboratory Biostatistics and Design Core. AB - BACKGROUND/AIMS: Pragmatic clinical trials embedded within health care systems provide an important opportunity to evaluate new interventions and treatments. Networks have recently been developed to support practical and efficient studies. Pragmatic trials will lead to improvements in how we deliver health care and promise to more rapidly translate research findings into practice. METHODS: The National Institutes of Health (NIH) Health Care Systems Collaboratory was formed to conduct pragmatic clinical trials and to cultivate collaboration across research areas and disciplines to develop best practices for future studies. Through a two-stage grant process including a pilot phase (UH2) and a main trial phase (UH3), investigators across the Collaboratory had the opportunity to work together to improve all aspects of these trials before they were launched and to address new issues that arose during implementation. Seven Cores were created to address the various considerations, including Electronic Health Records; Phenotypes, Data Standards, and Data Quality; Biostatistics and Design Core; Patient-Reported Outcomes; Health Care Systems Interactions; Regulatory/Ethics; and Stakeholder Engagement. The goal of this article is to summarize the Biostatistics and Design Core's lessons learned during the initial pilot phase with seven pragmatic clinical trials conducted between 2012 and 2014. RESULTS: Methodological issues arose from the five cluster-randomized trials, also called group-randomized trials, including consideration of crossover and stepped wedge designs. We outlined general themes and challenges and proposed solutions from the pilot phase including topics such as study design, unit of randomization, sample size, and statistical analysis. Our findings are applicable to other pragmatic clinical trials conducted within health care systems. CONCLUSION: Pragmatic clinical trials using the UH2/UH3 funding mechanism provide an opportunity to ensure that all relevant design issues have been fully considered in order to reliably and efficiently evaluate new interventions and treatments. The integrity and generalizability of trial results can only be ensured if rigorous designs and appropriate analysis choices are an essential part of their research protocols. PMID- 27179254 TI - Lipoxin A4 Is Increased in the Plasma of Preeclamptic Women. AB - BACKGROUND: Excessive inflammation is involved in preeclampsia (PE) pathogenesis. Lipoxin A4 (LXA4) is an eicosanoid that counter-regulates inflammation. The main objective of this study was to determine LXA4 plasma levels in PE women. The correlations among LXA4 levels, ultrasensitive C-reactive protein (us-CRP) levels, and clinical/laboratory parameters of the studied participants were also investigated. METHODS: LXA4 plasma levels were determined by ELISA in 23 nonpregnant, 26 normotensive pregnant, and 27 PE women (early PE (N = 10) and late PE (N = 17)), according to gestational age (GA) at clinical symptoms onset). The clinical/laboratory parameters included in Spearman's correlation analysis were: systolic and diastolic blood pressure (SBP and DBP, respectively), lactate dehydrogenase (LDH) activity, platelet count, proteinuria, and white blood cell count (WBC). RESULTS: LXA4 levels were higher in PE women than in nonpregnant and normotensive pregnant women, and similar between nonpregnant and normotensive pregnant women. LXA4 plasma levels were higher in early PE vs. normotensive pregnancy (GA < 34 weeks) and in late PE vs. normotensive pregnancy (GA >= 34 weeks). No significant differences were detected between early and late PE. LXA4 levels were positively correlated with us-CRP levels, SBP, DBP, and WBC. No significant correlation was detected between LXA4 levels and the other laboratory parameters. CONCLUSIONS: Chronic inflammation in PE, in spite of increased levels of LXA4, points to a possible failure in this regulatory pathway. Further studies are necessary to clarify this issue and to evaluate the role of LXA4 and other proresolving mediators of inflammation in the pathogenesis of PE. PMID- 27179255 TI - The Expanding Role of Audiology Telepractice. PMID- 27179256 TI - A Phoneme Perception Test Method for High-Frequency Hearing Aid Fitting. AB - BACKGROUND: Outcomes with hearing aids (HAs) can be assessed using various speech tests, but many tests are not sensitive to changes in high-frequency audibility. PURPOSE: A Phoneme Perception Test (PPT), designed for the phonemes /s/ and /?/, has been developed to investigate whether detection and recognition tasks are able to measure individual differences in phoneme audibility and recognition for various hearing instrument settings. These capabilities were studied using two different fricative stimulus materials. The first set of materials preserves natural low-level sound components in the low- and mid-frequency ranges (LF set); the second set of materials attempts to limit the audibility to high-frequency fricative noise (nLF set). To study the effect on phoneme detection and recognition when auditory representations of /s/ and /?/ are modified, a too strong nonlinear frequency compression (NLFC) setting was applied. RESEARCH DESIGN: Repeated measure design was used under several different conditions. STUDY SAMPLE: A total of 31 hearing-impaired individuals participated in this study. Of the 31 participants, 10 individuals did not own HAs but were provided with them during the study and 21 individuals owned HAs and were experienced users. All participants had a symmetrical sensorineural hearing loss. DATA COLLECTION AND ANALYSIS: The present study applied a phoneme detection test and a recognition test with two different stimulus sets under different amplification conditions. The statistical analysis focused on the capability of the PPT to measure the effect on audibility and perception of high-frequency information with and without HAs, and between HAs with two different NLFC settings ("default" and "too strong"). RESULTS: Detection thresholds (DTs) and recognition thresholds (RTs) were compared with respective audiometric thresholds in the free field for all available conditions. Significant differences in thresholds between LF and nLF stimuli were observed. The thresholds for nLF stimuli showed higher correlation to the corresponding audiometric thresholds than the thresholds for LF stimuli. The difference in thresholds for unaided and aided conditions was larger for the stimulus set nLF than for the stimulus set LF. Also, thresholds were similar in both aided conditions for stimulus set LF, whereas a large difference between amplifications was observed for the stimulus set nLF. When NLFC was set "too strong," DTs and RTs differed significantly for /s/. CONCLUSIONS: The findings from this study strongly suggest that measuring DTs and RTs with the stimulus set nLF is beneficial and useful to quantify the effects of HAs and NLFC on high-frequency speech cues for detection and recognition tasks. The findings also suggest that both tests are necessary because they assess audibility as well as recognition abilities, particularly as they relate to speech modification algorithms. The experiments conducted in this study did not allow for any acclimatization of the participants to increased high-frequency gain or NLFC. Further investigations should therefore examine the impact on DTs and RTs in the PPT as well as the contrasting effects of strong setting of NLFC to DTs and RTs because of (re)learning of modified auditory representations of /s/ and /?/ as caused by NLFC. PMID- 27179257 TI - The Effect of the Arabic Computer Rehabilitation Program "Rannan" on Sound Detection and Discrimination in Children with Cochlear Implants. AB - PURPOSE: The aim of this work is to examine the efficacy of using computer-based training program (Rannan) as an intervention approach to enhance sound detection and discrimination in Arabic-speaking children with cochlear implants (CIs). RESEARCH DESIGN: A prospective study comparing performance between two groups of children. Participants were divided into two equal groups that were matched in age and programming strategies. Group I received the traditional clinic-based therapy and group II received the same traditional therapy approach in addition to a computer-based program. STUDY SAMPLE: A total of 26 children with CIs in the age range of 3-6.5 yr were recruited from King Abdulaziz University Hospital. DATA COLLECTION AND ANALYSIS: Listening Progress Profile and Infant-Toddler Meaningful Integration Scale were used preoperatively, and to compare performance between the two groups at 1-, 3-, 6-, and 12-mo after device-fitting. Data were subjected to mixed analysis of variance. RESULTS: Both assessment tools (Listening Progress Profile and Infant-Toddler Meaningful Integration Scale) revealed that group II scored higher than group I. CONCLUSION: The study demonstrated that using computer-based training in addition to the traditional rehabilitation therapy can serve as a facilitative tool to enhance the benefit achieved from CI. PMID- 27179258 TI - Recognition of Speech from the Television with Use of a Wireless Technology Designed for Cochlear Implants. AB - BACKGROUND: Cochlear implant (CI) recipients often experience difficulty understanding speech in noise and speech that originates from a distance. Many CI recipients also experience difficulty understanding speech originating from a television. Use of hearing assistance technology (HAT) may improve speech recognition in noise and for signals that originate from more than a few feet from the listener; however, there are no published studies evaluating the potential benefits of a wireless HAT designed to deliver audio signals from a television directly to a CI sound processor. PURPOSE: The objective of this study was to compare speech recognition in quiet and in noise of CI recipients with the use of their CI alone and with the use of their CI and a wireless HAT (Cochlear Wireless TV Streamer). RESEARCH DESIGN: A two-way repeated measures design was used to evaluate performance differences obtained in quiet and in competing noise (65 dBA) with the CI sound processor alone and with the sound processor coupled to the Cochlear Wireless TV Streamer. STUDY SAMPLE: Sixteen users of Cochlear Nucleus 24 Freedom, CI512, and CI422 implants were included in the study. DATA COLLECTION AND ANALYSIS: Participants were evaluated in four conditions including use of the sound processor alone and use of the sound processor with the wireless streamer in quiet and in the presence of competing noise at 65 dBA. Speech recognition was evaluated in each condition with two full lists of Computer Assisted Speech Perception Testing and Training Sentence-Level Test sentences presented from a light-emitting diode television. RESULTS: Speech recognition in noise was significantly better with use of the wireless streamer compared to participants' performance with their CI sound processor alone. There was also a nonsignificant trend toward better performance in quiet with use of the TV Streamer. Performance was significantly poorer when evaluated in noise compared to performance in quiet when the TV Streamer was not used. CONCLUSIONS: Use of the Cochlear Wireless TV Streamer designed to stream audio from a television directly to a CI sound processor provides better speech recognition in quiet and in noise when compared to performance obtained with use of the CI sound processor alone. PMID- 27179259 TI - Assessment of Functional Hearing in Greek-Speaking Children Diagnosed with Central Auditory Processing Disorder. AB - BACKGROUND: Including speech recognition in noise testing in audiological evaluations may reveal functional hearing deficits that may otherwise remain undetected. PURPOSE: The current study explored the potential utility of the Speech-in-Babble (SinB) test in the assessment of central auditory processing disorder (CAPD) in young children for whom diagnosis is challenging. RESEARCH DESIGN: A cross-sectional analysis. STUDY SAMPLE: Forty-one Greek children 4-13 yr of age diagnosed with CAPD and exhibiting listening and academic problems (clinical group) and 20 age-matched controls with no listening or academic problems participated in the study. DATA COLLECTION AND ANALYSIS: All participants' auditory processing was assessed using the same tests and instrumentation in a sound-treated room. Two equivalent lists of the SinB test, developed at the Psychoacoustic Laboratory of the Aristotle University of Thessaloniki, were administered monaurally in a counterbalanced order. SinB consists of lists of 50 phonetically balanced disyllabic words presented in background multitalker babble. Five signal-to-noise ratios (SNRs) were used in a fixed order. The children were instructed to repeat the word after each presentation. The SNR at which the child achieved 50% correct word identification served as the dependent variable or outcome measure, with higher SinB scores (measured in SNR dB) corresponding to poorer performance. RESULTS: SinB performance was better (lower SNR) for the normal control group versus the clinical group [F(1,35) = 43.03, p < 0.0001]. SinB inversely correlated with age for both CAPD and control groups (r = -0.648, p << 0.001 and r = -0.658, p < 0.005, respectively). Regression analysis revealed that linear models better explained the variance in the data than a quadratic model for both the control and CAPD groups. The slope (beta value of the linear model) was steeper for the clinical group compared to the control group (beta = -0.306 versus beta = -0.130, respectively). An analysis of covariance run with age as the covariate to assess the potential effect of comorbidity on SinB performance in children with CAPD with and without comorbid conditions revealed no significant differences between groups [F(1,38) = 0.149, p > 0.05]. CONCLUSIONS: This study offers the first detailed presentation of the performance of Greek children on a Greek language SinB test. The main finding is that SinB scores improved as a function of age in a constant manner as represented by the slope of the linear regression line for both CAPD and control groups. Results suggest that this speech recognition in competition test holds promise for differentiating typically developing Greek children from those children with CAPD across the age range studied here (4-13 yr). The SinB seemed rather immune to the presence of comorbid conditions presented by some of the children in this study, suggesting its potential utility as a valid measure of central auditory processing. While there are many speech-in noise or competition tests in English, there are fewer in other languages. Tests like the SinB should be developed in other languages to ensure that children demonstrating "listening" problems can be properly evaluated. PMID- 27179260 TI - Cortical Auditory-Evoked Potentials in Response to Multitone Stimuli in Hearing Impaired Adults. AB - PURPOSE: To determine if one-octave multitone (MT) stimuli increase the amplitude of cortical auditory-evoked potentials (CAEPs) in individuals with a hearing loss when compared to standard pure-tone (PT) stimuli and narrow-band noise (NBN). RESEARCH DESIGN: CAEPs were obtained from 16 hearing-impaired adults in response to PT and MT auditory stimuli centered around 0.5, 1, 2, and 4 kHz and NBN centered around 1 and 2 kHz. Hearing impairment ranged from a mild to a moderate hearing loss in both ears. Auditory stimuli were monaurally delivered through insert earphones at 10 and 20 dB above threshold. The root mean square amplitude of the CAEP and the detectability of the responses using Hotelling's T2 were calculated and analyzed. RESULTS: CAEP amplitudes elicited with MT stimuli were on average 29% larger than PT stimuli for frequencies centered around 1, 2, and 4 kHz. No significant difference was found for responses to 0.5-kHz stimuli. Significantly higher objective detection scores were found for MT when compared to PT. For the 1- and 2-kHz stimuli, the CAEP amplitudes to NBN were not significantly different to those evoked by PT but a significant difference was found between MT stimuli and both NBN and PT. The mean detection sensitivity of MT for the four frequencies was 80% at 10 dB SL and 95% at 20 dB SL, and was comparable with detection sensitivities observed in normal-hearing participants. CONCLUSIONS: Using MT stimuli when testing CAEPs in adults with hearing impairment showed larger amplitudes and a higher objective detection sensitivity compared to using traditional PT stimuli for frequencies centered around 1, 2, and 4 kHz. These findings suggest that MT stimuli are a clinically useful tool to increase the efficiency of frequency-specific CAEP testing in adults with hearing impairment. PMID- 27179261 TI - Validation of the Home Hearing TestTM. AB - BACKGROUND: The Home Hearing TestTM (HHT) is an automated pure-tone threshold test that obtains an air-conduction audiogram at five test frequencies. It was developed to provide increased access to hearing testing and support home telehealth programs. PURPOSE: The study was conducted as part of an audiology telehealth trial based at the U.S. Department of Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN. Air-conduction audiograms obtained by the HHT were compared to results obtained in the clinic. RESEARCH DESIGN: Prospective, repeated measures. STUDY SAMPLE: Twenty-eight participants, aged 44 88 yr (mean = 65) were recruited from the Nashville U.S. Department of Veterans Affairs audiology clinic. Participants were required to have a Windows personal computer in the home and were self-reported to be comfortable with using computers. Two participants had normal hearing and 26 had hearing loss of various severities and configurations. DATA COLLECTION AND ANALYSIS: Audiograms were obtained in the audiology clinic by experienced audiologists following standard clinical protocols. Participants were provided with a kit for installing HHT on their home computers. The HHT air-conduction audiogram is obtained with Automated Method for Testing Auditory Sensitivity (AMTAS((r))), described in previous publications. Threshold pairs (clinic versus HHT) were analyzed by determining distributions of threshold differences and absolute differences. These were compared to distributions of differences between manual threshold pairs obtained by two audiologists and AMTAS((r)) versus manual threshold pairs obtained under laboratory conditions. RESULTS: Threshold differences (clinic versus HHT) were slightly larger than differences between thresholds obtained by two audiologists and AMTAS((r)) versus manual threshold differences obtained under laboratory conditions. The differences were not statistically significant. CONCLUSIONS: HHT air-conduction audiograms agree well with audiograms obtained in the clinic. HHT is well suited to home telehealth applications and personal use. PMID- 27179262 TI - How Tobacco Companies are Perceived Within the United Kingdom: An Online Panel. AB - INTRODUCTION: Little is known about how consumers perceive tobacco companies in the United Kingdom. METHODS: An online cross-sectional survey with those aged 16 years and over (N = 2253) explored perceptions of, and attitudes towards, tobacco companies. This included awareness of tobacco companies, views on tobacco companies' practices (targeting the most vulnerable, encouraging smoking to replace those who quit or die, making cigarettes more addictive) and values (honesty, ethics, interest in harm reduction), perceptions of regulation of tobacco companies (whether tobacco companies have the same marketing rights as other companies, should be allowed to promote cigarettes, be required to sell cigarettes in plain packs, and pay for associated health costs), and locus of responsibility for health problems caused by tobacco use. RESULTS: Prompted awareness of tobacco companies was high (68%). Almost a third of the sample had a negative perception of tobacco companies' practices, for example, they thought they made cigarettes more addictive. In terms of tobacco companies' values, less than a fifth considered tobacco companies honest, ethical, and interested in reducing the harm caused by cigarettes. Indeed, tobacco company executives were rated lower than the seven other professions asked about, except car salesman, in terms of ethics and honesty. More than half the sample supported greater regulation, for example, requiring tobacco companies to pay for health costs due to tobacco use. Most attributed responsibility for smoking-related health problems to smokers (88%) and tobacco companies (55%). CONCLUSIONS: The findings suggest that consumers are not fully informed about tobacco company practices. IMPLICATIONS: Few studies outside of North America have explored perceptions of tobacco companies' practices, values and regulation and responsibility for smoking-related illness. Adults surveyed within the United Kingdom considered tobacco companies dishonest, unethical and untrustworthy, but only a third of the sample thought that they encourage new smokers or have made cigarettes more addictive, and just over a half attributed most of the responsibility for smoking related health problems to tobacco companies. As consumers do not appear fully informed about the role of tobacco companies in initiating and perpetuating the tobacco epidemic, tobacco industry denormalization campaigns may be of potential value. PMID- 27179263 TI - Does anti-Mullerian hormone predict menopause in the general population? Results of a prospective ongoing cohort study. AB - STUDY QUESTION: Do ovarian reserve tests (ORTs) predict age at natural menopause (ANM) in a cohort of healthy women with a regular menstrual cycle? SUMMARY ANSWER: Of the ORTs researched, anti-Mullerian hormone (AMH) alone predicts age at menopause. However, its predictive value decreased with increasing age of the woman, prediction intervals were broad and extreme ages at menopause could not be predicted. WHAT IS KNOWN ALREADY: A fixed interval is hypothesized to exist between ANM and age at loss of natural fertility. Therefore, if it is possible to predict ANM, one could identify women destined for early menopause and thus at higher risk for age-related subfertility. Of ORTs researched in the prediction of ANM, AMH is the most promising one. STUDY DESIGN, STUDY SIZE AND DURATION: A long term, extended follow-up study was conducted, results of the first follow-up round were previously published. Two hundred and sixty-five normo-ovulatory women (21-46 years) were included between 1992 and 2001, 49 women (18.5%) could not be reached in the current follow-up round. PARTICIPANTS, SETTING, METHODS: Two hundred and sixty-five healthy normo-ovulatory women were included, recruited in an Academic hospital. We measured baseline AMH, follicle-stimulating hormone and the antral follicle count (AFC). At follow-up (2009 and 2013), menopausal status was determined via questionnaires. Cox regression analysis calculated time to menopause (TTM) using age and ORT. A check of (non-) proportionality of the predictive effect of AMH was performed. A Weibull survival model was used in order to predict individual ANM. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 155 women were available for analyses. Eighty-one women (37.5%) had become post menopausal during follow-up. Univariable Cox regression analysis demonstrated age and ORTs to be significantly correlated with TTM. Multivariable Cox regression analysis, adjusting for baseline age and smoking; however, demonstrated AMH alone to be an independent predictor of TTM (Hazard Ratio 0.70, 95% Confidence Interval 0.56-0.86, P-value <0.001). A (non-)proportionality analysis of AMH over time demonstrated AMH's predictive effect to decline over time. LIMITATIONS, REASON FOR CAUTION: The observed predictive effect of AMH became less strong with increasing age of the woman. Individual AMH-based age at menopause predictions did not cover the full range of menopausal ages, but did reduce the variation around the predicted ANM from 20 to 10.1 years. WIDER IMPLICATIONS OF THE FINDINGS: Age-specific AMH levels are predictive for ANM. Unlike in our previous publication however, a declining AMH effect with increasing age was observed. This declining AMH effect is in line with recent long-term follow-up data published by others. Moreover, the accompanying predictive inaccuracy observed in individual age at menopause predictions based on AMH, makes this marker currently unsuitable for use in clinical practice. STUDY FUNDING/COMPETING INTERESTS: No external funds were used for this study. M.D., M.J.C.E, S.L.B., G.J.S. and I.A.J.R. have nothing to declare. J.S.E.L. has received fees and grant support from the following companies (in alphabetical order): Ferring, Merck-Serono, MSD, Organon, Serono and Schering Plough. F.J.M.B. receives monetary compensation: member of the external advisory board for Merck Serono, the Netherlands; consultancy work for Gedeon Richter, Belgium; educational activities for Ferring BV, the Netherlands; strategic cooperation with Roche on automated AMH assay development. PMID- 27179264 TI - Bisphenol A in culture media and plastic consumables used for ART. AB - STUDY QUESTION: Do the embryo culture media and plastic materials used during assisted reproductive technology (ART) laboratory procedures expose embryos to bisphenol A (BPA)? SUMMARY ANSWER: BPA was not detected in embryo culture media or protein supplements at concentrations above those encountered in normal patient serum and follicular fluids. WHAT IS KNOWN ALREADY: BPA is strongly suspected of altering the epigenome during mammalian development. Medical devices have been shown to be a source of BPA exposure in adult and neonatal intensive care units. STUDY DESIGN, SIZE, DURATION: An analytical study of ART culture media and plastic labware products was performed under conditions close to routine practice and if BPA was detected, tests were carried out under more stringent conditions. PARTICIPANTS/MATERIALS, SETTING, METHODS: Two single-step embryo culture media, two sequential media and three different protein supplements [a purified human serum albumin (HSA), a synthetic serum substitute, and a recombinant HSA] were tested for BPA. Thirty-three different plastic consumables, used from oocyte collection through to embryo transfer, were tested for their ability to leach BPA into their surrounding environment.BPA concentrations were measured according to a previously described liquid chromatography/mass spectrometry method. This method is linear over the calibration range from 0.5 to 100 ng/ml using a linear model weighted by 1/X2 and validated in terms of selectivity, linearity, repeatability, reproducibility and limit of quantification (0.5 ng/ml). MAIN RESULTS AND THE ROLE OF CHANCE: Neither the culture media nor the protein supplements were shown to contain detectable levels of BPA. None of the plastic materials leached BPA into the surrounding medium at levels higher than the upper limit detected previously in serum and follicular fluids in women (about 2 ng/ml). However, the plastic of the three tested strippers used for oocyte denudation/embryo handling did contain BPA. Two of these strippers are made with polycarbonate, a plastic whose synthesis is known to require BPA. LIMITATIONS, REASONS FOR CAUTION: This study is limited to the ART media and materials tested here and using a BPA assay with a limit of quantification at 0.5 ng/ml. A minimum volume was required for testing, and one type of plastic labware could not be tested in conditions identical to those in routine use. WIDER IMPLICATIONS OF THE FINDINGS: Although we demonstrated that some plastic materials used in ART contain BPA, under routine conditions none appear capable of leaching BPA at levels higher than those from maternal internal exposure. However, BPA is strongly suspected of altering the epigenome. Since important epigenetic modifications occur in the early embryonic stage, it is questionable whether plastics that contain BPA, polycarbonate in particular, should be used in the manufacture of plastic consumables for ART procedures. STUDY FUNDING/COMPETING INTERESTS: This work was supported by a grant from the Agence de Biomedecine (AOR 2012) and by a grant from the French Ministry of Health (Clinical Research Hospital Program 2012; no.12-018-0560). The authors declared no competing interest. PMID- 27179266 TI - In memoriam Professor Aleksandra Krygier-Stojalowska (2.10.1923 - 17.11.2015). PMID- 27179265 TI - A randomized controlled, non-inferiority trial of modified natural versus artificial cycle for cryo-thawed embryo transfer. AB - STUDY QUESTION: Are live birth rates (LBRs) after artificial cycle frozen-thawed embryo transfer (AC-FET) non-inferior to LBRs after modified natural cycle frozen thawed embryo transfer (mNC-FET)? SUMMARY ANSWER: AC-FET is non-inferior to mNC FET with regard to LBRs, clinical and ongoing pregnancy rates (OPRs) but AC-FET does result in higher cancellation rates. WHAT IS ALREADY KNOWN: Pooling prior retrospective studies of AC-FET and mNC-FET results in comparable pregnancy and LBRs. However, these results have not yet been confirmed by a prospective randomized trial. STUDY DESIGN, SIZE AND DURATION: In this non-inferiority prospective randomized controlled trial (acronym 'ANTARCTICA' trial), conducted from February 2009 to April 2014, 1032 patients were included of which 959 were available for analysis. The primary outcome of the study was live birth. Secondary outcomes were clinical and ongoing pregnancy, cycle cancellation and endometrium thickness. A cost-efficiency analysis was performed. PARTICIPANT/MATERIALS, SETTING, METHODS: This study was conducted in both secondary and tertiary fertility centres in the Netherlands. Patients included in this study had to be 18-40 years old, had to have a regular menstruation cycle between 26 and 35 days and frozen-thawed embryos to be transferred had to derive from one of the first three IVF or IVF-ICSI treatment cycles. Patients with a uterine anomaly, a contraindication for one of the prescribed medications in this study or patients undergoing a donor gamete procedure were excluded from participation. Patients were randomized based on a 1:1 allocation to either one cycle of mNC-FET or AC-FET. All embryos were cryopreserved using a slow-freeze technique. MAIN RESULTS AND THE ROLE OF CHANCE: LBR after mNC-FET was 11.5% (57/495) versus 8.8% in AC-FET (41/464) resulting in an absolute difference in LBR of -0.027 in favour of mNC-FET (95% confidence interval (CI) -0.065-0.012; P = 0.171). Clinical pregnancy occurred in 94/495 (19.0%) patients in mNC-FET versus 75/464 (16.0%) patients in AC-FET (odds ratio (OR) 0.8, 95% CI 0.6-1.1, P = 0.25). 57/495 (11.5%) mNC-FET resulted in ongoing pregnancy versus 45/464 (9.6%) AC-FET (OR 0.7, 95% CI 0.5-1.1, P = 0.15). chi(2) test confirmed the lack of superiority. Significantly more cycles were cancelled in AC-FET (124/464 versus 101/495, OR 1.4, 95% CI 1.1-1.9, P = 0.02). The costs of each of the endometrial preparation methods were comparable (?617.50 per cycle in NC-FET versus ?625.73 per cycle in AC-FET, P = 0.54). LIMITATIONS, REASONS FOR CAUTION: The minimum of 1150 patients required for adequate statistical power was not achieved. Moreover, LBRs were lower than anticipated in the sample size calculation. WIDER IMPLICATIONS OF THE FINDINGS: LBRs after AC-FET were not inferior to those achieved by mNC-FET. No significant differences in clinical and OPR were observed. The costs of both treatment approaches were comparable. STUDY FUNDING/COMPETING INTERESTS: An educational grant was received during the conduct of this study. Merck Sharpe Dohme had no influence on the design, execution and analyses of this study. E.R.G. received an education grant by Merck Sharpe Dohme (MSD) during the conduct of the present study. B.J.C. reports grants from MSD during the conduct of the study. A.H. reports grants from MSD and Ferring BV the Netherlands and personal fees from MSD. Grants from ZonMW, the Dutch Organization for Health Research and Development. J.S.E.L. reports grants from Ferring, MSD, Organon, Merck Serono and Schering-Plough during the conduct of the study. F.J.M.B. receives monetary compensation as member of the external advisory board for Merck Serono, consultancy work for Gedeon Richter, educational activities for Ferring BV, research cooperation with Ansh Labs and a strategic cooperation with Roche on automated anti Mullerian hormone assay development. N.S.M. reports receiving monetary compensations for external advisory and speaking work for Ferring BV, MSD, Anecova and Merck Serono during the conduct of the study. All reported competing interests are outside the submitted work. No other relationships or activities that could appear to have influenced the submitted work. TRIAL REGISTRATION NUMBER: Netherlands trial register, number NTR 1586. TRIAL REGISTRATION DATE: 13 January 2009. FIRST PATIENT INCLUDED: 20 April 2009. PMID- 27179267 TI - Review of succinate dehydrogenase-deficient renal cell carcinoma with focus on clinical and pathobiological aspects. AB - Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) was first identified in 2004 and has been integrated into the 2016 WHO classification of RCC. Succinate dehydrogenase (SDH) is an enzyme complex composed of four protein subunits (SDHA, SDHB, SDHC and SDHD). The tumor which presents this enzyme mutation accounts for 0.05 to 0.2% of all renal carcinomas. Multiple tumors may occur in approximately 30% of affected patients. SDHB-deficient RCC is the most frequent, and the tumor histologically consists of cuboidal cells with eosinophilic cytoplasm, vacuolization, flocculent intracytoplasmic inclusion and indistinct cell borders. Ultrastructurally, the tumor contains abundant mitochondria. Immunohistochemically, tumor cells are positive for SDHA, but negative for SDHB in SDHB-, SDHC- and SDHD-deficient RCCs. However, SDHA deficient RCC shows negativity for both SDHA and SDHB. In molecular genetic analyses, a germline mutation in the SDHB, SDHC or SDHD gene (in keeping with most patients having germline mutations in an SDH gene) has been identified in patients with or without a family history of renal tumors, paraganglioma/pheochromocytoma or gastrointestinal stromal tumor. While most tumors are low grade, some tumors may behave in an aggressive fashion, particularly if they are high nuclear grade, and have coagulative necrosis or sarcomatoid differentiation. PMID- 27179268 TI - Influence of gross specimen sampling on the incidence of incidental prostatic carcinoma in cystoprostatectomy specimens of patients with bladder carcinoma. AB - Reported prostate cancer incidence rates vary greatly among cystoprostatectomy samples. We investigated how the thoroughness of prostate sampling influences prostatic carcinoma incidence in bladder cancer patients. In a retrospective study, 313 cystoprostatectomy cases of urinary bladder carcinoma were analysed for the presence of concurrent prostatic carcinoma. Patients were divided into two groups: patients who had undergone the operation before and after 2007, when a policy of preferably complete prostate sampling in cystoprostatectomy specimens was introduced at our institution. Cases processed after the 2007 recommended sampling changes had a significantly higher rate of incidental prostatic carcinoma and clinically significant prostatic carcinoma than the pre-2007 group (p < 0.0001 and p = 0.003, respectively). Complete prostate processing in cystoprostatectomy specimens results in a higher incidence of incidental prostatic carcinoma than with partial processing. More patients with clinically significant prostate cancer are consequently discovered. In conclusion, we believe that complete prostate sampling should be mandatory. PMID- 27179269 TI - Concordance of KRAS mutation status between luminal and peripheral regions of primary colorectal cancer. A laser-capture microdissection-based study. AB - The presence of KRAS mutation in colorectal cancer (CRC) is a marker of resistance to anti-EGFR therapy. However, there are conflicting reports concerning intratumoral heterogeneity of KRAS mutations. The aim of this study was to determine whether within primary CRCs with KRAS mutations intratumoral KRAS mutation heterogeneity can be detected between two strictly defined areas, i.e. the luminal (mucosa/submucosa) and peripheral invasive front of the tumor. Using laser-capture microdissection, from every tumor about 400-500 nests of cancer cells were excised from each of the examined areas (luminal and peripheral) and PNAClamp, a high-sensitivity real-time PCR-based diagnostic assay for KRAS mutation testing, was used for molecular analysis. KRAS mutations were detected in codon 12 in both luminal and peripheral regions in all tumors examined. We conclude that from the point of view of practical KRAS mutation testing for predictive purposes in patients with CRC (i.e. testing mutations in codons 12 and 13) sampling errors are unlikely to occur if in CRCs with KRAS mutations only the luminal (as in biopsy tissue) or peripheral region is examined, provided a sensitive system of detection is applied and an appropriate number of tumor cells with minimal contamination by benign cells is analyzed. PMID- 27179270 TI - The diagnosis of cancer in thyroid fine needle aspiration biopsy. Surgery, repeat biopsy or specimen consultation? AB - Fine needle aspiration biopsy (FNA) is the only diagnostic method that allows a preoperative diagnosis of thyroid carcinoma. An unequivocal diagnosis of a malignant change is achievable only in cases in which all cytological criteria of carcinoma are met. The aim of the study was to evaluate the necessity of repeat thyroid FNA in patients with papillary thyroid carcinoma verified on consultative examination (CE). We analyzed cytology reports of thyroid FNA and CE that resulted in the diagnosis of papillary carcinoma. Evaluation of the correlation of the cytological diagnosis with the histopathology report was based on data obtained after the surgery. Between 2010 and 2015 in the Institute of Oncology (IO) there were 184 cancers diagnosed on CE or in thyroid FNA performed primarily in IO. Additionally, 74 patients were subjected to repeat biopsy after confirmation of cancer in CE. Histopathological diagnosis of cancer was obtained in 62 (100%) cases that were doubly confirmed with cytological examination. The remaining 12 patients were operated on outside the institute. From 110 FNA primarily performed in the IO, histopathological verification was achievable in 92 cases, from which 92 (100%) provided a confirmation of cancer, and the remaining 18 patients were operated on outside the institute. High (100%) specificity of cancer diagnosis in FNA established primarily and verified on CE (second independent assessment) indicates that repeat FNA in order to confirm the diagnosis is unnecessary. PMID- 27179271 TI - Correspondence of cytological and histopathological diagnoses in diagnostic category V of the Bethesda system: "suspicious for malignancy". AB - The progress in imaging methods enables fine needle aspiration (FNA) biopsy to be performed on smaller and smaller lesions, including malignant ones (papillary microcarcinomas). The follicular variant predominates in this group, with cytological features often not permitting an unbiased interpretation. The aim of the study was to determine the degree of reliability of the "suspicious for malignancy" (SM) diagnosis in material from the Institute of Oncology in Gliwice (IO). 290 primary SM diagnoses were established from 2010 to 2015 in the IO, including the consultations. None of the patients was treated surgically after the first FNA resulting in diagnostic category V (DC V). After the second FNA 80 patients underwent surgery, after the third 58, and after subsequent FNA 10. Together, 148 surgical resections were performed. Among 148 patients treated surgically, 111 were diagnosed with malignant lesions, which constitutes 75%. Predominantly - in 91 cases - the histopathological outcome was papillary carcinoma. The others were: 16 medullary carcinomas, 2 follicular carcinomas, and 2 poorly differentiated carcinoma cases. Moreover, 8 follicular adenomas and 28 nonneoplastic lesions were found. The high positive predictive value (PPV = 75%) of SM diagnosis established in the IO testifies to the high reliability of this test. Diagnostic category V in FNA should be an indication for surgical treatment. PMID- 27179272 TI - Gastric hyperplastic polyps coexisting with early gastric cancers, adenoma and neuroendocrine cell hyperplasia. AB - Gastric hyperplastic polyps (GHP) constitute up to 93% of all benign epithelial polyps of the stomach. The average probability of malignant transformation in GHP is 0.6-22% in large series. The aim of the study was to present the coexistence of GHP with early gastric cancer (EGC), gastric adenoma (GA), neuroendocrine cell hyperplasia (NH) and well-differentiated neuroendocrine tumour (NET G1). Three cases were studied to reveal clinical data and morphological changes and to assess the relationship between GHP and accompanying gastric neoplastic lesions. PMID- 27179273 TI - Renal clear cell carcinoma metastasis to salivary glands - a series of 9 cases: clinico-pathological study. AB - Metastatic tumors involving salivary glands arising from the non-head and neck area are very rare. Renal cell carcinoma (RCC) is known for its high propensity for metastasis to unusual localizations. RCC metastasis to the maxillofacial area is an uncommon event (16%), but metastasis to salivary glands is extremely rare. We report a series of 9 such cases retrieved from two institutions. The group included 6 females and 3 males. The age at diagnosis ranged from 60 to 97 years (mean 72.6 years). The tumors involved the parotid gland in 7 cases, and the submandibular and small salivary gland of the oral cavity in 1 case each. The size of tumors ranged from 0.4 to 5 cm. Total parotidectomy with selective neck dissection was performed in 4 cases, while superficial parotidectomy was performed in 1 case and simple resection in 3 cases. Histologically, all the tumors were clear cell renal cell carcinomas, and therefore the differential diagnosis mainly included clear cell variants of salivary gland carcinomas. The parotid gland was the initial manifestation of renal malignancy in 4 of the cases, while in the remaining 5 cases a history of RCC had been known. The salivary gland involvement developed from 11 months to 13 years after the time of diagnosis of the primary tumor. In 2 cases it was the first site of dissemination. Pathologists need to maintain a high index of suspicion for the possibility of metastasis when confronted with oncocytic or clear cell neoplasms developing in salivary glands. RCC, although rare, should be included in this differential diagnosis. PMID- 27179274 TI - Heterogeneous vascular patterns in renal cell carcinomas. AB - The present study proposes a classification of renal cancer tumor blood vessels according to their morphology and maturation grade. We identified four vascular patterns: reticular, diffuse, fasciculated and trabecular. The reticular pattern was present in 63% of cases, being characterized by the predominance of mature CD34+/SMAct+ tumor vessels, highly interconnected. For this pattern, 74% of cases had vascular invasion, and a significant correlation was observed between tumor grade and immature state of tumor vessels (p = 0.022). The diffuse pattern was observed in 23% of cases and was characterized by non-interconnected vessels predominantly of mature CD34+/SMAct+ type and vascular invasion in 64% of cases. Only 8% of cases, had a fasciculate model of vessels distribution, all of them being of mature type, located in the connective axis of papillary renal tumors. For this pattern vascular invasion was found in 50% of cases. In 6% of cases a trabecular pattern was observed and the lowest rate of vascular invasion was registered. We defined here four distinct vascular patterns in renal cell carcinomas showing a strong impact on vascular invasion. A complete morphological and molecular characterization of tumor vessels would be beneficial in elucidating the mechanisms that underlie the ineffectiveness of antiangiogenic/antitumor therapies. PMID- 27179275 TI - Immunohistochemical investigation of endometrial leukocytes in implantation period in rats with streptozotosin-induced diabetes. AB - Our first aim was to determine the total leukocyte profile in implantation. Second aim was to detect the changes in uterine leukocyte profile in diabetes, a common accompanying disease. For this purpose 4 groups are formed with Wistar albino rats weighing 250-300 g. Two of the groups were non-diabetic and two of them were diabetic. One of the diabetic and one of the non-diabetic groups were left pregnant. Then uterus tissues of pregnant animals were removed in the 5th and 7th days of pregnancy together with tissues of other two non-pregnant groups. Tissues were analyzed immunohistochemically with antibodies CD45, CD3, CD4, CD8, CD56, CD68 and CD79a. It was revealed that pregnancy increased immune staining of CD68, CD3, CD45 and CD56 in endometrium. In addition it was observed that immune staining density of CD68, CD45 and CD56 decreased in diabetes. In the histopathological examination, significant degeneration was detected in the endometrium of diabetic rats. Diabetes could decrease leukocyte proportions in decidua in early pregnancy periods. Therefore immune cell therapies could be administrated in diabetes related problems of pregnancy. PMID- 27179276 TI - Investigation of biochemical composition of adrenal gland tumors by means of FTIR. AB - The application of Fourier transform infrared (FTIR) microspectroscopy for the analysis of biomolecular composition of adrenal gland tumors is described. Samples were taken intraoperatively from three types of adrenal lesions: adrenal adenoma (ACA), adrenal cortical hyperplasia (ACH), both derived from adrenal cortical cells, and pheochromocytoma (Ph) derived from chromaffin cells of the adrenal medulla. The specimens were cryo-sectioned and freeze-dried. Since the investigated lesions originated from different cell types, it was predictable that they might differ in biomolecular composition. The experimental results were used to determine which absorption bands differentiate the analyzed samples the most. The main difference was observed in the lipid functional groups. The experimental results indicated that the level of lipids was higher in both the adenoma and the hyperplasia samples compared to pheochromocytomas. In contrast, the level of proteins was higher in the pheochromocytomas. Furthermore, differences within the range of nucleic acids and carbohydrates were observed in the studied adrenal gland tumor types. PMID- 27179277 TI - Ancient cardiac myxomas - another point of view in the light of tetraspanins. AB - Myxomas are the most common non-invasive but life-threatening cardiac neoplasms due to obstruction of heart chambers and risk of embolism in a manner resembling thromboembolism as well. They can occasionally disseminate via their detached fragments into the bloodstream to seed and grow as secondary still benign tumors. In this study we evaluated morphological and clinical aspects of 14 ancient, degenerated left or right-sided cardiac atrial myxomas with expression of CD9 and CD63, which are found to contribute to platelet activation, aggregation and, as a result, intratumoral thrombosis or fragmentation. The appearance of tumors varied from sessile to polypoid revealing that a higher rate of endocardial thrombosis was associated with sessile compared to polypoid myxomas and left-sided tumors compared to right-sided ones in our study. In the general aspect of ancient calcifications, amorphous calcification with intra-tumor thrombosis was noted more frequently in sessile tumors, while well-formed osseous metaplasia was usually a feature of polypoid tumors. In our material osseous metaplasia did not coexist with massive thrombosis and was found in polypoid, pedunculated myxomas. Most importantly, CD9 overexpression was recorded in every studied myxoma and CD63 gave a weak reaction in myxoma cells. PMID- 27179278 TI - Identification of a molecular defect in a stillborn fetus with perinatal lethal hypophosphatasia using a disease-associated genome sequencing approach. AB - Lethal skeletal disorders represent a heterogeneous and clinically variable group of genetic conditions, usually difficult to diagnose without post-mortem radiological assessment. Here we report on a stillborn patient delivered at 22 weeks of gestation who presented with severe skeletal symptoms comprising limb shortening and intrauterine fractures detected upon prenatal ultrasound and autopsy examination. Since post-mortem X-ray was refused and no phenotypic diagnosis could be attempted, we performed next-generation sequencing (NGS) of 2741 genes associated with all known Mendelian disorders. With this strategy, we were able to demonstrate the diagnosis at a molecular level, which turned out to be perinatal lethal hypophosphatasia (HPP). This severe form of HPP represents an inborn defect of ossification often resulting in stillbirth or postnatal death. The NGS panel revealed compound heterozygous ALPL missense mutations: c.1283G>C(p.Arg428Pro) and c.1363G>A(p.Gly455Ser). Mutations detected in our case, although previously described in other patients, have not been reported to co-occur in a single individual. The diagnosis established in our index using the NGS-based approach could have been successfully reached by standard radiography. Thus, our report points to the importance of X-ray examination in stillborn cases and highlights the emerging role of NGS strategies in the diagnostic process of prenatally manifesting skeletal disorders. PMID- 27179279 TI - Giant cribriform adenocarcinoma of the tongue showing PRKD3 rearrangement. AB - Cribriform adenocarcinoma of the tongue and minor salivary glands (CAMSG) was first described 16 years ago. It typically presents as a mass at the base of the tongue with early spread to lymph nodes, but without potential for distant metastases. In the 2005 World Health Organization Classification of Tumors the entity was classified as a possible variant of polymorphous low-grade adenocarcinoma (PLGA). Since then, more than 40 cases have been described in the English literature. Recently, PRKD1-3 translocation was found in more than 80% of CAMSGs. In some of those cases ARID1A or DDX3X was the translocation partner. We reviewed 183 primary carcinomas of major and minor salivary glands, resected at the Medical University of Gdansk, Poland, in the period 1992-2012, and identified only one case of CAMSG. A giant tumor developed at the base of the tongue in a 76 year-old man. The primary tumor was resected with multiple bilateral cervical lymph node metastases. The patient received radiotherapy but died 10 months after the surgery due to causes not related to the primary cancer. The tumor presented PRKD3 rearrangement as confirmed by FISH. As the tumor is extremely rare (it represented only 0.5% of salivary gland tumors in our series), the controversy on its nosological status is still unresolved. This is the first report in the world literature of a patient who died in the course of CAMSG. PMID- 27179280 TI - Histiocytic necrotising lymphadenitis in mediastinum mimicking thymoma or lymphoma - case presentation and literature review of Kikuchi Fujimoto disease. AB - Kikuchi Fujimoto disease (KFD) as a rare self-limiting lymphadenopathy of short and benign course concerns most frequently the lymph nodes of the neck. The most common symptoms are painfulness of the diseased area, fever and night sweating. The etiology is not well understood, but in the role of pathogenesis viral, autoimmune and genetic factors are taken into account. In the presented case of 37-year-old female it was necessary to exclude diseases such as lymphoma or thymoma because of atypical mediastinal location of Kikuchi Fujimoto disease. After multidisciplinary consultation the lymph node was resected from the mediastinum with videothoracoscopic approach. The diagnosis was difficult for the pathologist because of the large percentage of necrosis of the lymph node but the image was typical for histiocytic necrotizing lymphadenitis. Two cases of patients with KFD limited to the mediastinum have been previously reported in the literature. This article presents the world's first reported case of this disease in the topographic location of the thymus. Furthermore, a review of current literature was made. PMID- 27179281 TI - Symptoms of obstructive defecation syndrome: functional outcome after stapled haemorrhoidectomy. AB - BACKGROUND: Patients with haemorrhoids often present obstructive defecation symptoms. Preoperative they can be classified in three groups: slight, severe and mild symptoms. Aim of this study was to postoperatively evaluate functional outcome in patients who underwent stapled haemorrhoidectomy in mild obstructive defecation syndrome. METHODS: We enrolled 98 patients with mild obstructive defecation symptoms using Wexner score preoperatively (range 8-16) from the 332 consecutive patients treated with stapled haemorrhoidectomy between January 2009 and December 2011. All patients were clinically examined 1 month after surgical treatment and every 6 months with a mean followup of 30 months (range 24-42 months). RESULTS: The 98 patients enrolled included 58 men and 40 women. There were no intraoperative complications. Postoperative complications included four patients. A reduction of Wexner score from a mean preoperative score of 12 to a mean postoperative score of 6 just 6 months after surgery was observed. This difference was statistically significant (p<0.001: Mann-Whitney U test). CONCLUSIONS: Careful clinical evaluation of patients with haemorrhoids and obstructive defecation symptom is required to establish the most appropriate treatment. The results of this study indicated that stapled haemorrhoidectomy can improves the functional symptoms for patients with constipation symptoms of moderate degree. KEY WORDS: Functional outcome, Obstructive defecation symptoms, Stapled haemorrhoidectomy. PMID- 27179282 TI - Intestinal permeability and systemic endotoxemia in patients with acute pancreatitis. AB - BACKGROUND: The bacterial contamination of pancreatic necrosis in acute pancreatitis is supposed to occur through translocation of intestinal bacteria. The aim of this clinical study was to evaluate intestinal mucosa permeability and endotoxemia in patients with acute pancreatitis. METHODS: Sixtythree patients with acute pancreatitis were studied. Classification 42 patients had mild and 21 patients severe pancreatitis. Intestinal permeability was assessed at day 0, 1, 3, 7, 9 and 11 using the lactulose/mannitol differential absorption test. Serial venous blood samples were taken at 0, 30, 60, 90, 120, and 180 minutes, at 12, 24 hours, and at days 3, 7, 9 and 11 for endotoxin measurement RESULTS: Patients with severe pancreatitis had higher intestinal barrier dysfunction compared with patients with mild pancreatitis, the L:M ratio being 0.36 +/- 0.15 and 0.051 +/- 0.013 respectively (p< 0.05). The systemic endotoxin concentration were higher in patients with severe pancreatitis as regards mild pancreatitis (p < 0.05). A significant correlation was observed between the maximum systemic endotoxin concentration and intestinal permeability measured at day 7 in patients with mild (rs = 0.721; p = 0.001) and severe (rs = 0.956; p= 0.001) pancreatitis. CONCLUSION: Gut permeability is increased in patients with acute pancreatitis. Patients with severe pancreatitis may be more exposed to impaired gut barrier function. Moreover the pancreatits (especially severe) can lead to systemic endotoxemia. This agrees with the hypothesis that the splanchnic hypoperfusion, during the pancreatitis, may impair intestinal mucosal barrier function and contribute to the systemic inflammatory response and multiorgan failure. KEY WORDS: Acute pacreatitis, Endotoxemia, Intestinal permeability. PMID- 27179283 TI - Made in Italy for hernia: the Italian history of groin hernia repair. AB - The history of groin hernia surgery is as long as the history of surgery. For many centuries doctors, anatomists and surgeons have been devoted to this pathology, afflicting the mankind throughout its evolution. Since ancient times the Italian contribution has been very important with many representative personalities. Authors, investigators and pioneers are really well represented. Every period (the classic period, the Middle Age, the Renaissance and the post Renaissance) opened new perspectives for a better understanding. During the 18th century, more information about groin anatomy, mainly due to Antonio Scarpa, prepared the Bassini revolution. Edoardo Bassini developed the first modern anatomically based hernia repair. This procedure spread worldwide becoming the most performed surgical technique. After World War II synthetic meshes were introduced and a new era has begun for hernia repair, once again with the support of Italian surgeons, first of all Ermanno Trabucco. But Italian contribution extends also to educational, with the first national school for abdominal wall surgery starting in Rome, and to Italian participation and support in international scientific societies. Authors hereby wish to resume this long history highlighting the "made in Italy" for groin hernia surgery. KEY WORDS: Bassini, Groin hernia, History, Prosthetic repair. PMID- 27179284 TI - Ultrasonography in diagnosis of acute appendicitis. AB - PURPOSE: Acute appendicitis is the most common surgical abdominal emergency. In the early diagnosis of acute appendicitis, the fact that there is no a sign which could be a reliable indicator in most of the patients increases the complications. In this study we aimed to search the relation between Ultrasonography(US) findings in patients with diagnosis of acute appendicitis and postoperative histopathologic investigation on remoced appendix.. MATERIALS AND METHODS: The files of 174 patients who came in our emergency department with lower right abdominal pain were studied retrospectively from January 2013 to May 2014. Of them, 26 patients were excluded, because these patients were not studied with US. US findings and histopathology reports of 148 patients with suspected acute appendicitis and studies preoperatively with abdominal US were enrolled. Greater than 6-mm diameter of the appendix under compression was accepted as positive sign of appandicitis in US. The demographic characteristics of the patients, US findings (acut appendicitis or not) and the pathology results were recorded on the standard proform. RESULTS: Of these 148 patients, 100 were acute appendicitis in preoperative US, and of these 100 patients, 93 histopathologic reports were acute appendicitis, 7 were normal appendices. The sensitivity of US was 75.6 % and specificity was 72 %. Positive predictive value (PPV) was 93 %, negative predictive value (NPV) was 14.6 % and the accuracy of US value was 81.7%. As a result, although US in diagnosis of acute appendicitis is a reliable technique, negative result doesn't mean no acute appendicitis. In order to determine an accurate diagnosis of acute appendicitis clinical and laboratoary findings should be assessed together. KEY WORDS: Abdominal pain, Acute appendicitis, Ultrasonography. PMID- 27179285 TI - Review of a non-epithelial tumour of the small bowel after c-kit revolution. AB - In this article, we reviewed the case of a patient who was object, in 1999, of a published case report of schwannoma of the jejunal wall. Recently, the patient has been referred to our institution for a mass of the stomach identified by upper gastrointestinal endoscopy. The patient underwent a wedge resection of the stomach and a histopathological diagnosis of GIST of the stomach, based on a positive immunohistochemical staining of c-kit and CD34, was made. In consideration of these findings, we performed immunohistochemistry for c-kit and for CD34 on the previous lesion of the jejunal wall, which resulted strongly positive for CD117 and negative for CD34. A new diagnosis of gastrointestinal stromal tumour (GIST) of jejunal wall with moderate risk of progression was made. The lesion was also classified, according to the AJCC Seventh Edition, as a pT3, pN0, Stage II, GIST. This case shows the importance of a reassessment of the diagnosis of mesenchymal neoplasm of the small intestine made before the development of anti-CD117 antibody for a correct prognostic stratification, a better therapeutic management and a close follow-up, if necessary. KEY WORDS: Adjuvant therapy, c-kit, GIST Imatinib. PMID- 27179286 TI - !Cocinar Para Su Salud! Development of a Culturally Based Nutrition Education Curriculum for Hispanic Breast Cancer Survivors Using a Theory-Driven Procedural Model. AB - We developed a theory-based dietary change curriculum for Hispanic breast cancer survivors with the goal of testing the effects of the intervention on change in dietary intake of fruits/vegetables and fat in a randomized, clinical trial. Social cognitive theory and the transtheoretical model were used as theoretical frameworks to structure curriculum components using the Nutrition Education DESIGN Procedure. Formative assessments were conducted to identify facilitators and barriers common to Hispanic women and test the degree of difficulty and appropriateness of program materials. Focus groups provided valuable insight and informed preimplementation modifications to the dietary program. The result was a systematically planned, evidence-based, culturally tailored dietary intervention for Hispanic breast cancer survivors, !Cocinar Para Su Salud! (Cook for Your Health!). The methodology described here may serve as a framework for the development of future dietary interventions among diverse and minority populations. Short- and long-term study results will be reported elsewhere. PMID- 27179287 TI - Predicting Behaviors to Reduce Toxic Chemical Exposures Among New and Expectant Mothers: The Role of Distal Variables Within the Integrative Model of Behavioral Prediction. AB - There is a growing body of evidence linking childhood exposure to environmental toxins and a range of adverse health outcomes, including preterm birth, cognitive deficits, and cancer. Little is known, however, about what drives mothers to engage in health behaviors to reduce such risks. Guided by the integrative model of behavioral prediction, this study surveyed women who were pregnant and/or had children younger than 7 years (N = 819) to identify the factors that determine engagement in behaviors to reduce childhood exposure to toxic chemicals in the environment. Structural equation modeling pertaining to three different environmental toxins-bisphenol A, arsenic, and pesticides-demonstrated that perceived normative pressure was the primary determinant of behavior across all three models. Additionally, we identified two key distal variables-perceived risk and information seeking-that not only increased the model's predictive power but also consistently and positively predicted perceived social norms regarding exposure reduction behaviors. Findings also suggest important differences across these behaviors. Implications for health communication researchers and practitioners developing interventions, communication campaigns, and persuasive messages to promote prenatal and pediatric environmental health are discussed. PMID- 27179288 TI - Activation and Self-Efficacy in a Randomized Trial of a Depression Self-Care Intervention. AB - OBJECTIVES: In a sample of primary care participants with chronic physical conditions and comorbid depressive symptoms: to describe the cross-sectional and longitudinal associations of activation and self-efficacy with demographic, physical and mental health status, health behaviors, depression self-care, health care utilization, and use of self-care tools; and to examine the effects of a depression self-care coaching intervention on these two outcomes. Design/Study Setting. A secondary analysis of activation and self-efficacy data collected as part of a randomized trial to compare the effects of a telephone-based coached depression self-care intervention with a noncoached intervention. Activation (Patient Activation Measure) was measured at baseline and 6 months. Depression self-care self-efficacy was assessed at baseline, at 3 months, and at 6 months. PRINCIPAL FINDINGS: In multivariable cross-sectional analyses (n = 215), activation and/or self-efficacy were associated with language, birthplace, better physical and mental health, individual exercise, specialist visits, and antidepressant nonuse. In longitudinal analyses (n = 158), an increase in activation was associated with increased medication adherence; an increase in self-efficacy was associated with use of cognitive self-care strategies and increases in social and solitary activities. There were significant improvements from baseline to 6 months in activation and self-efficacy scores both among coached and noncoached groups. The self-care coaching intervention did not affect 6-month activation or self-efficacy but was associated with quicker improvement in self-efficacy. CONCLUSIONS: Overall, the results for activation and self efficacy were similar, although self-efficacy correlated more consistently than activation with depression-specific behaviors and was responsive to a depression self-care coaching intervention. PMID- 27179289 TI - Emotional and Behavioral Aspects of Diabetes in American Indians/Alaska Natives. AB - American Indians and Alaska Natives (AI/ANs) bear a disproportionate burden of diabetes and associated long-term complications. Behavioral interventions play a vital role in promoting diabetes medical and psychological outcomes, yet the development of interventions for AI/AN communities has been limited. A systematic review was conducted of studies focused on the psychosocial and behavioral aspects of diagnosed diabetes among AI/ANs. Ovid and PubMed databases and published reference lists were searched for articles published between 1987 and 2014 that related to the psychosocial and behavioral aspects of type 1 or type 2 diabetes in the AI/AN population. Twenty studies were identified that met the inclusion criteria. Nineteen studies were observational and one study was intervention based. Two of the studies used community-based participatory research methodology. Of the 20 studies, 2 discussed cultural influences associated with diabetes self-management and 10 identified the specific tribes that participated in the study. Tribal affiliations among the studies were broad with the number of AI/AN participants in each study ranging from 30 to 23,529 participants. Emotional and behavioral topics found in the literature were adherence ( n = 2), depression ( n = 9), physical activity ( n = 3), psychosocial barriers ( n = 1), social support ( n = 3), and stress ( n = 2). Relatively few studies were identified using AI/AN populations over a 27-year period. This is in stark contrast to what is known about the prevalence and burden that type 1 and type 2 diabetes mellitus place on AI/AN communities. Future research should promote community engagement through the use of community-based participatory research methodologies, seek to further understand and describe the emotional and behavioral context for diabetes self-management in this population, and develop and test innovative interventions to promote the best possible diabetes outcomes. PMID- 27179290 TI - Impact of Goal Setting and Goal Attainment Methods on Asthma Outcomes. AB - Optimal use of goal-setting strategies in self-management efforts with high-risk individuals with asthma is not well understood. This study aimed to describe factors associated with goal attainment in an asthma self-management intervention for African American women with asthma and determine whether goal attainment methods proved beneficial to goal achievement and improved asthma outcomes. Data came from 212 African American women in the intervention arm of a randomized clinical trial evaluating a telephone-based asthma self-management program. Telephone interview data were collected to assess goals and goal attainment methods identified, asthma symptoms, asthma control, and asthma-related quality of life at baseline and 2-year follow-up. Generalized estimating equations were used to assess the long-term impact of goal setting and goal attainment methods on outcomes. The average age of the sample was 42.1 years ( SD = 14.8). Factors associated with goal attainment included higher education ( p < .01) and fewer depressive symptoms ( p < .01). Using a goal attainment method also resulted in more goals being achieved over the course of the intervention (Estimate [ SE] = 1.25 [0.18]; p < .001) when adjusted for clinical and demographic factors. Use of and types of goal attainment methods and goals were not found to significantly affect asthma control, quality of life, or frequency of nighttime asthma symptoms at follow-up. Using a method to achieve goals led to greater goal attainment. Goal attainment alone did not translate into improved asthma outcomes in our study sample. Further studies are warranted to assess the challenges of self management in chronic disease patients with complex health needs and how goal setting and goal attainment methods can be strategically integrated into self management efforts to improve health endpoints. PMID- 27179291 TI - Challenges and Innovations in a Community-Based Participatory Randomized Controlled Trial. AB - Randomized controlled trials (RCTs) are a long-standing and important design for conducting rigorous tests of the effectiveness of health interventions. However, many questions have been raised about the external validity of RCTs, their utility in explicating mechanisms of intervention and participants' intervention experiences, and their feasibility and acceptability. In the current mixed methods study, academic and community partners developed and implemented an RCT to test the effectiveness of a collaboratively developed community-based advocacy, learning, and social support intervention. The goals of the intervention were to address social determinants of health and build trust and connections with other mental health services in order to reduce mental health disparities among Afghan, Great Lakes Region African, and Iraqi refugee adults and to engage and retain refugees in trauma-focused treatment, if needed. Two cohorts completed the intervention between 2013 and 2015. Ninety-three adult refugees were randomly assigned to intervention or control group and completed four research interviews (pre-, mid-, and postintervention, and follow-up). Several challenges to conducting a community-based RCT emerged, including issues related to interviewer intervention to assist participants in the control group, diffusion of intervention resources throughout the small refugee communities, and staff and community concerns about the RCT design and what evidence is meaningful to demonstrate intervention effectiveness. These findings highlight important epistemological, methodological, and ethical challenges that should be considered when conducting community-based RCTs and interpreting results from them. In addition, several innovations were developed to address these challenges, which may be useful for other community-academic partnerships engaged in RCTs. PMID- 27179292 TI - What Does Having Your Pack in Your Pocket Say About You? Characteristics and Attitude Differences of Youth Carrying Tobacco at a Music Festival. AB - The purpose of this study is to understand differences in demographics, frequency of tobacco use, and tobacco-related attitudes between youth/young adults who carry tobacco products and those who do not. Carrying tobacco is hypothesized to affect individuals' smoker identity and thereby their tobacco-related attitudes. Carriers are an influential peer group, often serving as social sources of tobacco for others, setting tobacco-related social norms, and advertising tobacco via the packs they carry. Thus, understanding their characteristics and attitudes can aid in the targeting and tailoring of cessation messaging. In this study, 3,927 attendees ages 13 to 24 years at the Vans Warped Tour were surveyed using iPads and asked to photograph any tobacco products they were currently carrying. Current tobacco users were classified as proven carriers ( n = 363), unproven carriers ( n = 182), or noncarriers ( n = 1,426). Carriers ( N = 545) were older, were more often White, and used tobacco over twice as often as noncarriers. Results indicated carriers and noncarriers differed significantly on most antitobacco attitudes, with carriers feeling less strongly antitobacco. PMID- 27179293 TI - Gleaning structural and functional information from correlations in protein multiple sequence alignments. AB - The availability of vast amounts of protein sequence data facilitates detection of subtle statistical correlations due to imposed structural and functional constraints. Recent breakthroughs using Direct Coupling Analysis (DCA) and related approaches have tapped into correlations believed to be due to compensatory mutations. This has yielded some remarkable results, including substantially improved prediction of protein intra- and inter-domain 3D contacts, of membrane and globular protein structures, of substrate binding sites, and of protein conformational heterogeneity. A complementary approach is Bayesian Partitioning with Pattern Selection (BPPS), which partitions related proteins into hierarchically-arranged subgroups based on correlated residue patterns. These correlated patterns are presumably due to structural and functional constraints associated with evolutionary divergence rather than to compensatory mutations. Hence joint application of DCA- and BPPS-based approaches should help sort out the structural and functional constraints contributing to sequence correlations. PMID- 27179294 TI - The effects of lauromacrogol on thyroid tissue in rabbits. Is this a safe option for the treatment of nodular thyroid disease? AB - AIM: The effects of lauromacrogol as a sclerosing agent were evaluated on rabbit thyroid tissue. MATERIAL AND METHODS: Twelve rabbits were divided into two equal groups. Intra-thyroid injections of 0.1 ml lauromacrogol were administered in the study group and 0.1 ml physiologic serum in the control group. The blood levels of free T3, free T4, TSH, postoperative adhesions and histopathologic differences of the thyroid tissues were evaluated. RESULTS: The values of serum free T3, free T4 and TSH levels did not differ significantly (p>0.05), but the free T3 levels were significantly different in the inter-group analysis (p=0.020). Postoperative macroscopic adhesion scores did not differ significantly (p>0.05). In the histopathologic evaluation, the inflammation and fibrosis scores were significantly higher in the study group (p=0.003). DISCUSSION: In our study, we found two important outcomes. Firstly, tests of thyroid function were not significantly different between the control and study groups. This important finding suggests lauromacrogol can be safely used without the risk of hypothyroidism or hyperthyroidism. Secondly, the Erlich-Hunt Model histopathologic evaluation results revealed that inflammation and fibrosis were significantly increased in the study group. This finding shows lauromacrogol can be effectively used to treat thyroid nodules by means of fibrosis. CONCLUSIONS: Lauromacrogol causes fibrosis in thyroid tissue without significant perithyroidal adhesion formation and functional differences. Treatment of nodular thyroid disease with lauromacrogol may be safe. KEY WORDS: Lauromacrogol, Nodule, Thyroid. PMID- 27179295 TI - Surface-enhanced Raman scattering studies of the reduction of p-nitroaniline catalyzed by a nanonized Ag porous-glass hybrid composite. AB - Nanonized noble metal composites have been known for their excellent catalytic properties. However, the mechanism and intermediates formed on the surfaces of nanocatalysts during catalysis are speculated with mostly insufficient evidence. In this study, to obtain further understanding of the roles of noble metal nanocatalysts in a catalytic reaction, surface-enhanced Raman scattering (SERS) was used to monitor the surfaces of silver (Ag) nanocatalysts. Furthermore, UV Vis spectrometry was used to trace the concentration variations of reactants and products in bulk solutions, thereby correlating the variations of the Ag nanocatalyst surfaces with those in the bulk solutions. Nanonized Ag porous-glass hybrid composites were prepared by reducing naked Ag nanoparticles on porous glass filter plates and were used as catalysts for nitroanilines reduction. The complete process was monitored using SERS and UV-Vis spectrometry simultaneously. The results indicated that the reactant and product molecules adsorbed on the Ag nanocatalysts can reach equilibrium, and the equilibrium is affected by the reaction conditions, including reducing agent concentration, pH of the reaction system, and temperature. In addition, the reduction of reactants in the bulk solutions is also related to the behavior of Ag nanocatalyst surfaces. Furthermore, Ag nanocatalysts can act as electron relays even if their surfaces are occupied by reactants and products. Analyzing the collected SERS and UV-Vis spectra can provide a new insight into Ag nanoparticle catalysis, and the role of Ag nanocatalysts can be further comprehended. PMID- 27179296 TI - The oxidant and laser power-dependent plasmon-driven surface photocatalysis reaction of p-aminothiophenol dimerizing into p,p'-dimercaptoazobenzene on Au nanoparticles. AB - Recently, plasmon-driven surface photocatalysis (PDSPC) reactions have attracted more and more attention by means of surface-enhanced Raman scattering (SERS) because we can in situ monitor the reaction process and determine the final products and their quantities by the real-time SERS spectrum. In this work, self assembly AuNPs with both high catalytic activity and strong SERS effect were used as a bifunctional platform for in situ monitoring of PDSPC reactions. p Aminothiophenol (PATP), a famous model molecule, was selected as a probe molecule and FeCl3 and NaClO were selected as oxidants. In this way, oxidation reaction of PATP dimerizing into p,p'-dimercaptoazobenzene (DMAB) has been investigated by SERS, and the results show that oxidant and laser power can alter the conversion rate of the reaction. This work provides a novel approach for controlling PDSPC reaction rate, which may be useful for understanding the mechanism of PDSPC reactions. PMID- 27179297 TI - Enhanced phosphorus removal from wastewater by growing deep-sea bacterium combined with basic oxygen furnace slag. AB - As one solid waste with potential for phosphorus removal, application of slags in water treatment merits attention. But it was inhibited greatly by alkaline solution (pH>9.5) and cemented clogging generated. To give one solution, phosphorus removal was investigated by combining deep-sea bacterium Alteromonas 522-1 and basic oxygen furnace slag (BOFS). Results showed that by the combination, not only higher phosphorous removal efficiency (>90%) but also neutral solution pH of 7.8-8.0 were achieved at wide ranges of initial solution pH value of 5.0-9.0, phosphorus concentration of 5-30mg/L, salinity of 0.5-3.5%, and temperature of 15-35 degrees C. Moreover, sedimentary property was also improved with lower amount of sludge production and alleviated BOFS cementation with increased porosity and enlarged particle size. These results provided a promising strategy for the phosphorus recovery with slags in large-scale wastewater treatment. PMID- 27179298 TI - Marine microalgae growth and carbon partitioning as a function of nutrient availability. AB - To understand in which way the structural differences of three marine microalgae (Nannochloropsis gaditana, Rhodomonas marina and Isochrysis sp.) affect their carbon partitioning, growth and applicability; a stoichiometric imbalance was imposed by steady carbon and other nutrients variation. Towards high nutrients concentrations/low carbon availability a decrease of 12-51% in C/N microalgae ratio was observed and maximum cell densities were achieved. Moreover, linear correlation between the nutrient input and microalgae protein content were observed. The macromolecular ratios pointed that carbohydrate was the main contributor for the C/N decrement. Although lipid content in R. marina remained constant throughout the experiment, a rise of 37-107% in N. gaditana and Isochrysis sp. was verified. Lipid fractions revealed high percentages of glycolipids in all microalgae (57-73% of total lipids). The present study shows an easy way to understand and modulate microalgae carbon partitioning relying on the field of application. PMID- 27179299 TI - Testing methods to support management decisions in coralligenous and cave environments. A case study at Portofino MPA. AB - Baseline data on the distribution, condition and extent of coralligenous and cave bioconcretions is one of the main requirements of the European Marine Strategy Framework Directive (MSFD) necessary to assess the achievement of a Good Environmental Status (GES) by 2020. In this study the potential of remote sensing and distribution modelling techniques to map, measure descriptors and choose indicators were tested, that could provide standard methods for the assessment of the health status and assist in monitoring activities. It is demonstrated how, by combining different methodologies, it is possible to map the distribution of the bioconcretions with acceptable accuracy and to discriminate the main habitat types and facies. In addition, zonal statistical analysis revealed that fishing activities primarily coincide with areas of high coverage of the bioconcretions. Results demonstrate that the presented methodology is a valuable simple tool to assess several MSFD descriptors and indicators, and could strengthen management efficiency when making informed, ecologically relevant decisions. PMID- 27179300 TI - Synthesis, structure, DFT calculations, electrochemistry, fluorescence, DNA binding and molecular docking aspects of a novel oxime based ligand and its palladium(II) complex. AB - A novel oxime based ligand, phenyl-(pyridine-2-yl-hydrazono)-acetaldehyde oxime (LH), and its palladium(II) complex (1) have been synthesised and spectroscopically characterised. The ligand crystallizes in the monoclinic space group (P21/c). The X-ray crystal structure of the ligand shows that it forms a hydrogen bonded helical network. The ligand has been characterised by C, H and N microanalyses, (1)H and (13)C NMR, ESI-MS, FT-IR and UV-Vis spectral measurements. Geometry optimizations at the level of DFT show that the Pd(II) centre is nested in a square-planar 'N3Cl' coordination chromophore. The diamagnetic palladium complex has been characterised by C, H and N microanalyses, FAB-MS, FT-IR, UV-Vis spectra and molar electrical conductivity measurements. The observed electronic spectrum of 1 correlates with our theoretical findings as evaluated through TD-DFT. 1 displays quasi-reversible Pd(II)/Pd(III) and Pd(III)/Pd(IV) redox couples in its CV in acetonitrile. 1 is nine-fold more emissive with respect to the binding ligand. Biophysical studies have been carried out to show the DNA binding aspects of both the ligand and complex. The binding constants for the ligand and complex were found to be 3.93*10(4) and 1.38*10(3)M(-1) respectively. To have an insight into the mode of binding of LH and 1 with CT DNA a hydrodynamic study was also undertaken. The mode of binding has also been substantiated through molecular docking. A promising groove binding efficacy has been revealed for the ligand. PMID- 27179301 TI - Angularly-selective transmission imaging in a scanning electron microscope. AB - This work presents recent advances in transmission scanning electron microscopy (t-SEM) imaging control capabilities. A modular aperture system and a cantilever style sample holder that enable comprehensive angular selectivity of forward scattered electrons are described. When combined with a commercially available solid-state transmission detector having only basic bright-field and dark-field imaging capabilities, the advances described here enable numerous transmission imaging modes. Several examples are provided that demonstrate how contrast arising from diffraction to mass-thickness can be obtained. Unanticipated image contrast at some imaging conditions is also observed and addressed. PMID- 27179302 TI - From classic ethology to modern neuroethology: overcoming the three biases in social behavior research. AB - A typical current study investigating the neurobiology of animal behavior is likely restricted to male subjects, of standard inbred mouse strains, tested in simple behavioral assays under laboratory conditions. This approach enables the use of advanced molecular tools, alongside standardization and reproducibility, and has led to tremendous discoveries. However, the cost is a loss of genetic and phenotypic diversity and a divergence from ethologically-relevant behaviors. Here we review the pros and cons in behavioral neuroscience studies of the new era, focusing on reproductive behaviors in rodents. Recent advances in molecular technology and behavioral phenotyping in semi-natural conditions, together with an awareness of the critical need to study both sexes, may provide new insights into the neural mechanisms underlying social behaviors. PMID- 27179303 TI - Time trends of polybrominated diphenyl ethers in East China Seas: Response to the booming of PBDE pollution industry in China. AB - The East China Seas (ECSs) are the receptors of the land-based persistent organic pollutants (POPs), such as polybrominated diphenyl ethers (PBDEs) mainly from China through atmospheric deposition driven by the East Asian winter monsoon and fluvial discharge (e.g., Yangtze River and Yellow River), making the offshore sediments to be a good proxy to reconstruct history of those pollutants in China. In this work, four well-placed sediment cores were extracted from the mud areas in the ECSs, and the (210)Pb-dated cores were analyzed to yield historical concentration profiles of PBDEs in the area. The results showed that there was a persistent increase from 1970s and almost no clear sign in the decline of PBDEs until recently in China. More importantly, there was a faster increase of PBDEs from 1990s in China; while this period was just shown as gradually leveling off or even declining trends in developed countries. The persistently increasing trend of PBDEs in China since 1990s could be largely due to the booming of the manufacturing industry and unexpectedly transfer of PBDE pollution from developed countries to China. Besides, the relative high concentrations and fluxes of PBDEs in the core from coastal ECS located near a well-known electrical/electronic waste (e-waste) recycling area suggests an important contribution of PBDE emissions from recycling centers of e-waste in China. Although efforts in environmental monitoring of PBDE contamination have been substantially increased over the last decade, China is still lagging behind in terms of nationwide regulation of PBDE usage and treatment of disposal PBDE-containing products. PMID- 27179304 TI - Oxymatrine attenuates CCl4-induced hepatic fibrosis via modulation of TLR4 dependent inflammatory and TGF-beta1 signaling pathways. AB - Oxymatrine (OMT) is able to effectively protect against hepatic fibrosis because of its anti-inflammatory property, while the underlying mechanism remains incompletely understood. In this study, forty rats were randomly divided into five groups: control group, model group (carbon tetrachloride, CCl4) and three OMT treatment groups (30, 60, 120mg/kg). After CCl4 alone, the fibrosis score was 20.2+/-0.8, and the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hydroxyproline content, and collagen I expression was elevated, but OMT blunted these parameters. Treatment with OMT prevented CCl4 induced increases in expression of pro-inflammatory and pro-fibrotic cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha, meanwhile OMT promoted the expression of anti-inflammatory and anti-fibrotic factors such as interleukin (IL)-10 and bone morphogenetic protein and activin membrane-bound inhibitor (Bambi). Moreover, lipopolysaccharides (LPS) and high mobility group box-1 (HMGB1), which activates Toll-like receptor 4 (TLR4) and modulate hepatic fibrogenesis through hepatic stellate cells (HSCs) or Kupffer cells, were significantly decreased by OMT treatment. These results were further supported by in vitro data. First, OMT suppressed the expression of TLR4 and its downstream pro-inflammatory cytokines, lowered the level of HMGB1, TGF-beta1 in macrophages. Then, OMT promoted Bambi expression and thereby inhibited activation of HSCs mediated by transforming growth factor (TGF)-beta1. In conclusion, this study showed that OMT could effectively attenuate the CCl4-induced hepatic fibrosis, and this effect may be due to modulation of TLR4-dependent inflammatory and TGF beta1 signaling pathways. PMID- 27179305 TI - Matrine ameliorates spontaneously developed colitis in interleukin-10-deficient mice. AB - Interleukin-10 (IL-10)-deficient mice spontaneously develop T cell-mediated colitis. Previous reports have shown that Matrine may reduce the symptoms of acute colitis induced by trinitrobenzene sulfonic acid (TNBS). However, whether Matrine impacts chronic colitis remains unknown. In this study, we investigated whether Matrine could limit the symptoms of spontaneously developed colitis and its potential molecular mechanisms. IL-10 deficient mice were given Matrine or a PBS control by oral gavage daily for 4weeks and were euthanized at week 2 or week 4. We measured body weight, colon length and weight, and histological scores. We also evaluated the spontaneous secretion of IL-12/23p40, IFN-gamma and IL-17 in colon explant cultures as well as IFN-gamma and IL-17 secretion in unseparated mesenteric lymph node (MLN) cells, and assessed IFN-gamma, IL-17, IL-1beta and IL 6 mRNA expression in colon tissue. In addition, we analyzed the proportions of CD4-positive and CD8-positive cells in unseparated MLN cells. Our results show that Matrine-treated mice exhibited better body weight recovery than controls and that histological scores and spontaneously secreted IL-12/23p40, IFN-gamma and IL 17 in colon tissue were significantly decreased in treated mice compared with controls. The proportion of CD4-positive cells of MLNs in treated mice was significantly smaller than that in controls at week 4. Both cytokine production and mRNA expression of IFN-gamma and IL-17 were significantly reduced in treated mice compared with controls. Taken together, our results indicate that Matrine may ameliorate spontaneously developed chronic colitis and could be considered as a therapeutic alternative for chronic colitis. PMID- 27179307 TI - Microstructures, mechanical properties and corrosion resistances of extruded Mg Zn-Ca-xCe/La alloys. AB - Magnesium alloys are considered as good candidates for biomedical applications, the influence of Ce/La microalloying on the microstructure, mechanical property and corrosion performance of extruded Mg-5.3Zn-0.6Ca (wt%) alloy has been investigated in the current study. After Ce/La addition, the conventional Ca2Mg6Zn3 phases are gradually replaced by new Mg-Zn-Ce/La-(Ca) phases (T1'), which can effectively divide the Ca2Mg6Zn3 phase. The Ca2Mg6Zn3/T1' structure in Mg-Zn-Ca-0.5Ce/La alloy is favorably broken into small particles during the extrusion, resulting in an obvious refinement of secondary phase. The dynamic recrystallized grain size is dramatically decreased after 0.5Ce/La addition, and the tensile yield strength is improved, while further addition reverses the effect, due to the grain coarsening. However, the corrosion resistance of extruded Mg-Zn-Ca alloy deteriorates after Ce/La addition, because the diameter of secondary phase particle is remarkably decreased, which increases the amount of cathodic sites and accelerates the galvanic corrosion process. PMID- 27179306 TI - Tetrandrine regulates hepatic stellate cell activation via TAK1 and NF-kappaB signaling. AB - We investigated the anti-fibrotic mechanism of tetrandrine, a bisbenzylisoquinoline alkaloid from the Chinese herb, Stephania tetrandra, on the immortalized HSC-T6 rat hepatic stellate cell line. Tetrandrine (0.39-50MUM) dose and time-dependently inhibited HSC-T6 cell viability within 24h and exhibited almost no cytotoxicity at concentrations lower than 6.25MUM in the presence of tumor necrosis factor-alpha (TNF-alpha). At a much high concentration (50MUM), tetrandrine caused fatal cytotoxity in both HSCs and hepatocytes. TNF-alpha time dependently increased alpha-smooth muscle actin (alpha-SMA) expression, while a lower concentration of tetrandrine (6.25MUM) prior to TNF-alpha treatment reduced the expression of alpha-SMA and TNFR-1-associated death domain (TRADD). TNF-alpha treatment induced TGF-beta-activated kinase-1 (TAK1) and c-Jun N-terminal kinase (JNK) phosphorylation, which were attenuated by tetrandrine. Furthermore, TNF alpha treatment activated nuclear factor-kappaB (NF-kappaB) nuclear translocation and IkappaB-alpha degradation. Tetrandrine treatment prior to TNF-alpha reduced nuclear phosphorylated and total NF-kappaB p65, while the cytosolic IkappaB-alpha and NF-kappaB p65 levels significantly increased. In addition, treatment with only tetrandrine induced the cleavage of caspase-3 and PARP within a range of higher concentrations. Tetrandrine-induced apoptosis was confirmed by the TUNEL assay and flow-cytometric analysis. Treatment with only tetrandrine markedly reduced alpha-SMA expression, except for at lower concentrations of tetrandrine. A higher concentration of tetrandrine (25MUM) induced a significant increase in JNK and extracellular signal-regulated kinase (ERK) phosphorylation, NF-kappaB nuclear translocation and IkappaB-alpha degradation. In conclusion, the anti fibrogenic effects of tetrandrine on HSCs involved a dosage-dependent signaling pathway, based on the tetrandrine concentration, by regulating TAK1, JNK and NF kappaB. The present data provides strong evidence for the anti-fibrotic dosage dependent signaling pathway of tetrandrine. PMID- 27179308 TI - Perceived quality in Day Surgery Units Proposal of an enquiry postoperative questionnaire. AB - INTRODUCTION: Assessing patient satisfaction could be particularly useful in Day Surgery Units, as it helps maintaining and increasing medical care demand. Moreover, it provides feedback that turns out useful for improving quality in departments, and for assessing competence and skill of the whole staff. Background and aim - The purpose of this study was to evaluate the quality perceived in a day surgery unit through a questionnaire, covering the 10 main aspects of the care pathway. MATERIALS AND METHODS: The results of a questionnaire filled by patients undergoing Day Surgery between January 2007 and December 2012 were retrospectively reviewed. Patients undergoing surgery between 2007 and 2009 filled up the questionnaire at the time of the discharge, whereas those operated on between 2009 and 2012 filled up the same questionnaire 30 days after discharge. RESULTS: The results were good in terms of number of returned questionnaires, underlining its comprehensibility and suitability to be filled out. The questionnaires' scores were good in both groups, although quality perceived by the group that completed it in 30 days after surgery were lightly better than the other group's. CONCLUSIONS: The advantages of the questionnaire consisted of an overall improvement of the quality of care, whereas limitations consisted of the difficulty in setting up the questionnaire accurately, interpreting patients' answers correctly, and dispensing the questionnaire in a timely fashion, in order to evaluate the quality perceived by the patients without any bias related to delay, pain and anxiety. KEY WORDS: Day Surgery, Nursing, Questionnaire, Quality. PMID- 27179309 TI - Language and memory for object location. AB - In three experiments, we investigated the influence of two types of language on memory for object location: demonstratives (this, that) and possessives (my, your). Participants first read instructions containing demonstratives/possessives to place objects at different locations, and then had to recall those object locations (following object removal). Experiments 1 and 2 tested contrasting predictions of two possible accounts of language on object location memory: the Expectation Model (Coventry, Griffiths, & Hamilton, 2014) and the congruence account (Bonfiglioli, Finocchiaro, Gesierich, Rositani, & Vescovi, 2009). In Experiment 3, the role of attention allocation as a possible mechanism was investigated. Results across all three experiments show striking effects of language on object location memory, with the pattern of data supporting the Expectation Model. In this model, the expected location cued by language and the actual location are concatenated leading to (mis)memory for object location, consistent with models of predictive coding (Bar, 2009; Friston, 2003). PMID- 27179310 TI - Platelet reactivity in patients receiving a maintenance dose of P2Y12-ADP receptor antagonists undergoing elective percutaneous coronary intervention. AB - BACKGROUND: P2Y12-ADP receptor blockade during percutaneous coronary intervention (PCI) is critical to prevent thrombotic events. In patients under chronic P2Y12 blockers, the use of additional loading dose (LD) before an elective PCI is debated. We aimed to investigate the rate of high on-treatment platelet reactivity (HTPR) in patients undergoing elective PCI during chronic clopidogrel or ticagrelor therapy. METHODS AND RESULTS: We performed a sub-group analysis of a randomized trial comparing ticagrelor and clopidogrel in acute coronary syndrome (ACS) patients undergoing PCI. Multi-vessel disease patients requiring a staged PCI one month after the ACS were included. The VASP (vasodilatatory phosphoprotein) index, which is a specific and reproducible platelet assay to measure P2Y12-ADP receptor activity, was used to assess the biological efficacy of the maintenance dose (MD) of ticagrelor and clopidogrel before PCI. Forty-one patients in each group of randomization required a staged PCI. They were similar regarding the baseline demographic, clinical and angiographic characteristics. The mean VASP index in the ticagrelor group was 20.7+/-8.8% compared to 51.8+/ 17% in the clopidogrel group (p<0.001) before PCI. No patients had a VASP index >=50% in the ticagrelor group compared to 56% in the clopidogrel group (p<0.001). Following PCI the rate of peri-procedural MI was higher in the clopidogrel group (p=0.02). CONCLUSIONS: Unlike clopidogrel MD, ticagrelor MD achieves an optimal PR inhibition in all patients during a staged PCI. PMID- 27179311 TI - CSF and plasma adipokines after tonic-clonic seizures. AB - PURPOSE: Adipokines, especially leptin and adiponectin, have gained increasing importance in pathophysiology of various neurological diseases including epilepsy. There are experimental data suggesting a role for leptin in the genesis of seizures and neuroprotection related to seizures. However there are no clinical studies on the effects of epileptic seizures on adipokines. METHODS: We measured cerebrospinal fluid (CSF) and plasma levels of leptin, adiponectin and adipsin after provoked or unprovoked primary or secondarily generalized tonic clonic seizures in 13 female patients and seven controls. The samples were taken within 24h after the seizure onset. RESULTS: Leptin plasma levels correlated negatively with the time to sample withdrawal, i.e. the longer the time interval between the seizure and the sample the lower the leptin levels in the patients. Interestingly, plasma adiponectin levels were significantly increased after the seizure episode. CONCLUSION: This study provides further evidence that there are seizure-induced acute changes in adipokine metabolism. Leptin concentrations seem to decrease during the first 24h after the seizure whereas adiponectin levels increase. The meaning of this response is far from clear, but it might be an endogenous attempt to prevent harmful effects of epileptic seizures in the central nervous system. PMID- 27179312 TI - Amphetamine alters neural response to sucrose in healthy women. AB - Amphetamine, likely via action on the brain's dopaminergic systems, induces anorectic eating behavior and blunts dopaminergic midbrain activation to rewards. Past work has hypothesized that this blunted reward responsivity is a result of increasing tonic over phasic DA activity. We sought to extend past findings to sweet taste during fMRI following single-blind administration of dextroamphetamine and placebo in 11 healthy women. We hypothesized that neural response in both limbic and cognitive sweet taste circuits would mirror past work with monetary rewards by effectively blunting sweet taste reward, and 'equalizing' it's rewarding taste with receipt of water. Behavioral results showed that amphetamine reduced self-reported hunger (supporting the existence of amphetamine anorexia) and increased self-report euphoria. In addition, region of Interest analysis revealed significant treatment by taste interactions in the middle insula and dorsal anterior cingulate confirming the 'equalizing' hypothesis in the cingulate, but unlike monetary reinforcers, the insula actually evinced enhanced separation between tastes on the amphetamine day. These results suggest a divergence from prior research using monetary reinforcers when extended to primary reinforcers, and may hint that altering dopaminergic signaling in the insula and anterior cingulate may be a target for pharmacological manipulation of appetite, and the treatment of obesity. PMID- 27179313 TI - Reproducibility of hippocampal atrophy rates measured with manual, FreeSurfer, AdaBoost, FSL/FIRST and the MAPS-HBSI methods in Alzheimer's disease. AB - The purpose of this study is to assess the reproducibility of hippocampal atrophy rate measurements of commonly used fully-automated algorithms in Alzheimer disease (AD). The reproducibility of hippocampal atrophy rate for FSL/FIRST, AdaBoost, FreeSurfer, MAPS independently and MAPS combined with the boundary shift integral (MAPS-HBSI) were calculated. Back-to-back (BTB) 3D T1-weighted MPRAGE MRI from the Alzheimer's Disease Neuroimaging Initiative (ADNI1) study at baseline and year one were used. Analysis on 3 groups of subjects was performed - 562 subjects at 1.5T, a 75 subject group that also had manual segmentation and 111 subjects at 3T. A simple and novel statistical test based on the binomial distribution was used that handled outlying data points robustly. Median hippocampal atrophy rates were -1.1%/year for healthy controls, -3.0%/year for mildly cognitively impaired and -5.1%/year for AD subjects. The best reproducibility was observed for MAPS-HBSI (1.3%), while the other methods tested had reproducibilities at least 50% higher at 1.5T and 3T which was statistically significant. For a clinical trial, MAPS-HBSI should require less than half the subjects of the other methods tested. All methods had good accuracy versus manual segmentation. The MAPS-HBSI method has substantially better reproducibility than the other methods considered. PMID- 27179314 TI - Greater hippocampal volume is associated with PTSD treatment response. AB - Previous research associates smaller hippocampal volume with posttraumatic stress disorder (PTSD). It is unclear, however, whether treatment affects hippocampal volume or vice versa. Seventy-six subjects, 40 PTSD patients and 36 matched trauma-exposed healthy resilient controls, underwent clinical assessments and magnetic resonance imaging (MRI) at baseline, and 10 weeks later, during which PTSD patients completed ten weeks of Prolonged Exposure (PE) treatment. The resilient controls and treatment responders (n=23) had greater baseline hippocampal volume than treatment non-responders (n=17) (p=0.012 and p=0.050, respectively), perhaps due to more robust fear-extinction capacity in both the initial phase after exposure to trauma and during treatment. PMID- 27179315 TI - Pallidum and lateral ventricle volume enlargement in autism spectrum disorder. AB - Studies on structural brain abnormalities in individuals with autism spectrum disorders (ASD) have been of limited size and many findings have not been replicated. In the largest ASD brain morphology study to date, we compared subcortical, total brain (TBV), and intracranial (ICV) volumes between 472 subjects with DSM-IV ASD diagnoses and 538 healthy volunteers (age range: 6-64 years), obtained from high-resolution structural brain scans provided by the Autism Brain Imaging Data Exchange (ABIDE). Compared to healthy volunteers, we found significantly larger pallidum (Cohen's d=0.15) and lateral ventricle volumes (Cohen's d=0.18) in ASD. These enlargements were independent of total brain volume and IQ, passed FDR correction for multiple comparisons, and were observed in overall, male-only, and medication-free subjects. In addition, intracranial, hippocampal, and caudate volumes were enlarged in ASD at a nominal statistical threshold of p<0.05. This study provides the first robust evidence for pallidum enlargement in ASD independent from TBV and encourages further study of the functional role of the pallidum in individuals with autism spectrum disorder. PMID- 27179316 TI - Iron biofortification of wheat grains through integrated use of organic and chemical fertilizers in pH affected calcareous soil. AB - Incidence of iron (Fe) deficiency in human populations is an emerging global challenge. This study was conducted to evaluate the potential of iron sulphate combined with biochar and poultry manure for Fe biofortification of wheat grains in pH affected calcareous soil. In first two incubation studies, rates of sulfur (S) and Fe combined with various organic amendments for lowering pH and Fe availability in calcareous soil were optimized. In pot experiment, best rate of Fe along with biochar (BC) and poultry manure (PM) was evaluated for Fe biofortification of wheat in normal and S treated low pH calcareous soil. Fe applied with BC provided fair increase in root-shoot biomass and photosynthesis up to 79, 53 and 67%, respectively in S treated low pH soil than control. Grain Fe and ferritin concentration was increased up to 1.4 and 1.2 fold, respectively while phytate and polyphenol was decreased 35 and 44%, respectively than control in treatment where Fe was applied with BC and S. In conclusion, combined use of Fe and BC could be an effective approach to improve growth and grain Fe biofortification of wheat in pH affected calcareous soil. PMID- 27179317 TI - Is synergistic organisation of muscle coordination altered in people with lateral epicondylalgia? A case-control study. AB - BACKGROUND: Lateral epicondylalgia is a common musculoskeletal disorder and is associated with deficits in the motor system including painful grip. This study compared coordination of forearm muscles (muscle synergies) during repeated gripping between individuals with and without lateral epicondylalgia. METHODS: Twelve participants with lateral epicondylalgia and 14 controls performed 15 cyclical repetitions of sub-maximal (20% maximum grip force of asymptomatic arm), pain free dynamic gripping in four arm positions: shoulder neutral with elbow flexed to 90 degrees and shoulder flexed to 90 degrees with elbow extended both with forearm pronated and neutral. Muscle activity was recorded from extensor carpi radialis brevis/longus, extensor digitorum, flexor digitorum superficialis/profundus, and flexor carpi radialis, with intramuscular electrodes. Muscle synergies were extracted using non-negative matrix factorisation. FINDINGS: Analysis of each position and participant, demonstrated that two muscle synergies accounted for >97% of the variance for both groups. Between-group differences were identified after electromyography patterns of the control group were used to reconstruct the patterns of the lateral epicondylalgia group. A greater variance accounted for was identified for the controls than lateral epicondylalgia (p=0.009). This difference might be explained by an additional burst of flexor digitorum superficialis electromyography during grip release in many lateral epicondylalgia participants. INTERPRETATION: These data provide evidence of some differences in synergistic organisation of activation of forearm muscles between individuals with and without lateral epicondylalgia. Due to study design it is not possible to elucidate whether changes in the coordination of muscle activity during gripping are associated with the cause or effect of lateral epicondylalgia. PMID- 27179318 TI - A two-step flocculation process on oil sands tailings treatment using oppositely charged polymer flocculants. AB - Water management and treatment of mineral tailings and oil sands tailings are becoming critical challenges for the sustainable development of natural resources. Polymeric flocculants have been widely employed to facilitate the flocculation and settling of suspended fine solid particles in tailings, resulting in the separation of released water and solid sediments. In this study, a new flocculation process was developed for the treatment of oil sands tailings by using two oppositely charged polymers, i.e. an anionic polyacrylamide and a natural cationic biopolymer, chitosan. The new process was able to not only improve the clarity of supernatant after settling but also achieve a high settling efficiency. Treatment of the oil sands tailings using pure anionic polyacrylamide showed relatively high initial settling rate (ISR) of ~10.3m/h but with poor supernatant clarity (>1000NTU); while the treatment using pure cationic polymer resulted in clear supernatant (turbidity as low as 22NTU) but relatively low ISR of >2m/h. In the new flocculation process, the addition of anionic polyacrylamide to the tailings was followed by a cationic polymer, which showed both a high ISR (~7.7m/h) and a low turbidity (71NTU) of the supernatant. The flocculation mechanism was further investigated via the measurements of floc size, zeta potential and surface forces. The new flocculation process was revealed to include two steps: (1) bridging of fine solids by anionic polyacrylamide, and (2) further aggregation and flocculation mediated by charge neutralisation of the cationic polymer, which significantly eliminated the fine solids in the supernatants as well as increases floc size. Our results provide insights into the basic understanding of the interactions between polymer flocculants and solid particles in tailings treatment, as well as the development of novel tailings treatment technologies. PMID- 27179319 TI - The impact of Great Cormorants on biogenic pollution of land ecosystems: Stable isotope signatures in small mammals. AB - Studying the isotopic composition of the hair of two rodent species trapped in the territories of Great Cormorant colonies, we aimed to show that Great Cormorants transfer biogens from aquatic ecosystems to terrestrial ecosystems, and that these substances reach small mammals through the trophic cascade, thus influencing the nutrient balance in the terrestrial ecosystem. Analysis of delta(13)C and delta(15)N was performed on two dominant species of small mammals, Apodemus flavicollis and Myodes glareolus, inhabiting the territories of the colonies. For both species, the values of delta(13)C and delta(15)N were higher in the animals trapped in the territories of the colonies than those in control territories. In the hair of A. flavicollis and M. glareolus, the highest values of delta(15)N (16.31+/-3.010/00 and 17.86+/-2.760/00, respectively) were determined in those animals trapped in the biggest Great Cormorant colony. delta(15)N values were age dependent, highest in adult A. flavicollis and M. glareolus and lowest in juvenile animals. For delta(13)C values, age-dependent differences were not registered. delta(15)N values in both small mammal species from the biggest Great Cormorant colony show direct dependence on the intensity of influence. Biogenic pollution is at its strongest in the territories of the colonies with nests, significantly diminishing in the ecotones of the colonies and further in the control zones, where the influence of birds is negligible. Thus, Great Cormorant colonies alter ecosystem functioning by enrichment with biogens, with stable isotope values in small mammals significantly higher in the affected territories. PMID- 27179320 TI - Temporal trends in drug use in Adelaide, South Australia by wastewater analysis. AB - Analysis of municipal wastewater for drug metabolites can reveal the scale of drug use within communities. An Australian city with a population of 1.2million inhabitants was assessed for 4 stimulants: cocaine, methamphetamine, 3.4 methylenedioxymethamphetamine (MDMA) and amphetamine; 6 opioids: codeine, morphine, heroin, fentanyl, oxycodone and methadone; 11 new psychoactive substances (NPS); benzylpiperazine (BZP), trifluoromethylphenylpiperazine (TFMPP), methcathinone, methylone, mephedrone, methylenedioxypyrovalerone (MDPV), alpha pyrrolidinopentiophenone (alpha-PVP), paramethoxyamphetamine (PMA), 25C NBOMe, 25B-NBOMe, 25I-NBOMe; and cannabis, for up to four years between December 2011 and December 2015. Temporal trends revealed increasing usage rates of methamphetamine, cocaine, oxycodone, and fentanyl, while decreasing rates of use were observed for MDMA, BZP and methylone. Use of other opioids and cannabis was generally stable across years, while use of new psychoactive substances fluctuated without an apparent direction. Opioids and cannabis were used at a consistent level through the course of the week, while use of stimulants and some NPS increased on the weekend. Seasonal differences in use were observed for MDMA and cannabis (p$_amp_$lt;0.05) where, on average, MDMA use was approximately 90% higher in December than in other months and cannabis use was approximately 45% lower in each February. Residual month-to-month variability measures on trend free data showed NPS use had higher variability than the stimulants and opioids. Frequent wastewater sampling and analysis over prolonged periods has yielded valuable insights into long-term drug use trends, in some instances revealed important within-year trends, and demonstrated the differing patterns of use of drugs on weekends compared to weekdays. PMID- 27179321 TI - Abandoned PbZn mining wastes and their mobility as proxy to toxicity: A review. AB - Lead and zinc (PbZn) mines are a common occurrence worldwide; and while approximately 240 mines are active, the vast majority have been abandoned for decades. Abandoned mining wastes represent a serious environmental hazard, as Pb, Zn and associated metals are continuously released into the environment, threatening the health of humans and affecting ecosystems. Iron sulfide minerals, when present, can form acid mine drainage and increase the toxicity by mobilizing the metals into more bioavailable forms. Remediation of the metal waste is costly and, in the case of abandoned wastes, the responsible party(ies) for the cleanup can be difficult to determine, which makes remediation a complex and lengthy process. In this review, we provide a common ground from a wide variety of investigations about concentrations, chemical associations, and potential mobility of Pb, Zn and cadmium (Cd) near abandoned PbZn mines. Comparing mobility results is a challenging task, as instead of one standard methodology, there are 4-5 different methods reported. Results show that, as a general consensus, the metal content of soils and sediments vary roughly around 1000mg/kg for Zn, 100 for Pb and 10 for Cd, and mobilities of Cd>Zn>Pb. Also, mobility is a function of pH, particle size, and formation of secondary minerals. New and novel remediation techniques continue to be developed in laboratories but have seldom been applied to the field. Remediation at most of the sites has consisted of neutralization (e.g. lime,) for acid mine discharge, and leveling followed by phytostabilization. In the latter, amendments (e.g. biochar, fertilizers) are added to boost the efficiency of the treatment. Any remediation method has to be tested before being implemented as the best treatment is site-specific. Potential treatments are described and compared. PMID- 27179322 TI - Modeled effects of soil acidification on long-term ecological and economic outcomes for managed forests in the Adirondack region (USA). AB - Sugar maple (Acer saccharum) is among the most ecologically and economically important tree species in North America, and its growth and regeneration is often the focus of silvicultural practices in northern hardwood forests. A key stressor for sugar maple (SM) is acid rain, which depletes base cations from poorly buffered forest soils and has been associated with much lower SM vigor, growth, and recruitment. However, the potential interactions between forest management and soil acidification - and their implications for the sustainability of SM and its economic and cultural benefits - have not been investigated. In this study, we simulated the development of 50 extant SM stands in the western Adirondack region of NY (USA) for 100years under different soil chemical conditions and silvicultural prescriptions. We found that interactions between management prescription and soil base saturation will strongly shape the ability to maintain SM in managed forests. Below 12% base saturation, SM did not regenerate sufficiently after harvest and was replaced mainly by red maple (Acer rubrum) and American beech (Fagus grandifolia). Loss of SM on acid-impaired sites was predicted regardless of whether the shelterwood or diameter-limit prescriptions were used. On soils with sufficient base saturation, models predicted that SM will regenerate after harvest and be sustained for future rotations. We then estimated how these different post-harvest outcomes, mediated by acid impairment of forest soils, would affect the potential monetary value of ecosystem services provided by SM forests. Model simulations indicated that a management strategy focused on syrup production - although not feasible across the vast areas where acid impairment has occurred - may generate the greatest economic return. Although pollution from acid rain is declining, its long-term legacy in forest soils will shape future options for sustainable forestry and ecosystem stewardship in the northern hardwood forests of North America. PMID- 27179323 TI - The regulation of ascorbate biosynthesis. AB - We review the regulation of ascorbate (vitamin C) biosynthesis, focusing on the l galactose pathway. We discuss the regulation of ascorbate biosynthesis at the level of gene transcription (both repression and enhancement) and translation (feedback inhibition of translation by ascorbate concentration) and discuss the eight proteins that have been demonstrated to date to affect ascorbate concentration in plant tissues. GDP-galactose phosphorylase (GGP) and GDP-mannose epimerase are critical steps that regulate ascorbate biosynthesis. These and other biosynthetic genes are controlled at the transcriptional level, while GGP is also controlled at the translational level. Ascorbate feedback on enzyme activity has not been observed unequivocally. PMID- 27179324 TI - Escherichia coli out in the cold: Dissemination of human-derived bacteria into the Antarctic microbiome. AB - Discharge of untreated sewage into Antarctic environments presents a risk of introducing non-native microorganisms, but until now, adverse consequences have not been conclusively identified. Here we show that sewage disposal introduces human derived Escherichia coli carrying mobile genetic elements and virulence traits with the potential to affect the diversity and evolution of native Antarctic microbial communities. We compared E. coli recovered from environmental and animal sources in Antarctica to a reference collection of E. coli from humans and non-Antarctic animals. The distribution of phylogenetic groups and frequency of 11 virulence factors amongst the Antarctic isolates were characteristic of E. coli strains more commonly associated with humans. The rapidly emerging E. coli ST131 and ST95 clones were found amongst the Antarctic isolates, and ST95 was the predominant E. coli recovered from Weddell seals. Class 1 integrons were found in 15% of the Antarctic E. coli with 4 of 5 identified gene cassette arrays containing antibiotic resistance genes matching those common in clinical contexts. Disposing untreated sewage into the Antarctic environment does disseminate non-native microorganisms, but the extent of this impact and implications for Antarctic ecosystem health are, as yet, poorly understood. PMID- 27179325 TI - Stereoselective induction by 2,2',3,4',6-pentachlorobiphenyl in adult zebrafish (Danio rerio): Implication of chirality in oxidative stress and bioaccumulation. AB - This study aimed to investigate the oxidative stress process and bioaccumulation the racemic/(-)-/(+)- 2,2',3,4',6-pentachlorobiphenyl were administered to adult zebrafish (Danio rerio) after prolonged exposure of 56-days uptake and 49-days depuration experiments. Stereoselective accumulation was observed in adult samples after racemic exposure as revealed by decreased enantiomer fractions. The two enantiomers of PCB91 accumulated at different rates with logBCFk values close to 3.7, suggesting that they were highly hazardous and persistent pollutants. Exposure to racemic/(-)-/(+)- PCB91 stereoselectively induced oxidative stress owing to changes in reactive oxygen species, malondialdehyde contents, antioxidant enzyme activities and gene expressions in brain and liver tissues. In addition, the stereoselective relationship between bioconcentration and oxidative stress were also presented in this study. Our findings might be helpful for elucidating the environmental risk of the two enantiomers of PCB91 that induce toxicity in aquatic organisms. PMID- 27179326 TI - Presence of trace metals in aquaculture marine ecosystems of the northwestern Mediterranean Sea (Italy). AB - Information regarding chemical pollutant levels in farmed fish and shellfish, along with the risks associated with their consumption is still scarce. This study was designed to assess levels of exposure to 21 trace elements in fish (Dicentrarchus labrax), mussels (Mytilus galloprovincialis) and oysters (Crassostrea gigas) collected from aquaculture marine ecosystems of the northwestern Mediterranean Sea. Metal concentrations showed great variability in the three species; the highest values of the nonessential elements As and Cd were found in oysters while the highest levels of Al, Pb and V were found in mussels. The essential elements Cu, Mn and Zn were highest in oysters, but Fe, Cr, Ni, Se, Co and Mo levels were highest in mussels. Fish had the lowest concentrations for all trace elements, which were at least one order of magnitude lower than in bivalves. The rare earth elements cerium and lanthanum were found at higher levels in mussels than in oysters, but undetectable in fish. The maximum values set by European regulations for Hg, Cd and Pb were never exceeded in the examined samples. However, comparing the estimated human daily intakes (EHDIs) with the suggested tolerable copper and zinc intakes suggested a potential risk for frequent consumers of oysters. Similarly, people who consume high quantities of mussels could be exposed to concentrations of Al that exceed the proposed TWI (tolerable weekly intake). PMID- 27179327 TI - Estimation of anthropogenic heat emissions in urban Taiwan and their spatial patterns. AB - High energy consumption in the urban environment impacts the urban surface energy budget and causes the emission of anthropogenic heat fluxes (AHFs) into the atmosphere. AHFs vary over time and space. Thus, a reliable estimation of AHF is needed for mesoscale meteorological modeling. This study used a statistical regression method to estimate the annual mean gridded AHF with high spatial (1 km) resolution. Compared with current methods for AHF estimation, the statistical regression method is straightforward and can be easily incorporated with meteorological modeling. AHF of the highly populated urban areas in Taiwan were estimated using data from the anthropogenic pollutant emission inventory of CO and NOx for year 2010. Over 40% of the total AHF values in Taiwan main island fell within the range of 10-40 Wm(-2). When the study domain was confined to urban land, the percentage contributions from AHF values were increased, with over 68% of the total AHF values within the range of 10-40 Wm(-2). AHF values > 40 Wm(-2) were more abundant in the Southern region, followed by the Central and Northern regions. An assessment of the heat emissions by the large scale urban consumption of energy (LUCY) model revealed that the mean AHFs are reasonably close to those produced while the maximum AHFs are underestimated. The results obtained evidence the impact of spatial distribution of land use types, particularly population densities, main highways and industries on AHF generation in Taiwan. PMID- 27179328 TI - Metal-free catalysis of persulfate activation and organic-pollutant degradation by nitrogen-doped graphene and aminated graphene. AB - We evaluated three types of functionalized, graphene-based materials for activating persulfate (PS) and removing (i.e., sorption and oxidation) sulfamethoxazole (SMX) as a model emerging contaminant. Although advanced oxidative water treatment requires PS activation, activation requires energy or chemical inputs, and toxic substances are contained in many catalysts. Graphene based materials were examined herein as an alternative to metal-based catalysts. Results show that nitrogen-doped graphene (N-GP) and aminated graphene (NH2-GP) can effectively activate PS. Overall, PS activation by graphene oxide was not observed in this study. N-GP (50 mg L(-1)) can rapidly activate PS (1 mM) to remove >99.9% SMX within 3 h, and NH2-GP (50 mg L(-1)) activated PS (1 mM) can also remove 50% SMX within 10 h. SMX sorption and total removal was greater for N GP, which suggests oxidation was enhanced by increasing proximity to PS activation sites. Increasing pH enhanced the N-GP catalytic ability, and >99.9% SMX removal time decreased from 3 h to 1 h when pH increased from 3 to 9. However, the PS catalytic ability was inhibited at pH 9 for NH2-GP. Increases in ionic strength (100 mM NaCl or Na2SO4) and addition of radical scavengers (500 mM ethanol) both had negligible impacts on SMX removal. With bicarbonate addition (100 mM), while the catalytic ability of N-GP remained unaltered, NH2-GP catalytic ability was inhibited completely. Humic acid (250 mg L(-1)) was partially effective in inhibiting SMX removal in both N-GP and NH2-GP systems. These results have implications for elucidating oxidant catalysis mechanisms, and they quantify the ability of functionalization of graphene with hetero-atom doping to effectively catalyze PS for water treatment of organic pollutants including emerging contaminants. PMID- 27179329 TI - Revealing ecological risks of priority endocrine disrupting chemicals in four marine protected areas in Hong Kong through an integrative approach. AB - Marine Protected Areas (MPAs) in Hong Kong are situated in close proximity to urbanized areas, and inevitably influenced by wastewater discharges and antifouling biocides leached from vessels. Hence, marine organisms inhabiting these MPAs are probably at risk. Here an integrative approach was employed to comprehensively assess ecological risks of eight priority endocrine disrupting chemicals (EDCs) in four MPAs of Hong Kong. We quantified their concentrations in environmental and biota samples collected in different seasons during 2013-2014, while mussels (Septifer virgatus) and semi-permeable membrane devices were deployed to determine the extent of accumulation of the EDCs. Extracts from the environmental samples were subjected to the yeast estrogen screen and a novel human cell-based catechol-O-methyltransferase ELISA to evaluate their estrogenic activities. The results indicated ecological risks of EDCs in the Cape d'Aguilar Marine Reserve. This integrated approach can effectively evaluate ecological risks of EDCs through linking their concentrations to biological effects. PMID- 27179330 TI - Atmospheric occurrence and gas-particle partitioning of PBDEs at industrial, urban and suburban sites of Thessaloniki, northern Greece: Implications for human health. AB - Air samples were collected during the cold and the warm period of the year 2012 and 2013 at three sites in the major Thessaloniki area, northern Greece (urban industrial, urban-traffic and urban-background) in order to evaluate the occurrence, profiles, seasonal variation and gas/particle partitioning of polybrominated diphenyl ethers (PBDEs). The mean total concentrations of particle phase ?12PBDE in the cold season were 28.7, 19.5 and 3.87 pg m(-3) at the industrial, urban-traffic and urban-background site, respectively, dropping slightly in the warm season (23.7, 17.5 and 3.14 pg m(-3)), respectively. The corresponding levels of gas-phase ?12PBDE were 14.4, 7.15 and 4.73 pg m(-3) in the cold season and 21.2, 11.1 and 6.27 pg m(-3) in the warm season, respectively. In all samples, BDE-47 and BDE-99 were the dominant congeners. Absorption of PBDEs in the organic matter of particles appeared to drive their gas/particle partitioning, particularly in the cold season. The estimated average outdoor workday inhalation exposure to ?12PBDE in the cold and the warm period followed the order: industrial site (288 and 299 pg day(-1)) > urban-traffic site (178 and 191 pg day(-1)) > urban-background site (58 and 63 pg day(-1)). The exposures to BDE-47, BDE-99, BDE-153 and ?3PBDE via inhalation, for children outdoor worker and seniors were several orders of magnitude lower than their corresponding oral RfD values. PMID- 27179331 TI - Artificial light at night disrupts sleep in female great tits (Parus major) during the nestling period, and is followed by a sleep rebound. AB - Artificial light at night has been linked to a wide variety of physiological and behavioural consequences in humans and animals. Given that little is known about the impact of light pollution on sleep in wild animals, we tested how experimentally elevated light levels affected sleep behaviour of female songbirds rearing 10 day old chicks. Using a within-subject design, individual sleep behaviour was observed over three consecutive nights in great tits (Parus major), with females sleeping in a natural dark situation on the first and third night, whereas on the second night they were exposed to a light-emitting diode (1.6 lux). Artificial light in the nest box dramatically and significantly affected sleep behaviour, causing females to fall asleep later (95 min; while entry time was unaffected), wake up earlier (74 min) and sleep less (56%). Females spent a greater proportion of the night awake and the frequency of their sleep bouts decreased, while the length of their sleep bouts remained equal. Artificial light also increased begging of chicks at night, which may have contributed to the sleep disruption in females or vice versa. The night following the light treatment, females slept 25% more compared to the first night, which was mainly achieved by increasing the frequency of sleep bouts. Although there was a consistent pattern in how artificial light affected sleep, there was also large among-individual variation in how strongly females were affected. When comparing current results with a similar experiment during winter, our results highlight differences in effects between seasons and underscore the importance of studying light pollution during different seasons. Our study shows that light pollution may have a significant impact on sleep behaviour in free-living animals during the reproductive season, which may provide a potential mechanism by which artificial light affects fitness. PMID- 27179332 TI - Remarkable regression of a giant cell tumor of the cervical spine treated conservatively with denosumab: A case report. AB - INTRODUCTION: Wide resection of giant cell tumors at the cervical spine is sometimes extremely challenging, especially in cases where tumors extend into the nearby tissues, such as vertebral arteries, the spinal cord, or spinal nerve roots. Denosumab, a human monoclonal antibody that binds the receptor activator of nuclear factor kappa-beta ligand, is reported to be effective for decreasing resorption of giant cell tumor of the bone, but the detailed progress of giant cell tumors in the cervical spine extending into the nearby tissues after such treatment has not been reported. PRESENTATION OF CASE: A 41-year-old man presented with neck pain. Computed tomography-guided needle biopsy showed numerous giant cells with a large vesicular nucleus, consistent with a giant cell tumor. Because of the extension of the tumor with involvement of the vertebral artery and surrounding tissues, denosumab (120mg) was administered subcutaneously once per month for 24 months. Six months after denosumab treatment, follow-up computed tomography revealed a dramatic regression and osteosclerosis of the tumor. Two years after starting denosumab treatment, positron emission tomography showed no tumor recurrence. DISCUSSION: Although the tumor was extended with involvement of the surrounding tissues and surgery following denosumab treatment was not performed, at 24 months since initiation of denosumab treatment we confirmed complete regression radiographically. CONCLUSIONS: Denosumab may be used as an adjuvant by which to avoid or reduce the risks and morbidity of surgical treatment in patients with spinal giant cell tumors extending into nearby tissues. PMID- 27179333 TI - Angiosarcoma arising in the non-operated, sclerosing breast after primary irradiation, surviving 6 years post-resection: A case report and review of the Japanese literature. AB - INTRODUCTION: Angiosarcoma consists only 0.04% of all breast malignancies and has a poor prognosis. This is the first reported case of an angiosarcoma arising in the non-operated breast after primary irradiation for occult breast cancer. The patient underwent mastectomy, surviving disease free for 6 years. PRESENTATION OF CASE: A 73-year-old woman with a past history of irradiation of the non-operated left breast complained of skin thickening and crust formation on the left nipple 8 years post-irradiation. Considering the clinical history and radiological studies, recurrent cancer was suspected and biopsy was performed. However, no proof of malignancy was obtained. As clinical symptoms continued to advance, informed consent was obtained and mastectomy was performed. Histological examination of the surgical specimen revealed angiosarcoma. DISCUSSION: In this case, angiosarcoma occurred after radiation on a non-operated breast. Preoperative diagnosis was not achieved even with two cytology specimen and one biopsy. Each showed only fibrosis and inflammatory changes. The background breast tissue inflammation should have been caused by radiation. Marked fibrosis and the rather small number of sarcoma cells in the breast tumor in this case may be why bioptic diagnosis was difficult. Kaplan-Meier analysis of 60 Japanese breast angiosarcoma patients showed significantly better prognosis in patients with a tumor 2cm or smaller. CONCLUSION: Angiosarcoma may occur in the non-operated breast, post irradiation. The potential difficulties of diagnosing angiosarcoma against background fibrosis should be kept in mind. Initial radical surgery currently represents the only effective treatment for improving survival in these patients. PMID- 27179334 TI - Minimally-invasive complete resection of intrathoracic mediastinal lesions with a Linder-Dahan spreadable-blade video mediastinoscope system: A report of two cases. AB - INTRODUCTION: Cervical mediastinoscopy can provide a minimally invasive access to the paratracheobronchial mediastinum within its reachable range, but its operability is substantially limited because of its small operative field, poor visualisation, and one-handed operation. PRESENTATION OF CASES: Patient 1, a 56 year-old woman, presented with a 22*17mm, non-symptomatic, (18)F-fluorodeoxy glucose (FDG)-avid, solid schwannoma originating from the vagus nerve trunk in the right upper paratracheal space. Patient 2, a 55-year-old man, presented with a 55*41mm cystic mass in the left upper paratracheal space that extensively compressed and dislocated the trachea toward the right, which caused dyspnoea and cervicothoracic pain. The masses in both cases were completely resected using a Linder-Dahan spreadable-blade video mediastinoscope. DISCUSSION: The addition of the video system and spreadable blades to the conventional scope combined with a scope-holding device has enabled effective bi-manual preparation and more precise and safer mediastinoscopic procedures than those performed using the conventional one-handed mediastinoscope. Owing to the improved operability, more complex or extended procedures could be performed in wider and more stable operative spaces with better visualisation, although the system has the same minimal invasiveness as that of the conventional mediastinoscope. CONCLUSION: We describe two patients with mediastinal lesions that were effectively resected by using this sophisticated video mediastinoscope system. PMID- 27179336 TI - Eosinophilic cystitis and haematuria: Case report of a rare disease and common presentation. AB - INTRODUCTION: Eosinophilic cystitis is a rare inflammatory condition of the bladder that can cause haematuria. The aetiology is unknown and clinical presentation is difficult to distinguish from other causes of haematuria. Diagnosis is confirmed by biopsy. In this case, a patient with haematuria is diagnosed with eosinohpilic cystitis after presenting to hospital. He was commenced on antibiotics for a presumed urinary tract infection with no resolution of haematuria and symptoms. After diagnosis he was commenced on treatment with resolution of symptoms. CASE PRESENTATION: A 73-year-old male presents with first episode of haematuria. He was initially diagnosed with a urinary tract infection and commenced on antibiotics with no resolution. After further investigations including a cystoscopy and bladder biopsy, he was diagnosed with eosinophilic cystitis. He was treated with steroids improving his symptoms. CONCLUSION: Eosinophilic cystitis is a rare disease of the bladder which is difficult to distinguish from other causes of haematuria, and is often misdiagnosed. Bladder biopsy is necessary for diagnosis. Early diagnosis is important, and it is through a combination of non-operative and operative interventions such as biopsy. Natural history is difficult to predict as it is difficult to determine is a patient will have a benign course with resolution with or without treatment, or result in a chronic course which may result in bladder damage and renal failure. This case highlights the importance of investigating haematuria that is unresponsive to initial empiric treatment such as antibiotics. It is important to refer to a Urologist for further investigation to rule out a sinister cause, but to also obtain a diagnosis, leading to definitive treatment. PMID- 27179335 TI - Right sided spleen laying retro-duodenal: A case report and review of the literature. AB - INTRODUCTION: Unlike left sided accessory spleen that are seen in 10-30% of cases at autopsy, cases of right accessory spleens are extremely rare. This congenital body of healthy splenic tissue simulates tumors from neighboring organs and presents a challenge in formulating a differential diagnosis. PRESENTATION OF CASE: We present the case of a patient whose CT scan of the abdomen showed a large mass, 11*8cm, arising retro-duodenal and lying just anterior to the right kidney. To the best of our knowledge, this is the only case where the accessory spleen was found retro-duodenal, directly anterior to the kidney and completely separate from the supra-renal gland. The chief complaint of the patient was right upper quadrant pain, radiating to the back, and colicky in nature. The patient was diagnosed with duodenal gastro-intestinal stromal tumor and a retro peritoneal sarcoma. The mass was removed via a Kocher's incision and immunohistological examination showed that it was a right sided accessory spleen. The patient's left sided spleen appeared normal. DISCUSSION: Efforts to distinguish an accessory spleen from a retroperitoneal tumor with available scans, percutaneous biopsy or biochemical tests are inconclusive. Differential diagnosis between a retroperitoneal tumor and an accessory spleen can only be made after surgical exploration. CONCLUSION: This case highlights the fact that surgeons should consider the possibility of an accessory spleen when making a differential diagnosis of retroperitoneal tumors. PMID- 27179337 TI - Transient epiphyseal lesion of the femoral head after traumatic hip dislocation: A case report. AB - INTRODUCTION: We experienced a rare case in which magnetic resonance imaging (MRI) showed a transient epiphyseal lesion of the femoral head four months after traumatic hip dislocation. To our knowledge, there have been no previously published reports on the development of such transient lesions after traumatic hip dislocation involving no abnormalities just after dislocation. PRESENTATION OF CASE: We report a 22-year-old man who showed a transient epiphyseal lesion of the femoral head after traumatic hip dislocation. On MRI performed two days after dislocation, no bony injuries were observed around the hip joint. Four months after dislocation, the patient suddenly experienced right hip pain without any new trauma or injury. A low-intensity band convex to the articular surface was apparent above the epiphyseal scar on T1-weighted imaging, and bone marrow edema was observed around the band lesion on short-tau inversion recovery imaging. Following a two-month period of non-surgical conservative therapy, the patient's hip pain resolved and the low-intensity band was no longer observed on follow-up MRI. DISCUSSION: Although the detailed pathogenesis of this transient changes was unclear, we speculate that prolonged rest after traumatic hip dislocation may contribute to bone insufficiency, resulting in an insufficiency fracture of the femoral head. CONCLUSION: This study suggests that transient epiphyseal lesions of the femoral head may occur in patients with a history of traumatic hip dislocation associated with an adapted long-term rest. PMID- 27179339 TI - Efficient conversion of dimethylarsinate into arsenic and its simultaneous adsorption removal over FeCx/N-doped carbon fiber composite in an electro-Fenton process. AB - In this study, a FeCx/N-doped carbon fiber composite (FeCx/NCNFs) was developed via an electrospinning method. According to the characterization results of XRD, TEM and XPS, FeCx (a mixture of Fe7C3 and Fe3C) was either embedded in or attached to the NCNFs. It was used for the first time as a catalyst for dimethylarsinate (DMA) degradation and as an absorbent for inorganic arsenic (As (V)), with degradation and adsorption occurring simultaneously, in an electro Fenton process. The effects of catalyst dosage, initial DMA concentration, solution pH, and applied current on the treatment efficiency and the corresponding H2O2 generation were systematically investigated. The results showed that DMA could be efficiently oxidized into As(V). 96% of DMA was degraded after reaction time of 360 min and the residual As(V) concentration in solution was below the allowable limit of 0.01 mg/L under the optimum treatment conditions. Based on an ESR and radical scavenger experiment, OH was proven to be the sole reactive oxygen species involved in the degradation process of DMA. DMA was oxidized to MMA as the primary oxidation product, which was subsequently oxidized to inorganic arsenic, As (V). TOC was also efficiently removed at the same time. The DMA removal mechanism for simultaneous degradation of dimethylarsinate and adsorption of arsenic over FeCx/NCNFs in the electro-Fenton process was also proposed based on the experimental results. PMID- 27179338 TI - Neurocognitive functioning in individuals with bipolar disorder and their healthy siblings: A preliminary study. AB - BACKGROUND: Cognitive deficits have been consistently reported in individuals with bipolar disorder (BD). The cognitive profile of siblings of individuals with BD is, however, less clearly established possibly due to the heterogeneity of neuropsychological measures used in previous studies. The aim of this exploratory study was to assess the cognitive function of siblings of individuals with BD and compare it with that of their first-degree relatives suffering with BD, and healthy controls (HC) using the Cambridge Neuropsychological Test Automated Battery (CANTAB) - a comprehensive and validated computerized cognitive battery. METHODS: We recruited 23 HC (33.52+/-10.29 years, 8 males), 27 individuals with BD (34.26+/-10.19 years, 9 males, 25 BDI, 1BDII and 1 BD-NOS), and 15 of their biologically related siblings (37.47+/-13.15 years, 4 males). Siblings had no current or lifetime history of mental disorders. Participants performed the CANTAB and completed questionnaires assessing mood and global functioning. Multivariate analyses compared CANTAB measures across the three participant groups. RESULTS: Individuals with BD and their siblings were less accurate in a task of sustained attention (Rapid Visual Processing) when compared to HC. Further, individuals with BD displayed pronounced deficits in affective processing (Affective Go/No-Go) compared to HC. There were no cognitive differences between siblings and individuals with BD. After correcting for current depressive symptoms, these results did not reach statistical significance. CONCLUSIONS: Subthreshold depressive symptoms may be associated with reduced sustained attention in healthy siblings of BD patients. This preliminary result needs to be corroborated by large-scale, longitudinal studies assessing the relationship between cognition and mood in vulnerable individuals. PMID- 27179340 TI - A novel eductor-based MBR for the treatment of domestic wastewater. AB - A novel aeration device has been developed that combines the mechanism of a venturi aerator with the flow multiplier effect of an eductor used for pump driven mixing. The performance of this novel eductor was evaluated in a flat sheet immersed MBR and compared with the same MBR equipped with a conventional diffuser for the treatment of domestic wastewater. The eductor showed a higher rate of oxygen transfer both in clean and wastewater compared to the diffuser. The alpha value with the eductor (0.91) was also found to be more than that of the diffuser (0.75). Higher recirculation rate through the eductor resulted in a higher mixing/turbulance inside the MBR tank and thus alleviated membrane fouling significantly compared to the diffuser. The performance of the MBR in terms of organics removal was also found to be higher with the eductor than the diffuser. The eductor could have significant potential as a combined aerator and mixer in the field of wastewater treatment by MBR. PMID- 27179341 TI - A novel test method to determine the filter material service life of decentralized systems treating runoff from traffic areas. AB - In recent years, there has been a significant increase in the development and application of technical decentralized filter systems for the treatment of runoff from traffic areas. However, there are still many uncertainties regarding the service life and the performance of filter materials that are employed in decentralized treatment systems. These filter media are designed to prevent the transport of pollutants into the environment. A novel pilot-scale test method was developed to determine - within a few days - the service lives and long-term removal efficiencies for dissolved heavy metals in stormwater treatment systems. The proposed method consists of several steps including preloading the filter media in a pilot-scale model with copper and zinc by a load of n-1 years of the estimated service life (n). Subsequently, three representative rain events are simulated to evaluate the long-term performance by dissolved copper and zinc during the last year of application. The presented results, which verified the applicability of this method, were obtained for three filter channel systems and six filter shaft systems. The performance of the evaluated systems varied largely for both tested heavy metals and during all three simulated rain events. A validation of the pilot-scale assessment method with field measurements was also performed for two systems. Findings of this study suggest that this novel method does provide a standardized and accurate estimation of service intervals of decentralized treatment systems employing various filter materials. The method also provides regulatory authorities, designers, and operators with an objective basis for performance assessment and supports stormwater managers to make decisions for the installation of such decentralized treatment systems. PMID- 27179342 TI - The development of environmental visions and strategies at the municipal level: Case studies from the county of Ostergotland in Sweden. AB - Sweden faces a number of environmental challenges. Municipalities can play an important role in managing these challenges. Using interviews with 13 municipalities in the county of Ostergotland, the manner via which environmental visions and strategies were developed and implemented, and the challenges were explored. Differences were found in the effective development and implementation of both environmental visions and strategies due to a range of factors including the range and level of involvement of different stakeholders, variation in what constituted an environmental strategy, and the time horizons employed for the visions. Suggestions for how best to overcome the barriers are outlined. PMID- 27179343 TI - Visualizing ensembles in structural biology. AB - Displaying a single representative conformation of a biopolymer rather than an ensemble of states mistakenly conveys a static nature rather than the actual dynamic personality of biopolymers. However, there are few apparent options due to the fixed nature of print media. Here we suggest a standardized methodology for visually indicating the distribution width, standard deviation and uncertainty of ensembles of states with little loss of the visual simplicity of displaying a single representative conformation. Of particular note is that the visualization method employed clearly distinguishes between isotropic and anisotropic motion of polymer subunits. We also apply this method to ligand binding, suggesting a way to indicate the expected error in many high throughput docking programs when visualizing the structural spread of the output. We provide several examples in the context of nucleic acids and proteins with particular insights gained via this method. Such examples include investigating a therapeutic polymer of FdUMP (5-fluoro-2-deoxyuridine-5-O-monophosphate) - a topoisomerase-1 (Top1), apoptosis-inducing poison - and nucleotide-binding proteins responsible for ATP hydrolysis from Bacillus subtilis. We also discuss how these methods can be extended to any macromolecular data set with an underlying distribution, including experimental data such as NMR structures. PMID- 27179344 TI - Eating- and weight-related factors associated with depressive symptoms in emerging adulthood. AB - Research suggests that eating- and weight-related disturbances (EWRDs) are key factors associated with depressive symptoms. However, it is unclear how EWRDs, and to a greater extent body appreciation, are associated with depressive symptoms among emerging adults. This study investigated the association between EWRDs, body appreciation, and depressive symptoms among emerging adults. Female (n=473) and male (n=135) emerging adults completed measures of restrained eating, emotional eating, external eating, drive for muscularity, body appreciation, and depressive symptoms. Hierarchical multiple regression analyses, performed separately for women and men, found that restrained eating was significantly related to depressive symptoms among both genders, whereas emotional and external eating were significantly associated with depressive symptoms in women only. Body appreciation was negatively associated with depressive symptoms in both genders. The findings highlight the need for clinicians to assess for EWRDs and promote positive body appreciation among emerging adults. PMID- 27179345 TI - Human papillomavirus promotes Epstein-Barr virus maintenance and lytic reactivation in immortalized oral keratinocytes. AB - Epstein-Barr virus and human papillomaviruses are human tumor viruses that infect and replicate in upper aerodigestive tract epithelia and cause head and neck cancers. The productive phases of both viruses are tied to stratified epithelia highlighting the possibility that these viruses may affect each other's life cycles. Our lab has established an in vitro model system to test the effects of EBV and HPV co-infection in stratified squamous oral epithelial cells. Our results indicate that HPV increases maintenance of the EBV genome in the co infected cells and promotes lytic reactivation of EBV in upper layers of stratified epithelium. Expression of the HPV oncogenes E6 and E7 were found to be necessary and sufficient to account for HPV-mediated lytic reactivation of EBV. Our findings indicate that HPV increases the capacity of epithelial cells to support the EBV life cycle, which could in turn increase EBV-mediated pathogenesis in the oral cavity. PMID- 27179347 TI - Inhibition of hepatitis B virus replication by a dNTPase-dependent function of the host restriction factor SAMHD1. AB - SAMHD1 is a cellular protein that possesses dNTPase activity and inhibits retroviruses and DNA viruses through the depletion of cellular dNTPs. However, recent evidence suggests the existence of alternative or additional mechanisms that involve novel nuclease activities. Hepatitis B virus is a DNA virus but resembles retroviruses in that its DNA genome is synthesized via reverse transcription of an RNA transcript. SAMHD1 was shown to inhibit the expression and replication of a transfected HBV DNA. We further investigated the antiviral mechanisms in a newly developed infection assay. Our data indicated that SAMHD1 exerts a profound antiviral effect. In addition, unlike previous findings, our results demonstrate the essential role of SAMHD1 dNTPase. SAMHD1 did not affect virion-derived cccDNA and gene expression but specifically inhibited viral DNA synthesis. These results indicate that SAMHD1 inhibits HBV replication at the reverse transcription step, most likely through the depletion of cellular dNTPs. PMID- 27179346 TI - Lack of strong anti-viral immune gene stimulation in Torque Teno Sus Virus1 infected macrophage cells. AB - While recent findings suggest that swine TTVs (TTSuVs) can act as primary or co infecting pathogens, very little is known about viral immunity. To determine whether TTSuVs downregulate key host immune responses to facilitate their own survival, a swine macrophage cell line, 3D4/31, was used to over-express recombinant TTSuV1 viral particles or the ORF3 protein. Immune gene expression profiles were assessed by a quantitative PCR panel consisting of 22 immune genes, in cell samples collected at 6, 12, 24 and 48h post-transfection. Despite the upregulation of IFN-beta and TLR9, interferon stimulated innate genes and pro inflammatory genes were not upregulated in virally infected cells. The adaptive immune genes, IL-4 and IL-13, were significantly downregulated at 6h post transfection. The ORF3 protein did not appear do not have a major immuno suppressive effect, nor did it stimulate anti-viral immunity. Data from this study warrants further investigation into the mechanisms of TTV related immuno pathogenesis. PMID- 27179348 TI - A review of primary care interventions to improve health outcomes in adult survivors of adverse childhood experiences. AB - Research has consistently demonstrated a link between the experience of adverse childhood experiences (ACEs) and adult health conditions, including mental and physical health problems. While a focus on the prevention or mitigation of adversity in childhood is an important direction of many programs, many individuals do not access support services until adulthood, when health problems may be fairly engrained. It is not clear which interventions have the strongest evidence base to support the many adults who present to services with a history of ACEs. The current review examines the evidence base for psychosocial interventions for adults with a history of ACEs. The review focuses on interventions that may be provided in primary care, as that is the setting where most patients will first present and are most likely to receive treatment. A systematic review of the literature was completed using PsycInfo and PubMed databases, with 99 studies identified that met inclusion and exclusion criteria. These studies evaluated a range of interventions with varying levels of supportive evidence. Overall, cognitive-behavioral therapies (CBT) have the most evidence for improving health problems - in particular, improving mental health and reducing health-risk behaviors - in adults with a history of ACEs. Expressive writing and mindfulness-based therapies also show promise, whereas other treatments have less supportive evidence. Limitations of the current literature base are discussed and research directions for the field are provided. PMID- 27179349 TI - Ultrastructure of the Periplastidial Compartment of the Diatom Phaeodactylum tricornutum. AB - Diatoms contain a secondary plastid that derives from a red algal symbiont. This organelle is limited by four membranes. The two outermost membranes are the chloroplast endoplasmic reticulum membrane (cERM), which is continuous with the host outer nuclear envelope, and the periplastidial membrane (PPM). The two innermost membranes correspond to the outer and inner envelope membranes (oEM and iEM) of the symbiont's chloroplast. Between the PPM and oEM lies a minimized symbiont cytoplasm, the periplastidial compartment (PPC). In Phaeodactylum tricornutum, PPC-resident proteins are localized in "blob-like-structures", which remain associated with plastids after cell disruption. We analyzed disrupted Phaeodactylum cells by focused ion beam scanning electron microscopy, revealing the presence of a vesicular network (VN) in the PPC, at a location consistent with blob-like structures. Presence of a VN in the PPC was confirmed in intact cells. Additionally, direct membrane contacts were observed between the PPM and nuclear inner envelope membrane at the level of the chloroplast-nucleus isthmus. This study provides insights into the PPC ultrastructure and opens perspectives on the function of this residual cytoplasm of red algal origin. PMID- 27179351 TI - 'Near death' thromboembolic episode following device closure of atrial septal defect. AB - Life-threatening pulmonary thromboembolism is a rare complication following device closure of an atrial septal defect (ASD). Our case is a 17-year old female who presented with a sudden cardiorespiratory arrest due to pulmonary thromboembolism, 5 months following a device closure of her ASD. She was successfully resuscitated and then underwent removal of the device with the associated clots and patch closure of the ASD. She made an uneventful recovery. We report this case to highlight that life-threatening thromboembolic complications can occur with ASD device closure. PMID- 27179350 TI - Self-collected genital swabs compared with cervicovaginal lavage for measuring HIV-1 and HSV-2 and the effect of acyclovir on viral shedding. AB - HIV-1 and HSV-2 are frequent genital co-infections in women. To determine how self-collected genital swabs compare to provider-collected cervicovaginal lavage, paired self-collected genital swabs and cervicovaginal lavage from women co infected with HIV-1 and HSV-2 were evaluated. Women were in an acyclovir clinical trial and their samples were tested for HIV-1 RNA (361 samples) and HSV-2 DNA (378 samples). Virus shedding, quantity and acyclovir effect were compared. HIV-1 and HSV-2 were more frequently detected in self-collected genital swabs: 74.5% of self-collected genital swabs and 63.6% of cervicovaginal lavage had detectable HIV-1 (p <= 0.001, Fisher's exact test) and 29.7% of self-collected genital swabs and 19.3% of cervicovaginal lavage had detectable HSV-2 (p <= 0.001) in the placebo month. Cervicovaginal lavage and self-collected genital swabs virus levels were correlated (Spearman's rho, 0.68 for HIV; 0.61 for HSV-2) and self collected genital swabs levels were generally higher. In multivariate modeling, self-collected genital swabs and cervicovaginal lavage could equally detect the virus-suppressive effect of acyclovir: for HIV-1, proportional odds ratios were 0.42 and 0.47 and for HSV-2, they were 0.10 and 0.03 for self-collected genital swabs and cervicovaginal lavage, respectively. Self-collected genital swabs should be considered for detection and measurement of HIV-1 and HSV-2 in clinical trials and other studies as they are a sensitive method to detect virus and can be collected in the home with frequent sampling. PMID- 27179352 TI - Towards improved migraine management: Determining potential trigger factors in individual patients. AB - Background Certain chronic diseases such as migraine result in episodic, debilitating attacks for which neither cause nor timing is well understood. Historically, possible triggers were identified through analysis of aggregated data from populations of patients. However, triggers common in populations may not be wholly responsible for an individual's attacks. To explore this hypothesis we developed a method to identify individual 'potential trigger' profiles and analysed the degree of inter-individual variation. Methods We applied N = 1 statistical analysis to a 326-migraine-patient database from a study in which patients used paper-based diaries for 90 days to track 33 factors (potential triggers or premonitory symptoms) associated with their migraine attacks. For each patient, univariate associations between factors and migraine events were analysed using Cox proportional hazards models. Results We generated individual factor-attack association profiles for 87% of the patients. The average number of factors associated with attacks was four per patient: Factor profiles were highly individual and were unique in 85% of patients with at least one identified association. Conclusion Accurate identification of individual factor-attack profiles is a prerequisite for testing which are true triggers and for development of trigger avoidance or desensitisation strategies. Our methodology represents a necessary development toward this goal. PMID- 27179353 TI - Secular trends in the timing of skeletal maturation as assessed by the cervical vertebrae maturation method. AB - Objective: To investigate the presence of secular trends in skeletal maturation of girls and boys as assessed by the use of cervical vertebrae bones. Materials and methods: The study compared two main groups: the first included data collected from the Denver growth study (1930s to 1960s) and the second included data collected from recent pretreatment records (1980s to 2010s) of patients from the orthodontic clinic of a North American University. The records from the two groups were all for Caucasian subjects. The sample for each group included 78 lateral cephalographs for girls and the same number for boys. The age of the subjects ranged from 7 to 18 years. Cervical vertebrae maturation (CVM) stages were directly assessed from the radiographs according to the method described by Hassel and Farman in which six CVM stages were designated from cervical vertebrae 2, 3, and 4. Results: The mean age of girls from the Denver growth study and girls from the university clinic in each of the six CVM stages was not different at P <=0.05. However, the mean age of boys from the two groups was not different only in stage 3 (P = 0.139) and stage 4 (P = 0.211). Conclusions: The results showed no evidence to indicate a tendency for earlier skeletal maturation of girls or boys. Boys in the university group started their skeletal maturation later than boys in the Denver group and completed their maturation earlier. Gender was a significant factor affecting skeletal maturation stages in both Denver and university groups. PMID- 27179354 TI - Clinical predictors of maxillary canine impaction: a novel approach using multivariate analysis. AB - Background: Ectopic eruption and/or impaction of maxillary permanent canines is a frequent problem in clinical dentistry. Previous studies aimed to identify potential associated factors and predictors for impacted maxillary canines have only used conventional univariate statistics, which does not allow the analysis of the interaction between and within variables. Multivariate data analysis (MVDA) is a better and more powerful tool for the integration and interpretation of complex datasets. Aim: The aim of this study was to validate previously explored predictors of permanent maxillary canine impaction using MVDA. Subjects and methods: This cohort study included all the patients referred during 2011 to Molndal Hospital, Sweden for surgical exposure of impacted canines (N = 45). Age- and gender-matched orthodontic patients (N = 45) with normally erupting canines comprised the control group. The age range for both groups was 11-17 years. The positions of the canine teeth (orthopantograms), the skeletal variables (profile radiographs), and dentoalveolar traits (casts) were evaluated as potential predictive factors for impaction. Results: None of the parameters evaluated with either profile radiography or casts were positively correlated with impacted maxillary canines, with the exception of the location of the already impacted canines, as identified by orthopantogram. Conclusion: No correlation between clinical variables and impaction was found using MVDA. Therefore, these variables could not be used as predictors of canine impaction. Other types of parameters, such as inheritance and molecular factors that regulate the biological mechanisms of the eruption process, need to be further investigated. PMID- 27179355 TI - Short- and Long-Term Effects of Parent Training for Preschool Children With or at Risk of ADHD: A Systematic Review and Meta-Analysis. AB - OBJECTIVE: The aim of the study was to synthesize the evidence of parent training (PT) as an early intervention for preschool children aged 2.5 to 6 years with ADHD or ADHD symptoms. METHOD: A systematic review and meta-analysis was conducted. RESULTS: Sixteen studies including 1,003 children were analyzed. Parent-rated outcomes revealed moderate effect sizes (ESs; Hedges' g) of 0.51 for ADHD symptoms, 0.4 for conduct problems, and 0.63 for negative parenting. Based on independent assessment, results were only significant for negative parenting. Parent-rated outcomes were sustained at follow-ups of 3 to 12 months. Program type, intervention modality, and child diagnostic status did not moderate the effect. CONCLUSION: PT was partially supported as an efficacious intervention for preschool children with ADHD or ADHD symptoms with moderate ESs on parent-rated outcomes, but no significant results on independently assessed ADHD symptoms. PMID- 27179356 TI - Probabilities of ADD/ADHD and Related Substance Use Among Canadian Adults. AB - OBJECTIVE: The aim of this study was to estimate the prevalence and probabilities of comorbidities between self-reported ADD/ADHD and smoking, alcohol binge drinking, and substance use disorders (SUDs) from a national Canadian sample. METHOD: Data were taken from the Public Use Microdata File of the 2012 Canadian Community Health Survey-Mental Health (N = 17 311). The prevalence of (a) smoking, (b) alcohol binge drinking, and (c) SUDs was estimated among those with an ADD/ADHD diagnosis versus those without an ADD/ADHD diagnosis. RESULTS: After controlling for potential socioeconomic and mental health covariates, self reported ADD/ADHD acted as a significant predictor for group membership in the heaviest smoking, heaviest drinking, and heaviest drug usage categories. CONCLUSION: Individuals self-reporting a diagnosis of ADD/ADHD were found to have a significantly higher likelihood of engaging in smoking and alcohol binge drinking, and were more likely to meet criteria for SUDs than individuals not reporting an ADD/ADHD diagnosis. PMID- 27179361 TI - Creation of an NCI comparative brain tumor consortium: informing the translation of new knowledge from canine to human brain tumor patients. AB - On September 14-15, 2015, a meeting of clinicians and investigators in the fields of veterinary and human neuro-oncology, clinical trials, neuropathology, and drug development was convened at the National Institutes of Health campus in Bethesda, Maryland. This meeting served as the inaugural event launching a new consortium focused on improving the knowledge, development of, and access to naturally occurring canine brain cancer, specifically glioma, as a model for human disease. Within the meeting, a SWOT (strengths, weaknesses, opportunities, and threats) assessment was undertaken to critically evaluate the role that naturally occurring canine brain tumors could have in advancing this aspect of comparative oncology aimed at improving outcomes for dogs and human beings. A summary of this meeting and subsequent discussion are provided to inform the scientific and clinical community of the potential for this initiative. Canine and human comparisons represent an unprecedented opportunity to complement conventional brain tumor research paradigms, addressing a devastating disease for which innovative diagnostic and treatment strategies are clearly needed. PMID- 27179362 TI - ATGL and DGAT1 are involved in the turnover of newly synthesized triacylglycerols in hepatic stellate cells. AB - Hepatic stellate cell (HSC) activation is a critical step in the development of chronic liver disease. During activation, HSCs lose their lipid droplets (LDs) containing triacylglycerol (TAG), cholesteryl esters (CEs), and retinyl esters (REs). Here we aimed to investigate which enzymes are involved in LD turnover in HSCs during activation in vitro. Targeted deletion of the Atgl gene in mice HSCs had little effect on the decrease of the overall TAG, CE, and RE levels during activation. However, ATGL-deficient HSCs specifically accumulated TAG species enriched in PUFAs and degraded new TAG species more slowly. TAG synthesis and levels of PUFA-TAGs were lowered by the diacylglycerol acyltransferase (DGAT)1 inhibitor, T863. The lipase inhibitor, Atglistatin, increased the levels of TAG in both WT and ATGL-deficient mouse HSCs. Both Atglistatin and T863 inhibited the induction of activation marker, alpha-smooth muscle actin, in rat HSCs, but not in mouse HSCs. Compared with mouse HSCs, rat HSCs have a higher turnover of new TAGs, and Atglistatin and the DGAT1 inhibitor, T863, were more effective. Our data suggest that ATGL preferentially degrades newly synthesized TAGs, synthesized by DGAT1, and is less involved in the breakdown of preexisting TAGs and REs in HSCs. Furthermore a large change in TAG levels has modest effect on rat HSC activation. PMID- 27179363 TI - Molecular species composition of plant cardiolipin determined by liquid chromatography mass spectrometry. AB - Cardiolipin (CL), an anionic phospholipid of the inner mitochondrial membrane, provides essential functions for stabilizing respiratory complexes and is involved in mitochondrial morphogenesis and programmed cell death in animals. The role of CL and its metabolism in plants are less well understood. The measurement of CL in plants, including its molecular species composition, is hampered by the fact that CL is of extremely low abundance, and that plants contain large amounts of interfering compounds including galactolipids, neutral lipids, and pigments. We used solid phase extraction by anion exchange chromatography to purify CL from crude plant lipid extracts. LC/MS was used to determine the content and molecular species composition of CL. Thus, up to 23 different molecular species of CL were detected in different plant species, including Arabidopsis, mung bean, spinach, barley, and tobacco. Similar to animals, plant CL is dominated by highly unsaturated species, mostly containing linoleic and linolenic acid. During phosphate deprivation or exposure to an extended dark period, the amount of CL decreased in Arabidopsis, accompanied with an increased degree in unsaturation. The mechanism of CL remodeling during stress, and the function of highly unsaturated CL molecular species, remains to be defined. PMID- 27179364 TI - [Unexpected outings of Alzheimer patients living in retirement homes: Therapeutic perspectives]. AB - OBJECTIVES: Various behavior disorders can occur during Alzheimer's disease, in particular unexpected outings. This article aims at understanding the diverse mechanisms present during a "runaway" episode, which can manifest in an acute way. The authors bring to light through clinical examples what is at work from a psychological perspective in order to create new accompaniment methods. METHOD: First, the authors reviewed the literature on runaway episodes in order to point out necessary themes for reflection. Then, from a Freudian theoretical model, they brought to light four fundamental mechanisms: hallucinations, false recognition, non-recognition, and recognition. These are mainly, although not exhaustively, understood from perceptions, memory-traces, indications of quality, and memories. This theory was questioned by means of presented clinical cases. Various post-Freudian models allowed the authors to emphasize the pathological experience in the role of perceptions and the functions, which come into play in the psychic economy. By going back and forth between theory and clinical cases, the authors underline the importance of perception in the phenomenon of unexpected outings. Finally, the Lacanian psychoanalytical theories provide a framework to question clinical cases but also provide answers to the criticisms found in the diverse reserved models. RESULTS: Through this study the authors hypothesize that the runaway episodes are not senseless but result from the interaction between the effects of the brain damage and the anxiety, which they arouse in the subjectivity of the person suffering from Alzheimer's. Leaning on false-recognitions, hallucinations, and non-recognitions such as were described in "Project for a scientific psychology", the authors put forward the hypothesis that these mechanisms express themselves in an imaginary relation, as in psychosis. CONCLUSION: The question of whether the runaway episodes of Alzheimer's sufferers can be classified as psychotic breakouts with a loss of touch with reality, or if the runaway episodes could be prevented by offering enough reassurance and support, is open to further debate. PMID- 27179365 TI - [Night-to-night variability of the obstructive sleep apnoea-hypopnoea syndrome]. AB - : The apnoea-hypopnoea index (AHI) is the primary measurement used to characterize the obstructive sleep apnoea-hypopnoea syndrome (OSAHS). Despite its popularity, there are limiting factors to its application such as night-to-night variability. AIM: To evaluate the variability of AHI in the OSAHS. PATIENTS AND METHODS: A prospective study was designed in our university hospital's sleep unit. Adults with clinical suspicion of OSAHS underwent 2 consecutive nights of polysomnographic recording. The population was divided in two groups according to an AHI>or<10. Patients with psychiatric disorders or professions that might result in sleep deprivation or an altered sleep/wake cycle were excluded. RESULTS: Twenty patients were enrolled. The mean age was 50.6+/-9.3 years. OSAHS was mild in 4 cases, moderate in 6 cases and severe in 8 cases. AHI was less than 5 in two cases. AHI values were not significantly altered throughout both recording nights (33.2 vs. 31.8 events/h). A significant positive correlation was found between AHI measured on the first and the second night. However, a significant individual variability was noted. Comparison between both patient's groups showed a correlation between AHI and the body mass index. CONCLUSION: This study demonstrates that the AHI in OSAHS patients is well correlated between two consecutive nights. However, a significant individual variability should be taken into consideration, especially when AHI is used in the classification of OSAHS or as a criterion of therapeutic success. PMID- 27179366 TI - Real-time pose estimation of devices from x-ray images: Application to x-ray/echo registration for cardiac interventions. AB - In recent years, registration between x-ray fluoroscopy (XRF) and transesophageal echocardiography (TEE) has been rapidly developed, validated, and translated to the clinic as a tool for advanced image guidance of structural heart interventions. This technology relies on accurate pose-estimation of the TEE probe via standard 2D/3D registration methods. It has been shown that latencies caused by slow registrations can result in errors during untracked frames, and a real-time ( > 15 hz) tracking algorithm is needed to minimize these errors. This paper presents two novel similarity metrics designed for accurate, robust, and extremely fast pose-estimation of devices from XRF images: Direct Splat Correlation (DSC) and Patch Gradient Correlation (PGC). Both metrics were implemented in CUDA C, and validated on simulated and clinical datasets against prior methods presented in the literature. It was shown that by combining DSC and PGC in a hybrid method (HYB), target registration errors comparable to previously reported methods were achieved, but at much higher speeds and lower failure rates. In simulated datasets, the proposed HYB method achieved a median projected target registration error (pTRE) of 0.33 mm and a mean registration frame-rate of 12.1 hz, while previously published methods produced median pTREs greater than 1.5 mm and mean registration frame-rates less than 4 hz. In clinical datasets, the HYB method achieved a median pTRE of 1.1 mm and a mean registration frame rate of 20.5 hz, while previously published methods produced median pTREs greater than 1.3 mm and mean registration frame-rates less than 12 hz. The proposed hybrid method also had much lower failure rates than previously published methods. PMID- 27179367 TI - Slic-Seg: A minimally interactive segmentation of the placenta from sparse and motion-corrupted fetal MRI in multiple views. AB - Segmentation of the placenta from fetal MRI is challenging due to sparse acquisition, inter-slice motion, and the widely varying position and shape of the placenta between pregnant women. We propose a minimally interactive framework that combines multiple volumes acquired in different views to obtain accurate segmentation of the placenta. In the first phase, a minimally interactive slice by-slice propagation method called Slic-Seg is used to obtain an initial segmentation from a single motion-corrupted sparse volume image. It combines high level features, online Random Forests and Conditional Random Fields, and only needs user interactions in a single slice. In the second phase, to take advantage of the complementary resolution in multiple volumes acquired in different views, we further propose a probability-based 4D Graph Cuts method to refine the initial segmentations using inter-slice and inter-image consistency. We used our minimally interactive framework to examine the placentas of 16 mid-gestation patients from MRI acquired in axial and sagittal views respectively. The results show the proposed method has 1) a good performance even in cases where sparse scribbles provided by the user lead to poor results with the competitive propagation approaches; 2) a good interactivity with low intra- and inter operator variability; 3) higher accuracy than state-of-the-art interactive segmentation methods; and 4) an improved accuracy due to the co-segmentation based refinement, which outperforms single volume or intensity-based Graph Cuts. PMID- 27179368 TI - Clinical significance of coryneform Gram-positive rods from blood identified by MALDI-TOF mass spectrometry and their susceptibility profiles - a retrospective chart review. AB - With the advent of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), most Gram-positive rods (GPRs) are readily identified; however, their clinical relevance in blood cultures remains unclear. Herein, we assessed the clinical significance of GPRs isolated from blood and identified in the era of MALDI-TOF MS. A retrospective chart review of patients presenting to the Mayo Clinic, Rochester, MN, from January 1, 2013, to October 13, 2015, was performed. Any episode of a positive blood culture for a GPR was included. We assessed the number of bottles positive for a given isolate, time to positivity of blood cultures, patient age, medical history, interpretation of culture results by the healthcare team and whether infectious diseases consultation was obtained. We also evaluated the susceptibility profiles of a larger collection of GPRs tested in the clinical microbiology laboratory of the Mayo Clinic, Rochester, MN from January 1, 2013, to October 31, 2015. There were a total of 246 GPRs isolated from the blood of 181 patients during the study period. 56% (n = 101) were deemed contaminants by the healthcare team and were not treated; 33% (n = 59) were clinically determined to represent true bacteremia and were treated; and 8% (n = 14) were considered of uncertain significance, with patients prescribed treatment regardless. Patient characteristics associated with an isolate being treated on univariate analysis included younger age (P = 0.02), identification to the species level (P = 0.02), higher number of positive blood culture sets (P < 0.0001), lower time to positivity (P < 0.0001), immunosuppression (P = 0.03), and recommendation made by an infectious disease consultant (P = 0.0005). On multivariable analysis, infectious diseases consultation (P = 0.03), higher number of positive blood culture sets (P = 0.0005) and lower time to positivity (P = 0.03) were associated with an isolate being treated. 100, 83, 48 and 34% of GPRs were susceptible to vancomycin, meropenem, penicillin and ceftriaxone, respectively. PMID- 27179369 TI - Morbidity and mortality among patients with respiratory syncytial virus infection: a 2-year retrospective review. AB - Previous studies have demonstrated high morbidity and mortality for adult patients with respiratory syncytial virus (RSV) infection. We performed a retrospective, multicenter, two-year chart review of all patients (n = 334) testing positive for RSV by the ProFlu + ((r)) Influenza A/B and RSV assay (Hologic, Bedford, MA). We analyzed indicators of morbidity and mortality in children <6 years old, immunocompetent and immunosuppressed adults, and transplant patients. Significant morbidity and mortality was observed among hematopoietic stem cell transplant patients (7.3%, 60-day mortality), solid organ transplant patients (13.3%, 60-day mortality), and COPD patients (12.8%, 60-day mortality). Of the patients positive for RSV, 144 (43.1%) of 334 received antibacterials or antifungals following diagnosis. Of these patients, a bacterial or fungal pathogen was not recovered from 60% of cases. Despite advances in RSV treatment, certain populations appear to be inadequately treated, while others appear to be inappropriately treated with unnecessary antimicrobials. PMID- 27179370 TI - Partners' perspective on care-system support before, during and after childbirth in relation to parenting roles. AB - OBJECTIVES: To explore (i) ways in which partners experience support from care systems before, during, and after childbirth in relation to their parenting roles and (ii) ways in which support can improve. METHODS: Four focus group interviews (n = 17; median age = 35; age range = 24-46) and inductive content analysis. RESULTS: Analysis revealed the following three categories: (1) Care staff include or exclude in relation to partners' parenting role; (2) Care systems continuity; (3) Being a supportive partner. The latent content of the categories was formulated into a theme: being engaged and wanting to be included. CONCLUSIONS: Because partners are engaged parents, who support the woman giving birth, they must feel included during pregnancy, birth, and postpartum care and during encounters within child health care units. This would require (i) information that directly targets partners before and after childbirth, (ii) specially adapted venues for parent education, and (iii) personal, partner-focused discussions with care staff. PMID- 27179371 TI - Sense of coherence among healthy Norwegian women in postnatal care: Dimensionality reliability and construct validity of the Orientation to Life Questionnaire. AB - OBJECTIVE: Salutogenesis focuses on identifying the causes of health rather than the causes of illness, and in this way offers a health promotion framework for maternity services. The application of salutogenesis theory in empirical studies of healthy women in maternity care appears to be rare, and mostly incomplete. The objective of this study is to examine the psychometric properties of the Orientation to Life Questionnaire (OLQ) assessing sense of coherence (SOC) in a population of healthy Norwegian women during the postnatal period. METHODS: Self reported cross-sectional data were collected from 183 women six weeks into the postnatal period. The data were analysed by descriptive statistics and confirmative factor analysis. RESULTS: Discriminant validity was supported by significant negative correlations between SOC, meaningfulness, comprehensibility, manageability, anxiety and depression. Inter-item consistency with Cronbach's alpha (0.62-0.87) and composite reliability (0.60-0.92) revealed acceptable to good values approving the reliability. The original one-dimensional concept of sense of coherence was confirmed in this study. However, in accordance with previous research, some misspecifications in reference to correlated error variances between the items OLQ2 and OLQ3 were discovered. CONCLUSION: This study lends support to the original one-dimensional construct of sense of coherence, and sheds more light upon the troublesome pair of items OLQ2-OLQ3. Further studies are required. However, based on our results, a rewording or deletion of one of these two items seems necessary in order to achieve a reliable and valid instrument measuring SOC among healthy postnatal women. PMID- 27179372 TI - Lebanese women and sexuality: A qualitative inquiry. AB - OBJECTIVES: This study explores the meanings middle-aged Lebanese women attribute to sexuality and sexual life and how these constructs are shaped socially, culturally, and politically. STUDY DESIGN: Using a qualitative design, data generation comprised semistructured individual interviews (n = 18) and one focus group (n = 5) with Lebanese women aged 40-55 years. Framework analysis was used for data analysis. RESULTS: Inductive analysis identified four themes: Sexuality as imposed by sociocultural and gender norms; sexuality as a symbol of youthful femininity; sexual life as a fundamental human need; and sexual life as a marital unifier and family stabiliser. Findings show that women's sexual self is largely defined based on men's needs. Women sacrifice themselves to maintain family cohesiveness, which they regard as the core of society. However, some women challenged social norms and therefore bringing new meanings to their sexuality. CONCLUSION: This study offers new contextual information about the understanding of sexuality of middle-aged women within a Lebanese context, where the topic is not openly discussed. New insights are important to provide women with professional support that is culturally sensitive and appropriate. PMID- 27179373 TI - The perceived role of clinicians in pregnancy prevention among young Black women. AB - OBJECTIVE: The purpose of this study is to identify young Black women's attitudes toward clinicians and understand how they affect contraceptive behavior. STUDY DESIGN AND MAIN OUTCOME MEASURES: We conducted semi-structured qualitative interviews with women aged 18-23 who self-identified as Black or African-American and analyzed data using techniques informed by grounded theory. Initial codes were grouped thematically, and these themes into larger concepts. RESULTS: Participants discussed two salient concepts related to pregnancy prevention: (1) sexual responsibility and self-efficacy and (2) the perceived limited role of health care clinicians. Women portrayed themselves as in control of their contraceptive decision-making and practices. Many viewed their life plan, to finish school and gain financial stability, as crucial to their resolve to use contraception. Participants gathered information from various sources to make their own independent decision about which method, if any, was most appropriate for their needs. Most had limited expectations of clinicians and considered in depth conversations about details of contraceptive use to be irrelevant and unnecessary. CONCLUSION: These findings help understand factors contributing to contraceptive decision-making. The patient-clinician interaction is a necessary focus of future research to improve sexual health discussions and understand if and what aspects of this interaction can influence behavior. PMID- 27179374 TI - Mediolateral versus lateral episiotomy and their effect on postpartum coital activity and dyspareunia rate 3 and 6 months postpartum. AB - OBJECTIVES: Comparison of the effects of two episiotomy types on sexual activity, dyspareunia and overall satisfaction after childbirth. STUDY DESIGN: A prospective follow-up study of a randomized comparative trial evaluating peripartum outcome of a vaginal delivery after mediolateral (MLE) or lateral (LE) episiotomy. MAIN OUTCOME MEASURES: The participants completed questionnaires regarding sexual activity, dyspareunia, perineal pain, aesthetic appearance and overall satisfaction 3 (3M) and 6 months (6M) postpartum. RESULTS: A total of 648 women were available for the analyses (306 MLE, 342 LE). The groups showed no difference regarding resumption and regularity of sex, timing of resumption, frequency and intensity of dyspareunia, perineal pain, aesthetic appearance or overall satisfaction 3M or 6M postpartum. 98.0% of women after MLE and 97.7% after LE resumed sexual intercourse within 6M after delivery (p = 0.74). In the same period 15.6% of women after MLE and 16.1% after LE suffered from considerable dyspareunia (p = 0.86). CONCLUSIONS: Quality of sexual life and perception of perineal pain after MLE is equivalent to LE. PMID- 27179375 TI - Swedish women's food habits during pregnancy up to six months post-partum: A longitudinal study. AB - OBJECTIVES: Diet influences the health of the foetus and the woman during pregnancy and later in life. It is therefore important to investigate pregnant women's food habits. The aim of this study was to describe women's food habits during pregnancy and up to six months post-partum. STUDY DESIGN: A Food Frequency Questionnaire (VIP-FFQ) was distributed to 163 pregnant women on five occasions during and after pregnancy. Data were analysed using Friedman's ANOVA and a Bonferroni post-hoc test. MAIN OUTCOME MEASURES: Food habits in relation to the National Food Agency's (NFA) food index. RESULTS: The pregnant women's diets were inadequate according to the NFA food index. A tendency towards an even poorer diet after delivery was identified, something which was related to an increased intake of discretionary food, e.g. sweets, cakes, cookies, crisps, ice cream, and decreased intake of fruit and vegetable. The alcohol consumption was low throughout. CONCLUSIONS: The food habits during pregnancy were inadequate compared to recommendations and these habits became unhealthier after delivery. These suggest that dietary counselling needs to be more effective and continued into the lactating period. An increased focus should be given to healthy eating from the life course perspective, not just focus on effects on the foetus and pregnancy outcomes. PMID- 27179376 TI - The role of knowledge in the contraceptive behaviour of sexually active young people in state care. AB - AIM: To analyse the role of sex-focused knowledge in the contraceptive behaviour of sexually active young people in state care. METHODS: The sample consisted of 19 care leavers (young people previously in state care) aged 18-22 years, 16 females and 3 males. In-depth interviewing was the method of data collection, and a qualitative strategy resembling modified analytical induction was used to analyse data. FINDINGS: Findings indicated that a lack of information was not the sole or even the primary reason for engaging in unsafe sexual practices. Other factors such as ambivalence to becoming pregnant also featured in participants' accounts. Several participants conveyed a relatively weak sense of agency about consistently using contraception. A small number of participants expressed a strong determination to avoid pregnancy, and these appeared to have a level of anxiety about becoming pregnant that motivated them to engage with knowledge about contraception and its use. CONCLUSION: Lack of sex-focused information is just one aspect of a myriad of complex factors, including socioeconomic disadvantage and/or emotional deprivation, that influence contraceptive behaviour. PMID- 27179377 TI - The experiences of husbands of primiparas with depressive or anxiety disorders during the perinatal period. AB - OBJECTIVES: During the perinatal period, husbands take the key role as essential supporter of wives with mental illness. The aim of this study was to explore the experiences of husbands of primiparas with depressive or anxiety disorders. METHODS: A qualitative descriptive design was used in the study. In-depth interviews were held one to two months after childbirth and results were analyzed using a constant comparative method. RESULTS: We approached ten couples and seven husbands agreed to be interviewed. From interviews, four categories emerged. They are "Husband is committed to decision making by exploring the impact of pregnancy", "The husband's burden depends on his wife's mental status and the relationship between her parents", "The preciousness of baby offsets the new burden," and "Continuous process of trial and error dealing with wife's mental status". CONCLUSIONS: For many years prior to pregnancy, husbands had been alone in trying to help their wives through trial and error. After childbirth they accepted the new child-centered lifestyle and supported their wives' mental health. Healthcare providers are needed to become advisors not only to pregnant women but also to their husbands and build a stable support system with members such as psychiatrists, obstetricians and midwives. PMID- 27179378 TI - Cross-cultural development and psychometric evaluation of a measure to assess fear of childbirth prior to pregnancy. AB - BACKGROUND: Assessment of childbirth fear, in advance of pregnancy, and early identification of modifiable factors contributing to fear can inform public health initiatives and/or school-based educational programming for the next generation of maternity care consumers. We developed and evaluated a short fear of birth scale that incorporates the most common dimensions of fear reported by men and women prior to pregnancy, fear of: labour pain, being out of control and unable to cope with labour and birth, complications, and irreversible physical damage. METHODS: University students in six countries (Australia, Canada, England, Germany, Iceland, and the United States, n = 2240) participated in an online survey to assess their fears and attitudes about birth. We report internal consistency reliability, corrected-item-to-total correlations, factor loadings and convergent and discriminant validity of the new scale. RESULTS: The Childbirth Fear - Prior to Pregnancy (CFPP) scale showed high internal consistency across samples (alpha > 0.86). All corrected-item-to total correlations exceeded 0.45, supporting the uni-dimensionality of the scale. Construct validity of the CFPP was supported by a high correlation between the new scale and a two-item visual analogue scale that measures fear of birth (r > 0.6 across samples). Weak correlations of the CFPP with scores on measures that assess related psychological states (anxiety, depression and stress) support the discriminant validity of the scale. CONCLUSION: The CFPP is a short, reliable and valid measure of childbirth fear among young women and men in six countries who plan to have children. PMID- 27179379 TI - Swedish fathers contemplate the difficulties they face in parenthood. AB - OBJECTIVE: The aim was to explore what concerns Swedish fathers had about parenting difficulties at two months after the birth of their baby. METHODS: Self report questionnaires were used and data were analyzed with mixed methods. RESULTS: Thirty percent of the 827 fathers reported concerns about the difficulties of parenthood. The theme 'Managing the demands of being a father' emerged and was based on concerns about how to raise the baby, having enough money, health issues, lack of time and finding balance in the new family pattern. Financial worries, feeling less positive about expecting a baby, and self reported poor emotional health were related to fathers who perceived parenthood as difficult. CONCLUSION: Experienced fathers as well as new fathers expressed similar concerns about parenthood. Preparation classes for reassurance and skills coaching about child raising may provide important support for fathers. This is especially important for fathers who may have poor emotional health or who may not be feeling positive about expecting a baby. Policy-makers and health care providers should recognize that offering support for all fathers benefits not only men, but also their children, and their partners and can help encourage egalitarian practices at home and work. PMID- 27179380 TI - The media as a critical determinant of the sexual and reproductive health of adolescents in Ibadan, Nigeria. AB - PURPOSE: Findings on the influences of the media on the sexual health of adolescents in vulnerable communities in Ibadan are presented. METHODS: Phase I of the WAVE study in Ibadan was conducted among participants purposively selected from disadvantaged communities in Ibadan North Local Government Area (LGA). Qualitative research methods (key informant interviews, in-depth interviews, community mapping and focus group discussions as well as photovoice sessions) were utilized. RESULTS: A total of 132 key informants and adolescents (aged 15-19 years) participated. The key informants were teachers, youth workers, and religious leaders working with adolescents within the LGA. Respondents mentioned a number of media technologies (such as television, cellphones, computers, the Internet as well as online and hard copy novels) that adolescents are exposed to in contemporary times. They said these had positive and negative influences on them. Adolescents often looked up information on the Internet although it was mostly used as a means of meeting and communicating with friends. Respondents stated that the media had a strong influence on adolescents' sexual and reproductive health especially regarding dating, relationships, and sexual practices. It also exposed them to pornography and Internet fraud. CONCLUSIONS: The study highlighted the important role the media plays in the sexual health of adolescents in Ibadan. Intervention programmes need to make use of this medium to reach out to more adolescents and measures should be instituted to prevent adolescents from misusing the media. PMID- 27179381 TI - Fathers' care of the newborn infant after caesarean section in Chile: A qualitative study. AB - BACKGROUND: In Chilean hospitals the current model of care after caesarean section is to separate newborn infants from both parents. The care of newborn infants and the parents' experience immediately after caesarean section requires further exploration. AIM: To describe fathers' experiences and perceptions of being the primary caregiver to their newborn infant during the first 90 minutes after caesarean section in a public general maternity hospital setting in Santiago de Chile. METHOD: The questionnaire was one part of a larger research programme named: "Caregiving Models after Elective Caesarean Section - Parents' perceptions and effects on infants' wellbeing". Four open ended questions were used to gather written text on the experiences and perceptions of 95 fathers who were the primary caregiver to their newborn infant. Ethical approval was obtained from the Ethics Committee, Scientific Assessment Metropolitan Health Service South East. Systematic text condensation according to Malterud's description was used for analysis of the written text. FINDINGS: Two themes were identified: "understanding the first moment of life" and "shared responsibility for future family life" with each theme divided into six categories. CONCLUSION: This study concludes by arguing that in situations where the mother is unavailable or unable to provide basic care, the father should be supported to care for the newborn infant. CLINICAL IMPLICATIONS: Parents should be made aware of the benefits of this caring model especially when mother and baby have been separated after birth. PMID- 27179382 TI - Counseling for childbirth fear - a national survey. AB - BACKGROUND: Counseling by experienced midwives is offered to women with childbirth fear in most obstetric clinics in Sweden, but information about the content of such counseling is lacking. AIM: To study comprehensiveness, content and organization of the midwife-led counseling for childbirth fear in all obstetric clinics in Sweden. METHODS: In this cross-sectional study, data were collected using a questionnaire sent to all obstetric clinics in Sweden (n = 45); a total of 43 clinics responded. Descriptive and one-way ANOVA was used in the analysis. RESULTS: All responding obstetric clinics in Sweden offer midwife-led counseling to women with childbirth fear. Major differences were found regarding the time allocated to counseling, with a range between 5.7 and 47.6 minutes per childbirth. Supplementary education for midwives and the availability of treatment options varied at the different clinics and were not associated with the size of the clinic. CONCLUSION: The midwife-led counseling conducted at the different Swedish obstetric clinics showed considerable disparities. Women with childbirth fear would benefit from care on equal terms irrespective of place of residence. Consequently, it would be valuable to develop a national healthcare program for childbirth fear. PMID- 27179383 TI - Under scrutiny: Midwives' experience of intrapartum transfer from home to hospital within the context of a planned homebirth in Western Australia. AB - BACKGROUND: Women's experience of homebirth has been a focus of research, with limited international research and no Australian evidence of the experiences of midwives in relation to their experience of intrapartum transfers within the context of a planned homebirth. OBJECTIVE: To explore the experience of Western Australian midwives involved in an intrapartum transfer from home to hospital. METHODS: A descriptive phenomenological study was conducted. Women who elect to have a homebirth in Western Australia have the choice of care from privately practising midwives or a publicly funded program. Midwives who were currently practising or had practised within the past three years and experienced an intrapartum transfer were invited to participate. In-depth interviews were conducted with 13 midwives and data analysed using the Stevick-Colaizzi-Keen method. RESULTS: Analysis revealed an overarching theme "under scrutiny" which captured four themes: "decision to transfer: getting the timing right"; "reception at the hospital: welcoming or not"; "maintaining continuity of carer" and "reflections: coming to terms with the experience". CONCLUSION: The decision to transfer to hospital represents a profound shift in expectations for the woman and midwife that is often not recognised by hospital staff. Intrapartum transfer is a challenging clinical decision for all parties; midwives, women, partners and health services. Increased effort by maternity health professionals to improve communication and collaboration must be a priority to better support women and their partners who make an informed decision to have a planned homebirth. PMID- 27179384 TI - Obstetric management in vacuum-extraction deliveries. AB - OBJECTIVE: The aim of this observational study was to describe the obstetric management in vacuum extraction (VE) deliveries and to compare these findings to instructions in clinical guidelines on VE. METHODS: In 2013, detailed data on management of 600 VE cases were consecutively collected from six different delivery units in Sweden. Each unit also contributed their own clinical VE guideline. RESULTS: In total, 93% of the VEs ended with a vaginal delivery while 7% failed and were converted to an emergency cesarean section. In 2.3% extraction time exceeded 20 minutes, and in 6% more than six pulls were used to deliver the fetus. Cup detachment occurred in 14.6%, and fundal pressure was used in 11% of the deliveries. In 2.3%, fetal station was assessed as above the level of the maternal ischial spines. The clinical guidelines on VE varied in scope and content between units, and were often incomplete according to best practice. CONCLUSION: The vast majority of the VEs were conducted in accordance with safety recommendations. However, in a few extractions, safety rules were disregarded and more than six pulls or an extraction time of more than 20 minutes were used to complete the delivery. PMID- 27179385 TI - Naegele's rule revisited. AB - Recent literature suggests that Franz Carl Naegele's (1778-1851) rule for estimating the date of delivery has been misinterpreted, resulting in this being brought forward by five days. Baskett and Nagele's work underpinning this argument has become widely accepted and quoted in obstetrical and midwifery textbooks. However, our re-examination of Naegele's original statements does not support the recent findings. On the contrary, the original textbooks of Naegele clearly advise taking the first day of menstruation for the calculation of the date of delivery. PMID- 27179386 TI - Applying an intervention framework to assess North Carolina's adolescent pregnancy prevention efforts. AB - PURPOSE: We assessed the extent to which implementing adolescent pregnancy prevention programs in conjunction with three level implementation strategies reduces adolescent pregnancy rates at the county-level in North Carolina (NC). METHODS: Fixsen and colleagues' (2005) three levels of implementation were used to organize the prevention strategies: core (e.g., training, fidelity monitoring), organizational (e.g., administrative support), and external (e.g., community resources). RESULTS: Counties that had adolescent friendly clinic/services (external) were more likely to report lower adolescent pregnancy rates in comparison to counties that did not have access to such services. CONCLUSIONS: Findings suggest external implementation strategies are key to reducing adolescent pregnancy rates. PMID- 27179387 TI - Clinical Outcome of Isolated Popliteal Artery Aneurysms Treated with a Heparin bonded Stent Graft. AB - OBJECTIVE: The use of self-expanding stent grafts for treatment of popliteal artery aneurysms (PAA) is a matter of debate, although several studies have shown similar results compared with open surgery. In recent years, a new generation stent graft, with heparin-bonding technology, became available. The aim of this study is to present the results of endovascular PAA repair with heparin-bonded stent grafts. METHODS: Data on all patients with PAA treated with a heparin bonded polytetrafluoroethylene (ePTFE) stent graft between April 2009 and March 2014 were gathered in a database and retrospectively analyzed. Data were collected from four participating hospitals. Standard follow-up consisted of clinical assessment, and duplex ultrasound at 6 weeks, 6 months, 12 months, and annually thereafter. The primary endpoint of the study was primary patency. Secondary endpoints were primary-assisted and secondary patency and limb salvage rate. RESULTS: A total of 72 PAA was treated in 70 patients. Mean age was 71.2 +/ 8.5 years and 93% were male (n = 65). The majority of PAA were asymptomatic (78%). Sixteen cases (22%) had a symptomatic PAA, of which seven (44%) presented with acute ischemia. Early postoperative complications occurred in two patients (3%). Median follow-up was 13 months (range 0-63 months). Primary patency rate at 1 year was 83% and after 3 years 69%; primary assisted patency rate was 87% at 1 year and 74% after 3 years. Secondary patency rate was 88% and 76% at 1 and 3 years, respectively. There were no amputations during follow-up. CONCLUSION: Endovascular treatment of PAA with heparin-bonded stent grafts is a safe treatment option with good early and mid-term patency rates comparable with open repair using the great saphenous vein. PMID- 27179388 TI - Vagoglossopharyngeal neuralgia revealed through predominant digestive vagal manifestations. Case report and literature review. AB - Vagoglossopharyngeal neuralgia is a rare pathology whose atypical forms, dominated by syncopal manifestations, are still rarer. Although the territory of the vagus nerve involves, beyond the cardiovascular system, the respiratory and the digestive systems, there is no report in literature of atypical forms other than syncopal. Therefore, the authors were prompted to report the case of a patient whose vagoglossopharyngeal neuralgia was predominantly revealed by digestive symptoms. A 58-year-old patient presented with stereotypical severe digestive disturbances including nausea, vomiting and diarrhoea. High definition cranial MRI showed a neurovascular conflict between the posterior inferior cerebellar artery and the IXth and Xth nerves, on the right side. A microsurgical decompression was carried out which confirmed the vascular compression and successful transposition of the artery. One year after the surgery, the patient was free from all painful and digestive symptoms. A survey of the literature did not find any reference to digestive symptoms together with the neuralgia; only a syncopal type of cardiac symptoms related to the parasympathetic nervous system were described. The hypothesis was that the revealing digestive symptoms are linked to a similar parasympathetic mechanism, implying the visceral component of the Xth cranial nerve. PMID- 27179389 TI - Extended endoscopic endonasal approach to clival and paraclival tumors: Indications and limits. AB - OBJECTIVE: To report our experience with the Extended endoscopic endonasal approach (EEEA) for clival and paraclival tumors. DESIGN: Retrospective analysis of a consecutive series of patients. RESULTS: Eleven patients were considered: 3 chordomas, 3 meningiomas, 3 metastatic lesions, one chondroma and one chondrosarcoma. Gross total resection (GTR) was achieved in all chordomas and in chondromas with patients free of disease at the last follow-up. The chondrosarcoma was first operated on using a transfacial approach and endoscopy was performed for local progression with subtotal resection. The meningiomas were treated by a combination of transcranial and endoscopic approach due to their extension. The resection was subtotal and the residue treated by radiosurgery. Two patients with rhinopharyngeal carcinoma underwent palliative debulking. One metastatic melanoma that underwent GTR experienced remission. Two patients had postoperative cranial nerve palsy. No other complications were observed. CONCLUSIONS: EEEA allows a direct access to the skull base. Through a minimal access, it limits the incidence of neurological morbidities. For midline epidural clival tumors, EEEA allows a total excision. It also offers an excellent access to the clival component of intradural lesions. A combined approach permits good tumor control with minimal complications. PMID- 27179390 TI - Dynein Dysfunction Reproduces Age-Dependent Retromer Deficiency: Concomitant Disruption of Retrograde Trafficking Is Required for Alteration in beta-Amyloid Precursor Protein Metabolism. AB - It is widely accepted that beta-amyloid (Abeta) protein plays a pivotal role in Alzheimer disease pathogenesis, and accumulating evidence suggests that endocytic dysfunction is involved in Abeta pathology. Retromer, a conserved multisubunit complex, mediates the retrograde transport of numerous kinds of cargo from endosomes to the trans-Golgi network. Several studies have found that retromer deficiency enhances Abeta pathology both in vitro and in vivo. Cytoplasmic dynein, a microtubule-based motor protein, mediates minus-end-directed vesicle transport via interactions with dynactin, another microtubule-associated protein that also interacts with retromer. Aging attenuates the dynein-dynactin interaction, and dynein dysfunction reproduces age-dependent endocytic disturbance, resulting in the intracellular accumulation of beta-amyloid precursor protein (APP) and its beta-cleavage products, including Abeta. Here, we report that aging itself affects retromer trafficking in cynomolgus monkey brains. In addition, dynein dysfunction reproduces this type of age-dependent retromer deficiency (ie, the endosomal accumulation of retromer-related proteins and APP. Moreover, we found that knockdown of Rab7, Rab9, or Rab11 did not alter endogenous APP metabolism, such as that observed in aged monkey brains and in dynein-depleted cells. These findings suggest that dynein dysfunction can cause retromer deficiency and that concomitant disruption of retrograde trafficking may be the key factor underlying age-dependent Abeta pathology. PMID- 27179391 TI - Association between Internet gaming disorder and adult attention deficit and hyperactivity disorder and their correlates: Impulsivity and hostility. AB - Internet gaming disorder (IGD) and attention deficit and hyperactivity disorder (ADHD) are associated with impulsivity and hostility. This study evaluated the associations among ADHD, impulsivity, hostility, and IGD. We recruited 87 individuals with IGD and 87 controls without a history of IGD. All participants underwent a diagnostic interview based on the DSM-5 IGD criteria and DSM-IV-TR ADHD criteria and completed a questionnaire regarding impulsivity and hostility. The information from the diagnostic interviews was assessed using the clinical global impression scale. The results suggested that IGD is associated with ADHD among young adults and that young adults with both IGD and ADHD have higher impulsivity and hostility. Furthermore, impulsivity and hostility mediate the association between ADHD and IGD. Thus, ADHD is a common comorbidity of IGD among young adults, and impulsivity and hostility are major factors involved in comorbid ADHD and IGD. Young adults with ADHD should be thoroughly assessed, particularly for their impulsivity and hostility, and interventions for IGD should be developed. PMID- 27179392 TI - Use of a fluorescent marker for assessing hospital bathroom cleanliness. AB - A fluorescent marker was used to assess the efficacy of daily cleaning in hospital en suite bathrooms. We applied the marker on 218 surfaces and we assigned a score according how completely the mark had been removed. We found significant statistical differences among different surfaces and wards (P < .05). Microbiologic contamination and marker removal score did not seem to be correlated. Differences in cleanliness may indicate discrepancies in cleaning procedures. Fluorescent marker proved to be a practical and effective method and it could be adopted as a first-level control system to assess hospital cleanliness. PMID- 27179393 TI - Risk factors for deep sternal wound infection after cardiac surgery: Influence of red blood cell transfusions and chronic infection. AB - BACKGROUND: Deep sternal wound infection (DSWI) following cardiac surgery is a serious complication, but risk factors associated with DSWI have not been fully elucidated. METHODS: We analyzed all DSWI cases at our institution from 2010-2013 in adult cardiac median sternotomy cases, based on Society of Thoracic Surgeons or National Healthcare Safety Network definitions, but with 1-year surveillance postsurgery. Controls were matched 3:1 per case for procedure, age, and year of surgery. Demographic and operative data were pulled from Society of Thoracic Surgeons database and chart review. Potential variables were evaluated using univariate and multivariate conditional logistic regression. RESULTS: Out of 1,894 surgeries performed, 39 DSWI cases (2%) and 117 controls were identified. In univariate analyses, patients with red blood cell (RBC) transfusion >= 4 units, any platelet transfusion, previous infections, and chronic infections were associated with higher DSWI. RBC transfusion >= 4 units (P = .037) and chronic infections (P = .029) remained significant risk factors for DSWI in multivariate analysis. Preoperative anemia alone was not associated with more DSWI, but its interaction with RBC transfusion >= 4 units was significant. CONCLUSIONS: High volume RBC transfusions and chronic infections were strongly associated with DSWI in our population and represent potentially modifiable areas for improvement. PMID- 27179394 TI - A novel infection prevention approach: Leveraging a mandatory electronic communication tool to decrease peripherally inserted central catheter infections, complications, and cost. AB - BACKGROUND: Peripherally inserted central catheters (PICCs) removed prematurely for unconfirmed infection or thrombosis lead to subsequent reinsertions and associated complications. To improve clinical quality, a mandatory electronic communication tool (MECT) based on clinical practice guidelines was mandated for all inpatient adult PICCs in an academically affiliated tertiary medical center. This MECT facilitated early communication and specialized evaluation with the PICC team for any complications related to PICCs. METHODS: A historical cohort study was conducted. Quality and cost measurements for 200 PICCs postinstitution of a MECT were compared with 200 PICCs 12 months prior. PICC removal and complication rates were compared for the 2 cohorts. RESULTS: Significant outcomes included a central-line associated blood stream infection rate that changed from 1.38/1,000 catheter days to 0/1,000 catheter days, 0 provider-led premature PICC removals, an overall 84% decrease in premature PICC removals (from 16%-2.5%; P < .0001), a decrease in the total complication rate from 45.5%-24% (P < .0001), and 25% reduction in radiology costs. CONCLUSION: A novel infection prevention approach leveraging a MECT resulted in 0 central line-associated bloodstream infections and provider-led premature PICC removals. PMID- 27179396 TI - Encapsulated omental necrosis after Roux-en-Y gastric bypass. PMID- 27179397 TI - Comment on: Characteristics of adolescents with poor mental health after bariatric surgery. PMID- 27179395 TI - Carbapenem-resistant Enterobacteriaceae and endoscopy: An evolving threat. AB - BACKGROUND: Several clusters of Carbapenem-resistant Enterobacteriaceae (CRE) infections associated with contaminated endoscopes have recently been reported. Interim guidelines for mitigating endoscope-associated transmission have been proposed, but there has not been a systematic appraisal of CRE prevention practices. METHODS: We conducted a systematic review of endoscope-associated CRE infection episodes, abstracting information on outbreak detection, mitigation, outcomes, and corrective steps taken to prevent recurrence. RESULTS: Seven distinct outbreaks were identified in the published literature, and 5 of these were associated with duodenal endoscopy, with the remaining 2 associated with cystoscopy and ureteroscopy. Several investigators noted difficulties in cleaning protocols surrounding difficult to access components, such as the elevator on duodenoscopes. The published investigations did not report any failures of sterilization. It is unclear if routine reprocessing was ineffective, or difficult to execute properly. CONCLUSIONS: Meticulous cleaning protocols and increased surveillance are necessary to prevent and detect future outbreaks of CRE and to determine whether more stringent measures, such as sterilization, are needed for duodenoscopes. PMID- 27179398 TI - Management of gastric fold herniation after laparoscopic adjustable gastric banded plication: a single-center experience. AB - BACKGROUND: Laparoscopic adjustable gastric banded plication (LAGBP) is a novel bariatric procedure, and little is known about its potential complications. OBJECTIVES: Herein, we report on complications of LAGBP and discuss the clinical features and diagnostic and therapeutic strategies in such situations, with emphasis on gastric fold herniation (GFH). SETTING: University Hospital. METHODS: Prospectively collected data of 223 patients who underwent LAGBP for morbid obesity between August 2009 and December 2014 were retrospectively analyzed. Follow-up at 1 year was 75%. RESULTS: Eight patients (3.5%) required readmission due to major complications, including 1 trocar site hernia, 1 band leak, 1 gastric stenosis, and 5 GFHs. GFHs occurred mostly in the first postoperative month (4/5, 80%) and at the fundus (5/5, 100%); 4 GFHs occurred in the initial 70 patients. Seven laparoscopic reoperations were required for managing GFH. The gastric band was removed in 3 patients (of 5; 60%). Two patients developed residual intra-abdominal abscess and were treated successfully by image-guided drainage. In March 2012, we reversed the order of our surgical techniques for the subsequent 153 patients and performed greater curvature plication first, followed by band placement. Only one GFH occurred after this change in surgical order (1/153 versus 4/70; P< .05). CONCLUSIONS: High clinical suspicion assisted by radiological investigations and early surgical intervention is the key for managing GFH after LAGBP. Though GFH complications were rare, we significantly reduced its occurrence by altering the surgical order in LAGBP to plication followed by banding. PMID- 27179399 TI - Comment on: Technique or technology? Evaluating leaks after gastric bypass. PMID- 27179400 TI - Recommendations for the presurgical psychosocial evaluation of bariatric surgery patients. AB - Psychosocial factors have significant potential to affect long-term outcomes of bariatric surgery, including emotional adjustment, adherence to the recommended postoperative lifestyle regimen, weight loss outcomes, and co-morbidity improvement and or resolution. Thus, it is recommended that bariatric behavioral health clinicians with specialized knowledge and experience be involved in the evaluation and care of patients both before and after surgery. The evaluating clinician plays a number of important roles in the multidisciplinary treatment of the bariatric patient. Central among these is the role of identifying factors that may pose challenges to optimal surgical outcome and providing recommendations to the patient and bariatric team on how to address these issues. This document outlines recommendations for the psychosocial evaluation of bariatric surgery patients, appropriate qualifications of those conducting these evaluations, communication of evaluation results and suggested treatment plan, and the extension of behavioral healthcare of the bariatric patient to the entire span of the surgical and postsurgical process. PMID- 27179401 TI - Pathological complete remission and long-term outcome-what do we know in 2016? PMID- 27179403 TI - Corrigendum to 'Phosphorus, and nitrogen co-doped carbon dots as a fluorescent probe for real-time measurement of reactive oxygen and nitrogen species inside macrophages' [Biosens. Bioelectron. 79 (2016) 822-828]. PMID- 27179402 TI - 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial. AB - BACKGROUND: In the primary analysis of the NeoSphere trial, patients given neoadjuvant pertuzumab, trastuzumab, and docetaxel showed a significantly improved pathological complete response compared with those given trastuzumab and docetaxel after surgery. Here, we report 5-year progression-free survival, disease-free survival, and safety. METHODS: In this multicentre, open-label, phase 2 randomised trial in hospitals and medical clinics, treatment-naive adults with locally advanced, inflammatory, or early-stage HER2-positive breast cancer were randomly assigned (1:1:1:1) to receive four neoadjuvant cycles of trastuzumab (8 mg/kg loading dose, followed by 6 mg/kg every 3 weeks) plus docetaxel (75 mg/m(2) every 3 weeks, increasing to 100 mg/m(2) from cycle 2 if tolerated; group A), pertuzumab (840 mg loading dose, followed by 420 mg every 3 weeks) and trastuzumab plus docetaxel (group B), pertuzumab and trastuzumab (group C), or pertuzumab and docetaxel (group D). After surgery, patients received three cycles of FEC (fluorouracil 600 mg/m(2), epirubicin 90 mg/m(2), and cyclophosphamide 600 mg/m(2)) every 3 weeks (patients in group C received four cycles of docetaxel prior to FEC), and trastuzumab 6 mg/kg every 3 weeks to complete 1 year's treatment (17 cycles in total). Randomisation was done by a central centre using dynamic allocation, stratified by operable, locally advanced, and inflammatory breast cancer, and by oestrogen and/or progesterone receptor positivity. Safety analyses were done according to treatment received. The primary endpoint (pathological complete response) was previously reported; secondary endpoints reported here are 5-year progression-free survival (analysed in the intention-to-treat population) and disease-free survival (analysed in patients who had surgery). Secondary and exploratory analyses were not powered for formal statistical hypothesis testing, and therefore results are for descriptive purposes only. The study ended on Sept 22, 2014 (last patient, last visit). This study is registered with ClinicalTrials.gov, number NCT00545688. FINDINGS: Between Dec 17, 2007, and Dec 22, 2009, 417 eligible patients were randomly assigned to group A (107 patients), group B (107 patients), group C (107 patients), or group D (96 patients). One patient in group A withdrew before treatment. One patient assigned to group D received group A treatment, one patient assigned to group D received group B treatment, and one patient assigned to group B received group C treatment. At clinical cutoff, 87 patients had progressed or died. 5-year progression-free survival rates were 81% (95% CI 71 87) for group A, 86% (77-91) for group B, 73% (64-81) for group C, and 73% (63 81) for group D (hazard ratios 0.69 [95% CI 0.34-1.40] group B vs group A, 1.25 [0.68-2.30] group C vs group A, and 2.05 [1.07-3.93] group D vs group B). Disease free survival results were consistent with progression-free survival results and were 81% (95% CI 72-88) for group A, 84% (72-91) for group B, 80% (70-86) for group C, and 75% (64-83) for group D. Patients who achieved total pathological complete response (all groups combined) had longer progression-free survival compared with patients who did not (85% [76-91] in patients who achieved total pathological response vs 76% [71-81] in patients who did not achieve total pathological response; hazard ratio 0.54 [95% CI 0.29-1.00]). There were no new or long-term safety concerns and tolerability was similar across groups (neoadjuvant and adjuvant treatment periods combined). The most common grade 3 or worse adverse events were neutropenia (group A: 71 [66%] of 107 patients; group B: 59 [55%] of 107; group C: 40 [37%] of 108; group D: 60 [64%] of 94), febrile neutropenia (group A: 10 [9%]; group B: 12 [11%]; group C: 5 [5%]; group D: 15 [16%]), and leucopenia (group A: 13 [12%]; group B: 6 [6%]; group C: 4 [4%]; group D: 8 [9%]). The number of patients with one or more serious adverse event was similar across groups (19-22 serious adverse events per group in 18-22% of patients). INTERPRETATION: Progression-free survival and disease-free survival at 5-year follow-up show large and overlapping CIs, but support the primary endpoint (pathological complete response) and suggest that neoadjuvant pertuzumab is beneficial when combined with trastuzumab and docetaxel. Additionally, they suggest that total pathological complete response could be an early indicator of long-term outcome in early-stage HER2-positive breast cancer. FUNDING: F Hoffmann La Roche. PMID- 27179405 TI - [Human growth hormone and Turner syndrome]. AB - OBJECTIVE: The evaluation of clinical and analytical parameters as predictors of the final growth response in Turner syndrome patients treated with growth hormone. MATERIAL AND METHODS: A retrospective study was performed on 25 girls with Turner syndrome (17 treated with growth hormone), followed-up until adult height. Auxological, analytical, genetic and pharmacological parameters were collected. A descriptive and analytical study was conducted to evaluate short (12 months) and long term response to treatment with growth hormone. RESULTS: A favourable treatment response was shown during the first year of treatment in terms of height velocity gain in 66.6% of cases (height-gain velocity >3cm/year). A favourable long-term treatment response was also observed in terms of adult height, which increased by 42.82+/-21.23cm (1.25+/-0.76 SDS), with an adult height gain of 9.59+/-5.39cm (1.68+/-1.51 SDS). CONCLUSIONS: Predictors of good response to growth hormone treatment are: A) initial growth hormone dose, B) time on growth hormone treatment until starting oestrogen therapy, C) increased IGF1 and IGFBP-3 levels in the first year of treatment, and D) height gain velocity in the first year of treatment. PMID- 27179404 TI - Transarterial Chemoembolization Using Sorafenib in a Rabbit VX2 Liver Tumor Model: Pharmacokinetics and Antitumor Effect. AB - PURPOSE: To investigate feasibility, safety, and effect of transarterial chemoembolization using sorafenib on degree of tumor necrosis in a rabbit VX2 liver tumor model. MATERIALS AND METHODS: New Zealand White rabbits (n = 20) with a VX2 tumor were divided into two groups; one group was treated with hepatic arterial administration of 0.5 mL ethiodized oil alone (Lipiodol; Guerbet, Aulnay sous-Bois, France) (transarterial embolization with Lipiodol [TAE-L] group), and one group was treated with 0.5 mL ethiodized oil plus 10 mg sorafenib (transarterial embolization with sorafenib [TAE-S] group). Liquid chromatography tandem mass spectrometry was used to measure sorafenib concentration in peripheral blood and tissue. Hepatic enzymes, vascular endothelial growth factor (VEGF), and hypoxia-inducible factor 1alpha (HIF-1alpha) were measured at 0, 24, and 72 hours after treatment. Histopathologic examination was performed to evaluate extent of tumor necrosis and normal parenchymal damage. RESULTS: Serum sorafenib concentration peaked at 2 hours after treatment. The mean tissue concentration was 406.8 times greater than the serum concentration. Aspartate aminotransferase and alanine aminotransferase levels were significantly elevated in the TAE-S group at 24 hours after treatment. Serum VEGF and HIF-1alpha concentrations were not significantly different between the TAE-L and TAE-S groups. Hepatic parenchymal damage was more severe in the TAE-S group. Mean fraction of tumor necrosis after treatment was significantly greater in the TAE-S group. CONCLUSIONS: Transarterial chemoembolization using sorafenib resulted in a high intrahepatic concentration of sorafenib. The degree of tumor necrosis was significantly greater in the TAE-S group compared with the TAE-L group, but more severe toxicity of normal liver tissue also occurred. PMID- 27179406 TI - DOPC-DOPE composition dependent Lalpha-HII thermotropic phase transition: SAXD study. AB - The structural polymorphism and parameters of lyotropic phases formed in the mixed dioleoylphosphatidylcholine-dioleoylphosphatidylethanolamine (DOPC-DOPE) system upon heating and varying DOPC:DOPE composition were studied by means of small-angle X-ray diffraction (SAXD). In the temperature range 5-80 degrees C a sequence of fluid lamellar Lalpha - inverse hexagonal HII - inverse cubic QII phases was detected at DOPE mole fractions XDOPE>=0.65. A superposition of two bicontinuous cubic QII phases of Pn3m and Ia3d space groups was identified. The Lalpha to HII phase transition temperature, the onset of the QII phase formation, as well as the lattice spacings of the Lalpha and HII phases were found to decrease with rising DOPE content. Moreover, evidence of structural rearrangement during the Lalpha to HII phase transition is given and change of transition mechanism with varying XDOPE is suggested. PMID- 27179408 TI - The cross-sectional relationships of dietary and serum vitamin D with cardiometabolic risk factors: Metabolic components, subclinical atherosclerosis, and arterial stiffness. AB - OBJECTIVE: There has been increasing interest in non-skeletal interactions between vitamin D insufficiency, which is common, and cardiovascular event and cardiovascular disease (CVD) risk factors. METHODS: To evaluate cross-sectional associations between dietary and serum vitamin D status and metabolic abnormalities and arterial changes among 1054 adults aged >=40 y (404 men and 650 women) in a rural area of South Korea. Study subjects were divided into three groups according to dietary vitamin D intake (tertiles) measured by food frequency questionnaire and serum 25(OH)D levels (<=20, 21-29, and >=30 ng/mL). Metabolic components (blood pressure, lipid profiles, and glycemic index) and arterial changes (brachial ankle pulse wave velocity [baPWV] and carotid artery intima-media wall thickness [cIMT]) were measured. RESULTS: Dietary vitamin D was inversely associated with diastolic blood pressure (DBP) and baPWV among men, but the association disappeared after multinutrient supplement users were excluded. Among women, there was an inverse association between dietary vitamin D and triacylglycerol (TG) levels. However, serum 25(OH)D showed a significant positive relationship with HDL cholesterol in both men and women, while a positive linear trend or nonlinear trend with serum 25(OH)D levels was shown in TG levels among men and in systolic blood pressure (SBP), DBP, total cholesterol, and baPWV among women. The positive relationship between serum 25(OH)D with baPWV disappeared after adjustment for blood pressure. CONCLUSIONS: Serum 25(OH)D may be favorably related to HDL cholesterol. However, serum 25(OH)D may not favorably related to subclinical atherosclerosis and arterial stiffness measured by cIMT and baPWV. The positive relationship between 25(OH)D and baPWV is likely to be mediated by blood pressure. PMID- 27179409 TI - In vitro screening of silver nanoparticles and ionic silver using neural networks yields differential effects on spontaneous activity and pharmacological responses. AB - Silver nanoparticles (AgNPs) are used in a wide range of consumer and medical products because of their antimicrobial and antifungal properties, and can translocate to the brain following exposure. Therefore, to screen AgNPs for potential impacts on human health, it is essential to examine neural function. The present study examined AgNPs (3 citrate coated, 3 PVP coated; 10-75nm) and AgNO3 effects on spontaneous and pharmacologically-induced neural network function in rat primary cortical cells on multi-well microelectrode array (mwMEA) plates. Baseline activity (1h) was recorded prior to exposure to non-cytotoxic concentrations of AgNPs and AgNO3 (0.08-0.63 and 0.08-1.7MUg/ml, respectively). Changes in number of total extracellularly-recorded action potential spikes (total spikes; TS) and active electrodes (AE), relative to controls, were assessed 1, 24, and 48h after exposure to AgNP suspensions or AgNO3. After the 48h recording, the response to a pharmacological challenge with the GABAA antagonist, bicuculline (BIC), was assessed. Only two particles altered neural network function. Citrate coated 10nm AgNP caused concentration-related increases in AEs at 24h. After BIC treatment, PVP coated 75nm AgNP caused concentration dependent increases in AE. AgNO3 effects differed from AgNPs, causing a concentration-related decrease in AEs at 24 and 48h, and a concentration-related decrease in TS following BIC challenge. Importantly, the direction of AgNO3 effects on neural activity was opposite those of 10nm Ag citrate at concentrations up to 0.63MUg/ml, and different from 75nm Ag PVP, indicating ionic silver does not mediate these effects. These results demonstrate that non cytotoxic concentrations of 10nm citrate- and 75nm PVP-coated Ag NPs alter neural network function in vitro, and should be considered for additional neurotoxicity hazard characterization. PMID- 27179407 TI - The role of cholesterol in membrane fusion. AB - Cholesterol modulates the bilayer structure of biological membranes in multiple ways. It changes the fluidity, thickness, compressibility, water penetration and intrinsic curvature of lipid bilayers. In multi-component lipid mixtures, cholesterol induces phase separations, partitions selectively between different coexisting lipid phases, and causes integral membrane proteins to respond by changing conformation or redistribution in the membrane. But, which of these often overlapping properties are important for membrane fusion?-Here we review a range of recent experiments that elucidate the multiple roles that cholesterol plays in SNARE-mediated and viral envelope glycoprotein-mediated membrane fusion. PMID- 27179410 TI - MicroRNA let-7b induces lens epithelial cell apoptosis by targeting leucine-rich repeat containing G protein-coupled receptor 4 (Lgr4) in age-related cataract. AB - Owing to a rapidly aging population, vision impairment caused by age-related cataract has become very common. Age-related cataract has also become one of the principal causes of blindness, and apoptosis of lens epithelial cells contributes to non-congenital cataract development. Previous studies have reported that microRNA let-7b (let-7b) is upregulated in cataractous lens epithelial cells, and the expression level of let-7b is positively associated with N, C and P cataract scores. However, the role of let-7b in the development of age-related cataract remains unclear. Here, we observed that the expression level of let-7b in the anterior lens capsules of age-related cataract was significantly higher than that in the normal anterior lens capsules. We performed ultraviolet (UV) irradiation to induce lens epithelial cell apoptosis. The results showed that the expression level of let-7b in lens epithelial cells which were treated by UV irradiation was significantly higher than that in the control, and let-7b promoted UV irradiation induced apoptosis. Furthermore, we showed that leucine-rich repeat containing G protein-coupled receptor 4 (Lgr4) was a direct target of let-7b, and let-7b modulated lens epithelial cell apoptosis by directly targeting Lgr4. These findings will offer new insights into our understanding of the molecular mechanisms underlying the pathogenesis of cataract. PMID- 27179412 TI - First insights into the expression of VAX2 in humans and its localization in the adult primate retina. AB - VAX2 is a transcription factor specifically expressed in the ventral region of the prospective neural retina in vertebrates and is required for ventral eye specification. Despite its extensive analysis in vertebrates, the biological role of VAX2 in the human is presently unclear. This study was undertaken to investigate VAX2 in humans aiming to gain new knowledge into its involvement in retinal function. Here, we report VAX2 gene expression and protein localization in cultured cells and adult retina. RT-PCR experiments indicated that VAX2 is enriched in neuronal tissues. Moreover, we identified a novel isoform most abundantly expressed in the retina. We termed the known transcript (NM_012476) isoform-1, and the newly identified transcript as isoform-2. Analysis of protein localization in cultured cells revealed that isoform-1 localizes to the nucleus and isoform-2 is widely expressed within the cell; partial co-localization of isoform-2 and actin filaments was also observed. In nonhuman primate retina VAX2 was seen either in the nuclear or in the cytoplasmic compartment depending on the retinal cell type. In addition, a noteworthy enrichment of the signal was observed in the outer segment of cone photoreceptors. Overall, this study provides the first insights into the expression of VAX2 in humans and its localization in the adult primate retina. Moreover, preliminary characterization of alternative variants suggests an involvement of VAX2 in multiple cellular pathways. Our findings raise the interesting possibility for further investigation of VAX2 in the retina in health and disease. PMID- 27179413 TI - Obstructive lung diseases and beta-blockers: Where do we stand? PMID- 27179411 TI - Toward in vivo two-photon analysis of mouse aqueous outflow structure and function. AB - The promise of revolutionary insights into intraocular pressure (IOP) and aqueous humor outflow homeostasis, IOP pathogenesis, and novel therapy offered by engineered mouse models has been hindered by a lack of appropriate tools for studying the aqueous drainage tissues in their original 3-dimensional (3D) environment. Advances in 2-photon excitation fluorescence imaging (TPEF) combined with availability of modalities such as transgenic reporter mice and intravital dyes have placed us on the cusp of unlocking the potential of the mouse model for unearthing insights into aqueous drainage structure and function. Multimodality 2 photon imaging permits high-resolution visualization not only of tissue structural organization but also cells and cellular function. It is possible to dig deeper into understanding the cellular basis of aqueous outflow regulation as the technique integrates analysis of tissue structure, cell biology and physiology in a way that could also lead to fresh insights into human glaucoma. We outline recent novel applications of two-photon imaging to analyze the mouse conventional drainage system in vivo or in whole tissues: (1) collagen second harmonic generation (SHG) identifies the locations of episcleral vessels, intrascleral plexuses, collector channels, and Schlemm's canal in the distal aqueous drainage tract; (2) the prospero homeobox protein 1-green fluorescent protein (GFP) reporter helps locate the inner wall of Schlemm's canal; (3) Calcein AM, siGLOTM, the fluorescent reporters m-Tomato and GFP, and coherent anti-Stokes scattering (CARS), are adjuncts to TPEF to identify live cells by their membrane or cytosolic locations; (4) autofluorescence and sulforhodamine-B to identify elastic fibers in the living eye. These tools greatly expand our options for analyzing physiological and pathological processes in the aqueous drainage tissues of live mice as a model of the analogous human system. PMID- 27179414 TI - Zika virus in saliva-New challenges for prevention of human to human transmission. PMID- 27179415 TI - Watch out for diabetes: Less education but let's get moving, let's eat less! PMID- 27179416 TI - Obesity or smoking: Which factor contributes more to the incidence of myocardial infarction? PMID- 27179417 TI - The cellular lipid landscape. PMID- 27179418 TI - Reversible oxidation controls the activity and oligomeric state of the mammalian phosphoglycolate phosphatase AUM. AB - Redox-dependent switches of enzyme activity are emerging as important fine-tuning mechanisms in cell signaling. For example, protein tyrosine phosphatases employ a conserved cysteine residue for catalysis, which also renders them highly susceptible to reversible inactivation by oxidation. In contrast, haloacid dehalogenase (HAD)-type phosphatases perform catalysis via a phosphoaspartyltransferase reaction. The potential regulation of HAD phosphatases by reversible oxidation has not yet been explored. Here, we investigate the redox sensitivity of the HAD-type phosphoglycolate phosphatase PGP, also known as AUM or glycerol-3-phosphate phosphatase. We show that recombinant, purified murine PGP is inhibited by oxidation and re-activated by reduction. We identify three reactive cysteine residues in the catalytic core domain of PGP (Cys35, Cys104 and Cys243) that mediate the reversible inhibition of PGP activity and the associated, redox-dependent conformational changes. Structural analysis suggests that Cys35 oxidation weakens van-der-Waals interactions with Thr67, a conserved catalytic residue required for substrate coordination. Cys104 and Cys243 form a redox-dependent disulfide bridge between the PGP catalytic core and cap domains, which may impair the open/close-dynamics of the catalytic cycle. In addition, we demonstrate that Cys297 in the PGP cap domain is essential for redox-dependent PGP oligomerization, and that PGP oxidation/oligomerization occurs in response to stimulation of cells with EGF. Finally, employing a modified cysteinyl-labeling assay, we show that cysteines of cellular PGP are transiently oxidized to sulfenic acids. Taken together, our findings establish that PGP, an aspartate dependent HAD phosphatase, is transiently inactivated by reversible oxidation in cells. PMID- 27179419 TI - Vipera lebetina venom nucleases. AB - Nucleases, in particular ribo- and deoxyribonucleases, are among the least studied snake venom enzymes. In the present study we have partially purified different nucleases from Vipera lebetina venom. The DNase activity has been proved by DNA degradation both in solution as well as in-gel (zymogram-method). In DNA-containing SDS-PAGE V. lebetina venom exhibits DNA-degrading activity in bands with molecular masses of ~120, 30-35 and 22-25 kDa. The 120 kDa band corresponds to phosphodiesterase, a 3', 5'-exonuclease. The endonucleolytic activity of the lower-molecular-mass protein has been confirmed by plasmid degradation and the visualization of the results in agarose gel (with ethidium bromide) electrophoresis. A partial DNA sequence of putative RNase H1 has been determined from the V. lebetina venom gland cDNA library. The translated sequence is similar to the assumed RNase H1 from Crotalus adamanteus (AFJ51163). The RNA/DNA hybrid is hydrolysed by V. lebetina venom and venom fractions. The masses of tryptic peptides from the SDS-PAGE 30-35 kDa band are in concordance with the theoretical peptide masses from the respective translated sequence. For the first time RNase H1-like enzyme activity has been ascertained in snake venom, and sequencing a relevant partial transcript confirmed the identification of this enzyme. PMID- 27179421 TI - Exploiting the antithrombotic effect of the (pro)thrombin inhibitor bothrojaracin. AB - Bothrojaracin is a 27 kDa C-type lectin-like protein from Bothrops jararaca snake venom. It behaves as a potent thrombin inhibitor upon high-affinity binding to thrombin exosites. Bothrojaracin also forms a stable complex with prothrombin that can be detected in human plasma. Formation of the zymogen-inhibitor complex severely decreases prothrombin activation and contributes to the anticoagulant activity of bothrojaracin. In the present study, we employed two rodent models to evaluate the antithrombotic effect of bothrojaracin in vivo: stasis-induced thrombosis and thrombin-induced pulmonary thromboembolism. It was observed that bothrojaracin interacts with rat prothrombin in plasma. Ex-vivo assays showed stable complex formation even after 24 h of a single bothrojaracin dose. As a result, bothrojaracin showed significant antithrombotic activity in a rat venous thrombosis model elicited by thromboplastin combined with stasis. The antithrombotic activity of bothrojaracin (1 mg/kg) persisted for up to 24 h and it was associated with moderate bleeding as assessed by a tail transection method. Formation of bothrojaracin-prothrombin complex has been also observed following intravenous administration of the inhibitor into mice. As a result, bothrojaracin effectively protected mice from thrombin-induced fatal thromboembolism. We conclude that bothrojaracin is a potent antithrombotic agent in vivo and may serve as a prototype for the development of new zymogen-directed drugs that could result in prolonged half-life and possible decreased hemorrhagic risk. PMID- 27179420 TI - Functional characterizations of venom phenotypes in the eastern diamondback rattlesnake (Crotalus adamanteus) and evidence for expression-driven divergence in toxic activities among populations. AB - Phenotypes frequently vary across and within species. The connection between specific phenotypic effects and function, however, is less understood despite being essential to our understanding of the adaptive process. Snake venoms are ideal for identifying functionally important phenotypic variation because venom variation is common, and venoms can be functionally characterized through simple assays and toxicity measurements. Previous work with the eastern diamondback rattlesnake (Crotalus adamanteus) used multivariate statistical approaches to identify six unique venom phenotypes. We functionally characterized hemolytic, gelatinase, fibrinogenolytic, and coagulant activity for all six phenotypes, as well as one additional venom, to determine if the statistically significant differences in toxin expression levels previously documented corresponded to differences in venom activity. In general, statistical differences in toxin expression predicted the identified functional differences, or lack thereof, in toxic activity, demonstrating that the statistical approach used to characterize C. adamanteus venoms was a fair representation of biologically meaningful differences. Minor differences in activity not accounted for by the statistical model may be the result of amino-acid differences and/or post-translational modifications, but overall we were able to link variation in protein expression levels to variation in function as predicted by multivariate statistical approaches. PMID- 27179422 TI - Inhibition of the superantigenic activities of Staphylococcal enterotoxin A by an aptamer antagonist. AB - Staphylococcal enterotoxin A (SEA) is an important component of Staphylococcus aureus pathogenesis. SEA induces T lymphocytes activation and proliferation, resulting in the release of a large number of inflammatory cytokines. Blocking the toxic cascade triggered by SEA may be an effective strategy for the treatment of SEA-induced diseases. Through a systematic evolution of ligands by exponential enrichment process, we obtained an aptamer (S3) that could bind SEA with both high affinity and specificity, with a Kd value 36.93 +/- 7.29 nM (n = 3). This aptamer antagonist effectively inhibited SEA-mediated human peripheral blood mononuclear cells proliferation and inflammatory cytokines (IFN-gamma, TNF-alpha, IL-2 and IL-6) secretion. Moreover, PEGylated S3 significantly reduced mortality in murine lethal toxic shock models established by lipopolysaccharide-potentiated SEA. Therefore, this novel aptamer antagonist has the potential to become a new strategy for treating S. aureus infections and SEA-induced diseases. PMID- 27179423 TI - 3D photography is a reliable method of measuring infantile haemangioma volume over time. AB - BACKGROUND: Infantile haemangiomas are common lesions of infancy. With the development of novel treatments utilised to accelerate their regression, there is a need for a method of assessing these lesions over time. Volume is an ideal assessment method because of its quantifiable nature. This study investigated whether 3D photography is a valid tool for measuring the volume of infantile haemangiomas over time. METHOD: Thirteen children with infantile haemangiomas presenting to the Vascular Anomalies Clinic, Royal Children's Hospital/Lady Cilento Children's Hospital treated with propranolol were included in the study. Lesion volume was assessed using 3D photography at presentation, one month and three months follow up. Intrarater reliability was determined by retracing all images several months after the initial mapping. Interrater reliability of the 3D camera software was determined by two investigators, blinded to each other's results, independently assessing infantile haemangioma volume. RESULTS: Lesion volume decreased significantly between presentation and three-month follow-up (p<0.001). Volume intra- and interrater reliability were excellent with ICC 0.991 (95% CI 0.982, 0.995) and 0.978 (95% CI 0.955, 0.989), respectively. CONCLUSION: This study demonstrates images taken with the 3D LifeVizTM camera and lesion volume calculated with Dermapix(r) software is a reliable method for assessing infantile haemangioma volume over time. PMID- 27179424 TI - Zika Virus Disrupts Neural Progenitor Development and Leads to Microcephaly in Mice. AB - The link between Zika virus (ZIKV) infection and microcephaly has raised urgent global alarm. The historical African ZIKV MR766 was recently shown to infect cultured human neural precursor cells (NPCs), but unlike the contemporary ZIKV strains, it is not believed to cause microcephaly. Here we investigated whether the Asian ZIKV strain SZ01 could infect NPCs in vivo and affect brain development. We found that SZ01 replicates efficiently in embryonic mouse brain by directly targeting different neuronal linages. ZIKV infection leads to cell cycle arrest, apoptosis, and inhibition of NPC differentiation, resulting in cortical thinning and microcephaly. Global gene expression analysis of infected brains reveals upregulation of candidate flavirus entry receptors and dysregulation of genes associated with immune response, apoptosis, and microcephaly. Our model provides evidence for a direct link between Zika virus infection and microcephaly, with potential for further exploration of the underlying mechanisms and management of ZIKV-related pathological effects during brain development. PMID- 27179425 TI - Ability of Lactobacillus plantarum lipoteichoic acid to inhibit Vibrio anguillarum-induced inflammation and apoptosis in silvery pomfret (Pampus argenteus) intestinal epithelial cells. AB - Lipoteichoic acid (LTA) is a major constituent of the cell wall of Gram-positive bacteria. The structure and immunomodulation of LTA vary greatly between different species. LTA from Lactobacillus plantarum has been shown to exert anti pathogenic effects. Vibrio anguillarum is a major causative agent of vibriosis, one of the most prevalent fish diseases. The purpose of this study was to examine the effects of L. plantarum LTA on V. anguillarum growth, adhesion, and induced inflammation and apoptosis in intestinal epithelial cells of silvery pomfret (Pampus argenteus). Our results showed that L. plantarum LTA was unable to inhibit V. anguillarum growth; however, it significantly inhibited adhesion of V. anguillarum. It also showed significant inhibitory effects on EHEC-induced inflammation and apoptosis by modulating the expression of NF-kappaB (nuclear factor kappa B), IkappaB (inhibitor of NF-kappaB), Bcl2 (B-cell leukemia/lymphoma 2), BAX (Bcl-2-associated X protein), IL-8 (interleukin 8) and TNF-alpha (tumor necrosis factor-alpha), and via inhibition of caspase-9 and caspase-3 activation. These data extend our understanding of the beneficial effects of L. plantarum LTA, which is related to the inhibition of V. anguillarum, and suggest that L. plantarum LTA has potential as a new therapeutic agent against V. anguillarum caused vibriosis in fish. PMID- 27179426 TI - Mitigation of tight junction protein dysfunction in lung microvascular endothelial cells with pitavastatin. AB - BACKGROUND: Statin use in individuals with chronic obstructive pulmonary disease (COPD) with coexisting cardiovascular disease is associated with a reduced risk of exacerbations. The mechanisms by which statin plays a role in the pathophysiology of COPD have not been defined. To explore the mechanisms involved, we investigated the effect of statin on endothelial cell function, especially endothelial cell tight junctions. METHOD: We primarily assessed whether pitavastatin could help mitigate the development of emphysema induced by continuous cigarette smoking (CS) exposure. We also investigated the activation of liver kinase B1 (LKB1)/AMP-activated protein kinase (AMPK) signaling, which plays a role in maintaining endothelial functions, important tight junction proteins, zonula occludens (ZO)-1 and claudin-5 expression, and lung microvascular endothelial cell permeability. RESULTS: We found that pitavastatin prevented the CS-induced decrease in angiomotin-like protein 1 (AmotL1)-positive vessels via the activation of LKB1/AMPK signaling and IFN-gamma-induced hyperpermeability of cultured human lung microvascular endothelial cells by maintaining the levels of AmotL1, ZO-1, and claudin-5 expression at the tight junctions. CONCLUSION: Our results indicate that the maintenance of lung microvascular endothelial cells by pitavastatin prevents tight junction protein dysfunctions induced by CS. These findings may ultimately lead to new and novel therapeutic targets for patients with COPD. PMID- 27179427 TI - Perfluoroalkylated substances in edible livers of farm animals, including depuration behaviour in young sheep fed with contaminated grass. AB - Perfluoroalkylated substances (PFASs) present a potential health risk for consumers. In animals these compounds are known to accumulate in livers. In order to determine potential PFASs contamination in commercially available livers, samples from farmed sheep, horses, cows, pigs and chicken were collected from the Dutch market. PFOS was the only detectable PFAS and its concentration was higher in free ranging animals like cows and sheep. The detected levels of PFOS in the liver samples were very low (up to 4.5 ng g(-1) ww). To further study the kinetic behaviour in foraging animals, samples from a study in which sheep were fed with grass obtained from a river floodplain, were examined. PFOS was the only detectable PFAS in the contaminated grass pellets, showing a level of about 0.5 MUg kg(-1). Young blackhead sheep were fed with either clean or contaminated grass for a period up to 112 days. A time-dependent increase in liver PFOS concentrations was observed from 2.4 to 10.9 ng g(-1) ww after 8 and 112 days respectively. A time-dependent depuration was observed in livers of animals switched to clean grass after 56 days of exposure, from 9.2 to 4.7 ng g(-1) ww after 64 and 112 days respectively. The percentage of PFOS ingested from the grass and retained in the liver was estimated to be 12% at day 56, and decreased gradually to 6% after 56 days on clean grass, showing that the decrease in levels is not only caused by an increase in liver weight. Levels detected in commercial livers but also those in the sheep study would not lead to exceedance of the current TDI for PFOS set by EFSA. Therefore, it can be assumed that they do not present a risk for human health. PMID- 27179428 TI - Effects of reclaimed water matrix on fate of pharmaceuticals and personal care products in soil. AB - Reclaimed water is increasingly used to supplement water resources. However, reclaimed water has a complex matrix, which includes emerging chemical contaminants, that is introduced to the soil when this water is used for irrigation. The effects of microbial activity, dissolved matter, nutrients, and particulate matter in reclaimed water on half-life of 11 pharmaceutical and personal care products (PPCPs) in soil were investigated with 7 treatment waters, namely swine lagoon effluent (either unaltered, sterilized, or filtered and sterilized) and nanopure water (either unaltered or with added nitrogen, phosphorus, or potassium). The extractable residues of the parent PPCPs were measured over 35 d. Lagoon microbial activity was significantly (p <= 0.05) related to increased half-life of 4 PPCPs (carbamazepine, fluoxetine, ibuprofen, sulfamethoxazole) by 14-74%, and to decreased half-life of 3 others (caffeine, gemfibrozil, naproxen) by 13-25%. The presence of lagoon dissolved matter was significantly correlated with a 20-110% increase in half-life for 6 PPCPs (caffeine, estrone, gemfibrozil, ibuprofen, naproxen, triclocarban). However, lagoon particulate matter was significantly correlated with 9-52% decrease in half-life for these same compounds, as well as trimethoprim. The levels of nitrogen, phosphorous, and potassium in the lagoon effluent were not significantly related to half-life for most PPCPs, except caffeine. Overall, specific components of reclaimed water matrix had different effects on the soil half-lives of PPCPs, suggesting that the composition of reclaimed water needs to be considered when evaluating PPCP fate after land application. PMID- 27179429 TI - Bromine and bromide content in soils: Analytical approach from total reflection X ray fluorescence spectrometry. AB - Monitoring total bromine and bromide concentrations in soils is significant in many environmental studies. Thus fast analytical methodologies that entail simple sample preparation and low-cost analyses are desired. In the present work, the possibilities and drawbacks of low-power total reflection X-ray fluorescence spectrometry (TXRF) for the determination of total bromine and bromide contents in soils were evaluated. The direct analysis of a solid suspension using 20 mg of fine ground soil (<63 MUm) gave a 3.7 mg kg(-1) limit of detection for bromine which, in most cases, was suitable for monitoring total bromine content in soils (Br content range in soils = 5-40 mg kg(-1)). Information about bromide determination in soils is also possible by analyzing the Br content in water soil extracts. In this case, the TXRF analysis can be directly performed by depositing 10 MUL of the internal standardized soil extract sample on a quartz glass reflector in a measuring time of 1500 s. The bromide limit of detection by this approach was 10 MUg L(-1). Good agreement was obtained between the TXRF results for the total bromine and bromide determinations in soils and those obtained by other popular analytical techniques, e.g. energy dispersive X-ray fluorescence spectrometry (total bromine) and ionic chromatography (bromide). As a study case, the TXRF method was applied to study bromine accumulation in two agricultural soils fumigated with a methyl bromide pesticide and irrigated with regenerated waste water. PMID- 27179430 TI - Use of hybrid composite particles prepared using alkoxysilane-functionalized amphiphilic polymer precursors for simultaneous removal of various pollutants from water. AB - In this study, we present new inorganic-organic hybrid particles and their possible application as an adsorbent for simultaneous removal of hydrophobic and hydrophilic pollutants from water. These hybrid particles were prepared using tailor-made alkoxysilane-functionalized amphiphilic polymer precursors (M-APAS), which have amphiphilic polymers and reactive alkoxysilane groups attached to the same backbone. Through a single conventional sol-gel process, the polymerization of M-APAS and the chemical conjugation of M-APAS onto silica nanoparticles was simultaneous, resulting in the formation of hybrid particles (M-APAS-SiO2) comprised of hyperbranch-like amphiphilic polymers bonded onto silica nanoparticles with a relatively high grafting efficiency. A test for the adsorption of water-soluble dye (organe-16) and water insoluble dye (solvent blue 35) onto the hybrid particles was performed to evaluate the possibility of adsorbing hydrophilic and hydrophobic compound within the same particle. The hybrid particle was also evaluated as an adsorbent for the removal of contaminated water containing various pollutants by wastewater treatment test. The hybrid particle could remove phenolic compounds from wastewater and the azo dye reactive orange-16 from aqueous solutions, and it was easily separated from the treated wastewater because of the different densities involved. These results demonstrate that the hybrid particles are a promising sorbent for hydrophilic and/or hydrophobic pollutants in water. PMID- 27179431 TI - Time-dependency of mice lung recovery after a 4-week exposure to traffic or biomass air pollutants. AB - The time-dependency of lung recovery after 3 intranasal instillations per week during four weeks of distilled water (C groups) or particles (15MUg) from traffic (U groups) or biomass burning (B groups) was observed in BALB/c mice. Lung mechanics [static elastance (Est), viscoelastic component of elastance (DeltaE), lung resistive (DeltaP1) and viscoelastic/inhomogeneous (DeltaP2) pressures] and histology were analyzed 1 (C1, U1, B1), 2 (C2, U2, B2), 7 (C7, U7, B7) or 14 days (C14, U14, B14) after the last instillation. Est, DeltaE, DeltaP1 and DeltaP2 were higher in U1 and B1 than in C1, returning to control values at day 2, except for DeltaP1 that normalized after 7 days. Alveolar collapse, bronchoconstriction index and alveolar lesion were larger in U1 and B1 than in C1, however collapse returned to baseline at 7 days, while the others normalized in 2 days. A 4-week exposure to U and B induced lung impairment that resolved 7 days after the last exposure. PMID- 27179432 TI - One-step synthesis, biodegradation and biocompatibility of polyesters based on the metabolic synthon, dihydroxyacetone. AB - The one-step synthesis of a polyester family containing dihydroxyacetone is described along with a quantitative analysis of in vitro/in vivo degradation kinetics and initial biocompatibility. Polyesters were synthesized by combining dihydroxyacetone, which is a diol found in the eukaryotic glucose metabolic pathway, with even-carbon aliphatic diacids (adipic, suberic, sebacic) represented in the long-chain alpha carboxylic acid metabolic pathway, by Schotten-Baumann acylation. We show that by using a crystalline monomeric form of dihydroxyacetone, well-defined polyesters can be formed in one step without protection and deprotection strategies. Both diacid length and polyester molecular weight were varied to influence polymer physical and thermal properties. Polyesters were generated with number-averaged (Mn) molecular weights ranging from 2200-11,500. Polydispersities were consistent with step-growth polymerization and ranged from 2 to 2.6. The melting (Tm) and recrystallization (Tc) temperatures were impacted in an unpredictable manner. Thermal transitions for the polyesters were highest for the adipic acid followed by suberic acid and sebacic acid, respectively. It was shown that the thermal response of the DHA based polyesters was influenced by both the diacid length and molecular weight. In vitro degradation studies revealed first-order weight loss kinetics, the molecular weight loss followed first order kinetics with 25%-40% of the original mass remaining after 8 weeks. In vivo testing over 16 weeks highlighted that mass loss ranged from ~70% to ~6% depending upon initial molecular weight and diacid length. Histological analysis revealed rapid resolution of both acute and chronic inflammatory responses, normal foreign body responses were observed and no inflammation was present after week 4. This one-step synthesis proved robust with unique copolymers warranting further study as potential biomaterials. PMID- 27179434 TI - Myocardial commitment from human pluripotent stem cells: Rapid production of human heart grafts. AB - Genome editing on human pluripotent stem cells (hPSCs) together with the development of protocols for organ decellularization opens the door to the generation of autologous bioartificial hearts. Here we sought to generate for the first time a fluorescent reporter human embryonic stem cell (hESC) line by means of Transcription activator-like effector nucleases (TALENs) to efficiently produce cardiomyocyte-like cells (CLCs) from hPSCs and repopulate decellularized human heart ventricles for heart engineering. In our hands, targeting myosin heavy chain locus (MYH6) with mCherry fluorescent reporter by TALEN technology in hESCs did not alter major pluripotent-related features, and allowed for the definition of a robust protocol for CLCs production also from human induced pluripotent stem cells (hiPSCs) in 14 days. hPSCs-derived CLCs (hPSCs-CLCs) were next used to recellularize acellular cardiac scaffolds. Electrophysiological responses encountered when hPSCs-CLCs were cultured on ventricular decellularized extracellular matrix (vdECM) correlated with significant increases in the levels of expression of different ion channels determinant for calcium homeostasis and heart contractile function. Overall, the approach described here allows for the rapid generation of human cardiac grafts from hPSCs, in a total of 24 days, providing a suitable platform for cardiac engineering and disease modeling in the human setting. PMID- 27179435 TI - Pitfalls and novel applications of particle sizing by dynamic light scattering. AB - After briefly introducing the theoretical equations for DLS based particle size analysis, the need for angular dependent DLS investigations is emphasized to obtain correct particle sizes. Practical examples are given that demonstrate the possible magnitudes of errors in particle size if DLS is measured at one large scattering angle, only, as done by essentially all, most frequently utilized commercial "single angle" particle sizers. The second part is focused on a novel DLS application to sensitively trace (nano)particle interactions with concentrated blood serum or plasma that leads to the formation of large aggregates in a size regime of ?100 nm. Most likely, such aggregates originate from protein induced bridging of nanoparticles, since it is well known that serum proteins adsorb onto the surface of essentially all nanoparticles utilized in medical applications. Thus, the protein corona around nanoparticles does not only change their biological identity but to a large extend also their size, thus possibly affecting biodistribution and in vivo circulation time. PMID- 27179433 TI - In vivo fate tracking of degradable nanoparticles for lung gene transfer using PET and Cerenkov imaging. AB - Nanoparticles (NPs) play expanding roles in biomedical applications including imaging and therapy, however, their long-term fate and clearance profiles have yet to be fully characterized in vivo. NP delivery via the airway is particularly challenging, as the clearance may be inefficient and lung immune responses complex. Thus, specific material design is required for cargo delivery and quantitative, noninvasive methods are needed to characterize NP pharmacokinetics. Here, biocompatible poly(acrylamidoethylamine)-b-poly(dl-lactide) block copolymer based degradable, cationic, shell-cross-linked knedel-like NPs (Dg-cSCKs) were employed to transfect plasmid DNA. Radioactive and optical beacons were attached to monitor biodistribution and imaging. The preferential release of cargo in acidic conditions provided enhanced transfection efficiency compared to non degradable counterparts. In vivo gene transfer to the lung was correlated with NP pharmacokinetics by radiolabeling Dg-cSCKs and performing quantitative biodistribution with parallel positron emission tomography and Cerenkov imaging. Quantitation of imaging over 14 days corresponded with the pharmacokinetics of NP movement from the lung to gastrointestinal and renal routes, consistent with predicted degradation and excretion. This ability to noninvasively and accurately track NP fate highlights the advantage of incorporating multifunctionality into particle design. PMID- 27179436 TI - Ceria/POMs hybrid nanoparticles as a mimicking metallopeptidase for treatment of neurotoxicity of amyloid-beta peptide. AB - Protein misfolding to amyloid aggregates is the hallmark for neurodegenerative disease. While much attention has been paid to screen natural proteases that can degrade amyloid-beta peptides (Abeta), it is difficult to apply them in the clinics with the intractable problem of immunogenicity in living organisms. Herein, we rationally designed an artificial nanozyme, Ceria/Polyoxometalates hybrid (CeONP@POMs) with both proteolytic and superoxide dismutase (SOD) activities. Our results indicated that CeONP@POMs could efficiently degrade Abeta aggregates and reduce intracellular reactive oxygen species (ROS). More importantly, CeONP@POMD could not only promote PC12 cell proliferation and can cross blood-brain barrier (BBB), but also inhibit Abeta-induced BV2 microglial cell activation which was demonstrated by immunoluorescence assay and flow cytometry measurements. In vivo studies further indicated that CeONP@POMD as nanozyme possessed good biocompatibility, evidenced by a detailed study of their biodistribution, body weight change, and in vivo toxicology. Therefore, our results pave the way for design of multifunctional artificial nanozyme for treatment of neurotoxicity of amyloid-beta peptide. PMID- 27179438 TI - Simplified extraction of bisphenols from bacterial culture suspensions and solid matrices. AB - We demonstrate the utility of a simple and fast methanol extraction method that achieves similar bisphenols recovery efficiencies from microbial culture suspensions and sediment material than more laborious and costly extraction procedures. The methanol extraction method may have broad application for the rapid analysis of hydrophobic compounds in biodegradation studies. PMID- 27179437 TI - Unfolded protein response-related gene regulation in inflamed periodontal tissues with and without Russell bodies. AB - OBJECTIVE: To examine the expression of unfolded protein response (UPR) genes, a set of genes that are activated to assist in protein trafficking and cellular homeostasis when endoplasmic reticulum (ER) stress occurs, in inflamed and uninflamed periodontal tissues, with or without Russell bodies (RB). RB are a histologically apparent extension of the ER that represents an accumulation of abnormal proteins that cannot be secreted or degraded and may serve as a marker of ER stress. DESIGN: Periodontal tissue specimens were collected and categorised histologically based on the presence of inflammation and the quantity of RB. The differential regulation of 84 UPR-related genes was examined by qRT(2)-PCR. RESULTS: UPR genes related to the inositol-requiring ER-to-nucleus signal kinase (IRE)-1 pathway, molecular chaperones and ER quality control were up-regulated in RB(+) tissues compared with RB(-) tissues, irrespective of inflammation. Inflamed periodontal tissues showed a marked down-regulation of heat shock protein (HSP) 70 family members. CONCLUSION: The presence of RB in inflamed periodontal tissues correlated with the expression of a unique set of ER stress-related genes and therefore may serve as a marker of UPR response in periodontal inflammation. Inflamed periodontal tissues showed a marked down-regulation of UPR genes, in particular HSP70. This may be contributory to disease progression in periodontal disease. PMID- 27179439 TI - Anti-PLA2R Antibodies in Chinese Patients with Membranous Nephropathy. AB - BACKROUND ~This study used two standardized methods to evaluate anti-PLA2R antibody in serum of primary membranous nephropathy (PMN) among Chinese patients to determine Anti-PLA2R antibody distribution and whether immunological reactivity reflected by antibody titer correlates with kidney function parameters. MATERIAL AND METHOD ~Overall, 82 subjects with biopsy-proven primary membranous nephropathy (PMN) , 22 cases with secondary membranous nephropathy (SMN), 40 non-MN patients with established glomerulonephritis, 20 healthy volunteers were recruited from the Division of Nephrology, Nanfang Hospital, China. Anti-PLA2R antibody in the serum of each patient was evaluated by both recombinant cell-based indirect immunofluorescence assay (RC-IFA) and enzyme linked immunosorbent assay (ELISA). Kidney function was assessed by proteinuria for 24 hours, serum albumin, blood urea nitrogen (BUN), serum creatine, serum cystatin C. We assessed the correlation between anti-PLA2R antibody levels and clinical parameter in the PMN patients. RESULTS ~ Fifty-three patients with PMN (64.6%) were positive for anti-PLA2R antibody. The level of antibody determined by RC-IFA ranged from 1:10 to 1:1000 and 0 to 1423 RU/ml by ELISA. The two anti PLA2R test systems correlated very well with each other and reached an agreement of 95.7% for PMN patients. The level of antibody detected by ELISA in patients with PMN also significantly correlated with proteinuria and nephritic-range proteinuria (> 3.5g/day) . CONCLUSIONS ~Anti-PLA2R antibody is sensitive and extremely specific for diagnosis of Chinese patients with primary membranous nephropathy. Concentration of autoantibody against PLA2R is an ideal marker for monitoring the activity of immunological disease. PMID- 27179440 TI - Comparison of suture materials for subcuticular skin closure at cesarean delivery. AB - BACKGROUND: Subcuticular skin closure with suture after cesarean has been shown to result in lower rates of wound complications than with staple closure. However, the optimal choice of suture material for subcuticular skin closure is unclear. Vicryl (a braided multifilament synthetic suture; Ethicon, Somerville, NJ) and Monocryl (a monofilament synthetic suture; Ethicon) are the commonly used suture materials for subcuticular closure of transverse skin incisions after cesarean in the United States. Whereas in vitro and animal studies suggest multifilament suture materials may be associated with a higher risk of wound infection than monofilament sutures, clinical data on their relative effectiveness are limited. OBJECTIVE: We sought to test the hypothesis that Vicryl is associated with a higher rate of wound complications than Monocryl. STUDY DESIGN: This is a secondary analysis of data from a randomized trial in which pregnant women undergoing scheduled or unscheduled cesareans were randomly assigned to preoperative skin preparation with either chlorhexidine-alcohol or iodine-alcohol. Women with low transverse skin incisions who were closed with either 4-0 Monocryl or 4-0 Vicryl were included in this analysis. Choice of suture material was at the discretion of the operating physician. The primary outcome was superficial or deep surgical site infection within 30 days after cesarean. Secondary outcomes were other wound complications. Outcomes were compared between the 2 groups using univariable and multivariable statistics. RESULTS: Of 1082 patients who had follow-up after discharge in the primary trial, 871 had subcuticular suture: 180 with 4-0 Vicryl and 691 with 4-0 Monocryl. Skin closure with Vicryl or Monocryl did not significantly differ between women allocated to chlorhexidine-alcohol or iodine-alcohol (51.1% vs 49.4%, P = .67). There was no significant difference in the risk of surgical site infection in women closed with Vicryl compared with Monocryl (11 [6.1%] vs 35 [5.1%]; P = .58; adjusted odds ratio, 1.23; 95% confidence interval, 0.60-2.49). Rates of other wound complications were also not significantly different. Risks of surgical site infection were similar with Vicryl and Monocryl closure in all subgroups assessed. The relative risks were not materially affected by whether diabetes or obesity was present, cesarean was scheduled or unscheduled, primary or repeat cesarean, or the subcutaneous layer was closed. Post hoc power analysis indicated that we had 80% power to detect >2-fold difference in surgical site infections. CONCLUSION: Subcuticular skin closure with 4-0 Vicryl is associated with comparable rates of surgical site infection and other wound complications as 4-0 Monocryl. While this is an observational study with the potential for selection bias and residual confounding, our results suggest physician preference is acceptable for choice of subcuticular suture material at cesarean. PMID- 27179441 TI - Site of delivery contribution to black-white severe maternal morbidity disparity. AB - BACKGROUND: The black-white maternal mortality disparity is the largest disparity among all conventional population perinatal health measures, and the mortality gap between black and white women in New York City has nearly doubled in recent years. For every maternal death, 100 women experience severe maternal morbidity, a life-threatening diagnosis, or undergo a life-saving procedure during their delivery hospitalization. Like maternal mortality, severe maternal morbidity is more common among black than white women. A significant portion of maternal morbidity and mortality is preventable, making quality of care in hospitals a critical lever for improving outcomes. Hospital variation in risk-adjusted severe maternal morbidity rates exists. The extent to which variation in hospital performance on severe maternal morbidity rates contributes to black-white disparities in New York City hospitals has not been studied. OBJECTIVE: We examined the extent to which black-white differences in severe maternal morbidity rates in New York City hospitals can be explained by differences in the hospitals in which black and white women deliver. STUDY DESIGN: We conducted a population based study using linked 2011-2013 New York City discharge and birth certificate datasets (n = 353,773 deliveries) to examine black-white differences in severe maternal morbidity rates in New York City hospitals. A mixed-effects logistic regression with a random hospital-specific intercept was used to generate risk standardized severe maternal morbidity rates for each hospital (n = 40). We then assessed differences in the distributions of black and white deliveries among these hospitals. RESULTS: Severe maternal morbidity occurred in 8882 deliveries (2.5%) and was higher among black than white women (4.2% vs 1.5%, P < .001). After adjustment for patient characteristics and comorbidities, the risk remained elevated for black women (odds ratio, 2.02; 95% confidence interval, 1.89-2.17). Risk-standardized severe maternal morbidity rates among New York City hospitals ranged from 0.8 to 5.7 per 100 deliveries. White deliveries were more likely to be delivered in low-morbidity hospitals: 65% of white vs 23% of black deliveries occurred in hospitals in the lowest tertile for morbidity. We estimated that black-white differences in delivery location may contribute as much as 47.7% of the racial disparity in severe maternal morbidity rates in New York City. CONCLUSION: Black mothers are more likely to deliver at higher risk-standardized severe maternal morbidity hospitals than are white mothers, contributing to black white disparities. More research is needed to understand the attributes of high performing hospitals and to share best practices among hospitals. PMID- 27179443 TI - Maternal voluntary efforts and subsequent gynecologic outcomes. PMID- 27179442 TI - Maternal and pregnancy characteristics affect plasma fibrin monomer complexes and D-dimer reference ranges for venous thromboembolism in pregnancy. AB - BACKGROUND: D-dimers have a high negative predictive value for excluding venous thromboembolism outside of pregnancy but the use in pregnancy remains controversial. A higher cut-off value has been proposed in pregnancy due to a continuous increase across gestation. Fibrin monomer complexes have been considered as an alternative diagnostic tool for exclusion of venous thromboembolism in pregnancy due to their different behavior. OBJECTIVE: We sought to establish normal values of fibrin monomer complexes and D-dimer as a diagnostic tool for the exclusion of venous thromboembolism in pregnancy and examine the effect of maternal and obstetric factors on these markers. STUDY DESIGN: Plasma D-dimer and fibrin monomer complexes were measured by quantitative immunoturbidimetry in 2870 women with singleton pregnancies attending their routine first-trimester hospital visit in a prospective screening study for adverse obstetric outcome. Multiple regression analysis was used to determine maternal characteristics and obstetric factors affecting the plasma concentrations and converting these into multiple of the median values after adjusting for significant maternal and obstetric characteristics. RESULTS: Plasma fibrin monomer complexes increased with maternal weight and were lower in women with a history of cocaine abuse and chronic hypertension. D-dimers increased with gestational age and maternal weight and were higher in sickle cell carriers and in women of African and South Asian racial origin compared to Caucasians. CONCLUSION: Fibrin monomer complexes and D-dimers are affected by maternal and obstetric characteristics rather than only gestational age. The utility of these fibrin-linked markers as a tool for exclusion of venous thromboembolism in pregnancy might be improved by adjusting for patient-specific characteristics. PMID- 27179444 TI - The Polycomb group protein CLF emerges as a specific tri-methylase of H3K27 regulating gene expression and development in Physcomitrella patens. AB - Packaging of eukaryotic DNA largely depends on histone modifications that affect the accessibility of DNA to transcriptional regulators, thus controlling gene expression. The Polycomb group (PcG) chromatin remodeling complex deposits a methyl group on lysine 27 of histone 3 leading to repressed gene expression. Plants encode homologs of the Enhancer of zeste (E(z)), a component of the PcG complex from Drosophila, one of which is a SET domain protein designated CURLY LEAF (CLF). Although this SET domain protein exhibits a strong correlation with the presence of the H3K27me3 mark in plants, the methyl-transferase activity and specificity of its SET domain have not been directly tested in-vivo. Using the evolutionary early-diverged land plant model species Physcomitrella patens we show that abolishment of a single copy gene PpCLF, as well as an additional member of the PcG complex, FERTILIZATION-INDEPENDENT ENDOSPERM (PpFIE), results in a specific loss of tri-methylation of H3K27. Using site-directed mutagenesis of key residues, we revealed that H3K27 tri-methylation is mediated by the SET domain of the CLF protein. Moreover, the abolishment of H3K27me3 led to enhanced expression of transcription factor genes. This in turn led to the development of fertilization-independent sporophyte-like structures, as observed in PpCLF and PpFIE null mutants. Overall, our results demonstrate the role of PpCLF as a SET protein in tri-methylation of H3K27 in-vivo and the importance of this modification in regulating the expression of transcription factor genes involved in developmental programs of P. patens. PMID- 27179445 TI - Expression of microRNA-195 is transactivated by Sp1 but inhibited by histone deacetylase 3 in hepatocellular carcinoma cells. AB - MiR-195 expression is frequently reduced in various cancers, but its underlying mechanisms remain unknown. To explore whether abnormal transcription contributed to miR-195 downregulation in hepatocellular carcinoma (HCC), we characterized the -2165-bp site upstream of mature miR-195 as transcription start site and the -2.4 to -2.0-kb fragment as the promoter of miR-195 gene. Subsequent investigation showed that deletion of the predicted Sp1 binding site decreased the miR-195 promoter activity; Sp1 silencing significantly reduced the miR-195 promoter activity and the endogenous miR-195 level; Sp1 directly interacted with the miR 195 promoter in vitro and in vivo. These data suggest Sp1 as a transactivator for miR-195 transcription. Interestingly, miR-195 expression was also subjected to epigenetic regulation. Histone deacetylase 3 (HDAC3) could anchor to the miR-195 promoter via interacting with Sp1 and consequently repress the Sp1-mediated miR 195 transactivation by deacetylating histone in HCC cells. Consistently, substantial increase of HDAC3 protein was detected in human HCC tissues and HDAC3 upregulation was significantly correlated with miR-195 downregulation, suggesting that HDAC3 elevation may represent an important cause for miR-195 reduction in HCC. Our findings uncover the mechanisms underlying the transcriptional regulation and expression deregulation of miR-195 in HCC cells and provide new insight into microRNA biogenesis in cancer cells. PMID- 27179446 TI - Functional morphology of the maxillary and propharyngeal glands of Monomorium pharaonis (L.). AB - The maxillary and propharyngeal gland of all 3 castes of Monomorium pharaonis were examined with light and electron microscopy. Although both glands possess a pouch in which secretion can be stored temporarily, a proper reservoir is lacking. The paired maxillary gland opens at the base of the maxilla and consists of 4 secretory cells, which are smaller in workers as compared to queens and males. A digestive role is unlikely as the gland is not directly linked to the digestive system and the amount of rER is negligible. The propharyngeal gland consists of 2 clusters of 16 secretory cells, which open in the pharyngeal atrium through a duct. Secretory cells are smallest in males. Two types of endoplasmic vesicles are observed around the end apparatus, suggesting a release of at least 2 substances. High levels of rER indicate the production of digestive enzymes as one of its functions. No differences between mated versus virgin queens were observed for both glands. Further experiments on chemical and behavioural essays can improve our understanding of the role of both glands in the ant colony. Literature on this topic is very inconsistent. We provide a survey to unravel this chaotic nomenclature issue. PMID- 27179447 TI - A framework for the automatic detection and characterization of brain malformations: Validation on the corpus callosum. AB - In this paper, we extend the one-class Support Vector Machine (SVM) and the regularized discriminative direction analysis to the Multiple Kernel (MK) framework, providing an effective analysis pipeline for the detection and characterization of brain malformations, in particular those affecting the corpus callosum. The detection of the brain malformations is currently performed by visual inspection of MRI images, making the diagnostic process sensible to the operator experience and subjectiveness. The method we propose addresses these problems by automatically reproducing the neuroradiologist's approach. One-class SVMs are appropriate to cope with heterogeneous brain abnormalities that are considered outliers. The MK framework allows to efficiently combine the different geometric features that can be used to describe brain structures. Moreover, the regularized discriminative direction analysis is exploited to highlight the specific malformative patterns for each patient. We performed two different experiments. Firstly, we tested the proposed method to detect the malformations of the corpus callosum on a 104 subject dataset. Results showed that the proposed pipeline can classify the subjects with an accuracy larger than 90% and that the discriminative direction analysis can highlight a wide range of malformative patterns (e.g., local, diffuse, and complex abnormalities). Secondly, we compared the diagnosis of four neuroradiologists on a dataset of 128 subjects. The diagnosis was performed both in blind condition and using the classifier and the discriminative direction outputs. Results showed that the use of the proposed pipeline as an assisted diagnosis tool improves the inter-subject variability of the diagnosis. Finally, a graphical representation of the discriminative direction analysis was proposed to enhance the interpretability of the results and provide the neuroradiologist with a tool to fully and clearly characterize the patient malformations at single-subject level. PMID- 27179448 TI - Economic and environmental sustainability of an AnMBR treating urban wastewater and organic fraction of municipal solid waste. AB - The objective of this study was to evaluate the economic and environmental sustainability of a submerged anaerobic membrane bioreactor (AnMBR) treating urban wastewater (UWW) and organic fraction of municipal solid waste (OFMSW) at ambient temperature in mild/hot climates. To this aim, power requirements, energy recovery from methane (biogas methane and methane dissolved in the effluent), consumption of reagents for membrane cleaning, and sludge handling (polyelectrolyte and energy consumption) and disposal (farmland, landfilling and incineration) were evaluated within different operating scenarios. Results showed that, for the operating conditions considered in this study, AnMBR technology is likely to be a net energy producer, resulting in considerable cost savings (up to ?0.023 per m(3) of treated water) when treating low-sulphate influent. Life cycle analysis (LCA) results revealed that operating at high sludge retention times (70 days) and treating UWW jointly with OFMSW enhances the overall environmental performance of AnMBR technology. PMID- 27179449 TI - New trans dichloro (triphenylphosphine)platinum(II) complexes containing N (butyl),N-(arylmethyl)amino ligands: Synthesis, cytotoxicity and mechanism of action. AB - Some new platinum(II) complexes have been prepared, of general formula trans [PtCl2(PPh3){NH(Bu)CH2Ar}], where the dimension of the Ar residue in the secondary amines has been varied from small phenyl to large pyrenyl group. The obtained complexes, tested in vitro towards a panel of human tumor cell lines showed an interesting antiproliferative effect on both cisplatin-sensitive and resistant cells. For the most cytotoxic derivative 2a the investigation on the mechanism of action highlighted the ability to induce apoptosis on resistant cells and interestingly, to inhibit the catalytic activity of topoisomerase II. PMID- 27179450 TI - Tauroursodeoxycholate improves 2,4,6-trinitrobenzenesulfonic acid-induced experimental acute ulcerative colitis in mice. AB - Ulcerative colitis is a chronic nonspecific inflammatory disease of unknown cause. The aim of this study was to evaluate the anti-inflammatory effect of tauroursodeoxycholate in 2, 4, 6-trinitrobenzenesulfonic acid-induced experimental colitis in mice. After the induction of colitis for 24h, the mice were administrated orally with tauroursodeoxycholate (20, 40 and 60mg/kg) and sulfasalazine (500mg/kg) by gavage for 7 consecutive days. The inhibition effects were evaluated by the body of weight change, survival rate, macroscopical and histological evaluations. Besides, myeloperoxidase (MPO) activity, interleukin (IL)-1beta, interferon (IFN)-gamma and tumour necrosis factor-alpha (TNF-alpha) in colon tissue were also determined by enzyme-linked immunosorbent assay. Treatment with different doses of tauroursodeoxycholate (20, 40 and 60mg/kg) significantly improved the body weight change, decreased the macroscopic and histopathological scores. Compared with the model group, the accumulation of MPO activity, the colonic tissue levels of IL-1beta, IFN-gamma and TNF-alpha were significantly reduced in the tauroursodeoxycholate treated groups. Moreover, tauroursodeoxycholate assuaged the symptoms of colitis. These results suggested that tauroursodeoxycholate has an anti-inflammatory effect in TNBS-induced ulcerative colitis in mice. PMID- 27179451 TI - Converging advances in science, policy and public awareness: A time of great opportunity and change in addiction treatment. AB - Scientific advances, increased public awareness about addiction as a disease, and significant changes in public policy have led to transformational changes in this field. Preclinical and clinical studies highlighted in this issue have supported the emerging concept of substance use disorders as a novel major concern within the healthcare community. In this Commentary, we discuss the potential impact of recent legislation (Affordable Care Act and the Mental Health Parity and Addiction Equity Act) when fully implemented to end the real and perceived segregation of addiction and substance abuse disorders from mainstream healthcare and insurance reimbursement. These legislative changes, along with the diligence of public interest and scientific advances, have the potential to move prevention and treatment of substance use disorders to mainstream healthcare, and to educate professionals appropriately on the prevention and treatment of substance abuse. PMID- 27179452 TI - In the search for integrative biomarker of resilience to psychological stress. AB - Psychological resilience can be defined as individual's ability to withstand and adapt to adverse and traumatic events. Resilience is traditionally assessed by subjective reports, a method that is susceptible to self-report bias. An ideal solution to this challenge is the introduction of standardised and validated physiological and/or biological predictors of resilience. We provide a summary of the major concepts in the field of resilience followed by a detailed critical review of the literature around physiological, neurochemical and immune markers of resilience. We conclude that in future experimental protocols, biological markers of resilience should be assesses both during baseline and during laboratory stressors. In the former case the most promising candidates are represented by heart rate variability and by in vitro immune cells assay; in the latter case-by startle responses (especially their habituation) during stress challenge and by cardiovascular recovery after stress, and by cortisol, DHEA and cytokine responses. Importantly, they should be used in combination to enhance predictive power. PMID- 27179453 TI - Metabolic reprogramming by the pyruvate dehydrogenase kinase-lactic acid axis: Linking metabolism and diverse neuropathophysiologies. AB - Emerging evidence indicates that there is a complex interplay between metabolism and chronic disorders in the nervous system. In particular, the pyruvate dehydrogenase (PDH) kinase (PDK)-lactic acid axis is a critical link that connects metabolic reprogramming and the pathophysiology of neurological disorders. PDKs, via regulation of PDH complex activity, orchestrate the conversion of pyruvate either aerobically to acetyl-CoA, or anaerobically to lactate. The kinases are also involved in neurometabolic dysregulation under pathological conditions. Lactate, an energy substrate for neurons, is also a recently acknowledged signaling molecule involved in neuronal plasticity, neuron glia interactions, neuroimmune communication, and nociception. More recently, the PDK-lactic acid axis has been recognized to modulate neuronal and glial phenotypes and activities, contributing to the pathophysiologies of diverse neurological disorders. This review covers the recent advances that implicate the PDK-lactic acid axis as a novel linker of metabolism and diverse neuropathophysiologies. We finally explore the possibilities of employing the PDK lactic acid axis and its downstream mediators as putative future therapeutic strategies aimed at prevention or treatment of neurological disorders. PMID- 27179454 TI - EXponentially Converging Eradication Pulse Train (EXCEPT) for solvent-signal suppression in investigations with variable T(1) times. AB - Selective presaturation is a common technique for suppressing excessive solvent signals during proton NMR analysis of dilute samples in protic solvents. When the solvent T1 relaxation time constant varies within a series of samples, parameters for the presaturation sequence must often be re-adjusted for each sample. The EXCEPT (EXponentially Converging Eradication Pulse Train) presaturation pulse sequence was developed to eliminate time consuming pulse-parameter re optimization as long as the variation in the solvent's T1 remains within an order of magnitude. EXCEPT consists of frequency-selective inversion pulses with progressively decreasing interpulse delays. The interpulse delays were optimized to encompass T1 relaxation times ranging from 1 to 10s, but they can be easily adjusted by a single factor for other ranges that fall within an order of magnitude with respect to T1. Sequences with different numbers of inversion pulses were tested to maximize suppression while minimizing the number of pulses and thus the total time needed for suppression. The EXCEPT-16 experiment, where 16 denotes the number of inversion pulses, was found satisfactory for many standard applications. Experimental results demonstrate that EXCEPT provides effective T1-insensitive solvent suppression as predicted by the theory. The robustness of EXCEPT with respect to changes in solvent T1 allows NMR investigations to be carried out for a series of samples without the need for pulse-parameter re-optimization for each sample. PMID- 27179455 TI - ARTSY-J: Convenient and precise measurement of (3)JHNHalpha couplings in medium size proteins from TROSY-HSQC spectra. AB - A new and convenient method, named ARTSY-J, is introduced that permits extraction of the (3)JHNHalpha couplings in proteins from the relative intensities in a pair of (15)N-(1)H TROSY-HSQC spectra. The pulse scheme includes (3)JHNHalpha dephasing of the narrower TROSY (1)H(N)-{(15)N} doublet component during a delay, integrated into the regular two-dimensional TROSY-HSQC pulse scheme, and compares the obtained intensity with a reference spectrum where (3)JHNHalpha dephasing is suppressed. The effect of passive (1)H(alpha) spin flips downscales the apparent (3)JHNHalpha coupling by a uniform factor that depends approximately linearly on both the duration of the (3)JHNHalpha dephasing delay and the (1)H-(1)H cross relaxation rate. Using such a correction factor, which accounts for the effects of both inhomogeneity of the radiofrequency field and (1)H(alpha) spin flips, agreement between prior and newly measured values for the small model protein GB3 is better than 0.3Hz. Measurement for the HIV-1 protease homodimer (22kDa) yields (3)JHNHalpha values that agree to better than 0.7Hz with predictions made on the basis of a previously parameterized Karplus equation. Although for Gly residues the two individual (3)JHNHalpha couplings cannot be extracted from a single set of ARTSY-J spectra, the measurement provides valuable phi angle information. PMID- 27179456 TI - New high homogeneity 55T pulsed magnet for high field NMR. AB - Pulsed magnets can produce magnetic fields largely exceeding those achieved with resistive or even hybrid magnets. This kind of magnet is indispensable in studies of field-induced phenomena which occur only in high magnetic field. A new high homogeneous pulsed magnet capable of producing field up to 55T and specially designed for NMR experiments was built and tested. Experimentally observed homogeneity of magnetic field in central part of the magnet is 10ppm over a sample volume of 2-3mm(3) at 12T and 30ppm at 47T, which are the best values ever reported for a pulsed magnet. Reasons which affect the field profile and reduce homogeneity at high field are discussed. PMID- 27179457 TI - INDISIM-Paracoccus, an individual-based and thermodynamic model for a denitrifying bacterium. AB - We have developed an individual-based model for denitrifying bacteria. The model, called INDISIM-Paracoccus, embeds a thermodynamic model for bacterial yield prediction inside the individual-based model INDISIM, and is designed to simulate the bacterial cell population behavior and the product dynamics within the culture. The INDISIM-Paracoccus model assumes a culture medium containing succinate as a carbon source, ammonium as a nitrogen source and various electron acceptors such as oxygen, nitrate, nitrite, nitric oxide and nitrous oxide to simulate in continuous or batch culture the different nutrient-dependent cell growth kinetics of the bacterium Paracoccus denitrificans. The individuals in the model represent microbes and the individual-based model INDISIM gives the behavior-rules that they use for their nutrient uptake and reproduction cycle. Three previously described metabolic pathways for P. denitrificans were selected and translated into balanced chemical equations using a thermodynamic model. These stoichiometric reactions are an intracellular model for the individual behavior-rules for metabolic maintenance and biomass synthesis and result in the release of different nitrogen oxides to the medium. The model was implemented using the NetLogo platform and it provides an interactive tool to investigate the different steps of denitrification carried out by a denitrifying bacterium. The simulator can be obtained from the authors on request. PMID- 27179458 TI - A model of space-fractional-order diffusion in the glial scar. AB - Implantation of neuroprosthetic electrodes induces a stereotypical state of neuroinflammation, which is thought to be detrimental for the neurons surrounding the electrode. Mechanisms of this type of neuroinflammation are still poorly understood. Recent experimental and theoretical results point to a possible role of the diffusing species in this process. The paper considers a model of anomalous diffusion occurring in the glial scar around a chronic implant in two simple geometries - a separable rectilinear electrode and a cylindrical electrode, which are solvable exactly. We describe a hypothetical extended source of diffusing species and study its concentration profile in steady-state conditions. Diffusion transport is assumed to obey a fractional-order Fick law, derivable from physically realistic assumptions using a fractional calculus approach. Presented fractional-order distribution morphs into integer-order diffusion in the case of integral fractional exponents. The model demonstrates that accumulation of diffusing species can occur and the scar properties (i.e. tortuosity, fractional order, scar thickness) and boundary conditions can influence such accumulation. The observed shape of the concentration profile corresponds qualitatively with GFAP profiles reported in the literature. The main difference with respect to the previous studies is the explicit incorporation of the apparatus of fractional calculus without assumption of an ad hoc tortuosity parameter. The approach can be adapted to other studies of diffusion in biological tissues, for example of biomolecules or small drug molecules. PMID- 27179459 TI - Machine learning approaches for discrimination of Extracellular Matrix proteins using hybrid feature space. AB - Extracellular Matrix (ECM) proteins are the vital type of proteins that are secreted by resident cells. ECM proteins perform several significant functions including adhesion, differentiation, cell migration and proliferation. In addition, ECM proteins regulate angiogenesis process, embryonic development, tumor growth and gene expression. Due to tremendous biological significance of the ECM proteins and rapidly increases of protein sequences in databases, it is indispensable to introduce a new high throughput computation model that can accurately identify ECM proteins. Various traditional models have been developed, but they are laborious and tedious. In this work, an effective and high throughput computational classification model is proposed for discrimination of ECM proteins. In this model, protein sequences are formulated using amino acid composition, pseudo amino acid composition (PseAAC) and di-peptide composition (DPC) techniques. Further, various combination of feature extraction techniques are fused to form hybrid feature spaces. Several classifiers were employed. Among these classifiers, K-Nearest Neighbor obtained outstanding performance in combination with the hybrid feature space of PseAAC and DPC. The obtained accuracy of our proposed model is 96.76%, which the highest success rate has been reported in the literature so far. PMID- 27179460 TI - Genetic algorithm based approach to optimize phenotypical traits of virtual rice. AB - How to select and combine good traits of rice to get high-production individuals is one of the key points in developing crop ideotype cultivation technologies. Existing cultivation methods for producing ideal plants, such as field trials and crop modeling, have some limits. In this paper, we propose a method based on a genetic algorithm (GA) and a functional-structural plant model (FSPM) to optimize plant types of virtual rice by dynamically adjusting phenotypical traits. In this algorithm, phenotypical traits such as leaf angles, plant heights, the maximum number of tiller, and the angle of tiller are considered as input parameters of our virtual rice model. We evaluate the photosynthetic output as a function of these parameters, and optimized them using a GA. This method has been implemented on GroIMP using the modeling language XL (eXtended L-System) and RGG (Relational Growth Grammar). A double haploid population of rice is adopted as test material in a case study. Our experimental results show that our method can not only optimize the parameters of rice plant type and increase the amount of light absorption, but can also significantly increase crop yield. PMID- 27179461 TI - Games of multicellularity. AB - Evolutionary game dynamics are often studied in the context of different population structures. Here we propose a new population structure that is inspired by simple multicellular life forms. In our model, cells reproduce but can stay together after reproduction. They reach complexes of a certain size, n, before producing single cells again. The cells within a complex derive payoff from an evolutionary game by interacting with each other. The reproductive rate of cells is proportional to their payoff. We consider all two-strategy games. We study deterministic evolutionary dynamics with mutations, and derive exact conditions for selection to favor one strategy over another. Our main result has the same symmetry as the well-known sigma condition, which has been proven for stochastic game dynamics and weak selection. For a maximum complex size of n=2 our result holds for any intensity of selection. For n>=3 it holds for weak selection. As specific examples we study the prisoner's dilemma and hawk-dove games. Our model advances theoretical work on multicellularity by allowing for frequency-dependent interactions within groups. PMID- 27179462 TI - Association of ICAM-1 K469E polymorphism with dengue infection in North Indian population. AB - Dengue infection is caused by flavivirus is one of the leading cause of mortality. There are certain factors which play role in the transformation of a mild form of the disease (DF) into a severe form (DHF) but the most important ones are: viral strain virulence, host genetics, and host immune status. In severe dengue infection, plasma leakage occurs due to vascular endothelial cell activation through expression of adhesion molecule like intercellular cell adhesion molecule-1 (ICAM-1). A total of 100 dengue patients (DF; n = 53 and DHF/DSS; n = 47) and 200 healthy controls were included in the study. ICAM-1 K469E genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (PCR- RFLP). Expression of ICAM-1 mRNA was done by Real time reverse transcription- PCR (rRT-PCR). Patients with homozygous genotype (EE) have 3.22 fold risk (P = 0.008) of developing severe form of disease (DHF/DSS) as compared to other genotypes. Patients with DHF/DSS exhibit higher expression of ICAM-1 mRNA as compared to dengue fever and controls (P = 0.001 and < 0.001). Patients (DHF/DSS) with homozygous (EE) genotype exhibit higher expression of ICAM-1 mRNA when compared with wild type (KK) genotype (P = 0.005). This study suggests a possible association between the ICAM-1 polymorphism and the disease severity. PMID- 27179463 TI - Unmasking a Role for Noninvasive Ventilation in Early Acute Respiratory Distress Syndrome. PMID- 27179465 TI - Path optimization by a variational reaction coordinate method. II. Improved computational efficiency through internal coordinates and surface interpolation. AB - Reaction path optimization is being used more frequently as an alternative to the standard practice of locating a transition state and following the path downhill. The Variational Reaction Coordinate (VRC) method was proposed as an alternative to chain-of-states methods like nudged elastic band and string method. The VRC method represents the path using a linear expansion of continuous basis functions, allowing the path to be optimized variationally by updating the expansion coefficients to minimize the line integral of the potential energy gradient norm, referred to as the Variational Reaction Energy (VRE) of the path. When constraints are used to control the spacing of basis functions and to couple the minimization of the VRE with the optimization of one or more individual points along the path (representing transition states and intermediates), an approximate path as well as the converged geometries of transition states and intermediates along the path are determined in only a few iterations. This algorithmic efficiency comes at a high per-iteration cost due to numerical integration of the VRE derivatives. In the present work, methods for incorporating redundant internal coordinates and potential energy surface interpolation into the VRC method are described. With these methods, the per iteration cost, in terms of the number of potential energy surface evaluations, of the VRC method is reduced while the high algorithmic efficiency is maintained. PMID- 27179466 TI - Multi-state extrapolation of UV/Vis absorption spectra with QM/QM hybrid methods. AB - In this work, we present a simple approach to simulate absorption spectra from hybrid QM/QM calculations. The goal is to obtain reliable spectra for compounds that are too large to be treated efficiently at a high level of theory. The present approach is based on the extrapolation of the entire absorption spectrum obtained by individual subcalculations. Our program locates the main spectral features in each subcalculation, e.g., band peaks and shoulders, and fits them to Gaussian functions. Each Gaussian is then extrapolated with a formula similar to that of ONIOM (Our own N-layered Integrated molecular Orbital molecular Mechanics). However, information about individual excitations is not necessary so that difficult state-matching across subcalculations is avoided. This multi-state extrapolation thus requires relatively low implementation effort while affording maximum flexibility in the choice of methods to be combined in the hybrid approach. The test calculations show the efficacy and robustness of this methodology in reproducing the spectrum computed for the entire molecule at a high level of theory. PMID- 27179467 TI - Tight-binding approximations to time-dependent density functional theory - A fast approach for the calculation of electronically excited states. AB - We propose a new method of calculating electronically excited states that combines a density functional theory based ground state calculation with a linear response treatment that employs approximations used in the time-dependent density functional based tight binding (TD-DFTB) approach. The new method termed time dependent density functional theory TD-DFT+TB does not rely on the DFTB parametrization and is therefore applicable to systems involving all combinations of elements. We show that the new method yields UV/Vis absorption spectra that are in excellent agreement with computationally much more expensive TD-DFT calculations. Errors in vertical excitation energies are reduced by a factor of two compared to TD-DFTB. PMID- 27179468 TI - Approximate but accurate quantum dynamics from the Mori formalism: I. Nonequilibrium dynamics. AB - We present a formalism that explicitly unifies the commonly used Nakajima-Zwanzig approach for reduced density matrix dynamics with the more versatile Mori theory in the context of nonequilibrium dynamics. Employing a Dyson-type expansion to circumvent the difficulty of projected dynamics, we obtain a self-consistent equation for the memory kernel which requires only knowledge of normally evolved auxiliary kernels. To illustrate the properties of the current approach, we focus on the spin-boson model and limit our attention to the use of a simple and inexpensive quasi-classical dynamics, given by the Ehrenfest method, for the calculation of the auxiliary kernels. For the first time, we provide a detailed analysis of the dependence of the properties of the memory kernels obtained via different projection operators, namely, the thermal (Redfield-type) and population based (NIBA-type) projection operators. We further elucidate the conditions that lead to short-lived memory kernels and the regions of parameter space to which this program is best suited. Via a thorough analysis of the different closures available for the auxiliary kernels and the convergence properties of the self-consistently extracted memory kernel, we identify the mechanisms whereby the current approach leads to a significant improvement over the direct usage of standard semi- and quasi-classical dynamics. PMID- 27179464 TI - Perspective: Defining and quantifying the role of dynamics in enzyme catalysis. AB - Enzymes control chemical reactions that are key to life processes, and allow them to take place on the time scale needed for synchronization between the relevant reaction cycles. In addition to general interest in their biological roles, these proteins present a fundamental scientific puzzle, since the origin of their tremendous catalytic power is still unclear. While many different hypotheses have been put forward to rationalize this, one of the proposals that has become particularly popular in recent years is the idea that dynamical effects contribute to catalysis. Here, we present a critical review of the dynamical idea, considering all reasonable definitions of what does and does not qualify as a dynamical effect. We demonstrate that no dynamical effect (according to these definitions) has ever been experimentally shown to contribute to catalysis. Furthermore, the existence of non-negligible dynamical contributions to catalysis is not supported by consistent theoretical studies. Our review is aimed, in part, at readers with a background in chemical physics and biophysics, and illustrates that despite a substantial body of experimental effort, there has not yet been any study that consistently established a connection between an enzyme's conformational dynamics and a significant increase in the catalytic contribution of the chemical step. We also make the point that the dynamical proposal is not a semantic issue but a well-defined scientific hypothesis with well-defined conclusions. PMID- 27179469 TI - Generalized quantum master equations in and out of equilibrium: When can one win? AB - Generalized quantum master equations (GQMEs) are an important tool in modeling chemical and physical processes. For a large number of problems, it has been shown that exact and approximate quantum dynamics methods can be made dramatically more efficient, and in the latter case more accurate, by proceeding via the GQME formalism. However, there are many situations where utilizing the GQME approach with an approximate method has been observed to return the same dynamics as using that method directly. Here, for systems both in and out of equilibrium, we provide a more detailed understanding of the conditions under which using an approximate method can yield benefits when combined with the GQME formalism. In particular, we demonstrate the necessary manipulations, which are satisfied by exact quantum dynamics, that are required to recast the memory kernel in a form that can be analytically shown to yield the same result as a direct application of the dynamics regardless of the approximation used. By considering the connections between these forms of the kernel, we derive the conditions that approximate methods must satisfy if they are to offer different results when used in conjunction with the GQME formalism. These analytical results thus provide new insights as to when proceeding via the GQME approach can be used to improve the accuracy of simulations. PMID- 27179470 TI - Matrix elements of explicitly correlated Gaussian basis functions with arbitrary angular momentum. AB - A new algorithm for calculating the Hamiltonian matrix elements with all-electron explicitly correlated Gaussian functions for quantum-mechanical calculations of atoms with arbitrary angular momentum is presented. The calculations are checked on several excited states of three and four electron systems. The presented formalism can be used as unified framework for high accuracy calculations of properties of small atoms and molecules. PMID- 27179471 TI - Molecular dynamics at constant Cauchy stress. AB - The Parrinello-Rahman algorithm for imposing a general state of stress in periodic molecular dynamics simulations is widely used in the literature and has been implemented in many readily available molecular dynamics codes. However, what is often overlooked is that this algorithm controls the second Piola Kirchhoff stress as opposed to the true (Cauchy) stress. This can lead to misinterpretation of simulation results because (1) the true stress that is imposed during the simulation depends on the deformation of the periodic cell, (2) the true stress is potentially very different from the imposed second Piola Kirchhoff stress, and (3) the true stress can vary significantly during the simulation even if the imposed second Piola-Kirchhoff is constant. We propose a simple modification to the algorithm that allows the true Cauchy stress to be controlled directly. We then demonstrate the efficacy of the new algorithm with the example of martensitic phase transformations under applied stress. PMID- 27179472 TI - Resolution-of-identity stochastic time-dependent configuration interaction for dissipative electron dynamics in strong fields. AB - In this contribution, we introduce a method for simulating dissipative, ultrafast many-electron dynamics in intense laser fields. The method is based on the norm conserving stochastic unraveling of the dissipative Liouville-von Neumann equation in its Lindblad form. The N-electron wave functions sampling the density matrix are represented in the basis of singly excited configuration state functions. The interaction with an external laser field is treated variationally and the response of the electronic density is included to all orders in this basis. The coupling to an external environment is included via relaxation operators inducing transition between the configuration state functions. Single electron ionization is represented by irreversible transition operators from the ionizing states to an auxiliary continuum state. The method finds its efficiency in the representation of the operators in the interaction picture, where the resolution-of-identity is used to reduce the size of the Hamiltonian eigenstate basis. The zeroth-order eigenstates can be obtained either at the configuration interaction singles level or from a time-dependent density functional theory reference calculation. The latter offers an alternative to explicitly time dependent density functional theory which has the advantage of remaining strictly valid for strong field excitations while improving the description of the correlation as compared to configuration interaction singles. The method is tested on a well-characterized toy system, the excitation of the low-lying charge transfer state in LiCN. PMID- 27179473 TI - Wave function continuity and the diagonal Born-Oppenheimer correction at conical intersections. AB - We demonstrate that though exact in principle, the expansion of the total molecular wave function as a sum over adiabatic Born-Oppenheimer (BO) vibronic states makes inclusion of the second-derivative nonadiabatic energy term near conical intersections practically problematic. In order to construct a well behaved molecular wave function that has density at a conical intersection, the individual BO vibronic states in the summation must be discontinuous. When the second-derivative nonadiabatic terms are added to the Hamiltonian, singularities in the diagonal BO corrections (DBOCs) of the individual BO states arise from these discontinuities. In contrast to the well-known singularities in the first derivative couplings at conical intersections, these singularities are non integrable, resulting in undefined DBOC matrix elements. Though these singularities suggest that the exact molecular wave function may not have density at the conical intersection point, there is no physical basis for this constraint. Instead, the singularities are artifacts of the chosen basis of discontinuous functions. We also demonstrate that continuity of the total molecular wave function does not require continuity of the individual adiabatic nuclear wave functions. We classify nonadiabatic molecular dynamics methods according to the constraints placed on wave function continuity and analyze their formal properties. Based on our analysis, it is recommended that the DBOC be neglected when employing mixed quantum-classical methods and certain approximate quantum dynamical methods in the adiabatic representation. PMID- 27179475 TI - Mirrored continuum and molecular scale simulations of the ignition of high pressure phases of RDX. AB - We present a mirrored atomistic and continuum framework that is used to describe the ignition of energetic materials, and a high-pressure phase of RDX in particular. The continuum formulation uses meaningful averages of thermodynamic properties obtained from the atomistic simulation and a simplification of enormously complex reaction kinetics. In particular, components are identified based on molecular weight bin averages and our methodology assumes that both the averaged atomistic and continuum simulations are represented on the same time and length scales. The atomistic simulations of thermally initiated ignition of RDX are performed using reactive molecular dynamics (RMD). The continuum model is based on multi-component thermodynamics and uses a kinetics scheme that describes observed chemical changes of the averaged atomistic simulations. Thus the mirrored continuum simulations mimic the rapid change in pressure, temperature, and average molecular weight of species in the reactive mixture. This mirroring enables a new technique to simplify the chemistry obtained from reactive MD simulations while retaining the observed features and spatial and temporal scales from both the RMD and continuum model. The primary benefit of this approach is a potentially powerful, but familiar way to interpret the atomistic simulations and understand the chemical events and reaction rates. The approach is quite general and thus can provide a way to model chemistry based on atomistic simulations and extend the reach of those simulations. PMID- 27179476 TI - Quantitative velocity modulation spectroscopy. AB - Velocity Modulation Spectroscopy (VMS) is arguably the most important development in the 20th century for spectroscopic study of molecular ions. For decades, interpretation of VMS lineshapes has presented challenges due to the intrinsic covariance of fit parameters including velocity modulation amplitude, linewidth, and intensity. This limitation has stifled the growth of this technique into the quantitative realm. In this work, we show that subtle changes in the lineshape can be used to help address this complexity. This allows for determination of the linewidth, intensity relative to other transitions, velocity modulation amplitude, and electric field strength in the positive column of a glow discharge. Additionally, we explain the large homogeneous component of the linewidth that has been previously described. Using this component, the ion mobility can be determined. PMID- 27179474 TI - Molecular dynamics of protein A and a WW domain with a united-residue model including hydrodynamic interaction. AB - The folding of the N-terminal part of the B-domain of staphylococcal protein A (PDB ID: 1BDD, a 46-residue three-alpha-helix bundle) and the formin-binding protein 28 WW domain (PDB ID: 1E0L, a 37-residue three-stranded anti-parallel beta protein) was studied by means of Langevin dynamics with the coarse-grained UNRES force field to assess the influence of hydrodynamic interactions on protein folding pathways and kinetics. The unfolded, intermediate, and native-like structures were identified by cluster analysis, and multi-exponential functions were fitted to the time dependence of the fractions of native and intermediate structures, respectively, to determine bulk kinetics. It was found that introducing hydrodynamic interactions slows down both the formation of an intermediate state and the transition from the collapsed structures to the final native-like structures by creating multiple kinetic traps. Therefore, introducing hydrodynamic interactions considerably slows the folding, as opposed to the results obtained from earlier studies with the use of Go-like models. PMID- 27179477 TI - Phase-resolved two-dimensional terahertz spectroscopy including off-resonant interactions beyond the chi((3)) limit. AB - We present the first two-dimensional (2D) terahertz (THz) experiment with three phase-locked THz pulses and a fully phase-resolved detection of the nonlinearly emitted field by electrooptic sampling. In a prototype experiment we study the ultrafast dynamics of nonlinear two-phonon and two-photon interband coherences in the narrow-gap semiconductor InSb. Due to the extraordinarily large optical interband dipole of InSb the experiments were performed in the strongly nonperturbative regime of light-matter interaction allowing for impulsive off resonant excitation of both two-phonon coherences and two-photon interband coherences, the ultrafast dynamics of which is experimentally observed as a function of the waiting time in the three-pulse 2D experiment. Our novel three pulse 2D THz spectroscopy paves the way for the detailed investigation of nonlinear quantum coherences in solids and holds potential for an extension to other systems. PMID- 27179478 TI - State-resolved differential and integral cross sections for the Ne + H2 (+) (v = 0-2, j = 0) -> NeH(+) + H reaction. AB - State-to-state quantum dynamic calculations for the proton transfer reaction Ne + H2 (+) (v = 0-2, j = 0) are performed on the most accurate LZHH potential energy surface, with the product Jacobi coordinate based time-dependent wave packet method including the Coriolis coupling. The J = 0 reaction probabilities for the title reaction agree well with previous results in a wide range of collision energy of 0.2-1.2 eV. Total integral cross sections are in reasonable agreement with the available experiment data. Vibrational excitation of the reactant is much more efficient in enhancing the reaction cross sections than translational and rotational excitation. Total differential cross sections are found to be forward-backward peaked with strong oscillations, which is the indication of the complex-forming mechanism. As the collision energy increases, state-resolved differential cross section changes from forward-backward symmetric peaked to forward scattering biased. This forward bias can be attributed to the larger J partial waves, which makes the reaction like an abstraction process. Differential cross sections summed over two different sets of J partial waves for the v = 0 reaction at the collision energy of 1.2 eV are plotted to illustrate the importance of large J partial waves in the forward bias of the differential cross sections. PMID- 27179479 TI - Extensive theoretical study on electronically excited states of calcium monochloride: Molecular laser cooling and production of ultracold chlorine atoms. AB - Nine doublet Lambda-S states of calcium monochloride (CaCl) are calculated using the internally contracted multireference configuration interaction method with the Davidson correction. Both the core subvalence and spin-orbit coupling effects are taken into account. Laser cooling of CaCl and production of ultracold chlorine atoms are investigated and assessed. Our computed spectroscopic constants and radiative lifetimes match the available experimental data very well. The determined Franck-Condon factors and vibrational branching ratios of the A(2)Pi1/2(nu('))<-X(2)Sigma1/2 (+)(nu) transition are highly diagonally distributed and the evaluated radiative lifetime for the A(2)Pi1/2(nu' = 0) state is 28.2 ns, which is short enough for rapid laser cooling. Subsequently, detection of cold molecules via resonance enhanced multiphoton ionization to determine the final quantum state populations is discussed and the ionization energy calculated. A multi-pulse excitation scheme is proposed for producing ultracold chlorine atoms from zero-energy photodissociation of the cooled CaCl. Our results demonstrate the possibility of producing ultracold CaCl molecules and Cl atoms. PMID- 27179480 TI - Simulation of the single-vibronic-level emission spectra of HAsO and DAsO. AB - The single-vibronic-level (SVL) emission spectra of HAsO and DAsO have been simulated by electronic structure/Franck-Condon factor calculations to confirm the spectral molecular carrier and to investigate the electronic states involved. Various multi-reference (MR) methods, namely, NEVPT2 (n-electron valence state second order perturbation theory), RSPT2-F12 (explicitly correlated Rayleigh Schrodinger second order perturbation theory), and MRCI-F12 (explicitly correlated multi-reference configuration interaction) were employed to compute the geometries and relative electronic energies for the X(1)A(') and A(1)A(") states of HAsO. These are the highest level calculations on these states yet reported. The MRCI-F12 method gives computed T0 (adiabatic transition energy including zero-point energy correction) values, which agree well with the available experimental T0 value much better than previously computed values and values computed with other MR methods in this work. In addition, the potential energy surfaces of the X(1)A(') and A(1)A(") states of HAsO were computed using the MRCI-F12 method. Franck-Condon factors between the two states, which include anharmonicity and Duschinsky rotation, were then computed and used to simulate the recently reported SVL emission spectra of HAsO and DAsO [R. Grimminger and D. J. Clouthier, J. Chem. Phys. 135, 184308 (2011)]. Our simulated SVL emission spectra confirm the assignments of the molecular carrier, the electronic states involved, and the vibrational structures observed in the SVL emission spectra but suggest a loss of intensity in the reported experimental spectra at the low emission energy region almost certainly due to a loss of responsivity near the cutoff region (~800 nm) of the detector used. Computed and experimentally derived re (equilibrium) and/or r0 {the (0,0,0) vibrational level} geometries of the two states of HAsO are discussed. PMID- 27179481 TI - Structural and electronic properties of UnOm (n=1-3,m=1-3n) clusters: A theoretical study using screened hybrid density functional theory. AB - The structural and electronic properties of small uranium oxide clusters UnOm (n=1-3, m=1-3n) are systematically studied within the screened hybrid density functional theory. It is found that the formation of U-O-U bondings and isolated U-O bonds are energetically more stable than U-U bondings. As a result, no uranium cores are observed. Through fragmentation studies, we find that the UnOm clusters with the m/n ratio between 2 and 2.5 are very stable, hinting that UO2+x hyperoxides are energetically stable. Electronically, we find that the O-2p states always distribute in the deep energy range, and the U-5f states always distribute at the two sides of the Fermi level. The U-6d states mainly hybridize with the U-5f states in U-rich clusters, while hybridizing with O-2p states in O rich clusters. Our work is the first one on the screened hybrid density functional theory level studying the atomic and electronic properties of the actinide oxide clusters. PMID- 27179482 TI - Photoionisation study of Xe.CF4 and Kr.CF4 van-der-Waals molecules. AB - We report on photoionization studies of Xe.CF4 and Kr.CF4 van-der-Waals complexes produced in a supersonic expansion and detected using synchrotron radiation and photoelectron-photoion coincidence techniques. The ionization potential of CF4 is larger than those of the Xe and Kr atoms and the ground state of the Rg.CF4 (+) ion correlates with Rg(+) ((2)P3/2) + CF4. The onset of the Rg.CF4 (+) signals was found to be only ~0.2 eV below the Rg ionization potential. In agreement with experiment, complementary ab initio calculations show that vertical transitions originating from the potential minimum of the ground state of Rg.CF4 terminate at a part of the potential energy surfaces of Rg.CF4 (+), which are approximately 0.05 eV below the Rg(+) ((2)P3/2) + CF4 dissociation limit. In contrast to the neutral complexes, which are most stable in the face geometry, for the Rg.CF4 (+) ions, the calculations show that the minimum of the potential energy surface is in the vertex geometry. Experiments which have been performed only with Xe.CF4 revealed no Xe.CF4 (+) signal above the first ionization threshold of Xe, suggesting that the Rg.CF4 (+) ions are not stable above the first dissociation limit. PMID- 27179483 TI - Alignment of CH3F in para-H2 crystal studied by IR quantum cascade laser polarization spectroscopy. AB - In order to investigate the alignment of CH3F in para-H2 crystals, high resolution polarization spectroscopy of the nu3 vibrational band is studied using a quantum cascade laser at 1040 cm(-1). It is found that the main and satellite series of peaks in the nu3 vibrational band of CH3F have the same polarization dependence. This result supports the previously proposed cluster model with ortho H2 in first and second nearest neighbor sites. The observed polarization dependence function is well described by a simple six-axis void model in which CH3F is not aligned along the c-axis of the crystal but tilted to 64.9(3) degrees from it. PMID- 27179484 TI - Femtosecond stimulated Raman spectroscopy as a tool to detect molecular vibrations in ground and excited electronic states. AB - We give a detailed theoretical analysis of the simplest variant of femtosecond stimulated Raman spectroscopy, where a picosecond Raman pump pulse and a femtosecond Raman probe pulse are applied resonantly to a chromophore in thermal equilibrium in the ground electronic state. We demonstrate that this technique is capable of the detection of dephasing-free Raman-like lines revealing vibrational modes not only in the electronic ground state but also in the excited electronic state of the chromophore. The analytical results obtained with simplifying assumptions for the shape of the laser pulses are substantiated by numerical simulations with realistic laser pulses, employing the equation-of-motion phase matching approach. PMID- 27179485 TI - Millimeter-wave spectroscopy of CrC (X(3)Sigma(-)) and CrCCH (X (6)Sigma(+)): Examining the chromium-carbon bond. AB - Pure rotational spectroscopy of the CrC (X(3)Sigma(-)) and CrCCH (X (6)Sigma(+)) radicals has been conducted using millimeter/sub-millimeter direct absorption methods in the frequency range 225-585 GHz. These species were created in an AC discharge of Cr(CO)6 and either methane or acetylene, diluted in argon. Spectra of the CrCCD were also recorded for the first time using deuterated acetylene as the carbon precursor. Seven rotational transitions of CrC were measured, each consisting of three widely spaced, fine structure components, arising from spin spin and spin-rotation interactions. Eleven rotational transitions were recorded for CrCCH and five for CrCCD; each transition in these cases was composed of a distinct fine structure sextet. These measurements confirm the respective (3)Sigma(-) and (6)Sigma(+) ground electronic states of these radicals, as indicated from optical studies. The data were analyzed using a Hund's case (b) Hamiltonian, and rotational, spin-spin, and spin-rotation constants have been accurately determined for all three species. The spectroscopic parameters for CrC were significantly revised from previous optical work, while those for CrCCH are in excellent agreement; completely new constants were established for CrCCD. The chromium-carbon bond length for CrC was calculated to be 1.631 A, while that in CrCCH was found to be rCr-C = 1.993 A - significantly longer. This result suggests that a single Cr-C bond is present in CrCCH, preserving the acetylenic structure of the ligand, while a triple bond exists in CrC. Analysis of the spin constants suggests that CrC has a nearby excited (1)Sigma(+) state lying ~16 900 cm(-1) higher in energy, and CrCCH has a (6)Pi excited state with E ~ 4800 cm( 1). PMID- 27179486 TI - Bond energies of ThO(+) and ThC(+): A guided ion beam and quantum chemical investigation of the reactions of thorium cation with O2 and CO. AB - Kinetic energy dependent reactions of Th(+) with O2 and CO are studied using a guided ion beam tandem mass spectrometer. The formation of ThO(+) in the reaction of Th(+) with O2 is observed to be exothermic and barrierless with a reaction efficiency at low energies of k/kLGS = 1.21 +/- 0.24 similar to the efficiency observed in ion cyclotron resonance experiments. Formation of ThO(+) and ThC(+) in the reaction of Th(+) with CO is endothermic in both cases. The kinetic energy dependent cross sections for formation of these product ions were evaluated to determine 0 K bond dissociation energies (BDEs) of D0(Th(+)-O) = 8.57 +/- 0.14 eV and D0(Th(+)-C) = 4.82 +/- 0.29 eV. The present value of D0 (Th(+)-O) is within experimental uncertainty of previously reported experimental values, whereas this is the first report of D0 (Th(+)-C). Both BDEs are observed to be larger than those of their transition metal congeners, TiL(+), ZrL(+), and HfL(+) (L = O and C), believed to be a result of lanthanide contraction. Additionally, the reactions were explored by quantum chemical calculations, including a full Feller Peterson-Dixon composite approach with correlation contributions up to coupled cluster singles and doubles with iterative triples and quadruples (CCSDTQ) for ThC, ThC(+), ThO, and ThO(+), as well as more approximate CCSD with perturbative (triples) [CCSD(T)] calculations where a semi-empirical model was used to estimate spin-orbit energy contributions. Finally, the ThO(+) BDE is compared to other actinide (An) oxide cation BDEs and a simple model utilizing An(+) promotion energies to the reactive state is used to estimate AnO(+) and AnC(+) BDEs. For AnO(+), this model yields predictions that are typically within experimental uncertainty and performs better than density functional theory calculations presented previously. PMID- 27179487 TI - Heterogeneous and hyperfine interactions between valence states of molecular iodine correlating with the I((2)P1/2) + I((2)P1/2) dissociation limit. AB - Detailed analysis of interactions between all 0g (+), 1u, and 0u (-) weakly bound states of iodine molecule correlating with the I((2)P1/2) + I((2)P1/2) (bb) dissociation limit has been performed. For this purpose, the 0u (-) (bb) state has been described using analysis of rotationally resolved excitation spectra of luminescence from the g0g (-) state populated in a three-step three-color perturbation facilitated excitation scheme via the 0u (-) state. Energies of 41 rovibrational levels, molecular constants, and potential energy curve have been determined. Energy gaps between closest rovibrational levels of the 0u (-) and 0g (+), 1u (bb) states are found to be large, ~6 cm(-1). However, interaction of all three 0g (+), 1u, and 0u (-) (bb) states has been observed. It has been found that the 0u (-) and 1u electronic states are mixed by heterogeneous interactions, while their mixing with the 0g (+) one is due to hyperfine interactions predominantly. Admixture coefficients and electronic matrix elements of the coupling between the 0g (+) ~1u, 0g (+)~0u (-), and 0u (-) ~1u states have been estimated. PMID- 27179488 TI - UV + V UV double-resonance studies of autoionizing Rydberg states of the hydroxyl radical. AB - The hydroxyl radical (OH) is a key oxidant in atmospheric and combustion chemistry. Recently, a sensitive and state-selective ionization method has been developed for detection of the OH radical that utilizes UV excitation on the A(2)Sigma(+)-X(2)Pi transition followed by fixed 118 nm vacuum ultraviolet (VUV) radiation to access autoionizing Rydberg states [J. M. Beames et al., J. Chem. Phys. 134, 241102 (2011)]. The present study uses tunable VUV radiation generated by four-wave mixing to examine the origin of the enhanced ionization efficiency observed for OH radicals prepared in specific A(2)Sigma(+) intermediate levels. The enhancement is shown to arise from resonant excitation to distinct rotational and fine structure levels of two newly identified (2)Pi Rydberg states with an A(3)Pi cationic core and a 3d electron followed by ionization. Spectroscopic constants are derived and effects due to uncoupling of the Rydberg electron are revealed for the OH (2)Pi Rydberg states. The linewidths indicate a Rydberg state lifetime due to autoionization on the order of a picosecond. PMID- 27179489 TI - Dynamic and temperature dependent response of physical vapor deposited Se in freely standing nanometric thin films. AB - Here, we report results from an investigation of nano-scale size or confinement effects on the glass transition and viscoelastic properties of physical vapor deposited selenium films. The viscoelastic response of freely standing Se films was determined using a biaxial membrane inflation or bubble inflation method [P. A. O'Connell and G. B. McKenna, Science 307, 1760-1763 (2005)] on films having thicknesses from 60 to 267 nm and over temperatures ranging from Tg, macroscopic 15 degrees C to Tg, macroscopic + 21 degrees C. Time-temperature superposition and time-thickness superposition were found to hold for the films in the segmental dispersion. The responses are compared with macroscopic creep and recoverable creep compliance data for selenium [K. M. Bernatz et al., J. Non Cryst. Solids 307, 790-801 (2002)]. The time-temperature shift factors for the thin films show weaker temperature dependence than seen in the macroscopic behavior, being near to Arrhenius-like in their temperature dependence. Furthermore, the Se films exhibit a "rubbery-like" stiffening that increases as film thickness decreases similar to prior observations [P. A. O'Connell et al., Macromolecules 45(5), 2453-2459 (2012)] for organic polymers. In spite of the differences from the macroscopic behavior in the temperature dependence of the viscoelastic response, virtually no change in Tg as determined from the thickness dependence of the retardation time defining Tg was observed in the bubble inflation creep experiments to thicknesses as small as 60 nm. We also find that the observed rubbery stiffening is consistent with the postulate of K. L. Ngai et al. [J. Polym. Sci., Part B: Polym. Phys. 51(3), 214-224 (2013)] that it should correlate with the change of the macroscopic segmental relaxation. PMID- 27179490 TI - Simulated conduction rates of water through a (6,6) carbon nanotube strongly depend on bulk properties of the model employed. AB - We investigate pressure driven flow rates of water through a (6,6) carbon nanotube (CNT) for the TIP3P, SPC/E, and TIP4P/2005 water models. The flow rates are shown to be strongly model dependent, differing by factors that range from ~6 to ~2 as the temperature varies from 260 to 320 K, with TIP3P showing the fastest flow and TIP4P/2005 the slowest. For the (6,6) CNT, the size constraint allows only single-file conduction for all three water models. Hence, unlike the situation for the larger [(8,8) and (9,9)] CNTs considered in our earlier work [L. Liu and G. N. Patey, J. Chem. Phys. 141, 18C518 (2014)], the different flow rates cannot be attributed to different model-dependent water structures within the nanotubes. By carefully examining activation energies, we trace the origin of the model discrepancies for the (6,6) CNT to differing rates of entry into the nanotube, and these in turn are related to differing bulk mobilities of the water models. Over the temperature range considered, the self-diffusion coefficients of the TIP3P model are much larger than those of TIP4P/2005 and those of real water. Additionally, we show that the entry rates are approximately inversely proportional to the shear viscosity of the bulk liquid, in agreement with the prediction of continuum hydrodynamics. For purposes of comparison, we also consider the larger (9,9) CNT. In the (9,9) case, the flow rates for the TIP3P model still appear to be mainly controlled by the entry rates. However, for the SPC/E and TIP4P/2005 models, entry is no longer the rate determining step for flow. For these models, the activation energies controlling flow are considerably larger than the energetic barriers to entry, due in all likelihood to the ring like water clusters that form within the larger nanotube. PMID- 27179491 TI - Isotope effect on hydrated electron relaxation dynamics studied with time resolved liquid jet photoelectron spectroscopy. AB - The excited state relaxation dynamics of the solvated electron in H2O and D2O are investigated using time-resolved photoelectron spectroscopy in a liquid microjet. The data show that the initial excited state decays on a time scale of 75 +/- 12 fs in H2O and 102 +/- 8 fs in D2O, followed by slower relaxation on time scales of 400 +/- 70 fs and 390 +/- 70 fs that are isotopically invariant within the precision of our measurements. Based on the time evolution of the transient signals, the faster and slower time constants are assigned to p -> s internal conversion (IC) of the hydrated electron and relaxation on the ground electronic state, respectively. This assignment is consistent with the non-adiabatic mechanism for relaxation of the hydrated electron and yields an isotope effect of 1.4 +/- 0.2 for IC of the hydrated electron. PMID- 27179492 TI - Solvent organization around the perfluoro group of coumarin 153 governs its photophysical properties: An experimental and simulation study of coumarin dyes in ethanol as well as fluorinated ethanol solvents. AB - The self-aggregation property of the perfluoro group containing molecules makes it important in the research fields of biology and polymer and organic synthesis. In the quest of understanding the role of the perfluoro group on the photophysical properties of perfluoro-containing molecules in biologically important fluoroethanol solvents, we have applied photophysical as well as molecular dynamics simulation techniques to explore the properties of perfluoro groups containing molecule coumarin-153 (C153) in ethanol (ETH), monofluoroethanol (MFE), difluoroethanol (DFE), and trifluoroethanol (TFE) and compared them with the molecules without perfluoro moiety, namely coumarin-6H (C6H) and coumarin-480 (C480). In contrast to C6H and C480, the excited state lifetime of C153 in fluorinated ETHs is not monotonic. The excited state lifetime of C153 decreases in MFE and DFE as compared to ETH, whereas in TFE, it increases as compared to MFE and DFE. Molecular dynamics simulation reveals that the carbon terminal away from the OH group of fluorinated ETHs has a preferential orientation near the perfluoro (CF3) group of C153. In MFE and DFE, the CF3 group of C153 prefers to have a CF2-F?H -(CHF) type of electrostatic interaction over CF2-F?F -(CH2) kind of dispersion interaction which increases the rate of nonradiative decay, probably due to the electrostatic nature of the CF2-F?H (CHF) hydrogen bond. On the other hand, in TFE, C-F? F-C type of dispersion interaction, also known as fluorous interaction, takes place between the CF3 groups of C153 and TFE which decreases the rate of nonradiative rate as compared to MFE and DFE, leading to the increased lifetime of C153 in TFE. Photophysical and MD simulation studies clearly depict that the structural organization of solvents and their interaction with the fluorocarbon group are crucial factors for the photophysical behavior of the fluorocarbon containing molecules. PMID- 27179493 TI - Temperature of maximum density and excess thermodynamics of aqueous mixtures of methanol. AB - In this work, we present a study of representative excess thermodynamic properties of aqueous mixtures of methanol over the complete concentration range, based on extensive computer simulation calculations. In addition to test various existing united atom model potentials, we have developed a new force-field which accurately reproduces the excess thermodynamics of this system. Moreover, we have paid particular attention to the behavior of the temperature of maximum density (TMD) in dilute methanol mixtures. The presence of a temperature of maximum density is one of the essential anomalies exhibited by water. This anomalous behavior is modified in a non-monotonous fashion by the presence of fully miscible solutes that partly disrupt the hydrogen bond network of water, such as methanol (and other short chain alcohols). In order to obtain a better insight into the phenomenology of the changes in the TMD of water induced by small amounts of methanol, we have performed a new series of experimental measurements and computer simulations using various force fields. We observe that none of the force-fields tested capture the non-monotonous concentration dependence of the TMD for highly diluted methanol solutions. PMID- 27179494 TI - Enhancement of the droplet nucleation in a dense supersaturated Lennard-Jones vapor. AB - The vapor-liquid nucleation in a dense Lennard-Jones system is studied analytically and numerically. A solution of the nucleation kinetic equations, which includes the elementary processes of condensation/evaporation involving the lightest clusters, is obtained, and the nucleation rate is calculated. Based on the equation of state for the cluster vapor, the pre-exponential factor is obtained. The latter diverges as a spinodal is reached, which results in the nucleation enhancement. The work of critical cluster formation is calculated using the previously developed two-parameter model (TPM) of small clusters. A simple expression for the nucleation rate is deduced and it is shown that the work of cluster formation is reduced for a dense vapor. This results in the nucleation enhancement as well. To verify the TPM, a simulation is performed that mimics a steady-state nucleation experiments in the thermal diffusion cloud chamber. The nucleating vapor with and without a carrier gas is simulated using two different thermostats for the monomers and clusters. The TPM proves to match the simulation results of this work and of other studies. PMID- 27179495 TI - A hybrid-exchange density functional study of the bonding and electronic structure in bulk CuFeS2. AB - The geometric, electronic, and magnetic properties of bulk chalcopyrite CuFeS2 have been investigated using hybrid-exchange density functional theory calculations. The results are compared with available theoretical and experimental data. The theoretical description of the bonding and electronic structure in CuFeS2 is analyzed in detail and compared to those computed for chalcocite (CuS2) and greigite (Fe3S4). In particular, the behavior of the 3d electrons of Fe(3+) is discussed in terms of the Hubbard-Anderson model in the strongly correlated regime and found to be similarly described in both materials by an on-site Coulomb repulsion (U) of ~8.9 eV and a transfer integral (t) of ~0.3 eV. PMID- 27179496 TI - On the theory of electric double layer with explicit account of a polarizable co solvent. AB - We present a continuation of our theoretical research into the influence of co solvent polarizability on a differential capacitance of the electric double layer. We formulate a modified Poisson-Boltzmann theory, using the formalism of density functional approach on the level of local density approximation taking into account the electrostatic interactions of ions and co-solvent molecules as well as their excluded volume. We derive the modified Poisson-Boltzmann equation, considering the three-component symmetric lattice gas model as a reference system and minimizing the grand thermodynamic potential with respect to the electrostatic potential. We apply present modified Poisson-Boltzmann equation to the electric double layer theory, showing that accounting for the excluded volume of co-solvent molecules and ions slightly changes the main result of our previous simplified theory. Namely, in the case of small co-solvent polarizability with its increase under the enough small surface potentials of electrode, the differential capacitance undergoes the significant growth. Oppositely, when the surface potential exceeds some threshold value (which is slightly smaller than the saturation potential), the increase in the co-solvent polarizability results in a differential capacitance decrease. However, when the co-solvent polarizability exceeds some threshold value, its increase generates a considerable enhancement of the differential capacitance in a wide range of surface potentials. We demonstrate that two qualitatively different behaviors of the differential capacitance are related to the depletion and adsorption of co solvent molecules at the charged electrode. We show that an additive of the strongly polarizable co-solvent to an electrolyte solution can shift significantly the saturation potential in two qualitatively different manners. Namely, a small additive of strongly polarizable co-solvent results in a shift of saturation potential to higher surface potentials. On the contrary, a sufficiently large additive of co-solvent shifts the saturation potential to lower surface potentials. We obtain that an increase in the co-solvent polarizability makes the electrostatic potential profile longer-ranged. However, increase in the co-solvent concentration in the bulk leads to non-monotonic behavior of the electrostatic potential profile. An increase in the co-solvent concentration in the bulk at its sufficiently small values makes the electrostatic potential profile longer-ranged. Oppositely, when the co-solvent concentration in the bulk exceeds some threshold value, its further increase leads to decrease in electrostatic potential at all distances from the electrode. PMID- 27179497 TI - Graphene oxide and adsorption of chloroform: A density functional study. AB - Chlorinated hydrocarbon compounds are of environmental concerns, since they are toxic to humans and other mammals, and are widespread, and exposure is hard to avoid. Understanding and improving methods to reduce the amount of the substances are important. We present an atomic-scale calculational study of the adsorption of chlorine-based substance chloroform (CHCl3) on graphene oxide, as a step in estimating the capacity of graphene oxide for filtering out such substances, e.g., from drinking water. The calculations are based on density functional theory, and the recently developed consistent-exchange functional for the van der Waals density-functional method is employed. We obtain values of the chloroform adsorption energy varying from roughly 0.2 to 0.4 eV per molecule. This is comparable to previously found results for chloroform adsorbed directly on clean graphene, using similar calculations. In a wet environment, like filters for drinking water, the graphene will not stay clean and will likely oxidize, and thus adsorption onto graphene oxide, rather than clean graphene, is a more relevant process to study. PMID- 27179498 TI - Active sites of ligand-protected Au25 nanoparticle catalysts for CO2 electroreduction to CO. AB - Recent experimental studies have reported the electrochemical reduction of carbon dioxide (CO2) into CO at atomically precise negatively charged Au25 (-) nanoclusters. The studies showed CO2 conversion at remarkably low overpotentials, but the exact mechanisms and nature of the active sites remain unclear. We used first-principles density functional theory and continuum solvation models to examine the role of the cluster during electrochemical CO2 reduction and analyze the free energies of proposed intermediate species. Contrary to previous assumptions, our results show that the fully ligand protected cluster is not an active CO2 reduction catalyst because formation of the crucial carboxyl intermediate required very high electrochemical potentials. Instead, our calculations suggest that the reduction process likely occurs on a dethiolated gold site, and adsorbed carboxyl intermediate formation was significantly stabilized at dethiolated gold sites. These findings point to the crucial role of exposed metal sites during electrochemical CO2 reduction at gold nanocluster catalysts. PMID- 27179499 TI - Dissociative adsorption of H2O on LiCoO2 (00l) surfaces: Co reduction induced by electron transfer from intrinsic defects. AB - Understanding the mechanism of the interaction of lithium ion conductors with water is crucial for both fundamental and technological points of view. Despite the generally accepted fact that water is one of main sources of the degradation of Li-ion recharge batteries, the physicochemical processes occurring at the water-lithium ion conductor interface are not fully understood. By using synchrotron X-ray photoelectron spectroscopy (SXPS) and O K- and Co L- X-ray absorption near edge structure (XANES), we evidence that H2O is dissociatively adsorbed on LiCoO2 thin film at room temperature resulting in the formation of OH groups and the accumulation of the negative charge at the surface accompanied by electron transfer to the initial empty Co3d (eg (*)) state. By considering the experimentally obtained energy diagram of the ionic conductor and water, direct charge transfer is not favorable due to a high difference in the chemical potential of the ionic conductor and electronic levels of the molecule. Here, we develop the model for the dissociative water adsorption which explains the electron transfer to LiCoO2 by using the atomistic approach. The model takes into account the intrinsic defects found on the surface (<2 nm depth) by using the depth resolved photoemission experiments and can be explored to other layered transition metal oxides to interpret the interaction of water with the surface of ionic conductors. PMID- 27179500 TI - Evaluation of molecular dynamics simulation methods for ionic liquid electric double layers. AB - We investigate how systematically increasing the accuracy of various molecular dynamics modeling techniques influences the structure and capacitance of ionic liquid electric double layers (EDLs). The techniques probed concern long-range electrostatic interactions, electrode charging (constant charge versus constant potential conditions), and electrolyte polarizability. Our simulations are performed on a quasi-two-dimensional, or slab-like, model capacitor, which is composed of a polarizable ionic liquid electrolyte, [EMIM][BF4], interfaced between two graphite electrodes. To ensure an accurate representation of EDL differential capacitance, we derive new fluctuation formulas that resolve the differential capacitance as a function of electrode charge or electrode potential. The magnitude of differential capacitance shows sensitivity to different long-range electrostatic summation techniques, while the shape of differential capacitance is affected by charging technique and the polarizability of the electrolyte. For long-range summation techniques, errors in magnitude can be mitigated by employing two-dimensional or corrected three dimensional electrostatic summations, which led to electric fields that conform to those of a classical electrostatic parallel plate capacitor. With respect to charging, the changes in shape are a result of ions in the Stern layer (i.e., ions at the electrode surface) having a higher electrostatic affinity to constant potential electrodes than to constant charge electrodes. For electrolyte polarizability, shape changes originate from induced dipoles that soften the interaction of Stern layer ions with the electrode. The softening is traced to ion correlations vertical to the electrode surface that induce dipoles that oppose double layer formation. In general, our analysis indicates an accuracy dependent differential capacitance profile that transitions from the characteristic camel shape with coarser representations to a more diffuse profile with finer representations. PMID- 27179501 TI - Mechanism and energetics of O and O2 adsorption on polar and non-polar ZnO surfaces. AB - Polar surfaces of semiconducting metal oxides can exhibit structures and chemical reactivities that are distinct from their non-polar surfaces. Using first principles calculations, we examine O adatom and O2 molecule adsorption on 8 different known ZnO reconstructions including Zn-terminated (Zn-ZnO) and O terminated (O-ZnO) polar surfaces, and non-polar surfaces. We find that adsorption tendencies are largely governed by the thermodynamic environment, but exhibit variations due to the different surface chemistries of various reconstructions. The Zn-ZnO surface reconstructions which appear under O-rich and H-poor environments are found to be most amenable to O and O2 adsorption. We attribute this to the fact that on Zn-ZnO, the O-rich environments that promote O adsorption also simultaneously favor reconstructions that involve adsorbed O species. On these Zn-ZnO surfaces, O2 dissociatively adsorbs to form O adatoms. By contrast, on O-ZnO surfaces, the O-rich conditions required for O or O2 adsorption tend to promote reconstructions involving adsorbed H species, making further O species adsorption more difficult. These insights about O2 adsorption on ZnO surfaces suggest possible design rules to understand the adsorption properties of semiconductor polar surfaces. PMID- 27179502 TI - Mode-selective chemistry on metal surfaces: The dissociative chemisorption of CH4 on Pt(111). AB - A quantum approach based on an expansion in vibrationally adiabatic eigenstates is used to explore CH4 dissociation on Pt(111). Computed sticking probabilities for molecules in the ground, 1v3 and 2v3, states are in very good agreement with the available experimental data, reproducing the variation in reactivity with collision energy and vibrational state. As was found in similar studies on Ni(100) and Ni(111), exciting the 1v1 symmetric stretch of CH4 is more effective at promoting the dissociative chemisorption of CH4 than exciting the 1v3 antisymmetric stretch. This behavior is explained in terms of symmetry, mode softening, and nonadiabatic transitions between vibrationally adiabatic states. We find that the efficacies of the bending modes for promoting reaction are reasonably large, and similar to the 1v3 state. The vibrational efficacies for promoting reaction on Ni(111) are larger than for reaction on Pt(111), due to the larger nonadiabatic couplings. Our computed sticking probabilities are in good agreement with results from recent ab initio molecular dynamics and reactive force field studies. PMID- 27179504 TI - Polymer gels with associating side chains and their interaction with surfactants. AB - Conformational behaviour of hydrophobically modified (HM) polymer gels in solutions of nonionic surfactants is studied theoretically. A HM gel contains hydrophobic side chains (stickers) grafted to its subchains. Hydrophobic stickers are capable to aggregate into joint micelles with surfactant molecules. Micelles containing more than one sticker serve as additional physical cross-links of the network, and their formation causes gel shrinking. In the proposed theoretical model, the interior of the gel/surfactant complex is treated as an array of densely packed spherical polymer brushes consisting of gel subchains tethered to the surface of the spherical sticker/surfactant micelles. Effect of stickers length and grafting density, surfactant concentration and hydrophobicity on gel swelling as well as on hydrophobic association inside it is analyzed. It is shown that increasing surfactant concentration can result in a gel collapse, which is caused by surfactant-induced hydrophobic aggregation of stickers, and a successive gel reswelling. The latter should be attributed to a growing fraction of surfactants in joint aggregates and, hence, increasing number of micelles containing only one sticker and not participating in gel physical cross-linking. In polyelectrolyte (PE) gels hydrophobic aggregation is opposed by osmotic pressure of mobile counterions, so that at some critical ionization degree hydrophobic association is completely suppressed. Hydrophobic modification of polymers is shown to open new ways for controlling gel responsiveness. In particular, it is discussed that incorporation of photosensitive groups into gel subchains and/or surfactant tail could give a possibility to vary the gel volume by light. Since hydrophobic aggregation regularities in gels and solutions are common, we hope our findings will be useful for design of polymer based self healing materials as well. PMID- 27179503 TI - Lipid-assisted protein transport: A diffusion-reaction model supported by kinetic experiments and molecular dynamics simulations. AB - The protein transport inside a cell is a complex phenomenon that goes through several difficult steps. The facilitated transport requires sophisticated machineries involving protein assemblies. In this work, we developed a diffusion reaction model to simulate co-transport kinetics of proteins and lipids. We assume the following: (a) there is always a small lipid concentration of order of the Critical Micellar Concentration (CMC) in equilibrium with the membrane; (b) the binding of lipids to proteins modulates the hydrophobicity of the complexes and, therefore, their ability to interact and merge with the bilayer; and (c) some lipids leave the bilayer to replenish those bound to proteins. The model leads to a pair of integral equations for the time-evolution of the adsorbed proteins in the lipid bilayer. Relationships between transport kinetics, CMC, and lipid-protein binding constants were found. Under particular conditions, a perturbation analysis suggests the onset of kinks in the protein adsorption kinetics. To validate our model, we performed leakage measurements of vesicles composed by either high or low CMC lipids interacting with Islet Amyloid PolyPeptide (IAPP) and Abeta (1-40) used as sample proteins. Since the lipid protein complex stoichiometry is not easily accessible, molecular dynamics simulations were performed using monomeric IAPP interacting with an increasing number of phospholipids. Main results are the following: (a) 1:1 lipid-protein complexes generally show a faster insertion rate proportional to the complex hydrophobicity and inversely related to lipid CMC; (b) on increasing the number of bound lipids, the protein insertion rate decreases; and PMID- 27179505 TI - Thermophoretically induced large-scale deformations around microscopic heat centers. AB - Selectively heating a microscopic colloidal particle embedded in a soft elastic matrix is a situation of high practical relevance. For instance, during hyperthermic cancer treatment, cell tissue surrounding heated magnetic colloidal particles is destroyed. Experiments on soft elastic polymeric matrices suggest a very long-ranged, non-decaying radial component of the thermophoretically induced displacement fields around the microscopic heat centers. We theoretically confirm this conjecture using a macroscopic hydrodynamic two-fluid description. Both thermophoretic and elastic effects are included in this theory. Indeed, we find that the elasticity of the environment can cause the experimentally observed large-scale radial displacements in the embedding matrix. Additional experiments confirm the central role of elasticity. Finally, a linearly decaying radial component of the displacement field in the experiments is attributed to the finite size of the experimental sample. Similar results are obtained from our theoretical analysis under modified boundary conditions. PMID- 27179506 TI - Multi-layer multi-configuration time-dependent Hartree (ML-MCTDH) approach to the correlated exciton-vibrational dynamics in the FMO complex. AB - The coupled quantum dynamics of excitonic and vibrational degrees of freedom is investigated for high-dimensional models of the Fenna-Matthews-Olson complex. This includes a seven- and an eight-site model with 518 and 592 harmonic vibrational modes, respectively. The coupling between local electronic transitions and vibrations is described within the Huang-Rhys model using parameters that are obtained by discretization of an experimental spectral density. Different pathways of excitation energy flow are analyzed in terms of the reduced one-exciton density matrix, focussing on the role of vibrational and vibronic excitations. Distinct features due to both competing time scales of vibrational and exciton motion and vibronically assisted transfer are observed. The question of the effect of initial state preparation is addressed by comparing the case of an instantaneous Franck-Condon excitation at a single site with that of a laser field excitation. PMID- 27179507 TI - Criteria for folding in structure-based models of proteins. AB - In structure-based models of proteins, one often assumes that folding is accomplished when all contacts are established. This assumption may frequently lead to a conceptual problem that folding takes place in a temperature region of very low thermodynamic stability, especially when the contact map used is too sparse. We consider six different structure-based models and show that allowing for a small, but model-dependent, percentage of the native contacts not being established boosts the folding temperature substantially while affecting the time scales of folding only in a minor way. We also compare other properties of the six models. We show that the choice of the description of the backbone stiffness has a substantial effect on the values of characteristic temperatures that relate both to equilibrium and kinetic properties. Models without any backbone stiffness (like the self-organized polymer) are found to perform similar to those with the stiffness, including in the studies of stretching. PMID- 27179508 TI - Erratum: "Thermodynamic perturbation theory for associating fluids confined in a one-dimensional pore" [J. Chem. Phys. 142, 234906 (2015)]. PMID- 27179509 TI - Surveillance and response systems for elimination of tropical diseases: summary of a thematic series in Infectious Diseases of Poverty. AB - The peer-reviewed journal Infectious Diseases of Poverty provides a new platform to engage with, and disseminate in an open-access format, science outside traditional disciplinary boundaries. The current piece reviews a thematic series on surveillance-response systems for elimination of tropical diseases. Overall, 22 contributions covering a broad array of diseases are featured - i.e. clonorchiasis, dengue, hepatitis, human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), H7N9 avian influenza, lymphatic filariasis, malaria, Middle East respiratory syndrome (MERS), rabies, schistosomiasis and tuberculosis (TB). There are five scoping reviews, a commentary, a letter to the editor, an opinion piece and an editorial pertaining to the theme "Elimination of tropical disease through surveillance and response". The remaining 13 articles are original contributions mainly covering (i) drug resistance; (ii) innovation and validation in the field of mathematical modelling; (iii) elimination of infectious diseases; and (iv) social media reports on disease outbreak notifications released by national health authorities. Analysis of the authors' affiliations reveals that scientists from the People's Republic of China (P.R. China) are prominently represented. Possible explanations include the fact that the 2012 and 2014 international conferences pertaining to surveillance-response mechanisms were both hosted by the National Institute of Parasitic Diseases (NIPD) in Shanghai, coupled with P.R. China's growing importance with regard to the control of infectious diseases. Within 4 to 22 months of publication, three of the 22 contributions were viewed more than 10 000 times each. With sustained efforts focusing on relevant and strategic information towards control and elimination of infectious diseases, Infectious Diseases of Poverty has become a leading journal in the field of surveillance and response systems in infectious diseases and beyond. PMID- 27179510 TI - Is venous congestion associated with reduced cerebral oxygenation and worse neurological outcome after cardiac arrest? AB - BACKGROUND: Post-cardiac arrest (CA) patients are at risk of secondary ischemic damage in the case of suboptimal brain oxygenation during an ICU stay. We hypothesized that elevated central venous pressures (CVP) would impair cerebral perfusion and oxygenation (venous cerebral congestion). The aim of the present study was to investigate the relationship between CVP, cerebral tissue oxygen saturation (SctO2) as assessed with near-infrared spectroscopy (NIRS) and outcome in post-CA patients. METHODS: This was an observational study in 48 post-CA patients with continuous CVP and SctO2 monitoring during therapeutic hypothermia. RESULTS: The relationship between CVP and mean SctO2 was best described by an S shaped, third-degree polynomial regression curve (SctO2 = -0.002 * CVP(3) + 0.08 * CVP(2) - 1.07 * CVP + 69.78 %, R (2) 0.89, n = 1,949,108 data points) with high CVP (>20 mmHg) being associated with cerebral desaturation. Multivariate linear regression revealed CVP to be a more important determinant of SctO2 than mean arterial pressure (MAP) without important interaction between both (SctO2 = 0.01 * MAP - 0.20 * CVP + 0.001 * MAP * CVP + 65.55 %). CVP and cardiac output were independent determinants of SctO2 with some interaction between both (SctO2 = 1.86 * CO - 0.09 * CVP - 0.05 * CO * CVP + 60.04 %). Logistic regression revealed that a higher percentage of time with CVP above 5 mmHg was associated with lower chance of survival with a good neurological outcome (cerebral performance category (CPC) 1-2) at 180 days (OR 0.96, 95 % CI 0.92-1.00, p = 0.04). In a multivariate model, the negative association between CVP and outcome persisted after correction for hemodynamic variables, including ejection fraction and MAP. CONCLUSIONS: Elevated CVP results in lower brain saturation and is associated with worse outcome in post-CA patients. This pilot study provides support that venous cerebral congestion as indicated by high CVP may be detrimental for post CA patients. PMID- 27179511 TI - Combinatory effect of BRCA1 and HERC2 expression on outcome in advanced non-small cell lung cancer. AB - BACKGROUND: BRCA1 is a main component of homologous recombination and induces resistance to platinum in preclinical models. It has been studied as a potential predictive marker in lung cancer. Several proteins modulate the function of BRCA1. The E3 ubiquitin ligase HERC2 facilitates the assembly of the RNF8-UBC13 complex to recruit BRCA1 to DNA damage sites. The combined analysis of multiple components of the pathway leading to the recruitment of BRCA1 at DNA damage sites has the potentiality to improve the BRCA1 predictive model. METHODS: We retrospectively analyzed 71 paraffin-embedded tumor samples from advanced non small-cell lung cancer patients treated with first-line platinum based chemotherapy and measured the mRNA expression levels of BRCA1, RNF8, UBC13 and HERC2 using real-time PCR. The mRNA expression was categorized using median value as cut-off point. RESULTS: The median progression-free survival of all 71 patients was 7.2 months whereas the median overall survival of the study population was 10.7 months. Among patients with low BRCA1 expression, the median PFS was 7.4 months in the presence of low HERC2 levels and 5.9 months for patients expressing high HERC2 levels (p = 0.01). The median OS was 15.3 months for patients expressing low levels of both genes and 7.4 months for those with low BRCA1 but high HERC2 (p = 0.008). The multivariate analysis showed that among patients with Eastern Cooperative Oncology Group performance status 0-1, the combined low expression of both BRCA1 and HERC2 clearly reduced the risk of progression (p = 0.03) and of death (p = 0.004). CONCLUSIONS: These findings confirm the potentiality of integrated DNA repair components analysis in predicting the sensitivity to platinum in lung cancer. The study indicates a predictive role for HERC2 mRNA expression and paves the way for further refinement of the BRCA1 predictive model. PMID- 27179514 TI - Review of Handbook of Secure Care : Edited by Geoffrey Dickens, Philip Sugarman, Marco Picchioni. PMID- 27179512 TI - Undifferentiated sarcoma originating from the mitral valve: a case report. AB - BACKGROUND: Primary cardiac sarcomas are quite uncommon. Among them, sarcomas originating from the mitral valve are exceedingly rare. They are often misdiagnosed due to non-specific symptoms. The prognosis of cardiac sarcomas remains poor, and finding a more effective therapy poses a big challenge for the doctors. Currently, complete surgical resection of the tumor is still the most popular treatment in cases that without metastases. CASE PRESENTATION: A 38-year old female was transported to our department with persistent cough and chest pain. The operation of mitral valve replacement was scheduled after a provisional diagnosis of serious mitral stenosis. During the operation, we found that a large polypoid mass infiltrating mainly the mitral valve and part of the left atria. We removed the tumor as completely as possible and replaced the mitral valve. Histology confirmed the diagnosis of undifferentiated sarcoma after operation. The patient was asymptomatic with no recurrence at 3-month follow-up. CONCLUSION: Primary cardiac sarcomas is a rare and the prognosis is poor. The sarcomas is often found by chance during the operation. Surgical operation need to be carried out directly. PMID- 27179513 TI - Avoiding the distant elephant: a model to approach the research component of specialization. PMID- 27179515 TI - Enhanced Production of Recombinant Thermobifida fusca Isoamylase in Escherichia coli MDS42. AB - Isoamylase, an industrially significant enzyme used primarily in the saccharification of starch, is commonly obtained through recombinant expression in Escherichia coli. To improve the yield of this important enzyme, the isoamylase from Thermobifida fusca was expressed in the reduced-genome E. coli strain MDS42. Expression conditions were initially optimized in shake flasks. The optimal induction temperature was 37 degrees C and IPTG was superior to lactose as an inducer due to the low intracellular beta-galactosidase activity in E. coli MDS42 expression system. Then, expression conditions were optimized in a 3.6-L fermenter. In the fermenter, optimal isoamylase expression was obtained when cells were grown at 37 degrees C and expression was induced at mid-log phase using 0.25 mM IPTG. The greatest isoamylase activity (22,983.0 U/mL of culture) and production (18.8 mg/mL) were obtained 24 h after induction of expression. These values are the highest ever reported, suggesting that E. coli MDS42 is a suitable host for the production of enzymes for industrial use. PMID- 27179516 TI - Optimization of High Solids Dilute Acid Hydrolysis of Spent Coffee Ground at Mild Temperature for Enzymatic Saccharification and Microbial Oil Fermentation. AB - Soluble coffee, being one of the world's most popular consuming drinks, produces a considerable amount of spent coffee ground (SCG) along with its production. The SCG could function as a potential lignocellulosic feedstock for production of bioproducts. The objective of this study is to investigate the possible optimal condition of dilute acid hydrolysis (DAH) at high solids and mild temperature condition to release the reducing sugars from SCG. The optimal condition was found to be 5.3 % (w/w) sulfuric acid concentration and 118 min reaction time. Under the optimal condition, the mean yield of reducing sugars from enzymatic saccharification of defatted SCG acid hydrolysate was 563 mg/g. The SCG hydrolysate was then successfully applied to culture Lipomyces starkeyi for microbial oil fermentation without showing any inhibition. The results suggested that dilute acid hydrolysis followed by enzymatic saccharification has the great potential to convert SCG carbohydrates to reducing sugars. This study is useful for the further developing of biorefinery using SCG as feedstock at a large scale. PMID- 27179517 TI - Antimicrobial Potential of Callistemon lanceolatus Seed Extract and its Statistical Optimization. AB - Plants have always been eminent source of medicinal products. Screening of the aqueous seeds extract of Callistemon lanceolatus (bottle brush) revealed its broad spectrum antimicrobial potential with an inhibition zone ranging from 13 to 28 mm against various pathogenic microorganisms. While optimizing the different parameters the antimicrobial activity was better expressed at 15 % concentration, prepared by extracting the material at 60 degrees C for 20 min. The extract was filtered through muslin cloth and gave best results at its natural pH. Statistical optimization by Response surface methodology enhanced the antimicrobial activity up to 1.6-fold. Minimum inhibitory concentration values of the aqueous extract of seeds of C. lanceolatus against different organisms ranged from 1-5 mg/ml. The viable cell count studies indicated a bactericidal effect against most of the pathogens. The aqueous extract was found to be relatively thermostable at 100 degrees C. When treated for shelf life at ambient conditions and refrigeration temperature (2-8 degrees C), the latter only showed a 28 % loss in antimicrobial activity. The aqueous extract was found to be biosafe when evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide reagent (MTT toxicity) assay and Ames mutagenicity assay. PMID- 27179518 TI - Purification and Immobilization of a Novel Enantioselective Lipase from Tsukamurella tyrosinosolvents for Efficient Resolution of Ethyl 2-(2 oxopyrrolidin-1-yl) Butyrate. AB - A highly enantioselective lipase from Tsukamurella tyrosinosolvents E105 was purified via ultrasonic extraction, precipitation, and chromatographic steps. The enzyme was purified about 38-fold with the recovery yield of 9 % and was confirmed as a dimer protein consisting of two identical subunits with a molecular mass of 24 kDa. The purified lipase was used to catalyze resolution of racemic ethyl 2-(2-oxopyrrolidin-1-yl) butyrate to (S)-2-(2-oxopyrrolidin-1-yl) butyric acid. The maximum activity of such lipase was obtained at pH 7.5, 35 degrees C, and the highest relative activity (156.80 %) was observed in the presence of 0.5 mM Co2+. Subsequently, the lipase was encapsulated within a mixture of 3 % sodium alginate and 0.8 % carrageenan, and then cross-linked with 0.6 % glutaraldehyde to enhance its biocatalytic capability and stability. Comparing with 36.9 % product yield and 97.5 % product ee of free lipase, the highest product yield of 46.3 % and ee of 98.5 % for immobilized lipase were achieved with the presence of 20 mM substrate. In addition, the reusability of immobilized lipase was also investigated, which could maintain 63.7 % of its initial conversion yield after seven repeated batch reactions. Thus, the evaluated enantioselective lipase in this work has a good potential for further industrial application. PMID- 27179519 TI - Formal Nutritional Education Improves Weight Loss in Bariatric Patients Following Laparoscopic Sleeve Gastrectomy. AB - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is an increasingly performed procedure in the bariatric surgery armamentarium. This study evaluates our experience with LSG at Dwight D. Eisenhower Army Medical Center (DDEAMC) during the time period of 2008-2010. We found that the inclusion of formal nutritional education significantly increased our weight loss results following LSG. METHODS: This is a retrospective review from our LSG caseload from 2008 to 2010. During that time, we performed 159 LSG. In our review, we performed comparative data of all operative years during 2008-2010 for up to 3 years postoperatively. Our main focus was in regard to weight loss as measured by percentage of excess body weight loss (%EWL), percentage of total weight loss (%TWL), and percentage of excess BMI loss (%EBL). We also evaluated the effect of LSG on diabetes mellitus (DM) and hypertension (HTN) postoperatively. RESULTS: We found an improvement in our %EWL, %TWL, and %EBL rates in our LSG cases following the inclusion of formal nutritional education. There was a mean increase in %EWL of 15 %, %TWL of 7 %, and %EBL of 21 %, which were statistically significant, that was present at all postoperative years of follow-up. We determined the only variable that changed in our bariatric program starting in 2010 was the inclusion of formal nutritional education. We also found a statistically significant improvement in resolution of HTN with the inclusion of formal nutritional education. CONCLUSIONS: The addition of formal nutritional education can enhance weight loss following bariatric surgery. We have shown a significant improvement in weight loss results following LSG with the implementation of formal nutritional education; this is the only study to our knowledge evaluating formal nutritional education and LSG. PMID- 27179520 TI - Quality of Life and Bariatric Surgery: Cross-Sectional Study and Analysis of Factors Influencing Outcome. AB - PURPOSE: The aims of our study were to compare quality of life (QOL) in obese patients after bariatric surgery with that in controls seeking surgery and to investigate which factors are associated with QOL in the Moorehead-Ardelt Quality of Life Questionnaire II (MA II). MATERIALS AND METHODS: This was a cross sectional study. The operated group consisted of patients after laparoscopic sleeve gastrectomy or laparoscopic Roux-en-Y gastric bypass. The MA II was administered by e-mail to 305 patients 12-18 months after surgery. The control groups consisted of 101 obese patients. We compared the QOL scores and considered good and very good outcomes to be satisfactory. Multiple logistic regression and correlation analysis was performed to identify factors associated with QOL. RESULTS: In the operated group, the total MA II score was 1.70 +/- 0.76, which was higher than 0.59 +/- 1.17 in the control group. The score adjusted for the type of surgery was comparable. The prevalence of satisfactory QOL outcomes was similar in both post-operative subgroups and was still higher than in the control group. We identified four factors associated with higher QOL in obese patients. Weight loss was not correlated with total score in MAII. CONCLUSIONS: This study demonstrates that patients after bariatric surgery have a higher score in MA II, which reflects better QOL. The scoring adjusted by type of operation is comparable. QOL among obese patients is dependent on age, gender, history of bariatric surgery, and partnered status. Body mass reduction was not associated with outcome in MAII. PMID- 27179522 TI - Genome-wide analysis of calcium-dependent protein kinases and their expression patterns in response to herbivore and wounding stresses in soybean. AB - Calcium-dependent protein kinases (CDPKs) play important roles in various aspects of plant physiology and involve in many cellular processes. However, genome-wide analysis of CDPK family in plant species is limited and few studies have been reported in soybean. In this study, a total of 39 genes encoding CDPKs were identified from the whole-genome sequence of soybean (Glycine max), which were denominated as GmCPK1-GmCPK39. These 39 CDPK genes could be classified into four subfamilies, and most genes showed tissue-specific expression patterns. Eight soybean CDPKs clustered together with the previously reported CDPKs related to pathogen, wounding, or herbivore stress were further analyzed. Differential gene expression analysis of these eight CDPK genes in response to herbivore and wounding stresses helps us identify GmCPK3 and GmCPK31 as the candidate genes for herbivore resistance in soybean, whose relative transcript abundance rapidly increased after wound and herbivore attacks. Sub-cellular localization revealed that GmCPK3 and GmCPK31 were localized in plasma membranes, which is consistent with previously reported plant defense related CDPKs. These results may suggest that GmCPK3 and GmCPK31 play important roles in the plant response to biotic stress. Simultaneously, our study will provide an important foundation for further functional characterization of the soybean CDPK gene family. PMID- 27179521 TI - The Youth Anxiety Measure for DSM-5 (YAM-5): Development and First Psychometric Evidence of a New Scale for Assessing Anxiety Disorders Symptoms of Children and Adolescents. AB - The Youth Anxiety Measure for DSM-5 (YAM-5) is a new self- and parent-report questionnaire to assess anxiety disorder symptoms in children and adolescents in terms of the contemporary classification system. International panels of childhood anxiety researchers and clinicians were used to construct a scale consisting of two parts: part one consists of 28 items and measures the major anxiety disorders including separation anxiety disorder, selective mutism, social anxiety disorder, panic disorder, and generalized anxiety disorder, whereas part two contains 22 items that focus on specific phobias and (given its overlap with situational phobias) agoraphobia. In general, the face validity of the new scale was good; most of its items were successfully linked to the intended anxiety disorders. Notable exceptions were the selective mutism items, which were frequently considered as symptoms of social anxiety disorder, and some specific phobia items especially of the natural environment, situational and other type, that were regularly assigned to an incorrect category. A preliminary investigation of the YAM-5 in non-clinical (N = 132) and clinically referred (N = 64) children and adolescents indicated that the measure was easy to complete by youngsters. In addition, support was found for the psychometric qualities of the measure: that is, the internal consistency was good for both parts, as well as for most of the subscales, the parent-child agreement appeared satisfactory, and there was also evidence for the validity of the scale. The YAM-5 holds promise as a tool for assessing anxiety disorder symptoms in children and adolescents. PMID- 27179523 TI - Functional Responses of Bacterioplankton Diversity and Metabolism to Experimental Bottom-Up and Top-Down Forcings. AB - We conducted an experimental approach using microcosms to simultaneously examine the functional response of natural freshwater bacterial assemblages to the impact of resources (nutrients) and top-down factors (viruses and grazers) on bacterial physiological state and their community structure. Addition of organic and inorganic nutrients led to the proliferation of high nucleic acid content bacterial cells accompanied by high bacterial growth efficiency (considered as proxy of bacterial carbon metabolism) estimates, suggesting that this subgroup represented the most active fraction of bacterial community and had a high capacity to incorporate carbon into its biomass. However, their rapid growth induced the pressure of viral lytic infection which led to their lysis toward the end of the experiment. In microcosms with flagellates plus viruses, and with viruses alone, the selective removal of metabolically active high nucleic acid cells through viral lysis benefitted the less active low nucleic acid content cells, perhaps via the use of lysis products for its growth and survival. Changes in bacterial physiological state in microcosms were reflected in their community structure which was examined using 16S ribosomal RNA (rRNA) gene sequencing by Illumina's Miseq platform. Chao estimator and Shannon diversity index values suggested that bacterial species richness was highest in the presence of both the top-down factors, indicating a tighter control of bacterioplankton dominants within a relatively stable bacterial community. The increase in bacterial metabolism with nutrient addition followed by subsequent lysis of bacterial dominants indicate that both resources and top-down factors work in concert for the sustenance of stable bacterial communities. PMID- 27179524 TI - Effect of Maternal Electroacupuncture on Perinatal Nicotine Exposure-Induced Lung Phenotype in Offspring. AB - INTRODUCTION: Pregnant women exposed to tobacco smoke predispose the offspring to many adverse consequences including an altered lung development and function. There is no effective therapeutic intervention to block the effects of smoke exposure on the developing lung. Clinical and animal studies demonstrate that acupuncture can modulate a variety of pathophysiological processes, including those involving the respiratory system; however, whether acupuncture affects the lung damage caused by perinatal smoke exposure is not known. METHODS: To determine the effect of acupuncture on perinatal nicotine exposure on the developing lung, pregnant rat dams were administered (1) saline, (2) nicotine, or (3) nicotine + electroacupuncture (EA). Nicotine was administered (1 mg/kg subcutaneously) once a day and EA was applied to both "Zusanli" (ST 36) points. Both interventions were administered from gestational day 6 to postnatal day 21 (PND21), following which pups were sacrificed. Lungs, blood, and brain were collected to examine markers of lung injury, repair, and hypothalamic pituitary adrenal (HPA) axis. RESULTS: Concomitant EA application blocked nicotine-induced changes in lung morphology, lung peroxisome proliferator-activated receptor gamma and wingless-int signaling, two key lung developmental signaling pathways, hypothalamic pituitary adrenal axis (hypothalamic corticotropic releasing hormone and lung glucocorticoid receptor levels), and plasma beta-endorphin levels. CONCLUSIONS: Electroacupuncture blocks the nicotine-induced changes in lung developmental signaling pathways and the resultant myogenic lung phenotype, known to be present in the affected offspring. We conclude that EA is a promising novel intervention against the smoke exposed lung damage to the developing lung. PMID- 27179525 TI - Identification and characterization of large DNA deletions affecting oil quality traits in soybean seeds through transcriptome sequencing analysis. AB - KEY MESSAGE: Identification and characterization of a 254-kb genomic deletion on a duplicated chromosome segment that resulted in a low level of palmitic acid in soybean seeds using transcriptome sequencing. A large number of soybean genotypes varying in seed oil composition and content have been identified. Understanding the molecular mechanisms underlying these variations is important for breeders to effectively utilize them as a genetic resource. Through design and application of a bioinformatics approach, we identified nine co-regulated gene clusters by comparing seed transcriptomes of nine soybean genotypes varying in oil composition and content. We demonstrated that four gene clusters in the genotypes M23, Jack and N0304-303-3 coincided with large-scale genome rearrangements. The co-regulated gene clusters in M23 and Jack mapped to a previously described 164 kb deletion and a copy number amplification of the Rhg1 locus, respectively. The coordinately down-regulated gene clusters in N0304-303-3 were caused by a 254-kb deletion containing 19 genes including a fatty acyl-ACP thioesterase B gene (FATB1a). This deletion was associated with reduced palmitic acid content in seeds and was the molecular cause of a previously reported nonfunctional FATB1a allele, fap nc . The M23 and N0304-304-3 deletions were located in duplicated genome segments retained from the Glycine-specific whole genome duplication that occurred 13 million years ago. The homoeologous genes in these duplicated regions shared a strong similarity in both their encoded protein sequences and transcript accumulation levels, suggesting that they may have conserved and important functions in seeds. The functional conservation of homoeologous genes may result in genetic redundancy and gene dosage effects for their associated seed traits, explaining why the large deletion did not cause lethal effects or completely eliminate palmitic acid in N0304-303-3. PMID- 27179526 TI - A Social Reinforcement Learning Hypothesis of Mutual Reward Preferences in Rats. AB - Although the use of neuroimaging techniques has revealed much about the neural correlates of social decision making (SDM) in humans, it remains poorly understood how social stimuli are represented, and how social decisions are implemented at the neural level in humans and in other species. To address this issue, the establishment of novel animal paradigms allowing a broad spectrum of neurobiological causal manipulations and neurophysiological recordings provides an exciting tool to investigate the neural implementation of social valuation in the brain. Here, we discuss the potential of a rodent model, Rattus norvegicus, for the understanding of SDM and its neural underpinnings. Particularly, we consider recent data collected in a rodent prosocial choice task within a social reinforcement framework and discuss factors that could drive SDM in rodents. PMID- 27179527 TI - Development of a Japanese version of the BREAST-Q and the traditional psychometric test of the mastectomy module for the assessment of HRQOL and patient satisfaction following breast surgery. AB - BACKGROUND: An understanding of health-related quality of life (HRQOL) is of utmost importance in both oncological and esthetic breast surgery. The BREAST-Q is a patient-reported outcome (PRO) measure that investigates HRQOL and patient satisfaction before and after breast surgery. The aim of this study was to develop a Japanese version of the BREAST-Q including the mastectomy module, the reconstruction module, the augmentation module and the reduction/mastopexy module, and to assess the psychometric properties of the mastectomy module among Japanese women. METHODS: The Japanese version of the BREAST-Q was developed through forward translation, backward translation and patient testing. Traditional psychometric testing of the mastectomy module was administered to 45 post-mastectomy patients. RESULTS: The mastectomy, reconstruction, augmentation and reduction/mastopexy modules were formally developed into Japanese. Despite cultural difference between Japanese women and original target population, the contents were considered to be valid among Japanese woman. With the exception of the sexual well-being subscale, good reliability and validity were evident for the mastectomy module (Test-retest reliability 0.76-0.95, Chronbach's alpha coefficient 0.77-0.98). CONCLUSIONS: The BREAST-Q Japanese version is a useful PRO measure for investigating the impact of breast surgery on HRQOL and patient satisfaction. Further validation in younger Japanese women is needed to determine the usefulness of the sexual well-being subscale. PMID- 27179528 TI - Sequestration of Dimethylsulfoniopropionate (DMSP) and Acrylate from the Green Alga Ulva Spp. by the Sea Hare Aplysia juliana. AB - Many animals sequester secondary metabolites from their food. In this study, we hypothesized that the sea hare Aplysia juliana sequesters secondary metabolites from green algae. To test this, we performed NMR-based metabolomic analysis on methanol extracts of Ulva spp. and A. juliana. Another sea hare, Bursatella leachii, which mainly feeds on another type of alga, was added to this analysis as an outgroup. Two body parts of the sea hares, skin and digestive glands, were used in the analysis. Principal component analysis (PCA) on the NMR data of these samples detected biomarkers common to Ulva spp. and A. juliana. This result indicates sequestration of secondary metabolites by the herbivore from the plants. The biomarker metabolites were identified as dimethylsulfoniopropionate (DMSP) and acrylate, which were concentrated in skin of A. juliana and were released from the skin of live animals when physically stressed. Thus, our NMR based metabolomic study revealed sequestration of algae-derived secondary metabolites in skin of A. Juliana, and in the discharge of the metabolites under conditions that mimic attack by predators. PMID- 27179529 TI - Rhodococcus opacus B4: a promising bacterium for production of biofuels and biobased chemicals. AB - Bacterial lipids have relevant applications in the production of renewable fuels and biobased oleochemicals. The genus Rhodococcus is one of the most relevant lipid producers due to its capability to accumulate those compounds, mainly triacylglycerols (TAG), when cultivated on different defined substrates, namely sugars, organic acids and hydrocarbons but also on complex carbon sources present in industrial wastes. In this work, the production of storage lipids by Rhodococcus opacus B4 using glucose, acetate and hexadecane is reported for the first time and its productivity compared with Rhodococcus opacus PD630, the best TAG producer bacterium reported. Both strains accumulated mainly TAG from all carbon sources, being influenced by the carbon source itself and by the duration of the accumulation period. R. opacus B4 produced 0.09 and 0.14 g L(-1) at 24 and 72 h, with hexadecane as carbon source, which was 2 and 3.3 fold higher than the volumetric production obtained by R. opacus PD630. Both strains presented similar fatty acids (FA) profiles in intact cells while in TAG produced fraction, R. opacus B4 revealed a higher variability in fatty acid composition than R. opacus PD630, when both strains were cultivated on hexadecane. The obtained results open new perspectives for the use of R. opacus B4 to produce TAG, in particular using oily (alkane-contaminated) waste and wastewater as cheap raw-materials. Combining TAG production with hydrocarbons degradation is a promising strategy to achieve environmental remediation while producing added value compounds. PMID- 27179530 TI - Management of pediatric intracranial low-grade gliomas: long-term follow-up after radiation therapy. AB - INTRODUCTION: The treatment of pediatric intracranial low-grade gliomas (LGG) generally begins with maximal safe resection. Radiation therapy (RT) and chemotherapy are typically reserved for patients with incomplete resection and/or disease progression. We report long-term treatment outcomes and toxicities in a cohort of pediatric patients with LGG after RT. METHODS: Thirty-four patients <21 years old with intracranial LGG who were treated with RT at the Johns Hopkins Hospital were included in this retrospective analysis. Patients were evaluated for overall survival (OS), progression-free survival (PFS), recurrence patterns, and treatment toxicities using descriptive statistics, Kaplan-Meier curves, and Cox proportional hazard regressions. RESULTS: The mean age at diagnosis was 7.9 years (range 1.2-18.3 years) and mean age at RT was 9.8 years (range 3.0-28.9 years). The median follow-up time was 9.8 years after radiation (range 0.8-33.3 years). The estimated 10-year OS and PFS after RT were 92 and 74 %, respectively. Twelve patients had disease progression after RT, and all recurrences were local. Two patients died due to disease progression 2.3 and 9.1 years after RT. One patient had malignant transformation of LGG to high-grade glioma. No significant predictors of PFS were identified on uni- or multivariate analysis. Late effects of LGG and treatment seen were endocrine deficiencies in 16 patients, visual problems in 10 patients, hearing loss in 4 patients, special education requirements for 5 patients, and a vascular injury/demyelination secondary to RT in 1 patient. CONCLUSION: Our study suggests that the use of radiation in patients with intracranial LGG results in excellent OS and PFS with acceptable toxicity at long-term follow-up. PMID- 27179531 TI - Management of infectious intracranial aneurysms in the pediatric population. AB - INTRODUCTION: Infectious intracranial aneurysms (IIAs) account for approximately 15 % of all pediatric intracranial aneurysms. Histologically, they are pseudoaneurysms that develop in response to an inflammatory reaction within the adventitia and muscularis layers, ultimately resulting in disruption of both the internal elastic membrane and the intima. The majority of pediatric IIAs are located within the anterior circulation, and they can be multiple in 15-25 % of cases. BACKGROUND: The most common presentation for an IIA is intracerebral and/or subarachnoid hemorrhage. In children with a known diagnosis of infective endocarditis who develop new neurological manifestations, it is imperative to exclude the existence of an IIA. The natural history of untreated infectious aneurysms is ominous; they demonstrate a high incidence of spontaneous rupture. High clinical suspicion, prompt diagnosis, and adequate treatment are of paramount importance to prevent devastating neurological consequences. DISCUSSION: The prompt initiation of intravenous broad-spectrum antibiotics represents the mainstay of treatment. Three questions should guide the management of pediatric patients with IIAs: (a) aneurysm rupture status, (b) the presence of intraparenchymal hemorrhage or elevated intracranial pressure, and (c) relationship of the parent vessel to eloquent brain tissue. Those three questions should orient the treating physician into either antibiotic therapy alone or in combination with microsurgical or endovascular interventions. This review discusses important aspects of the epidemiology, the diagnosis, and the management of IIAs in the pediatric population. PMID- 27179532 TI - Epilepsy surgery in pediatric epileptic encephalopathy: when interictal EEG counts the most. AB - PURPOSE: Traditionally, seizure onset localization in ictal electro encephalography (EEG) is the main factor guiding resective epilepsy surgery. The situation is often different in infantile epileptic encephalopathy. We demonstrate the importance of the underrated interictal (rather than ictal) surface EEG in informing decision-making in epilepsy surgery for children with epileptic encephalopathy caused by subtle focal cortical dysplasia (FCD). METHODS: We present a small case series of three children who had an epileptic encephalopathy with either epileptic spasms or tonic seizures. All three were thought initially to have normal neuroimaging. RESULTS: Ictal EEG localizing features were seen in none and lateralizing features were seen only clinically in one of the three. However, the interictal EEG showed persistent and consistent focal irregular slowing in all, particularly after medically resolving the diffuse encephalopathy. Subtle FCDs were uncovered in all. Surgery was performed in all with excellent outcome. CONCLUSION: In infantile epileptic encephalopathy caused by subtle FCD, the often underrated interictal surface EEG (particularly persistent foal irregular slowing) informs the most; not only to the target area for surgical resection but also to its extent. This may negate the need for unnecessary and sometimes non-informative invasive monitoring in these cases. A matter of "zooming out" to define the extent of a resectable abnormality rather than "zooming in" to define a seemingly localized epileptic focus that may change with time. PMID- 27179533 TI - Factors associated with the timeliness of postnatal surgical repair of spina bifida. AB - PURPOSE: Clinical guidelines recommend repair of open spina bifida (SB) prenatally or within the first days of an infant's life. We examined maternal, infant, and health care system factors associated with time-to-repair among infants with postnatal repair. METHODS: This retrospective, statewide, population based study examined infants with SB born in Florida 1998-2007, ascertained by the Florida Birth Defects Registry. We used procedure codes from hospital discharge records to identify the first recorded myelomeningocele repair (ICD-9 CM procedure code 03.52) among infants with birth hospitalizations. Using Poisson multivariable regression, we examined time-to-repair by hydrocephalus, SB type (isolated [no other coded major birth defect] versus non-isolated), and other selected factors. RESULTS: Of 199 infants with a recorded birth hospitalization and coded myelomeningocele repair, 87.9 % had hydrocephalus and 19.6 % had non isolated SB. About 76.4 % of infants had repair by day 2 of life. In adjusted analyses, infants with hydrocephalus were more likely to have timely repair (adjusted prevalence ratio (aPR) = 1.48, 95 % confidence interval (CI) 1.02-2.14) than infants without hydrocephalus. SB type was not associated with repair timing. Infants born in lower level nursery care hospitals with were less likely to have timely repairs (aPR = 0.71, 95 % CI 0.52-0.98) than those born in higher level nursery care hospitals. CONCLUSIONS: Most infants with SB had surgical repair in the first 2 days of life. Lower level birth hospital nursery care was associated with later repairs. Prenatal diagnosis can facilitate planning for a birth hospital with higher level of nursery care, thus improving opportunities for timely repair. PMID- 27179535 TI - Painful pediatric traumatic neuroma: surgical management and clinical outcomes. AB - PURPOSE: Painful neuromas can limit function and decrease quality of life. Although management of traumatic neuromas in adults is well represented in the literature, traumatic neuromas are seen less frequently in children and adolescents, and their management is underrepresented in the literature. We present a sample of our clinical experience with painful pediatric neuromas and describe the surgical management and clinical outcomes of these cases. METHODS: A retrospective case review was conducted on patients treated at our pediatric tertiary care center. The same surgeon was responsible for management and follow up of all patients. RESULTS: The sample of five patients was 60 % female and had a mean age of 12.2 (3-16) years. Each case was managed using a different surgical technique. All the patients had acceptable outcomes with a mean post-operative pain score of 0.4 (0-2) out of 10 and no residual functional outcomes. CONCLUSIONS: It is important for clinicians to recognize that pediatric patients develop painful neuromas following nerve trauma and to understand the neurophysiologic basis for their management. Our report demonstrates that many of the techniques that we use for neuroma repair in adults are applicable in the pediatric population. PMID- 27179534 TI - Glial heterotopia of the orbit: a rare cause of proptosis. AB - BACKGROUND: Glial heterotopia is defined as presence of normal glial tissue in an unusual location without connection with the brain. It is a very rare clinical entity occuring mostly in the head and neck region which is generally present at birth. Orbital location is very rare. CASE REPORT: We report a case of a 4-month old girl presenting congenital proptosis with progressive increase. CT scan revealed an intraorbital mass without bony defect. The patient was operated, and resection was subtotal. Histologically, the tumor was composed of glial tissue with plexus choroid and pathologist concluded glial heterotopia. The child is under constant medical supervision because recurrences can be observed after incomplete resection; she had no new clinical signs at 18 months follow-up. PMID- 27179536 TI - The current role of diagnostic imaging in the preoperative workup for refractory neonatal brachial plexus palsy. AB - INTRODUCTION: Despite recent improvements in perinatal care, the incidence of neonatal brachial plexus palsy (NBPP) remains relatively common. CT myelography is currently considered to be the optimal imaging modality for evaluating nerve root integrity. Recent improvements in MRI techniques have made it an attractive alternative to evaluate nerve root avulsions (preganglionic injuries). AIM: We demonstrate the utility of MRI for the evaluation of normal and avulsed spinal nerve roots. We also show the utility of ultrasound in providing useful preoperative evaluation of the postganglionic brachial plexus in patients with NBPP. PMID- 27179537 TI - Rhizophagus intraradices or its associated bacteria affect gene expression of key enzymes involved in the rosmarinic acid biosynthetic pathway of basil. AB - In recent years, arbuscular mycorrhizal fungi (AMF) have been reported to enhance plant biosynthesis of secondary metabolites with health-promoting activities, such as polyphenols, carotenoids, vitamins, anthocyanins, flavonoids and lycopene. In addition, plant growth-promoting (PGP) bacteria were shown to modulate the concentration of nutraceutical compounds in different plant species. This study investigated for the first time whether genes encoding key enzymes of the biochemical pathways leading to the production of rosmarinic acid (RA), a bioactive compound showing antioxidant, antibacterial, antiviral and anti inflammatory properties, were differentially expressed in Ocimum basilicum (sweet basil) inoculated with AMF or selected PGP bacteria, by using quantitative real time reverse transcription PCR. O. basilicum plants were inoculated with either the AMF species Rhizophagus intraradices or a combination of two PGP bacteria isolated from its sporosphere, Sinorhizobium meliloti TSA41 and Streptomyces sp. W43N. Present data show that the selected PGP bacteria were able to trigger the overexpression of tyrosine amino-transferase (TAT), hydroxyphenylpyruvate reductase (HPPR) and p-coumaroyl shikimate 3'-hydroxylase isoform 1 (CS3'H iso1) genes, 5.7-fold, 2-fold and 2.4-fold, respectively, in O. basilicum leaves. By contrast, inoculation with R. intraradices triggered TAT upregulation and HPPR and CS3'H iso1 downregulation. Our data suggest that inoculation with the two selected strains of PGP bacteria utilised here could represent a suitable biotechnological tool to be implemented for the production of O. basilicum plants with increased levels of key enzymes for the biosynthesis of RA, a compound showing important functional properties as related to human health. PMID- 27179539 TI - Genetic admixture and lineage separation in a southern Andean plant. AB - Mountain uplifts have generated new ecologic opportunities for plants, and triggered evolutionary processes, favouring an increase on the speciation rate in all continents. Moreover, mountain ranges may act as corridors or barriers for plant lineages and populations. In South America a high rate of diversification has been linked to Andean orogeny during Pliocene/Miocene. More recently, Pleistocene glacial cycles have also shaped species distribution and demography. The endemic genus Escallonia is known to have diversified in the Andes. Species with similar morphology obscure species delimitation and plants with intermediate characters occur naturally. The aim of this study is to characterize genetic variation and structure of two widespread species of Escallonia: E. alpina and E. rubra We analyzed the genetic variation of populations of the entire distribution range of the species and we also included those with intermediate morphological characters; a total of 94 accessions from 14 populations were used for the Amplified Fragment Length Polymorphism (AFLP) analysis. Plastid DNA sequences (trnS-trnG, 3'trnV-ndhC intergenic spacers and the ndhF gene) from sixteen accessions of Escallonia species were used to construct a Statistical Parsimony network. Additionally, we performed a geometric morphometrics analysis on 88 leaves from 35 individuals of the two E. alpina varieties to further study their differences. Wright's Fst and analysis of molecular variance tests performed on AFLP data showed a significant level of genetic structure at the species and population levels. Intermediate morphology populations showed a mixed genetic contribution from E. alpina var. alpina and E. rubra both in the Principal Coordinates Analysis (PCoA) and STRUCTURE. On the other hand, E. rubra and the two varieties of E. alpina are well differentiated and assigned to different genetic clusters. Moreover, the Statistical Parsimony network showed a high degree of divergence between the varieties of E. alpina: var. alpina is more closely related to E. rubra and other species than to its own counterpart E. alpina var. carmelitana Geometric morphometrics analysis (Elliptic Fourier descriptors) revealed significant differences in leaf shape between varieties. We found that diversity in Escallonia species analyzed here is geographically structured and deep divergence between varieties of E. alpina could be associated to ancient evolutionary events like orogeny. Admixture in southern populations could be the result of hybridization at the margins of the parental species' distribution range. PMID- 27179538 TI - Capturing Parenting as a Multidimensional and Dynamic Construct with a Person Oriented Approach. AB - Although parenting is one of the most commonly studied predictors of child problem behavior, few studies have examined parenting as a multidimensional and dynamic construct. This study investigated different patterns of developmental trajectories of two parenting dimensions (harsh discipline [HD] and parental warmth [PW]) with a person-oriented approach and examined the associations between different parenting patterns and child externalizing problems and callous unemotional traits. Data were drawn from the combined high-risk control and normative sample (n = 753) of the Fast Track Project. Parent-reported HD and observer-reported PW from kindergarten to grade 2 were fit to growth mixture models. Two subgroups were identified for HD (low decreasing, 83.0 %; high stable, 17.0 %) and PW (high increasing, 78.7 %; low increasing, 21.3 %). The majority of parents (67.0 %) demonstrated the low decreasing HD and high increasing PW pattern, while the prevalence of the high stable HD and low increasing PW pattern was the lowest (6.8 %). Parenting satisfaction, parental depression, family socioeconomic status, and neighborhood safety predicted group memberships jointly defined by the two dimensions. Children from the high stable HD and low increasing PW pattern showed the highest levels of externalizing problems in grades 4 and 5. Children from the low decreasing HD and low increasing PW pattern showed the highest levels of callous-unemotional traits in grade 7. These findings demonstrate the utility and significance of a person oriented approach to measuring parenting as a multidimensional and dynamic construct and reveal the interplay between HD and PW in terms of their influences on child developmental outcomes. PMID- 27179540 TI - Spatiotemporal strategies that facilitate recruitment in a habitat specialist tree species. AB - Our understanding of processes underlying plant recruitment emerges from species and habitats that are widely distributed at regional and global scales. However, the applicability of dispersal-recruitment models and the role of dispersal limitation versus microsite limitation have not been examined for specialized habitats. In patchy, freshwater Myristica swamp forests (Western Ghats, India), we examine the roles of primary seed dispersal, secondary seed removal and microsite suitability for the establishment of a swamp specialist tree, Myristica fatua We estimated primary seed shadows, performed secondary removal experiments and enumerated recruits in swamp sites. Steady-state fruiting was observed with the extended production (>7 months) of small numbers of fruits. Frugivores dropped most of the large and heavy seeds under parent crowns, while a few seeds were transported over short distances by hornbills. Seed placement experiments indicated that removal, germination and establishment were similar within swamp microsites, while seeds failed to survive in matrix habitats surrounding the swamp. Crabs, which were major secondary removers of M. fatua, did not alter the initial seed dispersal patterns substantially, which led to the retention of seeds within the swamp. Distribution of saplings and adults from previous seasons also suggest that dispersal-recruitment dynamics in the swamp specialist M. fatua did not strictly follow predictions of Janzen-Connell model while abiotic effects were significant. Large seeds, steady-state fruiting and small crop sizes may be significant selective forces facilitating escape from density and distance dependent effects in space and time in specialist plant species such as M. fatua. PMID- 27179541 TI - Seed germination of seven desert plants and implications for vegetation restoration. AB - Germination cues reflect the conditions under which a species is likely to succeed in recruitment. Therefore, knowledge of the seed germination characteristics of key plant species in desertified areas is essential for restoration. The aims of this study were to evaluate the seed germination responses of seven native species, and to explore the implications for vegetation restoration. Seeds of seven desert species were sown in Petri dishes and subjected to various temperature and light conditions. The seeds germinated well at day/night temperatures of 25/15 degrees C and 30/20 degrees C but poorly at 35/25 degrees C. Seeds germinated best in the dark, and final germination percentages of all species were strongly inhibited at a photon irradiance of 1000 umol m(-2) s(-1) Based on these results and the environmental conditions of their natural habitat, Agropyron cristatum and Artemisia halodendron are best adapted to shifting sand dunes: Elymus dahuricus, Caragana korshinskii and C. microphylla for semi-fixed sand dunes: and Medicago sativa and Melilotus suaveolen for fixed sand dunes. If seeds are sown in early May, they will likely be buried in sand, and the precipitation and temperature conditions will be suitable for seedling survival. PMID- 27179542 TI - Acute abdomen resulting in cholecystectomy in a healthy young woman. PMID- 27179543 TI - Investigation of low back and shoulder demand during cardiopulmonary resuscitation. AB - Limited research has examined the effect of different compression-ventilation ratios on the ergonomic demand of performing cardiopulmonary resuscitation (CPR) over time. This study aimed to compare the biomechanical demand of performing continuous chest compression CPR (CCC-CPR) and standard CPR (30:2 compression to breath ratio). Fifteen CPR certified individuals performed both standard CPR and CCC-CPR, randomly assigned, for three 2-min periods. Trunk and upper limb muscle activation, lumbar spine posture and compression force applied to a testing mannequin chest were measured throughout each CPR trial. No differences in muscle activation of spine posture were observed, however chest compression force decreased over the two minutes (p < 0.0001). Further, this drop in force was larger and initiated immediately during the CCC-CPR trials. This immediate drop in force during the CCC-CPR trials may be an anticipatory adjustment in order to be able to sustain continuous compressions for the full 2 min duration. PMID- 27179544 TI - Long-term Risk of Heart Failure and Myocardial Dysfunction After Thoracic Radiotherapy: A Systematic Review. AB - BACKGROUND: Chest irradiation is a commonly used treatment for malignancy, with demonstrated symptomatic and survival benefit. The frequency and presentation of cardiovascular complications of radiotherapy remains unclear. METHODS: We performed a systematic review to evaluate the prevalence and manifestations of myocardial dysfunction (asymptomatic and symptomatic) in long-term cancer survivors treated with radiotherapy. RESULTS: Thoracic radiotherapy is associated with increased risk of heart failure in long-term follow-up, with hazard ratios ranging from 2.7 to 7.4 for Hodgkin lymphoma, and 1.5-2.4 for breast cancer. Although ejection fraction is often normal, systolic dysfunction has been more widely reported with modern techniques including 2-dimensional speckle strain and cardiac magnetic resonance. This might have implications for the selection of patients for cardioprotection. Despite common emphasis, diastolic functional abnormalities were infrequent in the long term. A limited amount of data suggest that right ventricular dysfunction is important in this population. CONCLUSIONS: The reports were heterogeneous, used different treatments, end points, and definitions of myocardial dysfunction, and most studies on the cardiac consequences of radiotherapy involved small numbers of patients and were published decades ago, making it difficult to formulate definitive conclusions for the current era. PMID- 27179545 TI - Cardiac Outcomes in Survivors of Pediatric and Adult Cancers. AB - More than 80% of children and 60% of adults with cancer will become long-term survivors, emphasizing the importance of late effects of cancer therapy. Cardiotoxicity due to chemotherapy and radiation is a frequent cause of serious morbidity and premature mortality in survivors. Anthracyclines, a core component of many treatment regimens, have been implicated as a principal cause of irreversible cardiomyopathy. Approximately 60% of anthracycline-treated children will develop echocardiographic evidence of cardiac dysfunction, and 10% of those treated with high-dose anthracyclines will develop congestive heart failure within the 20 years after therapy. Adults treated with trastuzumab are at risk of a cardiomyopathy that is usually reversible. As many as 12% of adults treated with trastuzumab and 20% of those who have also received an anthracycline will develop cardiotoxicity within 5 years. Risk factors for cardiomyopathy include patient (eg, age, sex, genetic predisposition) and treatment characteristics (eg, cumulative anthracycline dose). Radiotherapy to a field involving the heart increases the risk of cardiomyopathy, coronary artery disease, valvular dysfunction, arrhythmias, and pericardial disease. Surveillance guidelines are available to guide long-term cardiac follow-up of childhood cancer survivors, but not for survivors of adult cancers; however, periodic follow-up to detect cardiac dysfunction may be reasonable. Modifiable cardiac risk factors such as hypertension, smoking, and dyslipidemia interact with cancer therapies to increase the risk of cardiac disease, emphasizing the importance of risk-factor control. Coordination of care between oncologists and cardiologists would optimize care for those individuals at high risk of cardiotoxicity who would benefit from appropriate surveillance and treatment strategies. PMID- 27179546 TI - Long-term Complications After Transcatheter Atrial Septal Defect Closure: A Review of the Medical Literature. AB - Percutaneous closure has evolved to become the first-line treatment strategy for most cases of secundum atrial septal defect (ASD) in both adults and children. Its safety and efficacy have been proved; percutaneous ASD occlusion offers many advantages over surgical closure, including avoidance of cardiopulmonary bypass, avoidance of sternotomy scar, shorter hospitalization, and a potentially lower incidence of postprocedural complications. Periprocedural course and short-term outcome have been widely described, with low mortality and morbidity rates. However, the wide use of ASD closure devices and the growing experience worldwide brought some delayed and rare complications to light. Device thrombosis and cardiac erosion are the most severe late complications of device closure, whereas atrial arrhythmias are the most common. Other delayed complications include nickel allergy, cardiac conduction abnormalities, valvular damage, and device endocarditis. The long-term complication rate is not null and, although rare, some of these complications may be sudden and potentially life-threatening. Moreover, the occurrence and rate of these complications vary with the different devices used currently or in the past. Therefore, both operators and patients need to be aware of these issues to assist them in the choice of intervention or device, or both, and to adapt follow-up modalities. In this review, we sought to describe the type, incidence, and outcome of these rare but potentially serious device closure delayed complications. PMID- 27179547 TI - Identification of Two Novel LAMP2 Gene Mutations in Danon Disease. AB - BACKGROUND: Danon disease is a rare X-linked inherited disorder characterized by massive left ventricular hypertrophy, skeletal muscle dystrophy, and mental retardation. The disease is caused by mutations in the LAMP2 gene encoding for lysosome-associated membrane protein-2. METHODS: Two young male patients with hypertrophic cardiomyopathy, characterized by marked, concentric left ventricular hypertrophy, elevated levels of creatine kinase, and manifest limb-girdle muscular dystrophy in 1 case, were investigated. Genetic screening included direct sequencing of the whole coding sequence of the LAMP2 gene. RESULTS: Genetic analysis identified 2 novel LAMP2 gene mutations. In Family A, a G-A transition (c.962G > A) leading to a nonsense mutation at codon 321 (p.Trp321Ter), and in Family B, a one-nucleotide insertion (c.973insC) leading to a full frame-shift (p.Pro324+24X) was detected in exon 8 of the LAMP2 gene. Family screening identified 8 mutation carriers, with 4 nonpenetrant cases and 3 additional, probably affected family members without DNA diagnosis. The cardiac phenotype was hypertrophic cardiomyopathy in all cases, including female mutation carriers. Five disease-related deaths occurred in the families, at an average age of 33 +/- 16 years, which was clearly lower in male than in female patients (28 +/- 7 vs 42 +/- 25 years). A high prevalence of arrhythmias or conduction abnormalities was also observed. CONCLUSIONS: The reported 2 novel LAMP2 gene mutation carrier families, one of them being one of the largest reported to date, highlight the malignant clinical course of Danon disease, characterized by a high rate of disease-related death at an early age and a high prevalence of arrhythmias or conduction abnormalities. PMID- 27179548 TI - "Tertiary Precision Prevention" for Concussion: Customizing Care by Predicting Outcomes. PMID- 27179549 TI - Gastrostomy Tube Complications. PMID- 27179550 TI - Asymmetric Hypertrophic Pyloric Stenosis with Concurrent Pancreatic Rest Presenting as Gastric Outlet Obstruction. PMID- 27179551 TI - An Unusual Intussusception. PMID- 27179552 TI - Applied Behavior Analysis as Treatment for Autism Spectrum Disorder. PMID- 27179553 TI - Different procedures of diphenyleneiodonium chloride addition affect neutrophil extracellular trap formation. AB - A unique strategy, in which invading microorganisms are being caught in web-like structures composed mainly of DNA, involves a recently described phenomenon called NETosis. This process seems to be related to the production of reactive oxygen species (ROS). In our study, the influence of diphenyleneiodonium chloride (DPI), which diminishes ROS production, was assessed in the context of neutrophil extracellular trap (NET) release. According to protocol, two distinguished procedures were compared, the first one involving DPI elimination from sample before cell activation and the second one proceeding without the step of inhibitor washout. The kinetics of DNA release was monitored by fluorometric assay, and NET formation was observed by fluorescent microscopy. The addition of DPI to the sample led to a reduction of extracellular DNA release. The strongest inhibition was noticed after treatment with 10 MUM DPI, which was removed from medium before stimulation with phorbol-12-myristate-13-acetate (PMA). Our findings confirmed that DPI is able to block NET creation. However, the addition of DPI together with PMA or the addition of inhibitor initially and then washing it out before stimulation resulted in different levels of NET formation. Finally, DPI that remained in the system induced specific morphological changes in the neutrophils' nuclei that was not observed in the DPI washed out from sample. PMID- 27179554 TI - The soluble epoxide hydrolase determines cholesterol homeostasis by regulating AMPK and SREBP activity. AB - Inhibition or deletion of the soluble epoxide hydrolase (sEH) has been linked to reduced cholesterol and protection against atherosclerosis. This study set out to identify sEH substrate(s) or product(s), altered in livers from sEH(-/-) mice that contribute to these beneficial effects. In livers and isolated hepatocytes, deletion of sEH decreased expression of HMG CoA reductase, fatty acid synthase and low density lipoprotein receptor. Sterol regulatory element binding proteins (SREBPs) regulate the expression of all three enzymes and SREBP activation was attenuated in the absence of sEH. The effect was attributed to the AMPK-activated protein kinase (AMPK) which was activated in the absence of sEH. Livers from wild type versus sEH(-/-) littermates contained significantly higher levels of the sEH substrate 12,13-epoxyoctadecenoic acid, which elicited AMPK activation, while the corresponding sEH product was inactive. Thus, AMPK activation and subsequent inhibition of SREBP can account for the altered expression of lipid metabolizing enzymes in sEH(-/-) mice. PMID- 27179556 TI - Surgical treatment of osteonecrosis of the jaw with the use of platelet-rich fibrin: a prospective study of 15 patients. AB - The objective of this study was to evaluate the outcome of the surgical treatment of osteonecrosis of the jaw (ONJ) with the additional use of autologous membranes of platelet-rich fibrin (PRF). The study population consisted of 15 patients with ONJ lesions in the maxilla (n=3), mandible (n=11), or both (n=1). Eight patients had malignant disease and were treated with high-dose anti-resorptive medication; seven were treated with low-dose anti-resorptive drugs for osteoporosis. Thirteen patients had grade 2 ONJ lesions and two had grade 3 lesions. The following standardized surgical technique was applied: resection of necrotic bone, mobilization of mucoperiosteal flaps, and multiple layer coverage of bone with PRF membranes. At follow-up 7-20 months after surgery, complete mucosal healing and an absence of symptoms were found in 14 of the 15 patients (93%). The patient with persistent bone exposure had a grade 3 ONJ lesion before surgery. This study suggests that the use of PRF membranes in the surgical treatment of grade 2 ONJ may be a contributing factor to a successful outcome. PMID- 27179557 TI - An Individualized Approach to Treatment-Resistant Bipolar Disorder: A Case Series. AB - CONTEXT: Treatment-resistant bipolar disorder (TRBD) is an increasingly prevalent, debilitating condition with substandard treatment outcomes. Polypharmacy has become the mainstay among practitioners though long-term efficacy of this method has not been adequately tested. OBJECTIVE: Determine retrospectively if individualized, integrative treatment strategies applied while withdrawing pharmaceuticals were beneficial and safe among a TRBD clinic population. DESIGN: A chart review was performed for six adult patients, treated in a private psychiatric practice. Data were collected regarding psychiatric diagnosis, hospitalizations, medications, side effects, substance abuse, and applied treatments. RESULTS: Using individualized, integrative psychiatric treatment methods, the majority of medications were eliminated. Long-term remission was attained in all cases, defined as clinical stability with no discernable symptoms of bipolar disorder for at least one year. CONCLUSIONS: Applying an integrative treatment approach, and eliminating most medications, provided lasting resolution of symptoms and side effects in a selected sample of TRBD outpatients. These data may provide the basis for future randomized, controlled trials. PMID- 27179555 TI - Oxidized HDL is a potent inducer of adipogenesis and causes activation of the Ang II and 20-HETE systems in human obese females. AB - BACKGROUND: Oxidized-HDL (OX-HDL) has been reported to increase coronary events in obese patients; however, OX-HDL has not been studied in subjects with the metabolic syndrome. A high body mass index (BMI) correlates positively with higher levels of metabolic syndrome biomarkers including vasoconstrictors and adipokines. We hypothesize that a subject with a high BMI would present with higher levels of OX-HDL, 20-HETE and Angiotensin II (Ang II) with a reciprocal reduction in serum adiponectin. METHODS: Female subjects with a BMI of 17-25 and a BMI of 30-40, without overt cardiovascular disease, were enrolled in the study. All patients had a history and physical exam documenting the absence of signs and symptoms of cardiovascular disease. Appropriate screening was done and documented. Blood pressure was taken at two discrete points. The BP data are presented as the average. Changes in the relationship between BMI, OX-HDL, 20 HETE, Ang II, TNFalpha, isoprostane and adiponectin were examined. In addition, the effects of OX-HDL, 20-HETE and Ang II on adipogenesis were examined in human MSC derived adipocytes. RESULTS: Subjects with a high BMI>30 displayed an increase in OX-HDL and isoprostane (P<0.05) compared to those with the lower BMI<25 which was associated with an increase in Ang II and 20-HETE (p<0.05). Serum TNFalpha levels increased in subjects with a high BMI, compared to subjects with the lower BMI (p<0.05). In contrast, adiponectin levels were increased in subjects with a low BMI compared to obese subjects (p<0.05). In MSC derived adipocytes OX-HDL increased adipogenesis 6 fold at a concentration of 50ng compared to untreated adipocytes. Adipocytes treated with Ang II and 20-HETE also displayed increased adipogenesis (p<0.05), which was attenuated by endogenous increases of the anti-oxidant heme oxygenase-1. Our study demonstrates that OX HDL presents a unique inflammatory biomarker profile in obese females with the metabolic syndrome at risk for developing cardiovascular disease. CONCLUSIONS: Females with increased BMI (30-40) exhibit a marked increase in OX-HDL and isoprostane levels, which was associated with an increase in 20-HETE, TNF alpha and Ang II and decreased levels of adiponectin when compared to a group with a low BMI. OX-HDL had a more powerful adipogenic effect when compared to 20-HETE and Ang II. Our study demonstrates that OX-HDL presents a unique inflammatory biomarker profile in obese females with the metabolic syndrome at risk for developing cardiovascular disease. This represents a novel mechanism by which females with a high BMI and controlled blood pressure remain "at risk" for the development of the metabolic syndrome as a result of increased adipogenesis by OX HDL and activation of the 20-HETE and Ang II systems. PMID- 27179558 TI - Efficient visual information for unfamiliar face matching despite viewpoint variations: It's not in the eyes! AB - Faces are encountered in highly diverse angles in real-world settings. Despite this considerable diversity, most individuals are able to easily recognize familiar faces. The vast majority of studies in the field of face recognition have nonetheless focused almost exclusively on frontal views of faces. Indeed, a number of authors have investigated the diagnostic facial features for the recognition of frontal views of faces previously encoded in this same view. However, the nature of the information useful for identity matching when the encoded face and test face differ in viewing angle remains mostly unexplored. The present study addresses this issue using individual differences and bubbles, a method that pinpoints the facial features effectively used in a visual categorization task. Our results indicate that the use of features located in the center of the face, the lower left portion of the nose area and the center of the mouth, are significantly associated with individual efficiency to generalize a face's identity across different viewpoints. However, as faces become more familiar, the reliance on this area decreases, while the diagnosticity of the eye region increases. This suggests that a certain distinction can be made between the visual mechanisms subtending viewpoint invariance and face recognition in the case of unfamiliar face identification. Our results further support the idea that the eye area may only come into play when the face stimulus is particularly familiar to the observer. PMID- 27179559 TI - Significance of microRNA 21 in gastric cancer. AB - Despite promising developments of treatment, the mortality due to gastric cancer remains high and the mechanisms of gastric cancer initiation and the development also remains elusive. It has been reported that patients with positive serologic tests for H. pylori have a higher risk of the development of gastric cancer. microRNAs (miRNAs) are short non-coding RNA molecules consisting of 21-25 nucleotides (nt) in length. The miRNAs silence their cognate target genes by inhibiting mRNA translation or degrading the mRNA molecules by binding to their 3'-untranslated (UTR) regions and plays a very important role in cancer biology. Recent evidences indicate that miR-21 is overexpressed in tumour tissue, including gastric cancer and plays a vital role in tumour cell proliferation, apoptosis, invasion and angiogenesis. Elevated levels of miR-21 is associated with downregulation of tumour suppressor genes, such as programmed cell death 4 (PDCD4), tissue inhibitor of metalloproteinase 3, phosphatase and tensin homolog (PTEN), tropomyosin 1, ras homolog gene family member B, and maspin. Silencing of miR-21 through the use of a miR-21 inhibitor affected cancer cell viability, induced cell cycle arrest and increased chemosensitivity to anticancer agents indicating that miR-21 functions as an oncogene. Although an increased expression level of miR-21 has been observed in gastric cancer, studies related to the role of miR-21 in gastric cancer progression is very limited. The main thrust of this mini review is to explain the potency of miR-21 as a prognostic and/or diagnostic biomarker and as a new target for clinical therapeutic for interventions of gastric cancer progression. PMID- 27179560 TI - PC-FACS. AB - PC-FACS(FastArticleCriticalSummaries for Clinicians inPalliativeCare) provides hospice and palliative care clinicians with concise summaries of the most important findings from more than 100 medical and scientific journals. If you have colleagues who would benefit from receiving PC-FACS, please encourage them to join the AAHPM at aahpm.org. Comments from readers are welcomed at pc facs@aahpm.org. PMID- 27179562 TI - A single electrochemical biosensor for detecting the activity and inhibition of both protein kinase and alkaline phosphatase based on phosphate ions induced deposition of redox precipitates. AB - Protein kinase (PKA) and alkaline phosphatase (ALP) are clinically relevant enzymes for a number of diseases. In this work, we developed a new simple electrochemical biosensor for the detection of the activity and inhibition of both PKA and ALP. One common feature of the PKA and ALP catalyzing process is that PKA can hydrolysis adenosine-5'-triphosphate (ATP) and ALP can hydrolysis pyrophosphate, both reactions produce phosphate ions, and the amount of phosphate ion produced is proportional to enzyme activity. Our assay is based on the principle that phosphate ions react with molybdate to form redox molybdophosphate precipitates on the electrode surface, thus generating electrochemical current. The detection limit for PKA and ALP were much lower than existing assays. The biosensor has good specificity and was used to measure drug-stimulated PKA from lysates of HeLa cells. We also evaluated the use of the biosensor as a screening tool for enzyme inhibitors. To the best of our knowledge, this is the first report of a biosensor capable of detecting the activity of both PKA and ALP. This tool has the potential to simplify PKA and ALP clinical measurement, thereby improving diagnostics of relevant diseases. It also may serve as the basis for a simple screening method for new enzyme inhibitors for disease treatment. PMID- 27179561 TI - Selective and sensitive detection of MiRNA-21 based on gold-nanorod functionalized polydiacetylene microtube waveguide. AB - Development of rapid, highly selective and sensitive miRNA detection in a complex biological environment has attracted considerable attention. Herein, we describe a novel two step method to construct gold-nanorod functionalized polydiacetylene (PDA) microtube for miRNA detection. In PDA microtube, with a one-dimensional (1D) waveguide nature, the excitation position and emission out-coupling position are far apart, thus helpful in reducing contribution of auto-fluorescence from biological sample. The use of specially designed toehold-mediated strand displacement reaction enables the reliable and selective discrimination of miRNA sequences with high sequence homology. Based on the condensing enrichment effect, the detection limit of the proposed PDA microtube system is as low as 0.01nM, and it can be applied directly to detect disease-specific miRNA targets in human serum. This PDA microtube waveguide system can be further integrated into the chip for the potential applications in minimally invasive, portable clinical diagnostic equipment. PMID- 27179563 TI - Use of 3,3',5,5' tetramethylbenzidine as new electrochemical indicator of DNA hybridization and its application in genossensor. AB - Electrochemical tools are important biosensor platforms for disease diagnosis, due to their speediness, easiness, low cost and portability. However, for DNA detection, the use of indicators and/or intercalators is necessary to improve electrochemical sensitivity. Currently, ethidium bromide (EthBr) is the cheapest and most used DNA intercalators, but presents carcinogenic and teratogenic properties. Other indicators may be important for DNA photonic detection, and besides being more expensive, they behave similarly to EthBr. This investigation shows for the first time the use of tetramethylbenzidine(TMB) as a new remarkable non-carcinogenic DNA indicator for genosensing purposes, which may be used for nucleic acid detection of microorganisms, based on complementarity of base pairing between probe and target molecules. The results indicate that TMB can be used as a new electrochemical indicator readily applicable in genosensors, which is able to detect the hybridization of single stranded DNA probe with its complementary target strand. An additional advantage of TMB, beside its non genotoxicity, is the electrochemical reduction property, which prevents interference of serum components and other oxidative samples in the electrochemical analysis. PMID- 27179564 TI - Disposable self-support paper-based multi-anode microbial fuel cell (PMMFC) integrated with power management system (PMS) as the real time "shock" biosensor for wastewater. AB - A paper-based multi-anode microbial fuel cell (PMMFC) integrated with power management system (PMS) was developed as a disposable self-support real-time "shock" biosensor for wastewater. PMMFCs were examined at three types of shocks (chromium, hypochlorite and acetate) in a batch-mode chamber, and exhibited various responses to shock types and concentrations. The power output of PMMFC sensor was four times as the carbon cloth (CC)-based MFCs, indicating the advantage of paper-based anode for bacterial adhesion. The power output was more sensitive than the voltage output under shocks, and thus preventing the false signals. The simulation of power harvest using PMS indicated that PMMFC could accomplish more frequent data transmission than single-anode MFCs (PSMFC) and CC anode MFCs (CCMMFC), making the self-support wastewater monitor and data transmission possible. Compared with traditional MFC sensors, PMMFCs integrated with PMS exhibit the distinct advantages of tight paper-packed structure, short acclimation period, high power output, and high sensitivity to a wide range of shocks, posing a great potential as "disposable self-support shock sensor" for real time in situ monitoring of wastewater quality. PMID- 27179565 TI - Tunneling of redox enzymes to design nano-probes for monitoring NAD(+) dependent bio-catalytic activity. AB - Monitoring of bio-catalytic events by using nano-probes is of immense interest due to unique optical properties of metal nanoparticles. In the present study, tunneling of enzyme activity was achieved using redox cofactors namely oxidized cytochrome-c (Cyt-c) and Co-enzyme-Q (Co-Q) immobilized on Quantum dots (QDs) which acted as a bio-probe for NAD(+) dependent dehydrogenase catalyzed reaction. We studied how electron transfer from substrate to non-native electron acceptors can differentially modify photoluminescence properties of CdTe QDs. Two probes were designed, QD-Ox-Cyt-c and QD-Ox-Co-Q, which were found to quench the fluorescence of QDs. However, formaldehyde dehydrogenase (FDH) catalyzed reduction of Cyt-c and Co-Q on the surface of QDs lead to fluorescence turn-on of CdTe QDs. This phenomenon was successfully used for the detection of HCHO in the range of 0.01-100,000ng/mL (LOD of 0.01ng/mL) using both QD-Ox-Cyt-c (R(2)=0.93) and QD-Ox-Co-Q (R(2)=0.96). Further probe performance and stability in samples like milk, wine and fruit juice matrix were studied and we could detect HCHO in range of 0.001-100,000ng/mL (LOD of 0.001ng/mL) with good stability and sensitivity of probe in real samples (R(2)=0.97). Appreciable recovery and detection sensitivity in the presence of metal ions suggests that the developed nano-probes can be used successfully for monitoring dehydrogenase based bio catalytic events even in the absence of NAD(+). Proposed method is advantageous over classical methods as clean up/ derivatization of samples is not required for formaldehyde detection. PMID- 27179566 TI - Microfluidic-integrated DNA nanobiosensors. AB - Over the last few decades, an increased demand has emerged for integrating biosensors with microfluidic- and nanofluidic-based lab-on-chip (LOC) devices for point-of-care (POC) diagnostics, in the medical industry and environmental monitoring of pathogenic threat agents. Such a merger of microfluidics with biosensing technologies allows for the precise control of volumes, as low as one nanolitre and the integration of various types of bioassays on a single miniaturized platform. This integration offers several favorable advantages, such as low reagent consumption, automation of sample preparation, reduction in processing time, low cost analysis, minimal handling of hazardous materials, high detection accuracy, portability and disposability. This review provides a synopsis of the most recent developments in the microfluidic-integrated biosensing field by delineating the fundamental theory of microfluidics, fabrication techniques and a detailed account of the various transduction methods that are employed. Lastly, the review discusses state-of-the-art DNA biosensors with a focus on optical DNA biosensors. PMID- 27179568 TI - Hepatitis B plasmonic biosensor for the analysis of clinical serum samples. AB - A plasmonic biosensor for rapid detection of protein biomarkers in complex media is reported. Clinical serum samples were analyzed by using a novel biointerface architecture based on poly[(N-(2-hydroxypropyl) methacrylamide)-co (carboxybetaine methacrylamide)] brushes functionalized with bioreceptors. This biointerface provided an excellent resistance to fouling even after the functionalization and allowed for the first time the direct detection of antibodies against hepatitis B surface antigen (anti-HBs) in clinical serum samples using surface plasmon resonance (SPR). The fabricated SPR biosensor allowed discrimination of anti-HBs positive and negative clinical samples in 10min. Results are validated by enzyme-linked immunoassays of the sera in a certified laboratory. The sensor could be regenerated by simple treatment with glycine buffer. PMID- 27179567 TI - Novel electrochemical sensing platform for quantitative monitoring of Hg(II) on DNA-assembled graphene oxide with target recycling. AB - This work designs a new electrochemical sensing platform for the quantitative monitoring of mercury ion (Hg(2+)) on poly-T(15) oligonucleotide-functionalized graphene oxide by coupling with DNase I-assisted target recycling amplification. The assay was carried out on the basis of T-Hg(2+)-T coordination chemistry by using target-induced dissociation of indicator-labeled poly-T(15) oligonucleotide from graphene oxide nanosheets. The electronic signal was amplified through DNase I-triggered target recycling. Experimental results indicated that the amperometric response of DNA-based sensing platform deceased with the increasing Hg(2+) concentration in the sample, and has a detection limit of 0.12nM with a dynamic working range of up to 50nM. Our strategy afforded exquisite selectivity for Hg(2+) against other environmentally related metal ions. More significantly, this methodology displayed high reproducibility and acceptable accuracy, thus representing an optional sensing scheme for the screening of Hg(2+) in environmental water samples. PMID- 27179569 TI - Neonatal brain injury as a consequence of insufficient cerebral oxygenation. AB - Neonatal brain hypoxic-ischemic injury represents a serious health care and socio economical problem since it is one of the most common causes of mortality and morbidity of newborns. Neonatal hypoxic-ischemic encephalopathy is often associated with signs of perinatal asphyxia, with an incidence of about 2-4 per 1,000 live births and mortality rate up to 20%. In about one half of survivors, cerebral hypoxic-ischemic insult may result in more or less pronounced neuro psychological sequelae of immediate or delayed nature, such as seizures, cerebral palsy or behavioural and learning disabilities, including attention-deficit hyperactivity disorder. Hypoxic-ischemic injury develops as a consequence of transient or permanent restriction of blood supply to the brain. Severity of hypoxic-ischemic encephalopathy varies depending on the intensity and duration of hypoxia-ischemia, on the type and size of the brain region affected, and on the maturity of the foetal/neonatal brain. Though a primary cause of hypoxic-ischemic injury is lack of oxygen in the neonatal brain, underlying mechanisms of subsequent events that are critical for developing hypoxic-ischemic encephalopathy are less understood. Their understanding is however necessary for elaborating effective management for newborns that underwent cerebral hypoxic ischemic insult and thus are at risk of a negative outcome. The present paper summarizes current knowledge on cerebral hypoxic-ischemic injury of the neonate, fundamental processes involved in etiopathogenesis, with a special focus on cellular and molecular mechanisms and particular attention on certain controversial aspects of oxidative stress involvement. PMID- 27179570 TI - The cumulative effect of bisphosphonates and statins on stress fractures. Is it a failure of steroid biosynthesis? Case Report. AB - Osteoporosis related fractures pose a significant economic and healthcare problem. There is a growing concern about increased numbers of stress or low energy fractures after bisphosphonates therapy. A 65-year-old woman is presented with a stress fracture of the left femur. From our point of view, this fracture was associated with a long-term statin and bisphosphonate therapy. We did not find a similar presentation in medical literature. PMID- 27179571 TI - Changes in levels of oxidative stress markers and some neuronal enzyme activities in cerebrospinal fluid of multiple sclerosis patients. AB - OBJECTIVES: The aim of the present study was to assess cerebrospinal fluid (CSF) levels of malondialdehyde (MDA), F2 isoprostanes (8-iso-PGF2alpha) and total antioxidant status (TAS) in relapsing-remitting (RR) and secondary progressive (SP) course of MS and neurological controls. These parameters were correlated with brain tissue damage parameters - neuron-specific enolase and 3',5'-cAMP phosphodiesterase (PDE) in CSF. METHODS: CSF samples were obtained from MS patients divided into two groups according to the disease severity (EDSS) - RR and SP course of MS. Control group composed of neurological diagnoses without demyelination and neurodegeneration. 8-iso-PGF2alpha and NSE levels in the CSF samples were determined using specific immunochemistry assays. MDA levels in the CSF were measured by HPLC method after reaction with thiobarbituric acid in acidic conditions. TAS and total PDE activity of CSF was determined spectrophotometrically. RESULTS: There were significant differences in CSF MDA levels between MS group and controls and also between RR and SP disease course. By contrast, CSF levels of 8-iso-PGF2alpha in MS group and both forms of MS were comparable to control values. In addition, the results show increased CSF levels of PDE in MS group and no changes of NSE in CSF between MS and control group. CONCLUSION: These findings point to a possibility of using the parameters of different specificity to lipid peroxidation for monitoring different stages (acute/progressive) of MS. This study support the idea, that combination of CSF markers is important for monitoring overall brain tissue pathology in MS. PMID- 27179572 TI - Pediatric Lyme Neuroborreliosis: Different clinical presentations of the same agent; Single center experience. AB - OBJECTIVES: Lyme disease is a vector-associated infectious disease, caused by the agent, spirochete Borrelia burgdorferi. Neurologic findings are observed in approximately 12% of the cases and termed Lyme neuroborreliosis (LNB). Lyme neuroborreliosis may manifest with different clinical neurologic manifestations. METHODS: The study was conducted at tertiary training and research hospital. From January 2014 to September 2015, a total of 75 patients diagnosed with encephalitis, ataxia, Guillain Barre Syndrome (GBS), facial paralysis, acute disseminated encephalomyelitis (ADEM), pseudotumorcerebri were evaluated for inclusion to the study. Among these patients whom investigations of B. burgdorferi antibody IgM and/or IgG ELISA and Western Blot (WB) were detected to be positive, were assessed. Epidemiologic data, tick bite histories, duration of symptoms, clinical findings, radiologic findings, treatment durations and prognosis were investigated. RESULTS: Totally 7 patients had been treated with the diagnosis of Lyme neuroborreliosis. The mean age was 9.14+/-4.91 years; duration of symptoms before admission was 8.0+/-4.50 days; and the duration of antibiotic use was 2.85+/-0.89 weeks. All patients had received ceftriaxone and intravenous immunoglobulin (IVIG); 3 patients had received plasmapheresis (42.9%) and one patient had received pulse corticosteroid therapy. While the patient with the diagnosis of encephalomyeloneuritis and atypical GBS had partially improved, the other patients were completely cured. CONCLUSION: In this article, we report pediatric LNB patients, B. burgdorferi should also be considered in patients with atypical or severe neurologic involvement or a history of tick bite; it is known that the prognosis is good with appropriate and early treatment. PMID- 27179573 TI - Biochemical manifestations of the nervous tissue degradation after the blood brain barrier opening or water intoxication in rats. AB - OBJECTIVES: The aim of the study was to determine changes of biomarkers of nervous tissue degradation in experimental model of osmotic blood-brain barrier opening or water intoxication and to find whether they correspond to changes in well defined clinical entities. METHODS: In the cerebro-spinal fluid taken via the suboccipital puncture, myelin basic protein (MBP ng/ml), neuron-specific enolase (NSE ng/ml) and TAU-protein (Tau pg/ml) were determined by ELISA in 19 controls and 29 experimental rats several hours or one week after the experimental intervention. RESULTS: Significant difference between the control and experimental groups was revealed only for the concentration of myelin basic protein. After the BBB opening, its level dramatically increased within hours and dropped back to control values within one week. Water intoxication induced only dilutional hypoproteinorachia. No significant changes were found in NSE and levels of TAU-protein were not detectable. CONCLUSION: 1. Increased permeability of cytoplasmic membranes induced by water intoxication does not alter any of monitored CSF biomarkers. 2. Osmotic opening of the BBB in vivo experiment without the presence of other pathological conditions leads to a damage of myelin, without impairment of neurons or their axons. PMID- 27179574 TI - Thyroid-stimulating hormone acutely increases monocyte gene expression in vivo. AB - OBJECTIVES: Thyroid-stimulating hormone (TSH) acts in an extra-thyroidal fashion and induces a pro-inflammatory, pro-coagulant state. Blood monocytes can be activated by vascular stress, but it is not known if this occurs upon TSH administration. Our aim was to determine if recombinant human (rh) TSH, administered acutely to patients being screened for thyroid cancer recurrence, alters blood monocyte gene expression. DESIGN AND SETTING: Patients (14 women, 1 man) had a mean (+/-SD) age of 48+/-10 years, a body mass index of 26+/-6 kg/m2, a history of total thyroidectomy and radioablation for thyroid cancer, and were on L-thyroxine therapy at a university teaching hospital. They received 2 intramuscular doses of rhTSH (0.9 mg), administered on days 1 and 2. Blood samples were obtained at baseline on day1, and on days 3 and 5. RESULTS: Monocyte MCP-1 mRNA (mean+/-SE) increased significantly by 1.7+/-0.3 fold on day 5 following rhTSH stimulation (p=0.03, n=15). IL-1beta and CD36 mRNA expression also increased on day 5 (1.9+/-0.4 fold, p=0.07, n=14) and 2.5+/-0.4 fold, p=0.1, n=10), respectively, although did not quite reach statistical significance. Significant correlations were detected between the BMI of patients and their TSH stimulated monocyte mRNA responses at day 5 for CD11a, (r=0.66, n=14, p=0.01); CD14 (r=0.638, n=13, p=0.019), and CD16, r=0.84, n=13, p=0.0003). CONCLUSION: TSH administration increases pro-atherogenic monocyte gene expression. PMID- 27179575 TI - Comparison of relative telomere length measured in aortic tissue and leukocytes in patients with end stage heart failure. AB - OBJECTIVES: Telomeres are repetitive non-coding DNA sequences on the ends of eukaryotic chromosomes. Relative leukocyte telomere length (LrTL) is considered to reflect biological ageing and fitness. Therefore, we examined whether LrTL would reflect rTL in aortic tissue (ArTL) and whether it could be used as a marker of biological heart age. DESIGN: We analysed telomere length in aortic and leukocyte samples from 73 heart recipients (63 males, 10 females; age 52.2+/-11.7 years). Relative telomere length was measured using a quantitative PCR-based method. RESULTS: Neither LrTL nor ArTL correlated significantly with the age of heart recipients. Mean ArTL was slightly shorter than LrTL (p=0.06) and there was a slight but significant inverse correlation between LrTL and ArTL (p=0.019). CONCLUSIONS: The age of patients with end stage heart failure was not associated with leukocyte or aortic telomere length. An inverse correlation between LrTL and ArTL suggests that LrTL is unlikely to be an important predictor of biological ageing in these patients. PMID- 27179576 TI - Assessment of the effects of oseltamivir and indomethacin on dopamine, 5-HIAA, and some oxidative stress markers in stomach and brain of Salmonella typhimurium infected rats. AB - OBJECTIVES: The purpose of this study was to measure the effect of oseltamivir and indomethacin on dopamine and 5-HIAA levels and some oxidative biomarkers in brain and stomach of young rats in conditions of infection. METHODS: Female Sprague Dawley rats in absence or presence of a live culture of Salmonella typhimurium (S.Typh), were treated as follows: PBS, group 1 (control); oseltamivir (100 mg/kg), group 2; indomethacin (67 ug/kg) group 3; oseltamivir (100 mg/kg) + indomethacin (67 ug/kg), group 4. The drugs were administered intraperitoneally every 24 hr for 5 days while S. Typh was give orally in the first and third day. C-reactive proteins was measured in blood on sacrifice, and from brain extract, dopamine and 5-HIAA levels as well as GSH, calcium, and H2O2 and total ATPase activity were measured by validated methods. RESULTS: Dopamine increased significantly in cortex and cerebellum/medulla oblongata of groups that received indomethacin and oseltamivir. 5-HIAA increased significantly in all groups that received S.Typh. H2O2 decreased significantly in cortex regions of animals that received oseltamivir and indomethacin in presence of S.Typh. Total ATPase increased significantly in cortex and hemispheres of groups that received oseltamivir as well as in cerebellum/medulla oblongata and stomach of animals that received oseltamivir and indomethacin combined with S.Typh. GSH increased and calcium decreased significantly in stomach of animals that received oseltamivir or indomethacin alone or combined with S.Typh. CONCLUSION: These results demonstrate the association between inflammatory response, oxidative stress, dopaminergic, and serotonergic metabolism in an experimental inflammatory animal model. PMID- 27179577 TI - Multi-infarct dementia and Alzheimer disease, contribution of cerebral circulation ultrasonography to pathogenesis and differential diagnosis. Value of microembolisation. AB - OBJECTIVES: Dementias are one of the most serious health and socioeconomic issues. Multi-infarct dementia (MID) and Alzheimer's type dementia (AD) exhibit differences in cerebrovascular blood flow velocity profiles and in presence of microemboli, detected by transcranial Doppler sonography. MATERIAL AND METHODS: A group of 77 persons was divided into 4 subgroups: 1. subgroup of patients with MID (n=19; 10 male and 9 female, mean age was 74.32+/-8.30 years); 2. subgroup of patients with AD (n=19; 11 male and 8 female, mean age was 70.37+/-87.85 years); 3. subgroup of patients with hypertension (n=19; 11 male and 8 female, age adjusted) and 4. sex and age adjusted control group (CG) of 20 persons without hypertension or other serious risk factors. The duplex ultrasonographic examination of extracranial and intracranial circulation was preceded by neurologic, neuropsychological and psychiatric examination. The presence of microemboli was determined using Multi Dop X2 device (maker DWL), 60 minutes monitoring. All patients underwent brain computer tomography (CT) or magnetic resonance imaging (MRI). RESULTS: We found significantly higher incidence (68.4%, p=0.5267) of asymptomatic microemboli in ACM in the group of patients with MID compared to the AD group, the group of patients with hypertension and CG. CONCLUSION: The occurrence of "asymptomatic" emboli in the middle cerebral artery in patients with multi-infarct dementia is higher in the current study. Although these microemboli do not cause immediate symptoms, the evidence suggests, that they may be a risk factor for cognitive impairment, especially for multi-infarct dementia. PMID- 27179578 TI - Methylenotetrahydrololate reductase A1298C and C677T polymorphisms and adverse pregnancy outcome in women with PCOS. AB - OBJECTIVES: The aim of this study was to compare SNP C677T and A1298C in the MTHFR gene and pregnancy outcome in PCOS women. STUDY DESIGN: We investigated 76 PCOS and 56 non-PCOS women. Among PCOS patients 63 were women with a history of recurrent pregnancy loss (RPL) and 13 women were infertile. In non-PCOS group 40 women were RPL and 16 were infertile. We investigated the relationship between SNP in the MTHFR gene and pregnancy loss, homocysteine and AMH concentration in the study groups. RESULTS: DNA analysis of the PCOS and non-PCOS groups for MTHFR C677T and A1298C polymorphism showed no significant association between the groups. We demonstrated an increased miscarriage rate in non-PCOS women with A1298C polymorphism in the MTHFR gene (p=0.042). We found that homocysteine concentration was higher in women with SNP MTHFR A1298C (p=0.046). Moreover, we did not observe any association between the level of homocysteine and the pregnancy outcome in the whole study group. CONSLUSION: It seems that the presence of the MTHFR mutation is not associated with PCOS in the Polish population. However, our results may suggest a correlation between the MTHFR A1298C mutation and RPL in the non-PCOS group. PMID- 27179579 TI - Botulinum toxin treatment of freezing of gait in Parkinson's disease patients as reflected in functional magnetic resonance imaging of leg movement. AB - BACKGROUND: Freezing of gait (FOG) is a common disabling symptom of (in) Parkinson's disease (PD). The mechanism of FOG is (in) not clearly understood. We investigated the clinical effect and changes of the activity of the sensorimotor system using repeated functional MRI (fMRI) before and after application of botulinum toxin in Parkinson's disease patients with FOG. METHODS: We investigated 20 patients with PD, 10 with FOG and 10 without FOG. PD patients with FOG were treated with intramuscular application of botulinum toxin type A into the tensor fasciae latae muscle bilaterally. The clinical effect of treatment was assessed using FOG questionnaire, "Time up and go" test, UPDRS, Hoehn and Yahr staging, Clinical global impression scale. Activation of the sensorimotor system was studied using BOLD fMRI of the whole brain during repetitive abduction - adduction of each leg interleaved with rest. The clinical (in the FOG group) and imaging (in both groups) examination was repeated after a four-week interval. RESULTS: In the FOG group, the FOG questionnaire has shown a decline of scores after application of botulinum toxin that suggests possible effect of botulinum toxin on freezing of gait. In fMRI results, both groups manifested reduction of the sensorimotor network activated with leg movement, however, the FOG group also showed increased activation in cerebellar vermis and nuclei, in dorsal pons and in medulla after treatment. CONCLUSION: Alleviation of the FOG in PD patients by botulinum toxin seems to be reflected in the functional participation of the cerebellum and its projections as seen by fMRI. PMID- 27179580 TI - Systemic lupus erythematosus and renal tubular acidosis associated with hyperthyroidism. Case Report. AB - A case of a 42-year-old female with hyperthyroidism was subsequently diagnosed to have systemic lupus erythematosus with distal RTA. The clinical examination on admission showed swelling of the knee joints and the urinalysis showed pH 6.5, pro 3+. Her blood routine results were as follows: white blood cells 1.85*109/L, platelets 100*109/L, erythrocyte 3.06*1012/L. The serum potassium was 3.11 mmol/L, 24 hour urinary electrolyte: K 68.87 mmol/24 H, antinuclear antibodies (ANA) 1:1 000, speckled pattern. The anti-double stranded DNA antibody (anti dsDNA), anti SS-A(52) antibody and anti SS-A(60) antibody were positive. The light microscopy and immunofluorescence showed diffuse proliferative lupus nephritis. These data were compatible with the diagnosis of systemic lupus erythematosus. The diagnosis of hyperthyroidism and distal RTA is clear. This report showed that other autoimmune disease in the diagnosis of hyperthyroidism should not be ignored. PMID- 27179581 TI - The lesson of ankle-brachial index for long-term clinical outcomes: Time is not a line, but a series of now-points. PMID- 27179582 TI - The impact of growth promoters on muscle growth and the potential consequences for meat quality. AB - To meet the demands of increased global meat consumption, animal production systems will have to become more efficient, or at least maintain the current efficiency utilizing feed ingredients that are not also used for human consumption. Use of growth promoters is a potential option for increasing production animal feed efficiency and increased muscle growth. The objective of this manuscript is to describe the mechanisms by which the growth promoters, beta adrenergic agonists and growth hormone, mediate their effects, with specific consideration of the aspects which have implications for meat quality. PMID- 27179583 TI - Clostridia in the gut and onset of atopic dermatitis via eosinophilic inflammation. PMID- 27179584 TI - Depleted and enriched uranium exposure quantified in former factory workers and local residents of NL Industries, Colonie, NY USA. AB - BACKGROUND: Between 1958 and 1982, NL Industries manufactured components of enriched (EU) and depleted uranium (DU) at a factory in Colonie NY, USA. More than 5 metric tons of DU was deposited as microscopic DU oxide particles on the plant site and surrounding residential community. A prior study involving a small number of individuals (n=23) indicated some residents were exposed to DU and former workers to both DU and EU, most probably through inhalation of aerosol particles. OBJECTIVES: Our aim was to measure total uranium [U] and the uranium isotope ratios: (234)U/(238)U; (235)U/(238)U; and (236)U/(238)U, in the urine of a cohort of former workers and nearby residents of the NLI factory, to characterize individual exposure to natural uranium (NU), DU, and EU more than 3 decades after production ceased. METHODS: We conducted a biomonitoring study in a larger cohort of 32 former workers and 99 residents, who may have been exposed during its period of operation, by measuring Total U, NU, DU, and EU in urine using Sector Field Inductively Coupled Plasma - Mass Spectrometry (SF-ICP-MS). RESULTS: Among workers, 84% were exposed to DU, 9% to EU and DU, and 6% to natural uranium (NU) only. For those exposed to DU, urinary isotopic and [U] compositions result from binary mixing of NU and the DU plant feedstock. Among residents, 8% show evidence of DU exposure, whereas none shows evidence of EU exposure. For residents, the [U] geometric mean is significantly below the value reported for NHANES. There is no significant difference in [U] between exposed and unexposed residents, suggesting that [U] alone is not a reliable indicator of exposure to DU in this group. CONCLUSIONS: Ninety four percent of workers tested showed evidence of exposure to DU, EU or both, and were still excreting DU and EU decades after leaving the workforce. The study demonstrates the advantage of measuring multiple isotopic ratios (e.g., (236)U/(238)U and (235)U/(238)U) over a single ratio ((235)U/(238)U) in determining sources of uranium exposure. PMID- 27179586 TI - Controlling the burst release of amorphous drug-polysaccharide nanoparticle complex via crosslinking of the polysaccharide chains. AB - High-payload amorphous drug-polysaccharide nanoparticle complex (or nanoplex in short) represents a new class of supersaturating drug delivery systems intended for bioavailability enhancement of poorly-soluble drugs. Not unlike other nanoscale amorphous formulations, the nanoplex exhibits fast dissolution characterized by a burst drug release pattern. While the burst release is ideal for supersaturation generation in the presence of crystallization inhibitor, it is not as ideal for passive targeting drug delivery applications in which the nanoplex must be delivered by itself. Herein we developed nanoplex exhibiting controlled release via crosslinking of the polysaccharide chains onto which the drug molecules were electrostatically bound to. Curcumin and chitosan were used, respectively, as the drug and polysaccharide models with amine-reactive disuccinimidyl tartrate as the crosslinking agent. The crosslinked nanoplex exhibited improved morphology (i.e. smaller size, more spherical, and higher uniformity) that signified its more condensed structure. A twenty-fold reduction in the initial burst release rate with a threefold reduction in the overall dissolution rate was obtained after crosslinking. The slower dissolution was attributed to the more condensed structure of the crosslinked nanoplex that enhanced its dissociation stability in phosphate buffered saline. The reduction in the dissolution rate was proportional to the degree of crosslinking that was governed by the crosslinker to amine ratio. The crosslinking caused slight reductions in the payload and zeta potential of the nanoplex, but with no adverse effect on the cytotoxicity. This proof-of-concept study successfully demonstrated the use of polysaccharide crosslinking to control the drug release from high payload amorphous drug nanoplex. PMID- 27179585 TI - Maternal serum perfluoroalkyl substances during pregnancy and duration of breastfeeding. AB - BACKGROUND: Perfluoroalkyl substances (PFAS) may affect breast development and decrease duration of breastfeeding, thus interfering with the health benefits of breastfeeding. We investigated the association between maternal PFAS exposure and breastfeeding duration. METHODS: We measured PFAS concentrations in maternal serum collected during pregnancy in 2003-2006. After delivery, women (n=336) completed standardized breastfeeding surveys every 3 months until ending breastfeeding or 36 months postpartum. We estimated relative risks (RRs) for ending any breastfeeding within 3-6 months postpartum by Poisson regression, adjusted for relevant confounding factors. RESULTS: Women in the 4th quartile of perfluorooctanoic acid (PFOA) serum concentration had 1.77 times the risk of ending any breastfeeding by 3 months (95% confidence interval (CI): 1.23, 2.54; p trend=0.003) and 1.41 times the risk of ending any breastfeeding by 6 months (95%CI: 1.06, 1.87; p-trend=0.038), compared with women in the first quartile. Women in the 4th quartile of perfluorooctane sulfonic acid serum concentration had a marginally increased risk of discontinuing any breastfeeding by 3 months (RR=1.32; 95%CI: 0.97, 1.79; p-trend=0.065). CONCLUSIONS: Maternal serum PFOA concentrations were inversely related to duration of any breastfeeding in this cohort, even after controlling for prior breastfeeding. These findings suggest that PFOA exposure may adversely affect breastfeeding duration and highlight the need to consider the potential adverse effects of maternal environmental chemical exposure on breastfeeding. PMID- 27179587 TI - Development, preclinical safety, formulation, and stability of clinical grade bevacizumab-800CW, a new near infrared fluorescent imaging agent for first in human use. AB - There is a dire need for better visualization of cancer and analysis of specific targets in vivo. Molecular imaging with fluorescence is gaining more and more attention, as it allows detection of these targets and has advantages over radioactivity, such as no radiation dose, and lower costs. A key challenge in optical imaging however, is translation of the newly developed tracers from pre clinical phase to clinical application. We describe the development and safety testing of clinical grade bevacizumab-800CW, an antibody-based targeted agent for non-invasive imaging of vascular endothelial growth factor A (VEGF-A). Development included implementing the manufacturing process and analytical methods according to current Good Manufacturing Practice (cGMP), formulation studies, extended characterization and stability testing. For safety pharmacology an extended single dose toxicity study in mice was performed. Bevacizumab-800CW was formulated in isotonic phosphate buffered sodium chloride solution at pH 7. The production was robust and showed a reproducible labeling efficiency, and no impurities. The binding affinity to VEGF-A remained intact. The optimized product meets all release specifications, is stable up to at least 3months and its characteristics did not significantly differ from the unlabeled bevacizumab. Toxicity testing in mice showed no remarkable findings. In conclusion, sterile bevacizumab-800CW (6mg=6ml) can be produced in stock according to current Good Manufacturing Practice. It is ready for first-in-human use. PMID- 27179588 TI - Dried blood spots analysis with mass spectrometry: Potentials and pitfalls in therapeutic drug monitoring. AB - Therapeutic drug monitoring (TDM) relays in the availability of specialized laboratory assays, usually available in reference centers that are not accessible to all patients. In this context, there is a growing interest in the use of dried blood spot (DBS) sampling, usually obtained from finger pricks, which allows simple and cost-effective logistics in many settings, particularly in Developing Countries. The use of DBS assays to estimate plasma concentrations is highly dependent on the hematocrit of the blood, as well as the particular characteristics of the measured analyte. DBS assays require specific validation assays, most of them are related to hematocrit effects. In the present manuscript, the application of mass spectrometric assays for determination of drugs for TDM purposes in the last ten years is reviewed, as well as the particular validation assays for new DBS methods. PMID- 27179589 TI - Caenorhabditis elegans AGXT-1 is a mitochondrial and temperature-adapted ortholog of peroxisomal human AGT1: New insights into between-species divergence in glyoxylate metabolism. AB - In humans, glyoxylate is an intermediary product of metabolism, whose concentration is finely balanced. Mutations in peroxisomal alanine:glyoxylate aminotransferase (hAGT1) cause primary hyperoxaluria type 1 (PH1), which results in glyoxylate accumulation that is converted to toxic oxalate. In contrast, glyoxylate is used by the nematode Caenorhabditis elegans through a glyoxylate cycle to by-pass the decarboxylation steps of the tricarboxylic acid cycle and thus contributing to energy production and gluconeogenesis from stored lipids. To investigate the differences in glyoxylate metabolism between humans and C. elegans and to determine whether the nematode might be a suitable model for PH1, we have characterized here the predicted nematode ortholog of hAGT1 (AGXT-1) and compared its molecular properties with those of the human enzyme. Both enzymes form active PLP-dependent dimers with high specificity towards alanine and glyoxylate, and display similar three-dimensional structures. Interestingly, AGXT 1 shows 5-fold higher activity towards the alanine/glyoxylate pair than hAGT1. Thermal and chemical stability of AGXT-1 is lower than that of hAGT1, suggesting temperature-adaptation of the nematode enzyme linked to the lower optimal growth temperature of C. elegans. Remarkably, in vivo experiments demonstrate the mitochondrial localization of AGXT-1 in contrast to the peroxisomal compartmentalization of hAGT1. Our results support the view that the different glyoxylate metabolism in the nematode is associated with the divergent molecular properties and subcellular localization of the alanine:glyoxylate aminotransferase activity. PMID- 27179590 TI - Identifying intrinsically disordered protein regions likely to undergo binding induced helical transitions. AB - Many proteins contain intrinsically disordered regions (IDRs) lacking stable secondary and ordered tertiary structure. IDRs are often implicated in macromolecular interactions, and may undergo structural transitions upon binding to interaction partners. However, as binding partners of many protein IDRs are unknown, these structural transitions are difficult to verify and often are poorly understood. In this study we describe a method to identify IDRs that are likely to undergo helical transitions upon binding. This method combines bioinformatics analyses followed by circular dichroism spectroscopy to monitor 2,2,2-trifluoroethanol (TFE)-induced changes in secondary structure content of these IDRs. Our results demonstrate that there is no significant change in the helicity of IDRs that are not predicted to fold upon binding. IDRs that are predicted to fold fall into two groups: one group does not become helical in the presence of TFE and includes examples of IDRs that form beta-strands upon binding, while the other group becomes more helical and includes examples that are known to fold into helices upon binding. Therefore, we propose that bioinformatics analyses combined with experimental evaluation using TFE may provide a general method to identify IDRs that undergo binding-induced disorder to-helix transitions. PMID- 27179591 TI - Clinical training in the rural setting: using photovoice to understand student experiences. AB - INTRODUCTION: Attracting and retaining healthcare providers in rural locations in the USA has been an issue for more than two decades. In response to this need, many health sciences education institutions in the USA have developed special programs to encourage students to become healthcare providers in rural locations. One approach is the use of community-based education experiences through rural track programs. Rural track programs seek to address the shortage of healthcare providers working in rural areas by nurturing and educating students interested in rural practice and primary care. Such programs serve both medical students and students of other health professions. Yet, little is known about student experiences in rural track programs. As such, this study aimed to generate discourse on student experiences in the rural training environment and gain insight into the impact of rural environments on student learning. METHODS: An exploratory qualitative analysis of medical and physician assistant student experiences in two rural medical education training programs was conducted using the photovoice methodology. Photovoice is a participatory research method combining photography with participant commentary and focus groups. RESULTS: Twenty-two third-year medical and six second-year physician assistant students participated in the study. Students noted that in their rural sites the learning environment extended beyond direct clinical teaching in four primary ways: (1) relationships with clinical faculty translated to a sense of meaningful participation in healthcare teams; (2) connections with community members outside of clinical settings led to increased awareness of healthcare concerns; (3) rural settings provided important space to reflect on their experiences; and (4) the importance of infrastructure was highlighted. Students also believed that diversity of occupation, education, attitude, and perception of medical care impact learning in rural environments. CONCLUSIONS: The photovoice participatory research methodology allowed for a deeper understanding of the aspects of the rural training experience that resonated most among students in real time, using visual representations of students' lived experiences as defined by the students. PMID- 27179592 TI - Evaluation of Apically Extruded Debris from Curved Root Canal Filling Removal Using 5 Nickel-Titanium Systems. AB - INTRODUCTION: This study evaluated the amount of apically extruded debris in the retreatment of curved root canals using different nickel-titanium (NiTi) systems: the ProTaper Universal Retreatment (Dentsply Maillefer, Ballaigues, Switzerland), Mtwo Retreatment (VDW, Munich, Germany), D-Race Retreatment (FKG Dentaire, La Chaux-de-Fonds, Switzerland), R-Endo Retreatment (Micro-Mega, Besancon, France), and Reciproc (VDW) systems. METHODS: One hundred human mandibular premolars with curved root canals were prepared with the Reciproc #25 .08 NiTi system filled with AH Plus Jet (Dentsply DeTrey, Konstanz, Germany) sealer and gutta-percha and divided into 5 groups (n = 20). The canal filling was removed with the ProTaper, Mtwo, D-Race, and R-Endo retreatment systems and Reciproc instruments. Final preparation was done with the Reciproc #40 .06 NiTi system. Extruded debris was collected in preweighed Eppendorf tubes. The times required for retreatment were recorded. RESULTS: Reciproc produced significantly (P < .001) more debris than the other systems. ProTaper R and Mtwo R produced significantly (P < .001) more debris than D-Race and R-Endo. The Reciproc group required significantly (P < .001) less preparation time than the other groups. CONCLUSIONS: In the retreatment of curved root canals, the Reciproc system extruded significantly more debris than the rotary retreatment NiTi systems. In addition, the ProTaper and Mtwo retreatment systems extruded significantly more debris than the R-Endo and D-Race systems. The Reciproc system was significantly faster than the rotary retreatment systems. PMID- 27179593 TI - Evaluation of the Propidium Monoazide-quantitative Polymerase Chain Reaction Method for the Detection of Viable Enterococcus faecalis. AB - INTRODUCTION: One limitation of DNA-based molecular assays is their inability to distinguish between live and dead cells. A sample treatment with propidium monoazide (PMA) before DNA amplification has been proposed to overcome this problem. The aim of this in vitro study was to test different concentrations of PMA coupled with quantitative polymerase chain reaction (qPCR) for the detection of viable Enterococcus faecalis. METHODS: Viable or heat-killed suspensions of E. faecalis (106 colony-forming units/mL) were treated with PMA at 10, 50, and 100 MUg/mL before DNA extraction. qPCR was performed using primers complementary for E. faecalis 16S ribosomal RNA sequence. PMA was also tested on bacteria suspensions containing different proportions of viable and dead cells. Bacterial suspensions without PMA treatment were used as positive controls. RESULTS: The treatment of heat-killed suspensions with PMA at different concentrations significantly reduced the DNA amplification when compared with the group without treatment (P < .0001), indicating that DNA from dead cells was not used as templates. The greatest reduction in qPCR amplification of dead cell DNA was found when 100 MUg/mL PMA was used (P < .005). In mixtures containing live/dead cells, PMA allowed selective detection of viable cells. CONCLUSIONS: PMA was effective in inhibiting qPCR amplification from the DNA of dead cells, enabling in vitro detection and quantification of viable cells of E. faecalis. PMID- 27179594 TI - MicroRNAs serving as potential biomarkers and therapeutic targets in nasopharyngeal carcinoma: A critical review. AB - Despite significant medical advancement, nasopharyngeal carcinoma (NPC) remains one of the most difficult cancers to detect and treat where it continues to prevail especially among the Asian population. miRNAs could act as tumour suppressor genes or oncogenes in NPC. They play important roles in the pathogenesis of NPC by regulating specific target genes which are involved in various cellular processes and pathways. In particular, studies on miRNAs related to the Epstein Barr virus (EBV)-encoded latent membrane protein one (LMP1) and EBVmiRNA- BART miRNA confirmed the link between EBV and NPC. Both miRNA and its target genes could potentially be exploited for prognostic and therapeutic strategies. They are also important in predicting the sensitivity of NPC to radiotherapy and chemotherapy. The detection of stable circulating miRNAs in plasma of NPC patients has raised the potential of miRNAs as novel diagnostic markers. To conclude, understanding the roles of miRNA in NPC will identify ways to improve the management of patients with NPC. PMID- 27179595 TI - Distinct kinetics and mechanisms of mZVI particles aging in saline and fresh groundwater: H2 evolution and surface passivation. AB - Application of microscale zero-valent iron (mZVI) is a promising technology for in-situ contaminated groundwater remediation; however, its longevity is negatively impacted by surface passivation, especially in saline groundwater. In this study, the aging behavior of mZVI particles was investigated in three media (milli-Q water, fresh groundwater and saline groundwater) using batch experiments to evaluate their potential corrosion and passivation performance under different field conditions. The results indicated that mZVI was reactive for 0-7 days of exposure to water and then gradually lost H2-generating capacity over the next hundred days in all of the tested media. In comparison, mZVI in saline groundwater exhibited the fastest corrosion rate during the early phase (0-7 d), followed by the sharpest kinetic constant decline in the latter phases. The SEM EDS and XPS analyses demonstrated that in the saline groundwater, a thin and compact oxide film was immediately formed on the surface and significantly shielded the iron reactive site. Nevertheless, in fresh groundwater and milli-Q water, a passive layer composed of loosely and unevenly distributed precipitates slowly formed, with abundant reactive sites available to support continuous iron corrosion. These findings provide insight into the molecular-scale mechanism that governs mZVI passivation and provide implications for long-term mZVI application in saline contaminated groundwater. PMID- 27179596 TI - Purification of heavy metal loaded wastewater from electroplating industry under synthesis of delafossite (ABO2) by "Lt-delafossite process". AB - In this study we present a new, environmental friendly and economic method, called Lt-delafossite process to treat industrial wastewater (initial Cu(2+) concentrations of 1-15.6 g/l) by subsequent synthesis of nano-crystalline (doped) delafossite (CuFeO2) solely by precipitation and ageing at temperatures between 50 degrees C and 90 degrees C. The reached water purification rates are exclusively >=99.99% for both wastewater models and wastewaters from electroplating industry. We succeeded to synthesize a mixture of 3R and 2H delafossite at 50 degrees C after 90 h and >=70 degrees C after 16 h of ageing directly from industrial wastewater without any additional phases. In all cases green rust (GR), a Fe(II-III) layered double hydroxysulphate, Cu2O (cuprite) and Fe10O14(OH)2 (ferrihydrite) precipitates first. During ageing of the residues the metastable phases transform to delafossite. The residues are characterized by XRD, FTIR, SEM, TEM, VFTB and Mobetabauer measurements. PMID- 27179597 TI - Water disinfection using silver nanoparticle impregnated activated carbon: Escherichia coli cell-killing in batch and continuous packed column operation over a long duration. AB - Silver nanoparticles (Ag-NP) were selectively impregnated on the external surface of plasma treated activated carbon (AC) granules (referred to as Ag-AC hybrid, having 0.8 wt% of Ag), for achieving continuous disinfection of water in a single flow-column set-up. First, Ag-NPs (28 nm mean size) were synthesized by UV reduction. Subsequently, Escherichia coli cell-killing experiments were performed in both shake flask (i. e. batch-mode) and flow-column (i. e. continuous-mode) operations, using E. coli K12 (MTCC 1302) as a model organism. Batch results using 8 mg Ag-AC hybrid/ml of cell suspension showed that, 10(4) CFU/ml of cells were killed within 25 min contact time, with cell concentration decaying exponentially in time. Maintaining almost the same contact time as in the batch experiments, three columns packed with Ag-AC (all having a height of 25 cm but increasing diameters of 1, 5 and 8 cm, respectively) were used for monitoring cell-killing performance over a long duration. For all columns, inlet water having 10(4) CFU/ml E. coli could be completely disinfected to produce treated, outlet water having zero cell count. Specifically for the 8 cm diameter column, a maximum throughput of treating 1.62 L of contaminated water per hour could be maintained for at least up to 16 days. Moreover, the Ag concentration in the outlet water was only up to 29.8 MUg/L at steady state, which is well within the recommended limit of 100 MUg/L for drinking water. Hence, water disinfection for potable quality water (zero E. coli count and <100 MUg/L Ag) can be achieved in a continuous manner over a long duration, with our packed Ag-AC column. PMID- 27179598 TI - Supercritical water oxidation of Quinazoline: Effects of conversion parameters and reaction mechanism. AB - The supercritical water oxidation reaction of quinazoline and a set of related reaction products were investigated in batch reactors by varying the temperature (T, 400-600 degrees C), time (t, 0-400 s), water density (rho, 70.79-166.28 kg m(-3)) and oxidation coefficient (OC, 0-4.0). The TOC removal efficiency (CRE) increased significantly as the OC increased, whereas this effect was very limited at high OC (>2.0). Lack of oxygen resulted in low CRE and TN removal efficiency (NRE), also cause coke-formation, and giving high yield of NH3 and nitrogenous organic intermediates. Prolonging reaction time did not provide an appreciable improvement on CRE but remarkably increased NRE at temperature higher than 500 degrees C. Pyrimidines and pyridines as the nitrogenous intermediates were largely found in GC-MS spectrum. Polymerization among benzene, phenyl radical and benzyl radical played important roles in the formation of PAHs, such as naphthalene, biphenyl, phenanthrene. These collective results showed how the yield of intermediate products responded to changes in the process variables, which permitted the development of a potential reaction network for supercritical water oxidation of quinazoline. PMID- 27179599 TI - Rheumatoid arthritis and pulmonary nodules: An unexpected final diagnosis. AB - We report the case of a 50-year-old female smoker with an 11-year history of seropositive rheumatoid arthritis (rheumatoid factor and anti-cyclic citrullinated peptide antibodies) receiving triple therapy. She developed pulmonary nodules diagnosed as Langerhans cell histiocytosis by lung biopsy. We found no reported cases of the coexistence of these two diseases. Smoking abstinence led to radiologic resolution without modifying the immunosuppressive therapy. PMID- 27179600 TI - Beyond Cannabis: Plants and the Endocannabinoid System. AB - Plants have been the predominant source of medicines throughout the vast majority of human history, and remain so today outside of industrialized societies. One of the most versatile in terms of its phytochemistry is cannabis, whose investigation has led directly to the discovery of a unique and widespread homeostatic physiological regulator, the endocannabinoid system. While it had been the conventional wisdom until recently that only cannabis harbored active agents affecting the endocannabinoid system, in recent decades the search has widened and identified numerous additional plants whose components stimulate, antagonize, or modulate different aspects of this system. These include common foodstuffs, herbs, spices, and more exotic ingredients: kava, chocolate, black pepper, and many others that are examined in this review. PMID- 27179603 TI - Painting place: Re-imagining landscapes for older people's subjective wellbeing. AB - This study provides insights into how a participatory painting activity impacts older people's subjective wellbeing. The study uses qualitative methods to analyze the findings, and employs qualitative data collection methods to examine how creativity conducted in an environment of relational connectivity is beneficial to wellbeing. The findings demonstrate that processes of re-imagining landscape contribute to participants' retaining significant places in the mind when physical engagement is limited. The study reveals how the activity of re imagining landscape provokes emotions and memories that help participants connect the past with the present, and to connect their older and younger-age selves, positively to reaffirm their older age identity. The paper reflects on the intervention as a form of encounter with landscape whose benefits are potentially therapeutic for different groups, particularly those for whom engagement with memories may assist with processes of adaptation or transition. PMID- 27179602 TI - Fatty acid composition in serum correlates with that in the liver and non alcoholic fatty liver disease activity scores in mice fed a high-fat diet. AB - In this study, we investigated the correlation between the serum fatty acid composition and hepatic steatosis, inflammation, hepatocellular ballooning scores, and liver fatty acids composition in mice fed a high-fat diet. Livers were collected for non-alcoholic fatty liver disease score analysis. Fatty acid compositions were analysed by gas chromatography. Correlations were determined by Pearson correlation coefficient. Exposed to a high-fat diet, mice developed fatty liver disease with varying severity without fibrosis. The serum fatty acid variation became more severe with prolonged exposure to a high-fat diet. This variation also correlated significantly with the variation in livers, with the types of fatty acids corresponding to liver steatosis, inflammation, and hepatocellular ballooning scores. Results of this study lead to the following hypothesis: the extent of serum fatty acid variation may be a preliminary biomarker of fatty liver disease caused by high-fat intake. PMID- 27179601 TI - Heteromeric alpha7beta2 Nicotinic Acetylcholine Receptors in the Brain. AB - The alpha7 nicotinic acetylcholine receptor (alpha7 nAChR) is highly expressed in the brain, where it maintains various neuronal functions including (but not limited to) learning and memory. In addition, the protein expression levels of alpha7 nAChRs are altered in various brain disorders. The classic rule governing alpha7 nAChR assembly in the mammalian brain was that it was assembled from five alpha7 subunits to form a homomeric receptor pentamer. However, emerging evidence demonstrates the presence of heteromeric alpha7 nAChRs in heterologously expressed systems and naturally in brain neurons, where alpha7 subunits are co assembled with beta2 subunits to form a novel type of alpha7beta2 nAChR. Interestingly, the alpha7beta2 nAChR exhibits distinctive function and pharmacology from traditional homomeric alpha7 nAChRs. We review recent advances in probing the distribution, function, pharmacology, pathophysiology, and stoichiometry of the heteromeric alpha7beta2 nAChR, which have provided new insights into the understanding of a novel target of cholinergic signaling. PMID- 27179604 TI - Determinants and impact of suboptimal asthma control in Europe: The INTERNATIONAL CROSS-SECTIONAL AND LONGITUDINAL ASSESSMENT ON ASTHMA CONTROL (LIAISON) study. AB - BACKGROUND: According to the Global Initiative of Asthma, the aim of asthma treatment is to gain and maintain control. In the INTERNATIONAL CROSS-SECTIONAL AND LONGITUDINAL ASSESSMENT ON ASTHMA CONTROL (LIAISON) study, we evaluated the level of asthma control and quality of life (QoL), as well as their determinants and impact in a population consulting specialist settings. METHODS: LIAISON is a prospective, multicentre, observational study with a cross-sectional and a 12 month longitudinal phase. Adults with an asthma diagnosis since at least 6 months, receiving the same asthma treatment in the 4 weeks before enrolment were included. Asthma control was assessed with the 6-item Asthma Control Questionnaire (ACQ) and QoL with the MiniAsthma Quality of Life Questionnaire (MiniAQLQ). RESULTS: Overall, 8111 asthmatic patients were enrolled in 12 European countries. Asthma control was suboptimal in 56.5 % of patients and it was associated with poorer asthma-related QoL, higher risk of exacerbations and greater consumption of healthcare resources. Variables associated with suboptimal control were age, gender, obesity, smoking and comorbidities. Major determinants of poor asthma control were seasonal worsening and persisting exposure to allergens/irritants/triggers, followed by treatment-related issues. CONCLUSIONS: The cross-sectional phase results confirm that suboptimal control is frequent and has a high individual and economic impact. TRIAL REGISTRATION: The clinicaltrials.gov identifier is NCT01567280 . PMID- 27179605 TI - Prediction of brain maturity in infants using machine-learning algorithms. AB - Recent resting-state functional MRI investigations have demonstrated that much of the large-scale functional network architecture supporting motor, sensory and cognitive functions in older pediatric and adult populations is present in term- and prematurely-born infants. Application of new analytical approaches can help translate the improved understanding of early functional connectivity provided through these studies into predictive models of neurodevelopmental outcome. One approach to achieving this goal is multivariate pattern analysis, a machine learning, pattern classification approach well-suited for high-dimensional neuroimaging data. It has previously been adapted to predict brain maturity in children and adolescents using structural and resting state-functional MRI data. In this study, we evaluated resting state-functional MRI data from 50 preterm born infants (born at 23-29weeks of gestation and without moderate-severe brain injury) scanned at term equivalent postmenstrual age compared with data from 50 term-born control infants studied within the first week of life. Using 214 regions of interest, binary support vector machines distinguished term from preterm infants with 84% accuracy (p<0.0001). Inter- and intra-hemispheric connections throughout the brain were important for group categorization, indicating that widespread changes in the brain's functional network architecture associated with preterm birth are detectable by term equivalent age. Support vector regression enabled quantitative estimation of birth gestational age in single subjects using only term equivalent resting state-functional MRI data, indicating that the present approach is sensitive to the degree of disruption of brain development associated with preterm birth (using gestational age as a surrogate for the extent of disruption). This suggests that support vector regression may provide a means for predicting neurodevelopmental outcome in individual infants. PMID- 27179607 TI - Comparative in vitro study of cholinium-based ionic liquids and deep eutectic solvents toward fish cell line. AB - With the advent of ionic liquids, much was expected concerning their applicability as an alternative to organic solvents in the chemical technology and biotechnology fields. However, the most studied and commonly used ionic liquids based on imidazolium and pyridinium were found not to be as environmentally friendly as it was first expected. Therefore, a new generation of alternative solvents named natural ionic liquids and deep eutectic solvents, composed of natural and/or renewable compounds, have come into focus in recent years. Since the number of newly synthesized chemicals increases yearly, simple and reliable methods for their ecotoxicological assessment are necessary. Permanent fish cell lines can serve as a test system for the evaluation of a chemical's cytotoxicity. This paper presents research results on the cytotoxic effects on Channel Catfish Ovary (CCO) cell line induced by fifteen cholinium based ionic liquids and deep eutectic solvents. Based on the decrease in cell viability, the most obvious toxic effect on CCO cells was caused by ionic liquid choline oxalate, while other solvents tested exhibited low cytotoxicity. Therefore, we can conclude that cholinium-based ionic liquids and deep eutectic solvents are comparatively less toxic to CCO cells than conventional ionic liquids. PMID- 27179606 TI - Behavior, sensitivity, and power of activation likelihood estimation characterized by massive empirical simulation. AB - Given the increasing number of neuroimaging publications, the automated knowledge extraction on brain-behavior associations by quantitative meta-analyses has become a highly important and rapidly growing field of research. Among several methods to perform coordinate-based neuroimaging meta-analyses, Activation Likelihood Estimation (ALE) has been widely adopted. In this paper, we addressed two pressing questions related to ALE meta-analysis: i) Which thresholding method is most appropriate to perform statistical inference? ii) Which sample size, i.e., number of experiments, is needed to perform robust meta-analyses? We provided quantitative answers to these questions by simulating more than 120,000 meta-analysis datasets using empirical parameters (i.e., number of subjects, number of reported foci, distribution of activation foci) derived from the BrainMap database. This allowed to characterize the behavior of ALE analyses, to derive first power estimates for neuroimaging meta-analyses, and to thus formulate recommendations for future ALE studies. We could show as a first consequence that cluster-level family-wise error (FWE) correction represents the most appropriate method for statistical inference, while voxel-level FWE correction is valid but more conservative. In contrast, uncorrected inference and false-discovery rate correction should be avoided. As a second consequence, researchers should aim to include at least 20 experiments into an ALE meta analysis to achieve sufficient power for moderate effects. We would like to note, though, that these calculations and recommendations are specific to ALE and may not be extrapolated to other approaches for (neuroimaging) meta-analysis. PMID- 27179608 TI - Toxicity and mutagenicity of low-metallic automotive brake pad materials. AB - Organic friction materials are standardly used in brakes of small planes, railroad vehicles, trucks and passenger cars. The growing transportation sector requires a better understanding of the negative impact related to the release of potentially hazardous materials into the environment. This includes brakes which can release enormous quantities of wear particulates. This paper addresses in vitro detection of toxic and mutagenic potency of one model and two commercially available low-metallic automotive brake pads used in passenger cars sold in the EU market. The model pad made in the laboratory was also subjected to a standardized brake dynamometer test and the generated non-airborne wear particles were also investigated. Qualitative "organic composition" was determined by GC/MS screening of dichloromethane extracts. Acute toxicity and mutagenicity of four investigated sample types were assessed in vitro by bioluminescence assay using marine bacteria Vibrio fischeri and by two bacterial bioassays i) Ames test on Salmonella typhimurium His(-) and ii) SOS Chromotest using Escherichia coli PQ37 strain. Screening of organic composition revealed a high variety of organic compounds present in the initial brake pads and also in the generated non airborne wear debris. Several detected compounds are classified by IARC as possibly carcinogenic to humans, e. g. benzene derivatives. Acute toxicity bioassay revealed a response of bacterial cells after exposure to all samples used. Phenolic resin and wear debris were found to be acutely toxic; however in term of mutagenicity the response was negative. All non-friction exposed brake pad samples (a model pad and two commercial pad samples) were mutagenic with metabolic activation in vitro. PMID- 27179609 TI - miR-937 contributes to the lung cancer cell proliferation by targeting INPP4B. AB - Lung cancer is the leading cause of cancer death worldwide, microRNAs play critical role in the initiation and development of lung cancer. Here, we used MTT assay, colony formation assay, soft agar growth assay and BrdU incorporation assay to investigate miR-937's role in lung cancer. We found that miR-937 was upregulated in lung cancer tissues and cells. Overexpression of miR-937 in A549 promoted anchorage -dependent and -independent growth, whereas knockdown of miR 937 reduced this effect. Meanwhile, we also found miR-937 overexpression increased CCND1 and c-Myc levels in both mRNA and protein levels, knockdown of miR-937 reduced this effect, confirming miR-937 promoted cell proliferation. Mechanism analyses found polyphosphate 4-phosphatase type II (INPP4B) was the target of miR-937, miR-937 directly bound to the 3'UTR of INPP4B, knockdown of INPP4B in A549 with miR-937 inhibitor promoted anchorage -dependent and independent growth, suggesting miR-937 contributed to cell proliferation of lung cancer by inhibiting INPP4B, it might be a valuable target for lung cancer therapy. PMID- 27179610 TI - Analysing pseudoephedrine/methamphetamine policy options in Australia using multi criteria decision modelling. AB - BACKGROUND: In this paper we capture and synthesize the unique knowledge of experts so that choices regarding policy measures to address methamphetamine consumption and dependency in Australia can be strengthened. We examine perceptions of the: (1) influence of underlying factors that impact on the methamphetamine problem; (2) importance of various models of intervention that have the potential to affect the success of policies; and (3) efficacy of alternative pseudoephedrine policy options. METHODS: We adopt a multi-criteria decision model to unpack factors that affect decisions made by experts and examine potential variations on weight/preference among groups. Seventy experts from five groups (i.e. academia (18.6%), government and policy (27.1%), health (18.6%), pharmaceutical (17.1%) and police (18.6%)) in Australia participated in the survey. RESULTS: Social characteristics are considered the most important underlying factor, prevention the most effective strategy and Project STOP the most preferred policy option with respect to reducing methamphetamine consumption and dependency in Australia. One-way repeated ANOVAs indicate a statistically significant difference with regards to the influence of underlying factors (F(2.3, 144.5)=11.256, p<.001), effectiveness of interventions (F(2.4, 153.1)=28.738, p<.001) and policy options (F(2.8, 175.5)=70.854, p<.001). CONCLUSION: A majority of respondents believed that genetic, biological, emotional, cognitive and social factors are the most influential explanatory variables in terms of methamphetamine consumption and dependency. Most experts support the use of preventative mechanisms to inhibit drug initiation and delayed drug uptake. Compared to other policies, Project STOP (which aims to disrupt the initial diversion of pseudoephedrine) appears to be a more preferable preventative mechanism to control the production and subsequent sale and use of methamphetamine. This regulatory civil law lever engages third parties in controlling drug-related crime. The literature supports third-party partnerships as it engages experts who have knowledge and expertise with respect to prevention and harm minimization. PMID- 27179611 TI - Levosimendan for Heart Failure. PMID- 27179612 TI - Advances in Imaging for the Management of Acute Aortic Syndromes: Focus on Transesophageal Echocardiography and Type-A Aortic Dissection for the Perioperative Echocardiographer. PMID- 27179614 TI - Anesthetic Management of a Patient With Situs Inversus for Bilateral Orthotopic Lung Transplantation. PMID- 27179613 TI - Hemodynamic Testing of Patient-Specific Mitral Valves Using a Pulse Duplicator: A Clinical Application of Three-Dimensional Printing. AB - OBJECTIVE: To evaluate the feasibility of obtaining hemodynamic metrics of echocardiographically derived 3-dimensional printed mitral valve models deployed in a pulse-duplicator chamber. DESIGN: Exploratory study. SETTING: Tertiary-care university hospital. PARTICIPANTS: Percutaneous MitraClip procedure patient. INTERVENTIONS: Three-dimensional R-wave gated, full-volume transesophageal echocardiography images were obtained after deployment of the MitraClip device. A high-quality diastolic frame of the mitral valve was segmented using Mimics Innovation Suite and merged with a flange. The data were exported as a stereolithography (.stl) file, and a rigid 3-dimensional model was printed using a MakerBot Replicator 2 printer. A flexible silicone cast then was created and deployed in the pulse-duplicator chamber filled with a blood-mimicking fluid. MEASUREMENTS AND MAIN RESULTS: The authors were able to obtain continuous-wave Doppler tracings of the valve inflow with a transesophageal echocardiography transducer. They also were able to generate diastolic ventricular and atrial pressure tracings. Pressure half-time and mitral valve area were computed from these measurements. CONCLUSION: This pulse duplicator shows promising applications in hemodynamic testing of patient-specific anatomy. Future modifications to the system may allow for visualization and data collection of gradients across the aortic valve. PMID- 27179615 TI - Distributed semi-supervised support vector machines. AB - The semi-supervised support vector machine (S(3)VM) is a well-known algorithm for performing semi-supervised inference under the large margin principle. In this paper, we are interested in the problem of training a S(3)VM when the labeled and unlabeled samples are distributed over a network of interconnected agents. In particular, the aim is to design a distributed training protocol over networks, where communication is restricted only to neighboring agents and no coordinating authority is present. Using a standard relaxation of the original S(3)VM, we formulate the training problem as the distributed minimization of a non-convex social cost function. To find a (stationary) solution in a distributed manner, we employ two different strategies: (i) a distributed gradient descent algorithm; (ii) a recently developed framework for In-Network Nonconvex Optimization (NEXT), which is based on successive convexifications of the original problem, interleaved by state diffusion steps. Our experimental results show that the proposed distributed algorithms have comparable performance with respect to a centralized implementation, while highlighting the pros and cons of the proposed solutions. To the date, this is the first work that paves the way toward the broad field of distributed semi-supervised learning over networks. PMID- 27179616 TI - Binary classification SVM-based algorithms with interval-valued training data using triangular and Epanechnikov kernels. AB - Classification algorithms based on different forms of support vector machines (SVMs) for dealing with interval-valued training data are proposed in the paper. L2-norm and Linfinity-norm SVMs are used for constructing the algorithms. The main idea allowing us to represent the complex optimization problems as a set of simple linear or quadratic programming problems is to approximate the Gaussian kernel by the well-known triangular and Epanechnikov kernels. The minimax strategy is used to choose an optimal probability distribution from the set and to construct optimal separating functions. Numerical experiments illustrate the algorithms. PMID- 27179617 TI - Long-term epigenetic alterations in a rat model of Gulf War Illness. AB - Gulf War Illness (GWI) is a chronic, multisymptom illness that affects 25% of the 700,000 US veterans deployed to the Persian Gulf during the 1990-1991 Gulf War. Central nervous system impairments are among the most common symptoms reported, including memory dysfunction and depression. After 25 years, the diagnosis remains elusive, useful treatments are lacking, and the cause is poorly understood, although exposures to pyridostigmine bromide (PB) and pesticides are consistently identified to be among the strongest risk factors. Epigenetic changes including altered microRNA (miRNA) expression and DNA methylation play an important role in learning, memory, and emotion regulation and have been implicated in various neurological disorders. In this study, we used an established rat model of GWI to determine whether 1) chronic alterations in miRNA expression and global DNA methylation and DNA hydroxymethylation are mechanisms involved in the pathobiology of GWI, and 2) plasma exosome small RNAs may serve as potential noninvasive biomarkers of this debilitating disease. One year after a 28-day exposure regimen of PB, DEET (N,N-diethyl-3-methylbenzamide), permethrin, and mild stress, expression of 84 mature miRNAs and global 5 methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) content were analyzed in the brains of GWI rats and vehicle controls by PCR array and enzyme-linked immunosorbent assay, respectively. Plasma exosome RNA next-generation sequencing analysis was performed in pooled samples to discover potential noninvasive biomarkers. We found that combined exposure to low doses of GW-related chemicals and mild stress caused epigenetic modifications in the brain that persisted one year after exposure, including increased expression of miR-124-3p and miR-29b-3p in the hippocampus and regional alterations in global 5mC and 5hmC content. GW relevant exposures also induced the differential expression of two piwi interacting RNAs (piRNAs) in circulation (piR-007899 and piR-019162). Results from this study implicate a role for epigenetic alterations in GWI. Evaluation of the diagnostic potential of plasma exosome RNAs in veterans with GWI is warranted. PMID- 27179619 TI - Influences of recovery from wildfire and thinning on soil respiration of a Mediterranean mixed forest. AB - The ecosystem recovery after wildfire and thinning practices are both key processes that have great potential to influence fluxes and storage of carbon within Mediterranean semiarid ecosystems. In this study, started 7years after a wildfire, soil respiration (SR) patterns measured from 2008 to 2010 were compared between an unmanaged-undisturbed mature forest stand (UB site) and a naturally regenerated post-wildfire stand (B site) in a Mediterranean mixed forest in Spain. The disturbed stand included a control zone (unthinned forest, BUT site) and a thinned zone (BT site). Our results indicated that SR was lower at naturally regenerated after fire sites (BUT and BT) than at unburnt one. Soil under the canopy layer of pine and oak trees exhibited higher SR rates than bare or herbaceous layer soils, regardless of the site. The effect of thinning was only manifest, with a significant increase of SR, during the 1st year after thinning practices. SR showed a clear soil temperature-dependent seasonal pattern, which was strongly modulated by soil water content (SWC), especially in summer. Site-specific polynomial regression models were defined to describe SR responses, being mainly controlled by both soil temperature (Ts) and SWC at UB site, or Ts at burnt sites. The sensitivity of SR rate to Ts variations (Q10) ranged between 0.20 and 6.89, with mean annual values varying between 0.92 and 1.35. Q10 values were higher at BT than at UB-BUT sites. The results revealed a significant, non-linear dependence, of Q10 on both Ts and SWC at UB site, and on Ts at both burnt sites. This study contributes to (i) improve the understanding of how natural recovery and management practices affect soil respiration in a Mediterranean forest during their early stages after fire disturbance and (ii) highlight the importance of Q10 values <1 which emphasizes drought stress effect on SR temperature sensitivity. PMID- 27179620 TI - Modelling macronutrient dynamics in the Hampshire Avon river: A Bayesian approach to estimate seasonal variability and total flux. AB - The macronutrients nitrate and phosphate are aquatic pollutants that arise naturally, however, in excess concentrations they can be harmful to human health and ecosystems. These pollutants are driven by river currents and show dynamics that are affected by weather patterns and extreme rainfall events. As a result, the nutrient budget in the receiving estuaries and coasts can change suddenly and seasonally, causing ecological damage to resident wildlife and fish populations. In this paper, we propose a statistical change-point model with interactions between time and river flow, to capture the macronutrient dynamics and their responses to river flow threshold behaviour. It also accounts for the nonlinear effect of water quality properties via nonparametric penalised splines. This model enables us to estimate the daily levels of riverine macronutrient fluxes and their seasonal and annual totals. In particular, we present a study of macronutrient dynamics on the Hampshire Avon River, which flows to the southern coast of the UK through the Christchurch Harbour estuary. We model daily data for more than a year during 2013-14 in which period there were multiple severe meteorological conditions leading to localised flooding. Adopting a Bayesian inference framework, we have quantified riverine macronutrient fluxes based on input river flow values. Out of sample empirical validation methods justify our approach, which captures also the dependencies of macronutrient concentrations with water body characteristics. PMID- 27179618 TI - Complex translocation disrupting TCF4 and altering TCF4 isoform expression segregates as mild autosomal dominant intellectual disability. AB - BACKGROUND: Mutations of TCF4, which encodes a basic helix-loop-helix transcription factor, cause Pitt-Hopkins syndrome (PTHS) via multiple genetic mechanisms. TCF4 is a complex locus expressing multiple transcripts by alternative splicing and use of multiple promoters. To address the relationship between mutation of these transcripts and phenotype, we report a three-generation family segregating mild intellectual disability with a chromosomal translocation disrupting TCF4. RESULTS: Using whole genome sequencing, we detected a complex unbalanced karyotype disrupting TCF4 (46,XY,del(14)(q23.3q23.3)del(18)(q21.2q21.2)del(18)(q21.2q21.2)inv(18)(q21.2q21. )t(14;18)(q23.3;q21.2)(14pter(r)14q23.3::18q21.2(r)18q21.2::18q21.1(r)18qter;18pt r(r)18q21.2::14q23.3(r)14qter). Subsequent transcriptome sequencing, qRT-PCR and nCounter analyses revealed that cultured skin fibroblasts and peripheral blood had normal expression of genes along chromosomes 14 or 18 and no marked changes in expression of genes other than TCF4. Affected individuals had 12-33 fold higher mRNA levels of TCF4 than did unaffected controls or individuals with PTHS. Although the derivative chromosome generated a PLEKHG3-TCF4 fusion transcript, the increased levels of TCF4 mRNA arose from transcript variants originating distal to the translocation breakpoint, not from the fusion transcript. CONCLUSIONS: Although validation in additional patients is required, our findings suggest that the dysmorphic features and severe intellectual disability characteristic of PTHS are partially rescued by overexpression of those short TCF4 transcripts encoding a nuclear localization signal, a transcription activation domain, and the basic helix-loop-helix domain. PMID- 27179621 TI - Human Adaptive Natural Killer Cells: Beyond NKG2C. AB - Paradigm-shifting studies have identified NKG2C(+) adaptive natural killer (NK) cells in individuals infected with cytomegalovirus. Recently in Cell Reports, Liu et al. demonstrate that NKG2C(-/-) HCMV(+) individuals also generate adaptive NK cells, and reveal CD2 as a major co-stimulatory receptor for these NK cells specialized to respond via FcgammaRIIIa/CD16. PMID- 27179622 TI - Oxidative stress and hypoxia in normal and leukemic stem cells. AB - The main hematopoietic stem cell (HSC) functions, self-renewal and differentiation, are finely regulated by both intrinsic mechanisms such as transcriptional and epigenetic regulators and extrinsic signals originating in the bone marrow microenvironment (HSC niche) or in the body (humoral mediators). The interaction between regulatory signals and cellular metabolism is an emerging area. Several metabolic pathways function differently in HSCs compared with progenitors and differentiated cells. Hypoxia, acting through hypoxia-inducing factors, has emerged as a key regulator of stem cell biology and acts by maintaining HSC quiescence and a condition of metabolic dormancy based on anaerobic glycolytic energetic metabolism, with consequent low production reactive oxygen species (ROS) and high antioxidant defense. Hematopoietic cell differentiation is accompanied by changes in oxidative metabolism (decrease of anaerobic glycolysis and increase of oxidative phosphorylation) and increased levels of ROS. Leukemic stem cells, defined as the cells that initiate and maintain the leukemic process, show peculiar metabolic properties in that they are more dependent on oxidative respiration than on glycolysis and are more sensitive to oxidative stress than normal HSCs. Several mitochondrial abnormalities have been described in acute myeloid leukemia (AML) cells, explaining the shift to aerobic glycolysis observed in these cells and offering the unique opportunity for therapeutic metabolic targeting. Finally, frequent mutations of the mitochondrial isocitrate dehydrogenase-2 (IDH2) enzyme are observed in AML cells, in which the mutated enzyme acts as an oncogenic driver and can be targeted using specific inhibitors under clinical evaluation with promising results. PMID- 27179623 TI - Granulomatosis with polyangiitis (Wegener's granulomatosis) causing atlantoaxial instability: a case report. AB - BACKGROUND CONTEXT: No previous cases of atlantoaxial instability due to granulomatosis with polyangiitis have been reported. PURPOSE: The aim of this study was to report a case of granulomatosis with polyangiitis causing atlantoaxial instability. STUDY DESIGN: This is a case report. PATIENT SAMPLE: A 45-year-old woman participated in this study. OUTCOME MEASURES: The patient's pain and atlantoaxial instability were resolved. METHODS: A 45-year-old Caucasian woman with a large ulcerative lesion in her oropharynx initially presented with chronic sinusitis, pharyngitis, and severe odynophagia. Years after her original symptoms began, she developed neck pain radiating into her upper trapezial region and shoulders. RESULTS: Atlantoaxial fusion was performed on the patient, resolving her neck, upper trapezial, and shoulder pain. She was diagnosed with granulomatosis with polyangiitis (formerly Wegener's granulomatosis) and treated with cyclophosphamide. CONCLUSIONS: Granulomatosis with polyangiitis should be part of the working differential diagnosis for non-traumatic cervical spine injury. The atlantoaxial instability can be managed with stabilization, and the disease process itself can be treated with cyclophosphamide. PMID- 27179624 TI - Rare true-positive outcome of spinal cord monitoring in patients under age 4 years. AB - BACKGROUND CONTEXT: Intraoperative monitoring (IOM) is becoming an essential component in spinal surgery, but there are many different viewpoints about it in patients under age 4 years. PURPOSE: This study aims to report some IOM features in children under age 4 years. DESIGN/SETTING: This is a retrospective cases study. PATIENT SAMPLE: A total of 37 children (35.76 months+/-1.47) and 120 patients with adolescent idiopathic scoliosis (AIS, 14.2 years) were recruited between September 2012 and December 2014. OUTCOME MEASURES: Relevant monitoring changes were identified as transcranial motor evoked potentials (MEP) or somatosensory evoked potentials (SEP) loss associated with high-risk surgical maneuvers. METHODS: Motor evoked potential, SEP, and free-run electromyography (free-run EMG) were used for IOM. The IOM parameters (amplitude, latency, and waveform) and monitoring outcomes (signal changes, true positive, and false positive) were mainly analyzed in the patients under age 4 years. RESULTS: All young patients presented stable MEP (90.6 uV+/-20.3) and SEP (1.01 uV+/-0.3) baseline. The baseline success rate (100%) was the same as that in patients with AIS; however, the MEP amplitude of young patients was significantly lower than that of patients with AIS (90.6 uV+/-20.3 vs. 312.1 uV+/-25.2, n=120; **p<.01) under the same stimulus parameters. Moreover, children under age 4 years have more monitoring changes (18.9%, 7 of 37), but true-positive findings are rare (0%) in our population. CONCLUSIONS: Intraoperative monitoring baseline can be obtained satisfactorily in children under age 4 years, but true-positive findings are rare; meanwhile, low MEP amplitude and poor waveforms are common. PMID- 27179625 TI - Development of a clinically relevant impingement test method for a mobile bearing lumbar total disc replacement. AB - BACKGROUND CONTEXT: Total disc arthroplasty is an alternative therapy to spinal fusion for the treatment of neck or low back pain and is hypothesized to reduce the risk of disease progression to the adjacent spinal levels. Radiographic and retrieval analyses of various total disc replacements (TDRs) have shown evidence of impingement damage. Impingement of TDRs can occur when the device reaches the limits of its functional range of motion, causing contact between peripheral regions of the device. PURPOSE: Impingement can be associated with increased wear and mechanical damage; however, impingement conditions are not simulated in current standardized mechanical bench test methods. This study explored the test conditions necessary to apply clinically relevant impingement loading to a lumbar TDR in vitro. STUDY DESIGN: An experimental protocol was developed and evaluated using in vivo retrievals for qualitative and quantitative validation. METHODS: Retrieval analysis was conducted on a set of 11 size 3 retrieved Charite devices using American Society for Testing and Materials F561 as a guide. The impingement range of motion was determined using a combination of modeling and experiments, and was used as an input in vitro testing. A 1-million cycle in vitro test was then conducted, and the in vitro samples were characterized using methods similar to the retreived devices. RESULTS: All in vitro tested samples exhibited impingement regions and damage patterns consistent with retrieved devices. Consistent with the retrievals, the impingement damage on the rim was a combination of abrasive wear and plastic deformation. Micro computed tomography (microCT) was used to quantitatively assess rim damage due to impingement. Rim penetration was statistically lower in the retrievals when compared with both in vitro groups. Rim elongation was comparable among all groups. The simulated-facet group had statistically greater angular rim deformations than the retrieval group and the no-facet group. CONCLUSIONS: Results demonstrate that clinically relevant impingement seen on mobile bearings of lumbar TDRs can be replicated on the bench. PMID- 27179626 TI - Impact of gut microbiota on diabetes mellitus. AB - Various functions of the gut are regulated by sophisticated interactions among its functional elements, including the gut microbiota. These microorganisms play a crucial role in gastrointestinal mucosa permeability. They control the fermentation and absorption of dietary polysaccharides to produce short-chain fatty acids, which may explain their importance in the regulation of fat accumulation and the subsequent development of obesity-related diseases, suggesting that they are a crucial mediator of obesity and its consequences. In addition, gut bacteria play a crucial role in the host immune system, modulation of inflammatory processes, extraction of energy from the host diet and alterations of human gene expression. Dietary modulation of the human colonic microbiota has been shown to confer a number of health benefits to the host. Simple therapeutic strategies targeted at attenuating the progression of chronic low-grade inflammation and insulin resistance are urgently required to prevent or slow the development of diabetes in susceptible individuals. The main objective of this review is to address the pathogenic association between gut microbiota and diabetes, and to explore any novel related therapeutic targets. New insights into the role of the gut microbiota in diabetes could lead to the development of integrated strategies using probiotics to prevent and treat these metabolic disorders. PMID- 27179627 TI - Pharmacokinetics, biodistribution and excretion studies of neotuberostemonine, a major bioactive alkaloid of Stemona tuberosa. AB - Neotuberostemonine is a potent antitussive alkaloid extracted from Stemona tuberosa. However, the pharmacokinetics, tissue distribution and excretion of pure neotuberostemonine have not been reported. The present study was aimed to investigate the pharmacokinetic parameters of neotuberostemonine by developing an ultra-high performance liquid chromatography-tandem mass spectrometry method. Neotuberostemonine and tetrahydropalmatine (internal standard, IS) in bio-samples were extracted by protein precipitation with methanol and successfully separated on a Zorbax Extend C18 column by using a mobile phase of acetonitrile and a mixture of 0.1% formic acid and 5mM ammonium acetate. The detection was performed by using positive ion electrospray ionization in multiple reaction monitoring mode. The MS/MS ion transitions were monitored at m/z 376.1->302.0 for neotuberostemonine and 355.8->192.0 for IS. After oral administration of neotuberostemonine in rats, the Cmax and AUC0-infinity were 11.37ng/mL and 17.68ng.h/mL at 20mg/kg and 137.6ng/mL and 167.4ng.h/mL at 40mg/kg, and the t1/2 were 2.28 and 3.04h at 20 and 40mg/kg, respectively. The high neotuberostemonine concentrations were found in intestine, stomach and liver, and there was no long term accumulation of neotuberostemonine in tissues. Total recoveries of neotuberostemonine were only 0.90% (0.19% in bile, 0.05% in urine and 0.66% in feces), which might be resulted from the intestine and liver first-pass effects, indicating that neotuberostemonine may be mainly excreted as its metabolites. All above results would provide helpful information for the further pharmacological and clinical studies of neotuberostemonine and the crude drug. PMID- 27179629 TI - [Infective endocarditis by Streptococcus pluranimalium: Case report]. PMID- 27179628 TI - Frequencies of CYP2C9 polymorphisms in North Indian population and their association with drug levels in children on phenytoin monotherapy. AB - BACKGROUND: Phenytoin, mainly metabolized by cytochrome P450 enzyme system, has a narrow therapeutic index and may have adverse effects due to inter-individual variation in the dose requirement and genetic polymorphisms. This cross-sectional study was done to study the prevalence of cytochrome P450 CYP2C9 polymorphisms in Indian epileptic children and to see the effect of polymorphisms on serum levels in epileptic children on phenytoin monotherapy. METHODS: We studied 89 epileptic children of North Indian population, randomly selected, to see the genotypic and allelic frequency of CYP2C9 and its association with drug levels on phenytoin monotherapy. Analysis was done using STATA 9 Software. The results were analyzed as prevalence at 95 % C.I. (Confidence Interval). The difference in mean phenytoin serum levels between wild and mutant alleles was tested using Student's T test for independent samples. P value less than 0.05 was considered statistically significant. RESULTS: CYP2C9*1, *2 & *3 allelic frequencies were 85.4, 4.5 and 10.1 % respectively. CYP2C9*3 allelic group showed significantly higher serum phenytoin levels compared to the wild variants (P = 0.009). There was no statistically significant difference in the dose received (P = 0.12) and side effects of CYP2C9*2 and CYP2C9*3 genotypes (P = 0.442 and 0.597 respectively) when compared with wild variant. CONCLUSION: CYP2C9*3 is more common than *2 in the present study. All the polymorphisms demonstrated in our study were heterozygous with no homozygosity. Serum phenytoin levels are higher in polymorphic groups (*3) which suggest their poor metabolizing nature. Genotyping may help to avoid toxicity and concentration-dependent adverse effects. PMID- 27179630 TI - Does a polyaxial-locking system confer benefits for osteosynthesis of the distal fibula: A cadaver study. AB - BACKGROUND: In plate osteosynthesis involving the distal fibula, antiglide plating is superior to lateral plating in terms of the biomechanical properties. The goal of this study was to examine whether polyaxial-locking implants confer additional benefits in terms of biomechanical stability. METHODS: Seven pairs of human cadaveric fibulae were subjected to osteotomy in a standardized manner to simulate an uncomplicated Weber B fracture. The generated fractures were managed with a dorsolateral antiglide plate. To this end, one fibula of the pair was subjected to non-locking plating and the other to polyaxial-locking plating. Biomechanical tests included quantification of the primary bending and torsional stiffness. In addition, the number of cycles to failure in cyclic bending loading were determined and compared. Bone mineral density was measured in all specimens. RESULTS: Bone mineral density was comparable in both groups. Primary stability was higher in the polyaxial-locking group under torsional loading, and higher in the non-locking group under bending loading. The differences, however, were not statistically significant. All specimens except for one fixed-angle construct failed the cyclic loading test. The number of cycles to failure did not differ significantly between polyaxial-locking and non-locking fixation. CONCLUSION: In a cadaveric Weber B fracture model, we observed no differences in biomechanical properties between polyaxial-locking and non-locking fixation using an antiglide plate. Based on the biomechanical considerations, no recommendation can be made regarding the choice of the implant. Further biomechanical and clinical studies are required. CLINICAL RELEVANCE: Information on the behavior of polyaxial locking plates is relevant to surgeons performing internal fixation of distal fibula fractures. PMID- 27179631 TI - Effects of antidepressants on postmenopausal bone loss - A 5-year longitudinal study from the OSTPRE cohort. AB - BACKGROUND: Osteoporosis and depression are major health problems worldwide. The association between antidepressants, a treatment for depression, and bone health needs more detailed exploration. OBJECTIVE: The present study investigates antidepressant medication use and postmenopausal bone loss over time. METHODS: A total of 1988 women (aged 57-67) participating in the Kuopio Osteoporosis Risk Factor and Prevention Study (OSTPRE) cohort responded to a postal enquiry and had their femoral neck bone mineral density (BMD) measured in 1999 and again in 2004. Data on antidepressant use was obtained from the National Prescription Register. Multiple regression techniques were used to test the associations, before and after adjustment for anthropometric, medical, physical and lifestyle factors. RESULTS: Over the five years of follow-up, 319 (16.0%) women purchased antidepressants. Mean baseline femoral neck BMD for the entire study group was 881mg/cm(2) (SD 123) and mean 5-year bone loss was 6.0mg/cm(2) (SD 4.7). After adjustments, users of tricyclic antidepressants (TCA) had greater annual BMD loss than non-users (-3.6mg/cm(2) vs. -1.1mg/cm(2); P=0.031). Accelerated bone loss was also associated with selective serotonin reuptake inhibitor's (SSRI) use (P=0.001) and use of other antidepressants in a dose-response way, with the latter only among women of low-weight and normal-weight women who had lost weight over the study period. CONCLUSIONS: In conclusion, the use of SSRIs seems to accelerate postmenopausal bone loss in a dose-response manner. Associations between TCA and other antidepressant use and bone loss may also exist. Thus, the possibility of increased risk of osteoporosis should be considered when prescribing antidepressants for postmenopausal women. PMID- 27179632 TI - Can preoperative thyroglobulin antibody levels be used as a marker for well differentiated thyroid cancer? AB - BACKGROUND: It has been reported that thyroglobulin antibody are more frequently elevated in patients with thyroid cancercompared to general population. This study aims at evaluating whether preoperative thyroglobulin antibody (TgAb) levels increase the likelihood that a thyroid nodule is malignant. METHODS: A retrospective review of 586 patients who underwent thyroidectomy was conducted. Demographic data, TgAb levels, and final histopathology were recorded. Patients were divided into two groups: TgAb positive (defined as TgAb >= 30 IU/ml) and TgAb low/negative (defined as TgAb < 30). RESULTS: Preoperative TgAb levels were available in 405 patients. There were 353 (87 %) patients in the TgAblow/negative group (malignancy rate: 50.42 %) and 52 (13 %) patients in the TgAb positive group (malignancy rate: 65.38 %). The sensitivity, specificity, positive predictive value and negative predictive value of TgAb >= 30 IU/ml for thyroid malignancy were 16.04 %, 90.67 %, 65.38 % and 49.58 %, respectively. The relative risk of having a malignant thyroid nodule when the TgAb titers were>=30 IU/ml was 1.30 (CI1.04-1.62) and the odds ratio was 1.86 (CI 1.01-3.41). Both the Pearson chi-square test (p = 0.024) and Fisher's exact test (p = 0.017) yielded statistical significance between the two groups. CONCLUSIONS: In this study, patients with preoperative TgAb >= 30 IU/ml had a higher rate of malignancy when compared topatients with TgAb < 30 IU/ml. This suggests that an elevated TgAb level may indicate that a thyroid nodule is at an increased risk for malignancy. PMID- 27179633 TI - CD24 cell surface expression in Mvt1 mammary cancer cells serves as a biomarker for sensitivity to anti-IGF1R therapy. AB - BACKGROUND: The pro-tumorigenic effects of the insulin-like growth factor receptor (IGF1R) are well described. IGF1R promotes cancer cell survival and proliferation and prevents apoptosis, and, additionally it was shown that IGF1R levels are significantly elevated in most common human malignancies including breast cancer. However, results from phase 3 clinical trials in unselected patients demonstrated lack of efficacy for anti-IGF1R therapy. These findings suggest that predictive biomarkers are greatly warranted in order to identify patients that will benefit from anti-IGF1R therapeutic strategies. METHODS: Using the delivery of shRNA vectors into the Mvt1 cell line, we tested the role of the IGF1R in the development of mammary tumors. Based on CD24 cell surface expression, control and IGF1R-knockdown (IGF1R-KD) cells were FACS sorted into CD24(-) and CD24(+) subsets and further characterized in vitro. The tumorigenic capacity of each was determined following orthotopic inoculation into the mammary fat pad of female mice. Tumor cells were FACS characterized upon sacrifice to determine IGF1R effect on the plasticity of this cell's phenotype. Metastatic capacity of the cells was assessed using the tail vein assay. RESULTS: In this study we demonstrate that downregulation of the IGF1R specifically in cancer cells expressing CD24 on the cell surface membrane affect both their morphology (from mesenchymal-like into epithelial-like morphology) and phenotype in vitro. Moreover, we demonstrate that IGF1R-KD abolished both CD24(+) cells capacity to form mammary tumors and lung metastatic lesions. We found in both cells and tumors a marked upregulation in CTFG and a significant reduction of SLP1 expression in the CD24(+)/IGF1R-KD; tumor-suppressor and tumor-promoting genes respectively. Moreover, we demonstrate here that the IGF1R is essential for the maintenance of stem/progenitor-like cancer cells and we further demonstrate that IGF1R-KD induces in vivo differentiation of the CD24(+) cells toward the CD24(-) phenotype. This further supports the antitumorigenic effects of IGF1R-KD, as we recently published that these differentiated cells demonstrate significantly lower tumorigenic capacity compared with their CD24(+) counterparts. CONCLUSIONS: Taken together these findings suggest that CD24 cell surface expression may serve as a valuable biomarker in order to identify mammary tumors that will positively respond to targeted IGF1R therapies. PMID- 27179634 TI - Time-programmed release of fluoroscein isocyanate dextran from micro-pattern designed polymer scrolls. AB - In this article we present a relevant strategy for a non-trivial time-programmed release of water-soluble macromolecules from biocompatible MU-containers. The system is based on self-scrolled chitosan acetate (CA) fibers, encapsulated in a poly(dimethylsiloxane) matrix. Mass transfer between a fiber and the external environment takes place via the only opened extremity of the fiber. Fluoroscein isocyanate dextran (FID) is initially deposited at the inner surface of the CA fiber according to a programmed pattern. The FID molecules became mobile after the arriving of the swelling front, which propagates along the fiber's axis upon the immersion of the system in aqueous solution. Diffusion of the macromolecules into the environment is enabled by the open-tube geometry of the swollen part of the fiber, while a programmed kinetics of the drug release is due to patterning of the polymer film prior to rolling. The release of the macromolecules can be retarded by a few hours according to the placement of the FID spot with respect to the fibers orifice. A pulsatile release kinetics is demonstrated for a discrete pattern. A few millimeter spacing of the FID spots results in a few hours time interval between the release impulses. Random walk model is plugged in the effective diffusion coefficient for Fick's law and the release kinetics are simulated. PMID- 27179636 TI - Stunned myocardium after an anesthetic procedure in a pediatric patient - case report. AB - Takotsubo syndrome (TTS) is an acquired transient type of systolic dysfunction which mimics myocardial infarction clinically and electrocardiographically. TTS is also known as stress cardiomyopathy, broken heart syndrome, apical ballooning, reversible acute heart failure, neurogenic stunned myocardium or acute catecholamine cardiomyopathy. This case report describes an uncommon presentation of myocardial stunning after an anesthetic procedure. A 14-year-old girl with a history of pineal cyst and hemiplegic migraine was admitted for control brain magnetic resonance imaging. During anesthesia induction with propofol she suffered bradycardia, which was reversed with atropine, followed by tachyarrhythmia, reversed with lidocaine and precordial thump. Within hours she developed pulmonary edema and global respiratory failure due to acute left ventricular dysfunction. A transthoracic echocardiogram showed a dilated left ventricle with global hypokinesia and depressed left ventricular systolic function (ejection fraction <30%). The electrocardiogram showed persistent sinus tachycardia and nonspecific ST-T wave abnormalities. Cardiac biomarkers were elevated (troponin 2.42 ng/ml, proBNP 8248 pg/ml). She was placed on diuretics, angiotensin-converting enzyme inhibitors, digoxin and dopamine. The clinical course was satisfactory with clinical, biochemical and echocardiographic improvement within four days. Subsequent echocardiograms showed no ventricular dysfunction. The patient was discharged home on carvedilol, which was discontinued after normalization of cardiac function on cardiac magnetic resonance imaging. Few cases of TTS have been described in children, some of them triggered by acute central nervous system disorders and others not fulfilling all the classical diagnostic criteria. In this case the anesthetic procedure probably triggered the TTS. PMID- 27179637 TI - Left ventricular pseudoaneurysm - a challenging diagnosis. AB - Left ventricular pseudoaneurysm is a rare complication of acute myocardial infarction, associated with high mortality. However, it can present in a non specific manner, complicating and delaying the diagnosis. The authors present the case of a 65-year-old patient, hypertensive, with no other known relevant medical history, who presented with chest pain, cough and left pleural effusion, initially attributed to a pulmonary process. However, these were in fact the result of a left ventricular pseudoaneurysm following silent acute myocardial infarction. The diagnosis was suspected on echocardiography and confirmed by cardiac magnetic resonance imaging, and the patient underwent successful surgical pseudoaneurysm repair. This case illustrates an atypical presentation of a left ventricular pseudoaneurysm, in which the manifestations resulted from pericardial and pleural extension of the inflammatory process associated with contained myocardial rupture. The case demonstrates the need for a high index of suspicion, and the value of imaging techniques to confirm it, in order to proceed with appropriate surgical treatment, and thus modify the course of the disease. PMID- 27179638 TI - The mechanisms underlying the beneficial effects of exercise on bone remodeling: Roles of bone-derived cytokines and microRNAs. AB - Bone remodeling is highly dynamic and complex in response to mechanical loading, such as exercise. In this review, we concluded that a number of individual factors are disturbing the clinical effects of exercise on bone remodeling. We updated the progress made on the differentiation of osteoblasts and osteoclasts in response to mechanical loading, hoping to provide a theoretical basis to improve bone metabolism with exercise. Increasing evidences indicate that bone is not only a structural scaffold but also an endocrine organ, which secretes osteocalcin and FGF23. Both of them have been known as a circulating hormone to promote insulin sensitivity and reduce body fat mass. The effects of exercise on these bone-derived cytokines provide a better understanding of how exercise induced "osteokine" affects the whole-body homeostasis. Additionally, we discussed recent studies highlighting the post-transcriptional regulation of microRNAs in bone remodeling. We focus on the involvement of the microRNAs in osteoblastogenesis and osteoclastogenesis, and suggest that microRNAs may be critical for exercise-induced bone remodeling. PMID- 27179635 TI - Periadventitial drug delivery for the prevention of intimal hyperplasia following open surgery. AB - BACKGROUND: Intimal hyperplasia (IH) remains a major cause of poor patient outcomes after surgical revascularization to treat atherosclerosis. A multitude of drugs have been shown to prevent the development of IH. Moreover, endovascular drug delivery following angioplasty and stenting has been achieved with a marked diminution in the incidence of restenosis. Despite advances in endovascular drug delivery, there is currently no clinically available method of periadventitial drug delivery suitable for open vascular reconstructions. Herein we provide an overview of the recent literature regarding innovative polymer platforms for periadventitial drug delivery in preclinical models of IH as well as insights about barriers to clinical translation. METHODS: A comprehensive PubMed search confined to the past 15years was performed for studies of periadventitial drug delivery. Additional searches were performed for relevant clinical trials, patents, meeting abstracts, and awards of NIH funding. RESULTS: Most of the research involving direct periadventitial delivery without a drug carrier was published prior to 2000. Over the past 15years there have been a surge of reports utilizing periadventitial drug-releasing polymer platforms, most commonly bioresorbable hydrogels and wraps. These methods proved to be effective for the inhibition of IH in various animal models (e.g. balloon angioplasty, wire injury, and vein graft), but very few have advanced to clinical trials. There are a number of barriers that may account for this lack of translation. Promising new approaches including the use of nanoparticles will be described. CONCLUSIONS: No periadventitial drug delivery system has reached clinical application. For periadventitial delivery, polymer hydrogels, wraps, and nanoparticles exhibit overlapping and complementary properties. The ideal periadventitial delivery platform would allow for sustained drug release yet exert minimal mechanical and inflammatory stresses to the vessel wall. A clinically applicable strategy for periadventitial drug delivery would benefit thousands of patients undergoing open vascular reconstruction each year. PMID- 27179639 TI - Disturbed MEK/ERK signaling increases osteoclast activity via the Hedgehog-Gli pathway in postmenopausal osteoporosis. AB - Postmenopausal osteoporosis is a worldwide health problem and is characterized by increased and activated osteoclasts. However, the mechanism by which osteoclasts are dysregulated in postmenopausal osteoporosis is not fully understood. In this study, we found that the Hedgehog-Gli pathway was upregulated in postmenopausal osteoporotic osteoclasts and that 17beta-estradiol both inhibited osteoclastogenesis and induced osteoclast apoptosis by downregulating Hedgehog Gli signaling. Furthermore, we demonstrated that the Hedgehog-Gli pathway was negatively regulated by MEK/ERK signaling and that this effect was Sonic Hedgehog (SHH)-dependent and was partially blocked by an anti-SHH antibody. Moreover, we found that the stimulatory effect of Hedgehog signaling on osteoclastogenesis and the inhibitory effect on osteoclast apoptosis were dependent on the Gli family of transcription factors. The pathways and molecules that contribute to the regulation of osteoclastogenesis and apoptosis represent potential new strategies for designing molecular drugs for the treatment of postmenopausal osteoporosis. PMID- 27179640 TI - On the microscopic and mesoscopic perturbations of lipid bilayers upon interaction with the MPER domain of the HIV glycoprotein gp41. AB - The effect of the 665-683 fragment of the HIV fusion glycoprotein 41, corresponding to the MPER domain of the protein and named gp41MPER, on the microscopic structure and mesoscopic arrangement of palmitoyl oleoyl phosphatidylcholine (POPC) and POPC/sphingomyelin (SM)/cholesterol (CHOL) lipid bilayers is analyzed. The microscopic structuring of the bilayers has been studied by Electron Spin Resonance (ESR) spectroscopy, using glycerophosphocholines spin-labelled in different positions along the acyl chain. Transitions of the bilayer liquid crystalline state have been also monitored by Differential Scanning Calorimetry (DSC). Changes of the bilayers morphology have been studied by determining the dimension of the liposomes through Dynamic Light Scattering (DLS) measurements. The results converge in showing that the sample preparation procedure, the bilayer composition and the peptide/lipid ratio critically tune the lipid response to the peptide/membrane interaction. When gp41MPER is added to preformed liposomes, it positions at the bilayer interface and the lipid perturbation is limited to the more external segments. In contrast, if the peptide is mixed with the lipids during the liposome preparation, it assumes a trans-membrane topology. This happens at all peptide/lipid ratios for fluid POPC bilayers, while in the case of rigid POPC/SM/CHOL membranes a minimum ratio has to be reached, thus suggesting peptide self-aggregation to occur. Peptide insertion results in a dramatic increase of the lipid ordering and bilayer stiffening, which reflect in significant changes in liposome average dimension and distribution. The biological implications of these findings are discussed. PMID- 27179641 TI - Protein architecture and core residues in unwound alpha-helices provide insights to the transport function of plant AtCHX17. AB - Using Arabidopsis thaliana AtCHX17 as an example, we combine structural modeling and mutagenesis to provide insights on its protein architecture and transport function which is poorly characterized. This approach is based on the observation that protein structures are significantly more conserved in evolution than linear sequences, and mechanistic similarities among diverse transporters are emerging. Two homology models of AtCHX17 were obtained that show a protein fold similar to known structures of bacterial Na(+)/H(+) antiporters, EcNhaA and TtNapA. The distinct secondary and tertiary structure models highlighted residues at positions potentially important for CHX17 activity. Mutagenesis showed that asparagine-N200 and aspartate-D201 inside transmembrane5 (TM5), and lysine-K355 inside TM10 are critical for AtCHX17 activity. We reveal previously unrecognized threonine-T170 and lysine-K383 as key residues at unwound regions in the middle of TM4 and TM11 alpha-helices, respectively. Mutation of glutamate-E111 located near the membrane surface inhibited AtCHX17 activity, suggesting a role in pH sensing. The long carboxylic tail of unknown purpose has an alternating beta sheet and alpha-helix secondary structure that is conserved in prokaryote universal stress proteins. These results support the overall architecture of AtCHX17 and identify D201, N200 and novel residues T170 and K383 at the functional core which likely participates in ion recognition, coordination and/or translocation, similar to characterized cation/H(+) exchangers. The core of AtCHX17 models according to EcNhaA and TtNapA templates faces inward and outward, respectively, which may reflect two conformational states of the alternating access transport mode for proteins belonging to the plant CHX family. PMID- 27179642 TI - Stability-indicating UHPLC method for determination of nevirapine in its bulk form and tablets: identification of impurities and degradation kinetic study. AB - Nevirapine (NVP), a non-nucleoside reverse transcriptase inhibitor, is a drug widely used in the treatment of Acquired Immunodeficiency Syndrome (AIDS). The evaluation of NVP stability is of fundamental importance in order to guarantee drug product efficacy, safety and quality. In this study, NVP active pharmaceutical ingredient (API) and tablets were subjected to a detailed study of forced degradation, employing several degrading agents (acid, alkaline, water, metal ions, humidity, heat, light and oxidation agents). In order to determine NVP and the degradation products formed, a stability-indicating UHPLC method using fused core column was developed and validated. The separation was carried out using a Poroshell 120C18 column (100*2.1mm i.d.; 2.7MUm particle size) and the mobile phase was composed of acetonitrile and water in a gradient elution, at a flow rate of 0.2ml/min. Chemical structures and mechanisms for the formation of three degradation products were proposed by means of LC/MS-MS. Also, NVP degradation kinetic was studied and its order of degradation evaluated. NVP was degraded in acidic and oxidative conditions and the degradation profile for NVP tablets and API were similar. The stability-indicating method proved to be selective for NVP and its degradation products. Calibration curve was linear in the range of 8-48MUg/ml and the method showed to be precise, accurate and robust for both NVP API and tablets, with detection and quantification limits of 0.092MUg/ml and 0.174MUg/ml, respectively. PMID- 27179643 TI - Tracking activity and function of microorganisms by stable isotope probing of membrane lipids. AB - Microorganisms in soils and sediments are highly abundant and phylogenetically diverse, but their specific metabolic activity and function in the environment is often not well constrained. To address this critical aspect in environmental biogeochemistry, different methods involving stable isotope probing (SIP) and detection of the isotope label in a variety of molecular compounds have been developed. Here we review recent progress in lipid-SIP, a technique that combines the assimilation of specific 13C-labeled metabolic substrates such as inorganic carbon, methane, glucose and amino acids into diagnostic membrane lipid compounds. Using the structural characteristics of certain lipid types in combination with genetic molecular techniques, the SIP approach reveals the activity and function of distinct microbial groups in the environment. More recently, deuterium labeling in the form of deuterated water (D2O) extended the lipid-SIP portfolio. Since lipid biosynthetic pathways involve hydrogen (H+) uptake from water, lipid production can be inferred from the detection of D assimilation into these compounds. Furthermore, by combining D2O and 13C inorganic carbon (IC) labeling in a dual-SIP approach, rates of auto- and heterotrophic carbon fixation can be estimated. We discuss the design, analytical prerequisites, data processing and interpretation of single and dual-SIP experiments and highlight a case study on anaerobic methanotrophic communities inhabiting hydrothermally heated marine sediments. PMID- 27179644 TI - Cell confluency analysis on microcarriers by micro-flow imaging. AB - The productivity of cell culture-derived vaccines grown in anchorage-dependent animal cells is limited by bioreactor surface area. One way to increase the available surface area is by growing cells as monolayers on small spheres called microcarriers, which are approximately 100-250 MUm in diameter. In order for microcarrier-based cell culture to be a success, it is important to understand the kinetics of cell growth on the microcarriers. Micro-flow imaging (MFI) is a simple and powerful technique that captures images and analyzes samples as they are drawn through a precision flow cell. In addition to providing size distribution and defect frequency data to compare microcarrier lots, MFI was used to generate hundreds of images to determine cell coverage and confluency on microcarriers. Same-day manual classification of these images provided upstream cell culture teams with actionable data that informed in-process decision making (e.g. time of infection). Additionally, an automated cell coverage algorithm was developed to increase the speed and throughput of the analyses. PMID- 27179645 TI - Three homicides with darts tainted with succinylcholine: autopsy and toxicology. AB - In emergency departments, intoxication with the muscle relaxant succinylcholine (SUX) often leads to a potentially lethal respiratory paralysis or other deleterious side effects. However, homicide cases with SUX poisoning are very rare because the toxic or lethal concentration ranges of SUX have not yet been determined. We described three uncommon homicide cases due to acute poisoning by darts contaminated with SUX. All the victims died quickly (less than 30 min) after being shot by an especially designed dart gun. Succinylmonocholine (SMC), a metabolite of SUX, was used as a marker to detect the latter. HPLC-MS/MS analysis demonstrated the presence of SUX in the droplet residues of the darts and SMC in the blood and urine in all cases. SMC concentrations of 0.45, 14.0, and 17.9 ng/ml were detected in the victims' blood and 259.0 ng/ml in the urine from the third case. The main pathological changes consisted of hemorrhage of the injured soft tissues, visceral congestion, severe pulmonary edema, and multifocal petechial hemorrhage of the heart and lungs. Taken together, the findings supported a diagnosis of fatal SUX poisoning. Futhermore, our study provided a reference for the lethal concentrations of SUX poisoning. PMID- 27179647 TI - Journal of Echocardiography Award for the Year 2015. PMID- 27179648 TI - Koch's postulates, microbial dysbiosis and inflammatory bowel disease. AB - Over the past 20 years, a growing amount of evidence supports the role of microbes and an imbalanced microbiota in inflammatory bowel disease (IBD). While many reviews have been written on the microbiota in IBD, few have considered how they fulfil the Koch's postulates. In this review, we consider how the Koch's postulates might be modified so that they can be fulfilled for polymicrobial diseases, and we discuss the progress made to date in fulfilling them. PMID- 27179646 TI - The detection of gunshot residues in the nasal mucus of suspected shooters. AB - The identification and quantification of metallic residues produced by gunshots, called gunshot residues (GSR), provide crucial elements in forensic investigations. The research has been largely focused on their collection onto the hands of suspected shooters, but the method is often burdened by risks of contamination. This research was focused on the possibility of sampling GSR trapped inside the nasal mucus of consenting shooters. Samples of the nasal mucus of "blank" control subjects and shooters were chemically analysed by Instrumental Neutron Activation Analysis (INAA), for residues of antimony (Sb) and barium (Ba), while lead (Pb) was excluded as ubiquitously environmental contaminant and due to high instrumental quantification limit (IQL) of INAA for this element. Shots were fired using two types of weapons (pistols and revolvers) and different firing sequences. The mucus was sampled at different times: immediately after the shots, after 30-60-120 and 180 min. Different amounts of Sb and Ba were detected between controls and shooters, witnessing the ability of the nasal mucus to retain GSR at concentrations significantly different even from the highest basal levels. Moreover, in order to simulate actual cases, nasal mucus from five groups of shooters was sampled after different shots with the same weapon and cartridges, immediately and after 1, 3, 12, and 24 h. The highest values were always found in the first 3 h from firing, for both weapons. Interestingly, for all the weapons, significant Sb and Ba concentrations were also found up to 12 h after firing, contrary to what occurs on hands, even though a progressive decrease was detected, with values below the detection threshold only after 24 h, thus demonstrating that GSR are persistent in nasal mucus. These first results proving that both Sb and Ba were qualitatively detectable in the nasal mucus of shooters indicate that the chemical analysis of the nasal mucus of suspected shooters may represent a promising tool in the forensic field since it is less burdened by problems related to sampling or contamination than the usual sampling on hand, providing that ammunitions employed contain Ba and Sb. PMID- 27179649 TI - Accidental blood exposures among emergency medicine residents and young physicians in France: a national survey. AB - The aim of the present study was to investigate the epidemiological characteristics of blood or fluid exposure (BFE) and occupational infection risk among emergency medicine (EM) residents and young physicians (<35 years old) in France. We led a cross-sectional, anonymous, online survey. 1779 participants were contacted with a response rate of 36 % (n = 633). Among the respondents, 459 (72 %) reported at least one BFE. Among participants with at least one BFE, 35 % (n = 163) never reported the exposure to the relevant medical authorities or support. Among participants who reported exposure, 63 % (n = 232) did it immediately. Among participants who never or not systematically reported their BFE, most of them (62 %, n = 181/289) did not do so because the procedure was too long, and 28 % (n = 82/289) estimated the risk as low even if only one-third (n = 166/458) checked their HIV status even though the BFE was at a transmission risk. Circumstances in which the participants had the most BFE were: suturing 57 % (n = 262/457) and when making precipitated gestures 24 % (n = 111/457). The latest exposures were caused by a solid needle in 42 % (n = 191/455) or hollow-bore needle in 27 % (n = 123/455). Post-exposure reporting rates were low. Reporting procedure itself and self-management were the main reasons for BFE underreporting. Simplifying procedures might increase BFE reporting, and allow appropriate post-exposure counseling and/or prophylaxis. PMID- 27179650 TI - Utilization of chemical shift MRI in the diagnosis of disorders affecting pediatric bone marrow. AB - OBJECTIVE: MRI signal intensity of pediatric bone marrow can be difficult to interpret using conventional methods. Chemical shift imaging (CSI), which can quantitatively assess relative fat content, may improve the ability to accurately diagnose bone marrow abnormalities in children. METHODS: Consecutive pelvis and extremity MRI at a children's hospital over three months were retrospectively reviewed for inclusion of CSI. Medical records were reviewed for final pathological and/or clinical diagnosis. Cases were classified as normal or abnormal, and if abnormal, subclassified as marrow-replacing or non-marrow replacing entities. Regions of interest (ROI) were then drawn on corresponding in and out-of-phase sequences over the marrow abnormality or over a metaphysis and epiphysis in normal studies. Relative signal intensity ratio for each case was then calculated to determine the degree of fat content in the ROI. RESULTS: In all, 241 MRI were reviewed and 105 met inclusion criteria. Of these, 61 had normal marrow, 37 had non-marrow-replacing entities (osteomyelitis without abscess n = 17, trauma n = 9, bone infarction n = 8, inflammatory arthropathy n = 3), and 7 had marrow-replacing entities (malignant neoplasm n = 4, bone cyst n = 1, fibrous dysplasia n = 1, and Langerhans cell histiocytosis n = 1). RSIR averages were: normal metaphyseal marrow 0.442 (0.352-0.533), normal epiphyseal marrow 0.632 (0.566-698), non-marrow-replacing diagnoses 0.715 (0.630-0.799), and marrow-replacing diagnoses 1.06 (0.867-1.26). RSIR for marrow-replacing entities proved significantly different from all other groups (p < 0.05). ROC analysis demonstrated an AUC of 0.89 for RSIR in distinguishing marrow-replacing entities. CONCLUSION: CSI techniques can help to differentiate pathologic processes that replace marrow in children from those that do not. PMID- 27179651 TI - Assessment of trunk muscle density using CT and its association with degenerative disc and facet joint disease of the lumbar spine. AB - OBJECTIVE: The purpose of this study was (1) to evaluate the association of trunk muscle density assessed by computed tomography (CT) with age, gender, and BMI and (2) to evaluate the association between trunk muscle CT density and degenerative disc and facet joint disease of the lumbar spine. MATERIAL AND METHODS: The study was IRB approved and HIPAA compliant. The study group comprised 100 subjects (mean age 44.4 +/- 22.2 years, 51 % male) who underwent CT of the abdomen and pelvis without intravenous contrast. Exclusion criteria included prior abdominal or spine surgery, active malignancy and scoliosis. CTs were reviewed and the attenuation of the rectus abdominis, transverse abdominis, internal and external obliques, psoas, multifidus, longissimus and gluteus maximus were measured bilaterally at consistent levels. Degenerative disc and bilateral facet joint disease were scored using established methods. Univariate analyses were performed using linear regression. Multivariate linear regression was performed to adjust for age, gender and BMI. RESULTS: CT density of each trunk muscle correlated inversely with age (p < 0.001) and BMI (p < 0.001). CT density of each trunk muscle correlated inversely with degenerative disc and facet joint disease in the univariate analyses (p < 0.001); however, only the gluteus maximus and the transverse abdominis remained significant predictors of degenerative disc and facet joint disease respectively in the multivariate analysis. CONCLUSION: Fatty infiltration of trunk musculature increases with age and BMI. Fatty infiltration of the gluteus maximus and transverse abdominis are associated with degenerative disc and facet joint disease, independent of age, gender and BMI. PMID- 27179652 TI - Periosteal chondroma with spinal cord compression in the thoracic spinal canal: a case report. AB - Periosteal chondroma is a very unusual cartilaginous neoplasm of the spinal canal. We herein report a case of periosteal chondroma in a 41-year-old male who presented with gait disturbance and paresthesia of both lower extremities. Magnetic resonance (MR) images showed an extradural mass which caused compression of the spinal cord at the T5/6 level. The mass showed iso-signal intensity on T1 weighted images, high signal intensity on T2-weighted images, and nodular and peripheral rim enhancement on post-contrast T1-weighted images. Computed tomography (CT) images showed a mass with punctate calcifications and extension into the left T5/6 neural foramen. MR and CT images showed extrinsic cortical bone erosion of the posterior inferior body of T5 and superior pedicle of T6, bone remodeling with overhanging margins, and sclerosis adjacent to the tumor. The patient underwent a complete excision of the mass by left T5/6 hemi laminectomy and exhibited complete resolution of his symptoms. Histopathologic examination revealed periosteal chondroma. Tumor recurrence was not recorded during the 18-month follow-up period. PMID- 27179654 TI - Prevalence of inter-appointment endodontic flare-ups and host-related factors. AB - OBJECTIVES: The aims of this study were to report the prevalence of inter appointment flare-ups following adequate root canal disinfection and to investigate the host factors contributing to its occurrence. MATERIALS AND METHODS: One thousand five hundred patient records were reviewed and the prevalence of flare-up was recorded. Patients' root canal space status (vital, non-vital or retreatment), medical condition and demographics (age, gender, tooth type and position) were recorded from their dental records. Statistical analyses were performed to determine the impact of the recorded factors on flare-up occurrence. RESULTS: Nine hundred fifty-one patient records met the inclusion criteria. The prevalence of flare-up was 2.3 %. There was a correlation between the canal space status and patient's age with flare-up development (P < 0.05). There was no association between flare-up occurrence and tooth type, location, gender or medical condition (P > 0.5). CONCLUSION: The root canal space status was the primary factor affecting flare-up occurrence. Patients >50 years had the highest risk in developing flare-ups. CLINICAL RELEVANCE: This article provides evidence that patients suffering from inflamed pulp will not develop flare-up if adequate cleaning and shaping of the root canal space was performed. It also shows that patients above the age of 50 are a high-risk group that is prone to flare-up development. PMID- 27179653 TI - In vitro evaluation of different dental materials used for the treatment of extensive cervical root defects using human periodontal cells. AB - INTRODUCTION: Repair materials for extensive cervical root defects may come in direct contact with periodontal tissues. This in vitro study compared the effects of four calcium silicate cements (CSC), one resin-modified glass ionomer cement, and one glass carbomer cement on primary human gingival fibroblasts (HGF), alveolar osteoblasts (HAO), and a human osteoblast cell line (hFOB 1.19). METHODS: HGF, HAO, and hFOB were seeded on discoid test specimens. Relative numbers of viable cells were quantitatively assessed after 1 and 24 h for cytotoxicity/adhesion assays and after 4, 24, 48, and 72 h for proliferation assays. Data were statistically analyzed using non-parametric tests (alpha = 0.05). RESULTS: Relative to the control (100 %), CSC allowed for mean numbers of 71-81 % viable HGF and 80-82 % viable HAO. Then, 64 % of HGF and 56 % of HAO were assessed on GC Fuji II LC. Mean numbers of viable cells were 59-64 % HGF and 67 68 % HAO for GCP Glass Fill specimens. Cells exposed to CSC over 24 h remained viable and even increased in number. Both cell types adhered almost equally well to CSC and GC Fuji II LC. GCP Glass Fill continued to decrease cell viability and adhesion. CSC-based materials and GC Fuji II LC allowed for HGF and hFOB proliferation; however, none of the tested materials specifically stimulated cell proliferation. CONCLUSIONS: CSC characterized by low cytotoxicity. GC Fuji II LC shows moderate cytotoxic effects. ProRoot MTA, Harvard MTA, Biodentine, EndoSequence putty, and GC Fuji II LC allow HGF and HAO to adhere and HGF and hFOB to proliferate. GCP Glass Fill decreases cell viability, adhesion, and proliferation. CLINICAL RELEVANCE: CSC remain the paramount biologic choice for the repair of extensive cervical root defects. GC Fuji II LC might be considered in addition to CSC when the defect comprises supracrestal areas and the restoration requires superior aesthetic and mechanical characteristics. PMID- 27179655 TI - Worsening of lipid metabolism after successful treatment of primary aldosteronism. AB - Primary aldosteronism (PA) describes the most frequent cause of secondary arterial hypertension. Recently, deterioration of lipid metabolism after adrenalectomy (ADX) for aldosterone-producing adenoma (APA) has been described. We analysed longitudinal changes in lipid profiles in a large prospective cohort of PA patients. Data of 215 consecutive PA patients with APA (n = 144) or bilateral idiopathic adrenal hyperplasia (IHA, n = 71) were extracted from the database of the German Conn's Registry. Patients were investigated before and 1 year after successful treatment by ADX or by mineralocorticoid receptor antagonists (MRA). Glomerular filtration rate (GFR), fasting plasma glucose and components of lipid metabolism including triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were determined at 8.00 after a 12-h fasting period. One year after initiation of treatment mean serum potassium levels and blood pressure normalized in the patients. HDL-C and TG developed inversely with decreasing HDL C levels in patients with APA (p = .046) and IHA (p = .004) and increasing TG levels (APA p = .000; IHA p = .020). BMI remained unchanged and fasting plasma glucose improved in patients with APA (p = .004). Furthermore, there was a significant decrease of GFR in both subgroups at follow-up (p = .000). Changes in HDL-C and TG correlated with decrease in GFR in multivariate analysis (p = .024). Treatment of PA is associated with a deterioration of lipid parameters despite stable BMI and improved fasting plasma glucose and blood pressure. This effect can be explained by renal dysfunction following ADX or MRA therapy. PMID- 27179656 TI - Inhibition of BRAF kinase suppresses cellular proliferation, but not enough for complete growth arrest in BRAF V600E mutated papillary and undifferentiated thyroid carcinomas. AB - The aim of our study was to inhibit BRAF kinase expression and investigate its effect on cellular functions in thyroid carcinomas. 8505C (BRAF V600E/V600E) undifferentiated thyroid carcinoma cell line and B-CPAP (BRAF V600E/V600E) papillary thyroid carcinoma cell line were used to develop doxycycline-inducible anti-BRAF shRNA stable cell lines. The inhibitions of BRAF expression in these cells were confirmed with qPCR and Western blot. Impacts of BRAF protein inhibition on cellular functions and signalling pathways were observed through Western blot, proliferation and colony formation assays. BRAF kinase expression was inhibited 83 % in undifferentiated thyroid carcinoma and 82 % in papillary thyroid carcinoma (p < 0.05). As a result of BRAF kinase inhibition, reduction in MEK kinase activity was seen (p < 0.05) in both thyroid cancer cell lines (72 and 75 %, respectively). Initially, big drop in proliferation (p < 0.05) was observed (52 and 54 %, respectively), but later an increasing proliferation trend was noticed in BRAF kinase-inhibited cell lines. In addition, reduction in colony formation (p < 0.05) was seen in BRAF kinase-inhibited carcinoma cells (13 and 15 %, respectively). On the other hand, increase in AKT kinase activity (63 and 70 %, respectively; p < 0.05) was discovered in both BRAF kinase-inhibited carcinoma cells. Increased activation of alternative proliferation pathways (as determined by the increase of AKT kinase activity) counteracts the effect of BRAF kinase inhibition in thyroid carcinomas. Thus, alternative proliferation pathways should be inhibited for therapeutic suppression of BRAF-induced proliferation in thyroid carcinomas. PMID- 27179657 TI - Left ventricular geometry and 24-h blood pressure profile in Cushing's syndrome. AB - Cushing's syndrome (CS) is associated with cardiovascular disease. The impact of the hemodynamic load on left ventricular mass (LVM) in patients with CS is not well known. In fact, the effects of 24-h blood pressure (BP) load and BP circadian rhythm on cardiac structure and function have not been studied. Aim of the present study has thus been to assess the presence of cardiac remodeling in patients with newly diagnosed CS, combining evaluation of cardiac remodeling and assessment of BP burden derived by 24-h ambulatory blood pressure monitoring (ABPM). 25 patients (4 M, 21 F) with CS underwent echocardiography in order to assess cardiac morphology and geometry (relative wall thickness-RWT). As controls, 25 subjects similar for demographic characteristics and 24-h BP were used. CS Patients were similar to controls by age, sex, mean 24-h BP, and body mass index. There was a significant increase in left ventricular mass (LVM; 44.4 +/- 14.7 vs. 36.9 +/- 10 g/m2.7, p = 0.03) and a significant increase in RWT (0.46 +/- 0.07 vs. 0.41 +/- 0.08, p = 0.02) in CS patients compared to controls. The prevalence of CS patients with pressure non-dipping profile was greater than that of controls (56 vs. 16 %, p < 0.05), with no significant association with LVM or geometry. 24-h urinary cortisol was not associated with LVM (r = 0.1, p = 0.5) or RWT (r = 0.02, p = 0.89) in the CS group. In conclusion, LVM and the concentric pattern of the left ventricle are relatively independent from 24-h BP load and profile (dipping/non-dipping) in CS patients. PMID- 27179658 TI - Morphology of the pancreas in type 2 diabetes: effect of weight loss with or without normalisation of insulin secretory capacity. AB - AIMS/HYPOTHESIS: This study was designed to establish whether the low volume and irregular border of the pancreas in type 2 diabetes would be normalised after reversal of diabetes. METHODS: A total of 29 individuals with type 2 diabetes undertook a very low energy (very low calorie) diet for 8 weeks followed by weight maintenance for 6 months. Methods were established to quantify the pancreas volume and degree of irregularity of the pancreas border. Three dimensional volume-rendering and fractal dimension (FD) analysis of the MRI acquired images were employed, as was three-point Dixon imaging to quantify the fat content. RESULTS: There was no change in pancreas volume 6 months after reversal of diabetes compared with baseline (52.0 +/- 4.9 cm(3) and 51.4 +/- 4.5 cm(3), respectively; p = 0.69), nor was any volumetric change observed in the non responders. There was an inverse relationship between the volume and fat content of the pancreas in the total study population (r =-0.50, p = 0.006). Reversal of diabetes was associated with an increase in irregularity of the pancreas borders between baseline and 8 weeks (FD 1.143 +/- 0.013 and 1.169 +/- 0.006, respectively; p = 0.05), followed by a decrease at 6 months (1.130 +/- 0.012, p = 0.006). On the other hand, no changes in FD were seen in the non-reversed group. CONCLUSIONS/INTERPRETATION: Restoration of normal insulin secretion did not increase the subnormal pancreas volume over 6 months in the study population. A significant change in irregularity of the pancreas borders occurred after acute weight loss only after reversal of diabetes. Pancreas morphology in type 2 diabetes may be prognostically important, and its relationship to change in beta cell function requires further study. PMID- 27179660 TI - Military veterans and canine assistance for post-traumatic stress disorder: A narrative review of the literature. AB - BACKGROUND: Veterans with post-traumatic stress disorder (PTSD) are a vulnerable population at high risk for depression, isolation, and suicide. A substantial body of anecdotal evidence exists supporting the use of canines as an effective adjunct treatment for this population. However, a comprehensive review of its use based on scientific literature has thus far not been conducted. METHODS: A narrative literature review was conducted to examine the current state of the science on canine assistance for veterans diagnosed with PTSD in order to synthesize current empirical knowledge on the subject. Articles were retrieved among the small body of recent literature using computerized database searches. Inclusion criteria included peer-reviewed journal publications published through October 1st, 2015. Only originally published articles that examined the outcomes of canine assistance on veterans with PTSD were examined. Additionally, each included article was specific to veterans, dogs, and, PTSD in combination rather than article that discuss the concepts separately. Exclusion criteria included symposia and conference material, dissertations, media articles, and no mention of canines as a treatment modality. 563 articles were retrieved; 6 met the criteria. When evaluating data, information and themes were extracted into an Excel table; this table was employed in the synthesis of information into manuscript form. RESULTS: The following themes were explored within the selected publications: What is Canine Assistance; Why Use Canine Assistance for PTSD in Veterans; Concerns; and Future Directions. The literature endorsed canine assistance for PTSD in veterans as a promising modality. Authors also raised concerns about lack of protocols, cost and availability barriers, and animal welfare calling for additional, rigorous research to advance its use as a treatment for veterans with PTSD. CONCLUSIONS: PTSD continues to pose significant psychological, health, and welfare challenges to veterans and the multi disciplinary providers who treat them. Analysis of this literature should expand knowledge and outline future directions for healthcare professions and improve health and wellness for veterans with PTSD through the use of canine assistance. PMID- 27179659 TI - Diabetic macular oedema: pathophysiology, management challenges and treatment resistance. AB - Diabetic macular oedema (DMO) is the leading cause of vision loss in patients living with diabetes. DMO results from hyperglycaemia-induced activation of pathways that lead to oxidative stress and release of cytokines, impairing the inner and outer blood-retinal barriers. Improved understanding of the pathophysiological mechanisms leading to DMO have led to the development of effective therapies, including vitreoretinal surgery, laser photocoagulation, intravitreal anti-vascular endothelial growth factor drugs and corticosteroids. Advances in imaging, including fluorescein angiography and optical coherence tomography, have also enhanced diagnosis and management of the condition. Despite these advances, there remain patients who do not respond completely to therapy, reflecting the complex pathophysiology of DMO. These patients may be considered treatment-resistant. In this review, we summarise the pathophysiology of DMO, as well as the available treatments and their mechanism of action. Additionally, we focus on treatment-resistant disease and review the literature on potential options for managing this complication of diabetes. PMID- 27179661 TI - Solid Platelet Rich Plasma in Corneal Surgery. AB - Solid eye platelet-rich plasma (E-PRP) concentrates platelets in a small volume of plasma which contains a high concentration of important growth factors and cell adhesion molecules. These cell adhesion molecules and growth factors occupy a major role in wound healing and enhance the physiological procedure at the site of the injury or the surgery. There are different materials used to tectonically maintain the solid clot attached at the site where treatment is necessary. Although AM may be used for this purpose, other biomaterials such a bovine pericardium or autologous fibrin membrane are at least as effective with less interdonor variations, no biological hazards, providing a better surgical alternative than the biologically so variable amniotic membrane patch. Solid platelet-rich plasma in the form obtained in ophthalmology, E-PRP, is a reliable and effective surgical coadjuvant to promote corneal wound healing in severe corneal ulcers and corneal perforations, and may be associated with other ocular surface reconstruction procedures. FUNDING: Supported in part by a grant from the Spanish Ministry of Science and Innovation, Centro para el Desarrollo Tecnologico Industrial (CDTI), CENIT: "Customized Eye Care", CeyeC (CEN-20091021). PMID- 27179662 TI - ENT-specific therapy of obstructive sleep apnoea in adults : A revised version of the previously published German S2e guideline. AB - The German Society of Otorhinolaryngology, Head and Neck Surgery recently has released the abbreviated version of its scientific guideline "ENT-specific therapy of obstructive sleep apnoea (OSA) in adults", which has been updated in 2015 and can be found online at the Association of the Scientific Medical Societies (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF). A summary of the main recommendations is provided in this revised English version. All recommendations are based on a systematic literature research of articles published up until March 2014. Literature research followed the Cochrane Handbook for Systematic Literature Research to create Guidelines published by the German Cochrane Centre. Studies were evaluated with respect to their scientific value according to the recommendations of the Oxford Centre for Evidence-based Medicine, and grades of recommendation are provided regarding each intervention. PMID- 27179663 TI - Maternal exposure to high-fat and high-fructose diet evokes hypoadiponectinemia and kidney injury in rat offspring. AB - BACKGROUND: Maternal exposure to overnutrition during fetal development contributes to metabolic and renal damage in offspring. Adiponectin plays a protective role against obesity-related renal injury. However, role of adiponectin in renal injury of offspring exposed to maternal overnutrition remains unknown. We addressed the issue. METHODS: Female Sprague-Dawley rats were fed either a standard (N) or a high-fat and high-fructose (HFF)-diet for 6 weeks before mating, and kept each diet during the gestation and lactation period. After 4 weeks postpartum, all the offspring were fed N diet, and followed by 12 weeks. Kidney weight, urinary albumin excretion, blood pressure, and blood chemistry, including adiponectin and malondialdehyde, a marker of oxidative stress, were evaluated in the offspring. RESULTS: Compared with N-offspring, serum adiponectin levels of 1-day- and 4-week-old HFF-offspring were significantly lower, the latter of which was inversely associated with malondialdehyde. Kidney weight was significantly decreased in 1-day-old HFF offspring, whereas increased in 4-week-old HFF-offspring. Urinary albumin excretion levels of HFF-offspring at 8, 12, and 16-week old were significantly higher than those of N-offspring at the same age, whose levels at 16-week old were inversely correlated with plasma adiponectin. Compared with N-offspring, HFF offspring at 16-week old exhibited glomerulosclerosis, hyperglycemia, and high mean blood pressure associated with reduced podocin and increased transforming growth factor-beta1 expression in the kidneys. CONCLUSIONS: Our present study suggests that exposure to maternal HFF-diet during fetal and early postnatal development induces hypoadiponectinemia in offspring, which might cause renal injury and metabolic derangements later in life. PMID- 27179665 TI - Gabapentin prevents behavioral changes on the amphetamine-induced animal model of schizophrenia. PMID- 27179666 TI - Childhood adversity and hippocampal and amygdala volumes in a population at familial high risk of schizophrenia. AB - BACKGROUND: There is an established link between childhood adversity (CA) and schizophrenia. Hippocampus and amygdala abnormalities pre-date onset in those at high familial risk (fHR) of schizophrenia, but it is not clear whether these alterations are associated with CA in those at elevated risk of schizophrenia. METHODS: We examined hippocampal and amygdala volumes in those at fHR who had been referred to a social worker or the Children's Panel compared to those who had not. RESULTS: The right hippocampus and left amygdala were significantly smaller in those that had been referred to social work and Children's Panel. CONCLUSIONS: Our findings suggest that CA can influence structural changes in the brain in a cohort at fHR of schizophrenia. These findings provide further evidence that while genetic factors contribute to the structural changes found in schizophrenia, environmental factors such as CA can have a lasting impact on specific brain regions. PMID- 27179664 TI - Six-month outcomes from a randomized controlled trial of minimally invasive SI joint fusion with triangular titanium implants vs conservative management. AB - PURPOSE: To compare the safety and effectiveness of minimally invasive sacroiliac joint fusion (SIJF) using triangular titanium implants vs conservative management (CM) in patients with chronic sacroiliac joint (SIJ) pain. METHODS: 103 adults with chronic SIJ pain at nine sites in four European countries were randomly assigned to and underwent either minimally invasive SIJF using triangular titanium implants (N = 52) or CM (N = 51). CM was performed according to the European guidelines for the diagnosis and management of pelvic girdle pain and consisted of optimization of medical therapy, individualized physical therapy (PT) and adequate information and reassurance as part of a multifactorial treatment. The primary outcome was the difference in change in self-rated low back pain (LBP) at 6 months. Additional endpoints included quality of life using EQ-5D-3L, disability using Oswestry Disability Index (ODI), SIJ function using active straight leg raise (ASLR) test and adverse events. NCT01741025. RESULTS: At 6 months, mean LBP improved by 43.3 points in the SIJF group and 5.7 points in the CM group (difference of 38.1 points, p < 0.0001). Mean ODI improved by 26 points in the SIJF group and 6 points in the CM group (p < 0.0001). ASLR, EQ-5D 3L, walking distance and satisfaction were statistically superior in the SIJF group. The frequency of adverse events did not differ between groups. One case of postoperative nerve impingement occurred in the surgical group. CONCLUSIONS: In patients with chronic SIJ pain, minimally invasive SIJF using triangular titanium implants was safe and more effective than CM in relieving pain, reducing disability, improving patient function and quality of life. PMID- 27179667 TI - Biodiesel from soybean promotes cell proliferation in vitro. AB - Toxicological responses of exhaust emissions of biodiesel are different due to variation in methods of generation and the tested biological models. A chemical profile was generated using ICP-MS and GC-MS for the biodiesel samples obtained in Brazil. A cytotoxicity assay and cytokine secretion experiments were evaluated in human bronchial epithelial cells (BEAS-2B). Cells were exposed to polar (acetone) and nonpolar (hexane) extracts from particles obtained from fuel exhaust: fossil diesel (B5), pure soybean biodiesel (B100), soybean biodiesel with additive (B100A) and ethanol additive (EtOH). Biodiesel and its additives exhibited higher organic and inorganic constituents on particles when compared to B5. The biodiesel extracts did not exert any toxic effect at concentrations 10, 25, 50, 75, and 100MUgmL(-1). In fact quite the opposite, a cell proliferation effect induced by the B100 and B100A extracts is reported. A small increase in concentrations of inflammatory mediators (Interleukin-6, IL-6; and Interleukin-8, IL-8) in the medium of biodiesel-treated cells was observed, however, no statistical difference was found. An interesting finding indicates that the presence of metals in the nonpolar (hexane) fraction of biodiesel fuel (B100) represses cytokine release in lung cells. This was revealed by the use of the metal chelator. Results suggest that metals associated with biodiesel's organic constituents might play a significant role in molecular mechanisms associated to cellular proliferation and immune responses. PMID- 27179669 TI - Severe ocular side effects with acetazolamide: case report. AB - CLINICAL CASE: A 44-year-old woman arrived in the emergency department complaining of decreased visual acuity (VA) in oculus uterque (OU) of 4hours onset. Signs of myopia, increased intraocular pressure (IOP) in OU, and a narrow grade II anterior chamber (AC) were observed. In the posterior segment ultrasound scan, a choroidal peripheral detachment is evident, and a lenticular thickness of 4.05mm is measured in the anterior segment of the right eye (OD) and 4.00mm in the left eye (OS). On treatment with oral with naproxen (non-steroidal anti inflammatory drug), and acetazolamide for migraine. The acetazolamide is suspended and topical treatment is started with timolol and brimonidine every 12hours, with prednisolone and ayclopentolate every 8hours. In the follow-up, a gradual reduction of myopia and lens thickness is observed, as well as anterior chamber expansion. In the last control, the patient had a sphere of -0.75 diopters (D) in OD and -0.25 D in OS. IOP was 15mmHg in OU and AC was grade III. The ultrasound showed a lens thickness of 3.59mm in OD and 3.61mm in OS. CONCLUSION: This was an iatrogenic case of acute angle closure induced by an anterior displacement of the irido-lenticular complex, secondary to the use of acetazolamide. The treatment of this condition involves suspending the drug responsible and applying topical corticosteroids, hypotensive and cycloplegic eye drops, with the aim of lowering the eye pressure and the degree of myopia due to the re-positioning of the irido-lenticular complex. PMID- 27179668 TI - Mechanistic studies of the toxicity of zinc gluconate in the olfactory neuronal cell line Odora. AB - Zinc is both an essential and potentially toxic metal. It is widely believed that oral zinc supplementation can reduce the effects of the common cold; however, there is strong clinical evidence that intranasal (IN) zinc gluconate (ZG) gel treatment for this purpose causes anosmia, or the loss of the sense of smell, in humans. Using the rat olfactory neuron cell line, Odora, we investigated the molecular mechanism by which zinc exposure exerts its toxic effects on olfactory neurons. Following treatment of Odora cells with 100 and 200MUM ZG for 0-24h, RNA seq and in silico analyses revealed up-regulation of pathways associated with zinc metal response, oxidative stress, and ATP production. We observed that Odora cells recovered from zinc-induced oxidative stress, but ATP depletion persisted with longer exposure to ZG. ZG exposure increased levels of NLRP3 and IL-1beta protein levels in a time-dependent manner, suggesting that zinc exposure may cause an inflammasome-mediated cell death, pyroptosis, in olfactory neurons. PMID- 27179670 TI - Development of Novel Drug and Gene Delivery Carriers Composed of Single-Walled Carbon Nanotubes and Designed Peptides With PEGylation. AB - Single-walled carbon nanotubes (SWCNTs) attract great interest in biomedical applications including drug and gene delivery. In this study, we developed a novel delivery system using SWCNTs associated with designed polycationic and amphiphilic peptides. Wrapping of SWCNTs with H-(-Lys-Trp-Lys-Gly-)7-OH [(KWKG)7] resulted in stable dispersion in water, but the composite aggregated in the buffered solution. This dispersion instability was also evident in a cell culture medium with fetal bovine serum. To improve the aqueous dispersibility, the SWCNTs (KWKG)7 composite was further modified with polyethylene glycol (PEG) at the lysine residues via amide bond formation and the highest modification extent of 13.3% of the amino groups which corresponded to 2 PEG chains in each peptide molecule was achieved with fluorescein isothiocyanate-labeled carboxyl-PEG12. The uptake of the SWCNTs composite by A549 human lung adenocarcinoma epithelial cells was evaluated by visual observation and fluorescence activated cell sorting analysis for SWCNTs wrapped with a mixture of (KWKG)7 with PEGylation and H-(-Cys Trp-Lys-Gly-)-OH-(KWKG)6 [CWKG(KWKG)6] labeled with fluorescent boron dipyrromethene tetramethylrhodamine and 7-fold higher uptake comparing with SWCNTs-peptide composite without PEGylation was obtained suggesting the importance of dispersibility in addition to a cationic charge. The superior potential of SWCNTs composites assisted by polycationic and amphiphilic peptides with PEGylation was thus demonstrated. PMID- 27179671 TI - Enhanced Activity of Topical Hydrocortisone by Competitive Binding of Corticosteroid-Binding Globulin. AB - Atopic dermatitis of sensitive areas such as the face, particularly in children, is a difficult disease to treat as the standard therapeutic, topical steroids, is contraindicated for this application in children. Hydrocortisone (HC) can be used in these instances because it has been shown to be safe, but is often ineffective as it is a relatively weak steroid, especially at over-the-counter concentrations. To enhance the local topical activity of HC, the terminal inactive metabolite of prednisolone, Delta(1)-cortienic acid (Delta(1)-CA), is added to HC, as Delta(1)-CA preferentially binds transcortin, liberating more HC to elicit its therapeutic effect. Skin blanching studies, which are used to evaluate the potency of topical steroids, were employed to assess the ability of Delta(1)-CA to enhance the activity of HC. The results demonstrate that Delta(1) CA, when applied in combination with HC, does indeed potentiate the vasoconstriction effect of topically applied HC, while having no effect alone. Thus, addition of the inert prednisolone metabolite Delta(1)-CA can increase the therapeutic effect of over-the-counter concentrations of HC when applied topically. PMID- 27179672 TI - The Fast-Casual Conundrum: Fast-Casual Restaurant Entrees Are Higher in Calories than Fast Food. AB - BACKGROUND: Frequently eating fast food has been associated with consuming a diet high in calories, and there is a public perception that fast-casual restaurants (eg, Chipotle) are healthier than traditional fast food (eg, McDonald's). However, research has not examined whether fast-food entrees and fast-casual entrees differ in calorie content. OBJECTIVE: The purpose of this study was to determine whether the caloric content of entrees at fast-food restaurants differed from that found at fast-casual restaurants. DESIGN: This study was a cross-sectional analysis of secondary data. Calorie information from 2014 for lunch and dinner entrees for fast-food and fast-casual restaurants was downloaded from the MenuStat database. OUTCOME MEASURES: Mean calories per entree between fast-food restaurants and fast-casual restaurants and the proportion of restaurant entrees that fell into different calorie ranges were assessed. STATISTICAL ANALYSES PERFORMED: A t test was conducted to test the hypothesis that there was no difference between the average calories per entree at fast-food and fast-casual restaurants. To examine the difference in distribution of entrees in different calorie ranges between fast-food and fast-casual restaurants, chi(2) tests were used. RESULTS: There were 34 fast-food and 28 fast-casual restaurants included in the analysis (n=3,193 entrees). Fast-casual entrees had significantly more calories per entree (760+/-301 kcal) than fast-food entrees (561+/-268; P<0.0001). A greater proportion of fast-casual entrees compared with fast-food entrees exceeded the median of 640 kcal per entree (P<0.0001). CONCLUSIONS: Although fast-casual entrees contained more calories than fast-food entrees in the study sample, future studies should compare actual purchasing patterns from these restaurants to determine whether the energy content or nutrient density of full meals (ie, entrees with sides and drinks) differs between fast-casual restaurants and fast-food restaurants. Calorie-conscious consumers should consider the calorie content of entree items before purchase, regardless of restaurant type. PMID- 27179673 TI - Is It Possible to Prevent ARDS? PMID- 27179674 TI - Who Should Be Screened for Lung Cancer? And Who Gets to Decide? PMID- 27179675 TI - A liquid chromatography tandem mass spectrometric method on in vitro nerve agents poisoning characterization and reactivator efficacy evaluation by determination of specific peptide adducts in acetylcholinesterase. AB - The terroristic availability of highly toxic nerve agents (NAs) highlights the necessity for a deep understanding of their toxicities and effective medical treatments. A liquid chromatography tandem mass spectrometry (LC-MS/MS) method for a characterization of the NAs poisoning and an evaluation on the efficacy of reactivators in in vitro was developed for the first time. After exposure to sarin or VX and pepsin digestion, the specific peptides of acetylcholinesterase (AChE) in a purified status, i.e. undecapeptide "GESAGAASVGM" in free, unaged, or aged status was identified and quantified. A key termination procedure is focused to make the reaction system "frozen" and precisely "capture" the poisoning, aging and spontaneous reactivation status of AChE, and the abundance of such specific peptides can thus be simultaneously measured. In our established method, as low as 0.72% and 0.84% inhibition level of AChE induced by 0.5nM sarin and VX can be detected from the measurement of peptide adducts, which benefits a confirmation of NAs exposure, especially at extremely low levels. Comparing with conventional colorimetric Ellman assays, our method provides not only enzyme activity and inhibition rate, but also the precise poisoning status of NAs exposed AChE. Based on the full information provided by this method, the efficacy of reactivators, such as HI-6, obidoxime and pralidoxime, in the typical treatment of NAs poisoned AChE in in vitro was further evaluated. Our results showed that this method is a promising tool for the characterization of NAs poisoning and the evaluation of reactivator efficacy. PMID- 27179676 TI - Detection of 1,N(2)-propano-2'-deoxyguanosine adducts in genomic DNA by ultrahigh performance liquid chromatography-electrospray ionization-tandem mass spectrometry in combination with stable isotope dilution. AB - Crotonaldehyde (Cro) is one of widespread and genotoxic alpha,beta-unsaturated aldehydes and can react with the exocyclic amino group of 2'-deoxyguanosine (dG) in genomic DNA to form 1,N(2)-propano-2'-deoxyguanosine (ProdG) adducts. In this study, two diastereomers of high purity were prepared, including non-isotope and stable isotope labeled ProdG adducts, and exploited stable isotope dilution-based calibration method. By taking advantage of synthesized ProdG standards, we developed a sensitive ultrahigh performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UHPLC-ESI-MS/MS) method for accurate quantification of two diastereomers of ProdG adducts. In addition to optimization of the UHPLC separation, ammonium bicarbonate (NH4HCO3) was used as additive in the mobile phase for enhancing the ionization efficiency to ProdG adducts and facilitating MS detection. The limits of detection (LODs, S/N=3) and the limits of quantification (LOQs, S/N=10) are estimated about 50 amol and 150 amol, respectively. By the use of the developed method, both diastereomers of ProdG adducts can be detected in untreated human MRC5 cells with a frequency of 2.4-3.5 adducts per 10(8) nucleotides. Crotonaldehyde treatment dramatically increases the levels of ProdG adducts in human MRC5 in a concentration-dependent manner. PMID- 27179677 TI - Retention behavior of lipids in reversed-phase ultrahigh-performance liquid chromatography-electrospray ionization mass spectrometry. AB - Reversed-phase ultrahigh-performance liquid chromatography (RP-UHPLC) method using two 15cm sub-2MUm particles octadecylsilica gel columns is developed with the goal to separate and unambiguously identify a large number of lipid species in biological samples. The identification is performed by the coupling with high resolution tandem mass spectrometry (MS/MS) using quadrupole - time-of-flight (QTOF) instrument. Electrospray ionization (ESI) full scan and tandem mass spectra are measured in both polarity modes with the mass accuracy better than 5ppm, which provides a high confidence of lipid identification. Over 400 lipid species covering 14 polar and nonpolar lipid classes from 5 lipid categories are identified in total lipid extracts of human plasma, human urine and porcine brain. The general dependences of relative retention times on relative carbon number or relative double bond number are constructed and fit with the second degree polynomial regression. The regular retention patterns in homologous lipid series provide additional identification point for UHPLC/MS lipidomic analysis, which increases the confidence of lipid identification. The reprocessing of previously published data by our and other groups measured in the RP mode and ultrahigh-performance supercritical fluid chromatography on the silica column shows more generic applicability of the polynomial regression for the description of retention behavior and the prediction of retention times. The novelty of this work is the characterization of general trends in the retention behavior of lipids within logical series with constant fatty acyl length or double bond number, which may be used as an additional criterion to increase the confidence of lipid identification. PMID- 27179678 TI - Kinetic plots for programmed temperature gas chromatography. AB - The applicability of the kinetic plot theory to temperature-programmed gas chromatography (GC) has been confirmed experimentally by measuring the efficiency of a temperature gradient separation of a simple test mixture on 15, 30, 60 and 120m long (coupled) columns. It has been shown that the temperature-dependent data needed for the kinetic plot calculation can be obtained from isothermal experiments at the significant temperature, a temperature that characterizes the entire gradient run. Furthermore, optimal flow rates have been calculated for various combinations of column length, diameter, and operating temperature (or significant temperature). The tabulated outcome of these calculations provide good starting points for the optimization of any GC separation. PMID- 27179679 TI - Association between size-segregated particles in ambient air and acute respiratory inflammation. AB - The health effects of particulate matter (PM) in ambient air are well documented. However, whether PM size plays a critical role in these effects is unclear in the population studies. This study investigated the association between the ambient concentrations of PM with varies sizes (5.6-560nm) and a biomarker of acute respiratory inflammation, the fraction of exhaled nitric oxide (FENO), in a panel of 55 elderly people in Shanghai, China. Linear mixed-effect model was fitted to estimate the association between FENO and moving average concentrations of PM, adjusting for temperature, relative humidity, day of the week, and age. Results showed that among the measured particles size range, Aitken-mode (20-100nm) particles had the strongest positive association with increased FENO when using moving average concentration of PM up to 24h prior to visits. The estimates were robust to the adjustment for gender, condition of chronic disease and use of medication, and to the sensitive analysis using different times of visits. The authors concluded that the association between acute respiratory inflammation and PM concentration of fine particulates depended on particle size, and suggested Aitken-mode particles may be the most responsible for this adverse health association. PMID- 27179680 TI - Exploring a suitable nitrogen fertilizer rate to reduce greenhouse gas emissions and ensure rice yields in paddy fields. AB - The application rate of nitrogen fertilizer was believed to dramatically influence greenhouse gas (GHG) emissions from paddy fields. Thus, providing a suitable nitrogen fertilization rate to ensure rice yields, reducing GHG emissions and exploring emission behavior are important issues for field management. In this paper, a two year experiment with six rates (0, 75, 150, 225, 300, 375kgN/ha) of nitrogen fertilizer application was designed to examine GHG emissions by measuring carbon dioxide (CO2), methane (CH4), nitrous oxide (N2O) flux and their cumulative global warming potential (GWP) from paddy fields in Hangzhou, Zhejiang in 2013 and 2014. The results indicated that the GWP and rice yields increased with an increasing application rate of nitrogen fertilizer. Emission peaks of CH4 mainly appeared at the vegetative phase, and emission peaks of CO2, and N2O mainly appeared at reproductive phase of rice growth. The CO2 flux was significantly correlated with soil temperature, while the CH4 flux was influenced by logging water remaining period and N2O flux was significantly associated with nitrogen application rates. This study showed that 225kgN/ha was a suitable nitrogen fertilizer rate to minimize GHG emissions with low yield scaled emissions of 3.69 (in 2013) and 2.23 (in 2014) kg CO2-eq/kg rice yield as well as to ensure rice yields remained at a relatively high level of 8.89t/ha in paddy fields. PMID- 27179681 TI - A stochastic dynamic model to assess land use change scenarios on the ecological status of fluvial water bodies under the Water Framework Directive. AB - This method development paper outlines an integrative stochastic dynamic methodology (StDM) framework to anticipate land use (LU) change effects on the ecological status of monitored and non-monitored lotic surface waters under the Water Framework Directive (WFD). Tested in the Alto Minho River Basin District in North West Portugal, the model is an innovative step towards developing a decision-making and planning tool to assess the influence impacts such as LU change and climate change on these complex systems. Comprising a series of sequential steps, a Generalized Linear Model based, competing model Multi Model Inference (MMI) approach was used for parameter estimation to identify principal land use types (distal factors) driving change in biological and physicochemical support elements (proximal factors) in monitored water bodies. The framework integrated MMI constants and coefficients of selected LU categories in the StDM simulations and spatial projections to simulate the ecological status of monitored and non-monitored lotic waterbodies in the test area under 2 scenarios of (1) LU intensification and (2) LU extensification. A total of 100 simulations were run for a 50year period for each scenario. Spatially dynamic projections of WFD metrics were obtained, taking into account the occurrence of stochastic wildfire events which typically occur in the study region and are exacerbated by LU change. A marked projected decline to "Moderate" ecological status for most waterbodies was detected under intensification but little change under extensification; only a few waterbodies fell to "moderate" status. The latter scenario describes the actual regional socio-economic situation of agricultural abandonment due to rural poverty, partly explaining the projected lack of change in ecological status. Based on the WFD "one out all out" criterion, projected downward shifts in ecological status were due to physicochemical support elements, namely increased phosphorus levels. Little or no change in status was driven by Intercalibrated Biological Quality Elements, indicating innate resilience and raising questions concerning uncertainty, the effect of pressures other than land use and metric redundancy and the WFD classification process. PMID- 27179683 TI - Phenylbenzoisoquinolindione alkaloids accumulate in stamens of Xiphidium caeruleum Aubl. flowers. AB - Xiphidium caeruleum (Haemodoraceae) flower organs such as carpels, pedicels, petals, and stamens were separately investigated for their phytochemical profile. The stamens appeared to be a rich source of previously undescribed phenylbenzoisoquinolindiones, a group of phenylphenalenone-derived alkaloids, also named aza-phenylphenalenones. Nine previously undescribed compounds with an identical aza-phenylphenalenone core structure but different amino acid-derived side chains at position 2 were isolated and their structures elucidated by nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS). In addition, some previously reported phenylbenzoisoquinolindiones, phenylbenzoisochromenones and flavonoids were found in stamens and other parts of the flowers. The specific occurrence of heterocyclic phenylphenalenone-type compounds in X. caeruleum suggests these are involved in physiological or ecological processes. PMID- 27179682 TI - Association of Panton Valentine Leukocidin (PVL) genes with methicillin resistant Staphylococcus aureus (MRSA) in Western Nepal: a matter of concern for community infections (a hospital based prospective study). AB - BACKGROUND: Methicillin resistant Staphylococcus aureus (MRSA) is a major human pathogen associated with nosocomial and community infections. Panton Valentine leukocidin (PVL) is considered one of the important virulence factors of S. aureus responsible for destruction of white blood cells, necrosis and apoptosis and as a marker of community acquired MRSA. This study was aimed to determine the prevalence of PVL genes among MRSA isolates and to check the reliability of PVL as marker of community acquired MRSA isolates from Western Nepal. METHODS: A total of 400 strains of S. aureus were collected from clinical specimens and various units (Operation Theater, Intensive Care Units) of the hospital and 139 of these had been confirmed as MRSA by previous study. Multiplex PCR was used to detect mecA and PVL genes. Clinical data as well as antimicrobial susceptibility data was analyzed and compared among PVL positive and negative MRSA isolates. RESULTS: Out of 139 MRSA isolates, 79 (56.8 %) were PVL positive. The majority of the community acquired MRSA (90.4 %) were PVL positive (Positive predictive value: 94.9 % and negative predictive value: 86.6 %), while PVL was detected only in 4 (7.1 %) hospital associated MRSA strains. None of the MRSA isolates from hospital environment was found positive for the PVL genes. The majority of the PVL positive strains (75.5 %) were isolated from pus samples. Antibiotic resistance among PVL negative MRSA isolates was found higher as compared to PVL positive MRSA. CONCLUSION: Our study showed high prevalence of PVL among community acquired MRSA isolates. Absence of PVL among MRSA isolates from hospital environment indicates its poor association with hospital acquired MRSA and therefore, PVL may be used a marker for community acquired MRSA. This is first study from Nepal, to test PVL among MRSA isolates from hospital environment. PMID- 27179684 TI - Phytochemical study and biological evaluation of chemical constituents of Platanus orientalis and Platanus * acerifolia buds. AB - One flavonol glycoside, two O-isoprenylated flavonols, one alpha,alpha dimethylallyl flavonol, one dihydrochalcone, two furanocoumarins and one terpenoid previously undescribed, along with 42 known compounds were isolated from the buds of two European Platanaceae, Platanus orientalis and Platanus * acerifolia. Their chemical structures were elucidated on the basis of spectroscopic analysis, including homonuclear and heteronuclear correlation NMR (COSY, NOESY, HSQC, and HMBC) experiments, as well as HRMS data. The estrogen like and antiestrogen-like activity of dichloromethane and methanol extracts of P. orientalis and P. * acerifolia buds and isolated compounds was evaluated using estrogen-responsive cell lines. The potency of selected estrogen agonists to regulate gene expression through ERalpha and/or ERbeta was compared with their in vitro osteoblastogenic activity. Kaempferol and 8-C-(1,1-dimethyl-2-propen-1-yl) 5,7-dihydroxyflavonol displayed osteoblastogenic as well as ERalpha-mediated estrogenic activity similar to estradiol. PMID- 27179685 TI - Anthocyanins of the anthers as chemotaxonomic markers in the genus Populus L.. Differentiation between Populus nigra, Populus alba and Populus tremula. AB - Three main species of Popululs L. (Salicaceae) have been reported to occur in the Iberian Peninsula: Populus nigra L., Populus alba L. and Populus tremula L. The degree of pilosity of the bracts of the male catkins is a key character for their differentiation. The anthers of these poplar species possess anthocyanins that provide them a red colouration. Since these poplars are wind-pollinated and, consequently, do not need to attract pollinators, anthocyanins in the anthers might be acting as photoprotectors, shielding pollen grains from excessive sunlight. In order to verify this hypothesis, the first objective of this study was to establish if there is any relationship between the degree of pilosity of the bracts (related to the physical shading of the pollen grains) and the levels and types of anthocyanins in the anthers of these three species. This study also aimed to check the usefulness of the anthocyanins of the anthers as chemotaxonomic markers, through the study of the differences in the anthocyanin composition between these poplar species. Anthocyanins were identified from the data supplied by HPLC-DAD-MS(n) analyses. Seventeen different compounds, including mono-, di- and triglycosides and anthocyanin-derived pigments (F-A(+) dimers) have been identified. Cyanidin 3-O-glucoside was the major compound in all the samples (>60% of the total content), which may be in accordance with the photoprotective role proposed for them. However, qualitative and quantitative differences were detected among samples. Cyanidin and delphinidin 3-O sambubiosides have been detected only in the anthers of P. tremula as well as cyanidin 3-O-(2"-O-xyloxyl)rutinoside, making them valuable chemotaxonomic markers for this species. Hierarchical Cluster and Principal Components Analyses (HCA and PCA) carried out with the anthocyanin percent composition data have allowed a separation of the samples that is in accordance with the initial classification of the samples made from the morphological characters of the specimens. Furthermore, these analyses have revealed intraspecific differences among samples that point out to different clones or varieties of a same species. PMID- 27179686 TI - Hey, brother neutrophil, what are you up to? PMID- 27179687 TI - A case of ampullary follicular lymphoma. PMID- 27179688 TI - Transhepatic tract for visualization of the remnant stomach after Roux-en-Y gastric bypass. PMID- 27179689 TI - A new quality indicator of colonoscopy: caveat emptor. PMID- 27179690 TI - Common bile duct duplication: double bile ducts, double trouble. PMID- 27179691 TI - Early gastric cancer on submucosal heterotopic gastric glands. PMID- 27179692 TI - Structure, IR and Raman spectra of phosphotrihydrazide studied by DFT. AB - The FTIR and FT Raman measurements of the phosphotrihydrazide (S)P[N(Me)-NH2]3 have been performed. This compound is a zero generation dendrimer G0 with terminal amine groups. Structural optimization and normal mode analysis were obtained for G0 by the density functional theory (DFT). Optimized geometric bond length and angles obtained by DFT show good agreement with experiment. The amine terminal groups are characterized by the well-defined bands at 3321, 3238, 1614cm(-1) in the experimental IR spectrum and by bands at 3327, 3241cm(-1) in the Raman spectrum of G0. The experimental frequencies of asymmetric and symmetric NH2 stretching vibrations of amine group are lower than theoretical values due to intramolecular NH?S hydrogen bond. This hydrogen bond is also responsible for higher experimental infrared intensity of these bands as compared with theoretical values. Relying on DFT calculations a complete vibrational assignment is proposed for the studied dendrimer. PMID- 27179693 TI - A randomized, sham-controlled study of high frequency rTMS for auditory hallucination in schizophrenia. AB - Chronic auditory verbal hallucinations (AVHs) in patients with schizophrenia are sometimes resistant to standard pharmacotherapy. Repetitive transcranial magnetic stimulation (rTMS) may be a promising treatment modality for AVHs, but the best protocol has yet to be identified. We used a double-blind randomized sham controlled design aimed at 30 patients (active group N=16 vs. sham group N=14) with chronic AVHs that persisted regardless of adequate pharmacotherapy. The protocol was a total of four sessions of high-frequency (20-Hz) rTMS targeting the left temporoparietal cortex over 2 days (total 10,400 stimulations) administered to each patient. After the rTMS session the patients were followed for 4 weeks and evaluated with the Auditory Hallucination Rating Scale (AHRS). The mean changes of AHRS score were 22.9 (baseline) to 18.4 (4th week) in the Active group and 24.2 (baseline) to 21.8 (4th week) in the Sham group, indicating no significant difference by mix model analysis. As regards other secondary end points (each subscore of AHRS, BPRS, GAF and CGI-S), none of these parameters showed a significant between-group difference. The present study's rTMS protocol was ineffective for our patients. However, several previous studies demonstrated that high-frequency rTMS is a possible strategy to ameliorate pharmacotherapy resistant AVH. It is important to establish a high-frequency rTMS protocol with more reliability. PMID- 27179694 TI - Behavioral predispositions to approach or avoid emotional words in schizophrenia. AB - Many data suggest a disjunction between decreased emotional expressions and relatively preserved experience of and ability to assess emotions in schizophrenia. Based in an embodied approach of cognition, several studies have highlighted affective stimulus-response congruency effect in healthy subjects that show a direct link between the perception of emotion and associated motor responses. This study investigated whether the categorization of emotional words involves an automatic sensorimotor simulation of approach and avoidance behaviors. We asked 28 subjects with schizophrenia and 28 controls to execute arm movements of approach or avoidance to categorize emotional words, according to their valence (positive or negative). Controls were faster to respond to a positive stimulus with a movement of approach and a negative stimulus with a movement of avoidance (congruent condition) than to perform the inverted response movements (incongruent condition). However, responses of patients with schizophrenia did not differ according to congruence condition. Our results support the apparent non-involvement of covert sensorimotor simulation of approach and avoidance in the categorization of emotional stimuli by patients with schizophrenia, despite their understanding of the emotional valence of words. This absence of affective stimulus-response compatibility effect would imply a decoupling between emotional and bodily states in patients with schizophrenia. PMID- 27179695 TI - Estrogen receptor beta modulates breast cancer cells functional properties, signaling and expression of matrix molecules. AB - Estrogen receptors have pivotal roles in breast cancer growth and progression. ERalpha has been clearly shown to play key role in hormone-dependent breast cancer properties, but little is known for the isoform ERbeta. To evaluate the role of ERbeta, we established stably transfected ERbeta-suppressed MDA-MB-231 breast cancer cells by knocking down the human ERbeta gene, using specific shRNA lentiviral particles. As observed by scanning electron microscopy, the ERbeta suppression induces significant phenotypic changes in these cells, as compared to the control cells. Notably, the down-regulation of ERbeta decreases the expression of the mesenchymal markers fibronectin and vimentin, whereas it increases the expression levels of the epithelial marker E-cadherin and cell junctions. These alterations are followed by reduced levels of the functional cell properties that promote the aggressiveness of these cells, such as proliferation, migration, spreading capacity, invasion and adhesion on collagen I. Notably, the down-regulation of ERbeta reduces the migration of breast cancer cells through the tyrosine kinase receptors EGFR/IGF-IR and the JAK/STAT signaling pathways. Moreover, ERbeta has a crucial role on the gene expression of several matrix mediators, including the proteoglycans syndecans-2/-4 and serglycin, several matrix metalloproteinases, plasminogen activation system components and receptor tyrosine kinases. These data clearly show that ERbeta plays a crucial role in the cell behavior and ECM composition of the highly aggressive MDA-MB-231 cells and opens a new area of research to further understand its role and to improve pharmaceutical targeting of the non-hormone dependent breast cancer. PMID- 27179697 TI - Simulation of tumor induced angiogenesis using an analytical adaptive modeling including dynamic sprouting and blood flow modeling. AB - In this paper, an adaptive model for tumor induced angiogenesis is developed that integrates generation and diffusion of a growth factor originated from hypoxic cells, adaptive sprouting from a parent vessel, blood flow and structural adaptation. The proposed adaptive sprout spacing model (ASS) determines position, time and number of sprouts which are activated from a parent vessel and also the developed vascular network is modified by a novel sprout branching prediction algorithm. This algorithm couples local vascular endothelial growth factor (VEGF) concentrations, stresses due to the blood flow and stochastic branching to the structural reactions of each vessel segment in response to mechanical and biochemical stimuli. The results provide predictions for the time-dependent development of the network structure, including the position and diameters of each segment and the resulting distributions of blood flow and VEGF. Considering time delays between sprout progressions and number of sprouts activated at different time durations provides information about micro-vessel density in the network. Resulting insights could be useful for motivating experimental investigations of vascular pattern in tumor induced angiogenesis and development of therapies targeting angiogenesis. PMID- 27179696 TI - An unregulated regulator: Vasa expression in the development of somatic cells and in tumorigenesis. AB - Growing evidence in diverse organisms shows that genes originally thought to function uniquely in the germ line may also function in somatic cells, and in some cases even contribute to tumorigenesis. Here we review the somatic functions of Vasa, one of the most conserved "germ line" factors among metazoans. Vasa expression in somatic cells is tightly regulated and often transient during normal development, and appears to play essential roles in regulation of embryonic cells and regenerative tissues. Its dysregulation, however, is believed to be an important element of tumorigenic cell regulation. In this perspectives paper, we propose how some conserved functions of Vasa may be selected for somatic cell regulation, including its potential impact on efficient and localized translational activities and in some cases on cellular malfunctioning and tumorigenesis. PMID- 27179699 TI - Untangling a species complex of arid zone grasses (Triodia) reveals patterns congruent with co-occurring animals. AB - The vast Australian arid zone formed over the last 15million years, and gradual aridification as well as more extreme Pliocene and Pleistocene climate shifts have impacted the evolution of its biota. Understanding the evolutionary history of groups of organisms or regional biotas such as the Australian arid biota requires clear delimitation of the units of biodiversity (taxa). Here we integrate evidence from nuclear (ETS and ITS) and chloroplast (rps16-trnK spacer) regions and morphology to clarify taxonomic boundaries in a species complex of Australian hummock grasses (Triodia) to better understand the evolution of Australian arid zone plants and to evaluate congruence in distribution patterns with co-occurring organisms. We find evidence for multiple new taxa in the T. basedowii species complex, but also incongruence between data sets and indications of hybridization that complicate delimitation. We find that the T. basedowii complex has high lineage diversity and endemism in the biologically important Pilbara region of Western Australia, consistent with the region acting as a refugium. Taxa show strong geographic structure in the Pilbara, congruent with recent work on co-occurring animals and suggesting common evolutionary drivers across the biota. Our findings confirm recognition of the Pilbara as an important centre of biodiversity in the Australian arid zone, and provide a basis for future taxonomic revision of the T. basedowii complex and more detailed study of its evolutionary history and that of arid Australia. PMID- 27179698 TI - The Challenges and Solutions for Cadmium-contaminated Rice in China: A Critical Review. AB - The wide occurrence of Cd-contaminated rice in southern China poses significant public health risk and deserves immediate action, which arises primarily from extensive metal (including Cd) contamination of paddies with the fast expansion of nonferrous metal mining and smelting activities. Accumulation of Cd in rice grains can be reduced by removing Cd from the contaminated paddy soils, reducing its bioavailability, and controlling its uptake by rice plants. Although a range of measures can be taken to rehabilitate Cd-contaminated lands, including soil replacement and turnover, chemical washing, and phytoremediation, they are either too expensive and/or too slow. Various amendment materials, including lime, animal manures, and biochar, can be used to immobilize Cd in soils, but such fixation approach can only temporarily reduce Cd availability to rice uptake. Cultivation of alternative crops with low Cd accumulation in edible plant parts is impractical on large scales due to extensive contamination and food security concerns in southern China. Transgenic techniques can help develop rice cultivars with low Cd accumulation in grains, but little public acceptance is expected for such products. As an alternative, selection and development of low-Cd rice varieties and hybrids through plant biotechnology and breeding, particularly, by integration of marker-assisted selection (MAS) with traditional breeding, could be a practical and acceptable option that would allow continued rice production in soils with high bioavailability of Cd. Plant biotechnology and breeding can also help develop Cd-hyperaccumulating rice varieties, which can greatly facilitate phytoremediation of contaminated paddies. To eliminate the long-term risk of Cd entering the food chain, soils contaminated by Cd should be cleaned up when cost-effective remediation measures are available. PMID- 27179700 TI - Molecular and morphological phylogenetics of chelonine parasitoid wasps (Hymenoptera: Braconidae), with a critical assessment of divergence time estimations. AB - Parasitoid wasps of the subfamily Cheloninae are both species rich and poorly known. Although the taxonomy of Cheloninae appears to be relatively stable, there is no clear understanding of relationships among higher-level taxa. We here applied molecular phylogenetic analyses using three markers (COI, EF1alpha, 28S) and 37 morphological characters to elucidate the evolution and systematics of these wasps. Analyses were based on 83 specimens representing 13 genera. All genera except Ascogaster, Phanerotoma, and Pseudophanerotoma formed monophyletic groups; Furcidentia (stat. rev.) is raised to generic rank. Neither Chelonus (Chelonus) nor Chelonus (Microchelonus) were recovered as monophyletic, but together formed a monophyletic lineage. The tribes Chelonini and Odontosphaeropygini formed monophyletic groups, but the Phanerotomini sensu Zettel and Pseudophanerotomini were retrieved as either para- or polyphyletic. The genera comprising the former subfamily Adeliinae were confirmed as being nested within the Cheloninae. To estimate the age of the subfamily, we used 16 fossil taxa. Three approaches were compared: fixed-rate dating, node dating, and total-evidence dating, with age estimates differing greatly between the three methods. Shortcomings of each approach in relation to our dataset are discussed, and none of the age estimates is deemed sufficiently reliable. Given that most dating studies use a single method only, in most cases without presenting analyses on the sensitivity to priors, it is likely that numerous age estimates in the literature suffer from a similar lack of robustness. We argue for a more rigorous approach to dating analyses and for a faithful presentation of uncertainties in divergence time estimates. Given the results of the phylogenetic analysis the following taxonomic changes are proposed: Furcidentia Zettel (stat. rev.), previously treated as a subgenus of Pseudophanerotoma Zettel is raised to generic rank; Microchelonus Szepligeti (syn. nov.), variously treated by previous authors, is proposed as a junior synonym of Chelonus Jurine; the following subgenera of Microchelonus - Baculonus Braet & van Achterberg (syn. nov.), Carinichelonus Tobias (syn. nov.) and Scabrichelonus He, Chen & van Achterberg (syn. nov.), are proposed as junior synonyms of Chelonus; a number of new species names are proposed due to homonyms resulting from the above changes and these are listed in the paper. PMID- 27179701 TI - Microwave-induced synthesis of pyrophosphate Zr1-xTixP2O7 and TiP2O7 with enhanced sorption capacity for uranium (VI). AB - A series of nanostructured pyrophosphates Zr1-xTixP2O7 (x=0, 0.2, 0.4, 0.5, 0.6, 0.8, and 1.0), have been prepared via a facile microwave induced route in which zirconium hydroxide, titanium hydroxide and phosphoric acid were used as Zr, Ti and P sources, respectively. It is demonstrated the isomorphous substitution of Zr(4+) by Ti(4+) results in a decrease of the size and an enhancement of the adsorption capacity of the obtained particles for U(VI) in aqueous solution. The maximum amount of TiP2O7 for U(VI) reached up to 309.8 mgg(-1) under the experimental conditions (pH=5, t=60min and T=303K). The as-obtained specific metal pyrophosphates exhibit a considerably higher adsorption capability for U(VI) in aqueous solution compared with Zr1-xTixP2O7 prepared by calcined method, showing a high potential for U(VI) sequestration applications. The adsorption kinetics and thermodynamic analysis of Zr1-xTixP2O7 on adsorption of U (VI) were performed, and a possible adsoprtion mechanism was also proposed. PMID- 27179702 TI - A multicenter study of biological effects assessment of pharmacy workers occupationally exposed to antineoplastic drugs in Pharmacy Intravenous Admixture Services. AB - This multi-centered study was designed to evaluate the biological effects of exposure to antineoplastic drugs (ADs) at PIVAS (Pharmacy Intravenous Admixture Service) across ten Chinese hospitals. 8-hydroxy-2-deoxyguanosine (8-OHdG) was used as a biomarker of DNA oxidative damage and lymphocyte apoptosis assays using peripheral lymphocyte cells were used to detect primary DNA damage. The mutagenicity activity was estimated with the Ames fluctuation test. 158 exposed and 143 unexposed workers participated in this study. The urinary 8-OHdG/Cr concentrations of the exposed group was 22.05+/-17.89ng/mg Cr, which was significantly higher than controls of 17.36+/-13.50ng/mg Cr (P<0.05). The rate of early lymphocyte apoptosis was slightly increased in exposed group than that of the control group (P=0.087). The mutagenic activity was significantly higher in the exposed group relative to the control group (P<0.05). Moreover, while no statistically significant difference was observed, higher concentrations of 8 OHdG/Cr in urine and an early lymphocyte apoptosis rate were found in exposed group II as compared to exposed group I. In addition, a significant correlation between early lymphocyte apoptosis and exposure time to ADs was also observed (P<0.05). In conclusion, our study identified elevated biomarkers in PIVAS workers exposed to ADs. However whether these findings could lead to increased incidence of genotoxic responses remains to be further investigated. PMID- 27179704 TI - A novel reutilization method for waste printed circuit boards as flame retardant and smoke suppressant for poly (vinyl chloride). AB - In this study, a novel reutilization method for waste printed circuit boards (PCBs) as flame retardant and smoke suppressant for poly (vinyl chloride) (PVC) was successfully testified. A supercritical water oxidation (SCWO) process was applied to treat waste PCBs before they could be used as flame retardants of PVC. The results indicated that SCWO conditions had a significant effect on the flame retarding and smoke suppressing properties of waste PCBs for PVC. Cu2O, CuO, and SnO2 were the main active ingredients in waste PCBs-derived flame retardants. A conversion of Cu elements (Cu(0)->Cu(+)->Cu(2+)) during SCWO process with the increase of reaction temperature was found to be the key influence factor for the flame retarding properties of SCWO-treated PCBs. The experiment results also showed that there was a synergistic effect of flame retardancy between Cu(+) and Cu(2+). After the optimized SCWO treatment, SCWO-treated PCBs significantly improved the flame retardancy and smoke suppression of PVC. Limiting oxygen index (LOI) and char yield (CY) increased with increasing SCWO-treated PCBs content in PVC, while smoke density rating (SDR) and maximum smoke density (MSD) decreased markedly. The mechanical properties of PVC samples were influenced in different degree by adding different content SCWO-treated PCBs. PMID- 27179703 TI - Human migration activities drive the fluctuation of ARGs: Case study of landfills in Nanjing, eastern China. AB - Landfills are perfect sites to study the effect of human migration on fluctuation of antibiotic resistance genes (ARGs) as they are the final destination of municipal waste. For example, large-scale human migration during the holidays is often accompanied by changes in waste dumping having potential effects on ARG abundance. Three landfills were selected to examine fluctuation in the abundance of fifteen ARGs and Intl1 genes for 14 months in Nanjing, eastern China. Mass human migration, the amount of dumped waste and temperature exerted the most significant effects on bimonthly fluctuations of ARG levels in landfill sites. As a middle-sized cosmopolitan city in China, millions of college students and workers migrate during holidays, contributing to the dramatic increases in waste production and fluctuation in ARG abundances. In line with this, mass migration explained most of the variation in waste dumping. The waste dumping also affected the bioaccessibility of mixed-compound pollutants that further positively impacted the level of ARGs. The influence of various bioaccessible compounds on ARG abundance followed the order: antibiotics>nutrients>metals>organic pollutants. Concentrations of bioaccessible compounds were more strongly correlated with ARG levels compared to total compound concentrations. Improved waste classification and management strategies could thus help to decrease the amount of bioaccessible pollutants leading to more effective control for urban ARG dissemination. PMID- 27179705 TI - Complement-here, there and everywhere, but what about the transplanted organ? AB - The part of the innate immune system that communicates and effectively primes the adaptive immune system was termed "complement" by Ehrlich to reflect its complementarity to antibodies having previously been described as "alexine" (i.e protective component of serum) by Buchner and Bordet. It has been established that complement is not solely produced systemically but may have origin in different tissues where it can influence organ specific functions that may affect the outcome of transplanted organs. This review looks at the role of complement in particular to kidney transplantation. We look at current literature to determine whether blockade of the peripheral or central compartments of complement production may prevent ischaemic reperfusion injury or rejection in the transplanted organ. We also review new therapeutics that have been developed to inhibit components of the complement cascade with varying degrees of success leading to an increase in our understanding of the multiple triggers of this complex system. In addition, we consider whether biomarkers in this field are effective markers of disease or treatment. PMID- 27179706 TI - Identification of novel APOB mutations by targeted next-generation sequencing for the molecular diagnosis of familial hypobetalipoproteinemia. AB - BACKGROUND AND AIMS: Familial hypobetalipoproteinemia (FHBL) is a co-dominant disorder characterized by decreased plasma levels of LDL-cholesterol and apolipoprotein B (ApoB). Currently, genetic diagnosis in FHBL relies largely on Sanger sequencing to identify APOB and PCSK9 gene mutations and on western blotting to detect truncated ApoB species. METHODS: Here, we applied targeted enrichment and next-generation sequencing (NGS) on a panel of three FHBL genes and two abetalipoproteinemia genes (APOB, PCSK9, ANGPTL3, MTTP and SAR1B). RESULTS: In this study, we identified five likely pathogenic heterozygous rare variants. These include four novel nonsense mutations in APOB (p.Gln845*, p.Gln2571*, p.Cys2933* and p.Ser3718*) and a rare variant in PCSK9 (Minor Allele Frequency <0.1%). The affected family members tested were shown to be carriers, suggesting co-segregation with low LDL-C. CONCLUSIONS: Our study further demonstrates that NGS is a reliable and practical approach for the molecular screening of FHBL-causative genes that may provide a mean for deciphering the genetic basis in FHBL. PMID- 27179707 TI - Inverse association of total testosterone with central haemodynamics and left ventricular mass in hypertensive men. AB - BACKGROUND: There is evidence for inverse association between endogenous testosterone and blood pressure. Furthermore, low plasma testosterone is associated with increased risk of major cardiovascular events in middle-aged hypertensive men. Central (aortic) blood pressures determine left ventricular hypertrophy and predict cardiovascular mortality. The aim of the present study was to assess the relationship of total testosterone (TT) with central haemodynamics and left ventricular mass in hypertensive men. METHODS: We investigated 134 non-diabetic, middle-aged, hypertensive men and 60 age-matched normotensive males. All participants were subject to measurement of aortic systolic (aoSBP) and pulse pressure (aoPP) by pulse wave analysis using the SphygmoCor device. Wave reflections were assessed by the measurement of heart rate corrected augmentation index (AIx75). Echocardiography was performed in all individuals and left ventricular mass (LVM) was calculated using the Devereux's formula. Plasma TT was measured by enzyme immunoassay. RESULTS: In hypertensive men, univariate analysis showed an inverse, significant correlation between TT and aoSBP (r = -20, p = 0.02), aoPP (r = -0.21, p = 0.01), AIx75 (r = -0.22, p = 0.01) and LVM (r = -0.19, p = 0.008). Multivariate regression analysis demonstrated an independent inverse association of TT with aoPP (b = -0.21, p = 0.02), AIx75 (b = -0.19, p = 0.03) and LVM (b = -0.28, p = 0.005) after adjustment for age, BMI, smoking, total cholesterol, triglycerides, fasting glucose, mean arterial pressure, antihypertensive treatment and statin use. Independent associations were retained even after inclusion of normotensive subjects in the analysis. CONCLUSIONS: In hypertensive men, TT is independently and inversely associated with central pulse pressure, wave reflections and left ventricular mass. Considering the adverse prognostic role of central blood pressures and LV hypertrophy on cardiovascular outcomes in hypertensive patients, the present findings might explain part of the increased cardiovascular risk associated with low testosterone. Whether measurement of central haemodynamics may improve risk stratification in hypertensive men with low testosterone warrants further investigation. PMID- 27179708 TI - Comparison of 3-dimensional dose reconstruction system between fluence-based system and dose measurement-guided system. AB - COMPASS system (IBA Dosimetry, Schwarzenbruck, Germany) and ArcCHECK with 3DVH software (Sun Nuclear Corp., Melbourne, FL) are commercial quasi-3-dimensional (3D) dosimetry arrays. Cross-validation to compare them under the same conditions, such as a treatment plan, allows for clear evaluation of such measurement devices. In this study, we evaluated the accuracy of reconstructed dose distributions from the COMPASS system and ArcCHECK with 3DVH software using Monte Carlo simulation (MC) for multi-leaf collimator (MLC) test patterns and clinical VMAT plans. In a phantom study, ArcCHECK 3DVH showed clear differences from COMPASS, measurement and MC due to the detector resolution and the dose reconstruction method. Especially, ArcCHECK 3DVH showed 7% difference from MC for the heterogeneous phantom. ArcCHECK 3DVH only corrects the 3D dose distribution of treatment planning system (TPS) using ArcCHECK measurement, and therefore the accuracy of ArcCHECK 3DVH depends on TPS. In contrast, COMPASS showed good agreement with MC for all cases. However, the COMPASS system requires many complicated installation procedures such as beam modeling, and appropriate commissioning is needed. In terms of clinical cases, there were no large differences for each QA device. The accuracy of the compass and ArcCHECK 3DVH systems for phantoms and clinical cases was compared. Both systems have advantages and disadvantages for clinical use, and consideration of the operating environment is important. The QA system selection is depending on the purpose and workflow in each hospital. PMID- 27179709 TI - Machine learning optimization of cross docking accuracy. AB - Performance of small molecule automated docking programs has conceptually been divided into docking -, scoring -, ranking - and screening power, which focuses on the crystal pose prediction, affinity prediction, ligand ranking and database screening capabilities of the docking program, respectively. Benchmarks show that different docking programs can excel in individual benchmarks which suggests that the scoring function employed by the programs can be optimized for a particular task. Here the scoring function of Smina is re-optimized towards enhancing the docking power using a supervised machine learning approach and a manually curated database of ligands and cross docking receptor pairs. The optimization method does not need associated binding data for the receptor-ligand examples used in the data set and works with small train sets. The re-optimization of the weights for the scoring function results in a similar docking performance with regard to docking power towards a cross docking test set. A ligand decoy based benchmark indicates a better discrimination between poses with high and low RMSD. The reported parameters for Smina are compatible with Autodock Vina and represent ready-to-use alternative parameters for researchers who aim at pose prediction rather than affinity prediction. PMID- 27179710 TI - Streptococcus mutans photoinactivation using a combination of a high potency photopolymerizer and rose bengal. AB - BACKGROUND: Long treatment periods to reach a substantial inactivation of microorganisms are one of the critical challenges in the photodynamic therapy field. METHODS: Planktonic suspensions of Streptococcus mutans were treated in different groups: presence of rose bengal (RB at 2MUM) and light exposure by a new high potency photopolymerizer (L at wavelength=440-480nm; dosimetry=96J/cm(2) - 40s of irradiation; potency density=1200mW/cm(2); dosage=48J) - RB+L+ (PDT), just with dye - RB+L-, just with light - RB-L+ and absence of light and dye RB-L- (control group). Aliquots of each group were transferred to Petri dishes to colony counting (CFU/mL) with the data transformed in log10. The results were submitted to ANOVA and Tukey test at 5%. RESULTS: PDT group presented total eradication of microorganisms showing statistical difference with all the other groups (5.82log reduction?99%). CONCLUSION: The high potency photopolymerizer in pulsed emission at an extra short irradiation and low concentration of rose bengal could be considered as a progressive alternative to the control of S. mutans suspensions. PMID- 27179711 TI - Antimicrobial photodynamic therapy on Candida albicans pre-treated by fluconazole delayed yeast inactivation. AB - Antimicrobial photodynamic therapy (APDI) has been used to treat localized infection and the aim of this study was to evaluate the effect of APDI combined with fluconazole in suspension of Candida albicans. C. albicans ATCC90028 was subcultured onto Sabouraud agar and inocula were prepared at yeast density of 1*10(6)CFU/mL. Methylene blue (MB) was used with concentration of 100mM. Yeast cells were incubated for 30min in 24-well plate and then irradiated by LED (660nm; 690mW; A=2.7cm(2); I=250mW/cm(2)) with radiant exposure of 30, 60, and 120J/cm(2). The same APDI setup was used with 2h fluconazole (0.5MUg/mL) incubation. A UV-vis optical absorption spectroscopy was achieved following fractionated irradiation up to 960s. There were substantial differences in the killing effect following MB-mediated APDI and C. albicans was eradicated in the both APDI groups. The fluconazole combined to APDI delayed the complete inactivation of the yeast (p<0.05). Spectroscopy showed a decrease in absorption following irradiation for all absorption peaks. APDI presented an antagonist effect in the presence of fluconazole. PMID- 27179713 TI - Autism spectrum disorder phenotype and intellectual disability in females with epilepsy and PCDH-19 mutations. AB - INTRODUCTION: Autism features and various degrees of cognitive deficit are reported in patients with PCDH-19 mutations and epilepsy. Autism spectrum disorder (ASD) and, often, cognitive profile are usually assessed clinically. We studied autism phenotype and cognitive outcome in a series of patients using standardized tools for development and ASD. We aimed to describe the phenotype of ASD in this series and to understand whether ASD is strictly linked to intellectual disability (ID) or is present as a comorbidity. METHODS: Eight females aged 5 to 17years old with PCDH-19 mutations and epilepsy were recruited. For ASD diagnosis, the Autism Diagnostic Interview - Revised (ADI-R) and the Autism Diagnosis Observation Schedule (ADOS) were administered. Patients underwent a neuropsychological examination with tests measuring global intellectual efficiency (WPPSI-III and WISC-IV), language, and executive and social cognition abilities. Parental adaptive behavioral questionnaires were also obtained (VABS, CBCL, and BRIEF). RESULTS: Six out of eight patients presented with ASD and ID. Two patients had neither ASD nor ID, and both had the latest age of onset for their epilepsy. All cognitive functions were deficient, but theory of-mind abilities compared to other cognitive features were even impaired. Features of ASD lacked major repetitive and stereotyped behaviors and show some differences with the classical ASD features related to ID. CONCLUSION: Our results show a large spectrum of ID and a very high rate of ASD in patients with epilepsy and PCDH-19 mutations. Autism spectrum disorder seems to be a genuine comorbidity, more than a consequence of ID. It highlights the importance of standardized psychiatric and cognitive evaluation in order to establish a tailored rehabilitation program. PMID- 27179714 TI - Auditory temporal processing in patients with temporal lobe epilepsy. AB - OBJECTIVE: Auditory temporal processing is the main feature of speech processing ability. Patients with temporal lobe epilepsy, despite their normal hearing sensitivity, may present speech recognition disorders. The present study was carried out to evaluate the auditory temporal processing in patients with unilateral TLE. MATERIALS AND METHODS: The present study was carried out on 25 patients with epilepsy: 11 patients with right temporal lobe epilepsy and 14 with left temporal lobe epilepsy with a mean age of 31.1years and 18 control participants with a mean age of 29.4years. The two experimental and control groups were evaluated via gap-in-noise and duration pattern sequence tests. One way ANOVA was run to analyze the data. RESULTS: The mean of the threshold of the GIN test in the control group was observed to be better than that in participants with LTLE and RTLE. Also, it was observed that the percentage of correct responses on the DPS test in the control group and in participants with RTLE was better than that in participants with LTLE. CONCLUSION: Patients with TLE have difficulties in temporal processing. Difficulties are more significant in patients with LTLE, likely because the left temporal lobe is specialized for the processing of temporal information. PMID- 27179715 TI - The challenge of establishing a correct serum potassium cutoff for inhospital triage after avalanche-induced cardiac arrest. PMID- 27179716 TI - Sodium bicarbonate dilemma in patients with out-of-hospital cardiac arrest: A double-edged sword. PMID- 27179712 TI - Clinical significance of microRNAs in chronic and acute human leukemia. AB - Small non-coding microRNAs (miRNAs) are epigenetic regulators that target specific cellular mRNA to modulate gene expression patterns and cellular signaling pathways. miRNAs are involved in a wide range of biological processes and are frequently deregulated in human cancers. Numerous miRNAs promote tumorigenesis and cancer progression by enhancing tumor growth, angiogenesis, invasion and immune evasion, while others have tumor suppressive effects (Hayes, et al., Trends Mol Med 20(8): 460-9, 2014; Stahlhut and Slack, Genome Med 5 (12): 111, 2013). The expression profile of cancer miRNAs can be used to predict patient prognosis and clinical response to treatment (Bouchie, Nat Biotechnol 31(7): 577, 2013). The majority of miRNAs are intracellular localized, however circulating miRNAs have been detected in various body fluids and represent new biomarkers of solid and hematologic cancers (Fabris and Calin, Mol Oncol 10(3):503-8, 2016; Allegra, et al., Int J Oncol 41(6): 1897-912, 2012). This review describes the clinical relevance of miRNAs, lncRNAs and snoRNAs in the diagnosis, prognosis and treatment response in patients with chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML) and acute adult T-cell leukemia (ATL). PMID- 27179717 TI - The serum brain-derived neurotrophic factor concentration prior to initiation of an in vitro fertilization cycle predicts outcome. AB - Our objective was to determine if the concentration of circulating brain-derived neurotrophic factor (BDNF) prior to cycle initiation predicts outcome in women undergoing in vitro fertilization (IVF). Stored serum samples from 226 women - 54 with a live birth, 45 with a spontaneous abortion, 38 with a biochemical pregnancy, 54 who did not become pregnant and 35 with an ectopic pregnancy- were retrospectively blindly tested for BDNF by ELISA. The median serum concentration of BDNF was highest in women with an extrauterine ectopic pregnancy (7.3ng/ml), intermediate in women whose embryos did not implant (5.5ng/ml) and lowest in women with a spontaneous abortion (4.2ng/ml), biochemical pregnancy (3.8ng/ml) or a live birth (3.6ng/ml) (P<0.0001). Among women with a positive pregnancy test an elevated BDNF level predicted an ectopic pregnancy with a sensitivity of 0.853 (0.689, 0.950) and a specificity of 0.949 (0.897, 0.979). We conclude that elevated BDNF in serum obtained before IVF cycle initiation is predictive of an extrauterine pregnancy. PMID- 27179718 TI - Comparison of performance on Hospital Compare process measures and patient outcomes between hospitals that do and do not participate in Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With The Guidelines. AB - BACKGROUND: Acute Coronary Treatment and Intervention Outcomes Network Registry Get With The Guidelines (ACTION Registry-GWTG) was designed to measure and improve the treatment and outcomes of patients with acute myocardial infarction (AMI), yet it is unknown whether performance of Medicare Hospital Compare metrics and outcomes differ between hospitals participating versus those not participating in the registry. METHODS: Using 2007 to 2010 Hospital Compare data, we matched participating to nonparticipating hospitals based on teaching status, size, percutaneous coronary intervention capability, and baseline (2007) Hospital Compare AMI process measure performance. We used linear mixed modeling to compare 2010 Hospital Compare process measure adherence, 30-day risk-adjusted mortality, and readmission rates. We repeated these analyses after stratification according to baseline performance level. RESULTS: Compared with nonparticipating hospitals, those participating were larger (median 288 vs 139 beds, P < .0001), more often teaching hospitals (18.8% vs 6.3%, P < .0001), and more likely had interventional catheterization lab capabilities (85.7% vs 34.0%, P < .0001). Among 502 matched pairs of participating and nonparticipating hospitals, we found high levels of process measure adherence in both 2007 and 2010, with minimal differences between them. Rates of 30-day mortality and readmission in 2010 were also similar between both groups. Results were consistent across strata of baseline performance level. CONCLUSIONS: In this observational analysis, there were no significant differences in the performance of Hospital Compare process measures or outcomes between hospitals in Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With The Guidelines and other hospitals not in the registry. However, baseline performance on the Hospital Compare process measures was very high in both groups, suggesting the need for new quality improvement foci to further improve patient outcomes. PMID- 27179720 TI - Ischemic cardiac outcomes and hospitalizations according to prior macrovascular disease status in patients with type 2 diabetes and recent acute coronary syndrome from the Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care trial. AB - BACKGROUND: Concerns raised regarding adverse cardiovascular (CV) outcomes with new therapies for type 2 diabetes mellitus (T2DM) have led to several large-scale CV outcome trials. The EXAMINE trial confirmed noninferiority of the dipeptidyl dipeptidase 4 inhibitor alogliptin to placebo on major adverse cardiac event rates in a post-acute coronary syndrome (ACS) T2DM population. We present data on additional ischemic cardiac events and CV hospitalizations in EXAMINE. METHODS: Patients with T2DM and an ACS event in the previous 15 to 90 days were randomly assigned to alogliptin or placebo on a background of standard treatment for diabetes. The incident rates of a 5-component composite end point of CV death, stroke, myocardial infarction, unstable angina, and coronary revascularization as well as CV hospitalization were calculated in all participants and according to macrovascular disease at baseline. RESULTS: There were no significant differences between alogliptin (n = 2,701) and placebo (n = 2,679) in the event rate of the 5 component composite endpoint with median follow-up 533 days (21.0% vs 21.5%, hazard ratio [HR] 0.98 [0.87-1.10], P = .72). No differences were observed in terms of CV hospitalization (25.0% vs 25.4%, HR 0.98 [0.88-1.09], P = .70) or coronary revascularization (10.6% vs 10.2%, HR 1.05 [0.88-1.09], P = .60). No interactions were observed for treatment and prior macrovascular disease. CONCLUSIONS: EXAMINE demonstrates that there was no increase in the risk of cardiac ischemic events and CV hospitalizations with alogliptin in a high-risk post-ACS patient population. Because these are major driver of overall health care costs, these data suggest that there would be no adverse impact on health care resource utilization. PMID- 27179719 TI - Impact of genetic variants on the upstream efficacy of renin-angiotensin system inhibitors for the prevention of atrial fibrillation. AB - BACKGROUND: Renin-angiotensin system (RAS) inhibition via angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers may reduce the risk of developing atrial fibrillation (AF) in certain populations, but the evidence is conflicting. Recent genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) associated with AF, potentially identifying clinically relevant subtypes of the disease. We sought to investigate the impact of carrier status of 9 AF-associated SNPs on the efficacy of RAS inhibition for the primary prevention of AF. METHODS: We performed SNP-RAS inhibitor interaction testing with unadjusted and adjusted Cox proportional hazards models using a discovery (Cardiovascular Health Study) and a replication (Atherosclerosis Risk in Communities) cohort. Additive genetic models were used for the SNP analyses, and 2-tailed P values <.05 were considered statistically significant. RESULTS: Among 2,796 Cardiovascular Health Study participants, none of the 9 a priori identified candidate SNPs exhibited a significant SNP-drug interaction. Two of the 9 SNPs, rs2106261 (16q22) and rs6666258 (1q21), revealed interaction relationships that neared statistical significance (with point estimates in the same direction for angiotensin-converting enzyme inhibitor only and angiotensin II receptor blocker only analyses), but neither association could be replicated among 8,604 participants in Atherosclerosis Risk in Communities. CONCLUSIONS: Our study failed to identify AF-associated SNP genetic subtypes of AF that derive increased benefit from upstream RAS inhibition for AF prevention. Future studies should continue to investigate the impact of genotype on the response to AF treatment strategies in an effort to develop personalized approaches to therapy and prevention. PMID- 27179721 TI - Family history of atrial fibrillation is associated with earlier-onset and more symptomatic atrial fibrillation: Results from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry. AB - BACKGROUND: We addressed whether patients with a family history of atrial fibrillation (AF) were diagnosed as having AF earlier in life, were more symptomatic, and had worse outcomes compared with those without a family history of AF. METHODS: Using the ORBIT-AF, we compared symptoms and disease characteristics in those with and without a family history of AF. A family history of AF was defined as AF in a first-degree family member and obtained by patient self-reporting. Multivariable Cox proportional hazard analyses were performed to compare the incidence of cardiovascular outcomes, AF progression, all-cause hospitalization, and all-cause death. RESULTS: Among 9,999 patients with AF from 176 US outpatient clinics, 1,481 (14.8%) had a family history of AF. Relative to those without, those with a family history of AF developed AF 5 years earlier on average (median age 65 vs 70 years, P < .01), with less comorbidity, and had more severe AF-related symptoms. No differences were found between the 2 groups in the risk of AF progression (adjusted hazard ratio [HR] 0.98, 95% CI 0.85-1.14), stroke, non-central nervous system embolism, or transient ischemic attack (adjusted HR 0.95, 95% CI 0.67-1.34), all-cause hospitalization (adjusted HR 1.03, 95% CI 0.94-1.12), and all-cause death (adjusted HR 1.05, 95% CI 0.86 1.27). CONCLUSIONS: Patients with a family history of AF developed AF at a younger age, had less comorbidity, and were more symptomatic. Once AF developed, no significantly increased risks of AF progression and thromboembolism were associated with a family history of AF compared with no family history. PMID- 27179722 TI - Bivalirudin versus heparin in non-ST and ST-segment elevation myocardial infarction-a registry-based randomized clinical trial in the SWEDEHEART registry (the VALIDATE-SWEDEHEART trial). AB - BACKGROUND: The optimal anticoagulant for patients with acute coronary syndrome treated with percutaneous coronary intervention (PCI) has not been validated in current practice of radial approach and pretreatment with potent P2Y12 inhibitors. Several studies have indicated increased bleeding rate and, in some instances, even increased mortality by the routine use of heparin and glycoprotein IIb/IIIa inhibitors compared to bivalirudin. Direct comparison of bivalirudin versus heparin alone has yielded contradictory results depending on study designs. METHODS/DESIGN: The VALIDATE-SWEDEHEART trial is a multicenter, prospective, randomized, registry-based, controlled, and open-label clinical trial in patients with ST-segment elevation myocardial infarction (STEMI) or non STEMI undergoing PCI pretreated with ticagrelor, prasugrel, or cangrelor. We hypothesize that bivalirudin is superior to heparin alone in reducing death, myocardial infarction, and major bleeding events at 180 days (primary end point). The trial will enroll 3,000 patients with STEMI and 3,000 patients with non-STEMI undergoing PCI. The trial will use a hybrid registry-based randomized clinical trial design where inclusion, randomization, and baseline data collection are performed using The Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies registry. The primary composite end point (death, myocardial infarction, or major bleeding events at 180 days) will be identified through active screening after 7 and 180 days and adjudicated by a blinded central end point committee. Secondary end points and long-term outcomes will be recorded from national registries. CONCLUSION: The VALIDATE-SWEDEHEART trial is founded on a nationwide clinical registry and uses a hybrid registry-based randomized clinical trial (RRCT) design methodology to evaluate efficacy and safety of bivalirudin as compared to heparin alone for acute coronary syndrome, in a large population receiving contemporary recommended therapies including predominantly radial invasive approach and pretreatment with potent P2Y12 inhibitors. PMID- 27179723 TI - Ten-year clinical outcomes after sirolimus-eluting stent implantation: Impact of an in-stent restenosis target lesion. AB - Little is known about the long-term outcomes after first-generation sirolimus eluting stent (SES) implantation. We aimed to investigate the clinical outcomes up to 10 years after SES implantation. METHODS: The study population comprised 342 patients (504 lesions) who underwent SES implantation between January 2002 and December 2004. The median duration of follow-up was 3816 days (interquartile range [Q1-Q3], 3,705-3,883 days). RESULTS: The cumulative event rate of definite stent thrombosis was 3.9%. The cumulative rate of target lesion revascularization (TLR) at 1, 5, and 10 years was 8.7%, 18.8%, and 31.1%, respectively, and the annual rate of TLR was 3.1%. Clinically driven TLR occurred at relatively constant rate during 10 years (2.0% per year). In a multivariate analysis, higher body mass index, hemodialysis, in-stent restenosis (ISR) target lesion, and total stent length >30 mm were independent risk factors of TLR within 5 years. An independent risk factor of TLR beyond 5 years was ISR target lesion. CONCLUSIONS: Late TLR after SES implantation is a long-term hazard, lasting up to 10 years. The ISR target lesion is a risk factor of TLR during 10 years. PMID- 27179724 TI - Risk and timing of recurrent ischemic events among patients with stable ischemic heart disease, non-ST-segment elevation acute coronary syndrome, and ST-segment elevation myocardial infarction. AB - BACKGROUND: We aimed to compare differences in risk and timing of recurrent ischemic events among patients with stable ischemic heart disease (SIHD), non-ST segment elevation acute coronary syndrome (NSTE-ACS), and ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). METHODS: We performed an individual data pooled analysis of 5 randomized controlled all-comer trials including a total of 8,859 patients and investigated the risk and timing of recurrent ischemic events among patients with SIHD (n = 3,543), NSTE-ACS (n = 3,364), and STEMI (n = 1,952) throughout 2 years of follow up. RESULTS: At 2 years, all-cause mortality was higher among patients with STEMI (6.4%) and NSTE-ACS (6.1%) compared with those with SIHD (4.2%) (STEMI vs SIHD: hazard ratio [HR] 1.40, 95% CI 1.09-1.78, P = .007; NSTE-ACS vs SIHD: 1.40, 95% CI 1.13-1.73, P = .002). In a landmark analysis, the risk of mortality among patients with STEMI compared with those with SIHD was confined to the first 30 days after PCI (HR 6.19, 95% CI 3.15-12.16, P < .001) but was similar between 30 days and 2 years (HR 1.00, 95% CI 0.76-1.33, P = .974) (Pinteraction < .001). Conversely, patients with NSTE-ACS had a higher risk of mortality compared with those with SIHD both within the first 30 days (HR 2.19, 95% CI 1.08-4.47, P = .031) and beyond (HR 1.34, 95% CI 1.07-1.67, P = .012) (Pinteraction < .001). A similar pattern in the differential timing of events was observed for cardiac death. Beyond 30 days, the risk of myocardial infarction was comparable in patients with STEMI and SIHD, whereas the risk in patients with NSTE-ACS was increased (HR 1.65, 95% CI 1.23-2.21, P = .001). CONCLUSION: Whereas patients with NSTE-ACS are at increased risk for death at any time after PCI, the mortality of STEMI patients is higher during the first 30 days after PCI but not thereafter compared with patients with SIHD. PMID- 27179725 TI - Changes in cardiovascular risk factors after 5 years of implementation of a population-based program to reduce cardiovascular disease: The Heart of New Ulm Project. AB - BACKGROUND: Population-based interventions aimed at reducing cardiovascular disease (CVD) hold significant potential and will be increasingly relied upon as the model for health care changes in the United States. METHODS: The Heart of New Ulm Project is a population-based project with health care, community, and workplace interventions addressing multiple levels of the social-ecological model designed to reduce modifiable CVD risk factors in rural New Ulm, MN. The community is served by one health system, enabling the use of electronic health record data for surveillance. Electronic health record data were extracted at baseline (2008-2009) and 2 follow-up periods (2010-2011, 2012-2013) for residents aged 40 to 79 years. Generalized estimating equations were used to fit longitudinal models of the risk factors. RESULTS: Of 7,855 residents in the target population, 80% had electronic health record data for each period. The prevalence of at goal (blood pressure [BP] <140/90 mm Hg) and (low-density lipoprotein cholesterol [LDL-C] <130 mg/dL) increased from 79.3% to 86.4% and 68.9% to 71.1%, respectively, from baseline to 5 years, with the largest reductions in BP and LDL-C seen in individuals not at goal at baseline. Blood pressure and lipid-lowering medication use increased from 41.8% to 44.0% and 25.3% to 29.1%, respectively. The proportion at goal for glucose increased from 46.9% to 48.2%. The prevalence body mass index <30 kg/m(2) (55%) did not change, whereas the proportion at-goal for high-density lipoprotein decreased from 63.8% to 58%, and smoking showed an increase from 11.3% to 13.6%. CONCLUSION: In a community participating in a multifaceted, population-based project aimed at reducing modifiable CVD risk factors, significant improvements in BP, LDL-C, and glucose were observed for 5 years, and body mass index remained stable in a state where obesity was increasing. PMID- 27179726 TI - Rationale and design of a home-based trial using wearable sensors to detect asymptomatic atrial fibrillation in a targeted population: The mHealth Screening To Prevent Strokes (mSToPS) trial. AB - Efficient methods for screening populations for undiagnosed atrial fibrillation (AF) are needed to reduce its associated mortality, morbidity, and costs. The use of digital technologies, including wearable sensors and large health record data sets allowing for targeted outreach toward individuals at increased risk for AF, might allow for unprecedented opportunities for effective, economical screening. The trial's primary objective is to determine, in a real-world setting, whether using wearable sensors in a risk-targeted screening population can diagnose asymptomatic AF more effectively than routine care. Additional key objectives include (1) exploring 2 rhythm-monitoring strategies-electrocardiogram-based and exploratory pulse wave-based-for detection of new AF, and (2) comparing long-term clinical and resource outcomes among groups. In all, 2,100 Aetna members will be randomized 1:1 to either immediate or delayed monitoring, in which a wearable patch will capture a single-lead electrocardiogram during the first and last 2 weeks of a 4-month period beginning immediately or 4 months after enrollment, respectively. An observational, risk factor-matched control group (n = 4,000) will be developed from members who did not receive an invitation to participate. The primary end point is the incidence of new AF in the immediate- vs delayed monitoring arms at the end of the 4-month monitoring period. Additional efficacy and safety end points will be captured at 1 and 3 years. The results of this digital medicine trial might benefit a substantial proportion of the population by helping identify and refine screening methods for undiagnosed AF. PMID- 27179727 TI - Design and rationale for the Effects of Ticagrelor and Clopidogrel in Patients with Peripheral Artery Disease (EUCLID) trial. AB - BACKGROUND: Despite overwhelming data demonstrating the efficacy of antiplatelet therapy in heart disease and stroke, data in peripheral artery disease (PAD) are less compelling. Aspirin has modest evidence supporting a reduction in cardiovascular events in patients with PAD, whereas clopidogrel monotherapy may be more effective in PAD. Ticagrelor, a potent, reversibly binding P2Y12 receptor antagonist, is beneficial in patients with acute coronary syndrome and prior myocardial infarction. The EUCLID trial is designed to address the need for effective antiplatelet therapy in PAD to decrease the risk of cardiovascular events. STUDY DESIGN: EUCLID is a randomized, double-blind, parallel-group, multinational clinical trial designed to evaluate the efficacy and safety of ticagrelor compared with clopidogrel for the prevention of major adverse cardiovascular events in subjects with symptomatic PAD. Subjects with established PAD will be randomized in a 1:1 fashion to ticagrelor 90 mg twice daily or clopidogrel 75 mg daily. The primary end point is a composite of cardiovascular death, myocardial infarction, or ischemic stroke. Other end points address limb events including acute leg ischemia, need for revascularization, disease progression by ankle-brachial index, and quality of life. The primary safety objective is Thrombolysis in Myocardial Infarction-defined major bleeding. Recruitment began in December 2012 and was completed in March 2014; 13,887 patients were randomized. The trial will continue until at least 1,364 adjudicated primary end points occur. CONCLUSIONS: The EUCLID study is investigating whether treatment with ticagrelor versus clopidogrel, given as antiplatelet monotherapy, will reduce the incidence of cardiovascular and limb specific events in patients with symptomatic PAD. PMID- 27179728 TI - Patient and physician discordance in reporting symptoms of angina among stable coronary artery disease patients: Insights from the Angina Prevalence and Provider Evaluation of Angina Relief (APPEAR) study. AB - BACKGROUND: A principal goal of treating patients with coronary artery disease (CAD) is to minimize angina and optimize quality of life. For this, physicians must accurately assess presence and frequency of patients' angina. The accuracy with which cardiologists estimate their patients' angina in contemporary, busy outpatient clinics across the United States (US) is unknown. METHODS: We enrolled patients with CAD across 25 US cardiology outpatient practices. Patients completed the Seattle Angina Questionnaire before their visit, which assessed their angina and quality of life over the prior 4 weeks. The Seattle Angina Questionnaire angina frequency domain categorized patients' angina as none, daily/weekly, or monthly. After the visit, cardiologists estimated the frequency of their patients' angina using the same categories. Kappa statistic helped to assess agreement between patient-reported and cardiologist-estimated angina. RESULTS: Among 1,257 outpatients with CAD, 67% reported no angina, 25% reported monthly angina, and 8% reported daily/weekly angina. When patients reported no angina, cardiologists accurately estimated this 93% of the time, but when patients reported monthly or daily/weekly angina symptoms, cardiologists agreed 17% and 69% of the time, respectively. Among patients with daily/weekly angina, 26% were noted as having no angina by their physicians. Agreement between patients' and cardiologists' reports (assessed by the kappa statistic) was 0.48 (95% CI 0.44-0.53), indicating moderate agreement. CONCLUSIONS: Among outpatients with stable CAD, there is substantial discordance between patient-reported and cardiologist-estimated burden of angina. Inclusion of patient-reported health status measures in routine clinical care may support better recognition of patients' symptoms by physicians. PMID- 27179729 TI - Sex-related differences in left ventricular remodeling in severe aortic stenosis and reverse remodeling after aortic valve replacement: A cardiovascular magnetic resonance study. AB - BACKGROUND: Cardiac adaptation to aortic stenosis (AS) appears to differ according to sex, but reverse remodeling after aortic valve replacement has not been extensively described. The aim of the study was to determine using cardiac magnetic resonance imaging whether any sex-related differences exist in AS in terms of left ventricular (LV) remodeling, myocardial fibrosis, and reverse remodeling after valve replacement. METHODS: One hundred patients (men, n = 60) with severe AS undergoing either transcatheter or surgical aortic valve replacement underwent cardiac magnetic resonance scans at baseline and 6 months after valve replacement. RESULTS: Despite similar baseline comorbidity and severity of AS, women had a lower indexed LV mass than did men (65.3 +/- 18.4 vs 81.5 +/- 21.3 g/m(2), P < .001) and a smaller indexed LV end-diastolic volume (87.3 +/- 17.5 vs 101.2 +/- 28.6 mL/m(2), P = .002) with a similar LV ejection fraction (58.6% +/- 10.2% vs 54.8% +/- 12.9%, P = .178). Total myocardial fibrosis mass was similar between sexes (2.3 +/- 4.1 vs 1.3 +/- 1.1 g, P = .714), albeit with a differing distribution according to sex. After aortic valve replacement, men had more absolute LV mass regression than did women (18.3 +/- 10.6 vs 12.7 +/- 8.8 g/m(2), P = .007). When expressed as a percentage reduction of baseline indexed LV mass, mass regression was similar between the sexes (men 21.7% +/- 10.1% vs women 18.4% +/- 11.0%, P = .121). There was no sex-related difference in postprocedural LV ejection fraction or aortic regurgitation. Sex was not found to be a predictor of LV reverse remodeling on multiple regression analysis. CONCLUSIONS: There are significant differences in the way that male and female hearts adapt to AS. Six months after aortic valve replacement, there are no sex-related differences in reverse remodeling, but superior reverse remodeling in men as a result of their more adverse remodeling profile at baseline. PMID- 27179732 TI - The impact of drug shortages on patients with cardiovascular disease: causes, consequences, and a call to action. AB - Shortages of cardiovascular drugs have become increasingly common, representing an ongoing public health crisis. Given few therapeutic alternatives to many of the drugs in short supply, these shortages also pose a major challenge for cardiovascular care professionals. Although changes in the regulatory environment have led to some improvements in recent years, problems involving manufacturing processes remain the most common underlying cause. Because of the complex nature of drug shortages, sustainable solutions to prevent and mitigate them will require collaboration between regulatory agencies, drug manufacturers, and other key stakeholder groups. In this report, we describe the scope of the cardiovascular drug shortage crisis in the United States, including its underlying causes and the efforts currently being made to address it. Furthermore, we provide specific recommendations for how cardiovascular care professionals can be involved in efforts to limit the impact of drug shortages on patient care as well as policy changes aimed at preventing and mitigating them. PMID- 27179730 TI - Genetic loci associated with ideal cardiovascular health: A meta-analysis of genome-wide association studies. AB - BACKGROUND: Multiple genetic loci are associated with clinical cardiovascular (CV) disease and individual CV risk factors. Individuals with ideal levels of all major CV risk factors have very low risk for CV disease morbidity or mortality. Ideal levels of risk factors can be attained by lifestyle modifications; however, little is known about gene variants associated with ideal CV health. Our objective was to carry out a genome-wide association study on the trait. METHODS AND RESULTS: We examined 2 dichotomous phenotypes of ideal CV health-clinical (untreated cholesterol <200 mg/dL, untreated blood pressure <120/<80, not diabetic) and clinical+behavioral (clinical plus: not a current smoker, body mass index <25 kg/m(2))-among white participants aged 50+/-5 years. We performed a meta-analysis of 4 genome-wide association studies (total n=11,708) from the MESA, CARDIA, ARIC, and Framingham Heart Study cohorts. We identified a single nucleotide polymorphism (rs445925) in the APOC1/APOE region that was associated with clinical ideal CV health at genome-wide level of significance (P<2.0 * 10( 9)). The significance of this region was validated using exome chip genotyping. The association with ideal CV health was attenuated after adjusting for low density lipoprotein cholesterol. CONCLUSION: A common single-nucleotide polymorphism in the APOC1/APOE region, previously found to be associated with protective levels of cholesterol and lower CV risk, may be associated with ideal health. In future replication studies, larger sample sizes may be needed to detect loci with more modest effects on ideal CV health. In addition to the important impact of lifestyle modifications, we have identified evidence for gene variation that plays a role in ideal CV health. PMID- 27179731 TI - Impact of severe lesion calcification on clinical outcome of patients with stable angina, treated with newer generation permanent polymer-coated drug-eluting stents: A patient-level pooled analysis from TWENTE and DUTCH PEERS (TWENTE II). AB - BACKGROUND: The outcome of percutaneous coronary intervention with newer generation permanent polymer-coated drug-eluting stents (DES) in patients with severely calcified lesions is greatly unknown. We assessed the impact of severe lesion calcification on clinical outcome in patients with stable angina who underwent percutaneous coronary intervention with newer generation DES. METHODS: TWENTE and DUTCH PEERS randomized trials enrolled 1423 patients with stable angina, who were categorized into patients with versus without severe target lesion calcification. A patient-level pooled analysis assessed clinical outcome, including target vessel failure (TVF), a composite of cardiac death, target vessel-related myocardial infarction, or target vessel revascularization (TVR). RESULTS: Patients with severe calcification (n = 342) were older (66.6 +/- 9.1 vs 64.2 +/- 9.8 years, P < .001) and had more diabetes (25.7% vs 20.4%, P = .04) than other patients (n = 1081). Patients with calcified lesions had higher rates of TVF (16.4% vs 9.8%, pLogrank = .001), cardiac death (4.4% vs 1.5%, P = .03), target vessel myocardial infarction (7.6% vs 3.4%, P = .001), and definite stent thrombosis (1.8% vs 0.4%, P = .02). Multivariate analysis demonstrated that severe calcification was an independent risk factor of 2-year TVF (HR 1.42, 95% CI: 1.02-1.99, pLogrank = .04); landmark analysis showed that this was based on a difference during the first year (periprocedural: 5.8% vs. 3.1%, pLogrank = .02; first year: 7.5% vs. 3.8%, pLogrank = .007; second year: 4.1% vs. 3.3%, pLogrank = .54). CONCLUSION: In patients with stable angina, severe target lesion calcification is associated with an increased risk of adverse cardiovascular events following treatment with newer generation permanent polymer-coated DES. This increase in risk is restricted to the first year of follow-up, which is an encouraging finding. PMID- 27179733 TI - Utility of positron emission tomography for drug development for heart failure. AB - Only about 1 in 5,000 investigational agents in a preclinical stage acquires Food and Drug Administration approval. Among many reasons for this includes an inefficient transition from preclinical to clinical phases, which exponentially increase the cost and the delays the process of drug development. Positron emission tomography (PET) is a nuclear imaging technique that has been used for the diagnosis, risk stratification, and guidance of therapy. However, lately with the advance of radiochemistry and of molecular imaging technology, it became evident that PET could help novel drug development process. By using a PET radioligand to report on receptor occupancy during novel agent therapy, it may help assess the effectiveness, efficacy, and safety of such a new medication in an early preclinical stage and help design successful clinical trials even at a later phase. In this article, we explore the potential implications of PET in the development of new heart failure therapies and review PET's application in the respective pathophysiologic pathways such as myocardial perfusion, metabolism, innervation, inflammation, apoptosis, and cardiac remodeling. PMID- 27179734 TI - Association between publication of appropriate use criteria and the temporal trends in diagnostic angiography in stable coronary artery disease: A population based study. AB - BACKGROUND: The appropriate use criteria (AUC) were developed to aid clinicians in making clinical decisions regarding coronary angiography. The aim of the present study was to evaluate the association between the publication of the AUC criteria in diagnostic angiography and rates of angiography in Ontario. METHODS: Our cohort consisted of all patients who underwent coronary angiography in Ontario from 1st October 2008 to 31st October 2013 for the indication of suspected stable coronary artery disease. We determined monthly age- and sex standardized rates of angiography per 100,000 adults. To determine the association between the publication of the AUC for diagnostic angiograms and the rates of angiography, we conducted a time series analysis using an autoregressive integrated moving average model. As a sensitivity analyses, we evaluated the impact of the AUC on the rates of percutaneous coronary intervention (PCI) per 100 angiograms. RESULTS: We included 114,551 angiograms for stable coronary artery disease. In the period prior to the publication of the AUC, the average monthly age- and sex-standardized rate of angiography was 18.7 per 100,000; post AUC, the average monthly rate decreased to 17.6 per 100,000 adults (P = .037). In contrast, in the 29,358 PCIs included in the analysis, the monthly PCI rates per 100 angiograms were unchanged (25.2 pre-AUC; 26.8 post-AUC; P = .29). In the sensitivity analysis, the rate of appropriate/inappropriate and uncertain indication did not significantly change over the study period. CONCLUSIONS: The publication of the diagnostic angiography AUC criteria was associated with a decrease in the population rates of diagnostic angiography. This suggests that the AUC potentially was associated with an increased threshold to pursue invasive diagnostic testing. PMID- 27179735 TI - The optimal definition of contrast-induced acute kidney injury for prediction of inpatient mortality in patients undergoing percutaneous coronary interventions. AB - BACKGROUND: It is unknown which definition of contrast-induced acute kidney injury (CI-AKI) in the setting of percutaneous coronary interventions is best associated with inpatient mortality and whether this association is stable across patients with various preprocedural serum creatinine (SCr) values. METHODS: We applied logistic regression models to multiple CI-AKI definitions used by the Kidney Disease Improving Global Outcomes guidelines and previously published studies to examine the impact of preprocedural SCr on a candidate definition's correlation with the adverse outcome of inpatient mortality. We used likelihood ratio tests to examine candidate definitions and identify those where association with inpatient mortality remained constant regardless of preprocedural SCr. These definitions were assessed for specificity, sensitivity, and positive and negative predictive values to identify an optimal definition. RESULTS: Our study cohort included 119,554 patients who underwent percutaneous coronary intervention in Michigan between 2010 and 2014. Most commonly used definitions were not associated with inpatient mortality in a constant fashion across various preprocedural SCr values. Of the 266 candidate definitions examined, 16 definition's association with inpatient mortality was not significantly altered by preprocedural SCr. Contrast-induced acute kidney injury defined as an absolute increase of SCr >=0.3 mg/dL and a relative SCr increase >=50% was selected as the optimal candidate using Perkins and Shisterman decision theoretic optimality criteria and was highly predictive of and specific for inpatient mortality. CONCLUSIONS: We identified the optimal definition for CI-AKI to be an absolute increase in SCr >=0.3 mg/dL and a relative SCr increase >=50%. Further work is needed to validate this definition in independent studies and to establish its utility for clinical trials and quality improvement efforts. PMID- 27179736 TI - Prior bleeding, future bleeding and stroke risk with oral anticoagulation in atrial fibrillation: What new lessons can ARISTOTLE teach us? PMID- 27179737 TI - Hospital triage of acute myocardial infarction: Is admission to the coronary care unit still necessary? PMID- 27179738 TI - History of bleeding and outcomes with apixaban versus warfarin in patients with atrial fibrillation in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial. AB - AIMS: History of bleeding strongly influences decisions for anticoagulation in atrial fibrillation (AF). We analyzed outcomes in relation to history of bleeding and randomization in ARISTOTLE trial patients. METHODS AND RESULTS: The on treatment safety population included 18,140 patients receiving at least 1 dose of study drug (apixaban) or warfarin. Centrally adjudicated outcomes in relation to bleeding history were analyzed using a Cox proportional hazards model adjusted for randomized treatment and established risk factors. Efficacy end points were analyzed on the randomized (intention to treat) population. A bleeding history was reported at baseline in 3,033 patients (16.7%), who more often were male, with a history of prior stroke/transient ischemic attack/systemic embolism and diabetes; higher CHADS2 scores, age, and body weight; and lower creatinine clearance and mean systolic blood pressure. Major (but not intracranial) bleeding occurred more frequently in patients with versus without a history of bleeding (adjusted hazard ratio 1.35, 95% CI 1.14-1.61). There were no significant interactions between bleeding history and treatment for stroke/systemic embolism, hemorrhagic stroke, death, or major bleeding, with fewer outcomes with apixaban versus warfarin for all of these outcomes independent of the presence/absence of a bleeding history. CONCLUSION: In patients with AF in a randomized clinical trial of oral anticoagulants, a history of bleeding is associated with several risk factors for stroke and portends a higher risk of major-but not intracranial bleeding, during anticoagulation. However, the beneficial effects of apixaban over warfarin for stroke, hemorrhagic stroke, death, or major bleeding remains consistent regardless of history of bleeding. PMID- 27179739 TI - Do stable non-ST-segment elevation acute coronary syndromes require admission to coronary care units? AB - BACKGROUND: Clinical practice guidelines recommend admitting patients with stable non-ST-segment elevation acute coronary syndrome (NSTE ACS) to telemetry units, yet up to two-thirds of patients are admitted to higher-acuity critical care units (CCUs). The outcomes of patients with stable NSTE ACS initially admitted to a CCU vs a cardiology ward with telemetry have not been described. METHODS: We used population-based data of 7,869 patients hospitalized with NSTE ACS admitted to hospitals in Alberta, Canada, between April 1, 2007, and March 31, 2013. We compared outcomes among patients initially admitted to a CCU (n=5,141) with those admitted to cardiology telemetry wards (n=2,728). RESULTS: Patients admitted to cardiology telemetry wards were older (median 69 vs 65years, P<.001) and more likely to be female (37.2% vs 32.1%, P<.001) and have a prior myocardial infarction (14.3% vs 11.5%, P<.001) compared with patients admitted to a CCU. Patients admitted directly to cardiology telemetry wards had similar hospital stays (6.2 vs 5.7days, P=.29) and fewer cardiac procedures (40.3% vs 48.5%, P<.001) compared with patients initially admitted to CCUs. There were no differences in the frequency of in-hospital mortality (1.3% vs 1.2%, adjusted odds ratio [aOR] 1.57, 95% CI 0.98-2.52), cardiac arrest (0.7% vs 0.9%, aOR 1.37, 95% CI 0.94-2.00), 30-day all-cause mortality (1.6% vs 1.5%, aOR 1.50, 95% CI 0.82-2.75), or 30-day all-cause postdischarge readmission (10.6% vs 10.8%, aOR 1.07, 95% CI 0.90-1.28) between cardiology telemetry ward and CCU patients. Results were similar across low-, intermediate-, and high-risk Duke Jeopardy Scores, and in patients with non-ST-segment myocardial infarction or unstable angina. CONCLUSIONS: There were no differences in clinical outcomes observed between patients with NSTE ACS initially admitted to a ward or a CCU. These findings suggest that stable NSTE ACS may be managed appropriately on telemetry wards and presents an opportunity to reduce hospital costs and critical care capacity strain. PMID- 27179740 TI - The China Acute Myocardial Infarction (CAMI) Registry: A national long-term registry-research-education integrated platform for exploring acute myocardial infarction in China. AB - BACKGROUND: Acute myocardial infarction (AMI) has become a major cause of hospitalization and mortality in China. There has been limited data to date available to characterize AMI presentation, contemporary patterns of medical care, and outcomes in China. AIMS: The CAMI Registry is a national project with the objectives to timely obtain real-world knowledge about AMI patients and to provide the platform for clinical research, guide preventive measures and care quality improvement efforts in China. METHODS AND PROGRESS: The CAMI registry is a prospective, nationwide, multicenter observational study for AMI patients. The registry includes three levels of hospitals (representing typical Chinese governmental and administrative models) from all provinces and municipalities throughout Mainland China except Hong Kong and Macau. Sites were instructed to enroll consecutive patients with a primary diagnosis of AMI. Clinical data, treatments, outcomes and cost are collected by local investigators and captured electronically, with a standardized set of variables and standard definitions, and rigorous data quality control. Post-discharge patient follow-up to 2 years is planned. The CAMI Registry was launched in January 2013. A total of 108 hospitals have participated in the registry so far. As of September 2014, 26,103 patients with AMI were registered. CONCLUSIONS: The CAMI registry represents a well supported and the largest national long-term registry-research-education platform for surveillance, research, prevention and care improvement for AMI in China, the world's most populous nation. The broad representation of all provinces and different-level hospitals will allow for the exploration of AMI across diverse geographic regions and economic circumstances. PMID- 27179742 TI - Directions for future trials on blood glucose-lowering drugs to improve left ventricular function post-ST-segment elevation myocardial infarction. PMID- 27179743 TI - The Dual Complexity of PTX3 in Health and Disease: A Balancing Act? AB - The humoral arm of innate immunity is complex and includes various molecules that serve as markers of inflammation with complementary characteristics, such as the short pentraxins C-reactive protein (CRP) and serum amyloid P (SAP) and the long pentraxin PTX3. There is a growing amount of evidence - including mouse and human genetics - that suggests that PTX3 is essential in conferring host resistance against selected pathogens and, moreover, that it plays a dual antagonistic role in the regulation of inflammation. Dissection of such a yin-and-yang role of pentraxins in immunity and inflammation is timely and significant as it may pave the way for better clinical exploitation against various diseases. PMID- 27179745 TI - Novel treatment strategies for smooth muscle disorders: Targeting Kv7 potassium channels. AB - Smooth muscle cells provide crucial contractile functions in visceral, vascular, and lung tissues. The contractile state of smooth muscle is largely determined by their electrical excitability, which is in turn influenced by the activity of potassium channels. The activity of potassium channels sustains smooth muscle cell membrane hyperpolarization, reducing cellular excitability and thereby promoting smooth muscle relaxation. Research over the past decade has indicated an important role for Kv7 (KCNQ) voltage-gated potassium channels in the regulation of the excitability of smooth muscle cells. Expression of multiple Kv7 channel subtypes has been demonstrated in smooth muscle cells from viscera (gastrointestinal, bladder, myometrial), from the systemic and pulmonary vasculature, and from the airways of the lung, from multiple species, including humans. A number of clinically used drugs, some of which were developed to target Kv7 channels in other tissues, have been found to exert robust effects on smooth muscle Kv7 channels. Functional studies have indicated that Kv7 channel activators and inhibitors have the ability to relax and contact smooth muscle preparations, respectively, suggesting a wide range of novel applications for the pharmacological tool set. This review summarizes recent findings regarding the physiological functions of Kv7 channels in smooth muscle, and highlights potential therapeutic applications based on pharmacological targeting of smooth muscle Kv7 channels throughout the body. PMID- 27179746 TI - Role of the EZH2 histone methyltransferase as a therapeutic target in cancer. AB - Besides being a genetic disease, cancer is also an epigenetic disease. The histone methyltransferase EZH2 is the catalytic subunit of PRC2, a highly conserved protein complex that regulates gene expression by methylating lysine 27 on histone H3. Given its role in tumorigenesis and its prognostic value in several tumor types, this protein appears a relevant therapeutic target. This review focuses on the preclinical and preliminary clinical results of studies investigating EZH2 inhibitors in human malignancies. These emerging data suggest that EZH2 inhibitors represent a very promising class of drugs, which will probably have a major impact on improving outcome and reducing toxicity for patients with indolent and aggressive B-cell lymphomas and other specific solid tumors. PMID- 27179747 TI - Imaging and 1-day kinetics of intracoronary stem cell transplantation in patients with idiopathic dilated cardiomyopathy. AB - BACKGROUND: Stem cell transplantation is an emerging method of treatment for patients with cardiovascular disease. There are few studies completed or ongoing on stem cell therapy in patients with idiopathic dilated cardiomyopathy (IDCM). Information on stem cell homing and distribution in the myocardium after transplantation might provide important insight into effectiveness of transplantation procedure. AIM: To assess early engraftment, retention and migration of intracoronarily transplanted stem cells in the myocardium of patients with advanced dilated cardiomyopathy of non-ischaemic origin using stem cell labeling with (99m)Tc-exametazime (HMPAO). MATERIALS, METHODS: Thirty-five patients with IDCM and advanced heart failure were included in the study. Autologous hematopoietic (CD34+) stem cells were harvested by peripheral blood apheresis after bone marrow stimulation, labeled with (99m)Tc-HMPAO, tested for viability and injected into coronary vessel supplying areas of myocardium selected by myocardial perfusion scintigraphy as dysfunctional yet viable. Imaging was performed 1h and 18h after transplantation. RESULTS: Myocardial stem cell retention ranged from 0 to 1.44% on early and 0-0.97% on delayed imaging. Significant efflux of stem cells occurred from site of delivery in this time period (p<0.001). Stem cell viability was not affected by labeling. CONCLUSION: Stem cell labeling with (99m)Tc-HMPAO is a feasible method for stem cell tracking after transplantation in patients with IDCM. PMID- 27179741 TI - Corrigendum to 'The Brazilian Cardioprotective Nutritional Program to reduce events and risk factors in secondary prevention for cardiovascular disease: study protocol (The BALANCE Program Trial)' [American Heart Journal 171/1 (2016) 73 81]. PMID- 27179744 TI - Multifunctional roles of PKCdelta: Opportunities for targeted therapy in human disease. AB - The serine-threonine protein kinase, protein kinase C-delta (PKCdelta), is emerging as a bi-functional regulator of cell death and proliferation. Studies in PKCdelta-/- mice have confirmed a pro-apoptotic role for this kinase in response to DNA damage and a tumor promoter role in some oncogenic contexts. In non transformed cells, inhibition of PKCdelta suppresses the release of cytochrome c and caspase activation, indicating a function upstream of apoptotic pathways. Data from PKCdelta-/- mice demonstrate a role for PKCdelta in the execution of DNA damage-induced and physiologic apoptosis. This has led to the important finding that inhibitors of PKCdelta can be used therapeutically to reduce irradiation and chemotherapy-induced toxicity. By contrast, PKCdelta is a tumor promoter in mouse models of mammary gland and lung cancer, and increased PKCdelta expression is a negative prognostic indicator in Her2+ and other subtypes of human breast cancer. Understanding how these distinct functions of PKCdelta are regulated is critical for the design of therapeutics to target this pathway. This review will discuss what is currently known about biological roles of PKCdelta and prospects for targeting PKCdelta in human disease. PMID- 27179749 TI - Osteoarthritis and mortality: A prospective cohort study and systematic review with meta-analysis. AB - OBJECTIVES: Osteoarthritis (OA) is a leading cause of disability, but the relationship with premature mortality remains uncertain. We aimed to investigate the relationship between OA and mortality from any cause and from cardiovascular disease (CVD). METHODS: Electronic literature databases searches were conducted to identify prospective studies comparing mortality in a sample of people with and without OA. Risk of all-cause and CVD mortality were summarized using adjusted hazard ratios (HRs) for joint specific (hand, hip, and knee) and joint non-specific OA. New data from the Progetto Veneto Anziani (PRO.V.A.) study were also included. RESULTS: From the PRO.V.A. study (N = 2927), there was no significant increase in mortality risk for participants with any joint OA (N = 1858) compared to non-OA (all-cause, HR = 0.95, 95% CI: 0.77-1.15 and CVD, HR = 1.12, 95% CI: 0.82-1.54). On meta-analysis, seven studies (OA = 10,018/non-OA = 18,541), with a median 12-year follow-up, reported no increased risk of any-cause mortality in those with OA (HR = 1.10, 95% CI: 0.97-1.25). After removing data on hand OA, a significant association between OA and mortality was observed (HR = 1.18, 95% CI: 1.08-1.28). There was a significant higher risk of overall mortality for (1) studies conducted in Europe, (2) patients with multi-joint OA; and (3) a radiological diagnosis of OA. OA was associated with significantly higher CVD mortality (HR = 1.21, 95% CI: 1.10-1.34). CONCLUSIONS: People with OA are at increased risk of death due to CVD. The relationship with overall mortality is less clear and may be moderated by the presence of hand OA. PMID- 27179748 TI - Radiolabeled hydroxamate-based matrix metalloproteinase inhibitors: How chemical modifications affect pharmacokinetics and metabolic stability. AB - INTRODUCTION: Dysregulated MMP expression or activation is associated with several diseases. To study MMP activity in vivo by means of PET a radiolabeled MMP inhibitor (MMPI) functioning as radiotracer has been developed by our group based on the lead structure CGS 25966. MATERIALS AND METHODS: Aiming at the modification of the pharmacokinetics of this lipophilic model tracer a new class of MMPIs has been discovered, consisting of additional fluorinated hydrophilic substructures, such as mini-PEG and/or 1,2,3-triazole units. To identify the best candidate for further clinical applications, radiofluorinated compounds of each subgroup have been (radio) synthesized and evaluated regarding their biodistribution behavior and their metabolic stability. RESULTS: Radiosyntheses of different triazole based MMPIs could be realized using two step "click chemistry" procedures. Compared to lead structure [(18)F]FEtO-CGS 25966 ([(18)F]1e, log D(exp) =2.02, IC50=2-50nM) all selected candidates showed increased hydrophilicities and inhibition potencies (log D(exp) =0.23-1.25, IC50=0.006-6nM). Interestingly, despite different hydrophilicities most triazole based MMPIs showed no significant differences in their in vivo biodistribution behavior and were cleared predominantly via the hepatobiliary excretion route. Biostability and metabolism studies in vitro and in vivo revealed significant higher metabolic stability for the triazole moiety compared to the benzyl ring in the lead structure. Cleavage of ethylene glycol subunits of the mini-PEG chain led to a faster metabolism of mini-PEG containing MMPIs. CONCLUSION: The introduction of hydrophilic groups such as mini-PEG and 1,2,3-triazole units did not lead to a significant shift of the hepatobiliary elimination towards renal clearance. Particularly the introduction of mini-PEG chains led to an intense metabolic decomposition. Substitution of the benzyl moiety in lead structure 1e by a 1,2,3-trizole ring resulted in an increased metabolic stability. Therefore, the 1,2,3-triazole-1-yl-methyl substituted MMPI [(18)F]3a was found to be the most stable candidate in this series and should be chosen for further preclinical evaluation. PMID- 27179750 TI - High absolute risk of severe infections among Indigenous adults in rural northern Australia is amplified by diabetes - A 7 year follow up study. AB - AIMS: To quantify the risk of hospitalization for infections in Indigenous Australian adults with diabetes in rural and remote communities. METHODS: 2787 Indigenous adults including 396 with diabetes at baseline from 19 communities in North Queensland from 1998 to 2007 were included in the study. Main measures were weight, height, waist circumference, blood pressure, fasting glucose, lipids, self-reported tobacco smoking, alcohol intake and physical activity. Baseline data were linked to hospital separation data using probabilistic linkage. The association between diabetes and hospitalization for all causes and infections was investigated using generalized linear model (GLM) and adjusted for other baseline measurements. RESULTS: During a median follow up of 7years, 461 participants were hospitalized with 762 episodes of infection. 277 patients with diabetes (70%) were hospitalized at least once. 40% (110 in 277) were for community acquired infections. Patients with diabetes were twice as likely to be hospitalized for infections as those without diabetes (adjusted risk ratio 2.1, 95% CI 1.6-2.8), especially for urinary tract infections, cellulitis, and septicaemia. Median length of stay was 6 (IQR 3-13) days for diabetes patients compared to 3.4days (IQR 2-6.4) for those without diabetes (P<0.001) CONCLUSIONS: In addition to an already high rate of hospitalizations for infections among Indigenous compared to non-Indigenous Australians, diabetes confers an additional risk for severe infections especially urinary tract infection, cellulitis and septicaemia. Recovery is also comparatively slower. Early recognition and management of these infections in the primary care setting may reduce this risk and better control of glycaemia and its risk factors may improve underlying immune dysfunction. PMID- 27179751 TI - Stratifying cardiovascular risk in diabetes: The role of diabetes-related clinical characteristics and imaging. AB - Diabetes is a major coronary heart disease (CHD) and cardiovascular disease (CVD) risk factor and has traditionally been classified as a CHD risk equivalent. CVD risk, however, is heterogeneous among diabetic patients and thus further evaluation is warranted before initiating or titrating preventive pharmacotherapy. Prognostic clinical characteristics of diabetes such as age of onset, duration, and severity of diabetes, as well as concomitant cardiometabolic factors account for much of the variability in CHD and CVD risk. This heterogeneity can also be evaluated directly using non-invasive imaging, which allows for a more individualized risk assessment in order to minimize both under and overtreatment. In this paper, we review guideline recommendations for atherosclerotic CVD risk assessment driving the use of statins or aspirin for certain subgroups of patients with diabetes. We further discuss imaging techniques, such as stress myocardial perfusion imaging, coronary computed tomography angiography, and coronary artery calcium (CAC) scoring that can guide the decision to treat high-risk patients. Among imaging tests, current guidelines consider CAC scoring the most appropriate risk stratification tool for asymptomatic individuals with diabetes that can guide initiating/intensifying or withholding the most aggressive pharmacological therapies among high-risk (CAC>100) or low-risk (CAC=0) individuals, respectively. PMID- 27179752 TI - New ISSCR guidelines: clinical translation of stem cell research. PMID- 27179753 TI - Unmet need for abortion and woman-centered contraceptive care. PMID- 27179754 TI - Lung, e-cigarettes, and health: response from the Royal College of Physicians. PMID- 27179755 TI - Abortion incidence between 1990 and 2014: global, regional, and subregional levels and trends. AB - BACKGROUND: Information about the incidence of induced abortion is needed to motivate and inform efforts to help women avoid unintended pregnancies and to monitor progress toward that end. We estimate subregional, regional, and global levels and trends in abortion incidence for 1990 to 2014, and abortion rates in subgroups of women. We use the results to estimate the proportion of pregnancies that end in abortion and examine whether abortion rates vary in countries grouped by the legal status of abortion. METHODS: We requested abortion data from government agencies and compiled data from international sources and nationally representative studies. With data for 1069 country-years, we estimated incidence using a Bayesian hierarchical time series model whereby the overall abortion rate is a function of the modelled rates in subgroups of women of reproductive age defined by their marital status and contraceptive need and use, and the sizes of these subgroups. FINDINGS: We estimated that 35 abortions (90% uncertainty interval [UI] 33 to 44) occurred annually per 1000 women aged 15-44 years worldwide in 2010-14, which was 5 points less than 40 (39-48) in 1990-94 (90% UI for decline -11 to 0). Because of population growth, the annual number of abortions worldwide increased by 5.9 million (90% UI -1.3 to 15.4), from 50.4 million in 1990-94 (48.6 to 59.9) to 56.3 million (52.4 to 70.0) in 2010-14. In the developed world, the abortion rate declined 19 points (-26 to -14), from 46 (41 to 59) to 27 (24 to 37). In the developing world, we found a non-significant 2 point decline (90% UI -9 to 4) in the rate from 39 (37 to 47) to 37 (34 to 46). Some 25% (90% UI 23 to 29) of pregnancies ended in abortion in 2010-14. Globally, 73% (90% UI 59 to 82) of abortions were obtained by married women in 2010-14 compared with 27% (18 to 41) obtained by unmarried women. We did not observe an association between the abortion rates for 2010-14 and the grounds under which abortion is legally allowed. INTERPRETATION: Abortion rates have declined significantly since 1990 in the developed world but not in the developing world. Ensuring access to sexual and reproductive health care could help millions of women avoid unintended pregnancies and ensure access to safe abortion. FUNDING: UK Government, Dutch Ministry of Foreign Affairs, Norwegian Agency for Development Cooperation, The David and Lucile Packard Foundation, UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction. PMID- 27179756 TI - Novel dual agonist peptide analogues derived from dogfish glucagon show promising in vitro insulin releasing actions and antihyperglycaemic activity in mice. AB - The antidiabetic potential of thirteen novel dogfish glucagon derived analogues were assessed in vitro and in acute in vivo studies. Stable peptide analogues enhanced insulin secretion from BRIN-BD11 beta-cells (p < 0.001) and reduced acute glycaemic responses following intraperitoneal glucose (25 nmol/kg) in healthy NIH Swiss mice (p < 0.05-p<0.001). The in vitro insulinotropic actions of [S2a]dogfish glucagon, [S2a]dogfish glucagon-exendin-4(31-39) and [S2a]dogfish glucagon-Lys(30)-gamma-glutamyl-PAL, were blocked (p < 0.05-p<0.001) by the specific GLP-1 and glucagon receptor antagonists, exendin-4(9-39) and (desHis(1)Pro(4)Glu(9))glucagon amide but not by (Pro(3))GIP, indicating lack of GIP receptor involvement. These analogues dose-dependently stimulated cAMP production in GLP-1 and glucagon (p < 0.05-p<0.001) but not GIP-receptor transfected cells. They improved acute glycaemic and insulinotropic responses in high-fat fed diabetic mice and in wild-type C57BL/6J and GIPR-KO mice (p < 0.05 p<0.001), but not GLP-1R-KO mice, confirming action on GLP-1 but not GIP receptors. Overall, dogfish glucagon analogues have potential for diabetes therapy, exerting beneficial metabolic effects via GLP-1 and glucagon receptors. PMID- 27179757 TI - Up-regulation of Hsp27 by ERalpha/Sp1 facilitates proliferation and confers resistance to apoptosis in human papillary thyroid cancer cells. AB - 17beta-estradiol (E2) has been suggested to play a role in the development and progression of papillary thyroid cancer. Heat shock protein 27 (Hsp27) is a member of the Hsp family that is responsible for cell survival under stressful conditions. Previous studies have shown that the 5'-promoter region of Hsp27 gene contains a specificity protein-1 (Spl) and estrogen response element half-site (ERE-half), which contributes to Hsp27 induction by E2 in breast cancer cells. However, it is unclear whether Hsp27 can be up-regulated by E2 and which estrogen receptor (ER) isoform and tethered transcription factor are involved in this regulation in papillary thyroid cancer cells. In the present study, we demonstrated that Hsp27 can be effectively up-regulated by E2 at mRNA and protein levels in human K1 and BCPAP papillary thyroid cancer cells which have more than two times higher level of ERalpha than that of ERbeta. The up-regulation of Hsp27 by E2 is mediated by ERalpha/Sp1 and ERbeta has repressive effect on this ERalpha/Sp1-mediated up-regulation of Hsp27. Moreover, we showed that the up regulation of Hsp27 by ERalpha/Sp1 facilitates proliferation and confers resistance to apoptosis through interaction with procaspase-3. Targeting this pathway may be a potential strategy for therapy of papillary thyroid cancer. PMID- 27179758 TI - Network analysis of human diseases using Korean nationwide claims data. AB - OBJECTIVE: To investigate disease-disease associations by conducting a network analysis using Korean nationwide claims data. METHODS: We used the claims data from the Health Insurance Review and Assessment Service-National Patient Sample for the year 2011. Among the 2049 disease codes in the claims data, 1154 specific disease codes were used and combined into 795 representative disease codes. We analyzed for 381 representative codes, which had a prevalence of >0.1%. For disease code pairs of a combination of 381 representative disease codes, P values were calculated by using the chi(2) test and the degrees of associations were expressed as odds ratios (ORs). RESULTS: For 5515 (7.62%) statistically significant disease-disease associations with a large effect size (OR>5), we constructed a human disease network consisting of 369 nodes and 5515 edges. The human disease network shows the distribution of diseases in the disease network and the relationships between diseases or disease groups, demonstrating that diseases are associated with each other, forming a complex disease network. We reviewed 5515 disease-disease associations and classified them according to underlying mechanisms. Several disease-disease associations were identified, but the evidence of these associations is not sufficient and the mechanisms underlying these associations have not been clarified yet. Further research studies are needed to investigate these associations and their underlying mechanisms. CONCLUSION: Human disease network analysis using claims data enriches the understanding of human diseases and provides new insights into disease disease associations that can be useful in future research. PMID- 27179760 TI - Effects of aluminum on cells and tissues. PMID- 27179759 TI - Transfer of malignant trait to BRCA1 deficient human fibroblasts following exposure to serum of cancer patients. AB - BACKGROUND: It was reported that metastases might occur via transfer of biologically active blood circulating molecules from the primary tumor to distant organs rather than only migration of cancer cells. We showed in an earlier study that exposure of immortalized human embryonic kidney cells (HEK 293) to cancer patient sera, induce their transformation into undifferentiated cancers due to a horizontal transfer of malignant traits. In the present work, we tested the hypothesis that even other human cells as long as they are deficient for a single oncosuppressor gene might undergo malignant transformation when exposed to human cancer serum. METHODS: We used the CRISPR/Cas9 system to establish a stable BRCA1 knockout (KO) in human fibroblasts. The BRCA1-KO fibroblasts were exposed to cancer patients' sera or healthy patients' sera for 2 weeks. Treated cells were analyzed for cell proliferation and transformation to study their susceptibility to the oncogenic potential of cancer patients' sera and to determine the possible mechanisms underlying their hypothesized transformation. RESULTS: BRCA1-KO fibroblasts treated with cancer patients' sera displayed higher proliferation and underwent malignant transformation as opposed to wild type control fibroblasts, which were not affected by exposure to cancer patients' sera. The malignant transformation was not seen when BRCA1-KO fibroblasts were treated with healthy human sera. Histological analysis of tumors generated by BRCA1-KO fibroblasts showed that they were carcinomas with phenotypical characteristics related to the cancers of the blood donor patients. Interestingly, BRCA1-KO fibroblasts were significantly more prone to internalize serum-derived exosomes, when compared to wild type fibroblasts. This suggests that oncosuppressor genes might protect the integrity of the cell genome also by blocking integration of cancer-derived exosomes. CONCLUSION: These data support the hypothesis that any human cells carrying a single oncosuppressor mutation is capable of integrating cancer factors carried in the blood and undergo complete malignant transformation. Oncosuppressor genes might protect the cell genome by impeding the integration inside the cells of these mutating factors. PMID- 27179761 TI - Initial examination of priming tasks to decrease delay discounting. AB - Steep discounting of delayed rewards is linked with a variety of unhealthy behaviors that contribute to the major causes of preventable death and disease. Growing evidence suggests that decreases in delay discounting contribute to healthier preferences. This study sought to provide preliminary evidence for the viability of developing a brief priming task to reduce delay discounting in a large, diverse group of individuals. Participants (n=1,122) were randomized to one of three conditions: Future Focus (FF), Present Focus (PF), and Non-Temporal Focus (NTF) intended respectively to decrease, increase, or have no effect on delay discounting. Participants then completed the Monetary Choice Questionnaire, a brief assessment of delay discounting rate. Participants randomized to FF exhibited significantly lower discounting rates than those randomized to PF or NTF conditions. Race, Hispanic background, social self-monitoring, education, and cigarette smoking also accounted for a significant amount of variance in the discounting model. These findings provide support for the development of a brief priming intervention that might be examined in clinical or public health contexts to decrease discounting and support healthy choices. PMID- 27179762 TI - The clinical course of hereditary pancreatitis in children - A comprehensive analysis of 41 cases. AB - BACKGROUND: Available data from adult patients do not reflect natural course of hereditary pancreatitis (HP) in children. To date, no study has assessed the clinical course of HP in children. OBJECTIVE: To investigate the clinical course of HP in children and compare it to non-HP group with chronic pancreatitis (CP). METHODS: A group of 265 children with CP, hospitalized from 1988 to 2014, were enrolled in the study. Medical records of those patients were reviewed for data on presentation, diagnostic findings and treatment. All children were screened for mutations in major pancreatitis-associated genes, i.e. PRSS1, SPINK1, and CFTR. RESULTS: HP was diagnosed in 41 children (15.5%). Family history was positive in 88% of children with HP. Mutations of PRSS1 gene were found in 80% (33/41) of HP patients. We detected p.R122H, p.R122C, p.N29I, and p.E79K mutation in 34% (14/41), 27% (11/41), 12% (5/41), and 7% (3/41) of HP patients, respectively. Patients with paternal inheritance had first symptoms earlier than those with maternal inheritance (5.9 vs. 9.1 years; P < 0.05). Children with HP showed more severe changes in ERCP then those from non-HP group (2.05 Cambridge grade, vs. 1.6 degrees ; P < 0.05). ESWL was performed more frequently in HP group (12.2% vs. 3.1%; P < 0.05). There was no difference in age of disease onset (7.98 vs. 8.9 years; NS), pancreatic duct stenting (46.3% vs. 33%; NS), or number of surgical interventions (12.2% vs. 14.3%; NS) between both groups. CONCLUSIONS: Children with HP reveal significantly more severe clinical presentation of the disease than non-HP patients, despite the same age of onset. PMID- 27179763 TI - The importance of the Crohn's disease activity index in surgery for small bowel Crohn's disease. AB - AIM OF THE STUDY: Compared with patients with other benign intestinal conditions, patients with CD are at increased risk of developing postoperative complications following intestinal resection. We searched for useful tools for predicting postoperative complication in patients with CD by comparing the relationship between postoperative morbidity in these patients as measured by three different scoring tools: general surgical risk (POSSUM score), disease activity (CDAI), and nutritional screening (nutritional prognostic index). METHODS: We performed a retrospective review of 50 patients with small bowel CD who underwent surgical resection and primary anastomosis between 1999 and 2014. RESULTS: This study enrolled 34 men and 16 women. The mean age was 38.4 years (range: 20-81 years). There was no postoperative mortality. The overall postoperative morbidity rate (33.7%) predicted by POSSUM was similar to the rate in the study patients (36.0%). Although POSSUM score predicted higher postoperative morbidity rates in patients who underwent emergency surgery (estimated morbidity: 52.8%), the actual postoperative morbidity rate in the emergency surgery group (26.7%) was smaller than in the elective surgery group (40.0%). In addition, neither preoperative nutritional status nor POSSUM score was related to the severity of postoperative complications. CDAI score was significantly related to the severity of postoperative complications (P=0.032). CONCLUSION: Based on the above results, a high preoperative CDAI score can predict negative postoperative outcomes. We believe that disease activity should be controlled using various treatment modalities, such as enteral or total parenteral nutrition as well as medication, before performing surgery in patients with CD. PMID- 27179764 TI - Upgrading biomaterials with synthetic biological modules for advanced medical applications. AB - One key aspect of synthetic biology is the development and characterization of modular biological building blocks that can be assembled to construct integrated cell-based circuits performing computational functions. Likewise, the idea of extracting biological modules from the cellular context has led to the development of in vitro operating systems. This principle has attracted substantial interest to extend the repertoire of functional materials by connecting them with modules derived from synthetic biology. In this respect, synthetic biological switches and sensors, as well as biological targeting or structure modules, have been employed to upgrade functions of polymers and solid inorganic material. The resulting systems hold great promise for a variety of applications in diagnosis, tissue engineering, and drug delivery. This review reflects on the most recent developments and critically discusses challenges concerning in vivo functionality and tolerance that must be addressed to allow the future translation of such synthetic biology-upgraded materials from the bench to the bedside. PMID- 27179766 TI - Characterization of the fretting corrosion behavior, surface and debris from head taper interface of two different modular hip prostheses. AB - Modular hip prostheses are flexible to match anatomical variations and to optimize mechanical and tribological properties of each part by using different materials. However, micromotions associated with the modular components can lead to fretting corrosion and, consequently, to release of debris which can cause adverse local tissue reactions in human body. In the present study, the surface damage and residues released during in vitro fretting corrosion tests were characterized by stereomicroscope, SEM and EDS. Two models of modular hip prosthesis were studied: Model SS/Ti Cementless whose stem was made of ASTM F136 Ti-6Al-4V alloy and whose metallic head was made of ASTM F138 austenitic stainless steel, and Model SS/SS Cemented with both components made of ASTM F138 stainless steel. The fretting corrosion tests were evaluated according to the criteria of ASTM F1875 standard. Micromotions during the test caused mechanical wear and material loss in the head-taper interface, resulting in fretting corrosion. Model SS/SS showed higher grade of corrosion. Different morphologies of debris predominated in each model studied. Small and agglomerated particles were observed in the Model SS/Ti and irregular particles in the Model SS/SS. After 10 million cycles, the Model SS/Ti was more resistant to fretting corrosion than the Model SS/SS. PMID- 27179765 TI - The role of schools in children and young people's self-harm and suicide: systematic review and meta-ethnography of qualitative research. AB - BACKGROUND: Evidence reports that schools influence children and young people's health behaviours across a range of outcomes. However there remains limited understanding of the mechanisms through which institutional features may structure self-harm and suicide. This paper reports on a systematic review and meta-ethnography of qualitative research exploring how schools influence self harm and suicide in students. METHODS: Systematic searches were conducted of nineteen databases from inception to June 2015. English language, primary research studies, utilising any qualitative research design to report on the influence of primary or secondary educational settings (or international equivalents) on children and young people's self-harm and suicide were included. Two reviewers independently appraised studies against the inclusion criteria, assessed quality, and abstracted data. Data synthesis was conducted in adherence with Noblit and Hare's meta-ethnographic approach. Of 6744 unique articles identified, six articles reporting on five studies were included in the meta ethnography. RESULTS: Five meta-themes emerged from the studies. First, self-harm is often rendered invisible within educational settings, meaning it is not prioritised within the curriculum despite students' expressed need. Second, where self-harm transgresses institutional rules it may be treated as 'bad behaviour', meaning adequate support is denied. Third, schools' informal management strategy of escalating incidents of self-harm to external 'experts' serves to contribute to non-help seeking behaviour amongst students who desire confidential support from teachers. Fourth, anxiety and stress associated with school performance may escalate self-harm and suicide. Fifth, bullying within the school context can contribute to self-harm, whilst some young people may engage in these practices as initiation into a social group. CONCLUSIONS: Schools may influence children and young people's self-harm, although evidence of their impact on suicide remains limited. Prevention and intervention needs to acknowledge and accommodate these institutional-level factors. Studies included in this review are limited by their lack of conceptual richness, restricting the process of interpretative synthesis. Further qualitative research should focus on the continued development of theoretical and empirical insight into the relationship between institutional features and students' self-harm and suicide. PMID- 27179767 TI - Finite element analysis of a pseudoelastic compression-generating intramedullary ankle arthrodesis nail. AB - Tibio-talo-calcaneal (TTC) arthrodesis is an end-stage treatment for patients with severe degeneration of the ankle joint. This treatment consists of using an intramedullary nail (IM) to fuse the calcaneus, talus, and tibia bones together into one construct. Poor bone quality within the joint prior to surgery is common and thus the procedure has shown complications due to non-union. However, a new FDA-approved IM nail has been released that houses a nickel titanium (NiTi) rod that uses its inherent pseudoelastic material properties to apply active compression across the fusion site. Finite element analysis was performed to model the mechanical response of the NiTi within the device. A bone model was then developed based on a quantitative computed tomography (QCT) image for anatomical geometry and bone material properties. A total bone and device system was modeled to investigate the effect of bone quality change and gather load sharing properties during gait loading. It was found that during the highest magnitude loading of gait, the load taken by the bone was more than 50% higher than the load taken by the nail. When comparing the load distribution during gait, results from this study would suggest that the device helps to prevent stress shielding by allowing a more even distribution of load between bone and nail. In conditions where bone quality may vary patient-to-patient, the model indicates that a 10% decrease in overall bone modulus (i.e. material stiffness) due to reduced bone mineral density would result in higher stresses in the nail (3.4%) and a marginal decrease in stress for the bone (0.5%). The finite element model presented in this study can be used as a quantitative tool to further understand the stress environment of both bone and device for a TTC fusion. Furthermore, the methodology presented gives insight on how to computationally program and use the unique material properties of NiTi in an active compression state useful for bone fracture healing or fusion treatments. PMID- 27179768 TI - Mechanical properties, structural and texture evolution of biocompatible Ti-45Nb alloy processed by severe plastic deformation. AB - Biocompatible beta Ti-45Nb (wt%) alloys were subjected to different methods of severe plastic deformation (SPD) in order to increase the mechanical strength without increasing the low Young's modulus thus avoiding the stress shielding effect. The mechanical properties, microstructural changes and texture evolution were investigated, by means of tensile, microhardness and nanoindentation tests, as well as TEM and XRD. Significant increases of hardness and ultimate tensile strength up to a factor 1.6 and 2, respectively, could be achieved depending on the SPD method applied (hydrostatic extrusion - HE, high pressure torsion - HPT, and rolling and folding - R&F), while maintaining the considerable ductility. Due to the high content of beta-stabilizing Nb, the initial lattice structure turned out to be stable upon all of the SPD methods applied. This explains why with all SPD methods the apparent Young's modulus measured by nanoindentation did not exceed that of the non-processed material. For its variations below that level, they could be quantitatively related to changes in the SPD-induced texture, by means of calculations of the Young's modulus on basis of the texture data which were carefully measured for all different SPD techniques and strains. This is especially true for the significant decrease of Young's modulus for increasing R&F processing which is thus identified as a texture effect. Considering the mechanical biocompatibility (percentage of hardness over Young's modulus), a value of 3-4% is achieved with all the SPD routes applied which recommends them for enhancing beta Ti-alloys for biomedical applications. PMID- 27179769 TI - Biochemical and biophysical characterization of cell-free synthesized Rift Valley fever virus nucleoprotein capsids enables in vitro screening to identify novel antivirals. AB - BACKGROUND: Viral capsid assembly involves the oligomerization of the capsid nucleoprotein (NP), which is an essential step in viral replication and may represent a potential antiviral target. An in vitro transcription-translation reaction using a wheat germ (WG) extract in combination with a sandwich ELISA assay has recently been used to identify small molecules with antiviral activity against the rabies virus. RESULTS: Here, we examined the application of this system to viruses with capsids with a different structure, such as the Rift Valley fever virus (RVFV), the etiological agent of a severe emerging infectious disease. The biochemical and immunological characterization of the in vitro generated RVFV NP assembly products enabled the distinction between intermediately and highly ordered capsid structures. This distinction was used to establish a screening method for the identification of potential antiviral drugs for RVFV countermeasures. CONCLUSIONS: These results indicated that this unique analytical system, which combines nucleoprotein oligomerization with the specific immune recognition of a highly ordered capsid structure, can be extended to various viral families and used both to study the early stages of NP assembly and to assist in the identification of potential antiviral drugs in a cost-efficient manner. REVIEWERS: Reviewed by Jeffry Skolnick and Noah Isakov. For the full reviews please go to the Reviewers' comments section. PMID- 27179770 TI - The Efficacy and Safety of Combination of Intravenous and Topical Tranexamic Acid in Revision Hip Arthroplasty: A Randomized, Controlled Trial. AB - BACKGROUND: Revision total hip arthroplasty (THA) is associated with substantial blood loss and a high probability of blood transfusion in the perioperative period. This study aimed to evaluate the efficacy and safety of combination of intravenous (IV) and topical tranexamic acid (TXA) in revision THA. METHODS: Eighty-four consecutive patients undergoing revision THA were randomized into combined group and IV-TXA group. Patients in the combined group were given intravenously 15 mg/kg TXA as a preoperative, and topical TXA solution was applied at a concentration of 3 g TXA per 100-mL saline during the different procedure points. Patients in the IV-TXA group were given intravenously 15 mg/kg TXA alone. RESULTS: The mean total blood loss, drainage volume, and maximum hemoglobin drop were significantly lower in the combined group than the IV-TXA group (P < .001, P < .001, P < .001, respectively). Compared with the IV-TXA group, the amount of blood transfusions and number of blood transfusions required were decreased dramatically in the combined group (P = .027, P < .001, respectively). One deep vein thrombosis and 4 calf muscular vein thrombosis in the combined group and 3 calf muscular vein thrombosis in the IV-TXA were detected by the Doppler ultrasound. No pulmonary embolism was observed and no significant differences were found in other complications between the 2 groups. CONCLUSION: This study showed that combined administration of IV and topical TXA in revision THA can effectively decrease total blood loss and number of blood transfusions required without increasing the risk of deep vein thrombosis or/and pulmonary embolism compared with IV-TXA alone. PMID- 27179771 TI - Lingering Risk: Bariatric Surgery Before Total Knee Arthroplasty. AB - BACKGROUND: Obesity continues to increase in the United States with an estimated 35% obesity and 8% bariatric (body mass index >40) rate in adults. Bariatric patients seek advice from arthroplasty surgeons regarding the temporality of bariatric surgery (BS), yet no consensus currently exists in the literature. METHODS: A total of 39,014 patients were identified in a claim-based review of the entire Medicare database with International Classification of Diseases, Ninth Revision codes to identify patients in 3 groups. Patients who underwent BS before total knee arthroplasty (group I: 5914 experimental group) and 2 control groups that did not undergo BS but had either a body mass index >40 (group II: 6480 bariatric control) or <25 (group III: 26,616 normal weight control). International Classification of Diseases, Ninth Revision, Clinical Modification codes identified preoperative demographics or comorbidities and evaluated short term medical (30 day) and long-term surgical (90 days and 2 years) complications. RESULTS: Group I had the greatest female predominance, youngest age, and highest incidence of: deficiency anemia, cardiovascular disease, pulmonary disease, liver disease, ulcer disease, polysubstance abuse, psychiatric disorders, and smoking. Medical and surgical complication incidences were greatest in group I including: 4.98% deep vein thrombosis; 5.31% pneumonia; 10.09% heart failure; and 2-year infection, revision, and manipulation rates of 5.8%, 7.38%, and 3.13%, respectively. These values were significant elevation compared to III and slightly greater than II. CONCLUSIONS: This study demonstrates that BS before total knee arthroplasty is associated with greater risk compared to both nonobese and obese patients. This is possibly due to a higher incidence of medical or psychiatric comorbidities determined in the Medicare BS patients, wound healing difficulties secondary to gastrointestinal malabsorption, malnourishment from prolonged catabolic state, rapid weight loss before surgery, and/or age. PMID- 27179772 TI - Response to Letter to the Editor on "No Differences Identified in Transverse Plane Biomechanics Between Medial Pivot and Rotating Platform Total Knee Implant Designs.". PMID- 27179773 TI - Survival in Patients With Primary Metastatic Renal Cell Carcinoma Treated With Sunitinib With or Without Previous Cytoreductive Nephrectomy: Results From a Population-based Registry. AB - OBJECTIVE: To evaluate the effect of cytoreductive nephrectomy (CN) on overall survival (OS) in primary metastatic renal cell carcinoma (mRCC) patients treated with first-line sunitinib. PATIENTS AND METHODS: Patients with primary mRCC treated with first-line sunitinib were selected from a Dutch population-based registry. A propensity score was calculated reflecting the probability of a patient undergoing CN prior to sunitinib using a set of known covariates, such as the Memorial Sloan Kettering Cancer Center and International mRCC Database Consortium risk factors. After propensity score matching, differences in OS were analyzed using the Kaplan-Meier method and a multivariable Cox proportional hazards model was used to evaluate the effect of CN on OS. RESULTS: A total of 227 patients met the selection criteria; 74 patients (33%) underwent CN prior to sunitinib. In the matched population, the median OS of patients who underwent CN was 17.9 months compared to 8.8 months for patients treated with sunitinib only. Multivariable analysis showed that CN was an independent predictor of OS (hazard ratio 0.61, 95% confidence interval: 0.41-0.92). A subgroup analysis of patients with a time to targeted therapy of <1 year showed a median OS of 12.7 months for patients treated with CN compared to 8.0 months for patients treated with sunitinib only. The corresponding hazard ratio was 0.67 (95% confidence interval: 0.46-0.98). CONCLUSION: This study suggests that CN may be effective. However, the benefit was modest when correcting for time from diagnosis to sunitinib. One important limitation is the use of a registry (with retrospectively collected data), which made it impossible to correct for unmeasured characteristics that could be associated with treatment choices or survival. PMID- 27179774 TI - Screening of Differently Expressed miRNA and mRNA in Prostate Cancer by Integrated Analysis of Transcription Data. AB - OBJECTIVE: The purpose of this study was to screen aberrantly expressed miRNAs and genes in prostate cancer (PCA), and further uncover the underlying mechanisms for the development of PCA. MATERIALS AND METHODS: We searched the Gene Expression Omnibus database for miRNA and gene expression datasets of PCA, and then separately integrated miRNA and gene expression datasets to identify miRNA and gene expression profiles in PCA. Target genes of differentially expressed miRNAs were predicted through miRWalk database. We matched these target genes with the list of differentially expressed genes to identify miRNA-target gene pairs whose expression was inversely correlated. The function of these target genes was annotated. RESULTS: Twenty-nine differentially expressed miRNAs and 946 differentially expressed genes were identified between PCA and normal control. Seven hundred fifty-one miRNA-target gene pairs that showed inverse expression in PCA were obtained to establish a regulatory network. In this regulatory network, 10 genes (BCL2, BNC2, CCND2, EPM2A, MRAS, NAV2, RASL12, STK33, TCEAL1, WWC2) were co-regulated by 5 miRNAs (hsa-miR-106b, hsa-miR-130b, hsa-miR-93, hsa-miR-153, hsa-miR-182). The expression of hsa-miR-182 was significantly associated with PCA survival through the online validation tool of SurvMicro, suggesting the potential use as a diagnostic or prognostic biomarker in PCA. CONCLUSION: This integrated analysis was performed to infer new miRNA regulation activities, which provides insights into the understanding of underlying molecular mechanisms of PCA, and guides for exploration of novel therapeutic targets. PMID- 27179775 TI - Variation in Testosterone Levels and Health-related Quality of Life in Men Diagnosed With Prostate Cancer on Active Surveillance. AB - OBJECTIVE: To determine the extent to which low testosterone levels impact health related quality of life in patients undergoing active surveillance (AS) for prostate cancer. MATERIALS AND METHODS: Eligible AS patients were grouped as having low, low-normal, or normal testosterone levels (<300 vs 300-400 vs >=400 ng/dL). Patients were surveyed with the Expanded Prostate Cancer Index Composite 26 (EPIC-26), Patient Reported Outcomes Measurement Information System (PROMIS), Memorial Anxiety Scale for Prostate Cancer, and treatment outlook satisfaction questions at enrollment and successively during follow-up. RESULTS: The cohort consisted of 223 patients, 74 (33%) of which had low testosterone levels. The mean age was 66.8 +/- 7.2 years, with 85% being Caucasian. Mean prostate-specific antigen did not differ between groups. Obesity was significantly higher for men with low testosterone levels (P < .01). All PROMIS-Global items were comparatively lower in men with lower testosterone. EPIC-26 scores for the sexual domain were worse in men with lower testosterone. After age and obesity adjustment, men with normal testosterone levels had significantly better PROMIS Physical, Overall, and Mental Health, EPIC-26 Hormonal, and treatment satisfaction responses when compared to those patients with low testosterone levels. Those with normal testosterone levels reported hormonal EPIC-26 domain responses 65% higher than for those with low testosterone, and 12% higher treatment satisfaction during 2-year follow-up when corrected for age and obesity (P < .05). CONCLUSION: Men with testosterone levels >=400 ng/dL reported some improved measures of health-related quality of life including greater satisfaction with treatment outcome. These findings are hypothesis generating in the controversial area of exogenous testosterone administration in men on AS. PMID- 27179776 TI - Connective tissue growth factor is activated by gastrin and involved in gastrin induced migration and invasion. AB - Connective tissue growth factor (CTGF) has been reported in gastric adenocarcinoma and in carcinoid tumors. The aim of this study was to explore a possible link between CTGF and gastrin in gastric epithelial cells and to study the role of CTGF in gastrin induced migration and invasion of AGS-GR cells. The effects of gastrin were studied using RT-qPCR, Western blot and assays for migration and invasion. We report an association between serum gastrin concentrations and CTGF abundancy in the gastric corpus mucosa of hypergastrinemic subjects and mice. We found a higher expression of CTGF in gastric mucosa tissue adjacent to tumor compared to normal control tissue. We showed that gastrin induced expression of CTGF in gastric epithelial AGS-GR cells via MEK, PKC and PKB/AKT pathways. CTGF inhibited gastrin induced migration and invasion of AGS-GR cells. We conclude that CTGF expression is stimulated by gastrin and involved in remodeling of the gastric epithelium. PMID- 27179777 TI - Methylation of miR-145a-5p promoter mediates adipocytes differentiation. AB - MicroRNAs (miRNAs, miR) play important roles in adipocyte development. Recent studies showed that the expression of several miRNAs is closely related with promoter methylation. However, it is not known whether miRNA mediates adipocytes differentiation by means of DNA methylation. Here, we showed that miR-145a-5p was poorly expressed in adipose tissue from mice fed a high fat diet (HFD). Overexpression or inhibition of miR-145a-5p was unfavorable or beneficial, respectively, for adipogenesis, and these effects were achieved by regulating adipocyte-specific genes involved in lipogenic transcription, fatty acid synthesis, and fatty acid transportation. Particularly, we first suggested that miR-145a-5p mimics or inhibitors promoted or repressed adipocytes proliferation by regulating p53 and p21, which act as cell cycle regulating factors. Surprisingly, the miR-145a-5p-repressed adipocyte differentiation was enhanced or rescued when cells treated with 5-Aza-dC were transfected with miR-145a-5p mimics or inhibitors, respectively. These data indicated that, as a new mean to positively regulate adipocyte proliferation, the process of miR-145a-5p-inhibited adipogenesis may be regulated by DNA methylation. PMID- 27179778 TI - Ultrafine particles in the airway aggravated experimental lung injury through impairment in Treg function. AB - Acute lung injury (ALI) is a life-threatening condition characterized by rapid onset alveolar-capillary damage mediated by pathogenic proinflammatory immune responses. Since exposure to airway particulate matter (PM) could significantly change the inflammatory status of the individual, we investigated whether PM instillation in the airway could alter the course of ALI, using a murine model with experimental lung injury induced by intratracheal LPS challenge. We found that PM-treated mice presented significantly aggravated lung injury, which was characterized by further reductions in body weight, increased protein concentration in the bronchoalveolar lavage (BAL), and higher mortality rate, compared to control saline-treated mice. The PM-treated mice also presented elevated lung and systemic type 1 T helper cell (Th1) frequency as well as reduced lung regulatory T cell (Treg) frequency, which was associated with severity of lung injury. Further examinations revealed that the Treg function was impaired in PM-treated mice, characterized by significantly repressed transforming growth factor beta production. Adoptive transfer of functional Tregs from control mice to PM-treated mice significantly improved their prognosis after intratracheal LPS challenge. Together, these results demonstrated that first, PM in the airway aggravated lung injury; second, severity of lung injury was associated with T cell subset imbalance in PM-treated mice; and third, PM treatment induced quantitative as well as qualitative changes in the Tregs. PMID- 27179779 TI - Restoration of the cellular secretory milieu overrides androgen dependence of in vivo generated castration resistant prostate cancer cells overexpressing the androgen receptor. AB - It is believed that growth of castration resistant prostate cancer (CRPC) cells is enabled by sensitization to minimal residual post-castrate androgen due to overexpression of the androgen receptor (AR). Evidence is derived from androgen induced colony formation in the absence of cell-secreted factors or from studies involving forced AR overexpression in hormone-dependent cells. On the other hand, standard cell line models established from CRPC patient tumors (e.g., LNCaP and VCaP) are hormone-dependent and require selection pressure in castrated mice to re-emerge as CRPC cells and the resulting tumors then tend to be insensitive to the androgen antagonist enzalutamide. Therefore, we examined established CRPC model cells produced by castration of mice bearing hormone-dependent cell line xenografts including CRPC cells overexpressing full-length AR (C4-2) or co expressing wtAR and splice-variant AR-V7 that is incapable of ligand binding (22Rv1). In standard colony formation assays, C4-2 cells were shown to be androgen-dependent and sensitive to enzalutamide whereas 22Rv1 cells were incapable of colony formation under identical conditions. However, both C4-2 and 22Rv1 cells formed colonies in conditioned media derived from the same cells or from HEK293 fibroblasts that were proven to lack androgenic activity. This effect was (i) not enhanced by androgen, (ii) insensitive to enzalutamide, (iii) dependent on AR (in C4-2) and on AR-V7 and wtAR (in 22Rv1) and (iv) sensitive to inhibitors of several signaling pathways, similar to androgen-stimulation. Therefore, during progression to CRPC in vivo, coordinate cellular changes accompanying overexpression of AR may enable cooperation between hormone independent activity of AR and actions of cellular secretory factors to completely override androgen-dependence and sensitivity to drugs targeting hormonal factors. PMID- 27179780 TI - Hypolipidemic mechanism of oryzanol components- ferulic acid and phytosterols. AB - The effect of oryzanol (well known hypolipidemic component in rice bran oil) and its chemical constituents- ferulic acid (FA) and phytosterols on hypolipidemia were investigated. METHODS AND RESULTS: Docking (in silico) studies showed that FA had a better binding ability with lipase while sterols bound well with HMG-CoA reductase. Further in vivo studies of feeding high fat (30%) to rats increased body weights, serum TC, TG, non-HDL-C and reduced HDL-C were observed, compared to normal diet fed group (ND). ORZ treated groups alleviated the lipid profile. Furthermore, increased organ weights, higher intestinal lipase activity, and liver lipid peroxidation was observed in the high-fat group (HF). These effects were ameliorated in oryzanol concentrate fed groups (ORZ). Higher fecal fat was found in ORZ groups, analysis of fecal matter by mass spectroscopy revealed the presence of FA. In vitro, a bile acid binding study supported the strong affinity of sterol towards bile acids. In conclusion, oryzanol in the intestine is cleaved into FA and sterol by intestinal lipase enzymes both lipase and HMG-CoA reductase activities were inhibited, respectively. These hydrolysates eliminated the bile acids, thus lowering lipid profiles. PMID- 27179781 TI - NS5ATP6 modulates intracellular triglyceride content through FGF21 and independently of SIRT1 and SREBP1. AB - The prevalence of nonalcoholic fatty liver disease (NAFLD) is rising strikingly in Western countries and China. The molecular biological mechanism of NAFLD remains unclear, with no effective therapies developed so far. Fibroblast growth factor 21 (FGF21) is a recently discovered hormone, with safe lipid lowering effects. FGF21 analogs are being developed for clinical application. Here we demonstrated that a novel gene, NS5ATP6, modulated intracellular triglyceride (TG) content independently of sirtuin1 (SIRT1) and sterol regulatory element binding protein 1 (SREBP1) in HepG2 cells. Interestingly, NS5ATP6 regulated FGF21 expression both at the mRNA and protein levels. The modulatory effects of NS5ATP6 on intracellular TG content depended upon FGF21. Further studies revealed that NS5ATP6 decreased the promoter activity of FGF21. In addition, NS5ATP6 regulated the expression of miR-577, which directly targeted and regulated FGF21. Therefore, miR-577 might be involved in NS5ATP6 regulation of FGF21 at the post transcriptional level. In conclusion, NS5ATP6 regulates the intracellular TG level via FGF21, and independently of SIRT1 and SREBP1. PMID- 27179782 TI - TSH increases synthesis of hepatic ATP-binding cassette subfamily A member 1 in hypercholesterolemia. AB - Epidemiological evidence suggests that thyrotropin (TSH) levels are closely correlated with the severity of hypercholesterolemia. Reverse cholesterol transfer (RCT) plays an important role in regulating bloodcholesterol. However, the molecular mechanism of hypercholesterolemia in subclinical hypothyroidism (SCH) has not been fully clarified. The SCH mouse model, which is characterized by elevated serum TSH but not thyroid hormone levels, demonstrated a significant increase in plasma cholesterol compared with controls. Interestingly, Tshr KO mice, with normal thyroid hormone levels after thyroid hormone supplementation, showed lower plasma cholesterol levels compared with their wild-type littermates. ATP binding cassette subfamily A member 1(ABCA1) is a member of the ABC superfamily, which induces transfer of intracellular cholesterol to extracellular apolipoprotein. TSH upregulated hepatic ABCA1 to promote the efflux of intercellular cumulative cholesterol, resulting in increased plasma cholesterol. These data might partially explain the pathogenesis of hypercholesterolemia in SCH. PMID- 27179783 TI - Cytosolic malate dehydrogenase regulates RANKL-mediated osteoclastogenesis via AMPK/c-Fos/NFATc1 signaling. AB - Cytosolic malate dehydrogenase (malate dehydrogenase 1, MDH1) plays pivotal roles in the malate/aspartate shuttle that might modulate metabolism between the cytosol and mitochondria. In this study, we investigated the role of MDH1 in osteoclast differentiation and formation. MDH1 expression was induced by receptor activator of nuclear factor kappa-B ligand (RANKL) treatment. Knockdown of MDH1 by infection with retrovirus containing MDH1-specific shRNA (shMDH1) reduced mature osteoclast formation and bone resorption activity. Moreover, the expression of marker genes associated with osteoclast differentiation was downregulated by shMDH1 treatment, suggesting a role of MDH1 in osteoclast differentiation. In addition, intracellular ATP production was reduced following the activation of adenosine 5' monophosphate-activated protein kinase (AMPK), a cellular energy sensor and negative regulator of RANKL-induced osteoclast differentiation, in shMDH1-infected osteoclasts compared to control cells. In addition, the expression of c-Fos and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), a critical transcription factor of osteoclastogenesis, was decreased with MDH1 knockdown during RANKL-mediated osteoclast differentiation. These findings provide strong evidence that MDH1 plays a critical role in osteoclast differentiation and function via modulation of the intracellular energy status, which might affect AMPK activity and NFATc1 expression. PMID- 27179784 TI - Serum microRNAs as diagnostic markers of endometriosis: a comprehensive array based analysis. AB - OBJECTIVE: To investigate serum microRNAs (miRNAs) in women with endometriosis. DESIGN: Case-control study. SETTING: University hospital. PATIENT(S): Women with (n = 24) and without (n = 24) endometriosis. INTERVENTION(S): Serum samples were obtained from surgically diagnosed subjects. MAIN OUTCOME MEASURE(S): miRNA from women with without endometriosis were used for microarray profiling and confirmed by means of quantitative real-time polymerase chain reaction (qRT-PCR). Receiver operating characteristic (ROC) analysis was performed on differentially expressed miRNAs. RESULT(S): miR-3613-5p, miR-6755-3p were down-regulated and miR-125b-5p, miR-150-5p, miR-342-3p, miR-143-3p, miR-145-5p, miR-500a-3p, miR-451a, miR-18a-5p were up-regulated more than 10-fold in the microarray. These results were confirmed with the use of qRT-PCR. Among the differentially expressed miRNAs, miR 125b-5p expression levels had the highest area under the ROC curve (AUC). The maximum AUC score of 1.000 was achieved when combining miR-125b-5p, miR-451a, and miR-3613-5p with the use of a logistic regression model. CONCLUSION(S): We identified several miRNAs in serum that distinguished subjects with endometriosis from those without. miR-125b-5p had the greatest potential as a single diagnostic biomarker. A combination of that miRNA with miR-451a and miR-3613-5p further improved diagnostic performance. PMID- 27179785 TI - Relationship between paternal somatic health and assisted reproductive technology outcomes. AB - OBJECTIVE: To study the association between paternal medical comorbidities and the outcomes of assisted reproductive technology (ART). DESIGN: Retrospective cohort study. SETTING: Academic reproductive medicine center. PATIENT(S): We analyzed fresh ART cycles uszing freshly ejaculated sperm from the male partner of couples undergoing ART cycles from 2004 until 2014. We recorded patient and partner demographic characteristics. The cohort was linked to hospital billing data to obtain information on selected male partners' comorbidities identified using ICD-9-CM codes. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Fertilization, clinical pregnancy, miscarriage, implantation, and live-birth rates as well as birth weights and gestational ages. RESULT(S): In all, we identified 2,690 men who underwent 5,037 fresh ART cycles. Twenty-seven percent of men had at least one medical diagnosis. Men with nervous system diseases had on average lower pregnancy rates (23% vs. 30%) and live-birth rates (15% vs. 23%) than men without nervous system diseases. Lower fertilization rates were also observed among men with respiratory diseases (61% vs. 64%) and musculoskeletal diseases (61% vs. 64%) relative to those without these diseases. In addition, men with diseases of the endocrine system had smaller children (2,970 vs. 3,210 g) than men without such diseases. Finally, men with mental disorders had children born at an earlier gestational age (36.5 vs. 38.0 weeks). CONCLUSION(S): The current report identified a possible relationship between a man's health history and IVF outcomes. As these are potentially modifiable factors, further research should determine whether treatment for men's health conditions may improve or impair IVF outcomes. PMID- 27179786 TI - Conservation of ovarian reserve across ethnicities: evidence of the evolutionary importance of maintenance of ovarian reserve. PMID- 27179787 TI - Genetic determinants of polycystic ovary syndrome: progress and future directions. AB - The field of the genetics of polycystic ovary syndrome (PCOS) has relatively recently moved into the era of genome-wide association studies. This has led to the discovery of 16 robust loci for PCOS. Some loci contain genes with clear roles in reproductive (LHCGR, FSHR, and FSHB) and metabolic (INSR and HMGA2) dysfunction in the syndrome. The next challenge facing the field is the identification of causal variants and genes and the role they play in PCOS pathophysiology. The potential for gene discovery to improve diagnosis and treatment of PCOS is promising, though there is much to be done in the field before the current findings can be translated to the clinic. PMID- 27179788 TI - Neural control of aggression in Drosophila. AB - Like most animal species, fruit flies fight to obtain and defend resources essential to survival and reproduction. Aggressive behavior in Drosophila is genetically specified and also strongly influenced by the fly's social context, past experiences and internal states, making it an excellent framework for investigating the neural mechanisms that regulate complex social behaviors. Here, I summarize our current knowledge of the neural control of aggression in Drosophila and discuss recent advances in understanding the sensory pathways that influence the decision to fight or court, the neuromodulatory control of aggression, the neural basis by which internal states can influence both fighting and courtship, and how social experience modifies aggressive behavior. PMID- 27179789 TI - Targeted inactivation of murine Ddx3x: essential roles of Ddx3x in placentation and embryogenesis. AB - The X-linked DEAD-box RNA helicase DDX3 (DDX3X) is a multifunctional protein that has been implicated in gene regulation, cell cycle control, apoptosis, and tumorigenesis. However, the precise physiological function of Ddx3x during development remains unknown. Here, we show that loss of Ddx3x results in an early post-implantation lethality in male mice. The size of the epiblast marked by Oct3/4 is dramatically reduced in embryonic day 6.5 (E6.5) Ddx3x-/Y embryos. Preferential paternal X chromosome inactivation (XCI) in extraembryonic tissues of Ddx3x heterozygous (Ddx3x-/+) female mice with a maternally inherited null allele leads to placental abnormalities and embryonic lethality during development. In the embryonic tissues, Ddx3x exhibits developmental- and tissue specific differences in escape from XCI. Targeted Ddx3x ablation in the epiblast leads to widespread apoptosis and abnormal growth, which causes embryonic lethality in the Sox2-cre/+;Ddx3xflox/Y mutant around E11.5. The observation of significant increases in gammaH2AX and p-p53Ser15 indicates DNA damage, which suggests that loss of Ddx3x leads to higher levels of genome damage. Significant upregulation of p21WAF1/Cip1 and p15Ink4b results in cell cycle arrest and apoptosis in Ddx3x-deficient cells. These results have uncovered that mouse Ddx3x is essential for both embryo and extraembryonic development. PMID- 27179790 TI - Systems-level analysis of human aging genes shed new light on mechanisms of aging. AB - Although studies over the last decades have firmly connected a number of genes and molecular pathways to aging, the aging process as a whole still remains poorly understood. To gain novel insights into the mechanisms underlying aging, instead of considering aging genes individually, we studied their characteristics at the systems level in the context of biological networks. We calculated a comprehensive set of network characteristics for human aging-related genes from the GenAge database. By comparing them with other functional groups of genes, we identified a robust group of aging-specific network characteristics. To find the structural basis and the molecular mechanisms underlying this aging-related network specificity, we also analyzed protein domain interactions and gene expression patterns across different tissues. Our study revealed that aging genes not only tend to be network hubs, playing important roles in communication among different functional modules or pathways, but also are more likely to physically interact and be co-expressed with essential genes. The high expression of aging genes across a large number of tissue types also points to a high level of connectivity among aging genes. Unexpectedly, contrary to the depletion of interactions among hub genes in biological networks, we observed close interactions among aging hubs, which renders the aging subnetworks vulnerable to random attacks and thus may contribute to the aging process. Comparison across species reveals the evolution process of the aging subnetwork. As the organisms become more complex, the complexity of its aging mechanisms increases and their aging hub genes are more functionally connected. PMID- 27179791 TI - N-acetylcysteine modulates glutamatergic dysfunction and depressive behavior in Huntington's disease. AB - Glutamatergic dysfunction has been implicated in the pathogenesis of depressive disorders and Huntington's disease (HD), in which depression is the most common psychiatric symptom. Synaptic glutamate homeostasis is regulated by cystine dependent glutamate transporters, including GLT-1 and system xc- In HD, the enzyme regulating cysteine (and subsequently cystine) production, cystathionine gamma-lygase, has recently been shown to be lowered. The aim of the present study was to establish whether cysteine supplementation, using N-acetylcysteine (NAC) could ameliorate glutamate pathology through the cystine-dependent transporters, system xc- and GLT-1. We demonstrate that the R6/1 transgenic mouse model of HD has lower basal levels of cystine, and showed depressive-like behaviors in the forced-swim test. Administration of NAC reversed these behaviors. This effect was blocked by co-administration of the system xc- and GLT-1 inhibitors CPG and DHK, showing that glutamate transporter activity was required for the antidepressant effects of NAC. NAC was also able to specifically increase glutamate in HD mice, in a glutamate transporter-dependent manner. These in vivo changes reflect changes in glutamate transporter protein in HD mice and human HD post-mortem tissue. Furthermore, NAC was able to rescue changes in key glutamate receptor proteins related to excitotoxicity in HD, including NMDAR2B. Thus, we have shown that baseline reductions in cysteine underlie glutamatergic dysfunction and depressive-like behavior in HD and these changes can be rescued by treatment with NAC. These findings have implications for the development of new therapeutic approaches for depressive disorders. PMID- 27179793 TI - G Protein-Coupled Receptors (GPCRs). PMID- 27179792 TI - BIN1 regulates BACE1 intracellular trafficking and amyloid-beta production. AB - BIN1 is a genetic risk factor of late-onset Alzheimer disease (AD), which was identified in multiple genome-wide association studies. BIN1 is a member of the amphiphysin family of proteins, and contains N-terminal Bin-Amphiphysin-Rvs and C terminal Src homology 3 domains. BIN1 is widely expressed in the mouse and human brains, and has been reported to function in the endocytosis and the endosomal sorting of membrane proteins. BACE1 is a type 1 transmembrane aspartyl protease expressed predominantly in neurons of the brain and responsible for the production of amyloid-beta peptide (Abeta). Here we report that the depletion of BIN1 increases cellular BACE1 levels through impaired endosomal trafficking and reduces BACE1 lysosomal degradation, resulting in increased Abeta production. Our findings provide a mechanistic role of BIN1 in the pathogenesis of AD as a novel genetic regulator of BACE1 levels and Abeta production. PMID- 27179794 TI - Dynamic chromatin organization: Role in development and disease. AB - The spatial organization of chromatin in the nucleus is important for proper regulation of gene expression. The cell-type specific transcription program is mainly controlled by distal regulatory elements, which can dynamically engage in long-range interactions with their target genes. These long-range interactions mostly occur within insulated genomic domains and are constrained by global organization of the chromatin, providing an extra layer of regulation. Genetic alterations can lead to disruption of spatial organization and consequently aberrant gene expression. In this review we will discuss the multiple layers of chromatin organization, how this organization changes during development and how its disruption can lead do aberrant gene expression and disease. PMID- 27179795 TI - Effect of speed endurance and strength training on performance, running economy and muscular adaptations in endurance-trained runners. AB - PURPOSE: To investigate the effects of combined strength and speed endurance (SE) training along with a reduced training volume on performance, running economy and muscular adaptations in endurance-trained runners. METHODS: Sixteen male endurance runners (VO2-max: ~60 ml kg(-1) min(-1)) were randomly assigned to either a combined strength and SE training (CSS; n = 9) or a control (CON; n = 7) group. For 8 weeks, CSS replaced their normal moderate-intensity training (~63 km week(-1)) with SE (2 * week(-1)) and strength training (2 * week(-1)) as well as aerobic high (1 * week(-1)) and moderate (1 * week(-1)) intensity training with a reduction in total volume of ~58 %, whereas CON continued their training (~45 km week(-1)). RESULTS: In CSS, 400-m and Yo-Yo intermittent recovery test performance was improved by 5 % (P < 0.01) and 19 % (P < 0.001), respectively, during the intervention period. Maximal aerobic speed was 0.6 km h(-1) higher (P < 0.05), and maximal activity of lactate dehydrogenase subunits 1 and 2 was 17 % (P < 0.05) higher after compared to before the intervention period. Time to exhaustion and peak blood lactate during an incremental treadmill test was 9 % (P < 0.05) and 32 % (P < 0.01), respectively, higher and expression of Na(+)-K(+) pump beta1 subunit was 15 % higher (P < 0.05) after compared to before the intervention period. 10-K performance, maximum oxygen uptake and running economy were unchanged. In CON, no changes were observed. CONCLUSIONS: Adding strength and speed endurance training, along with a reduced training volume, can improve short-term exercise capacity and induce muscular adaptations related to anaerobic capacity in endurance-trained runners. PMID- 27179798 TI - Regression standardization with the R package stdReg. AB - When studying the association between an exposure and an outcome, it is common to use regression models to adjust for measured confounders. The most common models in epidemiologic research are logistic regression and Cox regression, which estimate conditional (on the confounders) odds ratios and hazard ratios. When the model has been fitted, one can use regression standardization to estimate marginal measures of association. If the measured confounders are sufficient for confounding control, then the marginal association measures can be interpreted as poulation causal effects. In this paper we describe a new R package, stdReg, that carries out regression standardization with generalized linear models (e.g. logistic regression) and Cox regression models. We illustrate the package with several examples, using real data that are publicly available. PMID- 27179797 TI - Impact of aortic root size on left ventricular afterload and stroke volume. AB - PURPOSE: The left ventricle (LV) ejects blood into the proximal aorta. Age and hypertension are associated with stiffening and dilation of the aortic root, typically viewed as indicative of adverse remodeling. Based on analytical considerations, we hypothesized that a larger aortic root should be associated with lower global afterload (effective arterial elastance, EA) and larger stroke volume (SV). Moreover, as antihypertensive drugs differ in their effect on central blood pressure, we examined the role of antihypertensive drugs for the relation between aortic root size and afterload. METHODS: We studied a large group of patients (n = 1250; 61 +/- 12 years; 78 % males; 64 % hypertensives) from a single-center registry with known or suspected coronary artery disease. Aortic root size was measured by echocardiography as the diameter of the tubular portion of the ascending aorta. LV outflow tract Doppler was used to record SV. RESULTS: In the population as a whole, after adjusting for key covariates in separate regression models, aortic root size was an independent determinant of both SV and EA. This association was found to be heterogeneous and stronger in patients taking a calcium channel blocker (CCB; 10.6 % of entire population; aortic root size accounted for 8 % of the explained variance of EA). CONCLUSION: Larger aortic root size is an independent determinant of EA and SV. This association was heterogeneous and stronger in patients on CCB therapy. PMID- 27179796 TI - Analysis of cardio-pulmonary and respiratory kinetics in different body positions: impact of venous return on pulmonary measurements. AB - PURPOSE: The aim of the study was to compare the kinetics responses of heart rate (HR), pulmonary ([Formula: see text]O2pulm), and muscular ([Formula: see text]O2musc) oxygen uptake during dynamic leg exercise across different body positions (-6 degrees , 45 degrees , and 75 degrees ). METHODS: Ten healthy individuals [six men, four women; age 23.4 +/- 2.8 years; height 179.7 +/- 8.3 cm; body mass 73 +/- 12 kg (mean +/- SD)] completed pseudo-random binary sequence (PRBS) work rate (WR) changes between 30 and 80 W in each posture. HR was measured beat-to-beat by echocardiogram and [Formula: see text]O2pulm by breath by-breath gas exchange. [Formula: see text]O2musc kinetics were assessed by the procedure of Hoffmann et al. (Eur J Appl Physiol 113:1745-1754, 2013) applying a circulatory model and cross-correlation functions (CCF). RESULTS: For [Formula: see text]O2pulm kinetics significant differences between -6 degrees (CCF-values: 0.292 +/- 0.040) and 45 degrees (0.256 +/- 0.034; p < 0.01; n = 10) as well as between -6 degrees and 75 degrees (0.214 +/- 0.057; p < 0.05; n = 10) were detected at lag '40 s' of the CCF course as interaction effects (factors: Lag * Posture). HR and [Formula: see text]O2musc kinetics yield no significant differences across the postures. CONCLUSIONS: The analysis of cardio-dynamic and respiratory kinetics, especially with an emphasis on muscular and cellular level, has to consider venous return and cardiac output distortions. Simplified observations of kinetics responses resulting in time constants and time delays only should be replaced by the time-series analysis for a more sophisticated evaluation. The results illustrate that isolated [Formula: see text]O2pulm measurements without cardio-dynamic influences may not represent the kinetics responses originally revealed at muscular level. PMID- 27179799 TI - Effect of Methamphetamine Exposure on Expression of Calcium Binding Proteins in Rat Frontal Cortex and Hippocampus. AB - Methamphetamine (METH) is a psychostimulant drug with potent effects on the central nervous system that can cause psychotic symptoms similar to those of schizophrenia. Specific alterations in GABAergic neuronal markers have been reported in schizophrenia and animal models of psychotic illness. The aim of this study was to determine whether there are changes in subpopulations of GABAergic neurons, defined by the presence of calcium binding proteins (CBPs), in animal models of METH abuse. Rats received acute (Binge) doses of 4 * 6 mg/kg, a chronic escalating dose regime (0.1-4 mg/kg over 14 days) or a combination of the two and were compared with a vehicle-administered control group. Brains were taken and sections of frontal cortex (Cg1) and hippocampus (dentate gyrus and CA1-3 regions) underwent immunostaining for three CBPs [parvalbumin (PV), calbindin (CB), and calretinin (CR)]. Significant decreases in PV-immunoreactive (IR) neurons in each METH group and all regions were observed. Smaller METH-induced deficits in CB-IR cells were observed, reaching significance primarily following chronic METH regimes, while CR-IR was significantly reduced only in frontal cortex following chronic administration. These results suggest that METH regimes in rats can induce selective deficits in GABAergic neuronal subtypes similar to those seen in schizophrenia and may underlie the psychosis and/or cognitive impairment that can occur in METH abuse and dependence. PMID- 27179800 TI - Systematic review with meta-analysis: Dietary adherence influences normalization of health-related quality of life in coeliac disease. AB - BACKGROUND & AIMS: Gluten-free diet is the keystone of coeliac disease treatment. Despite adherence, some patients continue to suffer from symptoms that negatively influence health-related quality of life (HRQoL). Therefore we performed a systematic review and meta-analysis to assess the effect of gluten-free diet on HRQoL in coeliac disease. We specifically sought for determinants that negatively influenced HRQoL. METHODS: We systematically searched PubMed, EMBASE, CINAHL, PsycINFO and Cochrane Library for studies assessing HRQoL in untreated or treated adults using validated HRQoL-questionnaires from 1960 to September 2015, comparing HRQoL: (1) before and after gluten-free diet initiation or (2) in patients and non-coeliac controls. RESULTS: We included eighteen studies and sixteen were suitable for meta-analysis. Gluten-free diet significantly improves HRQoL, for psychological general well-being (PGWB)-Total (mean difference (MD) 7.34, 95% confidence interval (CI) [1.96; 12.72]; p = 0.008), SF-36 Mental Component Score (MCS) (MD 7.37, 95% CI [1.84; 12.90]; p = 0.009) and SF-36 Physical Component Score (PCS) (MD 5.72, 95% CI [1.50; 9.95]; p = 0.008). Treated patients had similar HRQoL compared with controls for PGWB-Total (MD -0.72, 95% CI [-2.71; 1.27]; p = 0.48), but significantly lower levels for SF-36 MCS (MD 4.09, 95% CI [-6.17; -2.01]; p = 0.0001) and PCS (MD -4.57, 95% CI [-6.97; 2.17]; p = 0.0002). Symptom-detected gluten-free diet adhering patients have lower HRQoL compared with screening-detected patients (MD -3.73, 95% CI [-6.77; 0.69]; p = 0.02) Strict adhering patients have better HRQoL compared with non strict adhering patients for SF-36 MCS (MD 7.70, 95% CI [4.61; 10.79]; p < 0.00001) and for SF-36 PCS (MD 3.23, 95% CI [1.33; 5.14]; p = 0.0009). CONCLUSIONS: Gluten-free diet significantly improves but does not normalize HRQoL in adults with coeliac disease. Dietary adherence improves HRQoL. Better (self reported) dietary adherence results in higher HRQoL. PMID- 27179801 TI - Factors Influencing Smallholder Farmers' Climate Change Perceptions: A Study from Farmers in Ethiopia. AB - Factors influencing climate change perceptions have vital roles in designing strategies to enrich climate change understanding. Despite this, factors that influence smallholder farmers' climate change perceptions have not yet been adequately studied. As many of the smallholder farmers live in regions where climate change is predicted to have the most negative impact, their climate change perception is of particular interest. In this study, based on data collected from Ethiopian smallholder farmers, we assessed farmers' perceptions and anticipations of past and future climate change. Furthermore, the factors influencing farmers' climate change perceptions and the relation between farmers' perceptions and available public climate information were assessed. Our findings revealed that a majority of respondents perceive warming temperatures and decreasing rainfall trends that correspond with the local meteorological record. Farmers' perceptions about the past climate did not always reflect their anticipations about the future. A substantial number of farmers' anticipations of future climate were less consistent with climate model projections. The recursive bivariate probit models employed to explore factors affecting different categories of climate change perceptions illustrate statistical significance for explanatory variables including location, gender, age, education, soil fertility status, climate change information, and access to credit services. The findings contribute to the literature by providing evidence not just on farmers' past climate perceptions but also on future climate anticipations. The identified factors help policy makers to provide targeted extension and advisory services to enrich climate change understanding and support appropriate farm-level climate change adaptations. PMID- 27179802 TI - Conservation Beyond Park Boundaries: The Impact of Buffer Zones on Deforestation and Mining Concessions in the Peruvian Amazon. AB - Many researchers have tested whether protected areas save tropical forest, but generally focus on parks and reserves, management units that have internationally recognized standing and clear objectives. Buffer zones have received considerably less attention because of their ambiguous rules and often informal status. Although buffer zones are frequently dismissed as ineffective, they warrant attention given the need for landscape-level approaches to conservation and their prevalence around the world-in Peru, buffer zones cover >10 % of the country. This study examines the effectiveness of buffer zones in the Peruvian Amazon to (a) prevent deforestation and (b) limit the extent of mining concessions. We employ covariate matching to determine the impact of 13 buffer zones on deforestation and mining concessions from 2007 to 2012. Despite variation between sites, these 13 buffer zones have prevented ~320 km(2) of forest loss within their borders during the study period and ~1739 km(2) of mining concessions, an outcome associated with the special approval process for granting formal concessions in these areas. However, a closer look at the buffer zone around the Tambopata National Reserve reveals the difficulties of controlling illegal and informal activities. According to interviews with NGO employees, government officials, and community leaders, enforcement of conservation is limited by uncertain institutional responsibilities, inadequate budgets, and corruption, although formal and community-based efforts to block illicit mining are on the rise. Landscape-level conservation not only requires clear legal protocol for addressing large-scale, formal extractive activities, but there must also be strategies and coordination to combat illegal activities. PMID- 27179803 TI - Formation of persistent organic pollutants from 2,4,5-trichlorothiophenol combustion: a density functional theory investigation. AB - Polychlorinated dibenzothiophene (PCDT) and polychlorinated thianthrene (PCTA) are sulfur analogues of dioxins, such as polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/F). In this work, we present a detailed mechanistic and kinetic analysis of PCDT and PCTA formation from the combustion of 2,4,5-trichlorothiophenol. It is shown that the formation of these persistent organic pollutants is more favourable, both kinetically and thermodynamically, than their analogous dioxin counterparts. This is rationalised in terms of the different influences of the S-H and O-H moieties in the 2,4,5-trichlorothiophenol and 2,4,5-trichlorophenol precursors. Kinetic parameters also indicate that the yield of PCDT should exceed that of PCDD. Finally, we demonstrate here that the degree and pattern of chlorination on the 2,4,5-trichlorothiophenol precursor leads to subtle thermodynamic and kinetic changes to the PCDT/PCTA formation mechanisms. Graphical abstract Formation mechanisms of persistant organic pollutants, PCDT and PCTA, from 2,4,5-trichlorothiophenol combustion, has been investigated using density functional theory. PMID- 27179804 TI - Theoretical studies on a new furazan compound bis[4-nitramino-furazanyl-3 azoxy]azofurazan (ADNAAF). AB - Bis[4-nitraminofurazanyl-3-azoxy]azofurazan (ADNAAF), synthesized in our previous work [1], contains four furazan units connected to the linkage of the azo-group and azoxy-group. For further research, some theoretical characters were studied by the density functional theoretical (DFT) method. The optimized structures and the energy gaps between the HOMO and LUMO were studied at the B3LYP/6-311++G** level. The isodesmic reaction method was used for estimating the enthalpy of formation. The detonation performances were estimated with Kamlet-Jacobs equations based on the predicted density and enthalpy of formation in the solid state. ADAAF was also calculated by the same method for comparison. It was found that the nitramino group of ADNAAF can elongate the length of adjacent C-N bonds than the amino group of ADAAF. The gas-phase and solid-phase enthalpies of formation of ADNAAF are larger than those of ADAAF. The detonation performances of ADNAAF are better than ADAAF and RDX, and similar to HMX. The trigger bond of ADNAAF is the N-N bonds in the nitramino groups, and the nitramino group is more active than the amino group (-NH2). PMID- 27179805 TI - Theoretical study on the substitution reactions of the germylenoid H2GeLiF with SiH3X (X = F, Cl, Br). AB - The substitution reactions of H2GeLiF (G) with SiH3X (X = F, Cl, Br) were investigated using calculations performed at the QCISD/6-311++G (d, p)//B3LYP/6 311+G (d, p) level of theory. The results led to the following conclusions. (i) The substitutions are nucleophilic reactions. There are two substitution paths, I and II, which both lead to the germane H2GeFSiH3. The enantiomers of this germane are obtained via these two paths if an H in SiH3X is replaced with a different group or atom. (ii) Both substitution pathways show the same order of barrier heights (SiH3F > SiH3Cl > SiH3Br). The difference between the bond energies of Li X and Si-X may explain the precedence among the substitution reactions of G with SiH3X. Path I has a lower activation barrier than path II, indicating that path I is more favorable. (iii) Comparison between the relevant insertion and substitution reactions shows that substitutions are more favorable and that the substitution product H2GeFSiH3 predominates over the insertion product. (iv) The substitution reactions of H2GeLiF with SiH3X are exothermic. PMID- 27179806 TI - pH dependence of ligand-induced human epidermal growth factor receptor activation investigated by molecular dynamics simulations. AB - The activation of human epidermal growth factor receptor (hEGFR) involves a large conformational change in its soluble extracellular domains (sECD, residues 1 620), from a tethered to an extended conformation upon binding of ligands, such as EGF. It has been reported that this dynamic process is pH-dependent, that is, hEGFR can be activated by EGF at high pH to form an extended dimer but remains as an inactive monomer at low pH. In this paper, we perform all-atom molecular dynamics (MD) simulations starting from the tethered conformation of sECD:EGF complex, at pH 5.0 and 8.5, respectively. Simulation results indicate that sECD:EGF shows different dynamic properties between the two pHs, and the complex may have a higher tendency of activation at pH 8.5. Twenty residues, including 13 histidines, in sECD:EGF have different protonation states between the two pHs (calculated by the H++ server). The charge distribution at pH 8.5 is more favorable for forming an extended conformation toward the active state of sECD than that at pH 5.0. Our study may shed light on the mechanism of pH dependence of hEGFR activation. Graphical abstract pH dependence of ligand-induced human epidermal growth factor receptor activation. PMID- 27179808 TI - Management of massive retropubic haematoma post-TVT. PMID- 27179807 TI - Impact of Heat Shock Protein A 12B Overexpression on Spinal Astrocyte Survival Against Oxygen-Glucose-Serum Deprivation/Restoration in Primary Cultured Astrocytes. AB - Heat shock protein A 12B (HSPA12B) is a newly discovered member of the heat shock protein 70 family. Preclinical evidence indicates that HSPA12B helps protect the brain from ischemic injury, although its specific function remains unclear. The aim of this study is to investigate whether HSPA12B overexpression can protect astrocytes from oxygen-glucose-serum deprivation/restoration (OGD/R) injury. We analyzed the effects of HSPA12B overexpression on spinal cord ischemia reperfusion injury and spinal astrocyte survival. After ischemia-reperfusion injury, we found that HSPA12B overexpression decreased spinal cord water content and infarct volume. MTT assay showed that HSPA12B overexpression increased astrocyte survival after OGD/R treatment. Flow cytometry results showed a marked inhibition of OGD/R-induced astrocyte apoptosis. Western blot assay showed that HSPA12B overexpression significantly increased regulatory protein B-cell lymphocyte 2 (Bcl-2) levels, whereas it decreased expression of the Bax protein, which forms a heterodimer with Bcl-2. Measurements of the level of activation of caspase-3 by Caspase-Glo(r)3/7 Assay kit showed that HSPA12B overexpression markedly inhibited caspase-3 activation. Notably, we demonstrated that the effects of HSPA12B on spinal astrocyte survival depended on activation of the PI3K/Akt signal pathway. These findings indicate that HSPA12B protects against spinal cord ischemia-reperfusion injury and may represent a potential treatment target. PMID- 27179809 TI - Total colpocleisis: technical considerations. AB - INTRODUCTION: We present a video describing the technical considerations for performing a total colpocleisis in the management of symptomatic post hysterectomy pelvic organ prolapse. METHODS: A 76-year old female presented with pelvic pressure and the presence of a palpable vaginal bulge. She had significant bother and had previously failed use of a pessary. She wasnot sexually active, with no plans for future sexual activity. Her medical history was significant for coronary artery disease with prior myocardial infarction. She had high-grade vaginal vault prolapse, without occult incontinence. After discussing observation, pessaries, restorative and obliterative procedures, she elected to undergo colpocleisis. Following hydrodissection with lidocaine with epinephrine, a quadrant-based dissection was performed to remove the vaginal epithelium circumferentially. Following this, serial purse string sutures were used to reduce the prolapse, with meticulous hemostasis. The vaginal epithelium was then closed transversely. Next, a perineorrhaphy was performed. The midline was plicated and the perineal body reconstructed. RESULTS: The patient had an uncomplicated postoperative course. At six-week follow-up she had no evidence of recurrent prolapse and was voiding without difficulty. CONCLUSIONS: Colpocleisis can provide excellent anatomic and subjective outcomes. Our goal is to highlight pertinent technical considerations in order to optimize patient outcomes. PMID- 27179810 TI - A nCounter CNV Assay to Detect HER2 Amplification: A Correlation Study with Immunohistochemistry and In Situ Hybridization in Advanced Gastric Cancer. AB - AIM: Screening amplified genes for targeted therapy with high-throughput technology is very important. The NanoString nCounter system allows multiplexed digital quantification of target molecules through the use of color-coded barcodes with the great advantage that formalin-fixed, paraffin-embedded (FFPE) tissue can be utilized. METHODS: We tested nCounter custom copy number variation (CNV) panels in 220 gastric cancer samples and evaluated the utility of this method as a screening tool for the detection of CNV using HER2. For the validation of results, we compared the nCounter results with immunohistochemistry (IHC), and we further performed in situ hybridization (ISH) in discrepant cases. RESULTS: The average HER2 gene copy numbers (CNs) by nCounter were 17.25, 2.0 and 2.61 for the HER2 IHC positive (3+), equivocal (2+), and negative cases, respectively. Out of the 16 IHC 3+ cases, 13 (81.3 %) were reported as HER2 CN gain (>=4). Gastric cancers with homogeneous HER2 overexpression or high tumor purity showed HER2 CN >=10. Among the 192 cases with HER2 IHC negative and without HER2 gene amplification, 29 showed a HER2 CN >=4 with the nCounter assay. The nCounter assay had a concordance rate of 83.4 % (kappa value, 0.35), a sensitivity of 66.7 %, a specificity of 85.2 %, a negative predictive value of 96 %, and a positive predictive value of 32.6 % compared with HER2 IHC/ISH results. Fresh frozen (FF) samples revealed a higher concordance rate (91.5 %, kappa value, 0.59) than FFPE samples (78.5 %, kappa value 0.27) and showed a high specificity (97.2 %). CONCLUSION: The nCounter CNV assay is a reliable and practical method to detect high CN variations. Given the intra-tumoral HER2 heterogeneity and normal cell contamination, additional IHC and/or FISH is necessary and needs caution in interpretation, especially in FFPE tissue samples. PMID- 27179811 TI - Reducing hazardous heavy metal ions using mangium bark waste. AB - The objective of this study was to evaluate the characteristics of mangium bark and its biosorbent ability to reduce heavy metal ions in standard solutions and wastewater and to assess changes in bark characteristics after heavy metal absorption. The experiments were conducted to determine heavy metal absorption from solutions of heavy metals alone and in mixtures as well as from wastewater. The results show that mangium bark can absorb heavy metals. Absorption percentages and capacities from single heavy metal solutions showed that Cu(2+) > Ni(2+) > Pb(2+) > Hg(2+), while those from mixture solutions showed that Hg(2+) > Cu(2+) > Pb(2+) > Ni(2+). Wastewater from gold mining only contained Cu, with an absorption percentage and capacity of 42.87 % and 0.75 mg/g, respectively. The highest absorption percentage and capacity of 92.77 % and 5.18 mg/g, respectively, were found for Hg(2+) in a mixture solution and Cu(2+) in single metal solution. The Cu(2+) absorption process in a single-metal solution changed the biosorbent characteristics of the mangium bark, yielding a decreased crystalline fraction; changed transmittance on hydroxyl, carboxyl, and carbonyl groups; and increased the presence of Cu. In conclusion, mangium bark biosorbent can reduce hazardous heavy metal ions in both standard solutions and wastewater. PMID- 27179813 TI - Co-infection with three linezolid-resistant Enterococcus faecium ST117 strain variants: what are we missing in diagnosis? PMID- 27179814 TI - Should beta-lactam antibiotics be administered by continuous infusion in critically ill patients? A survey of Australia and New Zealand intensive care unit doctors and pharmacists. AB - Although there is a biological precedent for administration of beta-lactam antibiotics by continuous or extended infusion, there is no definitive evidence of a survival benefit compared with intermittent administration. The aim of this study was to explore clinician uncertainty with regard to the administration of beta-lactam antibiotics by continuous infusion. Doctors and pharmacists in Australian and New Zealand intensive care units (ICUs) were surveyed to investigate current beta-lactam antibiotic administration practices as well as the degree of uncertainty regarding the benefit of continuous infusion of two commonly used broad-spectrum beta-lactams, namely meropenem and piperacillin/tazobactam (TZP). There were 111 respondents to the survey. Intermittent infusion was reported as standard practice for meropenem (73.9%) and TZP (82.0%). A greater proportion of pharmacists compared with doctors believed continuous infusion to be more effective than intermittent administration (85.4% vs. 34.3%, respectively; P <0.001). Both groups reported uncertainty as to whether administration by continuous infusion resulted in better patient outcomes (65.9% and 74.6%, respectively; P = 0.85). Overall, 91.0% of respondents were prepared to enrol eligible patients into a definitive randomised controlled trial on beta-lactam antibiotic administration. In conclusion, there is equipoise among clinicians working in Australian and New Zealand ICUs as to whether administration by continuous infusion offers a survival benefit in critically ill patients. PMID- 27179812 TI - Cosmet'eau-Changes in the personal care product consumption practices: from whistle-blowers to impacts on aquatic environments. AB - The Cosmet'eau project (2015-2018) investigates the "changes in the personal care product (PCP) consumption practices: from whistle-blowers to impacts on aquatic environments." In this project, the example of PCPs will be used to understand how public health concerns related to micropollutants can be addressed by public authorities-including local authorities, industries, and consumers. The project aims to characterize the possible changes in PCP consumption practices and to evaluate the impact of their implementation on aquatic contamination. Our goals are to study the whistle-blowers, the risk perception of consumers linked with their practices, and the contamination in parabens and their substitutes, triclosan, and triclocarban from wastewater to surface water. The project investigates the following potential solutions: modifications of industrial formulation or changes in consumption practices. The final purpose is to provide policy instruments for local authorities aiming at building effective strategies to fight against micropollutants in receiving waters. PMID- 27179815 TI - Impact of blaNDM-1 on fitness and pathogenicity of Escherichia coli and Klebsiella pneumoniae. AB - The objective of this study was to determine whether acquisition of New Delhi metallo-beta-lactamase-1 (NDM-1) has an impact on the fitness and virulence of Escherichia coli and Klebsiella pneumoniae. Growth kinetics and the cost of fitness of NDM-1 plasmid carriage were assessed in isogenic E. coli J53 and K. pneumoniae PRZ in vitro by pairwise competition assays. The pathogenicity of NDM 1-expressing E. coli and K. pneumoniae strains and their isogenic controls was analysed in vivo using a Galleria mellonella infection model. The cytotoxicity of NDM-1 was assessed in A549 human lung epithelial cells using the lactate dehydrogenase (LDH) assay. No differences in growth kinetics were recorded between NDM-1-expressing strains and controls (P = 0.92). A reduction in fitness of NDM-1-carrying strains was observed both for E. coli J53 and K. pneumoniae PRZ [selection rate constant (s) = -1.27 +/- 0.27 for E. coli J53 and -0.19 +/- 0.14 for K. pneumoniae PRZ; P < 0.0001]. Survival of G. mellonella larvae infected with NDM-1-expressing strains and controls was similar for E. coli J53 and K. pneumoniae PRZ. Cytotoxicity in A549 cells was not affected by NDM-1 expression (P > 0.05). The presence of blaNDM-1 did not increase the virulence or cytotoxicity of isogenic strains. However, there was a considerable cost of fitness incurred by carriage of the pNDM-1 plasmid. Interestingly, the cost of fitness was significantly higher in E. coli J53 compared with K. pneumoniae PRZ. PMID- 27179816 TI - Eradication and phenotypic tolerance of Burkholderia cenocepacia biofilms exposed to atmospheric pressure non-thermal plasma. AB - Chronic lung infection with bacteria from the Burkholderia cepacia complex (BCC), and in particular B. cenocepacia, is associated with significant morbidity and mortality in patients with cystic fibrosis (CF). B. cenocepacia can spread from person to person and exhibits intrinsic broad-spectrum antibiotic resistance. Recently, atmospheric pressure non-thermal plasmas (APNTPs) have gained increasing attention as a novel approach to the prevention and treatment of a variety of hospital-acquired infections. In this study, we evaluated an in-house designed kHz-driven plasma source for the treatment of biofilms of a number of clinical CF B. cenocepacia isolates. The results demonstrated that APNTP is an effective and efficient tool for the eradication of B. cenocepacia biofilms but that efficacy is highly variable across different isolates. Determination of phenotypic differences between isolates in an attempt to understand variability in plasma tolerance revealed that isolates which are highly tolerant to APNTP typically produce biofilms of greater biomass than their more sensitive counterparts. This indicates a potential role for biofilm matrix components in biofilm tolerance to APNTP exposure. Furthermore, significant isolate-dependent differences in catalase activity in planktonic bacteria positively correlated with phenotypic resistance to APNTP by isolates grown in biofilms. PMID- 27179817 TI - Impaired growth under iron-limiting conditions associated with the acquisition of colistin resistance in Acinetobacter baumannii. AB - Acquisition of colistin resistance in Acinetobacter baumannii has been associated with reduced bacterial fitness and virulence, although the mechanisms underlying this fitness loss have not been well characterised. In this study, the role played by environmental iron levels on the growth and survival of colistin resistant strains of A. baumannii was assessed. Growth assays with the colistin susceptible ATCC 19606 strain and its colistin-resistant derivative RC64 [colistin minimum inhibitory concentration (MIC) of 64 mg/L] demonstrated that the strains grew similarly in rich laboratory medium (Mueller-Hinton broth), whereas RC64 demonstrated impaired growth compared with ATCC 19606 in human serum (>100-fold at 24 h). Compared with RC64, ATCC 19606 grew in the presence of higher concentrations of the iron-specific chelator 2,2'-bipyridine and grew more readily under iron-limiting conditions in solid and liquid media. In addition, iron supplementation of human serum increased the growth of RC64 compared with unsupplemented human serum to a greater extent than ATCC 19606. The ability of 11 colistin-resistant clinical isolates with mutations in the pmrB gene to grow in iron-replete and iron-limiting conditions was assessed, demonstrating that eight of the strains showed reduced growth under iron limitation. Individual mutations in the pmrB gene did not directly correlate with a decreased capacity for growth under iron limitation, suggesting that mutations in pmrB may not directly produce this phenotype. Together these results indicate that acquisition of colistin resistance in A. baumannii can be associated with a decreased ability to grow in low-iron environments. PMID- 27179818 TI - Pharmacokinetic/pharmacodynamic analysis of voriconazole against Candida spp. and Aspergillus spp. in children, adolescents and adults by Monte Carlo simulation. AB - The objective of this study was to investigate the cumulative fraction of response of various voriconazole dosing regimens against six Candida and six Aspergillus spp. in immunocompromised children, immunocompromised adolescents, and adults. Using pharmacokinetic parameters and pharmacodynamic data, 5000 subject Monte Carlo simulations (MCSs) were conducted to evaluate the ability of simulated dosing strategies in terms of fAUC/MIC targets of voriconazole. According to the results of the MCSs, current voriconazole dosage regimens were all effective for children, adolescents and adults against Candida albicans, Candida parapsilosis and Candida orthopsilosis. For adults, dosing regimens of 4 mg/kg intravenous every 12 h (q12h) and 300 mg orally q12h were sufficient to treat fungal infections by six Candida spp. (C. albicans, C. parapsilosis, Candida tropicalis, Candida glabrata, Candida krusei and C. orthopsilosis) and five Aspergillus spp. (Aspergillus fumigatus, Aspergillus flavus, Aspergillus terreus, Aspergillus niger and Aspergillus nidulans). However, high doses should be recommended for children and adolescents in order to achieve better clinical efficacy against A. fumigatus and A. nidulans. The current voriconazole dosage regimens were all ineffective against A. niger for children and adolescents. All voriconazole dosage regimens were not optimal against Aspergillus versicolor. This is the first study to evaluate clinical therapy of various voriconazole dosing regimens against Candida and Aspergillus spp. infections in children, adolescents and adults using MCS. The pharmacokinetic/pharmacodynamic-based dosing strategy provided a theoretical rationale for identifying optimal voriconazole dosage regimens in children, adolescents and adults in order to maximise clinical response and minimise the probability of exposure-related toxicity. PMID- 27179819 TI - Vesicular acetylcholine transporter knock down-mice are more susceptible to inflammation, c-Fos expression and sickness behavior induced by lipopolysaccharide. AB - In addition to the well-known functions as a neurotransmitter, acetylcholine (ACh) can modulate of the immune system. Nonetheless, how endogenous ACh release inflammatory responses is still not clear. To address this question, we took advantage of an animal model with a decreased ACh release due a reduction (knockdown) in vesicular acetylcholine transporter (VAChT) expression (VAChT KD(HOM)). These animals were challenged with lipopolysaccharide (LPS). Afterwards, we evaluated sickness behavior and quantified systemic and cerebral inflammation as well as neuronal activation in the dorsal vagal complex (DVC). VAChT-KD(HOM) mice that were injected with LPS (10mg/kg) showed increased mortality rate as compared to control mice. In line with this result, a low dose of LPS (0.1mg/kg) increased the levels of pro-inflammatory (TNF-alpha, IL-1beta, and IL-6) and anti-inflammatory (IL-10) cytokines in the spleen and brain of VAChT-KD(HOM) mice in comparison with controls. Similarly, serum levels of TNF alpha and IL-6 were increased in VAChT-KD(HOM) mice. This excessive cytokine production was completely prevented by administration of a nicotinic receptor agonist (0.4mg/kg) prior to the LPS injection. Three hours after the LPS injection, c-Fos expression increased in the DVC region of VAChT-KD(HOM) mice compared to controls. In addition, VAChT-KD(HOM) mice showed behavioral changes such as lowered locomotor and exploratory activity and reduced social interaction after the LPS challenge, when compared to control mice. Taken together, our results show that the decreased ability to release ACh exacerbates systemic and cerebral inflammation and promotes neural activation and behavioral changes induced by LPS. In conclusion, our findings support the notion that activity of cholinergic pathways, which can be modulated by VAChT expression, controls inflammatory and neural responses to LPS challenge. PMID- 27179821 TI - Religious Belief and Mental Health in Lay and Consecrated Italian Teachers. AB - There is compelling evidence that teachers and clergy are stressful occupations. This study aimed to compare the rate of job strain and burnout among lay and consecrated teachers and to study the effect of religious coping on the mental health of these two groups. A cross-sectional survey study was carried out in Catholic kindergarten, preschool and primary schools of an Italian Congregation of nuns, in South Italy. The Italian versions of the Maslach Burnout Inventory Educator Survey (MBI-ES) scale, of the General Health Questionnaire (GHQ-12) and a study-specific questionnaire with sociodemographic variables and indicators of subjective (self-reported religiosity) and objective (prayer personal and church attendance) religiousness were used. Data were analyzed according to the guidelines for data processing and an analysis of the scales used. The participation rate of this study was 88 %. There was a significant difference between two groups in religiousness and job strain/burnout scores (lay teachers were the most affected group). Moreover, religiousness scores had a positive correlation with personal accomplishment, job satisfaction and perceived performance and a negative correlation with emotional exhaustion, turnover intention and morbidity psychiatric. Therefore, according to religious coping's research, prayer personal and church attendance can be recommended as two of the ways to prevent job strain and burnout in the teacher work. PMID- 27179820 TI - Free-choice high-fat diet alters circadian oscillation of energy intake in adolescent mice: role of prefrontal cortex. AB - PURPOSE: Our aim was to characterize the effect of an unfamiliar high-fat diet (HFD) on circadian feeding behaviour, plasma parameters, body weight (BW), and gene expression in the prefrontal cortex (PFC) of adolescent male mice. To this end, mice were allowed to consume a HFD during 48 h, but one group was allowed a free choice of HFD or normal chow (FC-HFD), while the other was restricted to a non-optional unfamiliar HFD feeding (NOP-HFD). METHODS: Energy intake was monitored at 6-h intervals during 48 h. Mice cohorts were killed at 6-h intervals after 48-h dietary treatment, and PFC samples dissected for RT-PCR analysis. RESULTS: Mice on the FC-HFD protocol avoided eating the standard chow, showed lower energy intake and lower BW increase than NOP-HFD mice. All animals with access to HFD exhibited nocturnal overeating, but diurnal hyperphagia was more prominent in the FC-HFD cohort. A robust increase in tyrosine hydroxylase (Th) gene expression was detected specifically during the light period of the circadian cycle in FC-HFD mice. In contrast, both protocols similarly up regulated the expression of cytosolic malic enzyme (Me1), which is very sensitive to HFD. CONCLUSION: Our data show that the PFC participates in driving motivational feeding during HFD-evoked hyperphagia and also suggest that sensory neural pathways might be relevant for the onset of eating disorders and overweight. Moreover, we have observed that animals that had the possibility of choosing between standard chow and HFD were more hyperphagic and specifically displayed an overexpression of the tyrosine hydroxylase gene. PMID- 27179822 TI - Buprenorphine and methadone treatment for opioid dependence by income, ethnicity and race of neighborhoods in New York City. AB - BACKGROUND: Geographic and demographic variation in buprenorphine and methadone treatment use in U.S. cities has not been assessed. Identifying variance in opioid maintenance is essential to improving treatment access and equity. PURPOSE: To examine the differential uptake of buprenorphine treatment in comparison to methadone treatment between 2004 and 2013 in neighborhoods in New York City characterized by income, race and ethnicity. METHODS: Social area (SA) analysis of residential zip codes of methadone and buprenorphine patients in NYC, which aggregated zip codes into five social areas with similar percentages of residents below poverty, identifying as Black non-Hispanic and as Hispanic, to examine whether treatment rates differed significantly among social areas over time. For each rate, mixed model analyses of variance were run with fixed effects for social area, year and the interaction of social area by year. RESULTS: Buprenorphine treatment increased in all social areas over time with a significantly higher rate of increase in the social area with the highest income and the lowest percentage of Black, Hispanic, and low-income residents. Methadone treatment decreased slightly in all social areas until 2011 and then increased bringing rates back to 2004 levels. Treatment patterns varied by social area. CONCLUSIONS: Buprenorphine treatment rates are increasing in all social areas, with slower uptake in moderate income mixed ethnicity areas. Methadone rates have remained stable over time. Targeted investments to promote public sector buprenorphine prescription may be necessary to reduce disparities in buprenorphine treatment and to realize its potential as a public health measure. PMID- 27179823 TI - Withdrawal exposure with withdrawal regulation training for smoking cessation: a randomized controlled pilot trial. AB - INTRODUCTION: Although withdrawal processes form a key motivational basis for cigarette use, smoking cessation treatments appear to exert only modest effects on withdrawal. One treatment option for further reducing withdrawal severity would be to provide smokers with withdrawal regulation training. The objective of this study was to pilot a smoking cessation intervention comprising withdrawal exposure with withdrawal regulation training. METHODS: Adult smokers (N=80) were randomized to one of two conditions: 1) Withdrawal Exposure with Withdrawal Regulation Training (WT), which included the development and application of individualized withdrawal regulation strategies over four separate sessions that spanned the first four hours of abstinence; 2) or Relaxation Control (RC) training, which controlled for the therapeutic contact of WT. All sessions occurred before the quit date, after which differential treatment was discontinued and all participants received brief counseling, nicotine replacement therapy, and self-help literature. Biochemically-confirmed (CO<=3) seven-day point-prevalence abstinence was assessed at Months 2 and 3 after end-of treatment. RESULTS: Treatment completion and ratings of credibility and efficacy were high and equivalent across conditions. 22.2% of participants in the WT condition were abstinent at both time points, whereas 0% and 4.2% of participants in the RC condition were abstinent at Months 2 and 3 (Month 3 OR=6.5 [0.73, 59.19]). In-session withdrawal ratings suggested WT improved regulation of withdrawal symptoms, which were in turn associated with abstinence. CONCLUSIONS: This small pilot study suggests that WT promotes abstinence by enhancing withdrawal regulation. Results warrant further investigation of this innovative treatment approach. PMID- 27179824 TI - Identifying mortality risks in patients with opioid use disorder using brief screening assessment: Secondary mental health clinical records analysis. AB - BACKGROUND: Risk assessments are widely used, but their ability to predict outcomes in opioid use disorder (OUD) treatment remains unclear. Therefore, the aim was to investigate if addiction-specific brief risk screening is effective in identifying high mortality risk groups and if subsequent clinical actions following risk assessment impacts on mortality levels. METHODS: Opioid use disorder (OUD) patients were identified in the South London and Maudsley Case Register. Deaths were identified through database linkage to the national mortality dataset. Cox and competing-risk regression were used to model associations between brief risk assessment domains and all-cause and overdose mortality in 4488 OUD patients, with up-to 6-year follow-up time where 227 deaths were registered. Data were stratified by admission to general mental health services. RESULTS: All-cause mortality was significantly associated with unsafe injecting (HR 1.53, 95% CI 1.10-2.11) and clinically appraised likelihood of accidental overdose (HR 1.48, 95% CI 1.00-2.19). Overdose-mortality was significantly associated with unsafe injecting (SHR 2.52, 95% CI 1.11-5.70) and clinically appraised suicidality (SHR 2.89, 95% CI 1.38-6.03). Suicidality was associated with a twofold increase in mortality risk among OUD patients who were not admitted to mental health services within 2 months of their risk assessment (HR 2.03, 95% CI 1.67-3.24). CONCLUSIONS: Diagnosis-specific brief risk screening can identify OUD patient subgroups at increased risk of all-cause and overdose mortality. OUD patients, where suicidality is evident, who are not admitted into services are particularly vulnerable. PMID- 27179825 TI - Enhanced external counterpulsation (EECP) improves biomarkers of glycemic control in patients with non-insulin-dependent type II diabetes mellitus for up to 3 months following treatment. AB - AIMS: The purpose of the present study was to evaluate the potential clinical benefits of EECP on glycemic parameters [fasting plasma glucose (FPG), postprandial glucose (PPG120), glycosylated hemoglobin (HbA1c)] in patients with a clinical diagnosis of type II diabetes mellitus (T2DM). METHODS: Thirty subjects (60.7 +/- 1.9 years) with T2DM were randomly assigned (2:1 ratio) to receive either 35 1-h sessions of EECP (n = 20) or time-matched control of standard care (n = 10). FPG, PPG120, and HbA1c were evaluated before and at 48 h, 2 weeks, 3 and 6 months following EECP treatment or time-matched control. RESULTS: EECP significantly decreased FPG (-14.6 and -12.0 %), PPG120 (-14.6 and 13.5 %), and HbA1c (-11.5 and -19.6 %) 48 h following EECP and 2 weeks following EECP, respectively. HbA1c remained significantly reduced at 3 months following EECP (-14.3 %). The homeostasis model assessment of insulin resistance (-31.1 %) and whole-body composite insulin sensitivity index (+54.2 %) were significantly improved 48 h following EECP. Nitrite/nitrate (NO x ) was significantly increased 48 h following EECP (+48.4 %) and 2 weeks (+51.9 %) following EECP treatment. CONCLUSIONS: Our findings provide novel evidence that EECP improves glycemic control in patients with T2DM that persist for up to 3 months following treatment. PMID- 27179826 TI - Evolving Challenges for Targeting Metabolic Abnormalities in Heart Failure. PMID- 27179827 TI - Trends in the Use of Guideline-Directed Therapies Among Dialysis Patients Hospitalized With Systolic Heart Failure: Findings From the American Heart Association Get With The Guidelines-Heart Failure Program. AB - OBJECTIVES: The purpose of this study was to determine the temporal trends in the adherence to heart failure (HF)-related process of care measures and clinical outcomes among patients with acute decompensated HF with reduced ejection fraction (HFrEF) and end-stage renal disease (ESRD). BACKGROUND: Previous studies have demonstrated significant underuse of evidence-based HF therapies among patients with coexisting ESRD and HFrEF. However, it is unclear if the proportional use of evidence-based medical therapies and associated clinical outcomes among these patients has changed over time. METHODS: Get With The Guidelines-HF study participants who were admitted for acute HFrEF between January 2005 and June 2014 were stratified into 3 groups on the basis of their admission renal function: normal renal function, renal insufficiency without dialysis, and dialysis. Temporal change in proportional adherence to the HF related process of care measures and incidence of clinical outcomes (1-year mortality, HF hospitalization, and all-cause hospitalization) during the study period was evaluated across the 3 renal function groups. RESULTS: The study included 111,846 patients with HFrEF from 390 participating centers, of whom 19% had renal insufficiency but who did not require dialysis, and 3% were on dialysis. There was a significant temporal increase in adherence to evidence based medical therapies (angiotensin-converting enzyme inhibitor/angiotensin receptor blocker: p trend <0.0001, beta-blockers: p trend = 0.0089; post discharge follow-up referral: p trend <0.0001) and defect-free composite care (p trend <0.0001) among dialysis patients. An improvement in adherence to these measures was also observed among patients with normal renal function and patients with renal insufficiency without a need for dialysis. There was no significant change in cumulative incidence of clinical outcomes over time among the HF patients on dialysis. CONCLUSIONS: In a large contemporary cohort of HFrEF patients with ESRD, adherence to the HF process of care measures has improved significantly over the past 10 years. Unlike patients with normal renal function, there was no significant change in 1-year clinical outcomes over time among HF patients on dialysis. PMID- 27179828 TI - Right Ventricular Contractile Reserve and Pulmonary Circulation Uncoupling During Exercise Challenge in Heart Failure: Pathophysiology and Clinical Phenotypes. AB - OBJECTIVES: Right ventricular (RV) exercise contractile reserve (RVECR), its phenotypes, and its functional correlates are among the unresolved issues with regard to the role of the right ventricle in heart failure (HF) syndrome, and understanding these issues constitutes the objective of this study. BACKGROUND: Although the role of the right ventricle in HF syndrome might be fundamental, the pathophysiology of the failing right ventricle has not been extensively investigated. METHODS: Ninety-seven patients with HF (mean age 64 years, 70% men, mean left ventricular ejection fraction 33 +/- 10%) underwent maximal exercise stress echocardiographic and cardiopulmonary exercise testing. RVECR and RV-to pulmonary circulation (PC) coupling were assessed using the length-force relationship (tricuspid annular plane systolic excursion [TAPSE] vs. pulmonary artery systolic pressure) and the slope of mean pulmonary artery pressure versus cardiac output. On the basis of TAPSE, patients were categorized into 3 groups: those with TAPSE at rest >=16 mm (group A, n = 60) and those with TAPSE at rest <16 mm, who were divided according to median TAPSE at peak exercise (15.5 mm) into 2 subgroups (group B, >=15.5 mm, n = 19; group C, <15.5 mm, n = 18). RESULTS: Although they had similar left ventricular ejection fractions and rest RV impairment, compared with patients in group C, those in group B showed some degree of RVECR (upward shift of the length-force relationship), better RV-to-PC coupling (lower mean pulmonary artery pressure vs. cardiac output slope), and greater ventilatory efficiency (lower slope of minute ventilation to carbon dioxide output). Rest mitral regurgitation and net changes in pulmonary artery systolic pressure were the variables retained in the best regression model as correlates of RVECR. CONCLUSIONS: In patients with HF, RVECR unmasks different phenotypes. Impaired RV function at rest might not invariably lead to unfavorable RVECR and exercise RV-to-PC coupling. Testing these variables appears useful even in more advanced stages of HF to define various clinical conditions and, most likely, to define different levels of risk. PMID- 27179829 TI - Skeletal Muscle Mitochondrial Content, Oxidative Capacity, and Mfn2 Expression Are Reduced in Older Patients With Heart Failure and Preserved Ejection Fraction and Are Related to Exercise Intolerance. AB - OBJECTIVES: The aim of this study was to examine skeletal muscle mitochondria content, oxidative capacity, and the expression of key mitochondrial dynamics proteins in patients with heart failure with preserved ejection fraction (HFpEF), as well as to determine potential relationships with measures of exercise performance. BACKGROUND: Multiple lines of evidence indicate that severely reduced peak exercise oxygen uptake (peak VO2) in older patients with HFpEF is related to abnormal skeletal muscle oxygen utilization. Mitochondria are key regulators of skeletal muscle metabolism; however, little is known about how these organelles are affected in HFpEF. METHODS: Both vastus lateralis skeletal muscle citrate synthase activity and the expression of porin and regulators of mitochondrial fusion were examined in older patients with HFpEF (n = 20) and healthy, age-matched control subjects (n = 17). RESULTS: Compared with age matched healthy control subjects, mitochondrial content assessed by porin expression was 46% lower (p = 0.01), citrate synthase activity was 29% lower (p = 0.01), and Mfn2 (mitofusin 2) expression was 54% lower (p <0.001) in patients with HFpEF. Expression of porin was significantly positively correlated with both peak VO2 and 6-min walk distance (r = 0.48, p = 0.003 and r = 0.33, p = 0.05, respectively). Expression of Mfn2 was also significantly positively correlated with both peak VO2 and 6-min walk distance (r = 0.40, p = 0.02 and r = 0.37, p = 0.03 respectively). CONCLUSIONS: These findings suggest that skeletal muscle oxidative capacity, mitochondrial content, and mitochondrial fusion are abnormal in older patients with HFpEF and might contribute to their severe exercise intolerance. PMID- 27179831 TI - Myocardial Structural and Functional Response After Long-Term Mechanical Unloading With Continuous Flow Left Ventricular Assist Device: Axial Versus Centrifugal Flow. AB - OBJECTIVES: The aim of this study was to assess the impact of continuous-flow left ventricular assist device (LVAD) type-axial flow (AX) versus centrifugal flow (CR)-on myocardial structural and functional response following mechanical unloading. BACKGROUND: The use of continuous-flow LVADs is increasing steadily as a therapeutic option for patients with end-stage heart failure who are not responsive to medical therapy. Whether the type of mechanical unloading influences the myocardial response is yet to be determined. METHODS: A total of 133 consecutive patients with end-stage heart failure implanted with continuous flow LVADs (AX, n = 107 [HeartMate II Thoratec Corporation, Pleasanton, California]; CR, n = 26 [HeartWare, HeartWare International, Framingham, Massachusetts]) were prospectively studied. Echocardiograms were obtained pre LVAD implantation and then serially at 1, 2, 3, 4, 6, 9, and 12 months post implantation. RESULTS: The 2 pump types led to similar degrees of mechanical unloading as assessed by invasive hemodynamic status and frequency of aortic valve opening. Myocardial structural and functional parameters showed significant improvement post-LVAD in both AX and CR groups. Left ventricular ejection fraction increased significantly from a mean of 18% to 28% and 26% post-LVAD in the AX and CR groups, respectively. Left ventricular end-systolic volume index and left ventricular end-diastolic volume index decreased significantly as early as 30 days post-implantation in the 2 groups. The degree of myocardial structural or functional response between patients in the AX or CR groups appeared to be comparable. CONCLUSIONS: Long-term mechanical unloading induced by AX and CR LVADs, while operating within their routine clinical range, seems to exert comparable effects on myocardial structural and functional parameters. PMID- 27179830 TI - The Importance of Worsening Heart Failure in Ambulatory Patients: Definition, Characteristics, and Effects of Amino-Terminal Pro-B-Type Natriuretic Peptide Guided Therapy. AB - OBJECTIVES: The goal of this study was to define and assess the significance of worsening heart failure (WHF) in patients with chronic ambulatory heart failure with reduced ejection fraction (HFrEF). BACKGROUND: WHF has been identified as a potentially relevant clinical event in patients with acute heart failure (HF) and is increasingly used as an endpoint in clinical trials. No standardized definition of WHF exists. It remains uncertain how WHF relates to risk for other HF events or how treatment may affect WHF. METHODS: A total of 151 symptomatic patients with chronic HFrEF were randomized to standard of care HF management or a goal to lower N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations <=1,000 pg/ml in addition to standard of care. WHF was prospectively defined as: 1) new or progressive symptoms and/or signs of decompensated HF; and 2) unplanned intensification of diuretic therapy. RESULTS: Over a mean follow-up of 10 months, 45 subjects developed WHF. At baseline, patients developing incident WHF had higher ejection fraction (31% vs. 25%; p = 0.03), were more likely to have jugular venous distension and edema (p < 0.02), were less likely to receive angiotensin-converting enzyme inhibitors or received these agents at lower doses (p < 0.04), and also received higher loop diuretic doses (p < 0.001). Occurrence of WHF was strongly associated with subsequent HF hospitalization/cardiovascular death (hazard ratio, landmark analysis: 18.8; 95% confidence interval: 5.7 to 62.5; p < 0.001). NT-proBNP-guided care reduced the incidence of WHF in adjusted analyses (hazard ratio: 0.52; p = 0.06) and improved event-free survival (log-rank test p = 0.04). CONCLUSIONS: In chronic HFrEF, WHF was associated with substantial risk for morbidity and mortality. NT-proBNP guided care reduced risk for WHF. PMID- 27179832 TI - Brain Natriuretic Peptide Treatment and Heart Failure Prevention: Reliving the Mistakes of the Past or Charting a New Course for the Future? PMID- 27179833 TI - A Suprainstitutional Network for Remote Extracorporeal Life Support: A Retrospective Cohort Study. AB - OBJECTIVES: This study sought to evaluate patient outcome within the Dusseldorf Extracorporeal Life Support (ECLS) Network, a suprainstitutional network for rapid-response remote ECLS and to define survival-based predictors. BACKGROUND: Mobile venoarterial extracorporeal membrane oxygenation (vaECMO) used for ECLS has become a treatment option for a patient population with an otherwise fatal prognosis. However, outcome data remain scarce and institutional standards required to manage these patients are still poorly defined. METHODS: This retrospective cohort study analyzes the outcome of 115 patients consecutively treated between July 2011 and October 2014 within the Dusseldorf ECLS Network due to refractory circulatory failure. RESULTS: Of the 115 patients (56 +/- 15 years of age, vaECMO initiation under cardiopulmonary resuscitation [CPR] 77%, CPR duration 45 [range 5 to 90] min), 50 patients (44%) survived to primary discharge and 38 patients (33%) were alive after a median follow-up of 1.5 years (95% confidence interval [CI]: 1.2 to 1.7). Thirty-seven (97%) of the long-term survivors showed a favorable neurological outcome. Risk factors associated with mortality during vaECMO were CPR duration (hazard ratio [HR]: 1.006; 95% CI: 1.00 to 1.01) and ischemic stroke (HR: 2.63; 95% CI: 1.52 to 4.56). Risk factors associated with mortality after vaECMO weaning were renal failure (HR: 6.60; 95% CI: 2.72 to 16.01) and sepsis (HR: 3.6; 95% CI: 1.50 to 8.69). Visceral ischemia had a negative impact (HR: 0.30; 95% CI: 0.11 to 0.84) whereas assist device implantation promoted successful vaECMO weaning (HR: 2.95; 95% CI: 1.65 to 5.25). Further, 3 distinct risk groups with significant differences in survival could be identified, demonstrating that in patients with no or short CPR mortality was not conditioned by age, whereas in patients with prolonged CPR young age was associated with increased survival. CONCLUSIONS: This study illustrates the implementation of a suprainstitutional ECLS Network. Further, our data suggest that mobile vaECMO is beneficial for a larger patient population than actually expected, especially regarding young patients presenting with prolonged CPR or patients regardless of age with no or short CPR. PMID- 27179834 TI - Plasma Corin as a Predictor of Cardiovascular Events in Patients With Chronic Heart Failure. AB - OBJECTIVES: The aim of this study was to determine the prognostic value of plasma corin in patients with chronic heart failure (CHF). BACKGROUND: In recent years, accumulating evidence has indicated that corin plays a critical role in regulating blood pressure and cardiac function. METHODS: We enrolled 1,148 consecutive CHF patients in a prospective cohort study and explored the association between plasma corin levels and clinical prognosis using multivariate Cox regression analysis. RESULTS: Patients with low corin levels (<458 pg/ml) were more likely to be women and to be hypertensive. Low corin was found to be associated with an increase in New York Heart Association (NYHA) functional class and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, and a decrease in left ventricular ejection fraction (LVEF) and the estimated glomerular filtration rate (eGFR). Multivariate Cox regression analysis suggested that log corin was an independent predictor of major adverse cardiac event(s) (MACE) (hazard ratio: 0.62; 95% confidence interval: 0.39 to 0.95), together with age, diabetes, NYHA functional class, LVEF, eGFR, and log NT-proBNP. In addition, log corin was also a significant predictor for cardiovascular death (p = 0.041) and heart failure rehospitalization (p = 0.015) after adjustment for clinical variables and established biomarkers of adverse prognosis. The Kaplan-Meier survival curves showed that low corin was a significant predictor of MACE in patients with NT-proBNP levels above and below the median. CONCLUSIONS: Our study demonstrates that plasma corin is a valuable prognostic marker of MACE in patients with CHF, independent of established conventional risk factors. PMID- 27179835 TI - Clinical Implications of Intrarenal Hemodynamic Evaluation by Doppler Ultrasonography in Heart Failure. AB - OBJECTIVES: This study clarified the characteristics of intrarenal Doppler ultrasonography (IRD) profiles and their prognostic implications in heart failure (HF). BACKGROUND: IRD can assess intrarenal hemodynamics. METHODS: Initially, 224 patients with HF were prospectively enrolled; 151 inpatients were enrolled during hospitalization for HF, and 73 were outpatients in our institution. In IRD profiles of interlobar vessels, the arterial resistance index (RI), venous impedance index (VII), and intrarenal venous flow (IRVF) pattern were assessed. Patients were followed to evaluate the associations with 1-year prognosis. Primary endpoints included death from cardiovascular disease and unplanned hospitalization for HF. RESULTS: Finally, 217 patients with adequate IRD images were enrolled. IRD profiles were associated with conventional risk factors for HF. In particular, IRVF was associated with mean right atrial pressure (RAP); 3 IRVF patterns were stratified by RAP (in a continuous pattern: 5.4 +/- 2.5; in a biphasic pattern: 9.5 +/- 3.5; and in a monophasic pattern: 14.9 +/- 4.3 mm Hg; p < 0.001). In addition, the monophasic IRVF pattern had a poorer prognosis than the other patterns (log rank p < 0.001), and prognosis was poorer for the biphasic pattern than for the continuous flow pattern (log rank p = 0.01). Multivariate Cox proportional hazard model analysis revealed that IRVF patterns were associated with the endpoints, independent of other HF risk factors. CONCLUSIONS: IRVF patterns, rather than RI, depended on RAP, suggesting a correlation with renal congestion. In addition, IRVF patterns strongly correlated with clinical outcomes independent of RAP and other risk factors and might provide additional information to stratify vulnerable HF patients. PMID- 27179836 TI - Does Survival on the Heart Transplant Waiting List Depend on the Underlying Heart Disease? AB - OBJECTIVES: The aim of this study was to identify differences in survival on the basis of type of heart disease while awaiting orthotopic heart transplantation (OHT). BACKGROUND: Patients with restrictive cardiomyopathy (RCM), congenital heart disease (CHD), or hypertrophic cardiomyopathy (HCM) may be at a disadvantage while awaiting OHT because they often are poor candidates for mechanical circulatory support and/or inotropes. METHODS: The study included all adults in the Scientific Registry of Transplant Recipients database awaiting OHT from 2004 to 2014, and outcomes were evaluated on the basis of type of heart disease. The primary endpoint was time to all-cause mortality, censored at last patient follow-up and time of transplantation. Multivariate Cox proportional hazards modeling was performed to evaluate survival by type of cardiomyopathy. RESULTS: There were 14,447 patients with DCM, 823 with RCM, 11,799 with ischemic cardiomyopathy (ICM), 602 with HCM, 964 with CHD, 584 with valvular disease, and 1,528 in the "other" category (including 1,216 for retransplantation). During median follow-up of 3.7 months, 4,943 patients died (1,253 women, 3,690 men). After adjusting for possible confounding variables including age, renal function, inotropes, mechanical ventilation, and mechanical circulatory support, the adjusted hazard ratios by diagnoses relative to DCM were 1.70 for RCM (95% confidence interval [CI]: 1.43 to 2.02), 1.10 for ICM (95% CI: 1.03 to 1.18), 1.23 for HCM (95% CI: 0.98 to 1.54), 1.30 for valvular disease (95% CI: 1.07 to 1.57), 1.37 for CHD (95% CI: 1.17 to 1.61), and 1.51 for "other" diagnoses (95% CI: 1.34 to 1.69). Sex was a significant modifier of mortality for ICM, RCM, and "other" diagnoses (p < 0.05 for interaction). CONCLUSIONS: In the United States, patients with RCM, CHD, or prior heart transplantation had a higher risk for death while awaiting OHT than patients with DCM, ICM, HCM, or valvular heart disease. PMID- 27179837 TI - Lymphangiography is a diagnostic and therapeutic intervention for patients with plastic bronchitis after the Fontan operation. PMID- 27179839 TI - "Some people see innovation as change, but we have never really seen it like that. It's understanding things and making them better." Adapted from Tim Cook, Chief Executive Officer of Apple. PMID- 27179838 TI - Safety and feasibility of near-infrared image-guided lymphatic mapping of regional lymph nodes in esophageal cancer. AB - OBJECTIVE: To assess safety and feasibility of an intraoperative, minimally invasive near-infrared (NIR) image-guided approach to lymphatic mapping in patients with esophageal cancer. METHODS: Although local lymph nodes (LNs) are removed with the esophageal specimen, no techniques are available to identify the regional LNs (separate from the esophagus) during esophagectomy. We hypothesize that NIR imaging can identify regional LNs with the potential to improve staging and guide the extent of lymphadenectomy. Nine of the 10 patients enrolled had resectable esophageal adenocarcinoma and underwent NIR mapping following peritumoral submucosal injection of indocyanine green (ICG) alone or premixed in human serum albumin (ICG:HSA) before resection. NIR imaging was performed in situ and ex vivo. RESULTS: In 6 of the 10 patients, intraoperative NIR imaging demonstrated an NIR signal at all tumors and in 2 to 6 NIR(+) regional LNs. NIR(+) LNs were not identified in 4 patients: 1 patient with occult stage IV disease, for whom further imaging was not performed and thus was excluded from analysis, and 3 patients in whom ICG was used without HSA. Identification of local LNs on the esophagus was obscured by a peritumoral background. Importantly, the pathological status of NIR(+) regional LNs reflected overall regional nodal status. CONCLUSIONS: NIR lymphatic mapping is safe and feasible in patients with esophageal cancer and can identify regional LNs when ICG:HSA is used. Although more work is needed to improve background signals and local LN identification, intraoperative detection of regional NIR(+) LNs allows an in-depth histological analysis of LN basins not commonly scrutinized as part of the specimen and may improve the detection of occult nodal disease. PMID- 27179840 TI - Constriction, effusion, or both: Radical pericardiectomy with improved outcomes. PMID- 27179841 TI - More or less: Sometimes more is more if it's the lesser of evils. PMID- 27179842 TI - The lung torsion dilemma: Detorsion without resection or resection without detorsion? PMID- 27179843 TI - How many leaflets in the mitral valve? PMID- 27179844 TI - Transfemoral transcatheter valve-in-valve-in-valve replacement. PMID- 27179845 TI - Don't sweat it: Medical management of hyperhidrosis. PMID- 27179846 TI - Multiple arterial grafting: Please don't confuse me with the facts. PMID- 27179847 TI - Effect of Noninvasive Ventilation Delivered by Helmet vs Face Mask on the Rate of Endotracheal Intubation in Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial. AB - IMPORTANCE: Noninvasive ventilation (NIV) with a face mask is relatively ineffective at preventing endotracheal intubation in patients with acute respiratory distress syndrome (ARDS). Delivery of NIV with a helmet may be a superior strategy for these patients. OBJECTIVE: To determine whether NIV delivered by helmet improves intubation rate among patients with ARDS. DESIGN, SETTING, AND PARTICIPANTS: Single-center randomized clinical trial of 83 patients with ARDS requiring NIV delivered by face mask for at least 8 hours while in the medical intensive care unit at the University of Chicago between October 3, 2012, through September 21, 2015. INTERVENTIONS: Patients were randomly assigned to continue face mask NIV or switch to a helmet for NIV support for a planned enrollment of 206 patients (103 patients per group). The helmet is a transparent hood that covers the entire head of the patient and has a rubber collar neck seal. Early trial termination resulted in 44 patients randomized to the helmet group and 39 to the face mask group. MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of patients who required endotracheal intubation. Secondary outcomes included 28-day invasive ventilator-free days (ie, days alive without mechanical ventilation), duration of ICU and hospital length of stay, and hospital and 90-day mortality. RESULTS: Eighty-three patients (45% women; median age, 59 years; median Acute Physiology and Chronic Health Evaluation [APACHE] II score, 26) were included in the analysis after the trial was stopped early based on predefined criteria for efficacy. The intubation rate was 61.5% (n = 24) for the face mask group and 18.2% (n = 8) for the helmet group (absolute difference, 43.3%; 95% CI, -62.4% to -24.3%; P < .001). The number of ventilator-free days was significantly higher in the helmet group (28 vs 12.5, P < .001). At 90 days, 15 patients (34.1%) in the helmet group died compared with 22 patients (56.4%) in the face mask group (absolute difference, -22.3%; 95% CI, -43.3 to -1.4; P = .02). Adverse events included 3 interface-related skin ulcers for each group (ie, 7.6% in the face mask group had nose ulcers and 6.8% in the helmet group had neck ulcers). CONCLUSIONS AND RELEVANCE: Among patients with ARDS, treatment with helmet NIV resulted in a significant reduction of intubation rates. There was also a statistically significant reduction in 90-day mortality with helmet NIV. Multicenter studies are needed to replicate these findings. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01680783. PMID- 27179848 TI - A Validation Study for the Use of ROS1 Immunohistochemical Staining in Screening for ROS1 Translocations in Lung Cancer. AB - INTRODUCTION: The presence of ROS proto-oncogene 1, receptor tyrosine kinase gene (ROS1) rearrangements in lung cancers confers sensitivity to ROS kinase inhibitors, including crizotinib. However, they are rare abnormalities (in ~1% of non-small cell lung carcinomas) that are typically identified by fluorescence in situ hybridization (FISH), and so screening using immunohistochemical (IHC) staining would be both cost- and time-efficient. METHODS: A cohort of lung tumors negative for other common mutations related to targeted therapies were screened to assess the sensitivity and specificity of IHC staining in detecting ROS1 gene rearrangements, enriched by four other cases first identified by FISH. A review of published data was also undertaken. RESULTS: IHC staining was 100% sensitive (95% confidence interval: 48-100) and 83% specific (95% confidence interval: 86 100) overall when an h-score higher than 100 was used. Patients with ROS1 gene rearrangements were younger and typically never-smokers, with the tumors all being adenocarcinomas with higher-grade architectural features and focal signet ring morphologic features (two of five). Four patients treated with crizotinib showed a partial response, with three also showing a partial response to pemetrexed. Three of four patients remain alive at 13, 27, and 31 months, respectively. CONCLUSION: IHC staining can be used to screen for ROS1 gene rearrangements, with patients herein showing a response to crizotinib. Patients with tumors that test positive according to IHC staining but negative according to FISH were also identified, which may have implications for treatment selection. PMID- 27179850 TI - Effects of partial replacement of corn and alfalfa silage with tall fescue hay on total-tract digestibility and lactation performance in dairy cows. AB - Our objective was to evaluate the effects of replacing either corn or alfalfa silage with tall fescue hay on total-tract neutral detergent fiber (NDF) digestibility and lactation performance in dairy cows. Twenty-four primiparous (75+/-35 d in milk) and 40 multiparous (68+/-19 d in milk) Holstein cows were blocked by parity and randomly assigned to 1 of 4 treatment groups in a pen equipped with 32 feeding gates to record intake by cow. Each gate was randomly assigned to 1 treatment group; thus, each cow had access to all 8 gates within the respective treatment and cow was the experimental unit. Treatments were formulated to replace either corn silage (CS) or alfalfa silage (AS) with tall fescue hay (TF) as follows (DM basis): 33% AS and 67% CS (control; 33AS67CS), 60% TF and 40% AS (60TF40AS), 60% TF and 40% CS (60TF40CS), and 33% TF and 67% CS (33TF67CS). The experiment was a 7-wk continuous lactation trial with a 2-wk covariate period. Milk production did not differ among treatments and averaged 40.4 kg/d. Fat yield and concentration and protein yield and concentration did not differ among treatments and averaged 1.58 kg/d, 3.94%, 1.28 kg/d, and 3.15%, respectively. Dry matter intake was greater for 33AS67CS (24.5 kg/d) compared with 60TF40CS (22.1 kg/d) and 33TF67CS (22.7 kg/d), and tended to be greater than 60TF40AS (23.2 kg/d). In vivo total-tract dry matter digestibility did not differ among treatments and averaged 66.2%. In vivo total-tract NDF digestibility was lower for 33AS67CS (37.8%) compared with 60TF40AS (44.4%) and 33TF67CS (45.3%), and similar to 60TF40CS (42.4%). In vivo total-tract NDF digestibility and an estimate of in situ total-tract NDF digestibility were similar between techniques across all treatment diets (42.3 vs. 42.6%, respectively). Inclusion of tall fescue grass hay increased the total-tract NDF digestibility of the diet and has the potential to replace corn silage and alfalfa silage and maintain milk production if economically feasible based on current market prices. PMID- 27179851 TI - Effectiveness of rubber seed oil and flaxseed oil to enhance the alpha-linolenic acid content in milk from dairy cows. AB - This experiment was conducted to investigate effect of rubber seed oil compared with flaxseed oil when fed alone or in combination on milk yield, milk composition, and alpha-linolenic acid (ALA) concentration in milk of dairy cows. Forty-eight mid-lactation Holstein dairy cows were randomly assigned to 1 of 4 treatments according to a completely randomized design. Cows were fed a basal diet (control; CON) or a basal diet supplemented with 4% rubber seed oil (RO), 4% flaxseed oil (FO), or 2% rubber seed oil plus 2% flaxseed oil (RFO) on a dry matter basis for 9 wk. Feed intake, milk protein percentage, and milk fat levels did not differ between the treatments. Cows fed the RO, FO, or RFO treatments had a higher milk yield than the CON group (up to 10.5% more), whereas milk fat percentages decreased. Compared with the CON, milk concentration of ALA was substantially higher in cows receiving RO or RFO, and was doubled in cows receiving FO. The ALA yield (g/d) increased by 31.0, 70.3, and 33.4% in milk from cows fed RO, FO, or RFO, respectively, compared with the CON. Both C18:1 trans-11 (vaccenic acid) and C18:2 cis-9,trans-11 (conjugated linoleic acid; CLA) levels were higher in cows fed added flaxseed or rubber seed oil. The CLA yield (g/d) increased by 336, 492, and 484% in cows fed RO, FO, or RFO, respectively, compared with the CON. The increase in vaccenic acid, ALA, and CLA was greater in cows fed RFO than in cows fed RO alone. Compared with the CON, the milk fat from cows fed any of the dietary supplements had a higher concentration of unsaturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids; conversely, the saturated fatty acids levels in milk fat were 30.5% lower. Insulin and growth hormones were not affected by dietary treatments; however, we noted an increase in both cholesterol and nonesterified fatty acids levels in the RO, FO, or RFO treatments. These results indicate that rubber seed oil and flaxseed oil will increase milk production and the concentration of functional fatty acids (ALA, vaccenic acid, and CLA) in milk fat while decreasing the content of saturated fatty acids. PMID- 27179852 TI - Effects of milk somatic cell counts on some physicochemical and functional characteristics of skim and whole milk powders. AB - The aim of this work was to study the influence of milk somatic cell count (SCC) levels on spray-dried milk powders. For this reason, 3 cow milks with different SCC (<300,000, 300,000-700,000, >700,000 SCC/mL) were processed into skim (SMP) and whole milk powder (WMP). The effect of SCC on the physicochemical and functional characteristics of the milk powders and textural properties of set type yogurts produced from reconstituted milk powders with different SCC was evaluated. A crucial difference was noted between milk powders depending on different SCC. Protein values and ash content of powder samples decreased correlatively with increasing SCC. The hydroxymethylfurfural content of SMP was higher than WMP. We noted an increase in hydroxymethylfurfural content of both SMP and WMP depending on elevated SCC. Solubility index of SMP and WMP was 1.280 to 1.632 and 0.940 to 1.208mL, respectively; with increasing SCC, solubility index was affected adversely. The highest foam stability was determined in SMP containing >700,000 SCC. Bulk density of SMP and WMP was between 0.682 and 0.708 and 0.660 to 0.685g/cm(3), respectively. An increase was observed in scorched particle of both SMP and WMP depending on increasing SCC. We found significant differences in particle size distribution of milk powders produced from milk with SCC at different levels. Although WMP had more uniform and big particle structure, SMP had more specific area. A negative correlation was noted between yogurt texture and SCC. Results indicate that milk SCC has negative influences on milk powder quality. PMID- 27179853 TI - Transcriptome expression analysis of candidate milk genes affecting cheese related traits in 2 sheep breeds. AB - Because ewe milk is principally used for cheese making, its quality is related to its content of total solids and the way in which milk constituents influence cheese yield and determine the technological and organoleptic characteristics of dairy products. Therefore, an in-depth knowledge of the expression levels of milk genes influencing cheese-related traits is essential. In the present study, the milk transcriptome data set of 2 dairy sheep breeds, Assaf and Spanish Churra, was used to evaluate the expression levels of 77 transcripts related to cheese yield and quality traits. For the comparison between both breeds, we selected the RNA sequencing (RNA-Seq) data at d 10 of lactation because this is the time point at which within and between breed differences due to lactation length are minimal. The evaluated genes encode major milk proteins (caseins and whey proteins), endogenous proteases, and enzymes related to fatty acid metabolism and citrate content. Through this analysis, we identified the genes predominantly expressed in each of the analyzed pathways that appear to be key genes for traits related to sheep milk cheese. Among the highly expressed genes in both breeds were the genes encoding caseins and whey proteins (CSN2, CSN3, CSN1S1, ENSOARG00000005099/PAEP, CSN1S2, LALBA), genes related to lipid metabolism (BTN1A1, XDH, FASN, ADFP, SCD, H-FABP, ACSS2), and one endogenous protease (CTSB). Moreover, a differential expression analysis between Churra and Assaf sheep allowed us to identify 7 genes that are significantly differentially expressed between the 2 breeds. These genes were mainly linked to endogenous protease activity (CTSL, CTSK, KLK10, KLK6, SERPINE2). Additionally, there were 2 differentially expressed genes coding for an intracellular fatty acid transporter (FABP4), an intermediate molecule of the citric acid cycle (SUCNR1), and 2 heat shock proteins (HSP70, HSPB8) that could be related to high protein production. The differential expression of these genes could have a direct influence on the different phenotypes observed between the 2 analyzed breeds. PMID- 27179854 TI - Structural markers of the evolution of whey protein isolate powder during aging and effects on foaming properties. AB - The market for dairy powders, including high added-value products (e.g., infant formulas, protein isolates) has increased continuously over the past decade. However, the processing and storage of whey protein isolate (WPI) powders can result in changes in their structural and functional properties. It is therefore of great importance to understand the mechanisms and to identify the structural markers involved in the aging of WPI powders to control their end use properties. This study was performed to determine the effects of different storage conditions on protein lactosylations, protein denaturation in WPI, and in parallel on their foaming and interfacial properties. Six storage conditions involving different temperatures (theta) and water activities (aw) were studied for periods of up to 12mo. The results showed that for theta<=20 degrees C, foaming properties of powders did not significantly differ from nonaged whey protein isolates (reference), regardless of the aw. On the other hand, powders presented significant levels of denaturation/aggregation and protein modification involving first protein lactosylation and then degradation of Maillard reaction products, resulting in a higher browning index compared with the reference, starting from the early stage of storage at 60 degrees C. These changes resulted in a higher foam density and a slightly better foam stability (whisking) at 6mo. At 40 degrees C, powders showed transitional evolution. The findings of this study will make it possible to define maximum storage durations and to recommend optimal storage conditions in accordance with WPI powder end-use properties. PMID- 27179855 TI - Short communication: Chemical and sensory characteristics of Canestrato di Moliterno cheese manufactured in spring. AB - Canestrato di Moliterno is an Italian Protected Geographical Indication hard cheese, made in winter and spring from a mixture of ewe and goat milks, that has been poorly investigated. The present study was aimed at characterizing the cheese made in the warm season. Two series of samples, ripened in traditional rooms called fondaco as indicated in the official protocol of production, were taken from the main certified producers. The cheeses were analyzed for gross composition; proteolysis and lipolysis; volatile fraction; and organoleptic features. Gross composition was not completely homogeneous among the samples, but primary proteolysis and lipolysis were quite uniform. We observed variations in secondary proteolysis, likely caused by fluctuations in environmental conditions in the fondaco. The sensory profiles of the samples were homogeneous: the cheese was soluble, greasy, and adhesive, with a sheepfold and buttery odor. The main taste attributes were fermented, pungent, and bitter. Overall, the results of this study provide an initial contribution to the characterization of Canestrato di Moliterno, and could be used to improve marketing strategies. PMID- 27179849 TI - Effect of Endobronchial Coils vs Usual Care on Exercise Tolerance in Patients With Severe Emphysema: The RENEW Randomized Clinical Trial. AB - IMPORTANCE: Preliminary clinical trials have demonstrated that endobronchial coils compress emphysematous lung tissue and may improve lung function, exercise tolerance, and symptoms in patients with emphysema and severe lung hyperinflation. OBJECTIVE: To determine the effectiveness and safety of endobronchial coil treatment. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial conducted among 315 patients with emphysema and severe air trapping recruited from 21 North American and 5 European sites from December 2012 through November 2015. INTERVENTIONS: Participants were randomly assigned to continue usual care alone (guideline based, including pulmonary rehabilitation and bronchodilators; n = 157) vs usual care plus bilateral coil treatment (n = 158) involving 2 sequential procedures 4 months apart in which 10 to 14 coils were bronchoscopically placed in a single lobe of each lung. MAIN OUTCOMES AND MEASURES: The primary effectiveness outcome was difference in absolute change in 6-minute-walk distance between baseline and 12 months (minimal clinically important difference [MCID], 25 m). Secondary end points included the difference between groups in 6-minute walk distance responder rate, absolute change in quality of life using the St George's Respiratory Questionnaire (MCID, 4) and change in forced expiratory volume in the first second (FEV1; MCID, 10%). The primary safety analysis compared the proportion of participants experiencing at least 1 of 7 prespecified major complications. RESULTS: Among 315 participants (mean age, 64 years; 52% women), 90% completed the 12-month follow-up. Median change in 6-minute walk distance at 12 months was 10.3 m with coil treatment vs 7.6 m with usual care, with a between-group difference of 14.6 m (Hodges-Lehmann 97.5% CI, 0.4 m to infinity; 1-sided P = .02). Improvement of at least 25 m occurred in 40.0% of patients in the coil group vs 26.9% with usual care (odds ratio, 1.8 [97.5% CI, 1.1 to infinity]; unadjusted between-group difference, 11.8% [97.5% CI, 1.0% to infinity]; 1-sided P = .01). The between-group difference in median change in FEV1 was 7.0% (97.5% CI, 3.4% to infinity; 1-sided P < .001), and the between-group St George's Respiratory Questionnaire score improved -8.9 points (97.5% CI, -infinity to -6.3 points; 1-sided P < .001), each favoring the coil group. Major complications (including pneumonia requiring hospitalization and other potentially life-threatening or fatal events) occurred in 34.8% of coil participants vs 19.1% of usual care (P = .002). Other serious adverse events including pneumonia (20% coil vs 4.5% usual care) and pneumothorax (9.7% vs 0.6%, respectively) occurred more frequently in the coil group. CONCLUSIONS AND RELEVANCE: Among patients with emphysema and severe hyperinflation treated for 12 months, the use of endobronchial coils compared with usual care resulted in an improvement in median exercise tolerance that was modest and of uncertain clinical importance, with a higher likelihood of major complications. Further follow-up is needed to assess long-term effects on health outcomes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01608490. PMID- 27179856 TI - Genetic and environmental variation in bovine milk infrared spectra. AB - Fourier transform infrared (FTIR) spectroscopy is widely used to determine milk composition. In this study, 1,060 milk infrared wavenumbers ranging from 925 to 5,008cm(-1) of 1,748 Holstein Friesian cows on 371 herds in the Netherlands were available. The extent to which infrared wavenumbers are affected by genetic and environmental factors was investigated. Inter-herd heritabilities of 1,060 infrared wavenumbers ranged from 0 to 0.63, indicating that the genetic background of infrared wavenumbers differs considerably. The majority of the wavenumbers have moderate to high inter-herd heritabilities ranging from 0.20 to 0.60. The diacylglycerol O-acyltransferase 1 (DGAT1), stearoyl-CoA desaturase (SCD1), kappa-casein (CSN3), and beta-lactoglobulin (LGB) polymorphisms are known to have a large effect on milk composition, and therefore we studied the effects of these polymorphisms on infrared wavenumbers. The DGAT1 polymorphism had highly significant effects on many wavenumbers. In contrast, the SCD1 polymorphism did not significantly affect any of the wavenumbers. The SCD1 is known to have a strong effect on the content of C10:1, C12:1, C14:1, and C16:1 fatty acids. Therefore, these results suggest that FTIR spectra contain little direct information on these monounsaturated fatty acids. The CSN3 and LGB polymorphisms had significant effects on a few wavenumbers. Differences between herds explained 10 to 25% of the total variance for most wavenumbers. This suggests that the wavenumbers of milk FTIR spectra are indicative for differences in feeding and management between herds. The wavenumbers between 1,619 and 1,674cm(-1) and between 3,073 and 3,667cm(-1) are strongly influenced by water absorption and usually excluded when setting up prediction equations. However, we found that some of the wavenumbers in the water absorption region are affected by the DGAT1 polymorphism and lactation stage. This suggests that these wavenumbers contain useful information regarding milk composition. PMID- 27179857 TI - Genomic evaluation, breed identification, and population structure of Guernsey cattle in North America, Great Britain, and the Isle of Guernsey. AB - As of December 2015, 2,376 Guernsey bulls and cows had genotypes from collaboration between the United States, Canada, the United Kingdom, and the Isle of Guernsey. Of those, 439 bulls and 504 cows had traditional US evaluations, which provided sufficient data to justify investigation of the possible benefits of genomic evaluation for the Guernsey breed. Evaluation accuracy was assessed using a traditional 4-yr cutoff study. Twenty-two traits were analyzed (5 yield traits, 3 functional traits, and 14 conformation traits). Mean reliability gain over that for parent average was 16.8 percentage points across traits, which compares with 8.2, 18.5, 20.0, and 32.6 percentage points reported for Ayrshires, Brown Swiss, Jerseys, and Holsteins, respectively. Highest Guernsey reliability gains were for rump width (44.5 percentage points) and dairy form (40.5 percentage points); lowest gains were for teat length (1.9 percentage points) and rear legs (side view) (2.3 percentage points). Slight reliability losses (1.5 to 4.5 percentage points) were found for udder cleft, final score, and udder depth as well as a larger loss (13.6 percentage points) for fore udder attachment. Twenty-one single nucleotide polymorphisms were identified for Guernsey breed determination and can be used in routine genotype quality control to confirm breed and identify crossbreds. No haplotypes that affect fertility were identified from the current data set. Principal component analysis showed some divergence of US and Isle of Guernsey subpopulations. However, the overlap of US, Canadian, UK, and Isle of Guernsey subpopulations indicated the presence of gene flow, and the similarities in the subpopulations supports a common genomic evaluation system across the regions. PMID- 27179858 TI - Genetic parameters of calcium, phosphorus, magnesium, and potassium serum concentrations during the first 8 days after calving in Holstein cows. AB - Calcium, Mg, P, and K are of great importance for the health and productivity of dairy cows after calving. So far genetic studies have focused on clinical hypocalcemia, leaving the genetic parameters of these macroelements unstudied. Our objective was to estimate the genetic parameters of Ca, Mg, P, and K serum concentrations and their changes during the first 8d after calving. The study was conducted in 9 herds located in northern Greece, with 1,021 Holstein cows enrolled from November 2010 until November 2012. No herd used any kind of preventive measures for hypocalcemia. Pedigree information for all cows was available. A total of 35 cows were diagnosed and treated for periparturient paresis and, therefore, excluded from the study. The remaining 986 cows were included in genetic analysis. The distribution of cows across parities was 459 (parity 1), 234 (parity 2), 158 (parity 3), and 135 (parity >=4). A sample of blood was taken from each cow on d1, 2, 4, and 8 after calving and serum concentrations of Ca, P, Mg, and K were measured in each sample. A final data set of 15,390 biochemical records was created consisting of 3,903 Ca, 3,902 P, 3,903Mg, and 3,682K measurements. Moreover, changes of these concentrations between d1 and 4 as well as 1 and 8 after calving were calculated and treated as different traits. Random regression models were used to analyze the data. Results showed that daily heritabilities of Ca, P, and Mg concentrations traits were moderate to high (0.20-0.43), whereas those of K were low to moderate (0.12 0.23). Regarding concentration changes, only Mg change between d1 and 8 after calving had a significant heritability of 0.18. Genetic correlations between Ca, P, Mg, and K concentrations and their concentration changes from d1 to 4 and 1 to 8 after calving were not significantly different from zero. Most phenotypic correlations among Ca, P, Mg, and K concentrations were positive and low (0.09 0.16), whereas the correlation between P and Mg was negative and low (-0.16). Phenotypic correlations among macromineral concentrations on d1 and their changes from d1 to 4 and 1 to 8 after calving varied for each macromineral. This study revealed that genetic selection for normal Ca, P, Mg, and K concentrations in the first week of lactation is possible and could facilitate the management of their deficiencies during the early stages of lactation. PMID- 27179859 TI - Effects of slow-release urea and rumen-protected methionine and histidine on mammalian target of rapamycin (mTOR) signaling and ubiquitin proteasome-related gene expression in skeletal muscle of dairy cows. AB - The mammalian target of rapamycin (mTOR) is a major regulator of protein synthesis, whereas the ubiquitin-proteasome system (UPS) is regarded as the main proteolytic pathway in skeletal muscle. The objective of the current study was to investigate the effects of slow-release urea and rumen-protected (RP) Met and His supplementation of a metabolizable protein (MP)-deficient diet on the abundance of key components of the mTOR pathway and of the UPS in skeletal muscle of dairy cows. Sixty Holstein cows were blocked based on days in milk and milk yield and were randomly assigned within block to 1 of 5 diets in a 10-wk experiment (including the first 2 wk as covariate period) as follows: (1) MP-adequate diet (AMP; 107% of MP requirements, based on the National Research Council requirements); (2) MP-deficient diet (DMP; 95% of MP requirements); (3) DMP supplemented with slow-release urea (DMPU); (4) DMPU supplemented with RPMet (DMPUM); and (5) DMPUM supplemented with RPHis (DMPUMH). Muscle biopsies were collected from longissimus dorsi during the last week of the experiment. The mRNA abundance of key mTOR signaling genes was not affected by the treatments. The phosphorylated (P)-mTOR protein was or tended to be greater for DMP compared with DMPU and AMP, respectively. The P-mTOR protein in DMPUMH was decreased when compared against DMPUM. The P-ribosomal protein S6 tended to be increased by DMPUM compared with DMPU. The abundance of total-S6 was or tended to be greater for DMP compared with AMP and DMPU, respectively. The mRNA abundance of ubiquitin activating and conjugating enzymes was not affected by the treatments, whereas that of muscle ring-finger protein 1 (MuRF-1) was greater in DMP than DMPU. The increased abundance of mTOR-associated signaling proteins and MuRF-1 mRNA abundance indicates a higher rate of protein turnover in muscle of DMP-fed cows. The reduced abundance of P-mTOR by supplementation of RPHis may suggest that His is likely partitioned to the mammary gland in favor of milk protein synthesis rather than to the skeletal muscle in dairy cows fed MP-deficient diets. PMID- 27179860 TI - The nonlinear effect of somatic cell count on milk composition, coagulation properties, curd firmness modeling, cheese yield, and curd nutrient recovery. AB - The aim of this study was to investigate the relationships between somatic cell count (SCC) in milk and several milk technological traits at the individual cow level. In particular, we determined the effects of very low to very high SCC on traits related to (1) milk yield and composition; (2) coagulation properties, including the traditional milk coagulation properties (MCP) and the new curd firming model parameters; and (3) cheese yield and recovery of milk nutrients in the curd (or loss in the whey). Milk samples from 1,271 Brown Swiss cows from 85 herds were used. Nine coagulation traits were measured: 3 traditional MCP [rennet coagulation time (RCT, min), curd firming rate (k20, min), and curd firmness after 30 min (a30, mm)] and 6 new curd firming and syneresis traits [potential asymptotic curd firmness at infinite time (CFP, mm), curd firming instant rate constant (kCF, % * min(-1)), syneresis instant rate constant (kSR, % * min(-1)), rennet coagulation time estimated using the equation (RCTeq, min), maximum curd firmness achieved within 45 min (CFmax, mm), and time at achievement of CFmax (tmax, min)]. The observed cheese-making traits included 3 cheese yield traits (%CYCURD, %CYSOLIDS, and %CYWATER, which represented the weights of curd, total solids, and water, respectively, as a percentage of the weight of the processed milk) and 4 nutrient recoveries in the curd (RECFAT, RECPROTEIN, RECSOLIDS, and RECENERGY, which each represented the percentage ratio between the nutrient in the curd and milk). Data were analyzed using a linear mixed model with the fixed effects of days in milk, parity, and somatic cell score (SCS), and the random effect of herd-date. Somatic cell score had strong influences on casein number and lactose, and also affected pH; these were traits characterized by a quadratic pattern of the data. The results also showed a negative linear relationship between SCS and milk yield. Somatic cell score influenced almost all of the tested coagulation traits (both traditional and modeled), with the exceptions of k20, CFP, and kSR. Gelation was delayed when the SCS decreased (slightly) and when it increased (strongly) with respect to a value of 2, as confirmed by the quadratic patterns observed for both RCT and RCTeq. The SCS effect on a30 showed a quadratic pattern almost opposite to that observed for RCT. With respect to the CFt parameters, kCF decreased linearly as SCS increased, resulting in a linear decrease of CFmax and a quadratic pattern for tmax. Milk SCS attained significance for %CYCURD, %CYWATER, and RECPROTEIN. As the SCS increased beyond 3, we observed a progressive quadratic decrease of the water retained in the curd (%CYWATER), which caused a parallel decrease in %CYCURD. With respect to RECPROTEIN, the negative effect of SCS was almost linear. Recovery of fat and (consequently) RECENERGY was characterized by a more evident quadratic trend, with the most favorable values associated with an intermediate SCS. Together, our results confirmed that high SCS has a negative effect on milk composition and technological traits, highlighting the nonlinear trends of some traits across the different classes of SCS. Moreover, we report that a very low SCS has a negative effect on some technological traits of milk. PMID- 27179861 TI - Novel concepts on the role of prostaglandins on luteal maintenance and maternal recognition and establishment of pregnancy in ruminants. AB - In ruminants, the corpus luteum (CL) of early pregnancy is resistant to luteolysis. Prostaglandin (PG)E2 is considered a luteoprotective mediator. Early studies indicate that during maternal recognition of pregnancy (MRP) in ruminants, a factor(s) from the conceptus or gravid uterus reaches the ovary locally through the utero-ovarian plexus (UOP) and protects the CL from luteolysis. The local nature of the embryonic antiluteolytic or luteoprotective effect precludes any direct effect of a protein transported or acting between the gravid uterus and CL in ruminants. During MRP, interferon tau (IFNT) secreted by the trophoblast of the conceptus inhibits endometrial pulsatile release of PGF2alpha and increases endometrial PGE2. Our recent studies indicate that (1) luteal PG biosynthesis is selectively directed toward PGF2alpha at the time of luteolysis and toward PGE2 at the time of establishment of pregnancy (ESP); (2) the ability of the CL of early pregnancy to resist luteolysis is likely due to increased intraluteal biosynthesis and signaling of PGE2; and (3) endometrial PGE2 is transported from the uterus to the CL through the UOP vascular route during ESP in sheep. Intrauterine co-administration of IFNT and prostaglandin E2 synthase 1 (PGES-1) inhibitor reestablishes endometrial PGF2alpha pulses and regresses the CL. In contrast, intrauterine co-administration of IFNT and PGES-1 inhibitor along with intraovarian administration of PGE2 rescues the CL. Together, the accumulating information provides compelling evidence that PGE2 produced by the CL in response to endometrial PGE2 induced by pregnancy may counteract the luteolytic effect of PGF2alpha as an additional luteoprotective mechanism during MRP or ESP in ruminants. Targeting PGE2 biosynthesis and signaling selectively in the endometrium or CL may provide luteoprotective therapy to improve reproductive efficiency in ruminants. PMID- 27179862 TI - Short communication: The effects of dry matter and length of storage on the composition and nutritive value of alfalfa silage. AB - During the ensiling of feeds, various processes result in chemical changes that can affect their ultimate nutritive value at feed out. The primary objective of this study was to evaluate the effect of prolonged ensiling times on potential changes in in vitro digestibility of neutral detergent fiber (NDF-D) of alfalfa ensiled at about 33% [low dry matter (DM), LDM] or 45% (high DM, HDM) whole-plant DM. Alfalfa from the same field (direct chopped or wilted) was chopped with a conventional forage harvester set for a theoretical length of cut of 0.95 cm and ensiled in mini silos for 45, 180, 270, and 360 d. Fresh forages and silages were analyzed for nutrient content, fermentation end-products, and 30-h NDF-D. The pH of the fresh forages ranged from 6.1 to 6.2 and decreased to approximately 4.7 and 4.3 in HDM and LDM silages, respectively. Production of acids and alcohols were less in HDM compared with LDM as expected. Concentrations of soluble protein and NH3-N also increased with time of storage as expected but soluble protein was greater, whereas NH3-N was lower in HDM compared with LDM silage. The effect of length of storage and DM on hemicellulose and NDF concentrations were very small, whereas DM content at harvest tended to slightly increase the concentration of acid detergent fiber in HDM compared with LDM up to 270 d of storage. The NDF-D was greater in fresh forage compared with corresponding silages. However, time of storage between 45 and 360 d had no effect on the NDF-D of alfalfa silage, regardless of DM concentration at ensiling. PMID- 27179863 TI - Assessment of the effect of methionine supplementation and inclusion of hydrolyzed wheat protein in milk protein-based milk replacers on the performance of intensively fed Holstein calves. AB - The objectives of this study were to compare 2 milk replacers containing only milk proteins with or without supplemental Met, and to compare a milk replacer containing hydrolyzed wheat protein at 4.5% of dry matter (DM) and supplemental Lys and Met against the 2 all-milk-protein formulas, by assessing their effect on the growth performance, efficiency, and plasma urea nitrogen of pre-weaning Holstein calves. Thus, 57 Holstein calves were allotted to the following 3 treatments: (1) a skim milk plus whey protein concentrate-based milk replacer (SMWP) containing about 2.6% Lys and 0.6% Met on a DM basis; (2) SMWP + M based on skim milk and whey proteins, containing about 2.6% Lys, and supplemental Met to reach 0.9% on a DM basis; and (3) a skim milk plus whey protein concentrate plus 4.5% of the DM as hydrolyzed wheat protein based milk replacer (HWP + LM) where the wheat protein replaced 50% of the whey protein concentrate, and also contained supplemental Lys and Met to match the profile of SMWP + M (i.e., Lys 2.6 and Met 0.9% on DM basis). No difference in any of the responses was observed by supplementing the milk protein based formula with Met or when hydrolyzed wheat protein was added to the formula. Results indicate that (1) a milk replacer based on skim milk protein and whey protein with a Lys concentration of ~2.6% does not benefit from Met supplementation, and (2) milk replacer containing 4.5% of the DM as hydrolyzed wheat protein and supplemented with Lys and Met can support the same growth performance as milk protein-based formulas. PMID- 27179864 TI - A dynamic, mechanistic model of metabolism in adipose tissue of lactating dairy cattle. AB - Research in dairy cattle biology has resulted in a large body of knowledge on nutrition and metabolism in support of milk production and efficiency. This quantitative knowledge has been compiled in several model systems to balance and evaluate rations and predict requirements. There are also systems models for metabolism and reproduction in the cow that can be used to support research programs. Adipose tissue plays a significant role in the success and efficiency of lactation, and recent research has resulted in several data sets on genomic differences and changes in gene transcription of adipose tissue in dairy cattle. To fully use this knowledge, we need to build and expand mechanistic, dynamic models that integrate control of metabolism and production. Therefore, we constructed a second-generation dynamic, mechanistic model of adipose tissue metabolism of dairy cattle. The model describes the biochemical interconversions of glucose, acetate, beta-hydroxybutyrate (BHB), glycerol, C16 fatty acids, and triacylglycerols. Data gathered from our own research and published references were used to set equation forms and parameter values. Acetate, glucose, BHB, and fatty acids are taken up from blood. The fatty acids are activated to the acyl coenzyme A moieties. Enzymatically catalyzed reactions are explicitly described with parameters including maximal velocity and substrate sensitivity. The control of enzyme activity is partially carried out by insulin and norepinephrine, portraying control in the cow. Model behavior was adequate, with sensitive responses to changing substrates and hormones. Increased nutrient uptake and increased insulin stimulate triacylglycerol synthesis, whereas a reduction in nutrient availability or increase in norepinephrine increases triacylglycerol hydrolysis and free fatty acid release to blood. This model can form a basis for more sophisticated integration of existing knowledge and future studies on metabolic efficiency of dairy cattle. PMID- 27179865 TI - Proteolytic activity of Enterococcus faecalis VB63F for reduction of allergenicity of bovine milk proteins. AB - With the aim of screening proteolytic strains of lactic acid bacteria to evaluate their potential for the reduction of allergenicity of the major bovine milk proteins, we isolated a new proteolytic strain of Enterococcus faecalis (Ent. faecalis VB63F) from raw bovine milk. The proteases produced by this strain had strong activity against caseins (alphaS1-, alphaS2-, and beta-casein), in both skim milk and sodium caseinate. However, only partial hydrolysis of whey proteins was observed. Proteolysis of Na-caseinate and whey proteins, observed after sodium dodecyl sulfate-PAGE, was confirmed by analysis of peptide profiles by reversed-phase HPLC. Inhibition of proteolysis with EDTA indicated that the proteases produced by Ent. faecalis VB63F belonged to the group of metalloproteases. The optimal conditions for their activity were 42 degrees C and pH 6.5. The majority of assessed virulence genes were absent in Ent. faecalis VB63F. The obtained results suggest that Ent. faecalis VB63F could be efficient in reducing the immunoreactivity of bovine milk proteins. PMID- 27179866 TI - Insulin-dependent glucose metabolism in dairy cows with variable fat mobilization around calving. AB - Dairy cows undergo significant metabolic and endocrine changes during the transition from pregnancy to lactation, and impaired insulin action influences nutrient partitioning toward the fetus and the mammary gland. Because impaired insulin action during transition is thought to be related to elevated body condition and body fat mobilization, we hypothesized that over-conditioned cows with excessive body fat mobilization around calving may have impaired insulin metabolism compared with cows with low fat mobilization. Nineteen dairy cows were grouped according to their average concentration of total liver fat (LFC) after calving in low [LLFC; LFC <24% total fat/dry matter (DM); n=9] and high (HLFC; LFC >24.4% total fat/DM; n=10) fat-mobilizing cows. Blood samples were taken from wk 7 antepartum (ap) to wk 5 postpartum (pp) to determine plasma concentrations of glucose, insulin, glucagon, and adiponectin. We applied euglycemic hyperinsulinemic (EGHIC) and hyperglycemic clamps (HGC) in wk 5 ap and wk 3 pp to measure insulin responsiveness in peripheral tissue and pancreatic insulin secretion during the transition period. Before and during the pp EGHIC, [(13)C6] glucose was infused to determine the rate of glucose appearance (GlucRa) and glucose oxidation (GOx). Body condition, back fat thickness, and energy-corrected milk were greater, but energy balance was lower in HLFC than in LLFC. Plasma concentrations of glucose, insulin, glucagon, and adiponectin decreased at calving, and this was followed by an immediate increase of glucagon and adiponectin after calving. Insulin concentrations ap were higher in HLFC than in LLFC cows, but the EGHIC indicated no differences in peripheral insulin responsiveness among cows ap and pp. However, GlucRa and GOx:GlucRa during the pp EGHIC were greater in HLFC than in LLFC cows. During HGC, pancreatic insulin secretion was lower, but the glucose infusion rate was higher pp than ap in both groups. Plasma concentrations of nonesterified fatty acids decreased during HGC and EGHIC, but in both clamps, pp nonesterified fatty acid concentrations did not reach the ap levels. The study demonstrated a minor influence of different degrees of body fat mobilization on insulin metabolism in cows during the transition period. The distinct decrease in the glucose-dependent release of insulin pp is the most striking finding that explains the impaired insulin action after calving, but does not explain differences in body fat mobilization between HLFC and LLFC cows. PMID- 27179867 TI - Multilocus sequence typing of Lactobacillus casei isolates from naturally fermented foods in China and Mongolia. AB - Lactobacillus casei is a lactic acid bacterium used in manufacturing of many fermented food products. To investigate the genetic diversity and population biology of this food-related bacterium, 224 Lb. casei isolates and 5 reference isolates were examined by multilocus sequence typing (MLST). Among them, 224 Lb. casei isolates were isolated from homemade fermented foods, including naturally fermented dairy products, acidic gruel, and Sichuan pickles from 38 different regions in China and Mongolia. The MLST scheme was developed based on the analysis of 10 selected housekeeping genes (carB, clpX, dnaA, groEL, murE, pyrG, pheS, recA, rpoC, and uvrC). All 229 isolates could be allocated to 171 unique sequence types, including 25 clonal complexes and 71 singletons. The high index of association value (1.3524) and standardized index of association value (0.1503) indicate the formation of an underlying clonal population by all the isolates. However, split-decomposition, relative frequency of occurrence of recombination and mutation, and relative effect of recombination and mutation in the diversification values confirm that recombination may have occurred, and were more frequent than mutation during the evolution of Lb. casei. Results from Structure analyses (version 2.3; http://pritch.bsd.uchicago.edu/structure.html) demonstrated that there were 5 lineages in the Lb. casei isolates, and the overall relatedness built by minimum spanning tree showed no clear relationship between the clonal complexes with either the isolation sources or sampling locations of the isolates. Our newly developed MLST scheme of Lb. casei was an easy and valuable tool that, together with the construction of an MLST database, will contribute to further detailed studies on the evolution and population genetics of Lb. casei from various niches. PMID- 27179868 TI - Cabergoline inhibits prolactin secretion and accelerates involution in dairy cows after dry-off. AB - Dairy cattle require a dry period between successive lactations to ensure optimal milk production. Because prolactin (PRL) is necessary for the initiation and maintenance of milk production, strategies that can inhibit PRL secretion might hasten the involution process. The objective of this study was to determine the effect of the PRL release inhibitor cabergoline on markers of mammary gland involution during the early dry period. To assess the effect of cabergoline treatment on mammary gland involution, 14 Holstein dairy cows in late lactation were treated with either a single i.m. administration of 5.6mg of cabergoline (Velactis, Ceva Sante Animale, Libourne, France, n=7) or placebo (n=7) at the time of dry-off. Blood samples and mammary secretion samples were collected 6d before dry-off and again 1, 2, 3, 4, 8, and 14d following the abrupt cessation of lactation. Blood samples were used to determine plasma PRL concentrations. Mammary secretion samples were used to determine somatic cell count, milk fat, lactose, true protein content, and concentrations of alpha-lactalbumin, lactoferrin, and citrate. Following the cessation of lactation, changes in mammary secretion composition indicated diminished milk synthesis, including reduced concentrations of alpha-lactalbumin, citrate, and lactose. In contrast, milk somatic cell count, percent total protein, percent fat content, and lactoferrin concentrations significantly increased as involution progressed. Cabergoline treatment decreased the plasma PRL concentrations during the first week of dry-off, compared with the control treatment. No significant differences in citrate, alpha-lactalbumin, or protein content were observed between treatment groups. The most dramatic changes in secretion composition as a consequence of cabergoline treatment occurred during the first week of the dry period, when lactose concentrations and the citrate:lactoferrin molar ratio were lower and lactoferrin concentrations higher than in the control cows. Cabergoline treatment also tended to increase fat content and somatic cell count more rapidly following dry-off compared with the control group. These changes in mammary secretion composition following the abrupt cessation of lactation indicate that cabergoline treatment facilitated dry-off and effectively accelerated mammary gland involution. PMID- 27179869 TI - Short communication: Association of milk fatty acids with early lactation hyperketonemia and elevated concentration of nonesterified fatty acids. AB - The objective of our study was to extend the limited research available on the association between concentrations of milk fatty acids and elevated nonesterified fatty acids (NEFA) and beta-hydroxybutyrate (BHB) concentrations in early lactation dairy cattle. Measurement of milk fatty acids for detection of cows in excessive negative energy balance has the potential to be incorporated in routine in-line monitoring systems. Blood samples were taken from 84 cows in second or greater lactation 3 times per week between 3 to 14 d in milk. Cows were characterized as hyperketonemic (HYK) if blood BHB concentration was >=1.2mmol/L at least once and characterized as having elevated concentrations of NEFA (NEFAH) if serum NEFA concentration was >=1mmol/L at least once. Composition of colostrum and milk fatty acids at wk 2 postpartum was used to investigate the potential diagnostic value of individual fatty acids and fatty acid ratios for the correct classification of cows with NEFA and BHB concentrations above these thresholds, respectively. Receiver operating characteristic (ROC) curves were used to identify thresholds of fatty acid concentration and fatty acid ratios when ROC area under the curve was >=0.70. Correct classification rate (CCR, %) was calculated as {[(number of true positives + number of true negatives)/total number tested] * 100}. None of the colostrum fatty acids yielded a sufficiently high area under the curve in ROC analysis for the association with HYK and NEFAH. The following fatty acids and fatty acid ratios were identified for an association with NEFAH (threshold, CCR): C15:0 (<=0.65g/100g, 68.3%); cis-9 C16:1 (>=1.85g/100g, 70.7%); cis-9 C18:1 (>=26g/100g, 69.5%), cis-9 C18:1 to C15:0 ratio (>=45, 69.5%); cis-9 C16:1 to C15:0 (>=2.50, 73.2%). Several fatty acids were associated with HYK (threshold, CCR): C6:0 (<=1.68g/100g, 80.5%), C8:0 (<=0.80g/100g, 80.5%), C10:0 (<=1.6g/100g, 79.3%); C12:0 (<=1.42g/100g, 82.9%); C14:0 (<=6.10g/100g, 84.1%); C15:0 (<=0.50g/100g, 82.9%), cis-9 C18:1 (>=30g/100g, 81.7%). The use of fatty acid ratios did not improve CCR over using individual fatty acids for the classification of HYK. Colostrum fatty acid composition was not useful in predicting NEFAH or HYK between 3 to 14 d in milk. Accuracy of milk fatty acids and fatty acid ratios to correctly classify cows with elevated concentrations of NEFA and BHB between 3 to 14 d in milk was moderate and overall higher for HYK. Determining changes in the fatty acid composition of milk fat from milk samples at wk 2 postpartum for the detection of cows with elevated concentrations of BHB and NEFA can currently not be recommended to replace direct measurement. Future applications should target repeated milk sampling between 3 to 14 d in milk to identify the best sampling for determination of milk fatty acid composition within the first 2 wk postpartum. PMID- 27179870 TI - Repeated intrauterine infusions of lipopolysaccharide alter gene expression and lifespan of the bovine corpus luteum. AB - Inflammation of the uterus is associated with disturbed ovarian function and reduced reproductive performance in dairy cows. To investigate the influence of endometritis on the bovine corpus luteum, 8 heifers received intrauterine infusions with either phosphate-buffered saline (PBS; 9mL) or Escherichia coli lipopolysaccharide (LPS; 3ug/kg of body weight diluted in 9mL of PBS) at 6-h intervals from 12h before and until 9d after ovulation during 2 cycles in a random order (ovulation=d 1). An untreated cycle was examined before and after PBS and LPS cycles, and the mean values from both untreated cycles were used as control. In all cycles, blood sampling and ultrasonography of the ovaries were performed on d 0, 1, 2, 4, 6, 8, 9, 10, 12, 15, 18, and then every 2d until ovulation. Endometrial cells were collected for cytology and quantitative real time reverse transcriptase PCR on d 0, 6, and 9, and on d 0 and 6, respectively, and luteal tissue was collected for quantitative real-time reverse transcriptase PCR on d 6 and 9. Both, PBS and LPS infusions induced subclinical endometritis, which was accompanied by increased endometrial mRNA abundance of proinflammatory cytokines IL1beta, IL8, and tumor necrosis factor alpha. Additionally, LPS challenge induced premature luteolysis, which was characterized by increased plasma concentrations of PGF2alpha metabolite, decreased plasma progesterone concentrations, and reduced luteal size and blood flow compared with the control. The luteal mRNA expression of the LPS receptor TLR4, PGE synthase, and the apoptosis-related factor CASP3 were higher, and those of steroidogenic factors STAR and HSD3B, the PGF receptor, and the angiogenic factor VEGFA121 were lower after LPS challenge compared with the control. In conclusion, repeated intrauterine LPS infusions during the first 9d of the estrous cycle alter gene expression and shorten the lifespan of the bovine corpus luteum. PMID- 27179871 TI - Evaluation of ear skin temperature as a cow-side test to predict postpartum calcium status in dairy cows. AB - Subclinical hypocalcemia is considered a gateway disease that increases susceptibility to other metabolic and infectious diseases in transition dairy cows. In the absence of a cow-side test, however, it is difficult to identify hypocalcemic cows. The objective of this study was to evaluate ear skin temperature as a diagnostic predictor of serum calcium concentration. We conducted a cross-sectional study on 7 commercial dairy farms, involving 251 cows 0 to 48h after calving. Skin temperature of the ears (STEar) was scored manually by palpating both ears. An infrared thermometer was used to measure ear temperature, skin temperature on the coxal tuber (STCox), and ambient temperature. Rectal temperature was measured using a digital thermometer. A blood sample was drawn to determine serum calcium concentration. Hypocalcemia was defined as serum calcium below 2.0mmol/L, irrespective of clinical symptoms. Serum calcium concentration <2.0mmol/L in connection with clinical symptoms was defined as clinical milk fever; serum calcium concentration <2.0mmol/L without clinical symptoms was defined as subclinical hypocalcemia. Multivariate analysis using the GENLINMIXED procedure and receiver operating characteristic analysis were performed to evaluate whether serum calcium concentration could be predicted using ear temperature and other temperature estimates. The prevalence of hypocalcemia was 3.3, 27.3, 32.8, and 69.6% for cows in first, second, third, and fourth or greater lactation, respectively. None of the cows in first and second lactation had clinical milk fever. The prevalence of clinical milk fever was 6.0 and 20.3% for cows in their third and fourth or greater lactation, respectively. A decrease in ear temperature of 0.39 degrees C [95% confidence interval (CI): 0.25-0.54] was associated with a decrease of 0.1mmol/L in serum calcium concentration. Ambient temperature, however, was a major confounder for ear temperature. With an increase in ambient temperature of 1 degrees C, STEar rose by 0.78 degrees C (95% CI: 0.67-0.90). Hypothermia was more pronounced in clinical milk fever (median 21.8 degrees C; interquartile range 14.7-27.0 degrees C) compared with subclinical hypocalcemia (median 27.6 degrees C, interquartile range 22.1-30.8 degrees C). All temperature estimates had only accurate test characteristics based on their area under the curve for prediction of subclinical hypocalcemia (area under the curve for STEar, STCox, and rectal temperature were 0.641, 0.668, and 0.606, respectively) when cows with clinical milk fever were excluded. Although ear temperature has been associated with serum calcium concentration, ear temperature cannot be recommended for diagnosis of subclinical hypocalcemia. PMID- 27179872 TI - Estimation of economic values for milk coagulation properties in Italian Holstein Friesian cattle. AB - The economic values (EV) of production traits, rennet coagulation time (RCT, min), and curd firmness (a30, mm) were derived for Italian Holstein-Friesian dairy cattle, based on the Grana Padano cheese industry. Three different sets of EV for RCT and a30 were estimated, assuming +2.5% (scenario 1), +5% (scenario 2), and +10% (scenario 3) increment in cheese yield due to the effect of milk coagulation properties (MCP). A model was developed to simulate the transformation of milk into Grana Padano cheese. The EV of RCT and a30 were ?2.213, -?4.426, and -?8.852/min, and ?0.877, ?1.755, and ?3.509/mm for scenarios 1, 2, and 3, respectively. Relative emphasis of traits in the breeding objectives of the Italian Holstein-Friesian dairy cattle population should account for the effect of MCP on cheese yield. Economic values for milk components and MCP were affected by changes of dairy products, whereas variations of feed prices did not influence EV of RCT and a30. PMID- 27179874 TI - Technical note: Bayesian calibration of dynamic ruminant nutrition models. AB - Mechanistic models of ruminant digestion and metabolism have advanced our understanding of the processes underlying ruminant animal physiology. Deterministic modeling practices ignore the inherent variation within and among individual animals and thus have no way to assess how sources of error influence model outputs. We introduce Bayesian calibration of mathematical models to address the need for robust mechanistic modeling tools that can accommodate error analysis by remaining within the bounds of data-based parameter estimation. For the purpose of prediction, the Bayesian approach generates a posterior predictive distribution that represents the current estimate of the value of the response variable, taking into account both the uncertainty about the parameters and model residual variability. Predictions are expressed as probability distributions, thereby conveying significantly more information than point estimates in regard to uncertainty. Our study illustrates some of the technical advantages of Bayesian calibration and discusses the future perspectives in the context of animal nutrition modeling. PMID- 27179873 TI - Parturition in dairy cows temporarily alters the expression of genes in circulating neutrophils. AB - Extensive metabolic and physiologic changes occur during the peripartum, concurrent with a high incidence of infectious disease. Immune dysfunction is a likely contributor to the increased risk of disease at this time. Studies using high-yielding, total mixed ration-fed cows have indicated that neutrophil function is perturbed over the transition period; however, this reported dysfunction has yet to be investigated in moderate-yielding, grazing dairy cows. Therefore, we investigated changes in the expression of genes involved in neutrophil function. Blood was collected from cows at 5 time points over the transition period: precalving (-1wk; n=46), day of calving (d 0; n=46), and postcalving at wk 1 (n=46), wk 2 (n=45), and wk 4 (n=43). Neutrophils were isolated by differential centrifugation and gene expression was investigated. Quantitative reverse transcriptase PCR with custom-designed primer pairs and Roche Universal Probe Library (Roche, Basel, Switzerland) chemistry, combined with microfluidics integrated fluidic circuit chips (96.96 Dynamic Array, San Francisco, CA) were used to investigate the expression of 78 genes involved in neutrophil function and 18 endogenous control genes. Statistical significance between time points was determined using a repeated measures ANOVA. Genes that were differentially expressed over the transition period included those involved in neutrophil adhesion (SELL, ITGB2, and ITGBX), mediation of the immune response (TLR4, HLA-DRA, and CXCR2), maturation, cell cycle progression, apoptosis (MCL1, BCL2, FASLG, and RIPK1), and control of gene expression (PPARG, PPARD, and STAT3). We noted reduced gene expression of proinflammatory cytokines (IFNG, TNF, IL12, and CCL2) on the day of calving, whereas anti-inflammatory cytokine gene expression (IL10) was upregulated. Increased gene expression of antimicrobial peptides (BNBD4, DEFB10, and DEFB1) occurred on the day of calving. Collectively, transcription profiles are indicative of functional changes in neutrophils of grazing dairy cows over the transition period and align with studies in cows of conventional total mixed ration systems. This altered function may predispose cows to disease over the transition period and is likely to be a natural change in function due to parturition. PMID- 27179875 TI - Secretion of glucagon-like peptide-2 responds to nutrient intake but not glucose provision in milk-fed calves. AB - Glucagon-like peptide 2 (GLP-2) is a peptide released by the lower gut that has potent trophic and restorative effects on the intestinal epithelium. Two experiments were conducted to assess the effects of feeding rate and either metabolizable or nonmetabolizable glucose supplementation on GLP-2 concentrations in plasma and intestinal development in Holstein calves. In the first experiment, 48 newborn calves were assigned to 12 treatments (n=4) corresponding to the factorial combination of 4 milk feeding amounts [1.75, 1.32, 0.88, and 0.44% of body weight (BW) as dry matter (DM)] and 3 oral supplementation treatments (nonsupplemented, glucose-supplemented, and 3-O-methyl glucose-supplemented). In the second experiment 30 newborn calves (n=10) were fed milk at a fixed rate of 1.75% of BW as DM and assigned to the same glucose supplementation treatments used in experiment 1 to investigate effects on intestinal development. In the first experiment, we found a saturating response of plasma GLP-2 to increasing feeding levels. The feeding rate at which 50% of the maximal GLP-2 release occurred was estimated to be 0.53% of BW as DM or 30.3% of the maximum feeding rate (1.75% of BW as DM), whereas maximal secretion was estimated to be about 98.6 pmol/L. In turn, feeding 75, 50, or 25% of the maximal feeding rate (i.e., 1.75% BW as DM) resulted in plasma GLP-2 concentrations 87, 72, and 49% of that in fully fed calves, respectively. Neither metabolizable nor nonmetabolizable glucose supplementation affected GLP-2 secretion and no interaction with feed intake level was detected. In the second experiment, no effect of glucose supplementation was observed on intestinal growth, mucosal cell proliferation, or expression of genes related to the actions of GLP-2. Nonetheless, we observed that a pool of genes of the GLP-2 signaling pathway was more abundantly and coordinately regulated in the colon than in the ileum of these animals, indicating an opportunity for dietary induction of the peptide in this organ. In conclusion, during this experiment, plasma GLP-2 concentrations responded in a diminishing return fashion to milk intake but not to glucose supplementation, even at milk consumption levels of only 0.4% of BW as DM. PMID- 27179876 TI - Public and farmer perceptions of dairy cattle welfare in the United States. AB - This research used surveys of the public and dairy farmers in the United States to assess perceptions and attitudes related to dairy cattle welfare. Sixty-three percent of public respondents indicated that they were concerned about dairy cattle welfare. Most public respondents agreed that animal welfare was more important than low milk prices but that the average American did not necessarily agree. Most public respondents had not viewed media stories related to dairy cattle welfare. Respondents who had viewed these stories did so on television or Internet. The United States Department of Agriculture (USDA) was viewed as the most accurate source of information related to dairy cattle welfare, followed by the Humane Society of the United States (HSUS) and the American Veterinary Medicine Association (AVMA). Both public and dairy farmer respondents viewed farmers as having the most influence on dairy cattle welfare. However, there was a general pattern of public respondents indicating that groups including USDA, HSUS, and AVMA had a relatively larger influence on dairy cattle welfare than did farmer respondents. In contrast, dairy farmers indicated that individual actors farmers, veterinarians, consumers-had more influence than the public indicated. When asked about production practices, most public respondents indicated that they would vote for a ban on antibiotic use outside of disease treatment or for the mandated use of pain control in castration. However, a minority indicated they would vote to ban the use of recombinant bovine somatotropin (rbST) or to pay a premium for milk produced without rbST. With respect to explaining public support for the production practice bans and limits, respondents were more likely to vote for the restrictions if they were older, female, had higher income, or had viewed animal welfare stories in the media. PMID- 27179877 TI - Short communication: Test for nonpregnancy in dairy cows based on plasma progesterone concentrations before and after timed artificial insemination. AB - Timed artificial insemination (AI) programs have increased reproductive efficiency in dairy herds. A low timed AI pregnancy per AI is partially explained by cows that fail to respond optimally to the series of treatments that are designed to synchronize ovulation for AI. We hypothesized that testing cows for plasma progesterone concentrations during a timed AI protocol could be used as an early diagnostic test for nonpregnancy. Lactating Holstein cows (n=160) in 2 confinement-style dairies were used. Cows were treated with Presynch Ovsynch 56 for timed AI. Concentrations of progesterone in plasma were measured at -3, 0, 7, and 25 d relative to timed AI. Progesterone data were analyzed and receiver operating characteristic curves were generated by using logistic regression. The area under the receiver operating curves for a progesterone test for nonpregnancy on d -3 (PGF2alpha), 0 (AI), 7, and 25 d relative to timed AI were 0.68, 0.52, 0.55, and 0.89, respectively. The cutpoints and sensitivity (respectively) for the progesterone test were 0.51ng/mL (lower=nonpregnant) and 28.2% for the day of PGF2alpha, 0.43ng/mL (greater=nonpregnant) and 17.9% for the day of AI, 1.82ng/mL (lower=nonpregnant) and 23.1% for 7 d after AI, and 2.67ng/mL (lower=nonpregnant) and 76.0% for 25 d after AI. The false positive rate was less than 5% for all tests. Analysis of a second data set from a published study gave approximately the same cutpoints and sensitivity. When both studies were combined, approximately 20% of nonpregnant cows could be identified with a single test that was done before or shortly after AI with a false positive rate of less than 5%. When 2 and 3 tests were applied sequentially, the sensitivity for identifying nonpregnant cows increased from 38.4 to 50.5%. The pregnancy per AI for those cows that met the established progesterone criteria was approximately 3 to 4 times greater than those that failed to meet the criteria. The conclusions were that cows destined to be nonpregnant after timed AI can be identified before or shortly after AI. Testing for nonpregnancy before or shortly after AI may have utility with respect to eliminating a nonproductive AI (cows identified before AI) or shortening the time to reinsemination (cows identified by 1 wk after AI). PMID- 27179878 TI - Assessment of an application for touchscreen devices to record calving-related events in dairy herds and monitor personnel performance. AB - The objectives of the present study were to assess (1) the effectiveness of a calving training workshop and an application (app) for touchscreen devices to capture calving-related events, and (2) personnel compliance with calving protocols (time from birth to feeding of first colostrum and time that cows spent in labor). Calving personnel (n=23) from 5 large dairy farms (range: 800-10,000 cows) participated in the study. Participants received training through an on farm workshop regarding calving management practices and functioning of the app before recording calving-related events. Pre- and posttest evaluations were administered to each participant to measure their knowledge gain and satisfaction with the workshop. Calving personnel recorded calving-related events (n=323) using the app for 7 d following training. Furthermore, the records collected with the app were used to assess missing and incorrect data and calving personnel compliance with calving management protocols (recording time that cows spent in labor and timing of feeding first colostrum to calves). Calving personnel reported that the information provided during the training was relevant (agree=14.3% and strongly agree=85.7%) and of great immediate use (agree=33.3% and strongly agree=66.7%). The presented materials and hands-on demonstrations substantially increased the knowledge level of the attendees (by 23.7 percentage points from pre- to posttest scores). The follow-up assessment with participants revealed that the app was easy to use (91.3%) and that they would continue to use it (100%). Frequency of incorrect (r=0.77) or missing (r=0.76) data was positively correlated with calving:personnel ratio. Furthermore, calving personnel compliance with calving protocols was significantly different within and between herds. These results substantiated the great variation in compliance with calving management protocols within and between dairy farms. Furthermore, the app may serve as a tool to monitor personnel compliance with first feeding of colostrum to calves and their awareness and recognition of amount of time that each cow spent in labor. This would allow decision-makers to adjust, reassign tasks, or plan the management according to actual calving rate to improve the overall quality of data (frequency of incorrect and missing data) and calf welfare (survival and performance). PMID- 27179879 TI - Identifying variations in adherence to the CDC sexually transmitted disease treatment guidelines of Neisseria gonorrhoeae. AB - OBJECTIVE: Neisseria gonorrhoeae is identified as a national challenge due to emerging antimicrobial resistance. The Centers for Disease Control and Prevention (CDC) sexually transmitted diseases (STD) Treatment guidelines are updated to address emerging concerns. The aims of this study were 1) to determine the proportion of cases that were adherent to two aspects of the treatment guidelines: antimicrobial treatment and follow-up recommendations and 2) to evaluate differences in adherence based on clinical location. STUDY DESIGN: A retrospective review of medical records was performed for the first positive N. gonorrhoeae tests identified in subjects between May 2011 and December 2013 at a large urban academic medical centre. We hypothesised that provider adherence to STD treatment and prevention guidelines was better at STD specialised clinics than non-specialised settings. METHODS: Adherence to CDC STD treatment guidelines was determined for both treatment and prevention management. Demographic, testing differences, and appropriate treatment and follow-up between speciality and non speciality clinics were evaluated using chi-squared, Fisher's exact, and Student's t-test, when appropriate. RESULTS: During the study period, 542/714 positive tests were analysed. Healthcare provider adherence to antimicrobial management guidelines was 82% during the study period. Adherence to the guidelines was 76% and 88% for the 2010 and 2012 time periods, respectively. Non adherence to recommendations included lack of dual therapy for N. gonorrhoeae in speciality clinics and incorrect dose in non-speciality clinics. Appropriate preventive follow-up was identified in only 31% of cases. Both speciality clinics and non-speciality clinics had errors related to partner therapy. CONCLUSIONS: Providers in speciality clinics were more adherent to the guidelines compared with providers at other clinical sites. Significant lack of adherence was identified in the follow-up management of N. gonorrhoeae. Evaluation of treatment errors may help improve medical management of N. gonorrhoeae. PMID- 27179880 TI - Expansion of the neuropeptidome of the globally invasive marine crab Carcinus maenas. AB - Carcinus maenas is widely recognized as one of the world's most successful marine invasive species; its success as an invader is due largely to its ability to thrive under varied environmental conditions. The physiological/behavioral control systems that allow C. maenas to adapt to new environments are undoubtedly under hormonal control, the largest single class of hormones being peptides. While numerous studies have focused on identifying native C. maenas peptides, none has taken advantage of mining transcriptome shotgun assembly (TSA) sequence data, a strategy proven highly successful for peptide discovery in other crustaceans. Here, a C. maenas peptidome was predicted via in silico transcriptome mining. Thirty-seven peptide families were searched for in the extant TSA database, with transcripts encoding precursors for 29 groups identified. The pre/preprohormones deduced from the identified sequences allowed for the prediction of 263 distinct mature peptides, 193 of which are new discoveries for C. maenas. The predicted peptides include isoforms of adipokinetic hormone-corazonin-like peptide, allatostatin A, allatostatin B, allatostatin C, bursicon, CCHamide, corazonin, crustacean cardioactive peptide, crustacean hyperglycemic hormone, diuretic hormone 31, diuretic hormone 44, eclosion hormone, FMRFamide-like peptide, HIGSLYRamide, intocin, leucokinin, myosuppressin, neuroparsin, neuropeptide F, orcokinin, pigment dispersing hormone, proctolin, pyrokinin, red pigment concentrating hormone, RYamide, short neuropeptide F, SIFamide, and tachykinin-related peptide. This peptidome is the largest predicted from any single crustacean using the in silico approach, and provides a platform for investigating peptidergic signaling in C. maenas, including control of the processes that allow for its success as a global marine invader. PMID- 27179881 TI - Melatonin biosynthesizing enzyme genes and clock genes in ovary and whole brain of zebrafish (Danio rerio): Differential expression and a possible interplay. AB - The present study on zebrafish (Danio rerio) is the first attempt to demonstrate the circadian mRNA expression of melatonin biosynthesizing enzyme genes (Tph1a, Aanat1, Aanat2 and Hiomt) and clock associated genes (Bmal1a, Clock1a, Per1b, Per2 and Cry2a) in the ovary with a comparison to whole brain in normal (LD=12h L:12h D) and altered photic conditions (continuous dark, DD; continuous light, LL). Moreover, the present study also confirmed the ability of zebrafish ovary to biosynthesize melatonin both in vivo and in vitro with a significant difference at day and night. qRT-PCR analysis of genes revealed a dark acrophase of Aanat2 in both organs while Tph1 is in whole brain in LD condition. On the contrary, Bmal1a and Clock1a giving their peak in light, thereby showing a negative correlation with Tph1a and Aanat2. In LD-ovary, the acrophase of Tph1a, Bmal1a and Clock1a is in light and thus display a positive correlation. This trend of relationship in respect to Tph1a is not changing in altered photic conditions in both organs (except in DD-ovary). On the other hand this association for Aanat2 is varying in ovary under altered photic conditions but only in DD-whole brain. Both in LD and LL the expression of Aanat2 in brain presenting an opposite acrophase with both Bmal1a and Clock1a of ovary and consequently displaying a strong negative correlation among them. Interestingly, all ovarian clock associated genes become totally arrhythmic in DD, representing a loss of correlation between the melatonin synthesizing genes in brain and clock associated genes in ovary. The result is also indicating the formation of two heterodimers namely Clock1a:Bmal1a and Per2:Cry2a in the functioning of clock genes in both organs, irrespective of photic conditions, as they are exhibiting a strong significant positive correlation. Collectively, our data suggest that ovary of zebrafish is working as peripheral oscillator having its own melatonin biosynthesizing machinery and signifying a possible correlation with central oscillating system in various photic conditions. PMID- 27179882 TI - Molecular cloning of motilin and mechanism of motilin-induced gastrointestinal motility in Japanese quail. AB - Motilin, a peptide hormone produced in the upper intestinal mucosa, plays an important role in the regulation of gastrointestinal (GI) motility. In the present study, we first determined the cDNA and amino acid sequences of motilin in the Japanese quail and studied the distribution of motilin-producing cells in the gastrointestinal tract. We also examined the motilin-induced contractile properties of quail GI tracts using an in vitro organ bath, and then elucidated the mechanisms of motilin-induced contraction in the proventriculus and duodenum of the quail. Mature quail motilin was composed of 22 amino acid residues, which showed high homology with chicken (95.4%), human (72.7%), and dog (72.7%) motilin. Immunohistochemical analysis showed that motilin-immunopositive cells were present in the mucosal layer of the duodenum (23.4+/-4.6cells/mm(2)), jejunum (15.2+/-0.8cells/mm(2)), and ileum (2.5+/-0.7cells/mm(2)), but were not observed in the crop, proventriculus, and colon. In the organ bath study, chicken motilin induced dose-dependent contraction in the proventriculus and small intestine. On the other hand, chicken ghrelin had no effect on contraction in the GI tract. Motilin-induced contraction in the duodenum was not inhibited by atropine, hexamethonium, ritanserin, ondansetron, or tetrodotoxin. However, motilin-induced contractions in the proventriculus were significantly inhibited by atropine and tetrodotoxin. These results suggest that motilin is the major stimulant of GI contraction in quail, as it is in mammals and the site of action of motilin is different between small intestine and proventriculus. PMID- 27179883 TI - Dominance-related seasonal song production is unrelated to circulating testosterone in a subtropical songbird. AB - Circulating testosterone (T) is widely considered to play a key role in the production of sexual displays by male vertebrates. While numerous studies support a role for circulating T in promoting the production of song in male birds, this understanding is based primarily on evidence from seasonally breeding northern temperate species, leaving it unclear whether this mechanism generalizes to other regions of the world. Here we investigate whether variation in circulating levels of T can explain the marked within- and among-individual variation in male song performance observed in a subtropical population of the year-round territorial white-browed sparrow weaver (Plocepasser mahali mahali). Our findings reveal that both circulating T and male song production peaked at a similar time point, halfway through the population-level breeding season. However, while dominant males were more likely to sing and sang for longer than subordinate males, within group paired comparisons revealed no dominance-related differences in circulating T. Moreover, comparisons both among and within individual dominant males revealed that song duration, syllable rate and proportion of time spent singing were all unrelated to circulating T. Together, our findings suggest that natural variation in male song production, at least in this population of white-browed sparrow weavers, is achieved principally through mechanisms other than variation in circulating T concentration. More widely, our results are in line with the view that male song production is not exclusively regulated by gonadally synthesized steroids. PMID- 27179884 TI - Moult-inhibiting fusion protein augments while polyclonal antisera attenuate moult stages and duration in Penaeus monodon. AB - Moulting in crustaceans is regulated by moult-inhibiting hormone (MIH) of the CHH family neuropeptides. The inhibitory functions of MIH have pivotal roles in growth and reproduction of Penaeus monodon. In this study, we report the expression of a thioredoxin-fused mature MIH I protein (mf-PmMIH I) of P. monodon in a bacterial system and its use as antigen to raise polyclonal antiserum (anti mf-PmMIH I). The mature MIH I gene of 231bp, that codes for 77 amino acids, was cloned into the Escherichia coli thioredoxin gene fusion expression system. The translation expression vector construct (mf-PmMIH I+pET32a+) upon induction produced 29.85kDa mature MIH I fusion protein (mf-PmMIH I). The purified fusion protein was used as exogenous MIH I and as antigen to raise polyclonal antisera. When fusion protein (mf-PmMIH I) was injected into D2 and D3 stages of juvenile shrimp, the moult cycle duration was extended significantly to 16.67+/-1.03 and 14.67+/-1.03days respectively compared to that of 11.67+/-1.03days in controls. Moult duration was further reduced to 8.33+/-0.82days when polyclonal antiserum (anti-mf-PmMIH I - 1:500 dilutions) was injected. Anti-mf-PmMIH I immunolocalized MIH I producing neurosecretory cells in the eyestalk of P. monodon. In short, the present manuscript reports an innovative means of moult regulation in P. monodon with thioredoxin fused MIH I and antisera developed. PMID- 27179885 TI - Neuroendocrine control of ionic balance in zebrafish. AB - Zebrafish (Danio rerio) is an emerging model for integrative physiological research. In this mini-review, we discuss recent advances in the neuroendocrine control of ionic balance in this species, and identify current knowledge gaps and issues that would benefit from further investigation. Zebrafish inhabit a hypo ionic environment and therefore are challenged by a continual loss of ions to the water. To maintain ionic homeostasis, they must actively take up ions from the water and reduce passive ion loss. The adult gill or the skin of larvae are the primary sites of ionic regulation. Current models for the uptake of major ions in zebrafish incorporate at least three types of ion transporting cells (also called ionocytes); H(+)-ATPase-rich cells for Na(+) uptake, Na(+)/K(+)-ATPase-rich cells for Ca(2+) uptake, and Na(+)/Cl(-)-cotransporter expressing cells for both Na(+) and Cl(-) uptake. The precise molecular mechanisms regulating the paracellular loss of ions remain largely unknown. However, epithelial tight junction proteins, including claudins, are thought to play a critical role in reducing ion losses to the surrounding water. Using the zebrafish model, several key neuroendocrine factors were identified as regulators of epithelial ion movement, including the catecholamines (adrenaline and noradrenaline), cortisol, the renin-angiotensin system, parathyroid hormone and prolactin. Increasing evidence also suggests that gasotransmitters, such as H2S, are involved in regulating ion uptake. PMID- 27179886 TI - Delayed recurrence of acute retinal necrosis (ARN): A case series. AB - PURPOSE: To report five cases of acute retinal necrosis (ARN) that reactivated in the same eye or presented in the contralateral eye between two and nineteen years after the initial episode of acute retinal necrosis. CASES: Five patients with a previous history of ARN developed recurrent ARN infection following a lengthy latency period. In all five patients who initially presented with unilateral disease, four developed infection in the contralateral eye and one developed recurrent infection in the ipsilateral eye. Latency periods ranged from two to nineteen years, and final visual acuity in the affected eyes ranged from 20/30 to no light perception. Each patient was treated with antiviral medication for both the initial infection and for subsequent reactivations, but was not on long-term prophylaxis at the time of recurrent disease. CONCLUSION: Although rare, delayed onset reactivation of ARN can occur in either the same eye or contralateral eye despite adequate treatment. While contralateral spread of initial infection is fairly common, these reactivations rarely occur more than six weeks after initial infection. Currently there are no guidelines for use of prophylactic antiviral medication to prevent late recurrence of ARN. PMID- 27179887 TI - Can breast cancer register data on recommended adjuvant treatment be used as a proxy for actually given treatment? AB - PURPOSES: To study agreement between recommended adjuvant treatment after primary breast cancer (BC) surgery from the clinical based National Breast Cancer Register and initiated adjuvant treatment from medical records; factors associated with agreement; and reasons for discontinuation or change of planned treatment. METHOD: Included were 970 women who had undergone BC surgery, aged 20 63 years, living in Stockholm County, and literate in Swedish. EXCLUSION CRITERIA: Distant metastases, pre-surgical chemotherapy, and/or a previous BC diagnosis. Information on clinical tumor stage, surgical treatment, recommended adjuvant radiotherapy, chemotherapy, and endocrine therapy was obtained from the BC register. Type of initiated adjuvant treatments, if treatment plan was followed, and reasons for discontinuation were extracted from medical records. RESULTS: The register had high completeness and agreement was high, 94-96%, (kappa 0.801-0.908) for all types of treatment. Disagreement regarding radiotherapy and chemotherapy was associated with having >=1 lymph node metastases and more extended axillary surgery, and for radiotherapy also more extended breast surgery. There were no such associations with age, tumor size, or invasiveness. None of these factors were associated with disagreement regarding recommended versus initiated endocrine therapy. Endocrine therapy was most often discontinued (24%), mostly due to toxicity which was also the most common reason for discontinuation of chemotherapy. CONCLUSIONS: Swedish register data on recommended treatment has high validity in women aged 24-63 years, with limited BC, and demonstrates utility as a proxy for initiated treatment in this group. This is of interest since extracting data from medical records is resource demanding. PMID- 27179888 TI - Development and validation of scales for attitudes, self-reported practices, difficulties and knowledge among home care nurses providing palliative care. AB - PURPOSE: Although educational programs for nurses are required to ensure high quality home care, there is currently no scale to appropriately evaluate such programs for home care nurses providing palliative care. We developed and validated four scales to evaluate home care nurses' attitude, self-reported practices, difficulties, and knowledge regarding home palliative cancer care, and identified factors associated with home care nurses' attitude, self-reported practices, and difficulties. METHOD: The scale items were generated based on literature review and a cross-sectional questionnaire survey was conducted. Experienced home care nurses from visiting nurse stations who enrolled in a home palliative care educational program were recruited for this survey. RESULTS: Of the 125 questionnaires delivered to home care nurses, 122 were returned (response rate, 98%). After factor analysis, the scale for attitude comprised four domains with 12 items, the scale for self-reported practices comprised six domains with 26 items, and the scale for difficulties comprised five domains with 18 items. Cronbach's alphas for these scales were 0.61-0.70. After using the Item Response Theory model, the scale for knowledge was found to comprise 26 items. The multiple logistic regression model showed that experience in caring for terminal patients at home or in hospitals were associated with having more positive attitude, higher self-reported practices and lower difficulties. CONCLUSIONS: We developed valid and reliable scales to evaluate home care nurses' attitude, self reported practices, difficulties, and knowledge regarding home palliative cancer care. These scales potentially useful for evaluating a home palliative cancer care education program for nurses. PMID- 27179889 TI - A gap between the intention of the Swedish law and interactions between nurses and children of patients in the field of palliative oncology - The perspective of nurses. AB - PURPOSE: Children who have a parent with incurable cancer are in a vulnerable situation and the Swedish law tries to protect them. This article aims to explore the interactions between nurses and children of patients with incurable cancer from the nurses' perspective. METHOD: Semi-structured interviews with nine nurses in palliative oncology in Southern Sweden. Latent content analysis was carried out, inspired by Lundmann and Graneheim. RESULTS: Parents are gatekeepers to the children's involvement and meetings with the healthcare professionals. Therefore the nurses were dependent on the parents for contact with their children. Additionally, nurses were subject to the structural frame of their working environment in terms of time, economy, resources and the medical logic ruling the priorities for nursing during their daily working day. The opportunities to pay attention to the children of patients were limited, despite good intentions, willingness and a favourable legal framework. Teenagers were regarded as a challenge, and per se they challenged the nurses' opportunities to gain control of the meetings and situations around the families. CONCLUSIONS: Often nurses did not see and acknowledge the children of the palliative patient. They knew that the children were there and that it was important that they were there, but they challenged the order in the working environment in relation to time-allocated tasks and working flow. In the working environment patients were prioritised over relatives. From the perspective of nurses, there is a gap between the intentions of the Swedish law and the interactions between nurses and children. PMID- 27179890 TI - Prevalence and predictors of distress in women taking part in surgical continuity of care for breast cancer: A cohort study. AB - PURPOSE: Women with breast cancer often experience distress. This cohort study investigated the prevalence of distress, predictors of distress, and changes in distress during surgical continuity of care for breast cancer (from diagnosis to commencement of adjuvant treatment). METHODS: The participants were 1079 women with breast cancer who were recruited between April 2013 and May 2014 from 11 breast surgery departments in Denmark. Distress was evaluated using the Distress Thermometer (DT) and predictors of distress were assessed with a self administered questionnaire at the time of diagnosis (T1), at discharge (T2), and by the start of adjuvant treatment or follow-up (T3). Repeated measures ANOVA, simple and multiple linear regression, and mixed effects regression models were used to identify predictors and estimate changes in distress. RESULTS: At T1, 249 (24.3%) women reported no or minimal distress, 298 (29.1%) moderate distress, and 407 (39.8%) severe distress. The mean distress was 5.5 points on the DT, which decreased by 0.70 (95% confidence interval (CI) -0.80, -0.54) points from T1 to T3. Predictors of distress were time since diagnosis, age, prior or concurrent intake of antidepressants or sedative medicine, prior emotional status, children living at home, feelings regarding femininity and attractiveness, and hospital. CONCLUSIONS: More than two-thirds of women with breast cancer experienced moderate or severe distress. Mean distress decreased slightly during surgical continuity of care. However, for some women, distress remained unchanged or even worsened. These findings highlight the need to identify the individual women with distress and offer them adequate support and care. PMID- 27179892 TI - Health-related quality of life in teenagers with a parent with cancer. AB - PURPOSE: Health-related quality of life (HRQoL) in teenagers exposed to parental cancer has shown divergent results as an outcome measure. In this study we wanted to: 1) compare the HRQoL of teenagers exposed to parental cancer (CASES) with normative European HRQoL data (NORMs) measured close to parental diagnosis and treatment; 2) study changes in the HRQoL of CASES from baseline to follow-up; 3) explore sex differences in the HRQoL of CASES; and 4) explore eventual confounders of HRQoL of CASES at baseline. METHODS: Forty-five families with one parent diagnosed with primary invasive cancer were included, these families had 69 teenagers. At the follow-up, 26 families with 29 teenagers complied. Both parents and teenagers filled in electronic questionnaires over the Internet. HRQoL in teenagers was self-rated by the KIDSCREEN-27 at baseline and follow-up, and the responses were compared to a European normative sample (NORMs). RESULTS: 1) The teenagers scored significantly lower on the Physical well-being dimension compared to the NORMs at baseline, while no significant differences were observed concerning the four other HRQoL dimensions. 2) Some significant improvements were observed on HRQoL dimensions from baseline to follow-up. 3) CASES girls showed a trend towards lower HRQoL scores compared to boys. 4) Parental cancer-related characteristics and family function were not related to teenagers' HRQoL, but so were teenagers' self-esteem. CONCLUSIONS: At group level, living with a parent who receives curative treatment for a recently diagnosed cancer affects teenagers' HRQoL to certain extent. Self-esteem is a confounder to teenagers' HRQoL in our sample. PMID- 27179891 TI - Burnout and the provision of psychosocial care amongst Australian cancer nurses. AB - PURPOSE: To assess the prevalence of burnout amongst Australian cancer nurses as well as investigate the systemic and individual factors associated with burnout, including training and supervision for nurses in psychosocial care. Burnout amongst cancer nurses can have serious consequences for the individual nurse, the hospital and patients. Psychosocial care has been demonstrated in many studies to reduce distress in cancer patients; however, previous studies have suggested that providing psychosocial care can be stressful if nurses feel they lack appropriate training. Psychosocial skill training and supervision may be a way of improving job satisfaction and reducing burnout amongst nurses. METHOD: Two hundred and thirty cancer nurses were recruited between November 2010 and April 2011 and completed an online questionnaire. RESULTS: Burnout levels within this population were found to be below nursing norms. Adequacy of training and supervision, frequency of supervision and percentage of role spent managing psychosocial care were found to be associated with burnout. Workload, Control, Reward and Community were independent predictors of burnout, and nurses with a greater mismatch in these areas identified as having High levels of burnout. CONCLUSIONS: Strategies to reduce burnout include providing cancer nurses with a varied and sustainable workload, awarding financial and social recognition of efforts and encouraging nurses to develop a sense of control over their work. Providing regular training and supervision in psychosocial care that is perceived to be adequate may also assist in reducing burnout. PMID- 27179893 TI - Physical symptom burden of post-treatment head and neck cancer patients influences their characterization of food: Findings of a repertory grid study. AB - BACKGROUND AND AIM: Dietary advice for post treatment head and neck cancer (HNC) patients emphasizes food characteristics of nutritional value and texture, and not patients' characterization of food. The aim of this study was to determine patients' characterization of food. METHODS: Repertory grid interviews were conducted with 19 orally-fed HNC patients between 4 and 10 months post-treatment to characterize foods commonly eaten, avoided and eaten sometimes. Patients compared and rated 12 foods using their own descriptors. Data were analyzed by General Procrustes Analysis (GPA). Socio-demographic status, taste and smell alterations, appetite and food intake data were also collected. Patient physical symptom burden was defined by University of Washington-Quality of Life Physical Function domain scores and used to stratify patients with "less physical symptom burden" (n = 11, score >= 61.7) or "greater physical symptom burden" (n = 8, score < 61.7). RESULTS: All patients used descriptors of taste, ease of eating, convenience, texture, potential to worsen symptoms and liking to characterize foods. Overall, avoided foods were characterized as having dry texture, while foods commonly eaten were characterized by their ease of eating and low potential to worsen symptoms. Descriptors of nutrition and smell were significant only for patients with greater physical symptom burden. CONCLUSIONS: Physical symptom burden influenced the characterization of foods among post-treatment HNC patients. Nutrition counseling must consider patients' physical symptom burden and the subsequent characterization of food that drive food selection or avoidance to facilitate dietary advice for adequate, appropriate and enjoyable food intake. PMID- 27179894 TI - Preliminary evaluation of reliability and validity of head and neck external lymphedema and fibrosis assessment criteria. AB - PURPOSE: Measurement of head and neck external lymphedema and fibrosis (LEF) is challenging. To address this gap, we developed the Head and Neck External Lymphedema and Fibrosis (HN-LEF) Assessment Criteria. This article aimed to report preliminary data on reliability and validity of the HN-LEF Assessment Criteria. METHODS: Sixty head and neck cancer (HNC) patients who were >=3-month post cancer therapy were recruited. Study measures included 1) demographic/medical data; 2) LEF physical examination completed independently by two staff members for interrater reliability (intrarater reliability completed by one of them); and 3) grayscale ultrasound examination of the head and neck skin. Reliability estimates used percent agreement and Kappa statistic. Validity was assessed via Spearman correlations of physical examination findings with ultrasound measurements. RESULTS: Fifty-one out of 60 HNC patients completed both physical examination and ultrasound assessments. Interrater reliability: 91.0% agreement (Kappa = 0.81, p < 0.001) on the presence of types of LEF; 84.9% agreement regarding the grade of LEF (Kappa = 0.70, p < 0.001) across all anatomic sites. Intrarater reliability: 96.1% agreement for type of LEF; and 91.4% agreement for grade across all sites. Ultrasound examination demonstrates characteristics and patterns for different types of LEF (particularly in the cheek, submental, and neck regions). CONCLUSIONS: The study provided initial reliability and validity data for a clinician-reported tool evaluating external LEF in the HNC population. These preliminary findings demonstrate that the tool had good reliability. Associations with the ultrasound examination results demonstrate that the tool validly captures soft tissue changes at select sites. Further validation of the tool is warranted. PMID- 27179895 TI - A qualitative study of blood and marrow transplant patient experiences participating in art making and music listening. AB - PURPOSE: To explore patient experiences of engaging in art making or music listening while receiving treatment in a blood and marrow transplant clinic. METHOD: Researchers recruited 25 individuals receiving blood and marrow transplant (BMT) treatment, 12 men and 13 women aged 22 to 74, from a Midwestern outpatient BMT clinic. Participants engaged in a painting activity or listened to music on an iPad using an internet music application for one hour. Researchers interviewed participants after the one-hour activity to gain insight into participants' perceptions of the art making or music listening experience. Interviews were recorded, transcribed verbatim, and independently coded by members of the research team. Researchers met on several occasions to analyse codes and agree on emerging themes. RESULTS: Nine themes emerged from the data including, Engaging in Activity, Art and Music in Daily Life, Expression, Engaging with Equipment, Novelty, BMT Process, Activity Process, Social Support, and Living Situation. Participants enjoyed art making and music listening and found the activities beneficial during treatment. CONCLUSIONS: Participants benefited from art making and music listening because these activities increased the variety of options available during treatment, allowed for self-expression, and could be done alone or with caregivers. PMID- 27179896 TI - The lived experiences of aboriginal adolescent survivors of childhood cancer during the recovering process in Taiwan: A descriptive qualitative research. AB - PURPOSE: The purpose of this study was to understand the experiences of Taiwanese aboriginal adolescent survivors of childhood cancer during the process of recovery. METHOD: A snowball sampling strategy was used to recruit participants from the pediatrics unit of a medical center in the eastern region of Taiwan. In depth interviews were conducted with 11 aboriginal adolescent childhood cancer survivors. The data were analyzed using content analysis. RESULTS: The results revealed three major themes with subthemes within each theme. The three major themes are: roots of resilience, transformation and growth, and meaning of traditional rituals for resilience. The three subthemes within "roots of resilience" include: "feeling secure through company of family, care and financial support", "receiving support from the important others and religion" and "learning to self-adjust". The three subthemes revealed within "transformation and growth" are: restructuring the relationship with peers, "appreciating parents' hard work", and "learning to seize the moment". The two subthemes within "meaning of traditional rituals to resilience" include: "feeling blessed with the power of ancestral spirits" and "strengthening ethnic identity". CONCLUSION: This study provided insight into the experiences of aboriginal adolescents as they recovered from childhood cancer. The experiences made positive impacts by inspiring growth in maturity and consolidating aboriginal ethnic identity. The adolescents were empowered by support from family, friends and clansmen, and by their participation in aboriginal rituals. As healthcare professionals care for the aboriginal adolescents, it is critical to consider this culturally and ethnically specific knowledge/experience of surviving cancer to improve quality of care. PMID- 27179897 TI - Not feeling sick from breast cancer: A framework on health status perceptions transition process. AB - PURPOSE: In what state of health do women with breast cancer consider themselves to be? Health professionals classify them as cancer victims but few studies have examined women's perceptions of their own health following a breast cancer diagnosis. We looked at the transition in health status perceptions between before and after receiving the diagnosis. METHODS: A grounded theory design was chosen to develop a framework. RESULTS: From an analysis of semi-structured individual interviews with 32 women, it emerged that 1) over a two-year period, the participants went through four iterative steps between receipt of the official diagnosis and the return of the level of energy once the treatments are done. Theses four steps are: reacting emotionally, facing the situation, constructing a new identity and reacting to social representations of cancer, 2) the participants did not feel sick from breast cancer. CONCLUSION: This study shows learning to live with a sword of Damocles over the head during the transition process. The emergent steps of the health status perceptions transition process in breast cancer trajectory give direction for care. PMID- 27179898 TI - Managing socio-institutional enclosure: A grounded theory of caregivers' attentiveness in hospital care. AB - PURPOSE: Caregivers' attentiveness is vital for healthcare quality, yet existing research lacks a specific definition and neglects its different forms and aspects. METHODS: This paper presents a qualitative, grounded theory of attentiveness in hospital oncology care. RESULTS: Our data show nine types of attentiveness. We answer the question why a caregiver practices one type of attentiveness in a certain situation, and not another type. First, it appears to be of crucial importance whether attentiveness is essential for giving care in the opinion of the caregiver. Second, the focus of attention is essential. Care given by doctors and nurses is always ambivalent; on the one hand, it concerns the body, and on the other hand, it involves the person whom that body belongs to. What is the caregiver (mainly) focused on? The significance of socio institutional enclosure emerged as a key theme within the findings. CONCLUSIONS: Socio-institutional enclosure concerns the space a caregiver may or may not experience to break free from the preponderant institutional orientation towards the physical body of the patient. At the intersection of the influence of socio institutional enclosure and the substance of the caregivers' concepts of care, three cultures are found that comprise the different types of attentiveness. PMID- 27179899 TI - C667T and A1298C polymorphisms of methylenetetrahydrofolate reductase gene and susceptibility to myocardial infarction: A systematic review and meta-analysis. AB - MTHFR C677T and A1298C polymorphisms have been reported to be associated with the risk of myocardial infarction (MI), although the results of previous studies have been inconsistent. The aim of this study was to explore whether these polymorphisms play a role in the genetic susceptibility to MI. A comprehensive search of MEDLINE and EMBASE databases was conducted for studies evaluating the association between the C667T and A1298C polymorphisms and MI risk. Odds ratios (OR) with 95% confidence intervals (CIs) were calculated to assess the strength of association in the dominant model, recessive model, allelic model, and genotypes contrast. A total of 47 studies were finally included in this meta analysis. Overall, the results showed no statistically significant association between C667T and A1298C polymorphisms and MI risk. However, in subgroup analysis by ethnicity, the T allele of C677T polymorphism was associated with a 63% increased risk of MI compared with the C allele (T vs. C, OR=1. 63, 95%CI=1.15 2.10, fixed effects) in African populations, while compared to wild homozygote genotype, CT genotype was associated with a decreased risk of MI in North American populations (CT vs. CC, OR=0.81, 95%CI=0.64-0.98, fixed effects). Moreover, C677T polymorphism had a protective effect against MI risk under the dominant model (OR=0.93, 945%CI=0.87-0.99, fixed effects) in elderly (>=50) population. The A1298C polymorphism was not significantly associated with MI risk. Unlike A1298C polymorphism, C677T polymorphism was associated with risk of MI in African, North American, and elderly populations. PMID- 27179900 TI - A systematic review and meta-regression of temporal trends in the excess mortality associated with diabetes mellitus after myocardial infarction. AB - BACKGROUND/OBJECTIVES: It is not well known whether the gap in outcomes after myocardial infarction (MI) between patients with and without diabetes mellitus (DM) has changed over time. We performed a systematic review and metaregression of temporal trends in the excess mortality associated with DM after MI. METHODS: We searched the PubMed database for studies reporting mortality data according to diabetic status in patients hospitalized for MI or acute coronary syndromes (ACS). We included 139 studies/cohorts for analysis (432,066 diabetic patients and 1,182,108 nondiabetic patients). RESULTS: When compared to their non-diabetic counterparts, patients with DM had an odds ratio (OR) [95% CI] of 1.66 [1.59 1.74] (P<0.0001) for early mortality, and of 1.86 [1.75-1.97] (P<0.0001) for 6 12months mortality. When all data from the 116 studies reporting early mortality were pooled, there was no significant relationship between calendar year and Log (OR). Likewise, when considering the 61 studies reporting 6-12months mortality, there was no significant relationship between calendar year and Log (OR). Similar to the overall pooled analysis, no significant relationship between inclusion year and Log (OR) for mortality in diabetic patients was observed in sensitivity analyses performed in studies with ST-elevation MI as inclusion criteria, in randomized trials, in studies including >2000 patients, and in studies with DM prevalence >20%. CONCLUSIONS: We found no evidence for temporal changes in the incremental mortality risk associated with DM in the setting of MI. The improvements in management of MI patients during the last decades have not been associated with a reduction of the gap between diabetic and non-diabetic patients. PMID- 27179901 TI - Association between retinal vein occlusion and risk of heart failure: A 12-year nationwide cohort study. AB - BACKGROUNDS: Retinal vein occlusion (RVO) is one of the major causes of visual impairment in elderly people. Risk factors for RVO are also common risk factors for cardiovascular disease, including heart failure (HF). However, the association between RVO and HF has not been evaluated. METHODS AND RESULTS: A retrospective propensity-score matched cohort study was conducted using national representative 1 million samples from the Korea National Health Insurance Service. The RVO group included patients with a first diagnosis of either central or branch RVO (n=1754) and the comparison group included randomly selected patients (n=8749) who were matched to sociodemographic factors and the year of RVO diagnosis. In the longitudinal cohort, HF developed in 11.6% and 8.0% of patients in the RVO and comparison groups, respectively, (p<0.001) during the 11 year follow-up period (median, 7.6years). RVO was significantly associated with an increased risk of HF after multivariable adjustment (HR=1.36; 95% CI, 1.16 1.60). In terms of HF subtypes, RVO was associated with the risk of ischemic HF but not with the risk of non-ischemic HF. The effect size (~HR) for HF by RVO was larger in patients without each comorbidity than in patients with each comorbidity. CONCLUSIONS: Our observational study on nationwide data suggests that RVO is associated with an increased risk of the incidence of HF, especially ischemic HF. An optimal surveillance strategy and referring from ophthalmologists to cardiologists should be considered in the presence of one or more additional HF risk factors in patients with RVO. PMID- 27179902 TI - ACE-inhibitors versus angiotensin receptor blockers for prevention of events in cardiovascular patients without heart failure - A network meta-analysis. AB - BACKGROUND: Angiotensin receptor blockers (ARBs) are a valuable option to reduce cardiovascular (CV) mortality and morbidity in cardiac patients in whom ACE inhibitors (ACE-Is) cannot be used. However, clinical outcome data from direct comparisons between ACE-Is and ARBs are scarce, and some data have recently suggested superiority of ACE-Is over ARBs. METHODS: We performed a Bayesian network-meta-analysis, with data from both direct and indirect comparisons, from 27 randomized controlled trials (RCTs), including a total population of 125,330 patients, to assess the effects of ACE-Is and ARBs on the composite endpoint of CV death, myocardial infarction (MI) and stroke, and on all-cause death, new onset heart failure (HF) and new-onset diabetes mellitus (DM) in high CV risk patients without HF. RESULTS: Using placebo as a common comparator, we found no significant differences between ACE-Is and ARBs in preventing the composite endpoint of CV death, MI and stroke (RR: 0.92; 95% CI 0.78-1.08). When components of the composite outcome were analysed separately, ACEi and ARBs were associated with a similar risk of CV death (RR: 0.92; 95% CI 0.73-1.10), MI (RR: 0.91; 95% CI 0.78-1.07) and stroke (RR: 0.97; 95% CI 0.79-1.19), as well as a similar incident risk of all-cause death (RR: 0.94; 95% CI 0.85-1.05), new-onset HF (RR: 0.92; 95% CI 0.77-1.15) and new-onset DM (RR: 99; 95% CI 0.81-1.21). CONCLUSIONS: With the limitations of indirect comparisons, we found that in patients at high CV risk without HF, ARBs were similar to ACE-Is in preventing the composite endpoint of CV death, MI and stroke. Compared with ARBs, we found no evidence of statistical superiority for ACE-Is, as a class, in preventing incident risk of all-cause death, CV death, MI, stroke, new-onset DM and new-onset HF. PMID- 27179903 TI - Cardiovascular magnetic resonance in rheumatology: Current status and recommendations for use. AB - Targeted therapies in connective tissue diseases (CTDs) have led to improvements of disease-associated outcomes, but life expectancy remains lower compared to general population due to emerging co-morbidities, particularly due to excess cardiovascular risk. Cardiovascular magnetic resonance (CMR) is a noninvasive imaging technique which can provide detailed information about multiple cardiovascular pathologies without using ionizing radiation. CMR is considered the reference standard for quantitative evaluation of left and right ventricular volumes, mass and function, cardiac tissue characterization and assessment of thoracic vessels; it may also be used for the quantitative assessment of myocardial blood flow with high spatial resolution and for the evaluation of the proximal coronary arteries. These applications are of particular interest in CTDs, because of the potential of serious and variable involvement of the cardiovascular system during their course. The International Consensus Group on CMR in Rheumatology was formed in January 2012 aiming to achieve consensus among CMR and rheumatology experts in developing initial recommendations on the current state-of-the-art use of CMR in CTDs. The present report outlines the recommendations of the participating CMR and rheumatology experts with regards to: (a) indications for use of CMR in rheumatoid arthritis, the spondyloarthropathies, systemic lupus erythematosus, vasculitis of small, medium and large vessels, myositis, sarcoidosis (SRC), and scleroderma (SSc); (b) CMR protocols, terminology for reporting CMR and diagnostic CMR criteria for assessment and quantification of cardiovascular involvement in CTDs; and (c) a research agenda for the further development of this evolving field. PMID- 27179904 TI - Resting multilayer 2D speckle-tracking TTE for detection of ischemic segments confirmed by invasive FFR part-2, using post-systolic-strain-index and time from aortic-valve-closure to regional peak longitudinal-strain. AB - PURPOSE: This study evaluated the post-systolic strain index (PSI), and the time interval between aortic valve closure (AVC) and regional peak longitudinal strain (PLS), measured by transthoracic echocardiography (TTE), for detection of left ventricular (LV) myocardial ischemic segments confirmed by invasive fractional flow reserve (FFR). MATERIALS AND METHODS: 39 stable patients (32 males; 65.8+/ 11.9years) with 46 coronary arteries at >=50% stenosis on invasive coronary angiography underwent 2D speckle tracking TTE (Vivid E9, GE Healthcare) and invasive FFR measurements. PSI, AVC and regional PLS in each LV segment were calculated. RESULTS: FFR <=0.80 was detected in 27 LV segments. There were no significant differences between segments supplied by FFR <=0.80 and FFR >0.80 vessels in either PSI or the time interval between AVC and regional PLS. To identify LV segments+/-FFR <=0.80, the receiver operator characteristic (ROC) curves for PSI, and the time interval between AVC and regional PLS had areas under the curve (AUC) values of 0.58 and 0.57, respectively, with best cut-off points of 12% (sensitivity 70.4%, specificity 57.9%) and 88ms (sensitivity 70.4%, specificity 52.6%), respectively, but the AUCs were not statistically significant. CONCLUSION: In stable coronary artery disease patients with >=50% coronary artery stenosis, measurement of PSI, and the time interval between AVC and regional PLS, on resting TTE, enabled the identification of LV segments with FFR <=0.80 using each appropriate threshold for PSI, and the time interval between AVC and regional PLS, with reasonable diagnostic accuracy. However, the AUC values were not statistically significant. PMID- 27179905 TI - Distribution of cuticular proteins in different structures of adult Anopheles gambiae. AB - Anopheles gambiae devotes over 2% (295) of its protein coding genes to structural cuticular proteins (CPs) that have been classified into 13 different families plus ten low complexity proteins not assigned to families. Small groups of genes code for identical proteins reducing the total number of unique cuticular proteins to 282. Is the large number because different structures utilize different CPs, or are all of the genes widely expressed? We used LC-MS/MS to learn how many products of these genes were found in five adult structures: Johnston's organs, the remainder of the male antennae, eye lenses, legs, and wings. Data were analyzed against both the entire proteome and a smaller database of just CPs. We recovered unique peptides for 97 CPs and shared peptides for another 35. Members of 11 of the 13 families were recovered as well as some unclassified. Only 11 CPs were present exclusively in only one structure while 43 CPs were recovered from all five structures. A quantitative analysis, using normalized spectral counts, revealed that only a few CPs were abundant in each structure. When the MS/MS data were run against the entire proteome, the majority of the top hits were to CPs, but peptides were recovered from an additional 467 proteins. CP peptides were frequently recovered from chitin-binding domains, confirming that protein-chitin interactions are not mediated by covalent bonds. Comparison with three other MS/MS analyses of cuticles or cuticle-rich structures augmented the current analysis. Our findings provide new insights into the composition of different mosquito structures and reveal the complexity of selection and utilization of genes coding for structural cuticular proteins. PMID- 27179906 TI - Use of [(18)F]Fluoro-2-deoxy-d-glucose Positron Emission Tomographic Imaging in the National Lung Screening Trial. AB - BACKGROUND: Positron emission tomography (PET) is a diagnostic tool for lung cancer evaluation. No studies have ascertained practice patterns and determined the appropriateness of PET imaging in a large group of US patients with screen detected lung nodules. METHODS: We analyzed participants in the National Lung Screening Trial (NLST) with positive screening test results and identified individuals with a PET scan performed prior to lung cancer diagnosis (diagnostic PET). Appropriate scan was defined as one performed in a patient with a nodule >= 0.8 cm. Logistic regression was used to assess factors associated with diagnostic PET scan use and appropriateness of PET scan use. RESULTS: Diagnostic PET imaging was performed in 1,556 of 14,195 patients (11%) with positive screen results; 331 of these (21%) were inappropriate. PET scan use by endemic fungal disease area was comparable although patients from the Northeast/Southeast were twice as likely as the West to have a diagnostic PET. Trial arm, older age, sex, nodule size >= 0.8 cm, upper lobe location, and spiculated margin were variables positively associated with use. Trial arm, older age, and spiculated margin were positively associated with appropriate use. Only 561 diagnostic PETs (36%) were recommended by a radiologist and 284 PETs performed for nodules < 0.8 cm (86%) were ordered despite no recommendation from a radiologist. CONCLUSIONS: PET imaging was differentially used in the NLST and inappropriately used in many cases against radiologist recommendations. These data suggest PET imaging may be overused in the lung cancer screening population and may contribute to excess health-care costs. PMID- 27179907 TI - Association Between Testosterone Replacement Therapy and the Incidence of DVT and Pulmonary Embolism: A Retrospective Cohort Study of the Veterans Administration Database. AB - BACKGROUND: Testosterone replacement therapy (TRT) prescriptions have increased several-fold in the last decade. There have been concerns regarding a possible increased incidence of DVT and pulmonary embolism (PE) with TRT. Few data support the association between TRT and DVT/PE. We evaluated the incidence of DVT and PE in men who were prescribed TRT for low serum total testosterone (sTT) levels. METHODS: This is a retrospective cohort study, conducted using data obtained from the Veterans Affairs Informatics and Computing Infrastructure. We compared the incidence of DVT/PE between those who received TRT and subsequently had normal on treatment sTT levels (Gp1), those who received TRT but continued to have low on treatment sTT (Gp2), and those who did not receive TRT (Gp3). Those with prior history of DVT/PE, cancer, hypercoagulable state, and chronic anticoagulation were excluded. RESULTS: The final cohort consisted of 71,407 subjects with low baseline sTT. Of these, 10,854 did not receive TRT (Gp3) and 60,553 received TRT. Of those who received TRT, 38,362 achieved normal sTT (Gp1) while 22,191 continued to have low sTT (Gp2). The incidence of DVT/PE was 0.5%, 0.4%, and 0.4% in Gp1, Gp2, and Gp3, respectively. Univariate, multivariate, and stabilized inverse probability of treatment weights analyses showed no statistically significant difference in DVT/PE-free survival between the various groups. CONCLUSIONS: This study did not detect a significant association between testosterone replacement therapy and risk of DVT/PE in adult men with low sTT who were at low to moderate baseline risk of DVT/PE. PMID- 27179908 TI - MicroRNA let-7d is a target of cannabinoid CB1 receptor and controls cannabinoid signaling. AB - Cannabinoid CB1 receptor, the molecular target of endocannabinoids and cannabis active components, is one of the most abundant metabotropic receptors in the brain. Cannabis is widely used for both recreational and medicinal purposes. Despite the ever-growing fundamental roles of microRNAs in the brain, the possible molecular connections between the CB1 receptor and microRNAs are surprisingly unknown. Here, by using reporter gene constructs that express interaction sequences for microRNAs in human SH-SY5Y neuroblastoma cells, we show that CB1 receptor activation enhances the expression of several microRNAs, including let-7d. This was confirmed by measuring hsa-let-7d expression levels. Accordingly, knocking-down CB1 receptor in zebrafish reduced dre-let-7d levels, and knocking-out CB1 receptor in mice decreased mmu-let-7d levels in the cortex, striatum and hippocampus. Conversely, knocking-down let-7d increased CB1 receptor mRNA expression in zebrafish, SH-SY5Y cells and primary striatal neurons. Likewise, in primary striatal neurons chronically exposed to a cannabinoid or opioid agonist, a let-7d-inhibiting sequence facilitated not only cannabinoid or opioid signaling but also cannabinoid/opioid cross-signaling. Taken together, these findings provide the first evidence for a bidirectional link between the CB1 receptor and a microRNA, namely let-7d, and thus unveil a new player in the complex process of cannabinoid action. PMID- 27179909 TI - Impact of CYP2E1, GSTA1 and GSTP1 gene variants on serum alpha glutathione S transferase level in patients undergoing anaesthesia. AB - BACKGROUND: The serum glutathione S-transferase alpha (alpha-GST) concentration has been used as a marker of hepatic condition. After sevoflurane anaesthesia a mild impairment of hepatocellular integrity was observed. Genetic polymorphisms in CYP2E1, GSTA1 and GSTP1 genes, affecting enzymes activity, may possibly influence the hepatotoxic effect of sevoflurane. The aim of this study was to assess the influence of genetic polymorphism of CYP2E1, GSTA1 and GSTP1 genes on serum alpha-GST level in 86 unrelated patients representing ASA physical status I II, undergoing laryngological surgery under general anaesthesia with sevoflurane. METHODS: The serum samples from three perioperative time points were analyzed using ELISA. Genetic variants were detected by pyrosequencing and sequencing. Finally, the statistical associations between serum alpha-GST concentration and analyzed alleles of CYP2E1, GSTP1 and GSTA1 genes were estimated. RESULTS: The allele GSTA1*B (-567G, -69T, -52A) frequency was 0.43, whereas the alleles c.313G and c.341T of GSTP1 were identified with frequencies of 0.28 and 0.1 respectively. The -1053T allele of the CYP2E1 gene was observed with 0.01 frequency. We found serum alpha-GST concentrations in homozygous changes c.313A>G and c.341C>T of the GSTP1 gene significantly higher at the end of anaesthesia as compared with the levels at pre-anaesthetic and 24 h post-anaesthetic time points. Moreover, GSTA1 wild type genotype was associated with increased alpha GST concentration at 24 h after the end of anaesthesia. CONCLUSIONS: GSTP1 gene polymorphism has an impact on the perioperative serum alpha-GST concentration in patients undergoing sevoflurane anaesthesia. A similar association, although not statistically significant exists between GSTA1 gene variants and perioperative serum alpha-GST level. PMID- 27179910 TI - A 20-year perspective of in hospital cardiac arrest: Experiences from a university hospital with focus on wards with and without monitoring facilities. AB - BACKGROUND: Knowledge about change in the characteristics and outcome of in hospital cardiac arrests (IHCAs) is insufficient. AIM: To describe a 20year perspective of in hospital cardiac arrest (IHCA) in wards with and without monitoring capabilities. SETTINGS: Sahlgrenska University Hospital (800 beds). The number of beds varied during the time of survey from 850-746 TIME: 1994-2013. METHODS: Retrospective registry study. Patients were assessed in four fiveyear intervals. INCLUSION CRITERIA: Witnessed and nonwitnessed IHCAs when cardiopulmonary resuscitation (CPR) was attempted. EXCLUSION CRITERIA: Age below 18years. RESULTS: In all, there were 2340 patients with IHCA during the time of the survey. 30-Day survival increased significantly in wards with monitoring facilities from 43.5% to 55.6% (p=0.002) for trend but not in wards without such facilities (p=0.003 for interaction between wards with/without monitoring facilities and time period). The CPC-score among survivors did not change significantly in any of the two types of wards. In wards with monitoring facilities there was a significant reduction of the delay time from collapse to start of CPR and an increase in the proportion of patients who were defibrillated before the arrival of the rescue team. In wards without such facilities there was a significant reduction of the delay from collapse to defibrillation. However, the latter observation corresponds to a marked decrease in the proportion of patients found in ventricular fibrillation. CONCLUSION: In a 20year perspective the treatment of in hospital cardiac arrest was characterised by a more rapid start of treatment. This was reflected in a significant increase in 30-day survival in wards with monitoring facilities. In wards without such facilities there was a decrease in patients found in ventricular fibrillation. PMID- 27179912 TI - Beta blockers and cancer prognosis - The role of immortal time bias: A systematic review and meta-analysis. AB - BACKGROUND: Findings from experimental and observational studies have suggested beneficial effects of beta blocker (BB) use on cancer survival. Nevertheless, results have been inconclusive and there have been concerns that the observed associations might have resulted from immortal time bias (ITB). We conducted a systematic review and meta-analysis to summarize existing evidence, paying particular attention to this potential source of bias. METHODS: A systematic literature search was performed in PubMed and Web of Science. Studies investigating the association between BB use and overall or cancer-specific survival were included. Summary estimates were derived from meta-analyses using random effects models. The potential influence of ITB was investigated. RESULTS: We identified 30 eligible studies including 88,026 cancer patients in total. We deemed 11 studies to be at high or unclear risk of ITB. Including all studies in the meta-analysis, BB users had a significantly better overall (hazard ratio (HR) 0.88, 95% CI 0.79-0.97) and cancer-specific (HR 0.75, 95% CI 0.64-0.88) survival. Excluding the studies deemed to be prone to ITB resulted in HRs (95% CIs) of 1.00 (0.93-1.07) and 0.90 (0.83-0.98), respectively. Analyses on cancer site and BB type did not show beneficial associations besides overall survival among melanoma patients. However, melanoma-specific survival was not improved. CONCLUSION: We found no clinically meaningful evidence for an association between BB use and survival after excluding studies with a possible ITB. Our results support suggestions that the proposed beneficial effect of BBs on cancer survival might be based on ITB. PMID- 27179911 TI - The "induced hyperactivity" test for the de-risking of potential off-target activity of antihypertensive drugs. AB - INTRODUCTION: Compound X is a new proprietary antihypertensive agent that induces its pharmacodynamic effect at an approximate plasma Cmax.u of 0.6nmol/L (rat hypertension model). However, Compound X also shows potent off-target activity at PDE-10a (IC50~12nmol/L). Since PDE-10a is expressed predominantly in brain (striatum) and inhibition/knockout of PDE-10a have been reported to result in anti-psychotic effects, we have established the "induced hyperactivity" test for CNS de-risking of Compound X. METHODS: Male Wistar rats treated orally with vehicle or Compound X (single dose; 1-3-10mg/kg) were assessed for exploratory locomotor activity following induction of hyperactivity by d-amphetamine (2mg/kg) or the NMDA antagonist MK-801 (0.2mg/kg). The assay was validated with anti psychotic drugs (haloperidol, clozapine). RESULTS: Induced hyperactivity was not antagonized by Compound X at doses relevant for its primary pharmacodynamic activity (0.1-0.3mg/kg, rat). Although sufficient plasma concentrations were reached with Compound X (Cmax.u up to ~8nmol/L at 10mg/kg) to show its PDE-10a activity, its low brain penetration (~10%) likely precluded any meaningful PDE 10a inhibition. In comparison, other blood pressure lowering agents such as prazosin (alpha-1 adrenoceptor antagonist) and isradipine (L-Type Ca(2+) channel blocker), but not the NO-donor ISDN, tended to attenuate induced hyperactivity in rats at high doses. CONCLUSION: The relevance of a potent in-vitro off-target hit (PDE-10a inhibition) by Compound X was attenuated by a robust in-vivo assay (rat induced hyperactivity test), hence lowering the potential liability profile of Compound X. Finally, this piece of investigative safety pharmacology work enabled early de-risking of Compound X based on its primary pharmacodynamic activity in a relevant rat model. PMID- 27179913 TI - A collaborative study to establish the 1st WHO International Standard for human cytomegalovirus for nucleic acid amplification technology. AB - Variability in the performance of nucleic acid amplification technology (NAT) based assays presents a significant problem in the diagnosis and management of human cytomegalovirus (HCMV) infections. Here we describe a collaborative study to evaluate the suitability of candidate reference materials to harmonize HCMV viral load measurements in a wide range of NAT assays. Candidate materials comprised lyophilized Merlin virus, liquid Merlin virus, liquid AD169 virus, and purified HCMV Merlin DNA cloned into a bacterial artificial chromosome. Variability in the laboratory mean HCMV concentrations determined for virus samples across the different assays was 2 log10. Variability for the purified DNA sample was higher (>3 log10). The agreement between laboratories was markedly improved when the potencies of the liquid virus samples were expressed relative to the lyophilized virus candidate. In contrast, the agreement between laboratories for the purified DNA sample was not improved. Results indicated the suitability of the lyophilized Merlin virus preparation as the 1st WHO International Standard for HCMV for NAT. It was established in October 2010, with an assigned potency of 5 * 10(6) International Units (IU) (NIBSC code 09/162). It is intended to be used to calibrate secondary references, used in HCMV NAT assays, in IU. PMID- 27179914 TI - Predictors of processing-based task performance in bilingual and monolingual children. AB - In the present study we examined performance of bilingual Spanish-English speaking and monolingual English-speaking school-age children on a range of processing-based measures within the framework of Baddeley's working memory model. The processing-based measures included measures of short-term memory, measures of working memory, and a novel word-learning task. Results revealed that monolinguals outperformed bilinguals on the short-term memory tasks but not the working memory and novel word-learning tasks. Further, children's vocabulary skills and socioeconomic status (SES) were more predictive of processing-based task performance in the bilingual group than the monolingual group. Together, these findings indicate that processing-based tasks that engage verbal working memory rather than short-term memory may be better-suited for diagnostic purposes with bilingual children. However, even verbal working memory measures are sensitive to bilingual children's language-specific knowledge and demographic characteristics, and therefore may have limited clinical utility. PMID- 27179915 TI - Effective vaccine communication during the disneyland measles outbreak. AB - Vaccine refusal rates have increased in recent years, highlighting the need for effective risk communication, especially over social media. Fuzzy-trace theory predicts that individuals encode bottom-line meaning ("gist") and statistical information ("verbatim") in parallel and those articles expressing a clear gist will be most compelling. We coded news articles (n=4581) collected during the 2014-2015 Disneyland measles for content including statistics, stories, or bottom line gists regarding vaccines and vaccine-preventable illnesses. We measured the extent to which articles were compelling by how frequently they were shared on Facebook. The most widely shared articles expressed bottom-line gists, although articles containing statistics were also more likely to be shared than articles lacking statistics. Stories had limited impact on Facebook shares. Results support Fuzzy Trace Theory's predictions regarding the distinct yet parallel impact of categorical gist and statistical verbatim information on public health communication. PMID- 27179916 TI - Dorsal and ventral language pathways in persistent developmental stuttering. AB - Persistent developmental stuttering is a speech disorder that affects an individual's ability to fluently produce speech. While the disorder mainly manifests in situations that require language production, it is still unclear whether persistent developmental stuttering is indeed a language impairment, and if so, which language stream is implicated in people who stutter. In this study, we take a neuroanatomical approach to this question by examining the structural properties of the dorsal and ventral language pathways in adults who stutter (AWS) and fluent controls. We use diffusion magnetic resonance imaging and individualized tract identification to extract white matter volumes and diffusion properties of these tracts in samples of adults who do and do not stutter. We further quantify diffusion properties at multiple points along the tract and examine group differences within these diffusivity profiles. Our results show differences in the dorsal, but not in the ventral, language-related tracts. Specifically, AWS show reduced volume of the left dorsal stream, as well as lower anisotropy in the right dorsal stream. These data provide neuroanatomical support for the view that stuttering involves an impairment in the bidirectional mapping between auditory and articulatory cortices supported by the dorsal pathways, not in lexical access and semantic aspects of language processing which are thought to rely more heavily on the left ventral pathways. PMID- 27179917 TI - A general magnitude system in human adults: Evidence from a subliminal priming paradigm. AB - Despite general agreement that number and other magnitudes share analog format, there is disagreement about the extent to which representations of numerical and non-numerical magnitude recruit common cognitive and neural resources. Cross dimensional interactions between number and other magnitudes on Stroop-like tasks have been taken as evidence for integration across magnitudes, but such effects are subject to alternative interpretations that allow for differentiated representations. Here we use a subliminal priming paradigm to test for interactions between different magnitudes (number and area) when one magnitude is not consciously detectable. Across two experiments, we first provide evidence for the feasibility of this paradigm by demonstrating that transfer occurs within the dimension of number; that is, symbolic numerals (Arabic digits) that were subliminally primed affected judgments of non-symbolic numerosities in target displays. Crucially, we also found transfer across magnitudes-from subliminally primed numerals to target displays of cumulative surface area whether participants made an ordinal judgment (i.e., "which array is larger in area?") or judged whether two arrays were the same or different in area. These findings suggest that representations of number and area are not fully differentiated. Moreover, they provide unique support for a general magnitude system that includes direct connections, or overlap, between the neural codes for numerical and non-numerical magnitudes. PMID- 27179918 TI - The Power of Inbreeding: NGS-Based GWAS of Rice Reveals Convergent Evolution during Rice Domestication. AB - Low-coverage whole-genome sequencing is an effective strategy for genome-wide association studies in humans, due to the availability of large reference panels for genotype imputation. However, it is unclear whether this strategy can be utilized in other species without reference panels. Using simulations, we show that this approach is even more relevant in inbred species such as rice (Oryza sativa L.), which are effectively haploid, allowing easy haplotype construction and imputation-based genotype calling, even without the availability of large reference panels. We sequenced 203 rice varieties with well-characterized phenotypes from the United States Department of Agriculture Rice Mini-Core Collection at an average depth of 1.5* and used the data for mapping three traits. For the first two traits, amylose content and seed length, our approach leads to direct identification of the previously identified causal SNPs in the major-effect loci. For the third trait, pericarp color, an important trait underwent selection during domestication, we identified a new major-effect locus. Although known loci can explain color variation in the varieties of two main subspecies of Asian domesticated rice, japonica and indica, the new locus identified is unique to another domesticated rice subgroup, aus, and together with existing loci, can fully explain the major variation in pericarp color in aus. Our discovery of a unique genetic basis of white pericarp in aus provides an example of convergent evolution during rice domestication and suggests that aus may have a domestication history independent of japonica and indica. PMID- 27179919 TI - Functional Partition of Cpn60alpha and Cpn60beta Subunits in Substrate Recognition and Cooperation with Co-chaperonins. PMID- 27179920 TI - Role of UDP-Glucuronic Acid Decarboxylase in Xylan Biosynthesis in Arabidopsis. AB - UDP-xylose (UDP-Xyl) is the Xyl donor used in the synthesis of major plant cell wall polysaccharides such as xylan (as a backbone-chain monosaccharide) and xyloglucan (as a branching monosaccharide). The biosynthesis of UDP-Xyl from UDP glucuronic acid (UDP-GlcA) is irreversibly catalyzed by UDP-glucuronic acid decarboxylase (UXS). Until now, little has been known about the physiological roles of UXS in plants. Here, we report that AtUXS1, AtUXS2, and AtUXS4 are located in the Golgi apparatus whereas AtUXS3, AtUXS5, and AtUXS6 are located in the cytosol. Although all six single AtUXS T-DNA mutants and the uxs1 usx2 uxs4 triple mutant show no obvious phenotype, the uxs3 uxs5 uxs6 triple mutant has an irregular xylem phenotype. Monosaccharide analysis showed that Xyl levels decreased in uxs3 uxs5 uxs6 and linkage analysis confirmed that the xylan content in uxs3 xus5 uxs6 declined, indicating that UDP-Xyl from cytosol AtUXS participates in xylan synthesis. Gel-permeation chromatography showed that the molecular weight of non-cellulosic polysaccharides in the triple mutants, mainly composed of xylans, is lower than that in the wild type, suggesting an effect on the elongation of the xylan backbone. Upon saccharification treatment stems of the uxs3 uxs5 uxs6 triple mutants released monosaccharides with a higher efficiency than those of the wild type. Taken together, our results indicate that the cytosol UXS plays a more important role than the Golgi-localized UXS in xylan biosynthesis. PMID- 27179921 TI - Motion management during SBRT for oligometastatic cancer: Results of a prospective phase II trial. AB - PURPOSE: To optimize the local control of stereotactic body radiotherapy (SBRT) using the Vero-SBRT system and respiratory motion management in patients with oligometastatic cancer. MATERIALS AND METHODS: Patients with five or less metastases were eligible. In metastases with significant motion, a fiducial was implanted for Vero dynamic tracking. For other metastases an internal target volume (ITV) was defined to encompass the respiratory tumor trajectory. A dose of 50Gy in 10 fractions was prescribed on the 80% isodose line. RESULTS: We treated 87 metastases in 44 patients, with colorectal cancer as the most common primary origin (65.9%). Metastatic sites were mainly lung (n=62) and liver (n=17). Twenty seven metastases were treated with dynamic tracking, the remaining 60 using the ITV-concept. Three patients (7%) experienced grade ?3 toxicity. After a median follow-up of 12months, the overall one-year local control (LC) amounted to 89% (95% CI 77-95%), with corresponding values of 90% and 88% for the metastases irradiated with the ITV-approach and dynamic tracking, respectively. Median progression-free survival reached 6.5months, one-year overall survival 95%. CONCLUSIONS: SBRT with proper respiratory motion management resulted in a high LC and an acceptable toxicity profile in oligometastatic cancer patients. PMID- 27179922 TI - Autism and cerebellar dysfunction: Evidence from animal models. AB - Autism is a prevalent neurodevelopmental disorder whose origins are not well understood. Cerebellar involvement has been implicated in the pathogenesis of autism spectrum disorders with increasing evidence from both clinical studies and animal models supporting an important role for cerebellar dysfunction in autism spectrum disorders. This article discusses the various cerebellar contributions to autism spectrum disorders. Both clinical and preclinical studies are discussed and future research directions highlighted. PMID- 27179925 TI - Safety and feasibility of red cell exchange for sickle cell disease across Canada. AB - We outline a case whereby RBCX was successfully provided over disparate geographical areas and time zones in Canada and overcame the logistical challenges of coordinating care across four different health care systems with the application of modern telecommunication technologies. We present this case as a model for other SCD providers and patients. PMID- 27179923 TI - Iron oxide nanoparticles for neuronal cell applications: uptake study and magnetic manipulations. AB - BACKGROUND: The ability to direct and manipulate neuronal cells has important potential in therapeutics and neural network studies. An emerging approach for remotely guiding cells is by incorporating magnetic nanoparticles (MNPs) into cells and transferring the cells into magnetic sensitive units. Recent developments offer exciting possibilities of magnetic manipulations of MNPs loaded cells by external magnetic fields. In the present study, we evaluated and characterized uptake properties for optimal loading of cells by MNPs. We examined the interactions between MNPs of different cores and coatings, with primary neurons and neuron-like cells. RESULTS: We found that uncoated-maghemite iron oxide nanoparticles maximally interact and penetrate into cells with no cytotoxic effect. We observed that the cellular uptake of the MNPs depends on the time of incubation and the concentration of nanoparticles in the medium. The morphology patterns of the neuronal cells were not affected by MNPs uptake and neurons remained electrically active. We theoretically modeled magnetic fluxes and demonstrated experimentally the response of MNP-loaded cells to the magnetic fields affecting cell motility. Furthermore, we successfully directed neurite growth orientation along regeneration. CONCLUSIONS: Applying mechanical forces via magnetic mediators is a useful approach for biomedical applications. We have examined several types of MNPs and studied the uptake behavior optimized for magnetic neuronal manipulations. PMID- 27179924 TI - Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy with lobaplatin and docetaxel to treat synchronous peritoneal carcinomatosis from gastric cancer: Results from a Chinese center. AB - BACKGROUND: This work was to evaluate the efficacy and safety of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) with lobaplatin and docetaxel to treat peritoneal carcinomatosis (PC) from gastric cancer (GC). METHODS: A total of 50 consecutive GC PC patients treated by 52 CRS+HIPEC procedures with lobaplatin 50 mg/m(2) and docetaxel 60 mg/m(2) in 6000 mL of normal saline at (43 +/- 0.5) degrees C for 60 min. The primary endpoint was overall survival (OS), and the secondary endpoints were perioperative safety profiles. RESULTS: At the median follow-up of 22.5 (range, 5.1-50.7) months, the median OS was 14.3 (95% CI 7.6-21.0) months, and the 1-, 2-, and 3-year survival rates were 58%, 40%, and 32%, respectively. Mortality and serious adverse event (grade 3-5) morbidity rates in postoperative 30 days were 0.0% and 23.1%, respectively. Univariate analysis identified 4 parameters with significant effects on OS: completeness of cytoreduction (CC) 0-1, normal (N) the preoperative tumor markers level (TM), adjuvant chemotherapy >=6 cycles, and peritoneal cancer index <=20. However, multivariate analysis identified CC0-1, perioperative TM (N), adjuvant chemotherapy >=6 cycles as the independent predictor for better survival. CONCLUSIONS: CRS+HIPEC with lobaplatin and docetaxel to treat selected GC PC could improve OS, with acceptable perioperative safety. PMID- 27179926 TI - Smart blood cell and microvesicle-based Trojan horse drug delivery: Merging expertise in blood transfusion and biomedical engineering in the field of nanomedicine. AB - Therapeutic and diagnostic applications of nanomedicine are playing increasingly important roles in human health. Various types of synthetic nanoparticles, including liposomes, micelles, and other nanotherapeutic platforms and conjugates, are being engineered to encapsulate or carry drugs for treating diseases such as cancer, cardiovascular disorders, neurodegeneration, and inflammations. Nanocarriers are designed to increase the half-life of drugs, decrease their toxicity and, ideally, target pathological sites. Developing smart carriers with the capacity to deliver drugs specifically to the microenvironment of diseased cells with minimum systemic toxicity is the goal. Blood cells, and potentially also the liposome-like micro- and nano-vesicles they generate, may be regarded as ideally suited to perform such specific targeting with minimum immunogenic risks. Blood cell membranes are "decorated" with complex physiological receptors capable of targeting and communicating with other cells and tissues and delivering their content to the surrounding pathological microenvironment. Blood cells, such as erythrocytes, have been developed as permeable carriers to release drugs to diseased tissues or act as biofactory allowing enzymatic degradation of a pathological substrate. Interestingly, attempts are also being made to improve the targeting capacity of synthetic nanoparticles by "decorating" their surface with blood cell membrane receptor like biochemical structures. Research is needed to further explore the benefits that blood cell-derived microvesicles, as a Trojan horse delivery systems, can bring to the arsenal of therapeutic micro- and nanotechnologies. This short review focuses on the therapeutic roles that red blood cells and platelets can play as smart drug-delivery systems, and highlights the benefits that blood transfusion expertise can bring to this exciting and novel biomedical engineering field. PMID- 27179927 TI - Recognition and treatment of syndromes linked to dysregulation of the alternative complement pathway. PMID- 27179928 TI - Improved tolerance to post-anthesis drought stress by pre-drought priming at vegetative stages in drought-tolerant and -sensitive wheat cultivars. AB - Wheat crop endures a considerable penalty of yield reduction to escape the drought events during post-anthesis period. Drought priming under a pre-drought stress can enhance the crop potential to tolerate the subsequent drought stress by triggering a faster and stronger defense mechanism. Towards these understandings, a set of controlled moderate drought stress at 55-60% field capacity (FC) was developed to prime the plants of two wheat cultivars namely Luhan-7 (drought tolerant) and Yangmai-16 (drought sensitive) during tillering (Feekes 2 stage) and jointing (Feekes 6 stage), respectively. The comparative response of primed and non-primed plants, cultivars and priming stages was evaluated by applying a subsequent severe drought stress at 7 days after anthesis. The results showed that primed plants of both cultivars showed higher potential to tolerate the post-anthesis drought stress through improved leaf water potential, more chlorophyll, and ribulose-1, 5-bisphosphate carboxylase/oxygenase contents, enhanced photosynthesis, better photoprotection and efficient enzymatic antioxidant system leading to less yield reductions. The primed plants of Luhan-7 showed higher capability to adapt the drought stress events than Yangmai-16. The positive effects of drought priming to sustain higher grain yield were pronounced in plants primed at tillering than those primed at jointing. In consequence, upregulated functioning of photosynthetic apparatus and efficient enzymatic antioxidant activities in primed plants indicated their superior potential to alleviate a subsequently occurring drought stress, which contributed to lower yield reductions than non-primed plants. However, genotypic and priming stages differences in response to drought stress also contributed to affect the capability of primed plants to tolerate the post-anthesis drought stress conditions in wheat. PMID- 27179929 TI - Zika crisis in Brazil: challenges in research and development. AB - Infection with the Zika virus (ZIKV) usually causes a mild acute illness, but two major severe syndromes have been described during the epidemic in Brazil: microcephaly and the Guillain-Barre Syndrome. There is now much evidence to show that ZIKV can infect and damage neuronal cells in vitro. In experimental animals, ZIKV has significant neurotropism and can cause brain damage. At present, diagnosis is still a challenge in the field and there is no treatment available. Another major challenge is that one must devise therapies for pregnant women, at all stages of pregnancy. Devising adequate treatment for ZIKV infections represents a challenge that will only be met by the joint effort of the research community. PMID- 27179930 TI - Phosphodiesterase 5/protein kinase G signal governs stemness of prostate cancer stem cells through Hippo pathway. AB - Cancer stem cells (CSC) are critical for initiation, metastasis, and relapse of cancers, however, the underlying mechanism governing stemness of CSC remains unknown. Herein, we have investigated the roles of phosphodiesterase 5 (PDE5) in stemness of prostate cancer cells. Both PDE5 and WW domain-containing transcription regulator protein-1 (TAZ), a core effector of Hippo pathway, are highly expressed in the PC3-derived cancer stem cells (PCSC). Either TAZ knockdown or inhibition of PDE5 activity attenuated colony formation, altered expression patterns of stem cell markers, and enhanced cisplatin cytotoxicity, resulting in attenuation of stemness in PCSC. In addition, inhibition of PDE5 activity by its specific inhibitors activates cGMP-dependent protein kinase G (PKG), which in turn induces MST/LATS kinases, resulting in cytosolic degradation of TAZ and activation of Hippo pathway. Accordingly, knockdown of TAZ almost completely abolished PDE5 inhibitor-induced attenuation in stemness in cultured PCSC, whereas knockdown of TAZ not only abolished PDE5 inhibitor-induced attenuation in stemness but also facilitated PDE5 inhibitor-induced trans differentiation in PCSC xenografts. Together, the present study has uncovered that PDE/cGMP/PKG signal targets to Hippo/TAZ pathway in maintaining stemness of PCSC, and suggested that PDE5 inhibitors in combination with chemotherapeutic agents could effectively prevent initiation, metastasis, and relapse of prostate cancer. PMID- 27179931 TI - A method for objectively quantifying propidium iodide exclusion in organotypic hippocampal slice cultures. AB - BACKGROUND: Organotypic hippocampal slice cultures (OHSCs) are an attractive in vitro model to examine mechanisms of neuronal injury, because the normal hippocampal architecture, function and cellular diversity are mostly preserved. The effects of exposure to excitotoxins such as N-methyl-d-aspartate (NMDA) on cell viability can be determined by propidium iodide (PI) staining. NEW METHOD: We describe a simple method to objectively quantify cell death in NMDA exposed slice cultures using PI that provides a standardized means of quantifying cell death in hippocampal subfields without the need to induce maximal cell death in each slice. The method employs separation of subfields using simple landmarks and densitometric quantification of PI intensity in 10 template-oriented counting fields. RESULTS: We show that exposure to increasing concentrations of NMDA results in a dose-dependent increase in PI uptake. Additionally, our method facilitates the comparison of cell death in different hippocampal subfields, such as dentate gyrus, CA1 and CA3. Our results show marked differences of PI uptake in the hippocampal regions with the CA1 area being most sensitive to NMDA-induced injury. COMPARISON WITH EXISTING METHOD(S): The method provides a standardized format for quantifying PI exclusion in OHSCs that can be applied to cultures of differing shapes and sizes, permits comparisons between hippocampal subfields and does not require induction of maximal cell death. CONCLUSION: The method of quantifying PI uptake described herein allows for an objective, quantitative and reproducible analysis and comparison of cell death in distinct regions of OHSCs. PMID- 27179932 TI - Should Physicians be Encouraged to use Generic Names and to Prescribe Generic Drugs? AB - While using the brand names seems like a trivial issue at the outset, using these names is inherently problematic. Cardiovascular drugs remain the most commonly prescribed drugs by the physicians. The junior doctors are likely to introject practices of their seniors and consequently to reciprocate from the experiences learnt from their preceptors. Using the generic names may be one way to facilitate prescription of the generic drugs who have a better cost profile and similar efficacy than the more expensive branded drugs. In this editorial, we have outlined several arguments to suggest the importance of using the generic names in academic discussions and clinical documentation. PMID- 27179933 TI - Strong synergy with APR-246 and DNA-damaging drugs in primary cancer cells from patients with TP53 mutant High-Grade Serous ovarian cancer. AB - BACKGROUND: Mutation in the tumor suppressor gene TP53 is an early event in the development of high-grade serous (HGS) ovarian cancer and is identified in more than 96 % of HGS cancer patients. APR-246 (PRIMA-1(MET)) is the first clinical stage compound that reactivates mutant p53 protein by refolding it to wild type conformation, thus inducing apoptosis. APR-246 has been tested as monotherapy in a Phase I/IIa clinical study in hematological malignancies and prostate cancer with promising results, and a Phase Ib/II study in combination with platinum based therapy in ovarian cancer is ongoing. In the present study, we investigated the anticancer effects of APR-246 in combination with conventional chemotherapy in primary cancer cells isolated from ascitic fluid from 10 ovarian, fallopian tube, or peritoneal cancer patients, 8 of which had HGS cancer. METHODS: Cell viability was assessed with fluorometric microculture cytotoxicity assay (FMCA) and Combination Index was calculated using the Additive model. p53 status was determined by Sanger sequencing and single strand conformation analysis, and p53 protein expression by western blotting. RESULTS: We observed strong synergy with APR-246 and cisplatin in all tumor samples carrying a TP53 missense mutation, while synergistic or additive effects were found in cells with wild type or TP53 nonsense mutations. Strong synergy was also observed with carboplatin or doxorubicin. Moreover, APR-246 sensitized TP53 mutant primary ovarian cancer cells, isolated from a clinically platinum-resistant patient, to cisplatin; the IC50 value of cisplatin decreased 3.6 fold from 6.5 to 1.8 MUM in the presence of clinically relevant concentration of APR-246. CONCLUSION: These results suggest that combination treatment with APR-246 and DNA-damaging drugs could significantly improve the treatment of patients with TP53 mutant HGS cancer, and thus provide strong support for the ongoing clinical study with APR-246 in combination with carboplatin and pegylated liposomal doxorubicin in patients with recurrent HGS cancer. PMID- 27179934 TI - Bioaccumulation and elimination of mercury in juvenile seabass (Dicentrarchus labrax) in a warmer environment. AB - Warming is an expected impact of climate change that will affect coastal areas in the future. These areas are also subjected to strong anthropogenic pressures leading to chemical contamination. Yet, the consequences of both factors for marine ecosystems, biota and consumers are still unknown. The present work aims to investigate, for the first time, the effect of temperature increase on bioaccumulation and elimination of mercury [(total mercury (THg) and methylmercury (MeHg)] in three tissues (muscle, liver, and brain) of a commercially important seafood species - European seabass (Dicentrarchus labrax). Fish were exposed to the ambient temperature currently used in seabass rearing (18 degrees C) and to the expected ocean warming (+4 degrees C, i.e. 22 degrees C), as well as dietary MeHg during 28 days, followed by a depuration period of 28 days fed with a control diet. In both temperature exposures, higher MeHg contents were observed in the brain, followed by the muscle and liver. Liver registered the highest elimination percentages (EF; up to 64% in the liver, 20% in the brain, and 3% in the muscle). Overall, the results clearly indicate that a warming environment promotes MeHg bioaccumulation in all tissues (e.g. highest levels in brain: 8.1mgkg(-1) ww at 22 degrees C against 6.2mgkg(-1) ww at 18 degrees C after 28 days of MeHg exposure) and hampers MeHg elimination (e.g. liver EF decreases after 28 days of depuration: from 64.2% at 18 degrees C to 50.3% at 22 degrees C). These findings suggest that seafood safety may be compromised in a warming context, particularly for seafood species with contaminant concentrations close to the current regulatory levels. Hence, results point out the need to strengthen research in this area and to revise and/or adapt the current recommendations regarding human exposure to chemical contaminants through seafood consumption, in order to integrate the expected effects of climate change. PMID- 27179935 TI - Monitoring the effect of air pollution episodes on health care consultations and ambulance call-outs in England during March/April 2014: A retrospective observational analysis. AB - There is an increasing body of evidence illustrating the negative health effects of air pollution including increased risk of respiratory, cardiac and other morbid conditions. During March and April 2014 there were two air pollution episodes in England that occurred in close succession. We used national real-time syndromic surveillance systems, including general practitioner (GP) consultations, emergency department attendances, telehealth calls and ambulance dispatch calls to further understand the impact of these short term acute air pollution periods on the health seeking behaviour of the general public. Each air pollution period was comparable with respect to particulate matter concentrations (PM10 and PM2.5), however, the second period was longer in duration (6 days vs 3 days) and meteorologically driven 'Sahara dust' contributed to the pollution. Health surveillance data revealed a greater impact during the second period, with GP consultations, emergency department attendances and telehealth (NHS 111) calls increasing for asthma, wheeze and difficulty breathing indicators, particularly in patients aged 15-64 years. Across regions of England there was good agreement between air quality levels and health care seeking behaviour. The results further demonstrate the acute impact of short term air pollution episodes on public health and also illustrate the potential role of mass media reporting in escalating health care seeking behaviour. PMID- 27179936 TI - Dietary intake of working women with children does not appear to be influenced by hours of employment: A secondary analysis of the Australian Health Survey (2011 2013). AB - Women with children often fulfil multiple roles of running a household, raising a family and working outside the home. Good nutrition during this time is important to optimise their performance and prevent lifestyle diseases. Women also act as nutritional gatekeepers for their family. The dual burden of paid employment and unpaid family work may be associated with time scarcity in mothers which can impact food preparation and therefore nutritional adequacy. The aim of this study was to examine the diet of women who lived with children by comparison of hours worked. METHODS: This was a secondary analysis of the Australian National Nutrition and Physical Activity Survey 2011-12. Subjects were women aged 18-65 years who resided with >=1 child (<18 years). Women were grouped according to hours of employment: not working; working <25 h a week; and working >=25 hours a week. Data from two 24-h dietary recalls were used to compare differences between groups in nutrient intake and proportion of energy from discretionary foods. Covariates included were age, education, smoker status, Socio-Economic Indexes for Areas (SEIFA), number of persons in household, week or weekend day of the survey and the sequence of recalls. RESULTS: Analyses included 1869 women. Dietary intakes varied minimally between groups with intakes of fibre, vitamin C, and calcium lowest in the group not working. Overall diet quality was poor with >30% of energy coming from discretionary foods in all groups. CONCLUSIONS: Usual hours of employment per week have a minimal effect on diet quality in women with children. It is likely that different factors specific to each group contribute to the poor dietary intakes and should be further investigated. PMID- 27179939 TI - A distribution analysis of action potential parameters obtained from patch clamped human stem cell-derived cardiomyocytes. AB - We investigated electrophysiological properties of human induced-pluripotent-stem cell-derived and embryonic-stem-cell-derived cardiomyocytes, and analyzed action potential parameters by plotting their frequency distributions. In the both cell lines, the distribution analysis revealed that histograms of maximum upstroke velocity showed two subpopulations with similar intersection values. Sub populations with faster maximum upstroke velocity showed significant prolongation of action potential durations by application of E-4031, whereas others did not, which may be partly due to shallower maximum diastolic potentials. We described electrophysiological and pharmacological properties of stem-cell-derived cardiomyocytes in the respective sub-populations, which provides a way to characterize diverse electrical properties of stem-cell-derived cardiomyocytes systematically. PMID- 27179937 TI - Systemic injection of the DAD1 antagonist SCH 23390 reduces saccharin seeking in rats. AB - Conditioned cues can elicit drug- and sucrose-seeking behaviors that have been shown to depend on dopamine (DA) D1 receptors. If DAD1 receptors are also involved in seeking behavior in general, blocking these receptors should reduce seeking behavior for a non-caloric, non-drug of abuse reinforcer such as saccharin. Forty-six male Long-Evans rats lever pressed for 0.3% saccharin solution 1 h/day for 10 days. A lever response also activated a tone plus a white stimulus light. This compound stimulus lasted for 5 s. After 1 day of forced abstinence, rats received systemic (0, 1, or 10 MUg/kg IP; n = 15-16 per group) injections of SCH 23390 15 min prior to extinction testing. Systemic SCH 23390 reduced saccharin seeking evidenced by a significant reduction in active lever responding and a significant reduction in the number of active lever-contingent deliveries of the tone + light cue following pretreatment with 10 MUg/kg SCH 23390. The slope of responding across the Test session in this group was also significantly steeper, indicating that SCH 23390 may have reduced the persistence of saccharin seeking. The results indicate that DAD1 receptors are involved in saccharin seeking and generalize the previously demonstrated anti-seeking effects of DAD1 antagonism to a non-caloric, non-drug of abuse reinforcer. PMID- 27179938 TI - Validation of a French-Canadian adaptation of the Intuitive Eating Scale-2 for the adult population. AB - Intuitive eating is an adaptive eating style based on the reliance on physiological cues to determine when, what, and how much to eat. The Intuitive Eating Scale-2 (IES-2) is a validated four-subscale tool measuring the degree of adherence to intuitive eating principles. The present series of studies aimed at evaluating the psychometric properties of a French-Canadian adaptation of the IES 2 for the adult population. The factor structure, the reliability (internal consistency and test-retest), the construct validity, and the discriminant validity were evaluated in 334 women and 75 men from the Province of Quebec, Canada, across two studies. A confirmatory factor analysis upheld that the four factor structure of the original IES-2 was adequate for the present sample of French-Canadians. The scale demonstrated adequate internal consistency and test retest reliability. Construct validity evidence was obtained with the significant associations between intuitive eating and psychological and eating-related variables. Intuitive eating was negatively associated with eating disorder symptomatology and with food- and weight-preoccupation, and positively associated with body-esteem and well-being. The French-Canadian IES-2 was also able to discriminate between genders and body mass index categories. The properties of this new version of the IES-2 are demonstrative of a reliable and valid tool to assess intuitive eating in the French-Canadian adult population of the Province of Quebec. PMID- 27179940 TI - Association of sociodemographic and environmental factors with the mental health status among preschool children-Results from a cross-sectional study in Bavaria, Germany. AB - AIM: It has been reported that a great proportion of mental health disorders have an origin in early childhood. In order to evaluate factors possibly associated with children's health, the health monitoring units have been established since 2004 in six study regions in Bavaria, Germany. The second health monitoring survey, implemented in 2005-06, focuses on the mental health status of preschool children. The goal of this study is (1) to examine the association of sociodemographic and environmental factors with mental health and (2) to analyze the applicability of the results of the health monitoring units to all preschool children in Bavaria by calculating weighting factors. METHODS: Data on 6206 preschool children are available. Logistic regression analysis is applied to analyze possible associations with mental health. A weighting method is applied to correct for deviances compared to the whole population of preschool children in Bavaria (N=132,783). RESULTS: 11% of preschool children show mental health problems. Regarding different indicators of sociodemographic status, low household income [unadjusted OR 3.34, 95% CI: 2.23-4.98] shows the strongest association of mental health problems. Non-accessibility of green space [unadjusted OR 2.74, 95% CI: 1.87-4.00] is also strongly associated with mental health. The results of the unweighted and weighted analysis are similar. CONCLUSION: Our findings suggest that sociodemographic status and factors in the living environment show associations with mental health of children. Based on the results of the unweighted and weighted analyses, the second health monitoring analysis shows little deviances compared to data of all Bavarian preschool children. Therefore, the results can be compared to all Bavarian preschool children. PMID- 27179942 TI - Erratum to "Bortezomib for Refractory Autoimmunity in Pediatrics" [Biol Blood Marrow Transplant 2014;20(10):1654-1659]. PMID- 27179941 TI - Gender-specific linkages of parents' childhood physical abuse and neglect with children's problem behaviour: evidence from Japan. AB - BACKGROUND: Childhood abuse has far-reaching effects, not only for survivors of maltreatment but also for subsequent generations. However, the mechanism of such intergenerational linkages has not been fully explored. This study investigated this linkage with special reference to its gender-specific features. METHODS: A dataset of parents and their children, obtained from a cross-sectional survey in the Tokyo metropolitan area of Japan, was used. The study sample consisted of 1750 children aged between 2 and 18 years (865 daughters and 885 sons) and their parents (1003 mothers and fathers). Regression models were estimated to assess the associations among 1) both parents' childhood physical abuse and neglect (childhood abuse), 2) parents' psychological distress, as measured by the Kessler Psychological Distress Scale (K6), and 3) children's problem behaviour, as measured by the clinical scales of the Child Behavior Checklist. RESULTS: Daughters' problem behaviour was more closely associated with mothers' than fathers' childhood abuse, whereas sons' problem behaviour was more closely associated with their fathers' experience. The impact of mothers' childhood abuse on daughters' problem behaviour was mediated at a rate of around 40 % by both parents' psychological distress. The proportion of the effect mediated by parents' psychological distress was less than 20 % for the impact of fathers' childhood abuse on sons' problem behaviour. CONCLUSION: The intergenerational impact of parental childhood abuse on children's problem behaviour is gender specific, i.e. largely characterized by the same gender linkages. Further studies that explore the mechanisms involved in the intergenerational impact of childhood abuse are needed. PMID- 27179943 TI - Erratum to "Salivary Gland Involvement in Chronic Graft-versus-Host Disease: Prevalence, Clinical Significance, and Recommendations for Evaluation" [Biol Blood Marrow Transplant 16:1362-1369]. PMID- 27179945 TI - Editorial Comment. PMID- 27179946 TI - Editorial Comment. PMID- 27179944 TI - Efficacy of transcranial direct-current stimulation (tDCS) in women with provoked vestibulodynia: study protocol for a randomized controlled trial. AB - BACKGROUND: Provoked vestibulodynia is the most common form of vulvodynia. Despite its high prevalence and deleterious sexual, conjugal, and psychological repercussions, effective evidence-based interventions for provoked vestibulodynia remain limited. For a high proportion of women, significant pain persists despite the currently available treatments. Growing evidence suggests that the central nervous system (CNS) could play a key role in provoked vestibulodynia; thus, treatment targeting the CNS, rather than localized dysfunctions, may be beneficial for women suffering from provoked vestibulodynia. In this study, we aim to build on the promising results of a previous case report and evaluate whether transcranial direct-current stimulation, a non-invasive brain stimulation technique targeting the CNS, could be an effective treatment option for women with provoked vestibulodynia. METHODS/DESIGN: This single-center, triple-blind, parallel group, randomized, controlled trial aims to compare the efficacy of transcranial direct-current stimulation with sham transcranial direct-current stimulation in women with provoked vestibulodynia. Forty women diagnosed with provoked vestibulodynia by a gynecologist, following a standardized treatment protocol, are randomized to either active transcranial direct-current stimulation treatment for ten sessions of 20 minutes at an intensity of 2 mA or sham transcranial direct-current stimulation over a 2-week period. Outcome measures are collected at baseline, 2 weeks after treatment and at 3-month follow-up. The primary outcome is pain during intercourse, assessed with a numerical rating scale. Secondary measurements focus on the sexual function, vestibular pain sensitivity, psychological distress, treatment satisfaction, and the patient's global impression of change. DISCUSSION: To our knowledge, this study is the first randomized controlled trial to examine the efficacy of transcranial direct current stimulation in women with provoked vestibulodynia. Findings from this trial are expected to provide significant information about a promising intervention targeting the centralization of pain in women with provoked vestibulodynia. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02543593 . Registered on September 4, 2015. PMID- 27179947 TI - Author Reply. PMID- 27179948 TI - p65 down-regulates DEPTOR expression in response to LPS stimulation in hepatocytes. AB - DEPTOR, a novel endogenous inhibitor of mTOR, plays an important role in regulating the inflammatory response in vascular endothelial cells (ECs) and in mouse skeletal muscle. However, the regulatory mechanism of DEPTOR transcription and its effects on liver inflammation are unknown presently. Here we reported the role of DEPTOR in regulating inflammatory response in mouse liver-derived Hepa1-6 cells and in a mouse model with LPS-induced hepatic inflammation. The results revealed that DEPTOR over-expression in Hepa1-6 liver cells increased the mRNA levels of the pro-inflammatory cytokines interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1). Contrasting results were observed in Hepa1-6 cells with DEPTOR interference. Treatment Hepa1-6 cells with rapamycin, a specific inhibitor of mTORC1, increased MCP-1 mRNA, but have no significant effect on IL-6 mRNA. DEPTOR expression was down-regulated in Hepa1-6 cells with the treatment of inflammatory stimuli LPS or the over-expression of p65/NF-kappaB, a key inflammatory transcription factor. NF-kappaB antagonist (PDTC) and inhibitor (IkappaBalpha) blocked the effect of LPS on DEPTOR expression. The study in vivo showed that DEPTOR mRNA and protein were significantly reduced in a mouse model with LPS-induced hepatic inflammation, which was accompanied by a concurrent activation of the mTOR signaling pathway. Further, the transcriptional regulation of DEPTOR was explored, which revealed that DEPTOR promoter activity was significantly down-regulated by NF-kappaB. The progressive deletions and mutations demonstrated that the NF-kappaB binding motif situated at -145/-127 region is an essential component required for the DEPTOR promoter activity. Chromatin immunoprecipitation (ChIP) assays determined that p65 can directly interact with the DEPTOR promoter DNA. Those results indicate DEPTOR regulates liver inflammation at least partially via mTORC1 pathway, and is down-regulated by LPS through p65. PMID- 27179949 TI - Genetic variants in chromatin-remodeling pathway associated with lung cancer risk in a Chinese population. AB - Chromatin remodeling complexes utilize the energy of ATP hydrolysis to remodel nucleosomes and have essential roles in transcriptional modulation. Increasing evidences indicate that these complexes directly interact with numerous proteins and regulate the formation of cancer. However, few studies reported the association of polymorphisms in chromatin remodeling genes and lung cancer. We hypothesized that variants in critical genes of chromatin remodeling pathway might contribute to the susceptibility of lung cancer. To validate this hypothesis, we systematically screened 40 polymorphisms in six key chromatin remodeling genes (SMARCA5, SMARCC2, SMARCD2, ARID1A, NR3C1 and SATB1) and evaluated them with a case-control study including 1341 cases and 1982 controls. Logistic regression revealed that four variants in NR3C1 and SATB1 were significantly associated with lung cancer risk after false discovery rate (FDR) correction [For NR3C1, rs9324921: odds ratio (OR)=1.23, P for FDR=0.029; rs12521436: OR=0.85, P for FDR=0.040; rs4912913: OR=1.17, P for FDR=0.040; For SATB1, rs6808523: OR=1.33, P for FDR=0.040]. Combing analysis presented a significant allele-dosage tendency for the number of risk alleles and lung cancer risk (Ptrend<0.001). Moreover, expression quantitative trait loci (eQTL) analysis revealed that these two genes were differently expressed between lung tumor and adjacent normal tissues in the database of The Cancer Genome Atlas (TCGA) (P=0.009 for rs6808523). These findings suggested that genetic variants in key chromatin remodeling genes may contribute to lung cancer risk in Chinese population. Further large and well-designed studies are warranted to validate our results. PMID- 27179950 TI - Preparation of modified-biochar from Laminaria japonica: Simultaneous optimization of aluminum electrode-based electro-modification and pyrolysis processes and its application for phosphate removal. AB - The preparation conditions of electro-modification (current density) and pyrolysis (pyrolysis temperature and heating rate) processes were simultaneously optimized using response surface methodology with the quadratic regression model associated with Box-Behnken design. By numerical optimization, the phosphate adsorption capacity of 245.06mg/g was achieved, corresponding to 99.9% of the predicted values under statistically optimized conditions (current density: 38.78mA/cm(2), pyrolysis temperature: 584.1 degrees C, heating rate: 6.91 degrees C/min). By considering R(2) and three error functions values, the experimental results of adsorption kinetics, and the equilibrium isotherms at different temperatures (10-30 degrees C) showed that predictive pseudo-second-order and Sips isotherm models could adequately interpret the phosphate adsorption process for 'statistically optimized electrically modified'-biochar (SOEM-biochar). The maximum phosphate adsorption capacities of SOEM-biochar were found to be 273.9, 345.1, and 460.3mg/g at 10, 20, and 30 degrees C, respectively, which are higher than that of other adsorbents reported in the literature. PMID- 27179951 TI - Succinic acid production from lignocellulosic hydrolysate by Basfia succiniciproducens. AB - The production of chemicals alongside fuels will be essential to enhance the feasibility of lignocellulosic biorefineries. Succinic acid (SA), a naturally occurring C4-diacid, is a primary intermediate of the tricarboxylic acid cycle and a promising building block chemical that has received significant industrial attention. Basfia succiniciproducens is a relatively unexplored SA-producing bacterium with advantageous features such as broad substrate utilization, genetic tractability, and facultative anaerobic metabolism. Here B. succiniciproducens is evaluated in high xylose-content hydrolysates from corn stover and different synthetic media in batch fermentation. SA titers in hydrolysate at an initial sugar concentration of 60g/L reached up to 30g/L, with metabolic yields of 0.69g/g, and an overall productivity of 0.43g/L/h. These results demonstrate that B. succiniciproducens may be an attractive platform organism for bio-SA production from biomass hydrolysates. PMID- 27179952 TI - Concurrent production of carotenoids and lipid by a filamentous microalga Trentepohlia arborum. AB - During the study of Trentepohlia arborum it became clear that its cells are rich in lipids and carotenoids. Thus, lipid content, composition and fatty acids profiles in individual lipid classes, as well as pigment profiles, responding to different culture conditions, were further investigated. The results showed that the predominant carotenoids and lipid fraction in total lipid in this study was beta-carotene and TAG, respectively. The lipid content increased significantly under high light while nitrogen-replete conditions induced the highest carotenoids content. However, only with a double stress of high light and nitrogen-deficiency it was possible to maximize the productivities of both carotenoids and lipids. Carotenoids (mainly beta-carotene) accounted for ca. 5% of the microalgal lipid under the double stress. Data herein show the potential of T. arborum for the production of both lipids and carotenoids, and hence provide an appropriate way to produce different products from T. arborum. PMID- 27179953 TI - Optimisation of slow-pyrolysis process conditions to maximise char yield and heavy metal adsorption of biochar produced from different feedstocks. AB - The objective of this work was to identify biomass feedstocks and optimum pyrolysis process conditions to produce a biochar capable of adsorbing metals from polluted groundwater. Taguchi experimental design was used to determine the effects of slow-pyrolysis process conditions on char yield and zinc adsorption. Treatments were repeated using six candidate feedstocks (Lolium perenne, Lolium perenne fibre, Miscanthus x giganteus, Salix viminalis, Fraxinus excelsior and Picea sitchensis) and the resultant chars were tested for metal adsorption performance. Chars produced from L. perenne and its extracted fibre displayed the greatest zinc adsorption performance and removed 83.27-92.96% respectively. Optimum process conditions in terms of both char yield and zinc adsorption performance were achieved from slow-pyrolysis at 300 degrees C for 2h using a feedstock with a particle size of less than 1mm. PMID- 27179954 TI - Membrane fouling behavior in anaerobic baffled membrane bioreactor under static operating condition. AB - A novel AnMBR combined with ABR as the anaerobic baffled membrane bioreactor (ABMBR) was developed for membrane fouling mitigation without any turbulence intensifying strategy to reduce the energy consumption further. The filtration time of this system lasted 14-25days under stable condition only with back flushing every 48h. The polysaccharide accounted for 6.85+/-3.1% amount of total filter cake and the protein accounted for 4.12+/-2.1%, which took 79.12% and 11.12% of total area in laser scanning confocal microscope (CLSM) image. After filtration, 83.72+/-10.97% of turbidity, 59.28+/-16.46% of polysaccharide, 16.51% of tryptophan and 37.61% of humic-like substrates were rejected, respectively. The total membrane resistance at the end of each cycle was (4.47+/-0.99)*10(13)m( 1). And the resistance from filter cake was (4.15+/-1.00)*10(13)m(-1), which accounted for of 92.6+/-3.4% of total membrane resistance. PMID- 27179955 TI - Pan-omics analysis of biological data. PMID- 27179956 TI - DEET (N,N-diethyl-meta-toluamide)/PMD (para-menthane-3,8-diol) repellent-treated mesh increases Culicoides catches in light traps. AB - Biting midges (Culicoides spp.) are vectors of bluetongue and Schmallenberg viruses. Treatment of mesh barriers is a common method for preventing insect vectored diseases and has been proposed as a means of limiting Culicoides ingression into buildings or livestock transporters. Assessments using animals are costly, logistically difficult and subject to ethical approval. Therefore, initial screening of test repellents/insecticides was made by applying treatments to mesh (2 mm) cages surrounding Onderstepoort light traps. Five commercial treatments were applied to cages as per manufacturers' application rates: control (water), bendiocarb, DEET/p-menthane-3,8-diol (PMD) repellent, Flygo (a terpenoid based repellent) and lambda-cyhalothrin. The experimental design was a 5 * 5 Latin square, replicated in time and repeated twice. Incongruously, the traps surrounded by DEET/PMD repellent-treated mesh caught three to four times more Obsoletus group Culicoides (the commonest midge group) than the other treatments. A proposed hypothesis is that Obsoletus group Culicoides are showing a dose response to DEET/PMD, being attracted at low concentrations and repelled at higher concentrations but that the strong light attraction from the Onderstepoort trap was sufficient to overcome close-range repellence. This study does not imply that DEET/PMD is an ineffective repellent for Culicoides midges in the presence of an animal but rather that caution should be applied to the interpretation of light trap bioassays. PMID- 27179957 TI - Outcomes of type II endoleaks after endovascular abdominal aortic aneurysm (AAA) repair: a single-center, retrospective study. AB - PURPOSE: This study aims to determine incidence and outcomes of type II endoleaks (T2E) after endovascular abdominal aortic aneurysm repair (EVAR). METHODS: A retrospective review of procedural angiograms, computed tomography angiography, and medical records of 202 patients who underwent EVAR with the Gore Excluder stent graft was performed to determine presence and outcomes of T2E. RESULTS: Median follow-up time for 163 patients meeting inclusion criteria [136 males (83%)] was 24.7 months (range=0.5-85.2 months). T2E occurred in 66/163 patients (40.5%). Aneurysm sac size was unchanged in 32/66 patients (48.5%), decreased in 22/66 (33.3%), and increased in 12/66 (18.2%). No aneurysm ruptures, conversion to open repair, or aneurysm-related deaths occurred. CONCLUSION: T2E are a common occurrence after EVAR, often with benign outcome. However, routine surveillance should be performed, particularly in patients with persistent endoleak or sac growth. PMID- 27179958 TI - Comparison of performance of various tumor response criteria in assessment of sunitinib activity in advanced gastrointestinal stromal tumors. AB - PURPOSE: To compare the performance of various tumor response criteria (TRC) in the assessment of patients with advanced gastrointestinal stromal tumor (GIST) treated with sunitinib after failure of imatinib. METHODS: Sixty-two participants with advanced GIST in two clinical trials received oral sunitinib after prior failure of imatinib (median duration 24 weeks; interquartile range 14-56) and were followed with contrast-enhanced computed tomography at baseline and thereafter at median intervals of 6 weeks (IRQ 6-9). Tumor response was prospectively determined using Response Evaluation Criteria in Solid Tumors (RECIST) 1.0, and retrospectively reassessed for comparison using RECIST 1.1, Choi criteria, and modified Choi (mChoi) criteria using the original target lesions. For mChoi criteria, progressive disease was defined as 20% increase in sum of the longest dimension, similar to RECIST 1.1. Clinical benefit rate (CBR; complete response, partial response, or stable disease >=12 weeks) and progression-free survival were compared between various TRCs using kappa statistics. RESULTS: While partial response as the best response was more frequent by Choi and mChoi criteria (50% each) than RECIST 1.1 (15%) and RECIST 1.0 (13%), CBR was similar between various TRCs (overall CBR 60%-77%, 77%-94% agreement between all TRC pairs). Time to best response was shorter for Choi and mChoi criteria (median 11 weeks each) compared to RECIST 1.1 and RECIST 1.0 (median 25 and 24 weeks, respectively). PFS was similar for RECIST 1.1, RECIST 1.0, and mChoi (median 35 weeks each), and shortest for Choi criteria (median 23 weeks). CONCLUSIONS: CBR was similar among the various TRCs, although Choi criteria led to earlier determination of disease progression. Therefore, RECIST 1.1 and mChoi criteria may be preferred for response assessment in patients with advanced GIST. PMID- 27179959 TI - The efficiency of multiparametric magnetic resonance imaging (mpMRI) using PI RADS Version 2 in the diagnosis of clinically significant prostate cancer. AB - OBJECTIVES: To investigate the efficiency of multiparametric MRI (mpMRI) based on Prostate Imaging Reporting and Data System (PI-RADS) Version 2 (v2) in detecting clinically significant prostate cancer (PCa) and to test the interobserver consistency. METHODS: Based on PI-RADS v2, two radiologists reviewed the images of 372 patients who underwent prostate biopsy and prebiopsy mpMRI. RESULTS: There's significant correlation between higher PI-RADS score and the presence of clinical significant PCa (P<.001). PI-RADS score 3 was the best cutoff point with sensitivity and specificity over 80%. The diagnostic concordance was moderate (kappa=0.478). CONCLUSIONS: PI-RADS v2 demonstrated good accuracy in detecting clinically significant PCa, however the interobserver consistency needs to be improved. PMID- 27179960 TI - Isolated intraventricular hemorrhage after spinal surgery. AB - Intracerebral hemorrhage after spinal surgery is a rare but dreaded complication. The most commonly described form of intracranial hemorrhage after spinal surgery is remote cerebellar hemorrhage (i.e. anatomically distant from the surgical site) (Brockmann MA, Groden C. Remote cerebellar hemorrhage: a review. The Cerebellum 2006;5:64-8); however subdural, subarachnoid, and intraventricular hemorrhage can also occur in combination or isolated (Kaloostian PE, Kim JE, Bydon A, Sciubba DM, Wolinsky JP, Gokaslan ZL, Witham TF. Intracranial hemorrhage after spine surgery. J Neurosurg Spine 2013;19:370-80; Khalatbari MR, Khalatbari J, Moharamzad Y. Intracranial hemorrhage following lumbar spine surgery. Eur Spine J 2012;21:2092-96). Isolated intraventricular hemorrhage after spinal surgery is extremely rare; to our knowledge, there are only two cases reported in the literature (Kaloostian PE, Kim JE, Bydon A, Sciubba DM, Wolinsky JP, Gokaslan ZL, Witham TF. Intracranial hemorrhage after spine surgery. J Neurosurg Spine 2013;19:370-80; Khalatbari MR, Khalatbari J, Moharamzad Y. Intracranial hemorrhage following lumbar spine surgery. Eur Spine J 2012;21:2092-96). Here, we present a 76-year-old female patient who developed isolated intraventricular hemorrhage after spinal surgery. PMID- 27179961 TI - Neuroinflammation in Alzheimer's disease: Current evidence and future directions. AB - Several attempts have been made to treat Alzheimer's disease (AD) using anti amyloid strategies with disappointing results. It is clear that the "amyloid cascade hypothesis" alone cannot fully explain the neuronal damage in AD, as evidenced both by autopsy and imaging studies. Neuroinflammation plays a significant role in neurodegenerative diseases, whereas the debate is ongoing about its precise role, whether it is protective or harmful. In this review, we focus on the potential mechanism of glial activation and how local and systemic factors influence disease progression. We focus on neuroinflammation in AD, especially in the earliest stages, a vicious cycle of glial priming, release of pro-inflammatory factors, and neuronal damage. We review the evidence from imaging studies, regarding the temporal relationship between amyloid deposition and neuroinflammation, the influence of systemic inflammation on glial activation, both in acute and chronic stimulation and the relevance of inflammation as a diagnostic and therapeutic target. PMID- 27179962 TI - Severe pulmonary arterial hypertension: stratification of medical therapies, mechanical support, and lung transplantation. AB - Severe pulmonary hypertension is recognized by focusing on the clinical signs and tests that demonstrate decompensated right ventricular failure or, in the worst case scenario, shock. An aggressive treatment regimen including a prostacyclin infusion is required for these patients. Once admitted to the hospital, or the ICU for decompensated right ventricular failure, the short- and long-term outcomes for PAH patients are poor. For those who are candidates, urgent lung transplantation, or extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation may be rescue therapy. PMID- 27179963 TI - DDR1 enhances invasion and metastasis of gastric cancer via epithelial mesenchymal transition. AB - In this study, we investigated the effects of DDR1 on the invasion and metastasis in gastric cancer (GC) via epithelial-mesenchymal transition (EMT). Immunohistochemistry analysis was used to detect DDR1, E-cadherin, and Vimentin expression in GC tissues as well as DDR1 expression in GC cell lines and normal gastric epithelial cells. The relationship between DDR1 expression and EMT in GC cell lines was explored by down and upregulating DDR1 and examining corresponding changes in the expression of EMT-related proteins and in biological characteristics. Furthermore, a nude mice model with a transplantation tumor generating from stably transfected GC cells with DDR1 overexpression was established and performed to further reveal the effects of DDR1 expression on cellular morphology and growth of GC. Our results showed that DDR1 was highly expressed in GC tissues and cell lines compared with adjacent tissues and normal cell line, and its expression was significantly higher in GC having poor differentiation (p < 0.01), advanced depth of wall invasion (p = 0.020), lymph node metastasis (p = 0.0001), liver metastasis (p < 0.01), and high TNM stage (p < 0.01). Western blot analyses revealed that DDR1 overexpression resulted in a significant decrease in the expression of E-cadherin (p < 0.01) and an increase in the expression of Vimentin and Snail (p < 0.01), while knockdown of DDR1 led to opposite outcomes. We further demonstrated that DDR1 overexpression promoted GC cell proliferation (p < 0.05), migration (p < 0.01), and invasion (p < 0.01), and accelerated the growth (p < 0.05) as well as the microvessel formation (p < 0.01) of transplantation tumor in nude mice. Our study establishes that DDR1 enhances invasion and metastasis of gastric cancer via EMT. PMID- 27179966 TI - Low frontal serotonin 2A receptor binding is a state marker for schizophrenia? AB - Here we imaged serotonin 2A receptor (5-HT2AR) binding in a very rare population of monozygotic twins discordant for schizophrenia to provide insight into trait and state components in brain 5-HT2AR patterns. In four twin pairs not medicated with drugs that target 5-HT2AR, frontal 5-HT2AR binding was consistently lower (33%) in schizophrenic- relative to their healthy co-twins. Our results strongly imply low frontal 5-HT2AR availability as a state feature of schizophrenia. If replicated, ideally in a larger sample also including dizygotic twin pairs and drug-naive patients, this finding critically advance our understanding of the complex pathophysiology of schizophrenia. PMID- 27179967 TI - Effective mitigation of tumor lysis syndrome with gradual venetoclax dose ramp, prophylaxis, and monitoring in patients with chronic lymphocytic leukemia. PMID- 27179964 TI - Significance of oncogenes and tumor suppressor genes in AML prognosis. AB - Acute myeloid leukemia (AML) is a heterogeneous disorder among hematologic malignancies. Several genetic alterations occur in this disease, which cause proliferative progression, reducing differentiation and apoptosis in leukemic cells as well as increasing their survival. In the genetic study of AML, genetic translocations, gene overexpression, and mutations effective upon biology and pathogenesis of this disease have been recognized. Proto-oncogenes and tumor suppressor genes, which are important in normal development of myeloid cells, are involved in the regulation of cell cycle and apoptosis, undergo mutation in this type of leukemia, and are effective in prognosis of AML subtypes. This review deals with these genes, the assessment of which can be important in the diagnosis and prognosis of patients as well as therapeutic outcome. PMID- 27179965 TI - Insulin Resistance of Puberty. AB - Puberty is a time of considerable metabolic and hormonal change. Notably, puberty is associated with a marked decrease in insulin sensitivity, on par with that seen during pregnancy. In otherwise healthy youth, there is a nadir in insulin sensitivity in mid-puberty, and then it recovers at puberty completion. However, there is evidence that insulin resistance (IR) does not resolve in youth who are obese going into puberty and may result in increased cardiometabolic risk. Little is known about the underlying pathophysiology of IR in puberty, and how it might contribute to increased disease risk (e.g., type 2 diabetes). In this review, we have outlined what is known about the IR in puberty in terms of pattern, potential underlying mechanisms and other mediating factors. We also outline other potentially related metabolic changes that occur during puberty, and effects of underlying insulin resistant states (e.g., obesity) on pubertal changes in insulin sensitivity. PMID- 27179968 TI - Shifting the pulsatility by increasing the change in rotational speed for a rotary LVAD using a native heart load control system. AB - We have previously developed a native heart load control system for a continuous flow left ventricular assist device (LVAD) ((EVAHEART(r); Sun Medical) and demonstrated that the rotational speed (RS) in synchronization with the cardiac cycle can alter pulsatility and left ventricular (LV) load under general anesthesia. In this study, we assessed the effects of different levels of increase in RS on pulsatility and LV load in the chronic awake phase. We implanted the EVAHEART via left thoracotomy in 7 normal goats (59.3 +/- 4.6 kg). Two weeks after implantation, we examined the effects of co-pulse mode (increased RS in the systolic phase) and counter-pulse mode (increased RS in the diastolic phase), as well as shifting the change in RS from 250 to 500 rpm, and 750 rpm in both modes on pulsatility and LV load. Pulsatility was assessed using pulse pressure and mean dP/dt max of aortic pressure. LV load was assessed using stroke work and left ventricle end-diastolic volume determined from LV pressure-volume loops. In the co-pulse mode, pulsatility values increased as the change in RS increased. By contrast, in the counter-pulse mode, these values decreased as the change in RS increased. LV load increased significantly in the co-pulse mode compared with the counter-pulse mode, but there were no significant differences among the three levels of RS increase in either mode. Increasing RS to varying degrees with our newly developed system could contribute to pulsatility. However, it appeared to have little effect on LV load in normal hearts. PMID- 27179970 TI - A case of severe NSAID exacerbated respiratory disease (NERD) following a dental procedure in a child. AB - BACKGROUND: An allergic reaction following a dental procedure is a rare event. A local anaesthetic (LA) may initially be suspected as a causative agent but allergy to dental LA solutions is extremely rare. CASE REPORT: This report concerns a 13 year old child who underwent dental treatment and was exposed to Lignospan Special((r)) LA, mouthwash, latex gloves, ibuprofen medication, and a Magnum((r)) (almond) ice cream all within 45 min. He subsequently developed acute symptoms of nasal rhinorrhoea, facial flushing, peri-orbital and lip angioedema, followed by throat tightness and wheeze (respiratory compromise). His acute reaction was treated by his medical practitioner with oral anti-histamines, steroid and nebulised salbutamol. The child was referred to a local allergist. The child underwent detailed allergic investigations including skin prick tests, blood tests, incremental local anaesthetic challenge and ibuprofen challenge. The patient was diagnosed with NSAID exacerbated respiratory disease (NERD), a hypersensitivity reaction to ibuprofen. FOLLOW-UP: The patient was advised to avoid NSAIDs and to wear a medic-alert (allergy) bracelet. A detailed written report was sent to the patient's dentist and GP. CONCLUSIONS: In the context of a suspected reaction post dental procedure, local anaesthetic should be considered a possible allergen but other important considerations include analgesics, antibiotics, and latex. All genuine allergic reactions need to be investigated. This report highlights NERD as a possible adverse outcome following dental treatment. PMID- 27179969 TI - N (6)-Methyladenosine (m(6)A) Methylation in mRNA with A Dynamic and Reversible Epigenetic Modification. AB - N (6)-methyladenosine (m(6)A) is the most abundant and reversible internal modification ubiquitously occurring in eukaryotic mRNA, albeit the significant biological roles of m(6)A methylation have remained largely unclear. The well known DNA and histone methylations play crucial roles in epigenetic modification of biologic processes in eukaryotes. Analogously, the dynamic and reversible m(6)A RNA modification, which is installed by methyltransferase (METTL3, METTL14, and WTAP), reversed by demethylases (FTO, ALKBH5) and mediated by m(6)A-binding proteins (YTHDF1-3, YTHDC1), may also have a profound impact on gene expression regulation. Recent discoveries of the distributions, functions, and mechanisms of m(6)A modification suggest that this methylation functionally modulates the eukaryotic transcriptome to influence mRNA transcription, splicing, nuclear export, localization, translation, and stability. This reversible mRNA methylation shed light on a new dimension of post-transcriptional regulation of gene expression at the RNA level. m(6)A methylation also plays significant and broad roles in various physiological processes, such as development, fertility, carcinogenesis, stemness, early mortality, meiosis and circadian cycle, and links to obesity, cancer, and other human diseases. This review mainly describes the current knowledge of m(6)A and perspectives on future investigations. PMID- 27179971 TI - Increased levels of hyper-stable protein aggregates in plasma of older adults. AB - Proteins that misfold into hyper-stable/degradation-resistant species during aging may accumulate and disrupt protein homeostasis (i.e., proteostasis), thereby posing a survival risk to any organism. Using the method diagonal two dimensional (D2D) SDS-PAGE, which separates hyper-stable SDS-resistant proteins at a proteomics level, we analyzed the plasma of healthy young (<30 years) and older (60-80 years) adults. We discovered the presence of soluble SDS-resistant protein aggregates in the plasma of older adults, but found significantly lower levels in the plasma of young adults. We identified the inflammation-related chaperone protein haptoglobin as the main component of the hyper-stable aggregates. This observation is consistent with the growing link between accumulations of protein aggregates and aging across many organisms. It is plausible higher amounts of SDS-resistant protein aggregates in the plasma of older adults may reflect a compromise in proteostasis that may potentially indicate cellular aging and/or disease risk. The results of this study have implications for further understanding the link between aging and the accumulation of protein aggregates, as well as potential for the development of aging-related biomarkers. More broadly, this novel application of D2D SDS-PAGE may be used to identify, quantify, and characterize the degradation-resistant protein aggregates in human plasma or any biological system. PMID- 27179973 TI - Patient education as empowerment and self-rebiasing. AB - The fiduciary nature of the patient-physician relationship requires clinicians to act in the best interest of their patients. Patients are vulnerable due to their health status and lack of medical knowledge, which makes them dependent on the clinicians' expertise. Competent patients, however, may reject the recommendations of their physician, either refusing beneficial medical interventions or procedures based on their personal views that do not match the perceived medical indication. In some instances, the patients' refusal may jeopardize their health or life but also compromise the clinician's moral responsibility to promote the patient's best interests. In other words, health professionals have to deal with patients whose behavior and healthcare decisions seem counterproductive for their health, or even deteriorate it, because of lack of knowledge, bad habits or bias without being the patients' free voluntary choice. The moral dilemma centers on issues surrounding the limits of the patient's autonomy (rights) and the clinician's role to promote the well-being of the patient (duties). In this paper we argue that (1) the use of manipulative strategies, albeit considered beneficent, defeats the purpose of patient education and therefore should be rejected; and (2) the appropriate strategy is to empower patients through patient education which enhances their autonomy and encourages them to become full healthcare partners as opposed to objects of clinical intervention or entities whose values or attitudes need to be shaped and changed through education. First, we provide a working definition of the concept of patient education and a brief historical overview of its origin. Second, we examine the nature of the patient-physician relationship in order to delineate its boundaries, essential for understanding the role of education in the clinical context. Third, we argue that patient education should promote self-rebiasing, enhance autonomy, and empower patients to determine their therapeutic goals. Finally, we develop a moral framework for patient education. PMID- 27179972 TI - Impact of sex and APOE4 on cerebral amyloid angiopathy in Alzheimer's disease. AB - Cerebral amyloid angiopathy (CAA) often coexists with Alzheimer's disease (AD). APOE4 is a strong genetic risk factor for both AD and CAA. Sex-dependent differences have been shown in AD as well as in cerebrovascular diseases. Therefore, we examined the effects of APOE4, sex, and pathological components on CAA in AD subjects. A total of 428 autopsied brain samples from pathologically confirmed AD cases were analyzed. CAA severity was histologically scored in inferior parietal, middle frontal, motor, superior temporal and visual cortexes. In addition, subgroups with severe CAA (n = 60) or without CAA (n = 39) were subjected to biochemical analysis of amyloid-beta (Abeta) and apolipoprotein E (apoE) by ELISA in the temporal cortex. After adjusting for age, Braak neurofibrillary tangle stage and Thal amyloid phase, we found that overall CAA scores were higher in males than females. Furthermore, carrying one or more APOE4 alleles was associated with higher overall CAA scores. Biochemical analysis revealed that the levels of detergent-soluble and detergent-insoluble Abeta40, and insoluble apoE were significantly elevated in individuals with severe CAA or APOE4. The ratio of Abeta40/Abeta42 in insoluble fractions was also increased in the presence of CAA or APOE4, although it was negatively associated with male sex. Levels of insoluble Abeta40 were positively associated with those of insoluble apoE, which were strongly influenced by CAA status. Pertaining to insoluble Abeta42, the levels of apoE correlated regardless of CAA status. Our results indicate that sex and APOE genotypes differentially influence the presence and severity of CAA in AD, likely by affecting interaction and aggregation of Abeta40 and apoE. PMID- 27179974 TI - Cryopreservation of lar gibbon semen collected by manual stimulation. AB - We confirmed ejaculation as a result of manual stimulation in a lar gibbon, and attempted to cryopreserve the semen using TES-Tris-egg yolk-based (TTE) extender. After measuring the amount of semen (g), we first diluted the semen with TTE extender, and calculated sperm concentration (sperm/ml), total sperm count (sperm), and progressive sperm motility (%). Then, we cooled diluted semen slowly to 4 degrees C over 2 h, and added an equal volume of secondary extender containing glycerol over 30 min. Finally, we flash-froze the semen solution by plunging into liquid nitrogen. In addition, we freeze-thawed the solution to determine the recovery rate of the motile sperm. Collection of semen was successful on four of the five occasions. The median (min-max) quantity of ejaculate was 0.19 g (0.09-0.26 g), the median sperm concentration was 1.38 * 10(9) sperm/ml (1.20-1.53 * 10(9) sperm/ml), and the median total sperm count was 0.26 * 10(9) sperm (0.11-0.40 * 10(9) sperm). Moreover, the median sperm motility immediately after ejaculation was 65 % (60-75 %), the median sperm motility after freeze-thawing was 30 % (25-35 %), and the median recovery rate was 42.3 % (40.0 58.3 %). We were able to (1) collect semen from a lar gibbon by manual stimulation, (2) reveal andrological findings regarding semen characteristics, and (3) preserve the genetic resource using TTE cryopreservation. PMID- 27179975 TI - Role of UCP2 in the protective effects of PPARbeta/delta activation on lipopolysaccharide-induced endothelial dysfunction. AB - Bacterial endotoxin lipopolysaccharide (LPS) activates inflammatory pathways, induces cytokine expression in the endothelium, augments reactive oxygen species (ROS) production in the vascular wall, and induces endothelial dysfunction. The aim of the present study was to analyze the effects of peroxisome proliferator activated receptor (PPAR)beta/delta activation on LPS-induced inflammation, oxidative stress and endothelial dysfunction and to determine whether uncoupling protein-2 (UCP2) plays a role in these effects. In vivo, the PPARbeta/delta agonist GW0742 treatment prevented the LPS-induced reduction in aortic relaxation, the increase in vascular ROS production, the upregulation of NOX1, NOX2, p47(phox), and p22(phox) mRNA levels, and the endoplasmic reticulum (ER) stress markers in mice. We show that in mouse aortic endothelial cells (MAECs), GW0742 prevented the decreased A23187-stimulated nitric oxide (NO) production, and the increased intracellular ROS levels caused by exposure to LPS in vitro. The PPARbeta/delta antagonist GSK0660 abolished all these in vivo and in vitro protective effects induced by GW0742. This agonist also restored the reduced expression of UCP2 and mitofusin-2 induced by LPS. The effects of GW0742 on NO and ROS production in MAEC exposed to LPS were abolished by the UCP2 inhibitor genipin or by siRNA targeting UCP-2. Genipin also suppressed the expressional changes on NADPH oxidase and ER stress markers induced by GW0742. In conclusion, PPARbeta/delta activation restored the LPS-induced endothelial dysfunction by upregulation of UCP2, with the subsequent alleviation of ER stress and NADPH oxidase activity, thus reducing intracellular ROS production and increasing NO bioavailability. PMID- 27179977 TI - Endo ICG videoangiography: localizing the carotid artery in skull-base endonasal approaches. AB - BACKGROUND: In this work, the applicability of ICG-VA to skull base endoscopic surgery and its capacity to locate the internal carotid artery are shown. METHODS: An adapted optical module to perform ICG-VA was used to perform endoscopic procedures. There were two intraoperative phases of interest that were used to evaluate the ICA: upon exposure of the skull base and during the intradural exploration. This new tool for obtaining ICA images in real time (as opposed to with navigation), and it is demonstrated that this tool provides a superior ability to detect the margins of the ICA compared with the Doppler technique. On the other hand, the present technique also provides enhancement of the artery through the bone of the skull base without the need for drilling. CONCLUSIONS: ICG-VA is a safe and effective technique for locating the ICA in skull-base expanded endonasal surgery. Furthermore, this technique can provide real-time guidance for the surgeon and increase safety for the patient. PMID- 27179976 TI - Adipose extracellular matrix remodelling in obesity and insulin resistance. AB - The extracellular matrix (ECM) of adipose tissues undergoes constant remodelling to allow adipocytes and their precursor cells to change cell shape and function in adaptation to nutritional cues. Abnormal accumulation of ECM components and their modifiers in adipose tissues has been recently demonstrated to cause obesity-associated insulin resistance, a hallmark of type 2 diabetes. Integrins and other ECM receptors (e.g. CD44) that are expressed in adipose tissues have been shown to regulate insulin sensitivity. It is well understood that a hypoxic response is observed in adipose tissue expansion during obesity progression and that hypoxic response accelerates fibrosis and inflammation in white adipose tissues. The expansion of adipose tissues should require angiogenesis; however, the excess deposition of ECM limits the angiogenic response of white adipose tissues in obesity. While recent studies have focused on the metabolic consequences and the mechanisms of adipose tissue expansion and remodelling, little attention has been paid to the role played by the interaction between peri adipocyte ECM and their cognate cell surface receptors. This review will address what is currently known about the roles played by adipose ECM, their modifiers, and ECM receptors in obesity and insulin resistance. Understanding how excess ECM deposition in the adipose tissue deteriorates insulin sensitivity would provide us hints to develop a new therapeutic strategy for the treatment of insulin resistance and type 2 diabetes. PMID- 27179978 TI - Flatness of the infratentorial space associated with hemifacial spasm. AB - BACKGROUND: Whether a difference in morphology of the infratentorial space is associated with hemifacial spasm is not well understood. The aim of this study was to analyze the three-dimensional conformation of the infratentorial space and evaluate any possible contribution of morphological characteristics to the development of neurovascular compression leading to hemifacial spasm. METHODS: We enrolled 25 patients with hemifacial spasm and matched them by age and sex to controls. The extent of the three-dimensional axes and the volume of the infratentorial space were measured using image analysis software for three dimensional MRI. We evaluated the correlation between a morphological difference in the infratentorial space and changes in vascular configuration in the brain stem. RESULTS: We found no statistical difference in volumetric analyses. The mean aspect ratio on the coronal plane (the ratio of the Z to X extent) of the infratentorial space in patients with hemifacial spasm was significantly lower (p < 0.01) than that in controls, as was the mean aspect ratio on the sagittal plane (the ratio of Z to Y extent, p < 0.01). A smaller sagittal aspect ratio was correlated (p < 0.05) with greater lateral deviation of the basilar artery. CONCLUSIONS: Our results suggest that flatness of the superior-inferior dimension of the infratentorial space is an anatomical feature that characterizes patients with hemifacial spasm. We hypothesize that this unique structural variation may exaggerate the lateral deviation of the vertebrobasilar arteries due to arteriosclerosis and exacerbate the space competition among vessels and cranial nerves. PMID- 27179979 TI - Preoperative nomogram for prediction of microscopic parametrial infiltration in patients with FIGO stage IB cervical cancer treated with radical hysterectomy. AB - OBJECTIVE: This study aimed to establish a nomogram to predict microscopic parametrial infiltration (PMI) by combining preoperative clinicopathologic factors in FIGO stage IB cervical cancer patients treated by radical hysterectomy (RH). METHODS: We retrospectively analyzed clinicopathologic data of 298 patients with FIGO stage IB cervical cancer treated by RH between February 2000 and March 2015. The nomogram was developed based on multivariate logistic regression analysis of preoperative clinicopathologic data. The accuracy and discriminative ability of the nomogram were evaluated by a concordance index and calibration curve. The low-risk group was predefined as having a predicted probability of PMI <10%. RESULTS: Multivariate analysis identified diameter-based tumor volume and disruption of the cervical stromal ring on magnetic resonance imaging, serum squamous cell carcinoma antigen level, and menopausal status as independent prognostic factors associated with PMI. The concordance index of the nomogram was 0.940 (95% CI, 0.908-0.967), and calibration plots revealed good agreement between the observed probabilities and nomogram-predicted probabilities (Hosmer Lemeshow test, p=0.574). The nomogram classified 200 out of 298 patients (67.1%) as low risk. In the low-risk group, the predicted probability of PMI was 3.5% and the actual PMI rate was 2.5% (5 out of 200). CONCLUSIONS: We developed a preoperative nomogram predicting microscopic PMI in surgically treated FIGO stage IB cervical cancer patients. The probabilities derived from this nomogram may have the potential to provide valuable guidance for physicians regarding the primary management of FIGO stage IB cervical cancer patients. PMID- 27179980 TI - Superior Limbic Keratoconjunctivitis-like Inflammation in Patients with Chronic Graft-Versus-Host Disease. AB - PURPOSE: Describe the presentation and management of superior limbic keratoconjunctivitis (SLK)-like inflammation and secondary limbal stem cell dysfunction in the setting of ocular chronic graft-versus-host disease (cGVHD). METHODS: Retrospective observational case series in a multicenter clinical practice. Participants were 13 patients (26 eyes) with ocular cGVHD and SLK-like inflammation presenting to the University of Illinois at Chicago and BostonSight(r) between January 1, 2009 and July 1, 2013. MAIN OUTCOME MEASURES: 1) Reversal or worsening of SLK, and 2) development of limbal stem cell dysfunction. RESULTS: All eyes showed evidence of SLK-like inflammation and superior limbal stem cell dysfunction manifested by conjunctival injection and superior conjunctival and corneal staining. In addition to aggressive lubrication, management strategies for SLK included topical steroids (20/26), punctal occlusion (18/26), topical cyclosporine (24/26), autologous serum tears (12/26), therapeutic soft contact lens (13/26 eyes) and scleral lenses (4/26 eyes). SLK and limbal stem cell dysfunction were reversed in 23/26 eyes. Three eyes of two patients with long-standing disease demonstrated frank limbal stem cell deficiency (LSCD) and corneal pannus, with one patient requiring multiple reconstructive surgical procedures. CONCLUSIONS: SLK-like inflammation is an under-recognized condition in patients with severe dry eyes secondary to ocular cGVHD. Untreated SLK can potentially lead to permanent LSCD over time. Early recognition and management of SLK in ocular cGVHD can improve vision, reverse signs, and may prevent these long-term consequences. PMID- 27179981 TI - Management of Carotid Bifurcation Tumors: 30-Year Experience. AB - BACKGROUND: The carotid bifurcation can host a variety of tumors requiring complex surgical management. Treatment requires resection and, in some cases, vascular reconstruction that may compromise the cerebral circulation. The most frequent lesion at this location is the carotid body tumor (CBT). CBT are classified according to Shamblin in 3 types depending on the degree of carotid vessels encasement. Our main objective was to report our clinical experience managing carotid bifurcation tumors throughout the last 30 years. METHODS: Between 1984 and 2014, we treated 30 patients with 32 carotid bifurcation tumors. There were 21 women and 9 men (2.3:1), with a mean age of 45.5 years (18-75). The most frequent presentation was an asymptomatic neck swelling or palpable mass localized at the carotid triangle (86.7%). RESULTS: Thirty of 32 tumors were resected. Since 1994, computed tomography scan has been the most frequently used diagnostic imaging tool (80%), followed by magnetic resonance imaging. Angiography was used mainly during the first 10 years of the study period. Mean size of the tumor was 44.6 mm (20-73 mm). Nineteen (63%) were classified as Shamblin II and 6 (20%) as Shamblin's III. All specimens were analyzed by a pathologist; 28 tumors (93%) were confirmed as paragangliomas, 2 (7%) were diagnosed as schwannomas. Two patients underwent preoperative embolization of the CBT; 5 patients (17%) required simultaneous carotid revascularization, all of them Shamblin III. Mean hospitalization time was 4.5 days (1-35 days). Transient extracranial nerve deficit was observed in 7 patients (23.3%). Three patients (Shamblin III) required red blood cells transfusion. One patient (Shamblin III) underwent a planned en bloc excision of the vagus nerve. There was no perioperative mortality or procedure-related stroke. No malignancy or tumor recurrence were observed during follow-up. CONCLUSIONS: CBTs can be diagnosed on clinical grounds requiring vascular imaging confirmation. These infrequent lesions are generally benign. Early surgical removal by surgeons with vascular expertise avoids permanent neurologic and or vascular complications. PMID- 27179982 TI - Outcomes of the Endovascular Treatment of Stenotic Lesions versus Chronic Total Occlusions in the Iliac Sector. AB - BACKGROUND: This study compares outcomes of the endovascular treatment (EVT) of iliac artery occlusive disease according to whether the treated lesion is a stenosis or a chronic total occlusion (CTO). METHODS: Patients undergoing EVT from 2003 to 2013 for iliac artery occlusive disease were identified and the lesions treated stratified into stenotic (Group 1, n = 375) or CTO (Group 2, n = 87). Patients were followed clinically and hemodynamically (thigh-brachial index, TBI). Comorbidities, procedural factors, and outcomes were compared between the 2 groups using Kaplan-Meier, Breslow, and Cox models. RESULTS: Four hundred sixty two iliac endovascular procedures in 378 patients were included in a retrospective study. The 2 groups only differed in preprocedural TBI [0.77 (Group 1) vs. 0.67 (Group 2), P < 0.001], lesion length [39.7 mm (Group 1) vs. 49.9 mm (Group 2), P < 0.001], and the use of a covered stent [11.6% (Group 1) vs. 46.2% (Group 2), P < 0.001]. The technical success rate was higher in Group 1 (99.2% vs. 89.7%, P < 0.001). Five early occlusions were recorded in Group 1 and 3 in Group 2 (1.3% vs. 3.8%, P = 0.146). Median follow-up was 34 months (1-113). At 12 and 36 months, stenotic lesions showed better primary (P1) and secondary (P2) patency rates [P1 93.0% and 85.8% vs. 83.1% and 74.7%, hazard ratio (HR) 1.90 (1.15-3.14), P = 0.018; P2 97.8% and 96.8% vs. 93.0% and 87.4%, HR 2.86 (1.39 5.90), P = 0.007] and freedom from reintervention (FFR) rates [91.6% and 83.5% vs. 84.1% and 78.9%, HR 1.51 (0.90-2.53), P = 0.132]. In a multivariate analysis, CTO showed a worse P2 than stenotic lesions [HR 2.81 (1.17-6.76), P = 0.021], yet no differences emerged in P1 [HR 1.41 (0.76-2.63), P = 0.277] or FFR [HR 1.43 (0.79-2.57), P = 0.237]. A lower preprocedural TBI was correlated with a greater risk of EVT failure in terms of patency and FFR (P < 0.05). The use of a stent shorter than 40 mm emerged as a protective factor with an HR for P1 of 3.68 (1.53 8.87) (P = 0.004). CONCLUSIONS: EVT for iliac artery disease offers good outcomes in terms of long-term patency, although improved results were observed here for the treatment of stenotic lesions over CTO. Procedures performed in patients with a lower TBI and the use of a stent >40 mm were related to a worse stent patency. PMID- 27179983 TI - The Impact of Race on Advanced Chronic Venous Insufficiency. AB - BACKGROUND: The study aimed to determine the association between race and patient variables, hospital covariates, and outcomes in patients presenting with advanced chronic venous insufficiency. METHODS: The National Inpatient Sample was queried to identify all Caucasian and African-American patients with a primary International Classification of Diseases, Ninth Revision (ICD-9) diagnosis code for venous stasis with ulceration (454.0), inflammation (454.1), or complications (454.2) from 1998 to 2011. CEAP scores were correlated with ICD-9 diagnosis. Demographics, CEAP classification, management, cost of care, length of stay (LOS), and inpatient mortality were compared between races. Statistical analysis was via descriptive statistics, Student's t-test, and the Fisher's exact test. Trend analysis was completed using the Mann-Kendall test. RESULTS: A total of 20,648 patients were identified of which 85% were Caucasian and 15% were African American. Debridement procedures had the highest costs at $6,096 followed by skin grafting at $4,089. There was an overall decrease in the number of ulcer debridements, vein stripping, and sclerotherapy procedures between 1998 and 2011 (P < 0.05) for both groups. However, African-American patients had significantly more ulcer debridements than their Caucasian counterparts. CONCLUSIONS: African American patients with a primary diagnosis of venous stasis present with more advanced venous disease at a younger age compared with their Caucasian counterparts. This is associated with increased ulcer debridement, deep vein thrombosis rates and hospital charges in the African-American cohort. There are no differences in sclerotherapy or skin grafting procedures, LOS or inpatient mortality between races. PMID- 27179984 TI - Postoperative Outcomes of Hybrid Repair in the Treatment of Aortic Arch Aneurysms. AB - BACKGROUND: The advent of thoracic endovascular aneurysm repair (TEVAR) has bought about a tremendous revolution in the treatment strategy for aortic arch aneurysms. We reviewed our experience using TEVAR with the hybrid approach in the treatment of aortic arch aneurysms to evaluate its feasibility, safety, and effectiveness. METHODS: Between October 2008 and July 2014, 61 consecutive patients (51 men; mean age 75.8 +/- 7.7 years; range, 43-85 years) underwent elective treatment for aortic arch aneurysms with the hybrid approach. The 61 patients were separated into 2 groups. Thirty-five patients underwent total debranching TEVAR for zone 0 (debranching TEVAR group), 26 patients underwent long elephant trunk (ET) followed by secondary retrograde TEVAR (ET group). Preoperative, perioperative, and follow-up data were collected retrospectively in the database. RESULTS: The technical success rate was 100%. The paraplegia rates in total debranching TEVAR and long ET TEVAR and were 2.9% and 3.8%, respectively. The stroke rates in total debranching TEVAR and long ET TEVAR were 11.4% and 7.7%, respectively. The overall 30-day mortality and in-hospital mortality rates for all 61 patients were 0% and 3.4% (n = 2; both were in the total debranching TEVAR group), respectively. There were no perioperative type 1 or 3 endoleaks that required secondary intervention. The mean hospital stay was 15.8 days. The median follow-up was 309 +/- 303 days. No aneurysm-related deaths occurred during follow-up. CONCLUSIONS: The hybrid approach can be safely performed with good technical success and good midterm results. In future, new alternative devices for aortic arch pathologies, such as a branched stent graft that eliminates extra-anatomic bypass, should be developed. PMID- 27179985 TI - Text mining patents for biomedical knowledge. AB - Biomedical text mining of scientific knowledge bases, such as Medline, has received much attention in recent years. Given that text mining is able to automatically extract biomedical facts that revolve around entities such as genes, proteins, and drugs, from unstructured text sources, it is seen as a major enabler to foster biomedical research and drug discovery. In contrast to the biomedical literature, research into the mining of biomedical patents has not reached the same level of maturity. Here, we review existing work and highlight the associated technical challenges that emerge from automatically extracting facts from patents. We conclude by outlining potential future directions in this domain that could help drive biomedical research and drug discovery. PMID- 27179986 TI - An improved model for fragment-based lead generation at AstraZeneca. AB - Modest success rates in fragment-based lead generation (FBLG) projects at AstraZeneca (AZ) prompted operational changes to improve performance. In this review, we summarize these changes, emphasizing the construction and composition of the AZ fragment library, screening practices and working model. We describe the profiles of the screening method for specific fragment subsets and statistically assess our ability to follow up on fragment hits through near neighbor selection. Performance analysis of our second-generation fragment library (FL2) in screening campaigns illustrates the complementary nature of flat and 3D fragments in exploring protein-binding pockets and highlights our ability to deliver fragment hits using multiple screening techniques for various target classes. The new model has had profound impact on the successful delivery of lead series to drug discovery projects. PMID- 27179987 TI - Current therapies for premature ejaculation. AB - Premature ejaculation (PE) subjectively affects 20-30% of men globally. Until recently, understanding of PE was hampered by the absence of a widely accepted definition, paucity of evidence-based clinical studies, and the absence of an appropriate animal model. Here, we elaborate on the current definition of PE, its pathogenesis, currently available therapies, and future treatment prospects. Most treatments for PE are 'off-label' and include selective serotonin reuptake inhibitors (SSRIs), topical anesthetics, tramadol, and phosphodiesterase type 5 (PDE5) inhibitors. Such knowledge of the benefit and limitations of each treatment will help to direct future drug design and formulations. PMID- 27179989 TI - Development and Validation of Risk Models to Select Ever-Smokers for CT Lung Cancer Screening. AB - IMPORTANCE: The US Preventive Services Task Force (USPSTF) recommends computed tomography (CT) lung cancer screening for ever-smokers aged 55 to 80 years who have smoked at least 30 pack-years with no more than 15 years since quitting. However, selecting ever-smokers for screening using individualized lung cancer risk calculations may be more effective and efficient than current USPSTF recommendations. OBJECTIVE: Comparison of modeled outcomes from risk-based CT lung-screening strategies vs USPSTF recommendations. DESIGN, SETTING, AND PARTICIPANTS: Empirical risk models for lung cancer incidence and death in the absence of CT screening using data on ever-smokers from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO; 1993-2009) control group. Covariates included age; education; sex; race; smoking intensity, duration, and quit-years; body mass index; family history of lung cancer; and self-reported emphysema. Model validation in the chest radiography groups of the PLCO and the National Lung Screening Trial (NLST; 2002-2009), with additional validation of the death model in the National Health Interview Survey (NHIS; 1997-2001), a representative sample of the United States. Models were applied to US ever smokers aged 50 to 80 years (NHIS 2010-2012) to estimate outcomes of risk-based selection for CT lung screening, assuming screening for all ever-smokers, yield the percent changes in lung cancer detection and death observed in the NLST. EXPOSURES: Annual CT lung screening for 3 years beginning at age 50 years. MAIN OUTCOMES AND MEASURES: For model validity: calibration (number of model-predicted cases divided by number of observed cases [estimated/observed]) and discrimination (area under curve [AUC]). For modeled screening outcomes: estimated number of screen-avertable lung cancer deaths and estimated screening effectiveness (number needed to screen [NNS] to prevent 1 lung cancer death). RESULTS: Lung cancer incidence and death risk models were well calibrated in PLCO and NLST. The lung cancer death model calibrated and discriminated well for US ever-smokers aged 50 to 80 years (NHIS 1997-2001: estimated/observed = 0.94 [95%CI, 0.84-1.05]; AUC, 0.78 [95%CI, 0.76-0.80]). Under USPSTF recommendations, the models estimated 9.0 million US ever-smokers would qualify for lung cancer screening and 46,488 (95% CI, 43,924-49,053) lung cancer deaths were estimated as screen-avertable over 5 years (estimated NNS, 194 [95% CI, 187-201]). In contrast, risk-based selection screening of the same number of ever-smokers (9.0 million) at highest 5-year lung cancer risk (>=1.9%) was estimated to avert 20% more deaths (55,717 [95% CI, 53,033-58,400]) and was estimated to reduce the estimated NNS by 17% (NNS, 162 [95% CI, 157-166]). CONCLUSIONS AND RELEVANCE: Among a cohort of US ever-smokers aged 50 to 80 years, application of a risk based model for CT screening for lung cancer compared with a model based on USPSTF recommendations was estimated to be associated with a greater number of lung cancer deaths prevented over 5 years, along with a lower NNS to prevent 1 lung cancer death. PMID- 27179990 TI - Claulansine F promoted the neuronal differentiation of neural stem and progenitor cells through Akt/GSK-3beta/beta-catenin pathway. AB - The persistence of neurogenesis raises the idea that neurons produced by the resident or transplanted neural stem cells could replace the neurons lost from brain injury or neurodegenerative disease. Therefore, compounds or methods for promoting neuronal differentiation become the focus of neurodegenerative disease therapy research. Claulansine F (Clau F), a newly discovered carbazole alkaloid, has been showed to induce neuritogenesis in PC12 cells. Herein, we studied the effect of Clau F on neuronal differentiation of neural stem/progenitor cells (NS/PCs). The current study demonstrated that Clau F initiated neuronal differentiation with a significant increase of TuJ1-positive cells and TuJ1 protein levels. We also found that Clau F promoted the maturity and sustainability of neurons by increasing MAP2-positive cells and MAP2 protein levels. At the same time, Clau F significantly inhibited the proliferation of NS/PCs. The underlying mechanism of Clau F was preliminary explored. Clau F treatment resulted in a profound increase of phosphorylation of Akt and GSK 3beta, which led to GSK-3beta inhibition and subsequently the nuclear accumulation of beta-catenin. Further, the interaction between beta-catenin and p300 in the nucleus was enhanced and the transcription of p300/beta-catenin responsive genes were increased significantly (c-jun, fra-1) by Clau F. Importantly, the positive effect of Clau F on neuronal differentiation was abolished by Akti-1/2, a specific inhibitor of Akt-1/2 kinase, which indicated the involvement of Akt/GSK-3beta in Clau F-mediated neuronal differentiation. In conclusion, these data suggested that Clau F promoted neuronal differentiation through Akt/GSK-3beta/beta-catenin signaling pathway in NS/PCs. PMID- 27179991 TI - Pyr3, a TRPC3 channel blocker, potentiates dexamethasone sensitivity and apoptosis in acute lymphoblastic leukemia cells by disturbing Ca(2+) signaling, mitochondrial membrane potential changes and reactive oxygen species production. AB - Dexamethasone (Dex) is used as a chemotherapeutic drug in the treatment of acute lymphoblastic leukemia (ALL) because of its capacity to induce apoptosis. However, some ALL patients acquire resistance to glucocorticoids (GC). Thus, it is important to explore new agents to overcome GC resistance. The aim of the present work was to assess the ability of Pyr3, a selective inhibitor of transient receptor potential canonical 3 (TRPC3), to sensitize human ALL cells to Dex. We show here, for the first time, that Pyr3 enhances Dex sensitivity through the distraction of Dex-mediated Ca(2+) signaling in ALL cells (in vitro) and primary blasts (ex vivo) associated with mitochondrial-mediated reactive oxygen species production in ALL cells. Pyr3 alone induced Ca(2+) signaling via only endoplasmic reticulum-released Ca(2+) and exerted inhibitory effect on store operated Ca(2+) entry in dose-dependent manner in ALL cell lines. Pre-incubation of cells with Pyr3 significantly curtailed the thapsigargin- and Dex-evoked Ca(2+) signaling in ALL cell lines. Pyr3 synergistically potentiated Dex lethality, as shown by the induction of cell mortality, G2/M cell cycle arrest and apoptosis in ALL cell lines. Moreover, Pyr3 disrupted Dex-mediated Ca(2+) signaling and increased the sensitivity of Dex-induced cell death in primary blasts from ALL patients. Additional analysis showed that co-treatment with Dex and Pyr3 results in mitochondrial membrane potential depolarization and reactive oxygen species production in ALL cells. Together, Pyr3 exhibited potential therapeutic benefit in combination with Dex to inverse glucocorticoid resistance in human ALL and probably in other lymphoid malignancies. PMID- 27179992 TI - Comparison of kinetic and pharmacological profiles of recombinant alpha1gamma2L and alpha1beta2gamma2L GABAA receptors - A clue to the role of intersubunit interactions. AB - The fastest inhibitory mechanism in the CNS is mediated by ionotropic GABAA receptors and it is known that subunit composition critically determines their properties. While a typical GABAA receptor consists of two alpha, two beta and one gamma/delta subunit, there are some exceptions, e.g. alphabeta receptors. Functional alpha1gamma2 GABAA receptors can be expressed in recombinant model (Verdoorn et al., 1990) and although their role remains unknown, it seems appealing to extend their characterization to further explore the structure function relationship of GABAA receptors. Intriguingly, this receptor is lacking canonical GABA binding sites but it can be activated by GABA and dose-response relationships for alpha1beta2gamma2L and alpha1gamma2L receptors overlap. Deactivation kinetics was similar for both receptors but the percentage of the fast component was smaller in the case of alpha1gamma2L receptors and, consequently, the mean deactivation time constant was slower. The rate and extent of macroscopic desensitization were smaller in the case of alpha1gamma2L receptors but they showed slower recovery. Both receptor types had a similar proton sensitivity showing only subtle but significant differences in pH effects on deactivation. Flurazepam exerted a similar effect on both receptors but the rapid deactivation components were differently affected and an opposite effect was observed on desensitization extent. Rebound currents evoked by pentobarbital were undistinguishable for both receptor types. Taking altogether, although some significant differences were found, alpha1beta2gamma2L and alpha1gamma2L receptors showed unforeseen similarity. We propose that functioning of GABAA receptors might rely on subunit-subunit cooperative interactions to a larger extent than believed so far. PMID- 27179988 TI - Effect of Aspirin on Development of ARDS in At-Risk Patients Presenting to the Emergency Department: The LIPS-A Randomized Clinical Trial. AB - IMPORTANCE: Management of acute respiratory distress syndrome (ARDS) remains largely supportive. Whether early intervention can prevent development of ARDS remains unclear. OBJECTIVE: To evaluate the efficacy and safety of early aspirin administration for the prevention of ARDS. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, double-blind, placebo-controlled, randomized clinical trial conducted at 16 US academic hospitals. Between January 2, 2012, and November 17, 2014, 7673 patients at risk for ARDS (Lung Injury Prediction Score >=4) in the emergency department were screened and 400 were randomized. Ten patients were excluded, leaving 390 in the final modified intention-to-treat analysis cohort. INTERVENTIONS: Administration of aspirin, 325-mg loading dose followed by 81 mg/d (n = 195) or placebo (n = 195) within 24 hours of emergency department presentation and continued to hospital day 7, discharge, or death. MAIN OUTCOMES AND MEASURES: The primary outcome was the development of ARDS by study day 7. Secondary measures included ventilator-free days, hospital and intensive care unit length of stay, 28-day and 1-year survival, and change in serum biomarkers associated with ARDS. A final alpha level of .0737 (alpha = .10 overall) was required for statistical significance of the primary outcome. RESULTS: Among 390 analyzed patients (median age, 57 years; 187 [48%] women), the median (IQR) hospital length of stay was 6 3-10) days. Administration of aspirin, compared with placebo, did not significantly reduce the incidence of ARDS at 7 days (10.3% vs 8.7%, respectively; odds ratio, 1.24 [92.6% CI, 0.67 to 2.31], P = .53). No significant differences were seen in secondary outcomes: ventilator-free to day 28, mean (SD), 24.9 (7.4) days vs 25.2 (7.0) days (mean [90% CI] difference, 0.26 [-1.46 to 0.94] days; P = .72); ICU length of stay, mean (SD), 5.2 (7.0) days vs 5.4 (7.0) days (mean [90% CI] difference, -0.16 [-1.75 to 1.43] days; P = .87); hospital length of stay, mean (SD), 8.8 (10.3) days vs 9.0 (9.9) days (mean [90% CI] difference, -0.27 [-1.96 to 1.42] days; P = .79); or 28-day survival, 90% vs 90% (hazard ratio [90% CI], 1.03 [0.60 to 1.79]; P = .92) or 1-year survival, 73% vs 75% (hazard ratio [90% CI], 1.06 [0.75 to 1.50]; P = .79). Bleeding-related adverse events were infrequent in both groups (aspirin vs placebo, 5.6% vs 2.6%; odds ratio [90% CI], 2.27 [0.92 to 5.61]; P = .13). RESULTS: Among 390 analyzed patients (median age, 57 years; 187 [48%] women), median (IQR) hospital length of stay was 6 (3-10) days. Administration of aspirin, compared with placebo, did not significantly reduce the incidence of ARDS at 7 days (OR, 1.24; 92.6%CI, 0.67-2.31). No significant differences were seen in secondary outcomes or adverse events. [table: see text] CONCLUSIONS AND RELEVANCE: Among at-risk patients presenting to the ED, the use of aspirin compared with placebo did not reduce the risk of ARDS at 7 days. The findings of this phase 2b trial do not support continuation to a larger phase 3 trial. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01504867. PMID- 27179993 TI - Parallel development of chromatographic and mass-spectrometric methods for quantitative analysis of glycation on an IgG1 monoclonal antibody. AB - Monitoring post-translational modifications (PTMs) in biotherapeutics is of paramount importance. In pharmaceutical industry, chromatography with optical detection is the standard choice of quantitation of product related impurities; and mass spectrometry is used only for characterization. Parallel development of a boronate affinity chromatographic (BAC) and a mass spectrometric methods for quantitative measurement of glycation on a monoclonal antibody (mAb) shed light on the importance of certain characteristics of the individual methods. Non specific interactions in BAC has to be suppressed with the so-called shielding reagent. We have found that excessive amount of shielding reagents in the chromatographic solvents may cause significant underestimation of glycation. Although contamination of the retained peak with the non-glycated isoforms in BAC is unavoidable, our work shows that it can be characterized and quantitated by mass spectrometry. It has been demonstrated that glycation can be measured by mass spectrometry at the intact protein level with an LOQ value of 3.0% and error bar of +/-0.5%. The BAC and MS methods have been found to provide equivalent results. These methods have not been compared from these points of view before. PMID- 27179994 TI - Analysis of putative resistance gene loci in UK field populations of Haemonchus contortus after 6years of macrocyclic lactone use. AB - Sheep farmers in the UK rely on strategic anthelmintic use to treat and control gastrointestinal roundworms in their flocks. However, resistance to these drugs is now widespread and threatens the sustainability of sheep production. The mechanisms underlying resistance to the most commonly used class, the macrocyclic lactones, are not known and sensitive diagnostic tools based on molecular markers are not currently available. This prohibits accurate surveillance of resistance or assessment of strategies aimed at controlling its spread. In this study, we examined four UK field populations of Haemonchus contortus, differing in macrocyclic lactone treatment history, for evidence of selection at 'candidate gene' loci identified as determining macrocyclic lactone resistance in previously published research. Individual worms were genotyped at Hc-lgc-37, Hc-glc-5, Hc avr-14 and Hc-dyf-7, and four microsatellite loci. High levels of polymorphism were identified at the first three candidate gene loci with remarkably little polymorphism at Hc-dyf-7. While some between-population comparisons of individual farms with and without long-term macrocyclic lactone use identified statistically significant differences in allele frequency and/or fixation index at the Hc-lgc 37, Hc-glc-5 or Hc-avr-14 loci, we found no consistent evidence of selection in other equivalent comparisons. While it is possible that different mechanisms are important in different populations or that resistance may be conferred by small changes at multiple loci, our findings suggest that these are unlikely to be major loci conferring macrocyclic lactone resistance on UK farms or suitable for diagnostic marker development. More powerful approaches, using genome-wide or whole genome sequencing, may be required to define macrocyclic lactone resistance loci in such genetically variable populations. PMID- 27179995 TI - A non-invasive method for studying viral DNA delivery to bacteria reveals key requirements for phage SPP1 DNA entry in Bacillus subtilis cells. AB - Bacteriophages use most frequently a tail apparatus to create a channel across the entire bacterial cell envelope to transfer the viral genome to the host cell cytoplasm, initiating infection. Characterization of this critical step remains a major challenge due to the difficulty to monitor DNA entry in the bacterium and its requirements. In this work we developed a new method to study phage DNA entry that has the potential to be extended to many tailed phages. Its application to study genome delivery of bacteriophage SPP1 into Bacillus subtilis disclosed a key role of the host cell membrane potential in the DNA entry process. An energized B. subtilis membrane and a millimolar concentration of calcium ions are shown to be major requirements for SPP1 DNA entry following the irreversible binding of phage particles to the receptor YueB. PMID- 27179996 TI - Borehole density on the surface of living Porites corals as an indicator of sedimentation in Hong Kong. AB - Borehole density on the surface of Porites has been used as an indicator of water quality in the Great Barrier Reef. We assessed the relationship between borehole density on Porites and eight water quality parameters across 26 sites in Hong Kong. We found that total borehole densities on the surface of Porites at 16 of the studied sites were high (>1000individualsm(-2)), with polychaetes being the dominant bioeroders. Sedimentation rate was correlated positively with total borehole density and polychaete borehole density, with the latter relationship having a substantially higher correlation of determination. None of the environmental factors used were significantly correlated with bivalve borehole density. These results provide a baseline for assessing future changes in coral bioerosion in Hong Kong. This present study also indicates that polychaete boreholes can be used as a bioindicator of sedimentation in the South China Sea region where polychaetes are numerically dominant bioeroders. PMID- 27179997 TI - Variation in the composition of corals, fishes, sponges, echinoderms, ascidians, molluscs, foraminifera and macroalgae across a pronounced in-to-offshore environmental gradient in the Jakarta Bay-Thousand Islands coral reef complex. AB - Substrate cover, water quality parameters and assemblages of corals, fishes, sponges, echinoderms, ascidians, molluscs, benthic foraminifera and macroalgae were sampled across a pronounced environmental gradient in the Jakarta Bay Thousand Islands reef complex. Inshore sites mainly consisted of sand, rubble and turf algae with elevated temperature, dissolved oxygen, pH and chlorophyll concentrations and depauperate assemblages of all taxa. Live coral cover was very low inshore and mainly consisted of sparse massive coral heads and a few encrusting species. Faunal assemblages were more speciose and compositionally distinct mid- and offshore compared to inshore. There were, however, small-scale differences among taxa. Certain midshore sites, for example, housed assemblages resembling those typical of the inshore environment but this differed depending on the taxon. Substrate, water quality and spatial variables together explained from 31% (molluscs) to 72% (foraminifera) of the variation in composition. In general, satellite-derived parameters outperformed locally measured parameters. PMID- 27179998 TI - Molecular phylogeny and community fingerprinting of coral-associated Symbiodinium north of the Arabian Gulf. AB - Understanding coral-Symbiodinium relationships including changes in the genotypes and the numbers of Symbiodinium can explain the ability of Kuwait coral to survive high fluctuations in water temperature. In the current study, the diversity of Symbiodinium associated with fourteen coral species from six reef systems south of Kuwait was investigated. The results proved the predominance of clade C members in all corals tested, which reflects the importance of this type in helping corals thrive in the Gulf's harsh conditions. Platygyra daedalea was the only coral found that harbored clades A, B and C in their tissue but it is the most vulnerable coral for bleaching. The total number of Symbiodinium-like cells in the seawater was 10(4) cell ml(-1) while in coral tissue and mucus 10(7) cell g(-1) and 10(7) cell ml(-1) were found, respectively, and a strong positive correlation with the seawater temperature, salinity and conductivity was found. PMID- 27179999 TI - A double-blind, placebo-controlled, crossover trial of the selective dopamine D1 receptor antagonist ecopipam in patients with Lesch-Nyhan disease. AB - Lesch-Nyhan disease (LND) is a genetic disorder that has characteristic metabolic, neurologic, and behavioral features. There are multiple behavioral problems including impulsivity, aggressiveness, and severe recurrent self injurious behavior (SIB). This last behavior varies considerably across subjects and may encompass self-biting, self-hitting, scratching, head banging, and other injurious actions. Current treatments for SIB involve behavioral extinction, sedatives, physical restraints, and removal of teeth. Because these interventions do not reliably control SIB, better treatments are urgently needed. Animal studies have suggested that D1-dopamine receptor antagonists such as ecopipam may suppress SIB. These observations have led to proposals that such drugs might provide effective treatment for in LND. The current study describes the results of a double-blind, three-period, crossover trial of a single dose of ecopipam in subjects with LND. The study was designed for 20 patients, but it was terminated after recruitment of only 10 patients, because interim analysis revealed unanticipated side effects. These side effects were most likely related to starting with a single large dose without any titration phase. Despite the limited data due to early termination, the drug appeared to reduce SIB in most cases. Subjects who completed the trial were eligible to continue the drug in an open-label extension phase lasting a year, and one patient who elected to continue has maintained a striking reduction in SIB for more than a year with no apparent side effects. These results suggest ecopipam could be a useful treatment for SIB in, but further studies are needed to establish an appropriate dosing regimen. PMID- 27180001 TI - The role of the retino-colliculo-extrastriate pathway in visual awareness and visual field recovery. AB - Patients with visual field defects resulting from post-chiasmatic lesions experience loss of visual function in up to one half of their visual field, with consequent impairments in their daily life activities. Therefore, effective strategies for compensating for the visual field loss are of great clinical relevance. After lesions to the primary visual pathway -which conveys visual information from the retina to the lateral geniculate nucleus, the optic radiations and, then, to the striate cortex-an alternative visual pathway, which projects from the superior colliculus to the extrastriate cortex, is usually spared in patients with visual field defects. In the present review, evidence for spared functioning of this alternative pathway in patients with visual field defects will be presented, both in terms of residual visual abilities, without awareness, for stimuli presented in the blind field, and the ability to integrate unseen visual signals presented in the blind field with concurrent auditory stimuli. Crucially, this review will discuss how the spared retino-colliculo extrastriate pathway might be a useful tool for compensating for the loss of visual perception. Accordingly, evidence for the compensatory effects of systematic multisensory audio-visual stimulation in patients with visual field defects will be reviewed. PMID- 27180000 TI - Signal functions for measuring the ability of health facilities to provide abortion services: an illustrative analysis using a health facility census in Zambia. AB - BACKGROUND: Annually, around 44 million abortions are induced worldwide. Safe termination of pregnancy (TOP) services can reduce maternal mortality, but induced abortion is illegal or severely restricted in many countries. All abortions, particularly unsafe induced abortions, may require post-abortion care (PAC) services to treat complications and prevent future unwanted pregnancy. We used a signal-function approach to look at abortion care services and illustrated its utility with secondary data from Zambia. METHODS: We refined signal functions for basic and comprehensive TOP and PAC services, including family planning (FP), and assessed functions currently being collected via multi-country facility surveys. We then used the 2005 Zambian Health Facility Census to estimate the proportion of 1369 health facilities that could provide TOP and PAC services under three scenarios. We linked facility and population data, and calculated the proportion of the Zambian population within reach of such services. RESULTS: Relevant signal functions are already collected in five facility assessment tools. In Zambia, 30 % of facilities could potentially offer basic TOP services, 3.7 % comprehensive TOP services, 2.6 % basic PAC services, and 0.3 % comprehensive PAC services (four facilities). Capability was highest in hospitals, except for FP functions. Nearly two-thirds of Zambians lived within 15 km of a facility theoretically capable of providing basic TOP, and one-third within 15 km of comprehensive TOP services. However, requiring three doctors for non-emergency TOP, as per Zambian law, reduced potential access to TOP services to 30 % of the population. One-quarter lived within 15 km of basic PAC and 13 % of comprehensive PAC services. In a scenario not requiring FP functions, one-half and one-third of the population were within reach of basic and comprehensive PAC respectively. There were huge urban-rural disparities in access to abortion care services. Comprehensive PAC services were virtually unavailable to the rural population. CONCLUSIONS: Secondary data from facility assessments can highlight gaps in abortion service provision and coverage, but it is necessary to consider TOP and PAC separately. This approach, especially when combined with population data using geographic coordinates, can also be used to model the impact of various policy scenarios on access, such as requiring three medical doctors for non-emergency TOP. Data collection instruments could be improved with minor modifications and used for multi-country comparisons. PMID- 27180002 TI - Distinct preference for spatial frequency content in ventral stream regions underlying the recognition of scenes, faces, bodies and other objects. AB - The ventral visual pathway receives both inputs from parvocellular and magnocellular pathways, and combines information from distinct high and low spatial frequency channels (HSF and LSF). Using a random effects region of interest general linear model approach (n=21), we aimed to compare the selectivity to different spatial frequency channels in eight key areas involved in visual object recognition: FFA, OFA, and STS, for face processing; FBA, and EBA as body selective regions; (dorsal and ventral) LOC for object perception; PPA for processing information of places and VWFA as a region which responds to written verbal material. We found that face and body selective regions had significantly higher response to LSF, suggesting an important contribution of holistic processing favoring LSF channels, while other object responsive regions had a higher response to HSF, suggesting a more important role for detailed component processing. Both FBA and VWFA failed to reveal a preference to SF content. These findings apply in general to the preferred category, with the notable exception of PPA, which revealed a higher response to HSF for all categories of stimuli. Our results suggest that areas along the ventral stream have distinct spatial frequency preferences that seem to reflect both the nature of visual objects being processed, their position in the visual hierarchy, task demands and the relevance of holistic versus detailed processing. PMID- 27180003 TI - Extrafacial Lentigo Maligna: A Report on 14 Cases and a Review of the Literature. AB - Lentigo maligna is the most common form of in situ melanoma. It is most often found on the head and neck, and its clinical and dermoscopic features in this location have been extensively described in the literature. We present a series of 14 patients diagnosed with extrafacial lentigo maligna and lentigo maligna melanoma at Hospital General de Valencia and Hospital de Manacor in Spain, and describe the clinical, dermoscopic, and histologic features observed. Most of the melanomas were located on the upper limbs; the next most common locations were the trunk and the lower limbs. The dermoscopic patterns were consistent with facial lentigo maligna and superficial spreading melanoma. Extrafacial lentigo maligna is uncommon. It has similar clinical and histologic features to facial lentigo, but dermoscopy may show a mix of patterns typically seen in lentigo maligna and superficial spreading melanoma. This difference in dermoscopic features is essentially due to anatomical differences between skin on the face and on other parts of the body. PMID- 27180004 TI - The Spanish Standard Patch Test Series. PMID- 27180005 TI - A rare case of SPG11 mutation with multiple sclerosis. AB - We describe a patient with SPG11 hereditary spastic paraplegia (HSP), who developed walking disorder in childhood. He presented three episodes of subacute gait disorders worsening between the age of 20 and 22 years. Brain and spinal MRI revealed multiple T2 hypersignal lesions, consistent with inflammatory lesions. Surprisingly, CSF analysis showed neither oligoclonal bands nor increased IgG index. He was dramatically improved by intravenous methylprednisolone. A relapsing-remitting multiple sclerosis (MS) was suspected. This is the first description of SPG11 HSP associated with MS. PMID- 27180007 TI - Administration of probiotic kefir to mice with Clostridium difficile infection exacerbates disease. AB - Lifeway((r)) kefir, a fermented milk product containing 12 probiotic organisms, is reported to show promise as an alternative to fecal microbiota transplantation for recurrent Clostridium difficile infection (CDI). We employed a murine CDI model to study the probiotic protective mechanisms and unexpectedly determined that kefir drastically increased disease severity. Our results emphasize the need for further independent clinical testing of kefir as alternative therapy in recurrent CDI. PMID- 27180006 TI - Structural and functional changes within the gut microbiota and susceptibility to Clostridium difficile infection. AB - Alteration of the gut microbial community structure and function through antibiotic use increases susceptibility to colonization by Clostridium difficile and other enteric pathogens. However, the mechanisms that mediate colonization resistance remain elusive. As the leading definable cause of infectious diarrhea, toxigenic C. difficile represents a burden for patients and health care systems, underscoring the need for better diagnostics and treatment strategies. Next generation sequence data has increased our understanding of how the gut microbiota is influenced by many factors including diet, disease, aging and drugs. However, a microbial-based biomarker differentiating C. difficile infection from antibiotic-associated diarrhea has not been identified. Metabolomics profiling, which is highly responsive to changes in physiological conditions, have shown promise in differentiating subtle disease phenotypes that exhibit a nearly identical microbiome community structure, suggesting metabolite based biomarkers may be an ideal diagnostic for identifying patients with CDI. This review focuses on the current understanding of structural and functional changes to the gut microbiota during C. difficile infection obtained from studies assessing the microbiome and metabolome of samples from patients and murine models. PMID- 27180009 TI - Verapamil and ethacrynic acid are associated with neuronal acidification in hippocampal CA3-neurons (slice preparation, guinea pig): Contribution to their anti-seizure potency? PMID- 27180008 TI - The expanding GRK interactome: Implications in cardiovascular disease and potential for therapeutic development. AB - Heart failure (HF) is a global epidemic with the highest degree of mortality and morbidity of any disease presently studied. G protein-coupled receptors (GPCRs) are prominent regulators of cardiovascular function. Activated GPCRs are "turned off" by GPCR kinases (GRKs) in a process known as "desensitization". GRKs 2 and 5 are highly expressed in the heart, and known to be upregulated in HF. Over the last 20 years, both GRK2 and GRK5 have been demonstrated to be critical mediators of the molecular alterations that occur in the failing heart. In the present review, we will highlight recent findings that further characterize "non canonical" GRK signaling observed in HF. Further, we will also present potential therapeutic strategies (i.e. small molecule inhibition, microRNAs, gene therapy) that may have potential in combating the deleterious effects of GRKs in HF. PMID- 27180011 TI - Estimating genotype and allele frequencies of the CYP2D6 gene. PMID- 27180010 TI - Segetoside I, a plant-derived bisdesmosidic saponin, induces apoptosis in human hepatoma cells in vitro and inhibits tumor growth in vivo. AB - Segetoside I is a plant-derived bisdesmosidic saponin from Vaccaria segetalis (Neck) with reported anticancer activities. This development has raised an interest in the therapeutic potential of segetoside I. Here, we report the in vitro and in vivo antitumor activities of segetoside I against some selected cancer cell lines (HepG2, human hepatoma; H22, mouse hepatoma; MCF-7, breast cancer; U251, gliocoma; BGC, HGC & SGC, gastric cancinoma; Lovo-1,colon cancer). MTT bioassay analysis showed that HepG2 cells were the most sensitive to segetoside I compared with other cancer cell lines, with lower toxicity in healthy mouse embryonic fibroblast cells. Segetoside I pretreatment of HepG2 resulted in apoptotic induction, dose-dependent DNA fragmentation, inhibition of cell migration, up-regulation of Bax and down-regulation of Bcl-2, which indicated that an apoptotic signaling event could have been initiated. The segetoside I also suppressed hepato-tumour growth in mice with virtually no cytotoxicity and prolonged animal survival, making it a strong oncology drug agent. These findings showed that segetoside I exhibited its antitumor activity via apoptotic induction and significantly support the possible application of the antitumor agent as a potential chemotherapeutic candidate worthy of further investigations. PMID- 27180012 TI - Synthesis and evaluation of novel benzylphthalazine derivatives as hedgehog signaling pathway inhibitors. AB - We report herein the design and synthesis of a series of novel benzylphthalazine derivatives as hedgehog signaling pathway inhibitors. Gli-luciferase assay demonstrated that changing piperazine ring of Anta XV to different four, five or six-membered heterocyclic building blocks afforded significant influences on Hh pathway inhibition. In particular, compound 10e with piperidin-4-amine moiety was found to possess 12-fold higher Hh inhibitory activities comparing to the lead compound in vitro. In vivo efficacy of 10e in a ptch(+/-)p53(-/-) mouse medulloblastoma allograft model also indicated encouraging results. PMID- 27180014 TI - Corrigendum to "Reduced intrasubject variability with reinforcement in boys, but not girls, with ADHD: Associations with prefrontal anatomy" [Biol. Psychol. 110 (2015) 12-23]. PMID- 27180013 TI - Discovery of fused tricyclic core containing HCV NS5A inhibitors with pan genotype activity. AB - HCV NS5A inhibitors have demonstrated impressive in vitro potency profiles in HCV replicon assays and robust HCV RNA titer reduction in the clinic making them attractive components for inclusion in an all oral fixed dose combination regimen for the treatment of HCV infection. Herein, we describe research efforts that led to the discovery of a series of fused tricyclic core containing HCV NS5A inhibitors such as 24, 39, 40, 43, and 44 which have pan-genotype activity and are orally bioavailable in the rat. PMID- 27180015 TI - Corrigendum to "Upward spirals of the heart: Autonomic flexibility, as indexed by vagal tone, reciprocally and prospectively predicts positive emotions and social connectedness" [Biol. Psychol. 85 (3) (2010) 432-436]. PMID- 27180016 TI - Adapting to adolescence. PMID- 27180017 TI - Smoking and mental health. PMID- 27180018 TI - The nasal microbiota in infants with cystic fibrosis in the first year of life: a prospective cohort study. AB - BACKGROUND: Respiratory tract infections and subsequent airway inflammation occur early in the life of infants with cystic fibrosis. However, detailed information about the microbial composition of the respiratory tract in infants with this disorder is scarce. We aimed to undertake longitudinal in-depth characterisation of the upper respiratory tract microbiota in infants with cystic fibrosis during the first year of life. METHODS: We did this prospective cohort study at seven cystic fibrosis centres in Switzerland. Between Feb 1, 2011, and May 31, 2014, we enrolled 30 infants with a diagnosis of cystic fibrosis. Microbiota characterisation was done with 16S rRNA gene pyrosequencing and oligotyping of nasal swabs collected every 2 weeks from the infants with cystic fibrosis. We compared these data with data for an age-matched cohort of 47 healthy infants. We additionally investigated the effect of antibiotic treatment on the microbiota of infants with cystic fibrosis. Statistical methods included regression analyses with a multivariable multilevel linear model with random effects to correct for clustering on the individual level. FINDINGS: We analysed 461 nasal swabs taken from the infants with cystic fibrosis; the cohort of healthy infants comprised 872 samples. The microbiota of infants with cystic fibrosis differed compositionally from that of healthy infants (p=0.001). This difference was also found in exclusively antibiotic-naive samples (p=0.001). The disordering was mainly, but not solely, due to an overall increase in the mean relative abundance of Staphylococcaceae in infants with cystic fibrosis compared with healthy infants (multivariable linear regression model stratified by age and adjusted for season; second month: coefficient 16.2 [95% CI 0.6-31.9]; p=0.04; third month: 17.9 [3.3-32.5]; p=0.02; fourth month: 21.1 [7.8-34.3]; p=0.002). Oligotyping analysis enabled differentiation between Staphylococcus aureus and coagulase negative Staphylococci. Whereas the analysis showed a decrease in S aureus at and after antibiotic treatment, coagulase-negative Staphylococci increased. INTERPRETATION: Our study describes compositional differences in the microbiota of infants with cystic fibrosis compared with healthy controls, and disordering of the microbiota on antibiotic administration. Besides S aureus, coagulase negative Staphylococci also contributed to the disordering identified in these infants. These findings are clinically important in view of the crucial role that bacterial pathogens have in the disease progression of cystic fibrosis in early life. Our findings could be used to inform future studies of the effect of antibiotic treatment on the microbiota in infants with cystic fibrosis, and could assist in the prevention of early disease progression in infants with this disorder. FUNDING: Swiss National Science Foundation, Fondation Botnar, the Swiss Society for Cystic Fibrosis, and the Swiss Lung Association Bern. PMID- 27180019 TI - Experts recognise zoonotic TB. PMID- 27180020 TI - Multidisciplinary discussions and interstitial lung disease diagnosis: how useful is a meeting of the minds? PMID- 27180023 TI - Comparison of the Effect of Electrical Stimulations on the Chin Skin on Autonomic Nervous Activities During Propofol Sedation With or Without Midazolam. AB - PURPOSE: The aim of this study was to compare the effect of electrical stimulations on the chin skin on autonomic nervous activities evaluated by use of power spectrum analysis of heart rate (HR) variability during intravenous sedation using propofol with or without midazolam. MATERIALS AND METHODS: Thirty eight healthy adult male volunteers underwent intravenous sedation with midazolam and propofol (group MP) and with propofol alone (group P) in a randomized crossover manner. In group MP, the participants received midazolam (0.04 mg/kg) and a target-controlled infusion of propofol with a predicted blood concentration of 1.0 MUg/mL. In group P, the predicted blood concentration of propofol was maintained at 1.5 MUg/mL. The observed variables were bispectral index value, systolic blood pressure, HR, high-frequency component (HF), low-frequency component (LF), and LF/HF ratio. Measurements were conducted over 100-second periods and carried out before, during, and after emergence from sedation by administering 0.2 mg of flumazenil. The paired t test, Wilcoxon t test, repeated measures analysis of variance, and Friedman chi(2) r test were used for statistical analyses. RESULTS: The mean age and body weight of the participants were 24.6 +/- 2.8 years and 67.0 +/- 7.9 kg, respectively. Bispectral index values, systolic blood pressure, and HR showed similar changes in both groups. The LF/HF ratio in group MP during sedation was lower than that before sedation; it also was lower than that in group P during sedation. CONCLUSIONS: Intravenous sedation with a combination of midazolam and propofol inhibited sympathetic nervous activation induced by electrical stimulations to a greater extent than that with propofol alone. PMID- 27180022 TI - Current and future trends in the lipid lowering therapy. AB - Atherosclerosis is an inflammatory disease that affects arterial wall. It leads to wall thickening and its instability. As a result a reduction in lumen diameter and blood flow is observed. This manifests predominantly as the affectation of vascular bed of coronary (myocardial infarction), cerebral, carotid (ischemic stroke) or peripheral arteries (limb amputation). One of the most important factors that accelerate atherosclerosis is hyperlipidemia. According to current guidelines the main attention should be focused on the treatment of hyperlipidemia (beside the prevention, which includes proper diet, physical activity and risk factors avoidance). Major attention is given to LDL (low density lipoprotein) cholesterol (LDL-C) level as primary, and triglyceride level as secondary targets of therapy. As a result of recent clinical findings and continuous research in the field of hypolipidemic drugs it seems practical to review recent data and show potential new pathways that may be useful in the treatment of hyperlipidemia. The review is divided into several parts presenting the widely used and well-known hypolipidemic drugs. In the first part a brief review of contemporary drugs affecting LDL cholesterol is shown. The second part contains information regarding currently available drugs reducing triglycerides level. The third part describes several novel and promising groups of drugs that are still on various steps of clinical development. In the last part drugs affecting HDL (high-density lipoprotein) level were presented. PMID- 27180024 TI - Prevalence and characterization of plasmid-mediated quinolone resistance genes in Aeromonas spp. isolated from South African freshwater fish. AB - An increasing incidence of multidrug-resistant Aeromonas spp., which are both fish and emerging opportunistic human pathogens, has been observed worldwide. Quinolone-resistant Aeromonas spp. isolates are increasingly being observed in clinical and environmental settings, and this has been attributed primarily to target gene alterations, efflux, and transferable quinolone resistance. Thirty four Aeromonas spp., obtained from freshwater aquaculture systems, were screened for the presence of GyrA and ParC substitutions, efflux activity and the prevalence of plasmid-mediated quinolone resistance genes, qnr and aac-6'-Ib-cr. Although 44% of isolates were resistant to nalidixic acid, the majority were susceptible to ciprofloxacin and ofloxacin. The predominant GyrA substitution was Ser-83->Val among Aeromonas veronii isolates whilst Aeromonas hydrophila isolates displayed a Ser-83->Ile substitution, and Ser-80->Ile substitutions were observed in ParC. Minimum inhibitory concentrations of fluoro(quinolones) were determined in the presence and absence of the efflux pump inhibitor, phenylalanine-arginine beta-naphthylamide (PAbetaN). Addition of PAbetaN had no effect on the levels of fluoro(quinolone) resistance observed for these isolates. Although no aac-6'-Ib cr variant genes were identified, qnrB and qnrS were detected for 41% and 24% of isolates, respectively, by Southern hybridization and confirmed by PCR and sequencing. Quinolone resistance in these fish-associated Aeromonas isolates was related to mutations in the quinolone resistance determining regions of GyrA and ParC and presence of qnrB and qnrS. The presence of qnr alleles in Aeromonas spp. isolates may facilitate high-level fluoroquinolone resistance and potentially serve as reservoirs for the dissemination of qnr genes to other aquatic microbes. PMID- 27180021 TI - Multicentre evaluation of multidisciplinary team meeting agreement on diagnosis in diffuse parenchymal lung disease: a case-cohort study. AB - BACKGROUND: Diffuse parenchymal lung disease represents a diverse and challenging group of pulmonary disorders. A consistent diagnostic approach to diffuse parenchymal lung disease is crucial if clinical trial data are to be applied to individual patients. We aimed to evaluate inter-multidisciplinary team agreement for the diagnosis of diffuse parenchymal lung disease. METHODS: We did a multicentre evaluation of clinical data of patients who presented to the interstitial lung disease unit of the Royal Brompton and Harefield NHS Foundation Trust (London, UK; host institution) and required multidisciplinary team meeting (MDTM) characterisation between March 1, 2010, and Aug 31, 2010. Only patients whose baseline clinical, radiological, and, if biopsy was taken, pathological data were undertaken at the host institution were included. Seven MDTMs, consisting of at least one clinician, radiologist, and pathologist, from seven countries (Denmark, France, Italy, Japan, Netherlands, Portugal, and the UK) evaluated cases of diffuse parenchymal lung disease in a two-stage process between Jan 1, and Oct 15, 2015. First, the clinician, radiologist, and pathologist (if lung biopsy was completed) independently evaluated each case, selected up to five differential diagnoses from a choice of diffuse lung diseases, and chose likelihoods (censored at 5% and summing to 100% in each case) for each of their differential diagnoses, without inter-disciplinary consultation. Second, these specialists convened at an MDTM and reviewed all data, selected up to five differential diagnoses, and chose diagnosis likelihoods. We compared inter-observer and inter-MDTM agreements on patient first-choice diagnoses using Cohen's kappa coefficient (kappa). We then estimated inter-observer and inter-MDTM agreement on the probability of diagnosis using weighted kappa coefficient (kappaw). We compared inter-observer and inter-MDTM confidence of patient first-choice diagnosis. Finally, we evaluated the prognostic significance of a first-choice diagnosis of idiopathic pulmonary fibrosis (IPF) versus not IPF for MDTMs, clinicians, and radiologists, using univariate Cox regression analysis. FINDINGS: 70 patients were included in the final study cohort. Clinicians, radiologists, pathologists, and the MDTMs assigned their patient diagnoses between Jan 1, and Oct 15, 2015. IPF made up 88 (18%) of all 490 MDTM first-choice diagnoses. Inter-MDTM agreement for first choice diagnoses overall was moderate (kappa=0.50). Inter-MDTM agreement on diagnostic likelihoods was good for IPF (kappaw=0.71 [IQR 0.64-0.77]) and connective tissue disease-related interstitial lung disease (kappaw=0.73 [0.68 0.78]); moderate for non-specific interstitial pneumonia (NSIP; kappaw=0.42 [0.37 0.49]); and fair for hypersensitivity pneumonitis (kappaw=0.29 [0.24-0.40]). High confidence diagnoses (>65% likelihood) of IPF were given in 68 (77%) of 88 cases by MDTMs, 62 (65%) of 96 cases by clinicians, and in 57 (66%) of 86 cases by radiologists. Greater prognostic separation was shown for an MDTM diagnosis of IPF than compared with individual clinician's diagnosis of this disease in five of seven MDTMs, and radiologist's diagnosis of IPF in four of seven MDTMs. INTERPRETATION: Agreement between MDTMs for diagnosis in diffuse lung disease is acceptable and good for a diagnosis of IPF, as validated by the non-significant greater prognostic separation of an IPF diagnosis made by MDTMs than the separation of a diagnosis made by individual clinicians or radiologists. Furthermore, MDTMs made the diagnosis of IPF with higher confidence and more frequently than did clinicians or radiologists. This difference is of particular importance, because accurate and consistent diagnoses of IPF are needed if clinical outcomes are to be optimised. Inter-multidisciplinary team agreement for a diagnosis of hypersensitivity pneumonitis is low, highlighting an urgent need for standardised diagnostic guidelines for this disease. FUNDING: National Institute of Health Research, Imperial College London. PMID- 27180025 TI - Data-based fault-tolerant control for affine nonlinear systems with actuator faults. AB - This paper investigates the fault-tolerant control (FTC) problem for unknown nonlinear systems with actuator faults including stuck, outage, bias and loss of effectiveness. The upper bounds of stuck faults, bias faults and loss of effectiveness faults are unknown. A new data-based FTC scheme is proposed. It consists of the online estimations of the bounds and a state-dependent function. The estimations are adjusted online to compensate automatically the actuator faults. The state-dependent function solved by using real system data helps to stabilize the system. Furthermore, all signals in the resulting closed-loop system are uniformly bounded and the states converge asymptotically to zero. Compared with the existing results, the proposed approach is data-based. Finally, two simulation examples are provided to show the effectiveness of the proposed approach. PMID- 27180027 TI - Macronutrient Composition of Menu Offerings in Fast Food Restaurants in the U.S. AB - INTRODUCTION: A high intake of fast food is associated with increased obesity risk. This study assessed recent changes in caloric content and macronutrient composition in large U.S. fast food restaurants. METHODS: Data from the MenuStat project included 11,737 menu items in 37 fast food restaurants from 2012 to 2014. Generalized linear models were used to examine changes in the caloric content and corresponding changes in the macronutrient composition (non-sugar carbohydrates, sugar, unsaturated fat, saturated fat, and protein) of menu items over time. Additionally, macronutrient composition was compared in menu items newly introduced in 2013 and 2014, relative to 2012. Analyses, conducted in January 2016, controlled for restaurant and were stratified by menu categories. RESULTS: Overall, there was a 22-calorie reduction in food items from 2012 to 2014. Beverages had a 46-calorie increase, explained by an increase in calories from sugar (12 calories) and saturated fat (16 calories). Newly introduced main courses in 2014 had 59 calories fewer than those on 2012 menus, explained by a 54 calorie reduction in unsaturated fat, while other macronutrient content remained fairly constant. Newly introduced dessert items in 2014 had 90 calories more than those on 2012 menus, explained primarily by an increase of 57 calories of sugar. CONCLUSIONS: Overall, there were relatively minor changes in menu items' caloric and macronutrient composition. Although declines in caloric content among newly introduced fast food main courses may improve the public's caloric intake, it appears that the macronutrient composition of newly introduced items did not shift to a healthier profile. PMID- 27180026 TI - Nondestructive evaluation of a new hydrolytically degradable and photo-clickable PEG hydrogel for cartilage tissue engineering. AB - Photopolymerizable and hydrolytically labile poly(ethylene glycol) (PEG) hydrogels formed from photo-clickable reactions were investigated as cell delivery platforms for cartilage tissue engineering (TE). PEG hydrogels were formed from thiol-norbornene PEG macromers whereby the crosslinks contained caprolactone segments with hydrolytically labile ester linkages. Juvenile bovine chondrocytes encapsulated in the hydrogels were cultured for up to four weeks and assessed biochemically and histologically, using standard destructive assays, and for mechanical and ultrasound properties, as nondestructive assays. Bulk degradation of acellular hydrogels was confirmed by a decrease in compressive modulus and an increase in mass swelling ratio over time. Chondrocytes deposited increasing amounts of sulfated glycosaminoglycans and collagens in the hydrogels with time. Spatially, collagen type II and aggrecan were present in the neotissue with formation of a territorial matrix beginning at day 21. Nondestructive measurements revealed an 8-fold increase in compressive modulus from days 7 to 28, which correlated with total collagen content. Ultrasound measurements revealed changes in the constructs over time, which differed from the mechanical properties, and appeared to correlate with ECM structure and organization shown by immunohistochemical analysis. Overall, non-destructive and destructive measurements show that this new hydrolytically degradable PEG hydrogel is promising for cartilage TE. STATEMENT OF SIGNIFICANCE: Designing synthetic hydrogels whose degradation matches tissue growth is critical to maintaining mechanical integrity as the hydrogel degrades and new tissue forms, but is challenging due to the nature of the hydrogel crosslinks that inhibit diffusion of tissue matrix molecules. This study details a promising, new, photo-clickable and synthetic hydrogel whose degradation supports cartilaginous tissue matrix growth leading to the formation of a territorial matrix, concomitant with an increase in mechanical properties. Nondestructive assays based on mechanical and ultrasonic properties were also investigated using a novel instrument and found to correlate with matrix deposition and evolution. In sum, this study presents a new hydrogel platform combined with nondestructive assessments, which together have potential for in vitro cartilage tissue engineering. PMID- 27180028 TI - Predictors of the Onset of Cigarette Smoking: A Systematic Review of Longitudinal Population-Based Studies in Youth. AB - CONTEXT: The onset of cigarette smoking typically occurs during childhood or early adolescence. Nicotine dependence symptoms can manifest soon after onset, contributing to sustained, long-term smoking. Previous reviews have not clarified the determinants of onset. EVIDENCE ACQUISITION: In 2015, a systematic review of the literature in PubMed and EMBASE was undertaken to identify peer-reviewed prospective longitudinal studies published between January 1984 and August 2015 that investigated predictors of cigarette smoking onset among youth aged <18 years who had never smoked. EVIDENCE SYNTHESIS: Ninety-eight conceptually different potential predictors were identified in 53 studies. An increased risk of smoking onset was consistently (i.e., in four or more studies) associated with increased age/grade, lower SES, poor academic performance, sensation seeking or rebelliousness, intention to smoke in the future, receptivity to tobacco promotion efforts, susceptibility to smoking, family members' smoking, having friends who smoke, and exposure to films, whereas higher self-esteem and high parental monitoring/supervision of the child appeared to protect against smoking onset. Methodologic weaknesses were identified in numerous studies, including failure to account for attrition or for clustering in samples, and misidentification of potential confounders, which may have led to biased estimates of associations. CONCLUSIONS: Predictors of smoking onset for which there is robust evidence should be considered in the design of interventions to prevent first puff in order to optimize their effectiveness. Future research should seek to define onset clearly as the transition from never use to first use (e.g., first few puffs). PMID- 27180029 TI - Perceived Neighborhood Environment and Physical Activity: The International Physical Activity and Environment Network Adult Study in Mexico. AB - INTRODUCTION: There is compelling evidence linking physical activity with environmental characteristics in high-income countries, but evidence among low- and middle-income countries is scarce and results are inconsistent. This study assessed associations between perceived measures of the built environment and objectively measured physical activity among Mexican adults. METHODS: A population-based study of adults aged 20-65 years was conducted in Cuernavaca, Mexico, in 2011 (N=629). Participants wore an accelerometer for 7 days. Perceived environment data were obtained by questionnaire. In 2014, multiple regression models estimated the association between perceived environmental variables and total moderate to vigorous physical activity (MVPA); MVPA within 10-minute bouts was analyzed using a two-part model. RESULTS: Easy access to neighborhood parks and close proximity to metropolitan parks were positively associated with total MVPA. Proximity to metropolitan parks was also positively related to any MVPA within bouts among women. High perceived aesthetics among those of low SES and high perceived safety from crime among men were positively associated with total MVPA and MVPA within bouts. Having few cul-de-sacs within the neighborhood and proximity to transit stops were inversely related to total MVPA. CONCLUSIONS: Access to parks, aesthetics, and safety from crime are important correlates of physical activity among Mexican adults. Yet, this study finds no association for other environmental features usually thought to be important for increasing activity levels. These findings highlight the importance of conducting more studies in low- and middle-income countries that examine the relationship between physical activity and the built environment. PMID- 27180030 TI - Effects of Child Care Intervention on Physical Activity and Body Composition. AB - INTRODUCTION: This study evaluated whether intervening with child care providers would increase physical activity (PA) and reduce adiposity in preschoolers. METHODS: This was a two-arm, parallel group, cluster RCT whereby six child care centers were randomly assigned in equal numbers to intervention (n=40 children) or control (n=43 children). Participants were aged 3-5 years and attended licensed child care centers. Child care providers received two 3-hour train-the trainer workshops and a training manual at program initiation aimed at increasing structured and unstructured PA through active play. Control child care centers implemented their standard curriculum. PA and sedentary behavior were measured by accelerometry, and body composition was measured using bioelectrical impedance at baseline and 6 months. Data were collected in 2011-2012 and analyzed in April 2015. RESULTS: Linear mixed-effects modeling showed that at 6 months, children in the intervention group demonstrated greater increases in minutes per preschool day spent in overall PA (22.5 minutes, 95% CI=8.9, 36.1, p=0.002), and light intensity PA (16.1 minutes, 95% CI=5.2, 26.7, p=0.004), but changes between groups in moderate to vigorous PA did not differ. The intervention group showed greater reductions in body fat percentage (-1.9%, 95% CI=-3.5, -0.3, p=0.023) and fat mass (-0.3 kg, 95% CI=-0.7, -0.1, p=0.018), but groups did not differ on fat free mass, BMI, or z-BMI. CONCLUSIONS: Provider-led intervention in child care centers increased preschoolers' PA and reduced adiposity, therefore may represent a viable approach to promoting PA and related health benefits in preschool-aged children. TRIAL REGISTRATION: This study is registered at www.clinicaltrials.gov NCT02293278. PMID- 27180031 TI - Combined Impact of Health Behaviors on Mortality in Low-Income Americans. AB - INTRODUCTION: African Americans and low-income whites have higher mortality than the U.S. general population. This study prospectively investigated the combined influence of major lifestyle factors and poverty on mortality in this vulnerable population. METHODS: Data were collected in 2002-2009 from 79,101 Southern Community Cohort Study participants, of which 67% were African American and 55% had household incomes <$15,000. Mortality outcomes were identified from the National Death Index though December 31, 2011 (data analyzed in 2014-2015). Healthy behavior scores were created based on tobacco smoking, alcohol intake, diet, physical activity, and sedentary time. The primary analysis was performed based on the score created by counting each participant as having met/not met public health guidelines for each behavior. RESULTS: Healthy behavior scores were associated with reduced cancer, cardiovascular disease, and all-cause mortality. Associations were stronger for whites than African Americans: hazard ratios for all-cause mortality comparing participants meeting four or five guidelines versus participants meeting zero were 0.41 (95% CI=0.30, 0.55) for African American men; 0.36 (95% CI=0.24, 0.55) for white men; 0.46 (95% CI=0.36, 0.59) for African American women; and 0.27 (95% CI=0.18, 0.43) for white women. The association between healthy lifestyle and all-cause mortality was weaker among those with incomes <$15,000 than those with higher income, particularly in men (p<0.05 for interaction). CONCLUSIONS: This study demonstrates the importance of health behaviors on mortality among all groups, but highlights the need for additional research to identify factors contributing to high risk of mortality among low income and African American populations. PMID- 27180032 TI - In pursuit of academic plastic surgery training: The O'Brien experience. PMID- 27180033 TI - Neuroprotection in acute stroke: targeting excitotoxicity, oxidative and nitrosative stress, and inflammation. AB - Treatments for acute ischaemic stroke continue to evolve after the superior value of endovascular thrombectomy was confirmed over systemic thrombolysis. Unfortunately, numerous neuroprotective drugs have failed to show benefit in the treatment of acute ischaemic stroke, making the search for new treatments imperative. Increased awareness of the relevance of rigorous preclinical testing, and appropriate selection of study participants, might overcome the barriers to progress in stroke research. Relevant areas of interest include the search for safe and effective treatment strategies that combine neuroprotection reperfusion, better use of advanced brain imaging for patient selection, and wider implementation of prehospital conducted clinical trials. Randomised controlled trials of combination treatments completed within the past 5 years have included growth factors, hypothermia, minocycline, natalizumab, fingolimod, and uric acid; the latter two drugs with alteplase produced encouraging results. Blocking of excitotoxicity is also being reassessed in clinical trials with new approaches, such as the postsynaptic density-95 inhibitor NA-1, or peritoneal dialysis to remove excess glutamate. The findings of these randomised trials are anticipated to improve treatment options and clinical outcomes in of patients with acute stroke. PMID- 27180035 TI - Goal conceptualization and symmetry of arm movements affect bimanual coordination in individuals after stroke. AB - Coordination during goal-directed movements emerges from an interaction of task and individual constraints. It is not known how individuals with unilateral stroke and age-matched controls coordinate their arms when performing symmetric and asymmetric movements to accomplish common task goals compared to independent task goals. Eleven individuals with chronic stroke and ten age-matched controls executed a bimanual task under virtual conditions that allowed systematic manipulation of symmetry and goal conditions. Spatial and temporal bimanual coordination was characterized using the cross-correlation coefficients and time lag between the tangential velocities between the two hands. While task conditions had little effect on coordination of control participants, individuals with stroke were less coordinated in space and time during common-goal bimanual actions employing asymmetric arm movements. Further, patients demonstrated lesser contribution of their paretic arm compared to their non-paretic arm during common goal conditions. These findings indicate that conceptualization of task goals (common vs. independent) and symmetry of arm movements influence coordination and contribution of the two hands during bimanual tasks in patients with stroke. PMID- 27180034 TI - Cortical atrophy in patients with cerebral amyloid angiopathy: a case-control study. AB - BACKGROUND: Loss of cortical grey matter is a diagnostic marker of many neurodegenerative diseases, and is a key mediator of cognitive impairment. We postulated that cerebral amyloid angiopathy (CAA), characterised by cortical vascular amyloid deposits, is associated with cortical tissue loss independent of parenchymal Alzheimer's disease pathology. We tested this hypothesis in patients with hereditary cerebral haemorrhage with amyloidosis-Dutch type (HCHWA-D), a monogenetic disease with minimal or no concomitant Alzheimer's disease pathology, as well as in patients with sporadic CAA and healthy and Alzheimer's disease controls. METHODS: In this observational case-control study, we included six groups of participants: patients diagnosed with HCHWA-D using genetic testing; healthy controls age-matched to the HCHWA-D group; patients with probable sporadic CAA without dementia; two independent cohorts of healthy controls age matched to the CAA group; and patients with Alzheimer's disease age-matched to the CAA group. De-identified (but unmasked) demographic, clinical, radiological, and genetic data were collected at Massachusetts General Hospital (Boston, MA, USA), at Leiden University (Leiden, Netherlands), and at sites contributing to Alzheimer's Disease Neuroimaging Initiative (ADNI). The primary outcome measure was cortical thickness. The correlations between cortical thickness and structural lesions, and blood-oxygen-level-dependent time-to-peak (BOLD-TTP; a physiological measure of vascular dysfunction) were analysed to understand the potential mechanistic link between vascular amyloid and cortical thickness. The radiological variables of interest were quantified using previously validated computer-assisted tools, and all results were visually reviewed to ensure their accuracy. RESULTS: Between March 15, 2006, and Dec 1, 2014, we recruited 369 individuals (26 patients with HCHWA-D and 28 age-matched, healthy controls; 63 patients with sporadic CAA without dementia; two healthy control cohorts with 63 and 126 individuals; and 63 patients with Alzheimer's disease). The 26 patients with HCHWA-D had thinner cortices (2.31 mm [SD 0.18]) than the 28 healthy controls (mean difference -0.112 mm, 95% CI -0.190 to -0.034, p=0.006). The 63 patients with sporadic CAA without dementia had thinner cortices (2.17 mm [SD 0.11]) than the two healthy control cohorts (n=63, mean difference -0.14 mm, 95% CI -0.17 to -0.10, p<0.0001; and n=126, -0.10, -0.13 to -0.06, p<0.0001). All differences remained independent in multivariable analyses. The 63 patients with Alzheimer's disease displayed more severe atrophy than the patients with sporadic CAA (2.1 mm [SD 0.14], difference 0.07 mm, 95% CI 0.11 to 0.02, p=0.005). We found strong associations between cortical thickness and vascular dysfunction in the patients with HCHWA-D (rho=-0.58, p=0.003) or sporadic CAA (r=-0.4, p=0.015), but not in controls. Vascular dysfunction was identified as a mediator of the effect of hereditary CAA on cortical atrophy, accounting for 63% of the total effect. INTERPRETATION: The appearance of cortical thinning in patients with HCHWA-D indicates that vascular amyloid is an independent contributor to cortical atrophy. These results were reproduced in patients with the more common sporadic CAA. Our findings also suggest that CAA-related cortical atrophy is at least partly mediated by vascular dysfunction. Our results also support the view that small vessel diseases such as CAA can cause cortical atrophy even in the absence of Alzheimer's disease, a conclusion that can help radiologists, neurologists, and other clinicians who diagnose these common geriatric conditions. FUNDING: National Institutes of Health. PMID- 27180036 TI - Conversion from MCI to AD in patients with the APOE epsilon4 genotype: Prediction by plasma HCY and serum BDNF. AB - Amnestic mild cognitive impairment (aMCI) is a transitional stage between normal aging and Alzheimer's disease (AD). Possession of the apolipoprotein E (APOE) epsilon4 genotype is a major predictor of progression to AD, particularly in patients with aMCI. However, the use of APOE genotyping in the diagnosis of aMCI that evolves into AD is limited due to its low sensitivity and specificity. In this study, we found that there was a notable increase in plasma homocysteine (HCY) and significant decrease in serum brain-derived neurotrophic factor (BDNF) in aMCI that converts to AD in patients with the APOE epsilon4 allele. Both plasma HCY and serum BDNF had higher positive predictive values and were more sensitive biomarkers of aMCI. Additionally, a testing strategy employing plasma HCY and serum BDNF revealed increases in sensitivity, specificity, and predictive ability compared with the use of either biomarker alone. The present study demonstrates that MCI that evolves into AD in patients with the APOE epsilon4 genotype may be predicted by plasma HCY and serum BDNF. PMID- 27180037 TI - Photoreduction of the ferredoxin/ferredoxin-NADP(+)-reductase complex by a linked ruthenium polypyridyl chromophore. AB - Photosynthetic ferredoxin and its main partner ferredoxin-NADP(+)-reductase (FNR) are key proteins during the photoproduction of reductive power involved in photosynthetic growth. In this work, we used covalent attachment of ruthenium derivatives to different cysteine mutants of ferredoxin to trigger by laser-flash excitation both ferredoxin reduction and subsequent electron transfer from reduced ferredoxin to FNR. Rates and yields of reduction of the ferredoxin [2Fe 2S] cluster by reductively quenched Ru* could be measured for the first time for such a low redox potential protein whereas ferredoxin-FNR electron transfer was characterized in detail for one particular Ru-ferredoxin covalent adduct. For this adduct, the efficiency of FNR single reduction by reduced ferredoxin was close to 100% under both first-order and diffusion-limited second-order conditions. Interprotein intracomplex electron transfer was measured unambiguously for the first time with a fast rate of c. 6500s(-1). Our measurements point out that Ru photosensitizing is a powerful approach to study the functional interactions of ferredoxin with its numerous partners besides FNR. PMID- 27180038 TI - Comparison of electron microscopy, ELISA, real time RT-PCR and insulated isothermal RT-PCR for the detection of Rotavirus group A (RVA) in feces of different animal species. AB - There is no gold standard for detection of Rotavirus Group A (RVA), one of the main causes of diarrhea in neonatal animals. Sensitive and specific real-time RT PCR (rtRT-PCR) assays are available for RVA but require submission of the clinical samples to diagnostic laboratories. Patient-side immunoassays for RVA protein detection have shown variable results, particularly with samples from unintended species. A sensitive and specific test for detection of RVA on the farm would facilitate rapid management decisions. The insulated isothermal RT-PCR (RT-iiPCR) assay works in a portable machine to allow sensitive and specific on site testing. The aim of this investigation was to evaluate a commercially available RT-iiPCR assay for RVA detection in feces from different animal species. This assay was compared to an in-house rtRT-PCR assay and a commercially available rtRT-PCR kit, as well as an ELISA and EM for RVA detection. All three PCR assays targeted the well-conserved NSP5 gene. Clinical fecal samples from 108 diarrheic animals (mainly cattle and horses) were tested. The percentage of positive samples by ELISA, EM, in-house rtRT-PCR, commercial rtRT-PCR, and RT iiPCR was 29.4%, 31%, 36.7%, 51.4%, 56.9%, respectively. The agreement between different assays was high (81.3-100%) in samples containing high viral loads. The sensitivity of the RT-iiPCR assay appeared to be higher than the commercially available rtRT-PCR assay, with a limit of detection (95% confidence index) of 3-4 copies of in vitro transcribed dsRNA. In conclusion, the user-friendly, field deployable RT-iiPCR system holds substantial promise for on-site detection of RVA. PMID- 27180039 TI - A new real-time RT-qPCR assay for the detection, subtyping and quantification of human respiratory syncytial viruses positive- and negative-sense RNAs. AB - Human respiratory syncytial virus (RSV) is a major health problem and the main cause of hospitalization due to bronchiolitis. RSV is divided into two antigenic subgroups, RSV-A and -B that co-circulate worldwide. Rapid and sensitive detection is desirable for proper patient handling while assessment of viral load may help to evaluate disease severity and progression. Finally RSV subtyping is needed to determine the prevalence and pathogenicity of each RSV subgroup, as well as their sensitivity to treatment. In this study, we took into account the most recent circulating RSV variants and designed two quantitative TaqMan one step RT-PCR assays to detect and quantify both RSV subgroups separately. Standard dilutions of transcripts of positive and negative polarities were included in the assay validation to assess potential differences in sensitivity on negative-sense genomes and positive-sense RNAs. In addition, RSV detection in respiratory specimens of different types and sampled in different populations was compared to commercially available RSV diagnostic tools. Altogether, the RSV-A and -B assays revealed sensitive and quantitative over a wide range of viral loads, with a slight improved sensitivity of the RSV-B assay on positive sense transcripts, and allowed accurate RSV subtyping. We thus provide a useful tool for both RSV diagnostics and research. PMID- 27180040 TI - High yield expression and purification of Chikungunya virus E2 recombinant protein and its evaluation for serodiagnosis. AB - Disease caused by Chikungunya virus (CHIKV) is clinically characterized by sudden onset of fever and severe arthralgia, which may persist for weeks, months, or years after acute phase of the infection. CHIKV is spreading globally; in India it first appeared in the 1960s followed by a quiescent period and then a full blown remergence in 2006 and sporadic persistence since then. Despite a large number of commercially available diagnostic kits for CHIKV, clinical preparedness and diagnostics suffer from sub-optimal assays. An international diagnostic laboratory survey suggested that there is a critical need for improved CHIKV diagnostics especially in the early acute phase of illness. With the recent studies indicating that a vast majority of human humoral response in CHIKV infection is directed against E2 protein, this supports strong interest to develop CHIKV E2 based serological tests. However, methods to produce large amounts of CHIKV protein are limited. Here we report cloning, expression and purification methods for obtaining a truncated 37kDa Chikungunya E2 protein at a high yield of 65-70mg/l. We found that this purified protein can be reliably used in ELISA and western blot to detect CHIKV specific antibodies in sera from patients who were PCR or IgM positive. Thus, using this protocol, laboratories can make large quantities of purified protein that can be potentially used in CHIKV serological analysis. PMID- 27180042 TI - Corrigendum to "Tumor suppression effects of myoepithelial cells on mice breast cancer" [Eur. J. Pharmacol. 765 (2015) 171-178]. PMID- 27180041 TI - Analysis of loco-regional and distant recurrences in breast cancer after conservative surgery. AB - BACKGROUND: A number of patients treated conservatively for breast cancer will develop loco-regional and distant recurrences. Our aim was to determine how their occurrence may be linked to the evolution of the disease. METHODS: We analyzed 238 women treated by conservative breast surgery and breast irradiation in a single institution. We evaluated the prognostic factors associated with loco regional and distant recurrences and the prognostic value of local and regional recurrences on systemic progression. RESULTS: After a median follow-up of 5 year (range 1-10), 16 (6.72%) patients in the breast conservative surgery (BCS) groups had loco-regional recurrence. For distant recurrence, 10 (4.2%) patients had experienced distant recurrence. Lympho-vascular invasion (HR 2.55; 95% CI, 076 to 8.49) and an extensive intraductal component (HR, 2.22; 95% CI, 0.69 to 7.15) and nodal status are risk factors for loco-regional recurrence (LRR) after breast conservative therapy (BCT). Tumor size, nodal status, high histologic grade, and breast cancer diagnosed at a young age (<=35 years) are correlated with higher distant recurrence rates after BCT. CONCLUSIONS: Risk factors for LRR after BCS include lympho-vascular invasion, extensive inraductal component, and high nodal status, where as risk factors for distant recurrence include tumor size, nodal status, high histologic grade, and breast cancer diagnosed at a young age (<=35 years). PMID- 27180043 TI - Corrigendum to "Restoration of sirt1 function by pterostilbene attenuates hypoxia reoxygenation injury in cardiomyocytes" [Eur. J. Pharmacol. 776 (2016) 26-33]. PMID- 27180044 TI - Assessment of facial pain and headache before and after nasal polyposis surgery with the DyNaChron questionnaire. AB - OBJECTIVES: Facial pain/headache is reported in 16-67% of nasal polyposis (NP) patients. This wide range may be due to differences in assessment methods. The present prospective study assessed facial pain/headache and quality-of-life (QoL) impact before and after NP surgery. METHODS: Pain was assessed on the DyNaChron self-administered questionnaire in patients undergoing NP surgery, the day before the procedure (V0) and 6 weeks (V1) and 7 months (V2) after. All patients underwent the same nasalization procedure, sparing the middle turbinates when possible. The questionnaire extract comprised 1 item assessing pain, 13 assessing physical impact and 4 assessing psychosocial impact, with responses on visual analog scales (VAS) graded 0 (no discomfort) to 10 (unbearable discomfort). RESULTS: Sixty-three patients (mean age: 50.6+/-12.8 years; 32 male [50.8%], 31 female [49.2%]) were included. Thirty-seven patients (58.7%) had history of NP surgery. Fifty-two percent reported moderate to severe pain before surgery, 17.5% at 6 weeks, and 22.2% at 7 months. One-third reported no pain preoperatively, versus a half at 6 weeks and 7 months. Scores for the physical and psychosocial impact of pain were improved after surgery. CONCLUSION: Headache/facial pain is frequent in patients for whom NP surgery is indicated. Endoscopic surgery relieves the symptom and its physical and psychosocial impacts. However, one fifth of patients reported residual postoperative pain. PMID- 27180045 TI - Development of a new Emergency Medicine Spinal Immobilization Protocol for trauma patients and a test of applicability by German emergency care providers. AB - BACKGROUND: In order to match the challenges of quickly recognizing and treating any life-threatening injuries, the ABCDE principles were established for the assessment and treatment of trauma patients. The high priority of spine protection is emphasized by the fact that immobilization of the cervical spine is performed at the very first step in the ABCDE principles. Immobilization is typically performed to prevent or minimize secondary damage to the spinal cord if instability of the spinal column is suspected. Due to increasing reports about disadvantages of spinal immobilization, the indications for performing spinal immobilization must be refined. The aim of this study was (i) to develop a protocol that supports decision-making for spinal immobilization in adult trauma patients and (ii) to carry out the first applicability test by emergency medical personnel. METHODS: A structured literature search considering the literature from 1980 to 2014 was performed. Based on this literature and on the current guidelines, a new protocol that supports on scene decision-making for spinal immobilization has been developed. Parameters found in the literature concerning mechanisms and factors increasing the likelihood of spinal injury have been included in the new protocol. In order to test the applicability of the new protocol two surveys were performed on German emergency care providers by means of a questionnaire focused on correct decision-making if applying the protocol. RESULTS: Based on the current literature and guidelines, the Emergency Medicine Spinal Immobilization Protocol (E.M.S. IMMO Protocol) for adult trauma patients was developed. Following a fist applicability test involving 21 participants, the first version of the E.M.S. IMMO Protocol has to be graphically re-organized. A second applicability test comprised 50 participants with the current version of the protocol confirmed good applicability. Questions regarding immobilization of trauma patients could be answered properly using the E.M.S. IMMO Protocol. DISCUSSION: Current literature increasingly reports of disadvantages that may be associated with immobilization. Based on the requirements of the current guidelines, a new protocol that supports decision-making for indications for out of-hospital spinal immobilization has been developed in this study. In contrast to established protocols, the new protocol offers different options for immobilization as well as a decicion-support. CONCLUSIONS: The E.M.S. IMMO protocol provides a decision-support tool for indications for spinal immobilization in adult trauma patients that permits variable decision-making depending on the current condition of the trauma patient and the pattern of injuries for immobilization in general and for immobilization method in particular. PMID- 27180046 TI - Buckling up in Singapore: residency and other risk factors for seatbelt non compliance - a cross-sectional study based on trauma registry data. AB - BACKGROUND: Seatbelt non-compliance is a problem in middle income countries, and little is known about seatbelt compliance in populations with a high proportion of non-residents. This study analyses the profile of seatbelt non-compliance in Singapore based on trauma registry data from five of the six public hospitals. METHODS: This is a cross-sectional study of seatbelt compliance of patients aged over 18 years, attending the emergency departments of five public hospitals in Singapore after road collisions from 2011-2014. Seatbelt data was obtained from paramedic and patient history. RESULTS: There were 4,576 patients studied. Most were Singapore citizens (83.4 %) or permanent residents (2.4 %), with the largest non-resident groups from Malaysia, India, and China. Overall seatbelt compliance was 82.1 %. On univariate analysis, seatbelt compliance was higher in older patients (OR 1.02, 95 % CI 1.001-1.021, p < 0.0001); drivers, followed by front passengers (OR 0.65, 95 % CI 0.51-0.83, p < 0.0001), were more compliant than rear passengers (OR 0.08, 0.06-0.09, p < 0.0001); occupants of larger vehicle types (buses, heavy transport vehicles, minibuses and vans) were more non compliant compared to occupants of private cars and taxis. Morning peak travel (0700 h-0900 h) and being a non-resident were other risk factors for non compliance. On multivariable analysis, older age (OR 1.01, 95 % CI 1.001-1.014, p = 0.03) was associated with compliance, while non-residents from China (OR 0.43, 95 % CI 0.18-0.99, p = 0.05), seat position (front passenger compared to driver, OR 0.64, 95 % CI 0.48-0.85, p = 0.002; rear passenger compared to driver, OR 0.067, 95 % CI 0.05-0.09, p < 0.0001), vehicle type (bus compared to car, OR 0.04, 95 % CI 0.017-0.11, p < 0.0001, van compared to car, OR 0.55, 95 % CI 0.36 0.83, p = 0.004), and travel at morning peak periods were independent predictors of seatbelt non-compliance. When the sub-group of drivers was analysed, only vehicle type was a significant predictor of seatbelt compliance, with bus drivers least likely to be compliant to seatbelts (multivariable analysis, OR 0.057 compared to cars, 95 % CI 0.019-0.18, p < 0.0001). CONCLUSIONS: While overall seatbelt compliance in our study is high, efforts can be made to increase compliance for morning rush hour passengers, rear seat passengers, and occupants of buses, heavy transport vehicles, and vans or pickups. PMID- 27180047 TI - A case study of SMART attributes: a qualitative assessment of generalizability, retention rate, and trial quality. AB - BACKGROUND: Personalizing medical care is becoming increasingly popular, particularly mental health care. There is growing interest in formalizing medical decision making based on evolving patient symptoms in an evidence-based manner. To determine optimal sequencing of treatments, the sequences themselves must be studied; this may be accomplished by using a sequential multiple assignment randomized trial (SMART). It has been hypothesized that SMART studies may improve participant retention and generalizability. METHODS: We examine the hypotheses that SMART studies are more generalizable and have better retention than traditional randomized clinical trials via a case study of a SMART study of antipsychotic medications. We considered the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia study, comparing the trial participant characteristics and overall retention to those of comparable trials found via a review of all related trials conducted from 2000 onwards. RESULTS: A MEDLINE search returned 6435 results for primary screening; ultimately, 48 distinct trials were retained for analysis. The study population in CATIE was similar to, although perhaps less symptomatic than, the study populations of traditional randomized clinical trials (RCTs), suggesting no large gains in generalizability despite the pragmatic nature of the trial. However, CATIE did see good month-by-month retention. CONCLUSIONS: SMARTs offer the possibility of studying treatment sequences in a way that a series of traditional RCTs cannot. SMARTs may offer improved retention; however, this case study did not find evidence to suggest greater generalizability using this trial design. TRIAL REGISTRATION: ClinicalTrials.gov NCT00014001 . Registered on 6 April 2001. PMID- 27180048 TI - Numerical simulations of sonochemical production and oriented aggregation of BaTiO3 nanocrystals. AB - Numerical simulations of sonochemical production and oriented attachment of BaTiO3 nanocrystals are performed in aqueous solution with pH 14. It is suggested that most significant effect of ultrasound is the dissolution of Ti-based gel in aqueous solution. It results in the dissolution-precipitation mechanism in the production of BaTiO3 nanoparticles, while with mechanical stirring without ultrasound it is the in situ mechanism that BaTiO3 is gradually formed on Ti based gel. The oriented attachment of spherical BaTiO3 nanocrystals occurs by van der Waals torque (Casimir torque). Large aggregates of nanocrystals do not attach with each other as the repulsive double layer interaction is stronger for larger aggregates. For smaller spherical nanocrystals, the alignment of the crystal axes is less accurate due to more significant rotational Brownian motion of the nanocrystals. PMID- 27180049 TI - Do the distinct synaptic properties of VGLUTs shape pain? AB - The somatosensory system transmits touch, temperature, itch and pain. Three vesicular glutamate transporter isoforms mediate the release of glutamate throughout the mammalian nervous system with largely non-overlapping distributions and unique roles at the synapse. This review discusses the contribution of each of these essential transporters to circuits underlying pain and other somatosensory behaviors throughout postnatal development and in the adult. A better understanding of the individual contributions of the VGLUT isoforms could provide new avenues for therapeutic intervention. PMID- 27180050 TI - Structural and dynamic perspectives on the promiscuous transport activity of P glycoprotein. AB - The multidrug transporter P-glycoprotein (P-gp) is expressed in the blood-brain barrier endothelium where it effluxes a range of drug substrates, preventing their accumulation within the brain. P-gp has been studied extensively for 40 years because of its crucial role in the absorption, distribution, metabolism and elimination of a range of pharmaceutical compounds. Despite this, many aspects of the structure-function mechanism of P-gp are unresolved. Here we review the emerging role of molecular dynamics simulation techniques in our understanding of the membrane-embedded conformation of P-gp. We discuss its conformational plasticity in the presence and absence of ATP, and recent efforts to characterize the drug binding sites and uptake pathways. PMID- 27180051 TI - Altered expression of KCC2 in GABAergic interneuron contributes prenatal stress induced epileptic spasms in infant rat. AB - Long-term stress during pregnancy causes neurologic deficits to offspring with altered gamma-aminobutyric acid (GABA) system in the brain. However, it is not clear how prenatal stress affects the maturing GABAergic interneurons and the resulting abnormalities in infantile seizures. Here, we showed that prenatal stress alters the maturation of GABA inhibitory system using a seizure model induced by prenatal stress. Prenatal stress with betamethasone or acute immobilization stress (AIS) on gestational day 15 increased the seizure susceptibility to N-methyl-d-aspartate-triggered spasms on postnatal day 15. The expression of GABA was lower in the prenatally stressed group, which compromise the decrease of glutamate decarboxylase 67-immunopositive cells. Prenatal stress markedly decreased the expression of K(+)/Cl(-) co-transporter (KCC2) in the cortex. GABA induced membrane depolarization demonstrated prenatal stress models had significant higher membrane depolarization compared to control. GABA increased KCC2 expression in cultured cortex-containing slices. Taken together, our results showed that prenatal stress with betamethasone or AIS altered the maturation of GABAergic progenitors and resulted in the lack of GABA input, which in turn, decreased KCC2 expression and lowered seizure threshold. We conclude that delayed GABA excitatory/inhibitory shift would render the cortical neuronal circuit more susceptible to excitatory input in prenatal stress induced seizure. PMID- 27180052 TI - Distinct effect of CacyBP/SIP on the ERK1/2-CREB-BDNF pathway in undifferentiated and differentiated neuroblastoma NB2a cells. AB - CacyBP/SIP, a protein expressed to high extent in the brain, has been shown to act as ERK1/2 phosphatase in vitro and in cultured cells. It has been demonstrated recently that CacyBP/SIP can modulate the activity of some transcription factors in neurons and glioma cells. In the present work we have examined the effect of CacyBP/SIP overexpression and silencing on the phosphorylation/activity of ERK1/2 (pERK1/2) and CREB (pCREB) and on the level of BDNF mRNA in differentiated and undifferentiated neuroblastoma NB2a cells. We have shown that in undifferentiated cells the amount of pERK1/2 decreased upon CacyBP/SIP overexpression. Further studies have shown that the activity of CREB and the level of BDNF mRNA, downstream effectors of the ERK1/2 signaling pathway, also depended on the CacyBP/SIP level and strictly matched the level of pERK1/2. Interestingly, in differentiated NB2a cells, overexpression of CacyBP/SIP appeared to have a distinct effect on the pERK1/2 level from that observed in undifferentiated cells. Subsequent studies have revealed that distinct function of CacyBP/SIP in undifferentiated and differentiated NB2a cells might be due to changes in its posttranslational modifications and protein ligands. Altogether, our studies suggest that CacyBP/SIP is involved in the ERK1/2-CREB-BDNF pathway and that it might regulate this pathway depending on the stage of NB2a cell differentiation. PMID- 27180053 TI - Prognostic implications of epithelial to mesenchymal transition related proteins (E-cadherin, Snail) and hypoxia inducible factor 1alpha in endometrioid endometrial carcinoma. AB - The epithelial-mesenchymal transition (EMT) is an important step in the invasion and metastasis of cancer. E-cadherin downregulation, which is essentially controlled by EMT-mediated proteins such as Snail, is a main molecular feature of this process. Tumor hypoxia is one of the essential biological phenomena that are associated with the development and progression of various solid tumors. Recently, hypoxia and hypoxia-inducible factor 1alpha (HIF-1alpha) signaling pathway were identified to have an essential role in the regulation of EMT phenotype. The aim of the study was to evaluate the prognostic impact of EMT related proteins (E-cadherin, Snail) and HIF-1alpha in endometrioid endometrial carcinoma (EEC) among Egyptian women. Immunohistochemical evaluation of E cadherin, Snail, and HIF-1alpha expression was performed using 50 cases of EEC. The relationship between protein expression and clinicopathological features was investigated. The frequency of immunopositivity for E-cadherin, Snail, and HIF 1alpha in our cases of EEC was 82%, 28%, and 66%, respectively. Reduced E cadherin and increased nuclear expression of Snail as well as HIF-1alpha were significantly associated with histopathologic grade, clinical stage myometrial invasion, and lymph node involvement. Statistical analysis showed a positive correlation between HIF-1alpha overexpression and Snail upregulation (tau= +0.252, P= .025); however, E-cadherin expression level was inversely correlated with enhanced Snail expression (tau= -0.450, P< .001) as well as with HIF-1alpha overexpression (tau= -0.439, P< .001). The overall survival and progression-free survival were inversely related to Snail immunoreactivity and positively related to E-cadherin expression. E-cadherin and Snail have a predictive value in EEC. In conclusion, the current study reveals that both Snail and HIF-1alpha expressions are significantly associated with poor prognosis in EEC; however, E-cadherin expression is considered a marker of good prognosis. E-cadherin and Snail expression has a predictive value in EEC management. PMID- 27180054 TI - Myoepithelial differentiation in cribriform, tubular and solid pattern of adenoid cystic carcinoma: A potential involvement in histological grading and prognosis. AB - Adenoid cystic carcinoma (AdCC) is known as a biphasic tumor composed of ductal and myoepithelial cells. The present study aimed to evaluate the amount and distribution of the myoepithelial cells in cribriform, tubular and solid subtypes of AdCC and analyze their relationship with histological grading and prognosis. A panel of myoepithelial markers including CK5/6, p63, p40, D2-40, calponin, alpha SMA, S-100, and vimentin, together with a luminal cell marker CK7, and Ki-67 were used for immunohistochemical study in 109 AdCCs that included 38 cribriform, 36 tubular and 35 solid subtypes. The myoepithelial cells were labeled and found lined cystic-like paces, located at the periphery of the cribriform arrangements, and presented at the nonluminal cells of the two-layered tubular structures, while absent or dispersed in the solid pattern. Meantime, the solid subtype presented a higher proliferation rate assessed by mitotic count and Ki-67 labeling index, followed by poorer overall survival and recurrent-free survival. Furthermore, CK7 expression was found higher in solid pattern than in cribriform tubular subtype, which showed negative correlation with the myoepithelial markers including D2-40, Calponin, alpha-SMA, p63, p40 and vimentin. The solid pattern of AdCC showed gland differentiation but loss of myoepithelial differentiation with a higher proliferation and more aggressiveness as well as poorer prognosis compared with the cribriform-tubular subtypes, which implies that loss of MEC differentiation might contribute to the poor prognosis of the solid subtype of AdCC. However, further studies are required to clarify its exact role in AdCC progression. PMID- 27180055 TI - A novel marker of ameloblastoma and systematic review of immunohistochemical findings. AB - This study aims at investigating the pathogenesis and oncogenesis of ameloblastoma. Being the commonest odontogenic tumor with idiopathic nature, ameloblastoma poses a fierce controversy about its oncogenesis. Immunohistochemical markers, over years, have highlighted specific pathways which are inherently undertaken in the tumorigenic process of ameloblastoma. Besides the recently pronounced clue of BRAF V600E mutant gene, this study introduces a new marker with its outstanding impact on our contemporary knowledge about ameloblastoma. Extrapolating from the systematic review of medical literature and recruiting a novel immunohistochemical marker, ameloblastoma enacts a new scenario supporting the approved involvement of MAPK by overexpressing WT1 a total of 37 archival cases, regardless of the histological variant in study. There evinces a significant contribution of Wilm's tumor gene, as an oncogene rather than a suppressor gene, to the pathogenesis of the ameloblastomatous tumorigenesis. Moreover, no ameloblastomatous histological phenotype has established, given the literature underpinned, a concrete impact on the clinical behavior. Immunohistochemical research papers which investigated tumorigenesis - although they do not quantitatively measure much- had the most significant impact on the diagnostic and prognostic levels. WT1 may play, therefore, a remarkable role in the oncogenesis of ameloblastoma. PMID- 27180056 TI - Defining Ewing and Ewing-like small round cell tumors (SRCT): The need for molecular techniques in their categorization and differential diagnosis. A study of 200 cases. AB - BACKGROUND: Differentiation of Ewing sarcoma family of tumors (ESFT) and Ewing like tumors remains problematic. Certain ESFT with morphological and immunohistochemical (IHC) profiles lack the EWSR1-ETS transcript. To improve diagnostic accuracy we investigated the presence of several specific transcripts in 200 small round cell tumors (SRCT) displaying ESFT morphology and immunophenotype in which EWSR1 FISH analysis was non-informative or negative. DESIGN: 200 tumors (formalin-fixed, paraffin-embedded) were analyzed by RT-PCR. All tumors were tested for EWSR1-ETS, EWSR1/WT1, PAX3/7-FOX01 or SYT/SSX transcripts, and the negative tumors were subsequently analyzed for CIC/DUX4, BCOR/CCNB3 and CIC/FOX04 transcripts. RESULTS: 133 (66.5%) ESFT displayed one of the above EWSR1-ETS translocations. Three cases (1.5%) revealed the SYT-SSX transcript for Synovial sarcoma, and one (0.5%) a EWSR1-WT1 transcript for Desmoplastic Small Round Cell tumor. The CIC-DUX4 translocation was found in six Ewing-like tumors (3%) with CD99 positivity. The BCOR-CCNB3 gene fusion was observed in 5 tumors (2.5%) displaying round or spindle cells with strong CCNB3 IHC expression in 3 tumors. Moreover, RT-PCR failed to detect any gene fusion transcripts in 19 tumors (9.5%) and were considered "undifferentiated small round cell sarcoma" (SRCS). Molecular biology results were non-informative in 33 SRCTs (16.5%) due to RNA degradation through inadequate fixation and/or decalcification. CONCLUSION: Our analysis of 200 SRCTs confirms the molecular heterogeneity of neoplasms with ESFT morphology and highlight that molecular studies with RT-PCR including new emerging gene fusion transcripts are mandatory for the diagnosis when EWSR1 FISH is negative or non-informative. The incidence of CIC-DUX4, BCOR-CCNB3 and CIC-FOX04 transcripts was relatively low. A small group of Ewing-like sarcomas or undifferentiated SRCS remains unclassified. Adopting appropriate tissue fixation and processing protocols is important to avoid degradation of fixed/embedded tissue when no frozen tumor is available. PMID- 27180057 TI - Malakoplakia associated with prostatic adenocarcinoma: Report of 4 cases and literature review. AB - Malakoplakia is an inflammatory process that has been rarely reported in the prostate. Malakoplakia in association with prostatic carcinoma is exceedingly rare with only 4 previously reported cases. We describe the clinical features and the associated pathology in 4 patients who demonstrated malakoplakia of the prostate in association with prostatic adenocarcinoma. Prostatic malakoplakia presenting in association with prostatic adenocarcinoma was identified in 4 patients through a search from the records of 3 institutional databases with large in-house and consult uropathology practices. In 2 of the patients the diagnostic needle biopsy contained only prostatic carcinoma; malakoplakia in association with prostatic carcinoma was documented on prostatectomy, performed 15 and 8weeks after the biopsy, respectively. Both patients experienced urinary infections during the interval between the biopsy and the prostatectomy. The third and fourth patient had a long-standing history of "prostatitis", and acute urinary tract infection with urinary retention, respectively. The needle biopsy in both patients showed concomitant malakoplakia and prostatic carcinoma. One of them also had malakoplakia on the initial biopsy containing only atypical glands and on the subsequent one demonstrating carcinoma. One patient was treated conservatively and one with prostatectomy. Although coexistent prostatic carcinoma and malakoplakia are exceedingly rare, malakoplakia can likely occur as an exceptionally rare complication of a prostate needle biopsy, particularly in individuals with long-term or acute urinary tract infections at the time of the biopsy. PMID- 27180058 TI - Bmi-1 expression predicts prognosis in salivary adenoid cystic carcinoma and correlates with epithelial-mesenchymal transition-related factors. AB - Salivary adenoid cystic carcinoma (AdCC) is known for its high propensity to invade and metastasize. Bmi-1 acts as an oncogene by controlling cell cycle and self-renewal of adult stem cells, and its overexpression correlates with metastasis and poor prognosis in several cancers. Epithelial-mesenchymal transition (EMT) plays a central role in cancer metastasis. A key step in EMT is the down-regulation of E-cadherin that can be repressed by the transcriptional factors, such as Snail and Slug. In the present study, we investigated Bmi-1, Snail, Slug, and E-cadherin expression by immunohistochemistry in 102 patients with AdCC and analyzed statistically whether their expression correlated with clinicopathologic factors and prognosis. Reverse transcription-polymerase chain reaction was also performed in 22 tumor tissues and the adjacent noncancerous tissues to confirm Bmi-1 status in AdCCs. Our data demonstrated significant associations between the tumor metastasis and the expression of Bmi-1, Snail, Slug, and E-cadherin. Furthermore, a high level of Bmi-1 was not only correlated with the overexpression of Snail and Slug but also indicated an unfavorable metastasis-free survival and served as a high-risk marker for AdCC. In addition, Bmi-1 messenger RNA level was found much higher in AdCC tissues than in the adjacent noncancerous salivary gland tissues. Our results suggest that Bmi-1 may play a crucial role in AdCC progression by interaction with EMT-related markers and predict poor survival. PMID- 27180059 TI - Ectopic primary olfactory neuroblastoma of the maxillary sinus. AB - Olfactory neuroblastoma (ONB) is a rare malignant tumor. Although the vast majority of cases arise in the nasal cavity, ONB is rarely reported in ectopic locations. We report a case of ONB in the maxillary sinus. A 63-year-old woman presented with left-sided nasal obstruction and epistaxis. Magnetic resonance imaging showed a nonenhancing left maxillary sinus tumor. Histologic sections showed ONB, Hyams grade IV, invading bone, skeletal muscle, and adjacent fibroadipose tissue. It is essential to be accurate when diagnosing sinonasal tumors because the differential diagnosis is broad, and one must consider the possibility of ectopic ONB, although it is rare. The behavior of ONB and other neuroendocrine tumors of the sinonasal region is quite different, and there are varied approaches to treatment. Therefore, an accurate diagnosis as well as correct grade and stage must be assigned. PMID- 27180060 TI - Mammary analogue secretory carcinoma of salivary glands: a clinicopathologic study of 11 cases. AB - Mammary analogue secretory carcinoma (MASC) is a recently described tumor sharing the histologic, immunohistochemical, and molecular profile of secretory carcinoma of breast. We aimed to evaluate the morphologic and histochemical features needed/required for the diagnosis of MASC without adjunct of molecular analysis. Six retrospective cases suspicious for MASC and 5 prospective cases reported as MASC were included in the study. Molecular analysis of ETV6 by fluorescence in situ hybridization was performed at the University of Pittsburg, USA. The ages of the patients ranged from 9 to 60 years (mean, 27.5 years). Histologically, all tumors showed mixed growth patterns including microcystic, macrocystic, papillary, tubular, and solid, papillary the being most common pattern. The tumor cells showed round to oval vesicular nuclei with small nucleoli, and eosinophilic to vacuolated cytoplasm. All cases demonstrated luminal and cytoplasmic mucin on periodic acid-Schiff with and without diastase digestion and alcian blue stain. ETV6 fusion gene rearrangement by fluorescence in situ hybridization was detected in 10 of 11 tumors. Recurrences occurred in 3 patients, and 1 patient died of disease 5 years after surgery. In conclusion, MASC is a relatively rare salivary gland malignancy exhibiting distinct histologic and histochemical features which can help to differentiate it from other mimics. Histologically, papillary-cystic and microcystic patterns are the main clues to diagnosis. The follicular pattern of acinic cell carcinoma might represent MASC, as 4 cases in our series had this pattern. Two patients in our series were 9 and 91/2 years old respectively, which are the youngest ages ever recorded for MASC. PMID- 27180061 TI - Utility of peritoneal washing cytology in staging and prognosis of ovarian and fallopian tube neoplasms: a 10-year retrospective analysis. AB - The prognostic significance of peritoneal washing cytology in gynecologic neoplasms is controversial. The presence of neoplastic cells in peritoneal washings is currently part of the Federation of Gynecology and Obstetrics and American Joint Committee on Cancer TNM staging systems in cases of ovarian and fallopian tube neoplasms without metastasis beyond the pelvis. In this study, we retrospectively reviewed all cases of ovarian and fallopian tube neoplasms in which cytologic studies were performed. The utility of cytology in tumor staging and the relationship between cytology results and patient outcome are studied. All cases of ovarian and fallopian tube neoplasms in our institution between July 2002 and July 2012 were reviewed. Primary tumor characteristics including type and pelvic extension were collected, categorized, and correlated with peritoneal washing cytology. Final tumor staging was reviewed and the impact of positive cytology was evaluated. A total of 120 cases of ovarian and fallopian tube neoplasms without extrapelvic metastasis were identified within the study period. Peritoneal washing cytology was positive in 24% (29/120) of neoplasms and upstaged the tumor 83% (24/29) of the time when positive. Overall, 20% (24/120) of reviewed cases were upstaged based on positive cytology results. Peritoneal washing cytology remains a useful staging tool for ovarian and fallopian tube neoplasms limited to the pelvic cavity. Positive cytology results in upstaging in a significant proportion of the cases regardless of the tumor type. A larger study is needed to analyze follow-up data to determine if upstaging based on positive cytology adversely affects outcome. PMID- 27180062 TI - The correlation of sodium iodide symporter and BRAF(V600E) mutation in classical variant papillary thyroid carcinoma. AB - BRAF(V600E) mutation was analyzed by real-time polymerase chain reaction in 96 consecutive cases with classical variant papillary thyroid cancer, and immunohistochemical staining of Na+/I- symporter (NIS) protein was evaluated. Localization (intracellular or membranous), density, and the intensity of cytoplasmic staining were characterized semiquantitatively. Extrathyroidal invasion, surgical margin positivity, and lymph node metastasis were compared with BRAF(V600E) mutation and NIS expression. Eighty-eight patients who had at least 24-month follow-up were also included in survival analysis. BRAF(V600E) mutation was determined in 78.1% (75/96) and functional NIS activity in 74% (71/96) of the cases. There were statistically significant differences in mean ages between BRAF(V600E) mutation-positive (48.6) and BRAF(V600E) mutation negative cases (37.3; Levene test, P=.419; Student t test, P=.001). The surgical margin positivity (46.7%) and extrathyroidal extension percentage (54.7%) in the BRAF(V600E) mutation-positive group were higher than the negative (28.6% and 33.3%, respectively) group, without statistical significance (P=.138 and P=.084, respectively). Functional NIS activity was higher in BRAF(V600E) mutation positive cases (78.1%) than mutation-negative ones (57.1%; P=.047). The possibility of moderate and intense cytoplasmic staining in BRAF(V600E) mutation positive cases (72%) was 6.3 times higher than the possibility of weak staining (28%) in the mutation-positive cases (95% confidence interval, 2.2-18.8; P=.001). Functional NIS expression is higher in patients with classical variant papillary thyroid cancer with BRAF(V600E) mutation. However, the clinical features were not found to be associated with NIS expression. There may be different mechanisms determining the outcome of therapy. PMID- 27180063 TI - Tubulosquamous polyps in the vagina. Immunohistochemical comparison with ectopic prostatic tissue and Skene glands. AB - Two tubulosquamous polyps arising in the vagina are reported. Both were diffusely positive for GATA3 in the squamous component and focally positive for NKX3.1 in the glandular component, prostate acid phosphatase was focally positive in only 1 case in the glandular component. Both cases were negative for PAX2, PAX8, SALL4, and prostate-specific antigen. In addition, we included 3 cases of cervical squamous-lined cysts most likely representing ectopic prostatic tissue in the cervix and 1 case of paraurethral Skene-type glands to compare the immunophenotype. We analyze this immunoprofile, not previously reported. We also suggest unifying the nomenclature because vaginal Brenner tumors are most likely synonymous with tubulosquamous polyp (TSP) of the vagina. Our findings add support to the postulated origin of TSPs and cervical ectopic prostatic tissue from eutopic or misplaced Skene glands, equivalent of the prostate in the female. NKX3.1 seems a better marker to study and diagnose ectopic prostatic tissue in the cervix as well as TSPs. PMID- 27180064 TI - SRRM4 Drives Neuroendocrine Transdifferentiation of Prostate Adenocarcinoma Under Androgen Receptor Pathway Inhibition. AB - BACKGROUND: Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of castration-resistant prostate cancer that typically does not respond to androgen receptor pathway inhibition (ARPI), and its diagnosis is increasing. OBJECTIVE: To understand how NEPC develops and to identify driver genes to inform therapy for NEPC prevention. DESIGN, SETTING, AND PARTICIPANTS: Whole-transcriptome sequencing data were extracted from prostate tumors from two independent cohorts: The Beltran cohort contained 27 adenocarcinoma and five NEPC patient samples, and the Vancouver Prostate Centre cohort contained three patient samples and nine patient-derived xenografts. INTERVENTION: A novel bioinformatics tool, comparative alternative splicing detection (COMPAS), was invented to analyze alternative RNA splicing on RNA-sequencing data. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: COMPAS identified potential driver genes for NEPC development. Biochemical and biological validations were performed in both prostate cell and tumor models. RESULTS AND LIMITATION: More than 66% of the splice events were predicted to be regulated by the RNA splicing factor serine/arginine repetitive matrix 4 (SRRM4). In vitro and in vivo evidence confirmed that one SRRM4 target gene was the RE1 silencing transcription factor (REST), a master regulator of neurogenesis. Moreover, SRRM4 strongly stimulated adenocarcinoma cells to express NEPC biomarkers, and this effect was exacerbated by ARPI. ARPI combined with a gain of SRRM4-induced adenocarcinoma cells to assume multicellular spheroid morphology and was essential in establishing progressive NEPC xenografts. These SRRM4 actions were further enhanced by loss of function of TP53. CONCLUSIONS: SRRM4 drives NEPC progression. This knowledge may guide the development of novel therapeutics aimed at NEPC. PATIENT SUMMARY: Using next-generation RNA sequencing and our newly developed bioinformatics tool, we identified a neuroendocrine prostate cancer (NEPC)-specific RNA splicing signature that is predominantly controlled by serine/arginine repetitive matrix 4 (SRRM4). We confirmed that SRRM4 drives NEPC progression, and we propose SRRM4 as a potential therapeutic target for NEPC. PMID- 27180065 TI - Cardiorespiratory fitness is positively associated with increased pancreatic beta cell function independent of fatness in individuals with the metabolic syndrome: Fitness versus fatness. AB - OBJECTIVES: The vulnerability of individuals with the metabolic syndrome (MetS) to cardiovascular events (CVEs) is attenuated by increased cardiorespiratory fitness (CRF), despite the presence of obesity as a usual component of MetS. To better understand the importance of CRF and body fat in treating this condition, we investigated the relationship between fitness and fatness with pancreatic beta cell function (BCF) indices that are known independent predictors of CVEs. DESIGN: Cross sectional study. METHODS: This study included 84 individuals with MetS. BCF indices were derived from a fasted steady state (basal disposition index [DI], proinsulin, proinsulin:insulin, and proinsulin:C-peptide) and dynamic conditions via an oral glucose tolerance test (1st and 2nd phase DI). CRF and body fat percentage (BF%) were assessed via indirect calorimetry (during a maximal exercise test) and dual energy X-ray absorptiometry, respectively. RESULTS: CRF was positively associated with basal DI (r=0.40, p<0.001), 1st phase DI (r=0.49, p<0.005), and 2nd phase DI (r=0.38, p=0.02). Hierarchical multiple regression analysis showed CRF was associated with basal DI (beta=0.18, p=0.04), 1st phase DI (beta=0.36, p=0.04), and 2nd phase DI (beta=0.33, p=0.03), independent of BF% and other confounding factors including age, sex, diabetic status, anthropometric measures, lipid profile, and insulin sensitivity. No significant associations were found between CRF and proinsulin measures. BF% was not significantly correlated with BCF indices. CONCLUSIONS: Increased CRF was independently associated with enhanced BCF. This study provides evidence that equal, if not more attention should be dedicated to CRF improvement relative to fat-loss for favorable pancreatic BCF and thus possible reduction in CV risk in individuals with MetS. PMID- 27180067 TI - Health risk from veterinary antimicrobial use in China's food animal production and its reduction. AB - The overuse and misuse of veterinary drugs, particularly antimicrobials, in food animal production in China cause environmental pollution and wide food safety concerns, and pose public health risk with the selection of antimicrobial resistance (AMR) that can spread from animal populations to humans. Elevated abundance and diversity of antimicrobial resistance genes (ARGs) and resistant bacteria (including multi-drug resistant strains) in food-producing animals, food products of animal origin, microbiota of human gut, and environmental media impacted by intensive animal farming have been reported. To rein in drug use in food animal production and protect public health, the government made a total of 227 veterinary drugs, including 150 antimicrobial products, available only by prescription from licensed veterinarians for curing, controlling, and preventing animal diseases in March 2014. So far the regulatory ban on non-therapeutic use has failed to bring major changes to the long-standing practice of drug overuse and misuse in animal husbandry and aquaculture, and significant improvement in its implementation and enforcement is necessary. A range of measures, including improving access to veterinary services, strengthening supervision on veterinary drug production and distribution, increasing research and development efforts, and enhancing animal health management, are recommended to facilitate transition toward rational use of veterinary drugs, particularly antimicrobials, and to reduce the public health risk arising from AMR development in animal agriculture. PMID- 27180066 TI - Pharmacokinetics and Bioavailability of the GnRH Analogs in the Form of Solution and Zn2+-Suspension After Single Subcutaneous Injection in Female Rats. AB - BACKGROUND AND OBJECTIVES: Although many synthetic gonadoliberin analogs have been developed, only a few of them, including buserelin, were introduced into clinical practice. Dalarelin, which differs from buserelin by just one aminoacid in the position 6 (D-Ala), is not widely used so far. Gonadotropin-releasing hormone (GnRH) analogs are used to treat many different illnesses and are available in different forms like solution for injection, nasal spray, microspheres, etc. Unfortunately, none of the above drug formulations can release the hormones for 24 h. We assumed that classical suspension could solve this problem. METHODS: Two sets of experiments were performed. In the first one, buserelin and dalarelin were injected into mature female rats in two forms: suspension, in which the analogs are bounded by Zn2+ ions and solution. The pharmacokinetic parameters and bioavailability of the analogs were calculated, based on their concentration in the plasma measured by high-performance liquid chromatography method (HPLC). In the second experiment, the hormones in two different forms were injected into superovulated immature female rats and then the concentration of Luteinizing hormone (LH), Follicle-stimulating hormone (FSH) and 17beta-estradiol in the serum was measured by radioimmunological method. RESULTS: The Extent of Biological Availability (EBA), calculated on the base of AUC0-infinity, showed that in the form of solution buserelin and dalarelin display, respectively, only 13 and 8 % of biological availability of their suspension counterparts. Comparing both analogs, the EBA of dalarelin was half (53 %) that of buserelin delivered in the form of solution and 83 % when they were delivered in the form of suspension. The injection of buserelin or dalarelin, in the form of solution or suspension, into superovulated female rats increased LH, FSH and estradiol concentration in the serum. However, after injection of the analogs in the form of suspension, the high concentration of LH and FSH in the serum persisted longer. CONCLUSION: Performed studies indicate that GnRH analogs in the form of suspension have higher bioavailability than their solution counterparts. It influences the effects of their action, especially in relation to LH and FSH. PMID- 27180069 TI - Challenges and strategies of surface modification of electrogalvanized coatings for electron microscopy analysis. AB - Despite wide usage of electrogalvanized coatings in various applications, characterization studies on their micro/crystal structure, and the understanding of how they correspondingly affect the properties, such as corrosion, are rather limited. This is mainly attributed to some difficulties in preparing and examining the zinc coating layers, owing to their intrinsically low corrosion resistance and refined nano-scaled crystallite size. This study aims to examine such challenges systematically and propose some mitigation strategies. Particularly, sample preparation processes, including surface finishing for metallography and sample thinning processes are explored. Furthermore, a range of electron microscopy techniques, including scanning electron microscopy (SEM), electron back scattered diffractometry (EBSD), and transmission electron microscopy (TEM) are investigated in relation to the achievable clarity of microstructural details of electrogalvanized coatings. PMID- 27180068 TI - Melatonin for Sleep Disorders in Patients with Neurodegenerative Diseases. AB - In patients with neurodegenerative diseases, sleep disorders are common; they impair the quality of life for patients and caregivers and are associated with poorer clinical outcomes. Melatonin has circadian, hypnotic, and free radical scavenging effects, and preclinical data suggest benefits of melatonin on neurodegeneration. However, randomized, controlled trials of melatonin in patients with neurodegenerative diseases have not shown strong effects. Trials in Alzheimer's patients demonstrate a lack of benefit on sleep quantity. Subjective measures of sleep quality are mixed, with possible symptomatic improvements seen only on some measures or at some time points. Benefits on cognition have not been observed across several studies. In Parkinson's patients, there may be minimal benefit on objective sleep measures, but a suggestion of subjective benefit in few, small studies. Effective treatments for the sleep disorders associated with neurodegenerative diseases are urgently needed, but current data are insufficient to establish melatonin as such a treatment. PMID- 27180070 TI - Poor awareness of inflammatory back pain and axial spondyloarthritis among secondary care specialists. PMID- 27180071 TI - MicroRNA-338 Attenuates Cortical Neuronal Outgrowth by Modulating the Expression of Axon Guidance Genes. AB - MicroRNAs (miRs) are small non-coding RNAs that confer robustness to gene networks through post-transcriptional gene regulation. Previously, we identified miR-338 as a modulator of axonal outgrowth in sympathetic neurons. In the current study, we examined the role of miR-338 in the development of cortical neurons and uncovered its downstream mRNA targets. Long-term inhibition of miR-338 during neuronal differentiation resulted in reduced dendritic complexity and altered dendritic spine morphology. Furthermore, monitoring axon outgrowth in cortical cells revealed that miR-338 overexpression decreased, whereas inhibition of miR 338 increased axonal length. To identify gene targets mediating the observed phenotype, we inhibited miR-338 in cortical neurons and performed whole transcriptome analysis. Pathway analysis revealed that miR-338 modulates a subset of transcripts involved in the axonal guidance machinery by means of direct and indirect gene targeting. Collectively, our results implicate miR-338 as a novel regulator of cortical neuronal maturation by fine-tuning the expression of gene networks governing cortical outgrowth. PMID- 27180073 TI - Differential genotoxicity mechanisms of silver nanoparticles and silver ions. AB - In spite of many reports on the toxicity of silver nanoparticles (AgNPs), the mechanisms underlying the toxicity are far from clear. A key question is whether the observed toxicity comes from the silver ions (Ag+) released from the AgNPs or from the nanoparticles themselves. In this study, we explored the genotoxicity and the genotoxicity mechanisms of Ag+ and AgNPs. Human TK6 cells were treated with 5 nM AgNPs or silver nitrate (AgNO3) to evaluate their genotoxicity and induction of oxidative stress. AgNPs and AgNO3 induced cytotoxicity and genotoxicity in a similar range of concentrations (1.00-1.75 ug/ml) when evaluated using the micronucleus assay, and both induced oxidative stress by measuring the gene expression and reactive oxygen species in the treated cells. Addition of N-acetylcysteine (NAC, an Ag+ chelator) to the treatments significantly decreased genotoxicity of Ag+, but not AgNPs, while addition of Trolox (a free radical scavenger) to the treatment efficiently decreased the genotoxicity of both agents. In addition, the Ag+ released from the highest concentration of AgNPs used for the treatment was measured. Only 0.5 % of the AgNPs were ionized in the culture medium and the released silver ions were neither cytotoxic nor genotoxic at this concentration. Further analysis using electron spin resonance demonstrated that AgNPs produced hydroxyl radicals directly, while AgNO3 did not. These results indicated that although both AgNPs and Ag+ can cause genotoxicity via oxidative stress, the mechanisms are different, and the nanoparticles, but not the released ions, mainly contribute to the genotoxicity of AgNPs. PMID- 27180074 TI - On a path to accelerate access to Ebola vaccines: The WHO's research and development efforts during the 2014-2016 Ebola epidemic in West Africa. AB - During 2014 and 2015 an outbreak of Ebola deemed a Public Health Emergency of International Concern affected a number of West African countries. The outbreak underscored the need for a vaccine against Ebola. An unprecedented and to great extent collaborative effort built on the availability of a number of candidate vaccines that could enter into clinical phase evaluation. A series of international consultations and activities were led by WHO as a contribution to the unprecedented global efforts to develop and assess an Ebola vaccine. WHO consulted widely, and immediately fostered interactions with the international scientific, ethics, regulatory, vaccine development, public health partners, industry and funders' communities and participated in consortia to facilitate Ebola vaccine assessments. WHO also fostered key activities to ensure the optimal policy and deployment of Ebola vaccines, if licensed. WHO has convened a broad global coalition of experts to develop a Blueprint and a platform for accelerated R&D, in order to avert full-blown epidemics. PMID- 27180072 TI - Glutamate Inhibits the Pro-Survival Effects of Insulin-Like Growth Factor-1 on Retinal Ganglion Cells in Hypoxic Neonatal Rat Retina. AB - Glutamate that accumulates in injured brain tissue has been shown to hinder the neuroprotection rendered by insulin-like growth factor-1 (IGF-1). However, its role in attenuating the neuroprotective effect of IGF-1 in the hypoxic retina is unknown and the current study was aimed at elucidating this. One-day-old Wistar rats were exposed to hypoxia for 2 h and the retinas were studied at 3 h to 14 days after exposure. Following hypoxia, the concentrations of glutamate and IGF-1 were significantly increased over control values in the immature retina and in cultured retinal ganglion cells (RGCs). In addition to IGF-1, the relative expression of insulin receptor substrate-1 (IRS1) phosphorylated at the tyrosine residue (p-IRS1tyr), phosphorylated protein kinase B (p-AKT) and phosphorylated protein kinase A (p-PKA), which are involved in IGF-1 signalling, was also studied in hypoxic retinas and in cultured RGCs. Glutamate-mediated inhibition of the IGF-1 pathway in hypoxic RGCs was evident with a reduced expression of p IRS1tyr and p-AKT and an increased expression of p-PKA. However, the addition of exogenous IGF-1 reversed this. Glutamate enables the phosphorylation of IRS1 at the serine residue (p-IRS1ser) through a PKA-dependent pathway. The increased expression of p-IRS1ser and its increased association with IGF-1 receptors in hypoxic RGCs suggested a possible interference by glutamate with the IGF-1 pathway. Moreover, there was increased caspase-3/7 activity in hypoxic RGCs. These results suggest that glutamate, by blocking IGF-1-mediated neuroprotection, could cause the apoptosis of RGCs in the hypoxic neonatal retina. PMID- 27180075 TI - Comment on: Acupressure in insomnia and other sleep disorders in elderly institutionalized patients suffering from Alzheimer's disease. PMID- 27180076 TI - Editorial Comment. PMID- 27180077 TI - Editorial Comment. PMID- 27180078 TI - Reply by Authors. PMID- 27180079 TI - Editorial Comment. PMID- 27180080 TI - Special Issue - Spotlight on Cardiovascular Imaging. PMID- 27180081 TI - MRI findings in intraspinal mature teratoma. AB - AIM: To characterise and evaluate magnetic resonance imaging (MRI) images for their clinical value in diagnosing and assessing intraspinal mature teratoma. MATERIALS AND METHODS: MRI images obtained from eight patients with a histopathologically verified intraspinal mature teratoma were analysed retrospectively regarding tumour location, size, and margins. Additionally, the signal intensity and enhancement pattern on MRI and other associated malformations were also assessed. RESULTS: Three cases that contained fatty tissue showed markedly heterogeneous hyperintense signalling on T1-weighted images, and mixed hyperintense and hypointense signalling on T2-weighted images and fat-suppression sequences. All three of those cases showed an irregular peripheral fatty tissue signal, and one case showed additional patches of an interspersed calcification signal. The remaining five cases without fatty tissue displayed heterogeneous hyperintense signalling on T1-weighted images and T2 weighted images, and also on fat-suppression sequences. Four of the five cases showed additional patches of interspersed nodular calcification signals. Contrast enhanced MRI images showed only slight enhancement (n=3). CONCLUSIONS: MRI is regarded as the reference standard diagnostic technique to reveal the location of teratomas and the degree of spinal cord involvement. In most cases, MRI provides accurate anatomical and histological information, which is necessary for patients with suspected intraspinal mature teratoma. PMID- 27180082 TI - Radiation dose reduction in cardiovascular CT angiography with iterative reconstruction (AIDR 3D) in a swine model: a model of paediatric cardiac imaging. AB - AIM: To investigate the potential dose reduction in cardiovascular computed tomography angiography (CTA) in a swine model using 320-detector volume CT with adaptive iterative dose reduction in three dimensions (AIDR 3D) reconstruction to maintain a comparable image quality (IQ) to that reconstructed by a conventional filtered back projection (FBP) algorithm. METHODS AND MATERIALS: Twenty-four mini pigs underwent cardiovascular CTA four times at 80 KVp and different tube currents. An automatic exposure control (AEC) system was used and the noise index (NI) was predetermined at a standard deviation (SD) of 20 (Method A, routine dose), and 25, 30, 35 (Methods B-D) to reduce the dose gradually. Method A was reconstructed with FBP. Methods B-D were reconstructed using AIDR 3D (strong). Two radiologists graded IQ by reviewing both cardiac and vascular structures using a five-point scale. Quantitative IQ parameters of image noise, signal-to noise ratio (SNR), and contrast-to-noise ratio (CNR) were measured and compared. A receiver-operating characteristic (ROC) analysis was performed to select a radiation reduction threshold and maintain comparable IQ (score >=4). RESULTS: Method B and C had significantly lower image noise (p<0.0001), higher CNR and SNR than Method A (p<0.0001). Compared with Method A (noise: 52.7+/-8.3; SNR: 11.7+/ 2.8; and CNR: 9.9+/-2.7), Method C had comparable subjective IQ and higher objective IQ (noise: 38.9+/-6.1; SNR: 16.3+/-3.5; and CNR: 13.5+/-3.3). The results of the ROC curve showed that Method C (SD30) was the optimal dose threshold to maintain a comparable subjective IQ (AUC: 0.85, 95% confidence interval [CI]: 0.80-0.90). The effective dose (ED) of Method C was reduced by 49%, compared to that of Method A (0.33+/-0.08 mSv versus 0.65+/-0.15 mSv). CONCLUSION: AIDR 3D at a strong level combined with an AEC system can potentially reduce the ED by 49% and maintain an IQ comparable to that achieved using a routine-dose and FBP reconstruction in mini-pig cardiovascular CTA. PMID- 27180083 TI - Morphometric MRI changes in intracranial hypertension due to cerebral venous thrombosis: a retrospective imaging study. AB - AIM: To evaluate whether some magnetic resonance imaging (MRI) signs suggesting idiopathic intracranial hypertension (IIH) could also be found in intracranial hypertension (IH) due to cerebral venous thrombosis (CVT) and to assess their possible contribution to diagnosing this disorder. MATERIALS AND METHODS: Thirty one patients with IH due to CVT were evaluated prospectively using MRI. A group of 33 age- and sex-matched healthy volunteers served as controls. The optic nerve and sheath, pituitary gland, and ventricles were assessed. The prevalence of each imaging feature was compared between the two groups. RESULTS: Optic nerve sheath (ONS) dilatation and decreased pituitary gland height were the most valid signs suggesting IH in CVT patients: sensitivity 70.97% and 87.1%, respectively; specificity 96.97% and 72.73%, respectively; area under the curve 0.840 and 0.809, respectively. The MRI finding that showed the strongest association with IH in CVT patients was ONS dilatation (odds ratio 78.5). CONCLUSIONS: The combination of T1-weighted volumetric MRI and magnetic resonance venography could be helpful for diagnosing IH with CVT. Abnormalities of the ONS and the pituitary gland were reliable diagnostic signs for IH due to CVT. PMID- 27180085 TI - Characterization of alpha-humulene synthases responsible for the production of sesquiterpenes induced by methyl jasmonate in Aquilaria cell culture. AB - The resinous portions of Aquilaria and Gyrinops plants are known as 'agarwood' and have a distinctive fragrance. To examine the biosynthesis of these fragrant compounds, we previously established cell cultures of Aquilaria crassna in which the production of three sesquiterpenes (alpha-guaiene, alpha-humulene, and delta guaiene) could be induced by methyl jasmonate (MJ), and showed that cloned delta guaiene synthase from MJ-treated cells is involved in the synthesis of these three compounds, although only very small amounts of alpha-humulene are produced. In the present study, cDNAs encoding alpha-humulene synthases were also isolated. Three putative sesquiterpene synthase clones (AcHS1-3) isolated from the MJ treated cells had very similar amino acid sequences and shared 52 % identity with delta-guaiene synthases. The recombinant enzymes catalyzed the formation of alpha humulene as a major product. Expression of transcripts of the alpha-humulene synthase and delta-guaiene synthase genes in cultured cells increased after treatment with MJ. These results revealed that these alpha-humulene and delta guaiene synthases are involved in the synthesis of three sesquiterpenes induced by MJ treatment. PMID- 27180086 TI - Methylmercury alters glutathione homeostasis by inhibiting glutaredoxin 1 and enhancing glutathione biosynthesis in cultured human astrocytoma cells. AB - Methylmercury (MeHg) is a neurotoxin that binds strongly to thiol residues on protein and low molecular weight molecules like reduced glutathione (GSH). The mechanism of its effects on GSH homeostasis particularly at environmentally relevant low doses is not fully known. We hypothesized that exposure to MeHg would lead to a depletion of reduced glutathione (GSH) and an accumulation of glutathione disulfide (GSSG) leading to alterations in S-glutathionylation of proteins. Our results showed exposure to low concentrations of MeHg (1MUM) did not significantly alter GSH levels but increased GSSG levels by ~12-fold. This effect was associated with a significant increase in total cellular glutathione content and a decrease in GSH/GSSG. Immunoblot analyses revealed that proteins involved in glutathione synthesis were upregulated accounting for the increase in cellular glutathione. This was associated an increase in cellular Nrf2 protein levels which is required to induce the expression of antioxidant genes in response to cellular stress. Intriguingly, we noted that a key enzyme involved in reversing protein S-glutathionylation and maintaining glutathione homeostasis, glutaredoxin-1 (Grx1), was inhibited by ~50%. MeHg treatment also increased the S glutathionylation of a high molecular weight protein. This observation is consistent with the inhibition of Grx1 and elevated H2O2 production however; contrary to our original hypothesis we found few S-glutathionylated proteins in the astrocytoma cells. Collectively, MeHg affects multiple arms of glutathione homeostasis ranging from pool management to protein S-glutathionylation and Grx1 activity. PMID- 27180084 TI - Chemical constituents from Inonotus obliquus and their antitumor activities. AB - Four new lanostane-type triterpenes (inonotusanes D-G, 1-4), including a 24,25,26,27-tetranorlanostane, together with 11 known compounds (5-15), including 7 lanostane derivatives, 2 steroids and 2 aromatic compounds, were isolated from the sclerotia of Inonotus obliquus. Their structures were elucidated by 1D and 2D NMR spectroscopy and HRMS. To our knowledge, 1 is the first 24,25,26,27 tetranorlanostane-type triterpenoid from fungus, and this is the first time that 31-member lanostane-type triterpenes, 5 and 6, have been isolated from the sclerotia of I. obliquus instead of from its submerged culture. 7 and 8 are also new isolates of this genus. Compounds 1, 8, 12 and 13 exhibited strong cytotoxicity against the 4T1 (mouse breast cancer) cell line, with IC50 9.40, 7.79, 9.06 and 9.31 MUM, respectively. 8, 12 and 13 also exhibited strong cytotoxicity against the the MCF-7 (human breast cancer) cell line, with IC50 8.35-9.01 MUM. PMID- 27180087 TI - Mainstream cigarette smoke accelerates the progression of nonalcoholic steatohepatitis by modulating Kupffer cell-mediated hepatocellular apoptosis in adolescent mice. AB - Cigarette smoking in adolescents is considered to be a major cause of preventable morbidity and mortality. The purpose of this study is to investigate the role of mainstream cigarette smoke (MSCS) on the progression of nonalcoholic steatohepatitis in adolescents. Three-week-old C57BL/6 mice were fed either a methionine and choline-deficient plus high fat (MCDHF) diet for 6 weeks. Each group was exposed to MSCS (300, 600 ug/L) or fresh air for 2h per day during the first 3 weeks of MCDHF diet feeding. MSCS increased MCDHF diet-induced NASH by increasing serum ALT/AST levels, steatosis, inflammation, and fibrosis. Furthermore, MSCS was associated with the degree of oxidative stress and hepatocellular apoptosis in NASH mice, but not prominent in controls. In vitro, cigarette smoke extract (CSE) activated Kupffer cells (KCs) to release inflammatory cytokines and oxidative stress, which induced hepatocellular apoptosis. In conclusion, MSCS exposure accelerates the progression and severity of NASH by modulating KC-mediated hepatocellular apoptosis. Our results support the regulation of CS in adolescents with steatohepatitis. PMID- 27180089 TI - Reprogramming of nonfermentative metabolism by stress-responsive transcription factors in the yeast Saccharomyces cerevisiae. AB - The fundamental questions of how cells control growth and respond to stresses have captivated scientists for years. Despite the complexity of these cellular processes, we could approach this puzzle by asking our favorite model yeast, Saccharomyces cerevisiae, how it makes a critical decision to either proliferate, to rest in a quiescent state or to program itself to die. This review highlights the essentiality of transcriptional factors in the reprogramming of gene expression as a prime mechanism of cellular stress responses. A whelm of evidence shows that transcriptional factors allow cells to acquire appropriate and unified responses to the transmitted signals. They function to modulate pathway-specific gene expression and organize transcriptomic responses to the altered environments. This review is aimed to summarize current knowledge on the roles of novel and well-known yeast transcription factors in the control of growth and stress responses during glucose deprivation as a prototypical case study. The scope includes stress sensing, transcription factors' identity, gene regulation and proposed crosstalks between pathways, associated with stress responses. A complex commander system of multiple stress-responsive transcription factors, observed here and elsewhere, indicates that regulation of glucose starvation/diauxic shift is a highly sophisticated and well-controlled process, involving elaborative networks of different kinase/target proteins. Using S. cerevisiae as a model, basic genetic research studies on gene identification have once again proved to be essential in the comprehension of molecular basis of cellular stress responses. Insights into this fundamental and highly conserved phenomenon will endow important prospective impacts on biotechnological applications and healthcare improvement. PMID- 27180090 TI - TOX expression in cutaneous B-cell lymphomas. AB - Thymocyte selection-associated high-mobility group box (TOX) is aberrantly expressed in cutaneous T-cell lymphomas. In a recent study, TOX expression was noted unexpectedly in the follicle center (germinal center) B-cells of reactive lymph nodes and tonsils, used as external controls. To evaluate whether TOX is also expressed by cutaneous B-cell lymphomas, TOX immunohistochemistry was performed on skin biopsies of 44 patients with primary and secondary cutaneous B cell proliferations. TOX was expressed not only in the reactive follicle center cells of lymph nodes, tonsils, cutaneous lymphoid hyperplasia, and primary cutaneous marginal zone lymphomas, but also by the neoplastic follicle center cells of 16/17 patients with primary cutaneous follicle center lymphoma (PCFCL) and 7/7 patients with cutaneous manifestations of systemic follicular lymphoma (FL). Notably, TOX showed a very similar expression pattern as BCL6, a marker of germinal center B-cells. In 4/10 patients with a BCL6(+) primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL,LT) and in 2/2 patients with a secondary cutaneous BCL6(+) diffuse large B-cell lymphoma (DLBCL), TOX was expressed by more than 50 % of the neoplastic B-cells. In contrast, in 3/3 BCL6( ) PCDLBCL,LT, TOX was completely negative or weakly expressed by a minor proportion of the neoplastic B-cells. In conclusion, TOX is expressed not only by neoplastic T-cells, but also by both reactive and neoplastic follicle center (germinal center) B-cells and a proportion of BCL6(+) PCDLBCL,LT and secondary cutaneous BCL6(+) DLBCL. The functional significance of TOX expression in reactive and neoplastic B-cells remains to be elucidated. PMID- 27180088 TI - The SOMATICS collaborative: Introduction to a National Institute on Drug Abuse cooperative study of pharmacotherapy for opioid treatment in criminal justice settings. AB - BACKGROUND: Among the nearly 750,000 inmates in U.S. jails, 12% report using opioids regularly, 8% report use in the month prior to their offense, and 4% report use at the time of their offense. Although ample evidence exists that medications effectively treat Opiate Use Disorder (OUD) in the community, strong evidence is lacking in jail settings. The general lack of medications for OUD in jail settings may place persons suffering from OUD at high risk for relapse to drug use and overdose following release from jail. METHODS: The three study sites in this collaborative are pooling data for secondary analyses from three open label randomized effectiveness trials comparing: (1) the initiation of extended release naltrexone [XR-NTX] in Sites 1 and 2 and interim methadone in Site 3 with enhanced treatment-as usual (ETAU); (2) the additional benefit of patient navigation plus medications at Sites 2 and 3 vs. medication alone vs. ETAU. Participants are adults with OUD incarcerated in jail and transitioning to the community. RESULTS: We describe the rationale, specific aims, and designs of three separate studies harmonized to enhance their scientific yield to investigate how to best prevent jail inmates from relapsing to opioid use and associated problems as they transition back to the community. CONCLUSIONS: Conducting drug abuse research during incarceration is challenging and study designs with data harmonization across different sites can increase the potential value of research to develop effective treatments for individuals in jail with OUD. PMID- 27180092 TI - Total Mucosal Irradiation with Intensity-modulated Radiotherapy in Patients with Head and Neck Carcinoma of Unknown Primary: A Pooled Analysis of Two Prospective Studies. AB - AIMS: To determine the clinical outcomes of an intensity-modulated radiotherapy technique for total mucosal irradiation (TM-IMRT) in patients with head and neck carcinoma of unknown primary (HNCUP). MATERIALS AND METHODS: A single-centre prospective phase II trial design was used in two sequential studies to evaluate TM-IMRT for HNCUP. Patients were investigated for primary tumour site using examination under anaesthetic and biopsies, computed tomography +/- magnetic resonance imaging (MRI) or 18-fluorodeoxyglucose positron emission tomography computed tomography (PET-CT). Patients received IMRT to the potential primary tumour sites and elective cervical nodes. Concomitant chemotherapy was used in patients who received primary radiotherapy or those with nodal extracapsular extension. RESULTS: Thirty-six patients with HNCUP were recruited; 72% male. Twenty-five patients (69.4%) had p16-positive disease. Two year mucosal and local nodal control rates were 97.1% (95% confidence interval 91.4-100) and 89.8% (78.4 100), respectively. One mucosal primary was detected 7.3 months after TM-IMRT and three patients died from recurrent/metastatic squamous cell carcinoma of the head and neck. Twelve patients (33%) developed grade 3 (Late Effects in Normal Tissue Subjective, Objective, Management and Analytical; LENT-SOMA) dysphagia with a 1 year enteric tube feeding rate of 2.7%. The high-grade subjective xerostomia rate (LENT-SOMA) at 24 months after IMRT was 15%. CONCLUSIONS: At a median follow-up of 36.1 months, the use of TM-IMRT was associated with good local control. Toxicity was comparable with previously reported TM-IMRT regimens encompassing similar mucosal volumes. PMID- 27180091 TI - Pseudoprogression in children, adolescents and young adults with non-brainstem high grade glioma and diffuse intrinsic pontine glioma. AB - Pseudoprogression (PsP) is a treatment-related phenomenon which hinders response interpretation. Its prevalence and clinical impact have not been evaluated in children/adolescents. We assessed the characteristics, risk factors and prognosis of PsP in children/adolescents and young-adults diagnosed with non-brainstem high grade gliomas (HGG) and diffuse intrinsic pontine gliomas (DIPG). Patients aged 1 21 years diagnosed with HGG or DIPG between 1995 and 2012 who had completed radiotherapy were eligible. PsP was assessed according to study-specific criteria and correlated with first-line treatment, molecular biomarkers and survival. Ninety-one patients (47 HGG, 44 DIPG) were evaluable. Median age: 10 years (range, 2-20). Eleven episodes of PsP were observed in 10 patients (4 HGG, 6 DIPG). Rates of PsP: 8.5 % (HGG); 13.6 % (DIPG). Two episodes of PsP were based on clinical findings alone; nine episodes had concurrent radiological changes: increased size of lesions (n = 5), new focal enhancement (n = 4). Temozolomide, MGMT methylation or H3F3A mutations were not found to be associated with increased occurrence of PsP. For HGG, 1-year progression-free survival (PFS) was 41.9 % no-PsP versus 100 % PsP (p = 0.041); differences in 1-year overall survival (OS) were not significant. For DIPG, differences in 1-year PFS and OS were not statistically significant. Hazard ratio (95 %CI) of PsP for OS was 0.551 (0.168-1.803; p = 0.325) in HGG; and 0.308 (0.107-0.882; p = 0.028) in DIPG. PsP occurred in both pediatric HGG and DIPG patients at a comparable rate to adult HGG. PsP was associated with improved 1-yr PFS in HGG patients. PsP had a protective effect upon OS in DIPG patients. PMID- 27180093 TI - Computational modeling and simulation of genital tubercle development. AB - Hypospadias is a developmental defect of urethral tube closure that has a complex etiology involving genetic and environmental factors, including anti-androgenic and estrogenic disrupting chemicals; however, little is known about the morphoregulatory consequences of androgen/estrogen balance during genital tubercle (GT) development. Computer models that predictively model sexual dimorphism of the GT may provide a useful resource to translate chemical-target bipartite networks and their developmental consequences across the human-relevant chemical universe. Here, we describe a multicellular agent-based model of genital tubercle (GT) development that simulates urethrogenesis from the sexually indifferent urethral plate stage to urethral tube closure. The prototype model, constructed in CompuCell3D, recapitulates key aspects of GT morphogenesis controlled by SHH, FGF10, and androgen pathways through modulation of stochastic cell behaviors, including differential adhesion, motility, proliferation, and apoptosis. Proper urethral tube closure in the model was shown to depend quantitatively on SHH- and FGF10-induced effects on mesenchymal proliferation and epithelial apoptosis-both ultimately linked to androgen signaling. In the absence of androgen, GT development was feminized and with partial androgen deficiency, the model resolved with incomplete urethral tube closure, thereby providing an in silico platform for probabilistic prediction of hypospadias risk across combinations of minor perturbations to the GT system at various stages of embryonic development. PMID- 27180094 TI - Strongyloides infections of humans and great apes in Dzanga-Sangha Protected Areas, Central African Republic and in degraded forest fragments in Bulindi, Uganda. AB - DNA sequence analysis was carried out on Strongyloides spp. larvae obtained from fecal samples of local humans, a wild western lowland gorilla (Gorilla gorilla gorilla) and a central chimpanzee (Pan troglodytes troglodytes) inhabiting Dzanga Sangha Protected Areas (DSPA), Central African Republic, and eastern chimpanzees (Pan troglodytes schweinfurthii) living in degraded forest fragments on farmland in Bulindi, Uganda. From humans, both Strongyloides fuelleborni and Strongyloides stercoralis were recorded, though the former was predominant. Only S. fuelleborni was present in the great apes in both areas. Phylogenetic analysis of partial mtDNA cytochrome c oxidase subunit 1 gene (Cox1) and comparison of 18S rDNA hyper variable region IV (HVR-IV) sequences implied that in DSPA S. fuelleborni populations in humans differ from those in the nonhuman great apes. PMID- 27180095 TI - Characterisation of the bacterial community structures in the intestine of Lampetra morii. AB - The metagenomic analysis and 16S rDNA sequencing method were used to investigate the bacterial community in the intestines of Lampetra morii. The bacterial community structure in L. morii intestine was relatively simple. Eight different operational taxonomic units were observed. Chitinophagaceae_unclassified (26.5 %) and Aeromonas spp. (69.6 %) were detected as dominant members at the genus level. The non-dominant genera were as follows: Acinetobacter spp. (1.4 %), Candidatus Bacilloplasma (2.5 %), Enterobacteria spp. (1.5 %), Shewanella spp. (0.04 %), Vibrio spp. (0.09 %), and Yersinia spp. (1.8 %). The Shannon-Wiener (H) and Simpson (1-D) indexes were 0.782339 and 0.5546, respectively. The rarefaction curve representing the bacterial community richness and Shannon-Wiener curve representing the bacterial community diversity reached asymptote, which indicated that the sequence depth were sufficient to represent the majority of species richness and bacterial community diversity. The number of Aeromonas in lamprey intestine was two times higher after stimulation by lipopolysaccharide than PBS. This study provides data for understanding the bacterial community harboured in lamprey intestines and exploring potential key intestinal symbiotic bacteria essential for the L. morii immune response. PMID- 27180096 TI - Lysobacter cavernae sp. nov., a novel bacterium isolated from a cave sample. AB - A Gram-staining negative, aerobic, rod-shaped bacterium, designated YIM C01544(T), was isolated from a soil sample collected from Sigangli Cave, Yunnan province, South-West China. The strain was able to grow over a range of temperatures (4-30 degrees C), pH (6.0-10.0) and NaCl concentration (0-2 %, w/v). Comparative 16S rRNA gene sequence analysis revealed that strain YIM C01544(T) should be a member of the genus Lysobacter. The strain is closely related to Lysobacter niastensis GH41-7(T) (97.6 %), Lysobacter soli DCY21(T) (97.5 %), Lysobacter enzymogenes DSM 2043(T) (97.3 %), Lysobacter antibioticus DSM 2044(T) (97.1 %) and Lysobacter panacisoli CJ29(T) (97.1 %). The genomic DNA relatedness values (<47 %) as indicated by DNA-DNA hybridization studies were below the threshold limit for characterization of new bacterial species. The chemotaxonomic features of the new isolate include diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, two unidentified phospholipids and two unidentified polar lipids as its characteristic polar lipids and Q-8 as the only quinone. The major fatty acids detected were iso-C15:0 and iso-C17:1 omega9c. The DNA G + C content of the strain was determined to be 64.9 mol %. Based on the data from phenotypic, chemotaxonomic and molecular studies, strain YIM C01544(T) merits recognition as novel species in the genus Lysobacter for which the name Lysobacter cavernae sp. nov. is proposed. The type strain of Lysobacter cavernae is YIM C01544(T) (= KCTC 42875(T) = DSM 101561(T) = CPCC 100816(T)). PMID- 27180097 TI - Thalassospira australica sp. nov. isolated from sea water. AB - Two Gram-negative, non-pigmented, motile bacteria were isolated from a sea water sample collected at St. Kilda Beach, Port Philip Bay, Victoria, Australia. The two strains were found to grow between 4 and 40 degrees C, pH 5-10 and tolerate up to 10 % NaCl. A phylogenetic study, based on a 16S rRNA gene sequence analysis indicated that strains NP 3b2(T) and H 94 belong to the genus Thalassospira. The sequence similarity of the 16S rRNA gene between the two new isolates is 99.8 % and between these strains and all validly named Thalassospira species was found to be in the range of 95-99.4 %. The DNA-DNA relatedness between the two strains was found to be 80.2 %, while relatedness with other validly named species of the genus Thalassospira was between 53 and 65 %. The average nucleotide identity (ANI) and the in silico genome-to-genome distance (GGD) between the two bacteria and T. profundimaris WP0211(T), T. xiamenensis M-5(T), 'T. permensis' NBRC 106175(T) and T. lucentensis QMT2(T) was 76-82 % and 21-25 %, respectively. The results of phylogenetic and genomic analysis, together with physiological and biochemical properties, indicated that the two strains represent a new species of the genus Thalassospira. Based on these data, a new species, Thalassospira australica, is proposed with strain NP 3b2(T) (=KMM 6365(T) = JCM 31222(T)) as the type strain. PMID- 27180098 TI - Beet western yellows virus infects the carnivorous plant Nepenthes mirabilis. AB - Although poleroviruses are known to infect a broad range of higher plants, carnivorous plants have not yet been reported as hosts. Here, we describe the first polerovirus naturally infecting the pitcher plant Nepenthes mirabilis. The virus was identified through bioinformatic analysis of NGS transcriptome data. The complete viral genome sequence was assembled from overlapping PCR fragments and shown to share 91.1 % nucleotide sequence identity with the US isolate of beet western yellows virus (BWYV). Further analysis of other N. mirabilis plants revealed the presence of additional BWYV isolates differing by several insertion/deletion mutations in ORF5. PMID- 27180099 TI - Hepatitis C virus and its protein NS4B activate the cancer-related STAT3 pathway via the endoplasmic reticulum overload response. AB - Oxidative stress induces the activation of signal transducer and activator of transcription 3 (STAT3), which plays an important role in hepatocellular carcinoma (HCC). We have previously reported that hepatitis C virus (HCV) and its protein NS4B induce the production of reactive oxygen species (ROS) via the endoplasmic reticulum overload response (EOR) in human hepatocytes. Here, we found that NS4B and HCV induce STAT3 activation and stimulate the expression of cancer-related STAT3 target genes, including VEGF, c-myc, MMP-9 and Mcl-1, by EOR in human hepatocytes. Moreover, the cancer-related STAT3 pathway activated by NS4B and HCV via EOR were found to promote human hepatocyte viability. Taken together, these findings revealed that HCV NS4B might contribute to HCC by activating the EOR-mediated cancer-related STAT3 pathway, and this could provide novel insights into HCV-induced HCC. PMID- 27180101 TI - Dual-Component Intramedullary Implant Versus Kirschner Wire for Proximal Interphalangeal Joint Fusion: A Randomized Controlled Clinical Trial. AB - We undertook a multicenter, parallel treatment arm, randomized controlled trial to compare the outcomes after surgery for the treatment of lesser digital hammertoe using either a Kirschner wire or a 2-piece intramedullary, stainless steel implant for fixation of the proximal interphalangeal joint. Our primary aim was to compare the incidence of arthrodesis and complications, and our secondary aim was to compare the subjective foot-related outcomes measured using the Bristol Foot Score and the Foot Function Index, stratified by fixation group. We hypothesized that the use of the dual-component implant would result in greater patient satisfaction, a greater incidence of radiographic arthrodesis, and fewer complications after hammertoe repair. The overall mean age of the participants was 58.72 +/- 13.48 (range 18 to 84) years, their mean body mass index was 30.14 +/- 6.55 (range 20.7 to 46.98) kg/m(2), and no statistically significant differences in the demographic variables were present between the treatment groups at baseline or during the follow-up period. Of the 91 participants, 46 (50.55%) were randomly allocated to the Kirschner wire group and 45 (49.45%) to the intramedullary implant group. No statistically significant differences were observed between the 2 fixation groups in the incidence of complications; however, the 2-piece intramedullary implant group was associated with a greater mean Bristol Foot Score and Foot Function Index score and a greater incidence of fusion. PMID- 27180102 TI - Previous induced abortion among young women seeking abortion-related care in Kenya: a cross-sectional analysis. AB - BACKGROUND: Unsafe abortion is a leading cause of death among young women aged 10 24 years in sub-Saharan Africa. Although having multiple induced abortions may exacerbate the risk for poor health outcomes, there has been minimal research on young women in this region who have multiple induced abortions. The objective of this study was therefore to assess the prevalence and correlates of reporting a previous induced abortion among young females aged 12-24 years seeking abortion related care in Kenya. METHODS: We used data on 1,378 young women aged 12-24 years who presented for abortion-related care in 246 health facilities in a nationwide survey conducted in 2012. Socio-demographic characteristics, reproductive and clinical histories, and physical examination assessment data were collected from women during a one-month data collection period using an abortion case capture form. RESULTS: Nine percent (n = 98) of young women reported a previous induced abortion prior to the index pregnancy for which they were receiving care. Statistically significant differences by previous history of induced abortion were observed for area of residence, religion and occupation at bivariate level. Urban dwellers and unemployed/other young women were more likely to report a previous induced abortion. A greater proportion of young women reporting a previous induced abortion stated that they were using a contraceptive method at the time of the index pregnancy (47 %) compared with those reporting no previous induced abortion (23 %). Not surprisingly, a greater proportion of young women reporting a previous induced abortion (82 %) reported their index pregnancy as unintended (not wanted at all or mistimed) compared with women reporting no previous induced abortion (64 %). CONCLUSIONS: Our study results show that about one in every ten young women seeking abortion-related care in Kenya reports a previous induced abortion. Comprehensive post-abortion care services targeting young women are needed. In particular, post-abortion care service providers must ensure that young clients receive contraceptive counseling and effective pregnancy prevention methods before discharge from the health care facility to prevent unintended pregnancies that may result in subsequent induced abortions. PMID- 27180103 TI - beta-glucan attenuated scopolamine induced cognitive impairment via hippocampal acetylcholinesterase inhibition in rats. AB - beta-glucan (polysaccharide) rich diet has been reported to enhance cognition in humans but the mechanism remained elusive. Keeping this in mind, the present study was designed to investigate the interaction of beta-glucan with central cholinergic system. Briefly, in-silico analysis revealed promising interactions of beta-glucan with the catalytic residues of acetylcholinesterase (AChE) enzyme. In line with this outcome, the in vitro assay (Ellman's method) also exhibited inhibition of AChE by beta-glucan (IC50=0.68+/-0.08MUg/ul). Furthermore, the in vivo study (Morris water maze) showed significant dose dependent reversal of the amnesic effect of scopolamine (2mg/kg i.p.) by beta-glucan treatment (5, 25, 50 and 100mg/kg, i.p.). Finally, the hippocampi of aforementioned treated animals also revealed dose dependent inhibition of AChE enzyme. Hence, it can be deduced that beta-glucan possesses potential to enhance central cholinergic tone via inhibiting AChE enzyme. In conclusion, the present study provides mechanistic insight to the cognition enhancing potential of beta-glucan. Keeping in mind its dietary use and abundance in nature, it can be considered as economic therapeutic option against cognitive ailments associated with decline in cholinergic neurotransmission. PMID- 27180104 TI - A novel method to promote behavioral improvement and enhance mitochondrial function following an embolic stroke. AB - Tissue plasminogen activator (tPA) is the only FDA-approved treatment for stroke; tPA increases cerebral reperfusion, blood flow and improved behavior. Novel transcranial laser therapy (TLT) also enhances cerebral blood flow and activates mitochondrial function. Using the rabbit small clot embolic stroke model (RSCEM), we studied the effects of continuous wave TLT (7.5mW/cm(2)) alone or in combination with standardized intravenous (IV) tPA (3.3mg/kg) applied 1h post embolization on 3 endpoints: 1) behavioral function measured 2 days [effective stroke dose (P50 in mg) producing neurological deficits in 50% of embolized rabbits], 2) intracerebral hemorrhage (ICH) rate, and 3) cortical adenosine-5' triphosphate (ATP) content was measured 6h following embolization. TLT and tPA significantly (p<0.05) increased P50 values by 95% and 56% (p<0.05), respectively over control. TLT-tPA increased P50 by 136% over control (p<0.05). Embolization reduced cortical ATP content by 39%; decreases that were attenuated by either TLT or tPA treatment (p<0.05). TLT-tPA further enhanced cortical ATP levels 22% above that measured in naive control. TLT and tPA both effectively and safely, without affecting ICH rate, improved behavioral outcome in embolized rabbits; and there was a trend (p>0.05) for the TLT-tPA combination to further increase P50. TLT and tPA both attenuated stroke-induced ATP deficits, and the combination of tPA and TLT produced an additive effect on ATP levels. This study demonstrates that the combination of TLT-tPA enhances ATP production, and suggests that tPA-induced reperfusion in combination with TLT neuroprotection therapy may optimally protect viable cells in the cortex measured using ATP levels as a marker. PMID- 27180105 TI - Long noncoding RNAs: Novel molecules in cardiovascular biology, disease and regeneration. AB - Remarkable breakthroughs made in genomic technologies have facilitated the discovery of thousands of novel transcripts that do not template protein synthesis. Numerous RNAs termed as long noncoding RNAs (lncRNAs) generated from this pervasive transcription function vividly in gene regulatory networks and a variety of biological and cellular processes. Here, we make a brief description of the known and putative functions of lncRNAs in cardiovascular biology and disease. The association between lncRNAs and stem cells mediated cardiomyocytes differentiation and neovascularization is discussed then. It will provide a new clue for further studies on these novel molecules in cardiovascular disease and bring bright prospects for their future applications in cardiac regenerative medicine. PMID- 27180106 TI - Anxiolytic-like effects of leptin on fixed interval responding. AB - Leptin has been shown to affect energy homeostasis, learning and memory, and some models of anxiolytic action. However, leptin has produced inconsistent results in previous non-operant behavioural tests of anxiety. Here, we test the anxiolytic potential of leptin in an operant paradigm that has produced positive results across all classes of anxiolytic so far tested. Rats were tested in the Fixed Interval 60 Seconds (FI60) task following administration of 0/0.5/1.0mg/kg (i.p.) leptin or an active anxiolytic control of 5mg/kg (i.p.) chlordiazepoxide (CDP). By the end of the 14days of testing in the FI60 task, 0.5mg/kg leptin released suppressed responding in a manner similar to CDP, and 1.0mg/kg leptin produced a relative depression in responding, a similar outcome pattern to previously tested 5HT-agonist anxiolytics. This suggests that leptin behaves similarly to established serotonergic anxiolytics such as buspirone and fluoxetine; with the delay in development of effect during testing, and the inverted-U dose-response curve explaining the inconsistent behaviour of leptin in behavioural tests of anxiety, as this type of pattern is common to serotonergic anxiolytics. PMID- 27180107 TI - Racial differences in the relationship between rate of nicotine metabolism and nicotine intake from cigarette smoking. AB - Rate of nicotine metabolism has been identified as an important factor influencing nicotine intake and can be estimated using the nicotine metabolite ratio (NMR), a validated biomarker of CYP2A6 enzyme activity. Individuals who metabolize nicotine faster (higher NMR) may alter their smoking behavior to titrate their nicotine intake in order to maintain similar levels of nicotine in the body compared to slower nicotine metabolizers. There are known racial differences in the rate of nicotine metabolism with African Americans on average having a slower rate of nicotine metabolism compared to Whites. The goal of this study was to determine if there are racial differences in the relationship between rate of nicotine metabolism and measures of nicotine intake assessed using multiple biomarkers of nicotine and tobacco smoke exposure. Using secondary analyses of the screening data collected in a recently completed clinical trial, treatment-seeking African American and White daily smokers (10 or more cigarettes per day) were grouped into NMR quartiles so that the races could be compared at the same NMR, even though the distribution of NMR within race differed. The results indicated that rate of nicotine metabolism was a more important factor influencing nicotine intake in White smokers. Specifically, Whites were more likely to titrate their nicotine intake based on the rate at which they metabolize nicotine. However, this relationship was not found in African Americans. Overall there was a greater step-down, linear type relationship between NMR groups and cotinine or cotinine/cigarette in African Americans, which is consistent with the idea that differences in blood cotinine levels between the African American NMR groups were primarily due to differences in CYP2A6 enzyme activity without titration of nicotine intake among faster nicotine metabolizers. PMID- 27180108 TI - Use of arbuscular mycorrhizal fungi to improve the drought tolerance of Cupressus atlantica G. AB - In this study, we investigated whether indigenous arbuscular mycorrhizal (AM) fungi could improve the tolerance of Cupressus atlantica against water deficit. We tested a gradient of watering regime spanning from 90% to 25% of soil retention capacity of water on mycorhized and non-mycorhized seedlings in pot cultures with sterilized and non-sterilized soils. Our result showed a positive impact of AM fungi on shoot height, stem diameter and biomass as well as on the growth rate. We also observed that inoculation with AM fungi significantly improved uptake of minerals by C. atlantica in both sterilized and non-sterilized soils independently of water regimes. We found that mycorhized plants maintained higher relative water content (RWC) and water potential compared with non mycorhized plants that were subjected to drought-stress regimes (50% and 25% of soil retention capacity). The contents of proline and of soluble sugars showed that their concentrations decreased in non-mycorhized plants subjected to DS. Superoxide dismutase (SOD) and catalase (CAT) activities also decreased in non mycorhized plants submitted to DS compared to mycorhized plants. The same pattern was observed by measuring peroxidase (POD) enzyme activity. The results demonstrated that AM fungal inoculation promoted the growth and tolerance of C. atlantica against DS in pot cultures. Therefore, mycorrhizal inoculation could be a potential solution for the conservation and reestablishment of C. atlantica in its natural ecosystem. PMID- 27180109 TI - Non-functional genes repaired at the RNA level. AB - Genomes and genes continuously evolve. Gene sequences undergo substitutions, deletions or nucleotide insertions; mobile genetic elements invade genomes and interleave in genes; chromosomes break, even within genes, and pieces reseal in reshuffled order. To maintain functional gene products and assure an organism's survival, two principal strategies are used - either repair of the gene itself or of its product. I will introduce common types of gene aberrations and how gene function is restored secondarily, and then focus on systematically fragmented genes found in a poorly studied protist group, the diplonemids. Expression of their broken genes involves restitching of pieces at the RNA-level, and substantial RNA editing, to compensate for point mutations. I will conclude with thoughts on how such a grotesquely unorthodox system may have evolved, and why this group of organisms persists and thrives since tens of millions of years. PMID- 27180110 TI - Meiotic recombination mechanisms. AB - Meiosis is a specialized cell division at the origin of the haploid cells that eventually develop into the gametes. It therefore lies at the heart of Mendelian heredity. Recombination and redistribution of the homologous chromosomes arising during meiosis constitute an important source of genetic diversity, conferring to meiosis a particularly important place in the evolution and the diversification of the species. Our understanding of the molecular mechanisms governing meiotic recombination has considerably progressed these last decades, benefiting from complementary approaches led on various model species. An overview of these mechanisms will be provided as well as a discussion on the implications of these recent discoveries. PMID- 27180100 TI - Biology-inspired microphysiological system approaches to solve the prediction dilemma of substance testing. AB - The recent advent of microphysiological systems - microfluidic biomimetic devices that aspire to emulate the biology of human tissues, organs and circulation in vitro - is envisaged to enable a global paradigm shift in drug development. An extraordinary US governmental initiative and various dedicated research programs in Europe and Asia have led recently to the first cutting-edge achievements of human single-organ and multi-organ engineering based on microphysiological systems. The expectation is that test systems established on this basis would model various disease stages, and predict toxicity, immunogenicity, ADME profiles and treatment efficacy prior to clinical testing. Consequently, this technology could significantly affect the way drug substances are developed in the future. Furthermore, microphysiological system-based assays may revolutionize our current global programs of prioritization of hazard characterization for any new substances to be used, for example, in agriculture, food, ecosystems or cosmetics, thus, replacing laboratory animal models used currently. Thirty-six experts from academia, industry and regulatory bodies present here the results of an intensive workshop (held in June 2015, Berlin, Germany). They review the status quo of microphysiological systems available today against industry needs, and assess the broad variety of approaches with fit-for-purpose potential in the drug development cycle. Feasible technical solutions to reach the next levels of human biology in vitro are proposed. Furthermore, key organ-on-a-chip case studies, as well as various national and international programs are highlighted. Finally, a roadmap into the future is outlined, to allow for more predictive and regulatory-accepted substance testing on a global scale. PMID- 27180111 TI - MCPIP1 RNase Is Aberrantly Distributed in Psoriatic Epidermis and Rapidly Induced by IL-17A. AB - ZC3H12A, which encodes the RNase monocyte chemotactic protein-induced protein 1 (MCPIP1), is up-regulated in psoriatic skin and reduced to normal levels after clinical treatments with anti-IL-17A/IL-17R neutralizing antibodies. In IL-17A stimulated keratinocytes, MCPIP1 is rapidly increased at the transcript and protein levels. Also, IL-17A was found to be the main inducer of ZC3H12A expression in keratinocytes treated with supernatants derived from a Streptococcus pyogenes-activated psoriatic ex vivo model based on the co-culture of psoriatic cutaneous lymphocyte-associated antigen (CLA(+)) T cells and lesional epidermal cells. Moreover, MCPIP1 was aberrantly distributed in the suprabasal layers of psoriatic epidermis. In psoriatic samples, IL-17A-stimulated epidermal cell suspensions showed an increased MCPIP1 expression, especially in the mid-differentiated cellular compartment. The knockdown of ZC3H12A showed that this RNase participates in the regulation of the mRNAs present in suprabasal differentiated keratinocytes. Furthermore, JAK/STAT3 inhibition prevented the IL 17A-dependent induction of MCPIP1. In the mouse model of imiquimod-induced psoriasis, Zc3h12a expression was abrogated in Il17ra(-/-) mice. These results support the notion that IL-17A-mediated induction of MCPIP1 is involved in the regulation of local altered gene expression in suprabasal epidermal layers in psoriasis. PMID- 27180113 TI - The importance of the microbiome in epidemiologic research. AB - PURPOSE: The human microbiome is the community of microorganisms that live on and in the body. Currently, most applications of microbiome analysis derive from the perspective of discovery and characterization. The completion of the NIH Human Microbiome and the European MetaHIT projects will change the focus to studying the role of the microbiome on human health and disease. METHODS: Recent developments in technology and bioinformatics have afforded an opportunity to explore more fully the importance of community structure, detection of pathogens, and community interactions. The current state of microbiome research in terms of effect size, power calculations, how stratification on community classes can increase this power, and the importance of study design and power in reproducibility is reviewed. RESULTS: Work is needed to characterize microbiome development, ecological stability, and variation. Development and implementation of variance stabilization techniques should replace rarefaction of data, which reduces study power, in future research. CONCLUSIONS: Epidemiologists have most of the tools necessary to explore the relationship between the microbiome and human health. Further development of tools for large-scale multivariate data sets will be helpful. Applying the methods of epidemiology will be critical in translating research results to preventive interventions and population health. PMID- 27180112 TI - Intricacies of assessing the human microbiome in epidemiologic studies. AB - PURPOSE: In the past decade, remarkable relationships have been documented between dysbiosis of the human microbiota and adverse health outcomes. This review seeks to highlight some of the challenges and pitfalls that may be encountered during all stages of microbiota research, from study design and sample collection, to nucleic acid extraction and sequencing, and bioinformatic and statistical analysis. METHODS: Literature focused on human microbiota research was reviewed and summarized. RESULTS: Although most studies have focused on surveying the composition of the microbiota, fewer have explored the causal roles of these bacteria, archaea, viruses, and fungi in affecting disease states. Microbiome research is in its relatively early years and many aspects remain challenging, including the complexity and personalized aspects of microbial communities, the influence of exogenous and often confounding factors, the need to apply fundamental principles of ecology and epidemiology, the necessity for new software tools, and the rapidly evolving genomic, technological, and analytical landscapes. CONCLUSIONS: Incorporating human microbiome research in large epidemiologic studies will soon help us unravel the intricate relationships that we have with our microbial partners and provide interventional opportunities to improve human health. PMID- 27180115 TI - Epidemiology and the microbiome. PMID- 27180114 TI - Self-reported herpes zoster, pain, and health care seeking in the Health and Retirement Study: implications for interpretation of health care-based studies. AB - PURPOSE: To describe self-reported herpes zoster (HZ) and explore factors that could impact interpretation of results from health care-based HZ studies. METHODS: We performed logistic regression using data from the 2008 Health and Retirement Study (HRS) to evaluate risk factors for having a history of HZ and experiencing severe HZ pain, and predictors for seeking health care for HZ. RESULTS: Among 14,564 respondents aged >=55 years, women were more likely than men to report a history of HZ (15.7% vs. 11.6%, P < .01). Blacks (6.4% vs. 14.7% in whites, P < .01) and respondents with less than a high school diploma (12.2% vs.14.2% in respondents with at least a high school diploma, P = .01) were less likely to report a history of HZ. Women, blacks, Hispanics, and those with less than a high school diploma were more likely to report severe HZ pain. Most (91.1%) respondents sought health care for HZ; Hispanics (64.2% vs. 92.1% in whites, P < .001) and those with recurrent HZ were less likely to seek health care for HZ, whereas those with severe pain were more likely (95.4% vs. 87.9% in those without severe pain, P < .01). CONCLUSIONS: HRS provides a new platform for studies of HZ, one which allowed us to uncover issues that warrant particular attention when interpreting results of health care-based studies. PMID- 27180116 TI - Endocrinopathies, Bone Health, and Insulin Resistance in Patients with Fanconi Anemia after Hematopoietic Cell Transplantation. AB - A number of endocrinopathies have been described after hematopoietic cell transplantation (HCT), but data are limited in patients with Fanconi anemia (FA). We report several endocrine-based disorders in a cohort of 44 patients with FA after HCT compared with both 74 patients who received HCT for hematologic malignancies and with 275 healthy controls. Endocrinopathies assessed included hypothyroidism, hypogonadism, short stature, dyslipidemia, insulin resistance, abnormalities in body composition, and bone health. Most (86%) patients with FA had at least 1 endocrinopathy, with 11% having 3 or more. Hypothyroidism was seen in 57%, hypogonadism in 27%, short stature in 50%, and reduced total body and lumbar spine bone mineral density (BMD) (height adjusted Z-score < -1) in 57% and 21%, respectively. Vitamin D deficiency was seen in 71%. Short stature was associated with younger age at HCT and gonadal failure was associated with older age at HCT. Insulin resistance was associated with increased percent fat mass and increased android/gynoid ratio by dual energy X-ray absorptiometry. Hypothyroidism, short stature, and reduced total body BMD were more prevalent in patients with FA compared with patients with hematologic malignancies. We recommend an assessment before transplantation and close follow-up afterwards to ensure proper clinical management. Future studies should continue to explore the impact of HCT on endocrinopathies in FA patients. PMID- 27180117 TI - Lack of association of plasma gamma prime (gamma') fibrinogen with incident cardiovascular disease. AB - INTRODUCTION: The association of gamma prime (gamma') fibrinogen; a fibrinogen gamma chain variant generated via alternative mRNA processing, with cardiovascular disease (CVD) remains equivocal. We prospectively examine the association of plasma gamma' fibrinogen with the incidence of multiple cardiovascular disease (CVD) endpoints, independent of established CVD risk factors and total fibrinogen. MATERIALS AND METHODS: We measured plasma gamma' fibrinogen on plasma samples collected in 1992-1993 from adults >=65years (n=3219) enrolled in the Cardiovascular Health Study, who were followed through 2013 for incident CVD events. RESULTS AND CONCLUSIONS: In multivariable Cox models adjusted for traditional CVD risk factors and total fibrinogen, the hazard ratio per 1 standard deviation (10.7mg/dl) increment of gamma' fibrinogen was 1.02 (95%CI: 0.95-1.10) for coronary heart disease; 0.88 (0.77-1.00) for ischemic stroke; 1.07 (0.87-1.32) for peripheral artery disease; 1.00 (0.92-1.08) for heart failure and 1.01 (0.92-1.10) for CVD mortality. Likewise, we failed to show a statistically significant association of gamma'/total fibrinogen ratio with any CVD endpoint. These results suggest that among the elderly, gamma' fibrinogen does not add much to CVD prediction beyond traditional risk factors and total fibrinogen level. PMID- 27180119 TI - Need for State Licensure. PMID- 27180118 TI - Evaluation of the technical performance of three different commercial digital breast tomosynthesis systems in the clinical environment. AB - The aim of this work was to research and evaluate the performance of three different digital breast tomosynthesis (DBT) systems in the clinical environment (Siemens Mammomat Inspiration, Hologic Selenia Dimensions, and Fujifilm Amulet Innovality). The characterization included the study of the detector, the automatic exposure control, and the resolution of DBT projections and reconstructed planes. The modulation transfer function (MTF) of the DBT projections was measured with a 1mm thick steel edge, showing a strong anisotropy (30-40% lower MTF0.5 frequencies in the tube travel direction). The in-plane MTF0.5, measured with a 25MUm tungsten wire, ranges from 1.3 to 1.8lp/mm in the tube-travel direction and between 2.4 and 3.7lp/mm in the chest wall-nipple. In the latter direction, the MTF peak shift is more emphasized for large angular range systems (2.0 versus 1.0lp/mm). In-depth resolution of the planes, via the full width at half maximum (FWHM) from the point spread function of a 25MUm tungsten wire, is not only influenced by angular range and yields 1.3-4.6mm among systems. The artifact spread function from 1mm diameter tungsten beads depends mainly on angular range, yielding two tendencies whether large (FWHM is 4.5mm) or small (FWHM is 10mm) angular range is used. DBT delivers per scan a mean glandular dose between 1.4 and 2.7mGy for a 45mm thick polymethyl methacrylate (PMMA) block. In conclusion, we have identified and analysed specific metrics that can be used for quality assurance of DBT systems. PMID- 27180120 TI - Effect of age on expression of spermatogonial markers in bovine testis and isolated cells. AB - Spermatogonial stem cells (SSC) are the most undifferentiated germ cell present in adult male testes and, it is responsible to maintain the spermatogenesis. Age has a negative effect over stem cell, but the aging effect on SSC is not elucidated for bovine. The present study aim to evaluate the effect of age on the expression of undifferentiated spermatogonial markers in testis and in enriched testicular cells from prepubertal calves and adult bulls. In this matter, testicular parenchyma from calves (3-5 months) (n=5) and bulls with 3 years of age (n=5) were minced and, isolated cells were obtained after two enzymatic digestions. Differential platting was performed for two hours onto BSA coated dish. Cell viability was assessed by Trypan Blue solution exclusion method and testicular cells enriched for SSC was evaluated by expression of specific molecular markers by qRT-PCR (POU5F1, GDNF, CXCR4, UCHL1, ST3GAL, SELP, ICAM1 and ITGA6) and flow cytometry (GFRA1, CXCR4 and ITGA6). CXCR4 and UCHL1 expression was evaluated in fixated testes by immunohistochemistry. We observed that age just affected the expression of selective genes [SELP (Fold Change=5.61; p=0.0023) and UCHL1 (Fold Change=4.98; p=0.0127)]. By flow cytometry, age affected only the proportion of ITGA6+ cells (P<0.001), which was higher in prepubertal calves when compared to adult bulls. In situ, we observed an effect of age on the number of UCHL1+ (p=0.0006) and CXCR4+ (p=0.0139) cells per seminiferous tubule. At conclusion, age affects gene expression and the population of cells expressing specific spermatogonial markers in the bovine testis. PMID- 27180121 TI - Autophagy proteins are modulated in the liver and hypothalamus of the offspring of mice with diet-induced obesity. AB - Nutritional excess during pregnancy and lactation has a negative impact on offspring phenotype. In adulthood, obesity and lipid overload represent factors that compromise autophagy, a process of lysosomal degradation. Despite knowledge of the impact of obesity on autophagy, changes in offspring of obese dams have yet to be investigated. In this study, we tested the hypothesis that maternal obesity induced by a high fat diet (HFD) modulates autophagy proteins in the hypothalamus and liver of the offspring of mice. At birth (d0), offspring of obese dams (HFD-O) showed an increase in p62 protein and a decrease in LC3-II, but only in the liver. After weaning (d18), the offspring of HFD-O animals showed impairment of autophagy markers in both tissues compared to control offspring (SC O). Between day 18 and day 42, both groups received a control diet and we observed that the protein content of p62 remained increased in the livers of the HFD-O offspring. However, after 82days, we did not find any modulation in offspring autophagy proteins. On the other hand, when the offspring of obese dams that received an HFD from day 42 until day 82 (OH-H) were compared with the offspring from the controls that only received an HFD in adulthood (OC-H), we saw impairment in autophagy proteins in both tissues. In conclusion, this study describes that HFD-O offspring showed early impairment of autophagy proteins. Although the molecular mechanisms have not been explored, it is possible that changes in autophagy markers could be associated with metabolic disturbances of offspring. PMID- 27180122 TI - Predictive Validity of the American College of Cardiology/American Heart Association Pooled Cohort Equations in Predicting All-Cause and Cardiovascular Disease-Specific Mortality in a National Prospective Cohort Study of Adults in the United States. AB - The predictive validity of the Pooled Cohort risk (PCR) equations for cardiovascular disease (CVD)-specific and all-cause mortality among a national sample of US adults has yet to be evaluated, which was this study's purpose. Data from the 1999-2010 National Health and Nutrition Examination Survey were used, with participants followed up through December 31, 2011, to ascertain mortality status via the National Death Index probabilistic algorithm. The analyzed sample included 11,171 CVD-free adults (40-79 years of age). The 10-year risk of a first atherosclerotic cardiovascular disease (ASCVD) event was determined from the PCR equations. For the entire sample encompassing 849,202 person-months, we found an incidence rate of 1.00 (95% CI, 0.93-1.07) all-cause deaths per 1000 person months and an incidence rate of 0.15 (95% CI, 0.12-0.17) CVD-specific deaths per 1000 person-months. The unweighted median follow-up duration was 72 months. For nearly all analyses (unadjusted and adjusted models with ASCVD expressed as a continuous variable as well as dichotomized at 7.5% and 20%), the ASCVD risk score was significantly associated with all-cause and CVD-specific mortality (P<.05). In the adjusted model, the increased all-cause mortality risk ranged from 47% to 77% based on an ASCVD risk of 20% or higher and 7.5% or higher, respectively. Those with an ASCVD score of 7.5% or higher had a 3-fold increased risk of CVD-specific mortality. The 10-year predicted risk of a first ASCVD event via the PCR equations was associated with all-cause and CVD-specific mortality among those free of CVD at baseline. In this American adult sample, the PCR equations provide evidence of predictive validity. PMID- 27180123 TI - The Pooled Cohort Equations for Predicting Risk of Myocardial Infarction and Stroke: Validated in Representative Natural History Populations. PMID- 27180124 TI - Comparative study of late rectal toxicity in prostate cancer patients treated with low-dose-rate brachytherapy: With or without supplemental external beam radiotherapy. AB - PURPOSE: Supplemental external beam radiation therapy (sEBRT) is often prescribed in men undergoing low-dose-rate (LDR) brachytherapy. A population of patients was analyzed to assess the effect of sEBRT on late rectal toxicity. It was hypothesized that sEBRT + LDR would be associated with a higher risk of late rectal toxicity. METHODS AND MATERIALS: This retrospective cohort study examined LDR brachytherapy patients, treated with or without sEBRT, with a minimum of 5 year followup. Longitudinal assessments were evaluated using the computerized patient record system. The Kaplan-Meier method was used for analysis. RESULTS: Median followup was 7.5 years for 245 patients from 2004 to 2007. sEBRT was administered to 33.5%. Followup beyond 5 years was available for 89%. Overall rates of Grade >=2 and >=3 rectal toxicities were 6.9% and 2.9%, respectively. The risk of Grade >=2 rectal toxicity was 2.8-fold higher for patients receiving sEBRT (95% confidence interval: 1.1-7.2; p = 0.02). The risk of Grade >=3 rectal toxicity was 11.9-fold higher for patients who received sEBRT (1.5-97.4, 95% confidence interval; p = 0.003). Six of seven patients with a Grade >=3 rectal toxicity received sEBRT, including one who required an abdominoperineal resection. Median post-LDR D90, V150, V200, and R100 values were 103.3%, 59.4%, 30.1%, and 0.5 cc. CONCLUSIONS: In a cohort of LDR brachytherapy patients with high rates of followup, sEBRT + LDR was associated with significantly higher risk of Grade >=2 and >=3 late rectal toxicity. This analysis supports previous findings and maintains concern about the supplemental use of external beam radiation therapy with LDR brachytherapy while its benefit for tumor control has yet to be prospectively validated. PMID- 27180125 TI - Radiation safety of receptive anal intercourse with prostate cancer patients treated with low-dose-rate brachytherapy. AB - PURPOSE: Prostate low-dose-rate (LDR) brachytherapy involves implantation of radioactive seeds permanently into the prostate gland. During receptive anal intercourse, the penis of the partner may come in close proximity to the implanted prostate gland. We estimate the potential intrarectal dose rates and suggest guidance on radiation precautions. METHODS AND MATERIALS: One hundred two patients were included in the study. After implantation, with patients under anesthesia in the dorsal lithotomy position, a new set of ultrasound (US) images and a CT scan were obtained. The images were fused, radioactive seeds and US probe locations were determined on the CT, and prostate, bladder, and rectal contours were drawn on the US. Dose rates (cGy/h) were calculated for the portion of the US probe spanning the prostate for several dose-volume histogram parameters. RESULTS: Twenty patients were treated with (125)I and 82 patients with (103)Pd. Average dose rates at Day 0 to the portion of the US probe spanning the prostate were 2.1 +/- 1.3 cGy/h and 2.5 +/- 0.8 cGy/h for patients treated with (125)I and (103)Pd, respectively. After 60 days, average calculated probe dose drops to 1.0 +/- 0.6 cGy/h and 0.2 +/- 0.1 cGy/h for (125)I and (103)Pd, respectively. CONCLUSIONS: During the immediate weeks after prostate seed implant, the estimated intrarectal dose rates are higher in (103)Pd compared to (125)I. As (103)Pd decays faster than (125)I, 2 months after the implant, radiation exposure from (103)Pd becomes lower than (125)I. Receptive anal intercourse time should be kept as low as possible during 2 and 6 months after low-dose-rate brachytherapy of the prostate with (103)Pd and (125)I, respectively. PMID- 27180126 TI - Intraoperative ultrasound-based planning can effectively replace postoperative CT based planning for high-dose-rate brachytherapy for prostate cancer. AB - PURPOSE: Ultrasound (US)-based planning for high-dose-rate brachytherapy allows prostate patients to be implanted, imaged, planned, and treated without changing position. This is advantageous with respect to accuracy and efficiency of treatment but is only valuable if plan quality relative to CT is maintained. This study evaluates any dosimetric impact of changing from CT- to US-based planning. METHODS AND MATERIALS: Thirty patients each were randomly selected from CT planned and US-planned cohorts. All received single fraction high-dose-rate brachytherapy (15 Gy) followed by 37.5 Gy in 15 fractions external beam radiation therapy. Prostate V90, V100, V150, V200, D90, and the dose homogeneity index were compared. For the rectum, Dmax, D0.5cc, D1cc, V10, V50, and V80 were examined. For the urethra, only Dmax and D10 were considered. RESULTS: US plans had smaller 200% hot spots, although the dose homogeneity index for both was 0.7 +/- 0.1. On average, plans using either modality satisfied planning goals. Although several parameters were significantly different between the two modalities (p < 0.05), the absolute differences were small. Of greatest, clinical relevance was the difference in frequency with which upper dose goals were exceeded. The prostate V200 goal was exceeded in 53% of CT-planned cases, but only 20% of those planned with US. The urethral D10 goal was never exceeded using US but was exceeded in 13% of CT cases. CONCLUSIONS: US planning results in plans that, clinically, are dosimetrically equivalent to CT-based planning. Upper dosimetric goals are, however, exceeded less often with US than with CT. PMID- 27180127 TI - Evaluating the utility of "3D Slicer" as a fast and independent tool to assess intrafractional organ dose variations in gynecological brachytherapy. AB - PURPOSE: To demonstrate the utility of "3D Slicer" for easy treatment verification by comparing dose-volume histograms (DVHs) calculated on pretreatment and posttreatment images. METHODS AND MATERIALS: Thirty cervical cancer patients were CT scanned twice: first for treatment planning and a second time after the dose delivery. The initial plan was manually duplicated on the posttreatment image set in Flexiplan treatment planning system, and DVH parameters were calculated. Pretreatment and posttreatment images, organ structures, and plan data were exported from the treatment planning system to 3D Slicer to validate DVH parameter calculation with 3D Slicer. The gamma analysis was used to compare Flexiplan and 3D Slicer DVHs. Posttreatment images were rigidly fused on the initial CT to automatically transfer the data of the pretreatment plan onto the posttreatment images. DVH parameters were calculated in 3D Slicer for both image sets, and their relative variations were compared. RESULTS: In calculating DVH parameter variations, no significant differences were observed between Flexiplan and 3D Slicer. Where the registration accuracy was better than 0.03, they returned similar results for D2 cm(3) of bladder, rectum, and sigmoid. Mean and standard deviation of DVH parameters were calculated on pretreatment and posttreatment images for several organs; both the manually duplicated plan and the automatically registered plan in SlicerRT returned comparable relative variations of these parameters. For 88% of the organs, more than 95% of the DVH dose bins passed the gamma analysis. CONCLUSIONS: We tested an automated DVH assessment method with an imaging freeware, 3D Slicer, for use in image-guided adaptive brachytherapy. SlicerRT is a viable verification tool to report and detect DVH variations between different contoured images series. PMID- 27180128 TI - Implications of staged reconstruction and adjuvant brachytherapy in the treatment of recurrent soft tissue sarcoma. AB - PURPOSE: Prior studies illustrated a reduction in wound complications with the use of staged reconstruction (SR) and negative pressure wound therapy when treating soft tissue sarcoma (STS) with surgical resection followed by high-dose rate adjuvant brachytherapy. The purpose of this study is to compare the outcomes of SR and immediate reconstruction (IR) brachytherapy in recurrent STS. METHODS AND MATERIALS: A retrospective review of 40 patients with recurrent STS of the local extremity and trunk treated with resection followed by adjuvant brachytherapy alone. Margin status was defined as positive (SM(+)) if there was microscopic involvement (R1) or <=1 mm margin and negative (SM(-)) if >1 mm margin was obtained. SR and IR were compared regarding toxicity, local control, and limb preservation. RESULTS: Median followup was 27 months. When comparing the SR (n = 22) and IR (n = 18) cohorts, there was a significantly lower final SM(+) rate in SR (32% vs. 83%, p < 0.01). A 2-year local control benefit seen with SR (80% vs. 34%; p = 0.012) and a final SM(-) (81% vs. 39%; p = 0.023). SR was associated with less toxicity on multivariate analysis, including a 90% decrease in persistent edema, an 80% decrease in wound dehiscence, and a 94% decrease in nonhealing wounds, when compared to IR. Ten of 31 (32%) extremity cases required eventual amputation from either chronic wound complications (n = 4) or local recurrence (n = 6). SR predicted for a benefit in 2-year limb preservation (88% vs. 50%; p = 0.008). CONCLUSION: In our series, the treatment with SR brachytherapy resulted in less morbidity and an improved final SM(-) rate. This technique translated to an improvement in both local control and limb preservation of recurrent STS. PMID- 27180129 TI - Image-guided adaptive brachytherapy in cervical cancer: Patterns of relapse by brachytherapy planning parameters. AB - PURPOSE: Cervical cancer patients with a bulky high-risk clinical target volume (HR-CTV) get the largest benefit of dose escalation in terms of local control. However, the expected survival benefit could be lessened by a higher metastatic risk. We examined the patterns of relapse according to major prognostic factors: the HR-CTV volume and to the D90 HR-CTV. METHODS AND MATERIALS: The clinical records of patients treated with pulsed-dose-rate image-guided adaptive brachytherapy after concurrent pelvic chemoradiation were reviewed. All patients had an optimal workup before treatment comprising a 18-fluorodeoxyglucose positron emission tomography/computed tomography and a para-aortic lymph node dissection. Patients with initial extrapelvic disease were excluded. RESULTS: A total of 109 patients fulfilled inclusion criteria. Median followup was 39 months. An HR-CTV volume >=40 cm(3) was associated with a poorer local failure free survival. There was a strong inverse correlation between the HR-CTV volume and the D90 of the HR-CTV (correlation coefficient r = -0.696; p < 0.001) with increasing HR-CTV volume being associated with a decreasing D90 HR-CTV. A D90 HR CTV <85 Gy and an HR-CTV volume >=40 cm(3) were significant univariate factors for experiencing nonlocal failure (p = 0.002 and 0.035, respectively), even after exclusion of local relapses. CONCLUSION: A lower ability to reach the target D90 HR-CTV planning and an HR-CTV volume >= 40 cm(3) correlated with a high propensity of relapsing at distance, these factors being interrelated. Next step of treatment personalization should design strategies integrating this risk, which is now the main cause of failure. PMID- 27180130 TI - MRI-guided brachytherapy in locally advanced cervical cancer: Small bowel [Formula: see text] and [Formula: see text] are not predictive of late morbidity. AB - PURPOSE: To establish dose-volume effect correlations for late small bowel (SB) toxicities in patients treated for locally advanced cervical cancer with concomitant chemoradiation followed by pulsed-dose rate MRI-guided adaptive brachytherapy. METHODS AND MATERIALS: Patients treated with curative intent and followed prospectively were included. The SB loops closed to CTV were delineated, but no specific dose constraint was applied. The dosimetric data, converted in 2 Gy equivalent, were confronted with the occurrence of late morbidity assessed using the CTC-AE 3.0. Dose-effect relationships were assessed using mean-dose comparisons, log-rank tests on event-free periods, and probit analyses. RESULTS: A total of 115 patients with a median followup of 35.5 months were included. Highest grade per patient was: Grades 0 for 17, 1 for 75, 2 for 20, and 3 for 3. The mean [Formula: see text] and [Formula: see text] were, respectively, 68.7 +/- 13.6 Gy and 85.8 +/- 33.1 Gy and did not differ according to event severity (p = 0.47 and p = 0.52), even when comparing Grades 0-1 vs. 2-4 events (68.0 +/- 12.4 vs. 71.4 +/- 17.7 Gy; p = 0.38 and 83.7 +/- 26.4 vs. 94.5 +/- 51.9 Gy; p = 0.33). Log-rank tests were performed after splitting the cohort according to four [Formula: see text] levels: >80 Gy, 70-79 Gy, 60-70 Gy, and <60 Gy. No difference was observed for Grades 1-4, Grades 2-4, or Grades 3-4 (p = 0.21-0.52). Probit analyses showed no correlation between the dosimetric parameters and probability of Grades 1-4, 2-4, or 3-4 events (p = 0.19-0.48). CONCLUSION: No significant dose-volume effect relationships were demonstrated between the [Formula: see text] and [Formula: see text] and the probability of late SB morbidity. These parameters should not limit the pulsed-dose rate brachytherapy optimization process. PMID- 27180131 TI - Prospective study of direct radiation exposure measurements for family members living with patients with prostate (125)I seed implantation: Evidence of radiation safety. AB - PURPOSE: To broaden the current understanding of radiation exposure and risk and to provide concrete evidence of radiation safety related to (125)I seed implantation. METHODS AND MATERIALS: Direct radiation exposure measurements were obtained from dosimeters provided to 25 patients who underwent (125)I seed implantation, along with their family members. The estimated lifetime exposure dose and the precaution time for holding children near the patient's chest were calculated in two study periods. RESULTS: During the first and second study period, the mean estimated lifetime exposure doses were, respectively, 7.61 (range: 0.45, 20.21) mSv and 6.84 (range: 0.41, 19.20) mSv for patients, and 0.19 (range: 0.02, 0.54) mSv and 0.25 (range: 0.04, 1.00) mSv for family members. The mean ratios of first and second period measurements were 1.05 (range: 0.44, 3.18) for patients and 1.82 (range: 0.21, 7.04) for family members. The corresponding absolute differences between first and second period measurements were -0.77 (range: -11.40, 7.63) mSv and 0.06 (range: -0.26, 0.79) mSv, respectively. Assuming a dose limit of 1 mSv, the precaution times for holding a child every day of the first and second periods were 250.9 (range: 71.3, 849.4) min and 275.2 (range: 75.0, 883.4) min, respectively. Assuming a dose limit of 0.5 mSv, the corresponding precaution times were 179.0 (range: 35.6, 811.5) min and 178.9 (range: 37.5, 1131.8) min, respectively. CONCLUSIONS: Our study demonstrated low radiation exposures to family members of patients undergoing (125)I prostate implantation. It was clear that (125)I seed implantation did not pose a threat to the safety of family members. PMID- 27180132 TI - Emotional profile of female rats showing binge eating behavior. PMID- 27180133 TI - Simulated acute central Mycoplasma infections in rats induce fever, anorexia, body mass stunting and lethargy but spare memory. AB - Despite the documented post-infectious neurological complications of a central nervous system (CNS) Mycoplasma infection in humans, very few studies have investigated the acute inflammatory responses and sickness behaviours induced by CNS Mycoplasma infections. We therefore determined the effect of acute central administration of fibroblast-stimulating lipopeptide-1 (FSL-1), derived from Mycoplasma salivarium, and FAM-20 from a more pathogenic species, namely Mycoplasma pneumoniae, on behavioural and inflammatory responses in rats. Male Sprague-Dawley rats had radiotransmitters implanted, intra-abdominally, to measure body temperature and cage activity continuously. After recovery from surgery, rats were conditioned in a fear conditioning task and then immediately received an intra-cisterna magna (i.c.m.) injection of either: (1) FSL-1 (10 or 100MUg/5MUl) or its vehicle (phosphate-buffered saline, 5MUl), or (2) FAM-20 (10 or 100MUg/5MUl) or its vehicle (dimethyl sulfoxide, 5MUl). Body mass and food intake were measured daily. Memory was assessed seven days after injection using fear conditioning tests. A single, i.c.m. injection of either FSL-1 or FAM-20 induced profound, dose-dependent fever, anorexia, lethargy and body mass stunting in rats. Moreover, rats that received an i.c.m. injection of 100MUg/5MUl FAM-20 had a significant increase in the concentration of IL-1beta in both the hypothalamus and the hippocampus for ~27h after injection. Seven days after FSL-1 or FAM-20 injection, when body mass of rats still was stunted, they maintained their memory for fear of the context and for fear of the tone, despite the increase in hippocampal IL-1beta concentration after FAM-20 administration. Thus, acute simulated CNS Mycoplasma infections caused pronounced sickness responses and brain inflammation in rats, but spared fear memory. PMID- 27180134 TI - Uric acid excretion predicts increased aggression in urban adolescents. AB - Elevated levels of uric acid have been linked with impulsive and disinhibited behavior in clinical and community populations of adults, but no studies have examined uric acid in relation to adolescent aggression. This study examined the prospective role of uric acid in aggressive behavior among urban, low income adolescents, and whether this relationship varies by gender. A total of 84 adolescents (M age 13.36years; 50% male; 95% African American) self-reported on their physical aggression at baseline and 1.5years later. At baseline, the youth also completed a 12-h (overnight) urine collection at home which was used to measure uric acid excretion. After adjusting for baseline aggression and age, greater uric acid excretion predicted more frequent aggressive behavior at follow up, with no significant gender differences. The results suggest that lowering uric acid levels may help reduce youth aggression. PMID- 27180135 TI - On the incompatibilities of interaction scales and processes with focus on the work of adhesion. AB - The mutual compatibility of Hamaker constants, solubility parameters or cohesive energy densities (CED) and surface/interface tensions are evaluated. It is shown that the partial contributions (dispersive, Lifshitz-van der Waals, dipolar induction, dipolar orientation, polar, acid, base and hydrogen bond) to Hamaker constants, solubility parameters or cohesive energy densities and surface/interface tensions are mutually inconsistent. The published reference data for a single set of liquids is moreover shown to be exceedingly scattered; making the parallel use of these scales challenging. Reference processes designed for bringing two and three phases into mutual contact are conflicting. The two phase processes within Hamaker and exchange energy density (EED) frameworks agree, but the three-phase models differ. As a free-standing parameter the EED is however comparable. The two-phase adhesion process is shown to be incompatible with the other contact processes and the three-phase adhesion process is opposite to them. One reason for this controversy is the different averaging of interfacial properties. While interfacial Hamaker constants and solubility parameters or cohesive energy densities are geometric averages of corresponding intervening phase properties, this practice is replaced by the work of adhesion being geometrically averaged as works of cohesion. As a result, there exist three conflicting models for the adhesion process: the Dupre work of adhesion, the Girifalco-Good geometric averaged works of cohesion and Fowkes reduced interfacial or interphasial tension process. None of these agree with the commonly accepted standard Hamaker contact processes and they should be replaced with the compatible extended work of adhesion process originally suggested by Dupre. The models offered for the conversion of Hamaker constants and solubility parameters or cohesive energy densities to surface tensions involve conversion factors and equilibrium distances between planes of molecules in liquids. The equilibrium distance for different close packings derived from molar liquid volumes are about 2-5 times larger than the cutoff distances obtained from simulations. Using volumetric equilibrium distances, the conversion factors for dispersive, polar and total Hamaker constant and solubility parameter or cohesive energy densities to surface tensions become nearly equal but they are different for each liquid. PMID- 27180136 TI - Mobile apps and metabolic health. PMID- 27180137 TI - Early recognition of diabetic peripheral neuropathy and the need for one-stop microvascular assessment. PMID- 27180138 TI - Nutrient labelling: legislating against too much information? PMID- 27180139 TI - A novel nonsense GPSM2 mutation in a Yemeni family underlying Chudley-McCullough syndrome. AB - Mutations in the G Protein Signaling Modulator 2 (GPSM2) cause the autosomal recessive disorder Chudley-McCullough syndrome (CMS), which is characterized by profound congenital sensorineural hearing loss with various abnormalities in the brain. This phenotypic combination is attributed to the role played by GPSM2 in the establishment of planar polarity and spindle orientation during asymmetric cell divisions. Here we present two brothers from a Yemeni family who were diagnosed clinically with CMS then tested for GPSM2 mutations using Sanger sequencing. Consequent to sequencing, in silico tools (such as CADD) were utilized to assess functional consequences. Molecular analysis revealed a previously unreported homozygous mutation in GPSM2 in both brothers (c.1055C > A) leading to a truncating protein change; (p.Ser352*). This mutation is predicted to abolish all four GoLoco domains in GPSM2 and this explains the bioinformatic prediction for this mutation to be functionally damaging. Full clinical and molecular accounts of the novel mutation are provided in this paper. PMID- 27180140 TI - Chromosome Xq28 duplication encompassing MECP2: Clinical and molecular analysis of 16 new patients from 10 families in China. AB - INTRODUCTION: Chromosome Xq28 duplications encompassing methyl-CpG-binding protein 2 gene (MECP2) are observed most in males with a severe neurodevelopmental disorder associated with hypotonia, spasticity, severe learning disability, delayed psychomotor development, and recurrent pulmonary infections. Most female carriers are asymptomatic due to extremely or completely skewed X-inactivation. METHODS: A retrospective clinical and molecular study was conducted to examine 16 patients and two fetuses from 10 families who were identified among patients with Xq28 duplications who presented at genetic clinics. RESULTS: Of all 16 patients, 10 had a family history. Only one patient was female. All of the patients had no relevant pre-natal history. All of the patients exhibited severe psychomotor developmental delay, infantile hypotonia and recurrent infections. Some of the patients exhibited cardiac abnormalities, gastrointestinal mobility problems, hydrocele of tunica vaginalis, cryptorchidism, and autistic phenotypes. Additionally, neonatal kidney calculus, premature closure of the fontanel and pulmonary sequestration were found in the patients. Duplication sizes in these patients range from 0.21 to 14.391 Mb (most were smaller than 1 Mb), and all the duplications included host cell factor C1 (HCFC1), interleukin-1 receptor-associated kinase 1 (IRAK1), and MECP2. Bioinformatics analysis revealed that approximately half of the distal breakpoints were located within the low-copy repeats (LCRs), which may be involved in the recombination. The two fetuses were found to be healthy in the prenatal diagnosis. CONCLUSION: This is the first large cohort of patients with MECP2 duplication syndrome, including a female, reported in China. Interestingly, neonatal kidney calculus, premature closure of the fontanel and pulmonary sequestration were first reported in this syndrome. However, it was difficult to distinguish if these patients represented unique cases or if these phenotypes can be considered as part of the syndrome. The correlation between the infrequent phenotypes and duplications/genes in the duplication region needs further systematic delineation. In conclusion, our study suggested that it is important to emphasize molecular genetic analysis in patients with developmental delay/intellectual disability and recurrent infections and that it is especially important for familial female carriers to accept prenatal diagnosis. PMID- 27180142 TI - Neurologic foundations of spinal cord fusion (GEMINI). AB - Cephalosomatic anastomosis has been carried out in both monkeys and mice with preservation of brain function. Nonetheless the spinal cord was not reconstructed, leaving the animals unable to move voluntarily. Here we review the details of the GEMINI spinal cord fusion protocol, which aims at restoring electrophysiologic conduction across an acutely transected spinal cord. The existence of the cortico-truncoreticulo-propriospinal pathway, a little-known anatomic entity, is described, and its importance concerning spinal cord fusion emphasized. The use of fusogens and electrical stimulation as adjuvants for nerve fusion is addressed. The possibility of achieving cephalosomatic anastomosis in humans has become reality in principle. PMID- 27180141 TI - Circulating cell-free nucleic acids and platelets as a liquid biopsy in the provision of personalized therapy for lung cancer patients. AB - Lung cancer is the predominant cause of cancer-related mortality in the world. The majority of patients present with locally advanced or metastatic non-small cell lung cancer (NSCLC). Treatment for NSCLC is evolving from the use of cytotoxic chemotherapy to personalized treatment based on molecular alterations. Unfortunately, the quality of the available tumor biopsy and/or cytology material is not always adequate to perform the necessary molecular testing, which has prompted the search for alternatives. This review examines the use of circulating cell-free nucleic acids (cfNA), consisting of both circulating cell-free (tumoral) DNA (cfDNA-ctDNA) and RNA (cfRNA), as a liquid biopsy in lung cancer. The development of sensitive and accurate techniques such as Next-Generation Sequencing (NGS); Beads, Emulsion, Amplification, and Magnetics (BEAMing); and Digital PCR (dPCR), have made it possible to detect the specific genetic alterations (e.g. EGFR mutations, MET amplifications, and ALK and ROS1 translocations) for which targeted therapies are already available. Moreover, the ability to detect and quantify these tumor mutations has enabled the follow-up of tumor dynamics in real time. Liquid biopsy offers opportunities to detect resistance mechanisms, such as the EGFR T790M mutation in the case of EGFR TKI use, at an early stage. Several studies have already established the predictive and prognostic value of measuring ctNA concentration in the blood. To conclude, using ctNA analysis as a liquid biopsy has many advantages and allows for a variety of clinical and investigational applications. PMID- 27180144 TI - Air pollution and blood lipid markers levels: Estimating short and long-term effects on elderly hypertension inpatients complicated with or without type 2 diabetes. AB - With the development of society and the economy, many Chinese cities are shrouded in pollution haze for much of the year. Scientific studies have identified various adverse effects of air pollutants on human beings. However, the relationships between air pollution and blood lipid levels are still unclear. The objective of this study is to explore the short and long-term effects of air pollution on eight blood lipid markers among elderly hypertension inpatients complicated with or without type 2 diabetes (T2D). Blood lipid markers which met the pre-established inclusion criteria were exported from the medical record system. Air pollution data were acquired from the official environmental protection website. Associations between the air quality index and the blood lipid indexes were analyzed by one-way ANOVA and further Bonferroni correction. In an exposure time of 7 days or longer, blood lipid markers were somewhat affected by poor air quality. However, the results could not predict whether atherosclerosis would be promoted or inhibited by poorer air condition. Changes of blood lipid markers of hypertension inpatients with or without T2D were not completely the same, but no blood lipid markers had an opposite trend between the two populations. The air quality index was associated with changes to blood lipid markers to some extent in a population of hypertension inpatients with or without T2D. Further studies are needed to investigate the potential mechanism by which air pollutants induce blood lipids changes. PMID- 27180145 TI - SAPIEN XT Valve-in-valve Implantation in Stenotic Valve. PMID- 27180143 TI - SOD2 and the Mitochondrial UPR: Partners Regulating Cellular Phenotypic Transitions. AB - ATP and reactive oxygen species (ROS) are signaling molecules that control cellular function and phenotype. Mitochondria produce both ATP and ROS. Since the electrons needed to generate either ATP or ROS originate from NADH/FADH2, the mechanism through which electrons flow towards oxygen determines yields and whether ATP or ROS prevails. Alterations in the electron flow impact cells dramatically, such as by supporting specialization (which requires high ATP) or imposing dedifferentiation. High ROS, facilitated by enzymes such as superoxide dismutase 2 (SOD2) that enhance mitochondrial hydrogen peroxide (mtH2O2), are normally linked to dedifferentiation of somatic cells. Here we propose that combined high mtH2O2 and mitochondrial unfolded protein response (UPR(mt)) activation are essential for somatic dedifferentiation programs and the acquisition of stem-like properties in reparative processes and disease. PMID- 27180146 TI - Mild hypothermia attenuate kidney injury in canines with oleic acid-induced acute respiratory distress syndrome. AB - BACKGROUND: Hypothermia may attenuate ventilator induced-lung injury in acute respiratory distress syndrome (ARDS). However, the impact of hypothermia on extra pulmonary organ injury in ARDS remains unclear. The purpose of this study was to investigate whether hypothermia affects extra-pulmonary organ injury in a canine ARDS model induced by oleic acid. OBJECTIVES: Twelve anesthetized canines with oleic acid-induced ARDS were randomly divided (n=6 per group) into a hypothermia group (core temperature of 33+/-1 degrees C, HT group) and a normothermia group (core temperature of 38+/-1 degrees C, NT group) and treated for four hours. The liver, small intestine and kidney were assessed by evaluating biochemical parameters, plasma and tissue cytokine levels, and tissue histopathological injury scores. RESULTS: The HT group showed a lower plateau pressure, lung elastance and pulmonary vascular resistance. Hypothermia was associated with lower oxygen consumption (138.4+/-55.0mlmin(-1)vs. 72.0+/-11.2mlmin(-1), P<0.05) and higher oxygen saturation of mixed venous blood (62.8%+/-8.0% vs. 77.5%+/ 10.1%, P<0.05). Both groups had similar levels of tumour necrosis factor-alpha in the plasma and extra-pulmonary organ, however, plasma interleukin-10 (97.1+/ 25.0pgml(-1)vs. 131.4+/-27.0pgml(-1), P<0.05) was higher in the HT group. Further, the animals in the HT group had a lower levels of plasma creatinine (54.6+/-19.1UL(-1)vs. 29.1+/-8.0UL(-1), P<0.05), and lower renal histopathological injury scores [4.0(3.5;7.0) vs. 1.5(0.8;3.0), P<0.05]. Hypothermia did not affect the histopathological injury of the liver and small intestine. CONCLUSIONS: Short-term mild hypothermia can reduce lung elastance and pulmonary vascular resistance, increase the systemic anti-inflammatory response and attenuate kidney histopathological injury in a canine ARDS model induced by oleic acid. PMID- 27180147 TI - mHealth information for migrants: an e-health intervention for internal migrants in Vietnam. AB - BACKGROUND: Socio-economic development in Vietnam has resulted in increased internal migration particularly among young women seeking employment opportunities in cities. Vietnamese female migrants who enter new environments often encounter the loss or neglect of their right to access sexual and reproductive health services. To address this, a mobile health (mHealth) intervention model was implemented over 12 months (2013-2014) in a factory in the Long Bien industrial zone of Hanoi, Vietnam. METHODS: The intervention provided sexual and reproductive health services for female migrants through text messaging, information booklets accompanied maps, and free counseling via a hotline. To evaluate the impact of the intervention, pre- and post-intervention data were collected to measure changes in women's knowledge and practices related to sexual and reproductive health. Qualitative data in the form of personal interviews were also collected. The sample size for the baseline survey was 411 women, and for the post-intervention survey it was 482 women (the intervention involved an open cohort). The majority of women were unmarried and under the age of 25. RESULTS: Results indicate that there was high uptake of the intervention services and that most women found the services important and useful. In addition, there was evidence that the intervention (1) increased women's knowledge of sexual and reproductive health (e.g., proper use of condoms, identification of high-risk behaviors such as having unprotected sex), and (2) fostered improved practices related to sexual and reproductive health (e.g., increased gynecological check-ups and use of condoms). CONCLUSIONS: The study demonstrated the feasibility of implementing a multi-faceted intervention for migrant women working in an industrial zone in Hanoi, Vietnam as well as its successful uptake and some early positive effects. This can be used to inform future design and implementation of mHealth/eHealth intervention models for migrant and other vulnerable/hard to reach population. PMID- 27180148 TI - Mechanical Effects of Heat Exposure From a Bipolar Radiofrequency Probe on Suture Under Simulated Arthroscopic Conditions. AB - PURPOSE: To determine conditions for the safe use of radiofrequency (RF) tissue ablation probes that avoid damaging suture material. METHODS: Four sutures made of 3 different materials commonly used in arthroscopic procedures were analyzed in a saline bath related to effects of RF-produced heat by proximity, duration, and intensity settings measuring burn-through time and ultimate load to failure. The parameters tested were electrode-to-suture distance, power setting, and the presence of tendon tissue or metallic anchor eyelets. Outcome variables were the burn-through time and the ultimate failure load of differently treated suture samples. RESULTS: Mean burn-through time for suture in direct contact with the RF probe ranged from 57.2 to 14.7 seconds for ultra-high-molecular-weight polyethylene (UHMWPE) sutures, 1.1 seconds for polydioxanone suture, and 0.8 seconds for polyethylene terephthalate suture. One of the UHMWPE sutures was capable of withstanding 3 seconds of direct contact with the RF probe without any compromise in tensile strength. No suture material tested had any mechanical change as long as the RF probe was kept 1 mm from the suture. CONCLUSIONS: Heat from RF tissue ablation probes can cause undetected damage. High-strength UHMWPE sutures were less sensitive to an RF treatment than polyester sutures. The use of different test substrates did not significantly influence the burn through time. CLINICAL RELEVANCE: Heat from RF probes can damage some suture material if direct contact is made even briefly. The use of RF devices may be safe for the suture when a distance between probe and suture of >1 mm is maintained. Suture made from UHMWPE may tolerate up to 3 seconds of RF probe contact and not sustain significant damage. Surgeons must use great care when using RF devices in the vicinity of suture placement. PMID- 27180149 TI - Humeral Avulsion of the Glenohumeral Ligaments: A Systematic Review. AB - PURPOSE: To analyze clinical outcomes, range of motion, rate of recurrence, and complications after procedures to manage shoulder instability in patients with humeral avulsion of the glenohumeral ligament (HAGL) lesions. METHODS: A systematic review of the literature according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines with a PRISMA checklist and algorithm was performed. A comprehensive search of PubMed, Medline, CINAHL, Cochrane, Embase, and Google Scholar databases using various combinations of the Keywords "shoulder," "HAGL," "treatment," "lesion," "dislocation," "instability," "clinical," "outcome," "Bankart" since inception of databases to 2015 was performed. All the investigators independently extracted the following data: demographics, types of lesions and associated injuries, treatment, outcome measurements, range of motion, recurrent instability, and complications. RESULTS: Eleven articles were included in which 42 shoulders with HAGL lesions were evaluated. Patients were assessed at a median follow-up period of 25.5 months, ranging from 12 to 54 months. The overall rate of recurrence was 0% (0 of 25) in case of surgery and 90% (9 of 10) in case of nonoperative treatment. The surgical approach was associated with lower rate of recurrence when compared with nonoperative treatment (odds ratio 0.05, 95% confidence interval 0.01 to 0.42, and P = .006). Only 2 papers reported loss of external rotation after surgery. No complications were reported after surgery. Complications after nonoperative treatment were not discussed. CONCLUSIONS: Recognizing HAGL lesions is important to manage patients with glenohumeral instability. Patients' complaints are often nonspecific. A high index of suspicion is required in patients with prior failed shoulder surgery. HAGL lesions are often associated with other shoulder lesions. Arthroscopic or open repairs of HAGL lesions are associated with good clinical outcomes and a lower rate of recurrence compared with nonoperative treatment. LEVEL OF EVIDENCE: Level IV, systematic review of Level IV studies. PMID- 27180150 TI - Congenital Glioblastoma multiforme and eruptive disseminated Spitz nevi. AB - BACKGROUND: Glioblastoma multiforme (GBM) is the deadliest malignant primary brain tumor in adults. GBM develops primarily in the cerebral hemispheres but can develop in other parts of the central nervous system. Its congenital variant is a very rare disease with few cases described in literature. CASE PRESENTATION: We describe the case of a patient with congenital GBM who developed eruptive disseminated Spitz nevi (EDSN) after chemotherapy. Few cases of EDSN have been described in literature and this rare clinical variant, which occurs predominantly in adults, is characterized by multiple Spitz nevi in the trunk, buttocks, elbows and knees. There is no satisfactory treatment for EDSN and the best therapeutic choice is considered the clinical observation of melanocytic lesions. CONCLUSION: We recommend a close follow-up of these patients with clinical observation, dermoscopy and reflectance confocal microscopy (RCM). However, we suggest a surgical excision of the lesions suspected of being malignant. PMID- 27180151 TI - Levonorgestrel intrauterine system for endometrial protection in women with breast cancer on adjuvant tamoxifen: A cochrane review summary. PMID- 27180152 TI - Stopping systemic menopausal hormone therapy: Why, when and how. PMID- 27180153 TI - Associations of androgens with health care utilization and costs in women Perspectives of a population-based cohort study. AB - OBJECTIVE: Despite associations between total testosterone (TT) concentrations and increased cardiometabolic risk, the impact of serum androgens on health care utilization and costs among women is unknown. METHODS: We used data from 1521 women in the population-based cohort Study of Health in Pomerania (SHIP) to investigate the associations of serum TT (measured by liquid chromatography tandem mass spectrometry), sex hormone-binding globulin (SHBG), and free testosterone (free T) with health care utilization and costs at baseline and five year follow-up (N=1210), implementing multivariable-adjusted econometric models. RESULTS: Cross-sectional analyses showed no association of TT, SHBG, or free T with hospitalization or total health costs (outpatient as well as inpatient costs). Prospective analyses revealed an inverse association of baseline SHBG with follow-up total health care costs (% change per standard deviation (SD): 26.2%, 95% confidence interval (CI): -42.2%; -8.9%) and inpatient costs (% change per SD: -26.5%%, 95% CI: -45.5%; -2.5%). Baseline free T was positively associated with total health care costs at the five-year follow-up (% change per SD: +37.7%, 95% CI: +4.6%; +81.4%). CONCLUSIONS: In this first cost analysis among women from the general population, we observed no association of androgen serum concentration with health care utilization and costs. However, baseline SHBG appeared to be inversely correlated and free T positively correlated with long-term health care costs. PMID- 27180154 TI - Factors associated to institutionalization and mortality over three years, in elderly people with a hip fracture-An observational study. AB - OBJECTIVE: To identify the factors associated to institutionalization and mortality in elderly patients with hip fractures (HF). DESIGN: Thirty-six months observational study. SETTING: A post-acute rehabilitation ward. PARTICIPANTS: subjects living in the community or in nursing-home, above the age of 65, with HF. MEASUREMENTS: The following were registered: comorbidity, intra-hospital complications, Barthel index, walking ability and Mini Mental State Examination, as well as blood samples upon admission and discharge. Destination upon discharge was recorded as well as mortality during hospital stay and over the three-year follow up. RESULTS: a total of 430 subjects were included in the study. Twenty three patients (5.3%) died during their stay in hospital and 152 (35.3%) during follow up after discharge. Forty-five patients (10.5%) were institutionalized upon discharge. In adjusted analysis, the factors that predict intra-hospital mortality are higher comorbidity (OR, 1.46; 95%CI, 1.06-2.01), and the number of complications (OR, 1.71; 95%CI, 1.16-2.64). Factors that predict mortality in the long term are age (HR 1.04; 95%CI, 1.01-1.06), comorbidity (HR 1.19, 95% CI, 1.09 1.30), the number of complications (HR 1.17, 95%CI, 1.05-1.31). The factors that predicted new institutionalization were age (OR 1.04, 95%CI, 0.98-1.09), living alone (OR 3.95, 95%CI, 1.38-11.3), and length of hospital stay (OR 1.02 95%CI, 1.00-1.03). CONCLUSIONS: Mortality 3 years after a hip fracture and institutionalization are associated to age, the loss of autonomy in walking, a worse cognitive status and living alone before the fracture. Identification of and, when possible, intervention upon these factors can improve care of elderly people with hip fractures. PMID- 27180155 TI - Aging and bone health in Singaporean Chinese pre-menopausal and postmenopausal women. AB - OBJECTIVE: The study evaluated relationships between menopausal statuses, hormone replacement therapy (HRT), body mass index (BMI), percent body fat (PBF), and exercise with osteoporosis and bone mineral density (BMD) in Singaporean women. STUDY DESIGN: This is a cross-sectional study. MAIN OUTCOME MEASURES: The spine BMD, and femoral neck BMD as well as the prevalence of osteoporosis are the main outcome measures studied. RESULTS: Age, BMI, PBF and exercise intensity were independently associated with spine and femoral neck BMD. Women with higher BMI and lower PBF had higher BMD and lower prevalence of osteoporosis. Postmenopausal women without HRT had lower BMD and higher prevalence of osteoporosis while those on HRT had similar BMD and prevalence of osteoporosis as premenopausal women. CONCLUSION: This study shows that BMI and PBF are powerful predictors of BMD. Osteoporosis is site-specific in the Singapore population, being higher in the femoral neck than in the lumbar spine. The bone status after menopause may not be worse than that dictated by age alone and both ERT and E/PRT could sustain the BMD to levels corresponding to those of women a decade younger. A strategy to improve bone health should include dieting and physical exercise program that focuses on selectively reducing fat mass and increasing lean mass. PMID- 27180156 TI - Obesity and osteoarthritis. AB - This paper provides an up-to-date review of obesity and lower limb osteoarthritis (OA). OA is a major global cause of disability, with the knee being the most frequently affected joint. There is a proven association between obesity and knee OA, and obesity is suggested to be the main modifiable risk factor. Obese patients (Body Mass Index, BMI, over 30kg/m(2)) are more likely to require total knee arthroplasty (TKA). The global prevalence of obesity has doubled since 1980; by 2025, 47% of UK men and 36% of women are forecast to be obese. This rising global burden is a key factor in the growing rise in the use of TKA. It is therefore important to appreciate the outcomes of surgery in patients with end stage OA and a high BMI. This review found that while OA is felt to contribute to weight gain, it is unclear whether TKA facilitates weight reduction. Surgery in obese patients is more technically challenging. This is reflected in the evidence, which suggests higher rates of short- to medium-term complications following TKA, including wound infection and medical complications, resulting in longer hospital stay, and potentially higher rates of malalignment, dislocation, and early revision. However, despite slower initial recovery and possibly lower functional scores and implant survival in the longer term, obese patients can still benefit from TKA in terms of improved function, quality of life and satisfaction. In conclusion, despite higher risks and more uncertain outcomes of surgery, higher BMI in itself should not be a contraindication to TKA; instead, each patient's individual circumstances should be considered. PMID- 27180157 TI - Sex differences in the association of physical function and cognitive function with life satisfaction in older age: The Rancho Bernardo Study. AB - OBJECTIVES: This study examines the cross-sectional associations of cognitive and physical function with life satisfaction in middle-class, community-dwelling adults aged 60 and older. STUDY DESIGN: Participants were 632 women and 410 men who had cognitive function tests (CFT) and physical function tasks (PFT) assessed at a clinic visit between 1988 and 1992, and who responded in 1992 to a mailed survey that included life satisfaction measures. Cognitive impairment was defined as <=24 on MMSE, >=132 on Trails B, <=12 on Category Fluency, <=13 on Buschke long-term recall, and <=7 on Heaton immediate recall. Physical impairment was defined as participants' self-reported difficulty (yes/no) in performing 10 physical functions. Multiple linear regression examined associations between life satisfaction and impairment on >=1 CFT or difficulty with >=1 PFT. MAIN OUTCOME MEASURES: The Satisfaction with Life Scale (SWLS; range:0-26) and Life Satisfaction Index-Z (LSI-Z; range:5-35). RESULTS: Participants' average age was 73.4 years (range=60-94). Categorically defined cognitive impairment was present in 40% of men and 47% of women. Additionally, 30% of men and 43% of women reported difficulty performing any PFT. Adjusting for age and impairment on >=1 CFT, difficulty performing >=1 PFT was associated with lower LSI-Z and SWLS scores in men (beta=-1.73, -1.26, respectively, p<0.05) and women (beta=-1.79, 1.93, respectively, p<0.01). However, impairment on >= 1 CFT was not associated with LSI-Z or SWLS score after adjusting for age and difficulty with >=1 PFT. CONCLUSIONS: Limited cognitive function was more common than limited physical function; however, limited physical function was more predictive of lower life satisfaction. Interventions to increase or maintain mobility among older adults may improve overall life satisfaction. PMID- 27180158 TI - Complementary health approaches for health and wellness in midlife and older US adults. AB - OBJECTIVES: To characterize the use of complementary health approaches (CHA) and examine the perceived benefits of using CHA by reason for use among midlife and older adults. STUDY DESIGN: Analysis of 2012 National Health Interview Survey data, a nationally representative US sample using cross-tabulations with design based F-tests and multiple logistic regression. The analytic sample included adults aged over 50 years (N=14,849). MAIN OUTCOME MEASURES: The proposed benefits of using CHA included: (1) better control over health, (2) reduced stress/relaxation, (3) better sleep, (4) feeling better emotionally, (5) coping with health problems, (6) improved health/feeling better, and (7) improved relationships. RESULTS: Overall, 31% of this sample of midlife and older US adults had used CHA in the past year. Among users, 15% had used CHA for treatment only, 40% for wellness only, and 45% for combined wellness and treatment. Herbs (60%), chiropractic (28%), massage (22%), and yoga (19%) were the most common CHA. Wellness-only and combined users had significantly higher odds of reporting that CHA conferred benefit compared with treatment-only users. CONCLUSIONS: CHA are used by nearly a third of midlife and older adults and are perceived to provide substantial benefit. Integrating CHA as part of a healthy lifestyle has the potential to contribute to healthy aging among midlife and older adults. PMID- 27180159 TI - Hot flushes and reproductive hormone levels during the menopausal transition. AB - INTRODUCTION: Evidence suggests that hot flushes are associated with fluctuating levels of oestradiol (E2) during menopause, as well as changes in the levels of follicle-stimulating hormone (FSH) and inhibin B. The relationship between hot flushes and anti-Mullerian hormone (AMH) is unknown. AIM: To examine specific hormone levels and ethnic differences in relation to hot flushes. METHODS: Data were drawn from 108 women aged 40-59 years. There were three groups of participants: European women in London, UK; Bangladeshi women in Sylhet, Bangladesh; and Bangladeshi women who had migrated to London as adults. Symptom information was collected via questionnaires. Serum blood samples were collected to detect inhibin B, AMH, FSH, and E2. RESULTS: AMH and FSH were significantly associated with the experience of hot flushes in the past 2 weeks. Inhibin B and E2 were not associated with hot flushes. Body mass index (BMI), ethnicity, and education level were associated with both the occurrence and the frequency hot flushes. Menopausal status was also associated with the frequency of hot flushes. CONCLUSION: Relationships between AMH, FSH and symptoms are indicative of women's progress through the menopausal transition. The influence of BMI and education suggest that lifestyle changes may contribute to the management of symptoms. This merits further research. PMID- 27180160 TI - Observational and mechanistic links between C-reactive protein and blood pressure in elderly women. AB - It is hypothesized that chronic systemic inflammation contributes to the age related decline in cardiovascular function. The aim of the present study was to combine an assessment of the relationship between the serum level of C-reactive protein (CRP) and systolic and diastolic blood pressure in 108 elderly women (65 and 70 years) with an in-vitro exploration of the effects of CRP on the proliferative and angiogenic potential of endothelial cells exposed to serum in elderly women. Based on the median CRP level in our population, LowCRP (CRP<1.3mg/L) and HighCRP (>1.3mg/L) groups were identified. Body mass index, waist circumference, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were significantly higher in the HighCRP group than in the LowCRP group (p<0.05). The influence of CRP on SBP and DBP remained significant after adjustments for BMI and use of antihypertensive medication (p<0.05). When adjusting for waist circumference the observed influence of CRP on SPB was attenuated (p=0.062). We next evaluated the ability to form capillary tubes (angiogenesis assay) and the proliferation rate of endothelial cells exposed to the sera of elderly women. Increased serum CRP levels were associated with an increased doubling time of endothelial cells (R(2)=0.39; p<0.05) and decreased capillary tube length (R(2)=0.30; p<0.05), indicating a reduction in the proliferation rate of endothelial cells and angiogenic potential. In conclusion, chronic inflammation influences blood pressure in elderly women and compromises endothelial cell function, thus contributing to the age-related decline in vascular health. PMID- 27180161 TI - Cardiovascular surveillance in breast cancer treatment: A more individualized approach is needed. AB - Newly developed treatment strategies for breast cancer have reduced mortality rates over the past decades. Patients with breast cancer represent a heterogeneous population. Differences in the severity of the disease require diverse treatment options. Women have distinct individual risk patterns for cardiovascular disease that may affect their susceptibility to cardiotoxicity during therapy. While breast cancer treatment is targeted more on tumor and patient characteristics, a tailored individual approach with early and late cardiosurveillance is not yet implemented in routine care. Newly available cardiac imaging techniques are better suited to the early detection of cardiotoxicity and should be used more often in those patients at highest risk, as the early intervention afforded will improve their quality of life and prognosis. PMID- 27180162 TI - Maintaining postreproductive health: A care pathway from the European Menopause and Andropause Society (EMAS). AB - This position statement from the European Menopause and Andropause Society (EMAS) provides a care pathway for the maintenance of women's health during and after the menopause. It is designed for use by all those involved in women's health. It covers assessment, screening for diseases in later life, treatment and follow-up. Strategies need to be optimised to maintain postreproductive health, in part because of increased longevity. They encompass optimising diet and lifestyle, menopausal hormone therapy and non-estrogen-based treatment options for climacteric symptoms and skeletal conservation, personalised to individual needs. PMID- 27180163 TI - Characteristics associated with initiation of hormone replacement therapy among Finnish women: A register-linkage study. AB - OBJECTIVE: To investigate which patient characteristics are associated with the initiation of hormone replacement therapy (HRT) in a cohort of Finnish women. STUDY DESIGN: Responses to postal questionnaires distributed to a nationwide, randomly selected cohort of women in 1998, 2000, 2003, 2005 and 2010 were analyzed. The cohort members were aged 40-44 years at the beginning of the study. Information on hormone replacement therapy was received from the national prescription register. Women who started taking HRT between January 1, 1999 and December 31, 2011 were included and previous users were excluded from the analysis. MAIN OUTCOME MEASURES: Initiation of HRT was the main outcome measure. The following explanatory factors for predicting the use of HRT were examined: sociodemographic factors, personality, health behavior, physiological and mental symptoms, chronic diseases and use of psychopharmaceuticals. The associations between starting HRT and the explanatory factors were analyzed with single predictor and multi-predictor logistic regression models. RESULTS: Factors predicting that a woman would start taking HRT were: living with a partner, weak sense of coherence, BMI less than 30kg/m(2), heavy or moderate alcohol use, symptoms of hyperactivity of the sympathetic nervous system, climacteric symptoms and use of psychopharmaceuticals. CONCLUSIONS: Women with a good sense of coherence can cope with climacteric symptoms without resorting to HRT. Clinicians need to bear in mind the burden of menopausal symptoms on a woman's personal and working life when HRT is being considered. PMID- 27180165 TI - Waist circumference percentiles for Singaporean children and adolescents aged 6 17 years. AB - AIM: Population-specific waist circumference (WC) percentiles are crucial for screening children at higher obesity-related metabolic risk. This study aimed to develop age- and gender-specific WC percentile curves for Singaporean children and adolescents. METHODS: 3029 participants (boys, 1506; girls, 1523) from different population strata of Singapore were recruited. Stature, weight and WC were measured and BMI calculated. Smoothed WC percentile curves and cut-offs for the 3rd, 5th, 10th, 25th, 50th, 75th, 85th, 90th, 95th, 97th were constructed using the Cole's LMS method. RESULTS: WC and BMI increased with age in both sexes and boys had higher WC than girls at every age. Comparison of 50th and 90th percentiles with other populations showed distinct difference in WC curve patterns and values of Singaporean children. CONCLUSIONS: We present the first working WC percentile curves and age- and gender-specific cut-offs of Singaporean children and adolescents. These cut-offs and curves can serve as valuable reference for screening and identify children at a higher metabolic risk, for international comparisons and to better understand secular trends in paediatric obesity. PMID- 27180164 TI - Identification of definitive serum biomarkers associated with disease activity in primary Sjogren's syndrome. AB - BACKGROUND: In this study, we sought to identify definitive biomarkers associated with disease activity in primary Sjogren's syndrome (pSS). METHODS: Serum protein concentrations in pSS patients and healthy controls (HCs) were comprehensively screened using high-throughput proteomic analysis, and differentially expressed proteins were extracted. Correlation between differentially expressed proteins and European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (ESSDAI) scores was analyzed and disease activity-associated biomarkers were identified. These biomarkers were validated by enzyme-linked immunosorbent assay (ELISA) in a separate pSS cohort. RESULTS: The serum concentrations of 1100 proteins were compared between 30 pSS patients and 30 HCs, with 82 differentially expressed proteins identified as pSS-associated proteins. Of these 82 proteins, 9 were identified as disease activity-associated biomarkers. These nine biomarkers underwent validation by ELISA in a separate pSS validation cohort (n = 58), with five proteins (CXCL13, TNF-R2, CD48, B-cell activating factor (BAFF), and PD-L2) subsequently being confirmed as candidate biomarkers. Of these five candidate biomarkers, CXCL13 exhibited the most significant correlation with the lymphadenopathy, glandular, and pulmonary domains of the ESSDAI. CXCL13, TNF-R2 and CD48 exhibited a positive correlation with the biological domain of the ESSDAI. TNF-R2 exhibited the most negative correlation with uptake in the submandibular gland on technetium 99m-pertechnetate salivary gland scintigraphy. CONCLUSIONS: Our approach successfully identified serum biomarkers associated with disease activity in pSS patients. These markers might be potential therapeutic targets in pSS patients. PMID- 27180166 TI - Sex-specific effects of early life stress on social interaction and prefrontal cortex dendritic morphology in young rats. AB - Early life stress has been linked to depression, anxiety, and behavior disorders in adolescence and adulthood. The medial prefrontal cortex (mPFC) is implicated in stress-related psychopathology, is a target for stress hormones, and mediates social behavior. The present study investigated sex differences in early-life stress effects on juvenile social interaction and adolescent mPFC dendritic morphology in rats using a maternal separation (MS) paradigm. Half of the rat pups of each sex were separated from their mother for 4h a day between postnatal days 2 and 21, while the other half remained with their mother in the animal facilities and were exposed to minimal handling. At postnatal day 25 (P25; juvenility), rats underwent a social interaction test with an age and sex matched conspecific. Distance from conspecific, approach and avoidance behaviors, nose-to nose contacts, and general locomotion were measured. Rats were euthanized at postnatal day 40 (P40; adolescence), and randomly selected infralimbic pyramidal neurons were filled with Lucifer yellow using iontophoretic microinjections, imaged in 3D, and then analyzed for dendritic arborization, spine density, and spine morphology. Early-life stress increased the latency to make nose-to-nose contact at P25 in females but not males. At P40, early-life stress increased infralimbic apical dendritic branch number and length and decreased thin spine density in stressed female rats. These results indicate that MS during the postnatal period influenced juvenile social behavior and mPFC dendritic arborization in a sex-specific manner. PMID- 27180167 TI - MK-801 and memantine act differently on short-term memory tested with different time-intervals in the Morris water maze test. AB - N-methyl-d-aspartate receptors (NMDARs) play a crucial role in spatial memory formation. In neuropharmacological studies their functioning strongly depends on testing conditions and the dosage of NMDAR antagonists. The aim of this study was to assess the immediate effects of NMDAR block by (+)MK-801 or memantine on short term allothetic memory. Memory was tested in a working memory version of the Morris water maze test. In our version of the test, rats underwent one day of training with 8 trials, and then three experimental days when rats were injected intraperitoneally with low- 5 (MeL), high - 20 (MeH) mg/kg memantine, 0.1mg/kg MK 801 or 1ml/kg saline (SAL) 30min before testing, for three consecutive days. On each experimental day there was just one acquisition and one test trial, with an inter-trial interval of 5 or 15min. During training the hidden platform was relocated after each trial and during the experiment after each day. The follow up effect was assessed on day 9. Intact rats improved their spatial memory across the one training day. With a 5min interval MeH rats had longer latency then all rats during retrieval. With a 15min interval the MeH rats presented worse working memory measured as retrieval minus acquisition trial for path than SAL and MeL and for latency than MeL rats. MK-801 rats had longer latency than SAL during retrieval. Thus, the high dose of memantine, contrary to low dose of MK-801 disrupts short-term memory independent on the time interval between acquisition and retrieval. This shows that short-term memory tested in a working memory version of water maze is sensitive to several parameters: i.e., NMDA receptor antagonist type, dosage and the time interval between learning and testing. PMID- 27180168 TI - Enhanced attention and impulsive action following NMDA receptor GluN2B-selective antagonist pretreatment. AB - NMDA GluN2B (NR2B) subtype selective antagonists are currently in clinical development for a variety of indications, including major depression. We previously reported the selective NMDA GluN2B antagonists Ro 63-1908 and traxoprodil, increase premature responding in a 5-choice serial reaction time task (5-CSRTT) suggesting an effect on impulsive action. The present studies extend these investigations to a Go-NoGo and delay discounting task, and the 5 CSRTT under test conditions of both regular (5s) and short (2-5s) multiple ITI (Intertrial interval). Dizocilpine was included for comparison. Both Ro 63-1908 (0.1-1mg/kg SC) and traxoprodil (0.3-3mg/kg SC) increased premature and perseverative responses in both 5-CSRT tasks and improved attention when tested under a short ITI test condition. Ro 63-1908 but not traxoprodil increased motor impulsivity (false alarms) in a Go-NoGo task. Dizocilpine (0.01-0.06mg/kg SC) affected both measures of motor impulsivity and marginally improved attention. In a delay discounting test of impulsive choice, both dizocilpine and Ro 63-1908 decreased impulsive choice (increased choice for the larger, delayed reward), while traxoprodil showed a similar trend. Motor stimulant effects were evident following Ro 63-1908, but not traxoprodil treatment - although no signs of motor stereotypy characteristic of dizocilpine (>0.1mg/kg) were noted. The findings of both NMDA GluN2B antagonists affecting measures of impulsive action and compulsive behavior may underpin emerging evidence to suggest glutamate signaling through the NMDA GluN2B receptor plays an important role in behavioural flexibility. The profiles between Ro 63-1908 and traxoprodil were not identical, perhaps suggesting differences between members of this drug class. PMID- 27180169 TI - Central role for NMDA receptors in redox mediated impairment of synaptic function during aging and Alzheimer's disease. AB - Increased human longevity has magnified the negative impact that aging can have on cognitive integrity of older individuals experiencing some decline in cognitive function. Approximately 30% of the elderly will have cognitive problems that influence their independence. Impaired executive function and memory performance are observed in normal aging and yet can be an early sign of a progressive cognitive impairment of Alzheimer's disease (AD), the most common form of dementia. Brain regions that are vulnerable to aging exhibit the earliest pathology of AD. Senescent synaptic function is observed as a shift in Ca2+ dependent synaptic plasticity and similar mechanisms are thought to contribute to the early cognitive deficits associated with AD. In the case of aging, intracellular redox state mediates a shift in Ca2+ regulation including N-methyl d-aspartate (NMDA) receptor hypofunction and increased Ca2+ release from intracellular stores to alter synaptic plasticity. AD can interact with these aging processes such that molecules linked to AD, beta-amyloid (Abeta) and mutated presenilin 1 (PS1), can also degrade NMDA receptor function, promote Ca2+ release from intracellular stores, and may increase oxidative stress. Thus, age is one of the most important predictors of AD and brain aging likely contributes to the onset of AD. The focus of this review article is to provide an update on mechanisms that contribute to the senescent synapse and possible interactions with AD-related molecules, with special emphasis on regulation of NMDA receptors. PMID- 27180170 TI - Relationships between County Health Rankings and child overweight and obesity prevalence: a serial cross-sectional analysis. AB - BACKGROUND: The County Health Rankings (CHR) system provides health rankings for U.S. counties. These factors may have utility for evaluating and predicting health outcomes. This study examined the association between CHR factors and the prevalence of child overweight/obesity (OWOB) in the state of Pennsylvania over 3 years. METHODS: The prevalence of childhood OWOB was obtained for all Pennsylvania school districts for the 2009-10 through 2011-12 school years. Correlational and inferential statistical analyses were used to examine the associations between the prevalence of OWOB in grades K-6 (OWOB1) and 7-12 (OWOB2) and z-score for the overall CHR Health Factors rank, as well as for individual predictive factors (Health Behaviors, Clinical Care, Social and Economic Factors and Physical Environment). RESULTS: Low to moderate correlations (0.29-0.43) were found between OWOB1 and CHR factors. Weaker and less consistent correlations were found for adolescents. There was a significantly higher prevalence of OWOB in counties with poorer CHR scores. CONCLUSIONS: County-level adult indicators of health are significantly associated with levels of child obesity. Future studies should examine the relationship between CHR and other health outcomes. PMID- 27180171 TI - The Experience of Counseling Among a Singaporean Elderly Population: A Qualitative Account of What Clients Report as Beneficial. AB - Adjustments that accompany ageing pose a challenge to the mental health of the elderly. Psychologically based counseling has been documented in Western societies as an appropriate intervention for elderly persons with depressive episodes. There is however very little research documenting how Asian elderly populations experience and benefit from counseling. This study addresses this research gap through a qualitative study based on post-counseling interviews with a sample of 41 elderly persons who received counseling at a dedicated organisation catering to the elderly in Singapore. The qualitative data revealed that clients benefitted from counseling through better emotional management - they received emotional support, found emotional healing and learnt to deal with the emotions associated with grief and loss. Clients also reported that counseling assisted them in decision making processes - older persons were able to conceive of alternatives to their predicament, obtained insights to embark on change, were enabled to take the perspective of others and found validation for their decisions. While many elderly clients greatly appreciated and benefitted from this service, citing demonstrable changes, among the very old such changes were uncommon. Cultural explanations for these differential reports and possible directions for much needed future research are provided. PMID- 27180172 TI - Phytotherapy for Benign Prostatic Hyperplasia. AB - INTRODUCTION: The use of complementary and alternative medications for symptomatic benign prostatic hyperplasia is a lucrative business in the USA with revenues reaching close to US$6.4 billion in sales for the 2014 fiscal year. Yet, despite its popularity, the evidence supporting the continued use of phytotherapy for symptomatic benign prostatic hyperplasia (BPH) is questionable and a topic worth investigation given its wide spread use. METHODS: A comprehensive literature search utilizing Medline and PubMed was conducted to identify literature pertaining to phytotherapy for the management of BPH. Agents with at least modest clinical data were selected for in-depth review including Seronoa repens, Pygeum africanum, Secale cereale, and Hypoxis rooperi. RESULTS: Early clinical trials for each of the agents demonstrated mixed efficacy results with many studies pointing to a possible benefit for phytotherapy. On further examination of these studies, significant confounders such as poor product standardization, study design, and follow-up duration were identified. More recent, larger and more soundly constructed studies found no significant benefit for the use of phytotherapy in the treatment of BPH. CONCLUSIONS: Twenty years ago, the urologic community was encouraged by trial results that suggested phytotherapy could effectively treat symptomatic benign prostatic hyperplasia. Since that time, several well-constructed studies have consistently demonstrated that these agents are no more efficacious than placebo, despite being largely safe for ingestion. PMID- 27180173 TI - Epidermal growth factor receptor inhibitor cancer drug gefitinib modulates cell growth and differentiation of acute myeloid leukemia cells via histamine receptors. AB - BACKGROUND: Epidermal growth factor receptor (EGFR) inhibitor gefitinib (Iressa) is used for treating non-small cell lung cancer. Gefitinib also induces differentiation in acute myeloid leukemia (AML) cell lines and patient samples lacking EGFR by an unknown mechanism. Here we dissected the mechanism of gefitinib action responsible for its EGFR-independent effects. METHODS: Signaling events were analyzed by homogenous time-resolved fluorescence and immunoblotting. Cellular proliferation and differentiation were assessed by ATP measurement, trypan blue exclusion, 5-bromo-2'-deoxyuridine incorporation and flow-cytometry. Gefitinib and G protein-coupled receptor (GPCR) interactions were assessed by beta-arrestin recruitment, luciferase and radioligand competition assays. Role of histamine receptors (HR) in gefitinib actions were assessed by HR knockdown or pharmacological modulation. EGFR and HR interaction was assessed by co immunoprecipitation. RESULTS: Gefitinib reduced cyclic AMP content in both AML and EGFR-expressing cells and induced ERK phosphorylation in AML cells. Dibutyryl cAMP or PD98059 suppressed gefitinib-induced AML cell cytostasis and differentiation. Gefitinib bound to and modulated HRs with subtype selectivity. Pharmacological or genetic modulations of H2 and H4 HRs (H2R and H4R) not only suppressed gefitinib-induced cytostasis and differentiation of AML cells but also blocked EGFR and ERK1/2 inhibition in MDA-MB-231 cells. Moreover, in MDA-MB-231 cells gefitinib enhanced EGFR interaction with H4R that was blocked by H4R agonist 4-methyl histamine (4MH). CONCLUSION: HRs play critical roles in anti cancer effects of gefitinib in both EGFR-deficient and EGFR-rich environments. GENERAL SIGNIFICANCE: We furnish fresh insights into gefitinib functions which may provide new molecular clues to its efficacy and safety issues. PMID- 27180174 TI - Reproducible preparation of spheroids of pancreatic hormone positive cells from human iPS cells: An in vitro study. AB - BACKGROUND: Transplantation of islets of Langerhans is regarded as a promising therapy for type 1 diabetes. A large number of beta-cells are required for the treatment of human type 1 diabetes. Pluripotent stem cells, such as embryonic stem cells and induced pluripotent stem cells, have been considered as new sources for cell replacement therapy. METHODS: Cell aggregates were prepared from human iPS cells using agarose microwell plates and differentiated into pancreatic endocrine cells by changing the culture media with different additives. RESULTS: After 20days of culture, approximately 30% of cells in aggregates were positive for C-peptide. After another 14days in culture, the cells gained an ability to alter C-peptide release in response to changes in the glucose concentration. CONCLUSIONS: Uniform aggregates of human iPSCs were easily prepared on agarose microwell plates and efficiently differentiated into the pancreatic endocrine lineage. Thus, aggregate culture is a suitable method for preparing islet-like aggregates from human iPSCs. GENERAL SIGNIFICANCE: Our results indicate that the microwell plate is suitable for scaling up the preparation of pancreatic endocrine cells from human iPS cells in a robotic system. PMID- 27180175 TI - Prolyl hydroxylation in elastin is not random. AB - BACKGROUND: This study aimed to investigate the prolyl and lysine hydroxylation in elastin from different species and tissues. METHODS: Enzymatic digests of elastin samples from human, cattle, pig and chicken were analyzed using mass spectrometry and bioinformatics tools. RESULTS: It was confirmed at the protein level that elastin does not contain hydroxylated lysine residues regardless of the species. In contrast, prolyl hydroxylation sites were identified in all elastin samples. Moreover, the analysis of the residues adjacent to prolines allowed the determination of the substrate site preferences of prolyl 4 hydroxylase. It was found that elastins from all analyzed species contain hydroxyproline and that at least 20%-24% of all proline residues were partially hydroxylated. Determination of the hydroxylation degrees of specific proline residues revealed that prolyl hydroxylation depends on both the species and the tissue, however, is independent of age. The fact that the highest hydroxylation degrees of proline residues were found for elastin from the intervertebral disc and knowledge of elastin arrangement in this tissue suggest that hydroxylation plays a biomechanical role. Interestingly, a proline-rich domain of tropoelastin (domain 24), which contains several repeats of bioactive motifs, does not show any hydroxyproline residues in the mammals studied. CONCLUSIONS: The results show that prolyl hydroxylation is not a coincidental feature and may contribute to the adaptation of the properties of elastin to meet the functional requirements of different tissues. GENERAL SIGNIFICANCE: The study for the first time shows that prolyl hydroxylation is highly regulated in elastin. PMID- 27180176 TI - Food Aversions and Cravings during Pregnancy on Yasawa Island, Fiji. AB - Women often experience novel food aversions and cravings during pregnancy. These appetite changes have been hypothesized to work alongside cultural strategies as adaptive responses to the challenges posed by pregnancy (e.g., maternal immune suppression). Here, we report a study that assessed whether data from an indigenous population in Fiji are consistent with the predictions of this hypothesis. We found that aversions focus predominantly on foods expected to exacerbate the challenges of pregnancy. Cravings focus on foods that provide calories and micronutrients while posing few threats to mothers and fetuses. We also found that women who experience aversions to specific foods are more likely to crave foods that meet nutritional needs similar to those provided by the aversive foods. These findings are in line with the predictions of the hypothesis. This adds further weight to the argument that appetite changes may function in parallel with cultural mechanisms to solve pregnancy challenges. PMID- 27180177 TI - A novel approach to evaluating the benefit of post-urinary tract infection renal ultrasonography, using decision curve analysis. AB - BACKGROUND: The benefit of post-urinary tract infection (UTI) sonography to detect clinically significant renal abnormalities remains a subject open to debate. Decision curve analysis (DCA) is a novel method for evaluating the clinical usefulness of diagnostic tests. Our objective was to determine, using DCA, the benefit of post-UTI sonography and of post-UTI sonography with biological markers of inflammation to predict the risk of recurrence of febrile UTI in children aged 2 to 24 months without known uropathy. METHODS: We retrospectively analyzed all children aged 2 to 24 months, without known uropathy, who presented with a first episode of febrile UTI between 2009 and 2012 and followed them for 30 months. We then used DCA to estimate the benefit of post UTI sonography or post-UTI sonography + biological markers of inflammation for detecting the risk of recurrence. RESULTS: A total of 318 children [144 boys (45.3 %) and 174 girls (54.7 %)], with a mean age of 6.9 +/- 5.6 months, were identified. Of these, 210 children presented with a significant inflammation [66.2 %; 95 % confidence interval (CI) 61.0-71.4], and 30 (9.4 %; 95 % CI 6.2 12.6) presented with abnormal post-UTI sonographic findings. Eighteen (5.7 %; 95 % CI 3.1-8.2) children presented with recurrent UTI at 30 months. CONCLUSIONS: There were significantly more recurrences in those children who presented with abnormal sonographic findings than in those who did not (relative risk 7.68; 95 % CI 3.03-19.46). However, taking into account the effect of false-positives and false negatives, the DCA revealed that for threshold probabilities of >30 %, at which patients/doctors are concerned about unnecessary interventions (whether tests or treatments), neither post-UTI sonography nor post-UTI sonography + biological markers of inflammation have sufficient value to improve care. PMID- 27180179 TI - Genius and psychopathology of the Italian poet Giacomo Leopardi (1798-1837): Paolo Mantegazza's (1831-1910) criticism of the Lombrosian thought. PMID- 27180178 TI - Efficacy and outcomes of continuous peritoneal dialysis versus daily intermittent hemodialysis in pediatric acute kidney injury. AB - BACKGROUND: Acute kidney injury (AKI) requiring renal replacement therapy (RRT) is associated with high patient morbidity and mortality. There is no consensus on the best RRT modality for pediatric AKI. METHODS: The efficacy and safety of continuous peritoneal dialysis (cPD) and daily intermittent hemodialysis (dHD) were compared in 136 children aged 1 month to 16 years requiring RRT for AKI. Mortality, risk factors and causes of death, 1-month and 3-month renal recovery rates, and technique-related complications were assessed. RESULTS: Uremia control and the rate of catheter-related complications were comparable in the groups. Thirty-day survival was 60.7 % (51 out of 84) with cPD and 36.5 % (19 out of 52) with dHD (p = 0.019). Although age <1 year, extended time lag from disease onset to RRT initiation, mechanical ventilation, and extended vasopressor dependence independently predicted death, adjusted mortality was higher with dHD relative to cPD (hazard ratio [HR] 1.75, 95%CI 1.18-2.84, p = 0.022). Almost all fatalities in the dHD group (94 %) occurred during or within an hour of a HD session. Renal function normalized in 27 % of survivors after 4 weeks and in 51 % after 3 months. The risk of permanent end-stage renal disease was increased in patients with an intrinsic renal cause of AKI (HR 2.72; 95 % CI 1.37-3.83; p = 0.029) and in those with delayed RRT initiation (HR 2.17; 95 % CI 123-2.93; p = 0.015), but did not differ between patients treated with dHD and cPD. CONCLUSIONS: Favorable patient survival with cPD compared with dHD in children treated for AKI was evident in this study. PMID- 27180180 TI - Epigenetics: spotlight on type 2 diabetes and obesity. AB - Type 2 diabetes (T2D) and obesity are the major public health problems. Substantial efforts have been made to define loci and variants contributing to the individual risk of these disorders. However, the overall risk explained by genetic variation is very modest. Epigenetics is one of the fastest growing research areas in biomedicine as changes in the epigenome are involved in many biological processes, impact on the risk for several complex diseases including diabetes and may explain susceptibility. In this review, we focus on the role of DNA methylation in contributing to the risk of T2D and obesity. PMID- 27180181 TI - Delay and probability discounting by drug-dependent cocaine and marijuana users. AB - RATIONALE: Steep discounting of delayed monetary rewards by substance-dependent individuals is well-established. Less is known, however, about discounting other kinds of outcomes, and very little is known about discounting by marijuana dependent individuals. OBJECTIVES: To determine how cocaine-dependent individuals and marijuana-dependent individuals discount various delayed and probabilistic outcomes, both positive and negative. METHODS: Marijuana-dependent individuals, cocaine-dependent individuals, and controls performed delay and probability discounting tasks with various hypothetical outcomes. RESULTS: The cocaine dependent (but not the marijuana-dependent) group discounted delayed liquid rewards and monetary gains, but not delayed losses, more steeply than the control group. In contrast, the marijuana-dependent group (but not the cocaine-dependent group) discounted delayed monetary losses more steeply than controls. There were no group differences in discounting for any of the probabilistic outcomes. Factor analysis revealed a delayed gain factor, a probabilistic gain factor, and a delayed/probabilistic loss factor. The delayed gain factor scores for the cocaine dependent group, but not the marijuana-dependent group, differed significantly from those of the control group. The groups did not differ in their probabilistic gain factor scores, and the marijuana-dependent group did not differ from the controls with respect to their loss factor scores. CONCLUSIONS: These results are inconsistent with the idea that steep discounting of both gains and losses and both delayed and probabilistic outcomes reflects a general impulsivity trait, as well as with the idea that all drug-dependent individuals are steep discounters. Rather, differences in discounting appear to be related to both the type of outcome and the specific drug on which individuals are dependent. PMID- 27180182 TI - Voxel-based comparative analysis of lung lesions in CT for therapeutic purposes. AB - Lung cancer remains as one of the most incident types of cancer throughout the world. Temporal evaluation has become a very useful tool when one wishes to analyze some malignancy-indicating behavior. The objective of the present work is to detect changes in the local densities of lung lesions over time (follow-up analysis). From the detected changes, local information as well as extent region of changes can complement the studies regarding the malignant or benign nature of the lesion. Based on this idea, we attempt to use techniques that allow the observation of changes in the lesion over time, based on remote sensing techniques which highlight changes occurring in the environment. The techniques used were the image differencing, image rationing, median filtering, image regression and the fuzzy XOR operator. Based on the global measurement of change percentage in the density, we found density variations which were considered significant in a range from 2.22 to 36.57 % of the volume of the lesion. The results achieved are promising since, besides the visual aspects of the changes in density of the lung lesion over time, we managed to quantify these changes and compare them by volumetric analysis, a more commonly used technique for analysis of changes in lung lesions. PMID- 27180183 TI - Screening outcome in women repeatedly recalled for the same mammographic abnormality before, during and after the transition from screen-film to full field digital screening mammography. AB - OBJECTIVE: The aim of this study was to retrospectively determine screening outcome in women recalled twice for the same mammographic lesion before, during, and after transition from screen-film (SFM) to full-field digital screening mammography (FFDM). METHODS: We included women with a repeated recall for the same mammographic abnormality (37 at subsequent SFM-screening, obtained between January 2000-April 2010; respectively 54 and 65 women with a prior SFM-screen or FFDM-screen followed by subsequent FFDM-screening, obtained between May 2009-July 2013). RESULTS: At SFM-screening, repeated recalls for the same lesion comprised 1.2 % of recalls (37/3217), including 13 malignancies (positive predictive value (PPV), 35.1 %). During the SFM to FFDM transition (SFM-screen followed by FFDM screen), FFDM recalls comprised more repeated recalls for the same lesion (2.2 %, P = 0.002), with a lower PPV (14.8 %, P = 0.02). This proportion increased to 2.8 % after transition to FFDM (i.e., two successive FFDM-screens), with 16 malignancies (PPV, 24.6 %). Invasive cancers at repeated recall were smaller than interval cancers (T1a-c, 79.4 versus 46.8 %, P = 0.001), with less lymph node involvement (20.6 versus 46.5 %, P = 0.007). CONCLUSIONS: More women are repeatedly recalled for the same mammographic abnormality during and after the transition from SFM to FFDM-screening, with comparable cancer risks before and after the transition. These cancers show better prognostic characteristics than interval cancers. KEY POINTS: * FFDM-screening increases the number of repeated recalls for the same mammographic abnormality. * The PPV of these recalls is comparable before and after transition to FFDM-screening. * Cancers diagnosed after a repeated recall are smaller than interval cancers. * These cancers also show less lymph node involvement than interval cancers. PMID- 27180184 TI - Predictors of treatment response following aspiration sclerotherapy of hepatic cysts: an international pooled analysis of individual patient data. AB - OBJECTIVES: To identify predictive variables of treatment response following aspiration sclerotherapy of large symptomatic hepatic cysts. METHODS: We collected individual patient data from two tertiary referral centres and included all patients treated with aspiration sclerotherapy of a large (>5 cm), symptomatic hepatic cyst. At six months, clinical response was defined as complete or incomplete. Secondary, suboptimal technical response was defined as lower quartile of cyst reduction. Predictive variables of clinical and technical response were analyzed by logistic regression analysis. RESULTS: We included 86 patients (58 +/- 10 years; female 90 %). Complete clinical response rate was 55 %. Median cyst diameter and volume reduction were 71 % (IQR 50-87 %) and 98 % (IRQ 88-100 %), respectively. Patients with complete clinical response had a significantly higher cyst reduction compared to incomplete responders (OR 1.02, 95 % CI 1.00-1.04). Aspiration of haemorrhagic cyst fluid (OR 4.39, 95 % CI 1.34 14.39) or a lower cyst reduction at one month (OR 1.06, 95 % CI 1.02-1.10) was associated with a suboptimal technical response at six months. CONCLUSION: Complete clinical response is associated with effective cyst reduction. Aspiration of haemorrhagic cyst fluid or a restricted diameter reduction at one month predicts a suboptimal technical treatment response, however, these variables did not predict symptom disappearance. KEY POINTS: * Aspiration sclerotherapy of hepatic cysts shows excellent clinical and technical efficacy. * Optimal clinical responders have a markedly higher cyst reduction. * Haemorrhagic aspirate and a strong fluid reaccumulation predict suboptimal cyst reduction. PMID- 27180185 TI - Use of intravoxel incoherent motion diffusion-weighted MR imaging for assessment of treatment response to invasive fungal infection in the lung. AB - OBJECTIVES: The purpose of this study was to determine whether intravoxel incoherent motion (IVIM) -derived parameters and apparent diffusion coefficient (ADC) could act as imaging biomarkers for predicting antifungal treatment response. METHODS: Forty-six consecutive patients (mean age, 33.9 +/- 13.0 y) with newly diagnosed invasive fungal infection (IFI) in the lung according to EORTC/MSG criteria were prospectively enrolled. All patients underwent diffusion weighted magnetic resonance (MR) imaging at 3.0 T using 11 b values (0-1000 sec/mm2). ADC, pseudodiffusion coffiecient D*, perfusion fraction f, and the diffusion coefficient D were compared between patients with favourable (n=32) and unfavourable response (n=14). RESULTS: f values were significantly lower in the unfavourable response group (12.6%+/-4.4%) than in the favourable response group (30.2%+/-8.6%) (Z=4.989, P<0.001). However, the ADC, D, and D* were not significantly different between the two groups (P>0.05). Receiver operating characteristic curve analyses showed f to be a significant predictor for differentiation, with a sensitivity of 93.8% and a specificity of 92.9%. CONCLUSIONS: IVIM-MRI is potentially useful in the prediction of antifungal treatment response to patients with IFI in the lung. Our results indicate that a low perfusion fraction f may be a noninvasive imaging biomarker for unfavourable response. KEY POINTS: * Recognition of IFI indicating clinical outcome is important for treatment decision-making. * IVIM can reflect diffusion and perfusion information of IFI lesions separately. * Perfusion characteristics of IFI lesions could help differentiate treatment response. * An initial low f may predict unfavourable response in IFI. PMID- 27180187 TI - Introducing a new scoring system for pap smear in the detection of high-grade squamous intraepithelial lesions in pregnancy (The Luebeck Score). AB - PURPOSE: To construct a scoring system for pap smears to objectify cytological appraisal and to enhance the accuracy and comparability of pap smear interpretation in pregnancy. MATERIALS AND METHODS: For development of a scoring system for cell appraisal of pap smears the style of the Modified Masood's Scoring Index for appraisal of cells from fine needle aspirations of breast lesions was used. Cohort analysis of n = 54 dysplastic pap smears for polymorphology of cells, anisonucleosis, structure of the nucleus, signs of tissue destruction, nucleus/plasma relation and signs of tumordiathesis. Each criteria was classified into three stages: The first with little evidence for dysplasia (one point), second stage with sporadic evidence (two points) or third stage with frequent evidence (three points). To further evaluate if pregnancy associated cells changes interfere with this scoring system we compared the results of pregnant and non-pregnant women. Histological result was used as an indicator of correctness of the score. RESULTS: Statistical analysis showed a good correlation of the scoring system with histological results. Especially in pregnancy statistical analysis shows promising results (sensitivity 86.67 %, Specificity 100 %, receiver operating characteristic analysis p <= 0.05). CONCLUSION: The Luebeck Score seems to be a useful approach for appraisal of pap smears in pregnancy. Further studies containing high numbers of cases are needed for further evaluation of potential benefits of the scoring system compared to conventional evaluation of pap smears. PMID- 27180186 TI - Thoracic staging with 18F-FDG PET/MR in non-small cell lung cancer - does it change therapeutic decisions in comparison to 18F-FDG PET/CT? AB - OBJECTIVE: To investigate whether differences in thoracic tumour staging between 18F-FDG PET/CT and PET/MR imaging lead to different therapeutic decisions in Non Small Cell Lung Cancer (NSCLC). MATERIAL AND METHODS: Seventy-seven NSCLC patients that underwent whole-body 18F-FDG PET/CT from the base of skull to the upper thighs and thoracic PET/MR were enrolled in this retrospective study. Thoracic PET/CT and PET/MR images were staged according to the 7th edition of the AJCC staging manual. Staging results of both modalities were discussed separately in a simulated interdisciplinary tumour board and therapeutic decisions based on both imaging modalities were recorded. Descriptive statistics were used to compare the results and reasons for changes in the therapeutic decision were investigated. RESULTS: Staging results differed in 35 % of patients (27 patients) between thoracic PET/CT and PET/MR. Differences were detected when assessing the T-stage in 18 % (n = 14), the N-stage in 23 % (n = 18), and the M-stage in 1 % (n = 1). However, patient therapy management was changed in only six patients (8 %). CONCLUSION: Despite the variability of thoracic 18F-FDG PET/CT and PET/MR in TNM staging, both modalities lead to comparable therapeutic decisions in patients suffering from NSCLC. Hence, 18F-FDG PET/MR can be considered an possible alternative to 18F-FDG PET/CT for clinical NSCLC staging. KEY POINTS: * PET/CT and PET/MR provide comparable results in early stages in NSCLC * Clinical impact of different staging results has not been investigated * PET/CT and PET/MR lead to comparable therapeutic decisions * PET/MR can be considered an alternative to PET/CT for NSCLC staging. PMID- 27180188 TI - Erratum to: Proof-of Concept that an Acute Trophic Factors Intervention After Spinal Cord Injury Provides an Adequate Niche for Neuroprotection, Recruitment of Nestin-Expressing Progenitors and Regeneration. PMID- 27180189 TI - Resveratrol Attenuates Abeta25-35 Caused Neurotoxicity by Inducing Autophagy Through the TyrRS-PARP1-SIRT1 Signaling Pathway. AB - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of beta-amyloid peptide (Abeta) and loss of neurons. Resveratrol (RSV) is a natural polyphenol that has been found to be beneficial for AD through attenuation of Abeta-induced toxicity in neurons both in vivo and in vitro. However, the specific underlying mechanisms remain unknown. Recently, autophagy was found to protect neurons from toxicity injuries via degradation of impaired proteins and organelles. Therefore, the aim of this study was to determine the role of autophagy in the anti-neurotoxicity effect of RSV in PC12 cells. We found that RSV pretreatment suppressed beta-amyloid protein fragment 25-35 (Abeta25-35) induced decrease in cell viability. Expression of light chain 3-II, degradation of sequestosome 1, and formation of autophagosomes were also upregulated by RSV. Suppression of autophagy by 3-methyladenine abolished the favorable effects of RSV on Abeta25-35-induced neurotoxicity. Furthermore, RSV promoted the expression of sirtuin 1 (SIRT1), auto-poly-ADP-ribosylation of poly (ADP-ribose) polymerase 1 (PARP1), as well as tyrosyl transfer-RNA (tRNA) synthetase (TyrRS). Nevertheless, RSV-mediated autophagy was markedly abolished with the addition of inhibitors of SIRT1 (EX527), nicotinamide phosphoribosyltransferase (STF-118804), PARP1 (AG-14361), as well as SIRT1 and TyrRS small interfering RNA transfection, indicating that the action of RSV on autophagy induction was dependent on TyrRS, PARP1 and SIRT1. In conclusion, RSV attenuated neurotoxicity caused by Abeta25-35 through inducing autophagy in PC12 cells, and the autophagy was partially mediated via activation of the TyrRS-PARP1-SIRT1 signaling pathway. PMID- 27180191 TI - Relationship Between Chronic Tinnitus and Glial Cell Line-Derived Neurotrophic Factor Gene rs3812047, rs1110149, and rs884344 Polymorphisms in a Turkish Population. AB - Glial cell line-derived neurotrophic factor (GDNF) plays a key role in early development of central auditory pathway and the inner ear. However, the auditory pathway studies of GDNF gene polymorphisms are scarce in the literature, and the studies especially associated with tinnitus are limited. Our study aimed to identify whether GDNF gene polymorphisms play any roles in the pathophysiology of tinnitus by investigating the relationship between tinnitus and GDNF polymorphisms. A total of 52 patients with chronic tinnitus and ages ranging from 18 to 55 were admitted to the Ear-Nose-Throat outpatient clinic of Celal Bayar University Medical Faculty Hospital of Manisa, Turkey and constituted the study group. Another 42 patients of the same age range, without tinnitus symptoms and lacking any systemic disease, were also admitted to the clinic and formed the control group. The tympanometric, audiological, and psychoacoustic assessments of the subjects were performed. Deoxyribonucleic acid samples obtained using venous blood taken for routine inspections were used to investigate GDNF gene polymorphisms (rs884344, rs3812047, and rs1110149) by polymerase chain reaction based restriction fragment length polymorphism method. No correlation could be detected between GDNF rs884344 and rs3812047 polymorphisms and subjects with tinnitus (p > 0.05). Heterozygosity was significantly lower for GDNF rs1110149 polymorphism in tinnitus subjects compared to the controls (p < 0.05). However, the allele frequencies for all 3 polymorphisms were not significantly different between tinnitus and control groups (p > 0.05). Failure to detect correlations between tinnitus and GDNF gene polymorphisms suggests this may be due to the fact that the GDNF gene has a variable expression pattern in different tissues and pathologies. Therefore, the study should be improved and its scope should be expanded by including a larger group of patients and different tissues to investigate the expression pattern of GDNF. PMID- 27180190 TI - Protective Effect of Aliskiren in Experimental Ischemic Stroke: Up-Regulated p PI3K, p-AKT, Bcl-2 Expression, Attenuated Bax Expression. AB - Aliskiren (ALK), a pharmacological renin inhibitor, is an effective antihypertensive drug and has potent anti-apoptotic activity, but it is currently unknown whether ALK is able to attenuate brain damage caused by acute cerebral ischemia independent of its blood pressure-lowering effects. This study aimed to investigate the role of ALK and its potential mechanism in cerebral ischemia. C57/BL6 mice were subjected to transient middle cerebral artery occlusion (tMCAO) and treated for 5 days with Vehicle or ALK (10 or 25 mg/kg per day via intragastric administration), whereas Sham-operated animals served as controls. Treatment with ALK significantly improved neurological deficits, infarct volume, brain water content and Nissl bodies after stroke (P < 0.05), which did not affect systemic blood pressure. Furthermore, the protection of ALK was also related to decreased levels of apoptosis in mice by enhanced activation of phosphatidylinositol 3-kinase (PI3K)/AKT pathway, increased level of Bcl-2 and reduced Bax expression (P < 0.05). In addition, ALK's effects were reversed by PI3K inhibitors LY294002 (P < 0.05). Our data indicated that ALK protected the brain from reperfusion injuries without affecting blood pressure, and this effect may be through PI3K/AKT signaling pathway. PMID- 27180192 TI - Antenatal consultation for parents whose child may require admission to neonatal intensive care: a focus group study for media design. AB - BACKGROUND: For parents whose child may require admission to a neonatal intensive care unit (NICU), the antenatal consultation is often their first point of contact with the child's medical team. Consultation challenges health professionals, as parents may be anxious, overwhelmed, or even exhausted by what is and what might occur. Despite consultation being a common practice, there is a paucity of research on how to support practitioners and parents. The purpose of this study was to gain insights into important relational aspects of antenatal consultation that may be used to spur the development of media to support consultation. METHODS: Focus group, as a data collection method, was employed to gather insights about antenatal consultation from a total of 50 hospital staff and 17 NICU parents from a large urban NICU program in western Canada. Qualitative content analysis was applied to the obtained materials to explicate themes that may serve as necessary understandings for media design. RESULTS: Participating hospital staff and parents expressed their desire for a good antenatal consultation with comments grouped under the following themes: supporting the building of a caring relation; sharing information in conversation; and, preparing for what is to come. CONCLUSIONS: To support the emerging relations of baby, parent, and hospital staff, a good antenatal consultation needs to convey care, understanding, and empathy; create possibilities for open and genuine conversations; and, foster the buildings of respect, confidence, and trust. PMID- 27180193 TI - Quantifying the plant actin cytoskeleton response to applied pressure using nanoindentation. AB - Detection of potentially pathogenic microbes through recognition by plants and animals of both physical and chemical signals associated with the pathogens is vital for host well-being. Signal perception leads to the induction of a variety of responses that augment pre-existing, constitutive defences. The plant cell wall is a highly effective preformed barrier which becomes locally reinforced at the infection site through delivery of new wall material by the actin cytoskeleton. Although mechanical stimulation can produce a reaction, there is little understanding of the nature of physical factors capable of triggering plant defence. Neither the magnitude of forces nor the contact time required has been quantified. In the study reported here, mechanical stimulation with a tungsten microneedle has been used to quantify the response of Arabidopsis plants expressing an actin-binding protein tagged with green fluorescent protein (GFP) to reveal the organisation of the actin cytoskeleton. Using confocal microscopy, the response time for actin reorganisation in epidermal cells of Arabidopsis hypocotyls was shown to be 116 +/- 49 s. Using nanoindentation and a diamond spherical tip indenter, the magnitude of the forces capable of triggering an actin response has been quantified. We show that Arabidopsis hypocotyl cells can detect a force as small as 4 MUN applied for as short a time as 21.6 s to trigger reorganisation of the actin cytoskeleton. This force is an order of magnitude less than the potential invasive force determined for a range of fungal and oomycete plant pathogens. To our knowledge, this is the first quantification of the magnitude and duration of mechanical forces capable of stimulating a structural defence response in a plant cell. PMID- 27180194 TI - Different functions of the histone acetyltransferase HAC1 gene traced in the model species Medicago truncatula, Lotus japonicus and Arabidopsis thaliana. AB - In eukaryotes, histone acetyltransferases regulate the acetylation of histones and transcription factors, affecting chromatin structural organization, transcriptional regulation, and gene activation. To assess the role of HAC1, a gene encoding for a histone acetyltransferase in Medicago truncatula, stable transgenic lines with modified HAC1 expression in the model plants M. truncatula, Lotus japonicus, and Arabidopsis thaliana were generated by Agrobacterium mediated transformation and used for functional analyses. Histochemical, transcriptional, flow cytometric, and morphological analyses demonstrated the involvement of HAC1 in plant growth and development, responses to internal stimuli, and cell cycle progression. Expression patterns of a reporter gene encoding beta-glucuronidase (GUS) fused to the HAC1 promoter sequence were associated with young tissues comprised of actively dividing cells in different plant organs. The green fluorescent protein (GFP) signal, driven by the HAC1 promoter, was detected in the nuclei and cytoplasm of root cells. Transgenic lines with HAC1 overexpression and knockdown showed a wide range of phenotypic deviations and developmental abnormalities, which provided lines of evidence for the role of HAC1 in plant development. Synchronization of A. thaliana root tips in a line with HAC1 knockdown showed the involvement of this gene in the acetylation of two core histones during S phase of the plant cell cycle. PMID- 27180195 TI - Meiosis, Balbiani body and early asymmetry of Thermobia oocyte. AB - The meiotic division guarantees maintenance of a genetic diversity; it consists of several stages, with prophase I being the longest and the most complex. We decided to follow the course of initial stages of meiotic division in ovaries of Thermobia domestica using modified techniques of squash preparations, semithin sections, and electron microscopy. We show that germaria contain numerous germline cells that can be classified into three categories: cystoblasts, meiotic oocytes, and growing previtellogenic oocytes. The cystoblasts are located most apically. The meiotic oocytes occupy the middle part of the germarium, and the previtellogenic oocytes can be found in the most basal part, near the vitellarium. Analyses of the semithin sections and squash preparations show that post leptotene meiotic chromosomes gather in one region of the nucleoplasm where they form the so-called bouquet. The telomeres of the bouquet chromosomes are attached to a relatively small area (segment) of the nuclear envelope. Next to this envelope segment, the nucleolar organizers are also located. We show that in concert to sequential changes inside the oocyte nuclei, rearrangement of organelles within the ooplasm (oocyte cytoplasm) takes place. This leads to the formation of the Balbiani body and consequent asymmetry of the ooplasm. These early nuclear and cytoplasmic asymmetries, however, are transient. During diplotene, the chromosome bouquet disappears, while the Balbiani body gradually disperses throughout the ooplasm. Finally, our observations indicate the presence of lampbrush chromosomes in the nuclei of previtellogenic oocytes. In the close vicinity to lampbrush chromosomes, characteristic spherical nuclear bodies are present. PMID- 27180196 TI - A first vascularized skin equivalent as an alternative to animal experimentation. AB - Tissue-engineered skin equivalents mimic key aspects of the human skin, and can thus be employed as wound coverage for large skin defects or as in vitro test systems as an alternative to animal models. However, current skin equivalents lack a functional vasculature limiting clinical and research applications. This study demonstrates the generation of a vascularized skin equivalent with a perfused vascular network by combining a biological vascularized scaffold (BioVaSc) based on a decellularized segment of a porcine jejunum and a tailored bioreactor system. Briefly, the BioVaSc was seeded with human fibroblasts, keratinocytes, and human microvascular endothelial cells. After 14 days at the air-liquid interface, hematoxylin & eosin and immunohistological staining revealed a specific histological architecture representative of the human dermis and epidermis including a papillary-like architecture at the dermal-epidermal junction. The formation of the skin barrier was measured non-destructively using impedance spectroscopy. Additionally, endothelial cells lined the walls of the formed vessels that could be perfused with a physiological volume flow. Due to the presence of a complex in-vivo-like vasculature, the here shown skin equivalent has the potential for skin grafting and represents a sophisticated in vitro model for dermatological research. PMID- 27180197 TI - Association between IFNL4 rs368234815 polymorphism and sustained virological response in chronic hepatitis C patients undergoing PEGylated interferon/ribavirin therapy: A meta-analysis. AB - BACKGROUND AND AIMS: Many studies have been published on the association between IFNL4 rs368234815 single-nucleotide polymorphism (SNP) and sustained virological response (SVR) in chronic hepatitis C (CHC) patients undergoing treatment with PEGylated interferon (PEG-IFN) plus ribavirin (RBV). Because of the variable and sometimes inconsistent results, we performed a meta-analysis to estimate the association between these factors. METHODS: We conducted a search of the literature published prior to July 1, 2014. The pooled results were analyzed as the odds ratios (ORs) and corresponding 95% confidence intervals (CIs) using random-effect model. RESULTS: The pooled results revealed that the rs368234815 TT/TT genotype was significantly correlated with SVR in HCV-1/4-infected Caucasian patients (OR=4.65, 95% CI=3.36-6.42, P<0.00001) but not in HCV-2/3 infected Caucasian patients (OR=1.44, 95% CI: 0.89-2.33, P=0.13). Conversely, the rs368234815 DeltaG/DeltaG genotype was significantly linked to treatment failure in Caucasian patients (OR=0.49, 95% CI: 0.38-0.64, P<0.00001), regardless of the HCV genotype. CONCLUSION: The results of the meta-analysis suggest that IFNL4 rs368234815 polymorphism may be a predictor of SVR in Caucasian HCV-1/4-infected patients. PMID- 27180198 TI - Mannose-binding lectin gene (MBL2) polymorphisms related to the mannose-binding lectin low levels are associated to dengue disease severity. AB - Dengue is the main arbovirosis in the tropical and subtropical areas of the world. The majority of infected individuals present an asymptomatic outcome while others progress to dengue fever (DF) or dengue haemorrhagic fever (DHF). Dengue infection evolution to severe outcomes is in part, related to innate immunity response. The MBL2 gene encodes for a pathogen recognition pattern molecule, the mannose-binding lectin (MBL). Variant alleles at promoter and structural regions of the MBL2 are related to serum MBL levels and function. Due to the important inflammatory modulation role of MBL, MBL2 polymorphisms could influence dengue progression. Therefore, this study investigated associations of MBL2 polymorphisms and serum MBL levels in patients with dengue. Genotyping of promoter and structural regions of MBL2 was performed by real-time PCR using Taqman(r) probes in 161 patients presenting DF or DHF outcome. For the serum MBL determination a commercial ELISA kit was used. The variant OO genotype and O allele were associated with DHF (p=0.008 and p=0.009 respectively). Haplotypes correlated to MBL low levels were associated with DHF (p=0.04). Our results support the hypothesis that patients carrying genotypes or haplotypes of low production of MBL would be more susceptible to DHF. PMID- 27180199 TI - Reply to "Improved postoperative mortality rates after thoracic surgery for lung cancer" [CLM-D-16-00187]. PMID- 27180200 TI - Amendment of the cytokine profile in macrophages subsequent to their interaction with smooth muscle cells: Differential modulation by fractalkine and resistin. AB - In atherosclerotic plaques, macrophages (MAC) and smooth muscle cells (SMC) frequently reside in close proximity and resistin (Rs) and fractalkine (Fk) are present at increased levels, resistin being associated with CD68 macrophages and fractalkine predominantly associated with intimal SMC; however, their role in this location is not clear, yet. The objective of this study was to determine whether the cross-talk between MAC-SMC induces changes in MAC cytokine phenotype and if Fk and Rs have a role in the process. To this purpose, macrophages (THP-1 monocytes differentiated with phorbol myristate acetate) were interacted with SMC cultured on the membrane inserts in the presence or absence of Rs or Fk. After 24h, MAC were removed from the co-culture and the gene and protein expression of 57 cytokines was assessed by QPCR and Proteome ProfilerTM Array. Fk secreted in the culture medium following MAC-SMC interaction was determined (ELISA assay) and the role of Fk in MAC cytokine gene expression was assessed by silencing the Fk receptor in both cell types. The results showed that subsequent to the interaction with SMC, MAC exhibit: (1) a general increased expression of chemokines (the highest fold increase: VCC-1 and GRO-alpha) and of some interleukins, such as interleukins IL-5 (~8-fold) and IL-6; (2) an increased Fk expression that in turn induces expression of: CXCL17, CCL19, CCL2, CXCL10, CXCL12, CXCL4, CXCL7, CCL4, CCL18, CXCL16, CXCL1 and IL-27; (3) in the presence of Rs, a predominant increased expression of interleukins (the highest fold increase: IL-6, IL-27, IL-23 and IL-5) and an augmented expression of some chemokines such as MIP-1beta, GRO-alpha and CCL1. In addition, the secretome collected from the SMC-MAC co-culture increased human monocytes chemotaxis. DAVID analysis of the data revealed that the switch of MAC to a pro-inflammatory phenotype, prime the cells to intervene in the immune response, chemotaxis and inflammatory response. In conclusion, MAC cytokines expression is considerable augmented upon their interaction with SMC and Fk and Rs have distinct immunomodulatory roles: Fk predominantly increases the pro-angiogenic and inflammatory chemokines expression and Rs mostly the pro-inflammatory interleukins with consequences on monocyte chemotaxis. The novel data could help to develop targeted nanotherapies to reduce leukocyte chemotaxis and the ensuing inflammatory process associated with atherosclerosis. PMID- 27180201 TI - Calcitriol decreases pro-inflammatory cytokines and protects against severe hemorrhagic shock induced-organ damage in rats. AB - INTRODUCTION: Resuscitation after hemorrhagic shock (HS) could result in increased pro-inflammatory cytokines and then multiple organ dysfunctions. Calcitriol exerts pleiotropic effects in a wide variety of target tissues and has a role against anti-inflammation. The present study was aimed to investigate the modulatory effects of calcitriol on the pathophysiological and inflammatory markers following HS in rats. MATERIALS AND METHODS: By withdrawing 60% of the total blood volume over 30min via a femoral artery catheter in rats, HS was induced. Afterwards, 10ng/kg calcitriol was injected intravenously in rats. After performing these procedures, hemodynamic status of mean arterial pressure (MAP) and heart rate (HR) were continuously monitored for 12h. Hemoglobin, lactic dehydrogenase (LDH), creatine phosphokinase (CPK), liver and renal function were measured at 30min before the induction of HS and 0, 1, 3, 6, 9, and 12h after HS, while an equal volume of normal saline as replacement fluid. At 1 and 12h after inducing HS, serum levels of tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) levels were measured, and the livers, kidneys and lungs were taken out and then examined histo-pathologically at 48h after inducing HS. RESULTS: Hemoglobin and MAP were significantly decreased, liver and renal function were significantly impaired, but HR and the levels of LDH, CPK, TNF alpha and IL-6 were significantly increased after HS in rats. After being treated with calcitriol following HS resulted in better survival rate, lower serum levels of TNF-alpha and IL-6, and lesser hepatic, renal, and pulmonary histo-pathologic scores of injury in rats. CONCLUSION: Being treated with calcitriol after HS could ameliorate the pro-inflammatory reactions by modulating the effects of cytokines, which lead to prevention of subsequent major organ damages. PMID- 27180202 TI - High serum CXCL10 in Rickettsia conorii infection is endothelial cell mediated subsequent to whole blood activation. AB - BACKGROUND: The pathophysiological hallmark of Rickettsia conorii (R. conorii) infection comprises infection of endothelial cells with perivascular infiltration of T-cells and macrophages. Although interferon (IFN)-gamma-induced protein 10 (IP-10)/CXCL10 is induced during vascular inflammation, data on CXCL10 in R. conorii infection is scarce. METHODS: Serum CXCL10 was analyzed in two cohorts of southern European patients with R. conorii infection using multiplex cytokine assays. The mechanism of R. conorii-induced CXCL10 release was examined ex vivo using human whole blood interacting with endothelial cells. RESULTS: (i) At admission, R. conorii infected patients had excessively increased CXCL10 levels, similar in the Italian (n=32, ~56-fold increase vs controls) and the Spanish cohort (n=38, ~68-fold increase vs controls), followed by a marked decrease after recovery. The massive CXCL10 increase was selective since it was not accompanied with similar changes in other cytokines. (ii) Heat-inactivated R. conorii induced a marked CXCL10 increase when whole blood and endothelial cells were co-cultured. Even plasma obtained from R. conorii-exposed whole blood induced a marked CXCL10 release from endothelial cells, comparable to the levels found in serum of R. conorii-infected patients. Bacteria alone did not induce CXCL10 production in endothelial cells, macrophages or smooth muscle cells. CONCLUSIONS: We show a massive and selective serum CXCL10 response in R. conorii-infected patients, likely reflecting release from infected endothelial cells characterized by infiltrating T cells and monocytes. The CXCL10 response could contribute to T cell infiltration within the infected organ, but the pathologic consequences of CXCL10 in clinical R. conorii infection remain to be defined. PMID- 27180203 TI - Bacoside A and bromelain relieve dichlorvos induced changes in oxidative responses in mice serum. AB - Reactive oxygen species (ROS) may be involved in the pathogenesis of serum induced by dichlorvos. Therefore, the rationale of present research was to evaluate the ameliorative efficacy of bacoside A and bromelain on oxidative stress biomarkers in serum of dichlorvos intoxicated mice. Also the level of serum antioxidants viz. catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and reduced glutathione (GSH) were measured. For experiments, mice were allocated into six groups. First group received saline as a vehicle; second group was administered with dichlorvos (40 mg/kg b.w.); third group was administered with bromelain (70 mg/kg b.w.), fourth group received dose of bacoside A (5 mg/kg b.w.), fifth group was given concomitant exposure of bacoside A and bromelain both and mice of sixth group were exposed to bacoside A, bromelain and dichlorvos for 21 days consecutively. Oxidative stress biomarkers thiobarbituric acid reactive substances (TBARS) and protein carbonyl content (PCC) and antioxidants (CAT, SOD, GPx and GSH) level of serum was determined to elucidate the protective potential of bacoside A and bromelain against dichlorvos intoxication. Significantly increased TBARS and PCC level in second group suggests that dichlorvos enhances the production of free radicals in serum of mice (p < 0.05). Antioxidants treatment significantly decreased the levels of TBARS and PCC (p < 0.05). Dichlorvos administration causes a significant reduction in the level of CAT, SOD, GPx and GSH (p < 0.05) which was restored significantly by co-administration of bromelain and bacoside A in dichlorvos exposed mice (p < 0.05). The bacoside A and bromelain are attributed with antioxidant properties. Finding of research conclude that concomitant exposure of bacoside A and bromelain was much effective in combating oxidative stress induced by dichlorvos. PMID- 27180204 TI - Paris Saponin II induced apoptosis via activation of autophagy in human lung cancer cells. AB - Paris Saponin II (PSII) has been shown anticancer activity against several cancer lines through the pro-apoptotic pathway. The aim of the study was to investigate the relationship between apoptosis and autophagy taking part in the anti-cancer mechanisms of PSII. In this study, PSII induced autophagy and apoptosis in dose- and time-dependent manners. Meanwhile, it induced autophagy as early as 2 h after exposure to 1 MUM of PSII accompanying with apoptosis. Blockade of autophagy with chloroquine (CQ) attenuated apoptosis, while regulation of reactive oxygen species (ROS) by N-acetyl cysteine (NAC), gallic acid (GA) and H2O2 could not influence autophagy. In addition, PSII induced apoptosis via activation of autophagy, which might be associated with the activation of JNK and inhibition of PI3K/AKT/mTOR pathway. All in all, our research increased the understanding of the role of PSII regulating autophagy and apoptosis, which would hopefully provide prospective strategies for cancer therapy. PMID- 27180205 TI - Bovine serum albumin interacts with silver nanoparticles with a "side-on" or "end on" conformation. AB - As the nanoparticles (NPs) enter into the biological interface, they have to encounter immediate and first exposure to many proteins of different concentrations. The physicochemical interaction of NPs and proteins is greatly influenced not only by the number and type of proteins; but also the surface chemistry of NPs. To analyze the effects of NPs on proteins, the interaction between bovine serum albumin (BSA) and silver nanoparticles (AgNPs) at different concentrations were investigated. The interaction, BSA conformations, kinetics and adsorption were analyzed by UV-Visible spectrophotometer, dynamic light scattering (DLS), FT-IR spectroscopy and fluorescence quenching. DLS, FTIR and UV visible spectrophotometric analysis confirms the interaction with minor alterations in size of the protein. Fluorescence quenching analysis confirms the side-on or end-on interaction of 1.5 molecules of BSA to AgNP. Further, pseudo second order kinetics was determined with equilibrium contact-time of 30 min. The data of the present study determines the detailed evaluation of BSA adsorption on AgNP along with mechanism, kinetics and isotherm of the adsorption. PMID- 27180206 TI - Ciprofloxacin toxicity and its co-metabolic removal by a freshwater microalga Chlamydomonas mexicana. AB - This study evaluated the toxicity and cellular stresses of ciprofloxacin (CIP) and its co-metabolic removal in a freshwater microalga Chlamydomonas mexicana. The toxicological effects of CIP on C. mexicana were assessed by studying the growth and biochemical characteristics of the microalga including total chlorophyll, carotenoid content, malondialdehyde (MDA) and superoxide dismutase (SOD) activity. The calculated effective concentration (EC50) of CIP on C. mexicana was 65+/-4mgL-1 at 96h. The growth of C. mexicana was significantly inhibited at increased concentrations of CIP, showing 36+/-1, 75+/-3. and 88+/-3% inhibition at 40, 60 and 100mgL-1 CIP, respectively, compared to the control after 11days of cultivation. The total chlorophyll, carotenoid, MDA and SOD activity were significantly increased as a result of relatively high concentrations of CIP stress. C. mexicana showed 13+/-1% removal of CIP (2mgL-1) after 11days of cultivation; however, the addition of an electron donor (sodium acetate, 4gL-1) highly enhanced the removal of CIP (2mgL-1) by>3-fold after 11days. Kinetic studies showed that removal of CIP followed a first-order model (R2 0.94-0.97) with the apparent rate constants (k) ranging from 0.0121 to 0.079 d-1. PMID- 27180207 TI - Adsorption of diclofenac onto organoclays: Effects of surfactant and environmental (pH and temperature) conditions. AB - Among pharmaceutical products (PPs) recalcitrant to water treatments, diclofenac shows a high toxicity and remains at high concentration in natural aquatic environments. The aim of this study concerns the understanding of the adsorption mechanism of this anionic PP onto two organoclays prepared with two long-alkyl chains cationic surfactants showing different chemical nature for various experimental pH and temperature conditions. The experimental data obtained by a set of complementary techniques (X-ray diffraction, elemental analyses, gas chromatography coupled with mass spectrometry, and Fourier transform infrared spectroscopy) and the use of Langmuir, Freundlich and Dubinin-Radushkevish equation models, reveal that organoclays show a good affinity to diclofenac which is enhanced as the temperature is under 35 degrees C and for pH above 4.5 (i.e. >pKa of diclofenac) while the chemical nature of surfactant appears to play a minor role. The thermodynamic parameters derived from the fitting procedure point out the strong electrostatic interaction with organic cations adsorbed within the interlayer space in the organoclays for the adsorption of diclofenac. This study stress out the application of organoclays for the adsorption of a recalcitrant PPs in numerous aquatic compartments that can be used as a complement with activated carbon for waste water treatment. PMID- 27180208 TI - Degradation of venlafaxine using TiO2/UV process: Kinetic studies, RSM optimization, identification of transformation products and toxicity evaluation. AB - The photochemical degradation of the antidepressant drug venlafaxine (VNF) by UV/TiO2 process was investigated in the present study. Prescreening experiments were conducted to study the effects of main parameters affecting the photocatalytic process. In addition, the effects and interactions of most influenced parameters were evaluated and optimized by using a central composite design model and a response surface methodology. Results indicated that VNF was quickly removed in all the irradiation experiments and its degradation was mainly affected by the studied variables (catalyst dose, initial VNF concentration and pH), as well as their interaction effects. Parallel to kinetic studies, the transformation products (TPs) generated during the treatment was investigated using LC coupled to low and high resolution mass spectrometry. Based on identification of the main TPs, tentative transformation pathways were proposed, including hydroxylation, demethylation and dehydration as major transformation routes. Tauhe potential risk of VNF and its TPs to aqueous organisms was also investigated using Microtox bioassay before and during the processes. The obtained results showed an increment in the acute toxicity in the first stages and a continuously decreasing after then to very low values reached within 240min of the photocatalytic treatment, demonstrating that UV/TiO2 can lead to the elimination of parent compound and the detoxification of the solution. PMID- 27180209 TI - Electrochemical degradation of the antihypertensive losartan in aqueous medium by electro-oxidation with boron-doped diamond electrode. AB - In this work the electrochemical oxidation of losartan, an emerging pharmaceutical pollutant, was studied. Electrochemical oxidation was carried out in batch mode, in an open and undivided cell of 100cm(3) using a boron-doped diamond (BDD)/stainless steel system. With Cl(-) medium 56% of mineralization was registered, while with the trials containing SO4(2-) as supporting electrolyte a higher mineralization yield of 67% was reached, even obtaining a total removal of losartan potassium at 80mAcm(-2) and 180min of reaction time at pH 7.0. Higher losartan potassium concentrations enhanced the mineralization degree and the efficiency of the electrochemical oxidation process. During the mineralization up to 4 aromatic intermediates were identified by ultra high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). Moreover, short-linear carboxylic acids, like oxalic, succinic and oxamic were detected and quantified by ion-exclusion HPLC. Finally, the ability of the electrochemical oxidation process to mineralize dissolved commercial tablets containing losartan was achieved, obtaining TOC removal up to 71% under optimized conditions (10mAcm(-2), 0.05M Na2SO4, pH 7.0 and 25 degrees C and 360min of electrolysis). PMID- 27180210 TI - Brain mechanisms of semantic interference in spoken word production: An anodal transcranial Direct Current Stimulation (atDCS) study. AB - When naming pictures, categorically-related compared to unrelated contexts typically slow production. We investigated proposed roles for the left inferior frontal gyrus (LIFG) and posterior middle and superior temporal gyri (pMTG/STG) in mediating this semantic interference effect. In a three-way, cross-over, sham controlled study, we applied online anodal transcranial Direct Current Stimulation (atDCS) to LIFG or pMTG/STG while 24 participants performed parallel versions of the blocked cyclic naming paradigm. Significant effects of semantic context and cycle, and interactions of context and cycle, were observed on naming latencies in all three stimulation sessions. Additionally, atDCS over left pMTG/STG facilitated naming in related blocks from the second cycle onward, significantly reducing but not eliminating the interference effect. Applying atDCS over left LIFG likewise reduced the magnitude of interference compared to sham stimulation, although the facilitation was limited to the first few cycles of naming. We interpret these results as indicating semantic interference in picture naming reflects contributions of two complementary mechanisms: a relatively short-lived, top-down mechanism to bias selection and a more persistent lexical-level activation mechanism. PMID- 27180211 TI - Optimal calibration of instrumented treadmills using an instrumented pole. AB - Calibration of instrumented treadmills is imperative for accurate measurement of ground reaction forces and center of pressure (COP). A protocol using an instrumented pole has been shown to considerably increase force and COP accuracy. This study examined how this protocol can be further optimized to maximize accuracy, by varying the measurement time and number of spots, using nonlinear approaches to calculate the calibration matrix and by correcting for potential inhomogeneity in the distribution of COP errors across the treadmill's surface. The accuracy increased with addition of spots and correction for the inhomogeneous distribution across the belt surface, decreased with reduction of measurement time, and did not improve by including nonlinear terms. Most of these methods improved the overall accuracy only to a limited extent, suggesting that the maximal accuracy is approached given the treadmill's inherent mechanical limitations. However, both correction for position dependence of the accuracy as well as its optimization within the walking area are found to be valuable additions to the standard calibration process. PMID- 27180212 TI - Characteristics of paraphilics in Turkey: A retrospective study-20years. AB - OBJECTIVE: This study is carried out to research the frequency of occurrence and the characteristics of paraphilic cases in Turkey and forensic aspects of them and to explain forensic psychiatric studies of people show paraphilic actions and assess them from legal aspects. METHOD: This research is done by studying a total of 101,208 cases who were sent to Istanbul Forensic Medicine Institute (FMI) by the judicial organs of 4th Specialization Board between 1984 and 2004 to decide whether they show paraphilic actions or not. When choosing the cases of pedophilic actions, incest incidents were excluded and 307 incidents were taken into assessment. RESULTS: The male subjects are 97.4%, 39.7% of them are 19 29years old, 10% of them are over age 60, 59% of the subjects are single, 36.5% of them are unemployed, 71.7% of the incidents have no physical disorder. The subjects who were imprisoned before were 20.2% and 22.1% of them had undergone psychiatric treatment before the incident. Twenty separate diagnosis are determined by the FMI for the subjects. There were mental retardation, schizophrenia and various personality disorders on the top the diagnosis list. The paraphilia type of the incidents are pedophilia (60.3%), exhibitionism (8.1%), pedophilia and exhibitionism (7.5%) and fetishism (5.9%). It was determined that there were more than one paraphilia type in 40 incidents (13%). FMI decided that 54.7% of them have criminal responsibility, 25.1% of them have no criminal responsibility, and 20.2% of them have reduced criminal responsibility. CONCLUSION: There were 20 separate type of diagnosis for the incidents. It is understood that paraphilic incidents do not seek for help although they have the symptoms of disorder and they are exposed to psychiatric assessment only when they face a criminal inquiry. This suggests that there are more paraphilic incidents in the society than what we encounter. PMID- 27180213 TI - Violence and mental disorders. A retrospective study of people in charge of a community mental health center. AB - BACKGROUND: Numerous studies conducted in inpatient settings have highlighted how mental disorders are associated with an increased risk of violence, particularly during acute phases. However, to date a more limited number of studies have been performed to assess the risk of violence in outpatients, particularly in Italy. The present study aims to evaluate the prevalence of violent events in a sample of patients in charge of a community mental health center in Italy. METHODS: Based on data obtained from standardized clinical records, a retrospective study was undertaken to investigate acts of violence (physical aggression only) in a total of 678 patients (Males=308, 45.4%) in charge of a university mental health center; patients were mainly affected by anxiety disorders (30.7%), depressive disorder (17.2%), bipolar disorder (18.3%) and schizophrenia or other psychotic disorders (25.0%). RESULTS: 27.6% of the sample had committed at least one act of violence during their lifetime, 10.5% over the previous year. 56.7% of those who committed violence acts had acted violently twice or more during their lifetime. A significant association of lifetime violence was found with gender (male), younger age, low education, unemployment, living with parents. With regard to diagnosis, a significant association was found with schizophrenia and other psychotic disorders, personality disorders, mental retardation, and comorbidity between two or more psychiatric disorders. Violence was moreover associated with early age at onset and at first psychiatric treatment, longer duration of the disorder, previous hospital admissions, previous violent events. CONCLUSION: Violent behavior is relatively common among outpatients. PMID- 27180214 TI - Drug-eluting Balloon Versus Second Generation Drug Eluting Stents in the Treatment of In-stent Restenosis: A Systematic Review and Meta-analysis. AB - BACKGROUND: In-stent restenosis (ISR) remains a significant mode of stent failure following PCI. The optimal treatment strategy, however, remains undefined and the role of drug-eluting balloons (DEB) in the management of ISR is also unclear. METHODS: A meta-analysis was performed to compare the efficacy of DEB in the treatment of ISR against second generation drug eluting stents (DES). RESULTS: Seven studies comprised of 1,065 patients were included for analysis. The follow up period ranged from 12-25 months. The use of DEB was associated with an inferior acute gain in minimal luminal diameter (MLD) (0.36, 95% CI: 0.16 0.57mm), higher late loss in MLD (0.11, 0.02-0.19mm) and a higher binary restenosis rate at follow-up (risk ratio: 2.24, 1.49-3.37). No significant differences were noted in the overall incidence of the analysed clinical parameters between the two groups. When only the randomised controlled trials (RCT) were considered however, there was a strong trend towards higher target lesion revascularisation (TLR; 9.9% vs. 3.6%; RR: 2.5, p=0.07) and a significantly higher major adverse cardiovascular event (MACE) rate (15.7% vs. 8.8%; RR 1.78; p=0.02) with DEB. CONCLUSION: While equipoise has been demonstrated in selected clinical outcomes between DEB and second generation DES in the treatment of ISR, the suboptimal angiographic outcome at follow-up and the higher TLR and MACE rates associated with DEB observed in the RCT are concerning. The results of the present analysis should be regarded as preliminary, although the generalised adoption of DEB in the treatment of ISR currently cannot be recommended. PMID- 27180215 TI - Non-Invasive Cardiac Imaging: Past, Present and Future. PMID- 27180216 TI - DNA barcoding of Sri Lankan phlebotomine sand flies using cytochrome c oxidase subunit I reveals the presence of cryptic species. AB - Sri Lanka is known for high diversity of phlebotomine sand flies and prevalence of cutaneous and visceral leishmaniasis; a disease vectored by sand flies. The taxonomy of phlebotomine sand flies is complicated and often the diversity is over/underrated. The current study aims to use the cytochrome c oxidase gene subunit 1 (COI) sequence and formulate a barcode for the sand fly species in Sri Lanka. A total of 70 samples comprising seven species morphologically identified and collected from dry zone districts of Hambantota, Anuradhapura, Vavuniya, Trincomalee and Jaffna were processed. Neighbour-joining (NJ) tree created using the sequences revealed the species identity is compatible with the current morphology based identification. Further the analysis delineated morphologically identified Se. bailyi, Se babu babu and Se babu insularis into genetically distinct groups. PMID- 27180218 TI - Plant lipid biology. PMID- 27180217 TI - Mu suppression - A good measure of the human mirror neuron system? AB - Mu suppression has been proposed as a signature of the activity of the human mirror neuron system (MNS). However the mu frequency band (8-13 Hz) overlaps with the alpha frequency band, which is sensitive to attentional fluctuation, and thus mu suppression could potentially be confounded by changes in attentional engagement. The specific baseline against which mu suppression is assessed may be crucial, yet there is little consistency in how this is defined. We examined mu suppression in 61 typical adults, the largest mu suppression study so far conducted. We compared different methods of baselining, and examined activity at central and occipital electrodes, to both biological (hands) and non-biological (kaleidoscope) moving stimuli, to investigate the involvement of attention and alpha activity in mu suppression. We also examined changes in beta power, another candidate index of MNS engagement. We observed strong mu suppression restricted to central electrodes when participants performed hand movements, demonstrating that mu is indeed responsive to the activity of the motor cortex. However, when we looked for a similar signature of mu suppression to passively observed stimuli, the baselining method proved to be crucial. Selective suppression for biological versus non-biological stimuli was seen at central electrodes only when we used a within-trial baseline based on a static stimulus: this method greatly reduced trial-by-trial variation in the suppression measure compared with baselines based on blank trials presented in separate blocks. Even in this optimal condition, 16-21% of participants showed no mu suppression. Changes in beta power also did not match our predicted pattern for MNS engagement, and did not seem to offer a better measure than mu. Our conclusions are in contrast to those of a recent meta-analysis, which concluded that mu suppression is a valid means to examine mirror neuron activity. We argue that mu suppression can be used to index the human MNS, but the effect is weak and unreliable and easily confounded with alpha suppression. PMID- 27180219 TI - Experimental investigation on feasible bioreactor using mechanism of hydrogen oxidation of natural soil for detritiation system. AB - A passive reactor for tritium oxidation at room temperature has been widely studied in nuclear engineering especially for a detritiation system (DS) of a tritium process facility taking possible extraordinary situation severely into consideration. We have focused on bacterial oxidation of tritium by hydrogen oxidizing bacteria in natural soil to realize the passive oxidation reactor. The purpose of this study was to examine the feasibility of a bioreactor with hydrogen-oxidizing bacteria in soil from a point of view of engineering. The efficiency of the bioreactor was evaluated by kinetics. The bioreactor packed with natural soil shows a relative high conversion rate of tritium under the saturated moisture condition at room temperature, which is obviously superior to that of a Pt/Al2O3 catalyst generally used for tritium oxidation in the existing tritium handling facilities. The order of reaction for tritium oxidation with soil was the pseudo-first order as assessed with Michaelis-Menten kinetics model. Our engineering suggestion to increase the reaction rate is the intentional addition of hydrogen at a small concentration in the feed gas on condition that the oxidation of tritium with soil is expressed by the Michaelis-Menten kinetics model. PMID- 27180220 TI - Gamma radiation transmission along the multibend mazes. AB - Installing a maze on the corridor reduces much shielding materials in shielding door at the end of the pathway. In this study, gamma transmission was measured along single-, double-, and triple-bend mazes, which were applied to nondestructive test workplace by Monte Carlo method. In the facility using (192)Ir 1.85TBq, the lengths of corridors to reduce the effective dose under the limitation without shielding door were 10 and 6m in double- and triple-bend mazes, respectively. PMID- 27180221 TI - Performance tests of a large volume cerium tribromide (CeBr3) scintillation detector. AB - The response of a large cylindrical 76mm*76mm (height*diameter) cerium tribromide (CeBr3) detector was measured for prompt gamma rays. The total intrinsic activity of the CeBr3 detector, which was measured over 0.33-3.33MeV range, was found to be 0.022+/-0.001 counts/s/cm(3). The partial intrinsic activity ( due to (227)Ac contamination), was measured over a energy range of 1.22-2.20MeV energy, was found to be 0.007+/-0.001 counts/s/cm(3). Compared to intrinsic activities of LaBr3:Ce and LaCl3:Ce detectors of equivalent volume, the CeBr3 detector has 7-8 times less total intrinsic activity. The detector response for low energy prompt gamma rays was measured over 0.3-0.6MeVgamma energy range using a portable neutron generator-based Prompt Gamma Neutron Activation Analysis (PGNAA) setup. The experimental yield of boron, cadmium and mercury prompt gamma-rays was measured from water samples contaminated with 0.75-2.5wt% mercury, 0.31-2.50wt% boron, and 0.0625-0.500wt% cadmium, respectively. An excellent agreement has been observed between the calculated and experimental yields of the gamma rays. Also minimum detection limit (MDC) of the CeBr3 detector was measured for boron, cadmium and mercury samples. The CeBr3 detector has 23% smaller value of MDCB and 18% larger value of MDCCd than those of a LaBr3:Ce detector of equivalent size. This study has shown that CeBr3 detector has an excellent response for the low energy prompt gamma-rays with almost an order of magnitude low intrinsic activity as compared to LaCl3:Ce and LaBr3:Ce detectors of equivalent volume. PMID- 27180222 TI - The role of matrix metalloproteinases in muscle and adipose tissue development and meat quality: A review. AB - Matrix metalloproteinases (MMPs) are a group of enzymes that degrade extracellular matrix components but are also important signaling molecules that regulate many biological processes including muscle, adipose and connective tissue development. Most recently it has been discovered that MMPs act as intracellular signaling molecules inducing gene expression and altering related proteins in the nucleus. Several single nucleotide polymorphisms of MMPs and their inhibitors are known to exist and most of the research on MMPs to date has focused on their activity in relation to human health and disease. Nevertheless there is a growing body of evidence identifying important roles of MMPs as regulators of myogenesis, fibrogenesis and adipogenesis. The aim of this review is to highlight the currently known functions of the MMPs that have a direct bearing on the deposition of meat components and their relationship with meat quality. Some central pathways by which these enzymes can affect the tenderness, the amount and type of fatty acids are highlighted. PMID- 27180223 TI - Effect of MAP, vacuum skin-pack and combined packaging methods on physicochemical properties of beef steaks stored up to 12days. AB - The physicochemical properties of M. longissimus lumborum steaks over 12days of storage at 2 degrees C, and under three packaging conditions, were investigated: vacuum skin packaging (VSP); modified atmosphere packaging (MAP), and their combination with semi-permeable inner VSP film (VSP-MAP). Standard gas composition (80% O2/20% CO2) was used for MAP and VSP-MAP packaging. CIE L*a*b* color parameters of VSP-MAP samples were similar to those kept in MAP and significantly higher to those stored in VSP. Myoglobin oxidation was more evident in VSP-MAP and MAP samples than in VSP indicating increased oxidation processes. However, storage in MAP resulted in greater lipid oxidation compared both to VSP and VSP-MAP. No differences between treatments were observed in terms of Warner Bratzler shear force values and drip loss. In general, these results suggest that the combination of VSP and MAP methods may be an efficient way to reduce negative quality changes typical for both systems used separately. PMID- 27180224 TI - Cosmetic Appearance of Port-site Scars 1 Year After Laparoscopic Versus Robotic Sacrocolpopexy: A Supplementary Study of the ACCESS Clinical Trial. AB - STUDY OBJECTIVE: To prospectively measure trocar site appearances 1 year after surgery in women participants in the Abdominal Colpopexy: Comparison of Endoscopic Surgical Strategies Trial, a 2-center randomized surgical trial (NCT01124916). DESIGN: Supplementary analysis of a surgical trial that randomized women to robotic or laparoscopic sacrocolpopexy (Canadian Task Force classification I). SETTING: Operative trial. PATIENTS: Women undergoing clinically indicated sacrocolpopexy for symptomatic stage >=II pelvic organ prolapse were randomized to laparoscopic abdominal sacrocolpopexy (LASC) or robotic abdominal sacrocolpopexy (RASC). Trocar skin incision closure was standardized by using Dermabond (Ethicon, Somerville, NJ). MEASUREMENTS AND MAIN RESULTS: Photographs of all incision sites were taken at baseline (immediately), 6 weeks, 6 months, and 1 year after surgery. Study coordinators scored each incision with the validated Stony Brook Evaluation Scale (SBES), a 5-point wound evaluation scale. We calculated the average of all scars scores per case to determine the percent of optimal wound healing (0%-100%) for each case as well as the proportion of cases meeting 100% wound repair scoring. Wound repair scores across groups were tested with the Wilcoxon rank sum test. The overall proportion of cases in each group meeting "optimal" wound recovery (scores of 100%) was tested with the Fisher exact test. Seventy-eight women with a mean age of 59 years (range, 26-79 years) were randomized to LASC (n = 38) or RASC (n = 40). We did not detect significant differences in baseline characteristics or rates of dropout between the 2 study groups (5 in LASC and 7 in RASC, p = .60). Pain in the initial postoperative period was higher in the robotic arm although groups were similar at 2 weeks. Nearly all cases (75/78) contributed wound repair data (36 laparoscopic and 39 robotic). Laparoscopic surgeries require significantly fewer incisions (median = 4; range, 4-6) than robotic surgeries (median = 5; range, 4-6; p < .001). SBES scores at 6 weeks were not different for LASC and RASC (p = .426). By 6 months, the scores were better in the LASC group (84.8% +/- 8.8% vs 78.5% +/- 7.2%, p = .031), and this finding remained at 1 year (93.4% +/- 7.2% vs 85.9% +/- 8.8%, p = .001). The proportion of cases with optimal wound repair (score of 100%) was higher in the laparoscopic arm at 1 year after surgery (12/27 vs 4/33, p = .008). INTERVENTIONS: Women were randomized to robotic assisted laparoscopy or laparoscopy. CONCLUSION: Wound appearance using the SBES was better in the LASC group, suggesting that there may be alterations in the mechanism for wound initiation and/or healing based on the minimally invasive route used for sacrocolpopexy. PMID- 27180226 TI - Neuroprotective effects of p-tyrosol after the global cerebral ischemia in rats. AB - BACKGROUND: Salidroside is a biologically active compound derived from Rhodiola rosea L. Studies showed that salidroside after i.v. injection is extensively metabolized to p-tyrosol and only trace amounts of salidroside are found in the brain tissue. OBJECTIVE: The aim of the study was to investigate the neuroprotective effects of p-tyrosol in the global cerebral ischemia-reperfusion (GCI) model. STUDY DESIGN: A total of 103 Wistar rats were assigned to groups of sham-operated (n=10), control (n=42), p-tyrosol-treated (n=36), and pentoxifylline-treated (n=15) animals. The rats of control, p-tyrosol-treated, and pentoxifylline-treated groups received intravenously 0.9% NaCl solution, 2% solution of p-tyrosol in doses of 5mg/kg, 10mg/kg, and 20mg/kg, and pentoxifylline in a dose of 100mg/kg, respectively, daily for 5 days. Rats were examined at days 1, 3, and 5 after GCI. After evaluation of neurological deficit, animals were euthanized for morphological and biochemical characterization. METHODS: Rats of control, p-tyrosol-treated, and pentoxifylline-treated groups were exposed to three-vessel model of GCI. Neurological deficit, numeric density of neurons in hippocampal CA1 region, and percentage of neurons with focal and total chromatolysis were studied. Biochemical study assessed contents of conjugated dienes and fluorescent products in brain homogenate. RESULTS: In control group, only 50.0% of rats survived by day 5 after the GCI; 38.1% of survived animals had severe neurologic deficit. In brain tissue of PTX-treated rats, the levels of diene conjugates and fluorescent products were 79% and 73%, respectivley, at day 5 compared with control. Differences in diene conjugates were statistically significant compared with control. The survival rate of animals treated with 20mg/kg p-tyrosol was 82.3% at day 5 after GCI. In p-tyrosol treated GCI rats, the numeric density of neurons in the hippocampal CA1 region was higher by 31% compared with control. The percentage of neurons with focal and total chromatolysis decreased by 27% and 43%, respectively. At day 5 after GCI, the levels of conjugated dienes and fluorescent products were significantly lower (by 37% and 45%, respectively) in group of animals treated with 20mg/kg p-tyrosol compared with control. Moderate neuroprotective effects of 5mg/kg p-tyrosol administration were documented only at day 5 after GCI. In case of 10mg/kg p tyrosol administration, neuroprotection was documented sooner: at day 1 or 3 after GCI. However, administration of 5 and 10mg/kg p-tyrosol did not affect animal survival. CONCLUSION: Course administration of intravenous p-tyrosol in a dose of 20mg/kg increased survival, reduced neurological deficit after GCI, attenuated neuronal damage in the hippocampus, and attenuated lipid peroxidation in brain tissue in animals subject to GCI with reperfusion. PMID- 27180225 TI - Zika Virus Infection during Pregnancy in Mice Causes Placental Damage and Fetal Demise. AB - Zika virus (ZIKV) infection in pregnant women causes intrauterine growth restriction, spontaneous abortion, and microcephaly. Here, we describe two mouse models of placental and fetal disease associated with in utero transmission of ZIKV. Female mice lacking type I interferon signaling (Ifnar1(-/-)) crossed to wild-type (WT) males produced heterozygous fetuses resembling the immune status of human fetuses. Maternal inoculation at embryonic day 6.5 (E6.5) or E7.5 resulted in fetal demise that was associated with ZIKV infection of the placenta and fetal brain. We identified ZIKV within trophoblasts of the maternal and fetal placenta, consistent with a trans-placental infection route. Antibody blockade of Ifnar1 signaling in WT pregnant mice enhanced ZIKV trans-placental infection although it did not result in fetal death. These models will facilitate the study of ZIKV pathogenesis, in utero transmission, and testing of therapies and vaccines to prevent congenital malformations. PMID- 27180228 TI - Empyema necessitans caused by actinomycosis: A case report. AB - INTRODUCTION: Pulmonary actinomycosis is an uncommon clinical entity that the practicing thoracic surgeon rarely encounters. Empyema necessitans represents an even less common presentation of this pathology, and the often indolent disease course leads to early misdiagnosis in many cases. Familiarity with the varied presentations and possible operative strategies is essential to obtaining successful outcomes. PRESENTATION OF CASE: A 56-year-old male presented with swelling and pain over the lateral chest wall. Initial imaging studies demonstrated a mass concerning for infection vs. neoplasia. Further studies were obtained to confirm the diagnosis, with rapid progression of the mass. Surgical exploration with aggressive debridement of the chest wall without thoracotomy was performed. Actinomyces was identified on final pathology, confirming the diagnosis of Actinomycosis empyema necessitans. DISCUSSION: Traditional management strategies often involve pulmonary resection in addition to extended duration antimicrobial therapy. This report describes the uncommon clinical presentation and successful management of actinomycosis empyema necessitans with early limited operative intervention. CONCLUSION: In the event of minimal pulmonary involvement and absence of lung abscess, as was seen in this case, a thoracotomy with pulmonary resection can be avoided, and antibiotic duration limited. PMID- 27180227 TI - Monitoring of newborns at high risk for brain injury. AB - Due to the increasing number of surviving preterm newborns and to the recognition of therapeutic hypothermia as the current gold standard in newborns with hypoxic ischaemic encephalopathy, there has been a growing interest in the implementation of brain monitoring tools in newborns at high risk for neurological disorders.Among the most frequent neurological conditions and presentations in the neonatal period, neonatal seizures and neonatal status epilepticus, paroxysmal non-epileptic motor phenomena, hypoxic-ischaemic encephalopathy, white matter injury of prematurity and stroke require specific approaches to diagnosis. In this review we will describe the characteristics, aims, indications and limitations of routinely available diagnostic techniques such as conventional and amplitude-integrated EEG, evoked potentials, cranial ultrasound and brain MRI. We will conclude by briefly outlining potential future perspectives from research studies. PMID- 27180229 TI - Conservative treatment of hepatic portal venous gas consecutive to a complicated diverticulitis: A case report and literature review. AB - INTRODUCTION AND PRESENTATION OF CASE: Eight days after being diagnosed with multiple small strokes a 71year old male patient is readmitted with suspicion of a petit mal seizure also complained of diarrhoea and abdominal pain. The patient was stable, not febrile and neurologically intact with a slight tenderness in the left lower quadrant. An ultrasound revealed presence of air in the hepatic portal venous system and a suspicion for sigmoid diverticulitis. A CT-scan confirmed both diagnoses. We proceeded with a conservative regimen under close observation. The clinical course and laboratory results were unremarkable. DISCUSSION: The review of the literature (PubMed database) triggered 685 items with only one clinical trial establishing a scoring system to detect adult individuals, which need operation. CONCLUSION: A pneumoportogram (hepatic portal venous gas, HPVG) is a very rare and usually associated with bowel ischemia and from poor prognosis. The last decades saw the emergence of numerous other aetiologies (also benign) with a shift of paradigm from systematic emergency laparotomies to individual patient selection. PMID- 27180230 TI - Impact of serotype and sequence type on the preferential aerosolization of Streptococcus suis. AB - BACKGROUND: Streptococcus suis is a swine pathogen that causes pneumonia, septicemia and meningitis. It is also an important zoonotic agent responsible of several outbreaks in China. S. suis strains are classified into 35 serotypes based on the composition of their polysaccharide capsule. S. suis serotype 2 causes the majority of severe infections in pigs and in human, and can be further subdivided into sequence types (STs) based on multilocus sequence typing. The ST1 is associated with highly virulent strains. In North America, the strains most commonly isolated belong to ST25 and ST28, which are respectively moderately and weakly virulent in a mouse model. The presence of S. suis bioaerosols in the air of swine confinement buildings has been previously demonstrated. The aim of this study was to better understand the aerosolization behaviour of S. suis by investigating the preferential aerosolization of various strains of S. suis, belonging to different serotypes or STs, using in-house developed environmental chamber and bubble-burst nebulizer. qPCR technology was used to analyze the ratio of S. suis strains. RESULTS: The results suggest that the highly virulent serotype 2 ST1 strains are preferentially aerosolized and that the S. suis preferential aerosolization is a strain-dependent process. CONCLUSION: These observations will need to be confirmed using a larger number of strains. This study is a proof of concept and increases our knowledge on the potential aerosol transmission of S. suis. PMID- 27180231 TI - Identifying and ranking implicit leadership strategies to promote evidence-based practice implementation in addiction health services. AB - BACKGROUND: Despite a solid research base supporting evidence-based practices (EBPs) for addiction treatment such as contingency management and medication assisted treatment, these services are rarely implemented and delivered in community-based addiction treatment programs in the USA. As a result, many clients do not benefit from the most current and efficacious treatments, resulting in reduced quality of care and compromised treatment outcomes. Previous research indicates that addiction program leaders play a key role in supporting EBP adoption and use. The present study expanded on this previous work to identify strategies that addiction treatment program leaders report using to implement new practices. METHODS: We relied on a staged and iterative mixed methods approach to achieve the following four goals: (a) collect data using focus groups and semistructured interviews and conduct analyses to identify implicit managerial strategies for implementation, (b) use surveys to quantitatively rank strategy effectiveness, (c) determine how strategies fit with existing theories of organizational management and change, and (d) use a consensus group to corroborate and expand on the results of the previous three stages. Each goal corresponded to a methodological phase, which included data collection and analytic approaches to identify and evaluate leadership interventions that facilitate EBP implementation in community-based addiction treatment programs. RESULTS: Findings show that the top-ranked strategies involved the recruitment and selection of staff members receptive to change, offering support and requesting feedback during the implementation process, and offering in vivo and hands-on training. Most strategies corresponded to emergent implementation leadership approaches that also utilize principles of transformational and transactional leadership styles. Leadership behaviors represented orientations such as being proactive to respond to implementation needs, supportive to assist staff members during the uptake of new practices, knowledgeable to properly guide the implementation process, and perseverant to address ongoing barriers that are likely to stall implementation efforts. CONCLUSIONS: These findings emphasize how leadership approaches are leveraged to facilitate the implementation and delivery of EBPs in publicly funded addiction treatment programs. Findings have implications for the content and structure of leadership interventions needed in community-based addiction treatment programs and the development of leadership interventions in these and other service settings. PMID- 27180232 TI - Choice, Transparency, Coordination, and Quality Among Direct-to-Consumer Telemedicine Websites and Apps Treating Skin Disease. AB - IMPORTANCE: Evidence supports use of teleconsultation for improving patient access to dermatology. However, little is known about the quality of rapidly expanding direct-to-consumer (DTC) telemedicine websites and smartphone apps diagnosing and treating skin disease. OBJECTIVE: To assess the performance of DTC teledermatology services. DESIGN AND PARTICIPANTS: Simulated patients submitted a series of structured dermatologic cases with photographs, including neoplastic, inflammatory, and infectious conditions, using regional and national DTC telemedicine websites and smartphone apps offering services to California residents. MAIN OUTCOMES AND MEASURES: Choice of clinician, transparency of credentials, clinician location, demographic and medical data requested, diagnoses given, treatments recommended or prescribed, adverse effects discussed, care coordination. RESULTS: We received responses for 62 clinical encounters from 16 DTC telemedicine websites from February 4 to March 11, 2016. None asked for identification or raised concerns about pseudonym use or falsified photographs. During most encounters (42 [68%]), patients were assigned a clinician without any choice. Only 16 (26%) disclosed information about clinician licensure, and some used internationally based physicians without California licenses. Few collected the name of an existing primary care physician (14 [23%]) or offered to send records (6 [10%]). A diagnosis or likely diagnosis was proffered in 48 encounters (77%). Prescription medications were ordered in 31 of 48 diagnosed cases (65%), and relevant adverse effects or pregnancy risks were disclosed in a minority (10 of 31 [32%] and 6 of 14 [43%], respectively). Websites made several correct diagnoses in clinical scenarios where photographs alone were adequate, but when basic additional history elements (eg, fever, hypertrichosis, oligomenorrhea) were important, they regularly failed to ask simple relevant questions and diagnostic performance was poor. Major diagnoses were repeatedly missed, including secondary syphilis, eczema herpeticum, gram-negative folliculitis, and polycystic ovarian syndrome. Regardless of the diagnoses given, treatments prescribed were sometimes at odds with existing guidelines. CONCLUSIONS AND RELEVANCE: Telemedicine has potential to expand access to high-value health care. Our findings, however, raise concerns about the quality of skin disease diagnosis and treatment provided by many DTC telemedicine websites. Ongoing expansion of health plan coverage of these services may be premature. Until improvements are made, patients risk using health care services that lack transparency, choice, thoroughness, diagnostic and therapeutic quality, and care coordination. We offer several suggestions to improve the quality of DTC telemedicine websites and apps and avoid further growth of fragmented, low-quality care. PMID- 27180233 TI - Nail disorders in older people, and aspects of their pharmaceutical treatment. AB - The aim of this paper was to explore how aging influences the nail unit, its disorders and its response to treatment, and to identify some of the age-related gaps in the ungual drug delivery literature. Aging causes obvious changes to the nail, some of which are inherently due to old age, while others are due to diseases/conditions which become more prevalent as we age. Alterations in the nail plate's colour, contour, thickness, fragility, surface features, cell size, chemical composition and growth rate are some of the changes, with toenails and fingernails showing different effects. With respect to disease, the incidence of onychomycosis - the most common nail disorder - is considerably higher in older people. Similarly, brittle nails become more common as we age. In contrast, the literature about aging and the incidence of nail psoriasis is inconclusive, although, it is clear that as one gets older, the negative impact of nail psoriasis on one's quality of life decreases. Pharmaceutical treatment of the diseases comprises local and systemic therapies, sometimes in combination. Systemic therapies have the inherent disadvantages of adverse systemic effects, drug interactions and the need for monitoring, disadvantages which are especially problematic for older people who are more likely to suffer from co-morbidities and be on other medications. Topical therapy avoids such disadvantages. However, the success rates of commercially available preparations are low, and older people may need help with their application. It is also proposed that regular inspection and grooming of nails should become part of routine care of older people, as these would provide opportunities to identify and treat any problems at an earlier stage. PMID- 27180234 TI - Do surface-based match solution-based techniques? The case of drug-liposome interaction. AB - The aim of the study is to check if the information about drug/liposome interactions provided by Surface Plasmon Resonance (SPR) is comparable with that provided by potentiometry in which liposomes are not immobilized on a solid support. To reach our aim we apply QSPR and BR analysis to data extracted from the literature and carefully inspected for their reliability. Results show that log KD (SPR) is governed by a different balance of intermolecular interactions than log Dlip (potentiometry). PMID- 27180236 TI - A cost and performance comparison of Public Private Partnership and public hospitals in Spain. AB - Public-private partnership (PPP) initiatives are extending around the world, especially in Europe, as an innovation to traditional public health systems, with the intention of making them more efficient.There is a varied range of PPP models with different degrees of responsibility from simple public sector contracts with the private, up to the complete privatisation of the service. As such, we may say the involvement of the private sector embraces the development, financing and provision of public infrastructures and delivery services.In this paper, one of the oldest PPP initiatives developed in Spain and transferred to other European and Latin American countries is evaluated for first time: the integrated healthcare delivery Alzira model.Through a comparison of public and PPP hospital performance, cost and quality indicators, the efficiency of the PPP experience in five hospitals is evaluated to identify the influence of private management in the results.Regarding the performance and efficiency analysis, it is seen that the PPP group obtains good results, above the average, but not always better than those directly managed. It is necessary to conduct studies with a greater number of PPP hospitals to obtain conclusive results. PMID- 27180235 TI - Fabrication and development of artificial osteochondral constructs based on cancellous bone/hydrogel hybrid scaffold. AB - Using tissue engineering techniques, an artificial osteochondral construct was successfully fabricated to treat large osteochondral defects. In this study, porcine cancellous bones and chitosan/gelatin hydrogel scaffolds were used as substitutes to mimic bone and cartilage, respectively. The porosity and distribution of pore size in porcine bone was measured and the degradation ratio and swelling ratio for chitosan/gelatin hydrogel scaffolds was also determined in vitro. Surface morphology was analyzed with the scanning electron microscope (SEM). The physicochemical properties and the composition were tested by using an infrared instrument. A double layer composite scaffold was constructed via seeding adipose-derived stem cells (ADSCs) induced to chondrocytes and osteoblasts, followed by inoculation in cancellous bones and hydrogel scaffolds. Cell proliferation was assessed through Dead/Live staining and cellular activity was analyzed with IpWin5 software. Cell growth, adhesion and formation of extracellular matrix in composite scaffolds blank cancellous bones or hydrogel scaffolds were also analyzed. SEM analysis revealed a super porous internal structure of cancellous bone scaffolds and pore size was measured at an average of 410 +/- 59 MUm while porosity was recorded at 70.6 +/- 1.7 %. In the hydrogel scaffold, the average pore size was measured at 117 +/- 21 MUm and the porosity and swelling rate were recorded at 83.4 +/- 0.8 % and 362.0 +/- 2.4 %, respectively. Furthermore, the remaining hydrogel weighed 80.76 +/- 1.6 % of the original dry weight after hydration in PBS for 6 weeks. In summary, the cancellous bone and hydrogel composite scaffold is a promising biomaterial which shows an essential physical performance and strength with excellent osteochondral tissue interaction in situ. ADSCs are a suitable cell source for osteochondral composite reconstruction. Moreover, the bi-layered scaffold significantly enhanced cell proliferation compared to the cells seeded on either single scaffold. Therefore, a bi-layered composite scaffold is an appropriate candidate for fabrication of osteochondral tissue. PMID- 27180237 TI - Career as Affective Journey: How Constant Flux Challenges the Search for Career Pathways and Counseling. AB - Individuals have to actively manage their careers and with it their identities in this life domain. With the help of empirical findings and field reports, we will show how these changing demands need to be negotiated as part of identity development and, thus, career counseling processes. While Dialogical Self Theory (DST) is used to describe the constant negotiation of the self (identity) including dialogues within the person as well as dialogues with others, the Trajectory Equifinality Model (TEM) will help depict the development of career pathways that result from both - with a special focus on affective linking. Based on DST and TEM, it is argued that finding the right career is an ongoing and affective process and with that a developmental phenomenon that can be supported by different means: typologies that relate the individual to a larger population as well as idiographic approaches. PMID- 27180238 TI - Sedation at the end of life - a nation-wide study in palliative care units in Austria. AB - BACKGROUND: Sedation is used to an increasing extent in end-of-life care. Definitions and indications in this field are based on expert opinions and case series. Little is known about this practice at palliative care units in Austria. METHODS: Patients who died in Austrian palliative care units between June 2012 and June 2013 were identified. A predefined set of baseline characteristics and information on sedation during the last two weeks before death were obtained by reviewing the patients' charts. RESULTS: The data of 2414 patients from 23 palliative care units were available for analysis. Five hundred two (21 %) patients received sedation in the last two weeks preceding their death, 356 (71 %) received continuous sedation until death, and 119 (24 %) received intermittent sedation. The median duration of sedation was 48 h (IQR 10-72 h); 168 patients (34 %) were sedated for less than 24 h. Indications for sedation were delirium (51 %), existential distress (32 %), dyspnea (30 %), and pain (20 %). Midazolam was the most frequently used drug (79 %), followed by lorazepam (13 %), and haloperidol (10 %). Sedated patients were significantly younger (median age 67 years vs. 74 years, p <= 0.001, r = 0.22), suffered more often from an oncological disease (92 % vs. 82 %, p <= 0.001, phi = 0.107), and were hospitalized more frequently (94 % vs. 76 %, p <= 0.001, phi = 0.175). The median number of days between admission to a palliative care ward/mobile palliative care team and death did not differ significantly in sedated versus non-sedated patients (10 vs. 9 days; p = 0.491). CONCLUSION: This study provides insights into the practice of end-of-life sedation in Austria. Critical appraisal of these data will serve as a starting point for the development of nation-wide guidelines for palliative sedation in Austria. PMID- 27180239 TI - Obaculactone protects against bleomycin-induced pulmonary fibrosis in mice. AB - Idiopathic pulmonary fibrosis is a progressive, degenerative and almost irreversible disease. There is hardly an effective cure for lung damage due to pulmonary fibrosis. The purpose of this study was to evaluate the role of obaculactone in an already-assessed model of idiopathic pulmonary fibrosis induced by bleomycin administration. Mice were subjected to intratracheal instillation of bleomycin, and obaculactone was given orally after bleomycin instillation daily for 23days. Treatment with obaculactone ameliorated body weight loss, lung histopathology abnormalities and pulmonary collagen deposition, with a decrease of the inflammatory cell number and the cytokine level in bronchoalveolar lavage fluid. Moreover, obaculactone inhibited the expression of icam1, vcam1, inos and cox2, and attenuated oxidative stress in bleomycin-treated lungs. Importantly, the production of collagen I and alpha-SMA in lung tissues as well as the levels of TGF-beta1, ALK5, p-Smad2 and p-Smad3 in lung homogenates was also reduced after obaculactone treatment. Finally, the TGF-beta1-induced epithelial-mesenchymal transition via Smad-dependent and Smad-independent pathways was reversed by obaculactone. Collectively, these data suggest that obaculactone may be a promising drug candidate for the treatment of idiopathic pulmonary fibrosis. PMID- 27180240 TI - Activation of the Constitutive Androstane Receptor induces hepatic lipogenesis and regulates Pnpla3 gene expression in a LXR-independent way. AB - The Constitutive Androstane Receptor (CAR, NR1I3) has been newly described as a regulator of energy metabolism. A relevant number of studies using animal models of obesity suggest that CAR activation could be beneficial on the metabolic balance. However, this remains controversial and the underlying mechanisms are still unknown. This work aimed to investigate the effect of CAR activation on hepatic energy metabolism during physiological conditions, i.e. in mouse models not subjected to metabolic/nutritional stress. Gene expression profiling in the liver of CAR knockout and control mice on chow diet and treated with a CAR agonist highlighted CAR-mediated up-regulations of lipogenic genes, concomitant with neutral lipid accumulation. A strong CAR-mediated up-regulation of the patatin-like phospholipase domain-containing protein 3 (Pnpla3) was demonstrated. Pnpla3 is a gene whose polymorphism is associated with the pathogenesis of nonalcoholic fatty liver disease (NAFLD) development. This observation was confirmed in human hepatocytes treated with the antiepileptic drug and CAR activator, phenobarbital and in immortalized human hepatocytes treated with CITCO. Studying the molecular mechanisms controlling Pnpla3 gene expression, we demonstrated that CAR does not act by a direct regulation of Pnpla3 transcription or via the Liver X Receptor but may rather involve the transcription factor Carbohydrate Responsive Element-binding protein. These data provide new insights into the regulation by CAR of glycolytic and lipogenic genes and on pathogenesis of steatosis. This also raises the question concerning the impact of drugs and environmental contaminants in lipid-associated metabolic diseases. PMID- 27180242 TI - Effectiveness of sequential intravenous-to-oral antibiotic switch therapy in hospitalized patients with gram-positive infection: the SEQUENCE cohort study. AB - Switching from intravenous to oral antibiotic therapy may improve inpatient management and reduce hospital stays and the complications of intravenous treatment. We aimed to assess the effectiveness of intravenous-to-oral antibiotic switch therapy and an early discharge algorithm in hospitalized patients with gram-positive infection. We performed a prospective cohort study with a retrospective comparison cohort, recruited from eight tertiary, acute-care Spanish referral hospitals. All patients included had culture-confirmed methicillin-resistant gram-positive infection, or methicillin-susceptible gram positive infection and beta-lactam allergy and had received intravenous treatment with glycopeptides, lipopeptides, or linezolid. The study comprised two cohorts: the prospective cohort to assess the effectiveness of a sequential intravenous-to oral antibiotic switch algorithm and early discharge, and a retrospective cohort in which the algorithm had not been applied, used as the comparator. A total of 247 evaluable patients were included; 115 in the prospective and 132 in the retrospective cohort. Forty-five retrospective patients (34 %) were not changed to oral antibiotics, and 87 (66 %) were changed to oral antibiotics without following the proposed algorithm. The duration of hospitalization was significantly shorter in the prospective cohort compared to the retrospective group that did not switch to oral drugs (16.7 +/- 18.7 vs 23 +/- 13.4 days, P < 0.001). No differences were observed regarding the incidence of catheter-related bacteraemia (4.4 % vs 2.6 %, P = 0.621). Our results suggest that an intravenous to-oral antibiotic switch strategy is effective for reducing the length of hospital stay in selected hospitalized patients with gram-positive infection. PMID- 27180241 TI - The trypanocidal benznidazole promotes adaptive response to oxidative injury: Involvement of the nuclear factor-erythroid 2-related factor-2 (Nrf2) and multidrug resistance associated protein 2 (MRP2). AB - Oxidative stress is a frequent cause underlying drug-induced hepatotoxicity. Benznidazole (BZL) is the only trypanocidal agent available for treatment of Chagas disease in endemic areas. Its use is associated with side effects, including increases in biomarkers of hepatotoxicity. However, BZL potential to cause oxidative stress has been poorly investigated. Here, we evaluated the effect of a pharmacologically relevant BZL concentration (200MUM) at different time points on redox status and the counteracting mechanisms in the human hepatic cell line HepG2. BZL increased reactive oxygen species (ROS) after 1 and 3h of exposure, returning to normality at 24h. Additionally, BZL increased glutathione peroxidase activity at 12h and the oxidized glutathione/total glutathione (GSSG/GSSG+GSH) ratio that reached a peak at 24h. Thus, an enhanced detoxification of peroxide and GSSG formation could account for ROS normalization. GSSG/GSSG+GSH returned to control values at 48h. Expression of the multidrug resistance-associated protein 2 (MRP2) and GSSG efflux via MRP2 were induced by BZL at 24 and 48h, explaining normalization of GSSG/GSSG+GSH. BZL activated the nuclear erythroid 2-related factor 2 (Nrf2), already shown to modulate MRP2 expression in response to oxidative stress. Nrf2 participation was confirmed using Nrf2-knockout mice in which MRP2 mRNA expression was not affected by BZL. In summary, we demonstrated a ROS increase by BZL in HepG2 cells and a glutathione peroxidase- and MRP2 driven counteracting mechanism, being Nrf2 a key modulator of this response. Our results could explain hepatic alterations associated with BZL therapy. PMID- 27180243 TI - Impact of Helicobacter pylori eradication on refractory thrombocytopenia in patients with chronic HCV awaiting antiviral therapy. AB - The possibility of delaying treatment of HCV due to severe thrombocytopenia is challenging. This study aimed to detect the prevalence of active helicobacter infection as a claimed cause of thrombocytopenia in a cohort of Egyptian patients with chronic active HCV awaiting combined anti-viral therapy. The study included 400 chronic HCV patients with thrombocytopenia. Laboratory investigations included liver function tests, real time quantitative PCR, reticulocytic count, ESR, ANA, bone marrow aspiration, measurement of anti-helicobacter antibodies, and helicobacter stool antigen. Positive cases for active H. pylori were given the standard triple therapy for 2 weeks. Helicobacter stool antigen was detected 4 weeks after termination of therapy and the change in platelet count was detected 1 month after eradication. A total of 248 out of 281 seropositive patients for H. pylori (88.3 %) showed positive stool antigen (p = 0.01). Eradication was achieved in 169 (68.1 %) patients with platelet mean count 114.9 +/- 18.8 * 10(3)/MUl with highly significant statistical difference from pretreatment value (49.7 +/- 9.2 * 10(3)/MUl, p = 0.000). Seventy-nine patients were resistant to conventional triple therapy and given a 7-day course of moxifloxacin-based therapy; 61 patients responded (77.1 %) with mean platelet improvement from 76.4 +/- 17.4 * 10(3)/MUl to 104.2 +/- 15.2 * 10(3)/MUl (p = 0.000). The non-responders showed no improvement in their platelet count (74.6 +/ 20.5 vs. 73.6 +/- 15.3 * 10(3)/ul, P = 0.5). Eradication of active H. pylori in HCV augments platelet count and enhances the early start of antiviral therapy. PMID- 27180244 TI - Deep sequencing approach for investigating infectious agents causing fever. AB - Acute undifferentiated fever (AUF) poses a diagnostic challenge due to the variety of possible aetiologies. While the majority of AUFs resolve spontaneously, some cases become prolonged and cause significant morbidity and mortality, necessitating improved diagnostic methods. This study evaluated the utility of deep sequencing in fever investigation. DNA and RNA were isolated from plasma/sera of AUF cases being investigated at Cairns Hospital in northern Australia, including eight control samples from patients with a confirmed diagnosis. Following isolation, DNA and RNA were bulk amplified and RNA was reverse transcribed to cDNA. The resulting DNA and cDNA amplicons were subjected to deep sequencing on an Illumina HiSeq 2000 platform. Bioinformatics analysis was performed using the program Kraken and the CLC assembly-alignment pipeline. The results were compared with the outcomes of clinical tests. We generated between 4 and 20 million reads per sample. The results of Kraken and CLC analyses concurred with diagnoses obtained by other means in 87.5 % (7/8) and 25 % (2/8) of control samples, respectively. Some plausible causes of fever were identified in ten patients who remained undiagnosed following routine hospital investigations, including Escherichia coli bacteraemia and scrub typhus that eluded conventional tests. Achromobacter xylosoxidans, Alteromonas macleodii and Enterobacteria phage were prevalent in all samples. A deep sequencing approach of patient plasma/serum samples led to the identification of aetiological agents putatively implicated in AUFs and enabled the study of microbial diversity in human blood. The application of this approach in hospital practice is currently limited by sequencing input requirements and complicated data analysis. PMID- 27180245 TI - Increased vaginal pH in Ugandan women: what does it indicate? AB - Abnormal vaginal flora (AVF), indicative of bacterial vaginosis (BV) and/or aerobic vaginitis (AV), amongst other abnormalities, is a risk factor for multiple complications in pregnant as well as non-pregnant women. Screening for such conditions could help prevent these complications. Can self-testing for increased vaginal pH reliably detect BV and other high-risk microflora types, and is this more accurate than performing Gram stain-based Nugent score when screening for high-risk microflora? A total of 344 women presenting at different outpatient clinics in Mulago Hospital and Mbuikwe Outpatient clinics in Kampala, Uganda, were asked to test themselves by introducing a gloved finger into the vagina and smearing it on a microscopy slide, on which a pH strip was attached. Self-assessed categories of normal (pH 3.6-4.4), intermediate (4.5-4.7) or high pH (>4.7) were compared with demographic and with centralised microscopic data, both in air-dried rehydrated wet mounts (Femicare), as well as in Gram-stained specimens (Nugent). AVF was present in 38 %, BV in 25 % and AV in 11 % of patients. High pH and AVF is correlated with human immunodeficiency virus (HIV), infertility, frequent sex, but not vaginal douching. Screening for raised pH detects 90 % of AVF cases, but would require testing over half of the population. As AV and non-infectious conditions are frequent in women with AVF and high pH, Nugent score alone is an insufficient technique to screen women for a high-risk vaginal microflora, especially in infertile and HIV-infected women. PMID- 27180246 TI - Streptococcus salivarius by nasal spray for recurrent otitis: how good is the evidence? PMID- 27180247 TI - The relationship between dorsolateral prefrontal activation and speech performance-based social anxiety using functional near infrared spectroscopy. AB - Functional near-infrared (fNIR) spectroscopy is a promising new technology that has demonstrated utility in the study of normal human cognition. We utilized fNIR spectroscopy to examine the effect of social anxiety and performance on hemodynamic activity in the dorsolateral prefrontal cortex (DLPFC). Socially phobic participants and non-clinical participants with varying levels of social anxiety completed a public speaking task in front of a small virtual audience while the DLPFC was being monitored by the fNIR device. The relationship between anxiety and both blood volume (BV) and deoxygenated hemoglobin (Hb) varied significantly as a function of speech performance, such that individuals with low social anxiety who performed well showed an increase in DLPFC activation relative to those who did not perform well. This result suggests that effortful thinking and/or efficient top-down inhibitory control may have been required to complete an impromptu speech task with good performance. In contrast, good performers who were highly socially anxious showed lower DLPFC activation relative to good performers who were low in social anxiety, suggesting autopilot thinking or less effortful thinking. In poor performers, slight increases in DLPFC activation were observed from low to highly anxious individuals, which may reflect a shift from effortless thinking to heightened self-focused attention. Heightened self-focused attention, poor inhibitory control resulting in excessive fear or anxiety, or low motivation may lower performance. These results suggest that there can be different underlying mechanisms in the brain that affect the level of speech performance in individuals with varying degrees of social anxiety. This study highlights the utility of the fNIR device in the assessment of changes in DLPFC in response to exposure to realistic phobic stimuli, and further supports the potential utility of this technology in the study of the neurophysiology of anxiety disorders. PMID- 27180249 TI - Sexual determination based on multidetector computed tomographic measurements of the second cervical vertebra in a contemporary Japanese population. AB - Accurate sex estimation is important in forensic investigation to determine the identity of unknown individuals. The aim of this study was to investigate the accuracy of sex assessment based on measurements of the second cervical vertebra (C2) using computed tomographic (CT) images in a Japanese population and to develop discriminant function formulae. The data were collected from 224 Japanese cadavers (112 male subjects, 112 female subjects) on which postmortem CT scanning and subsequent forensic autopsy were performed. Nine CT measurements of the C2 were performed for CT images of each subject. The measurements were assessed using descriptive statistics and discriminant function analyses (DFA). All of the measurements demonstrated significant sexual dimorphism. Multiple DFA with stepwise variable selection resulted in multivariable models; a five-variable model reached an accuracy rate of 92.9%. Our results suggest that metric analysis based on CT images of the C2 can accurately determine the sex from the human skeletal remains in a contemporary Japanese population and may be useful for sex estimation in forensic anthropology. PMID- 27180250 TI - A cadaveric study on mylohyoid herniation of the sublingual gland. AB - The purpose of this study was to document the presence of a sublingual gland (SLG) herniating inferiorly through the mylohyoid muscle into the submandibular area. A total of 100 half-heads of 50 adult Korean cadavers were enrolled in this study. The floor of the mouth was dissected from the neck, and mylohyoid muscle patency and position of the sublingual gland were evaluated. Demographic factors of the donor and characteristics of the herniation were evaluated. Herniation was found in 29 (58.0 %) of the 50 cadavers or 42 of the 100 half-heads. Herniation was more frequently observed in females than in males (p = 0.009). However, no laterality was observed. Classifying the location of SLG herniation from the midpoint of the mandible to the hyoid bone into 3 regions, 32 (63 %) of herniations were found in the anterior one-third. No ranula formation was observed. The size and weight of normal glands tended to be larger than those of herniated glands, but no statistical significance was observed. An SLG hernia is a very common condition and is more frequently observed in females. As such, SLG herniation should be considered when a submental neck mass is evaluated. PMID- 27180248 TI - Frames of reference and categorical/coordinate spatial relations in a "what was where" task. AB - The aim of this study was to explore how people use egocentric (i.e., with respect to their body) and allocentric (i.e., with respect to another element in the environment) references in combination with coordinate (metric) or categorical (abstract) spatial information to identify a target element. Participants were asked to memorize triads of 3D objects or 2D figures, and immediately or after a delay of 5 s, they had to verbally indicate what was the object/figure: (1) closest/farthest to them (egocentric coordinate task); (2) on their right/left (egocentric categorical task); (3) closest/farthest to another object/figure (allocentric coordinate task); (4) on the right/left of another object/figure (allocentric categorical task). Results showed that the use of 2D figures favored categorical judgments over the coordinate ones with either an egocentric or an allocentric reference frame, whereas the use of 3D objects specifically favored egocentric coordinate judgments rather than the allocentric ones. Furthermore, egocentric judgments were more accurate than allocentric judgments when the response was Immediate rather than delayed and 3D objects rather than 2D figures were used. This pattern of results is discussed in the light of the functional roles attributed to the frames of reference and spatial relations by relevant theories of visuospatial processing. PMID- 27180251 TI - Infective endocarditis of an aorto-right atrial fistula caused by asymptomatic rupture of a sinus of Valsalva aneurysm: a case report. AB - Asymptomatic rupture of a sinus of Valsalva aneurysm is rare. A fistula following rupture of a sinus of Valsalva aneurysm may cause infective endocarditis. Here, we report a case of infective endocarditis of an aorto-right atrial fistula caused by asymptomatic rupture of a sinus of Valsalva aneurysm. A 45-year-old male, who was first diagnosed with a heart murmur at the age of 37 years, presented with fever. Blood culture was positive for Streptococcus gordonii. Ultrasound echocardiography revealed an aorto-right atrial fistula caused by rupture of a sinus of Valsalva aneurysm. After the infective endocarditis was healed by antibiotics, we successfully performed surgical repair of the aorto right atrial fistula. Although asymptomatic rupture of a sinus of Valsalva aneurysm is uncommon, it should be recognized as a possible cause of infective endocarditis. PMID- 27180252 TI - Mining and characterization of two amidase signature family amidases from Brevibacterium epidermidis ZJB-07021 by an efficient genome mining approach. AB - Amidases have received increasing attention for their significant potential in the production of valuable carboxylic acids. In this study, two amidases belonging to amidase signature family (BeAmi2 and BeAmi4) were identified and mined from genomic DNA of Brevibacterium epidermidis ZJB-07021 by an efficient strategy combining comparative analysis of genomes and identification of unknown region by high-efficiency thermal asymmetric interlaced PCR (HiTAIL-PCR). The deduced amino acid sequences of BeAmi2 and BeAmi4 showed low identity (< 40%) with other reported amidases. The two amidases displayed optimum activity toward a wide spectrum of substrates at a mild alkaline pH and 45 degrees C. Both of them were remarkably inactivated by serine-directed inhibitor and sulfhydryl reducing agent. Kinetic analysis revealed that nicotinamide was the preferable substrate for both amidases and the chlorine substitutions on the pyridine ring had a negative effect on activity. The bioprocesses for hydrolysis of 100 mM nicotinamide, isonicotinamide, 2-chloronicotinamide and 5-chloronicotinamide with purified BeAmi2 (6 U mL(-1)) were complete in 60 min with full conversion except 2-chloronicotinamide. These results indicated BeAmi2 was an effective catalyst for hydrolysis of several nicotinamide derivatives. PMID- 27180253 TI - Adolescent knee pain and patellar dislocations are associated with patellofemoral osteoarthritis in adulthood: A case control study. AB - BACKGROUND: There is a lack of information about the association between patellofemoral osteoarthritis (PFOA) and both adolescent anterior knee pain (AKP) and previous patellar dislocations. METHODS: This case-control study involved 222 participants from our knee arthroplasty database answering a questionnaire. One hundred and eleven patients suffering from PFOA were 1:1 matched by gender with a unicompartmental tibiofemoral arthritis control group. Multivariate correlation and binary logistic regression analysis were performed, with odds ratios (ORs) and 95% confidence intervals (CIs) calculated. RESULTS: An individual is 7.5 times more likely to develop PFOA if they have suffered from adolescent AKP (OR 7.5, 95% CIs 1.51 to 36.94). Additionally, experiencing a patellar dislocation increases the likelihood of development of PFOA, with an adjusted odds ratio of 3.2 (95% CIs 1.25 to 8.18). A 44-year difference in median age of first dislocation was also observed between the groups. CONCLUSION: This should bring into question the traditional belief that adolescent anterior knee pain is a benign pathology. Patellar dislocation is also a significant risk factor. These patients merit investigation, we encourage clinical acknowledgement of the potential consequences when encountering patients suffering from anterior knee pain or patellar dislocation. PMID- 27180254 TI - Relationship between meniscal integrity and risk factors for cartilage degeneration. AB - BACKGROUND: The purpose of this study was to use MRI to determine if a loss of meniscal intra-substance integrity, as determined by T2* relaxation time, is associated with an increase of Kellgren-Lawrence (KL) grade, and if this was correlated with risk factors for cartilage degeneration, namely meniscal extrusion, contact area and anterior-posterior (AP) displacement. METHODS: Eleven symptomatic knees with a KL 2 to 4 and 11 control knees with a KL 0 to 1 were studied. A 3 Tesla MRI scanner was used to scan all knees at 15 degrees of flexion. With a 222N compression applied, a 3D SPACE sequence was obtained, followed by a spin echo 3D T2* mapping sequence. Next, an internal tibial torque of 5Nm was added and a second 3D SPACE sequence obtained. The MRI scans were post processed to evaluate meniscal extrusion, contact area, AP displacement and T2* relaxation time. RESULTS: KL grade was correlated with T2* relaxation time for both the anterior medial meniscus (r=0.79, p<0.001) and the posterior lateral meniscus (r=0.55, p=0.009). In addition, T2* relaxation time was found to be correlated with risk factors for cartilage degeneration. The largest increases in meniscal extrusion and decreases in contact area were noted for those with meniscal tears (KL 3 to 4). All patients with KL 3 to 4 indicated evidence of meniscal tears. CONCLUSIONS: This suggests that a loss of meniscal integrity, in the form of intra-substance degeneration, is correlated with risk factors for cartilage degeneration. PMID- 27180255 TI - Evaluation of meniscal extrusion with posterior root disruption and repair using ultrasound. AB - BACKGROUND: Ultrasound techniques have been utilized for detection of discrete meniscus tears and extrusion. Meniscal extrusion is associated with increased contact pressure and decreased contact area contributing to the advancement of knee osteoarthritis. The purpose of this biomechanical study was to detect meniscal extrusion using a clinically available, portable ultrasound device. And further, to show that extent of injury and a weight-bearing state correlate with amount of extrusion. METHODS: A portable, hand-held ultrasound was utilized to image the lateral meniscus in association with (1) an intact posterior root attachment, (2) a 50% cut, (3) a 100% cut, and (4) repaired posterior root attachment. Images were obtained in an unloaded condition, and again under a static, physiologic (70kg) axial load for above injury levels, and again following repair. RESULTS: Significant differences in extrusion were noted between the intact and both the 50% cut (p=0.028) and 100% cut groups (p<0.001) all in the loaded position. No significant difference was found in extrusion between intact state and repaired posterior root in the axially loaded position (p=0.174). Both load (p=0.003) and injury level (p=0.005) had significant effects on the mean extrusion of the lateral meniscus. CONCLUSION: Sectioning of the lateral meniscus posterior root will produce significantly increased lateral extrusion of the meniscus under physiologic loads. Unlike MRI evaluation, weight bearing ultrasound images allow a functional assessment of meniscus extrusion. Trans-tibial posterior root repair can restore the lateral meniscus position and integrity. CLINICAL RELEVANCE: This weight-bearing ultrasound technique can be an important assessment tool for complete evaluation of meniscus injuries. PMID- 27180256 TI - Parental acceptance and uptake of the HPV vaccine among African-Americans and Latinos in the United States: A literature review. AB - BACKGROUND: African-Americans and Latinos suffer the highest cervical cancer burden compared to other populations and have sub-optimal HPV vaccination rates. OBJECTIVE: To condense research findings of studies conducted with African Americans and Latinos on factors associated with HPV vaccine acceptability and uptake. METHODS: Standards for conducting an integrative review were used. PubMed, Cumulative Index to Nursing and Allied Health Literature, and PsycINFO databases were searched. RESULTS: Awareness about HPV and the HPV vaccine varied by demographics of parents. For Latino parents, acculturation and awareness were associated. However, findings were mixed regarding the association between acculturation and knowledge. Among African-Americans, higher socioeconomic status (SES) and awareness were associated. Sexuality-related concerns, concerns about safety and low perceived risk of daughter's acquiring HPV emerged as barriers to vaccination among Latinos and African-Americans. Among Latinos, vaccine acceptability was associated with the vaccine's cancer prevention benefits and a provider's recommendation. Among African-Americans, acceptability was associated with awareness, perceived risk of acquiring HPV, religion, and a provider's recommendation. Few interventions have been developed to increase HPV vaccine acceptance. Importantly, few studies assessed the influence of culture on vaccine acceptance and uptake. CONCLUSIONS: Future research should be informed by culture centered theories as this is the first step to inform the development of culturally-grounded interventions. PMID- 27180257 TI - A sign of the times: To have or to be? Social capital or social cohesion? AB - Among various social factors associated with health behavior and disease, social cohesion has not captured the imagination of public health researchers as much as social capital as evidenced by the subsuming of social cohesion into social capital and the numerous studies analyzing social capital and the comparatively fewer articles analyzing social cohesion and health. In this paper we provide a brief overview of the evolution of the conceptualization of social capital and social cohesion and we use philosopher Erich Fromm's distinction between "having" and "being" to understand the current research focus on capital over cohesion. We argue that social capital is related to having while social cohesion is related to being and that an emphasis on social capital leads to individualizing tendencies that are antithetical to cohesion. We provide examples drawn from the literature where this conflation of social capital and cohesion results in non concordant definitions and subsequent operationalization of these constructs. Beyond semantics, the practical implication of focusing on "having" vs. "being" include an emphasis on understanding how to normalize groups and populations rather than providing those groups space for empowerment and agency leading to health. PMID- 27180258 TI - Continuous intravenous infusion of enfuvirtide in a patient with a multidrug resistant HIV strain. AB - Case description To evaluate whether continuous intravenous (i.v.) administration of enfuvirtide (T20) could be a suitable alternative to subcutaneous (s.c.) administration of T20 in a patient with extensively drug-resistant HIV experiencing difficulties administering T20 subcutaneously. T20 was administered to a patient through 100 mL cassettes once daily via a CADD. Plasma samples were drawn and the pharmacokinetic profile compared to that of s.c. twice daily administration of T20. Also, viral replication and CD4+ count were monitored over a period of 9 months for this study. Continuous i.v. administration of T20 resulted in significantly higher T20 plasma levels compared to s.c. administration, continued viral suppression, a rise in CD4+ count and strong patient preference over s.c. administration. Conclusion This method of T20 administration may be a suitable alternative for selected patients who are not able to tolerate it when given subcutaneously. It may even be considered a priori in selected patients with extensive viral resistance who are unable or unwilling to inject T20 subcutaneously. PMID- 27180259 TI - Updated 2013 College of American Pathologists/American Society of Clinical Oncology (CAP/ASCO) guideline recommendations for human epidermal growth factor receptor 2 (HER2) fluorescent in situ hybridization (FISH) testing increase HER2 positive and HER2 equivocal breast cancer cases; retrospective study of HER2 FISH results of 836 invasive breast cancers. AB - For dual probe HER2 FISH assay, the 2013 CAP/ASCO guideline recommendations lowered the HER2/CEP17 ratio cut off for HER2 amplification to >=2.0 and introduced an average HER2 copy number criterion for HER2 amplification (>=6.0/cell) and HER2 equivocal categories (>=4 and <6/cell). The HER2/CEP17 equivocal category is eliminated. The aim of this study is to assess the impact of 2013 HER2 FISH testing guideline recommendations update on the assignment of HER2 status with dual probe HER2 FISH assay. Dual probe HER2 FISH assay results on breast cancers from 09/2009 to 07/2015 that underwent reflex HER2 FISH testing after equivocal HER2 (2+) immunohistochemistry (IHC) were reviewed. HER2 copy number, CEP17 signals, and HER2/CEP ratios were noted. HER2 status was assigned as HER2 negative (HER2-), HER2 equivocal (HER2e), and HER2 amplified (HER2+) by applying both 2007 and 2013 CAP/ASCO HER2 FISH guideline recommendations and results were compared. New guidelines reclassified HER2 FISH status in a significant proportion of cases (8.3 %, 69/836; p = .021). There were 22 (2.6 %) more HER2+, 17 (2.1 %) more HER2e, and 39 (4.1 %) fewer HER2- tumors. Change of HER2 status correlated significantly with >=3 CEP17 signals (38 vs. 2 %; p < .001). The 2013 CAP/ASCO guideline recommendations for HER2 FISH testing by dual probe assay increased the HER2 amplified and HER2 equivocal tumors. Increase in HER2 equivocal tumors would potentially increase the frequency of repeat HER2 testing. Tumors with >=3 CEP17 signals, so-called chromosome 17 polysomy, are more likely to be impacted and classified as HER2 equivocal. PMID- 27180260 TI - Intracellular sources of ornithine for polyamine synthesis in endothelial cells. AB - Polyamines are essential for proliferation of endothelial cells (EC) and angiogenesis. This study was conducted to identify the metabolic source(s) of ornithine for polyamine synthesis in EC, using N(omega)-hydroxy-nor-L-arginine (Nor-NOHA, an inhibitor of arginase) and gabaculine (an inhibitor of ornithine aminotransferase; OAT). Nor-NOHA inhibited arginase with an IC50 value of 10 uM for intact EC. Nor-NOHA (0.5 mM) alone inhibited arginase activity in EC by 98 %, increased total cellular concentrations of arginine by 14 %, and decreased total cellular concentrations of ornithine, putrescine and spermidine by 17, 65 and 74 %, respectively. Arginine and glutamine contributed to 73 and 26 % of the ornithine produced by EC, respectively. Gabaculine (1 mM) alone decreased the total cellular concentrations of arginine, ornithine, putrescine, and spermidine by 14, 96, 32, and 42 %, respectively. A combination of both Nor-NOHA and gabaculine completely blocked ornithine production in EC, resulting in no detectable cellular ornithine and almost complete depletion of cellular putrescine and spermidine. Addition of 0.5 mM ornithine restored the intracellular concentrations of polyamines in EC treated with Nor-NOHA plus gabaculine, indicating that Nor-NOHA and gabaculine did not inhibit ornithine decarboxylase activity. Our results suggest that the arginase and OAT pathways are the exclusive sources of ornithine in EC when there is little extracellular ornithine and that there is intracellular compartmentalization of arginine and ornithine for endothelial synthesis of polyamines. These novel findings may have important implications for improving placental vascular growth, wound healing, and cancer therapy. PMID- 27180261 TI - The role of miR-126 in embryonic angiogenesis, adult vascular homeostasis, and vascular repair and its alterations in atherosclerotic disease. AB - Expression of microRNA (miR)-126 is enriched in endothelial cells (ECs) and endothelial progenitor cells (EPCs). MiR-126 is considered a master regulator of physiological angiogenesis. In embryonic vasculogenesis, this miRNA is involved in induction of angiogenic signaling, supports differentiation of embryonic stem cells to EPCs and ECs, and promotes EC maturation. However, in mature ECs and adult EPCs, miR-126 contributes to vascular homeostasis by inhibiting angiogenesis and maintaining the quiescent endothelial phenotype associated with increased vascular integrity and inhibited proliferation and motility. In a case of vessel injury and/or hypoxia, miR-126 up-regulation activates EPCs and ECs and contributes to vascular healing and neovessel formation. Indeed, miR-126 exhibits vasculoprotective and atheroprotective properties. The promising regenerative and proangiogenic potential of this miRNA will be helpful for development of cardioprotective strategies and cardiovascular repair therapies of myocardial infarction, heart failure, and other cardiovascular pathology. PMID- 27180262 TI - Misexpression of Tbx18 in cardiac chambers of fetal mice interferes with chamber specific developmental programs but does not induce a pacemaker-like gene signature. AB - Initiation of cardiac excitation depends on a specialized group of cardiomyocytes at the venous pole of the heart, the sinoatrial node (SAN). The T-box transcription factor gene Tbx18 is expressed in the SAN myocardium and is required for formation of a large portion of the pacemaker. Previous studies suggested that Tbx18 is also sufficient to reprogram ventricular cardiomyocytes into SAN cells in rat, guinea-pig and pig hearts. To evaluate the consequences of misexpression of Tbx18 for imposing a nodal phenotype onto chamber myocardial cells in fetal mice, we used two independent conditional approaches with chamber specific cre driver lines and an Hprt(Tbx18) misexpression allele. Myh6 Cre/+;Hprt(Tbx18/y) mice developed dilated atria with thickened walls, reduced right ventricles and septal defects that resulted in reduced embryonic and post natal survival. Tagln-Cre/+;Hprt(Tbx18/y) mice exhibited slightly smaller hearts with rounded trabeculae that supported normal embryonic survival. Molecular analyses showed that the SAN gap junction and ion channel profile was not ectopically induced in chamber myocardium but the working myocardial gene program was partially inhibited in atria and ventricles of both misexpression models. Left atrial expression of Pitx2 was strongly repressed in Myh6 Cre/+;Hprt(Tbx18/y) embryos. We conclude that exclusion of Tbx18 expression from the developing atria and (right) ventricle is important to achieve normal cardiac left-right patterning and myocardial differentiation, and that Tbx18 is not sufficient to induce full SAN differentiation of chamber cardiomyocytes in fetal mice. PMID- 27180263 TI - Evaluation of leaf wetness duration models for operational use in strawberry disease-warning systems in four US states. AB - Leaf wetness duration (LWD) plays a key role in disease development and is often used as an input in disease-warning systems. LWD is often estimated using mathematical models, since measurement by sensors is rarely available and/or reliable. A strawberry disease-warning system called "Strawberry Advisory System" (SAS) is used by growers in Florida, USA, in deciding when to spray their strawberry fields to control anthracnose and Botrytis fruit rot. Currently, SAS is implemented at six locations, where reliable LWD sensors are deployed. A robust LWD model would facilitate SAS expansion from Florida to other regions where reliable LW sensors are not available. The objective of this study was to evaluate the use of mathematical models to estimate LWD and time of spray recommendations in comparison to on site LWD measurements. Specific objectives were to (i) compare model estimated and observed LWD and resulting differences in timing and number of fungicide spray recommendations, (ii) evaluate the effects of weather station sensors precision on LWD models performance, and (iii) compare LWD models performance across four states in the USA. The LWD models evaluated were the classification and regression tree (CART), dew point depression (DPD), number of hours with relative humidity equal or greater than 90 % (NHRH >=90 %), and Penman-Monteith (P-M). P-M model was expected to have the lowest errors, since it is a physically based and thus portable model. Indeed, the P-M model estimated LWD most accurately (MAE <2 h) at a weather station with high precision sensors but was the least accurate when lower precision sensors of relative humidity and estimated net radiation (based on solar radiation and temperature) were used (MAE = 3.7 h). The CART model was the most robust for estimating LWD and for advising growers on fungicide-spray timing for anthracnose and Botrytis fruit rot control and is therefore the model we recommend for expanding the strawberry disease warning beyond Florida, to other locations where weather stations may be deployed with lower precision sensors, and net radiation observations are not available. PMID- 27180264 TI - Twelve-month and sixty-month outcomes of noncultured cellular grafting for vitiligo. AB - BACKGROUND: Noncultured cellular grafting is a known surgical technique for vitiligo. OBJECTIVE: This study evaluated our center's 12-month repigmentation outcome and its maintenance up to 60 months, factors influencing repigmentation and safety data. METHODS: Clinicoepidemiologic and repigmentation data were reviewed for patients with vitiligo who had undergone noncultured cellular grafting from March 2006 to December 2012 at the National Skin Center, Singapore. RESULTS: All 177 patients who received noncultured cellular grafting during the study period were included. For those with available data, good to excellent repigmentation was present in 83% at 60 months. At 12 months, 88% of patients (n = 52) with segmental vitiligo achieved good to excellent repigmentation compared with 71% (n = 55) with nonsegmental vitiligo (P < .05). More patients on collagen dressings (82%) achieved good to excellent repigmentation compared with those who received hyaluronic acid (63%) (P < .05). Sites of lesions and postgrafting phototherapy did not significantly affect repigmentation outcome. Adverse reactions were uncommon and mild. LIMITATIONS: The study is limited by its retrospective nature, the progressive loss to follow-up of patients, the absence of blinding, and the lack of use of standardized assessment tools. CONCLUSION: Noncultured cellular grafting was successful in allowing more than 80% of patients to achieve good to excellent repigmentation for at least 60 months. PMID- 27180265 TI - TALEN-Mediated Homologous Recombination Produces Site-Directed DNA Base Change and Herbicide-Resistant Rice. AB - Over the last decades, much endeavor has been made to advance genome editing technology due to its promising role in both basic and synthetic biology. The breakthrough has been made in recent years with the advent of sequence-specific endonucleases, especially zinc finger nucleases (ZFNs), transcription activator like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPRs) guided nucleases (e.g., Cas9). In higher eukaryotic organisms, site-directed mutagenesis usually can be achieved through non homologous end-joining (NHEJ) repair to the DNA double-strand breaks (DSBs) caused by the exogenously applied nucleases. However, site-specific gene replacement or genuine genome editing through homologous recombination (HR) repair to DSBs remains a challenge. As a proof of concept gene replacement through TALEN-based HR in rice (Oryza sativa), we successfully produced double point mutations in rice acetolactate synthase gene (OsALS) and generated herbicide resistant rice lines by using TALENs and donor DNA carrying the desired mutations. After ballistic delivery into rice calli of TALEN construct and donor DNA, nine HR events with different genotypes of OsALS were obtained in T0 generation at the efficiency of 1.4%-6.3% from three experiments. The HR-mediated gene edits were heritable to the progeny of T1 generation. The edited T1 plants were as morphologically normal as the control plants while displayed strong herbicide resistance. The results demonstrate the feasibility of TALEN-mediated genome editing in rice and provide useful information for further genome editing by other nuclease-based genome editing platforms. PMID- 27180267 TI - Seasonal proliferation rates and the capacity to express genes involved in cell cycling and maintenance in response to seasonal and experimental food shortage in Laternula elliptica from King George Island. AB - Melting of coastal glaciers at the West Antarctic Peninsula (WAP) causes shorter winter sea ice duration, intensified ice scouring, sediment erosion and surface freshening in summer, which alters coastal productivity and feeding conditions for the benthos. The soft shell clam Laternula elliptica is a fast growing and abundant filter feeder in coastal Antarctica and a key element for bentho-pelagic carbon recycling. Our aim was to assess the cellular growth and maintenance capacity of small and large clams during natural winter food shortage (seasonal sampling) and in response to experimental starvation exposure. We measured tissue specific proliferation rates, the expression of cell cycling genes, and the iron binding protein Le-ferritin in freshly collected specimens in spring (Nov 2008) and at the end of summer (March 2009). For the experimental approach, we focused on 14 cell cycling and metabolic genes using the same animal size groups. Mantle tissue of young bivalves was the only tissue showing accelerated proliferation in summer (1.7% of cells dividing per day in March) compared to 0.4% dividing cells in animals collected in November. In mantle, siphon and adductor muscle proliferation rates were higher in younger compared to older individuals. At transcript level, Le-cyclin D was upregulated in digestive gland of older animals collected in spring (Nov) compared to March indicating initiation of cell proliferation. Likewise, during experimental starvation Le-cyclin D expression increased in large clam digestive gland, whereas Le-cyclin D and the autophagic factor beclin1 decreased in digestive gland of smaller starved clams. The paper corroborates earlier findings of size and age dependent differences in the metabolic response and gene expression patterns in L. elliptica under energetic deprivation. Age structure of shallow water populations can potentially change due to differences in cellular response between young and old animals as environmental stress levels increase. PMID- 27180266 TI - Prognostic significance of serum neuron-specific enolase in small cell carcinoma of the urinary bladder. AB - PURPOSE: Small cell carcinoma of the urinary bladder (SCCB) is known for its aggressive clinical features and poor prognosis. No prognostic factor has been established so far. The aim of this study was to assess the significance of possible prognostic factors, including serum neuron-specific enolase (NSE), an established biomarker for small cell lung carcinoma. METHODS: We retrospectively reviewed 31 patients with primary SCCB treated at our eight affiliate institutions between 2001 and 2014. The association of various clinicopathological factors at diagnosis, including the serum NSE value, with cancer-specific survival (CSS) was assessed. The log-rank test and Cox proportional hazards model were used for univariate and multivariate analyses, respectively. RESULTS: Nineteen (61.3 %) died of SCCB during the follow-up, with a median survival time of 12.7 months. Prognostic factors were analyzed for the 25 patients after excluding six with missing data. Univariate analysis demonstrated that stage (extensive disease) and serum NSE >=25 ng/ml were significantly associated with worse CSS. Multivariate analysis identified increased serum NSE value as a sole independent predictor of CSS (hazard ratio 18.52, p = 0.0022). CONCLUSIONS: Serum NSE value at diagnosis was an independent prognostic factor for primary SCCB and may serve as a useful biomarker in the management of SCCB. PMID- 27180268 TI - Synergistic effect of pacritinib with erlotinib on JAK2-mediated resistance in epidermal gowth factor receptor mutation-positive non-small cell lung Cancer. AB - The combination effect of pacritinib, a novel JAK2/FLT3 inhibitor, with erlotinib, the epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR TKI), on non-small cell lung cancer cells with EGFR activating mutations was investigated. The combination showed synergistic effects on JAK2-mediated EGFR TKI-resistant PC-9/ER3 cells in some cases. The combination markedly suppressed pAKT and pERK although pSTAT3 expression was similar regardless of treatment with the pacritinib, pacritinib + erlotinib, or control in PC-9/ER3 cells. Receptor tyrosine kinase array profiling demonstrated that pacritinib suppressed MET in the PC-9/ER3 cells. The combined treatment of pacritinib and erlotinib in PC 9/ER3 xenografts showed more tumor shrinkage compared with each drug as monotherapy. Western blotting revealed that pMET in tumor samples was inhibited. These results suggest MET suppression by pacritinib may play a role in overcoming the EGFR-TKI resistance mediated by JAK2 in the PC-9/ER3 cells. In conclusion, pacritinib combined with EGFR-TKI might be a potent strategy against JAK2 mediated EGFR-TKI resistance. PMID- 27180269 TI - Rapid detection and grouping of porcine bocaviruses by an EvaGreen((r)) based multiplex real-time PCR assay using melting curve analysis. AB - Several novel porcine bocaviruses (PBoVs) have been identified in pigs in recent years and association of these viruses with respiratory signs or diarrhea has been suggested. In this study, an EvaGreen((r))-based multiplex real-time PCR (EG mPCR) with melting curve analysis was developed for simultaneous detection and grouping of novel PBoVs into the same genogroups G1, G2 and G3. Each target produced a specific amplicon with a melting peak of 81.3 +/- 0.34 degrees C for PBoV G1, 78.2 +/- 0.37 degrees C for PBoV G2, and 85.0 +/- 0.29 degrees C for PBoV G3. Non-specific reactions were not observed when other pig viruses were used to assess the EG-mPCR assay. The sensitivity of the EG-mPCR assay using purified plasmid constructs containing the specific viral target fragments was 100 copies for PBoV G1, 50 for PBoV G2 and 100 for PBoV G3. The assay is able to detect and distinguish three PBoV groups with intra-assay and inter-assay variations ranging from 0.13 to 1.59%. The newly established EG-mPCR assay was validated with 227 field samples from pigs. PBoV G1, G2 and G3 was detected in 15.0%, 25.1% and 41.9% of the investigated samples and coinfections of two or three PBoV groups were also detected in 25.1% of the cases, indicating that all PBoV groups are prevalent in Chinese pigs. The agreement of the EG-mPCR assay with an EvaGreen-based singleplex real-time PCR (EG-sPCR) assay was 99.1%. This EG-mPCR will serve as a rapid, sensitive, reliable and cost effective alternative for routine surveillance testing of multiple PBoVs in pigs and will enhance our understanding of the epidemiological features and possible also pathogenetic changes associated with these viruses in pigs. PMID- 27180270 TI - In women with gestational diabetes mellitus factors influencing growth have a larger effect on placental weight than on birth weight. AB - BACKGROUND AND AIMS: Excessive fetal and placental growth are very common in diabetic pregnancy. We aimed to analyze in women with gestational diabetes mellitus (GDM) the association with birth weight (BW), placental weight (PW) and placental-to-birth weight (PWBW) ratio of acknowledged BW predictors. MATERIAL AND METHODS: We performed a retrospective analysis of a prospective cohort database from a tertiary hospital. Inclusion criteria were singleton pregnancy, diagnosis of GDM, delivery between 1982 and 2011 and gestational age at birth >=23 weeks. Multiple regression analysis was performed using as dependent variables BW, PW and PWBW ratio and as independent ones maternal characteristics at baseline, metabolic characteristics (GDM diagnosis, treatment, control), pregnancy-induced hypertension, gestational age at delivery and fetal sex. Two sensitivity analyses were performed. RESULTS: We evaluated 2547 women, PW being available in 85.3%. BW was 3260g (2976, 3575), PW 620g (540, 720) and PWBW ratio 19.27 (17.20, 21.47). Among the 24 analyzed variables, there was an important overlap among those associated with BW, PW and PWBW ratio. For most characteristics associated with both BW and PW, the magnitude of the association was greater for the latter, both when promoting growth (i.e. prepregnancy body mass index, 3h plasma glucose at diagnosis) and when restricting it (insulin treatment). CONCLUSION: We conclude that in women with GDM and singleton pregnancies, variables associated with BW, PW and PWBW ratio overlap. The latter is the result of disproportionate associations with BW and PW, usually larger with PW. PMID- 27180271 TI - First-trimester ultrasound determination of chorionicity in twin gestations using the lambda sign: a systematic review and meta-analysis. AB - OBJECTIVE: To evaluate the accuracy of first-trimester sonographic determination of chorionicity in twin gestations using the lambda sign. STUDY DESIGN: Electronic databases (MEDLINE, PROSPERO, Scopus, ClinicalTrials.gov, EMBASE, Sciencedirect) were searched from their inception until April 2016. We included only study assessing the accuracy lambda sign in prediction of monochorionicity in the first trimester. Forest plots for pooled sensitivity and specificity with 95% confidence intervals (CI) were generated. In addition, symmetric summary receiver-operating characteristic curves were plotted. The area under the curve (AUC) was also computed to evaluate the overall accuracy of the diagnostic test. RESULTS: Nine studies, including 2292 twins, were analysed. In all of these studies, identification of the lambda sign was used to diagnose chorionicity on real-time B-mode imaging. Twins were classified as monochorionic if there was a single placental mass in the absence of the lambda sign, and dichorionic if there was a single placental mass but the lambda sign was present or the placentas were not adjacent to each other. In all nine studies, placental histology or discordant fetal sex were used to confirm chorionicity. Pooled results from the meta-analysis showed that sensitivity of the presence of the lambda sign in the prediction of dichorionicity was 99% (95% CI 98-100%), and specificity was 95% (95% CI 92-97%). Pooled sensitivity of the absence of the lambda sign in the prediction of monochorionicity was 96% (95% CI 92-98%) and pooled specificity was 99% (95% CI 98-99%). The AUC for diagnostic accuracy was 0.99, and suggested very high diagnostic accuracy. CONCLUSION: The lambda sign predicts chorionicity with a high degree of accuracy before 14 weeks of gestation. Presence of the lambda sign indicates dichorionicity, and absence of the lambda sign indicates monochorionicity. All hospitals should encourage departments providing ultrasound services to determine chorionicity when examining women with twin pregnancies in the first trimester. As determination of chorionicity is most accurate before 14 weeks when the amnion and chorion have not yet fused, the first-trimester scan in twin pregnancy is paramount. PMID- 27180272 TI - Using the Female Sexual Function Index (FSFI) to evaluate sexual function in women with genital mutilation undergoing surgical reconstruction: a pilot prospective study. AB - OBJECTIVES: Few prospective studies have evaluated sexual function in women with female genital mutilation by cutting (FGM/C) before and after clitoral reconstructive surgery, and none used a validated questionnaire. A validated questionnaire, the Female Sexual Function Index (FSFI) was used for the first time, to assess the impact of reconstructive surgery on sexual function in women with female genital mutilation/cutting (FGM/C) before and after clitoral reconstructive surgery. STUDY DESIGN: Women with FGM/C consulting at the Nantes University Hospital for clitoral reconstruction between 2013 and 2014 were prospectively included. All patients completed a questionnaire at inclusion, describing their social, demographic, and FGM/C characteristics. They were also asked to complete the FSFI as well as a questionnaire about clitoral sensations, symptoms of depression or anxiety, and self-esteem before and 3 and 6 months after the surgery. Paired Wilcoxon and McNemar tests were used to compare data. RESULTS: Of the 12 women included, 9 (75%) had type II mutilations. Results showed a global sexual dysfunction (median FSFI summary score=17) before surgery. Clitoral sensations were absent in 8 women (67%). Six months after surgery, all FSFI dimensions except lubrication had improved significantly (median FSFI summary score=29, P=0.009). Ten women had clitoral sensations, and 11 (92%) were satisfied with their surgery. CONCLUSION: This study shows that 6 months after clitoral reconstructive surgery, women reported a multidimensional positive improvement in their sexual function. The FSFI is a promising tool for routine standardized assessment of the sexual function of women with FGM/C for determining appropriate management and assessing it. Larger studies with validated questionnaires assessing self-esteem, depression, and body image are also needed to develop an integrative approach and to provide evidence-based recommendations about management of these women. PMID- 27180273 TI - Cephalad-caudad versus transverse blunt expansion of the low transverse uterine incision during cesarean delivery. AB - It is imperative to have evidence-based guidelines for cesarean delivery. The aim of this meta-analysis was to evaluate the effectiveness of a cephalad-caudad compared to transverse blunt expansion of the uterine incision to reduce blood loss in women who underwent low-segment transverse cesarean delivery. We therefore performed a systematic search in electronic databases from their inception until March 2016. We included all randomized trials comparing cephalad caudad versus transverse (control group) blunt expansion of the uterine incision in women who underwent a low transverse cesarean delivery. The primary outcome was postpartum blood loss, defined as the mean amount of blood loss (mL). Two trials (921 women) were analyzed. After the transverse uterine incision in the lower uterine segment with the scalpel, the uterine incision was then bluntly expanded by the designated method. Blunt expansion of the primary incision was derived by placing the index fingers of the operating surgeon into the incision and pulling the fingers apart laterally (transverse group) or cephalad (cephalad caudad group). Women who were randomized in the cephalad-caudad group had lower: mean of postpartum blood loss, hemoglobin drop and hematocrit drop 24h after cesarean, unintended extension, uterine vessels injury, blood loss >1500mL and need for additional stitches. There was no statistically significant difference in the incidence of blood loss >1000mL, in the operating time and in post operative pain. In conclusion, expansion of the uterine incision with fingers in a cephalad-caudad direction is associated with better maternal outcomes and, therefore, should be preferred to transverse expansion during a cesarean delivery. PMID- 27180274 TI - [Therapeutic education programme for patients with chronic endocrine conditions: Transition from paediatric to adult services]. AB - The purpose of this study is to contribute to better identifying the transition of patients with chronic endocrine conditions from paediatric to adult department. The aim was to specify the means and the competences that must be used by patients and health care teams and which could be help to the best quality care. METHOD: We propose group sessions and individual interviews. A thematic analysis of the sessions and the responses to questionnaires have enabled the development of individual educational diagnosis and assess the autonomy of young adolescents. RESULTS: Fifty of 214 patients from paediatric services participated to therapeutic education program (TEP) in the last four years. This program is based on the psychic movements of adolescence. One year after the therapeutic education program session, 48 patients came to all the medical consultations and we observed a greater autonomy in adolescent patients. CONCLUSION: However, we must improve the modalities for including patients in this "transition program". PMID- 27180277 TI - Multiple arterial grafting for coronary revascularization: "A guide for the perplexed". AB - The surgical literature abounds with articles extolling the benefits of arterial grafting for patients with advanced coronary artery disease in need of surgical revascularization. However, examination of clinical performance demonstrates that extensive use of arterial grafting is highly selective and generally uncommon. Rather than to merely repeat multiple excellent recent literature reviews, the goal herein is to provide the reader with a guide to the evaluation of the current literature as well as to suggest fruitful areas for further research. More circumspect understanding of the strengths and weaknesses of our current knowledge base will not only help to explain the current apparent disparity between theory and practice but will hopefully inform future decision-making and patient care. PMID- 27180278 TI - SERAH: Supporting Expanded Roles for safe Abortion care by Health workers-A working group to enable the implementation of the WHO guidelines for expanded roles of health workers in safe abortion and postabortion care. PMID- 27180280 TI - Increasing maternal deaths due to obstetric hemorrhage in a setting of high HIV seroprevalence. PMID- 27180279 TI - Profile of pregnant women using delivery hut services of the Ballabgarh Health and Demographic Surveillance System in rural north India. AB - OBJECTIVE: To describe women who attended two delivery huts in rural Haryana, India. METHODS: The present observational study assessed routinely collected service provision data from two delivery huts located at primary health centers in the district of Faridabad. Data on sociodemographic characteristics, prenatal care, use of free transport services, and maternal and neonatal indicators at delivery were assessed for all pregnant women who used the delivery hut services from January 2012 to June 2014. RESULTS: During the study period, 1796 deliveries occurred at the delivery huts. The mean age of the mothers was 23.3 +/- 3.3 years (95% confidence interval 23.1-23.5). Of 1648 mothers for whom data were available, 1039 (63.0%) had travelled less than 5 km to the delivery hut. The proportion of mothers who belonged to a lower caste increased from 31.0% (193/622) in 2012 to 41.1% (162/394) in 2014. The proportion of mothers who were illiterate also increased, from 8.1% (53/651) in 2012 to 26.4% (104/394) in 2014. CONCLUSION: Belonging to a disadvantaged social group (in terms of caste or education) was not an obstacle to use of delivery hut services. The delivery huts might have satisfied some unmet needs of community members in rural India. PMID- 27180276 TI - Roles of extracellular nucleotides and P2 receptors in ectodomain shedding. AB - Ectodomain shedding of integral membrane receptors results in the release of soluble molecules and modification of the transmembrane portions to mediate or modulate extracellular and intracellular signalling. Ectodomain shedding is stimulated by a variety of mechanisms, including the activation of P2 receptors by extracellular nucleotides. This review describes in detail the roles of extracellular nucleotides and P2 receptors in the shedding of various cell surface molecules, including amyloid precursor protein, CD23, CD62L, and members of the epidermal growth factor, immunoglobulin and tumour necrosis factor families. This review discusses the mechanisms involved in P2 receptor-mediated shedding, demonstrating central roles for the P2 receptors, P2X7 and P2Y2, and the sheddases, ADAM10 and ADAM17, in this process in a number of cell types. PMID- 27180281 TI - Xanthomonas citri subsp. citri surface proteome by 2D-DIGE: Ferric enterobactin receptor and other outer membrane proteins potentially involved in citric host interaction. AB - : Xanthomonas citri subsp. citri (XAC) is the causative agent of citrus canker, a disease of great economic impact around the world. Understanding the role of proteins on XAC cellular surface can provide new insights on pathogen-plant interaction. Surface proteome was performed in XAC grown in vivo (infectious) and in vitro (non-infectious) conditions, by labeling intact cells followed by cellular lysis and direct 2D-DIGE analysis. Seventy-nine differential spots were analyzed by mass spectrometry. Highest relative abundance for in vivo condition was observed for spots containing DnaK protein, 60kDa chaperonin, conserved hypothetical proteins, malate dehydrogenase, phosphomannose isomerase, and ferric enterobactin receptors. Elongation factor Tu, OmpA-related proteins, Oar proteins and some Ton-B dependent receptors were found in spots decreased in vivo. Some proteins identified on XAC's surface in infectious condition and predicted to be cytoplasmic, such as DnaK and 60KDa chaperonin, have also been previously found at cellular surface in other microorganisms. This is the first study on XAC surface proteome and results point to mediation of molecular chaperones in XAC citrus interaction. The approach utilized here can be applied to other pathogen host interaction systems and help to achieve new insights in bacterial pathogenicity toward promising targets of biotechnological interest. BIOLOGICAL SIGNIFICANCE: This research provides new insights for current knowledge of the Xanthomonas sp. pathogenicity. For the first time the 2D-DIGE approach was applied on intact cells to find surface proteins involved in the pathogen-plant interaction. Results point to the involvement of new surface/outer membrane proteins in the interaction between XAC and its citrus host and can provide potential targets of biotechnological interest for citrus canker control. PMID- 27180275 TI - Transition from inflammation to proliferation: a critical step during wound healing. AB - The ability to rapidly restore the integrity of a broken skin barrier is critical and is the ultimate goal of therapies for hard-to-heal-ulcers. Unfortunately effective treatments to enhance healing and reduce scarring are still lacking. A deeper understanding of the physiology of normal repair and of the pathology of delayed healing is a prerequisite for the development of more effective therapeutic interventions. Transition from the inflammatory to the proliferative phase is a key step during healing and accumulating evidence associates a compromised transition with wound healing disorders. Thus, targeting factors that impact this phase transition may offer a rationale for therapeutic development. This review summarizes mechanisms regulating the inflammation-proliferation transition at cellular and molecular levels. We propose that identification of such mechanisms will reveal promising targets for development of more effective therapies. PMID- 27180282 TI - Comprehensive quantification of N-glycoproteome in Fusarium graminearum reveals intensive glycosylation changes against fungicide. AB - Glycoproteomics is greatly developed in recent years and big data of N glycoproteome in mammalian tissues and cells were already established. However, the glycoproteomic studies on plant, fungus and bacteria are far left behind. In this study, we comprehensively mapped and quantified the N-glycosylation of Fusarium graminearum by combining stable isotope dimethyl labeling, hydrophilic interaction chromatography (HILIC) and high-resolution mass spectrometry. The N glycosylation changes in Fusarium graminearum after fungicide treatment were extensively studied. Altogether we identified 927 N-glycopeptides, corresponding to 406 proteins and 774 sites and the glycosylation level was found to be largely down-regulated upon fungicide treatment. With the help of advanced bioinformatics, it was found that the N-glycoproteome changes were highly enriched in cell wall, membrane and extracellular regions. Moreover, the fungal metabolism, protein and glycosylation synthesis, and protease and glycosyl transferase activity were all closely related with the down-regulated proteins, indicates that fungicide may affect fungal development in these aspects. These results will be useful for future studies on fungal biology. The established system for N-glycoproteome quantification has comparative or better performance compared with previous strategies and will be helpful in N-glycoproteomics of fungus and other species. SIGNIFICANCE: We developed a robust HILIC-based system for N-glycoproteome quantification in fungus and established the largest quantitative N-glycosylation dataset in fungus, showing the high performance of the new system. The identified N-glycoproteins were proved to be high confident due to the high percentage of proteins in extracellular region and plasma. The quantification results were also accuracy and reproducible in two replicates. By the help of advanced bioinformatic tools, the obtained data was systematically analyzed. It was found that the N-glycosylation level was largely changed in cell wall, membrane and extracellular regions. Moreover, the cell metabolism, protein synthesis, and protease activity were also greatly deceased after fungicide treatment. PMID- 27180283 TI - Quantitative interactome reveals that porcine reproductive and respiratory syndrome virus nonstructural protein 2 forms a complex with viral nucleocapsid protein and cellular vimentin. AB - Porcine reproductive and respiratory syndrome virus (PRRSV) is an Arterivirus that has heavily impacted the global swine industry. The PRRSV nonstructural protein 2 (nsp2) plays crucial roles in viral replication and host immune regulation, most likely by interacting with viral or cellular proteins that have not yet been identified. In this study, a quantitative interactome approach based on immunoprecipitation and stable isotope labeling with amino acids in cell culture (SILAC) was performed to identify nsp2-interacting proteins in PRRSV infected cells with an nsp2-specific monoclonal antibody. Nine viral proteins and 62 cellular proteins were identified as potential nsp2-interacting partners. Our data demonstrate that the PRRSV nsp1alpha, nsp1beta, and nucleocapsid proteins all interact directly with nsp2. Nsp2-interacting cellular proteins were classified into different functional groups and an interactome network of nsp2 was generated. Interestingly, cellular vimentin, a known receptor for PRRSV, forms a complex with nsp2 by using viral nucleocapsid protein as an intermediate. Taken together, the nsp2 interactome under the condition of virus infection clarifies a role of nsp2 in PRRSV replication and immune evasion. BIOLOGICAL SIGNIFICANCE: Viral proteins must interact with other virus-encoded proteins and/or host cellular proteins to function, and interactome analysis is an ideal approach for identifying such interacting proteins. In this study, we used the quantitative interactome methodology to identify the viral and cellular proteins that potentially interact with the nonstructural protein 2 (nsp2) of porcine reproductive and respiratory syndrome virus (PRRSV) under virus infection conditions, thus providing a rich source of potential viral and cellular interaction partners for PRRSV nsp2. Based on the interactome data, we further demonstrated that PRRSV nsp2 and nucleocapsid protein together with cellular vimentin, form a complex that may be essential for viral attachment and replication, which partly explains the role of nsp2 in PRRSV replication and immune evasion. PMID- 27180284 TI - Insights into the mechanisms and the emergence of sex-differences in pain. AB - Recent studies describe sex and gender as critical factors conditioning the experience of pain and the strategies to respond to it. It is now clear that men and women have different physiological and behavioral responses to pain. Some pathological pain states are also highly sex-specific. This clinical observation has been often verified with animal studies which helped to decipher the mechanisms underlying the observed female hyper-reactivity and hyper-sensitivity to pain states. The role of gonadal hormones in the modulation of pain responses has been a straightforward hypothesis but, if pertinent in many cases, cannot fully account for this complex sensation, which includes an important cognitive component. Clinical and fundamental data are reviewed here with a special emphasis on possible developmental processes giving rise to sex-differences in pain processing. PMID- 27180286 TI - Intentions and willingness to drive while drowsy among university students: An application of an extended theory of planned behavior model. AB - A web-based questionnaire was used to assess the utility of constructs from the Theory of Planned Behavior (TPB) and the Prototype Willingness Model (PWM) to predict intentions and willingness to engage in drowsy driving in a sample of 450 university students. Those students who reported more favorable attitudes and subjective norm and greater perceived control and willingness in relation to drowsy driving behavior were more likely to report stronger intentions to engage in drowsy driving behavior. Augmenting the TPB constructs with the PWM construct of willingness significantly explained up to an additional 8 percent of the variance in drowsy driving intention. Perceived behavioral control and willingness were consistently the strongest predictors of drowsy driving intention in the augmented model, which together with the control (personal) variables explained up to 70 percent of the variance in intention. Thus, the Theory of Planned Behavior and the Prototype Willingness Model may be useful for understanding motivational influences on drowsy driving behavior in young people and present promising theoretical frameworks for designing more effective interventions against drowsy driving in this population. PMID- 27180287 TI - Multi-mode reliability-based design of horizontal curves. AB - Recently, reliability analysis has been advocated as an effective approach to account for uncertainty in the geometric design process and to evaluate the risk associated with a particular design. In this approach, a risk measure (e.g. probability of noncompliance) is calculated to represent the probability that a specific design would not meet standard requirements. The majority of previous applications of reliability analysis in geometric design focused on evaluating the probability of noncompliance for only one mode of noncompliance such as insufficient sight distance. However, in many design situations, more than one mode of noncompliance may be present (e.g. insufficient sight distance and vehicle skidding at horizontal curves). In these situations, utilizing a multi mode reliability approach that considers more than one failure (noncompliance) mode is required. The main objective of this paper is to demonstrate the application of multi-mode (system) reliability analysis to the design of horizontal curves. The process is demonstrated by a case study of Sea-to-Sky Highway located between Vancouver and Whistler, in southern British Columbia, Canada. Two noncompliance modes were considered: insufficient sight distance and vehicle skidding. The results show the importance of accounting for several noncompliance modes in the reliability model. The system reliability concept could be used in future studies to calibrate the design of various design elements in order to achieve consistent safety levels based on all possible modes of noncompliance. PMID- 27180285 TI - Simvastatin inhibits protein isoprenylation in the brain. AB - Evidence suggests that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, may reduce the risk of Alzheimer's disease (AD). Statin action in patients with AD, as in those with heart disease, is likely to be at least partly independent of the effects of statins on cholesterol. Statins can alter cellular signaling and protein trafficking through inhibition of isoprenylation of Rho, Cdc42, and Rab family GTPases. The effects of statins on protein isoprenylation in vivo, particularly in the central nervous system, are poorly studied. We utilized two-dimensional gel electrophoresis approaches to directly monitor the levels of isoprenylated and non-isoprenylated forms of Rho and Rab family GTPases. We report that simvastatin significantly inhibits RhoA and Rab4, and Rab6 isoprenylation at doses as low as 50nM in vitro. We also provide the first in vivo evidence that statins inhibit the isoprenylation of RhoA in the brains of rats and RhoA, Cdc42, and H-Ras in the brains of mice treated with clinically relevant doses of simvastatin. PMID- 27180288 TI - The timing of surgery for congenital cataracts: Minimizing the risk of glaucoma following cataract surgery while optimizing the visual outcome. PMID- 27180289 TI - The timing of surgery for congenital cataracts: Delayed surgery for best surgical outcomes. PMID- 27180290 TI - An epidemiological study of animals dermatomycoses in Iran. AB - OBJECTIVE: To determine the fungal species isolated from skin lesions of different animals suspected of having dermatomycoses and their prevalence in different regions of Iran. MATERIALS AND METHODS: A total of 1011 animals (292 dogs, 229 cats, 168 horses, 100 camels, 98 cows, 60 squirrels, 37 birds, 15 sheep, 6 goats, 5 rabbits and 1 fox) suspected of having dermatomycoses were examined. The samples were obtained by plucking the hairs and feathers with forceps around the affected area and scraping the epidermal scales with a sterile scalpel blade. All collected samples were analyzed by direct microscopy and culture. Laboratory identification of the fungal isolates was based on their colonial, microscopic and biochemical characteristics. RESULTS: Fungal agents were recovered from 553 (54.7%) animals suspected of having dermatomycoses. Of 553 confirmed cases, 255 (49.7%) were positive for dermatophytosis, 251 (45.4%) for Malassezia dermatitis, 14 (2.5%) for candidiasis, 12 (2.2%) for aspergillosis and 1 (0.2%) for zygomycosis. Cats (36.3%) were the most prevalent infected animals, followed by camels (13.4%), dogs (12.8%), horses (12.5%), cows (12.3%), squirrels (5.4%), birds (3.6%), sheep (2%), goats (1.1%), rabbits (0.4%) and fox (0.2%). Microsporum canis (M. canis) was the most frequent fungus isolated from dogs and fox, Malassezia pachydermatis (M. pachydermatis) from cats, horses and squirrels, Trichophyton verrucosum (T. verrucosum) from cows and camels, T. mentagrophytes var. mentagrophytes from sheep, goats and rabbits, and Aspergillus fumigatus (A. fumigatus) from birds. CONCLUSION: The results suggested that periodic screening of animals suspected of having dermatomycoses and necessary treatments could help in the management of their public health problem. PMID- 27180292 TI - Optimization of microwave-assisted extraction of polysaccharide from Psidium guajava L. fruits. AB - This study deals with the optimization of microwave assisted extraction of polysaccharide from Psidium guajava L. fruit using Response surface methodology. To evaluate the effect of three independent variables, Water to plant material ratio, microwave power used for extraction and Irradiation time, central composite design has been employed. The yield is considered as dependent variable. The design model estimated the optimum yield of 6.81677% at 200W microwave power level, 3:1 water to plant material ratio and 20min of irradiation time. Three factors three levels Central composite design coupled with RSM was used to model the extraction process. ANOVA was performed to find the significance of the model. The polysaccharide extracted using microwave assisted extraction process was analyzed using FTIR Spectroscopy. PMID- 27180291 TI - Curcumin loaded chitosan nanoparticles impregnated into collagen-alginate scaffolds for diabetic wound healing. AB - Diabetic wounds are a common complication in patients with diabetes that often lead to amputation. Although the pathophysiology of diabetic wound is multifactorial, chronic inflammation and lack of tissue regeneration leads to impair wound healing in diabetes. Application of curcumin (CUR) which is a well known anti-inflammatory and antioxidant agent could be better strategy in diabetic wound healing. However, low bioavailability and poor stability of CUR hinders its application. Hence, in present study a novel nanohybrid scaffold has been prepared by incorporating CUR in chitosan nanoparticles (CSNPs) to improve stability and solubility followed by impregnation of prepared CUR-CSNPs into collagen scaffold (nanohybrid scaffold) for better tissue regeneration application. The prepared CUR-CSNPs were evaluated for particle size, zeta potential, SEM, differential scanning calorimetry and X-ray powder diffraction studies and the novel nanohybrid is evaluated for morphology, biodegradability, biocompatibility, in vitro drug release and in vivo wound healing studies. The results of NPs evaluation suggest the better stability and solubility of CUR. The nanohybrid scaffold showed good in vitro characteristics in terms of better water uptake, biocompatibility and sustained drug availability. The results of in vivo wound closure analysis revealed that nanohybrid scaffold treated wounds contracted significantly (p<0.001) faster than the wounds from the control and placebo scaffold groups. Further, the obtained results suggest that complete epithelialization with thick granulation tissue formation occur in nanohybrid scaffold group, whereas lack of compact collagen deposition in placebo scaffold group and presence of inflammatory cells in control group was observed. Hence, the present study suggests that the synergistic combination of CUR (anti inflammatory and anti-oxidant), chitosan (sustain drug carrier, wound healing) and collagen (established wound healer as scaffold) is a promising strategy to address various pathological manifestations of diabetic wounds and have better wound healing capability. PMID- 27180293 TI - Pure keratin membrane and fibers from chicken feather. AB - In this research, keratin was extracted from the disposable chicken feather using l-cysteine as reducing agent. Then, it was re-dissolved in the sodium carbonate sodium bicarbonate buffer, and the pure keratin membrane and fiber were fabricated by doctor-blade casting process and wet spinning method, respectively. Scanning electron microscopy (SEM), fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD) and thermogravimetric analysis (TGA) were used to characterize the chemical and physical properties of resulting powder, membrane and fiber. Compared with the raw chicken feather, the regenerated keratin materials retain its chemical structure and thermal stability, their relative crystallinity is a little different depend on the shaping method, which leads to the difference in moisture regain. The mechanical results show that tensile strength of the keratin membrane researches 3.5MPa, have potential application in biomedical fields. However, the keratin fiber presents low tenacity, i.e. 0.5cN/dtex, this problem should be solved in order to apply the new fiber in textile and material science. PMID- 27180294 TI - AkP from mushroom Termitomyces clypeatus is a proteoglycan specific protease with apoptotic effect on HepG2. AB - Termitomyces clypeatus is an edible mushroom, prized for its therapeutic values and as producer of industrially important enzymes. However, the biomedical efficacies of anticancer proteases have not been reported yet. The present study aimed to purify and characterize a serine protease (AkP) from T. clypeatus for investigating cytotoxic potency on HepG2, Hep3B, and compared the effect on normal hepatic L-02 cells. Purification and biochemical characterization of AkP were evaluated by three stage chromatography, 1D/2D-SDS-PAGE, 1D zymography, far UV CD spectral analysis, N-terminal sequencing, MALDI-TOF/MS-MS analysis and enzyme kinetics studies. AkP could cleave the growth promoting cell surface proteoglycans of HepG2, corroborated by RP-HPLC analysis. AkP (IC50: 75+/-1.18nM) mediated anti-proliferative activity solely on HepG2 cells through the induction of apoptosis. Augmentation of apoptosis was attributed to up-regulation of p53 and Bax protein expression succeeded by caspase-3 activation. Serine protease inhibitor phenyl methane sulfonyl fluoride (PMSF) inhibited both its proteolytic activity and cytotoxicity on HepG2. These findings demonstrate that AkP could be an effective biomolecule for killing of cancer cells by p53 restoration and surface proteoglycans cleavage. PMID- 27180295 TI - U(VI) biosorption by bi-functionalized Pseudomonas putida @ chitosan bead: Modeling and optimization using RSM. AB - In this work, Pseudomonas putida cells immobilized into chitosan beads (PICB) were synthesized to investigate the impact of microorganism entrapment on biosorption capacity of prepared biosorbent for U(VI) biosorption from aqueous solutions. Response Surface Methodology (RSM) based on Central Composite Design (CCD) was utilized to evaluate the performance of the PICB in comparison with chitosan beads (CB) under batch mode. Performing experiments under optimal condition sets viz. pH 5, initial U(VI) concentration 500mg/L, biosorbent dosage 0.4g/L and 20wt.% bacterial cells showed that the observed biosorption capacity enhanced by 1.27 times from 398mg/g (CB) to 504mg/g (PICB) that confirmed the effectiveness of cells immobilization process. FTIR and potentiometric titration were then utilized to characterize the prepared biosorbents. While the dominant functional group in the binding process was NH3(+) (4.78meq/g) in the CB, the functional groups of NH3(+), NH2, OH, COOH (6.00meq/g) were responsible for the PICB. The equilibrium and kinetic studies revealed that the Langmuir isotherm model and the pseudo-second-order kinetic model were in better fitness with the CB and PICB experimental data. In conclusion, the present study indicated that the PICB could be a suitable biosorbent for uranium (VI) biosorption from aqueous solutions. PMID- 27180296 TI - Unravelling the potential of a new uracil phosphoribosyltransferase (UPRT) from Arabidopsis thaliana in sensitizing HeLa cells towards 5-fluorouracil. AB - In silico studies with uracil phosphoribosyltransferase from Arabidopsis thaliana (AtUPRT) revealed its lower binding energies for uracil and 5-fluorouracil (5-FU) as compared to those of bacterial UPRT indicating the prospective of AtUPRT in gene therapy implications. Hence, AtUPRT was cloned and stably expressed in cervical cancer cells (HeLa) to investigate the effect of prodrug 5-FU on these transfected cancer cells. The treatment of AtUPRT-expressing HeLa (HeLa-UPP) cells with 5-FU for 72h resulted in significant decrease in cell viability. Moreover, 5-FU was observed to induce apoptosis and perturb mitochondrial membrane potential in HeLa-UPP cells. While cell cycle analysis revealed significant S-phase arrest as a result of 5-FU treatment in HeLa-UPP cells, quantitative gene expression analysis demonstrated simultaneous upregulation of important cell cycle related genes, cyclin D1 and p21. The survival fractions of non-transfected, vector-transfected and AtUPRT-transfected HeLa cells, following 5-FU treatment, were calculated to be 0.425, 0.366 and 0.227, respectively. PMID- 27180297 TI - Characterization of banana starches obtained from cultivars grown in Brazil. AB - The starch market is constantly evolving and studies that provide information about the physical and rheological properties of native starches to meet the diverse demands of the sector are increasingly necessary. In this study starches obtained from five cultivars of banana were analyzed for size and shape of granules, crystallinity, chemical composition, resistant starch, swelling power, solubility, thermal and paste properties. The granules of starch were large (36.58-47.24MUm), oval, showed crystallinity pattern type B and the index of crystallinity ranged from 31.94 to 34.06%. The phosphorus content ranged from 0.003 to 0.011%, the amylose ranged from 25.13 to 29.01% and the resistant starch ranged from 65.70 to 80.28%. The starches showed high peak viscosity and breakdown, especially those obtained from 'Nanicao' and 'Grand Naine'. Peak temperature of gelatinization was around 71 degrees C, the enthalpy change (DeltaH) ranged from 9.45 to 14.73Jg(-1). The starch from 'Grand Naine' showed higher swelling power (15.19gg(-1)) and the starch from 'Prata-Ana' higher solubility (11.61%). The starches studied are highlighted by their physical and chemical characteristics and may be used in several applications. PMID- 27180298 TI - Characterisation of molten globule-like state of sheep serum albumin at physiological pH. AB - Sheep serum albumin (SSA) is a 583 amino acid residues long multidomain monomeric protein which is rich in cysteine and low in tryptophan content. The serum albumins (from human, bovine and sheep) play a vital role among all proteins investigated until now, as they are the most copious circulatory proteins. We have purified SSA from sheep kidneys by a simple and efficient two-step purification procedure. Further, we have studied urea-induced denaturation of SSA by monitoring changes in the difference absorption coefficient at 287nm (Deltaepsilon287), intrinsic fluorescence emission intensity at 347nm (F347) and mean residue ellipticity at 222nm ([theta]222) at pH 7.4 and 25 degrees C. The coincidence of denaturation curves of these optical properties suggests that urea induced denaturation is a bi-phasic process (native (N) state<->intermediate (X) state<->denatured (D) state) with a stable intermediate populated around 4.2-4.7M urea. The intermediate (X) state was further characterized by the far-UV and near UV CD, dynamic light scattering (DLS) and fluorescence using 1-anilinonaphthalene 8-sulfonic acid (ANS) binding method. All denaturation curves were analyzed for Gibbs free energy changes associated with the equilibria, N state<->X state and X state<->D state in the absence of urea. PMID- 27180300 TI - Cloning, expression and characterization of a mucin-binding GAPDH from Lactobacillus acidophilus. AB - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a ubiquitous enzyme involved in glycolysis. It is also referred to as a moonlighting protein as it has many diverse functions like regulation of apoptosis, iron homeostasis, cell-matrix interactions, adherence to human colon etc. apart from its principal role in glycolysis. Lactobacilli are lactic acid bacteria which colonize the human gut and confer various health benefits to humans. In the present study, we have cloned, expressed and purified the GAPDH from Lactobacillus acidophilus to get a recombinant product (r-LaGAPDH) and characterized it. Size exclusion chromatography shows that r-LaGAPDH exists as a tetramer in solution and have a mucin binding and hemagglutination activity indicating carbohydrate like binding adhesion mechanism. Fluorescence spectroscopy studies showed an interaction of r LaGAPDH with mannose, galactose, N-acetylgalactosamine and N-acetylglucosamine with a Kd of 3.6+/-0.7*10(-3)M, 4.34+/-0.09*10(-3)M, 4+/-0.87*10(-3)M and 3.7+/ 0.28*10(-3)M respectively. We hope that this preliminary data will generate more interest in further elucidation of the roles of GAPDH in the adhesion processes of the bacteria. PMID- 27180299 TI - Keratin made micro-tubes: The paradoxical thermal behavior of cortex and cuticle. AB - Keratin micro-tubes were obtained by heating medullated keratin fibres to temperatures above 230 degrees C under nitrogen atmosphere, when, as documented by microscopy, the cortex (the core of the fibre) melts from the medulla outwards, followed by pyrolysis of the material through the remaining solid cuticle (shell) layer. The resulted hollow tubes from fibres void of cortical material keep the external cuticle structure, as shown by AFM investigation, and the moisture sorption properties of the initial keratin fibre. Despite similar amino-acid compositions of cuticle and cortex the two morphological components differ significantly in their thermal behaviour, which appears to be a "cortex cuticle thermal stability paradox". PMID- 27180301 TI - Preclinical assessment of the endothelial shear stress in porcine-based models following implantation of two different bioresorbable scaffolds: effect of scaffold design on the local haemodynamic micro-environment. PMID- 27180302 TI - Novel PARADIGM in carotid revascularisation: Prospective evaluation of All-comer peRcutaneous cArotiD revascularisation in symptomatic and Increased-risk asymptomatic carotid artery stenosis using CGuardTM MicroNet-covered embolic prevention stent system. AB - AIMS: Our aim was to determine (1) periprocedural and 30-day clinical safety and efficacy of the CGuard MicroNet-covered embolic prevention carotid stent system (MN-EPS) in routine use for unselected carotid stenosis (CS) patients undergoing CAS, as well as (2) feasibility of MN-EPS post-dilatation optimisation to minimise residual stenosis after CAS. METHODS AND RESULTS: This was a non industry-funded, prospective academic study in all-referrals-tracked symptomatic and asymptomatic CS. In asymptomatic lesions, intervention was mandated only in case of increased stroke risk CS features. There was independent neurologist evaluation before CAS, at 48 hours and 30 days. There was external source data verification, angiographic core lab, and statistical analysis. Over 11 months, 108 referrals were recommended by the NeuroVascular Team for revascularisation: 101 (51-86 years, 55 symptomatic, evolving stroke in nine) underwent 106 (100% MN EPS use) neuroprotection device-assisted (46% proximal, 54% distal) CAS; CEA was performed in seven. MN-EPS device success was 99.1%. Angiographic diameter stenosis was reduced from 83+/-9% to 6.7+/-5% (p<0.001). No MN-EPS foreshortening/elongation occurred (30 mm long was 29.82+/-0.68 mm; 40 mm long was 39.89+/-0.59 mm). The periprocedural death/major stroke/MI rate was 0%. One event, with no change in NIHSS or modified Rankin Scale and no clinical sequel, was adjudicated by the clinical events committee as minor stroke (0.9%). By 30 days there were no new events (0%). CONCLUSIONS: These increased risk consecutive patient data (1) indicate safety and efficacy of routine MN-EPS use in achieving endovascular reconstruction across all-comer CS lesion subsets, and (2) are consistent with MN-EPS protection against cerebral events extending throughout the stent healing period. PMID- 27180303 TI - Impact of stent size on angiographic and clinical outcomes after implantation of everolimus-eluting bioresorbable scaffolds in daily practice: insights from the ISAR-ABSORB registry. AB - AIMS: We sought to evaluate the impact of stent size on angiographic and clinical outcomes after implantation of everolimus-eluting bioresorbable stents (BRS) in routine clinical practice. METHODS AND RESULTS: All consecutive patients undergoing BRS implantation at two centres in Munich, Germany, were included prospectively. The patient population was divided according to the diameter of the implanted BRS. Angiographic surveillance was scheduled at six to eight months after stent implantation and films were analysed in a core laboratory. A BRS with 2.5 mm diameter was implanted in 101 patients and BRS >2.5 mm diameter in 318. Baseline patient characteristics were similar in both groups. Reference vessel diameter was 2.36+/-0.22 mm in patients with an implanted 2.5 mm BRS and 3.03+/ 0.40 mm in the other group (p<0.001). At angiographic follow-up, in-stent late luminal loss (0.28+/-0.47 mm vs. 0.25+/-0.52 mm, p=0.74) was similar in both groups, though binary angiographic restenosis was numerically higher in patients treated with a 2.5 mm BRS (12.5% vs. 6.1%, p=0.05). After 12 months, the rate of the composite of death, myocardial infarction or target lesion revascularisation was 15.7% vs. 12.3% (p=0.49). Definite stent thrombosis was detected in 1.0% vs. 3.1% (p=0.31). CONCLUSIONS: In patients treated with BRS in routine clinical practice, angiographic and clinical outcomes were comparable in patients treated with a 2.5 mm stent as compared with those treated with a larger stent size. PMID- 27180304 TI - The CLEAR-ROAD study: evaluation of a new dual layer micromesh stent system for the carotid artery. AB - AIMS: The aim of this study was to evaluate the 30-day clinical outcome of treatment using the Roadsaver carotid stent in non-consecutive subjects at high risk for carotid endarterectomy requiring revascularisation. METHODS AND RESULTS: The CLEAR-ROAD study is a prospective, multinational, single-arm, physician initiated study planned to include 100 patients in nine centres in Belgium, Italy and Germany. The primary endpoint was the 30-day rate of major adverse events (MAE), defined as the cumulative incidence of any death, stroke or myocardial infarction (MI). The use of embolic protection devices (EPDs) was not mandatory; 31.0% of the patients were symptomatic and in 58.0% of the patients EPDs were used. Technical success was achieved in all cases. The 30-day MAE rate was 2.1% (one patient experienced MI followed by death; another patient experienced a stroke within the first 30 days after procedure). While no statistical analysis could be performed, subgroup data suggested that there were no notable differences in the 30-day MAE rate between symptomatic and asymptomatic patients, or between EPD use. CONCLUSIONS: The 30-day clinical outcome of 100 patients treated with a dual layer micromesh carotid stent (Roadsaver) shows promising results. The Roadsaver stent is a safe and effective device for endovascular treatment of subjects at high risk for carotid endarterectomy. PMID- 27180305 TI - Activation of endogenous TRPV1 fails to induce overstimulation-based cytotoxicity in breast and prostate cancer cells but not in pain-sensing neurons. AB - Vanilloids including capsaicin and resiniferatoxin are potent transient receptor potential vanilloid type 1 (TRPV1) agonists. TRPV1 overstimulation selectively ablates capsaicin-sensitive sensory neurons in animal models in vivo. The cytotoxic mechanisms are based on strong Na(+) and Ca(2+) influx via TRPV1 channels, which leads to mitochondrial Ca(2+) accumulation and necrotic cell swelling. Increased TRPV1 expression levels are also observed in breast and prostate cancer and derived cell lines. Here, we examined whether potent agonist induced overstimulation mediated by TRPV1 might represent a means for the eradication of prostate carcinoma (PC-3, Du 145, LNCaP) and breast cancer (MCF7, MDA-MB-231, BT-474) cells in vitro. While rat sensory neurons were highly vanilloid-sensitive, normal rat prostate epithelial cells were resistant in vivo. We found TRPV1 to be expressed in all cancer cell lines at mRNA and protein levels, yet protein expression levels were significantly lower compared to sensory neurons. Treatment of all human carcinoma cell lines with capsaicin didn't lead to overstimulation cytotoxicity in vitro. We assume that the low vanilloid-sensitivity of prostate and breast cancer cells is associated with low expression levels of TRPV1, since ectopic TRPV1 expression rendered them susceptible to the cytotoxic effect of vanilloids evidenced by plateau-type Ca(2+) signals, mitochondrial Ca(2+) accumulation and Na(+)- and Ca(2+)-dependent membrane disorganization. Moreover, long-term monitoring revealed that merely the ectopic expression of TRPV1 stopped cell proliferation and often induced apoptotic processes via strong activation of caspase-3 activity. Our results indicate that specific targeting of TRPV1 function remains a putative strategy for cancer treatment. PMID- 27180307 TI - Repositioning of drugs for intervention in tumor progression and metastasis: Old drugs for new targets. AB - The increasing unraveling of the molecular basis of cancer offers manifold novel options for intervention strategies. However, the discovery and development of new drugs for potential clinical applications is a tremendously time-consuming and costly process. Translating a novel lead candidate compound into an approved clinical drug takes often more than a decade, and the success rate is very low due to versatile efforts including defining its pharmacokinetics, pharmacodynamics, side effects as well as lack of sufficient efficacy. Thus, strategies are needed to minimize time and costs, while maximizing success rates. A very attractive strategy for novel cancer therapeutic options is the repositioning of already approved drugs. These medicines, approved for the treatment of non-malignant disorders, have already passed some early costs and time, have been tested in humans and are ready for clinical trials as anti-cancer drugs. Here we discuss the repositioning of nonsteroidal anti-inflammatory drugs (NSAID), statins, anti-psychotic drugs, anti-helminthic drugs and vitamin D as anti-tumor agents. We focus on their novel actions and potential for inhibition of cancer growth and metastasis by interfering with target molecules and pathways, which drive these malignant processes. Furthermore, important pre clinical and clinical data are reviewed herein, which elucidate their therapeutic mechanisms which enable their repositioning for cancer therapy and disruption of metastasis. PMID- 27180306 TI - ABC transporters as mediators of drug resistance and contributors to cancer cell biology. AB - The extrusion of anticancer drugs by members of the ATP-binding cassette (ABC) transporter family is one of the most widely recognized mechanisms of multidrug resistance, and can be considered a hijacking of their normal roles in the transport of xenobiotics, metabolites and signaling molecules across cell membranes. While roles in cancer multidrug resistance have been clearly demonstrated for P-glycoprotein (P-gp), Breast Cancer Resistance Protein (BCRP) and Multidrug Resistance Protein 1 (MRP1), direct evidence for a role in multidrug resistance in vivo is lacking for other family members. A less well understood but emerging theme is the drug efflux-independent contributions of ABC transporters to cancer biology, supported by a growing body of evidence that their loss or inhibition impacts on the malignant potential of cancer cells in vitro and in vivo. As with multidrug resistance, these contributions likely represent a hijacking of normal ABC transporter functions in the efflux of endogenous metabolites and signaling molecules, however they may expand the clinical relevance of ABC transporters beyond P-gp, BCRP and MRP1. This review summarizes established and emerging roles for ABC transporters in cancer, with a focus on neuroblastoma and ovarian cancer, and considers approaches to validate and better understand these roles. PMID- 27180308 TI - Long non-coding RNAs: An emerging powerhouse in the battle between life and death of tumor cells. AB - Long non-coding RNAs (lncRNAs) represent a class of non-protein coding transcripts longer than 200 nucleotides that have aptitude for regulating gene expression at the transcriptional, post-transcriptional or epigenetic levels. In recent years, lncRNAs, which are believed to be the largest transcript class in the transcriptomes, have emerged as important players in a variety of biological processes. Notably, the identification and characterization of numerous lncRNAs in the past decade has revealed a role for these molecules in the regulation of cancer cell survival and death. It is likely that this class of non-coding RNA constitutes a critical contributor to the assorted known or/and unknown mechanisms of intrinsic or acquired drug resistance. Moreover, the expression of lncRNAs is altered in various patho-physiological conditions, including cancer. Therefore, lncRNAs represent potentially important targets in predicting or altering the sensitivity or resistance of cancer cells to various therapies. Here, we provide an overview on the molecular functions of lncRNAs, and discuss their impact and importance in cancer development, progression, and therapeutic outcome. We also provide a perspective on how lncRNAs may alter the efficacy of cancer therapy and the promise of lncRNAs as novel therapeutic targets for overcoming chemoresistance. A better understanding of the functional roles of lncRNA in cancer can ultimately translate to the development of novel, lncRNA based intervention strategies for the treatment or prevention of drug-resistant cancer. PMID- 27180309 TI - Mechanisms and consequences of bacterial resistance to antimicrobial peptides. AB - Cationic antimicrobial peptides (AMPs) are an intrinsic part of the human innate immune system. Over 100 different human AMPs are known to exhibit broad-spectrum antibacterial activity. Because of the increased frequency of resistance to conventional antibiotics there is an interest in developing AMPs as an alternative antibacterial therapy. Several cationic peptides that are derivatives of AMPs from the human innate immune system are currently in clinical development. There are also ongoing clinical studies aimed at modulating the expression of AMPs to boost the human innate immune response. In this review we discuss the potential problems associated with these therapeutic approaches. There is considerable experimental data describing mechanisms by which bacteria can develop resistance to AMPs. As for any type of drug resistance, the rate by which AMP resistance would emerge and spread in a population of bacteria in a natural setting will be determined by a complex interplay of several different factors, including the mutation supply rate, the fitness of the resistant mutant at different AMP concentrations, and the strength of the selective pressure. Several studies have already shown that AMP-resistant bacterial mutants display broad cross-resistance to a variety of AMPs with different structures and modes of action. Therefore, routine clinical administration of AMPs to treat bacterial infections may select for resistant bacterial pathogens capable of better evading the innate immune system. The ramifications of therapeutic levels of exposure on the development of AMP resistance and bacterial pathogenesis are not yet understood. This is something that needs to be carefully studied and monitored if AMPs are used in clinical settings. PMID- 27180310 TI - Systems immunology: Beyond antibody titers. AB - Despite the evident success of currently available vaccines to prevent infectious diseases, we still lack a full understanding of the mechanisms by which vaccines induce protective immune responses. Systems immunology applies multifaceted analytical tools to better understand the immune responses to vaccines by deep characterization of the cellular components, regulatory pathways, antibody responses and immune gene profiles with the ultimate goal of identifying the complex cellular, genetic and regulatory factors and mechanisms that contribute to effective and protective immune responses. PMID- 27180311 TI - Impetigo and scabies - Disease burden and modern treatment strategies. AB - Impetigo and scabies both present different challenges in resource-limited compared with industrialised settings. Severe complications of these skin infections are common in resource-limited settings, where the burden of disease is highest. The microbiology, risk factors for disease, diagnostic approaches and availability and suitability of therapies also vary according to setting. Taking this into account we aim to summarise recent data on the epidemiology of impetigo and scabies and describe the current evidence around approaches to individual and community based treatment. PMID- 27180312 TI - Beta-lactamases in Enterobacteriaceae infections in children. AB - Multi-drug resistance in Gram negative bacteria, particularly in Enterobacteriaceae, is a major clinical and public health challenge. The main mechanism of resistance in Enterobacteriaceae is linked to the production of beta lactamase hydrolysing enzymes such as extended spectrum beta-lactamases (ESBL), AmpC beta-lactamases and carbapenemases (Carbapenemase Producing Enterobacteriaceae (CPE)). ESBL and CPE resistance genes are located on plasmids, which can be transmitted between Enterobacteriaceae, facilitating their spread in hospitals and communities. These plasmids usually harbour multiple additional co resistance genes, including to trimethoprim-sulfamethoxazole, aminoglycosides, and fluoroquinolones, making these infections challenging to treat. Asymptomatic carriage in healthy children as well as community acquired infections are increasingly reported, particularly with ESBL. Therapeutic options are limited and previously little used antimicrobials such as fosfomycin and colistin have been re-introduced in clinical practice. Paediatric experience with these agents is limited hence there is a need to further examine their clinical efficacy, dosage and toxicity in children. Antimicrobial stewardship along with strict infection prevention and control practices need to be adopted widely in order to preserve currently available antimicrobials. The future development of novel agents effective against beta-lactamases producers and their applicability in children is urgently needed to address the challenge of multi-resistant Gram negative infections. PMID- 27180313 TI - Examining the July Effect: A National Survey of Academic Leaders in Medicine. AB - BACKGROUND: Whether the "July Effect" affects perspectives or has prompted changes in US Internal Medicine residency programs is unknown. METHODS: We designed a survey-based study to assess views and efforts aimed at preventing harm in July. A convenience sampling strategy (email listserv and direct messages to program leaders via the Electronic Residency Application Service) was used to disseminate the survey. RESULTS: The response rate was 16% (65/418 programs); however, a total of 262 respondents from all 50 states where residency programs are located were included. Most respondents (n = 201; 77%) indicated that errors occur more frequently in July compared with other months. The most common identified errors included incorrect or delayed orders (n = 183, 70% and n = 167, 64%, respectively), errors in discharge medications (n = 144, 55%), and inadequate information exchange at handoffs (n = 143, 55%). Limited trainee experience (n = 208, 79%), lack of understanding hospital workflow, and difficulty using electronic medical record systems (n = 194; 74% and n = 188; 72%, respectively) were reported as the most common factors contributing to these errors. Programs reported instituting several efforts to prevent harm in July: for interns, additional electronic medical record training (n = 178; 68%) and education on handoffs and discharge processes (n = 176; 67% and n = 108; 41%, respectively) were introduced. Similarly, for senior residents, teaching sessions on how to lead a team (n = 158; 60%) and preferential placement of certain residents on harder rotations (n = 103; 39%) were also reported. Most respondents (n = 140; 53%) also solicited specific "July attendings" using a volunteer system or highest teaching ratings. CONCLUSION: Residency programs in Internal Medicine appear to have instituted various changes to mitigate harm in July. Further evaluation to understand the impact of these interventions on trainee education and patient safety is necessary. PMID- 27180315 TI - Traditional Chinese medicine formulas for the treatment of osteoporosis: Implication for antiosteoporotic drug discovery. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Osteoporosis is a chronic epidemic which can leads to enhanced bone fragility and consequent an increase in fracture risk. Traditional Chinese medicine (TCM) formulas have a long history of use in the prevention and treatment of osteoporosis. Antiosteoporotic TCM formulas have conspicuous advantage over single drugs. Systematic data mining of the existing antiosteoporotic TCM formulas database can certainly help the drug discovery processes and help the identification of safe candidates with synergistic formulations. In this review, the authors summarize the clinical use and animal experiments of TCM formulas and their mechanism of action, and discuss the potential antiosteoporotic activity and the active constituents of commonly used herbs in TCM formulas for the therapy of osteoporosis. MATERIALS AND METHODS: The literature was searched from Medline, Pubmed, ScienceDirect, Spring Link, Web of Science, CNKI and VIP database from 1989 to 2015, and also collected from Chinese traditional books and Chinese Pharmacopoeia with key words such as osteoporosis, osteoblast, osteoclast, traditional Chinese medicine formulas to identify studies on the antiosteoporotic effects of TCM formulas, herbs and chemical constituents, and also their possible mechanisms. RESULTS: Thirty-three TCM formulas were commonly used to treat osteoporosis, and showed significant antiosteoporotic effects in human and animal. The herb medicines and their chemical constituents in TCM formulas were summarized, the pharmacological effects and chemical constituents of commonly used herbs in TCM formulas were described in detail. The action mechanisms of TCM formulas and their chemical constituents were described. Finally, the implication for the discovery of antiosteoporotic leads and combinatory ingredients from TCM formulas were prospectively discussed. CONCLUSIONS: Clinical practice and animal experiments indicate that TCM formulas provide a definite therapeutic effect on osteoporosis. The active constituents in TCM formulas are diverse in chemical structure, and include flavonoids, lignans, saponins and iridoid glycosides. Antiosteoporotic mechanism of TCM formulas and herbs involves multi regulatory pathways, such as Wnt/beta-catenin, BMP/Smad, MAPK pathway and RANKL/OPG system. Phytochemicals from TCM formulas and their compositional herb medicines offer great potential for the development of novel antiosteoporotic drugs. The active ingredients in TCM formulas can be developed in combination as potent drugs, which may exhibit better antiosteoporotic effects compared to the individual compound. PMID- 27180314 TI - Effects of low dose ibogaine on subjective mood state and psychological performance. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Root bark from Tabernanthe iboga has been used traditionally in West Africa as a psychoactive substance in religious rituals. In smaller doses it is reported anecdotally to have stimulant properties. AIM OF THE STUDY: To evaluate the influence of a single 20mg ibogaine dose on psychological variables reflecting subjective mood state and a range of cognitive functions. MATERIALS AND METHODS: 21 healthy male volunteers received single 20mg doses of ibogaine after 6 days pretreatment with double-blind paroxetine or placebo. We compared responses to a battery of psychometric tests and subjective mood ratings performed before and 2h after ibogaine dosing, and assessed relationships between changes in test scores and concentrations of active moiety (the sum of molar noribogaine and ibogaine concentrations). Psychological tests were chosen based on responsiveness to opioid and serotonergic ligands. RESULTS: Ibogaine had minimal influence on psychological tests and mood ratings. The ability to selectively ignore distracting spatial information showed some evidence of modulation; however because this effect was limited to the less challenging condition calls into question the reliability of this result. CONCLUSION: We were unable to identify stimulant effects after single 20mg doses of ibogaine. Future research is needed to confirm whether active moiety concentrations impact selective attention abilities while leaving other cognitive functions and mood state unaffected. PMID- 27180316 TI - Knowledge and demand for medicinal plants used in the treatment and management of diabetes in Nyeri County, Kenya. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Non communicable diseases are currently a major health challenge facing humanity. Nyeri County has one of the highest diabetes prevalence in Kenya (12.6%), compared to the country's prevalence of 5.6%. The purpose of the study was to document; diabetes knowledge, medicinal plants and demand for the services of traditional medicine practitioners, in the management and treatment of diabetes. METHODS: A cross-sectional study was carried out in the six constituencies in Nyeri, using pre-tested semi-structured questionnaires. Thirty practicing traditional medicine practitioners were purposively selected for the study. Field observation and identification was carried out on all plants that were cited during the interview. Plant samples were collected and voucher specimen deposited in the University of Nairobi Herbarium in the - School of Biological Sciences. RESULTS: The study revealed 30 plant species in 28 genera and 23 families that are used by the traditional medicine practitioners to treat and manage diabetes. Demand for traditional medicine practitioners' services in the treatment of diabetes is low and often occurs when conventional drugs fail. CONCLUSION: Interaction with the TMPs unveiled significant diversity of potential anti diabetic medicinal plants and in-depth ethnobotanical knowledge that they possessed. Preference for traditional herbal medicine was low despite wide ethnobotanical knowledge in the face of high prevalence of diabetes in the locality. The findings form the basis of pharmacological studies for standardization of the documented ethnomedicine used in the treatment and management of diabetes in the study area. PMID- 27180317 TI - Multicomponent, multitarget integrated adjustment - Metabolomics study of Qizhiweitong particles curing gastrointestinal motility disorders in mice induced by atropine. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Qizhiweitong particles (QZWT) which is derived from the Sinisan decoction in Shang Han Za Bing Lun, composed of Bupleurum chinenis, Paeonia obovata, Citrus aurantium L., Glycyrrhiza uralensis Fisch., Cyperus rotundus and Rhizoma Corydalis is a traditional Chinese medicine (TCM) treating gastrointestinal diseases. It have been used in clinical for years. It have been used in clinical for years. According to previous research, Bupleurum chinenis, Citrus aurantium, Cyperus rotundus in QZWT play the role of promoting gastric peristalsis, which consist of complex chemical constituents. The aim of this study is to probe the multiple effective components with gastrointestinal prokinetic efficacy in QZWT and investigate the multitarget integrated adjustment mechanism of QZWT curing atropine-induced gastrointestinal motility dysfunction mice. MATERIALS AND METHODS: One hundred and thirty two male mice were randomly divided into 11 groups, including control group, model group, Domperidone group, Mosapride group, QZWT group and six components groups. With gastric retention rate, rate of small intestine propulsion, serum content of GAS and MTL as indexes to evaluate the curing effect on gastrointestinal movement disorders caused by atropine in mice. A serum metabonomics method based on the ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) had been established to investigate the mechanism of QZWT and these components, and PCA and PLS-DA have been used to distinguish different groups and found potential biomarkers. RESULTS: Four components from six present good prokinetic effects, including Bupleurum Polysaccharide, Citrus aurantium flavonoid, Citrus aurantium essential oil and Cyperus rotundus flavonoids. These components and QZWT regulate 5 potential biomarkers in the body, and primarily involved in 5 metabolic pathways. These potential biomarkers possess direct or indirect connections, each biomarker regulated by multiple components, each component adjusting multiple targets, and QZWT is nearly the sum of its components. CONCLUSIONS: This experiment deepened our understanding of insufficient gastrointestinal dynamics, confirmed that QZWT treating gastrointestinal disorders was through multicomponent, multitarget ways. These results fully reflect the multiple targets synergy characteristics of TCM. PMID- 27180320 TI - Spontaneous fracture of cranioplastic titanium implants without head trauma in an adult: A case report. AB - INTRODUCTION: The cranioplasty is a classical surgical procedure to repair large skull defects. The prosthesis fracture was one rare complication following cranioplasty, which was only known to happen in traumatic head injury or child growing skull. PRESENTATION OF CASE: In the current report, we documented the first reported case of cranioplasty prosthesis fracture in an adult neurological trauma patient at the proximal pterion point region without head trauma. During the first cranioplasty, due to the cerebromalacia at temporal lobe, patient's temporalis muscle was not stripped from the dura mater and the prosthesis was anchored outside the temporalis muscle. Thus, no screw was used for anchoring the prosthesis at the basitemporal skull. The prosthesis fracture was observed on 12(th)-month post-surgically at the proximal pterion point region. During the second cranioplasty, the temporalis muscle was semi-partitioned from the back due to cerebromalacia recovery and five screws were used to anchor the prosthesis onto the basitemporal skull. The follow-up result was unremarkable on 21(st) month post-second-cranioplasty. DISCUSSION: A dynamic load was generated on the prosthesis due to head-pillow contact during sleeping. Via the parietal tuber temporozygomatic suture line, this inward load generates an outward force at the proximal pterion point region, where became a shearing force locating just right below the lowest screw anchoring in this region. This shearing force eventually led to prosthesis fracture at the proximal pterion point due to the fatigue effect. CONCLUSION: This case presented the importance of prosthesis anchoring location on the skull, especially when temporalis muscle was required to be preserved due to clinical necessity. PMID- 27180319 TI - 'Up-regulation of histone acetylation induced by social defeat mediates the conditioned rewarding effects of cocaine. AB - Social defeat (SD) induces a long-lasting increase in the rewarding effects of psychostimulants measured using the self-administration and conditioned place procedures (CPP). However, little is known about the epigenetic changes induced by social stress and about their role in the increased response to the rewarding effects of psychostimulants. Considering that histone acetylation regulates transcriptional activity and contributes to drug-induced behavioral changes, we addressed the hypothesis that SD induces transcriptional changes by histone modifications associated with the acquisition of place conditioning. After a fourth defeat, H3(K9) acetylation was decreased in the hippocampus, while there was an increase of HAT and a decrease of HDAC levels in the cortex. Three weeks after the last defeat, mice displayed an increase in histone H4(K12) acetylation and an upregulation of histone acetyl transferase (HAT) activity in the hippocampus. In addition, H3(K4)me3, which is closely associated with transcriptional initiation, was also augmented in the hippocampus three weeks after the last defeat. Inhibition of HAT by curcumin (100mg/kg) before each SD blocked the increase in the conditioned reinforcing effects of 1mg/kg of cocaine, while inhibition of HDAC by valproic acid (500mg/kg) before social stress potentiated cocaine-induced CPP. Preference was reinstated when animals received a priming dose of 0.5mg/kg of cocaine, an effect that was absent in untreated defeated mice. These results suggest that the experience of SD induces chromatin remodeling, alters histone acetylation and methylation, and modifies the effects of cocaine on place conditioning. They also point to epigenetic mechanisms as potential avenues leading to new treatments for the long-term effects of social stress on drug addiction. PMID- 27180318 TI - North American Multicenter Volumetric CT Study for Clinical Staging of Malignant Pleural Mesothelioma: Feasibility and Logistics of Setting Up a Quantitative Imaging Study. AB - BACKGROUND: Clinical tumor (T), node, and metastasis staging is based on a qualitative assessment of features defining T descriptors and has been found to be suboptimal for predicting the prognosis of patients with malignant pleural mesothelioma (MPM). Previous work suggests that volumetric computed tomography (VolCT) is prognostic and, if found practical and reproducible, could improve clinical MPM classification. METHODS: Six North American institutions electronically submitted clinical, pathologic, and imaging data on patients with stages I to IV MPM to an established multicenter database and biostatistical center. Two reference radiologists blinded to clinical data independently reviewed the scans; calculated clinical T, node, and metastasis stage by standard criteria; performed semiautomated tumor volume calculations using commercially available software; and submitted the findings to the biostatistical center. Study end points included the feasibility of a multi-institutional VolCT network, concordance of independent VolCT assessments, and association of VolCT with pathological T classification. RESULTS: Of 164 submitted cases, 129 were evaluated by both reference radiologists. Discordant clinical staging of most cases confirmed the inadequacy of current criteria. The overall correlation between VolCT estimates was good (Spearman correlation 0.822), but some were significantly discordant. Root cause analysis of the most discordant estimates identified four common sources of variability. Despite these limitations, median tumor volume estimates were similar within subgroups of cases representing each pathological T descriptor and increased monotonically for each reference radiologist with increasing pathological T status. CONCLUSIONS: The good correlation between VolCT estimates obtained for most cases reviewed by two independent radiologists and qualitative association of VolCT with pathological T status combine to encourage further study. The identified sources of user error will inform design of a follow-up prospective trial to more formally assess interobserver variability of VolCT and its potential contribution to clinical MPM staging. PMID- 27180321 TI - Lateral lung hernia following a low-energy trauma without bony injuries: A case report. AB - INTRODUCTION: Lateral lung hernias are rare, and a herniation of the lung is only reported in the context of high-energy trauma. The predilection site for lung hernias is the anterior thorax. PRESENTATION OF CASE: We present the case of a 82 year-old male, who was admitted with dry cough, shortness of breath and breath dependent left-sided chest pain after a fall. Chest X-ray suggested a pneumonia and subsequently the patient was treated with antibiotics. Due to persistent symptoms after 12days a CT-scan was performed which showed an intercostal lung herniation without fractures. Surgeons were consulted and recommended an operative intervention. Intraoperatively the herniation could be confirmed and necrotic lung tissue was resected. The patient recovered well and was discharged after 10days in good general condition. DISCUSSION: Herniation of lung tissue occurs as a result of injured intercostal muscles in a sudden increase of intrathoracic pressure. Especially lateral herniation is rare because of the additional lateral reinforcement of the thoracic wall by the Serratus muscle. While a conservative approach is possible in asymptomatic hernias and small defect size, surgical intervention is indicated for larger hernias, possible incarceration of lung tissue with resulting infarction and symptoms like chronic pain or respiratory failure. CONCLUSION: For an adequate differential diagnosis of thoracic pain with a history and external signs of a trauma, a CT imaging should be evaluated at an early stage even after a low-energy trauma. An operation is indicated for large defect size and persistent symptoms. PMID- 27180322 TI - Traumatic abdominal wall hernia: A case report and literature review. AB - INTRODUCTION: Traumatic abdominal wall hernia is a rare but serious diagnosis resulting from blunt abdominal trauma. The clinical diagnosis is not usually straightforward and the hernia is often discovered at the time of the surgical exploration for intra-abdominal injuries or by imaging studies. PRESENTATION OF CASE: A 25-year-old obese, restraint, male patient was the victim of a high-speed road traffic accident. Among other injuries, he showed extensive skin maceration and bruising over the lower abdomen and flanks upon presentation, however he did not need any surgical intervention. Contrast-enhanced computed tomography scan of the abdomen and pelvis demonstrated extensive abdominal wall muscular disruption over both flanks with herniation of the right colon. Counselled to follow up in 4 6 weeks to have the hernia surgically repaired, he showed up after 8 months with a large muscular defect resulting in a large hernia containing small and large bowel loops. DISCUSSION: The timing and type of the surgical repair of traumatic abdominal wall hernia depends upon the size of the hernia defect and the presence of associated intra-abdominal injuries. Delayed repair; however, may result in a large defect making primary, non-prosthetic repair impossible and increases the risk of abdominal compartment syndrome after surgical correction. CONCLUSION: Traumatic abdominal wall hernia presents a diagnostic as well as a therapeutic challenge. The therapeutic approach is governed by a multitude of factors emphasizing the need of a patient-tailored, case by case management plan. PMID- 27180323 TI - A case report of symptomatic gallbladder disease in the setting of peritoneal carcinomatosis originating from invasive lobular carcinoma of the breast. AB - INTRODUCTION: Invasive lobular carcinoma is the second most common type of breast cancer, responsible for 5-15 percent of all cases. Peritoneal carcinomatosis secondary to breast cancer is a rare event, frequently resulting in morbidity and mortality. Symptomatic gallbladder disease in the setting of peritoneal carcinomatosis originating from invasive lobular carcinoma of the breast is a very rare event and is not well covered in literature. PRESENTATION OF CASE: A 44year old female patient previously diagnosed with stage IV invasive lobular carcinoma of the left breast with widespread systemic metastases and peritoneal carcinomatosis presented with a three week history of right upper quadrant pain trigged by food intake only, greatly diminishing her quality of life. She had spent almost a year in a progression free disease status but was now suffering from debilitating symptomatic gallbladder disease. Despite the extent of her peritoneal carcinomatosis, she elected to undergo a laparoscopic cholecystectomy. DISCUSSION: We are presenting a rare case of symptomatic gallbladder disease in the setting of peritoneal carcinomatosis secondary to invasive lobular carcinoma. A major concern is tumor load within nearby portal structures. Even though laparoscopic cholecystectomy could be a viable option to treat the condition, it needs to be applied selectively and very cautiously in the respective patient population. CONCLUSION: Symptomatic gallbladder disease in the setting of peritoneal carcinomatosis secondary to invasive lobular carcinoma is an uncommon presentation to surgeons. A diagnostic laparoscopy is the preferred initial evaluation. If deemed feasible, and if the surgeon has the required experience, a laparoscopic cholecystectomy can be undertaken selectively. PMID- 27180324 TI - H2S and cancer: Give credit where credit is due. PMID- 27180326 TI - Alternative programs for synchronizing and resynchronizing ovulation in beef cattle. AB - Fixed-time artificial insemination (FTAI) has been regarded as the most useful method to increase the number of cows inseminated in a given herd. The main treatments for FTAI in beef cattle are based on the use of progesterone-releasing devices and GnRH or estradiol to synchronize follicle wave emergence, with a mean pregnancy per AI (P/AI) around 50%. However, more recent protocols based on GnRH (named 5-day Co-Synch) or estradiol (named J-Synch) that reduce the period of progesterone device insertion and extend the period from device removal to FTAI have been reported to improve P/AI in beef cattle. Furthermore, treatments to resynchronize ovulation for a second FTAI in nonpregnant cows have provided the opportunity to do sequential inseminations and achieve high P/AI in a breeding season, reducing or even eliminating the need for clean-up bulls. In summary, FTAI protocols have facilitated the widespread application of AI in beef cattle, primarily by eliminating the necessity of estrus detection in beef herds. PMID- 27180325 TI - De Ritis (aspartate transaminase/alanine transaminase) ratio as a significant predictor of recurrence-free survival in patients with upper urinary tract urothelial carcinoma following nephroureterectomy. AB - BACKGROUND: To evaluate the prognostic significance of preoperatively assessed aspartate aminotransaminase (AST), alanine aminotransaminase (ALT), and the AST/ALT (De Ritis) ratio in patients with upper urinary tract urothelial carcinoma (UUTUC). METHODS: This study included a total of 109 consecutive patients with clinically localized UUTUC who underwent nephroureterectomy. Effects of preoperative levels of AST, ALT, and the De Ritis ratio in addition to conventional clinicopathological parameters on the extravesical recurrence-free survival (eRFS) in these 109 patients were retrospectively analyzed. RESULTS: Despite the lack of a significant correlation of AST or ALT with any of the factors examined in this study, the elevation of the De Ritis ratio was significantly correlated with several unfavorable parameters, including elderly age, high pathological stage, high tumor grade, and lymphovascular invasion. During the observation period of this series (median = 40.8mo), extravesical disease recurrence developed in 39 (35.8%) of the 109 patients, with a 5-year eRFS rate of 56.8%. Of several factors examined, the tumor location, De Ritis ratio, pathological stage, lymph node metastasis, tumor grade, lymphovascular invasion, surgical margin status, and adjuvant chemotherapy were shown to be significantly correlated with eRFS by univariate analysis. Of these, the De Ritis ratio, pathological stage, lymph node metastasis, and tumor grade were identified as independent predictors of eRFS on multivariate analysis. CONCLUSIONS: These findings suggest that preoperative assessment of the De Ritis ratio may provide useful information with respect to the clinical course of patients with clinically localized UUTUC who are scheduled to be treated with nephroureterectomy. PMID- 27180327 TI - Managing the reproductive performance of beef cows. AB - A reproductively efficient beef cow herd will be fundamental to meeting the protein and specifically, red meat demand of an ever increasing global population. However, attaining a high level of reproductive efficiency is underpinned by producers being cognizant of and achieving many key targets throughout the production cycle and requires considerable technical competency. The lifetime productivity of the beef-bred female commences from the onset of puberty and will be dictated by subsequent critical events including age at first calving, duration of the postpartum interval after successive calvings, conception and pregnancy rate, and ultimately manifested as length of intercalving intervals. In calved heifers and mature cows, the onset of ovarian activity, postpartum is a key event dictating the calving interval. Again, this will be the product mainly of prepartum nutrition, manifested through body condition score and the strength of the maternal bond between cow and calf, though there is increasing evidence of a modest genetic influence on this trait. After the initiation of postpartum ovarian cyclicity, conception and subsequent pregnancy rate is generally a function of bull fertility in natural service herds and heat detection and timing of insemination in herds bred through AI. Cows and heifers should be maintained on a steady plane of nutrition during the breeding season, but the contribution of significant excesses or deficiencies of nutrients including protein and trace elements is likely to be minor where adequate pasture is available. Although increased efforts are being made internationally to genetically identify and select for more reproductively efficient beef cows, this is a more long-term strategy and will not replace the need for a high level of technical efficiency and management practice at farm level. PMID- 27180328 TI - Oocyte pre-IVM with caffeine improves bovine embryo survival after vitrification. AB - Cryopreservation of in vitro produced bovine embryos is associated with significantly reduced survival rates, mainly due to insufficient quality of the embryos. Caffeine supplementation during IVM has been used to delay meiotic resumption and concomitantly also increased embryo quality. Here, we investigated the influence of pre-IVM with caffeine on oocyte maturation, intraoocyte cAMP concentration, developmental competence after IVF, and blastocyst cryotolerance. Oocytes were obtained by slicing of ovaries and were submitted to either 2 hours culture before IVM with or without caffeine (0, 1, 5, 10, 20, 30 mM), or standard IVM (no pre-IVM). Oocytes were in vitro matured and fertilized and zygotes were cultured under standard in vitro conditions until Day 8. Expanded blastocysts derived from either standard control or the 10-mM caffeine treatments were submitted to vitrification. Caffeine delayed meiotic resumption after 9-hour IVM in a concentration-dependent manner. The cAMP levels were similar before and after IVM. Matured oocytes, cleavage, and blastocyst rates were reduced in the 30 mM caffeine concentration and were similar among the other treatment groups. Number and proportion of inner cell mass and trophectoderm cells in blastocysts did not differ among treatments. Forty-eight hours after thawing, hatching rates were higher in the 10-mM caffeine group (73.8%) compared with the standard control (59.7%). Reexpansion rates and total number of cells after 48 hours were similar in both treatments. The ratio of live/total cells was higher in the caffeine treatment. These results suggest that caffeine supplementation before IVM delayed meiotic resumption and improved blastocyst quality shown in higher cryotolerance. PMID- 27180329 TI - Comparative aspects of rodent and nonrodent animal models for mechanistic and translational diabetes research. AB - The prevalence of diabetes mellitus, which currently affects 387 million people worldwide, is permanently rising in both adults and adolescents. Despite numerous treatment options, diabetes mellitus is a progressive disease with severe comorbidities, such as nephropathy, neuropathy, and retinopathy, as well as cardiovascular disease. Therefore, animal models predictive of the efficacy and safety of novel compounds in humans are of great value to address the unmet need for improved therapeutics. Although rodent models provide important mechanistic insights, their predictive value for therapeutic outcomes in humans is limited. In recent years, the pig has gained importance for biomedical research because of its close similarity to human anatomy, physiology, size, and, in contrast to non human primates, better ethical acceptance. In this review, anatomic, biochemical, physiological, and morphologic aspects relevant to diabetes research will be compared between different animal species, that is, mouse, rat, rabbit, pig, and non-human primates. The value of the pig as a model organism for diabetes research will be highlighted, and (dis)advantages of the currently available approaches for the generation of pig models exhibiting characteristics of metabolic syndrome or type 2 diabetes mellitus will be discussed. PMID- 27180330 TI - Lipidomics of equine sperm and seminal plasma: Identification of amphiphilic (O acyl)-omega-hydroxy-fatty acids. AB - Using a nontargeted lipidomics analysis of equine sperm and seminal plasma, we were able to characterize a diverse array of individual lipids including ethanolamine and choline ether lipids and seminolipids essential to membrane raft function. We also detected, for the first time in sperm, the presence of (O-acyl) omega-hydroxy-fatty acids (OAHFA) with up to 52 carbon chain lengths, which were localized to the head and not the tail of sperm. The only previous identification of OAHFAs has been in meibomian glands and their sebaceous secretions. The identities of these lipid amphiphiles were validated both by high-resolution mass spectrometry and by tandem mass spectrometry (<1 ppm mass error), which identified the fatty acid (FA) and hydroxy-FA components of individual OAHFAs. The amphiphilic and surfactant properties of these unique lipids could provide an interface between the complex lipid layers of the acrosome and the aqueous environment of the suspending seminal plasma. The potential roles of OAHFAs in orientation of critical proteins in the acrosomal membrane also remain to be explored with these new findings. Another unique finding of our lipidomics study was that phosphatidylethanolamines with mono- or di-unsaturated FA substitutions are present in seminal plasma but not in sperm suggesting a potential role of these glycerophospholipids in sperm capacitation and protecting sperm cells in the female reproductive tract. In summary, we have identified for the first time, the presence of OAHFAs in sperm and several phosphatidylethanolamines in seminal plasma, suggesting that these complex lipids may play critical roles in sperm function. PMID- 27180331 TI - Behind the scenes of JAC: the British Society for Antimicrobial Chemotherapy. AB - This brief article describes the relationship between the British Society for Antimicrobial Chemotherapy (BSAC) and JAC, and how JAC has directly and indirectly facilitated delivery of the BSAC's charitable objectives over the past 40 years. PMID- 27180332 TI - Sister chromatid exchange test in river buffalo lymphocytes treated in vitro with furocoumarin extracts. AB - Furocoumarin extracts from Psoralea morisiana, the endemic Sardinian legume species, were tested for their mutagenic potential on river buffalo blood cells. The results obtained performing the sister chromatid exchange (SCE) test in blood cultures of five river buffalo calves (exposure to furocoumarins for 72h) and five cows (exposure to furocoumarins for 3h, in the absence and presence of S9 metabolic activator) are reported. Significant differences in mean values of SCEs were observed in cells of calves compared to control cells (unexposed), but no differences in SCE mean values were found between treated and untreated cells of cows in the presence or absence of S9. SCE mean values were much higher in cells of cows (exposed and control) than in cells of calves. Indeed, in calf cells, SCE mean values/cell (+/-SD) were 6.66+/-2.45 in the control and 7.63+/-3.01, 9.03+/ 3.90, 9.53+/-3.60 and 9.99+/-3.41 in treated cells at 50, 100, 200 and 400 ug/ml of furocoumarin extracts, respectively. In cow cells, grown in presence of S9, SCE mean values/cell were 11.49+/-4.78 and 11.65+/-5.19 in treated cells at 100 and 200 ug/ml of furocoumarins and 11.66+/-5.45 in the control. In cow cells grown in absence of S9, SCE mean values were 11.81+/-6.14 in the control and 12.35+/-7.09 and 12.01+/-5.43, respectively, in the presence of 100 and 200 ug/ml of furocoumarins. Despite their higher SCE values in the absence of S9, no statistically significant differences were found when these values were compared with those shown in presence of S9, suggesting no mutagenic action of furocoumarins in cows, at the doses used in this study. PMID- 27180333 TI - Signal Sequence Receptor 2 is required for survival of human melanoma cells as part of an unfolded protein response to endoplasmic reticulum stress. AB - Current therapy approaches in melanoma targeting have met with the development of resistance and tumour recurrence with a more aggressive phenotype. In a quest for alternative therapy targets, we had previously identified Signal Sequence Receptor 2 (SSR2) as a gene with high expression in a subgroup of human primary melanomas. Now we show that SSR2 exerts a prosurvival functionality in human melanoma cells and that high expression levels of SSR2 are associated with an unfavourable disease outcome in primary melanoma patients. Consistent with SSR's role in translocation of proteins from the ribosome across the endoplasmic reticulum (ER) membrane, our data supports induction of SSR2 as a part of the ER stress response. This response included SSR2 upregulation upon development of therapy resistance to BRAF inhibitors, as well as the dependency of cell survival of BRAF inhibitor-resistant melanoma cells on SSR2. Complementary gain and loss of function data showed the Unfolded Protein Response (UPR) to ER stress as an inducer of SSR2 via transcriptional regulation through X-Box Binding Protein 1s (XBP1s) and support an ER stress-UPR-Transcription Factor XBP1s-SSR2 response axis in human melanocytic cells. Together with its dispensability for survival in normal human cells, these data propose SSR2 as a potential therapeutic target in (therapy-resistant) human melanoma. PMID- 27180334 TI - A cautionary approach in transitioning to 'green' energy technologies and practices is required. AB - Renewable energy technologies (wind turbines, solar cells, biofuels, etc.) are often referred to as 'clean' or 'green' energy sources, while jobs linked to the field of environmental protection and energy efficiency are referred to as 'green' jobs. The energy efficiency of clean technologies, which is likely to reduce and/or eliminate reliance on fossil fuels, is acknowledged. However, the potential contribution of green technologies and associated practices to ill health and environmental pollution resulting from consumption of energy and raw materials, generation of waste, and the negative impacts related to some life cycle phases of these technologies are discussed. Similarly, a point is made that the green jobs theme is mistakenly oversold because the employment opportunities generated by transitioning to green technologies are not necessarily safe and healthy jobs. Emphasis is put on identifying the hazards associated with these green designs, assessing the risks to the environment and worker health and safety, and either eliminating the hazards or minimizing the risks as essential elements to the design, construction, operation, and maintenance of green technologies. The perception that it is not always economically possible to consider all risk factors associated with renewable energy technologies at the beginning without hampering their implementation, especially in the poor developing countries, is dismissed. Instead, poor countries are encouraged to start implementing environmentally sound practices while transitioning to green technologies in line with their technological development and overall economic growth. PMID- 27180335 TI - Asbestos exposure and mesothelioma incidence and mortality in Bulgaria. AB - Bulgaria totally banned the import, production and use of asbestos in 2005, but produced and used asbestos products during the last 3-4 decades of the 20th century. The aim of this study was to follow the incidence and mortality of mesothelioma in Bulgaria in relation to past occupational exposures. A literature search between 1960 and 2014 was conducted to obtain information on asbestos consumption, occupational exposure and asbestos-related diseases (ARDs). Data on registered mesotheliomas were provided by the National Cancer Register and data for recognized occupational ARDs were provided by the National Social Security Institute. An increase in the incidence of mesothelioma from 5 to 58 from 1993 to 2013, with 666 cases in the 21-year period, was registered. Incidence, mortality rates, deaths and male-to-female ratios and were lower in comparison to industrialized countries. The increase in mesothelioma incidence is considered as a consequence of more recent production and use of asbestos and asbestos products and the high occupational exposure between 1977 and 1989, while the lower rate of mesothelioma deaths and male-to-female ratio need to be investigated further. PMID- 27180336 TI - Unusual phenotype of congenital adrenal hyperplasia (CAH) with a novel mutation of the CYP21A2 gene. AB - Gonadotropin independent sexual precocity (SP) may be due to congenital adrenal hyperplasia (CAH), and its timing usually depends on the type of mutation in the CYP21A2 gene. Compound heterozygotes are common and express phenotypes of varying severity. The objective of this case report was to investigate the hormonal pattern and unusual genetic profile in a 7-year-old boy who presented with pubic hair, acne, an enlarged phallus, slightly increased testicular volume and advanced bone age. Clinical, hormonal and genetic studies were undertaken in the patient as well as his parents. We found elevated serum 17-hydroxyprogesterone (17-OHP) and androstenedione that were suppressed with dexamethasone, and elevated testosterone that actually rose after giving dexamethasone, indicating activity of the hypothalamic-pituitary-gonadal (HPG) axis. An initial search for common mutations was negative, but a more detailed genetic analysis of the CYP21A2 gene revealed two mutations including R341W, a non-classical mutation inherited from his mother, and g.823G>A, a novel not previously reported consensus donor splice site mutation inherited from his father, which is predicted to be salt wasting. However, the child had a normal plasma renin activity. He was effectively treated with low-dose dexamethasone and a GnRH agonist. His father was an unaffected carrier, but his mother had evidence of mild non-classical CAH. In a male child presenting with gonadotropin independent SP it is important to investigate adrenal function with respect to the androgen profile, and to carry out appropriate genetic studies. PMID- 27180338 TI - Role of hippocampal activity-induced transcription in memory consolidation. AB - Experience-dependent changes in the strength of connections between neurons in the hippocampus (HPC) are critical for normal learning and memory consolidation, and disruption of this process drives a variety of neurological and psychiatric diseases. Proper HPC function relies upon discrete changes in gene expression driven by transcription factors (TFs) induced by neuronal activity. Here, we describe the induction and function of many of the most well-studied HPC TFs, including cyclic-AMP response element binding protein, serum-response factor, AP 1, and others, and describe their role in the learning process. We also discuss the known target genes of many of these TFs and the purported mechanisms by which they regulate long-term changes in HPC synaptic strength. Moreover, we propose that future research in this field will depend upon unbiased identification of additional gene targets for these activity-dependent TFs and subsequent meta analyses that identify common genes or pathways regulated by multiple TFs in the HPC during learning or disease. PMID- 27180337 TI - A novel splice site mutation in the GNPTAB gene in an Iranian patient with mucolipidosis II alpha/beta. AB - Mucolipidosis type II alpha/beta (ML II alpha/beta) and mucolipidosis type III alpha/beta (ML III alpha/beta) have been shown to be caused by an absence or reduced level of uridine diphosphate (UDP)-N-acetylglucosamine-1 phosphotransferase enzyme (EC 2.7.8.17) activity, respectively. Both disorders are caused by mutations in the GNPTAB gene and are inherited in an autosomal recessive manner. Here we report a 2-year-old female patient being diagnosed as a case of ML II alpha/beta due to coarse face, severe developmental delay, multiple dysostosis, noticeable increase of multiple lysosomal enzymes activity in plasma and normal acid mucopolysaccharides in urine. Mutational analysis of the GNPTAB gene has revealed a novel homozygous mutation in the patient (c.3250-2A>G) with both parents being heterozygote. Transcript analyses showed that this novel splice site mutation leads to exon 17 skipping and a frameshift afterwards (p.P1084_R1112del F1113Vfs*1). Consequently, we confirmed the association of this mutation with ML II alpha/beta. Our finding expands the number of reported cases of this rare metabolic disorder and adds to the GNPTAB mutation database. PMID- 27180339 TI - Cosmic ray (neutron) activity and air pollution nanoparticles - cardiovascular disease risk factors - separate or together? AB - BACKGROUND: In the last decade, a number of studies were published showing links between cardiovascular events such as stroke (CVA), acute myocardial infarction (AMI), sudden cardiac death (SCD) and cosmic ray activity (CRA) marker neutron activity on the Earth's surface (imp/min). A number of concomitant studies described air pollution fine particles as a similar risk factor. It is not clear which way each of the mentioned factors acts on the way of affecting the human body. The aim of this study is to present separate data of these two factors as risk factors and to discuss the possibility of seeing the nanoparticles polluting our air as carriers of neutrons on their way to the human cardiovascular system. METHODS: Many studies of our groups and groups studying air pollution effects were revised, and the possibility of combined action of both factors was considered. RESULTS: It is known that neutrons on the Earth surface are the markers of CRA. CRA is inversely related to space weather parameters such as solar (SA) and geomagnetic activity. The presumed way of biological action of neutrons is connection with H+ and, as protons, attack on our cells and tissues. The way of action of nanoparticles is explained by specific physical and chemical action of the materials they represent. It is a strong possibility that one way to connect H radicals in the human body is that particles are neutron carriers and can be absorbed in different parts of the body and then affect the systems of human body. CONCLUSIONS: The combined action of CRA (neutron) activity is a possible way of affecting the environment. The precise mechanism of this cooperative action demands additional studies. PMID- 27180340 TI - Effects of nicotine in the presence and absence of vitamin E on morphology, viability and osteogenic gene expression in MG-63 osteoblast-like cells. AB - BACKGROUND: Evidence shows that oxidative stress induced by nicotine plays an important role in bone loss. Vitamin E with its antioxidative properties may be able to reverse the effects of nicotine on bone. This study aimed to assess the effects of nicotine in the presence and absence of vitamin E on morphology, viability and osteogenic gene expression in MG-63 (osteosarcoma) human osteoblast like cells. METHODS: We treated the cells with 5 mM nicotine. The viability and morphology of cells were evaluated respectively using the 3-(4,5-dimethylthiazol 2-yl)-2,5-diphenyl tetrazolium (MTT) and crystal violet assays. The effect of nicotine on osteogenic gene expression in MG-63 cells was assessed by real-time reverse-transcription polymerase chain reaction of osteoblast markers, namely, alkaline phosphatase, osteocalcin and bone sialoprotein. RESULTS: The results revealed that survival and proliferation of MG-63 cells were suppressed following exposure to nicotine, and cytoplasm vacuolization occurred in the cells. Nicotine significantly down-regulated the expression of osteogenic marker genes. Such adverse effects on morphology, viability and osteogenic gene expression of MG-63 cells were reversed by vitamin E therapy. CONCLUSIONS: In conclusion, vitamin E supplementation may play a role in proliferation and differentiation of osteoblasts, and vitamin E can be considered as an anabolic agent to treat nicotine-induced bone loss. PMID- 27180341 TI - Oral administration of green plant-derived chemicals and antioxidants alleviates stress-induced cellular oxidative challenge. AB - BACKGROUND: This study examined the efficacy of the combination antioxidant, Formula 42 (F42), on cellular stress indicators in animal and human models of stress-induced oxidative stress. METHODS: A sub-chronic psychological stress model in rodents was used to induce stress and oxidative stress indicators over a 10-day period during which animals received oral doses of F42 or water. Following treatment, body weight, plasma stress hormone corticosterone, and oxidative capacity were evaluated. In healthy human subjects, a randomized double-blind crossover study was used to examine the antioxidant effect of F42 or placebo in an exercise-induced oxidative stress model. Erythrocyte and plasma oxidative status was evaluated using the fluorescent activation of 2',7'-dichlorofluorescin (DCF) as an indicator. RESULTS: Oral administration of F42 reduced the corticosterone response to acute stress compared to vehicle but did not differ at the conclusion of the 10-day study. However, F42 administration did reduce stress induced growth restriction and alleviate DCF activation in circulating erythrocytes by approximately 10% following 10 days of stress exposure. Oral administration of F42 also significantly reduced DCF activation by approximately 10% in healthy human subjects undergoing exercise-induced oxidative stress. CONCLUSIONS: Oral administration of F42 in rodents produces transient reductions in stress hormones and reduces stress indicators following sub-chronic psychological stress exposure. In humans, F42 acts as an early and potent antioxidant capable of scavenging free radicals within 30 min of ingestion. PMID- 27180342 TI - Circulating microRNAs as a Novel Class of Potential Diagnostic Biomarkers in Neuropsychiatric Disorders. AB - Neuropsychiatric diseases, such as schizophrenia, bipolar disorder (BD), major depressive disorder (MDD) and autism spectrum disorder (ASD), are a huge burden on society, impairing the health of those affected, as well as their ability to learn and work. Biomarkers that reflect the dysregulations linked to neuropsychiatric diseases may potentially assist the diagnosis of these disorders. Most of these biomarkers are found in the brain tissue, which is not easily accessible. This is the challenge for the search of novel biomarkers that are present in various body fluids, including serum or plasma. As a group of important endogenous small noncoding RNAs that regulate gene expression at post transcriptional level, microRNAs (miRNAs) play a crucial role in many physiological and pathological processes. Previously, researchers discovered that miRNAs contribute to the neurodevelopment and maturation, including neurite outgrowth, dendritogenesis and dendritic spine formation. These developments underline the significance of miRNAs as potential biomarkers for diagnosing and prognosing central nervous system diseases. Accumulated evidence indicates that there are considerable differences between the cell-free miRNA expression profiles of healthy subjects and those of patients. Therefore, circulating miRNAs are likely to become a new class of noninvasive, sensitive biomarkers. Despite the fact that little is known about the origin and functions of circulating miRNAs, their essential roles in the clinical diagnosis and prognosis of neuropsychiatric diseases make them attractive biomarkers. In this review we cover the increasing amounts of dataset that have accumulated in the last years on the use of circulating miRNAs and their values as potential biomarkers in most areas of neuropsychiatric diseases. PMID- 27180343 TI - Heart Rate Variability as a Method for Assessment of the Autonomic Nervous System and the Adaptations to Different Physiological and Pathological Conditions. AB - The autonomic nervous system controls the smooth muscles of the internal organs, the cardiovascular system and the secretory function of the glands and plays a major role in the processes of adaptation. Heart rate variability is a non invasive and easily applicable method for the assessment of its activity. The following review describes the origin, parameters and characteristics of this method and its potential for evaluation of the changes of the autonomic nervous system activity in different physiological and pathological conditions such as exogenous hypoxia, physical exercise and sleep. The application of heart rate variability in daily clinical practice would be beneficial for the diagnostics, the outcome prognosis and the assessment of the effect of treatment in various diseases. PMID- 27180344 TI - Osteoporosis: Therapeutic Options. AB - The definition of osteoporosis was originally formulated at a conference of the World Health Organization (WHO) in 1993 as 'a systemic skeletal disease characterized by decreased bone mass and altered micro-architecture of bone tissue, leading to enhanced bone fragility and risk of fractures'. Osteoporosis is characterized by low bone mineral density (BMD) and loss of the structural and bio-mechanical properties that are required to maintain bone homeostasis. This review aims to address the currently available options in prevention and treatment of osteoporosis. Management of osteoporosis includes non pharmacological treatment - diet rich of calcium and vitamin D, healthy lifestyle, proper exercise plan, and pharmacological therapy. Combination of non pharmacological and pharmacological treatment options have to be considered for prevention of osteoporosis and minimization of the risk of fractures. Given the heterogeneity of osteoporosis syndrome and lack of significant number of comparative studies, the choice of a pharmacological agents should be individualized. PMID- 27180345 TI - Epidermal Growth Factor Receptor Activating Mutations in Squamous Histology of Lung Cancer Patients of Southern Bulgaria. AB - There is only limited data on the prevalence of epidermal growth factor receptor (EGFR) activating mutations in squamous cell carcinomas and adenosquamous carcinomas of the lung in patients of the Southern Bulgarian region and the efficacy of EGFR tyrosine kinase inhibitors. AIM: Previous reports for Bulgarian population showed high incidence of EGFR mutations in the squamous cell carcinomas, so we set the goal to investigate their frequency in Southern Bulgaria, after precise immunohistochemical verification of lung cancers. MATERIALS AND METHODS: Two hundred and thirty-six lung carcinomas were included in this prospective study. All biopsies were initially analysed with p63, TTF1, Napsin A, CK7, CK34betaE12, synaptophysin, CK20 and CDX2. Two hundred and twenty five non-small cell lung carcinomas were studied with real-time PCR technology to assess the status of the EGFR gene. RESULTS: We detected 132 adenocarcinomas (58.7%), 89 squamous cell carcinomas (39.2%), 4 adenosquamous carcinomas (1.8%), 9 large cell neuroendocrine carcinomas (3.8%) and 2 metastatic colorectal adenocarcinomas (0.8%). Activating mutations in the EGF receptor had 3 out of 89 squamous cell carcinomas (3.37%). We have established mutations in L858R, deletion in exon 19 and rare mutation in S7681. One out of four adenosquamous carcinomas had a point mutation in the L858R (25%). CONCLUSIONS: The frequency of EGFR mutations we found in lung squamous cell carcinomas in a Southern Bulgarian region is lower than that in European countries. Ethnic diversity in the region does not play role of an independent predictive factor in terms of mutation frequency. PMID- 27180346 TI - 25 Hydroxyvitamin D and Cytokines in Multiple Sclerosis. AB - INTRODUCTION: Clinical trials of patients with multiple sclerosis (MS) have produced inconsistent results for the profile of cytokine secretion in serum and cerebrospinal fluid in patients with multiple sclerosis during periods of relapse and remission. Epidemiological and clinical observations data reveal an association of the changes in vitamin D serum concentration with the risk of developing MS. AIM: To evaluate changes in serum concentrations of 25(OH)D, IL17, IFN-gamma, TGFbeta1, IL4, IL10 in relapse and remission and their correlation with the severity of disability. PATIENTS AND METHODS: Fifty-three persons (30 clinically healthy controls and 23 patients with relapsing-remitting multiple sclerosis) living between 41 degrees and 42 degrees northern latitude were registered during the astronomical winter period (October 2012- May 2013). Patients were diagnosed according to Mc Donald 2010 criteria. The degree of neurological deficit was assessed by EDSS. Serum concentrations of 25(OH)D (nmol/l) and cytokines (pg/ml) were tested by ELISA - once for controls and twice for patients (during relapse and remission). RESULTS: In the studied population average levels of 25(OH)D were close to insufficiency, most pronounced in patients in relapse, as differences were not statistically significant. A reverse correlation was found between the levels of 25(OH)D and the deficit in relapse and remission. Concentrations of TGFbeta1 significantly increased in remission compared with exacerbation and controls. Serum level of IL4 was significantly lower in relapse compared with controls. In remission there was a marked tendency of increase compared with exacerbation. During clinical improvement IL17 and IFN gamma tended to decrease compared to the average levels in relapse. In both periods, the average concentrations of IFN-gamma in patients were significantly lower compared with controls. No statistically significant differences were found comparing cytokine changes with those of 25(OH)D and deficit. CONCLUSION: Persistent cytokine imbalance in patients compared with controls is a marker for Th1-mediated CNS demyelination. Anti-inflammatory TGFbeta1, IL4 are indicators of immune response intensity. The deficit severity does not depend on changes of the tested cytokines, but correlates with 25(OH)D levels during periods of relapse and remission. PMID- 27180348 TI - Hearing Loss in Patients with Shunt-Treated Hydrocephalus. AB - Hearing loss is a common manifestation of the long-term complications in patients with shunt treated hydrocephalus along with motor development disturbance, cognitive and visual impairment, epilepsy and endocrine disorders. The aim of the present study was to investigate the alterations of hearing in patients with shunt treated hydrocephalus of non-tumor etiology and at least one year after implantation of ventriculo-peritoneal shunt, as well as their impact on the quality of life of patients. The study included 70 patients (age range 1.25 years - 21.25 years) with shunted non-tumor hydrocephalus and at least one year after placement of the shunt system. Hearing alterations were proved by measuring the brainstem auditory evoked potentials (BAEP) for children up to 5 years of age and children with mental retardation; audiograms was used for children older than 5 years with normal neuro-psychological development (NPD). Of the 70 studied patients 17 (24%) had hearing loss (10 bilateral and 7-unilateral) and all of them had sensorineural hearing loss, which is associated with low weight at birth, posthemorrhagic hydrocephalus and brainstem symptoms at the time of diagnosis of hydrocephalus. Hearing pathology was found more often in shunt treated patients with NPD retardation, poor functional status and low quality of life. Children with shunt-treated hydrocephalus have hearing loss of sensorineural type. Children with brain stem symptomatology at diagnosing hydrocephalus and children with post-hemorrhagic hydrocephalus show higher risk of hearing loss. Children with shunted hydrocephalus and hearing loss show lower NPD, lower quality of life and lower functional status. PMID- 27180347 TI - Discrepancies between Spectral Domain Optical Coherence Tomography and Fluorescein Angiography in Detecting Uveitic Macular Edema. AB - AIM: To compare spectral-domain optical coherence tomography (SD-OCT) with fluorescein angiography (FA) in detecting macular edema in patients with uveitis and analyse discrepancies in the findings obtained by the two methods. METHODS: The study included 133 eyes from 117 patients with uveitis that had SD-OCT (RTVue 100/ Optovue) and FA (Topcon TRC 50DX) scans performed to detect or rule out macular edema. RESULTS: Macular edema was found in 57 (42.9%) of the 133 surveyed eyes. In 37 eyes (27.8%) macular edema was confirmed by both imaging methods. In 17 eyes (12.8%) macular edema was detected on SD-OCT but not on FA;in 15 eyes of these the edema was diffuse, and in 2 eyes - serous retinal detachment was verified in the macular area. Focal macular edema was detected on FA in three eyes (2.3%) in which SD-OCT showed normal finding. In 76 eyes (57.1%) no pathological changes in the macula were observed on both SD-OCT and FA. Kappa coefficient was 0.675 at p < 0.001. The agreement rate between the two methods calculated using Kendall's tau-b was 0.693 at p < 0.001. CONCLUSION: Fluorescein angiography and spectral domain optical coherence tomography are highly sensitive methods used in detecting macular edema in patients with uveitis, but they might fail to be efficient in this if used independently. Optical coherence tomography is a more informative method, especially in diagnosing diffuse macular edema. PMID- 27180349 TI - Physical Improvement and Biological Maturity of Young Athletes (11-12 Years) with Systematic Training. AB - AIM: The aim of this study was to investigate the influence of systematic training in physical growth and biological maturity in prepubertal males and estimate how this affects the physical growth and skeletal maturity. MATERIALS AND METHODS: 177 primary school students of the fifth and sixth grade, from schools in Alexandroupolis, participated voluntarily in our study. Questionnaires were used in order to measure physical activity levels. The subjects were subdivided into two groups; control group (prepubertal, whose physical activity was the physical education of their school and which had never participated in systematic training, n = 95) and experimental group (prepubertal, whose weekly physical activity included physical education in their schools and additionally 3 4 training units organized training in various sports clubs in the city, n = 82). The following parameters were recorded: biological age measured by determination of skeletal age; bone density measured by ultrasound methods; anthropometric and morphological features such as height, body composition, selected diameters, circumferences and skinfolds; motor ability features. RESULTS: The experimental group exhibited older biological age (p = 0.033), higher bone density (p < 0.001), lower BMI and body fat (p < 0.001), better anthropometric features and higher performance throughout all motor ability tests (p < 0.05), compared to the control group. CONCLUSION: The present study demonstrates that systematic physical activity has a positive effect on both the physical and biological maturity of pre-pubertal children. This effect is mainly expressed in bone strengthening as a result of the increased bone density and in improvement of the kinetic skills of pupils who participated in organized extracurricular sport activities. PMID- 27180350 TI - Evaluation of Acute Exogenous Hypoxia Impact on the Fraction of Exhaled Nitric Oxide in Healthy Males. AB - INTRODUCTION: Exogenous hypoxia increases ventilation and contracts the pulmonary vessels. Whether those factors change the values of nitric oxide in exhaled air has not yet been evaluated. OBJECTIVE: To examine the effect of exogenous normobaric hypoxia on the values of the fraction of nitric oxide in exhaled breath (FeNO). Subjects and Methods: Twenty healthy non-smoker males at mean age of 25.4 (SD = 3.7) were tested. The basal FeNO values were compared with those at 7 min. and 15 min. after introducing into the hypoxic environment (hypoxic tent), imitating atmospheric air with oxygen concentration corresponding to 3200 m above sea level. Exhaled breath temperature was measured at baseline and at 10-12 min. of the hypoxic exposition. Heart rate and oxygen saturation were registered by pulse-oximetry. RESULTS: All the subjects had FeNO values in the reference range. The mean baseline value was 14.0 +/- 3.2 ppb, and in hypoxic conditions - 15.5 +/ 3.8 ppb (7 min.) and 15.3 +/- 3.6 ppb (15 min.), respectively, as the elevation is statistically significant (p = 0.011 and p = 0.008). The values of exhaled breath temperature were 33.79 +/- 1.55 degrees S and 33.87 +/- 1.83 degrees S (p = 0.70) at baseline and in hypoxic conditions, respectively. Baseline oxygen saturation in all subjects was higher than that, measured in hypoxia (96.93 +/- 1.29% vs. 94.27 +/- 2.53%; p < 0.001). CONCLUSIONS: Exogenous hypoxia leads to an increase of FeNO values, but does not affect the exhaled breath temperature. PMID- 27180351 TI - The Acute Effect of the Antioxidant Drug U-74389G on Red Blood Cell Distribution Width Levels During Hypoxia Reoxygenation Injury in Rats. AB - The AIM of this experimental study was to evaluate the effect of the antioxidant drug "U-74389G" in a rat model of hypoxia reoxygenation (HR) using the previously established protocol. Effects of treatment were evaluated by mean red blood cell distribution width (RDW) levels. MATERIALS AND METHODS: 40 rats of a mean weight of 231.875 g were employed in the study. RDW levels were determined at 60 min (groups A and C) and at 120 min (groups B and D) after starting the reoxygenation. Groups A and B received no drugs, whereas rats from groups C and D were administered with U-74389G. RESULTS: demonstrated that U-74389G administration significantly decreased the RDW levels by 4.96% + 2.27% (p = 0.0175). Reoxygenation time non-significantly decreased the RDW levels by 0.27% + 2.41% (p = 0.8889). Together, U-74389G administration and reoxygenation time non significantly decreased the RDW levels by 2.54% + 1.39% (p = 0.0679). CONCLUSIONS: U-74389G administration particulary in concert without reperfusion declines the RDW levels even within the short - time context of 1.5 hours reperfusion. PMID- 27180352 TI - Clinical Impact of Dental Adhesives on Postoperative Sensitivity in Class I and Class II Resin-Composite Restorations. AB - BACKGROUND: Self-etch adhesives are believed to prevent postoperative sensitivity when used under posterior resin-based composite restorations. STUDY OBJECTIVE: A hypothesis that a one-step self-etch adhesive (1-SEA) would result in less postoperative sensitivity than a three-step etch-and-rinse adhesive (3-E&RA) was tested. PATIENTS AND METHODS: One hundred restorations were placed with a 1-SEA and 100 restorations with a 3-E&RA. Teeth were restored with Filtek Supreme nanofilled resin-composite and were evaluated for sensitivity to cold and masticatory forces at baseline, 7 days, 14 days, 30 days, and 6 months postoperatively. Vitality test scores of the teeth were recorded at the same periods. RESULTS: The evaluation of cold sensitivity intensity (VAS score) for all observation periods in both restoration groups did not reveal any statistical significance. The differences in the response time to cold stimulation (0 - 15 sec) for the restorations made with a 1-SEA and those made with a separate etch step are statistically insignificant. There are no significant differences in the vitality of the restored teeth at intra- or inter-group comparison. The statistical analysis revealed significant differences in postoperative sensitivity to masticatory forces at postoperative day 14 and day 30 in the 3 E&RA group. CONCLUSIONS: Postoperative sensitivity depends on the type of dentin adhesive used. More intensive complaints of postoperative sensitivity were recorded under masticatory forces at postoperative day 14 and day 30 in 3-E&RA in comparison with 1-SEA. PMID- 27180353 TI - Clinical Effect of Dental Adhesive on Marginal Integrity in Class I And Class II Resin-Composite Restorations. AB - BACKGROUND: Dental adhesives are believed to influence marginal adaptation and marginal discoloration when used under posterior resin-based composite restorations. Studies on the latest adhesive systems reveal that the group of the three-step etch-and-rinse adhesive (3-E&RA) and the one-step self-etch adhesive (1-SEA) have entirely different bonding mechanisms, as well as different bond strength and resistance to chemical, thermal and mechanical factors. STUDY OBJECTIVES: A hypothesis that a 1-SEA would result in greater enamel marginal discoloration and poorer marginal adaptation than a 3-E&RA was tested. MATERIAL AND METHODS: One hundred restorations were placed with a 1-SEA and 100 restorations with a 3-E&RA. Teeth were restored with Filtek Supreme nanofilled resin-composite and were evaluated for marginal adaptation and marginal discoloration at baseline, and 6 months, 12 months, and 36 months postoperatively. RESULTS: The statistical analysis revealed significant differences in marginal integrity between test groups. The 1-SEA resulted in greater enamel marginal discoloration and poorer marginal adaptation than the 3 E&RA at any recall time. CONCLUSIONS: Marginal adaptation and marginal discoloration depend on the type of dentin adhesive used. The restorations with Filtek Supreme and Scotchbond MP are better than the restorations with Adper Prompt L-Pop with regard to the marginal adaptation and marginal discoloration at 6-, 12- and 36-month evaluations. PMID- 27180354 TI - Application of Ultrasonic Devices in Management of Periodontal Lesions - Bone Response in a Case of a Tooth with Poor Treatment Prognosis. AB - BACKGROUND: Surgical treatment of odontogenic jaw cysts may include one of the following four basic methods: enucleation, marsupialization, staged combination of marsupialization and enucleation, or enucleation with curettage. Enucleation/cystectomy, alone or combined with other procedures, is the preferred choice of treatment. OBJECTIVE: The aim of the case report was to present the outcome of an ultrasound-assistant periapical cystectomy in a frontal upper tooth with indications for extraction. RESULTS: Postoperative recovery was uneventful. The functional result was satisfactory. On the follow-up X-rays a reduction of the intraosseous defect by a new bone formation could be observed. CONCLUSION: We found ultrasonic surgery to be a promising approach for safe and effective odontogenic jaw cyst removal reducing the risk of its recurrence. PMID- 27180355 TI - Polypharmacy May Be the Cause of Acute Lithium Intoxication at the Second Day of Treatment. AB - Lithium is frequently used as a mood stabilizer in patients with mood disorders. Lithium has a narrow therapeutic index and high toxicity. Predisposing factors for intoxication are advanced age, diet disturbances, comorbid medical conditions affecting heart, kidneys or central nervous system and polypharmacy. CASE REPORT: Here we present a case of a 74-year-old woman with a history of Parkinson's disease, hypertension and bipolar disorder. She was using quetiapine, valsartan with hydrochlorothiazide and levodopa with carbidopa. She presented with altered mental status and muscle rigidity. The patient was admitted with acute lithium intoxication after her second dose of treatment. Blood lithium level increased to 3.58 mEq/L. The woman was hospitalized in the Internal Medicine Intensive Care Unit. With hydration, her symptoms resolved and her lithium level returned to normal after 118 hours. CONCLUSIONS: Prescribing physicians and emergency room physicians should be aware of conditions which may cause a decreased threshold for intoxication. PMID- 27180356 TI - Burden of Sleep Disturbance Due to Traffic Noise in Bulgaria. AB - BACKGROUND: Sleep disturbance is a risk factor for somatic, psycho-social and spiritual dysfunction. It is also arguably the most deleterious effect of traffic noise pollution. Quantification of its burden is an anchor element of environmental policy making but no data are currently available for Bulgaria where the preponderance of dangerous nighttime noise exposure is highest in Europe. AIM: The aim of this study was to quantify the socio-economic burden of severe sleep disturbance due to traffic noise (road, aircraft and railway) in Bulgaria. MATERIAL AND METHODS: The official World Health Organization methodology used in Europe was applied in order to estimate this annual loss expressed as disability-adjusted life-years (DALYs) and their corresponding monetary value (assuming ? 12 000 per DALY). RESULTS: Results showed that severe sleep disturbance due to all traffic sources was associated conservatively with 15 468 DALYs (8 839 - 22 097) and ? 185 615 861 (? 106 066 206 - ? 265 165 516) lost in 2012, with road traffic being the single most important noise source. CONCLUSION: In conclusion, severe sleep disturbance due to traffic noise bears a heavy environmental and socio-economic burden in Bulgaria which prompts vigorous political action and greater involvement in environmental research. In order to increase the accuracy of future burden of disease analyses other studies would need to establish exposure-response functions based on population-based socio acoustic surveys in the country. PMID- 27180357 TI - Tetraspanin 8 is an interactor of the metalloprotease meprin beta within tetraspanin-enriched microdomains. AB - Meprin beta is a dimeric type I transmembrane protein and acts as an ectodomain sheddase at the cell surface. It was shown that meprin beta cleaves the amyloid precursor protein (APP), thereby releasing neurotoxic amyloid beta peptides and implicating a role of meprin beta in Alzheimer's disease. In order to identify non-proteolytic regulators of meprin beta, we performed a split ubiquitin yeast two-hybrid screen using a small intestinal cDNA library. In this screen we identified tetraspanin 8 (TSPAN8) as interaction partner for meprin beta. Since several members of the tetraspanin family were described to interact with metalloproteases thereby affecting their localization and/or activity, we hypothesized similar functions of TSPAN8 in the regulation of meprin beta. We employed cell biological methods to confirm direct binding of TSPAN8 to meprin beta. Surprisingly, we did not observe an effect of TSPAN8 on the catalytic activity of meprin beta nor on the specific cleavage of its substrate APP. However, both proteins were identified being present in tetraspanin-enriched microdomains. Therefore we hypothesize that TSPAN8 might be important for the orchestration of meprin beta at the cell surface with impact on certain proteolytic processes that have to be further identified. PMID- 27180358 TI - Tetraspanin 8 is an interactor of the metalloprotease meprin beta within tetraspanin-enriched microdomains. AB - Meprin beta is a dimeric type I transmembrane protein and acts as an ectodomain sheddase at the cell surface. It has been shown that meprin beta cleaves the amyloid precursor protein (APP), thereby releasing neurotoxic amyloid beta peptides and implicating a role of meprin beta in Alzheimer's disease. In order to identify non-proteolytic regulators of meprin beta, we performed a split ubiquitin yeast two-hybrid screen using a small intestinal cDNA library. In this screen we identified tetraspanin 8 (TSPAN8) as interaction partner for meprin beta. As several members of the tetraspanin family were described to interact with metalloproteases thereby affecting their localization and/or activity, we hypothesized similar functions of TSPAN8 in the regulation of meprin beta. We employed cell biological methods to confirm direct binding of TSPAN8 to meprin beta. Surprisingly, we did not observe an effect of TSPAN8 on the catalytic activity of meprin beta nor on the specific cleavage of its substrate APP. However, both proteins were identified as present in tetraspanin-enriched microdomains. Therefore we hypothesize that TSPAN8 might be important for the orchestration of meprin beta at the cell surface with impact on certain proteolytic processes that have to be further identified. PMID- 27180359 TI - The clear and dark sides of water: influence on the coiled coil folding domain. AB - The essential role of water in extra- and intracellular coiled coil structures of proteins is critically evaluated, and the different protein types incorporating coiled coil units are overviewed. The following subjects are discussed: i) influence of water on the formation and degradation of the coiled coil domain together with the stability of this conformer type; ii) the water's paradox iii) design of coiled coil motifs and iv) expert opinion and outlook is presented. The clear and dark sides refer to the positive and negative aspects of the water molecule, as it may enhance or inhibit a given folding event. This duplicity can be symbolized by the Roman 'Janus-face' which means that water may facilitate and stimulate coiled coil structure formation, however, it may contribute to the fatal processes of oligomerization and amyloidosis of the very same polypeptide chain. PMID- 27180360 TI - Recent advances in the characterization of Crl, the unconventional activator of the stress sigma factor sigmaS/RpoS. AB - The bacterial RNA polymerase (RNAP) holoenzyme is a multisubunit core enzyme associated with a sigma factor that is required for promoter-specific transcription initiation. Besides a primary sigma responsible for most of the gene expression during active growth, bacteria contain alternative sigma factors that control adaptive responses. A recurring strategy in the control of sigma factor activity is their sequestration by anti-sigma factors that occlude the RNAP binding determinants, reducing their activity. In contrast, the unconventional transcription factor Crl binds specifically to the alternative sigma factor sigmaS/RpoS, and favors its association with the core RNAP, thereby increasing its activity. sigmaS is the master regulator of the general stress response that protects many Gram-negative bacteria from several harmful environmental conditions. It is also required for biofilm formation and virulence of Salmonella enterica serovar Typhimurium. In this report, we discuss current knowledge on the regulation and function of Crl in Salmonella and Escherichia coli, two bacterial species in which Crl has been studied. We review recent advances in the structural characterization of the Crl-sigmaS interaction that have led to a better understanding of this unusual mechanism of sigma regulation. PMID- 27180361 TI - Dermatoses Following Nepal Earthquake 2015. PMID- 27180362 TI - Outcome of Titanium Elastic Intramedullary Nail in the Treatment of Shaft of Femur Fracture in Children. AB - Background Femoral-shaft fractures are among the most common fractures of the lower extremity in children. There are several different options for treating femoral-shaft fractures in children. Elastic stable intramedullary nailing (ESIN) has become the standard treatment for fractures of shaft of femur in children for reasons including mini-invasive surgery, no need for casting, early mobilization and discharge as well as growing concerns toward cost-effectiveness. Objective To demonstrate the effectiveness of intramedullary fixation of fracture shaft of femur in skeletally immature children using the titanium elastic intramedullary nails. Method Forty children who underwent fixation with titanium intramedullary nails because of fracture of shaft of femur (Winquist and Hansen type 1 and 2) were reviewed. There were 60% male and 40% female patients and mean follow-up was six months. Time of union, deformity at fracture site, limb length discrepancy, knee range of motion and complications were assessed. Result Average age of the patients was 5.17 years (range 3 to 10). All patients achieved complete healing at a mean 12.8 weeks (range 10 to 20 weeks). Average limb length discrepancy was 0.16 cm (range -1.0 to 1.1 cm) average knee range of motion was 137.55 degrees (range 118 to 152 degrees). Complications were recorded in 13 (31.7%) patients and included: Five malunion which did not show any deformity or functional impairment and eight superficial wound infections which were healed after removal of nail. All patients were active as their pre injury levels at six months follow up. Conclusion Elastic stable intramedullary nailing is the method of choice for the simple pediatrics fracture shaft of femur, as it is minimally invasive and shows good functional and cosmetic results. It allows short hospital stay and quick recovery from pain and is cast-free. PMID- 27180363 TI - Association between Dental Prosthesis and Periodontal Disease among Patients Visiting a Tertiary Dental Care Centre in Eastern Nepal. AB - Background Dental caries and Periodontal diseases are the most prevalent oral health problems present globally. The distribution and severity of such oral health problems varies in different parts of the world and even in different regions of the same country. Nepal is one of the country with higher prevalence rate of these problems. These problems arise in association with multiple factors. Objective This study was carried out to describe the periodontal status and to analyse the association of periodontal disease with the wearing of fixed or removable partial dentures in a Nepalese population reporting to the College of Dental Surgery, B P Koirala Institute of Health Sciences, Dharan, Nepal. Method This study comprised of a sample of 200 adult individuals. All data were collected by performing clinical examinations in accordance with the World Health Organization Oral Health Surveys Basic Methods Criteria. It included the Community Periodontal Index and dental prosthesis examination. Result A descriptive analysis was performed and odds ratio (1.048) and 95% confidence interval (1.001; 1.096) was found out. The mean age of the population participated in the study was 41.82 +/- 14.80 years. A total of 93 (46.5%) males and 107 (53.5%) females participated in the study. Among these subjects, 100% presented some periodontal problems. The statistical analysis indicated that the probability of periodontal disease with regards to wearing partial dentures was not significant as suggested by the odds ratio (1.048). Conclusion There is no association of the wearing of dental prosthesis (RPD and/or FPD) with the periodontal disease and suggests a need for populations based oral health education programs, plaque control programs to reduce the incidence of periodontal disease. PMID- 27180364 TI - "Question of the Day": Impact on learning and retention. AB - Background Studying regularly has been a known method for better memory and long term retention of a subject. Getting students to study on a regular basis has been tried in many ways and its impact is increased if they understand the importance and value the efficiency of it. Objectives With large number of students, it would be a time consuming process to follow one on one interactions or study sessions. Hence, we introduced a new strategy, the "Question of the Day", which is interesting, challenging and most of all; it has produced positive influence on the examination performance of the students who performed this task. Main objective of this study was to make students answer questions related to the topics taught every day. Method Regular studying and updating the subject knowledge was provided through Question of the Day (Annexure-1). The students were given the questions on a regular basis during dissection classes and were asked to document the answers for those questions. Result The students who worked on the "Question of the Day" scored significantly higher in the exams than those who did not. The results of the opinion survey clearly indicated that this exercise was liked by most of the students. Conclusion "Question of the day" did have a positive influence on the student's performance. Most of the students felt that this exercise had a positive impact on their study methods, interaction with peers and teachers, retention and recollection of the knowledge. PMID- 27180365 TI - Efficacy of Different Antihypertensive Drugs among newly Diagnosed Hypertensive Patient in Dhulikhel Hospital. AB - Background Cardiovascular disease represents the largest burden on global health, important modifiable risk factor being hypertension. Difference in response to antihypertensive medication depending on ethnic group is well recognized. There is very few data regarding this difference in the South Asian population especially from Nepal. Objective The aim of this study is to find out which antihypertensive medication has better efficacy in our population. Method One seventy two newly diagnosed hypertensive patients who presented to cardiology OPD were included. Blood Pressure (BP) was recorded in both arms at least three times. Patients were counseled for lifestyle and dietary modification and were prescribed one of the three drugs Hydrochlorthiazide 25 mg or Amlodipine 5 mg or Enalapril 5 mg. Patients were called back in 4-6 weeks time and Blood Pressure was recorded in similar manner. Result Out of 172 patients, 97 were male and 75 female. The mean age was 55.49+/-1.03 years. Mean Systolic BP before treatment was 156.2+/-10.6 mm of Hg and Mean Diastolic BP before treatment was 100.5 +/-6.8 with no statistically significant difference among different groups. However Systolic BP reduction was 14.6 +/-5.1, 21.9+/-5.9 and 21.8+/-7.4 by Hydrochlorthiazide , Amlodipine and Enalapril respectively. Diastolic BP reduction was 8.8+/-2.5, 14.2+/-2.8 and 14.3+/-2.9 by Hydrochlorthiazide, Amlodipine and Enalapril respectively. Conclusion Amlodipine and Enalapril are equally effective in controlling BP in our population. Hydrochlorthiazide is less effective than both Amlodipine and Enalapril. PMID- 27180366 TI - Correlation between Endoscopic and Histopathological Findings in Gastric Lesions. AB - Background Stomach is a common site for wide variety of lesions. The visualisation of the site with biopsy leads to the early detection of the pathologic process and appropriate therapy. Objectives The objective of this study is to correlate the histopathological pattern of endoscopic biopsies with distribution of gastric lesions according to age and sex. Method The retrospective study was carried out among 50 cases with endoscopic biopsies and histopathological assessment, received at Department of Pathology, Dhulikhel Hospital- Kathmandu University Hospital. Result Out of 50 cases majority of cases were of male gender with male: female ratio was 1.3:1. Our study showed a poor correlation between endoscopic and histopathological evidence of inflammation in the stomach. Two cases were diagnosed as intestinal metaplasia which were diagnosed as ulcer and erosion endoscopically. Out of 32% of cases diagnosed endoscopically as ulcer, only one case was confirmed histopathologically. Our study showed good correlation in the cases of carcinoma. Out of 17 cases diagnosed endoscopically as gastric carcinoma correlated histopathologically as gastric adenocarcinoma. Majority of carcinoma cases showed ulcerating fungating growth followed by ulcero-proliferative growth. Conclusion Endoscopy is incomplete without biopsy and histopathology is the gold standard for the diagnosis of endoscopically detected lesions. Endoscopic examination and histopathological examination of suspected gastric lesions should go parallel and neither should be a substitute of each other. PMID- 27180367 TI - Relation between Serum Intact Parathyroid Hormone Level and Hematocrit in Chronic Kidney Disease Patients. AB - Background Anemia is a common complication of chronic kidney disease. There are various causes of anemia in chronic kidney disease patients on hemodialysis. Secondary hyperparathyroidism is one of the less recognized causes of anemia in chronic kidney disease patients. Objectives The main objective of the study is to find the correlation between intact parathyroid hormone and hematocrit level in chronic kidney disease (CKD) patients undergoing hemodialysis. Method Verbal consent was taken from all the participants. Eighty participants between the age of 29 and 70 years with chronic kidney disease having indication of hemodialysis were included in this study. Hematocrit was measured by bioelectrical impedance method and serum intact parathyroid hormone was by using Chemi Luminescence Immuno Assay (CLIA) method. Result A weak reverse correlation was found between serum intact parathyroid level and hematocrit (r= -0.33). Conclusion In chronic kidney disease patient, there is reverse correlation between level of serum intact parathyroid and hematocrit level. This association may have clinical relevance in assessing the cause of unexplained low hemoglobin level in CKD patients. PMID- 27180368 TI - Anthropometrically Determined Undernutrition among the Adolescent Girls in Kathmandu Valley. AB - Background No information exists regarding the health of the adolescent girls residing in Kathmandu valley in urban setup. Objective To evaluate the prevalence of undernutrition among the adolescent girls living in Kathmandu valley. It also aims to know the distribution of weight, height and body mass index of adolescent girls in relation to the different adolescent age groups. Method A cross sectional study was conducted in one government and two private schools in Kathmandu valley from 16th April to 15th September 2010. Anthropometric measurements were recorded using standardized methodology as recommended by World Health Organization (WHO). Standard operational definitions like percentiles, mean, standard deviation and proportions were used for analysis. Result Four hundred adolescent girls were enrolled randomly, out of which 111 girls (27.8%) were from government school and 289 girls (72.2 %) were from private schools. Maximum were of 16 years of age and the least were of 19 years of age, mean age being 15.4 years of age. Of them, early, mid and late adolescents were 41%, 35% and 24% respectively. Around one third of the study population were stunted (32%), one fourth were underweight (24%) and one tenth of them were thin (9.5%) based on National Center for Health Statistics (NCHS )standard. Both underweight and stunted girls were significantly more during the late adolescence period (P<0.001). However, thinness was not significant in any of the three adolescent age groups. Conclusion A high prevalence of undernutrition in terms of stunting, underweight and thinness exists among the adolescent girls in Kathmandu valley. PMID- 27180369 TI - Knowledge and Practice of Health Care Workers regarding Needle Stick Injuries in a Tertiary Care Center of Nepal. AB - Background Needle stick injuries are common health hazards among health care workers. Considering the increasing prevalence of body fluid borne infectious diseases; knowledge regarding the common errors and universal precautions are vital for the prevention of such accidents. Objective This study aimed to assess for knowledge and practice approaches among health care workers regarding needle stick injuries. Method This is a cross sectional survey was conducted using an anonymous, self-reporting 25-item structured questionnaire at a tertiary care center of central Nepal. A total of 165 health care personnel of working experience of more than 6 months were included in the study. Questionnaire included aspects of prevalence and knowledge on needle stick injury, hepatitis B immunization status and post exposure prophylaxis for HIV. Result Prevalence of needle stick injury was found to be 703 per 1000 health care worker (70.3%) during their working tenure and majority of the injury happened among nurses (p<0.05) besides other professions. Seventy nine (47.9%) participants experienced the injury more than one time in their career and the mean number of injury was 2.06+/-1.16. The practice of needle recapping is still prevalent and 80% participants often use single handed technique. Vaccination against hepatitis B virus was not completed by 31% health workers. Inadequate knowledge about post exposure prophylaxis for HIV was reported by 46% participants. Conclusion High prevalence of needle stick injury with a high rate of ignorance was noted. These issues need to be addressed, through appropriate education and interventional strategies. PMID- 27180371 TI - Factors Associated with Musculoskeletal Disorders among Registered Nurses: Evidence from the Thai Nurse Cohort Study. AB - Background Health, safety, and well being have been known to be influenced by occupational characteristics. Nurses constantly encounter musculoskeletal disorders (MSDs) from work demands worldwide. Nevertheless, there is insufficient of knowledge regarding causes of musculoskeletal disorders among nurses in Thailand. Objective To investigate factors associated with musculoskeletal disorder among registered nurses in Thailand. Method This study is part of the 2009 Thai Nurse Cohort Study which consisted of 18,756 nationally representative sample of registered nurses. Data collection was performed via postal self administered questionnaires. Manifesting musculoskeletal disorders was self reported by registered nurses, 1,070 nurses were excluded since they were unemployed during previous 12 months. Multiple logistic regression was used for data analysis. Result Of 17,686 registered nurses, the overall 12 months prevalence of musculoskeletal disorders was 47.8%. It was found that workplace violence was the strongest factor which statistically significant associated with musculoskeletal disorders (adjusted odds ratio, OR, 2.01; 95% confidence interval, 95% CI, 1.42 to 2.83; P < 0.001), anxiety/depression (OR = 1.96: 95% CI: 1.78 to 2.15; P < 0.001), perceiving job required a lot of physical effort (OR = 1.69; 95% CI: 1.52 to 1.87; P < 0.001), every 10 years increased of age (OR = 1.40; 95% CI: 1.22 to 1.62; P < 0.001), overweight (OR = 1.39; 95% CI: 1.01 to 1.52; P = 0.015). Conclusion Registered nurses were most vulnerable of musculoskeletal disorders especially those who experienced workplace violence, anxiety/depression, strenuous work, older age, and overweight. Consequently, recommending safety practices to nurses should be considered for musculoskeletal disorders (MSDs) prevention by ergonomics and workplace design. PMID- 27180370 TI - Short Term Fate of Great Saphenous Vein after Radiofrequency Ablation for Varicose Veins. AB - Background Radiofrequency ablation of varicose vein have gained popularity compared to conventional surgery due to comparable long term results in addition to definite immediate superiorities. This modality has been started in Nepal since August 2003 and the study on short term fate of ablated vein segment confirms the anatomical benefit in addition to the clinical benefit. Objective To analyze short term fate of segment of great saphenous vein that has been treated by Radiofrequency ablation in terms of occlusion of saphenofemoral junction and absence of recanalisation on Doppler ultrasonography finding done at 3-6 months postoperative period. Method Total 81 cases subjected for radiofrequency ablation of great saphenous vein in thigh segment during August 2013 - September 2014 were followed up in between 3 to 6 months by Doppler ultrasonography. The findings were classified into type 1 to 4 results based on the anatomic closure of saphenofemoral junction and absence of recanalisation on treated segments. Result There were total 81 cases with 54.3% female and 45.7% male patients. Mean short term follow up duration was 4.9 months (S.D. 1.1 months). Great Saphenous Vein was cannulated most frequently in between 5 cm above knee to 5 cm below knee. Mean number of Radio Frequency Ablation (RFA) segments were 6.6 (SD=3.1). There was complete occlusion (Type 1 results) in 51 cases (63.0%). In 24 cases (29.6%) there was competent saphenofemoral junction with partial recanalisation in distal part of Great Saphenous Vein (GSV) (Type 2 results). In six cases (7.4%) there was incompetent saphenofemoral junction with partial recanalisation in distal part of Great Saphenous Vein (Type 3 results). There were no cases with incompetent saphenofemoral junction with complete recanalisation in distal part of Great Saphenous Vein (Type 4 results). Conclusion Radio Frequency Ablation for varicose vein, besides making clinical improvements, is also associated with good anatomical results. PMID- 27180372 TI - Nepalese Esthetic Dental (NED) Proportion in Nepalese Population. AB - Background Lots of studies on maxillary anterior teeth proportions have been studied in different populations in various countries, but no studies have been conducted in Nepal on the esthetic maxillary anterior teeth proportions. Objective The study was done to investigate the maxillary anterior teeth proportions in a Nepalese population. Teeth proportions in the total population were compared with golden proportion (GP) and golden standard (GS). Method A total of 150 Nepalese subjects were divided in three facial types; broad, average and narrow group. Maxillary anterior teeth were measured from dental casts using digital calipers. The perceived width ratios of lateral to central incisor (LI/CI) and canine to lateral incisor (CN/LI), ratios of mean central incisor length to 2 central incisor widths (CIL/2CIW), and actual width to length ratios (WLRs) (%) were calculated in each facial type and compared. Mean LI/CI, CN/LI and CIL/2CIW in total population were calculated and compared with GP (0.618), and mean WLRs in the total population were compared with GS (80%). All teeth proportions were compared among three facial types. One-sample t-test and one-way ANOVA were performed to analyze the data (alpha = 0.05). Result The LI/CI, CN/LI, CIL/2CIW and WLRs in three facial types showed no significant difference. The LI/CI, CN/LI and CIL/2CIW in the total population were 66%, 70% and 55% respectively, and were significantly different from GP. The WLRs for CI, LI and CN in the total population were 90%, 86% and 89% respectively and significantly differed from GS. These values were considered to constitute the Nepalese Esthetic Dental (NED) proportion. Conclusion No significant difference of maxillary anterior teeth proportions were observed among three facial types. Teeth proportions in the total population significantly differed from GP and GS. We propose the NED proportion as a guideline for dental treatment in the maxillary anterior region in Nepalese populations. PMID- 27180373 TI - Study of Pre-disposing Factors of Acute Exacerbation of Chronic Obstructive Pulmonary Disease and Antibiotic Prescribing Pattern with Reference to Antibiotic Sensitivity Test. AB - Background Chronic Obstructive Pulmonary Disease (COPD) affects about 329 million people worldwide, which is nearly 5% of the entire global population. In the context of Nepal, COPD accounts for 43% of the non-communicable disease burden and 2.56% of hospitalizations. Various pre-disposing factors like bacterial, viral, fungal, smoking, occupational exposures and genetic factors have been proposed to precipitate COPD and its exacerbation though, the definitive pre disposing factors and factors related to acute exacerbation have not been determined in the context of Nepal. Objective To find out the pre-disposing factors and the related causative agents for COPD. Method A cross sectional study was conducted in a tertiary care hospital. Patients of all age group who were diagnosed as COPD and admitted in the hospital were included in this study. Patients were interviewed using structured questionnaire. The sociodemographic data including personal and medical history were recorded from those participants. In addition, sputum from those patients was sent for culture to investigate the possible responsible pathogens as well as its antibiotic sensitivity pattern. Result A total of 150 patients having Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD) who have admitted from either emergency or out-patient department of the hospital were included in this study. Among the total number of patients, more than half of them were female (n=82). In addition, analysis of occupations shows that most of them were either farmer (36.0%) or housewife (30.7%). In total studied patients (n=150), most of them were using traditional firewood (83%) for cooking purpose and majority of patients (91%) were smokers. Most of the sputum samples show growth of gram positive cocci (26.7%) and gram negative bacilli (27.5%). Considering the overall sensitivity pattern, the higher sensitivity was recorded for Co-trimoxazole and Ciprofloxacin while higher rate of resistance was noted for Penicillin group of drugs. The most widely used antibiotics were found to be Cephalosporin group of drugs (68%). Conclusion The present study revealed that the case of COPD is more in female and the commonest pre-disposing factor is found to be smoke/firewood. Cephalosporin group of drugs is the most commonly prescribed drug. PMID- 27180374 TI - Fluoroscopy Guided Percutaneous Transpedicular Biopsy for Thoracic and Lumbar Vertebral Body Lesion: Technique and Safety in 23 Consecutive Cases. AB - Background Though some vertebral lesions have typical imaging findings, histological/ microbiological evidence are required for definitive diagnosis and management, specially for tumor and infective lesions so that wrong diagnosis and wrong treatment can be avoided. Conventionally, open biopsy methods are used. With availability of CT scan, MRI, percutaneous transpedicular vertebral biopsy has now become popular as a minimally invasive technique for biopsy of vertebral lesion. Objective To describes technique and to analyzes safety and feasibility of percutaneous transpedicular vertebral biopsy with fluoroscopy guidance for thoracic and lumbar vertebral body lesions. Method Twenty three patients who underwent percutaneous transpedicular vertebral biopsy under fluoroscopy guidance were retrospectively evaluated for demographic data, indication for biopsy, anatomical locations, histological/microbiological diagnosis, complications and final outcome of treatment. True positive, true negative, false positive and false negative cases were defined. Result There were 17 males and 6 female patients of mean age 47 (range 22-73 years). Biopsies were performed in 17 dorsal and six lumbar vertebral bodies. Adequate sample were obtained in all cases. Seventeen patients (12: tubercular pathology, 1: primary tumor, 3: metastasis, 1: osteoporotic fracture) had definitive histological/ microbiological diagnosis. Four patients had no granuloma and tumor. Two had histological features of chronic non specific inflammation. True positive cases were 17, true negative were four and false negative case were two. Overall accuracy was 92%. One patient developed small hematoma at biopsy site. Conclusion Fluoroscopy guided percutaneous transpedicular biopsy of is a safe procedure with high adequacy and accuracy and low complication rate for thoracic and lumbar vertebral body lesion. PMID- 27180375 TI - Study on Corticosteroids use Pattern in Dermatological Practice and Investigating Adverse Effect of Corticosteroids Including its Associated Factors. AB - Background Corticosteroids are highly effective drugs with anti-inflammatory and immunosuppressive properties. Due to this, they have become a mainstay of pharmacotherapy in dermatology. However, improper and long term uses are associated with a number of serious adverse effects. Objective To investigate the corticosteroids use pattern, adverse effects and various factors associated with adverse effects in dermatological practice. Method A cross-sectional study was conducted in a dermatology department of tertiary care hospital. All patients using at least one corticosteroids, either topically or systemically or the combination were included in this study. Informed consent was taken from the patients and interviewed using structured questionnaire. Statistical analysis was performed by using SPSS 20. p-value < 0.05 was considered as statistically significant. Result Among the 60 participants under this study, 81.67% of them were females. The mean (+/-SD) age of the patients was 31.03 years (+/-15.0). A majority (58.30%) of the patients was prescribed with topical corticosteroids with low potency (25%). Most of them had used corticosteroids for urticaria. Adverse effects were reported by 33.30% of the patients. The most common adverse effect reported was the shedding of skin. Adverse effects was significantly associated with gender; use of systemic corticosteroids; regular use of corticosteroids; discontinuation of dose abruptly; and missed dose. However, there was no significant association between adverse effects and the duration of use of corticosteroids. Conclusion In conclusion, the present study suggested that the proper counselling and clear instruction regarding the use of corticosteroid should be provided to the patients for avoiding the abrupt discontinuation of the prescribed medication leading to treatment failure. PMID- 27180376 TI - Uterine Tachysystole with Prolonged Deceleration Following Nipple Stimulation for Labor Augmentation. AB - Breast stimulation for inducing uterine contractions has been reported in the medical literature since the 18th century. The American college of Obstetricians and Gynecologists (ACOG) has described nipple stimulation as a natural and inexpensive nonmedical method for inducing labor. We report on a 37 year old P2 with a singleton pregnancy at 40 weeks gestation who developed tachysystole with a prolonged deceleration after nipple stimulation for augmentation of labor. Initial resuscitative measures, including oxygen by mask, a bolus of intravenous fluids and left lateral positioning, did not restore the fetal heart rate to normal. After the administration of Terbutaline 250 mcg subcutaneously, the tachysystole resolved and the fetal heart rate recovered after five minutes of bradycardia. Most trials of nipple stimulation for induction or augmentation of labor have had small study populations, and no conclusions could be drawn about the safety of nipple stimulation, though its use is widespread. While there have been a few reports of similar complications during nipple stimulation for contraction stress testing, there are no previous reports of tachysystole with sustained bradycardia following nipple stimulation for labor augmentation. In this report, we draw attention to the dangers of nipple stimulation so that providers will be aware of this potential complication. PMID- 27180377 TI - Sydenham's Chorea as Presentation of Rheumatic Heart Disease. AB - Sydenham's chorea is the most common type of acquired chorea in childhood which is a major neurological manifestation of rheumatic fever. We describe a 13 years old girl who presented with weakness and purposeless involuntary movements of upper and lower limbs. The symptoms slightly affected the child's daily activities and had an unstable gait on walking which was aggravated during stress. Grade II ejection systolic murmur was noticed on cardiovascular examination. Echocardiography evaluation showed thickened aortic and mitral valve leaflets with mild to moderate degree of mitral regurgitation. Anti-streptolysin O titer was positive (>=200 IU/ml). CT scan of brain was normal. Subsequently child was diagnosed as Rheumatic heart disease with Sydenham's chorea and kept on regular Benzathine penicillin prophylaxis. Symptoms subsided spontaneously after 3 months without any further complications. Although decreasing, early diagnosis and management of Sydenham's chorea and Rheumatic heart disease are very crucial and should be considered with such presentation. PMID- 27180378 TI - Significance of Crime Scene Visit by Forensic Pathologist in Cases of Atypical Firearm Injuries. AB - Deaths due to firearms are some of the interesting and contentious cases that a forensic pathologist/autopsy surgeon encounters in his practice. Whenever there is 'ambiguity' regarding the nature or sequence of events any unnatural deaths including those caused by firearms the practice of visiting crime scene should be encouraged especially in a country like India where autopsy surgeons often neglect it. Here we present a case report in which there were inconsistencies in the autopsy findings with the alleged history. The witnesses heard about four to six gunshot sounds, whereas only two spent cartridge cases were retrieved from the crime scene. Authors identified the atypical nature of firearm injuries sustained by the victims that were possible by just two bullets. Crime scene visit was undertaken where we discovered the possibility of the echo effect behind the production of four to six sounds. Further by using computer software program, positions of the gunman, victims and the bullet trajectory of the two bullets was created. PMID- 27180379 TI - History of Nutrition: The Long Road Leading to the Dietary Reference Intakes for the United States and Canada. AB - The Dietary Reference Intakes (DRIs) are reference values to guide the planning and assessing of nutrient intakes in the United States and Canada. The DRI framework was conceptualized in 1994, and the first reports were issued from 1997 2004, based on work by expert panels and subcommittees under the guidance of the Food and Nutrition Board of the Institute of Medicine. Numerous conventions, challenges, and controversies were encountered during the process of defining and setting the DRIs, including the definition of the framework, the use of chronic disease endpoints, lack of data on requirements for children and youth, and methods for addressing nonessential bioactive substances with potential health benefits. DRIs may be used to plan and assess the nutrient intakes of both individuals and population groups, but the new paradigm particularly improved methods used for groups. It is now possible to estimate both the prevalence of inadequate intake and the prevalence of potentially excessive intake within a group. The DRIs have served as a potent influence on national nutrition policies, including those related to dietary guidance, food labeling, nutrition monitoring, food assistance programs, and military nutrition standards. Because of this important impact on nutrition policy, the DRIs must be based on the best possible and most up-to-date science. Unfortunately, no updates to specific DRIs are currently planned. Despite the long and challenging road that led to the current DRIs, it must not finish in a dead end. Monetary resources and political will are crucial to maintaining and continuously updating the DRIs. PMID- 27180383 TI - Remembering John D. States, M.D. PMID- 27180382 TI - The eNutrition Academy: Supporting a New Generation of Nutritional Scientists around the World. AB - Nutrition training and building capacity to provide a competent workforce to support national and regional efforts to combat malnutrition remain a major challenge in Africa and other developing regions of the world. The capacity to provide the necessary intellectual drive for nutrition research, policy, and practice in countries lacking in readiness for nutrition actions is imperative to improve the health of their people. To help address this need, the eNutrition Academy (eNA) was formed as a global partnership organization by the African Nutrition Society, the Federation of African Nutrition Societies, the Nutrition Society of the United Kingdom and Ireland, the ASN, and the International Union of Nutritional Sciences, supported by Cambridge University Press. The primary objective of this partnership is to provide an online learning platform that is free to access, enabling users to benefit from a wide range of learning materials from basic tools to more-advanced learning materials for teachers and researchers in developing countries. The goal of this article was to summarize the findings of a symposium held at the ASN Scientific Sessions and Annual Meeting at Experimental Biology 2015, which explored the themes of international capacity development, with a particular focus on the African continent, online learning, and the eNA e-learning platform. Given the vast human capacity present in Africa that is poised to create new solutions to address the public health needs of the continent, now is an opportune time to establish South-North and South-South partnerships to develop the next generation of African nutritional scientists. PMID- 27180384 TI - Emerging Data on the State of Obesity. PMID- 27180380 TI - Role of the Small Intestine in Developmental Programming: Impact of Maternal Nutrition on the Dam and Offspring. AB - Small-intestinal growth and function are critical for optimal animal growth and health and play a major role in nutrient digestion and absorption, energy and nutrient expenditure, and immunological competence. During fetal and perinatal development, the small intestine is affected by the maternal environment and nutrient intake. In ruminants, altered small-intestinal mass, villi morphology, hypertrophy, hyperplasia, vascularity, and gene expression have been observed as a result of poor gestational nutrition or intrauterine growth restriction. Although many of these data come from fetal stages, data have also demonstrated that nutrition during mid- and late gestation affects lamb small-intestinal growth, vascularity, digestive enzyme activity, and gene expression at 20 and 180 d of age as well. The small intestine is known to be a highly plastic tissue, changing with nutrient intake and physiological state even in adulthood, and the maternal small intestine adapts to pregnancy and advancing gestation. In ruminants, the growth, vascularity, and gene expression of the maternal small intestine also adapt to the nutritional plane and specific nutrient intake such as high selenium during pregnancy. These changes likely alter both pre- and postnatal nutrient delivery to offspring. More research is necessary to better understand the role of the offspring and maternal small intestines in whole animal responses to developmental programming, but programming of this plastic tissue seems to play a dynamic role in gestational nutrition impacts on the whole animal. PMID- 27180381 TI - Holistic Analysis Enhances the Description of Metabolic Complexity in Dietary Natural Products. AB - In the field of food and nutrition, complex natural products (NPs) are typically obtained from cells/tissues of diverse organisms such as plants, mushrooms, and animals. Among them, edible fruits, grains, and vegetables represent most of the human diet. Because of an important dietary dependence, the comprehensive metabolomic analysis of dietary NPs, performed holistically via the assessment of as many metabolites as possible, constitutes a fundamental building block for understanding the human diet. Both mass spectrometry (MS) and nuclear magnetic resonance (NMR) are important complementary analytic techniques, covering a wide range of metabolites at different concentrations. Particularly, 1-dimensional 1H NMR offers an unbiased overview of all metabolites present in a sample without prior knowledge of its composition, thereby leading to an untargeted analysis. In the past decade, NMR-based metabolomics in plant and food analyses has evolved considerably. The scope of the present review, covering literature of the past 5 y, is to address the relevance of 1H-NMR-based metabolomics in food plant studies, including a comparison with MS-based techniques. Major applications of NMR-based metabolomics for the quality control of dietary NPs and assessment of their nutritional values are presented. PMID- 27180385 TI - [Back into the clinic - was that necessary?]. PMID- 27180386 TI - [General practitioners should not accept reduced fees for psychological codes]. PMID- 27180387 TI - [Not omitting the fee in prevention]. PMID- 27180388 TI - [Liquid formula nutrition by prescription?]. PMID- 27180389 TI - [Not Available]. PMID- 27180390 TI - [Not Available]. PMID- 27180391 TI - Highlighting Hospital and Patient Concerns this Election Year. AB - Campaign 2016 is in full swing, and the American Hospital Association is seizing the opportunity to make sure the concerns of patients and hospitals are heard. On the front burner: escalating drug prices. PMID- 27180392 TI - Duration of Nurse Residency Key. PMID- 27180393 TI - NEED A RIDE? Health system partners to provide reliable transportion for patients. PMID- 27180394 TI - HOOTENANNY. Singing away the blues, COPD. PMID- 27180395 TI - MORE THAN MEDICINE. Franchise business model helps build a continuum of care. PMID- 27180396 TI - INDEPENDENT & LOCAL. Three questions with: Michael Hansen. PMID- 27180398 TI - Cleaning out the closet. PMID- 27180397 TI - TEACHING COMPASSION. MDs want to know more about end-of-life counseling. PMID- 27180399 TI - The Opioid Epidemic. PMID- 27180400 TI - Q&A with Peter Holden. PMID- 27180401 TI - Designing a Medical School from Scratch. PMID- 27180402 TI - PHARMACISTS to the fore. PMID- 27180403 TI - Do You Really Know Your CUSTOMER? AB - Customer segmentation has long been used in the retail industry. Now hospitals are adapting it to better understand and care for patients. PMID- 27180404 TI - Certificate of Need: '70s Remnant Shows Its Age. PMID- 27180405 TI - Medicare Advantage's Influence Felt in Accountable Care Model. PMID- 27180406 TI - The New Health Insurance Ecosystem. PMID- 27180407 TI - AHIP Ship Sails Rough Seas. PMID- 27180408 TI - Selfie Health Insurance Is All the Rage. PMID- 27180409 TI - When Payers and Providers Become One. PMID- 27180410 TI - Some Health Insurance Plans Groan About Not Making It on Exchanges. PMID- 27180411 TI - Critical Illness Policies: An Antidote or a Band-Aid for Health Care's Financial Toxicity? PMID- 27180412 TI - Symptom Monitoring Improves Cancer Care. PMID- 27180413 TI - Fixing Utilization Management To Fit With a Value-Based World. PMID- 27180414 TI - SYSTEM CHANGE CREATES OPPORTUNITY FOR NEW PRIMARY CARE MODELS. PMID- 27180415 TI - Testing and Treating HCV in Arkansas. PMID- 27180416 TI - The State of Public Health in Arkansas in 2015. PMID- 27180417 TI - Preventing Substance Abuse With Data-Driven Coalitions. PMID- 27180418 TI - Report of the Trustee District Task Force. PMID- 27180419 TI - ELECTRON DONOR ACCEPTOR DESCRIPTORS OF THE SINGLE AND DOUBLE BONDED SUBSTITUENT AND HETEROATOM INCORPORATION EFFECTS. A REVIEW. AB - The properties of the series of Electron Donor-Acceptor (EDA) descriptors of classical substituent effect (sEDA(I), pEDA(I)), double bonded substituent effect (sEDA(=), pEDA(=)), heteroatom incorporation effect in monocyclic systems (sEDA(II), pEDA(II)), and in ring-junction position (sEDA(III), pEDA(III)), are reviewed. The descriptors show the amount of electrons donated to or withdrawn from the sigma-(sEDA) or pi(pEDA) valence orbitals by the substituent or incorporant. The new descriptors are expected to enrich the potency of QSAR analyses in drug design and materials chemistry. PMID- 27180421 TI - EFFECT OF MICROWAVE POWER ON SHAPE OF EPR SPECTRA--APPLICATION TO EXAMINATION OF COMPLEX FREE RADICAL SYSTEM IN THERMALLY STERILIZED ACIDUM BORICUM. AB - Complex free radical system in thermally sterilized acidum boricum (AB) was studied. Acidum boricum was sterilized at temperatures and times given by pharmaceutical norms: 160 degrees C and 120 min, 170 degrees C and 60 min and 180 degrees C and 30 min. The advanced spectroscopic tests were performed. The EPR spectra of free radicals were measured as the first derivatives with microwaves of 9.3 GHz frequency and magnetic modulation of 100 kHz. The Polish X-band electron paramagnetic resonance spectrometer of Radiopan (Poznan) was used. EPR lines were not observed for the nonheated AB. The broad EPR asymmetric lines were obtained for all the heated AB samples. The influence of microwave power in the range of 2.2-70 mW on the shape of EPR spectra of the heated drug samples was tested. The following asymmetry parameters: A1/A2, A1-A2, B1/B2, and B1-B2, were analyzed. The changes of these parameters with microwave power were observed. The strong dependence of shape and its parameters on microwave power proved the complex character of free radical system in thermally sterilized AB. Changes of microwave power during the detection of EPR spectra indicated complex character of free radicals in AB sterilized in hot air under all the tested conditions. Thermolysis, interactions between free radicals and interactions of free radicals with oxygen may be responsible for the complex free radicals system in thermally treated AB. Usefulness of continuous microwave saturation of EPR lines and shape analysis to examine free radicals in thermally sterilized drugs was confirmed. PMID- 27180420 TI - LEVOMILNACIPRAN--A SUCCESSOR OF MILNACIPRAN WITH A HIGHER NORADRENERGIC SELECTIVITY. AB - A new antidepressant, levomilnacipran, is the levorotatory enantiomer of milnacipran. The drug belongs to selective serotonin-norepinephrine reuptake inhibitors (SNRI) and has the highest noradrenergic selectivity of all members of this group of antidepressants. Clinical trials have confirmed the effectiveness of levomilnacipran in the treatment of depression. The drug was placed on the US market in the form of prolonged-release capsules, which greatly simplifies the treatment of psychiatric patients. The safety of the drug is also higher than the safety of a racemate, resulting in a beneficial impact on the therapeutic effect. In this paper we present current information on the pharmacological and clinical properties of the newest antidepressant--levomilnacipran. PMID- 27180422 TI - UNUSUALLY STABLE ADDUCT BETWEEN METHANOLYZED AMOXICILLIN OR AMPICILLIN AND THEIR DIKETOPIPERAZINE DERIVATIVES. AB - Amoxicillin and ampicillin were subjected to methanolysis. As expected, the methanolysis products were observed by HPLC-ESI-MS. Besides these products, diketopiperazine derivatives were also detected. Additionally, unusually stable adduct formed between the products of methanolysis and diketopiperazine derivatives was also identified. Analogical adducts were detected when ethanolysis was performed instead of methanolysis. HPLC-ESI-MS analysis of the separated adducts confirmed that the adducts were composed of methanolysis products and diketopiperazine derivatives. PMID- 27180423 TI - CREATININE DETERMINATION IN URINE BY LIQUID CHROMATOGRAPHY-ELECTROSPRAY IONIZATION-TANDEM MASS SPECTROMETRY METHOD. AB - Creatinine determination in urine is used to estimate the completeness of the 24 h urine collection, compensation for variable diuresis and as a preliminary step in protein profiling in urine. Despite the fact that a wide range of methods of measuring creatinine level in biofluids has been developed, many of them are adversely affected by interfering substances. A new liquid chromatography-tandem mass spectrometry method for creatinine determination in urine has been developed. Chromatographic separation was performed by applying C18 column and a gradient elution. Analyses were carried out on a triple quadrupole mass spectrometer equipped with an electrospray ion source. The developed method was fully validated according to the international guidelines. The quantification range of the method was 5-1500 ng/mL, which corresponds to 1-300 mg/dL in urine. Limit of detection and quantitation were 2 and 5 ng/mL, respectively. Additionally, the comparison of creatinine determination by newly developed method to the colorimetric method was performed. The method enables the determination of creatinine in urine samples with a minimal sample preparation, excellent sensitivity and prominent selectivity. Since mass spectrometry allows to measure a number of compounds simultaneously, a future perspective would be to incorporate the determination of other clinically important compounds excreted in urine. PMID- 27180424 TI - CONJUGATED LINOLEIC ACIDS (CLA) DECREASE THE BREAST CANCER RISK IN DMBA-TREATED RATS. AB - The aim of this study was to investigate how supplementation of diet of female Sprague-Dawley rats with different doses of conjugated linoleic acids and for a varied period of time influences breast cancer risk, fatty acids profile and lipids peroxidation in chemically induced mammary tumors. Animals were divided into nine groups with different modifications of diet (vegetable oil, 1.0 or 2.0% of CLA) and period of supplementation, which lasted after (A), before (B) and before and after (BA) carcinogenic agent--7,12-dimethylbenz[a]anthracene administration at 50th day of life. Mammary adenocarcinomas occurred in all groups, but CLA supplementation decreased the cancer morbidity. Two percent CLA seems to be excessive because of the coexisting cachexia. Two CLA isomers (9-cis, 11-trans and 10-trans, 12-cis) were detected in tumors but content of rumenic acid was higher. Dietary supplementation significantly influenced some unsaturated fatty acids content (C18:2 n-6 trans, C20:1, C20:5 n-3, C22:2), but the anti- or prooxidant properties of CLA were not confirmed. CLA can inhibit chemically induced mammary tumors development in female rats, but their cytotoxic action seems not to be connected with lipids peroxidation. CLA isomers differ with their incorporation into cancerous tissues and they influence the content of some other fatty acids. PMID- 27180425 TI - NEW RENIN-INHIBITORS--STABILITY AND ACTIVITY DETERMINATION. PART III. AB - A series of new four potential renin inhibitors containing pseudodipeptides were synthesized. Stability for all compounds (1-4) in homogenates of liver, kidney, lung and in serum, gastric, intestinal juice and in the presence of alpha chymotrypsin was determined. Compound 1 was unstable, compounds 2, 3 were stable, compound 4 was partly unstable, (liver and kidney homogenates, (alpha chymotrypsin solution). Inhibitory activity of the compounds was measured in vitro by HPLC determination of lowering concentration of substrate (angiotensinogen) in the presence of renin and the potential renin inhibitor (compounds 1-4). Compound 1, 2, 3 and 4 showed inhibitory activity (1.7 x 10(-6), 9.6 x 10(-7), 1.05 x 10(-9) and 1.31 x 10(-7)M, respectively). PMID- 27180426 TI - SERUM ANTIOXIDANT PARAMETERS IN PATIENTS POISONED BY DIFFERENT XENOBIOTICS. AB - There is a great diversity of the acute drugs overdose cases in clinical toxicology. Clinical situation is complicated by the coexistence of factors predisposing to the development of adverse drug reactions (chronic use of drugs, polypharmacy, alcohol or drugs dependence, nutritional disorders) and by the presence of chronic organ damage, especially the liver and the kidney. The aim of this study was to evaluate whether there are sensitive plasma markers belonging to the antioxidant system in patients exposed to various xenobiotics. We measured the activity of antioxidant parameters: catalase (CAT), glutathione peroxidase (GPX3), glutathione (GSH), sulfhydryl groups (-SH), carbonyl groups (=CO) and free radicals (2,2-diphenyl-1-picrylhydrazyl, DPPH, assay) in serum of 49 patients with acute intoxication caused by carbamazepine (CBZ, n = 9), mixed drug intoxication (MDI) (n = 9), alcohol withdrawal syndrome (AWS, n = 9), acetaminophen (APAP, n = 7), tricyclic antidepressants (TCAs) (n = 5), valproic acids (VA, n = 4), narcotics (N, n = 3), and three others (benzodiazepines, BZD, n = 2; barbiturates, n = 1). The results were compared with the parameters of not intoxicated patients (n = 39). All patients had lower catalase activity in comparison to the control group (41.9 +/- 16.5 vs. 196.0 +/- 82.2 U/mg protein, p = 0.000), while the increase of GSH level was particularly apparent only in patients with AWS (391.3 +/- 257.9 MUmol/mg protein) compared to the control group (171.4 +/- 88.4 MUmol/mg protein, p = 0.034) and to patients intoxicated with carbamazepine (152.8 +/- 102.5 MUmol/mg protein, p = 0.027). Some differences, but without statistical significance, were also observed in GPX3 activity between different groups of poisoned patients. PMID- 27180428 TI - DESIGN, SYNTHESIS AND BIOLOGICAL EVALUATION OF NEW PYRROLOAZEPINES WITH POTENTIAL AND SELECTIVE ANTITUMOR ACTIVITY. AB - 2-Chloroacetylamino-pyrrolo[1,2-a]azepine-3-ethyl ester 3 was synthesized, condensed with ammonium thiocyanate to obtain a hybrid molecule of pyrrolo [1,2 a]azepine and thiazolidinone moiety 4. Coupling of the obtained hybrid molecule with the appropriate aldehydes or diazonium salt afforded novel substituted hybrids 5a,b and 6. Chemical structures were confirmed by spectral and elemental analysis. The synthesized compounds were tested on liver Hep3B, lung A549, breast MCF7 cancer cell lines and normal fibroblast cells as well, using sulforhodamine B assay method. Compound 5a showed to be potent and selective to lung A549 cancer cell line (IC50 = 13 nM/mL, S.I. = 2.9). The most potent one against MCF7 was compound 4 with IC50 value equals 12 nM/mL and S.I. = 1.4. Compounds 5b, 6 exhibited high potency and selectivity towards Hep3B cancer cells with IC50 and S.I. equal 15 nM/mL, 10.8 and 9 nM/mL, 285, respectively. The ability of the synthesized compounds 3-6 to act as modulators for cyclin dependent kinases was explored through molecular docking studies. PMID- 27180427 TI - PRELIMINARY EVALUATION OF CENTRAL NERVOUS SYSTEM ACTIVITY OF (E)-N-2-METHYL-3 PHENYLPROP-2-ENYL ((E)-N- alpha-METHYLCINNAMYL) DERIVATIVES OF SELECTED AMINOALKANOLS. AB - A series of (E)-alpha-methylcinnamyl derivatives of selected aminoalkanols was synthetized and evaluated for activity in central nervous system. All compounds were tested as anticonvulsants and one additionally in antidepressant- and anxiolytic-like assays. The compounds possessed pharmacophoric elements regarded as beneficial for anticonvulsant activity: hydrophobic unit and two hydrogen bonds donor/acceptor features. The compounds were verified in mice after intraperitoneal (i.p.) administration in maximal electroshock (MES) and subcutaneous pentetrazole (scPTZ) induced seizures as well as neurotoxicity assessments. Eight of the tested substances showed protection in MES test at the dose of 100 mg/kg. The derivative of 2-aminopropan-1-ol was also tested in 6-Hz test in mice i.p. and showed anticonvulsant activity but at the same time the neurotoxicity was noted. The derivative of 2-amino-1-phenylethanol which possessed additional hydrophobic unit in aminoalkanol moiety was tested in other in vivo assays to evaluate antidepressant- and anxiolytic-like activity. The compound proved beneficial properties especially as anxiolytic agent remaining active in four-plate test in mice at the dose of 2.5 mg/kg (i.p.). In vitro biotransformation studies of 2-amino-1-phenylethanol derivative carried out in mouse liver microsomal assay indicated two main metabolites as a result of aliphatic and aromatic hydroxylation or aliphatic carbonylation. To identify possible mechanism of action, we evaluated serotonin receptors (5-HT1A, 5-HT6 and 5-HT7) binding affinities of the compounds but none of them proved to bind to any of tested receptors. PMID- 27180429 TI - RECEPTOR AFFINITY AND PHOSPHODIESTERASES 4B AND 10A ACTIVITY OF OCTAHYDRO- AND 6,7-DIMETHOXY-3,4-DIHYDRO- ISOQUINOLIN-2(1H)-YL-ALKYL DERIVATIVES OF IMIDAZO- AND PYRIMIDINO[2,1-f]PURINES. AB - A series of octahydro- and 6,7-dimethoxy-3,4-dihydro- isoquinolin-2(1H)-yl-alkyl derivatives of imidazo- and pyrimidino[2,1-f]purines were synthesized and biologically evaluated in in vitro competition binding experiments for serotonin 5-HT(1A), 5-HT(6), 5-HT(7), and dopamine D2 receptors and inhibitory potencies for phosphodiesterases - PDE4B1 and PDE10A. The structure-activity relationships allowed to determine the structural features responsible for receptor and enzyme activity. Compound 5 (8-(4-(6,7-dimethoxy-3,4-dihydroiso- quinolin-2(1H)butyl)1,3 dimethyl-H-imidazo[2,1-f]purine-2,4(3H,8H)-dione) could be regarded as promising structure for further modification and detailed mechanistic study for obtained hybrid ligands. PMID- 27180430 TI - ANTIRADICAL AND ANTIMICROBIAL ACTIVITY OF PHENOLIC FRACTIONS OBTAINED FROM HONEYS. AB - Honey is a natural product consisting of multiple components which determine its dietary and medicinal properties. In this work there were studied methanol fractions obtained from seven honeys from Lower Silesia (Poland) collected in different seasons of three successive years. Melissopalynologic studies revealed that two of them were polyfloral, and five were classified as monofloral (two buckwheat and three rapes). The amount of phenolic compounds in honeys varied from 0.09 to 0.38 mg per g of honey. Honeys harvested in 2010 were the richest in phenolic compounds and especially rich was buckwheat honey, comparing to 2011- 2012. Determination of antioxidant potential with the DPPH radical revealed that the strongest antiradical activity was exhibited by extracts obtained from polyfloral (1.22 TAU(515/mg)) and buckwheat (1.06 TAU(515lmg)) honeys, while the highest number of antiradical units was observed for rape honey (3.64 TAU(515/g)). Polyphenolic fractions exhibited various bactericidal activities against Klebsiella pneumoniae and Staphylococcus aureus and weak or no activity was observed against Pseudomonas aeruginosa. PMID- 27180431 TI - EVALUATION OF THE TEA TREE OIL ACTIVITY TO ANAEROBIC BACTERIA--IN VITRO STUDY. AB - The study of the sensitivity to tea tree oil (Australian Company TTD International Pty. Ltd. Sydney) was carried out on 193 strains of anaerobic bacteria isolated from patients with various infections within the oral cavity and respiratory tracts. The susceptibility (MIC) of anaerobes was determined by means of plate dilution technique in Brucella agar supplemented with 5% defibrinated sheep blood, menadione and hemin. Inoculum contained 10(5) CFU per spot was cultured with Steers replicator upon the surface of agar with various tea tree oil concentrations or without oil (anaerobes growth control). Incubation the plates was performed in anaerobic jars under anaerobic conditions at 37 degrees C for 48 h. MIC was defined as the lowest concentrations of the essential oil completely inhibiting growth of anaerobic bacteria. Test results indicate, that among Gram-negative bacteria the most sensitive to essential oil were strains of Veillonella and Porphyromonas species. Essential oil in low concentrations (MIC in the range of = 0.12 - 0.5 mg/mL) inhibited growth of accordingly 80% and 68% strains. The least sensitive were strains of the genus Tannerella, Parabacteroides and Dialister (MIC 1.0 - 2.0 mg/mL). In the case of Gram-positive anaerobic bacteria the tea tree oil was the most active to strains of cocci of the genus Anaerococcus and Ruminococcus (MIC in range = 0.12 - 0.5 mg/mL) or strains of rods of the genus Eubacterium and Eggerthella (MIC = 0.25 mg/mL). Among Gram-positive rods the least sensitive were the strains of the genus Bifidobacterium ( MIC = 2.0 mg/mL). The tea tree oil was more active to Gram-positive than to Gram-negative anaerobic bacteria. PMID- 27180432 TI - TESTING PHARMACEUTICAL RELEASE OF ACTIVE SUBSTANCES FROM MEDICINAL PRODUCTS CONTAINING ST. JOHN'S WORT. AB - The aim of this study was to determine the content of hypericins and flavonoids in tablets and capsules containing the extract or powdered herb of St. John's wort, in herbs for infusion and herbal infusions and to release of these compounds from tablets and capsules. HPLC method was used to determine the assay of hypericins and flavonoids in all tested products. The hypericins content was between 0.35 mg and 1.44 mg per tablet or capsule. The release of hypericins from these products in the phosphate buffer of pH 6.8 is between 30 and 60% of the determined content. The degree of hypericins release from herbs into infusions was 15% on average, which corresponds to 0.64 mg of hypericins per infusion of 4 g of herbs. The flavonoids content was between 8.79 and 36.3 mg per tablet or capsule. The release of flavonoids in the phosphate buffer of pH 6.8 is between 63 and 85% of the determined content. The degree of flavonoids release was 76% on average, which corresponds to 77.0 mg per infusion of 4 g of herbs. The test results confirmed that infusions from the St. John's wort constitute are a rich source of flavonoids. At the same time, the universally accepted opinion that aqueous infusions contain only trace amounts of hypericins was not confirmed. Infusions from Herba hyperici may also be a source of hypericins in amounts comparable with the minimum dose recommended for the treatment of mild to moderate depressive episodes. PMID- 27180433 TI - PHYTOCHEMISTRY, ANTIOXIDATIVE ACTIVITY AND INHIBITION OF KEY ENZYMES LINKED TO TYPE 2 DIABETES BY VARIOUS PARTS OF AFRAMOMUM MELEGUETA IN VITRO. AB - This study investigated and compared the antioxidative, antidiabetic effects and possible active compounds present in various solvent extracts of fruit, leaf and stem of Aframomum melegueta (Rosc.) K. Schum. Samples were sequentially extracted using solvents of increasing polarity. They were investigated for 1,1-diphenyl-2 picrylhydrazyl (DPPH) radical scavenging activity, ferric reducing power, inhibition of hemoglobin glycosylation, alpha-amylase and alpha-glucosidase activities as markers of in vitro antidiabetic effects at various doses (30-240 MUg/mL). Possible compounds were analyzed using gas chromatography-mass spectrometry (GC-MS) analysis. From the results, fruit ethanolic (EtOH) extract showed higher total polyphenol (12.52 +/- 0.13 mg/g GAE) and flavonoid (4.92 +/- 0.12 mg/g QE) contents compared to other extracts. Similarly, for all the in vitro models used in this study, fruit EtOH extract exhibited lower IC50 values compared to other extracts, comparable to standards used in this study (DPPH 0.04 +/- 0.01 mg/mL; ascorbic acid: 0.03 +/- 0.02 mg/mL; gallic acid: 0.05 +/- 0.01 mg/mL; hemoglobin glycosylation: 0.7 2 +/- 0.03 mg/mL; gallic acid: 0.20 +/- 0.01 mg/mL; alpha-amylase: 0.62 +/- 0.01 mg/mL; acarbose: 4.91 +/- 0.80 mg/mL; alpha glucosidase: 0.06 +/- 0.01 mg/mL; acarbose: 0.34 +/- 0.02 mg/mL). Additionally, EtOH extract of the fruit demonstrated significantly (p < 0.05) higher reducing potentials of Fe3+ to Fe2+ compared to other solvent extracts. The GC-MS analysis of fruit and leaf EtOH extracts revealed the presence of some phenolics and other fatty acids derivatives as possible compounds present. Conclusively, fruit EtOH extract exhibited higher antioxidative and antidiabetic effects compared to other solvent extracts in vitro and thus require further work to fully validate these effects in vivo. PMID- 27180434 TI - IN VITRO ACETYLCHOLINESTERASE AND BUTYRYLCHOLINESTERASE INHIBITORY POTENTIALS OF JATROPHA GOSSYPIFOLIA PLANT EXTRACTS. AB - Inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), which breakdown acetylcholine and butyrylcholine, are considered as a promising strategy in the management of Alzheimer's disease (AD). Traditional accounts of indigenous plant Jatopha gossypyfolia suggest presence of important medicinal activities including improvement of memory functioning. To establish correlation of its use as anti-Alzheimer, AChE and BuChE inhibitory activity of extracts obtained from different parts of plant Jatropha gossypyfolia belonging to the family Euphorbiaceae were tested. Extracts from leaves, stem bark and roots were prepared by maceration. Enzyme inhibitory activity was carried out by using standard in vitro AChE and BuChE inhibition assays (Ellman's assay method) and the percentage inhibition was calculated. The results showed that roots dichloromethane fraction (65.43 +/- 0.11), roots methanol fraction (62.79 +/- 0.34) and leaves dichloromethane fraction (57.71 +/- 0.15) showed significant acetylcholinesterase inhibitory activity compared to other fractions when compared with standard serine (91.29 +/- 1.17). Similarly, butyrylcholinesterase enzyme inhibitory results showed that roots dichloromethane fraction (80.46 +/- 0.44), JGLE (77.34 +/- 0.34) showed significant BuChE enzyme inhibitory activity as compared to other fractions when compared with standard eserine (82.82 +/- 1.09). Dichloromethane extracts showed higher enzyme inhibition comparatively. Highest AChE and BuChE inhibition was observed with leaf extracts of ethyl acetate fraction. In conclusion, the plant extracts exhibited presence of bioactive compounds with significant AChE and BuChE inhibition supporting traditional use of this herb in the management of AD. However, further investigation of the plant is required. PMID- 27180435 TI - EVALUATIN OF ANTIHYPERTENSIVE ACTIVITY OF SONCHUS ASPER L. IN RATS. AB - The present investigation was carried out to evaluate the effect of aerial parts of Sonchus asper L. in normotensive, glucose and egg feed diet induced hypertensive rats. Aqueous-methanolic extract of Sonchus asper in 250, 500 and 1000 mg/kg doses was studied in normotensive and glucose induced hypertensive rats using the non-invasive technique. The results obtained showed that the extract has significantly (p < 0.5 - p < 0.001) decreased the blood pressure and heart rate in dose dependent manner. The dose 1000 mg/kg of the extract produced the maximum antihypertensive effect and was selected for further experiments. The extract was found to prevent the rise in blood pressure of egg and glucose fed rats as compared to control group in 21 days study. The LD50 of the plant extract was 3500 mg/kg b.w. in mice and sub-chronic toxicity study showed that there was no significant alteration in the blood chemistry of the extract treated rats. It is conceivable, therefore, that the aqueous-methanolic extract of Sonchus asper has exerted considerable antihypertensive activity in rats and has duly supported traditional medicinal use of plant in hypertension. PMID- 27180436 TI - ANTIOXIDANT PROPERTIES OF METHANOLIC EXTRACTS FROM THE SHOOTS AND ROOTS OF pRi TRANSFORMED PLANTS OF REHMANNIA GLUTINOSA LIBOSCH. AB - The antioxidant activity of methanolic extracts derived from shoots (HR-shoots) and roots (HR-roots) of pRi-transformed Rehmannia glutinosa plants were determined. The activity was indicated by the ability of the plant extracts to inhibit superoxide anion (O2(-.)) generation and thiobarbituric acid reactive substances (TBARS) production in resting blood platelets and platelets activated by thrombin. The strongest activity was exhibited by the HR-shoot extract (50 MUg/mL). The present study also examines the antioxidant properties of the plant extracts against human plasma lipid peroxidation induced by strong biological oxidants: hydrogen peroxide (H2O2) and H2O2/Fe. The study shows that extracts from transformed R. glutinosa plants may be a promising source of natural antioxidants, which would be valuable in various cardiovascular diseases. The extracts may also protect lipids against oxidative modifications. PMID- 27180437 TI - STUDYING THE IMPACT OF FORMULATION AND PROCESSING PARAMETERS ON THE RELEASE CHARACTERISTICS FROM HYDROXYPROPYL METHYLCELLULOSE MATRIX TABLETS OF DICLOFENAC. AB - Hydrophilic matrices, especially HPMC based, are widely used to provide sustained delivery where drug release occurs mainly by diffusion. A 3(2) full factorial design was used to develop and evaluate HPMC matrix tablet for sustained delivery of diclofenac. The influences of polymer concentration/viscosity, diluent type/ratio, drug load/solubility, compression force and pH change on drug release were investigated. Ten tablet formulations were prepared using wet granulation. HPMC K15M (10-30% w/w) was used as the polymer forming matrix. The release kinetics, compatibility studies, lot reproducibility and effect on storage were discussed. Increasing polymer concentration and compression force showed antagonistic effect on release rate. Mannitol tends to increase release rate more than lactose. Reversing diluent ratio between lactose and MCC did not affect drug release. Changing pH resulted in burst release whereas drug solubility is pH independent. F1 showed similar release to Voltaren SR and followed Higuchi model. Drug and polymer were compatible to each other. The formulation is stable at long and intermediate conditions with a significant increase in release rate at accelerated conditions due to water uptake and polymer swelling. The developed formulation was successful for a sustained delivery of diclofenac. PMID- 27180438 TI - PREPARATION AND CHARACTERIZATION OF ORALLY DISINTEGRATING LORATADINE TABLETS MANUFACTURED WITH CO-PROCESSED MIXTURES. AB - The aim of this study was to develop orally disintegrated tablets (ODT) with loratadine using Parteck ODT and Ludiflash--new commercially available tableting excipients based on co-processed mannitol. ODT containing loratadine were prepared with 3% addition of various superdisintegrants (AcDiSol, Kollidon CL-F and Kollidon CL-SF) by direct compression method. Obtained tablets were characterized for friability, pore structure, and wetting and disintegration time measured by four independents methods. In order to identify possible interactions between loratadine and the excipients, differential scanning calorimetry was used. The results showed that all formulated ODT were characterized by appropriate mechanical properties (friability < 1%), the uniform content of the drug substance and pleasant mouth feeling. Disintegration time below 30 s was observed in formulations with crospovidones as disintegrant. PMID- 27180439 TI - STUDY OF DUAL MATRIX TABLETS CONTAINING HYPROMELLOSE OF DIFFERENT VISCOSITY DEGREE AND GLYCERYL DIBEHENATE. AB - Studies are described on the compressibility of directly compressible tableting materials containing two viscosity types of hypromellose in two concentrations and tableting materials containing additional glyceryl dibehenate, also in two concentrations. Compressibility is evaluated by means of the energy profile of the compression process and determination of tensile strength of tablets. Dissolution test examines the rate of release of the active ingredient from matrix tablets, which is subsequently evaluated mathematically. Increased concentrations of both hypromelloses and an addition of glyceryl dibehenate into tablets with both types of hypromellose improved compressibility. The rate of drug release was decreased with increasing viscosity degree of hypromellose and its increasing concentration. An addition of glyceryl dibehenate exerted the same influence on release as increased concentrations of the pertinent hypromellose. PMID- 27180440 TI - IDENTIFICATION OF PHARMACEUTICAL EXCIPIENT BEHAVIOR OF CHICKPEA (CICER ARIETINUM) STARCH IN GLICLAZIDE IMMEDIATE RELEASE TABLETS. AB - In the past few years, there are number of researchers carrying out their research on the excipients derived from polysaccharides and some of these researches show that natural excipients are comparable and can serve as an alternative to the synthetic excipients. Hence, the objectives of this research are to characterize the naturally sourced chickpea starch powder and to study the pharmaceutical excipient behavior of chickpea starch in gliclazide immediate release (IR) tablets. In this research, the binding properties of chickpea starch were compared to that of povidone, whereas the disintegrant properties of chickpea starch were compared to those of crospovidone, croscarmellose sodium and sodium starch glycolate. Flow property of chickpea starch was assessed with the measurement of bulk density, tapped density, compressibility index and angle of repose. Calibration curve for gliclazide in phosphate buffer pH 7.4 was developed. Gliclazide IR tablets were then produced with direct compression method. Physicochemical characteristics of the tablets, including thickness, tablet weight uniformity, hardness, disintegration time and friability were evaluated. Then, in vitro dissolution studies were performed by following United States Pharmacopeia (USP) dissolution method. The dissolution results were analyzed and compared with t30, t50, dissolution efficiency (DE). Lastly, drug excipient compatibility studies, including Fourier transform infrared (FTIR) spectroscopic analysis and differential scanning calorimetric (DSC) analysis were carried out. Fair flow property was observed in the chickpea starch powder. Furthermore, the tablets produced passed all the tests in physicochemical characteristics evaluation except hardness and disintegration test. Additionally, in vitro dissolution studies show that chickpea starch acted as a disintegrant instead of a binder in gliclazide IR tablets and its disintegrant properties were comparable to those of crospovidone, croscarmellose sodium and sodium starch glycolate. Besides that, gliclazide was also compatible with the excipients used. Chickpea starch acted as a disintegrant in gliclazide IR tablets, instead of a binder. Therefore, chickpea starch can be a promising disintegrant in gliclazide IR tablets. PMID- 27180441 TI - A NEW APPROACH TO THE STUDY OF MUCOADHESIVENESS OF POLYMERIC MEMBRANES USING SILICONE DISCS. AB - The introduction of new test methods and the modification of existing ones are crucial for obtaining reliable results, which contributes to the development of innovative materials that may have clinical applications. Today, silicone is commonly used in medicine and the diversity of its applications are continually growing. The aim of this study is to evaluate the mucoadhesiveness of polymeric membranes by a method that modifies the existing test methods through the introduction of silicone discs. The matrices were designed for clinical application in the management of diseases within the oral cavity. The use of silicone discs allows reliable and reproducible results to be obtained, which allows us to make various tensometric measurements. In this study, different types of polymeric matrices were examined, as well as their crosslinking and the presence for the active pharmaceutical ingredient were compared to the pure dosage form. The lidocaine hydrochloride (Lid(HCl)) was used as a model active substance, due to its use in dentistry and clinical safety. The results were characterized by a high repeatability (RSD < 10.6%). The advantage of silicone material due to its mechanical strength, chemical and physical resistance, allowed a new test method using a texture analyzer to be proposed. PMID- 27180442 TI - FORMULATION DEVELOPMENT OF TOPICAL CREAM LOADED WITH ANANAS COMOSUS EXTRACT: IN VIVO EVALUATION FOR CHANGES IN SKIN BARRIER FUNCTION USING BIOPHYSICAL TECHNIQUES. AB - The prime objective of current investigation was to develop a topical skin care cream (w/o) loaded with Ananas comosus extract versus placebo control, and evaluated non-invasively for changes in skin barrier function i.e., epidermal hydration levels and transepidermal water loss (TEWL), on healthy human volunteers. Active cream carrying 2% extract of Ananas comosus in the internal phase of w/o emulsion was prepared while placebo contained no extract. Stability assessment of both creams was performed at various storage conditions 8, 25, 40 degrees C, 40 degrees C + 75% RH (relative humidity) and 50 degrees C. Effects on epidermal hydration and TEWL were observed by applying active cream at one side and placebo on the other side of face by 11 healthy human volunteers during 12 weeks period using Corneometer MPA5 and Tewameter MPA5. Results indicated that both creams (active and placebo) remained stable at all storage conditions. All samples manifested non-Newtonian, shear thinning behavior with increasing shear rate, whereas statistical interpretation indicated that effects of active cream were superior than placebo, as it significantly (p = 0.05) improves the epidermal hydration levels up to 56.74% and reduces TEWL up to -73.19% at the end of study period compared to baseline value. The surface evaluation of living skin (SELS) parameters SEr, SEsc, SEsm, SEw were also assessed and indicated a significant (p = 0.05) reduction. Conclusively, creams loaded with Ananas comosus extract exhibit better physicochemical stability and represent a propitious improvement in skin barrier function, used as a functional moisturizing and anti-aging ingredient in topical skincare products. PMID- 27180443 TI - FABRICATION AND IN VITRO EVALUATION OF 5-FLOROURACIL LOADED CHONDROITIN SULFATE SODIUM ALGINATE MICROSPHERES FOR COLON SPECIFIC DELIVERY. AB - Chondroitin sulfate and sodium alginate were incorporated in different ratios to prepare glutaraldehyde (GA) crosslinked microspheres by water-in-oil emulsion crosslinking method for delivery of 5-flurouracil (5-FU) to colon. Chemical interaction, surface morphology, thermal degradability, crystallinity evaluation, elemental analysis and drug release results were computed by using FTIR, SEM, DSC and TGA, PXRD, EXD and dissolution studies at pH 1.2, pH 6.8 and pH 7.4, respectively. Results revealed an acetal ring formation, non-porous surfaces, stability up to 450 degrees C with mass loss of 84.31%, variation in carbon and oxygen contents and targeted release at pH 7.4. Different kinetic models were applied on release studies i.e., zero order, first order, Higuchi and Korsmeyer Peppas. Higuchi model was declared as best fit model based on r2 value (0.99) and mechanism of release was non-Fickian diffusion. A potential approach for colonic delivery of 5-FU was successfully developed. PMID- 27180444 TI - COMPARATIVE BIOAVAILABILITY OF A FIXED-DOSE COMBINATION TABLET OF OLMESARTAN MEDOXOMIL/HYDROCHLOROTHIAZIDE IN HEALTHY KOREAN VOLUNTEERS. AB - Combination therapy with diuretics and angiotensin II type 1 (AT1) receptor antagonist is frequently recommended for the control of blood pressure in hypertensive patients. This study was targeted to compare pharmacokinetic profiles of a new generic fixed-dose combination (FDC) tablet of olmesartan medoxomil/hydrochlorothiazide 20/12.5 mg and a reference formulation of Olmetec Plus 20/12.5 mg tablets in healthy volunteers. The study design was a randomized sequence and two-way crossover study in healthy subjects. They were to be randomly assigned to either one of the two sequence groups; each subject sequentially received a single oral dose of reference and test tablet with 7-day washout period. Blood sample was collected at pre-dose and at 0.33, 0.67, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 h post-dose. The blood concentrations were analyzed by LC-MS/MS. Both of the 90% CI for the treatment ratios (test/reference) of C(max) and AUC(last) were to be in the range of 0.800 1.250 with regards to olmesartan medoxomil and hydrochlorothiazide; the geometric mean ratios (test/reference) for olmesartan C(max) and AUC(last) were 0.979 (90% CI, 0.934-1.027) and 0.992 (0.946-1.041), respectively, and those for hydrochlorothiazide C(max) and AUC(last) were 0.966 (0.975-1.110) and 0.999 (0.963-1.038), respectively. No serious adverse events were reported during the study. The generic formulation of olmesartan medoxomil/hydrochlorothiazide 20/12.5 mg tablet was bioequivalent with the reference formulation of Olmetec Plus 20/12.5 mg tablet in regards to the pharmacokinetic parameters of olmesartan medoxomil and hydrochlorothiazide. Clinical Research Information Service (CRIS) Registration Number: KCT0001025. (https://cris.nih.go.kr/ Mar 18, 2014) PMID- 27180445 TI - EFFECT OF GLABRIDIN AND GLYCYRRHIZIC ACID ON HISTOMORPHOMETRIC PARAMETERS OF BONES IN OVARIECTOMIZED RATS. AB - Licorice is a medicinal plant showing many therapeutic activities. Its roots contain numerous pharmacologically active compounds such as a triterpenoid saponin--glycyrrhizic acid and an isoflavan--glabridin. There are reports indicating that glabridin exhibits estrogen-like activity, therefore it can be classified into phytoestrogens, which may soothe menopause symptoms including postmenopausal osteoporosis. Due to this fact, the aim of the presented study was to evaluate the effect of glabridin and glycyrrhizic acid on histomorphometric parameters of bones in rats with ovariectomy-induced osteoporosis. The animals were divided into 6 group: (C)--control rats, (OVX)--ovariectomized rats, (OVX + E)--ovariectomized rats receiving estradiol at a dose of 0.1 mg/kg p.o., (OVX + G)--ovariectomized rats receiving genistein at a dose of 5 mg/kg p.o., (OVX + GL -ovariectomized rats treated with glabridin at a dose of 5 mg/kg p.o. and (OVX + GA)--ovariectomized rat administered with glycyrrhizic acid at a dose of 15 mg/kg p.o. Estradiol and genistein served as the positive controls in the study. Several macrometric and histomorphometric parameters were analyzed in the bones of tested rats. Obtained results indicate that glabridin shows slightly positive effect on osteoporotically changed bone tissue, and glycyrrhizic acid reveals meager influence on skeletal system with no preventive significance. PMID- 27180446 TI - NEUROMODULATORY EFFECTS OF THYMOQUINONE IN EXTENUATING OXIDATIVE STRESS IN CHLORPROMAZINE TREATED RATS. AB - The present study was undertaken to evaluate the possible protective effect of thymoquinone on chlorpromazine induced catalepsy, locomotor activity and cerebral oxidative stress in rats. The rats were divided into four groups, each group containing eight animals. The animals were evaluated after repeated administration of chlorpromazine (CPZ) 30 min before the administration of thymoquinone (TQ) for 21 days. Catalepsy was assessed using block method whereas the locomotor activity was assessed using acceleratory rotarod and actophotometer. Markers of oxidative stress parameters (LPO, GSH, GPx, GR, GST and CAT) were evaluated in the brain of rats. The cataleptic scores were significantly increased in CPZ treated rats when compared with normal control rats. Oral administration of TQ (5 and 10 mg/kg) significantly decreased cataleptic scores when compared with chlorpromazine (CPZ) treated rats. The muscle coordination and spontaneous locomotor activity was significantly decreased in CPZ treated rats when compared with normal control rats. Treatment with TQ significantly improved the muscle coordination and spontaneous locomotor activity when compared with CPZ treated rats. TQ treated rats significantly reduced the elevated levels of lipid peroxidation (LPO), increased levels of antioxidant enzymes i.e., reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST) and catalase (CAT) when compared with CPZ treated rats. The results clearly suggest that supplementation with TQ can be used to preclude CPZ induced extrapyramidal side effects and may find a role in reducing the oxidative stress. PMID- 27180449 TI - "Reflecting on care is a great way to improve it". PMID- 27180447 TI - LIPID PROFILE OF POLISH PRIMARY CARE PATIENTS AGED 35-55 YEARS LIVING IN THE DISTRICT OF PLESZEW. AB - In Poland, more than half of the adult population suffers from lipid disorders. Among the 18 million Polish people with hypercholesterolemia, over 10.8 million are unaware of this problem. To estimate the lipid profile of selected primary care patients in the district of Pleszew (Western Poland), general practitioners (GPs) recruited 681 patients aged 35-55 years in 2011. Fasting serum lipids were evaluated. We found statistically significant differences in all lipid parameters between all younger (35-45 years) and older (46-55 years) patients, between all female and male subjects, between women and men ages 35-45 years; in total cholesterol (TC), LDL-cholesterol (LDL-C) and triglycerides (TG) between younger and older female population; in HDL-cholesterol (HDL-C) and TG between women and men ages 46-55 years. Dyslipidemia, both, newly detected and previously treated, was detected in 591 patients (86.8%): 322 females (84.3%) and 269 males (90.0%). The highest percentage of lipid disorders was found in males aged 46-55 years (91.9%) and the lowest among women aged 35-45 years (78.0%). Age and gender differences in the prevalence of dyslipidemia proved of statistical importance. Among 155 patients on lipid-lowering therapy, only 28 subjects (18.1%) reached the target value of serum lipids. The prevalence of lipid disorders among primary care patients aged 35-55 years in the district of Pleszew was significantly high, and it was proved that dyslipidemia is statistically prominent in males and older patients. Polish healthcare professionals should make more efforts to improve the detection and treatment of lipid disorders. PMID- 27180448 TI - EFFECT OF THERAPY WITH ANTI-TNF alpha DRUGS AND DMARD ON DISEASE ACTIVITY AND HEALTH RELATED QUALITY OF LIFE AMONG WOMEN WITH RHEUMATOID ARTHRITIS. AB - The aim of this pilot study was to evaluate the response to 16 and 52 weeks of treatment with adalimumab and etanercept and its effect on disease activity and quality of life in patients with rheumatoid arthritis (RA). Patients were selected from 2155 medical cards of patients of Connective Tissue Health Centre (Poznan, Poland) who were refractory to conventional treatment with disease modifying anti-rheumatic drugs. To assess the disease activity, Disease Activity Score (DAS28) was used and the measurement of quality of life was evaluated with the Polish version of the WHOQoL-Bref questionnaire. To assess the disability, we have used Health Assessment Questionnaire Disability Index (HAQ-DI) and to assess the patients' pain caused by RA, Visual Analogue Scale (VAS) was used. The results of the study show a significant decrease in inflammatory activity of the disease and, consequently, an improvement in quality of life after anti-TNF alpha treatment. Results obtained with TNF-blockers after 52 weeks of treatment in RA objectively show the efficacy of these drugs and also the patients' perception of the effect on their quality of life. Study results also indicate changes in disability caused by RA and patients' pain due to disease between 16 and 52 weeks of treatment. PMID- 27180450 TI - Survey pinpoints concerns about revalidation system. PMID- 27180451 TI - New nursing strategy focuses on 10 core commitments. PMID- 27180452 TI - Latest nurse pay increases revealed in NHS report. PMID- 27180453 TI - Early indications of 'appetite' for creation of associate role. PMID- 27180454 TI - Specialist nurse pledge for Scots cancer patients. PMID- 27180455 TI - Concern growth of district nurse workforce may be 'tailing off'. PMID- 27180456 TI - Armband aids early detection of malnutrition. PMID- 27180457 TI - "We must ask patients what care and support they feel they need". PMID- 27180458 TI - "Pharmacy staff can contribute to medicines administration". PMID- 27180459 TI - A practical model for reflection on practice. AB - Although nurses are encouraged to reflect on their practice from pre-registration education onwards, many are anxious about the process and unclear how it is done or what it can achieve. This article discusses approaches to reflection and presents a new, triangular model of reflection that encourages nurses to share their reflections and helps to ensure they gain useful insights from the exercise. PMID- 27180460 TI - Better endings: a review of end-of-life services. AB - The NHS has undertaken research on the organisation and quality of end-of-life services, which provides valuable insights for those planning and delivering care for people approaching the end of life, and their families. The review of the findings, structured around the right care in the right place at the right time, highlights what is already known, and how research that is currently underway will address key gaps and uncertainties for frontline staff and clinical leaders. This article summarises the findings outlined in that review. PMID- 27180461 TI - Power inequality between patients and nurses. AB - Many factors can result in an imbalance of power between patients and nurses. This can have a range of negative effects on patients' experience of care. This third article in a seven-part series on the use of patient narratives to reflect on care focuses on power inequalities and their effects, and suggests points that nurses can use to reflect on their own practice. PMID- 27180462 TI - Twelve-hour shifts: burnout or job satisfaction? AB - Job satisfaction and burnout in the nursing workforce are global concerns. Not only do job satisfaction and burnout affect the quality and safety of care, but job satisfaction is also a factor in nurses' decisions to stay or leave their jobs. Shift patterns may be an important aspect influencing wellbeing and satisfaction among nurses. Many hospitals worldwide are moving to 12-hour shifts in an effort to improve efficiency and cope with nursing shortages. But what is the effect of these work patterns on the wellbeing of nurses working on hospital wards? This article reports on the results of a study performed in 12 European countries exploring whether 12-hour shifts are associated with burnout, job satisfaction and intention to leave the job. PMID- 27180463 TI - Pharmacotherapy: anxiety and comorbid alcohol use. PMID- 27180465 TI - Put support into practice. PMID- 27180464 TI - 60 second with Laura Croan. PMID- 27180466 TI - Bridging the Gap between Innovation and Financing. Chicago 2015 Health Venture Fair Awards. PMID- 27180467 TI - YACHIYO HOSPITAL; Center of SUPER CARE MIX--Comprehensive Care from Emergency to Home for the community. AB - Anjo City has two general hospitals. Kosei Hospital, a central medical center for advanced care, and our Yachiyo Hospital for regional care. Recently, Kosei Hospital faced over-capacity problem because of overflow in emergency visits and congested wards due to shortage of post-acute beds. We planned a project to ease the congestion of the central hospital and manage post-acute patients. PMID- 27180468 TI - Construction and Application of a Refined Hospital Management Chain. AB - Large scale development was quite common in the later period of hospital industrialization in China. Today, Chinese hospital management faces such problems as service inefficiency, high human resources cost, and low rate of capital use. This study analyzes the refined management chain of Wuxi No.2 People's Hospital. This consists of six gears namely, "organizational structure, clinical practice, outpatient service, medical technology, and nursing care and logistics." The gears are based on "flat management system targets, chief of medical staff, centralized outpatient service, intensified medical examinations, vertical nursing management and socialized logistics." The core concepts of refined hospital management are optimizing flow process, reducing waste, improving efficiency, saving costs, and taking good care of patients as most important. Keywords: Hospital, Refined, Management chain PMID- 27180469 TI - Quality, Safety and Patient Centered Care--A Dream Come True in the Mountains of Northern Pakistan. An Award winning project of "2015 Quality, Safety & Patient Centered Care Award" at, Chicago USA. AB - Northern Pakistan remains very challenging terrain due to harsh weather all year round presenting an infrastructura, human resource and supply chain challenge of its own. Many times the facility had to move to different locations on emergency and ad hoc basis due to landslides, earthquakes affecting continuity of care. Providing quality healthcare to often resource constraint hard-to-reach areas has always been AKHS,P's unique forte. Breaking barriers for catchment population to access quality healthcare, AKHS,P embarked on an initiative of implementing, achieving and sustaining ISO 9001:2008 Quality Management System international standards certification. This article shares the unique experience of AKHS,P in achieving and sustaining ISO 9001:2008 International Quality Management System Certification. After untiring efforts and the hard work of ground staff; AKHS,P achieved ISO 9001:2008 International Quality Management System Certification as well as 1st Surveillance Audit which itself proved that AKHS,P sustained quality systems and ensured continuous quality improvement in the Mountains of Northern Pakistan. PMID- 27180470 TI - St. Luke's Medical Center Global City--Global Trigger Tool (GTT) Project. AB - The Global Trigger Tool (GTT) was developed by the Institute of Healthcare Improvement (IHI), to identify and measure the rate of adverse events over time in a healthcare facility. It is a sampling methodology that utilizes "triggers" in the detection of random adverse events and harms and it also measures the adverse events overtime. The Quality and Patient Safety Group of St. Luke's Medical Center--Global City initiated the implementation of the Global Trigger Tool as a proactive solution using retrospective information gathered to address the growing challenge that adverse events and harms impose in the institution with the ultimate goat of improving patient safety. St. Luke's Medical Center Global City is the first and only hospital in the Philippines to implementand utilize the Global Trigger Tool. PMID- 27180471 TI - Paradigm of Professional Integration for Disabled People in Fundacio Integralia Valles: Key Success Factors. AB - Fundacio Integralia Valles is a pioneer contact center in Europe that has involved the creation of a healthcare reference center managed exclusively by people with disabilities and degenerative diseases to enable their professional development and ultimately integration into the labour market. The environment created under this project enables effective training and building of skills, capacity and work experience as well as promoting social responsibility among a population group that is at risk of exclusion. The major differentiating factor in Fundacio Integralia Valles is the quality of service provided by its staff, who are particularly sensitive to the issues of health, and who provide professional and human dimension in every attention. PMID- 27180472 TI - Cognitive Training for Dementia Patients in the Community & Art Therapy Programs of 'Goyang Centenarian's Good Memory School'. AB - Myong Ji Hospital has launched the 'public health Service project team' for the first time in Korea as a private institution to carry forward and administer public health projects and services in a more structured way. Notably, Goyang Centenarian's Good Memory School has deliberately provided various art therapy programs to those who have a high risk of dementia in pursuit of promoting dementia prevention, and maintaining a positive mind and healthy body for any required daily activities for senior living. Participating patients have expressed remarkable satisfaction, and the art therapy programs have not only shown the effectiveness of strengthening the mental status of the cognitively impaired patients but have also proposed a feasible non-pharmacological therapy option, which promotes the quality of their daily living and lowers the burden for their caregivers. PMID- 27180473 TI - Why Hospitals and Payers are Recommending Home Care Upon Discharge Instead of SNF or Traditional Home Health Services--Alternative Payment Model Hospital Incentives Aligning with Patient Choice. AB - Seniors and other hospital patients in the United States have traditionally had the option of being discharged to a skilled nursing facility (convalescent home) for post-acute services, or home with nursing and therapy services provided in the home setting. Traditionally, these home based services have been referred to as "home health." As more Americans have retired, home health services have expanded and are readily accessible. This growth put tremendous stress on the Medicare fund which pays for senior care services. However, "Home Care," which traditionally has been viewed as non-medical home based services, has also become a booming industry for the cost conscious in recent years as more Americans reach retirement age. With the passing of the Affordable Care Act in 2010, providers and payers are now finding themselves responsible for post-acute care and continuous patient health, so cost efficient solutions for post-acute care are thriving. For the first time in history, American hospitals and Insurers are recognizing Home Care as an effective model that achieves the Triple Aim of Health Care reform. Home Care, which is no longer completely non-medical services, has proven to be an integral part of the care continuum for seniors in recent years and is now becoming a viable solution for keeping patients well, while still honoring their desire to age and heal at home. This paper analyzes the benefits and risks of home care and provides a clear understanding as to why American hospitals are emphasizing SNF Avoidance and skipping home health, opting instead to refer patients directly to home care as the preferred discharge solution in a value based model. PMID- 27180474 TI - The Power to drive change: Working together for excellence. Creating a continuously improving consumer engagement framework for excellence in patient centered care. AB - The World Health Organization has acknowledged Patient Safety while receiving hospital care as a serious global public health issue, with patient empowerment and community engagement key to continuously improving safety and quality of care for the best possible clinical and patient outcomes. In Australia, the introduction of ten mandatory National Safety and Quality Health Service Standards in 2011 provided the catalyst for all Australian health facilities to review their systems. Standard 2: Partnering with Consumers required health facilities across Australia to assess commitment to, and capacity for consumer and community engagement and participation. At this time, the Royal Brisbane and Women's Hospital did not have a strategic perspective and understanding, or an organizational structure for engaging with consumers (patients, families, care givers and community members). The concept required a new model to replace the clinician-led model of healthcare historically featured in Australia, with a change in culture and core business. processes to partner with consumers at all levels of the system, from individual patient care through to participating in policy development, health service planning and delivery, and evaluation and measurement processes. The challenge for the hospital was to build a sustainable framework of engagement for a genuine patient-centered model of care informed by best practice, and provide leadership and commitment to developing as an area of excellence in patient engagement and experience. A successful and sustainable framework for consumer and community engagement has been embedded in the hospital, with resultant culture change, achieving accreditation across all core and developmental criteria for the partnering with consumer standards including several Met with Merit ratings. PMID- 27180475 TI - Decreasing Interferences and Time Spent on Transferring Information on Changing Nursing Shifts. AB - The exchange of clinical information on patients is a common component in nursing shift changes where professionals have limited time to transfer this information. There is no standardized or structured methodology for transferring information, which requires increased time to complete. Also, during the exchange, some interruptions can disrupt the communication among professionals, which can affect the patient's safety. A descriptive study was developed for five months, the information transfer arrangement among nurses was changed in order to determine which interruption increased the time spent on shift change and, therefore, decreased the safety of pediatric patients. The results obtained on the type of interruption caused us to rethink the organization that includes pediatric patient care. PMID- 27180476 TI - Improvement Initiatives of Resuscitation Service in a Regional Rehabilitation Hospital in Hong Kong. AB - Limited accessibility to resuscitation equipment and non-standardized instrument layout in trolleys would cause difficulty for the team members to access appropriate emergency equipment for delivering prompt resuscitation service in Tung Wah Eastern Hospital (TWEH). Improvement initiatives were implemented in September 2012 after endorsement by the resuscitation subcommittee: (i) standardization and installation of resuscitation equipment including resuscitation trolleys, emergency drug kits, automatic emergency defibrillators, designated response team (DRT) kit; (ii) guidelines revision involves the workflow, staff deployment, and designated areas for resuscitation during different service hours and (iii) staff training by workshop and video. Periodic resuscitation drill was held to monitor staff performance after training and the debriefing provided a chance for discussion and feedback from frontline staff. The compliance audit result for this exercise and the staff performance in the drills were improved, showing that the initiatives were successful. KEY WORDS: Resuscitation, Accessibility, Standardization, Drill. PMID- 27180477 TI - Improving the Success of Strategic Management Using Big Data. AB - Strategic management involves determining organizational goals, implementing a strategic plan, and properly allocating resources. Poor access to pertinent and timely data misidentifies clinical goals, prevents effective resource allocation, and generates waste from inaccurate forecasting. Loss of operational efficiency diminishes the value stream, adversely impacts the quality of patient care, and hampers effective strategic management. We have pioneered an approach using big data to create competitive advantage by identifying trends in clinical practice, accurately anticipating future needs, and strategically allocating resources for maximum impact. PMID- 27180478 TI - [No longer an individual fate]. PMID- 27180479 TI - [The legal minimum wage and its effects. Consequences for the recruitment of skilled personnel from third world countries]. PMID- 27180480 TI - [Not Available]. PMID- 27180481 TI - [Competition for low wages. Nursing minimum wage prevents the worst in nursing]. PMID- 27180482 TI - [Minimum wage.... exacerbates shortage of skilled nurse shortage, moonlighting and unemployment]. PMID- 27180483 TI - [Prevention and treatment of dementia. It depends on nutrition]. PMID- 27180484 TI - [Cognitively impaired patients in the hospital. A challenge for personnel]. PMID- 27180485 TI - [The environment determines the behavior. Persons with dementia in the hospital]. PMID- 27180486 TI - [Pads and wraps for persons with dementia. "Not everything is cut and dried"]. PMID- 27180487 TI - []Those from the shelter and we. Living together in the residence district]. PMID- 27180488 TI - [Long-term geriatric nursing. Mobility concept in the Bremen Home Foundation]. PMID- 27180489 TI - [Research at the German Center for Neurodegenerative Diseases. Questions on the management strategies for persons with dementia]. PMID- 27180490 TI - [Responsibilities of modern facility management in NRW. Complexity justifies academic education]. PMID- 27180491 TI - [Not Available]. PMID- 27180492 TI - [Interview with the graduate engineer Andreas Kitzig. "Useful and sensible features"]. PMID- 27180493 TI - [Assuring nursing competence in education. Contribution for improving persons with dementia in clinics]. PMID- 27180494 TI - [Practicum during education. New occupational impulses]. PMID- 27180495 TI - [Demand and nursing provision of key supporting points in Baden-Wurttemberg]. PMID- 27180496 TI - Active and passive smoking linked to infertility and early menopause. PMID- 27180497 TI - Controlling joint pain in older people. AB - Jont pain in oldder people The prevalence of chronic pain in older people in the community ranges from 25 to 76% and for those in residential care, it is even higher at 83 to 93%. The most common sites affected are the back, hip, or knee, and other joints. There is increased reporting of pain in women (79%) compared with men (53%). Common conditions include osteoarthritis and, to a lesser extent, the inflammatory arthropathies such as rheumatoid arthritis. The differential diagnosis includes non-articular pain such as vascular limb pain and nocturnal cramp, some neuropathic pain conditions (such as compressive neuropathies and postherpetic neuralgia), soft tissue disorders such as fibromyalgia and myofascial pain syndromes. In addition to an assessment of pain intensity, a biopsychosocial model should be adopted to ascertain the effect of the pain on the patient's degree of background pain at rest. The disease is often localised to the large load-bearing joints, predominantly the hips and knees. In contrast to osteoarthritis, the inflammatory arthritides typically present with symmetrical swollen, stiff, and painful small joints of the hands and feet, usually worse in the morning. PMID- 27180498 TI - Anxiety in older adults often goes undiagnosed. AB - Anxiety disorder in the elderly is twice as common as dementia and four to six times more common than major depression. Anxiety is associated with poorer quality of life, significant distress and contributes to the onset of disability. Mortality risks are also increased, through physical causes, especially cardiovascular disease, and suicide. Diagnosing anxiety disorders in older adults remains a challenge because of the significant overlap in symptoms between physical disorders (shortness of breath; abdominal and chest pain; palpitations) and depression (disturbed sleep; poor attention, concentration and memory; restlessness). Good history taking is crucial in elucidating whether the complaint is of new onset or a recurrence of a previous disorder. The presence of comorbid depression should be clarified. If present, its temporal relationship with the anxiety symptoms will indicate whether there is an independent anxiety disorder. A medication review is warranted, as a number of drugs may be causative (calcium channel blockers, alpha- and beta-blockers, digoxin, L-thyroxine, bronchodilators, steroids, theophylline, antihistamines) or may cause anxiety in withdrawal (e.g. benzodiazepines). Substance and alcohol abuse should be excluded, as withdrawal from either may cause anxiety. A new or exacerbated physical illness may be related to anxiety. Medical investigations will help clarify the extent to which a particular somatic symptom is the result of anxiety. PMID- 27180499 TI - Improving the detection and management of type 1 diabetes. AB - Type 1 diabetes affects around 370,000 adults in the UK, about 10% of all those diagnosed with diabetes. In type 1 diabetes there is a lack of beta cell insulin secretion as a result of autoimmune destruction of the beta cells. However, patients are not affected by insulin resistance, and so do not routinely experience the features of metabolic syndrome that occur in type 2 diabetes. NICE recommends considering further investigation with autoantibody testing or measurement of C-peptide when: type 1 diabetes is suspected but the presentation includes atypical features (e.g. age >=50, BMI >= 25 kg/m2, slow evolution of hyperglycaemia or long prodrome); type 1 diabetes has been diagnosed and treatment started but there is a clinical suspicion that the patient may have a monogenic form of diabetes, and C-peptide and/or autoantibody testing may guide the use of genetic testing; classification is uncertain, and confirming type 1 diabetes would have implications for therapy. Structured education is the cornerstone of care providing tools to allow effective self-management. Following a new diagnosis of type 1 diabetes structured education should be offered within 12 months. Newly diagnosed patients should be offered a regimen including a basal (long-acting) insulin with bolus (rapid-acting) insulin given at mealtimes. The optimal regimen, which should be offered from diagnosis, is a combination of twice daily insulin detemir and a rapid-acting analogue given at mealtimes. However, where glycaemic control is already optimised on an alternative insulin regimen this should not be discontinued. PMID- 27180500 TI - Skin conditions in children. PMID- 27180501 TI - AETIOLOGY OF WAR NEUROSES. PMID- 27180502 TI - Mobile phones have transformed GP care. PMID- 27180503 TI - EEG and Coma. AB - Coma is defined as a state of extreme unresponsiveness, in which a person exhibits no voluntary movement or behavior even to painful stimuli. The utilization of EEG for patients in coma has increased dramatically over the last few years. In fact, many institutions have set protocols for continuous EEG (cEEG) monitoring for patients in coma due to potential causes such as subarachnoid hemorrhage or cardiac arrest. Consequently, EEG plays an important role in diagnosis, managenent, and in some cases even prognosis of coma patients. PMID- 27180504 TI - What Is the Frequency of Intraoperative Alerts During Pediatric Spinal Deformity Surgery Using Current Neuromonitoring Methodology? A Retrospective Study of 218 Surgical Procedures. AB - INTRODUCTION: There is variability in intraoperative neuromonitoring (IONM), anesthetic and surgical techniques for the treatment of pediatric spinal deformity. This study evaluates a series of patients treated at multiple centers utilizing transcranial motor and somatosensory evoked potentials (TcMEP and SSEP) and electromyography (EMG). The frequency of alerts and the intraoperative follow up is reported. METHODS: Standard patient demographics and IONM data were collected from a two-month cohort of pediatric spine deformity cases. RESULTS: Data from 218 scoliosis patients were included from 46 facilities and 72 surgeons. Baseline upper and lower extremity TcMEP data were present in 96.7% and 93.9% patients respectively. Baseline upper and lower SSEPs were present in 99.5% and 95.4% respectively Surgical TCMEP alerts occurred in 19 (8.7%) patients during deformity correction (n = 11), placement of instrumentation (n = 5), decompression (n = 2), and closing (n = 1) with concurrent SSEP alerts occurring in five patients. Nine had TCMEP recovery, eight showed partial recovery and two did not recover. Additional alerts occurred due to: positioning (n = 16), inhalational agent change (n = 4), global physiological change (n = 4) and technical reasons (n = 2). A total of 2164 pedicle screws were tested. Of 197 (9.1%) screws that tested from 6-9 mA, 171 (65.4%) were left unchanged, 10 (51%) removed, eight (4.1%) repositioned with improved threshold, and eight (4.1%) without improvement. Of 26 screws that tested <= 5 milliamperes (mA), 17 (65.4%) were left unchanged, five (19.2%) removed, two (7.7%) repositioned with improved threshold, and two (7.7%) without improvement. CONCLUSIONS: IONM provides data that causes re-evaluation in about 10% of pediatric spinal deformity cases. PMID- 27180505 TI - Rhythmic Midtemporal Discharge in a Youth During Light Sleep. AB - Rhythmic midtemporal discharge (RMTD) is a rare, benign EEG pattern that may have epileptic morphology. Recognizing variations of RMTD is important in order to avoid over- or misinterpretation of EEG findings, which may lead to inappropriate treatment and negative consequences for the patient in question. We present a case report of RTMDs during light sleep where initial erroneous description necessitated repeat EEGs and additional diagnostic exams and led to the postponement of obtaining a drivers licence for this young patient. PMID- 27180506 TI - The Significance of REM Sleep on Routine EEG. AB - The objective of this study was to report on sleep-onset REM period (SOREMP) during routine EEG and conditions associated with it at a comprehensive epilepsy program. We retrospectively reviewed all outpatient and inpatient EEGs performed at Tampa General Hospital, a comprehensive epilepsy center over a four-month period. All EEGs were reviewed by experienced board-certified epileptologists. When SOREMP was identified, the chart was reviewed to identify the most likely etiology and the associated conditions that might be contributing. A total of 449 EEGs were reviewed between August 10, 2009, and December 9, 2009. Of those, 106 were outpatient EEGs and 343 were inpatient EEGs. There were 7 EEGs with SOREMP identified, 6 from inpatient EEGs, and 1 from an outpatient EEG. Thus, SOREMP was more common in the inpatinent setting than outpatient. There is an association of SOREMP with sleep deprivation and drug withdrawal. PMID- 27180507 TI - "You Won't Get Fooled Again": BSSS, SSS, or BETS: Another Benign Sharp Variant That Could Be Mistaken as Epileptogenic. PMID- 27180508 TI - [The effects of narcissism and self-esteem on immersion in social network games and massively multiplayer online role-playing games]. AB - Recent research has shown growing interest in the process by which narcissism triggers immersion in social network games (SNG). Highly narcissistic individuals are motivated not only by the achievement of goals and monopoly of materials (i:e., self-enhancement), but also by comparison and competition with others (i.e., social comparison) We predicted that the common rules and environments of SNG and massively multiplayer online role-playing games (MMORPG), such as systems of exchanging items and ranking players, facilitate immersion of highly narcissistic individuals during the game. Structural equation modeling of data from 378 SNG players and 150 MMORPG players recruited online showed that self esteem inhibited game immersion, whereas narcissism increased game immersion via motivation for goal attainment. SNG players were more likely to be immersed in the game via motivation for goal attainment than MMORPG players. These findings suggest that, compared with MMORPG, the environments of SNG provide strong incentives not for those high in self-esteem who seek acceptance of others, but for those high in narcissism who are motivated by self-enhancement via competition with others. PMID- 27180509 TI - [The price-based certainty of purchase influences consumer behavior for discount]. AB - Tversky & Kahneman (1981) reported that most participants decided to drive when they could save money on a low-price good as compared to when they could save on a high-price good, even though the discount prices were same. Although this irrational decision making has been interpreted as a rate-dependent estimation of value (prospect theory), this study newly proposes that it can be explained by the certainty of purchase based on the price of goods. Experiment 1 replicated the previously reported difference in decision making, and additionally demonstrated that participants' certainty of purchase was lower for a high- than a low-price good. When it was emphasized that participants' intention to purchase high- and low-price goods were equally sure, decision making did not significantly differ (Experiment 2). Furthermore, decision making differed based only on the certainty of purchase even,when prices of goods were-same (Experiment 3). Consumers' decision making may be rather rational, depending straightforwardly on the certainty of purchase that is susceptible to price. PMID- 27180510 TI - [The effect of humor in the workplace on mental/physical health and self evaluation of job performance]. AB - In this study we aimed to examine the contents of humor in the Japanese workplace and to understand the effects of humor on mental/physical health and self evaluation of job performance. Japanese workers (N = 436) responded to questionnaires addressing workplace humor, feelings about workplace, workplace communication, mental/physical health, and perceived job performance. An exploratory factor analysis indicated that there are five types of workplace humor: norm-violating humor, experience-sharing humor workplace-enjoying humor, people-recalling humor, and outside-mocking humor. A covariance structural analysis showed that norm-violating humor and workplace-enjoying humor decreased mental and physical health by promoting both negative feelings in the workplace and self-disclosure about the negative side of work. Results also revealed that experience-sharing humor, people-recalling humor, and outside-mocking humor had a positive effect on the self-evaluation of job performance as well as mental and physical health, by promoting both positive feelings and mutual communication in the workplace. Results suggest that humor in the workplace has various influences on workers depending on the type of workplace humor. PMID- 27180511 TI - [The effect of suggestibility on eyewitness identifications: A comparison between showups and lineups]. AB - There are two types of eyewitness-identification procedures: showups and lineups. Although the false-identification rate of showups was considered to be higher than that of lineups, experimental research has not always supported the superiority of lineups. Further, suggestibility of showups is believed to produce higher false-identification rates, but no experimental study has manipulated suggestibility. In this study, we manipulated suggestibility; 258 participants performed photo identification in a showup or lineup. The results revealed that the correct-identification rate was higher in the showups than the lineups, and the rate of dangerous false identification for the innocent suspect did not differ between showups and lineups. In lineups alone, the false-identification rate of the high-suggestibility.condition was marginally higher than that of the low-suggestibility condition. The results indicate that suggestibility, which results from the preconception that the perpetrator must exist in the photos, increases false identifications in relative judgments, such as in lineups. PMID- 27180512 TI - [Mother's attributions regarding children's behavior and maltreatment]. AB - This study aimed to compare maltreating mothers and non-maltreating mothers on attributions and affects related to child behaviors. It also assessed how attributions predict affective and behavioral reactions to child behaviors. The study population comprised of a community-based sample of mothers with children aged 2 to 4 years (n = 238). Mothers' attributions and affect were assessed using vignettes of child behavior. They also answered questions about their maltreating parenting behaviors and demographic factors such as childcare environments. Results highlighted that, as compared with non-maltreating mothers, maltreating mothers made more intentional and stable attributions to negative child behavior, and to report more anger and aversion. They also had a tendency to report less happiness toward positive child behavior. Additionally, path analyses documented a pattern of thinking-feeling-action linkages. It was revealed that attributions regarding children's behavior influenced negative affect and that negative affect in turn predicted maltreatment. Finally, the usefulness of a cognitive approach to maltreating mothers, and the implications of the findings as a model for intervention are discussed. PMID- 27180513 TI - [Development of the Feelings toward Nature Scale and relationship between feelings toward nature and proximity to nature]. AB - In the field of environmental psychology, there is rapidly growing interest in the concept of connectivity with nature, describing an individual's sense of being connected with nature. The author developed a new scale for assessing feelings toward nature, including connectedness. Confirmatory factor analysis indicated a five-factor model consisting of restorativeness, oneness, mystery, care, and aversion. Then, the relationships among availability of nature in respondents' neighborhood, age, and each subscale score of the Feelings toward Nature Scale, were analyzed using structural equation modeling. The availability of nature in neighborhoods was assessed using a geographic information system and respondents' subjective evaluations. Results indicate that overall connectedness to nature is weaker as availability of nature decreases, as assessed by subjective evaluation. Results also suggest that aversion toward nature in younger people is relatively stronger than in older generations. PMID- 27180514 TI - [Effects of situational and individual variables on critical thinking expression]. AB - The present study examined when people decide to choose an expression that is based on critical thinking, and how situational and individual variables affect such a decision process. Given a conversation scenario including overgeneralization with two friends, participants decided whether to follow the conversation by a critical-thinking expression or not. The authors controlled purpose and topic as situational variables, and measured critical-thinking ability, critical-thinking disposition, and self-monitoring as individual variables. We conducted an experiment in which the situational variables were counterbalanced in a within-subject design with 60 university students. The results of logistic regression analysis showed differences within individuals in the decision process whether to choose a critical-thinking expression, and that some situational factors and some subscales of the individual measurements were related to the differences. PMID- 27180515 TI - [Development the Japanese of the Self-Compassionate Reactions Inventory]. AB - Self-compassion is defined as being compassionate towards the self in times of suffering, and is composed of the following three components: self-kindness, common humanity, and mindfulness. This article reports the development of the Japanese version of the Self-Compassionate Reactions Inventory (SCRI-J). The SCRI J measures self-compassion based on the degree to which people choose self compassionate reactions to 8 hypothetical hardships. Study 1: (N = 179) showed that the SCRI-J had sufficient internal consistency. In terms of its validity, results showed a positive correlation between the SCRI-J and the Japanese version of the Self-Compassion Scale, supporting its concurrent validity. In addition, the SCRI-J was positively correlated with self-esteem and negatively correlated with psychological stress responses. Moreover, the association between the SCRI-J and stress responses remained significant when the effect of self-esteem was removed. In Study 2 (N = 90), the SCRI-J demonstrated high test-retest reliability over 3 weeks. Overall, the present study indicates that the SCRI-J has sufficient reliability and validity as a new scale for self-compassion. PMID- 27180516 TI - [Development of Japanese versions of the Daydream Frequency Scale and the Mind Wandering Questionnaire]. AB - This study developed and examined the validity of Japanese versions of the Daydream Frequency Scale (DDFS) and the Mind Wandering Questionnaire (MWQ), which measures propensity for spontaneous thoughts and mind wandering, respectively. In Study 1, we translated the items of the DDFS and the MWQ into Japanese and verified their validity. In Study 2, we confirmed the correlation of both scales with mind wandering, as measured by thought sampling during an attention demanding task. These two studies revealed a dissociation between the properties of the scales; while DDFS reflects propensity for spontaneous thoughts, MWQ specifically reflects propensity for mind,wandering. We discuss the usefulness of the DDFS and the MWQ for studying the psychological functions of spontaneous thoughts and mind wandering. PMID- 27180517 TI - [Do regional and generational differences in attitudes toward "Luck Resource Belief" exist?]. AB - This article examines whether belief in superstitions and folklore differs by age and degree of modernization specifically. This study investigated regional and generational differences in attitudes toward "Luck Resource Belief," a notion regarding luck. The 500 Japanese participants in our sample were stratified by place of residence, age, and income. The results reflected gender differences, but not regional or generational differences with regard to the "Luck Resource Belief" scale scores. Based on these results, the hypothesis that the mass media plays a major role in the dissemination of information about superstitions and folklore is discussed in this context. PMID- 27180518 TI - [The hierarchical semantic structure of respect-related emotions in modern Japanese people]. AB - This study examined the reproducibility of the hierarchical semantic structure of respect-related emotions and the prototypical meaning of sonkei (respect) in modern Japanese people. Participants, ages 20-79, rated the semantic similarity of 153 pairs of 18 respect-related words used in previously published work. Hierarchical cluster analysis (n = 515) showed almost the same semantic organization as the previous study. The highest level of abstraction consisted of "person-focus respect, emotional attitude" and "action-focus respect, emotional state." The basic-level consisted of (a) respect mingled with mild love; (b) ought-respect (respect as moral duty); (c) idolatry (worship and adoration); (d) awe mingled with fear; (e) admiration; and (f) wonder. The word sonkei was included in category (a). Additional analyses were conducted according to age. The results revealed that the basic categories seen in adults ages 60-79 differed from those in the whole sample and that sonkei was included in the category which could be considered as, ought-respect. These findings suggest that the semantic organization of respect-related emotions is gradually changing under the influence of modern culture. PMID- 27180519 TI - Social Work 2.0: Upgrading Terminology in the Profession. PMID- 27180520 TI - Curriculum ad Psychoeducational Groups: Opportunities and Challenges. AB - Curriculum and psychoeducational groups have become increasingly popular because of their strong evidence base and presumed ease of implementation. The curriculum provides a valuable guide to social workers leading groups as they decide on topics for discussion. Typically, the literature emphasizes the content--the material being presented--over the process: the ways in which members interact with one another and with the leader. The authors of this article contend that when the social worker adheres too rigidly to the content, members' ability to make meaning of and internalize the information being presented is compromised. They advocate for an approach to group facilitation that emphasizes flexible presentation of curriculum topics. The benefits of group participation are maximized when collaborative learning, which involves members' interactions with one another and the leader, is encouraged. The article includes a summary of the theoretical foundation and evidence base of psychoeducational and curriculum groups and presents strategies to promote collaborative learning using case examples. PMID- 27180521 TI - Professional Resistance in Social Work: Counterpractice Assemblages. AB - The goal of this article is to deepen understanding of the concept of professional resistance. Studies show that social workers in various parts of the world are increasingly confronted with regulations, programs, and policies that challenge their ability to carry out their professional mission in an ethical manner. Social workers may also find themselves under the pressure of periodic retrenchment resulting from budgetary constraints and subjected to worsening working conditions and threats of wage or social benefit reduction. Therefore, it is not surprising that social workers are sometimes required to engage in actions to oppose these negative realities or, in other words, to practice professional resistance. However, despite its growing relevance, the term "professional resistance" remains both theoretically obscure and marginal to social work practice. This article traces the presence of the concept in social work history, examines divergent uses of the concept in social work literature, introduces theoretical perspectives that may help practitioners enlarge their professional repertoire, provides concrete cases of resistance in different contexts, and finally proposes some paths to professional resistance. PMID- 27180522 TI - Latino Critical Perspective in Social Work. AB - Although a Latino critical perspective (LatCrit) is consistent with social work's professional mission and values, it is largely absent from its literature. With a focus on the Latino population in the United States, LatCrit elucidates an oppressive structure of social inequality and discrimination and promotes systemic change through self-advocacy. Thus, LatCrit supports the call for the revival of mezzo- and macro-level practice in social work. This article discusses the utility of LatCrit for social work practice through a discussion of its origins, main tenets, and primary aims. A critique of the theoretical perspective is also offered; its insights for social work practice, philosophical assumptions, and challenges for use in the field are highlighted. Social workers are offered an analysis of LatCrit enabling them to apply the theoretical perspective discretionarily rather than universally to meet diverse challenges and client needs. Specific ways in which social workers can facilitate the LatCrit praxis are discussed, such as community organizing and grassroots advocacy campaigns. PMID- 27180523 TI - "The Pain of Exile": What Social Workers Need to Know about Burmese Refugees. AB - Refugees from Burma have comprised the largest group of refugees resettling in the United States over the past decade, with nearly 90,000 people, and 19 percent of the total refugee population. However, very little literature exists that describes the cultural context and displacement experiences of this population. This article addresses that gap in the literature by examining historical, social, political, and cultural dimensions relevant to social work practice with Burmese refugees. Practice with Burmese refugees should be informed by knowledge of refugee policy, refugee resettlement, and social services delivery systems; the Burmese historical and political context; the community's specific strengths, needs, and cultural diversity; and human rights and social justice issues. Strong community partnerships between social workers and indigenous community leaders, between resettlement agencies and ethnic community-based organizations, and between different Burmese refugee groups are important to meeting short- and long term social services needs and fostering successful adaptation and community integration. PMID- 27180524 TI - Impact of Head Start's Entry Age and Enrollment Duration on Children's Health. AB - This secondary data analysis examined the association of Head Start children's entry age and enrollment duration on children's dental, vision, and hearing health based on data from 60 local Head Start classrooms. Children were divided into three groups: One group of children entered Head Start at age three and maintained enrollment for one year (Group 1). The second group of children entered Head Start at age four and stayed one year (Group 2). The third group of children entered at age three and stayed in Head Start for two years (Group 3). Compared with Group 3, Group 1 had fewer dental problems and Group 2 had less identified hearing problems. Children's gender, ethnicity, and program characteristics and family risk factors were associated with health problems. PMID- 27180525 TI - Homeless Youths' Caretakers: The Mediating Role of Childhood Abuse on Street Victimization and Housing Instability. AB - Homeless youths who live on the streets are particularly vulnerable to victimization and continued homelessness. Identifying factors associated with housing stability and victimization while homeless can offer useful guidance for those who serve these youths. The current study examined the relationship between multiple caretakers and the unique effect of childhood abuse (physical, sexual, neglect) on past-year housing and victimization experiences. Seventy-nine substance-using, street-living youths ages 14 to 24 years completed the survey. Findings confirmed a relationship between multiple caretaker transitions and childhood sexual abuse and neglect, but not physical abuse. Sexual abuse was further associated with higher street victimization and reduced housing stability. In addition, sexual abuse mediated the relationship between multiple caretakers and past-year victimization and housing instability. These findings suggest that sexually abused homeless youths are at particular risk for future victimization and housing instability compared with other youths, and specialized intervention for these youths is indicated. PMID- 27180526 TI - Statutory Compensation for the Wrongly Imprisoned. AB - This article provides an overview of the unique challenges faced by men and women who have been wrongly convicted, imprisoned, and subsequently exonerated, and discusses the relevance of social work to exoneration. The ways in which exonerees can seek compensation are described, and state compensation statutes are examined, delineating monetary and reentry support provisions. Currently, 30 states and the District of Columbia have compensation statutes. Monetary and reentry support provisions vary greatly by state, with few providing both. The wrongly imprisoned experience the same effects of incarceration as other prisoners; their psychological trauma, however, is exacerbated by the fact that they are innocent. Furthermore, upon release, exonerees have fewer reentry supports available to them compared with prisoners released on parole. This article supports the position that the state has a responsibility to provide adequate compensation, monetarily and servicewise, to the wrongly imprisoned, and that compensation by statutory means should be standard in every state. This article also highlights how social workers are uniquely qualified to provide immediate and long-term social and mental health services to exonerees, as well as to advocate for comprehensive exoneree compensation through state statutes. PMID- 27180527 TI - Engaging Local Government through Neighborhoods and Communities. PMID- 27180529 TI - Confronting the Challenges in Using Social Network Sites for Cyber Youth Work. PMID- 27180528 TI - Writing Clearly for Clients: What Social Workers Should Know. PMID- 27180530 TI - In the Line of Duty: Racism in Health Care. PMID- 27180531 TI - Social Work and Pregnancy Discrimination. PMID- 27180532 TI - Social Work's Role in Ending the Criminalization of Homelessness: Opportunities for Action. PMID- 27180533 TI - Catching a Speeding Train: Social Work's Disconnect with a Medical Revolution. PMID- 27180534 TI - The 2016 Retirement Confidence Survey: Worker Confidence Stable, Retiree Confidence Continues to Increase. PMID- 27180558 TI - Editorial. PMID- 27180559 TI - Long-term follow-up of pediatric moyamoya disease treated by combined direct indirect revascularization surgery: single institute experience with surgical and perioperative management. AB - Moyamoya disease (MMD) is a rare occlusive cerebrovascular disease that mainly presents in children as cerebral ischemia. Prompt treatment with either a direct or indirect revascularization procedure is necessary for children with MMD in order to prevent repeated ischemic events. We herein present our experience with combined direct and indirect bypass surgery for the treatment of pediatric MMD as well as our uniquely designed perioperative protocol. Twenty-three patients with MMD, aged between 2 and 16 years old (mean 9.36), underwent 38 combined bypass procedures between 2008 and 2015. All patients underwent single superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis combined with encephalo-duro-myo-synangiosis (EDMS). The perioperative management protocol was stratified into two unique eras: the first era with normotensive care and the second era with strict blood pressure control (systolic 100-130 mmHg) and routine aspirin administration. Patients were followed after surgery for a period ranging between 3 and 131 months (mean 77 months) in yearly clinical and radiological follow-ups. Three postoperative complications were observed: two cases of cerebral hyperperfusion (2/38, 5.3 %) and one case of perioperative minor stroke (1/38, 2.6 %), two of which were in the first era. No strokes, either ischemic or hemorrhagic, were observed in the follow-up period, and the activity of daily living as shown by the modified Rankin Scale improved in 20 patients, with no deterioration being observed in any of our patients. STA-MCA bypass with EDMS is safe and effective for the management of pediatric MMD and provides long-term favorable outcomes. Perioperative care with blood pressure control combined with the administration of aspirin may reduce the potential risk of surgical complications. PMID- 27180561 TI - [Clinical and etiological profile malignant hypertension in children in pediatric intensive care]. AB - INTRODUCTION: Malignant hypertension (HTA), pediatrics, is unique by its clinical presentation, defined as severe hypertension accompanied by ischemic failure of one or more organs. METHODS-PATIENTS: Retroprospective study of cases of children admitted to pediatric intensive care. We chose a decline of 10 years from September 1994 to December 2004 for the first time, and from January 2005 to December 2015 for the second period; and we identified the cases presenting malignant hypertension (mHTA). RESULTS: Sixty-six patients were included, a prevalence of 0.6%. The age of patients ranged from 12months to 16years. The symptoms are related to the consequences of hypertension or condition in question. The most found signs are headache in more than 7%. Cerebrovascular event in 6%. A hypertensive convulsive encephalopathy 33.3% of patients. Renal disease is common, of varying severity. A fundus retinopathy was found in 47% stage 3, stage 4 in 51%. mHTA defined for the mean SBP values of 175mmHg and DBP average 112,5mmHg is often secondary to renal causes. The treatment is symptomatic with antihypertensive associated with the etiological treatment. Evolution is good out of 7 deaths. CONCLUSION: mHTA is a rare condition in the pediatric population. The clinical signs of functional rich under their impact on vital organs. The support must be early in intensive care. PMID- 27180560 TI - The role of brachytherapy in the treatment of glioblastoma multiforme. AB - Brachytherapy (BT) for glioblastoma multiforme (GBM) involves the use of radioactive isotopes to deliver ionizing radiation directly into the tumor bed. Its application as a means to prolong survival in GBM patients over the past few decades has come with variable success. The objective of this review is to describe the utility of BT in GBM, and to report the outcomes and adverse events associated with its use in different multimodal treatment approaches. A search of the literature was conducted using the PubMed database. The most recent search was performed in September 2015. Thirty-two series involving 1571 patients were included in our review. The longest median overall survival (MOS) following BT for newly diagnosed GBM reached 28.5 months. Overall, 1-, 2-, and 3-year survival rates were 46-89 %, 20-57 %, and 14-27 %. For recurrent GBM, the longest reported MOS after BT was 15.9 months. One-, 2- and 3-year survival rates for recurrent GBM were 10-66 %, 3-23 %, and 9-15 %. Adverse events were reported in 27 % of patients. Reoperation for radiation necrosis occurred in 4 and 27 % of patients following low- and high-dose rate BT, respectively. BT is a feasible option for extending survival in carefully selected GBM patients. As patient outcomes and overall survival improve with more aggressive radiotherapy, so does the risk of radiation-related complications. The most effective use of BT is likely as a part of multimodal treatment with other novel therapies. PMID- 27180562 TI - [Effects of an obesogenic diet enriched in sardine by-products on pro-atherogenic markers in Wistar rats]. AB - AIM OF THE STUDY: The effects of an obesogenic diet enriched in sardine by products (Sardina pilchardus) on blood pressure, glycemic control and some cardiovascular risk factors, in particular pro-atherogenic were studied on an experimental model. MATERIALS AND METHODS: Male rats (n=12) weighing 200+/-10g were subjected to an adjustment phase of 10 days in an obesogenic diet containing 30% sheep fat. After this period, the rats were divided into two homogeneous groups. The first group (HF-SBp) consumes the obesogenic diet supplemented with 30% of by-products flour (F-SBp), and the second (HF) continuous to consume the obesogenic diet and serve as control. RESULTS: At day 30, in HF-SBp versus HF group: a reduction was noted in diastolic (-11%) and systolic (-10%) pressure, glycemia (-19%), glycated hemoglobin percent (-43%), serum total lipids concentration (-22%), triacylglycerols (-37%), total cholesterol (-29%) and unesterified cholesterol (-30%), cholesteryl esters (-30%), cholesterol of very low density lipoprotein (-37%) and low density (-37%) was noted. Inversely, high density lipoprotein cholesterol and LCAT activity were enhanced by 19% and 77%, respectively. However, the atherogenicity index and membrane fluidity were reduced (P<0.05). CONCLUSION: Sardine by-products probably by their bioactive compounds properties seem to have antihypertensive, antidiabetic, hypolipidemic and antiatherogenic properties that could prevent and/or attenuate some metabolic disorders associated with obesity. PMID- 27180563 TI - [Cohort of renal infarction during 2years at Grenoble teaching hospital]. AB - BACKGROUND: Renal infarctions are rare events, clinical symptoms are various and diagnosis may be difficult, leading to diagnosis delay with kidney dysfunction risk. METHODS: During 24 months (March 2013-February 2015), all patients admitted in nephrology, cardiology, or internal medicine for renal infarction were recorded. Cardiovascular risk, clinic-biologic and radiologic data were recorded. A prospective follow-up at 6 months was offered for each patient. RESULTS: Eleven patients were admitted from emergency unit and 1 from general practitioner. Clinic symptoms are various: abdominal pain, headache, hypertension, and stroke. Diagnosis was not initially evocated, and was given by CT scan with 3 days median delay. Etiologies were composed of 5 dissections, 4 embolisms (atrial fibrillation), 1 cannabinoid arteritis, 1 thrombosis on atheroma, 1 thrombosis on postradiotherapy stenosis. Initial treatment was anticoagulation alone for 7 patients, with antiplatelet agent for 1 patient, anticoagulation followed by antiplatelet agent for 2 patients, and antiplatelet agent alone for 2 patients. We observed LDH elevation (4 cases on 5 available data) at admission; inflammatory syndrome, hypokalemia, and hypertension at 48-72h of symptoms. At 6months follow-up, one patient had altered glomerular filtration rate, and one patient had recidivism. CONCLUSION: Delay of diagnosis is a real problem for renal infarction, and need to be evocated every flank pain. LDH elevation may help clinician to suggest renal infarction and lead to CT scan. Association of delayed inflammatory syndrome, hypertension and hypokalemia after flank pain strongly suggest renal infarction. PMID- 27180564 TI - [P3S: Secured fitness trail set up in Guadeloupe, a tool to fight against physical inactivity: A device that has proved itself]. AB - OBJECTIVE: The objective is to introduce an original device already set up in Guadeloupe, the P3S: it is a secured fitness trail; it aims to raise awareness of the harmful effects of physical inactivity and to fight against physical inactivity. MATERIAL AND METHODS: The P3S device was financed by the Regional Council of Guadeloupe and includes: (1) a first space to perform a warm-up and gymnastics; (2) the route to the market; (3) 8 physical activity workshops. Coaching by educators sportsmen and teachers of activity physics adapted is proposed, provided by the ARS of Guadeloupe. Coordination is organized by the network of care, the HTA-GWAD network - Gip.Raspeg. RESULTS: A first evaluation of the device was conducted following the establishment on 10 routes drivers. The very encouraging results of these P3S led to extend the device to all communes of Guadeloupe who have at least a P3S. DISCUSSION: The proximity of these P3S, their free, and coaching provided by exercise teachers trained in sport health explains the success of these devices. CONCLUSION: The P3S are currently well known by the Guadeloupean population that well integrates this device. The supervision of educators is a source of motivation and makes P3S, a place where physical activities in group are practiced free of charge and in a friendly state of mind. This device might be known from other regions that could also set them up. PMID- 27180566 TI - [The use of echocardiography left ventricular filling pressures in hypertensive patients with heart failure and preserved systolic function in a North Africa unit day]. AB - OBJECTIVE: To assess the left ventricular (LV) filling pressures by Doppler Tissulaire Imaging (DTI) in the management of hypertensive patients with heart failure and preserved systolic function (HF-PEF) in our outpatient clinic. To involve the patient on the basis of their clinical, biological and echocardiography data, in identifying the risk factors that need change. PATIENTS AND METHODS: From 2004 to 2014, heart failure with preserved systolic function (HF-PEF) has been diagnosed in 200 consecutive hypertensive patients (pts) at our Algerian outpatient unit. Data were collected on blood pressure at the time of the examination, body mass index (BMI), waist, comorbid conditions including dyslipidemia, diabetes and atrial fibrillation (AF). LV ejection fraction>50 % is taken as the including criteria with acquisition as described in the Chamber Quantification update. Left ventricular global systolic function by biplane disk summation Simpson method and diastolic function is assessed by the mitral inflow measurements regarding recommendations for the evaluation of left ventricular diastolic function by echocardiography from the European Association of Cardiovascular Imaging (EACVI) and the American Society of Echocardiography (ASE). RESULTS: Mean age was 65+/-11 yrs; 66 % were female; waist circumference in men>102cm and in women>88cm was found in 82 % of the pts and 50 % were diabetics. Body weight (BMI)>30kg/m(2) is depicted in 88 (44 %). Dyslipidemia is depicted in 78 pts (39 %). Ischemic heart disease was diagnosed in 64 pts (32 %); history of thromboembolic event in 78 pts (39 %); valvular disease in 40 pts (20 %). ECG showed AF in 60 pts (30 %), complete left bundle branch block (LBBB) in 20 pts (10 %). The echographic findings were as follow: left ventricular hypertrophy (LVH) in 126 pts (63 %) and left atrial (LA) enlargement in 111 pts (55 %). Mean left ventricular ejection fraction (LVEF) is about 55+/-10 %. Delayed relaxation (Em/Am<1) and deceleration time>150ms (DT) in 80 pts (40 %), of them, 56 had increased filling pressures (Em/Ea>8 and Ap>Am); pseudo-normal patterns (1=2) and short DT<100ms in 40 pts (20 %). CONCLUSIONS: The hypertensive pts referred for an echo examination are often diabetics and frequently demonstrate preserved left ventricular function with increased filling pressures. This is useful for managing their treatments in the context of a cardiac rehabilitation programme. PMID- 27180565 TI - [Medication reconciliation at hospital discharge focusing on patient with hypertension: Analysis of the output prescription]. AB - PURPOSE: To describe pharmacists' interventions made at patients hospital discharge from Department of Hypertension. METHODS: This is a single-center and prospective study over an 8-week period. At hospital discharge, the pharmacist compared pre-admission and inpatient medications with discharge orders and written instructions. Pharmacists' interventions were then classified in 4 categories. All variances and discrepancies were discussed with the prescribing physician when possible. RESULTS: Over the 8-week period, 154 cases were analyzed. Pharmacists' interventions at discharge underwent 48 times on 21% of the patients (n=33) but none was clinically relevant. Among these 48 cases, 40% (n=19) were rated as "inappropriate administration", 27% (n=13) were classified as "incomplete prescription", 19% (n=9) were "variances" and 4% (n=2) were due to "omission prescription". In 10% of the cases (n=5), discrepancies appeared without any possible further analysis as no discussion with the prescriber occurred. CONCLUSION: One fifth of all patients analyzed was the subject of a pharmacists' intervention. The complementary action of the pharmacist improves the consistency of the prescriptions and strengthens patient safety. PMID- 27180568 TI - [Effect of N-3 polyunsaturated fatty acids on the modulation of T lymphocytes in vitro and redox status in obese women with hypertension]. AB - OBJECTIVES: Deepen our knowledge of the immune system alterations associated with obesity-related hypertension and demonstrate that polyunsaturated fatty acids can enhance the proliferation and their profile oxidant/antioxidant and subsequently involved in the strategy prevention and treatment in obese hypertensives. METHODS: T cells are isolated from the blood of the control and obese women with hypertension the University Hospital of Tlemcen (Algeria), these cells are incubated in the presence of a synthetic mixture of PUFA to 30MUM (DHA/EPA/LA) and stimulated by mitogens for 48hours. The cells are counted and used to assess intracellular oxidative status. The biochemical parameters are determined by the use of plasma. RESULTS: In obese women with hypertension, a significant increase in plasma levels of (glucose, uric acid, creatinine, urea, total cholesterol and triglycerides) compared to controls. In addition, decreased cell proliferation, basal or stimulated by Con A was observed in obese women with hypertension compared with controls. The mixture of PUFA to 30MUM reduced lymphoproliferation as well in obese women with hypertension than in controls. The rates in malondialdehyde (MDA) and protein carbonyl lymphocytes are elevated in hypertensive obese women. PUFA supplementation to 30MUM seems correct this redox status in hypertensive obese since rates in protein carbonyl, are similar to those of controls. CONCLUSION: The mixture of PUFA (n-3 and n-6) can modulate the activity of T lymphocyte proliferation and correct the intracellular redox status in hypertensive obese women. PMID- 27180567 TI - [Prevalence of true resistant hypertension among uncontrolled hypertensive patients referred to a tertiary health care center]. AB - OBJECTIVES: Estimate the prevalence of resistant hypertension (rHTN) in uncontrolled hypertensive treated patients referred to a tertiary care center specialized for hypertension management. METHODS: The study was prospective observational. Between January 2013 and April 2015, we recruited hypertensive treated patients, 18years age or older, under antihypertensive drugs since at least 12months, and referred to the hypertension unit of Tizi-ouzou university hospital for uncontrolled hypertension. rHTn was defined as an office blood pressure>=140mmHg despite a triple therapy including renin angiotensin system blockers, calcium antagonists and diuretics at optimal doses, since at least 4weeks. RESULTS: We screened 2367 patients with a mean age of 61.1+/-11.2years and 64.2% of men. Eight hundred forty-three (35.6%) patients had suboptimal treatment, 364 (15.4%) a poor adherence to treatment and 202 (8.5%) a white-coat effect. An excessive salt intake and a drug-related hypertension were identified in 281 (11.9%) and 36 (1.5%) patients, respectively. A secondary cause of hypertension was diagnosed in 468 (19.8%) subjects. Finally, only 173 patients showed a true rHTN requiring four drugs or more and its prevalence was 7.3% (CI 95%: 6.3-8.3). CONCLUSION: Less than one patient from ten referred in our center for uncontrolled hypertension had a true rHTN, and more than fifty percent of patients had pseudo-resistance. Most of patients with seemingly rHTN can reach blood pressure target provided they undergo thorough work up and care by a specialized team. PMID- 27180569 TI - Inflammatory Responses in a Benign Prostatic Hyperplasia Epithelial Cell Line (BPH-1) Infected with Trichomonas vaginalis. AB - Trichomonas vaginalis causes the most prevalent sexually transmitted infection worldwide. Trichomonads have been detected in prostatic tissues from prostatitis, benign prostatic hyperplasia (BPH), and prostate cancer. Chronic prostatic inflammation is known as a risk factor for prostate enlargement, benign prostatic hyperplasia symptoms, and acute urinary retention. Our aim was to investigate whether T. vaginalis could induce inflammatory responses in cells of a benign prostatic hyperplasia epithelial cell line (BPH-1). When BPH-1 cells were infected with T. vaginalis, the protein and mRNA of inflammatory cytokines, such as CXCL8, CCL2, IL-1beta, and IL-6, were increased. The activities of TLR4, ROS, MAPK, JAK2/STAT3, and NF-kappaB were also increased, whereas inhibitors of ROS, MAPK, PI3K, NF-kappaB, and anti-TLR4 antibody decreased the production of the 4 cytokines although the extent of inhibition differed. However, a JAK2 inhibitor inhibited only IL-6 production. Culture supernatants of the BPH-1 cells that had been incubated with live T. vaginalis (trichomonad-conditioned medium, TCM) contained the 4 cytokines and induced the migration of human monocytes (THP-1 cells) and mast cells (HMC-1 cells). TCM conditioned by BPH-1 cells pretreated with NF-kappaB inhibitor showed decreased levels of cytokines and induced less migration. Therefore, it is suggested that these cytokines are involved in migration of inflammatory cells. These results suggest that T. vaginalis infection of BPH patients may cause inflammation, which may induce lower urinary tract symptoms (LUTS). PMID- 27180570 TI - Identification of Protein Arginine Methyltransferase 5 as a Regulator for Encystation of Acanthamoeba. AB - Encystation is an essential process for Acanthamoeba survival under nutrient limiting conditions and exposure to drugs. The expression of several genes has been observed to increase or decrease during encystation. Epigenetic processes involved in regulation of gene expression have been shown to play a role in several pathogenic parasites. In the present study, we identified the protein arginine methyltransferase 5 (PRMT5), a known epigenetic regulator, in Acanthamoeba castellanii. PRMT5 of A. castellanii (AcPRMT5) contained domains found in S-adenosylmethionine-dependent methyltransferases and in PRMT5 arginine N-methyltransferase. Expression levels of AcPRMT5 were increased during encystation of A. castellanii. The EGFP-PRMT5 fusion protein was mainly localized in the nucleus of trophozoites. A. castellanii transfected with siRNA designed against AcPRMT5 failed to form mature cysts. The findings of this study lead to a better understanding of epigenetic mechanisms behind the regulation of encystation in cyst-forming pathogenic protozoa. PMID- 27180571 TI - Sterculic Acid and Its Analogues Are Potent Inhibitors of Toxoplasma gondii. AB - Toxoplasmosis is a serious disease caused by Toxoplasma gondii, one of the most widespread parasites in the world. Lipid metabolism is important in the intracellular stage of T. gondii. Stearoyl-CoA desaturase (SCD), a key enzyme for the synthesis of unsaturated fatty acid is predicted to exist in T. gondii. Sterculic acid has been shown to specifically inhibit SCD activity. Here, we examined whether sterculic acid and its methyl ester analogues exhibit anti-T. gondii effects in vitro. T. gondii-infected Vero cells were disintegrated at 36 hr because of the propagation and egress of intracellular tachyzoites. All test compounds inhibited tachyzoite propagation and egress, reducing the number of ruptured Vero cells by the parasites. Sterculic acid and the methyl esters also inhibited replication of intracellular tachyzoites in HFF cells. Among the test compounds, sterculic acid showed the most potent activity against T. gondii, with an EC50 value of 36.2 MUM, compared with EC50 values of 248-428 MUM for the methyl esters. Our study demonstrated that sterculic acid and its analogues are effective in inhibition of T. gondii growth in vitro, suggesting that these compounds or analogues targeting SCD could be effective agents for the treatment of toxoplasmosis. PMID- 27180572 TI - Exosomes Secreted by Toxoplasma gondii-Infected L6 Cells: Their Effects on Host Cell Proliferation and Cell Cycle Changes. AB - Toxoplasma gondii infection induces alteration of the host cell cycle and cell proliferation. These changes are not only seen in directly invaded host cells but also in neighboring cells. We tried to identify whether this alteration can be mediated by exosomes secreted by T. gondii-infected host cells. L6 cells, a rat myoblast cell line, and RH strain of T. gondii were selected for this study. L6 cells were infected with or without T. gondii to isolate exosomes. The cellular growth patterns were identified by cell counting with trypan blue under confocal microscopy, and cell cycle changes were investigated by flow cytometry. L6 cells infected with T. gondii showed decreased proliferation compared to uninfected L6 cells and revealed a tendency to stay at S or G2/M cell phase. The treatment of exosomes isolated from T. gondii-infected cells showed attenuation of cell proliferation and slight enhancement of S phase in L6 cells. The cell cycle alteration was not as obvious as reduction of the cell proliferation by the exosome treatment. These changes were transient and disappeared at 48 hr after the exosome treatment. Microarray analysis and web-based tools indicated that various exosomal miRNAs were crucial for the regulation of target genes related to cell proliferation. Collectively, our study demonstrated that the exosomes originating from T. gondii could change the host cell proliferation and alter the host cell cycle. PMID- 27180573 TI - In Vitro and in Vivo Effects of Nitrofurantoin on Experimental Toxoplasmosis. AB - Toxoplasma gondii is an important opportunistic pathogen that causes toxoplasmosis, which has very few therapeutic treatment options. The most effective therapy is a combination of pyrimethamine and sulfadiazine; however, their utility is limited because of drug toxicity and serious side effects. For these reasons, new drugs with lower toxicity are urgently needed. In this study, the compound, (Z)-1-[(5-nitrofuran-2-yl)methyleneamino]-imidazolidine-2,4-dione (nitrofurantoin), showed anti-T. gondii effects in vitro and in vivo. In HeLa cells, the selectivity of nitrofurantoin was 2.3, which was greater than that of pyrimethamine (0.9). In T. gondii-infected female ICR mice, the inhibition rate of T. gondii growth in the peritoneal cavity was 44.7% compared to the negative control group after 4-day treatment with 100 mg/kg of nitrofurantoin. In addition, hematology indicators showed that T. gondii infection-induced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, biochemical parameters involved in liver injury, were reduced by nitrofurantoin significantly. Moreover, nitrofurantoin exerted significant effects on the index of antioxidant status, i.e., malondialdehyde (MDA) and glutathione (GSH). The nitrofurantoin-treated group inhibited the T. gondii-induced MDA levels while alleviating the decrease in GSH levels. Thus, nitrofurantoin is a potential anti T. gondii candidate for clinical application. PMID- 27180574 TI - Activation and Recruitment of Regulatory T Cells via Chemokine Receptor Activation in Trichinella spiralis-Infected Mice. AB - As most infections by the helminth parasite elicit the recruitment of CD4(+)CD25(+)Foxp3(+) T (Treg) cells, many scientists have suggested that these cells could be used for the treatment of immune-mediated inflammation and associated diseases. In order to investigate the distribution and alteration of activated Treg cells, we compared the expression levels of Treg cell activation markers in the ileum and gastrocnemius tissues 1, 2, and 4 weeks after infection. The number of Treg cells was monitored using GFP-coded Foxp3 transgenic mice. In mice at 1 week after Trichinella spiralis infection, the number of activated Treg cells was higher than in the control group. In mice at 2 weeks after infection, there was a significant increase in the number of cells expressing Foxp3 and CTLA 4 when compared to the control group and mice at 1 week after infection. At 4 weeks after infection, T. spiralis was easily identifiable in nurse cells in mouse muscles. In the intestine, the expression of Gzmb and Klrg1 decreased over time and that of Capg remained unchanged for the first and second week, then decreased in the 4th week. However, in the muscles, the expression of most chemokine genes was increased due to T. spiralis infection, in particular the expression levels of Gzmb, OX40, and CTLA-4 increased until week 4. In addition, increased gene expression of all chemokine receptors in muscle, CXCR3, CCR4, CCR5, CCR9, and CCR10, was observed up until the 4th week. In conclusion, various chemokine receptors showed increased expressions combined with recruitment of Treg cells in the muscle tissue. PMID- 27180575 TI - Complete Mitochondrial Genome of Echinostoma hortense (Digenea: Echinostomatidae). AB - Echinostoma hortense (Digenea: Echinostomatidae) is one of the intestinal flukes with medical importance in humans. However, the mitochondrial (mt) genome of this fluke has not been known yet. The present study has determined the complete mt genome sequences of E. hortense and assessed the phylogenetic relationships with other digenean species for which the complete mt genome sequences are available in GenBank using concatenated amino acid sequences inferred from 12 protein coding genes. The mt genome of E. hortense contained 12 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and 1 non-coding region. The length of the mt genome of E. hortense was 14,994 bp, which was somewhat smaller than those of other trematode species. Phylogenetic analyses based on concatenated nucleotide sequence datasets for all 12 protein-coding genes using maximum parsimony (MP) method showed that E. hortense and Hypoderaeum conoideum gathered together, and they were closer to each other than to Fasciolidae and other echinostomatid trematodes. The availability of the complete mt genome sequences of E. hortense provides important genetic markers for diagnostics, population genetics, and evolutionary studies of digeneans. PMID- 27180576 TI - Genetic Identification of Spirometra decipiens Plerocercoids in Terrestrial Snakes from Korea and China. AB - Human sparganosis is a zoonotic disease caused by infection with larval forms (procercoid/plerocercoid) of Spirometra spp. The purpose of this study was to identify Spirometra spp. of infected snakes using a multiplex PCR assay and phylogenetic analysis of mitochondrial DNA sequence data from the spargana of terrestrial snakes obtained from Korea and China. A total of 283 snakes were obtained that included 4 species of Colubridae comprising Rhabdophis tigrinus tigrinus (n=150), Dinodon rufozonatum rufozonatum (n=64), Elaphe davidi (n=2), and Elaphe schrenkii (n=7), and 1 species of Viperidae, Agkistrodon saxatilis (n=60). The snakes were collected from the provinces of Chungbuk, Chungnam, and Gyeongbuk in Korea (n=161), and from China (n=122). The overall infection rate with spargana was 83% (235/283). The highest was recorded for D. rufozonatum rufozonatum (100%), followed by A. saxatilis (85%) and R. tigrinus tigrinus (80%), with a negative result for E. davidi (0%) and E. schrenkii (0%). The sequence identities between the spargana from snakes (n=50) and Spirometra erinaceieuropaei (KJ599680) or S. decipiens (KJ599679) control specimens were 90.8% and 99.2%, respectively. Pairwise genetic distances between spargana (n=50) and S. decipiens ranged from 0.0080 to 0.0107, while those between spargana and S. erinaceieuropaei ranged from 0.1070 to 0.1096. In this study, all of the 904 spargana analyzed were identified as S. decipiens either by a multiplex PCR assay (n=854) or mitochondrial cox1 sequence analysis (n=50). PMID- 27180577 TI - Prevalence of Trichomoniasis by PCR in Women Attending Health Screening in Korea. AB - Trichomoniasis is the most common curable sexually-transmitted infection (STI) worldwide. There are few reports on the prevalence of Trichomonas vaginalis in Korea. The purpose of this study was to examine the prevalence of trichomoniasis by PCR in Guri city, Korea. All adult women who visited Hanyang University Guri Hospital for health screening within the National Health Care Service were invited to participate in the study, and 424 women were enrolled between March and June 2011. PCR was used to detect Trichomonas vaginalis using primers based on a repetitive sequence cloned from T. vaginalis (TV-E650). Fourteen women (3.3%) were found to have T. vaginalis. All were over 50, and they were significantly older on average than the 410 Trichomonas-negative women (mean ages 63.4 vs 55.3 years). It seems that T. vaginalis infection is not rare in women receiving health screening, especially among those over 50. PMID- 27180578 TI - Optimization of Trichomonas vaginalis Diagnosis during Pregnancy at a University Hospital, Argentina. AB - The aim of this study was to evaluate different methods for Trichomonas vaginalis diagnosis during pregnancy in order to prevent maternal and perinatal complications. A total of 386 vaginal exudates from pregnant women were analyzed. T. vaginalis was investigated by 3 types of microscopic examinations direct wet mount with physiologic saline solution, prolonged May-Grunwald Giemsa (MGG) staining, and wet mount with sodium-acetate-formalin (SAF)/methylene blue method. PCR for 18S rRNA gene as well as culture in liquid medium were performed. The sensitivity and specificity of the microscopic examinations were evaluated considering the culture media positivity or the PCR techniques as gold standard. The frequency of T. vaginalis infection was 6.2% by culture and/or PCR, 5.2% by PCR, 4.7% by culture, 3.1% by SAF/methylene blue method and 2.8% by direct wet smear and prolonged MGG staining. The sensitivities were 83.3%, 75.0%, 50.0%, and 45.8% for PCR, culture, SAF/methylene blue method, and direct wet smear-prolonged MGG staining, respectively. The specificity was 100% for all the assessed methods. Microscopic examinations showed low sensitivity, mainly in asymptomatic pregnant patients. It is necessary to improve the detection of T. vaginalis using combined methods providing higher sensitivity, such as culture and PCR, mainly in asymptomatic pregnant patients, in order to prevent maternal and perinatal complications. PMID- 27180579 TI - Identification of Cryptosporidium from Dairy Cattle in Pahang, Malaysia. AB - Cryptosporidium, a protozoan parasite, can cause cryptosporidiosis which is a gastrointestinal disease that can infect humans and livestock. Cattle are the most common livestock that can be infected with this protozoan. This study was carried out to determine the prevalence of Cryptosporidium infection in cattle in Kuantan, Pahang, Malaysia and to find out the association between the occurrence of infection and 3 different ages of cattle (calves less than 1 year, yearling, and adult cattle). The samples were processed by using formol-ether concentration technique and stained by modified Ziehl Neelsen. The results showed that 15.9% (24/151) of cattle were positive for Cryptosporidium oocysts. The occurrence of Cryptosporidium in calves less than 1 year was the highest with the percentage of 20.0% (11/55) followed by yearling and adult cattle, with the percentage occurrence of 15.6 % (7/45) and 11.8% (6/51), respectively. There was no significant association between the occurrence and age of cattle and presence of diarrhea. Good management practices and proper hygiene management must be taken in order to reduce the infection. It is highly important to control the infection since infected cattle may serve as potential reservoirs of the infection to other animals and humans, especially animal handlers. PMID- 27180581 TI - Three Nematode Species Recovered from Terrestrial Snakes in Republic of Korea. AB - The majority of parasitological studies of terrestrial snakes in Korea have focused on zoonotic parasites. However, in the present study, we describe 3 unrecorded nematode species recovered from 5 species of snakes (n=6) in Korea. The examined snakes, all confiscated from illegal hunters, were donated by the Chungnam Wild Animal Rescue Center and Korean Broadcasting System in July 2014 and February 2015. Light and scanning electron microscopies on the shapes of spicules that are either bent or straight (kalicephalids) and the presence of the intestinal cecum (ophidascarids) figured out 3 nematodes; Kalicephalus brachycephalus Maplestone, 1931, Kalicephalus sinensis Hsu, 1934, and Ophidascaris excavata Hsu and Hoeppli, 1934. These 3 species of nematode faunas are recorded for the first time in Korea. PMID- 27180580 TI - High Toxoplasma gondii Seropositivity among Brain Tumor Patients in Korea. AB - Toxoplasma gondii is an intracellular protozoan that can modulate the environment of the infected host. An unfavorable environment modulated by T. gondii in the brain includes tumor microenvironment. Literature has suggested that T. gondii infection is associated with development of brain tumors. However, in Korea, epidemiological data regarding this correlation have been scarce. In this study, in order to investigate the relationship between T. gondii infection and brain tumor development, we investigated the seroprevalence of T. gondii among 93 confirmed brain tumor patients (various histological types, including meningioma and astrocytoma) in Korea using ELISA. The results revealed that T. gondii seropositivity among brain tumor patients (18.3%) was significantly (P<0.05) higher compared with that of healthy controls (8.6%). The seropositivity of brain tumor patients showed a significant age-tendency, i.e., higher in younger age group, compared with age-matched healthy controls (P<0.05). In conclusion, this study supports the close relationship between T. gondii infection and incidence of brain tumors. PMID- 27180582 TI - Prevalence of Clonorchis sinensis Infection among Residents along 5 Major Rivers in the Republic of Korea. AB - Clonorchis sinensis is currently the most important parasite affecting public health problems in the Republic of Korea. We investigated the prevalence of C. sinensis infection among residents living along 5 major rivers in Korea. A total of 42,562 individual stool samples were collected from 37 localities and examined using the formalin-ether sedimentation technique. Helminth eggs were detected in 4,052 (9.5%) residents and 3,586 (8.4%) were infected with C. sinensis. The egg positive rate of C. sinensis in Nakdong, Seomjin, Geum, Yeongsan, and Han River was 11.7%, 9.9%, 6.5%, 3.1%, and 1.0%, respectively. The overall prevalence of clonorchiasis by sex was 11.2% in males and 6.2% in females. The age-prevalence was the highest in the 50-59 years band. It has been reconfirmed that the endemicity of clonorchiasis is higher in southern areas of Korea, especially along Nakdong and Seomjin Rivers. A combination of continuous control programs with health education initiatives is urgently required in these highly endemic areas of clonorchiasis in Korea. PMID- 27180583 TI - Plerocercoids of Nybelinia surmenicola (Cestoda: Tentacularidae) in Squids, Todarodes pacificus, from East Sea, the Republic of Korea. AB - A visceral helminth of the squid, Todarodes pacificus, is reported from the East Sea, the Republic of Korea. Total 39 squid samples were purchased from a fish market in Jumunjin-eup, Gangneung-si (City) from August 2014 to July 2015 and were examined for helminth parasites with naked eyes and under a stereomicroscope after opening the abdominal cavity with a pair of scissors. Whitish larval worms were mainly found in the stomach and abdominal cavity of the squid. They were detected in 25 (64.1%) out of 39 squids examined, and the infection density was 7 larvae per infected squid. Spatula-shaped larvae were 8.2*2.0 mm in average size, round to slightly flattened anteriorly, with round hatching posteriorly, and had characteristic 4 tentacles with numerous hooklets in the scolex. The larvae were identified as the plerocercoid stage of Nybelinia surmenicola by their morphological features. This finding represents a new host record and the first report of N. surmenicola infection in T. pacificus squids from the east coast of Korea. PMID- 27180585 TI - Ornithodoros sawaii (Ixodida: Argasidae) Larvae Collected from Hydrobates monorhis on Sogugul and Gaerin Islands, Jeollanam-do (Province), Republic of Korea. AB - The 65th Medical Brigade and Public Health Command District-Korea, in collaboration with the Migratory Bird Research Center, National Park Research Institute, conducted migratory bird tick surveillance at Sogugul and Gaerin Islands (small rocky bird nesting sites), Jeollanam-do (Province), Republic of Korea (ROK), on 30 July and 1 August 2009. Breeding seabirds captured by hands in their nesting burrows were banded, identified to species, and carefully examined for ticks during the nesting season. A total of 9 Ornithodoros sawaii larvae were removed from 4 adult Hydrobates monorhis (Swinhoe's storm petrel). The identification of the larvae of O. sawaii collected from migratory seabirds were molecularly confirmed using mitochondrial 16S rDNA primer sets. PMID- 27180584 TI - A Rapid and Convenient Method for in Vivo Fluorescent Imaging of Protoscolices of Echinococcus multilocularis. AB - Human and animal alveolar echinococcosis (AE) are important helminth infections endemic in wide areas of the Northern hemisphere. Monitoring Echinococcus multilocularis viability and spread using real-time fluorescent imaging in vivo provides a fast method to evaluate the load of parasite. Here, we generated a kind of fluorescent protoscolices in vivo imaging model and utilized this model to assess the activity against E. multilocularis protoscolices of metformin (Met). Results indicated that JC-1 tagged E. multilocularis can be reliably and confidently used to monitor protoscolices in vitro and in vivo. The availability of this transient in vivo fluorescent imaging of E. multilocularis protoscolices constitutes an important step toward the long term bio-imaging research of the AE infected mouse models. In addition, this will be of great interest for further research on infection strategies and development of drugs and vaccines against E. multilocularis and other cestodes. PMID- 27180586 TI - Western Blot Detection of Human Anti-Chikungunya Virus Antibody with Recombinant Envelope 2 Protein. AB - Chikungunya virus (CHIKV), a tropical pathogen, has re-emerged and has massive outbreaks abruptly all over the world. Containing many dominant epitopes, the envelope E2 protein of CHIKV has been explored for the vaccination or diagnosis. In the present study, the antigenicity of a recombinant expressed intrinsically disorder domain (IUD) of E2 was tested for the detection of the antibody against CHIKV through western blot method. The gene of the IUD of E2 was inserted into 2 different vectors and expressed as recombinant GST-E2 and recombinant MBP-E2 fusion protein, respectively. Two kinds of fusion proteins were tested with 30 CHIKV patient sera and 30 normal sera, respectively. Both proteins were detected by 25 patients sera (83.3%) and 1 normal serum (3.3%). This test showed a relatively high sensitivity and very high specificity of the recombinant E2 proteins to be used as diagnostic antigens against CHIKV infection. PMID- 27180587 TI - Standardized grossing protocol is useful for the pathology reporting of malignant neoplasms other than adenocarcinomas treated with pancreaticoduodenectomy. AB - BACKGROUND: There is no universally accepted protocol for gross examination of pancreaticoduodenectomy specimens. Standardized protocol (SP), known as Leeds Pathology Protocol, was previously validated in pancreatic adenocarcinoma. In this study we aimed to assess usefulness of SP in a series of specimens with pancreatic, ampullary, and duodenal malignant neoplasms other than adenocarcinomas. MATERIALS AND METHODS: SP was based on multi-colour inking and serial slicing of the specimens in a plane perpendicular to the duodenal axis. SP was used in a prospective cohort of 35 neoplasms of neuroendocrine, acinar, and solid-pseudopapillary lineage (SP cohort). Surgical margin status, primary tumour stage, and lymph node yield in SP group were compared with corresponding data of a historical cohort of 19 cases examined using non-standardized protocol (NSP). Samples examined in NSP and SP cohorts were comparable in terms of basic clinical characteristics, median tumour diameter, and distribution of histopathological diagnostic categories. RESULTS: In SP cohort we noticed: (1) higher rate of detection of tumour tissue at surgical margins, (2) more frequent peripancreatic fat tissue invasion, (3) higher percentage of perineural invasion, (4) larger number of lymph nodes retrieved from the specimen, in comparison to NSP group. Application of SP was associated with significantly higher number of tissue blocks taken for histology. CONCLUSIONS: SP can be successfully applied for macroscopical examination of pancreaticoduodenectomy specimens with malignant pancreatic, ampullary, and duodenal neoplasms other than adenocarcinomas. SP with proper microscopical diagnosis enables an appropriate schedule of patients with these neoplasms to adjuvant therapy and surveillance programmes. PMID- 27180588 TI - [Chinese cough guidelines go further on the path of evidence-based medicine]. PMID- 27180589 TI - [Validation of the Chinese version of Hull airway reflux questionnaire and its application in the evaluation of chronic cough]. AB - OBJECTIVE: To validate the effectiveness, repeatability and treatment responsiveness of the Chinese version of Hull airway reflux questionnaire (HARQ), and to determine its clinical value. METHODS: A standard Chinese version of HARQ was developed by an established translation procedure and its repeatability was assessed in a preliminary study involving 55 untreated patients with stable chronic cough. Thereafter, a total of 132 patients with chronic cough referred to our respiratory clinic were recruited into the study between May 2014 and April 2015. After their cough was evaluated with the HARQ, cough symptom score or cough reflex sensitivity to inhaled capsaicin and the correlations among them were analyzed, and the causes of chronic cough in all the patients were presumptively determined according to an established diagnostic protocol and finally confirmed with the subsequent therapy specific to the etiologies. After two weeks of effective treatment, HARQ, cough symptom score and cough reflex sensitivity to inhaled capsaicin were measured once more, and treatment responsiveness was calculated. The score of the HARQ in 132 patients with chronic cough were compared with that in 104 healthy volunteers. RESULTS: The repeatability of the Chinese version of the HARQ was validated at a week interval with the intraclass correlation coefficients of 0.96 (95%CI: 0.93-0.98, P=0.00) for total score (n=55). No correlation was found between the HARQ and cough symptom score, and the HARQ showed a weak negative correlation with cough threshold C2 (rIgC2=-0.23, P=0.01) but not with C5. The value of HARQ was significantly higher in patients with chronic cough than in healthy volunteers[20.00(14.00, 28.00) vs 4.00 (2.00, 6.00), Z=-12.89, P=0.00], but no difference of HARQ in gender or age existed in chronic cough. Although all the patients with various etiologies of chronic cough had an increased value of HARQ, cough due to gastroesophageal reflux showed the highest HARQ score among them[28.50 (25.00, 32.25) vs 18.50 (14.00, 26.25), Z=4.43, P=0.00]. After two weeks of effective treatment, the HARQ score decreased from 20.00 (14.00, 28.00) pre-treatment to 10.00 (4.25, 17.75) post-treatment (Z= 6.06, P=0.00), with 52.04% of score change ratio, 1.38 of effect side and 1.97 of standard response mean respectively. CONCLUSION: HARQ is a reliable and valid tool for the management of chronic cough with good treatment responsiveness, and may be used as an easy way to predict cough due to gastroesophageal reflux. PMID- 27180590 TI - [The distribution characteristics of etiology of chronic cough in Lanzhou]. AB - OBJECTIVE: To explore the distribution characteristics of etiology and clinical feature of chronic cough in Lanzhou. METHODS: Based on the guidelines of the diagnostic process of chronic cough in China, data of medical history and physical examinations were collected, and chest X-ray, pulmonary function plus airway hyperresponsiveness, induced sputum eosinophils, sinus X-ray or CT, 24 h esophageal pH monitoring, chest high-resolution CT and bronchoscopy were performed accordingly for outpatients with chronic cough. The cause of chronic cough was identified by the test results and treatment response. The results were compared with those reported previously in other areas of China. RESULTS: A total of 173 patients with completed data were collected, including 90 males and 83 females.The causes were as follows: 45 cases (26.01%) of cough variant asthma, 35 (20.23%) upper airway cough syndrome, 20 (11.56%) allergic cough, 17 (9.83%) chronic pharyngitis, 14 (8.09%) gastroesophageal reflux, 14 (8.09%)postinfectious, 13 (7.51%) eosinophilic bronchitis, 8 (4.62%) chronic bronchitis, 4 (2.31%) cough associated with ACEI, 3 (1.73%) bronchial tuberculosis, 2 (1.16%) pulmonary fibrosis and bronchiectasis repectively. The causes of the remaining 14 patients (8.09%)were unknown. The causes of chronic cough were identified in 159 patients (91.91%), of which 141 (88.68%) with a single cause and 18(11.32%)with more than 2 etiological factors.The percentage of cough variant asthma in our series was significantly higher than that reported in Guangzhou (13.6%, chi(2)=5.60, P=0.018, P<0.05), but lower than that reported in Shenyang (39.4%, chi(2)=7.91, P=0, 004, P<0.01). The percentage of allergic cough was higher than that reported in Beijing (3.3%, chi(2)=6.66, P=0.010, P<0.05), and that of eosinophilic bronchitis was lower than those reported in Guangzhou(22.4%, chi(2)=22.38, P=0.000, P<0.01) and Shenyang (12.5%, chi(2)=8.09, P=0.005, P<0.01). The percentage of esophageal reflux cough was lower than that reported in Beijing (20.3%, chi(2)=9.40, P=0.002, P<0.01) but higher than that reported in Shenyang (1.9%, chi(2)=3.98, P=0.036, P<0.05). CONCLUSION: In Lanzhou, cough variant asthma, upper airway cough syndrome, allergic cough, chronic pharyngitis and gastroesophageal reflux were the main causes of chronic cough, and the etiological distribution was different from Guangzhou, Beijing, Shenyang and other areas. PMID- 27180591 TI - [Incidence, bacterial spectrum and predictive risk factors for stent associated respiratory tract infection]. AB - OBJECTIVE: To evaluate the incidence, bacterial spectrum and predictive risk factors for stent associated respiratory tract infection (SARTI). METHODS: A prospective nested case-control study was conducted to evaluate the incidence of SARTI and the predictive risk factors for SARTI. Respiratory symptoms, sputum bacterial culture, electronic bronchoscopy investigation, bacterial culture obtained from protective bronchoscopic brushing, and chest radiographs were evaluated before and after stent implantation. RESULTS: (1) Between January, 2011 and March, 2015, a total of 103 patients were included. The incidence of SARTI was 27.2% (28/103). (2) The incidence of SARTI was similar in subgroups with different stent types (metal stent or silicon stent) and different stent shapes (straight, L or Y shape). (3)Staphylococcus aureus (50.0%, 14/28) and Pseudomonas aeruginosa (35.7%, 10/28) were the dominant pathogens. The infection of Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans occurred 7 (4 60) days, 53 (15-67) days and 63 (28-90) days after stent implantation, respectively. (4) Binary logistical regression model analysis showed that female gender(OR=0.178, P=0.011) and age below 50 years (OR=3.91, P=0.036) were favorable predictive risk factors for SARTI. CONCLUSIONS: SARTI occurs in a quarter of the patients. Staphylococcus aureus and Pseudomonas aeruginosa are the dominant pathogens. Female gender and younger age are favorable predictive factors for SARTI. PMID- 27180592 TI - [Analysis on the polymorphisms of human B cell epitopes of 5 specificity antigens in Mycobacterium tuberculosis in China]. AB - OBJECTIVE: To study the diversities of human B cell epitopes of five proteins (Mpt83, Mpt70, LpqH, PstS3, GroES) in Mycobacterium tuberculosis isolates from China. METHODS: We selected 179 strains isolated from patients with tuberculosis in different regions of China, and cultured these strains by L-J medium. The gene sequences of these 5 proteins were amplified and sequenced by PCR. The variations (single nucleotide polymorphisms, SNP) of the DNA sequences were compared and analyzed according to the immune epitope database (IEDB). The synonymous mutation rate (dS), non-synonymous mutation rate (dN) and dN/dS values were calculated with MEGA6 software. RESULTS: Among the 179 clinical MTBC isolates, 7 SNP mutations were found in the mpt83gene. The dN/dS value of the whole mpt83 gene was 0.88. One SNP mutation was found in the mpt70 gene. The dN/dS values of the whole pstS3 gene and non-B epitopes areas were 1.74 and 1.40 respectively. But no mutation was found in the groES gene. CONCLUSION: The mpt83, lpqH and pstS3 genes of 179 MTBC strains contain gene SNPs and human B cell epitopes diversities, while the coding gene and human B cell epitopes of protein mpt70 and groES were conservative. PMID- 27180593 TI - [The effect of phospholipid transfer protein on cigarette smoke extract induced epithelial-mesenchymal transition of rat alveolar type II cells]. AB - OBJECTIVE: To investigate the effect of phospholipid transfer protein(PLTP) on cigarette smoke extract(CSE) induced epithelial-mesenchymal transition(EMT) in rat alveolar Type II cells (RLE-6TN). METHODS: CSE of different concentrations (0%, 0.25%, 0.5% and 1%) was co-cultured for 2 or 3 days with RLE-6TN, either pre treated or not pre-treated with siRNA-PLTP for 6 h. Expression levels of E cadherin mRNA and Vimentin mRNA were examined by RT-PCR, while expression levels of PLTP, E-cadherin, N-cadherin and Vimentin were examined by Western blot. RESULTS: Our results showed that the expression of E-cadherin mRNA decreased in CSE-treated groups: 1.01+/-0.05, 0.74+/-0.05, 0.65+/-0.03, 0.30+/-0.08 respectively at different concentrations of CSE (0 %, 0.25%, 0.5 %, and 1.0%); while the level of Vimentin mRNA increased significantly in 1% CSE treated cells(1.88+/-0.49), compared with control cells (1.01+/-0.20). Treatment with CSE at different concentrations (0%, 0.25%, 0.5% and 1%) showed that the protein levels of PLTP were 0.42+/-0.02, 0.89+/-0.25, 1.08+/-0.18, 1.61+/-0.06 respectively; those of E-cadherin were 1.61+/-0.04, 1.08+/-0.10, 0.62+/-0.08, 0.68+/-0.17, respectively; those of N-cadherin were 0.60+/-0.14, 0.57+/-0.26, 0.88+/-0.30, 1.94+/-0.54, respectively; and those of Vimentin were 0.61+/-0.05, 0.98+/-0.16, 1.07+/-0.14, 1.34+/-0.19, respectively; all P<0.05 when the 1% CSE group was compared with the control group. EMT induced by CSE was significantly inhibited by siRNA-PLTP. CONCLUSION: PLTP may be involved in CSE induced EMT of rat alveolar cells. PMID- 27180594 TI - [Management of refractory couth]. PMID- 27180595 TI - [Research progress of relationships between tissue factor and pulmonary thrombeomblism]. PMID- 27180596 TI - [2015 annual review of interventional pulmonology]. PMID- 27180597 TI - [Application research and progress of the nanotechnology on tuberculosis]. PMID- 27180598 TI - [Clofazimine in treatment of multi-drug resistant tuberculosis]. PMID- 27180599 TI - The effects of home blood pressure monitoring on blood pressure control and treatment planning. AB - OBJECTIVES: Blood pressure monitoring is essential in hypertension, which is an important public health issue. Our objective was to compare the rates of blood pressure control and to investigate factors that affect blood pressure control in patients with hypertension. METHODS: The records of 1006 patients with hypertension were examined retrospectively. The blood pressure control rates of the 394 patients who measured their blood pressure at home (group 1) and those who did not (group 2) were compared. RESULTS: In group 1, the mean systolic and diastolic blood pressure was 123.91+/-12.63/78.64+/-8.92 mmHg measured at home, whereas it was 140.31+/-20.56/85.76+/-11.55 mmHg in the office setting (p<0.0001). In the total group (N=1006), the blood pressure control achievement rate was 56.1%. The number of cardiovascular events, hypertension duration, and the rate of being employed was higher in group 1 (p<0.0001, p<0.0001 and p=0.0001, respectively), while heart rate and grade 3-4 retinopathy was lower in group 1 (p<0.0001 for both) . Occupational status, geographical origin, BMI and the use of angiotensin converting enzyme (ACE) inhibitors were found to be the determinants of office BP control (p<0.05, p<0.05, p=0.001 and p<0.05, respectively), and BMI and grade 3-4 retinopathy findings were found to be the determinants of home BP control (p <0.05 for both). CONCLUSION: Home blood pressure monitoring is useful in preventing complications and achieving therapy compliance and is essential in diagnosis and treatment planning of hypertension. PMID- 27180601 TI - Self-inflicted burns: Are they preventable injuries? PMID- 27180602 TI - A single-center, six-year evaluation of the role of pulsed-field gel electrophoresis in suspected burn center outbreaks. AB - INTRODUCTION: Pulsed-field gel electrophoresis (PFGE) has been used as an adjunct to traditional hospital epidemiology in numerous outbreak investigations, including in burn centers. However, its most effective real-world application remains unclear, with few longitudinal descriptions of use. SETTING AND METHODS: A 425 bed military tertiary hospital with a 40 bed burn center, from July 2007 to July 2013; retrospective evaluation of hospital infection prevention records was performed and results of PFGE where used in outbreak investigation. RESULTS: Twenty-two inquiries for suspected outbreaks were performed. 418 isolates were collected from 168 subjects during this time. 325 (78%) of the isolates originated from the burn intensive care unit. 17 inquiries were for gram-negative bacteria, comprised of 5 for Acinetobacter baumannii-calcoaceticus complex, 4 Klebsiella pneumoniae, 3 Stenotrophomonas maltophilia, 2 Pseudomonas aeruginosa, and 1 of each of the following: Enterobacter cloacae, Raoultella planticola, and Aeromonas hydrophila. The other 5 inquiries were specifically for Staphylococcus aureus. The majority of investigations revealed a combination of clonal and non clonal isolates, and in no instance did PFGE contribute to targeting of interventions. CONCLUSION: PFGE contributed little to infection prevention interventions, and outbreaks resolved with increased focus on basic practices. Longitudinal studies including greater numbers of outbreaks in different settings are needed to clarify the utility of molecular typing in routine investigations. PMID- 27180603 TI - Assessment of antibodies against surface and outer membrane proteins of Anaplasma phagocytophilum in Lyme borreliosis and tick-borne encephalitis paediatric patients. AB - To examine evidence of positive antibodies against immunogenic proteins of Anaplasma phagocytophilum in patients with other tick-borne infections and to diagnose possible co-infections, 412 serum specimens were tested by immunoblotting using three specific Anaplasma antigens: surface proteins p44 and Asp62 and outer membrane protein A (OmpA). In total, 284 serum samples from children with Lyme borreliosis and 12 serum samples from children with tick-borne encephalitis were tested. Sera from patients with viral aseptic meningitis (n = 47) and from blood donors (n = 69) were used as controls. Among all serum specimens from patients with tick-borne infections submitted for this study, six samples (2.0%) showed positive IgM reactions and seven samples (2.4%) were IgG positive for A. phagocytophilum by immunoblot. Borderline reactivity was found in 30 samples (10.14%) for IgM and 36 samples (12.2%) for IgG. The difference between patients and blood donors was statistically significant for IgM (P = 0.006) and for IgG (P = 0.0007) antibodies. A statistically significant result was obtained for IgG (P = 0.02) but not for IgM between patients and children with aseptic meningitis. Immunoblot using three specific antigens provides novel information about the positivity of antibodies to A. phagocytophilum in children with other tick-borne infections. Taking into account clinical and laboratory findings of children despite antibody positivity, no case of human granulocytic anaplasmosis was demonstrated. PMID- 27180600 TI - An early granulocyte colony-stimulating factor treatment attenuates neuropathic pain through activation of mu opioid receptors on the injured nerve. AB - Several studies have shown that the mu opioid receptor (MOR) located in the peripheral nerves can be activated after nerve injury and that it attenuates peripheral nociceptive signals to the spinal dorsal horn. Various cytokines and phosphorylated-p38 (p-p38) activation in the dorsal horn also play an important role in neuropathic pain development. Granulocyte-colony stimulating factor (GCSF) is a growth factor that can stimulate granulocyte formation and has been shown to exert an analgesic effect on neuropathic pain through recruiting opioid containing leukocytes to the injured nerve. However, the underlying mechanisms are not well understood. Herein, the results of behavior tests in addition to MOR levels in the injured sciatic nerve and the levels of p-p38 and various cytokines in the spinal dorsal horn were studied in vehicle-treated or GCSF-treated chronic constriction injured (CCI) rats at different time points (i.e., 1, 3, and 7 days, respectively) after nerve injury. The results showed that a single early systemic GCSF treatment after nerve injury can up-regulate MORs in the injured nerve, which can decrease peripheral nociceptive signals. Thereafter, those changes suppress the pro-inflammatory cytokine IL-6 but enhance the anti-inflammatory cytokine IL-4, followed by decreases in p-p38 in the dorsal horn, and thus further attenuate neuropathic pain. PMID- 27180604 TI - Antiviral effect of vitamin A on norovirus infection via modulation of the gut microbiome. AB - The effect and underlying mechanism of vitamin A on norovirus infection are largely unknown. This study aimed to investigate how vitamin A administration affects the gut microbiome after norovirus infection. Here, we demonstrate that treatment with either retinol or retinoic acid (RA) inhibits murine norovirus (MNV) replication using both in vitro and in vivo models. Compositional changes in the gut microbiome associated with RA administration and/or norovirus infection were also investigated. Oral administration of RA and/or MNV significantly altered intestinal microbiome profiles. Particularly, bacterial species belonging to the Lactobacillaceae families were remarkably increased by MNV inoculation and RA administration, suggesting that the antiviral effects of RA occur via the modulation of specific microbiota. The antiviral causal effect of Lactobacillus was identified and demonstrated using in vitro models in RAW264.7 cells. The antiviral immune response to MNV was mediated by IFN-beta upregulation. This study represents the first comprehensive profiling of gut microbiota in response to RA treatment against norovirus infection. Moreover, we conclude that the abundance of Lactobacillus through gut microbiota modulation by RA is at least partially responsible for norovirus inhibition. PMID- 27180605 TI - Validated UPLC-MS/MS Methods To Quantitate Free and Conjugated Alternaria Toxins in Commercially Available Tomato Products and Fruit and Vegetable Juices in Belgium. AB - Ultraperformance liquid chromatography tandem mass spectrometry and Quick, Easy, Cheap, Effective, Rugged, and Safe based analytical methodologies to quantitate both free (alternariol (1), alternariol monomethyl ether (2), tenuazonic acid (3), tentoxin (4), altenuene (5), altertoxin-I (6)) and conjugated (sulfates and glucosides of 1 and 2) Alternaria toxins in fruit and vegetable juices and tomato products were developed and validated. Acceptable limits of quantitation (0.7-5.7 MUg/kg), repeatability (RSDr < 15.7%), reproducibility (RSDR < 17.9%), and apparent recovery (87.0-110.6%) were obtained for all analytes in all matrices investigated. 129 commercial foodstuffs were analyzed, and 3 was detected in 100% of tomato product samples (30%) and Eurotium (>20%) were predominant at 10-20 d and 30 d, respectively. The relative abundances of Rhizopus, Eurotium and Wallemia were higher than Aspergillus, because they were xerophilic and grew well on substrates with low water activity (aw). During growth, they released metabolic water, thereby favoring the growth of Aspergillus. Therefore, from 30 to 90 d, the relative abundance of Aspergillus increased while that of Rhizopus, Eurotium and Wallemia decreased. Principal Coordinate Analysis (PCoA) revealed that peanuts stored for 60-90 days and for 10-30 days clustered differently from each other. Due to low aw values (0.34-0.72) and low levels of A. flavus, nine of 51 samples were contaminated with aflatoxins. PMID- 27180616 TI - Development of a Japanese scale for assessment of paediatric normal weight. PMID- 27180615 TI - Mechanistic relationship between the vagal afferent pathway, central nervous system and peripheral organs in appetite regulation. AB - The hypothalamus is a center of food intake and energy metabolism regulation. Information signals from peripheral organs are mediated through the circulation or the vagal afferent pathway and input into the hypothalamus, where signals are integrated to determine various behaviors, such as eating. Numerous appetite regulating peptides are expressed in the central nervous system and the peripheral organs, and interact in a complex manner. Of such peptides, gut peptides are known to bind to receptors at the vagal afferent pathway terminal that extend into the mucosal layer of the digestive tract, modulate the electrical activity of the vagus nerve, and subsequently send signals to the solitary nucleus and furthermore to the hypothalamus. All peripheral peptides other than ghrelin suppress appetite, and they synergistically suppress appetite through the vagus nerve. In contrast, the appetite-enhancing peptide, ghrelin, antagonizes the actions of appetite-suppressing peptides through the vagus nerve, and appetite-suppressing peptides have attenuated effects in obesity as a result of inflammation in the vagus nerve. With greater understanding of the mechanism for food intake and energy metabolism regulation, medications that apply the effects of appetite-regulating peptides or implantable devices that electrically stimulate the vagus nerve are being investigated as novel treatments for obesity in basic and clinical studies. PMID- 27180617 TI - Facile Synthesis of N-Doped Carbon Dots as a New Matrix for Detection of Hydroxy Polycyclic Aromatic Hydrocarbons by Negative-Ion Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry. AB - N-doping carbon dots (N-CDs) were prepared by microwave-assisted pyrolysis of dl malic acid and ethanolamine as precursors. The material served as an excellent matrix for the detection of the environmental pollutants hydroxy-polycyclic aromatic hydrocarbons (OH-PAHs) by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) in negative ion mode. The obtained N-CDs exhibited good UV absorption capacity and favorable solubility. The use of the N-CDs matrix exhibited low matrix background interference and was beneficial to improve the signal response due to the specific pi-conjugated polyaromatic structure and the doping of nitrogen atoms. The developed method was found to have good reproducibility and sensitivity. The N-CDs as a new matrix also were employed for the detection of OH-PAHs in real PM2.5 samples. The mass concentrations of Sigma-hydroxy-pyrene, Sigma-dihydroxy-anthraquinone, and Sigma dihydroxy-benzo(a)pyrene on the collected PM2.5 samples ranged from 0.125 to 0.136 ng/m(3), 0.039 to 0.052 ng/m(3), and 0.053 to 0.072 ng/m(3), respectively. This work extends the application field of N-CDs and provides a good candidate of matrix for MALDI-TOF MS detection of environmental pollutants. PMID- 27180618 TI - Improving the understanding of schistosomiasis among adolescents in endemic areas in Brazil: A comparison of educational methods. AB - OBJECTIVE: To evaluate the effectiveness of two teaching strategies, both guided by the concept of dialogicity, on adolescents' knowledge about schistosomiasis and adherence to diagnostic fecal testing. METHODS: Two teaching strategies related to schistosomiasis were developed, an educational video and group conversation, which were tested in two groups of students aged 10-15 years old. Before and after the intervention, a questionnaire was applied to assess participants' knowledge about schistosomiasis and, after the intervention, two fecal samples were requested from each participant. Comparisons were performed by paired t- and McNemar tests. RESULTS: Both strategies resulted in statistically significant improvements in knowledge between the pre- and post-tests. Students who watched the video had a higher return rate of fecal samples and percentage of correct questionnaire answers, mainly on questions about schistosomiasis infection. CONCLUSION: Teaching strategies based on dialogue favored the construction of concepts about schistosomiasis that can influence the adoption of positives attitudes related to health. PRACTICAL IMPLICATIONS: Using teaching strategies based on the concept of dialogicity can favor the increase of knowledge of school age children about schistosomiasis and can influence behavioral change related to health. PMID- 27180619 TI - Spectral Camera based on Ghost Imaging via Sparsity Constraints. AB - The image information acquisition ability of a conventional camera is usually much lower than the Shannon Limit since it does not make use of the correlation between pixels of image data. Applying a random phase modulator to code the spectral images and combining with compressive sensing (CS) theory, a spectral camera based on true thermal light ghost imaging via sparsity constraints (GISC spectral camera) is proposed and demonstrated experimentally. GISC spectral camera can acquire the information at a rate significantly below the Nyquist rate, and the resolution of the cells in the three-dimensional (3D) spectral images data-cube can be achieved with a two-dimensional (2D) detector in a single exposure. For the first time, GISC spectral camera opens the way of approaching the Shannon Limit determined by Information Theory in optical imaging instruments. PMID- 27180620 TI - Effect of left atrial appendage excision on procedure outcome in patients with persistent atrial fibrillation undergoing surgical ablation. AB - BACKGROUND: Catheter ablation is less successful for treatment of persistent atrial fibrillation (PersAF) than for paroxysmal atrial fibrillation. Some studies suggest that left atrial appendage (LAA) isolation in addition to pulmonary vein isolation (PVI) is required to maximize the benefits for PersAF after ablation. OBJECTIVE: The purpose of this study was to compare the efficacy and safety of 2 surgical ablation approaches for PersAF via video-assisted thoracoscopy: PVI + box lesion and PVI + box lesion + LAA excision. METHODS: We randomly assigned 176 patients with PersAF to video-assisted thoracoscopic surgical ablation with PVI + box lesion (88 patients) or PVI + box lesion + LAA excision (88 patients). The primary endpoint was freedom from any documented atrial arrhythmia lasting >30 seconds after a single ablation procedure without antiarrhythmic drug (AAD). RESULTS: After 18 months of follow-up, 61 of 86 patients (70.9%) assigned to PVI + box lesion were free from recurrent atrial fibrillation compared to 64 of 87 patients (73.6%) assigned to PVI + box lesion + LAA excision after a single ablation procedure without AAD (P = .73). Freedom from any atrial arrhythmia after a single procedure with or without AAD was also nonsignificant (70.9% vs 74.7%, respectively). There were no significant differences between groups with regard to adverse events, including death, transient ischemic attack, stroke, pneumothorax, and hydrothorax. CONCLUSION: Among patients with PersAF, no reduction in the rate of recurrent atrial fibrillation was found when LAA excision was performed in addition to PVI and box lesion during surgical ablation. PMID- 27180621 TI - Substrate modification or ventricular tachycardia induction, mapping, and ablation as the first step? A randomized study. AB - BACKGROUND: The role and optimal sequence of ventricular tachycardia (VT) induction, mapping, and ablation when combined with substrate modification is unclear. OBJECTIVE: The purpose of this study was to test the benefits of starting the scar-related VT ablation procedure with substrate modification vs the standard protocol of VT induction, mapping, and ablation as the first step. METHODS: Forty-eight consecutive patients with structural heart disease and clinical VTs were randomized to simplified substrate ablation procedure with scar dechanneling as the first step (group 1, n = 24) or standard procedure with VT induction, mapping, and ablation followed by scar dechanneling (group 2, n = 24). Procedure and fluoroscopy times, the need for external cardioversion, acute results, and VT recurrence during follow-up were compared between groups. RESULTS: Thirty-seven patients had ischemic cardiomyopathy, 10 nonischemic cardiomyopathy, and 1 arrhythmogenic cardiomyopathy. Before substrate ablation, 32 VTs were induced and targeted for ablation in 23 patients of group 2. Procedure time (209 +/- 70 minutes vs 262 +/- 63 minutes; P = .009), fluoroscopy time (14 +/- 6 minutes vs 21+/- 9 minutes; P = .005), and electrical cardioversion (25% vs 54%; P = .039) were lower in group 1. After substrate ablation, 16 patients (66%) of group 1 and 12 patients (50%) of group 2 were noninducible (P = .242). End-procedure success (after residual inducible VT ablation) was achieved in 87.5% and 70.8% of patients, respectively (P = .155). There were no differences in VT recurrence rate between groups during a mean follow-up of 22 +/- 14 months (log rank, P = .557). CONCLUSION: VT induction and mapping before substrate ablation prolongs the procedure, radiation exposure, and the need for electrical cardioversion without improving acute results and long term ablation outcomes. PMID- 27180623 TI - Recent advances in pharmacological treatments of hyperkalemia: focus on patiromer. AB - INTRODUCTION: Hyperkalemia is a common electrolyte disorder, especially among patients with chronic kidney disease (CKD), diabetes mellitus, or heart failure, and is associated with a significantly increased risk for all-cause mortality. Hyperkalemia remains a vexing and challenging problem for clinicians, particularly in the management of patients with chronic kidney disease and congestive heart failure. Several observational and retrospective studies have reported a large gap between recommendations in guidelines and real-world practice in the implementation of RAASi therapies. RAASi treatment regimens are frequently down-titrated or discontinued following hyperkalemia events, with consequent worse outcomes than patients who remain on maximum doses. AREAS COVERED: This review covers the preclinical and clinical studies that led to the approval of patiromer for the treatment of hyperkalemia. A literature search on patiromer was carried out using the PubMed database up to December 2015. EXPERT OPINION: Recently, patiromer was approved by the FDA as the first new potassium binder for the treatment of hyperkalemia in over 50 years. Based on the results of phase II and phase III studies, we conclude that patiromer is a well-tolerated and predictable medication to consistently and safely reduce serum potassium levels and to sustain normokalemia for periods up to 52 weeks in patients with diverse underlying diseases including congestive heart failure, and chronic kidney disease. Future research questions that should be evaluated are: the role of patiromer in treating hyperkalemia and the potential to thereby allow the optimal management of resistant hypertension and the use of high dose MRAs in patients with acute decompensated heart failure. Additional research is also warranted in the potential safety benefits of reducing potassium fluctuations in patients on hemodialysis as a result of treatment of hyperkalemia with patiromer. PMID- 27180622 TI - Potentiation of Glucose-stimulated Insulin Secretion by the GPR40-PLC-TRPC Pathway in Pancreatic beta-Cells. AB - G protein-coupled receptors (GPCRs) are expressed in pancreatic beta-cells. G protein-coupled receptor 40 (GPR40) contributes to medium- or long-chain fatty acid-induced amplification of glucose-stimulated insulin secretion (GSIS), and GPR40 agonists are promising therapeutic targets in type 2 diabetes. Recently, we demonstrated that glucagon-like peptide 1, a ligand of pancreatic GPCR, activates a class of nonselective cation channels (NSCCs) and enhances GSIS. The aim of the current study was to determine whether the GPR40 signal interacts with NSCCs. A GPR40 agonist (fasiglifam) potentiated GSIS at 8.3 and 16.7 mM glucose but not 2.8 mM glucose. The NSCC current was activated by fasiglifam at 5.6 mM glucose with 100 MUM tolbutamide (-70 mV), and this activation was prevented by the presence of pyrazole-3 (transient receptor potential canonical; a TRPC3 channel blocker). Inhibitors of phospholipase C or protein kinase C (PKC) inhibited the increases in GSIS and the NSCC current induced by GPR40 stimulation. The present study demonstrates a novel mechanism for the regulation of insulin secretion by GPR40 agonist in pancreatic beta-cells. The stimulation of the GPR40-PLC/PKC TRPC3 channel pathway potentiates GSIS by the depolarization of the plasma membrane in pancreatic beta-cell. PMID- 27180626 TI - Recognition-mediated cucurbit[7]uril-heptamolybdate hybrid material: a facile supramolecular strategy for (99m)Tc separation. AB - We report the construction of a novel non-covalently held cucurbit[7]uril heptamolybdate hybrid material for the first time, and demonstrate its application as a generator bed for the facile and efficient separation of the (99m)Tc radiotracer, which is in demand for several theranostic applications. PMID- 27180624 TI - A novel podocyte gene, semaphorin 3G, protects glomerular podocyte from lipopolysaccharide-induced inflammation. AB - Kidney diseases including diabetic nephropathy have become huge medical problems, although its precise mechanisms are still far from understood. In order to increase our knowledge about the patho-physiology of kidney, we have previously identified >300 kidney glomerulus-enriched transcripts through large-scale sequencing and microarray profiling of the mouse glomerular transcriptome. One of the glomerulus-specific transcripts identified was semaphorin 3G (Sema3G) which belongs to the semaphorin family. The aim of this study was to analyze both the in vivo and in vitro functions of Sema3G in the kidney. Sema3G was expressed in glomerular podocytes. Although Sema3G knockout mice did not show obvious glomerular defects, ultrastructural analyses revealed partially aberrant podocyte foot processes structures. When these mice were injected with lipopolysaccharide to induce acute inflammation or streptozotocin to induce diabetes, the lack of Sema3G resulted in increased albuminuria. The lack of Sema3G in podocytes also enhanced the expression of inflammatory cytokines including chemokine ligand 2 and interleukin 6. On the other hand, the presence of Sema3G attenuated their expression through the inhibition of lipopolysaccharide-induced Toll like receptor 4 signaling. Taken together, our results surmise that the Sema3G protein is secreted by podocytes and protects podocytes from inflammatory kidney diseases and diabetic nephropathy. PMID- 27180625 TI - Dietary and physical activity of adult patients with type 2 diabetes in Zhejiang province of eastern China: Data from a cross-sectional study. AB - AIMS/INTRODUCTION: Lifestyle management helps improve the clinical outcome of patients with type 2 diabetes. The present study aimed to obtain lifestyle data on the dietary and physical activity of adult type 2 diabetes patients in Zhejiang province of eastern China for better patient education and improvement of clinical management. MATERIALS AND METHODS: A cross-sectional survey of 607 adult type 2 diabetes patients was carried out in 12 hospitals within eight cities of Zhejiang province. Data were collected for sex, age, basic physical measurement (blood pressure, height, weight, waist circumference and hip circumference), dietary favor and habit (vegetarian diets vs meat diets, preference of salty or light flavors), detailed dietary intake (24-h recall method), as well as the weekly physical activity. RESULTS: The mean age of the patients in the analysis was 56.39 +/- 12.29 years, and 38.71% of the patients had higher levels of body mass index than recommended. The average daily total energy intake was 1887.71 +/- 575.10 kcal. The percentage of calories from carbohydrate, protein and fat were 61.36 +/- 11.59%, 13.29 +/- 3.37% and 25.35 +/ 11.16%, respectively. For physical activity, the patients generally spent most of their daily time sitting and sleeping, and the time for moderate vigorous activity was limited. CONCLUSIONS: Adult patients with type 2 diabetes in Zhejiang province have a relatively high carbohydrate and low protein diet, with very limited physical activity. Patient education to achieve a better lifestyle intervention needs to improve in this region. PMID- 27180627 TI - Planned vaginal delivery versus planned cesarean delivery in cases of low-lying placenta. AB - OBJECTIVE: To assess the applicability of trial of labor in cases of low-lying placenta. METHODS: In this observational cohort study, we collected data from the women with low-lying placenta delivered at our hospital between April 2012 and December 2015. Low-lying placenta was diagnosed when the length from the placental lowest edge to the internal cervical os (placenta-os distance) was 0-20 mm at 36 gestational weeks. Planned mode of delivery for each case was determined by patient's preference. Maternal and neonatal outcomes were compared between the planned vaginal delivery group (N = 11) and the planned cesarean delivery group (N = 7). RESULTS: All the women in the planned cesarean delivery group underwent scheduled cesarean section at 37-38 gestational weeks. Three cases in the planned vaginal delivery group required emergency cesarean section for uncontrollable antepartum bleeding. The intrapartum blood loss was significantly smaller in the planned vaginal delivery group than in the planned cesarean delivery group (946 +/- 204 g vs. 1649 +/- 256 g, p = 0.047). Umbilical arterial blood pH was similar between the two groups. All the women requiring emergency cesarean section were accompanied by marginal sinus. CONCLUSIONS: Trial of labor can be offered to all the women with low-lying placenta except for those accompanied by marginal sinus. PMID- 27180630 TI - Diagnosis of Intracranial Artery Dissection. AB - Cerebral arterial dissection is defined as a hematoma in the wall of a cervical or an intracranial artery. Cerebral arterial dissection causes arterial stenosis, occlusion, and aneurysm, resulting in acute infarction and hemorrhage. Image analysis by such methods as conventional angiography, computed tomography, magnetic resonance imaging, and so on plays an important role in diagnosing cerebral arterial dissection. In this study, we explore the methods and findings involved in the diagnosis of cerebral arterial dissection. PMID- 27180631 TI - Approach to the Treatment of Methanol Intoxication. AB - Methanol intoxication is an uncommon but serious poisoning. Its adverse effects are due primarily to the impact of its major metabolite formic acid and lactic acid resulting from cellular hypoxia. Symptoms including abdominal pain and loss of vision can appear a few hours to a few days after exposure, reflecting the time necessary for accumulation of the toxic byproducts. In addition to a history of exposure, increases in serum osmolal and anion gaps can be clues to its presence. However, increments in both parameters can be absent depending on the nature of the toxic alcohol, time of exposure, and coingestion of ethanol. Definitive diagnosis requires measurement with gas or liquid chromatography, which are laborious and expensive procedures. Tests under study to detect methanol or its metabolite formate might facilitate the diagnosis of this poisoning. Treatment can include administration of ethanol or fomepizole, both inhibitors of the enzyme alcohol dehydrogenase to prevent formation of its metabolites, and hemodialysis to remove methanol and formate. In this Acid-Base and Electrolyte Teaching Case, a patient with methanol intoxication due to ingestion of model airplane fuel is described, and the value and limitations of current and new diagnostic and treatment measures are discussed. PMID- 27180633 TI - Spectral watermarking in femtosecond stimulated Raman spectroscopy: resolving the nature of the carotenoid S* state. AB - A new method for recording femtosecond stimulated Raman spectra was developed that dramatically improves and automatizes baseline problems. Instead of using a narrowband Raman source, the experiment is performed using shaping of a broadband source. This allows locking the signal into carefully crafted watermarks that can be recovered from measured data with high fidelity. The approach uses unique properties of Raman scattering, thus allowing a direct recording of stimulated Raman signals with robust rejection of baselines and fixed-pattern-noise. Low cost technology for generating required pulse-shapes was developed and demonstrated. The methodology is applicable to any Raman experiment but primarily targets Femtosecond Stimulated Raman spectroscopy (FSRS) where a lack of robust methods for parasitic signal rejection has been a major obstacle in the practical development of the field in the last decade. The delivered improvement in FSRS experiments was demonstrated by recording evidence that the so-called S* state of carotenoids in solution corresponds to the optically forbidden S1 state of a sparsely populated carotenoid conformation. PMID- 27180632 TI - Deleterious effects of incense smoke exposure on kidney function and architecture in male albino rats. AB - CONTEXT: Previous studies, including ours, have shown adverse effects of incense smoke on human health. However, the effect of incense smoke on kidney function and structure remains unknown. OBJECTIVE: To evaluate possible adverse effects of incense smoke on kidney function and architecture in albino rats after chronic exposure to Arabian incense. MATERIALS AND METHODS: Emission characteristics including particle size distribution, volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs) were determined by gravimetric and GCMS analyses. Kidney functional markers, oxidative stress and inflammatory markers were measured by standard or ELISA based procedures. Ultrastructural changes in kidney were examined by transmission electron microscope (TEM) and the gene expression of xenobiotic metabolizing enzymes including cytochrome P-450-1A1 (CYP1A1) and CYP1A2 were studied by real time PCR. RESULTS: Rats exposed to incense smoke demonstrated a significant increase in serum creatinine, uric acid, blood urea nitrogen (BUN), tissue malondialdehyde (MDA), tumor necrosis factor alpha (TNF-alpha) and interleukin-4 (IL-4) levels and a significant decline in tissue reduced glutathione (GSH) and catalase activity. Incense smoke exposed rats also displayed marked ultrastructural changes in kidney tissue. Further, a significant increase in tissue gene expression of both CYP1A1 and CYP1A2 was noted in exposed rats. DISCUSSION: Changes to kidney functional markers and architecture appear to be mediated through augmented oxidative stress and inflammation. CONCLUSION: Long-term exposure to incense smoke may have deleterious effects on kidney function and architecture. Though, inhalation is the rout of exposure, findings of this study underscore that incense smoke may also have an effect on non-pulmonary tissues. PMID- 27180634 TI - Estimating the probability of bacterial infection using a novel biomarker among pediatric patients in the emergency department. AB - CONTEXT: IL-27 is a novel biomarker to identify bacterial infection in children. OBJECTIVE: IL-27 was evaluated among pediatric emergency department (ED) patients and compared with procalcitonin (PCT). METHODS AND RESULTS: Children undergoing blood, urine, or cerebrospinal fluid cultures had IL-27 and PCT assays performed. Bacterial infection was defined as a positive culture or a clinical diagnosis based on chart review. IL-27 and PCT were increased among patients with bacterial infection and demonstrated comparable AUC's (0.62 versus 0.61). A decision tree incorporating IL-27, PCT, and white blood cell count improved the AUC (0.80). CONCLUSION: IL-27 is a viable candidate biomarker to identify bacterial infection among ED patients and is comparable with PCT. PMID- 27180635 TI - Lung inflammation does not affect the clearance kinetics of lipid nanocapsules following pulmonary administration. AB - Lipid nanocapsules (LNCs) are semi-rigid spherical capsules with a triglyceride core that present a promising formulation option for the pulmonary delivery of drugs with poor aqueous solubility. Whilst the biodistribution of LNCs of different size has been studied following intravenous administration, the fate of LNCs following pulmonary delivery has not been reported. We investigated quantitatively whether lung inflammation affects the clearance of 50nm lipid nanocapsules, or is exacerbated by their pulmonary administration. Studies were conducted in mice with lipopolysaccharide-induced lung inflammation compared to healthy controls. Particle deposition and nanocapsule clearance kinetics were measured by single photon emission computed tomography/computed tomography (SPECT/CT) imaging over 48 h. A significantly lower lung dose of (111)In-LNC50 was achieved in the lipopolysaccharide (LPS)-treated animals compared with healthy controls (p<0.001). When normalised to the delivered lung dose, the clearance kinetics of (111)In-LNC50 from the lungs fit a first order model with an elimination half-life of 10.5+/-0.9h (R(2)=0.995) and 10.6+/-0.3h (R(2)=1.000) for healthy and inflamed lungs respectively (n=3). In contrast, (111)In diethylene triamine pentaacetic acid (DTPA), a small hydrophilic molecule, was cleared rapidly from the lungs with the majority of the dose absorbed within 20min of administration. Biodistribution to lungs, stomach-intestine, liver, trachea-throat and blood at the end of the imaging period was unaltered by lung inflammation. This study demonstrated that lung clearance and whole body distribution of lipid nanocapsules were unaffected by the presence of acute lung inflammation. PMID- 27180636 TI - Inhibition of fibrous dysplasia via blocking Gsalpha with suramin sodium loaded with an alendronate-conjugated polymeric drug delivery system. AB - Suramin sodium (SS), which can directly inhibit the committed step of Gsalpha activation, seems to be a promising drug for treating fibrous dysplasia (FD). Therefore, how to efficiently deliver SS to the lesion site becomes an urgent problem to be solved. Here a bone-targeted and pH-sensitive drug delivery system was constructed to deliver SS for treating FD with high efficiency. The novel type of bone-targeted cationic hyperbranched poly(amine-ester) (HBPAE) was synthesized by the proton-transfer polymerization of triethanolamine and glycidyl methacrylate, followed by surface carboxyl-modification and then conjugation of an alendronate (ALE) bone-targeting moiety. The resultant Suc-HBPAE-ALE formed nanoparticles in aqueous solution, and SS could be encapsulated into the Suc HBPAE-ALE nanoparticles via electrostatic attraction. The dynamic light scattering (DLS) and transmission electron microscopy (TEM) assays showed that the SS-loaded nanoparticles had a spherical morphology with a mean diameter of 65 nm. The strong affinity of Suc-HBPAE-ALE nanoparticles to bone was verified by the hydroxyapatite (HA) adsorbing experiment. The therapeutic potential of the SS loaded Suc-HBPAE-ALE nanoparticles was evaluated via the methylthiazoletetrazolium (MTT) assay and flow cytometry (FCM) analysis against FD cells. The experimental results indicated that the SS-loaded Suc-HBPAE-ALE nanoparticles were a highly promising drug delivery system with high efficiency for inhibiting the proliferation of diseased FD cells. PMID- 27180637 TI - Two field-induced slow magnetic relaxation processes in a mononuclear Co(ii) complex with a distorted octahedral geometry. AB - A distorted octahedral Co(II) complex is reported with homoscorpionate ligands. This complex comprised a field-induced single-molecule magnet, showing two slow relaxation processes under a low dc field (<800 Oe) and only one process under a high dc field (>=800 Oe), which was an unusually discovery for 3d metal ions. On the basis of the ac magnetic data, we show for the first time that one of the slow relaxation processes in the low dc field originates from intermolecular dipolar interactions. Interestingly, the Raman process is predominant in the spin reversal relaxation process. The origin of the behaviours of the complex was elucidated by ab initio calculations. PMID- 27180638 TI - Nanobubbles at Hydrophilic Particle-Water Interfaces. AB - The puzzling persistence of nanobubbles breaks Laplace's law for bubbles, which is of great interest for promising applications in surface processing, H2 and CO2 storage, water treatment, and drug delivery. So far, nanobubbles have mostly been reported on hydrophobic planar substrates with atomic flatness. It remains a challenge to quantify nanobubbles on rough and irregular surfaces because of the lack of a characterization technique that can detect both the nanobubble morphology and chemical composition inside individual nanobubble-like objects. Here, by using synchrotron-based scanning transmission soft X-ray microscopy (STXM) with nanometer resolution, we discern nanoscopic gas bubbles of >25 nm with direct in situ proof of O2 inside the nanobubbles at a hydrophilic particle water interface under ambient conditions. We find a stable cloud of O2 nanobubbles at the diatomite particle-water interface hours after oxygen aeration and temperature variation. The in situ technique may be useful for many surface nanobubble-related studies such as material preparation and property manipulation, phase equilibrium, nucleation kinetics, and relationships with chemical composition within the confined nanoscale space. The oxygen nanobubble clouds may be important in modifying particle-water interfaces and offering breakthrough technologies for oxygen delivery in sediment and/or deep water environments. PMID- 27180639 TI - Bronchopulmonary C-fibers' IL1RI contributes to the prolonged apneic response to intra-atrial injection of capsaicin by prenatal nicotinic exposure in rat pups. AB - Prenatal nicotinic exposure (PNE) as a SIDS model reportedly sensitizes bronchopulmonary C-fibers (PCFs), contributing to the prolonged PCF-mediated apnea in rat pups, but the relevant mechanisms are not fully understood. Pulmonary IL-1beta upregulated by cigarette smoke is known to stimulate or sensitize PCFs acting via IL-1 type I receptor (IL1RI) and inhibit inspiration frequency. Because of its upregulation observed in SIDS victims, we hypothesized that PNE increased pulmonary IL-1beta release and IL1RI expression in pulmonary C neurons via action on alpha7 nicotinic acetylcholine receptors (alpha7nAChR) to induce the prolonged PCF-mediated apnea. IL-1beta in BALF and IL1RI in the nodose/jugular (N/J) ganglion and vagal pulmonary C-neurons retrogradely-traced were compared between Ctrl (saline) and PNE pups and among the vehicle-treated Ctrl and PNE and methyllycaconitine (a selective alpha7nAChR antagonist)-treated PNE pups. The effect of IL-1RI blockade (IL-1Ra) on the PCF-mediated apnea was also compared between Ctrl and PNE pups. PNE significantly elevated IL-1beta in BALF and upregulated IL1RI gene and protein expression in N/J ganglia and gene in vagal pulmonary C-neurons. All of these responses were eliminated by pretreatment with blockade of alpha7nAChR. In addition, the prolonged PCF-mediated apnea in PNE pups was significantly shortened by right atrial bolus injection of IL-1Ra. We conclude that PNE enhances pulmonary IL-1beta release and PCF IL1RI expression acting via alpha7nAChR in contributing to sensitization of PCFs and prolongation of the PCF-mediated apneic response. PMID- 27180641 TI - Mg(2+)-Dependent Control of the Spatial Arrangement of Rhodococcus erythropolis PR4 Cells in Aqueous-Alkane Two Phase Culture Containing n-Dodecane. AB - We recently reported that a close relationship exists between alkane carbon-chain length, cell growth, and translocation frequency in Rhodococcus. In the present study, we examined the regulation of the spatial arrangement of cells in aqueous alkane two phase cultures. An analysis of the effects of minerals on cell localization revealed that changes in the concentration of MgSO4 in two phase cultures containing n-dodecane (C12) altered cell localization from translocation to adhesion and vice versa. Our results indicate that the spatial arrangement of cells in two phase culture systems is controlled through the regulation of MgSO4 concentrations. PMID- 27180642 TI - Multidimensional targeting for tailoring: a comment on Ogden (2016). PMID- 27180640 TI - Diversity, Community Composition and Abundance of Anammox Bacteria in Sediments of the North Marginal Seas of China. AB - Over the past few decades, anammox bacteria have been recognized as key players that contribute significantly to the release of large amounts of nitrogen in the global marine nitrogen cycle. In the present study, the diversity, community composition, and abundance of anammox bacteria from the sediments of four diverse regions in the north marginal seas in China were determined via clone library construction and a quantitative PCR analysis. The clone libraries retrieved by the 16S rRNA gene and Hzo gene markers indicated that "Candidatus Scalindua" was the predominant group throughout the sites examined. The 16S rRNA gene clone libraries revealed exceptional diversity by identifying two potential novel anammox clades, as evidenced by the high sequence similarities between these two clades and known anammox genera, and their unique phylogenetic positions with high bootstrap values. However, their potential roles in the anammox reaction need to be validated. Six novel members of Planctomycetes, divergent from the known genera of anammox bacteria, were also detected. A phylogenetic analysis by Hzo protein sequences revealed the existence of two known genera, i.e., "Candidatus Jettenia" and "Candidatus Anammoxoglobus", which are rarely captured from marine sediments. Among all ecological parameters investigated, the distribution patterns and composition of anammox bacteria were found to be influenced by salinity, total organic matter, and temperature. The abundance of the anammox bacterial 16S rRNA gene from the sites examined ranged between 3.95*10(5) and 9.21*10(5) copies g(-1) wet sediment and positively correlated with the median size of the sediment sample. PMID- 27180643 TI - Corrigendum to "APOA5 variants predispose hyperlipidemic patients to atherogenic dyslipidemia and subclinical atherosclerosis" [Atherosclerosis 240/1 (2015) 98 104]. PMID- 27180644 TI - Coronary artery calcium density for the prediction of mortality in CKD patients: One size does not fit all. PMID- 27180645 TI - Corrigendum to "Molecular diagnosis of hypobetalipoproteinemia: An ENID review" [Atherosclerosis 195 (2) (2007) 19-27]. PMID- 27180647 TI - Isolation of atomically precise mixed ligand shell PdAu24 clusters. AB - Exposure of PdAu24(2-PET)18 (2-PET: 2-phenylethylthiolate) to BINAS (1,1 binaphthyl-2,2-dithiol) leads to species of composition PdAu24(2-PET)18 2x(BINAS)x due to ligand exchange reactions. The BINAS adsorbs in a specific mode that bridges the apex and one core site of two adjacent S(R)-Au-S(R)-Au-S(R) units. Species with different compositions of the ligand shell can be separated by HPLC. Furthermore, site isomers can be separated. For the cluster with exactly one BINAS in its ligand shell only one isomer is expected due to the symmetry of the cluster, which is confirmed by High-Performance Liquid Chromatography (HPLC). Addition of a second BINAS to the ligand shell leads to several isomers. In total six distinguishable isomers are possible for PdAu24(2-PET)14(BINAS)2 including two pairs of enantiomers concerning the adsorption pattern. At least four distinctive isomers are separated by HPLC. Calculations indicate that one of the six possibilities is energetically disfavoured. Interestingly, diastereomers, which have an enantiomeric relationship concerning the adsorption pattern of chiral BINAS, have significantly different stabilities. The relative intensity of the observed peaks in the HPLC does not reflect the statistical weight of the different isomers. This shows, as supported by the calculations, that the first adsorbed BINAS molecule influences the adsorption of the second incoming BINAS ligand. In addition, experiments with the corresponding Pt doped gold cluster reveal qualitatively the same behaviour, however with slightly different relative abundances of the corresponding isomers. This finding points towards the influence of electronic effects on the isomer distribution. Even for clusters containing more than two BINAS ligands a limited number of isomers were found, which is in contrast to the corresponding situation for monothiols, where the number of possible isomers is much larger. PMID- 27180646 TI - Nocturia and prevalence of erectile dysfunction in Japanese patients with type 2 diabetes mellitus: The Dogo Study. AB - AIMS/INTRODUCTION: Several epidemiological studies have reported a positive association between nocturia and erectile dysfunction (ED). Yet only limited evidence exists regarding the association between nocturia and ED among patients with type 2 diabetes mellitus, although nocturia and ED are common among type 2 diabetes mellitus patients. MATERIAL AND METHODS: Study participants were 332 male Japanese patients with type 2 diabetes mellitus, aged 19-70 years, who had undergone blood tests at our institutions. A self-administered questionnaire was used to collect information on the variables under study. Adjustment was made for age, body mass index, hypertension, stroke, ischemic heart disease, glycated hemoglobin and diabetic neuropathy. ED, moderate to severe ED and severe ED were defined as present when a participant had a Sexual Health Inventory for Men score <22, <12 and <8, respectively. Study participants were considered to have nocturia if they answered 'once or more' to the question: 'Within 1 week, how many times do you typically wake up to urinate from sleeping at night until waking in the morning?' RESULTS: The prevalence of nocturia was 79.8%. Nocturia was independently positively associated with ED and moderate to severe ED: the adjusted odds ratios were 7.86 (95% confidence interval 2.11-33.56) and 2.17 (95% confidence interval 1.16-4.12), respectively. The positive association between nocturia and severe ED fell just short of significance. CONCLUSIONS: In Japanese men with type 2 diabetes mellitus, nocturia might be associated with ED and moderate to severe ED. PMID- 27180648 TI - [Compliance with medical treatment in primary open-angle glaucoma in Lome]. AB - OBJECTIVE: To assess the compliance rate among glaucoma patients with medical treatment, to investigate the factors influencing their attitude and survey their expectations vis-a-vis the doctor. PATIENTS AND METHODS: This is a prospective descriptive study conducted in four eye clinics in Lome from January 2013 to July 2013. It included all glaucoma patients aged 40 years and above who have been under medical treatment for at least 6 months, with no history of surgical treatment of glaucoma. The evaluation was performed on the basis of a questionnaire. Compliance was rated good, fair or poor according to the regularity of treatment, compliance with the prescribed dosage and schedule of instillations, good instillation technique and compliance with follow-up visits. Patients consented to participate in the survey. RESULTS: A total of 107 patients responded to our questionnaire. There were 43 men and 64 women with a sex ratio (M/F) of 0.67. The mean age was 52.40+/-11.03 years. In total, 7.5% of patients were illiterate. Compliance rate was estimated good in 10.3% of cases, fair in 65.4% of cases, and poor in 24.3% of cases. Only the regularity of treatment, schedule adherence and good instillation technique, as well as compliance with monitoring visits were found as significant factors (P<0.05). Concerning patients' expectations vis-a-vis the doctor, 49.5% said they expected nothing from the doctor, 12.1% were hoping for advice and moral support, and 11.2% were hoping for the prescription of effective but less expensive eye drops. CONCLUSION: A good compliance rate was very low. The improvement of this compliance rate requires better information, education and communication for behavior change, and it also requires a higher quality of care and accessibility of anti-glaucoma drugs. PMID- 27180649 TI - Photoprotection and photoreception of intraocular lenses under xenon and white LED illumination. AB - OBJECTIVE: To analyze the photoprotection and phototransmission that various intraocular lenses (IOLs) provide under the illumination of a xenon (Xe) lamp and white LEDs (light emitting diode). METHODS: The spectral transmission curves of six representative IOLs were measured using a Perkin-Elmer Lambda 35 UV/VIS spectrometer. Various filtering simulations were performed using a Xe lamp and white LEDs. The spectral emissions of these lamps were measured with an ILT-950 spectroradiometer. RESULTS: The IOLs analyzed primarily show transmission of nearly 100% in the visible spectrum. In the ultraviolet (UV) region, the filters incorporated in the various IOLs did not filter equally, and some of them let an appreciable amount of UV through. The Xe lamp presented a strong emission of ultraviolet A (UVA), and its emission under 300nm was not negligible. The white LED did not present an appreciable emission under 380nm. CONCLUSIONS: The cut-off wavelength of most filters is between 380 and 400nm (Physiol Hydriol60C((r)), IOLTECH E4T((r)), Alcon SA60AT((r)), Alcon IQ SN60WF((r))), so that their UV protection is very effective. Nonetheless, the IOL OPHTEC Oculaid((r)) contains a filter that, when a Xe lamp is used, lets through up to 20% for 350nm and up to 15% for 300nm, which at this point is ultraviolet B (UVB). The OPHTEC((r)) Artisan IOL has a transmission peak below 300nm, which must be taken into account under Xe illumination. White LEDs do not emit energy below 380nm, so no special protection is required in the UV region. PMID- 27180650 TI - Bad News or Really Bad News? PMID- 27180654 TI - Utility of hypertriglyceridemic waist phenotype for predicting incident type 2 diabetes: The Isfahan Diabetes Prevention Study. AB - AIM/INTRODUCTION: We evaluated the association between hypertriglyceridemic waist (HTW) phenotype and the risks of type 2 diabetes in an Iranian high-risk population. MATERIALS AND METHODS: We analyzed 7-year follow-up data (n = 1,865) in non-diabetic first-degree relatives of consecutive patients with type 2 diabetes aged 30-70 years. The primary outcome was the diagnosis of type 2 diabetes based on repeated oral glucose tolerance tests. We used multiple logistic regressions to estimate the odds ratio (OR) for incident type 2 diabetes across four groups according to baseline fasting serum triglycerides (TG) level and waist circumference (WC): normal WC and normal TG, normal WC and high TG, enlarged WC and normal TG, and HTW (enlarged WC high TG). RESULTS: The HTW phenotype at baseline was associated with the incidence of type 2 diabetes. Those with HTW were 2.4-fold (OR 2.36, 95% confidence interval 1.61-3.44), those with normal WC high TG were 1.9-fold (OR 1.87, 95% confidence interval 1.29-2.70) and those with enlarged WC but normal TG were 2.8-fold (OR 2.84, 95% confidence interval 1.96-4.13) more likely to develop type 2 diabetes than those with normal WC and normal TG. CONCLUSIONS: These data provide further evidence that the HTW phenotype is a robust predictor of type 2 diabetes in high-risk individuals in Iran, and the predictive power is not higher than that of simple enlarged WC and normal TG, emphasizing the importance of enlarged WC to the development of type 2 diabetes. PMID- 27180651 TI - The elongation factor Spt5 facilitates transcription initiation for rapid induction of inflammatory-response genes. AB - A subset of inflammatory-response NF-kappaB target genes is activated immediately following pro-inflammatory signal. Here we followed the kinetics of primary transcript accumulation after NF-kappaB activation when the elongation factor Spt5 is knocked down. While elongation rate is unchanged, the transcript synthesis at the 5'-end and at the earliest time points is delayed and reduced, suggesting an unexpected role in early transcription. Investigating the underlying mechanism reveals that the induced TFIID-promoter association is practically abolished by Spt5 depletion. This effect is associated with a decrease in promoter-proximal H3K4me3 and H4K5Ac histone modifications that are differentially required for rapid transcriptional induction. In contrast, the displacement of TFIIE and Mediator, which occurs during promoter escape, is attenuated in the absence of Spt5. Our findings are consistent with a central role of Spt5 in maintenance of TFIID-promoter association and promoter escape to support rapid transcriptional induction and re-initiation of inflammatory response genes. PMID- 27180655 TI - Aquaphilus dolomiae extract counteracts the effects of cutaneous S. aureus secretome isolated from atopic children on CD4+ T cell activation. AB - CONTEXT: Skin microbiota takes part in the control of cutaneous inflammation. In skin diseases such as atopic dermatitis (AD) cutaneous dysbiosis and the emergence of Staphylococcus aureus contribute to the pathophysiology of the disease. New therapeutic approaches consist in topical application of natural products able to counteract S. aureus effects through activation of resident immune cells producing anti-inflammatory cytokines such as IL-10. OBJECTIVE: This study investigates the potential immunosuppressive properties of Aquaphilus dolomiae (Neisseriaceae), a flagellated bacterium contained in Avene Thermal Spring Water used in hydrotherapy treatments of AD patients. MATERIALS AND METHODS: An aqueous protein extract of Aquaphilus dolomiae (ADE, 60 MUg/mL) was added to human monocyte-derived dendritic cells (moDC) for 24 h. Expression of HLA-DR, CD86 and CD83 was evaluated by flow cytometry and released cytokines (IL 10, IL-12) by cytometry bead array assay. The proliferation of allogeneic CFSE labelled CD4+ T cells stimulated with ADE-conditioned moDC and S. aureus secretome was analysed by flow cytometry. RESULTS: MoDC exposed to ADE expressed lower levels of HLA-DR and CD86 than untreated cells, no CD83 and secreted barely detectable IL-12 but high amounts of IL-10 (N = 12, p < 0.0002). The proliferative effect of S. aureus secretome on CD4+ T cells was reduced (p < 0.001) in the presence of ADE-moDC. CONCLUSION: ADE counteracted the mitogenic effect of a S. aureus secretome on CD4+T cells. Owing to the role of S. aureus colonization in driving inflammation in AD the immunosuppressive property of the ADE might be useful to reduce disease severity. PMID- 27180656 TI - Size matters: Perceived depth magnitude varies with stimulus height. AB - Both the upper and lower disparity limits for stereopsis vary with the size of the targets. Recently, Tsirlin, Wilcox, and Allison (2012) suggested that perceived depth magnitude from stereopsis might also depend on the vertical extent of a stimulus. To test this hypothesis we compared apparent depth in small discs to depth in long bars with equivalent width and disparity. We used three estimation techniques: a virtual ruler, a touch-sensor (for haptic estimates) and a disparity probe. We found that depth estimates were significantly larger for the bar stimuli than for the disc stimuli for all methods of estimation and different configurations. In a second experiment, we measured perceived depth as a function of the height of the bar and the radius of the disc. Perceived depth increased with increasing bar height and disc radius suggesting that disparity is integrated along the vertical edges. We discuss size-disparity correlation and inter-neural excitatory connections as potential mechanisms that could account for these results. PMID- 27180658 TI - Fully Aromatic High Performance Thermoset via Sydnone-Alkyne Cycloaddition. AB - We have developed an efficient synthetic platform for the preparation of a new class of high performance thermosets based on the 1,3-dipolar cycloaddition of a bifunctional sydnone with a trifunctional alkyne. These processable materials possess outstanding thermal stability, with Td5% of 520 degrees C and a weight loss of <0.1% per day at 225 degrees C (both in air). Key to this performance is the stability of the starting functional groups that allows for reactive B staging via simple thermal activation to give fully aromatic and highly cross linked polypyrazole-based thermosets. PMID- 27180659 TI - Dynamics of nanocubes embedding into polymer films investigated via spatially resolved plasmon modes. AB - Integration of nanoparticles into thin films is essential for the development of functional materials, studies of fundamental interfacial processes, and exploitation of inherent properties from the particles themselves. In this work, we systematically investigate the process of incorporation of silver nanocubes into thin polystyrene films at temperatures just above the polymer glass transition. The process of nanocrystal incorporation can be precisely monitored via far-field spectroscopy to observe the response of spatially resolved hybrid plasmon modes. Each plasmon resonance has a distinct dynamic range and maximum sensitivity forming a complementary set of nanorulers that operates over a distance comparable to the edge length of the cubes. The approach explored in this work is a general robust method for the development of long-range polychromatic nanorulers. PMID- 27180657 TI - Probiotics as adjunctive therapy for preventing Clostridium difficile infection - What are we waiting for? AB - : With the end of the golden era of antibiotic discovery, the emergence of a new post-antibiotic age threatens to thrust global health and modern medicine back to the pre-antibiotic era. Antibiotic overuse has resulted in the natural evolution and selection of multi-drug resistant bacteria. One major public health threat, Clostridium difficile, is now the single leading cause of hospital-acquired bacterial infections and is by far the most deadly enteric pathogen for the U.S. POPULATION: Due to the high morbidity and mortality and increasing incidence that coincides with antibiotic use, non-traditional therapeutics are ideal alternatives to current treatment methods and also provide an avenue towards prevention. Despite the need for alternative therapies to antibiotics and the safety of most probiotics on the market, researchers are inundated with regulatory issues that hinder the translational science required to push these therapies forward. This review discusses the regulatory challenges of probiotic research, expert opinion regarding the application of probiotics to C. difficile infection and the efficacy of probiotics in preventing this disease. PMID- 27180660 TI - CPR-associated right ventricular rupture in the setting of pulmonary embolism. AB - Cardiopulmonary resuscitation (CPR) is an inherently traumatic procedure. Successful resuscitations are often complicated by iatrogenic injuries to structures of the neck, thorax, or abdomen. Rib and sternal fractures are the most frequently induced injuries. However, rare and life-threatening trauma to vital organs such as the heart may also occur during CPR. We describe a novel case of CPR-associated right ventricular rupture in a woman with acute-on-chronic pulmonary embolism and no known pre-existing cardiac disease. We propose that chest compressions in the setting of elevated right ventricular pressure resulted in cardiac rupture, in this case. PMID- 27180661 TI - Fetal exposure to parental smoking and the risk of type 2 diabetes: Are lifestyle related factors more important? AB - Current evidence suggests that although fetal exposure to smoking might increase the risk of type 2 diabetes in later life, lifestyle factors either during pregnancy or in adulthood may play a more important role. A 'family-based association study' design might be helpful to detangle the relation among intrauterine exposure, lifestyle factors, and risk of diabetes in later life. PMID- 27180662 TI - Technique: CRISP(e)R genetic mapping. PMID- 27180664 TI - [Obesity paradoxes]. AB - Obesity (esp. abdominal type) was still considered as a risk factor for cardiovascular disease. During the last decade has a new phenomenon appeared: "obesity paradox", i.e. patients with high BMI die less frequently than patients with low BMI. Obesity paradox was described first in patients with chronic renal failure, heart failure or in oncological patients, later on in patients with cardiovascular disease and now also in patients with type 2 diabetes. In comparison with population studies, BMI associated with low cardiovascular mortality in patients with Type 2 diabetes is shifted to the higher level than in subjects from general population. Mechanisms of obesity paradox is not yet clarified. PMID- 27180663 TI - Foxf2 is required for secondary palate development and Tgfbeta signaling in palatal shelf mesenchyme. AB - The secondary palate separates the oral from the nasal cavity and its closure during embryonic development is sensitive to genetic perturbations. Mice with deleted Foxf2, encoding a forkhead transcription factor, are born with cleft palate, and an abnormal tongue morphology has been proposed as the underlying cause. Here, we show that Foxf2(-/-) maxillary explants cultured in vitro, in the absence of tongue and mandible, failed to close the secondary palate. Proliferation and collagen content were decreased in Foxf2(-/-) palatal shelf mesenchyme. Phosphorylation of Smad2/3 was reduced in mutant palatal shelf, diagnostic of attenuated canonical Tgfbeta signaling, whereas phosphorylation of p38 was increased. The amount of Tgfbeta2 protein was diminished, whereas the Tgfb2 mRNA level was unaltered. Expression of several genes encoding extracellular proteins important for Tgfbeta signaling were reduced in Foxf2( )(/)(-) palatal shelves: a fibronectin splice-isoform essential for formation of extracellular Tgfbeta latency complexes; Tgfbr3 - or betaglycan - which acts as a co-receptor and an extracellular reservoir of Tgfbeta; and integrins alphaV and beta1, which are both Tgfbeta targets and required for activation of latent Tgfbeta. Decreased proliferation and reduced extracellular matrix content are consistent with diminished Tgfbeta signaling. We therefore propose that gene expression changes in palatal shelf mesenchyme that lead to reduced Tgfbeta signaling contribute to cleft palate in Foxf2(-)(/)(-) mice. PMID- 27180665 TI - [Clinical aspects of pharmacological treatment of diabetic neuropathy - cooperation with neurologists and diabetologists]. AB - The development and progression of symptomatic diabetic neuropathy (SDN) is linked to hyperglycemia. The effort to improve compensation of diabetes mellitus during therapy is therefore very important. This is where the cooperation between the diabetologist and neurologist within therapy plays an important role. The pharmaco-logical therapy of symptomatic sensitive peripheral diabetic neuropathy is difficult and with a less than satisfactory effect. A variety of active substances is used in symptomatic therapy, primarily designed for intervention in other pathological conditions. The recommended guidelines include antidepressants, anticonvulsants, opiates and their derivatives. However this therapy brings with it a relatively high incidence of adverse effects which detract from patients adherence to treatment. Very good results are reached by the therapy with thioctacid. PMID- 27180666 TI - [Pharmacogenetics of oral antidiabetic treatment]. AB - Pharmacogenetics is the study of how genes (individual genotypes) affect a persons response to drugs. At present, recommendations made about the treatment of some monogenic forms of diabetes are based on genetic diagnostics. The first studies in the field of pharmacogenetics of oral antidiabetics have now been published which have identified associations of individual genetic variants with response to treatment. The response to sulfonylurea derivatives was significantly associated with the variants KCNJ11/ABCC8, TCF7L2 and CYP2C9. The response to metformin treatment was associated with the genetic variants ATM and SLC47A1. The response to treatment with glitazones was associated with the genetic variant PPARG. The therapeutic response to the treatment with gliptins was associated with the genetic variants TCF7L2 and CTRB1/2. It may be expected that in the near future pharmacogenetic knowledge will also be used within personalized treatment of type 2 diabetes. PMID- 27180667 TI - [Cholesterol metabolism in patients with type 2 diabetes]. AB - Diabetic dyslipidemia is a complex disorder associated with changes in lipid metabolism, which must be considered during care of the diabetic patient. Type 2 diabetes mellitus is a disease associated with a number of macrovascular and microvascular complications and it is necessary to treat the patient with regard to the possibility of developing these disorders. Prevention of cardiovascular complications is one of the most important factors of diabetes care, because cardiovascular diseases are among the leading causes of morbidity and mortality in patients with diabetes mellitus. The risk of developing atherosclerotic changes is significantly higher in diabetics in comparison with people without diabetes, which is mostly due to the differences in the plasma lipid metabolism and development of typical diabetic dyslipidemia with high atherogenic potential. Treatment of diabetic dyslipidemia as well as prevention of cardiovascular events is based on adherence to lifestyle changes, that have a positive effect on diabetes itself, and a suitable pharmacotherapy selected to achieve target plasma lipoprotein levels while affecting their quality. PMID- 27180668 TI - [Victoza changes diabetes and lives of patients 5 years already]. AB - Victoza (liraglutide) is a modern antidiabetic drug of GLP1 (glucagone like peptide) analogue group; since 2009 registered in Czech republic. VICTOZA is used in therapy of type 2 diabetic patients with preserved endougenous insulin secretion, usually in combination with other peroral antidiabetic drugs or with basal insulin. VICTOZA is applied once a day subcutaneously. The characteristical antidiabetic effect with beta cell protection is enhanced with supportive weigth reduction effect. Positive cardiovascular influence is expected, however data from recent studies are not available at this time. In clinical practice, the mild upper dyspepsia after initiation of therapy is the most common side effect, usually subsiding in several days. Alltogether, VICTOZA is a well tolerated antidiabetic medication decreasing glycated hemoglobin up to 15 mmol/l with minimal risk of hypoglycaemia. PMID- 27180669 TI - [XIGDUO - fixed combination of the active ingredients dapagliflozin and metformin]. AB - Fixed dose combination of two different drugs in the same or related indications are successfully used in various medical fields including diabetology. This article deals with the combination therapy comprising metformin and dapagliflozin in a single preparation, molecules affecting different pathophysiological mechanisms of type 2 diabetes, particularly insulin resistance and increased glucose reabsorption in the kidney. Most patients with type 2 diabetes does not achieve target glycemic control when treated with single antidiabetics and need for proper control of diabetes combination of several different drugs. Using the fixed combination leads to improved patients adherence and utilization of the full therapeutic potential of selected drugs. PMID- 27180670 TI - [Diabetes mellitus and pancreas cancer]. AB - Diabetes mellitus and pancreatic cancer establish both-side relationship, one disease may have influence a development of the other. Pathogenic mechanisms sharing their relationship are overviewed. Early diagnosis may contribute to better prognosis of the patients with malign tumor. The treatment by antidiabetic drugs offer to diabetic patients different risks of pancreatic cancer but lots of data are still lacking. PMID- 27180671 TI - [Early detection of ISHD in diabetic patients and determining the type of treatment]. AB - Diabetes mellitus is a major risk factor for the development of ischemic heart disease. Its prevalence in diabetic patients is reported to range broadly between 10-55 %. It is necessary to actively search for the presence of myocardial ischemia in patients with diabetes, since waiting for the development of symptoms is associated with the finding of already advanced coronary atherosclerosis in these patients, with less satisfactory outcomes of coronary interventions and surgery. Results of the BARDOT study seem to indicate that the appropriate tool for stratification of the risk of cardiac events in diabetics could be stress myocardial scintigraphy. This test is successful in detecting the presence of myocardial ischemia, assessing its size and location and identifying whether reversible ischemia is involved. Such data is very important with regard to choosing the right treatment strategy. We often find advanced coronary atherosclerosis in diabetic patients for which surgical treatment is more appropriate. Nonetheless in the era of modern stents also the patients with diabetes can be treated with intervention. All the influenceable risk factors for ischemic heart disease should be consistently treated by intervention in each diabetic patient, who should be given optimum pharmacotherapy. This involves medication with a proven impact on the patient prognosis, influencing the progression of coronary atherosclerosis and mitigation of myocardial ischemia. PMID- 27180672 TI - [What is the significance of the phenomenon of hypertension in disguise in patients with type 2 diabetes mellitus treated for long-lasting hypertension?]. AB - "Hypertension in disguise" is quite frequent in the patients with diabetes mellitus. It leads to organ damage similarly as persistent hypertension and it is associated with an increased cardiovascular risk which can be reduced through effective treatment. Persistent hypertension is present in 70% of the patients with type 2 diabetes mellitus. During its treatment, the picture of "masked hypertension" may be imitated (normalized blood pressure taken at a day clinic, as opposed to the increased values outside of it). This finding occurs in 35-60 % of the patients with type 2 diabetes mellitus and it is associated with the significance of changes to internal organs. The importance of this finding has been under discussion. PMID- 27180673 TI - [Management of type 2 diabetes mellitus therapy in a mature age]. AB - Type 2 diabetes mellitus represents a serious medical, social and economic problem, since it has become a pandemic in recent years, affecting up to 1/3 of the Czech population in old age. It is the clinically most significant metabolic disease in older age. A pharmacotherapeutic approach needs to be adjusted to the presence of multiple comorbidities in the elderly and to the patients ability to cooperate with treatment, and owing to the feared hypoglycemia which may contribute to increased morbidity, it detracts from the quality of life and limits the possibilities of treatment in many cases. When taking decisions about the treatment, the recommendations categorizing diabetic patients from the geriatric perspective as fit or fragile should be taken into account. The target values of diabetes compensation are derived from them. The purpose of the paper is to describe the possibilities of safe therapy for type 2 diabetes mellitus in older patients and draw attention to the risks that some types of treatment may present for older people. PMID- 27180674 TI - [Motor vehicle driving and diabetes mellitus - medical aspects]. AB - Diabetes mellitus is a disease which may affect the eligibility to hold a driving license and increase the risk of a road accident. Hypoglycemia while driving is considered to be the most risky situation, with diabetes increasing the mentioned risk for instance due to impaired vision in the case of possible retinopathy. The group of drivers with diabetes being at the greatest risk as to accidents are those with a case history of severe hypoglycemia or hypoglycemia occurred while driving, or possibly of a road accident. Measuring glycaemia before driving and their knowledge how to prevent and treat hypoglycemia - those are the two crucial preventive elements indispensable for insulin treated diabetes patients in order to secure safe road traffic. PMID- 27180675 TI - [Motor vehicle driving and not only diabetes mellitus - certain aspects of the legislations in the Czech Republic]. AB - A review of medical fitness to hold a drivers license in diabetes mellitus patients occurs when applying for the license and then at least every three years. Severe hypoglycemic events are an important criterion with the view of eligibility loss to drive a vehicle. All physicians regardless of their speciality who suspect the loss of eligibility in a patient they come into professional contact with are under the obligation to report this fact to the local authority in the patients place of residence. PMID- 27180676 TI - ["Healthy behaviour" and mental resilience in youth within the Diateens project]. AB - Approximately every fifth Slovak is obese and every other is overweight. These findings gave birth to a project called Diateens-the youth-oriented project aimed at the prevention of diabetes mellitus. The patronage over the project as one of the educational programme within the National Diabetes Programme, was assumed by the Slovak Diabetes Society and the Slovak WHO Office. The purpose of the project was to improve the awareness of young people about diabetes mellitus, ascertain the general state of their health and support a healthy lifestyle (healthy behavior) as an important component in the prevention of the disease. PMID- 27180677 TI - DsRNA-mediated targeting of ribosomal transcripts RPS6 and RPL26 induces long lasting and significant reductions in fecundity of the vector Aedes aegypti. AB - Ribosomal transcripts produce critical proteins that are involved in most cellular production processes. Targeting ribosomal transcripts has produced mortality in mites and ticks but the effect of ribosomal transcript knockdown has not been thoroughly examined in mosquitoes. We examine the effects of triggers targeting four ribosomal proteins (RP) transcripts. Although no significant mortality was observed after dsRNA microinjection and subsequent blood feeding, significant contrasts were observed on fecundity. Triggers targeting RPS6 and RPL26 effectively reduced gene expression but more importantly, reduced reproductive output by more than 96% and 91% at the first oviposition while triggers targeting RPL1 and RPS2 did not cause a reduction although gene expression was reduced. Significantly reduced fecundity continued through a second oviposition cycle in dsRPS6 and dsRPL26 cohorts, although the effect was not as strong. Relative gene expression levels confirmed specific transcript knockdown up to 20days post-injection in mosquitoes that did not oviposit or produced reduced clutch sizes. Dissections at 36h post-blood meal indicated defects in oocyte provisioning. The strong phenotype produced by dsRPS6 allowed us to examine the effects in various tissues as well as the dose response, trigger format, delivery method and trigger specificity in Aedes aegypti. Strong knockdown was observed in the abdomen and the ovaries. Greater than 50ng of dsRPS6 significantly reduced fecundity but not when delivered in a sugar meal or as an siRNA. Similar bioassays with mutated dsRPS6 triggers indicates that up to three mismatches per possible siRNA are still effective in reducing fecundity. These studies indicate that while active and effective triggers can be developed for vector species, the lack of an efficient delivery method is the biggest barrier to use as a potential control method. PMID- 27180679 TI - Regioselective carboannulation of electron-deficient allenes with dialkyl (2 formylphenyl)malonates leading to multisubstituted naphthalenes. AB - An efficient base-catalysed regioselective carboannulation of allenoates (or allenylphosphonates) with dialkyl 2-(2-formylphenyl)malonates that leads to multi substituted naphthalenes in high yields has been developed. This cascade reaction proceeds through Michael addition, cyclisation, dealkoxycarboxylation and tautomerisation. By using an allenylphosphine oxide, a species analogous to one of the intermediate species in the mechanistic pathway has been isolated. PMID- 27180678 TI - Diabetes mellitus is an independent risk factor for atrial fibrillation in a general Chinese population. AB - AIMS/INTRODUCTION: To explore the association between atrial fibrillation (AF) and diabetes mellitus in a general Chinese population, and the influence of hypertension. MATERIALS AND METHODS: From January 2013 to August 2013, we carried out a cross-sectional study involving 11,956 permanent residents aged >=35 years from the general population in the Liaoning province of China (response rate 85.3%). Each participant completed a questionnaire, had a physical examination, and underwent an electrocardiogram and echocardiogram. AF was diagnosed on the basis of the electrocardiogram findings. Logistic regression analyses were carried out to estimate the associations between diabetes mellitus and AF. The associations were also analyzed in hypertensive and normotensive subgroups. RESULTS: There was a higher prevalence of AF in participants with diabetes mellitus than those without diabetes mellitus (1.2 vs 0.5%; P = 0.004). In the hypertensive subgroup, the prevalence of AF in participants with diabetes mellitus was significantly higher than in participants without diabetes mellitus (1.5 vs 0.6%; P = 0.008); however, the prevalences were similar in the normotensive subgroup (0.3 vs 0.4%; P = 1.000). Similar trends were present in both men and women. After adjustment for cardiovascular risk factors, the independent association between diabetes mellitus and AF remained in the total sample (odds ratio 2.33, 95% confidence interval 1.20-4.54) and hypertensive subgroup (odds ratio 3.15, 95% confidence interval 1.52-6.56), but not in the normotensive subgroup (odds ratio 0.64, 95% confidence interval 0.08-5.31). CONCLUSIONS: Diabetes mellitus is an independent risk factor for AF in the general population in China, this association was present in total and hypertensive participants, but not in normotensive participants. PMID- 27180682 TI - Leveraging Health IT to Reduce Disparities in Three Underserved Beacon Communities. AB - Using health information technology (IT) can potentially address health disparities by increasing access to care, delivering higher-quality care, improving patient-provider communication, and enhancing patient safety. It describes challenges encountered by three underserved Beacon Communities that implemented health IT interventions, including inadequate connectivity infrastructure, technical support, expertise, and financial resources; provider shortages and staff turnover; and equipment theft. PMID- 27180680 TI - Acute dairy milk ingestion does not improve nitric oxide-dependent vasodilation in the cutaneous microcirculation. AB - In epidemiological studies, chronic dairy milk consumption is associated with improved vascular health and reduced age-related increases in blood pressure. Although milk protein supplementation augments conduit artery flow-mediated dilation, whether or not acute dairy milk intake may improve microvascular function remains unclear. We hypothesised that dairy milk would increase direct measurement of endothelial nitric oxide (NO)-dependent cutaneous vasodilation in response to local skin heating. Eleven men and women (61 (sem 2) years) ingested two or four servings (473 and 946 ml) of 1 % dairy milk or a rice beverage on each of 4 separate study days. In a subset of five subjects, an additional protocol was completed after 473 ml of water ingestion. Once a stable blood flow occurred, 15 mm-N G -nitro-l-arginine methyl ester was perfused (intradermal microdialysis) to quantify NO-dependent vasodilation. Red-blood-cell flux (RBF) was measured by laser-Doppler flowmetry, and cutaneous vascular conductance (CVC=RBF/mean arterial pressure) was calculated and normalised to maximum (%CVCmax; 28 mm-sodium nitroprusside). Full expression of cutaneous vasodilation was not different among dairy milk, rice beverage and water, and there was no effect of serving size on the total vasodilatory response. Contrary to our hypothesis, NO-dependent vasodilation was lower for dairy milk than rice beverage (D: 49 (sem 5), R: 55 (sem 5) %CVCmax; P<0.01). Acute dairy milk ingestion does not augment NO-dependent vasodilation in the cutaneous microcirculation compared with a rice beverage control. PMID- 27180681 TI - Cancer-associated DDX3X mutations drive stress granule assembly and impair global translation. AB - DDX3X is a DEAD-box RNA helicase that has been implicated in multiple aspects of RNA metabolism including translation initiation and the assembly of stress granules (SGs). Recent genomic studies have reported recurrent DDX3X mutations in numerous tumors including medulloblastoma (MB), but the physiological impact of these mutations is poorly understood. Here we show that a consistent feature of MB-associated mutations is SG hyper-assembly and concomitant translation impairment. We used CLIP-seq to obtain a comprehensive assessment of DDX3X binding targets and ribosome profiling for high-resolution assessment of global translation. Surprisingly, mutant DDX3X expression caused broad inhibition of translation that impacted DDX3X targeted and non-targeted mRNAs alike. Assessment of translation efficiency with single-cell resolution revealed that SG hyper assembly correlated precisely with impaired global translation. SG hyper-assembly and translation impairment driven by mutant DDX3X were rescued by a genetic approach that limited SG assembly and by deletion of the N-terminal low complexity domain within DDX3X. Thus, in addition to a primary defect at the level of translation initiation caused by DDX3X mutation, SG assembly itself contributes to global translation inhibition. This work provides mechanistic insights into the consequences of cancer-related DDX3X mutations, suggesting that globally reduced translation may provide a context-dependent survival advantage that must be considered as a possible contributor to tumorigenesis. PMID- 27180683 TI - Gender-affirming Surgeries in the Era of Insurance Coverage: Developing a Framework for Psychosocial Support and Care Navigation in the Perioperative Period. AB - Transgender people have a gender identity different from their birth-assigned sex. Transgender people may seek gender-affirming surgeries to align their body with their identified gender. With increasing visibility of transgender identities, and recognition of the importance of gender-affirming care, has come a policy shift toward mandated coverage or provision of blanket exclusions of these procedures by insurance companies and Medicaid. The World Professional Association for Transgender Health provides guidance to mental health professionals evaluating patients for gender-affirming surgeries, including making a diagnosis and assessing for capacity to consent. However the expansion of covered gender-affirming surgeries to safety-net populations has highlighted the need for an expanded presurgical process which includes a psychosocial assessment and care navigation. The proposed framework expands the preoperative assessment to include these components, and can be used to guide both health systems and insurance providers in the development of transgender medicine programs. PMID- 27180684 TI - Reducing Health Care Disparities for Minority Women in the Era of the Affordable Care Act: Opportunities within Primary Care. AB - Despite improvements in overall health of the American population, disparities persist, particularly for minority women. The Affordable Care Act (ACA) offers the potential to reduce disparities through expanded insurance coverage, greater access to high-quality care, and bolstered prevention efforts in the context of new models of care such as the patient-centered medical home (PCMH). We use case studies representing three clinical conditions (breast cancer, HIV, and coronary heart disease) to present strategies for how a PCMH could reduce disparities for minority women. The case studies highlight the opportunity that further implementation of the ACA provides to improve screening, risk assessment, and prevention for a range of conditions that impact the health of minority women, as well as areas ripe for future investigation. PMID- 27180685 TI - Language Access and Health Equity: Changes under the Affordable Care Act. AB - Health disparities between English-proficient and limited English-proficient (LEP) groups in the United States have been widely documented. Provisions of the Affordable Care Act (ACA), including increased funding to community health centers and resources to help consumers who are purchasing Marketplace coverage afford new access to health care for speakers of languages other than English, which includes more than 60 million individuals, one-third of whom are LEP. This commentary discusses the legislative precedent for, successes of, and potential future directions for the implementation of the ACA as it relates to language access, health disparities, health equity, access to health care, and the linguistic needs of the LEP population in the United States. PMID- 27180687 TI - Community Health Workers' Palliative Care Learning Needs and Training: Results from a Partnership between a US University and a Rural Community Organization in Mpumalanga Province, South Africa. AB - The lack of palliative care knowledge among health care providers is a major barrier to adequate care in the rural provinces of South Africa (SA). Three aims: (1) to identify palliative care learning needs of community health workers (CHWs) working in a non-governmental organization (NGO) in Mpumalanga province SA, (2) to develop a training session based on the needs identified by the CHWs, and (3) to describe CHWs' perceptions of the usefulness of the training content. Data were collected from 29 CHWs in focus group interviews. Content analysis identified eight palliative care learning needs: HIV/AIDS, palliative care, TB, sexually-transmitted illnesses, debriefing, care of bedridden patients, other chronic diseases. Based on three of the most salient learning needs, a training session was planned and delivered. Future program development should consider interventions to provide emotional support for CHWs and how to evaluate the quality and impact of care provided on the community. PMID- 27180686 TI - Insurance Coverage for Rehabilitation Therapies and Association with Social Participation Outcomes among Low-Income Children. AB - OBJECTIVES: (1) To profile children's health insurance coverage rates for specific rehabilitation therapies; (2) to determine whether coverage for rehabilitation therapies is associated with social participation outcomes after adjusting for child and household characteristics; (3) to assess whether rehabilitation insurance differentially affects social participation of children with and without disabilities. METHODS: We conducted a cross-sectional analysis of secondary survey data on 756 children (ages 3-17) from 370 households living in low-income neighborhoods in a Midwestern U.S. city. Multivariate mixed effects logistic regression models were estimated. RESULTS: Significantly higher proportions of children with disabilities had coverage for physical therapy, occupational therapy, and speech and language pathology, yet gaps in coverage were noted. Multivariate analysis indicated that rehabilitation insurance coverage was significantly associated with social participation (OR = 1.67, 95% CI: 1.013-2.75). This trend was sustained in subgroup analysis. CONCLUSIONS: Findings support the need for comprehensive coverage of all essential services under children's health insurance programs. PMID- 27180688 TI - Public Dental Safety Net in Iowa: Capacity and Readiness for Health Care Reform. AB - OBJECTIVE: Examine the current capacity of Iowa's public dental safety net and organizational readiness for implementation of the Affordable Care Act (ACA). METHODS: We surveyed Iowa Community Health Center (CHC) dental clinics for factors related to clinic capacity and organizational readiness for ACA-related change. RESULTS: With 14 clinics (93%) responding, clinics had means of 13,064 patient visits and 23% broken appointments in 2012. Seventy percent of clinics reported high confidence in their ability to respond to changes associated with health care reform. However, over 60% agreed that current circumstances limited their ability to respond to these challenges. CONCLUSIONS: CHC dental clinics in Iowa understand ACA-related changes regarding their patient population, but are limited in their ability make needed changes in response to increased demand. This may affect the clinics' transition into an environment with increased demand for dental services as a result of Medicaid expansion in Iowa. PMID- 27180690 TI - Patient Experience Of Provider Refusal Of Medicaid Coverage And Its Implications. AB - Previous studies show that many physicians do not accept new patients with Medicaid coverage, but no study has examined Medicaid enrollees' actual experience of provider refusal of their coverage and its implications. Using the 2012 National Health Interview Survey, we estimate provider refusal of health insurance coverage reported by 23,992 adults with continuous coverage for the past 12 months. We find that among Medicaid enrollees, 6.73% reported their coverage being refused by a provider in 2012, a rate higher than that in Medicare and private insurance by 4.07 (p<.01) and 3.68 (p<.001) percentage points, respectively. Refusal of Medicaid coverage is associated with delaying needed care, using emergency room (ER) as a usual source of care, and perceiving current coverage as worse than last year. In view of the Affordable Care Act's (ACA) Medicaid expansion, future studies should continue monitoring enrollees' experience of coverage refusal. PMID- 27180691 TI - Enhancing Adolescent Reproductive Health Services: Assessment of Health Care Practices in Holyoke and Springfield, MA Engaged in the Youth First Initiative. AB - Health care practices can play a key role in reducing teen pregnancies, though current health care systems do not adequately meet adolescents' reproductive health needs. To address this gap, Youth First, a Centers for Disease Control and Prevention funded, community-wide initiative in Holyoke and Springfield (Massachusetts) established partnerships with nine local health care practices to increase adolescent access to health services. However, we had limited knowledge about their reproductive health services and policies. To address this gap, assessments were conducted with staff using structured interviews and surveys to inform targeted efforts to enhance the quality and youth friendliness of adolescent reproductive health services. Findings revealed that many of the youth friendly services best practices recommended by the CDC were not routinely implemented by all health care practices. Findings from this assessment can be used to support health care practices to facilitate widespread adoption of best practices related to meeting adolescents' reproductive health needs. PMID- 27180689 TI - Development of a Practical Model for Targeting Patient Decision Support Interventions to Promote Colorectal Cancer Screening in Vulnerable Populations. AB - We sought to develop a practical model for predicting probability of colorectal cancer (CRC) screening completion in a diverse safety-net population and a subsequent framework for targeting screening promotion interventions. Data used to construct the models was prospectively collected from a CRC screening intervention. Models were cross-validated by randomly splitting the data into training and validation samples. The predicted probabilities of screening completion from the final model were trichotomized into framework groups and cross-validated by defining cut-points in the training sample, applying them to the validation sample, and comparing across samples for homogeneity. The final model included demographic and simple psychosocial measures and predicted screening behavior adequately (AUROC=0.63). The framework groups (cut-points 0.62 (low), 0.74 (medium), and 1.0 (high)) were homogeneous across the two samples. The model and framework may be useful for designing and delivering targeted interventions to promote CRC screening. Future research should validate the framework groups. PMID- 27180692 TI - Measuring the Integration of Tobacco Policy and Treatment into the Behavioral Health Care Delivery System: How Are We Doing? AB - People with a mental illness and/or drug use disorder have a higher rate of smoking than adults in general. To address this challenge, recommendations include integrating tobacco-free policies and tobacco dependency treatment into the behavioral health care delivery system. Currently, little is known regarding levels of such integration. A 65-item Internet survey measuring integration assessed three areas: a) policies addressing the use of tobacco products; b) provision of evidence-based tobacco dependence treatment; and, c) capacity to help employees/volunteers quit tobacco use. The survey was distributed to representatives of all behavioral health programs in Wisconsin. The survey response rate was 27.1%. Programs, on average, were 40% integrated. A significant proportion of programs (20%) were less than 20% integrated. A few programs (4.3%) exceeded 80% integration. Integration of tobacco policies and treatment into the behavioral health care delivery system remains limited and there is a need for technical assistance and training. PMID- 27180694 TI - Perceptions of Physical Inspections as a Tool to Protect Housing Quality and Promote Health Equity. AB - Physical inspections that assess how well affordable housing properties meet quality and safety standards help to ensure that low-income tenants live in a healthy built environment. This study was part of a larger Health Impact Assessment (HIA) conducted between January 2012 and November 2013 to inform policymakers about the potential health consequences of a proposed policy decision to align the physical inspections required by housing funding agencies, which would result in a reduction of the frequency of physical inspections. Key informant interviews (n=18) of property managers and tenants were used to explore the inspection process, identification of housing quality issues, and potential effects on the health of affordable housing tenants and the impact on property management practices. Results indicate that physical inspection frequency may be an important trigger for property managers and tenants to adhere to proper maintenance schedules. PMID- 27180693 TI - Lessons Learned from Three Models that Use Small Grants for Building Academic Community Partnerships for Research. AB - Despite the direct contribution of community-engaged research towards effective translation, establishing strong and sustained community academic research partnerships remains a challenge. The Atlanta Clinical and Translational Science Institute's Community Engagement Research Program (CERP) has developed and implemented three models for using small grants to seed new community academic partnerships for research: 1) community-initiated health projects with faculty partners, 2) dissemination of discoveries to community partners, and 3) building collaborative research capacity. In this paper, we describe each model in terms of its purpose, funding level, funding period, proposal requirements, selection criteria and faculty involvement. Resulting partnerships are described, along with benefits and challenges from faculty and community perspectives, and lessons learned in using these mechanisms to promote community-engaged research. These models may aid others attempting to promote community-engaged research for the purpose of narrowing the gap between research, practice and ultimately, impact on community health. PMID- 27180695 TI - Hearing the Community: Evolution of a Nutrition and Physical Activity Program for African American Women to Improve Weight. AB - Listening to the needs of the community is an important step toward reducing health disparities. Researchers may need to adjust their methods to maximize participation and benefit to the community. This report describes how the project team adjusted its approach to a weight loss intervention to support a community of African American women seeking to improve their health. PMID- 27180696 TI - Mujer Sana, Familia Fuerte: The Effects of a Culturally-Relevant, Community Based, Promotores Program to Increase Cervical Cancer Screening among Latinas. AB - OBJECTIVE: Although cervical cancer can be prevented through screening and follow up, Latinas' rate of Pap tests remains low due to knowledge gaps and cultural and attitudinal factors. METHODS: This study used a single-group pre-/post-test design to evaluate the effectiveness of Mujer Sana, Familia Fuerte (Healthy Woman, Strong Family), an intervention intended to improve Latinas' cervical cancer prevention knowledge, attitudes, self-efficacy to obtain a Pap test, and intention to get tested. The intervention is delivered through a single session by promotores de salud, who use a culturally competent, linguistically appropriate toolkit. A total of 5,211 Latinas participated in the study. RESULTS: The evaluation indicated that participants had increases in knowledge, positive attitudes, self-efficacy, and intention to test. CONCLUSION: Latinas have a low rate of cervical cancer screening but a high rate of cervical cancer, and Mujer Sana, Familia Fuerte shows promise as a public health practice for use with this population. PMID- 27180698 TI - Age Influences the Effects of Provider Racial Biases on Treatment Adherence and Blood Pressure Control for African American Hypertensive Patients. AB - OBJECTIVE: The purpose of the current study was to investigate age as a moderator of the effects of perceived provider racial biases on treatment adherence and blood pressure control for African American hypertensive patients. METHODS: One hundred-eighty patients were recruited from an outpatient medical clinic in the Southeastern region of the U.S. Moderated regression analyses and multinomial logistic analyses were used to test the study hypotheses. RESULTS: Findings revealed that age significantly moderated the effects of perceived provider biases on treatment adherence, such that older patients exhibited lower scores for treatment adherence in relation to exposure to provider biases. Logistic analyses revealed that older patients exhibited significantly greater probabilities for higher systolic blood pressure in relation to perceived provider biases. CONCLUSIONS: The findings suggest that subjective appraisal of exposure to provider racial biases is associated with adverse treatment adherence and blood pressure control for older African American hypertensive patients. PMID- 27180697 TI - In their Own Words: Resilience among Haitian Survivors of the 2010 Earthquake. AB - Social sciences literature highlights the importance of resilience in relation to risk and trauma. The 2010 Haitian earthquake compounded trauma for a nation that has endured slavery/despotic leadership, structural violence and poverty. Since 2010, various sources broadly describe Haitian survivors as resilient. We reviewed definitions of resilience published between 1990 and 2013, comparing them with perspectives of earthquake survivors from economically diverse communities in Haiti who, participated in semi-structured interviews (n=38) and in six focus groups (n=63) between 2010-2011. Haitian resilience accords with some definitions from the literature. It also comprises independent, discrete, and isolated contextual resignation and intentional choice to survive and function-when there is no alternative course of action. Understanding Haitian resilience, can inform health/mental health and policy interventions, if these are taken as cultural resources. Intervention efforts should incorporate survivors' input as key informants on what constitute resilience and reconstruction goals for them. PMID- 27180699 TI - 'Our only resource': Perspectives and Recommendations of Rural African American Youth on Adapting Sexual Health and Risk Reduction Interventions. AB - Recent studies have documented disproportionately high rates of sexually transmitted infections (STIs), HIV, and births among adolescents in rural areas of the United States. Despite this, the majority of sexual health education programs and interventions were developed for adolescents in metropolitan areas, and may not be appropriate or relevant for rural youth. The present study investigates the perspectives of 73 African American youth in rural Georgia who participated in a cognitive-behavioral intervention to reduce sexual risk behaviors, in an effort to understand how the intervention and ones similar to it may be tailored to better meet the needs of rural adolescents. Findings highlight the importance of incorporating diverse teaching and recruitment strategies into interventions when delivering them to rural youth, as well as the need to expand education and risk reduction efforts. Additional research is warranted to understand better how to meet the sexual health education needs of rural youth. PMID- 27180700 TI - Predictors of Pain Management among American Indian Cancer Survivors. AB - There is little research on cancer symptom management among Indigenous populations. This paper reports on the predictors of cancer pain management among American Indian cancer patients/survivors and their caregivers/family. The intervention was a symptom management toolkit delivered via traditional talking circles vs. standard care (control) at eight randomized reservation and urban clinic sites in the Southwest. Participants (N=184) were American Indian adults diagnosed with cancer and/or caregiver/family members. The primary outcome measure collected via pre-test and post-test questionnaires was the ability to manage cancer pain. Significant differences at post-test were the ability to manage cancer-related pain (p=.02) and a close relationship (p=.0018) that proved significant for intervention participants and was instrumental in fostering their ability to manage pain. The study also showed improvement in the desire and ability to improve cancer pain management among intervention participants. Programs targeting American Indians should use culturally appropriate education to improve management of cancer-related symptoms. PMID- 27180701 TI - Bone Mineral Density in Navajo Men and Women and Comparison to Non-Hispanic Whites from NHANES (2005-2008). AB - PURPOSE: To describe bone mineral density (BMD) at the hip and spine and prevalence of low bone mass and osteoporosis in Navajo men and women across age, gender, and body mass index (BMI) compared with non-Hispanic (NH) Whites from NHANES (2005-2008). METHODS: Cross-sectional dual energy x-ray absorptiometry measurements at the hip and spine in 1,097 participants from the Education and Research Towards Health study. RESULTS: Bone mineral density was lower among younger Navajo than NH-Whites at lower BMI, and in overweight, younger men at lumbar spine and total hip. Spine BMD was lower in Navajo women, across BMI. Prevalence of low bone mass and osteoporosis in Navajo was higher than NH-Whites, particularly among women. CONCLUSIONS: Further research is needed to understand if lower BMD among younger Navajo signals a risk for future fracture, and fracture risk relative to BMD, given the challenges in health care access and fracture morbidity among minorities. PMID- 27180702 TI - Measuring Geographic "Hot Spots" of Racial/Ethnic Disparities: An Application to Mental Health Care. AB - This article identifies geographic "hot spots" of racial/ethnic disparities in mental health care access. Using data from the 2001-2003 Collaborative Psychiatric Epidemiology Surveys(CPES), we identified metropolitan statistical areas(MSAs) with the largest mental health care access disparities ("hot spots") as well as areas without disparities ("cold spots"). Racial/ethnic disparities were identified after adjustment for clinical need. Richmond, Virginia and Columbus, Georgia were found to be hot spots for Black-White disparities, regardless of method used. Fresno, California and Dallas, Texas were ranked as having the highest Latino-White disparities and Riverside, California and Houston, Texas consistently ranked high in Asian-White mental health care disparities across different methods. We recommend that institutions and government agencies in these "hot spot" areas work together to address key mechanisms underlying these disparities. We discuss the potential and limitations of these methods as tools for understanding health care disparities in other contexts. PMID- 27180703 TI - Physical Activity of Mexican-origin Children: Examining Parental Support. AB - Objectives Mexican-origin children living along the US-Mexico border in colonias communities are medically underserved, at great risk for obesity-related diseases, and rarely meet physical activity guidelines. This study examined the roles of parental social support and social norms for physical activity among these children. METHODS: Promotora-researchers conducted one-on-one interview administered surveys with 99 Mexican-origin mother-child dyads (n=198). Survey items examined perceptions of familial social support and norms relating to physical activity. RESULTS: Parental social support for physical activity received by children was low, and gender differences were detected. Discrepancies between mother and child perceptions were also detected. CONCLUSIONS: High rates of overweight and obesity and low familial social support indicate a need for improved parental social support to increase physical activity levels and combat obesity among underserved Mexican-origin children residing in Texas border colonias. PMID- 27180704 TI - Neighborhoods, Social and Cultural Correlates of Obesity Risk among Latinos living on the U.S.-Mexico border in Southern California. AB - OBJECTIVES: We explored the relationship between obesity and neighborhood related, social, and cultural variables and possible moderation by acculturation and cross-national practices. METHODS: We obtained data from the 2009 San Diego Prevention Research Center's community survey, which used multistage sampling methods to recruit 397 adult respondents and conducted multilevel logistic analytic methods. RESULTS: Nearly half of the respondents were obese. Respondents had low acculturation scores and reported crossing the U.S.-Mexico border about three times per month, mostly to visit family and friends. Neighborhoods where respondents lived were predominantly Latino and had 27% home ownership. A significant cross-level interaction emerged: those who reported crossing the border and reported higher levels of collective efficacy were more likely to be obese than those who had not crossed. CONCLUSIONS: Study findings provide evidence of the complex relationship among obesity risk factors in a U.S.-Mexico border community that warrant further examination to prevent and control obesity. PMID- 27180705 TI - Building a "Deep Fund of Good Will": Reframing Research Engagement. AB - BACKGROUND: The engagement of underrepresented populations in health research has been an ongoing challenge. Yet, the participation of these groups is recognized as key to health equity. METHODS: Semi-structured interviews with 31 experienced investigators successful in the recruitment of underrepresented minorities were analyzed with reference to the concept of social capital to determine: 1) if it is actually in use by successful researchers although yet unidentified as such; and 2) if the rubric could shed light on new directions especially for those who find it difficult to implement community-engaged recruitment methods systematically. RESULTS: Findings indicate that some elements of the concept of social capital are being used successfully, but that there are also substantial barriers to its full implementation. CONCLUSION: A lack of enforceable trust and associated institutional support for researchers is a detriment to research engagement. Efforts to remedy this would benefit large research projects, including clinical trials. PMID- 27180706 TI - Racial Health Disparities, and Variant Red Cell and Iron Homeostasis. AB - Oxidative stress from excess iron may contribute to racial health disparities. Previously we reported improved clinical outcomes with lower ferritin and higher percent transferrin saturation (%TS) levels in White but not Black participants with peripheral arterial disease entered to a clinical trial. This report demonstrates racially variant interactions between hemoglobin, ferritin, and %TS levels. Lower hemoglobin and %TS levels, and higher ferritin levels were documented in Black compared with White participants within cardiovascular disease risk categories. Ferritin levels near 80 ng/mL related to higher hemoglobin levels in White but not Black participants. Higher %TS levels with ferritin levels above 80 ng/mL in White participants were blunted in Black participants. Ferritin/%TS ratios were significantly higher in Black than White participants. Iron incorporation into hemoglobin and scavenging by transferrin may buffer iron toxicity more effectively in White than in Black individuals. Metabolic vulnerability to iron excess may explain, in part, racial health disparities. PMID- 27180707 TI - Perceived Interest in Vasectomy among Latina Women and their Partners in a Community with Limited Access to Female Sterilization. AB - The low prevalence of vasectomy among Latino men in the United States is often attributed to cultural characteristics despite limited evidence supporting this hypothesis. We assessed male partners' perceived willingness to undergo vasectomy through surveys with 470 Mexican-origin women who did not want more children in El Paso, Texas. Overall, 32% of women reported that their partner would be interested in getting a vasectomy. In multivariable analysis, completing high school (OR=2.03 [1.05, 3.95]), having some college education (OR=2.97 [1.36, 6.48]) or receiving US government assistance (OR=1.95 [1.1, 3.45]) was associated with partners' perceived interest. Additionally, we conducted two focus groups on men's knowledge and attitudes about vasectomy with partners of a subsample of these women. Despite some misperceptions, male partners were willing to get a vasectomy, but were concerned about cost and taking time off work to recover. Health education and affordable vasectomy services could increase vasectomy use among Mexican-origin men. PMID- 27180708 TI - The health of U.S. agricultural worker families: A descriptive study of over 790,000 migratory and seasonal agricultural workers and dependents. AB - Migratory and seasonal agricultural workers (MSAWs) are a historically under served population that experience poor access to health care. The aim of this study was to describe the demographic, socioeconomic, and health status of U.S. agricultural workers and their dependents who were patients of a Migrant Health Center in 2012. The authors used the Uniform Data System to examine demographic, socioeconomic, and health variables for 793,188 patients of 164 Migrant Health Centers during 2012. Means, proportions, and period prevalence was calculated for all variables. Results showed that 80% of MSAWs earned family incomes below 100% of federal poverty level. Among the reported diagnoses, the most common were hypertension, diabetes mellitus, and mental health conditions. Fifty-three percent of all MSAWs and 71% of adult MSAWs were uninsured, indicating that Migrants Health Centers continue to play a vital role in providing access to primary health care for MSAWs and their families. PMID- 27180709 TI - Understanding Pathways to Usual Source of Care among Asian Americans. AB - Although the prevailing conceptual model for health care access is the Andersen Behavioral Model of Health Service Use, researchers have not evaluated empirically whether model pathways are appropriate for Asian Americans (AAs). Using path analysis with 2009 California Health Interview Survey data, we tested pathways among predisposing, enabling, and need factors and acculturation factors for having a usual source of care (USC) among AA adults. Pathway differences among ethnic subgroups (Chinese, Koreans, and Vietnamese) were also examined. The model adequately predicted USC among AAs. As expected, insurance was the key predictor but higher education levels were associated with lower income and lower income with having a USC. English proficiency also contributed significantly to the AA model. Ethnic subgroup models varied significantly. Findings suggest that the Andersen behavioral model is appropriate for studying USC among AAs though pathways vary by ethnicity. Pathways for education and English proficiency must be better understood. PMID- 27180711 TI - Skin Disease in the Uninsured: Diagnoses, Management Decisions, and Referral Outcomes of an Urban Free Clinic. AB - An understanding of the burden of skin disease in the uninsured population is needed to address the unique barriers they face to access dermatologic care. We conducted a retrospective chart review of patients seen for skin conditions over three years at the New York City (NYC) Free Clinic, a weekly primary care clinic operated by the NYU School of Medicine and the Institute for Family Health. Main outcomes of this study were descriptive analyses of demographic characteristics, diagnoses, management strategies, and referral outcomes, as well as key factors influencing referral to a dermatologist and referral attendance. Diagnosis was a significant predictor of referral (p<.000). The referral attendance rate was 52.5%. Patients older than 50 years were more likely to attend their appointments than younger patients (p=.025). Gender, wait time, and travel distance had no significant association with non-attendance. While demand for dermatologic care by uninsured patients in NYC is high, referral non-attendance remains a substantial barrier to care. PMID- 27180710 TI - An Evaluation of the Ho'ouna Pono Curriculum: A Pilot Study of Culturally Grounded Substance Abuse Prevention for Rural Hawaiian Youth. AB - This pilot study evaluated the Ho'ouna Pono curriculum, which is a culturally grounded, school-based, drug prevention curriculum tailored to rural Native Hawaiian youth. The curriculum focuses on culturally relevant drug resistance skills training and is aligned with the State of Hawai'i academic standards. Six Hawai'i Island public middle/intermediate schools randomly assigned to intervention or treatment-as-usual comparison conditions (N = 213) were evaluated in this study. Paired sample t-tests separating intervention and comparison groups were conducted, as well as mixed models that adjusted for random effects (nesting) at the school level. Findings suggested that the curriculum was effective in maintaining youths' use of culturally relevant drug resistance skills, as well as decreasing girls' aggressive behaviors, at six-month follow up. Unanticipated findings also suggested areas for curricular improvement, including more emphasis on normative drug education. Implications for future research and development of the curriculum are discussed. PMID- 27180712 TI - Characteristics of Homeless Adults Who Died of Drug Overdose: A Retrospective Record Review. AB - Drug overdose is a major cause of death among homeless people, but little is known about the characteristics of homeless overdose decedents. We conducted a retrospective record review of 219 adult patients of Boston Health Care for the Homeless Program (BHCHP) who died of drug overdose in 2003-2008. We assessed the substances implicated in overdose and the health and service use characteristics of decedents prior to death. Eighty-one percent of overdose deaths involved opioids and 40% involved multiple drugs. Problem substance use (85%), psychiatric illness (61%), and chronic pain (45%) were common, and 32% had documentation of all three. Half were well-connected to BHCHP, and 35% had a clinic visit within 90 days of death. The complex health histories and frequent health care contacts of homeless drug overdose decedents suggest that clinical facilities may be an important frontline venue for overdose education, naloxone distribution, and integrated substance use treatment programming. PMID- 27180713 TI - Emergency Department Use for Dental Problems among Homeless Individuals: A Population-Based Cohort Study. AB - OBJECTIVES: To evaluate emergency department (ED) visits for dental problems among Toronto's homeless population (Ontario, Canada). METHODS: A random sample of 1,189 homeless was recruited from shelters and meal programs. Emergency department visits for non-traumatic dental problems (ICD-10-CA codes K00-K14) were identified using participants' health insurance number, during 2005-2009. Age- and sex-matched controls were selected from low-income neighborhoods. RESULTS: Homeless and matched controls had 182 and 10 ED visits for dental problems, respectively. Homeless people were more significantly more likely (OR=2.27, p=.007) to make ED visit for dental problems compared with controls. Over 80% of the ED visits by homeless people were for odontogenic infections, and 46% of homeless people had more than one such visit. CONCLUSION: The high rate of ED visits for dental problems by people who are homeless suggests that access to dental care is inadequate. The large number of repeat visits indicates that ED settings are ineffective for treatment of dental problems. PMID- 27180714 TI - The Intergenerational Transfer of Education Credentials and Health: Evidence from the 2008 General Social Survey-National Death Index. AB - BACKGROUND: The educational attainment of a parent is a powerful predictor of children's wellbeing, but little is known about why this is the case. METHODS: We used the 2008 General Social Survey to explore factors that may explain the relationship between one's father's education and one's own mortality. These include (1) intellectual traits, (2) material wellbeing, (3) psychological characteristics, (4) personality characteristics, and (5) social capital. RESULTS: The education credentials of one's father are significantly associated with one's risk of death. The strongest mediators are own educational attainment, family income, home ownership, and subjective socioeconomic status. To a lesser extent, respondents' happiness with friends and family and social bonding were also pathways. CONCLUSIONS: A father's educational attainment appears to influence his children's health, and may do so not only by improving the child's material circumstances but also through his or her educational attainment and other psychological and social characteristics. PMID- 27180716 TI - Characteristics and Likelihood of Ongoing Homelessness Among Unsheltered Veterans. AB - INTRODUCTION: Unsheltered homelessness is an important phenomenon yet difficult to study due to lack of data. The Veterans Health Administration administers a universal homelessness screener, which identifies housing status for Veterans screening positive for homelessness. METHODS: This study compared unsheltered and sheltered Veterans, assessed differences in rates of ongoing homelessness, and estimated a mixed-effect logistic regression model to examine the relationship between housing status and ongoing homelessness. RESULTS: Eleven percent of Veterans who screened positive for homelessness were unsheltered; 40% of those who rescreened were homeless six months later, compared with less than 20% of sheltered Veterans. Unsheltered Veterans were 2.7 times as likely to experience ongoing homelessness. DISCUSSION: Unsheltered Veterans differ from their sheltered counterparts-they are older, more likely to be male, less likely to have income-and may be good candidates for an intensive housing intervention. Future research will assess clinical characteristics and services utilization among this population. PMID- 27180718 TI - Erratum. PMID- 27180719 TI - Note from the Editor: Part 1: Health Policy and ProgramsPart 2: Racial and Ethnic Minority HealthPart 3: Epidemiology. PMID- 27180715 TI - Post-traumatic Stress Disorder Symptoms and Mental Health over Time among Low Income Women at Increased Risk of HIV in the U.S. AB - Women living in poverty suffer more post-traumatic stress disorder (PTSD) symptoms than do members of the general population; however we know little about factors associated with changes in their PTSD symptoms over time. Using data from HPTN 064, a cohort of women from low-income, high-HIV-prevalence communities across six eastern states (n=1,860), we assessed the prevalence of and changes in PTSD symptoms over 12 months and the effect of potential predictors on symptom acquisition and remission (via the Primary Care-PTSD symptoms scale). Forty-three percent screened positive for PTSD symptoms. Those reporting food insecurity, ongoing abuse, depressive symptoms, or binge drinking were more likely to acquire PTSD symptoms. Those with ongoing abuse or depressive symptoms were less likely to experience PTSD symptom remission. Findings suggest a need to integrate programs to reduce abuse, depression, and economic hardship with those that address sexual health risks among women living in low-income, high-HIV-prevalence neighborhoods. PMID- 27180720 TI - Sharing the Educational Wealth: A Nursing and Health Informatics Program Collaboration. PMID- 27180721 TI - Mixed-ligand copper(II) complexes activate aryl hydrocarbon receptor AhR and induce CYP1A genes expression in human hepatocytes and human cell lines. AB - The effects of four copper(II) mixed-ligand complexes [Cu(qui1)(L)]NO3.H2O (1-3) and [Cu(qui2)(phen)]NO3 (4), where qui1=2-phenyl-3-hydroxy-4(1H)-quinolinone, Hqui2=2-(4-amino-3,5-dichlorophenyl)-N-propyl-3-hydroxy-4(1H)-quinolinone-7 carboxamide, L=1,10-phenanthroline (phen) (1), 5-methyl-1,10-phenanthroline (mphen) (2), bathophenanthroline (bphen) (3), on transcriptional activities of steroid receptors, nuclear receptors and xenoreceptors have been studied. The complexes (1-4) did not influence basal or ligand-inducible activities of glucocorticoid receptor, androgen receptor, thyroid receptor, pregnane X receptor and vitamin D receptor, as revealed by gene reporter assays. The complexes 1 and 2 dose-dependently induced luciferase activity in stable gene reporter AZ-AhR cell line, and this induction was reverted by resveratrol, indicating involvement of aryl hydrocarbon receptor (AhR) in the process. The complexes 1, 2 and 3 induced CYP1A1 mRNA in LS180 cells and CYP1A1/CYP1A2 in human hepatocytes through AhR. Electrophoretic mobility shift assay EMSA showed that the complexes 1 and 2 transformed AhR in its DNA-binding form. Collectively, we demonstrate that the complexes 1 and 2 activate AhR and induce AhR-dependent genes in human hepatocytes and cancer cell lines. In conclusion, the data presented here might be of toxicological importance, regarding the multiple roles of AhR in human physiology and pathophysiology. PMID- 27180723 TI - Heterometallic trinuclear {CoLn(III)} (Ln = Gd, Tb, Ho and Er) complexes in a bent geometry. Field-induced single-ion magnetic behavior of the Er(III) and Tb(III) analogues. AB - Through the use of a multi-site compartmental ligand, 2-methoxy-6-[{2-(2 hydroxyethylamino)ethylimino}methyl]phenol (LH3), the family of heterometallic, trinuclear complexes of the formula [CoLn(L)2(MU-O2CCH3)2(H2O)3].NO3.xMeOH.yH2O has been expanded beyond Ln = Dy(III) to include Gd(III) (), Tb(III) (), Ho(III) () and Er(III) () for , and (x = 1; y = 1) and for (x = 0; y = 2). The metallic core of these complexes consists of a (Co(III)-Ln(III)-Co(III)) motif bridged in a bent geometry resulting in six-coordinated distorted Co(III) octahedra and nine coordinated Ln(III) monocapped square-antiprisms. The magnetic characterization of these compounds reveals the erbium and terbium analogues to display a field induced single-ion magnetic behavior similar to the dysprosium analogue but at lower temperatures. The energy barrier for the reversal of the magnetization of the CoTb(III) analogue is Ueff >= 15.6(4) K, while for the CoEr(III) analogue Ueff >= 9.9(8) K. The magnetic properties are discussed in terms of distortions of the 4f electron cloud. PMID- 27180722 TI - Marked variation between winter and spring gut microbiota in free-ranging Tibetan Macaques (Macaca thibetana). AB - Variation in the availability and distribution of food resources is a strong selective pressure on wild primates. We explored variation in Tibetan macaque gut microbiota composition during winter and spring seasons. Our results showed that gut microbial composition and diversity varied by season. In winter, the genus Succinivibrio, which promotes the digestion of cellulose and hemicellulose, was significantly increased. In spring, the abundance of the genus Prevotella, which is associated with digestion of carbohydrates and simple sugars, was significantly increased. PICRUSt analysis revealed that the predicted metagenomes related to the glycan biosynthesis and metabolic pathway was significantly increased in winter samples, which would aid in the digestion of glycan extracted from cellulose and hemicellulose. The predicted metagenomes related to carbohydrate and energy metabolic pathways were significantly increased in spring samples, which could facilitate a monkey's recovery from acute energy loss experienced during winter. We propose that shifts in the composition and function of the gut microbiota provide a buffer against seasonal fluctuations in energy and nutrient intake, thus enabling these primates to adapt to variations in food supply and quality. PMID- 27180724 TI - Juvenile hormone facilitates the antagonism between adult reproduction and diapause through the methoprene-tolerant gene in the female Colaphellus bowringi. AB - In insects, the process whereby juvenile hormone (JH) regulates short-day (SD) induced reproductive diapause has been previously investigated. However, we still do not understand the mechanism by which JH regulates long-day (LD)-induced reproductive diapause. In this study, we use a cabbage beetle, Colaphellus bowringi, which is a serious pest of cruciferous vegetables in Asia capable of entering reproductive diapause under LD conditions, as a model to test whether JH regulates female reproductive diapause similar to the mechanism of SD-induced diapause. Our results showed that the JH analog (JHA) methoprene significantly induced ovarian development but inhibited lipid accumulation of diapause-destined adults. Meanwhile, the transcripts of the vitellogenin (Vg) genes were upregulated, whereas the expression of the fat synthesis and stress tolerance genes were downregulated. RNA interference of the JH candidate receptor gene methoprene-tolerant (Met) blocked JH-induced ovarian development and Vg transcription, suggesting a positive regulatory function for JH-Met signaling in reproduction. Furthermore, under reproduction-inducing conditions, Met depletion promoted a diapause-like phenotype, including arrested ovarian development and increased lipid storage, and stimulated the expression of diapause-related genes involved in lipid synthesis and stress tolerance, suggesting JH-Met signaling plays an important role in the inhibition of diapause. Accordingly, our data indicate that JH acts through Met to facilitate development of the reproductive system by upregulating Vg expression while inhibiting diapause by suppressing lipid synthesis and stress tolerance in the cabbage beetle. Combined with previous studies in SD-induced reproductive diapause, we conclude that JH may regulate female reproductive diapause using a conserved Met-dependent pathway, regardless of the length of the photoperiod inducing diapause in insects. PMID- 27180725 TI - Ecdysteroid signalling components in metamorphosis and development of the desert locust, Schistocerca gregaria. AB - The arthropod-specific hormone family of ecdysteroids plays an important role in regulating diverse physiological processes, such as moulting and metamorphosis, reproduction, diapause and innate immunity. Ecdysteroids mediate their response by binding to a heterodimeric complex of two nuclear receptors, the ecdysone receptor (EcR) and the retinoid-X-receptor/ultraspiracle (RXR/USP). In this study we investigated the role of EcR and RXR in metamorphosis and development of the desert locust, Schistocerca gregaria. The desert locust is a voracious, phytophagous, swarming pest that can ruin crops and harvests in some of the world's poorest countries. A profound knowledge of the ecdysteroid signalling pathway can be used in the development of more target-specific insecticides to combat this harmful plague insect. Here we report an in-depth profiling study of the transcript levels of EcR and RXR, as well as its downstream response genes, in different tissues isolated throughout the last larval stage of a hemimetabolous insect, showing a clear correlation with circulating ecdysteroid titres. Using RNA interference (RNAi), the role of SgEcR/SgRXR in moulting and development was investigated. We have proven the importance of the receptor components for successful moulting of locust nymphs into the adult stage. Some SgEcR/SgRXR knockdown females were arrested in the last larval stage, and 65 % of them initiated vitellogenesis and oocyte maturation, which normally only occurs in adults. Furthermore, our results clearly indicate that at the peak of ecdysteroid synthesis, on day six of the last larval stage, knockdown of SgEcR/SgRXR is affecting the transcript levels of the Halloween genes, Spook, Shadow and Shade. PMID- 27180726 TI - Functional and immunohistochemical characterization of CCEae3a, a carboxylesterase associated with temephos resistance in the major arbovirus vectors Aedes aegypti and Ae. albopictus. AB - Temephos is a major organophosphate (OP) larvicide that has been used extensively for the control of Aedes albopictus and Aedes aegypti, the major vectors for viral diseases, such as dengue fever, zika and chikungunya. Resistance to temephos has been recently detected and associated with the upregulation of carboxylesterases (CCEs) through gene amplification, in both species. Here, we expressed the CCEae3a genes which showed the most striking up-regulation in resistant Aedes strains, using the baculovirus system. All CCEae3a variants encoded functional enzymes, with high activity and preference for p-nitrophenyl butyrate, a substrate that was shown capable to differentiate temephos resistant from susceptible Aedes larvae. Enzyme kinetic studies showed that CCEae3as from both Ae. aegypti and Ae. albopictus (CCEae3a_aeg and CCEae3a_alb, respectively) strongly interact with temephos oxon and slowly released the OP molecule, indicating a sequestration resistance mechanism. No difference was detected between resistant and susceptible CCEae3a_aeg variants (CCEae3a_aegR and CCEae3a_aegS, respectively), indicating that previously reported polymorphism is unlikely to play a role in temephos resistance. HPLC/MS showed that CCEae3as were able to metabolize temephos oxon to the temephos monoester [(4-hydroxyphenyl) sulfanyl] phenyl O,O-dimethylphosphorothioate. Western blot and immunolocalization studies, based on a specific antibody raised against the CCEae3a_alb showed that the enzyme is expressed at higher levels in resistant insects, primarily in malpighian tubules (MT) and nerve tissues. PMID- 27180727 TI - Structure, evolution, and expression of antimicrobial silk proteins, seroins in Lepidoptera. AB - The silks of silkworm and waxworm contain abundant antimicrobial proteins, including protease inhibitors and seroins. Protease inhibitors have antifungal activities, whereas seroins have antiviral and antibacterial activities. In order to obtain insights into the structure, evolution, and expression of seroins, we performed an extensive survey based on the available genome, transcriptome, and expressed sequence tags datasets. Sixty-four seroins were identified in 32 lepidopteran species. The phylogenetic and structural analyses revealed that seroins can be classified into five subfamilies: seroin 1, seroin 2, seroin 3, seroin 2 + 1, and seroin 3 + 3. It is interesting that seroin 2 + 1 contains two tandem seroin domains, seroin 2 and seroin 1, whereas seroin 3 + 3 has two tandem seroin 3 domains. Each seroin domain contains a proline-rich N-terminal motif and a conserved C-terminal motif. The transcriptome and EST data indicated that seroin 1 and seroin 2 genes were expressed in the silk gland but seroin 3 genes were not. Semi-quantitative RT-PCR and western blot analyses suggested that seroin 1 and seroin 2 were constantly accumulated in the silk gland of silkworm during the fifth instar, and then secreted into cocoon silk during spinning. Immunofluorescence analyses indicated that seroin 1 was secreted into the fibroin and sericin layers, whereas seroin 2 protein was only secreted into the sericin layer. However, the antimicrobial activity of seroin 2 was more effective than that of seroin 1. The presence of seroin 1 in the fibroin layer suggested that this protein not only acts as an antimicrobial protein, but might also play a role in the assembly and secretion of fibroins. Seroin 3, which was first identified here, might be related to pheromone synthesis or recognition, as it was highly expressed in male antennae and in the pheromone gland. PMID- 27180728 TI - High resolution study of the spatial distributions of abyssal fishes by autonomous underwater vehicle. AB - On abyssal plains, demersal fish are believed to play an important role in transferring energy across the seafloor and between the pelagic and benthic realms. However, little is known about their spatial distributions, making it difficult to quantify their ecological significance. To address this, we employed an autonomous underwater vehicle to conduct an exceptionally large photographic survey of fish distributions on the Porcupine Abyssal Plain (NE Atlantic, 4850 m water depth) encompassing two spatial scales (1-10 km(2)) on and adjacent to a small abyssal hill (240 m elevation). The spatial distributions of the total fish fauna and that of the two dominant morphotypes (Coryphaenoides sp. 1 and C. profundicolus) appeared to be random, a result contrary to common expectation but consistent with previous predictions for these fishes. We estimated total fish density on the abyssal plain to be 723 individuals km(-2) (95% CI: 601-844). This estimate is higher, and likely more precise, than prior estimates from trawl catch and baited camera techniques (152 and 188 individuals km(-2) respectively). We detected no significant difference in fish density between abyssal hill and plain, nor did we detect any evidence for the existence of fish aggregations at any spatial scale assessed. PMID- 27180729 TI - Transporter protein and drug-conjugated gold nanoparticles capable of bypassing the blood-brain barrier. AB - Drug delivery to the central nervous system (CNS) is challenging due to the inability of many drugs to cross the blood-brain barrier (BBB). Here, we show that wheat germ agglutinin horse radish peroxidase (WGA-HRP) chemically conjugated to gold nanoparticles (AuNPs) can be transported to the spinal cord and brainstem following intramuscular injection into the diaphragm of rats. We synthesized and determined the size and chemical composition of a three-part nanoconjugate consisting of WGA-HRP, AuNPs, and drugs for the treatment of diaphragm paralysis associated with high cervical spinal cord injury (SCI). Upon injection into the diaphragm muscle of rats, we show that the nanoconjugate is capable of delivering the drug at a much lower dose than the unconjugated drug injected systemically to effectively induce respiratory recovery in rats following SCI. This study not only demonstrates a promising strategy to deliver drugs to the CNS bypassing the BBB but also contributes a potential nanotherapy for the treatment of respiratory muscle paralysis resulted from cervical SCI. PMID- 27180730 TI - Accuracy of Estimating Step Counts and Intensity Using Accelerometers in Older People With or Without Assistive Devices. AB - The purpose of this study was to examine the accuracy of uni- and triaxial accelerometers in monitoring step counts and gait intensity in older people who did or did not use an assistive device. Forty-nine healthy and frail older adults wore uniaxial (Lifecorder, Suzuken Co. Ltd.) and triaxial accelerometers (Activity Monitor, Matsushita Electronic Works, Ltd., and Active Style Pro, Omron Healthcare Co., Ltd.) during three trials at different gait speeds. All accelerometers gave relatively accurate step counts for healthy older participants compared with direct observation; however, the error was greater for frail older people with assistive devices. Gait intensity detection error was unaffected by gait speed. Among frail older people with assistive devices, the gait intensity error was smaller than for step count error. To accurately assess the steps walked or the gait intensity among frail older people using assistive devices, more study is needed on these groups of participants. PMID- 27180731 TI - Syphilis iridocyclitis in a patient with type 1 diabetes. AB - We present a rare cause of iridocyclitis in a patient with vitiligo and type 1 diabetes who showed poor metabolic control, and suffered from remitting fever, weight loss, fatigue, diffuse arthralgias and reduced visual acuity. Mild systemic symptoms coupled with increased cholestasis enzymes, insulin resistance, mild inflammation and a functioning adrenal gland focused our clinical work-up on granulomatous causes of iridocyclitis. Specific tests confirmed syphilis, with no involvement of the central nervous system. Ocular syphilis, despite being unusual, can be the only manifestation of the disease. The work-up of any unexplained ocular inflammation should include testing for syphilis so as to not delay the diagnosis. PMID- 27180732 TI - DNA barcoding of three species (Canis aureus, Canis lupus and Vulpes vulpes) of Canidae. AB - Sequences of the mitochondrial cytochrome c oxidase subunit I (COI) gene have been used for DNA barcoding and determining the genetic diversity of mammal species. In the current study, our intention was to test the validity of COI barcodes for detecting genetic divergence and to reveal whether or not there is a genetic variation at this marker within canids. Three species (Canis aureus, Canis lupus and Vulpes vulpes) from the family Canidae were selected for DNA barcoding using samples collected from Iran and Turkey. All three species had unique barcoding sequences and none of the sequences were shared among these species. The mean sequence divergences within and among the species were 0.61% and 12.32%, respectively, which fell into the mean divergence ranges found in some mammal groups. The genetic diversity of these three canid species was relatively higher than that found in previously reported studies. PMID- 27180734 TI - Acetylation of aromatic cysteine conjugates by recombinant human N acetyltransferase 8. AB - 1. The mercapturic acid (MA) pathway is a metabolic route for the processing of glutathione conjugates to MA (N-acetylcysteine conjugates). An N acetyltransferase enzyme, NAT8, catalyzes the transfer of an acetyl group from acetyl-CoA to the cysteine amino group, producing a MA, which is excreted in the urine. We expressed human NAT8 in HEK293T cells and developed an HPLC-MS method for the quantitation of the S-aryl-substituted cysteine conjugates and their MA. 2. We measured the activity of the enzyme for acetylation of benzyl-, 4 nitrobenzyl-, and 1-menaphthylcysteine substrates. 3. NAT8 catalyzed the acetylation of all three cysteine conjugates with similar Michaelis-Menten kinetics. PMID- 27180733 TI - Challenging Case of Postmenopausal Bleeding and Complete Urogenital Duplication. AB - BACKGROUND: Mullerian duct anomalies represent a wide spectrum of congenital abnormalities ranging from simple uterine anomalies to more complex multisystem derangements. Complete duplication of uterus, cervix, and vagina may be associated with urologic and caudal gastrointestinal malformations. CASE REPORT: We present a case report detailing the management of a morbidly obese patient with postmenopausal bleeding and thickened endometrial stripe who had a very rare condition of pelvic organ duplication, including 2 hemiuteri, 2 vaginas, 2 hemibladders, and 2 each of ovaries, fallopian tubes, kidneys, and ureters. Laparoscopic hysterectomy was complicated by difficulties understanding urinary system anatomy requiring intraoperative urology consultation and imaging. CONCLUSIONS: Management of patients with urogenital duplication and abnormal uterine bleeding requires a thorough understanding of possible associated malformations. Thorough preoperative evaluation, careful surgical exploration, and multidisciplinary approach may be necessary to avoid urologic injury in such patients. PMID- 27180735 TI - Closing the knowledge gaps on MERS: three and half years since its detection, what have we learnt and what needs to be done urgently? PMID- 27180736 TI - Evaluation of factors associated with failure of tuberculosis treatment under DOTS in northern Islamic Republic of Iran. AB - Tuberculosis treatment failure remains a major health problem in many parts of the Islamic Republic of Iran. This study was conducted to identify the risk factors associated with failure of tuberculosis treatment under the DOTS strategy in two cities of Golestan province. A retrospective cohort study in 2012-2013 was conducted on 167 smearpositive tuberculosis patients monitored under DOTS. Demographic, clinical and treatment outcome factors and social determinants of health were recorded for each patient. Multivariate regression analysis found that the strongest predictors of tuberculosis treatment failure were: being infected with other diseases (OR 9.35; 95% CI: 3.01-29.1), male sex (OR 5.03; 95% CI: 1.58-16.1), Turkoman ethnicity (OR 11.0; 95% CI: 2.00-60.1), family history of tuberculosis (OR 0.21; 95% CI: 0.05-0.96) and household size (OR 1.21; 95% CI: 0.99-1.48). Recommendations include better follow-up for patients with other diseases and facilitating access to treatment, especially for Turkoman patients. PMID- 27180737 TI - Epidemiology of tuberculosis and evaluation of treatment outcomes in the national tuberculosis control programme, River Nile state, Sudan, 2011-2013. AB - Tuberculosis is a major health problem in Sudan, a country that carries 11-15% of the tuberculosis burden in the Eastern Mediterranean Region. This study aimed to describe the epidemiology of tuberculosis in River Nile State and to compare treatment outcomes with WHO recommended indicators. A descriptive study was conducted on data collected from records of 1221 patients registered at tuberculosis management units over the 3 years 2011-2013. The mean age of cases was 37.7 (SD 21.5) years and 65.9% were males; 76.3% were pulmonary tuberculosis and 36.9% were sputum smear-positive cases. Average values for all outcome indicators were suboptimal, notably rates of case notification (30.8 per 100 000), case detection (10.3%), treatment success (79.6%), treatment failure (3.0%), default (8.1%) and death (8.0%). Of the 264 patients tested for HIV, 3.8% were positive. Outcome indicators for the national tuberculosis control programme are lagging behind the required targets. PMID- 27180738 TI - Descriptive epidemiology of physical activity among Omani adults: the Oman World Health Survey, 2008. AB - There is an increasing burden of obesity and obesity-related noncommunicable diseases in Gulf Cooperation Council countries, including Oman. This descriptive, epidemiological study assessed physical activity among 2977 Omani adults using a population-based household survey in 2008. Overall, 54.2% of men and 41.6% of women were physically active; the rate was higher in younger cohorts and varied significantly by region of residence. Physical activity related to the transportation (walking and cycling) domain was higher than in the leisure or work domains. Unmarried men aged 30-39 years were twice as likely to be physically active (OR 2.25) and unmarried women aged 40+ years were half as likely to be active (OR 0.58) than their married counterparts. Young women not working were less active (OR 0.18) than working women. Higher education was significantly associated with leisure activity for men aged 30+ years and women aged 40+ years. Further research to understand regional variations and to identify culturally appropriate strategies to promote physical activity is required. PMID- 27180739 TI - Exploring the characteristics of public reproductive health services in the Islamic Republic of Iran from the perspectives of unmarried women: what needs to be changed? AB - This qualitative study in the Islamic Republic of Iran aimed to explore facilitators and barriers to the use of reproductive health services by unmarried women. A purposive sample of unmarried women aged 25-60 years in Isfahan city were interviewed about their experiences of reproductive health services in public health centres. Content analysis of responses revealed that the favourable characteristics of reproductive health services in public centres were services that: were delivered by personnel of the same sex in a woman-friendly environment and available at a suitable price, and did not label clients. In contrast, the following characteristics made public health centres undesirable for unmarried women: not addressing single women for reproductive health services; lack of privacy; failure to maintain confidentiality; doubts about skills and scientific ability of personnel; and lack of integration of services. PMID- 27180740 TI - Men's perceptions of and participation in family planning in Aqaba and Ma'an governorates, Jordan. AB - Men's participation in family planning has become a cornerstone in women's reproductive health. The aim of this study was to examine knowledge, attitudes and practice towards family planning of Jordanian men in southern Jordan. In a cross-sectional descriptive study in 2012, structured interviews were made with 104 married men in Aqaba and Ma'an governorates. Although 93.5% of the men had heard about family planning-most commonly the intrauterine device (IUD) and oral contraceptives-only 45.1% reported that they and their wife currently used it. Most men agreed about a minimum 2 years' child spacing (93.3%) and starting contraception after childbirth (71.2%) and that husband and wife should share decisions about family planning (90.2%) and the number of children (89.5%). Level of education significantly affected current use of contraception, while number of children significantly affected previous use of contraception. Although married men had positive attitudes and good knowledge about family planning, this did not translate into practice of contraceptive use. PMID- 27180741 TI - Measuring health-related quality of life in the population of Tetouan, Morocco, by the SF-36: normative data and the influence of gender and age. AB - Measuring health-related quality of life (HRQOL) is an essential complement to medical evaluation. However, few studies of this type have been conducted in Morocco. This study aims to develop normative data for the SF-36 and analyse the HRQOL according to gender and age in the population of Tetouan city, Morocco. The SF-36 was administered to a sample selected by quotas containing 385 subjects aged over 16 years living in Tetouan. Comparisons of means were done to determine the significance of differences. The study population perceived mental health to be worse than physical health. Men presented significantly higher mean scores than women for all domains of the SF-36. Perceived health, especially physical health, declines with age, and so participants over the age of 55years recorded a poor perception of their health in the majority of domains measured. The results highlight the vulnerability of the two groups: women and the elderly. PMID- 27180742 TI - Isolation frequency and susceptibility pattern of non-O1 and non-O139 Vibrio cholerae in a tertiary health care laboratory, 1999-2012. AB - In the past decade the importance of non-O1 and non-O139 strains of Vibrio cholerae has been highlighted globally. This study aimed to evaluate the frequency and antimicrobial susceptibility profile of non-O1 and non-O139 V. cholerae in Pakistan. Data of stool specimens yielding growth of non-O1 and non O139 V. cholerae isolated at a national referral laboratory from 1999 to 2012 were retrospectively analysed and evaluated for resistance to ampicillin, tetracycline, chloramphenicol, co-trimoxazole and ofloxacin. A total of 95 800 stool samples submitted over 1999-2012 yielded 3668 strains of V. cholerae, of which 6% were non-O1 and non-O139 V. cholerae. A high isolation rate was found in the summer season, with a peak in the year 2003. Antimicrobial susceptibility data revealed increasing resistance to co-trimoxazole and ampicillin, but strains remained highly susceptible to ofloxacin. Active surveillance of serotypes and antimicrobial susceptibility is essential to predict future epidemics and define measures to curtail the disease. PMID- 27180744 TI - [Focus on the mechanisms of diabetic kidney disease]. PMID- 27180743 TI - Evaluating the English language scientific writing skills of Saudi dental students at entry level. AB - Better knowledge is needed about the effectiveness of preparatory English language courses for the health professions. This study evaluated the scientific writing skills of students finishing their preparatory year of a bachelor of dentistry programme in Saudi Arabia. A cross-sectional study was conducted in 2014-15 among first-year dental students at the University of Dammam. Students were asked to write a 150-word English language assignment that was analysed for writing statistics and problems using Microsoft Word and plagiarism detection software. Of the 89 respondents, female students used a significantly greater number of words than did male students and their assignments had significantly lower Flesch reading ease scores. Male students had significantly lower odds of using references (OR 0.04) and higher odds of making punctuation and grammar mistakes (OR 2.63 and 3.91 respectively). One course of scientific writing in the preparatory year may not be enough to develop adequate writing skills among undergraduate dental students. PMID- 27180745 TI - [Genetics of diabetic nephropathy]. PMID- 27180746 TI - [Value of estimated glomerular filtration rate in diagnosis of senile diabetic kidney disease]. PMID- 27180747 TI - [Correlation between serum free fatty acid level and estimated glomerular filtration rate in type 2 diabetic patients]. AB - OBJECTIVE: To investigate the relationship between serum free fatty acid (FFA) level and glomerular filtration rate (GFR) in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 442 T2DM patients treated in Sir Run Run Shaw Hospital from January 2013 to June 2015 were retrospectively analyzed and divided into three groups according to estimated glomerular filtration rate (eGFR) levels using modified modification of diet in renal disease (MDRD) formula: eGFR>=90 ml.min(-1).1.73 m(-2)group (group A, 227 cases), 60 ml.min( 1).1.73 m(-2)<=eGFR<90 ml.min(-1).1.73 m(-2)group (group B, 118 cases), and eGFR<60 ml.min(-1).1.73 m(-2)group (group C, 97 cases). In addition, 50 body mass index (BMI)-matched non-diabetic subjects were selected as control group. Fasting serum FFA level was measured in each group, and its relationship with eGFR was analyzed. RESULTS: FFA level in group C[(450+/-203)MUmol/L]was significantly higher than that in group A[(326+/-167)MUmol/L], group B[(394+/-184)MUmol/L]and control group[(320+/-90)MUmol/L](all P<0.05). Meanwhile, FFA level in group B was higher compared with that in group A (P<0.05). However, no statistical difference was found in FFA level between group A and Control group (P>0.05). Multiple linear regression analysis using eGFR as the dependent variable demonstrated that uric acid (UA), FFA, triglyceride (TG), total cholesterol (TC), albuminuria, hypertension, smoking and duration of diabetes were all independent risk factors for decreased eGFR (all P<0.05). CONCLUSION: The present results suggest that increased FFA level might be involved in the development of diabetic nephropathy. PMID- 27180748 TI - [Effect of metanephric mesenchyme cells on podocytes apoptosis induced by high glucose]. AB - OBJECTIVE: To study the effect of metanephric mesenchyme cells on podocytes apoptosis induced by high glucose. METHODS: Mice's podocyte was cultured in vitro,and apoptosis and injury model of podocyte was then established by high glucose (30 mmol/L) induction. Metanephric mesenchyme cells were extracted from E13.5 mouse embryos and used to make conditioned medium which was used to treat podocytes apoptosis. The flow cytometry and confocal fluorescence imaging were used to detect the apoptosis ratio and cytoskeletal protein (synaptopodin) expression of podocyte at several time points (24, 48, 72 h), in order to explore the effect of high glucose on podocytes and the treatment effect of metanephric mesenchyme cell conditioned medium. RESULTS: Significant increasing of podocyte apoptosis ratio and decreasing in synaptopodin expression contrast to control group was observed after induction of high glucose, with a statistical difference. Metanephric mesenchyme cells could be isolated from E13.5 mouse embryos successfully, and had the capacity of osteogenic and adipogenic differentiation. Metanephric mesenchyme cell conditioned medium and high glucose stimulations was used to generate podocytes cells. Compared to the group treated with high glucose stimulation, the flow cytometry detection result suggested that metanephric mesenchyme cell could reduce podocytes apoptosis in a dose-dependent manner: with increasing in the concentration of metanephric mesenchyme cell conditioned medium, the treatment effect was better. CONCLUSION: Metanephric mesenchyme cells could prevent apoptosis and injury of podocyte induced by high glucose. PMID- 27180749 TI - [In vivo study of the renoprotective effects of EGCG in diabetic db/db mice]. AB - OBJECTIVE: To explore the renoprotective effects of (-)-epigallocatechin-3 gallate (EGCG) and its potential mechanism in type 2 diabetic db/db mice. METHODS: 8-week-old db/db mice (6 h fasting plasma glucose >16.7 mmol/L) were allocated randomly into Control group (non-intervention group, n=8), EGCG A group (50 mg.kg(-1).d(-1,)n=8), EGCG B group (100 mg.kg(-1).d(-1,)n=8). Before the study and after the intervention (in the 4(th)and 8(th)week), the body weight, the level of fasting plasma glucose, oral glucose tolerance test (OGTT) were measured and 24 h urine samples were collected. 24 h proteinuria was measured by routine chemical method. The levels of angiotensin II(AngII), fasting plasma insulin and urinary 8-OHdG were measured with enzyme-linked immunosorbent assay (ELISA). The protein expression levels of angiotensin II type 1 receptor (AT-1R), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit P22-phox, NADPH oxidase subunit P47-phox, phospho-extracellular regulated protein kinases (p-Erk1/2), phospho-P38 mitogen-activated protein kinase (p-P38MAPK), phospho phosphatidylinositol 3-hydroxy kinase (p-PI3K) and phospho-protein kinase B (p AKT) were determined by Western blot. The renal pathological changes were examined by the method of PAS (periodic acid-Schiff stain). RESULTS: After 8 weeks of treatment with EGCG, the level of fasting plasma glucose decreased[(14.4+/-1.0) mmol/L, (14.2+/-0.7) mmol/L vs. (17.2+/-0.8) mmol/L]; the level of fasting plasma insulin increased[(13.2+/-1.2)mU/L, (13.4+/-1.3) mU/L vs. (9.9+/-1.0) mU/L]; the area under the curve (AUC) of OGTT decreased[(49.3+/-1.8) mmol.L(-1).h(-1,)(44.8+/-0.7) mmol.L(-1).h(-1)vs. (60.0+/-0.8) mmol.L(-1).h(-1)]; the level of 24 h proteinuria[(8.8+/-1.0) mg, (8.6+/-1.1) mg vs. (11.7+/-1.3) mg]and urinary 8-OHdG[(90+/-5) ng/d, (78+/-5) ng/d vs. (118+/-10) ng/d]decreased; the level of serum Ang-II[(498+/-23) ng/L, (511+/-19) ng/L vs. (688+/-17) ng/L]and renal cortex AngII[(367+/-5) ng/L, (384+/-10) ng/L vs. (406+/-7) ng/L]decreased; the expression levels of AT-1R, P22-phox, P47-phox, p-Erk1/2, p P38MAPK downregulated obviously and the expression levels of p-PI3K, p-AKT increased significantly (P<0.05), and renal pathology improved as compared with the control group. After 8 weeks of treatment with EGCG, the level of urinary 8 OHdG decreased (P=0.007) and the AUC of OGTT also decreased (P=0.01) in EGCG B group when compared with the EGCG A group. CONCLUSION: EGCG protects the kidney in diabetic db/db mice via anti-oxidative stress pathway, as well as inhibiting Erk1/2-P38MAPK pathway and improving PI3K-AKT signaling transduction pathway. PMID- 27180750 TI - [Clinical characteristics of acute cerebral hemorrhage in patients with systemic malignancy]. AB - OBJECTIVE: To investigate the clinical features of systemic malignancy patients with acute cerebral hemorrhage as well as its underlying mechanism. METHODS: The clinical data, including presentation, lab tests and neurological images, of systemic malignancy patients with acute cerebral hemorrhage at the First Affiliated Hospital of Guangxi Medical University between January 2003 and December 2014 were collected and analyzed. RESULTS: Among 61 326 systemic malignancy patients, 25 patients(0.04%)were found with acute cerebral hemorrhage and were enrolled. Out of these 25 patients, age ranged from 31 to 77 years old, with an average age of 61 years, 18 patients were males. The clinical features of the systemic malignancy patients with acute cerebral hemorrhage were found that most patients (14/25, 54.0%) lacked traditional risk factors, with sudden symptom onset and some degree of neurologic deficiency in all patients, and most hemorrhagic lesions (19/25, 76.0%) involved the hemicerebrum, for most patients (16/25, 60.0%) cerebral hemorrhage occurred after 3 days to 3 years of the malignancy diagnosis, and some malignancy patients (8/25, 32.0%) presented with cerebral hemorrhage as the first presentation. The common subtypes of malignancy found were lung cancer (8/25, 32.0%), liver cancer (7/25, 28.0%), and then gastric carcinoma (6/25, 24.0%). Most patients (22/25, 88.0%) had elevated plasma level of cancer biochemical marks (including one or more than one of cancer antigen 125, 153 and 199, carcino-embryonic antigen, and alpha fetal protein), most patients (16/25, 64.0%) were found to have coagulation disorder. CONCLUSIONS: The unique clinical features of the systemic malignancy patients with acute cerebral hemorrhage are most patients lacking traditional risk factors, with coagulation disorder and with hemorrhagic lesions in hemicerebrum. And coagulation disorder might be responsible for the cerebral hemorrhage. PMID- 27180751 TI - [Safety of implantation permanent pacemaker at different times in patients with dual antiplatelet therapy]. AB - OBJECTIVE: To investigate the safety of implantation permanent pacemaker (PM) at different times in patients with dual antiplatelet (DAPT) therapy after implantation of drug-eluting stent (DES). METHODS: A total of 105 patients who implanted pacemakers with DAPT therapy (clopidogrel and aspirin) after implantation of DES admitted to our hospital from January 2009 to January 2015 were enrolled in the study. The patients were divided into 3 groups: dual antiplatelet therapy (DAP) group: implanting PM within 3 months after coronary stenting, continuous DAPT during perioperative period; low molecular weight heparin (LMWH) bridging group: implanting PM within 3 to 6 months after coronary stenting, DAPT interruption for 5 days replaced with subcutaneous injection of enoxaparin (1 mg/kg), twice per day, enoxaparin was stopped 12 h before operation; asprin group, implanting PM after coronary stenting 6 months, clopidogrel interruption for 5 days. Oral DAPT was returned 12-24 after operation according to the patients' condition. Peri-operative cardiovascular events and bleedings, infections were observed. RESULTS: There was no major adverse cardiac event (MACE) and pouch infection were observed among 3 groups in perioperation. The incidence of pocket hemorrhage and errhysis in bridging group was significantly higher than that of DAP group and asprin group (16.7%, 8.0%, 0.0% chi(2)=10.431, P=0.005 and 29.2%, 12.0%, 7.1% chi(2)=6.321, P=0.042 respectively). 3 patients had severe bleeding (12.5%, 3/24) in bridging group; compared with the other 2 groups, there were significant difference (chi(2)=9.161, P=0.010). The incidence of hematoma and hemorrhage of asprin group was lowest. CONCLUSIONS: LMWH bridging therapy significantly increases the risk of pacemaker pocket hematoma and hemorrhage, and the pacemaker implantation may be safer after DES implantation 6 months. PMID- 27180752 TI - [Effect of preoperative factors on the clinical outcome of total knee arthroplasty]. AB - OBJECTIVE: To analyze the effect of preoperative factors on the clinical outcome in patients receiving total knee replacement. METHODS: From January 2011 to September 2013, 145 patients (206 knees; 22 males, 31 knees; 123 females, 175 knees)receiving total knee arthroplasty were successfully included in this study and followed up. The average ages was (66.5+/-7.6) years old(range, 51-83 years old). The data of preoperative factorsincludedgender, age, body mass index (BMI), preoperative range of motion (ROM), the knee varus angle, flexion deformity and preoperative the hospital for special surgery (HSS) scorewere collected. The correlation between preoperative factors and the clinical outcome (postoperative HSS score, postoperative ROM)after total knee replacement was evaluated statistically. RESULTS: The average follow-up time was 35 months (range, 24-56 months). The HSS score was increased from (55.1+/-7.6) preoperativelyto (89.3+/ 5.1) postoperatively. ROM elevated from (95.6+/-10.0) degrees preoperatively to (115.1+/-7.8) degrees postoperatively.The correlation analysis showed that the postoperative ROM was positively correlated with the preoperative ROM, and was negatively correlated with the BMI, the knee varus angle(r=-0.864, -0.353, all P<0.01). The postoperative HSS score was positively correlated with preoperative ROM, preoperative HSS score(r=0.101, 0.244, P=0.033, P<0.01), and was negatively correlated with the BMI (r=-0.277, P=0.039). CONCLUSIONS: Total knee arthroplasty can definitely improve the function of knee joint. The BMI, the preoperative ROM, the knee varus angle and preoperative HSS score have influence on postoperative function of patients receiving total knee arthroplasty. PMID- 27180753 TI - [Diagnosis and management of atypical femoral fractures: clinical efficacy in 11 cases]. AB - OBJECTIVE: To evaluate the clinical efficacy of intramedullary nail fixation in atypical femoral fractures and explore the management approach. METHOD: From January 2010 to December 2014, a total of 116 patients over 60 years old with femoral intertrochanteric fractures or femoral shaft fractures were treated in Department of Orthopaedics and Traumatology. Among the patients, 11 with atypical femoral fractures, aged from 62 to 82 ( 69.3+/-5.6) years old, received surgical treatments. There were 2 males (18.2%) and 9 females (81.8%). 5 patients (45.5%) had the prodromal symptom of thigh pain. 9 patients (81.8%) had the history of long-term use of bisphosphonates with the duration of 3 to 9 (5.3+/-2.1) years. All the fractures received close reduction and antegrade intramedullary nail fixation. The Thoresen score and EuroQol 5 dimensions scores (EQ-5D) were applied to evaluate the extremity function and life quality after surgery. RESULT: All the operations were performed successfully. At least 1 years follow-up was accomplished with the follow-up period of 1 to 4 (1.8+/-0.9) years. There were 8 (72.7%) excellent, 2 (18.2%) good, 1 (9.1%) fair according to the Thoresen score with total excellent to good rate up to 90.9% at the last follow-up. The EQ-5D scores showed the life quality was similar with that before injury (P>0.05). Fracture healing was achieved in all 11 cases with time from 3 to 8 (5.7+/-1.6) month. There was no case complicated with infection, nonunion or implant failure during the follow-up period. No contralateral atypical femoral fracture was observed. CONCLUSION: Atypical femoral fractures are uncommon in the clinical practice. Accurate diagnosis and appropriate management approach are the keys of satisfactory outcomes. PMID- 27180754 TI - [Establishment of a predicting model to evaluate the probability of malignancy or benign in patients with solid solitary pulmonary nodules]. AB - OBJECTIVE: To develop a predicting model for evaluating the probability of malignancy or benign in patients with solid solitary pulmonary nodules through analyzing the clinical, radiologic, laboratory examination and radionuclide (18)F Fluorodeoxyglucose examinations data. METHODS: The data of the 203 patients(110 males and 93 females) with solid SPN who underwent surgical resection with definite postoperative pathological diagnosis from January 2012 to December 2014 in Shanghai Chest Hospital (group A)were retrospectively analyzed. The clinical data included age, gender, history of smoking, history of tumor; radiologic data included diameter in lung window, location, shape, clear border, lobulation, spiculation, vascular convergence, tumor cycle blood vessel, density, calcification, pleura indentation; laboratory examination included five serum tumor markers consisting of CA125, CEA, CYFRAL21-1, NSE, SCC. (18)F Fluorodeoxyglucose examinations included (18)F-FDG PET-CT or SPECT. The independent predictors of malignancy were estimated through univariate and multivariate analysis, then the predicting model was built. Another 110 patients with solid SPN(group B)from January 2015 to December 2015 with definite pathological diagnosis were used to validate the predictive value of the model. RESULTS: There were 159(78.3%) cases of malignancy and 44(21.7%) cases of benign in group A. Logistic regression analysis showed age, clear border, spiculation, calcification and (18)F-FDG examination were independent predictors of malignancy in patients with solid SPN(P<0.05). A predicting nomogram was built according to the result of the multivariate logistic regression analysis. The area under the ROC curve was 0.890+/-0.038 for group B. The cut off value was 0.708. The sensitivity in group B was 86%, specificity 80%, accuracy 84.5%. CONCLUSION: Age of patients, clear border, spiculation, calcification and (18)F-FDG examination were independent predictors of malignancy in patients with solid SPN. The model showed good diagnosis efficiency in external validation, and could be applied to make decision for patients with solid SPN. PMID- 27180755 TI - [Clinical value of lung ultrasound in the late goal-directed fluid removal in critically ill patients underwent fluid resuscitation]. AB - OBJECTIVE: To investigate the clinical value of lung ultrasound in the late goal directed fluid removal in critically ill patients underwent fluid resuscitation. METHODS: A prospective study was conducted. Forty patients underwent fluid resuscitation were enrolled in the Department of Surgical Intensive Care Unit of The First Affiliated Hospital of Sun Yat-sen University from Jan 2015 to June 2015. Lung and heart ultrasound were conducted for lung B-lines and left ventricular ejection fraction (EF). Serum amino-terminal pro-brain natriuretic peptide (NT-proBNP), central venous pressure (CVP) and serum creatinine were also measured and fluid balance was recorded in all patients enrolled. RESULTS: Among the 40 patients enrolled, 35 patients survived and 5 died. In patients survived, B-lines reached its peak at 12(30)h after admitted to ICU. It started to decrease instantly after the peak and reached zero at (39+/-34) h. A higher peak was followed with more fluids to be removed later and longer ICU stay (P<0.01). Moreover, when compared with the survivors, B-lines in death reached a higher peak[7(8) vs 3(4), P<0.01]and without the tendency to drop down. EF was lower in death than in survivor (44.5%+/-3.5% vs 69.2%+/-11.0%, P<0.05). A lower EF was found to be followed with a higher peak of B-lines. The peak time of NT-proBNP and clinical dehydration treatment were later than the peak time of B-lines in survivors. CONCLUSIONS: Fluid overloading occurs in late stage after resuscitation in critically ill patients. Lung ultrasound B-lines, which is more sensitive than the NT-proBNP and CVP, could help to monitor the patient's fluid status and guide the late goal-directed fluid removal. PMID- 27180756 TI - [Hodotopical researchonneural pathway of Chinese language in posterior inferior frontal gyrus]. AB - OBJECTIVE: To investigate the hodotopical organization of neural pathway of Chinese in posterior inferior frontal gyrus. Forprovide the basis for the individual protectionoflanguage functionin the operation of the language functional area. METHODS: Twenty volunteers underwentlanguage mapping using repetitive navigated transcranial magnetic stimulation(nTMS)to identify the essential language sites in posterior inferior frontal gyrus.Then, DTI tractography was used to reconstruct language-relevant fiber tracts within posterior inferior frontal lobe. Finally, the relationships between essential language sites and language-relevant fiber tracts were analyzed. RESULTS: (1)Eighteen subjects hadlanguage sites which induce repeatable language errors in posterior inferior frontal gyrus. The total number of essential language sites was 39.46% of essential language sites located in ventral precentralgyrus, 41% in parsopercularis and 13% in parstriangularis. (2)Long segment of arcuate fasciculus had the probability of 100%to project into ventral precentralgyrus. Anterior segment of arcuate fasciculus had the probability of 100%to project into ventral precentralgyrus. Inferior frontal occipital fasciculus had the probability of 94% to project into parstriangularis. Uncinate fasciculus had the probability of 67% to project into parstriangularis. Aslantfiber had the probability of 100% to project into parsopercularis.(3)When the essential language site located in ventral precentralgyrus, it had the probability of 82% to correlate with long segment of arcuate fasciculus. When the essential language site located in parsopercularis, it had the probability of 79%to correlate with aslant fiber. When the essential language site located in parstriangularis, it had the probability of 60% to correlate with inferior frontal occipital fasciculus. CONCLUSION: Essential language sites within distinct locations were conducted through different fasciculus, which enlightensour neurosurgeons thatin order to achieve both maximal lesions resection and language function protection, we shouldprotectboththe essential language cortices and language relevant subcortical connection according to each individual's hodotopical organization. PMID- 27180757 TI - [The clinical characteristics and microsurgery treatment of patients with spinal cord glioblastoma]. AB - OBJECTIVE: The aim is to explore the clinical characteristics of spinal cord glioblastoma and the therapeutic effect of microsurgery. METHODS: The clinical data of 18 patients with spinal cord glioblastoma from January 2011 to December 2014 in Beijing Tiantan Hospital were retrospectively analyzed including the clinical characteristics, the microsurgery treatment and the postoperative radiochemotherapy. RESULTS: There were 12 cases for subtotal resection, 4 cases for partial resection and 2 cases for biopsy of the intraspinal tumors under microscope. The nervous system symptoms were improved in 11 cases, no changes in 5, deterioration in 2 and no deaths within 3 months after the operation. Among those, 5 cases (100%) with preoperative McCormick grade I, 4 (57%) with grade II, 2 (50%) with grade III, and 0 with grade IV had improved. There were McCormick gradeI8 cases, grade II 5 cases, grade III 2 cases and grade IV 3 cases within 3 months after the operation. Seventeen patients were followed up from 6 to 36 months, and 1 patients was lost to follow-up. Five patients returned to normal work and study, while 8 died. The median survival time was 16 months. CONCLUSIONS: Spinal cord glioblastoma is highly malignant with low incidence and poor prognosis, which should be performed by early operative treatment and postoperative adjuvant radiochemotherapy. PMID- 27180758 TI - [Value of susceptibility weighted imaging in hepatic fibrosis staging by using MR in a rabbit model]. AB - OBJECTIVE: To assess the feasibility of susceptibility weighted imaging (SWI) in staging hepatic fibrosis(HF). METHODS: Sixty healthy rabbits were divided into three groups: HF group(n=32), control group(n=16), supplementary group(n=12). Rabbits in HF group and supplementary group were injected subcutaneously with 50% CCl4 oil solution to establish hepatic fibrosis model. On the basis of preliminary test, eight rabbits from HF group and four rabbits from control group underwent liver conventional MR scans and SWI once a time at 4, 5, 6, 10 weeks after CCl4 administration.After MR scans at each time point, rabbits were killed to detect pathological staging with Scheuer staging.The liver signal intensity (SI) and liver-to-muscle SI ratios (SIR) were measured. According to the Scheuer classification of histological fibrosis stages, the correlation about the SI value, SIR value and the histological fibrosis stages was investigated by using the Spearman correlation test. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of SWI for staging HF on the basis of the histopathologic analysis of HF. RESULTS: There were fifteen rabbits in pathological staging F0, the value of SIR and SI was 0.974 +/- 0.018, 374+/ 44, SIR values of pathological staging from F1 to F4 were 0.963 +/- 0.018, 0.796 +/- 0.023, 0.786 +/- 0.025, 0.512+/-0.024 respectively. SI values of pathological staging from F1 to F4 were 372+/-18, 376+/-22, 346+/-15, 288+/-19 respectively. In the early period of liver fibrosis, there were no statistical differences in the SI value between F0 and F1, F1 and F2 stage.With progression of hepatic fibrosis, from F2 to F4, SI value decreased, the difference was statistically significant (P<0.05). With the progress of liver fibrosis, SIR value was reduced. It was negatively correlated with the HF stages and SIR value(r=-0.896, P<0.05). ROC curve analysis showed that the efficiency of SI value diagnosis in liver fibrosis was high in the late stage of liver fibrosis, but it was low in the early stage.The performance of liver-to-muscle SI ratio on SWI was high in the early stage. Liver-to-muscle SI ratio had a higher diagnostic performance than SI in the diagnosis of liver fibrosis stages. CONCLUSION: SWI can be a safe, reliable method for staging hepatic fibrosis and provide quantitative imaging basis for clinical treatment. PMID- 27180760 TI - [Effects of subchorionic hematoma on pregnancy outcome: a meta analysis]. AB - OBJECTIVE: To study the effects of subchorionic hematoma (SCH) on pregnancy outcome. METHODS: We searched publications from January 2000 to July 2015 for cohort and case-control studies evaluating subchorionic hematoma and perinatal outcomes, including spontaneous abortion, premature delivery and delivery mode. RESULTS: Data of 6 articles analyzed by meta-analysis showed that SCH group had higher rate of spontaneous abortion, while no difference in premature delivery and delivery mode, compared with threatened abortion group. CONCLUSION: Subchorionic hematoma increases the risk of spontaneous abortion, while premature delivery rate and delivery mode are not affected if the pregnant women can continue the pregnancy. PMID- 27180759 TI - [Meta-analysis of the combination of warfarin and clopidogrel after coronary stenting in patients with indications for chronic oral anticoagulation]. AB - OBJECTIVE: To investigate the safety and efficacy of dual antithrombotic regimen of warfarin and clopidogrel in patients who underwent coronary stenting and were with chronic oral anticoagulation. METHODS: Two investigators independently searched Pubmed, Embase and Cochrane for all reported studies, and yielding 6 articles, published before April 2015, enrolling 4 825 patients, follow-up for at least 12 months. Two investigators independently recorded the data regarding interventions and the occurrence of major bleeding, ischemic stroke, myocardial infarction and death. RevMan5.3 was used to do analysis. RESULTS: Patients on dual antithrombotic regimen had insignificant reduction in major bleeding (odds ratio[OR]was 0.73, 95% confidence interval[CI]was from 0.46 to 1.14, and P=0.16) as compared with triple therapy. While the risk of ischemic stroke (OR= 0.78, 95%CI:0.44-1.38, P=0.39), myocardial infarction (OR= 1.19, 95%CI:0.92-1.53, P=0.18) and the overall incidence of death (OR=0.95, 95%CI:0.56-1.60, P=0.84) were also comparable between the two regimens. CONCLUSION: Dual antithrombotic regimen of warfarin and clopidogrel is comparable to the recommended triple therapy in respect to the prevention of thromboembolic outcomes of MI/ death and ischemic stroke, while the risk of bleeding is similar in those patients with indications for chronic oral anticoagulation undergoing percutaneous coronary intervention with stent implantation. PMID- 27180761 TI - Corrigendum. PMID- 27180784 TI - In vivo antibacterial activity of Garcinia mangostana pericarp extract against methicillin-resistant Staphylococcus aureus in a mouse superficial skin infection model. AB - CONTEXT: Garcinia mangostana Linn. (Guttiferae) (GM) pericarp has been shown to exhibit good in vitro antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA); however, there is currently no available information regarding its in vivo antibacterial activity. OBJECTIVE: To examine in vivo antibacterial activity of G. mangostana extract against MRSA. MATERIALS AND METHODS: GM pericarp was extracted by ethanol (GM-EtOH) and methanol (GM MeOH). The crude extracts were examined for in vitro antibacterial activity against MRSA using broth microdilution assay. The in vivo antibacterial activity of 10% GM-EtOH against MRSA was determined in a tape stripping mouse model of superficial skin infection for 9 days by evaluating transepidermal water loss (TEWL) and performing colony counts from cultured swabs. RESULTS: GM-EtOH showed greater in vitro activity against MRSA than GM-MeOH in broth microdilution assay with minimum inhibitory concentration 17 versus 20 MUg/mL and minimum bactericidal concentration 30 versus 35 MUg/mL, respectively. The GM-EtOH (13.20 +/- 0.49%) contained alpha-mangostin more than the GM-MeOH (9.83 +/- 0.30%). In the tape stripping mouse model, 10% GM-EtOH reduced the number of MRSA colonies (0-1) recovered from infected wounds (>100 colonies) on the first day of treatment, restored TEWL to normal levels on the fourth day, and had completely healed the wounds by day 9. CONCLUSION: GM-EtOH showed promising in vivo antibacterial activity against MRSA in a superficial skin infection model in mice. It is of interest to develop a topical formulation of GM-EtOH to further study its potential as a novel antibacterial agent. PMID- 27180762 TI - Vincristine pharmacokinetics pathway and neurotoxicity during early phases of treatment in pediatric acute lymphoblastic leukemia. AB - AIM: Vincristine is an important component of acute lymphoblastic leukemia (ALL) treatment protocols that can cause neurotoxicity. Patients treated with LAL/SHOP protocols often suffer from vincristine-related neurotoxicity in early phases of treatment. Recently, a genome-wide association study connected a SNP in CEP72, involved in vincristine pharmacodynamics, with neurotoxicity during later phases of therapy, which was not replicated during induction phase. These results, together with previous studies indicating that polymorphisms in pharmacokinetic genes are associated with drug toxicity, suggest that changes in the activity or levels of vincristine transporters or metabolizers could work as predictors of vincristine-related neurotoxicity in early phases of treatment in pediatric ALL. PATIENTS & METHODS: We analyzed 150 SNPs in eight key genes involved in vincristine pharmacokinetics and in 13 miRNAs that regulate them. We studied their correlation with neurotoxicity during induction phase in 152 ALL patients treated with LAL/SHOP protocols. RESULTS: The strongest associations with neurotoxicity were observed for two SNPs in ABCC2. The genotypes rs3740066 GG and rs12826 GG were associated with increased neurotoxicity. CONCLUSION: Polymorphisms in ABCC2 could be novel markers for vincristine-related neurotoxicity in pediatric ALL in early phases. PMID- 27180785 TI - Adherence in dermatology. AB - Non-adherence to treatment and medical recommendations is one of the leading causes of treatment failure, poor clinical outcomes, and increased healthcare utilization. Although non-adherence is observed across all medical specialties, adherence to treatment in dermatology deserves special attention given the multiple different routes of treatment. Adherence can be measured using subjective methods (patient reporting and questionnaires) or objective methods (pill counts, electronic chips, and pharmacy records). Adherence to dermatologic treatments varies based on the specific condition but is poor for systemic therapies and even worse with topical agents. Among the factors that influence adherence, duration of treatment, complexity of regimen, and access play a large role. Interventions to improve adherence can range from simplifying treatment regimens to scheduling more frequent office visits. Due to the profound effect on cost, healthcare outcomes, and mortality, understanding and improving adherence is equally as important as making the correct diagnosis and prescribing the correct treatment. PMID- 27180786 TI - The Impact of Chronic Glycogen Synthase Kinase-3 Inhibition on Remodeling of Normal and Pre-Diabetic Rat Hearts. AB - PURPOSE: There is an ongoing search for new drugs and drug targets to treat diseases like Alzheimer's disease, cancer and type 2 diabetes (T2D). Both obesity and T2D are characterized by the development of a cardiomyopathy associated with increased hypertension and compensatory left ventricular hypertrophy. Small, specific glycogen synthase kinase-3 (GSK-3) inhibitors were developed to replace lithium chloride for use in psychiatric disorders. In addition, they were advocated as treatment for T2D since GSK-3 inhibition improves blood glucose handling. However, GSK-3 is a regulator of hypertrophic signalling in the heart via phosphorylation of NFATc3 and beta-catenin respectively. In view of this, we hypothesized that chronic inhibition of GSK-3 will induce myocardial hypertrophy or exacerbate existing hypertrophy. METHODS: Rats with obesity-induced prediabetes were treated orally with GSK-3 inhibitor (CHIR118637 (CT20026)), 30 mg/kg/day for the last 8 weeks of a 20-week diet high in sugar content vs a control diet. Biometric and biochemical parameters were measured, echocardiography performed and localization and co-localization of NFATc3 and GATA4 determined in cardiomyocytes. RESULTS: Obesity initiated myocardial hypertrophy, evidenced by increased ventricular mass (1.158 +/- 0.029 vs 0.983 +/ 0.03 g) and enlarged cardiomyocytes (18.86 +/- 2.25 vs 14.92 +/- 0.50um(2)) in association with increased end-diastolic diameter (EDD = 8.48 +/- 0.11 vs 8.15 +/ 0.10 mm). GSK-3 inhibition (i) increased ventricular mass only in controls (1.075 +/- 0.022 g) and (ii) EDD in both groups (controls: 8.63 +/- 0.07; obese: 8.72 +/- 0.15 mm) (iii) localized NFATc3 and GATA4 peri-nuclearly. CONCLUSION: Indications of onset of myocardial hypertrophy in both control and obese rats treated with a GSK-3 inhibitor were found. It remains speculation whether these changes were adaptive or maladaptive. PMID- 27180788 TI - Metronidazole-Induced Encephalopathy: A Case Report. PMID- 27180787 TI - Delphinidin prevents disuse muscle atrophy and reduces stress-related gene expression. AB - Delphinidin is a member of the anthocyanidin class of plant pigments. We examined the effects of delphinidin on muscle atrophy. Oral administration of delphinidin suppressed the muscle weight loss induced by mechanical unloading. Microarray analysis showed that delphinidin suppresses the upregulation of oxidative stress related gene expression, including the expression of Cbl-b. Thus, delphinidin may prevent unloading-mediated muscle atrophy. PMID- 27180789 TI - Keloids and Hypertrophic Scars Can Now Be Cured Completely: Recent Progress in Our Understanding of the Pathogenesis of Keloids and Hypertrophic Scars and the Most Promising Current Therapeutic Strategy. AB - Keloids and hypertrophic scars are fibroproliferative disorders of the skin that are caused by abnormal healing of injured or irritated skin. It is possible that they are both manifestations of the same fibroproliferative skin disorder and just differ in terms of the intensity and duration of inflammation. These features may in turn be influenced by genetic, systemic, and local risk factors. Genetic factors may include single nucleotide polymorphisms, while systemic factors may include hypertension, pregnancy, hormones, and cytokines. The most important local factor is tension on the scar. Over the past 10 years, our understanding of the pathogenesis of keloids and hypertrophic scars has improved markedly. As a result, these previously intractable scars are now regarded as being treatable. There are many therapeutic options, including surgery, radiation, corticosteroids, 5-fluorouracil, cryotherapy, laser therapy, anti allergy agents, anti-inflammatory agents, bleaching creams and make-up therapies. However, at present, we believe that the following combination of three therapies most reliably achieves a complete cure: surgery, followed by radiation and the use of steroid tape/plaster. PMID- 27180790 TI - Different Patterns of Acetylation and Dimethylation of Histone H3 between Young and Aged Cases with Chronic Tonsillitis: Influences of Inflammation and Aging. AB - INTRODUCTION: Epigenetics is now considered to be crucially involved in normal genetics and differentiation and in pathological conditions, such as cancer, aging, and inflammation. Epigenetic mechanisms involve DNA methylation and histone modifications. The purpose of this study was to investigate the effects of inflammation on epigenetics in young subjects and the effect of aging. MATERIALS AND METHODS: The palatine tonsils were extracted from child and adult patients with chronic tonsillitis. Hematoxylin-eosin staining was performed to examine the morphology of the palatine tonsils. A fluorescence immunological examination was also performed to detect acetyl-histone H3 or dimethyl-histone H3. Confocal scanning microscopy was used for observations. RESULTS: Acetylated histone H3 was detected in tonsils from child patients but not from adult patients. Dimethylated histone H3 was not detected in tonsils from either group of patients. Degeneration of the tonsillar structures was apparent in tonsils from adult patients. DISCUSSION: The differential expression of acetylated histone H3 Lys9 may reflect immunological differences between young and aged tonsils. The decrease observed in the activity of histone methyltransferase induced the down-regulated expression of methylated histone H3. CONCLUSION: Our results suggest that epigenetic changes participate in chronic inflammation and aging in the palatine tonsils. Although the results do not lead to a direct treatment, the epigenetic pathogenesis of chronic inflammation, such as immunoglobulin A nephropathy, by focal infections will be described in greater detail in future studies, which will lead to new treatments being developed. PMID- 27180791 TI - Urgent Catheter Ablation in Octogenarians with Serious Tachyarrhythmias. AB - BACKGROUND: Urgent catheter ablation is often required for various tachyarrhythmias; however, its efficacy and safety in elderly patients have not been fully elucidated. METHODS: This study included consecutive octogenarians who underwent urgent radiofrequency catheter ablation (RFCA) for various serious tachyarrhythmias (urgent group, n=28) that were life-threatening, hemodynamically deleterious, or provoking ischemia, and consecutive octogenarians who underwent elective RFCA (control group, n=36). The rate of a successful RFCA, complications, later arrhythmia recurrences, and mortality were compared between the groups. RESULTS: There was no significant difference in the breakdown of the targeted arrhythmias between the groups, and common-type atrial flutter was most often targeted in both the urgent group (57%) and the elective group (56%). Compared with the control group patients, the patients of the urgent group were older (84+/-3 vs. 82+/-2 years P=0.001), with a higher frequency of baseline heart disease (68% vs. 17%, P<0.001) and lower left ventricular ejection fraction (45%+/-15% vs. 68%+/-10%, P<0.001). The rates of acute success (100% vs. 100%, P=1.00) and later arrhythmia recurrences (4% vs. 14%, P=0.22) were comparable between the groups. Two patients in the urgent group and 2 in the elective group had procedure-related nonlethal complications (7% vs. 6%, P=1.00): groin hematoma in 2, pressure ulcer in 1, and CO2 narcosis in 1. There were no in-hospital deaths, and mortality during follow-up did not differ between the urgent and elective groups (6.0% vs. 3.9% per year, log-rank P=0.38). CONCLUSION: Even in octogenarian patients, urgent catheter ablation for serious tachyarrhythmias can be safely performed with a high success rate and acceptable prognosis. PMID- 27180792 TI - Usefulness of Single Photon Emission Computed Tomography/Computed Tomography Fusion-Hybrid Imaging to Evaluate Coronary Artery Disorders in Patients with a History of Kawasaki Disease. AB - BACKGROUND: The coronary arterial lesions of Kawasaki disease are mainly dilative lesions, aneurysms, and stenotic lesions formed before, after, and between aneurysms; these lesions develop in multiple branches resulting in complex coronary hemodynamics. Diagnosis of myocardial ischemia and infarction and evaluation of the culprit coronary arteries and regions is critical to evaluating the treatment and prognosis of patients. This study used hybrid imaging, in which multidetector computed tomographic (CT) images for coronary CT angiography (CCTA) and stress myocardial perfusion single-photon emission CT (SPECT) images were fused. We investigated the diagnosis of blood vessels and regions responsible for myocardial ischemia and infarction in patients with complex coronary arterial lesions; in addition, we evaluated myocardial lesions that developed directly under giant coronary artery aneurysms. METHODS: The subjects were 17 patients with Kawasaki disease with multiple coronary arterial lesions (median age, 18.0 years; 16 male). Both CCTA using 64-row CT and adenosine-loading myocardial SPECT were performed. Three branches, the right coronary artery (RCA), left anterior descending branch (LAD), and left circumflex branch, were evaluated with the conventional side-by-side interpretation, in which the images were lined up for diagnosis, and hybrid imaging, in which the CCTA and SPECT images were fused with computer processing. In addition, the myocardial lesions directly under giant coronary artery aneurysms were investigated with fusion imaging. RESULTS: Images sufficient for evaluation were acquired in all 17 patients. In the RCA, coronary arterial lesions were detected with CCTA in 16 patients. The evaluations were consistent between the side-by-side and fusion interpretation in 14 patients, and the blood vessel responsible for the myocardial ischemic region was identified in 2 patients. In the left circumflex branch, coronary arterial lesions were confirmed with 3-dimensional CT in 5 patients, and the the culprit coronary arteries for myocardial ischemia/infarction were confirmed with the fusion interpretation but not with the side-by-side interpretation. In the LAD, coronary arterial lesions were present in all patients, and the diagnosis was made with the fusion interpretation in 10 patients. In the LAD, small-range infarct lesions were detected directly under the giant coronary artery aneurysm in 8 patients, but were not confirmed with the side-by-side interpretation. CONCLUSION: Fusion imaging was capable of accurately evaluating myocardial ischemia/infarction as cardiovascular sequelae of Kawasaki disease and confirming the culprit coronary arteries. In addition, analysis of fusion images confirmed that small-range infarct lesions were concomitantly present directly under giant coronary artery aneurysms in the anterior descending coronary artery. PMID- 27180793 TI - Combining Fulvestrant with Low-Dose Capecitabine is Effective and Tolerable in Woman with Metastatic Breast Cancer. AB - Although the use of endocrine therapy in combination with intravenous chemotherapy has not been standardized, the combination of fulvestrant and chemotherapy may be promising. A 62-year-old woman came to our hospital's outpatient clinic with extensive ascites. Approximately 10 years earlier, she had undergone mastectomy and sentinel lymph node biopsy. Pathologically invasive lobular carcinoma, with a maximum diameter of 28 mm, had been diagnosed in the left breast. The cancer had a histological grade of 2, was positive for estrogen receptor (95% or more positive cells), and was negative for both progesterone receptor (less than 1% positive cells) and human epidermal growth factor receptor 2. For 5 years the patient underwent adjuvant endocrine therapy with tamoxifen and then with anastrozole. Four years 2 months after adjuvant endocrine therapy had been completed, she felt abdominal distention, and her symptoms gradually worsened. A series of intensive examinations indicated that the invasive lobular carcinoma had metastasized to the peritoneum, pleura, uterus, and bone. Aromatase inhibitor was administered as a first-line therapy for the metastatic disease and was accompanied by denosumab injected every 28 days. For 2 months after the start of treatment with anastrozole, the ascites did not decrease and tumor markers increased. Because anastrozole had not been effective, fulvestrant (500 mg) and low-dose capecitabine (500 mg) were administered for the first 21 days of a 28 day cycle; this regimen had been shown by a phase 2 trial to be effective and tolerable in patients with metastatic breast cancer. The patient felt an improvement in abdominal distention, and the tumor markers decreased 2 weeks after the start of this combination therapy. By 10 months after the start of the combined therapy the ascites had decreased and pleural effusion had completely disappeared. The uterine wall became thinner, and the endometrial cavity became smaller. Tumor markers continued decreasing. No adverse events were observed. The combination of fulvestrant and low-dose capecitabine is promising because of its efficacy and tolerability for the treatment of patients with estrogen receptor positive, human epidermal growth factor receptor 2-negative metastatic breast cancer. PMID- 27180794 TI - Homonymous Hemianopsia Associated with Probable Alzheimer's Disease. AB - Posterior cortical atrophy (PCA) is a rare neurodegenerative disorder that has cerebral atrophy in the parietal, occipital, or occipitotemporal cortices and is characterized by visuospatial and visuoperceptual impairments. The most cases are pathologically compatible with Alzheimer's disease (AD). We describe a case of PCA in which a combination of imaging methods, in conjunction with symptoms and neurological and neuropsychological examinations, led to its being diagnosed and to AD being identified as its probable cause. Treatment with donepezil for 6 months mildly improved alexia symptoms, but other symptoms remained unchanged. A 59-year-old Japanese woman with progressive alexia, visual deficit, and mild memory loss was referred to our neurologic clinic for the evaluation of right homonymous hemianopsia. Our neurological examination showed alexia, constructional apraxia, mild disorientation, short-term memory loss, and right homonymous hemianopsia. These findings resulted in a score of 23 (of 30) points on the Mini-Mental State Examination. Occipital atrophy was identified, with magnetic resonance imaging (MRI) showing left-side dominance. The MRI data were quantified with voxel-based morphometry, and PCA was diagnosed on the basis of these findings. Single photon emission computed tomography with (123)I-N isopropyl-p-iodoamphetamine showed hypoperfusion in the corresponding voxel-based morphometry occipital lobes. Additionally, the finding of hypoperfusion in the posterior associate cortex, posterior cingulate gyrus, and precuneus was consistent with AD. Therefore, the PCA was considered to be a result of AD. We considered Lewy body dementia as a differential diagnosis because of the presence of hypoperfusion in the occipital lobes. However, the patient did not meet the criteria for Lewy body dementia during the course of the disease. We therefore consider including PCA in the differential diagnoses to be important for patients with visual deficit, cognitive impairment, and cerebral atrophy in the parietal, occipital, or occipitotemporal cortices. A combination of imaging methods, including MRI and single photon emission computed tomography, may help identify probable causes of PCA. PMID- 27180796 TI - Errata. PMID- 27180797 TI - Tissue Characterization of Coronary Plaques as a Key to Relationship between Serum Uric Acid Level and Cardiovascular Disease: A Direct Risk or an Indirect Marker? PMID- 27180795 TI - Right Inguinal Hernia Encompassing the Uterus, Right Ovary and Fallopian Tube in an Elderly Female: Case Report. AB - The uterus, ovary, and fallopian tube are rarely present in an inguinal hernia. We report on an operation to treat just such a rare condition for a right inguinal hernia. An 87-year-old Japanese woman was admitted with swelling in the right inguinal region and a purulent discharge from the vagina. Vital signs were stable, but the mobile mass was irreducible. Computed tomography of the abdomen indicated uterine tissue in a right inguinal hernia. We diagnosed an inguinal hernia with an incarcerated uterus and performed surgery on that basis. An incision approximately 6 cm long was made in the skin above the swollen area to open the inguinal sac, disclosing a tumor enveloped by a hernial sac. Opening the hernial sac revealed the prolapsed uterus, the fallopian tube, and the right ovary. Because no ischemic change was noted, the incarcerated uterus was returned to the abdominal cavity, and the hernial opening was closed with the onlay mesh technique. The posterior wall of the inguinal canal was found to have prolapsed laterally to the inferior epigastric artery, resulting in an external inguinal hernia. This case demonstrates that careful attention must be paid to inguinal hernias in female patients because the uterus, ovary, and fallopian tube may be involved. PMID- 27180800 TI - Ethanol extract of Cotinus coggygria leaves accelerates wound healing process in diabetic rats. AB - CONTEXT: Cotinus coggygria Scop. (Anacardiaceae) leaves that were used as wound healing in traditional Balkan and Anatolian folk medicine, could be potentially effective in treating diabetic wounds. OBJECTIVE: This study investigates biochemical and histological effects of ethanol extract of C. coggygria (CCE) on excision wound model in diabetic rats. MATERIALS AND METHODS: This study was conducted on diabetic Wistar albino rats, which were injected by a single dose (50 mg/kg i.p.) streptozotocin. Afterward an excision wound model was created in all animals; diabetic control rats were applied topically simple ointment and diabetic treatment rats were applied topically 5% (w/w) ointment with CC, once a day during the experimental period. Malondialdehyde, glutathione and hydroxyproline levels in wound tissues were investigated at the end of 3rd, 7th, and 14th days. Histopathological examination was also performed. RESULTS: Hydroxyproline content was significantly increased in the CCE treated group versus control after the 3rd and 7th days (15.33 versus 11.83; 19.67 versus 15.67 mg/g, p < 0.05; respectively). A statistically significant elevation in glutathione at the end of 3rd, 7th, and 14th days (5.13 versus 1.58, p < 0.05; 4.72 versus 1.88, p < 0.05; 3.83 versus 1.88 MUmol/g, p < 0.05, respectively) and a statistically significant decrease in malondialdehyde level at the end of 7th day (4.49 versus 1.48 nmol/g, p < 0.05) were determined in the treated group versus control group. These results were also supported by histological analyses. DISCUSSION AND CONCLUSION: These findings indicate that CCE accelerated the cutaneous wound healing process in diabetic wounds, in confirmation of its traditional use. PMID- 27180801 TI - Molecular Mechanism for Conformational Dynamics of Ras.GTP Elucidated from In Situ Structural Transition in Crystal. AB - Ras*GTP adopts two interconverting conformational states, state 1 and state 2, corresponding to inactive and active forms, respectively. However, analysis of the mechanism for state transition was hampered by the lack of the structural information on wild-type Ras state 1 despite its fundamental nature conserved in the Ras superfamily. Here we solve two new crystal structures of wild-type H-Ras, corresponding to state 1 and state 2. The state 2 structure seems to represent an intermediate of state transition and, intriguingly, the state 1 crystal is successfully derived from this state 2 crystal by regulating the surrounding humidity. Structural comparison enables us to infer the molecular mechanism for state transition, during which a wide range of hydrogen-bonding networks across Switch I, Switch II and the alpha3-helix interdependently undergo gross rearrangements, where fluctuation of Tyr32, translocation of Gln61, loss of the functional water molecules and positional shift of GTP play major roles. The NMR based hydrogen/deuterium exchange experiments also support this transition mechanism. Moreover, the unveiled structural features together with the results of the biochemical study provide a new insight into the physiological role of state 1 as a stable pool of Ras*GTP in the GDP/GTP cycle of Ras. PMID- 27180802 TI - Sepsis in preterm infants causes alterations in mucosal gene expression and microbiota profiles compared to non-septic twins. AB - Sepsis is a life-threatening condition in preterm infants. Neonatal microbiota plays a pivotal role in the immune system maturation. Changes in gut microbiota have been associated to inflammatory disorders; however, a link with sepsis in the neonatal period has not yet been established. We aimed to analyze gut microbiota and mucosal gene expression using non-invasively obtained samples to provide with an integrative perspective of host-microbe interactions in neonatal sepsis. For this purpose, a prospective observational case-control study was conducted in septic preterm dizygotic twins and their non-septic twin controls. Fecal samples were used for both microbiota analysis and host genome-wide expression using exfoliated intestinal cells. Gene expression of exfoliated intestinal cells in septic preterm showed an induction of inflammatory and oxidative stress pathways in the gut and pro-oxidant profile that caused dysbiosis in the gut microbiota with predominance of Enterobacteria and reduction of Bacteroides and Bifidobacterium spp.in fecal samples, leading to a global reduction of beneficial anaerobic bacteria. Sepsis in preterm infants induced low grade inflammation and oxidative stress in the gut mucosa, and also changes in the gut microbiota. This study highlights the role of inflammation and oxidative stress in neonatal sepsis on gut microbial profiles. PMID- 27180803 TI - TGF-beta Signaling Regulates Cementum Formation through Osterix Expression. AB - TGF-beta/BMPs have widely recognized roles in mammalian development, including in bone and tooth formation. To define the functional relevance of the autonomous requirement for TGF-beta signaling in mouse tooth development, we analyzed osteocalcin-Cre mediated Tgfbr2 (OC(Cre)Tgfbr2(fl/fl)) conditional knockout mice, which lacks functional TGF-beta receptor II (TbetaRII) in differentiating cementoblasts and cementocytes. Strikingly, OC(Cre)Tgfbr2(fl/fl) mutant mice exhibited a sharp reduction in cellular cementum mass with reduced matrix secretion and mineral apposition rates. To explore the molecular mechanisms underlying the roles of TGF-beta signaling through TbetaRII in cementogenesis, we established a mouse cementoblast model with decreased TbetaRII expression using OCCM-30 cells. Interestingly, the expression of osterix (Osx), one of the major regulators of cellular cementum formation, was largely decreased in OCCM-30 cells lacking TbetaRII. Consequently, in those cells, functional ALP activity and the expression of genes associated with cementogenesis were reduced and the cells were partially rescued by Osx transduction. We also found that TGF-beta signaling directly regulates Osx expression through a Smad-dependent pathway. These findings strongly suggest that TGF-beta signaling plays a major role as one of the upstream regulators of Osx in cementoblast differentiation and cementum formation. PMID- 27180805 TI - Fast machine-learning online optimization of ultra-cold-atom experiments. AB - We apply an online optimization process based on machine learning to the production of Bose-Einstein condensates (BEC). BEC is typically created with an exponential evaporation ramp that is optimal for ergodic dynamics with two-body s wave interactions and no other loss rates, but likely sub-optimal for real experiments. Through repeated machine-controlled scientific experimentation and observations our 'learner' discovers an optimal evaporation ramp for BEC production. In contrast to previous work, our learner uses a Gaussian process to develop a statistical model of the relationship between the parameters it controls and the quality of the BEC produced. We demonstrate that the Gaussian process machine learner is able to discover a ramp that produces high quality BECs in 10 times fewer iterations than a previously used online optimization technique. Furthermore, we show the internal model developed can be used to determine which parameters are essential in BEC creation and which are unimportant, providing insight into the optimization process of the system. PMID- 27180804 TI - Rearrangement of mitochondrial tRNA genes in flat bugs (Hemiptera: Aradidae). AB - The typical insect mitochondrial (mt) genome organization, which contains a single chromosome with 37 genes, was found in the infraorder Pentatomomorpha (suborder Heteroptera). The arrangement of mt genes in these true bugs is usually the same as the ancestral mt gene arrangement of insects. Rearrangement of transfer RNA (tRNA) genes, however, has been found in two subfamilies of flat bugs (Mezirinae and Calisiinae, family Aradidae). In this study, we sequenced the complete mt genomes of four species from three other subfamilies (Aradinae, Carventinae and Aneurinae). We found tRNA gene rearrangement in all of these four species. All of the rearranged tRNA genes are located between the mitochondrial control region and cox1, indicating this region as a hotspot for gene rearrangement in flat bugs; the rearrangement is likely caused by events of tandem duplication and random deletion of genes. Furthermore, our phylogenetic and dating analyses indicated that the swap of positions between trnQ and trnI occurred ~162 million years ago (MYA) in the most recent common ancestor of the five subfamilies of flat bugs investigated to date, whereas the swap of positions between trnC and trnW occurred later in the lineage leading to Calisiinae, and the translocation of trnC and trnY occurred later than 134 MYA in the lineage leading to Aradinae. PMID- 27180806 TI - The fast-recycling receptor Megalin defines the apical recycling pathway of epithelial cells. AB - The basolateral recycling and transcytotic pathways of epithelial cells were previously defined using markers such as transferrin (TfR) and polymeric IgA (pIgR) receptors. In contrast, our knowledge of the apical recycling pathway remains fragmentary. Here we utilize quantitative live-imaging and mathematical modelling to outline the recycling pathway of Megalin (LRP-2), an apical receptor with key developmental and renal functions, in MDCK cells. We show that, like TfR, Megalin is a long-lived and fast-recycling receptor. Megalin enters polarized MDCK cells through segregated apical sorting endosomes and subsequently intersects the TfR and pIgR pathways at a perinuclear Rab11-negative compartment termed common recycling endosomes (CRE). Whereas TfR recycles to the basolateral membrane from CRE, Megalin, like pIgR, traffics to subapical Rab11-positive apical recycling endosomes (ARE) and reaches the apical membrane in a microtubule and Rab11-dependent manner. Hence, Megalin defines the apical recycling pathway of epithelia, with CRE as its apical sorting station. PMID- 27180807 TI - Differential neuronal vulnerability identifies IGF-2 as a protective factor in ALS. AB - The fatal disease amyotrophic lateral sclerosis (ALS) is characterized by the loss of somatic motor neurons leading to muscle wasting and paralysis. However, motor neurons in the oculomotor nucleus, controlling eye movement, are for unknown reasons spared. We found that insulin-like growth factor 2 (IGF-2) was maintained in oculomotor neurons in ALS and thus could play a role in oculomotor resistance in this disease. We also showed that IGF-1 receptor (IGF-1R), which mediates survival pathways upon IGF binding, was highly expressed in oculomotor neurons and on extraocular muscle endplate. The addition of IGF-2 induced Akt phosphorylation, glycogen synthase kinase-3beta phosphorylation and beta-catenin levels while protecting ALS patient motor neurons. IGF-2 also rescued motor neurons derived from spinal muscular atrophy (SMA) patients from degeneration. Finally, AAV9::IGF-2 delivery to muscles of SOD1(G93A) ALS mice extended life span by 10%, while preserving motor neurons and inducing motor axon regeneration. Thus, our studies demonstrate that oculomotor-specific expression can be utilized to identify candidates that protect vulnerable motor neurons from degeneration. PMID- 27180808 TI - The spin-dependent transport properties of zigzag alpha-graphyne nanoribbons and new device design. AB - By performing first-principle quantum transport calculations, we studied the electronic and transport properties of zigzag alpha-graphyne nanoribbons in different magnetic configurations. We designed the device based on zigzag alpha graphyne nanoribbon and studied the spin-dependent transport properties, whose current-voltage curves show obvious spin-polarization and conductance plateaus. The interesting transport behaviours can be explained by the transport spectra under different magnetic configurations, which basically depends on the symmetry matching of the electrodes' bandstructures. Simultaneously, spin Seebeck effect is also found in the device. Thus, according to the transport behaviours, zigzag alpha-graphyne nanoribbons can be used as a dual spin filter diode, a molecule signal converter and a spin caloritronics device, which indicates that alpha graphyne is a promising candidate for the future application in spintronics. PMID- 27180809 TI - microRNA expression profiling on individual breast cancer patients identifies novel panel of circulating microRNA for early detection. AB - Breast cancer (BC) is the most common cancer type and the second cause of cancer related death among women. Therefore, better understanding of breast cancer tumor biology and the identification of novel biomarkers is essential for the early diagnosis and for better disease stratification and management choices. Herein we developed a novel approach which relies on the isolation of circulating microRNAs through an enrichment step using speed-vacuum concentration which resulted in 5 fold increase in microRNA abundance. Global miRNA microarray expression profiling performed on individual samples from 23 BC and 9 normals identified 18 up regulated miRNAs in BC patients (p(corr) < 0.05). Nine miRNAs (hsa-miR-4270, hsa miR-1225-5p, hsa-miR-188-5p, hsa-miR-1202, hsa-miR-4281, hsa-miR-1207-5p, hsa-miR 642b-3p, hsa-miR-1290, and hsa-miR-3141) were subsequently validated using qRT PCR in a cohort of 46 BC and 14 controls. The expression of those microRNAs was overall higher in patients with stage I, II, and III, compared to stage IV, with potential utilization for early detection. The expression of this microRNA panel was slightly higher in the HER2 and TN compared to patients with luminal subtype. Therefore, we developed a novel approach which led to the identification of a novel microRNA panel which was upregulated in BC patients with potential utilization in disease diagnosis and stratification. PMID- 27180810 TI - The functional role of time compression. AB - Multisensory integration provides continuous and stable perception from separate sensory inputs. Here, we investigated the functional role of temporal binding between the visual and the tactile senses. To this end we used the paradigm of compression that induces shifts in time when probe stimuli are degraded, e.g., by a visual mask (Zimmermann et al. 2014). Subjects had to estimate the duration of temporal intervals of 500 ms defined by a tactile and a visual, masked stimulus. We observed a strong (~100 ms) underestimation of the temporal interval when the stimuli from both senses appeared to occur at the same position in space. In contrast, when the positions of the visual and tactile stimuli were spatially separate, interval perception was almost veridical. Temporal compression furthermore depended on the correspondence of probe features and was absent when the orientation of the tactile and visual probes was incongruent. An additional experiment revealed that temporal compression also occurs when objects were presented outside the attentional focus. In conclusion, these data support a role for spatiotemporal binding in temporal compression, which is at least in part selective for object features. PMID- 27180811 TI - Early clearance of Chikungunya virus in children is associated with a strong innate immune response. AB - Chikungunya fever (CHIKF) is a global infectious disease which can affect a wide range of age groups. The pathological and immunological response upon Chikungunya virus (CHIKV) infection have been reported over the last few years. However, the clinical profile and immune response upon CHIKV infection in children remain largely unknown. In this study, we analyzed the clinical and immunological response, focusing on the cytokine/chemokine profile in a CHIKV-infected pediatric cohort from Sarawak, Malaysia. Unique immune mediators triggered upon CHIKV infection were identified through meta-analysis of the immune signatures between this pediatric group and cohorts from previous outbreaks. The data generated from this study revealed that a broad spectrum of cytokines/chemokines is up-regulated in a sub-group of virus-infected children stratified according to their viremic status during hospitalization. Furthermore, different immune mediator profiles (the levels of pro-inflammatory cytokines, chemokines and growth and other factors) were observed between children and adults. This study gives an important insight to understand the immune response of CHIKV infection in children and would aid in the development of better prognostics and clinical management for children. PMID- 27180812 TI - Inflammation: Inflammatory pathology of Fanconi anaemia. PMID- 27180813 TI - Innate immunity: Sensing broken antibody. PMID- 27180814 TI - Lymphocyte responses: Hunker down with HOBIT and BLIMP1. PMID- 27180816 TI - Fetal gastroschisis: antepartum fetal heart rate analysis by computerized cardiotocography. AB - OBJECTIVES: To describe the antenatal fetal heart rate (FHR) parameters analyzed by computerizedcardiotocography (cCTG) in fetuses with gastroschisis and compare the FHR parameters with ultrasound gastrointestinal markers. METHODS: A retrospective analysis of antepartum cCTG records were conducted in 87 pregnant cases with fetal gastroschisis between 28and 36 weeks (plus 6 days). A comparative analysis of the median distribution of the following FHR parameters was performed: basal FHR, short-term variation (STV), FHR accelerations and decelerations, episodes of high and low variations, and variations in low and high episodes. FHR parameters and ultrasound gastrointestinal markers were also compared. RESULTS: The majority of FHR parameters did not present significant changes throughout gestation. An increased number of records with episodes of low variation (p = 0.019) and an increased number of accelerations >15 bpm (p = 0.001) were the only observed changes throughout gestation. Stomach herniation was significantly associated with a lower STV (p = 0.018) and a higher frequency of records with low episodes (p = 0.049). CONCLUSIONS: The cCTG analysis indicated that the FHR parameters in fetuses with gastroschisis presented different patterns from those observed in normal fetuses. Stomach herniation was associated with altered FHR patterns. PMID- 27180815 TI - Adiponectin plays a role in energy metabolism for musk secretion in scent glands of muskrats (Ondatra zibethicus). AB - Adult male muskrats (Ondatra zibethicus) secret musk from their scent glands to attract females for seasonal mating. The goal of the present study was to investigate whether the changes in energy metabolism related to musk secretion during the breeding and non-breeding seasons are mediated by adiponectin. We found that the secretion of musk during the breeding season was markedly greater than that during the non-breeding season. The serum adiponectin concentration measured using an ELISA kit was higher during the breeding season than during the non-breeding season. Glandular cells, interstitial cells, epithelial cells and glandular cavities were detected in scent glands using histological methods. Immunohistochemical methods were used to show that AMP-activated protein kinase gamma-1 (AMPKG1), and glucose transporter 1 (GLUT1) were more strongly expressed in glandular cells during the breeding season than the non-breeding season, whereas the immunoreactivity for acetyl-CoA carboxylase 1 (ACC1) was stronger during the non-breeding season. Consistent with these qualitative results, RNA Seq analysis indicated that the expression of AdipoR1 mRNA was not significantly different during the two seasons. However, AMPKG1 and GLUT1 mRNA levels were higher in scent glands during the breeding season than during the non-breeding season, whereas ACC1 mRNA levels notably decreased during the breeding season. These results suggest that greater musk secretion requires additional energy, which may be provided by an adiponectin-mediated increase in beta-oxidation and glucose absorption. PMID- 27180817 TI - Global quantitative proteomics reveal up-regulation of endoplasmic reticulum stress response proteins upon depletion of eIF5A in HeLa cells. AB - The eukaryotic translation factor, eIF5A, is a translation factor essential for protein synthesis, cell growth and animal development. By use of a adenoviral eIF5A shRNA, we have achieved an effective depletion of eIF5A in HeLa cells and undertook in vivo comprehensive proteomic analyses to examine the effects of eIF5A depletion on the total proteome and to identify cellular pathways influenced by eIF5A. The proteome of HeLa cells transduced with eIF5A shRNA was compared with that of scramble shRNA-transduced counterpart by the iTRAQ method. We identified 972 proteins consistently detected in three iTRAQ experiments and 104 proteins with significantly altered levels (protein ratio >=1.5 or <=0.66, p value <=0.05) at 72 h and/or 96 h of Ad-eIF5A-shRNA transduction. The altered expression levels of key pathway proteins were validated by western blotting. Integration of functional ontology with expression data of the 104 proteins revealed specific biological processes that are prominently up- or down regulated. Heatmap analysis and Cytoscape visualization of biological networks identified protein folding as the major cellular process affected by depletion of eIF5A. Our unbiased, quantitative, proteomic data demonstrate that the depletion of eIF5A leads to endoplasmic reticulum stress, an unfolded protein response and up-regulation of chaperone expression in HeLa cells. PMID- 27180818 TI - Long-Term Maintenance of Physical Function in Older Adults Following a DVD Delivered Exercise Intervention. AB - Previous evidence suggests physical activity interventions effectively produce short-term improvements in physical function for older adults. The present study examined whether improvements in physical function after a DVD-delivered exercise intervention were maintained 18 months postintervention. Older adults (n = 153) randomized to a 6-month DVD-delivered exercise intervention or an attentional control condition were contacted 18 months postintervention. Participants completed the Short Physical Performance Battery (SPPB) and measures of flexibility, strength, and functional limitations were taken. Analyses of variance were conducted to determine if improvements in physical function as a result of the intervention were maintained at follow-up. Improvements in the SPPB, F (1,125) = 3.70, p = .06, eta2 = .03, and upper body strength, F (1,121) = 3.04, p = .08, eta2 = .03 were maintained for the intervention condition. Home based DVD exercise training interventions may hold promise for long-term maintenance of physical function in older adults. PMID- 27180819 TI - Impact of Leaf Removal, Applied Before and After Flowering, on Anthocyanin, Tannin, and Methoxypyrazine Concentrations in 'Merlot' (Vitis vinifera L.) Grapes and Wines. AB - The development and accumulation of secondary metabolites in grapes determine wine color, taste, and aroma. This study aimed to investigate the effect of leaf removal before flowering, a practice recently introduced to reduce cluster compactness and Botrytis rot, on anthocyanin, tannin, and methoxypyrazine concentrations in 'Merlot' grapes and wines. Leaf removal before flowering was compared with leaf removal after flowering and an untreated control. No effects on tannin and anthocyanin concentrations in grapes were observed. Both treatments reduced levels of 3-isobutyl-2-methoxypyrazine (IBMP) in the grapes and the derived wines, although the after-flowering treatment did so to a greater degree in the fruit specifically. Leaf removal before flowering can be used to reduce cluster compactness, Botrytis rot, and grape and wine IBMP concentration and to improve wine color intensity but at the expense of cluster weight and vine yield. Leaf removal after flowering accomplishes essentially the same results without loss of yield. PMID- 27180820 TI - Thermally Reduced Graphene Oxide Electrochemically Activated by Bis-Spiro Quaternary Alkyl Ammonium for Capacitors. AB - Thermally reduced graphene oxide (RGO) electrochemically activated by a quaternary alkyl ammonium-based organic electrolytes/activated carbon (AC) electrode asymmetric capacitor is proposed. The electrochemical activation process includes adsorption of anions into the pores of AC in the positive electrode and the interlayer intercalation of cations into RGO in the negative electrode under high potential (4.0 V). The EA process of RGO by quaternary alkyl ammonium was investigated by X-ray diffraction and electrochemical measurements, and the effects of cation size and structure were extensively evaluated. Intercalation by quaternary alkyl ammonium demonstrates a small degree of expansion of the whole crystal lattice (d002) and a large degree of expansion of the partial crystal lattice (d002) of RGO. RGO electrochemically activated by bis spiro quaternary alkyl ammonium in propylene carbonate/AC asymmetric capacitor exhibits good activated efficiency, high specific capacity, and stable cyclability. PMID- 27180821 TI - Emergency Department Visits after Diagnosed Chronic Obstructive Pulmonary Disease in Aboriginal People in Alberta, Canada. AB - OBJECTIVES: This retrospective cohort study compared rates of emergency department (ED) visits after a diagnosis of chronic obstructive pulmonary disease (COPD) in the three Aboriginal groups (Registered First Nations, Metis and Inuit) relative to a non-Aboriginal cohort. METHODS: We linked eight years of administrative health data from Alberta and calculated age- and sex-standardized ED visit rates in cohorts of Aboriginal and non-Aboriginal individuals diagnosed with COPD. Rate ratios (RR) with 95% confidence intervals (CIs) were calculated in a Poisson regression model that adjusted for important sociodemographic factors and comorbidities. Differences in ED length of stay (LOS) and disposition status were also evaluated. RESULTS: A total of 2,274 Aboriginal people and 1,611 non-Aboriginals were newly diagnosed with COPD during the study period. After adjusting for important sociodemographic and clinical factors, the rate of all cause ED visits in all Aboriginal people (RR=1.72, 95% CI: 1.67, 1.77), particularly among Registered First Nations people (RR=2.02; 95% CI: 1.97, 2.08) and Inuit (RR=1.28; 95% CI: 1.22, 1.35), were significantly higher than that in non-Aboriginals, while ED visit rates were significantly lower in the Metis (RR=0.94; 95% CI: 0.90, 0.98). The ED LOS in all Aboriginal groups were significantly lower than that of the non-Aboriginal group. CONCLUSIONS: Aboriginal people with COPD use almost twice the amount of ED services compared to their non-Aboriginal counterparts. There are also important variations in patterns of ED services use among different Aboriginal groups with COPD in Alberta. PMID- 27180822 TI - Silver Iodide-Chitosan Nanotag Induced Biocatalytic Precipitation for Self Enhanced Ultrasensitive Photocathodic Immunosensor. AB - In this work, we first exposed that the application of p-type semiconductor, silver iodide-chitosan nanoparticle (SICNP), acted as peroxidase mimetic to catalyze the bioprecipitation reaction for signal-amplification photocathodic immunosensing of human interleukin-6 (IL-6). After immobilization of captured antibody onto a polyethylenimine-functionalized carbon nitride (CN) matrix, SICNPs as photoactive tags and peroxidase mimetics were labeled on secondary antibodies, which were subsequently introduced onto the sensing interface to construct sandwich immunoassay platform through antigen-antibody specific recognition. Due to the matched energy levels between CN and AgI, the photocurrent intensity and photostability of SICNP were dramatically improved with rapid separation and transportation of photogenerated carriers. Moreover, the insoluble product in effective biocatalytic precipitation reaction served as electron acceptor to scavenge the photoexcited electron, leading to great amplification of the photocurrent signal of SICNP again. With the help of multiamplification processes, this photocathodic immunosensor presented a turn-on photoelectrochemical performance for IL-6, which showed wide linear dynamic range from 10(-6) to 10 pg/mL with the ultralow detection limit of 0.737 ag/mL. This work also performed the promising application of SICNP in developing an ultrasensitive, cost-effective, and enzyme-free photocathodic immunosensor for biomarkers. PMID- 27180824 TI - COI-based DNA barcoding of some species of Pentatomidae from North India (Hemiptera: Heteroptera). AB - The family Pentatomidae is one of the largest families of the sub-order Heteroptera, comprising 4722 species belonging to 896 genera. In the present paper, we analysed a partial ~600 bp COI sequence of 14 species of family Pentatomidae, collected from northern part of India. For seven species viz., Tolumnia antennata Distant, 1902, Cahara jugatoria (Lethierry, 1891), Bagrada hilaris (Burmeister, 1835), Plautia viridicollis (Westwood, 1837), Priassus exemptus (Walker, 1868), Dalpada neoclavata (Rider, 1998) and Dalpada affinis (Dallas, 1851), this is the first ever molecular study which has generated distinct barcodes for each. The COI sequences of these seven species have been added to the existing database at GenBank NCBI which can be used for their identification. The database analysis shows mean K2P divergence of 2.5% at intraspecific level, 11.9% at interspecific level and 16.37% at intergeneric level, thereby indicating a hierarchical increase in K2P mean divergence across different taxonomic levels. PMID- 27180825 TI - In vitro characterization of belinostat glucuronidation: demonstration of both UGT1A1 and UGT2B7 as the main contributing isozymes. AB - 1. Belinostat is a histone deacetylase inhibitor that has been approved for the treatment of peripheral T-cell lymphoma. This study aimed to identify the UDP glucuronosyltransferase (UGT) enzymes responsible for belinostat glucuronidation through kinetic determination using recombinant enzymes with determined enzyme concentrations. 2. The rate of glucuronidation was determined by incubation of belinostat with enzyme preparations. Kinetic parameters such as Km and Vmax were derived by fitting an appropriate model to the glucuronidation data. The role of active UGT enzymes to belinostat metabolism was evaluated using inhibition experiments and activity correlation analyses. 3. Human liver microsomes generated a glucuronide metabolite (i.e. belinostat glucuronide) from belinostat. The glucuronide structure was confirmed by high-resolution mass spectrometry as well as the fragmentation pattern. Of 12 test UGT enzymes, only four (UGT1A1, 1A3, 2B4, and 2B7) showed metabolic activities toward belinostat. UGT1A1 was the most active enzyme, followed by UGT2B7, 1A3, and 2B4. Kinetic profiles for UGT1A1, 1A3, 2B4, and 2B7 were well described by Michaelis-Menten, Michaelis Menten, Hill equation, and substrate inhibition equation, respectively. 4. Glucuronidation of belinostat was markedly inhibited by emodin and apigenin (two potent inhibitors of UGT1A1), and by quinidine and diclofenac sodium (two selective inhibitors of UGT2B7). Belinostat glucuronidation was found to be significantly correlated with beta-estradiol 3-O-glucuronidation and zidovudine glucuronidation. 5. It was concluded that in addition to UGT1A1, UGT2B7 was also an important contributor to belinostat glucuronidation. PMID- 27180826 TI - A mixed-methods impact evaluation of the feasibility of an initiative in small rural stores to improve access to fruit and vegetables. AB - Retail stores are a promising setting for improving access to nutritious food. This study opportunistically evaluated an initiative that supported stores in small rural Victorian towns to sell fresh fruit and vegetables. It aimed to measure whether the initiative showed a trend towards improved access to fruit and vegetables in these rural communities. A mixed-methods, pre-post evaluation was employed to measure the range and price of 39 fruits and 45 vegetables, together with 15 interviews with stakeholders 2.5 years after the commencement of the initiative. Twenty-one of 35 eligible stores took up the initiative. Analysis of qualitative and quantitative data showed that the initiative improved the availability of and access to fruit and vegetables, and that stores have a role in improving access to fruit and vegetables. The overall range of fruit and vegetables increased over 18 months from a median of 10 varieties (n=10) to 17 varieties (n=15) (P=0.028) and the prices decreased over 12 months in five out of seven stores where data was available. The capacity to influence availability of fruit and vegetables was affected by time, human resources and community support. Sustaining change to fruit and vegetables access is challenging. Using stores for health promotion may be an effective strategy for improving rural populations' fruit and vegetable intake. PMID- 27180823 TI - Higher organism load associated with failure of azithromycin to treat rectal chlamydia. AB - Repeat rectal chlamydia infection is common in men who have sex with men (MSM) following treatment with 1 g azithromycin. This study describes the association between organism load and repeat rectal chlamydia infection, genovar distribution, and efficacy of azithromycin in asymptomatic MSM. Stored rectal chlamydia-positive samples from MSM were analysed for organism load and genotyped to assist differentiation between reinfection and treatment failure. Included men had follow-up tests within 100 days of index infection. Lymphogranuloma venereum and proctitis diagnosed symptomatically were excluded. Factors associated with repeat infection, treatment failure and reinfection were investigated. In total, 227 MSM were included - 64 with repeat infections [28.2%, 95% confidence interval (CI) 22.4-34.5]. Repeat positivity was associated with increased pre-treatment organism load [odds ratio (OR) 1.7, 95% CI 1.4-2.2]. Of 64 repeat infections, 29 (12.8%, 95% CI 8.7-17.8) were treatment failures and 35 (15.4%, 95% CI 11.0-20.8) were reinfections, 11 (17.2%, 95% CI 8.9-28.7) of which were definite reinfections. Treatment failure and reinfection were both associated with increased load (OR 2.0, 95% CI 1.4-2.7 and 1.6, 95% CI 1.2-2.2, respectively). The most prevalent genovars were G, D and J. Treatment efficacy for 1 g azithromycin was 83.6% (95% CI 77.2-88.8). Repeat positivity was associated with high pre-treatment organism load. Randomized controlled trials are urgently needed to evaluate azithromycin's efficacy and whether extended doses can overcome rectal infections with high organism load. PMID- 27180827 TI - POTENTIAL CONTRIBUTION OF ADULT POPULATIONS TO THE MAINTENANCE OF SCHISTOSOMIASIS AND SOIL-TRANSMITTED HELMINTH INFECTIONS IN THE SIAVONGA AND MAZABUKA DISTRICTS OF ZAMBIA. AB - A majority of Zambian children live in impoverished communities that lack safe water and proper sanitation, exposing them to urogenital and intestinal helminths. Efforts to mitigate this plight have been implemented through mass drug administration aimed at deworming school-age and under-five children against schistosomiasis and soil-transmitted helminths. However, the disease status of adults living in the same communities as the treated children remains unknown. The aim of this study was to describe the potential contribution of infected adult populations to the transmission of these infections in southern Zambia. A cross-sectional study was conducted in April and May 2013 as part of baseline survey for a larger study in Mazabuka and Siavonga Districts. Stool and urine samples of 2829 adults from five catchment areas were collected and processed using Kato-Katz and urine filtration methods, respectively. Adults from Siavonga had a 13.9% combined prevalence of Schistosoma haematobium and S. mansoni, and 12.1% combined prevalence of Ascaris lumbricoides and hookworm. There was no S. mansoni in Mazabuka, and only a 5.3% prevalence of S. haematobium and 7.4% combined prevalence of A. lumbricoides and hookworm. Additionally, no Trichuris trichiura infections were observed in the two districts. Despite most of these infections being categorized as light intensity, heavy infection intensities were also found for all four parasite species. If this infected adult population is left untreated, the possibility of it acting as a reservoir of infections and ultimately transmitting the infections to treated children remains. Therefore, there is need to consider alternative treatment strategies that incorporate adults, thereby reducing the risk of contaminating the environment and perpetuating transmission to children. PMID- 27180828 TI - An Anatomical Study of the Nutrient Foramina of the Human Humeral Diaphysis. AB - BACKGROUND Understanding the nutrient foramina is critical to clinical practice. An insult to the nutrient foramina can be caused by trauma and/or surgical dissection and lead to devascularization and bad outcomes. Few studies have looked at the humerus, and no studies have described relative information of humeral nutrient foramen related to anatomical structures that might be located by palpable landmarks. In this study, we analyzed the anatomical features of the nutrient foramina of the diaphyseal humerus and provide a discussion of clinical relevance. MATERIAL AND METHODS We dissected 19 cadavers and analyzed the relative positions of the foramina and surrounding muscles, and the number, direction, diameter, and location of the nutrient foramina. Foramina index and a new landmark index were used to calculate the location. We compared the data from both sides and the relationships between transverse and longitudinal locations, diameter and total length, and foramina index and landmark index were also analyzed. RESULTS The humeri had one or two main nutrient foramina located in a small area between the coracobrachialis and brachial muscles and oriented toward the elbow. The mean diameter was 1.11+/-0.32 mm. The mean index and landmark index were 43.76+/-4.94% and 42.26+/-5.35%, respectively. There were no differences between sides in terms of diameter, length, or nutrient foramina index. There were no significant correlations between transverse and longitudinal locations or diameter and total length. The foramina index and landmark index showed strong positive correlation (r=0.994, p<0.0001). CONCLUSIONS Our study provides details about the nutrient foramina that will benefit clinicians who treat injuries and diseases of the humerus. Surgeons should be mindful of soft tissue in the foraminal area during surgical procedures. PMID- 27180831 TI - Previously reported PDE3A-SLCO1C1 genetic variant does not correlate with anti TNF response in a large UK rheumatoid arthritis cohort. AB - AIM: A genetic variant has recently reached genome-wide significance for association with TNF-inhibitor response in rheumatoid arthritis patients. Here we undertake a replication study in a UK Caucasian population to test for association with TNF-inhibitor response. MATERIALS & METHODS: The genetic variant, rs3794271, located within the PDE3A-SLCO1C1 locus was analyzed for correlation with treatment response using both the EULAR classification criteria and absolute change in (Delta)DAS28 scores as outcome measures. RESULTS: Genotype data were available from 1750 TNF-inhibitor treated individuals. However, no evidence for association was observed (EULAR: p = 0.91 and DeltaDAS28: p = 0.93). Furthermore, no significant associations were observed upon stratification by the anti-TNF received (p > 0.05). CONCLUSION: In the largest replication cohort conducted to date, no evidence for association was observed. PMID- 27180832 TI - The use of routine EEG in acute ischemic stroke patients without seizures: generalized but not focal EEG pathology is associated with clinical deterioration. AB - PURPOSE: Specialized electroencephalography (EEG) methods have been used to provide clues about stroke features and prognosis. However, the value of routine EEG in stroke patients without (suspected) seizures has been somewhat neglected. We aimed to assess this in a group of acute ischemic stroke patients in regard to short-term prognosis and basic stroke features. METHODS: We assessed routine (10 20) EEG findings in 69 consecutive acute ischemic stroke patients without seizures. Associations between EEG abnormalities and NIHSS scores, clinical improvement or deterioration as well as MRI stroke characteristics were evaluated. RESULTS: Mean age was 69 +/- 18 years, 43 of the patients (62.3%) were men. Abnormal EEG was found in 40 patients (58%) and was associated with higher age (p = 0.021). The most common EEG pathology was focal slowing (30; 43.5%). No epileptiform potentials were found. Abnormal EEG in general and generalized or focal slowing in particular was significantly associated with higher NIHSS score on admission and discharge as well as with hemorrhagic transformation of the ischemic lesion. Abnormal EEG and generalized (but not focal) slowing were associated with clinical deterioration ( p = 0.036, p = 0.003). Patients with lacunar strokes had no EEG abnormalities. CONCLUSIONS: Abnormal EEG in general and generalized slowing in particular are associated with clinical deterioration after acute ischemic stroke. The study demonstrates the value of routine EEG as a simple diagnostic tool in the evaluation of stroke patients especially with regard to short-term prognosis. PMID- 27180833 TI - Synthesis and formation mechanistic investigation of nitrogen-doped carbon dots with high quantum yields and yellowish-green fluorescence. AB - Heteroatom doped carbon dots (CDs) have received increasing attention due to their unique properties and related applications. However, previously reported CDs generally show strong emission only in the blue-light region, thus restricting their further applications. And the fundamental investigation on the preparation process is always neglected. Herein, we have developed a simple and solvent-free synthetic strategy to fabricate nitrogen-doped CDs (N-CDs) from citric acid and dicyandiamide. The as-prepared N-CDs exhibited a uniform size distribution, strong yellowish-green fluorescence emission and a high quantum yield of 73.2%. The products obtained at different formation stages were detailedly characterized by transmission electron microscopy, X-ray diffraction spectrometer, X-ray photoelectron spectroscopy and UV absorbance spectroscopy. A possible formation mechanism has thus been proposed including dehydration, polymerization and carbonization. Furthermore, the N-CDs could serve as a facile and label-free probe for the detection of iron and fluorine ions with detection limits of 50 nmol L(-1) and 75 nmol L(-1), respectively. PMID- 27180834 TI - Comparison of collagen content in skin wounds evaluated by biochemical assay and by computer-aided histomorphometric analysis. AB - CONTEXT: The quantification of total collagen is of major importance in a wide range of research areas, including the study of cutaneous wound healing and new drugs trials. OBJECTIVE: The total collagen content in skin biopsies was compared by biochemical hydroxyproline assay and by two computer-aided histomorphometric analyses of histological sections. MATERIALS AND METHODS: Two methods were used to evaluate collagen formation: the hydroxyproline assay, as the gold standard and histomorphometric image analysis of the filled areas by corresponding stained collagen fibres, using picrosirius and Gomori's trichrome staining. The image analyses were determined by digital densitometry recognition using computer-aided ImageJ software. One-way ANOVA, simple linear regression and ANCOVA were applied for the statistical analysis and correlation. RESULTS: In a simple linear regression analysis carried out on the 14th day period after the induction of skin injury, three techniques, picrosirius red (F = 33.57, p = 0.00), Gomori's trichrome (F = 81.61, p = 0.00) and hydroxyproline content (F = 16.85, p = 0.00) were able to detect collagen production. After scale adjustment, there were no significant differences among either the slopes (F = 1.17, p = 0.32) or the intercepts (F = 0.69, p = 0.51) of the estimated regression lines. It seems that a highly significant correlation exists between the histomorphometrical analysis and hydroxyproline assay. DISCUSSION AND CONCLUSION: The morphometric analysis proved to be adequate and can be used as a simple, rapid, low-cost technology for evaluating total collagen in cutaneous wound specimens, compared with the gold standard hydroxyproline assay. PMID- 27180835 TI - The removal of organic precursors of DBPs during three advanced water treatment processes including ultrafiltration, biofiltration, and ozonation. AB - The removal efficiency of organic matter, the formation potential of trihalomethanes (THMFP), and the formation potential of haloacetic acids (HAAFP) in each unit of three advanced treatment processes were investigated in this paper. The molecular weight distribution and the components of organic matter in water samples were also determined to study the transformation of organic matter during these advanced treatments. Low-molecular-weight matter was the predominant fraction in raw water, and it could not be removed effectively by ultrafiltration and biofiltration. The dominant species of disinfection by-product formation potential (DBPFP) in raw water were chloroform and monochloroacetic acid (MCAA), with average concentrations of 107.3 and 125.9 MUg/L, respectively. However, the formation potential of chloroform and MCAA decreased to 36.2 and 11.5 MUg/L after ultrafiltration. Similarly, biological pretreatment obtained high removal efficiency for DBPFP. The total THMFP decreased from 173.8 to 81.8 MUg/L, and the total HAAFP decreased from 211.9 to 84.2 MUg/L. Separate ozonation had an adverse effect on DBPFP, especially for chlorinated HAAFP. Numerous low-molecular-weight compounds such as aldehydes, ketones, and alcohols were generated during the ozonation, which have been proven to be important precursors of HAAs. However, the ozonation/biological activated carbon (BAC) combined process had a better removal efficiency for DBPFP. The total DBPFP decreased remarkably from 338.7 to 113.3 MUg/L after the O3/BAC process, far below the separated BAC of process B (189.1 MUg/L). PMID- 27180836 TI - Organic compounds present in airborne particles stimulate superoxide production and DNA fragmentation: role of NOX and xanthine oxidase in animal tissues. AB - Suspended particulate matter trigger the production of reactive oxygen species. However, most of the studies dealing with oxidative damage of airborne particles focus on the effects of individual compounds and not real mixtures. In order to study the enzymatic superoxide production resulting from the exposition to a complex mixture, we derived organic extracts from airborne particles collected daily in an urban area and exposed kidney, liver, and heart mammal tissues. After that, we measured DNA damage employing the comet assay. We observed that in every tissue, NADPH oxidase and xanthine oxidase were involved in O2 (-) production when they were exposed to the organic extracts, as the lucigenin's chemiluminescence decays when enzymes were inhibited. The same trend was observed with the percentage of cells with comets, since DNA damage was higher when they were exposed to same experimental conditions. Our data allow us to hypothesize that these enzymes play an important role in the oxidative stress produced by PAHs and that there is a mechanism involving them in the O2 (-)generation. PMID- 27180837 TI - Predicting seasonal fate of phenanthrene in aquatic environment with a Markov chain. AB - Phenanthrene (Phe) with carcinogenicity is ubiquitous in the environment, especially in aquatic environment; its toxicity is greater. To help determine toxicity risk and remediation strategies, this study predicted seasonal fate of Phe in aquatic environment. Candidate mechanisms including biodegradation, sorption, desorption, photodegradation, hydrolysis and volatility were studied; the results for experiments under simulated conditions for normal, wet and dry seasons in the Yinma River Basin indicated that biodegradation in sediment, sorption, desorption, and volatility were important pathways for elimination of Phe from aquatic environment and showed seasonal variations. A microcosm which was used to mimic sediment/water system was set up to illustrate seasonal distribution and transport of Phe. A Markov chain was applied to predict seasonal fate of Phe in air/water/sediment environment, the predicted results were perfectly agreed with results of microcosm experiments. Predicted results with a Markov chain suggested that volatility and biodegradation in sediment were main elimination pathways, and contributions of elimination pathways showed seasonal variations; Phe was eliminated from water and sediment to negligible levels over around 250 h in August and over 1000 h in May; in November, Phe was eliminated from water to a negligible level while about 31 % of Phe amount still remained in sediment over 1000 h. PMID- 27180838 TI - Eco-friendly drugs from the marine environment: spongeweed-synthesized silver nanoparticles are highly effective on Plasmodium falciparum and its vector Anopheles stephensi, with little non-target effects on predatory copepods. AB - Mosquitoes act as vectors of devastating pathogens and parasites, representing a key threat for millions of humans and animals worldwide. The control of mosquito borne diseases is facing a number of crucial challenges, including the emergence of artemisinin and chloroquine resistance in Plasmodium parasites, as well as the presence of mosquito vectors resistant to synthetic and microbial pesticides. Therefore, eco-friendly tools are urgently required. Here, a synergic approach relying to nanotechnologies and biological control strategies is proposed. The marine environment is an outstanding reservoir of bioactive natural products, which have many applications against pests, parasites, and pathogens. We proposed a novel method of seaweed-mediated synthesis of silver nanoparticles (AgNP) using the spongeweed Codium tomentosum, acting as a reducing and capping agent. AgNP were characterized by UV-Vis spectroscopy, Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and X-ray diffraction (XRD). In mosquitocidal assays, the 50 % lethal concentration (LC50) of C. tomentosum extract against Anopheles stephensi ranged from 255.1 (larva I) to 487.1 ppm (pupa). LC50 of C. tomentosum synthesized AgNP ranged from 18.1 (larva I) to 40.7 ppm (pupa). In laboratory, the predation efficiency of Mesocyclops aspericornis copepods against A. stephensi larvae was 81, 65, 17, and 9 % (I, II, III, and IV instar, respectively). In AgNP contaminated environment, predation was not affected; 83, 66, 19, and 11 % (I, II, III, and IV). The anti-plasmodial activity of C. tomentosum extract and spongeweed-synthesized AgNP was evaluated against CQ resistant (CQ-r) and CQ-sensitive (CQ-s) strains of Plasmodium falciparum. Fifty percent inhibitory concentration (IC50) of C. tomentosum were 51.34 MUg/ml (CQ-s) and 65.17 MUg/ml (CQ-r); C. tomentosum-synthesized AgNP achieved IC50 of 72.45 MUg/ml (CQ-s) and 76.08 MUg/ml (CQ-r). Furthermore, low doses of the AgNP inhibited the growth of Bacillus subtilis, Klebsiella pneumoniae, and Salmonella typhi, using the agar disk diffusion and minimum inhibitory concentration protocol. Overall, C. tomentosum metabolites and spongeweed-synthesized AgNP may be potential candidates to develop novel and effective tools in the fight against Plasmodium parasites and their mosquito vectors. The employ of ultra-low doses of nanomosquitocides in synergy with cyclopoid crustaceans seems a promising green route for effective mosquito control programs. PMID- 27180840 TI - On the causal links between health indicator, output, combustible renewables and waste consumption, rail transport, and CO2 emissions: the case of Tunisia. AB - This study employs the autoregressive distributed lag (ARDL) approach and Granger causality test to investigate the short- and long-run relationships between health indicator, real GDP, combustible renewables and waste consumption, rail transport, and carbon dioxide (CO2) emissions for the case of Tunisia, spanning the period of 1990-2011. The empirical findings suggest that the Fisher statistic of the Wald test confirm the existence of a long-run relationship between the variables. Moreover, the long-run estimated elasticities of the ARDL model provide that output and combustible renewables and waste consumption have a positive and statistically significant impact on health situation, while CO2 emissions and rail transport both contribute to the decrease of health indicator. Granger causality results affirm that, in the short-run, there is a unidirectional causality running from real GDP to health, a unidirectional causality from health to combustible renewables and waste consumption, and a unidirectional causality from all variables to CO2 emissions. In the long-run, all the computed error correction terms are significant and confirm the existence of long-run association among the variables. Our recommendations for the Tunisian policymakers are as follows: (i) exploiting wastes and renewable fuels can be a good strategy to eliminate pollution caused by emissions and subsequently improve health quality, (ii) the use of renewable energy as a main source for national rail transport is an effective strategy for public health, (iii) renewable energy investment projects are beneficial plans for the country as this contributes to the growth of its own economy and reduce energy dependence, and (iii) more renewable energy consumption leads not only to decrease pollution but also to stimulate health situation because of the increase of doctors and nurses numbers. PMID- 27180841 TI - Aluminum complexes containing salicylbenzoxazole ligands and their application in the ring-opening polymerization of rac-lactide and epsilon-caprolactone. AB - Two series of four-coordinate aluminum () and five-coordinate aluminum () complexes were successfully synthesized via the reactions between the corresponding salicylbenzoxazole ligands and 1 or 0.5 equivalents of AlMe3, respectively. The synthesized aluminum complexes were characterized by (1)H and (13)C NMR spectroscopy and elemental analysis. The solid-state structures of complexes and were determined using single crystal X-ray diffraction. Upon addition of 1 equivalent of benzyl alcohol, all complexes were efficient initiators for the ring-opening polymerization (ROP) of rac-lactide (rac-LA) and epsilon-caprolactone (epsilon-CL). The polymerizations were living with a good control over molecular weights and molecular weight distributions. Under immortal polymerization conditions, all four-coordinate aluminum complexes () exhibited a living polymerization with the obtained molecular weights proportional to the ratio of monomer/benzyl alcohol and the PDIs were narrow. Kinetic studies revealed that both rac-LA and epsilon-CL polymerizations mediated by all complexes were first-order in monomers. The effects of ligand structure and coordination geometry on the catalytic activity and stereoselectivity were discussed. A good isoselectivity control was achieved for the polymerizations mediated by complexes (Pm = 0.75), (Pm = 0.74), and (Pm = 0.74). PMID- 27180839 TI - Oxalate-assisted oxidative degradation of 4-chlorophenol in a bimetallic, zero valent iron-aluminum/air/water system. AB - The reaction of zero-valent iron and aluminum with oxygen produced reactive oxidants that can oxidize 4-chlorophenol (4-CP). However, oxidant yield without metal surface cleaning to dissolve the native oxide layer or in the absence of ligands was too low for practical applications. The addition of oxalate (ox) to dissolved oxygen-saturated solution of Fe(0)-Al(0) significantly increased oxidant yield because of the dissolution, pH buffer, and complexing characteristics of ox. Ox-enhanced reactive oxidant generation was affected by ox concentration and solution pH. The critical effect of ox dosing was confirmed with the reactive species of [Fe(II)(ox)0] and [Fe(II)(ox)2 (2-)]. Systematic studies on the effect of the initial and in situ solution pH revealed that 4-CP oxidation was controlled by the continuous release of dissolved Fe(2+) and Al(3+), their fate, and the activation mechanisms of O2 reduction. The degradation pathway of 4-CP in ox-enhanced Fe(0)-Al(0)/O2 may follow the 4 chlorocatechol pathway. The robustness of the ox-enhanced Al(0)-Fe(0)-O2 process was determined with one-time dosing of ox. Therefore, ox is an ideal additive to enhancing the Fe(0)-Al(0)/O2 system for the oxidative degradation of aqueous organic pollutants. PMID- 27180842 TI - Relevance of serum interleukin-33 and ST2 levels and the natural course of chronic hepatitis B virus infection. AB - BACKGROUND: Interleukin-33 (IL-33) and ST2 have been demonstrated to be associated with liver damage. However, their potential value in hepatitis B virus (HBV) infection remains unknown. This study was designed to investigate the change of serum IL-33 and ST2 levels in the natural course of chronic HBV infection. METHODS: A total of 120 patients with chronic hepatitis B (CHB), 20 chronic hepatitis B virus carriers in immunotolerant phase and 28 healthy controls were enrolled in this study. All patients with CHB were divided into four groups according to their serum ALT levels. The serum levels of IL-33 and ST2 of all participants were determined by enzyme-linked immunosorbent assay, and compared between each two out of those six groups. RESULTS: No significant differences were found in serum levels of IL-33 and ST2 between the group of CHB with ALT 1-2 upper limit of normal and the healthy controls (P = 0.354 for IL-33 and P = 0.815 for ST2). Other than that, there were significant differences when serum levels of IL-33 and ST2 were compared between any other two out of those six groups (P < 0.05, respectively). The overall correlation analysis indicated that changes of serum IL-33 and ST2 levels were positively associated with ALT levels in patients with chronic HBV infection (rs = 0.879, P < 0.001 for IL-33 and rs = 0.923, P < 0.001 for ST2). No significant differences were found when the serum levels of ALT, IL-33 and ST2 were compared between patients with HBeAg positive CHB and HBeAg-negative CHB. CONCLUSIONS: Our study revealed that the serum levels of IL-33 and ST2 varied in different courses of chronic hepatitis B virus infection. The serum levels of IL-33 and ST2 elevated as serum ALT levels increased in patients with CHB. They might indicate liver damage for patients with CHB, just like ALT. PMID- 27180866 TI - Ratiometric detection and imaging of endogenous hypochlorite in live cells and in vivo achieved by using an aggregation induced emission (AIE)-based nanoprobe. AB - An AIE-based fluorescent nanoprobe (MTPE-M) has been developed and used for ratiometric detection of hypochlorite with high selectivity and sensitivity. More importantly, its application in live cells and zebrafish for ratiometric imaging of endogenous ClO(-) has also been achieved. PMID- 27180868 TI - Influence of Dissolved O2 in Organic Solvents on CuOEP Supramolecular Self Assembly on Graphite. AB - The supramolecular self-assembly of copper(II) octaethylporphyrin (CuOEP) and octaethylporphyrin (H2OEP) on graphitic surfaces immersed in organic solvents (dichlorobenzene, dodecane) is studied using scanning tunneling microscopy (STM) and Raman spectroscopy. STM reveals that the self-assembled structure of CuOEP in 1,2-dichlorobenzene is significantly altered by dissolved oxygen within the solvent. Raman spectroscopy reveals that the presence of the oxygen alters the molecule-substrate interaction, which is attributed to the adsorption of oxygen on the Cu center of the CuOEP, which is facilitated by electron transfer from the graphitic surface. Such oxygen-induced changes are not observed for H2OEP, indicating that the metal center of CuOEP plays a critical role. When the solvent is dodecane, we find that solvation effects dominate. CuOEP adsorbed on graphitic surfaces provides a model system relevant to the study of the transport and activation of oxygen by enzymes and other complexes. PMID- 27180867 TI - Touch screens as a tool in patient care in the IBD outpatient clinic. AB - OBJECTIVE: We have introduced online touch screens in the waiting room for patients with ulcerative colitis (UC) or Crohn's disease (CD) for recording of symptoms before their consultation. This has made disease activity scores readily available to the physician in our newly established database, 'Gastrobio'. We wanted to validate the use of touch screens compared to paper questionnaires. MATERIAL AND METHODS: A total of 54 patients with UC and 74 patients with CD were included in the study. The UC patients filled out the Short Health Scale (SHS) and Simple Clinical Colitis Activity Index (SSCAI). The CD patients filled out the SHS and Harvey-Bradshaw Index (HBI). Paper questionnaires and touch screen versions were used in random order and comparison between the two modalities was made by Spearman correlation test, Bland-Altman plots, and Kappa-statistics. RESULTS: Among the 128 patients, the two SHS scores (SHS touch versus SHS paper) were found to be highly correlated (Spearman correlation; 0.92 for UC and 0.92 for CD). Also, on average, Bland-Altman plots demonstrated a difference close to zero between the two modalities. Agreement between paper version and touch screen version of SCCAI and HBI scores was also high (Kappa-statistics; 78% raw and 98% weighted for SCCAI; 65% raw and 97% weighted for HBI). CONCLUSIONS: It is feasible to introduce touch screens in the outpatient clinic and to have patients record their symptoms before the consultation. However, the study may not be representative for elderly patients. PMID- 27180869 TI - Antibacterial properties and mechanisms of gold-silver nanocages. AB - Despite the number of antibiotics used in routine clinical practice, bacterial infections continue to be one of the most important challenges faced in humans. The main concerns arise from the continuing emergence of antibiotic-resistant bacteria and the difficulties faced with the pharmaceutical development of new antibiotics. Thus, advancements in the avenue of novel antibacterial agents are essential. In this study, gold (Au) was combined with silver (Ag), a well-known antibacterial material, to form silver nanoparticles producing a gold-silver alloy structure with hollow interiors and porous walls (gold-silver nanocage). This novel material was promising in antibacterial applications due to its better biocompatibility than Ag nanoparticles, potential in photothermal effects and drug delivery ability. The gold-silver nanocage was then tested for its antibacterial properties and the mechanism involved leading to its antibacterial properties. This study confirms that this novel gold-silver nanocage has broad spectrum antibacterial properties exerting its effects through the destruction of the cell membrane, production of reactive oxygen species (ROS) and induction of cell apoptosis. Therefore, we introduce a novel gold-silver nanocage that serves as a potential nanocarrier for the future delivery of antibiotics. PMID- 27180870 TI - Overproduction and identification of butyrolactones SCB1-8 in the antibiotic production superhost Streptomyces M1152. AB - Gamma-butyrolactones (GBLs) are signalling molecules that control antibiotic production in Streptomyces bacteria. The genetically engineered strain S. coelicolor M1152 was found to overproduce GBLs SCB1-3 as well as five novel GBLs named SCB4-8. Incorporation experiments using isotopically-labelled precursors confirmed the chemical structures of SCB1-3 and established those of SCB4-8. PMID- 27180871 TI - A new family of 1D, 2D and 3D frameworks aggregated from Ni5, Ni4 and Ni7 building units: synthesis, structure, and magnetism. AB - Three new Ni(ii)-clusters based on a Y-shaped ligand (biphenyl-3,4',5 tricarboxylate, H3BPT), [Ni5(HBPT)4(OH)2(H2O)12]n (), [Ni4(BPT)2(OH)2(H2O)6]n.4nH2O (), and [Ni7(BPT)2(1,4-bib)2(OH)6(HCO2)2]n.3nH2O () (1,4-bib = 1,4-bi(1H-imidazol-1-yl)benzene), have been synthesized under solvothermal conditions. They were studied by infrared spectroscopy (IR), single crystal X-ray diffraction, thermogravimetric analysis (TGA), and magnetochemistry. The complexes contain low nuclear Ni-clusters as building units (BUs). Structurally, in , the cluster BUs of [Ni5(MU3-OH)2](8+) can be viewed as two reverse triangles sharing a common vertex, which are connected by the partially deprotonated MU2-eta(1):eta(1)-HBPT(2-) forming 1D chains. The BUs of [Ni4(MU3-OH)2](6+) clusters in can be considered as two reverse triangles sharing a common edge and extended by deprotonated MU6-eta(1):eta(1):eta(1):eta(1):eta(2) BPT(3-) constructing a 2D framework. The 3D framework of complex consists of a [Ni7(MU3-OH)4(R-COO)7(HCO2)3] cluster BUs with fully deprotonated MU5 eta(1):eta(1):eta(1):eta(1):eta(1):eta(1)-BPT(3-) and 1,4-bib ligands. In addition, TGA reveals that the complexes are stable in the range of 293-548 K. Magnetostructural analyses indicate ferromagnetic coupling of J1 = 1.85(3) and J2 = 2.25(4) cm(-1) in and J = 5.76(6) cm(-1) in , whereas magnetic parameters J1 = 2.64(3), J2 = -23.22(19) and J3 = 12.02(5) cm(-1) indicate an alternating magnetic chain (AF/F) in . PMID- 27180872 TI - Room-temperature and gram-scale synthesis of CsPbX3 (X = Cl, Br, I) perovskite nanocrystals with 50-85% photoluminescence quantum yields. AB - All inorganic CsPbX3 (X = Cl, Br, I) perovskite nanocrystals (PNCs) with 50-85% photoluminescence quantum yields and tunable emission in the range of 440-682 nm have been successfully synthesized at room temperature in open air. This facile strategy enables us to prepare gram-scale CsPbBr3 NCs with a PLQY approaching 80%. PMID- 27180874 TI - Non-volatile transistor memory devices using charge storage cross-linked core shell nanoparticles. AB - Solution processable cross-linked core-shell poly[poly(ethylene glycol)methylether methacrylate]-block-poly(2,5-dibromo-3-vinylthiophene) (poly(PEGMA)m-b-poly(DB3VT)n) nanoparticles are firstly explored as charge storage materials for transistor-type memory devices owing to their efficient and controllable ability in electric charge transfer and trapping. PMID- 27180873 TI - Ultrafast dynamics of quasiparticles and coherent acoustic phonons in slightly underdoped (BaK)Fe2As2. AB - We have utilized ultrafast optical spectroscopy to study carrier dynamics in slightly underdoped (BaK)Fe2As2 crystals without magnetic transition. The photoelastic signals due to coherent acoustic phonons have been quantitatively investigated. According to our temperature-dependent results, we found that the relaxation component of superconducting quasiparticles persisted from the superconducting state up to at least 70 K in the normal state. Our findings suggest that the pseudogaplike feature in the normal state is possibly the precursor of superconductivity. We also highlight that the pseudogap feature of K doped BaFe2As2 is different from that of other iron-based superconductors, including Co-doped or P-doped BaFe2As2. PMID- 27180875 TI - Secondary plasma formation after single pulse laser ablation underwater and its advantages for laser induced breakdown spectroscopy (LIBS). AB - In this work we present studies of spatial and temporal plasma evolution after single pulse ablation of an aluminium target in water. The laser ablation was performed using 20 ns long pulses emitted at 1064 nm. The plasma characterization was performed by fast photography, the Schlieren technique, shadowgraphy and optical emission spectroscopy. The experimental results indicate the existence of two distinct plasma stages: the first stage has a duration of approximately 500 ns from the laser pulse, and is followed by a new plasma growth starting from the crater center. The secondary plasma slowly evolves inside the growing vapor bubble, and its optical emission lasts over several tens of microseconds. Later, the hot glowing particles, trapped inside the vapor cavity, were detected during the whole cycle of the bubble, where the first collapse occurs after 475 MUs from the laser pulse. Differences in the plasma properties during the two evolution phases are discussed, with an accent on the optical emission since its detection is of primary importance for LIBS. Here we demonstrate that the LIBS signal quality in single pulse excitation underwater can be greatly enhanced by detecting only the secondary plasma emission, and also by applying long acquisition gates (in the order of 10-100 MUs). The presented results are of great importance for LIBS measurements inside a liquid environment, since they prove that a good analytical signal can be obtained by using nanosecond pulses from a single commercial laser source and by employing cost effective, not gated detectors. PMID- 27180876 TI - A novel nucleoside hydrolase from Lactobacillus buchneri LBK78 catalyzing hydrolysis of 2'-O-methylribonucleosides. AB - 2'-O-Methylribonucleosides (2'-OMe-NRs) are promising raw materials for nucleic acid drugs because of their high thermal stability and nuclease tolerance. In the course of microbial screening for metabolic activity toward 2'-OMe-NRs, Lactobacillus buchneri LBK78 was found to decompose 2'-O-methyluridine (2'-OMe UR). The enzyme responsible was partially purified from L. buchneri LBK78 cells by a four-step purification procedure, and identified as a novel nucleoside hydrolase. This enzyme, LbNH, belongs to the nucleoside hydrolase superfamily, and formed a homotetrameric structure composed of subunits with a molecular mass around 34 kDa. LbNH hydrolyzed 2'-OMe-UR to 2'-O-methylribose and uracil, and the kinetic constants were Km of 0.040 mM, kcat of 0.49 s(-1), and kcat/Km of 12 mM( 1) s(-1). In a substrate specificity analysis, LbNH preferred ribonucleosides and 2'-OMe-NRs as its hydrolytic substrates, but reacted weakly with 2' deoxyribonucleosides. In a phylogenetic analysis, LbNH showed a close relationship with purine-specific nucleoside hydrolases from trypanosomes. PMID- 27180877 TI - Stress and coping in parents of newly born twins. AB - OBJECTIVE: Research indicates that parents of twins have poorer psychosocial outcomes than parents of singletons. Parents who have conceived using assisted reproductive technology (ART) have been found to be at higher risk of negative psychosocial outcomes compared to parents who have conceived spontaneously. The current study aimed to model the factors associated with parenting stress of newly-born twins, using the Transactional Model of Stress. METHODS: Data were collected using a cross-sectional survey design with participants identified from delivery records across Northern Ireland. Mothers and fathers (n = 104) of twins aged between 1 and 12 months old returned a questionnaire pack containing the Parenting Stress Index, Impact on the Family Scale-Financial Burden, Coping Orientation to Problems Experienced - Brief Version, Multidimensional Scale of Perceived Social Support, General Health Questionnaire and a demographic questionnaire. RESULTS: There were no differences on psychological outcomes between parents who had conceived via ART and those who conceived spontaneously. Regression analyses found that social interaction and support is an important variable in terms of the psychological outcomes experienced by parents of twins. CONCLUSION: Parents of newly-born twins regardless of the mode of conception should be considered an at risk group for parental distress. Support groups such as the Twins and Multiple Births Association could be important in providing that crucial social interaction and support that seems to be important in the emotional well-being of parents of twins. PMID- 27180878 TI - Genotoxicity and cytotoxicity of oxindole alkaloids from Uncaria tomentosa (cat's claw): Chemotype relevance. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Uncaria tomentosa (Willdenow ex Roemer & Schultes) DC. (Rubiaceae) or cat's claw is a climber vine from the South American rainforest used in folk medicine for cancer treatment. Its antitumor activity has been mostly ascribed to pentacyclic oxindole alkaloids (POA) from stem bark and leaves while the activity of tetracyclic oxindole alkaloids (TOA) remains unknown. In recent times, the occurrence of three chemotypes based on its oxindole alkaloid profile was noticed in U. tomentosa, namely, chemotype I (POA cis D/E ring junction); chemotype II (POA trans D/E ring junction) or chemotype III (TOA). Consequently, the relationship between the chemotype and cytotoxic and genotoxic activities deserves attention. AIM OF THE STUDY: To evaluate the influence of cat's claw chemotypes on genotoxicity and cytotoxicity against non malignant and malignant human cell line models. MATERIAL AND METHODS: Four authentic stem bark cat's claw samples (SI-SIV) and two leaf samples (LII and LIII) were analyzed by HPLC-PDA, properly extracted and fractioned by ion exchange to obtain oxindole alkaloid purified fractions (OAPFs). The freeze-dried fractions were assayed for genotoxicity and cytotoxicity against human leukocytes (non malignant cell line) by the micronuclei frequency method and the alkaline comet DNA assay, and the trypan blue method, respectively. Moreover, the cytotoxicity of each OAPF was evaluated against a human bladder cancer cell line (T24) and human glioblastoma cell line (U-251-MG) by MTT method (malignant cell lines). Additionally, the isomerization of oxindole alkaloids throughout the course of cell incubation was monitored by HPLC-PDA. RESULTS: Based on HPLC-PDA analyses, sample SI was characterized as chemotype I, while samples SII and LII were characterized as chemotype II, and samples SIII, SIV and LIII as chemotype III. The chemotypes showed comparable cytotoxic activity toward malignant cell lines (T24 and U-251-MG) unlike human leukocytes (non malignant cell line), where this activity was clearly distinct. Chemotype II (POA trans D/E ring junction) showed a higher selectivity index (SI) against malignant cells (SI=1.11-3.04) than chemotype I (SI=0.10-0.19) and III (SI=0.21-0.57). No important genotoxic potential was found by micronuclei frequency and alkaline comet DNA assays. Despite the isomerization of oxindole alkaloids during the cell incubation, the chemotype of the cat's claw samples remained unchanged. CONCLUSION: Cat's claw chemotypes showed different selectivity against human malignant cells, so that the correct identification of each chemotype seems to be important to better understand its antitumor potential. PMID- 27180879 TI - Eupafolin ameliorates COX-2 expression and PGE2 production in particulate pollutants-exposed human keratinocytes through ROS/MAPKs pathways. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Eupafolin is a major bioactive compound derived from the methanolic extract of the medicinal herb Phyla nodiflora, which has been used in traditional Chinese medicine to treat various inflammatory diseases. Recently, particulate air pollutants have been shown to induce inflammation of the skin. In this study, we seek to determine whether eupafolin can inhibit the production of inflammatory mediators in a human skin keratinocyte cell line exposed to particulate air pollutants (particulate matter, PM), and determine the molecular mechanisms involved. MATERIALS AND METHODS: Human keratinocyte HaCaT cells were treated with PM in the presence or absence of eupafolin. Cyclooxygenase-2 (COX-2) protein and gene expression levels were determined by Western blotting, RT-PCR and luciferase activity assay. Prostaglandin E2 (PGE2) production was evaluated by the enzyme immunoassay method. Generation of intracellular reactive oxygen species (ROS) was measured by the dichlorofluorescin (DCFH) oxidation assay, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity was determined by a chemiluminescence assay. For in vivo studies, COX-2 expression in the skin of BALB/c nude mice was analyzed by immunohistochemistry. RESULTS: Eupafolin inhibited PM-induced COX-2 protein and gene expression and PGE2 production in HaCaT cells. In addition, eupafolin suppressed PM-induced intracellular ROS generation, NADPH oxidase activity, MAPK (ERK, JNK and p38) activation and NK-kappaB activation. In vivo studies showed that topical treatment with eupafolin inhibited COX-2 expression in the epidermal keratinocytes of PM-treated mice. CONCLUSIONS: Eupafolin exerts anti-inflammatory and antioxidant effects on skin keratinocytes exposed to particulate air pollutants, and may have potential use in the treatment or prevention of air pollutant-induced inflammatory skin diseases in the future. PMID- 27180880 TI - Iridoid glycosides from the flowers of Gentiana macrophylla Pall. ameliorate collagen-induced arthritis in rats. AB - BACKGROUND: The flowers of Gentiana macrophylla have been usually applied to cure the joint inflammation and rheumatoid arthritis in Traditional Chinese Medicine. HYPOTHESIS/PURPOSE: This work aimed to investigate the anti-rheumatoid arthritic effect and possible mechanism of iridoid glycosides from G. macrophylla (GMI) using an animal model of collagen-induced rheumatoid arthritis (CIA) in rats. STUDY DESIGN: All rats were randomly divided into five groups: normal control, CIA, dexamethasone, 15mg/kg and 30mg/kg GMI. METHODS: CIA was induced (day 0) in male Sprague-Dawley rats by intradermal injection of complete Bovine CII at the base of the tail. Dexamethasone was chosen as the positive drug. The administration of different drugs started from day 1 and continued for 28 days. Paw swelling, arthritis score and histopathological changes were examined to assess the severity of arthritis. In addition, the serum levels of tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expressions in joint synovial tissues were detected. RESULTS: GMI reduced paw edema, arthritis scores and the index of spleen and thymus from day 7 to 21 after CIA compared with those in the CIA group. Our data also demonstrated that GMI inhibited pro-inflammatory cytokines such as TNF-alpha, IL-1beta and IL-6, regulated the expression of iNOS and COX-2 compared with those in the CIA group. We also obtained four major components from GMI, identified as loganic acid, swertamarin, gentiopicroside and sweroside, and the contents of them were also calculated respectively. CONCLUSION: Taken together, our results shed light on the therapeutic efficacy of GMI in rats rheumatoid arthritis model by reducing the levels of IL-1beta, IL-6 and TNF-alpha in serum as well as down-regulating the levels of iNOS and COX-2. Therefore, GMI may be an effective therapy for the treatment of rheumatoid arthritis. PMID- 27180881 TI - The effects of Arnebia euchroma ointment on second-degree burn wounds: a randomized clinical trial. AB - ETHNOBOTANICAL RELEVANCE: Burn injuries can cause detrimental long-term consequences and call for immediate management. Avicenna's Canon of Medicine, describing the use of Abu-Khalsa (Arnebia euchroma) (AE) as being effective for burn healing. The purpose of this study was to evaluate the healing effects of AE ointment (AEO) on patients with a second-degree burn wound and compare its results with silver sulfadiazine cream (SSD). MATERIALS AND METHODS: In this prospective, single-blind clinical trial, 45 patients with similar types of second-degree burns at two different sites of the body were randomly assigned to the two treatment groups. One burn wound site of the patient was treated with SSD and another similar burn wound site with AEO once a day until complete healing was achieved. Wound size and percentage of wound healing were evaluated at 15 days. Satisfaction, clinical adverse events such as pain, burning, warming, erythema, edema, infection, inflammation, and general wound area were assessed on a visual analogue scales, and 6-point scales. RESULTS: The healing time was significantly shorter in the site treated with AEO than SSD (13.9+/-5.3 vs. 17.5+/-6.9 days, respectively). The severity of pain and burning were reduced in the AEO site compared with SSD site at the time of dressing change, while the warming score was significantly higher in the AEO wound area. Side-effects were lower in the site treated with AEO. CONCLUSION: In this clinical study, we demonstrated that AEO has benefits over SSD in the treatment of second-degree burn wounds and wound healing and is a viable medication for the management of second-degree burns. PMID- 27180884 TI - Evidence against an etiological role of lactobacilli and diphtheroids in dysuria and frequency in females. PMID- 27180882 TI - Elevated endocan concentration is associated with coronary slow flow. AB - We sought to assess whether serum endocan concentration is correlated with coronary slow flow (CSF). We measured serum endocan concentration in 93 patients with CSF and in 206 controls. Serum endocan concentration was measured by enzyme linked immunosorbent assay (ELISA). The presence of CSF was assessed by thrombolysis in myocardial infarction (TIMI) frame count (TFC) method. We demonstrated that serum endocan concentration is significantly higher in CSF patients (n = 93) than that in controls (n = 206) (1.03 [range 0.63-1.33] vs. 0.80 [range 0.52-1.09] ng/mL, p = 0.002). Multivariate logistic regression analysis revealed that serum endocan concentration was independently associated with the presence of CSF (odds ratio 1.774, 95% confidence interval 1.064-2.958; p = 0.028). Serum endocan concentration was positively correlated with mean-TFC in CSF patients (r = 0.289, p = 0.005). These results revealed that endocan might be a useful biomarker for predicting the presence and severity of CSF. Therapeutic interventions by down-regulating endocan to delay the progressive process of CSF warrants further investigations. PMID- 27180883 TI - Effects of ADMA on gene expression and metabolism in serum-starved LoVo cells. AB - Serum starvation is a typical way for inducing tumor cell apoptosis and stress. Asymmetric dimethylarginine (ADMA) is an endogenous metabolite. Our previous study reveals the plasma ADMA level is elevated in colon cancer patients, which can attenuate serum starvation-induced apoptosis in LoVo cells. In current study, we evaluated the effects of ADMA on gene expression and metabolism in serum starved LoVo cells with gene microarray and metabolomic approaches. Our results indicated that 96 h serum starvation induced comprehensive alterations at transcriptional level, and most of them were restored by ADMA. The main signaling pathways induced by serum starvation included cancers-related pathways, pathways in cell death, apoptosis, and cell cycle etc. Meanwhile, the metabolomic data showed serum-starved cells were clearly separated with control cells, but not with ADMA-treated cells in PCA model. The identified differential metabolites indicated serum starvation significantly suppressed TCA cycle, altered glucose and fatty acids metabolism, as well as nucleic acids metabolism. However, very few differential metabolites were identified between ADMA and serum-starved cells. In summary, our current results indicated serum starvation profoundly altered the gene expression and metabolism of LoVo cells, whereas ADMA could restore most of the changes at transcriptional level, but not at metabolic level. PMID- 27180885 TI - Bupropion therapy during pregnancy: the drug and its major metabolites in umbilical cord plasma and amniotic fluid. AB - BACKGROUND: Bupropion is used for treatment of depression during pregnancy. However, its use as a smoking cessation aid for pregnant women is currently under evaluation. OBJECTIVE: The aim of this opportunistic study was to investigate the transfer of bupropion and its major pharmacologically active metabolites, hydroxybupropion and threohydrobupropion, across the placenta in vivo. In addition, the concentrations of the drug and its metabolites were determined in the amniotic fluid. STUDY DESIGN: The following samples were collected at deliveries from 22 women taking bupropion: maternal blood (n = 22), umbilical cord venous blood (n = 22), and amniotic fluid (n = 9). The concentrations of the drug and its metabolites in blood plasma and amniotic fluid were determined by means of liquid chromatography-mass spectrometry. Placental passage was calculated as a ratio of umbilical cord venous plasma to maternal plasma concentrations. RESULTS: The levels of hydroxybupropion and threohydrobupropion in umbilical cord venous plasma were invariably lower than their corresponding concentrations in maternal plasma. The concentrations of bupropion in umbilical cord plasma were lower than in maternal plasma in the majority of the maternal cord blood pairs. The median values of the umbilical cord venous plasma to maternal plasma ratios were: bupropion, 0.53 (interquartile range 0.35, n = 18), hydroxybupropion, 0.21 (interquartile range 0.12, n = 18), and threohydrobupropion, 0.61 (interquartile range 0.11, n = 21). In umbilical cord venous plasma, the median concentration of bupropion was 5.3 ng/mL; hydroxybupropion, 103.6 ng/mL; and threohydrobupropion, 59.6 ng/mL. Bupropion and its metabolites were detectable in the amniotic fluid but the concentrations of threohydrobupropion were higher than those in the corresponding umbilical cord venous plasma. CONCLUSION: Bupropion and its active metabolites cross the placenta to the fetal circulation. The concentrations of hydroxybupropion and threohydrobupropion in umbilical cord venous plasma were higher than bupropion concentrations suggesting a higher fetal exposure to the metabolites than the parent drug. The higher levels of threohydrobupropion in the amniotic fluid than those in umbilical cord venous plasma suggest that enzymes involved in the metabolism of bupropion to threohydrobupropion are most likely active in the fetus. The biological consequences of fetal exposure to maternally administered bupropion and/or its active metabolites via placental transfer and recirculation of the amniotic fluid are yet to be determined. PMID- 27180886 TI - A prospective assessment of pelvic infection risk following same-day sexually transmitted infection testing and levonorgestrel intrauterine system placement. AB - BACKGROUND: Misperceptions persist that intrauterine device placement is related to pelvic infections and Chlamydia and gonorrhea testing results are needed prior to placement. OBJECTIVE: We sought to evaluate the relationship of Chlamydia and gonorrhea screening to pelvic infection for up to 2 years following placement of the levonorgestrel 52-mg intrauterine system. STUDY DESIGN: A total of 1751 nulliparous and multiparous females 16 to 45 years old enrolled in a multicenter trial designed to evaluate the efficacy and safety of a new levonorgestrel intrauterine system for up to 7 years. Participants had Chlamydia screening at study entry and yearly if they were age <=25 years. Women also had baseline gonorrhea screening if testing had not been performed since starting their current sexual relationship. Those who changed sexual partners during the trial had repeated Chlamydia and gonorrhea testing. Intrauterine system insertion could occur on the same day as screening. Participants did not receive prophylactic antibiotics for intrauterine system placement. Investigators performed pelvic examinations after 12 and 24 months and when clinically indicated during visits at 3, 6, and 18 months after placement and unscheduled visits. Pelvic infection included any clinical diagnosis of pelvic inflammatory disease or endometritis. RESULTS: Most participants (n = 1364, 79.6%) did not have sexually transmitted infection test results available prior to intrauterine system placement. In all, 29 (1.7%) participants had positive baseline testing for a sexually transmitted infection (Chlamydia, n = 25; gonorrhea, n = 3; both, n = 1); 6 of these participants had known results (all with Chlamydia infection) prior to intrauterine system placement and received treatment before enrollment. The 23 participants whose results were not known at the time of intrauterine system placement received treatment without intrauterine system removal and none developed pelvic infection. The incidence of positive Chlamydia testing was similar among those with and without known test results at the time of intrauterine system placement (1.9% vs 1.5%, respectively, P = .6). Nine (0.5%) participants had a diagnosis of pelvic infection over 2 years after placement, all of whom had negative Chlamydia screening on the day of or within 1 month after intrauterine system placement. Infections were diagnosed in 3 participants within 7 days, 1 at 39 days, and 5 at >=6 months. Seven participants received outpatient antibiotic treatment and 2 (diagnoses between 6-12 months after placement) received inpatient treatment. Two (0.1%) participants had intrauterine system removal related to infection (at 6 days and at 7 months after placement), both of whom only required outpatient treatment. CONCLUSION: Conducting Chlamydia and gonorrhea testing on the same day as intrauterine system placement is associated with a low risk of pelvic infection (0.2%). Over the first 2 years of intrauterine system use, infections are infrequent and not temporally related to intrauterine system placement. Pelvic infection can be successfully treated in most women with outpatient antibiotics and typically does not require intrauterine system removal. Women without clinical evidence of active infection can have intrauterine system placement and sexually transmitted infection screening, if indicated, on the same day. PMID- 27180887 TI - Two-dimensional liquid chromatography coupled to tandem mass spectrometry for vitamin D metabolite profiling including the C3-epimer-25-monohydroxyvitamin D3. AB - A method based on automated on-line solid phase extraction coupled to two dimensional liquid chromatography with tandem mass spectrometry detection (SPE 2DLC-MS/MS) is here reported for vitamin D metabolite profiling in human serum with absolute quantitation. Two-dimensional LC was configured with two complementary analytical columns, pentafluorophenyl (PFP) and C18 phases, for determination of 25 hydroxyvitamin D3 epimers and the resting bioactive metabolites of vitamin D (D3 and D2)-25-hydroxyvitamin D2, 1,25-dihydroxyvitamin D3, 1,25-dihydroxyvitamin D2 and 24,25-dihydroxyvitamin D3. Quantitative determination was supported on the use of a stable isotopic labelled internal standard for each analyte and the resulting method was validated by analysis of a standard reference material certified by the National Institute of Standards & Technology (NIST-972a) and 5 samples provided by the vitamin D External Quality Assurance Scheme (DEQAS). The limits of detection were between 9 and 90pg/mL for the eight analytes, and precision, expressed as relative standard deviation, was lower than 11.6%. Two-dimensional LC has shown to be the key to discriminate between 25 hydroxyvitamin D3 epimers in a quantitative analysis also involving dihydroxyvitamin D metabolites. PMID- 27180889 TI - Atrial Fibrillation-Mediated Upregulation of miR-30d Regulates Myocardial Electrical Remodeling of the G-Protein-Gated K(+) Channel, IK.ACh. AB - BACKGROUND: Atrial fibrillation (AF) begets AF in part due to atrial remodeling, the molecular mechanisms of which have not been completely elucidated. This study was conducted to identify microRNA(s) responsible for electrical remodeling in AF. METHODS AND RESULTS: The expression profiles of 1205 microRNAs, in cardiomyocytes from patients with persistent AF and from age-, gender-, and cardiac function-matched control patients with normal sinus rhythm, were examined by use of a microRNA microarray platform. Thirty-nine microRNAs differentially expressed in AF patients' atria were identified, including miR-30d, as a candidate responsible for ion channel remodeling by in silico analysis. MiR-30d was significantly upregulated in cardiomyocytes from AF patients, whereas the mRNA and protein levels ofCACNA1C/Cav1.2 andKCNJ3/Kir3.1, postulated targets of miR-30d, were markedly reduced.KCNJ3/Kir3.1 expression was downregulated by transfection of the miR-30 precursor, concomitant with a reduction of the acetylcholine-sensitive inward-rectifier K(+)current (IK.ACh).KCNJ3/Kir3.1 (but notCACNA1C/Cav1.2) expression was enhanced by the knockdown of miR-30d. The Ca(2+)ionophore, A23187, induced a dose-dependent upregulation of miR-30d, followed by the suppression ofKCNJ3mRNA expression. Blockade of protein kinase C signaling blunted the [Ca(2+)]i-dependent downregulation of Kir3.1 via miR-30d. CONCLUSIONS: The downward remodeling ofIK.AChis attributed, at least in part, to deranged Ca(2+)handling, leading to the upregulation of miR-30d in human AF, revealing a novel post-transcriptional regulation ofIK.ACh. (Circ J 2016; 80: 1346-1355). PMID- 27180888 TI - Doping control analysis of 46 polar drugs in horse plasma and urine using a 'dilute-and-shoot' ultra high performance liquid chromatography-high resolution mass spectrometry approach. AB - The high sensitivity of ultra high performance liquid chromatography coupled with high resolution mass spectrometry (UHPLC-HRMS) allows the identification of many prohibited substances without pre-concentration, leading to the development of simple and fast 'dilute-and-shoot' methods for doping control for human and equine sports. While the detection of polar drugs in plasma and urine is difficult using liquid-liquid or solid-phase extraction as these substances are poorly extracted, the 'dilute-and-shoot' approach is plausible. This paper describes a 'dilute-and-shoot' UHPLC-HRMS screening method to detect 46 polar drugs in equine urine and plasma, including some angiotensin-converting enzyme (ACE) inhibitors, sympathomimetics, anti-epileptics, hemostatics, the new doping agent 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR), as well as two threshold substances, namely dimethyl sulfoxide and theobromine. For plasma, the sample (200MUL) was protein precipitated using trichloroacetic acid, and the resulting supernatant was diluted using Buffer A with an overall dilution factor of 3. For urine, the sample (20MUL) was simply diluted 50-fold with Buffer A. The diluted plasma or urine sample was then analysed using a UHPLC-HRMS system in full-scan ESI mode. The assay was validated for qualitative identification purpose. This straightforward and reliable approach carried out in combination with other screening procedures has increased the efficiency of doping control analysis in the laboratory. Moreover, since the UHPLC-HRMS data were acquired in full-scan mode, the method could theoretically accommodate an unlimited number of existing and new doping agents, and would allow a retrospectively search for drugs that have not been targeted at the time of analysis. PMID- 27180890 TI - Efficacy and Safety of a Novel Endothelin Receptor Antagonist, Macitentan, in Japanese Patients With Pulmonary Arterial Hypertension. AB - BACKGROUND: Macitentan is a novel, dual endothelin receptor antagonist with sustained receptor binding, used for the long-term treatment of pulmonary arterial hypertension (PAH). In the present study, we assessed the efficacy and safety of macitentan in Japanese patients with PAH. METHODS AND RESULTS: Macitentan was administered at a once-daily dose of 10 mg in 30 patients. The primary endpoint was change in pulmonary vascular resistance (PVR) from baseline to week 24. Change to week 24 in the other hemodynamic parameters, 6-min walk distance (6MWD), World Health Organization (WHO) functional class, and plasmaN terminal pro-brain natriuretic peptide (NT-pro-BNP), as well as time to clinical deterioration up to week 52 were also assessed as secondary endpoints. In the 28 patients on per-protocol analysis, PVR decreased from 667+/-293 to 417+/-214 dyn.sec.cm(-5)(P<0.0001). 6MWD increased from 427+/-128 to 494+/-116 m (P<0.0001). WHO functional class improved in 13 patients (46.4%) and was maintained in 15 patients (53.6%), and NT-pro-BNP was reduced by 18% (P<0.0001). The favorable treatment effect on PVR was apparent regardless of concomitant therapy for PAH. CONCLUSIONS: Macitentan was efficacious and well tolerated and improved the hemodynamic parameters, exercise capacity, symptoms, and clinical biomarkers in Japanese PAH patients. Macitentan can be a valuable therapeutic option for Japanese patients with PAH. ( TRIAL REGISTRATION: JAPIC Clinical Trials Information [JapicCTI-121986].) (Circ J 2016; 80: 1478-1483). PMID- 27180891 TI - Catecholaminergic Polymorphic Ventricular Tachycardia. AB - Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited cardiac arrhythmia disorder that is characterized by emotion- and exercise induced polymorphic ventricular arrhythmias and may lead to sudden cardiac death (SCD). CPVT plays an important role in SCD in the young and therefore recognition and adequate treatment of the disease are of vital importance. In the past years tremendous improvements have been made in the diagnostic methods and treatment of the disease. In this review, we summarize the clinical characteristics, genetics, and diagnostic and therapeutic strategies of CPVT and describe the most recent advances and some of the current challenges. (Circ J 2016; 80: 1285-1291). PMID- 27180892 TI - Mechanical Cardiopulmonary Resuscitation In and On the Way to the Cardiac Catheterization Laboratory. AB - Cardiac arrest, though not common during coronary angiography, is increasingly occurring in the catheterization laboratory because of the expanding complexity of percutaneous interventions (PCI) and the patient population being treated. Manual chest compression in the cath lab is not easily performed, often interrupted, and can result in the provider experiencing excessive radiation exposure. Mechanical cardiopulmonary resuscitation (CPR) provides unique advantages over manual performance of chest compression for treating cardiac arrest in the cardiac cath lab. Such advantages include the potential for uninterrupted chest compressions, less radiation exposure, better quality chest compressions, and less crowded conditions around the catheterization table, allowing more attention to ongoing PCI efforts during CPR. Out-of-hospital cardiac arrest patients not responding to standard ACLS therapy can be transported to the hospital while mechanical CPR is being performed to provide safe and continuous chest compressions en route. Once at the hospital, advanced circulatory support can be instituted during ongoing mechanical CPR. This article summarizes the epidemiology, pathophysiology and nature of cardiac arrest in the cardiac cath lab and discusses the mechanics of CPR and defibrillation in that setting. It also reviews the various types of mechanical CPR and their potential roles in and on the way to the laboratory. (Circ J 2016; 80: 1292-1299). PMID- 27180893 TI - Phylodynamics of the major HIV-1 CRF02_AG African lineages and its global dissemination. AB - The HIV-1 CRF02_AG clade is the most prevalent HIV variant in West and West Central Africa and its detection outside Africa is increasingly common. Little is known, however, about the number and phylodynamics of major CRF02_AG lineages circulating worldwide. To this end, a total of 3170 HIV-1 CRF02_AG-like pol sequences isolated around the world, over a period of 25years (1989 to 2013), were analyzed using Maximum Likelihood and Bayesian coalescent-based methods. Our results suggest that most of the current CRF02_AG diversity comes from the dissemination of a few founder strains out of Central Africa into West Africa and Cameroon between the late 1960s and the middle 1980s. The CRF02_AG strain introduced into West Africa established a large regional epidemic with low phylogeographic structure. This strain was also successfully disseminated out of the West African region and originated at least three large secondary outbreaks in Cameroon at around the late 1970s, in the former Soviet Union (FSU) countries at around the late 1990s, and in Bulgaria/Germany at around the early 2000s. The CRF02_AG African lineages introduced into Cameroon remained mostly restricted to this country and its neighbors. Demographic reconstructions indicate that major CRF02_AG clades circulating in Africa exhibited a decline in growth rate since the middle 1980s/1990s, whereas CRF02_AG clades in Europe and the FSU countries continue to grow exponentially until the middle to late 2000s. Substantial differences in the median estimated growth rate of the same CRF02_AG clade circulating in different regions (0.63-2.00year-1), and of different CRF02_AG clades circulating in the same country (0.41-0.75year-1) were observed. Thus, the cause of the epidemic outcome of the different HIV-1 CRF02_AG lineages is probably multifactorial. PMID- 27180894 TI - Worldwide population genetic analysis and natural selection in the Plasmodium vivax Generative Cell Specific 1 (PvGCS1) as a transmission-blocking vaccine candidate. AB - GENERATIVE CELL SPECIFIC 1 (GCS1) is one of the Transmission Blocking Vaccine (TBV) candidate antigens, which is expressed on the surface of male gametocytes and gametes of Plasmodium species. Since antigenic diversity could inhibit the successful development of a malaria vaccine, it is crucial to determine the diversity of gcs1 gene in global malaria-endemic areas. Therefore, gene diversity and selection of gcs1 gene were analyzed in Iranian Plasmodium vivax isolates (n=52) and compared with the corresponding sequences from worldwide clinical P. vivax isolates available in PlasmoDB database. Totally 12 SNPs were detected in the pvgcs1 sequences as compared to Sal-1 sequence. Five out of 12 SNPs including three synonymous (T797C, G1559A, and G1667T) and two amino acid replacements (Y133S and Q634P) were detected in Iranian pvgcs1 sequences. According to four amino acid replacements (Y133S, N575S, Q634P and D637N) observed in all world PvGCS1 sequences, totally 5 PvGCS1 haplotypes were detected in the world, that three of them observed in Iranian isolates including the PvGCS-A (133S/634Q, 92.3%), PvGCS-B (133Y/634Q, 5.8%), and PvGCS-C (133S/634P, 1.9%). The overall nucleotide diversity (pi) for all 52 sequences of Iranian pvgcs1 gene was 0.00018+/-0.00006, and the value of dN-dS (-0.00031) were negative, however, it was not statistically significant. In comparison with global isolates, Iranian and PNG pvgcs1 sequences had the lowest nucleotide and haplotype diversity, while the highest nucleotide and haplotype diversity was observed in China population. Moreover, epitope prediction in this antigen showed that all B-cell epitopes were located in conserved regions. However, Q634P (in one Iranian isolate) and D637N (observed in Thailand, China, Vietnam and North Korea) mutations are involved in predicted IURs. The obtained results in this study could be used in development of PvGCS1 based malaria vaccine. PMID- 27180895 TI - Distinguishing the genotype 1 genes and proteins of human Wa-like rotaviruses vs. porcine rotaviruses. AB - Group A rotaviruses (RVAs) are 11-segmented, double-stranded RNA viruses and important causes of gastroenteritis in the young of many animal species. Previous studies have suggested that human Wa-like RVAs share a close evolutionary relationship with porcine RVAs. Specifically, the VP1-VP3 and NSP2-5/6 genes of these viruses are usually classified as genotype 1 with >81% nucleotide sequence identity. Yet, it remains unknown whether the genotype 1 genes and proteins of human Wa-like strains are distinguishable from those of porcine strains. To investigate this, we performed comprehensive bioinformatic analyses using all known genotype 1 gene sequences. The RVAs analyzed represent wildtype strains isolated from humans or pigs at various geographical locations during the years of 2004-2013, including 11 newly-sequenced porcine RVAs from Brazil. We also analyzed archival strains that were isolated during the years of 1977-1992 as well as atypical strains involved in inter-species transmission between humans and pigs. We found that, in general, the genotype 1 genes of typical modern human Wa-like RVAs clustered together in phylogenetic trees and were separate from those of typical modern porcine RVAs. The only exception was for the NSP5/6 gene, which showed no host-specific phylogenetic clustering. Using amino acid sequence alignments, we identified 34 positions that differentiated the VP1-VP3, NSP2, and NSP3 genotype 1 proteins of typical modern human Wa-like RVAs versus typical modern porcine RVAs and documented how these positions vary in the archival/unusual isolates. No host-specific amino acid positions were identified for NSP4, NSP5, or NSP6. Altogether, the results of this study support the notion that human Wa-like RVAs and porcine RVAs are evolutionarily related, but indicate that some of their genotype 1 genes and proteins have diverged over time possibly as a reflection of sequestered replication and protein co-adaptation in their respective hosts. PMID- 27180896 TI - Molecular epidemiology, phylogeny and evolution of Legionella. AB - Legionella are opportunistic pathogens that develop in aquatic environments where they multiply in protozoa. When infected aerosols reach the human respiratory tract they may accidentally infect the alveolar macrophages leading to a severe pneumonia called Legionnaires' disease (LD). The ability of Legionella to survive within host-cells is strictly dependent on the Dot/Icm Type 4 Secretion System that translocates a large repertoire of effectors into the host cell cytosol. Although Legionella is a large genus comprising nearly 60 species that are worldwide distributed, only about half of them have been involved in LD cases. Strikingly, the species Legionella pneumophila alone is responsible for 90% of all LD cases. The present review summarizes the molecular approaches that are used for L. pneumophila genotyping with a major focus on the contribution of whole genome sequencing (WGS) to the investigation of local L. pneumophila outbreaks and global epidemiology studies. We report the newest knowledge regarding the phylogeny and the evolution of Legionella and then focus on virulence evolution of those Legionella species that are known to have the capacity to infect humans. Finally, we discuss the evolutionary forces and adaptation mechanisms acting on the Dot/Icm system itself as well as the role of mobile genetic elements (MGE) encoding T4ASSs and of gene duplications in the evolution of Legionella and its adaptation to different hosts and lifestyles. PMID- 27180897 TI - Phylogenetic analysis of the Trypanosoma genus based on the heat-shock protein 70 gene. AB - Trypanosome evolution was so far essentially studied on the basis of phylogenetic analyses of small subunit ribosomal RNA (SSU-rRNA) and glycosomal glyceraldehyde 3-phosphate dehydrogenase (gGAPDH) genes. We used for the first time the 70kDa heat-shock protein gene (hsp70) to investigate the phylogenetic relationships among 11 Trypanosoma species on the basis of 1380 nucleotides from 76 sequences corresponding to 65 strains. We also constructed a phylogeny based on combined datasets of SSU-rDNA, gGAPDH and hsp70 sequences. The obtained clusters can be correlated with the sections and subgenus classifications of mammal-infecting trypanosomes except for Trypanosoma theileri and Trypanosoma rangeli. Our analysis supports the classification of Trypanosoma species into clades rather than in sections and subgenera, some of which being polyphyletic. Nine clades were recognized: Trypanosoma carassi, Trypanosoma congolense, Trypanosoma cruzi, Trypanosoma grayi, Trypanosoma lewisi, T. rangeli, T. theileri, Trypanosoma vivax and Trypanozoon. These results are consistent with existing knowledge of the genus' phylogeny. Within the T. cruzi clade, three groups of T. cruzi discrete typing units could be clearly distinguished, corresponding to TcI, TcIII, and TcII+V+VI, while support for TcIV was lacking. Phylogenetic analyses based on hsp70 demonstrated that this molecular marker can be applied for discriminating most of the Trypanosoma species and clades. PMID- 27180898 TI - Association of MYF5 and KLF15 gene polymorphisms with carcass traits in domestic pigeons (Columba livia). AB - Single nucleotide polymorphisms (SNPs) in the exons of the myogenic factor 5 (MYF5) and Kruppel-like factor 15 (KLF15) genes were identified and analysed by using DNA sequencing methods in 60 female domestic pigeons (Columba livia). Five SNPs (T5067A, C5084T, C5101T, T5127A and C5154G) were detected in exon 3 of MYF5 and 6 SNPs (C1398T, C1464T, G1542A, C1929T, G1965A and A2355G) were found in exon 2 of KLF15, respectively. The analysis revealed three genotypes, in which the AA genotype was dominant and the A allele showed a dominant advantage. For the MYF5 gene, the C5084T and T5127A SNP genotypes were significantly associated with carcass traits of pigeons. Within those two SNPs, the BB genotype showed relatively higher trait association values than those of AA or AB genotypes. No significant association was observed between the KLF15 SNP genotypes and carcass traits. These results indicated that the MYF5 gene is a potential major gene affecting carcass traits in domestic pigeons. The BB genotype of the C5084T and T5127A SNPs could be a potential candidate genetic marker for marker-assisted selection in pigeon. PMID- 27180899 TI - Alcohol intake increases the risk of HCC in hepatitis C virus-related compensated cirrhosis: A prospective study. AB - BACKGROUND & AIMS: Whether alcohol intake increases the risk of complications in patients with HCV-related cirrhosis remains unclear. The aim of this study was to determine the impact of alcohol intake and viral eradication on the risk of hepatocellular carcinoma (HCC), decompensation of cirrhosis and death. METHODS: Data on alcohol intake and viral eradication were prospectively collected in 192 patients with compensated HCV-related cirrhosis. RESULTS: 74 patients consumed alcohol (median alcohol intake: 15g/day); 68 reached viral eradication. During a median follow-up of 58months, 33 patients developed HCC, 53 experienced at least one decompensation event, and 39 died. The 5-year cumulative incidence rate of HCC was 10.6% (95% CI: 4.6-16.6) in abstainers vs. 23.8% (95% CI: 13.5-34.1) in consumers (p=0.087), and 2.0% (95% CI: 0-5.8) vs. 21.7% (95% CI: 14.2-29.2) in patients with and without viral eradication (p=0.002), respectively. The lowest risk of HCC was observed for patients without alcohol intake and with viral eradication (0%) followed by patients with alcohol intake and viral eradication (6.2% [95% CI: 0-18.4]), patients without alcohol intake and no viral eradication (15.9% [95% CI: 7.1-24.7]), and patients with alcohol intake and no viral eradication (29.2% [95% CI: 16.5-41.9]) (p=0.009). In multivariate analysis, lack of viral eradication and alcohol consumption were associated with the risk of HCC (hazard ratio for alcohol consumption: 3.43, 95% CI: 1.49-7.92, p=0.004). Alcohol intake did not influence the risk of decompensation or death. CONCLUSIONS: Light to-moderate alcohol intake increases the risk of HCC in patients with HCV-related cirrhosis. Patient care should include measures to ensure abstinence. LAY SUMMARY: Whether alcohol intake increases the risk of complications in patients with HCV-related cirrhosis remains unclear. In this prospective study, light-to moderate alcohol intake was associated with the risk of hepatocellular carcinoma in multivariate analysis. No patients who did not use alcohol and who reached viral eradication developed hepatocellular carcinoma during follow-up. The risk of hepatocellular carcinoma increased with alcohol intake or in patients without viral eradication and was highest when alcohol intake was present in the absence of viral eradication. Patients with HCV-related cirrhosis should be strongly advised against any alcohol intake. Patient care should include measures to ensure abstinence. PMID- 27180901 TI - Brevibacillus laterosporus inside the insect body: Beneficial resident or pathogenic outsider? AB - Brevibacillus laterosporus is an entomopathogenic bacterium showing varying degrees of virulence against diverse insect pests. Conversely, it is regarded as a beneficial component of the intestinal flora in different animals and in some insect species including the honeybee. B. laterosporus was detected through a species-specific PCR assay in the body of different insects, including Apis mellifera and Bombus terrestris. A strain isolated from a honeybee worker was pathogenic to the house fly Musca domestica, thus supporting the development of either mutualistic or pathogenic interactions of this bacterium with diverse insect species, as the result of a coevolutionary process. PMID- 27180900 TI - Effect of Marriage on Risk for Onset of Alcohol Use Disorder: A Longitudinal and Co-Relative Analysis in a Swedish National Sample. AB - OBJECTIVE: The authors sought to clarify the relationship between marriage and risk for alcohol use disorder. METHOD: The association between marital status and risk for first registration for alcohol use disorder in medical, criminal, and pharmacy registries was assessed in a population-based Swedish cohort (N=3,220,628) using longitudinal time-dependent survival and co-relative designs. RESULTS: First marriage was associated with a substantial decline in risk for onset of alcohol use disorder in men (hazard ratio=0.41, 95% CI=0.40-0.42) and women (hazard ratio=0.27, 95% CI=0.26-0.28). This association was slightly stronger when the spouse had no lifetime alcohol use disorder, while marriage to a spouse with lifetime alcohol use disorder increased risk for subsequent alcohol use disorder registration in both men (hazard ratio=1.29, 95% CI=1.16-1.43) and women (hazard ratio=1.18, 95% CI=1.06-1.30). In both sexes, the protective effect of marriage was significantly stronger in those with than those without a family history of alcohol use disorder. In both men and women, the associations between marriage and risk for alcohol use disorder in cousins, half siblings, full siblings, and monozygotic twins discordant for marital status were as strong as that seen in the general population. CONCLUSIONS: First marriage to a spouse with no lifetime alcohol use disorder is associated with a large reduction in risk for alcohol use disorder. This association cannot be explained by standard covariates or, as indicated by co-relative analyses, familial genetic or shared environmental confounders. These results are consistent with the hypothesis that the psychological and social aspects of marriage, and in particular health monitoring spousal interactions, strongly protect against the development of alcohol use disorder. The protective effects of marriage on risk for alcohol use disorder are increased in those at high familial risk for alcoholism. PMID- 27180902 TI - A novel WS2 nanowire-nanoflake hybrid material synthesized from WO3 nanowires in sulfur vapor. AB - In this work, WS2 nanowire-nanoflake hybrids are synthesized by the sulfurization of hydrothermally grown WO3 nanowires. The influence of temperature on the formation of products is optimized to grow WS2 nanowires covered with nanoflakes. Current-voltage and resistance-temperature measurements carried out on random networks of the nanostructures show nonlinear characteristics and negative temperature coefficient of resistance indicating that the hybrids are of semiconducting nature. Bottom gated field effect transistor structures based on random networks of the hybrids show only minor modulation of the channel conductance upon applied gate voltage, which indicates poor electrical transport between the nanowires in the random films. On the other hand, the photo response of channel current holds promise for cost-efficient solution process fabrication of photodetector devices working in the visible spectral range. PMID- 27180903 TI - Deciphering the relationship among phosphate dynamics, electron-dense body and lipid accumulation in the green alga Parachlorella kessleri. AB - Phosphorus is an essential element for life on earth and is also important for modern agriculture, which is dependent on inorganic fertilizers from phosphate rock. Polyphosphate is a biological polymer of phosphate residues, which is accumulated in organisms during the biological wastewater treatment process to enhance biological phosphorus removal. Here, we investigated the relationship between polyphosphate accumulation and electron-dense bodies in the green alga Parachlorella kessleri. Under sulfur-depleted conditions, in which some symporter genes were upregulated, while others were downregulated, total phosphate accumulation increased in the early stage of culture compared to that under sulfur-replete conditions. The P signal was detected only in dense bodies by energy dispersive X-ray analysis. Transmission electron microscopy revealed marked ultrastructural variations in dense bodies with and without polyphosphate. Our findings suggest that the dense body is a site of polyphosphate accumulation, and P. kessleri has potential as a phosphate-accumulating organism. PMID- 27180904 TI - Sterol-Rich Membrane Domains Define Fission Yeast Cell Polarity. AB - Cell polarization is crucial for the functioning of all organisms. The cytoskeleton is central to the process but its role in symmetry breaking is poorly understood. We study cell polarization when fission yeast cells exit starvation. We show that the basis of polarity generation is de novo sterol biosynthesis, cell surface delivery of sterols, and their recruitment to the cell poles. This involves four phases occurring independent of the polarity factor cdc42p. Initially, multiple, randomly distributed sterol-rich membrane (SRM) domains form at the plasma membrane, independent of the cytoskeleton and cell growth. These domains provide platforms on which the growth and polarity machinery assembles. SRM domains are then polarized by the microtubule-dependent polarity factor tea1p, which prepares for monopolar growth initiation and later switching to bipolar growth. SRM polarization requires F-actin but not the F actin organizing polarity factors for3p and bud6p. We conclude that SRMs are key to cell polarization. PMID- 27180905 TI - RNA Duplex Map in Living Cells Reveals Higher-Order Transcriptome Structure. AB - RNA has the intrinsic property to base pair, forming complex structures fundamental to its diverse functions. Here, we develop PARIS, a method based on reversible psoralen crosslinking for global mapping of RNA duplexes with near base-pair resolution in living cells. PARIS analysis in three human and mouse cell types reveals frequent long-range structures, higher-order architectures, and RNA-RNA interactions in trans across the transcriptome. PARIS determines base pairing interactions on an individual-molecule level, revealing pervasive alternative conformations. We used PARIS-determined helices to guide phylogenetic analysis of RNA structures and discovered conserved long-range and alternative structures. XIST, a long noncoding RNA (lncRNA) essential for X chromosome inactivation, folds into evolutionarily conserved RNA structural domains that span many kilobases. XIST A-repeat forms complex inter-repeat duplexes that nucleate higher-order assembly of the key epigenetic silencing protein SPEN. PARIS is a generally applicable and versatile method that provides novel insights into the RNA structurome and interactome. VIDEO ABSTRACT. PMID- 27180906 TI - SIRT6 Suppresses Pancreatic Cancer through Control of Lin28b. AB - Chromatin remodeling proteins are frequently dysregulated in human cancer, yet little is known about how they control tumorigenesis. Here, we uncover an epigenetic program mediated by the NAD(+)-dependent histone deacetylase Sirtuin 6 (SIRT6) that is critical for suppression of pancreatic ductal adenocarcinoma (PDAC), one of the most lethal malignancies. SIRT6 inactivation accelerates PDAC progression and metastasis via upregulation of Lin28b, a negative regulator of the let-7 microRNA. SIRT6 loss results in histone hyperacetylation at the Lin28b promoter, Myc recruitment, and pronounced induction of Lin28b and downstream let 7 target genes, HMGA2, IGF2BP1, and IGF2BP3. This epigenetic program defines a distinct subset with a poor prognosis, representing 30%-40% of human PDAC, characterized by reduced SIRT6 expression and an exquisite dependence on Lin28b for tumor growth. Thus, we identify SIRT6 as an important PDAC tumor suppressor and uncover the Lin28b pathway as a potential therapeutic target in a molecularly defined PDAC subset. PAPERCLIP. PMID- 27180907 TI - A Mechanogenetic Toolkit for Interrogating Cell Signaling in Space and Time. AB - Tools capable of imaging and perturbing mechanical signaling pathways with fine spatiotemporal resolution have been elusive, despite their importance in diverse cellular processes. The challenge in developing a mechanogenetic toolkit (i.e., selective and quantitative activation of genetically encoded mechanoreceptors) stems from the fact that many mechanically activated processes are localized in space and time yet additionally require mechanical loading to become activated. To address this challenge, we synthesized magnetoplasmonic nanoparticles that can image, localize, and mechanically load targeted proteins with high spatiotemporal resolution. We demonstrate their utility by investigating the cell-surface activation of two mechanoreceptors: Notch and E-cadherin. By measuring cellular responses to a spectrum of spatial, chemical, temporal, and mechanical inputs at the single-molecule and single-cell levels, we reveal how spatial segregation and mechanical force cooperate to direct receptor activation dynamics. This generalizable technique can be used to control and understand diverse mechanosensitive processes in cell signaling. VIDEO ABSTRACT. PMID- 27180908 TI - High-Throughput, High-Resolution Mapping of Protein Localization in Mammalian Brain by In Vivo Genome Editing. AB - A scalable and high-throughput method to identify precise subcellular localization of endogenous proteins is essential for integrative understanding of a cell at the molecular level. Here, we developed a simple and generalizable technique to image endogenous proteins with high specificity, resolution, and contrast in single cells in mammalian brain tissue. The technique, single-cell labeling of endogenous proteins by clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9-mediated homology-directed repair (SLENDR), uses in vivo genome editing to insert a sequence encoding an epitope tag or a fluorescent protein to a gene of interest by CRISPR-Cas9-mediated homology directed repair (HDR). Single-cell, HDR-mediated genome editing was achieved by delivering the editing machinery to dividing neuronal progenitors through in utero electroporation. We demonstrate that SLENDR allows rapid determination of the localization and dynamics of many endogenous proteins in various cell types, regions, and ages in the brain. Thus, SLENDR provides a high-throughput platform to map the subcellular localization of endogenous proteins with the resolution of micro- to nanometers in the brain. PMID- 27180910 TI - Scatter to volume registration for model-free respiratory motion estimation from dynamic MRIs. AB - Respiratory motion is one major complicating factor in many image acquisition applications and image-guided interventions. Existing respiratory motion estimation and compensation methods typically rely on breathing motion models learned from certain training data, and therefore may not be able to effectively handle intra-subject and/or inter-subject variations of respiratory motion. In this paper, we propose a respiratory motion compensation framework that directly recovers motion fields from sparsely spaced and efficiently acquired dynamic 2-D MRIs without using a learned respiratory motion model. We present a scatter-to volume deformable registration algorithm to register dynamic 2-D MRIs with a static 3-D MRI to recover dense deformation fields. Practical considerations and approximations are provided to solve the scatter-to-volume registration problem efficiently. The performance of the proposed method was investigated on both synthetic and real MRI datasets, and the results showed significant improvements over the state-of-art respiratory motion modeling methods. We also demonstrated a potential application of the proposed method on MRI-based motion corrected PET imaging using hybrid PET/MRI. PMID- 27180909 TI - Two common structural motifs for TCR recognition by staphylococcal enterotoxins. AB - Superantigens are toxins produced by Staphylococcus aureus, called staphylococcal enterotoxins (abbreviated SEA to SEU). They can cross-link the T cell receptor (TCR) and major histocompatibility complex class II, triggering a massive T cell activation and hence disease. Due to high stability and toxicity, superantigens are potential agents of bioterrorism. Hence, antagonists may not only be useful in the treatment of disease but also serve as countermeasures to biological warfare. Of particular interest are inhibitors against SEA and SEB. SEA is the main cause of food poisoning, while SEB is a common toxin manufactured as a biological weapon. Here, we present the crystal structures of SEA in complex with TCR and SEE in complex with the same TCR, complemented with computational alanine scanning mutagenesis of SEA, SEB, SEC3, SEE, and SEH. We have identified two common areas that contribute to the general TCR binding for these superantigens. This paves the way for design of single antagonists directed towards multiple toxins. PMID- 27180911 TI - Prediction of alcohol drinking in adolescents: Personality-traits, behavior, brain responses, and genetic variations in the context of reward sensitivity. AB - Adolescence is a time that can set the course of alcohol abuse later in life. Sensitivity to reward on multiple levels is a major factor in this development. We examined 736 adolescents from the IMAGEN longitudinal study for alcohol drinking during early (mean age=14.37) and again later (mean age=16.45) adolescence. Conducting structural equation modeling we evaluated the contribution of reward-related personality traits, behavior, brain responses and candidate genes. Personality seems to be most important in explaining alcohol drinking in early adolescence. However, genetic variations in ANKK1 (rs1800497) and HOMER1 (rs7713917) play an equal role in predicting alcohol drinking two years later and are most important in predicting the increase in alcohol consumption. We hypothesize that the initiation of alcohol use may be driven more strongly by personality while the transition to increased alcohol use is more genetically influenced. PMID- 27180913 TI - Attention-deficit hyperactivity disorder and children's emotion dysregulation: A meta-analysis. AB - While executive functioning deficits have been central to cognitive theories of Attention-Deficit Hyperactivity Disorder (ADHD), recent work has suggested that emotion dysregulation may also play a key role in understanding the impairments suffered by youth with ADHD. However, given the multiple processes involved in emotion dysregulation, the extent to which youth with ADHD are impaired across multiple domains of emotion dysregulation including: emotion recognition/understanding (ERU), emotion reactivity/negativity/lability (ERNL), emotion regulation (EREG), and empathy/callous-unemotional traits (ECUT) remains unclear. A meta-analysis of 77 studies (n=32,044 youths) revealed that youth with ADHD have the greatest impairment on ERNL (weighted ES d=.95) followed by EREG (weighted ES d=.80). Significantly smaller effects were observed for ECUT (weighted ES d=.68) and ERU (weighted ES d=.64). Moderation analyses indicated that the association between ADHD and ERNL was stronger among studies that had a sample containing older youth (no other demographic factors were significant). Additionally, the association between ADHD and ECUT was significantly weaker among studies that controlled for co-occurring conduct problems. Co-occurring conduct problems did not moderate the link between ADHD and any other emotion dysregulation domain. Lastly, the association between ADHD and ERNL was significantly weaker when controlling for youth's cognitive functioning. Cognitive functioning did not moderate the link between ADHD and ERU, EREG, or ECUT, respectively. Theoretical/practical implications for the study of emotional dysregulation in youth with ADHD are discussed. PMID- 27180912 TI - Iso-acoustic focusing of cells for size-insensitive acousto-mechanical phenotyping. AB - Mechanical phenotyping of single cells is an emerging tool for cell classification, enabling assessment of effective parameters relating to cells' interior molecular content and structure. Here, we present iso-acoustic focusing, an equilibrium method to analyze the effective acoustic impedance of single cells in continuous flow. While flowing through a microchannel, cells migrate sideways, influenced by an acoustic field, into streams of increasing acoustic impedance, until reaching their cell-type specific point of zero acoustic contrast. We establish an experimental procedure and provide theoretical justifications and models for iso-acoustic focusing. We describe a method for providing a suitable acoustic contrast gradient in a cell-friendly medium, and use acoustic forces to maintain that gradient in the presence of destabilizing forces. Applying this method we demonstrate iso-acoustic focusing of cell lines and leukocytes, showing that acoustic properties provide phenotypic information independent of size. PMID- 27180914 TI - Circulating Zinc-alpha2-glycoprotein levels and Insulin Resistance in Polycystic Ovary Syndrome. AB - The aim of study was to assess the relationship between zinc-alpha2-glycoprotein (ZAG) and androgen excess with insulin resistance in polycystic ovary syndrome (PCOS) women. 99 PCOS women and 100 healthy controls were recruited. Euglycemic hyperinsulinemic clamp (EHC) was preformed to assess their insulin sensitivity. Circulating ZAG was determined with an ELISA kit. In healthy subjects, circulating ZAG levels exhibited a characteristic diurnal rhythm in humans, with a major nocturnal rise occurring between midnight and early morning. Circulating ZAG and M-value were much lower in PCOS women than in the controls. In all population, overweight/obese subjects had significantly lower circulating ZAG levels than lean individuals. Multiple linear regression analysis revealed that only M-value and the area under the curve for glucose were independently related factors to circulating ZAG in PCOS women. Multivariate logistic regression analysis showed that circulating ZAG was significantly associated with PCOS even after controlling for anthropometric variables, blood pressure, lipid profile and hormone levels. The PCOS women with high ZAG had fewer MetS, IGT and polycystic ovaries as compared with the low ZAG PCOS women. Taken together, circulating ZAG levels are reduced in women with PCOS and ZAG may be a cytokine associated with insulin resistance in PCOS women. PMID- 27180915 TI - Cystic Lung Diseases: Algorithmic Approach. AB - Cysts are commonly seen on CT scans of the lungs, and diagnosis can be challenging. Clinical and radiographic features combined with a multidisciplinary approach may help differentiate among various disease entities, allowing correct diagnosis. It is important to distinguish cysts from cavities because they each have distinct etiologies and associated clinical disorders. Conditions such as emphysema, and cystic bronchiectasis may also mimic cystic disease. A simplified classification of cysts is proposed. Cysts can occur in greater profusion in the subpleural areas, when they typically represent paraseptal emphysema, bullae, or honeycombing. Cysts that are present in the lung parenchyma but away from subpleural areas may be present without any other abnormalities on high resolution CT scans. These are further categorized into solitary or multifocal/diffuse cysts. Solitary cysts may be incidentally discovered and may be an age related phenomenon or may be a remnant of prior trauma or infection. Multifocal/diffuse cysts can occur with lymphoid interstitial pneumonia, Birt Hogg-Dube syndrome, tracheobronchial papillomatosis, or primary and metastatic cancers. Multifocal/diffuse cysts may be associated with nodules (lymphoid interstitial pneumonia, light-chain deposition disease, amyloidosis, and Langerhans cell histiocytosis) or with ground-glass opacities (Pneumocystis jirovecii pneumonia and desquamative interstitial pneumonia). Using the results of the high-resolution CT scans as a starting point, and incorporating the patient's clinical history, physical examination, and laboratory findings, is likely to narrow the differential diagnosis of cystic lesions considerably. PMID- 27180916 TI - Establishing Pulmonary and Critical Care Medicine in China: 2016 Report on Implementation and Government Recognition: Joint Statement of the Chinese Association of Chest Physicians and the American College of Chest Physicians. AB - This article provides an update on progress toward establishing pulmonary and critical care medicine (PCCM) fellowship training as one of the first four subspecialties to be recognized and supported by the Chinese government. Designed and implemented throughout 2013 and 2014 by a collaborative effort of the Chinese Thoracic Society (CTS) and the American College of Chest Physicians (CHEST), 12 leading Chinese hospitals enrolled a total of 64 fellows into standardized PCCM training programs with common curricula, educational activities, and assessment measures. Supplemental educational materials, online assessment tools, and institutional site visits designed to evaluate and provide feedback on the programs' progress are being provided by CHEST. As a result of this initial progress, the Chinese government, through the Chinese Medical Doctor's Association, endorsed the concept of subspecialty fellowship training in China, with PCCM as one of the four pilot subspecialties to be operationalized nationwide in 2016, followed by implementation across other subspecialties by 2020. This article also reflects on the achievements of the training sites and the challenges they face and outlines plans to enhance and expand PCCM training and practice in China. PMID- 27180921 TI - Serum homocysteine level and gestational diabetes mellitus: A meta-analysis. AB - AIMS/INTRODUCTION: Homocysteine levels during pregnancy in women with gestational diabetes mellitus (GDM) have been studied; however, it remains unclear whether hyperhomocysteinemia is a useful predictor of insulin resistance. The present study aimed to evaluate the relationship between homocysteine level and GDM. MATERIALS AND METHODS: PubMed, Elsevier, Web of Science and CNKI were searched for relevant studies published up to January 2015. Manual searches of references of the relevant original studies were carried out. Meta-analysis was used to assessed the relationship between homocysteine level and GDM using the stata 12.0 software. RESULTS: Homocysteine levels were significantly elevated in women with GDM compared with those without GDM (weighted mean difference 0.77, 95% confidence interval 0.44-1.10). This evidence was more consistent during the second trimester measurement of homocysteine (weighted mean difference 0.95, 95% confidence interval 0.67-1.23) and for women aged older than 30 years (weighted mean difference 0.90, 95% confidence interval 0.63-1.17). CONCLUSIONS: The present meta-analysis shows that homocysteine level is significantly elevated among women with GDM compared with women with normal glucose tolerance, and this finding persists more during the second trimester. PMID- 27180922 TI - A Biomechanical Analysis of Different Clavicular Tunnel Diameters in Anatomic Acromioclavicular Ligament Reconstruction. AB - PURPOSE: To evaluate the biomechanical stability of a tendon-to-clavicle bone interface fixation of a graft in revision acromioclavicular reconstruction. METHODS: Fifteen fresh-frozen cadaveric shoulders were used. All specimens underwent bone density evaluation. For the primary reconstruction, a 5-mm semitendinosus allograft was inserted into a 5-mm bone tunnel at 25 and 45 mm from the lateral end of the clavicle using a 5.5 * 8-mm PEEK (polyether ether ketone) tenodesis screw. Each single graft was fixed in a cryo-clamp and cyclically loaded from 5 to 70 N for 3,000 cycles, followed by load-to-failure testing at a rate of 120 mm/min to simulate the revision case. To simulate tunnel widening, the tunnels of the revision series were over-drilled with an 8-mm drill, and a 5-mm semitendinosus graft with an 8 * 12-mm PEEK tenodesis screw was inserted. Biomechanical testing was then repeated. RESULTS: The bone mineral density analysis showed a significantly higher density at the 45-mm hole compared with the 25-mm hole (P = .001). The ultimate load to failure increased from the 5.5-mm screw to the 8-mm screw at the 45-mm hole position (P = .001). There was no statistically significant difference at the 25-mm hole position (P = .934). No statistical significance for graft elongation comparing the 5.5-mm screw and the 8-mm screw at the 25-mm (P = .156) and 45-mm (P = .334) positions could be found. CONCLUSIONS: Comparable biomechanical stability for the tendon-to-bone interface fixation in different clavicular tunnel diameters simulating primary and revision reconstruction was achieved. CLINICAL RELEVANCE: There is a lack of literature regarding revision acromioclavicular joint reconstruction, but our biomechanical results show comparable stability to primary reconstruction. These data provide support for the use of anatomic acromioclavicular ligament reconstruction in revision cases. PMID- 27180923 TI - Shoulder Stiffness: Current Concepts and Concerns. AB - Shoulder stiffness can be caused by various etiologies such as immobilization, trauma, or surgical interventions. The Upper Extremity Committee of ISAKOS defined the term "frozen shoulder" as idiopathic stiff shoulder, that is, without a known cause. Secondary stiff shoulder is a term that should be used to describe shoulder stiffness with a known cause. The pathophysiology of frozen shoulder is capsular fibrosis and inflammation with chondrogenesis, but the cause is still unknown. Conservative treatment is the primary choice. Pain control by oral medication, intra-articular injections with or without joint distension, and physical therapy are commonly used. In cases with refractory stiffness, manipulation under anesthesia or arthroscopic capsular release may be indicated. Because of various potential risks of complications with manipulations, arthroscopic capsular release is preferred. After the capsular release, stepwise rehabilitation is mandatory to achieve satisfactory outcome. LEVEL OF EVIDENCE: Level V, evidence-based review. PMID- 27180924 TI - Involvement of Transient Receptor Potential Vanilloid (TRPV) 4 in mouse sperm thermotaxis. AB - Transient Receptor Potential Vanilloid (TRPV) 4 is one of the temperature sensitive ion channels involved in temperature receptors, and it is known to be activated from 35 to 40oC. Here we analyzed sperm motility function of Trpv4 knockout (KO) mouse in temperature-gradient conditions to elucidate the thermotaxis of mouse sperm and the involvement of TRPV4 in thermotaxis. The sperm were introduced at the vertical column end of a T-shaped chamber filled with medium in a plastic dish, and we measured the number of sperm that arrived at both ends of the wide column where we had established a temperature gradient of approx. 2oC, and we evaluated the sperm's thermotaxis. Large numbers of wild-type (WT) mouse sperm migrated into the high level of the temperature gradient that was set in the wide column, and thermotaxis was confirmed. The ratio of migrated sperm at the high temperature level of the T-shaped chamber was decreased in the KO sperm and Ruthenium red (a TRPV antagonist) treated sperm compared with the WT sperm. The thermotaxis of the mouse sperm was confirmed, and the involvement of TRPV4 in this thermotaxis was suggested. PMID- 27180925 TI - Mouse oocytes suppress miR-322-5p expression in ovarian granulosa cells. AB - This study tested the hypothesis that oocyte-derived paracrine factors (ODPFs) regulate miRNA expression in mouse granulosa cells. Expression of mmu-miR-322-5p (miR-322) was higher in mural granulosa cells (MGCs) than in cumulus cells of the Graafian follicles. The expression levels of miR-322 decreased when cumulus cells or MGCs were co-cultured with oocytes denuded of their cumulus cells. Inhibition of SMAD2/3 signaling by SB431542 increased miR-322 expression by cumulus-oocyte complexes (COCs). Moreover, the cumulus cells but not the MGCs in Bmp15(-/ )/Gdf9(+/-) (double-mutant) mice exhibited higher miR-322 expression than those of wild-type mice. Taken together, these results show that ODPFs suppress the expression of miR-322 in cumulus cells. Gene ontology analysis of putative miR 322 targets whose expression was detected in MGCs with RNA-sequencing suggested that multiple biological processes are affected by miR-322 in MGCs. These results demonstrate that ODPFs regulate miRNA expression in granulosa cells and that this regulation may participate in the differential control of cumulus cell versus MGC functions. Therefore, the ODPF-mediated regulation of cumulus cells takes place at both transcriptional and post-transcriptional levels. PMID- 27180926 TI - Secukinumab long-term safety experience: A pooled analysis of 10 phase II and III clinical studies in patients with moderate to severe plaque psoriasis. AB - BACKGROUND: Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, has demonstrated efficacy and safety in patients with moderate to severe plaque psoriasis. OBJECTIVE: We reviewed safety data from the secukinumab psoriasis phase II/III program. METHODS: Data were pooled from 10 phase II/III secukinumab psoriasis studies. RESULTS: Analysis included 3993 subjects; 3430 received secukinumab, representing 2725 subject-years (SYs) of exposure. Over 52 weeks, for secukinumab 300 mg, 150 mg, and etanercept, respectively, exposure-adjusted incidence rates (IRs) per 100 SYs were comparable across treatments for total adverse events (AEs; 236.1, 239.9, and 243.4, respectively); infections (91.1, 85.3, and 93.7, respectively); serious AEs (7.4, 6.8, and 7.0, respectively); serious infections (1.4, 1.1, and 1.4, respectively); malignant or unspecified tumors (0.77, 0.97, and 0.68, respectively); and adjudicated major adverse cardiovascular events (0.42, 0.35, and 0.34, respectively). AEs were not dose related except for nonserious, mild/moderate, skin/mucosal candidiasis (IRs 3.55, 1.85, and 1.37 for secukinumab 300 mg, 150 mg, and etanercept, respectively). LIMITATIONS: There was a limited number of patients in comparator groups and the exposure to placebo was short. CONCLUSION: Secukinumab had a favorable safety profile, had no meaningful difference between the 300- and 150-mg doses and, in terms of safety, was comparable to etanercept over 52 weeks in patients with moderate to severe plaque psoriasis. PMID- 27180928 TI - Log Odds of Positive Lymph Nodes Predicts Survival in Patients After Resection for Esophageal Cancer. AB - BACKGROUND: The number of lymph node metastases (LNMs) and the positive lymph node ratio (LNR) have been shown to be significant independent prognostic factors in predicting overall survival in patients with esophageal cancer. Our aim was to evaluate whether a novel prognostic indicator-the log odds of positive lymph nodes (LODDS)-predicts survival in esophageal cancer. METHODS: Patients who underwent esophagectomy for esophageal cancer between 1988 and 2007 were identified from the Surveillance, Epidemiology, and End Results (SEER) database of 18 registries, and a Chinese patient cohort was subjected to validation. The prognostic efficacy of LNM, LNR, and LODDS was compared. Prognostic performance was measured using Harrell's C-index statistic, Schemper's proportion of explained variation, and the Akaike information criterion (AIC). RESULTS: A total of 4,123 patients in the SEER database and 134 patients in the Chinese cohort met our criteria in this study. LODDS gave a better prognostic performance than either LNM or LNR in both the SEER database and the Chinese cohort. Multivariate analyses showed significant values for LNM, LNR, and LODDS as prognostic factors (p < 0.001). However, only LODDS was a significant prognostic factor regardless of the number of lymph nodes retrieved (p = 0.677). Furthermore, after stratification of patients with no nodes involved or all nodes involved, the values of LODDS still distinguished the heterogeneity efficiently. CONCLUSIONS: LODDS predicts survival more accurately than either LNM or LNR in patients undergoing resection for esophageal cancer, especially for patients with an insufficient number of lymph nodes retrieved. PMID- 27180927 TI - Predictors for mortality from respiratory failure in a general population. AB - Risk factors for death from respiratory failure in the general population are not established. The aim of this study was to determine the characteristics of individuals who die of respiratory failure in a Japanese general population. In total, 3253 adults aged 40 years or older participated in annual health check in Takahata, Yamagata, Japan from 2004 to 2006. Subject deaths through the end of 2010 were reviewed; 27 subjects died of respiratory failure (pneumonia, n = 22; COPD, n = 1; pulmonary fibrosis, n = 3; and bronchial asthma, n = 1). Cox proportional hazard analysis revealed that male sex; higher age, high levels of D dimer and fibrinogen; lower body mass index (BMI) and total cholesterol; and history of stroke and gastric ulcer were independent risk factors for respiratory death. On analysis with C-statistics, net reclassification improvement, and integrated discrimination improvement, addition of the disease history and laboratory data significantly improved the model prediction for respiratory death using age and BMI. In conclusion, we identified risk factors for mortality from respiratory failure in a prospective cohort of a Japanese general population. Men who were older, underweight, hypocholesterolemic, hypercoagulo-fibrinolytic, and had a history of stroke or gastric ulcer had a higher risk of mortality due to respiratory failure. PMID- 27180930 TI - Unbiased and robust quantification of synchronization between spikes and local field potential. AB - BACKGROUND: In neuroscience, relating the spiking activity of individual neurons to the local field potential (LFP) of neural ensembles is an increasingly useful approach for studying rhythmic neuronal synchronization. Many methods have been proposed to measure the strength of the association between spikes and rhythms in the LFP recordings, and most existing measures are dependent upon the total number of spikes. NEW METHOD: In the present work, we introduce a robust approach for quantifying spike-LFP synchronization which performs reliably for limited samples of data. The measure is termed as spike-triggered correlation matrix synchronization (SCMS), which takes LFP segments centered on each spike as multi channel signals and calculates the index of spike-LFP synchronization by constructing a correlation matrix. RESULTS: The simulation based on artificial data shows that the SCMS output almost does not change with the sample size. This property is of crucial importance when making comparisons between different experimental conditions. When applied to actual neuronal data recorded from the monkey primary visual cortex, it is found that the spike-LFP synchronization strength shows orientation selectivity to drifting gratings. COMPARISON WITH EXISTING METHODS: In comparison to another unbiased method, pairwise phase consistency (PPC), the proposed SCMS behaves better for noisy spike trains by means of numerical simulations. CONCLUSIONS: This study demonstrates the basic idea and calculating process of the SCMS method. Considering its unbiasedness and robustness, the measure is of great advantage to characterize the synchronization between spike trains and rhythms present in LFP. PMID- 27180929 TI - Vitamin D and its receptor regulate lipopolysaccharide-induced transforming growth factor-beta, angiotensinogen expression and podocytes apoptosis through the nuclear factor-kappaB pathway. AB - AIMS/INTRODUCTION: To investigate the effects of vitamin D and its receptor on cytokines expression and podocytes apoptosis. MATERIALS AND METHODS: Cultured mouse podocytes were pre-incubated with vitamin D or transiently transfected with small interfering ribonucleic acid (RNA) to knock down the vitamin D receptor. Lipopolysaccharide was used to mimic the inflammation status of diabetes. RESULTS: In a lipopolysaccharide-induced state, expressions of transforming growth factor-beta, angiotensinogen and vascular endothelial growth factor were similarly increased. Transforming growth factor-beta and angiotensinogen levels originally elevated by lipopolysaccharide challenge were distinctly reduced after pre-incubation with vitamin D. Whereas after vitamin D receptor small interfering (si)RNA transfection, the aforementioned cytokines had opposite changes as expected. However, neither vitamin D pretreatment nor vitamin D receptor siRNA transfection influenced the previously increased vascular endothelial growth factor expression at messenger RNA or protein levels. When pretreated with vitamin D, decreases were observed for phosphorylated inhibitor-kappaB and the inhibitor kinase proteins. After siRNA transfection, those proteins levels were further elevated. The originally increased transforming growth factor-beta and angiotensinogen levels as a result of lipopolysaccharide stimulation were reduced at both the messenger RNA and protein levels after the specific inhibition of the nuclear factor-kappaB pathway with pyrrolidine dithiocarbamate. The apoptosis rate of podocytes was decreased in a parallel manner after vitamin D pre incubation, and increased after siRNA transfection, which was also suppressed by pyrrolidine dithiocarbamate. CONCLUSIONS: Vitamin D and its receptor might be involved in the progression of diabetic nephropathy by regulating transforming growth factor-beta, angiotensinogen expression and apoptosis of podocytes. The processes are mediated through the signaling of nuclear factor-kappaB pathway. PMID- 27180931 TI - Asian Dust and Pediatric Emergency Department Visits Due to Bronchial Asthma and Respiratory Diseases in Nagasaki, Japan. AB - BACKGROUND: The adverse health effects of Asian dust (AD) on the respiratory system of children are unclear. We hypothesized that AD events may lead to increased visits by children to emergency medical centers due to bronchial asthma and respiratory diseases, including bronchial asthma. METHODS: We used anonymized data on children receiving primary emergency treatment at Nagasaki Municipal Primary Emergency Medical Center, Japan between March 2010 and September 2013. We used Light Detection and Ranging (LIDAR) data to assess AD exposure and performed time-stratified case-crossover analyses to examine the association between AD exposure and emergency department visits. The main analysis was done with data collected from March through May each year. RESULTS: The total number of emergency department visits during the study period was 756 for bronchial asthma and 5421 for respiratory diseases, and the number of "AD days" was 47. In school children, AD events at lag day 3 and lag day 4 were associated with increased emergency department visits due to bronchial asthma, with odds ratios of 1.837 (95% confidence interval [CI], 1.212-2.786) and 1.829 (95% CI, 1.179-2.806), respectively. AD events were significantly associated with respiratory diseases among preschool children at lag day 0, lag day 1, and lag day 2, with odds ratios of 1.244 (95% CI, 1.128-1.373), 1.314 (95% CI, 1.189-1.452), and 1.273 (95% CI, 1.152-1.408), respectively. These associations were also significant when the results were adjusted for meteorological variables and other air pollutants. CONCLUSIONS: The study findings suggested that AD exposure increases emergency department visits by children. PMID- 27180932 TI - Tea and Risk of Age-Related Cataracts: A Cross-Sectional Study in Zhejiang Province, China. AB - BACKGROUND: The antioxidant properties of tea extracts are considered to be effective in protecting against cataracts. However, there is still insufficient epidemiological knowledge about the protective effects of different types of tea on age-related cataracts. METHODS: The data was derived from the Zhejiang Major Public Health Surveillance (ZJMPHS) Program on health and related factors in the elderly. The relationships between consumption of different types of tea and risk of age-related cataracts were assessed after adjusting for related covariates. RESULTS: The prevalence of age-related cataracts in this study population was 4.4% (409/9343). After adjustment for potential confounders, tea drinking was associated with reduced risk of age-related cataracts (adjusted odds ratio [OR] 0.65; 95% confidence interval [CI], 0.47-0.91). Compared to nondrinkers, green tea drinkers had a significantly reduced risk of cataracts (adjusted OR 0.58; 95% CI, 0.40-0.85). Average tea consumption of 14-27 cups (adjusted OR 0.55; 95% CI, 0.33-0.93) and over 28 cups (adjusted OR 0.58; 95% CI, 0.34-0.99) per week had a protective effect against cataracts in comparison to no consumption. In addition, ingesting a moderate concentration of tea significantly decreased the risk of cataract compared to no consumption (adjusted OR 0.43; 95% CI, 0.27-0.71). CONCLUSIONS: Tea ingestion was associated with reduced risk of age-related cataracts. In light of these findings, we suggest that reasonable tea consumption (ie, favoring green tea and consuming an average of over 500 mL per day at moderate concentration) should offer protection against age-related cataracts. PMID- 27180933 TI - Association Between Social Participation and Instrumental Activities of Daily Living Among Community-Dwelling Older Adults. AB - BACKGROUND: Population-based data examining the relationship between social participation (SP) and instrumental activities of daily living (IADL) are scarce. This study examined the cross-sectional relationship between SP and IADL in community-dwelling elderly persons. METHODS: Self-administered questionnaires were mailed to 23 710 residents aged >=65 years in Nara, Japan (response rate: 74.2%). Data from 14 956 respondents (6935 males and 8021 females) without dependency in basic activities of daily living (ADL) were analyzed. The number, type, and frequency of participation in social groups (SGs) were used to measure SP. SGs included volunteer groups, sports groups, hobby groups, senior citizens' clubs, neighborhood community associations, and cultural groups. IADL was evaluated using the Tokyo Metropolitan Institute of Gerontology Index of Competence. Logistic regression models stratified by gender were used. RESULTS: After adjustment for putative confounding factors, including demographics, health status, life-style habits, ADL, depression, cognitive function, social networks, social support, and social roles, participation in various SGs among both genders was inversely associated with poor IADL, showing a significant dose-response relationship between an increasing number of SGs and a lower proportion of those with poor IADL (P for trend <0.001). A significant inverse association between frequent participation and poor IADL was observed for all types of SGs among females, whereas the association was limited to sports groups and senior citizens' clubs among males. CONCLUSIONS: Our results show that participation in a variety of SGs is associated with independent IADL among the community-dwelling elderly, regardless of gender. However, the beneficial effects of frequent participation on IADL may be stronger for females than for males. PMID- 27180934 TI - Informal and Formal Social Support and Caregiver Burden: The AGES Caregiver Survey. AB - BACKGROUND: We examined the associations of informal (eg, family members and friends) and formal (eg, physician and visiting nurses) social support with caregiver's burden in long-term care and the relationship between the number of available sources of social support and caregiver burden. METHODS: We conducted a mail-in survey in 2003 and used data of 2998 main caregivers of frail older adults in Aichi, Japan. We used a validated scale to assess caregiver burden. RESULTS: Multiple linear regression demonstrated that, after controlling for caregivers' sociodemographic and other characteristics, informal social support was significantly associated with lower caregiver burden (beta = -1.59, P < 0.0001), while formal support was not (beta = -0.30, P = 0.39). Evaluating the associations by specific sources of social support, informal social supports from the caregiver's family living together (beta = -0.71, P < 0.0001) and from relatives (beta = -0.61, P = 0.001) were associated with lower caregiver burden, whereas formal social support was associated with lower caregiver burden only if it was from family physicians (beta = -0.56, P = 0.001). Compared to caregivers without informal support, those who had one support (beta = -1.62, P < 0.0001) and two or more supports (beta = -1.55, P < 0.0001) had significantly lower burden. This association was not observed for formal support. CONCLUSIONS: Social support from intimate social relationships may positively affect caregivers' psychological wellbeing independent of the receipt of formal social support, resulting in less burden. PMID- 27180935 TI - The FCTC Turns 10: Lessons From the Fist Decade. AB - The Framework Convention on Tobacco Control (FCTC) stands as a landmark approach to addressing a global health problem. It represents the first time the World Health Organization (WHO) used its constitutional right to negotiate an international law and the first time the Member States of WHO agreed to a collective response to chronic, non-communicable diseases. This paper draws lessons from the FCTC's first decade in force and explores what aspects of the FCTC experience can inform future efforts to address other disease epidemics driven by corporate activity, such as alcohol and food. PMID- 27180937 TI - Microbiome: Why you're stuck with the skin you're in. PMID- 27180938 TI - Bacterial pathogenesis: Populations drifting apart. PMID- 27180939 TI - Microbiome: Autophagy genes link OMVs to IBD. PMID- 27180936 TI - Serum bilirubin levels are positively associated with glycemic variability in women with type 2 diabetes. AB - AIMS/INTRODUCTION: Glycemic variability is known to induce oxidative stress. We investigated the relationships between glycemic variability and serum bilirubin levels, an endogenous anti-oxidant, in patients with diabetes. MATERIALS AND METHODS: A cross-sectional study was carried out with 77 patients with type 2 diabetes who had been recruited to two clinical studies from 2008 to 2014. There were no participants with diseases of the pancreas, liver, biliary tract and chronic renal insufficiency. Glycemic variation was calculated by a continuous glucose monitoring system, and correlation analyses were carried out to evaluate their association with bilirubin levels. Multiple linear regression was carried out to identify independent factors influencing bilirubin levels and glycemic variation. RESULTS: Among the participants, 42.3% were men. The mean (standard deviation) age was 61.5 years (10.4 years), body mass index was 24.2 kg/m2 (2.8 kg/m2 ), diabetes duration was 17.7 years (9.5 years), hemoglobin A1c was 60.7 mmol/mol (7.1 mmol/mol; 7.7 [0.7]%) and bilirubin was 11.8 MUmol/L (4.10 MUmol/L). Serum bilirubin levels were not different according to age, body mass index and hemoglobin A1c . However, the mean amplitude of glucose excursion was positively associated with bilirubin levels in women (r = 0.588, P < 0.001). After adjustment with duration of diabetes, serum albumin, liver enzymes, and mean glucose, the correlation between bilirubin and mean amplitude of glucose excursion remained significant (r = 0.566, P < 0.001). Multiple linear regression analyses showed that bilirubin was an independent determinant for the mean amplitude of glucose excursion in women. 1,5-Anhydroglucitol was also associated with bilirubin levels in women. CONCLUSIONS: Bilirubin level within the physiological range might be an independent predictor for glycemic variability in women with type 2 diabetes. PMID- 27180940 TI - Microbiome: Spore formation in the human gut microbiota. PMID- 27180941 TI - Luminescence and luminescence quenching of highly efficient Y2Mo4O15:Eu(3+) phosphors and ceramics. AB - A good LED phosphor must possess strong enough absorption, high quantum yields, colour purity, and quenching temperatures. Our synthesized Y2Mo4O15:Eu(3+) phosphors possess all of these properties. Excitation of these materials with near-UV or blue radiation yields bright red emission and the colour coordinates are relatively stable upon temperature increase. Furthermore, samples doped with 50% Eu(3+) showed quantum yields up to 85%, what is suitable for commercial application. Temperature dependent emission spectra revealed that heavily Eu(3+) doped phosphors possess stable emission up to 400 K and lose half of the efficiency only at 515 K. In addition, ceramic disks of Y2Mo4O15:75%Eu(3+) phosphor with thickness of 0.71 and 0.98 mm were prepared and it turned out that they efficiently convert radiation of 375 and 400 nm LEDs to the red light, whereas combination with 455 nm LED yields purple colour. PMID- 27180942 TI - Neurobiology of HIV-associated neuropsychiatric and neurocognitive disorders. PMID- 27180943 TI - Fabrication of CoTiO3/g-C3N4 Hybrid Photocatalysts with Enhanced H2 Evolution: Z Scheme Photocatalytic Mechanism Insight. AB - A novel direct Z-scheme CoTiO3/g-C3N4 (CT-U) photocatalytic system with different weight percentage of CoTiO3 was synthesized using a facile in situ growth method for H2 evolution from water splitting. The as-prepared CT-U composites composed of 1D CoTiO3 microrod and 2D g-C3N4 nanosheet were characterized by various techniques including XRD, SEM, TEM, XPS, FTIR, and UV-vis. Results demonstrate that the CT-U composite photocatalysts were successfully fabricated, with intimate interfacial contact and heterojunction interaction between g-C3N4 and CoTiO3 which can significantly boost the photocatalytic activity compared with prinstine g-C3N4 and CoTiO3. The most enhanced H2-evolution rate of 858 MUmol h( 1) g(-1) and high quantum efficiency (38.4% at 365 nm, 3.23% at 420 +/- 20 nm) are achieved at an optimal 0.15% CT-U. Meanwhile, the 0.15% CT-U sample exhibits good photocatalytic stability in recycling H2 evolution. Accordingly, direct Z scheme mechanism capable of leading efficient charge carrier separation and strong reduction ability for enhanced H2 production was proposed, and further evidenced by PL, photoelectrochemical analysis, and ESR assay. PMID- 27180944 TI - Let's Face It: Consumer-Focused Technology Is the Future of Cardiovascular Disease Prevention and Treatment. PMID- 27180945 TI - Technology and Public Health: New Tools and Perspectives. PMID- 27180946 TI - Interaction of Skatole and Androstenone in the Olfactory Perception of Boar Taint. AB - This study analyzed odor-odor interactions of two malodorous volatile substances, androstenone and skatole, that may accumulate in fat and meat of uncastrated male (boar) pigs. Therefore, fat samples were collected from 1000+ entire male pig carcasses for sensory evaluation and quantification of boar taint compounds using gas chromatography-mass spectrometry (GC-MS). Each sample was sniffed by 10 trained assessors, resulting in 11 000+ individual ratings, which were subjected to statistical analysis. Pearson correlations of chemical traits and sensory traits (panel average) were higher for skatole [r(1029) = 0.59; p < 0.001] than for androstenone [r(1029) = 0.44; p < 0.001]. Linear terms of androstenone and skatole as well as their interaction significantly (p < 0.05) contributed to perception of deviant smell (R(2) = 0.43). Standardized regression coefficients illustrate the higher importance of skatole (beta = 0.68) than androstenone (beta = 0.39). Interindividual differences in the responses of assessors to androstenone and skatole are confirmed. A new curved approach is suggested because it better accounts for the interaction of androstenone and skatole than the "safe box" approach. On the basis of these data, sorting strategies using instrumental measurements are discussed. An automated detection based on only skatole measurements is recommended because its performance is only slightly inferior to a sorting based on both androstenone and skatole. Sorting thresholds need to be calibrated against consumer acceptance though. PMID- 27180947 TI - The Association between Serum 25-Hydroxy Vitamin D Level and Urine Cathelicidin in Children with a Urinary Tract Infection. AB - OBJECTIVE: Cathelicidin is an important antimicrobial peptide in the urinary tract. Cathelicidin expression is strongly stimulated by 1,25-dihydroxy vitamin D in epithelial cells, macrophages/monocytes, and neutrophils. Vitamin D and cathelicidin status in children with urinary tract infection (UTI) caused by Escherichia coli is unknown. To establish the relationship between serum vitamin D and urine cathelicidin levels in children with a UTI caused by Escherichia coli. METHODS: Serum 25-hydroxy vitamin D and urine cathelicidin levels were measured in 36 patients with UTI (mean age 6.8+/-3.6 years, range: 0.25-12.6 years) and 38 controls (mean age 6.3+/-2.8 years, range: 0.42-13 years). RESULTS: There were no significant differences in urine cathelicidin levels between the study and control groups (p>0.05). Eight (22.2%) patients in the study group and 21 (58.3%) children in the control group were found to have sufficient vitamin D (>=20 ng/mL). Patients with sufficient vitamin D had higher urine cathelicidin levels than the controls with sufficient vitamin D (respectively 262.5+/-41.1 vs. 168+/-31.6 ng/mL, p=0.001). There were no significant differences between the patients and controls with insufficient vitamin D (p>0.05). CONCLUSION: The children with vitamin D insufficiency may not be able to increase their urine cathelicidin level during UTI caused by Escherichia coli. There is a need of prospective studies in order to prove a beneficial effect of vitamin D supplementation for the restoration of cathelicidin stimulation and consequently for prevention of UTI recurrence. PMID- 27180948 TI - Development and Evaluation of a Simulation-based Curriculum for Ultrasound-guided Central Venous Catheterization. AB - OBJECTIVE: To develop a simulation-based curriculum for residents to learn ultrasound-guided (USG) central venous catheter (CVC) insertion, and to study the volume and type of practice that leads to technical proficiency. METHODS: Ten post-graduate year two residents from the Departments of Emergency Medicine and Anesthesiology completed four training sessions of two hours each, at two week intervals, where they engaged in a structured program of deliberate practice of the fundamental skills of USG CVC insertion on a simulator. Progress during training was monitored using regular hand motion analysis (HMA) and performance benchmarks were determined by HMA of local experts. Blinded assessment of video recordings was done at the end of training to assess technical competence using a global rating scale. RESULTS: None of the residents met any of the expert benchmarks at baseline. Over the course of training, the HMA metrics of the residents revealed steady and significant improvement in technical proficiency. By the end of the fourth session six of 10 residents had faster procedure times than the mean expert benchmark, and nine of 10 residents had more efficient left and right hand motions than the mean expert benchmarks. Nine residents achieved mean GRS scores rating them competent to perform independently. CONCLUSION: We successfully developed a simulation-based curriculum for residents learning the skills of USG CVC insertion. Our results suggest that engaging residents in three to four distributed sessions of deliberate practice of the fundamental skills of USG CVC insertion leads to steady and marked improvement in technical proficiency with individuals approaching or exceeding expert level benchmarks. PMID- 27180949 TI - Manual and Instrument Applied Cervical Manipulation for Mechanical Neck Pain: A Randomized Controlled Trial. AB - OBJECTIVE: The purpose of this study was to compare the effects of 2 different cervical manipulation techniques for mechanical neck pain (MNP). METHODS: Participants with MNP of at least 1 month's duration (n = 65) were randomly allocated to 3 groups: (1) stretching (control), (2) stretching plus manually applied manipulation (MAM), and (3) stretching plus instrument-applied manipulation (IAM). MAM consisted of a single high-velocity, low-amplitude cervical chiropractic manipulation, whereas IAM involved the application of a single cervical manipulation using an (Activator IV) adjusting instrument. Preintervention and postintervention measurements were taken of all outcomes measures. Pain was the primary outcome and was measured using visual analogue scale and pressure pain thresholds. Secondary outcomes included cervical range of motion, hand grip-strength, and wrist blood pressure. Follow-up subjective pain scores were obtained via telephone text message 7 days postintervention. RESULTS: Subjective pain scores decreased at 7-day follow-up in the MAM group compared with control (P = .015). Cervical rotation bilaterally (ipsilateral: P = .002; contralateral: P = .015) and lateral flexion on the contralateral side to manipulation (P = .001) increased following MAM. Hand grip-strength on the contralateral side to manipulation (P = .013) increased following IAM. No moderate or severe adverse events were reported. Mild adverse events were reported on 6 occasions (control, 4; MAM, 1; IAM, 1). CONCLUSION: This study demonstrates that a single cervical manipulation is capable of producing immediate and short-term benefits for MNP. The study also demonstrates that not all manipulative techniques have the same effect and that the differences may be mediated by neurological or biomechanical factors inherent to each technique. PMID- 27180950 TI - Prognostic impact of cardiac troponin T in patients with stable coronary artery disease and diabetes. PMID- 27180951 TI - Task modulation of disyllabic spoken word recognition in Mandarin Chinese: a unimodal ERP study. AB - Using unimodal auditory tasks of word-matching and meaning-matching, this study investigated how the phonological and semantic processes in Chinese disyllabic spoken word recognition are modulated by top-down mechanism induced by experimental tasks. Both semantic similarity and word-initial phonological similarity between the primes and targets were manipulated. Results showed that at early stage of recognition (~150-250 ms), an enhanced P2 was elicited by the word-initial phonological mismatch in both tasks. In ~300-500 ms, a fronto central negative component was elicited by word-initial phonological similarities in the word-matching task, while a parietal negativity was elicited by semantically unrelated primes in the meaning-matching task, indicating that both the semantic and phonological processes can be involved in this time window, depending on the task requirements. In the late stage (~500-700 ms), a centro parietal Late N400 was elicited in both tasks, but with a larger effect in the meaning-matching task than in the word-matching task. This finding suggests that the semantic representation of the spoken words can be activated automatically in the late stage of recognition, even when semantic processing is not required. However, the magnitude of the semantic activation is modulated by task requirements. PMID- 27180952 TI - Evaluation of Percutaneous First Annular Pulley Release: Efficacy and Complications in a Perfused Cadaveric Study. AB - PURPOSE: Trigger finger is the most common entrapment tendinopathy, with a lifetime risk of 2% to 3%. Open surgical release of the flexor tendon sheath is a commonly performed procedure associated with a high rate of success. Despite reported success rates of over 94%, percutaneous trigger finger release (PFTR) remains a controversial procedure because of the risk of iatrogenic digital neurovascular injury. This study aimed to evaluate the safety and efficacy of traditional percutaneous and ultrasound (US)-guided first annular (A1) pulley releases performed on a perfused cadaveric model. METHODS: First annular pulley releases were performed percutaneously using an 18-gauge needle in 155 digits (124 fingers and 31 thumbs) of un-embalmed cadavers with restored perfusion. A total of 45 digits were completed with US guidance and 110 digits were completed without it. Each digit was dissected and assessed regarding the amount of release as well as neurovascular, flexor tendon, and A2 pulley injury. RESULTS: Overall, 114 A1 pulleys were completely released (74%). There were 38 partial releases (24%) and 3 complete misses (2%). No significant flexor tendon injury was seen. Longitudinal scoring of the flexor tendon was found in 35 fingers (23%). There were no lacerations to digital nerves and one ulnar digital artery was partially lacerated (1%) in a middle finger with a partial flexion contracture that prevented appropriate hyperextension. The ultrasound-assisted and blind PTFR techniques had similar complete pulley release and injury rates. CONCLUSIONS: Both traditional and US-assisted percutaneous release of the A1 pulley can be performed for all fingers. Perfusion of cadaver digits enhances surgical simulation and evaluation of PTFR beyond those of previous cadaveric studies. The addition of vascular flow to the digits during percutaneous release allows for Doppler flow assessment of the neurovascular bundle and evaluation of vascular injury. CLINICAL RELEVANCE: Our cadaveric data align with those of published clinical investigations for percutaneous A1 pulley release. PMID- 27180953 TI - Pachydermodactyly: A Case Report Including Histopathology. AB - Pachydermodactyly (PDD) is a rare form of digital fibromatosis characterized by painless soft tissue swelling, primarily about the proximal interphalangeal joints. The skin at the metacarpophalangeal joints, the palm, and the dorsum of the hand may also be involved. Because swelling can occur over the proximal interphalangeal and metacarpophalangeal joints, PDD may be confused with juvenile inflammatory arthropathy and may even occur concurrently. We present the clinical and histopathologic findings of a case of PDD characterized by bilateral proximal phalangeal involvement of the index through little fingers. PMID- 27180955 TI - Signaling pathways effecting crosstalk between cartilage and adjacent tissues: Seminars in cell and developmental biology: The biology and pathology of cartilage. AB - Endochondral ossification, the mechanism responsible for the development of the long bones, is dependent on an extremely stringent coordination between the processes of chondrocyte maturation in the growth plate, vascular expansion in the surrounding tissues, and osteoblast differentiation and osteogenesis in the perichondrium and the developing bone center. The synchronization of these processes occurring in adjacent tissues is regulated through vigorous crosstalk between chondrocytes, endothelial cells and osteoblast lineage cells. Our knowledge about the molecular constituents of these bidirectional communications is undoubtedly incomplete, but certainly some signaling pathways effective in cartilage have been recognized to play key roles in steering vascularization and osteogenesis in the perichondrial tissues. These include hypoxia-driven signaling pathways, governed by the hypoxia-inducible factors (HIFs) and vascular endothelial growth factor (VEGF), which are absolutely essential for the survival and functioning of chondrocytes in the avascular growth plate, at least in part by regulating the oxygenation of developing cartilage through the stimulation of angiogenesis in the surrounding tissues. A second coordinating signal emanating from cartilage and regulating developmental processes in the adjacent perichondrium is Indian Hedgehog (IHH). IHH, produced by pre-hypertrophic and early hypertrophic chondrocytes in the growth plate, induces the differentiation of adjacent perichondrial progenitor cells into osteoblasts, thereby harmonizing the site and time of bone formation with the developmental progression of chondrogenesis. Both signaling pathways represent vital mediators of the tightly organized conversion of avascular cartilage into vascularized and mineralized bone during endochondral ossification. PMID- 27180954 TI - Effects of acetyl-L-carnitine and methylcobalamin for diabetic peripheral neuropathy: A multicenter, randomized, double-blind, controlled trial. AB - AIMS/INTRODUCTION: To assess the efficacy and safety of acetyl-L-carnitine (ALC) on diabetic peripheral neuropathy compared with methylcobalamin (MC). MATERIALS AND METHODS: This was a multicenter, randomized, parallel-group, double-blind, double-dummy, positive-controlled, non-inferior phase II clinical trial. Diabetic patients with abnormal nerve conduction test results were randomized in a 1:1 ratio to receive oral ALC 500 mg t.i.d. or MC 0.5 mg t.i.d. for 24 weeks. The neuropathy symptom score, neuropathy disability score and neurophysiological parameters were measured during follow up. RESULTS: A total of 232 patients were randomized (ALC n = 117, MC n = 115), 88% of which completed the trial. At week 24, patients from both groups had significant reductions in both neuropathy symptom score and neuropathy disability score with no significant difference between two groups (neuropathy symptom score reduction: ALC vs MC 2.35 +/- 2.23, P < 0.0001 vs 2.11 +/- 2.48, P < 0.0001, intergroup P = 0.38; neuropathy disability score reduction ALC vs MC 1.66 +/- 1.90, P < 0.0001 vs 1.35 +/- 1.65, P < 0.0001, intergroup P = 0.23). Neurophysiological parameters were also improved in both groups. No significant difference was found between groups in the development of adverse events. CONCLUSIONS: ALC is as effective as MC in improving clinical symptoms and neurophysiological parameters for patients with diabetic peripheral neuropathy over a 24-week period with good tolerance. PMID- 27180956 TI - Chemical nature of alkaline polyphosphate boundary film at heated rubbing surfaces. AB - Alkaline polyphosphate has been demonstrated to be able to reduce significant wear and friction of sliding interfaces under heavy loads (>1 GPa) and elevated temperature (800 degrees C and above) conditions, e.g. hot metal manufacturing. The chemical composition and fine structure of polyphosphate lubricating film is not well understood as well as the role of alkaline elements within the reaction film at hot rubbing surface. This work makes use of the coupling surface analytical techniques on the alkaline polyphosphate tribofilm, XANES, TOF-SIMS and FIB/TEM. The data show the composition in gradient distribution and trilaminar structure of tribofilm: a shorter chain phosphate overlying a long chain polyphosphate that adheres onto oxide steel base through a short chain phosphate. The chemical hardness model well explains the anti-abrasive mechanism of alkaline polyphosphate at elevated temperatures and also predicts a depolymerisation and simultaneous cross-linking of the polyphosphate glass. The role of alkaline elements in the lubrication mechanism is especially explained. This work firstly serves as a basis for a detailed study of alkaline polyphosphate tribofilm at temperature over 600 degrees C. PMID- 27180957 TI - The percentage of iNKT cells among other immune cells at various clinical stages of laryngeal cancer. AB - INTRODUCTION: Invariant natural killer T (iNKT) cells constitute a small population of immune cells that share functional and phenotypic characteristics of T lymphocytes and NK cells. Due to their involvement in specific and non specific immune responses, iNKT cells may represent an important component of antitumor and anti-infectious immunity. MATERIAL AND METHODS: Using flow cytometry, we analyzed the percentages of iNKT cells as well as T and B lymphocytes in peripheral blood of 50 laryngeal cancer patients at various clinical stages in comparison to healthy controls (n=15). Moreover, we determined the expression of CD25, CD69 and CD95 antigens on T lymphocytes. RESULTS: The percentage of CD4+/CD3+ T lymphocytes in the controls was higher than in laryngeal cancer patients, both with early and late stages of the disease. The percentage of CD8+/CD3+ T lymphocytes in healthy controls was lower than in patients with early and late clinical stages of laryngeal cancer. Patients with advanced laryngeal cancer showed a lower percentage of iNKT cells and higher frequencies of T regulatory cells (Tregs) than the controls. Advanced clinical stages of laryngeal cancer are associated with impaired activation of lymphocytes. CONCLUSIONS: Our study confirmed that laryngeal cancer cells exert a strong suppressor effect on the immune system of the host. This is reflected by a decrease in the percentage of iNKT cells that are capable of cancer cell elimination, and a concomitant increase in the percentage of Tregs. However, further studies are needed in order to explain the underlying mechanisms of immunosuppression and understand interactions between immune and cancer cells. PMID- 27180958 TI - [The use of oligonucleotide aptamers in cancer therapy]. AB - Aptamers are a new class of molecules which originated in the 1990s. They are usually RNA or DNA oligonucleotides, the length of which ranges between 20 and 80 nt. They are produced using the SELEX method that allows one to obtain aptamers that bind to virtually any molecule of interest, providing a high specificity. Aptamers are an alternative to antibodies because on the one hand, their sensitivity is at a similar or sometimes even higher level, while on the other hand they do not show immunogenicity, and may be synthesized in vitro. To date, a broad range of different applications of aptamers has been described: as components of biosensors, or use in various laboratory techniques, such as microarrays or chromatography. One of the most important is the use of aptamers in medicine, especially in the fight against cancer. They can be used both for diagnosis and for the eradication of cancers - particularly through the delivery of drugs. Currently, most transport-related research is devoted to the delivery of chemotherapeutic drugs, such as doxorubicin. This was used in research on liver cancer cells, prostate, and acute lymphoblastic leukemia blast cells. Another possibility is to use aptamers to deliver siRNAs. In this way inhibition of the quality control process of the mRNA in tumor cells is possible. An aptamer complex with the drug allows for direct delivery of the active substance in a particular cell type, substantially eliminating the non-specific effect of the drug. PMID- 27180959 TI - [Juvenile idiopathic arthritis and oral health]. AB - Juvenile idiopathic arthritis (JIA) is the most common autoimmune inflammatory disease of connective tissue in children. It is characterized by progressive joint destruction which causes preserved changes in the musculoskeletal system. The literature describes fully clinical symptoms and radiological images in different subtypes of JIA. However, there is still a limited number of studies reporting on the medical condition of the oral cavity of ill children. JIA can affect hard and soft tissues of the oral cavity by: the general condition of the child's health, arthritis of the upper limbs, as the result of the pharmacotherapy, changes in secretion and composition of saliva, inflammation of the temporomandibular joint and facial deformity. The study summarizes the available literature on the condition of the teeth and periodontal and oral hygiene in the course of JIA. The presence of diverse factors that modify the oral cavity, such as facial growth, functioning of salivary glands, or the supervision and care provided by adults, prevents clear identification if JIA leads to severe dental caries and periodontal disease. Despite conflicting results in studies concerning the clinical oral status, individuals with JIA require special attention regarding disease prevention and maintenance of oral health. PMID- 27180960 TI - Case control study of ANKK1 Taq 1A polymorphism in patients with alcohol dependence classified according to Lesch's typology. AB - OBJECTIVE: The aim of this study was to examine the association between the Taq 1A polymorphism of the ANKK1 gene in homogeneous subgroups of patients with alcohol dependence syndrome divided according to Lesch's typology. MATERIAL/METHODS: DNA was provided from alcohol-dependent (AD) patients (n = 373) and healthy control subjects (n = 168), all of Polish descent. The history of alcoholism was obtained using the Polish version of the SSAGA (Semi-Structured Assessment for the Genetics of Alcoholism). Samples were genotyped using the PCR method. RESULTS: We found no association between alcohol dependence and ANKK1 Taq 1A polymorphism. CONCLUSIONS: Lesch's typology is a clinical consequence of the disease, and its phenotypic description is too complex for simple genetic analysis. PMID- 27180961 TI - [Drugs affecting the incretin system and renal glucose transport: do they meet the expectations of modern therapy of type 2 diabetes?]. AB - Agents introduced into therapy of type 2 diabetes in the last few years are still the subject of numerous clinical and experimental studies. Although many studies have been completed, we still do not know all aspects of these drugs' action, especially the long-term effects of their use. Most questionable is their impact on the processes of cell proliferation, on the cardiovascular and immune systems, on lipids and uric acid metabolism. A summary of the most important observations on the use of three groups of new drugs - analogs of glucagon-like peptide 1 (GLP 1), inhibitors of dipeptidyl peptidase IV (DPPIV) and inhibitors of sodium glucose cotransporters (SGLT1 and SGLT2) - has been made, based on a review of the literature over the past five years (2010-2014). The information included in the present review concerns the structure and activity relationship, therapeutic efficacy, side effects and the observed additional therapeutic effects, which can determine new standards in therapy of diabetes and also facilitate the development of better antidiabetic drugs. PMID- 27180962 TI - Association between selected gene polymorphisms and statin metabolism, risk of ischemic stroke and cardiovascular disorders. AB - Statins are increasingly widely used in primary and secondary prevention of cardiovascular disorders, including ischemic stroke. The initial studies regarded mainly coronary heart disease, but recently more attention has been paid to statin use in ischemic stroke, including primary and secondary prevention as well as the acute phase treatment. Besides their main hypolipemic activity, statins have been proved to have immunomodulating properties that are called a pleiotropic effect. Drug metabolism is under genetic influence, exemplified by the single nucleotide polymorphisms (SNPs). This also applies to statins. Pharmacogenetic studies are conducted in many disorders including stroke. The aim of this study was to review selected common genetic variants in lipid or statin metabolism-related genes and indicate associations with cardiovascular disorders, especially with ischemic stroke. We present available data of SNPs in regard to the most significant and promising proteins such as cytochrome P450, ATPase superfamily, organic anion transporter family, apolipoprotein E, lipoprotein associated phospholipase A2, lipoprotein(a), LDLR, proprotein convertase subtilisin/kexin type 9, HMGCR, and CETP. A presentation of particular SNPs may help in future studies to aim for individual and thus more effective statin therapy in stroke patients. PMID- 27180963 TI - [Significance of increased and reduced proteasome activity in the pathomechanism of selected disorders]. AB - Proteasomes are structures responsible for the elimination of damaged and misfolded proteins. Thus, they also regulate the most important intracellular processes. Changes in their functions can lead to many molecular diseases. There are two possible disorders in the function of proteasomes. Their increasing activity causes excessive degradation of important cell proteins. On the other hand, their insufficiency can inhibit the degradation of pathological proteins and lead to their accumulation. The increase of proteasome activity and the degradation of important proteins are observed in many pathological disorders. Therefore the study of pharmacological methods using proteasome inhibitors has gained growing interest in the last years. This review summarizes recent findings regarding the role of proteasomes in pathogenesis of selected diseases and discusses the potential use of proteasomes in diagnosis of different disorders. PMID- 27180964 TI - [Treatment of nephrotic syndrome: immuno- or rather podocyte therapy?]. AB - Nephrotic syndrome (NS) is a group of clinical symptoms resulting from massive proteinuria caused by impairment of the glomerular filtration barrier. The filtration barrier comprises glomerular basement membrane with endothelial cells lining its inner side and a podocyte monolayer covering its outer aspect. As well as forming part of the glomerular filter, podocytes also regulate synthesis of other components of the filtration barrier. Therefore, integrity of these cells is crucial for maintaining the normal ultrafiltration function. The pathogenesis of idiopathic nephrotic syndrome (INS) was proposed to be associated with autoimmunity and appearance in the circulation of a still unknown protein permeability factor (PF) inducing changes in the glomerular filtration barrier. Several candidate PFs have been identified to date, and current results indicate that podocytes are target cells for all of them. Changes in podocyte structure and functions induced by these factors are typical for changes observed in patients with nephrotic proteinuria. Most pharmacotherapeutic approaches in NS are based on various immunosuppressive agents and are targeted toward minimizing proteinuria. It appears, however, that these drugs not only target the cells of the immune system but also act directly on podocytes. Thus, it can be concluded that detailed studies on mechanisms regulating podocyte functions as well as designing drugs to protect these cells are required for effective therapy of NS. PMID- 27180965 TI - [BRAF mutation in progression and therapy of melanoma, papillary thyroid carcinoma and colorectal adenocarcinoma]. AB - BRAF is mutated at a high frequency in various malignancies, including melanoma, papillary thyroid carcinoma and colorectal adenocarcinoma. BRAF is an element of the RAS/RAF/MEK/ERK (MAPK) pathway, which when constitutively active can lead to increased proliferation rate, enhanced survival, invasion and metastasis. The development of small molecule inhibitors of mutant BRAF kinase has changed the care of patients, especially with melanoma. Despite the success in treating melanoma with inhibitors of mutant BRAF and other elements of RAS/RAF/MEK/ERK (MAPK) pathway, resistance limits the long-term responsiveness to these drugs. The resistance mechanisms to MAPK pathway inhibition are complex, occur at genomic and phenotypic levels, and frequently the same patient can simultaneously develop diverse mechanisms of resistance in different progressive metastases or even in the same lesion. In the current review, we summarize recent research on mutations in BRAF and their importance for the development of tumor. This review will also give an overview on the current knowledge concerning therapies for patients harboring mutation in BRAF and discusses the diverse mechanisms of resistance developed in response to these targeted therapies. PMID- 27180966 TI - [The biological role of sulfatides]. AB - Sulfatides (3-O-sulfogalactosylceramides, sulfated galactocerebrosides, SM4) are esters of sulfuric acid with galactosylceramides. These acidic glycosphingolipids, present at the external leaflet of the plasma membrane, are synthesized by a variety of mammalian cells. They are especially abundant in the myelin sheath of oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system. Studies using cerebroside galactosyltransferase deficient mice revealed that sulfatides are responsible for proper structure and functioning of myelin. Large amounts of sulfatides are also found in the kidney, gastrointestinal tract, islets of Langerhans, and membranes of erythrocytes, thrombocytes and granulocytes. They are ligands for numerous proteins, but in most cases the biological role of such interactions is poorly understood. A notable exception is their binding by P- and L-selectins. Platelet sulfatides are major ligands for P-selectin, and this interaction is critical for the formation of stable platelet aggregates. Sulfatides also bind to chemokines, and seem to play a role in regulation of cytokine expression in human lymphocytes and monocytes. Aberrant metabolism of sulfatides, could cause several important human diseases. In this article, we describe the changes in sulfatide expression associated with such nervous disorders as metachromatic leukodystrophy (MLD), Parkinson's disease and Alzheimer's disease, and several types of cancer, e.g. colon cancer, kidney cancer, and ovarian cancer. We also discuss the involvement of sulfatides in cancer progression, diabetes and autoimmune and immune disorders such as multiple sclerosis. This acidic glycosphingolipids seem to play an important role in pathogenesis of infectious diseases, serving as receptors for binding various bacteria and viruses. PMID- 27180967 TI - Analysis of Clostridium difficile infections in patients hospitalized at the nephrological ward in Poland. AB - BACKGROUND: Few studies have evaluated the incidence and risk factors of Clostridium difficile infection (CDI) in the adult Polish population, in particular in solid organ recipients hospitalized at the nephrological ward. AIM: The aim of this study was to analyze Clostridium difficile infections (CDI) among patients hospitalized in the Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia in Katowice. MATERIAL/METHODS: Thirty-seven patients with Clostridium difficile infection diagnosed between October 2011 and November 2013 (26 months), identified among a total of 3728 patients hospitalized in this department during this period, were included in this retrospective, single-center study. The CDI definition was based on the current recommendations of the European Society of Clinical Microbiology and Infectious Diseases. RESULTS: The observation period was divided into two 13 month intervals. Increased incidence (of borderline significance) of CDI in the second period compared to the first period was observed (1.33% vs 0.65% respectively; p=0.057). Patients after kidney (n=11), kidney and pancreas (n=2) and liver (n=5) transplantation represented 48% of the analyzed CDI patients, and in half of these patients (50%) CDI symptoms occurred within the first 3 months after transplantation. Clostridium difficile infection leads to irreversible deterioration of graft function in 38% of kidney recipients. Most incidents of CDI (70%) were identified as nosocomial infection. CONCLUSIONS: 1. Clostridium difficile infection is particularly common among patients in the early period after solid organ transplantation. 2. Clostridium difficile infection may lead to irreversible deterioration of transplanted kidney function. PMID- 27180968 TI - [Carbamylation of proteins--mechanism, causes and consequences]. AB - Carbamylation (carbamoylation) is a post-translational modification resulting from the nonenzymatic reaction between isocyanic acid and free functional groups of proteins, in particular with the free amino groups. This reaction alters structural and functional properties of proteins and results in faster aging of proteins. Urea present in the body can be transformed into cyanate and its more reactive form, isocyanic acid. High concentration of urea is associated with some diseases, especially with chronic renal failure and atherosclerosis. In human tissues, urea and cyanate are in equilibrium in aqueous solutions. Surprisingly, concentration of isocyanate in the body is much lower than it would appear from the kinetic parameters of urea decomposition. The low concentration of isocyanic acid results from its high reactivity and short half-life. In this review we describe the biochemical mechanism of carbamylation of proteins and free amino acids. We summarize the literature data for carbamylation of hemoglobin, lipoproteins, albumin, membrane proteins and erythropoietin in chronic renal failure. In summary, the carbamylation of proteins may have a negative impact on their biological activity and may contribute to the deterioration of patients with chronic renal failure. PMID- 27180969 TI - Comparable pharmacodynamics, efficacy, and safety of linagliptin 5 mg among Japanese, Asian and white patients with type 2 diabetes. AB - AIMS/INTRODUCTION: The efficacy and safety of drugs can vary between different races or ethnic populations because of differences in the relationship of dose to exposure, pharmacodynamic response or clinical efficacy and safety. In the present post-hoc analysis, we assessed the influence of race on the pharmacokinetics, pharmacodynamics, efficacy and safety of monotherapy with the dipeptidyl peptidase-4 inhibitor, linagliptin, in patients with type 2 diabetes enrolled in two comparable, previously reported randomized phase III trials. MATERIALS AND METHODS: Study 1 (with a 12-week placebo-controlled phase) recruited Japanese patients only (linagliptin, n = 159; placebo, n = 80); study 2 (24-week trial) enrolled Asian (non-Japanese; linagliptin, n = 156; placebo, n = 76) and white patients (linagliptin, n = 180; placebo, n = 90). RESULTS: Linagliptin trough concentrations were equivalent across study and race groups, and were higher than half-maximal inhibitory concentration, resulting in dipeptidyl peptidase-4 inhibition >80% at trough. Linagliptin inhibited plasma dipeptidyl peptidase-4 activity to a similar degree in study 1 and study 2. Linagliptin reduced fasting plasma glucose concentrations by a similar magnitude across groups, leading to clinically relevant reductions in glycated hemoglobin in all groups. Glycated hemoglobin levels decreased to a slightly greater extent in study 1 (Japanese) and in Asian (non-Japanese) patients from study 2. Linagliptin had a favorable safety profile in each race group. CONCLUSIONS: Trough exposure, pharmacodynamic response, and efficacy and safety of linagliptin monotherapy were comparable among Japanese, Asian (non-Japanese) and white patients, confirming that the recommended 5-mg once-daily dose of linagliptin is appropriate for use among different race groups. PMID- 27180970 TI - Is ghrelin a glucagon-like peptide-1 secretagogue? AB - Ghrelin was reported to enhance GLP-1 secretion after glucose load in mice. PMID- 27180971 TI - Phosphoprotein network analysis of white adipose tissues unveils deregulated pathways in response to high-fat diet. AB - Despite efforts in the last decade, signaling aberrations associated with obesity remain poorly understood. To dissect molecular mechanisms that define this complex metabolic disorder, we carried out global phosphoproteomic analysis of white adipose tissue (WAT) from mice fed on low-fat diet (LFD) and high-fat diet (HFD). We quantified phosphorylation levels on 7696 peptides, and found significant differential phosphorylation levels in 282 phosphosites from 191 proteins, including various insulin-responsive proteins and metabolic enzymes involved in lipid homeostasis in response to high-fat feeding. Kinase-substrate prediction and integrated network analysis of the altered phosphoproteins revealed underlying signaling modulations during HFD-induced obesity, and suggested deregulation of lipogenic and lipolytic pathways. Mutation of the differentially-regulated novel phosphosite on cytoplasmic acetyl-coA forming enzyme ACSS2 (S263A) upon HFD-induced obesity led to accumulation of serum triglycerides and reduced insulin-responsive AKT phosphorylation as compared to wild type ACSS2, thus highlighting its role in obesity. Altogether, our study presents a comprehensive map of adipose tissue phosphoproteome in obesity and reveals many previously unknown candidate phosphorylation sites for future functional investigation. PMID- 27180972 TI - Smart Nanotransformers with Unique Enzyme-Inducible Structural Changes and Drug Release Properties. AB - We previously reported a high aspect ratio peptide nanofiber that could be effectively delivered to tumors with minimal nonspecific uptake by other organs. The peptidic nature offers the design flexibility of smart formulation with unique responsiveness. Two new formulations that behave congruously as nanotransformers (NTFs) are reported herein. NTF1 and NTF2 could biomechanically remodel upon enzyme activation to generate a degradable and an aggregable effect, respectively, within the lysosomal compartment. These NTFs were further evaluated as carriers of mertansine (DM1), a microtubule inhibitor. DM1-loaded NTF1 could be degraded by cathepsin B (CathB) to release the same active metabolite, as previously described in the lysosomal degradation of antibody-DM1 conjugate. In contrast, CathB only partially digested DM1-loaded NTF2 and induced aggregate formation to become a storage reservoir with slow payload release property. The DM1-loaded NTF1 exhibited a comparable cytotoxicity to the free drug and was more effective than the NTF2 formulation in eradicating triple negative breast cancer. Our data suggested that biological transformers with distinct enzyme-induced structural changes and payload release profiles could be designed for the intracellular delivery of cytotoxic and imaging agents. PMID- 27180973 TI - Resistant Shigella strains in refugees, August-October 2015, Greece. AB - Shigellosis is endemic in most developing countries and thus a known risk in refugees and internally displaced persons. In 2015, a massive influx of refugees into Greece, due to the political crisis in the Middle East, led to the development of appropriate conditions for outbreaks of communicable diseases as shigellosis. We present a cluster of 16 shigellosis cases in refugees, detected by the implementation of a syndromic notification system in one transit centre in Athens, between 20 August and 7 October 2015. Both Shigella flexneri (n = 8) and S. sonnei (n = 8) were identified, distributed in various serotypes. All tested isolates (n = 13) were multidrug resistant; seven were CTX-M-type extended spectrum beta-lactamase producers. Our results indicate lack of a potential common source, although pulsed-field gel electrophoresis typing results revealed small clusters in isolates of the same serotype indicating possible limited person-to-person transmission without identifying secondary community cases related to the refugees. To prevent the spread of shigellosis, empirical antibiotic treatment as well as environmental hygiene measures were implemented. The detection of multi-drug resistance is important for determining the appropriate empirical antibiotic treatment for the more severe cases, while at the same time real-time typing is useful for epidemiological investigation and control measures. PMID- 27180974 TI - Pneumocystis jirovecii pneumonia developed in a patient with rheumatoid arthritis after 14 weeks of iguratimod add-on to treatment with methotrexate and etanercept. AB - A 66-year-old woman who had rheumatoid arthritis and underwent a long-term treatment with methotrexate and etanercept developed Pneumocystis jirovecii pneumonia (PCP) 3 months after iguratimod add-on. Although most rheumatologists might have the impression that iguratimod has less toxicity and immunosuppressive effect compared with methotrexate and biologic disease-modifying antirheumatic drugs, this case suggests that iguratimod may increase the risk of PCP, especially in combination with other drugs. PMID- 27180975 TI - Absorption, distribution, metabolism and excretion (ADME) of the ALK inhibitor alectinib: results from an absolute bioavailability and mass balance study in healthy subjects. AB - 1. Alectinib is a highly selective, central nervous system-active small molecule anaplastic lymphoma kinase inhibitor. 2. The absolute bioavailability, metabolism, excretion and pharmacokinetics of alectinib were studied in a two period single-sequence crossover study. A 50 MUg radiolabelled intravenous microdose of alectinib was co-administered with a single 600 mg oral dose of alectinib in the first period, and a single 600 mg/67 MUCi oral dose of radiolabelled alectinib was administered in the second period to six healthy male subjects. 3. The absolute bioavailability of alectinib was moderate at 36.9%. Geometric mean clearance was 34.5 L/h, volume of distribution was 475 L and the hepatic extraction ratio was low (0.14). 4. Near-complete recovery of administered radioactivity was achieved within 168 h post-dose (98.2%) with excretion predominantly in faeces (97.8%) and negligible excretion in urine (0.456%). Alectinib and its major active metabolite, M4, were the main components in plasma, accounting for 76% of total plasma radioactivity. In faeces, 84% of dose was excreted as unchanged alectinib with metabolites M4, M1a/b and M6 contributing to 5.8%, 7.2% and 0.2% of dose, respectively. 5. This novel study design characterised the full absorption, distribution, metabolism and excretion properties in each subject, providing insight into alectinib absorption and disposition in humans. PMID- 27180976 TI - Detection of the European epidemic strain of Trichomonas gallinae in finches, but not other non-columbiformes, in the absence of macroscopic disease. AB - Finch trichomonosis is an emerging infectious disease affecting European passerines caused by a clonal strain of Trichomonas gallinae. Migrating chaffinches (Fringilla coelebs) were proposed as the likely vector of parasite spread from Great Britain to Fennoscandia. To test for such parasite carriage, we screened samples of oesophagus/crop from 275 Apodiform, Passeriform and Piciform birds (40 species) which had no macroscopic evidence of trichomonosis (i.e. necrotic ingluvitis). These birds were found dead following the emergence of trichomonosis in Great Britain, 2009-2012, and were examined post-mortem. Polymerase chain reactions were used to detect (ITS1/5.8S rRNA/ITS2 region and single subunit rRNA gene) and to subtype (Fe-hydrogenase gene) T. gallinae. Trichomonas gallinae was detected in six finches [three chaffinches, two greenfinches (Chloris chloris) and a bullfinch (Pyrrhula pyrrhula)]. Sequence data had 100% identity to the European finch epidemic A1 strain for each species. While these results are consistent with finches being vectors of T. gallinae, alternative explanations include the presence of incubating or resolved T. gallinae infections. The inclusion of histopathological examination would help elucidate the significance of T. gallinae infection in the absence of macroscopic lesions. PMID- 27180978 TI - Unconjugated bilirubin elevation impairs the function and expression of breast cancer resistance protein (BCRP) at the blood-brain barrier in bile duct-ligated rats. AB - AIM: Liver failure is associated with dyshomeostasis of efflux transporters at the blood-brain barrier (BBB), which contributes to hepatic encephalopathy. In this study we examined whether breast cancer resistance protein (BCRP), a major efflux transporter at the BBB, was altered during liver failure in rats. METHODS: Rats underwent bile duct ligation (BDL) surgery, and then were sacrificed after intravenous injection of prazosin on d3, d7 and d14. The brains and blood samples were collected. BCRP function at the BBB was assessed by the brain-to-plasma prazosin concentration ratio; Evans Blue extravasation in the brain tissues was used as an indicator of BBB integrity. The protein levels of BCRP in the brain tissues were detected. Human cerebral microvessel endothelial cells (HCMEC/D3) and Madin-Darby canine kidney cells expressing human BCRP (MDCK-BCRP) were tested in vitro. In addition, hyperbilirubinemia (HB) was induced in rats by intravenous injection of unconjugated bilirubin (UCB). RESULTS: BDL rats exhibited progressive decline of liver function and HB from d3 to d14. In the brain tissues of BDL rats, both the function and protein levels of BCRP were progressively decreased, whereas the BBB integrity was intact. Furthermore, BDL rat serum significantly decreased BCRP function and protein levels in HCMEC/D3 cells. Among the abnormally altered components in BDL rat serum tested, UCB (10, 25 MUmol/L) dose-dependently inhibit BCRP function and protein levels in HCMEC/D3 cells, whereas 3 bile acids (CDCA, UDCA and DCA) had no effect. Similar results were obtained in MDCK-BCRP cells and in the brains of HB rats. Correlation analysis revealed that UCB levels were negatively correlated with BCRP expression in the brain tissues of BDL rats and HB rats as well as in two types of cells tested in vitro. CONCLUSION: UCB elevation in BDL rats impairs the function and expression of BCRP at the BBB, thus contributing to hepatic encephalopathy. PMID- 27180979 TI - Ciprofloxacin blocked enterohepatic circulation of diclofenac and alleviated NSAID-induced enteropathy in rats partly by inhibiting intestinal beta glucuronidase activity. AB - AIM: Diclofenac is a non-steroidal anti-inflammatory drug (NSAID), which may cause serious intestinal adverse reactions (enteropathy). In this study we investigated whether co-administration of ciprofloxacin affected the pharmacokinetics of diclofenac and diclofenac-induced enteropathy in rats. METHODS: The pharmacokinetics of diclofenac was assessed in rats after receiving diclofenac (10 mg/kg, ig, or 5 mg/kg, iv), with or without ciprofloxacin (20 mg/kg, ig) co-administered. After receiving 6 oral doses or 15 intravenous doses of diclofenac, the rats were sacrificed, and small intestine was removed to examine diclofenac-induced enteropathy. beta-Glucuronidase activity in intestinal content, bovine liver and E coli was evaluated. RESULTS: Following oral or intravenous administration, the pharmacokinetic profile of diclofenac displayed typical enterohepatic circulation, and co-administration of ciprofloxacin abolished the enterohepatic circulation, resulted in significant reduction in the plasma content of diclofenac. In control rats, beta-glucuronidase activity in small intestinal content was region-dependent: proximal intestine S1 electronic transition in 1H-Py(+), and a band origin was used at 20580.96 cm(-1). The displaced harmonic oscillator approximation and Franck-Condon approximation were used to simulate the absorption spectrum of the (1) (1)A' <- X[combining tilde](1)A' transition of 1H-Py(+), and the main vibronic transitions were assigned for the first pipi* state. It shows that the vibronic structures were dominated by one of the eight active totally symmetric modes, with nu15 being the most crucial. This indicates that the electronic transition of the S1((1)A') state calculated in the adiabatic representation effectively includes a contribution from the adiabatic vibronic coupling through Franck-Condon factors perturbed by harmonic oscillators. The present method can adequately reproduce experimental absorption and fluorescence spectra of a gas phase. PMID- 27181018 TI - Clinicopathologic characteristics and prognostic of gastric cancer in young patients. AB - OBJECTIVES: Gastric cancer (GC) in young patients is thought to exhibit a worse prognosis due to specific clinicopathologic characteristics and delayed diagnosis; however, the data are controversial. This study aimed to analyse the clinicopathologic characteristics and prognostic factors of GC in young patients and to determine whether GC is a different clinical entity in younger vs. older patients. PATIENTS AND METHODS: Clinical data of 3930 gastric cancer patients who underwent radical gastrectomy were retrospectively analysed and divided into two age groups. The younger group consisted of 342 cases of patients aged 40 years or younger at the time of surgery, and the older group included 3588 cases of patients older than 40 years. Clinicopathologic characteristics were compared using Pearson's chi(2) or Fisher's exact tests, and survival curves were constructed using the Kaplan-Meier method. RESULTS: Clinicopathologic characteristics of the younger group exhibited a predominance of females (p < 0.001), diffuse stomach lesions (p = 0.014), signet-ring cell type (p < 0.001), poorly differentiated histological tumours (p < 0.001), Borrmann type IV (p < 0.001), mixed Lauren's classification types (p = 0.004), and recurrence rate in the gastric remnant (p < 0.001). The overall 5-year survival rates in the younger group and older group were 60.8% and 53.7%, respectively (p = 0.017). When stratified by TNM stage, the younger group exhibited enhanced 5-year survival at stage IV compared with the older group (26.9% VS. 10.3%, p = 0.003). CONCLUSION: Although younger patients with GC exhibit more aggressive cancer patterns and higher recurrence rate in the gastric remnant, the overall 5-year survival rate may be better than older patients. PMID- 27181020 TI - Patterning of Metal Films on Arbitrary Substrates by Using Polydopamine as a UV Sensitive Catalytic Layer for Electroless Deposition. AB - Patterning metal films on various substrates is essentially important and yet challenging for developing a wide variety of innovative devices. We herein report a versatile approach to pattern metal (gold, silver, or copper) films on arbitrary substrates by using the bio-inspired polydopamine (PDA) thin film as a UV-sensitive adhesive layer for electroless deposition. The PDA film is able to be formed on virtually any solid surfaces under mild condition, and its rich catechol groups allow for electroless deposition of metal films with high adhesion stability. Upon UV irradiation, spatially selective oxidation of PDA film occurs and the local metal deposition is inhibited, thus facilitating successful patterning of metal films. Considering its versatility and simplicity, this strategy may demonstrate great applications in manufacturing various innovative devices. PMID- 27181019 TI - Long-term Follow-up Data from Pivotal Studies of Adjuvant Trastuzumab in Early Breast Cancer. AB - The addition of adjuvant trastuzumab therapy for 1 year to standard chemotherapy significantly improved disease-free survival and overall survival versus chemotherapy alone in a number of pivotal early breast cancer studies. Here we review long-term follow-up data on the efficacy, cardiac safety, and general safety of trastuzumab in these pivotal studies. We also evaluate ongoing phase II/III adjuvant trials with newer HER2-targeted agents and the efficacy and safety of the recently developed subcutaneous (SC) formulation of trastuzumab in early breast cancer. Long-term follow-up data confirm the significant survival benefit afforded by the addition of trastuzumab to chemotherapy in patients with HER2-positive disease, with an acceptable safety profile. Long-term cardiac safety data suggest that the incidence of cardiac adverse events is maintained at a relatively low level with continued follow-up. At this present time, 1 year of trastuzumab treatment remains the standard of care in HER2-positive early breast cancer. Future adjuvant trastuzumab treatment strategies should focus on reducing cardiotoxicity, particularly in elderly patients, by identifying potential predictive biomarkers of cardiac dysfunction. Clinicians must also decide whether to omit trastuzumab in women who would achieve little benefit from treatment to avoid cardiotoxicity. PMID- 27181021 TI - Hollow CoP nanopaticle/N-doped graphene hybrids as highly active and stable bifunctional catalysts for full water splitting. AB - An alkaline electrolyzer fabricated by employing hollow CoP nanoparticles/N-doped graphene as bifunctional catalysts exhibits remarkable activity with a current density of 10 mA cm(-2) at a cell voltage of 1.58 V and considerable stability over 65 h of continuous electrolysis operation, favorably comparable to the integrated performance of commercial Pt/C and IrO2. PMID- 27181022 TI - A direct and vicinal functionalization of the 1-methyl-2-quinolone framework: 4 alkoxylation and 3-chlorination. AB - Bis(functionalization), 4-alkoxylation and 3-chlorination, of the 1-methyl-2 quinolone framework was achieved under mild conditions by a sequential treatment of 3-nitrated 1-methyl-2-quinolones with sodium alkoxide and N-chlorosuccinimide. Moreover, a succinimide group instead of an alkoxy group was introduced at the 4 position, affording a masked form of the 4-amino-3-chloro-2-quinolone derivative. Furthermore, the prepared vicinally functionalized quinolones thus obtained were subjected to a Suzuki-Miyaura coupling reaction, arylating the 3-position. PMID- 27181023 TI - Designing for selectivity: weak interactions and the competition for reactive sites on gold catalysts. AB - A major challenge in heterogeneous catalysis is controlling reaction selectivity, especially in complex environments. When more than one species is present in the gas mixture, the competition for binding sites on the surface of a catalyst is an important factor in determining reaction selectivity and activity. We establish an experimental hierarchy for the binding of a series of reaction intermediates on Au(111) and demonstrate that this hierarchy accounts for reaction selectivity on both the single crystal surface and under operating catalytic conditions at atmospheric pressure using a nanoporous Au catalyst. A partial set of measurements of relative binding has been measured by others on other catalyst materials, including Ag, Pd and metal oxide surfaces; a comparison demonstrates the generality of this concept and identifies differences in the trends. Theoretical calculations for a subset of reactants on Au(111) show that weak van der Waals interactions are key to predicting the hierarchy of binding strengths for alkoxides bound to Au(111). This hierarchy is key to the control of the selectivity for partial oxidation of alcohols to esters on both Au surfaces and under working catalytic conditions using nanoporous gold. The selectivity depends on the competition for active sites among key intermediates. New results probing the effect of fluorine substitution are also presented to extend the relation of reaction selectivity to the hierarchy of binding. Motivated by an interest in synthetic manipulation of fluorinated organics, we specifically investigated the influence of the -CF3 group on alcohol reactivity and selectivity. 2,2,2 Trifluoroethanol couples on O-covered Au(111) to yield CF3CH2O-C([double bond, length as m-dash]O)(CF3), but in the presence of methanol or ethanol it preferentially forms the respective 2,2,2-trifluoroethoxy-esters. The ester is not the dominant product in any of these cases, though, indicating that the rate of beta-H elimination from adsorbed trifluoroethoxy is slower than that for either adsorbed methoxy or ethoxy, consistent with their relative estimated beta C-H bond strengths. The measured equilibrium constants for the competition for binding to the surface are 2.9 and 0.38 for ethanol and methanol, respectively, vs. 2,2,2-trifluoroethanol, indicating that the binding strength of 2,2,2 trifluoroethoxy is weaker than ethoxy, but stronger than methoxy. These results are consistent with weakening of the interactions between the surface and the alkyl group due to Pauli repulsion of the electron-rich CF3 group from the surface, which offsets the van der Waals attraction. These experiments provide guiding principles for understanding the effect of fluorination on heterogeneous synthesis and further demonstrate the key role of molecular structure in determining reaction selectivity. PMID- 27181024 TI - Visible-light photoredox synthesis of internal alkynes containing quaternary carbons. AB - A novel and efficient visible-light photoredox method for the synthesis of internal alkynes containing quaternary carbons has been developed via coupling reactions of N-phthalimidoyl oxalates of tert-alcohols with 1-(2 (arylsulfonyl)ethynyl)benzenes. The reactions proceeded well at room temperature with good functional group tolerability. PMID- 27181026 TI - Synergistic effects in ambiphilic phosphino-borane catalysts for the hydroboration of CO2. AB - The benefit of combining both a Lewis acid and a Lewis base in a catalytic system has been established for the hydroboration of CO2, using ferrocene-based phosphine, borane and phosphino-borane derivatives. PMID- 27181025 TI - Tissue Plasminogen Activator Neurotoxicity is Neutralized by Recombinant ADAMTS 13. AB - Tissue plasminogen activator (tPA) is an effective treatment for ischemic stroke, but its neurotoxicity is a significant problem. Here we tested the hypothesis that recombinant ADAMTS 13 (rADAMTS 13) would reduce tPA neurotoxicity in a mouse model of stroke. We show that treatment with rADAMTS 13 in combination with tPA significantly reduced infarct volume compared with mice treated with tPA alone 48 hours after stroke. The combination treatment significantly improved neurological deficits compared with mice treated with tPA or vehicle alone. These neuroprotective effects were associated with significant reductions in fibrin deposits in ischemic vessels and less severe cell death in ischemic brain. The effect of rADAMTS13 on tPA neurotoxicity was mimicked by the N-methyl-D-aspartate (NMDA) receptor antagonist M-801, and was abolished by injection of NMDA. Moreover, rADAMTS 13 prevents the neurotoxicity effect of tPA, by blocking its interaction with the NMDA receptor NR2B and the attendant phosphorylation of NR2B and activation of ERK1/2. Finally, the NR2B-specific NMDA receptor antagonist ifenprodil abolished tPA neurotoxicity and rADAMTS 13 treatment had no further beneficial effect. Our data suggest that the combination of rADAMTS 13 and tPA may provide a novel treatment of ischemic stroke by diminishing the neurotoxic effects of exogenous tPA. PMID- 27181027 TI - Tumor-suppressive activity of 1,25-dihydroxyvitamin D3 against kidney cancer cells via up-regulation of FOXO3. AB - 1,25-Dihydroxyvitamin D3 has been known to have the tumor-suppressive activity in various kinds of tumors. However, the exact effect and working mechanism of 1,25 dihydroxyvitamin D3 on the tumor-suppressive activity in human kidney cancer cells remains poorly understood. 1,25-Dihydroxyvitamin D3 has cytotoxicity to ACHN cells and inhibited ACHN cell proliferation compared to the vehicle control. 1,25-Dihydroxyvitamin D3 increased the expression of the cleaved PARP1, active Caspase3, Bax, and Bim but decreased the expression of Bcl2 in ACHN cells. Moreover, 1,25-dihydroxyvitamin D3 down-regulated the phosphorylated Akt and Erk which might lead to apoptosis through activation of FOXO3 in ACHN cells. Transfection of siRNA against FOXO3 attenuated the pro-apoptotic BimEL expression in ACHN cells treated with 1,25-dihydroxyvitamin D3. These results suggest that FOXO3 is involved in the apoptosis induced by 1,25-dihydroxyvitamin D3. PMID- 27181028 TI - Two-dimensional stanane: strain-tunable electronic structure, high carrier mobility, and pronounced light absorption. AB - By means of state-of-the-art density functional theory (DFT) computations, we systematically studied the structural, electronic, and optical properties of a novel two dimensional material, namely stanane (SnH). According to our computational results, stanane is semiconducting with a direct band gap of 1.00 eV, which can be flexibly tuned by applying an external strain. Remarkably, stanane has much higher electron and hole mobilities than those of a MoS2 monolayer at room temperature. Moreover, stanane has rather strong optical absorption in the visible as well as infrared regions of the solar spectrum. These results provide many useful insights for the wide application of stanane in electronics and optoelectronics. PMID- 27181029 TI - Developmental changes in the hypothalamic mRNA expression levels of PACAP and its receptor PAC1 and their sensitivity to fasting in male and female rats. AB - The actions and responses of hypothalamic appetite regulatory and factors change markedly during the neonatal to pre-pubertal period. Pituitary adenylate cyclase activating polypeptide (PACAP) has been found to play pivotal roles in the regulation of metabolic and nutritional status through its specific receptor PAC1. PACAP/PAC1 have anorectic roles, and their functions are regulated by leptin in adulthood. In the present study, we showed that hypothalamic PACAP mRNA expression decreases during the neonatal to pre-pubertal period (from postnatal day 10-30) in both male and female rats. During this period, hypothalamic PACAP mRNA expression was not affected by 24h fasting in either sex, while the serum leptin levels (leptin is a positive regulator of hypothalamic PACAP expression in adulthood) of both sexes were decreased by fasting. On the other hand, hypothalamic PAC1 mRNA expression did not change during the neonatal to pre pubertal period in either sex; however, its levels were consistently higher in males than in females. Hypothalamic PAC1 mRNA expression was decreased by 24h fasting in males, but no such changes were observed in females. These results indicate while hypothalamic PACAP expression is sensitive to a negative energy state and the serum leptin level in adulthood, no such relationships are seen in the pre-pubertal period. In addition, we speculate that differences in the gonadal steroidal milieu might induce sexual dimorphism in the basal hypothalamic PAC1 mRNA level and its response to fasting. The mechanisms responsible for and the physiological effects of such changes in hypothalamic PACAP and PAC1 expression during the developmental period remain to be clarified. PMID- 27181031 TI - Na domhain shamhlaiochta: formulary submission guidelines in Ireland and the standards of normal science. AB - In common with a number of other single payer health systems, Ireland, through the Health Information and Quality Authority, has established guidelines for formulary submissions by pharmaceutical manufacturers. In the last few months, however, there have been a number of questions raised as to whether or not guidelines for economic evaluations in such submissions are consistent with the standards of normal science. Do they require those making the submission to put their claims in the form of testable hypotheses that can support falsification and replication? The purpose of this commentary is to consider whether the 2014 guidelines meet these standards. The assessment presented argues that the guidelines do not meet the standards of normal science. Instead, from this perspective, they are best characterized as na domhain shamhlaiochta (imaginary or false worlds). There is no requirement in the guidelines for claims to be expressed as testable propositions, as hypotheses for expected impact that can be evaluated and the outcomes reported as part of ongoing disease area and therapeutic class reviews. The commentary concludes with suggestions for a reworking of the guidelines to meet the standards of normal science. PMID- 27181030 TI - The validity of dysthymia to predict clinical depressive symptoms as measured by the Hamilton Depression Scale at the 5-year follow-up of patients with first episode depression. AB - BACKGROUND: In long-term follow-up studies on depression, the Eysenck Neuroticism Scale (ENS) at the score level of dysthymia has been found to be valid at predicting poor outcome. AIMS: The ENS dysthymia level was compared with the Beck Depression Inventory (BDI) level to predict the prevalence of depressive symptoms at the 5-year follow-up of patients initially diagnosed with first episode depression using the Hamilton Depression Scale (HAM-D) to express depressive symptoms. METHODS: A total of 301 in- or outpatients aged 18-70 years with a recent single depressive episode were assessed by ENS, BDI, and HAM-D from 2005 2007. At 5-year follow-up from 2011-2013, the participants were re-assessed by HAM-D. The HAM-D was used to measure depressive symptoms at the 5-year follow-up. The Mokken analysis was used to indicate scalability of the BDI and ENS. RESULTS: A total of 185 participants were available for the psychometric analysis of the ESN and BDI, and the scalability was found acceptable. In total, 99 patients were available for the predictive analysis. Both the ENS and the BDI were significantly associated with depressive symptoms (HAM-D17 >= 8) at the 5-year follow-up (p < 0.05). CONCLUSION: Dysthymia as measured by the two self-rating scales ENS and BDI can be considered part of a 'double depression' in patients with first episode depression, implying an existence of depressive symptoms at the 5-year follow-up. CLINICAL IMPLICATIONS: Evaluation of dysthymia or neuroticism is important to perform, even in patients with first episode depression, in order to identify 'double depression'. PMID- 27181032 TI - Multiplexed labeling system for high-throughput cell sorting. AB - Flow cytometry and fluorescence activated cell sorting techniques were designed to realize configurable classification and separation of target cells. A number of cell phenotypes with different functionalities have recently been revealed. Before simultaneous selective capture of cells, it is desirable to label different samples with the corresponding dyes in a multiplexing manner to allow for a single analysis. However, few methods to obtain multiple fluorescent colors for various cell types have been developed. Even when restricted laser sources are employed, a small number of color codes can be expressed simultaneously. In this study, we demonstrate the ability to manifest DNA nanostructure-based multifluorescent colors formed by a complex of dyes. Highly precise self-assembly of fluorescent dye-conjugated oligonucleotides gives anisotropic DNA nanostructures, Y- and tree-shaped DNA (Y-DNA and T-DNA, respectively), which may be used as platforms for fluorescent codes. As a proof of concept, we have demonstrated seven different fluorescent codes with only two different fluorescent dyes using T-DNA. This method provides maximum efficiency for current flow cytometry. We are confident that this system will provide highly efficient multiplexed fluorescent detection for bioanalysis compared with one-to-one fluorescent correspondence for specific marker detection. PMID- 27181034 TI - Putting the cart before the horse: A cost effectiveness analysis of treatments for stuttering in young children requires evidence that the treatments analyzed were effective. AB - PURPOSE: To investigate the validity of findings from a recent study reported in this journal by de Sonneville-Koedoot, Bouwmans, Franken, and Stolk (2015) on the cost effectiveness of two programs for treating young children who stutter. METHODS: The de Sonneville-Koedoot, Bouwmans et al. study was based directly on the results obtained in an earlier study, known as the RESTART-study, which compared the outcomes from the Lidcombe Program and a Demands and Capacities Model program. The methodology of the RESTART-study was critically reviewed. RESULTS: The absence of an untreated control group in the RESTART-study makes the results of that study uninterpretable. An inappropriate comparison made with the Yairi and Ambrose (2005) Illinois Study findings failed to resolve the control group problem. Furthermore, the criteria used to classify treated children as "non-stuttering" was also shown to be confounded. The foregoing problems meant that neither treatment program could be shown to be more effective than no treatment. CONCLUSION: de Sonneville-Koedoot, Bouwmans et al's findings, which compared the cost effectiveness of two treatments for young children who stutter, have no value for clinical management because the treatments investigated were not shown to be more effective than no treatment. PMID- 27181036 TI - Failing Left Ventricles Have an Enhanced Post-Stimulation Potentiation Despite Their Impaired Force Frequency Relationship. AB - The left ventricular contractile force (LV dP/dtmax) of patients with left ventricular systolic dysfunction does not increase effectively with an increase in heart rate. In other words, their force-frequency relationship (FFR) is impaired. However, it is unknown whether a longer coupling interval subsequent to tachycardia causes a stronger contraction (poststimulation potentiation, PSP) in a rate-dependent manner.In 16 patients with idiopathic dilated cardiomyopathy (DCM) (48 +/- 2 years old, LVEF 30 +/- 10%) and 6 control patients (58 +/- 4 years old, LVEF 70 +/- 7%), FFR was assessed by right atrial pacing using a micro manometer-tipped catheter. At each pacing rate, the increase of LV dP/dtmax over basal LV dP/dt (DeltaFFR) and the increase of LV dP/dtmax of the first beat after pacing cessation over LV dP/dtmax during pacing (DeltaPSP) were evaluated.Patients with DCM had smaller LV dP/dtmax at baseline (872 +/- 251 versus 1370 +/- 123 mmHg/second, P = 0.0002) and developed smaller DeltaFFR (eg, at 120/minute, 77 +/- 143 versus 331 +/- 131 mmHg/second, P = 0.0011). In contrast, they showed a rate-dependent increase of LV dP/dtmax of PSP and had greater DeltaPSP (eg, at 120/minute, 294 +/- 173 versus -152 +/- 131 mmHg/second, P < 0.0001).Failing left ventricles develop little contractile force during tachycardia despite their rate-dependent enhancement in post-stimulation potentiation, suggesting that refractoriness of contractile force underlies impaired FFR. PMID- 27181035 TI - Coral Sr/Ca-based sea surface temperature and air temperature variability from the inshore and offshore corals in the Seribu Islands, Indonesia. AB - The ability of massive Porites corals to faithfully record temperature is assessed. Porites corals from Kepulauan Seribu were sampled from one inshore and one offshore site and analyzed for their Sr/Ca variation. The results show that Sr/Ca of the offshore coral tracked SST, while Sr/Ca variation of the inshore coral tracked ambient air temperature. In particular, the inshore SST variation is related to air temperature anomalies of the urban center of Jakarta. The latter we relate to air-sea interactions modifying inshore SST associated with the land-sea breeze mechanism and/or monsoonal circulation. The correlation pattern of monthly coral Sr/Ca with the Nino3.4 index and SEIO-SST reveals that corals in the Seribu islands region respond differently to remote forcing. An opposite response is observed for inshore and offshore corals in response to El Nino onset, yet similar to El Nino mature phase (December to February). SEIO SSTs co-vary strongly with SST and air temperature variability across the Seribu island reef complex. The results of this study clearly indicate that locations of coral proxy record in Indonesia need to be chosen carefully in order to identify the seasonal climate response to local and remote climate and anthropogenic forcing. PMID- 27181033 TI - alpha-Amanitin Restrains Cancer Relapse from Drug-Tolerant Cell Subpopulations via TAF15. AB - Cancer relapse occurs with substantial frequency even after treatment with curative intent. Here we studied drug-tolerant colonies (DTCs), which are subpopulations of cancer cells that survive in the presence of drugs. Proteomic characterization of DTCs identified stemness- and epithelial-dominant subpopulations, but functional screening suggested that DTC formation was regulated at the transcriptional level independent from protein expression patterns. We consistently found that alpha-amanitin, an RNA polymerase II (RNAPII) inhibitor, effectively inhibited DTCs by suppressing TAF15 expression, which binds to RNA to modulate transcription and RNA processing. Sequential administration of alpha-amanitin and cisplatin extended overall survival in a cancer-relapse mouse model, namely peritonitis carcinomatosa. Therefore, post treatment cancer relapse may occur through non-distinct subpopulations and may be effectively prevented by alpha-amanitin to disrupt transcriptional machinery, including TAF15. PMID- 27181037 TI - Reduction of Fluoroscopic Exposure Using a New Fluoroscopy Integrating Technology in a 3D-Mapping System During Pulmonary Vein Isolation With a Circular Multipolar Irrigated Catheter. AB - Pulmonary vein isolation (PVI) is a cornerstone therapy in patients with atrial fibrillation (AF). With increasing numbers of PVI procedures, demand arises to reduce the cumulative fluoroscopic radiation exposure for both the physician and the patient. New technologies are emerging to address this issue. Here, we report our first experiences with a new fluoroscopy integrating technology in addition to a current 3D-mapping system. The new fluoroscopy integrating system (FIS) with 3D-mapping was used prospectively in 15 patients with AF. Control PVI cases (n = 37) were collected retrospectively as a complete series. Total procedure time (skin to skin), fluoroscopic time, and dose-area-product (DAP) data were analyzed. All PVI procedures were performed by one experienced physician using a commercially available circular multipolar irrigated ablation catheter. All PVI procedures were successfully undertaken without major complications. Baseline characteristics of the two groups showed no significant differences. In the group using the FIS, the fluoroscopic time and DAP were significantly reduced from 571 +/- 187 seconds versus 1011 +/- 527 seconds (P = 0.0029) and 4342 +/- 2073 cGycm(2) versus 6208 +/- 3314 cGycm(2) (P = 0.049), respectively. Mean procedure time was not significantly affected and was 114 +/- 31 minutes versus 104 +/- 24 minutes (P = 0.23) by the FIS.The use of the new FIS with the current 3D-mapping system enables a significant reduction of the total fluoroscopy time and DAP compared to the previous combination of 3D-mapping system plus normal fluoroscopy during PVI utilizing a circular multipolar irrigated ablation catheter. However, the concomitant total procedure time is not affected. Thus, the new system reduces the radiation exposure for both the physicians and patients. PMID- 27181038 TI - Efficacy and Limitations of Tachycardia Detection Interval Guided Reprogramming for Reduction of Inappropriate Shock in Implantable Cardioverter-Defibrillator Patients. AB - The avoidance of inappropriate shock therapy is an important clinical issue in implantable cardioverter-defibrillator (ICD) patients. We retrospectively analyzed therapeutic events in ICD patients, and the effect of tachycardia detection interval (TDI) and tachycardia cycle length (TCL) guided reprograming on the reduction of inappropriate ICD therapy. The clinical determinants of after reprogramming were also evaluated.A total of 254 consecutive ICD patients were included in the study, and the incidence of antitachycardia therapy was evaluated during the follow-up period of 27.3 +/- 18.7 months. When inappropriate antitachycardia therapy appeared, TDI was reprogrammed not to exceed the detected TCL and the patients continued to be followed-up. Various clinical parameters were compared between patients with and without inappropriate ICD therapy. During the initial follow-up period of 18.6 +/- 15.6 months, ICD therapy occurred in 127/254 patients (50%) including inappropriate antitachycardia pacing (ATP) (12.9%) and shock (44.35%). Determinants of initial inappropriate therapy were dilated cardiomyopathy (DCM), history of therapeutic hypothermia, and QRS duration. Of the 61 patients with inappropriate therapy, 24 received TCL guided reprogramming. During the additional observation period of 17.0 +/- 16.8 months, inappropriate therapy recurred in 5/24 patients (2 ATP, 3 shocks). The determinant of these inappropriate therapy events after reprogramming was the presence of supraventricular tachycardia.By applying simple TCL and TDI guided reprogramming, inappropriate therapy was reduced by 79%. The determinant of inappropriate therapy after reprogramming was the presence of supraventricular tachycardia. PMID- 27181039 TI - Bilateral Subclavian Vein Occlusion in a SAPHO Syndrome Patient Who Needed an Implantable Cardioverter Defibrillator. AB - A 79-year-old Asian man was hospitalized because of progressive exertional dyspnea with decreasing left ventricular ejection fraction and frequent non sustained ventricular tachycardia. Pre-procedure venography for implantable cardioverter defibrillator (ICD) implantation showed occlusion of the bilateral subclavian veins. In consideration of subcutaneous humps in the sterno-clavicular area and palmoplantar pustulosis, we diagnosed him as having synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome and speculated that it induced peri-osteal chronic inflammation in the sterno-clavicular area, resulting in occlusion of the adjacent bilateral subclavian veins. An automatic external defibrillator (AED) was installed in the patient's house and total subcutaneous ICD was considered. Venous thrombosis in SAPHO syndrome is not frequent but has been reported. To the best of our knowledge, this is the first case of bilateral subclavian vein occlusion in a SAPHO syndrome patient who needs ICD implantation. PMID- 27181040 TI - Low-Level Vagus Nerve Stimulation Reverses Cardiac Dysfunction and Subcellular Calcium Handling in Rats With Post-Myocardial Infarction Heart Failure. AB - Vagus nerve stimulation (VNS), targeting the imbalanced autonomic nervous system, is a promising therapeutic approach for chronic heart failure (HF). Moreover, calcium cycling is an important part of cardiac excitation-contraction coupling (ECC), which also participates in the antiarrhythmic effects of VNS. We hypothesized that low-level VNS (LL-VNS) could improve cardiac function by regulation of intracellular calcium handling properties. The experimental HF model was established by ligation of the left anterior descending coronary artery (LAD). Thirty-two male Sprague-Dawley rats were divided into 3 groups as follows; control group (sham operated without coronary ligation, n = 10), HF-VNS group (HF rats with VNS, n = 12), and HF-SS group (HF rats with sham nerve stimulation, n = 10). After 8 weeks of treatment, LL-VNS significantly improved left ventricular ejection fraction (LVEF) and attenuated myocardial interstitial fibrosis in the HF-VNS group compared with the HF-SS group. Elevated plasma norepinephrine and dopamine, but not epinephrine, were partially reduced by LL-VNS. Additionally, LL VNS restored the protein and mRNA levels of sarcoplasmic reticulum Ca(2+) ATPase (SERCA2a), Na(+)-Ca(2+) exchanger 1 (NCX1), and phospholamban (PLB) whereas the expression of ryanodine receptor 2 (RyR2) as well as mRNA level was unaffected. Thus, our study results suggest that the improvement of cardiac performance by LL VNS is accompanied by the reversal of dysfunctional calcium handling properties including SERCA2a, NCX1, and PLB which may be a potential molecular mechanism of VNS for HF. PMID- 27181041 TI - Everolimus-Incorporated Therapy Reduces Myocardial Hypertrophy in Recipients of Heart Transplantation. PMID- 27181043 TI - Cardiac Troponin as a Specific and Non-Specific Biomarker for Cardiovascular Events. PMID- 27181042 TI - Pathophysiology and Management of Cardiovascular Manifestations in Marfan and Loeys-Dietz Syndromes. AB - Marfan syndrome (MFS) is an autosomal dominant heritable disorder of connective tissue that affects the cardiovascular, skeletal, ocular, pulmonary, and nervous systems and is usually caused by mutations in the FBN1 gene, which encodes fibrillin-1. MFS is traditionally considered to result from the structural weakness of connective tissue. However, recent investigations on molecular mechanisms indicate that increased transforming growth factor-beta (TGF-beta) activity plays a crucial role in the pathogenesis of MFS and related disorders, such as Loeys-Dietz syndrome (LDS), which is caused by mutation in TGF-beta signaling-related genes. In addition, recent studies show that angiotensin II type 1 receptor (AT1R) signaling enhances cardiovascular pathologies in MFS, and the angiotensin II receptor blocker losartan has the potential to inhibit aortic aneurysm formation. However, the relationship between TGF-beta and AT1R signaling pathways remains poorly characterized. In this review, we discuss the recent studies on the molecular mechanisms underlying cardiovascular manifestations of MFS and LDS and the ensuing strategies for management. PMID- 27181044 TI - Does Mechanical Stress Regulate the Angiogenic Profile of Endothelial Progenitor Cells? PMID- 27181047 TI - Prevalence of neoplasms in definite and probable mitochondrial disorders. AB - There are some indications that the prevalence of benign and malign neoplasms is increased in patients with a mitochondrial disorder (MID). This study aimed at calculating the prevalence of malign and benign neoplasms in MID patients compared to the general population. Among 103 adult patients with definite or probable MID 16 had a malignancy (15.5%) and 11 (10.7%) a benign neoplasm. Four patients had thyroid cancer, three patients had prostate cancer, two patients each colon cancer, or ovarian cancer, and one each lung cancer, basalioma, Paget carcinoma of the skin, Bowen disease, renal cancer, and urinary bladder cancer. One patient had two carcinomas. Five patients had lipomas, two thyroid adenoma, and one each meningeoma, ovarian adenoma, hemangioma of the liver, and pituitary adenoma. Compared to the general population, the prevalence of malignancies was 3 4 fold increased in definite and probable MIDs. Compared to a cohort of myotonic dystrophy type-1 patients, the prevalence was 1.4 fold increased. In conclusion, adult MID patients seem to carry an increased risk to develop malignancy or a benign neoplasm. Females with a MID seem to be predominantly at risk to develop a neoplasm. PMID- 27181045 TI - Contribution of Candida biomarkers and DNA detection for the diagnosis of invasive candidiasis in ICU patients with severe abdominal conditions. AB - BACKGROUND: To assess the performance of Candida albicans germ tube antibody (CAGTA), (1 -> 3)-beta-D-glucan (BDG), mannan antigen (mannan-Ag), anti-mannan antibodies (mannan-Ab), and Candida DNA for diagnosing invasive candidiasis (IC) in ICU patients with severe abdominal conditions (SAC). METHODS: A prospective study of 233 non-neutropenic patients with SAC on ICU admission and expected stay >= 7 days. CAGTA (cutoff positivity >= 1/160), BDG (>=80, 100 and 200 pg/mL), mannan-Ag (>=60 pg/mL), mannan-Ab (>=10 UA/mL) were measured twice a week, and Candida DNA only in patients treated with systemic antifungals. IC diagnosis required positivities of two biomarkers in a single sample or positivities of any biomarker in two consecutive samples. Patients were classified as neither colonized nor infected (n = 48), Candida spp. colonization (n = 154) (low-grade, n = 130; high-grade, n = 24), and IC (n = 31) (intra-abdominal candidiasis, n = 20; candidemia, n = 11). RESULTS: The combination of CAGTA and BDG positivities in a single sample or at least one of the two biomarkers positive in two consecutive samples showed 90.3 % (95 % CI 74.2-98.0) sensitivity, 42.1 % (95 % CI 35.2-98.8) specificity, and 96.6 % (95 % CI 90.5-98.8) negative predictive value. BDG positivities in two consecutive samples had 76.7 % (95 % CI 57.7-90.1) sensitivity and 57.2 % (95 % CI 49.9-64.3) specificity. Mannan-Ag, mannan-Ab, and Candida DNA individually or combined showed a low discriminating capacity. CONCLUSIONS: Positive Candida albicans germ tube antibody and (1 -> 3)-beta-D glucan in a single blood sample or (1 -> 3)-beta-D-glucan positivity in two consecutive blood samples allowed discriminating invasive candidiasis from Candida spp. colonization in critically ill patients with severe abdominal conditions. These findings may be helpful to tailor empirical antifungal therapy in this patient population. PMID- 27181046 TI - Analysis of Mitochondrial haemoglobin in Parkinson's disease brain. AB - Mitochondrial dysfunction is an early feature of neurodegeneration. We have shown there are mitochondrial haemoglobin changes with age and neurodegeneration. We hypothesised that altered physiological processes are associated with recruitment and localisation of haemoglobin to these organelles. To confirm a dynamic localisation of haemoglobin we exposed Drosophila melanogaster to cyclical hypoxia with recovery. With a single cycle of hypoxia and recovery we found a relative accumulation of haemoglobin in the mitochondria compared with the cytosol. An additional cycle of hypoxia and recovery led to a significant increase of mitochondrial haemoglobin (p<0.05). We quantified ratios of human mitochondrial haemoglobin in 30 Parkinson's and matched control human post-mortem brains. Relative mitochondrial/cytosolic quantities of haemoglobin were obtained for the cortical region, substantia nigra and cerebellum. In age matched post mortem brain mitochondrial haemoglobin ratios change, decreasing with disease duration in female cerebellum samples (n=7). The change is less discernible in male cerebellum (n=18). In cerebellar mitochondria, haemoglobin localisation in males with long disease duration shifts from the intermembrane space to the outer membrane of the organelle. These new data illustrate dynamic localisation of mitochondrial haemoglobin within the cell. Mitochondrial haemoglobin should be considered in the context of gender differences characterised in Parkinson's disease. It has been postulated that cerebellar circuitry may be activated to play a protective role in individuals with Parkinson's. The changing localisation of intracellular haemoglobin in response to hypoxia presents a novel pathway to delineate the role of the cerebellum in Parkinson's disease. PMID- 27181048 TI - Accurate quantification of mouse mitochondrial DNA without co-amplification of nuclear mitochondrial insertion sequences. AB - BACKGROUND: Mitochondria contain an extra-nuclear genome in the form of mitochondrial DNA (MtDNA), damage to which can lead to inflammation and bioenergetic deficit. Changes in MtDNA levels are increasingly used as a biomarker of mitochondrial dysfunction. We previously reported that in humans, fragments in the nuclear genome known as nuclear mitochondrial insertion sequences (NumtS) affect accurate quantification of MtDNA. In the current paper our aim was to determine whether mouse NumtS affect the quantification of MtDNA and to establish a method designed to avoid this. METHODS: The existence of NumtS in the mouse genome was confirmed using blast N, unique MtDNA regions were identified using FASTA, and MtDNA primers which do not co-amplify NumtS were designed and tested. MtDNA copy numbers were determined in a range of mouse tissues as the ratio of the mitochondrial and nuclear genome using real time qPCR and absolute quantification. RESULTS: Approximately 95% of mouse MtDNA was duplicated in the nuclear genome as NumtS which were located in 15 out of 21 chromosomes. A unique region was identified and primers flanking this region were used. MtDNA levels differed significantly in mouse tissues being the highest in the heart, with levels in descending order (highest to lowest) in kidney, liver, blood, brain, islets and lung. CONCLUSION: The presence of NumtS in the nuclear genome of mouse could lead to erroneous data when studying MtDNA content or mutation. The unique primers described here will allow accurate quantification of MtDNA content in mouse models without co-amplification of NumtS. PMID- 27181050 TI - Role and modulation of drug transporters in HIV-1 therapy. AB - Current treatment of human immunodeficiency virus type-1 (HIV-1) infection involves a combination of antiretroviral drugs (ARVs) that target different stages of the HIV-1 life cycle. This strategy is commonly referred to as highly active antiretroviral therapy (HAART) or combined antiretroviral therapy (cART). Membrane-associated drug transporters expressed ubiquitously in mammalian systems play a crucial role in modulating ARV disposition during HIV-1 infection. Members of the ATP-binding cassette (ABC) and solute carrier (SLC) transporter superfamilies have been shown to interact with ARVs, including those that are used as part of first-line treatment regimens. As a result, the functional expression of drug transporters can influence the distribution of ARVs at specific sites of infection. In addition, pathological factors related to HIV-1 infection and/or ARV therapy itself can alter transporter expression and activity, thus further contributing to changes in ARV disposition and the effectiveness of HAART. This review summarizes current knowledge on the role of drug transporters in regulating ARV transport in the context of HIV-1 infection. PMID- 27181049 TI - CD23 can negatively regulate B-cell receptor signaling. AB - CD23 has been implicated as a negative regulator of IgE and IgG antibody responses. However, whether CD23 has any role in B-cell activation remains unclear. We examined the expression of CD23 in different subsets of peripheral B cells and the impact of CD23 expression on the early events of B-cell receptor (BCR) activation using CD23 knockout (KO) mice. We found that in addition to marginal zone B cells, mature follicular B cells significantly down regulate the surface expression level of CD23 after undergoing isotype switch and memory B cell differentiation. Upon stimulation with membrane-associated antigen, CD23 KO causes significant increases in the area of B cells contacting the antigen presenting membrane and the magnitude of BCR clustering. This enhanced cell spreading and BCR clustering is concurrent with increases in the levels of phosphorylation of tyrosine and Btk, as well as the levels of F-actin and phosphorylated Wiskott Aldrich syndrome protein, an actin nucleation promoting factor, in the contract zone of CD23 KO B cells. These results reveal a role of CD23 in the negative regulation of BCR signaling in the absence of IgE immune complex and suggest that CD23 down-regulates BCR signaling by influencing actin mediated BCR clustering and B-cell morphological changes. PMID- 27181051 TI - Ces3/TGH Deficiency Attenuates Steatohepatitis. AB - Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in developed countries. NAFLD describes a wide range of liver pathologies from simple steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. NASH is distinguished from simple steatosis by inflammation, cell death and fibrosis. In this study we found that mice lacking triacylglycerol hydrolase (TGH, also known as carboxylesterase 3 or carboxylesterase 1d) are protected from high-fat diet (HFD) - induced hepatic steatosis via decreased lipogenesis, increased fatty acid oxidation and improved hepatic insulin sensitivity. To examine the effect of the loss of TGH function on the more severe NAFLD form NASH, we ablated Tgh expression in two independent NASH mouse models, Pemt(-/-) mice fed HFD and Ldlr( /-) mice fed high-fat, high-cholesterol Western-type diet (WTD). TGH deficiency reduced liver inflammation, oxidative stress and fibrosis in Pemt(-/-) mice. TGH deficiency also decreased NASH in Ldlr(-/-) mice. Collectively, these findings indicate that TGH deficiency attenuated both simple hepatic steatosis and irreversible NASH. PMID- 27181052 TI - Are there any differences in mandibular morphology of patients with bisphosphonate-related osteonecrosis of jaws?: a case-control study. AB - OBJECTIVES: The aim of this study was to compare the morphological differences in the mandible between patients with bisphosphonate-related osteonecrosis of the jaw (BRONJ) and healthy individuals and to detect the correlation between these parameters on panoramic radiography and CBCT. METHODS: The CBCT and panoramic images of patients with BRONJ (n = 32) and control groups (n = 32) were included in the study. All the comparisons were analyzed between the osteonecrosed and healthy sides of patients with BRONJ and control group. The panoramic radiographs were used to measure the values of the condyle angle, gonial angle, antegonial angle, antegonial depth, condylar height and ramal height. The mandibular cortical index (MCI) and bone quality index (BQI) were also examined on cross sectional scans of CBCT images. RESULTS: There were significant differences in the MCI (p = 0.014) and BQI (p = 0.021) between the left and right side of the BRONJ group and also between the osteonecrosed side of the BRONJ and control group (p < 0.0001). No significant difference was found in other comparisons. CONCLUSIONS: The outcomes of the present study indicate that bisphosphonates influenced some internal morphological changes in the mandible. These changes may be a reason of BRONJ. But, these changes are not reflective of the measured values obtained using panoramic radiographs on the external morphology of the mandible. PMID- 27181054 TI - A sobering reminder that heavy drinking and heart failure do not mix. PMID- 27181053 TI - Infectiousness of HIV-Seropositive Patients with Tuberculosis in a High-Burden African Setting. AB - RATIONALE: Policy recommendations on contact investigation of HIV-seropositive patients with tuberculosis have changed several times. Current epidemiologic evidence informing these recommendations is considered low quality, and few large studies investigating the infectiousness of HIV-seropositive and -seronegative index cases have been performed in sub-Saharan Africa. OBJECTIVES: We assessed the infectiousness of HIV-seropositive and -seronegative patients with tuberculosis to their household contacts and examined potential modifiers of this relationship. METHODS: Adults suffering from their first episode of pulmonary tuberculosis were identified in Kampala, Uganda. Field workers visited index households and enrolled consenting household contacts. Latent tuberculosis infection was measured through tuberculin skin testing, and relative risks were calculated using modified Poisson regression models. Standard assessments of interaction between latent tuberculosis infection, the HIV serostatus of index cases, and other variables were performed. MEASUREMENTS AND MAIN RESULTS: Latent tuberculosis infection was found in 577 of 878 (65.7%) and 717 of 974 (73.6%) household contacts of HIV-seropositive and -seronegative tuberculosis cases (relative risk, 0.89; 95% confidence interval, 0.82-0.97). On further stratification, cavitary lung disease (P < 0.0001 for interaction) and smear status (P = 0.02 for interaction) of tuberculosis cases modified the infectiousness of HIV-seropositive indexes. Cough duration of index cases did not display interaction (P = 0.499 for interaction). CONCLUSIONS: This study suggests that HIV-seropositive tuberculosis cases may be less infectious than HIV seronegative patients only when they are smear-negative or lack cavitary lung disease. These results may explain heterogeneity between prior studies and provide evidence suggesting that tuberculosis contact investigation should include HIV-seropositive index cases in high disease burden settings. PMID- 27181055 TI - Saliva ferning, an unorthodox estrus detection method in water buffaloes (Bubalus bubalis). AB - Estrus detection is a major problem in buffalo husbandry because of inconsistent expression of estrous signs at different seasons, and a high prevalence of the silent heat and postpartum anestrus in this species. Around 50% of the estrus events in buffaloes are currently undetected in the field conditions, resulting in a huge economic loss. Although the cervicovaginal fluid fern patterns confirm the estrus for a breeding decision, the fluid discharge is absent during the silent-heat condition. Therefore, the present study focused on the crystallization patterns of the saliva as an alternative method for estrus detection in buffaloes. Saliva is a body fluid available regularly, and its ferning ability before ovulation was established in women. In this study, eight female nonpregnant Murrah buffaloes (Bubalus bubalis) were considered during two experimental periods of 3 months each. One period was in summer with five animals, and another period was in rainy season with three animals. Estrus was determined by the estrus symptoms, ovarian ultrasonography, and salivary estradiol (E2) to progesterone (P4) ratio. A total of 450 saliva samples were collected from these animals on the daily basis. The salivary smear was prepared with 20 MUL of the cell-free saliva on a clean glass slide, and its microscopic images were captured at a magnification of * 200. The images were used for fractal analysis as the salivary crystallization or fern patterns follow the fractal geometry. Saliva at estrus showed a typical symmetrical fern-like crystallization patterns with significantly (P < 0.05) lower fractal dimension values. Salivary estradiol levels and E2/P4 ratio were significantly (P < 0.05) higher at the estrus stage than those at the diestrus stage. An average period of an estrous cycle was 21.7 +/- 2.7 days (n = 18 estrous cycles) in buffaloes on the basis of distinct salivary crystallization patterns. The proportion of estrus detection by the salivary fern patterns was very significantly (P < 0.01) higher (0.84) than the proportion of estrus detection (0.5) in the field conditions. Altogether, salivary fern patterns along with the current methods can help reduce estrus detection problem in buffaloes. PMID- 27181056 TI - Quantum versus simulated annealing in wireless interference network optimization. AB - Quantum annealing (QA) serves as a specialized optimizer that is able to solve many NP-hard problems and that is believed to have a theoretical advantage over simulated annealing (SA) via quantum tunneling. With the introduction of the D Wave programmable quantum annealer, a considerable amount of effort has been devoted to detect and quantify quantum speedup. While the debate over speedup remains inconclusive as of now, instead of attempting to show general quantum advantage, here, we focus on a novel real-world application of D-Wave in wireless networking-more specifically, the scheduling of the activation of the air-links for maximum throughput subject to interference avoidance near network nodes. In addition, D-Wave implementation is made error insensitive by a novel Hamiltonian extra penalty weight adjustment that enlarges the gap and substantially reduces the occurrence of interference violations resulting from inevitable spin bias and coupling errors. The major result of this paper is that quantum annealing benefits more than simulated annealing from this gap expansion process, both in terms of ST99 speedup and network queue occupancy. It is the hope that this could become a real-word application niche where potential benefits of quantum annealing could be objectively assessed. PMID- 27181058 TI - Error Signals in Motor Cortices Drive Adaptation in Reaching. AB - Reaching movements are subject to adaptation in response to errors induced by prisms or external perturbations. Motor cortical circuits have been hypothesized to provide execution errors that drive adaptation, but human imaging studies to date have reported that execution errors are encoded in parietal association areas. Thus, little evidence has been uncovered that supports the motor hypothesis. Here, we show that both primary motor and premotor cortices encode information on end-point errors in reaching. We further show that post-movement microstimulation to these regions caused trial-by-trial increases in errors, which subsided exponentially when the stimulation was terminated. The results indicate for the first time that motor cortical circuits provide error signals that drive trial-by-trial adaptation in reaching movements. PMID- 27181057 TI - Improving classification of mature microRNA by solving class imbalance problem. AB - MicroRNAs (miRNAs) are ~20-25 nucleotides non-coding RNAs, which regulated gene expression in the post-transcriptional level. The accurate rate of identifying the start sit of mature miRNA from a given pre-miRNA remains lower. It is noting that the mature miRNA prediction is a class-imbalanced problem which also leads to the unsatisfactory performance of these methods. We improved the prediction accuracy of classifier using balanced datasets and presented MatFind which is used for identifying 5' mature miRNAs candidates from their pre-miRNA based on ensemble SVM classifiers with idea of adaboost. Firstly, the balanced-dataset was extract based on K-nearest neighbor algorithm. Secondly, the multiple SVM classifiers were trained in orderly using the balance datasets base on represented features. At last, all SVM classifiers were combined together to form the ensemble classifier. Our results on independent testing dataset show that the proposed method is more efficient than one without treating class imbalance problem. Moreover, MatFind achieves much higher classification accuracy than other three approaches. The ensemble SVM classifiers and balanced-datasets can solve the class-imbalanced problem, as well as improve performance of classifier for mature miRNA identification. MatFind is an accurate and fast method for 5' mature miRNA identification. PMID- 27181060 TI - Adaptive Prediction Error Coding in the Human Midbrain and Striatum Facilitates Behavioral Adaptation and Learning Efficiency. AB - Effective error-driven learning benefits from scaling of prediction errors to reward variability. Such behavioral adaptation may be facilitated by neurons coding prediction errors relative to the standard deviation (SD) of reward distributions. To investigate this hypothesis, we required participants to predict the magnitude of upcoming reward drawn from distributions with different SDs. After each prediction, participants received a reward, yielding trial-by trial prediction errors. In line with the notion of adaptive coding, BOLD response slopes in the Substantia Nigra/Ventral Tegmental Area (SN/VTA) and ventral striatum were steeper for prediction errors occurring in distributions with smaller SDs. SN/VTA adaptation was not instantaneous but developed across trials. Adaptive prediction error coding was paralleled by behavioral adaptation, as reflected by SD-dependent changes in learning rate. Crucially, increased SN/VTA and ventral striatal adaptation was related to improved task performance. These results suggest that adaptive coding facilitates behavioral adaptation and supports efficient learning. PMID- 27181059 TI - Circuit-wide Transcriptional Profiling Reveals Brain Region-Specific Gene Networks Regulating Depression Susceptibility. AB - Depression is a complex, heterogeneous disorder and a leading contributor to the global burden of disease. Most previous research has focused on individual brain regions and genes contributing to depression. However, emerging evidence in humans and animal models suggests that dysregulated circuit function and gene expression across multiple brain regions drive depressive phenotypes. Here, we performed RNA sequencing on four brain regions from control animals and those susceptible or resilient to chronic social defeat stress at multiple time points. We employed an integrative network biology approach to identify transcriptional networks and key driver genes that regulate susceptibility to depressive-like symptoms. Further, we validated in vivo several key drivers and their associated transcriptional networks that regulate depression susceptibility and confirmed their functional significance at the levels of gene transcription, synaptic regulation, and behavior. Our study reveals novel transcriptional networks that control stress susceptibility and offers fundamentally new leads for antidepressant drug discovery. PMID- 27181064 TI - A new cost-effective and fast method of autologous fat grafting. AB - Due to the increasing number of fat grafting procedures, several laboratories have developed their own fat processing system (Puregraft((r)), LipiVage((r)), Viafill((r)), etc.), such as closed harvesting systems, centrifugation or washing and filtration devices, or even simple decantation techniques. However, all these tissue-engineering systems are expensive. Our team has developed a simple and fast autologous fat grafting system, useable even for a large volume of lipofilling, and based on low-pressure suction and a sterile closed-system for processing the harvested fat tissue. It is a cost-effective system, as it only costs 9.28Eur (10.52USD) for a 500milliliters autologous fat graft procedure. PMID- 27181061 TI - Dopamine Regulation of Lateral Inhibition between Striatal Neurons Gates the Stimulant Actions of Cocaine. AB - Striatal medium spiny neurons (MSNs) form inhibitory synapses on neighboring striatal neurons through axon collaterals. The functional relevance of this lateral inhibition and its regulation by dopamine remains elusive. We show that synchronized stimulation of collateral transmission from multiple indirect pathway MSNs (iMSNs) potently inhibits action potentials in direct-pathway MSNs (dMSNs) in the nucleus accumbens. Dopamine D2 receptors (D2Rs) suppress lateral inhibition from iMSNs to disinhibit dMSNs, which are known to facilitate locomotion. Surprisingly, D2R inhibition of synaptic transmission was larger at axon collaterals from iMSNs than their projections to the ventral pallidum. Targeted deletion of D2Rs from iMSNs impaired cocaine's ability to suppress lateral inhibition and increase locomotion. These impairments were rescued by chemogenetic activation of Gi-signaling in iMSNs. These findings shed light on the functional significance of lateral inhibition between MSNs and offer a novel synaptic mechanism by which dopamine gates locomotion and cocaine exerts its canonical stimulant response. VIDEO ABSTRACT. PMID- 27181062 TI - Melanopsin-Encoded Response Properties of Intrinsically Photosensitive Retinal Ganglion Cells. AB - Melanopsin photopigment expressed in intrinsically photosensitive retinal ganglion cells (ipRGCs) plays a crucial role in the adaptation of mammals to their ambient light environment through both image-forming and non-image-forming visual responses. The ipRGCs are structurally and functionally distinct from classical rod/cone photoreceptors and have unique properties, including single photon response, long response latency, photon integration over time, and slow deactivation. We discovered that amino acid sequence features of melanopsin protein contribute to the functional properties of the ipRGCs. Phosphorylation of a cluster of Ser/Thr residues in the C-terminal cytoplasmic region of melanopsin contributes to deactivation, which in turn determines response latency and threshold sensitivity of the ipRGCs. The poorly conserved region distal to the phosphorylation cluster inhibits phosphorylation's functional role, thereby constituting a unique delayed deactivation mechanism. Concerted action of both regions sustains responses to dim light, allows for the integration of light over time, and results in precise signal duration. PMID- 27181065 TI - Pseudomonas aeruginosa elastase cleaves a C-terminal peptide from human thrombin that inhibits host inflammatory responses. AB - Pseudomonas aeruginosa is an opportunistic pathogen known for its immune evasive abilities amongst others by degradation of a large variety of host proteins. Here we show that digestion of thrombin by P. aeruginosa elastase leads to the release of the C-terminal thrombin-derived peptide FYT21, which inhibits pro-inflammatory responses to several pathogen-associated molecular patterns in vitro and in vivo by preventing toll-like receptor dimerization and subsequent activation of down stream signalling pathways. Thus, P. aeruginosa 'hijacks' an endogenous anti inflammatory peptide-based mechanism, thereby enabling modulation and circumvention of host responses. PMID- 27181066 TI - Rapamycin reduces motivated responding for cocaine and alters GluA1 expression in the ventral but not dorsal striatum. AB - The mechanistic target of rapamycin complex 1 (mTORC1) regulates synaptic protein synthesis and therefore synaptic function and plasticity. A role for mTORC1 has recently been demonstrated for addiction-related behaviors. For example, central or intra-accumbal injections of the mTORC1 inhibitor rapamycin attenuates several indices of cocaine-seeking including progressive ratio (PR) responding and reinstatement. These behavioral effects are associated with decreased mTORC1 activity and synaptic protein translation in the nucleus accumbens (NAC) and point to a possible therapeutic role for rapamycin in the treatment of addiction. Currently, it is unclear whether similar behavioral and biochemical effects can be achieved by administering rapamycin systemically, which represents a more clinically-appropriate route of administration. Here, we assessed the effects of repeated, systemic administration of rapamycin (10mg/kg, i.p.) on PR responding for cocaine. We also assessed whether systemic rapamycin was associated with changes in measures of mTORC1 activity and GluA1 expression in the ventral and dorsal striatum. We report that systemic rapamycin treatment reduced PR breakpoints to levels comparable to intra-NAC rapamycin. Systemic rapamycin treatment also reduced phosphorylated p70S6K and GluA1 AMPARs within the NAC but not dorsal striatum. Thus, systemic administration of rapamycin is as effective at reducing drug seeking behavior and measures of mTORC1 activity compared to direct accumbal application and may therefore represent a possible therapeutic option in the treatment of addiction. Possible caveats of this treatment approach are discussed. PMID- 27181063 TI - Comprehensive genomic analysis reveals FLT3 activation and a therapeutic strategy for a patient with relapsed adult B-lymphoblastic leukemia. AB - The genomic events responsible for the pathogenesis of relapsed adult B lymphoblastic leukemia (B-ALL) are not yet clear. We performed integrative analysis of whole-genome, whole-exome, custom capture, whole-transcriptome (RNA seq), and locus-specific genomic assays across nine time points from a patient with primary de novo B-ALL. Comprehensive genome and transcriptome characterization revealed a dramatic tumor evolution during progression, yielding a tumor with complex clonal architecture at second relapse. We observed and validated point mutations in EP300 and NF1, a highly expressed EP300-ZNF384 gene fusion, a microdeletion in IKZF1, a focal deletion affecting SETD2, and large deletions affecting RB1, PAX5, NF1, and ETV6. Although the genome analysis revealed events of potential biological relevance, no clinically actionable treatment options were evident at the time of the second relapse. However, transcriptome analysis identified aberrant overexpression of the targetable protein kinase encoded by the FLT3 gene. Although the patient had refractory disease after salvage therapy for the second relapse, treatment with the FLT3 inhibitor sunitinib rapidly induced a near complete molecular response, permitting the patient to proceed to a matched-unrelated donor stem cell transplantation. The patient remains in complete remission more than 4 years later. Analysis of this patient's relapse genome revealed an unexpected, actionable therapeutic target that led to a specific therapy associated with a rapid clinical response. For some patients with relapsed or refractory cancers, this approach may indicate a novel therapeutic intervention that could alter outcome. PMID- 27181067 TI - Loading of Gemcitabine on chitosan magnetic nanoparticles increases the anti cancer efficacy of the drug. AB - Targeted delivery of anti-cancer drugs increase the efficacy, while decreasing adverse effects. Among various delivery systems, chitosan coated iron oxide nanoparticles (CsMNPs) gained attention with their biocompatibility, biodegradability, low toxicity and targetability under magnetic field. This study aimed to increase the cellular uptake and efficacy of Gemcitabine. CsMNPs were synthesized by in situ co-precipitation and Gemcitabine was loaded onto the nanoparticles. Nanoparticle characterization was performed by TEM, FTIR, XPS, and zeta potential. Gemcitabine release and stability was analyzed. The cellular uptake was shown. Cytotoxicity of free-Gemcitabine and Gem-CsMNPs were examined on SKBR and MCF-7 breast cancer cells by XTT assay. Gemcitabine loading was optimized as 30uM by spectrophotometric analyses. Drug release was highest (65%) at pH 4.2, while it was 8% at pH 7.2. This is a desired release characteristic since pH of tumor-tissue and endosomes are acidic, while the blood-stream and healthy-tissues are neutral. Peaks reflecting the presence of Gemcitabine were observed in FTIR and XPS. At neutral pH, zeta potential increased after Gemcitabine loading. TEM images displayed, Gem-CsMNPs were 4nm with uniform size distribution and have spherical shape. The cellular uptake and targetability of CsMNPs was studied on MCF-7 breast cancer cell lines. IC50 value of Gem-CsMNPs was 1.4 fold and 2.6 fold lower than free-Gem on SKBR-3 and MCF-7 cell lines respectively, indicating the increased efficacy of Gemcitabine when loaded onto nanoparticles. Targetability by magnetic field, stability, size distribution, cellular uptake and toxicity characteristics of CsMNPs in this study provides a useful targeted delivery system for Gemcitabine in cancer therapy. PMID- 27181068 TI - Protective effects of Celastrol on diethylnitrosamine-induced hepatocellular carcinoma in rats and its mechanisms. AB - Celastrol, an active ingredient of Tripterygium Wilfordii, is a traditional Chinese medicinal herb, which has attracted interests for its potential anti inflammatory and anti-cancer activities. The aim of this study was to evaluate the anti-tumor effect of Celastrol against diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in rats and furthermore, to explore the underlying mechanism. Sprague-Dawley rats were intragastrically administered with DEN (10mg/kg) for 6 days every week and persisting 16 weeks. The number of nodules was calculated. Hematoxylin-Eosin (HE) staining was used to evaluate the hepatic pathological lesions. The levels of serum alanine aminotransferase (ALT), glutamic oxalacetic transaminase (AST), alkaline phosphatase (ALP) and alpha fetoprotein (AFP) were analyzed by Elisa kits, and the protein levels of p53, Murine double minute (MDM) 2, Bax, Bcl-2, Bcl-xl, cytochrome C, Caspase-3, Caspase-9 and Poly (ADP-ribose) polymerase (PARP) were analyzed by western blot. The results showed that Celastrol could significantly decrease the mortality, the number of tumor nodules and the index of liver in the Celastrol groups compared with DEN-treated group. Moreover, Celastrol obviously improved the hepatic pathological lesions and decreased the elevated levels of ALT, AST, ALP and AFP. Meanwhile, Celastrol suppressed the expression of the protein MDM2, activated the intrinsic mitochondrial apoptosis pathway induced by p53, inhibited anti apoptotic Bcl-2 and Bcl-xl, induced the pro-apoptotic Bax, cytochrome C, PARP and caspases. These results suggested that Celastrol had a good therapeutic action in reversing DEN-induced HCC rats, which may be associated with the apoptosis of hepatoma cells induced by Celastrol. PMID- 27181069 TI - In vitro and in vivo corneal effects of latanoprost combined with brimonidine, timolol, dorzolamide, or brinzolamide. AB - To examine the relevance of concentration of benzalkonium chloride (BAK) on the cornea, we investigated the effects of latanoprost containing BAK alone and in combination with other antiglaucoma drug classes on corneal epithelium in vitro in a cultured rabbit corneal cell line (SIRC) and in vivo, using a corneal resistance device (CRD). [In vitro] staten's seruminstitut rabbit corneal cells were exposed to 0.005% latanoprost for 30s, followed by either phosphate buffered saline (control), 0.1% brimonidine, 0.5% timolol, 1% dorzolamide, or 1% brinzolamide. The number of viable cells was counted at 8, 15, and 30min. [In vivo] Albino rabbits were administered one drop of 0.005% latanoprost, followed 5min later by one drop of an agent from the in vitro trial. This was repeated every 15min for a total of three times. The change in corneal barrier function was assessed by measuring the corneal resistance at 2 and 30min after the final administration. [In vitro] At 8min, the viable cell count in the latanoprost+dorzolamide group was significantly lower than in the control group. At 15 and 30min, all treatment groups, except the latanoprost+brimonidine group, demonstrated significantly lower viable cell counts than the control group. [In vivo] At 2min after the final eye drop, the latanoprost+timolol group and the latanoprost+brinzolamide group demonstrated significantly lower corneal resistance than did the latanoprost+brimonidine group. No significant difference was observed between the agents at 30min. In conclusion, when combining latanoprost containing benzalkonium chloride with other classes of antiglaucoma drugs, brimonidine may cause the least corneal damage, and the number of drug administrations may be an important factor. PMID- 27181071 TI - [Unusual localisation of acquired digital fibrokeratoma]. PMID- 27181070 TI - Insulin degludec/insulin aspart in Japanese patients with type 1 diabetes mellitus: Distinct prandial and basal glucose-lowering effects. AB - AIMS/INTRODUCTION: Insulin degludec/insulin aspart (IDegAsp) is a soluble co formulation of long-acting insulin degludec (IDeg) and rapid-acting insulin aspart (IAsp). The present study investigated the pharmacodynamic properties of IDegAsp in Japanese patients with type 1 diabetes mellitus. MATERIALS AND METHODS: In this randomized, double-blind, two-period, cross-over trial, 21 Japanese patients with type 1 diabetes mellitus received single doses of 0.5 U/kg IDegAsp and biphasic insulin aspart 30 in a randomized sequence (13-21 days washout between treatments). The pharmacodynamic response was evaluated in a 26-h euglycemic glucose clamp (target 5.5 mmol/L). Single-dose IDegAsp glucose infusion rate (GIR) profiles were extrapolated to steady state using modeling. RESULTS: The IDegAsp single-dose GIR profile showed a clear distinction between the effects of the bolus (IAsp) and basal (IDeg) components in IDegAsp. When simulated to steady state, the GIR profile of IDegAsp was shifted upwards compared with the single-dose profile, and showed a rapid onset of action and a distinct peak from the IAsp component followed by a separate and sustained basal action from the long-acting IDeg component. For biphasic insulin aspart 30, the initial shape of the GIR profile was similar to IDegAsp, but GIR continuously decreased from maximum and reached zero 18-20 h post-dosing. The characteristics of the GIR profile for IDegAsp were retained when simulated to steady state in a twice-daily dosing regimen. DISCUSSION: In Japanese patients with type 1 diabetes mellitus, the pharmacodynamic profile of IDegAsp is characterized by distinct prandial and basal effects from the IAsp and IDeg components, consistent with what has been reported previously in Caucasian patients with type 1 diabetes mellitus. PMID- 27181072 TI - [Papules on the feet]. PMID- 27181073 TI - [Persistent neurologic symptoms despite Viperfav((r)) antidote treatment after Vipera aspis bite : 2 cases]. PMID- 27181074 TI - Epidemiology of perioperative anaphylaxis. AB - Anaphylactic reactions may be either of immune (allergy, usually IgE-mediated, sometimes IgG-mediated) or non-immune origin. The incidence of anaphylactic reactions during anaesthesia varies between countries ranging from 1/1250 to 1/18,600 per procedure. In France, the estimated incidence of allergic reactions is 100.6 [76.2-125.3]/million procedure with a high female predominance (male: 55.4 [42.0-69.0], female: 154.9 [117.2-193.1]). The proportion of IgE-mediated allergic reactions seems to be relatively similar between countries, ranging from 50 to 60%. Substantial geographical variability regarding the different drugs or substances involved is reported. Reactions involving neuromuscular blocking agents are a major cause in several countries but are less frequently reported in the United States or Denmark. Reactions involving antibiotics, dyes or chlorhexidine are reported with a high and sometimes increasing frequency in most series. Reactions to latex are rapidly decreasing as a result of primary and secondary prevention policy. Regional differences are a strong incentive for repeated epidemiological surveys in different countries. PMID- 27181075 TI - Sjogren's syndrome in association with Crohn's disease. PMID- 27181076 TI - Body mass index and the risk of cancer incidence in patients with type 2 diabetes in Japan: Results from the National Center Diabetes Database. AB - AIMS/INTRODUCTION: Both type 2 diabetes and obesity increase the risk of some types of cancers, and underlying mechanisms are thought to be, at least in part, common. In the present study, we carried out a retrospective cohort study of the relationship between body mass index (BMI) categories and cancer development in Japanese type 2 diabetic patients. MATERIALS AND METHODS: A total of 113 incident cancers including 35 cancers whose incidence was reported to be increased by obesity (27 colorectal cancers, two breast cancers in postmenopausal women, one endometrial cancer, four renal cancers and one gallbladder cancer) were identified in 2,334 type 2 diabetic patients (1,616 men and 718 women) over an average observation period of 5.1 years. RESULTS: In men, there was no significant association between the BMI categories at the start of the observation period and the development of any cancer. In contrast, the incidence of all of the cancers in the women was significantly higher in the group with a BMI of less than 22.0 kg/m2 (hazard ratio 3.07, 95% CI 1.01-9.36). In either sex, there was no significant relationship between the BMI categories and the development of cancers whose risk is known to be increased by obesity. CONCLUSIONS: The findings of the present study were limited by the relatively small number of patients in the cohort, which posed a danger of not finding significance. However, the results suggested that obesity did not become an additional risk factor for cancer in Japanese type 2 diabetic patients. PMID- 27181078 TI - ON and OFF retinal ganglion cells differentially regulate serotonergic and GABAergic activity in the dorsal raphe nucleus. AB - The dorsal raphe nucleus (DRN), the major source of serotonergic input to the forebrain, receives excitatory input from the retina that can modulate serotonin levels and depressive-like behavior. In the Mongolian gerbil, retinal ganglion cells (RGCs) with alpha-like morphological and Y-like physiological properties innervate the DRN with ON DRN-projecting RGCs out numbering OFF DRN-projecting RGCs. The DRN neurons targeted by ON and OFF RGCs are unknown. To explore retino raphe anatomical organization, retinal afferents labeled with Cholera toxin B were examined for association with the postsynaptic protein PSD-95. Synaptic associations between retinal afferents and DRN serotonergic and GABAergic neurons were observed. To explore retino-raphe functional organization, light-evoked c fos expression was examined. Light significantly increased the number of DRN serotonergic and GABAergic cells expressing c-Fos. When ON RGCs were rendered silent while enhancing the firing rate of OFF RGCs, c-Fos expression was greatly increased in DRN serotonergic neurons suggesting that OFF DRN-projecting RGCs predominately activate serotonergic neurons whereas ON DRN-projecting RGCs mainly target GABAergic neurons. Direct glutamatergic retinal input to DRN 5-HT neurons contributes to the complex excitatory drive regulating these cells. Light, via the retinoraphe pathway can modify DRN 5-HT neuron activity which may play a role in modulating affective behavior. PMID- 27181079 TI - Prescription Drug Monitoring Programs: Ethical Issues in the Emergency Department. AB - Prescription drug monitoring programs are statewide databases available to clinicians to track prescriptions of controlled medications. These programs may provide valuable information to assess the history and use of controlled substances and contribute to clinical decisionmaking in the emergency department (ED). The widespread availability of the programs raises important ethical issues about beneficence, nonmaleficence, respect for persons, justice, confidentiality, veracity, and physician autonomy. In this article, we review the ethical issues surrounding prescription drug monitoring programs and how those issues might be addressed to ensure the proper application of this tool in the ED. Clinical decisionmaking in regard to the appropriate use of opioids and other controlled substances is complex and should take into account all relevant clinical factors, including age, sex, clinical condition, medical history, medication history and potential drug-drug interactions, history of addiction or diversion, and disease state. PMID- 27181080 TI - Effect of Educational Debt on Emergency Medicine Residents: A Qualitative Study Using Individual Interviews. AB - STUDY OBJECTIVE: In 2001, less than 20% of emergency medicine residents had more than $150,000 of educational debt. Our emergency medicine residents anecdotally reported much larger debt loads. Surveys have reported that debt affects career and life choices. Qualitative approaches are well suited to explore how and why such complex phenomena occur. We aim to gain a better understanding of how our emergency medicine residents experience debt. METHODS: We conducted individual semistructured interviews with emergency medicine residents. We collected self reported data related to educational debt and asked open-ended questions about debt influence on career choices, personal life, future plans, and financial decisions. We undertook a structured thematic analysis using a qualitative approach based in the grounded theory method. RESULTS: Median educational debt was $212,000. Six themes emerged from our analysis: (1) debt influenced career and life decisions by altering priorities; (2) residents experienced debt as a persistent source of background stress and felt powerless to change it; (3) residents made use of various techniques to negotiate debt in order to focus on day-to-day work; (4) personal debt philosophy, based on individual values and obtained from family, shaped how debt affected each individual; (5) debt had a normative effect and was acculturated in residency; and (6) residents reported a wide range of financial knowledge, but recognized its importance to career success. CONCLUSION: Our emergency medicine residents' debt experience is complex and involves multiple dimensions. Given our current understanding, simple solutions are unlikely to be effective in adequately addressing this issue. PMID- 27181081 TI - Synergistic Antiproliferative Effects of Zoledronic Acid and Fluvastatin on Human Pancreatic Cancer Cell Lines: An in Vitro Study. AB - Bisphosphonates and statins are known to have antitumor activities against different types of cancer cell lines. In the present study, we investigated the antiproliferative effects of the combination of zoledronic acid (ZOL), a bisphophosphonate, and fluvastatin (FLU), a statin, in vitro on two types of human pancreatic cancer cell lines, Mia PaCa-2 and Suit-2. The pancreatic cancer cell lines were treated with ZOL and FLU both individually and in combination to evaluate their antiproliferative effects using WST-8 cell proliferation assay. In this study, we demonstrated a potent synergistic antiproliferative effect of both drugs when used in combination in both cell lines. Moreover, we studied the molecular mechanism behind this synergistic effect, which was inhibited by the addition of the mevalonate pathway products, farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP). Furthermore, we aimed to determine the effect of ZOL and FLU combination on RhoA and Ras guanosine 5'-triphosphate (GTP) proteins. The combination induced a marked accumulation in RhoA and unprenylated Ras. GGPP and FPP reversed the increase in the amount of both proteins. These results indicated that the combination treatment impaired RhoA and Ras signaling pathway by the inhibition of geranylgeranylation and/or farnesylation. This study provides a potentially effective approach for the treatment of pancreatic cancer using a combination treatment of ZOL and FLU. PMID- 27181082 TI - Role of NOX2 in mediating doxorubicin-induced senescence in human endothelial progenitor cells. AB - Senescence exerts a great impact on both biological and functional properties of circulating endothelial progenitor cells (EPCs), especially in cardiovascular diseases where the physiological process of aging is accelerated upon clinical administration of certain drugs such as doxorubicin. EPC impairment contributes to doxorubicin-induced cardiotoxicity. Doxorubicin accelerates EPC aging, although mechanisms underlying this phenomenon remain to be fully clarified. Here we investigated if Nox2 activity is able to modulate the premature senescence induced in vitro by doxorubicin in human EPCs. Results showed that in conditioned media obtained from late EPC cultures, the levels of interleukin-6, isoprostanes and nitric oxide bioavailability were increased and reduced respectively after 3h of doxorubicin treatment. These derangements returned to physiological levels when cells were co-treated with apocynin or gp91ds-tat (antioxidant and specific Nox2 inhibitors, respectively). Accordingly, Nox2 activity resulted to be activated by doxorubicin. Importantly, we found that Nox2 inhibition reduced doxorubicin-induced EPC senescence, as indicated by a lower percentage of beta gal positive EPCs. In conclusion, Nox2 activity efficiently contributes to the mechanism of oxidative stress-induced increase in premature aging conferred by doxorubicin. The importance of modulation of Nox2 in human EPCs could reveal a useful tool to restore EPC physiological function and properties. PMID- 27181083 TI - Yeast buddies helping to unravel the complexity of neurodegenerative disorders. AB - Neurodegenerative disorders have a profound effect on the quality of life of patients and their environment. However, the development of adequate therapies requires accurate understanding of the underlying disease pathogenesis. On that account, yeast models can play an important role, as they enable the elucidation of the mechanisms leading to neurodegenerative disorders. Furthermore, by using so-called humanized yeast systems, the findings in yeast can be interpolated to humans. In this review, we will give an overview of the current body of knowledge on the use of yeast models with regard to Huntington's, Parkinson's and Alzheimer's disease. In addition to the results, obtained with the baker's yeast Saccharomyces cerevisiae, we also consider the existing literature on the less common but promising fission yeast Schizosaccharomyces pombe. PMID- 27181084 TI - Serum selenium and liposoluble vitamins in Japanese Black cows that had stillborn calves. AB - Stillbirth and dystocia are major factors that negatively affect beef production. We sought to clarify serum selenium and liposoluble vitamin levels in Japanese Black cows that gave birth to stillborn calves (stillbirth cows). Blood samples were collected from 103 stillbirth cows and 95 cows that gave birth to healthy calves (control cows). Serum levels of selenium (45.8 +/- 16.0 ng/ml) and vitamin A (73.0 +/- 24.8 IU/dl) in stillbirth cows were lower (P<0.05) than those in control cows (52.2 +/- 8.9 ng/ml and 93.3 +/- 14.8 IU/dl, respectively). Our findings suggest that appropriate serum selenium and vitamin A levels are important for calving cows. PMID- 27181085 TI - Utility of ultrasonography for diagnosis of superficial swellings in buffalo (Bubalus bubalis). AB - We studied 72 buffalo with superficial swellings in the head (n=4), neck (n=5), chest wall (n=4), abdominal wall (n=28), limbs (n=16), gluteal region (n=8), perineal region (n=6) and udder (n=1). Ultrasonographically, the swellings varied according to type, duration, content and location. The clinical use of ultrasound to assess these superficial swellings allowed diagnosis of abscesses (n=21), hematomas (n=11), hernias (n=17), bursitis (n=13), urethral diverticula (n=6) and tumors (n=4). Ultrasonography could precisely discriminate each lesion type (sensitivity, 71-100%; specificity, 75-100%; odds ratio, 1.0-8.4; Confidence Interval, 74.2-20; and P value 0.001). The specificity for ultrasonographic evaluation of superficial swellings was 100% for hernias, urethral diverticula and tumors, whilst the lowest specificity was recorded for hematomas (75%) and abscesses (92%). In conclusion, ultrasonography provides a precise, non-invasive and fast technique for the evaluation, classification and subsequent treatment of a variety of superficial swellings in buffalo. PMID- 27181086 TI - Akabane virus nonstructural protein NSm regulates viral growth and pathogenicity in a mouse model. AB - The biological function of a nonstructural protein, NSm, of Akabane virus (AKAV) is unknown. In this study, we generated a series of NSm deletion mutant viruses by reverse genetics and compared their phenotypes. The mutant in which the NSm coding region was almost completely deleted could not be rescued, suggesting that NSm plays a role in virus replication. We next generated mutant viruses possessing various partial deletions in NSm and identified several regions critical for virus infectivity. All rescued mutant viruses produced smaller plaques and grew inefficiently in cell culture, compared to the wild-type virus. Interestingly, although the pathogenicity of NSm deletion mutant viruses varied in mice depending on their deletion regions and sizes, more than half the mice died following infection with any mutant virus and the dead mice exhibited encephalitis as in wild-type virus-inoculated mice, indicating their neuroinvasiveness. Abundant viral antigens were detected in the brain tissues of dead mice, whereas appreciable antigen was not observed in those of surviving mice, suggesting a correlation between virus growth rate in the brain and neuropathogenicity in mice. We conclude that NSm affects AKAV replication in vitro as well as in vivo and that it may function as a virulence factor. PMID- 27181087 TI - Crash risk: How cycling flow can help explain crash data. AB - Crash databases are commonly queried to infer crash causation, prioritize countermeasures to prevent crashes, and evaluate safety systems. However, crash databases, which may be compiled from police and hospital records, alone cannot provide estimates of crash risk. Moreover, they fail to capture road user behavior before the crash. In Sweden, as in many other countries, crash databases are particularly sterile when it comes to bicycle crashes. In fact, not only are bicycle crashes underreported in police reports, they are also poorly documented in hospital reports. Nevertheless, these reports are irreplaceable sources of information, clearly highlighting the surprising prevalence of single-bicycle crashes and hinting at some cyclist behaviors, such as alcohol consumption, that may increase crash risk. In this study, we used exposure data from 11 roadside stations measuring cyclist flow in Gothenburg to help explain crash data and estimate risk. For instance, our results show that crash risk is greatest at night on weekends, and that this risk is larger for single-bicycle crashes than for crashes between a cyclist and another motorist. This result suggests that the population of night-cyclists on weekend nights is particularly prone to specific crash types, which may be influenced by specific contributing factors (such as alcohol), and may require specific countermeasures. Most importantly, our results demonstrate that detailed exposure data can help select, filter, aggregate, highlight, and normalize crash data to obtain a sharper view of the cycling safety problem, to achieve a more fine-tuned intervention. PMID- 27181088 TI - Renal physiology: MAGED2 mutations in transient antenatal Bartter syndrome. PMID- 27181089 TI - Disseminated intravascular coagulation in the HELLP syndrome: how much do we really know? AB - The rate of disseminated intravascular coagulation (DIC) during pregnancy varies among nations from 0.03% to 0.35%. The existing reports suggest dissimilarity in the underlying mechanisms leading to DIC during gestation. While in developing countries preeclampsia and the HELLP syndrome are prevalent causes of DIC, the leading causes in the developed countries are placental abruption and postpartum hemorrhage. In different cohort studies, DIC is reported in about 12-14% of women with preeclampsia. Nevertheless, it has been suggested that in most cases these women also had a HELLP syndrome and that the occurrence of DIC in women who had only preeclampsia without manifestations of the HELLP syndrome is rare. The aims of this review are to: (1) highlight the mechanisms leading to DIC; (2) describe the changes in the coagulation system during this complication; and; (3) discuss the diagnostic tool and treatment modalities of DIC, in women who develop a HELLP syndrome. PMID- 27181090 TI - Fulminant type 1 diabetes mellitus with anti-programmed cell death-1 therapy. AB - Anti-programmed cell death-1 (PD-1) antibodies are regarded as a risk factor for insulin-dependent diabetes mellitus as a side-effect. While a small number of cases have been reported, evidence remains limited. This is the first report of an Asian patient developing insulin-dependent diabetes during anti-PD-1 therapy. A 55-year-old euglycemic woman receiving nivolumab for malignant melanoma showed abrupt onset of ketonuria, and elevated levels of plasma glucose (580 mg/dL) and hemoglobin A1c (7.0%). Over the next 2 weeks, serum C-peptide levels fell below the limit of detection. Islet autoantibodies were negative, and the patient showed a human leukocyte antigen haplotype associated with type 1 diabetes. Anti PD-1 therapy can cause rapid onset of insulin-dependent diabetes, possibly because of inappropriate activation of T cells. Human leukocyte antigen haplotypes might be related to the onset of this disease. Physicians should be aware of this serious adverse event and carry out routine blood glucose testing during anti-PD-1 therapy. PMID- 27181091 TI - Pitfalls of tightening driving regulations for diabetic patients. AB - The regulations of driver's license for diabetic patients have been tightened in Japan and EU countries recently for public safety. However, recent literatures showed this tightened regulation may fail to achieve its purpose. So I would like to make some raise a alarm against this trend in this article. PMID- 27181092 TI - LASP1-S100A11 axis promotes colorectal cancer aggressiveness by modulating TGFbeta/Smad signaling. AB - LIM and SH3 protein 1(LASP1) can promote colorectal cancer (CRC) progression and metastasis, but the mechanism remains unclear. Here, we show that LASP1 interacts with S100 calcium binding protein A11(S100A11) and enhances its expression in CRC. LASP1-S100A11 axis is essential for TGFbeta-mediated epithelial-mesenchymal transition (EMT) and cell aggressive phenotype. Clinically, S100A11 is overexpressed in CRC tissues and localized in both the cytoplasm and the nucleus of CRC cells. Overexpression of S100A11 in cytoplasmic and nuclear subcellular compartments is associated with tumor metastasis and poor prognosis of CRC patients. Introduction of cytoplasmic and nuclear S100A11 promotes aggressive phenotypes of CRC cells in vitro as well as growth and metastasis of CRC xenografts, whereas suppressing S100A11 abrogates these effects. Furthermore, we identify flotillin-1 (FLOT1) and histone H1 as downstream factors for cytoplasmic and nuclear pathway of S100A11, which are required for LASP1-S100A11 axis mediated EMT and CRC progression. These findings indicate S100A11, combined with LASP1, plays a critical role in promoting CRC metastasis via its subcellular effectors, FLOT1 and histone H1. PMID- 27181094 TI - EFIS lecture. Immune response to tuberculosis: How to control the most successful pathogen on earth. AB - Tuberculosis (TB) remains a major health threat and general agreement exists that better control measures are needed. These include better diagnostics, drugs and vaccines. In particular, vaccines will be critical for better TB control. Based on knowledge about protective immunity against TB, a vaccine was created, VPM1002, which shows high protective efficacy and safety in experimental animal models. The vaccine has proven safe and immunogenic in human adults and neonates and is currently assessed in clinical trials in the context of HIV exposure. As a next step, a phase III efficacy trial in adults and a phase IIb efficacy trial in neonates are being planned. Biosignatures that differentially diagnose TB disease versus latent infection with high sensitivity and specificity have been designed. Most recently, a prognostic biosignature which predicts progression from latent infection to active TB has been identified. Biosignatures are not only of great value for improved diagnosis and prognosis of TB, they can also provide guidelines for better understanding of molecular mechanisms underlying disease. Accordingly, distinct biomarkers of diagnostic and prognostic value but of unknown biological function are being characterized functionally. In this way, deeper insights have been obtained on the role of type I interferon and of neutrophils in TB in experimental animal models of TB. In conclusion, clinical and basic research further supported by computational biology can complement each other in the pursuit of knowledge-based development of improved intervention measures for TB control. PMID- 27181093 TI - T-cell immune adaptor SKAP1 regulates the induction of collagen-induced arthritis in mice. AB - SKAP1 is an immune cell adaptor that couples the T-cell receptor with the 'inside out' signalling pathway for LFA-1 mediated adhesion in T-cells. A connection of SKAP1 to the regulation of an autoimmune disorder has not previously been reported. In this study, we show that Skap1-deficient (skap1-/-) mice are highly resistant to the induction of collagen-induced arthritis (CIA), both in terms of incidence or severity. Skap1-/- T-cells were characterised by a selective reduction in the presence IL-17+ (Th17) in response to CII peptide and a marked reduction of joint infiltrating T-cells in Skap1-/- mice. SKAP1 therefore represents a novel connection to Th17 producing T-cells and is new potential target in the therapeutic intervention in autoimmune and inflammatory diseases. PMID- 27181095 TI - Oral delivery of insulin via polyethylene imine-based nanoparticles for colonic release allows glycemic control in diabetic rats. AB - In this study, insulin-containing nanoparticles were loaded into pellet cores and orally administered to diabetic rats. Polyethylene imine-based nanoparticles, either placebo or loaded with insulin, were incorporated by extrusion and spheronization technology into cores that were subsequently coated with three overlapping layers and a gastroresistant film. The starting and coated systems were evaluated in vitro for their physico-technololgical characteristics, as well as disintegration and release performance. Nanoparticles-loaded cores showed homogeneous particle size distribution and shape. When a superdisintegrant and a soluble diluent were included in the composition enhanced disintegration and release performance were observed. The selected formulations, coated either with enteric or three-layer films, showed gastroresistant and release delayed behavior in vitro, respectively. The most promising formulations were finally tested for their hypoglycemic effect in diabetic rats. Only the nanoformulations loaded into the three-layer pellets were able to induce a significant hypoglycemic activity in diabetic rats. Our results suggest that this efficient activity could be attributed to a retarded release of insulin into the distal intestine, characterized by relatively low proteolytic activity and optimal absorption. PMID- 27181096 TI - Comparison of three different techniques for camera and motion control of a teleoperated robot. AB - This research aims to evaluate new methods for robot motion control and camera orientation control through the operator's head orientation in robot teleoperation tasks. Specifically, the use of head-tracking in a non-invasive way, without immersive virtual reality devices was combined and compared with classical control modes for robot movements and camera control. Three control conditions were tested: 1) a condition with classical joystick control of both the movements of the robot and the robot camera, 2) a condition where the robot movements were controlled by a joystick and the robot camera was controlled by the user head orientation, and 3) a condition where the movements of the robot were controlled by hand gestures and the robot camera was controlled by the user head orientation. Performance, workload metrics and their evolution as the participants gained experience with the system were evaluated in a series of experiments: for each participant, the metrics were recorded during four successive similar trials. Results shows that the concept of robot camera control by user head orientation has the potential of improving the intuitiveness of robot teleoperation interfaces, specifically for novice users. However, more development is needed to reach a margin of progression comparable to a classical joystick interface. PMID- 27181097 TI - Determination of Enantiomeric Distribution of Terpenes for Quality Assessment of Australian Tea Tree Oil. AB - A number of papers have appeared in recent years proposing the use of enantiomeric ratios of key monoterpenes in Australian tea tree oil (TTO) for detection of adulterated oils. There are however a range of reported values, even from exactly the same suite of authentic oils, and we address here probable reasons for these differences and stress the importance of establishing reference ratios within each laboratory based on oils of known provenance. Any biological variation in the ratio for the key terpene terpinen-4-ol has been demonstrated to be effectively unmeasurable, because the standard deviation on multiple measurements of the same oil is of the same order as that of multiple authentic oils. PMID- 27181098 TI - Interconnected Hierarchical Porous Carbon from Lignin-Derived Byproducts of Bioethanol Production for Ultra-High Performance Supercapacitors. AB - The advent of bioethanol production has generated abundant lignin-derived byproducts which contain proteins and polysaccharides. These byproducts are inapplicable for direct material applications. In this study, lignin-derived byproducts were used for the first time as carbon precursors to construct an interconnected hierarchical porous nitrogen-doped carbon (HPNC) via hydrothermal treatment and activation. The obtained HPNC exhibited favorable features for supercapacitor applications, such as hierarchical bowl-like pore structures, a large specific surface area of 2218 m(2) g(-1), a high electronic conductivity of 4.8 S cm(-1), and a nitrogen doping content of 3.4%. HPNC-based supercapacitors in a 6 M KOH aqueous electrolyte exhibited high-rate performance with a high specific capacitance of 312 F g(-1) at 1 A g(-1) and 81% retention at 80 A g(-1) as well as an excellent cyclic life of 98% initial capacitance after 20 000 cycles at 10 A g(-1). Moreover, HPNC-based supercapacitors in the ionic liquid electrolyte of EMI-BF4 displayed an enhanced energy density of 44.7 Wh kg(-1) (remaining 74% of max value) at an ultrahigh power density of 73.1 kW kg(-1). The proposed strategy may facilitate lignin utilization and lead to a green bioethanol production process. PMID- 27181099 TI - A Novel Homozygous Mutation in the KCNJ11 Gene of a Neonate with Congenital Hyperinsulinism and Successful Management with Sirolimus. AB - Congenital hyperinsulinism (CHI) is the most common cause of neonatal persistent hypoglycemia caused by mutations in nine known genes. Early diagnosis and treatment are important to prevent brain injury. The clinical presentation and response to pharmacological therapy may vary depending on the underlying pathology. Genetic analysis is important in the diagnosis, treatment, patient follow-up, and prediction of recurrence risk within families. Our patient had severe hypoglycemia and seizure following birth. His diagnostic evaluations including genetic testing confirmed CHI. He was treated with a high-glucose infusion, high-dose diazoxide, nifedipine, and glucagon infusion. A novel homozygous mutation (p.F315I) in the KCNJ11 gene, leading to diazoxide unresponsive CHI, was identified. Both parents were heterozygous for this mutation. Our patient's clinical course was complicated by severe refractory hypoglycemia; he was successfully managed with sirolimus and surgical intervention was not required. Diazoxide, nifedipine, and glucagon were discontinued gradually following sirolimus therapy. The patient was discharged at 2 months of age on low-dose octreotide and sirolimus. His outpatient clinical follow-up continues with no episodes of hypoglycemia. We present a novel homozygous p.F315I mutation in the KCNJ11 gene leading to diazoxide-unresponsive CHI in a neonate. This case illustrates the challenges associated with the diagnosis and management of CHI, as well as the successful therapy with sirolimus. PMID- 27181100 TI - The nutritive value of condensed wheat distillers solubles for cattle. AB - The chemical composition and the energy and protein value of five batches of condensed distillers solubles (CDS) originating from wheat were determined. The net energy for lactation (NEL) was derived from digestion coefficients obtained with sheep. The true protein digested in the small intestine (DVE) and the rumen degradable protein balance (OEB) were based on the rumen degradation rate (kd D ), the rumen undegradable fraction (U) and intestinal digestibility of undegraded protein (%DVBE) predicted by regression equations derived from a data set of 28 protein feeds with kd D , U and %DVBE determined in situ. The CDS is a by-product with a high, but very variable CP content (238 to 495 g/kg DM). The CP contained on average 81% amino acids, with glutamine as main component (on average 21.8% of CP) and a relatively good lysine proportion (3.0%). Further, CDS contains quite a lot of crude fat (mean+/-SD: 71+/-14 g/kg DM), glycerol (95+/-52 g/kg DM) and sugars (123+/-24 g/kg DM) resulting in a high organic matter digestibility (88.6+/-3.0%) and high NEL content (8.3+/-0.4 MJ/kg DM). The protein value showed a large variation, with DVE ranging from 122 to 244 g/kg DM and OEB from 50 to 204 g/kg DM. Wheat CDS is a rich source of minerals and trace elements with exception of calcium. PMID- 27181101 TI - Systemic features of rotavirus infection. AB - A growing body of evidence warrants a revision of the received/conventional wisdom of rotavirus infection as synonymous with acute gastroenteritis. Rotavirus vaccines have boosted our interest and knowledge of this virus, but also importantly, they may have changed the landscape of the disease. Extraintestinal spread of rotavirus is well documented, and the clinical spectrum of the disease is widening. Furthermore, the positive impact of current rotavirus vaccines in reducing seizure hospitalization rates should prompt a reassessment of the actual burden of extraintestinal manifestations of rotavirus diseases. This article discusses current knowledge of the systemic extraintestinal manifestations of rotavirus infection and their underlying mechanisms, and aims to pave the way for future clinical, public health and research questions. PMID- 27181102 TI - Anti-inflammatory role of glucose-dependent insulinotropic polypeptide in periodontitis. AB - AIMS/INTRODUCTION: The involvement of glucose-dependent insulinotropic polypeptide (GIP) on inflammation was explored in atherosclerosis and adipose tissue. Periodontal disease is a chronic inflammatory disease, and is considered one of the diabetic complications. In the present study, to examine the effect of GIP on periodontitis, we induced experimental periodontitis in glucose-dependent insulinotropic polypeptide receptor-knockout mice (GIPRKO). We also investigated the anti-inflammatory effect of GIP in a culture system. MATERIALS AND METHODS: Experimental periodontitis was induced by ligature wire in GIPRKO and C57BL/C mice. Two weeks after the ligature, immunohistological evaluation and inflammatory messenger ribonucleic acid expression in the gingiva was examined. To elucidate the role of GIP in inflammation, the effects of GIP on lipopolysaccharide-induced gene expressions in THP-1 cells were evaluated. RESULTS: Periodontitis increased inflammatory cell infiltration, macrophage accumulation and tumor necrosis factor-alpha and nitric oxide synthase gene expressions in the gingiva. Periodontitis in GIPRKO showed a marked increase of inflammatory cells in the gingivomucosal tissue. Mac-1-positive macrophages and the inflammatory gene expressions were significantly increased in periodontitis in GIPRKO compared with C57BL/C mice periodontitis. Immunohistochemical staining confirmed that GIP receptors were expressed in residual and infiltrated Mac-1 positive macrophages. The in vitro study showed that GIP suppressed lipopolysaccharide-induced tumor necrosis factor-alpha and nitric oxide synthase gene expression in a dose-dependent manner. Furthermore, the inhibitory effect of GIP on lipopolysaccharide-induced inflammatory gene expressions was at least partially through cyclic adenosine monophosphate/protein kinase A pathway. CONCLUSIONS: These results suggest the beneficial effects of GIP on periodontal disease. In diabetic patients, GIP is expected to have a direct anti-inflammatory effect on periodontitis in addition to its glucose-lowering effect. PMID- 27181105 TI - Controversy about the relationship between sulfonylurea use and cardiovascular events and mortality. AB - Among a number of classes of oral antihyperglycemic drugs, sulfonylureas (SUs) demonstrating the potential effect to reduce blood glucose level have been used in a majority of patients with type 2 diabetes for many years. The pathophysiological processes by which SUs adversely induce the risk of cardiovascular disease have not been fully clarified. We summarized about the relationship between SU use and cardiovascular events and mortality in patients with type 2 diabetes. PMID- 27181104 TI - [Hepatitis B and pregnancy. Part 2. Nine practical issues about delivery and neonatal care]. AB - In France, the hepatitis B maternal-fetal transmission prevention strategy is based on serovaccination at birth. Serum therapy is to inject 30IU/kg of anti-HBs specific immunoglobulins of human origin in the first hours of life, which in practice corresponds to 1ml or 100IU. Vaccination should also be performed during the first hours of life, and a new injection should be performed at 1month and 6months. In infants less than 32weeks and/or less than 2kg, lower vaccine response leads to prescribe an additional injection at 2months. This serovaccination reduces the risk of mother to child transmission from 57 to 4 %. The failure risk factors of serovaccination are high maternal viral load (greater than or equal to 7 log) and/or the presence of HBeAg. The delivery route does not change the risk of maternal-fetal transmission of hepatitis B when serovaccination at birth was well conducted. Likewise, breastfeeding does not change the risk of maternal-fetal transmission of hepatitis B after serovaccination. It is recommended by WHO. During labor, the pH in utero should be done only when strictly necessary, the published data do not allow to conclude on the risk of transmission. PMID- 27181103 TI - SOD2 deregulation enhances migration, invasion and has poor prognosis in salivary adenoid cystic carcinoma. AB - This study aimed to investigate the role of SOD2 in the progression and metastasis of salivary adenoid cystic carcinoma (SACC). We analyzed the expression of SOD2 in 50 SACC patients. Then, the effects and mechanism of SOD2 on cell metastasis in a pair of different metastatic potential cell lines was investigated. SOD2 was deregulated in patients with SACC. Up-regulation of SOD2 was associated with distant metastasis and reduced overall survival and disease free - survival. Compared to SACC-83 cells (lower metastasis ability), SACC-LM cells (higher metastasis ability) had higher SOD2 activity and intracellular H2O2 concentrations, and protein levels of pERK1/2 and Slug, but had similar catalase protein level and activity. In SACC-LM, reducing the expression of SOD2 by SiRNA inhibited the metastasis ability and reduced the SOD2 activities, intracellular H2O2 concentrations, and protein levels of pERK1/2 and Slug. These effects were revised in SACC-83 after SOD2 overexpression. Moreover, in SACC-83, treated with H2O2, the metastasis was enhanced accompanied by increased protein levels of pERK1/2 and Slug. We confirmed that SOD2 play an important role in the development and prognosis of SACC and SOD2-dependent production of H2O2 contributes to metastasis of SACC through the ERK-Slug signaling pathway. PMID- 27181106 TI - Sodium nitrite attenuates hypertension-in-pregnancy and blunts increases in soluble fms-like tyrosine kinase-1 and in vascular endothelial growth factor. AB - Preeclampsia is a pregnancy-associated disorder characterized by hypertension with uncertain pathogenesis. Increases in antiangiogenic soluble fms-like tyrosine kinase-1 (sFlt-1) and reductions in nitric oxide (NO) bioavailability have been observed in preeclamptic women. However, the specific mechanisms linking these detrimental changes to the hypertension-in-pregnancy are not clearly understood. In this regard, while recent findings have suggested that nitrite-derived NO formation exerts antihypertensive and antioxidant effects, no previous study has examined these responses to orally administered nitrite in hypertension-in-pregnancy. We then hypothesized restoring NO bioavailability with sodium nitrite in pregnant rats upon NO synthesis inhibition with N(omega)-nitro l-arginine methyl ester (L-NAME) attenuates hypertension and high circulating levels of sFlt-1. Number and weight of pups and placentae were recorded to assess maternal-fetal interface. Plasma sFlt-1, vascular endothelial growth factor (VEGF) and biochemical determinants of NO formation and of antioxidant function were measured. We found that sodium nitrite blunts the hypertension-in-pregnancy and restores the NO bioavailability, and concomitantly prevents the L-NAME induced high circulating sFlt-1 and VEGF levels. Also, our results suggest that nitrite-derived NO protected against reductions in litter size and placental weight caused by L-NAME, improving number of viable and resorbed fetuses and antioxidant function. Therefore, the present findings are consistent with the hypothesis that nitrite-derived NO may possibly be the driving force behind the maternal and fetal beneficial effects observed with sodium nitrite during hypertension-in-pregnancy. Certainly further investigations are required in preeclampsia, since counteracting the damages to the mother and fetal sides resulting from hypertension and elevated sFlt-1 levels may provide a great benefit in this gestational hypertensive disease. PMID- 27181108 TI - An atom probe perspective on phase separation and precipitation in duplex stainless steels. AB - Three-dimensional chemical imaging of Fe-Cr alloys showing Fe-rich (alpha)/Cr rich (alpha') phase separation is reported using atom probe tomography techniques. The extent of phase separation, i.e., amplitude and wavelength, has been quantitatively assessed using the Langer-Bar-on-Miller, proximity histogram, and autocorrelation function methods for two separate Fe-Cr alloys, designated 2101 and 2205. Although the 2101 alloy possesses a larger wavelength and amplitude after annealing at 427 degrees C for 100-10 000 h, it exhibits a lower hardness than the 2205 alloy. In addition to this phase separation, ultra-fine Ni Mn-Si-Cu-rich G-phase precipitates form at the alpha/alpha' interfaces in both alloys. For the 2101 alloy, Cu clusters act to form a nucleus, around which a Ni Mn-Si shell develops during the precipitation process. For the 2205 alloy, the Ni and Cu atoms enrich simultaneously and no core-shell chemical distribution was found. This segregation phenomenon may arise from the exact Ni/Cu ratio inside the ferrite. After annealing for 10 000 h, the number density of the G-phase within the 2205 alloy was found to be roughly one order of magnitude higher than in the 2101 alloy. The G-phase precipitates have an additional deleterious effect on the thermal embrittlement, as evaluated by the Ashby-Orowan equation, which explains the discrepancy between the hardness and the rate of phase separation with respect to annealing time (Gladman T 1999 Mater. Sci. Tech. Ser. 15 30-36). PMID- 27181107 TI - Development of passive CLARITY and immunofluorescent labelling of multiple proteins in human cerebellum: understanding mechanisms of neurodegeneration in mitochondrial disease. AB - CLARITY enables immunofluorescent labelling and imaging of large volumes of tissue to provide a better insight into the three dimensional relationship between cellular morphology and spatial interactions between different cell types. In the current study, we optimise passive CLARITY and immunofluorescent labelling of neurons and mitochondrial proteins in mouse and human brain tissues to gain further insights into mechanisms of neurodegeneration occurring in mitochondrial disease. This is the first study to utilise human cerebellum fixed in paraformaldehyde and cryoprotected in conjunction with formalin-fixed tissues opening up further avenues for use of archived tissue. We optimised hydrogel embedding and passive clearance of lipids from both mouse (n = 5) and human (n = 9) cerebellum as well as developing an immunofluorescent protocol that consistently labels different neuronal domains as well as blood vessels. In addition to visualising large structures, we were able to visualise mitochondrial proteins in passively cleared tissues to reveal respiratory chain deficiency associated with mitochondrial disease. We also demonstrate multiple use of tissues by stripping antibodies and re-probing the cerebellum. This technique allows interrogation of large volumes intact brain samples for better understanding of the complex pathological changes taking place in mitochondrial disease. PMID- 27181109 TI - Elevated circulating level of a cytokine, pancreatic-derived factor, is associated with metabolic syndrome components in a Chinese population. AB - AIMS/INTRODUCTION: Pancreatic-derived factor (PANDER) is an important factor involved in obesity, glucose intolerance and abnormal lipid metabolism in animals. Nevertheless, the relationship between PANDER and metabolic syndrome (MetS) in humans has not yet been reported. MATERIALS AND METHODS: To determinate the relationship between PANDER and MetS components, 212 individuals aged between 40 and 65 years were recruited. Fasting plasma PANDER and other variables were measured. Correlations of plasma PANDER and other variables were carried out. Plasma PANDER level was compared in participants with no metabolic components and those with any metabolic components, as well as in normal glucose tolerance, impaired glucose tolerance and diabetes mellitus participants. RESULTS: In all the participants, there were 65 participants in the no metabolic components group and 147 participants in the any metabolic components group. Plasma PANDER level was increased with the number of MetS components (P < 0.05) and correlated with metabolic score (r = 0. 529, P < 0.001). In addition, plasma PANDER significantly correlated with fasting plasma glucose (r = 0.187, P = 0.046), 2-h plasma glucose (r = 0.195, P = 0.035), homeostasis model assessment of beta-cell function (r = 0.191, P = 0.039), triglyceride (r = 0.305, P = 0.001) and high-density lipoprotein cholesterol (r = -0.333, P < 0.001). Using multivariable logistic regression analysis, circulating PANDER was associated with an increased risk ratio of impaired glucose tolerance or diabetes mellitus (odds ratio 2.22, 95% confidence interval 1.15-4.42, P = 0.018) after adjustment of the other possible confounders. CONCLUSIONS: Circulating level of PANDER in relation to the accumulation in MetS suggested that persons with elevated levels of PANDER were associated with an increased risk of metabolic syndrome. PMID- 27181110 TI - Pitavastatin improves glycated hemoglobin in patients with poorly controlled type 2 diabetes. AB - AIMS/INTRODUCTION: To investigate the effect of pitavastatin on glucose control in patients with type 2 diabetes. MATERIALS AND METHODS: Medical records of 340 patients with type 2 diabetes treated with pitavastatin or atorvastatin between 1 August 2013 and 31 May 2014 were reviewed. A total of 96 patients who had not received statins were treated with pitavastatin (N to P group). A total of 100 patients who had previously used atorvastatin were switched to pitavastatin (A to P group). A total of 144 patients continued with atorvastatin treatment. Data were collected at baseline, 3 and 6 months of treatment. Changes in glycated hemoglobin (HbA1c) level were analyzed in 222 patients who did not change their antidiabetic agent during 6 months of treatment. RESULTS: A negative correlation between baseline HbA1c and delta HbA1c at 6 months was found in the pitavastatin treated patients (N to P group: rho = -0.329, P = 0.006; A to P group: rho = 0.480, P < 0.001). The correlation remained similar after adjusting for age, body mass index, dose of pitavastatin, estimated glomerular filtration rate and high density lipoprotein cholesterol. After 6 months of treatment, the benefit of pitavastatin on HbA1c in the patients with poorly controlled diabetes was significant in both the N to P (8.1 vs 7.4%, P = 0.018) and A to P (9.7 vs 9.0%, P = 0.015) groups. CONCLUSIONS: Pitavastatin decreases HbA1c in patients with type 2 diabetes with a higher baseline HbA1c level. The benefit on HbA1c was also observed in patients with previous use of atorvastatin. PMID- 27181111 TI - Pixel-level plasmonic microcavity infrared photodetector. AB - Recently, plasmonics has been central to the manipulation of photons on the subwavelength scale, and superior infrared imagers have opened novel applications in many fields. Here, we demonstrate the first pixel-level plasmonic microcavity infrared photodetector with a single quantum well integrated between metal patches and a reflection layer. Greater than one order of magnitude enhancement of the peak responsivity has been observed. The significant improvement originates from the highly confined optical mode in the cavity, leading to a strong coupling between photons and the quantum well, resulting in the enhanced photo-electric conversion process. Such strong coupling from the localized surface plasmon mode inside the cavity is independent of incident angles, offering a unique solution to high-performance focal plane array devices. This demonstration paves the way for important infrared optoelectronic devices for sensing and imaging. PMID- 27181112 TI - Transformation from Globular to Cylindrical Mixed Micelles through Molecular Exchange that Induces Micelle Fusion. AB - Transformations between different micellar morphologies in solution induced by changes in composition, salt, or temperature are well-known phenomena; however, the understanding of the associated kinetic pathways is still limited. Especially for mixed surfactant systems, the micelles can take a very wide range of structures, depending on the surfactant packing parameter and other thermodynamic conditions. Synchrotron-based small-angle X-ray scattering (SAXS) in combination with fast mixing using a stopped-flow apparatus can give direct access to the structural kinetics on a millisecond time scale. Here, this approach is used to study the formation of cylindrical micelles after mixing two solutions with globular micelles of the nonionic surfactant dodecyl maltoside (DDM) and the anionic surfactant sodium dodecyl sulfate (SDS), respectively. Two separate processes were identified: (i) a transition in micellar shell structure, interpreted as exchange of surfactant molecules resulting in mixed globular micelles, and subsequently, (ii) fusion into larger, cylindrical structures. PMID- 27181113 TI - Synthesis and Mechanism Insight of a Peptide-Grafted Hyperbranched Polymer Nanosheet with Weak Positive Charges but Excellent Intrinsically Antibacterial Efficacy. AB - Antimicrobial resistance is an increasingly problematic issue in the world and there is a present and urgent need to develop new antimicrobial therapies without drug resistance. Antibacterial polymers are less susceptible to drug resistance but they are prone to inducing serious side effects due to high positive charge. Herein we report a peptide-grafted hyperbranched polymer which can self-assemble into unusual nanosheets with highly effective intrinsically antibacterial activity but weak positive charges (+ 6.1 mV). The hyperbranched polymer was synthesized by sequential Michael addition-based thiol-ene and free radical mediated thiol-ene reactions, and followed by ring-opening polymerization of N carboxyanhydrides (NCAs). The nanosheet structure was confirmed by transmission electron microscopy (TEM) and atomic force microscopy (AFM) studies. Furthermore, a novel "wrapping and penetrating" antibacterial mechanism of the nanosheets was revealed by TEM and it is the key to significantly decrease the positive charges but have a very low minimum inhibitory concentration (MIC) of 16 MUg mL(-1) against typical Gram-positive and Gram-negative bacteria. Overall, our synthetic strategy demonstrates a new insight for synthesizing antibacterial nanomaterials with weak positive charges. Moreover, the unique antibacterial mechanism of our nanosheets may be extended for designing next-generation antibacterial agents without drug resistance. PMID- 27181114 TI - Stimulants for impulsive violence in schizophrenia spectrum disordered women: a case series and brief review. AB - High violence prevalence is a common concern for forensic psychiatric settings. Categorizing underlying drivers of violence has helped to direct treatment and management efforts toward psychotic, predatory, and impulsively violent psychopathology. This article describes a series of cases in which clozapine provided adequate control of psychosis in women suffering schizophrenia-spectrum disorders. Nevertheless, impulsive violence remained problematic. Add-on methylphenidate was found to be safe and effective in curbing impulsive violent behavior in this select group of patients. PMID- 27181115 TI - The efficacy and safety of additional administration of tacrolimus in patients with rheumatoid arthritis who showed an inadequate response to tocilizumab. AB - OBJECTIVES: Tocilizumab (TCZ) shows good retention in patients with rheumatoid arthritis (RA), but no previous reports demonstrated hopeful treatment options against inadequate response to TCZ. Tacrolimus (TAC) has proved to show efficacy against inadequate response to tumor necrosis factor alpha inhibitors, yet its add-on effects on TCZ remain unknown. METHODS: Twenty patients with RA (17 women, age 58.6 years, disease duration 12.1 years, prior TCZ duration 2.6 years, 18 intravenous [8 mg/kg/month] and 2 subcutaneous [324 mg/month] TCZ treatments, methotrexate 6.1 mg/week [70.0%]) who showed an inadequate response to TCZ (clinical disease activity index [CDAI] >= 5.8, 18 secondary non-responders) were additionally treated with TAC (1.1 mg/day), and enrolled in this 24-week, prospective study. RESULTS: Seventeen patients (85.0%) continued the treatment for 24 weeks. Statistically significant decreases in outcome measures were as follows: disease activity score based on 28 joints with C-reactive protein (DAS28 CRP) from 3.3 at baseline to 2.1 at week 24 (p < 0.001), CDAI from 17.7 to 7.6 (p < 0.001), and serum matrix metalloproteinase-3 levels from 232.8 to 66.2 ng/ml (p < 0.001). About 15 patients (75%) achieved low disease activity or remission (DAS28-CRP <=2.7 or CDAI <=10) at week 24. CONCLUSIONS: Adding low-dose TAC to inadequate responders to TCZ may be a promising complementary treatment option. PMID- 27181116 TI - Commentary: Is There Clinical Benefit From Using a Diode or Neodymium:Yttrium Aluminum-Garnet Laser in the Treatment of Periodontitis? AB - Despite a quarter of a century of laser research, there is a persistent debate regarding the efficacy of dental lasers in the treatment of periodontitis or periodontal maintenance therapy. There are many claims and much hyperbole surrounding the use of lasers, either as a monotherapy or adjunctive to scaling and root planing, to treat periodontitis. There is little evidence that using a diode or neodymium:yttrium-aluminum-garnet laser adds clinical value over and above conventional non-surgical or surgical periodontal treatment. There is a significant need for better designed human clinical trials. Data from such trials should be analyzed according to initial probing depth and characteristics of the treated sites, such as non-molar, molar flat surfaces, and molar furcations, and evaluated for long-term post-treatment results. PMID- 27181122 TI - The legendary life of Dr. Gim Shek Ju, the founding father of the education of acupuncture and Chinese medicine in the United States. PMID- 27181121 TI - Meta-Selective CAr-H Nitration of Arenes through a Ru3(CO)12-Catalyzed Ortho Metalation Strategy. AB - The first example of transition metal-catalyzed meta-selective CAr-H nitration of arenes is described. With the use of Ru3(CO)12 as the catalyst and Cu(NO3)2.3H2O as the nitro source, a wide spectrum of arenes bearing diversified N-heterocycles or oximido as the directing groups were nitrated with meta-selectivity exclusively. Mechanism studies have demonstrated the formation of a new 18e octahedral ruthenium species as a key ortho-CAr-H metalated intermediate, which may be responsible for the subsequent meta-selective electrophilic aromatic substitution (SEAr). Moreover, this approach provides a fast-track strategy for atom/step economical synthesis of many useful pharmaceutical molecules. PMID- 27181123 TI - Interventional mechanisms of herbs or herbal extracts on renal interstitial fibrosis. AB - Renal interstitial fibrosis (RIF) is a common development in chronic renal diseases that can lead to uremia and be life-threatening. The RIF pathology has complicated extracellular and intercellular mechanisms, involving many cells and cytokines, resulting in an incomplete mechanistic understanding of the disease. Finding effective herbs or herbal extracts for prevention and treatment of RIF is crucial because current medical approaches do not reliably slow or reverse RIF. In recent years, many experts have worked to identify herbs or herbal extracts to combat RIF both in vivo and in vitro, with some success. This review attempts to summarize the possible interventional mechanisms of herbs or herbal extracts involved in protecting and reversing RIF. The authors found some herbs and their extracts that may ameliorate renal impairments through anti-inflammation, anti fibrogenesis and stabilization of extra cellular matrix. Among them, tetramethylpyrazine/ligustrazine, curcumin and polyglucoside of Tripterygium have experimentally shown good potential for improving RIF. However, conclusive evidence is still needed, especially in randomized controlled clinical trials. We expect that herbs or herbal extracts will play an important role in RIF treatment and reversal in the future. PMID- 27181124 TI - Hazards of insomnia and the effects of acupuncture treatment on insomnia. AB - Insomnia is a common disease in modern society; it is made worse by increasingly fierce competition in the workplace and elsewhere, along with rapid economic and social development. Sleep disorders can result in changes in serum biomarkers and decreased immunity, and may cause maladies such as depression and cardiac diseases, as well as many other somatic symptoms. Western medications for treating insomnia can easily lead to addiction and other adverse effects. Fortunately, acupuncture can ease the symptoms of insomnia. This review summarizes the hazards associated with insomnia and the use of acupuncture in its treatment. Furthermore, the authors introduce an effective and low-cost method of treating insomnia with acupuncture. This review indicates that insomnia poses a major threat to mental health through its effects on serum components, heart function and the immune system of patients, which may lead to other physiological disorders. Anxiety and depression are the two main negative emotions affected by insomnia. Acupuncture, which has showed effectiveness against insomnia and its complications, may be an effective and complementary method for the treatment of insomnia and associated maladies. PMID- 27181117 TI - Human infection with Strongyloides stercoralis and other related Strongyloides species. AB - The majority of the 30-100 million people infected with Strongyloides stercoralis, a soil transmitted intestinal nematode, have subclinical (or asymptomatic) infections. These infections are commonly chronic and longstanding because of the autoinfective process associated with its unique life cycle. A change in immune status can increase parasite numbers, leading to hyperinfection syndrome, dissemination, and death if unrecognized. Corticosteroid use and HTLV-1 infection are most commonly associated with the hyperinfection syndrome. Strongyloides adult parasites reside in the small intestine and induce immune responses both local and systemic that remain poorly characterized. Definitive diagnosis of S. stercoralis infection is based on stool examinations for larvae, but newer diagnostics - including new immunoassays and molecular tests - will assume primacy in the next few years. Although good treatment options exist for infection and control of this infection might be possible, S. stercoralis remains largely neglected. PMID- 27181125 TI - Knowledge, attitude and practice of patients with type 2 diabetes mellitus towards complementary and alternative medicine. AB - OBJECTIVE: The use of complementary and alternative medicine (CAM) is relatively common among patients with type 2 diabetes mellitus (T2DM) around the world. Like many other countries, Saudi Arabia has a high incidence of T2DM, and incorporates the use of CAM in its treatment. This study explores the knowledge, attitude and practice (KAP) of CAM therapies among patients with T2DM and explores the relationships between sociodemographics and the KAP of CAM modalities. METHODS: This is a hospital-based, observational, cross-sectional study that selected 302 outpatients with T2DM, from Diabetic Center of King Salman bin Abdul-Aziz Hospital, in Riyadh city, in May 2014. Patients were interviewed using a predesigned questionnaire. RESULTS: The mean age of patients was (51.6 +/- 10.6) years and 43.4% of them were males. The prevalence of CAM practices was 30.5%; 30.39% of them used herbs, 20.58% used wet cupping and 17.64% used nutritional supplements and other therapies. The factors found to predict the use of CAM therapies among patients with T2DM were: age above 51 years, unemployment and the participants+/- knowledge about the effectiveness of CAM products. CONCLUSION: This preliminary study estimated the prevalence of CAM use, revealed positive attitude towards CAM and found three significant predictors of CAM use among patients with T2DM, which is consistent with regional data. A community-based research with a larger sample that targets T2DM population is needed in Saudi Arabia. PMID- 27181126 TI - Repeated cupping manipulation temporary decreases natural killer lymphocyte frequency, activity and cytotoxicity. AB - OBJECTIVE: Elevated natural killer lymphocyte cytotoxicity (NKc) has been linked with reproductive problems in women. Here we evaluate the potential benefit of cupping therapy (CT) in reproduction-related immune responses. METHODS: This was a pilot clinical study. Participants were healthy female volunteers (n = 23) with elevated NKc, and received repeated CT 3 times over 5 d (inner pressure 40-50 kPa, 40 min; 12-15 cups). Lymphocyte subsets, NKc and NK lymphocyte activity (NKa) were measured in blood on day 0 (initial levels, before the first treatment) and days 3, 10 and 17 after the last CT treatment, using the K562 stimulated CD69 expression assay. RESULTS: As a result of CT manipulations NKa was reduced on days 3 and 10, and NK percentage was reduced on day 10. NKc was most sensitive to CT treatment, resulting in their decreased counts at 3, 10 and 17 d post CT. CT treatment decreased NKc in the majority of individuals (87%), but the magnitude of the effect was variable. Out of 23 subjects 9 (39.1%) had a 2-3 fold decrease of NKc on days 3, 10 and 17; 11 (47.8%) started to show a decrease in NKc later, or more quickly returned to base levels; and only 3 (13%) subjects displayed no effect of CT on NKc. Expectedly, no changes in T-cell subsets (CD3CD4, CD3CD8, HLADR, CD158a) were observed after CT. CONCLUSION: CT decreased NK cell numbers, their activity and cytotoxicity. Low cost, safety, non invasive nature and ease of administration make CT a promising approach for NKc down-regulation. PMID- 27181127 TI - Celastrol targets IRAKs to block Toll-like receptor 4-mediated nuclear factor kappaB activation. AB - OBJECTIVE: Celastrol has been established as a nuclear factor-kappaB (NF-kappaB) activation inhibitor; however, the exact mechanism behind this action is still unknown. Using text-mining technology, the authors predicted that interleukin-1 receptor-associated kinases (IRAKs) are potential celastrol targets, and hypothesized that targeting IRAKs might be one way that celastrol inhibits NF kappaB. This is because IRAKs are key molecules for some crucial pathways to activate NF-kappaB (e.g., the interleukin-1 receptor (IL-1R)/Toll-like receptor (TLR) superfamily). METHODS: The human hepatocellular cell line (HepG2) treated with palmitic acid (PA) was used as a model for stimulating TLR4/NF-kappaB activation, in order to observe the potential effects of celastrol in IRAK regulation and NF-kappaB inhibition. The transfection of small interfering RNA was used for down-regulating TLR4, IRAK1 and IRAK4, and the Western blot method was used to detect changes in the protein expressions. RESULTS: The results showed that celastrol could effectively inhibit PA-caused TLR4-dependent NF kappaB activation in the HepG2 cells; PA also activated IRAKs, which were inhibited by celastrol. Knocking down IRAKs abolished PA-caused NF-kappaB activation. CONCLUSION: The results for the first time show that targeting IRAKs is one way in which celastrol inhibits NF-kappaB activation. PMID- 27181128 TI - A homeopathic nosode, Hepatitis C 30 demonstrates anticancer effect against liver cancer cells in vitro by modulating telomerase and topoisomerase II activities as also by promoting apoptosis via intrinsic mitochondrial pathway. AB - OBJECTIVE: Homeopathic nosodes have seldom been scientifically validated for their anticancer effects. This study was conducted to examine if a recently developed hepatitis C nosode has demonstrable anticancer potential in cancer cells in vitro. METHODS: Anticancer effects of Hepatitis C 30C (Hep C 30), if any, were initially tested on three cancer cell lines, HepG2 (liver cancer), MCF 7 (breast cancer) and A549 (lung cancer) and one normal liver cell line WRL-68 cells and subsequently a more thorough study using further scientific protocols was undertaken on HepG2 cells (against WRL-68 cells as the normal control) as HepG2 cells showed better anticancer response than the other two. Three doses, one at 50% lethal dose (LD50) and the other two below LD50, were used on HepG2 cells subsequently. Protocols like apoptosis induction and its possible signaling mechanism were deployed using immunoblots of relevant signal proteins and confocal microscopy, with particular reference to telomerase and topoisomerase II (Top II) activities, two strong cancer biomarkers for their direct relationship with divisional activities of cells and DNAs. RESULTS: Hep C 30 induced apoptosis, caused distorted cell morphology typical of apoptotic cells, increased reactive oxygen species generation and produced increased DNA nicks. Further it enhanced pro-apototic signal proteins like Bax, cytochrome c and inhibited anti apoptotic signal proteins, Bcl-2, cytochrome c and caspase-3, changed mitochondrial membrane potential and caused externalization of phosphatidylserine. The drug also decreased expression of two cancer biomarkers, Top II and telomerase, consistent with its anticancer effect. CONCLUSION: Hep C 30 has demonstrable anticancer effects against liver cancer cells in vitro. PMID- 27181129 TI - Evaluation of the effect of acupuncture on hand pain, functional deficits and health-related quality of life in patients with rheumatoid arthritis--A study protocol for a multicenter, double-blind, randomized clinical trial. AB - BACKGROUND: Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by functional disability and pain. Although acupuncture is widely used, until now Western acupuncture studies on RA have not shown conclusive positive results. Acupuncture is regarded as a reflex therapy that has effects on the human autonomic nervous system. By establishing a traditional Chinese medicine (TCM) diagnosis first, the practitioner is able to choose acupoints according to the state of each individual patient. METHODS/DESIGN: We are interested if acupuncture, using a classical diagnostic procedure to allocate acupoints to the patient according to the Shang Han Lun theory, can be effective in relieving pain, improving hand function and increasing health-related quality of life in RA.The authors intend to harmonize TCM diagnosis according to clinical and genetic profiles. Patients with the TCM diagnosis of a so-called Turning Point syndrome will be followed up in a randomized, prospective, double-blind, placebo-controlled, multicenter and three-armed parallel-group study with a standardized treatment in order to optimize potential therapeutic effects of acupuncture on pain, strength and muscle function of patients with RA as well as the influence on inflammation and quality of life. DISCUSSION: The findings of this study will provide important clinical information about the feasibility and efficacy of acupuncture treatment for RA patients. In addition, it will explore the feasibility of further acupuncture research. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier NCT02553005. PMID- 27181131 TI - Ten-year kidney transplant survival of cyclosporine- or tacrolimus-treated patients in Brazil. AB - BACKGROUND: Cyclosporine and tacrolimus are well established immunosuppressants; however little is known about long term survival rates. The project aim was to compare 10-year graft survival and associated factors among kidney transplant patients within the Brazilian Public Health System (SUS) prescribed either immunosuppressant. METHODS: Analyze a national cohort of kidney transplant recipients within SUS. Graft loss defined by death or dialysis for more than three months. Kaplan-Meier method used to estimate cumulative probabilities of survival. Cox proportional hazards model used to evaluate factors associated with progression to graft loss. RESULTS: 13,811 patients were included, 5,887 used cyclosporine and 7,924 tacrolimus. A higher risk of graft loss was associated with tacrolimus, a deceased donor, additional years of age, median period of dialysis greater than 47 months, diagnosis of diabetes as the primary cause of chronic kidney disease and transplantation between 2005 and 2009. CONCLUSIONS: Among other factors, tacrolimus-based regimens were associated with worse graft survival. PMID- 27181132 TI - Predictive role of host constitutive variants in neoadjuvant therapy of esophageal cancer. AB - Chemoradiotherapy followed by surgery is at present the standard therapeutic approach for esophageal cancer (EC) in patients with resectable tumor. However, response to neoadjuvant therapy is characterized by a strong interpatient variability, and the identification of markers predictive of outcome is mandatory. In this review, taking into account the currently available literature, we report the impact that host genetic variables can have on EC neoadjuvant therapy. We mainly focused on the gene variants involved in the pharmacokinetics and pharmacodynamics of the common chemotherapeutic drugs used to treat EC patients, commented on the weakness of the present knowledge, and discussed the future strategies to achieve a more personalized and effective EC treatment. PMID- 27181133 TI - Trihaloethenes as versatile building blocks for organic synthesis. AB - This review highlights the chemistry of trihaloethene building blocks with a special focus on commercially available 1,1,2-trichloroethene. The topics surveyed herein include the use of trihaloethenes as C2-building blocks for transition metal-catalyzed coupling reactions, addition, elimination and cycloaddition reactions as well as natural product syntheses. PMID- 27181130 TI - Adjunctive acupuncture for pain and symptom management in the inpatient setting: protocol for a pilot hybrid effectiveness-implementation study. AB - BACKGROUND: Effective pain management among hospitalized patients is an important aspect of providing quality care and achieving optimal clinical outcomes and patient satisfaction. Common pharmacologic approaches for pain, though effective, have serious side effects and are not appropriate for all inpatients. Findings from randomized controlled trials (RCTs) support the efficacy of acupuncture for many symptoms relevant to inpatients including postoperative pain, cancer-related pain, nausea and vomiting, and withdrawal from narcotic use. However, the extent to which findings from RCTs translate to real-world implementation of acupuncture in typical hospital settings is unknown. METHODS/DESIGN: In partnership with the launch of a clinical program offering acupuncture services to inpatients at the University of California San Francisco's Mount Zion Hospital, we are conducting a pilot study using a hybrid effectiveness-implementation design to: (1) assess the effectiveness of acupuncture to manage pain and other symptoms and improve patient satisfaction; and (2) evaluate the barriers and facilitators to implementing an on-going acupuncture service for inpatients. During a two-month pre-randomization phase, we evaluated and adapted clinical scheduling and treatment protocols with acupuncturists and hospital providers and pretested study procedures including enrollment, consent, and data collection. During a six month randomization phase, we used a two-tiered consent process in which inpatients were first consented into a study of symptom management, randomized to be offered acupuncture, and consented for acupuncture if they accepted. We are also conducting in-depth interviews and focus groups to assess evidence, context, and facilitators of key provider and hospital administration stakeholders. DISCUSSION: Effectiveness research in "real-world" practice settings is needed to inform clinical decision-making and guide implementation of evidence-based acupuncture practices. To successfully provide clinical acupuncture services and maintain a rigorous research design, practice-based trials of acupuncture require careful planning and attention to setting-specific, contextual factors. TRIAL REGISTRATION: This trial has been registered in ClinicalTrials.gov. The identifier is NCT01988194, registered on November 5, 2013. PMID- 27181134 TI - Differentiating hand-foot syndrome from tinea in patients receiving chemotherapy. PMID- 27181135 TI - Chemical composition and vascular and intestinal smooth muscle relaxant effects of the essential oil from Psidium guajava fruit. AB - CONTEXT: Psidium guajava L. (Myrtaceae) is widely used in traditional medicine for the treatment of various ailments including cardiovascular and gastrointestinal disorders. OBJECTIVES: The current study investigated the chemical composition and cardiovascular and gastrointestinal effects of the essential oil of P. guajava. MATERIALS AND METHODS: The chemical composition of the essential oil was investigated using gas chromatography-mass spectrometry (GC MS) technique. The biological activity of the essential oil was tested on rabbit aorta and jejunum. All changes in isometric tension were recorded through a force transducer coupled with a bridge amplifier data acquisition system. RESULTS AND DISCUSSION: GC-MS analysis showed the presence of butanoic acid methyl ester, 3 methyl glutaric anhydride, 1-butanol, 3-hexenal, cinnamyl alcohol, 1-hexanol and hexane as the major components. In isolated rabbit aorta preparations, the essential oil showed vasorelaxation at doses of 3-10 mg/mL against high K+ and phenylephrine pre-contractions with EC50 values of 5.52 (5-6.04) and 6.23 mg/mL (5.0-7.46). The essential oil inhibited spontaneous and high K+ induced contractions in isolated rabbit jejunum with EC50 values of 0.84 (0.3-1.38) and 0.71 mg/mL (0.3-1.12) and shifted Ca + 2 concentration curves to the right, similar to verapamil, suggesting spasmolytic activity mediated possibly through Ca + 2 channel blockade. CONCLUSIONS: In summary, the data indicated the presence of seven different phytoconstituents in the essential oil of P. guajava and calcium channel blocking activity, which provides a pharmacological base to the traditional use of P. guajava in cardiovascular and gastrointestinal disorders. Further studies are suggested to explore the molecular nature of these effects. PMID- 27181136 TI - Fetal scalp blood lactate during second stage of labor: determination of reference values and impact of obstetrical interventions. AB - OBJECTIVE: To determine the reference interval of fetal scalp blood lactate during second stage of labor. MATERIAL: Two hundred and fifty-three women in first stage of labor with a reassuring CTG were asked for permission to sample fetal scalp blood during second stage. RESULTS: In cases with reassuring CTG and five minute Apgar score >=9, the mean lactate value (+/-2 SD) was 2.5 mmol/L (lower limit 1.1, higher limit 5.2). The lactate concentration was significantly higher among nulliparous and in cases with use of epidural or oxytocin (p <0.001). There was a moderate positive correlation between scalp lactate values and active pushing time. When parity, epidural, oxytocin and active pushing time were analyzed together, they had equal influence on lactate values (p <0.001). Higher lactate values were associated with intermediate/pathological CTG compared to normal CTG (p <0.001). There was no correlation to gestational age or birthweight (p = 0.72, respectively 0.43). CONCLUSIONS: The reference interval of fetal scalp lactate during second stage is 1.1-5.2 mmol/L. Parity, use of epidural or oxytocin and the duration of pushing are associated to increased lactate concentration; however, we could not demonstrate any correlation to advancing gestational age or birthweight. PMID- 27181137 TI - Enantiopure and racemic radical-cation salts of B(malate)2(-) anions with BEDT TTF. AB - We have synthesized the first examples of radical-cation salts of BEDT-TTF with chiral borate anions, [B(malate)2](-), prepared from either enantiopure or racemic bidentate malate ligands. In the former case only one of two diastereoisomers of the borate anion is incorporated, while for the hydrated racemic salt one racemic pair of borate anions containing a R and a S malate ligand is incorporated. Their conducting and magnetic properties are reported. The tight-binding band calculation indicates that the chiral salt has an effective half-filled flat band, which is likely to be caused by the chiral structural feature. PMID- 27181158 TI - The remarkable ability of anions to bind dihydrogen. AB - The structural features and hydrogen binding affinity of anions F(-), Cl(-), Br( ), OH(-), NH2(-), NO2(-), CN(-), and ClO(-) have been explored at the CCSD(T)/aug cc-pVTZ//CCSD/6-311++G(d,p) level of coupled cluster theory and the M06L/6 311++G(d,p) level of density functional theory along with a two-point extrapolation to the complete basis set limit and a benchmark study at CCSD(T) and MP2 levels. The coupled cluster, MP2 and DFT methods yield comparable results and show that anions have very high capacity to store hydrogen as the weight percent of H2 in the highest H2-coordinated state of F(-), Cl(-), Br(-), OH(-), NH2(-), NO2(-), CN(-), and ClO(-) is 56.0, 47.6, 33.5, 64.0, 65.4, 41.2, 55.4, and 40.0 wt%, respectively. The CCSD(T)/aug-cc-pVTZ//CCSD/6-311++G(d,p) results are presented for anions coordinated with up to nine or ten H2 molecules, while up to the entire first coordination shell is computed using the M06L method which revealed H2 coordination numbers of 12, 16, 20, 15, 15, 16, 16, and 17, respectively, for F(-), Cl(-), Br(-), OH(-), NH2(-), NO2(-), CN(-), and ClO(-). An increase in the total interaction energy (Eint) and a decrease in the interaction energy per H2 molecule (Eint/H2) with an increase in the number of coordinated H2 molecules are observed. However, the decrease in Eint/H2 is very less and even in the highest coordinated anions, substantially good values of Eint/H2 are observed, viz. 4.24, 2.59, 2.09, 3.32, 3.07, 2.36, 2.31, and 2.63 kcal mol(-1) for F(-), Cl(-), Br(-), OH(-), NH2(-), NO2(-), CN(-), and ClO(-), respectively, which are comparable with the values obtained for complexes with lesser H2 coordination. The stability of the complexes is attributed to the formation of a large number of non-covalent X(-)H bonds as revealed by the identification of bond critical points in the quantum theory of atoms in molecules (QTAIM) analysis. Further, critical features of molecular electrostatic potential (MESP) have been used to correlate the stability of X(-)(H2)n complexes with the charge delocalization in the complexes. These results show that anions have a remarkable ability to bind with a large number of hydrogen molecules and this property can be utilized for the development of novel salt systems for hydrogen storage. PMID- 27181161 TI - Strong Electrostatic Interactions Lead to Entropically Favorable Binding of Peptides to Charged Surfaces. AB - Thermodynamic analyses can provide key insights into the origins of protein self assembly on surfaces, protein function, and protein stability. However, obtaining quantitative measurements of thermodynamic observables from unbiased classical simulations of peptide or protein adsorption is challenging because of sampling limitations brought on by strong biomolecule/surface binding forces as well as time scale limitations. We used the parallel tempering metadynamics in the well tempered ensemble (PTMetaD-WTE) enhanced sampling method to study the adsorption behavior and thermodynamics of several explicitly solvated model peptide adsorption systems, providing new molecular-level insight into the biomolecule adsorption process. Specifically studied were peptides LKalpha14 and LKbeta15 and trpcage miniprotein adsorbing onto a charged, hydrophilic self-assembled monolayer surface functionalized with a carboxylic acid/carboxylate headgroup and a neutral, hydrophobic methyl-terminated self-assembled monolayer surface. Binding free energies were calculated as a function of temperature for each system and decomposed into their respective energetic and entropic contributions. We investigated how specific interfacial features such as peptide/surface electrostatic interactions and surface-bound ion content affect the thermodynamic landscape of adsorption and lead to differences in surface-bound conformations of the peptides. Results show that upon adsorption to the charged surface, configurational entropy gains of the released solvent molecules dominate the configurational entropy losses of the bound peptide. This behavior leads to an apparent increase in overall system entropy upon binding and therefore to the surprising and seemingly nonphysical result of an apparent increased binding free energy at elevated temperatures. Opposite effects and conclusions are found for the neutral surface. Additional simulations demonstrate that by adjusting the ionic strength of the solution, results that show the expected physical behavior, i.e., peptide binding strength that decreases with increasing temperature or is independent of temperature altogether, can be recovered on the charged surface. On the basis of this analysis, an overall free energy for the entire thermodynamic cycle for peptide adsorption on charged surfaces is constructed and validated with independent simulations. PMID- 27181160 TI - Intrinsic quantum spin Hall and anomalous Hall effects in h-Sb/Bi epitaxial growth on a ferromagnetic MnO2 thin film. AB - Exploring a two-dimensional intrinsic quantum spin Hall state with a large band gap as well as an anomalous Hall state in realizable materials is one of the most fundamental and important goals for future applications in spintronics, valleytronics, and quantum computing. Here, by combining first-principles calculations with a tight-binding model, we predict that Sb or Bi can epitaxially grow on a stable and ferromagnetic MnO2 thin film substrate, forming a flat honeycomb sheet. The flatness of Sb or Bi provides an opportunity for the existence of Dirac points in the Brillouin zone, with its position effectively tuned by surface hydrogenation. The Dirac points in spin up and spin down channels split due to the proximity effects induced by MnO2. In the presence of both intrinsic and Rashba spin-orbit coupling, we find two band gaps exhibiting a large band gap quantum spin Hall state and a nearly quantized anomalous Hall state which can be tuned by adjusting the Fermi level. Our findings provide an efficient way to realize both quantized intrinsic spin Hall conductivity and anomalous Hall conductivity in a single material. PMID- 27181162 TI - Solvent effects on modulus of poly(propylene oxide)-based organogels as measured by cavitation rheology. AB - A series of novel organogels were synthesized from poly(propylene oxide) (PPO) functionalized with main chain urea moieties which provided rapid gelation and high moduli in a variety of solvents. Three different molecular weight PPOs were used in this study: 430, 2000, and 4000 g mol(-1), each with alpha,omega-amino end groups. Four urea groups were introduced into the main chain by reaction with hexamethylene diisocyanate followed by subsequent reaction with a monofunctional alkyl or aromatic amine. This PPO/urea gelator was found to form gels in carbon tetrachloride, chloroform, dichloromethane, toluene, ethyl acetate, and tetrahydrofuran. Among these, carbon tetrachloride and toluene were found to be the best solvents for this system, resulting in perfectly clear gels with high moduli at low mass fraction for PPO-2000 systems. Flory-Huggins polymer-solvent interaction parameter, chi, was found to be a useful indicator of gel quality for these systems, with chiCCl4/PPO-2000 < 0.5 and chitoluene/PPO-2000~ 0.5. Systems with chi parameters >0.5 were found to form low moduli gels, indicating that for these systems, polymer-solvent interaction parameters can be a useful predictor of gel quality in different solvent systems. PMID- 27181159 TI - A genetic variant in proximity to the gene LYPLAL1 is associated with lower hunger feelings and increased weight loss following Roux-en-Y gastric bypass surgery. AB - OBJECTIVE: Bariatric surgery is the most efficient treatment of severe obesity. We investigated to what extent BMI- or waist-hip ratio (WHR)-related genetic variants are associated with excess BMI loss (EBMIL) two years after Roux-en-Y gastric bypass (RYGB) surgery, and elucidated the affected biological pathways. METHODS: Two-hundred fifty-one obese patients (age: 43 +/- 10.7, preoperative BMI: 45.1 +/- 6.1 kg/m(2), 186 women) underwent RYGB surgery and were followed up after two years with regard to BMI. Patients were genotyped for 32 single nucleotide polymorphisms (SNPs) that were investigated with regard to their impact on response to RYGB and preoperatively measured Three Factor Eating Questionnaire (TFEQ) scores. RESULTS: Homozygous T carriers of the SNP rs4846567 in proximity to the Lysophospholipase-like 1 (LYPLAL1) gene showed a 7% higher EBMIL compared to wild-type and heterozygous carriers (p = 0.031). TT-allele carriers showed furthermore lower scores for Hunger (74%, p < 0.001), lower Disinhibition (53%, p < 0.001), and higher Cognitive restraint (21%, p = 0.017) than GG/GT carriers in the TFEQ. Patients within the lowest quartile of Hunger scores had a 32% greater EBMIL compared to patients in the highest quartile (p < 0.001). CONCLUSION: The LYPLAL1 genotype is associated with differences in eating behavior and loss of extensive body weight following RYGB surgery. Genotyping and the use of eating behavior-related questionnaires may help to estimate the RYGB associated therapy success. PMID- 27181163 TI - Safety evaluation and antihyperlipidemia effect of aqueous extracts from fermented puerh tea. AB - Fermented puerh tea, having undergone a long period of secondary oxidization and fermentation, has become more and more popular in recent years. In the present paper, a safety evaluation of aqueous extracts from fermented puerh tea (EFPT) was performed, including an oral acute toxicity study in rats and mice, mutation tests, a mouse micronucleus test, mouse sperm abnormality test and a 30 day feeding study in rats. Meanwhile, the antihyperlipidemia effect of EFPT was investigated as well. It was found that the oral maximum tolerated dose of EFPT was more than 10.0 g per kg body weight both in rats and mice. And it had no mutagenicity as judged by negative experimental results of the mutation test. No abnormal symptoms, clinical signs or deaths have been found in rats in each group throughout the experiments. In addition, EFPT in this study showed certain effects on hyperlipidemia. PMID- 27181164 TI - In-stem thiazole orange reveals the same triplex intermediate for pH and thermal unfolding of i-motifs. AB - The unfolding pathway of human telomeric i-motifs was monitored by both monomer and exciplex fluorescence of in-stem thiazole orange. A uniform triplex intermediate was observed upon unfolding i-motifs against either pH or thermal denaturation. PMID- 27181165 TI - Pharmacologic Approaches to Weight Management: Recent Gains and Shortfalls in Combating Obesity. AB - Obesity is a growing epidemic in the USA with over one third of adults presently classified as obese. Obesity-related comorbidities include many leading causes of preventable death such as heart disease, stroke, type 2 diabetes, and certain types of cancer. Modest weight loss of 5-10 % of body weight is sufficient to produce clinically relevant improvements in cardiovascular disease risk factors among patients with overweight and obesity. Until recently, there were limited pharmacologic options approved by the Food and Drug Administration to treat obesity. Phentermine/topiramate ER and lorcaserin were approved in 2012, and naltrexone SR/bupropion SR and liraglutide 3.0 mg were approved in 2014. This article reviews recent literature in the field of Obesity Medicine and highlights important findings from clinical trials. Future directions in the pharmacologic management of obesity are presented along with new diabetes medications that promote weight loss and reduce cardiovascular mortality. PMID- 27181167 TI - Design and fabrication of clustered rugged ZnO nanotube films with condensate microdrop self-propelling function. AB - We design and fabricate a type of condensate microdrop self-propelling (CMDSP) clustered rugged nanotube film, which is achieved by two-step electrodeposition and low-surface-energy silane modification. This work offers an avenue for developing CMDSP surfaces with self-cleaning, antifrosting, and antidewing functions. PMID- 27181166 TI - Impaired Nitric Oxide Mediated Vasodilation In The Peripheral Circulation In The R6/2 Mouse Model Of Huntington's Disease. AB - Recent evidence shows that the Huntington's disease (HD) extends beyond the nervous system to other sites, including the cardiovascular system. Further, the cardiovascular pathology pre-dates neurological decline, however the mechanisms involved remain unclear. We investigated in the R6/2 mouse model of HD nitric oxide (NO) dependent and independent endothelial mechanisms. Femoral artery reactivity was determined by wire myography in wild type (WT) and R6/2 mice at 12 and 16 weeks of adulthood. WT mice showed increased endothelial relaxation between 12 and 16 weeks (Rmax: 72 +/- 7% vs. 97 +/- 13%, P < 0.05). In contrast, R6/2 mice showed enhanced endothelial relaxation already by 12 weeks (Rmax at 12w: 72 +/- 7% vs. 94 +/- 5%, WT vs. R6/2, P < 0.05) that declined by 16 weeks compared with WT mice (Rmax at 16w: 97 +/- 13% vs. 68 +/- 7%, WT vs. R6/2, P < 0.05). In WT mice, the increase in femoral relaxation between 12 and 16 weeks was due to enhanced NO dependent mechanisms. By 16 weeks of adult age, the R6/2 mouse developed overt endothelial dysfunction due to an inability to increase NO dependent vasodilation. The data add to the growing literature of non-neural manifestations of HD and implicate NO depletion as a key mechanism underlying the HD pathophysiology in the peripheral vasculature. PMID- 27181168 TI - Calcitriol prevents inflammatory gene expression in macrovascular endothelial cells. AB - BACKGROUND: Calcitriol (vitamin D) supplementation has been proposed for therapeutical use in vascular diseases due to its immunomodulatory activity, preventing inflammation and promoting angiogenesis. In the present study, we hypothesised whether calcitriol downregulates pro-inflammatory gene expression without affecting angiogenesis and anti-inflammatory gene expression in LPS induced endothelial cells. METHOD: In order to evaluate the effect of calcitriol in suppressing inflammatory gene expression in the endothelium, endothelial cells were exposed to the physiological concentration of calcitriol followed by stimulation with lipopolysaccharide (LPS). Gene expression of interleukin (IL) 1beta, Transforming Growth Factor (TGF)-beta, Human beta-defensin (HBD)-2, angiogenin (ANG) and cathelicidin (LL-37) were quantified by quantitative polymerase chain reaction. RESULTS: The results from six independent experiments conducted in duplicate, showed that calcitriol decreased IL-1beta (p < 0.01) and HBD-2 expression (p < 0.01) when compared to non-treated cells. However, calcitriol treatment had no effect on TGF-beta, ANG and LL-37 gene expression. CONCLUSION: Calcitriol prevents inflammatory gene expression, but does not affect expression of angiogenic genes in endothelial cells, which suggest the potential use of calcitriol to prevent endothelial activation through the downregulation of IL-1beta and HBD-2. PMID- 27181169 TI - Preliminary feasibility and modelling of a liquid matrix Dictyostelium discoideum virulence assay for Pseudomonas aeruginosa. AB - OBJECTIVES: To develop and determine the feasibility of using a liquid matrix adaptation of the Dictyostelium discoideum bacterial virulence assay by testing on well-characterised clinical and environmental isolates of Pseudomonas aeruginosa. MATERIALS AND METHODS: Axenic AX2 D. discoideum were co-cultured with clinical and environmental isolates of P. aeruginosa in costar 24-well tissue culture plates for 24 h. A P. aeruginosa PAO1 positive control was tested in biological quintuplicate. Wells were then inspected using an inverted microscope and the degree of cytotoxic changes (sparse growth compared to control combined with rounding of cells and cytoplasmic shrinkage) on the D. discoideum cells was observed. A Klebsiella aerogenes negative control was included with each assay series. RESULTS: Sixty-five clinical and 20 environmental P. aeruginosa isolates were tested in the model. Cystic fibrosis respiratory isolates were found to be significantly (P < 0.05) less cytotoxic than P. aeruginosa from other sources. Limitations attached to the funding of this paper did not allow validation against previously employed models or animal models. DISCUSSION: A liquid matrix D. discoideum model for the analysis of P. aeruginosa virulence in a eukaryotic host is feasible, but further validation of the model is required before it may be employed in routine setting. PMID- 27181170 TI - Serum TGF-beta1 in patients with acute myocardial infarction. PMID- 27181171 TI - Thyroid and parathyroid hormones in benign prostatic hyperplasia. PMID- 27181172 TI - Molecular identification and characterisation of catalase and catalase-like protein genes in urease-positive thermophilic Campylobacter (UPTC). AB - BACKGROUND: Thermophilic Campylobacter are important bacterial pathogens of foodborne diseases worldwide. These organisms' physiology requires a microaerophilic atmosphere. To date, little is known about the protective catalase mechanism in urease-positive thermophilic campylobacters (UPTC); hence, it was the aim of this study to identify and characterise catalase and catalase like protein genes in these organisms. MATERIALS AND METHODS: Catalase (katA) and catalase (Kat)-like protein genes from the Japanese UPTC CF89-12 strain were molecularly analysed and compared with C. lari RM2100 and other C. lari and thermophilic Campylobacter reference isolates. RESULTS: A possible open reading frame of 1,422 base pairs, predicted to encode a peptide of 474 amino acid residues, with calculated molecular weight of 52.7 kilo Daltons for katA, was identified within UPTC CF89-12. A probable ribosome binding site, two putative promoters and a putative rho-independent transcription terminator were also identified within katA. A similar katA cluster also existed in the C. lari RM2100 strain, except that this strain carries no DcuB genes. However, the Kat-like protein gene or any other homologue(s) were never identified in the C. lari RM2100 strain, or in C. jejuni and C. upsaliensis. CONCLUSIONS: This study demonstrates the presence of catalase/catalase-like protein genes in UPTC organisms. These findings are significant in that they suggest that UPTC organisms have the protective genetic capability of helping protect the organisms from toxic oxygen stress, which may help them to survive in physiologically harsh environments, both within human and animal hosts, as well as in the natural environment. PMID- 27181173 TI - Identification of minor chromosomal defects causing abnormal foetus and spontaneous abortions. AB - BACKGROUND: Chromosomal abnormalities are the most common cause of recurrent abortions and miscarriages (RAM), but micro-variations on chromosomes causing RAM have never been previously studied. Single nucleotide polymorphisms (SNPs) are the single nucleotide variations frequently present at genome with the density of at least one common (>20% allele frequency) SNP per kilobase pair. It has already been reported that SNP array examination for chromosomal abnormalities has better performance than the conventional cytogenetic karyotyping. METHODS: We applied SNP array to detect the chromosomal defects in 80 placental villi and foetal tissues of abnormal foetus and spontaneous abortions. RESULTS: The analyses of data revealed that total 52.5% (42/80) cases were found to have chromosomal abnormalities. The trisomies were most commonly found 26/42 (61.9%) in current samples. Total 8/42 (19.1%) cases were found to have other structural aberrations including translocations in 2/8 (25%), duplications and deletions in 3/8 (37.5%) cases, respectively. SNP analysis also successfully detected triploidy 69,XXX and tetraploidy 92,XXXY. Total 12/80 cases were performed by cytogenetic karyotyping and results were compared with SNP data. Total 5/12 (41.7%) cases were found to have same findings with SNP data while results of 2/12 (16.7%) cases had partial similarity between both techniques. Four cases were declared as karyotypically normal (46,XY or 46,XX) by cytogenetic examination, but later on these four cases were found to have small chromosomal variation which could be the cause of RAM in women. CONCLUSION: Therefore, we conclude that use of a high-density SNP platform in diagnosis can give better understanding of molecular causes of pregnancy loss and foetal abnormalities. PMID- 27181174 TI - Antimicrobial resistance in cystic fibrosis isolates of Haemophilus influenzae. PMID- 27181175 TI - Aseptic meningitis after measles-mumps-rubella (MMR) vaccination. PMID- 27181176 TI - Cervical lymph node thyroglobulin measurement in washout of fine-needle aspirates for diagnosis of papillary thyroid cancer metastases. AB - BACKGROUND: Patients with papillary thyroid cancer (PTC) and enlarged cervical lymph nodes (CLNs) are usually assessed by fine-needle aspiration biopsy cytology (FNAB-C). Thyroglobulin (Tg) is frequently detected in washout of fine-needle aspirates (FNA) of these lymph nodes. The aim of this study was to evaluate the accuracy of the measurement of FNAB-Tg in the washout of FNAB in combination with FNAB-C to detect CLN metastases in PTC. METHODS: We retrospectively evaluated 163 surgically proven CLNs. Ultrasound-guided FNAB-C and FNAB-Tg measurements were performed and the ultrasound features were evaluated. RESULTS: The sensitivity, specificity and accuracy of FNAB-C, FNAB-Tg and FNAB-C/FNAB-Tg in diagnosis of metastatic CLNs were 85.7, 87.8 and 71.6%, were 80.5, 87 and 82.8% and were 97.1, 96.3 and 95.7%, respectively. The diagnostic sensitivity, specificity and accuracy of FNAB-C/FNAB-Tg for metastatic CLNs was significantly higher than that of FNAB-C or FNAB-Tg alone (p < 0.01). CONCLUSION: Combined US-guided FNAB-C and FNAB-Tg can improve the accuracy for diagnosis of metastatic CLNs in patients with PTC. PMID- 27181177 TI - Ab initio molecular dynamics investigation of structural, dynamic and spectroscopic aspects of Se(vi) species in the aqueous environment. AB - Microscopic investigation of solvation of selenic acid (H2SeO4) in the aqueous environment has been carried out using the Car-Parrinello molecular dynamics simulation technique. The species deprotonates to HSeO4(-) in a few picoseconds owing to its low pKa1 value of -3.0. A dynamic equilibrium between HSeO4(-) and SeO4(2-), is observed in qualitative agreement with the reported pKa2 value of 1.70. The governing deprotonation mechanism and the structural and dynamic evolutions of the system, particularly the nature of hydrogen bonding, their strengths and lifetimes are investigated comprehensively. A comparison of the vibrational spectra of the species recorded in the gas phase and in the aqueous environment provides further insights on the nature of the interaction between the solute species and water. The results are in good agreement with the available experimental data and other recent computational studies. PMID- 27181178 TI - A dynamic course of T cell defects in individuals at risk for mood disorders. AB - OBJECTIVES: T cell abnormalities have been repeatedly reported in adult patients with mood disorders, suggesting a role of these cells in the pathogenesis of these disorders. In the present study, we explored the dynamics of circulating T cell subsets over time in a population at high familial risk for developing a mood disorder. METHODS: Children of a parent with bipolar disorder (bipolar offspring, N=140) were assessed at three time-points: adolescence, young adulthood and adulthood. We carried out a detailed fluorescence-activated cell sorting (FACS) analysis to determine various T cell subsets from frozen stored peripheral blood mononuclear cells of bipolar offspring and age- and gender matched healthy controls at each time-point. RESULTS: Throughout the period of observation reduced levels of CD3+ and CD3+ CD4+ T cells were observed. In bipolar offspring Th1, Th2, Th17 and natural T regulatory cells (Tregs) followed a dynamic course over time with reduced levels of Tregs in adolescence and a reduced relative number of Th1, Th17 cells in young adulthood. In post hoc analysis Tregs were inversely associated with the pro-inflammatory monocyte state determined previously (rs=-0.220, p=0.001). Significant associations between T cell subset abnormalities and psychopathology such as mood disorders were not found. CONCLUSIONS: A subtle partial T cell defect was present in bipolar offspring from adolescence through adulthood. Within this defect the dynamic change of inflammatory and regulatory T cell subsets suggests a high inflammatory state during adolescence, a reduced inflammatory state during young adulthood and a virtually normalized state at adulthood. PMID- 27181179 TI - Effect of recombinant erythropoietin on inflammatory markers in patients with affective disorders: A randomised controlled study. AB - AIM: This study investigated the effect of repeated infusions of recombinant human erythropoietin (EPO) on markers of inflammation in patients with affective disorders and whether any changes in inflammatory markers were associated with improvements on verbal memory. METHODS: In total, 83 patients were recruited: 40 currently depressed patients with treatment-resistant depression (TRD) (Hamilton Depression Rating Scale-17 items (HDRS-17) score >17) (sub-study 1) and 43 patients with bipolar disorder (BD) in partial remission (HDRS-17 and Young Mania Rating Scale (YMRS)?14) (sub-study 2). In both sub-studies, patients were randomised in a double-blind, parallel-group design to receive eight weekly intravenous infusions of EPO (Eprex; 40,000IU/ml) or saline (0.9% NaCl). Plasma concentrations of interleukin 6 (IL-6), interleukin 18 (IL-18) and high sensitive c-reactive protein (hsCRP) were measured at week 1 (baseline) and weeks 5, 9 and 14. HDRS-17 and neuropsychological function was assessed at weeks 1, 9 and 14 using a test battery including the RAVLT Auditory Verbal Learning Test (primary depression and primary cognition outcomes in the original trial). RESULTS: EPO had no cumulative effect on plasma levels of IL-6 or IL-18 but increased hsCRP levels in patients with TRD (mean+/-SD change in ng/L: EPO: 0.43+/-1.64; Saline: 0.90+/-2.43; F(1,39)=4.78, p=0.04). EPO had no effects on inflammatory markers in BD. There was no correlation between change in inflammatory markers and change in verbal memory. CONCLUSIONS: Repeated EPO infusions had no effect on IL-6 and IL 18 levels but produced a modest increase in hsCRP levels in patients with TRD. Changes over time in inflammatory markers were not correlated with changes in cognition suggesting that modulation of the inflammatory pathway is not a putative mechanism of the EPO-associated improvement of cognition in affective disorders. PMID- 27181181 TI - Therapeutic inertia or individualization? Delay in clinical management of type 2 diabetes mellitus. PMID- 27181180 TI - Associations between cytokines, endocrine stress response, and gastrointestinal symptoms in autism spectrum disorder. AB - Many children and adolescents with autism spectrum disorder (ASD) have significant gastrointestinal (GI) symptoms, but the etiology is currently unknown. Some individuals with ASD show altered reactivity to stress and altered immune markers relative to typically-developing individuals, particularly stress responsive cytokines including tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6). Acute and chronic stress is associated with the onset and exacerbation of GI symptoms in those without ASD. The present study examined whether GI symptoms in ASD were associated with increases in cortisol, a stress associated endocrine marker, and TNF-alpha and IL-6 in response to stress. As hypothesized, a greater amount of lower GI tract symptoms were significantly associated with post-stress cortisol concentration. The relationship between cortisol response to stress and GI functioning was greater for children who had a history of regressive autism. Exploratory analyses revealed significant correlations between cortisol response, intelligence, and inappropriate speech. In contrast, symptoms of the lower GI tract were not associated with levels of TNF-alpha or IL-6. Significant correlations were found, however, between TNF alpha and IL-6 and irritability, socialization, and intelligence. These findings suggest that individuals with ASD and symptoms of the lower GI tract may have an increased response to stress, but this effect is not associated with concomitant changes in TNF-alpha and IL-6. The relationship between cortisol stress response and lower GI tract symptoms in children with regressive autism, as well as the relationships between cortisol, IL-6, and intelligence in ASD, warrant further investigation. PMID- 27181182 TI - Construct Validity of the Four Square Step Test in Multiple Sclerosis. AB - OBJECTIVE: To expand the construct validity of the Four Square Step Test (FSST) in people with multiple sclerosis (PWMS). DESIGN: Cross-sectional study. SETTING: Multiple sclerosis center. PARTICIPANTS: PWMS (N=218; 133 women, 85 men; mean age, 43.2+/-13.5y; mean disease duration, 7.5+/-7.7y since diagnosis) were enrolled in the study. The Expanded Disability Status Scale score was 3.1+/-1.3, indicating minimal to moderate neurologic disability. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The FSST, posturography measures, 2-minute walk test, timed Up & Go test, timed 25-foot walk, fall status, Falls Efficacy Scale International, Modified Fatigue Impact Scale, instrumented cognitive assessment, and 12-item Multiple Sclerosis Walking Scale. RESULTS: The FSST score of the total sample was 11.0+/-4.9. Significant differences were observed between the very mild, mild, and moderate disability groups: 8.8+/-3.4, 11.1+/-4.9, and 14.1+/-5.3, respectively. In terms of fall status, the fallers demonstrated a significant slower FSST score than the nonfallers (12.5+/-5.7 vs 9.0+/-2.6, respectively). Modest significant correlation scores were found between the FSST and the timed Up & Go test and 2-minute walk test (Pearson rho=.652 and rho= .575, respectively). In terms of posturography, all measures were significantly associated with the FSST scores. A significant positive relation was observed with the visual spatial cognitive domain (Pearson rho=-.207). CONCLUSIONS: The current study supports and broadens the construct validity of the FSST in PWMS. PMID- 27181183 TI - Accelerometer and Global Positioning System Measurement of Recovery of Community Ambulation Across the First 6 Months After Stroke: An Exploratory Prospective Study. AB - OBJECTIVE: To characterize community ambulation and determine if it changes across the first 6 months after discharge from hospital after stroke. DESIGN: Prospective, observational study. SETTING: Community setting. PARTICIPANTS: Subacute stroke survivors with no cognitive impairment or conditions limiting mobility prior to stroke (N=34). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Community ambulation was measured by an accelerometer, Global Positioning System, and activity diary. Measures included the following: volume (step count; time spent in the community, lying/sitting, standing, and walking), frequency (number of community trips; number of and time in short-, medium-, long duration bouts), intensity (number of and time at low-, moderate-, high-intensity bouts), and trip type at 1, 3, and 6 months after hospital discharge. RESULTS: At 1 month participants took on average 1 trip per day in the community, lasting 137+/-113 minutes. Overall, most community ambulation was spread across long duration bouts (>300 steps) lasting 11.3 to 14.1min/d and moderate-intensity bouts (30-80 steps per minute). There was no change in community ambulation trip type (P<.302) or ambulation characteristics over time except for a greater number of and time spent in long ambulation bouts at 6 months only (P<.027). CONCLUSIONS: Total volume and intensity of community ambulation did not change over the first 6 months postdischarge after stroke. However, at 6 months, survivors spent more time in long-duration ambulation bouts. Review of stroke survivors at 6 months after hospital discharge is suggested because this is when changes in community ambulation may first be observed. PMID- 27181184 TI - Transitional object use in adolescence: a developmental phenomenon or a sign of problems? AB - BACKGROUND: Transitional object (TO) use is suggested to be related with various health problems. Prolonged TO use in adolescence is quite common, and research on its associations with health and psychosocial wellbeing is relevant because it does not necessarily represent pathologies in this age group. AIMS: To investigate the role of transitional phenomena and attachment to an inanimate object in adolescence, possible explanatory variables were studied, including sociodemographic and psychosocial factors and self-image. METHODS: The study group consisted of 992 subjects (433 boys and 559 girls), mean age 14.5 years (SD = 0.5), who were studying at comprehensive schools in the City of Turku, Finland. Information about the TO use and background data were collected with a semi structured questionnaire. Mental distress and self-esteem were assessed by the Offer Self-Image Questionnaire (OSIQ). RESULTS: The multivariable logistic regression analysis revealed that, in the whole study group, significant explanatory factors for the TO use included female gender (p < 0.0001), frequent pain and aches (p = 0.008), and, of the OSIQ sub-scales, low Emotional Health (p = 0.006). For girls, significant explanatory factors for the TO use were pain and aches (p = 0.003) and low Emotional Health (p = 0.002). For boys, the only statistically significant explanatory factor was pain and aches (p = 0.02). CONCLUSIONS: The TO may serve as a soothing element for somatoform pain symptoms in adolescence. Identifying of the TO use may help one see an adolescent's possible distress, symptoms of pains, and problems in psychological resilience. PMID- 27181185 TI - A New Suturing Device for Small Arteries. AB - Endoscope-assisted surgery and robot-assisted surgery are not common in cardiac surgery, particularly coronary artery bypass grafting, because of the complex nature of the procedures. We developed a new suturing device that allows for easy performance of such cardiac surgeries in comparison with conventional suturing methods. A total of 63 rabbits were used in this study. The right carotid artery was bypassed using the same side of the jugular vein under endoscopic guidance. Of these, 48 rabbits were operated on using the new devices and 15 rabbits were operated on using conventional polypropylene sutures. The proximal suturing time was 16.6 +/- 5.3 minutes in the group that underwent surgery using the new device (group D) and 22.8 +/- 7.6 minutes in the control group (group C; P < 0.05). The distal suture time was 16.3 +/- 4.2 minutes in group D and 22.8 +/- 6.0 minutes in group C (P < 0.05). The operation time was 113.0 +/- 15.8 minutes in group D and 136.7 +/- 20.6 minutes in group C (P < 0.05). Graft flow was 19.9 +/- 12.8 mL/minute in group D and 12.1 +/- 11.3 mL/minute in group C (P < 0.05). Thus, the operation time and the suture time differed significantly between the groups. This device provides advantages in endoscopic surgery compared to the conventional suture method. PMID- 27181186 TI - Identifying local-scale wilderness for on-ground conservation actions within a global biodiversity hotspot. AB - Protecting wilderness areas (WAs) is a crucial proactive approach to sustain biodiversity. However, studies identifying local-scale WAs for on-ground conservation efforts are still very limited. This paper investigated the spatial patterns of wilderness in a global biodiversity hotspot - Three Parallel Rivers Region (TPRR) in southwest China. Wilderness was classified into levels 1 to 10 based on a cluster analysis of five indicators, namely human population density, naturalness, fragmentation, remoteness, and ruggedness. Only patches characterized by wilderness level 1 and >=1.0 km(2) were considered WAs. The wilderness levels in the northwest were significantly higher than those in the southeast, and clearly increased with the increase in elevation. The WAs covered approximately 25% of TPRR's land, 89.3% of which was located in the >3,000 m elevation zones. WAs consisted of 20 vegetation types, among which temperate conifer forest, cold temperate shrub and alpine ecosystems covered 79.4% of WAs' total area. Most WAs were still not protected yet by existing reserves. Topography and human activities are the primary influencing factors on the spatial patterns of wilderness. We suggest establishing strictly protected reserves for most large WAs, while some sustainable management approaches might be more optimal solutions for many highly fragmented small WAs. PMID- 27181187 TI - Electrocardiographic diagnosis of ST segment elevation myocardial infarction: An evaluation of three automated interpretation algorithms. AB - OBJECTIVE: To assess the validity of three different computerized electrocardiogram (ECG) interpretation algorithms in correctly identifying STEMI patients in the prehospital environment who require emergent cardiac intervention. METHODS: This retrospective study validated three diagnostic algorithms (AG) against the presence of a culprit coronary artery upon cardiac catheterization. Two patient groups were enrolled in this study: those with verified prehospital ST-elevation myocardial infarction (STEMI) activation (cases) and those with a prehospital impression of chest pain due to ACS (controls). RESULTS: There were 500 records analyzed resulting in a case group with 151 patients and a control group with 349 patients. Sensitivities differed between AGs (AG1=0.69 vs AG2=0.68 vs AG3=0.62), with statistical differences in sensitivity found when comparing AG1 to AG3 and AG1 to AG2. Specificities also differed between AGs (AG1=0.89 vs AG2=0.91 vs AG3=0.95), with AG1 and AG2 significantly less specific than AG3. CONCLUSIONS: STEMI diagnostic algorithms vary in regards to their validity in identifying patients with culprit artery lesions. This suggests that systems could apply more sensitive or specific algorithms depending on the needs in their community. PMID- 27181188 TI - Enhanced adsorptive removal of p-nitrophenol from water by aluminum metal-organic framework/reduced graphene oxide composite. AB - In this study, the composite of aluminum metal-organic framework MIL-68(Al) and reduced graphene oxide (MA/RG) was synthesized via a one-step solvothermal method, and their performances for p-nitrophenol (PNP) adsorption from aqueous solution were systematically investigated. The introduction of reduced graphene oxide (RG) into MIL-68(Al) (MA) significantly changes the morphologies of the MA and increases the surface area. The MA/RG-15% prepared at RG-to-MA mass ratio of 15% shows a PNP uptake rate 64% and 123% higher than MIL-68(Al) and reduced graphene oxide (RG), respectively. The hydrogen bond and pi - pi dispersion were considered to be the major driving force for the spontaneous and endothermic adsorption process for PNP removal. The adsorption kinetics, which was controlled by film-diffusion and intra-particle diffusion, was greatly influenced by solution pH, ionic strength, temperature and initial PNP concentration. The adsorption kinetics and isotherms can be well delineated using pseudo-second order and Langmuir equations, respectively. The presence of phenol or isomeric nitrophenols in the solution had minimal influence on PNP adsorption by reusable MA/RG composite. PMID- 27181189 TI - A Novel Transcarotid Approach for Implantation of Balloon-Expandable or Self Expandable Transcatheter Aortic Valves. AB - Transcarotid transcatheter aortic valve replacement (TAVR) is a new alternative in patients with contraindications to other approaches. We report results in 5 patients who underwent TAVR using the common carotid artery approach. Intraprocedural evaluation of the integrity of the circle of Willis was performed by measuring backflow pressure and cerebral oximetry. All patients underwent successful TAVR, without any cerebrovascular or access-related complications. Patient mobilization occurred early postprocedure and 4 of the 5 patients were discharged 3 days after the TAVR procedure. In conclusion, these results suggest that transcarotid access is a safe and feasible secondary TAVR approach. PMID- 27181190 TI - Ataxia-telangiectasia (A-T): An emerging dimension of premature ageing. AB - A-T is a prototype genome instability syndrome and a multifaceted disease. A-T leads to neurodegeneration - primarily cerebellar atrophy, immunodeficiency, oculocutaneous telangiectasia (dilated blood vessels), vestigial thymus and gonads, endocrine abnormalities, cancer predisposition and varying sensitivity to DNA damaging agents, particularly those that induce DNA double-strand breaks. With the recent increase in life expectancy of A-T patients, the premature ageing component of this disease is gaining greater awareness. The complex A-T phenotype reflects the ever growing number of functions assigned to the protein encoded by the responsible gene - the homeostatic protein kinase, ATM. The quest to thoroughly understand the complex A-T phenotype may reveal yet elusive ATM functions. PMID- 27181191 TI - Concurrent Formation of Carbon-Carbon Bonds and Functionalized Graphene by Oxidative Carbon-Hydrogen Coupling Reaction. AB - Oxidative C-H coupling reactions were conducted using graphene oxide (GO) as an oxidant. GO showed high selectivity compared with commonly used oxidants such as (diacetoxyiodo) benzene and 2,3-dichloro-5,6-dicyano-p-benzoquinone. A mechanistic study revealed that radical species contributed to the reaction. After the oxidative coupling reaction, GO was reduced to form a material that shows electron conductivity and high specific capacitance. Therefore, this system could concurrently achieve two important reactions: C-C bond formation via C-H transformation and production of functionalized graphene. PMID- 27181193 TI - A 7-Month-Old Infant with Plantar Garlic Burns. PMID- 27181192 TI - Light-activated photocurrent degradation and self-healing in perovskite solar cells. AB - Solution-processed organometallic perovskite solar cells have emerged as one of the most promising thin-film photovoltaic technology. However, a key challenge is their lack of stability over prolonged solar irradiation. Few studies have investigated the effect of light soaking on hybrid perovskites and have attributed the degradation in the optoelectronic properties to photochemical or field-assisted ion migration. Here we show that the slow photocurrent degradation in thin-film photovoltaic devices is due to the formation of light-activated meta stable deep-level trap states. However, the devices can self-heal completely by resting them in the dark for <1 min or the degradation can be completely prevented by operating the devices at 0 degrees C. We investigate several physical mechanisms to explain the microscopic origin for the formation of these trap states, among which the creation of small polaronic states involving localized cooperative lattice strain and molecular orientations emerges as a credible microscopic mechanism requiring further detailed studies. PMID- 27181194 TI - First or Second Drop of Blood in Capillary Glucose Monitoring: Findings from a Quantitative Study. AB - For clinical nurses, especially those working in emergency departments, it is crucial to measure blood glucose (BG) in an accurate, timely, and safe manner. Many differences in practice exist with regard to use of the first or second drop of blood for testing, and no consistent guidelines are available for capillary BG testing at home or in ED settings. The purpose of this study is to evaluate the BG differences between the first and second drop of capillary blood collected from the same site in patients with type 1 diabetes. METHODS: A consecutive sample of 195 persons with type 1 diabetes who had washed their hands and were not suspected of having hypoglycemia were included in the study. Descriptive and inferential statistical analysis for non-normal distributed variables was performed. RESULTS: A strong correlation emerged between the BG reported in the first and the second drops (Spearman's rho test [rs] 0.979, P < .001; Pearson r 0.978, P < .001). The average BG values obtained from the first and second drops were 184.30 mg/dL (median, 166) and 187.6 mg/dL (median, 172), respectively, and thus the second drop showed higher glucose values compared with the first drop. However, BG values of the second drop were not higher in all occasions: whereas some evaluations reported higher BG values in the second drop capillary sample (n = 123), others reported higher values in the first drop (n = 65), and still others reported identical measurements in the first and second drops (n = 7). Five outliers were present with a BG difference from -39 to -53 mg/dL in the first drop compared with the second drop, and 3 outliers were present with a BG difference from +46 to +57 mg/dL in the first drop compared with the second drop. However, the differences that emerged were not affected by glucose concentration (P = .221). DISCUSSION: Using the first drop of blood in a patient with clean hands allows emergency nurses to perform the test more quickly, resulting in immediate information. Findings indicate that the first drop of blood is adequate for clinical decision making, but the clinician should use judgment if using protocols in which small values (eg, 6 mg/dL) are important, because the first drop is more likely to have a slightly lower value. PMID- 27181195 TI - Engineering 3D bicontinuous hierarchically macro-mesoporous LiFePO4/C nanocomposite for lithium storage with high rate capability and long cycle stability. AB - A highly crystalline three dimensional (3D) bicontinuous hierarchically macro mesoporous LiFePO4/C nanocomposite constructed by nanoparticles in the range of 50~100 nm via a rapid microwave assisted solvothermal process followed by carbon coating have been synthesized as cathode material for high performance lithium ion batteries. The abundant 3D macropores allow better penetration of electrolyte to promote Li(+) diffusion, the mesopores provide more electrochemical reaction sites and the carbon layers outside LiFePO4 nanoparticles increase the electrical conductivity, thus ultimately facilitating reverse reaction of Fe(3+) to Fe(2+) and alleviating electrode polarization. In addition, the particle size in nanoscale can provide short diffusion lengths for the Li(+) intercalation deintercalation. As a result, the 3D macro-mesoporous nanosized LiFePO4/C electrode exhibits excellent rate capability (129.1 mA h/g at 2 C; 110.9 mA h/g at 10 C) and cycling stability (87.2% capacity retention at 2 C after 1000 cycles, 76.3% at 5 C after 500 cycles and 87.8% at 10 C after 500 cycles, respectively), which are much better than many reported LiFePO4/C structures. Our demonstration here offers the opportunity to develop nanoscaled hierarchically porous LiFePO4/C structures for high performance lithium-ion batteries through microwave assisted solvothermal method. PMID- 27181196 TI - Continuous Positive Airway Pressure Improves Quality of Life in Women with Obstructive Sleep Apnea. A Randomized Controlled Trial. AB - RATIONALE: Continuous positive airway pressure (CPAP) is the treatment of choice in patients with symptomatic obstructive sleep apnea (OSA). CPAP treatment improves quality of life (QoL) in men with OSA, but its role in women has not yet been assessed. OBJECTIVES: To investigate the effect of CPAP on QoL in women with moderate to severe OSA. METHODS: We conducted a multicenter, open-label randomized controlled trial in 307 consecutive women diagnosed with moderate to severe OSA (apnea-hypopnea index, >=15) in 19 Spanish sleep units. Women were randomized to receive effective CPAP therapy (n = 151) or conservative treatment (n = 156) for 3 months. The primary endpoint was the change in QoL based on the Quebec Sleep Questionnaire. Secondary endpoints included changes in daytime sleepiness, mood state, anxiety, and depression. Data were analyzed on an intention-to-treat basis with adjustment for baseline values and other relevant clinical variables. MEASUREMENTS AND MAIN RESULTS: The women in the study had a mean (SD) age of 57.1 (10.1) years and a mean (SD) Epworth Sleepiness Scale score of 9.8 (4.4), and 77.5% were postmenopausal. Compared with the control group, the CPAP group achieved a significantly greater improvement in all QoL domains of the Quebec Sleep Questionnaire (adjusted treatment effect between 0.53 and 1.33; P < 0.001 for all domains), daytime sleepiness (-2.92; P < 0.001), mood state (-4.24; P = 0.012), anxiety (-0.89; P = 0.014), depression (-0.85; P = 0.016), and the physical component summary of the 12-item Short Form Health Survey (2.78; P = 0.003). CONCLUSIONS: In women with moderate or severe OSA, 3 months of CPAP therapy improved QoL, mood state, anxiety and depressive symptoms, and daytime sleepiness compared with conservative treatment. Clinical trial registered with www.clinicaltrials.gov (NCT02047071). PMID- 27181198 TI - Molecular Mechanism of HIV-1 Vpr for Binding to Importin-alpha. AB - Viral protein R (Vpr) is an accessory gene product of human immunodeficiency virus type 1 (HIV-1) that plays multiple important roles associated with viral replication. Structural studies using NMR have revealed that Vpr consists of three alpha-helices and contains flexible N- and C-termini. However, the molecular mechanisms associated with Vpr function have not been elucidated. To investigate Vpr multifunctionality, we performed an X-ray crystallographic study of Vpr complexes containing importin-alpha, a known Vpr binding partner present in host cells. Elucidation of the crystal structure revealed that the flexible C terminus changes its conformation to a twisted beta-turn via an induced-fit mechanism, enabling binding to a minor nuclear localization signal (NLS) site of importin-alpha. The Vpr C-terminus can also bind with major NLS sites of importin alpha in an extended conformation in different ways. These results, which represent the first reported crystallographic analysis of Vpr, demonstrate the multifunctional aspects that enable Vpr interaction with a variety of cellular proteins. PMID- 27181200 TI - A moveable feast: Contemporary relational food cultures emerging from local food networks. AB - Although the globalised food system delivers unparalleled food variety and quantity to most in the developed world it also disconnects consumers from where, how and by whom food is grown. This change in the food system has resulted in an acceptance of an anonymous and homogeneous food supply, which has contributed to over-consumption and the rise in diet-related diseases. 'Nutritionism' responds to this issue by maintaining that a 'healthy diet' can be achieved by consuming the correct balance of energy and nutrients, but with limited success. Yet, some food cultures can moderate the effects of the environmental drivers of increasing global obesity rates. This paper draws on this premise and presents an alternative eco-dietetic response, exploring people's meaning-making of food and food culture through local food networks. This research used narrative inquiry methodology and purposive sampling to gather stories through focus group conversations. Twenty people attended focus groups comprised of food procurers from one of three local food networks in the Canberra region: community gardens, a modified Community Supported Agriculture (CSA) and farmers' markets. The findings showed that those using local food networks enjoyed a 'contemporary relational food culture' that highlighted the importance of people, place and time, in their visceral experiences of food. The community gardeners made meaning of food through their connections to the earth and to others. The farmers' market and CSA food procurers valued the seasonal, local and ethical food produced by their beloved farmer(s). This paper provides qualitative evidence that local food networks enable people to enjoy multi-dimensional relationships to food. Further research is required to examine whether experiencing a contemporary relational food culture can lead to improved health outcomes for people and the planet. PMID- 27181197 TI - Interferon-Inducible GTPases in Host Resistance, Inflammation and Disease. AB - Cell-autonomous immunity is essential for host organisms to defend themselves against invasive microbes. In vertebrates, both the adaptive and the innate branches of the immune system operate cell-autonomous defenses as key effector mechanisms that are induced by pro-inflammatory interferons (IFNs). IFNs can activate cell-intrinsic host defenses in virtually any cell type ranging from professional phagocytes to mucosal epithelial cells. Much of this IFN-induced host resistance program is dependent on four families of IFN-inducible GTPases: the myxovirus resistance proteins, the immunity-related GTPases, the guanylate binding proteins (GBPs), and the very large IFN-inducible GTPases. These GTPase families provide host resistance to a variety of viral, bacterial, and protozoan pathogens through the sequestration of microbial proteins, manipulation of vesicle trafficking, regulation of antimicrobial autophagy (xenophagy), execution of intracellular membranolytic pathways, and the activation of inflammasomes. This review discusses our current knowledge of the molecular function of IFN inducible GTPases in providing host resistance, as well as their role in the pathogenesis of autoinflammatory Crohn's disease. While substantial advances were made in the recent past, few of the known functions of IFN-inducible GTPases have been explored in any depth, and new functions await discovery. This review will therefore highlight key areas of future exploration that promise to advance our understanding of the role of IFN-inducible GTPases in human diseases. PMID- 27181199 TI - Glycemic control and adherence to basal insulin therapy in Taiwanese patients with type 2 diabetes mellitus. AB - AIMS/INTRODUCTION: The aim of the present study was to assess the glycemic control, adherence and treatment satisfaction in a real-world setting with basal insulin therapy in type 2 diabetes patients in Taiwan. MATERIALS AND METHODS: This was a multicenter, prospective, observational registry. A total of 836 patients with type 2 diabetes taking oral antidiabetic drugs with glycated hemoglobin (HbA1c) >7% entered the study. Basal insulin was given for 24 weeks. All treatment choices and medical instructions were at the physician's discretion to reflect real-life practice. RESULTS: After 24-week treatment, 11.7% of patients reached set HbA1c goals without severe hypoglycemia (primary effectiveness end-point). HbA1c and fasting blood glucose were significantly decreased from (mean +/- SD) 10.1 +/- 1.9% to 8.7 +/- 1.7% (-1.4 +/- 2.1%, P < 0.0001) and from 230.6 +/- 68.8 mg/dL to 159.1 +/- 55.6 mg/dL (-67.4 +/- 72.3 mg/dL, P < 0.0001), respectively. Patients received insulin therapy at a frequency of nearly one shot per day on average, whereas self-monitoring of blood glucose was carried out approximately four times a week. Hypoglycemia was reported by 11.4% of patients, and only 0.7% of patients experienced severe hypoglycemia. Slight changes in weight (0.7 +/- 2.4 kg) and a low incidence of adverse drug reactions (0.4%) were also noted. The score of 7-point treatment satisfaction rated by patients was significantly improved by 1.9 +/- 1.7 (P < 0.0001). CONCLUSIONS: Basal insulin therapy was associated with a decrease in HbA1c and fasting blood glucose, and an improved treatment satisfaction. Most patients complied with physicians' instructions. The treatment was generally well tolerated by patients with type 2 diabetes, but findings pointed out the need to reinforce the early and appropriate uptitration to achieve treatment targets. PMID- 27181201 TI - Dietary interventions among university students: A systematic review. AB - PURPOSE: This study aimed to provide an overview of available literature on interventions aiming to improve dietary intake among university students. MATERIALS AND METHODS: A systematic review was conducted following the PRISMA guidelines. Web of Science, PubMed, PsycINFO and SPORTDiscus were searched for relevant articles. Risk of bias was assessed using the Academy of Nutrition and Dietetics Quality Criteria Checklist for Primary Research. RESULTS: Twenty studies were identified, consisting of 12 randomised controlled trials, 1 quasi experiment and 7 pre-experiments. Six studies were conducted outside the US. Risk of bias assessment revealed an average quality score of 5.8/10. Of the 13 interventions which were effective in improving students' dietary intake, 8 used an intrapersonal approach, with 6 of them using the web or some kind of media to facilitate the intervention. The 5 remaining studies used an environmental (point of-purchase) approach. Only 1 intervention, using 10 web-based lessons, based on non-diet principles and focused on eating competence and size acceptance to promote healthy eating, was found to be effective in the long term. CONCLUSIONS: Nutrition education, enhancing self-regulation components towards dietary intake (often facilitated by the worldwide web or other media devices), and point-of purchase messaging strategies may improve university or college students' dietary intake. Future high quality randomised controlled trials should evaluate sustainability of intervention effects, as well as further investigate the effectiveness of realistic and low-cost environmental (preferably combined with intrapersonal) interventions which can easily and instantly reach a great part of the university population. PMID- 27181203 TI - p27T187A knockin identifies Skp2/Cks1 pocket inhibitors for advanced prostate cancer. AB - SCFSkp2/Cks1 ubiquitinates Thr187-phosphorylated p27 for degradation. Overexpression of Skp2 coupled with underexpression of p27 are frequent characteristics of cancer cells. When the role of SCFSkp2/Cks1-mediated p27 ubiquitination in cancer was specifically tested by p27 Thr187-to-Ala knockin (p27T187A KI), it was found dispensable for KrasG12D-induced lung tumorigenesis but essential for Rb1-deficient pituitary tumorigenesis. Here we identify pRb and p53 doubly deficient (DKO) prostate tumorigenesis as a context in which p27 ubiquitination by SCFSkp2/Cks1 is required for p27 downregulation. p27 protein accumulated in prostate when p27T187A KI mice underwent DKO prostate tumorigenesis. p27T187A KI or Skp2 knockdown (KD) induced similar degrees of p27 protein accumulation in DKO prostate cells, and Skp2 KD did not further increase p27 protein in DKO prostate cells that contained p27T187A KI (AADKO prostate cells). p27T187A KI activated an E2F1-p73-apoptosis axis in DKO prostate tumorigenesis, slowed disease progression and significantly extended survival. Querying co-occurrence relationships among RB1, TP53, PTEN, NKX3-1 and MYC in TCGA of prostate cancer identified co-inactivation of RB1 and TP53 as the only statistically significant co-occurrences in metastatic castration-resistant prostate cancer (mCRPC). Together, our study identifies Skp2/Cks1 pocket inhibitors as potential therapeutics for mCRPC. Procedures for establishing mCRPC organoid cultures from contemporary patients were recently established. An Skp2/Cks1 pocket inhibitor preferentially collapsed DKO prostate tumor organoids over AADKO organoids, which spontaneously disintegrated over time when DKO prostate tumor organoids grew larger, setting the stage to translate mouse model findings to precision medicine in the clinic on the organoid platform. PMID- 27181202 TI - SUMOylation and SENP3 regulate STAT3 activation in head and neck cancer. AB - Hyperphosphorylation of signal transducer and activator of transcription 3 (STAT3) has been found in various types of human cancers, including head and neck cancer (HNC). Although smoking is critical in the development and progression of HNC, how tobacco components activate STAT3 is unclear. We demonstrated that exposure of HNC cell lines to a tobacco extract induced a rapid Y705 phosphorylation of STAT3 and a rapid increase in the SUMO protease SENP3 that depended on a simultaneous increase in reactive oxygen species. We identified that SUMOylation at the lysine 451 site facilitated STAT3 binding to the phosphatase TC45 through an SUMO-interacting motif of TC45. SENP3 could thus enhance STAT3 phosphorylation by de-conjugating the SUMO2/3 modification of STAT3. Knocking-down of SENP3 greatly impaired basal and induced STAT3 phosphorylation by tobacco extract or interleukin 6. A correlation between SENP3 protein levels and STAT3 Y705 phosphorylation levels in human laryngeal carcinoma specimens was found, which was more significant in the specimens derived from the smoker patients and with poor clinicopathological parameters. Our data identified SUMOylation as a previously undescribed post-translational modification of STAT3 and SENP3 as a critical positive modulator of tobacco- or cytokine-induced STAT3 activation. These findings provide novel insights into the hyperphosphorylation of STAT3 in development of HNC. PMID- 27181204 TI - The C/EBPdelta protein is stabilized by estrogen receptor alpha activity, inhibits SNAI2 expression and associates with good prognosis in breast cancer. AB - Hypoxia and inflammatory cytokines like interleukin-6 (IL-6, IL6) are strongly linked to cancer progression, and signal in part through the transcription factor Ccaat/enhancer-binding protein delta (C/EBPdelta, CEBPD), which has been shown to promote mesenchymal features and malignant progression of glioblastoma. Here we report a different role for C/EBPdelta in breast cancer. We found that the C/EBPdelta protein is expressed in normal breast epithelial cells and in low grade cancers. C/EBPdelta protein (but not mRNA) expression correlates with estrogen receptor (ER+) and progesterone receptor (PGR) expression and longer progression-free survival of breast cancer patients. Specifically in ER+ breast cancers, CEBPD-but not the related CEBPB-mRNA in combination with IL6 correlated with lower risk of progression. Functional studies in cell lines showed that ERalpha promotes C/EBPdelta expression at the level of protein stability by inhibition of the FBXW7 pathway. Furthermore, we found that C/EBPdelta attenuates cell growth, motility and invasiveness by inhibiting expression of the SNAI2 (Slug) transcriptional repressor, which leads to expression of the cyclin dependent kinase inhibitor CDKN1A (p21CIP1/WAF1). These findings identify a molecular mechanism by which ERalpha signaling reduces the aggressiveness of cancer cells, and demonstrate that C/EBPdelta can have different functions in different types of cancer. Furthermore, our results support a potentially beneficial role for the IL-6 pathway specifically in ER+ breast cancer and call for further evaluation of the role of intra-tumoral IL-6 expression and of which cancers might benefit from current attempts to target the IL-6 pathway as a therapeutic strategy. PMID- 27181205 TI - Overexpression of maelstrom promotes bladder urothelial carcinoma cell aggressiveness by epigenetically downregulating MTSS1 through DNMT3B. AB - We have recently identified and characterized a novel oncogene, maelstrom (MAEL) from 1q24, in the pathogenesis of hepatocellular carcinoma. In this study, MAEL was investigated for its oncogenic role in urothelial carcinoma of the bladder (UCB) tumorigenesis/aggressiveness and underlying molecular mechanisms. Here, we report that overexpression of MAEL in UCB is important in the acquisition of an aggressive and/or poor prognostic phenotype. In UCB cell lines, knockdown of MAEL by short hairpin RNA is sufficient to inhibit cell growth, invasiveness/metastasis and suppressed epithelial-mesenchymal transition (EMT), whereas ectopic overexpression of MAEL promoted cell growth, invasive and/or metastatic capacity and enhanced EMT both in vitro and in vivo. We further demonstrate that MAEL could induce UCB cell EMT by downregulating a critical downstream target, the metastasis suppressor 1 (MTSS1) gene, ultimately leading to an increased invasiveness of cancer cells. Notably, overexpression of MAEL in UCB cells substantially enhanced the enrichment of DNA methyltrans-ferase (DNMT)3B and histone deacetylase (HDAC)1/2 on the promoter of the MTSS1, and thereby epigenetically suppressing the MTSS1 transcription. Downregulation of MTSS1 by MAEL in UCB cells is partially dependent on DNMT3B. Furthermore, we identify that beside the gene amplification of MAEL, miR-186 is a key negative regulator of MAEL and downregulation of miR-186 is another important mechanism for MAEL overexpression in UCBs. These data suggest that overexpression of MAEL, caused by gene amplification and/or decreased miR-186, has a critical oncogenic role in UCB pathogenesis by downregulation of MTSS1, and MAEL could be used as a novel prognostic marker and/or effective therapeutic target for human UCB. PMID- 27181206 TI - RAC1 GTPase promotes the survival of breast cancer cells in response to hyper fractionated radiation treatment. AB - Radiation therapy is a staple approach for cancer treatment, whereas radioresistance of cancer cells remains a substantial clinical problem. In response to ionizing radiation (IR) induced DNA damage, cancer cells can sustain/activate pro-survival signaling pathways, leading to apoptotic resistance and induction of cell cycle checkpoint/DNA repair. Previous studies show that Rac1 GTPase is overexpressed/hyperactivated in breast cancer cells and is associated with poor prognosis. Studies from our laboratory reveal that Rac1 activity is necessary for G2/M checkpoint activation and cell survival in response to IR exposure of breast and pancreatic cancer cells. In this study, we investigated the effect of Rac1 on the survival of breast cancer cells treated with hyper-fractionated radiation (HFR), which is used clinically for cancer treatment. Results in this report indicate that Rac1 protein expression is increased in the breast cancer cells that survived HFR compared with parental cells. Furthermore, this increase of Rac1 is associated with enhanced activities of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and nuclear factor kappaB (NF-kappaB) signaling pathways and increased levels of anti-apoptotic protein Bcl-xL and Mcl-1, which are downstream targets of ERK1/2 and NF-kappaB signaling pathways. Using Rac1-specific inhibitor and dominant-negative mutant N17Rac1, here we demonstrate that Rac1 inhibition decreases the phosphorylation of ERK1/2 and inhibitory kappaBalpha (IkappaBalpha), as well as the levels of Bcl xL and Mcl-1 protein in the HFR-selected breast cancer cells. Moreover, inhibition of Rac1 using either small molecule inhibitor or dominant-negative N17Rac1 abrogates clonogenic survival of HFR-selected breast cancer cells and decreases the level of intact poly(ADP-ribose) polymerase, which is indicative of apoptosis induction. Collectively, results in this report suggest that Rac1 signaling is essential for the survival of breast cancer cells subjected to HFR and implicate Rac1 in radioresistance of breast cancer cells. These studies also provide the basis to explore Rac1 as a therapeutic target for radioresistant breast cancer cells. PMID- 27181207 TI - A CCL8 gradient drives breast cancer cell dissemination. AB - The migration of cancer cells towards gradients of chemoattractive factors represents a potential, yet elusive, mechanism that may contribute to cancer cell dissemination. Here we provide evidence for the maintenance of a gradient of increasing CCL8 concentration between the epithelium, the stroma and the periphery that is instrumental for breast cancer cells' dissemination. In response to signals elicited by the neoplastic epithelium, CCL8 production is enhanced in stromal fibroblasts at the tumor margins and in tissues at which breast cancer cells tend to metastasize such as the lungs and the brain. Manipulation of CCL8 activity influences the histology of the tumors and promotes major steps of the metastatic process such as invasion to adjacent stroma, intravasation and ultimately extravasation and seeding. These findings exemplify how gradients of chemoattractive factors such as CCL8, drive metastasis and suggest that interference with their operation may provide means for breast cancer management. PMID- 27181208 TI - eEF-2 kinase is a critical regulator of Warburg effect through controlling PP2A-A synthesis. AB - Cancer cells predominantly metabolize glucose by glycolysis to produce energy in order to meet their metabolic requirement, a phenomenon known as Warburg effect. Although Warburg effect is considered a peculiarity critical for survival and proliferation of cancer cells, the regulatory mechanisms behind this phenomenon remain incompletely understood. We report here that eukaryotic elongation factor 2 kinase (eEF-2K), a negative regulator of protein synthesis, has a critical role in promoting glycolysis in cancer cells. We showed that deficiency in eEF-2K significantly reduced the uptake of glucose and decreased the productions of lactate and adenosine triphosphate in tumor cells and in the Ras-transformed mouse embryonic fibroblasts. We further demonstrated that the promotive effect of eEF-2K on glycolysis resulted from the kinase-mediated restriction of synthesis of the protein phosphatase 2A-A (PP2A-A), a key factor that facilitates the ubiquitin-proteasomal degradation of c-Myc protein, as knockdown of eEF-2K expression led to a significant increase in PP2A-A protein synthesis and remarkable downregulation of c-Myc and pyruvate kinase M2 isoform, the key glycolytic enzyme transcriptionally activated by c-Myc. In addition, depletion of eEF-2K reduced the ability of the transformed cells to proliferate and enhanced the sensitivity of tumor cells to chemotherapy both in vitro and in vivo. These results, which uncover a role of the eEF-2K-mediated control of PP2A-A in tumor cell glycolysis, provide new insights into the regulation of the Warburg effect. PMID- 27181210 TI - Pteropod eggs released at high pCO2 lack resilience to ocean acidification. AB - The effects of ocean acidification (OA) on the early recruitment of pteropods in the Scotia Sea, was investigated considering the process of spawning, quality of the spawned eggs and their capacity to develop. Maternal OA stress was induced on female pteropods (Limacina helicina antarctica) through exposure to present day pCO2 conditions and two potential future OA states (750 MUatm and 1200 MUatm). The eggs spawned from these females, both before and during their exposure to OA, were incubated themselves in this same range of conditions (embryonic OA stress). Maternal OA stress resulted in eggs with lower carbon content, while embryonic OA stress retarded development. The combination of maternal and embryonic OA stress reduced the percentage of eggs successfully reaching organogenesis by 80%. We propose that OA stress not only affects the somatic tissue of pteropods but also the functioning of their gonads. Corresponding in-situ sampling found that post larval L. helicina antarctica concentrated around 600 m depth, which is deeper than previously assumed. A deeper distribution makes their exposure to waters undersaturated for aragonite more likely in the near future given that these waters are predicted to shoal from depth over the coming decades. PMID- 27181211 TI - An analogue of atrial natriuretic peptide (C-ANP4-23) modulates glucose metabolism in human differentiated adipocytes. AB - The present study was undertaken to investigate the effects of C-atrial natriuretic peptide (C-ANP4-23) in human adipose-derived stem cells differentiated into adipocytes over 10 days (1 MUM for 4 h). The intracellular cAMP, cGMP and protein kinase A levels were determined by ELISA and gene and protein expression were determined by qRT-PCR and Western blot, respectively, in the presence or absence of C-ANP4-23. The levels of lipolysis and glucose uptake were also determined. C-ANP4-23 treatment significantly increased the intracellular cAMP levels and the gene expression of glucose transporter type 4 (GLUT4) and protein kinase, AMP-activated, alpha 1 catalytic subunit (AMPK). Western blot showed a significant increase in GLUT4 and phosphor-AMPKalpha levels. Importantly, the adenylate cyclase inhibitor SQ22536 abolished these effects. Additionally, C-ANP4-23 increased glucose uptake by 2-fold. Our results show that C-ANP4-23 enhances glucose metabolism and might contribute to the development of new peptide-based therapies for metabolic diseases. PMID- 27181212 TI - Successful disabling of the 5' UTR of HCV using adeno-associated viral vectors to deliver modular multimeric primary microRNA mimics. AB - Chronic hepatitis C virus (HCV) infection is a major health concern and is strongly associated with cirrhosis, hepatocellular carcinoma and liver-related mortality. The HCV genome is the template for both protein translation and viral replication and, being RNA, is amenable to direct genetic silencing by RNA interference (RNAi). HCV is a highly mutable virus and is capable of escaping RNAi-mediated silencing. This has highlighted the importance of developing RNAi based therapy that simultaneously targets multiple regions of the HCV genome. To develop a multi-targeting RNAi activator, a novel approach for the generation of anti-HCV gene therapy was investigated. Five artificial primary miRNA (pri-miR) were each designed to mimic the naturally occurring monomeric pri-miR-31. Potent knockdown of an HCV reporter was seen with four of the five constructs and were processed according to the intended design. The design of the individual pri-miR mimics enabled the modular assembly into multimeric mimics of any possible conformation. Consequently the four potent pri-miR mimics were used to generate polycistronic cassettes, which showed impressive silencing of an HCV target. To further their application as a gene therapy, recombinant adeno-associated viral (rAAV) vectors that express the polycistronic pri-miR mimics were generated. All AAV-delivered anti-HCV pri-miR mimics significantly knocked down the expression of an HCV target and showed inhibition of HCV replicon replication. Here we describe a protocol for the generation of therapeutic rAAVs that express modular polycistronic pri-miR cassettes allowing for rapid alteration and generation of tailored therapeutic constructs against HCV. PMID- 27181209 TI - Microphthalmia-associated transcription factor suppresses invasion by reducing intracellular GTP pools. AB - Melanoma progression is associated with increased invasion and, often, decreased levels of microphthalmia-associated transcription factor (MITF). Accordingly, downregulation of MITF induces invasion in melanoma cells; however, little is known about the underlying mechanisms. Here, we report for the first time that depletion of MITF results in elevation of intracellular GTP levels and increased amounts of active (GTP-bound) RAC1, RHO-A and RHO-C. Concomitantly, MITF-depleted cells display larger number of invadopodia and increased invasion. We further demonstrate that the gene for guanosine monophosphate reductase (GMPR) is a direct MITF target, and that the partial repression of GMPR accounts mostly for the above phenotypes in MITF-depleted cells. Reciprocally, transactivation of GMPR is required for MITF-dependent suppression of melanoma cell invasion, tumorigenicity and lung colonization. Moreover, loss of GMPR accompanies downregulation of MITF in vemurafenib-resistant BRAFV600E-melanoma cells and underlies the increased invasion in these cells. Our data uncover novel mechanisms linking MITF-dependent inhibition of invasion to suppression of guanylate metabolism. PMID- 27181213 TI - Development of RT-qPCR assays for the specific identification of two major genotypes of avian infectious bronchitis virus. AB - Infectious bronchitis virus (Gammacoronavirus, Coronaviridae) is a genetically variable RNA virus (27.6kb) that causes one of the most persistent respiratory disease in poultry. The virus is classified in genotypes with different epidemiological relevance and clinical implications. The present study reports the development and validation of specific RT-qPCR assays for the detection of two major IBV genotypes: South America I (SAI) and Asia/South America II (A/SAII). The SAI genotype is an exclusive and widespread South American lineage while the A/SAII genotype is distributed in Asia, Europe and South America. Both identification assays employ TaqMan probes that hybridize with unique sequences in the spike glycoprotein gene. The assays successfully detected all the assessed strains belonging to both genotypes, showing high specificity and absence of cross-reactivity. Using serial dilutions of in vitro-transcribed RNA we obtained acceptable determination coefficients, PCR efficiencies and relatively small intra- and inter-assay variability. The assays demonstrated a wide dynamic range between 10(1)-10(7) and 10(2)-10(7) RNA copies/reaction for SAI and A/SAII strains, respectively. The possibility to characterize a large number of samples in a rapid, sensitive and reproducible way makes these techniques suitable tools for routine testing, IBV control, and epidemiological research in poultry. PMID- 27181214 TI - HLA-A*33-DR3 and A*33-DR9 haplotypes enhance the risk of type 1 diabetes in Han Chinese. AB - AIMS/INTRODUCTION: To investigate the typing for human leukocyte antigen (HLA) class I in Chinese patients with type 1 diabetes as a complement screening for HLA class II. MATERIALS AND METHODS: A total of 212 type 1 diabetic patients and 200 healthy controls were enrolled. The genetic polymorphisms of HLA class I and II were examined with a high-resolution polymerase chain reaction sequence-based typing method. RESULTS: The haplotype, A*33:03-B*58:01-C*03:02(A33), was associated with type 1 diabetes (P = 1.0 * 10(-4) , odds ratio 3.2 [1.738 5.843]). The A33-DR3 and A33-DR9 haplotypes significantly enhanced the risk of type 1 diabetes (A33-DR3, odds ratio 5.1 [2.40-10.78], P = 4.0 * 10(-6) ; A33 DR9, odds ratio 13.0 [1.69-100.32], P = 0.004). In type 1 diabetic patients, compared with A33-DR3-negative carriers, A33-DR3-positive carriers had significantly lower percentages of CD3(+) CD4(+) T cells (42.5 +/- 7.72 vs 37.0 +/- 8.35%, P = 0.023), higher percentages of CD3(+) CD8(+) T cells (27.4 +/- 7.09 vs 32.8 +/- 5.98%, P = 0.005) and T-cell receptor alpha/beta T cells (70.0 +/- 7.00 vs 73.6 +/- 6.25%, P = 0.031), and lower CD4/CD8 ratios (1.71 +/- 0.75 vs 1.16 +/- 0.35, P = 0.003). CONCLUSIONS: It is the first time that the haplotypes A33-DR3 and A33-DR9 were found with an enhanced predisposition to type 1 diabetes in Han Chinese. A33-DR3 was associated with a reduction in the helper-to cytotoxic cell ratio and preferential increase of T-cell receptor alpha/beta T cell. The typing for HLA class I and its immunogenetic effects are important for more accurate HLA class II haplotype risk prediction and etiology research in type 1 diabetic patients. PMID- 27181216 TI - [Lymphoproliferative pulmonary infiltration: A diagnosis to keep in mind in pulmonary infiltrates in patient with chronic lymphocytic leukemia]. PMID- 27181215 TI - Polycomb repressive complex 1 controls uterine decidualization. AB - Uterine stromal cell decidualization is an essential part of the reproductive process. Decidual tissue development requires a highly regulated control of the extracellular tissue remodeling; however the mechanism of this regulation remains unknown. Through systematic expression studies, we detected that Cbx4/2, Rybp, and Ring1B [components of polycomb repressive complex 1 (PRC1)] are predominantly utilized in antimesometrial decidualization with polyploidy. Immunofluorescence analyses revealed that PRC1 members are co-localized with its functional histone modifier H2AK119ub1 (mono ubiquitination of histone-H2A at lysine-119) in polyploid cell. A potent small-molecule inhibitor of Ring1A/B E3-ubiquitin ligase or siRNA-mediated suppression of Cbx4 caused inhibition of H2AK119ub1, in conjunction with perturbation of decidualization and polyploidy development, suggesting a role for Cbx4/Ring1B-containing PRC1 in these processes. Analyses of genetic signatures by RNA-seq studies showed that the inhibition of PRC1 function affects 238 genes (154 up and 84 down) during decidualization. Functional enrichment analyses identified that about 38% genes primarily involved in extracellular processes are specifically targeted by PRC1. Furthermore, ~15% of upregulated genes exhibited a significant overlap with the upregulated Bmp2 null induced genes in mice. Overall, Cbx4/Ring1B-containing PRC1 controls decidualization via regulation of extracellular gene remodeling functions and sheds new insights into underlying molecular mechanism(s) through transcriptional repression regulation. PMID- 27181221 TI - The critical care nurse work environment, physician staffing, and risk for ventilator-associated pneumonia. AB - We examined the relationship between intensivist physician staffing, nurse work environment, and ventilator-associated pneumonia (VAP) in 25 intensive care units. We found a significant interaction between the nurse work environment, intensivist physician staffing, and VAP. Future work may need to focus on fostering organizational collaboration between nursing and medicine to leverage skills of both clinician groups to reduce risk for VAP in critically ill patients. PMID- 27181222 TI - Are health care personnel trained in correct use of personal protective equipment? AB - Effective use of personal protective equipment (PPE) is essential to protect personnel and patients in health care settings. However, in a survey of 222 health care personnel, PPE training was often suboptimal with no requirement for demonstration of proficiency. Fourteen percent of physicians reported no previous training in use of PPE. PMID- 27181217 TI - Study on autonomic dysfunction and metabolic syndrome in Chinese patients. AB - AIMS/INTRODUCTION: There is still a lack of simple methods and instruments for the early assessment of autonomic dysfunction in metabolic syndrome patients. Assessment of sudomotor function has been proposed to explore autonomic function, and could be used as an early biomarker for metabolic syndrome. In the present study, we use a quick and non-invasive method to measure sudomotor function, and aimed to evaluate its efficacy to identify metabolic syndrome in a Chinese population. MATERIALS AND METHODS: Information on the 1,160 Chinese participants involved in the study, such as age, sex, blood pressure, waist circumference, body mass index, fasting plasma glucose and lipid profile, and SUDOSCAN, was recorded. During the sudomotor test, patients were asked to place their bare hands and feet on large electrodes. The test took 2 min to carry out, was painless and no participant preparation was required. RESULTS: A total of 567 participants were diagnosed with metabolic syndrome. The prevalence of metabolic syndrome correlated significantly with increasing SUDOSCAN cardiac risk score (P for trend <0.0001). Furthermore, an increase in cardiac risk score value was associated with an increase in the number of metabolic syndrome components (P for trend <0.0001). Compared with the no-risk group (cardiac risk score <20), participants in the high-risk group (cardiac risk score >=30) had a 2.83-fold increased risk of prevalent metabolic syndrome (P < 0.0001), and 1.51-fold increased risk (P = 0.01) after adjustments. CONCLUSIONS: Autonomic dysfunction is correlated to components of metabolic syndrome. The role of SUDOSCAN in the screening of at-risk populations for metabolic syndrome has to be confirmed by further studies. PMID- 27181223 TI - High frequency tympanometry (1000Hz) in young infants and its comparison with otoacoustic emissions, otomicroscopy and 226Hz tympanometry. AB - INTRODUCTION AND OBJECTIVE: In the first 6 months of life, 226Hz tympanometry is considered an ineffective procedure for the diagnosis of otitis media with effusion. With the introduction of universal hearing screening, the use of high frequency 1000Hz (1kHz) tympanometry has been recommended. To optimise the diagnosis of neonatal hearing loss, we present this comparison, from the clinical point of view, of the results of 226Hz and 1kHz tympanometry in infants. MATERIALS AND METHODS: We designed a prospective study of 100 children under 9 months of age proceeding from our hearing screening program. We compare the result of tympanometry with binocular microscopy and transient evoked otoacoustic emissions. RESULTS: The application of transient otoacoustic emissions, otomicroscopy and 226Hz and 1kHz tympanometry has shown its usefulness in the management of otitis media with effusion of young infants, with a similar effectiveness between the 4 tests. CONCLUSION: The joint use of otomicroscopy, transient otoacoustic emissions and 226Hz and 1kHz tympanometry, has allowed us to diagnose otitis media with effusion in young infants more accurately than each test separately. We recommend initial use of 1kHz tympanometry, at least in children younger than 7 months, but in the presence of hearing loss or an unclear result, 226Hz tympanometry is a good diagnostic complement. PMID- 27181224 TI - Ultrasonographical assessment of implanted biodegradable device for long-term slow release of methotrexate into the vitreous. AB - Our group has developed a biodegradable drug delivery device (micro-implant) for long-term slow intraocular release of methotrexate (MTX) that can be implanted in the peripheral vitreous. The purpose of this study was to assess the position of the implanted devices and the status of the adjacent vitreous and peripheral retina over time using B-scan ocular ultrasonography (US). In each of the eight New Zealand rabbits used in this study, a chitosan (CS) and poly-lactic acid (PLA)-based micro-implant containing approximately 400 MUg of MTX and a placebo micro-implant without MTX were inserted into the peripheral vitreous of the right and left eyes, respective, employing minimally invasive surgery. B-scan US imaging was performed on all of the rabbits immediately after implant insertion and on two rabbits at each of several pre-determined time points post-insertion (post-insertion days 5, 12, 19, and 33) to evaluate the position of the micro implants and identify any evident morphological changes in the micro-implants and in the peripheral retina and vitreous during treatment. US imaging revealed stable positioning of the PLA-coated CS-based MTX micro-implant and the placebo micro-implant in the respective eyes throughout the study and lack of any changes in size, shape or sonoreflectivity of the micro-implants or abnormalities of the peripheral vitreous or retina in any of the study eyes. In summary, US did not show any evident morphological changes in the micro-implants, shifts in post insertion position of the micro-implants, or identifiable changes in the micro implants or peripheral vitreous and retina of the study eyes. PMID- 27181225 TI - Amyloid beta deposition and phosphorylated tau accumulation are key features in aged choroidal vessels in the complement factor H knock out model of retinal degeneration. AB - Extra-cellular deposition including amyloid beta (Abeta) is a feature of retinal ageing. It has been documented for Bruch's membrane (BM) where Abeta is elevated in complement factor H knockout mice (Cfh(-/-)) proposed as a model for age related macular degeneration. However, arterial deposition in choroidal vessels prior to perfusion across BM has not been examined. Abeta is associated with tau phosphorylation and these are linked in blood vessels in Alzheimers Disease where they can drive perivascular pathology. Here we ask if Abeta, tau and phosphorylated tau are features of ageing in choroidal vessels in 12 month C57 BL/6 and Cfh(-/-) mice, using immune staining and Western blot analysis. Greater levels of Abeta and phosphorylated tau are found in choroidal vessels in Cfh(-/-) mice. Western blot revealed a 40% increase in Abeta in Cfh(-/-) over C57 BL/6 mice. Abeta deposits coat around 55% of the luminal wall in Cfh(-/-) compared to only about 40% in C57 BL/6. Total tau was similar in both groups, but phosphorylated tau increased by >100% in Cfh(-/-) compared to C57 BL/6 and covered >75% of the luminal wall compared to 50% in C57 BL/6. Hence, phosphorylated tau is a marked choroidal feature in this mouse model. Abeta deposition was clumped in Cfh(-/-) mice and likely to influence blood flow dynamics. Disturbed flow is associated with atherogenesis and may be related to the accumulation of membrane attack complex recently identified between choroidal vessels in those at high risk of macular degeneration due to complement factor H polymorphisms. PMID- 27181227 TI - Treatment of alkali-injured cornea by cyclosporine A-loaded electrospun nanofibers - An alternative mode of therapy. AB - In this study we tried to develop a new approach to suppress inflammation and neovascularization in the alkali-injured rabbit cornea. For this reason Cyclosporine A (CsA)-loaded electrospun nanofibers were transferred onto the ocular surface injured with alkali (0.25 N NaOH). Damaged corneas were divided into the following groups: untreated, treated with CsA eye drops, treated with nanofibers drug-free and treated with CsA-loaded nanofibers. Healthy rabbit corneas served as controls. Drug-free nanofibers and CsA-loaded nanofibers were transferred onto the damaged corneal surface immediately after the injury and sutured to conjunctiva. On day five after the injury the nanofibers were removed. The animals from all groups were sacrificed on day twelve after the injury. The extent of the inflammatory reaction and corneal healing were examined macroscopically, immunohistochemically and biochemically. The central corneal thickness was measured using an ultrasonic pachymeter. When compared with untreated injured corneas, injured corneas treated with drug-free nanofibers or injured corneas treated with CsA eye drops, the number of CD3-positive cells (T lymphocytes) and the production of pro-inflammatory cytokines were strongly reduced in corneas treated with CsA-loaded nanofibers, which was associated with the significantly decreased expression of matrix metalloproteinase 9, inducible nitric oxide synthase, vascular endothelial growth factor and active caspase-3. CsA-loaded nanofibers effectively suppressed corneal inflammation and corneal neovascularization. Central corneal thickness restored to levels before injury only in corneas treated with CsA-loaded nanofibers. Corneal transparency was highly restored in these corneas. It is suggested that the beneficial effect of CsA-loaded nanofibers was associated with the continuous release of CsA from nanofibers and continuous affection of damaged cornea by CsA. The suture of nanofibers to conjunctiva and the closed eyes contributed to beneficial corneal healing. This is in contrast to CsA eye drops, which are quickly washed from the ocular surface and the contact of CsA with the damaged cornea was limited. In conclusion, the approach with CsA-loaded nanofibers could represent an effective alternative mode of therapy for corneal chemical burns. PMID- 27181226 TI - Dimethylarginine dimethylaminohydrolase-2 deficiency promotes vascular regeneration and attenuates pathological angiogenesis. AB - Ischemia-induced angiogenesis is critical for tissue repair, but aberrant neovascularization in the retina causes severe sight impairment. Nitric oxide (NO) has been implicated in neovascular eye disease because of its pro-angiogenic properties in the retina. Nitric oxide production is inhibited endogenously by asymmetric dimethylarginines (ADMA and L-NMMA) which are metabolized by dimethylarginine dimethylaminohydrolase (DDAH) 1 and 2. The aim of this study was to determine the roles of DDAH1, DDAH2, ADMA and L-NMMA in retinal ischemia induced angiogenesis. First, DDAH1, DDAH2, ADMA and L-NMMA levels were determined in adult C57BL/6J mice. The results obtained revealed that DDAH1 was twofold increased in the retina compared to the brain and the choroid. DDAH2 expression was approximately 150 fold greater in retinal and 70 fold greater in choroidal tissue compared to brain tissue suggesting an important tissue-specific role for DDAH2 in the retina and choroid. ADMA and L-NMMA levels were similar in the retina and choroid under physiological conditions. Next, characterization of DDAH1(+/-) and DDAH2(-/-) deficient mice by in vivo fluorescein angiography, immunohistochemistry and electroretinography revealed normal neurovascular function compared with wildtype control mice. Finally, DDAH1(+/-) and DDAH2(-/-) deficient mice were studied in the oxygen-induced retinopathy (OIR) model, a model used to emulate retinal ischemia and neovascularization, and VEGF and ADMA levels were quantified by ELISA and liquid chromatography tandem mass spectrometry. In the OIR model, DDAH1(+/-) exhibited a similar phenotype compared to wildtype controls. DDAH2 deficiency, in contrast, resulted in elevated retinal ADMA which was associated with attenuated aberrant angiogenesis and improved vascular regeneration in a VEGF independent manner. Taken together this study suggests, that in retinal ischemia, DDAH2 deficiency elevates ADMA, promotes vascular regeneration and protects against aberrant angiogenesis. Therapeutic inhibition of DDAH2 may therefore offer a potential therapeutic strategy to protect sight by promoting retinal vascular regeneration and preventing pathological angiogenesis. PMID- 27181229 TI - Prognosis and progress in immunotherapies for organ involvements in systemic autoimmune diseases. AB - Treatment of organ involvements accompanied by systemic autoimmune diseases is still challenging for clinicians, reminding the existence of unmet needs. Among them, lupus nephritis (LN), neuropsychiatric lupus, interstitial lung diseases (ILD) complicated with polymyositis/dermatomyositis (PM/DM) or systemic sclerosis (SSc) are the most severe conditions with poor prognosis. Because of the rarity and severity of the disease status, and of variety in evaluation methods, randomized clinical trials tend to be difficult in recruiting patients, in designing protocols, and in meeting primary endpoints. In such tough conditions, superiority of IVCY over corticosteroids alone for LN has been established, which is now going to be replaced by mycophenolate mofetil (MMF). Moreover, non inferiority of tacrolimus to MMF is reported and efficacy of biologics such as Rituximab and Abatacept for LN is under investigation. In contrast, PM/DM-ILD is not suitable for randomized controlled trial because of the severity/acute progression in some patients. Intensive immunosuppressive regimen is recommended for those with poor prognostic factor(s). Cyclophosphamide has limited efficacy in SSc-ILD. Hematopoietic stem cell transplantation elongated patient survival and improved ILD, but with high treatment-related mortality rate. Efficacy of rituximab and MMF has been reported in small-sized trials. In this review, previously established treatment as well as emerging immunotherapies for organ involvements will be discussed. Our experiences in autoimmune settings also will be introduced. PMID- 27181230 TI - Cancer immunotherapy and immunological memory. AB - Human immunological memory is the key distinguishing hallmark of the adaptive immune system and plays an important role in the prevention of morbidity and the severity of infection. The differentiation system of T cell memory has been clarified using mouse models. However, the human T cell memory system has great diversity induced by natural antigens derived from many pathogens and tumor cells throughout life, and profoundly differs from the mouse memory system constructed using artificial antigens and transgenic T cells. We believe that only human studies can elucidate the human immune system. The importance of immunological memory in cancer immunotherapy has been pointed out, and the trafficking properties and long-lasting anti-tumor capacity of memory T cells play a crucial role in the control of malignant tumors. Adoptive cell transfer of less differentiated T cells has consistently demonstrated superior anti-tumor capacity relative to more differentiated T cells. Therefore, a human T cell population with the characteristics of stem cell memory is thought to be attractive for peptide vaccination and adoptive cell transfer. A novel human memory T cell population that we have identified is closer to the naive state than previous memory T cells in the T cell differentiation lineage, and has the characteristics of stem-like chemoresistance. Here we introduce this novel population and describe the fundamentals of immunological memory in cancer immunotherapy. PMID- 27181228 TI - T follicular helper (Tfh) cells in autoimmune diseases. AB - Systemic autoimmune diseases are characterized by multiple organ damages, whose pathogenesis caused by the activation of autoreactive T cells reacting against antigens of the body's own tissues and B cells producing autoantibodies. Following the animal studies, Tfh cells have been identified as a critical subset for the formation and function of B cell responses in humoral immunity, but also play an important role in autoimmunity. In fact, circulating Tfh cells are reported to increase and correlate with disease activity and autoantibody production in human autoimmune diseases. However, the evidence from human studies highlighted apparent differences between mouse and human Tfh cell differentiation. Furthermore, there is increased recognition of functional plasticity and diversity of Tfh cells. This may be advantageous in terms of host defense but needs to be borne in mind in thinking about effective therapies for autoimmune diseases. Thus, better understanding of the extrinsic and intrinsic signals that control plasticity and diversity of Tfh cells will have important therapeutic applications to control autoimmunity. PMID- 27181231 TI - Autoimmune disease and epigenome regulation. AB - Epigenetic modifications play a central role in the cellular programming of gene expression. Two of the most characterized epigenetic modifications are DNA methylation and histone modification. Recent observation that a number of GWAS SNP for immunological diseases localize to immune enhancers suggests the importance of epigenetic modifications that control enhancer activity. Epigenome wide analysis of DNA-methylation in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) revealed differential DNA methylation in a number of disease-related gene pathways. With regard to histone mark, the requirement of millions of cells for established protocol prevents application to clinical samples. However, recent technical advances enable us to capture open chromatin in small amount of patient samples. As epigenetic modifications function as an integrator of environmental stimulation and the underlying genetic variant, detailed epigenetic analysis combined with genetic and environmental factors may facilitate the understanding of the progression of human immunological diseases. PMID- 27181232 TI - A review of adverse events caused by immune checkpoint inhibitors. AB - There has been no effective therapy in the unresectable melanoma for more than 40 years. Anti-PD-1 antibody and anti-CTLA-4 antibody have totally changed the situation. They have clearly shown the survival benefits of the patients with metastatic melanoma. However, immune checkpoint inhibitors sometimes induce various kinds of immune-related adverse events (irAEs). It is very important for the clinicians to know the reported cases of irAEs and to keep in mind the symptoms of irAEs for the early detection. This review describes the previously reported irAEs and adequate managements for irAEs induced by immune checkpoint inhibitors. PMID- 27181233 TI - Assessment of disease activity in rheumatoid arthritis by multi-biomarker disease activity (MBDA) score. AB - For assessing clinical disease activity in rheumatoid arthritis (RA), several composite measures of physical findings, patents'/evaluators' visual analog scales, and acute phase reactants has been used, contributing to advance in therapies through many clinical trials. However, more objective indices have been desired due to subjectivity in conventional indices. The Multi-Biomarker Disease Activity (MBDA) score is a novel blood-test based disease activity score of single integer ranging 1-100, derived from pre-specified algorithms in combination with 12 serum biomarkers (VCAM-1, EGF, VEGF-A, IL-6, TNF-RI, YKL-40, MMP-1, MMP-3, leptin, resistin, SAA, CRP). The MBDA score not only reflects disease activity in RA, but also is predictive for radiographic progression and risk of flare after drug reduction. Herein we review clinical usefulness of the MBDA score in RA. PMID- 27181234 TI - Salivary epidermal growth factor (EGF) in Sjogren's syndrome: association between salivary EGF levels and the severity of intraoral manifestations. AB - Sjogren's syndrome (SS) is a chronic inflammatory autoimmune disease characterized by lymphocytic infiltration of the exocrine glands, especially the salivary and lacrimal glands. As a result of salivary gland dysfunction, most patients with SS have xerostomia, related to a reduced salivary flow rate. In addition to the discomfort due to xerostomia, dry mouth can cause various intraoral manifestations such as refractory stomatitis, ulcer and atrophic changes in the oral mucosa and tongue, and patients' quality of life (QOL) is impaired severely. These manifestations are believed to be caused mainly by a decrease in the clearance in the oral cavity owing to hyposalivation. However, since saliva has several beneficial physiological effects on the intraoral environment, qualitative changes in sialochemistry should also be considered a cause of the refractory intraoral manifestations in SS. Salivary epidermal growth factor (EGF) is considered an important cytoprotective factor against injuries, and it contributes to wound healing in the oral cavity. We evaluated changes in salivary EGF levels and assessed the association between salivary EGF levels and the severity of intraoral manifestations in SS patients. The results showed that the salivary EGF levels decreased with the progression of SS, and this deterioration in saliva quality as well as hyposalivation could play a role in the pathogenesis of refractory intraoral manifestations in SS patients. Our findings provide new target for therapeutic intervention in SS. PMID- 27181235 TI - The effects of TGF-betas on immune responses. AB - Transforming growth factor (TGF)-beta family is a cytokine family with various biological processes and forms a highly homologous group of three mammalian isoforms, TGF-beta1, TGF-beta2, and TGF-beta3. Most of the attention on TGF-beta family in immunology has been mainly focused on TGF-beta1 in that TGF-beta1 induces anti-inflammatory regulatory T cells (Treg), and inflammatory T helper 17 (Th17) cells in combination with interleukin-6. Although little attention has been focused on the immunological roles of TGF-beta2 and TGF-beta3, the function of TGF-beta3 for maintaining immunological homeostasis has recently been identified such as the induction of Th17 cells and direct regulatory effects on humoral immunity. TGF-beta1 and TGF-beta3 shares similar anti-inflammatory or pro inflammatory functions, but exhibits significantly different effects on fibrosis and chondrogenesis. For the clinical application of TGF-betas, the mechanisms by which each TGF-beta isoform regulates immunity has to be elucidated. In this review, we provide an overview of the effects, cellular targets, and therapeutic potential of TGF-betas on immune responses and autoimmune diseases. PMID- 27181236 TI - Altered composition of gut microbiota in rheumatoid arthritis patients. AB - Manifestation of rheumatoid arthritis (RA) can be attributed to both genetic and environmental factors. Some researchers have been focusing on intestinal microbiota which is thought to be one of the environmental factors that may enhance the development of RA. The advancement of culture-independent, high throughput microbial DNA sequencing had enabled us to understand the interplay between intestinal microbiota and host immune systems. In this study, we have reviewed the previous findings in animal and human studies with respect to the role of intestinal microbiota in RA. Mouse models of arthritis have demonstrated that gut microbiota plays a critical role in the disease development. K/BxN and IL-1 receptor-antagonist knock-out mice did not develop disease in germ free condition, however, colonization of particular intestinal bacteria was sufficient to induce arthritis. Moreover, the dysbiosis was observed in the human RA patients from United States, China and Finland. Thus, we believe that endeavors to improve the dysbiosis would serve as a novel therapeutic or preventive strategy in RA patients. PMID- 27181237 TI - Successful treatment by rituximab in a patient with TAFRO syndrome with cardiomyopathy. AB - TAFRO syndrome is a newly defined disease entity which is characterized by thrombocytopenia, anasarca, myelofibrosis, renal dysfunction, and organomegaly. A histological pattern of multiple lymphadenopathy of atypical Castleman's disease (CD) is also an important characteristic. A 48-year-old man was referred to our hospital with fever, asthenia, bilateral pleural effusion, ascites, generalized edema, dyspnea, hypoalbuminemia, severe thrombocytopenia, anemia, renal failure and proteinuria, whereas bacterial culture and serological and PCR tests for various viruses were all negative. A CT scan showed multiple lymphadenopathy and tissue sampling of inguinal lymph nodes showed a compatible histology with plasma cell type CD. A diagnosis of TAFRO syndrome was made. Ten days after hospitalization, sudden cardiac insufficiency and anuria developed. Despite glucocorticoid pulse therapy, tocilizumab and plasmapheresis, clinical and laboratory features did not improve. On the 34(th) hospital day, we started rituximab. His general condition started to improve in several days, and by one month later anasarca had improved drastically. Thrombocytopenia and renal function gradually improved and finally normalized. Cardiac motion also improved. This is the first report of a TAFRO syndrome patient with cardiomyopathy, who was successfully treated with rituximab. PMID- 27181238 TI - A case of familial Mediterranean fever who complained of periodic fever and abdominal pain diagnosed by MEFV gene analysis. AB - Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disease caused by Mediterranean FeVergene (MEFV) mutations on Chromosome 16, and characterized by periodic fever of and serositis. FMF is the result of gain-of function mutations in pyrin that lead to interleukin-1beta activation. FMF can be classified as "typical" and "atypical" types based on clinical finding and genetic screening. Although MEFV genotyping has enabled FMF to be confirmed in some cases, the diagnosis remains predominantly clinical since genotyping has shown that the disease is characterized by variable manifestations in Japanese. In 1976, the first report performed on the case of Japanese FMF with periodic fever of and serositis. Since 2002, genetic analyses are performed on Japanese FMF patients by K. Shiozaki et al. and N. Tomiyama et al. In our case, she was a 25-year-old Japanese woman with at periodic fever and abdominal pain. MEFV gene analysis demonstrated a heterozygous mutation of variant M694I, leading to a diagnosis of FMF. After the increase dose (up to 3 mg/day) of colchicine, periodic fever and abdominal pain disappeared. It is the important candidate of FMF for differential diagnosis with unexplained periodic fever and serositis, such as our case. PMID- 27181239 TI - Misfolded proteins complexed with MHC class II molecules are targets for autoantibodies. AB - Major histocompatibility complex (MHC) molecule is important for immune system through its function of presentation of peptide antigens. MHC is the gene most strongly associated with susceptibility to many autoimmune diseases. We recently found a novel function of MHC class II molecules to transport cellular misfolded proteins to the cell surface without processing to peptides. Interestingly, misfolded proteins transported to the cell surface by MHC class II molecules were found to be a specific targets for autoantibodies produced in patients with autoimmune diseases such as rheumatoid arthritis and antiphospholipid syndrome. Furthermore, autoantibody binding to misfolded proteins complexed with MHC class II molecules is strongly associated with the susceptibility to autoimmune diseases conferred by each MHC class II allele. Therefore, misfolded proteins associated with MHC class II molecules might be involved in the pathogenesis of autoimmune diseases. PMID- 27181240 TI - Allergic bronchopulmonary aspergillosis in a patient with rheumatoid arthritis under adalimumab therapy: a case report. AB - A 77-year-old woman with a 15-year history of rheumatoid arthritis (RA) was admitted to our hospital because of a wet cough that persisted for 1 month. The patient had been taking methotrexate (MTX) and adalimumab (ADA) for the past 3 years, and disease activity of RA was low. Discontinuation of ADA and MTX and treatment with oral levofloxacin were not effective. On admission, laboratory examinations showed eosinophilia (2539/MUL), elevated serum total immunoglobulin E (538.0 IU/ml) and Aspergillus-specific immunoglobulin E levels, and Aspergillus fumigatus serum precipitins. A chest radiograph revealed multiple bilateral pulmonary shadows, and computed tomography revealed multiple consolidations. Bronchoscopic examination showed mucous plugs. Pathological examination revealed diffuse infiltration of eosinophils and fungus in the plugs. These findings led to the diagnosis of allergic bronchopulmonary aspergillosis (ABPA). A combination of prednisolone (0.5 mg/kg/day) and itraconazole (200 mg/day) was administered. After 3 months, the pulmonary consolidations resolved. To our knowledge, this is the first report of ABPA in a patient with RA treated with ADA. If patients treated with biologic disease-modifying antirheumatic drugs present with eosinophilia and pulmonary consolidations, clinicians should consider ABPA in the differential diagnosis. PMID- 27181241 TI - Overactive Bladder and Storage Lower Urinary Tract Symptoms Following Radical Prostatectomy. AB - OBJECTIVE: To describe the rate of overactive bladder (OAB) and storage lower urinary tract symptoms following radical prostatectomy (RP) and determine if subsequent radiation increases the risk of OAB. METHODS: We reviewed all patients who underwent open RP at our tertiary care institution from January 2006 to June 2011. Primary outcomes were the proportion of patients with new OAB and time to development of OAB in those treated with RP alone vs RP plus radiation. Secondary outcomes included the proportion of patients treated for OAB. A Cox survival analysis was used to assess the impact of radiation on development of OAB. RESULTS: Of the 875 patients who met study criteria, 19% of patients developed de novo OAB defined as urgency with or without frequency and nocturia. A total of 256 patients (29%) developed 1 or more urinary symptoms including nocturia (22%), frequency (21%), urgency (19%), and urge incontinence (6%) following RP. After adjusting for age, body mass index, smoking status, cancer stage, and nerve sparing status, radiation therapy was associated with an increased relative hazard of OAB (5.59; 95% CI 3.63-8.61, P < .001). Among men classified with de novo OAB, only 41% received treatment. CONCLUSION: OAB and storage lower urinary tract symptoms are prevalent in men post-RP. Adjuvant or salvage radiation therapy increases the risk of developing OAB after RP. OAB may be undertreated in men following prostate cancer treatment. PMID- 27181242 TI - Iatrogenic Bladder Injury: National Analysis of 30-Day Outcomes. AB - OBJECTIVE: To examine the risk factors and outcomes of BI, a rare complication of abdominopelvic surgery. METHODS: We queried the National Surgical Quality Improvement Program database to identify intraoperative bladder injury (BI) defined by the Current Procedural Terminology code for cystorrhaphy from 2005 to 2013. Propensity-score matching balanced the differences between patients with BI and the controls. The factors matched included age, body mass index, race, modified frailty index, and procedure category. RESULTS: There were 1685 cases of BI in 1,541,736 surgeries (0.11%). Although 49.5% of surgeries were performed in an open fashion, this approach accounted for 69.3% of BI (P < .001). Prior to matching, mortality rates and morbidity were increased for the BI group (P < .001). Moreover, age, recent chemotherapy or radiation or steroid history, and smoking were among the risk factors for BI (all P < .05). Resident involvement increased the odds of BI and complications after BI, but decreased the risk of readmission (all P < .05). After matching, 30-day mortality was no longer increased for patients with BI (P < .001). Patients with BI requiring repair did have increased median length of stay (6 days [interquartile range {IQR}: 3-11] vs 5 [IQR: 2-9]; P < .001) and operative time (203 min [IQR: 140-278] vs 134 [IQR: 86-199]; P < .001). BI patients were more likely to undergo reoperation (7.7% vs 5.3%; P = .005). Urine infection, sepsis, and bleeding were more likely in the BI group compared with the matched controls (all P < .001). Delayed repair was rare. CONCLUSION: We present the largest national series assessing iatrogenic BI and subsequent repair. BI increases 30-day complications, reoperation, and length of stay but does not increase 30-day mortality compared with matched controls. More complex surgical cases and increased baseline comorbidity were risk factors for BI. PMID- 27181243 TI - Meatal Mobilization and Glanuloplasty: A Viable Option for Coronal and Glanular Hypospadias Repair. AB - OBJECTIVE: To present the meatal mobilization with glanuloplasty inclusive (MMGPI) modification of meatal advancement and glanuloplasty inclusive. MATERIALS AND METHODS: A total of 120 patients with anterior hypospadias underwent MMGPI between September 2008 and October 2014 at Kermanshah University of Medical Sciences. Satisfactory outcomes were defined as continuous straight urinary flow and catheterization of new meatus without difficulty. Cosmetic outcomes were considered acceptable if patients maintained a slit-like meatus at the glanular tip. Patients were examined at 1 week, 1, 3, 6, 12, and 24 months. RESULTS: The 120 patients with anterior hypospadias underwent MMGPI. There were no hematoma, meatal necrosis, or other early complications. In patients with glanular hypospadias, there were no meatal regressions or stenosis, all voiding patterns were normal, and all patients maintained a slit-like meatus at the glanular tip. Two patients with coronal hypospadias had meatal stenosis and 2 patients had meatal regression. Five patients with sub-coronal hypospadias had 2-mm meatal regression with downward sloping urinary stream, and 2 patients had meatal stenosis. In all, meatus remained distal to the preoperative meatus with no necrosis. Small sample size was the major limitation of this study. CONCLUSION: MMGPI represents a viable option for glanular and coronal hypospadias repair. PMID- 27181244 TI - Bilateral Orbital Metastasis of Prostatic Adenocarcinoma. AB - Despite the high incidence of prostate carcinoma, metastases of the uvea are very rare and bilateral localization is even more. We report here the case of a 77 year-old man diagnosed with a metastatic prostate carcinoma. Two months later, he presented a decreased vision in his right eye and blurred vision in the left eye relevant to metastatic lesion on his right iris and left choroidal metastasis. The urologist should evoke possibility of ocular metastasis in patients with prostate cancer presenting visual disorders. PMID- 27181245 TI - Wooden Foreign Body in the Renal Pelvis. AB - Migration of foreign bodies into the renal collecting system is very rare and usually concerns iatrogenically implanted objects. Migration of a foreign body from the gastrointestinal tract to the kidneys is even more rare. We present a case of migration of a wooden toothpick from the duodenum into the pelvis of the right kidney. The patient was not aware that he swallowed a toothpick; the foreign body resulted in hematuria and flank pain. The toothpick was missed during the initial computed tomography urography. Correct diagnosis was revealed by follow-up computed tomography. The toothpick was extracted endoscopically. PMID- 27181246 TI - Production and characterization of a biotinylated single-chain variable fragment antibody for detection of parathion-methyl. AB - In this article, we reported the development of a biotinylated single-chain variable fragment (scFv) antibody based indirect competitive enzyme-linked immunosorbent assay (IC-ELISA) for parathion-methyl (PM) detection. Firstly, a phage display library was generated using a pre-immunized BALB/C mouse against a specific hapten of PM. After four rounds of panning, the scFv gene fragments were transferred into a secreted expression vector. Then, the scFv antibodies were secreted expressed and screened by IC-ELISA against PM. The selected scFv antibody was fused with a biotin acceptor domain (BAD) and inserted into pET 28a(+) vector for high-level expression in Escherichia coli BL2 (DE3). After optimizing expression conditions, the scFv-BAD antibody was expressed as a soluble protein and biotinylated in vitro by the E. coli biotin ligase (BirA). Subsequently, the biotinylated scFv-BAD antibody was purified with a high yield of 59.2 +/- 3.7 mg/L of culture, and was characterized by SDS-PAGE and western blotting. Finally, based on the biotinylated scFv-BAD, a sensitive IC-ELISA for detection of PM was developed, and the 50% inhibition value (IC50) of PM was determined as 14.5 ng/mL, with a limit of detection (LOD, IC10) of 0.9 ng/mL. Cross-reactivity (CR) studies revealed that the scFv antibody showed desirable specificity for PM. PMID- 27181247 TI - Friction and Surface Temperature of Wet Hair Containing Water, Oil, or Oil-in Water Emulsion. AB - The surface properties and the tactile texture of human hair are important in designing hair-care products. In this study, we evaluated the temporal changes of friction and temperature during the drying process of wet human hair containing water, silicone oil, or oil-in-water (O/W) emulsion. The wet human hair including water or O/W emulsion have a moist feel, which was caused by the temperature reduction of approximately 3-4 degrees C. When human hair is treated with silicone oil, more than 60% of the subjects felt their hair to be slippery and smooth like untreated hair. Treating hair with O/W emulsion after drying made the subject perceive a slippery feeling because the surfactant reduced friction on the hair surface. These results indicated that both friction and thermal properties of the hair surface are important to control the tactile texture of the human hair. PMID- 27181248 TI - Inhibition of Frying Oil Oxidation by Carbon Dioxide Blanketing. AB - The oxidation of oil starts, in general, from the penetration of atmospheric oxygen into oil. Inhibition of the vigorous oxidation of oil at deep-frying temperature under carbon dioxide flow, by disrupting the contact between oil and air, was first demonstrated using oil in a round bottom flask. Next, the minimum carbon dioxide flow rate necessary to blanket 4 L of frying oil in an electric fryer (surface area 690 cm(2)) installed with nonwoven fabric cover, was found to be 40 L/h. Then deep-frying of potato was done accordingly; immediately after deep-frying, an aluminum cover was placed on top of the nonwoven fabric cover to prevent the loss of carbon dioxide and the carbon dioxide flow was shut off. In conclusion, the oxidation of oil both at deep-frying temperature and during standing was remarkably inhibited by carbon dioxide blanketing at a practical flow rate and volume. Under the deep-frying conditions employed in this study, the increase in polar compound content was reduced to half of that of the control. PMID- 27181249 TI - Surface Adsorption and Micelle Formation of Polyoxyethylene-type Nonionic Surfactants in Mixtures of Water and Hydrophilic Imidazolium-type Ionic Liquid. AB - The interfacial properties of polyoxyethylene alkyl ether-type nonionic surfactants (CnEm) were studied in a hydrophilic room-temperature ionic liquid, 1 butyl-3-methylimidazolium tetrafluoroborate (bmimBF4), in the presence of water. These properties were assessed using static surface tension, pyrene fluorescence, and dynamic light scattering measurements. The interfacial properties were strongly dependent on the solution composition. Increased water concentration lowered the critical micelle concentration (cmc). The cmc was also affected by the lengths of both the alkyl and polyoxyethylene chains, but a greater impact was observed for the alkyl chain length. These results indicate that micellization occurs as a result of solvophobic interaction between surfactant molecules in the water/bmimBF4 mixed solutions, similar to aqueous surfactant systems. The cloud point phenomenon was observed for CnEm with a relatively low hydrophilic-lipophilic balance (HLB) value, and the relationship between the cloud point and water/bmimBF4 composition exhibited a convex upward curve. Furthermore, the mixing of bmimBF4 with water increased the surfactant solubility for water-rich compositions, suggesting that bmimBF4 acts as a chaotropic salt. PMID- 27181250 TI - Kinetic and Thermodynamics studies for Castor Oil Extraction Using Subcritical Water Technology. AB - In this work both kinetic and thermodynamics of castor oil extraction from its seeds using subcritical water technique were studied. It was found that the extraction process followed two consecutive steps. In these steps, the oil was firstly extracted from inside the powder by diffusion mechanism. Then the extracted oil, due to extending the extraction time under high temperature and pressure, was subjected to a decomposition reaction following first order mechanism. The experimental data correlated well with the irreversible consecutive unimolecular-type first order mechanism. The values of both oil extraction rate constants and decomposition rate constants were calculated through non-linear fitting using DataFit software. The extraction rate constants were found to be 0.0019, 0.024, 0.098, 0.1 and 0.117 min(-1), while the decomposition rate constants were 0.057, 0.059, 0.014, 0.019 and 0.17 min(-1) at extraction temperatures of 240, 250, 260, 270 and 280 degrees C, respectively. The thermodynamic properties of the oil extraction process were investigated using Arrhenius equation. The values of the activation energy, Ea, and the frequency factor, A, were 73 kJ mol(-1) and 946, 002 min(-1), respectively. The physicochemical properties of the extracted castor oil including the specific gravity, viscosity, acid value, pH value and calorific value were found to be 0.947, 7.487, 1.094 mg KOH/g, 6.1, and 41.5 MJ/Kg, respectively. Gas chromatography analysis showed that ricinoleic acid (83.6%) appears as the predominant fatty acid in the extracted oil followed by oleic acid (5.5%) and linoleic acid (2.3%). PMID- 27181251 TI - Oligosaccharide-based Surfactant/Citric Acid Buffer System Stabilizes Lactate Dehydrogenase during Freeze-drying and Storage without the Addition of Natural Sugar. AB - Experiments were conducted to assess the maintenance effects of oligosaccharide based surfactants on the enzymatic activity of a model protein, lactate dehydrogenase (LDH), during freeze-drying and room temperature storage using the citric acid buffer system. Oligosaccharide-based surfactants, which exhibit a high glass transition temperature (Tg), promoted the eminent retention of enzymatic activity during these protocols, whereas monosaccharide-based surfactants with a low Tg displayed poor performance at high concentration, albeit much better than that of Tween 80 at middle concentration. The increase in the alkyl chain length did not exert positive effects as observed for the maintenance effect during freeze-thawing, but an amphiphilic nature and a glass forming ability were crucial for the effective stabilization at a low excipient concentration during freeze-drying. Even a low oligosaccharide-based surfactant content (0.1 mg mL(-1)) could maintain LDH activity during freeze-drying, but a high surfactant content (1.0 mg mL(-1)) was required to prevent buffer precipitation and retain high LDH activity on storage. Regarding storage, glass formation restricted molecular mobility in the lyophilized matrix, and LDH activity was effectively retained. The present results describe a strategy based on the glass-forming ability of surfactant-type excipients that affords a natural sugar-free formulation or an alternative use for polysorbate-type surfactants. PMID- 27181252 TI - Imperata cylindrica sp as Novel Silica-Based Heterogeneous Catalysts for Transesterification of Palm Oil Mill Sludge. AB - Biodiesel from palm oil mill sludge (POMS) was prepared in the presence of novel silica-based heterogeneous catalysts derived from Imperata cylindrica sp. Imperatacid and Imperatabase are two types of heterogeneous catalysts derived from Imperata cylindrica sp and characterized using scanning electron microscopy, Energy Dispersive X-ray, Brunauer-Emmett-Teller surface area and pore size measurement. Imperatacid has particle size of 43.1-83.9 um while Imperatabase in the range of 89-193 um. Imperatacid was conveniently applied in esterification step to afford > 90 wt% oil in 1:3 (oil/methanol) and 10 wt% catalyst, followed by transesterification with 1 wt% Imperatabase and 1:1 (oil/methanol) for 1 h at 65 degrees C to afford 80% biodiesel with higher percentage of methyl palmitate (48.97%) and methyl oleate (34.14%) compare to conventional homogeneous catalyst. Reusability of the catalyst up to three times afforded biodiesel ranging from 78 80% w/w. The biodiesel was demonstrated onto alternative diesel engine (Megatech((r))-Mark III) and showed proportional increased of torque (r) to biodiesel loading. PMID- 27181253 TI - Antioxidative Properties of Stearoyl Ascorbate in a Food Matrix System. AB - Stearoyl ascorbate or 6-O-stearoyl l-ascorbate is a lipophilic derivative of l ascorbic acid and is commercially used in foods as a fat-soluble antioxidant and surfactant to overcome the disadvantages of using l-ascorbic acid. The objective of this research is to evaluate the antioxidative ability of stearoyl ascorbate, in the presence of wheat starch or gluten as a matrix, by measuring the unoxidized methyl linoleate available in the mixture of them after oxidation under accelerated conditions compared to that when using ascorbic acid. We observed that stearoyl ascorbate and ascorbic acid exhibited mutually adjacent antioxidative ability against oxidation of the methyl linoleate at a molar ratio of 0.0001 in presence of either wheat starch or gluten. In addition, the oxidation process in the mixture containing either stearoyl ascorbate or ascorbic acid was significantly slower than that in the mixture without stearoyl ascorbate or ascorbic acid. Moreover, by altering the initiation and propagation periods of the oxidation process, the mixture containing the stearoyl ascorbate and gluten as the matrix exhibited conspicuously slower oxidation than the mixture containing either the wheat starch or stearoyl ascorbate alone. However, increase in the ratio of stearoyl ascorbate to methyl linoleate to 0.001 or higher resulted in adverse effects due to acceleration of the oxidation process. PMID- 27181254 TI - Japanese study of tofogliflozin with type 2 diabetes mellitus patients in an observational study of the elderly (J-STEP/EL): A 12-week interim analysis. AB - AIMS/INTRODUCTION: Sodium-glucose co-transporter 2 inhibitors are a promising treatment for type 2 diabetes mellitus, but are associated with concerns about specific adverse drug reactions. We carried out a 1-year post-marketing surveillance of tofogliflozin, a novel agent in this class, in Japanese elderly patients with type 2 diabetes mellitus and here report the results of a 12-week interim analysis, focusing on adverse drug reactions of special interest. MATERIALS AND METHODS: The present prospective observational study included all type 2 diabetes mellitus patients aged >=65 years who started tofogliflozin during the first 3 months after its launch. Data on demographic and baseline characteristics, clinical course and adverse events were collected. RESULTS: Of 1,535 patients registered, 1,506 patients whose electronic case report forms were collected and who had at least one follow-up visit were included in the safety analysis at 12 weeks. A total of 178 of 1,506 patients (11.82%) had at least one adverse drug reaction to tofogliflozin. The incidence of adverse drug reactions of special interest (polyuria/pollakiuria, volume depletion-related events, urinary tract infection, genital infection, skin disorders and hypoglycemia) was 2.19, 2.32, 1.33, 1.13, 1.46 and 0.73%, respectively. No new safety concerns were identified. Among those evaluable for clinical effectiveness, the mean (standard deviation) glycated hemoglobin decreased from 7.65% (1.35%) at baseline to 7.25% (1.16%) at 12 weeks by 0.39% (0.94%; P < 0.0001). CONCLUSIONS: This interim analysis characterized the safety profile of tofogliflozin in Japanese elderly patients with type 2 diabetes mellitus during the early post-marketing period. PMID- 27181255 TI - A three-terminal ultraviolet photodetector constructed on a barrier-modulated triple-layer architecture. AB - We report a novel three-terminal device fabricated on MgZnO/ZnO/MgZnO triple layer architecture. Because of the combined barrier modulation effect by both gate and drain biases, the device shows an unconventional I-V characteristics compared to a common field effect transistor. The photoresponse behavior of this unique device was also investigated and applied in constructing a new type ultraviolet (UV) photodetector, which may be potentially used as an active element in a UV imaging array. More significantly, the proper gate bias-control offers a new pathway to overcome the common persistent photoconductivity (PPC) effect problem. Additionally, the MgZnO:F as a channel layer was chosen to optimize the photoresponse properties, and the spectrum indicated a gate bias dependent wavelength-selectable feature for different response peaks, which suggests the possibility to build a unique dual-band UV photodetector with this new architecture. PMID- 27181256 TI - Electroencephalographic findings in schizophreniform and affective disorders. AB - OBJECTIVE: Pathological findings in electroencephalography (EEG) are discussed as a possible marker of organic mental disorders and a therapeutic response to anticonvulsive medication under these conditions. METHODS: We compared the prevalence of EEG abnormalities in 100 patients with schizophrenia, 100 patients with schizoaffective disorder, 51 patients with acute polymorphic psychotic disorder, 100 patients with bipolar disorder, 100 patients with unipolar major depression and 76 healthy control subjects with the findings of a previous study using well-diagnosed, large control samples (13,658 pilots and aircrew personnel). RESULTS: We detected an increased number of pathological EEG findings with intermittent rhythmic delta or theta activity in 7% of patients with schizophrenia, 7% of patients with schizoaffective disorder, 5.9% of patients with acute polymorphic psychosis, 6% of patients with bipolar disorder, 4% of unipolar depressed patients and 3.9% of the own control group, compared to 1% of strictly controlled healthy subjects. One-sided logistic regression revealed an association between pathological EEGs and the diagnosis of schizophrenia (Wald W = 3.466, p = 0.0315), schizoaffective disorder (W = 3.466, p = 0.0315) and bipolar disorder (W = 2.862, p = 0.0455). CONCLUSIONS: We suggest that the previously developed local area network inhibition model for a potential paraepileptic pathomechanism can explain the relevance of such findings in different psychiatric disorders. PMID- 27181257 TI - Formation of Guaiacol by Spoilage Bacteria from Vanillic Acid, a Product of Rice Koji Cultivation, in Japanese Sake Brewing. AB - The formation of guaiacol, a potent phenolic off-odor compound in the Japanese sake brewing process, was investigated. Eight rice koji samples were analyzed, and one contained guaiacol and 4-vinylguaiacol (4-VG) at extraordinarily high levels: 374 and 2433 MUg/kg dry mass koji, respectively. All samples contained ferulic and vanillic acids at concentrations of mg/kg dry mass koji. Guaiacol forming microorganisms were isolated from four rice koji samples. They were identified as Bacillus subtilis, B. amyloliquefaciens/subtilis, and Staphylococcus gallinarum using 16S rRNA gene sequence. These spoilage bacteria convert vanillic acid to guaiacol and ferulic acid to 4-VG. However, they convert very little ferulic acid or 4-VG to guaiacol. Nine strains of koji fungi tested produced vanillic acid at the mg/kg dry mass koji level after cultivation. These results indicated that spoilage bacteria form guaiacol from vanillic acid, which is a product of koji cultivation in the sake brewing process. PMID- 27181258 TI - Synthesis of Electroneutralized Amphiphilic Copolymers with Peptide Dendrons for Intramuscular Gene Delivery. AB - Intramuscular gene delivery materials are of great importance in plasmid-based gene therapy system, but there is limited information so far on how to design and synthesize them. A previous study showed that the peptide dendron-based triblock copolymer with its components arranged in a reversed biomembrane architecture could significantly increase intramuscular gene delivery and expression. Herein, we wonder whether copolymers with biomembrane-mimicking arrangement may have similar function on intramuscular gene delivery. Meanwhile, it is of great significance to uncover the influence of electric charge and molecular structure on the function of the copolymers. To address the issues, amphiphilic triblock copolymers arranged in hydrophilic-hydrophobic-hydrophilic structure were constructed despite the paradoxical characteristics and difficulties in synthesizing such hydrophilic but electroneutral molecules. The as-prepared two copolymers, dendronG2(l-lysine-OH)-poly propylene glycol2k(PPG2k)-dendronG2(l lysine-OH) (rL2PL2) and dendronG3(l-lysine-OH)-PPG2k-dendronG3(l-lysine-OH) (rL3PL3), were in similar structure but had different hydrophilic components and surface charges, thus leading to different capabilities in gene delivery and expression in skeletal muscle. rL2PL2 was more efficient than Pluronic L64 and rL3PL3 when mediating luciferase, beta-galactosidase, and fluorescent protein expressions. Furthermore, rL2PL2-mediated growth-hormone-releasing hormone expression could significantly induce mouse body weight increase in the first 21 days after injection. In addition, both rL2PL2 and rL3PL3 showed good in vivo biosafety in local and systemic administration. Altogether, rL2PL2-mediated gene expression in skeletal muscle exhibited applicable potential for gene therapy. The study revealed that the molecular structure and electric charge were critical factors governing the function of the copolymers for intramuscular gene delivery. It can be concluded that, combined with the previous study, both structural arrangements either reverse or similar to the biomembrane are effective in designing such copolymers. It also provides an innovative way in designing and synthesizing new electroneutralized triblock copolymers, which could be used safely and efficiently for intramuscular gene delivery. PMID- 27181259 TI - Effect of Hurricane Sandy on Health Care Services Utilization Under Medicaid. AB - OBJECTIVE: This investigation assessed changes in utilization of inpatient, outpatient, emergency department, and pharmacy services in the aftermath of Hurricane Sandy in 8 counties in New York affected by the storm. METHODS: Medicaid data for enrollees residing in 8 counties in New York were used to obtain aggregated daily counts of claims for 4 service types over immediate, 3 month, and 1-year periods following the storm. Negative binomial regression was used to compare service utilization in the storm year with the 2 prior years, within areas differentially affected by the storm. RESULTS: Changes in service utilization within areas inside or outside the storm zone were most pronounced over the 1-year effect period. Differences in service utilization by year were the same by storm zone designation over the immediate effect period for all services. CONCLUSIONS: Results are consistent with previous investigations demonstrating that some of the greatest effects of a disaster on health services utilization occur well beyond the initial event. One-year effects, combined with some 3-month effects, suggests that storm recovery, with its effect on health care services utilization, may have followed different paths in areas designated as inside or outside the storm zone. (Disaster Med Public Health Preparedness. 2016;10:472-484). PMID- 27181260 TI - Treatment of cerebral radiation necrosis with nerve growth factor: A prospective, randomized, controlled phase II study. AB - PURPOSE: A prospective, placebo controlled phase II trial was conducted to test the efficacy of Nerve Growth Factor (NGF) for the treatment of symptomatic temporal lobe necrosis (TLN). MATERIALS AND METHODS: Patients with progressive TLN were randomly assigned to either the control or the study group in a 1:1 ratio. The control group received corticosteroids with gradually reduced dosage. The study group received NGF with corticosteroids. NGF was dissolved in 2mL normal saline and injected intramuscularly at 18MUg/time, once a day for 2months. The efficacy was evaluated by both the objective and subjective methods every 3 4months after treatment. The objective method compared volumes of the necrotic masses on MRI before and after treatment. The subjective method compared the neurocognitive score as evaluated by the mini-mental status examination (MMSE). RESULTS: Twenty-eight cases were enrolled into this study. The objective evaluation showed that the response rate (RR) in the study group was higher than the control group. The ratio was 10 versus 2 (p=0.006), and 12 versus 3 (p=0.002) at 3-4months and 6-8months after intervention, respectively. The subjective evaluation demonstrated both groups were effective in controlling the necrosis related symptoms in the first 6months after treatment. But NGF was more effective than corticosteroids at 9months (13 versus 4, p=0.001). The only observed side effect was mild pain at the injection site in 3 patients in the study group. CONCLUSIONS: Our results demonstrated that the process of TLN is not irreversible. NGF is more effective in recovering TLN than corticosteroids with little side effect. NGF has a longer duration in controlling the necrosis related symptoms than corticosteroids. PMID- 27181261 TI - Transplantation of dental pulp stem cells suppressed inflammation in sciatic nerves by promoting macrophage polarization towards anti-inflammation phenotypes and ameliorated diabetic polyneuropathy. AB - AIMS/INTRODUCTION: Dental pulp stem cells (DPSCs) are thought to be an attractive candidate for cell therapy. We recently reported that the transplantation of DPSCs increased nerve conduction velocity and nerve blood flow in diabetic rats. In the present study, we investigated the immunomodulatory effects of DPSC transplantation on diabetic peripheral nerves. MATERIALS AND METHODS: DPSCs were isolated from the dental pulp of Sprague-Dawley rats and expanded in culture. Eight weeks after the streptozotocin injection, DPSCs were transplanted into the unilateral hindlimb skeletal muscles. Four weeks after DPSC transplantation, neurophysiological measurements, inflammatory gene expressions and the number of CD68-positive cells in sciatic nerves were assessed. To confirm the immunomodulatory effects of DPSCs, the effects of DPSC-conditioned media on lipopolysaccharide-stimulated murine macrophage RAW264.7 cells were investigated. RESULTS: Diabetic rats showed significant delays in sciatic nerve conduction velocities and decreased sciatic nerve blood flow, all of which were ameliorated by DPSC transplantation. The number of CD68-positive monocytes/macrophages and the gene expressions of M1 macrophage-expressed cytokines, tumor necrosis factor alpha and interleukin-1beta, were increased in the sciatic nerves of the diabetic rats. DPSC transplantation significantly decreased monocytes/macrophages and tumor necrosis factor-alpha messenger ribonucleic acid expression, and increased the gene expression of the M2 macrophage marker, CD206, in the sciatic nerves of the diabetic rats. The in vitro study showed that DPSC-conditioned media significantly increased the gene expressions of interleukin-10 and CD206 in lipopolysaccharide-stimulated RAW264.7 cells. CONCLUSIONS: These results suggest that DPSC transplantation promoted macrophages polarization towards anti inflammatory M2 phenotypes, which might be one of the therapeutic mechanisms for diabetic polyneuropathy. PMID- 27181262 TI - Management of bipolar disorder in the intercontinental region: an international, multicenter, non-interventional, cross-sectional study in real-life conditions. AB - Most of the existing data on real-life management of bipolar disorder are from studies conducted in western countries (mostly United States and Europe). This multinational, observational cohort study aimed to describe the management and clinical outcomes of bipolar patients in real-life conditions across various intercontinental countries (Bangladesh, Egypt, Iran, Israel, Tunisia, and Ukraine). Data on socio-demographic and disease characteristics, current symptomatology, and pharmacological treatment were collected. Comparisons between groups were performed using standard statistical tests. Overall, 1180 patients were included. The median time from initial diagnosis was 80 months. Major depressive disorder was the most common initial diagnosis. Mood stabilizers and antipsychotics were the most common drugs being prescribed at the time of the study. Antidepressants (mainly selective serotonin uptake inhibitors [SSRIs]) were administered to 36.1% of patients. Patients with bipolar I disorder received higher number of antipsychotics and anxiolytics than those with bipolar II disorder (p < 0.001). Presence of depressive symptoms was associated with an increase in antidepressant use (p < 0.001). Bipolar disorder real-life management practice, irrespective of region, shows a delay in diagnosis and an overuse of antidepressants. Clinical decision-making appears to be based on a multidimensional approach related to current symptomatology and type of bipolar disorder. PMID- 27181263 TI - [Survey of adolescent perception of hospital admission. The importance of hospital humanisation]. AB - INTRODUCTION: The humanisation of health care involves considering the patient as an integral human being, providing assistance beyond medical care, and covering other fields such as social, emotional, spiritual, or relational areas. OBJECTIVE: To evaluate the requirements and concerns of the hospitalised children. SUBJECTS AND METHOD: A cross-sectional, descriptive study was conducted using an anonymous questionnaire on children aged 12-16. RESULTS: The study included 39 patients, with a median age of 14 years. The most unpleasant experience during the hospitalisation was the invasive procedures. Almost all (95%) of patients suffered from pain, and 17% of them felt at some point that a procedure was performed without them being fully aware. More than 75% of children asked for more entertainment, with the lack of Wi-Fi being the more demanded item. CONCLUSIONS: The needs of the population included in this survey, showed the importance to consider cognitive (necessity of obtaining clear and extensive information), social (maintaining everyday relationships), emotional (illness and its diagnostic and therapeutic procedures often generate mood disorders), and practical (environmental and architectural aspects can lead to either an improvement or a worsening of the hospitalisation perception) factors. All of these factors have shown a beneficial contribution, leading to an earlier recovery of health. PMID- 27181266 TI - Food-choice motives of adolescents in Jakarta, Indonesia: the roles of gender and family income. AB - OBJECTIVE: The aims of the present study were to assess the reliability and validity of the Food Choice Questionnaire (FCQ) and to determine the factors associated with food-choice motives in public junior-high-school students in Jakarta, Indonesia. DESIGN: Cross-sectional study with self-administered questionnaires. Trained research assistants measured height and weight of the participants on the day of the data collection. Settings Fourteen randomly selected public junior-high schools in East Jakarta, Indonesia. SUBJECTS: Public junior-high-school students (n 681) in grades 7 and 8, aged 13-14 years (377 girls and 304 boys). RESULTS: Three food-choice motives (subscales) were obtained from factor analysis and reliability testing: (i) comfort; (ii) convenience and price; and (iii) health. The subscale with the greatest mean value was health. Family affluence was inversely associated with the convenience and price subscale (beta=-0.05, P=0.01) and with the health subscale (beta=-0.04; P=0.02). Females were less likely than males to consider health when choosing foods (beta=-0.16; P=0.03). CONCLUSIONS: While its factor structure differed from those found in previous studies of adults, the FCQ can provide reliable measures of food-choice motives among these adolescents. Students from less affluent families placed more importance on food's convenience and price, but more affluent students did not necessarily make healthier choices. Compared with females, males were more likely to choose healthy foods. Future interventions should be tailored based on the socio-economic status of the target group. PMID- 27181264 TI - A 1-year, prospective, observational study of Japanese outpatients with type 1 and type 2 diabetes switching from insulin glargine or detemir to insulin degludec in basal-bolus insulin therapy (Kumamoto Insulin Degludec Observational study). AB - AIMS/INTRODUCTION: The aim of the present prospective observational study was to assess long-term efficacy and safety of insulin degludec as a part of a basal bolus therapy for Japanese patients with type 1 or type 2 diabetes in routine clinical practice. MATERIALS AND METHODS: In the present study, 93 type 1 diabetes patients and 135 type 2 diabetes patients treated with insulin glargine or detemir were switched from their basal insulin to insulin degludec. The primary end-points were the changes in glycated hemoglobin (HbA1c) from baseline at 3, 6 and 12 months. The secondary end-points were changes in body mass index, insulin dose, frequency of hypoglycemia and adverse events. RESULTS: HbA1c levels from baseline were significantly reduced at 3, 6, and 12 months by 0.4, 0.4 and 0.3% in type 1 diabetes patients, respectively, and by 0.5, 0.5 and 0.3% in type 2 diabetes patients, respectively. Body mass index in type 1 diabetes patients increased significantly (P < 0.05), whereas that in type 2 diabetes patients did not change. Basal insulin dose decreased significantly at 3 months after switching (P < 0.05), and returned baseline dose at 12 months in type 1 diabetes and type 2 diabetes patients. The frequency of both total and nocturnal hypoglycemia decreased significantly in type 1 diabetes and type 2 diabetes patients (P < 0.05). The result of multiple regression analysis showed that baseline HbA1c was a significant independent variable of the percentage change in HbA1c with switching. CONCLUSION: In both type 1 diabetes and type 2 diabetes patients, switching from insulin glargine or insulin detemir to insulin degludec led to improvement of glycemic control with a significant reduction of hypoglycemia. PMID- 27181265 TI - Targeting multiple response regulators of Mycobacterium tuberculosis augments the host immune response to infection. AB - The genome of M. tuberculosis (Mtb) encodes eleven paired two component systems (TCSs) consisting of a sensor kinase (SK) and a response regulator (RR). The SKs sense environmental signals triggering RR-dependent gene expression pathways that enable the bacterium to adapt in the host milieu. We demonstrate that a conserved motif present in the C-terminal domain regulates the DNA binding functions of the OmpR family of Mtb RRs. Molecular docking studies against this motif helped to identify two molecules with a thiazolidine scaffold capable of targeting multiple RRs, and modulating their regulons to attenuate bacterial replication in macrophages. The changes in the bacterial transcriptome extended to an altered immune response with increased autophagy and NO production, leading to compromised survival of Mtb in macrophages. Our findings underscore the promise of targeting multiple RRs as a novel yet unexplored approach for development of new anti-mycobacterial agents particularly against drug-resistant Mtb. PMID- 27181267 TI - Simultaneous deactivation of FAK and Src improves the pathology of hypertrophic scar. AB - Hypertrophic scar (HS) is a serious fibrotic skin condition with currently no satisfactory therapy due to undefined molecular mechanism. FAK and Src are two important non-receptor tyrosine kinases that have been indicated in HS pathogenesis. Here we found both FAK and Src were activated in HS vs. normal skin (NS), NS fibroblasts treated with TGF-beta1 also exhibited FAK/Src activation. Co immunoprecipitation and dual-labelled immunofluorescence revealed an enhanced FAK Src association and co-localization in HS vs. NS. To examine effects of FAK/Src activation and their interplay on HS pathogenesis, site-directed mutagenesis followed by gene overexpression was conducted. Results showed only simultaneous overexpression of non-phosphorylatable mutant FAK Y407F and phosphomimetic mutant Src Y529E remarkably down-regulated the expression of Col I, Col III and alpha SMA in cultured HS fibroblasts, alleviated extracellular matrix deposition and made collagen fibers more orderly in HS tissue vs. the effect from single transfection with wild-type or mutational FAK/Src. Glabridin, a chemical found to block FAK-Src complex formation in cancers, exhibited therapeutic effects on HS pathology probably through co-deactivation of FAK/Src which further resulted in FAK-Src de-association. This study suggests FAK-Src complex could serve as a potential molecular target, and FAK/Src double deactivation might be a novel strategy for HS therapy. PMID- 27181268 TI - Incidence and risk of hypertension associated with cabozantinib in cancer patients: a systematic review and meta-analysis. AB - INTRODUCTION: Cabozantinib (XL184) is an oral inhibitor of multiplereceptor tyrosine kinases including mesenchymal-epithelial transition factor (MET) and vascular endothelial growth factor receptor 2 (VEGFR2). Hypertension is one of its major side effects, but the incidence rate and overall risk has not been systematically studied. We thus conducted this meta-analysis to investigate the overall incidence and risk of developing hypertension in cancer patients treated with cabozantinib. AREAS COVERED: Pubmed, Embase and oncology conference proceedings were searched for relevant studies. Eligible studies were phase II and III prospective clinical trials of cabozantinib in cancer patients with data on hypertension available. A total of 1,514 patients (cabozantinib, 1083; control, 431) with a variety of solid tumors from 8 prospective clinical trials were included for the meta-analysis. The use of cabozantinib was associated with significantly increased risk of developing all grade (RR 5.48; 95%CI, 3.76-7.99; p < 0.001) and high grade (5.09; 95% CI: 2.71-9.54, p < 0.001) hypertension in comparison with controls. Additionally, the risk of high grade hypertension with cabozantinib was substantially higher than other four approved VEGFR-TKIs (sorafenib, sunitinib, vandetanib and pazopanib). Expert commentary: Cancer patients receiving cabozantinib have an increased risk of developing hypertension. Close monitoring and management of hypertension are recommended. PMID- 27181269 TI - Changes in serum adipocyte fatty acid-binding protein in women with gestational diabetes mellitus and normal pregnant women during mid- and late pregnancy. AB - AIMS/INTRODUCTION: To observe the longitudinal changes in serum adipocyte fatty acid-binding protein (AFABP), carbohydrate, and lipid metabolism parameters in women with and without gestational diabetes mellitus (GDM) during mid- and late pregnancy periods, as well as to identify whether there is any association between AFABP and development of GDM. MATERIALS AND METHODS: A total of 40 GDM and 240 normal glucose tolerance participants were enrolled at 24-28 weeks and completed the study. The clinical features, serum AFABP, other adipocytokines (leptin, adiponectin, retinol-binding protein 4), homeostasis model assessment of insulin resistance, and lipid profiles were measured in the second and third trimesters of pregnancy. RESULTS: Compared with the normal glucose tolerance group, the GDM group showed greater levels of AFABP, leptin and retinol-binding protein 4; and a decreased level of adiponectin (P < 0.05 or P < 0.01) during mid and late pregnancy periods. Prepregnancy body mass index was the independent factor impacting serum AFABP levels in the second (beta = 0.567, P = 0.004) and third trimesters (beta = 0.619, P = 0.001). Furthermore, GDM was independently associated with AFABP concentrations in multiple regression analysis in the second and third trimester (all P < 0.01). Serum AFABP, leptin and retinol binding protein 4 are risk factors for GDM; adiponectin is a protective factor for GDM (P < 0.05 or P < 0.01). CONCLUSIONS: The GDM group had a higher level of AFABP during mid- and late stages of pregnancy; prepregnancy body mass index and GDM were the independent factors with respect to serum AFABP. AFABP might be closely related to obesity, insulin resistance and leptin resistance in pregnancy, and is a major risk factor for GDM. PMID- 27181272 TI - Polyamine-Cladded 18-Ring-Channel Gallium Phosphites with High-Capacity Hydrogen Adsorption and Carbon Dioxide Capture. AB - In this study, we synthesized a unique inorganic framework bearing the largest 18 membered-ring channels in gallium phosphites, denoted as NTHU-15, which displayed genuine porosity even though large organic templates were present. The idea of using the "template-cladded" strategy succeeded in releasing channel space of up to ~24% of the unit-cell volume as highly positive-charged organic templates were manipulated to cling to the anionic inorganic walls. NTHU-15 showed both high H2 uptake of 3.8 mmol/g at 77 K and effective CO2 adsorption of ~2.4 mmol/g at 298 K, which surpassed those of all other known extra-large-channel inorganic framework structures. NTHU-15 has been successful at overcoming the long-standing problem of organic-templated extra-large-channel structures as opposed to a "true open" framework. Moreover, it realized practical gas sorption functionality in innovated metal phosphites. In view of its high stability in hot water and high selectivity for CO2 adsorption, NTHU-15 may be the first novel inorganic framework material to be applied to the field of flue gas cleaning. PMID- 27181270 TI - Migraine: What Imaging Reveals. AB - Although migraine symptomatology is well-defined, our understanding of migraine pathophysiology is incomplete. Structural and functional brain imaging can contribute to a greater understanding of migraine pathophysiology. Recent neuroimaging studies demonstrate that migraine is associated with structural and functional alterations of brain regions commonly implicated in pain processing. This review summarizes recent brain structural and functional imaging findings in migraine and highlights those that are associated with characteristics such as the presence or absence of aura, associated cognitive dysfunction, sex differences (male vs. female migraineurs), age, and disease burden. PMID- 27181273 TI - Non-linear photoelectron effect contributes to the formation of negative matrix ions in UV-MALDI. AB - The mechanism of negative ion formation in matrix-assisted laser desorption/ionization (MALDI) is less well understood than that of positive ions: electron capture, disproportionation, and liberation of negatively charged sample molecules or clusters have been proposed to produce the initial anions in MALDI. Here, we propose that the non-linear photoelectric effect can explain the emission of electrons from the metallic target material. Moreover, electrons with sufficient kinetic energy (0-10 eV) could be responsible for the formation of initial negative ions. Gas-phase electron capture by neutral 2,5-dihydroxy benzoic acid (DHB) to yield M(-) is investigated on the basis of a coupled physical and chemical dynamics (CPCD) theory from the literature. A three-layer energy mass balance model is utilized to calculate the surface temperature of the matrix, which is used to determine the translational temperature, the number of desorbed matrix molecules per unit area, and the ion velocity. Calculations of dissociative attachment and autoionization rates of DHB are presented. It was found that both processes contribute significantly to the formation of [M - H](-) and [M - H2](-), although the predicted yield in the fluence range of 5-100 mJ cm(-2) is low, certainly less than that for positive ions M(+). This work represents the first proposal for a comprehensive theoretical description of negative ion formation in UV-MALDI. PMID- 27181271 TI - New Techniques and Progress in Epilepsy Surgery. AB - While open surgical resection for medically refractory epilepsy remains the gold standard in current neurosurgical practice, modern techniques have targeted areas for improvement over open surgical resection. This review focuses on how a variety of these new techniques are attempting to address these various limitations. Stereotactic electroencephalography offers the possibility of localizing deep epileptic foci, improving upon subdural grid placement which limits localization to neocortical regions. Laser interstitial thermal therapy (LITT) and stereotactic radiosurgery can minimally or non-invasively ablate specific regions of interest, with near real-time feedback for laser interstitial thermal therapy. Finally, neurostimulation offers the possibility of seizure reduction without needing to ablate or resect any tissue. However, because these techniques are still being evaluated in current practice, there are no evidence based guidelines for their use, and more research is required to fully evaluate their proper role in the current management of medically refractory epilepsy. PMID- 27181274 TI - Characterization of heat shock cognate protein 70 gene and its differential expression in response to thermal stress between two wing morphs of Nilaparvata lugens (Stal). AB - Previous studies have demonstrated differences in thermotolerance between two wing morphs of Nilaparvata lugens, the most serious pest of rice across the Asia. To reveal the molecular regulatory mechanisms underlying the differential thermal resistance abilities between two wing morphs, a full-length of transcript encoding heat shock cognate protein 70 (Hsc70) was cloned, and its expression patterns across temperature gradients were analyzed. The results showed that the expression levels of NlHsc70 in macropters increased dramatically after heat shock from 32 to 38 degrees C, while NlHsc70 transcripts in brachypters remained constant under different temperature stress conditions. In addition, NlHsc70 expression in the macropters was significantly higher than that in brachypters at 1 and 2h recovery from 40 degrees C heat shock. There was no significant difference in NlHsc70 mRNA expression between brachypters and macropters under cold shock conditions. Therefore, NlHsc70 was indeed a constitutively expressed member of the Hsp70 family in brachypters of N. lugens, while it was heat inducible in macropters. Furthermore, the survival rates of both morphs injected with NlHsc70 dsRNA were significantly decreased following heat shock at 40 degrees C or cold shock at 0 degrees C for 1h. These results suggested that the up-regulation of NlHsc70 is possibly related to the thermal resistance, and the more effective inducement expression of NlHsc70 in macropters promotes a greater thermal tolerance under temperature stress conditions. PMID- 27181275 TI - Evaluation of clinical implementation of prospective DPYD genotyping in 5 fluorouracil- or capecitabine-treated patients. AB - AIM: Fluoropyrimidines are commonly used anti-cancer drugs, but lead to severe toxicity in 10-30% of patients. Prospective DPYD screening identifies patients at risk for toxicity and leads to a safer treatment with fluoropyrimidines. This study evaluated the routinely application of prospective DPYD screening at the Leiden University Medical Center. METHODS: Prospective DPYD screening as part of routine patient care was evaluated by retrospectively screening databases and patient files to determine genotype, treatment, dose recommendations and dose adjustments. RESULTS: 86.9% of all patients with a first fluoropyrimidine prescription were screened. Fourteen out of 275 patients (5.1%) carried a DPYD variant and received a 25-50% dose reduction recommendation. None of the patients with a DPYD variant treated with a reduced dose developed toxicities. CONCLUSION: Prospective DPYD screening can be implemented successfully in a real world clinical setting, is well accepted by physicians and results in low toxicity. PMID- 27181276 TI - Heart rate variability and depressive symptoms: a cross-lagged analysis over a 10 year period in the Whitehall II study. AB - BACKGROUND: People with depression tend to have lower heart rate variability (HRV), but the temporal sequence is poorly understood. In a sample of the general population, we prospectively examined whether HRV measures predict subsequent depressive symptoms or whether depressive symptoms predict subsequent levels of HRV. METHOD: Data from the fifth (1997-1999) and ninth (2007-2009) phases of the UK Whitehall II longitudinal population-based cohort study were analysed with an average follow-up of 10.5 years. The sample size for the prospective analysis depended on the analysis and ranged from 2334 (644 women) to 2276 (602 women). HRV measures during 5 min of supine rest were obtained. Depressive symptoms were evaluated by four cognitive symptoms of depression from the General Health Questionnaire. RESULTS: At follow-up assessment, depressive symptoms were inversely associated with HRV measures independently of antidepressant medication use in men but not in women. Prospectively, lower baseline heart rate and higher HRV measures were associated with a lower likelihood of incident depressive symptoms at follow-up in men without depressive symptoms at baseline. Similar but statistically insignificant associations were found in women. Adjustments for known confounders including sociodemographic and lifestyle factors, cardiometabolic conditions or medication did not change the predictive effect of HRV on incident depressive symptoms at follow-up. Depressive symptoms at baseline were not associated with heart rate or HRV at follow-up in either sex. CONCLUSIONS: These findings are consistent with an aetiological role of the autonomic nervous system in depression onset. PMID- 27181277 TI - Cardiovascular autonomic neuropathy in patients with type 2 diabetes. AB - AIMS/INTRODUCTION: Heart rate recovery (HRR) after exercise is considered to be a new index of autonomic dysfunction associated with cardiovascular disease and mortality. The present study aimed to investigate the risk factors of HRR and the effects of exercise on the abnormal HRR in type 2 diabetes. MATERIALS AND METHODS: A total of 123 type 2 diabetes patients were recruited, and the oral glucose tolerance test and exercise test were carried out to analyze the risk factors associated with abnormal HRR. Among these patients, 42 patients with abnormal HRR were further randomized to either the conventional therapy group (CT group; n = 20) or the intensive therapy group (IT group; n = 22). The CT group patients underwent metformin and diet control, whereas the IT group additionally underwent a combined moderate intensity aerobic and resistance training three times per week for 12 weeks. The results of blood sample analysis and HRR were recorded before and after the training. RESULTS: Abnormal HRR was related to fasting blood glucose, glycosylated hemoglobin, low-density lipoprotein cholesterol, and resting and maximum heart rates (P < 0.05 for both). After training, the IT group had significantly lower levels of fasting blood glucose, glycosylated hemoglobin and resting heart rate than the CT group (all P < 0.01 or P < 0.005). Significant improvement in HRR and metabolic equivalents was observed in the IT group compared with the CT group (P < 0.05). CONCLUSIONS: These data suggested that combined aerobic and resistance training improved cardiac autonomic dysfunction as measured by HRR in type 2 diabetes patients. This might be due to better improvement of glycemic control, resting heart rate and physical fitness. PMID- 27181278 TI - Virus-Templated Near-Amorphous Iron Oxide Nanotubes. AB - We present a simple synthesis of iron oxide nanotubes, grown under very mild conditions from a solution containing Fe(II) and Fe(III), on rod-shaped tobacco mosaic virus templates. Their well-defined shape and surface chemistry suggest that these robust bionanoparticles are a versatile platform for synthesis of small, thin mineral tubes, which was achieved efficiently. Various characterization tools were used to explore the iron oxide in detail: Electron microscopy (SEM, TEM), magnetometry (SQUID-VSM), diffraction (XRD, TEM-SAED), electron spectroscopies (EELS, EDX, XPS), and X-ray absorption (XANES with EXAFS analysis). They allowed determination of the structure, crystallinity, magnetic properties, and composition of the tubes. The protein surface of the viral templates was crucial to nucleate iron oxide, exhibiting analogies to biomineralization in natural compartments such as ferritin cages. PMID- 27181279 TI - Aluminium salabza complexes for fixation of CO2 to organic carbonates. AB - A highly stable and easy to synthesize aluminium complex bearing a flexible N2O2 donor salabza ligand (N,N'-bis(salicylene)-2-aminobenzylamine) in combination with tetrabutylammonium bromide forms an active binary catalytic system for the cycloaddition of CO2 to epoxides (TOFs 120-3434 h(-1)) under mild conditions (10 bar, 80 degrees C) and low catalyst loadings (0.05-0.2 mol%). Kinetic experiments have shown that the cycloaddition of CO2 to styrene oxide catalyzed by 1/TBAB is first order in 1, TBAB, CO2 and epoxide. A reaction mechanism is proposed based on these observations. Fe(iii) and Co(iii) related complexes are less active catalysts for this reaction. PMID- 27181285 TI - Solar Photochemical Synthesis: From the Beginnings of Organic Photochemistry to the Solar Manufacturing of Commodity Chemicals. AB - Natural sunlight offers a cost-efficient and sustainable energy source for photochemical reactions. In contrast to the lengthy and small-scale "flask in the sun" procedures of the past, modern solar concentrator systems nowadays significantly shorten reaction times and enable technical-scale operations. After a brief historical introduction, this review presents the most important solar reactor types and their successful application in preparative solar syntheses. The examples demonstrate that solar manufacturing of fine chemicals is technically feasible and environmentally sustainable. After over 100 years, Ciamician's prophetic vision of "the photochemistry of the future" as a clean and green manufacturing methodology has yet to be realized. At the same time, his warning "for nature is not in a hurry but mankind is" is still valid today. It is hoped that this review will lead to a renewed interest in this truly enlightening technology, that it will stimulate photochemists and photochemical engineers to "go back to the roots onto the roofs" and that it will ultimately result in industrial applications in the foreseeable future. PMID- 27181284 TI - Experience with S-1 in older Caucasian patients with metastatic colorectal cancer (mCRC): Findings from an observational chart review. AB - BACKGROUND: An aging population will increase the number of older patients with metastatic colorectal cancer (mCRC). However, there is limited knowledge about treatment in older patients as they are under-represented in clinical trials. The oral fluoropyrimidine S-1 is associated with a lower rate of adverse events than capecitabine and may therefore be a suitable drug for elderly. However, data on the use of S-1 in Caucasian mCRC patients are lacking/scarce. MATERIAL AND METHODS: In the present study we evaluated safety and the efficacy of S-1 alone or in combination with oxaliplatin (SOx) or irinotecan (IRIS) in older mCRC patients. Patients who received at least one cycle of S-1 (first-line therapy), SOx (mainly first-line therapy) or IRIS (second-line therapy) were included. RESULTS: From June 2012 to December 2014, 71 older patients received >=1 cycle of either S-1 (n = 9), SOx (n = 44) or IRIS (n = 18) for mCRC. Median age was 76 years and most patients had a WHO performance status of 0 (32%) or 1 (56%). All patients were evaluable for response and safety. In the SOx group, 18 (41%) and 20 patients (45%) had partial response (PR) and stable disease (SD), respectively (disease control rate 86%). Median progression-free survival (PFS) was 8.5 months and median overall survival (OS) was 18.5 months. In the S-1 group (median age 82 years), PR was 22%, median PFS 6.4 months and median OS 15.8 months. In the IRIS group, PR was 28%, median PFS 7.8 months and the median OS 16.5 months. In general, therapy was well tolerated; main non-hematological toxicities were fatigue and diarrhea. CONCLUSION: S-1 monotherapy, SOx and IRIS were well tolerated for older patients with mCRC and could become alternative regimens in older mCRC patients. These regimens are now further evaluated in the randomized ongoing NORDIC9 trial. PMID- 27181286 TI - The value of magnetic resonance cholangiopancreatography for the exclusion of choledocholithiasis. AB - OBJECTIVE: To investigate the ability of Magnetic resonance cholangiopancreatography (MRCP) to exclude choledocholithiasis (CDL) in symptomatic patients. MATERIAL AND METHODS: Patients suspected of choledocholithiasis who underwent MRCP from 2008 through 2013 in a population based study at the National University Hospital of Iceland were retrospectively analysed, using ERCP and/or intraoperative cholangiography as a gold standard diagnosis for CDL. RESULTS: Overall 920 patients [66% women, mean age 55 years (SD 21)] underwent MRCP. A total of 392 patients had a normal MRCP of which 71 underwent an ERCP investigation demonstrating a CBD stone in 29 patients. A normal MRCP was found to have a 93% negative predictive value (NPV) and 89% probability of having no CBD stone demonstrated as well as no readmission due to gallstone disease within six months following MRCP. During a 6-month follow-up period of the 321 patients who did not undergo an ERCP nine (2.8%) patients were readmitted with right upper quadrant pain and elevated liver tests which later normalised with no CBD stone being demonstrated, three (0.9%) patients were readmitted with presumed gallstone pancreatitis, two (0.6%) patients were readmitted with cholecystitis and two (0.6%) patients were lost to follow-up. Seven patients of those 321 underwent an intraoperative cholangiography (IOC) and all were negative for CBD stones. For the sub-group requiring ERCP following a normal MRCP the NPV was 63%. CONCLUSION: Our results support the use of MRCP as a tool for exclusion of choledocholithiasis with the potential to reduce the amount of unnecessary ERCP procedures. PMID- 27181287 TI - The Interplay of Shape and Crystalline Anisotropies in Plasmonic Semiconductor Nanocrystals. AB - Doped semiconductor nanocrystals are an emerging class of materials hosting localized surface plasmon resonance (LSPR) over a wide optical range. Studies so far have focused on tuning LSPR frequency by controlling the dopant and carrier concentrations in diverse semiconductor materials. However, the influence of anisotropic nanocrystal shape and of intrinsic crystal structure on LSPR remain poorly explored. Here, we illustrate how these two factors collaborate to determine LSPR characteristics in hexagonal cesium-doped tungsten oxide nanocrystals. The effect of shape anisotropy is systematically analyzed via synthetic control of nanocrystal aspect ratio (AR), from disks to nanorods. We demonstrate the dominant influence of crystalline anisotropy, which uniquely causes strong LSPR band-splitting into two distinct peaks with comparable intensities. Modeling typically used to rationalize particle shape effects is refined by taking into account the anisotropic dielectric function due to crystalline anisotropy, thus fully accounting for the AR-dependent evolution of multiband LSPR spectra. This new insight into LSPR of semiconductor nanocrystals provides a novel strategy for an exquisite tuning of LSPR line shape. PMID- 27181288 TI - Translocation dynamics of knotted polymers under a constant or periodic external field. AB - We perform Brownian dynamics simulations to examine how knots alter the dynamics of polymers moving through nanopores under an external field. In the first part of this paper, we study the situation when the field is constant. Here, knots halt translocation above a critical force with jamming occurring at smaller forces for twist topologies compared to non-twist topologies. Slightly below the jamming transition, the polymer's transit times exhibit large fluctuations. This phenomenon is an example of the knot's molecular individualism since the conformation of the knot plays a large role in the chain's subsequent dynamics. In the second part of the paper, we study the motion of the chain when one cycles the field on and off. If the off time is comparable to the knot's relaxation time, one can adjust the swelling of the knot at the pore and hence design strategies to ratchet the polymer in a controllable fashion. We examine how the off time affects the ratcheting dynamics. We also examine how this strategy alters the fluctuations in the polymer's transit time. We find that cycling the force field can reduce fluctuations near the knot's jamming transition, but can enhance the fluctuations at very high forces since knots get trapped in metastable states during the relaxation process. The latter effect appears to be more prominent for non-torus topologies than torus ones. We conclude by discussing the feasibility of this approach to control polymer motion in biotechnology applications such as sequencing. PMID- 27181290 TI - Cardiac imaging: From fetus to adult. PMID- 27181289 TI - Glycan heterogeneity on gold nanoparticles increases lectin discrimination capacity in label-free multiplexed bioassays. AB - The development of new analytical tools as point-of-care biosensors is crucial to combat the spread of infectious diseases, especially in the context of drug resistant organisms, or to detect biological warfare agents. Glycan/lectin interactions drive a wide range of recognition and signal transduction processes within nature and are often the first site of adhesion/recognition during infection making them appealing targets for biosensors. Glycosylated gold nanoparticles have been developed that change colour from red to blue upon interaction with carbohydrate-binding proteins and may find use as biosensors, but are limited by the inherent promiscuity of some of these interactions. Here we mimic the natural heterogeneity of cell-surface glycans by displaying mixed monolayers of glycans on the surface of gold nanoparticles. These are then used in a multiplexed, label-free bioassay to create 'barcodes' which describe the lectin based on its binding profile. The increased information content encoded by using complex mixtures of a few sugars, rather than increased numbers of different sugars makes this approach both scalable and accessible. These nanoparticles show increased lectin identification power at a range of lectin concentrations, relative to single-channel sensors. It was also found that some information about the concentration of the lectins can be extracted, all from just a simple colour change, taking this technology closer to being a realistic biosensor. PMID- 27181291 TI - Lower percentage of CD8+ T cells in peripheral blood of patients with sporotrichosis. AB - PURPOSE: To characterize the peripheral immunity and immunity response of patients with sporotrichosis, in this study we determined the lymphocyte subsets in the peripheral blood of Chinese patients with sporotrichosis. METHODS: In this retrospective study, peripheral blood was collected from 69 sporotrichosis patients (37, fixed cutaneous form; 32 lymphocutaneous) and 66 healthy controls. Lymphocyte subsets were analyzed using flow cytometry. RESULTS: Compared to controls, the percentage of CD8+ T cells was lower in sporotrichosis patients. The percentage of CD8+ T cells in peripheral blood tended to become lower with disease duration and disease severity, although the difference was not statistically significant for either acute, subacute and chronic patients or fixed cutaneous and lymphocutaneous patients. CONCLUSION: Our data indicate that the decrease of CD8+ T cells in peripheral blood of patients with sporotrichosis is associated with disease severity, although the difference was not statistically significant for either duration or clinical forms of the disease. Combining antifungal agents and immunomodulators in patients with long disease duration and lymphocutaneous may be more beneficial than antifungal monotherapy. PMID- 27181292 TI - Manipulating vibratory devices' orientation and position enhances proprioceptive disturbance during upright stance. AB - We tested local vibration effects during upright standing considering: (i) the orientation of vibratory devices in relation to muscle fibres; (ii) the muscle region stimulated; and (iii) the number of stimulation spots. Results showed a higher balance disturbance with vibration devices oriented parallel to triceps surae muscle fibres. The single stimulation of the proximal region of the tibialis anterior muscle belly induces the same proprioceptive disturbance as stimulating multiple regions simultaneously. PMID- 27181293 TI - Renal-Replacement Therapy in the Critically Ill--Does Timing Matter? PMID- 27181294 TI - Highly efficient shrinkage of inverted-pyramid silicon nanopores by plasma enhanced chemical vapor deposition technology. AB - Solid-state nanopore-based analysis systems are currently one of the most attractive and promising platforms in sensing fields. This work presents a highly efficient method to shrink inverted-pyramid silicon nanopores using plasma enhanced chemical vapor deposition (PECVD) technology by the deposition of SiN x onto the surface of the nanopore. The contraction of the inverted-pyramid silicon nanopores when subjected to the PECVD process has been modeled and carefully analyzed, and the modeling data are in good agreement with the experimental results within a specific PECVD shrinkage period (~0-600 s). Silicon nanopores within a 50-400 nm size range contract to sub-10 nm dimensions. Additionally, the inner structure of the nanopores after the PECVD process has been analyzed by focused ion beam cutting process. The results show an inner structure morphology change from inverted-pyramid to hourglass, which may enhance the spatial resolution of sensing devices. PMID- 27181295 TI - Goals and hurdles for a successful implementation of genomic selection in breeding programme for selected annual and perennial crops. AB - Genomic Selection is an important topic in quantitative genetics and breeding. Not only does it allow the full use of current molecular genetic technologies, it stimulates also the development of new methods and models. Genomic selection, if fully implemented in commercial farming, should have a major impact on the productivity of various agricultural systems. But suggested approaches need to be applicable in commercial breeding populations. Many of the published research studies focus on methodologies. We conclude from the reviewed publications, that a stronger focus on strategies for the implementation of genomic selection in advanced breeding lines, introduction of new varieties, hybrids or multi-line crosses is needed. Efforts to find solutions for a better prediction and integration of environmental influences need to continue within applied breeding schemes. Goals of the implementation of genomic selection into crop breeding should be carefully defined and crop breeders in the private sector will play a substantial part in the decision-making process. However, the lack of published results from studies within, or in collaboration with, private companies diminishes the knowledge on the status of genomic selection within applied breeding programmes. Studies on the implementation of genomic selection in plant breeding need to evaluate models and methods with an enhanced emphasis on population-specific requirements and production environments. Adaptation of methods to breeding schemes or changes to breeding programmes for a better integration of genomic selection strategies are needed across species. More openness with a continuous exchange will contribute to successes. PMID- 27181296 TI - Design and synthesis of unsymmetric macrocyclic hexaoxazole compounds with an ability to induce distinct G-quadruplex topologies in telomeric DNA. AB - New macrocyclic hexaoxazole compounds bearing two side chains on an unsymmetrical macrocyclic ring system, i.e., 4,2-L2H2-6OTD (2) and 5,1-L2H2-6OTD (3), were designed as candidate G-quadruplex (G4) ligands and synthesized. These G4 ligands 2 and 3 induced an anti-parallel topology and a hybrid-type topology of telomeric DNA, respectively, in contrast to the previously reported symmetrical macrocycle 3,3-L2H2-6OTD (1), which induces a typical anti-parallel structure. Molecular mechanics calculations and docking studies indicate that these differences arise from the different directions of the side chains in these L2H2-6OTD derivatives, and provide an explanation for the weaker stabilization of telomeric DNA by 2 and 3, compared with 1. PMID- 27181297 TI - Efficacy and safety of low-molecular-weight heparin in patients with sepsis: a meta-analysis of randomized controlled trials. AB - Low-molecular-weight heparin (LMWH) is part of standard supportive care. We conducted a meta-analysis to investigate the efficacy and safety of LMWH in septic patients. We searched Pubmed, Embase, CKNI and Wanfang database prior to July 2015 for randomized controlled trials investigating treatment with LMWH in septic patients. We identified 11 trials involving 594 septic patients. Meta analysis showed that LMWH significantly reduced prothrombin time (mean differences [MD] -0.88; 95% CI -1.47 to -0.29), APACHE II score (MD -2.50; 95% CI -3.55 to -1.46), and 28-day mortality (risk ratio [RR] 0.72; 95% CI 0.57-0.91) as well as increased the platelet counts (MD 18.33; 95% CI 0.73-35.93) than the usual treatment. However, LMWH did not reduce D-dimer (MD -0.34; 95% CI -0.85 to 0.18). LMWH also significantly increased the bleeding events (RR 3.82; 95% CI 1.81-8.08). LMWH appears to reduce 28-day mortality and APACHE II score among septic patients. Bleeding complications should be monitored during the LMWH treatment. As for limited data about LMWH and sepsis in the English literature, only trials published in the Chinese were included in the meta-analysis. PMID- 27181298 TI - Nine-month-olds use frequency of onset clusters to segment novel words. AB - Before their first birthday, infants have started to identify and use information about their native language, such as frequent words, transitional probabilities, and co-occurrence of segments (phonotactics), to identify viable word boundaries. These cues can then be used to segment new words from running speech. We explored whether infants are capable of detecting a novel word form using the frequency of occurrence of the onset alone to further characterize the role of phonotactics in speech segmentation. Experiment 1 shows that English-learning 9-month-olds can successfully segment a word from natural speech if the onset is legal in English (i.e., pleet) but not if the onset is illegal (i.e., tleet). Experiment 2 shows that English-learning 9-month-olds are successful at word segmentation when presented with two onset clusters that vary in statistical frequency. Infants familiarized to a high-frequency onset (i.e., trom) were successful at segmenting the target word embedded in speech, but those familiarized to the low-frequency onset (i.e., drom) were unsuccessful. Together, these results show that infants use statistical information from the speech input and that low levels of exposure to onset phonotactics alone might not be sufficient in identifying word boundaries. PMID- 27181327 TI - Are the oxygen uptake and heart rate off-kinetics influenced by the intensity of prior exercise? AB - The aim of this study was to investigate the effect of prior exercise on the heart rate (HR) and oxygen uptake (VO2) off-kinetics after a subsequent high intensity running exercise. Thirteen male futsal players (age 22.8+/-6.1years) performed a series of high-intensity bouts without prior exercise (control), preceded by a prior same intensity continuous exercise (CE+CE) and a prior sprint exercise (SE+CE). The magnitude of excess post-exercise oxygen consumption (EPOCm 4.25+/-0.19 vs. 3.69+/-0.20Lmin(-1) in CE+CE and 3.62+/-0.18Lmin(-1) in control; p<0.05) and the parasympathetic reactivation (HRR60s-33+/-3 vs. 37+/-3bpm in CE+CE and 42+/-3 bpm in control; p<0.05) in the SE+CE were higher and slower, compared with another two conditions. The EPOCtau (time to attain 63% of total response; 53+/-2s) and the heart rate time-course (HRtau-86+/-5s) were significantly longer after the SE+CE condition than control transition (48+/-2s and 69+/-5s, respectively; p<0.05). The SE+CE induce greater stress on the metabolic function, respiratory system and autonomic nervous system regulation during post-exercise recovery than CE, highlighting that the inclusion of sprint based exercises can be an effective strategy to increase the total energy expenditure following an exercise session. PMID- 27181328 TI - Maximal inspiratory pressure is influenced by intensity of the warm-up protocol. AB - The aim of the study was to compare the effect of inspiratory muscle warm-up protocols with different intensities and breathing repetitions on maximal inspiratory pressure (MIP). Ten healthy and recreationally active men (183.3+/ 5.5cm, 83.7+/-7.8kg, 26.4+/-4.1years) completed four different inspiratory muscle (IM) warm-up protocols (2*30 inspirations at 40% MIP, 2*12 inspirations at 60% MIP, 2*6 inspirations at 80% MIP, 2*30 inspirations at 15% MIP) on separate, randomly assigned visits. Pre-post values of MIP using MicroRPM (Micro Medical, Kent, UK) showed a significant increase in the mean values after the IM warm-up (POWERbreathe((r)) K1, Warwickshire, UK) with 40% MIP and 60% MIP warm-up protocols, when MIP increased by 7cm H2O (95% CI: 0.10...13.89) (p=0.047) and by 6.4cm H2O (95% CI: 2.98...13.83) (p=0.027), respectively. In conclusion, a higher intensity inspiratory muscle warm-up protocol (2*12 breaths at 60% of MIP) can increase IM strength. PMID- 27181329 TI - The hypometabolic response to repeated or prolonged hypoxic episodes in the chicken embryo. AB - Hypoxia (hx) in embryos causes a drop in oxygen consumption ( [Formula: see text] ) that rapidly recovers upon return to normoxia. We asked whether or not this pattern varies with the embryo's hypoxic history. The [Formula: see text] of chicken embryos in the middle (E12) or at end-incubation (E19) was measured by an open-flow methodology during 15-min epochs of moderate (15% O2) or severe hx (10% O2). Each hx-epoch was repeated or alternated with air by various modalities (air hx-air-hx-air-hx-air, air-2.hx-air-2.hx-air, air-5.hx-air), in randomized sequences. The hx drop in [Formula: see text] was larger with severe than with moderate hx; however, in either case, its magnitude was essentially independent of the preceding hx history. E19 embryos had hx drops in [Formula: see text] of the same magnitude whether their incubation was in air or in moderate hx from E4 to E19. A different protocol (air-12.hx-air) gave variable results; with moderate hx, the [Formula: see text] response was similar to that of the other hx regimes. Differently, with severe hx most embryos progressively decreased [Formula: see text] and eventually died. We interpret these data on the basis of what is known on the 'compensatory partitioning' between costs of growth and maintenance. With moderate hx presumably each episode caused an energy shortfall absorbed entirely by the blunted growth. Hypoxic events of this type, therefore, should have no long-term functional effects other than those related to the small birth weight. Differently, the aerobic energy shortfall with severe hypoxia probably impinged on some maintenance functions and became incompatible with survival. PMID- 27181326 TI - Interleukin-1beta and interleukin-6 enhance thermal prolongation of the LCR in decerebrate piglets. AB - Thermal stress and prior upper respiratory tract infection are risk factors for the Sudden Infant Death Syndrome. The adverse effects of prior infection are likely mediated by interleukin-1beta (IL-1beta). Therefore, we examined the single and combined effects of IL-1beta and elevated body temperature on the duration of the Laryngeal Chemoreflex (LCR) in decerebrate neonatal piglets ranging in age from post-natal day (P) 3 to P7. We examined the effects of intraperitoneal (I.P.) injections of 0.3mg/Kg IL-1beta with or without I.P. 10mg/Kg indomethacin pretreatment on the duration of the LCR, and in the same animals we also examined the duration of the LCR when body temperature was elevated approximately 2 degrees C. We found that IL-1beta significantly increased the duration of the LCR even when body temperature was held constant. There was a significant multiplicative effect when elevated body temperature was combined with IL-1beta treatment: prolongation of the LCR was significantly greater than the sum of independent thermal and IL-1beta-induced prolongations of the LCR. The effects of IL-1beta, but not elevated body temperature, were blocked by pretreatment with indomethacin alone. We also tested the interaction between IL-6 given directly into the nucleus of the solitary tract (NTS) bilaterally in 100ngm microinjections of 50MUL and pretreatment with indomethacin. Here again, there was a multiplicative effect of IL-6 treatment and elevated body temperature, which significantly prolonged the LCR. The effect of IL-6 on the LCR, but not elevated body temperature, was blocked by pretreatment with indomethacin. We conclude that cytokines interact with elevated body temperature, probably through direct thermal effects on TRPV1 receptors expressed pre synaptically in the NTS and through cytokine-dependent sensitization of the TRPV1 receptor. This sensitization is likely initiated by cyclo-oxygenase-2 dependent synthesis of prostaglandin E2, which is stimulated by elevated levels of IL-1beta or IL-6. Inflammatory sensitization of the LCR coupled with thermal prolongation of the LCR may increase the propensity for apnea and Sudden Infant Death Syndrome. PMID- 27181330 TI - Maximal inspiratory mouth pressure in Japanese elite male athletes. AB - Maximal inspiratory mouth pressure (MIP) is a common measurement of inspiratory muscle strength, which is often used in a variety of exercises to evaluate the effects of inspiratory muscle training. An understanding of elite athletes' MIP characteristics is needed to guide sport-specific inspiratory muscle training programs. The purpose of this study was to investigate and better understand the MIP characteristics of elite athletes from a variety of sports. A total of 301 Japanese elite male athletes participated in this study. MIP was assessed using a portable autospirometer with a handheld mouth pressure meter. Athletes with higher body mass tended to have stronger MIP values, in absolute terms. In relative terms, however, athletes who regularly experienced exercise-induced inspiratory muscle fatigue tended to have stronger MIP values. Our findings suggest that athletes could benefit from prescribed, sport-specific, inspiratory muscle training or warm-ups. PMID- 27181331 TI - Preiser's disease in a five-fingered hand. AB - Preiser's disease, also known as idiopathic avascular necrosis of the scaphoid, and five-fingered hand are rare hand conditions. In this report, we present a case of a 25 year old female patient who had avascular necrosis of the scaphoid and five-fingered hand. PMID- 27181333 TI - Production of biologically active oxidized derivatives of finasteride through metabolism by Aspergillus niger culture. AB - CONTEXT: Among the 4-azasteroids, finasteride is biologically the most important compound having preventive effect against male pattern baldness (MPH) and benign prostatic hyperplasia commonly called enlargement of prostate gland. OBJECTIVE: The microbial transformation of finasteride by fungus Aspergillus niger (ATCC 10549) has been investigated to obtain biologically more potent derivatives. MATERIALS AND METHODS: Fermentation of finasteride was performed with filamentous fungus Aspergillus niger (ATCC 10549). This transformation resulted in the production of two transformed products, which were purified through column chromatography. In vitro lipoxygenase inhibitory potential was determined by incubating 20 mL of the enzyme with 10 mL of test sample (100 MUM) in 0.1 mM (pH 7.0) phosphate buffer for 5 min at 258 degrees C followed by addition of 10 MUL of substrate (linolenic acid) to reaction mixture and measuring the formation of complex spectrophotometrically. RESULTS: Structure elucidation of biotransformed metabolites was ascertained through extensive 1D and 2D spectroscopic techniques. This study established the fact that A. niger promoted stereospecific dihydroxylation at C-11 and C-15 of finasteride. The resulting biotransformed metabolites were characterized as 11alpha-hydroxyfinasteride and 15beta hydroxyfinasteride, respectively. Finasteride along with transformed metabolites were analyzed for their in vitro lipoxygenase (LOX) inhibition assay. Among the tested compounds 15beta-hydroxyfinasteride showed good activity with IC50 value 112.56 +/- 2.23 MUM while inhibitory effect in case of 11alpha-hydroxyfinasteride was low with IC50 value 186.05 +/- 1.34 MUM. Standard compound baicalein revealed IC50 value being 22.0 +/- 0.05 MUM. CONCLUSION: The present investigation highlighted the fact that potentially active compound can be produced through the technology of biotransformation. PMID- 27181332 TI - BCR-ABL-specific CD4+ T-helper cells promote the priming of antigen-specific cytotoxic T cells via dendritic cells. AB - The advent of tyrosine kinase inhibitor (TKI) therapy markedly improved the outcome of patients with chronic-phase chronic myeloid leukemia (CML). However, the poor prognosis of patients with advanced-phase CML and the lifelong dependency on TKIs are remaining challenges; therefore, an effective therapeutic has been sought. The BCR-ABL p210 fusion protein's junction region represents a leukemia-specific neoantigen and is thus an attractive target for antigen specific T-cell immunotherapy. BCR-ABL p210 fusion-region-specific CD4+ T-helper (Th) cells possess antileukemic potential, but their function remains unclear. In this study, we established a BCR-ABL p210 b3a2 fusion-region-specific CD4+ Th cell clone (b3a2-specific Th clone) and examined its dendritic cell (DC)-mediated antileukemic potential. The b3a2-specific Th clone recognized the b3a2 peptide in the context of HLA-DRB1*09:01 and exhibited a Th1 profile. Activation of this clone through T-cell antigen receptor stimulation triggered DC maturation, as indicated by upregulated production of CD86 and IL-12p70 by DCs, which depended on CD40 ligation by CD40L expressed on b3a2-specific Th cells. Moreover, in the presence of HLA-A*24:02-restricted Wilms tumor 1 (WT1)235-243 peptide, DCs conditioned by b3a2-specific Th cells efficiently stimulated the primary expansion of WTI-specific cytotoxic T lymphocytes (CTLs). The expanded CTLs were cytotoxic toward WT1235-243-peptide-loaded HLA-A*24:02-positive cell lines and exerted a potent antileukemic effect in vivo. However, the b3a2-specific Th-clone mediated antileukemic CTL responses were strongly inhibited by both TKIs and interferon-alpha. Our findings indicate a crucial role of b3a2-specific Th cells in leukemia antigen-specific CTL-mediated immunity and provide an experimental basis for establishing novel CML immunotherapies. PMID- 27181334 TI - Marijuana: The Societal and Health Paradox. PMID- 27181336 TI - Significant curvature effects of partially charged carbon nanotubes on electrolyte behavior investigated using Monte Carlo simulations. AB - Carbon nanotubes and graphene are among the major nanomaterials in nanoscience and technology. Despite having pi electrons, these nanocarbon allotropes have been simply considered as neutral in classical calculations. In this study, the effects of partial charges on graphene and curved interfaces on molecular adsorption were investigated using Monte Carlo simulations of N2 and NaCl aqueous solutions on graphene and carbon nanotubes. The simulated N2 adsorption behavior and adsorption potential on partially charged and non-charged graphene coincided with each other. The adsorption potentials suggested that partially charged graphene attracted Na ions and repelled Cl ions. However, those tendencies were not present in NaCl aqueous solutions on graphene. Conversely, in partially charged carbon nanotube models, a preference for Na ions and repulsion of Cl ions in the internal nanospaces were observed in the adsorption potentials using Monte Carlo simulations. Curved interfaces in the internal nanospaces of carbon nanotubes enhanced these properties, suggesting significant electrostatic interactions in a curved pi-conjugated system. PMID- 27181335 TI - Effect of alpha-linolenic acid and DHA intake on lipogenesis and gene expression involved in fatty acid metabolism in growing-finishing pigs. AB - The regulation of lipogenesis mechanisms related to consumption of n-3 PUFA is poorly understood. The aim of the present study was to find out whether alpha linolenic acid (ALA) or DHA uptake can have an effect on activities and gene expressions of enzymes involved in lipid metabolism in the liver, subcutaneous adipose tissue and longissimus dorsi (LD) muscle of growing-finishing pigs. Six groups of ten pigs received one of six experimental diets supplemented with rapeseed oil in the control diet, extruded linseed, microalgae or a mixture of both to implement different levels of ALA and DHA with the same content in total n-3. Results were analysed for linear and quadratic effects of DHA intake. The results showed that activities of malic enzyme (ME) and fatty acid synthase (FAS) decreased linearly in the liver with dietary DHA. Although the expression of the genes of these enzymes and their activities were poorly correlated, ME and FAS expressions also decreased linearly with DHA intake. The intake of DHA down regulates the expressions of other genes involved in fatty acid (FA) metabolism in some tissues of pigs, such as fatty acid desaturase 2 and sterol-regulatory element binding transcription factor 1 in the liver and 2,4-dienoyl CoA reductase 2 in the LD muscle. FA oxidation in the LD muscle and FA synthesis decreased in the liver with increasing amount of dietary DHA, whereas a retroconversion of DHA into EPA seems to be set up in this last tissue. PMID- 27181337 TI - Plasmon-enhanced Electrically Light-emitting from ZnO Nanorod Arrays/p-GaN Heterostructure Devices. AB - Effective and bright light-emitting-diodes (LEDs) have attracted broad interests in fundamental research and industrial application, especially on short wavelength LEDs. In this paper, a well aligned ZnO nanorod arrays grown on the p GaN substrate to form a heterostructured light-emitting diode and Al nanoparticles (NPs) were decorated to improve the electroluminescence performance. More than 30-folds enhancement of the electroluminescence intensity was obtained compared with the device without Al NPs decoration. The investigation on the stable and transient photoluminescence spectraof the ZnO nanorod arrays before and after Al NPs decoration demonstrated that the metal surface plasmon resonance coupling with excitons of ZnO leads to the enhancement of the internal quantum efficiency (IQE). Our results provide aneffective approach to design novel optoelectronic devices such as light-emitting diodes and plasmonic nanolasers. PMID- 27181338 TI - Reversible regulation of the supramolecular chirality of a cyanine dye by using the G-quadruplex structure as a template. AB - Multiple cycle regulation of the supramolecular chirality of a cyanine dye has been successfully achieved by using DNA G-quadruplexes as templates, which is easily controllable by repeated addition of Ag(+) and cysteine (Cys). This work provides an easy and controllable strategy for the chiral regulation of supramolecules. PMID- 27181340 TI - Improving the hydrogen selectivity of graphene oxide membranes by reducing non selective pores with intergrown ZIF-8 crystals. AB - We report the intergrowth of ZIF-8 crystals on ultrathin graphene oxide (GO) membranes, which helps to reduce the non-selective pores of pristine GO membranes leading to gas selectivities as high as 406, 155, and 335 for H2/CO2, H2/N2, and H2/CH4 mixtures, respectively. PMID- 27181341 TI - Behavior change stages related to physical activity in adolescents from Santa Catarina: prevalence and associated factors. AB - OBJECTIVE: Verify the prevalence and sociodemographic and economic factors associated with behavior change stages for habitual physical activity practice in adolescents from Santa Catarina. METHODS: Secondary analysis of a study on the Behavior of Adolescents from Santa Catarina (CompAC 2). Cross-sectional school based study of 6,529 high-school students (males, n=2,903) from the state of Santa Catarina public education system in 2011, aged 15 to 19 years. Multinomial logistic regression (crude and adjusted) was used to measure the association. RESULTS: The highest and lowest prevalence rates were found in the maintenance (43.9%) and precontemplation stages (7.0%), respectively. The stages of action, preparation and contemplation showed similar results: 16.2%; 17.0% and 15.6%; respectively. Male adolescents show higher prevalence in the maintenance stage in relation to females and these show a higher prevalence in preparation, contemplation and precontemplation. All the assessed variables (gender, age, area of residence, employment status, family income, maternal education and school grade), with the exception of school shift, were associated with at least one of the stages. CONCLUSIONS: A large proportion of adolescents are in the pre adoption stages and most of these have the intention to start regular physical activity. With the exception of school shift, the assessed variables were associated with stages in different ways, showing different profiles in relation to sociodemographic and economic characteristics in each subgroup. PMID- 27181339 TI - Reduced cerebral blood flow and oxygen metabolism in extremely preterm neonates with low-grade germinal matrix- intraventricular hemorrhage. AB - Low-grade germinal matrix-intraventricular hemorrhage (GM-IVH) is the most common complication in extremely premature neonates. The occurrence of GM-IVH is highly associated with hemodynamic instability in the premature brain, yet the long-term impact of low-grade GM-IVH on cerebral blood flow and neuronal health have not been fully investigated. We used an innovative combination of frequency-domain near infrared spectroscopy and diffuse correlation spectroscopy (FDNIRS-DCS) to measure cerebral oxygen saturation (SO2) and an index of cerebral blood flow (CBFi) at the infant's bedside and compute an index of cerebral oxygen metabolism (CMRO2i). We enrolled twenty extremely low gestational age (ELGA) neonates (seven with low-grade GM-IVH) and monitored them weekly until they reached full-term equivalent age. During their hospital stay, we observed consistently lower CBFi and CMRO2i in ELGA neonates with low-grade GM-IVH compared to neonates without hemorrhages. Furthermore, lower CBFi and CMRO2i in the former group persists even after the resolution of the hemorrhage. In contrast, SO2 does not differ between groups. Thus, CBFi and CMRO2i may have better sensitivity than SO2 in detecting GM-IVH-related effects on infant brain development. FDNIRS-DCS methods may have clinical benefit for monitoring the evolution of GM-IVH, evaluating treatment response, and potentially predicting neurodevelopmental outcome. PMID- 27181342 TI - Use of honey associated with Ananas comosus (Bromelin) in the treatment of acute irritative cough. AB - OBJECTIVE: To evaluate the immediate improvement rate of irritative cough in patients treated with the combination of Ananas comosus extract and honey (Bromelin(r)) compared with the use of honey alone (placebo group). METHODS: Pragmatic, double-blind, randomized, parallel-group study with children aged between 2 and 15 years, with irritative cough for at least 24hours. The double blind assessment of cough was through the number of observed coughing episodes and intensity score for a period of 10minutes of observation. The decrease of one point in the mean total score was considered as a therapeutic effect. RESULTS: There was a reduction in coughing episodes in both groups, as well as in the cough score after 30minutes of drug or honey administration. The change in clinical score above two points, which could indicate marked improvement, occurred in five patients in the bromelin group and only in one in the placebo group, but without significant difference. There were no adverse events. CONCLUSIONS: The immediate improvement rate of irritative cough was similar in patients treated with combination of Ananas comosus extract and honey (Bromelin(r)) compared with the use of honey alone (placebo group). It is possible that honey has a therapeutic effect on mucus and cough characteristics (Clinical Trials: NCT01356693). PMID- 27181343 TI - Association of growth and nutritional parameters with pulmonary function in cystic fibrosis: a literature review. AB - OBJECTIVE: To review the literature addressing the relationship of growth and nutritional parameters with pulmonary function in pediatric patients with cystic fibrosis. DATA SOURCE: A collection of articles published in the last 15 years in English, Portuguese and Spanish was made by research in electronic databases - PubMed, Cochrane, Medline, Lilacs and Scielo - using the keywords cystic fibrosis, growth, nutrition, pulmonary function in varied combinations. Articles that addressed the long term association of growth and nutritional parameters, with an emphasis on growth, with pulmonary disease in cystic fibrosis, were included, and we excluded those that addressing only the relationship between nutritional parameters and cystic fibrosis and those in which the aim was to describe the disease. DATA SYNTHESIS: Seven studies were included, with a total of 12,455 patients. Six studies reported relationship between growth parameters and lung function, including one study addressing the association of growth parameters, solely, with lung function, and all the seven studies reported relationship between nutritional parameters and lung function. CONCLUSIONS: The review suggests that the severity of the lung disease, determined by spirometry, is associated with body growth and nutritional status in cystic fibrosis. Thus, the intervention in these parameters can lead to the better prognosis and life expectancy for cystic fibrosis patients. PMID- 27181345 TI - Differences in caregivers' cognitive appraisal, coping strategies, and perceived influence on life by care recipients' sex and kinship with primary caregivers. AB - Objectives This study was aimed at examining whether caregivers' cognitive appraisal, coping strategies, and perceived influence on life vary according to care recipients' sex and caregivers' kinship (e.g., spouse, son, daughter, or daughter-in-law).Methods We contacted 1,110 relatively large visiting nursing stations in 37 prefectures, 83 of which agreed to participate in the study. Station managers were requested to select up to 20 families with an elderly person to care for. A questionnaire that included measures for caregivers' cognitive appraisal, coping strategies toward family caregiving, and caregivers' perception, which measures the perceptions of negative and positive influences on family life through caregiving, was administered to the 1,278 families selected by the nursing stations. From this pool, 1,020 questionnaires (79.8%) were returned, completed anonymously by primary caregivers.Results Two-way analysis of variance was used to analyze the care recipients' sex and kinship with primary caregivers. The analysis revealed significant interactions regarding the level of care required and approximately half of the scales measuring cognitive appraisal, coping strategies, and perceived influence on life. The level of care required was higher for male care recipients than for female care recipients when recipients were cared for by their daughters. Husbands caring for wives and daughters-in-law caring for fathers-in-law were more likely to feel "restricted in their social life," have difficulty "keeping pace" with caregiving, and have "negative influence on life." Husbands caring for wives felt less "personal growth through caregiving" than wives caring for husbands. Daughters caring for fathers perceived a lower "positive acceptance of caregiving role" than those caring for mothers. Husbands caring for wives tended not to seek "informal support." Care recipients' sex had little influence on caregivers' cognitive appraisal, coping strategies, and caregivers' perceptions of negative and positive influences on family life. Regarding the main effects of caregivers' kinship, spousal caregivers felt more anxious about continuous caregiving but felt more "fulfilled" and "positively accepted" in their caregiving role.Conclusion Cognitive appraisal and coping strategies toward family caregiving, and the caregivers' perceptions of negative and positive influences on life might vary according to care recipients' sex and caregivers' kinship. Our findings suggest the necessity for long-term care insurance services to incorporate not only care for the care recipients but also a strategy to deal with the psychological burden of family caregivers. PMID- 27181346 TI - The Relationship between Home Environment and Children's Dietary Behaviors, Lifestyle Factors, and Health: Super Food Education School Project by the Japanese Ministry of Education, Culture, Sports, Science and Technology. AB - Objectives The numbers of nuclear families and working women have been increasing. Such changes in the home environment may affect children's dietary behaviors, lifestyle factors, and health. This study aims to clarify the associations between the home environment and children's dietary behaviors, lifestyle factors, and health.Methods In July 2014, we questioned the students and parents of five elementary schools that joined the Super Food Education School Project in Takaoka City, Toyama Prefecture. Of 2057 subjects, 1936 (94.1%) answered and 1719 of these subjects were analyzed. In this study, the phrase "home environment" describes such terms as "mother's employment status", "family structure", "subjective economic state", "communication between parents and children", "having breakfast or supper with family", "household chores by children", "parents' awareness of food education", "regard for balanced nutrition", and "teaching table manners". We performed logistic-regression analyses using children's dietary behaviors, lifestyle factors, and health as dependent variables; the items relating to home environment were independent variables.Results Children with parents who are employed, those who do not have breakfast or supper with family, those who do not help with household chores, and those with parents who are less conscious of food education were more likely to eat fewer vegetables, to have likes and dislikes of foods, to skip breakfast, and to have snacks. Children who have little communication with their parents, who do not help with household chores, and those with parents who are less conscious of food education were less likely to exercise, sleep well, spend less time with television, and spend less time on playing videogames. Children with less affluence, those who have little communication with their parents, those who do not help with household chores, and those with parents who are less conscious of food education were less likely to have high health satisfaction levels, to feel good when waking up, to be calm, or to have good self-affirmation.Conclusion The results of this study show that a good home environment relates to children's good dietary behaviors, positive lifestyle factors, and good health. It is important to maintain a good home environment, such as by raising parents' food awareness, increasing opportunities for communication between children and parents, and having children help with household chores to improve children's dietary behaviors, lifestyle factors, and health. PMID- 27181347 TI - Differences between family caregivers and people with dementia in recognizing the difficulties encountered in the lives of people with dementia. AB - Objectives Dementia brings new difficulties in the lives of people with this disorder. It is important that family caregivers accurately recognize these difficulties to help their family members live fulfilling lives. Based on information gathered from people with dementia, family caregivers, and nurses providing medical care to this population, this study compared the differences in perspectives related to the difficulties associated with dementia between the family member with dementia and the family caregiver.Methods The primary participants in this investigation were 106 people with dementia and their family caregivers. Participants with dementia were 65 years and older who were receiving home care in Tokyo. Participants were interviewed about their difficulties while family caregivers completed a questionnaire with basic information regarding people with dementia. Additionally, the nurse providing medical care to the person with dementia completed a questionnaire about the medical care. In this study, difficulties in the lives of people with dementia was defined as impediments in life due to dementia. Difficulties were classified according to 12 symptoms based on responses that appeared frequently in the interviews. The 12 symptoms were pain, hallucinations/delusions, aggressive behavior, memory loss, disorientation, communication impairment, anxiety/confusion, toileting problems, gait disturbance, dietary deficiency, sleep disorder, and social withdrawal. Additional information was gathered and analyzed that included diagnosis and severity of dementia, need for long-term care, core symptoms of dementia, behavioral and psychological symptoms of dementia (BPSD), and delirium.Results The family caregiver's perspective about the difficulties encountered in the life of their family member with dementia was often different from the perspective of the associated family member. No family caregivers recognized that pain was a difficulty, and there were only a few cases in which pain was treated. Alternatively, many family caregivers recognized that hallucinations/delusions and aggressive behavior were difficulties experienced by people with dementia. There was also a significant correlation between the experience of pain and the presence of a sleep disorder.Conclusion The present results clarified the differences between family caregivers and people with dementia by recognizing the difficulties in life experienced by people with dementia. Such difficulties are not solved by the care performed by family caregivers alone. Further investigation is needed to identify those factors that enable people with dementia to live fulfilling lives. PMID- 27181344 TI - Awareness of Emotional Stimuli Determines the Behavioral Consequences of Amygdala Activation and Amygdala-Prefrontal Connectivity. AB - Conscious awareness of negative cues is thought to enhance emotion-regulatory capacity, but the neural mechanisms underlying this effect are unknown. Using continuous flash suppression (CFS) in the MRI scanner, we manipulated visual awareness of fearful faces during an affect misattribution paradigm, in which preferences for neutral objects can be biased by the valence of a previously presented stimulus. The amygdala responded to fearful faces independently of awareness. However, when awareness of fearful faces was prevented, individuals with greater amygdala responses displayed a negative bias toward unrelated novel neutral faces. In contrast, during the aware condition, inverse coupling between the amygdala and prefrontal cortex reduced this bias, particularly among individuals with higher structural connectivity in the major white matter pathway connecting the prefrontal cortex and amygdala. Collectively, these results indicate that awareness promotes the function of a critical emotion-regulatory network targeting the amygdala, providing a mechanistic account for the role of awareness in emotion regulation. PMID- 27181348 TI - Early detection and response for measles and rubella cases through the (Nursery) School Absenteeism Surveillance System in Ibaraki Prefecture. AB - Objectives In Ibaraki Prefecture, all (nursery) schools have joined the (Nursery) School Absenteeism Surveillance System (hereafter denoted as (N)SASSy), which is operated by the Japan School Health Association to monitor the prevalence of infectious diseases, the early detection and response for outbreaks, and prevention of large outbreaks. Prefectural government officers also utilize it as a control measure for infectious diseases. In particular, when cases of measles or rubella are registered, (N)SASSy sends e-mails automatically to prefectural government officers to activate control measures. This paper summarizes administrative responses by prefectural government officers for measles or rubella cases using (N)SASSy and discusses the future challenges.Methods We summarized registration, detection, and first response data for measles or rubella cases in (N)SASSy and compared the number of detected and reported cases enforced by the Infectious Diseases Control Law from January 1, 2013 to December 31, 2014.Results The public health center questioned hospitals/clinics and (nursery) schools about all registered measles or rubella cases in (N)SASSy on the same day to check the entered information. In the past 2 years, there were 5 measles and 56 rubella cases in 2013 and 1 measles and 19 rubella cases in 2014 registered with (N)SASSy. All cases were checked and investigated by the public health center. Of all cases detected by (N)SASSy, 7 rubella cases in 2013 and 1 rubella case in 2014 were reported based on the law. No measles cases were reported in the 2 years. The results of investigations and laboratory tests were given as feedback to the (nursery) schools. If the case did not case definition determined by the law, we changed the status in (N)SASSy to suspected or discarded cases.Conclusion Since (N)SASSy assists prefectural government officers with earlier detection of and response for infectious diseases, it definitely contributes to infection control. Immediate feedback of the laboratory test results to the (nursery) schools was also useful to confirm cases of measles or rubella. As data entry in (nursery) schools is needed for stable operation and utilization of (N)SASSy, it is important that workshops for (N)SASSy are held for (nursery) school teachers every year to maintain accuracy. Our future challenges include the coordination among (nursery) schools, hospitals/clinics, and prefectural government and their applications for infection control. PMID- 27181349 TI - Biotin augments acetyl CoA carboxylase 2 gene expression in the hypothalamus, leading to the suppression of food intake in mice. AB - It is known that biotin prevents the development of diabetes by increasing the functions of pancreatic beta-cells and improving insulin sensitivity in the periphery. However, its anti-obesity effects such as anorectic effects remain to be clarified. Acetyl CoA carboxylase (ACC), a biotin-dependent enzyme, has two isoforms (ACC1 and ACC2) and serves to catalyze the reaction of acetyl CoA to malonyl CoA. In the hypothalamus, ACC2 increases the production of malonyl CoA, which acts as a satiety signal. In this study, we investigated whether biotin increases the gene expression of ACC2 in the hypothalamus and suppresses food intake in mice administered excessive biotin. Food intake was significantly decreased by biotin, but plasma regulators of appetite, including glucose, ghrelin, and leptin, were not affected. On the other hand, biotin notably accumulated in the hypothalamus and enhanced ACC2 gene expression there, but it did not change the gene expression of ACC1, malonyl CoA decarboxylase (a malonyl CoA-degrading enzyme), and AMP-activated protein kinase alpha-2 (an ACC inhibitory enzyme). These findings strongly suggest that biotin potentiates the suppression of appetite by upregulating ACC2 gene expression in the hypothalamus. This effect of biotin may contribute to the prevention of diabetes by biotin treatment. PMID- 27181351 TI - Toll-interacting protein inhibits HIV-1 infection and regulates viral latency. AB - HIV-1 latency is mainly characterized by a reversible silencing of long-terminal repeat (LTR)-driven transcription of provirus. The existing of repressive factors has been described to contribute to transcription silencing of HIV-1. Toll interacting protein (Tollip) has been identified as a repressor of Toll like receptors (TLR)-mediated signaling. Our previous study has found that Tollip inhibited NF-kappaB-dependent HIV-1 promoter LTR-driven transcription, indicating the potential role of Tollip in governing viral latency. In this study, by using HIV-1 latently infected Jurkat T-cell and central memory CD4(+) T-cells, we demonstrate the role of Tollip in regulating HIV-1 latency, as the knock-down of Tollip promoted HIV-1 reactivation from both HIV-1 latently infected Jurkat CD4(+) T cells and primary central memory T cells (TCM). Moreover, we found that the activities of LTRs derived from multiple HIV-1 subtypes could be repressed by Tollip; Knock-down of Tollip promoted HIV-1 transcription and infection in CD4(+) T cells. Our data indicate a key role of Tollip in suppressing HIV-1 infection and regulating viral latency, which provides a potential host target for combating HIV-1 infection and latency. PMID- 27181350 TI - Abiotic stress of ambient cold temperature regulates the host receptivity to pathogens by cell surfaced sialic acids. AB - Ambient cold temperature, as an abiotic stress, regulates the survival, stability, transmission, and infection of pathogens. However, the effect of cold temperature on the host receptivity to the pathogens has not been fully studied. In this study, the expression of terminal alpha-2,3- and alpha-2,6-sialic acids were increased in murine lung tissues, especially bronchial epithelium, by exposure to cold condition. The expression of several sialyltransferases were also increased by exposure to cold temperature. Furthermore, in human bronchial epithelial BEAS-2B cells, the expressions of alpha-2,3- and alpha-2,6-sialic acids, and mRNA levels of sialyltransferases were increased in the low temperature condition at 33 degrees C. On the other hand, the treatment of Lith Gly, a sialyltransferase inhibitor, blocked the cold-induced expression of sialic acids on surface of BEAS-2B cells. The binding of influenza H1N1 hemagglutinin (HA) toward BEAS-2B cells cultured at low temperature condition was increased, compared to 37 degrees C. In contrast, the cold-increased HA binding was blocked by treatment of lithocholicglycine and sialyl-N-acetyl-D-lactosamines harboring alpha-2,3- and alpha-2,6-sialyl motive. These results suggest that the host receptivity to virus at cold temperature results from the expressions of alpha 2,3- and alpha-2,6-sialic acids through the regulation of sialyltransferase expression. PMID- 27181352 TI - Effect of green light spectra on the reduction of retinal damage and stress in goldfish, Carassius auratus. AB - We investigated the effect of light spectra on retinal damage and stress in goldfish using green (530 nm) and red (620 nm) light emitting diodes (LEDs) at three intensities each (0.5, 1.0, and 1.5 W/m(2)). We measured the change in the levels of plasma cortisol and H2O2 and expression and levels of caspase-3. The apoptotic response of green and red LED spectra was assessed using the terminal transferase dUTP nick end labeling (TUNEL) assay. Stress indicator (cortisol and H2O2) and apoptosis-related genes (caspase-3) decreased in green light, but increased in red light with higher light intensities over time. The TUNEL assay revealed that more apoptotic cells were detected in outer nuclear layers after exposure to red LED over time with the increase in light intensity, than the other spectra. These results indicate that green light efficiently reduces retinal damage and stress, whereas red light induces it. Therefore, red light induced retina damage may induce apoptosis in goldfish retina. PMID- 27181353 TI - Parkin suppresses Drp1-independent mitochondrial division. AB - The cycle of mitochondrial division and fusion disconnect and reconnect individual mitochondria in cells to remodel this energy-producing organelle. Although dynamin-related protein 1 (Drp1) plays a major role in mitochondrial division in cells, a reduced level of mitochondrial division still persists even in the absence of Drp1. It is unknown how much Drp1-mediated mitochondrial division accounts for the connectivity of mitochondria. The role of a Parkinson's disease-associated protein-parkin, which biochemically and genetically interacts with Drp1-in mitochondrial connectivity also remains poorly understood. Here, we quantified the number and connectivity of mitochondria using mitochondria targeted photoactivatable GFP in cells. We show that the loss of Drp1 increases the connectivity of mitochondria by 15-fold in mouse embryonic fibroblasts (MEFs). While a single loss of parkin does not affect the connectivity of mitochondria, the connectivity of mitochondria significantly decreased compared with a single loss of Drp1 when parkin was lost in the absence of Drp1. Furthermore, the loss of parkin decreased the frequency of depolarization of the mitochondrial inner membrane that is caused by increased mitochondrial connectivity in Drp1-knockout MEFs. Therefore, our data suggest that parkin negatively regulates Drp1-indendent mitochondrial division. PMID- 27181354 TI - Puromycin induces SUMO and ubiquitin redistribution upon proteasome inhibition. AB - We have previously reported the co-localization of O-propargyl-puromycin (OP Puro) with SUMO-2/3 and ubiquitin at promyelocytic leukemia-nuclear bodies (PML NBs) in the presence of the proteasome inhibitor MG132, implying a role for the ubiquitin family in sequestering OP-puromycylated immature polypeptides to the nucleus during impaired proteasome activity. Here, we found that as expected puromycin induced SUMO-1/2/3 accumulation with ubiquitin at multiple nuclear foci in HeLa cells when co-exposed to MG132. Co-administration of puromycin and MG132 also facilitated redistribution of PML and the SUMO-targeted ubiquitin ligase RNF4 concurrently with SUMO-2/3. As removal of the drugs from the medium led to disappearance of the SUMO-2/3-ubiquitin nuclear foci, our findings indicated that nuclear assembly/disassembly of SUMO-2/3 and ubiquitin was pharmacologically manipulable, supporting our previous observation on OP-Puro, which predicted the ubiquitin family function in sequestrating aberrant proteins to the nucleus. PMID- 27181355 TI - Crystal structure of Thermotoga maritima acetyl esterase complex with a substrate analog: Insights into the distinctive substrate specificity in the CE7 carbohydrate esterase family. AB - The carbohydrate esterase family 7 (CE7) members are acetyl esterases that possess unusual substrate specificity for cephalosporin C and 7-amino cephalosporanic acid. This family containing the alpha/beta hydrolase fold has a distinctive substrate profile that allows it to carry out hydrolysis of esters containing diverse alcohol moieties while maintaining narrow specificity for an acetate ester. Here we investigate the structural basis of this preference for small acyl groups using the crystal structure of the thermostable Thermotoga maritima CE7 acetyl esterase (TmAcE) complexed with a non-cognate substrate analog. The structure determined at 1.86 A resolution provides direct evidence for the location of the largely hydrophobic and rigid substrate binding pocket in this family. Furthermore, a three-helix insertion domain near the catalytic machinery shapes the substrate binding site. The structure reveals two residues (Pro228 and Ile276) which constitute a hydrophobic rigid binding surface for the acyl group of the ester and thus restricts the size of the acyl group that be accommodated. In combination with previous literature on kinetic properties of the enzyme, our studies suggest that these residues determine the unique specificity of the TmAcE for short straight chain esters. The structure provides a template for focused attempts to engineer the CE7 enzymes for enhanced stability, selectivity or activity for biocatalytic applications. PMID- 27181356 TI - ox-LDL induces endothelial dysfunction by promoting Arp2/3 complex expression. AB - Oxidized low-density lipoproteins (ox-LDL) play a critical role in endothelial injury including cytoskeleton reorganization, which is closely related to actin related protein 2/3 (Arp2/3) complex. The aim of this study was to investigate the role of Arp2/3 complex in ox-LDL-induced endothelial dysfunction. In this study, we found that Arp2 and Arp3 expression was increased under atherosclerotic conditions both in ApoE-/- mice and in ox-LDL-stimulated human coronary artery endothelial cells (HCAECs). Arp2/3 complex inhibitor CK666 significantly reduced ox-LDL-induced ROS generation and cytoskeleton reorganization, and increased NO release in HCAECs. Pretreatment with LOX-1- but not CD36-blocking antibody markedly decreased ox-LDL-induced Arp2 and Arp3 expression. Moreover, Rac-1 siRNA remarkably suppressed ox-LDL-stimulated Arp2 and Arp3 expression. Additionally, CK666 reduced endothelial nitric oxide synthase (eNOS) expression and atherosclerotic lesions in ApoE-/- mice. Collectively, ox-LDL induces endothelial dysfunction by activating LOX-1/Rac-1 signaling and upregulating Arp2/3 complex expression. PMID- 27181358 TI - microRNA-328 inhibits cervical cancer cell proliferation and tumorigenesis by targeting TCF7L2. AB - microRNAs (miRNAs) play a vital role in tumor development and progression. In this study, we aimed to determine the expression and biological roles of miR-328 in cervical cancer and identify its direct target gene. Our data showed that miR 328 was significantly downregulated in human cervical cancer tissues and cells. Re-expression of miR-328 inhibited cervical cancer cell proliferation and colony formation in vitro and suppressed the growth of xenograft tumors in vivo. Bioinformatic analysis predicted TCF7L2 (an essential effector of canonical Wnt signaling) as a target gene of miR-328, which was confirmed by luciferase reporter assays. Enforced expression of miR-328 led to a decline in the expression of endogenous TCF7L2 in cervical cancer cells. In cervical cancer tissues, TCF7L2 protein levels were negatively correlated with miR-328 expression levels (r = -0.462, P = 0.017). Small interfering RNA-mediated knockdown of TCF7L2 significantly impaired the proliferation and colony formation of cervical cancer cells. Ectopic expression of a miRNA-resistant form of TCF7L2 significantly reversed the growth suppressive effects of miR-328 on cervical cancer cells, which was accompanied by induction of cyclin D1 expression. Taken together, our results provide first evidence for the growth suppressive activity of miR-328 in cervical cancer, which is largely ascribed to downregulation of TCF7L2. Restoration of miR-328 may have therapeutic potential in cervical cancer. PMID- 27181357 TI - Identification of IgM as a contaminant in lectin-FLISA assays for HCC detection. AB - Liver disease, in the form of hepatocellular carcinoma (HCC) accounts for > 700,000 deaths worldwide. A major reason for this is late diagnosis of HCC. The currently used biomarker, serum alpha-fetoprotein (AFP) is elevated in 40-60% of those with HCC and other markers that can either compliment or replace AFP are desired. Our previous work has identified a number of proteins that contain altered glycans in HCC. Specifically, these altered glycans were increased levels of core and outer arm fucosylation. To determine the clinical usefulness of those identified glycoproteins, a plate based assay was developed that allowed for the detection of fucosylated glycoforms. While this method was applicable to a number of independent patient sets, it was unable to specifically detect fucosylated glycoforms in many patient samples. That is, some material was present in serum that led to non-specific signal in the lectin- fluorescence -linked immunosorbent assay (lectin-FLISA). To address this issue, a systematic process was undertaken to identify the material. This material was found to be increased levels of lectin reactive IgM. Removal of both IgG and IgM using a multi-step protein A/G incubation and filtration step removed the contaminating signal and allowed for the analysis of specific protein glycoforms. This assay was subsequently used on two sample sets, one that was shown previously to be unable to be tested via a lectin FLISA and in a larger independent sample set. The clinical usefulness of this assay in the early detection of HCC is discussed. PMID- 27181359 TI - Production, characterization, and in vitro effects of a novel monoclonal antibody against Mig-7. AB - Development of new cancer therapies based on specific recognition of molecules in cancer cells is a significant challenge, as this requires identification of such molecules (molecular targets) and subsequent development of high-affinity, selective binders (targeting molecules). While several molecular targets for cancer therapies are currently under evaluation in clinical trials, greater selectivity for cancer cells over normal cells is required to enhance efficacy. Migration-inducing gene 7 (Mig-7), a membrane protein found in various types of carcinoma cells, is a cancer-specific biomarker and a promising molecular target for targeted cancer therapies. The purpose of this study was to produce and characterize a novel monoclonal antibody (mAb) raised against an N-terminal peptide of human Mig-7 (Mig-7(1-30)). The Mig-7(1-30) peptide was conjugated with a KLH carrier protein for immunization, and the mAb specific to Mig-7 (STmAb-1) was produced using hybridoma technology. Western blot analysis showed that STmAb 1 specifically reacted with a 23-kDa Mig-7 protein expressed in cancer cell lines, and, crucially, not with primary human fibroblasts. The affinity constant (Kaff) of STmAb-1, as measured by non-competitive enzyme immunoassay, was 1.31 * 10(9) M(-1), indicating high mAb affinity against Mig-7. Immunofluorescence assays demonstrated that STmAb-1 could specifically recognize Mig-7 expressed in cancer cell lines, but not in primary human fibroblasts and keratinocytes. Moreover, STmAb-1 inhibited the growth of MCF7 and HeLa cell lines in contrast to primary human fibroblasts, highlighting its potential usefulness in the development of new cancer therapeutics. PMID- 27181360 TI - Iron participated in breast cancer chemoresistance by reinforcing IL-6 paracrine loop. AB - Chemotherapeutic efficacy is also regulated by the tumor microenvironment. IL-6 produced by TAMs and downstream IL-6/STAT3 signaling pathway is central regulator in chemotherapeutic response. The M2-like phenotype of TAMs is characterized by elevated iron uptake. Whether iron participates in chemo-resistance need to be elucidated. In the present study, we found that IL-6 participated in breast cancer chemoresistance. Local IL-6 paracrine loop acted as exogenous IL-6 rich niche for chemo-sensitive breast cancer cells, leading to de novo acquired drug resistance. Furthermore, Iron reinforced the IL-6 paracrine loop between TAMs and tumor cells resulting in enhanced chemo-resistance. Targeting iron metabolism could disturb the reciprocal interaction between tumor cells and TAMs, breaking the local IL-6 rich niche and blocking IL-6 signaling pathway, which could be promising strategy to overcome chemo-resistance. PMID- 27181361 TI - PAX5 tyrosine phosphorylation by SYK co-operatively functions with its serine phosphorylation to cancel the PAX5-dependent repression of BLIMP1: A mechanism for antigen-triggered plasma cell differentiation. AB - Plasma cell differentiation is initiated by antigen stimulation of the B cell receptor (BCR) and is regulated by BLIMP1. Prior to the stimulation of BCR, BLIMP1 is suppressed by PAX5, which is a key transcriptional repressor that maintains B cell identity. The upregulation of BLIMP1 and subsequent suppression of PAX5 by BLIMP1 are observed after the BCR stimulation. These events are considered to trigger plasma cell differentiation; however, the mechanisms responsible currently remain unclear. We herein demonstrated that the BCR signaling component, SYK, caused PAX5 tyrosine phosphorylation in vitro and in cells. Transcriptional repression on the BLIMP1 promoter by PAX5 was attenuated by this phosphorylation. The BCR stimulation induced the phosphorylation of SYK, tyrosine phosphorylation of PAX5, and up-regulation of BLIMP1 mRNA expression in B cells. The tyrosine phosphorylation of PAX5 co-operatively functioned with PAX5 serine phosphorylation by ERK1/2, which was our previous findings, to cancel the PAX5-dependent repression of BLIMP1. This co-operation may be a trigger for plasma cell differentiation. These results imply that PAX5 phosphorylation by a BCR signal is the initial event in plasma cell differentiation. PMID- 27181362 TI - HIF-1alpha activates hypoxia-induced PFKFB4 expression in human bladder cancer cells. AB - PFKFB4 is reported to regulate glycolysis by synthesizing fructose-2, 6 bisphosphate (F2,6BP) and has proved to be associated with most malignancies. However, the underlying mechanism for increased PFKFB4 expression in bladder cancer remains unclear. The present study demonstrated that PFKFB4 was overexpressed in bladder cancer tissues. In addition, the expression of PFKFB4 elevated in bladder cancer cells in the hypoxic condition, while in nomoxic condition, the expression of PFKFB4 still very low. Furthermore, we identified the hypoxia-responsive elements (HRE)-D from five putative HREs in the promoter region of PFKFB4 and demonstrated that the HRE-D was transactivated by the HIF 1alpha in bladder cancer cells. By using the Double-immunofluorescence co localization assay, we revealed that the HIF-1alpha expression was associated with PFKFB4 expression in human bladder cancer specimens. Altogether, our study for the first time identified the pivotal role of HIF-1alpha in the connection between PFKFB4 and hypoxia in bladder cancer, which may prove to be a potential target for the treatment of bladder cancer. PMID- 27181364 TI - An integrated soil-crop system model for water and nitrogen management in North China. AB - An integrated model WHCNS (soil Water Heat Carbon Nitrogen Simulator) was developed to assess water and nitrogen (N) management in North China. It included five main modules: soil water, soil temperature, soil carbon (C), soil N, and crop growth. The model integrated some features of several widely used crop and soil models, and some modifications were made in order to apply the WHCNS model under the complex conditions of intensive cropping systems in North China. The WHCNS model was evaluated using an open access dataset from the European International Conference on Modeling Soil Water and N Dynamics. WHCNS gave better estimations of soil water and N dynamics, dry matter accumulation and N uptake than 14 other models. The model was tested against data from four experimental sites in North China under various soil, crop, climate, and management practices. Simulated soil water content, soil nitrate concentrations, crop dry matter, leaf area index and grain yields all agreed well with measured values. This study indicates that the WHCNS model can be used to analyze and evaluate the effects of various field management practices on crop yield, fate of N, and water and N use efficiencies in North China. PMID- 27181365 TI - Structural evolution and metallicity of lead clusters. AB - The evolution of the metallic state in lead clusters and its structural implications are subject to ongoing discussions. Here we present molecular beam electric deflection studies of neutral PbN (N = 19-25, 31, 36, 54) clusters. Many of them exhibit dipole moments or anomalies of the polarizability indicating a non-metallic state. In order to resolve their structures, the configurational space is searched using the Pool Birmingham Cluster Genetic algorithm based on density functional theory. Spin-orbit effects on the geometries and dipole moments are taken into account by further relaxing them with two-component density functional theory. Geometries and dielectric properties from quantum chemical calculations are then used to simulate beam deflection profiles. Structures are assigned by the comparison of measured and simulated beam profiles. Energy gaps are calculated using time-dependent density functional theory. They are compared to Kubo gaps, which are an indicator of the metallicity in finite particles. Both, experimental and theoretical data suggest that lead clusters are not metallic up to at least 36 atoms. PMID- 27181363 TI - Clinical predictive factors in diabetic kidney disease progression. AB - Diabetic kidney disease (DKD) represents a major component of the health burden associated with type 1 and type 2 diabetes. Recent advances have produced an explosion of 'novel' assay-based risk markers for DKD, though clinical use remains restricted. Although many patients with progressive DKD follow a classical albuminuria-based pathway, non-albuminuric DKD progression is now well recognized. In general, the following clinical and biochemical characteristics have been associated with progressive DKD in both type 1 and type 2 diabetes: increased hemoglobin A1c, systolic blood pressure, albuminuria grade, early glomerular filtration rate decline, duration of diabetes, age (including pubertal onset) and serum uric acid; the presence of concomitant microvascular complications; and positive family history. The same is true in type 2 diabetes for male sex category, in patients following an albuminuric pathway to DKD, and also true for the presence of increased pulse wave velocity. The following baseline clinical characteristics have been proposed as risk factors for DKD progression, but with further research required to assess the nature of any relationship: dyslipidemia (including low-density lipoprotein, total and high density lipoprotein cholesterol); elevated body mass index; smoking status; hyperfiltration; decreases in vitamin D, hemoglobin and uric acid excretion (all known consequences of advanced DKD); and patient test result visit-to-visit variability (hemoglobin A1c, blood pressure and high-density lipoprotein cholesterol). The development of multifactorial 'renal risk equations' for type 2 diabetes has the potential to simplify the task of DKD prognostication; however, there are currently none for type 1 diabetes-specific populations. Significant progress has been made in the prediction of DKD progression using readily available clinical data, though further work is required to elicit the role of several variables, and to consolidate data to facilitate clinical implementation. PMID- 27181366 TI - Cytoplasmic cyclin D1 regulates cell invasion and metastasis through the phosphorylation of paxillin. AB - Cyclin D1 (Ccnd1) together with its binding partner Cdk4 act as a transcriptional regulator to control cell proliferation and migration, and abnormal Ccnd1.Cdk4 expression promotes tumour growth and metastasis. While different nuclear Ccnd1.Cdk4 targets participating in cell proliferation and tissue development have been identified, little is known about how Ccnd1.Cdk4 controls cell adherence and invasion. Here, we show that the focal adhesion component paxillin is a cytoplasmic substrate of Ccnd1.Cdk4. This complex phosphorylates a fraction of paxillin specifically associated to the cell membrane, and promotes Rac1 activation, thereby triggering membrane ruffling and cell invasion in both normal fibroblasts and tumour cells. Our results demonstrate that localization of Ccnd1.Cdk4 to the cytoplasm does not simply act to restrain cell proliferation, but constitutes a functionally relevant mechanism operating under normal and pathological conditions to control cell adhesion, migration and metastasis through activation of a Ccnd1.Cdk4-paxillin-Rac1 axis. PMID- 27181367 TI - Upper-Airway Collapsibility and Loop Gain Predict the Response to Oral Appliance Therapy in Patients with Obstructive Sleep Apnea. AB - RATIONALE: Oral appliances (OAs) are commonly used as an alternative treatment to continuous positive airway pressure for patients with obstructive sleep apnea (OSA). However, OAs have variable success at reducing the apnea-hypopnea index (AHI), and predicting responders is challenging. Understanding this variability may lie with the recognition that OSA is a multifactorial disorder and that OAs may affect more than just upper-airway anatomy/collapsibility. OBJECTIVES: The objectives of this study were to determine how OA alters AHI and four phenotypic traits (upper-airway anatomy/collapsibility and muscle function, loop gain, and arousal threshold), and baseline predictors of which patients gain the greatest benefit from therapy. METHODS: In a randomized crossover study, 14 patients with OSA attended two sleep studies with and without their OA. Under each condition, AHI and the phenotypic traits were assessed. Multiple linear regression was used to determine independent predictors of the reduction in AHI. MEASUREMENTS AND MAIN RESULTS: OA therapy reduced the AHI (30 +/- 5 vs. 11 +/- 2 events/h; P < 0.05), which was driven by improvements in upper-airway anatomy/collapsibility under passive (1.9 +/- 0.7 vs. 4.7 +/- 0.6 L/min; P < 0.005) and active conditions (2.4 +/- 0.9 vs. 6.2 +/- 0.4 L/min; P < 0.001). No changes were seen in muscle function, loop gain, or the arousal threshold. Using multivariate analysis, baseline passive upper-airway collapsibility and loop gain were independent predictors of the reduction in AHI (r2 = 0.70; P = 0.001). CONCLUSIONS: Our findings suggest that OA therapy improves the upper-airway collapsibility under passive and active conditions. Importantly, a greater response to therapy occurred in those patients with a mild anatomic compromise and a lower loop gain. PMID- 27181369 TI - Timing is everything for sperm assessment in fertility studies. AB - The fertility study design recommended in the ICH S5(R2) Harmonised Guideline for Detection of Toxicity to Reproduction for Medicinal Products emphasizes the importance of histopathological endpoints next to a pairing assessment in evaluating male fertility. However, in a male rat fertility study with JNJ 26489112, a CNS-active agent, while there were no effects on histological endpoints, mating performance or pregnancy outcomes, sperm assessment was included. The high dose males presented with reversible decreases in epididymal, but not testicular, sperm concentration and motility and an increase in abnormal sperm morphology. In view of the differences in fertility between rats and humans, these types of sperm effects in rats suggest the potential for an impact on human male fertility that would be undetected if not for the sperm assessment. Therefore, the current example suggests that including semenology as a standard endpoint in nonclinical fertility studies may be warranted. PMID- 27181370 TI - Entrapment of laurel lipase in chitosan hydrogel beads. AB - Laurel seed lipase was entrapped within chitosan beads with ionotropic gelatin method using tripolyphosphate (TPP) as multivalent covalent counter ion. Immobilization yield was 78%. First, optimum immobilization conditions were determined, and morphology of chitosan beads was characterized by scanning electron microscopy. Optimum pH and temperature were evaluated as 6.0 and 40 degrees C, respectively. The immobilized beads saved about 55% of its activities at 60 degrees while saved about 32% at 70 degrees C for 30 min. Vmax/Km values were determined as 31.75 and 2.87 using olive oil as substrate for immobilized beads and free enzyme, respectively. Immobilized beads showed the activities during 30 days at +4 degrees C. PMID- 27181368 TI - The nuclear receptor NOR-1 regulates the small muscle protein, X-linked (SMPX) and myotube differentiation. AB - Recent works have highlighted the role of NOR-1 in both smooth and skeletal muscle, and have proposed this nuclear receptor as a nexus that coordinates muscle performance and metabolic capacity. However, no muscle specific genes regulated by NOR-1 have been identified so far. To identify NOR-1 target genes, we over-expressed NOR-1 in human vascular smooth muscle cells (VSMC). These cells subjected to sustained over-expression of supraphysiological levels of NOR-1 experienced marked phenotypic changes and up-regulated the skeletal muscle protein X-linked (SMPX), a protein typically expressed in striated muscle and associated to cell shape. By transcriptional studies and DNA-protein binding assays, we identified a non-consensus NBRE site in human SMPX promoter, critical for NOR-1 responsiveness. The expression of SMPX was higher in human skeletal muscle myoblasts (HSMM) than in human VSMC, and further increased in HSMM differentiated to myotubes. NOR-1 silencing prevented SMPX expression in HSMM, as well as their differentiation to myotubes, but the up-regulation of SMPX was dispensable for HSMM differentiation. Our results indicate that NOR-1 regulate SMPX in human muscle cells and acts as a muscle regulatory factor, but further studies are required to unravel its role in muscle differentiation and hypertrophy. PMID- 27181371 TI - Relationship between cancer mutations and parameter sensitivity in Rb pathway. AB - It has long been known that formation of all sorts of tumors is largely owing to the genomic variations. Oncogenic mutations are often found focused on one or more important pathways which indicate that it is meaningful to investigate oncogenic mutations and oncogenic mechanisms from the point of view of biological network. Recently, we found that in apoptosis pathway of mammalian cell, mutations that cause large variations on the bifurcation point are more probably oncogenic mutations. Here, we used the Rb-E2F pathway in mammalian cell in response to growth factor as another example to verify this correlation. To conduct this study, nonlinear dynamics equations that describe the behavior of the Rb-E2F pathway was first constructed. Then we identified sensitive parameters which have a great influence on the system's bifurcation point. And we found that the sensitive parameters are highly related to high-frequency oncogenic mutations after comparing the results of parameter sensitivity analysis with profile of known cancer mutations. Moreover, the position of bifurcation point rather than concentration of a certain protein is a better measurement to determine biological network's function. Our results further confirm that nonlinear dynamics analysis of biological networks is an important way to understand oncogenesis. And the analysis method can become a powerful tool to understand and analyze the function of biological network. PMID- 27181372 TI - Genetic risks and genetic model specification. AB - Genetic risks and genetic models are often used in design and analysis of genetic epidemiology studies. A genetic model is defined in terms of two genetic risk measures: genotype relative risk and odds ratio. The impacts of choosing a risk measure on the resulting genetic models are studied in the power to detect association and deviation from Hardy-Weinberg equilibrium in cases using genetic relative risk. Extensive simulations demonstrate that the power of a study to detect associations using odds ratio is lower than that using relative risk with the same value when other parameters are fixed. When the Hardy-Weinberg equilibrium holds in the general population, the genetic model can be inferred by the deviation from Hardy-Weinberg equilibrium in only cases. Furthermore, it is more efficient than that based on the deviation from Hardy-Weinberg equilibrium in all cases and controls. PMID- 27181373 TI - Corrigendum: From the Au nano-clusters to the nanoparticles on 4H-SiC (0001). PMID- 27181375 TI - Reply to: Regarding the Article: Does Iodine Excess Lead to Hypothyroidism? Evidence from A Case-Control Study in India. PMID- 27181376 TI - Current Status of Childhood Hyperinsulinemic Hypoglycemia in Turkey. AB - Congenital hyperinsulinism (CHI) is a rare disease characterized by dysregulated insulin secretion from pancreatic beta-cells. Recurrent hypoglycemia can lead to neurological insult and permanent brain injury. Recently, there are important advances in understanding the genetic mechanisms, histological characteristics, imaging, and surgical techniques of congenital hyperinsulinemic hypoglycemia that could reflect to improvement in the clinical care of infants with this disorder. In Turkey, there is a high rate of consanguinity, thus, the incidence of CHI is expected to be high. Until now, there are no nationwide data regarding the disorder, and some individual case reports or case series had been published. Determining the characteristics of Turkish patients with CHI can help develop a different perspective on this rare disease. In this review, we evaluated the clinical and molecular characteristics of Turkish patients with CHI based on reports published in the literature. The most frequently seen mutations were ABCC8 gene mutations (n=37), followed by HADH (n=11) and KCNJ11 gene (n=7) mutations. A total of 141 Turkish patients with CHI were reported until now. Among them, 115 patients had been genetically analyzed, and 56 of them had one of the mutation leading to hyperinsulinism. PMID- 27181377 TI - Anti-herpesviral effects of a novel broad range anti-microbial quaternary ammonium silane, K21. AB - We have created a novel quaternary ammonium silane, K21 through sol-gel chemistry, using an ethoxylated version of an organosilane quaternary ammonium compound and TetraEthyl Ortho Silicate (TEOS) as precursors. Previous studies using the precursor molecule quaternary ammonium compounds (QACs) and a methacryloxy version of K21, primarily designed for use in dental healthcare, have shown inhibited growth properties against several types of gram-positive and gram-negative bacteria including Escherichia coli, Streptococcus mutans, Actinomyces naeslundii and Candida albicans etc. Here we tested the effect of K21 on HSV-1, HHV-6A and HHV-7 in in vitro cell culture infection models. Our results show growth inhibitory effect of K21 on HSV-1, HHV-6A and HHV-7 infection. PMID- 27181374 TI - Neutrophils in type 1 diabetes. AB - Type 1 diabetes is an autoimmune disease that afflicts millions of people worldwide. It occurs as the consequence of destruction of insulin-producing pancreatic beta-cells triggered by genetic and environmental factors. The initiation and progression of the disease involves a complicated interaction between beta-cells and immune cells of both innate and adaptive systems. Immune cells, such as T cells, macrophages and dendritic cells, have been well documented to play crucial roles in type 1 diabetes pathogenesis. However, the particular actions of neutrophils, which are the most plentiful immune cell type and the first immune cells responding to inflammation, in the etiology of this disease might indeed be unfairly ignored. Progress over the past decades shows that neutrophils might have essential effects on the onset and perpetuation of type 1 diabetes. Neutrophil-derived cytotoxic substances, including degranulation products, cytokines, reactive oxygen species and extracellular traps that are released during the process of neutrophil maturation or activation, could cause destruction to islet cells. In addition, these cells can initiate diabetogenic T cell response and promote type 1 diabetes development through cell-cell interactions with other immune and non-immune cells. Furthermore, relevant antineutrophil therapies have been shown to delay and dampen the progression of insulitis and autoimmune diabetes. Here, we discuss the relationship between neutrophils and autoimmune type 1 diabetes from the aforementioned aspects to better understand the roles of these cells in the initiation and development of type 1 diabetes. PMID- 27181378 TI - Novel antiviral activity of bromocriptine against dengue virus replication. AB - Dengue virus (DENV) infectious disease is a major public health problem worldwide; however, licensed vaccines or specific antiviral drugs against this infection are not available. To identify novel anti-DENV compounds, we screened 1280 pharmacologically active compounds using focus reduction assay. Bromocriptine (BRC) was found to have potent anti-DENV activity and low cytotoxicity (half maximal effective concentration [EC50], 0.8-1.6 MUM; and half maximal cytotoxicity concentration [CC50], 53.6 MUM). Time-of-drug-addition and time-of-drug-elimination assays suggested that BRC inhibits translation and/or replication steps in the DENV life cycle. A subgenomic replicon system was used to verify that BRC restricts RNA replication step. Furthermore, a single amino acid substitution (N374H) was detected in the NS3 protein that conferred resistance to BRC. In summary, BRC was found to be a novel DENV inhibitor and a potential candidate for the treatment of DENV infectious disease. PMID- 27181381 TI - High-pressure minerals in eucrite suggest a small source crater on Vesta. AB - High-pressure minerals in meteorites are important records of shock events that have affected the surfaces of planets and asteroids. A widespread distribution of impact craters has been observed on the Vestan surface. However, very few high pressure minerals have been discovered in Howardite-Eucrite-Diogenite (HED) meteorites. Here we present the first evidence of tissintite, vacancy-rich clinopyroxene, and super-silicic garnet in the eucrite Northwest Africa (NWA) 8003. Combined with coesite and stishovite, the presence of these high-pressure minerals and their chemical compositions reveal that solidification of melt veins in NWA 8003 began at a pressure of >~10 GPa and ceased when the pressure dropped to <~8.5 GPa. The shock temperature in the melt veins exceeded 1900 degrees C. Simulation results show that shock events that create impact craters of ~3 km in diameter (subject to a factor of 2 uncertainty) are associated with sufficiently high pressures to account for the occurrence of the high-pressure minerals observed in NWA 8003. This indicates that HED meteorites containing similar high pressure minerals should be observed more frequently than previously thought. PMID- 27181382 TI - Novel role for the CRTC2 in lipid homeostasis. AB - The mTOR pathways involved in the regulation of SREBP-1. PMID- 27181379 TI - CDKN2A and BAP1 germline mutations predispose to melanoma and mesothelioma. AB - BAP1 germline mutations predispose to a cancer predisposition syndrome that includes mesothelioma, cutaneous melanoma, uveal melanoma and other cancers. This co-occurrence suggests that these tumors share a common carcinogenic pathway. To evaluate this hypothesis, we studied 40 Italian families with mesothelioma and/or melanoma. The probands were sequenced for BAP1 and for the most common melanoma predisposition genes (i.e. CDKN2A, CDK4, TERT, MITF and POT1) to investigate if these genes may also confer susceptibility to mesothelioma. In two out of six families with both mesothelioma and melanoma we identified either a germline nonsense mutation (c.1153C > T, p.Arg385*) in BAP1 or a recurrent pathogenic germline mutation (c.301G > T, p.Gly101Trp) in CDKN2A. Our study suggests that CDKN2A, in addition to BAP1, could be involved in the melanoma and mesothelioma susceptibility, leading to the rare familial cancer syndromes. It also suggests that these tumors share key steps that drive carcinogenesis and that other genes may be involved in inherited predisposition to malignant mesothelioma and melanoma. PMID- 27181383 TI - The impact of members of the Society of University Surgeons on the scholarship of American surgery. AB - BACKGROUND: A core objective of the Society of University Surgeons (SUS) is research focused: to "advance the art and science of surgery through original investigation." This study sought to determine the current impact of the SUS on academic surgical productivity. METHODS: Individual faculty data for numbers of publications, citations, and National Institute of Health (NIH) funding history were collected for 4,015 surgical faculty at the top 55 NIH-funded departments of surgery using SCOPUS and the NIH Research Portfolio Online Reporting Tools. SUS membership was determined from membership registry data. RESULTS: Overall, 502 surgical faculty (12.5%) were SUS members with 92.7% holding positions of associate or full professor (versus 59% of nonmembers). Median publications (P) and citations (C) among SUS members were P: 112, C: 2,460 versus P: 29, C: 467 for nonmembers (P < .001). Academic productivity was considerably higher by rank for SUS members than for nonmembers: associate professors (P: 61 vs 36, C: 1,199 vs 591, P < .001) and full professors (P: 141 vs 81, C: 3,537 vs 1,856, P < .001). Among full professors, SUS members had much higher rates of NIH funding than did nonmembers (52.6% vs 26%, P < .05) and specifically for R01, P01, and U01 awards (37% vs 17.7%, P < .01). SUS members were 2 times more likely to serve in divisional leadership or chair positions (23.5% vs 10.2%, P < .05). CONCLUSION: SUS society members are a highly productive academic group. These data support the premise that the SUS is meeting its research mission and identify its members as very academically productive contributors to research and scholarship in American surgery and medicine. PMID- 27181384 TI - Reply to: The necessary preoperative dose of alpha-blockers reflects higher tumor activity in pheochromocytoma. PMID- 27181386 TI - Commentary on: Post-thyroidectomy hypocalcemia is related to parathyroid dysfunction even in patients with normal parathyroid hormone concentrations early after surgery. PMID- 27181385 TI - Response to comments on: Cosyntropin stimulation testing on postoperative day 1 allows for selective glucocorticoid replacement therapy following adrenalectomy for hypercortisolism: Results of a novel, multidisciplinary institutional protocol. PMID- 27181387 TI - Analysis of needs of the critically ill relatives and critical care professional's opinion. AB - OBJECTIVE: To describe the needs of the families of patients admitted to the Intensive Care Unit (ICU) and the opinion of ICU professionals on aspects related to the presence of patient relatives in the unit. DESIGN: A prospective descriptive study was carried out between March and June 2015. SETTING: Polyvalent ICU of Leon University Healthcare Complex (Spain). PARTICIPANTS: Two samples of volunteers were studied: one comprising the relatives emotionally closest to the primarily non-surgical patients admitted to the Unit for over 48hours, and the other composed of ICU professionals with over three months of experience in the ICU. INTERVENTION: One self-administered questionnaire was delivered to each relative and another to each professional. MAIN VARIABLES OF INTEREST: Sociodemographic data were collected. The variables in the questionnaire for relatives comprised the information received, closeness to the patient, safety of care, the support received, and comfort. In turn, the questionnaire for professionals addressed empathy and professional relationship with the family, visiting policy, and the effect of the family upon the patient. RESULTS: A total of 59% of the relatives (35/61) answered the questionnaire. Of these subjects, 91.4% understood the information received, though 49.6% received no information on nursing care. A total of 82.9% agreed with the visiting policy applied (95.2% were patient offspring; P<.05). Participation on the part of the professionals in turn reached 76.3% (61/80). A total of 59.3% would flexibilize the visiting policy, and 78.3% considered that the family afforded emotional support for the patient, with no destabilizing effect. On the other hand, 62.3% routinely informed the family, and 88% considered training in communication skills to be needed. CONCLUSIONS: Information was adequate, though insufficient in relation to nursing care. The professionals pointed to the need for training in communication skills. PMID- 27181388 TI - Summary of the 2016 American Association for Cancer Research (AACR) Annual Meeting. PMID- 27181389 TI - Stratification of endometrioid endometrial cancer patients into risk levels using somatic mutations. AB - OBJECTIVE: Patients with endometrioid endometrial cancer are stratified as high risk and low risk for extrauterine disease by surgical staging. Since patients with low-grade, minimally invasive disease do not benefit from comprehensive staging, pre-surgery stratification into a risk category may prevent unnecessary surgical staging in low risk patients. Our objective was to develop a predictive model to identify risk levels using somatic mutations that could be used preoperatively. METHODS: We classified endometrioid endometrial cancer patients in The Cancer Genome Atlas (TCGA) dataset into high risk and low risk categories: high risk patients presented with stage II, III or IV disease or stage I with high-intermediate risk features, whereas low risk patients consisted of the remaining stage I patients with either no myometrial invasion or low-intermediate risk features. Three strategies were used to build the prediction model: 1) mutational status for each gene; 2) number of somatic mutations for each gene; and 3) variant allele frequencies for each somatic mutation for each gene. RESULTS: Each prediction strategy had a good performance, with an area under the curve (or AUC) between 61% and 80%. Analysis of variant allele frequency produced a superior prediction model for risk levels of endometrial cancer as compared to the other two strategies, with an AUC=91%. Lasso and Ridge methods identified 53 mutations that together had the highest predictability for high risk endometrioid endometrial cancer. CONCLUSIONS: This prediction model will assist future retrospective and prospective studies to categorize endometrial cancer patients into high risk and low risk in the preoperative setting. PMID- 27181390 TI - Cardiac Surgery is Safe in Female Patients with a History of Breast Cancer. AB - PURPOSE: In cardiac surgery candidates, a concomitant history of breast cancer suggests adverse outcomes. The possibility of internal mammary artery (IMA) utilization and its patency rate is frequently discussed. Secondary, blood loss and wound related infections might be important issues. However, publications focusing on these issues are limited. METHODS: We analyzed 32 patients with previously treated breast cancer undergoing cardiac bypass (CABG) and combined CABG surgery matched to 99 control subjects in a retrospective cohort study. Patients were analyzed regarding IMA utilization, blood loss and substitution and frequent perioperative complications as well as long-term mortality. RESULTS: No significant differences between groups were observed regarding duration of surgery, IMA-utilization, incidence of infections and postoperative complications or mortality. A pronounced decline of hemoglobin/hematocrit was evident within the first 6 postoperative hours (3.3 +/- 1.8 vs. 2.5 +/- 1.8 mg/dl; p = 0.03) in breast cancer patients not related to an increased drainage loss but associated with an increase of international normalized ratio (INR) (0.39 +/- 0.16 vs. 0.29 +/- 0.24; p <0.01). CONCLUSION: In breast cancer patients, CABG and combined CABG procedures can safely be performed with comparable short- and long-term results. PMID- 27181391 TI - Prevalence of type 2 diabetes mellitus among inland residents in China (2000 2014): A meta-analysis. AB - AIMS/INTRODUCTION: Besides the aging population in China, the following have become serious public health problems: increasing urban population, lifestyle changes and diabetes. We assessed the epidemiology of type 2 diabetes mellitus in China between 2000 and 2014, and analyzed time trends to better determine the prevalence status of diabetes in China and to provide a basis for prevention and decision-making. MATERIALS AND METHODS: In our systematic review, we searched China National Knowledge Infrastructure, Chinese VIP Information, Wanfang and PubMed databases for studies on type 2 diabetes mellitus between 2000 and 2014 in China. Two investigators extracted the data and assessed the quality of the included literature independently. We excluded studies that did not use 1999 World Health Organization criteria for diabetes. We also excluded reviews and viewpoints, studies with insufficient data, studies that were not carried out in mainland China and studies on troops, community, schools or physical examination people. We used stata 12.0 to combine the prevalence of all studies, calculated the pooled prevalence and its 95% confidence interval, and analyzed the differences among men/women, urban/rural areas and year of study. We calculated the prevalence of seven geographic areas of China, respectively, and mapped the distribution in the whole country to estimate the pooled prevalence of each area. RESULTS: Our search returned 4,572 studies, 77 of which satisfied the inclusion criteria. The included studies had a total of 1,287,251 participants, in which 680,574 cases of type 2 diabetes mellitus were recorded. The overall prevalence (9.1%) has been increasing since the 1970s, and it increased rapidly with age. The prevalence of the 65-74 years group was as high as 14.1%. Meanwhile, the prevalence among men/women and urban/rural areas was significantly different. The prevalence was 9.9% for men and 11.6% for women, which were significantly higher than the average at the end of the last century and the beginning of this century. The prevalence rate in urban areas (11.4%) was significantly higher than that in rural areas and in urban-rural fringe areas, and the prevalence in rural areas (8.2%) was slightly higher than that in urban-rural fringe areas (7.5%). In addition, the prevalence in each geographic area were estimated and mapped, which showed a large imbalance in the map. CONCLUSIONS: Our analysis suggested that type 2 diabetes mellitus is highly prevalent in China. These results underscore the urgent need for the government to vigorously strengthen the management of diabetes prevention and control. PMID- 27181392 TI - Natural emulsifiers - Biosurfactants, phospholipids, biopolymers, and colloidal particles: Molecular and physicochemical basis of functional performance. AB - There is increasing consumer pressure for commercial products that are more natural, sustainable, and environmentally friendly, including foods, cosmetics, detergents, and personal care products. Industry has responded by trying to identify natural alternatives to synthetic functional ingredients within these products. The focus of this review article is on the replacement of synthetic surfactants with natural emulsifiers, such as amphiphilic proteins, polysaccharides, biosurfactants, phospholipids, and bioparticles. In particular, the physicochemical basis of emulsion formation and stabilization by natural emulsifiers is discussed, and the benefits and limitations of different natural emulsifiers are compared. Surface-active polysaccharides typically have to be used at relatively high levels to produce small droplets, but the droplets formed are highly resistant to environmental changes. Conversely, surface-active proteins are typically utilized at low levels, but the droplets formed are highly sensitive to changes in pH, ionic strength, and temperature. Certain phospholipids are capable of producing small oil droplets during homogenization, but again the droplets formed are highly sensitive to changes in environmental conditions. Biosurfactants (saponins) can be utilized at low levels to form fine oil droplets that remain stable over a range of environmental conditions. Some nature-derived nanoparticles (e.g., cellulose, chitosan, and starch) are effective at stabilizing emulsions containing relatively large oil droplets. Future research is encouraged to identify, isolate, purify, and characterize new types of natural emulsifier, and to test their efficacy in food, cosmetic, detergent, personal care, and other products. PMID- 27181393 TI - Applications of plant terpenoids in the synthesis of colloidal silver nanoparticles. AB - Green chemistry is the design of chemical products and processes that reduce or eliminate the generation of hazardous substances. Since the last few years, natural products especially plant secondary metabolites have been extensively explored for their potency to synthesize silver nanoparticles (AgNPs). The plant based AgNPs are safer, energy efficient, eco-friendly, and less toxic than chemically synthesized counterparts. The secondary metabolites, ubiquitously found in plants especially the terpenoid-rich essential oils, have a significant role in AgNPs synthesis. Terpenoids belong to the largest family of natural products and are found in all kinds of organisms. Their involvement in the synthesis of plant-based AgNPs has got much attention in the recent years. The current article is not meant to provide an exhaustive overview of green synthesis of nanoparticles, but to present the pertinent role of plant terpenoids in the biosynthesis of AgNPs, as capping and reducing agents for development of uniform size and shape AgNPs. An emphasis on the important role of FTIR in the identification and elucidation of major functional groups in terpenoids for AgNPs synthesis has also been reviewed in this manuscript. It was found that no such article is available that has discussed the role of plant terpenoids in the green synthesis of AgNPs. PMID- 27181394 TI - Role of family support and women's knowledge on pregnancy-related risks in adherence to maternal iron-folic acid supplementation in Indonesia. AB - OBJECTIVE: To examine whether women's knowledge of pregnancy-related risks and family support received during pregnancy are associated with adherence to maternal iron-folic acid (IFA) supplementation. DESIGN: Secondary data analysis of the 2002-03, 2007 and 2012 Indonesia Demographic and Health Survey. Analysis of the association between factors associated with adherence (consuming >=90 IFA tablets), including the women's knowledge and family support, was performed using multivariate logistic regression. SETTING: National household survey. SUBJECTS: Women (n 19 133) who had given birth within 2 years prior to the interview date. RESULTS: Knowledge of pregnancy-related risks was associated with increased adherence to IFA supplementation (adjusted OR=1.8; 95 % CI 1.6, 2.0), as was full family (particularly husband's) support (adjusted OR=1.9; 95 % CI 1.6, 2.3). Adequate antenatal care (ANC) visits (i.e. four or more) was associated with increased adherence (adjusted OR=2.2; 95 % CI 2.0, 2.4). However, ANC providers missed opportunities to distribute tablets and information, as among women with adequate ANC visits, 15 % reported never having received/bought any IFA tablets and 30 % had no knowledge of pregnancy-related risks. A significant interaction was observed between family support and the women's educational level in predicting adherence. Family support significantly increased the adherence among women with <9 years of education. CONCLUSIONS: Improving women's knowledge of pregnancy-related risks and involving family members, particularly the husband and importantly for less-educated women, improved adherence to IFA supplementation. ANC visit opportunities must be optimized to provide women with sufficient numbers of IFA tablets along with health information (especially on pregnancy-related risks) and partner support counselling. PMID- 27181396 TI - Primitive red alga Cyanidioschyzon merolae accumulates storage glucan and triacylglycerol under nitrogen depletion. AB - Most microalgae accumulate neutral lipids, including triacylglycerol (TAG), into spherical structures called lipid bodies (LBs) under environmental stress conditions such as nutrient depletion. In green algae, starch accumulation precedes TAG accumulation, and the starch is thought to be a substrate for TAG synthesis. However, the relationship between TAG synthesis and the starch content in red algae, as well as how TAG accumulation is regulated, is unclear. In this study, we cultured the primitive red alga Cyanidioschyzon merolae under nitrogen depleted conditions, and monitored the formation of starch granules (SGs) and LBs using microscopy. SGs stained with potassium iodide were observed at 24 h; however, LBs stained specifically with BODIPY 493/503 were observed after 48 h. Quantitative analysis of neutral sugar and cytomorphological semi-quantitative analysis of TAG accumulation also supported these results. Thus, the accumulation of starch occurred and preceded the accumulation of TAG in cells of C. merolae. However, TAG accumulation was not accompanied by a decrease in the starch content, suggesting that the starch is a major carbon storage sink, at least under nitrogen-depleted conditions. Quantitative real-time PCR revealed that the mRNA levels of genes involved in starch and TAG synthesis rarely changed during the culture period, suggesting that starch and TAG synthesis in C. merolae are not controlled through gene transcription but at other stages, such as translation and/or enzymatic activity. PMID- 27181395 TI - Detection of the Previously Unobserved Stereoisomers of Thujone in the Essential Oil and Consumable Products of Sage (Salvia officinalis L.) Using Headspace Solid Phase Microextraction-Gas Chromatography-Mass Spectrometry. AB - The discovery of the (+)-alpha-thujone and (-)-beta-thujone stereoisomers in the essential oil of sage (Salvia officinalis L.) and dietary supplements is documented for the first time. The detection was accomplished using a chiral resolution protocol of racemic alpha-/beta-thujone on headspace solid-phase microextraction-gas chromatography-mass spectrometry. Because the previously unreported stereoisomers, (+)-alpha-thujone and (-)-beta-thujone, are not commercially available, a three-step synthesis of racemic thujone from commercially available starting materials was developed. Thermolysis studies demonstrated that no racemization at the cyclopropane stereocenters occurs, corroborating that the detection is not an artifact from the hydrodistillation process. The developed chiral resolution of thujone was also used to provide evidence for the absence of the (+)-alpha-thujone and (-)-beta-thujone enantiomers in other common thujone-containing essential oils. PMID- 27181398 TI - Interventions for Varicose Veins: Beyond Ablation. AB - OPINION STATEMENT: Minimally invasive endothermal treatments have replaced surgical ligation and stripping in the management of chronic venous insufficiency (CVI) and are now considered the standard of care. Newer techniques have emerged in the last few years in an attempt to further minimize the procedural discomfort associated with endothermal procedures. These new techniques are designed to avoid tumescent anesthesia (TA). These new non-thermal, tumescentless techniques are well tolerated and are shown to result in equivalent outcomes when compared to the thermal ablations. Since there is no data to support the argument that one of these therapies is truly superior to another, selection of a particular thermal or non-thermal technique is dependent on patient and physician preferences. Adoption of a particular non-thermal procedure is also dependent on other factors such as the learning curve, initial setup costs, overall cost effectiveness and reimbursement. Once the reimbursement issues are resolved and durability is confirmed, these techniques have the potential to become the new standard of care for the management of CVI. PMID- 27181397 TI - Medical Therapy in Peripheral Artery Disease and Critical Limb Ischemia. AB - OPINION STATEMENT: Peripheral artery disease (PAD) comprises atherosclerosis of the aorta and lower extremities. Many patients with PAD are asymptomatic, while others present with intermittent claudication (IC) or critical limb ischemia (CLI). Defined as rest pain or tissue loss that persists for >2 weeks, CLI represents the most severe clinical manifestation of PAD and is associated with an increased risk of limb loss and death. Patients with PAD, including those with CLI, are underdiagnosed and undertreated. In addition to smoking cessation, medical therapy with an antiplatelet agent and statin is recommended for all patients with PAD. Regular exercise has been shown to improve walking distance and quality of life in patients with symptomatic PAD and should be incorporated into each patient's treatment plan. In patients who have CLI and in those with persistent lifestyle-limiting claudication despite optimal medical therapy and an exercise program, revascularization is indicated for limb salvage and symptom relief, respectively. Consensus guidelines currently support an endovascular first approach to revascularization in the majority of cases. Surgical procedures provide an alternative to endovascular therapy in select cases. PMID- 27181400 TI - Cardiovascular Complications of Cranial and Neck Radiation. AB - OPINION STATEMENT: Cancer survivors who receive head and neck radiation are at increased risk for cerebrovascular events. This is mediated via damage to the hypothalamus-pituitary axis leading to the metabolic syndrome and extracranial arterial injury leading to carotid artery stenosis. Head and neck radiation can also lead to intracranial injury that can present as moyamoya, especially in children. Survivors require lifelong periodic follow-up for the development of pan-hypopituitarism or its individual components as well as for dyslipidemia and obesity. Aggressive control of traditional cardiovascular risk factors is recommended to reduce cardiovascular morbidity and mortality. There are no specific guidelines for the surveillance and management of asymptomatic carotid artery disease in cancer survivors. However, regular detailed examination for carotid bruits and neurological symptoms is recommended. Treatment of significant radiation-induced carotid artery disease has not been specifically studied and is based upon recommendations for patients with atherosclerotic carotid stenosis. Carotid endarterectomy can be difficult in radiation patients due to anatomic concerns and the risk of post-operative cranial nerve injury and wound complications but should be considered in patients with suitable anatomy and neck architecture. Carotid artery stenting, while successful, may be associated with greater long-term mortality and neurologic complications. Regardless of the strategy employed, radiation patients are at increased risk for restenosis and should undergo routine surveillance even after revascularization. PMID- 27181399 TI - Exercise and Aerobic Fitness to Reduce Cancer-Related Cardiovascular Toxicity. AB - OPINION STATEMENT: Several cancer treatments are associated with vascular toxicity, mainly mediated by their effects on endothelial cell function. In turn, vascular dysfunction may contribute to cardiac damage and other cardiovascular side effects such as hypertension, stroke, and arterial and venous thrombosis. Aerobic exercise is associated with numerous beneficial effects on the endothelium and on cardiovascular risk factors, and may potentially modulate some of the mechanisms of vascular damage associated with antineoplastic therapies, thereby reducing their cardiovascular toxicity. To date, only a very limited number of studies have focused on the effects of supervised exercise on endothelial function in cancer patients undergoing treatment and molecular mechanisms remain to be explored. Further mechanistic, translational, and clinical research is needed to investigate the potential protective role of exercise on the vascular toxicity of cancer treatments. PMID- 27181402 TI - Differentiation of Isomeric Ginsenosides by Using Electron-Induced Dissociation Mass Spectrometry. AB - Current phytochemical research on ginsengs focuses on the structural characterization and isomer differentiation of ginsenosides. In this Letter, electron-induced dissociation (EID) was initially investigated by analyzing isomeric ginsenosides. EID provided more structural information on their differentiation than collision-induced dissociation (CID) did. Glycosyl group migration previously observed in the CID of oligosaccharide ions could also be found in the EID of protonated Rg1. This rearrangement reaction would show substantial ambiguities in differentiating Rg1 from Rf. Although other charge carriers could alleviate this problem, the use of EID in dissociating deprotonated ginsenoside ions was superior to other techniques in terms of eliminating glycosyl group migration and generating diagnostic fragment ions for the differentiation of structural isomers. This study demonstrates a potential method to analyze natural products and thus help discover and evaluate novel compounds. PMID- 27181401 TI - Use of Noninvasive Imaging in Cardiac Amyloidosis. AB - OPINION STATEMENT: Cardiac involvement in amyloidosis is associated with poor outcomes. The standard test for the diagnosis of cardiac amyloidosis is endomyocardial biopsy but given current advances in noninvasive imaging, the diagnosis is frequently obtained or strongly suspected without biopsy. Echocardiography is the most utilized cardiac imaging modality, particularly myocardial strain measures with this modality have been found to be a predictor of clinical outcomes, superior to traditional parameters. Other known imaging modalities with new, useful protocols for this pathology include nuclear imaging and cardiac magnetic resonance (CMR). In particular, CMR has excellent sensitivity and specificity. PMID- 27181403 TI - Divergent Inflammatory, Fibrogenic, and Liver Progenitor Cell Dynamics in Two Common Mouse Models of Chronic Liver Injury. AB - Complications of end-stage chronic liver disease signify a major cause of mortality worldwide. Irrespective of the underlying cause, most chronic liver diseases are characterized by hepatocellular necrosis, inflammation, fibrosis, and proliferation of liver progenitor cells or ductular reactions. Vast differences exist between experimental models that mimic these processes, and their identification is fundamental for translational research. We compared two common murine models of chronic liver disease: the choline-deficient, ethionine supplemented (CDE) diet versus thioacetamide (TAA) supplementation. Markers of liver injury, including serum alanine transaminase levels, apoptosis, hepatic fat loading, and oxidative stress, as well as inflammatory, fibrogenic and liver progenitor cell responses, were assessed at days 3, 7, 14, 21, and 42. This study revealed remarkable differences between the models. It identified periportal injury and fibrosis with an early peak and slow normalization of all parameters in the CDE regimen, whereas TAA-treated mice had pericentral patterns of progressive injury and fibrosis, resulting in a more severe hepatic injury phenotype. This study is the first to resolve two different patterns of injury and fibrosis in the CDE and TAA model and to indisputably identify the fibrosis pattern in the TAA model as driven from the pericentral vein region. Our data provide a valuable foundation for future work using the CDE and TAA regimens to model a variety of human chronic liver diseases. PMID- 27181405 TI - Intrahepatic Xenograft of Cutaneous T-Cell Lymphoma Cell Lines: A Useful Model for Rapid Biological and Therapeutic Evaluation. AB - Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of diseases primarily involving the skin that could have an aggressive course with circulating blood cells, especially in Sezary syndrome and transformed mycosis fungoides. So far, few CTCL cell lines have been adapted for in vivo experiments and their tumorigenicity has not been adequately assessed, hampering the use of a reproducible model for CTCL biological evaluation. In fact, both patient-derived xenografts and cell line xenografts at subcutaneous sites failed to provide a robust tool, because engraftment was dependent on mice strain and cell line subtype. Herein, we describe an original method of intrahepatic injection into adult NOD.Cg-Prkdc(scid)Il2rg(tm1Wjl)/SzJ mice liver of both aggressive (My-La, HUT78, HH, MAC2A, and MAC2B) and indolent (FE-PD and MAC1) CTCL cell lines. Six of the seven CTCL cell lines were grafted with a high rate of success (80%). Moreover, this model provided a quick (15 days) and robust assay for in vivo evaluation of CTCL cell lines tumorigenicity and therapeutic response in preclinical studies. Such a reproducible model can be therefore used for further functional studies and in vivo drug testing. PMID- 27181404 TI - PERK Activation Promotes Medulloblastoma Tumorigenesis by Attenuating Premalignant Granule Cell Precursor Apoptosis. AB - Evidence suggests that activation of pancreatic endoplasmic reticulum kinase (PERK) signaling in response to endoplasmic reticulum stress negatively or positively influences cell transformation by regulating apoptosis. Patched1 heterozygous deficient (Ptch1(+/-)) mice reproduce human Gorlin's syndrome and are regarded as the best animal model to study tumorigenesis of the sonic hedgehog subgroup of medulloblastomas. It is believed that medulloblastomas in Ptch1(+/-) mice results from the transformation of granule cell precursors (GCPs) in the developing cerebellum. Here, we determined the role of PERK signaling on medulloblastoma tumorigenesis by assessing its effects on premalignant GCPs and tumor cells. We found that PERK signaling was activated in both premalignant GCPs in young Ptch1(+/-) mice and medulloblastoma cells in adult mice. We demonstrated that PERK haploinsufficiency reduced the incidence of medulloblastomas in Ptch1(+/-) mice. Interestingly, PERK haploinsufficiency enhanced apoptosis of premalignant GCPs in young Ptch1(+/-) mice but had no significant effect on medulloblastoma cells in adult mice. Moreover, we showed that the PERK pathway was activated in medulloblastomas in humans. These results suggest that PERK signaling promotes medulloblastoma tumorigenesis by attenuating apoptosis of premalignant GCPs during the course of malignant transformation. PMID- 27181407 TI - Validation of the NCCN-IPI in both de novo and transformed diffuse large B cell lymphoma. PMID- 27181406 TI - Epithelial-Derived Inflammation Disrupts Elastin Assembly and Alters Saccular Stage Lung Development. AB - The highly orchestrated interactions between the epithelium and mesenchyme required for normal lung development can be disrupted by perinatal inflammation in preterm infants, although the mechanisms are incompletely understood. We used transgenic (inhibitory kappaB kinase beta transactivated) mice that conditionally express an activator of the NF-kappaB pathway in airway epithelium to investigate the impact of epithelial-derived inflammation during lung development. Epithelial NF-kappaB activation selectively impaired saccular stage lung development, with a phenotype comprising rapidly progressive distal airspace dilation, impaired gas exchange, and perinatal lethality. Epithelial-derived inflammation resulted in disrupted elastic fiber organization and down-regulation of elastin assembly components, including fibulins 4 and 5, lysyl oxidase like-1, and fibrillin-1. Fibulin-5 expression by saccular stage lung fibroblasts was consistently inhibited by treatment with bronchoalveolar lavage fluid from inhibitory kappaB kinase beta transactivated mice, Escherichia coli lipopolysaccharide, or tracheal aspirates from preterm infants exposed to chorioamnionitis. Expression of a dominant NF-kappaB inhibitor in fibroblasts restored fibulin-5 expression after lipopolysaccharide treatment, whereas reconstitution of fibulin-5 rescued extracellular elastin assembly by saccular stage lung fibroblasts. Elastin organization was disrupted in saccular stage lungs of preterm infants exposed to systemic inflammation. Our study reveals a critical window for elastin assembly during the saccular stage that is disrupted by inflammatory signaling and could be amenable to interventions that restore elastic fiber assembly in the developing lung. PMID- 27181410 TI - Developmental plasticity of phrenic motoneuron and diaphragm properties with the inception of inspiratory drive transmission in utero. AB - The review outlines data consistent with the hypothesis that inspiratory drive transmission that generates fetal breathing movements (FBMs) is essential for the developmental plasticity of phrenic motoneurons (PMNs) and diaphragm musculature prior to birth. A systematic examination during the perinatal period demonstrated a very marked transformation of PMN and diaphragm properties coinciding with the onset and strengthening of inspiratory drive and FBMs in utero. This included studies of age-dependent changes of: i) morphology, neuronal coupling, passive and electrophysiological properties of PMNs; ii) rhythmic inspiratory activity in vitro; iii) FBMs generated in vivo detected by ultrasonography; iv) contractile and end-plate potential properties of diaphragm musculature. We also propose how the hypothesis can be further evaluated with studies of perinatal hypoglossal motoneuron-tongue musculature and the use of Dbx1 null mice that provide an experimental model lacking descending inspiratory drive transmission in utero. PMID- 27181409 TI - A single exercise bout enhances the manufacture of viral-specific T-cells from healthy donors: implications for allogeneic adoptive transfer immunotherapy. AB - Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections remain a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). The adoptive transfer of donor-derived viral-specific cytotoxic T-cells (VSTs) is an effective treatment for controlling CMV and EBV infections after HSCT; however, new practical methods are required to augment the ex vivo manufacture of multi-VSTs from healthy donors. This study investigated the effects of a single exercise bout on the ex vivo manufacture of multi-VSTs. PBMCs isolated from healthy CMV/EBV seropositive participants before (PRE) and immediately after (POST) 30-minutes of cycling exercise were stimulated with CMV (pp65 and IE1) and EBV (LMP2A and BMLF1) peptides and expanded over 8 days. The number (fold difference from PRE) of T-cells specific for CMV pp65 (2.6), EBV LMP2A (2.5), and EBV BMLF1 (4.4) was greater among the VSTs expanded POST. VSTs expanded PRE and POST had similar phenotype characteristics and were equally capable of MHC-restricted killing of autologous target cells. We conclude that a single exercise bout enhances the manufacture of multi-VSTs from healthy donors without altering their phenotype or function and may serve as a simple and economical adjuvant to boost the production of multi-VSTs for allogeneic adoptive transfer immunotherapy. PMID- 27181408 TI - Time trends in the aetiology of prosthetic joint infections: a multicentre cohort study. AB - It is important to know the spectrum of the microbial aetiology of prosthetic joint infections (PJIs) to guide empiric treatment and establish antimicrobial prophylaxis in joint replacements. There are no available data based on large contemporary patient cohorts. We sought to characterize the causative pathogens of PJIs and to evaluate trends in the microbial aetiology. We hypothesized that the frequency of antimicrobial-resistant organisms in PJIs has increased in the recent years. We performed a cohort study in 19 hospitals in Spain, from 2003 to 2012. For each 2-year period (2003-2004 to 2011-2012), the incidence of microorganisms causing PJIs and multidrug-resistant bacteria was assessed. Temporal trends over the study period were evaluated. We included 2524 consecutive adult patients with a diagnosis of PJI. A microbiological diagnosis was obtained for 2288 cases (90.6%). Staphylococci were the most common cause of infection (1492, 65.2%). However, a statistically significant rising linear trend was observed for the proportion of infections caused by Gram-negative bacilli, mainly due to the increase in the last 2-year period (25% in 2003-2004, 33.3% in 2011-2012; p 0.024 for trend). No particular species contributed disproportionally to this overall increase. The percentage of multidrug-resistant bacteria PJIs increased from 9.3% in 2003-2004 to 15.8% in 2011-2012 (p 0.008), mainly because of the significant rise in multidrug-resistant Gram-negative bacilli (from 5.3% in 2003-2004 to 8.2% in 2011-2012; p 0.032). The observed trends have important implications for the management of PJIs and prophylaxis in joint replacements. PMID- 27181412 TI - Electrical stimulation of the vmPFC serves as a remote control to affect VTA activity and improve depressive-like behavior. AB - Despite progress in elucidating mechanisms of depression, the efficacy of different treatments remains inadequate. Recent small-scale clinical studies suggested anti-depressant treatment using deep brain stimulation (DBS) of the ventral capsule/ventral striatum or subgenual cingulate cortex (SCC), yet controlled, multi-center trials were unsuccessful. We recently suggested the ventral tegmental area (VTA) as an important intersection for treating depression. We also found that stimulation of the VTA of a genetic rat model of depression (Flinders Sensitive Line (FSL) rats) with a programmed pattern designed to mimic the burst firing of normal rats decreases depressive-like behavior. Herein, we examined the possibility of reaching the VTA - located deep in the brain stem - through its direct connection to the ventro-medial prefrontal cortex (vmPFC), which parallels the human SCC. Thus, we compared treatment of FSLs with modified versions of DBS - either chronic-intermittent low-frequency electrical stimulation of the vmPFC, or patterned acute electrical stimulation (pAES), which integrates transcranial magnetic stimulation properties, namely, bursts of pulse trains and low frequency stimulation, applied to the VTA. We found that stimulation of the vmPFC (20Hz, 15min/day, 10days) improved depressive like behavior and VTA local field potential (LFP) activity of FSLs, yet it had only a partial long-term effect on behavior. In particular, vmPFC stimulation decreased theta band activity, which correlated with the improvement in depressive-like behavior of all treated FSLs at day 1, and in ~50% of treated FSLs at day 28 post treatment. pAES of the VTA (10Hz, 20min) caused significant, long-term improvement of depressive-like behavior of FSLs, concurrently with normalizing intra-VTA LFP activity, and increasing VTA LFP synchronicity and hippocampal BDNF mRNA levels. Thus, although low-frequency electrical stimulation of the PFC alters VTA activity, leading to attenuation of depressive-like manifestations, a specific stimulation pattern affecting VTA cell programming is important for long-term efficacy. PMID- 27181411 TI - Neonatal seizures induced by pentylenetetrazol or kainic acid disrupt primary cilia growth on developing mouse cortical neurons. AB - Neonatal or early-life seizures (ELS) are often associated with life-long neurophysiological, cognitive and behavioral deficits, but the underlying mechanisms contributing to these deficits remain poorly understood. Newborn, post migratory cortical neurons sprout ciliary buds (procilia) that mature into primary cilia. Disruption of the growth or signaling capabilities of these cilia has been linked to atypical neurite outgrowth from neurons and abnormalities in neuronal circuitry. Here, we tested the hypothesis that generalized seizures induced by pentylenetetrazol (PTZ) or kainic acid (KA) during early postnatal development impair neuronal and/or glial ciliogenesis. Mice received PTZ (50 or 100mg/kg), KA (2mg/kg), or saline either once at birth (P0), or once daily from P0 to P4. Using immunohistochemistry and electron microscopy, the cilia of neurons and glia were examined at P7, P14, and P42. A total of 83 regions were analyzed, representing 13 unique neocortical and hippocampal regions. Neuronal cilia were identified by co-expression of NeuN and type 3 adenylyl cyclase (ACIII) or somatostatin receptor 3 (SSTR3), while glial cilia were identified by co-expression of GFAP, Arl13b, and gamma-tubulin. We found that PTZ exposure at either P0 or from P0 to P4 induced convulsive behavior, followed by acute and lasting effects on neuronal cilia lengths that varied depending on the cortical region, PTZ dose, injection frequency, and time post-PTZ. Both increases and decreases in neuronal cilia length were observed. No changes in the length of glial cilia were observed under any of the test conditions. Lastly, we found that a single KA seizure at P0 led to similar abnormalities in neuronal cilia lengths. Our results suggest that seizure(s) occurring during early stages of cortical development induce persistent and widespread changes in neuronal cilia length. Given the impact neuronal cilia have on neuronal differentiation, ELS-induced changes in ciliogenesis may contribute to long-term pathology and abnormal cortical function. PMID- 27181413 TI - Sensitization to the locomotor stimulant effects of "bath salt" constituents, 4 methylmethcathinone (4-MMC) and 3,4-methylenedioxypyrovalerone (MDPV), in male Sprague-Dawley rats. AB - BACKGROUND: Synthetic cathinones, 4-methylmethcathinone (4-MMC) and 3,4 methylenedioxypyrovalerone (MDPV), serve as a substrate or blocker at monoaminergic transporters, respectively, and produce locomotor stimulant effects in rodents. The present study investigated in rats the effects of repeated exposure to 4-MMC, MDPV, or mixtures of the two on the induction of locomotor sensitization and expression of cross-sensitization to cocaine. METHODS: Seventy two male Sprague-Dawley rats received daily intraperitoneal injections of saline, MDPV (0.5mg/kg), 4-MMC (0.5, 1.0, or 2.0mg/kg) or mixtures of 0.5mg/kg MDPV+4-MMC (0.5, 1.0, or 2.0mg/kg) for seven consecutive days. Locomotor activity was recorded on days 1 and 7 and again after an acute injection of 5mg/kg cocaine following a 10day drug washout period. RESULTS: Rats injected with 0.5mg/kg MDPV, 0.5, 1.0, or 2.0mg/kg 4-MMC, or 2.0mg/kg 4-MMC+0.5mg/kg MDPV displayed time dependent increases in horizontal activity that were augmented on day 7 compared to day 1. In addition, rats pretreated with 0.5mg/kg MDPV, 2.0mg/kg 4-MMC, or mixtures of 4-MMC+MDPV displayed an enhanced response to cocaine. CONCLUSIONS: Locomotor responses sensitize to MDPV and to certain mixtures of MDPV and 4-MMC following repeated dosing. Furthermore, previous exposure to these substances may produce cross-sensitization to the locomotor stimulant effects of cocaine. Considered together with recent findings that 4-MMC and MDPV have different sites of action, but both influence monoaminergic functioning, further investigations utilizing a variety of behavioral assays may prove informative regarding the abuse liability of synthetic cathinone mixtures. PMID- 27181415 TI - The recollective qualities of adolescents' and adults' narratives about a long ago tornado. AB - The recollective qualities of autobiographical memory are thought to develop over the course of the first two decades of life. We used a 9-year follow-up test of recall of a devastating tornado and of non-tornado-related events from before and after the storm, to compare the recollective qualities of adolescents' (n = 20, ages 11 years, 11 months to 20 years, 8 months) and adults' (n = 14) autobiographical memories. At the time of the tornado, half of the adolescents had been younger than age 6. Nine years after the event, all participants provided evidence that they recall the event of the tornado. Adults also had high levels of recall of the non-tornado-related events. Adolescents recalled proportionally fewer non-tornado-related events; adolescents younger than 6 at the time of the events recalled the fewest non-tornado-related events. Relative to adolescents, adults produced longer narratives. With narrative length controlled, there were few differences in the recollective qualities of adolescents' and adults' narrative reports, especially in the case of the tornado; the recollective qualities were stronger among adolescents older at the time of the events. Overall, participants in both age groups provided evidence of the qualities of recollection that are characteristic of autobiographical memory. PMID- 27181416 TI - Letter to the Editor: Comparison of cognitive functions, pre-morbid conditions and clinical characteristics between brief psychotic disorder and schizophrenia. PMID- 27181414 TI - Diabetic complications within the context of aging: Nicotinamide adenine dinucleotide redox, insulin C-peptide, sirtuin 1-liver kinase B1-adenosine monophosphate-activated protein kinase positive feedback and forkhead box O3. AB - Recent research in nutritional control of aging suggests that cytosolic increases in the reduced form of nicotinamide adenine dinucleotide and decreasing nicotinamide adenine dinucleotide metabolism plays a central role in controlling the longevity gene products sirtuin 1 (SIRT1), adenosine monophosphate-activated protein kinase (AMPK) and forkhead box O3 (FOXO3). High nutrition conditions, such as the diabetic milieu, increase the ratio of reduced to oxidized forms of cytosolic nicotinamide adenine dinucleotide through cascades including the polyol pathway. This redox change is associated with insulin resistance and the development of diabetic complications, and might be counteracted by insulin C peptide. My research and others' suggest that the SIRT1-liver kinase B1-AMPK cascade creates positive feedback through nicotinamide adenine dinucleotide synthesis to help cells cope with metabolic stress. SIRT1 and AMPK can upregulate liver kinase B1 and FOXO3, key factors that help residential stem cells cope with oxidative stress. FOXO3 directly changes epigenetics around transcription start sites, maintaining the health of stem cells. 'Diabetic memory' is likely a result of epigenetic changes caused by high nutritional conditions, which disturb the quiescent state of residential stem cells and impair tissue repair. This could be prevented by restoring SIRT1-AMPK positive feedback through activating FOXO3. PMID- 27181417 TI - Organelle remodeling at membrane contact sites. AB - Cellular organelles must execute sophisticated biological processes to persist, and often communicate with one another to exchange metabolites and information. Recent studies suggest inter-organelle membrane contact sites (MCSs) are hubs for this cellular cross-talk. MCSs also govern membrane remodeling, thus controlling aspects of organelle shape, identity, and function. Here, we summarize three emerging phenomena that MCSs appear to govern: 1) organelle identity via the non vesicular exchange of lipids, 2) mitochondrial shape and division, and 3) endosomal migration in response to sterol trafficking. We also discuss the role for ER-endolysosomal contact sites in cholesterol metabolism, and the potential biomedical importance this holds. Indeed, the emerging field inter-organellar cross-talk promises substantial advances in the fields of lipid metabolism and cell signaling. PMID- 27181418 TI - The unexpected structure of the designed protein Octarellin V.1 forms a challenge for protein structure prediction tools. AB - Despite impressive successes in protein design, designing a well-folded protein of more 100 amino acids de novo remains a formidable challenge. Exploiting the promising biophysical features of the artificial protein Octarellin V, we improved this protein by directed evolution, thus creating a more stable and soluble protein: Octarellin V.1. Next, we obtained crystals of Octarellin V.1 in complex with crystallization chaperons and determined the tertiary structure. The experimental structure of Octarellin V.1 differs from its in silico design: the (alphabetaalpha) sandwich architecture bears some resemblance to a Rossman-like fold instead of the intended TIM-barrel fold. This surprising result gave us a unique and attractive opportunity to test the state of the art in protein structure prediction, using this artificial protein free of any natural selection. We tested 13 automated webservers for protein structure prediction and found none of them to predict the actual structure. More than 50% of them predicted a TIM-barrel fold, i.e. the structure we set out to design more than 10years ago. In addition, local software runs that are human operated can sample a structure similar to the experimental one but fail in selecting it, suggesting that the scoring and ranking functions should be improved. We propose that artificial proteins could be used as tools to test the accuracy of protein structure prediction algorithms, because their lack of evolutionary pressure and unique sequences features. PMID- 27181419 TI - Graphene-clad microfibre saturable absorber for ultrafast fibre lasers. AB - Graphene, whose absorbance is approximately independent of wavelength, allows broadband light-matter interactions with ultrafast responses. The interband optical absorption of graphene can be saturated readily under strong excitation, thereby enabling scientists to exploit the photonic properties of graphene to realize ultrafast lasers. The evanescent field interaction scheme of the propagating light with graphene covered on a D-shaped fibre or microfibre has been employed extensively because of the nonblocking configuration. Obviously, most of the fibre surface is unused in these techniques. Here, we exploit a graphene-clad microfibre (GCM) saturable absorber in a mode-locked fibre laser for the generation of ultrafast pulses. The proposed all-surface technique can guarantee a higher efficiency of light-graphene interactions than the aforementioned techniques. Our GCM-based saturable absorber can generate ultrafast optical pulses within 1.5 MUm. This saturable absorber is compatible with current fibre lasers and has many merits such as low saturation intensities, ultrafast recovery times, and wide wavelength ranges. The proposed saturable absorber will pave the way for graphene-based wideband photonics. PMID- 27181420 TI - Smooth and flat phase-locked Kerr frequency comb generation by higher order mode suppression. AB - High-Q microresonator is perceived as a promising platform for optical frequency comb generation, via dissipative soliton formation. In order to achieve a higher quality factor and obtain the necessary anomalous dispersion, multi-mode waveguides were previously implemented in Si3N4 microresonators. However, coupling between different transverse mode families in multi-mode waveguides results in periodic disruption of dispersion and quality factor, and consequently causes perturbation to dissipative soliton formation and amplitude modulation to the corresponding spectrum. Careful choice of pump wavelength to avoid the mode crossing region is thus critical in conventional Si3N4 microresonators. Here, we report a novel design of Si3N4 microresonator in which single-mode operation, high quality factor, and anomalous dispersion are attained simultaneously. The novel microresonator is consisted of uniform single-mode waveguides in the semi circle region, to eliminate bending induced mode coupling, and adiabatically tapered waveguides in the straight region, to avoid excitation of higher order modes. The intrinsic quality factor of the microresonator reaches 1.36 * 10(6) while the group velocity dispersion remains to be anomalous at -50 fs(2)/mm. With this novel microresonator, we demonstrate that broadband phase-locked Kerr frequency combs with flat and smooth spectra can be generated by pumping at any resonances in the optical C-band. PMID- 27181421 TI - Locating Organic Guests in Inorganic Host Materials from X-ray Powder Diffraction Data. AB - Can the location of the organic structure-directing agent (SDA) inside the channel system of a zeolite be determined experimentally in a systematic manner? In an attempt to answer this question, we investigated six borosilicate zeolites of known framework structure (SSZ-53, SSZ-55, SSZ-56, SSZ-58, SSZ-59, and SSZ 60), where the location of the SDA had only been simulated using molecular modeling techniques in previous studies. From synchrotron powder diffraction data, we were able to retrieve reliable experimental positions for the SDA by using a combination of simulated annealing (global optimization) and Rietveld refinement. In this way, problems arising from data quality and only partially compatible framework and SDA symmetries, which can lead to indecipherable electron density maps, can be overcome. Rietveld refinement using geometric restraints were then performed to optimize the positions and conformations of the SDAs. With these improved models, it was possible to go on to determine the location of the B atoms in the framework structure. That is, two pieces of information that are key to the understanding of zeolite synthesis-the location of the organic SDA in the channel system and of the positions adopted by heteroatoms in the silicate framework-can be extracted from experimental data using a systematic strategy. In most cases, the locations of the SDAs determined experimentally compare well with those simulated with molecular modeling, but there are also some clear differences, and the reason for these differences can be understood. The approach is generally applicable, and has also been used to locate organic guests, linkers, and ligands in metal-organic compounds. PMID- 27181423 TI - Nanoscale heterogeneity in thermoelectrics: the occurrence of phase separation in Fe-doped Ca3Co4O9. AB - The misfit layered cobaltate thermoelectrics are good candidates for high temperature thermoelectric applications. Ca3Co4O9 is a typical compound of this family, which consists of rock salt Ca2CoO3 slabs alternating with hexagonal CoO2 slabs with a large lattice mismatch along the b axis. Each slab is 0.3-0.5 nm thick and shows an inherent structural heterogeneity at the nanoscale. The latter is a key parameter that affects the electrical transport and the heat flow in these misfit structured thermoelectrics. To clarify the physical origin of the thermoelectric performance of iron doped Ca3Co4O9 we combined X-ray near-edge absorption spectroscopy (XANES) and quantum modeling using density functional theory. In contrast to single-site doping, the iron doping first occurs at the Co1 site of the rock salt slab at low doping while at higher doping it prefers the Ca1 site of the rock salt slab. Doping at the Ca1 site modifies the electronic structure tuning the nanoscale structural heterogeneity. This mechanism may open a new route to optimizing the thermoelectric performance of misfit layered thermoelectrics. PMID- 27181424 TI - Self-cleaning and antibiofouling enamel surface by slippery liquid-infused technique. AB - We aimed to create a slippery liquid-infused enamel surface with antibiofouling property to prevent dental biofilm/plaque formation. First, a micro/nanoporous enamel surface was obtained by 37% phosphoric acid etching. The surface was then functionalized by hydrophobic low-surface energy heptadecafluoro-1,1,2,2-tetra- hydrodecyltrichlorosilane. Subsequent infusion of fluorocarbon lubricants (Fluorinert FC-70) into the polyfluoroalkyl-silanized rough surface resulted in an enamel surface with slippery liquid-infused porous surface (SLIPS). The results of water contact angle measurement, diffuse-reflectance Fourier transform infrared spectroscopy, and atomic force microscope confirmed that the SLIPS was successfully constructed on the enamel surface. The antibiofouling property of the SLIPS was evaluated by the adsorption of salivary protein of mucin and Streptococcus mutans in vitro, as well as dental biofilm formation using a rabbit model in vivo. The results showed that the SLIPS on the enamel surface significantly inhibited mucin adhesion and S. mutans biofilm formation in vitro, and inhibited dental plaque formation in vivo. PMID- 27181422 TI - Efficacy and safety of dapagliflozin in addition to insulin therapy in Japanese patients with type 2 diabetes: Results of the interim analysis of 16-week double blind treatment period. AB - INTRODUCTION: Dapagliflozin treatment when added to insulin therapy in Japanese patients with type 2 diabetes remains to be evaluated. MATERIALS AND METHODS: This was a multicenter, randomized, double-blind, parallel-group, placebo controlled study to evaluate efficacy (at 16 weeks) and long-term safety (at 52 weeks) of dapagliflozin in addition to insulin therapy. The interim analysis was carried out at week 16 to assess the efficacy and safety profiles. The patients receiving insulin (n = 182) were randomized to either dapagliflozin 5 mg or a placebo at a 2:1 ratio. The primary efficacy end-point was the change in hemoglobin A1c (HbA1c) from baseline at week 16. RESULTS: Patients in the dapagliflozin group showed an adjusted decrease in HbA1c of -0.55% from baseline, whereas the placebo showed a marginal increase of 0.05%. The placebo-corrected mean change of HbA1c from baseline to week 16 in dapagliflozin was -0.60% (P < 0.0001). In addition, the placebo-corrected mean change of fasting plasma glucose and bodyweight from baseline to week 16 in the dapagliflozin group was -22.7 mg/dL (P < 0.0001) and -1.21 kg (P < 0.0001), respectively. The placebo-corrected mean daily insulin dose in the dapagliflozin group was numerically decreased (treatment difference: -0.72 IU/day; P = 0.0743). No major episodes or discontinuations as a result of hypoglycemia were reported during the study period. CONCLUSIONS: Dapagliflozin used as add-on treatment to insulin therapy showed significantly greater reduction of HbA1c, fasting plasma glucose and bodyweight without severe hypoglycemia compared with the placebo at week 16. These results show the clinical benefit of prescribing dapagliflozin for Japanese patients with insufficient glycemic control even with insulin therapy. PMID- 27181426 TI - Pattern of Injuries and Treatment Given to Victims of Rana Plaza Tragedy in a Level II Armed Forces Medical Facility in Bangladesh. AB - BACKGROUND: Rana Plaza building collapse is the worst industrial disaster of Bangladesh so far. The 9-storied structure collapsed suddenly on April 24, 2013, with more than 4000 people inside. Bangladesh Armed Forces played a key role in the massive rescue operations. METHODS: We conducted a cross-sectional study with 423 victims who were treated at a Combined Military Hospital to review the pattern of injuries and management provided. RESULTS: Middle-aged (35+/-12.75 years) females (68.32%) were the majority of the victims. Among the injured, 42.35% had soft tissue injury, 22.55% had abrasions, 18.79% had fractures, 3.75% had facial injuries, and 2.5% each had head and abdominal injuries. We treated the injured with various surgical approaches, such as soft tissue debridement (38.84%), fasciotomy (18.79%), amputation (3.75%), and other procedures. We had to refer 8.27% of the patients to different advanced centers. The mortality rate was 5.91%, including 1 volunteer rescuer. CONCLUSION: Pattern of injuries and modalities of management needed in an industrial disaster is a valuable experience which can be utilized in preparing to face disasters in the future and beyond. Death of a voluntary rescuer once again warrants the necessity of using a helmet and safety gear during any rescue operation. (Disaster Med Public Health Preparedness. 2017;11:21-24). PMID- 27181427 TI - Preparation of Porous Cellulose Beads via Introduction of Diamine Spacers. AB - The current work presents a synthesis route based on the reductive amination of 2,3-dialdehyde cellulose beads with diamines to render micrometer-sized beads with increased specific surface area (SSA) and porosity in the mesoporous range. Specifically, the influence of the reductive amination of 2,3-dialdehyde cellulose (DAC) using aliphatic and aromatic tethered mono- and diamines on bead microstructure was investigated. Aliphatic and aromatic tethered monoamines were found to have limited utility for producing porous beads whereas the introduction of diamines provided beads with a porous texture and an SSA increasing from <1 to >30 m(2)/g. Both aliphatic and aromatic diamines were found to be useful in producing porous beads having a pore size distribution range of 10 to 100 nm, as verified by N2 gas adsorption and mercury intrusion porosimetry analyses. The true density of the functionalized DAC beads decreased to an average of about 1.36 g/cm(3) as compared to 1.48 g/cm(3) for the unfunctionalized, fully oxidized DAC beads. The total porosity of the beads was, according to mercury porosimetry, in the range of 54-64%. Reductive amination with 1,7-diaminoheptane provided beads that were stable under alkaline conditions (1 M NaOH). It was concluded that the introduction of tethered diamines into DAC beads is a facile method for producing mesoporous beads. PMID- 27181435 TI - Corrigendum. PMID- 27181425 TI - Biological function derived from predicted structures in CASP11. AB - In CASP11, the organizers sought to bring the biological inferences from predicted structures to the fore. To accomplish this, we assessed the models for their ability to perform quantifiable tasks related to biological function. First, for 10 targets that were probable homodimers, we measured the accuracy of docking the models into homodimers as a function of GDT-TS of the monomers, which produced characteristic L-shaped plots. At low GDT-TS, none of the models could be docked correctly as homodimers. Above GDT-TS of ~60%, some models formed correct homodimers in one of the largest docked clusters, while many other models at the same values of GDT-TS did not. Docking was more successful when many of the templates shared the same homodimer. Second, we docked a ligand from an experimental structure into each of the models of one of the targets. Docking to the models with two different programs produced poor ligand RMSDs with the experimental structure. Measures that evaluated similarity of contacts were reasonable for some of the models, although there was not a significant correlation with model accuracy. Finally, we assessed whether models would be useful in predicting the phenotypes of missense mutations in three human targets by comparing features calculated from the models with those calculated from the experimental structures. The models were successful in reproducing accessible surface areas but there was little correlation of model accuracy with calculation of FoldX evaluation of the change in free energy between the wild-type and the mutant. Proteins 2016; 84(Suppl 1):370-391. (c) 2016 Wiley Periodicals, Inc. PMID- 27181437 TI - Bronsted Acid-Catalyzed Transfer Hydrogenation of Imines and Alkenes Using Cyclohexa-1,4-dienes as Dihydrogen Surrogates. AB - Cyclohexa-1,4-dienes are introduced to Bronsted acid-catalyzed transfer hydrogenation as an alternative to the widely used Hantzsch dihydropyridines. While these hydrocarbon-based dihydrogen surrogates do offer little advantage over established protocols in imine reduction as well as reductive amination, their use enables the previously unprecedented transfer hydrogenation of structurally and electronically unbiased 1,1-di- and trisubstituted alkenes. The mild procedure requires 5.0 mol % of Tf2NH, but the less acidic sulfonic acids TfOH and TsOH work equally well. PMID- 27181428 TI - Low osteocalcin level is a risk factor for impaired glucose metabolism in a Chinese male population. AB - AIMS/INTRODUCTION: This study was to assess the association between serum osteocalcin level and glucose metabolism in a Chinese male population. MATERIALS AND METHODS: We carried out a cross-sectional study with a cohort of participants from the Fangchenggang Area Male Health and Examination Survey. The cross sectional study was carried out among 2,353 men, including 2,139 participants with normal glucose tolerance, 148 with impaired fasting glucose and 66 with type 2 diabetes. A subsample of 1,109 men with measurement of osteocalcin was observed in the cohort. After a 4-year follow-up period, 1,049 non-diabetic and 983 participants with normal glucose tolerance who submitted the available information were enrolled in the cohort. Participants were divided into group-H (>=23.33 ng/mL) and group-L (<23.33 ng/mL) by osteocalcin level. RESULTS: In the cross-sectional study, osteocalcin levels were highest in participants with normal glucose tolerance, followed by those with impaired fasting glucose and type 2 diabetes (P < 0.001). In partial correlation analysis adjusted for age, serum osteocalcin level was related to glucose level (r = -0.082, P < 0.001), insulin level (r = -0.079, P < 0.001) and insulin resistance (r = -0.065, P = 0.002). Compared with group-H, group-L was associated with an increased risk of type 2 diabetes (odds ratio 2.107, 95% confidence interval 1.123-3.955), impaired fasting glucose (odds ratio 2.106; 95% CI 1.528-2.902), and insulin resistance (odds ratio 1.359, 95% confidence interval 1.080-1.710) adjusted for age, education levels, cigarette smoking and lipid profiles. In the cohort study, the increased risk of impaired fasting glucose was significant in group-L vs group-H (3.3% vs 1.2%, P = 0.026). CONCLUSIONS: Low serum osteocalcin level was a risk factor for impaired glucose metabolism and subsequent type 2 diabetes. PMID- 27181436 TI - Pirfenidone inhibits the proliferation of fibroblasts from patients with active Crohn's disease. AB - OBJECTIVE: One-third of Crohn's disease (CD) patients develop intestinal strictures that require repeated surgical intervention. Current anti-inflammatory therapies have limited effect on stricture development, which necessitates the exploration of new pharmacological approaches. Pirfenidone (PFD), a novel anti fibrotic agent, was recently approved in Europe for the treatment of idiopathic pulmonary fibrosis (IPF). We hypothesized that observations in IPF could be transferable to intestinal fibrosis and that PFD inhibits the proliferation and extracellular matrix (ECM) turnover of gut-derived fibroblasts from CD patients. MATERIAL AND METHODS: Fibroblasts were isolated from biopsies of inflamed (n = 8) and non-inflamed (n = 5) colonic mucosa. Expression of CD90 and alpha-smooth muscle actin (alphaSMA) expression was determined by flow cytometry. The fibroblasts were cultured with PFD (0.5, 1.0 and 2.0 mg/ml). Proliferation was evaluated with CellTiter 96((r)) AQueous One Solution Cell Proliferation Assay. Production of matrix metalloproteinase-3 (MMP-3), tissue inhibitor of metalloproteinases-1 (TIMP-1) and collagen were assessed using ELISA and calorimetric assays, respectively. RESULTS: The majority of the fibroblasts were alphaSMA-positive myofibroblasts. PFD inhibited fibroblast proliferation [0.94 (PFD 0.5 mg/ml); 0.76 (1.0 mg/ml); 0.58 (2.0 mg/ml)] and production of MMP-3 [0.85 (0.5 mg/ml); 0.74 (1.0 mg/ml); 0.63 (2.0 mg/ml)] dose-dependently (both p = 0.0001). The anti-proliferative effect of PFD was reversible (p = 0.0001), indicating that PFD does not act by an irreversible cytotoxic mechanism. PFD did not influence neither TIMP-1 nor collagen production. CONCLUSION: PFD inhibited the proliferation and the production of MMP-3 dose-dependently in gut-derived fibroblast from CD patients. Our observations support further studies on PFD in stricturing CD. PMID- 27181438 TI - Probe-SAXS on hydrogels under elongation. AB - We have investigated the effect of polymer/filler interaction on the displacements of silica nanoparticles in gels by introducing them into poly(N,N dimethylacrylamide) gel (PDAM-NP gel) and polyacrylamide gel (PAM-NP gel). It is well known that PDAM chains are strongly adsorbed onto silica nanoparticles, while PAM chains are not. We carried out SAXS measurements on these gels under uniaxial elongation. Interestingly, we found that the SAXS scattering profiles of PDAM-NP and PAM-NP gels were totally different. A four-spot pattern was observed in the 2D structure factors of the PDAM-NP gel and was assigned to the movement of the nanoparticles in an affine way. On the other hand, as for the PAM-NP gel, a sharp peak was observed in the much lower q region than the prediction of affine deformation, indicating that the peak corresponds to the correlation peak of the high cross-linking region. These experimental findings may lead to the development of "probe-SAXS", which is a new technology for detecting nano-order inhomogeneity in hydrogels. PMID- 27181439 TI - Early apoptosis real-time detection by label-free SERS based on externalized phosphatidylserine. AB - Apoptosis is a tightly regulated cellular process that plays an essential role in the development, aging, cancer biology, immune response, and pathogenesis of various diseases. Herein, we report a new SERS sensing strategy for in vitro sensitive detection of early apoptotic cells. The principle of this method is to in situ synthesize silver nanoparticles (AgNPs) on the phosphatidylserine (PS) of the apoptotic cell membrane during the early apoptosis, which enables distinguishing normal and apoptotic cells. The total assay time of the presented method is only 10 min, thus being faster, cheaper and simpler than current techniques for the detection of apoptosis. The intrinsic mechanism was verified by different approaches based on externalized phosphatidylserine. In addition, the detection process is real-time and label-free; i.e., the intrinsic SERS spectra from the cellular membrane are directly employed for apoptosis real-time detection, which avoids using additional chemical or biological reagents as external signal indicators. Therefore, our SERS approach may serve as a potentially practical tool for sensitive and real-time detection of early cell apoptosis, complementing the state-of-the-art strategies, e.g. flow cytometry. While further investigation is required to better understand the intrinsic mechanism of the in situ coating method, the current results may provide another choice for real-time detection of early apoptosis. PMID- 27181441 TI - AAOM Clinical Practice Statement: Subject: Medical History. PMID- 27181442 TI - AAOM Clinical Practice Statement: Subject: Risk Assessment. PMID- 27181440 TI - The fourth modality: immunotherapy for head and neck cancer hits pay dirt. PMID- 27181443 TI - AAOM Clinical Practice Statement: Subject: Dental Care for the Patient with an Oral Herpetic Lesion. PMID- 27181444 TI - Oral erythema multiforme: trends and clinical findings of a large retrospective: European case series. PMID- 27181445 TI - In reply: Oral erythema multiforme: trends and clinical findings of a large retrospective: European case series. PMID- 27181446 TI - Simultaneous removal of third molars and completion of a sagittal split osteotomy: effects of age and presence of third molars-a commentary. PMID- 27181447 TI - Reply to: "Simultaneous removal of third molars and completion of a sagittal split osteotomy: effects of age and presence of third molars". PMID- 27181448 TI - Intraoral administration of botulinum toxin for trigeminal neuropathic pain. AB - This article presents 2 cases of different neuropathic trigeminal pain conditions treated with intraoral botulinum toxin injections. There is a growing body of evidence to support the use of this substance when administered subcutaneously in the treatment of neuropathic pain, such as in extraoral injections for trigeminal neuralgia. However, reports of intraoral submucosal administration are still lacking. In the 2 cases presented here, neuropathic pain was refractory to treatment with an important intraoral peripheral component, so onabotulinum toxin A was introduced as an adjuvant therapy. The technique, doses, and dilution are discussed. The patients reported significant reductions in pain frequency and intensity, with minimal side effects of temporary mucosal dryness and smile droopiness. The analgesic benefits of botulinum toxin may be utilized to address intraoral neuropathic pain. Further studies are needed to confirm safety and effectiveness in larger samples. PMID- 27181449 TI - Accuracy and reliability of oral maxillofacial radiologists when evaluating cone beam computed tomography imaging for adenoid hypertrophy screening: a comparison with nasopharyngoscopy. AB - OBJECTIVE: To determine how accurate and reliable oral maxillofacial radiologists (OMFRs) are in screening for adenoid hypertrophy when using cone-beam computed tomography (CBCT) imaging compared with nasopharyngoscopy (NP). STUDY DESIGN: CBCT scans of 10 patients with distinct levels of adenoid hypertrophy were randomly selected. Fourteen board-certified OMFRs classified the levels of hypertrophy. The intraclass correlation coefficient (ICC) was used to assess accuracy by comparing their diagnosis against an NP diagnosis, which is the reference standard. OMFRs' interreliability was assessed. Kappa statistics were used to analyze dichotomous data from healthy and unhealthy patients. RESULTS: Overall, the reliability among OMFRs was good (ICC = 0.79 with confidence interval [CI] 0.63-0.93). The "statistical mode" was very good (ICC = 0.81; CI 0.43-0.94). The accuracy of OMFRs against NP was good (ICCmean = 0.69; CI 0.43 0.94). On average, the Kappa statistics (Kmean = 0.77; CI 0.62-0.92) demonstrated a good agreement between OMFRs and NP diagnoses. The individualized results from each evaluator were presented and investigated according to their performance. CONCLUSIONS: Compared with the reference standard, the accuracy of OMFRs to classify adenoid hypertrophy on a four-level scale was moderate to strong and improved when adenoid hypertrophy was classified as healthy or unhealthy. The reliability of the OMFRs was greater than 80%, assuring their consistency and reliability on screening adenoids hypertrophy via CBCT. PMID- 27181450 TI - Can tongue shadow in panoramic radiographs be avoided by using the tongue repositioning maneuver? AB - OBJECTIVE: The purpose of this study was to evaluate the use of the tongue repositioning maneuver (TRM) during panoramic radiography so as to avoid the error of tongue shadow. STUDY DESIGN: A total of 300 panoramic radiographs were evaluated. One hundred and fifty orthopantomograms with conventional positioning technique were used as a control group, while other 150 were taken with the patient performing the TRM. The tongue shadow was measured in each radiograph in the first molar regions bilaterally and in the midsagittal plane. Wilcoxon Mann Whitney U-Test was used to test the significance difference between the groups. RESULTS: The tongue-palate distance in the study group was reduced from a mean value of 6.4 mm to 1 mm in the right first molar, 8.0 mm to 2.2 mm in the midsagittal region, and 6.6 mm to 1.2 mm in the left first molar position. Statistical evaluation exhibited significant differences of tongue shadow at all measuring sites between study and control group (P < .0001). CONCLUSIONS: The present study demonstrates that the TRM leads to a substantial reduction of the tongue position error in panoramic radiography. PMID- 27181451 TI - Derivation of an occupational exposure limit for an inhalation analgesic methoxyflurane (Penthrox((r))). AB - Methoxyflurane (MOF) a haloether, is an inhalation analgesic agent for emergency relief of pain by self administration in conscious patients with trauma and associated pain. It is administered under supervision of personnel trained in its use. As a consequence of supervised use, intermittent occupational exposure can occur. An occupational exposure limit has not been established for methoxyflurane. Human clinical and toxicity data have been reviewed and used to derive an occupational exposure limit (referred to as a maximum exposure level, MEL) according to modern principles. The data set for methoxyflurane is complex given its historical use as anaesthetic. Distinguishing clinical investigations of adverse health effects following high and prolonged exposure during anaesthesia to assess relatively low and intermittent exposure during occupational exposure requires an evidence based approach to the toxicity assessment and determination of a critical effect and point of departure. The principal target organs are the kidney and the central nervous system and there have been rare reports of hepatotoxicity, too. Methoxyflurane is not genotoxic based on in vitro bacterial mutation and in vivo micronucleus tests and it is not classifiable (IARC) as a carcinogenic hazard to humans. The critical effect chosen for development of a MEL is kidney toxicity. The point of departure (POD) was derived from the concentration response relationship for kidney toxicity using the benchmark dose method. A MEL of 15 ppm (expressed as an 8 h time weighted average (TWA)) was derived. The derived MEL is at least 50 times higher than the mean observed TWA (0.23 ppm) for ambulance workers and medical staff involved in supervising use of Penthrox. In typical treatment environments (ambulances and treatment rooms) that meet ventilation requirements the derived MEL is at least 10 times higher than the modelled TWA (1.5 ppm or less) and the estimated short term peak concentrations are within the MEL. The odour threshold for MOF of 0.13-0.19 ppm indicates that the odour is detectable well below the MEL. Given the above considerations the proposed MEL is health protective. PMID- 27181452 TI - Chemical, physical, and in vitro characterization of research cigarettes containing denicotinized tobacco. AB - The use of very low nicotine tobacco cigarettes is currently being investigated as a possible harm reduction strategy. Here, we report the smoke chemistry, toxicity, and physical characteristics of very low nicotine cigarettes that were made using blended tobacco processed through a supercritical CO2 fluid extraction, which resulted in elimination of 96% of nicotine content (denicotinized (denic) tobacco). Three types of test cigarettes (TCs) were manufactured with tobacco filler containing 100% denic tobacco (TC100), 50% denic tobacco and 50% unextracted tobacco (TC50/50), and 100% unextracted tobacco (TC0). Mainstream smoke (MS) was generated for measurement of 46 analytes and cytotoxicity and mutagenicity determination. Analysis of physical characteristics of TCs demonstrated they were well made with <5% variability among cigarettes for most parameters measured. We observed significant changes in the levels of smoke constituents, including decreases in formaldehyde, nitrosamines, and phenol, and increases in aliphatic hydrocarbons, aliphatic nitrogen compounds, aromatic amines, halogen compounds, and metals. Use of denic tobacco resulted in changes in the chemical composition of MS, but these changes did not modify biological activity as measured in the mutagenicity and cytotoxicity assays. PMID- 27181454 TI - Predicting anxiety responses to halogenated glucocorticoid drugs using the hexobarbital sleep time test. AB - Glucocorticoids (GCs) are used to treat numerous diseases, but their use in limited by adverse side effects. One such effect is occasional increased anxiety. Since the intensity of hepatic microsomal oxidation has been shown to alter responses to GC, we examined the possibility that rats with lower rates of hepatic GC metabolism would have increased anxiety. We hypothesized that the resulting, excessive GC would stimulate brain monoamine oxidase A (MAO-A), which would reduce brain serotonin, and thereby increase anxiety. Hepatic microsomal oxidative intensity was evaluated by the hexobarbital sleep time (HST) test. Results showed that rats with lower rates of hepatic GC metabolism had elevated brain MAO-A activity, reduced brain serotonin, and more anxiety than rats with higher rates of hepatic GC metabolism. We suggest that the HST test, as an integrative test of microsomal oxidation status, should be useful for predicting individual sensitivity to GC and to other drugs metabolized by the hepatic microsomal oxidation system. PMID- 27181453 TI - Chemical-specific adjustment factors (inter-species toxicokinetics) to establish the ADI for steviol glycosides. AB - The acceptable daily intake (ADI) of commercially available steviol glycosides is currently 0-4 mg/kg body weight (bw)/day, based on application of a 100-fold uncertainty factor to a no-observed-adverse-effect-level value from a chronic rat study. Within the 100-fold uncertainty factor is a 10-fold uncertainty factor to account for inter-species differences in toxicokinetics (4-fold) and toxicodynamics (2.5-fold). Single dose pharmacokinetics of stevioside were studied in rats (40 and 1000 mg/kg bw) and in male human subjects (40 mg/kg bw) to generate a chemical-specific, inter-species toxicokinetic adjustment factor. Tmax values for steviol were at ~8 and ~20 h after administration in rats and humans, respectively. Peak concentrations of steviol were similar in rats and humans, while steviol glucuronide concentrations were significantly higher in humans. Glucuronidation in rats was not saturated over the dose range 40-1000 mg/kg bw. The AUC0-last for steviol was approximately 2.8-fold greater in humans compared to rats. Chemical-specific adjustment factors for extrapolating toxicokinetics from rat to human of 1 and 2.8 were established based on Cmax and AUC0-last data respectively. Because these factors are lower than the default value of 4.0, a higher ADI for steviol glycosides of between 6 and 16 mg/kg bw/d is justified. PMID- 27181455 TI - Hybrid silicon honeycomb/organic solar cells with enhanced efficiency using surface etching. AB - Silicon (Si) nanostructure-based photovoltaic devices are attractive for their excellent optical and electrical performance, but show lower efficiency than their planar counterparts due to the increased surface recombination associated with the high surface area and roughness. Here, we demonstrate an efficiency enhancement for hybrid nanostructured Si/polymer solar cells based on a novel Si honeycomb (SiHC) structure using a simple etching method. SiHC structures are fabricated using a combination of nanosphere lithography and plasma treatment followed by a wet chemical post-etching. SiHC has shown superior light-trapping ability in comparison with the other Si nanostructures, along with a robust structure. Anisotropic tetramethylammonium hydroxide etching not only tunes the final surface morphologies of the nanostructures, but also reduces the surface roughness leading to a lower recombination rate in the hybrid solar cells. The suppressed recombination loss, benefiting from the reduced surface-to-volume ratio and roughness, has resulted in a high open-circuit voltage of 600 mV, a short-circuit current of 31.46 mA cm(-2) due to the light-trapping ability of the SiHCs, and yields a power conversion efficiency of 12.79% without any other device structure optimization. PMID- 27181457 TI - Biological strategy for the fabrication of highly ordered aragonite helices: the microstructure of the cavolinioidean gastropods. AB - The Cavolinioidea are planktonic gastropods which construct their shells with the so-called aragonitic helical fibrous microstructure, consisting of a highly ordered arrangement of helically coiled interlocking continuous crystalline aragonite fibres. Our study reveals that, despite the high and continuous degree of interlocking between fibres, every fibre has a differentiated organic-rich thin external band, which is never invaded by neighbouring fibres. In this way, fibres avoid extinction. These intra-fibre organic-rich bands appear on the growth surface of the shell as minuscule elevations, which have to be secreted differentially by the outer mantle cells. We propose that, as the shell thickens during mineralization, fibre secretion proceeds by a mechanism of contact recognition and displacement of the tips along circular trajectories by the cells of the outer mantle surface. Given the sizes of the tips, this mechanism has to operate at the subcellular level. Accordingly, the fabrication of the helical microstructure is under strict biological control. This mechanism of fibre-by fibre fabrication by the mantle cells is unlike that any other shell microstructure. PMID- 27181456 TI - Initiation Strategies for Renal-Replacement Therapy in the Intensive Care Unit. AB - BACKGROUND: The timing of renal-replacement therapy in critically ill patients who have acute kidney injury but no potentially life-threatening complication directly related to renal failure is a subject of debate. METHODS: In this multicenter randomized trial, we assigned patients with severe acute kidney injury (Kidney Disease: Improving Global Outcomes [KDIGO] classification, stage 3 [stages range from 1 to 3, with higher stages indicating more severe kidney injury]) who required mechanical ventilation, catecholamine infusion, or both and did not have a potentially life-threatening complication directly related to renal failure to either an early or a delayed strategy of renal-replacement therapy. With the early strategy, renal-replacement therapy was started immediately after randomization. With the delayed strategy, renal-replacement therapy was initiated if at least one of the following criteria was met: severe hyperkalemia, metabolic acidosis, pulmonary edema, blood urea nitrogen level higher than 112 mg per deciliter, or oliguria for more than 72 hours after randomization. The primary outcome was overall survival at day 60. RESULTS: A total of 620 patients underwent randomization. The Kaplan-Meier estimates of mortality at day 60 did not differ significantly between the early and delayed strategies; 150 deaths occurred among 311 patients in the early-strategy group (48.5%; 95% confidence interval [CI], 42.6 to 53.8), and 153 deaths occurred among 308 patients in the delayed-strategy group (49.7%, 95% CI, 43.8 to 55.0; P=0.79). A total of 151 patients (49%) in the delayed-strategy group did not receive renal-replacement therapy. The rate of catheter-related bloodstream infections was higher in the early-strategy group than in the delayed-strategy group (10% vs. 5%, P=0.03). Diuresis, a marker of improved kidney function, occurred earlier in the delayed-strategy group (P<0.001). CONCLUSIONS: In a trial involving critically ill patients with severe acute kidney injury, we found no significant difference with regard to mortality between an early and a delayed strategy for the initiation of renal-replacement therapy. A delayed strategy averted the need for renal-replacement therapy in an appreciable number of patients. (Funded by the French Ministry of Health; ClinicalTrials.gov number, NCT01932190.). PMID- 27181458 TI - Relationship between Fusarium spp. diversity and mycotoxin contents of mature grains in southern Belgium. AB - Over a 4-year period (2010-13), a survey aiming at determining the occurrence of Fusarium spp. and their relations to mycotoxins in mature grains took place in southern Belgium. The most prevalent species were F. graminearum, F. avenaceum, F. poae and F. culmorum, with large variations between years and locations. An even proportion of mating type found for F. avenaceum, F. culmorum, F. cerealis and F. tricinctum is usually a sign of ongoing sexual recombination. In contrast, an unbalanced proportion of mating type was found for F. poae and no MAT1-2 allele was present in the F. langsethiae population. Genetic chemotyping indicates a majority of deoxynivalenol (DON)-producing strains in F. culmorum (78%, all 3-ADON producers) and F. graminearum (95%, mostly 15-ADON producers), while all F. cerealis strains belong to the nivalenol (NIV) chemotype. Between 2011 and 2013, DON, NIV, enniatins (ENNs) and moniliformin (MON) were found in each field in various concentrations. By comparison, beauvericin (BEA) was scarcely detected and T-2 toxin, zearalenone and alpha- and beta-zearalenols were never detected. Principal component analysis revealed correlations of DON with F. graminearum, ENNs and MON with F. avenaceum and NIV with F. culmorum, F. cerealis and F. poae. BEA was associated with the presence of F. tricinctum and, to a lesser extent, with the presence of F. poae. The use of genetic chemotype data revealed that DON concentrations were mostly influenced by DON-producing strains of F. graminearum and F. culmorum, whereas the concentrations of NIV were influenced by the number of NIV-producing strains of both species added to the number of F. cerealis and F. poae strains. This study emphasises the need to pay attention to less-studied Fusarium spp. for future Fusarium head blight management strategies, as they commonly co-occur in the field and are associated with a broad spectrum of mycotoxins. PMID- 27181459 TI - Site-directed spin labeling of proteins for distance measurements in vitro and in cells. AB - Site-directed spin labeling (SDSL) in combination with electron paramagnetic resonance (EPR) spectroscopy allows studying the structure, dynamics, and interactions of proteins via distance measurements in the nanometer range. We here give an overview of available spin labels, the strategies for their introduction into proteins, and the associated potentials for protein structural studies in vitro and in the context of living cells. PMID- 27181461 TI - Elucidation of the surface structure-selectivity relationship in ethanol electro oxidation over platinum by density functional theory. AB - We have successfully built a general framework to comprehend the structure selectivity relationship in ethanol electrooxidation on platinum by density functional theory calculations. Based on the reaction mechanisms on three basal planes and five stepped surfaces, it was found that only (110) and n(111) * (110) sites can enhance CO2 selectivity but other non-selective step sites are more beneficial to activity. PMID- 27181460 TI - Photodynamic action of palmatine hydrochloride on colon adenocarcinoma HT-29 cells. AB - Palmatine hydrochloride (PaH) is a natural active compound from a traditional Chinese medicine (TCM). The present study aims to evaluate the effect of PaH as a new photosensitizer on colon adenocarcinoma HT-29 cells upon light irradiation. Firstly, the absorption and fluorescence spectra of PaH were measured using a UV vis spectrophotometer and RF-1500PC spectrophotometer, respectively. Singlet oxygen ((1)O2) production of PaH was determined using 1, 3-diphenylisobenzofuran (DPBF). Dark toxicity of PaH was estimated using the 3-(4, 5-dimethylthiazol-2 yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Cellular uptake of PaH in HT-29 cells was detected at different time intervals. Subellular localization of PaH in HT-29 cells was observed using confocal laser fluorescence microscopy. For photodynamic treatment, HT-29 cells were incubated with PaH and then irradiated by visible light (470nm) from a LED light source. Photocytotoxicity was investigated 24h after photodynamic treatment using MTT assay. Cell apoptosis was observed 18h after photodynamic treatment using a flow cytometry with Annexin V/PI staining. Results showed that PaH has an absorption peak in the visible region from 400nm to 500nm and a fluorescence emission peak at 406nm with an excitation wavelength of 365nm. PaH was activated by the 470nm visible light from a LED light source to produce (1)O2. Dark toxicity showed that PaH alone treatment had no cytotoxicity to HT-29 cancer cells and NIH-3T3 normal cells after incubation for 24h. After incubation for 40min, the cellular uptake of PaH reached to the maximum and PaH was located in mitochondria. Photodynamic treatment of PaH demonstrated a significant photocytotoxicity on HT-29 cells. The rate of cell death increased significantly in a PaH concentration-dependent and light dose-dependent manner. Further evaluation revealed that the early and late apoptotic rate of HT-29 cells increased remarkably up to 21.54% and 5.39% after photodynamic treatment of PaH at the concentration of 5MUM and energy density of 10.8J/cm(2). Our findings demonstrated that PaH as a naturally occurring photosensitizer has potential in photodynamic therapy on colon adenocarcinoma. PMID- 27181462 TI - Nanostructured lipid carriers, solid lipid nanoparticles, and polymeric nanoparticles: which kind of drug delivery system is better for glioblastoma chemotherapy? AB - CONTEXT: Glioblastoma is a malignant brain tumor originating in the central nervous system. Successfully therapy of this disease required the efficient delivery of therapeutic agents to the tumor cells and tissues. Delivery of anticancer drugs using novel nanocarriers is promising in glioma treatment. OBJECTIVE: Polymeric nanoparticles (PNPs), solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs) were constructed for the delivery of temozolomide (TMZ). The anti-tumor effects of the three kinds of nanocarriers were compared to provide the optimum choice for gliomatosis cerebri treatment. METHODS: TMZ-loaded PNPs (T-PNPs), SLNs (T-SLNs), and NLCs (T-NLCs) were formulated. Their particle size, zeta potential, drug encapsulation efficiency (EE), and drug loading (DL) capacity were evaluated. Anti-tumor efficacies of the three kinds of nanocarriers were evaluated on U87 malignant glioma cells (U87 MG cells) and mice-bearing malignant glioma model. RESULTS: T-NLCs displayed the best anti-tumor activity than other formulations in vivo and in vitro. The most significantly glioma inhibition was observed on NLCs formulations than PNPs and SLNs. CONCLUSION: This work demonstrates that NLCs can deliver TMZ into U87MG cells more efficiently, with higher inhibition efficacy than PNPs and SLNs. T NLCs could be an excellent drug delivery system for glioblastoma chemotherapy. PMID- 27181483 TI - Fast electronic resistance switching involving hidden charge density wave states. AB - The functionality of computer memory elements is currently based on multi stability, driven either by locally manipulating the density of electrons in transistors or by switching magnetic or ferroelectric order. Another possibility is switching between metallic and insulating phases by the motion of ions, but their speed is limited by slow nucleation and inhomogeneous percolative growth. Here we demonstrate fast resistance switching in a charge density wave system caused by pulsed current injection. As a charge pulse travels through the material, it converts a commensurately ordered polaronic Mott insulating state in 1T-TaS2 to a metastable electronic state with textured domain walls, accompanied with a conversion of polarons to band states, and concurrent rapid switching from an insulator to a metal. The large resistance change, high switching speed (30 ps) and ultralow energy per bit opens the way to new concepts in non-volatile memory devices manipulating all-electronic states. PMID- 27181484 TI - Critical phenomena of emergent magnetic monopoles in a chiral magnet. AB - Second-order continuous phase transitions are characterized by symmetry breaking with order parameters. Topological orders of electrons, characterized by the topological index defined in momentum space, provide a distinct perspective for phase transitions, which are categorized as quantum phase transitions not being accompanied by symmetry breaking. However, there are still limited observations of counterparts in real space. Here we show a real-space topological phase transition in a chiral magnet MnGe, hosting a periodic array of hedgehog and antihedgehog topological spin singularities. This transition is driven by the pair annihilation of the hedgehogs and antihedgehogs acting as monopoles and antimonopoles of the emergent electromagnetic field. Observed anomalies in the magnetoresistivity and phonon softening are consistent with the theoretical prediction of critical phenomena associated with enhanced fluctuations of emergent field near the transition. This finding reveals a vital role of topology of the spins in strongly correlated systems. PMID- 27181485 TI - Evaluation of simulation learning materials use to fill the gap in Japanese dental English education. AB - Even though English is most frequently the common language when the patient's native language differs from that of a dentist, the opportunities for Japanese undergraduate dental students to learn dental English are now quite limited. The purposes of our study were to investigate: the effectiveness and feasibility of the computer-assisted simulation materials as one solution strategy for dental English education in Japan, and the needs and demands for dental English from the learners' side. Interactive simulation materials for medical interviews in English and clinical cases which were translated to English, were delivered via Learning Management System (LMS) to nineteen trainee residents of dentistry (residents). Evaluation for the materials, learners' knowledge and interests in the contents, and ease of operation were obtained by post-questionnaire (response rates were 100% and 95%, respectively). Both questionnaire-surveys received positive feedback toward the materials, yet 47% answered that they lacked the level of knowledge about contents of the medical interview in English. Results were sufficient to suggest that the residents would like to have the opportunity to study or practice medical interview in English, or English related to dentistry, and that the simulation materials could be one of the solution strategies for opportunity provision. PMID- 27181486 TI - Relationship between regional population and healthcare delivery in Japan. AB - In order to address regional inequality in healthcare delivery in Japan, healthcare districts were established in 1985. However, regional healthcare delivery has now become a national issue because of population migration and the aging population. In this study, the state of healthcare delivery at the district level is examined by analyzing population, the number of physicians, and the number of hospital beds. The results indicate a continuing disparity in healthcare delivery among districts. We find that the rate of change in population has a strong positive correlation with that in the number of physicians and a weak positive correlation with that in the number of hospital beds. In addition, principal component analysis is performed on three variables: the rate of change in population, the number of physicians per capita, and the number of hospital beds per capita. This analysis suggests that the two principal components contribute 90.1% of the information. The first principal component is thought to show the effect of the regulations on hospital beds. The second principal component is thought to show the capacity to recruit physicians. This study indicates that an adjustment to the regulations on hospital beds as well as physician allocation by public funds may be key to resolving the impending issue of regionally disproportionate healthcare delivery. PMID- 27181487 TI - Systematic cytological evaluation and immunocytochemistry of minichromosome maintenance protein 2 and p53 significantly improve cytological diagnosis of pancreaticobiliary adenocarcinoma. AB - Endoscopic retrograde cholangiopancreatography (ERCP) brushing cytology often cannot distinguish adenocarcinoma from reactive epithelial changes. We attempted to improve the diagnostic sensitivity of ERCP using the following methods: systematic cytological evaluation, immunocytochemical examination of minichromosome maintenance proteins (MCM) 2 and p53, and a combination of these methods. ERCP specimens from 53 patients (13 benign and 40 malignant cases) were studied. First, we reclassified the cases into three categories according to the systematic cytological evaluation: negative, suspicious, and positive. Secondly, immunocytochemistry was performed for MCM 2 and p53. The cut-off values were set at 25% labeling index (LI) for MCM 2 and 10% LI for p53, respectively. We evaluated the sensitivity, specificity, and diagnostic accuracy. The sensitivity of the systematic cytological evaluation alone did not improve significantly, compared with the original screening examination (77% vs. 68%). The sensitivity of immunocytochemistry for MCM 2 and p53 was 90% (P < 0.05) and 68%, respectively. Applying only the suspicious or positive categories, the sensitivity improved significantly to 93% for the combination of systematic cytological evaluation and immunocytochemistry for MCM 2 and p53 (P < 0.01). In conclusion, the combination of morphology and immunocytochemistry for MCM 2 and p53 may help to overcome the diagnostic cytological difficulties of pancreaticobiliary adenocarcinoma. PMID- 27181488 TI - Usefulness of the transfer function index for diagnosing peripheral arterial disease in patients with arterial calcification. AB - The aim of this study was to investigate which parameters among the ankle brachial index (ABI), toe brachial pressure index (TBI) and transfer function index (TFI) are useful to accurately diagnose PAD in patients with / without arterial calcification, who have undergone some type of diagnostic imaging. PATIENTS AND METHODS: A total of 102 patients with 192 limbs (mean age: 72.0 +/- 8.4 years) underwent plain radiography, ABI, TBI and TFI. A receiver operating characteristics (ROC) analysis was performed to assess possible threshold values that predict PAD in these patients. RESULTS: T he a rea u nder t he c urve ( AUC) o f t he ABI, TBI and TFI were 83.0%, 87.9%, 93.1% in the all limbs group, respectively. In the non-calcified lesion group, the AUC of the ABI, TBI and TFI were 94.4%, 87.9%, 93.1%, respectively. In the calcified lesion group, the AUC of the ABI, TBI and TFI were 71.4%, 87.9% and 92.9%, respectively. CONCLUSIONS: A cut-off value of TFI ? 1.025 exhibits a higher AUC for detecting the presence of PAD than the ABI and TBI. Therefore, the TFI is considered to be useful to estimate the presence of PAD in all types of patients, especially those with arterial calcification. PMID- 27181489 TI - Plain Radiographs are a Useful Substitute for Computed Tomography in Evaluating Acetabular Cup Version. AB - BACKGROUND: The purpose of this study is to compare acetabular component version measurements from cross-table lateral (XTL) radiographs, anteroposterior pelvis (AP-P) and anteroposterior hip (AP-H) radiographs, and axial pelvic computed tomography (CT) scans. METHODS: One hundred fifty hips met our inclusion criteria of having a CT, XTL, and AP-P done postoperatively. Version was measured by 2 authors. Pearson regression analysis assessed correlation between versions of the modalities. Analysis of variance testing compared the averages of the values as a whole and based on demographics. When available, comparisons were also done with AP-H radiographs. RESULTS: Mean version for XTL and CT scan was 21.7 degrees and 23.8 degrees , respectively, whereas that from AP-P and AP-H radiographs was 12.5 degrees and 17.2 degrees , respectively. XTL and AP-H version measures were closely correlated with CT (P = .81), whereas AP-P measurements were only moderately correlated with CT (P = .75). AP-P and AP-H were significantly (P < .05) different from CT, whereas XTL was not (P = .36). CONCLUSION: The XTL radiograph remains a useful, cheaper, and safer substitute for CT scan when assessing supine version in the postoperative setting. PMID- 27181490 TI - Can a Silver-Coated Arthrodesis Implant Provide a Viable Alternative to Above Knee Amputation in the Unsalvageable, Infected Total Knee Arthroplasty? AB - BACKGROUND: In the unsalvageable, infected total knee arthroplasty, knee arthrodesis is one treatment option with lower reported reinfection rates compared with repeated 2-stage revision and improved function compared with amputation. One possible method for reducing incidence of recurrent infection treated by arthrodesis is the use of a silver-coated implant. We report our experience of silver-coated arthrodesis nails used for managing infected revision arthroplasty. We primarily assess the rate of reinfection and rate of amputation and report functional outcome measures. METHODS: Retrospective analysis of all patients undergoing knee arthrodesis with a silver-coated arthrodesis nail between 2008 and 2014. Patient-reported data were recorded prearthrodesis and postarthrodesis (Oxford Knee Score and Short Form-36) as well as evidence of recurrent of infection, subsequent surgery, and the necessity for amputation. RESULTS: Eight patients underwent arthrodesis using the silver-coated arthrodesis nail. Mean duration of follow-up was 16 months (5-35 months). At the point of follow-up, there were no amputations, deaths, or implant revisions. One case of recurrent infection was successfully treated with washout and debridement. The mean prearthrodesis and postarthrodesis Oxford Knee Score difference was +8.9 points (P = .086) with significantly improved pain (P = .019), night pain (P = .021), and ease of standing (P = .003). CONCLUSION: Arthrodesis of the knee using a silver-coated intramedullary device is successful in eradicating infection and allowing limb conservation. Where infection does recur, this can be successfully treated with implant retention. The use of a silver-coated arthrodesis nail should be considered as an alternative to amputation for patients with a multiply revised and infected total knee arthroplasty. PMID- 27181491 TI - The Rising Incidence of Degenerative and Posttraumatic Osteoarthritis of the Knee in the United States Military. AB - BACKGROUND: This investigation sought to quantify incidence rates (IRs) and risk factors for primary and secondary (ie, posttraumatic) osteoarthritis (OA) of the knee in an active military population. METHODS: We performed a retrospective review of United States military active duty servicemembers with first-time diagnosis of primary (International Classification of Disease, 9th Edition code: 715.16) and secondary (International Classification of Disease, 9th Edition code: 715.26) OA of the knee between 2005 and 2014 using the Defense Medical Epidemiology Database. IRs and 95% CIs were expressed per 1000 person-years, with stratified subgroup analysis adjusted for sex, age, race, military rank, and branch of military service. Relative risk factors were evaluated using IR ratios and multiple regression analysis. RESULTS: A total of 21,318 cases of OA of the knee were identified among an at-risk population of 13,820,906 person-years for an overall IR of 1.54 per 1000 person-years, including 19,504 cases of primary (IR: 1.41) and 1814 cases of secondary OA (IR: 0.13). The IRs of both primary and secondary OA increased significantly from 2005 to 2014. Increasing age (P < .0001); black race (P < .001); senior military rank (P < .0001); and Army, Marines, and Air Force services (P < .0001) were significantly associated with an increased risk for knee OA. CONCLUSION: This study is the first large-scale report of knee OA in a young athletic population. An increasing incidence and several risk factors for knee OA were identified, indicating a need for better preventative strategies and forecasting the increased anticipated demands for knee arthroplasty among US military servicemembers. PMID- 27181492 TI - The Outcome of 69 Recemented Hip Femoral Prostheses Performed by One Surgeon 22 40 Years Ago. AB - BACKGROUND: There is a lack of long-term data on cement-in-cement technique in revision of failed hip femoral stem. METHODS: We present the outcome of 69 consecutive recemented femoral prostheses, performed by one surgeon (GH) 22-40 years ago. Four patients (4 hips) were lost to follow-up. Sixty-three patients (65 hips) were followed for their lifetime or until the time of the preparation of the study. The study population consisted of 18 failed hemiarthroplasties and 47 failed total hip arthroplasties. RESULTS: The 23-year probability of survival for the recemented femoral components, with re-revision for any reason and resection arthroplasty as the end point, was 73.6% (61.8%-85.4%) and, with re revision for aseptic loosening as the end point, was 82.2% (71.4%-93%). CONCLUSION: Our follow-up study at 22-40 years, after recemented hip femoral prostheses, shows that recementing works well in selected cases. PMID- 27181493 TI - Letter to the Editor on "Total Joint Arthroplasty: Trends in Medicare Reimbursement and Implant Prices". PMID- 27181494 TI - Crouzonodermoskeletal Syndrome with Hypoplasia of Corpus Callosum and Inferior Vermis. PMID- 27181495 TI - Universal classification of twisted, strained and sheared graphene moire superlattices. AB - Moire superlattices in graphene supported on various substrates have opened a new avenue to engineer graphene's electronic properties. Yet, the exact crystallographic structure on which their band structure depends remains highly debated. In this scanning tunneling microscopy and density functional theory study, we have analysed graphene samples grown on multilayer graphene prepared onto SiC and on the close-packed surfaces of Re and Ir with ultra-high precision. We resolve small-angle twists and shears in graphene, and identify large unit cells comprising more than 1,000 carbon atoms and exhibiting non-trivial nanopatterns for moire superlattices, which are commensurate to the graphene lattice. Finally, a general formalism applicable to any hexagonal moire is presented to classify all reported structures. PMID- 27181496 TI - Photonic reagents for concentration measurement of flu-orescent proteins with overlapping spectra. AB - By exploiting photonic reagents (i.e., coherent control by shaped laser pulses), we employ Optimal Dynamic Discrimination (ODD) as a novel means for quantitatively characterizing mixtures of fluorescent proteins with a large spectral overlap. To illustrate ODD, we simultaneously measured concentrations of in vitro mixtures of Enhanced Blue Fluorescent Protein (EBFP) and Enhanced Cyan Fluorescent Protein (ECFP). Building on this foundational study, the ultimate goal is to exploit the capabilities of ODD for parallel monitoring of genetic and protein circuits by suppressing the spectral cross-talk among multiple fluorescent reporters. PMID- 27181497 TI - Observation of phase-retention behavior of the HC(NH2)2PbI3 black perovskite polymorph upon mesoporous TiO2 scaffolds. AB - The alpha->delta phase transition, which occurs favorably in planar films of a black alpha-HC(NH2)2PbI3 (alpha-FAPbI3) perovskite in the amibent, is retarded when alpha-FAPbI3 is deposited upon mesoporous TiO2 scaffolds. It is hypothesized that this is due to the synergistic effect of the partial encapsulation of alpha FAPbI3 by the mesoporous TiO2 and the elevated activation energy for the transition reaction associated with the substantial increase of the TiO2/alpha FAPbI3 interfacial area in the mesoscopic system. PMID- 27181498 TI - Managing non-alcoholic fatty liver disease in diabetes: Challenges and opportunities. PMID- 27181499 TI - A Non-Anticoagulant Fraction of Heparin Inhibits Leukocyte Diapedesis into the Lung by an Effect on Platelets. AB - We have investigated whether the mechanism by which the non-anticoagulant N acetyl-de-O-sulfated-heparin (NSH) inhibits leukocyte infiltration is mediated by an effect on platelet function. We show that oral treatment with two doses of NSH significantly inhibits eosinophil and neutrophil recruitment into the lungs. Intravital microscopy analysis shows that NSH inhibits leukocyte and platelet diapedesis in the microcirculation of the cremaster muscle and in the trachea. More importantly, there were significantly lower numbers of leukocytes recruited into the lung in response to LPS in thrombocytopenic mice when transfused with platelets pretreated with NSH in vitro when compared with mice transfused with untreated platelets. Using intravital analysis of the microvasculature of the cremaster muscle, we have demonstrated that the reinfusion of activated platelets significantly re-established leukocyte diapedesis in response to LPS but that this effect was not observed when platelets were pretreated in vitro with NSH. Finally, we investigated whether the effect of NSH altered the expression of adhesion molecules on the surface of platelets and leukocytes in blood samples collected from mice treated orally with NSH. Our results demonstrate that NSH significantly inhibited the detection of P-selectin as evaluated by flow cytometry, confirming that part of the antiinflammatory action of NSH is via an effect on platelet function. PMID- 27181500 TI - Development and validation of HPLC method for vicenin-1 isolated from fenugreek seeds in rat plasma: application to pharmacokinetic, tissue distribution and excretion studies. AB - CONTEXT: Vicenin-1, a flavonol glycoside, has potent platelet aggregation inhibition, antioxidant, radioprotectants and anti-inflammatory activities. OBJECTIVE: To establish a rapid, simple, precise and sensitive high-performance liquid chromatography (HPLC) method for determination of vicenin-1 in rat plasma, and to investigate the pharmacokinetics, tissue distribution and excretion after a single 60 mg/kg oral dose in rats. MATERIALS AND METHODS: Vicenin-1 was extracted by solid-liquid extraction through Tulsicon(r) ADS-400 (0.40-1.2 mm). Chromatographic separation was achieved by HPLC with a C18 column with a mobile phase composed of water and acetonitrile (75:25 v/v) and a flow rate of 1 mL/min along with UV detection at 210 nm. RESULTS: Good linearity of calibration curve was found between 10.5 and 100.5 MUg/mL (R2 = 0.995) for plasma and tissue, whereas 2.5-500 MUg/mL (R2 = 0.999) for the urine and stool samples. The extraction recoveries were 98.51-99.58% for vicenin-1 in plasma, whereas intra day and inter-day precision were validated by relative standard deviation (%RSD), that came in the ranges of 1.16-1.79% and 1.28-1.73%, respectively. The pharmacokinetics results showed Cmax (7.039 MUg/mL) and Tmax (2 h) after oral administration of vicenin-1. Tissue distribution study showed that the highest concentration of vicenin-1 was achieved in the liver followed by the lung. Approximately 24.2% of its administered dose was excreted via urinary excretion route. CONCLUSION: The first-pass metabolism, poor solubility and presence of reducing sugar moiety in vicenin-1 may decrease its bioavailability. The developed method is sensitive, specific and was successfully applied to the pharmacokinetics, tissue distribution and excretion studies of vicenin-1 in rats. PMID- 27181501 TI - Three-step channel conformational changes common to DNA packaging motors of bacterial viruses T3, T4, SPP1, and Phi29. AB - The DNA packaging motor of dsDNA bacterial viruses contains a head-tail connector with a channel for the genome to enter during assembly and to exit during host infection. The DNA packaging motor of bacterial virus phi29 was recently reported to use the "One-way revolving" mechanism for DNA packaging. This raises a question of how dsDNA is ejected during infection if the channel acts as a one way inward valve. Here we report a three step conformational change of the portal channel that is common among DNA translocation motors of bacterial viruses T3, T4, SPP1, and phi29. The channels of these motors exercise three discrete steps of gating, as revealed by electrophysiological assays. The data suggest that the three step channel conformational changes occur during DNA entry process, resulting in a structural transition in preparation for DNA movement in the reverse direction during ejection. PMID- 27181502 TI - Probabilities of Dilating Vesicoureteral Reflux in Children with First Time Simple Febrile Urinary Tract Infection, and Normal Renal and Bladder Ultrasound. AB - PURPOSE: We evaluated risk factors and assessed predicted probabilities for grade III or higher vesicoureteral reflux (dilating reflux) in children with a first simple febrile urinary tract infection and normal renal and bladder ultrasound. MATERIALS AND METHODS: Data for 167 children 2 to 72 months old with a first febrile urinary tract infection and normal ultrasound were compared between those who had dilating vesicoureteral reflux (12 patients, 7.2%) and those who did not. Exclusion criteria consisted of history of prenatal hydronephrosis or familial reflux and complicated urinary tract infection. The logistic regression model was used to identify independent variables associated with dilating reflux. Predicted probabilities for dilating reflux were assessed. RESULTS: Patient age and prevalence of nonEscherichia coli bacteria were greater in children who had dilating reflux compared to those who did not (p = 0.02 and p = 0.004, respectively). Gender distribution was similar between the 2 groups (p = 0.08). In multivariate analysis older age and nonE. coli bacteria independently predicted dilating reflux, with odds ratios of 1.04 (95% CI 1.01-1.07, p = 0.02) and 3.76 (95% CI 1.05-13.39, p = 0.04), respectively. The impact of nonE. coli bacteria on predicted probabilities of dilating reflux increased with patient age. CONCLUSIONS: We support the concept of selective voiding cystourethrogram in children with a first simple febrile urinary tract infection and normal ultrasound. Voiding cystourethrogram should be considered in children with late onset urinary tract infection due to nonE. coli bacteria since they are at risk for dilating reflux even if the ultrasound is normal. PMID- 27181503 TI - Vesicoureteral Reflux and Antibiotic Prophylaxis: Why Cohorts and Methodologies Matter. AB - PURPOSE: Published cohorts of children with vesicoureteral reflux placed on antibiotic prophylaxis differ in baseline characteristics and methodology. These data have been combined in meta-analyses to derive treatment recommendations. We analyzed these cohorts in an attempt to understand the disparate outcomes reported. MATERIALS AND METHODS: A total of 18 studies were identified from 1987 to 2013. These series retrospectively or prospectively evaluated children with vesicoureteral reflux who were on long-term antibiotic prophylaxis. Presenting demographic data, criteria and methods of evaluation were tabulated. Outcomes were compared, specifically recurrent urinary infections and renal scarring. RESULTS: Significant differences identified in baseline characteristics included gender, circumcision status and reflux grade, and differences in methodology included evaluation of bowel and bladder dysfunction, method of urine collection, definition of urinary infection, measurement of compliance and means of identifying renal scarring. Cohorts with larger numbers of uncircumcised boys had more breakthrough urinary infections. Infection and renal scarring rates were higher in series with higher grades of reflux. Bagged urine specimens were allowed in 6 series, rendering the data suspect. Children with bowel and bladder dysfunction were excluded from 3 cohorts, and bowel and bladder dysfunction was correlated with outcome in only 1 cohort. Compliance was monitored in only 6 studies. CONCLUSIONS: Subpopulations and methodologies vary significantly in published series of children with vesicoureteral reflux on antibiotic prophylaxis. It is inappropriate to combine outcomes data from these series in a meta-analysis, which would serve to blur distinctions between these subpopulations. Broad recommendations or guidelines based on meta-analyses should be viewed with caution. PMID- 27181504 TI - Ten-Year Followup after Tension-Free Vaginal Tape-Obturator Procedure for Stress Urinary Incontinence. AB - PURPOSE: Suburethral tapes are a standard surgical treatment for stress urinary incontinence. The aim of the study was to evaluate subjective and objective cure rates 10 years after a tension-free vaginal tape-obturator procedure. MATERIALS AND METHODS: All 124 patients who underwent the tension-free vaginal tape obturator procedure at a total of 2 centers in 2004 and 2005 were invited for followup. Objective cure was defined as a negative cough stress test at 300 ml. Subjects completed KHQ (King's Health Questionnaire), IOQ (Incontinence Outcome Questionnaire), FSFI (Female Sexual Function Index Questionnaire) and PGI-I (Patient Global Impression of Improvement). RESULTS: Overall, 55 of 112 women (49%) who were alive were available for clinical examination and 71 (63%) completed the questionnaires. The objective cure rate in the 55 women examined clinically was 69%, 22% were not cured and 9% (5) had undergone reoperation for recurrent or persistent stress urinary incontinence. Treatment was counted as having failed in these 5 women for study purposes. Subjective cure was reported by 45 of 71 women (64%). Three patients (5%) had vaginal tape extrusion at the time of clinical examination. Extrusion in all of them was small and asymptomatic, and did not require treatment for a cumulative extrusion rate of 7%. Six women (9%) had undergone reoperation for tension-free vaginal tape obturator associated complications and 18 (26%) experienced de novo overactive bladder. CONCLUSIONS: Subjective and objective cure rates 10 years after the tension-free vaginal tape-obturator procedure were 69% and 64%, respectively. The vaginal extrusion rate in this study was slightly higher than in other series but major long-term complications appeared to be rare. PMID- 27181505 TI - Feasibility of a clinical trial to assess the effect of dietary calcium v. supplemental calcium on vascular and bone markers in healthy postmenopausal women. AB - Whether supplemental Ca has similar effects to dietary Ca on vascular and bone markers is unknown. The present trial investigated the feasibility of applying dietary and supplemental interventions in a randomised-controlled trial (RCT) aiming to estimate the effect of supplemental Ca as compared with dietary Ca on vascular and bone markers in postmenopausal women. In total, thirteen participants were randomised to a Ca supplement group (CaSuppl) (750 mg Ca from CaCO3+450 mg Ca from food+20 ug vitamin D supplement) or a Ca diet group (CaDiet) (1200 mg Ca from food+10 ug vitamin D supplement). Participants were instructed on Ca consumption targets at baseline. Monthly telephone follow-ups were conducted to assess adherence to interventions (+/-20 % of target total Ca) using the multiple-pass 24-h recall method and reported pill count. Measurements of arterial stiffness, peripheral blood pressure and body composition were performed at baseline and after 6 and 12 months in all participants who completed the trial (n 9). Blood and serum biomarkers were measured at baseline and at 12 months. Both groups were compliant to trial interventions (+/-20 % of target total Ca intake; pill count >=80 %). CaSuppl participants maintained a significantly lower average dietary Ca intake compared with CaDiet participants throughout the trial (453 (sd 187) mg/d v. 1241 (sd 319) mg/d; P<0.001). There were no significant differences in selected vascular outcomes between intervention groups over time. Our pilot trial demonstrated the feasibility of conducting a large-scale RCT to estimate the differential effects of supplemental and dietary Ca on vascular and bone health markers in healthy postmenopausal women. PMID- 27181506 TI - Solution structure of the isolated histone H2A-H2B heterodimer. AB - During chromatin-regulated processes, the histone H2A-H2B heterodimer functions dynamically in and out of the nucleosome. Although detailed crystal structures of nucleosomes have been established, that of the isolated full-length H2A-H2B heterodimer has remained elusive. Here, we have determined the solution structure of human H2A-H2B by NMR coupled with CS-Rosetta. H2A and H2B each contain a histone fold, comprising four alpha-helices and two beta-strands (alpha1-beta1 alpha2-beta2-alpha3-alphaC), together with the long disordered N- and C-terminal H2A tails and the long N-terminal H2B tail. The N-terminal alphaN helix, C terminal beta3 strand, and 310 helix of H2A observed in the H2A-H2B nucleosome structure are disordered in isolated H2A-H2B. In addition, the H2A alpha1 and H2B alphaC helices are not well fixed in the heterodimer, and the H2A and H2B tails are not completely random coils. Comparison of hydrogen-deuterium exchange, fast hydrogen exchange, and {(1)H}-(15)N hetero-nuclear NOE data with the CS-Rosetta structure indicates that there is some conformation in the H2A 310 helical and H2B Lys11 regions, while the repression domain of H2B (residues 27-34) exhibits an extended string-like structure. This first structure of the isolated H2A-H2B heterodimer provides insight into its dynamic functions in chromatin. PMID- 27181507 TI - Safety and immunogenicity of a CRM or TT conjugated meningococcal vaccine in healthy toddlers. AB - BACKGROUND: MenACWY-CRM (Menveo((r)); GlaxoSmithKline) and MenACWY-TT (Nimenrix((r)); Pfizer) are two meningococcal vaccines licensed in the European Union for use in both children and adults. While both vaccines target meningococcal serogroups A, C, W and Y, immunogenicity and reactogenicity of these quadrivalent meningococcal conjugate vaccines may differ due to differences in formulation processes and chemical structure. Yet data on the comparability of these two vaccines are limited. METHODS: The reactogenicity and immunogenicity of one dose of either MenACWY-CRM or MenACWY-TT were evaluated in healthy toddlers aged 12-15 months. Immunogenicity was assessed using serum bactericidal antibody assays (SBA) with human (hSBA) and rabbit (rSBA) complement. RESULTS: A total of 202 children aged 12-15 months were enrolled to receive one dose of MenACWY-CRM or MenACWY-TT. Similar numbers of subjects reported solicited reactions within 7 days following either vaccination. Tenderness at the injection site was the most common local reaction. Systemic reactions reported were similar for both vaccines and mostly mild to moderate in severity: irritability, sleepiness and change in eating habits were most commonly reported. Immunogenicity at 1 month post vaccination was generally comparable for both vaccines across serogroups. At 6 months post-vaccination antibody persistence against serogroups C, W, and Y was substantial for both vaccines, as measured by both assay methodologies. For serogroup A, hSBA titers declined in both groups, while rSBA titers remained high. CONCLUSION: Despite differences in composition, the MenACWY-CRM and MenACWY TT vaccines have comparable reactogenicity and immunogenicity profiles. Immediate immune responses and short-term antibody persistence were largely similar between groups. Both vaccines were well-tolerated and no safety concerns were identified. PMID- 27181508 TI - Increased risk of subclinical atherosclerosis associated with high visceral adiposity index in apparently healthy Korean adults: the Kangbuk Samsung Health Study. AB - BACKGROUND: The visceral adiposity index (VAI) is a mathematical tool that reflects a patient's visceral adiposity and insulin resistance. Recent studies have noted an association between VAI and cardiovascular event. We analyzed the association between VAI and coronary artery calcium score (CACS) in Korean adults. METHODS: For 33,468 participants (mean age 42 yrs) in a health screening program, VAI was calculated using the following formulae: [waist circumference (WC)/{39.68 + (1.88 * body mass index (BMI))}] * (triglyceride/1.03) * {1.31/high density lipoprotein cholesterol (HDL-C)} for men and [WC/{36.58 + (1.89 * BMI)}] * (triglyceride/0.81) * (1.52/HDL-C) for women. Coronary artery calcium scores were measured with multi-detector computed tomography. RESULTS: CACS was positively correlated with VAI (r = 0.027, p < 0.001). Subjects with 0 < CACS <100 and CACS >= 100 had significantly higher VAI compared to those with CACS = 0 (2.04 +/- 1.97, 2.08 +/- 1.67 vs. 1.68 +/- 1.50, p < 0.001). In logistic regression analyses with CACS >0 as the dependent variable, subjects in the highest tertile of VAI (>1.777) had significantly increased odds ratio for CACS >0 compared to subjects in the lowest tertile (<0.967), even after adjusting for confounding variables, including BMI (OR 1.26, 95% CI 1.147-1.381). CONCLUSIONS: Subjects with high VAI had increased risk for subclinical atherosclerosis, as assessed by CACS. Key messages Recent studies have noted an association between visceral adiposity index (VAI) and cardiovascular event. Subjects with coronary artery calcification (CAC) showed significantly higher VAI compared to those without CAC. The subjects with high VAI showed increased odds ratio for CAC as compared to subjects with low VAI, suggesting high VAI reflects increased risk for subclinical atherosclerosis. PMID- 27181509 TI - Transcranial direct current stimulation lessens dual task cost in people with Parkinson's disease. AB - BACKGROUND: Parkinson's disease (PD) progressively impairs motor and cognitive function. Gait dysfunction in PD is exacerbated during dual task gait. Transcranial direct current stimulation (tDCS) may therapeutically benefit motor and cognitive deficits. We examined the effect of a bilateral tDCS protocol on dual task gait in people with PD. MATERIAL AND METHODS: Participants with PD between 50 and 80 years received two sessions of tDCS protocol (1 active, 1 sham) separated by 7days. tDCS protocols were randomized and blinded to participants. After each tDCS protocol, participants performed single and dual task gait. Single 20-min session of bilateral tDCS (dorsolateral prefrontal cortex; left=anode, right=cathode) at 2mA and one sham session. Each participant was assessed at baseline for disease severity [Unified Parkinson's Disease Rating Scale (UPDRS)] and executive function [Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)]. Following each tDCS condition (active and sham), participants performed Timed Up and Go (TUG) single and dual task conditions (TUGalone, TUGmotor, TUGcognitive) and PDQ-39. RESULTS: Ten participants average age of 68.7 years (+/-10.2) and average PD duration average 7.9 years (+/-7.1) were included. The UPDRS (M=37) and RBANS (M=13%ile) were administered prior to testing. No differences were observed on dependent t-test for TUG conditions or PDQ-39. Dual task cost TUGmotor was -20.95% (tDCSactive) versus -22.58% (tDCSsham) and TUGcognitive was -25.24% (tDCSactive) versus 41.85% (tDCSsham). CONCLUSIONS: Our bilateral tDCS protocol in people with PD did not significantly improve dual task gait. However, dual task cost following tDCS was lessened, most dramatically in the presence of a cognitive distractor. A larger sample size is warranted to draw further conclusions about our bilateral tDCS approach. PMID- 27181511 TI - Curcumin ameliorates experimental autoimmune myasthenia gravis by diverse immune cells. AB - Curcumin is a traditional Asian medicine with diverse immunomodulatory properties used therapeutically in the treatment of many autoimmune diseases. However, the effects of curcumin on myasthenia gravis (MG) remain undefined. Here we investigated the effects and potential mechanisms of curcumin in experimental autoimmune myasthenia gravis (EAMG). Our results demonstrated that curcumin ameliorated the clinical scores of EAMG, suppressed the expression of T cell co stimulatory molecules (CD80 and CD86) and MHC class II, down-regulated the levels of pro-inflammatory cytokines (IL-17, IFN-gamma and TNF-alpha) and up-regulated the levels of the anti-inflammatory cytokine IL-10, shifted the balance from Th1/Th17 toward Th2/Treg, and increased the numbers of NKR-P1(+) cells (natural killer cell receptor protein 1 positive cells, including NK and NKT cells). Moreover, the administration of curcumin promoted the differentiation of B cells into a subset of B10 cells, increased the anti-R97-166 peptide IgG1 levels and decreased the relative affinity indexes of anti-R97-116 peptide IgG. In summary, curcumin effectively ameliorate EAMG, indicating that curcumin may be a potential candidate therapeutic agent for MG. PMID- 27181510 TI - Increased neuronal and astroglial aquaporin-1 immunoreactivity in rat striatum by chemical preconditioning with 3-nitropropionic acid. AB - Aquaporin-1 (AQP1) is a water channel expressed in the choroid plexus and participates in forming cerebrospinal fluid. Interestingly, reactive astrocytes also express AQP1 in the central nervous system under some pathological conditions. On the other hand, 3-nitropropionic acid (3NP) is a mitochondrial toxin that causes selective degeneration of striatum; however, its chemical preconditioning is neuroprotective against cerebral ischemia. We previously reported that mild 3NP application is accompanied with numerous reactive astrocytes in rat striatum devoid of typical necrotic lesions. Therefore, we studied whether AQP1 in the rat striatum could be upregulated with reactive astrocytosis using the 3NP model. Immunohistochemical or immunofluorescence analysis showed that reactive astrocytosis in the striatum, which upregulates glial fibrillary acidic protein and glutamine synthetase, was induced by mild doses of 3NP administration. Intriguingly, after 3NP treatment, AQP1 was intensely expressed not only by the subpopulation of astroglia but also by neurons. The AQP1 immunoreactivity became more intensified at the early-subtoxic stage (ES: 24-48h), but not as much in the delayed-subtoxic stage (DS: 96-120h). In contrast, AQP4 expression in the striatum was downregulated after 3NP treatment, in particular during the ES stage. AQP1 upregulation/AQP4 downregulation induced under subtoxic 3NP treatment may play a pivotal role in water homeostasis and cell viability in the striatum. PMID- 27181512 TI - Regulation of neural stem cells by choroid plexus cells population. AB - The choroid plexus is a tissue on the central nervous system responsible for producing cerebrospinal fluid, maintaining homeostasis and neural stem cells support; though, all of its functions still unclear. This study aimed to demonstrate the niches of choroid plexus cells for a better understanding of the cell types and functions, using the porcine as the animal model. The collected material was analyzed by histology, immunohistochemistry, and cell culture. The cell culture was characterizated by immunocytochemistry and flow cytometry. Our results showed OCT-4, TUBIII, Nestin, CD45, CD73, CD90 positive expression and GFAP, CD105 negative expression, also methylene blue histological staining confirmed the presence of telocytes cells. We realized that the choroid plexus is a unique and incomparable tissue with different niches of cells as pluripotent, hematopoietic, neuronal progenitors and telocyte cells, which provide its complexity, differentiated functionality and responsibility on brain balance and neural stem cells regulation. PMID- 27181513 TI - Psychotropic drugs attenuate lipopolysaccharide-induced hypothermia by altering hypothalamic levels of inflammatory mediators in rats. AB - Recent evidence suggests that inflammation may contribute to the pathophysiology of mental disorders and that psychotropic drugs exert various effects on brain inflammation. The administration of bacterial endotoxin (lipopolysaccharide, LPS) to mammals is associated with robust production of inflammatory mediators and pathological changes in body temperature. The objective of the present study was to examine the effects of four different psychotropic drugs on LPS-induced hypothermia and production of prostaglandin (PG) E2, tumor necrosis factor (TNF) alpha and phosphorylated-p65 (P-p65) levels in hypothalamus of LPS-treated rats. Rats were treated once daily with lithium (100mg/kg), carbamazepine (40mg/kg), haloperidol (2mg/kg), imipramine (20mg/kg) or vehicle (NaCl 0.9%) for 29 days. On day 29, rats were injected with LPS (1mg/kg) or saline. At 1.5h post LPS injection body temperature was measured, rats were sacrificed, blood was collected and their hypothalami were excised, homogenized and centrifuged. PGE2, TNF-alpha and nuclear P-p65 levels were determined by specific ELISA kits. We found that lithium, carbamazepine, haloperidol and imipramine significantly attenuated LPS-induced hypothermia, resembling the effect of classic anti inflammatory drugs. Moreover, lithium, carbamazepine, haloperidol and imipramine differently but significantly affected the levels of PGE2, TNF-alpha and P-p65 in plasma and hypothalamus of LPS-treated rats. The results suggest that psychotropic drugs attenuate LPS-induced hypothermia by reducing hypothalamic production of inflammatory constituents, particularly PGE2. The effects of psychotropic drugs on brain inflammation may contribute to their therapeutic mechanism but also to their toxicological profile. PMID- 27181514 TI - Red nucleus connectivity as revealed by constrained spherical deconvolution tractography. AB - Previous Diffusion Tensor Imaging studies have demonstrated that the human red nucleus is widely interconnected with sensory-motor and prefrontal cortices. In this study, we assessed red nucleus connectivity by using a multi-tensor model called non- negative Constrained Spherical Deconvolution (CSD), which is able to resolve more than one fiber orientation per voxel. Connections of the red nuclei of fifteen volunteers were studied at 3T using CSD axonal tracking. We found significant connectivity between RN and the following cortical and subcortical areas: cerebellar cortex, thalamus, paracentral lobule, postcentral gyrus, precentral gyrus, superior frontal gyrus and dentate nucleus. We confirmed that red nucleus is tightly linked with the cerebral cortex and has dense subcortical connections with thalamus and cerebellar cortex. These findings may be useful in a clinical context considering that RN is involved in motor control and it is known to have potential to compensate for injury of the corticospinal tract. PMID- 27181515 TI - Electroencephalography reactivity for prognostication of post-anoxic coma after cardiopulmonary resuscitation: A comparison of quantitative analysis and visual analysis. AB - Electroencephalogram reactivity (EEG-R) is a positive predictive factor for assessing outcomes in comatose patients. Most studies assess the prognostic value of EEG-R utilizing visual analysis; however, this method is prone to subjectivity. We sought to categorize EEG-R with a quantitative approach. We retrospectively studied consecutive comatose patients who had an EEG-R recording performed 1-3 days after cardiopulmonary resuscitation (CPR) or during normothermia after therapeutic hypothermia. EEG-R was assessed via visual analysis and quantitative analysis separately. Clinical outcomes were followed-up at 3-month and dichotomized as recovery of awareness or no recovery of awareness. A total of 96 patients met the inclusion criteria, and 38 (40%) patients recovered awareness at 3-month followed-up. Of 27 patients with EEG-R measured with visual analysis, 22 patients recovered awareness; and of the 69 patients who did not demonstrated EEG-R, 16 patients recovered awareness. The sensitivity and specificity of visually measured EEG-R were 58% and 91%, respectively. The area under the receiver operating characteristic curve for the quantitative analysis was 0.92 (95% confidence interval, 0.87-0.97), with the best cut-off value of 0.10. EEG-R through quantitative analysis might be a good method in predicting the recovery of awareness in patients with post-anoxic coma after CPR. PMID- 27181517 TI - Neuronal low-density lipoprotein receptor-related protein 1 (LRP1) enhances the anti-apoptotic effect of intravenous immunoglobulin (IVIg) in ischemic stroke. AB - The low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional and multi-ligand endocytic receptor abundantly expressed in neurons. Intravenous immunoglobulin (IVIg) is a purified preparation of plasma derived human immunoglobulin used for the treatment of several neurological inflammatory disorders, and proposed for the treatment of stroke for its potent neuroprotective effects. LRP1 has been shown to be involved in the transcytosis of IVIg, and IVIg-LRP1 interaction leads to LRP1 tyrosine phosphorylation, which may contribute to the anti-inflammatory effects of IVIg. However, the question remains whether IVIg could induce its neuroprotective effects via LRP1 in neurons under ischemic stroke conditions. In cultured neurons and in a transient ischemic mouse model, ischemia decrease LRP1 levels and phosphorylation, and IVIg blocks these effects. In ischemic neurons, LRP1 antagonism by receptor associated protein (RAP) enhances the activation of pro-death signaling pathways such as nuclear factor-kappa B (NF-kappaB), mitogen-activated protein kinases (MAPKs), and caspase-3, and IVIg reduces these effects. When applied to ischemic neuronal cultures, RAP induces a dramatic drop in Akt activation, and IVIg reverses this effect, as it does with the decrease in Bcl-2 levels caused by ischemic injury in the presence of RAP. Altogether, these results show evidence of LRP1 expression and activity modulation by IVIg, and support the role of LRP1 as a partner of IVIg in the execution of its neuroprotective effects. PMID- 27181516 TI - Enhancement of an outwardly rectifying chloride channel in hippocampal pyramidal neurons after cerebral ischemia. AB - Cerebral ischemia induces delayed, selective neuronal death in the CA1 region of the hippocampus. The underlying molecular mechanisms remain unclear, but it is known that apoptosis is involved in this process. Chloride efflux has been implicated in the progression of apoptosis in various cell types. Using both the inside-out and whole-cell configurations of the patch-clamp technique, the present study characterized an outwardly rectifying chloride channel (ORCC) in acutely dissociated pyramid neurons in the hippocampus of adult rats. The channel had a nonlinear current-voltage relationship with a conductance of 42.26+/-1.2pS in the positive voltage range and 18.23+/-0.96pS in the negative voltage range, indicating an outward rectification pattern. The channel is Cl(-) selective, and the open probability is voltage-dependent. It can be blocked by the classical Cl( ) channel blockers DIDS, SITS, NPPB and glibenclamide. We examined the different changes in ORCC activity in CA1 and CA3 pyramidal neurons at 6, 24 and 48h after transient forebrain ischemia. In the vulnerable CA1 neurons, ORCC activity was persistently enhanced after ischemic insult, whereas in the invulnerable CA3 neurons, no significant changes occurred. Further analysis of channel kinetics suggested that multiple openings are a major contributor to the increase in channel activity after ischemia. Pharmacological blockade of the ORCC partly attenuated cell death in the hippocampal neurons. We propose that the enhanced activity of ORCC might contribute to selective neuronal damage in the CA1 region after cerebral ischemia, and that ORCC may be a therapeutic target against ischemia-induced cell death. PMID- 27181518 TI - A pharmacological characterization of GABA, THIP and DS2 at binary alpha4beta3 and beta3delta receptors: GABA activates beta3delta receptors via the beta3(+)delta(-) interface. AB - There is growing evidence that GABA (gamma-aminobutyric acid) can activate GABAA receptors (GABAARs) in the absence of an alpha subunit. In this study, we compared the pharmacology of homomeric and binary alpha4, beta3 or delta subunits with ternary alpha4beta3delta to identify subunit interfaces that contribute to the pharmacology of GABA, THIP, and DS2, and the antagonists, Zn(2+), gabazine and bicuculline. beta3delta receptors form functional GABA-gated channels when expressed in Xenopus oocytes with a pharmacology that differs to homomeric beta3, binary alpha4beta3 and ternary alpha4beta3delta receptors. GABA had similar potency at alpha4beta3 and beta3delta receptors (25uM and 26uM, respectively) but differed at alpha4beta3delta receptors where GABA exhibited a biphasic concentration-response (EC50 (1)=12.6nM; EC50 (2)=6.3MUM). THIP activated beta3delta receptors (EC50=456MUM) but was a more potent activator of alpha4beta3 (EC50=27MUM) and alpha4beta3delta receptors (EC50 (1)=27.5nM; EC50 (2)=29.5MUMU), indicating that the alpha4 subunit significantly contribute to its potency. The delta-preferring modulator, DS2 had marginal or no effect at beta3delta and alpha4beta3 receptors, indicating a role for both the alpha4 and delta subunits for its potency. Gabazine inhibited GABA-elicited currents at beta3delta receptors whereas bicuculline activated these receptors. Mutational analysis verified that GABA binds to the beta3(+)delta(-) interface formed by the beta3 and delta subunits. In conclusion, evaluating agents against binary GABAARs such as beta3delta and alpha4beta3 receptors enables identification of interfaces that may contribute to the pharmacology of the more complex ternary alpha4beta3delta receptors. PMID- 27181520 TI - Arenediazonium salts as electrophiles for the oxidative addition of gold(i). AB - Arenediazonium salts generated in situ from anilines have been found for the first time to efficiently oxidize [AuCl(L)] (L = SMe2, PPh3) complexes in DMSO as a solvent, under thermal conditions. The structure of the [AuArCl2(L)] complexes formed has been confirmed by X-ray diffraction analyses. These complexes have been used as intermediates, in a one pot cross-coupling reaction of anilines with silver acetylides. PMID- 27181522 TI - Dynamic allocation and transfer of non-structural carbohydrates, a possible mechanism for the explosive growth of Moso bamboo (Phyllostachys heterocycla). AB - Moso bamboo can rapidly complete its growth in both height and diameter within only 35-40 days after shoot emergence. However, the underlying mechanism for this "explosive growth" remains poorly understood. We investigated the dynamics of non structural carbohydrates (NSCs) in shoots and attached mature bamboos over a 20 month period. The results showed that Moso bamboos rapidly completed their height and diameter growth within 38 days. At the same time, attached mature bamboos transferred almost all the NSCs of their leaves, branches, and especially trunks and rhizomes to the "explosively growing" shoots via underground rhizomes for the structural growth and metabolism of shoots. Approximately 4 months after shoot emergence, this transfer stopped when the leaves of the young bamboos could independently provide enough photoassimilates to meet the carbon demands of the young bamboos. During this period, the NSC content of the leaves, branches, trunks and rhizomes of mature bamboos declined by 1.5, 23, 28 and 5 fold, respectively. The trunk contributed the most NSCs to the shoots. Our findings provide new insight and a possible rational mechanism explaining the "explosive growth" of Moso bamboo and shed new light on understanding the role of NSCs in the rapid growth of Moso bamboo. PMID- 27181521 TI - Raising the avermectins production in Streptomyces avermitilis by utilizing nanosecond pulsed electric fields (nsPEFs). AB - Avermectins, a group of anthelmintic and insecticidal agents produced from Streptomyces avermitilis, are widely used in agricultural, veterinary, and medical fields. This study presents the first report on the potential of using nanosecond pulsed electric fields (nsPEFs) to improve avermectin production in S. avermitilis. The results of colony forming units showed that 20 pulses of nsPEFs at 10 kV/cm and 20 kV/cm had a significant effect on proliferation, while 100 pulses of nsPEFs at 30 kV/cm exhibited an obvious effect on inhibition of agents. Ultraviolet spectrophotometry assay revealed that 20 pulses of nsPEFs at 15 kV/cm increased avermectin production by 42% and reduced the time for reaching a plateau in fermentation process from 7 days to 5 days. In addition, the decreased oxidation reduction potential (ORP) and increased temperature of nsPEFs-treated liquid were evidenced to be closely associated with the improved cell growth and fermentation efficiency of avermectins in S. avermitilis. More importantly, the real-time RT-PCR analysis showed that nsPEFs could remarkably enhance the expression of aveR and malE in S. avermitilis during fermentation, which are positive regulator for avermectin biosynthesis. Therefore, the nsPEFs technology presents an alternative strategy to be developed to increase avermectin output in fermentation industry. PMID- 27181523 TI - One-pot conversion of disaccharide into 5-hydroxymethylfurfural catalyzed by imidazole ionic liquid. AB - Conversion of carbohydrate into 5-hydroxymethylfurfural (5- HMF), a versatile, key renewable platform compound is regarded as an important transformation in biomass-derived carbohydrate chemistry. A variety of ILs, not only acidic but also alkaline ILs, were synthesized and used as catalyst in the production of 5 HMF from disaccharide. Several factors including reaction temperature, IL dosage, solvent and reaction time,were found to influence the yield of 5-HMF from cellobiose. Of the ILs tested, hydroxy-functionalized ionic liquid (IL), 1 hydroxyethyl-3-methylimidazolium tetrafluoroborate ([AEMIM]BF4) showed the highest catalytic activity and selectivity. 5-HMF yield of 68.71% from sucrose was obtained after 6 hrs at 160 degrees C. At the same condition with cellobiose as substrate, 5-HMF yield was 24.73%. In addition, 5-HMF also exhibited good stablity in this reaction system. Moreover, a kinetic analysis was carried out in both acidic and alkaline IL-catalyzed system, suggesting main side reaction in the conversion of fructose catalyzed by acidic and alkaline IL was polymerization of fructose and 5-HMF degradation, respectively. PMID- 27181524 TI - Pancreatic differentiation of Pdx1-GFP reporter mouse induced pluripotent stem cells. AB - Efficient induction of defined lineages in pluripotent stem cells constitutes the determinant step for the generation of therapeutically relevant replacement cells to potentially treat a wide range of diseases, including diabetes. Pancreatic differentiation has remained an important challenge in large part because of the need to differentiate uncommitted pluripotent stem cells into highly specialized hormone-secreting cells, which has been shown to require a developmentally informed step-by-step induction procedure. Here, in the framework of using induced pluripotent stem cells (iPSCs) to generate pancreatic cells for pancreatic diseases, we have generated and characterized iPSCs from Pdx1-GFP transgenic mice. The use of a GFP reporter knocked into the endogenous Pdx1 promoter allowed us to monitor pancreatic induction based on the expression of Pdx1, a pancreatic master transcription factor, and to isolate a pure Pdx1-GFP+ population for downstream applications. Differentiated cultures timely expressed markers specific to each stage and end-stage progenies acquired a rather immature beta-cell phenotype, characterized by polyhormonal expression even among cells highly expressing the Pdx1-GFP reporter. Our findings highlight the utility of employing a fluorescent protein reporter under the control of a master developmental gene in order to devise novel differentiation protocols for relevant cell types for degenerative diseases such as pancreatic beta cells for diabetes. PMID- 27181519 TI - Stress granules at the intersection of autophagy and ALS. AB - Amyotrophic lateral sclerosis (ALS) is a progressive, fatal disease caused by loss of upper and lower motor neurons. The majority of ALS cases are classified as sporadic (80-90%), with the remaining considered familial based on patient history. The last decade has seen a surge in the identification of ALS-causing genes - including TARDBP (TDP-43), FUS, MATR3 (Matrin-3), C9ORF72 and several others - providing important insights into the molecular pathways involved in pathogenesis. Most of the protein products of ALS-linked genes fall into two functional categories: RNA-binding/homeostasis and protein-quality control (i.e. autophagy and proteasome). The RNA-binding proteins tend to be aggregation-prone with low-complexity domains similar to the prion-forming domains of yeast. Many also incorporate into stress granules (SGs), which are cytoplasmic ribonucleoprotein complexes that form in response to cellular stress. Mutant forms of TDP-43 and FUS perturb SG dynamics, lengthening their cytoplasmic persistence. Recent evidence suggests that SGs are regulated by the autophagy pathway, suggesting a unifying connection between many of the ALS-linked genes. Persistent SGs may give rise to intractable aggregates that disrupt neuronal homeostasis, thus failure to clear SGs by autophagic processes may promote ALS pathogenesis. This article is part of a Special Issue entitled SI:Autophagy. PMID- 27181525 TI - Geometric conductive filament confinement by nanotips for resistive switching of HfO2-RRAM devices with high performance. AB - Filament-type HfO2-based RRAM has been considered as one of the most promising candidates for future non-volatile memories. Further improvement of the stability, particularly at the "OFF" state, of such devices is mainly hindered by resistance variation induced by the uncontrolled oxygen vacancies distribution and filament growth in HfO2 films. We report highly stable endurance of TiN/Ti/HfO2/Si-tip RRAM devices using a CMOS compatible nanotip method. Simulations indicate that the nanotip bottom electrode provides a local confinement for the electrical field and ionic current density; thus a nano confinement for the oxygen vacancy distribution and nano-filament location is created by this approach. Conductive atomic force microscopy measurements confirm that the filaments form only on the nanotip region. Resistance switching by using pulses shows highly stable endurance for both ON and OFF modes, thanks to the geometric confinement of the conductive path and filament only above the nanotip. This nano-engineering approach opens a new pathway to realize forming-free RRAM devices with improved stability and reliability. PMID- 27181526 TI - Systematic review of qualitative and quantitative studies on the attitudes and barriers to percutaneous endoscopic gastrostomy feeding. AB - BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is now commonly used in long-term care and community settings. However, regional variations exist in the acceptability of PEG tube feeding with long-term nasogastric feeding still commonplace in many Asian nations. AIMS: To evaluate the evidence relating to attitudes towards PEG feeding and to determine potential barriers to the acceptance of PEG tube feeding. METHODS: We searched Ovid MEDLINE, EMBASE, the Cochrane Library, Web of Science and CINAHL databases. The search for the studies was performed without restrictions by using the terms "PEG", "percutaneous endoscopic gastrostomy", "enteral feeding", "attitude", "perception" and "opinion". Qualitative and quantitative studies were included. Quality of studies was assessed with the Alberta checklists. RESULTS: From 981 articles, 17 articles were included in the final analysis. Twelve qualitative and four quantitative studies were considered of good quality. Seven of the 14 studies reported positive attitudes towards PEG. Three major themes were identified in terms of barriers to PEG feeding: lack of choice (poor knowledge, inadequate competency and skills, insufficient time given, not enough information given, lack of guidelines or protocol, resource constraints), confronting mortality (choosing life or death, risk of procedure) and weighing alternatives (adapting lifestyle, family influences, attitudes of healthcare professionals (HCPs), fear and anxiety). CONCLUSIONS: Only half of the reviewed studies reported positive perceptions towards PEG feeding. The themes identified in our systematic review will guide the development of interventions to alter the current attitudes and barriers towards PEG tube feeding. PMID- 27181527 TI - Body mass index and fat mass by skin-fold thickness are good predictors for body fat composition change by dual-energy x-ray absorptiometry in obesity adolescent. PMID- 27181528 TI - Increase in Endoscopic and Laparoscopic Surgery Regarding the Therapeutic Approach of Gastric Cancer Detected by Cancer Screening in Saga Prefecture, Japan. AB - Objective Despite recent advances in endoscopic treatment and laparoscopic surgery for gastric cancers, an increase in the uptake of these therapeutic approaches has not yet been fully demonstrated. Therefore, the present study aimed to investigate the change in therapeutic approaches regarding the treatment of gastric cancers detected by cancer screening in Saga Prefecture, Japan between April 2002 and March 2011. Methods Gastric cancer screening by X-ray was performed on 311,074 subjects between April 2002 and March 2011. In total, 534 patients were thereafter diagnosed with gastric cancer. Eighteen subjects were excluded because precise details of their treatment were not available. To evaluate the changes in the therapeutic approach, the observation period was divided into three 3-year intervals: Period I: April 2002 to March 2005; Period II: April 2005 to March 2008; Period III: April 2008 to March 2011. Results The use of open laparotomy for the treatment of gastric cancer decreased, and laparoscopic surgery and endoscopic treatment increased markedly in a time dependent manner. A 2.5-fold increase in endoscopic treatment, and a 18.4-fold increase in laparoscopic surgery were observed in Period III compared with Period I (after adjusting for age and tumor characteristics). Conclusion Endoscopic treatment and laparoscopic surgery for gastric cancer increased during the investigation period (2002-2011), although the tumor characteristics of the gastric cancers detected through cancer screening in Saga Prefecture, Japan did not show any changes. PMID- 27181529 TI - Dissociation between Low Vitamin D Level and Hypertension in Coal Mine Workers: Evidence from the Kailuan Study. AB - Objective The aim of this study was to evaluate the vitamin D status and the relationship between the vitamin D status and hypertension in a relatively large cohort in northern China. Methods This study was a part of the Kailuan study, consisting of 3,788 coal mine workers (including 2,532 underground workers and 1,256 surface workers) who received periodic health examinations between September 13, 2012 and December 24, 2012. Information on demographic factors, personal history and medical history were collected. The height, weight, blood pressure and serum25-hydroxyvitamin D [25(OH)D] level of each patient were measured. Results The mean 25(OH)D level in this cohort was 21.73+/-15.82 nmol/L. The number (%) of patients with vitamin D deficiency, insufficiency, inadequacy and sufficiency were 2,509 (66.24%), 1,051 (27.75%), 201 (5.31%) and 27 (0.71%), respectively. In all the participants, after adjusting for the age, salt intake, physical activity, smoking status, alcohol drinking status, work type, work environment, body mass index, diabetes and hyperlipidemia, the odds ratios for hypertension with 25(OH)D level >=50, 25-50 and <25 nmol/L were 1.00 (reference), 1.44 (95%CI, 0.99-2.11) and 1.39 (95%CI, 0.97-1.99), respectively. Logistic regression models to evaluate the odds ratios and 95% CIs of hypertension for each quintile of the 25(OH)D level did not determine significant associations between the vitamin D status and hypertension. No significant associations were found in the underground workers or in the surface workers. Conclusion There was a high proportion of coal mine workers with vitamin D deficiency and insufficiency in Kailuan. However, no significant association between low vitamin D levels and hypertension was found in this cohort. Further investigations are needed to determine the relationship between vitamin D levels and hypertension. PMID- 27181530 TI - Interrelationship between the Myocardial Mass, Fibrosis, BNP, and Clinical Outcomes in Hypertrophic Cardiomyopathy. AB - Objective Increased left ventricular mass (LVM) and LV fibrosis mass (LVFM) are characteristics of hypertrophic cardiomyopathy (HCM). Additionally, a substantial increase in the plasma B-type natriuretic peptide (BNP) level is observed. Therefore, we investigated the interrelationship and clinical significances of these parameters in a HCM cohort that underwent cardiac MRI (CMR). Methods Patients with HCM (n=109) receiving regular outpatient treatment underwent CMR and follow-up through 2015 from CMR examinations. The clinical outcome measures were all-cause mortality, admission for worsening heart failure, and ventricular tachycardia/fibrillation. Results The baseline body mass index (BMI), LV outflow tract (LVOT) obstruction, New York Heart Association (NYHA) class, and increased left atrial dimension (LAD) index were associated with the plasma BNP level. In the CMR analysis, LVM and LVFM indices significantly correlated with the BNP level (r=0.422 and 0.368, respectively), which were independent determinants according to a multivariate analysis (p=0.009 and 0.023, respectively). A Kaplan Meier analysis during a median follow-up of 19.4 months showed that the baseline LVM or LVFM index was not associated with the clinical outcomes. However, the baseline BNP level was significantly associated with them (p<0.001). In addition, a multivariate Cox proportional hazard analysis showed that plasma BNP was an independent predictor for the clinical outcomes after adjusting for age, sex, LVM, and LVFM. Conclusion The LVM and LVFM are determinants of the BNP level independent of the BMI, LVOT obstruction, LAD, and NYHA class in patients with HCM. However, plasma BNP may be a more sensitive integrated-marker for the clinical outcomes than LVM or LVFM. PMID- 27181531 TI - Sex Differences in the Association between the Eicosapentaenoic Acid/Arachidonic Acid Ratio and the Visceral Fat Area among Patients with Type 2 Diabetes. AB - Objective To examine the serum levels of eicosapentaenoic acid (EPA) and the ratios of docosahexaenoic acid (DHA), and the EPA/arachidonic acid (AA) and DHA/AA and to clarify their association with the areas of subcutaneous and visceral fat separately by sex among patients with type 2 diabetes. Methods The study participants included 118 men and 96 women who were hospitalized to receive treatment for type 2 diabetes. We examined the serum levels of EPA and DHA and the ratios of EPA/AA and DHA/AA, and analyzed their association with the total fat area (TFA), subcutaneous fat area (SFA), and visceral fat area (VFA), as measured by computed tomography. Results The mean age of the study participants was 62.6+/-13.6 years. The mean HbA1c level was 9.37+/-2.27%. Among men, a multivariate regression analysis adjusted for age and BMI, revealed a significant negative association between VFA and the EPA/AA ratio. When the multivariate regression analysis was adjusted for age, BMI, and HbA1c level, VFA was still found to be significantly negatively associated with the EPA/AA ratio. Although a crude analysis revealed a significant negative association between SFA and the EPA/AA ratio in women, no association was observed in multivariate regression analyses. Conclusion These results suggest the possibility that EPA inhibits the accumulation of visceral fat in men. Furthermore, there appear to be marked differences in the relationships between EPA and DHA and visceral fat accumulation. PMID- 27181532 TI - Long-term Efficacy and Safety of Sitagliptin in Elderly Patients with Type 2 Diabetes Mellitus. AB - Objective We herein conducted a retrospective study to evaluate the long-term efficacy and safety of sitagliptin treatment in elderly patients with type 2 diabetes mellitus. Methods We analyzed the changes in glycemic control in 112 Japanese type 2 diabetes patients over 65 years of age treated with 50 mg/day sitagliptin. Hemoglobin A1c (HbA1c) levels, liver and kidney functions, and usage of hypoglycemic agents were recorded for 24 months. Results HbA1c levels were significantly decreased, and the significance of HbA1c reduction was maintained during the observation period [from 7.7+/-1.1% to 7.2+/-0.7% (p<0.001) at the end of observational period]. The %change in HbA1c levels was significantly and negatively correlated with the baseline HbA1c levels (r=-0.51, p<0.001), but not with age, duration of diabetes, or the estimated glomerular filtration rate (eGFR). No patient experienced severe hypoglycemia episodes, and aspartate transaminase, alanine transaminase, gamma-glutamyl transpeptidase, and the eGFR remained unchanged. The dose of sulfonylurea was finally decreased in 72% of patients treated with sulfonylurea. Conclusion Sitagliptin treatment continually decreases the HbA1c level for 24 months and is useful to reduce the dose of sulfonylurea in elderly patients with type 2 diabetes. PMID- 27181533 TI - The Diagnostic Value of Circulating Brain-specific MicroRNAs for Ischemic Stroke. AB - Objective Circulating microRNAs have been recognized as promising biomarkers for various diseases. The aim of the present study was to explore the potential role of circulating miR-107, miR-128b and miR-153 as non-invasive biomarkers in the diagnosis of ischemia stroke. Methods One hundred and fourteen ischemic stroke patients (61+/-11.3 years old) and 58 healthy volunteers (56+/-3.9 years old) matched for age and sex were enrolled in this study. Total RNA was isolated from plasma with TRIzol reagent. The circulating microRNAs levels were measured by quantitative real-time polymerase chain reaction. Results The circulating levels of miR-107, miR-128b and miR-153 significantly increased 2.78-, 2.13- and 1.83 fold in ischemia stroke patients in comparison to the healthy volunteers, respectively. Receiver operating characteristic (ROC) curves were analyzed using the SPSS software program and revealed the areas under the curve for circulating miR-107, miR-128b and miR-153 to be 0.97, 0.903 and 0.893 in ischemia stroke patients in comparison to healthy volunteers, respectively. The levels of circulating miR-107, miR-128b and miR-153 therefore positively correlated with the severity of stroke as defined by NIHSS classes. Conclusion Our results suggest that circulating miR-107, miR-128b and miR-153 might be used as potential novel non-invasive biomarkers for the diagnosis of ischemia stroke. However, future prospective trials in large-sized patient cohorts are needed before drawing any definitive conclusions. PMID- 27181534 TI - Cessation of In-line Filters in Central Venous Catheters Does Not Significantly Influence the Incidence of Bloodstream Infections and Mortality in a Hospital Hematological Ward. AB - Objective The use of intravenous in-line filters is effective for the mechanical removal of large particles, precipitates, bacteria, fungi, large lipid globules, and air. However, the routine use of in-line filters remains controversial. Many patients with hematological diseases frequently suffer from bloodstream infections (BSIs) with fatal outcomes. Methods The year before cessation of an in line filter was defined as the "filter period" and the year after its cessation was defined as the "non-filter period." The number of central line-associated bloodstream infections (CLABSIs), which are defined through surveillance, the catheter utilization rate, the number of patient deaths within 7 days after removal of the central venous catheters (CVCs), and the overall survival rate following CVC insertion were measured. Results During both periods, 84 patients had a total of 140 CVCs with a total number of catheter days of 3,407. There were 10 CVCs with CLABSIs, and the overall CLABSI rate was 2.9/1,000 catheter days, including 4 CVCs with CLABSIs (2.5/1,000 catheter days) during the filter period and 6 CVCs with CLABSIs (3.3/1,000 catheter days) during the non-filter period. The CLABSI rate, catheter utilization rate, and mortality did not differ significantly between the two periods. The only independent variable that was found to be significantly associated with the development of CLABSIs was a neutrophil count of <500*10(6)/L (p<0.05). Conclusion Our study revealed that the cessation of in-line filters from CVCs does not significantly influence the incidence of BSIs and mortality in patients with hematological disease. To confirm our results, however, a large-scale randomized controlled study is warranted. PMID- 27181535 TI - Over-the-counter Drug Induced Autoimmune Hepatitis. AB - A 64-year-old man seeking treatment for a common cold was admitted to our hospital due to symptoms of general fatigue and liver dysfunction. A thorough history review revealed that the patient had recently started taking an over-the counter (OTC) drug. Drug-induced lymphocyte stimulation tests were positive. Serum markers for autoimmune hepatitis (AIH) were particularly elevated. Liver biopsy revealed spotty necrosis and ceroid-pigmented Kupffer cells and piecemeal necrosis with multiple plasma cells. He responded to corticosteroids, thus suggesting the presence of an immune-mediated component associated with the liver injury. Liver injury after using OTCs should be included in the differential diagnosis for chronic hepatitis with features of AIH. PMID- 27181536 TI - Internal Mammary Artery Injury Related to Chest Compressions in a Patient with Post-cardiac Arrest Syndrome. AB - Although high-quality cardiopulmonary resuscitation (CPR) is essential for survival from cardiac arrest, chest compressions can also sometimes lead to life threatening chest injuries. In addition, post-cardiac arrest syndrome patients often have coagulopathy due to therapeutic hypothermia, mechanical hemodynamic support, or both. Therefore, when progressive anemia and prolonged shock are detected in patients who have received CPR, identifying the cause of hemorrhagic shock is crucial. We herein present an interesting case of hemorrhagic shock due to an internal mammary artery injury secondary to CPR that was detected by computed tomography and invasive angiography. PMID- 27181537 TI - Ruptured Right Sinus of Valsalva Aneurysm Caused by Suspected Takayasu's Arteritis. AB - A sinus of Valsalva aneurysm (SVA) is a rare aortic anomaly. The most common complication is a rupture into the right ventricle and atrium. An SVA rupture into the left ventricle is a rare event. A 42-year-old man visited an outpatient clinic due to worsening exertional dyspnea. A loud to-and-fro heart murmur was detected, and echocardiography revealed a right SVA that had ruptured into the left ventricle, inducing acute heart failure. Computed tomography imaging allowed us to determine that the right SVA had been caused by asymptomatic Takayasu's arteritis. The patient was treated with prednisolone and the right SVA rupture was surgically repaired. PMID- 27181539 TI - Late Metabolic Acidosis Caused by Renal Tubular Acidosis in Acute Salicylate Poisoning. AB - A 16-year-old man was transferred to our emergency department seven hours after ingesting 486 aspirin tablets. His blood salicylate level was 83.7 mg/dL. He was treated with fluid resuscitation and sodium bicarbonate infusion, and his condition gradually improved, with a decline in the blood salicylate level. However, eight days after admission, he again reported nausea, a venous blood gas revealed metabolic acidosis with a normal anion gap. The blood salicylate level was undetectable, and a urinalysis showed glycosuria, proteinuria and elevated beta-2 microglobulin and n-acetyl glucosamine levels, with a normal urinary pH despite the acidosis. We diagnosed him with relapse of metabolic acidosis caused by renal tubular acidosis. PMID- 27181538 TI - Hypoglycemia Associated with a Gastrointestinal Stromal Tumor Producing High molecular-weight Insulin Growth Factor II: A Case Report and Literature Review. AB - A 61-year-old woman with multiple metastatic and unresectable gastrointestinal stromal tumors (GISTs) was referred for investigation of refractory hypoglycemia that developed four months before this hospitalization. On admission, her fasting plasma glucose was 38 mg/dL despite 10% glucose infusion. Investigations revealed that her serum C-peptide, insulin and growth hormone levels were suppressed, and big insulin-like growth factor II was observed. She was diagnosed with non-islet cell tumor hypoglycemia, which resolved after glucocorticoid treatment. Clinicians should thus be vigilant to identify hypoglycemia in patients with large metastatic GISTs because glucocorticoid therapy is useful even if the GIST is inoperable. PMID- 27181540 TI - Light Chain Deposition Disease in an Older Adult Patient Successfully Treated with Long-term Administration of Bortezomib, Melphalan and Prednisone. AB - A 70-year-old woman was admitted to our hospital because of fatigue and renal dysfunction and was diagnosed with light chain deposition disease (LCDD) with multiple organ involvement (kidney, thyroid gland, heart and eyes). After chemotherapy with bortezomib, cyclophosphamide and dexamethasone, hepatobiliary enzyme levels increased abruptly. A liver biopsy showed light chain deposition in Disse spaces. After two years of treatment with bortezomib, melphalan and prednisone (VMP) administered at shorter intervals relative to regular cycles, the patient showed a hematological and organ response. This case indicates that a relatively low dose intensity VMP regimen is preferable for elderly patients with LCDD with multiple organ involvement. PMID- 27181541 TI - Infected Aneurysm after Endoscopic Submucosal Dissection. AB - A 79-year-old man on hemodialysis was hospitalized for further investigation. Early gastric cancer was diagnosed by gastrointestinal endoscopy and endoscopic submucosal dissection (ESD) was performed. Fever and abdominal pain thereafter developed, and a severe inflammatory response was observed on a blood test. Contrast computed tomography (CT) showed ulcer-like projections and soft tissue surrounding the aorta, from the celiac to left renal artery. An infected aneurysm was diagnosed. Although infected aneurysms developing after laparoscopic cholecystectomy or biopsy of contiguous esophageal duplication cyst have been reported, those developing after ESD have not. When fever and abdominal pain develop after ESD, an infected aneurysm should be considered and contrast CT performed. PMID- 27181542 TI - Concomitant Systemic Sclerosis and Sarcoidosis with Combined Pulmonary Fibrosis and Emphysema. AB - A 75-year-old woman was referred to our hospital with the chief symptom of dyspnea. Chest computed tomography revealed lymphadenopathy, emphysema, and honeycombing. Sarcoidosis was diagnosed due to an elevated serum ACE level and the findings of a lymph-node biopsy. Her smoking history, radiography findings, and impaired gas exchange indicated combined pulmonary fibrosis and emphysema (CPFE). Raynaud's phenomenon gradually appeared, and we also diagnosed her with systemic sclerosis (SSc). Right heart catheterization revealed pulmonary hypertension (PH). Smoking was assumed to be the chief cause, but SSc may also induce the development of CPFE. Severe PH induced by CPFE or SSc was present, but the influence of sarcoidosis also could not be ignored. PMID- 27181543 TI - Small-cell Lung Cancer in a Young Adult Nonsmoking Patient with Ectopic Adrenocorticotropin (ACTH) Production. AB - Cushing's syndrome due to young small-cell lung cancer (SCLC) is recognized as being extremely rare. We herein present the case of a 35-year-old nonsmoking man who presented with thirst and polyuria. Laboratory examinations showed hyperglycemia, hypokalemia and liver enzyme elevation. Imaging examinations revealed the presence of multiple liver tumors and lymph node swelling. The levels of serum neuroendocrine tumor markers were elevated. The patient was diagnosed with SCLC based on the pathological examination of a biopsy specimen from the right supraclavicular lymph node. The physical findings, including proximal myopathy, truncal obesity and pigmentation suggested high levels of glucocorticoids. An immunohistochemical examination of the tumor showed that it was positive for adrenocorticotropin (ACTH). An endocrinological investigation allowed for the definitive diagnosis of SCLC with ectopic ACTH production. PMID- 27181544 TI - Elevation of the Hepatitis B Virus DNA during the Treatment of Polycythemia Vera with the JAK Kinase Inhibitor Ruxolitinib. AB - Ruxolitinib is a useful treatment option for myelofibrosis since it effectively resolves splenomegaly and constitutional symptoms. After the widespread use of ruxolitinib outside of clinical trials, a series of case reports indicated a potential risk of ruxolitinib-associated opportunistic infections, including the reactivation of the hepatitis B virus (HBV). We herein report the case of a polycythemia vera patient who showed an elevation of HBV-DNA viral DNA with an elevation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) after the initiation of ruxolitinib. Anti-viral therapy with entecavir was immediately started and the HBV viral load thereafter decreased with an improvement of the liver function. Physicians should thus be aware of the potential risk of ruxolitinib-associated HBV reactivation. PMID- 27181545 TI - Recurrence of Psoriasis Vulgaris Accompanied by Treatment with C-C Chemokine Receptor Type 4 (CCR4) Antibody (Mogamulizumab) Therapies in a Patient with Adult T cell Leukemia/ Lymphoma: Insight into Autoinflammatory Diseases. AB - Adult T cell leukemia / lymphoma (ATL) is one of the most aggressive hematological malignancies caused by human T-lymphotropic virus type-I (HTLV-1). Mogamulizumab is a new defucosylated humanized monoclonal antibody agent which targets C-C chemokine receptor type 4 (CCR4) expressed occasionally on the surface of ATL cells. However, adverse events such as drug eruptions have also been highlighted, at least in part, via the dysfunction of regulatory T cells (Tregs). We herein report a pronounced recurrence of systemic psoriasis vulgaris accompanied by the treatment of mogamulizumab in a patient with ATL. Pathological examinations may suggest a mechanistic link between the recurrence of autoinflammatory diseases and anti-CCR4 antibody therapies. PMID- 27181546 TI - Anti-myelin Oligodendrocyte Glycoprotein Antibodies in a Patient with Recurrent Optic Neuritis Involving the Cerebral White Matter and Brainstem. AB - We herein report a case of recurrent optic neuritis involving the cerebral white matter and brainstem in a patient positive for anti-myelin oligodendrocyte glycoprotein (MOG) antibodies. The patient had an initial attack at 24 years of age. Optic neuritis recurred over 14 years, and she was admitted to our neurology unit at 38 years of age. She showed bilateral optic neuritis, high-intensity lesions in the cerebral white matter and brainstem on T2 MRI with contrast enhancement, and elevated serum anti-MOG antibodies. Immunotherapy improved the MRI lesions. Recurrent optic neuritis in patients with anti-MOG antibodies may thus involve the cerebral white matter and brainstem. PMID- 27181547 TI - IgG4-Related Sialoadenitis with a Skin Lesion and Multiple Mononeuropathies Suggesting Coexistent Cryoglobulinemic Vasculitis. AB - A 68-year-old man was admitted because of weakness of the left leg, dysesthesiae of the extremities and bilateral lower extremity purpura. A neurological examination showed mononeuritis multiplex with laboratory evidence of hypocomplementemia, cryoglobulinemia and leukocytoclastic vasculitis in the biopsy of a skin specimen. The patient also exhibited bilateral submandibular gland swelling, elevated serum IgG4 levels and infiltration of a large number of IgG4-positive plasma cells in the submandibular glands. These findings were consistent with both cryoglobulinemic vasculitis and IgG4-related disease. The administration of oral prednisolone (1 mg/kg/day) resolved the neurological manifestations and the swelling of the submandibular glands and cryoglobulinemia. PMID- 27181548 TI - Relapsing Polychondritis Complicated by Vasculitis of the Omentum. AB - A 78-year-old man presented with bilateral auricular and nasal chondritis and an inner ear disorder. Relapsing polychondritis (RPC) was diagnosed and corticosteroid therapy was initiated. Two years later, he developed abdominal pain and a fever. A contrast-enhanced computed tomography scan showed enhancement of the mesentery and massive ascites. The patient underwent emergency laparotomy, which revealed inflammation and thickening of the omentum. A microscopic examination of the omentum disclosed vasculitis, and corticosteroid and cyclophosphamide pulse therapies were administered. We herein report the first case of RPC complicated by pathologically proven vasculitis of the omentum, clearly indicating an association between the pathogenesis of these two conditions. PMID- 27181549 TI - Acute Tubulointerstitial Nephritis Associated with Infliximab in a Patient with Crohn's Disease. AB - We report the findings of a 46-year-old man, who presented with fever and renal dysfunction while undergoing treatment for Crohn's disease with infliximab (IFX). Remittent fever and renal dysfunction with urinary casts developed and lasted for 3 weeks without deterioration of Crohn's disease. Renal biopsy revealed acute tubulointerstitial nephritis (ATIN). After the discontinuation of IFX, his fever and renal abnormalities resolved. We herein report the first known case of ATIN associated with IFX. PMID- 27181550 TI - Hepatitis B Virus Reactivation Following Salazosulfapyridine Monotherapy in a Patient with Rheumatoid Arthritis. AB - A 72-year-old man was diagnosed with rheumatoid arthritis (RA) and prior hepatitis B virus (HBV) infection. He began treatment with salazosulfapyridine (SASP). Several months later, his blood tests reflected a slightly elevated liver function. Serum tests were positive for hepatitis B surface antigen and HBV-DNA, and the diagnosis of de novo HBV hepatitis was made. A genetic analysis showed that he had polymorphisms of ABCG2 and NAT2, which could lead to high plasma concentrations of SASP and sulfapyridine. To the best of our knowledge, this is the first report of de novo hepatitis developing during SASP monotherapy for RA. PMID- 27181551 TI - Successful Treatment with Adalimumab for Intestinal Behcet's Disease during Pregnancy. AB - A 36-year-old Japanese woman with intestinal Behcet's disease was admitted to our hospital due to a recurrent ileocecal ulcer. Because infliximab (IFX) showed secondary failure, IFX was switched to adalimumab (ADA). After the third injection of ADA, she was unexpectedly 4-weeks pregnant. ADA was continued until 20 gestational weeks. Remission of the disease activity was maintained during pregnancy, and the birth was uneventful. The ileocecal ulcer disappeared after her delivery. ADA was detected in the umbilical blood after 119 days from the last infusion. The placental transition and timing of neonatal vaccination should be considered in cases of pregnancy with TNF antibody therapy. PMID- 27181552 TI - A False Positive Dengue Fever Rapid Diagnostic Test Result in a Case of Acute Parvovirus B19 Infection. AB - An outbreak of dengue fever occurred in Japan in August 2014. We herein report the case of a 63-year-old man who presented with a persistent fever in September 2014. Acute parvovirus B19 infection led to a false positive finding of dengue fever on a rapid diagnostic test (Panbio Dengue Duo Cassette(TM)). To the best of our knowledge, there are no previous reports of a false positive result for dengue IgM with the dengue rapid diagnostic test. We believe that epidemiological information on the prevalence of parvovirus B19 is useful for guiding the interpretation of a positive result with the dengue rapid diagnostic test. PMID- 27181553 TI - CD8 Encephalitis Caused by Persistently Detectable Drug-resistant HIV. AB - We herein report a 52-year-old man infected with human immunodeficiency virus (HIV) who was referred to our hospital due to the development of severe neurocognitive disorders and bilateral leukoencephalopathy. He has been treated with antiretroviral agents for 17 years, but low-level viremia has been detected consistently prior to admission. Drug resistant testing of the serum and the cerebrospinal fluid (CSF) both demonstrated a M184V mutation. A brain biopsy revealed perivascular CD8(+) T-lymphocyte infiltration, leading to the diagnosis of CD8 encephalitis. The clinical symptoms improved drastically after changing to a nucleoside reverse transcriptase inhibitor sparing regimen, which subsequently decreased the HIV viral load to an undetectable level in both the serum and CSF. PMID- 27181554 TI - Overlap of IgG4-related Disease and Primary Biliary Cirrhosis Complicated with Autoimmune Thrombocytopenia. AB - A 63-year-old woman was referred to Fukushima Red Cross Hospital with an enlargement of the left submandibular gland and subcutaneous bleeding in the chest and legs. A diffuse enlargement of the pancreas was also detected by abdominal computed tomography, and laboratory data showed severe thrombocytopenia. She was diagnosed with IgG4-related disease (IgG4-RD) complicated with autoimmune thrombocytopenia and was treated with methylprednisolone, after which the number of platelets favorably increased. Further investigation for liver dysfunction revealed underlying primary biliary cirrhosis (PBC). We herein report a rare case of IgG4-RD overlapping PBC complicated with autoimmune thrombocytopenia. PMID- 27181556 TI - Pulmonary Artery Intimal Sarcoma Invading the Left Lung. PMID- 27181555 TI - Autoimmune Limbic Encephalitis and Syndrome of Inappropriate Antidiuretic Hormone Secretion Associated with Lamotrigine-induced Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) Syndrome. AB - Drug rash with eosinophilia and systemic symptoms (DRESS) is a severe drug hypersensitivity reaction characterized by rash, fever and multi-organ failure. Limbic encephalitis (LE) is a rare disorder characterized by cognitive dysfunction with memory disturbance, seizures and psychiatric symptoms. We herein present an unusual case of DRESS syndrome due to lamotrigine with reactivation of Epstein-Barr virus, which developed autoimmune LE and syndrome of inappropriate antidiuretic hormone secretion. Discontinuation of lamotrigine, administration of methylprednisolone and intravenous immunoglobulin led to improvement. The LE in this case might have been caused by an autoimmune inflammatory mechanism associated with DRESS syndrome. PMID- 27181557 TI - Lipoid Pneumonia with Partial Anomalous Pulmonary Venous Return. PMID- 27181558 TI - Fever and Pulmonary Shadows in a Young Woman. PMID- 27181559 TI - Intraorbital Granuloma in Granulomatosis with Polyangiitis. PMID- 27181560 TI - Should Inflammatory Markers Be Used in the Diagnosis of a Fever of Unknown Origin? PMID- 27181561 TI - Should Inflammatory Markers Be Used in the Diagnosis of a Fever of Unknown Origin? PMID- 27181562 TI - The protozoan nucleus. AB - The nucleus is arguably the defining characteristic of eukaryotes, distinguishing their cell organisation from both bacteria and archaea. Though the evolutionary history of the nucleus remains the subject of debate, its emergence differs from several other eukaryotic organelles in that it appears not to have evolved through symbiosis, but by cell membrane elaboration from an archaeal ancestor. Evolution of the nucleus has been accompanied by elaboration of nuclear structures that are intimately linked with most aspects of nuclear genome function, including chromosome organisation, DNA maintenance, replication and segregation, and gene expression controls. Here we discuss the complexity of the nucleus and its substructures in protozoan eukaryotes, with a particular emphasis on divergent aspects in eukaryotic parasites, which shed light on nuclear function throughout eukaryotes and reveal specialisations that underpin pathogen biology. PMID- 27181563 TI - Dietary patterns and sociodemographic factors: considerations for nutrition research. PMID- 27181564 TI - Regression coefficient-based scoring system should be used to assign weights to the risk index. AB - OBJECTIVE: Some previously developed risk scores contained a mathematical error in their construction: risk ratios were added to derive weights to construct a summary risk score. This study demonstrates the mathematical error and derived different versions of the Charlson comorbidity score (CCS) using regression coefficient-based and risk ratio-based scoring systems to further demonstrate the effects of incorrect weighting on performance in predicting mortality. STUDY DESIGN AND SETTING: This retrospective cohort study included elderly people from the Clinical Practice Research Datalink. Cox proportional hazards regression models were constructed for time to 1-year mortality. Weights were assigned to 17 comorbidities using regression coefficient-based and risk ratio-based scoring systems. Different versions of CCS were compared using Akaike information criteria (AIC), McFadden's adjusted R2, and net reclassification improvement (NRI). RESULTS: Regression coefficient-based models (Beta, Beta10/integer, Beta/Schneeweiss, Beta/Sullivan) had lower AIC and higher R2 compared to risk ratio-based models (HR/Charlson, HR/Johnson). Regression coefficient-based CCS reclassified more number of people into the correct strata (NRI range, 9.02 10.04) compared to risk ratio-based CCS (NRI range, 8.14-8.22). CONCLUSION: Previously developed risk scores contained an error in their construction adding ratios instead of multiplying them. Furthermore, as demonstrated here, adding ratios fail to even work adequately from a practical standpoint. CCS derived using regression coefficients performed slightly better than in fitting the data compared to risk ratio-based scoring systems. Researchers should use a regression coefficient-based scoring system to develop a risk index, which is theoretically correct. PMID- 27181565 TI - Coronary Artery Bypass Grafting Versus Drug-Eluting Stents Implantation for Previous Myocardial Infarction. AB - Patients with previous myocardial infarction (MI) have a high risk of recurrence. Little is known about the effectiveness of coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) with drug-eluting stents (DES) in patients with a previous MI and left main or multivessel coronary artery disease (CAD). We compared long-term outcomes of these 2 strategies in 672 patients with previous MI and left main or multivessel CAD, who underwent CABG (n = 349) or PCI with DES (n = 323). A pooled database from the BEST, PRECOMBAT, and SYNTAX trials was analyzed, and the primary outcome was a composite of death from any causes, MI, or stroke. Baseline characteristics were similar between the 2 groups. The median follow-up duration was 59.8 months. The rate of the primary outcome was significantly lower with CABG than PCI (hazard ratio [HR] 0.59, 95% CI 0.42 to 0.82; p = 0.002). This difference was driven by a marked reduction in the rate of MI (HR 0.29, 95% CI 0.16 to 0.55, p <0.001). The benefit of CABG over PCI was consistent across all major subgroups. The individual risks of death from any causes or stroke were comparable between the 2 groups. Conversely, the rate of repeat revascularization was significantly lower with CABG than PCI (HR 0.34, 95% CI 0.22 to 0.51, p <0.001). In conclusion, in the patients with previous MI and left main or multivessel CAD, compared to PCI with DES, CABG significantly reduces the risk of death from any causes, MI, or stroke. PMID- 27181566 TI - Safety and Efficacy of Bivalirudin in Patients With Diabetes Mellitus Undergoing Percutaneous Coronary Intervention: From the REPLACE-2, ACUITY and HORIZONS-AMI Trials. AB - Optimal antithrombotic pharmacotherapy in patients affected by diabetes mellitus (DM) undergoing percutaneous coronary intervention is unclear. We sought to evaluate the safety and efficacy of bivalirudin compared with heparin plus a glycoprotein IIb/IIIa inhibitor (GPI) in patients with DM undergoing percutaneous coronary intervention. We pooled patient-level data from the Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events-2, Acute Catheterization and Urgent Intervention Triage strategy, and Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction trials. The primary efficacy end point was the incidence of major adverse cardiac events, defined as the composite of death, myocardial infarction, or unplanned revascularization at 30 days. The primary safety end point was the incidence of 30-day non-coronary artery bypass graft-related major bleeding. All-cause mortality was reported at 30 days and 1 year. Of the 14,737 patients included in the pooled database, 3,641 (24.7%) had DM. Patients with DM had higher rates of 30-day major bleeding and 30-day and 1-year all-cause mortality. There were no differences in 30-day major adverse cardiac events between bivalirudin versus heparin plus GPI in patients with DM (6.9% vs 7.8%; relative risk [RR] 0.89, 95% CI 0.71 to 1.12) or without DM (7.5% vs 6.7%; RR 1.11, 95% CI 0.97 to 1.27; pinteraction = 0.10). Bivalirudin treatment was associated with reduced risk of major bleeding in similar magnitude in patients with DM (4.3% vs 6.6% RR 0.68, 95% CI 0.51 to 0.89) or without DM (3.2% vs 6.1%; RR 0.51, 95% CI 0.43 to 0.61; pinteraction = 0.15). The hemorrhagic benefit of bivalirudin was noted for both access site- and non-access site-related bleeding. Overall, bivalirudin treatment was associated with a significant 1-year mortality benefit (2.7% vs 3.3%; RR 0.82, 95% CI 0.68 to 0.98; p = 0.03), which was consistent between patients with or without DM (pinteraction = 0.30). In conclusion, compared with heparin plus GPI, bivalirudin was associated with similar 30-day antithrombotic efficacy and better 30-day freedom from bleeding and 1-year mortality, irrespective of diabetic status. PMID- 27181573 TI - Postoperative Decrease in Platelet Counts Is Associated with Delayed Liver Function Recovery and Complications after Partial Hepatectomy. AB - Peripheral platelet counts decrease after partial hepatectomy; however, the implications of this phenomenon are unclear. We assessed if the observed decrease in platelet counts was associated with postoperative liver function and morbidity (complications grade <= II according to the Clavien-Dindo classification). We enrolled 216 consecutive patients who underwent partial hepatectomy for primary liver cancers, metastatic liver cancers, benign tumors, and donor hepatectomy. We classified patients as either low or high platelet percentage (postoperative platelet count/preoperative platelet count) using the optimal cutoff value calculated by a receiver operating characteristic (ROC) curve analysis, and analyzed risk factors for delayed liver functional recovery and morbidity after hepatectomy. Delayed liver function recovery and morbidity were significantly correlated with the lowest value of platelet percentage based on ROC analysis. Using a cutoff value of 60% acquired by ROC analysis, univariate and multivariate analysis determined that postoperative lowest platelet percentage <= 60% was identified as an independent risk factor of delayed liver function recovery (odds ratio (OR) 6.85; P < 0.01) and morbidity (OR, 4.90; P < 0.01). Furthermore, patients with the lowest platelet percentage <= 60% had decreased postoperative prothrombin time ratio and serum albumin level and increased serum bilirubin level when compared with patients with platelet percentage >= 61%. A greater than 40% decrease in platelet count after partial hepatectomy was an independent risk factor for delayed liver function recovery and postoperative morbidity. In conclusion, the decrease in platelet counts is an early marker to predict the liver function recovery and complications after hepatectomy. PMID- 27181567 TI - Ideal glycated hemoglobin cut-off points for screening diabetes and prediabetes in a Chinese population. AB - AIMS/INTRODUCTION: The aims of the present study were to evaluate the diagnostic value of fasting plasma glucose, 2-h postload plasma glucose and glycosylated hemoglobin (HbA1c) measurements in the screening of diabetes and prediabetes, and to determine the cut-off point of HbA1c in the diagnosis of diabetes and prediabetes in a Chinese population. MATERIALS AND METHODS: A total of 7,611 individuals aged 40 years or older, who did not have a prior history of diabetes, were randomly selected in the Changchun area. For each participant, a questionnaire was completed, and a physical examination and an oral glucose tolerance test were carried out. The values of fasting plasma glucose, 2-h postload plasma glucose and HbA1c were compared by area under the receiver operating characteristic curves. The Youden index was used to identify the optimal cut-off point of HbA1c in the diagnosis of diabetes and prediabetes. RESULTS: The prevalence of newly diagnosed diabetes and prediabetes was 12.71% and 29.39%, respectively. In participants with newly diagnosed diabetes, the area under the receiver operating characteristic curve was 0.8368 for fasting plasma glucose, 0.9330 for 2-h postload plasma glucose and 0.8064 for HbA1c; whereas for prediabetes, these values were 0.8022, 0.9288 and 0.6895, respectively. In addition, an HbA1c threshold of 6.3% showed the highest Youden index (0.4799) for detecting diabetes; furthermore, an HbA1c threshold of 5.8% showed the highest Youden index (0.2866) for detecting prediabetes. CONCLUSIONS: HbA1c >=6.3% (45 mmol/mol) and between 5.8% and 6.2% (40-44 mmol/mol) were the optimal cut-off values for the diagnosis of diabetes and prediabetes, respectively, in a Chinese population. PMID- 27181574 TI - A New Method and Mass Spectrometer Design for TOF-SIMS Parallel Imaging MS/MS. AB - We report a method for the unambiguous identification of molecules in biological and materials specimens at high practical lateral resolution using a new TOF-SIMS parallel imaging MS/MS spectrometer. The tandem mass spectrometry imaging reported here is based on the precise monoisotopic selection of precursor ions from a TOF-SIMS secondary ion stream followed by the parallel and synchronous collection of the product ion data. Thus, our new method enables simultaneous surface screening of a complex matrix chemistry with TOF-SIMS (MS(1)) imaging and targeted identification of matrix components with MS/MS (MS(2)) imaging. This approach takes optimal advantage of all ions produced from a multicomponent sample, compared to classical tandem mass spectrometric methods that discard all ions with the exception of specific ions of interest. We have applied this approach for molecular surface analysis and molecular identification on the nanometer scale. High abundance sensitivity is achieved at low primary ion dose density; therefore, one-of-a-kind samples may be relentlessly probed before ion beam-induced molecular damage is observed. PMID- 27181575 TI - Discovery of 1-((2R,4aR,6R,7R,7aR)-2-Isopropoxy-2-oxidodihydro-4H,6H spiro[furo[3,2-d][1,3,2]dioxaphosphinine-7,2'-oxetan]-6-yl)pyrimidine-2,4(1H,3H) dione (JNJ-54257099), a 3'-5'-Cyclic Phosphate Ester Prodrug of 2'-Deoxy-2' Spirooxetane Uridine Triphosphate Useful for HCV Inhibition. AB - JNJ-54257099 (9) is a novel cyclic phosphate ester derivative that belongs to the class of 2'-deoxy-2'-spirooxetane uridine nucleotide prodrugs which are known as inhibitors of the HCV NS5B RNA-dependent RNA polymerase (RdRp). In the Huh-7 HCV genotype (GT) 1b replicon-containing cell line 9 is devoid of any anti-HCV activity, an observation attributable to inefficient prodrug metabolism which was found to be CYP3A4-dependent. In contrast, in vitro incubation of 9 in primary human hepatocytes as well as pharmacokinetic evaluation thereof in different preclinical species reveals the formation of substantial levels of 2'-deoxy-2' spirooxetane uridine triphosphate (8), a potent inhibitor of the HCV NS5B polymerase. Overall, it was found that 9 displays a superior profile compared to its phosphoramidate prodrug analogues (e.g., 4) described previously. Of particular interest is the in vivo dose dependent reduction of HCV RNA observed in HCV infected (GT1a and GT3a) human hepatocyte chimeric mice after 7 days of oral administration of 9. PMID- 27181577 TI - Preparation and characterization of oxidized konjac glucomannan/carboxymethyl chitosan/graphene oxide hydrogel. AB - Polysaccharide hydrogels have been widely used as biomaterials in biomedical field. In this article, composite hydrogels were prepared through the Schiff-base reaction between the aldehyde of oxidized konjac glucomannan (OKGM) and the amino of carboxymethyl chitosan (CMCS). Meanwhile, different amount of graphene oxide (GO) was added as nano-additive. The hydrogels have been characterized by various methods including Fourier transform infrared spectroscopy (FT-IR) and Surface morphology (SEM). Through the observation of SEM, the hydrogels' scaffolds present a homogeneous interconnected pore structure after lyophilizing. In addition, the influence of different GO content on properties including gelation time, swelling ability, water evaporation rate and mechanical properties was investigated. The results indicate that the hydrogels have short gelation time, appropriate swelling ability and water evaporation rate. Especially, the compressive strength and modulus increase 144% and 296% respectively as the GO content increase from 0 to 5mg/ml. Moreover, MTT assay was applied to evaluate the biocompatibility of hydrogels. The result indicate that hydrogels with GO show better biocompatibility. Therefore, due to the appropriate water absorption capacity, the similar compressive modulus with soft tissue and excellent biocompatibility, the composite hydrogels have potential application in wound dressings. PMID- 27181576 TI - Efficacy and safety of ipragliflozin in Japanese patients with type 2 diabetes stratified by body mass index: A subgroup analysis of five randomized clinical trials. AB - AIMS/INTRODUCTION: The influence of overweight/obesity on the clinical efficacy and safety of sodium-glucose co-transporter 2 inhibitors is unclear. We carried out a pooled analysis to examine the impact of body mass index on the efficacy and safety of ipragliflozin. MATERIALS AND METHODS: Patient-level data were pooled for five Japanese double-blind trials (NCT00621868, NCT01057628, NCT01135433, NCT01225081 and NCT01242215) in which patients were randomized to ipragliflozin or a placebo as monotherapy, or in combination with metformin, pioglitazone or a sulfonylurea. Outcomes included the changes in hemoglobin A1c, fasting plasma glucose, bodyweight and treatment-emergent adverse events. Patients were divided into four body mass index categories. RESULTS: Hemoglobin A1c, fasting plasma glucose and bodyweight decreased significantly in the ipragliflozin group compared with the placebo group in all body mass index categories, and in the total cohort (all P < 0.001). Hemoglobin A1c did not improve in 11.2 and 69.2% of patients in the ipragliflozin and placebo groups, respectively. The change in hemoglobin A1c was weakly correlated with the change in bodyweight in all patients (r = 0.136, P = 0.002). Regarding laboratory variables, the placebo-subtracted difference tended to be greater in patients with higher body mass index for aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase and uric acid. The incidences of treatment-emergent adverse events were similar between the ipragliflozin and placebo groups in all patients combined and in the four body mass index categories. CONCLUSIONS: These results show that the efficacy and safety of ipragliflozin are not influenced by obesity/overweight in Japanese patients. PMID- 27181578 TI - Combining prebiotics with probiotic bacteria can enhance bacterial growth and secretion of bacteriocins. AB - There is a growing interest in supporting human health by using prebiotics, such as oligosaccharides, and beneficial bacteria, also called probiotics. Combining these two components we can develop synbiotics. In order to create successful combination of synbiotic it is very important to evaluate the influence of prebiotic oligosaccharides to probiotic bacteria and their behavior, such as growth and secretion of health related biomolecules, including bacteriocins. In this study seven type strains of probiotic bacteria (five Lactobacillus sp. and two Lactococcus sp.) and two Lactobacillus sp. strains, isolated from probiotic yoghurt, were cultivated with various commercially available and extracted oligosaccharides (OS). The aim of this study was to evaluate the influence of these OS on type and isolated bacterial strains growth and antibacterial activity. Obtained results suggest that combination of certain OS with probiotic strains may considerably improve their growth and/or antibacterial activity. We also determined the antibacterial activity spectrum of investigated strains with combination of OS against common food borne pathogens. Results of this work show that prebiotic OS can be useful for modulating probiotic bacteria growth, antibacterial activity and even specificity of this activity. PMID- 27181579 TI - Amoebiasis vaccine development: A snapshot on E. histolytica with emphasis on perspectives of Gal/GalNAc lectin. AB - Amoebiasis/amebiasis is a gastrointestinal infection caused by an enteric dwelling protozoan, Entamoeba histolytica. The disease is endemic in the developing world and is transmitted mainly via the faecal-oral route (e.g., in water or food) and may or may not be symptomatic. This disease of socio-economic importance worldwide involves parasite adherence and cytolysis of human cells followed by invasion that is mediated by galactose-binding (Gal/GalNAc) surface lectin. Disruption of the mucus layer leads to invasive intestinal and extraintestinal infection. Gal-lectin based vaccinations have conferred protection in various animal models against E. histolytica infections. Keeping in view the pivotal role of Gal/GalNAc lectin in amoebiasis vaccine development, its regulation, genomic view of the parasite involving gene conversion in lectin gene families, current knowledge about involvement of Gal/GalNAc lectin in adherence, pathogenicity, signalling, encystment, generating host immune response, and in turn protozoa escape strategies, and finally its role as effective vaccine candidate has been described. This review will help researchers to explore pathogenesis mechanism along with genomic studies and will also provide a framework for future amoebiasis vaccine development studies. PMID- 27181581 TI - Basophils go wild when mosquitoes bite CLL. PMID- 27181580 TI - Effects of supplementation with L. plantarum TN8 encapsulated in alginate chitosan in broiler chickens. AB - This study was undertaken to investigate the effects of supplementation of probiotic strain Lactobacillus plantarum TN8 encapsulated in sodium alginate chitosan or a commercial blend of essential oils on total cholesterol, High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL) and growth performance of broiler chickens. The results showed that the broiler chickens supplemented with encapsulated L. plantarum TN8 or essential oil has a higher growth than the control group. After 35days, the weight means were 1860 and 1880g respectively in dietary supplementation with probiotic or essential oil, while they are 1800g in the control group. The evolution of the feed consumption and feed conversion per week showed that the supplementation of encapsulated TN8 strain or essential oil in broiler chickens food has a positive influence on their appetite. Similarly, supplementation of the feed with this encapsulated strain significantly reduced the rate of cholesterol (HDL and LDL) as well as the contents of triglycerides in broiler chickens. Through our study, it appears that the use of the probiotic supplementation or essential oil to broilers were found to be better than the control group of chickens, resulting in a significant economic impact and promoting effect on health. PMID- 27181582 TI - Novel mechanism for counter-regulatory responses to hypoglycemia. AB - In the central nervous system, especially in the hypothalamus, the energy status in the body is assessed by glucose-sensing neurons since glucose is the major fuel in the central nervous system. Glucose sensing mechanisms also have a significant role in prevention of hypoglycemic bouts. In a recent report, Fan and colleagues proved a novel type of glucose-exited neurons which detect hypoglycemia through decreasing glucose entry via SGLT1. PMID- 27181583 TI - Genome engineering in ophthalmology: Application of CRISPR/Cas to the treatment of eye disease. AB - The Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) and CRISPR associated protein (Cas) system has enabled an accurate and efficient means to edit the human genome. Rapid advances in this technology could results in imminent clinical application, and with favourable anatomical and immunological profiles, ophthalmic disease will be at the forefront of such work. There have been a number of breakthroughs improving the specificity and efficacy of CRISPR/Cas-mediated genome editing. Similarly, better methods to identify off target cleavage sites have also been developed. With the impending clinical utility of CRISPR/Cas technology, complex ethical issues related to the regulation and management of the precise applications of human gene editing must be considered. This review discusses the current progress and recent breakthroughs in CRISPR/Cas-based gene engineering, and outlines some of the technical issues that must be addressed before gene correction, be it in vivo or in vitro, is integrated into ophthalmic care. We outline a clinical pipeline for CRISPR-based treatments of inherited eye diseases and provide an overview of the important ethical implications of gene editing and how these may influence the future of this technology. PMID- 27181585 TI - In vitro characterization of Leishmania (Viannia) braziliensis isolates from patients with different responses to Glucantime((r)) treatment from Northwest Parana, Brazil. AB - Leishmaniasis is a group of diseases that presents various clinical manifestations. Many studies have shown that the parasite plays an important role in the clinical manifestations and prognosis of this disease. The cutaneous and mucosal forms of American tegumentary leishmaniasis (ATL) are associated with Leishmania (Viannia) braziliensis, which exhibits intraspecific genetic polymorphisms and various clinical manifestations. The present study focused on four different L. braziliensis strains that were isolated from patients with distinct Glucantime((r)) treatment responses. The isolates were described based on their molecular, biological, and infective characteristics. Growth patterns in culture medium and different grow phases were analyzed, MID-Logarithimic (Mid LOG), Logarithimic (LOG) and Stationary (STAT) phases. Complement resistance was evaluated using guinea pig serum. Infection to murine peritoneal macrophages, cytokine and nitric oxide were analyzed. Ultrastructural features were determined by transmission electron microscopy, and molecular characteristics were determined based on random amplified polymorphic DNA (RAPD). All of the L. braziliensis isolates showed typical growth and similar complement sensitivity patterns. Markedly lower infectivity indexes were observed for all strains in the LOG phase, with different cytokine profiles. The ultrastructure analysis revealed distinct differences between the MID-LOG, LOG, and STAT phases. The RAPD results showed a divergence between the isolates of the L. braziliensis. The in vitro characterization of L. braziliensis isolates from humans with different treatment responses using various parameters enabled us to observe differences among the isolates. Molecular and in vivo characterizations are currently under study to improve understanding of the parasite-host interaction that can imply in the clinical manifestation differences. PMID- 27181587 TI - The effects of prism adaptation on daily life activities in patients with visuospatial neglect: a systematic review. AB - Studies that have investigated prism adaptation (PA) effects on symptoms of visuospatial neglect have primarily used neuropsychological tests as outcome measures. An important question that remains to be answered is whether PA effects translate into improvements in patients' daily life activities. In the present review, we examined systematically the evidence for the effect of PA treatment on daily life activities in patients with neglect. Two authors independently assessed the methodological quality of 25 intervention and 1 follow-up studies using validated scales. PA effects were evaluated for reading/writing, activities of daily living (ADL) direct tests, ADL questionnaires, and navigation tests. Studies were evaluated as being of excellent (n = 1), good (n = 12), fair (n = 10), or poor (n = 3) quality. Among the 26 articles, a total of 32 measurements showed significant PA effects (one measurement from a study of excellent quality, 17 from studies of good quality, 10 from studies of fair quality, four from studies of poor quality), whereas non-significant effects were found in 15 measurements (two from a study of excellent quality, three from studies of good quality, eight from studies of fair quality, two from studies of poor quality). There is some evidence suggesting that PA can improve daily functioning, particularly as measured by reading/writing and ADL direct tests. The impact of several variables on PA effects should be investigated further including sample heterogeneity and time since injury. PMID- 27181586 TI - Berberine activates peroxisome proliferator-activated receptor gamma to increase atherosclerotic plaque stability in Apoe-/- mice with hyperhomocysteinemia. AB - AIMS/INTRODUCTION: An elevated level of plasma homocysteine has long been suspected as a metabolic risk factor for the development of atherosclerotic vascular diseases in diabetes. Berberine (BBR) has several preventive effects on cardiovascular diseases. The effects of BBR on atherosclerotic plaque stability increased by homocysteine thiolactone (HTL) remain unknown. MATERIALS AND METHODS: The model of atherosclerotic vulnerable plaque was induced by placing a collar around the carotid artery in Apoe-/- mice. Endothelium-dependent relaxation was assayed by organ chamber. RESULTS: Homocysteine thiolactone (50 mg/kg/day, 8 weeks) reduced the atherosclerotic plaque stability in the carotid artery of Apoe-/- mice, which was reversed by BBR administration (1.0 g/kg/day). In vivo and ex vivo experiments showed that HTL dramatically reduced acetylcholine-induced endothelium-dependent relaxation and superoxide dismutase activity, and increased malondialdehyde content, which were inhibited by BBR. Importantly, all effects induced by BBR were abolished by GW9662, an antagonist of peroxisome proliferator-activated receptor-gamma. Incubation of cultured endothelial cells with HTL significantly reduced cell viabilities and enhanced production of reactive oxygen species. Pretreatment of cells with BBR dose dependently reversed HTL-induced detrimental effects, which were GW9662 reversible. CONCLUSIONS: Berberine increases atherosclerotic plaque stability in hyperhomocysteinemia mice, which is related to the activation of peroxisome proliferator-activated receptor-gamma and subsequent suppression of oxidative stress in endothelial cells. PMID- 27181584 TI - Potent neutralizing monoclonal antibodies against Ebola virus infection. AB - Ebola virus infections cause a deadly hemorrhagic disease for which no vaccines or therapeutics has received regulatory approval. Here we show isolation of three (Q206, Q314 and Q411) neutralizing monoclonal antibodies (mAbs) against the surface glycoprotein (GP) of Ebola virus identified in West Africa in 2014 through sequential immunization of Chinese rhesus macaques and antigen-specific single B cell sorting. These mAbs demonstrated potent neutralizing activities against both pseudo and live Ebola virus independent of complement. Biochemical, single particle EM, and mutagenesis analysis suggested Q206 and Q411 recognized novel epitopes in the head while Q314 targeted the glycan cap in the GP1 subunit. Q206 and Q411 appeared to influence GP binding to its receptor NPC1. Treatment with these mAbs provided partial but significant protection against disease in a mouse model of Ebola virus infection. These novel mAbs could serve as promising candidates for prophylactic and therapeutic interventions against Ebola virus infection. PMID- 27181588 TI - Reliability of the Suchey-Brooks method for a French contemporary population. AB - The Suchey-Brooks method is commonly used for pubic symphyseal aging in forensic cases. However, inter-population variability is a problem affected by several factors such as geographical location and secular trends. The aim of our study was to test the reliability of the Suchey-Brooks method on a virtual sample of contemporary French males. We carried out a retrospective study of 680 pubic symphysis from adult males undergoing clinical Multislice Computed Tomography in two hospitals between January 2013 and July 2014 (Toulouse and Tours, France). The reliability of the Suchey-Brooks method was tested by the calculation of inaccuracy and bias between real and estimated ages, and the mean age for each stage and the mean stage for each 10-years age interval were compared. The degree of inaccuracy and bias increased with age and inaccuracy exceeded 20 years for individuals over 65 years of age. The results are consistent with an overestimation of the real age for stages I and II and an underestimation of the real age for stages IV, V and VI. Furthermore, the mean stages of the reference sample were significantly lower for the 14-25 age group and significantly higher for individuals over 35 years old. Age estimation is potentially limited by differential inter-population error rates between geographical locations. Furthermore, the effects of secular trends are also supported by research in European countries showing a reduction in the age of attainment of indicators of biological maturity during the past few decades. The results suggest that the Suchey-Brooks method should be used with caution in France. Our study supports previous findings and in the future, the Suchey-Brooks method could benefit from re-evaluation of the aging standards by the establishment of new virtual reference samples. PMID- 27181589 TI - A guideline for the validation of likelihood ratio methods used for forensic evidence evaluation. AB - This Guideline proposes a protocol for the validation of forensic evaluation methods at the source level, using the Likelihood Ratio framework as defined within the Bayes' inference model. In the context of the inference of identity of source, the Likelihood Ratio is used to evaluate the strength of the evidence for a trace specimen, e.g. a fingermark, and a reference specimen, e.g. a fingerprint, to originate from common or different sources. Some theoretical aspects of probabilities necessary for this Guideline were discussed prior to its elaboration, which started after a workshop of forensic researchers and practitioners involved in this topic. In the workshop, the following questions were addressed: "which aspects of a forensic evaluation scenario need to be validated?", "what is the role of the LR as part of a decision process?" and "how to deal with uncertainty in the LR calculation?". The questions: "what to validate?" focuses on the validation methods and criteria and "how to validate?" deals with the implementation of the validation protocol. Answers to these questions were deemed necessary with several objectives. First, concepts typical for validation standards [1], such as performance characteristics, performance metrics and validation criteria, will be adapted or applied by analogy to the LR framework. Second, a validation strategy will be defined. Third, validation methods will be described. Finally, a validation protocol and an example of validation report will be proposed, which can be applied to the forensic fields developing and validating LR methods for the evaluation of the strength of evidence at source level under the following propositions. PMID- 27181590 TI - Neurodegeneration Alters Metabolic Profile and Sirt 1 Signaling in High-Fat Induced Obese Mice. AB - Different factors may contribute to the development of neurodegenerative diseases. Among them, metabolic syndrome (MS), which has reached epidemic proportions, has emerged as a potential element that may be involved in neurodegeneration. Furthermore, studies have shown the importance of the sirtuin family in neuronal survival and MS, which opens the possibility of new pharmacological targets. This study investigates the influence of sirtuin metabolic pathways by examining the functional capacities of glucose-induced obesity in an excitotoxic state induced by a quinolinic acid (QA) animal model. Mice were divided into two groups that received different diets for 8 weeks: one group received a regular diet, and the other group received a high-fat diet (HF) to induce MS. The animals were submitted to a stereotaxic surgery and subdivided into four groups: Standard (ST), Standard-QA (ST-QA), HF and HF-QA. The QA groups were given a 250 nL quinolinic acid injection in the right striatum and PBS was injected in the other groups. Obese mice presented with a weight gain of 40 % more than the ST group beyond acquiring an insulin resistance. QA induced motor impairment and neurodegeneration in both ST-QA and HF-QA, although no difference was observed between these groups. The HF-QA group showed a reduction in adiposity when compared with the groups that received PBS. Therefore, the HF-QA group demonstrated a commitment-dependent metabolic pathway. The results suggest that an obesogenic diet does not aggravate the neurodegeneration induced by QA. However, the excitotoxicity induced by QA promotes a sirtuin pathway impairment that contributes to metabolic changes. PMID- 27181591 TI - Thrombin Enhanced Matrix Metalloproteinase-9 Expression and Migration of SK-N-SH Cells via PAR-1, c-Src, PYK2, EGFR, Erk1/2 and AP-1. AB - Neuroinflammation is a hallmark of neurodegenerative disorders in the central nerve system (CNS). Thrombin has been known as one of the factors in pathological processes including migration, blood-brain barrier breakdown, brain edema formation, neuroinflammation, and neuronal death. Thrombin has been shown to be a regulator of matrix metalloproteinase (MMPs) expression leading to cell migration. Among MMPs, the elevated expression of MMP-9 has been observed in patients with brain diseases, which may contribute to the pathology of neuroinflammatory and neurodegenerative diseases. However, the mechanisms underlying thrombin-induced MMP-9 expression in SK-N-SH cells were not completely understood. Here, we used gelatin zymography, Western blot, real-time PCR, promoter activity assay, and cell migration assay to demonstrate that thrombin induced the expression of pro-form MMP-9 protein and messenger RNA (mRNA), and promoter activity in SK-N-SH cells, which were attenuated by pretreatment with the pharmacological inhibitor of protease-activated receptor-1 (PAR-1, SCH79797), Gi-coupled receptor (GPA2), c-Src (PP1), Pyk2 (PF431396), EGFR (AG1478), PI3K (LY294002), Akt (SH-5), MEK1/2 (U0126), or AP-1 (TanshinoneIIA) and transfection with small interfering RNA (siRNA) of PAR-1, Gi, c-Src, Pyk2, EGFR, Akt, p44, p42, or c-Jun. Moreover, thrombin-stimulated c-Src, Pyk2, EGFR, Akt, p42/p44 MAPK, or c-Jun phosphorylation was attenuated by their respective inhibitor of PP1, PF431396, AG1478, SH-5, U0126, or TanshinoneIIA. Finally, pretreatment with these inhibitors also blocked thrombin-induced SK-N-SH cell migration. Our results concluded that thrombin binding to PAR-1 receptor activated Gi-protein/c Src/Pyk2/EGFR/PI3K/Akt/p42/p44 MAPK cascade, which in turn elicited AP-1 activation and ultimately evoked MMP-9 expression and cell migration in SK-N-SH cells. PMID- 27181592 TI - JNK Activation Contributes to Oxidative Stress-Induced Parthanatos in Glioma Cells via Increase of Intracellular ROS Production. AB - Parthanatos is a form of PARP-1-dependent programmed cell death. The induction of parthanatos is emerging as a new strategy to kill gliomas which are the most common type of primary malignant brain tumor. Oxidative stress is thought to be a critical factor triggering parthanatos, but its underlying mechanism is poorly understood. In this study, we used glioma cell lines and H2O2 to investigate the role of JNK in glioma cell parthanatos induced by oxidative stress. We found that exposure to H2O2 not only induced intracellular accumulation of ROS but also resulted in glioma cell death in a concentration- and incubation time-dependent manner, which was accompanied with cytoplasmic formation of PAR polymer, expressional upregulation of PARP-1, mitochondrial depolarization, and AIF translocation to nucleus. Pharmacological inhibition of PARP-1 with 3AB or genetic knockdown of its level with siRNA rescued glioma cell death, as well as suppressed cytoplasmic accumulation of PAR polymer and nuclear translocation of AIF, which were consistent with the definition of parthanatos. Moreover, the phosphorylated level of JNK increased markedly with the extension of H2O2 exposure time. Either attenuation of intracellular ROS with antioxidant NAC or inhibition of JNK phosphorylation with SP600125 or JNK siRNA could significantly prevent H2O2-induced parthanatos in glioma cells. Additionally, inhibition of JNK with SP600125 alleviated intracellular accumulation of ROS and attenuated mitochondrial generation of superoxide. Thus, we demonstrated that JNK activation contributes to glioma cell parthanatos caused by oxidative stress via increase of intracellular ROS generation. PMID- 27181593 TI - CYP2C93 variant is associated with antidiabetes efficacy of gliclazide in Chinese type 2 diabetes patients. AB - AIMS/INTRODUCTION: The objective of the present study was to investigate the effects of CYP2C9*3 polymorphisms on the therapeutic response to gliclazide in type 2 diabetes patients. MATERIALS AND METHODS: A total of 746 incident type 2 diabetes patients were included in this study. After enrolment, patients went on 4-week gliclazide monotherapy. Fasting plasma glucose was measured before and after treatment. Hypoglycemia episodes and lifestyle information were collected by weekly follow up. Genotyping of rs1057910 was carried out using the single base primer extension method. The t-test, analysis of variance and chisquare-test were used to evaluate the effects of rs1057910 alleles on the therapeutic response to gliclazide. RESULTS: After the therapy, fasting plasma glucose decreased significantly from 11.2 +/- 2.7 mmol/L to 8.0 +/- 2.2 mmol/L (P < 0.001). Patients with AC/CC genotypes of rs1057910 had a greater reduction of fasting plasma glucose (3.6 vs 3.0 mmol/L, P < 0.001; 31.4 vs 24.5%, P < 0.001) and a higher rate of treatment success (54.7 vs 37.5%, P < 0.001; 51.4 vs 32.3%, P < 0.001; 71.6 vs 48.3%, P < 0.001 for criterion 1, 2 and 3, respectively). CONCLUSIONS: The present study showed that the polymorphism at rs1057910 significantly affected the therapeutic response of gliclazide in type 2 diabetes mellitus patients. The risk allele is associated with a greater decrease of fasting blood glucose and a higher rate of treatment success with gliclazide monotherapy. PMID- 27181594 TI - Inflammatory insults and mental health consequences: does timing matter when it comes to depression? AB - It has become widely accepted that the immune system, and specifically increased levels of inflammation, play a role in the development of depression. However, not everyone with increased inflammation develops depression, and as with all other diseases, there are risk factors that may contribute to an increased vulnerability in certain individuals. One such risk factor could be the timing of an inflammatory exposure. Here, using a combination of PubMed, EMBASE, Ovid Medline and PsycINFO, we systematically reviewed whether exposure to medically related inflammation in utero, in childhood, and in adolescence, increases the risk for depression in adulthood. Moreover, we tried to determine whether there was sufficient evidence to identify a particular time point during the developmental trajectory in which an immune insult could be more damaging. While animal research shows that early life exposure to inflammation increases susceptibility to anxiety- and depressive-like behaviour, human studies surprisingly find little evidence to support the notion that medically related inflammation in utero and in adolescence contributes to an increased risk of developing depression in later life. However, we did find an association between childhood inflammation and later life depression, with most studies reporting a significantly increased risk of depression in adults who were exposed to inflammation as children. More robust clinical research, measuring direct markers of inflammation throughout the life course, is greatly needed to expand on, and definitively address, the important research questions raised in this review. PMID- 27181597 TI - Regulatory policy for research and development of vaccines for public health emergencies. PMID- 27181596 TI - Deficiency of dietary niacin impaired gill immunity and antioxidant capacity, and changes its tight junction proteins via regulating NF-kappaB, TOR, Nrf2 and MLCK signaling pathways in young grass carp (Ctenopharyngodon idella). AB - To investigate the effects of dietary niacin on gill immunity, tight junction proteins, antioxidant system and related signaling molecules mRNA expression, young grass carp (Ctenopharyngodon idella) were fed six diets containing graded levels of niacin (3.95-55.01 mg/kg diet) for 8 weeks. The study indicated that niacin deficiency decreased lysozyme and acid phosphatase activities, and complement 3 content, and caused oxidative damage that might be partly due to the decreased copper, zinc superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase and glutathione-S-transferase activities and reduced glutathione content in fish gills (P < 0.05). Moreover, the relative mRNA levels of antimicrobial peptides (liver expressed antimicrobial peptide 2 and Hepcidin), anti-inflammatory cytokines (interleukin 10 and transforming growth factor beta1), tight junction proteins (Occludin, zonula occludens 1, Claudin-15 and 3), signaling molecules (inhibitor of kappaBalpha (IkappaBalpha), target of rapamycin (TOR), ribosomal protein S6 kinase 1 (S6K1) and NF-E2-related factor 2 (Nrf2)) and antioxidant enzymes were significantly decreased (P < 0.05) in niacin deficient diet group. Conversely, the mRNA levels of pro-inflammatory cytokines (tumor necrosis factor alpha, interleukin 8, interferon gamma2, and interleukin 1beta), signaling molecules (nuclear factor kappa B p65, IkappaB kinase alpha, IkappaB kinase beta, IkappaB kinase gamma, Kelch-like-ECH-associated protein 1b, myosin light chain kinase and p38 mitogen-activated protein kinase (p38 MAPK) were significantly increased (P < 0.05) in fish gills fed niacin-deficient diet. Interestingly, the varying niacin levels of 3.95-55.01 mg/kg diet had no effect on the mRNA level of Kelch-like-ECH-associated protein 1a, Claudin-c and -12 in fish gills (P > 0.05). In conclusion, niacin deficiency decreased gill immunity, impaired gill antioxidant system, as well as regulated mRNA expression of gill tight junction proteins and related signaling molecules of fish. PMID- 27181595 TI - Streptococcal pyrogenic exotoxin B inhibits apoptotic cell clearance by macrophages through protein S cleavage. AB - Clearance of apoptotic cells by macrophages plays an important role in maintaining tissue homeostasis. Previous study indicated that streptococcal pyrogenic exotoxin B (SPE B) reduces phagocytic activity in group A streptococcus (GAS) infection. Here, we demonstrate that SPE B causes an inhibitory effect on protein S-mediated phagocytosis. In the presence of SPE B, serum- and purified protein S-mediated phagocytosis of apoptotic cells were significantly inhibited. The binding abilities of protein S to apoptotic cells were decreased by treatment with SPE B. Bacterial culture supernatants from GAS NZ131 strain also caused a reduction of protein S binding to apoptotic cells, but speB mutant strain did not. SPE B directly cleaved protein S in vitro and in vivo, whereas a lower level of cleavage occurred in mice infected with a speB isogenic mutant strain. SPE B mediated initial cleavage of protein S caused a disruption of phagocytosis, and also resulted in a loss of binding ability of protein S-associated C4b-binding protein to apoptotic cells. Taken together, these results suggest a novel pathogenic role of SPE B that initiates protein S degradation followed by the inhibition of apoptotic cell clearance by macrophages. PMID- 27181598 TI - Effect of Soy Sauce on Serum Uric Acid Levels in Hyperuricemic Rats and Identification of Flazin as a Potent Xanthine Oxidase Inhibitor. AB - This is the first report on the ability of soy sauce to effectively reduce the serum uric acid levels and xanthine oxidase (XOD) activities of hyperuricemic rats. Soy sauce was partitioned sequentially into ethyl acetate and water fractions. The ethyl acetate fraction with strong XOD inhibition effect was purified further. On the basis of xanthine oxidase inhibitory (XOI) activity guided purification, nine compounds including 3,4-dihydroxy ethyl cinnamate, diisobutyl terephthalate, harman, daidzein, flazin, catechol, thymine, genistein, and uracil were obtained. It was the first time that 3,4-dihydroxy ethyl cinnamate and diisobutyl terephthalate had been identified from soy sauce. Flazin with hydroxymethyl furan ketone group at C-1 and carboxyl at C-3 exhibited the strongest XOI activity (IC50 = 0.51 +/- 0.05 mM). According to fluorescence quenching and molecular docking experiments, flazin could enter into the catalytic center of XOD to interact with Lys1045, Gln1194, and Arg912 mainly by hydrophobic forces and hydrogen bonds. Flazin, catechol, and genistein not only were potent XOD inhibitors but also held certain antioxidant activities. According to ADME (absorption, distribution, metabolism, and excretion) simulation in silico, flazin had good oral bioavailability in vivo. PMID- 27181601 TI - Monomolecular adsorption on nanoparticles with repulsive interactions: a Monte Carlo study. AB - In the present work, we study the adsorption of different monomolecular species on nanoparticles with different sizes and geometries using a grand canonical Monte Carlo method. These species are characterized by repulsive lateral interactions between themselves, as takes place in the case of the adsorption of partially charged atoms or molecules. Nanosize effects are analyzed in terms of adsorption on edge and facet sites. The energy minimization in these systems comes out as a complex conjugation of the repulsive lateral interactions between the adsorbates and the attractive interactions of the adsorbates with the nanoparticle. The phenomenon is analyzed as a function of the occurrence of different ordered structures being formed on the surface of the nanoparticle. We find that layers with different structures may coexist on different facets of the nanoparticle. Finally, a discussion of deposition on flat surfaces and in finite systems is given. PMID- 27181599 TI - Proposed cut-off values of the waist circumference for metabolic syndrome based on visceral fat volume in a Japanese population. AB - AIM/INTRODUCTION: Waist circumference (WC) is the most important parameter for diagnosis of metabolic syndrome. The present study was carried out to obtain optimal WC cut-off values for diagnosis of metabolic syndrome in a Japanese population based on the measurement of total intra-abdominal visceral fat volume (VFV), which could be expected to reflect visceral obesity more precisely than visceral fat area. MATERIALS AND METHODS: A total of 405 Japanese persons undergoing health screening were investigated. visceral fat volume was calculated from the data in 700-800 computed tomography slices from the top of the liver to the floor of the pelvic cavity. Then, receiver operating characteristic analysis was used to determine the cut-off value of the VFV/height ratio. Subsequently, the corresponding WC value was obtained by linear regression analysis. RESULTS: The cut-off value of the VFV/height ratio was 2,317 cm(3) /m in men and 1,425 cm(3) /m in women. The sensitivity and specificity of the ratio were 52.9 and 86.4% in men vs 63.4 and 82.2% in women, respectively. The corresponding cut-off value of WC was 86.0 cm in men and 80.9 cm in women. CONCLUSIONS: The proposed cut-off values of WC for metabolic syndrome are 85 cm in Japanese men and 80 cm in Japanese women. PMID- 27181600 TI - Food and Waterborne Disease in the Greater New York City Area Following Hurricane Sandy in 2012. AB - OBJECTIVE: We aimed to evaluate residence in evacuation areas (storm areas) as a risk factor for food and waterborne disease (FWBD) associated with Hurricane Sandy flooding. METHODS: We captured 9601 incident outpatient and inpatient FWBD hospital discharge diagnoses for residents of the greater New York City area. We used Poisson or negative binomial regression models to compare the covariate adjusted risk for a FWBD diagnosis, pre-Sandy (10/28-11/09, 2001-2011) vs. post Sandy (10/28-11/09, 2012), for residents of "storm" and "non-storm" areas. RESULTS: Outpatient FWBD risk was lower for storm area residents after Hurricane Sandy (risk ratio [RR]=0.58, 95% confidence interval [CI]: 0.46-0.74), and varied by age, sex, and county. However, storm area residents 65 years of age or older experienced higher risk after Hurricane Sandy (RR=2.16, 95% CI: 1.11-4.19), albeit based on few cases. Inpatient FWBD risk was lower for non-storm area residents after Hurricane Sandy (RR=0.79, 95% CI: 0.66-0.95), and varied by age, race, and county, although there was no significant change for storm area residents (RR=0.86, 95% CI: 0.69-1.08). Those >=65 years of age were also at lower risk for inpatient FWBD diagnosis, yet the effect was weaker for storm area (RR=0.89, 95% CI: 0.67-1.18) than for non-storm area residents (RR=0.68, 95% CI: 0.52-0.89). CONCLUSIONS: Hurricane preparation, mitigation, and response activities in the greater New York City area may have led to "protective" effects for FWBD. (Disaster Med Public Health Preparedness. 2016;10:503-511). PMID- 27181602 TI - Optimal cut-off levels of obesity indices by different definitions of metabolic syndrome in a southeast rural Chinese population. AB - AIMS/INTRODUCTION: The aim of the present study was to compare the cut-off values and prediction effect of different obesity indices by different definitions of metabolic syndrome (MetS) in Zhejiang Province of China. MATERIALS AND METHODS: We carried out a cross-sectional survey of 10,100 individuals (age 40 years and older) in Jiashan, Zhejiang Province. Receiver operating characteristic analysis was used to examine discrimination and find optimal cut off values of waist circumference (WC), body mass index (BMI), waist-to-hip ratio (WHR) and waist-to height ratio (WHtR) to predict two or more non-adipose components of MetS by The National Cholesterol Education Program Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III) definition modified by the Asia-Pacific region criteria, International Diabetes Federation definition for the Chinese population and Chinese Diabetes Society definitions of MetS. RESULTS: The age-standardized prevalence of MetS was 23.78% vs 28.76% vs 19.37% by The National Cholesterol Education Program Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III), International Diabetes Federation and Chinese Diabetes Society definitions, respectively. Cut-off values of BMI were approximately 24 kg/m(2) both in men and women by three definitions; the average cut-off values of WC, WHR and WHtR were 83 cm in men vs 81 cm in women, 0.89 in men vs 0.86 in women and 0.50 in men vs 0.51 in women, respectively. The area under receiver operating characteristic curve of BMI was larger than WC both in men and women (P < 0.05); in women, the area under receiver operating characteristic curve of WHtR was larger than WC, and WHR was smaller. CONCLUSIONS: MetS is prevalent in Zhejiang Province of China, especially in the female population. BMI and WHtR might be more useful than WC and WHR for predicting two or more non-adipose components of MetS. PMID- 27181603 TI - Speech motor learning changes the neural response to both auditory and somatosensory signals. AB - In the present paper, we present evidence for the idea that speech motor learning is accompanied by changes to the neural coding of both auditory and somatosensory stimuli. Participants in our experiments undergo adaptation to altered auditory feedback, an experimental model of speech motor learning which like visuo-motor adaptation in limb movement, requires that participants change their speech movements and associated somatosensory inputs to correct for systematic real-time changes to auditory feedback. We measure the sensory effects of adaptation by examining changes to auditory and somatosensory event-related responses. We find that adaptation results in progressive changes to speech acoustical outputs that serve to correct for the perturbation. We also observe changes in both auditory and somatosensory event-related responses that are correlated with the magnitude of adaptation. These results indicate that sensory change occurs in conjunction with the processes involved in speech motor adaptation. PMID- 27181605 TI - Morphology controlled synthesis of platinum nanoparticles performed on the surface of graphene oxide using a gas-liquid interfacial reaction and its application for high-performance electrochemical sensing. AB - In this paper, we report a novel morphology-controlled synthetic method. Platinum (Pt) nanoparticles with three kinds of morphology (aggregation-like, cube-like and globular) were grown on the surface of graphene oxide (GO) using a simple gas liquid interfacial reaction and Pt/GO nanocomposites were obtained successfully. According to the experimental results, the morphology of the Pt nanoparticles can be controlled by adjusting the reaction temperature with the protection of chitosan. The obtained Pt/GO nanocomposites were characterized using transmission electron microscopy (TEM), X-ray diffraction (XRD) and fourier transform infrared spectroscopy (FTIR). Then the Pt/GO nanocomposites with the three kinds of morphology were all used to fabricate electrochemical sensors. The electrochemical experimental results indicated that compared with various reported electrochemical sensors, the Pt/GO modified sensors in this work exhibit a low detection limit, high sensitivity and an extra wide linear range for the detection of nitrite. In addition, the synthesis of Pt particles based on a gas liquid interfacial reaction provides a new platform for the controllable synthesis of nanomaterials. PMID- 27181604 TI - Twenty year fitness trends in young adults and incidence of prediabetes and diabetes: the CARDIA study. AB - AIMS/HYPOTHESIS: The prospective association between cardiorespiratory fitness (CRF) measured in young adulthood and middle age on development of prediabetes, defined as impaired fasting glucose and/or impaired glucose tolerance, or diabetes by middle age remains unknown. We hypothesised that higher fitness levels would be associated with reduced risk for developing incident prediabetes/diabetes by middle age. METHODS: Participants were from the Coronary Artery Risk Development in Young Adults (CARDIA) study who were free from prediabetes/diabetes at baseline (year 0 [Y0]: 1985-1986). CRF was quantified by treadmill duration (converted to metabolic equivalents [METs]) at Y0, Y7 and Y20 and prediabetes/diabetes status was assessed at Y0, Y7, Y10, Y15, Y20 and Y25. We use an extended Cox model with CRF as the primary time-varying exposure. BMI was included as a time-varying covariate. The outcome was development of either prediabetes or diabetes after Y0. Model 1 included age, race, sex, field centre, CRF and BMI. Model 2 additionally included baseline (Y0) smoking, energy intake, alcohol intake, education, systolic BP, BP medication use and lipid profile. RESULTS: Higher fitness was associated with lower risk for developing incident prediabetes/diabetes (difference of 1 MET: HR 0.99898 [95% CI 0.99861, 0.99940], p < 0.01), which persisted (difference of 1 MET: HR 0.99872 [95% CI 0.99840, 0.99904], p < 0.01] when adjusting for covariates. CONCLUSIONS/INTERPRETATION: Examining participants who had fitness measured from young adulthood to middle age, we found that fitness was associated with lower risk for developing prediabetes/diabetes, even when adjusting for BMI over this time period. These findings emphasise the importance of fitness in reducing the health burden of prediabetes and diabetes. PMID- 27181608 TI - Site-Selective N-Dealkylation of 1,2,3-Triazolium Salts: A Metal-Free Route to 1,5-Substituted 1,2,3-Triazoles and Related Bistriazoles. AB - N3-Alkylation of 1-(pivaloyloxymethyl)-1,2,3-triazoles with alkyl triflates carrying latent "click" functionality, followed by a nucleophile-promoted N1 dealkylation of the resulting strongly electrophilic intermediate triazolium salts, provides an efficient route to 1,5-disubstituted 1,2,3-triazoles. The azide and alkyne groups incorporated by N-alkylation can be submitted to further copper-catalyzed azide-alkyne and Huisgen cycloadditions to provide bis(1,2,3 triazoles) with unprecedented 1,5/1,4 substitution patterns. PMID- 27181607 TI - Effect of DSP4 and desipramine in the sensorial and affective component of neuropathic pain in rats. AB - Previous findings suggest that neuropathic pain induces characteristic changes in the noradrenergic system that may modify the sensorial and affective dimensions of pain. We raise the hypothesis that different drugs that manipulate the noradrenergic system can modify specific domains of pain. In the chronic constriction injury (CCI) model of neuropathic pain, the sensorial (von Frey and acetone tests) and the affective (place escape/avoidance paradigm) domains of pain were evaluated in rats 1 and 2weeks after administering the noradrenergic neurotoxin [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride] (DSP4, 50mg/kg). In other animals, we evaluated the effect of enhancing noradrenergic tone in the 2weeks after injury by administering the antidepressant desipramine (10mg/kg/day, delivered by osmotic minipumps) during this period, a noradrenaline reuptake inhibitor. Moreover, the phosphorylation of the extracellular signal regulated kinases (p-ERK) in the anterior cingulate cortex (ACC) was also assessed. The ACC receives direct inputs from the main noradrenergic nucleus, the locus coeruleus, and ERK activation has been related with the expression of pain related negative affect. These studies revealed that DSP4 almost depleted noradrenergic axons in the ACC and halved noradrenergic neurons in the locus coeruleus along with a decrease in the affective dimension and an increased of p ERK in the ACC. However, it did not modify sensorial pain perception. By contrast, desipramine reduced pain hypersensitivity, while completely impeding the reduction of the affective pain dimension and without modifying the amount of p-ERK. Together results suggest that the noradrenergic system may regulate the sensorial and affective sphere of neuropathic pain independently. PMID- 27181609 TI - Synthesis of Cyclic Guanidines via Silver-Catalyzed Intramolecular Alkene Hydroamination Reactions of N-Allylguanidines. AB - The silver-catalyzed hydroamination of tosyl-protected N-allylguanidines is described. These reactions provide substituted cyclic guanidines in high yields. The reactions are amenable to the construction of quaternary stereocenters as well as both monocyclic and bicyclic guanidine products. PMID- 27181610 TI - Surface-Cross-Linked Micelles as Multifunctionalized Organic Nanoparticles for Controlled Release, Light Harvesting, and Catalysis. AB - Surfactant micelles are dynamic entities with a rapid exchange of monomers. By "clicking" tripropargylammonium-containing surfactants with diazide cross linkers, we obtained surface-cross-linked micelles (SCMs) that could be multifunctionalized for different applications. They triggered membrane fusion through tunable electrostatic interactions with lipid bilayers. Antenna chromophores could be installed on them to create artificial light-harvesting complexes with efficient energy migration among tens to hundreds of chromophores. When cleavable cross-linkers were used, the SCMs could break apart in response to redox or pH signals, ejecting entrapped contents quickly as a result of built-in electrostatic stress. They served as caged surfactants whose surface activity was turned on by environmental stimuli. They crossed cell membranes readily. Encapsulated fluorophores showed enhanced photophysical properties including improved quantum yields and greatly expanded Stokes shifts. Catalytic groups could be installed on the surface or in the interior, covalently attached or physically entrapped. As enzyme mimics, the SCMs enabled rational engineering of the microenvironment around the catalysts to afford activity and selectivity not possible with conventional catalysts. PMID- 27181611 TI - Magnetic effervescent tablet-assisted ionic liquid dispersive liquid-liquid microextraction of selenium for speciation in foods and beverages. AB - A novel, simple and rapid method based on magnetic effervescent tablet-assisted ionic liquid dispersive liquid-liquid microextraction (MEA-IL-DLLME) followed by graphite furnace atomic absorption spectrometry (GFAAS) determination was established for the speciation of selenium in various food and beverage samples. In the procedure, a special magnetic effervescent tablet containing CO2 sources (sodium carbonate and sodium dihydrogenphosphate), ionic liquids and Fe3O4 magnetic nanoparticles (MNPs) was used to combine extractant dispersion and magnetic recovery procedures into a single step. The parameters influencing the microextraction efficiency, such as pH of the sample solution, volume of ionic liquid, amount of MNPs, concentration of the chelating agent, salt effect and matrix effect were investigated and optimised. Under the optimised conditions, the limits of detection (LODs) for Se(IV) were 0.021 MUg l(-)(1) and the linear dynamic range was 0.05-5.0 MUg l(-)(1). The relative standard deviation for seven replicate measurements of 1.0 MUg l(-)(1) of Se(IV) was 2.9%. The accuracy of the developed method was evaluated by analysis of the standard reference materials (GBW10016 tea, GBW10017 milk powder, GBW10043 Liaoning rice, GBW10046 Henan wheat, GBW10048 celery). The proposed method was successfully applied to food and beverage samples including black tea, milk powder, mushroom, soybean, bamboo shoots, energy drink, bottled water, carbonated drink and mineral water for the speciation of Se(IV) and Se(VI) with satisfactory relative recoveries (92.0 108.1%). PMID- 27181613 TI - Conditioned stress prevents cue-primed cocaine reinstatement only in stress responsive rats. AB - Neurobiological mechanisms underlying comorbid posttraumatic stress disorder (PTSD) and cocaine use disorder (CUD) are unknown. We aimed to develop an animal model of PTSD + CUD to examine the neurobiology underlying cocaine-seeking in the presence of PTSD comorbidity. Rats were exposed to cat urine once for 10-minutes and tested for anxiety-like behaviors one week later. Subsequently, rats underwent long-access (LgA) cocaine self-administration and extinction training. Rats were re-exposed to the trauma context and then immediately tested for cue primed reinstatement of cocaine-seeking. Plasma and brains were collected afterwards for corticosterone assays and real-time qPCR analysis. Urine-exposed (UE; n = 23) and controls not exposed to urine (Ctrl; n = 11) did not differ in elevated plus maze behavior, but UE rats displayed significantly reduced habituation of the acoustic startle response (ASR) relative to Ctrl rats. A median split of ASR habituation scores was used to classify stress-responsive rats. UE rats (n = 10) self-administered more cocaine on Day 1 of LgA than control rats (Ctrl + Coc; n = 8). Re-exposure to the trauma context prevented cocaine reinstatement only in stress-responsive rats. Ctrl + Coc rats had lower plasma corticosterone concentrations than Ctrls, and decreased gene expression of corticotropin releasing hormone (CRH) and Glcci1 in the hippocampus. Rats that self-administered cocaine displayed greater CRH expression in the amygdala that was independent of urine exposure. While we did not find that cat urine exposure induced a PTSD-like phenotype in our rats, the present study underscores the need to separate stressed rats into cohorts based on anxiety-like behavior in order to study individual vulnerability to PTSD + CUD. PMID- 27181612 TI - Imaging of Cerebral Amyloid Angiopathy with Bivalent (99m)Tc-Hydroxamamide Complexes. AB - Cerebral amyloid angiopathy (CAA), characterized by the deposition of amyloid aggregates in the walls of cerebral vasculature, is a major factor in intracerebral hemorrhage and vascular cognitive impairment and is also associated closely with Alzheimer's disease (AD). We previously reported (99m)Tc hydroxamamide ((99m)Tc-Ham) complexes with a bivalent amyloid ligand showing high binding affinity for beta-amyloid peptide (Abeta(1-42)) aggregates present frequently in the form in AD. In this article, we applied them to CAA-specific imaging probes, and evaluated their utility for CAA-specific imaging. In vitro inhibition assay using Abeta(1-40) aggregates deposited mainly in CAA and a brain uptake study were performed for (99m)Tc-Ham complexes, and all (99m)Tc-Ham complexes with an amyloid ligand showed binding affinity for Abeta(1-40) aggregates and very low brain uptake. In vitro autoradiography of human CAA brain sections and ex vivo autoradiography of Tg2576 mice were carried out for bivalent (99m)Tc-Ham complexes ([(99m)Tc]SB2A and [(99m)Tc]BT2B), and they displayed excellent labeling of Abeta depositions in human CAA brain sections and high affinity and selectivity to CAA in transgenic mice. These results may offer new possibilities for the development of clinically useful CAA-specific imaging probes based on the (99m)Tc-Ham complex. PMID- 27181614 TI - Bioavailability of Methadone After Sleeve Gastrectomy: A Planned Case Observation. AB - OBJECTIVE: Morbidly obese patients on opioid-replacement therapy may be at risk for treatment refusal with regard to bariatric surgery. However, patients on opioid replacement may have the personal skills to facilitate the lifestyle changes required for successful outcomes after bariatric surgery. This planned case observation assessed the effects of sleeve gastrectomy on the pharmacokinetic properties of methadone. METHODS: A white woman in her 40s on methadone maintenance therapy and with morbid obesity was referred for bariatric surgery. Serial blood samples for methadone concentration measurements were obtained before and at 5 days and 1, 7, and 11 months after surgery. FINDINGS: Serum methadone concentrations increased from before to 5 days after surgery and continued to increase for 7 months thereafter. The predose measurement at 11 months postoperatively suggests a further increase compared with the previous predose measurements. IMPLICATIONS: Clinicians should beware the potential for altered effects of methadone after bariatric surgery. We recommend that serum concentrations be routinely measured pre- and postoperatively, and that the dose be adjusted according to these measurements and regular clinical assessments. PMID- 27181615 TI - Clinical Utility of Basophil CD203c as a Biomarker for Predicting the Timing of Hypersensitivity Reaction in Carboplatin Rechallenge: Three Case Reports. AB - PURPOSE: Drug desensitization has been found to be an effective option for carboplatin rechallenge in patients at risk for severe hypersensitivity reaction. However, identifying such patients requires precise clinical tests. This study was performed to evaluate the clinical utility of basophil CD203c to predict the timing of carboplatin-induced severe hypersensitivity reaction. METHODS: Here we report on 3 patients undergoing a carboplatin-desensitization protocol at Mie University Hospital. For all patients, ex vivo exposure to carboplatin resulted in increased levels of activated basophils in a previous occurrence of carboplatin-induced severe hypersensitivity reaction. FINDINGS: Basophil activation test using carboplatin was returned to negative just before the first course of carboplatin-desensitization protocol in all patients, and they successfully received their first course of the protocol with no signs of anaphylaxis. However, for all of the patients, increased basophil activation was once again detected after subsequent readministration of carboplatin and grade 3 or 4 anaphylaxis developed. Basophil activation test coincided precisely with the timing of carboplatin-induced anaphylaxis in all patients. IMPLICATIONS: CD203c basophil activation testing might prove to be a reliable tool for risk stratification and clinical decision making for carboplatin desensitization in which severe hypersensitivity reaction is likely to occur. PMID- 27181616 TI - A two-step etching route to ultrathin carbon nanosheets for high performance electrical double layer capacitors. AB - Two-dimensional (2D) carbon materials have attracted intense research interest for electrical double layer capacitors (EDLCs) due to their high aspect ratio and large surface area. Herein, we propose an exfoliation-chlorination route for preparing ultrathin carbon nanosheets by using ternary layered carbide Ti3AlC2 as the precursor. Due to the large intersheet space of exfoliated layered carbide (MXene), the as-prepared carbon nanosheets exhibit a thickness of 3-4 nm and a large specific surface area of 1766 m(2) g(-1) with hierarchical porosity. These features significantly improve the ion-accessible surface area for charge storage and shorten the ion transport length in the thin dimension. As a result, the carbon nanosheets show a high specific capacitance (220 F g(-1) at 0.5 A g(-1)), remarkable high power capability (79% capacitance retention at 20 A g(-1)) when measured in a symmetrical two-electrode configuration in an aqueous electrolyte. The method described in this work provides a new route to prepare 2D electrode materials from a bulk precursor, thus exploiting their full potential for EDLCs. PMID- 27181617 TI - Size-Resolved Source Emission Rates of Indoor Ultrafine Particles Considering Coagulation. AB - Indoor ultrafine particles (UFP, <100 nm) released from combustion and consumer products lead to elevated human exposure to UFP. UFP emitted from the sources undergo aerosol transformation processes such as coagulation and deposition. The coagulation effect can be significant during the source emission due to high concentration and high mobility of nanosize particles. However, few studies have estimated size-resolved UFP source emission strengths while considering coagulation in their theoretical and experimental research work. The primary objective of this study is to characterize UFP source strength by considering coagulation in addition to other indoor processes (i.e., deposition and ventilation) in a realistic setting. A secondary objective is to test a hypothesis that size-resolved UFP source emission rates are unimodal and log normally distributed for three common indoor UFP sources: an electric stove, a natural gas burner, and a paraffin wax candle. Experimental investigations were performed in a full-scale test building. Size- and time-resolved concentrations of UFP ranging from 2 to 100 nm were monitored using a scanning mobility particle sizer (SMPS). Based on the temporal evolution of the particle size distribution during the source emission period, the size-dependent source emission rate was determined using a material-balance modeling approach. The results indicate that, for a given UFP source, the source strength varies with particle size and source type. The analytical model assuming a log-normally distributed source emission rate could predict the temporal evolution of the particle size distribution with reasonable accuracy for the gas stove and the candle. Including the effect of coagulation was found to increase the estimates of source strengths by up to a factor of 8. This result implies that previous studies on indoor UFP source strengths considering only deposition and ventilation might have largely underestimated the true values of UFP source strengths, especially for combustion due to the natural gas stove and the candle. PMID- 27181618 TI - Incidence, survival and cause-specific mortality in alcoholic liver disease: a population-based cohort study. AB - OBJECTIVE: We studied the incidence of severe ALD requiring hospitalization in Finland, and survival and causes of death among the ALD patients. METHODS: A cohort of 11,873 persons (8796 men and 3077 women) with diagnosis of ALD during the years 1996-2012 was identified from Finnish national Inpatient Register. The annual incidence of alcoholic hepatitis (AH) and alcoholic liver cirrhosis was calculated. The cohort was combined with the data from national Cause of Death Register of Statistics Finland. RESULTS: The incidence of alcoholic liver cirrhosis increased from 8.8/100,000 in year 2001 to 14.6/100,000 in year 2012 among men and from 2.4 to 4.2/100,000 among women. The incidence of AH increased from 3.7 to 6.5/100,000 among men and from 1.3 to 2.7/100,000 among women. The relative 5-year survival ratios of patients with alcoholic liver cirrhosis and AH were 29 and 50% among men and 38 and 52% among women, respectively. Out of 8440 deaths, 65% were due to alcoholic-related causes. The risk of death among ALD patients was increased in malignancies (SMR 6.82; 95% CI: 6.35-7.29), cardiovascular diseases (6.13; 5.74-6.52), respiratory diseases (7.86; 6.70 9.10), dementia (3.31; 2.41-4.44) and accidents and violence (11.12; 10.13 12.15). CONCLUSIONS: The incidence of AH and alcoholic liver cirrhosis is increasing. The survival is poor. Most deaths are alcohol-related and other common causes of excess deaths are cancers especially in the upper aerodigestive tract and cardiovascular, digestive and respiratory diseases as well as violence and accidents. PMID- 27181619 TI - Role of waist measures in addition to body mass index to assess the hypertension risk in children. AB - AIM: This study aimed to evaluate whether waist measures, including waist circumference (WC) and waist-to-height ratio (WHtR), can improve the ability of body mass index (BMI) to assess the hypertension risk when used as continuous variables. METHODS: In this cross-sectional study, 82 432 Chinese children aged 9 17 years were included. Elevated BP was defined using age-sex-and-height-specific references. Logistic regression model and area under the receiver operating characteristic curve (AUC) were performed after BMI and waist measures were converted into age-and-sex-based z-scores. RESULTS: WHtR, but not WC, was associated with elevated BP after adjusting for BMI, with the odds ratios ranging between 1.14 (95% confidence interval: 1.04, 1.25) and 1.30 (1.21, 1.39) for one unit increase in WHtR z-score. Combined use of BMI and WHtR z-scores showed a significantly larger AUC than BMI alone (p < 0.05), while joint use of BMI and WC was not better than BMI alone. CONCLUSION: WHtR, rather than WC, provided further information on hypertension risk beyond that provided by BMI alone when used as a continuous variable. This study suggests WHtR, in addition to BMI, should be included for the assessment of childhood adiposity in routine paediatric practice. PMID- 27181606 TI - Indacaterol-Glycopyrronium versus Salmeterol-Fluticasone for COPD. AB - BACKGROUND: Most guidelines recommend either a long-acting beta-agonist (LABA) plus an inhaled glucocorticoid or a long-acting muscarinic antagonist (LAMA) as the first-choice treatment for patients with chronic obstructive pulmonary disease (COPD) who have a high risk of exacerbations. The role of treatment with a LABA-LAMA regimen in these patients is unclear. METHODS: We conducted a 52 week, randomized, double-blind, double-dummy, noninferiority trial. Patients who had COPD with a history of at least one exacerbation during the previous year were randomly assigned to receive, by inhalation, either the LABA indacaterol (110 MUg) plus the LAMA glycopyrronium (50 MUg) once daily or the LABA salmeterol (50 MUg) plus the inhaled glucocorticoid fluticasone (500 MUg) twice daily. The primary outcome was the annual rate of all COPD exacerbations. RESULTS: A total of 1680 patients were assigned to the indacaterol-glycopyrronium group, and 1682 to the salmeterol-fluticasone group. Indacaterol-glycopyrronium showed not only noninferiority but also superiority to salmeterol-fluticasone in reducing the annual rate of all COPD exacerbations; the rate was 11% lower in the indacaterol glycopyrronium group than in the salmeterol-fluticasone group (3.59 vs. 4.03; rate ratio, 0.89; 95% confidence interval [CI], 0.83 to 0.96; P=0.003). The indacaterol-glycopyrronium group had a longer time to the first exacerbation than did the salmeterol-fluticasone group (71 days [95% CI, 60 to 82] vs. 51 days [95% CI, 46 to 57]; hazard ratio, 0.84 [95% CI, 0.78 to 0.91], representing a 16% lower risk; P<0.001). The annual rate of moderate or severe exacerbations was lower in the indacaterol-glycopyrronium group than in the salmeterol-fluticasone group (0.98 vs. 1.19; rate ratio, 0.83; 95% CI, 0.75 to 0.91; P<0.001), and the time to the first moderate or severe exacerbation was longer in the indacaterol glycopyrronium group than in the salmeterol-fluticasone group (hazard ratio, 0.78; 95% CI, 0.70 to 0.86; P<0.001), as was the time to the first severe exacerbation (hazard ratio, 0.81; 95% CI, 0.66 to 1.00; P=0.046). The effect of indacaterol-glycopyrronium versus salmeterol-fluticasone on the rate of COPD exacerbations was independent of the baseline blood eosinophil count. The incidence of adverse events and deaths was similar in the two groups. The incidence of pneumonia was 3.2% in the indacaterol-glycopyrronium group and 4.8% in the salmeterol-fluticasone group (P=0.02). CONCLUSIONS: Indacaterol glycopyrronium was more effective than salmeterol-fluticasone in preventing COPD exacerbations in patients with a history of exacerbation during the previous year. (Funded by Novartis; FLAME ClinicalTrials.gov number, NCT01782326.). PMID- 27181620 TI - Conscientious objection - to be or not to be. PMID- 27181621 TI - Prevalence of and risk factors for sexual dysfunction in young Chinese women according to the Female Sexual Function Index: an internet-based survey. AB - OBJECTIVES: Female sexual dysfunction (FSD) is a very common sexual health problem worldwide. The prevalence of FSD in Chinese women is, however, unknown. This is the first study to investigate a large number of young women throughout China via the internet, to determine the prevalence and types of FSD and to identify the risk factors for FSD. METHODS: The primary endpoint was the Female Sexual Function Index (FSFI) score, with additional questions on contraception, sexual activity, relationship stability, pregnancy and other factors which may influence sexual function. The online questionnaire was completed by women from 31 of the 34 Chinese provinces. RESULTS: A total of 1618 completed questionnaires were received, and 1010 were included in the analyses after screening (62.4%). The mean age of the respondents was 25.1 +/- 4.5 years. The mean total FSFI score was 24.99 +/- 4.60. According to FSFI definitions (cut-off score 26.55), 60.2% of women were at risk of FSD. Based on domain scores, 52 were considered at high risk of dysfunction for pain (5.1%), 35 for orgasm (3.5%), 33 for desire (3.3%), 20 for arousal (2.0%), 6 for satisfaction (0.6%) and 2 for lubrication (0.2%). CONCLUSIONS: The prevalence of FSFI scores indicating risk of sexual dysfunction was about 60% in Chinese women. An unstable relationship, pressure to become pregnant, non-use of contraception, negative self-evaluation of appearance and increasing age were significantly associated with FSD in young Chinese women. PMID- 27181622 TI - Anodic electrogenerated chemiluminescence behavior and the choline biosensing application of blue emitting conjugated polymer dots. AB - The anodic electrochemiluminescence (ECL) behavior of poly(9,9-dioctylfluorenyl 2,7-diyl) (PFO) dots was studied and applied in oxidoreductase-based ECL biosensing using Chox as the model enzyme. PMID- 27181623 TI - Is There a Difference in Cost Between Standard and Virtual Surgical Planning for Orthognathic Surgery? AB - PURPOSE: Virtual surgical planning (VSP) and 3-dimensional printing of surgical splints are becoming the standard of care for orthognathic surgery, but costs have not been thoroughly evaluated. The purpose of this study was to compare the cost of VSP and 3-dimensional printing of splints ("VSP") versus that of 2 dimensional cephalometric evaluation, model surgery, and manual splint fabrication ("standard planning"). MATERIALS AND METHODS: This is a retrospective cohort study including patients planned for bimaxillary surgery from January 2014 to January 2015 at Massachusetts General Hospital. Patients were divided into 3 groups by case type: symmetric, nonsegmental (group 1); asymmetric (group 2); and segmental (group 3). All cases underwent both VSP and standard planning with times for all activities recorded. The primary and secondary predictor variables were method of treatment planning and case type, respectively. Time-driven activity-based micro-costing analysis was used to quantify the differences in cost. Results were analyzed using a paired t test and analysis of variance. RESULTS: The sample included 43 patients (19 in group 1, 17 in group 2, and 7 in group 3). The average times and costs were 194 +/- 14.1 minutes and $2,765.94, respectively, for VSP and 540.9 +/- 99.5 minutes and $3,519.18, respectively, for standard planning. For the symmetric, nonsegmental group, the average times and costs were 188 +/- 17.8 minutes and $2,700.52, respectively, for VSP and 524.4 +/ 86.1 minutes and $3,380.17, respectively, for standard planning. For the asymmetric group, the average times and costs were 187.4 +/- 10.9 minutes and $2,713.69, respectively, for VSP and 556.1 +/- 94.1 minutes and $3,640.00, respectively, for standard planning. For the segmental group, the average times and costs were 208.8 +/- 13.5 minutes and $2,883.62, respectively, for VSP and 542.3 +/- 118.4 minutes and $3,537.37, respectively, for standard planning. All time and cost differences were statistically significant (P < .001). CONCLUSIONS: The results of this study indicate that VSP for bimaxillary orthognathic surgery takes significantly less time and is less expensive than standard planning for the 3 types of cases analyzed. PMID- 27181625 TI - The effect of time in use on the display performance of the iPad. AB - OBJECTIVE: The aim of this study was to evaluate changes to the luminance, luminance uniformity and conformance to the digital imaging and communication in medicine greyscale standard display function (GSDF) as a function of time in use for the iPad. METHODS: Luminance measurements of the American Association of Physicists in Medicine (AAPM) Group 18 task group (TG18) luminance uniformity and luminance test patterns (TG18-UNL and TG18-LN8) were performed using a calibrated near-range luminance meter. Nine sets of measurements were taken, where the time in use of the iPad ranged from 0 to 2500 h. RESULTS: The maximum luminance (Lmax) of the display decreased (367-338 cdm(-2)) as a function of time. The minimum luminance remained constant. The maximum non-uniformity coefficient was 11%. Luminance uniformity decreased slightly as a function of time in use. The conformance of the iPad deviated from the GSDF curve at commencement of use. Deviation did not increase as a function of time in use. CONCLUSION: This study has demonstrated that the iPad display exhibits luminance degradation typical of liquid crystal displays. The Lmax of the iPad fell below the American College of Radiology-AAPM-Society of Imaging Informatics in Medicine recommendations for primary displays (>350 cdm(-2)) at approximately 1000 h in use. The Lmax recommendation for secondary displays (>250 cdm(-2)) was exceeded during the entire study. The maximum non-uniformity coefficient did not exceed the recommendations for either primary or secondary displays. The deviation from the GSDF exceeded the recommendations of the TG18 for use as either a primary or secondary display. ADVANCES IN KNOWLEDGE: The brightness, uniformity and contrast response are reasonably stable over the useful lifetime of the device; however, the device fails to meet the contrast response standard for either a primary or secondary display. PMID- 27181624 TI - Morbidity and Mortality Rates After Maxillomandibular Advancement for Treatment of Obstructive Sleep Apnea. AB - PURPOSE: To compare morbidity and mortality rates in obstructive sleep apnea (OSA) versus dentofacial deformity (DFD) patients undergoing equivalent maxillofacial surgical procedures. PATIENTS AND METHODS: Patients with OSA who underwent maxillomandibular advancement with genial tubercle advancement in the Massachusetts General Hospital Department of Oral and Maxillofacial Surgery from December 2002 to June 2011 were matched to patients with DFD undergoing similar maxillofacial procedures during the same period. They were compared regarding demographic variables, medical comorbidities, perioperative management, intraoperative complications, early and late postoperative complications, and mortality rate. RESULTS: A study group of 28 patients with OSA and a control group of 26 patients with DFD were compared. The patients with OSA were older (41.9 +/- 12.5 years vs 21.7 +/- 8.6 years), had a higher American Society of Anesthesiologists classification (2.0 +/- 0.5 vs 1.3 +/- 0.6), and had a higher body mass index (29.6 +/- 4.7 kg/m(2) vs 23.0 +/- 3.1 kg/m(2)). They also had a greater number of medical comorbidities (2.4 +/- 2.3 vs 0.7 +/- 1.0). More OSA patients than DFD patients had complications (28 [100%] vs 19 [73%], P = .003), and the total number of complications in the OSA group was higher (108 vs 33, P < .001). Of the complications, 13.9% in the OSA group and 3.0% in the DFD group were classified as major. The absolute risk of a complication was 3.9 for the OSA group versus 1.3 for the DFD group. The relative risk of complications in OSA patients compared with DFD patients was 3.0. No difference in mortality rate was found. CONCLUSIONS: The patients in the OSA group were older, had more comorbidities, and ultimately had a greater number of early, late, minor, and major complications than those in the DFD group. The incidence of death in both groups was zero. Maxillomandibular advancement appears to be a safe procedure regarding mortality rate, but OSA patients should be counseled preoperatively regarding the relative increased risk of complications. PMID- 27181626 TI - Tuning the composition of Bi x W y O nanorods towards zero bias PEC water splitting. AB - A unique co-oblique angle deposition method was used to create nanorod arrays of mixed phase Bi2O3/WO3/Bi2WO6 with varying atomic ratios of Bi to W. The effect of the tuning on the resulting nanostructures was characterized by EDX, SEM, XRD, optical transmission, specular reflection, and diffuse reflection spectroscopy. Samples with different Bi:W atomic ratio had a wide range of morphology and composition due to the surface mobility of deposited bismuth and its volume expansion during oxidation. Their photocatalytic and photoelectrochemical properties were investigated by methylene blue degradation and photo-generated current respectively. The sample with 38 at.% Bi showed the highest photodecay rates as well as the maximum photocurrent density, 4.3 MUA cm(-2), at a bias potential of 600 mV versus Ag/AgCl (3M KCl); while the sample with 50 at.% Bi exhibited a high photocurrent density of 0.35 MUA cm(-2) at zero bias potential, which indicates that varying the composition and mixed crystal phases of different oxides with appropriate band gaps and locations could hold the key to a visible light driven, zero bias potential, photoelectrochemical cell. PMID- 27181627 TI - Fatness of female field hockey players: Comparison of estimates with different methods. AB - The aim of the study was to compare relative body fat (% fat) in female field hockey players using several methods with dual-energy X-ray absorptiometry (DXA) as the reference. Participants were 31 Polish hockey players 16-30 years of age, 17 national and 14 youth level. Percent body fat was estimated by DXA (reference method), conventional and segmental bioelectrical impedance analysis (BIA), and predicted from skinfolds (SKF). National and youth team members did not differ in estimated body fat. Correlations between BIA and skinfold estimates of % fat and DXA % fat though significant, were moderate. Both % fat SKF and % fat SBIA differed significantly from % fat DXA, while estimated % fat BIA and % fat DXA did not differ. Limits of agreement were narrow for conventional BIA (-1.20 to 1.71% fat), followed by segmental BIA (3.72-6.09% fat) and broadest for SKF (5.97 9.28% fat). Differences between DXA % fat and estimated % fat with SKF and SBIA increased from the leanest to fattest athletes, whereas conventional BIA overestimated % fat relative to DXA in the small sample of individuals with low relative fatness and underestimated % fat in individuals with elevated relative fatness. Estimated % fat from conventional BIA most closely approximated DXA % fat in this sample of female field hockey players suggesting that the method may be suitable for field surveys to monitor body composition during the season. PMID- 27181628 TI - Chemotherapeutic treatment is associated with Notch1 induction in cutaneous T cell lymphoma. AB - The Notch pathway is important for survival of cutaneous T-cell lymphoma (CTCL) cells. We investigated the effect of chemotherapy (doxorubicin, etoposide, and gemcitabine) and radiation modalities on Notch signaling in CTCL cell lines. Chemotherapy induced Notch1 expression at the mRNA and protein level in MyLa2000 and Hut78. Upregulation of well-established Notch targets supported the functional activity of Notch1. Transfection of Notch1 siRNA into MyLa2000 cells was not able to suppress the effects of chemotherapy on Notch1 activation significantly. Notch1 knockdown in combination with doxorubicin, etoposide, or gemcitabine compared to chemotherapy alone decreased cell viability by 12, 20, and 26%, respectively (p < 0.05). Additionally, X-rays (in MyLa2000 but not SeAx) and psoralen plus UVA (PUVA) (in MyLa2000, Hut78, and SeAx) increased the expression of Notch1 family members. Our results indicate that CTCL cells activate the Notch pathway in vitro in response to chemotherapy and radiation modalities as a possible protective mechanism. PMID- 27181629 TI - Identification of rs671, a common variant of ALDH2, as a gout susceptibility locus. AB - Gout is a common disease resulting from hyperuricemia. Recently, a genome-wide association study identified an association between gout and a single nucleotide polymorphism (SNP) rs2188380, located on an intergenic region between MYL2 and CUX2 on chromosome 12. However, other genes around rs2188380 could possibly be gout susceptibility genes. Therefore, we performed a fine-mapping study of the MYL2-CUX2 region. From 8,595 SNPs in the MYL2-CUX2 region, 9 tag SNPs were selected, and genotyping of 1,048 male gout patients and 1,334 male controls was performed by TaqMan method. Eight SNPs showed significant associations with gout after Bonferroni correction. rs671 (Glu504Lys) of ALDH2 had the most significant association with gout (P = 1.7 * 10(-18), odds ratio = 0.53). After adjustment for rs671, the other 8 SNPs no longer showed a significant association with gout, while the significant association of rs671 remained. rs671 has been reportedly associated with alcohol drinking behavior, and it is well-known that alcohol drinking elevates serum uric acid levels. These data suggest that rs671, a common functional SNP of ALDH2, is a genuine gout-associated SNP in the MYL2-CUX2 locus and that "A" allele (Lys) of rs671 plays a protective role in the development of gout. PMID- 27181634 TI - Inhibitory effects of geraniin on LPS-induced inflammation via regulating NF kappaB and Nrf2 pathways in RAW 264.7 cells. AB - Geraniin, a major polyphenolic compound of Geranium sibiricum L, has long been used as an important Chinese herbal medicine for the treatment of a variety of inflammatory pathologies. However, the underlying anti-inflammatory molecular mechanisms of this compound are not clear. The aim of the present study was to investigate the anti-inflammatory activities of geraniin and elucidate the underlying mechanisms. The anti-inflammatory effects of geraniin were studied by using lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Geraniin suppressed the inducible nitric oxide synthase (iNOS) expression, and inhibited reactive oxygen species (ROS) production. Subsequent studies demonstrated that geraniin effectively reduced production of NO and pro-inflammatory cytokines. These effects were mediated by impaired translocation of nuclear factor (NF)-kappaB and inhibition of the phosphorylation of Akt in LPS-stimulated RAW 264.7 cells. Furthermore, geraniin induced heme oxygenase-1 (HO-1) expression via activation of transcription factor Nrf2. This study gives scientific evidence that geraniin inhibits the LPS-induced expression of inflammatory mediators via suppression of Akt-mediated NF-kappaB pathway as well as up-regulation of Nrf2/HO-1 pathway, indicating that geraniin has a potential application in inflammatory conditions. PMID- 27181630 TI - Marine cyanobacteria-derived serotonin receptor 2C active fraction induces psychoactive behavioral effects in mice. AB - CONTEXT: Marine cyanobacteria offer a robust resource for natural products drug discovery due to the secondary metabolites they produce. OBJECTIVE: To identify novel cyanobacterial compounds that exhibit CNS psychoactive effects. MATERIALS AND METHODS: Cyanobacteria were collected from Las Perlas Archipelago, Panama and subjected to dichloromethane/methanol extraction and fractionation by column chromatography before being screened for affinity against a panel of CNS targets. A 50:50 ethyl acetate:methanol fraction of one cyanobacterial extract (2064H) was subjected to HPLC and the major peak was isolated (2064H3). At a dose of 20 MUg per animal, 2064H and 2064H3 were tested in mice using behavioral assays that included the forced swim, open field and formalin tests. RESULTS: 2064H was shown to bind to the serotonin 2C (5-HT2C) receptor, a known target for depression and pain treatment. 2064H showed 59.6% inhibition of binding of [3H]-mesulergine with an IC50 value of 179 ng/mL and did not show inhibition of binding greater than 45% with any other receptors tested. Both 2064H and 2064H3 decreased immobility time in the first minute of the tail suspension test. 2064H increased time, distance and number of entries in the center region in the first half of the open field test. 2064H increased overall nocifensive behaviors in the formalin test. DISCUSSION AND CONCLUSION: Overall, manipulating the 5-HT2C receptor with these receptor-specific ligands derived from cyanobacteria altered pain, depression and anxiety-like behaviors, illustrating the importance of this receptor in affective behaviors. These results demonstrate the potential of cyanobacteria as a source for CNS active compounds. PMID- 27181635 TI - The naturally occurring alpha-tocopherol stereoisomer RRR-alpha-tocopherol is predominant in the human infant brain. AB - alpha-Tocopherol is the principal source of vitamin E, an essential nutrient that plays a crucial role in maintaining healthy brain function. Infant formula is routinely supplemented with synthetic alpha-tocopherol, a racaemic mixture of eight stereoisomers with less bioactivity than the natural stereoisomer RRR-alpha tocopherol. alpha-Tocopherol stereoisomer profiles have not been previously reported in the human brain. In the present study, we analysed total alpha tocopherol and alpha-tocopherol stereoisomers in the frontal cortex (FC), hippocampus (HPC) and visual cortex (VC) of infants (n 36) who died of sudden infant death syndrome or other conditions. RRR-alpha-tocopherol was the predominant stereoisomer in all brain regions (P<0.0001) and samples, despite a large intra-decedent range in total alpha-tocopherol (5-17 MUg/g). Mean RRR-alpha tocopherol concentrations in FC, HPC and VC were 10.5, 6.8 and 5.5 MUg/g, respectively. In contrast, mean levels of the synthetic stereoisomers were RRS, 1 1.5; RSR, 0.8-1.0; RSS, 0.7-0.9; and Sigma2S 0.2-0.3 MUg/g. Samples from all but two decedents contained measurable levels of the synthetic stereoisomers, but the intra-decedent variation was large. The ratio of RRR:the sum of the synthetic 2R stereoisomers (RRS+RSR+RSS) averaged 2.5, 2.3 and 2.4 in FC, HPC and VC, respectively, and ranged from 1 to at least 4.7, indicating that infant brain discriminates against synthetic 2R stereoisomers in favour of RRR. These findings reveal that RRR-alpha-tocopherol is the predominant stereoisomer in infant brain. These data also indicate that the infant brain discriminates against the synthetic 2R stereoisomers, but is unable to do so completely. On the basis of these findings, investigation into the impact of alpha-tocopherol stereoisomers on neurodevelopment is warranted. PMID- 27181637 TI - Effects of maternal hypothyroidism during pregnancy on learning, memory and hippocampal BDNF in rat pups: Beneficial effects of exercise. AB - Hypothyroidism during early development leads to numerous morphological, biochemical and functional changes in developing brain. In this study, we investigated the effects of voluntary and treadmill exercise on learning, memory and hippocampal BDNF levels in both hypothyroid male and female rat pups. To induce hypothyroidism in the mothers, 6-propyl-2-thiouracil (PTU) was added to their drinking water (100mg/L) from their embryonic day 6 to their postnatal day (PND) 21. For 14days, from PNDs 31 to 44, the rat pups were trained with one of the two different exercise protocols, namely the mild treadmill exercise and the voluntary wheel exercise. On PNDs 45-52, a water maze was used for testing their learning and memory ability. The rats were sacrificed one day later and their BDNF levels were then measured in the hippocampus. The findings of the present study indicate that hypothyroidism during the fetal period and the early postnatal period is associated with the impairment of spatial learning and memory and reduced hippocampal BDNF levels in both male and female rat offspring. Both the short-term treadmill exercise and the voluntary wheel exercise performed during the postnatal period reverse the behavioral and neurochemical deficits induced by developmental thyroid hormone insufficiency in both male and female rat offspring. The findings of this study thus demonstrate a marked reversibility of both behavioral and neurochemical disorders induced by developmental thyroid hormone insufficiency through the performance of exercise. PMID- 27181638 TI - Hematocrit analysis through the use of an inexpensive centrifugal polyester-toner device with finger-to-chip blood loading capability. AB - Hematocrit (HCT) measurements are important clinical diagnostic variables that help physicians diagnose and treat various medical conditions, ailments, and diseases. In this work, we present the HCT Disc, a centrifugal microdevice fabricated by a Print, Cut and Laminate (PCL) method to generate a 12-sample HCT device from materials costing <0.5 USD (polyester and toner or PeT). Following introduction from a drop of blood (finger stick), whole blood metering and cell sedimentation are controlled by centrifugal force, only requiring a CD player motor as external hardware and, ultimately, a cell phone for detection. The sedimented volume from patient blood in the HCT Disc was analyzed using a conventional scanner/custom algorithm for analysis of the image to determine a hematocrit value, and these were compared to values generated in a clinical laboratory, which correlated well. To enhance portability and assure simplicity of the HCT measurement, values from image analysis by a cell phone using a custom application was compared to the scanner. Fifteen samples were analyzed with cell phone image analysis system and were found to be within 4% of the HCT values determined in the clinical lab. We demonstrate the feasibility of the PeT device for HCT measurement, and highlight its uniquely low cost (<0.5 USD), speed (sample-to-answer <8 min), multiplexability (12 samples), low volume whole blood requirement (<3 MUL), rotation speeds (<4000 rpm) needed for effective measurement as well as the direct finger-to-chip sample loading capability. PMID- 27181639 TI - Is the solvation parameter model or its adaptations adequate to account for ionic interactions when characterizing stationary phases for drug impurity profiling with supercritical fluid chromatography? AB - Nine commercially available polar and aromatic stationary phases were characterized under supercritical fluid chromatographic (SFC) conditions. Retention data of 64 pharmaceutical compounds was acquired to generate models based on the linear solvation energy relationship (LSER) approach. Previously, adaptation of the LSER model was done in liquid chromatography by the addition of two solute descriptors to describe the influence of positive (D(+)) and negative (D(-)) charges on the retention of ionized compounds. In this study, the LSER models, with and without the ionization terms for acidic and basic solutes, were compared. The improved fits obtained for the modified models support inclusion of the D(+) and D(-) terms for pharmaceutical compounds. Moreover, the statistical significance of the new terms in the models indicates the importance of ionic interactions in the retention of pharmaceutical compounds in SFC. However, unlike characterization through the retention profiles, characterization of the stationary phases by modelling never explains the retention variance completely and thus seems less appropriate. PMID- 27181636 TI - Usp9x-deficiency disrupts the morphological development of the postnatal hippocampal dentate gyrus. AB - Within the adult mammalian brain, neurogenesis persists within two main discrete locations, the subventricular zone lining the lateral ventricles, and the hippocampal dentate gyrus. Neurogenesis within the adult dentate gyrus contributes to learning and memory, and deficiencies in neurogenesis have been linked to cognitive decline. Neural stem cells within the adult dentate gyrus reside within the subgranular zone (SGZ), and proteins intrinsic to stem cells, and factors within the niche microenvironment, are critical determinants for development and maintenance of this structure. Our understanding of the repertoire of these factors, however, remains limited. The deubiquitylating enzyme USP9X has recently emerged as a mediator of neural stem cell identity. Furthermore, mice lacking Usp9x exhibit a striking reduction in the overall size of the adult dentate gyrus. Here we reveal that the development of the postnatal SGZ is abnormal in mice lacking Usp9x. Usp9x conditional knockout mice exhibit a smaller hippocampus and shortened dentate gyrus blades from as early as P7. Moreover, the analysis of cellular populations within the dentate gyrus revealed reduced stem cell, neuroblast and neuronal numbers and abnormal neuroblast morphology. Collectively, these findings highlight the critical role played by USP9X in the normal morphological development of the postnatal dentate gyrus. PMID- 27181640 TI - Development of a mediated whole cell-based electrochemical biosensor for joint toxicity assessment of multi-pollutants using a mixed microbial consortium. AB - Since most risk assessment for toxicants is based on individual single-species test, the deduction of such results to ecosystem evaluation is afflicted with uncertainties. Herein, we successfully developed a p-benzoquinone mediated whole cell electrochemical biosensor for multi-pollutants toxicological analysis by co immobilizing mixed strains of microorganism, including Escherichia coli (gram negative bacteria), Bacillus subtilis (gram-positive bacteria) and Saccharomyces cerevisiae (fungus). The individual and combined toxicities of heavy metal ions (Cu(2+), Cd(2+)), phenol (3,5-dichlorophenol) and pesticides (Ametryn, Acephate) were examined. The experimental results showed that the order of toxicity for individual toxicant was ranked as Cu(2+) > 3,5-dichlorophenol (DCP) > Ametryn > Cd(2+) > Acephate. Then the toxic unit (TU) model was applied to determine the nature of toxicological interaction of the toxicants which can be classified as concentration additive (IC50mix = 1TU), synergistic (IC50mix < 1TU) and antagonistic (IC50mix > 1TU) responses. The binary combination of Cu(2+) + Cd(2+), Cu(2+) + DCP, Cu(2+) + Acephate, DCP + Acephate, Acephate + Ametryn were analyzed and the three kind of joint toxicity effects (i.e. additive, synergistic and antagonistic) mentioned above were observed according to the dose-response relationship. The results indicate that the whole-cell electrochemical biosensor based on mixed microbial consortium is more reasonable to reflect the joint biotoxicity of multi-pollutants existing in real wastewater, and combined effects of toxicants is extremely necessary to be taken into account in ecological risk assessment. Thus, present study has provided a promising approach to the quality assessment of wastewater and a reliable way for early risk warning of acute biotoxicity. PMID- 27181641 TI - Electrochemical detection of DNA 3'-phosphatases based on surface-extended DNA nanotail strategy. AB - Determination of DNA dephosphorylation is of great value due to its vital role in many cellular processes. Here we report a surface-extended DNA nanotail strategy for simple and ultrasensitive detection of DNA 3'-phosphatases by terminal deoxynucleotidyl transferase (TdT) mediated signal amplification. In this work, DNA probes labeled with thiols at their 5' terminals and phosphoryls at 3' terminals are immobilized on gold electrode and are used as substrates for DNA 3' phosphatases, taking T4 polynucleotide kinase phosphatase (T4PNKP) as an example. T4PNKP can catalyze the dephosphorylation reaction of the substrate DNA, followed by the formation of a long DNA strand by TdT on its 3' terminal hydroxyl, leading to an evident chronocoulometry signal enhancement. The proposal presents a considerable analytical performance with low detection limit and wide linear range, making it promise to be applied in the fields of DNA dephosphorylation related processes, drug discovery, and clinical diagnostics. PMID- 27181642 TI - Development of natural sorbent based micro-solid-phase extraction for determination of phthalate esters in milk samples. AB - In the present study, a natural sorbent based micro-solid phase extraction (MU SPE) was developed for determination of phthalate esters in milk samples. For the first time, an efficient and cost effective natural material (seed powder of Moringa oleifera) was employed as sorbent in MU-SPE. The sorbent was found to be naturally enriched with variety of functional groups and having a network of interconnected fibers. This method of extraction integrates different steps such as removal of proteins and fatty stuff, extraction and pre-concentration of target analytes into a single step. Thirteen phthalate esters were selected as target compounds for the development and evaluation of method. Some key parameters affecting the extraction efficiency were optimized, including selection of membrane, selection and amount of sorbent, extraction time, desorption solvent, volume of desorption solvent, desorption time and effect of salt addition. Under the optimum conditions, very good linearity was achieved for all the analytes with coefficient of determinations (R(2)) ranging between 0.9768 and 0.9977. The limits of detection ranged from 0.01 to 1.2 MUg L(-1). Proposed method showed satisfactory reproducibility with relative standard deviations ranging from 3.6% to 10.2% (n = 7). Finally, the developed method was applied to tetra pack and bottled milk samples for the determination of phthalate esters. The performance of natural sorbent based MU-SPE was better or comparable to the methods reported in the literature. PMID- 27181643 TI - Sorptive thin film microextraction followed by direct solid state spectrofluorimetry: A simple, rapid and sensitive method for determination of carvedilol in human plasma. AB - A poly acrylate-ethylene glycol (PA-EG) thin film is introduced for the first time as a novel polar sorbent for sorptive extraction method coupled directly to solid-state spectrofluorimetry without the necessity of a desorption step. The structure, polarity, fluorescence property and extraction performance of the developed thin film were investigated systematically. Carvedilol was used as the model analyte to evaluate the proposed method. The entire procedure involved one step extraction of carvedilol from plasma using PA-EG thin film sorptive phase without protein precipitation. Extraction variables were studied in order to establish the best experimental conditions. Optimum extraction conditions were the followings: stirring speed of 1000 rpm, pH of 6.8, extraction temperature of 60 degrees C, and extraction time of 60 min. Under optimal conditions, extraction of carvedilol was carried out in spiked human plasma; and the linear range of calibration curve was 15-300 ng mL(-1) with regression coefficient of 0.998. Limit of detection (LOD) for the method was 4.5 ng mL(-1). The intra- and inter-day accuracy and precision of the proposed method were evaluated in plasma sample spiked with three concentration levels of carvedilol; yielding a recovery of 91-112% and relative standard deviation of less than 8%, respectively. The established procedure was successfully applied for quantification of carvedilol in plasma sample of a volunteer patient. The developed PA-EG thin film sorptive phase followed by solid-state spectrofluorimetric method provides a simple, rapid and sensitive approach for the analysis of carvedilol in human plasma. PMID- 27181644 TI - Anti-idiotypic nanobody-alkaline phosphatase fusion proteins: Development of a one-step competitive enzyme immunoassay for fumonisin B1 detection in cereal. AB - A rapid and sensitive one-step competitive enzyme immunoassay for the detection of FB1 was developed. The anti-idiotypic nanobody-alkaline phosphatase (Ab2beta Nb-AP) was validated by the AP enzyme activity and the properties of bounding to anti-FB1-mAb (3F11) through colorimetric and chemiluminescence analyses. The 50% inhibitory concentration and the detection limit (LOD) of colorimetric enzyme linked immunosorbent assay (ELISA) for FB1 were 2.69 and 0.35 ng mL(-1), respectively, with a linear range of 0.93-7.73 ng mL(-1). The LOD of the chemiluminescence ELISA (CLIA) was 0.12 ng mL(-1), and the IC50 was 0.89 +/- 0.09 ng mL(-1) with a linear range of 0.29-2.68 ng mL(-1). Compared with LC-MS/MS, the results of this assay indicated the reliability of the Ab2beta-Nb-AP fusion protein based one-step competitive immunoassay for monitoring FB1 contamination in cereals. The Ab2beta-Nb-AP fusion proteins have the potential to replace chemically-coupled probes in competitive enzyme immunoassay systems. PMID- 27181645 TI - Chelate titrations of Ca(2+) and Mg(2+) using microfluidic paper-based analytical devices. AB - We developed microfluidic paper-based analytical devices (MUPADs) for the chelate titrations of Ca(2+) and Mg(2+) in natural water. The MUPAD consisted of ten reaction zones and ten detection zones connected through narrow channels to a sample zone located at the center. Buffer solutions with a pH of 10 or 13 were applied to all surfaces of the channels and zones. Different amounts of ethylenediaminetetraacetic acid (EDTA) were added to the reaction zones and a consistent amount of a metal indicator (Eriochrome Black T or Calcon) was added to the detection zones. The total concentrations of Ca(2+) and Mg(2+) (total hardness) in the water were measured using a MUPAD containing a buffer solution with a pH of 10, whereas only Ca(2+) was titrated using a MUPAD prepared with a potassium hydroxide solution with a pH of 13. The MUPADs permitted the determination of Ca(2+) and Mg(2+) in mineral water, river water, and seawater samples within only a few minutes using only the naked eye-no need of instruments. PMID- 27181646 TI - Collision cross section prediction of deprotonated phenolics in a travelling-wave ion mobility spectrometer using molecular descriptors and chemometrics. AB - The combination of ion mobility and mass spectrometry (MS) affords significant improvements over conventional MS/MS, especially in the characterization of isomeric metabolites due to the differences in their collision cross sections (CCS). Experimentally obtained CCS values are typically matched with theoretical CCS values from Trajectory Method (TM) and/or Projection Approximation (PA) calculations. In this paper, predictive models for CCS of deprotonated phenolics were developed using molecular descriptors and chemometric tools, stepwise multiple linear regression (SMLR), principal components regression (PCR), and partial least squares regression (PLS). A total of 102 molecular descriptors were generated and reduced to 28 after employing a feature selection tool, composed of mass, topological descriptors, Jurs descriptors and shadow indices. Therefore, the generated models considered the effects of mass, 3D conformation and partial charge distribution on CCS, which are the main parameters for either TM or PA (only 3D conformation) calculations. All three techniques yielded highly predictive models for both the training (R(2)SMLR = 0.9911; R(2)PCR = 0.9917; R(2)PLS = 0.9918) and validation datasets (R(2)SMLR = 0.9489; R(2)PCR = 0.9761; R(2)PLS = 0.9760). Also, the high cross validated R(2) values indicate that the generated models are robust and highly predictive (Q(2)SMLR = 0.9859; Q(2)PCR = 0.9748; Q(2)PLS = 0.9760). The predictions were also very comparable to the results from TM calculations using modified mobcal (N2). Most importantly, this method offered a rapid (<10 min) alternative to TM calculations without compromising predictive ability. These methods could therefore be used in routine analysis and could be easily integrated to metabolite identification platforms. PMID- 27181647 TI - MALDI-MS analysis of sialylated N-glycan linkage isomers using solid-phase two step derivatization method. AB - Sialic acids usually locate at the terminal of many glycan structures in either alpha(2,3) or alpha(2,6) linkage, playing different roles in various biological and pathological processes. Several linkage specific carboxyl derivatization methods have been reported to discriminate between alpha(2,3) and alpha(2,6) linked sialic acids by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). Among them, ethyl esterification was recently reported to achieve linkage specific derivatization between alpha(2,3) and alpha(2,6) linked sialic acids with good selectivity. However, the method suffered from the instability of the generated lactones and byproducts of the derivatives. To overcome these shortcomings, a solid-phase two step derivatization method was introduced to convert the alpha(2,6)-linked sialic acid into ethyl esters and the alpha(2,3)-inked counterparts into N-methyl amides, respectively. Under the optimized derivatization conditions, our method was able to achieve accurate relative quantification of N-glycan as well as their corresponding sialylated linkage types, superior to the ethyl esterification method. The solid phase derivatization strategy was further applied to investigate N-glycans from biosimilar antibody drug and human serum from patients and healthy volunteers. This method has the potential to be used in the biomarker discovery and pharmaceutical industry. PMID- 27181648 TI - Computational design and multivariate optimization of an electrochemical metoprolol sensor based on molecular imprinting in combination with carbon nanotubes. AB - This work describes the development of an electrochemical sensor based on a new molecularly imprinted polymer for detection of metoprolol (MTP) at ultra-trace level. The polypyrrole (PPy) was electrochemically synthesized on the tip of a pencil graphite electrode (PGE) which modified whit functionalized multi-walled carbon nanotubes (MWCNTs). The fabrication process of the sensor was characterized by cyclic voltammetry (CV) and the measurement process was carried out by differential pulse voltammetry (DPV). A computational approach was used to screening functional monomers and polymerization solvent for rational design of molecularly imprinted polymer (MIP). Based on computational results, pyrrole and water were selected as functional monomer and polymerization solvent, respectively. Several significant parameters controlling the performance of the MIP sensor were examined and optimized using multivariate optimization methods such as Plackett-Burman design (PBD) and central composite design (CCD). Under the selected optimal conditions, MIP sensor was showed a linear range from 0.06 to 490 MUmol L(-1) MTP, a limit of detection of 2.88 nmol L(-1), a highly reproducible response (RSD 3.9%) and a good selectivity in the presence of structurally related molecules. Furthermore, the applicability of the method was successfully tested with determination of MTP in real samples (tablet, and serum). PMID- 27181649 TI - Fabrication of a liquid-gated enzyme field effect device for sensitive glucose detection. AB - This study presents fabrication of a liquid-gated enzyme field effect device and its implementation as a glucose biosensor. The device consisted of four electrodes on a glass substrate with a channel functionalized by carboxylated multi-walled carbon nanotubes-polyaniline nanocomposite (MWCNTCOOH/PAn) and glucose oxidase. The resistance of functionalized channel increased with increasing the concentration of glucose when an electric field was applied to the liquid gate. The most effective and stable performance was obtained at the applied electric field of 100 mV. The device resistance, R, exhibited a linear relationship with the logarithm of glucose concentration in the range between 0.005 and 500 mM glucose. The detection limit (S/N = 3) for glucose was about 0.5 MUM. Large effective area and good conductivity properties of MWCNTCOOH/PAn nanocomposite were the key features of the fabricated sensitive and stable glucose biosensor. PMID- 27181650 TI - Sensing lymphoma cells based on a cell-penetrating/apoptosis-inducing/electron transfer peptide probe. AB - To electrochemically sense lymphoma cells (U937), we fabricated a multifunctional peptide probe that consists of cell-penetrating/apoptosis-inducing/electron transfer peptides. Electron-transfer peptides derive from cysteine residue combined with the C-terminals of four tyrosine residues (Y4). A peptide whereby Y4C is bound to the C-terminals of protegrin 1 (RGGRLCYCRRRFCVCVGR-NH2) is known to be an apoptosis-inducing agent against U937 cells, and is referred to as a peptide-1 probe. An oxidation response of the peptide-1 probe has been observed due to a phenolic hydroxyl group, and this response is decreased by the uptake of the peptide probe into the cells. To improve the cell membrane permeability against U937 cells, the RGGR at the N-terminals of the peptide-1 probe was replaced by RRRR (peptide-2 probe). In contrast, RNRCKGTDVQAWY4C (peptide-3 probe), which recognizes ovalbumin, was constructed as a control. Compared with the other probes, the change in the peak current of the peptide-2 probe was the greatest at low concentrations and occurred in a short amount of time. Therefore, the cell membrane permeability of the peptide-2 probe was increased based on the arginine residues and the apoptosis-inducing peptides. The peak current was linear and ranged from 100 to 1000 cells/ml. The relative standard deviation of 600 cells/ml was 5.0% (n = 5). Furthermore, the membrane permeability of the peptide probes was confirmed using fluorescent dye. PMID- 27181677 TI - Three novel approaches to structural identifiability analysis in mixed-effects models. AB - BACKGROUND AND OBJECTIVE: Structural identifiability is a concept that considers whether the structure of a model together with a set of input-output relations uniquely determines the model parameters. In the mathematical modelling of biological systems, structural identifiability is an important concept since biological interpretations are typically made from the parameter estimates. For a system defined by ordinary differential equations, several methods have been developed to analyse whether the model is structurally identifiable or otherwise. Another well-used modelling framework, which is particularly useful when the experimental data are sparsely sampled and the population variance is of interest, is mixed-effects modelling. However, established identifiability analysis techniques for ordinary differential equations are not directly applicable to such models. METHODS: In this paper, we present and apply three different methods that can be used to study structural identifiability in mixed effects models. The first method, called the repeated measurement approach, is based on applying a set of previously established statistical theorems. The second method, called the augmented system approach, is based on augmenting the mixed-effects model to an extended state-space form. The third method, called the Laplace transform mixed-effects extension, is based on considering the moment invariants of the systems transfer function as functions of random variables. RESULTS: To illustrate, compare and contrast the application of the three methods, they are applied to a set of mixed-effects models. CONCLUSIONS: Three structural identifiability analysis methods applicable to mixed-effects models have been presented in this paper. As method development of structural identifiability techniques for mixed-effects models has been given very little attention, despite mixed-effects models being widely used, the methods presented in this paper provides a way of handling structural identifiability in mixed effects models previously not possible. PMID- 27181651 TI - Revealing the role of oxidation state in interaction between nitro/amino-derived particulate matter and blood proteins. AB - Surface oxidation states of ultrafine particulate matter can influence the proinflammatory responses and reactive oxygen species levels in tissue. Surface active species of vehicle-emission soot can serve as electron transfer-mediators in mitochondrion. Revealing the role of surface oxidation state in particles proteins interaction will promote the understanding on metabolism and toxicity. Here, the surface oxidation state was modeled by nitro/amino ligands on nanoparticles, the interaction with blood proteins were evaluated by capillary electrophoresis quantitatively. The nitro shown larger affinity than amino. On the other hand, the affinity to hemoglobin is 10(3) times larger than that to BSA. Further, molecular docking indicated the difference of binding intensity were mainly determined by hydrophobic forces and hydrogen bonds. These will deepen the quantitative understanding of protein-nanoparticles interaction from the perspective of surface chemical state. PMID- 27181678 TI - Nanoencapsulation of Red Ginseng Extracts Using Chitosan with Polyglutamic Acid or Fucoidan for Improving Antithrombotic Activities. AB - The potential of nanoencapsulation using bioactive coating materials for improving antithrombotic activities of red ginseng extract (RG) was examined. RG loaded chitosan (CS) nanoparticles were prepared using antithrombotic materials, polyglutamic acid (PGA) or fucoidan (Fu). Both CS-PGA (P-NPs, 360 +/- 67 nm) and CS-Fu nanoparticles (F-NPs, 440 +/- 44 nm) showed sustained ginsenoside release in an acidic environment and improved ginsenoside solubility by approximately 122.8%. Both in vitro rabbit and ex vivo rat platelet aggregation of RG (22.3 and 41.5%) were significantly (p < 0.05) decreased within P-NPs (14.4 and 30.0%) and F-NPs (12.3 and 30.3%), respectively. Although RG exhibited no effect on in vivo carrageenan-induced mouse tail thrombosis, P-NPs and F-NPs demonstrated significant effects, likely the anticoagulation activity of PGA and Fu. Moreover, in the in vivo rat arteriovenous shunt model, P-NPs (156 +/- 6.8 mg) and F-NPs (160 +/- 3.2 mg) groups showed significantly lower thrombus formation than that of RG (190 +/- 5.5 mg). Therefore, nanoencapsulation using CS, PGA, and Fu is a potential for improving the antithrombotic activity of RG. PMID- 27181679 TI - MEK2 controls the activation of MKK3/MKK6-p38 axis involved in the MDA-MB-231 breast cancer cell survival: Correlation with cyclin D1 expression. AB - The Ras-Raf-MEK-ERK1/2 signaling pathway regulates fundamental processes in malignant cells. However, the exact contributions of MEK1 and MEK2 to the development of cancer remain to be established. We studied the effects of MEK small-molecule inhibitors (PD98059 and U0126) and MEK1 and MEK2 knock-down on cell proliferation, apoptosis and MAPK activation. We showed a diminution of cell viability that was associated with a downregulation of cyclin D1 expression and an increase of apoptosis marker in MEK2 silenced cells; by contrast, a slight increase of cell survival was observed in the absence of MEK1 that correlated with an augment of cyclin D1 expression. These data indicate that MEK2 but not MEK1 is essential for MDA-MB-231 cell survival. Importantly, the role of MEK2 in cell survival appeared independent on ERK1/2 phosphorylation since its absence did not alter the level of activated ERK1/2. Indeed, we have reported an unrevealed link between MEK2 and MKK3/MKK6-p38 MAPK axis where MEK2 was essential for the phosphorylation of MKK3/MKK6 and p38 MAPK that directly impacted on cyclin D1 expression. Importantly, the MEK1 inhibitor PD98059, like MEK1 silencing, induced an augment of cyclin D1 expression that correlated with an increase of MDA-MB-231 cell proliferation suggesting that MEK1 may play a regulatory role in these cells. In sum, the crucial role of MEK2 in MDA-MB-231 cell viability and the unknown relationship between MEK2 and MKK3/MKK6-p38 axis here revealed may open new therapeutic strategies for aggressive breast cancer. PMID- 27181680 TI - High therapeutic efficacy of Cathelicidin-WA against postweaning diarrhea via inhibiting inflammation and enhancing epithelial barrier in the intestine. AB - Diarrhea is a leading cause of death among young mammals, especially during weaning. Here, we investigated the effects of Cathelicidin-WA (CWA) on diarrhea, intestinal morphology, inflammatory responses, epithelial barrier and microbiota in the intestine of young mammals during weaning. Piglets with clinical diarrhea were selected and treated with saline (control), CWA or enrofloxacin (Enro) for 4 days. Both CWA and Enro effectively attenuated diarrhea. Compared with the control, CWA decreased IL-6, IL-8 and IL-22 levels and reduced neutrophil infiltration into the jejunum. CWA inhibited inflammation by down-regulating the TLR4-, MyD88- and NF-kappaB-dependent pathways. Additionally, CWA improved intestinal morphology by increasing villus and microvillus heights and enhancing intestinal barrier function by increasing tight junction (TJ) protein expression and augmenting wound-healing ability in intestinal epithelial cells. CWA also improved microbiota composition and increased short-chain fatty acid (SCFA) levels in feces. By contrast, Enro not only disrupted the intestinal barrier but also negatively affected microbiota composition and SCFA levels in the intestine. In conclusion, CWA effectively attenuated inflammation, enhanced intestinal barrier function, and improved microbiota composition in the intestines of weaned piglets. These results suggest that CWA could be an effective and safe therapy for diarrhea or other intestinal diseases in young mammals. PMID- 27181681 TI - Mutations in the Histone Modifier PRDM6 Are Associated with Isolated Nonsyndromic Patent Ductus Arteriosus. AB - Nonsyndromic patent ductus arteriosus (PDA) is a common congenital heart defect (CHD) with both inherited and acquired causes, but the disease mechanisms have remained elusive. Using combined genome-wide linkage analysis and whole-exome sequencing (WES), we identified independent mutations in PRDM6, which encodes a nuclear protein that is specific to vascular smooth muscle cells (VSMC), has histone methyl transferase activities, and acts as a transcriptional suppressor of contractile proteins. In vitro assays showed that the mutations cause loss of function either by intracellular redistribution of the protein and/or by alteration of its methyltransferase activities. Wild-type embryonic ductus arteriosus (DA) exhibited high levels of PRDM6, which rapidly declined postnatally as the number of VSMCs necessary for ductus contraction increased. This dynamic change suggests that PRDM6 plays a key role in maintaining VSMCs in an undifferentiated stage in order to promote their proliferation and that its loss of activity results in premature differentiation and impaired remodeling of the DA. Our findings identify PRDM6 mutations as underlying genetic causes of nonsyndromic isolated PDA in humans and implicates the wild-type protein in epigenetic regulation of ductus remodeling. PMID- 27181683 TI - Loss of MAFB Function in Humans and Mice Causes Duane Syndrome, Aberrant Extraocular Muscle Innervation, and Inner-Ear Defects. AB - Duane retraction syndrome (DRS) is a congenital eye-movement disorder defined by limited outward gaze and retraction of the eye on attempted inward gaze. Here, we report on three heterozygous loss-of-function MAFB mutations causing DRS and a dominant-negative MAFB mutation causing DRS and deafness. Using genotype phenotype correlations in humans and Mafb-knockout mice, we propose a threshold model for variable loss of MAFB function. Postmortem studies of DRS have reported abducens nerve hypoplasia and aberrant innervation of the lateral rectus muscle by the oculomotor nerve. Our studies in mice now confirm this human DRS pathology. Moreover, we demonstrate that selectively disrupting abducens nerve development is sufficient to cause secondary innervation of the lateral rectus muscle by aberrant oculomotor nerve branches, which form at developmental decision regions close to target extraocular muscles. Thus, we present evidence that the primary cause of DRS is failure of the abducens nerve to fully innervate the lateral rectus muscle in early development. PMID- 27181685 TI - Efficacy of Combined Ultrasound-and-Microbubbles-Mediated Diclofenac Gel Delivery to Enhance Transdermal Permeation in Adjuvant-Induced Rheumatoid Arthritis in the Rat. AB - A previous study that investigated the effect of ultrasound (US) on the transdermal permeation of the non-steroidal anti-inflammatory drug diclofenac found that therapeutic US can increase circulation in an inflamed joint and decrease arthritic pain. Transdermal drug delivery has recently been demonstrated by US combined with microbubbles (MB) contrast agent (henceforth referred to as "US-MB"). The present study evaluated the efficacy of US-MB-mediated diclofenac delivery for treating adjuvant-induced rheumatoid arthritis (RA) in rats. RA was induced by injecting 100 MUL of complete Freund's adjuvant into the ankle joint of male Sprague-Dawley rats (250-300 g) that were randomly divided into five treatment groups: (i) carbopol gel alone (the control [group C]), (ii) diclofenac carbopol gel (group D), (iii) US plus carbopol gel (group U), (iv) US plus diclofenac-carbopol gel (group DU) and (v) US-MB plus diclofenac-carbopol gel (group DUB). The ankle width was measured over 10 d using high-frequency (40-MHz) US B-mode and color Doppler-mode imaging, covering the period before and after treatment. Longitudinal US images of the induced RA showed synovitis and neovascularity. Only a small amount of neovascularity was observed after treatment. The recovery rate on day 10 was significantly higher in group DUB (97.7% +/- 2.7%, mean +/- standard deviation [SD]) than in groups C (1.0% +/- 2.7%), D (37.5% +/- 4.6%), U (75.5% +/- 4.2%) and DU (87.3% +/- 5.2%) (p < 0.05). The results obtained indicate that combining US and MB can increase the skin permeability and thereby enhance the delivery of diclofenac sodium gel and thereby inhibit inflammation of the tissues surrounding the arthritic ankle. Color Doppler-mode imaging revealed that US-MB treatment induced a rapid reduction in synovial neoangiogenesis in the arthritic area. PMID- 27181684 TI - Performance of ACMG-AMP Variant-Interpretation Guidelines among Nine Laboratories in the Clinical Sequencing Exploratory Research Consortium. AB - Evaluating the pathogenicity of a variant is challenging given the plethora of types of genetic evidence that laboratories consider. Deciding how to weigh each type of evidence is difficult, and standards have been needed. In 2015, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) published guidelines for the assessment of variants in genes associated with Mendelian diseases. Nine molecular diagnostic laboratories involved in the Clinical Sequencing Exploratory Research (CSER) consortium piloted these guidelines on 99 variants spanning all categories (pathogenic, likely pathogenic, uncertain significance, likely benign, and benign). Nine variants were distributed to all laboratories, and the remaining 90 were evaluated by three laboratories. The laboratories classified each variant by using both the laboratory's own method and the ACMG-AMP criteria. The agreement between the two methods used within laboratories was high (K-alpha = 0.91) with 79% concordance. However, there was only 34% concordance for either classification system across laboratories. After consensus discussions and detailed review of the ACMG-AMP criteria, concordance increased to 71%. Causes of initial discordance in ACMG-AMP classifications were identified, and recommendations on clarification and increased specification of the ACMG-AMP criteria were made. In summary, although an initial pilot of the ACMG-AMP guidelines did not lead to increased concordance in variant interpretation, comparing variant interpretations to identify differences and having a common framework to facilitate resolution of those differences were beneficial for improving agreement, allowing iterative movement toward increased reporting consistency for variants in genes associated with monogenic disease. PMID- 27181686 TI - Toward Deep Brain Monitoring with Superficial EEG Sensors Plus Neuromodulatory Focused Ultrasound. AB - Noninvasive recordings of electrophysiological activity have limited anatomic specificity and depth. We hypothesized that spatially tagging a small volume of brain with a unique electroencephalography (EEG) signal induced by pulsed focused ultrasound could overcome those limitations. As a first step toward testing this hypothesis, we applied transcranial ultrasound (2 MHz, 200-ms pulses applied at 1050 Hz for 1 s at a spatial peak temporal average intensity of 1.4 W/cm(2)) to the brains of anesthetized rats while simultaneously recording EEG signals. We observed a significant 1050-Hz electrophysiological signal only when ultrasound was applied to a living brain. Moreover, amplitude demodulation of the EEG signal at 1050 Hz yielded measurement of gamma band (>30 Hz) brain activity consistent with direct measurements of that activity. These results represent preliminary support for use of pulsed focused ultrasound as a spatial tagging mechanism for non-invasive EEG-based mapping of deep brain activity with high spatial resolution. PMID- 27181687 TI - Real-Time Elastography and Contrast-Enhanced Ultrasonography in the Evaluation of Testicular Masses: A Comparative Prospective Study. AB - This study investigates the usefulness of contrast-enhanced ultrasound (CEUS) and real-time elastography (RTE) for the characterization of testicular masses by comparing pre-operative ultrasound findings with post-operative histology. Sixty seven patients with 68 sonographically detected testicular masses underwent B mode, color-coded Doppler sonography (CCDS), CEUS and RTE according to defined criteria. For RTE, elasticity score (ES), difference of elasticity score (D-ES), strain ratio (SR) and size quotient (Qsize) were evaluated. Histopathologically, 54/68 testicular lesions were neoplastic (47 malignant, 7 benign). Descriptive statistics revealed the following results (neoplastic vs. non-neoplastic) for sensitivity, specificity, positive predictive value, negative predictive value and accuracy, respectively: B-mode, 100%, 43%, 87%, 100%, 88%; CCDS 81%, 86%, 96%, 55%, 82%; CEUS 93%, 85%, 96%, 73%, 91%; ES 98%, 25%, 85%, 75%, 85%; D-ES 98%, 50%, 90%, 83%, 89%; SR 90%, 45%, 86%, 56%, 81%; and Qsize 57%, 83%, 94%, 28%, 61%. B-mode with CCDS remains the standard for assessing testicular masses. In characterization of testicular lesions, CEUS clearly outperformed all other modalities. Our study does not support the routine use of RTE in testicular ultrasonography because of its low specificity. PMID- 27181688 TI - Comparative Study of Three Regimens of Bowel Preparation Before Transabdominal Ultrasonography of the Colon. AB - The objective of the study was to compare the efficacy of three bowel preparation regimens for transabdominal colon ultrasonography. A total of 192 consecutive patients were given one of three regimens (senna, magnesium sulfate or polyethylene glycol electrolyte powder) before ultrasonographic examinations. The cleaning grade (I = emptying; II = filled or filled + empty; III = I or II with some retention; and IV = retention [grades I and II were termed "qualified"]) and cleaning range (A = all seven colon sections were qualified; B = four to six sections were qualified; C = three or less sections were qualified) were evaluated retrospectively. Senna was found more effective than polyethylene glycol in terms of cleaning grade (p < 0.001), qualified rate (p < 0.001) and cleaning range (p = 0.003). Senna was better than magnesium sulfate in cleaning grade (p < 0.001). Our results suggest that senna seems to be the preferred regimen for bowel preparation before transabdominal colonic ultrasonography. PMID- 27181689 TI - Frequency Analysis of the Photoacoustic Signal Generated by Coronary Atherosclerotic Plaque. AB - The identification of unstable atherosclerotic plaques in the coronary arteries is emerging as an important tool for guiding percutaneous coronary interventions and may enable preventive treatment of such plaques in the future. Assessment of plaque stability requires imaging of both structure and composition. Spectroscopic photoacoustic (sPA) imaging can visualize atherosclerotic plaque composition on the basis of the optical absorption contrast. It is an established fact that the frequency content of the photoacoustic (PA) signal is correlated with structural tissue properties. As PA signals can be weak, it is important to match the transducer bandwidth to the signal frequency content for in vivo imaging. In this ex vivo study on human coronary arteries, we combined sPA imaging and analysis of frequency content of the PA signals. Using a broadband transducer (-3-dB one-way bandwidth of 10-35 MHz) and a 1-mm needle hydrophone (calibrated for 1-20 MHz), we covered a large frequency range of 1-35 MHz for receiving the PA signals. Spectroscopic PA imaging was performed at wavelengths ranging from 1125 to 1275 nm with a step of 2 nm, allowing discrimination between plaque lipids and adventitial tissue. Under sPA imaging guidance, the frequency content of the PA signals from the plaque lipids was quantified. Our data indicate that more than 80% of the PA energy of the coronary plaque lipids lies in the frequency band below 8 MHz. This frequency information can guide the choice of the transducer element used for PA catheter fabrication. PMID- 27181690 TI - Sex- and Maturity-Related Differences in Cortical Bone at the Distal Radius and Midshaft Tibia Evaluated by Quantitative Ultrasonography. AB - Boys usually have higher values of bone mineral density measured by dual-energy X ray absorptiometry than girls, but contradictorily also have a greater incidence of fractures during growth. The purpose of this study was to investigate sex- and maturity-related differences in bone speed of sound (SoS) at the radius and tibia in a sample of 625 healthy children aged 10-14 y and to analyze the contributions of physical activity (PA) to possible dissimilarities. Radial and tibial SoS was evaluated by quantitative ultrasound, maturity was estimated as the years of distance from the peak height velocity age, and PA was assessed by accelerometry. Comparisons between sexes and maturity groups (low: below average [<-2.5 y], high: average or above [>=-2.5 y]) were made by two-sample t-tests with unequal variances. Girls in the high-maturity group had higher SoS at the radius and tibia compared with girls in the low-maturity group (p < 0.001). There were no SoS differences at the radius or tibia between the high- and low-maturity groups in boys. Within high-maturity children, girls had higher SoS than boys at the radius and tibia (p < 0.001). There were no differences at the radius and tibia between girls and boys with low maturity. The results were not modified after controlling for PA. Regardless of PA, the results provide insight into sex- and maturity-related differences in bone SoS at the distal radius and midshaft tibia from maturity less than 2.5 y from the peak height velocity age, with boys having lower SoS. PMID- 27181691 TI - Confined SnO2 quantum-dot clusters in graphene sheets as high-performance anodes for lithium-ion batteries. AB - Construction of metal oxide nanoparticles as anodes is of special interest for next-generation lithium-ion batteries. The main challenge lies in their rapid capacity fading caused by the structural degradation and instability of solid electrolyte interphase (SEI) layer during charge/discharge process. Herein, we address these problems by constructing a novel-structured SnO2-based anode. The novel structure consists of mesoporous clusters of SnO2 quantum dots (SnO2 QDs), which are wrapped with reduced graphene oxide (RGO) sheets. The mesopores inside the clusters provide enough room for the expansion and contraction of SnO2 QDs during charge/discharge process while the integral structure of the clusters can be maintained. The wrapping RGO sheets act as electrolyte barrier and conductive reinforcement. When used as an anode, the resultant composite (MQDC-SnO2/RGO) shows an extremely high reversible capacity of 924 mAh g(-1) after 200 cycles at 100 mA g(-1), superior capacity retention (96%), and outstanding rate performance (505 mAh g(-1) after 1000 cycles at 1000 mA g(-1)). Importantly, the materials can be easily scaled up under mild conditions. Our findings pave a new way for the development of metal oxide towards enhanced lithium storage performance. PMID- 27181693 TI - Sandwich phosphate complexes of macrocyclic tris(urea) ligands and their rotation around the anion. AB - Four heteroditopic macrocyclic ligands incorporating both anion coordination sites (tris-urea units) and a cation binding fragment (polyether) were designed for possible application in molecular devices. Sandwich-type phosphate complexes were formed, which display a reversible rotation around the anion upon protonation/deprotonation of phosphate and binding of the cation (Emim(+)). PMID- 27181692 TI - A method for controlling the synthesis of stable twisted two-dimensional conjugated molecules. AB - Thermodynamic stabilization (pi-electron delocalization through effective conjugation) and kinetic stabilization (blocking the most-reactive sites) are important considerations when designing stable polycyclic aromatic hydrocarbons displaying tunable optoelectronic properties. Here, we demonstrate an efficient method for preparing a series of stable two-dimensional (2D) twisted dibenzoterrylene-acenes. We investigated their electronic structures and geometries in the ground state through various experiments assisted by calculations using density functional theory. We find that the length of the acene has a clear effect on the photophysical, electrochemical, and magnetic properties. These molecules exhibit tunable ground-state structures, in which a stable open-shell quintet tetraradical can be transferred to triplet diradicals. Such compounds are promising candidates for use in nonlinear optics, field effect transistors and organic spintronics; furthermore, they may enable broader applications of 2D small organic molecules in high-performance electronic and optical devices. PMID- 27181682 TI - Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine. AB - Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence based development of best practices in genomic medicine. PMID- 27181694 TI - Donor/acceptor chromophores-decorated triazolyl unnatural nucleosides: synthesis, photophysical properties and study of interaction with BSA. AB - Much effort has been put forth to develop unnatural, stable, hydrophobic base pairs with orthogonal recognition properties and study their effect on DNA duplex stabilisation. Our continuous efforts on the design of fluorescent unnatural biomolecular building blocks lead us to the synthesis of some triazolyl donor/acceptor unnatural nucleosides via an azide-alkyne 1,3-dipolar cycloaddition reaction as a key step, which we want to report herein. We have studied their photophysical properties and found interesting solvatochromic fluorescence for two of the nucleosides. Photophysical interactions among two donor-acceptor beta-nucleosides as well as a pair of alpha/beta-nucleosides have also been evaluated. Furthermore, we have exploited one of the fluorescent nucleosides in studying its interaction with BSA with the help of UV-visible and steady state fluorescence techniques. Our design concept is based on the hypothesis that a pair of such donor/acceptor nucleosides might be involved in pi stacking as well as in photophysical interactions, leading to stabilization of the DNA duplex if such nucleosides can be incorporated into short oligonucleotide sequences. Therefore, the designed bases may find application in biophysical studies in the context of DNA. PMID- 27181695 TI - Structural-functional lung imaging using a combined CT-EIT and a Discrete Cosine Transformation reconstruction method. AB - Lung EIT is a functional imaging method that utilizes electrical currents to reconstruct images of conductivity changes inside the thorax. This technique is radiation free and applicable at the bedside, but lacks of spatial resolution compared to morphological imaging methods such as X-ray computed tomography (CT). In this article we describe an approach for EIT image reconstruction using morphologic information obtained from other structural imaging modalities. This leads to recon- structed images of lung ventilation that can easily be superimposed with structural CT or MRI images, which facilitates image interpretation. The approach is based on a Discrete Cosine Transformation (DCT) of an image of the considered transversal thorax slice. The use of DCT enables reduction of the dimensionality of the reconstruction and ensures that only conductivity changes of the lungs are reconstructed and displayed. The DCT based approach is well suited to fuse morphological image information with functional lung imaging at low computational costs. Results on simulated data indicate that this approach preserves the morphological structures of the lungs and avoids blurring of the solution. Images from patient measurements reveal the capabilities of the method and demonstrate benefits in possible applications. PMID- 27181696 TI - Can a dietary quality score derived from a short-form FFQ assess dietary quality in UK adult population surveys? AB - OBJECTIVE: To devise a measure of diet quality from a short-form FFQ (SFFFQ) for population surveys. To validate the SFFFQ against an extensive FFQ and a 24 h diet recall. DESIGN: Population-based cross-sectional survey. SETTING: East Leeds and Bolton in Northern England. SUBJECTS: Adults (n 1999) were randomly selected from lists of those registered with a general practitioner in the study areas, contacted by mail and asked to complete the SFFFQ. Responders were sent a longer FFQ to complete and asked if they would take part in a telephone-based 24 h diet recall. RESULTS: Results from 826 people completing the SFFFQ, 705 completing the FFQ and forty-seven completing the diet recall were included in the analyses. The dietary quality score (DQS), based on fruit, vegetable, oily fish, non-milk extrinsic sugar and fat intakes, showed significant agreement between the SFFFQ and the FFQ (kappa=0.38, P<0.001). The DQS for the SFFFQ and the diet recall did not show significant agreement (kappa=0.04, P=0.312). A number of single items on the SFFFQ predicted a 'healthy' DQS when calculated from the FFQ. The odds of having a healthy diet were increased by 27 % (95 % CI 9, 49 %, P<0.001) for an increase in fruit of 1 portion/d and decreased by 67 % (95 % CI 47, 79 %, P<0.001) for an increase in crisps of 1 portion/d. CONCLUSIONS: The SFFFQ has been shown to be an effective method of assessing diet quality. It provides an important method for determining variations in diet quality within and across different populations. PMID- 27181700 TI - Addendum. PMID- 27181699 TI - Long-term safety and efficacy of a novel once-weekly oral trelagliptin as monotherapy or in combination with an existing oral antidiabetic drug in patients with type 2 diabetes mellitus: A 52-week open-label, phase 3 study. AB - AIMS/INTRODUCTION: Trelagliptin is a novel once-weekly oral dipeptidyl peptidase 4 inhibitor for type 2 diabetes mellitus that was first approved in Japan. We evaluated long-term safety and efficacy of trelagliptin in Japanese patients with type 2 diabetes mellitus. MATERIALS AND METHODS: This was a phase 3, multicenter, open-label study to evaluate long-term safety and efficacy of trelagliptin. Patients with type 2 diabetes mellitus inadequately controlled despite diet/exercise or treatment with one of the existing oral antidiabetic drugs along with diet/exercise received trelagliptin 100 mg orally once weekly for 52 weeks as monotherapy or combination therapies. The primary end-points were the safety variables, and the secondary end-points were glycosylated hemoglobin and fasting plasma glucose. RESULTS: A total of 680 patients received the following antidiabetic therapies: trelagliptin monotherapy (n = 248), combination with a sulfonylurea (n = 158), a glinide (n = 67), an alpha-glucosidase inhibitor (n = 65), a biguanide (n = 70), or a thiazolidinedione (n = 72). During the study, 79.8% of the patients experienced at least one adverse event for monotherapy, 87.3% for combination with a sulfonylurea, 77.6% for a glinide, 81.5% for an alpha-glucosidase inhibitor, 64.3% for a biguanide, and 84.7% for a thiazolidinedione, respectively. Most of the adverse events were mild or moderate. The change in glycosylated hemoglobin from baseline at the end of the treatment period was -0.74 to -0.25% for each therapy. CONCLUSIONS: Once-weekly oral trelagliptin provides well-tolerated long-term safety and efficacy in both monotherapy and combination therapies in Japanese patients with type 2 diabetes mellitus. PMID- 27181701 TI - Giant edge state splitting at atomically precise graphene zigzag edges. AB - Zigzag edges of graphene nanostructures host localized electronic states that are predicted to be spin-polarized. However, these edge states are highly susceptible to edge roughness and interaction with a supporting substrate, complicating the study of their intrinsic electronic and magnetic structure. Here, we focus on atomically precise graphene nanoribbons whose two short zigzag edges host exactly one localized electron each. Using the tip of a scanning tunnelling microscope, the graphene nanoribbons are transferred from the metallic growth substrate onto insulating islands of NaCl in order to decouple their electronic structure from the metal. The absence of charge transfer and hybridization with the substrate is confirmed by scanning tunnelling spectroscopy, which reveals a pair of occupied/unoccupied edge states. Their large energy splitting of 1.9 eV is in accordance with ab initio many-body perturbation theory calculations and reflects the dominant role of electron-electron interactions in these localized states. PMID- 27181702 TI - Pathogenic mechanisms in Blastocystis spp. - Interpreting results from in vitro and in vivo studies. AB - Blastocystis spp. are commonly reported intestinal protists but whose clinical significance remains controversial. Infections have ranged from asymptomatic carriage to non-specific gastrointestinal symptoms and have also been linked to irritable bowel syndrome and urticaria in some patient populations. In vitro studies showed that both parasite and parasite lysates have damaging effects on intestinal epithelial cells causing apoptosis and degradation of tight junction proteins occludin and ZO1, resulting in increased intestinal permeability. Adhesion of trophic forms to the intestinal epithelium and release of cysteine proteases appear to be the major triggers leading to pathogenesis. Two putative virulence factors identified are cysteine proteases legumain and cathepsin B. Blastocystis spp. also have immuno-modulatory effects including degradation of IgA, inhibition of iNOS and upregulation of proinflammatory cytokines, IL8 and GM CSF in intestinal epithelial cells and IL1beta, IL6 and TNFalpha in murine macrophages. Blastocystis spp. have also been reported to dampen response to LPS in intestinal epithelial cells and monocytes. Studies in rodent models and naturally infected pigs have shown that the parasite localizes to the lumen and mucosal surface of the large intestine mostly in the caecum and colon. The parasite has been found to cause mucosal sloughing, increase in goblet cell mucin, increased intestinal permeability and to induce a pro-inflammatory cytokine response with upregulation of TNFalpha, IFNgamma and IL12. In this review, we summarize findings from in vitro and in vivo studies that demonstrate pathogenic potential but also show considerable inter and intra subtype variation, which provides a plausible explanation on the conflicting reports on clinical significance. PMID- 27181703 TI - Azadipyrromethenes: from traditional dye chemistry to leading edge applications. AB - Azadipyrromethenes were first described over 70 years ago as blue pigments, but now are rapidly emerging as a compound class with highly desirable near infrared photophysical properties. Since the turn of the century several routes to azadipyrromethenes have been developed and numerous post-synthesis derivatizations have allowed for their exploitation in both biological and material sciences. The relative ease of access to specifically designed derivatives is now allowing their use in multiple technological formats from real time fluorescence imaging, to solar energy materials, to optoelectronic devices and many more. In this review we have highlighted the synthetic component of this story as it is the ability to generate the designer azadipyrromethene that opens the door to exciting applications. PMID- 27181704 TI - The association between openness and physiological responses to recurrent social stress. AB - The association between openness (assessed by shortened Chinese version of NEO Five-Factor Inventory, NEOFFI) and physiological reactivity to, and recovery from, social stress (a video-recorded, timed public speaking task with evaluators present in the room), and physiological adaptation to repeated social stress was examined in the present study. Subjective and physiological data were collected from 70 college students across five laboratory stages: baseline, stress exposure period 1, post-stress period 1, stress exposure period 2, and post-stress period 2. Results indicated that higher openness was associated with lesser heart rate (HR) reactivity to the first and second stress exposure, and lesser systolic blood pressure (SBP) reactivity to the second stress exposure. Higher openness was associated with higher resting respiratory sinus arrhythmia (RSA), lesser RSA withdrawals to the first stress exposure, and more complete RSA recovery after the first stress exposure. Moreover, higher openness was associated with pronounced systolic and diastolic blood pressure (SBP, DBP) adaptation with greater decreases in SBP and DBP reactivity across the two successive stress exposures. These findings might shed light on the biological basis linking openness to health. PMID- 27181705 TI - The global burden of pulmonary hypertension in sickle cell disease: a systematic review and meta-analysis. AB - Elevated tricuspid regurgitant jet velocity (TRJV) is a surrogate measure of pulmonary hypertension (PH) in persons with sickle cell disease (SCD). We sought to estimate the burden of PH in people living with sickle cell disease based on TRJV. From 2000 to 2015, we searched electronic databases for eligible publications and included 29 studies (n = 5358 persons). We used random effects modeling to determine the pooled estimate of elevated TRJV. The overall pooled prevalence of elevated TRJV was 23.5 %(95 % CI 19.5-27.4) in persons with SCD. The pooled prevalence of elevated TRJV in children and adults with SCD was 20.7 % (95 % CI 15.7--25.6) and 24.4 % (95 % CI 18.4-30.4), respectively. TRJV is prevalent among adults and children with SCD. Our finding support international recommendations that call for screening for PH in SCD patients. PMID- 27181706 TI - Association of ADIPOQ variants with type 2 diabetes mellitus susceptibility in ethnic Han Chinese from northeast China. AB - AIMS/INTRODUCTION: To investigate the association between two single nucleotide polymorphisms (SNPs; rs3774261 and rs822393) in the ADIPOQ gene and type 2 diabetes mellitus in Han Chinese from northeast China. MATERIALS AND METHODS: The present study comprised 993 type 2 diabetes mellitus patients and 966 unrelated controls from northeastern China. Two SNPs were sequenced using SNPscan. The distribution of genotype frequencies of the two SNPs in ADIPOQ between cases and controls, and in subgroups stratified based on body mass index, were compared using logistic regression analysis. Linear regression was used to analyze the association between each SNP and clinical indicators. RESULTS: The GG genotype of rs3774261 increased the risk of type 2 diabetes mellitus compared with the AA genotype in participants with a body mass index <24 (P = 0.021; odds ratio 1.636, 95% CI 1.708-2.484). Rs822393 was correlated with glycosylated hemoglobin (P = 0.043) in controls. Rs3774261 had an association with diastolic blood pressure (P = 0.017) in controls, and in controls with a body mass index <24; rs3774261 also had an association with both systolic blood pressure (P = 0.025) and diastolic blood pressure (P = 0.043). CONCLUSIONS: The present results confirm the association between ADIPOQ variants and type 2 diabetes mellitus in northeastern China. However, additional larger replication studies are required to validate these findings. PMID- 27181707 TI - Can we improve clinical outcomes in patients with pneumonia treated with antibiotics in the intensive care unit? AB - INTRODUCTION: Pneumonia in the intensive care unit (ICU) is associated with high morbidity, mortality and healthcare costs. However, treatment outcomes with conventional intravenous (IV) antibiotics remain suboptimal, and there is an urgent need for improved therapy options. AREAS COVERED: We review how clinical outcomes in patients with pneumonia treated in the ICU could be improved; we discuss the importance of choosing appropriate outcome measures in clinical trials, highlight the current suboptimal outcomes in patients with pneumonia, and outline potential solutions. We have included key studies and papers based on our clinical expertise, therefore a systematic literature review was not conducted. Expert commentary: Reasons for poor outcomes in patients with nosocomial pneumonia in the ICU include inappropriate initial therapy, increasing bacterial resistance and the complexities of IV dosing in critically ill patients. Robust clinical trial endpoints are needed to enable an accurate assessment of the success of new treatment approaches, but progress in this field has been slow. In addition, only very few new antimicrobials are currently in development for nosocomial pneumonia; two potential alternative solutions to improve outcomes could therefore include the optimization of pharmacokinetic/pharmacodynamics (PK/PD) and dosing of existing therapies, and the refinement of antimicrobial delivery by inhalation. PMID- 27181708 TI - Re-examining the high-density lipoprotein hypothesis. PMID- 27181709 TI - On-Tissue Derivatization via Electrospray Deposition for Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging of Endogenous Fatty Acids in Rat Brain Tissues. AB - Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) is used for the multiplex detection and characterization of diverse analytes over a wide mass range directly from tissues. However, analyte coverage with MALDI MSI is typically limited to the more abundant compounds, which have m/z values that are distinct from MALDI matrix-related ions. On-tissue analyte derivatization addresses these issues by selectively tagging functional groups specific to a class of analytes, while simultaneously changing their molecular masses and improving their desorption and ionization efficiency. We evaluated electrospray deposition of liquid-phase derivatization agents as a means of on tissue analyte derivatization using 2-picolylamine; we were able to detect a range of endogenous fatty acids with MALDI MSI. When compared with airbrush application, electrospray led to a 3-fold improvement in detection limits and decreased analyte delocalization. Six fatty acids were detected and visualized from rat cerebrum tissue using a MALDI MSI instrument operating in positive mode. MALDI MSI of the hippocampal area allowed targeted fatty acid analysis of the dentate gyrus granule cell layer and the CA1 pyramidal layer with a 20-MUm pixel width, without degrading the localization of other lipids during liquid-phase analyte derivatization. PMID- 27181710 TI - Topoisomerase I in Human Disease Pathogenesis and Treatments. AB - Mammalian topoisomerase 1 (TOP1) is an essential enzyme for normal development. TOP1 relaxes supercoiled DNA to remove helical constraints that can otherwise hinder DNA replication and transcription and thus block cell growth. Unfortunately, this exact activity can covalently trap TOP1 on the DNA that could lead to cell death or mutagenesis, a precursor for tumorigenesis. It is therefore important for cells to find a proper balance between the utilization of the TOP1 catalytic activity to maintain DNA topology and the risk of accumulating the toxic DNA damages due to TOP1 trapping that prevents normal cell growth. In an apparent contradiction to the negative attribute of the TOP1 activity to genome stability, the detrimental effect of the TOP1-induced DNA lesions on cell survival has made this enzyme a prime target for cancer therapies to kill fast growing cancer cells. In addition, cumulative evidence supports a direct role of TOP1 in promoting transcriptional progression independent of its topoisomerase activity. The involvement of TOP1 in transcriptional regulation has recently become a focus in developing potential new treatments for a subtype of autism spectrum disorders. Clearly, the impact of TOP1 on human health is multifold. In this review, we will summarize our current understandings on how TOP1 contributes to human diseases and how its activity is targeted for disease treatments. PMID- 27181712 TI - Dorsal transcription factor is involved in regulating expression of crustin genes during white spot syndrome virus infection. AB - Nuclear factor-kappa B (NF-kappaB) pathways play important roles in innate immune responses. In this study, we identified a dorsal homolog (MrDorsal) from freshwater prawn Macrobrachium rosenbergii. The full-length cDNA of MrDorsal comprised 2533 bp with an open reading frame of 1986 bp, which encoded a peptide of 661 amino acid residues. Amino acid sequence analysis showed that MrDorsal contains a Rel homolog domain and an IPT/TIG (i.e., Ig-like, plexin, and transcription factors) domain. The signature sequence of dorsal protein FRYMCEG existed in the deduced amino acid sequence. Sequence analysis showed that MrDorsal shared high similarities with Dorsal from invertebrate species. MrDorsal was abundant in the hemocytes and gills of healthy prawns but minute levels were detected in other tissues. The expression of MrDorsal was significantly upregulated 48 h after the white spot syndrome virus (WSSV-) challenge. Knockdown of MrDorsal using double-stranded RNA could suppress the transcription of crustin genes (MrCrustin2 and MrCrustin4) in gills of prawns after 48 h of the WSSV challenge. Results indicated that MrDorsal was involved to regulate the expression of crustin genes and it might play potential important roles during WSSV infection. PMID- 27181713 TI - Identification and functional analysis of interferon regulatory factor 3 in Lateolabrax maculatus. AB - The interferon (IFN) regulatory factor 3 (IRF3) is a member of the IFN regulatory transcription factor family, which binds to the IFN-stimulated response element (ISRE) within the promoter of IFN genes and IFN-stimulated genes. In this study, the IRF3 cDNA of sea perch Lateolabrax maculatus (SpIRF3) was identified, which contained 1781 bp with an open reading frame of 1398 bp that coded a 465 amino acid protein. The SpIRF3 protein shared conserved characterizations with its homologues and displayed the conserved DNA-binding domain, IRF association domain, serine-rich C-terminal domain, and tryptophan residue cluster. Phylogenetic analysis illustrated that SpIRF3 belonged to the IRF3 subfamily. Subcellular localization analysis showed that SpIRF3 mainly resided in the cytoplasm without stimuli but translocated into nuclei in the presence of poly I:C. Real-time PCR data indicated that SpIRF3 was transcriptionally up-regulated by poly I:C stimulation in various organs. Moreover, reporter assay revealed that SpIRF3 functioned as a modulator in triggering the IFN response by inducing the activity of IFN and ISRE-containing promoter. These data revealed that SpIRF3 was a potential molecule in the IFN immune defense system against viral infection. PMID- 27181714 TI - Effects of ethanol extract of propolis on histopathological changes and anti oxidant defense of kidney in a rat model for type 1 diabetes mellitus. AB - AIMS/INTRODUCTION: Oxidative stress has a key role in the pathogenesis of diabetes. Propolis and its constituents have a wide range of medicinal properties against oxidative stress. In the present study, we evaluated the anti-oxidant effects of ethanolic extracts of propolis on kidneys in diabetes mellitus rats. MATERIALS AND METHODS: A total of 40 male Wistar rats were randomly divided into the following five groups: control, diabetes mellitus, diabetes mellitus with vehicle treatment, diabetes mellitus with propolis treatment (100 mg/kg) and diabetes mellitus with propolis treatment (200 mg/kg). Diabetes mellitus in rats was induced by intraperitoneal injection of streptozotocin (60 mg/kg). Diabetic groups were treated with vehicle or ethanolic extracts of Iranian propolis for 6 weeks. Serum concentration of malondialdehyde, superoxide dismutase and glutathione peroxidase were measured. RESULTS: The results showed that Iranian propolis significantly inhibited bodyweight loss in diabetes mellitus rats. The propolis extracts significantly reduced serum glucose levels and kidney weight in diabetes mellitus rats (P < 0.001). Furthermore, propolis extracts significantly reduced the malondialdehyde content, and increased the activity of superoxide dismutase and glutathione peroxidase (P < 0.001) along with the total anti oxidant activity in the kidney tissue of diabetes mellitus rats. In the kidneys of the diabetes mellitus and vehicle group, the glomerular basement membrane thickness and glomerular area were significantly increased. Treatment of diabetes mellitus rats with the propolis extract significantly reduced the glomerular basement membrane thickness and glomerular area. CONCLUSIONS: The present study results showed that the Iranian propolis extract could enhance the anti-oxidant levels and histopathological changes in the kidneys of rats. The final results showed that most of the favorable effects of propolis are mediated by a reduction of blood glucose levels in diabetic animals. PMID- 27181711 TI - Associations between whole peripheral blood fatty acids and DNA methylation in humans. AB - Fatty acids (FA) modify DNA methylation in vitro, but limited information is available on whether corresponding associations exist in vivo and reflect any short-term effect of the diet. Associations between global DNA methylation and FAs were sought in blood from lactating infants (LI; n = 49) and adult males (AMM; n = 12) equally distributed across the three conventional BMI classes. AMM provided multiple samples at 2-hour intervals during 8 hours after either a single Western diet-representative meal (post-prandial samples) or no meal (fasting samples). Lipid/glucose profile, HDAC4 promoter and PDK4 5'UTR methylation were determined in AMM. Multiple regression analysis revealed that global (in LI) and both global and PDK4-specific DNA methylation (in AMM) were positively associated with eicosapentaenoic and arachidonic acid. HDAC4 methylation was inversely associated with arachidonic acid post-prandially in AMM. Global DNA methylation did not show any defined within-day pattern that would suggest a short-term response to the diet. Nonetheless, global DNA methylation was higher in normal weight subjects both post-prandially and in fasting and coincided with higher polyunsaturated relative to monounsaturated and saturated FAs. We show for the first time strong associations of DNA methylation with specific FAs in two human cohorts of distinct age, diet and postnatal development stage. PMID- 27181716 TI - Bioequivalence and in vitro antimicrobial activity between generic and brand-name levofloxacin. AB - Generic agents play a crucial role in reducing the cost of medical care in many countries. However, the therapeutic equivalence remains a great concern. Our study aims to assess the in vitro antimicrobial activity and bioequivalence between generic and brand-name levofloxacin. Enantiomeric purity test, dissolution test, and in vitro antimicrobial susceptibility against seven clinically important pathogens by the agar dilution method were employed to assess the similarity between four generic products and brand-name levofloxacin (Daiichi Sankyo). All the generic and brand-name levofloxacin passed enantiomeric purity test. The results of dissolution tests were not similar among the generic products and the brand-name levofloxacin. Compared with the generic products, the brand-name levofloxacin had the smallest mean variations (-25% to 13%) with reference standard (United States Pharmacopeia levofloxacin Reference Standards). Variations were observed particularly in dissolution profiles and in vitro activity between generic products and brand-name levofloxacin. PMID- 27181715 TI - HIV Infection Rates and Risk Behavior among Young Men undergoing community-based Testing in San Diego. AB - Approximately 80% of new HIV infections in the United States occur in men. Four out of five men diagnosed with HIV infection are men who have sex with men (MSM), with an increasing proportion of young MSM (i.e. <=24 years of age). We performed a retrospective analysis 11,873 cisgender men participating in a community based HIV screening program in San Diego between 2008 and 2014 to characterize the HIV prevalence and sexual risk behaviors among young men. In young heterosexual men HIV prevalence was lower compared to heterosexual men between 25 and 49 years of age (0.3% vs. 1.4%, p = 0.043). Among young MSM, HIV prevalence was 5.5%, per test positivity rate 3.6%, and HIV incidence 3.4 per 100 person years (95% CI 2.2 5.4). Per test positivity rate (p = 0.008) and incidence (p < 0.001) were significantly higher among young MSM than among MSM above 24-years of age. Young MSM diagnosed with HIV infection reported significantly more serodiscordant condomless anal intercourse, bacterial sexually transmitted infections, and higher rates of methamphetamine and gamma hydroxybutyrate use when compared to young MSM who tested negative. In conclusion, young MSM are particularly vulnerable to HIV infection and may represent ideal candidates for targeted prevention interventions that increase testing uptake and/or decrease the risk of acquiring HIV infection. PMID- 27181718 TI - [Effects of microRNA-494 on the fiber type-specific skeletal myogenesis in human induced pluripotent stem cells]. PMID- 27181717 TI - Androgen deprivation therapy is associated with diabetes: Evidence from meta analysis. AB - AIMS/INTRODUCTION: There is still no obvious evidence proving that androgen deprivation therapy (ADT) would increase the risk of diabetes. To determine if ADT is associated with diabetes in men with prostate cancer, we carried out the present study. MATERIALS AND METHODS: We systematically searched Medline, Embase and the Cochrane Library Central Register through 2014. Studies comparing ADT vs control aimed at treating prostate cancer reporting diabetes as outcome were included. Data were extracted independently by two reviewers. This meta-analysis was reported based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses checklist. Observational studies were evaluated through the Meta analysis Of Observational Studies in Epidemiology checklist. RESULTS: Eight studies were identified with 65,695 ADT users and 91,893 non-ADT users. The pooled incidence of diabetes was 39% higher in ADT groups. A significant association was observed in the overall analysis (risk ratio [RR] 1.39, 95% confidence interval [CI] 1.27-1.53; P < 0.001). In subgroup analyses, diabetes was found to be significantly associated with gonadotropin-releasing hormone (GnRH) alone (RR 1.45, 95% CI 1.36-1.54; P < 0.001), GnRH plus oral antiandrogen (RR 1.40, 95% CI 1.01-1.93; P = 0.04) and orchiectomy (RR 1.34, 95% CI 1.20-1.50; P < 0.001), but not with antiandrogen alone (RR 1.33, 95% CI 0.75-2.36; P = 0.33). Diabetes was strongly related to long duration of ADT (RR 1.43, 95% CI 1.22-1.68; P < 0.001), and was slightly associated with short duration of ADT (RR 1.29, 95% CI 1.12-1.49; P = 0.0004). CONCLUSIONS: ADT, especially long duration (>6 months) of this treatment, GnRH alone, GnRH plus antiandrogen and orchiectomy can increase the incidence of diabetes. PMID- 27181719 TI - [Cell therapy for Parkinson's disease]. PMID- 27181720 TI - [Translational research of cell sheet-based myocardial regeneration therapy]. PMID- 27181721 TI - [Modeling muscular diseases by patient-derived iPS cells]. PMID- 27181722 TI - [Re-emerging reactive sulfur-containing compounds and their unique biological functions]. PMID- 27181723 TI - [Regulation of calcium signals via redox modification]. PMID- 27181724 TI - [Regulatory mechanism of cytotoxicity by reactive sulfur species]. PMID- 27181725 TI - [Functional chemical donors for investigation of reactive sulfide species]. PMID- 27181726 TI - [Reactive sulfur species-modified protein thiols: new methods for polysulfurated protein analysis]. PMID- 27181727 TI - [Development and perspective for the Biosimilar medicines]. PMID- 27181728 TI - [Pharmacology profile and clinical findings of bosutinib hydrate (Bosulif(r) Tablets)]. PMID- 27181729 TI - [Is the regulation of immune system in Alzheimer's disease effective? ]. PMID- 27181730 TI - Intestinal toxicity of oral warfarin intake in rats. AB - Though warfarin is extensively used in the prevention and treatment of thromboembolic processes in humans, adverse effects of warfarin therapy have been recognized. Intestinal hemorrhage is one of the hazards of anticoagulant therapy, but the mechanisms of warfarin toxicity are virtually unknown. In this work, the effects of 30 days oral warfarin (0.35 mg/l and 3.5 mg/l) intake on rat's gut were examined. Both doses resulted in prolongation of prothrombin time. Systemic effects of higher warfarin dose (increases in plasma AST, proteinuria, hematuria, changes in peripheral blood hematological parameters) were seen. Warfarin intake resulted in histologically evident tissue damage, leukocyte infiltration and intestinal inflammation [increases in myeloperoxidase activity, malondialdehyde content, superoxide dismutase and catalase activity, proinflammatory cytokine (IFN-gamma, IL-17) concentrations in intestinal homogenates]. In contrast, suppression of gut-draining mesenteric lymph node (MLN) cell activity [proliferation responsiveness, production of IFN-gamma and IL-17 to T lymphocyte mitogen Concanavalin A stimulation] was noted. Inhibition of regulatory cytokine IL-10 production by MLN cells, suggests commitment of MLN to the suppression of all inflammatory activities and creation of the microenvironment which is non permissive for induction of potentially harmful immune response. These novel findings indicate the need of staying alert for (adverse) effects of warfarin therapy. PMID- 27181731 TI - Trends in Use and Cost of Second-Generation Antipsychotics Among Children and Teens in Indiana Medicaid, 2004-2012. AB - OBJECTIVE: To replicate and extend a study by the Agency for Healthcare Research and Quality (AHRQ) and Rutgers on antipsychotic use among youths in Medicaid, the authors analyzed Indiana Medicaid claims from 2004 to 2012, extending the earlier study by focusing on second-generation antipsychotics, including both fee-for service (FFS) and non-FFS patients, and analyzing cost trends. METHODS: The authors evaluated the impact of several Indiana Medicaid policy changes on medication utilization and cost among children enrolled for at least one month during 2004-2012 (N=683,716-793,637), using an exhaustive antipsychotic list to search the database. RESULTS: Annual utilization rates for antipsychotics were 2% 3% but were much higher among foster children (10%-15%). Policies implemented in 2007 or later were associated with a significant plateauing of utilization in 2008-2012. CONCLUSIONS: Growth of second-generation antipsychotic utilization and costs was similar to trends described in the AHRQ-Rutgers study. Several containment strategies appeared effective in addressing these trends. PMID- 27181732 TI - Implementation of Integrated Health Homes and Health Outcomes for Persons With Serious Mental Illness in Los Angeles County. AB - OBJECTIVE: The Medicaid health home option of the Affordable Care Act provides a new opportunity to address the fragmented system of care for persons with serious mental illness. This study examined the implementation of integrated health homes in Los Angeles County. METHODS: Longitudinal data on client-reported physical health status, clinician-reported mental health recovery, and screening for common chronic conditions among 1,941 persons enrolled in integrated care programs for serious mental illness and chronic general medical illness were combined with site visit data measuring the level of integration of general medical and mental health care among ten integrated care programs. Various analyses were used to compare outcomes by level of program integration (generalized estimating equations for physical health status and mental health recovery and logistic regression and chi-square tests for screening for common chronic conditions and clinical risk factors). RESULTS: Clients in more highly integrated programs had greater improvements in physical health status and mental health recovery and higher rates of screening for common chronic conditions compared with clients in less integrated programs. They also had greater reductions in hypertension but a worrisome increase in prediabetes and diabetes. CONCLUSIONS: Highly integrated mental health and general medical programs were associated with greater improvements in health outcomes compared with less integrated programs. Additional research is necessary to identify predictors of integration, to determine which aspects of integration drive improvements in health outcomes, and to identify strategies to increase integration within less integrated programs. Efforts are needed to coordinate pharmacotherapy, including increased consideration of the metabolic effects of antipsychotic medication. PMID- 27181733 TI - A Randomized Clinical Trial of a Money Management Intervention for Veterans With Psychiatric Disabilities. AB - OBJECTIVE: The study evaluated an intervention to help veterans with psychiatric disabilities, who face a unique set of challenges concerning money management. METHODS: A randomized clinical trial was conducted of a brief (one to three hours) psychoeducational, recovery-oriented money management intervention called $teps for Achieving Financial Empowerment ($AFE). RESULTS: Analyses revealed no main effects on outcomes of random assignment to $AFE (N=67) or a control condition consisting of usual care (N=77). Veterans who reported using $AFE skills showed significantly lower impulsive buying, more responsible spending, higher rates of engaging in vocational activities, and greater number of work hours compared with veterans in the control condition. CONCLUSIONS: Findings have clinical implications for case management services involving informal money management assistance. Offering veterans with psychiatric disabilities a one-time money management intervention is unlikely to lead to substantial changes. Results imply that efforts to improve psychosocial outcomes among veterans must not only teach but also increase use of money management skills. PMID- 27181734 TI - National Trends in ADHD Diagnosis and Treatment: Comparison of Youth and Adult Office-Based Visits. AB - OBJECTIVES: The study objective was to assess national trends in the diagnosis of attention-deficit hyperactivity disorder (ADHD) in outpatient visits by comparing adults and youths. Also examined were recent stimulant prescribing patterns for ADHD visits by youths and adults. METHODS: Databases from the 1999-2010 National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey were used in this cross-sectional study to analyze outpatient visit data of youths (ages two to 17 years; unweighted N=112,404) and adults (ages 18-64; unweighted N=426,209). The 12-year trends in ADHD visits were assessed as a proportion of youth and adult visits. The interaction of time period and age group was added to multivariable and weighted logistic regression models to assess whether trends in ADHD diagnosis differed by age group. RESULTS: As a percentage of total visits, those involving an ADHD diagnosis were more common among youths than adults. However, from 1999 through 2010, the percentage of total visits involving a diagnosis of ADHD increased proportionally more among adult visits (from .3%, unweighted N=363 of 132,065, to .7%, unweighted N=1,015 of 154,764; adjusted odds ratio [AOR]=2.7, 95% confidence interval [CI]=2.1-3.7) than among youth visits (from 3.9%, unweighted N=2,033 of 36,263, to 5.2%, unweighted N=2,609 of 37,906; AOR=1.3, CI=1.1-1.6; p<.001). ADHD visits by adults compared with those by youths represented significantly greater proportions of females, Caucasians, patients with private insurance, and visits with a psychiatrist. Stimulant prescribing was common in ADHD visits regardless of age group (>70%). CONCLUSIONS: As a percentage of total office-based visits, those at which ADHD was diagnosed increased more among adults than among youths from 1999 to 2010. Further research is warranted on the appropriateness, benefit-risk, and policy implications of stimulant use among adults with ADHD. PMID- 27181735 TI - The ACA's Dependent Coverage Expansion and Out-of-Pocket Spending by Young Adults With Behavioral Health Conditions. AB - OBJECTIVE: Young adults with behavioral health conditions (mental or substance use disorders) often lack access to care. In 2010, the Affordable Care Act (ACA) extended eligibility for dependent coverage under private health insurance, allowing young adults to continue on family plans until age 26. The objective of this study was to analyze out-of-pocket (OOP) spending as a share of total health care expenditures for young adults with behavioral health conditions before and after the implementation of the ACA dependent care provision. The study examined the population of young adults with behavioral health conditions overall and by race and ethnicity. METHODS: The study analyzed 2008-2009 and 2011-2012 nationally representative data from the Medical Expenditure Panel Survey with zero-or-one inflated beta regression models in a difference-in-differences framework to estimate the impact of the ACA's dependent coverage expansion. OOP spending was examined as a share of total health care expenditures among young adults with behavioral health disorders. The study compared the treatment group of individuals ages 19-25 (unweighted N=1,158) with a group ages 27-29 (unweighted N=668). RESULTS: Young adults ages 19-25 with behavioral health disorders were significantly less likely than the older group to have high levels of OOP spending after the implementation of the ACA's dependent coverage expansion. The reduction was pronounced among young adults from racial-ethnic minority groups. CONCLUSIONS: The extension of health insurance coverage to young adults with behavioral health disorders has provided them with additional financial protection, which can be important given the low incomes and high debt burden that characterize the age group. PMID- 27181737 TI - Treat and Teach Our Students Well: College Mental Health and Collaborative Campus Communities. AB - This article presents a selective review of best practices for the psychiatric care of college student populations. It describes psychiatric advances in evidence-based practice for college students and offers a brief compendium for college health practitioners. College mental health services are delivered in a specialized milieu, designed to address many of the unique needs of college students and to support their successful scholastic advancement and graduation. Practical steps for implementing these best practices within the college community setting are identified, with a focus on the initial student evaluation, risk assessment, treatment planning and goal setting, and steps to optimize academic functioning during psychopharmacologic and nonpharmacologic treatment. At the center of these practices is the use of a collaborative team and psychoeducation that engages students to actively learn about their mental health. By applying common sense and evidence-based practices within interdisciplinary and student-centered services, college communities can effectively meet the mental health needs of their students and empower them to reach their educational goals. PMID- 27181736 TI - Patient Safety Events and Harms During Medical and Surgical Hospitalizations for Persons With Serious Mental Illness. AB - OBJECTIVE: This study explored the risk of patient safety events and associated nonfatal physical harms and mortality in a cohort of persons with serious mental illness. This group experiences high rates of medical comorbidity and premature mortality and may be at high risk of adverse patient safety events. METHODS: Medical record review was conducted for medical-surgical hospitalizations occurring during 1994-2004 in a community-based cohort of Maryland adults with serious mental illness. Individuals were eligible if they died within 30 days of a medical-surgical hospitalization and if they also had at least one prior medical-surgical hospitalization within five years of death. All admissions took place at Maryland general hospitals. A case-crossover analysis examined the relationships among patient safety events, physical harms, and elevated likelihood of death within 30 days of hospitalization. RESULTS: A total of 790 hospitalizations among 253 adults were reviewed. The mean number of patient safety events per hospitalization was 5.8, and the rate of physical harms was 142 per 100 hospitalizations. The odds of physical harm were elevated in hospitalizations in which 22 of the 34 patient safety events occurred (p<.05), including medical events (odds ratio [OR]=1.5, 95% confidence interval [CI]=1.3 1.7) and procedure-related events (OR=1.6, CI=1.2-2.0). Adjusted odds of death within 30 days of hospitalization were elevated for individuals with any patient safety event, compared with those with no event (OR=3.7, CI=1.4-10.3). CONCLUSIONS: Patient safety events were positively associated with physical harm and 30-day mortality in nonpsychiatric hospitalizations for persons with serious mental illness. PMID- 27181738 TI - "Poor Insight": A Capacity Perspective on Treatment Refusal in Serious Mental Illness. AB - For several decades, a protection standard has prevailed in determining the conditions under which a mental health provider, in concert with state authority, might intrude upon the civil rights of a person with serious mental illness. This approach contrasts with a treatment standard that guides consideration and assessment of incapacity in all other branches of medicine. This Open Forum examines the rationale, goals, and limits associated with involuntary intervention in serious mental illness compared with the rest of medicine. The authors believe that reviving a treatment standard that focuses on capacity among persons with serious mental illness would help build bridges between psychiatry and general medicine, between patients and providers, and between illness and recovery. PMID- 27181739 TI - Adoption of a Blended Training Curriculum for ACT in New York State. AB - Scant evidence exists in the literature for best practices in training assertive community treatment (ACT) teams to deliver highly effective services to consumers. This column describes a blended training curriculum, which includes both face-to-face and distance learning strategies, developed by the ACT Training Institute in New York State to meet the ongoing training needs of teams across New York State. Data on training uptake, which has steadily increased over time, are reported. The role of the state is crucial in driving adoption of training activities. The column also describes how the ACT Training Institute uses fidelity and outcome data to identify training needs. PMID- 27181740 TI - The preliminary clinical observation and analysis of childbearingage women with a history of iodine-131 treatment for Graves' disease. AB - Whether radioactive iodine treatment of Graves' disease (GD) during pregnancy will increase pregnancy loss and affect fetal development is still a matter of concern. From May 2005 to December 2015, 2,276 childbearing-age women with GD received iodine-131 treatment in our departments and were retrospectively enrolled in our study. When some of them were found to have been pregnant, their thyroid functions were measured every 4 weeks, in addition, thyroid-stimulating hormone (TSH) was measured 6 weeks after delivery. When necessary, levothyroxine or propylthiouracil (PTU) was given in order to control their TSH levels during pregnancy. Finally, 69 pregnant women (29 +/- 3.5 years old) and 1346 women who were not pregnant during the follow-up period were enrolled into this study. They were all hyperthyroid before or during pregnancy. Among 69 pregnant women, the administrated amount of iodine-131 was 254.9 +/- 99.9 MBq. Fifty patients became subclinically hypothyroid after treatment and were administrated levothyroxine (55 +/- 25 MUg/d). Seven patients were diagnosed with subclinical hyperthyroidism during pregnancy and they received PTU (25 +/- 12.5 mg/d). Twelve patients with normal thyroid function were also clinically followed. Among 69 women, 63 had a single birth, 3 had dizygotic twins, 2 had two pregnancies and 1 had a single twin birth. Sixty five babies were born full-term, while 9 were premature (4 +/- 1 weeks early) with birth weight 3.2 +/- 0.5 kg. Six new born babies were considered to be low birth weight infants (< 2.5 kg) while 5 were high birth weight (> 4 kg), but the weights of all the infants were within the normal range. During the period of observation to December 2015, all the infants were found to grow and develop normally. Among 1346 women who were not pregnant were in the further follow-up. Our study found no detrimental effects of the iodine-131 treatment in the pregnant women or their offspring so far. PMID- 27181741 TI - Iron Trichloride and Air Mediated Guanylation of Acylthioureas. An Ecological Route to Acylguanidines: Scope and Mechanistic Insights. AB - Recently we introduced iron trichloride as an environmentally benign and cost efficient reagent for the synthesis of N-benzoylguanidines. This highly attractive synthetic approach grants access to a broad spectrum of N benzoylguanidines under mild conditions in short reaction times. In this work we present an extended scope of our methodology along with the results obtained from mechanistic studies via in situ IR spectroscopy in combination with LC (liquid chromatography)-MS analyses. On the basis of these new mechanistic insights we were able to optimize the synthetic protocol and to develop an alternative mechanistic proposal. In this context the symbiotic roles of iron trichloride and oxygen in the guanylation process are highlighted. PMID- 27181742 TI - "No Good Deed Goes Unpunished": Ignaz Semmelweis and the Story of Puerperal Fever. AB - Ignac Fulop Semmelweis was born almost 200 years ago, in 1818, to a well-to-do middle class Hungarian family. He started law school in 1837, switched to medicine a year later, and graduated in 1844. PMID- 27181743 TI - Unusual cause of lymphangitis in a 2-year-old boy. PMID- 27181745 TI - Maternal supplementation of omega-3 fatty acids and micronutrients reduces cardiometabolic variables in pregnancy induced hypertension rats. AB - AIMS: Reports indicate that during pregnancy hypertension is known to have long term adverse effects both in the mother and offspring. However, the effect of maternal micronutrient supplementation on this association of in utero exposure and risk of non-communicable diseases in the later life remains unclear. The present study examines the effect of maternal micronutrient and omega-3 fatty acid supplementation either individual or in combination on cardiometabolic risk factors both in the mother and offspring using an animal model of hypertension. MAIN METHODS: Pregnant Wistar rats were randomly assigned to the following groups; control, PIH (Pregnancy induced hypertention) Induced, PIH+vitamin B12, PIH+ folic acid, PIH+omega-3 fatty acids and PIH+combined smicronutrient supplementation (vitamin B12+folic acid + omega-3 fatty acids). The dams and their offspring were shifted to a control diet after delivery and the offspring continued on these diets till 3mo of age. Hypertension during pregnancy was induced using l-Nitroarginine methylester (50mg/kgbody weight/day). KEY FINDINGS: Omega-3 fatty acid supplementation during pregnancy demonstrated lower levels (p<0.05) of plasma cholesterol while a combined supplementation of folic acid, vitamin B12 and omega 3 fatty acids demonstrated lower (p<0.05) triglyceride levels as compared to PIH induced dams. PIH induction increased (p<0.01) the triglyceride levels in the offspring at 3mo of age and maternal supplementation of either individual or combined micronutrients demonstrated lower (p<0.01) triglyceride levels. SIGNIFICANCE: Our findings have implications for planning intervention studies in women with pregnancy induced hypertension. PMID- 27181744 TI - Notch signalling regulates asymmetric division and inter-conversion between lgr5 and bmi1 expressing intestinal stem cells. AB - Rapidly cycling LGR5+ intestinal stem cells (ISCs) located at the base of crypts are the primary driver of regeneration. Additionally, BMI1 expression is correlated with a slow cycling pool of ISCs located at +4 position. While previous reports have shown interconversion between these two populations following tissue injury, we provide evidence that NOTCH signaling regulates the balance between these two populations and promotes asymmetric division as a mechanism for interconversion in the mouse intestine. In both in vitro and in vivo models, NOTCH suppression reduces the ratio of BMI1+/LGR5+ ISCs while NOTCH stimulation increases this ratio. Furthermore, NOTCH signaling can activate asymmetric division after intestinal inflammation. Overall, these data provide insights into ISC plasticity, demonstrating a direct interconversion mechanism between slow- and fast-cycling ISCs. PMID- 27181746 TI - Pharmacological profile of N-(2,6-dichlorophenyl)-2-(4-methyl-1 piperidinyl)acetamide, a novel analogue of lidocaine. AB - AIM: N-(2,6-Dichlorophenyl)-2-(4-methyl-1-piperidinyl)acetamide (LIA), a lidocaine analogue, has potential applications in treating neuropathic pain. The aim of this work was to characterize the pharmacological activity of LIA related with central nervous system and cardiovascular activity. METHODS: Anesthetic effect was tested in guinea pigs and mice. Ambulatory activity, anti-anxiety effect, sodium pentobarbital (PB)-induced hypnosis and pentylenetetrazol (PTZ) induced seizures test were evaluated in mice to determine the possible central nervous system activity. The cardiovascular activities in vivo and ex vivo were analyzed in rats. KEY FINDINGS: LIA (2%) presents, similar to lidocaine (2%), anesthetic activity on the corneal reflex, infiltration anesthesia and tail immersion test. LIA (1-100mg/kg, i.p.), similar to lidocaine (1-100mg/kg, i.p.), presents a dose-dependent sedative-hypnotic effect in mice. Both compounds did not produce anti-anxiety activity in mice. LIA did not prevent PTZ-induced seizures. However, LIA itself did not produce seizures at high doses in mice, as lidocaine does. LIA is a vasorelaxant compound for smooth muscle cells and presents hypotensive effect in vivo without increments to the heart rate significantly. SIGNIFICANCE: High doses of lidocaine produce seizures and vasoconstriction. In this study, we found that LIA shares a similar pharmacological profile as lidocaine's but without the primary adverse effects of seizures and vasoconstriction. PMID- 27181747 TI - A case of variant biochemical phenotype of Niemann-Pick disease type C accompanying savant syndrome. AB - A 40-year-old man was referred to our hospital because of vertical supranuclear gaze palsy, frequent sudden loss of muscle tonus and ataxia for several years. He had a history of prolonged neonatal jaundice. He was given a diagnosis of autism in his childhood, followed by a diagnosis of schizophrenia in his teenage. He also developed a savant skill of calendar calculating. (123)I-IMP-SPECT showed decreased cerebral blood flow in the left frontotemporal lobe as often seen in savant syndrome. Although genetic analysis of NPC1 and NPC2 revealed no pathogenic mutation, filipin staining of cultured fibroblasts from his biopsied skin revealed a certain amount of intracellular cholesterol storage pattern, indicating a variant biochemical phenotype of Niemann-Pick disease type C (NPC). The diagnosis of adulthood onset NPC is difficult and challenging, especially for neurologists, because the symptoms and signs are not as clear as those in the classical childhood onset NPC and this subtype is not yet widely known. However, the diagnosis can be made by a combination of filipin staining of fibroblast and/or gene analysis. As a disease-specific therapy for NPC has been approved in Japan, the diagnosis of NPC is of significance. PMID- 27181748 TI - Sporadic adult-onset neuronal intranuclear inclusion disease with the main presentation of repeated cerebellar ataxia: a case study. AB - A 66-year-old woman suddenly experienced unsteadiness while walking; she had experienced the same symptom before, but it had resolved immediately. Her neurological findings showed cerebellar ataxia, absence of tendon reflex in the extremities, and orthostatic hypotension. MRI with DWI of the brain showed linear high-intensity areas at the white matter just below the cerebral cortex. Therefore, we suspected neuronal intranuclear inclusion disease (NIID). In her cutaneous skin biopsy, intranuclear inclusion bodies, which tested positive for an anti-ubiquitin antibody and anti-p62 antibody, were observed in sweat gland cells and fibroblasts; therefore, we diagnosed her with NIID. As no one in her family had similar symptoms, this was a case of sporadic NIID. Adult-onset NIID with the main presentation of cerebellar ataxia is rare; in our case, this repeated acute-onset symptom was a unique manifestation of the condition. PMID- 27181749 TI - Autosomal recessive spinocerebellar ataxias in Japan. AB - Recent new sequencing techniques allow the identification of novel responsible genes for autosomal recessive spinocerebellar ataxias (ARCAs). However, the same phenotypes are sometimes attributed to the different responsible genes in ARCAs. On the contrary, the same responsible genes may cause heterogeneous phenotypes with respect to the age at onset, symptoms, and the severity of the disease progression. In addition, it is an important issue to clarify whether the gene mutations identified in Caucasian patients with infantile-onset ARCAs are also observed in Japanese patients with adult-onset ARCAs. In this article we review the characteristics of several ARCAs, the existence of which has been recently identified or confirmed in Japan. PMID- 27181751 TI - Are sex steroids essential for gonadal differentiation of the ornate frog, Microhyla ornata? AB - Knowledge about sensitivities and responses of amphibian larvae to sex steroids and the chemicals alike is the first step towards understanding and assessing the effect of diverse chemicals that interfere with gonadal development and other endocrine functions. Herein, we used Microhyla ornata to determine the role of sex steroids on its gonad differentiation and sex ratio. Our results show that the exposure to increasing concentrations of estradiol-17beta throughout larval development did not affect gonad differentiation resulting in 1:1 sex ratio at metamorphosis. But, females emerging from estradiol-17beta treatment had larger ovaries with larger sized follicles. Further, testes of some males contained lumens, the number of which was dose dependent. Similarly, exposure to testosterone propionate had negligible effects on gonad differentiation. However, the mean diameter of the largest follicles was smaller in treated ovaries. Treatment of tadpoles with tamoxifen had no effect on gonad differentiation and ovary development while testicular development was accelerated at the highest concentration. Similarly, treatment of tadpoles with cyproterone acetate had little effect on gonad differentiation as well as development, hence the sex ratios at the end of metamorphosis. Further, in tadpoles exposed to increasing concentrations of formestane, gonad differentiation was normal resulting in 1:1 sex ratio. Thus, in M. ornata, both estradiol and testosterone are essential for the development of ovaries and testes respectively but, they are not critical to gonadal differentiation. Hence, the effects of sex steroids and other endocrine disrupting chemicals could be species-specific; different species may have differential sensitivities to such chemicals. PMID- 27181750 TI - Peroxisomes are platforms for cytomegalovirus' evasion from the cellular immune response. AB - The human cytomegalovirus developed distinct evasion mechanisms from the cellular antiviral response involving vMIA, a virally-encoded protein that is not only able to prevent cellular apoptosis but also to inhibit signalling downstream from mitochondrial MAVS. vMIA has been shown to localize at mitochondria and to trigger their fragmentation, a phenomenon proven to be essential for the signalling inhibition. Here, we demonstrate that vMIA is also localized at peroxisomes, induces their fragmentation and inhibits the peroxisomal-dependent antiviral signalling pathway. Importantly, we demonstrate that peroxisomal fragmentation is not essential for vMIA to specifically inhibit signalling downstream the peroxisomal MAVS. We also show that vMIA interacts with the cytoplasmic chaperone Pex19, suggesting that the virus has developed a strategy to highjack the peroxisomal membrane proteins' transport machinery. Furthermore, we show that vMIA is able to specifically interact with the peroxisomal MAVS. Our results demonstrate that peroxisomes constitute a platform for evasion of the cellular antiviral response and that the human cytomegalovirus has developed a mechanism by which it is able to specifically evade the peroxisomal MAVS dependent antiviral signalling. PMID- 27181752 TI - Insulin-like signaling (IIS) responses to temperature, genetic background, and growth variation in garter snakes with divergent life histories. AB - The insulin/insulin-like signaling pathway (IIS) has been shown to mediate life history trade-offs in mammalian model organisms, but the function of this pathway in wild and non-mammalian organisms is understudied. Populations of western terrestrial garter snakes (Thamnophis elegans) around Eagle Lake, California, have evolved variation in growth and maturation rates, mortality senescence rates, and annual reproductive output that partition into two ecotypes: "fast living" and "slow-living". Thus, genes associated with the IIS network are good candidates for investigating the mechanisms underlying ecological divergence in this system. We reared neonates from each ecotype for 1.5years under two thermal treatments. We then used qPCR to compare mRNA expression levels in three tissue types (brain, liver, skeletal muscle) for four genes (igf1, igf2, igf1r, igf2r), and we used radioimmunoassay to measure plasma IGF-1 and IGF-2 protein levels. Our results show that, in contrast to most mammalian model systems, igf2 mRNA and protein levels exceed those of igf1 and suggest an important role for igf2 in postnatal growth in reptiles. Thermal rearing treatment and recent growth had greater impacts on IGF levels than genetic background (i.e., ecotype), and the two ecotypes responded similarly. This suggests that observed ecotypic differences in field measures of IGFs may more strongly reflect plastic responses in different environments than evolutionary divergence. Future analyses of additional components of the IIS pathway and sequence divergence between the ecotypes will further illuminate how environmental and genetic factors influence the endocrine system and its role in mediating life history trade-offs. PMID- 27181754 TI - Controlling particle deposit morphologies in drying nano-particle laden sessile droplets using substrate oscillations. AB - Sessile water droplets containing nano-silica particles are allowed to evaporate in the presence of driven substrate oscillations at chosen frequencies. Different mode shapes are observed at different oscillation frequencies. As reference, the evaporation of the same droplets is also observed under stationary conditions i.e. in the absence of any oscillations. For all cases, the deposit structures formed by the agglomeration of the nano-silica particles have been imaged. It has been observed that for the stationary droplets and for droplets whose oscillations are initiated close to the resonance of the lowest allowable oscillation mode, the structures are similar having larger spread over height, while for higher frequencies the structures are dome-like with more uniform outer dimensions. The possible reasons behind these structures are investigated using experimental techniques such as high-speed imaging of droplet oscillations, internal flow visualization and SEM imaging. Understanding of the underlying mechanisms behind the formation of these striking features is required for these methods to be applicable in larger scale drying operations or micro-device applications. Altogether a novel methodology has been presented and investigated for manipulating the morphological features in evaporating nano-particle laden sessile droplets. PMID- 27181753 TI - Role of clock genes in insulin secretion. PMID- 27181756 TI - Mental health and human trafficking. PMID- 27181755 TI - Cluster-randomized trial to improve the quality of diabetes management: The study for the efficacy assessment of the standard diabetes manual (SEAS-DM). AB - AIMS/INTRODUCTION: 'The Standard Diabetes Manual' has been developed by clinical researchers from multiple major institutions in Japan, such as the National Center for Global Health and Medicine, as a comprehensive disease management program, including collaboration between primary care physicians (PCPs) and specialist services. The present study evaluated the efficacy of the manual as a quality improvement strategy in diabetes care by PCPs. MATERIALS AND METHODS: A total of 42 PCPs in eight domestic districts of the Japan Medical Association were allocated to either the intervention group or the control group in a cluster randomized design. The PCPs in both groups were provided with a copy of the Diabetes Treatment Guide published by the Japan Diabetes Society, and the PCPs in the intervention group additionally received a copy of the manual and a 30-min relevant seminar at the inception of the intervention. The primary end-point was the adherence to the following performances as quality indicators: evaluation of retinopathy, and urinary albumin excretion measurements and serum creatinine measurements, as recommended by the Japan Medical Association. RESULTS: A total of 416 patients were enrolled by 36 PCPs. During the 1-year follow-up period, the proportion of PCPs who adhered to recommendation-concordant measurements of urinary albumin excretion was significantly higher in the intervention group than in the control group (adherence: 17.9% vs 5.3%, P = 0.016). The other parameters were not statistically different between the two groups. CONCLUSIONS: Implementation of 'The Standard Diabetes Manual' potentially leads to an improved quality of diabetes management by PCPs. PMID- 27181757 TI - Double remote electrochemical addressing and optical readout of electrochemiluminescence at the tip of an optical fiber. AB - In this work, we report an original strategy for the wireless electrochemical generation of light at the tip of an optical fiber bundle, coupled with a simultaneous remote readout. An optical fiber bundle coated with a nanometer-thin gold film acts as a dual platform, on the one hand to locally generate electrochemiluminescence (ECL) in a wireless manner by bipolar electrochemistry, and on the other hand to guide the resulting ECL signal. The light emission is triggered and collected at one end, transmitted by the waveguide and remotely detected at the opposite end. Integration of both functionalities at the level of the same miniaturized object leads to an unprecedented bipolar opto-electrode, allowing one to quantify the ECL intensity as a function of different parameters in a double remote approach with interesting potential applications, ranging from high-throughput catalyst screening to massive parallel biochemical analysis. PMID- 27181758 TI - The effect of the carbon nanotube buffer layer on the performance of a Li metal battery. AB - Lithium (Li) metal is one of the most promising candidates as an anode for the next-generation energy storage systems because of its high specific capacity and lowest negative electrochemical potential. But the growth of Li dendrites limits the application of the Li metal battery. In this work, a type of modified Li metal battery with a carbon nanotube (CNT) buffer layer inserted between the separator and the Li metal electrode was reported. The electrochemical results show that the modified batteries have a much better rate capability and cycling performance than the conventional Li metal batteries. The mechanism study by electrochemical impedance spectroscopy reveals that the modified battery has a smaller charge transfer resistance and larger Li ion diffusion coefficient during the deposition process on the Li electrode than the conventional Li metal batteries. Symmetric battery tests show that the interfacial behavior of the Li metal electrode with the buffer layer is more stable than the naked Li metal electrode. The morphological characterization of the CNT buffer layer and Li metal lamina reveals that the CNT buffer layer has restrained the growth of Li dendrites. The CNT buffer layer has great potential to solve the safety problem of the Li metal battery. PMID- 27181759 TI - [Prognosis prediction of febrile neutropenia by MASCC score: A retrospective study]. AB - INTRODUCTION: The score of the MASCC, by means of clinical criteria, estimates the risk of serious complications in patients with neutropenic fever induced by chemotherapy. METHODS: We retrospectively studied a cohort of patients hospitalized for a neutropenic fever and analyzed complications according to the criteria defined by the MASCC. RESULTS: Eighty-one neutropenic fevers in 71 patients were identified. Microbiological documentation was obtained in 33% of cases only. Fifty-eight patients (72%) presented with a MASCC score>=21 and were considered as low risk of complications. In the total population, 10 patients died during their hospitalizations for neutropenic fever, 7 in the high-risk group versus 3 in the low risk group, including 2 patients suffering from significant comorbidities not taken into account by MASCC score. Within the low risk group, presence of a metastatic disease and existence of 2 or more comorbidities were associated with a longer duration of hospitalization. CONCLUSION: This analysis suggests that the criteria of the MASCC are not always enough to thoroughly identify which patients were at risk of complications or could be treated through outpatient management. By better taking into account the comorbidities and tumoral stage, a better selection of the patients who are likely to receive an ambulatory treatment could be made. To date, hospitalization remains frequently necessary in neutropenic fevers, at least in its initial steps, and the place of the general practitioner remains to be better defined. PMID- 27181760 TI - [The surrogate: Partner in the shared decision-making]. AB - The legislative process of the surrogate appears to be unclear to health professionals and to patients and next of kin. To better adapt this process to the clinical practice our objective was here to document how the persons designated as surrogate perceived their role and how they described the difficulties encountered in oncology. METHODS: Qualitative survey with an ethnographic approach carried out in 2014-2015, fieldwork, face-to-face interviews (n=26 including 20 surrogates and 6 patients) in a mobile palliative care unit located at a Regional Comprehensive Cancer Centre. RESULTS: Close relationship, psychological and cognitive competences were the main attribute to designate a surrogate. Perceived roles included the fact to be involved in decisions, to protect the patient, to be present, and to be a messenger. This process gives the next of kin the feeling to be part of the patient management. In the context of divorced families, it sometimes allows to rehabilitate and to reinforce the affective links. Our data highlight the confusion between the designation of the 'person to call' and 'the surrogate'. DISCUSSION: Our results highlight the 'surrogate' protective role of the patient, and the positive sides of the process, in particular in the context of divorced/rebuilt families. We recommend splitting the process to designate the 'person to call' and the 'surrogate', as administrative and medical duties, respectively. PMID- 27181761 TI - High-resolution characterisation of the aging brain using simultaneous quantitative susceptibility mapping (QSM) and R2* measurements at 7T. AB - Quantitative susceptibility mapping (QSM) has recently emerged as a novel magnetic resonance imaging (MRI) method to detect non-haem iron deposition, calcifications, demyelination and vascular lesions in the brain. It has been suggested that QSM is more sensitive than the more conventional quantifiable MRI measure, namely the transverse relaxation rate, R2*. Here, we conducted the first high-resolution, whole-brain, simultaneously acquired, comparative study of the two techniques using 7Tesla MRI. We asked which of the two techniques would be more sensitive to explore global differences in tissue composition in elderly adults relative to young subjects. Both QSM and R2* revealed strong age-related differences in subcortical regions, hippocampus and cortical grey matter, particularly in superior frontal regions, motor/premotor cortices, insula and cerebellar regions. Within the basal ganglia system-but also hippocampus and cerebellar dentate nucleus-, QSM was largely in agreement with R2* with the exception of the globus pallidus. QSM, however, provided superior anatomical contrast and revealed age-related differences in the thalamus and in white matter, which were otherwise largely undetected by R2* measurements. In contrast, in occipital cortex, age-related differences were much greater with R2* compared to QSM. The present study, therefore, demonstrated that in vivo QSM using ultra high field MRI provides a novel means to characterise age-related differences in the human brain, but also combining QSM and R2* using multi-gradient recalled echo imaging can potentially provide a more complete picture of mineralisation, demyelination and/or vascular alterations in aging and disease. PMID- 27181762 TI - fMRI-constrained source analysis reveals early top-down modulations of interference processing using a flanker task. AB - Usually, incongruent flanker stimuli provoke conflict processing whereas congruent flankers should facilitate task performance. Various behavioral studies reported improved or even absent conflict processing with correctly oriented selective attention. In the present study we attempted to reinvestigate these behavioral effects and to disentangle neuronal activity patterns underlying the attentional cueing effect taking advantage of a combination of the high temporal resolution of Electroencephalographic (EEG) and the spatial resolution of functional magnetic resonance imaging (fMRI). Data from 20 participants were acquired in different sessions per method. We expected the conflict-related N200 event-related potential (ERP) component and areas associated with flanker processing to show validity-specific modulations. Additionally, the spatio temporal dynamics during cued flanker processing were examined using an fMRI constrained source analysis approach. In the ERP data we found early differences in flanker processing between validity levels. An early centro-parietal relative positivity for incongruent stimuli occurred only with valid cueing during the N200 time window, while a subsequent fronto-central negativity was specific to invalidly cued interference processing. The source analysis additionally pointed to separate neural generators of these effects. Regional sources in visual areas were involved in conflict processing with valid cueing, while a regional source in the anterior cingulate cortex (ACC) seemed to contribute to the ERP differences with invalid cueing. Moreover, the ACC and precentral gyrus demonstrated an early and a late phase of congruency-related activity differences with invalid cueing. We discuss the first effect to reflect conflict detection and response activation while the latter more likely originated from conflict monitoring and control processes during response competition. PMID- 27181763 TI - Human subthalamic nucleus-medial frontal cortex theta phase coherence is involved in conflict and error related cortical monitoring. AB - The medial prefrontal cortex (mPFC) is thought to control the shift from automatic to controlled action selection when conflict is present or when mistakes have been recently committed. Growing evidence suggests that this process involves frequency specific communication in the theta (4-8Hz) band between the mPFC and the subthalamic nucleus (STN), which is the main target of deep brain stimulation (DBS) for Parkinson's disease. Key in this hypothesis is the finding that DBS can lead to impulsivity by disrupting the correlation between higher mPFC oscillations and slower reaction times during conflict. In order to test whether theta band coherence between the mPFC and the STN underlies adjustments to conflict and to errors, we simultaneously recorded mPFC and STN electrophysiological activity while DBS patients performed an arrowed flanker task. These recordings revealed higher theta phase coherence between the two sites during the high conflict trials relative to the low conflict trials. These differences were observed soon after conflicting arrows were displayed, but before a response was executed. Furthermore, trials that occurred after an error was committed showed higher phase coherence relative to trials that followed a correct trial, suggesting that mPFC-STN connectivity may also play a role in error related adjustments in behavior. Interestingly, the phase coherence we observed occurred before increases in theta power, implying that the theta phase and power may influence behavior at separate times during cortical monitoring. Finally, we showed that pre-stimulus differences in STN theta power were related to the reaction time on a given trial, which may help adjust behavior based on the probability of observing conflict during a task. PMID- 27181764 TI - Imaging whole-brain cytoarchitecture of mouse with MRI-based quantitative susceptibility mapping. AB - The proper microstructural arrangement of complex neural structures is essential for establishing the functional circuitry of the brain. We present an MRI method to resolve tissue microstructure and infer brain cytoarchitecture by mapping the magnetic susceptibility in the brain at high resolution. This is possible because of the heterogeneous magnetic susceptibility created by varying concentrations of lipids, proteins and irons from the cell membrane to cytoplasm. We demonstrate magnetic susceptibility maps at a nominal resolution of 10-MUm isotropic, approaching the average cell size of a mouse brain. The maps reveal many detailed structures including the retina cell layers, olfactory sensory neurons, barrel cortex, cortical layers, axonal fibers in white and gray matter. Olfactory glomerulus density is calculated and structural connectivity is traced in the optic nerve, striatal neurons, and brainstem nerves. The method is robust and can be readily applied on MRI scanners at or above 7T. PMID- 27181765 TI - Different role of zinc transporter 8 between type 1 diabetes mellitus and type 2 diabetes mellitus. AB - Diabetes can be simply classified into type 1 diabetes mellitus and type 2 diabetes mellitus. Zinc transporter 8 (ZnT8), a novel islet autoantigen, is specifically expressed in insulin-containing secretory granules of beta-cells. Genetic studies show that the genotypes of SLC30A8 can determine either protective or diabetogenic response depending on environmental and lifestyle factors. The ZnT8 protein expression, as well as zinc content in beta-cells, was decreased in diabetic mice. Thus, ZnT8 might participate in insulin biosynthesis and release, and subsequently involved deteriorated beta-cell function through direct or indirect mechanisms in type 1 diabetes mellitus and type 2 diabetes mellitus. From a clinical feature standpoint, the prevalence of ZnT8A is gradiently increased in type 2 diabetes mellitus, latent autoimmune diabetes in adults and type 1 diabetes mellitus. The frequency and epitopes of ZnT8-specific T cells and cytokine release by ZnT8-specific T cells are also different in diabetic patients and healthy controls. Additionally, the response to ZnT8 administration is also different in type 1 diabetes mellitus and type 2 diabetes mellitus. In the present review, we summarize the literature about clinical aspects of ZnT8 in the pathogenesis of diabetes, and suggest that ZnT8 might play a different role between type 1 diabetes mellitus and type 2 diabetes mellitus. PMID- 27181766 TI - Electrostatic networks control plug stabilization in the PapC usher. AB - The PapC usher, a beta-barrel pore in the outer membrane of uropathogenic Escherichia coli, is used for assembly of the P pilus, a key virulence factor in bacterial colonization of human kidney cells. Each PapC protein is composed of a 24-stranded beta-barrel channel, flanked by N- and C-terminal globular domains protruding into the periplasm, and occluded by a plug domain (PD). The PD is displaced from the channel towards the periplasm during pilus biogenesis, but the molecular mechanism for PD displacement remains unclear. Two structural features within the beta-barrel, an alpha-helix and beta5-6 hairpin loop, may play roles in controlling plug stabilization. Here we have tested clusters of residues at the interface of the plug, barrel, alpha-helix and hairpin, which participate in electrostatic networks. To assess the roles of these residues in plug stabilization, we used patch-clamp electrophysiology to compare the activity of wild-type and mutant PapC channels containing alanine substitutions at these sites. Mutations interrupting each of two salt bridge networks were relatively ineffective in disrupting plug stabilization. However, mutation of two pairs of arginines located at the inner and the outer surfaces of the PD resulted in an enhanced propensity for plug displacement. One arginine pair involved in a repulsive interaction between the linkers that tether the plug to the beta-barrel was particularly sensitive to mutation. These results suggest that plug displacement, which is necessary for pilus assembly and translocation, may require a weakening of key electrostatic interactions between the plug linkers, and the plug and the alpha-helix. PMID- 27181767 TI - Effects of breast-feeding compared with formula-feeding on preterm infant body composition: a systematic review and meta-analysis. AB - We conducted a systematic review and meta-analysis to compare the effect of breast-feeding and formula-feeding on body composition of preterm infants. We searched the literature using PubMed, Cochrane Central Library Issue, Ovid (Medline), Embase and other resources such as Google Scholar, electronic databases and bibliographies of relevant articles; two reviewers collected and extracted data independently. All the authors assessed risk of bias independently using the Newcastle-Ottawa Scale (NOS). A fixed-effects meta-analysis was undertaken with RevMan 5 software (The Cochrane Collaboration) using the inverse variance method (P>=0.05; chi 2 test). In contrast, a random-effects meta analysis was carried out. Altogether, 630 articles were identified using search strategy, and the references within retrieved articles were also assessed. A total of six studies were included in this systematic review. In formula-fed infants, fat mass was higher at term (mean difference 0.24 (95 % CI 0.17, 0.31) kg), fat-free mass was higher at 36 weeks of gestational (mean difference 0.12 (95 % CI 0.04, 0.21) kg) and the percentage of fat mass was higher at 36 weeks of gestation (mean difference 3.70 (95 % CI 1.81, 5.59) kg) compared with breast-fed infants. Compared with breast-feeding, formula-feeding is associated with altered body composition from birth to term in preterm infants. The effects of formula feeding on preterm infant body composition from term to 12-month corrected age are inconclusive in our study. Well-designed studies are required in the future to explore the effects of formula-feeding compared with breast-feeding. PMID- 27181769 TI - More trouble with FGF23: a novel role in systemic immunosuppression. AB - A recent study describes impaired neutrophil function as another adverse effect of the excessive levels of FGF23 found in the circulation of patients with chronic kidney disease. These findings shed light on the mechanisms by which chronic kidney disease leads to systemic immunosuppression. PMID- 27181770 TI - ISCHEMIA in chronic kidney disease: improving the representation of patients with chronic kidney disease in cardiovascular trials. AB - Despite the high cardiovascular risk associated with chronic kidney disease, a recent systematic review confirmed that patients with kidney disease remain underrepresented in cardiovascular trials. Two ongoing trials are assessing the risk:benefit of aggressive evaluation and intervention for ischemic heart disease in patients with advanced chronic kidney disease. PMID- 27181771 TI - Activin receptor IIA ligand trap in chronic kidney disease: 1 drug to prevent 2 complications-or even more? AB - Vascular calcification and kidney fibrosis are 2 important features of chronic kidney disease. Bone morphogenetic proteins/growth differentiation factors and their receptors are implicated in the pathogenesis of both processes. Modulation of the bone morphogenetic protein/growth differentiation factor pathways by a soluble chimeric protein that contains the activin receptor IIA (ActRIIA) domain and acts as an ActRIIA ligand trap for activin and other ligands could become a new therapeutic strategy for vascular calcification and kidney fibrosis in chronic kidney disease. PMID- 27181772 TI - Unlocking the code: mining the urinary proteome after renal transplantation. AB - Diagnosis of transplant dysfunction usually requires kidney biopsy. Sidgel et al. compared urinary proteomics with matched kidney biopsies to develop a biomarker panel to differentiate acute rejection, BK viral nephropathy, and chronic allograft nephropathy. The results suggest that monitoring a panel of urinary peptides may ultimately facilitate noninvasive diagnosis and management of common transplant complications. PMID- 27181773 TI - Unraveling the mechanisms of progressive peritoneal membrane fibrosis. AB - Continuous glucose exposure contributes to severe ultrafiltration failure in peritoneal dialysis. In their study, Wang et al. describe a mechanistic pathway involving direct activation by glucose of mesothelial cell protein kinase C alpha that, when blocked, or absent in a mouse knockout model, prevents fibrosis and the associated reduction in ultrafiltration. Interestingly, this pathway involves the 3 main mechanisms of membrane injury (inflammation, neoangiogenesis, and fibrogenesis), offering a potential target for therapeutic intervention. PMID- 27181774 TI - Sleepless in CKD: a novel risk factor for CKD progression? AB - Disorders of sleep have been associated with adverse outcomes in both the general population and in patients with chronic kidney disease. McMullan et al. add to this literature by demonstrating an association between short sleep duration and more rapid decline in glomerular filtration rate. We discuss the potential implications of these results but also offer some caution in over-interpretation of the data, given limitations in both the assessment of sleep as well as the kidney outcomes. PMID- 27181775 TI - Statins for hemodialysis patients with diabetes? Long-term follow-up endorses the original conclusions of the 4D Study. AB - The clinical benefits of statins in dialysis patients are unproven. New follow-up data from the 4D Study indicate no clear reduction in cardiovascular events among patients with type-2 diabetes. Assessing outcomes 7.4 years beyond the randomization period (20 mg atorvastatin versus placebo), no differences in a composite cardiovascular outcome were observed and no safety concerns emerged. Current Kidney Disease: Improving Global Outcomes (KDIGO) guidelines do not need updating based on these new data. PMID- 27181776 TI - Controversies and research agenda in nephropathic cystinosis: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) Controversies Conference. AB - Nephropathic cystinosis is an autosomal recessive metabolic, lifelong disease characterized by lysosomal cystine accumulation throughout the body that commonly presents in infancy with a renal Fanconi syndrome and, if untreated, leads to end stage kidney disease (ESKD) in the later childhood years. The molecular basis is due to mutations in CTNS, the gene encoding for the lysosomal cystine-proton cotransporter, cystinosin. During adolescence and adulthood, extrarenal manifestations of cystinosis develop and require multidisciplinary care. Despite substantial improvement in prognosis due to cystine-depleting therapy with cysteamine, no cure of the disease is currently available. Kidney Disease: Improving Global Outcomes (KDIGO) convened a Controversies Conference on cystinosis to review the state-of-the-art knowledge and to address areas of controversies in pathophysiology, diagnostics, monitoring, and treatment in different age groups. More importantly, promising areas of investigation that may lead to optimal outcomes for patients afflicted with this lifelong, systemic disease were discussed with a research agenda proposed for the future. PMID- 27181778 TI - No apparent link between serum Klotho and phosphate in human chronic kidney disease. PMID- 27181779 TI - Serum anti-PLA2R antibodies may be present before clinical manifestations of membranous nephropathy. PMID- 27181777 TI - Loss of Glis2/NPHP7 causes kidney epithelial cell senescence and suppresses cyst growth in the Kif3a mouse model of cystic kidney disease. AB - Enlargement of kidney tubules is a common feature of multiple cystic kidney diseases in humans and mice. However, while some of these pathologies are characterized by cyst expansion and organ enlargement, in others, progressive interstitial fibrosis and kidney atrophy prevail. The Kif3a knockout mouse is an established non-orthologous mouse model of cystic kidney disease. Conditional inactivation of Kif3a in kidney tubular cells results in loss of primary cilia and rapid cyst growth. Conversely, loss of function of the gene GLIS2/NPHP7 causes progressive kidney atrophy, interstitial inflammatory infiltration, and fibrosis. Kif3a null tubular cells have unrestrained proliferation and reduced stabilization of p53 resulting in a loss of cell cycle arrest in the presence of DNA damage. In contrast, loss of Glis2 is associated with activation of checkpoint kinase 1, stabilization of p53, and induction of cell senescence. Interestingly, the cystic phenotype of Kif3a knockout mice is partially rescued by genetic ablation of Glis2 and pharmacological stabilization of p53. Thus, Kif3a is required for cell cycle regulation and the DNA damage response, whereas cell senescence is significantly enhanced in Glis2 null cells. Hence, cell senescence is a central feature in nephronophthisis type 7 and Kif3a is unexpectedly required for efficient DNA damage response and cell cycle arrest. PMID- 27181780 TI - Limitations of using the Chronic Kidney Disease-Epidemiology Collaboration equation for measuring renal function in obese populations. PMID- 27181781 TI - Cyclical cyclophosphamide and steroids is effective in resistant or relapsing nephrotic syndrome due to M-type phospholipase A2 receptor-related membranous nephropathy after tacrolimus therapy. PMID- 27181782 TI - Phospholipase A2 receptor staining is absent in many kidney biopsies with early stage membranous glomerulonephritis. PMID- 27181783 TI - Shed a light on intradialytic calcium mass balance. PMID- 27181784 TI - Glomerular epithelial cells in secondary focal segmental glomerulosclerosis. PMID- 27181785 TI - The Authors Reply. PMID- 27181786 TI - Ingelfinger JR, Kalantar-Zadeh K, Schaefer F; for the World Kidney Day Steering Committee. Averting the legacy of kidney disease-focus on childhood. Kidney Int. 2016;89:512-518. PMID- 27181787 TI - Collagenofibrotic glomerulopathy. PMID- 27181788 TI - Pseudoxanthoma elasticum and nephrocalcinosis. PMID- 27181789 TI - The Case | Rapidly progressing polyneuropathy in a dialysis patient. PMID- 27181791 TI - Iodine-Promoted Oxidative Cross-Coupling of Unprotected Anilines with Methyl Ketones: A Site-Selective Direct C-H Bond Functionalization to C4-Dicarbonylation of Anilines. AB - An unprecedented direct dual C-H bond functionalization of unprotected anilines and methyl ketones has been demonstrated. It is the first example of iodine promoted highly chemo- and site-selective oxidative C-H/C-H cross-coupling of anilines and methyl ketones to furnish the C4-dicarbonylation of anilines in moderate to good yields. Moreover, coproduct HI acted as a catalyst in the reaction. The salient feature of this approach is unprecedented C-H functionalization rather than N-H functionalization of unprotected anilines. PMID- 27181790 TI - Bremelanotide for female sexual dysfunctions in premenopausal women: a randomized, placebo-controlled dose-finding trial. AB - AIM: Evaluate efficacy/safety of bremelanotide (BMT), a melanocortin-receptor-4 agonist, to treat female sexual dysfunctions in premenopausal women. METHODS: Patients randomized to receive placebo or BMT 0.75, 1.25 or 1.75 mg self administered subcutaneously, as desired, over 12 weeks. Primary end point was change in satisfying sexual events/month. Secondary end points included total score changes on female sexual function index and female sexual distress scale desire/arousal/orgasm. RESULTS: Efficacy data, n = 327. For 1.25/1.75-mg pooled versus placebo, mean changes from baseline to study end were +0.7 versus +0.2 satisfying sexual events/month (p = 0.0180), +3.6 versus +1.9 female sexual function index total score (p = 0.0017), -11.1 versus -6.8 female sexual distress scale-desire/arousal/orgasm total score (p = 0.0014). Adverse events: nausea, flushing, headache. CONCLUSION: In premenopausal women with female sexual dysfunctions, self-administered, as desired, subcutaneous BMT was safe, effective, and well tolerated (NCT01382719). PMID- 27181792 TI - Radiologic response to radiation therapy concurrent with temozolomide for progressive simple dysembryoplastic neuroepithelial tumor. AB - Dysembryoplastic neuroepithelial tumors (DNETs) are low-grade neuroglial tumors that are traditionally considered to be benign hamartoma-like mass lesions. Malignant transformation and disease progression have been reported in complex DNETs. We report a case of a simple DNET with disease progression following subtotal resection. A 34-year-old woman underwent craniotomy with subtotal resection of a large nonenhancing right temporal lobe and insular mass. Histopathological analysis revealed a simple DNET. Magnetic resonance imaging obtained 6 months after surgery demonstrated disease progression with no enhancement or change in signal characteristics. Following concurrent therapy with temozolomide and external beam radiation therapy, a significant radiologic response was observed. Progressive DNET with malignant transformation exhibits predominantly glial transformation and occurs predominantly in complex DNETs. The histological classification of DNETs into simple, complex, and nonspecific are reviewed. Contrast-enhancing regions are more frequently seen in complex tumors, with nonenhancing regions having fewer complex histologic features. Close clinical and radiographic follow-up is important in all cases of DNET. Following tumor progression, radiation therapy with concurrent and adjuvant temozolomide chemotherapy may be an effective treatment. PMID- 27181793 TI - Simple, Reversible, and Fast Modulation in Superwettability, Gradient, and Adsorption by Counterion Exchange on Self-Assembled Monolayer. AB - A simple fabrication method for preparation of surfaces able to switch from superhydrophobic to superhydrophilic state in a reversible and fast way is described. A self-assembled monolayer (SAM) consisting of quaternary ammonium group with aliphatic tail bearing terminal thiol functionality was created on gold nano/microstructured and gold planar surfaces, respectively. A rough nano/microstructured surface was prepared by galvanic reaction on a silicon wafer. The reversible counterion exchange on the rough surface resulted in a switchable contact angle between <5 degrees and 151 degrees . The prewetted rough surface with Cl(-) as a counterion possesses a superoleophobic underwater character. The kinetics of counterion exchanges suggests a long hydration process and strong electron ion pairing between quaternary ammonium group and perfluorooctanoate counterion. Moreover, a wettability gradient from superhydrophobic to superhydrophilic can be formed on the modified rough gold surface in a robust and simple way by passive incubation of the substrate in a counterion solution and controlled by ionic strength. Furthermore, adsorption of gold nanoparticles to modified plain gold surface can be controlled to a high extent by counterions present on the SAM layer. PMID- 27181794 TI - Anti-rheumatic activity of Ananas comosus fruit peel extract in a complete Freund's adjuvant rat model. AB - CONTEXT: Rheumatoid arthritis is a chronic, autoimmune and systemic inflammatory disease, which targets synovial joints leading to joint destruction mediated in part by migration of inflammatory cells into the synovial tissue. OBJECTIVE: The present study evaluates the anti-rheumatic effect of a methanol extract of Ananas comosus (L.) Merr. (Bromeliaceae) peel in rats. MATERIALS AND METHODS: Anti rheumatic activity of crude extract of peels of A. comosus in complete Freund's induced arthritis model in rats was studied at doses of 50, 100, 250 and 500 mg/kg b.w. for 21 days. Parameters such as paw size, levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), C-reactive proteins (CRP) and prostaglandins (PGE2) were analysed. RESULTS: Oral administration of the extract significantly reduced the swelling in the paw of rats (EC50 65.1 +/- 2.95 mg/kg b.w.) with a maximal inhibition of 77.01 +/- 10.53% on 21st day at 500 mg/kg b.w. The extract also significantly reduced the levels of SOD, CAT and GPx in liver (EC50 26.84 +/- 16.37, 68.37 +/- 19.22, 106.54 +/- 34.81 mg/kg b.w., respectively), kidney (EC50 261.75 +/- 81.5, 176.38 +/- 8.08, 14.32 +/- 6.64, mg/kg b.w., respectively) and spleen (EC50 152.14 +/- 39.57, 83.97 +/- 14.6, 47.1 +/- 10.45 mg/kg b.w., respectively); and CRP (EC50 36.37 +/- 12.4 mg/kg b.w.) and PGE2 (EC50 191.06 +/- 71.54 mg/kg b.w.) in tissue homogenate and serum, respectively, at 500 mg/kg b.w. as compared to arthritic control group. DISCUSSION AND CONCLUSION: These results suggest that A. comosus fruit peel extract exerts anti-rheumatic activity. PMID- 27181821 TI - Staging of prostatic carcinoma at 1.5-T MRI: correlation of a simplified MRI exam with whole-mount radical prostatectomy specimens. AB - OBJECTIVE: To retrospectively analyze the accuracy of simplified multiparametric MRI at 1.5 T for local staging by using whole-mount-section histopathological analysis as the standard of reference. METHODS: 123 consecutive patients underwent T2 weighted, T1 weighted and diffusion-weighted MRI without endorectal coil prior to radical prostatectomy. The accuracy of predicting extracapsular extension (ECE) (T3a) was assessed using direct signs or the combination of direct and indirect signs of extraprostatic extension. The accuracy of predicting seminal vesicle invasion (T3b) was evaluated, taking into account different routes of seminal vesicle involvement. Finally, adjacent organ invasion (T4) was evaluated in this patient population. RESULTS: Histopathology showed T3a, T3b and T4 in 61, 28 and 9 cases, respectively. The use of direct signs of extraprostatic extension showed a sensitivity of 57.4% and specificity of 91.9%. The combination of direct signs and indirect signs improved sensitivity (85.2%) at the expense of moderate loss of specificity (83.9%). MR sensitivity for the detection of seminal vesicle invasion was low (53.6%); however, it was dependent on the route of seminal vesicle tumour infiltration. MR sensitivity and specificity for adjacent organ invasion were 88.9% and 99.1%. CONCLUSION: Simplified MRI study at 1.5 T provides a relatively high sensitivity for detecting ECE (T3a) when using the combination of indirect and direct signs. However, this high sensitivity reading is at the cost of a moderate loss of specificity. Invasion of the seminal vesicles (T3b) occurs most often along the ejaculatory duct complex with low MR sensitivity. ADVANCES IN KNOWLEDGE: Simplified MRI study at 1.5 T without endorectal coil could be used for the local T staging of prostate cancer. PMID- 27181822 TI - [Tattoo skin reactions: Management and treatment algorithm]. AB - So-called "allergic" reactions to ink or colouring agents constitute the main current complication associated with tattoos that lead individuals to consult. However, general practitioners are frequently at a loss about how to manage such complications. In order to assist clinicians in their daily practice, we propose an update of the modes of managing allergic reactions to tattoos, and we offer a therapeutic scale and a decision-making algorithm. PMID- 27181823 TI - [Bestiaries in clinical dermatology]. AB - Metaphors have always played a role in the medical tradition and in dermatology too. Beyond their initially playful aspect, metaphors offer a way of rapidly identifying a lesion and of linking it to one or more diseases. They also play a role in the education of medical students and residents by making it easier to memorise different diseases. Herein we discuss "animal" metaphors. PMID- 27181824 TI - Remembering Claes Hellerstrom and those around him. PMID- 27181826 TI - Erratum. PMID- 27181825 TI - Claes Hellerstrom and Cartesian diver microrespirometry. AB - Cartesian diver microrespirometry was introduced by Claes Hellerstrom at the Department of Histology/Medical Cell Biology at Uppsala University, Sweden, to determine rates of oxygen consumption in islets of Langerhans. The theory behind this method is touched upon and the main findings described. Glucose-stimulated beta cell respiration significantly contributes to increased ATP generation, which is a prerequisite for stimulated insulin secretion and synthesis. This has had major implications for understanding the beta cell stimulus-secretion coupling. PMID- 27181827 TI - Neural correlates of auditory working memory. PMID- 27181828 TI - Assessment of the relationship between non-alcoholic fatty liver disease and diabetic complications. AB - AIMS/INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder of the liver. The relationship between NAFLD and type 2 diabetes remains largely unknown. The aim of the present study was to determine the incidence of complications arising from the interaction between NAFLD and type 2 diabetes. MATERIALS AND METHODS: A total of 212 individuals with type 2 diabetes were included in the study. The presence of NAFLD was determined in individuals using abdominal ultrasonography for the diagnosis of fatty liver disease. Patients were divided into three groups based on the duration of diabetes and NAFLD diagnosis. Type 2 diabetes patients were placed in group A; patients with type 2 diabetes longer than NAFLD were placed in group B; and patients with NAFLD longer than type 2 diabetes were placed in group C. All individuals had undergone electrocardiogram, blood pressure measurements, and thorough medical history and physical examinations (Doppler ultrasound, electrophysiology, fundoscopy, cardiac computed tomography). Laboratory measurements included fasting blood glucose, glycated hemoglobin, oral glucose tolerance test, liver and renal function, lipid profile, and urinary albumin excretion. RESULTS: Compared with groups A and B, the patients of group C showed a higher prevalence of significant coronary artery disease and hypertension (P < 0.05). Compared with groups A and B, the patients of group C showed a lower prevalence of diabetic retinopathy and diabetic peripheral neuropathy (P < 0.05). There was no significant difference in the prevalence of diabetic nephropathy among the three groups (P > 0.05). CONCLUSIONS: NAFLD combined with type 2 diabetes is associated with the presence of significant coronary artery disease and hypertension. PMID- 27181829 TI - Validation of a procedure for the analysis of 226Ra in naturally occurring radioactive materials using a liquid scintillation counter. AB - An analytical procedure for detecting 226Ra in naturally occurring radioactive materials (NORMs) using a liquid scintillation counter (LSC) was developed and validated with reference materials (zircon matrix, bauxite matrix, coal fly ash, and phosphogypsum) that represent typical NORMs. The 226Ra was released from samples by a fusion method and was separated using sulfate-coprecipitation. Next, a 222Rn-emanation technique was applied for the determination of 226Ra. The counting efficiency was 238 +/- 8% with glass vials. The recovery for the reference materials was 80 +/- 11%. The linearity of the method was tested with different masses of zircon matrix reference materials. Using 15 types of real NORMs, including raw materials and by-products, this LSC method was compared with gamma-spectrometry, which had already been validated for 226Ra analysis. The correlation coefficient for the results from the LSC method and gamma spectrometry was 0.993 +/- 0.058. PMID- 27181830 TI - Re: Karim Fizazi, Kim N. Chi, Johann S. de Bono, et al. Low Incidence of Corticosteroid-associated Adverse Events on Long-term Exposure to Low-dose Prednisone Given with Abiraterone Acetate to Patients with Metastatic Castration resistant Prostate Cancer. Eur Urol. In press. http://dx.doi.org/10.1016/j.eururo.2016.02.035: Corticosteroid-associated Adverse Events in Elderly Patients. PMID- 27181831 TI - The Cigarette and the Sperm: A Fatal Liaison? PMID- 27181833 TI - From brittle to ductile: a structure dependent ductility of diamond nanothread. AB - As a potential building block for the next generation of devices/multifunctional materials that are spreading in almost every technology sector, one-dimensional (1D) carbon nanomaterial has received intensive research interests. Recently, a new ultra-thin diamond nanothread (DNT) has joined this palette, which is a 1D structure with poly-benzene sections connected by Stone-Wales (SW) transformation defects. Using large-scale molecular dynamics simulations, we found that this sp(3) bonded DNT can transition from brittle to ductile behaviour by varying the length of the poly-benzene sections, suggesting that DNT possesses entirely different mechanical responses than other 1D carbon allotropes. Analogously, the SW defects behave like a grain boundary that interrupts the consistency of the poly-benzene sections. For a DNT with a fixed length, the yield strength fluctuates in the vicinity of a certain value and is independent of the "grain size". On the other hand, both yield strength and yield strain show a clear dependence on the total length of DNT, which is due to the fact that the failure of the DNT is dominated by the SW defects. Its highly tunable ductility together with its ultra-light density and high Young's modulus makes diamond nanothread ideal for the creation of extremely strong three-dimensional nano-architectures. PMID- 27181832 TI - Accuracy of conization procedure for predicting pathological parameters of radical hysterectomy in stage Ia2-Ib1 (<=2 cm) cervical cancer. AB - The accuracy of conization for the prediction of radical hysterectomy (RH) pathological variables in patients with stage Ia2 to Ib1 (<=2 cm) cervical cancer was retrospectively evaluated in the present study. Endocervical or deep resection margin (RM) involvement in the conization specimens was found to be independently associated with residual disease in the hysterectomy specimens (P < 0.001, = 0.003, respectively). When a tumor width of >20 mm in the final RH pathology analysis was predicted by a tumor width of >2 mm or involvement of endocervical or deep RMs in the conization specimens, the sensitivity and negative predictive value (NPV) of conization were 98.2% and 95.2%, respectively. In addition, when deep stromal invasion in the final RH pathology analysis was predicted by deep stromal invasion or involvement of the endocervical or deep RMs in the conization specimens, the sensitivity and NPV of conization were 98.4% and 95.8%, respectively. The sensitivity and NPV of this prediction model for identifying LVSI in the final RH pathology analysis were both 100%. These findings suggest that conization variables and endocervical and deep resection margin statuses can be analyzed to effectively predict RH pathological parameters. PMID- 27181834 TI - Grasping hydrogen adsorption and dynamics in metal-organic frameworks using (2)H solid-state NMR. AB - Record greenhouse gas emissions have spurred the search for clean energy sources such as hydrogen (H2) fuel cells. Metal-organic frameworks (MOFs) are promising H2 adsorption and storage media, but knowledge of H2 dynamics and adsorption strengths in these materials is lacking. Variable-temperature (VT) (2)H solid state NMR (SSNMR) experiments targeting (2)H2 gas (i.e., D2) shed light on D2 adsorption and dynamics within six representative MOFs: UiO-66, M-MOF-74 (M = Zn, Mg, Ni), and alpha-M3(COOH)6 (M = Mg, Zn). D2 binding is relatively strong in Mg MOF-74, Ni-MOF-74, alpha-Mg3(COOH)6, and alpha-Zn3(COOH)6, giving rise to broad (2)H SSNMR powder patterns. In contrast, D2 adsorption is weaker in UiO-66 and Zn MOF-74, as evidenced by the narrow (2)H resonances that correspond to rapid reorientation of the D2 molecules. Employing (2)H SSNMR experiments in this fashion holds great promise for the correlation of MOF structural features and functional groups/metal centers to H2 dynamics and host-guest interactions. PMID- 27181835 TI - Another Choice for Prevention of COPD Exacerbations. PMID- 27181836 TI - Preparation of ritonavir nanosuspensions by microfluidization using polymeric stabilizers: I. A Design of Experiment approach. AB - The objective of this study was to prepare ritonavir (RTV) nanosuspensions, an anti-HIV protease inhibitor, to solve its poor water solubility issues. The microfluidization method with a pre-treatment step was used to obtain the nanosuspensions. Design of Experiment (DoE) approach was performed in order to understand the effect of the critical formulation parameters which were selected as polymer type (HPMC or PVP), RTV to polymer ratio, and number of passes. Interactions between the formulation variables were evaluated according to Univariate ANOVA. Particle size, particle size distribution and zeta potential were selected as dependent variables. Scanning electron microscopy, X-ray powder diffraction, and differential scanning calorimetry were performed for the in vitro characterization after lyophilization of the optimum nanosuspension formulation. The saturation solubility was examined in comparison with coarse powder, physical mixture and nanosuspension. In vitro dissolution studies were conducted using polyoxyethylene 10 lauryl ether (POE10LE) and biorelevant media (FaSSIF and FeSSIF). The results showed nanosuspensions were partially amorphous and spherically shaped with particle sizes ranging from 400 to 600nm. Moreover, 0.1-0.4 particle size distribution and about -20mV zeta potential values were obtained. The nanosuspension showed a significantly increased solubility when compared to coarse powder (3.5 fold). Coarse powder, physical mixture, nanosuspension and commercial product dissolved completely in POE10LE; however, cumulative dissolved values reached ~20% in FaSSIF for the commercial product and nanosuspension. The nanosuspension showed more than 90% drug dissolved in FeSSIF compared to the commercial product which showed ~50% in the same medium. It was determined that RTV dissolution was increased by nanosuspension formulation. We concluded that DoE approach is useful to develop nanosuspension formulation to improve solubility and dissolution rate of RTV. PMID- 27181837 TI - Evolution of Genome Size in Asexual Digital Organisms. AB - Genome sizes have evolved to vary widely, from 250 bases in viroids to 670 billion bases in some amoebas. This remarkable variation in genome size is the outcome of complex interactions between various evolutionary factors such as mutation rate and population size. While comparative genomics has uncovered how some of these evolutionary factors influence genome size, we still do not understand what drives genome size evolution. Specifically, it is not clear how the primordial mutational processes of base substitutions, insertions, and deletions influence genome size evolution in asexual organisms. Here, we use digital evolution to investigate genome size evolution by tracking genome edits and their fitness effects in real time. In agreement with empirical data, we find that mutation rate is inversely correlated with genome size in asexual populations. We show that at low point mutation rate, insertions are significantly more beneficial than deletions, driving genome expansion and the acquisition of phenotypic complexity. Conversely, the high mutational load experienced at high mutation rates inhibits genome growth, forcing the genomes to compress their genetic information. Our analyses suggest that the inverse relationship between mutation rate and genome size is a result of the tradeoff between evolving phenotypic innovation and limiting the mutational load. PMID- 27181839 TI - Diagnostic performance of swab PCR as an alternative to tissue culture methods for diagnosing infections associated with fracture fixation devices. AB - BACKGROUND: Molecular procedures could potentially improve diagnoses of orthopaedic implant-related infections, but are not yet clinically implemented. Analysis of sonication fluid shows the highest sensitivity for diagnosing implant infections in cases of revision surgery with implant removal. However, there remains controversy regarding the best method for obtaining specimens in cases of revision surgery with implant retention. Tissue culture is the most common diagnostic method for pathogen identification in such cases. Here we aimed to assess the diagnostic performance of swab PCR analysis compared to tissue culture from patients undergoing revision surgery of fracture fixation devices. METHODS: We prospectively investigated 62 consecutive subjects who underwent revision surgery of fracture fixation devices during a two-year period. Tissue samples were collected for cultures, and swabs from the implant surface were obtained for 16S rRNA PCR analysis. Subjects were classified as having an implant-related infection if (1) they presented with a sinus tract or open wound in communication with the implant; or (2) purulence was encountered intraoperatively; or (3) two out of three tissue cultures tested positive for the presence of the same pathogen. Tissue culture and swab PCR results from the subjects were used to calculate the sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and area under the ROC curve (AUC) for identifying an orthopaedic implant-related infection. RESULTS: Orthopaedic implant-related infections were detected in 51 subjects. Tissue culture identified infections in 47 cases, and swab PCR in 35 cases. Among the 11 aseptic cases, tissue culture was positive in 2 cases and swab PCR in 4 cases. Tissue culture showed a significantly higher area under the ROC curve for diagnosing infection (AUC=0.89; 95% CI, 0.67-0.96) compared to swab PCR (AUC=0.66; 95% CI, 0.46-0.80) (p=0.033). CONCLUSIONS: Compared to swab PCR, tissue culture showed better performance for diagnosing orthopaedic implant-related infection. Although molecular methods are expected to yield higher diagnostic accuracy than cultures, it appears that the method of obtaining specimens plays an important role. Improved methods of specimen collection are required before swab PCR can become a reliable alternative to tissue-consumptive methods. PMID- 27181840 TI - A cyclopropene-modified nucleotide for site-specific RNA labeling using genetic alphabet expansion transcription. AB - Site-specific RNA modification with methyl cyclopropene moieties is performed by T7 in vitro transcription. An existing unnatural base is functionalized with a cyclopropene moiety and used in transcription reactions to produce site specifically cyclopropene-modified RNA molecules. The posttranscriptional inverse electron demand Diels-Alder cycloaddition reaction with a selected tetrazine fluorophore conjugate is demonstrated. PMID- 27181841 TI - Wideband Scattering Diffusion by using Diffraction of Periodic Surfaces and Optimized Unit Cell Geometries. AB - A methodology to obtain wideband scattering diffusion based on periodic artificial surfaces is presented. The proposed surfaces provide scattering towards multiple propagation directions across an extremely wide frequency band. They comprise unit cells with an optimized geometry and arranged in a periodic lattice characterized by a repetition period larger than one wavelength which induces the excitation of multiple Floquet harmonics. The geometry of the elementary unit cell is optimized in order to minimize the reflection coefficient of the fundamental Floquet harmonic over a wide frequency band. The optimization of FSS geometry is performed through a genetic algorithm in conjunction with periodic Method of Moments. The design method is verified through full-wave simulations and measurements. The proposed solution guarantees very good performance in terms of bandwidth-thickness ratio and removes the need of a high resolution printing process. PMID- 27181838 TI - PD-L1 polymorphism can predict clinical outcomes of non-small cell lung cancer patients treated with first-line paclitaxel-cisplatin chemotherapy. AB - This study was conducted to investigate whether polymorphisms of genes involved in immune checkpoints can predict the clinical outcomes of patients with advanced stage non-small cell lung cancer (NSCLC) after 1st line paclitaxel-cisplatin chemotherapy. A total of 379 NSCLC patients were enrolled. Twelve single nucleotide polymorphisms (SNPs) of PD-1, PD-L1, and CTLA-4 genes were selected and genotyped. The associations of SNPs with chemotherapy response and overall survival (OS) were analyzed. Among the 12 SNPs investigated, PD-L1 rs2297136T > C and rs4143815C > G were significantly associated with clinical outcomes after chemotherapy. The rs2297136T > C was significantly associated with both better chemotherapy response and better OS, and the rs4143815C > G had a significantly better response to chemotherapy. Consistent with the individual genotype analyses, rs2297136C-rs4143815G haplotype (ht4) carrying variant alleles at both loci was significantly associated with better chemotherapy response and OS compared with combined other haplotypes. Patients with at least one ht4 had significantly better chemotherapy response and OS compared to those without ht4. PD-L1 rs2297136T > C and rs4143815C > G polymorphisms may be useful for the prediction of clinical outcome of 1(st) line paclitaxel-cisplatin chemotherapy in NSCLC. Further studies are needed to confirm our findings and to understand the role of PD-L1 in the chemotherapy outcome of NSCLC patients. PMID- 27181842 TI - Genetic engineering in Actinoplanes sp. SE50/110 - development of an intergeneric conjugation system for the introduction of actinophage-based integrative vectors. AB - The alpha-glucosidase inhibitor acarbose is used for treatment of diabetes mellitus type II, and is manufactured industrially with overproducing derivatives of Actinoplanes sp. SE50/110, reportedly obtained by conventional mutagenesis. Despite of high industrial significance, only limited information exists regarding acarbose metabolism, function and regulation of these processes, due to the absence of proper genetic engineering methods and tools developed for this strain. Here, a basic toolkit for genetic engineering of Actinoplanes sp. SE50/110 was developed, comprising a standardized protocol for a DNA transfer through Escherichia coli-Actinoplanes intergeneric conjugation and applied for the transfer of phiC31, phiBT1 and VWB actinophage-based integrative vectors. Integration sites, occurring once per genome for all vectors, were sequenced and characterized for the first time in Actinoplanes sp. SE50/110. Notably, in case of phiC31 based vector pSET152, the integration site is highly conserved, while for phiBT1 and the VWB based vectors pRT801 and pSOK804, respectively, no sequence similarities to those in other bacteria were detected. The studied plasmids were proven to be stable and neutral with respect to strain morphology and acarbose production, enabling future use for genetic manipulations of Actinoplanes sp. SE50/110. To further broaden the spectrum of available tools, a GUS reporter system, based on the pSET152 derived vector, was also established in Actinoplanes sp. SE50/110. PMID- 27181843 TI - Protective lifestyle behaviours and depression in middle-aged Irish men and women: a secondary analysis. AB - OBJECTIVE: To examine the association between protective lifestyle behaviours (PLB) and depression in middle-aged Irish adults. DESIGN: Secondary analysis of a cross-sectional study. PLB (non-smoker, moderate alcohol, physical activity, adequate fruit and vegetable intake) were assessed using a general health and lifestyle questionnaire and a validated FFQ. Depression was assessed using the Center for Epidemiologic Studies Depression Scale. A score of 15-21 indicates mild/moderate depression and a score of 22 or more indicates a possibility of major depression. Binary logistic regression was used to examine the association between PLB and depression. SETTING: Livinghealth Clinic, Mitchelstown, North Cork, Republic of Ireland. SUBJECTS: Men and women aged 50-69 years were selected at random from a list of patients registered at the clinic (n 2047, 67 % response rate). RESULTS: Over 8 % of participants engaged in zero or one PLB, 24 % and 39 % had two and three PLB respectively, while 28 % had four PLB. Those who practised three/four PLB were significantly more likely to be female, have a higher level of education and were categorised as having no depressive symptoms. Engaging in zero or one PLB was significantly associated with an increased odds of depression compared with four PLB. Results remained significant after adjusting for several confounders, including age, gender, education and BMI (OR=2.2; 95 % CI 1.2, 4.0; P for trend=0.001). CONCLUSIONS: While causal inference cannot be established in a cross-sectional study, the findings suggest that healthy behaviours may play a vital role in the promotion of positive mental health or, at a minimum, are associated with lower levels of depression. PMID- 27181844 TI - Paraventricular Nucleus Modulates Excitatory Cardiovascular Reflexes during Electroacupuncture. AB - The paraventricular nucleus (PVN) regulates sympathetic outflow and blood pressure. Somatic afferent stimulation activates neurons in the hypothalamic PVN. Parvocellular PVN neurons project to sympathoexcitatory cardiovascular regions of the rostral ventrolateral medulla (rVLM). Electroacupuncture (EA) stimulates the median nerve (P5-P6) to modulate sympathoexcitatory responses. We hypothesized that the PVN and its projections to the rVLM participate in the EA-modulation of sympathoexcitatory cardiovascular responses. Cats were anesthetized and ventilated. Heart rate and mean blood pressure were monitored. Application of bradykinin every 10-min on the gallbladder induced consistent pressor reflex responses. Thirty-min of bilateral EA stimulation at acupoints P5-P6 reduced the pressor responses for at least 60-min. Inhibition of the PVN with naloxone reversed the EA-inhibition. Responses of cardiovascular barosensitive rVLM neurons evoked by splanchnic nerve stimulation were reduced by EA and then restored with opioid receptor blockade in the PVN. EA at P5-P6 decreased splanchnic evoked activity of cardiovascular barosensitive PVN neurons that also project directly to the rVLM. PVN neurons labeled with retrograde tracer from rVLM were co-labeled with MU-opioid receptors and juxtaposed to endorphinergic fibers. Thus, the PVN and its projection to rVLM are important in processing acupuncture modulation of elevated blood pressure responses through a PVN opioid mechanism. PMID- 27181846 TI - Data-driven magnetohydrodynamic modelling of a flux-emerging active region leading to solar eruption. AB - Solar eruptions are well-recognized as major drivers of space weather but what causes them remains an open question. Here we show how an eruption is initiated in a non-potential magnetic flux-emerging region using magnetohydrodynamic modelling driven directly by solar magnetograms. Our model simulates the coronal magnetic field following a long-duration quasi-static evolution to its fast eruption. The field morphology resembles a set of extreme ultraviolet images for the whole process. Study of the magnetic field suggests that in this event, the key transition from the pre-eruptive to eruptive state is due to the establishment of a positive feedback between the upward expansion of internal stressed magnetic arcades of new emergence and an external magnetic reconnection which triggers the eruption. Such a nearly realistic simulation of a solar eruption from origin to onset can provide important insight into its cause, and also has the potential for improving space weather modelling. PMID- 27181845 TI - Specific types of alcoholic beverage consumption and risk of type 2 diabetes: A systematic review and meta-analysis. AB - AIMS/INTRODUCTION: Previous meta-analyses identified an inverse association of total alcohol consumption with the risk of type 2 diabetes. The current study further explored the relationship between specific types of alcoholic beverage and the incidence of type 2 diabetes. MATERIALS AND METHODS: A search of PubMed, Embase and Cochrane Library databases from January 1966 to February 2016 was carried out for prospective cohort studies that assessed the effects of specific types of alcoholic beverage on the risk of type 2 diabetes. The pooled relative risks with 95% confidence interval were calculated using random- or fixed-effect models when appropriate. RESULTS: A total of 13 prospective studies were included in this meta-analysis, with 397,296 study participants and 20,641 cases of type 2 diabetes. Relative to no or rare alcohol consumption, wine consumption was associated with a significant reduction of the risk of type 2 diabetes, with the pooled relative risks of 0.85, whereas beer or spirits consumption led to a slight trend of decreasing risk of type 2 diabetes (relative risk 0.96, 0.95, respectively). Further dose-response analysis showed a U-shaped relationship between all three alcohol types and type 2 diabetes. Additionally, the peak risk reduction emerged at 20-30 g/day for wine and beer, and at 7-15 g/day for spirits, with a decrease of 20, 9 and 5%, respectively. CONCLUSIONS: Compared with beer or spirits, wine was associated with a more significant decreased risk of type 2 diabetes. The present study showed that wine might be more helpful for protection against type 2 diabetes than beer or spirits. PMID- 27181871 TI - Transcriptomic responses of the calanoid copepod Calanus finmarchicus to the saxitoxin producing dinoflagellate Alexandrium fundyense. AB - In the Gulf of Maine, the copepod Calanus finmarchicus co-occurs with the neurotoxin-producing dinoflagellate, Alexandrium fundyense. The copepod is resistant to this toxic alga, but little is known about other effects. Gene expression profiles were used to investigate the physiological response of females feeding for two and five days on a control diet or a diet containing either a low or a high dose of A. fundyense. The physiological responses to the two experimental diets were similar, but changed between the time points. At 5 days the response was characterized by down-regulated genes involved in energy metabolism. Detoxification was not a major component of the response. Instead, genes involved in digestion were consistently regulated, suggesting that food assimilation may have been affected. Thus, predicted increases in the frequency of blooms of A. fundyense could affect C. finmarchicus populations by changing the individuals' energy budget and reducing their ability to build lipid reserves. PMID- 27181872 TI - Subcritical Water Processing of Proteins: An Alternative to Enzymatic Digestion? AB - Subcritical water is an emerging tool in the processing of bioorganic waste. Subcritical water is an environmentally benign solvent which has the potential to provide an alternative to traditional methods of protein hydrolysis without the inclusion of expensive acids or enzymes. To date, most studies on the subcritical water mediated hydrolysis of proteins have focused on the production of amino acids, rather than the intermediate peptides. Here, we investigate the specificity of subcritical water with respect to the production of peptides from three model proteins, hemoglobin, bovine serum albumin, and beta-casein, and compare the results with enzymatic digestion of proteins by trypsin. In addition, the effect of subcritical water (SCW) treatment on two protein post-translational modifications, disulfide bonds and phosphorylation, was investigated. The results show that high protein sequence coverages (>80%) can be obtained following subcritical water hydrolysis. These are comparable to those obtained following treatment with tryspin. Under mild subcritical water conditions (160 degrees C), all proteins showed favored cleavage of the Asp-X bond. The results for beta casein revealed favored cleavage of the Glu-X bond at subcritical water temperatures of 160 and 207 degrees C. That was similarly observed for bovine serum albumin at a subcritical water temperature of 207 degrees C. Subcritical water treatment results in very limited cleavage of disulfide bonds. Reduction and alkylation of proteins either prior to or post subcritical water treatment improve reported protein sequence coverages. The results for phosphoprotein beta casein show that, under mild subcritical water conditions, phosphorylation may be retained on the peptide hydrolysis products. PMID- 27181873 TI - Comparison of the effect of bone marrow cells infusion through the portal vein and inferior vena cava combined with short-term rapamycin on allogeneic islet grafts in diabetic rats. AB - AIMS/INTRODUCTION: The study aimed to compare the impact of allogeneic bone marrow cells (BMCs) infusion through the inferior vena cava (IVC) and portal vein (PV) combined with rapamycin on allogeneic islet grafts in diabetic rats. MATERIALS AND METHODS: Recipient diabetic Wistar rats were infused with islets from Sprague-Dawley rats through the PV. PKH26-labeled BMCs of Sprague-Dawley rats were infused to recipients through the PV or IVC, followed by administration of rapamycin for 4 days. Blood glucose level was measured to evaluate the survival time of the islets. Lymphocytes separated from blood, BMCs, thymus, liver, spleen and lymph node were analyzed by flow cytometry. The peripheral blood smear, BMCs smear and frozen sections of tissues were observed by a fluorescence microscope. RESULTS: The survival time of the islets was significantly prolonged by the BMCs infusion combined with rapamycin. The rats receiving BMCs infusion through the PV induced a significantly longer survival time of the islets, and increased mixed chimeras of allogeneic BMCs in the thymus, liver, spleen and lymph node compared with the rats receiving BMCs infusion through the IVC. The amount of the mixed chimeras on day 14 was lower than that on day 7 after islet transplantation. Furthermore, PV transplantation had significantly more mixed chimera than IVC transplantation in all analyzed organs or tissues. CONCLUSIONS: BMCs infusion combined with rapamycin prolongs the islets survival and induces mixed chimeras of BMCs. PV infusion of BMCs might be a more effective strategy than IVC infusion of BMCs. PMID- 27181874 TI - Cardiac rehabilitation delivery model for low-resource settings. AB - OBJECTIVE: Cardiovascular disease is a global epidemic, which is largely preventable. Cardiac rehabilitation (CR) is demonstrated to be cost-effective and efficacious in high-income countries. CR could represent an important approach to mitigate the epidemic of cardiovascular disease in lower-resource settings. The purpose of this consensus statement was to review low-cost approaches to delivering the core components of CR, to propose a testable model of CR which could feasibly be delivered in middle-income countries. METHODS: A literature review regarding delivery of each core CR component, namely: (1) lifestyle risk factor management (ie, physical activity, diet, tobacco and mental health), (2) medical risk factor management (eg, lipid control, blood pressure control), (3) education for self-management and (4) return to work, in low-resource settings was undertaken. Recommendations were developed based on identified articles, using a modified GRADE approach where evidence in a low-resource setting was available, or consensus where evidence was not. RESULTS: Available data on cost of CR delivery in low-resource settings suggests it is not feasible to deliver CR in low-resource settings as is delivered in high-resource ones. Strategies which can be implemented to deliver all of the core CR components in low-resource settings were summarised in practice recommendations, and approaches to patient assessment proffered. It is suggested that CR be adapted by delivery by non physician healthcare workers, in non-clinical settings. CONCLUSIONS: Advocacy to achieve political commitment for broad delivery of adapted CR services in low resource settings is needed. PMID- 27181875 TI - Association of the hypertriglyceridemic waist phenotype and type 2 diabetes mellitus among adults in China. AB - AIMS/INTRODUCTION: To clarify the association of the hypertriglyceridemic waist phenotype and type 2 diabetes mellitus among adults in China. MATERIALS AND METHODS: In the present case-control study, we included 1,685 patients with type 2 diabetes mellitus and 7,141 normal glucose-tolerant controls from the Henan Province of China in 2011. Elevated waist circumference (GW) was defined as >=90 cm for men and >=80 cm for women. Hypertriglyceridemia (HT) was defined as >1.7 m mol/L triglycerides (TG) level. The association of hypertriglyceridemic waist phenotype and type 2 diabetes mellitus was investigated by sex, body mass index, physical activity, and family history of diabetes. RESULTS: Cases and controls differed in age, waist circumference (WC), weight, TG level, fasting glucose, body mass index, smoking status, diabetic family history, physical activity and hypertriglyceridemic waist phenotype (P < 0.05), but not alcohol drinking (P = 0.63). In the overall sample, as compared with the phenotype of normal TG level and normal WC (NTNW), normal TG level/enlarged WC (NTGW), elevated TG level/normal WC (HTNW) and elevated TG level/enlarged WC (HTGW) were associated with type 2 diabetes mellitus (odds ratio 4.14, 2.42 and 6.23, respectively). Only HTGW was consistently associated with risk of type 2 diabetes mellitus, with or without adjustment. The strongest relationship between HTGW and type 2 diabetes mellitus was for subjects with body mass index <24.0 kg/m(2) (odds ratio 6.54, 95% confidence interval 4.22-10.14) after adjustment for cofounding variables. CONCLUSION: HTGW was stably and significantly associated with risk of type 2 diabetes mellitus in adult Chinese. PMID- 27181876 TI - Outcomes related to variation in hospital pulmonary embolus observation stay utilization. AB - OBJECTIVES: To characterize hospital variation in use of observation stays to manage pulmonary embolism (PE) and its association with subsequent outcomes. METHODS: We performed a cross-sectional study of hospitals reporting >=75 PE encounters (emergency department, observation stay or inpatient admission) using Premier data from 11/2012-3/2015. We included hospital encounters for adults with a primary diagnosis of PE (415.1x), >=1 diagnostic test claim for PE on day 0-2 and evidence of PE treatment. Hospitals were divided into tertiles (Ts) based on the proportion of all PE encounters managed as an observation stay. The association between observation stay utilization and the proportion of PE encounters resulting in in-hospital death or re-admission within the same or subsequent 2-months were compared across Ts using a generalized estimating equation adjusted for individual encounter disease severity. RESULTS: Observation PE management increased over the study period (1.9%-5.4%; Pearson's r = 0.88, p < 0.001). Of all hospitals reporting >=1 PE encounter, 255 had >=75 encounters (representing a total of 38,172 PE encounters) and were included in the analysis. Individual hospital observation use for PE management varied from 0%-33.9%. Mean hospital rates of PE observation stay by T were T1 = 0.1%, T2 = 2.2% and T3 = 7.9%. Hospitals that used observation stays most frequently (T3) were more likely in the South or Mid-west (p < 0.001), to be a teaching hospital (p = 0.03) and less likely to serve an urban population (p = 0.02). Hospitals in T3 (n = 11,780 encounters) were not associated with a statistically significant increased risk of in-hospital death (2.3% vs. 2.1%-2.6%) or all-cause (4.7% vs. 5.1%-5.4%), venous thromboembolism-(1.4% vs. 1.8%-2.0%) or major bleeding (0.3% vs. 0.2-0.3%) related re-admission in the same or subsequent 2-months compared to T1 (n = 12,940 encounters) and T2 (n = 13,452 encounters). CONCLUSION: PE management via observation stays has increased over recent years. Hospitals more frequently utilizing observation stays may not experience increased negative outcomes, such as re-admission. PMID- 27181877 TI - Early bone anchorage to micro- and nano-topographically complex implant surfaces in hyperglycemia. AB - The aim of this work was to investigate the effect of implant surface design on early bone anchorage in the presence of hyperglycemia. 108 Wistar rats were separated into euglycemic (EG) controls and STZ-treated hyperglycemic (HG) groups, and received bilateral femoral custom rectangular implants of two surface topographies: grit blasted (GB) and grit-blast with a superimposed calcium phosphate nanotopography (GB-DCD). The peri-implant bone was subjected to a tensile disruption test 5, 7, and 9days post-operatively (n=28/time point); the force was measured; and the residual peri-implant bone was observed by scanning electron microscopy (SEM). Disruption forces at 5days were not significantly different from zero for the GB implants (p=0.24) in either metabolic group; but were for GB+DCD implants in both metabolic groups (p<0.001). Contact osteogenesis was greater on GB-DCD than the GB surface. The nano-and micro-surfaced implants showed significantly different disruption forces at all time points (e.g. >15N and <5N respectively at 9days). Such differences were not seen within the GB implants, as all values were very low (<5N). Even in hyperglycemia the GB-DCD surface outperformed the GB surfaces in both metabolic groups. Significantly, SEM of peri-implant bone showed compromised intra-fibrillar collagen mineralization in hyperglycemia, while inter-fibrillar and cement line mineralization remained unaffected. Enhanced bone anchorage to the implant surfaces was observed on the nanotopographically complex surface independent of metabolic group. The compromised intra-fibrillar mineralization observed provides a mechanism by which early bone mineralization is affected in hyperglycemia. STATEMENT OF SIGNIFICANCE: It is generally accepted that the hyperglycemia associated with diabetes mellitus compromises bone quality, although the mechanism by which this occurs is unknown. Uncontrolled hyperglycemia is therefore a contra-indication for bone implant placement. It is also known that nano-topographically complex implant surfaces accelerate early peri-implant healing. In this report we show that, in our experimental model, nano-topographically complex surfaces can mitigate the compromised bone healing seen in hyperglycemia. Importantly, we also provide a mechanistic explanation for compromised bone quality in hyperglycemia. We show that intra-fibrillar collagen mineralization is compromised in hyperglycemia, but that interfibrillar and cement line mineralization, remain unaffected. PMID- 27181879 TI - Control of silk microsphere formation using polyethylene glycol (PEG). AB - A one step, rapid method to prepare silk microspheres was developed, with particle size controlled by the addition of polyethylene glycol (PEG). PEG molecular weight (4.0K-20.0KDa) and concentration (20-50wt%), as well as silk concentration (5-20wt%), were key factors that determined particle sizes varying in a range of 1-100MUm. Addition of methanol to the PEG-silk combinations increased the content of crystalline beta-sheet in the silk microspheres. To track the distribution and degradation of silk microspheres in vivo, 3 mercaptopropionic acid (MPA)-coated CdTe quantum dots (QDs) were physically entrapped in the silk microspheres. QDs tightly bound to the beta-sheet domains of silk via hydrophobic interactions, with over 96% of the loaded QDs remaining in the silk microspheres after exhaustive extraction. The fluorescence of QDs incorporated silk microspheres less stable in cell culture medium than in phosphate buffer solution (PBS) and water. After subcutaneous injection in mice, microspheres prepared from 20% silk (approx. 30MUm diameter particles) still fluoresced at 24h, while those prepared from 8% silk (approx. 4MUm diameter particles) and free QDs were not detectable, reflecting the QDs quenching and particle size effect on microsphere clearance in vivo. The larger microspheres were more resistant to cell internalization and degradation. Since PEG is an FDA approved polymer, and silk is FDA approved for some medical devices, the methods developed in the present study will be useful in a variety of biomedical applications where simple, rapid and scalable preparation of silk microspheres is required. STATEMENT OF SIGNIFICANCE: The work is of significance to the biomaterial and controlled release society because it provides a new option for fabricating silk microspheres in one simple step of mixing silk and polyethylene glycol (PEG), with the size and properties of microspheres controllable by PEG molecular weight as well as PEG and silk concentrations. Although fabrication of silk microspheres have been reported previously using spray-drying, liposome templating, polyvinyl alcohol (PVA) emulsification, etc., applications were hindered due to harsh conditions (temperature, solvents, etc.) and complicated procedures used as well as low yield and less controllable particle size (usually <10MUm). Since PEG is an FDA-approved polymer, and silk is FDA approved for some medical devices, the methods developed in the present study will be useful in a variety of biomedical applications where simple, rapid and scalable preparation of silk microspheres is required. PMID- 27181880 TI - Biofunctionalization of PEDOT films with laminin-derived peptides. AB - Poly(3,4-ethylenedioxythiophenes) (PEDOT) have been extensively explored as materials for biomedical implants such as biosensors, tissue engineering scaffolds and microelectronic devices. Considerable effort has been made to incorporate biologically active molecules into the conducting polymer films in order to improve their long term performance at the soft tissue interface of devices, and the development of functionalized conducting polymers that can be modified with biomolecules would offer important options for device improvement. Here we report surface modification, via straightforward protocols, of carboxylic acid-functional PEDOT copolymer films with the nonapeptide, CDPGYIGSR, derived from the basement membrane protein laminin. Evaluation of the modified surfaces via XPS and toluidine blue O assay confirmed the presence of the peptide on the surface and electrochemical analysis demonstrated unaltered properties of the peptide-modified films. The efficacy of the peptide, along with the impact of a spacer molecule, for cell adhesion and differentiation was tested in cell culture assays employing the rat pheochromocytoma (PC12) cell line. Peptide-modified films comprising the longest poly(ethylene glycol) (PEG) spacer used in this study, a PEG with ten ethylene glycol repeats, demonstrated the best attachment and neurite outgrowth compared to films with peptides alone or those with a PEG spacer comprising three ethylene glycol units. The films with PEG10-CDPGYISGR covalently modified to the surface demonstrated 11.5% neurite expression with a mean neurite length of 90MUm. This peptide immobilization technique provides an effective approach to biofunctionalize conducting polymer films. STATEMENT OF SIGNIFICANCE: For enhanced diagnosis and treatment, electronic devices that interface with living tissue with minimum shortcomings are critical. Towards these ends, conducting polymers have proven to be excellent materials for electrode-tissue interface for a variety of biomedical devices ranging from deep brain stimulators, cochlear implants, and microfabricated cortical electrodes. To improve the electrode-tissue interface, one strategy utilized by many researchers is incorporating relevant biological molecules within or on the conducting polymer thin films to provide a surface for cell attachment and/or provide biological cues for cell growth. The present study provides a facile means for generating PEDOT films grafted with a laminin peptide with or without a spacer molecule for enhanced cell attachment and neurite extension. PMID- 27181881 TI - Can restoring immune balance be the ultimate therapy for type 1 diabetes? PMID- 27181878 TI - Human iPSC-derived endothelial cell sprouting assay in synthetic hydrogel arrays. AB - Activation of vascular endothelial cells (ECs) by growth factors initiates a cascade of events during angiogenesis in vivo consisting of EC tip cell selection, sprout formation, EC stalk cell proliferation, and ultimately vascular stabilization by support cells. Although EC functional assays can recapitulate one or more aspects of angiogenesis in vitro, they are often limited by undefined substrates and lack of dependence on key angiogenic signaling axes. Here, we designed and characterized a chemically-defined model of endothelial sprouting behavior in vitro using human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs). We rapidly encapsulated iPSC-ECs at high density in poly(ethylene glycol) (PEG) hydrogel spheres using thiol-ene chemistry and subsequently encapsulated cell-dense hydrogel spheres in a cell-free hydrogel layer. The hydrogel sprouting array supported pro-angiogenic phenotype of iPSC ECs and supported growth factor-dependent proliferation and sprouting behavior. iPSC-ECs in the sprouting model responded appropriately to several reference pharmacological angiogenesis inhibitors of vascular endothelial growth factor, NF kappaB, matrix metalloproteinase-2/9, protein kinase activity, and beta-tubulin, which confirms their functional role in endothelial sprouting. A blinded screen of 38 putative vascular disrupting compounds from the US Environmental Protection Agency's ToxCast library identified six compounds that inhibited iPSC-EC sprouting and five compounds that were overtly cytotoxic to iPSC-ECs at a single concentration. The chemically-defined iPSC-EC sprouting model (iSM) is thus amenable to enhanced-throughput screening of small molecular libraries for effects on angiogenic sprouting and iPSC-EC toxicity assessment. STATEMENT OF SIGNIFICANCE: Angiogenesis assays that are commonly used for drug screening and toxicity assessment applications typically utilize natural substrates like Matrigel(TM) that are difficult to spatially pattern, costly, ill-defined, and may exhibit lot-to-lot variability. Herein, we describe a novel angiogenic sprouting assay using chemically-defined, bioinert poly(ethylene glycol) hydrogels functionalized with biomimetic peptides to promote cell attachment and degradation in a reproducible format that may mitigate the need for natural substrates. The quantitative assay of angiogenic sprouting here enables precise control over the initial conditions and can be formulated into arrays for screening. The sprouting assay here was dependent on key angiogenic signaling axes in a screen of angiogenesis inhibitors and a blinded screen of putative vascular disrupting compounds from the US-EPA. PMID- 27181882 TI - Evidence of weak localization in quantum interference effects observed in epitaxial La0.7Sr0.3MnO3 ultrathin films. AB - Quantum interference effects (QIEs) dominate the appearance of low-temperature resistivity minimum in colossal magnetoresistance manganites. The T(1/2) dependent resistivity under high magnetic field has been evidenced as electron electron (e-e) interaction. However, the evidence of the other source of QIEs, weak localization (WL), still remains insufficient in manganites. Here we report on the direct experimental evidence of WL in QIEs observed in the single-crystal La0.7Sr0.3MnO3 (LSMO) ultrathin films deposited by laser molecular beam epitaxy. The sharp cusps around zero magnetic field in magnetoresistance measurements is unambiguously observed, which corresponds to the WL effect. This convincingly leads to the solid conclusion that the resistivity minima at low temperatures in single-crystal manganites are attributed to both the e-e interaction and the WL effect. Moreover, the temperature-dependent phase-coherence length corroborates the WL effect of LSMO ultrathin films is within a two-dimensional localization theory. PMID- 27181884 TI - High-normal blood pressure is associated with visit-to-visit blood pressure variability in the US adults. AB - OBJECTIVES: High-normal blood pressure and visit-to-visit blood pressure variability are common in clinical settings. They are associated with cardiovascular outcomes. No population based studies have assessed the association between these two phenomena. Our objective was to test the relationship of high-normal blood pressure with visit-to-visit blood pressure variability. DESIGN: A cross-sectional study. METHODS: We used data from the cross-sectional Third National Health and Nutrition Examination Survey to test the relationship between high-normal blood pressure and visit-to-visit blood pressure variability; we conducted multivariable regression analyses to evaluate the relationship between these two variables. RESULTS: The analysis included 6,071 participants. The participants' mean age was 37.16 years. The means of visit-to-visit systolic and diastolic blood pressure variability were 5.84 mmHg and 5.26 mmHg. High-normal blood pressure was significantly associated with systolic and diastolic blood pressure variability (p values <0.05). CONCLUSIONS: High-normal blood pressure is associated with visit-to-visit blood pressure variability. Additional research is required to replicate the reported results in prospective studies and evaluate approaches to reduce blood pressure variability observed in clinical settings among patients with high-normal blood pressure to reduce the subsequent complications of blood pressure variability. PMID- 27181883 TI - Neural representation of scene boundaries. AB - Three-dimensional environmental boundaries fundamentally define the limits of a given space. A body of research employing a variety of methods points to their importance as cues in navigation. However, little is known about the nature of the representation of scene boundaries by high-level scene cortices in the human brain (namely, the parahippocampal place area (PPA) and retrosplenial complex (RSC)). Here we use univariate and multivoxel pattern analysis to study classification performance for artificial scene images that vary in degree of vertical boundary structure (a flat 2D boundary, a very slight addition of 3D boundary, or full walls). Our findings present evidence that there are distinct neural components for representing two different aspects of boundaries: 1) acute sensitivity to the presence of grounded 3D vertical structure, represented by the PPA, and 2) whether a boundary introduces a significant impediment to the viewer's potential navigation within a space, represented by RSC. PMID- 27181885 TI - GLS-Finder: A Platform for Fast Profiling of Glucosinolates in Brassica Vegetables. AB - Mass spectrometry combined with related tandem techniques has become the most popular method for plant secondary metabolite characterization. We introduce a new strategy based on in-database searching, mass fragmentation behavior study, formula predicting for fast profiling of glucosinolates, a class of important compounds in brassica vegetables. A MATLAB script-based expert system computer program, "GLS-Finder", was developed. It is capable of qualitative and semi quantitative analyses of glucosinolates in samples using data generated by ultrahigh-performance liquid chromatography-high-resolution accurate mass with multi-stage mass fragmentation (UHPLC-HRAM/MS(n)). A suite of bioinformatic tools was integrated into the "GLS-Finder" to perform raw data deconvolution, peak alignment, glucosinolate putative assignments, semi-quantitation, and unsupervised principal component analysis (PCA). GLS-Finder was successfully applied to identify intact glucosinolates in 49 commonly consumed Brassica vegetable samples in the United States. It is believed that this work introduces a new way of fast data processing and interpretation for qualitative and quantitative analyses of glucosinolates, where great efficacy was improved in comparison to identification manually. PMID- 27181886 TI - [Comparison of the Effectiveness of Different Supraglottic Ventilation Methods during Bronchial Thermoplasty]. AB - OBJECTIVE: To compare the effectiveness of high-frequency jet ventilation via Wei jet nasal airway and controlled ventilation with improved laryngeal mask airway during bronchial thermoplasty. METHODS: Twenty-eight patients undergoing bronchial thermoplasty were equally divided into two groups: group A (high frequency jet ventilation through Wei jet nasal airway) and group B (controlled ventilation with improved laryngeal mask airway). Pulse oxygenation,heart rate,and mean arterial blood pressure were recorded after entering the operating room (T0), 1 minute after administration/induction (T1), bronchoscope inserting (T2), 15 minutes (T3)/30 minutes (T4)/45 minutes (T5) after ventilation,at the end of the operation (T6), and at the recovery of patients' consciousness (T7). The pH,arterial oxygen partial pressure,and arterial carbon dioxide partial pressure were recorded at T0, T4, and T6. The endoscope indwelling duration,operative time,patients' awakening time,adverse events during anesthesia,satisfactions of patients and operators, anesthesic effectiveness were also recorded. RESULTS: The arterial carbon dioxide partial pressur in group A at T4 and T6 were significantly higher than in group B (P<0.05). The pH in group A at T4 and T6 was significantly lower than in group B (P<0.05). The endoscope indwelling duration and the operative time in group B were significantly shorter than in group A (P<0.05) while the recovery of consciousness in group B was significantly longer than in group A (P<0.05). The satisfaction for operators and the efficacy of anesthesia in group B were better than in group A (P<0.05). The number of adverse events in group B was significantly smaller than in group A (P<0.05). CONCLUSION: The improved laryngeal mask airway with controlled ventilation is more suitable for bronchial thermoplasty. PMID- 27181887 TI - [Audiological and Otological Status of 45 Infants with Cleft Palate]. AB - OBJECTIVE: To study the audiological and otological status of cleft palate infants with the application of distortion product otoacoustic emission (DPOAE), auditory brainstem response (ABR), tympanometry with 1000 Hz and 226 Hz probe tones. METHODS: Totally 45 cleft palate infants aged 8-24 months were included in the study. Most of them were examined for DPOAE, ABR and two frequency tympanometry. RESULTS: Most infants failed the three tests,among whom 6.7% ears passed DPOAE and 33.3% of ears had normal ABR hearing threshold. In addition, 8.9% of ears turned out normal in the 1000 Hz probe-tone tympanometry, and 13.3% were type A in the 226 Hz probe-tone tympanometry. Finally, 1000 Hz tympanometry had more agreement with DPOAE and latency of ABR wave I than 226 Hz tympanometry. CONCLUSION: Most cleft palate infants have audiological and otological problems, which should be evaluated in a more comprehensive manner. PMID- 27181888 TI - [Effect of Paroxysmal Atrial Fibrillation on Parameters Monitored by Transpulmonary Thermodilution Method]. AB - OBJECTIVE: To investigate the effect of atrial fibrillation on the accuracy of parameters monitored by transpulmonary thermodilution method. METHODS: Totally 12 patients from emergency intensive care unit with paroxysmal atrial fibrillation were enrolled. The hemodynamic parameters such as heart rate, mean arterial pressure, cardiac index, systemic vascular resistance index, intrathoracic blood volume index, and extravascular lung water index were monitored by transpulmonary thermodilution method before paroxysmal atrial fibrillation and during atrial fibrillation, the number of B-lines was detected by lung ultrasonography before and during paroxysmal atrial fibrillation. The changes of all the parameters were analyzed. RESULTS: When the paroxysmal atrial fibrillation happened, the heart rate increased significantly [(123.3+/-20.0) beat/min vs. (98.9+/-12.3) beat/min, P=0.006]; the mean arterial pressure [(86.9+/-10.2) mmHg vs. (93.0+/-12.5) mmHg, P=0.058], cardiac index [(2.82+/-0.62) L/(min.m(2)) vs. (3.31+/-1.02) L/(min.m(2)), P=0.058] and systemic vascular resistance index [(2254+/-947) dyn.s.cm(-5).m(2) vs. (2302+/-828) dyn.s.cm(-5).m(2), P=0.351] had no obvious change; however, the intrathoracic blood volume index significantly increased [(1333+/-90) ml/m(2) vs. (937+/-111) ml/m(2), P<0.001]; extravascular lung water index also increased significantly [(16.1+/-1.1) ml/kg vs. (6.5+/-1.9) ml/kg, P<0.001]. No significant difference was found in the number of B-lines detected by lung ultrasonography before and during atrial fibrillation (10.0+/-4.2 vs. 9.4+/-4.4, P=0.180). CONCLUSION: Both intrathoracic blood volume and extravascular lung water monitored by transpulmonary thermodilution method were overvalued during paroxysmal atrial fibrillation, which may mislead the clinical judgment and decision-making. PMID- 27181889 TI - [Roles of MicroRNA-21 in the Pathogenesis of Insulin Resistance and Diabetic Mellitus-induced Non-alcoholic Fatty Liver Disease]. AB - OBJECTIVE: To investigate the roles of microRNA-21 (miR-21) in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) with high-fat diet-induced insulin resistance (IR) and diabetes mellitus (DM) mice model. METHODS: Eight-week-old C57BL/6 mice were allocated into control group, IR group, and DM group. Body mass was recorded. Intraperitoneal glucose tolerance test was performed to determine any abnormal glucose metabolism. The liver pathological changes were detected by biopsy. Changes in free blood glucose, free serum insulin, blood fat and tumor necrosis factor Alpha level were measured. Differences in miR-21 expression and peroxidase proliferator-activated receptor subtypes (PPAR-Gamma and PPAR-Alpha) and adipocyte fatty acid binding protein (aP2) in the liver were detected both at the mRNA and protein levels. RESULTS: After one 8-week high-fat diet, the body mass, free serum insulin, and homeostasis model IR index significantly increased in the IR group (P<0.01, P<0.05, compared with control group), while the free blood glucose increased and the free serum insulin decreased in DM group (P<0.05). Free serum insulin level were significantly increased in IR group (P<0.05). Serum tumor necrosis factor-Alpha levels exhibited an upward trend in control group, IR group, and DM group (P<0.05, P<0.01). With exacerbation in NAFLD, liver miR-21 expression level went further down in both IR and DM groups (P<0.05). The downregulated miR-21 expression level showed negative correlation with upregulated PPAR-Alpha, AlphaP2, and PPAR-Gamma genetic expression (r= 0.696, r=-0.664, and r=-0.766, respectively; P<0.05) in IR group and with upregulated PPAR-Alpha and PPAR-Gamma genetic expression in DM group (r=-0.676 and r=-0.550, respectively; P<0.05). In terms of the changes in protein expression level,only on the protein expressions of aP2 and PPAR-Gamma in IR group showed significant change (P<0.05, P<0.01, compared with control group). CONCLUSIONS: The miR-21 expression is downregulated in both IR and DM-induced NAFLD mice. It may be involved in the pathogenesis of NAFLD by regulating the expressions of PPAR subtypes. PMID- 27181890 TI - [Change of Serum Angiopoietin-related Growth Factor in Patients with Abdominal Aortic Aneurysm and Its Clinical Significance]. AB - OBJECTIVE: To investigate the changes and value of plasma angiopoietin-related growth factor (AGF) in patients with abdominal aortic aneurysm (AAA). METHODS: Serum AGF level was analyzed in 50 AAA patients and in 56 healthy subjects. AGF and adiponectin were quantified by enzyme-linked immunosorbent assay. Routine testing of blood biochemistry and high-sensitivity C-reactive protein were performed. RESULTS: The plasma AGF level was significantly higher in AAA patients than in the controls [(87.91+/-96.87) MUg/L vs. (56.89+/-41.32) MUg/L, P=0.040],while serum adiponectin level showed no significant difference between these two groups. The plasma AGF level in patients with an AAA>5 cm and those with AAA between 3 cm and 5 cm were (96.08+/-68.61) MUg/L and (75.27+/-46.05) MUg/L. CONCLUSIONS: Plasma AGF is highly expressed in AAA patients. Higher serum AGF level is associates with larger AAA. Thus, AGF may be a potential serum biomarker for AAA. PMID- 27181891 TI - [Effect and Regulatory Mechanism of Clock Gene Per1 on Biological Behaviors of Human Oral Squamous Carcinoma Cell]. AB - OBJECTIVE: To investigate the effect and regulatory mechanism of clock gene Per1 on the proliferation,apoptosis,migration,and invasion of human oral squamous carcinoma SCC15 cells. METHODS: RNA interference was used to knock down Per1 gene in human oral squamous cell carcinoma SCC15 cell line. Changes of cell proliferation and apoptosis were analyzed by flow cytometry. Transwell assay was carried out to assess cell migration and invasion. Real-time polymerase chain reaction was used to detect the mRNA expressions of Ki-67, murine double minute 2 (MDM2), c-Myc, p53, Bax, Bcl-2, metalloproteinase (MMP)2, MMP9, and vascular endothelial growth factor (VEGF). RESULTS: shRNA-mediated knockdown of Per1 promoted the proliferation, migration and invasion capacity, and inhibited cell apoptosis capacity of SCC15 cells (all P<0.05). Additionally, Per1 knockdown also increased the mRNA expressions of Ki-67, MDM2, Bcl-2, MMP2, and MMP9 and decreased the mRNA expressions of c-Myc, p53, and Bax (all P<0.05); however, the VEGF mRNA expression did not differ significantly after Per1 knockdown (P>0.05). CONCLUSIONS: Clock gene Perl can regulate important tumor-related genes downstream such as Ki-67, MDM2, c-Myc, p53, Bax, Bcl-2, MMP2, and MMP9, and the aberrant expression of Per1 can affect tumor cell proliferation,apoptosis,migration and invasion. An in-depth study of Per1 may further clarify the mechanism of tumorigenesis and tumor development and thus provides new effective molecular targets for cancer treatment. PMID- 27181892 TI - [Human Umbilical Cord-derived Mesenchymal Stem Cells Secrete Interleukin-6 to Influence Differentiation of Leukemic Cells]. AB - OBJECTIVE: To investigate the effect of human umbilical cord-derived mesenchymal stem cells (UC-MSC) on the differentiation of leukemic cells. METHODS: The co culture system of UC-MSC with acute promyelocytic leukemic cell line NB4 cells was constructed in vitro,and the differentiation status of the leukemic cells was assessed by cell morphology,nitroblue tetrazolium reduction test,and cell surface differentiation marker CD11b. RESULTS: UC-MSC induced the granulocytic differentiation of NB4 cells. When UC-MSC and a small dose of all-trans retinoic acid were applied together,the differentiation-inducing effect was enhanced in an additive manner. Interleukin (IL)-6Ra neutralization attenuated differentiation and exogenous IL-6-induced differentiation of leukemic cells. CONCLUSION: UC-MSC can promotd granulocytic differentiation of acute promyelocytic leukemia cells by way of IL-6 and presented additive effect when combined with a small dose of all trans retinoic acid. PMID- 27181893 TI - [Relationship between P53 Protein Expression and Prognosis of Advanced Ovarian Serous Adenocarcinoma]. AB - OBJECTIVE: To study the expression of P53 protein in the advanced ovarian serous adenocarcinoma and explore its potential correlation with the clinicopathological features and prognosis of ovarian cancer. METHODS: The immunohistochemical staining was used to detect the expression of P53 protein in 183 patients with advanced ovarian serous adenocarcinoma. The correlation of P53 protein with the clinicopathological features and its significance in the assessment of prognosis were explored. RESULTS: The P53 protein expression was positive in 62.8% of the patients. Chi-square test showed that the overexpression of P53 protein was positively correlated with the elevation of serum CA125 and the two-tier grading of ovarian serous adenocarcinoma (P<0.001, P=0.038). Univariate analysis suggested that the prognosis of patients was associated with two-tier grading (P=0.007), lymph node metastasis (P=0.036), preoperative serum CA125 level (P=0.002), and P53 overexpression (P<0.001). Multivariate analysis showed that the International Federation of Gynecology and Obstetrics stage (P=0.038), lymph node metastasis (P=0.002), and overexpression of P53 (P=0.001) were independent prognostic factors. CONCLUSION: The P53 protein expression is closely related to the prognosis of advanced ovarian serous adenocarcinoma and can be used as an important indicator for predicting the prognosis. PMID- 27181894 TI - [Comparison of the Predictive Values of Eight Staging Systems for Primary Liver Cancer in Prognosis of Combined Hepatocellular-cholangiocellular Carcinoma Patients after Surgery]. AB - OBJECTIVE: To compare the predictive values of eight staging systems for primary liver cancer in the prognosis of combined hepatocellular-cholangiocellular carcinoma (cHCC-CC) patients after surgery. METHODS: The clinical data of 54 cHCC CC patients who underwent hepatectomy or liver transplantation from May 2005 to Augest 2013 in Chinese PLA General Hospital were collected. We evaluated the prognostic value of the Okuda staging system, Cancer of the Liver Italian Program (CLIP) score, French staging system, Barcelona Clinic Liver Cancer (BCLC) staging system, 7th edition of tumour-node-metastasis (TNM) staging system for hepatocellular carcinoma and intrahepatic cholangiocarcinoma (ICC), Japan Integrated Staging (JIS) score, and Chinese University Prognostic Index. The distribution, Kaplan-Meier method, Log-rank test, and area under a receiver operating characteristic curve were used to compare the prognosis-predicting ability of these different staging systems in 54 cHCC-CC patients after surgery. RESULTS: The TNM staging system for ICC and JIS score had a better distribution of cases. The 12-and 24-month survivals of the entire cohort were 65.5% and 56.3%, respectively. A Log-rank test showed that there was a significant difference existing in the cumulative survival rates of different stage patients when using TNM staging system for ICC (stage 1 vs. stage 2, P=0.012; stage 2 vs. stage 3-4, P=0.002), Okuda staging system (stage 1 vs. stage 2, P=0.025), and French staging system (stage A and stage B, P=0.045). The 12-and 24-month area under curve of TNM staging system for ICC, BCLC staging system, JIS score, and CLIP score were 0.836 and 0.847, 0.744 and 0.780, 0.723 and 0.764, and 0.710 and 0.786, respectively. CONCLUSION: The 7th edition of TNM staging system for ICC has superior prognostic value to other seven staging systems in cHCC-CC patients undergoing surgical treatment. PMID- 27181896 TI - [Effect of Postpartum Depression on Adolescent Depression of Mice Offspring]. AB - OBJECTIVE: To study the effect of postpartum depression (PPD) on adolescent depression of mice offspring. METHODS: Totally 48 Balb/c female mice were equally randomized into control group and stress group. Control group was not given any stress, whereas stress group were given chronic stress: constraining (6 h/d) combined with light stimulation for 24 hours (twice a week). The stress group was divided into 3 groups to measue the animals' behaviors immediately after modeling, three weeks after modeling, and three weeks after delivery to test whether the PPD models were successfully constructed. The first generation (F1) of normal mothers and PPD-born F1 were as follows: control group (CTL-F1) and PPD offspring group (PPD-F1). The 3-4-week-old male CTL-F1 and PPD-F1 mice (n=8 each) were weighed, and received sucrose preference test, forced swimming test, and novelty-supressed feeding test to measure the depression-like behaviors. RESULTS: The 3-and 4-week-old PPD-F1 had significantly lower body mass than CTL-F1 (P=0.000, P=0.002). Also, the sucrose preference significantly decreased (P=0.000), the forced swimming immobility time significantly increased (P=0.001), the latency to feed significantly increased (P=0.000), while food intake significantly decreased (P=0.005). CONCLUSION: PPD offspring may be more susceptible to depression,with a possible eary onset in adolescence. PMID- 27181895 TI - [Correlations between Vessel Changes and the Histopathologic Subtypes of Lung Adenocarcinoma with Pure Ground-glass Nodule on Computed Tomography]. AB - OBJECTIVE: To investigate the correlations between vessel changes and the histopathologic subtypes of lung adenocarcinoma with pure ground-glass nodule (pGGN) on computed tomography (CT). METHODS: Totally 107 patients (116 lesions) with lung adenocarcinomas with pGGN who had undergone curative resection were included. Vessel changes included vascular convergence and/or vessel dilation or distortion within the pGGN. According to the vessel appearances within the pGGN, all patients were categorized into two groups: no change group and change group. Pearson chi-square test was used to analyze the relationships between vessel changes and histopathologic subtypes. Mann-Whitney rank test and t-test were used to identify the relationship of vessels changes with pGGN density and diameter. RESULTS: Among these 116 pGGNs, there were 21 without vessel changes and 4 with vessel changes in 25 preinvasive lesions; 14 without vessel changes and 15 with vessel changes in 29 minimally invasive adenocacinomas; 16 without vessel changes and 46 with vessel changes in 62 invasive lung adenocarcinomas. There were statistically significant differences of vessel changes (P=0.000) among histopathologic subtypes. The lesion diameter was significantly different between these two groups (P=0.000), while the lesion density showed no significant difference (P=0.826). CONCLUSION: Vessel changes may indicate the invasiveness of lung adenocarcinoma with pGGNs and are related with the lesion diameter. PMID- 27181898 TI - [Construction of Nude Mouse Model of Triple Negative Breast Cancer and Value of Thermal Tomography]. AB - OBJECTIVE: To explore the early detection of breast cancer by ultrasonic imaging and thermal tomography of luciferase or green fluorescent protein (GFP)-labeled MDA-MB-231 breast cancer cell line-xenografts in nude mice. METHODS: Fluorescence tagged lentiviral vectors were transfected into the triple-negative breast cancer cell line MDA-MB-231. These cells were implanted either subcutaneously under the right breast pad or intravenously into the tail vein of nude BALB/C mice. Thermal tomography and ultrasound imaging were used to detect tumor formation and to monitor tumor growth and metastasis in vivo. RESULTS: Triple negative breast cancer cell line-xenografts were used to successfully construct an orthotopic nude mice model of breast cancer metastasis in the peritoneum. Thermal tomography and ultrasound imaging were used together to detect small tumors. Thermal tomography imaging detected small tumors earlier than ultrasound imaging. CONCLUSIONS: Thermal tomography can be used to monitor changes in tumor growth and detect abnormal tissue. Therefore, it can serve as a convenient,rapid,sensitive, and reliable technique for early screening of human breast cancer. PMID- 27181897 TI - [Association of Insulin Resistance and beta Cell Function with Lipid Metabolism in Middle-aged and Elderly Hui and Han Populations]. AB - OBJECTIVE: To explore the association of insulin resistance and beta cell function with lipid metabolism in middle-aged and elderly Hui and Han populations. METHODS: A total of 1000 subjects age over 40 years were recruited from five urban communities in Yinchuan and Wuzhong cities of Ningxia. The composition ratio between Hui and Han nationality was 1:2. A questionnaire-based survey was performed. Physical examinations were carried out to measure the height, body mass, waistline, and hipline. The levels of triglyceride (TG), total cholesterol (TC), blood uric acid (BUA), fasting blood glucose and insulin were measured. The boby mass index (BMI), waist-hip ratio (WHR), and secretion related index including insulin resistance index (IR), insulin sensitivity index (IAI), and beta cell function index (HBCI) were calculated. RESULTS: The BMI, WHR, IAI, HBCI, and the prevalence rate of diabetes in Hui nationality were significantly higher than those in Han nationality (P<0.01). The levels of BUA, fasting blood glucose, TC, and IR in Han nationality were significantly lower than those in Hui nationality (P<0.01). In Hui populations, TG, BMI, WHR, and BUA were positively correlated with IR (r=0.234, r=0.193, r=0.143, and r=0.129, respectively; P<0.01) and were negatively correlated with IAI (r=-0.234, r=-0.193, r=-0.143, r=-0.129, respectively; P<0.01), whereas TC was negatively correlated with HBCI (r=-0.169, P<0.01). In Han populations, TC, TG, BMI, WHR, and BUA were positively correlated with IR (r=0.140, r=0.257, r=0.288, r=0.163, r=0.104, P<0.01) and negatively correlated with IAI (r=-0.140, r=-0.257, r=-0.288, r=-0.163, and r=-0.104, P<0.01), whereas BMI was negatively correlated with HBCI (r=-0.111, P<0.01). After the influential factors such as gender, nationality, and age were adjusted, the TC, TG, BMI, WHR, BUA levels were positively correlated with IR (r=0.109, r=0.256, r=0.253, r=0.139, and r=0.142, P<0.01) and negatively correlated with IAI (r=-0.109, r=-0.256, r=-0.253, r=-0.139, and r=-0.142, P<0.01). TC and BMI were negatively correlated with HBCI (r=-0.113, r=-0.086, P<0.01). TG and BMI were independently associated with IR and IAI (r=0.218, r=0.182, r=-0.218, r= 0.182), while TC and BMI were independently associated with HBCI (r=-0.113, r= 0.086). CONCLUSIONS: The distributions of TC, TG, BMI, WHR, BUA, IR, IAI, and HBCI differ between Han and Hui populations. The development of insulin resistance is closely related with the increased levels of TC, TG, BMI, WHR, and BUA. However, the HBCI increases with the increased level of TC and BMI. TG and BMI may be related with insulin resistance. Also, TC and BMI may affect the secretion function of beta cells. PMID- 27181899 TI - [Expression Patterns of the Proteins Associated with Cell Junctions in Mouse Testes]. AB - OBJECTIVE: To study on the expression patterns of proteins associated with cell junctions in the developing mouse testes. METHOD: The expression levels of reproductive related cell lines spermatogonia cell line GC1 spg, spermatocyte cell line GC2 spg, leydig cell line TM3, and sertoli cell line TM4, primary sertoli cells, and 1-6-week mouse testes were analyzed using Western blot. RESULTS: The sertoli cell junction-associated membrane proteins adhesion molecule A, Occludin and Claudin, and the sertoli-germ cell junction-associated membrane proteins junctional adhesion molecule C, Nectin-3, and E-cadherin were stage specific in the seminiferous tubules in the mouse testes. The adaptor proteins associated with cell juctions zonula occludens-1, zonula occludens-2, Afadin, Beta-catenin, and CD2-associated protein were not stage-specific in the seminiferous tubules in the mouse testes. CONCLUSIONS: In the seminiferous tubules in the mouse testes, the membrane proteins associated with cell junctions are stage-specific. However, the expressions of adaptor proteins associated with cell junctions do not obviously change. PMID- 27181900 TI - [An Analysis on the Association between Lipid Metabolism and Low Birth Body Mass and Relative Factors among Rural and Urban Adolescents]. AB - OBJECTIVE: To analyze the status of lipid metabolism and the relationship between low birth body mass and lipid metabolism disorders in adolescents with different economic and cultural backgrounds. METHODS: Totally 1700 adolescents from urban and rural areas aged 12-18 years were selected in 2013. The lipid profiles were determined, and a questionnaire-based survey was conducted. RESULTS: Among normal birth body mass adolescents, girls obtained a high density lipoprotein in both urban and rural areas, low density lipoprotein cholesterol level was higher for city girls, rural boys and urban girls obtained higher total cholesterol level, the differences all reached statistical significance. While among the low birth body mass adolescents, higher level of total cholesterol for urban boys was detected, with statistically significance. When compared between rural and urban areas, high density lipoprotein cholesterol level for urban adolescents was lower in normal birth body mass adolescents, while total cholesterol level for urban adolescents was higher, both with statistically significance. While the comparison between different birth body mass adolescents suggested that the normal birth body mass adolescents obtained a higher high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglyceride and total cholesterol level. When analyze the influenced factors of disorder of lipid metabolism, the Results suggest that low birth body mass, maternal pregnancy body mass increasing, lipid homeostasis family history, absence of breakfast, unhealthy snack habit, abnormal of systolic blood pressure and pulse pressure increasing were related to the occurrence of dyslipidemia. CONCLUSIONS: Low birth body mass is related with lipid metabolism in early puberty. Low birth body mass, family history of abnormal lipid metabolism, and poor diet habits can increase the risk of abnormal lipid metabolism in puberty. PMID- 27181901 TI - [Impacts of Erythropoietin on Vascular Endothelial Growth Factor Receptor 2 by the Extracellular Signal-regulated Kinase Signaling Pathway in a Neonatal Rat Model of Periventricular White Matter Damage]. AB - OBJECTIVE: To explore the impacts of erythropoietin on vascular endothelial growth factor receptor 2 (VEGFR2) by the extracellular signal-regulated kinase (ERK) signaling pathway in a neonatal rat model of periventricular white matter damage. METHODS: All of postnatal day 4 rats were randomized into three groups: the sham group [without hypoxia-ischemia (HI)], the HI group (HI with saline administration), and the erythropoietin (EPO) group [HI with recombinant human erythropoietin (rh-EPO) administration]. Rat pups underwent permanent ligation of the right common carotid artery, followed by 6% O2 for 2 hours or sham operation and normoxic exposure. Immediately after the HI, rats received a single intraventricular injection of rh-EPO (0.6 IU/g body mass) or saline. ERK and phosphorylation-ERK were examined at 60 minutes and 90 minutes after operation, and VEGFR2 were detected at 2 and 4 days after operation by using Western blot. RESULTS: At 60 minutes and 90 minutes after operation, the proteins of phosphorylation-ERK were significantly higher in HI rats than in the sham rats and significantly higher in HI+EPO rats than in the HI rats (P<0.05). Two days after operation, VEGFR2 was not significantly different between sham and HI rats. However, the proteins of VEGFR2 were increased after administration of rh-EPO (P<0.05). Four days after operation, the proteins of VEGFR2 were significantly higher in HI rats than in the sham rats and significantly higher in HI+EPO rats than in the HI rats (P<0.05). CONCLUSION: EPO may regulate VEGFR2 expression by affecting the intracranial ERK signaling pathways. PMID- 27181902 TI - [Molecular Biological Roles of Oxidative Stress in Acute Brain Ischemia]. AB - The pathogenesis of acute brain ischemia is very complex, involving multiple mechanisms including excessive free radical generation. Oxidative stress means the imbalance between the generation and removal of free radicals. Once acute brain ischemia occurs, the reactive oxygen species interact with large numbers of biomacromolecules, irreversibly change or destroy the functions of cellular lipids, proteins, and nucleic acids, and thus initiate cell signaling pathways. However, the molecular biological characteristics of oxidative stress and the way to prevent and treat acute brain ischemia still need further investigations. PMID- 27181903 TI - [Microglial Phagocytosis in the Neurodegenerative Diseases]. AB - Microglia are the resident innate immune cells in the brain. Under endogenous or exogenous stimulates, they become activated and play an important role in the neurodegenerative diseases. Microglial phagocytosis is a process of receptor mediated engulfment and degradation of apoptotic cells. In addition, microglia can phagocyte brain-specific cargo, such as myelin debris and abnormal protein aggregation. However, recent studies have shown that microglia can also phagocyte stressed-but-viable neurons, causing loss of neurons in the brain. Thus, whether microglial phagocytosis is beneficial or not in neurodegenerative disease remains controversial. This article reviews microglial phagocytosis related mechanisms and its potential roles in neurodegenerative diseases, with an attempt to provide new insights in the treatment of neurodegenerative diseases. PMID- 27181904 TI - [Autologous Fat Grafting in Scar Revision]. AB - Regenerative medicine is an emerging discipline. Adipose tissue is a rich source of fat cells and mesenchymal stem cells, and autologous fat grafting has increasingly been applied in plastic surgeries and dermatological treatments. This paper reviews the latest advances in autologous fat grafting in scar revision. PMID- 27181906 TI - Expression of macrophage migration inhibitory factor and CD74 in the inner ear and middle ear in lipopolysaccharide-induced otitis media. AB - CONCLUSION: Significant expression of macrophage migration inhibitory factor and its receptor (CD74) was observed in both the middle ear and inner ear in experimental otitis media in mice. Modulation of macrophage migration inhibitory factor and its signaling pathway might be useful in the management of inner ear inflammation due to otitis media. OBJECTIVES: Inner ear dysfunction secondary to otitis media has been reported. However, the specific mechanisms involved are not clearly understood. The aim of this study is to investigate the expression of macrophage migration inhibitory factor and CD74 in the middle ear and inner ear in lipopolysaccharide-induced otitis media. METHOD: BALB/c mice received a transtympanic injection of either lipopolysaccharide or phosphate-buffered saline (PBS). The mice were sacrificed 24 h after injection, and temporal bones were processed for polymerase chain reaction (PCR) analysis, histologic examination, and immunohistochemistry. RESULTS: PCR examination revealed that the lipopolysaccharide-injected mice showed a significant up-regulation of macrophage migration inhibitory factor in both the middle ear and inner ear as compared with the PBS-injected control mice. The immunohistochemical study showed positive reactions for macrophage migration inhibitory factor and CD74 in infiltrating inflammatory cells, middle ear mucosa, and inner ear in the lipopolysaccharide injected mice. PMID- 27181905 TI - The developmental effects of pentachlorophenol on zebrafish embryos during segmentation: A systematic view. AB - Pentachlorophenol (PCP) is a typical toxicant and prevailing pollutant whose toxicity has been broadly investigated. However, previous studies did not specifically investigate the underlying mechanisms of its developmental toxicity. Here, we chose zebrafish embryos as the model, exposed them to 2 different concentrations of PCP, and sequenced their entire transcriptomes at 10 and 24 hours post-fertilization (hpf). The sequencing analysis revealed that high concentrations of PCP elicited systematic responses at both time points. By combining the enrichment terms with single genes, the results were further analyzed using three categories: metabolism, transporters, and organogenesis. Hyperactive glycolysis was the most outstanding feature of the transcriptome at 10 hpf. The entire system seemed to be hypoxic, although hypoxia-inducible factor 1alpha (HIF1alpha) may have been suppressed by the upregulation of prolyl hydroxylase domain enzymes (PHDs). At 24 hpf, PCP primarily affected somitogenesis and lens formation probably resulting from the disruption of embryonic body plan at earlier stages. The proposed underlying toxicological mechanism of PCP was based on the crosstalk between each clue. Our study attempted to describe the developmental toxicity of environmental pollutants from a systematic view. Meanwhile, some features of gene expression profiling could serve as markers of human health or ecological risk. PMID- 27181908 TI - A non-reward attractor theory of depression. AB - A non-reward attractor theory of depression is proposed based on the operation of the lateral orbitofrontal cortex and supracallosal cingulate cortex. The orbitofrontal cortex contains error neurons that respond to non-reward for many seconds in an attractor state that maintains a memory of the non-reward. The human lateral orbitofrontal cortex is activated by non-reward during reward reversal, and by a signal to stop a response that is now incorrect. Damage to the human orbitofrontal cortex impairs reward reversal learning. Not receiving reward can produce depression. The theory proposed is that in depression, this lateral orbitofrontal cortex non-reward system is more easily triggered, and maintains its attractor-related firing for longer. This triggers negative cognitive states, which in turn have positive feedback top-down effects on the orbitofrontal cortex non-reward system. Treatments for depression, including ketamine, may act in part by quashing this attractor. The mania of bipolar disorder is hypothesized to be associated with oversensitivity and overactivity in the reciprocally related reward system in the medial orbitofrontal cortex and pregenual cingulate cortex. PMID- 27181907 TI - A Targeted Metabolomics MRM-MS Study on Identifying Potential Hypertension Biomarkers in Human Plasma and Evaluating Acupuncture Effects. AB - The critical role of metabolic abnormality in hypertension is increasingly recognized, but its biomarkers are not clearly identified. In this study, 47 chemical compounds recorded by literature were employed as target metabolites of essential hypertension (EH). We detected their content in the plasma of EH patients and healthy subjects by using the Multiple Reaction Monitoring-Mass Spectrometry (MRM-MS). After screening the most altered compounds, acupuncture was used to treat patients for 3 months and these plasma metabolites were tested again. The results showed that oleic acid (OA) and myoinositol (MI) were the most important differential metabolites between the hypertensive plasma and the healthy plasma. They were also closely correlated with 24-hour blood pressure and nocturnal dipping. Moreover, plasma OA and MI could be restored to normal levels by acupuncture, accompanying with reduction of 24-hour systolic and diastolic blood pressure [from 145.10 +/- 9.28 mm Hg to 140.70 +/- 9.59 mm Hg (P < 0.0001), and 88.35 +/- 7.92 mm Hg to 85.86 +/- 7.95 mm Hg (P = 0.0024), respectively] and improvement of circadian blood pressure rhythm. This study demonstrated that plasma OA and MI were potential hypertension biomarkers and they could be used to preliminarily assess the treating effects such as acupuncture. PMID- 27181910 TI - The efficacy and safety of teneligliptin added to ongoing metformin monotherapy in patients with type 2 diabetes: a randomized study with open label extension. AB - OBJECTIVE: The study investigated the efficacy and tolerability of teneligliptin co-administered to patients with type 2 diabetes mellitus (T2DM) who were inadequately controlled by stable metformin monotherapy >= 1000 mg/day. METHODS: A total of 447 patients from 55 European centers who completed a 14-day screening and 14-day run-in phase, received randomized double-blind treatment with 5, 10, 20 or 40 mg teneligliptin or placebo once daily, for 24 weeks. 364 patients continued treatment in a 28-week open label extension during which they received teneligliptin 20 mg once daily. RESULTS: Co-administration of teneligliptin (5 to 40 mg) with metformin demonstrated dose-related and statistically significant reductions in HbA1c after 24 weeks (-0.30 to -0.63% placebo adjusted) of double blind treatment. The greatest reduction in HbA1c was seen with teneligliptin at 40 mg (-0.63%) at Week 24. There was also a dose-dependent increase in proportion of responders achieving HbA1c < 7.0% at this endpoint. Responses were maintained throughout 28 weeks open label treatment with 20 mg teneligliptin. Treatment was well tolerated to Week 52 and the overall incidence of hypoglycemia during 52 weeks was 2.3%. CONCLUSIONS: Teneligliptin co-administered with metformin produced significant reductions in HbA1c in patients with T2DM without increasing the risk of hypoglycemia. PMID- 27181911 TI - The analytical change in plasma creatinine that constitutes a biologic/physiologic change. AB - PURPOSE: Accurate and precise measurements of creatinine are necessary to evaluate changes in kidney function related to a decreased glomerular filtration rate (GFR). When serial measurements of creatinine are monitored in an individual, it is useful to know what magnitude of an analytical change in creatinine indicates a true physiologic/biologic change in plasma creatinine that might warrant clinical intervention. METHODS: We compared results between three different methods for creatinine using large chemistry analyzers, two based on alkaline picrate (AP1 and AP2), and one based on dry-slide enzymatic conversion (ENZ). On each of three different segments or days of the study spaced 1-2months apart, we selected 10 different plasma samples having creatinine concentrations ranging from about 0.5mg/dL to 4.5mg/dL (44 to 400MUmol/L). Each sample was analyzed in triplicate on each of two same-model analyzers at each institution, then from this data we determined the precision of each model of analyzer. The within-instrument precision of each analyzer was evaluated from the differences between the triplicate results on each sample by each analyzer (mean and SD of the differences). The between-instrument precision was evaluated as the differences between results on the same sample (1, 2, 3, etc.) analyzed on different analyzers of the same model (A and B). This between-analyzer precision data was used to determine both the range and mean+/-2SD of the differences that could be used to indicate that greater changes in creatinine concentrations would represent a biologic change. RESULTS: The within-instrument precision was best for the ENZ method in comparison to the two alkaline picrate rate methods. The between-instrument precision of the 90 consecutive measurements (30 samples*triplicate analyses) between the same-model analyzers were (mean and SD of differences in mg/dL): -0.018 and 0.029 (ENZ); 0.016 and 0.11 (AP1), and 0.058 and 0.071 (AP2). CONCLUSIONS: While all three of the creatinine methods studied had good precision, the ENZ method had the best precision, such that a change of 0.07mg/dL (6MUmol/L) in serial creatinine concentrations up to 1.5mg/dL on a patient could indicate a biologic change had occurred. For the alkaline picrate methods, a measured change of creatinine of 0.23mg/dL for AP1 or 0.11mg/dL for AP2 would indicate that a physiologic change in serum/plasma creatinine has occurred. While a definite biologic change may simply represent daily variations, detecting a biologic change in creatinine more rapidly could impact the ability of creatinine to detect early and clinically significant changes in renal function. PMID- 27181912 TI - Screening for circulating RAS/RAF mutations by multiplex digital PCR. AB - Recent years have shown a large interest in the application of liquid biopsies in cancer management. Circulating tumor DNA (ctDNA) has been investigated for potential use in treatment selection, monitoring of treatment response, and early detection of recurrence. Advances have been hampered by technical challenges primarily due to the low levels of ctDNA in patients with localized disease and in patients responding to therapy. The approach presented here is a multiplex digital PCR method of screening for 31 mutations in the KRAS, NRAS, BRAF, and PIK3CA genes in the plasma. The upper level of the limit of blank, which defines the specificity of the multiplexes, was 0.006%-0.06%. Mutations found by multiplex analyses were identified and quantified by duplex analyses. The method was tested on samples from cholangiocarcinoma patients with known tumor mutational status. Mutations found in the tumor were also found in plasma samples in all cases with analyses for all other mutations being negative. There was a perfect agreement as to wild type status in tumor and plasma. The method combines a high sensitivity with the ability to analyze for several mutations at a time and could be a step towards routine clinical application of liquid biopsies. PMID- 27181913 TI - Prevention: HOPE-3 trial - targeting BP and LDL-C in at-risk patients. PMID- 27181914 TI - Clinical trials: Heart failure treatment - clinical trials versus clinical practice. PMID- 27181915 TI - Coronary artery disease: Sex-related differences in CAD and plaque characteristics. PMID- 27181909 TI - Blood biomarkers for brain injury: What are we measuring? AB - Accurate diagnosis for mild traumatic brain injury (mTBI) remains challenging, as prognosis and return-to-play/work decisions are based largely on patient reports. Numerous investigations have identified and characterized cellular factors in the blood as potential biomarkers for TBI, in the hope that these factors may be used to gauge the severity of brain injury. None of these potential biomarkers have advanced to use in the clinical setting. Some of the most extensively studied blood biomarkers for TBI include S100beta, neuron-specific enolase, glial fibrillary acidic protein, and Tau. Understanding the biological function of each of these factors may be imperative to achieve progress in the field. We address the basic question: what are we measuring? This review will discuss blood biomarkers in terms of cellular origin, normal and pathological function, and possible reasons for increased blood levels. Considerations in the selection, evaluation, and validation of potential biomarkers will also be addressed, along with mechanisms that allow brain-derived proteins to enter the bloodstream after TBI. Lastly, we will highlight perspectives and implications for repetitive neurotrauma in the field of blood biomarkers for brain injury. PMID- 27181916 TI - A survey of support systems for return to work in Japanese companies: a cross sectional study. AB - The present study aimed to survey systems in Japanese companies for supporting workers returning to work from sickness absence due to mental illness. A questionnaire survey was mailed to 3,545 companies. Support systems for return to work, sick leave, and multiple sick-listed (MSL) workers were examined. A total of 161 companies responded to the survey (response rate: 4.5%). About 80% of the companies expressed difficulty in dealing with workers with mental health problems. About half of all companies reported having reset period and financial compensation systems, as well as gradual resumption and trial attendance systems. Most large companies tended to have reset period and trial attendance systems. No association was found between company size and MSL rates. The most frequent diagnosis among workers was depression, and the mean number of sick leave days was 275.3. Although there might have been a selection bias due to the low response rate, the results of this study are expected to be useful for companies when formulating employment systems. PMID- 27181917 TI - Psychophysically determining the maximum acceptable weight of lift for polypropylene laminated bags. AB - The objective of this study was to psychophysically determine the maximum acceptable weight of lift (MAWL) for polypropylene (PP) laminated bags. Twelve men were requested to decide their MAWLs under various task combinations involving 3 lifting ranges, 3 lifting frequencies, and 2 hand conditions. The results revealed that the MAWL was significantly affected by the frequency and range variables (all p<.001), whereas the hand condition did not influence the MAWL. The participants exhibited relatively low MAWL values compared with subjects in previous studies, especially in infrequent lifts. The results of multiple stepwise regression revealed that certain anthropometric data (e.g., chest circumference, wrist circumference, and acromial height) accounted for the percentage of variance for the determined MAWLs, ranging from 56.2% to 83.4%. These data can be obtained simply and quickly, and are considered the superior predictors for MAWL determination when handling PP laminated bags. PMID- 27181919 TI - Different stabilities of liposomes containing saturated and unsaturated lipids toward the addition of cyclodextrins. AB - Liposomes composed of unsaturated lipids were more stable than those containing saturated lipids toward DMe-beta-CDx, DMe-alpha-CDx and DMe-beta-CDx. The Hill coefficient values (n) indicated that the saturated lipid.DMe-CDx complexes had stoichiometric ratios in the range of 1 : 3-1 : 4, while the unsaturated lipid.DMe-CDx complexes had ratios in the range of 1 : 1.5-1 : 3. That is, a cis alkene group in the unsaturated lipids prevented complexation with a second DMe CDx in the direction toward each acyl chain. Furthermore, the liposomes composed of the unsaturated lipids were much slower to form precipitates upon the addition of alpha-CDx than those of the saturated lipids. To the best of our knowledge, this is the first example showing that CDxs interact with unsaturated lipids. PMID- 27181918 TI - Self-regenerating and hybrid irreversible/reversible PDMS microfluidic devices. AB - This paper outlines a straightforward, fast, and low-cost method to fabricate polydimethylsiloxane (PDMS) chips. Termed sandwich bonding (SWB), this method requires only a laboratory oven. Initially, SWB relies on the reversible bonding of a coverslip over PDMS channels. The coverslip is smaller than the substrate, leaving a border around the substrate exposed. Subsequently, a liquid composed of PDMS monomers and a curing agent is poured onto the structure. Finally, the cover is cured. We focused on PDMS/glass chips because of their key advantages in microfluidics. Despite its simplicity, this method created high-performance microfluidic channels. Such structures featured self-regeneration after leakages and hybrid irreversible/reversible behavior. The reversible nature was achieved by removing the cover of PDMS with acetone. Thus, the PDMS substrate and glass coverslip could be detached for reuse. These abilities are essential in the stages of research and development. Additionally, SWB avoids the use of surface oxidation, half-cured PDMS as an adhesive, and surface chemical modification. As a consequence, SWB allows surface modifications before the bonding, a long time for alignment, the enclosure of sub-micron channels, and the prototyping of hybrid devices. Here, the technique was successfully applied to bond PDMS to Au and Al. PMID- 27181921 TI - Adjusting for calendar time in a TND influenza study. PMID- 27181922 TI - Local microstructure evolution at shear bands in metallic glasses with nanoscale phase separation. AB - At room temperature, plastic flow of metallic glasses (MGs) is sharply localized in shear bands, which are a key feature of the plastic deformation in MGs. Despite their clear importance and decades of study, the conditions for formation of shear bands, their structural evolution and multiplication mechanism are still under debate. In this work, we investigate the local conditions at shear bands in new phase-separated bulk MGs containing glassy nanospheres and exhibiting exceptional plasticity under compression. It is found that the glassy nanospheres within the shear band dissolve through mechanical mixing driven by the sharp strain localization there, while those nearby in the matrix coarsen by Ostwald ripening due to the increased atomic mobility. The experimental evidence demonstrates that there exists an affected zone around the shear band. This zone may arise from low-strain plastic deformation in the matrix between the bands. These results suggest that measured property changes originate not only from the shear bands themselves, but also from the affected zones in the adjacent matrix. This work sheds light on direct visualization of deformation-related effects, in particular increased atomic mobility, in the region around shear bands. PMID- 27181920 TI - Translocation of 40 nm diameter nanowires through the intestinal epithelium of Daphnia magna. AB - Nanowires (NWs) have unique electrical and optical properties of value for many applications including lighting, sensing, and energy harnessing. Consumer products containing NWs increase the risk of NWs being released in the environment, especially into aquatic ecosystems through sewage systems. Daphnia magna is a common, cosmopolitan freshwater organism sensitive to toxicity tests and represents a likely entry point for nanoparticles into food webs of aquatic ecosystems. Here we have evaluated the effect of NW diameter on the gut penetrance of NWs in Daphnia magna. The animals were exposed to NWs of two diameters (40 and 80 nm) and similar length (3.6 and 3.8 MUm, respectively) suspended in water. In order to locate the NWs in Daphnia, the NWs were designed to comprise one inherently fluorescent segment of gallium indium phosphide (GaInP) flanked by a gallium phosphide (GaP) segment. Daphnia mortality was assessed directly after 24 h of exposure and 7 days after exposure. Translocation of NWs across the intestinal epithelium was investigated using confocal fluorescence microscopy directly after 24 h of exposure and was observed in 89% of Daphnia exposed to 40 nm NWs and in 11% of Daphnia exposed to 80 nm NWs. A high degree of fragmentation was observed for NWs of both diameters after ingestion by the Daphnia, although 40 nm NWs were fragmented to a greater extent, which could possibly facilitate translocation across the intestinal epithelium. Our results show that the feeding behavior of animals may enhance the ability of NWs to penetrate biological barriers and that penetrance is governed by the NW diameter. PMID- 27181923 TI - Gonadotropin-releasing hormone agonist for luteal phase support: the origin of the concept, current experience, mechanism of action and future perspectives. PMID- 27181925 TI - Gestational surrogacy: a call for safer practice. PMID- 27181924 TI - Transplantations of frozen-thawed ovarian tissue demonstrate high reproductive performance and the need to revise restrictive criteria. AB - OBJECTIVE: To report the single-center results of orthotopic retransplantations of cryopreserved ovarian tissue in cancer survivors and evaluate the validity of commonly accepted procedure limitations. DESIGN: Prospective cohort study. SETTING: Tertiary university-affiliated assisted reproduction technology (ART) and oncology centers. PATIENT(S): Twenty cancer survivors who underwent ovarian transplantation of frozen-thawed ovarian tissue with the aim to conceive. INTERVENTION(S): Ovarian tissue cryopreservation (OTCP) and transplantation, endocrine monitoring, in vitro fertilization (IVF). MAIN OUTCOME MEASURE(S): Endocrine profile, IVF, pregnancies, live births. RESULT(S): The patient ages at tissue harvesting ranged from 14 to 39 years. Fifteen women had hematologic malignancies, and two had leukemia (chronic myelogenous leukemia and acute myelogenous leukemia). Ten patients were exposed to nonsterilizing chemotherapy before OTCP. After transplantation, the endocrine recovery rate was 93%. Fourteen patients underwent IVF treatments with a fertilization rate of 58%. Sixteen pregnancies were achieved (10 after IVF, 6 spontaneous), resulting in 10 live births, two (twins) after harvesting from the mother at the age of 37. Two pregnancies are currently ongoing. After transplantation, 53% of patients conceived, and 32% delivered at least once. One patient conceived four times. Preharversting chemotherapy exposure was not associated with inferior outcomes. All patients, including two leukemia survivors, remained cancer free. CONCLUSION(S): Orthotopic transplantation of thawed ovarian tissue is a highly effective measure to restore fertility in sterilized cancer patients. Chemotherapy exposure before harvesting and age >35 is a realistic option in selected patients. Retransplantation in leukemic patients is possible after application of maximal safety measures. These results have led the national ethical and professional authorities to decide for the first time not to consider OTCP as an experimental modality for fertility preservation. CLINICAL TRIAL REGISTRATION NUMBER: NCT02659592. PMID- 27181926 TI - Binary System Exhibiting the Nematic to Twist-Bend Nematic Transition: Behavior of Permittivity and Elastic Constants. AB - We describe measurements of the permittivity and Frank elastic constant in the nematic phase of a binary system displaying a transition between the nematic (N) and the recently discovered twist-bend nematic (NTB) phase. Among the salient features observed are (i) the existence of the NTB phase even when the system is loaded with a high concentration (~64 mol %) of a rodlike component; (ii) a clear signature in permittivity of the N-NTB transition; and (iii) a lower value of the bend elastic constant compared to the splay over a large phase space, with the difference between the two becoming a maximum for an intermediate mixture. These studies further support the surprising idea that the elastic features associated with bent molecules can be further augmented by suitable rodlike additives. PMID- 27181927 TI - GABAB receptors in the hippocampal dentate gyrus are involved in spatial learning and memory impairment in a rat model of vascular dementia. AB - The roles of gamma-aminobutyric acid (GABA) and GABAB receptors of the hippocampal dentate gyrus (DG) in spatial learning and memory impairment were investigated in a rat model of vascular dementia (VaD) established by permanent bilateral carotid occlusion. The extracellular concentration of GABA in the DG was determined by in vivo microdialysis and HPLC, and spatial learning and memory were assessed by the Morris water maze (MWM) test. Next, the possible involvement of GABAB receptors in spatial learning and memory impairments of VaD rats was examined by microinjection of its antagonist into the DG region. In VaD group rats, the extracellular concentration of GABA in the DG was significantly increased, and during MWM test, the escape latency was increased in place navigation trial and the percentage of time spent in target quadrant and the number of platform crossings were decreased in spatial probe trial, compared with the sham group. In sham-operated rats, the extracellular concentrations of glutamate (Glu) and glycine (Gly) in the DG were significantly increased during place navigation trial of MWM test, and these responses were inhibited in VaD rats. Saclofen (an antagonist of GABAB receptor) significantly attenuated the spatial learning and memory impairment in VaD rats, and partly reversed the inhibitory effects of VaD in responses of Glu and Gly in the DG during MWM test. Our results suggest that GABA and GABAB receptors in the hippocampal DG are involved in spatial learning and memory impairment in VaD rats, in part by attenuating the responses of Glu and Gly during spatial learning. PMID- 27181928 TI - Roles of the Nfu Fe-S targeting factors in the trypanosome mitochondrion. AB - Iron-sulphur clusters (ISCs) are protein co-factors essential for a wide range of cellular functions. The core iron-sulphur cluster assembly machinery resides in the mitochondrion, yet due to export of an essential precursor from the organelle, it is also needed for cytosolic and nuclear iron-sulphur cluster assembly. In mitochondria all [4Fe-4S] iron-sulphur clusters are synthesised and transferred to specific apoproteins by so-called iron-sulphur cluster targeting factors. One of these factors is the universally present mitochondrial Nfu1, which in humans is required for the proper assembly of a subset of mitochondrial [4Fe-4S] proteins. Although most eukaryotes harbour a single Nfu1, the genomes of Trypanosoma brucei and related flagellates encode three Nfu genes. All three Nfu proteins localise to the mitochondrion in the procyclic form of T. brucei, and TbNfu2 and TbNfu3 are both individually essential for growth in bloodstream and procyclic forms, suggesting highly specific functions for each of these proteins in the trypanosome cell. Moreover, these two proteins are functional in the iron sulphur cluster assembly in a heterologous system and rescue the growth defect of a yeast deletion mutant. PMID- 27181929 TI - A novel zoonotic genotype related to Echinococcus granulosus sensu stricto from southern Ethiopia. AB - Complete mitochondrial and two nuclear gene sequences of a novel genotype (GOmo) related to Echinococcus granulosus sensu stricto are described from a metacestode isolate retrieved from a human patient in southwestern Ethiopia. Phylogenetically, the genotype is positioned within the E. granulosus sensu stricto/Echinococcus felidis cluster, but cannot easily be allocated to either species. Based on different mitochondrial DNA markers, it is closest to the haplotype cluster that currently defines the species E. granulosus sensu stricto (which includes variants showing the widely cited G1, G2 and G3 sequences), but is clearly not part of this cluster. Pairwise distances between GOmo and E. granulosus sensu stricto are in the range of those between the most distant members of the Echinococcus canadensis complex (G6-10) that were recently proposed as separate species. At this stage, we prefer to list GOmo informally as a genotype rather than giving it any taxonomic rank because our knowledge rests on a single isolate from a dead-end host (human), and its lifecycle is unknown. According to data on molecularly characterised Echinococcus isolates from this region, GOmo has never been found in the usual livestock species that carry cystic echinococcosis and the possibility of a wildlife source of this newly recognised zoonotic agent cannot be excluded. The discovery of GOmo adds complexity to the already diverse array of cystic echinococcosis agents in sub Saharan Africa and challenges hypotheses on the biogeographical origin of the E. granulosus sensu stricto clade. PMID- 27181930 TI - Self-assembly of high-nuclearity lanthanide-based nanoclusters for potential bioimaging applications. AB - Two series of Cd-Ln and Ni-Ln clusters [Ln8Cd24L12(OAc)44(48)Cl4(0)] and [Ln8Ni6L6(OAc)24(EtOH)6(H2O)2] were constructed using a flexible ligand. The Cd Ln clusters exhibit interesting nano-drum-like structures which allows direct visualization by TEM. Luminex MicroPlex Microspheres loaded with the Cd-Sm cluster were visualized using epifluorescence microscopy. Cytotoxicity studies on A549 and AGS cancer cell lines showed that the materials have mild to moderate cytotoxicity. PMID- 27181931 TI - Case of disseminated pyomyositis in poorly controlled type 2 diabetes mellitus with diabetic ketoacidosis. AB - Primary pyomyositis is a pyogenic and uncommon infection of skeletal muscle, which is mainly observed in tropical areas and/or human immunodeficiency virus patients. In non-human immunodeficiency virus infected patients, the most common cause is diabetes mellitus. Because of its rarity, the accurate diagnosis is often challenging. Staphylococcus aureus is the most common causative bacteria. According to the severity, pyomyositis is divided into three stages, and the late stage is occasionally lethal. The present case was compatible with the most advanced stage. Therefore, it was very difficult to save her life without precise and timely diagnosis. Furthermore, in the invasive stage, surgical drainage and broad-spectrum antibiotics should be given for a long enough period. Here, we report a case of a Japanese woman who developed disseminated abscesses under poorly controlled diabetic conditions accompanied by ketoacidosis, but was successfully treated without any sequelae. PMID- 27181932 TI - Interactions between cadmium and decabrominated diphenyl ether on blood cells count in rats-Multiple factorial regression analysis. AB - The objective of this study was to assess toxicity of Cd and BDE-209 mixture on haematological parameters in subacutely exposed rats and to determine the presence and type of interactions between these two chemicals using multiple factorial regression analysis. Furthermore, for the assessment of interaction type, an isobologram based methodology was applied and compared with multiple factorial regression analysis. Chemicals were given by oral gavage to the male Wistar rats weighing 200-240g for 28days. Animals were divided in 16 groups (8/group): control vehiculum group, three groups of rats were treated with 2.5, 7.5 or 15mg Cd/kg/day. These doses were chosen on the bases of literature data and reflect relatively high Cd environmental exposure, three groups of rats were treated with 1000, 2000 or 4000mg BDE-209/kg/bw/day, doses proved to induce toxic effects in rats. Furthermore, nine groups of animals were treated with different mixtures of Cd and BDE-209 containing doses of Cd and BDE-209 stated above. Blood samples were taken at the end of experiment and red blood cells, white blood cells and platelets counts were determined. For interaction assessment multiple factorial regression analysis and fitted isobologram approach were used. In this study, we focused on multiple factorial regression analysis as a method for interaction assessment. We also investigated the interactions between Cd and BDE 209 by the derived model for the description of the obtained fitted isobologram curves. Current study indicated that co-exposure to Cd and BDE-209 can result in significant decrease in RBC count, increase in WBC count and decrease in PLT count, when compared with controls. Multiple factorial regression analysis used for the assessment of interactions type between Cd and BDE-209 indicated synergism for the effect on RBC count and no interactions i.e. additivity for the effects on WBC and PLT counts. On the other hand, isobologram based approach showed slight antagonism for the effects on RBC and WBC while no interactions were proved for the joint effect on PLT count. These results confirm that the assessment of interactions between chemicals in the mixture greatly depends on the concept or method used for this evaluation. PMID- 27181933 TI - Gender influence on manganese induced depression-like behavior and Mn and Fe deposition in different regions of CNS and excretory organs in intraperitoneally exposed rats. AB - Manganese (Mn) is an essential metal for mammals. It can modulate the action of endogenous substances, as neurotransmitters, but in excess also can trigger known neurotoxic effects. Many studies have been conducted assessing Mn neurotoxicity. However, Mn bioaccumulation in different brain tissues and behavior effects involving gender-specific studies are conflicted in the literature. Therefore, the aim of this work was to compare Mn effects, after 30days of intraperitoneal treatment, in male and female rats, submitted to forced swim and open field tests. After that, were evaluated Mn and Fe tissue levels in CNS, liver, and kidneys. Wistar rats were divided into saline, Mn 1mg/kg, Mn 5mg/kg, and imipramine (as forced swim control). Then, animals were euthanized by anesthesia overdose followed by decapitation and the collected tissue were striatum, hippocampus, brainstem, cortex, cerebellum, hepatic tissue, and renal tissue. Mn and Fe were determined by ICP-MS. There was a dose-dependent effect on accumulation of Mn in the cerebellum and brainstem to the dosage of 5mg/kg. In hippocampus there were bioaccumulation differences between gender and dose, and an increase of Fe in the groups exposed to Mn. Excess metals in the brain dissected has a strong influence on memory and learning processes and suggests pro-depressive effects, possibly triggered by the reduction of monoamines due to excessive metal bioaccumulation. It was concluded that, under this experimental design, Mn exposure cause metal deposition on dissected CNS, liver and kidney. There an effect at lower doses that was gender-dependent and males had more pronounced behavioral damage compared to females, although with increasing dose, females had an indication of motor damage. PMID- 27181934 TI - Stimulatory effects of combined endocrine disruptors on MA-10 Leydig cell steroid production and lipid homeostasis. AB - Previous work in our laboratory demonstrated that in-utero exposure to a mixture of the phytoestrogen Genistein (GEN), and plasticizer DEHP, induces short- and long-term alterations in testicular gene and protein expression different from individual exposures. These studies identified fetal and adult Leydig cells as sensitive targets for low dose endocrine disruptor (ED) mixtures. To further investigate the direct effects and mechanisms of toxicity of GEN and DEHP, MA-10 mouse tumor Leydig cells were exposed in-vitro to varying concentrations of GEN and MEHP, the principal bioactive metabolite of DEHP. Combined 10MUM GEN+10MUM MEHP had a stimulatory effect on basal progesterone production. Consistent with increased androgenicity, the mRNA of steroidogenic and cholesterol mediators Star, Cyp11a, Srb1 and Hsl, as well as upstream orphan nuclear receptors Nr2f2 and Sf1 were all significantly increased uniquely in the mixture treatment group. Insl3, a sensitive marker of Leydig endocrine disruption and cell function, was significantly decreased by combined GEN+MEHP. Lipid analysis by high-performance thin layer chromatography demonstrated the ability of combined 10MUM combined GEN+MEHP, but not individual exposures, to increase levels of several neutral lipids and phospholipid classes, indicating a generalized deregulation of lipid homeostasis. Further investigation by qPCR analysis revealed a concomitant increase in cholesterol (Hmgcoa) and phospholipid (Srebp1c, Fasn) mediator mRNAs, suggesting the possible involvement of upstream LXRalpha agonism. These results suggest a deregulation of MA-10 Leydig function in response to a combination of GEN+MEHP. We propose a working model for GEN+MEHP doses relevant to human exposure involving LXR agonism and activation of other transcription factors. Taken more broadly, this research highlights the importance of assessing the impact of ED mixtures in multiple toxicological models across a range of environmentally relevant doses. PMID- 27181935 TI - Protective effects of the exopolysaccharide Lasiodiplodan against DNA damage and inflammation induced by doxorubicin in rats: Cytogenetic and gene expression assays. AB - The lasiodiplodan (LS) is a beta-(1->6)-d-glucan produced by the fungus Lasiodiplodia theobromae and some of the biological activities of LS were reported as hypoglycemic, anticoagulant, anti-proliferative and anticancer action; however, its effects on DNA instability and modulation of gene expression are still unclear. Aims of study were investigate the genotoxic effects of lasiodiplodan, and its protective activity against DNA damage induced by doxorubicin (DXR) and its impact on the expression of genes associated with DNA damage and inflammatory response pathways. Therefore, Wistar rats were treated (15 days) orally with LS (5.0; 10 and 20mg/kg bw) alone and in combination with DXR (15mg/kg bw; administrated intraperitoneally on 14th day) as well as their respective controls: distilled water and DXR. Monitoring of DNA damage was assessed by comet and micronucleus (MN) assays and gene expression was evaluated by PCR-Arrays. Treatments with LS alone did not induce disturbances on DNA; when LS was given in combination with DXR, comet and MN formations were reduced to those found in the respective controls. Moreover, LS was able to reduce the disturbances on gene expressions induced by DXR treatment, since the animals that receive LS associated with DXR showed no alteration in the expression of genes related to DNA damage response. Also, DXR induced several up- and down-regulation of several genes associated to inflammatory process, while the animals that received LS+DXR had their gene expression patterns similar to those found in the control group. In conclusion, our results showed that LS did not induce disturbances on DNA stability and significantly reduce the DNA damage and inflammation caused by DXR exposure. In addition, we give further information concerning the molecular mechanisms associated to LS protective effects which seems to be a promising nutraceutical with chemopreventive potential. PMID- 27181938 TI - Expanding Diversity without Protecting Groups: (+)-Sclareolide to Indolosesquiterpene Alkaloid Mycoleptodiscin A and Analogues. AB - Short and scalable synthesis of the complex pentacyclic indolosesquiterpene natural product mycoleptodiscin A has been achieved from commercially available diterpenoid (+)-sclareolide in 19% overall yield. This approach allows one to prepare various analogues of mycoleptodiscin using McMurry cyclization as a key reaction with just three chromatographic purifications. PMID- 27181936 TI - Renal threshold for glucose reabsorption predicts diabetes improvement by sodium glucose cotransporter 2 inhibitor therapy. AB - In the present study we examined the efficacy of sodium-glucose cotransporter 2 inhibitors on improvement of glycated hemoglobin (HbA1c) in comparison with the renal threshold for glucose reabsorption in patients with type 2 diabetes mellitus. Patients visited the hospital once a month for a regular follow-up examination with the determination of blood glucose and HbA1c levels, and urinary glucose concentration from spot urine samples. Patient samples were compared before and after ipragliflozin administration. We defined the renal threshold for glucose reabsorption as the lowest blood glucose level that correlated with the first detectable appearance of urine glucose. These data showed a significant negative correlation between improvement of HbA1c level and renal threshold for glucose reabsorption in patients treated with the sodium-glucose cotransporter 2 inhibitor. These findings show that patients who have a higher renal threshold for glucose reabsorption can be expected to more effectively respond to sodium glucose cotransporter 2 inhibitor therapy in terms of lowering HbA1c levels. PMID- 27181937 TI - Associations between metabolic risk factors and body mass index, waist circumference, waist-to-height ratio and waist-to-hip ratio in a Chinese rural population. AB - AIMS/INTRODUCTION: Obesity plays a central role in metabolic syndrome. Obesity indexes are important in clinical work. In the present study, we sought to determine the relationships between obesity indexes and metabolic risk factors. MATERIALS AND METHODS: We studied 11,568 participants over 35 years. Body mass index, waist circumference (WC), waist-to-height ratio (WHtR) and waist-to-hip ratio were measured and calculated. To compare the predictive ability of the obesity indexes in diagnosing multiple metabolic risk factors, the areas under receiver operating characteristic curves were calculated, and cut-off values were determined. A partial correlation coefficient was used to assess the intercorrelations between the obesity indexes, and to evaluate the correlations between each index and each metabolic risk factor. RESULTS: The partial correlation coefficient for WHtR and WC was 0.947. In diagnosing multiple metabolic risk factors, the WHtR areas under receiver operating characteristic curves was greater than that for the other obesity indexes in both sexes. The cut off point for the WHtR was 0.50 in men and 0.52 in women. The cut-off point for WC was 85 cm in men and 80 cm in women. CONCLUSIONS: WHtR strongly correlates with WC. The WHtR might show the same predictive ability as the WC in diagnosing multiple metabolic risk factors. PMID- 27181940 TI - Real world vaccine ethics. PMID- 27181939 TI - Myocardial Response to Milrinone in Single Right Ventricle Heart Disease. AB - OBJECTIVES: Empiric treatment with milrinone, a phosphodiesterase (PDE) 3 inhibitor, has become increasingly common in patients with single ventricle heart disease of right ventricular (RV) morphology (SRV); our objective was to characterize the myocardial response to PDE3 inhibition (PDE3i) in the pediatric population with SRV. STUDY DESIGN: Cyclic adenosine monophosphate levels, PDE activity, and phosphorylated phospholamban (PLN) were determined in explanted human ventricular myocardium from nonfailing pediatric donors (n = 10) and pediatric patients transplanted secondary to SRV. Subjects with SRV were further classified by PDE3i treatment (n = 13 with PDE3i and n = 12 without PDE3i). RESULTS: In comparison with nonfailing RV myocardium (n = 8), cyclic adenosine monophosphate levels are lower in patients with SRV treated with PDE3i (n = 12, P = .021). Chronic PDE3i does not alter total PDE or PDE3 activity in SRV myocardium. Compared with nonfailing RV myocardium, SRV myocardium (both with and without PDE3i) demonstrates equivalent phosphorylated PLN at the protein kinase A phosphorylation site. CONCLUSIONS: As evidenced by preserved phosphorylated PLN, the molecular adaptation associated with SRV differs significantly from that demonstrated in pediatric heart failure because of dilated cardiomyopathy. These alterations support a pathophysiologically distinct mechanism of heart failure in pediatric patients with SRV, which has direct implications regarding the presumed response to PDE3i treatment in this population. PMID- 27181941 TI - Identification and functional analysis of SVP ortholog in herbaceous perennial plant Gentiana triflora: Implication for its multifunctional roles. AB - Information concerning to regulation of vegetative phase and floral initiation in herbaceous perennial plants has been limited to a few plant species. To know and compare flowering regulation in a wider range of plant species, we identified and characterized SHORT VEGETATIVE PHASE (SVP)-like genes (GtSVP-L1 and GtSVP-L2) from herbaceous perennial gentian (Gentiana triflora). Apple latent spherical virus (ALSV)-mediated silencing of the GtSVP-L1 in G. triflora seedlings resulted in early flowering and shortened vegetative phase by about one-third period of time, without vernalization. This indicated that GtSVP-L1 acts as a negative regulator of flowering and vegetative phase. Seasonal change in the expression of GtSVP was monitored in the overwinter buds (OWBs) of G. triflora. It was found that the levels of GtSVP-L1 mRNA in OWBs increased concomitantly with induction and/or maintenance of dormancy, then decreased toward release from dormancy, while that of GtSVP-L2 mRNA remained low and unchanged. These results implied that, in herbaceous perennial plants, SVP ortholog might concern to activity dormancy control, as well as negative regulation in flowering. Practically, these results can be applicable to non-time-consuming technologies for breeding. PMID- 27181942 TI - Comparative study of Zn deficiency in L. sativa and B. oleracea plants: NH4(+) assimilation and nitrogen derived protective compounds. AB - Zinc (Zn) deficiency is a major problem in agricultural crops of many world regions. N metabolism plays an essential role in plants and changes in their availability and their metabolism could seriously affect crop productivity. The main objective of the present work was to perform a comparative analysis of different strategies against Zn deficiency between two plant species of great agronomic interest such as Lactuca sativa cv. Phillipus and Brassica oleracea cv. Bronco. For this, both species were grown in hydroponic culture with different Zn doses: 10MUM Zn as control and 0.01MUM Zn as deficiency treatment. Zn deficiency treatment decreased foliar Zn concentration, although in greater extent in B. oleracea plants, and caused similar biomass reduction in both species. Zn deficiency negatively affected NO3(-) reduction and NH4(+) assimilation and enhanced photorespiration in both species. Pro and GB concentrations were reduced in L. sativa but they were increased in B. oleracea. Finally, the AAs profile changed in both species, highlighting a great increase in glycine (Gly) concentration in L. sativa plants. We conclude that L. sativa would be more suitable than B. oleracea for growing in soils with low availability of Zn since it is able to accumulate a higher Zn concentration in leaves with similar biomass reduction. However, B. oleracea is able to accumulate N derived protective compounds to cope with Zn deficiency stress. PMID- 27181943 TI - Ectopic expression of a grape aspartic protease gene, AP13, in Arabidopsis thaliana improves resistance to powdery mildew but increases susceptibility to Botrytis cinerea. AB - The grape aspartic protease gene, AP13 was previously reported to be responsive, in Chinese wild Vitis quinquangularis cv. 'Shang-24', to infection by Erysiphe necator, the causal agent of powdery mildew disease, as well as to treatment with salicylic acid in V. labrusca*V. vinifera cv. 'Kyoho'. In the current study, we evaluated the expression levels of AP13 in 'Shang-24' in response to salicylic acid (SA), methyl jasmonate (MeJA) and ethylene (ET) treatments, as well as to infection by the necrotrophic fungus, Botrytis cinerea, and the transcript levels of VqAP13 decreased after B. cinerea infection and MeJA treatment, but increased following ET and SA treatments. Transgenic Arabidopsis thaliana lines over expressing VqAP13 under the control of a constitutive promoter showed enhanced resistance to powdery mildew and to the bacterium Pseudomonas syringae pv. tomato DC3000, and accumulated more callose than wild type plants, while the resistance of transgenic A. thaliana lines to B. cinerea inoculation was reduced. In addition, the expression profiles of various disease resistance- related genes in the transgenic A. thaliana lines following infection by different pathogens were compared to the equivalent profiles in the wild type plants. The results suggest that VqAP13 action promotes the SA dependent signal transduction pathway, but suppresses the JA signal transduction pathway. PMID- 27181944 TI - OsSRT1 is involved in rice seed development through regulation of starch metabolism gene expression. AB - OsSRT1 is a NAD(+)-dependent histone deacetylase, closely related to the human SIRT6 that plays key roles in genome stability and metabolic homeostasis. In this work, we investigated the role of OsSRT1 in rice seed development. Down regulation of OsSRT1 induced higher expression of Rice Starch Regulator1 (RSR1) and amylases genes in developing seeds, which resulted in a decrease of starch synthesis and an increase of starch degradation, leading to abnormal seed development. ChIP assay showed that OsSRT1 was required to reduce histone H3K9 acetylation on starch metabolism genes and transposons in developing seeds. In addition, OsSRT1 was detected to directly bind to starch metabolism genes such as OsAmy3B, OsAmy3E, OsBmy4, and OsBmy9. Our results suggested that OsSRT1-mediated histone deacetylation is involved in starch accumulation and transposon repression to regulate normal seed development. PMID- 27181945 TI - Glyoxylate cycle and metabolism of organic acids in the scutellum of barley seeds during germination. AB - During the developmental processes from dry seeds to seedling establishment, the glyoxylate cycle becomes active in the mobilization of stored oils in the scutellum of barley (Hordeum vulgare L.) seeds, as indicated by the activities of isocitrate lyase and malate synthase. The succinate produced is converted to carbohydrates via phosphoenolpyruvate carboxykinase and to amino acids via aminotransferases, while free organic acids may participate in acidifying the endosperm tissue, releasing stored starch into metabolism. The abundant organic acid in the scutellum was citrate, while malate concentration declined during the first three days of germination, and succinate concentration was low both in scutellum and endosperm. Malate was more abundant in endosperm tissue during the first three days of germination; before citrate became predominant, indicating that malate may be the main acid acidifying the endosperm. The operation of the glyoxylate cycle coincided with an increase in the ATP/ADP ratio, a buildup of H2O2 and changes in the redox state of ascorbate and glutathione. It is concluded that operation of the glyoxylate cycle in the scutellum of cereals may be important not only for conversion of fatty acids to carbohydrates, but also for the acidification of endosperm and amino acid synthesis. PMID- 27181946 TI - Transcriptome and selected metabolite analyses reveal points of sugar metabolism in jackfruit (Artocarpus heterophyllus Lam.). AB - Artocarpus heterophyllus Lam., commonly known as jackfruit, produces the largest tree-borne fruit known thus far. The edible part of the fruit develops from the perianths, and contains many sugar-derived compounds. However, its sugar metabolism is poorly understood. A fruit perianth transcriptome was sequenced on an Illumina HiSeq 2500 platform, producing 32,459 unigenes with an average length of 1345nt. Sugar metabolism was characterized by comparing expression patterns of genes related to sugar metabolism and evaluating correlations with enzyme activity and sugar accumulation during fruit perianth development. During early development, high expression levels of acid invertases and corresponding enzyme activities were responsible for the rapid utilization of imported sucrose for fruit growth. The differential expression of starch metabolism-related genes and corresponding enzyme activities were responsible for starch accumulated before fruit ripening but decreased during ripening. Sucrose accumulated during ripening, when the expression levels of genes for sucrose synthesis were elevated and high enzyme activity was observed. The comprehensive transcriptome analysis presents fundamental information on sugar metabolism and will be a useful reference for further research on fruit perianth development in jackfruit. PMID- 27181947 TI - UV-B effects on leaves-Oxidative stress and acclimation in controlled environments. AB - As the steady decline in the Earth's stratospheric ozone layer and parallel increase in solar ultraviolet-B (UV-B: 280-315nm) has come to an end, the focus of plant UV research has been shifted from regarding UV-B as threatening plant life to recognizing it as a regulatory factor. While UV-B photoreceptor mediated signaling is increasingly understood, the role of UV-B inducible reactive oxygen species is still to be explored. Earlier experiments with high UV-B irradiation doses and isolated thylakoid membranes demonstrated the potential of UV-B to trigger oxidative stress. However, under realistic UV conditions pro-oxidants cannot be reliably traced in more complex biological samples possessing an array of antioxidant defenses. In the absence of direct experimental evidence we must rely on indications and propose hypotheses on how and whether pro-oxidants, such as reactive oxygen species contribute to acclimative responses. Here we briefly review how a balance between pro-oxidants and antioxidants is affected by UV-B in whole plant experiments performed in controlled environments. A working hypothesis is proposed in which the extents of UV-induced peroxidase and superoxide dismutase activations affect the success of acclimation to UV-B. PMID- 27181948 TI - AcEBP1, an ErbB3-Binding Protein (EBP1) from halophyte Atriplex canescens, negatively regulates cell growth and stress responses in Arabidopsis. AB - An ErbB-3-binding protein gene AcEBP1, also known as proliferation-associated 2G4 gene (PA2G4s) belonging to the M24 superfamily, was obtained from the saltbush Atriplex canescens. Subcellular localization imaging showed the fusion protein AcEBP1-eGFP was located in the nucleus of epidermal cells in Nicotiana benthamiana. The AcEBP1 gene expression levels were up-regulated under salt, osmotic stress, and hormones treatment as revealed by qRT-PCR. Overexpression of AcEBP1 in Arabidopsis demonstrated that AcEBP1 was involved in root cell growth and stress responses (NaCl, osmotic stress, ABA, low temperature, and drought). These phenotypic data were correlated with the expression patterns of stress responsive genes and PR genes. The AcEBP1 transgenic Arabidopsis plants also displayed increased sensitivity under low temperature and evaluated resistance to drought stress. Together, these results demonstrate that AcEBP1 negatively affects cell growth and is a regulator under stress conditions. PMID- 27181949 TI - Review: Post-translational cross-talk between brassinosteroid and sucrose signaling. AB - A direct link has been elucidated between brassinosteroid function and perception, and sucrose partitioning and transport. Sucrose regulation and brassinosteroid signaling cross-talk at various levels, including the well described regulation of transcriptional gene expression: BZR-like transcription factors link the signaling pathways. Since brassinosteroid responses depend on light quality and quantity, a light-dependent alternative pathway was postulated. Here, the focus is on post-translational events. Recent identification of sucrose transporter-interacting partners raises the question whether brassinosteroid and sugars jointly affect plant innate immunity and plant symbiotic interactions. Membrane permeability and sensitivity depends on the number of cell surface receptors and transporters. More than one endocytic route has been assigned to specific components, including brassinosteroid-receptors. The number of such proteins at the plasma membrane relies on endocytic recycling, internalization and/or degradation. Therefore, vesicular membrane trafficking is gaining considerable attention with regard to plant immunity. The organization of pattern recognition receptors (PRRs), other receptors or transporters in membrane microdomains participate in endocytosis and the formation of specific intracellular compartments, potentially impacting biotic interactions. This minireview focuses on post-translational events affecting the subcellular compartmentation of membrane proteins involved in signaling, transport, and defense, and on the cross-talk between brassinosteroid signals and sugar availability. PMID- 27181950 TI - Soybean SPX1 is an important component of the response to phosphate deficiency for phosphorus homeostasis. AB - Phosphate (Pi) homeostasis is required for plant growth and development, but the Pi-signaling pathways in plants still remain largely unknown. Proteins only containing the SPX domain are very important in phosphate (Pi) homeostasis and signaling transduction. In the T-DNA insertion Arabidopsis mutant spx3, AtPHT1-4, AtPHT1-5, AtACP5, AtRNS, and AtAT4 expression levels were increased under Pi sufficient condition and low Pi condition compared with WT. Meanwhile, the expression levels of these phosphate starvation genes was inhibited in OXSPX1 and spx3/OXSPX1 compared with WT, only under Pi-sufficient condition. These imply that GmSPX1 may negatively control the transcription of Pi starvation responsive genes indirectly. However, there were no differences between expression levels of these PSI genes in spx3 and those in WT under -Pi conditions. These facts imply that the negative regulation of GmSPX1 and AtSPX3 on PSI genes is depending on Pi concentration. Consistent with this, GmSPX1 overexpression in the WT and spx3 decreased the total Pi concentration in plants and changed root hair morphology, suppressing the elongation and number of root hairs compared with the WT and spx3. The yeast two-hybrid assays and BiFC assays demonstrated that GmSPX1 could interact with GmMYB48.The qRT-PCR analysis showed that GmMYB48 is a new phosphate starvation induced transcription factor in soybean. Also, GmSPX1 overexpression led to decreased transcripts of AtMYB4, an ortholog of GmMYB48, in OXSPX1. Together, these results suggest that GmSPX1 is a negative regulator in the Pi signaling network of soybean, and the interaction of GmSPX1/GmMYB48 can be considered a potential candidate suppressor. PMID- 27181951 TI - Review: Mechanisms of ammonium toxicity and the quest for tolerance. AB - Ammonium sensitivity of plants is a worldwide problem, constraining crop production. Prolonged application of ammonium as the sole nitrogen source may result in physiological and morphological disorders that lead to decreased plant growth and toxicity. The main causes of ammonium toxicity/tolerance described until now include high ammonium assimilation by plants and/or low sensitivity to external pH acidification. The various ammonium transport-related components, especially the non-electrogenic influx of NH3 (related to the depletion of (15)N) and the electrogenic influx of NH4(+), may contribute to ammonium accumulation, and therefore to NH3 toxicity. However, this accumulation may be influenced by increasing K(+) concentration in the root medium. Recently, new insights have been provided by "omics" studies, leading to a suggested involvement of GDP mannose-pyrophosphorylase in the response pathways of NH4(+) stress. In this review, we highlight the cross-talk signaling between nitrate, auxins and NO, and the importance of the connection of the plants' urea cycle to metabolism of polyamines. Overall, the tolerance and amelioration of ammonium toxicity are outlined to improve the yield of ammonium-grown plants. This review identifies future directions of research, focusing on the putative importance of aquaporins in ammonium influx, and on genes involved in ammonium sensitivity and tolerance. PMID- 27181952 TI - Overexpression of wheat ubiquitin gene, Ta-Ub2, improves abiotic stress tolerance of Brachypodium distachyon. AB - Ubiquitination plays an important role in regulating plant's development and adaptability to abiotic stress. To investigate the possible functions of a wheat monoubiquitin gene Ta-Ub2 in abiotic stress in monocot and compare it with that in dicot, we generated transgenic Brachypodium plants overexpressing Ta-Ub2 under the control of CaMV35s and stress-inducible RD29A promoters. The constitutive expression of Ta-Ub2 displayed slight growth inhibition in the growth of transgenic Brachypodium distachyon under the control conditions. However, this inhibition was minimized by expression of Ta-Ub2 under the control of stress inducible RD29A promoter. Compared with WT, the transgenic plants preserved more water and showed higher enzymatic antioxidants under drought stress, which might be related to the change in the expression of some antioxidant genes. The expression of C-repeat binding factors transcription factor genes in the transgenic B. distachyon lines were upregulated under water stress. Salt and cold tolerances of transgenic B. distachyon were also improved. Although the phenotypic changes in the transgenic plants were different, overexpression of Ta Ub2 improved the abiotic stress tolerance in both dicot and monocot plants. The improvement in Ta-Ub2 transgenic plants in abiotic stress tolerance might be, at least partly, through regulating the gene expression and increasing the enzymatic antioxidants. PMID- 27181981 TI - Investigating the Role of Thiazide-Like Diuretics in Acute Heart Failure: Potential Approach to an Unmet Need. PMID- 27181953 TI - Gene expression profiling during seed-filling process in peanut with emphasis on oil biosynthesis networks. AB - Pod-filling is an important stage of peanut (Arachis hypogaea) seed development. It is partially controlled by genetic factors, as cultivars considerably vary in pod-filling potential. Here, a study was done to detect changes in mRNA levels that accompany pod-filling processes. Four seed developmental stages were sampled from two peanut genotypes differing in their oil content and pod-filling potential. Transcriptome data were generated by RNA-Seq and explored with respect to genic and subgenomic patterns of expression. Very dynamic transcriptomic changes occurred during seed development in both genotypes. Yet, general higher expression rates of transcripts and an enrichment in processes involved "energy generation" and "primary metabolites" were observed in the genotype with the better pod-filling ("Hanoch"). A dataset of 584 oil-related genes was assembled and analyzed, resulting in several lipid metabolic processes highly expressed in Hanoch, including oil storage and FA synthesis/elongation. Homoeolog-specific gene expression analysis revealed that both subgenomes contribute to the oil genes expression. Yet, biases were observed in particular parts of the pathway with possible biological meaning, presumably explaining the genotypic variation in oil biosynthesis and pod-filling. This study provides baseline information and a resource that may be used to understand development and oil biosynthesis in the peanut seeds. PMID- 27181986 TI - Time-dependent SERS spectra monitoring the dynamic adsorption behavior of bipyridine isomerides combined with bianalyte method. AB - Based on the bianalyte method, time-dependent surface-enhanced Raman spectrosopy (SERS) spectra were applied to observe and study the competitive adsorption of bipyridine isomerides 2,2'-bpy and 4,4'-bpy. These time-dependent SERS spectra offer a significant advantage for observing the continuous SERS spectra of analyte with 2 s resolution, letting one monitor real-time competitive adsorption and corresponding SERS signal intensity for mixed or pure analyte type events under different concentrations. In this study, we report experimental evidence of competitive adsorption of two bipyridine isomerides using SERS mapping and independent spectra in chronological order. On the one hand, the time-dependent SERS spectra of 2,2'-bpy were prior dominated in the early stage either in high concentration or in low concentration. On the other hand, pure type 2,2'-bpy or 4,4'-bpy events only occurred for strong intensity, whereas weak intensity events exhibited more mixed analytes in low concentration, showing a great difference from those at the higher concentration. In addition, we believe that these results and this evidence can motivate the use of time-dependent SERS spectra for distinguishing the fingerprint information of several molecules from similar isomeride molecules in chemical and biological systems. PMID- 27181987 TI - A water-soluble colorimetric two-photon probe for discrimination of different palladium species and its application in bioimaging. AB - A novel water-soluble colorimetric and fluorescent palladium probe with excellent selectivity and sensitivity has been designed. Notably, based on a palladium triggered terminal allyl ether cleavage reaction, the probe could detect and discriminate Pd(0) and Pd(2+)/Pd(4+) in about 2.5 min at room temperature with a low detection limit (0.29 ppb) and significant colour change (from light yellow to pink). The probe could serve as an excellent "naked-eye" colorimetric probe for selective and quantitative determination of palladium in aqueous solutions. Moreover, it could be used as a two-photon palladium probe for in vitro/vivo and three-dimensional imaging with low cytotoxicity and autofluorescence. PMID- 27181988 TI - Muti-component nanocomposite of nickel and manganese oxides with enhanced stability and catalytic performance for non-enzymatic glucose sensors. AB - A muti-component nanocomposite of nickel and manganese oxides with a uniformly dispersed microspherical structure has been fabricated by a hydrothermal synthesis method. The as-prepared nanocomposite has been employed as a sensing material for non-enzymatic glucose detection and shown excellent electrocatalytic activity, such as high sensitivities of 82.44 MUA mM(-1) cm(-2) and 27.92 MUA mM( 1) cm(-2) over the linear range of 0.1-1 mM and 1-4.5 mM, respectively, a low detection limit of 0.2 MUM and a fast response time of <3 s. Moreover, satisfactory specificity and excellent stability have also been achieved. The results demonstrate that a muti-component nanocomposite of nickel and manganese oxides has great potential applications as glucose sensors. PMID- 27181989 TI - Influence of Albumin Configuration by the Chiral Polymer-Grafted Gold Nanoparticles. AB - The interaction between nanoparticles (NPs) and proteins is a topic of high relevance for the medical application of NPs. This study reveals the molecular chirality on NP surfaces as an indirect regulator of the interaction between proteins and NPs. Poly(N-acryloyl-valine) (PAV) polymers with d- and l configurations were conjugated onto gold NPs with a size of 5 nm to obtain the l PAV-AuNPs and d-PAV-AuNPs, respectively. They had same chemical composition and surface grafting density but different surface chirality. The isothermal titration calorimetry results showed that adsorption of bovine serum albumin onto the l-PAV-AuNPs and d-PAV-AuNPs was primarily driven by electrostatic interaction. Dynamic light scattering, circular dichroism spectroscopy, fluorescence quenching, and isothermal titration calorimetry characterizations revealed that bovine serum albumin molecules adopted both side-on and end-on configurations on the d-PAV-AuNPs, whereas only end-on configuration on the l-PAV AuNPs. PMID- 27181990 TI - Airborne engineered nanomaterials in the workplace-a review of release and worker exposure during nanomaterial production and handling processes. AB - For exposure and risk assessment in occupational settings involving engineered nanomaterials (ENMs), it is important to understand the mechanisms of release and how they are influenced by the ENM, the matrix material, and process characteristics. This review summarizes studies providing ENM release information in occupational settings, during different industrial activities and using various nanomaterials. It also assesses the contextual information - such as the amounts of materials handled, protective measures, and measurement strategies - to understand which release scenarios can result in exposure. High-energy processes such as synthesis, spraying, and machining were associated with the release of large numbers of predominantly small-sized particles. Low-energy processes, including laboratory handling, cleaning, and industrial bagging activities, usually resulted in slight or moderate releases of relatively large agglomerates. The present analysis suggests that process-based release potential can be ranked, thus helping to prioritize release assessments, which is useful for tiered exposure assessment approaches and for guiding the implementation of workplace safety strategies. The contextual information provided in the literature was often insufficient to directly link release to exposure. The studies that did allow an analysis suggested that significant worker exposure might mainly occur when engineering safeguards and personal protection strategies were not carried out as recommended. PMID- 27181991 TI - Genetic heterogeneity within the HLA region in three distinct clinical subgroups of myasthenia gravis. AB - This study aims to investigate genetic susceptibility to early-onset and late onset anti-acetylcholine receptor antibody positive myasthenia gravis (EOMG and LOMG) and anti-muscle specific kinase antibody positive MG (MuSK-MG) at genome wide level in a single population. Using a custom-designed array and imputing additional variants and the classical HLA alleles in 398 patients, we detected distinct associations. In EOMG, rs113519545 in the HLA class I region (OR=5.71 [3.77-8.66], P=2.24*10(-16)), HLA-B*08:01 (OR=7.04 [3.95-12.52], P=3.34*10(-11)) and HLA-C*07:01 (OR=2.74 [1.97-3.81], P=2.07(-9)), in LOMG, rs111256513 in the HLA class II region (OR=2.22 [1.59-3.09], P=2.48*10(-6)) and in MuSK-MG, an intronic variant within HLA-DQB1 (rs68081734, OR=5.86, P=2.25*10(-14)) and HLA DQB1*05:02 (OR=8.56, P=6.88*10(-13)) revealed the most significant associations for genome-wide significance. Differential genetic susceptibility within the HLA to EOMG, LOMG and MuSK-MG has been established in a population from Turkey. PMID- 27181992 TI - Maintenance of Mycobacterium tuberculosis-specific T cell responses in End Stage Renal Disease (ESRD) and implications for diagnostic efficacy. AB - End-stage renal disease (ESRD) patients exhibit elevated risk of tuberculosis (TB) reactivation, but current diagnostics, including the interferon gamma release assay (IGRA), exhibit poor sensitivity in ESRD. We tested 80 ESRD patients and found an 18.75% prevalence of IGRA positivity. A subset of patients was assessed for Mtb-specific expression of 44 cytokines/chemokines, and CD4+ T cell phenotype and function. Similar to non-ESRD IGRA+ individuals, Mtb-specific IFNgamma, IL-1RA, IP-10, MCP-3 and IL-2 responses were identified in the ESRD IGRA+ group. 27% of the ESRD IGRA- group exhibited MCP-3 or IL-2 Mtb-specific responses, which may identify cases of latent TB infection in ESRD. Stimulation of PBMC with PPD demonstrated similar CD4+ T cell production of IFNgamma, TNFalpha and GM-CSF by ESRD patients. The reported low sensitivity of the IGRA in ESRD cohorts is therefore unlikely to be due to poor T cell cytokine secretion, and may instead reflect defects in antigen presentation. PMID- 27181994 TI - Correction to "Pyridine Ligand Rotation in Self-Assembled Trigonal Prisms. Evidence for Intracage Solvent Vapor Bubbles". PMID- 27181995 TI - Electron-beam irradiation induced transformation of Cu2(OH)3NO3 nanoflakes into nanocrystalline CuO. AB - The transmission electron microscope electron-beam (TEM e-beam) as a material modification tool has been demonstrated. The material modification is realised in the high-resolution TEM mode (largest condenser aperture, 150 MUm, and 200 nm spot size) at a 200 keV beam energy. The Cu2(OH)3NO3 (CHN) nanoflakes used in this study were microwave solution processed that were layered single crystals and radiation sensitive. The single domain CHN flakes disintegrate into a large number of individual CuO crystallites within a 90 s span of time. The sequential bright-field, dark-field, and selected area electron diffraction modes were employed to record the evolved morphology, microstructural changes, and structural transformation that validate CHN modification. High-resolution transmission electron microscopy imaging of e-beam irradiated regions unambiguously supports the growth of CuO nanoparticles (11.8(3.2) nm in diameter). This study demonstrates e-beam irradiation induced CHN depletion, subsequent nucleation and growth of nanocrystalline CuO regions well embedded in the parent burnt porous matrix which can be useful for miniaturized sensing applications. NaBH4 induced room temperature reduction of CHN to elemental Cu and its printability on paper was also demonstrated. PMID- 27181993 TI - A pre-eclampsia-associated Epstein-Barr virus antibody cross-reacts with placental GPR50. AB - To characterize antibody specificities associated with pre-eclampsia (PE), bacterial displayed peptide library screening and evolution was applied to identify peptide epitopes recognized by plasma antibodies present in women with PE near the time of delivery. Pre-eclamptic women exhibited elevated IgG1 titers towards a peptide epitope KRPSCIGCK within the Epstein-Barr virus nuclear antigen 1 (EBNA-1). EBNA-1 epitope antibodies cross-reacted with a similar epitope within the extracellular N-terminus of the human G protein-coupled receptor, GPR50, expressed in human placental tissue and immortalized placental trophoblast cells. We observed increased antibody binding activity to epitopes from EBNA-1 and GPR50 among women with PE (n=42) compared to healthy-outcome pregnancies (n=43) and nulligravid samples (n=21). The EBNA-1 peptide potently blocked binding of the PE associated antibody to the GPR50 epitope (IC50=58-81pM). These results reveal the existence of molecular mimicry between EBNA-1 and placental GPR50, supporting a mechanism for IgG1 deposition in the pre-eclamptic placenta. PMID- 27181997 TI - Polymorphism in alpha-sexithiophene crystals: relative stability and transition path. AB - We present a joint theoretical and experimental study to investigate polymorphism in alpha-sexithiophene (6T) crystals. By means of density-functional theory calculations, we clarify that the low-temperature phase is favorable over the high-temperature one, with higher relative stability up to 50 meV per molecule. This result is in agreement with our thermal desorption measurements. We also propose a transition path between the high- and low-temperature 6T polymorphs, estimating an upper bound for the energy barrier of about 1 eV per molecule. The analysis of the electronic properties of the investigated 6T crystal structures complements our study. PMID- 27181996 TI - Comparative Cost-Effectiveness of Conservative or Intensive Blood Pressure Treatment Guidelines in Adults Aged 35-74 Years: The Cardiovascular Disease Policy Model. AB - The population health effect and cost-effectiveness of implementing intensive blood pressure goals in high-cardiovascular disease (CVD) risk adults have not been described. Using the CVD Policy Model, CVD events, treatment costs, quality adjusted life years, and drug and monitoring costs were simulated over 2016 to 2026 for hypertensive patients aged 35 to 74 years. We projected the effectiveness and costs of hypertension treatment according to the 2003 Joint National Committee (JNC)-7 or 2014 JNC8 guidelines, and then for adults aged >=50 years, we assessed the cost-effectiveness of adding an intensive goal of systolic blood pressure <120 mm Hg for patients with CVD, chronic kidney disease, or 10 year CVD risk >=15%. Incremental cost-effectiveness ratios <$50 000 per quality adjusted life years gained were considered cost-effective. JNC7 strategies treat more patients and are more costly to implement compared with JNC8 strategies. Adding intensive systolic blood pressure goals for high-risk patients prevents an estimated 43 000 and 35 000 annual CVD events incremental to JNC8 and JNC7, respectively. Intensive strategies save costs in men and are cost-effective in women compared with JNC8 alone. At a willingness-to-pay threshold of $50 000 per quality-adjusted life years gained, JNC8+intensive had the highest probability of cost-effectiveness in women (82%) and JNC7+intensive the highest probability of cost-effectiveness in men (100%). Assuming higher drug and monitoring costs, adding intensive goals for high-risk patients remained consistently cost effective in men, but not always in women. Among patients aged 35 to 74 years, adding intensive blood pressure goals for high-risk groups to current national hypertension treatment guidelines prevents additional CVD deaths while saving costs provided that medication costs are controlled. PMID- 27181998 TI - Randomized clinical trial of the safety and efficacy of sitagliptin and metformin co-administered to Chinese patients with type 2 diabetes mellitus. AB - INTRODUCTION: The results of a clinical trial to evaluate the efficacy and safety of initial combination therapy with sitagliptin and metformin in Chinese patients with type 2 diabetes and inadequate glycemic control are reported here. MATERIALS AND METHODS: This was a multicenter, randomized, double-blind, placebo controlled, parallel group, 24-week clinical trial carried out in China. Patients (n = 744) with type 2 diabetes and inadequate glycemic control (glycated hemoglobin >=7.5 and <=11.0%) who were either drug-naive or washed out of previous therapy were randomized in equal ratios to sitagliptin 100 mg once daily (q.d.; S100), metformin 500 mg twice daily (b.i.d.; M1000), metformin 850 mg b.i.d. (M1700), sitagliptin 50 mg b.i.d. plus metformin 500 mg b.i.d. (S100/M1000), sitagliptin 50 mg b.i.d. plus metformin 850 mg b.i.d. (S100/M1700), or placebo. RESULTS: The mean baseline glycated hemoglobin in randomized patients was 8.7%. Least squares mean changes from baseline in glycated hemoglobin were 0.59% (placebo), -0.99% (S100), -1.29% (M1000), -1.56% (M1700), -1.67% (S100/M1000) and -1.83% (S100/M1700) (P < 0.05 for each active group vs placebo, for S100/M1700 and S100/M1000 vs S100, and for S100/M1000 vs M1000). All treatments were generally well-tolerated. The overall incidence of hypoglycemia (symptomatic or asymptomatic) was higher in the two co-administration groups (S100/M1700 and S100/M1000) compared with the placebo. The incidence of symptomatic hypoglycemia was low, and similar, across all treatment groups. The incidences of gastrointestinal adverse events were generally higher in high-dose metformin groups than in the placebo group. CONCLUSIONS: In Chinese patients with type 2 diabetes, initial combination therapy with sitagliptin and metformin was generally well-tolerated, and provided improvement in glycemic control. PMID- 27182002 TI - Diabetes and shoulder disorders. PMID- 27181999 TI - Bariatric surgery is associated with improvement in kidney outcomes. AB - Severe obesity is associated with increased risk of kidney disease. Whether bariatric surgery reduces the risk of adverse kidney outcomes is uncertain. To resolve this we compared the risk of estimated glomerular filtration rate (eGFR) decline of >=30% and doubling of serum creatinine or end-stage renal disease (ESRD) in 985 patients who underwent bariatric surgery with 985 patients who did not undergo such surgery. Patients were matched on demographics, baseline body mass index, eGFR, comorbidities, and previous nutrition clinic use. Mean age was 45 years, 97% were white, 80% were female, and 33% had baseline eGFR <90 ml/min per 1.73 m(2). Mean 1-year weight loss was 40.4 kg in the surgery group compared with 1.4 kg in the matched cohort. Over a median follow-up of 4.4 years, 85 surgery patients had an eGFR decline of >=30% (22 had doubling of serum creatinine/ESRD). Over a median follow-up of 3.8 years, 177 patients in the matched cohort had an eGFR decline of >=30% (50 had doubling of serum creatinine/ESRD). In adjusted analysis, bariatric surgery patients had a significant 58% lower risk for an eGFR decline of >=30% (hazard ratio 0.42, 95% confidence interval 0.32-0.55) and 57% lower risk of doubling of serum creatinine or ESRD (hazard ratio 0.43, 95% confidence interval: 0.26-0.71) compared with the matched cohort. Results were generally consistent among subgroups of patients with and without eGFR <90 ml/min per 1.73 m(2), hypertension, and diabetes. Thus, bariatric surgery may be an option to prevent kidney function decline in severely obese individuals. PMID- 27182003 TI - Paraphilia and sex offending - A South African criminal law perspective. AB - Historically, the link between sexual deviance and criminality has been described and documented, asserted by psychiatry, and manifested in law. Laws that have regulated sexual behaviour have referred to terms such as 'sexual deviation', 'sexual perversion' or even archaic moral terms such as 'unnatural acts and unspeakable crimes against nature'. A possible link between sexual perversion, psychopathy, and criminality, specifically manifesting in sexual homicide, has been the subject of remarkable research in forensic psychiatry. This contribution examines the phenomenon of paraphilia with specific reference to its definition, diagnostic classification and characteristics, as well as a few selections of incidences of paraphilia in South African criminal case law. A brief assessment is made of how South African criminal courts have dealt with paraphilia. In this regard, an analysis is made of the criminal liability of the paraphiliac. The South African response to sexual deviation as addressed in the Criminal Law (Sexual Offences and Related Matters) Amendment Act 32 of 2007 will also be addressed with reference to its efficacy in addressing paraphilia within South African criminal law. The interface between criminal law and medical ethics within the context of this theme will also be canvassed. In conclusion, recommendations for possible reform are canvassed. PMID- 27182001 TI - The weekend effect alters the procurement and discard rates of deceased donor kidneys in the United States. AB - Factors contributing to the high rate of discard among deceased donor kidneys remain poorly understood and the influence of resource limitations of weekends on kidney transplantation is unknown. To quantify this we used data from the Scientific Registry of Transplant Recipients and assembled a retrospective cohort of 181,799 deceased donor kidneys recovered for transplantation from 2000-2013. We identified the impact of the day of the week on the procurement and subsequent utilization or discard of deceased donor kidneys in the United States, as well as report the geographic variation of the impact of weekends on transplantation. Compared with weekday kidneys, organs procured on weekends were significantly more likely to be discarded than transplanted (odds ratio: 1.16; 95% confidence interval: 1.13-1.19), even after adjusting for organ quality (adjusted odds ratio: 1.13; 95% confidence interval: 1.10-1.17). Weekend discards were of a significantly higher quality than weekday discards (Kidney Donor Profile Index: 76.5% vs. 77.3%). Considerable geographic variation was noted in the proportion of transplants that occurred over the weekend. Kidneys available for transplant over the weekend were significantly more likely to be used at larger transplant centers, be shared without payback, and experienced shorter cold ischemia times. Thus, factors other than kidney quality are contributing to the discard of deceased donor kidneys, particularly during weekends. Policy prescriptions, administrative or organizational solutions within transplant programs may potentially mitigate against the recent increase in kidney discards. PMID- 27182006 TI - A novel rabies virus lipopeptide provides a better protection by improving the magnitude of DCs activation and T cell responses. AB - Besides rabies virus neutralizing antibody, non-neutralizing antibody to internal vital proteins, interferon, and possibly cell-mediated immunity also have a critical role in preventing the infection by rabies virus (RV). We identified novel CTL and Th epitopes which could induce lymphocyte proliferation and IFN gamma, IL-4 production, and designed linear and branched lipopeptides with these selected CTL and Th epitopes. Compared to linear construct, branched lipopeptides, especially Lipo C, stimulate stronger phenotypic and functional maturation of DCs, as well as more efficient CD8(+) T cell responses, evaluating by using FACS, G333-341 tetramer staining and specific CTL assay. Lipo C could also assist rabies vaccine to induce an instant rabies virus neutralizing antibody production, and better protection against rabies virus challenge at early stage. These data reveal that Lipo C could be a promising component for developing novel rabies vaccines. PMID- 27182000 TI - Preservation of residual kidney function in hemodialysis patients: reviving an old concept. AB - Residual kidney function (RKF) may confer a variety of benefits to patients on maintenance dialysis. RKF provides continuous clearance of middle molecules and protein-bound solutes. Whereas the definition of RKF varies across studies, interdialytic urine volume may emerge as a pragmatic alternative to more cumbersome calculations. RKF preservation is associated with better patient outcomes including survival and quality of life and is a clinical parameter and research focus in peritoneal dialysis. We propose the following practical considerations to preserve RKF, especially in newly transitioned (incident) hemodialysis patients: (1) periodic monitoring of RKF in hemodialysis patients through urine volume and including residual urea clearance with dialysis adequacy and outcome markers such as anemia, fluid gains, minerals and electrolytes, nutritional, status and quality of life; (2) avoidance of nephrotoxic agents such as radiocontrast dye, nonsteroidal anti-inflammatory drugs, and aminoglycosides; (3) more rigorous hypertension control and minimizing intradialytic hypotensive episodes; (4) individualizing the initial dialysis prescription with consideration of an incremental/infrequent approach to hemodialysis initiation (e.g., twice weekly) or peritoneal dialysis; and (5) considering a lower protein diet, especially on nondialysis days. Because RKF appears to be associated with better patient outcomes, it requires more clinical and research focus in the care of hemodialysis and peritoneal dialysis patients. PMID- 27182005 TI - Single and multiple dose pharmacokinetics and pharmacodynamics of omarigliptin, a novel, once-weekly dipeptidyl peptidase-4 inhibitor, in healthy Japanese men. AB - AIMS/INTRODUCTION: Omarigliptin is a novel, potent, long-acting oral dipeptidyl peptidase-4 inhibitor being developed as a once-weekly (q.w.) treatment for type 2 diabetes mellitus patients, with 25 mg and 12.5 mg tablets recently being approved as market formulations in Japan. MATERIALS AND METHODS: This was a two part, double-blind, randomized, placebo-controlled study in healthy Japanese men to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of omarigliptin after single dose (5-100 mg) and multiple dose (1-50 mg q.w. for 3 weeks) administration. RESULTS: Omarigliptin was rapidly absorbed with a time to maximum concentration of 0.5-4 h. The pharmacokinetic profile was biphasic with a long terminal half-life >100 h. The area under the concentration-time curve from 0 to 168 h, maximum concentration and the concentration at 168 h post-dose increased dose-dependently after 3 weeks of once-weekly dosing for doses ranging 1-50 mg, with accumulation ratios ranging 1.03-1.35 and 0.87-1.36 for the area under the concentration-time curve from 0 to 168 h and maximum concentration, respectively. Plasma dipeptidyl peptidase-4 inhibition levels 1 week post-dose increased with dose, ranging 79.2-94.0% after 5-100 mg single dose administration and 51.3-90.2% after 1-50 mg multiple once-weekly dose administration. Administration with food did not meaningfully alter the pharmacokinetics of omarigliptin. Omarigliptin was generally well tolerated, with no hypoglycemia being reported. CONCLUSION: The results of the present study in healthy Japanese men showed that omarigliptin was well tolerated and had a pharmacokinetic and dipeptidyl peptidase-4 inhibition profile that supports once-weekly dosing in Japanese patients with type 2 diabetes mellitus. PMID- 27182007 TI - African swine fever virus Georgia isolate harboring deletions of 9GL and MGF360/505 genes is highly attenuated in swine but does not confer protection against parental virus challenge. AB - African swine fever virus (ASFV) produces a contagious disease of domestic pigs that results in severe economic consequences to the swine industry. Control of the disease has been hampered by the unavailability of vaccines. We recently reported the development of two experimental vaccine strains (ASFV-G-Delta9GL and ASFV-G-DeltaMGF) based on the attenuation of the highly virulent and epidemiologically relevant Georgia2007 isolate. Deletion of the 9GL gene or six genes of the MGF360/505 group produced two attenuated ASFV strains which were able to confer protection to animals when challenged with the virulent parental virus. Both viruses, although efficient in inducing protection, present concerns regarding their safety. In an attempt to solve this problem we developed a novel virus strain, ASFV-G-Delta9GL/DeltaMGF, based on the deletion of all genes deleted in ASFV-G-Delta9GL and ASFV-G-DeltaMGF. ASFV-G-Delta9GL/DeltaMGF is the first derivative of a highly virulent ASFV field strain subjected to a double round of recombination events seeking to sequentially delete specific genes. ASFV G-Delta9GL/DeltaMGF showed a decreased ability to replicate in primary swine macrophage cultures relative to that of ASFV-G and ASFV-G-DeltaMGF but similar to that of ASFV-G-Delta9GL. ASFV-G-Delta9GL/DeltaMGF was attenuated when intramuscularly inoculated into swine, even at doses as high as 10(6) HAD50. Animals infected with doses ranging from 10(2) to 10(6) HAD50 did not present detectable levels of virus in blood at any time post-infection and they did not develop detectable levels of anti-ASFV antibodies. Importantly, ASFV-G Delta9GL/DeltaMGF does not induce protection against challenge with the virulent parental ASFV-G isolate. Results presented here suggest caution towards approaches involving genomic manipulations when developing rationally designed ASFV vaccine strains. PMID- 27182009 TI - Functional analysis of ZFP36 proteins in keratinocytes. AB - The ZFP36 family of zinc finger proteins, including ZFP36, ZFP36L1, and ZFP36L2, regulates the production of growth factors and cytokines via destabilization of the respective mRNAs. We could recently demonstrate that in cultured keratinocytes, expression of the ZFP36, ZFP36L1, and ZFP36L2 genes is induced by growth factors and cytokines and that ZFP36L1 is a potent regulator of keratinocyte VEGF production. We now further analyzed the localization and function of ZFP36 proteins in the skin, specifically in epidermal keratinocytes. We found that in human epidermis, the ZFP36 protein could be detected in basal and suprabasal keratinocytes, whereas ZFP36L1 and ZFP36L2 were expressed mainly in the basal layer, indicating different and non-redundant functions of the three proteins in the epidermis. Consistently, upon inhibition of ZFP36 or ZFP36L1 expression using specific siRNAs, there was no major effect on expression of the respective other gene. In addition, we demonstrate that both ZFP36 and ZFP36L1 influence keratinocyte cell cycle, differentiation, and apoptosis in a distinct manner. Finally, we show that similarly as ZFP36L1, ZFP36 is a potent regulator of keratinocyte VEGF production. Thus, it is likely that both proteins regulate angiogenesis via paracrine mechanisms. Taken together, our results suggest that ZFP36 proteins might control reepithelialization and angiogenesis in the skin in a multimodal manner. PMID- 27182008 TI - Association between interleukin-19 and angiopoietin-2 with vascular complications in type 2 diabetes. AB - AIMS/INTRODUCTION: The aim of the present study was to investigate the role of interleukin-19 (IL-19) in angiogenesis of type 2 diabetes mellitus with complications, and to assess the relationship of serum IL-19 and angiopoietin-2 (Ang-2) in type 2 diabetes mellitus. MATERIALS AND METHODS: The group studied comprised of 240 patients with type 2 diabetes mellitus (132 men and 108 women), and included macrovascular complications, microvascular complications and type 2 diabetes mellitus without vascular complications. The control group consisted of 50 healthy blood donors. All participants were evaluated for: IL-19, Ang-2, fasting plasma glucose, fasting insulin and glycosylated hemoglobin. RESULTS: The serum IL-19 levels of type 2 diabetes mellitus patients with angiopathy were found to be significantly higher compared with patients without angiopathy. IL-19 levels were significantly positively correlated with Ang-2, homeostasis model assessment for insulin resistance and glycosylated hemoglobin (r = 0.769, 0.523 and 0.491, respectively, P < 0.01). In multivariable logistic regression analysis, IL-19 levels (P = 0.01) were found to be independently associated with patients with type 2 diabetes mellitus complications. CONCLUSIONS: These data are the first to implicate the association between the IL-19 and type 2 diabetes mellitus with vascular complications. IL-19 is significantly positively correlated with Ang-2. The potential role of IL-19 and Ang-2 in the pathogenesis of vascular complications in type 2 diabetes could warrant further study. PMID- 27182010 TI - Nasolabial pedicled compared with island flaps for intraoral reconstruction of oncological defects: complications, recovery of sensitivity, and assessment of quality of life. AB - Our aim was to compare pedicled and island nasolabial flaps used for reconstruction of oral defects in terms of postoperative complications, recovery of sensitivity, and quality of life. We organised a retrospective cohort study of 49 patients who had had intraoral reconstruction with nasolabial pedicled (n-=13) and island (n=36) flaps. Twenty- two patients filled in a validated quality-of life (QoL) questionnaire and we did sensitivity tests (sharp discrimination with the aid of a Semmes-WeinsteinTM aesthesiometer). Descriptive and bivariate statistics were computed and probabilities of 0.05 were accepted as significant. There were 11 flap-related complications (22%), and the flap was totally necrotic in three patients (6%), all of whom had island flaps. There was a significant association between flap-related complications and the use of reconstruction plate p=0.001, 95% CI 2.36 to 11.37) and advanced stage (T3 and T4 p=0.01, 95% CI 1.45 to 5.26). Skin sensitivity recovered in both island and pedicled flaps. Patients treated with island flaps had significantly more problems with prosthetic rehabilitation than those treated with pedicled flaps. The relatively low morbidity and adequate functional and aesthetic results make the pedicled nasolabial flap a viable technique. De-epithelialisation of the pedicle in island flaps permits coverage of defects with unilateral flaps in a one-stage reconstruction. However, the pedicle may be excessively stretched, leading to ischaemic complications. PMID- 27182011 TI - Biomechanical evaluation of different fixation systems after Le Fort I osteotomy in polyurethane models of unilateral clefts. AB - We compared the stability of three different titanium plate-and-screw fixation systems after Le Fort I osteotomy in polyurethane models of unilateral clefts. Thirty-six models were divided into 3 groups. In the first group, we adapted standard Plates 1mm thick with 2.0mm screws and placed them bilaterally on the zygomatic buttress and the piriform rim. In the second group, we did the same and added Plates 0.6mm thick with 1.6mm screws between the standard 2mm miniplates on both sides. In the last group, we placed Plates 1.4mm thick with 2.0mm screws bilaterally on the maxillary zygomatic buttress and piriform rim. Each group was tested in the inferosuperior (IS) and anteroposterior (AP) directions with a servo-hydraulic testing unit. In the IS direction, displacement values were not significantly different up to 80N, but between 80 and 210N, those in the 2*1.4mm group were better. In the AP direction, displacement values were not significantly different up to 40N, but between 40 and 180N, they were better in the standard with 1.6*0.6mm group and the 2*1.4mm group. When normal biting forces (90 - 260N) in the postoperative period are considered, the greatest resistance to occlusal loads was seen in the 2*1.4mm group. In the others, the biomechanical properties were better in the AP direction. PMID- 27182012 TI - Sun exposure, skin color and vitamin D status in Arab children and adults. AB - Accumulating evidence suggests an increased prevalence of vitamin D deficiency in the Middle East and North African countries. Sunlight has long been recognized as a major provider of vitamin D and lighter skin color has been associated with better vitamin D status. In this context, we aimed to determine whether 25 hydroxyvitamin D[25-(OH)D] concentrations are related to skin color, sun exposure and gender among healthy Saudi children and adults. A total of 808 Saudi children (age=14.6+/-0.04years) and 561 (age=31.4+/-0.3years) adults of both genders were included in this study. Levels of sun exposure and skin color were determined using a standard questionnaire. Anthropometry and plasma 25-(OH)D concentrations were analyzed. On the basis of duration of sun exposure (<20min vs. >20min), a significantly lower concentration of 25-(OH)D (40.9+/-1.2 vs. 35.5+/-1.8nmol/l; p<0.019) was demonstrated in dark-skinned boys with exposure time less than 20min than those exposed longer than 20min. We were unable to show an effect of sunlight exposure or skin color on vitamin D status of children or adults, except in dark-skinned boys who had lower 25(OH)D concentrations associated with limited sun exposure. PMID- 27182013 TI - Psychological and Physical Health in Family Caregivers of Intensive Care Unit Survivors: Current Knowledge and Future Research Strategies. AB - PURPOSE: This article provides an overview of current knowledge on the impact of caregiving on the psychological and physical health of family caregivers of intensive care unit (ICU) survivors and suggestions for future research. METHODS: Review of selected papers published in English between January 2000 and October 2015 reporting psychological and physical health outcomes in family caregivers of ICU survivors. RESULTS: In family caregivers of ICU survivors followed up to five years after patients' discharge from an ICU, psychological symptoms, manifested as depression, anxiety and post-traumatic stress disorder, were highly prevalent. Poor self-care, sleep disturbances and fatigue were identified as common physical health problems in family caregivers. Studies to date are mainly descriptive; few interventions have targeted family caregivers. Further, studies that elicit unique needs of families from diverse cultures are lacking. CONCLUSION: Studies to date have described the impact of caregiving on the psychological and physical health in family caregivers of ICU survivors. Few studies have tested interventions to support unique needs in this population. Therefore, evidence for best strategies is lacking. Future research is needed to identify ICU caregivers at greatest risk for distress, time points to target interventions with maximal efficacy, needs of those from diverse cultures and test interventions to mitigate family caregivers' burden. PMID- 27182014 TI - [Experience of Role Adaptation from Nurse to Member of the Nursing Faculty]. AB - PURPOSE: The purpose of this qualitative study was to evaluate the experience of role adaptation from nurse to member of the nursing faculty. METHODS: Data were collected from 13 members of a nursing faculty through in-depth interviews. The main question asked was "Could you describe your experience from being a nurse to becoming a member of the nursing faculty?" Qualitative data from the field and transcribed notes were analyzed using Strauss and Corbin's grounded theory methodology. RESULTS: The core experiential category of role adaptation from nurse to member of the nursing faculty was 'striving for survival from culture shock'. The participants used the following three interactional strategies: 'recognizing everything and entering the school environment', 'self-reflection on being a professor and integration of experiences', and 'finding a way of adapting'. CONCLUSION: The participants tried to adapt to life as a professor and reflected on and integrated their experiences into their new life on the faculty. College faculty need to understand the impact of changes and challenges faced by new professors during role adaptation and to support this adaptation through mentorship and organized orientation programs. PMID- 27182015 TI - [Development and Effects of a Drinking Prevention Program for Preschool Children]. AB - PURPOSE: The purpose of this study was to identify the effects of the program to promote drinking knowledge, attitudes, and coping behavior in preschool children. METHODS: A quasi-experimental with non-equivalent control group pretest-posttest design was conducted. The participants were 123 five year old children from G city. They were assigned to the experimental group (n=77) or the control group (n=46). A pretest and posttest were conducted to measure main variables. For the experimental group, the drinking prevention program was given for 6 weeks. Data were analyzed using chi2-test, t-test, and ANCOVA. RESULTS: After the intervention, preschool children in the experimental group reported significant differences in drinking knowledge (F=9.25, p=.003), drinking attitudes (F=19.57, p<.001), and coping behavior (F=16.38, p<.001) compared to preschool children in the control group. CONCLUSION: The results of this study indicate that a drinking prevention program for preschool children is effective in increasing drinking knowledge, attitudes, and coping behavior. This drinking prevention program is recommended as an effective intervention for preschool age children to postpone an early introduction to drinking. PMID- 27182016 TI - [The Effect of K-MBSR Program on Stress, Stress Coping Style, Depression, Anger and Sleep of Middle Aged Women]. AB - PURPOSE: The purpose of this study was to examine a Korean Mindfulness Based Stress Reduction (K-MBSR) program for middle aged women and to verify the program's effectiveness on stress, stress coping style, depression, anger and sleep. METHODS: Fifty-two women aged from 40 to 59 (26 in the experimental group and 26 in the control group) from G city participated in the study. Data were collected from February 13 to April 3, 2013. The experimental group received 8 sessions, scheduled once a week, with each session lasting two and a half hours. Outcome variables included stress, stress coping style, depression, anger, sleep and a physiological measure (EEG). RESULTS: There were significant decreases for stress (t=-2.14, p=.037), depression (t=-2.64, p=.011), state trait anger (t= 3.79, p<.001) in the experimental group compared to the control group. CONCLUSION: The findings in this study indicate that the K-MBSR program is an effective program to decrease stress, depression, and state trait anger in middle aged women. PMID- 27182017 TI - [A Validation Study of the Korean Version of the Jefferson Empathy Scale for Health Professionals for Korean Nurses]. AB - PURPOSE: To validate the Korean Version of the Jefferson Empathy Scale for Health professionals (K-JSE-HP) in a sample of Korean nurses. METHODS: Internal consistency reliability, construct and criterion validity were calculated using SPSS (22.0) and AMOS (22.0). Data were collected from 253 nurses (230 women, 23 men) working at one university hospital in Seoul, South Korea. RESULTS: The Korean version of JSE-HP showed reliable internal consistency with Cronbach's alpha for the total scale of .89, and .74~.84 for subscales. The model of three subscales for the K-JSE-HP was validated by confirmatory factor analysis (chi2=864.60, Q=6.55, p<.001, CFI=.94, NNFI=.92). Criterion validity compared to the Interpersonal Reaction Index (IRI) showed significant correlation. CONCLUSION: The findings of this study demonstrate that the Korean JSE-HP shows satisfactory construct and criterion validity and reliability. It is a useful tool to measure Korean nurses' empathy. PMID- 27182018 TI - [Life Experience following Suicide Attempt among Middle-aged Men]. AB - PURPOSE: This study was performed to identify the meaning of life experience following suicide attempt among middle-aged men. METHODS: A qualitative research design was adopted using van Manen's hermeneutic phenomenological approach. The participants were six middle-aged men who had attempted suicide at least one time. Data were collected in 2013 through in-depth interviews. Individual interviews were recorded; and literary, art works and phenomenological literature were searched to identify the meaning of the experience. RESULTS: The five essential themes of the life experience of middle-aged men who attempted suicide were 'Bitter reality confronted again', 'Anger buried deep inside', 'Broken family, inescapable fetters', 'Blocked relationships, closed world' and 'A step towards a new life'. CONCLUSION: The meaning of lived experience found in this study provides deep insight into the experience following suicide attempt in middle-aged men and crucial information to give directions to appropriate support and nursing interventions. PMID- 27182019 TI - [A Grounded Theory Approach on Nurses' Experience with Workplace Bullying]. AB - PURPOSE: The purpose of this qualitative study was to explore the workplace bullying experience of Korean nurses. METHODS: Participants were twenty current or former hospital nurses who had experienced workplace bullying. Data were collected through focus group and individual in-depth interviews from February to May, 2015. Theoretical sampling method was applied to the point of theoretical saturation. Transcribed interview contents were analyzed using Corbin and Strauss's grounded theory method. RESULTS: A total of 110 concepts, 48 sub categories, and 17 categories were identified through the open coding process. As a result of axial coding based on the paradigm model, the central phenomenon of nurses' workplace bullying experience was revealed as 'teaching that has become bullying', and the core category was extracted as 'surviving in love-hate teaching' consisting of a four-step process: confronting reality, trial and error, relationship formation, and settlement. The relationship formation was considered to be the key phase to proceed to the positive settlement phase, and the participants utilized various strategies such as having an open mind, developing human relationships, understanding each other in this phase. CONCLUSION: The in-depth understanding of the workplace bullying experience has highlighted the importance of effective communication for cultivating desirable human relationships between nurses. PMID- 27182020 TI - [Clinical Work Experience of Korean Immigrant Nurses in U.S. Hospitals]. AB - PURPOSE: The purpose of this qualitative study was to explore the meaning of the experience of Korean immigrant nurses working in US hospitals. METHODS: Purposive sampling yielded 15 Korean immigrant nurses who had more than one year of clinical experience in US hospitals. Data were collected from March to August 2012 through in-depth interviews and thematic analysis was conducted using van Manen's hermeneutic phenomenological approach. RESULTS: The findings were classified into eight themes: 'struggling from staff at workplace being territorial to outsiders', 'feeling oppressed due to language barrier', 'accepting rational and horizontal relationships at work', 'staying alert in the environment where lawsuits are rife', 'feeling a sense of stability from the social system that values human dignity', 'maintaining self-confidence from prominent nursing practices and senior Korean nurses' professional reputation', 'performing essential comprehensive nursing care', 'promoting self-development to be equipped with professionalism.' CONCLUSION: The findings indicate that the Korean immigrant nurses were able to excel in their workplace when their clinical experience at US hospitals was combined with the lived space in US politics and environment, lived time of patience, lived body to be alert, and lived others with multi cultural characteristics. PMID- 27182021 TI - [Effects of Auricular Acupressure on Obesity in Women with Abdominal Obesity]. AB - PURPOSE: The purpose of this study was to examine the effects of auricular acupressure on reducing obesity in adult women with abdominal obesity. METHODS: The study design was a non-equivalent control group pretest-posttest design. Participants were 58 women, aged 20 years or older, assigned to the experimental group (n=30) or control group (n=28). Auricular acupressure using vaccaria seeds was administered to the experimental group. The sessions continued for 8 weeks. Outcome measures included body weight, abdominal circumference, and body mass index, body fat mass, body fat percentage, triglyceride, total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, and serum glucose. RESULTS: Women in the experimental group showed significant decreases in body weight (t=6.19, p<.001), abdominal circumference (t=4.01, p<.001), and body mass index (t=2.58, p=.006) after 8 weeks compared with those in the control group. CONCLUSION: Results show that auricular acupressure using vaccaria seeds was effective in decreasing body weight, abdominal circumference, body mass index, and triglyceride levels in adult women with abdominal obesity. PMID- 27182022 TI - [Development and Application of an Overcoming Compassion Fatigue Program for Emergency Nurses]. AB - PURPOSE: This study was conducted to develop a program to help emergency nurses overcome compassion fatigue, and to analyze the effects of the program. METHODS: A nonequivalent control group pretest-posttest design was used. There were 14 participants in the experimental group and 18 subjects in the control group. The program was comprised of five, weekly 80-minute sessions including understanding and assessment of compassion fatigue, enhancing positive affect, balancing work life, planning self care, training in relaxation techniques and cognitive restructuring, and getting social support. Research variables were ego resiliency, compassion satisfaction and compassion fatigue of the ProQOL 5, and salivary cortisol. Data were analyzed using Chi-square test, independent t-test, and paired t-test. RESULTS: The first hypothesis, "There will be a difference in scores for ego resiliency between the experimental group and the control group". was not supported. The second hypothesis, "There will be a difference in scores for compassion satisfaction between the experimental group and the control group" was supported (t=2.15, p=.046). The third hypothesis, "There will be a difference in scores for compassion fatigue between the experimental group and the control group" was not supported. CONCLUSION: The first program for emergency nurses to overcome compassion fatigue in Korea was effective in increasing emergency nurses' compassion satisfaction and decreasing salivary cortisol level in the experimental group. Therefore, this program for overcoming compassion fatigue is useful to increase emergency nurses' compassion satisfaction. However replication studies of short-term intensive program reflecting emergency nurses' opinion are needed. PMID- 27182023 TI - [Adaptation Experience of Living Kidney Donors after Donation]. AB - PURPOSE: This study was done to explore adaptation experience of living kidney donors after donation. Specific aims were to identify challenges donors face in the process of adaptation following surgery and how they interact with recipients and other people. METHODS: Grounded theory methodology was utilized. Participants were 13 living kidney donors at six months or more after donation. Data were collected by in-depth interviews with individual participants. Data were analyzed using constants comparative method with theoretical saturation. RESULTS: A core category emerged as 'keeping the fences of my family in spite of vulnerability'. The adaptation process after donation was manifested in four phases: exploration, balance, maintenance, and acclimatization. Phenomenon was perception of vulnerability. Strategies to manage the vulnerability were assessing changes of body awareness, tailoring regimen to one's own body condition, coping with health problems, keeping restoration of health, and ruminating on the meaning of one's kidney donation. Consequences were reestablishing family well-being, realizing the values of one's kidney donation, and living with uncertainty. CONCLUSION: Findings of the study indicate that there is a need for health professionals to understand the vulnerability of living kidney donors and help their family system maintain a healthy and productive life. The results of this study can be used to develop phase-specific, patient-centered, and tailored interventions for living kidney donors. PMID- 27182024 TI - [Effects of Self-directed Feedback Practice using Smartphone Videos on Basic Nursing Skills, Confidence in Performance and Learning Satisfaction]. AB - PURPOSE: This study was done to verify effects of a self-directed feedback practice using smartphone videos on nursing students' basic nursing skills, confidence in performance and learning satisfaction. METHODS: In this study an experimental study with a post-test only control group design was used. Twenty nine students were assigned to the experimental group and 29 to the control group. Experimental treatment was exchanging feedback on deficiencies through smartphone recorded videos of nursing practice process taken by peers during self directed practice. RESULTS: Basic nursing skills scores were higher for all items in the experimental group compared to the control group, and differences were statistically significant ["Measuring vital signs" (t=-2.10, p=.039); "Wearing protective equipment when entering and exiting the quarantine room and the management of waste materials" (t=-4.74, p<.001) "Gavage tube feeding" (t=-2.70, p=.009)]. Confidence in performance was higher in the experimental group compared to the control group, but the differences were not statistically significant. However, after the complete practice, there was a statistically significant difference in overall performance confidence (t=-3.07. p=.003). Learning satisfaction was higher in the experimental group compared to the control group, but the difference was not statistically significant (t=-1.67, p=.100). CONCLUSION: Results of this study indicate that self-directed feedback practice using smartphone videos can improve basic nursing skills. The significance is that it can help nursing students gain confidence in their nursing skills for the future through improvement of basic nursing skills and performance of quality care, thus providing patients with safer care. PMID- 27182025 TI - [Development and Psychometric Evaluation of the Transcultural Self-efficacy Scale for Nurses]. AB - PURPOSE: This methodological study was conducted to develop and psychometrically test the Transcultural Self-efficacy scale (TCSEscale) for nurses. METHODS: Initial 41 items for the TCSE-scale were generated based on extensive literature reviews and in-depth interviews with 18 nurses who had experience in caring for foreign patients. Cultural Competence and Confidence model was used as a conceptual framework. Content validity was evaluated by an expert panel. Psychometric testing was performed with a convenience sample of 242 nurses recruited from four general hospitals in the Seoul metropolitan area and Gyeonggi do province of South Korea. To evaluate the reliability of TCSE-scale, a test retest reliability and an internal consistency reliability were analyzed. Construct validity, concurrent validity, criterion validity, convergent validity and discriminative validity were used to evaluate the validity. RESULTS: The 25 item TCSE-scale was found to have three subscales-Cognitive, Practical, and Affective domain-explaining 91.5% of the total variance. TCSE-scale also demonstrated a concurrent validity with the Cultural Competence Scale. Criterion related validity was supported by known-group comparison. Reliability analysis showed an acceptable-to-high Cronbach's alpha-.88 in total, and subscales ranged from .76 to .87. The ICC was .90, indicating that the TCSE-scale has internal consistency and stability of reliability. CONCLUSION: This preliminary evaluation of the psychometric scale properties demonstrated an acceptable validity and reliability. The TCSE-scale is able to contribute to building up empirical and evidence based on data collection regarding the transcultural self-efficacy of clinical nurses. We suggest further testing of the applicability of TCSE-scale in different settings and community contexts. PMID- 27182026 TI - [Factors Influencing Quality of Life of Alcoholics Anonymous Members in Korea]. AB - PURPOSE: The purpose of this study was to determine quality of life (QOL) related factors in Alcoholics Anonymous (AA) members based on PRECEDE Model. METHODS: A cross sectional survey was conducted with participants (N =203) from AA meeting in 11 alcohol counsel centers all over South Korea. Data were collected using a specially designed questionnaire based on the PRECEDE model and including QOL, epidemiological factors (including depression and perceived health status), behavioral factors (continuous abstinence and physical health status and practice), predisposing factors (abstinence self-efficacy and self-esteem), reinforcing factors (social capital and family functioning), and enabling factors. Data were analyzed using t-test, one way ANOVA, Tukey HSD test and hierarchical multiple regression analysis with SPSS (ver. 21.0). RESULTS: Of the educational diagnostic variables, self-esteem (beta=.23), family functioning (beta=.12), abstinence self-efficacy (beta=.12) and social capital (beta=.11) were strong influential factors in AA members' QOL. In addition, epidemiological diagnostic variables such as depression (beta=-.44) and perceived health status (beta=.35) were the main factors in QOL. Also, physical health status and practice (beta=.106), one of behavioral diagnostic variables was a beneficial factor in QOL. Hierarchical multiple regression analysis showed the determinant variables accounted for 44.0% of the variation in QOL (F=25.76, p<.001). CONCLUSION: The finding of the study can be used as a framework for planning interventions in order to promote the quality of life of AA members. It is necessary to develop nursing intervention strategies for strengthening educational and epidemiological diagnostic variables in order to improve AA members' QOL. PMID- 27182027 TI - Switching the regioselectivity in the copper-catalyzed synthesis of iodoimidazo[1,2-a]pyridines. AB - A unique copper-catalyzed binucleophilic switching of 2-aminopyridine has been developed for the regioselective synthesis of 2- and 3-iodoimidazo[1,2 a]pyridines using alkenes/alkynes as coupling partners in the presence of molecular iodine under aerobic reaction conditions. This method was also applied to the synthesis of 2-iodo-3-phenylbenzo[d]imidazo[2,1-b]thiazoles. This protocol offers an easy route towards the synthesis of 2,3-diarylimidazo[1,2-a]pyridines. PMID- 27182029 TI - Blood lactate concentration after cardiac arrest resulting from myocardial infarction and outcome. PMID- 27182030 TI - Intravenous Home Infusion Therapy Instituted From a 24-Hour Clinical Decision Unit For Patients With Cellulitis. AB - OBJECTIVES: The objective of the study is to evaluate whether patients with cellulitis can be safely discharged from a 24-hour clinical decision unit (CDU) with home infusion of intravenous (IV) antibiotics. METHODS: Clinical decision unit patients receiving IV antibiotics for cellulitis were screened for enrollment in a home infusion therapy (HIT) program. Inclusion criteria were patient ability and willingness to administer IV antibiotics at home and insurers' approval of home infusion services. Patients were discharged home with a peripheral IV and care coordinated with a home infusion provider. RESULTS: Of 213 patients with cellulitis transferred from the emergency department to the CDU over an 8-month study period, a total of 32 (15%) were discharged from the CDU with HIT. The average duration of home IV antibiotic treatment was 3.4 days. There were a total of 9 complications (28%), including IV infiltration (n = 5), allergic reactions (n = 2), nontolerance to the antibiotic (n = 1, this patient developed severe nausea and was switched to oral antibiotics after 2 days of HIT), and 1 patient required readmission for lack of clinical improvement. Among the 181 patients with cellulitis who did not receive HIT, 39 (22%) were hospitalized from the CDU, and 1 additional patient refused admission. CONCLUSIONS: We avoided admission for 31 (97%) of 32 patients who were enrolled in HIT. Home infusion therapy has the potential to prevent hospitalizations, alleviate overcrowding of hospital beds, and decrease health care costs. Further studies are needed to determine the full impact of HIT on CDU patients with acute cellulitis. PMID- 27182032 TI - Gold coated magnetic nanoparticles: from preparation to surface modification for analytical and biomedical applications. AB - Gold coated magnetic nanoparticles (Au@MNPs) have become increasingly interesting to nanomaterial scientists due to their multifunctional properties and their potential in both analytical chemistry and nanomedicine. The past decade has seen significant progress in the synthesis and surface modification of Au@MNPs. This progress is based on advances in the preparation and characterization of iron/iron oxide nanocrystals with the required surface functional groups. In this critical review, we summarize recent developments in the methods of preparing Au@MNPs, surface functionalization and their application in analytical sensing and biomedicine. We highlight some of the remaining major challenges, as well as the lessons learnt when working with Au@MNPs. PMID- 27182031 TI - Efficacy and safety of once-daily insulin degludec dosed flexibly at convenient times vs fixed dosing at the same time each day in a Japanese cohort with type 2 diabetes: A randomized, 26-week, treat-to-target trial. AB - AIMS/INTRODUCTION: This trial assessed the efficacy and safety of the possibility of varying the daily injection time of once-daily, long-acting basal insulin degludec (IDeg) in Japanese patients with type 2 diabetes inadequately controlled with insulin glargine. MATERIALS AND METHODS: This was a 26-week, multicenter, open-label, randomized, treat-to-target trial, with a 2 * 2 factorial design comparing IDeg flexible (allowing dosing +/-8 h from an agreed dosing time) with IDeg fixed dosing (at the same time each day). It was carried out in 458 adult patients who were inadequately controlled on insulin glargine with or without oral antidiabetic drugs. RESULTS: The majority of doses were taken within 2 h of the agreed dosing time, showing a high level of adherence among Japanese patients. After 26 weeks, IDeg flexible was non-inferior to IDeg fixed with respect to change in glycated hemoglobin from baseline, estimated treatment difference 0.08% points (95% confidence interval -0.05; 0.22). Fasting plasma glucose decreased to a similar level with IDeg flexible and IDeg fixed, estimated treatment difference -0.18 mmol/L (95% confidence interval -0.48; 0.12). The rates of confirmed and nocturnal confirmed hypoglycemia were numerically, but not significantly, higher with IDeg flexible vs IDeg fixed dosing. The rates of adverse events with IDeg flexible and IDeg fixed dosing were similar. CONCLUSIONS: These results showed the efficacy and safety of allowing patients to vary the time they dosed IDeg, when necessary, in Japanese patients with type 2 diabetes. Dosing of IDeg at a time convenient to the patient was non-inferior, with respect to glycated hemoglobin, to dosing at the same time each day. PMID- 27182033 TI - Adherence to dipeptidyl peptidase-4 inhibitor therapy among type 2 diabetes patients with employer-sponsored health insurance in Japan. AB - AIMS/INTRODUCTION: Dipeptidyl peptidase-4 inhibitors (DPP-4i) are a common first line treatment for type 2 diabetes in Japan. However, little is known about patients' medication adherence, persistence and discontinuation in this setting. MATERIALS AND METHODS: This was a retrospective cohort study of new DPP-4i users in a Japanese claims database. Adult patients (age 18-65 years) with type 2 diabetes diagnosis and no diagnosis of other diabetes or pregnancy during the study period were included if they were prescribed a DPP-4i as monotherapy or combination oral therapy. Adherence to therapy was measured using the proportion of days covered method over a fixed period of 1 year. The proportion of days covered of >=80% was considered adherent. Persistence was defined as continuing index DPP-4i treatment with <90-day gap between refills. Patient baseline characteristics were explored as potential predictors of DPP-4i discontinuation and adherence in multivariable models. RESULTS: The final sample contained 2,874 monotherapy and 3,016 dual therapy patients. The mean age was approximately 51 years, and 75% were men. The mean proportion of days covered was 76.6% among monotherapy patients and 82.5% among dual therapy patients, with 67.2% of monotherapy and 74.4% of dual therapy patients classified as adherent. At 12 months, 72.2% of monotherapy and 79.2% of dual therapy patients were persistent. In adjusted models, younger age and having fewer concomitant medications were significantly associated with lower adherence and higher discontinuation, in both treatment groups. CONCLUSIONS: Those under the age of 45 years, and those with fewer concomitant medications were less likely to be adherent and persistent, and more likely to discontinue DPP-4i therapy. PMID- 27182034 TI - Investigating the potential for cryopreservation of human granulocytes with concentrated glycerol. AB - The purpose of this study was to investigate the potential for cryopreservation of granulocytes using 30% glycerol. Recently reported permeability data was used to design two different methods for addition and removal of glycerol: a fast method that is predicted to keep cell volumes between 80% and 150% of the isotonic volume and a slow method that is predicted to keep cell volumes between 80% and 115% of the isotonic volume. The fast method resulted in cell recoveries of 31% +/- 9% and 11% +/- 3% before and after freezing, respectively, whereas the slow method resulted in even lower cell recoveries of 5% +/- 2% and 4% +/- 2%. The reduced cell recovery for the slow method is consistent with an increase in damage as a result of glycerol toxicity. Our results suggest that cryopreservation of granulocytes in concentrated glycerol is not feasible. PMID- 27182035 TI - Beyond membrane integrity: Assessing the functionality of human umbilical vein endothelial cells after cryopreservation. AB - Assessment of cell membrane integrity is one of the most widely used methods to measure post-cryopreservation viability of cells such as human umbilical vein endothelial cells (HUVECs). However, an evaluation of cell function provides a better measure of cell quality following cryopreservation. The tube formation assay mimics angiogenesis in vitro and can be used to quantitate the ability of endothelial cells to form capillary-like tubular structures when cultured on reconstituted basement membrane (Matrigel). We compared the membrane integrity (measured by flow cytometry) and tube forming ability of HUVEC suspensions exposed to 10% dimethyl sulfoxide (Me2SO), cooled at 1 degrees C/min to various sub-zero temperatures, plunged directly into liquid nitrogen, stored for an hour, and thawed rapidly. We found that as membrane integrity increased so did the various parameters associated with the extent of in vitro angiogenesis; however, in comparison to fresh cells with a similar percentage of membrane-intact cells, the extent of tube formation, expressed as total tube length, is significantly lower in previously frozen cells for the lower range of post-thaw membrane integrities. Our findings underscore the value of an assay that quantifies a specific function that a cell is known to perform in vivo to measure the success of cryopreservation protocols. PMID- 27182036 TI - Can Vascular Patterns on Preoperative Magnetic Resonance Imaging Help Predict Skin Necrosis after Nipple-Sparing Mastectomy? AB - BACKGROUND: Nipple-areola complex (NAC) and skin flap ischemia and necrosis can occur after nipple-sparing mastectomy (NSM). The purpose of this study was to correlate vascular findings on MRI with outcomes in patients who underwent NSM. STUDY DESIGN: Female patients at a single institution who underwent NSM and had a preoperative breast MRI between 2010 and 2014 were identified. Medical records were reviewed for patient demographics, surgical factors, and complications. Magnetic resonance images were reviewed by 2 radiologists, blinded to outcomes, for the presence of dual vs single blood supply to the breast. The association between blood supply on MRI with ischemic and necrotic complications after NSM was analyzed. RESULTS: One hundred and sixty-four NSM procedures were performed in 105 patients (mean age 45.5 years, range 25 to 69 years) who had a preoperative MRI. The majority of procedures were performed for malignancy (89 of 164 [54.3%]) or prophylaxis (73 of 164 [44.5%]). Nipple-areola complex or skin flap ischemia or necrosis occurred in 40 (24.4%) breasts. Ischemia or necrosis after NSM was less likely to occur in breasts with dual compared with single blood supply (20.8% vs 38.2%; p = 0.03). There was no association between surgical complications and age, BMI, smoking history, previous radiation therapy, indication for NSM, surgical specimen weight, surgical incision type, reconstruction approach, or operating surgeon on univariate analysis. CONCLUSIONS: Preoperative MRI characterization of breast vascularity can be considered when planning NSM. The presence of a dual blood supply to the breast on MRI is associated with a decreased risk of nipple-areola complex and skin flap ischemia and necrosis after NSM. PMID- 27182037 TI - Emotional Intelligence as a Predictor of Resident Well-Being. AB - BACKGROUND: There is increasing recognition that physician wellness is critical; it not only benefits the provider, but also influences quality and patient care outcomes. Despite this, resident physicians suffer from a high rate of burnout and personal distress. Individuals with higher emotional intelligence (EI) are thought to perceive, process, and regulate emotions more effectively, which can lead to enhanced well-being and less emotional disturbance. This study sought to understand the relationship between EI and wellness among surgical residents. STUDY DESIGN: Residents in a single general surgery residency program were surveyed on a voluntary basis. Emotional intelligence was measured using the Trait Emotional Intelligence Questionnaire-Short Form. Resident wellness was assessed with the Dupuy Psychological General Well-Being Index, Maslach Burnout Inventory, and Beck Depression Inventory-Short Form. Emotional intelligence and wellness parameters were correlated using Pearson coefficients. Multivariate analysis was performed to identify factors predictive of well-being. RESULTS: Seventy-three residents participated in the survey (response rate 63%). Emotional intelligence scores correlated positively with psychological well-being (r = 0.74; p < 0.001) and inversely with depression (r = -0.69, p < 0.001) and 2 burnout parameters, emotional exhaustion (r = -0.69; p < 0.001) and depersonalization (r = -0.59; p < 0.001). In regression analyses controlling for demographic factors such as sex, age, and relationship status, EI was strongly predictive of well-being (beta = 0.76; p < 0.001), emotional exhaustion (beta = 0.63; p < 0.001), depersonalization (beta = -0.48; p = 0.002), and depression (beta = -0.60; p < 0.001). CONCLUSIONS: Emotional intelligence is a strong predictor of resident well-being. Prospectively measuring EI can identify those who are most likely to thrive in surgical residency. Interventions to increase EI can be effective at optimizing the wellness of residents. PMID- 27182038 TI - Photoinduced electron transfer in porous organic salt crystals impregnated with fullerenes. AB - Porous organic salt (POS) crystals composed of 9-(4-sulfophenyl)anthracene (SPA) and triphenylmethylamine (TPMA) were impregnated with fullerenes (C60 and C70), which were arranged in one dimensional close contact. POS crystals of SPA and TPMA without fullerenes exhibit blue fluorescence due to SPA, whereas the fluorescence was quenched in POS with fullerenes due to electron transfer from the singlet excited state of SPA to fullerenes. PMID- 27182039 TI - A novel mutation in FBXL4 in a Norwegian child with encephalomyopathic mitochondrial DNA depletion syndrome 13. AB - Mitochondrial DNA depletion syndromes (MTDPS) represent a clinically and genetically heterogeneous group of autosomal recessive disorders, caused by mutations in genes involved in maintenance of mitochondrial DNA (mtDNA). Biallelic mutations in FBXL4 were recently described to cause encephalomyopathic MTDPS13. The syndrome has infantile onset and presents with hypotonia, feeding difficulties, a pattern of mild facial dysmorphisms, global developmental delay and brain atrophy. Laboratory investigations reveal elevated blood lactate levels, unspecific mitochondrial respiratory chain (MRC) enzyme deficiencies and mtDNA depletion. We report a novel missense variant, c.1442T > C (p.Leu481Pro), in FBXL4 (NM_012160.4) in a Norwegian boy with clinical, biochemical and cerebral MRI characteristics consistent with MTDPS13. The FBXL4 c.1442T > C (p.Leu481Pro) variant was not present in public databases, 149 Norwegian controls nor an in house database containing whole exome sequencing data from 440 individuals, and it was predicted in silico to be deleterious to the protein function. Activities of MRC enzymes were normal in muscle tissue (complexes I-IV) and cultured skin fibroblasts (complexes I-V) from the patient, but mtDNA depletion was confirmed in muscle, thus supporting the predicted pathogenicity of the FBXL4 c.1442T > C (p.Leu481Pro) variant. On clinical indication of mitochondrial encephalomyopathy, sequencing of FBXL4 should be performed, even when the activity levels of the MRC enzymes are normal. PMID- 27182040 TI - A novel ACVR1 mutation detected by whole exome sequencing in a family with an unusual skeletal dysplasia. AB - "Disorganized Development of Skeletal Component" (DDSC) is a group of genetic skeletal dysplasia, caused by mutations in 9 genes including ACVR1. The most known ACVR1-related disorder is fibrodysplasia ossificans progressiva (FOP). FOP variants are frequently encountered with diagnostic challenges due to overlapping clinical manifestations and variable severity. Application of high throughput sequencing methods can overcome these limitations by simultaneous investigation of the entire ACVR1 gene together with other genes involved in disorders with similar manifestations. A 33-year-old man with an unusual skeletal dysplasia and no previous clinical diagnosis is presented in this study. Whole exome sequencing detected a novel c.737T>A (p.Phe246Tyr) mutation in ACVR1 gene. Detailed targeted variant analysis in 226 known genes associated with genetic skeletal disorders together with more specific targeted analysis in 9 genes associated with DDSC ruled out the involvement of other investigated genes. Proband's phenotypically normal father and brother had the same mutation in whom subsequent investigations showed subclinical radiographic findings. The clinical manifestations, the disease course, and the molecular findings of involvement of ACVR1 gene in this family are suggestive of "FOP variant" or an unusual ACVR1-related skeletal dysplasia. Moreover, this report has demonstrated the critical role of the next generation sequencing technique in characterizing such a rare disorder with variable and even no clinical manifestations, providing the opportunity for effective preventive measures such as preimplantation genetic diagnosis. PMID- 27182041 TI - Urinary adiponectin and progression of diabetic nephropathy in type 1 diabetes. AB - The complex role of adiponectin in diabetic nephropathy. PMID- 27182042 TI - Combination therapy with liraglutide and insulin in Japanese patients with type 2 diabetes: A 36-week, randomized, double-blind, parallel-group trial. AB - AIMS/INTRODUCTION: To assess efficacy and safety of liraglutide in combination with insulin compared with insulin monotherapy in Japanese patients with type 2 diabetes. MATERIALS AND METHODS: This was a 36-week, multicenter, double-blind, parallel-group trial, where patients on stable insulin therapy (basal/premixed/basal-bolus) were randomized 1:1 to additional liraglutide 0.9 mg/day (n = 127) or placebo (n = 130). The insulin dose was fixed for 16 weeks, and titrated based on self-measured plasma glucose thereafter. The primary end point was change in glycosylated hemoglobin after 16 weeks. RESULTS: Superiority of liraglutide plus insulin versus insulin monotherapy was confirmed based on estimated mean difference in glycosylated hemoglobin after 16 weeks of -1.30% ( 14 mmol/mol; 95% confidence interval -1.47 to -1.13 [-16, -12]; P < 0.0001). Statistical significance was maintained to week 36. More patients on liraglutide achieved a glycosylated hemoglobin target of <7.0% (<53 mmol/mol) at week 16 (estimated odds ratio 50.57; 95% confidence interval 16.59 to 154.16; P < 0.0001). Improvements in seven-point self-measured plasma glucose and fasting plasma glucose were significantly greater with liraglutide than the placebo at week 16. Insulin dose after 36 weeks was lower with liraglutide than the placebo (estimated treatment ratio: 0.82 [95% confidence interval 0.76-0.90; P < 0.0001]). Occurrence of adverse events was similar in the two groups (85.8 and 81.5%, respectively); most were mild in severity. There were no significant differences in the number of hypoglycemic episodes during the 36 weeks. CONCLUSIONS: Adding liraglutide to insulin results in superior glycemic control compared with insulin alone in Japanese patients with type 2 diabetes, and is generally well tolerated. PMID- 27182045 TI - A global portrait of the manganese industry-A socioeconomic perspective. AB - In 2013/14, Risk & Policy Analysts Ltd undertook the first global study on the socio-economic value of Manganese (Mn). Based on a top-down analysis of the key supply chains for Mn, it outlined the economic importance of Mn ore and alloys in terms of their direct and indirect economic value, as well as their effects on employment (jobs and wages). In 2013, global production of Mn ore was worth an estimated US$ 10.2-11.1 billion. Taking into account multiplier effects in the supply chain, the total economic value of Mn ore production globally in 2013 is estimated at US$ 21-23 billion. Direct employment related to Mn ore production is estimated at 44,000-78,000 people worldwide (with total wages estimated at US$ 2.7-4.6 billion per year), plus 33,000-59,000 jobs are created through indirect and induced employment effects. Meanwhile, the production of Mn alloy contributes around US$ 23 billion per year to the global economy (based on global production of around 19 million mt and 2013 market prices). In total, the value of Mn alloy production worldwide, taking into account downstream multiplier effects in the supply chain, is estimated at around US$ 146 billion per year. Direct employment related to Mn alloy production is estimated at 67,000-86,000 jobs worldwide (with total wages estimated at US$ 613-796 million per year), plus 217,000-278,000 jobs created through indirect & induced employment effects. In addition, numerous industries/sectors, products and/or applications are heavily dependent on Mn production and use. Mn is a critical raw material input and alloying element for the steel industry, for which there are no known alternatives. It can be argued that without Mn the entire steel industry (based on the current physico-chemical properties of steel) would not exist and, as a result, the value of the steel industry - an estimated US$ 964 billion to US$ 1446 billion in 2013 - is reliant on the continued supply and use of Mn. Besides its use in steel, Mn is also a critical element in the manufacture of dry cell and other batteries (notably, those used in electric vehicles) and the production of aluminium alloys (e.g. for beverage cans). Mn is also a micronutrient needed for plant growth and plays a vital role in agricultural production. It is also essential for maintaining the health and well-being of the human body and is used in food supplements and medicines. Furthermore, its use in developing applications (such as advanced steel products in automotive applications and batteries for electric vehicles) has the potential to provide socio-economic and environmental benefits in the future through enhancing vehicle safety and reducing fuel use/emissions. PMID- 27182043 TI - Increased visceral adiposity with normal weight is associated with the prevalence of non-alcoholic fatty liver disease in Japanese patients with type 2 diabetes. AB - AIMS/INTRODUCTION: To investigate the impact of increased visceral adiposity with normal weight (OB[-]VA[+]) on the prevalence of non-alcoholic fatty liver disease in patients with type 2 diabetes. MATERIALS AND METHODS: This was a cross sectional study of 140 Japanese patients with type 2 diabetes (mean age 65 +/- 11 year; 44.6% women). Visceral fat area (VFA; cm(2) ) and liver attenuation index (LAI) were assessed by abdominal computed tomography. The patients were divided into four groups by VFA and body mass index (BMI; kg/m(2) ) as follows: BMI <25 kg/m(2) and VFA <100 cm(2) (OB[-]VA[-]), BMI >=25 kg/m(2) and VFA <100 cm(2) (OB[+]VA[-]), BMI <25 kg/m(2) and VFA >=100 cm(2) (OB[-]VA[+]), and BMI >=25 kg/m(2) and VFA >=100 cm(2) (OB[+]VA[+]). Multivariate linear regression and logistic regression analysis were carried out to determine the impact of OB( )VA(+) on LAI. RESULTS: In the present study, 25.0% were OB(-)VA(+) patients, where the LAI levels were lower (1.09 +/- 0.22) than those in OB(-)VA(-) patients (1.23 +/- 0.15), and were equivalent to those in OB(+)VA(+) patients (1.03 +/- 0.26). In multivariate linear regression analysis, OB(-)VA(+) was independently associated with LAI (standardized beta-0.212, P = 0.014). In multivariate logistic regression analysis, OB(-)VA(+) was a significant predictor of LAI <0.9 (odds ratio 5.88, 95% confidence interval 1.03-33.52, P = 0.046). CONCLUSIONS: The present study provides evidence that increased visceral adiposity with normal weight is a strong predictor for the prevalence of non-alcoholic fatty liver disease in Japanese patients with type 2 diabetes. PMID- 27182044 TI - MPTP neurotoxicity is highly concordant between the sexes among BXD recombinant inbred mouse strains. AB - Continuing our previous work in which we showed wide-ranging strain differences in MPTP neurotoxicity in male mice among ten BXD recombinant inbred strains, we replicated our work in females from nine of the same strains. Mice received a single s.c. injection of 12.5mg/kg MPTP or saline. Forty-eight hours later the striatum was dissected for neurochemical analysis. Striatal dopamine (DA) and its metabolites, DOPAC and HVA, striatal serotonin (5-HT) and its metabolite, 5-HIAA, were analyzed using HPLC. Tyrosine hydroxylase (TH) and glial fibrillary acidic protein (GFAP), an astrocytic protein that increases during the astroglial response to neural injury, were measured using ELISA. There were wide genetic variations in the DA, DOPAC, HVA, TH and GFAP responses to MPTP. We also performed principal component analysis (PCA) on the difference values, saline minus MPTP, for DA, DOPAC, HVA and TH and mapped the dominant principal component to a suggestive QTL on chromosome 1 at the same location that we observed previously for males. Moreover, there were significant correlations between the sexes for the effect of MPTP on DA, HVA, and TH. Our findings suggest that the systems genetic approach as utilized here can help researchers understand the role of sex in individual differences. The same approach can pave the way to understand and pinpoint the genetic bases for individual differences in pathology attributable to toxicants. Such systems genetics approach has broad implications for elucidating gene-environment contributions to neurodegenerative diseases. PMID- 27182046 TI - Estrogen and insulin transport through the blood-brain barrier. AB - Obesity is associated with insulin resistance and reduced transport of insulin through the blood-brain barrier (BBB). Reversal of high-fat diet-induced obesity (HFD-DIO) by dietary intervention improves the transport of insulin through the BBB and the sensitivity of insulin in the brain. Although both insulin and estrogen (E2), when given alone, reduce food intake and body weight via the brain, E2 actually renders the brain relatively insensitive to insulin's catabolic action. The objective of these studies was to determine if E2 influences the ability of insulin to be transported into the brain, since the receptors for both E2 and insulin are found in BBB endothelial cells. E2 (acute or chronic) was systemically administered to ovariectomized (OVX) female rats and male rats fed a chow or a high-fat diet. Food intake, body weight and other metabolic parameters were assessed along with insulin entry into the cerebrospinal fluid (CSF). Acute E2 treatment in OVX female and male rats reduced body weight and food intake, and chronic E2 treatment prevented or partially reversed high-fat diet-induced obesity. However, none of these conditions increased insulin transport into the CNS; rather, chronic E2 treatment was associated less-effective insulin transport into the CNS relative to weight matched controls. Thus, the reduction of brain insulin sensitivity by E2 is unlikely to be mediated by increasing the amount of insulin entering the CNS. PMID- 27182048 TI - Current challenges in the surgical management of Crohn's disease: a systematic review. AB - BACKGROUND: Crohn's disease is a chronic inflammatory disorder, and the broad variability in phenotypic presentations makes the treatment of this disease a true multidisciplinary approach. We sought to review the current recommendations regarding the surgical management of Crohn's disease. DATA SOURCE: A Systematic literature review of surgical techniques was performed from 1979 through 2015. We evaluated 30 articles focusing on findings over the past 5 years. CONCLUSIONS: Crohn's is a complex disease with no surgical cure. Invasive techniques vary from strictureplasty to resection and percutaneous drainage of penetrating disease when indicated. There is a paucity of well-controlled randomized studies evaluating these surgical techniques, and therefore, we continue to rely on smaller studies and historical data. The surgical goals are to minimize postoperative complications while preserving intestinal length and slowing the progression to clinical recurrence. The evidence discussed is one strategy against this complex pathology. PMID- 27182049 TI - Non-vitamin K antagonist oral anticoagulant reversal: hope is on the horizon. AB - BACKGROUND: Non-vitamin K oral anticoagulants have become an attractive alternative to warfarin when patients require anticoagulation. Until recently, one of the biggest challenges to these agents was the lack of specific reversal of their anticoagulation when bleeding occurs or urgent/emergent procedures are required. DATA SOURCES: This article is a narrative review of peer-reviewed publications with particular attention to authors that are experts in the field, society guidelines, and government publications. CONCLUSIONS: Development of several drugs has led to agent-specific reversal. Idarucizumab has gained approval in the United States for reversal of dabigatran. Andexanet alfa has completed promising phase III trials for the reversal of factor Xa inhibitors. Aripazine (PER977) has shown promise as a universal reversal agent against non vitamin K antagonist oral anticoagulants and heparin products. PMID- 27182050 TI - Selection of a potential diagnostic biomarker for HIV infection from a random library of non-biological synthetic peptoid oligomers. AB - Non-biological synthetic oligomers can serve as ligands for antibodies. We hypothesized that a random combinatorial library of synthetic poly-N-substituted glycine oligomers, or peptoids, could represent a random "shape library" in antigen space, and that some of these peptoids would be recognized by the antigen binding pocket of disease-specific antibodies. We synthesized and screened a one bead one compound combinatorial library of peptoids, in which each bead displayed an 8-mer peptoid with ten possible different amines at each position (10(8) theoretical variants). By screening one million peptoid/beads we found 112 (approximately 1 in 10,000) that preferentially bound immunoglobulins from human sera known to be positive for anti-HIV antibodies. Reactive peptoids were then re synthesized and rigorously evaluated in plate-based ELISAs. Four peptoids showed very good, and one showed excellent, properties for establishing a sero-diagnosis of HIV. These results demonstrate the feasibility of constructing sero-diagnostic assays for infectious diseases from libraries of random molecular shapes. In this study we sought a proof-of-principle that we could identify a potential diagnostic antibody ligand biomarker for an infectious disease in a random combinatorial library of 100 million peptoids. We believe that this is the first evidence that it is possible to develop sero-diagnostic assays - for any infectious disease - based on screening random libraries of non-biological molecular shapes. PMID- 27182047 TI - Stress-induced alterations in estradiol sensitivity increase risk for obesity in women. AB - The prevalence of obesity in the United States continues to rise, increasing individual vulnerability to an array of adverse health outcomes. One factor that has been implicated causally in the increased accumulation of fat and excess food intake is the activity of the limbic-hypothalamic-pituitary-adrenal (LHPA) axis in the face of relentless stressor exposure. However, translational and clinical research continues to understudy the effects sex and gonadal hormones and LHPA axis dysfunction in the etiology of obesity even though women continue to be at greater risk than men for stress-induced disorders, including depression, emotional feeding and obesity. The current review will emphasize the need for sex specific evaluation of the relationship between stress exposure and LHPA axis activity on individual risk for obesity by summarizing data generated by animal models currently being leveraged to determine the etiology of stress-induced alterations in feeding behavior and metabolism. There exists a clear lack of translational models that have been used to study female-specific risk. One translational model of psychosocial stress exposure that has proven fruitful in elucidating potential mechanisms by which females are at increased risk for stress-induced adverse health outcomes is that of social subordination in socially housed female macaque monkeys. Data from subordinate female monkeys suggest that increased risk for emotional eating and the development of obesity in females may be due to LHPA axis-induced changes in the behavioral and physiological sensitivity of estradiol. The lack in understanding of the mechanisms underlying these alterations necessitate the need to account for the effects of sex and gonadal hormones in the rationale, design, implementation, analysis and interpretation of results in our studies of stress axis function in obesity. Doing so may lead to the identification of novel therapeutic targets with which to combat stress-induced obesity exclusively in females. PMID- 27182051 TI - The altered microRNA profile in andrographolide-induced inhibition of hepatoma tumor growth. AB - BACKGROUND: MicroRNAs (miRNAs) have been reported to play critical roles in regulating gene expression in tumor development. Natural compound andrographolide (Andro), isolated from medicinal herb Andrographis paniculata, was reported to inhibit hepatoma tumor growth in our previous studies. The present study aims to observe the altered miRNAs profile and related signaling pathways involved in Andro-induced inhibition on hepatoma tumor growth. RESULTS: The inhibition on hepatoma tumor growth induced by Andro (10mg/kg) was found in a xenograft mouse tumor model in vivo. The results of miRNAs chip analysis showed that the expression of 22 miRNAs was increased, whereas the expression of other 10 miRNAs was decreased after Andro treatment. Further, the increased expression of miR-222 3p, miR-106b-5p, miR-30b-5p, and miR-23a-5p was confirmed in hepatoma Hep3B and SMCC7721 cells in vitro after cells were treated with Andro (50MUM) for the indicated time. Functional annotation of the target genes based on the differentially expressed miRNAs demonstrated that the majority of the genes were involved in a variety of signaling pathways, including miRNAs in cancer, mitogen activated protein kinases (MPAKs), focal adhesion. Furthermore, the expression of 24 target genes (total 31) involved in above signaling pathways based on miRNAs analysis was found to be consistent with the alteration of miRNAs. CONCLUSIONS: The results demonstrate that Andro alters the expression of miRNAs profile and downstream signals, which may contribute to its inhibition on hepatoma tumor growth. PMID- 27182053 TI - Transcriptome characterization and gene expression analysis related to sexual dimorphism in the ghost moth, Thitarodes pui, a host of Ophiocordyceps sinensis. AB - Thitarodes pui is one of the host species of the Chinese caterpillar fungus Ophiocordyceps sinensis as a traditional Chinese medicine with economic and medical importance. The pupal and adult stages of T. pui are sexually dimorphic. In order to elucidate the molecular mechanisms involved in the sexually dimorphic development of T. pui, we compared the transcriptomes of female and male pupae and adults. We obtained 15,881,734, 16,962,086, 17,514,743, and 17,770,904 clean reads from female pupae, male pupae, female adults, and male adults, respectively. The reads obtained from the four samples were pooled and assembled into 65,165 unigenes, 23,597 of which were annotated. Candidate genes involved in sexual development were identified and analysed. Gene expression analysis revealed that 1406 genes were differentially expressed in male and female pupae, 448 of which were up-regulated in males and 958 were up-regulated in females. A total of 2025 genes were differentially expressed in male and females adults, 1304 of which were up-regulated in males and 721 were up-regulated in females. The functional enrichment of the differentially expressed genes indicated that reproduction and cuticle synthesis were regulated differently between the sexes. The transcriptome data obtained provide significant information regarding the genes involved in sexually dimorphic development, which will improve our understanding of the molecular mechanisms related to sexual dimorphism and helpful for the moth mass rearing which would provide enough host insects for the sustainable utilization of O. sinensis. PMID- 27182054 TI - Nuclear magnetic resonance in Kondo lattice systems. AB - Nuclear magnetic resonance has emerged as a vital tool to explore the fundamental physics of Kondo lattice systems. Because nuclear spins experience two different hyperfine couplings to the itinerant conduction electrons and to the local f moments, the Knight shift can probe multiple types of spin correlations that are not accessible via other techniques. The Knight shift provides direct information about the onset of heavy electron coherence and the emergence of the heavy electron fluid. PMID- 27182052 TI - Endocrine disrupting chemical, bisphenol-A, induces breast cancer associated gene HOXB9 expression in vitro and in vivo. AB - HOXB9 is a homeobox-containing gene that plays a key role in mammary gland development and is associated with breast and other types of cancer. Here, we demonstrate that HOXB9 expression is transcriptionally regulated by estradiol (E2), in vitro and in vivo. We also demonstrate that the endocrine disrupting chemical bisphenol-A (BPA) induces HOXB9 expression in cultured human breast cancer cells (MCF7) as well as in vivo in the mammary glands of ovariectomized (OVX) rats. Luciferase assay showed that estrogen-response-elements (EREs) in the HOXB9 promoter are required for BPA-induced expression. Estrogen-receptors (ERs) and ER-co-regulators such as MLL-histone methylase (MLL3), histone acetylases, CBP/P300, bind to the HOXB9 promoter EREs in the presence of BPA, modify chromatin (histone methylation and acetylation) and lead to gene activation. In summary, our results demonstrate that BPA exposure, like estradiol, increases HOXB9 expression in breast cells both in vitro and in vivo through a mechanism that involves increased recruitment of transcription and chromatin modification factors. PMID- 27182055 TI - Understanding disease processes by partitioned dynamic Bayesian networks. AB - For many clinical problems in patients the underlying pathophysiological process changes in the course of time as a result of medical interventions. In model building for such problems, the typical scarcity of data in a clinical setting has been often compensated by utilizing time homogeneous models, such as dynamic Bayesian networks. As a consequence, the specificities of the underlying process are lost in the obtained models. In the current work, we propose the new concept of partitioned dynamic Bayesian networks to capture distribution regime changes, i.e. time non-homogeneity, benefiting from an intuitive and compact representation with the solid theoretical foundation of Bayesian network models. In order to balance specificity and simplicity in real-world scenarios, we propose a heuristic algorithm to search and learn these non-homogeneous models taking into account a preference for less complex models. An extensive set of experiments were ran, in which simulating experiments show that the heuristic algorithm was capable of constructing well-suited solutions, in terms of goodness of fit and statistical distance to the original distributions, in consonance with the underlying processes that generated data, whether it was homogeneous or non homogeneous. Finally, a study case on psychotic depression was conducted using non-homogeneous models learned by the heuristic, leading to insightful answers for clinically relevant questions concerning the dynamics of this mental disorder. PMID- 27182057 TI - Letter to the Editor: The effect of autonomic nervous system on the impairment of glucose uptake and lipid metabolism in epicardial adipose tissue. PMID- 27182056 TI - T cell immunoglobulin and mucin domain-containing molecule 3 on CD14+ monocytes serves as a novel biological marker for diabetes duration in type 2 diabetes mellitus. AB - AIMS/INTRODUCTION: Type 2 diabetes is a worldwide disease that is associated with increased rates of obesity and reduced physical activity. Obesity-associated insulin resistance in type 2 diabetes is a disorder in the balance between pro inflammatory and anti-inflammatory signals. T cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) has been reported as an important regulatory inflammation molecule, and plays a pivotal role in several inflammation-related diseases. MATERIALS AND METHODS: Peripheral blood mononuclear cells were obtained from type 2 diabetes patients (n = 31) and healthy donors (n = 18), and Tim-3 expression on peripheral blood mononuclear cells was evaluated by flow cytometry. RESULTS: We showed the downregulated expression of Tim-3 on CD14+ monocytes from type 2 diabetes patients. In addition, the upregulated expression of Tim-3 on peripheral CD4+ T cells and CD8+ T cells was observed in the present study. The correlation analysis between Tim-3 expression on CD14+ monocytes and diabetes duration showed the longer diabetes duration time, the lower Tim-3 expression on CD14 monocytes. CONCLUSIONS: The present results suggest that Tim-3 might participate in the progression of type 2 diabetes by its negative regulation on these immune cells, and Tim-3 on CD14+ monocytes serves as a novel biological marker for diabetes duration in type 2 diabetes patients. PMID- 27182058 TI - Reply to Katlandur, Ozbek, and Keser. PMID- 27182059 TI - Corrigendum. PMID- 27182062 TI - Upon Wnt stimulation, Rac1 activation requires Rac1 and Vav2 binding to p120 catenin. PMID- 27182061 TI - Expanding functions of GIT Arf GTPase-activating proteins, PIX Rho guanine nucleotide exchange factors and GIT-PIX complexes. AB - The GIT proteins, GIT1 and GIT2, are GTPase-activating proteins (inactivators) for the ADP-ribosylation factor (Arf) small GTP-binding proteins, and function to limit the activity of Arf proteins. The PIX proteins, alpha-PIX and beta-PIX (also known as ARHGEF6 and ARHGEF7, respectively), are guanine nucleotide exchange factors (activators) for the Rho family small GTP-binding protein family members Rac1 and Cdc42. Through their multi-domain structures, GIT and PIX proteins can also function as signaling scaffolds by binding to numerous protein partners. Importantly, the constitutive association of GIT and PIX proteins into oligomeric GIT-PIX complexes allows these two proteins to function together as subunits of a larger structure that coordinates two distinct small GTP-binding protein pathways and serves as multivalent scaffold for the partners of both constituent subunits. Studies have revealed the involvement of GIT and PIX proteins, and of the GIT-PIX complex, in numerous fundamental cellular processes through a wide variety of mechanisms, pathways and signaling partners. In this Commentary, we discuss recent findings in key physiological systems that exemplify current understanding of the function of this important regulatory complex. Further, we draw attention to gaps in crucial information that remain to be filled to allow a better understanding of the many roles of the GIT-PIX complex in health and disease. PMID- 27182060 TI - Nuclear migration events throughout development. AB - Moving the nucleus to a specific position within the cell is an important event during many cell and developmental processes. Several different molecular mechanisms exist to position nuclei in various cell types. In this Commentary, we review the recent progress made in elucidating mechanisms of nuclear migration in a variety of important developmental models. Genetic approaches to identify mutations that disrupt nuclear migration in yeast, filamentous fungi, Caenorhabditis elegans, Drosophila melanogaster and plants led to the identification of microtubule motors, as well as Sad1p, UNC-84 (SUN) domain and Klarsicht, ANC-1, Syne homology (KASH) domain proteins (LINC complex) that function to connect nuclei to the cytoskeleton. We focus on how these proteins and various mechanisms move nuclei during vertebrate development, including processes related to wound healing of fibroblasts, fertilization, developing myotubes and the developing central nervous system. We also describe how nuclear migration is involved in cells that migrate through constricted spaces. On the basis of these findings, it is becoming increasingly clear that defects in nuclear positioning are associated with human diseases, syndromes and disorders. PMID- 27182063 TI - Tocilizumab in Giant Cell Arteritis: A Multicenter Retrospective Study of 34 Patients. AB - OBJECTIVE: To report the efficacy and safety of tocilizumab (TCZ) for giant cell arteritis (GCA). METHODS: A retrospective multicenter study that included 34 patients receiving TCZ for GCA. RESULTS: TCZ was effective in all but 6 patients, who still had mild symptoms. Mean glucocorticoid dose was tapered. One patient died and 3 patients had to stop TCZ therapy because of severe adverse events. Twenty-three patients stopped treatment; 8 of these experienced relapses after a mean of 3.5 +/- 1.3 months. CONCLUSION: TCZ is effective in GCA. However, side effects occur. Whether this treatment has only a suspensive effect remains to be determined. PMID- 27182064 TI - The Association Between Serum 25-hydroxy Vitamin D Level and Upper Leg Strength in Patients with Knee Osteoarthritis: Results of the Amsterdam Osteoarthritis Cohort. AB - OBJECTIVE: Vitamin D deficiency, which is common among elderly people, has been linked to muscle weakness. In patients with knee osteoarthritis (OA), the association between muscle strength and serum 25-hydroxy Vitamin D [25(OH)D] level has not been studied comprehensively. The aim of our study was to examine the association between serum 25(OH)D level and muscle strength in patients with knee OA. METHODS: Data of the Amsterdam Osteoarthritis cohort from 319 participants with knee OA were used in a cross-sectional study. Serum 25(OH)D level (nmol/l) was measured by a competitive electrochemiluminescence method. Muscle strength (nm/kg) of the upper leg was measured isokinetically. Univariable and multivariable linear regression analyses were used to calculate the association between serum 25(OH)D level and muscle strength. RESULTS: Serum 25(OH)D level was significantly associated with muscle strength (B = 0.036, 95% CI 0.017-0.054, p < 0.001), adjusted for season of blood collection. After adding body mass index (BMI) to the model, this association was no longer significant (B = 0.011, 95% CI -0.007 to 0.029, p = 0.214). Alcohol consumption, number of comorbidities, and sex were subsequently added and changed the model slightly. Without BMI, this model showed a significant association between serum 25(OH)D level and muscle strength (B = 0.029, 95% CI 0.014-0.043, p < 0.001). CONCLUSION: The observed association between a low serum 25(OH)D level and muscle weakness in patients with knee OA is attenuated by BMI. Further studies are needed to explain the associations among Vitamin D level, muscle strength, and adiposity in patients with knee OA. PMID- 27182065 TI - Exploring Fatigue Trajectories in Early Symptomatic Knee and Hip Osteoarthritis: 6-year Results from the CHECK Study. AB - OBJECTIVE: To examine whether different groups of fatigue trajectories can be identified among patients with early symptomatic osteoarthritis (OA) of the knee or hip, to describe the level of fatigue severity within each of these fatigue groups, and to investigate the involvement of age, sex, use of medication, comorbidity, and OA severity in relation to group membership. METHODS: Six years of followup data on fatigue (Medical Outcomes Study Short Form-36 Vitality scale) came from the Cohort Hip and Cohort Knee (CHECK) cohort. Growth mixture modeling was applied to identify distinct fatigue trajectories as well as to take into account the effects of the patient characteristics. RESULTS: Three fatigue trajectories were identified: low fatigue, low-to-high fatigue, and high fatigue. Latter trajectories showed considerable overlap from years 2 to 6, but differed in some patient characteristics in comparison with each other and in comparison with the low fatigue group. Comorbidity, medication use, and sex were significantly associated with the identified trajectories. Women, individuals with a comorbid disease, and those who used medication were more likely to follow a high fatigue trajectory. CONCLUSION: These findings suggest heterogeneous development of fatigue in the early OA population associated with varying patient characteristics. Further, this study shows that a considerable number of patients with OA already experience elevated levels of fatigue at an early stage of OA. While these findings need to be replicated, the identification of these trajectories with differing patient characteristics may warrant tailored psychosocial interventions for patients with elevated levels of fatigue. PMID- 27182066 TI - Differential Expression Profiles of Long Noncoding RNA and mRNA of Osteogenically Differentiated Mesenchymal Stem Cells in Ankylosing Spondylitis. AB - OBJECTIVE: We previously demonstrated that mesenchymal stem cells (MSC) from patients with ankylosing spondylitis (AS; ASMSC) have a greater osteogenic differentiation capacity than MSC from healthy donors (HDMSC) and that this difference underlies the pathogenesis of pathological osteogenesis in AS. Here we compared expression levels of long noncoding RNA (lncRNA) and mRNA between osteogenically differentiated ASMSC and HDMSC and explored the precise mechanism underlying abnormal osteogenic differentiation in ASMSC. METHODS: HDMSC and ASMSC were induced with osteogenic differentiation medium for 10 days. Microarray analyses were then performed to identify lncRNA and mRNA differentially expressed between HDMSC and ASMSC, which were then subjected to bioinformatics analysis and confirmed by quantitative real-time PCR (qRT-PCR) assays. In addition, coding-non coding gene co-expression (CNC) networks were constructed to examine the relationships between the lncRNA and mRNA expression patterns. RESULTS: A total of 520 lncRNA and 665 mRNA were differentially expressed in osteogenically differentiated ASMSC compared with HDMSC. Bioinformatics analysis revealed 64 signaling pathways with significant differences, including transforming growth factor-beta signaling. qRT-PCR assays confirmed the reliability of the microarray data. The CNC network indicated that 4 differentially expressed lncRNA, including lnc-ZNF354A-1, lnc-LIN54-1, lnc-FRG2C-3, and lnc-USP50-2 may be involved in the abnormal osteogenic differentiation of ASMSC. CONCLUSION: Our study characterized the differential lncRNA and mRNA expression profiles of osteogenically differentiated ASMSC and identified 4 lncRNA that may participate in the abnormal osteogenic differentiation of ASMSC. These results provide insight into the pathogenesis of pathological osteogenesis in AS. PMID- 27182067 TI - Development and Validation of a Short Form of the Social Role Participation Questionnaire in Patients with Ankylosing Spondylitis. AB - OBJECTIVE: The Social Role Participation Questionnaire (SRPQ) assesses the influence of health on 11 specific roles and 1 general role along 4 dimensions. In this study, a shortened version of the SRPQ (s-SRPQ) was developed in patients with ankylosing spondylitis (AS) to facilitate data collection in clinical studies and practice. METHODS: Using data from 246 patients with AS and population controls, the fit of each role to the different participation dimensions, the contribution of each role to the measurement precision, and the correlation between dimensions were evaluated using item response theory. Representation of the 3 participation chapters of the International Classification of Functioning, Disability, and Health was ensured. Reliability of each dimension of both versions of the SRPQ was compared by correlating scores to the Medical Outcomes Study Short Form-36 (SF-36) and the Satisfaction With Life Scale (SWLS), and by comparing ability to discriminate between patients and controls and between patients with low and high disease activity (Bath Ankylosing Spondylitis Disease Activity Index >= 4). RESULTS: The s-SRPQ, which assesses participation across 6 social roles along 2 dimensions (physical difficulty and satisfaction with performance), was proposed. Both dimensions of the s-SRPQ were highly reliable (r >= 0.86) and were shown to have construct validity as indicated by a similar pattern of correlations with the SF-36 and SWLS as the original SRPQ dimensions. Both versions discriminated well between patients and controls and between patients with high versus low disease activity (relative validity >= 0.72). CONCLUSION: The s-SRPQ retains the measurement properties of the original SRPQ and seems useful for measuring the effect of AS on participation. PMID- 27182068 TI - The Efficacy of a Dance Intervention as Cognitive Training for the Old-Old. AB - This research investigates the efficacy of a dance intervention of moderate length (10 weeks, 45 min/week) on a sample of old-old adults living in a residential care setting. The study focused on the effect of the intervention on aspects of cognitive functioning (short-term memory, executive functioning). In addition, changes in general self-efficacy and life satisfaction were investigated. Twenty-four older adults (mean age M = 80.8), with no cognitive impairments, participated in the study. Participants were randomly assigned to two programs: the experimental group attended the dance intervention, while the active control group was involved in an alternative (nondance) program. A pretest, posttest, and follow-up measurement was conducted. A 2 * 3 mixed design ANOVA revealed benefits in short-term memory and executive functioning for the trained group, but not for the active control, and this benefit was maintained at the 5 months follow-up. These results suggest that training procedures, based on dance, could improve cognitive functioning in the old-old. PMID- 27182069 TI - Penalized or Protected? Gender and the Consequences of Nonstandard and Mismatched Employment Histories. AB - Millions of workers are employed in positions that deviate from the full-time, standard employment relationship or work in jobs that are mismatched with their skills, education, or experience. Yet, little is known about how employers evaluate workers who have experienced these employment arrangements, limiting our knowledge about how part-time work, temporary agency employment, and skills underutilization affect workers' labor market opportunities. Drawing on original field and survey experiment data, I examine three questions: (1) What are the consequences of having a nonstandard or mismatched employment history for workers' labor market opportunities? (2) Are the effects of nonstandard or mismatched employment histories different for men and women? and (3) What are the mechanisms linking nonstandard or mismatched employment histories to labor market outcomes? The field experiment shows that skills underutilization is as scarring for workers as a year of unemployment, but that there are limited penalties for workers with histories of temporary agency employment. Additionally, although men are penalized for part-time employment histories, women face no penalty for part time work. The survey experiment reveals that employers' perceptions of workers' competence and commitment mediate these effects. These findings shed light on the consequences of changing employment relations for the distribution of labor market opportunities in the "new economy." PMID- 27182070 TI - Biodiversity, ecosystem functioning, and classical biological control. AB - Increasing concern over worldwide loss of biodiversity has led ecologists to focus intently on how ecosystem functioning may depend on diversity. In applied entomology, there is longstanding interest in the issue, especially as regards the importance of natural enemy diversity for pest control. Here I review parallels in interest, conceptual framework, and conclusions concerning biodiversity as it affects ecosystem functioning in general and classical biological control in particular. Whereas the former focuses on implications of loss of diversity, the latter focuses on implications of increase in diversity as additional species of natural enemies are introduced to novel communities in new geographic regions for insect pest and weed control. Many field studies now demonstrate that ecosystem functioning, e.g., as reflected in primary productivity, is enhanced and stabilized over time by high diversity as the community increases in its efficiency in exploiting available resources. Similarly, there is growing field support for the generalization that increasing species and functional diversity of natural enemies leads to increasing pest suppression. Nonetheless a central concern of classical biological control in particular, as it seeks to minimize non-target effects, remains as to whether one or a few species of natural enemies can provide sufficient pest control. PMID- 27182071 TI - An Aegilops ventricosa Translocation Confers Resistance Against Root-knot Nematodes to Common Wheat. AB - Root knot nematodes (RKN; Meloidogyne spp.) cause severe losses worldwide to a wide range of crops. Crop rotations with resistant hosts can be used to control losses, but the wide host range of RKN limits this option. In this study, we found that the wheat cultivar Lassik is resistant to several isolates of the RKN species M. incognita and M. javanica, including those that can reproduce on tomato with the resistance gene Mi-1. Comparison of near-isogenic lines of wheat showed that the wheat resistance gene(s) is localized within a segment of the short arm of chromosome 2N from Aegilops ventricosa (Zhuk.) Chennav translocated into common wheat (Triticum aestivum L.) chromosome arm 2AS and is associated with a highly significant decrease in RKN eggs in the roots. This RKN resistance gene has been assigned the name Rkn3. While wheat itself is tolerant of RKN infection, a microplot experiment coupled with tomato bioassays showed less RKN root galling in the tomato samples grown in soil from the previous microplots including RKN resistant wheat varieties than in those including a susceptible wheat isogenic line. This result suggests that rotation with Rkn3 resistant wheat cultivars has the potential to be a valuable component of nematode management for crops that are highly susceptible to nematode damage and for which alternative strategies are limited. PMID- 27182072 TI - The 'empty choice': A sociological examination of choosing medical research participation in resource-limited Sub-Saharan Africa. AB - This article explores the views of frontline research staff in different Sub Saharan African contexts on the notion of choice in biomedical research. It argues that the current emphasis on individual choice, in the conduct of biomedical research, ignores significant structural and contextual factors in resource-limited settings. These factors severely constrain individual options and often make biomedical research enrolment the most amenable route to healthcare for the world's poorest. From the position of frontline research staff, local contextual factors and structural issues narrowly frame the parameters within which many prospective participants are asked to choose, to such an extent that individuals are effectively presented with an 'empty choice'. The article draws on ethnographic and interview data and insights gained through graphic elucidation techniques. It demonstrates that for frontline research staff, macro-level structural factors and their bearing on everyday realities shape what choice in biomedical research participation means in practice. PMID- 27182073 TI - Maize Germplasm Conservation in Southern California's Urban Gardens: Introduced Diversity Beyond ex situ and in situ Management. AB - Contemporary germplasm conservation studies largely focus on ex situ and in situ management of diversity within centers of genetic diversity. Transnational migrants who transport and introduce landraces to new locations may catalyze a third type of conservation that combines both approaches. Resulting populations may support reduced diversity as a result of evolutionary forces such as genetic drift, selection, and gene flow, yet they may also be more diverse as a result of multiple introductions, selective breeding and cross pollination among multiple introduced varietals. In this study, we measured the amount and structure of maize molecular genetic diversity in samples collected from home gardens and community gardens maintained by immigrant farmers in Southern California. We used the same markers to measure the genetic diversity and structure of commercially available maize varieties and compared our data to previously reported genetic diversity statistics of Mesoamerican landraces. Our results reveal that transnational dispersal creates an opportunity for the maintenance of maize genetic diversity beyond its recognized centers of diversity. PMID- 27182074 TI - Improving the Factor Structure of Psychological Scales: The Expanded Format as an Alternative to the Likert Scale Format. AB - Many psychological scales written in the Likert format include reverse worded (RW) items in order to control acquiescence bias. However, studies have shown that RW items often contaminate the factor structure of the scale by creating one or more method factors. The present study examines an alternative scale format, called the Expanded format, which replaces each response option in the Likert scale with a full sentence. We hypothesized that this format would result in a cleaner factor structure as compared with the Likert format. We tested this hypothesis on three popular psychological scales: the Rosenberg Self-Esteem scale, the Conscientiousness subscale of the Big Five Inventory, and the Beck Depression Inventory II. Scales in both formats showed comparable reliabilities. However, scales in the Expanded format had better (i.e., lower and more theoretically defensible) dimensionalities than scales in the Likert format, as assessed by both exploratory factor analyses and confirmatory factor analyses. We encourage further study and wider use of the Expanded format, particularly when a scale's dimensionality is of theoretical interest. PMID- 27182075 TI - Defining Tiger Parenting in Chinese Americans. AB - "Tiger" parenting, as described by Amy Chua [2011], has instigated scholarly discourse on this phenomenon and its possible effects on families. Our eight-year longitudinal study, published in the Asian American Journal of Psychology [Kim, Wang, Orozco-Lapray, Shen, & Murtuza, 2013b], demonstrates that tiger parenting is not a common parenting profile in a sample of 444 Chinese American families. Tiger parenting also does not relate to superior academic performance in children. In fact, the best developmental outcomes were found among children of supportive parents. We examine the complexities around defining tiger parenting by reviewing classical literature on parenting styles and scholarship on Asian American parenting, along with Amy Chua's own description of her parenting method, to develop, define, and categorize variability in parenting in a sample of Chinese American families. We also provide evidence that supportive parenting is important for the optimal development of Chinese American adolescents. PMID- 27182076 TI - The Social Practice of Harm Reduction in Argentina: A "Latin" Kind of Intervention. AB - "Harm reduction" is a public health model that places emphasis on reducing the negative effects of drug use rather than on eliminating drug use or ensuring abstinence. Based on sixteen months of ethnographic research, this article examines how harm reduction in Argentina is both envisioned and observed as a social practice by analyzing how local harm reductionists position their work in relation to "social context." My informants consider this social emphasis to be characteristic of a "Latin" kind of intervention, which they differentiate from an "Anglo-Saxon" approach focused on individual behavior change. Differentiating between these "cultural" models of intervention helps Argentine harm reductionists guide their social orientation to drug use, risk, and harm by situating interventions in the contexts in which users live and operate. It also allows them to distinguish their social form of harm reduction from a neoliberal one that they associate with the global north. The construction of these distinct cultural models of intervention is a means of critiquing neoliberal approaches to health that advocate technical solutions to changing individual behavior. Ultimately, this construct acts as a political commentary on the limits of an individual-oriented harm reduction project when applied to the "Argentine context." PMID- 27182077 TI - Characterization of Large-Area SiPM Array for PET Applications. AB - The performance of an 8 * 8 array of 6.0 * 6.0 mm2 (active area) SiPMs was evaluated for PET applications using crystal arrays with different pitch sizes (3.4 mm, 1.5 mm, 1.35 mm and 1.2 mm) and custom designed five-channel front-end readout electronics (four channels for position information and one channel for timing information). The total area of this SiPM array is 57.4 * 57.4 mm2, and the pitch size is 7.2 mm. It was fabricated using enhanced blue sensitivity SiPMs (MicroFB-60035-SMT) with peak spectral sensitivity at 420 nm. The performance of the SiPM array was characterized by measuring flood histogram decoding quality, energy resolution, timing resolution and saturation at several bias voltages (from 25.0 V to 30.0 V in 0.5 V intervals) and two different temperatures (5 degrees C and 20 degrees C). Results show that the best flood histogram was obtained at a bias voltage of 28.0 V and 5 degrees C and an array of polished LSO crystals with a pitch as small as 1.2 mm can be resolved. No saturation was observed up to a bias voltage of 29.5 V during the experiments, due to adequate light sharing between SiPMs. Energy resolution and timing resolution at 5 degrees C ranged from 12.7 +/- 0.8% to 14.6 +/- 1.4 % and 1.58 +/- 0.13 ns to 2.50 +/- 0.44 ns, for crystal array pitch sizes of 3.4 mm and 1.2 mm respectively. Superior flood histogram quality, energy resolution and timing resolution were obtained with larger crystal array pitch sizes and at lower temperature. Based on our findings, we conclude that this large-area SiPM array can serve as a suitable photodetector for high-resolution small-animal PET or dedicated human brain PET scanners. PMID- 27182078 TI - Design of a Multi-Pinhole Collimator for I-123 DaTscan Imaging on Dual-Headed SPECT Systems in Combination with a Fan-Beam Collimator. AB - For the 2011 FDA approved Parkinson's Disease (PD) SPECT imaging agent I-123 labeled DaTscan, the volume of interest (VOI) is the interior portion of the brain. However imaging of the occipital lobe is also required with PD for calculation of the striatal binding ratio (SBR), a parameter of significance in early diagnosis, differentiation of PD from other disorders with similar clinical presentations, and monitoring progression. Thus we propose the usage of a combination of a multi-pinhole (MPH) collimator on one head of the SPECT system and a fan-beam on the other. The MPH would be designed to provide high resolution and sensitivity for imaging of the interior portion of the brain. The fan-beam collimator would provide lower resolution but complete sampling of the brain addressing data sufficiency and allowing a volume-of-interest to be defined over the occipital lobe for calculation of SBR's. Herein we focus on the design of the MPH component of the combined system. Combined reconstruction will be addressed in a subsequent publication. An analysis of 46 clinical DaTscan studies was performed to provide information to define the VOI, and design of a MPH collimator to image this VOI. The system spatial resolution for the MPH was set to 4.7 mm, which is comparable to that of clinical PET systems, and significantly smaller than that of fan-beam collimators employed in SPECT. With this set, we compared system sensitivities for three aperture array designs, and selected the 3 * 3 array due to it being the highest of the three. The combined sensitivity of the apertures for it was similar to that of an ultra-high resolution fan-beam (LEUHRF) collimator, but smaller than that of a high-resolution fan-beam collimator (LEHRF). On the basis of these results we propose the further exploration of this design through simulations, and the development of combined MPH and fan-beam reconstruction. PMID- 27182079 TI - Modeling the respiratory motion of solitary pulmonary nodules and determining the impact of respiratory motion on their detection in SPECT imaging. AB - The objectives of this investigation were to model the respiratory motion of solitary pulmonary nodules (SPN) and then use this model to determine the impact of respiratory motion on the localization and detection of small SPN in SPECT imaging for four reconstruction strategies. The respiratory motion of SPN was based on that of normal anatomic structures in the lungs determined from breath held CT images of a volunteer acquired at two different stages of respiration. End-expiration (EE) and time-averaged (Frame Av) non-uniform-B-spline cardiac torso (NCAT) digital-anthropomorphic phantoms were created using this information for respiratory motion within the lungs. SPN were represented as 1 cm diameter spheres which underwent linear motion during respiration between the EE and end inspiration (EI) time points. The SIMIND Monte Carlo program was used to produce SPECT projection data simulating Tc-99m depreotide (NeoTect) imaging. The projections were reconstructed using 1) no correction (NC), 2) attenuation correction (AC), 3) resolution compensation (RC), and 4) attenuation correction, scatter correction, and resolution compensation (AC_SC_RC). A human-observer localization receiver operating characteristics (LROC) study was then performed to determine the difference in localization and detection accuracy with and without the presence of respiratory motion. The LROC comparison determined that respiratory motion degrades tumor detection for all four reconstruction strategies, thus correction for SPN motion would be expected to improve detection accuracy. The inclusion of RC in reconstruction improved detection accuracy for both EE and Frame Av over NC and AC. Also the magnitude of the impact of motion was least for AC_SC_RC. PMID- 27182081 TI - Stability of the Baseline Holder in Readout Circuits For Radiation Detectors. AB - Baseline holder (BLH) circuits are used widely to stabilize the analog output of application-specific integrated circuits (ASICs) for high-count-rate applications. The careful design of BLH circuits is vital to the overall stability of the analog-signal-processing chain in ASICs. Recently, we observed self-triggered fluctuations in an ASIC in which the shaping circuits have a BLH circuit in the feedback loop. In fact, further investigations showed that methods of enhancing small-signal stabilities cause an even worse situation. To resolve this problem, we used large-signal analyses to study the circuit's stability. We found that a relatively small gain for the error amplifier and a small current in the non-linear stage of the BLH are required to enhance stability in large-signal analysis, which will compromise the properties of the BLH. These findings were verified by SPICE simulations. In this paper, we present our detailed analysis of the BLH circuits, and propose an improved version of them that have only minimal self-triggered fluctuations. We summarize the design considerations both for the stability and the properties of the BLH circuits. PMID- 27182080 TI - LROC Investigation of Three Strategies for Reducing the Impact of Respiratory Motion on the Detection of Solitary Pulmonary Nodules in SPECT. AB - The objective of this investigation was to determine the effectiveness of three motion reducing strategies in diminishing the degrading impact of respiratory motion on the detection of small solitary pulmonary nodules (SPN) in single photon emission computed tomographic (SPECT) imaging in comparison to a standard clinical acquisition and the ideal case of imaging in the absence of respiratory motion. To do this non-uniform rational B-spline cardiac-torso (NCAT) phantoms based on human-volunteer CT studies were generated spanning the respiratory cycle for a normal background distribution of Tc-99m NeoTect. Similarly, spherical phantoms of 1.0 cm diameter were generated to model small SPN for each of 150 uniquely located sites within the lungs whose respiratory motion was based on the motion of normal structures in the volunteer CT studies. The SIMIND Monte Carlo program was used to produce SPECT projection data from these. Normal and single lesion containing SPECT projection sets with a clinically realistic Poisson noise level were created for the cases of: 1) the end-expiration (EE) frame with all counts, 2) respiration-averaged motion with all counts, 3) one-fourth of the 32 frames centered around EE (Quarter-Binning), 4) one-half of the 32 frames centered around EE (Half-Binning), and 5) eight temporally binned frames spanning the respiratory cycle. Each of the sets of combined projection data were reconstructed with RBI-EM with system spatial-resolution compensation (RC). Based on the known motion for each of the 150 different lesions, the reconstructed volumes of respiratory bins were shifted so as to superimpose the locations of the SPN onto that in the first bin (Reconstruct and Shift). Five human-observers performed localization receiver operating characteristics (LROC) studies of SPN detection. The observer results were analyzed for statistical significance differences in SPN detection accuracy among the three correction strategies, the standard acquisition, and the ideal case of the absence of respiratory motion. Our human-observer LROC determined that Quarter-Binning and Half-Binning strategies resulted in SPN detection accuracy statistically significantly below (P < 0.05) that of standard clinical acquisition, whereas the Reconstruct and Shift strategy resulted in a detection accuracy not statistically significantly different from that of the ideal case. This investigation demonstrates that tumor detection based on acquisitions associated with less than all the counts which could potentially be employed may result in poorer detection despite limiting the motion of the lesion. The Reconstruct and Shift method results in tumor detection that is equivalent to ideal motion correction. PMID- 27182082 TI - Probing surface recombination velocities in semiconductors using two-photon microscopy. AB - The determination of minority-carrier lifetimes and surface recombination velocities is essential for the development of semiconductor technologies such as solar cells. The recent development of two-photon time-resolved microscopy allows for better measurements of bulk and subsurface interfaces properties. Here we analyze the diffusion problem related to this optical technique. Our three dimensional treatment enables us to separate lifetime (recombination) from transport effects (diffusion) in the photoluminescence intensity. It also allows us to consider surface recombination occurring at a variety of geometries: a single plane (representing an isolated exposed or buried interface), two parallel planes (representing two inequivalent interfaces), and a spherical surface (representing the enclosing surface of a grain boundary). We provide fully analytical results and scalings directly amenable to data fitting, and apply those to experimental data collected on heteroepitaxial CdTe/ZnTe/Si. PMID- 27182083 TI - Nurse going native: Language and identity in letters from Africa and the British West Indies. AB - Colonial nurses were ideal agents of colonial medicine's supposed beneficence: while practising and teaching "hygiene", they also reinforced racial and cultural separation. In some cases, however, the nurses took their role as healers and teachers of local populations much more seriously than was authorized implicitly by their employer. This article analyses the circulation of original life writing materials between one nurse, CC, and the Colonial Nursing Association, in order to chart the considerable anxiety around the concept of nurses' cross-cultural and cross-racial sympathy during the interwar period. I draw upon colonial language studies and women's travel writing analysis in order to demonstrate that many of these concerns centred on issues of language and communication. By speaking local languages, it was feared that colonial nurses' loyalty would shift from their employer towards their indigenous patients. This essay places the concept of "going native" within the contexts of nineteenth-century empire literature, racial anthropology and ethnology, in order to suggest that concerns about nurses "going native" were influenced by discourses of degeneration and acclimatization. PMID- 27182084 TI - The Analysis of Duocentric Social Networks: A Primer. AB - Marriages and other intimate partnerships are facilitated or constrained by the social networks within which they are embedded. To date, methods used to assess the social networks of couples have been limited to global ratings of social network characteristics or network data collected from each partner separately. In the current article, the authors offer new tools for expanding on the existing literature by describing methods of collecting and analyzing duocentric social networks, that is, the combined social networks of couples. They provide an overview of the key considerations for measuring duocentric networks, such as how and why to combine separate network interviews with partners into one shared duocentric network, the number of network members to assess, and the implications of different network operationalizations. They illustrate these considerations with analyses of social network data collected from 57 low-income married couples, presenting visualizations and quantitative measures of network composition and structure. PMID- 27182085 TI - Poly(thioester) by Organocatalytic Ring-Opening Polymerization. AB - Organocatalysts typically used for the ring-opening polymerization (ROP) of cyclic ester monomers are applied to a thiolactone, epsilon-thiocaprolactone (tCL). In the absence of an H-bond donor, a nucleophilic polymerization mechanism is proposed. Despite the decreased ability of thioesters and thiols (versus esters and alcohols) to H-bond, H-bonding organocatalysts-a thiourea in combination with an H-bond accepting base-are also effective for the ROP of tCL. The increased nucleophilicity of thiols (versus alcohols) is implicated in the increased Mw/Mn of the poly(thiocaprolactone) versus poly(caprolactone), but deleterious transesterification is suppressed in the presence of a thiourea. The thioester monomer, tCL, is shown to be thermodynamically similar to epsilon caprolactam but kinetically similar to epsilon-caprolactone. PMID- 27182086 TI - Rate Accelerated Organocatalytic Ring-Opening Polymerization of L-Lactide via the Application of a Bis(thiourea) H-bond Donating Cocatalyst. AB - A cocatalyst system consisting of an alkylamine base and a bis(thiourea) featuring a linear alkane tether is shown to dramatically increase the rate of ring-opening polymerization (ROP) of L-lactide versus previously disclosed monothiourea H-bond donors. Rate acceleration occurs regardless of the identity of the alkylamine cocatalyst, and the ROP remains controlled yielding poly(lactide) with narrow molecular weight distributions, predictable molecular weights and high selectivity for monomer. This H-bond mediated ROP of L-lactide constitutes a rare, clear example of rate acceleration with bis(thiourea) H-bond donors versus monothioureas, and the bis(thiourea) is shown to remain highly active for ROP at fractional percent catalyst loadings. Activation at a single monomer ester by both thiourea moieties is implicated as the source of rate acceleration. PMID- 27182087 TI - Controlled Organocatalytic Ring-Opening Polymerization of epsilon Thionocaprolactone. AB - For the first time, the controlled ring-opening polymerization (ROP) of epsilon thionocaprolactone (tnCL) is conducted. The organocatalytic ROP of tnCL occurs without carbonyl scrambling, leading to homopoly(epsilon-thionocaprolactone) (PtnCL). The ROP by base catalysts alone is proposed to proceed via a nucleophilic mechanism, while the addition of an H-bond donating thiourea (TU) is shown to provide excellent reaction control. The increased reaction control provided by the TU occurs in the virtual absence of binding between tnCL and TU, and a mechanistic account for this observation is discussed. The monomer ring strain is measured and found to be similar to delta-valerolactone (VL). Copolymers with VL are synthesized, and the resulting analysis of the copolymer materials properties provides the only known physical characterizations of poly(thio(no)ester-co-ester)s. PMID- 27182088 TI - Contingency Enhances Sensitivity to Loss in a Gambling Task with Diminishing Returns. AB - This study examined whether gambling behavior under conditions of diminishing returns differed between participants with histories of contingent (CD group) and noncontingent (NCD group) token delivery. In Phase 1, CD participants accrued tokens by correctly completing a discrimination task; for NCD participants, token accrual was yoked to token delivery of CD participants. In Phase 2, participants could choose to gamble their tokens or end the experiment and exchange their tokens for money. During the gambling task, participants could bet one token per trial. The probability of losses began at 10% and increased incrementally across blocks of 10 trials up to 100%. Overall, participants in the CD group gambled on fewer trials than participants in the NCD group. Costs of token accrual during Phase 1, in terms of number of trials and duration, showed a positive correlation with net tokens for the CD group but not the NCD group. Results are consistent with previous research demonstrating the value-enhancing effects of both prior contingent delivery and effort, and offer evidence that these histories influence sensitivity to loss. PMID- 27182089 TI - INTEGRATED MODELS OF SCHOOL-BASED PREVENTION: LOGIC AND THEORY. AB - School-based prevention programs can positively impact a range of social, emotional, and behavioral outcomes. Yet the current climate of accountability pressures schools to restrict activities that are not perceived as part of the core curriculum. Building on models from public health and prevention science, we describe an integrated approach to school-based prevention. These models leverage the most effective structural and content components of social-emotional and behavioral health prevention interventions. Integrated interventions are expected to have additive and synergistic effects that result in greater impacts on multiple student outcomes. Integrated programs are also expected to be more efficient to deliver, easier to implement with high quality and integrity, and more sustainable. We provide a detailed example of the process through which the PAX-Good Behavior Game and the Promoting Alternative Thinking Strategies (PATHS) curriculum were integrated into the PATHS to PAX model. Implications for future research are proposed. PMID- 27182090 TI - Estimating controlled direct effects of restrictivefeeding practices in the 'Early dieting in girls' study. AB - In this article, we examine the causal effect of parental restrictive feeding practices on children's weight status. An important mediator is children's self regulation status. Recent approaches interpret mediation effects based on the potential outcomes framework. Inverse probability weighting based on propensity scores are used to adjust for confounding and reduce the dimensionality of confounders simultaneously. We show that combining machine learning algorithms and logistic regression to estimate the propensity scores can be more accurate and efficient in estimating the controlled direct effects than using logistic regression alone. A data application shows that the causal effect of mother's restrictive feeding differs according to whether the daughter eats in the absence of hunger. PMID- 27182091 TI - Optimized Synthesis of a Pentafluoro-gem-diol and Conversion to a CF2Br Glucopyranose through Trifluoroacetate-Release and Halogenation. AB - Pentafluoro-gem-diols are substrates that enable the synthesis of valuable difluoromethylene-containing organic molecules through the release of trifluoroacetate. Currently, only one synthetic strategy is available to assemble these important precursors. Herein, two new synthetic strategies to a complex pentafluoro-gem-diol are compared to the existing route, and an improved synthetic route has completed. Moreover, the first synthesis of a CF2Br glucopyranose was finished by a tandem trifluoroacetate-release halogenation/cyclization protocol. PMID- 27182092 TI - A mild and efficient approach to enantioenriched alpha-hydroxyethyl alpha,beta unsaturated delta-lactams. AB - A straightforward approach toward enantioenriched alpha-substituted alpha,beta unsaturated delta-lactams is described. Although a considerable number of approches toward alpha,beta-unsaturated delta-lactams have been reported, there are relatively few examples of enantioenriched alpha,delta-disubstituted alpha,beta-unsaturated delta-lactams formation. The delta-stereocenter was formed by addition of allylmagnesium bromide to an N-tert-butylsulfinyl imine. The alpha,beta-unsaturated delta-lactam was furnished by ring-closing metathesis. Although Baylis-Hillman chemistry failed on this cyclic compound, introduction of the hydroxyethyl group prior to ring-closing metathesis was successful. A Baylis Hillman reaction was used to introduce the substituent at the alpha-position of the alpha,beta-unsaturated lactam. PMID- 27182093 TI - Panethnicity revisited: contested group boundaries in the post-9/11 era. AB - Existing theories of panethnicity in the USA concentrate on Asian Americans and Latinos, two umbrella groups that originally coalesced during the 1960s civil rights era. Although the role played by the state is recognized as central to panethnic development, we argue that the influence of this pivotal variable is contingent on historical context. Through a case study of emerging minority groups (Middle Eastern and South Asian Americans in the post-9/11 era), we re examine the existing conceptualization of panethnicity at a time when the state plays a more punitive than compensatory role. Using a methodology that draws on a range of novel sources, we document the way that pre-existing ethnic, religious and national-origin labels have been reinforced instead of panethnic labels for the populations under study. Accordingly, we develop an updated conceptualization of group formation that incorporates historical context and the role of the state in the post-9/11 era. PMID- 27182094 TI - Interpersonal Emotion Regulation Questionnaire (IERQ): Scale Development and Psychometric Characteristics. AB - Despite the popularity of emotion regulation in the contemporary literature, research has almost exclusively focused on only intrapersonal processes, whereas much less attention has been placed in interpersonal emotion regulation processes. In order to encourage research on interpersonal emotion regulation, we present a series of 4 studies to develop the Interpersonal Emotion Regulation Questionnaire (IERQ). The final scale consists of 20 items with 4 factors containing 5 items each. The 4 factors are: Enhancing Positive Affect; Perspective Taking; Soothing; and Social Modeling. The scale shows excellent psychometric characteristics. Implications for future research are discussed. PMID- 27182095 TI - Evaluation of immunohistochemical staining for glucagon in human pancreatic tissue. AB - Immunohistochemistry (IHC) and immunofluorescence (IF) staining techniques are important diagnostic tools of anatomic pathology in the clinical setting and widely used analytical tools in research laboratories. In diabetes research, they are routinely used for the assessment of beta- and alpha-cell mass, for assessment of endocrine cell distribution within the pancreas, for evaluation of islet composition and islet morphology. Here, we present the evaluation of IHC techniques for the detection of alpha-cells in human pancreatic tissue. We compared the Horse Radish Peroxidase (HRP)-based method utilizing DAB Peroxidase Substrate to the Alkaline Phosphatase (AP)-based method utilizing Vector Red substrate. We conclude that HRP-DAB staining is a robust and reliable method for detection of alpha-cells using either rabbit polyclonal or mouse monoclonal anti glucagon antibodies. However, AP-Vector Red staining should be used with caution, because it is affected by the dehydration with ethanol and toluene preceding the mounting of slides with Permount mounting medium. When AP-Vector Red is a preferable method for alpha-cell labeling, slides should be mounted using aqueous mounting medium or, alternatively, they could be air-dried before permanent mounting. PMID- 27182096 TI - Biomechanics Simulations Using Cubic Hermite Meshes with Extraordinary Nodes for Isogeometric Cardiac Modeling. AB - Cubic Hermite hexahedral finite element meshes have some well-known advantages over linear tetrahedral finite element meshes in biomechanical and anatomic modeling using isogeometric analysis. These include faster convergence rates as well as the ability to easily model rule-based anatomic features such as cardiac fiber directions. However, it is not possible to create closed complex objects with only regular nodes; these objects require the presence of extraordinary nodes (nodes with 3 or >= 5 adjacent elements in 2D) in the mesh. The presence of extraordinary nodes requires new constraints on the derivatives of adjacent elements to maintain continuity. We have developed a new method that uses an ensemble coordinate frame at the nodes and a local-to-global mapping to maintain continuity. In this paper, we make use of this mapping to create cubic Hermite models of the human ventricles and a four-chamber heart. We also extend the methods to the finite element equations to perform biomechanics simulations using these meshes. The new methods are validated using simple test models and applied to anatomically accurate ventricular meshes with valve annuli to simulate complete cardiac cycle simulations. PMID- 27182097 TI - Modeling sleep fragmentation in sleep hypnograms: An instance of fast, scalable discrete-state, discrete-time analyses. AB - Methods are introduced for the analysis of large sets of sleep study data (hypnograms) using a 5-state 20-transition-type structure defined by the American Academy of Sleep Medicine. Application of these methods to the hypnograms of 5598 subjects from the Sleep Heart Health Study provide: the first analysis of sleep hypnogram data of such size and complexity in a community cohort with a range of sleep-disordered breathing severity; introduce a novel approach to compare 5 state (20-transition-type) to 3-state (6-transition-type) sleep structures to assess information loss from combining sleep state categories; extend current approaches of multivariate survival data analysis to clustered, recurrent event discrete-state discrete-time processes; and provide scalable solutions for data analyses required by the case study. The analysis provides detailed new insights into the association between sleep-disordered breathing and sleep architecture. The example data and both R and SAS code are included in online supplementary materials. PMID- 27182098 TI - Adaptive importance sampling for network growth models. AB - Network Growth Models such as Preferential Attachment and Duplication/Divergence are popular generative models with which to study complex networks in biology, sociology, and computer science. However, analyzing them within the framework of model selection and statistical inference is often complicated and computationally difficult, particularly when comparing models that are not directly related or nested. In practice, ad hoc methods are often used with uncertain results. If possible, the use of standard likelihood-based statistical model selection techniques is desirable. With this in mind, we develop an Adaptive Importance Sampling algorithm for estimating likelihoods of Network Growth Models. We introduce the use of the classic Plackett-Luce model of rankings as a family of importance distributions. Updates to importance distributions are performed iteratively via the Cross-Entropy Method with an additional correction for degeneracy/over-fitting inspired by the Minimum Description Length principle. This correction can be applied to other estimation problems using the Cross-Entropy method for integration/approximate counting, and it provides an interpretation of Adaptive Importance Sampling as iterative model selection. Empirical results for the Preferential Attachment model are given, along with a comparison to an alternative established technique, Annealed Importance Sampling. PMID- 27182099 TI - Pyran Template Approach to the Design of Novel A3 Adenosine Receptor Antagonists. AB - [Table: see text] A3 adenosine receptor antagonists have potential as anti inflammatory, anti-asthmatic, and anti-ischemic agents. We previously reported the preparation of chemical libraries of 1,4-dihydropyridine (DHP) and pyridine derivatives and identification of members having high affinity at A3 adenosine receptors. These derivatives were synthesized through standard three-component condensation/oxidation reactions, which permitted versatile ring substitution at five positions, i.e., the central ring served as a molecular scaffold for structurally diverse substituents. We extended this template approach from the DHP series to chemically stable pyran derivatives, in which the ring NH is replaced by O and which is similarly derived from a stepwise reaction of three components. Since the orientation of substituent groups may be conformationally similar to the 1,4-DHPs, a direct comparison between the structure activity relationships of key derivatives in binding to adenosine receptors was carried out. Affinity at human A3 receptors expressed in CHO cells was determined vs. binding of [125I]AB-MECA (N6-(4-amino-3-iodobenzyl)-5'-N-methyl carbamoyladenosine). There was no potency-enhancing effect, as was observed for DHPs, of 4-styryl, 4-phenylethynyl, or 6-phenyl substitutions. The most potent ligands in this group in binding to human A3 receptors were 6-methyl and 6-phenyl analogs, 3a (MRS 1704) and 4a (MRS 1705), respectively, of 3,5-diethyl 2-methyl-4 phenyl-4H-pyran-3,5-dicarboxylate, which had Ki values of 381 and 583 nM, respectively. These two derivatives were selective for human A3 receptors vs. rat brain A1 receptors by 57-fold and 24-fold, respectively. These derivatives were inactive in binding at rat brain A2A receptors, and at recombinant human A2B receptors displayed Ki values of 17.3 and 23.2 MUM, respectively. The selectivity, but not affinity, of the pyran derivatives in binding to the A3 receptor subtype was generally enhanced vs. the corresponding DHP derivatives. PMID- 27182100 TI - Rapid learning of associations between sound and action through observed movement. A TMS study. AB - Research has established that there is a cognitive link between perception and production of the same movement. However, there has been relatively little research into the relevance of this for non-expert perceivers, such as music listeners who do not play instruments themselves. In two experiments we tested whether participants can quickly learn new associations between sounds and observed movement without performing those movements themselves. We measured motor evoked potentials (MEPs) in the first dorsal interosseous muscle of participants' right hands while test tones were heard and single transcranial magnetic stimulation (TMS) pulses were used to trigger motor activity. In Experiment 1 participants in a 'human' condition (n=4) learnt to associate the test tone with finger movement of the experimenter, while participants in a 'computer' condition (n=4) learnt that the test tone was triggered by a computer. Participants in the human condition showed a larger increase in MEPs compared with those in the computer condition. In a second experiment pairing between sounds and movement occurred without participants repeatedly observing the movement and we found no such difference between the human (n=4) and computer (n=4) conditions. These results suggest that observers can quickly learn to associate sound with movement, so it should not be necessary to have played an instrument to experience some motor resonance when hearing that instrument. PMID- 27182101 TI - Titanocene-Gold Complexes Containing N-Heterocyclic Carbene Ligands Inhibit Growth of Prostate, Renal, and Colon Cancers in Vitro. AB - We report on the synthesis, characterization, and stability studies of new titanocene complexes containing a methyl group and a carboxylate ligand (mba = OC(O)-p-C6H4-S-) bound to gold(I)-N-heterocyclic carbene fragments through the thiolate group: [(eta5-C5H5)2TiMe(MU-mba)Au(NHC)]. The cytotoxicities of the heterometallic compounds along with those of novel monometallic gold-N heterocyclic carbene precursors [(NHC)Au(mbaH)] have been evaluated against renal, prostate, colon, and breast cancer cell lines. The highest activity and selectivity and a synergistic effect of the resulting heterometallic species was found for the prostate and colon cancer cell lines. The colocalization of both titanium and gold metals (1:1 ratio) in PC3 prostate cancer cells was demonstrated for the selected compound 5a, indicating the robustness of the heterometallic compound in vitro. We describe here preliminary mechanistic data involving studies on the interaction of selected mono- and bimetallic compounds with plasmid (pBR322) used as a model nucleic acid and the inhibition of thioredoxin reductase in PC3 prostate cancer cells. The heterometallic compounds, which are highly apoptotic, exhibit strong antimigratory effects on the prostate cancer cell line PC3. PMID- 27182102 TI - Two-photon in vivo flow cytometry using a fiber probe. AB - We have demonstrated the use of a double-clad fiber probe to conduct two-photon excited flow cytometry in vitro and in vivo. We conducted two-channel detection to measure fluorescence at two distinct wavelengths simultaneously. Because the scattering and absorption problems from whole blood were circumvented by the fiber probe, the detected signal strength from the cells were found to be similar in PBS and in whole blood. We achieved the same detection efficiency of the membrane-binding lipophilic dye DiD labeled cells in PBS and in whole blood. High detection efficiency of green fluorescent protein (GFP)-expressing cells in whole blood was demonstrated. DiD-labeled untransfected and GFP-transfected cells were injected into live mice and the circulation dynamics of the externally injected cells were monitored. The detection efficiency of GFP-expressing cells in vivo was consistent with that observed in whole blood. PMID- 27182104 TI - 'Marge': a European Elderberry for North American Producers. AB - Elderberries are being increasingly produced and consumed in North America for their edible and medicinal flowers and fruits. The American elderberry (Sambucus nigra subsp. canadensis) is native to, and most often cultivated in North America. The European elderberry (S. nigra subsp. nigra) has been developed into an economically-important horticultural crop in Europe, but most European cultivars do not perform well in the midwestern USA. The genotype S. nigra subsp. nigra 'Marge' is an open-pollinated seedling of S. nigra subsp. nigra 'Haschberg', which is one of the most popular elderberry cultivars grown in Europe. In a four-year study (one establishment year followed by 3 production years; 2008-2011) at three Missouri (USA) locations, 'Marge' significantly out performed and out-yielded eight American elderberry genotypes within the same replicated field plots. Across 3 production years at all three sites, 'Marge' achieved budbreak later, flowered earlier, suffered less Eriophyid mite damage, was taller, produced larger berries, and yielded significantly greater amounts of fruit compared with all eight American elderberry genotypes in the study. At one site, 'Marge' produced three times the yield (1.89 kg/plant) compared with the next highest-producing American elderberry genotype (0.65 kg/plant). It is an exceptionally robust and drought-resistant elderberry. The phenotypic attributes of 'Marge' are similar to that of European elderberry except that it performs exceptionally well in the midwestern USA. DNA marker results, along with phenological and morphological characteristics, indicate that 'Marge' is a European elderberry (S. nigra subsp. nigra). As with most European genotypes, 'Marge' does not fruit on first-year wood, and will therefore require a different pruning regimen compared with American elderberry for success in North American production. We do not yet know how 'Marge' will perform outside the midwestern USA, but it is so productive, unique, and mite resistant, that it merits introduction as a cultivar. PMID- 27182103 TI - The relationship between testosterone and long-distance calling in wild male chimpanzees. AB - Long-distance calling is a common behaviour in animals that has various important social functions. At a physiological level, calling is often mediated by gonadal hormones such as testosterone (T), particularly when its function is linked to intra-sexual competition for mates or territory. T also plays an important role in the development of vocal characteristics associated with dominance in humans. However, the few available studies of T and vocal behaviour in non-human primates suggest that in primates T has less influence on call production than in other animals. We tested this hypothesis by studying the relationship between T concentrations and pant hooting in wild male chimpanzees (Pan troglodytes schweinfurthii) of the Kanyawara community in the Kibale National Park, Uganda. We found three kinds of correlation. Hourly T averages were positively associated with hourly rates of pant-hooting. Monthly T levels were likewise correlated with monthly rates of pant hooting after controlling for other influences such as fission-fusion rates. Finally, males with high T levels had higher peak frequency at the start of the call climax. These results suggest that T affects the production of pant-hoots in chimpanzees. This implies that the pant-hoot call plays a role in male-male competition. We propose that even in cognitively sophisticated species, endocrine mechanisms can contribute to regulating vocal production. PMID- 27182105 TI - Conditional Effects of Appearance and Performance Enhancing Drugs (APEDs) Use on Mood in Powerlifters and Bodybuilders. AB - Risk factors for steroid mood effects are unclear and few studies have examined drugs used concurrently with steroids (e.g., stimulants) or emotion regulation deficits that may have unique mood effects. We examined effects of steroid use, stimulant use, and history of mood, trauma, or anxiety disorders on mood in 130 men via online survey. Both steroid and stimulant use had few unique effects on mood. However, stimulant use was associated with increased negative affect and decreased automatic positive thoughts among individuals with a history of mood, trauma, or anxiety disorders. Results highlight the importance of patient differences in steroid effects. PMID- 27182106 TI - Effects of Endogenous Salicylic Acid During Calcium Deficiency-Induced Tipburn in Chinese Cabbage (Brassica rapa L. ssp. pekinensis). AB - By cultivating tipburn-susceptible plants in modified Hoagland's medium containing of gradient exogenous calcium (Ca2+), we have shown that Ca2+ deficiency is one of the main causes of tipburn in Chinese cabbage (Brassica rapa L. ssp. pekinensis). The effect of endogenous plant Ca2+ concentrations on tipburn was also studied in a doubled haploid (DH) population consisting of 100 individuals, but no correlation was found. We then examined the expression of 12 Ca2+ transporter genes that function in cytosolic Ca2+ homeostasis in both tipburn-susceptible and tipburn-resistant plants under normal and tipburn inducing conditions. Expression patterns for most of these genes differed between the two types of plants. Salicylic acid (SA) accumulated in response to conditions of calcium deficiency in our study, and both total SA and SA beta glucoside (SAG) in tipburn-susceptible plants was ~3-fold higher than it was in resistant plants following Ca2+ deficiency treatment. Also, the changes observed in SA levels correlated well with cell death patterns revealed by trypan blue staining. Therefore, we speculate that the cytoplasmic Ca2+ fluctuation-induced downstream signaling events, as well as SA signaling or other biological events, are involved in the plant defense response to tipburn in Chinese cabbage. PMID- 27182107 TI - Expression of IPT in Asakura-sanshoo (Zanthoxylum piperitum (L.) DC. f. inerme Makino) Alters Tree Architecture, Delays Leaf Senescence, and Changes Leaf Essential Oil Composition. AB - The IPT gene encodes isopentenyl pyrophosphate transferase, a key enzyme in cytokinin biosynthesis. We introduced IPT under the control of the CaMV35S promoter into Asakura-sanshoo (Zanthoxylum piperitum (L.) DC. f. inerme Makino) via stable Agrobacterium tumefaciens-mediated transformation. Three of 3-year-old transgenic Asakura-sanshoo lines Y5, Y16, and Y17 were used to evaluate the effects of IPT expression on the morphological characteristics, leaf senescence, and essential oil composition. Introduced IPT into Asakura-sanshoo stimulated an increase in cytokinin content and a decrease in auxin level. The increase in the cytokinin/auxin ratio affected the tree architecture in 3-year-old transgenic lines. The phenotypes of transgenic lines included reduced stem elongation, decreased leaf surface area, increased branching, and delayed leaf senescence. The expression of IPT in Asakura-sanshoo also affected the leaf essential oil composition. The amount of oxygenated sesquiterpenoid compounds in Y5 and Y16 was 21.1 and 15.8 % higher, respectively, than that in wild type (WT). The amount of aromatic compounds in Y5 and Y16 was 2.9 and 24.6 % lower, respectively, than that in WT. These results show that ipt expression in Asakura-sanshoo conferred desirable traits, including a dwarf growth habit, delayed senescence, and increased concentrations of some sesquiterpenoid compounds. PMID- 27182108 TI - Longitudinal Associations between Anhedonia and Internet-Related Addictive Behaviors in Emerging Adults. AB - Internet addiction (including online gaming) has been associated with depression. However, most prior research relating internet addiction symptomatology to depressive symptoms has been cross-sectional, conducted with children and adolescents, and only examined depressive symptoms as a broad construct. The purpose of the current study was to examine potential longitudinal associations between anhedonia (i.e., difficulty experiencing pleasure, a key facet of depression) and internet-related addictive behaviors in 503 at-risk emerging adults (former attendees of alternative high schools). Participants completed surveys at baseline and approximately one year later (9-18 months later). Results indicated that trait anhedonia prospectively predicted greater levels of compulsive internet use and addiction to online activities as well as a greater likelihood of addiction to online/offline video games. These findings suggest that anhedonia may contribute to the development of internet-related addictive behaviors in the emerging adult population. Thus, interventions that target anhedonia in emerging adulthood (e.g., bupropion treatment or behavioral activation therapy) may help prevent or treat internet addiction. PMID- 27182110 TI - 3D Magnetic Induction Maps of Nanoscale Materials Revealed by Electron Holographic Tomography. AB - The investigation of three-dimensional (3D) ferromagnetic nanoscale materials constitutes one of the key research areas of the current magnetism roadmap and carries great potential to impact areas such as data storage, sensing, and biomagnetism. The properties of such nanostructures are closely connected with their 3D magnetic nanostructure, making their determination highly valuable. Up to now, quantitative 3D maps providing both the internal magnetic and electric configuration of the same specimen with high spatial resolution are missing. Here, we demonstrate the quantitative 3D reconstruction of the dominant axial component of the magnetic induction and electrostatic potential within a cobalt nanowire (NW) of 100 nm in diameter with spatial resolution below 10 nm by applying electron holographic tomography. The tomogram was obtained using a dedicated TEM sample holder for acquisition, in combination with advanced alignment and tomographic reconstruction routines. The powerful approach presented here is widely applicable to a broad range of 3D magnetic nanostructures and may trigger the progress of novel spintronic nonplanar nanodevices. PMID- 27182109 TI - Emergence and Utility of Nonspherical Particles in Biomedicine. AB - The importance of the size of targeted, spherical drug carriers has been previously explored and reviewed. Particle shape has emerged as an equally important parameter in determining the in vivo journey and efficiency of drug carrier systems. Researchers have invented techniques to better control the geometry of particles of many different materials, which have allowed for exploration of the role of particle geometry in the phases of drug delivery. The important biological processes include clearance by the immune system, trafficking to the target tissue, margination to the endothelial surface, interaction with the target cell, and controlled release of a payload. The review of current literature herein supports that particle shape can be altered to improve a system's targeting efficiency. Non-spherical particles can harness the potential of targeted drug carriers by enhancing targeted site accumulation while simultaneously decreasing side effects and mitigating some limitations faced by spherical carriers. PMID- 27182111 TI - Stress-reactive rats (high-avoidance female rats) have a shorter lifespan than stress-nonreactive rats (low-avoidance female rats). AB - Although Hatano high-avoidance and low-avoidance rats (HAA and LAA, respectively) have been selectively bred for good versus poor avoidance learning, HAA rats are known to be more reactive to stress than LAA rats. In this study, HAA and LAA female rats were compared during reproductive aging by observing estrous cycles from 8 to 11 months of age. Furthermore, these rats were allowed to live out their natural lifespans, that is, until 24 months of age, in order to compare their survival and to clarify the relationship between reproductive aging and tumor development. At eight months of age, 2 of 35 HAA rats and 20 of 35 LAA rats had abnormal estrous cycles. The median lifespan of the HAA rats (673 days) was shorter than that of the LAA rats (733 days). The incidence of pituitary neoplasia was higher in the HAA rats than in the LAA rats. These results suggest that HAA female rats (i.e., stress-reactive rats) have a shorter lifespan than LAA female rats (i.e., stress-nonreactive rats) and develop pituitary neoplasia, which was one of the causal factors in their accelerated mortality. However, the onset of an age-matched abnormal cycle did not correspond with their lifespan. PMID- 27182112 TI - Evaluation of potential activity of luseogliflozin on vascular proliferation in the mesenteric lymph node with or without vascular tumors in Sprague-Dawley rats in a carcinogenicity study. AB - The incidence of mesenteric lymph node vascular tumors can vary in rats, and appropriate assessment of potential risk of tumorigenicity is needed when the incidence is higher in treated groups than in a control group. In a 2-year rat carcinogenicity study of luseogliflozin, a selective sodium-dependent glucose co transporter 2 inhibitor for the treatment of type 2 diabetes mellitus, there was a slight but statistically significant increase in the total number of hemangiomas and hemangiosarcomas in the mesenteric lymph nodes in males at a high dose. As part of the risk assessment for luseogliflozin, its effect on the vascular proliferation potential in the mesenteric lymph nodes was examined in a rat carcinogenicity study by performing an image analysis using specimens with double immunohistochemical staining for PCNA and CD34 in control and high-dose males. In addition, immunohistochemical staining for VEGF was performed to detect enhanced angiogenesis. In the high-dose males that did not have a hemangioma/hemangiosarcoma, neither an increased number of PCNA/CD34-positive cells nor changes in the expression pattern of VEGF was observed. On the other hand, in the high-dose males that had a hemangioma/hemangiosarcoma, the number of PCNA-positive cells was increased in the tumor areas, and the number in the hemangioma/hemangiosarcoma was approximately one-half of that in the hemangiosarcoma in the control male. In conclusion, no potential change leading to vascular proliferation/tumors was detected in the mesenteric lymph nodes of high-dose males receiving luseogliflozin. PMID- 27182114 TI - Keishibukuryogan is not carcinogenic in Sprague-Dawley rats. AB - Keishibukuryogan is a traditional Japanese medicine widely administered to patients with menopausal symptoms. Because humans use it on a long-term basis, we believed that a carcinogenicity study was warranted. We orally administered keishibukuryogan (TJ-25) extract powder to 6-week-old Sprague-Dawley rats [Crl:CD(SD)], which were divided into four dosage groups-0 (water for injection), 100, 500 and 2,500 mg/kg/day for 24 months. We found that TJ-25 did not affect the survival rate of either sex. Furthermore, it did not affect the clinical condition of the rats, number of superficial tumors found by palpation, body weight, food consumption, hematology, or gross pathological findings. The severity of degeneration of muscle fiber in the femoral skeletal muscle increased slightly in males and females in the 2,500 mg/kg/day group, but TJ-25 did not increase the number of tumors found on histopathological examination. In our study, oral administration of TJ-25 extract powder in rats for 24 months was not associated with an increased incidence of tumors. PMID- 27182115 TI - Spontaneous malignant myoepithelioma of the maxillary gland in a young adult male BALB/c F1 hybrid mouse. AB - A spontaneous tumor was observed in the maxillary gland of a 12-week-old male BALB/c F1 hybrid mouse. Histopathologically, the tumor invaded both the nasal cavity and maxillary sinus, and ethmoturbinates were destroyed. The majority of the tumor cells had oval nuclei with eosinophilic and vacuolar cytoplasm. Numerous mitotic figures and necrotic foci were also observed throughout the tumor. Immunohistochemically, almost all of the tumor cells were strongly positive for cytokeratin (WSS) and alpha-smooth muscle actin. However, tumor cells were negative for cytokeratin (CAM 5.2), suggesting that these tumor cells originated from myoepithelial cells. The present tumor was diagnosed as a malignant myoepithelioma of the maxillary gland. This is the first report describing spontaneous malignant myoepithelioma in the maxillary gland of a young adult BALB/c F1 hybrid mouse. PMID- 27182113 TI - Establishment of a mouse model for pulmonary inflammation and fibrosis by intratracheal instillation of polyhexamethyleneguanidine phosphate. AB - Although several animal models have been developed to study human pulmonary fibrosis, lack of a perfect model has raised the need for various animal models of pulmonary fibrosis. In this study, we evaluated the pulmonary effect of polyhexamethyleneguanidine phosphate instillation into the lungs of mice to determine the potential of these mice as a murine model of pulmonary fibrosis. Intratracheal instillation of polyhexamethyleneguanidine phosphate induced severe lung inflammation manifested by the infiltration of mononuclear cells and neutrophils and increased production of IL-6, TNF-alpha, CCL2 and CXCL1. The lung inflammation gradually increased until 28 days after polyhexamethyleneguanidine phosphate exposure, and increases of collagen deposition and TGF-beta production, which are indicators of pulmonary fibrosis, were seen. Our study showed that intratracheal instillation of polyhexamethyleneguanidine phosphate induces pulmonary inflammation and fibrosis in mice. PMID- 27182116 TI - Histopathology of a wavy medaka. AB - Wavy medakas are medakas that exhibit spinal curvature characterized by dorsoventrally curved vertebrae. We found a spontaneous wavy medaka in our experimental stock and subjected it to a histopathological examination. Macroscopically, the wavy medaka's spine formed an M shape, and its vertebrae displayed a dorsoventral curvature that started at the third vertebral bone. Microscopically, the vertebral cavities were filled with fibrous tissue, which was similar to that seen in the central parts of the intervertebral discs of a normal medaka. The vertebral joints were composed of vacuolated notochord cells without intervertebral disc formation. These changes were also observed in the caudal region, which exhibited less curvature. In the normal medaka, the intervertebral discs form via the regression of the notochord that plays a key role in the development of vertebrae and disc formation. We concluded that notochordal subinvolution had induced intervertebral disc dysplasia, leading to lordokyphosis, in the wavy medaka. PMID- 27182117 TI - Spontaneous cutaneous soft tissue sarcoma with differentiation into fibroblasts in a Sprague-Dawley rat. AB - A small mass with an ulcer was found in the skin of the dorsal cervix of a 7 month-old male Sprague-Dawley rat. Histologically, the central region of the tumor showed a high cellular density with oval-shaped tumor cells arranged in an alveolar pattern and thin collagen fiber bundles. The peripheral region of the tumor had a low cellular density with short spindle- or polygonal-shaped tumor cells surrounded by abundant collagen fiber bundles. Immunohistochemically, the tumor cells were strongly positive for vimentin and proliferating cell nuclear antigen, and a portion of the short spindle- or polygonal-shaped cells located in the peripheral region of the tumor were positive for S100A4. However, the tumor cells were negative for alpha-smooth muscle actin, desmin, S100, chromogranin A, neurofilament, CD68, Iba-1, cytokeratin 20, von Willebrand factor, melanosome, and anti-melanoma. Electron microscopically, the tumor cells had an abundance of rough endoplasmic reticulum, the Golgi apparatus, and a few intracellular collagen fibrils, showing fibroblastic features. Considering the lack of diagnostic differentiation, the tumor was diagnosed as an undifferentiated malignant mesenchymal tumor and classified as a soft tissue sarcoma with differentiation into fibroblasts in a portion of the tumor cells. PMID- 27182118 TI - Histopathological characteristics of renal changes in human renin-angiotensinogen double transgenic rats. AB - The human renin-angiotensinogen double transgenic rat (dTGR) is a model of hypertension. The aim of this short report was to describe the histopathological characteristics of the renal changes in this rat strain in detail. Seven to nine week-old male dTGRs were euthanized, and their kidneys were histopathologically examined. At the time of sacrifice, the average systolic blood pressure of the dTGRs was 258 mmHg, while that of age-matched, normal Sprague-Dawley rats was 135 mmHg. In the kidney, histopathological changes were observed mainly in blood vessels, tubules and glomeruli. In blood vessels, changes including medial hypertrophy, intimal thickening, hyaline change and/or fibrinoid necrosis were observed in arteries and arterioles. In tubules, changes including tubular basophilia were observed radially, mainly around interlobular arteries with lesions. In glomeruli, changes including hyaline droplet accumulation in podocytes, which was accompanied by increased expression of desmin, were observed. These changes were similar to those reported in other hypertension models, such as the spontaneously hypertensive rat (SHR). We hope that this short report will be helpful in histopathological examination of renal changes in this or other hypertension models. PMID- 27182119 TI - Increased MFG-E8 expression and its implications in the vascular pathophysiology of cocaine abuse. AB - The aim of this study was to examine the possible involvement of smooth muscle cell remodeling and the induction of MFG-E8 (milk fat globule protein epidermal growth factor-VIII) in vascular pathophysiology during cocaine administration in cultured cells and rats. Cocaine exerts bifurcate effects on vascular cells; it stimulates vasoconstriction through enhancement of catecholamine release at low doses, while it suppresses cardiovascular functions through inhibition of ion channels at high doses. Short-term exposure to a high concentration of cocaine (3 mM, 24 hr) resulted in cell death of A7r5 rat aorta-derived smooth muscle cells. On the other hand, long-term exposure of the same cells to a low concentration (0.3 mM, ~7 days) resulted in a transient increase in MFG-E8 expression followed by an increased tendency toward cyclin D1, PCNA (proliferating cell nuclear antigen), and CDK4 (cyclin-dependent protein kinase-4) expression. Interestingly, autophagy was not induced, but rather was impaired, in cocaine-treated cells. Increased expressions of MFG-E8, PCNA, and CDK4 were also observed in the aortic vascular cells of rats administered cocaine (50 mg/kg, 2 days, i.v.), confirming that cocaine induced MFG-E8 expression in vivo. Taken together, the results show that MFG-E8 is induced in vascular cells exposed to cocaine, and that this induction is likely to be involved in the vascular toxicity elicited by cocaine abuse. PMID- 27182121 TI - Erratum. AB - [This corrects the article on p. 223 in vol. 24.]. PMID- 27182120 TI - Transient effects of empty liposomes on hepatic macrophage populations in rats. AB - Liposomes have been used as a vehicle for encapsulating chemicals or toxins in toxicological studies. We investigated the transient effects of empty liposomes on hepatic macrophages by applying a single intravenous injection at a dose of 10 ml/kg body weight in 6-week-old male F344 rats. One day after injection, the numbers of hepatic macrophages reacting to CD163, CD68, Iba-1, MHC class II, Gal 3 and CD204 were significantly increased in liposome-treated rats. CD163(+) Kupffer cells and CD68(+) macrophages with increased phagocytic activity in hepatic lobules were most sensitive. The histological architecture of the liver was not changed following liposome injection; however, hepatocytes showed increased proliferating activity, demonstrable with proliferation marker immunostaining and by an increase in gene profiles related to the cell cycle. In the liposome-treated rats, interestingly, AST and ALT values were significantly decreased, and MCP-1, IL-1beta and TGF-beta1 mRNAs were significantly increased. Collectively, the present study found that hepatic macrophages activated by liposomes can influence liver homeostasis. This information would be useful for background studies on liposomes. PMID- 27182122 TI - Covariant Image Representation with Applications to Classification Problems in Medical Imaging. AB - Images are often considered as functions defined on the image domains, and as functions, their (intensity) values are usually considered to be invariant under the image domain transforms. This functional viewpoint is both influential and prevalent, and it provides the justification for comparing images using functional Lp -norms. However, with the advent of more advanced sensing technologies and data processing methods, the definition and the variety of images has been broadened considerably, and the long-cherished functional paradigm for images is becoming inadequate and insufficient. In this paper, we introduce the formal notion of covariant images and study two types of covariant images that are important in medical image analysis, symmetric positive-definite tensor fields and Gaussian mixture fields, images whose sample values covary i.e., jointly vary with image domain transforms rather than being invariant to them. We propose a novel similarity measure between a pair of covariant images considered as embedded shapes (manifolds) in the ambient space, a Cartesian product of the image and its sample-value domains. The similarity measure is based on matching the two embedded low-dimensional shapes, and both the extrinsic geometry of the ambient space and the intrinsic geometry of the shapes are incorporated in computing the similarity measure. Using this similarity as an affinity measure in a supervised learning framework, we demonstrate its effectiveness on two challenging classification problems: classification of brain MR images based on patients' age and (Alzheimer's) disease status and seizure detection from high angular resolution diffusion magnetic resonance scans of rat brains. PMID- 27182123 TI - Silymarin content in Silybum marianum populations growing in Egypt. AB - Chemical variation of Silybum marianum growing in the north, middle, and south of Egypt was investigated. Variation was assessed according to the content of the individual silymarin components in the fruits of the plant. The fruits were distinguished according to location, plant variety, and fruit color (maturity). Accelerated solvent extraction was used to standardize the silymarin extraction. Quantitative analysis of the content of silymarin components was carried out using HPLC with qNMR-controlled reference standards of taxifolin and seven major flavonolignans including silybin A, silybin B, isosilybin A, isosilybin B, silychristin, isosilychristin, and silydianin. The quantification method was validated in accordance with ICH guidelines. Principal component analysis and hierarchical clustering were carried out to create homogeneous clusters of samples based on the content of the silymarin components. Taxifolin had the lowest correlation relative to other silymarin components, whereas silybin A was positively correlated with silybin B. The samples clustered into three classes: silydianin-rich samples, samples with an average silymarin content of <18.8 mg/g, and one class enriched in silymarin (>18.8 mg/g). S. marianum growing in the Nile delta showed the highest silymarin content. No correlation was found between fruit color and silymarin content, indicating that the fruit maturity stage has no significance. PMID- 27182124 TI - Evaluating life in foster homes for persons with serious mental illness: Resident and caregiver perspectives. AB - BACKGROUND: In Montreal Canada, the majority of persons with serious mental illness discharged from psychiatric hospitals were placed into foster homes. Very little updated information exists on life in foster homes, and the level of autonomy allowed in this residential setting. AIMS: The purpose of the study was to elicit the foster home residents' opinions about their lives in this setting and their caregiver's perception of the level of autonomy allowed. METHOD: Two questionnaires were administered to 102 foster home residents and their caregivers: (1) Patient Attitude Questionnaire and (2) Hospital and Hostel Practices Profile Survey. RESULTS: Consumers are satisfied living in this type of milieu and do not desire to change their housing. The foster home provides residents with a sense of security and well being. Foster homes rank second in terms of autonomy when compared to hospitals and hostels. Only supported apartments rank higher. CONCLUSION: These findings shed a new light on this type of residential milieu. Over time the structure of foster homes has evolved. This study points to the need to value the opinions of consumers and not force people to move onto other types of housing. PMID- 27182125 TI - The promises of big data and small data for travel behavior (aka human mobility) analysis. AB - The last decade has witnessed very active development in two broad, but separate fields, both involving understanding and modeling of how individuals move in time and space (hereafter called "travel behavior analysis" or "human mobility analysis"). One field comprises transportation researchers who have been working in the field for decades and the other involves new comers from a wide range of disciplines, but primarily computer scientists and physicists. Researchers in these two fields work with different datasets, apply different methodologies, and answer different but overlapping questions. It is our view that there is much, hidden synergy between the two fields that needs to be brought out. It is thus the purpose of this paper to introduce datasets, concepts, knowledge and methods used in these two fields, and most importantly raise cross-discipline ideas for conversations and collaborations between the two. It is our hope that this paper will stimulate many future cross-cutting studies that involve researchers from both fields. PMID- 27182126 TI - Pattern of induced estrus and conception rate following Ovsynch and Ovsynch based gonadotropin-releasing hormone treatments initiated on day 6 of estrous cycle in repeat breeding crossbred cows. AB - AIM: The aim was to evaluate the estrus response, incidence of accessory corpus luteum formation and fertility following different hormonal protocols in repeat breeding crossbred cows. MATERIALS AND METHODS: This study was carried out on 24 repeat breeding crossbred cows allotted into four groups. Cows of Group I was not given any treatment, Group II was treated with gonadotropin-releasing hormone (GnRH) injection on day 6 post-estrus, Group III was treated with Ovsynch protocol, and Group IV was treated with Ovsynch based GnRH treatment. Estrus responses such as duration, onset, percentage, and intensity of estrus were recorded during the study. The incidence of accessory corpus luteum was recorded per rectally on day 7 after first and additional GnRH of Ovsynch treatment. The conception rate for all groups was calculated by the absence of estrus and on day 45 after artificial insemination (AI) per rectum. Serum samples were collected at AI and day 12 post-AI in Group I and II. Serum samples were also collected at GnRH, Prostaglandin F2alpha (PGF2alpha), timed AI (TAI) and day 12 post-TAI in Group III and IV. RESULTS: Ovsynch and Ovsynch based GnRH treatments are resulted in 100.00% induction of estrus after the PGF2alpha injection. Onset of induced estrus after the PGF2alpha injection for Group III and IV was recorded as 48.750+/-0.713 and 51.472+/-1.989 h, respectively, and it was not significant. There was no significant difference in duration of estrus among the groups. The incidence of intermediate estrus intensity was found to be highest. All the cows showed the incidence of formation of accessory corpus luteum subsequent to GnRH treatment on day 6 of the estrous cycle in Group II, III, and IV. The conception rate was 0.00%, 16.67%, 50.00%, and 50.00% in Group I, II, III, and IV, respectively. CONCLUSION: Ovsynch and Ovsynch based GnRH treatments initiated on day 6 of estrous cycle capable of responding with a higher percentage of ovulation and formation of accessory corpus luteum which helped in higher conception rate over single post-AI GnRH treatment in repeat breeders. These treatments responded with better estrus response but did not significantly improve estrus intensity. PMID- 27182127 TI - Study on development of accessory sex glands in prepubertal kids using two dimensional ultrasonography. AB - AIM: The present study was undertaken to study growth pattern of accessory sex glands in prepubertal kids from 2 weeks to 6 months of age using two-dimensional ultrasonography. MATERIALS AND METHODS: The study was conducted on six Beetal kids. The scanning of accessory sex glands was done in standing position using rectal probe and measurements were recorded. Data collected were statistically analyzed using one-way ANOVA followed by Duncan multiple range test was performed using the SPSS (16.0) system for windows. RESULTS: With the advancement of age all the dimensions of glands increased. Both the lobes of prostate gland showed an increase in width with advancement of age. Width of prostate above the urethra (W1) showed a significant increase at 2, 10, and 20 weeks of age, whereas non significant increase from 2 to 8, 10 to 19, and 20 to 24 weeks of age was recorded. Width of prostate below the urethra (W2) showed a significant increase at 20 weeks of age, whereas non-significant increase was recorded during rest of period of growth. Left and right bulbourethral gland showed a similar pattern of growth with the advancement of age. The circumference dimensions increased significantly at 2, 16, 20, and 21 weeks of age for both glands. The increase was non-significant from 4 to 14, 16 to 19, and 20 to 23 weeks of age. The same pattern was observed for left and right seminal vesicular gland. CONCLUSION: Significant growth in three accessory sex glands in prepubertal kids was not observed at the same age. The trend observed was that the prostate was the first gland to show significant growth at 10 weeks of age followed by a significant increase in seminal vesicles and bulbourethral gland at 14 and 16 weeks of age, respectively. PMID- 27182128 TI - Genetic and environmental causes of variation in gestation length of Jersey crossbred cattle. AB - AIM: The objective of this study was to investigate the effect of genetic and non genetic factors and estimate the genetic parameter for gestation length (GL) of Jersey crossbred cattle. MATERIALS AND METHODS: The data included the 986 parturition records on Jersey crossbred cattle maintained at the Eastern Regional Station of ICAR-National Dairy Research Institute, Kalyani, West Bengal, India during 36 years (1978-2013). The data were analyzed applying mixed model least square technique considering the fixed effects of genetic group, season of calving, period of calving, parity of animal, birth weight, and sex of calf born from animal. The effect of sire was included as a random effect in the model. RESULTS: The genetic group of animal, season of calving, parity of animal, and birth weight of calf born were found to be a significant source of variation in the GL, whereas the period of calving and sex of calf did not affect this trait. Cows with <50% and >62.5% Jersey inheritance had the shortest and longest GLs, respectively. Cows calved in summer and rainy season had shorter GL than those calved in the winter season. Older cows in 4(th) parity carried calves for longer days than the cows in 1(st) parity. The increase in calf birth weight significantly (p<0.01) contributed to a linear increase in GL value in this study. The heritability estimate of GL was 0.24+/-0.08. CONCLUSION: It can be concluded that selection for lower GL without distressing future growth of calf can be used to reduce calving difficulty, but a very small standard deviation of GL limits the benefit. Moreover, more accurate prediction of calving date will help in better management and health care of pregnant animals. PMID- 27182129 TI - Neonatal mortality in dogs: Prognostic value of Doppler ductus venosus waveform evaluation - Preliminary results. AB - AIM: To define the prognostic value of Doppler ultrasonographic morphology of ductus venosus (DV) waveform on canine neonatal mortality. MATERIALS AND METHODS: Fifty-four healthy pregnant bitches underwent fetal ultrasonographic assessment. The DV waveforms were classified as diphasic (dDVw) or triphasic (tDVw) and compared with neonatal mortality. RESULTS: Ninety-three fetuses were evaluated. Twenty fetuses belonged to litters with neonatal mortality, in which tDVw was observed. Seven fetuses belonged to litters without neonatal mortality, in which tDVw was observed. Fifty-eight fetuses belonged to litters without neonatal mortality, in which only dDVw was observed. Eight fetuses belonged to litters with neonatal mortality, in which only dDVw was observed. The correlation between tDVw and neonatal mortality was statistically significant (odds ratio [OR], 20.7; p<0.0001). Considering only pregnancies with one or two fetuses with the same DV waveform: Two fetuses with tDVw belonged to litters with neonatal mortality; 1 foetus with tDVw belonged to litter without neonatal mortality and 26 fetuses showed dDVw without neonatal mortality. The correlation between tDVw and neonatal mortality even in litters up to two pups was statistically significant (OR, 88.3; p=0.01). CONCLUSION: Echo-Doppler assessment of DV is feasible in canine fetuses, and the presence tDVw seems to be related to neonatal mortality. PMID- 27182130 TI - Prevalence and burden of gastrointestinal parasites of Djallonke sheep in Ayeduase, Kumasi, Ghana. AB - AIM: This study was conducted to determine the prevalence and burden of gastrointestinal (GIT) parasites of Djallonke sheep in Ayeduase, Kumasi from January 2015 to July 2015. MATERIALS AND METHODS: The presence of nematodal eggs and coccidial oocysts in fecal samples were analyzed using the saturated sodium chloride floatation technique. Identification of eggs or oocysts was done on the basis of morphology and size of the eggs or oocysts. RESULTS: Out of 110 fecal samples of sheep examined, 108 were infected with GIT parasites, representing a prevalence rate of 98.2%. The total infection rate of GIT nematodes and coccidia oocysts were 94.5% and 51.8%, respectively. Strongyle nematode (94.5%) was the most prevalent GIT nematode detected, followed by strongyloides (27.3%). The average nematodal burden in g/feces was significantly higher (p<0.001) in young rams under 1 year (3482.0) than gimmers (1539.0), lamb (825.0), ewes (420.7), and rams over 1 year (313.3). Nematodal burden in gimmers was significantly higher (p<0.001) than that of lambs, ewes, and rams over 1 year. Nematodal counts of lambs, ewes, and rams did not differ significantly (p>0.05) from each other. The average coccidia oocysts count in g/feces was significantly higher (p<0.001) in lambs (2475.0) than rams under 1 year (286.0), gimmers (263.6), ewes (158.6), and rams over 1 year (150.0). There was no significant difference (p>0.05) in the coccidia oocysts count of rams under 1 year, gimmers, ewes, and rams over 1 year. From the studied animals, 40%, 6.36%, 48.18%, and 5.45% had heavy, moderate, light, and no infestation, respectively, with GIT nematodes. CONCLUSION: Djallonke sheep in Ayeduase, Kumasi, were infested with varying amounts of GIT parasites. The infestation of Djallonke sheep by GIT parasites also varies among different age groups and sexes. PMID- 27182131 TI - Diagnosis and prevalence of ovine pulmonary adenocarcinoma in lung tissues of naturally infected farm sheep. AB - AIM: This study was aimed to detect ovine pulmonary adenocarcinoma (OPA) in sheep flocks affected with pulmonary disorders at organized farm. MATERIALS AND METHODS: A total of 75 sheep died naturally were thoroughly examined for the lesions of OPA during necropsy. Tissue sections from affected portion of the lungs from each animal were collected aseptically and divided into two parts; one each for polymerase chain reaction (PCR) and another for histopathology. RESULTS: On PCR examination of lung tissues, six sheep (8%) were found to be positive for JSRV. Two of them were 3-6 months of age and did not show clinical signs/gross lesions of OPA. Four adult sheep positive on PCR revealed characteristic lesions of OPA on gross and histopathological examination. CONCLUSION: In the absence of known specific antibody response to the infection with JSRV, there is no diagnostic serological test available. The PCR assay employed in this study on lung tissues, using primers based on the U3 region of the viral long terminal repeat for JSRV would be helpful in the screening of preclinical and clinical cases of OPA in sheep. PMID- 27182132 TI - Vertebral scale system to measure heart size in thoracic radiographs of Indian Spitz, Labrador retriever and Mongrel dogs. AB - AIM: To establish reference values of vertebral heart score (VHS) in Indian Spitz, Labrador retriever, and Mongrel dogs; to assess applicability of VHS in these three dog breeds; to determine if breed, recumbency side, gender, body weight, and thoracic depth (TD) to thoracic width (TW) ratio has an influence on the VHS measurement in these dog breeds. MATERIALS AND METHODS: A total of 60, client owned, clinically healthy Indian Spitz (n=20, mean age = 4.25+/-2.15 years, body weight = 11.87+/-2.7 kg), Labrador retriever (n=20, mean age = 4.75+/ 1.91 years, body weight = 27.31+/-5.43 kg), and Mongrel dogs (n=20, mean age = 4.25+/-1.52 years, body weight = 16.25+/-3.99 kg), having no radiological and clinical signs of cardiovascular or pulmonary disease were included in the study. All dogs were restrained manually and left lateral (LL) and right lateral (RL) radiographic views were obtained. The size of heart in lateral radiographs was calculated using VHS method. Besides, the TD, TW and TD: TW were calculated to determine the type of thoracic conformation in the dog breeds. In addition to this, the effect of breed, side of recumbency, gender, body weight, and TD to TW ratio on the calculation of VHS was determined. RESULTS: VHS was calculated in all the animals of the breeds. VHS in Spitz and Labrador retriever was significantly (p<0.0001, p<0.0001, respectively) >9.7+/-0.5 v. RL and LL VHS in Mongrel dog was significantly (p<0.037) >9.7+/-0.5 v. Significant (p<0.05) differences in the VHS were observed among Spitz, Labrador retriever and Mongrel dogs, being higher for Labrador retriever followed by Spitz and Mongrel dogs. VHS in RL recumbency was significantly (p<0.001) greater than VHS in LL recumbency in all three breeds. LL and RL VHS correlated significantly with each other in Spitz (r=0.58; p=0.02), Labrador retriever (r=0.87; p<0.0001), and Mongrel dogs (r=0.93; p<0.0001). Significant (p<0.05) differences in the TD and TW were observed among Spitz, Labrador retriever, and Mongrel dogs. Non-significant effect of gender, body weight, and TD to TW ratio on the VHS measurement was observed in each dog breed. CONCLUSION: Breed-specific VHS reference ranges should be used for the objective measurement of heart size in dogs. Furthermore, the radiographic view should also be taken into consideration to avoid any erroneous interpretation of cardiac enlargement in dogs. PMID- 27182133 TI - Relative efficacy of organic acids and antibiotics as growth promoters in broiler chicken. AB - AIM: The objective of this study was to evaluate the effect of organic acids as replacer to antibiotics in their various combinations on feed consumption, body weight gain, and feed conversion ratio (FCR) in broiler chicks during different phases of growth. MATERIALS AND METHODS: Antibiotics and organic acids were incorporated into boiler feed in different combinations to form 10 maize based test diets (T1 to T10). Each test diet was offered to four replicates of 10 birds each constituting a total of 400 birds kept for 45 days. RESULTS: Significantly better effect in terms of body weight gain from supplementation of 1% citric acid and 1% citric acid along with antibiotic was observed throughout the entire study, whereas the effect of tartaric acid supplementation was similar to control group. Citric acid (1%) along with antibiotic supplementation showed highest feed intake during the experimental period. Significantly better FCR was observed in groups supplemented with 1% citric acid and 1% citric acid along with antibiotic followed by antibiotic along with organic acids supplemented group. CONCLUSION: Growth performance of birds in terms of body weight, body weight gain, and FCR improved significantly in 1% citric acid which was significantly higher than antibiotic supplemented group. 1% citric acid can effectively replace antibiotic growth promoter (chlortetracycline) without affecting growth performance of birds. PMID- 27182134 TI - Detection of Mycobacterium tuberculosis and Mycobacterium bovis in Sahiwal cattle from an organized farm using ante-mortem techniques. AB - AIM: The aim of this study was to investigate the prevalence of bovine tuberculosis (TB) and detection of Mycobacterium bovis in cattle from an organized dairy farm. MATERIALS AND METHODS: A total of 121 animals (93 females and 28 males) of 1 year and above were studied for the prevalence of bovine TB using single intradermal comparative cervical tuberculin (SICCT) test, bovine gamma-interferon (gamma-IFN) enzyme immunoassay, and polymerase chain reactions (PCRs). RESULTS: Out of total 121 animals, 17 (14.04%) animals were positive reactors to SICCT test while only one (0.82%) animal for gamma-IFN assay. By PCR, Mycobacterium TB complex was detected in 19 (15.70%) animals out of which 4 (3.30%) animal were also positive for M. bovis. CONCLUSIONS: Diagnosis of bovine TB can be done in early stage in live animals with multiple approaches like skin test followed by a molecular technique like PCR which showed promising results. PMID- 27182136 TI - Effect of supplemental heat on mortality rate, growth performance, and blood biochemical profiles of Ghungroo piglets in Indian sub-tropical climate. AB - AIM: The present study was conducted to explore the effect of supplemental heat on mortality rate, growth performance, and blood biochemical profiles of indigenous Ghungroo piglets in sub-tropical cold and humid climatic conditions of Tripura, a state of the north eastern hill (NEH) region of India. MATERIALS AND METHODS: The experiment was conducted on 38 indigenous Ghungroo piglets from birth up to 60 days of age. Among the 38 piglets, 19 piglets were provided with supplemental heat ranging between 17.0 degrees C and 21.1 degrees C for the period of the first 30 days and thereafter between 24.1 degrees C and 29.9 degrees C for the next 30 days. The other 19 piglets were exposed to natural environmental minimum temperatures ranging between 7.2 degrees C and 15.0 degrees C during the first 30 days and then between 18.5 degrees C and 25.5 degrees C for the next 30 days. RESULTS: The supplemental heat resulted in 10.6% reduction of piglet mortality from the 2(nd) till the 7(th) day of age. These beneficial effects could be related with the lower (p<0.05) plasma glutamate pyruvate transaminase (GPT) and cortisol levels and higher (p<0.05) plasma alkaline phosphatase (AP) concentrations in heat supplemented group compared to control group. Plasma AP, GPT, glucose, triiodothyronine, and luteinizing hormone concentrations decreased (p<0.05) gradually with the advancement of age in both control and supplemental heat treated piglets. CONCLUSION: Supplemental heat could be beneficial since it is related to a reduction of piglet mortality during the first week of life under farm management system in the sub-tropical climate of NEH region of India. PMID- 27182135 TI - Advances in reproductive biotechnologies. AB - In recent times, reproductive biotechnologies have emerged and started to replace the conventional techniques. It is noteworthy that for sustained livestock productivity, it is imperative to start using these techniques for facing the increasing challenges for productivity, reproduction and health with impending environment conditions. These recent biotechniques, both in male and female, have revolutionized and opened avenues for studying and manipulating the reproductive process both in vitro and in vivo in various livestock species for improving tis efficiency. This review attempts to highlight pros and cons, on the recent developments in reproductive biotechnologies, both in male and female in livestock species. PMID- 27182137 TI - Maggot debridement therapy as primary tool to treat chronic wound of animals. AB - Maggot debridement therapy (MDT) is a safe, effective, and controlled method ofhealing of chronic wounds by debridement and disinfection. In this therapy live, sterile maggots of green bottle fly, Lucilia (Phaenicia) sericata are used, as they prefernecrotic tissues over healthy for feeding. Since centuries, MDT is used in humanbeings to treat chronic wounds. Lately, MDT came out as a potent medical aid in animals. In animals, although, this therapy is still limited and clinical studies are few. However, with the increasing antibiotic resistance and chronic wound infections in veterinary medicine, maggot therapy may even become the first line of treatment for some infections. This paper will present a brief discussion of MDT and its role in veterinary medicine that may add one more treatment method to utilize in non-healing wounds of animals and overcome the use of amputation and euthanasia. The objective of this review paper is to assemble relevant literature on maggot therapy to form a theoretical foundation from which further steps toward clinical use of maggot therapy in animals for chronic wounds can be taken. PMID- 27182138 TI - Conjugation of ampicillin and enrofloxacin residues with bovine serum albumin and raising of polyclonal antibodies against them. AB - AIM: The aim of this study is to test the potency of bovine serum albumin (BSA) conjugated ampicillin (AMP) and enrofloxacin (ENR) antigens in eliciting an immune response in rats using indirect competitive enzyme-linked immunosorbent assay (icELISA). MATERIALS AND METHODS: AMP and ENR antibiotics were conjugated with BSA by carbodiimide reaction using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) as a cross-linker. The successful conjugation was confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Sprague-Dawley rats were immunized with the conjugates and blood samples were collected serially at 15 days time interval after first immunization plus first booster, second booster, third booster, and the fourth sampling was done 11/2 month after the third booster. The antibody titres in the antisera of each antibiotic in all the four immunization cycles (ICs) were determined by an icELISA at various serum dilutions ranging from 1/100 to 1/6400. RESULTS: Analysis of antibiotic-BSA conjugates by sodium dodecyl sulfate polyacrylamide gel electrophoresis and coomassie blue staining revealed high molecular weight bands of 85 kDa and 74 kDa for AMP-BSA and ENR-BSA respectively when compared to 68 kDa band of BSA. Both the antibiotic conjugates elicited a good immune response in rats but comparatively the response was more with AMP-BSA conjugate than ENR-BSA conjugate. Maximum optical density 450 value of 2.577 was recorded for AMP-BSA antisera, and 1.723 was recorded for ENR-BSA antisera at 1/100(th) antiserum dilution in third IC. CONCLUSION: AMP and ENR antibiotics proved to be good immunogens when conjugated to BSA by carbodiimide reaction with EDC as crosslinker. The polyclonal antibodies produced can be employed for detecting AMP and ENR residues in milk and urine samples. PMID- 27182139 TI - In vitro larvicidal effects of ethanolic extract of Curcuma longa Linn. on Haemonchus larval stage. AB - AIM: Gastrointestinal helminthosis is a global problem in small ruminant production. Most parasites have developed resistance to commonly available anthelminthic compounds, and there is currently an increasing need for new compounds with more efficacies. This study evaluated the in vitro effects of ethanolic extract of Curcuma longa (EECL) as a biological nematicide against third stage Haemonchus larvae (L3) isolated from sheep. MATERIALS AND METHODS: Haemonchus L3 were cultured and harvested from the feces of naturally infected sheep. EECL was prepared and three concentrations; 50, 100, and 200 mg/mL were tested for their efficacies on Haemonchus L3. Levamisole at concentration 1.5 and 3 mg/mL were used as positive controls. RESULTS: EECL showed anthelmintic activity in a dose-dependent manner with 78% worm mortality within 24 h of exposure at the highest dose rate of 200 mg/mL. There was a 100% worm mortality rate after 2 h of levamisole (3 mg/mL) admisntration. However, there was a comparable larvicidal effect between when levamisole (1.5 mg/mL) and EECL (200 mg) were administered. CONCLUSION: The study shows that EECL does exhibit good anthelmintic properties at 200 mg/mL which is comparable with levamisole at 1.5 mg/mL. PMID- 27182140 TI - Polymorphism in spa gene of Staphylococcus aureus from bovine subclinical mastitis. AB - AIM: The virulence-associated protein-A of Staphylococcus aureus, encoded by spa gene shows a variation in length in different strains. In this study, the spa gene variation in S. aureus strains was studied which were isolated from subclinical cases of bovine mastitis. MATERIALS AND METHODS: About 38 isolatesof S. aureus were recovered from Holstein-Friesian (HF) crossbred (n=16) and Rathi cattle (n=22) with subclinical mastitis as per standard procedures, and these isolates were subjected to amplification of spa gene (X-region) by polymerase chain reaction and calculation of number of tandem repeats were done. RESULTS: Of the 16 isolates from H-F crossbred cattle, all with the exception of one isolate produced spa amplicon. Seven isolates produced amplicons of 200 bp, one produced 160 bp, and other seven produced spa amplicon of 150 bp with calculated number of 6, 5, and 4 repeats, respectively, whereas nine different types of amplicons were produced by 22 S. aureus isolates from Rathi cattle, viz., 280, 250, 240, 200, 190, 180, 170, 150, and 140 bp with 10, 8, 8, 6, 6, 6, 5, 4, and 4 repeats, respectively. One of the isolates from Rathi cattle produced two spa amplicons (150 and 190 bp). CONCLUSION: A greater polymorphism was observed in the S. aureus isolates from Rathi cattle than from H-F crossbreds with subclinical mastitis. PMID- 27182141 TI - Comparative study on immunoglobulin Y transfer from breeding hens to egg yolk and progeny chicks in different breeds of poultry. AB - AIM: This study was undertaken to compare the immunoglobulin Y (IgY) level and its efficacy in laying hens of four different breeds of poultry (viz., Vanraja, Gramapriya, BlackRock, and KalingaBrown) and its relative transfer in egg yolk and chick. MATERIALS AND METHODS: This study was conducted in 48 apparently healthy laying hens vaccinated with Salmonella inactivated polyvalent vaccine, eggs and progeny chicks; 12 each from four different breeds of poultry, viz., Vanraja, Gramapriya, BlackRock, and KalingaBrown. The methodology included measurement of egg and yolk weight, total protein and IgY in egg yolk, total serum protein and IgY in breeding hens, and progeny chicks and extent of IgY transfer from hens to yolk then to chicks. Further, Salmonella-specific antibodies in breeding hens, egg yolk and progeny chicks were assessed using O and H antigen by tube agglutination test. RESULTS: The egg weight differed nonsignificantly (p>0.05) among breeds, however, breed wise significant variation (p<0.01) was reported in yolk weight. The weight of egg yolk significantly affects the total protein and IgY concentration although these levels per unit of volume did not differ. Total protein was significantly higher (p<0.01) in KalingaBrown and Gramapriya as compared to Vanraja and BlackRock. Non-significant (p>0.05) difference among breed was found in total protein of egg yolk and chick. The IgY concentration in hens, egg yolk and chick was found to be in the range of 5.35+/-0.63-5.83+/-0.65, 2.3+/-0.1-2.6+/-0.2, and 1.3+/-0.11-1.7+/-0.16 mg/ml, respectively which is uniform and independent of total protein concentration at all the three levels. Significant breed variations were not observed in maternal IgY transfer from breeding hens to chicks and were 25.62+/-1.42-36.06+/-4.34% of total IgY in parent flock. Moderate to higher rate of seroprevalence with peak titers of 1:640 against Salmonella-specific antibodies was observed in only 41.6% of breeding hens. CONCLUSION: No significant difference in the rate of transfer of IgY was observed in four breeds studied (viz., Vanraja, Gramapriya, BlackRock, and KalingaBrown) and moderate seropositivity was detected for Salmonella specific antibodies in progeny chicks. PMID- 27182142 TI - Surgical approaches for total knee arthroplasty. AB - There are various surgical approaches to the knee joint and its surrounding structures and such approaches are generally designed to allow the best access to an area of pathology whilst safeguarding important surrounding structures. Controversy currently surrounds the optimal surgical approach for total knee arthroplasty (TKA). The medial parapatellar arthrotomy, or anteromedial approach, has been the most used and has been regarded as the standard approach for exposure of the knee joint. It provides extensive exposure and is useful for open anterior cruciate ligament reconstruction, total knee replacement, and fixation of intra-articular fractures. Because this approach has been implicated in compromise of the patellar circulation, some authors have advocated the subvastus, midvastus, and trivector approaches for exposure of the knee joint. While these approaches expose the knee from the medial side, the anterolateral approach exposes the knee joint from the lateral side. With careful planning and arthrotomy selection, the anterior aspect of the joint can be adequately exposed for TKA in different clinical scenarios. PMID- 27182143 TI - Increased risk of adverse events in management of femur and tibial shaft fractures with plating: An analysis of NSQIP data. AB - BACKGROUND: The management of femoral and tibial shaft fractures has long been among the simplest in orthopaedic trauma. Little data exist on the predictors of complications associated with these fractures. The evolving healthcare system is creating a focus on quality metrics and changing payment models. It is critical that traumatologists develop a better understanding of complication rates associated with these injuries so that they may continue to improve patient care while also reducing overall medical costs. METHODS: Using the ACS-NSQIP database, we evaluated patient demographics, comorbidities and 30-day complications of femoral and tibial fractures. A bivariate analysis was then used to compare rates of minor and major post-operative complications within 30 days. A multivariate logistic regression was performed, assessing the odds of developing a minor and/or major complication up to 30 days post-surgery. RESULTS: 2891 patients were identified. For femoral fractures, intramedullary nailing (IMN) demonstrated an overall complication rate of 14.9% (n = 151) whereas open reduction and internal fixation (ORIF) with plating showed an overall complication rate of 15.6% (n = 70). Patients undergoing plating of the femur or tibia were 2 times more likely than the IMN patients to demonstrate postoperative complications. CONCLUSION: Our study is the first to demonstrate that plating of femoral and tibial fractures doubles the odds of developing a complication. As our healthcare system shifts to bundled payment plans, it is impertinent for the orthopaedic surgeon to understand the risk factors associated with fracture treatments in order to assess the best treatment plan. PMID- 27182144 TI - Prevalence of skeletal deformity due to nutritional rickets in children between 1 and 18 years in tea garden community. AB - INTRODUCTION: The present study was undertaken to find out the prevalence of skeletal deformity due to nutritional rickets in children aged 1-18 years in tea garden community in Dibrugarh District of Assam. METHODOLOGY: It was a cross sectional study and two-stage cluster sampling was used. In the selected tea gardens, all the children aged 1-18 years were screened for skeletal deformity by house-to-house visit. RESULTS AND OBSERVATIONS: The overall prevalence of skeletal deformity was 2.7 per thousand. Majority of children with deformities (57.27%) were between 7 and 12 years of age. Widening of wrists and ankle was the most frequent symptom (53.8%). Most of the children with deformity had moderate malnutrition (77.27%). Most of the children with skeletal deformity belong to lower (v) (45.45%) grade of Kuppuswamy's grading scale. Bilateral genu valgus deformity (54.54%) and bilateral genu varum (25.92%) deformity were the most common deformities. Widening of wrists and ankle was the most frequent symptom (61.66%). CONCLUSION: Of the 16,274 tea garden children included in our study (male and female) in the age group 1-18 years, 44 had skeletal deformity due to nutritional rickets. The prevalence of skeletal deformity due to nutritional rickets was found to be 2.7 per thousand children, which are significantly higher when compared with the only other such study, which was on general population in Bangladesh. PMID- 27182146 TI - Validation of thoracic injury rule out criteria as a decision instrument for screening of chest radiography in blunt thoracic trauma. AB - BACKGROUND: Thoracic injury rule out criteria (TIRC) were first introduced as a decision instrument for selective chest radiography in blunt thoracic trauma in 2014. However, the validity of this model has not been assessed in other studies. In this regard, the present survey evaluates the validity of TIRC model in a multi-center setting. METHODS: In this cross-sectional study, clinical presentations and chest radiograms of multiple trauma patients referring to 6 educational hospitals in Iran were evaluated. Data were gathered prospectively during 2015. In each center, data collection and interpretation of radiograms were conducted by two different emergency medicine specialists. Measures were then taken for assessment of discriminatory power and calibration of the model. RESULTS: Data from 2905 patients were gathered (73.17% were male; the mean age was 33.53 +/- 15.42 years). Area under the receiver operating characteristics curve of the TIRC model for detection of thoracic traumatic injuries was 0.93 (95%CI: 0.93-0.94). Sensitivity and specificity of the model were 100 (98.91-100) and 67.65 (65.76-69.45), respectively. The intercept of TIRC calibration plot was 0.08 (95%CI: 0.07-0.09), and its slope was 1.19 (95%CI: 1.15-1.24), which are indicative of the model being perfect in detecting presence or absence of lesions in chest radiograms. CONCLUSION: The findings are corroborative of external validation, good discrimination, and proper calibration of TIRC model in screening of multiple trauma patients for obtaining chest radiograms. PMID- 27182145 TI - The effect of vitamin D and bisphosphonate on fracture healing: An experimental study. AB - BACKGROUND: The aim of the study was to evaluate the effects of the using bisphosphonate, vitamin D, and a combination of bisphosphonate and vitamin D on fracture healing, by comparison of radiological and histological findings of the study groups and a control group. METHODS: A total of 24 rats were randomly divided into 4 groups. A mid-third fracture was created in the femur of all rats. Saline was administered to Group A, bisphosphonate (Alendronate) to Group B, bisphosphonate (Alendronate) + vitamin D (Calcitriol) to Group C and vitamin D (Calcitriol) to Group D. All preparations were administered orally for 28 days. RESULTS: No statistically significant difference was determined between the groups in respect of the effect on fracture healing according to radiological findings. The histological findings of fracture healing showed Groups B and C to be significantly more advanced than Group A (p = 0.017, p = 0.009). However no significant difference was found in Group D comparison with Group A (p = 0.224). CONCLUSION: According to the histological findings, advanced fracture healing was seen in the groups administered with bisphosphonate or combined bisphosphonate and vitamin D compared to the use of vitamin D alone and the control group. It was concluded that bisphosphonate treatment combined with vitamin D can be used safely without any negative effect on fracture healing. PMID- 27182147 TI - Computed tomographic-based morphometric study of thoracic spine and its relevance to anaesthetic and spinal surgical procedures. AB - BACKGROUND: To collect a baseline computer software aided normative morphometric data of thoracic spine in the Indian population and analyze it to give pre procedural guidelines to clinicians for safe surgical and anaesthetic procedures in the thoracic spine. METHODS: CT scans of thoracic spine of patients free from spinal disorders were reviewed in a total of 600 vertebrae in 50 patients. Parameters recorded with the help of computer software were pedicle width, length and height, transverse pedicle angles, chord length, canal dimensions, body width and height, spinous process angle and transverse process length. RESULTS: Pedicle width decreased from T1 (9.27 +/- 1.01) to T4 (4.5 +/- 0.93) and increased to T12 (8.31 +/- 1.83). At T4 76% and at T5 62% of the pedicles were smaller than 5 mm and would not accept 4 mm screw with 1.0-mm clearance. However, at T1 2%, at T11 7% and at T12 8% would not accept a 4 mm screw. Chord length gradually increased in upper thoracic vertebrae and was relatively constant in middle and decreased in lower thoracic vertebrae. Shortest estimated chord length was at T1 (30.30 +/- 2.11). On an average, from T1 to T6 and at T11 and T12, a screw length of 25-30 mm could be accommodated and from T7 to T10, 30-35 mm screw length could be accommodated. Transverse pedicle angle decreased from T1 (35.4 +/- 2.21) to T12 ( 9.8 +/- 2.39). Canal dimensions were narrowest at T4/T5 (20.02 +/- 1.23) in anteroposterior and 21.12 +/- 1.23 in interpedicular diameters. Spinous process angle increased from T1 (30.11 +/- 6.74) to T6 (57.89 +/- 9.31) and decreased to 16.21 +/- 7.38 at T12. Transverse process length increased from T1 to T7 (23.54 + 2.12 to 31.21 + 1.91) and then decreased to 12.11 + 2.3 at T12. Vertebral body dimensions showed increasing trends from T1 to T12. CONCLUSIONS: A thorough knowledge of anatomical and radiological characteristics of the spine and their variations is essential for the clinicians. Data collected in the present study provides baseline normative values in Indian population and will help in guiding safe and effective completion of both surgical and anaesthetic procedures in the thoracic spine. Computer software aided morphometric data can help in selecting appropriate size and optimal placement of the implant with minimal procedural difficulties and complications during spine surgery. PMID- 27182148 TI - Histopathological, immunohistochemical, and image analytic parameters characterizing the stromal component in primary and recurrent giant cell tumor of bone. AB - Giant cell tumor (GCT) of bone is a benign locally aggressive tumor whose biological behavior is unpredictable. Currently, there are no definitive clinical, histological, biochemical, or immunological parameters that can predict its behavior. This study was undertaken to examine whether delineation of reactive and neoplastic stromal component of GCT can help in this regard. 55 cases of GCT (30 primary, 25 recurrent) were subjected to histopathological grading, immunohistochemistry, and image analysis. Spindling of stroma was more frequent in recurrent GCT with 64% cases having more than 50% spindled stroma (p < 0.001). Number of mitosis/10 HPF and higher grade were more in recurrent GCT. Mean percentage positivity for CD68 (38.36%) and alpha1-ACT (70.86%) was higher in primary than recurrent GCT. PCNA and MiB-1 labeling indices were higher in recurrent (42.62% and 9.18%, respectively) than in primary group (24.75% and 7.7%, respectively). A single numerical parameter encompassing stromal cell population and its proliferation was derived as ratio of PCNA/CD68 and PCNA/alpha1-ACT. Both ratios were higher in recurrent (0.81 +/- 0.38; 1.58 +/- 1.50) than in primary GCT (0.58 +/- 0.62; 0.34 +/- 0.29) (p = 0.002; 0.01). On image analysis, parameters significantly different between the two groups were nuclear area and nuclear integrated optical density. It was thus concluded that recurrent GCT shows higher grade, increased mitosis, more spindling, fewer reactive components, and higher proliferation than primary GCT. Delineation of reactive component (alpha1-ACT positive) and proliferating component (PCNA positive cells) using immunohistochemistry with calculation of the PCNA/ACT ratio delivers more information than image analysis. PMID- 27182149 TI - Ipsilateral hip and knee dislocation: Case report and review of literature. AB - Hip and knee dislocations are not uncommon but simultaneous ipsilateral dislocation of the hip and knee joint is rare; consequently, there is an inadequate amount of literature on the subject. We identified only 11 such cases reported in English literature. In the present report, we describe the case of a 23-year-old male patient who presented with ipsilateral hip and knee dislocation on the right side after being involved in a road traffic accident. The hip dislocation was associated with a posterior wall acetabular fracture. The hip as well as the knee joints was reduced in the emergency bay. The patient underwent an urgent fixation of the posterior wall acetabular fracture with delayed ligament reconstruction for the knee dislocation. At one-year follow-up, he had no pain in the hip or knee. There was grade 1 posterior sag but no symptoms of knee instability. Radiographs revealed no evidence of avascular necrosis or arthritis of the femoral head. The normal treatment protocol for individual injury is affected by the simultaneous occurrence of hip and knee dislocation. PMID- 27182150 TI - Cerebrotendinous xanthomatosis; a genetic condition: Clinical profile of three patients from a rural Indian family and review of literature. AB - INTRODUCTION: Cerebrotendinous xanthomatosis is a rare lipid storage disease characterized by infantile onset diarrhea, cataract, tendon xanthomas, and progressive neurologic dysfunction. Cerebrotendinous xanthomatosis is exceptionally rare in Indian population with only few case reports till now. CASE REPORT: An 18-year-old male presented to orthopedic outpatients clinic with complaints of insidious onset swelling of both achilles over last 3 years, with history of learning and visual difficulties. On examination, there were firm nontender swellings along the course of both tendoachillis. Plantar response was extensor and Romberg test was positive with eyes closed. Cranial MRI showed diffuse cerebral and cerebellar atrophy. Family history showed history of diarrhea, mental retardation, and visual difficulties in his two younger siblings. They were also called upon and evaluated clinically. All three were diagnosed as having cerebrotendinous xanthomatosis based on clinical and radiological features. CONCLUSION: Cerebrotendinous xanthomatosis is a progressive and preventable disorder and it benefits from therapy, so early diagnosis is mandatory to prevent significant morbidity and mortality associated with this disease. PMID- 27182151 TI - Microfilarial involvement of the neck region: A case report and review of literature. AB - INTRODUCTION: Filariasis is caused by parasitic infections, most commonly Brugia malayi and Wuchereria bancrofti. India is one of the endemic countries for such disease. The usually involved organs are lower limbs and external genitalia. Neck region is rarely involved and only a few cases have been reported in literature. CASE REPORT: We reported such a case where filarial involvement has involved the neck region and reached up to the level of upper cervical vertebra. A huge neck swelling and torticollis were the main presenting features. Diagnosis was confirmed by MRI and live presence of microfilarial parasite in FNAC. The patient responded excellently to antihelminthic drugs. He has been under our regular follow-up and there has been no complication till date. DISCUSSION: The purpose of this case report was to highlight this rare presentation of microfilaria parasite. PMID- 27182152 TI - Forgotten intrauterine contraceptive device - A threat to total hip prosthesis: A case report with review of the literature. AB - Primary total hip replacement has become a routine procedure these days. With improvement in surgical techniques and implant designs, the survival rate of prosthesis has increased significantly but unfortunately, prosthetic infections though uncommon continue to be a threatening complication. We present a detailed review of the literature along with a case report of infected total hip prosthesis in a 36-year-old female who had been operated 6 years back. The causative organism was found to be Actinomyces israelii which was related to an infected intrauterine device used for contraception that had been forgotten after being implanted 8 years earlier. PMID- 27182153 TI - Comment on "Evaluation of proximal femoral locking plate in unstable extracapsular proximal femoral fractures: Surgical technique & mid term follow up results" [J. Clin. Orthop. Trauma 5 (3) (2014) 137-145]. PMID- 27182155 TI - Liver transplantation: Current status and challenges. AB - Great progress has been made in the field of liver transplantation over the past two decades. This progress, however, also brings up the next set of challenges: First, organ shortage remains a major limitation, and accounts for a large proportion of wait list mortality. While living donation has successfully increased the total number of liver transplants done in Asian countries, the total number of such transplants has been stagnant in the western hemisphere. As such, there has been a significant effort over the past decade to increase the existing deceased donor pool. This effort has resulted in a greater use of liver allografts following donation after cardiac death (DCD) along with marginal and extended criteria donors. Improved understanding of the pathophysiology of liver allografts procured after circulatory arrest has not only resulted in better selection and management of DCD donors, but has also helped in the development of mechanical perfusion strategies. Early outcomes demonstrating the clinical applicability of both hypothermic and normothermic perfusion and its potential to impact patient survival and allograft function have generated much interest. Second, long-term outcomes of liver transplant recipients have not improved significantly, as recipients continue to succumb to complications of long-term immunosuppression, such as infection, malignancy and renal failure. Furthermore, recent evidence suggests that chronic immune-mediated injury to the liver may also impact graft function. PMID- 27182154 TI - Thrombin activation and liver inflammation in advanced hepatitis C virus infection. AB - Hepatitis C virus (HCV) infection is associated with increased thrombotic risk. Several mechanisms are involved including direct endothelial damage by the HCV virus, with activation of tissue factor, altered fibrinolysis and increased platelet aggregation and activation. In advanced stages, chronic HCV infection may evolve to liver cirrhosis, a condition in which alterations in the portal microcirculation may also ultimately lead to thrombin activation, platelet aggregation, and clot formation. Therefore in advanced HCV liver disease there is an increased prevalence of thrombotic phenomena in portal vein radicles. Increased thrombin formation may activate hepatic stellate cells and promote liver fibrosis. In addition, ischemic changes derived from vascular occlusion by microthrombi favor the so called parenchymal extinction, a process that promotes collapse of hepatocytes and the formation of gross fibrous tracts. These reasons may explain why advanced HCV infection may evolve more rapidly to end-stage liver disease than other forms of cirrhosis. PMID- 27182157 TI - Combined hepatocellular cholangiocarcinoma: Controversies to be addressed. AB - Combined hepatocellular cholangiocarcinoma (CHC) accounts for 0.4%-14.2% of primary liver cancer cases and possesses pathological features of both hepatocellular carcinoma and cholangiocarcinoma. Since this disease was first described and classified in 1949, the classification of CHC has continuously evolved. The latest definition and classification of CHC by the World Health Organization is based on the speculation that CHC arises from hepatic progenitor cells. However, there is no evidence demonstrating the common origin of different components of CHC. Furthermore, the definition of CHC subtypes is still ambiguous and the identification of CHC subtype when a single tumor contains many components has remained unresolved. In addition, there is no summary on the newly recognized histopathology features or the contribution of CHC components to prognosis and outcome of this disease. Here we provide a review of the current literature to address these questions. PMID- 27182159 TI - Role of estrogen receptor beta selective agonist in ameliorating portal hypertension in rats with CCl4-induced liver cirrhosis. AB - AIM: To investigate the role of diarylpropionitrile (DPN), a selective agonist of estrogen receptor beta (ERbeta), in liver cirrhosis with portal hypertension (PHT) and isolated hepatic stellate cells (HSCs). METHODS: Female Sprague-Dawley rats were ovariectomized (OVX), and liver cirrhosis with PHT was induced by CCl4 injection. DPN and PHTPP, the selective ERbeta agonist and antagonist, were used as drug interventions. Liver fibrosis was assessed by hematoxylin and eosin (HE) and Masson's trichrome staining and by analyzing smooth muscle actin expression. Hemodynamic parameters were determined in vivo using colored microspheres technique. Protein expression and phosphorylation were determined by immunohistochemical staining and Western blot analysis. Messenger RNA levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Collagen gel contraction assay was performed using gel lattices containing HSCs treated with DPN, PHTPP, or Y-27632 prior to ET-1 addition. RESULTS: Treatment with DPN in vivo greatly lowered portal pressure and improved hemodynamic parameters without affecting mean arterial pressure, which was associated with the attenuation of liver fibrosis and intrahepatic vascular resistance (IHVR). In CCl4-treated rat livers, DPN significantly decreased the expression of RhoA and ROCK II, and even suppressed ROCK II activity. Moreover, DPN remarkedly increased the levels of endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS, and promoted the activities of protein kinase G (PKG), which is an NO effector in the liver. Furthermore, DPN reduced the contractility of activated HSCs in the 3 dimensional stress-relaxed collagen lattices, and decreased the ROCK II activity in activated HSCs. Finally, in vivo/in vitro experiments demonstrated that MLC activity was inhibited by DPN. CONCLUSION: For OVX rats with liver cirrhosis, DPN suppressed liver RhoA/ROCK signal, facilitated NO/PKG pathways, and decreased IHVR, giving rise to reduced portal pressure. Therefore, DPN represents a relevant treatment choice against PHT in cirrhotic patients, especially postmenopausal women. PMID- 27182156 TI - Advances in inducing adaptive immunity using cell-based cancer vaccines: Clinical applications in pancreatic cancer. AB - The incidence of pancreatic ductal adenocarcinoma (PDA) is on the rise, and the prognosis is extremely poor because PDA is highly aggressive and notoriously difficult to treat. Although gemcitabine- or 5-fluorouracil-based chemotherapy is typically offered as a standard of care, most patients do not survive longer than 1 year. Therefore, the development of alternative therapeutic approaches for patients with PDA is imperative. As PDA cells express numerous tumor-associated antigens that are suitable vaccine targets, one promising treatment approach is cancer vaccines. During the last few decades, cell-based cancer vaccines have offered encouraging results in preclinical studies. Cell-based cancer vaccines are mainly generated by presenting whole tumor cells or dendritic cells to cells of the immune system. In particular, several clinical trials have explored cell based cancer vaccines as a promising therapeutic approach for patients with PDA. Moreover, chemotherapy and cancer vaccines can synergize to result in increased efficacies in patients with PDA. In this review, we will discuss both the effect of cell-based cancer vaccines and advances in terms of future strategies of cancer vaccines for the treatment of PDA patients. PMID- 27182158 TI - Epithelial-to-mesenchymal transition in pancreatic ductal adenocarcinoma: Characterization in a 3D-cell culture model. AB - AIM: To analyze the effect of three-dimensional (3D)-arrangement on the expression of epithelial-to-mesenchymal transition markers in pancreatic adenocarcinoma (PDAC) cells. METHODS: HPAF-II, HPAC, and PL45 PDAC cells were cultured in either 2D-monolayers or 3D-spheroids. Ultrastructure was analyzed by transmission electron microscopy. The expression of E-cadherin, beta-catenin, N cadherin, collagen type I (COL-I), vimentin, alpha-smooth muscle actin (alphaSMA), and podoplanin was assayed by confocal microscopy in cells cultured on 12-mm diameter round coverslips and in 3D-spheroids. Gene expression for E cadherin, Snail, Slug, Twist, Zeb1, and Zeb2 was quantified by real-time PCR. E cadherin protein level and its electrophoretic pattern were studied by Western blot in cell lysates obtained from cells grown in 2D-monolayers and 3D-spheroids. RESULTS: The E-cadherin/beta-catenin complex was expressed in a similar way in plasma membrane cell boundaries in both 2D-monolayers and 3D-spheroids. E cadherin increased in lysates obtained from 3D-spheroids, while cleavage fragments were more evident in 2D-monolayers. N-cadherin expression was observed in very few PDAC cells grown in 2D-monolayers, but was more evident in 3D spheroids. Some cells expressing COL-I were observed in 3D-spheroids. Podoplanin, expressed in collectively migrating cells, and alphaSMA were similarly expressed in both experimental conditions. The concomitant maintenance of the E cadherin/beta-catenin complex at cell boundaries supports the hypothesis of a collective migration for these cells, which is consistent with podoplanin expression. CONCLUSION: We show that a 3D-cell culture model could provide deeper insight into understanding the biology of PDAC and allow for the detection of marked differences in the phenotype of PDAC cells grown in 3D-spheroids. PMID- 27182160 TI - miR-30b inhibits autophagy to alleviate hepatic ischemia-reperfusion injury via decreasing the Atg12-Atg5 conjugate. AB - AIM: To explore the role and potential mechanism of miR-30b regulation of autophagy in hepatic ischemia-reperfusion injury (IRI). METHODS: An animal model of hepatic IRI was generated in C57BL/6 mice. For in vitro studies, AML12 cells were immersed in mineral oil for 1 h and then cultured in complete Dulbecco's Modified Eagle's Medium (DMEM)/F12 to simulate IRI. Mice and cells were transfected with miR-30b agomir/mimics or antagomir/inhibitor to examine the effect of miR-30b on autophagy to promote hepatic IRI. The expression of miR-30b was measured by real-time polymerase chain reaction. Apoptotic cells were detected by terminal uridine nick-end labeling (TUNEL) staining, and cell viability was detected by methylthiazole tetrazolium assay. The expression of light chain 3, autophagy-related gene (Atg)12, Atg5, P62, and caspase-3 were detected by western blotting analysis. RESULTS: miR-30b levels were significantly downregulated after hepatic IRI, and the numbers of autophagosomes were increased in response to IRI both in vivo and in vitro. These findings demonstrate that low levels of miR-30b could promote hepatic IRI. Furthermore, we found that miR-30b interacted with Atg12-Atg5 conjugate by binding to Atg12. Overexpression of miR 30b diminished Atg12 and Atg12-Atg5 conjugate levels, which promoted autophagy in response to IR. In contrast, downregulation of miR-30b was associated with increased Atg12-Atg5 conjugate levels and increased autophagy. CONCLUSION: miR 30b inhibited autophagy to alleviate hepatic ischemia-reperfusion injury via decreasing the Atg12-Atg5 conjugate. PMID- 27182162 TI - Elevated serum interleukin-38 level at baseline predicts virological response in telbivudine-treated patients with chronic hepatitis B. AB - AIM: To investigate serum interleukin (IL)-38 level and its clinical role in predicting virological response (VR) to telbivudine (LdT) in patients with chronic hepatitis B (CHB). METHODS: The study participants were divided into two groups; one group consisted of 43 healthy controls (HCs) and the other group consisted of 46 patients with hepatitis B e antigen-positive CHB. All patients were administered 600 mg of oral LdT daily for 52 wk, and they visited physicians every 12 wk for physical examination and laboratory tests. Serum IL-38 levels were determined using ELISA. The concentrations of serum Th1- and Th2-type cytokines were measured using the cytometric bead array (CBA) method. RESULTS: Serum levels of IL-38 at baseline in all patients were higher than those in HCs [306.97 (123.26-492.79) pg/mL vs 184.50 (135.56-292.16) pg/mL, P = 0.019]; the levels returned to normal after the first 12 wk of treatment with LdT [175.51 (103.90-331.91) pg/mL vs 184.50 (135.56-292.16) pg/mL, P > 0.05]. Serum IL-38 levels at baseline were positively associated with serum aspartate aminotransferase levels in patients with CHB (r = 0.311, P = 0.036). Higher levels of serum IL-38 at baseline were associated with a greater probability of VR to LdT treatment at 24 wk (48.15% vs 15.79%, P = 0.023) and 52 wk (66.67% vs 36.84%, P = 0.044). The levels of serum IL-38 in patients with primary non response at week 12 after treatment initiation were lower than those in patients with primary response [64.44 (49.85-172.08) pg/mL vs 190.54 (121.35-355.28) pg/mL, P = 0.036]. Serum IL-38 levels were correlated with serum IL-6 and IL-12 levels in patients with CHB during treatment with LdT. CONCLUSION: Elevated serum IL-38 levels in untreated CHB patients reflect ongoing liver injury. Higher serum IL-38 levels before treatment indicate a greater probability of VR to LdT treatment. PMID- 27182161 TI - Dissecting characteristics and dynamics of differentially expressed proteins during multistage carcinogenesis of human colorectal cancer. AB - AIM: To discover novel biomarkers for early diagnosis, prognosis or treatment of human colorectal cancer. METHODS: iTRAQ 2D LC-MS/MS analysis was used to identify differentially expressed proteins (DEPs) in the human colonic epithelial carcinogenic process using laser capture microdissection-purified colonic epithelial cells from normal colon, adenoma, carcinoma in situ and invasive carcinoma tissues. RESULTS: A total of 326 DEPs were identified, and four DEPs (DMBT1, S100A9, Galectin-10, and S100A8) with progressive alteration in the carcinogenic process were further validated by immunohistochemistry. The DEPs were involved in multiple biological processes including cell cycle, cell adhesion, translation, mRNA processing, and protein synthesis. Some of the DEPs involved in cellular process such as "translation" and "mRNA splicing" were progressively up-regulated, while some DEPs involved in other processes such as "metabolism" and "cell response to stress" was progressively down-regulated. Other proteins with up- or down-regulation at certain stages of carcinogenesis may play various roles at different stages of the colorectal carcinogenic process. CONCLUSION: These findings give insights into our understanding of the mechanisms of colorectal carcinogenesis and provide clues for further investigation of carcinogenesis and identification of biomarkers. PMID- 27182163 TI - Expression of B7-H4 and hepatitis B virus X in hepatitis B virus-related hepatocellular carcinoma. AB - AIM: To investigate the expression and clinical significance of B7-H4 and hepatitis B virus X (HBx) protein in hepatitis B virus-related hepatocellular carcinoma (HBV-HCC). METHODS: The expression of B7-H4 in the human HCC cell lines HepG2 and HepG2.2.15 were detected by western blot, flow cytometry, and immunofluorescence. The expression of B7-H4 and HBx in 83 HBV-HCC was detected by immunohistochemistry, and the relationship with clinicopathological features was analyzed. Paraffin sections were generated from 83 HBV-HCC patients (22 females and 61 males) enrolled in this study. The age of these patients ranged from 35 to 77 years, with an average of 52.5 +/- 11.3 years. All experiments were approved by the Ethics Committees of the Second Affiliated Hospital, Zhejiang University School of Medicine. RESULTS: B7-H4 was significantly upregulated in HepG2.2.15 cells compared to HepG2 cells. Specifically, the protein expression of B7-H4 in the lysates of HepG2 cells was more than that in HepG2.2.15 cells. In addition, HBx was expressed only in HepG2.2.15 cells. Similar data were obtained by flow cytometry. The positive rates of B7-H4 and HBx in the tissues of 83 HBV-HCC patients were 68.67% (57/83) and 59.04% (49/83), respectively. The expression of HBx was correlated with tumor node metastases (TNM) stage, and the expression of B7-H4 was positively correlated with HBx (rs = 0.388; P < 0.01). The expression level of B7-H4 in HBx-positive HBV-HCC tissues was substantially higher than that in HBx-negative HBV-HCC tissues. The expression level of B7H4 was negatively related to tumor TNM stage. CONCLUSION: Higher expression of HBx and B7-H4 was correlated with tumor progression of HBV-HCC, suggesting that B7-H4 may be involved in facilitating HBV-related hepatocarcinogenesis. PMID- 27182165 TI - Video capsule endoscopy in left ventricular assist device recipients with obscure gastrointestinal bleeding. AB - AIM: To assess whether video capsule endoscopy (VCE) affects the outcomes of left ventricular assist devices (LVADs) recipients with gastrointestinal bleeding. METHODS: This is a retrospective study of LVAD recipients with obscure gastrointestinal bleeding (OGIB) who underwent VCE at a tertiary medical center between 2005 and 2013. All patients were admitted and monitored with telemetry and all VCE and subsequent endoscopic procedures were performed as inpatients. A VCE study was considered positive only when P2 lesions were found and was regarded as negative if P1 or P0 were identified. All patients were followed until heart transplant, death, or the end of the study. RESULTS: Between 2005 and 2013, 30 patients with LVAD underwent VCE. Completion rate of VCE was 93.3% and there was no capsule retention. No interference of VCE recording or the function of LVAD was found. VCE was positive in 40% of patients (n = 12). The most common finding was active small intestinal bleeding (50%) and small intestinal angiodysplasia (33.3%). There was no difference in the rate of recurrent bleeding between patients with positive and negative VCE study (50.0% vs 55.6%, P = 1.00) during an average of 11.6 +/- 9.6 mo follow up. Among patients with positive VCE, the recurrent bleeding rate did not differ whether subsequent endoscopy was performed (50% vs 50%, P = 1.00). CONCLUSION: VCE can be safely performed in LVAD recipients with a diagnostic yield of 40%. VCE does not affect recurrent bleeding in LVAD patients regardless of findings. PMID- 27182164 TI - Predictive factors for survival and score application in liver retransplantation for hepatitis C recurrence. AB - AIM: To identify risk factors associated with survival in patients retransplanted for hepatitis C virus (HCV) recurrence and to apply a survival score to this population. METHODS: We retrospectively identified 108 patients retransplanted for HCV recurrence in eight European liver transplantation centers (seven in France, one in Spain). Data collection comprised clinical and laboratory variables, including virological and antiviral treatment data. We then analyzed the factors associated with survival in this population. A recently published score that predicts survival in retransplantation in patients with hepatitis C was applied. Because there are currently no uniform recommendations regarding selection of the best candidates for retransplantation in this setting, we also described the clinical characteristics of 164 patients not retransplanted, with F3, F4, or fibrosing cholestatic hepatitis (FCH) post-first graft presenting with hepatic decompensation. RESULTS: Overall retransplantation patient survival rates were 55%, 47%, and 43% at 3, 5, and 10 years, respectively. Patients who were retransplanted for advanced cirrhosis had survival rates of 59%, 52%, and 49% at 3, 5, and 10 years, while those retransplanted for FCH had survival rates of 34%, 29%, and 11%, respectively. Under multivariate analysis, and adjusting for the center effect and the occurrence of FCH, factors associated with better survival after retransplantation were: negative HCV viremia before retransplantation, antiviral therapy after retransplantation, non-genotype 1, a Model for End-stage Liver Disease (MELD) score < 25 when replaced on the waiting list, and a retransplantation donor age < 60 years. Although the numbers were small, in the context of the new antivirals era, we showed that outcomes in patients who underwent retransplantation with undetectable HCV viremia did not depend on donor age and MELD score. The Andres score was applied to 102 patients for whom all score variables were available, producing a mean score of 43.4 (SD = 6.6). Survival rates after the date of the first decompensation post-first liver transplantation (LT1) in the liver retransplantation (reLT) group (94 patients decompensated) at 3, 5, and 10 years were 62%, 59%, and 51%, respectively, among 78 retransplanted individuals with advanced cirrhosis, and 42%, 32%, and 16% among 16 retransplanted individuals with FCH. In the non-reLT group with hepatic decompensation, survival rates were 27%, 18%, and 9% at 3, 5, and 10 years, respectively (P < 0.0001). Compared with non-retransplanted patients, retransplanted patients were younger at LT1 (mean age 48 +/- 8 years compared to 53 +/- 9 years in the no reLT group, P < 0.0001), less likely to have human immunodeficiency virus (HIV) co-infection (4% vs 14% among no reLT patients, P = 0.005), more likely to have received corticosteroid bolus therapy after LT1 (25% in reLT vs 12% in the no reLT group, P = 0.01), and more likely to have presented with sustained virological response (SVR) after the first transplantation (20% in the reLT group vs 7% in the no reLT group, P = 0.028). CONCLUSION: Antiviral therapy before and after retransplantation had a substantial impact on survival in the context of retransplantation for HCV recurrence, and with the new direct acting antivirals now available, outcomes should be even better in the future. PMID- 27182166 TI - Methylation of DAPK and THBS1 genes in esophageal gastric-type columnar metaplasia. AB - AIM: To explore methylation of DAPK, THBS1, CDH-1, and p14 genes, and Helicobacter pylori (H. pylori) status in individuals harboring esophageal columnar metaplasia. METHODS: Distal esophageal mucosal samples obtained by endoscopy and histologically diagnosed as gastric-type (non-specialized) columnar metaplasia, were studied thoroughly. DNA was extracted from paraffin blocks, and methylation status of death-associated protein kinase (DAPK), thrombospondin-1 (THBS1), cadherin-1 (CDH1), and p14 genes, was examined using a methyl-sensitive polymerase chain reaction (MS-PCR) and sodium bisulfite modification protocol. H. pylori cagA status was determined by PCR. RESULTS: In total, 68 subjects (33 females and 35 males), with a mean age of 52 years, were included. H. pylori cagA positive was present in the esophageal gastric-type metaplastic mucosa of 18 individuals. DAPK, THSB1, CDH1, and p14 gene promoters were methylated by MS-PCR in 40 (58.8%), 33 (48.5%), 46 (67.6%), and 23 (33.8%) cases of the 68 esophageal samples. H. pylori status was associated with methylation of DAPK (P = 0.003) and THBS1 (P = 0.019). CONCLUSION: DNA methylation occurs in cases of gastric-type (non-specialized) columnar metaplasia of the esophagus, and this modification is associated with H. pylori cagA positive infection. PMID- 27182167 TI - Correlation between Helicobacter pylori-associated gastric diseases and colorectal neoplasia. AB - AIM: To explore the correlation between Helicobacter pylori (H. pylori) associated gastric diseases and colorectal neoplasia. METHODS: Patients included in this study underwent a colonoscopy and esophago-gastro-duodenoscopy (EGD) along with histopathological measurement between March 2012 and March 2015 at Qi Lu Hospital of Shandong University, who also had results of H. pylori detection. A total of 233 cases were selected. Demographic data, H. pylori infection status (including results of rapid urease tests and gastric mucosa pathological examinations) and histopathological examination results of gastric and colorectal mucosa were gathered and analyzed. The statistical analysis focused on the prevalence of colorectal neoplasms among patients with various histopathological categories of the stomach. ORs and their 95%CI were calculated to describe the strengths of the associations. RESULTS: The incidence rates of colorectal adenoma without high-grade intraepithelial neoplasia (HGIEN) (OR = 2.400, 95%CI: 0.969 5.941), adenoma with HGIEN (5.333, 1.025-27.758) and adenocarcinoma (1.455, 0.382 5.543) were all higher for patients with H. pylori-associated gastritis than for those in the control group. The incidence rate of colorectal adenoma with HGIEN (3.218, 0.767-13.509) was higher in patients with intestinal metaplasia than in the control group, while the incidence rates of adenoma without HGIEN (0.874, 0.414-1.845) and adenocarcinoma (0.376, 0.096-1.470) were lower in the intestinal metaplasia group than in the control group. The incidence rate of colorectal adenoma without HGIEN (3.111, 1.248-7.753) was significantly higher in the gastric intraepithelial neoplasia group than in the control group, while the rates of adenoma with HGIEN (1.481, 0.138-15.941) and adenocarcinoma (2.020, 0.561-7.272) were higher in the gastric intraepithelial neoplasia group. Incidence rates of colorectal adenoma without HGIEN (1.067, 0.264-4.314), adenoma with HGIEN (2.667, 0.231-30.800) and adenocarcinoma (2.182, 0.450-10.585) were all higher in the gastric adenocarcinoma group than in the control group. CONCLUSION: H. pylori infection as well as H. pylori-associated gastric diseases are risk factors for colorectal neoplasia. PMID- 27182168 TI - Changes in patients' symptoms and gastric emptying after Helicobacter pylori treatment. AB - AIM: To investigate the changes in clinical symptoms and gastric emptying and their association in functional dyspepsia (FD) patients. METHODS: Seventy FD patients were enrolled and divided into 2 groups Helicobacter pylori (H. pylori) negative group (28 patients), and H. pylori-positive group (42 patients). Patients in the H. pylori-positive group were further randomly divided into groups: H. pylori-treatment group (21 patients) and conventional treatment group (21 patients). Seventy two healthy subjects were selected as the control group. The proximal and distal stomach area was measured by ultrasound immediately after patients took the test meal, and at 20, 40, 60 and 90 min; then, gastric half emptying time was calculated. The incidence of symptoms and gastric half-emptying time between the FD and control groups were compared. The H. pylori-negative and conventional treatment groups were given conventional treatment: domperidone 0.6 mg/(kg/d) for 1 mo. The H. pylori-treatment group was given H. pylori eradication treatment + conventional treatment: lansoprazole 30 mg once daily, clarithromycin 0.5 g twice daily and amoxicillin 1.0 g twice daily for 1 wk, then domperidone 0.6 mg/(kg/d) for 1 mo. The incidence of symptoms and gastric emptying were compared between the FD and control groups. The relationship between dyspeptic symptoms and gastric half-emptying time in the FD and control groups were analyzed. Then total symptom scores before and after treatment and gastric half emptying time were compared among the 3 groups. RESULTS: The incidence of abdominal pain, epigastric burning sensation, abdominal distension, nausea, belching, and early satiety symptoms in the FD group were significantly higher than in the control group (50.0% vs 20.8%; 37.1% vs 12.5%; 78.6% vs 44.4%; 45.7% vs 22.2%; 52.9% vs 15.3%; 57.1% vs 19.4%; all P < 0.05). The gastric half emptying times of the proximal end, distal end, and the whole stomach in the FD group were slower than in the control group (93.7 +/- 26.2 vs 72.0 +/- 14.3; 102.2 +/- 26.4 vs 87.5 +/- 18.2; 102.1 +/- 28.6 vs 78.3 +/- 14.1; all P < 0.05). Abdominal distension, belching and early satiety had an effect on distal gastric half-emptying time (P < 0.05). Abdominal distension and abdominal pain had an effect on the gastric half-emptying time of the whole stomach (P < 0.05). All were risk factors (odds ratio > 1). The total symptom score of the 3 groups after treatment was lower than before treatment (P < 0.05). Total symptom scores after treatment in the H. pylori-treatment group and H. pylori-negative group were lower than in the conventional treatment group (5.15 +/- 2.27 vs 7.02 +/- 3.04, 4.93 +/- 3.22 vs 7.02 +/- 3.04, All P < 0.05). The gastric half-emptying times of the proximal end, distal end, and the whole stomach in the H. pylori-negative and H. pylori-treatment groups were shorter than in the conventional treatment group (P < 0.05). CONCLUSION: FD patients have delayed gastric emptying. H. pylori infection treatment helps to improve symptoms of dyspepsia and is a reasonable choice for treatment in clinical practice. PMID- 27182169 TI - Calcium supplementation for the prevention of colorectal adenomas: A systematic review and meta-analysis of randomized controlled trials. AB - AIM: To determine the efficacy of calcium supplementation in reducing the recurrence of colorectal adenomas. METHODS: We conducted a systematic review and meta-analysis of published studies. We searched PubMed, Scopus, the Cochrane Library, the WHO International Clinical Trials Registry Platform, and the ClinicalTrials.gov website, through December 2015. Randomized, placebo-controlled trials assessing supplemental calcium intake for the prevention of recurrence of adenomas were eligible for inclusion. Two reviewers independently selected studies based on predefined criteria, extracted data and outcomes (recurrence of colorectal adenomas, and advanced or "high-risk" adenomas), and rated each trial's risk-of-bias. Between-study heterogeneity was assessed, and pooled risk ratio (RR) estimates with their 95% confidence intervals (95%CI) were calculated using fixed- and random-effects models. To express the treatment effect in clinical terms, we calculated the number needed to treat (NNT) to prevent one adenoma recurrence. We also assessed the quality of evidence using GRADE. RESULTS: Four randomized, placebo-controlled trials met the eligibility criteria and were included. Daily doses of elemental calcium ranged from 1200 to 2000 mg, while the duration of treatment and follow-up of participants ranged from 36 to 60 mo. Synthesis of intention-to-treat data, for participants who had undergone follow-up colonoscopies, indicated a modest protective effect of calcium in prevention of adenomas (fixed-effects, RR = 0.89, 95%CI: 0.82-0.96; random effects, RR = 0.87, 95%CI: 0.77-0.98; high quality of evidence). The NNT was 20 (95%CI: 12-61) to prevent one colorectal adenoma recurrence within a period of 3 to 5 years. On the other hand, the association between calcium treatment and advanced adenomas did not reach statistical significance (fixed-effects, RR = 0.92, 95%CI: 0.75-1.13; random-effects, RR = 0.92, 95%CI: 0.71-1.18; moderate quality of evidence). CONCLUSION: Our results suggest a modest chemopreventive effect of calcium supplements against recurrent colorectal adenomas over a period of 36 to 60 mo. Further research is warranted. PMID- 27182172 TI - Prandial Insulin Dosing: How Long Does It Take to Go 80 Miles? PMID- 27182171 TI - Isolated splenic metastasis from colon cancer: Case report. AB - Isolated splenic metastases from colorectal cancer are very rare clinical entities and when they are present, they usually manifest widely disseminated disease. In this paper we report a case of metachronous solitary isolated splenic metastasis from colon cancer in a 64-year-old woman who was successfully treated by laparoscopic splenectomy. We discuss the pathological and clinical aspects of this condition. We furthermore comment on the diagnostic and therapeutic options of this rare entity through our observation of the case and consideration of the 31 case reports published in the literature. PMID- 27182170 TI - Pseudo-Meigs' syndrome secondary to metachronous ovarian metastases from transverse colon cancer. AB - Pseudo-Meigs' syndrome associated with colorectal cancer is extremely rare. We report here a case of pseudo-Meigs' syndrome secondary to metachronous ovarian metastases from colon cancer. A 65-year-old female with a history of surgery for transverse colon cancer and peritoneal dissemination suffered from metachronous ovarian metastases during treatment with systemic chemotherapy. At first, neither ascites nor pleural effusion was observed, but she later complained of progressive abdominal distention and dyspnea caused by rapidly increasing ascites and pleural effusion and rapidly enlarging ovarian metastases. Abdominocenteses were repeated, and cytological examinations of the fluids were all negative for malignant cells. We suspected pseudo-Meigs' syndrome, and bilateral oophorectomies were performed after thorough informed consent. The patient's postoperative condition improved rapidly after surgery. We conclude that pseudo Meigs' syndrome should be included in the differential diagnosis of massive or rapidly increasing ascites and pleural effusion associated with large or rapidly enlarging ovarian tumors. PMID- 27182174 TI - Diabetes Management Before and During Pregnancy: Preface. PMID- 27182175 TI - Guest Editor. PMID- 27182173 TI - Macronutrient Composition or Social Determinants? Impact on Infant Outcomes With Gestational Diabetes Mellitus. AB - The purpose of this study was to examine, through a randomized, controlled trial, the effects of a maternal carbohydrate-restricted diet on maternal and infant outcomes in gestational diabetes mellitus (GDM). Women diagnosed with GDM were randomly allocated into one of two groups: an intervention group that was placed on a lower-carbohydrate diet (35-40% of total calories) or a control group that was placed on the usual pregnancy diet (50-55% carbohydrate). A convenience sample of participants diagnosed with GDM (ages 18-45 years) was recruited from two different sites: one urban and low-income and the other suburban and more affluent. Individual face-to-face diet instruction occurred with certified diabetes educators at both sites. Participants tested their blood glucose four times daily. Specific socioeconomic status indicators included enrollment in the Supplemental Nutrition Program for Women, Infants and Children or Medicaid-funded health insurance, as well as cross-sectional census data. All analyses were based on an intention to treat. Although there were no differences found between the lower-carbohydrate and usual-care diets in terms of blood glucose or maternal infant outcomes, there were significant differences noted between the two sites. There was a lower mean postprandial blood glucose (100.59 +/- 7.3 mg/dL) at the suburban site compared to the urban site (116.3 +/- 15 mg/dL) (P <0.01), even though there was no difference in carbohydrate intake. There were increased amounts of protein and fat consumed at the suburban site (P <0.01), as well as lower infant complications (P <0.01). Further research is needed to determine whether these disparities in outcomes were the result of macronutrient proportions or environmental conditions. PMID- 27182177 TI - Carbohydrate Content in the GDM Diet: Two Views: View 2: Low-Carbohydrate Diets Should Remain the Initial Therapy for Gestational Diabetes. AB - IN BRIEF The appropriate dietary intervention for gestational diabetes mellitus (GDM) is not clear. Traditionally, a low-carbohydrate diet has been prescribed. Recently, there has been a movement to prescribe a diet higher in nutrient-dense carbohydrate as the initial treatment for GDM. At this time, there is insufficient outcome data to support this type of diet. PMID- 27182176 TI - Carbohydrate Content in the GDM Diet: Two Views: View 1: Nutrition Therapy in Gestational Diabetes: The Case for Complex Carbohydrates. AB - IN BRIEF Restriction of dietary carbohydrate has been the cornerstone for treatment of gestational diabetes mellitus (GDM). However, there is evidence that a balanced liberalization of complex carbohydrate as part of an overall eating plan in GDM meets treatment goals and may mitigate maternal adipose tissue insulin resistance, both of which may promote optimal metabolic outcomes for mother and offspring. PMID- 27182178 TI - Insulin Use in Pregnancy: An Update. AB - IN BRIEF Insulin remains the standard of care for the treatment of type 1 diabetes, type 2 diabetes, and uncontrolled gestational diabetes. Tight control maintained in the first trimester and throughout pregnancy plays a vital role in decreasing poor fetal outcomes, including structural anomalies, macrosomia, hypoglycemia of the newborn, adolescent and adult obesity, and diabetes. Understanding new insulin formulations and strengths is important in assessing risks, since no data on their use in human pregnancy exist. PMID- 27182179 TI - Oral Medications for Diabetes in Pregnancy: Use in a Rural Population. AB - IN BRIEF The oral agents glyburide and metformin are both recommended by many professional societies for the treatment of gestational diabetes mellitus (GDM). Both therapeutic modalities have published safety and efficacy data, but there remains much debate among experts. Providers need a clear treatment plan for GDM based on a predictable level of clinical success in obtaining treatment goals. The proper selection of ideal candidates is paramount in achieving clinical success with the use of these medications in the treatment of GDM. This article presents clinical strategies for using oral agents in the management of GDM based on a pragmatic approach taken in a group of rural Native American women. PMID- 27182180 TI - The Challenges of Providing Diabetes Education in Resource-Limited Settings to Women With Diabetes in Pregnancy: Perspectives of an Educator. AB - IN BRIEF In resource-limited settings, the challenges of providing diabetes education are magnified. To provide the best education, these challenges and barriers need to be identified and addressed. Many times, at the "teachable moment" of a gestational diabetes diagnosis, we are able to not only address the immediate concerns, but also help patients adopt and continue long-term healthy lifestyle behaviors that improve the health of their entire family. PMID- 27182181 TI - Implementation of Preconception Care for Women With Diabetes. AB - IN BRIEF Women with diabetes who are of reproductive age should receive preconception risk assessment and counseling to maximize pregnancy outcomes. This article summarizes the concept of preconception care for women with diabetes and provides a description of an implementation of collaborative preconception care for primary care and obstetrics and gynecology specialty providers. PMID- 27182182 TI - Evaluation of an Education Intervention in Hispanic Women at Risk for Gestational Diabetes Mellitus. PMID- 27182183 TI - Augmenting Telemonitoring Interventions by Targeting Patient Needs in a Primarily Hispanic Underserved Population. PMID- 27182184 TI - Arithmetic, reading and writing performance has a strong genetic component: A study in primary school children. AB - Even children attending the same primary school and taught by the same teacher differ greatly in their performance. In the Netherlands, performance at the end of primary school determines the enrollment in a particular level of secondary education. Identifying the impact of genes and the environment on individual differences in educational achievement between children is important. The Netherlands Twin Register has collected data on scores of tests used in primary school (ages 6 to 12) to monitor a child's educational progress in four domains, i.e. arithmetic, word reading, reading comprehension and spelling (1058 MZ and 1734 DZ twin pairs), and of a final test (2451 MZ and 4569 DZ twin pairs) in a large Dutch cohort. In general, individual differences in educational achievement were to a large extent due to genes and the influence of the family environment was negligible. Moreover, there is no evidence for gender differences in the underlying etiology. PMID- 27182185 TI - Structuring Health in Colorectal Cancer Screening Conversations: An Analysis of Intersecting Activity Systems. AB - This study used structurating activity theory to analyze 21 conversations between genetic counselors and individuals at increased risk for familial colorectal cancer (CRC). The qualitative analysis revealed ways elements of family, primary healthcare, cancer prevention and treatment, and other systems emerged in intervention conversations as shaping CRC screening attitudes and behaviors. Results indicate that family stories, norms, and roles are resources for enacting health practices in families and that the authority of healthcare providers is a resource for making screening decisions. Conclusions include practical implications for using findings in clinical applications as well as future research directions to build on this exploratory study. PMID- 27182186 TI - Photoshop(r) Assisted Spectroscopy: An Economical and Non-Destructive Method for Tracking Color Shift. AB - Many historically and culturally significant objects from the mid-to-late 20th century were created with media which contains light sensitive dyes that present problems for collection custodians and conservators. The conservation staff at the National Library of Medicine (NLM), National Institutes of Health, conducted a multi-phase project on the aging of ballpoint pen ink in a variety of enclosure types that ultimately culminated in the development of a new method to detect color shift in documents with light sensitive media. This article offers instructions on how to detect color shift in digitized materials using Photoshop(r) Assisted Spectroscopy. PMID- 27182188 TI - Rate-Agnostic (Causal) Structure Learning. AB - Causal structure learning from time series data is a major scientific challenge. Extant algorithms assume that measurements occur sufficiently quickly; more precisely, they assume approximately equal system and measurement timescales. In many domains, however, measurements occur at a significantly slower rate than the underlying system changes, but the size of the timescale mismatch is often unknown. This paper develops three causal structure learning algorithms, each of which discovers all dynamic causal graphs that explain the observed measurement data, perhaps given undersampling. That is, these algorithms all learn causal structure in a "rate-agnostic" manner: they do not assume any particular relation between the measurement and system timescales. We apply these algorithms to data from simulations to gain insight into the challenge of undersampling. PMID- 27182187 TI - African American patients' intent to screen for colorectal cancer: Do cultural factors, health literacy, knowledge, age and gender matter? AB - African Americans have higher colorectal cancer (CRC) mortality rates. Research suggests that CRC screening interventions targeting African Americans be based upon cultural dimensions. Secondary analysis of data from African-Americans who were not up-to-date with CRC screening (n=817) was conducted to examine: 1) relationships among cultural factors (i.e., provider trust, cancer fatalism, health temporal orientation (HTO)), health literacy, and CRC knowledge; 2) age and gender differences; and 3) relationships among the variables and CRC screening intention. Provider trust, fatalism, HTO, health literacy and CRC knowledge had significant relationships among study variables. The FOBT intention model explained 43% of the variance with age and gender being significant predictors. The colonoscopy intention model explained 41% of the variance with gender being a significant predictor. Results suggest that when developing CRC interventions for African Americans, addressing cultural factors remain important, but particular attention should be given to the age and gender of the patient. PMID- 27182189 TI - Integrating Genetics and Medicine: Disease-Modifying Treatment Strategies for Hypertrophic Cardiomyopathy. PMID- 27182190 TI - Statewide CBT Training for Clinicians and Supervisors Treating Youth: The New York State Evidence Based Treatment Dissemination Center. AB - In recent years, several states have undertaken efforts to disseminate evidence based treatments to agencies and clinicians in their children's service system. In New York, the Evidence Based Treatment Dissemination Center adopted a unique translation-based training and consultation model in which an initial 3-day training was combined with a year of clinical consultation with specific clinician and supervisor elements. This model has been used by the New York State Office of Mental Health for the past 3 years to train 1,210 clinicians and supervisors statewide. This article describes the early adoption and initial implementation of a statewide training program in cognitive-behavioral therapy for youth. The training and consultation model and descriptive findings are presented; lessons learned are described. Future plans include a focus on sustainability and measurement feedback of youth outcomes to enhance the continuity of this program and the quality of the clinical services. PMID- 27182191 TI - Perfectly Wetting Mixtures of Surfactants from Renewable Resources: The Interaction and Synergistic Effects on Adsorption and Micellization. AB - This paper presents a study of the surface properties of mixtures of surfactants originating from renewable sources, i.e., alkylpolyglucoside (APG), ethoxylated fatty alcohol (AE), and sodium soap (Na soap). The main objective was to optimize the surfactant ratio which produces the highest wetting properties during the analysis of the solution of the individual surfactants, two- and three-component mixtures, and at different pH values. The results showed the existence of a synergistic effect in lowering the interfacial tension, critical micelle concentration and the formation of mixed micelles in selected solutions. We found that best wetting properties were measured for the binary AE:APG mixtures. It has been demonstrated that slightly lower contact angles values were observed on Teflon and glass surfaces for the AE:APG:soap mixtures but the results were obtained for higher concentration of the components. In addition, all studied solutions have very good surface properties in acidic, basic and neural media. However, the AE:soap (molar ratio of 1:2), AE:APG (2:1) and AE:APG:soap (1:1:1) compositions improved their wetting power at pH 7 on the aluminium and glass surfaces, as compared to solutions at other pH values tested (selected Theta values close to zero-perfectly wetting liquids). All described effects detected would allow less surfactant to be used to achieve the maximum capacity of washing, wetting or solubilizing while minimizing costs and demonstrating environmental care. PMID- 27182192 TI - Benchmarking the Self-Assembly of Surfactin Biosurfactant at the Liquid-Air Interface to those of Synthetic Surfactants. AB - The adsorption of surfactin, a lipopeptide biosurfactant, at the liquid-air interface has been investigated in this work. The maximum adsorption density and the nature and the extent of lateral interaction between the adsorbed surfactin molecules at the interface were estimated from surface tension data using the Frumkin model. The quantitative information obtained using the Frumkin model was also compared to those obtained using the Gibbs equation and the Langmuir Szyszkowski model. Error analysis showed a better agreement between the experimental and the calculated values using the Frumkin model relative to the other two models. The adsorption of surfactin at the liquid-air interface was also compared to those of synthetic anionic, sodium dodecylbenzenesulphonate (SDBS), and nonionic, octaethylene glycol monotetradecyl ether (C14E8), surfactants. It has been estimated that the area occupied by a surfactin molecule at the interface is about 3- and 2.5-fold higher than those occupied by SDBS and C14E8 molecules, respectively. The interaction between the adsorbed molecules of the anionic biosurfactant (surfactin) was estimated to be attractive, unlike the mild repulsive interaction between the adsorbed SDBS molecules. PMID- 27182193 TI - Insight on the Li2S electrochemical process in a composite configuration electrode. AB - A novel, low cost and environmentally sustainable lithium sulfide-carbon composite cathode, suitably prepared by combining polyethylene oxide (PEO), LiCF3SO3 and Li2S-C powders is here presented. The cathode is characterized in lithium-metal cell employing a solution of LiCF3SO3 salt in dioxolane dimethylether (DOL-DME) as the electrolyte. Detailed NMR investigation of the diffusion properties of the electrolyte is reported in order to determine its suitability for the proposed cell. The addition of LiNO3 to the electrolyte solution allows practical application in a lithium sulfur cell using the Li2S-C based cathode characterized by a specific capacity of about 500 mAh g-1 (as referenced to the Li2S mass). The cell holds its optimal performances for over 70 cycles at C/5 rate, with a steady state efficiency approaching 99%. X-ray diffraction patterns of the cell upon operation suggest the reversibility of the Li2S electrochemical process, while repeated electrochemical impedance spectroscopy (EIS) measurements indicate the suitability of the electrode electrolyte interface in terms of low and stable cell impedance. Furthermore, the EIS study clarifies the activation process occurring at the Li2S cathode during the first charge process, leading to the decrease of the cell polarization during the following cycles. The data here reported shed light on important aspects to be considered for the efficient application of the Li2S cathode in lithium battery. PMID- 27182195 TI - Racism: On the phenomenology of embodied desocialization. AB - This paper addresses racism from a phenomenological viewpoint. Its main task is, ultimately, to show that racism as a process of "negative socialization" does not amount to a contingent deficiency that simply disappears under the conditions of a fully integrated society. In other words, I suspect that racism does not only indicate a lack of integration, solidarity, responsibility, recognition, etc.; rather, that it is, in its extraordinary negativity, a socially constitutive phenomenon per se. After suggesting phenomenology's potential to tackle the question of racism, I will focus on the experiential oppressiveness of racism, i.e., the ways in which it affects its victims' lived experiences, in transforming their habitual ways of life and, finally, their subjectivities. My major thesis is that racism works via both inter-kinaesthetically as well as symbolically inflicted distortions of the victim's body schema. As such a process of "negative socialization," racism, however, influences the embodied self conception of the oppressor, who finds himself compelled to adhere to some kind of invisible norm such as, e.g., "whiteness." PMID- 27182194 TI - Strategies and Methods for the Synthesis of Anticancer Natural Product Neopeltolide and its Analogs. AB - Neopeltolide, isolated in 2007, with its novel structural features and potent anti cancer cell proliferation activity, has attracted a tremendous amount of synthetic efforts. This review briefly and chronologically summarizes each of the synthesis with the main focus on the strategies and methodologies for the construction of its cis-tetrahydropyran-containing macrolactone core. PMID- 27182197 TI - Guest editorial: special issue on selected papers from the European conference on genetic programming. PMID- 27182196 TI - From the "metaphysics of the individual" to the critique of society: on the practical significance of Michel Henry's phenomenology of life. AB - This essay explores the practical significance of Michel Henry's "material phenomenology." Commencing with an exposition of his most basic philosophical intuition, i.e., his insight that transcendental affectivity is the primordial mode of revelation of our selfhood, the essay then brings to light how this intuition also establishes our relation to both the world and others. Animated by a radical form of the phenomenological reduction, Henry's material phenomenology brackets the exterior world in a bid to reach the concrete interior transcendental experience at the base of all exteriority. The essay argues that this "counter reduction," designed as a practical orientation to the world, suspends all traditional parameters of onto(theo)logical individuation in order to rethink subjectivity in terms of its transcendental corporeality, i.e., in terms of the invisible display of "affective flesh." The development of this "metaphysics of the individual" anchors his "practical philosophy" as he developed it-under shifting accents-throughout his oeuvre. In particular, the essay brings into focus Henry's reflections on modernity, the industry of mass culture and their "barbaric" movements. The essay briefly puts these cultural and political areas of Henry's of thinking into contact with his late "theological turn," i.e., his Christological account of Life and the (inter)subjective self realization to which it gives rise. PMID- 27182198 TI - Migration and Marriage: Modeling the Joint Process. AB - BACKGROUND: Previous research on inter-relations between migration and marriage has relied on overly simplistic assumptions about the structure of dependency between the two events. However, there is good reason to posit that each of the two transitions has an impact on the likelihood of the other, and that unobserved common factors may affect both migration and marriage, leading to a distorted impression of the causal impact of one on the other. OBJECTIVE: We will investigate relationships between migration and marriage in the United States using data from the National Longitudinal Survey of Youth 1979. We allow for inter-dependency between the two events and examine whether unobserved common factors affect the estimates of both migration and marriage. METHODS: We estimate a multi-process model in which migration and marriage are considered simultaneously in regression analysis and there is allowance for correlation between disturbances; the latter feature accounts for possible endogeneity between shared unobserved determinants. The model also includes random effects for persons, exploiting the fact that many people experience both events multiple times throughout their lives. RESULTS: Unobserved factors appear to significantly influence both migration and marriage, resulting in upward bias in estimates of the effects of each on the other when these shared common factors are not accounted for. Estimates from the multi-process model indicate that marriage significantly increases the hazard of migration while migration does not affect the hazard of marriage. CONCLUSIONS: Omitting inter-dependency between life course events can lead to a mistaken impression of the direct effects of certain features of each event on the other. PMID- 27182199 TI - First- and second-hand consequences of alcohol in college: Differential associations with later alcohol use. AB - INTRODUCTION: College students are at increased risk of experiencing a variety of consequences as result of their own as well as others' alcohol consumption. The current study examined the differential associations between both first-hand consequences (resulting from one's own drinking) and second-hand consequences (resulting in victimization as a result of others' drinking) and subsequent alcohol consumption across the first year of college. METHOD: First year students (n = 253) from a large northeastern U.S. university were randomly selected to participate and surveyed at the end of the first semester of college (time 1) and during the first semester of the second year of college (time 2). RESULTS: Results showed a significant, positive relationship between first-hand consequences and subsequent weekend drinking (beta = .16, p < .05) and heavy episodic drinking (beta = .49, p < .01), after controlling for individual and friend drinking. A negative association between second-hand consequences and later heavy episodic drinking was also observed (beta = -.16, p < .05). DISCUSSION AND CONCLUSIONS: The findings provided partial support for both a positive association hypothesis and a negative association hypothesis. The importance of personal alcohol consumption and peers' drinking in relation to first- and second-hand consequences are discussed. PMID- 27182201 TI - The 'visibility' of unpaid care in England. AB - SUMMARY: Social work practice is increasingly concerned with support not just for service users but also for unpaid carers. A key aspect of practice is the assessment of carers' needs. The Government has recently passed legislation that will widen eligibility for carers' assessments and remove the requirement that carers must be providing a substantial amount of care on a regular basis. This article examines which carers are currently 'visible' or known to councils and which are not, and uses the results to examine the likely effects of the new legislation. In order to identify the characteristics of carers known to councils, the article uses large-scale surveys, comparing the 2009/10 Personal Social Services Survey of Adult Carers in England and the 2009/10 Survey of Carers in Households in England. FINDINGS: Carers who are known to councils provide extremely long hours of care. Among carers providing substantial care who are known to councils, the majority care for 100 or more hours a week. The focus of councils on carers providing long hours of care is associated with a number of other carer characteristics, such as poor health. APPLICATIONS: Councils' emphasis on the most intense carers is unlikely to be attributable solely to the current legislation. Therefore, dropping the substantial and regular clauses alone will not necessarily broaden access to carers' assessments and, in order to achieve this, considerable new resources may be needed. How far these resources are available will determine the extent to which practitioners can broaden access to carers' assessments. PMID- 27182200 TI - The influence of family and social problems on treatment outcomes of persons with co-occurring substance use disorders and PTSD. AB - OBJECTIVE: Family and social problems may contribute to negative recovery outcomes in patients with co-occurring substance use and psychiatric disorders, yet few studies have empirically examined this relationship. This study investigates the impact of family and social problems on treatment outcomes among patients with co-occurring substance use and posttraumatic stress disorder (PTSD). METHOD: A secondary analysis was conducted using data collected from a randomized controlled trial of an integrated therapy for patients with co occurring substance use and PTSD. Substance use, psychiatric symptoms, and social problems were assessed. Longitudinal outcomes were analyzed using generalized estimating equations (GEE) and multiple linear regression. RESULTS: At baseline, increased family and social problems were associated with more severe substance use and psychiatric symptoms. Over time, all participants had comparable decreases in substance use and psychiatric problem severity. However, changes in family and social problem severity were predictive of PTSD symptom severity, alcohol use, and psychiatric severity at follow-up. CONCLUSIONS: For patients with co-occurring substance use and PTSD, family and social problem severity is associated with substance use and psychiatric problem severity at baseline and over time. Targeted treatment for social and family problems may be optimal. PMID- 27182202 TI - Lyn, a tyrosine kinase closely linked to the differentiation status of primary acute myeloid leukemia blasts, associates with negative regulation of all-trans retinoic acid (ATRA) and dihydroxyvitamin D3 (VD3)-induced HL-60 cells differentiation. AB - BACKGROUND: Lyn, an import member of Src family kinases (SFKs), is supposed to be implicated in acute myeloid leukemia (AML) pathogenesis and development by participation in AML differentiation, yet the details still remain incompletely understood. The expression status of Lyn and its correlation with multiple clinical parameters including cell differentiation degree, different cytogenetic risk classification, and the activity of myeloperoxidase (MPO) were thus investigated. To address the mechanisms underlying the involvement of Lyn in differentiation induction, the effects of dasatinib, an inhibitor for SFKs including Lyn, on the alterations of all-trans retinoic acid (ATRA)- or dihydroxyvitamin D3 (VD3)-induced differentiation, and c-Myc protein expression were investigated. METHODS: Primary AML blasts were obtained from 31 newly diagnosed AML patients with different French-American-British (FAB) subtypes. The expression of phosphorylated and total Lyn, c-Myc, and CD11b, CD11c and CD15 was analyzed by flow cytometry. The activation of Akt and Erk known to be involved in the regulation of c-Myc expression was investigated using western blotting. RESULTS: Significant higher expression levels of total Lyn were observed in AML patients with favorable cytogenetics, higher MPO activity and FAB M2 subtype. A clear positive correlation between the expression levels of Lyn and differentiation status of primary AML blasts was observed. Dasatinib inhibited the expression of phosphorylated Lyn, and further enhanced the differentiation inducing activity of ATRA and VD3 in HL-60 cells. Augmented downregulation of c Myc protein expression was observed in the combination treatment with ATRA, VD3 and dasatinib compared to treatment with each reagent alone in HL-60 cells. The suppression of the activation of Akt and Erk was also observed concomitantly. CONCLUSIONS: The expression level of total Lyn is closely linked to the differentiation status of AML blasts. The enhancement of differentiation-inducing activity of ATRA/VD3 by dasatinib suggested that Lyn was associated in the negative regulation of ATRA/VD3-induced HL-60 cells differentiation. The enhancement probably was attributed to the downregulation of c-Myc implicated with the suppression of the activation of Akt and Erk. These results provide novel insights into a possible combinational therapeutic approach by targeting Lyn for AML patients, and offer new possibilities for the combination therapy with VD3 and dasatinib. PMID- 27182203 TI - Development of a metric for tracking and comparing population health based on the minimal generic set of domains of functioning and health. AB - BACKGROUND: The following minimal set of valid health domains for tracking the health of both clinical and general populations has recently been proposed: 1) energy and drive functions, 2) emotional functions, 3) sensation of pain, 4) carrying out daily routine, 5) walking and moving around, and 6) remunerative employment. This study investigates whether these domains can be integrated into a sound psychometric measure to adequately assess, compare, and monitor the health of populations. METHODS: Data from waves 3 and 4 of the English Longitudinal Study of Ageing (ELSA) were analysed (N = 9779 and 11,050). From ELSA, 12 items operationalizing the six domains of the minimal generic set were identified. The Partial Credit Model (PCM) was applied to create a health metric based on these items. The Item Response Theory (IRT) model assumptions of unidimensionality, local independence, and monotonicity were evaluated, and Differential Item Functioning (DIF) was examined for sex and age groups. The psychometric properties of: 1) internal consistency reliability, 2) construct validity, and 3) sensitivity to change were evaluated to establish the final health metric. RESULTS: IRT model assumptions were found to be fulfilled. None of the items showed DIF by sex or age group. The final health metric demonstrated sound psychometric properties. CONCLUSIONS: The health metric developed in this study - based on the domains of the minimal generic set - proved useful for a wide range of health comparisons, especially for different groups of persons, and both cross-sectionally and over time. Monitoring health over time provides especially useful information for health care providers and health policymakers and both in clinical settings and the general population. The developed health metric offers a wide range of applications, including comparisons of levels of health among different groups in the general population, clinical populations, and even populations within and across different countries. PMID- 27182205 TI - Absolute Configuration and Polymorphism of 2-Phenylbutyramide and alpha-Methyl alpha-phenylsuccinimide. AB - Crystal structures of racemic and homochiral forms of 2-phenylbutyramide (1) and 3-methyl-3-phenylpyrrolidine-2,5-dione (2) were investigated in detail by a single crystal X-ray diffraction study. Absolute configurations of the homochiral forms of 1 and 2, obtained by chromatographic separation of racemates, were determined. It was revealed that racemate and homochiral forms of 1 are very similar in terms of supramolecular organization (H-bonded ribbons) in crystal, infrared (IR) spectral characteristics, and melting points. The presence of two different molecular conformations in homochiral forms of 1 allowed mimicking of crystal packing of the H-bonded ribbons in racemate 1. Two polymorph modifications (monoclinic and orthorhombic) comprising very similar H-bonded zigzag-like chains were found for the homochiral forms of compound 2 that were significantly different in terms of crystal structure, IR spectra, and melting points from the racemic form of 2. Unlike compound 1, homochiral forms of compound 2 have a higher density than the corresponding racemate which contradicts the Wallach rule and indicates that, in this case, homochiral forms are more stable than racemate forms. PMID- 27182204 TI - A Practical Approach to Quantitative Processing and Analysis of Small Biological Structures by Fluorescent Imaging. AB - Standards in quantitative fluorescent imaging are vaguely recognized and receive insufficient discussion. A common best practice is to acquire images at Nyquist rate, where highest signal frequency is assumed to be the highest obtainable resolution of the imaging system. However, this particular standard is set to insure that all obtainable information is being collected. The objective of the current study was to demonstrate that for quantification purposes, these correctly set acquisition rates can be redundant; instead, linear size of the objects of interest can be used to calculate sufficient information density in the image. We describe optimized image acquisition parameters and unbiased methods for processing and quantification of medium-size cellular structures. Sections of rabbit aortas were immunohistochemically stained to identify and quantify sympathetic varicosities, >2 MUm in diameter. Images were processed to reduce background noise and segment objects using free, open-access software. Calculations of the optimal sampling rate for the experiment were based on the size of the objects of interest. The effect of differing sampling rates and processing techniques on object quantification was demonstrated. Oversampling led to a substantial increase in file size, whereas undersampling hindered reliable quantification. Quantification of raw and incorrectly processed images generated false structures, misrepresenting the underlying data. The current study emphasizes the importance of defining image-acquisition parameters based on the structure(s) of interest. The proposed postacquisition processing steps effectively removed background and noise, allowed for reliable quantification, and eliminated user bias. This customizable, reliable method for background subtraction and structure quantification provides a reproducible tool for researchers across biologic disciplines. PMID- 27182206 TI - Ingestible Biosensors for Real-Time Medical Adherence Monitoring: MyTMed. AB - Medication nonadherence complicates the management and treatment of chronic disease. Nonadherence to medications is associated with significant mortality, accelerated disease progression, and increased health care costs. My/Treatment/Medication (MyTMed) is a novel adherence monitoring system that obtains direct measures of medication adherence/nonadherence. MyTMed consists of 1) a "digital pill" with a radiofrequency emitter that activates on contact with gastric pH; 2) a relay Hub that captures the radiofrequency signal and transmits it to 3) a cloud based server that connects patient and physicians via a bidirectional interface. In our increasingly mobile world, MyTMed is able to provide medication ingestion data and deliver interventions in real time that support adherence. We describe the patient-centered design of MyTMed as well as the behavioral theory supporting the interface architecture. PMID- 27182207 TI - Renal replacement Therapy and Barriers to choice: using a Mixed Methods approach to explore the Patient's Perspective. AB - Alternatives to in-center hemodialysis as treatment for end-stage renal disease have been shown to increase patient quality of life, decrease co-morbidities and decrease financial strain on both the patient and the health care system. Focus groups (n = 6 groups with 47 participants) and survey data (n = 113) were used to ascertain perceived barriers and facilitators to alternative therapies and psychosocial and educational issues that may affect a patients' choice of modality among patients utilizing in-center dialysis, home dialysis and renal transplantation. Fear emerged as a predominant theme, both at diagnosis and when choosing a modality. Distrust of the medical system, denial and patient experiences with previous modalities were seen as barriers to care. Results imply that interventions addressing fear and providing more comprehensive pre-dialysis education may decrease barriers. PMID- 27182209 TI - Diagnostic Testing. PMID- 27182208 TI - Characterizing magnetic resonance signal decay due to Gaussian diffusion: the path integral approach and a convenient computational method. AB - The influence of Gaussian diffusion on the magnetic resonance signal is determined by the apparent diffusion coefficient (ADC) and tensor (ADT) of the diffusing fluid as well as the gradient waveform applied to sensitize the signal to diffusion. Estimations of ADC and ADT from diffusion-weighted acquisitions necessitate computations of, respectively, the b-value and b-matrix associated with the employed pulse sequence. We establish the relationship between these quantities and the gradient waveform by expressing the problem as a path integral and explicitly evaluating it. Further, we show that these important quantities can be conveniently computed for any gradient waveform using a simple algorithm that requires a few lines of code. With this representation, our technique complements the multiple correlation function (MCF) method commonly used to compute the effects of restricted diffusion, and provides a consistent and convenient framework for studies that aim to infer the microstructural features of the specimen. PMID- 27182210 TI - Contemporary Understanding and Management of Overt and Covert Hepatic Encephalopathy. AB - Hepatic encephalopathy (HE) is a major complication of liver disease that leads to significant morbidity and mortality. Caring for hospitalized patients with HE is becoming more complex, and the economic burden of HE continues to rise. Defining and diagnosing HE, particularly covert HE (CHE), remain challenging. In this article, we review new tools and those currently under development for the diagnosis of CHE and the latest advances in the acute and long-term management of overt HE (OHE) and CHE. In particular, we review the latest data on the use of lactulose and rifaximin for treatment of OHE and summarize the data on adjunctive agents such as sodium benzoate and probiotics. PMID- 27182212 TI - The Relationship Between Hepatocellular Carcinoma and Hepatitis B and C Virus. PMID- 27182213 TI - European Experience of Infliximab Biosimilars for the Treatment of Inflammatory Bowel Disease. PMID- 27182215 TI - Liver Transplant in Patients With Primary Sclerosing Cholangitis. PMID- 27182211 TI - Fertility and Contraception in Women With Inflammatory Bowel Disease. AB - Inflammatory bowel disease (IBD) carries a high burden in women during their reproductive years, and family planning issues are often a significant cause of concern. Fertility is normal in women with nonsurgically treated ulcerative colitis and similar or slightly reduced in women with Crohn's disease. Women who undergo ileal pouch anastomosis have reduced fertility. Fertility is likely worsened by disease activity but unaffected by medications used to treat IBD. Infertile patients with IBD respond as well as non-IBD patients to in vitro fertilization (IVF). Despite normal fertility, patients with IBD have fewer children due to concerns regarding infertility, disease inheritance, congenital abnormalities, and disease-related sexual dysfunction. Patients rarely discuss these issues with a physician. When discussion does occur, it may lead to changes in decision-making. Contraceptives are an important part of family planning, particularly during times of high disease activity. All forms of contraceptives are acceptable in patients with IBD, although there are specific considerations. The risks of combined oral contraceptives outweigh the benefits in patients with active disease and patients with prior or high risk for thromboembolism. Oral contraceptives and IBD are independently associated with an increased risk for thromboembolism, although it is not known whether this effect is compounding. Depot medroxyprogesterone acetate injection should be avoided in patients with or at risk for osteopenia. Intrauterine devices and implants are the most effective form of contraception and should be a first-line recommendation. The use of oral contraceptives is associated with the development of IBD, although there is no increased risk of disease relapse with the use of any form of contraceptive. PMID- 27182214 TI - Helicobacter pylori Infection in the Era of Antibiotic Resistance. PMID- 27182216 TI - Management of Idiopathic and Iatrogenic Esophageal Perforations. PMID- 27182217 TI - GASTRO-HEP News. PMID- 27182218 TI - Evidence-Based Parenting Programs for Maltreating Parents: Views of Child Protective Services Caseworkers. PMID- 27182220 TI - Publish or Perish: Need to have another look? PMID- 27182219 TI - DNA G-quadruplex and its potential as anticancer drug target. AB - G-quadruplex secondary structures are four-stranded globular nucleic acid structures form in the specific DNA and RNA G-rich sequences with biological significance such as human telomeres, oncogene-promoter regions, replication initiation sites, and 5' and 3'-untranslated (UTR) regions. The non-canonical G quadruplex secondary structures can readily form under physiologically relevant ionic conditions and are considered to be new molecular target for cancer therapeutics. This review discusses the essential progress in our lab related to the structures and functions of biologically relevant DNA G-quadruplexes in human gene promoters and telomeres, and the opportunities presented for the development of G-quadruplex-targeted small- molecule drugs. PMID- 27182221 TI - How to write a Doctoral Thesis. PMID- 27182222 TI - Hepatorenal syndrome:Response to terlipressin and albumin and its determinants. AB - OBJECTIVE: To determine the efficacy of terlipressin and albumin in improving renal functions in patient with hepatorenal syndrome (HRS) and to identify factors determinant of better response. METHODS: In this quasi experimental interventional study patients of liver cirrhosis and ascites with HRS type I were treated with intravenous albumin and incremental dosage of terlipressin based on response with maximum dose of 12mg/day. Decline of creatinine below 1.5mg/dl was defined as complete response. Factors predictive of response to therapy were determined via linear regression analysis. RESULTS: Twenty four patients were included with male to female ratio 3.8/1(19/5) and mean age 53.3 (+/-10.06). Complete response to terlipressin/albumin was seen in 14 (58.3%)patients, seven (29.2%) achieved partial response with > 25% creatinine decline while three (12.5%) had no response. Lower serum creatinine at diagnosis (P value 0.003), absence of hyperkalemia (p value 0.005) and absence of portal vein thrombosis (p value 0.05) are associated with response to treatment in HRS. Baseline serum creatinine (p value 0.003) was independent predictor of response to therapy in multivariate analysis. CONCLUSION: Terlipressin and albumin is an effective treatment for HRS type I. Patients with lower baseline serum creatinine are more likely to respond to this therapy. PMID- 27182223 TI - Scientific publications in critical care medicine journals from East Asia: A 10 year survey of the literature. AB - OBJECTIVE: The quantity and quality of publications in critical care medicine from East Asia haven't been reported. This study aimed to investigate the contribution of publications from East Asia. METHODS: Articles from China, Japan and South Korea in 2005 to 2014 were retrieved from Web of Science and Pubmed. The number of publications, impact factor, citation, and article types were analyzed. RESULTS: There were 3076 publications from East Asia (1720 from China, 913 from Japan, and 443 from South Korea). There were a significant decrease in publications from Japan (p = 0.024) and significant increases from China (p = 0.000) and South Korea (p = 0.009). From 2006, the number of articles from China exceed Japan. China had the highest total impact factor (6618.48) and citation (18416), followed by Japan (4566.03; 15440) and South Korea (1998.19; 5599). Japan had the highest mean impact factor (5.00) and citations (16.91), followed by South Korea (4.51; 12.64) and China (3.85; 10.71). CONCLUSIONS: China and South Korea's contributions to critical care medicine had significant increases during the past 10 years, while Japan had a significant decrease. China was the most productive region in East Asia since 2006. Japan had the highest quality research output. PMID- 27182224 TI - Diagnostic utility of saline infusion doppler sonohysterography in endometrial mass lesions. AB - OBJECTIVE: To evaluate the importance of saline infusion Doppler sonohysterography (SIS-D) in the assessment of transvaginal ultrasound (TVUSG) suspected intrauterine mass lesions in women complaining about abnormal uterine bleeding with respect to hysteroscopy (H/S) and pathologic diagnosis. METHODS: This study was conducted on patients, who visited to our clinic with abnormal uterine bleeding and whose TVUSGs indicated intrauterine masses. The study covered a total of 100 patients. SIS-D and hysteroscopy were performed on those 100 patients. SIS-D results were compared with hysteroscopy results. The relation between SIS-D findings and pathology results were evaluated. RESULTS: For SIS; specificity was 96%, sensitivity was 60%, positive predictive value (PPV) was 87.8%, negative predictive value (NPV) was 83.3%, and the accuracy rate was 87%. For TVUSG; PPV was 75%. According to SIS-D, 92.2% of the lesions that had single vessel feeding patterns were endometrial polyps, and this was statistically significant (p<0.0001). 57.1% of the lesions that had multiple-vessel feeding patterns were submucous myomas, and this was statistically significant (p<0.0001). CONCLUSION: SIS should be performed in patients before hysteroscopy because it will protect a considerable number of patients from unnecessary invasive procedures. SIS-D gives an idea on the histopathology of the mass. PMID- 27182225 TI - The eating habits of Patients with Type 2 diabetes in Algeria. AB - OBJECTIVE: To evaluate the eating habits and the practice of physical-activity of patients with Tyhpe-2 diabetes. (DT2). METHODS: A total of 1523 patients DT2 with average age 58+/-9.9 were recruited. A questionnaire about their eating habits, physical activity was conducted. Data were analyzed using SPSS statistical. RESULTS: Most of the patients were obese (64%), with irregular and weak practice of the physical-activity. The patients based their consumption on food rich with nutrients of high glycaemic index. Their food was mainly characterized by high amounts of fats, the green salads and the desserts (fruits) represent only a secondary amount. Statistically, Overweight + obese patients with diabetes had significantly higher level of consumption of the bread. However, the normal weight patients with diabetes had significantly higher level of the consumption of fruit and vegetables (p=0.006 and p=0 respectively). On the other hand, there was no significant difference in level of the consumption of the greasy substances, milk and dairy products, meat-fish-egg two groups (p=0.53, p=0.06 and P > 0.05). CONCLUSION: This study showed the need for an improvement in the nutritional care of DT2 patients in the area of Ain Defla (Algeria), also, the practice of the physical-activity, in order to plan an adequate therapeutic care. PMID- 27182226 TI - Prevalence of anxiety and depression among doctors; the unscreened and undiagnosed clientele in Lahore, Pakistan. AB - OBJECTIVES: To analyze prevalence of anxiety and depression among doctors serving in a tertiary care hospital in Lahore, with a study of impact of relevant demographic features. METHODS: A cross sectional study was conducted at Combined Military Hospital, Lahore, from February 2014 to Jan 2015. Participants were doctors serving in subject hospital for at least six months duration. Standardized Hospital Anxiety Depression Score (HADS) inventory was selected as inventory. Formal approval from hospital ethical committee and written informed consent from participants were obtained. Demographic characteristics of participants were recorded as independent variables; anxiety and depression scores being outcome variables. Data analysis was done via descriptive statistics (SPSS-20), qualitative data expressed as frequencies, percentages; quantitative as mean +/- standard deviation(SD). Cross tabulation was done via chi-square, p value < 0.05 considered as significant. RESULTS: Out of 203 volunteers, 97(47.78%) responded. Score of anxiety was 7.04+/-4.470, maximum being 19, scores of depression was 4.94+/-3.605, maximum score being 15. Mild to moderate anxiety and depression were revealed in 33(34%) and 24(24.8%) respectively, while 7(7.2%) and 1(1.0%) had severe anxiety and depression respectively. There was strong positive relation between anxiety and depression (p<0.001). There was significant impact of service years on depression (p-0.011) and gender on anxiety (p-0.002), 9(17.31%) males and 24(53.33%) females had mild to moderate anxiety while 4(7.69%) males and 3(6.66%) females revealed severe anxiety and other variables did not reveal significant impact on HADS scores. CONCLUSION: Doctors showed high grades of anxiety and depression. They must be promptly screened and managed at all medical institutions. PMID- 27182227 TI - Comparison of Laparoscopic Appendectomy with open appendectomy in Treating Children with Appendicitis. AB - OBJECTIVE: To analyze feasibility and curative effect of laparoscopic appendectomy in the treatment of pediatric appendicitis and compare it with open appendectomy. METHODS: Two hundred and sixty patients were selected for this study and randomly divided into open appendectomy group (130 cases) and laparoscopic appendectomy group (130 cases). Patients in open appendectomy group underwent traditional open appendectomy, while patients in laparoscopic appendectomy were treated with laparoscopic appendectomy. Incision length, blood loss during operation, duration of operation, time to leave bed, anus exhausting time, time to take food, catheter drainage time, urinary catheterization time, time of using antibiotics, use of pain killer and incidence of complications such as incision infection, residual abscess and intestinal obstruction were compared between two groups. RESULTS: We found relevant indexes including length of incision, amount of bleeding and duration of operation in laparoscopic appendectomy group were better than open appendectomy group after surgery; and differences were statistically significant (P<0.05). Indexes such as time to out of bed, time to take food, exhaust time, drainage time, catheterization time and application time and use of antibiotics in laparoscopic appendectomy group were all superior to open appendectomy group, and differences had statistical significance (P<0.05). Incidence of complications in laparoscopic appendectomy group was much lower than open appendectomy group and the difference was statistically significant (P<0.05). CONCLUSION: Laparoscopic appendectomy has advantages of small trauma, sound curative effect, low incidence of complications and rapid recovery and can effectively relieve pain of children suffering from appendicitis. Hence it is worth promotion and should be preferred. PMID- 27182228 TI - Surgical outcome of spelenectomy in Thalassemia major in children. AB - OBJECTIVE: To determine the surgical outcome of splenectomy in children with thalassemia major. METHODS: It is an observational and descriptive study conducted in Department of Paediatric Surgery in collaboration with hematology, radiology, anesthesia and paediatric intensive care department at The Children's Hospital and the Institute of Child Health, Multan during the period of September 2007 to September 2013. A total of 50 patients suffering from thalassemia major already diagnosed and under management reffered from haematology department for splenectomy were included in this study. After admission, patients were assessed on the basis of history, clinical examination, and necessary investigations before surgery and later on follow-up. Investigations carried were CBC, PT, APTT, Viral markers, ECG, X-ray Chest, abdominal ultrasonography and ECHO if necessary. Splenectomy was performed after prophylactic vaccination against post splenectomy infections. Follow up was performed for at least two years. Blood transfusion requirements and number of hospital visits per annum before and after splenectomy were calculated and results analyzed statistically using SPSS-20. RESULTS: Fifty patients were included in this study. Out of these fifty, 43 (86%) male and 7(14%) were female with a mean age of 9 years. Average blood transfusion requirement was 250 ml/kg/year, interval of blood transfusion was two weeks and twenty five visits per year before splenectomy. After splenectomy, requirement of blood transfusion reduced to 125ml/kg/year, interval between transfusion increased to one month and hospital visits reduced up to twelve per year. CONCLUSION: Blood transfusion requirement and number of hospital visits per year are decreased and interval between transfusions is increased after splenectomy. Splenectomy should not be delayed when indicated. Preoperative vaccination decreases the chance of post splenectomy infection. PMID- 27182229 TI - Oxidative stress and antioxidant parameters in neutropenic patients secondary to chemotherapy. AB - OBJECTIVE: Neutropenia is a serious adverse event that necessitates dosage reduction in patients receiving chemotherapy. In this study, we evaluated the oxidative stress and antioxidant parameters in neutropenic patients after chemotherapy both during the neutropenic period and after successful treatment of neutropenia with filgrastim. METHODS: We studied paraoxonase (PON1), arylesterase (ARE), malondialdehyde (MDA), high-density lipoprotein (HDL), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP) in addition to routine biochemical and hematologic parameters. SPSS 12.0 was used for statistical evaluation of data (SPSS, Chicago, IL, USA). RESULTS: In our study, PON1, HDL, and LDH levels during the period of active neutropenia were statistically significantly higher than these levels were after resolution of neutropenia (P<0.05); MDA and ALP levels were statistically significantly lower during the period of active neutropenia (P<0.05). CONCLUSIONS: Overall, free oxygen radicals (FOR) were increased and antioxidant parameters were decreased with resolution of neutropenia. This is probably due to FOR produced by the increased number of neutrophils rather than tumor burden. PMID- 27182230 TI - Factors affecting mode of delivery in a nullipara at term with singleton pregnancy and vertex presentation (NTSV). AB - OBJECTIVE: To analyse the factors associated with Caesarean Section (CS) of Nulliparous, Term and Singleton pregnancies with Vertex presentation (NTSV) at a tertiary care hospital. METHODS: In this unmatched retrospective case-control study, 212 NTSV patients were identified through computerized medical record systems; the data was collected through predesigned Performa by reviewing medical record charts. One hundred six CS and spontaneous vaginal deliveries (SVD) were taken as cases and controls. RESULTS: The mean maternal age of cases (CS) was 26.64 (SD: 3.9) and of controls (SVD) was 26.7(SD: 3.9) years, whereas mean gestational age was 38.66+/-1.12 and 38.57+/-0.9 weeks for cases and controls respectively. Ninety per cent of women in the study group were delivered within 10 hours of active labour. Babies that weighed <=3kg were 45% and >3kg were 55%. The possibility of being high risk was twice more among those delivered by CS. However, it was not statistically significant (p value 0.077). Labour was induced in 38% patients. The Odds of Induction of Labour (IOL) were two times more and delivering at night was three times more amongst CS. The likelihood of labour exceeding 10 hours was four times (81%) if the patient had a CS. Moreover 48% of the babies weighing >3kg were delivered through CS. Maternal age, high risk pregnancies, gender of baby and epidural analgesia were not statistically significant predictors of mode of delivery (MOD) in this study. CONCLUSION: Induction of Labour, night time delivery, prolonged labour and birth weight <3kg were found to be associated with the increased CS rate among NTSV. Therefore further research is required in order to address these factors and to reduce the increasing Caesarean Section. PMID- 27182231 TI - Gaucher disease in Iraqi children (Clinical, diagnostic & therapeutic aspects). AB - BACKGROUND AND OBJECTIVE: Gaucher disease is the most common inherited lysosomal storage disorder. It is a multi organ disease affecting bone marrow, liver, spleen, lungs, and other organs contributes to pancytopenia and massive hepatosplenomegaly. This study aimed to spotlight on clinical and laboratory characteristics of children with Gaucher disease to raise awareness among physicians about the disease and to evaluate the outcome of enzyme replacement therapy (ERT). METHODS: Clinical courses were reviewed in 30 patients with age (2 22 years) with Gaucher disease. After starting (ERT), assessment of response included serial measurements of hematological parameters, spleen and liver sizes, symptoms and signs of bone disease, growth and severity scores were also evaluated. RESULTS: The most presenting age group was (1 - 5) years (60%). Abdominal distension was the most common presenting symptom, Splenomegaly presented in all of the patients. A significant response to ERT was observed, weight and height increased, both liver and spleen sizes decreased. Hemoglobin level normalizedin (67%) of the anemic patients, platelet count normalized in (53.8%)after 6 months from (ERT), the mean of severity scoring index decreased with ERT from (10.2+/-5.8) to (7.8+/-5.7) after one year of treatment. CONCLUSION: Using ERT was safe and effective in the reversal of hematological complications and organomegaly in most of the patients. PMID- 27182232 TI - PBL triggers in relation to students' generated learning issues and predetermined faculty objectives: Study in a Malaysian public university. AB - OBJECTIVES: Foundational elements of problem based learning (PBL) are triggers, tutors and students. Ineffective triggers are important issues for students' inability to generate appropriate learning issues. The objective of this study was to evaluate PBL triggers and to determine similarities of students' generated learning issues with predetermined faculty objectives. METHODS: It was a retrospective study conducted in 2014 analyzing all 24 PBL-triggers used at Centre for Foundation Studies, International Islamic University Malaysia, in four semesters during two consecutive years 2011 and 2012. Triggers were used as textual and illustration format equally in each semester. Total 16 PBL-triggers with highest and lowest achieving similarities of learning issues with predetermined faculty objectives were selected equally from each semester and format. The trigger quality and learning issues related to predetermine faculty objectives were analyzed and presented as mean and percent distribution. RESULTS: Mean similarities score of students' generated learning issues were 3.4 over 5 predetermined faculty objectives which was 68%, varied from 58% to 79%. More than 70% similarities were generated from five textual and four illustrated triggers, while <70% similarities observed from four illustrated and three textual triggers. CONCLUSION: Whatever the trigger formats in PBL, it is the designing considering influential variables that influence higher outcomes. Triggers should have planned clues that lead students to generate issues correlate with faculty objectives. Educational institution should emphasize on training needs of faculty at regular interval to develop and re-in force teachers' skills in trigger design, thereby to promote a sustainable educational and organizational development. PMID- 27182233 TI - Is open decortication superior to fibrinolytic therapy as a first line treatment in the management of pleural empyema? AB - OBJECTIVE: To confirm that either Fibrinolytic therapy or open decortication which of the two is an effective First line treatment of pleural empyema. METHODS: This prospective comparative study was conducted in the department of surgery Sheikh Zayed Medical College and Hospital, Rahim Yaar Khan. Seventy eight (78) patients were included in this study. There were two groups of patients; Group I (n=35) patients treated with fibrinolytic therapy, Group II (n=43) patients treated with open decortication. Data was entered and analyzed in SPSS v16. Student's t-test was used for comparison of quantitative variables. Chi square and Fisher's Exact test were used for comparison of qualitative variables. P-value <= 0.05 was taken as significant difference. RESULTS: There was no significant difference in base baseline characteristics of patients of Group I and II. Incidence of comorbidities was also same between the groups. Most of the patients in Group I and II were in empyema stage III. Fluid cultures was positive in 33 (94.3%) patients in group I and 39 (90.7%) patients in group II. 30 (85.7%) was successfully treated using fibrinolytic therapy but this therapy failed in five (14.3%) patients, two of these patients expired within the hospital. There was only one (2.3%) treatment failure in open decortication Group that patient expired within the hospital (p-value 0.04). Overall duration of hospitalization was significantly high in fibrinolytic group, this was 17.6+/- 1.95 days versus 12.09+/- 2.18 days in open decortication group (p-value<0.0001). There was no significant difference regarding operative mortality within the two groups. CONCLUSION: Open Drainage is associated with better outcomes as compared to fibrinolytic therapy when used as a First line treatment of empyema. PMID- 27182234 TI - Clinical effect of treating renal transplant recipients with percutaneous coronary intervention and its safety. AB - OBJECTIVE: To explore clinical effect of treating acute coronary syndrome (ACS) of renal transplant recipients with percutaneous coronary intervention and its safety. METHODS: Forty two renal transplant recipients who were diagnosed with acute coronary syndrome and received percutaneous coronary intervention (PCI) in our hospital were selected. Serum creatinine (Cr) and glomerular filtration rate (GFR) were compared before surgery, 48 ~ 72 hour after surgery and one year after surgery. All patients were followed up. RESULTS: All patients successfully completed PCI. Contrast-induced nephropathy was not found after surgery. Cr and GFR 48 ~ 72 hour after surgery and one year after surgery had no significant differences with that before surgery (P>0.05). The follow up lasted for (61.2+/ 32.2) months averagely. Of 42 cases, 4 cases died, 6 cases were found with nonfatal myocardial infarction, 4 cases were observed with repeat revascularization and 12 cases had accumulative major adverse cardiovascular events (MACE). CONCLUSION: PCI is proved to be effective in treating renal transplant recipients; no severe complications are found and renal function recovers well after treatment. PMID- 27182235 TI - Clinical predictors of anticipatory emesis in patients treated with chemotherapy at a tertiary care cancer hospital. AB - OBJECTIVE: To determine the clinical predictors of anticipatory emesis in patients treated with chemotherapy at a tertiary care cancer hospital. METHODS: This was a cross-sectional study conducted on 200 patients undergoing first line chemotherapy with minimum of two cycles at inpatient department and chemotherapy bay of Shaukat Khanum Memorial Cancer Hospital and Research Centre Pakistan. Anticipatory nausea and vomiting develops before administration of chemotherapy. Clinical signs and symptoms in patients with or without anticipatory emesis were compared using chi square test statistics. RESULTS: The mean age of the study participants was 36.68 years (SD+/-12.23). The mean numbers of chemotherapy cycles administered were 3.23 (SD+/-1.2). Chemotherapy related nausea and vomiting was experienced by 188 (94%) patients and anticipatory nausea vomiting was reported in 90 (45%) of patients. Greater proportions of patients with anticipatory emesis were females. Fourteen (15.5%) p-value=0.031 patients with anticipatory emesis had history of anxiety and depression. Fifty nine (65.5%) p value =< 0.0001 patients with anticipatory emesis had severe nausea after last chemotherapy cycle. Forty six (51.11%) p=<0.0001 patients had motion sickness. CONCLUSION: Female gender, history of motion sickness, anxiety and depression, severe nausea and vomiting experienced in pervious cycle of chemotherapy were clinical predictors of anticipatory nausea and vomiting. PMID- 27182237 TI - Plastibell Device Circumcision versus Bone Cutter Technique in terms of Operative Outcomes and Parent's Satisfaction. AB - OBJECTIVE: To compare the rate of complications of Plastibell and bone cutter circumcision technique and recognition of top worries and satisfaction rate in the mind of parents before and after the procedure of Plastibell device (PD) circumcision in infants less than 6 months of age. METHODS: It was a descriptive prospective study conducted at department of surgery Sheikh Zayed Hospital, Rahim Yar Khan. Two hundred parents of infants of less than six months of age were recruited for this study. Infants were divided into two equal groups. Group I included Plastibell circumcision technique and Group II included Bone Cutter Circumcision technique. Data was analyzed using SPSS Version 17. Independent sample t-test and chi-square test was used to compare quantitative and qualitative variables respectively. P-value <0.05 was taken as significant difference. RESULTS: Total number of two hundred infants were included in this study. Most common worries of parents about Plastibell Device circumcision were; fear of fever (42.0%). Fear of pain and bleeding (66.0%). Plastibell Device method was associated with less operation time and bleeding as compared to bone cutter method (P-value <0.0001 and <0.0001 respectively). Incidence of complications other than bleeding and infection was 3.0% in bone cutter method and 1.0% in Plastibell device method. Pain score was significantly less in plastibell device group (p-value <0.0001). Post-operatively, 98% parents showed complete procedural satisfaction in Plastibell group versus 87% parents in bone cutter one month after surgery (P-value 0.003). About 4% parents in bone cutter method group showed cosmetic displeasure versus only 1% parents in plastibell device group. CONCLUSION: The study concluded that Plastibell Device circumcision is a safer technique for circumcision and is associated with highest level of parent's satisfaction. PMID- 27182236 TI - Body mass index and other anthropometric variables in children with sickle cell anaemia. AB - OBJECTIVES: The objectives of this study were to determine the anthropometric variables of children with sickle cell anaemia and comparing it with those with normal haemoglobin genotype. METHODS: A cross sectional study of anthropometric measurements was conducted over a period of six months. Children with sickle cell anaemia in steady state aged between 6-20 years were recruited. Nutritional assessment was done using anthropometrical variables. Data were analyzed using the Statistical Package for Social Sciences program (SPSS), version 20. RESULTS: The sickle cell patients comprised of 20 males and 20 females. There were an equal number of controls with an equal male to female ratio of 1:1. Forty eight percent (19) of the children with sickle cell anemia were underweight (< 5th %ile) and this is statistically significant. chi(2)=18.02 and p=0.000. When compared with subjects with normal haemoglobin genotype only five of them (13%) were underweight. chi(2)=10.286 and p=0.001. The controls weighed significantly more than the HbSS patients and also had significantly larger body surface compared to the HbSS population (P<0.05). CONCLUSION: BMI and other anthropometric variables among children with sickle cell anemia were low when compared with children with normal Haemoglobin genotype. PMID- 27182238 TI - Students' perspective of bedside teaching: A qualitative study. AB - OBJECTIVES: To determine students' perception of bedside teaching, to find out barriers in its effective implementation and to suggest strategies to make it an effective learning tool. METHODS: This study was conducted in Faculty of Medicine, Northern Border University Arar, Kingdom of Saudi Arabia between November 2013 and January 2014. The study design was qualitative inductive thematic analysis using transcripts from audio-recorded focus group discussions. Four focused group discussions with medical students of 4(th) and 5(th) year MBBS were conducted. Each 40 to 50 minutes discussion session was audio taped and transcribed verbatim. Thematic analysis extracted key themes pertaining to objectives of the study. RESULTS: A total 75 students of 4(th) and 5(th) year MBBS took part in the study, 48 were female and 27 of them were male. Students believed that bedside teaching is valuable for learning essential clinical skills. They described many barriers in its effective implementation: uncooperative and less number of patients and faculty attitude. Our students suggested various strategies to address these barriers: promotion of awareness among general public about students' learning and its benefits, free medical treatment for expatriates and building of university hospital. CONCLUSION: Bedside teaching is an important learning tool. Its utility can be enhanced by orienting local patients' attitude towards importance of students' learning, by providing free medical treatment to expatriates and by including bedside teaching in faculty development programs. PMID- 27182239 TI - Yield of closed pleural biopsy and cytology in exudative pleural effusion. AB - OBJECTIVE: To determine diagnostic yield of Closed Pleural Biopsy (CPB) and Cytology in Exudative Pleural Effusion (PE). METHODS: This prospective comparative study was conducted at Chest Unit-II & Medical Unit-IV of Dow University of Health Sciences, Karachi Pakistan from January 2011 till December 2014. RESULTS: Ninety-four patients with exudative PE were finally included. The mean age (SD) was 44.0 (13.8) years. Overall Specific Diagnosis was reached in 76/94 patients; 46 Tuberculosis PE (TPE) & 30 Malignant PE (MPE). CPB diagnosed all TPE patients alone and 28/30 of MPE. Cytology diagnosed only 10/30 patients of MPE with 8 patients having both CPB & Cytology positive for malignancy whereas in the remaining two cases only Cytology positive. The sensitivity of CPB in detecting TPE and MPE was 93.9% and 82.4% respectively whereas specificity for both was 100%. The diagnostic yield of cytology in detecting MPE is only (33.3%). The diagnostic yield of CPB for TPE and MPE is 100% and 93.3% respectively. The overall specific diagnostic yield of CPB is 78.7%. CONCLUSION: CPB is better than pleural fluid cytology alone with the later adding little to diagnostic yield when both combined in distinguishing TPE from MPE, the two main differential of exudative PE in a TB-Endemic country. PMID- 27182240 TI - Educational resources used by medical students in primary healthcare rotation: A cross sectional study. AB - OBJECTIVE: To identify what educational resources are used by medical students for their personal study during Primary health care (PHC) clinical rotation and the reasons for making these choices at King Saud University in Riyadh, Saudi Arabia. METHODS: A survey of 176 male and female medical students was conducted during PHC rotation. A self-administered questionnaire ascertained the type of educational source with reason and preferred type of teaching method. Responses by male and female students were compared by using Pearson's Chi-square tests. RESULTS: Of the 176 students, 85.8% used handouts, 77.3% used the internet, and 46.6% used textbooks. Of the three types of resources, 14.8% used one, 31.8% used all three sources, and 53.4% used two sources. Reasons for selecting a resource were; educational materials are up to the point (88.6%), convenient (85.2%), reliable (77.3%) fit the learning style (77.3%), exam focus (60.8%), recommended by seniors (57.4%), recommended by department (56.8%). The preferred teaching method was lecture (79.5%), and least preferred was student presentations (55.1%). Female medical students used internet related material greater than the males (86.9% versus 68.5%; p value <0.001), and tended to utilize more than one educational resource than male students. CONCLUSION: Medical students used multiple resources for relevance and convenience. Female students used network resources more than male students. PMID- 27182241 TI - Ankylosing Spondylitis: A rheumatology clinic experience. AB - OBJECTIVE: To determine the frequency, demographics, laboratory and radiological features in patients with Ankylosing Spondylitis. METHODS: This is a retrospective analysis of prospectively collected data of patients with a diagnosis of Ankylosing Spondylitis (AS), based on Modified New York criteria. The study was conducted at the Rheumatology Clinic of Jinnah Postgraduate Medical Centre (JPMC), from February 2004 to February 2014. Detailed history, examination and laboratory investigations were recorded in a pre-designed structured proforma. The frequency, demographic characteristics, extra-articular features and associated co-morbidities were studied. RESULTS: A total of 603 patients were registered in our Rheumatology Clinic during this period, with a definitive diagnosis of inflammatory rheumatological disorders. Out of these, Ankylosing Spondylitis (AS) was diagnosed in 32 (5.3%) patients. 24 were male and 8 patients were female. The commonest affected age group was between 21-40 years. Majority of the patients belonged to Pathan ethnicity. CONCLUSION: The demographic features of AS are same as reported in earlier studies from other parts of the world. The predominance of AS in specific ethnic groups is a fact that needs to be studied. Larger studies are required for clarifying the triggers of this disease. It often leads to severe disability, hence an early diagnosis and prompt treatment is required for better disease control and quality of life. PMID- 27182242 TI - Influence of different anesthetic and analgesic methods on early cognitive function of elderly patients receiving non-cardiac surgery. AB - OBJECTIVE: To discuss over influence of two different anesthetic and analgesic methods on early cognitive function of elderly patients who received non-cardiac surgery. METHODS: Two hundred and six elderly patients who underwent non-cardiac surgery were selected as research subjects. They were randomly divided into observation group (103 cases) and control group (103 cases). Patients in observation group were given combined spinal and epidural anesthesia and epidural analgesia, while patients in control group adopted general anesthesia and intravenous analgesia. Neurological function test was carried out one day before surgery and on the 7(th) day after surgery. Moreover, changes of postoperative pain degree, neuropsychological function and cognitive function were observed and compared. RESULTS: On the 7(th) day after surgery, incidence of cognition impairment in observation group and control group was 48.50% (50/103 cases) and 44.70% (46/103 cases), and difference between groups had no statistical significance. Visual Analogue Scale (VAS) Score of observation group was much lower than control group in the 12(th), 24(th) and 48(th) h after surgery (p < 0.05). Logistic regression analysis suggested that, short education years and general surgery were independent risk factors for early cognition impairment. CONCLUSION: About 46.60% elderly patients undergoing non-cardiac surgery developed cognition impairment, but influence of different anesthetic and analgesic methods on incidence of postoperative cognition impairment of elderly patients had no significant difference. PMID- 27182243 TI - Hepatitis-C virus infection among injecting drug users in Lahore, Pakistan: A cross sectional study. AB - OBJECTIVES: To determine the prevalence and risk factors of hepatitis C virus among injecting drugs users, furthermore different genotypes of HCV infection and their effect on viral load were also found and subsequently most prevalent subtype was predicted. METHODS: All samples were processed for Anti-HCV antibody detection through ELISA by using third generation ELISA Kit. The Anti-HCV positive serum samples were stored for RT-PCR to estimate the viral load and genotypes of HCV for study. Injecting drug users selected from in and around Lahore Metropolitan from July 2012 to August 2013 was included. The data analysis was completed by using SPSS version 16. A p-value of < 0.05 was considered to be significant. RESULTS: A total of 241 Injecting drug users were enrolled and screened for Anti HCV in the study. Prevalence of HCV infection in IDUs from Lahore was found to be 36.09%. Education (p=0.000), low socioeconomic status (p=0.011), Blood transfusion (0.003), any tattoo on the body (p=0.002), use of injectable drugs with reused syringes (p=0.000) and sharing of syringes (p=0.001) in groups was significantly associated with HCV infection. Some utensils were also significantly associated with HCV status. The most common subtype of HCV genotype was 3a (n=65) followed by 2a (n=15) and 1a (n=6). CONCLUSION: The study reveals that IDUs with reused syringes status and sharing of syringes in group had more chances to get HCV infection. The viral load in IDUs infected with different subtypes of genotype was significantly associated. PMID- 27182244 TI - The modified Dunn procedure for slipped capital femoral epiphysis does not reduce the length of the femoral neck. AB - OBJECTIVE: The treatment of slipped capital femoral epiphysis (SCFE) is evolving, with the development of new surgical techniques. |We wanted to study if modified Dunn procedure restores the normal alignment of the proximal femur and the risk of avascular necrosis is increased. METHODS: This is a single centre, retrospective study, comparing the outcomes of in situ pinning and modified Dunn procedure. Between 2001 and 2014, 7 children (7 hips) underwent the modified Dunn procedure and 10 children (10 hips) pinning in situ for stable and unstable SCFE. Mean age of the patients was 12.7 years with a median follow-up of 18 months. RESULTS: The radiological parameters improved in the modified Dunn procedure group, while the length of the femoral neck didn't change significantly (p=0.09). Postoperative clinical outcomes were slightly better in the modified Dunn procedure group (6 hips out of 7 had good and excellent results) compared to the pinning in situ group (8 good and excellent results out of 10 hips) (p=0.04). No avascular necrosis was found and there were no cases of chondrolysis. CONCLUSION: Radiographic parameters of the proximal femur assessed in our study improved in all hips that underwent modified Dunn procedure, without the creation of secondary deformities. PMID- 27182245 TI - Diagnostic Accuracy of Ultrasound B scan using 10 MHz linear probe in ocular trauma;results from a high burden country. AB - OBJECTIVE: To study the diagnostic accuracy of Ultrasound B scan using 10 MHz linear probe in ocular trauma. METHODS: A total of 61 patients with 63 ocular injuries were assessed during July 2013 to January 2014. All patients were referred to the department of Radiology from Emergency Room since adequate clinical assessment of the fundus was impossible because of the presence of opaque ocular media. Based on radiological diagnosis, the patients were provided treatment (surgical or medical). Clinical diagnosis was confirmed during surgical procedures or clinical follow-up. RESULTS: A total of 63 ocular injuries were examined in 61 patients. The overall sensitivity was 91.5%, Specificity was 98.87%, Positive predictive value was 87.62 and Negative predictive value was 99%. CONCLUSION: Ultrasound B-scan is a sensitive, non invasive and rapid way of assessing intraocular damage caused by blunt or penetrating eye injuries. PMID- 27182246 TI - Application value of magnetic resonance imaging in diagnosing central nervous system lymphoma. AB - OBJECTIVE: To describe the magnetic resonance imaging (MRI) appearance of central nervous system lymphoma. METHODS: We retrospectively reviewed MRI images of 40 patients who had pathologically proven primary central nervous system lymphoma (PCNSL) and received treatment in Binzhou People's Hospital, Shandong, China from January to December in 2014. Location, size and form of tumor was observed and relevant data were recorded for analysis. RESULTS: Foci of 40 cases of PCNSL all located in brain, among which. 18 cases were single (45.0%) and 22 cases were multiple (55.5%). Of 96 Foci, 84 were supratentorial, 12 were subtentorial. Enhanced MRI scanning showed that, most Foci had significant homogenous enhancement, shaping as multiple nodular or lumpy, and few had ring-enhancement. MRI suggested that, T1 signal of most Foci concentrated on low signal segment and T2 signal gathered on high signal segment, suggesting a significant homogeneous enhancement; moreover, mild and medium edema surrounded the tumor. They were pathologically confirmed as B cell derived non-hodgkin lymphoma. Except one case of Burkitt lymphoma, the others were all diffuse large B cell lymphoma which was observed with diffuse distribution of cancer cells (little cytoplasm, large nucleus, rough perichromatin granule) in same size. Fifteen cases were observed with sleeve-like infiltration of cancer cells around blood vessels. No case was found with hemorrhage, necrosis or calcification. CONCLUSION: Pathological foundation of PCNSL determines its characteristic MRI performance. Typical case of PCNSL can be diagnosed accurately by MRI. PMID- 27182247 TI - Hypovitaminosis-D: Frequency and association of clinical disease with biochemical levels in adult patients of RMI Medical OPD. AB - BACKGROUND AND OBJECTIVE: Vitamin D is steroid hormone essential for maintaining many important functions in the body. Hypovitaminosis D has become worldwide problem affecting all age groups and both genders, but its prevalence is very high in South Asia. Therefore this study was aimed to determine frequency of hypovitaminosis D in adult patients of RMI Medical Out Patients Department (OPD) and find association of clinical disease with biochemical levels. METHODS: It was a cross sectional study carried out on all patients visiting RMI Medical OPD from 1(st) Jan, 2015 to 30(th) April, 2015 with clinical indications using universal sampling technique involving 400 subjects. Data was analyzed using SPSS 16. RESULTS: Out of 400 subjects 85(21.3%) were males, 315(78.8%) were females, biochemical hydroxyvitamin-D3 deficiency was present in 320 (80%) subjects with 86(21.5%) having severe deficiency, 176(44%) having moderate deficiency and 58(14.5%) having mild deficiency. There was statistically significant association between biochemical deficiency and severity of clinical disease manifestation, calculated using chi square test. (p < 0.001). CONCLUSION: Most of the patient with musculoskeletal symptoms had vitamin D deficiency affecting all age groups and mostly female gender. There is a statistically significant association between low biochemical hydroxyvitamin-D3 levels and severity of clinical signs and symptoms which can provide evidence for replacement therapies in rural and far flung areas where biochemical assays are not available. Early recognition and replacement can prevent the massive complications, which deficiency of vitamin D makes us prone to develop. PMID- 27182248 TI - Measurements of bone mineral density and stiffness index in young Saudi females. AB - OBJECTIVE: To examine the ability to use Quantitative Ultrasonography (QUS) densitometer for screening of osteoporosis and osteopenia by comparing QUS values obtained at the calcaneus region to bone mineral density (BMD) values measured at the spine and the neck of the femur using Dual Energy X-ray Absorbemetry (DXA). METHODS: QUS (in the calcaneus region) and DXA (the spine and the neck of femur respectively) measurements were performed in 101 females. RESULTS: The precision of the QUS parameters varied from 1.77-1.78, whereas the reliability ranged from 92.2%-98.6%. For the QUS parameters variability between subjects was greater than that within subjects. Positive correlation were found between stiffness index (SI) and BMDspine and BMDN.femur (r= 0.29 & r=0.25 respectively, P < 0.05) and a strong positive correlation between T-scorecalcaneus and both T-scoreSpine and T scoreN.femur (r= 0.5 & r=0.58 respectively, P < 0.01). CONCLUSIONS: QUS is a reliable technique to be used in combination with DXA for the investigation of osteopenia and osteoporosis. PMID- 27182249 TI - Ameliorating effect of Allium Sativum on high-fat diet induced fatty liver in albino rats. AB - OBJECTIVE: To assess the hepatoprotective effect provided by fresh garlic on fatty liver induced by high-fat diet. METHODS: This experimental study was carried out at BMSI, JPMC from October to November 2008. Thirty adult albino rats, 200-240 gram weight, were divided into three groups. Group A received control diet, Group B received high-fat diet (20 mg butter/100 gm diet) and Group C received high-fat diet with fresh garlic (20 mg butter with 6 gm fresh garlic/100 gm diet). The groups were further divided on the basis of duration of treatment, four weeks and eight weeks respectively. The rats were sacrificed, liver removed, weighed and relative liver weight calculated. Hepatic tissue was processed and tissue slides stained with haematoxylin and eosin. RESULTS: There was significant increase in relative liver weight in group B animals as compared to the control animals, which decreased significantly in group C. Haematoxylin and eosin stained sections revealed ballooned hepatocytes having vesicular appearance with pyknotic nuclei in high-fat group which were preserved to a great extent in group C animals. CONCLUSION: This study has shown that use of fresh garlic along with high-fat diet prevents its damaging effects on liver to a great extent. PMID- 27182250 TI - Tea drinking habits and osteoporotic hip/femur fractures: A case-control study. AB - OBJECTIVE: To explore the relationship between tea drinking habits and osteoporotic hip/femur fractures. METHODS: Paired case-control method was used for face-to-face interviews from January 2010 to June 2014. Patients (n=435) with newly osteoporotic hip/femur fracture and 435 controls with the same gender and age (+/-3) were given questionnaire survey. The survey content included general situation, detailed tea drinking and other diet condition, health-related behavior and family history of fractures, etc. RESULTS: Single factor logistic analysis showed that the habit of drinking tea can significantly reduce the risk of hip/femur fracture. Cumulative year of tea drinking, the cumulative amount of tea and tea concentration (low dose group) have the maximum protection for fracture, while the high dose group is weaker in protection (trend test, P<0.05). After adjustment for age, energy, BMI, education degree, parents' history of fracture, second hand smoke exposure, calcium supplements, and equivalent energy consumption of physical activity, etc, the above association still showed significant linear trend, but the associated strength was slightly reduced. But stratified analysis found that the effect of tea drinking was only statistically significant in men. And there were no statistically significant differences of people with different education degree. CONCLUSIONS: Regular tea drinking can reduce the risk of osteoporotic hip/femur fractures in middle-aged and elderly men. PMID- 27182251 TI - Adherence to Methotrexate therapy in Rheumatoid Arthritis. AB - OBJECTIVE: To determine adherence to methotrexate (MTX) therapy in patients with Rheumatoid Arthritis (RA) and to identify factors that promote either adherence or non adherence. METHODS: One hundred Rheumatoid Arthritis patients on MTX for at least two months were enrolled. Questionnaire was completed by direct interview. Details recorded were, demographics (age, sex, education, monthly income), disease duration, duration on MTX and current dose. Disease Activity Score on 28 joint counts (DAS 28) at the current visit, concomitant drugs taken and number of doses of MTX missed in the previous 8 weeks were noted. Non adherence was defined as omission of any three or more prescribed doses of MTX in previous 8 week. Patients were asked for the factors that motivated their adherence to MTX as well as factors for non adherence. Presence of side effects due to MTX was also recorded. RESULT: Non adherence was found among 23% of cases. Patients of low socioeconomic group (p <0.0001) and on MTX for longer duration (p <0.001) had higher non adherence. Non adherent patients had significantly higher disease activity as measured by DAS 28 (p<0.001). Good counseling and education by the doctor was a strong predictor of adherence (p <0.001). Lack of affordability (p <0.001); lack of availability at local pharmacy (p <0.001); lack of family support (p <0.001) and lack of awareness regarding need and importance of MTX (p < 0.001were found as significant factors for non adherence. CONCLUSION: MTX non adherence in RA is noted in about one fourth of study group. Various economical and social issues lead to non adherence but good patient education and counseling by doctor could promote adherence in this study group. PMID- 27182252 TI - Alanine aminotransferase as a predictor of adverse perinatal outcomes in women with intrahepatic cholestasis of pregnancy. AB - OBJECTIVE: To evaluate the associations between adverse perinatal outcomes and serum transaminase levels at the time of diagnosis in patients with intrahepatic cholestasis of pregnancy. METHODS: We performed a retrospective analysis of patients hospitalized for evaluation of intrahepatic cholestasis of pregnancy from January 2013 to June 2014 in a tertiary center. Seventy-one patients were divided into two groups according to the presence (Group I) or absence of adverse perinatal outcomes (Group II). RESULTS: The mean aminotransferase levels and conjugated bilirubin levels at the time of diagnosis were significantly higher in Group I than in Group II. Receiver operating characteristic curve analysis revealed that the alanine aminotransferase level could predict adverse perinatal outcomes with 76.47% sensitivity and 78.38% specificity, and the cut-off value was 95 IU/L. Among patients with intrahepatic cholestasis of pregnancy, those with adverse perinatal outcomes were significantly older, had an earlier diagnosis, and had higher alanine aminotransferase levels. Using the 95-IU/L cut off value, patients with intrahepatic cholestasis of pregnancy had a 3.54-fold increased risk for adverse perinatal outcomes. CONCLUSIONS: Patients with intrahepatic cholestasis of pregnancy and high alanineaminotransferase levels should be followed up for possible adverse perinatal outcomes. PMID- 27182253 TI - Frequency of neck and shoulder pain and use of adjustable computer workstation among bankers. AB - BACKGROUND & OBJECTIVE: Neck and shoulder are the most susceptible areas for developing musculoskeletal symptoms among computer users. The modifiable risk factors for these work related musculoskeletal disorders include physical office environment and psychosocial work related factors. Computer workstation layout had been shown to be an important physical aspect of work environment that influences the upper quadrant symptoms. Our objective was to find the frequency of neck and shoulder pain and use of adjustable computer workstation among bankers of Islamabad/Rawalpindi/Multan. METHODS: A cross sectional study was conducted and 120 participants were questioned. Purposive sampling technique was used in this study. Maastricht Upper Extremity Questionnaire (MUEQ) was remodeled and important questions were extracted from its detailed version. The tool was then validated by taking expert opinion. Frequencies and percentages were calculated for categorical variables. RESULTS: Pain in the neck during working hours was experienced by 71.67% of the respondents and 48.33% of the participants had experienced shoulder pain during working hours. Adjustable keyboards were used by 16.67% of respondents. Back care material was used by 40% bankers. Adjustable chairs were used by 95.83% of the participants. Only 3% of the bankers did not have chairs with adjustable heights. Chairs with adjustable armrests were used by 25% bankers. CONCLUSION: Neck and shoulder pain are common occurrences among bankers. Most of the components of workstations of bankers were adjustable but some of them still need attention. PMID- 27182254 TI - Effects of ischemic postconditioning on expressions of pentraxin-related protein 3 and neutrophil CD11b in the plasma of patients with acute myocardial infarction after percutaneous coronary intervention. AB - OBJECTIVE: To evaluate the effects of ischemic postconditioning on expressions of pentraxin-related protein 3 (PTX3) and neutrophil CD11b in the plasma of patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI). METHODS: Fifty-six patients who had AMI with ST-segment elevation were randomly divided into a control group and an ischemic postconditioning group (n=28). Both groups received emergency PCI. After recanalization of infarct related arteries, the control group did not receive intervention within three minutes, while the ischemic postconditioning group was treated by low-pressure filling and emptying of balloon within one minute. The plasma expressions of PTX3 before and 24 hour after PCI were detected by ELISA, and those of neutrophil CD11b were detected by flow cytometry. RESULTS: PTX3 and neutrophil CD11b expressions of the two groups were similar before PCI, but those of the ischemic postconditioning group significantly decreased 24 hour after PCI (P<0.05). CONCLUSION: Ischemic postconditioning lowered the expressions of PTX3 and neutrophil CD11b in AMI patients after PCI, inhibited inflammatory response, reduced the adhesion between leukocytes and endothelial cells, and protected the ischemic-reperfused myocardium. PMID- 27182255 TI - Psychosocial implications of blindness and low vision in students of a school for children with blindness. AB - OBJECTIVE: To find out the psychosocial implications of blindness and low vision in students of blind school Bahawalpur. METHODS: A cross sectional descriptive study was carried out in Higher Secondary School for blind, Bahawalpur after getting approval from Institutional review board of Quaid-e-Azam Medical College, Bahawalpur and Principal of Blind School, Bahawalpur. Forty willing students filled a customized questionnaire, consisting of questions about logistic variables and questions regarding areas of satisfaction. Statistical analysis was performed using SPSS version 18. RESULTS: Out of 40, 55% (22/40) of them were found depressed (as assessed through DSM-lV), 50% (20/40) were having difficulty in making new contact but 52.5% (21/40) were satisfied with family care. CONCLUSION: Sixty percent (24/40) of blind school children experienced difficulty in their life. This study showed that blindness or low vision does have psychological implications like feeling of guilt, anxiety, sadness & depression. PMID- 27182256 TI - Clinical significance of quantitative and qualitative detection of BK and JC virus in blood and urine of renal transplantation recipients. AB - OBJECTIVE: To evaluate value of quantitative and qualitative detection of BK virus (BKV) and JC virus (JCV) in timely diagnosing polyomavirus-associated nephropathy (PVAN) occurring inrenal transplantation recipients. METHODS: We collected 306 cases of urine specimen and 310 cases of blood specimen from 306 patients who underwent renal transplant. Levels of BKV and JCV in blood and urine were detected using real-time quantitative polymerase chain reaction (PCR). RESULTS: Detection rate of BKV DNA was 33.3% (102/306) in urine and 34.8% (108/310); while that of JCV DNA was 30.7% (94/306) and 33.5% (104/310) respectively. The lowest detectable limit of BCK and JCV detection for patients who underwent renal transplant was 2*10(3) copies/ml, suggesting high specificity and sensitivity. CONCLUSION: Real-time quantitative PCR is able to monitor BCV and JCV in renal transplant recipients in a convenient and rapid way, thus it is beneficial for early discovery, diagnosis and treatment of PVAN. PMID- 27182257 TI - Corneal approach 20 Guage vitrectomy system for the management of congenital cataract. AB - OBJECTIVE: To evaluate the efficacy and complications of 20 gauge vitrectomy via corneal approach for the management of congenital cataract. METHOD: We performed anterior capsular vitreorhexis, lens matter aspiration (LMA), primary posterior vitrectorhexis and anterior vitrectomy via corneal approach using 20 gauge vitrectomy system in children younger than two years of age with congenital cataract between January 2014 to December 2014. The intra and postoperative complications were observed. RESULTS: Twenty nine eyes of 21 children were included in this study. Congenital cataract surgery using 20 gauge vitrectomy system via corneal approach did not reveal any intra operative complication. Post operatively all children were able to freely open their operated eyes. Conjunctival congestion at the incision site in four eyes and mild anterior chamber reaction in 8 eyes were seen on 1(st) daywhich resolved at one week follow up. Other major post operative complications such as inflammatory membrane, irregular pupil, posterior/anterior syneache and opacification of visual axis were not seen during follow up period. CONCLUSION: The 20-gauge vitrectomy system via corneal approach is easy to perform, is less time consuming, safe and effective for the management of congenital cataract in younger children. PMID- 27182258 TI - Application of multiplex PCR for Rapid and sensitive detection of human papillomaviruses in cervical cancer. AB - OBJECTIVES: Reffering to an increase in cervical cancer in the recent years, rapid, sensitive and economical detection of human papillomaviruses (HPVs) as causative agents of cervical cancer is important. The traditional methods for the detection of HPVs in cervical cancer, such as pap smear, suffer from limitation and PCR has a potential to overcome the limitaitons. The purpose of present research work was to identify the five important strains of HPV (16, 18, 31, 33 and 45) simultaneously by Multiplex PCR application. METHODS: Study was done on 100 cervical lesions of women. DNA was extracted from specimens by a genomic DNA purification kit. A 5-plex PCR was developed for the simultaneous detection of major HPV. Five pair of new primers was designed for detection of HPV 16, 18, 31, 33 and 45 by Multiplex PCR. RESULTS: Among the 100 evaluated samples, 82 were found positive to HPVs. In the meantime the highest rate of infection was for HPV 16. Also 30 of HPV positive samples had infections with two or more HPV types. CONCLUSION: Multiplex PCR assay used in present study can provide a rapid, sensitive and economical method for detection of viral infections and is applicable to small volumes of vaginal samples. PMID- 27182259 TI - Sentinel lymph node identification by blue dye in patients with breast carcinoma. AB - OBJECTIVE: To determine the diagnostic accuracy of methylene blue dye to detect axillary lymph node metastases in patients with breast carcinoma by taking histopathology as gold standard. METHODS: This quasi experimental study was done at Department of Surgery of Dow University Hospital Karachi during January 2013 to September 2015 after the approval of Hospital Ethical Committee. A total number of 85 patients with biopsy proven carcinoma were included in the study.1% methylene blue dye was infiltrated in the peri tumoural area of the diseased breast. The blue stained node called sentinel lymph node (SLN) was recognized and carefully dissected out. SLN and mastectomy with axillary clearance specimen was sent for histopathology in two separate bottles and the report of the histopathology was compared. RESULTS: The axillary lymph nodes were positive for carcinoma in 61 cases out of 85(71.7%). Two of the patients had negative sentinel lymph node but positive non sentinel lymph node (false negative), and in three cases sentinel lymph node were involved only but not the rest of the axilla (False positive). The sensitivity, specificity and accuracy were 96.8%,86.36% and 94.1% respectively. CONCLUSION: Methylene blue dye technique is a reliable and safe diagnostic modality for detection of Sentinel lymph node in breast cancer patient because of its high accuracy. PMID- 27182260 TI - Prevalence of dental caries and associated social risk factors among preschool children in Riyadh, Saudi Arabia. AB - OBJECTIVES: To determine the prevalence of dental caries, and associated social risk factors among preschool children in Riyadh, Saudi Arabia. METHODS: The study consisted of a random sample of 3 to 5 years- old preschool children who were examined in Riyadh, Saudi Arabia; 388 children (184 boys and 204 girls) were examined from 10 different preschools. Each surface of their teeth was examined for dental caries utilizing modified WHO criteria (WHO, 1997). Data information about age, gender and social factors status were obtained by questionnaires that had been answered by parents. RESULTS: About 69% of children had dental caries with dmft score of 3.4 (+/- 3.6) and dmfs of 6.9 (+/- 9.9). There was no statistically significant difference between boys and girls. Less caries was observed among children whose parents worked and it was statistically significant as well as whose mothers had high or low educational level. Increased number of family members appeared to have a high incidence of dental caries which was also statistically significant. There was no significant difference in dental caries prevalence with birth order. CONCLUSIONS: Dental caries among preschool children in Saudi Arabia was still very common. Improvement of preventive measure at early age should be emphasized by parents and dental health professionals. More attention is required for Non-working parents telling them about the risk of dental caries affecting their children and the awareness of preventive care of dental health. PMID- 27182262 TI - Clinical efficacy of tiotropium in children with asthma. AB - OBJECTIVE: To investigate the clinical efficacy of tiotropium in children with asthma. METHODS: Eighty children with newly diagnosed moderate persistent asthma were enrolled into this study. The children were randomly assigned to the fluticasone propionate aerosol group or the fluticasone propionate aerosol plus tiotropium group for 12 weeks. RESULTS: Lung function was significantly improved in both groups at 4, 8, and 12 weeks compared with baseline (P < 0.01). Moreover, lung function was significantly improved in the tiotropium group compared with the control group (P < 0.05). However, there was no significant difference in the incidence of severe asthma between the two groups (36.3% and 26.8%, respectively; P > 0.05). Compared with the control group, the number of days and frequency of short-acting beta2-adrenoceptor agonist use was significantly reduced in the tiotropium group (P < 0.05). Awakenings during the night were also significantly decreased (P < 0.00). There were no severe adverse reactions in either of the study groups. CONCLUSION: Tiotropium could significantly improve lung function, reduce the use of short-acting beta2-adrenoceptor agonists, and improve sleep in children with asthma. Furthermore, few adverse reactions were reported. PMID- 27182261 TI - Reliability of the universal goniometer for assessing active cervical range of motion in asymptomatic healthy persons. AB - OBJECTIVE: To determine within-rater and between-rater reliability of the universal goniometer (UG) for measuring active cervical range of motion (ACROM) in asymptomatic healthy subjects. METHODS: Nineteen healthy subjects were tested in an identical seated position. Two raters used UG to measure active cervical movements of flexion, extension, right side flexion, left side flexion, right rotation and left rotation. Each motion was measured twice by each of the two raters and was re-measured all over again after one week. Data analysis was performed using the intraclass correlation coefficient (ICC). RESULTS: The results demonstrated excellent within-session (ICC2,1 = 0.83 to 0.98) and between session (ICC2,2 = 0.79 to 0.97) intra-rater reliability and excellent inter-rater reliability (ICC2,2 = 0.79 to 0.92). CONCLUSION: Considering above results it is concluded that UG is a reliable tool for assessing ACROM in a clinical setting for healthy subjects. PMID- 27182263 TI - Otitis media with effusion: Accuracy of tympanometry in detecting fluid in the middle ears of children at myringotomies. AB - OBJECTIVE: (1) The diagnostic accuracy of tympanometry in detecting fluid in the middle ear space in children with otitis media with effusion by comparing its findings with those of myringotomies. (2) Identify the age group most commonly affected by OME. METHODS: This prospective study was conducted at the Department of ENT& Head and Neck Surgery, Postgraduate Medical Institute Hayatabad Medical complex, Peshawar from July 1, 2012 to April 30, 2015. Patients with suspicion of OME underwent tympanometry and later myringotomies. Using Jerger's classification, Type B tympanogram with normal canal volume was considered as conclusive evidence of fluid in the middle ear space. Its findings were compared with those of the respective myringotomies. From the data collected, the accuracy, sensitivity, specificity, positive predictive value and negative predictive values were calculated. RESULTS: A total 117 ears of 63 patients were operated. The age range was 3 to 12 years. The commonest age group (58.7%) affected by OME was 6-8 years. Type B tympanogram with flat curve and normal canal volume was obtained in 71.4% of the ears. Comparison with myringotomy findings showed TP 85, TN 13, FP 5 and FN 14. The diagnostic value of tympanometry was; Sensitivity 85.85%, Specificity 72.22%, PPV 94.44%, NPV 48.14% and Accuracy of 83.76%. P value calculated using chi square test showed that there was significant difference between tympanometry and myringotomy findings in OME (p < 0.05). CONCLUSIONS: OME is common in age group 6-8 years. Tympanogram Type B with normal canal volume is fairly sensitive in diagnosing this condition. However for occurrence of false positive results, final decision regarding management should be made on clinical findings and other supportive audiological tests. PMID- 27182264 TI - Use of a portable monitoring device (Somnocheck Micro) for the investigation and diagnosis of obstructive sleep apnoea in comparison with polysomnography. AB - OBJECTIVE: Polysomnography (PSG) remains the gold standard for the diagnosis of obstructive sleep apnoea syndrome (OSAS). While PSG is essential for OSAS, this technique is not suitable for epidemiological investigation due to its high cost. This study aimed to compare a portable monitoring device with PSG for the measurement of parameters related to the diagnosis of OSAS in rural areas. METHODS: We conducted a descriptive study of 155 patients (30 women and 125 men; mean age, 52+/-12years) who visited to the Hendek Government Hospital Sleep Laboratory between February 2011 and January 2013 Apnoea hypopnea index (AHI), mean levels of O2 (meanO2), desaturation index (DI), and minimum oxygen saturation (minO2) variations as measured using both PSG and a portable Somnocheck Micro (SM) device were compared. RESULTS: Differences were found between the meanO2 and DI, but not between AHI and minO2. Differences between the methods were not desired, but the relationship between the methods was distinct and supported our hypothesis. CONCLUSIONS: The results of our study have shown that the SM portable device can be used as an alternative diagnostic tool in this population either at home or in sleep clinic. PMID- 27182265 TI - McKenzie treatment versus mulligan sustained natural apophyseal glides for chronic mechanical low back pain. AB - BACKGROUND AND OBJECTIVE: Chronic mechanical low back pain is common among different age groups and genders. Different manual therapy techniques combined with exercise therapy and electrotherapy modalities play an important role in its management. Our objective was to compare the effects of McKenzie extension exercisesprogram (EEP) versus Mulligan Sustained Natural Apophyseal Glides (SNAGs) for chronic mechanical low back pain (CMLBP). METHODS: This randomized control trial (RCT) was conducted at Riphah Physical Rehabilitation Centre, Pakistan Railways General Hospital Rawalpindi, from 1(st) July to 31(st) December 2014. The inclusion criteria was patients of both gender and age range 30-70 years with minimum 4 weeks history of CMLBP. A total of 37 patients were screened out as per inclusion criteria and randomly placed into two groups. Twenty patients in group A were treated with Mulligan SNAGs and 17 patients in group B with McKenzie EEP for four weeks at two session per week and single session per day. Visual Analogue Scale (VAS), Oswestry Disability Scale (ODI) and lumber Range of Motion (ROM) were used as an assessment tools and were measured at baseline and at the completion 4 weeks intervention. The data was analyzed with SPSS to draw the statistical and clinical significance of both interventions. RESULTS: At the completion of 4 weeks intervention the pre and post statistical analysis revealed that clinically the McKenzie EEP improved pain (mean 9.12 to 1.46) and disability (73.82 to 6.24) slightly more than Mulligan SNAGs (pain: from 8.85 to 2.55, disability 73.75 to 7.05), while the Mulligan SNAGs improved lumbar ROM more effectively than McKenzie EEP in all directions including flexion, extension, side bending and rotation. Statistically there was no significant difference between the effects of two interventions in managing pain and disability, and improving Lumber ROM. CONCLUSION: McKenzie EEP is clinically slightly more effective in the management of pain and disability as compared with Mulligan SNAGs, while Mulligan SNAGs are more effective in the improvement of lumbar ROM as compared with Mechanize EEP in the management of CMLBP. PMID- 27182266 TI - Frequency of hypovitaminosis D and its associated risk factors in newly diagnosed pulmonary tuberculosis patients. AB - OBJECTIVE: To find out the frequency of hypovitaminosis D and its associated risk factors in newly diagnosed pulmonary tuberculosis patients prior to administration of standard anti tuberculosis therapy. METHODS: This cross sectional study was carried out in Ojha Institute of Chest Diseases-DUHS. After approval from BASR and following written informed consent eighty newly diagnosed, as per WHO criteria, tuberculosis patients were enrolled. Prior to the initiation of anti tuberculosis therapy, the serum vitamin D level was determined by 25-OH Vitamin D kit using the chemiluminescent immunoassay (CLIA) method. A cut off value of >30 ng/mL of serum vitamin D was taken as normal whereas a range between 10-30 ng/mL and <10 ng/mL were considered insufficient and deficient respectively. Frequency of socio-demographic associated risk factors of hypovitaminosis D was also determined. RESULTS: Out of eighty newly diagnosed tuberculosis patients 33 (41.25%) were males and 47(58.75%) were females with their ages ranging from 18-50 years. 54 patients (26 male and 28 female patients) were smokers. BMI of all the patients was found to be less than the normal ranges. Hypovitaminosis was present in all the cases. Vitamin D insufficiency was found in 49 participants (20 male and 29 female) whereas 31 patients (13 male and 18 female) were found to be vitamin D deficient. CONCLUSION: Prevalence of serum vitamin D level derangement is very high in newly diagnosed patients with pulmonary tuberculosis in our local setting which necessitates administration of adjuvant vitamin D along with standard anti tuberculosis therapy. PMID- 27182267 TI - Ego States of nurses working in psychiatric clinics according to transactional analysis theory. AB - OBJECTIVE: An effective interpersonal communication is an essential nursing skill required to help provide quality health care and meet the treatment objectives. The aim of this study was to investigate the communication between the psychiatric nurses and the patients in terms of Transactional Analysis Theory ego states. METHODS: The quantitative and qualitative research methods were used. The descriptive statistics (frequency, percentage, mean, standard deviation) were used in the data analysis and Kendall's Tau-c coefficient was used to assess the agreement among the observers. RESULTS: Of the psychiatric nurses, 66.7% (n = 14) had served as a psychiatric nurse for 1-10 years. Among the nurses, 52.4% (n=11) had received training about communication from any institution/organization. The agreement among the opinions of the nurses, the researcher and the charge nurses about the psychiatric nurses' ego states showed that there was a significant relationship between the researcher's opinion of the nurses' ego states and the charge nurses' opinion of the nurses' ego states in terms of Critical Parent, Nurturing Parent, Adult, Adapted Child and Natural Child ego states. CONCLUSION: It is suggested that training be offered in regards to raising awareness about ulterior transactions that can affect communication negatively, patient autonomy and therapeutic communication in particular, and patients requiring the use of special communication methods. PMID- 27182268 TI - Investigation of molecular heterogeneity of beta-thalassemia disorder in District Charsadda of Pakistan. AB - OBJECTIVE: Thalassemia is blood related disease which arises from the reduced level of hemoglobin in red blood cells (RBC), a protein responsible for carrying oxygen inside the body. Considering its widespread occurrence in developing countries like Pakistan, this study aims to investigate the common molecular anomalies of the beta thalassemia disease in district Charsadda, Khyber Pakhtunkhwa. METHODS: This work was done at Abdul Wali Khan University (AWKU) Mardan, Khyber Pakhtunkhwa, Pakistan. The work was performed on the blood samples collected from the patients and their families with beta thalassemia major (n = 13 families) belonged to District Charsadda. The collected blood samples were analyzed for presence of six known mutations with the help of polymerase cha in reaction technique i.e. amplification of refractory mutation system. RESULTS: Our Study reports six known mutations (IVS-1-5, FSC 8/9, CD 41/42, IVS-1-1, CD 15 and FSC-5) accounting for about 90% of total beta thalassemia genes in this country. Among the reported mutations, IVS 1-5 was the most prevalent beta thalassemia gene in patients belonging to District Charsadda. CONCLUSION: The results and findings of the current study may help in accessing the frequency of these common mutations and in initiating pre-natal diagnosis programme in Pakistan. PMID- 27182269 TI - Seroprevalence of acute dengue in a Malaysian tertiary medical centre. AB - OBJECTIVES: The aims of this study were to determine the seroprevalence of acute dengue in Universiti Kebangsaan Malaysia (UKM) Medical Centre and its correlation with selected haematological and biochemical parameters. METHODS: This cross sectional study was conducted from January to June 2015. A patient was serologically diagnosed with acute dengue if the dengue virus IgG, IgM or NS-1 antigen was reactive. RESULTS: Out of 1,774 patients suspected to have acute dengue, 1,153 were serologically diagnosed with the infection, resulting in a seroprevalence of 64.9%. Dengue-positive patients had a lower mean platelet count (89 * 10(9)/L) compared to the dengue-negative patients (171 * 10(9)/L) (p<0.0001). The mean total white cell count was also lower in the dengue-positive cases (4.7 * 10(9)/L vs. 7.2 * 10(9)/L; p<0.0001). The mean haematocrit was higher in patients with acute dengue (42.5% vs. 40.0%; p<0.0001). Likewise, the serum alanine transaminase level was also higher in patients with acute dengue (108 U/L vs. 54 U/L; p<0.0001). CONCLUSIONS: Dengue is very prevalent in UKM Medical Centre as most patients suspected to have acute dengue had serological evidence of the infection. The platelet count was the single most likely parameter to be abnormal (i.e. low) in patients with acute dengue. PMID- 27182270 TI - Bisphosphonates can prevent recurrent hip fracture and reduce the mortality in osteoporotic patient with hip fracture: A meta-analysis. AB - OBJECTIVE: This meta-analysis was conducted to investigate the efficacy of bisphosphonates for preventing recurrent hip fracture and reducing the mortality of elderly patient with hip fracture. METHODS: The databases of Pubmed, Embase and Cochrane Library were searched. All randomized or prospective matched controlled trials that assessed the efficacy of bisphosphonate for elderly patients with hip fracture were included. Two researchers independently extracted data of the included articles and assessed the methodological quality which was assessed based on Jadad scoring system or Newcastle-Ottawa scale. The second hip fracture incidence, mortality and complications were compared between bisphosphonates and control groups. RESULTS: Four studies including 3088 patients were included. Results showed that there were significant difference of second hip fracture (P<0.05) and mortality (P<0.05) between bisphosphonates group and control group. While no significant intergroup difference were observed for all complications. CONCLUSIONS: Bisphosphonates can prevent subsequent hip fracture, reduce the mortality, and does not increase the overall complications in elderly patients with hip fracture. PMID- 27182271 TI - Diabetic Macular Edema. AB - Diabetic macular edema (DME), one the most prevalent causes of visual loss in industrialized countries, may be diagnosed at any stage of diabetic retinopathy. The diagnosis, treatment, and follow up of DME have become straightforward with recent developments in fundus imaging, such as optical coherence tomography. Laser photocoagulation, intravitreal injections, and pars plana vitrectomy surgery are the current treatment modalities; however, the positive effects of currently available intravitreally injected agents are temporary. At this point, further treatment choices are needed for a permanent effect. SOURCES OF DATA SELECTION: The articles published between 1985-2015 years on major databases were searched and most appropriate 40 papers were used to write this review article. PMID- 27182272 TI - Quality of life for chronic psychiatric illnesses and home care. AB - Nowadays, mental illnesses are gradually increasing and so does chronic psychiatric patients. As a result of this increase, chronic psychiatric disorders lead the burden of patients and their families. To reduce the burden of mental illnesses on individuals and their families, treatment and care are given including psychosocial, physiological and medical support and social services. To begin with, home care enables both the patient and his or her family to stay at their own houses and not to be bothered with residents or long-term, institutional-based nursing homes. In addition, the home care providers deliver services to the patient's at their own house. The other advantages of taking care at home is that it eases financial issues in terms of reducing the cost, reduces the patient's symptoms and improve the individual's quality of life (QoL). In addition to these, home care also minimizes the burden on outpatient services and provides help for the patient and the family in order to solve their problems and give support. Home care services help patients to get their freedom back and enhance the quality of their lives. Thus, it is necessary to procure and implement these services and supply both the patient and his or her family a high quality life. SOURCES OF DATA/ STUDY SELECTION: Literature review was done by using the keywords "home care, patient with chronic mental illness, quality of life, home care nursing" from the sources including PsychINFO, PsychARTICLES, MEDLINE, PubMED, EBSCOHOST and The COCHRANE LIBRARY in the time period of 2005- 2015. PMID- 27182273 TI - Delayed visual loss due to radiation retinopathy. AB - Radiation retinopathy remains a devastating cause of visual morbidity in patients undergoing radiation for globe, orbit, and head and neck malignancies. A 65-year old female was admitted with the complaint of low vision in the right eye for two months. Best corrected visual acuity was 20/32 in the right eye and 20/25 in the left eye. Slit lamp examination was normal in both eyes. Fundoscopic examination revealed perifoveolar hard exudates, paramacular microhemorrhages, telangiectasias, and macular degeneration in both eyes. Fundus florescein angiography showed enlargement of the foveal avascular zone, perifoveal capillary telangiectasia, and widespread venous beading bilaterally. Optical coherence tomography revealed bilateral cystoid macular edema. The prediagnosis of diabetic retinopathy was not confirmed because of the absence of diabetes mellitus after endocrinologic evaluation. Detailed medical history explored external beam radiotherapy to the head and neck region for nasopharyngeal cancer 10 years ago. The ultimate diagnosis was radiation retinopathy. PMID- 27182274 TI - Phenotypic manifestation of congenital transverse amputation of autopod in Pakistani subjects. AB - Terminal transverse deficiency of forearm is a very rare limb malformation. Most of the cases have traumatic etiology and congenital presentation is less common. A series of six individuals with transverse deficiency through the hands is presented in this communication. The cases were congenital, morphologically similar and showed loss of four fingers, most often postaxial. The affected arm was reduced in size compared to the contralateral limb and there was distortion of palmer creases. All cases were sporadic and non-syndromic in nature. The characteristics of these cases were concordant with the symbrachydactyly type III or monodactylous type, when classified according to the scheme proposed by Blauth and Gekeler (1973). The malformation resulted in permanent quality-of-life impairment in these subjects and warrant prosthetic management. Detailed physical and phenotypic features of the patients have been presented. PMID- 27182276 TI - Hybridization in geese: a review. AB - The high incidence of hybridization in waterfowl (ducks, geese and swans) makes this bird group an excellent study system to answer questions related to the evolution and maintenance of species boundaries. However, knowledge on waterfowl hybridization is biased towards ducks, with a large knowledge gap in geese. In this review, we assemble the available information on hybrid geese by focusing on three main themes: (1) incidence and frequency, (2) behavioural mechanisms leading to hybridization, and (3) hybrid fertility. Hybridization in geese is common on a species-level, but rare on a per-individual level. An overview of the different behavioural mechanisms indicates that forced extra-pair copulations and interspecific nest parasisitm can both lead to hybridization. Other sources of hybrids include hybridization in captivity and vagrant geese, which may both lead to a scarcity of conspecifics. The different mechanisms are not mutually exclusive and it is currently not possible to discriminate between the different mechanisms without quantitative data. Most hybrid geese are fertile; only in crosses between distantly related species do female hybrids become sterile. This fertility pattern, which is in line with Haldane's Rule, may facilitate interspecific gene flow between closely related species. The knowledge on hybrid geese should be used, in combination with the information available on hybridization in ducks, to study the process of avian speciation. PMID- 27182278 TI - Advances in thermometry. AB - The last 25 years have seen tremendous progress in thermometry in the moderate temperature range (1 K to 1235 K). Various primary thermometers - based on different physics -have uncovered errors in the International Temperature Scale of 1990 and set the stage for the planned redefinition of the kelvin. PMID- 27182277 TI - Impact of flavonoid-rich black tea and beetroot juice on postprandial peripheral vascular resistance and glucose homeostasis in obese, insulin-resistant men: a randomized controlled trial. AB - BACKGROUND: Insulin-stimulated muscle blood flow facilitates plasma glucose disposal after a meal, a mechanism that is impaired in obese, insulin-resistant volunteers. Nitrate- or flavonoid-rich products, through their proposed effects on nitric oxide, may improve postprandial blood flow and, subsequently, glucose disposal. To investigate whether a single dose of nitrate-rich beetroot juice or flavonoid-rich black tea lowers postprandial muscle vascular resistance in obese volunteers and alters postprandial glucose or insulin concentrations. METHOD: In a randomised, controlled, cross-over study, 16 obese, insulin-resistant males consumed 75 g glucose, which was combined with 100 ml black tea, beetroot juice or control (water). Peripheral vascular resistance (VR), calculated as mean arterial pressure divided by blood flow, was assessed in the arm and leg conduit arteries, resistance arteries and muscle microcirculation across 3 h (every 30 min) after the oral glucose load. RESULTS: During control, we found no postprandial response in VR in conduit, resistance and microvessels (all P > 0.05). Black tea decreased VR compared to control in conduit, resistance and microvessels (all P < 0.05). Beetroot juice decreased postprandial VR in resistance vessels, but not in conduit artery and microvessels. Although postprandial glucose response was similar after all interventions, postprandial insulin response was attenuated by ~29 % after tea (P < 0.0005), but not beetroot juice. CONCLUSIONS: A single dose of black tea decreased peripheral VR across upper and lower limbs after a glucose load which was accompanied by a lower insulin response. Future studies in insulin-resistant subjects are warranted to confirm the observed effects and to explore whether long-term regular tea consumption affects glucose homeostasis. TRIAL REGISTRATION: The study was registered at clinicaltrials.gov on 30(th) November 2012 (NCT01746329). PMID- 27182279 TI - Cardiovascular risk factors among industrial workers: a cross-sectional study from eastern Nepal. AB - BACKGROUND: Cardiovascular diseases (CVD) are the number one cause of death globally, more people die annually from CVDs than from any other cause. An estimated 17.5 million people died from CVD in 2012, representing 46.2 % of all NCD death globally. An accurate characteristic of the cardiovascular risk factors in a specified population group is essential for the implementation of educational campaign. However, there are no reliable CVD risk factors burden, nor of its awareness and treatment status in Nepal industrial settings. We aimed to assess cardiovascular risk factors among men age 20-59 years in one of the largest industrial corridor of Eastern Nepal. METHODS: A total of 494 industrial workers between ages of 20-59 years, from two industries participated in the study. Pretested semi-structured questionnaire was used to collect the information. Primary outcome was cardiovascular risk factors based on STEPS survey and study on non-communicable disease in Nepal. A semi-structured questionnaire was used to interview 494 industrial workers. Lipid profile and serum blood glucose of 406 workers and electrocardiogram of 400 workers was done. RESULTS: The prevalence of cardiovascular disease (CVD) was 13.8 %. Those who were >45 years were 2.72 times more likely to develop CVD. Those who smoked more pack year, had family history of hypertension (HTN) and consumed no fruits were 4.32, 1.90.2.47 times more likely to develop CVD. Low density Lipoprotein (LDL) level <130 was found to be protective compared to LDL level above >= 130. On adjusted analysis those who did not consume fruits and had high LDL level were 3.32 and 3.03 more likely to develop CVD. CONCLUSION: There is high prevalence of CVD risk factors. Although majority of them are literate there is lack of health education and awareness among young male population in an eastern Nepal industrial setting. PMID- 27182275 TI - Integrated therapy for HIV and tuberculosis. AB - Tuberculosis (TB) has been the most common opportunistic infection and cause of mortality among HIV-infected patients, especially in resource-limited countries. Clinical manifestations of TB vary and depend on the degree of immunodeficiency. Sputum microscopy and culture with drug-susceptibility testing are recommended as a standard method for diagnosing active TB. TB-related mortality in HIV-infected patients is high especially during the first few months of treatment. Integrated therapy of both HIV and TB is feasible and efficient to control the diseases and yield better survival. Randomized clinical trials have shown that early initiation of antiretroviral therapy (ART) improves survival of HIV-infected patients with TB. A delay in initiating ART is common among patients referred from TB to HIV separate clinics and this delay may be associated with increased mortality risk. Integration of care for both HIV and TB using a single facility and a single healthcare provider to deliver care for both diseases is a successful model. For TB treatment, HIV-infected patients should receive at least the same regimens and duration of TB treatment as HIV-uninfected patients. Currently, a 2-month initial intensive phase of isoniazid, rifampin, pyrazinamide, and ethambutol, followed by 4 months of continuation phase of isoniazid and rifampin is considered as the standard treatment of drug susceptible TB. ART should be initiated in all HIV-infected patients with TB, irrespective of CD4 cell count. The optimal timing to initiate ART is within the first 8 weeks of starting antituberculous treatment and within the first 2 weeks for patients who have CD4 cell counts <50 cells/mm(3). Non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART remains a first-line regimen for HIV infected patients with TB in resource-limited settings. Although a standard dose of both efavirenz and nevirapine can be used, efavirenz is preferred because of more favorable treatment outcomes. In the settings where raltegravir is accessible, doubling the dose to 800 mg twice daily is recommended. Adverse reactions to either antituberculous or antiretroviral drugs, as well as immune reconstitution inflammatory syndrome, are common in patients receiving integrated therapy. Early recognition and appropriate management of these consequences can reinforce the successful integrated therapy in HIV-infected patients with TB. PMID- 27182280 TI - Breastfeeding practices on postnatal wards in urban and rural areas of the Deyang region, Sichuan province of China. AB - BACKGROUND: Despite the efforts that have been made to promote breastfeeding in China since the 1990s, there is still a very low prevalence of exclusive breastfeeding. The objective of this study was to assess the current situation of infant feeding practices during the postpartum hospital stay in urban and rural areas of the Deyang region. METHODS: Cross-sectional sampling was used in two urban hospitals and five rural clinics in the Deyang region of southwestern China. Interviews with mothers after delivery (urban n = 102, rural n = 99) were conducted before discharge and five focus group discussions were held. RESULTS: The prevalence of Caesarean section was high in both urban and rural areas (63.9 % urban vs. 68.4 % rural). After birth, nearly all mothers (98.0 % urban vs. 99.0 % rural) initiated breastfeeding. One week after delivery, the prevalence of exclusive breastfeeding was 8.0 % (9.8 % urban vs. 6.1 % rural), almost exclusive breastfeeding 34.5 % (29.4 % urban vs. 39.8 % rural), mixed feeding 56.0 % (58.8 % urban vs. 53.1 % rural), and exclusive formula feeding 1.5 % (2.0 % urban vs. 1.0 % rural). Breastfeeding initiation (<= two days after birth) was positively associated (Odds Ratio [OR] 1.97, 95 % Confidence Interval [CI] 1.11, 3.50) with exclusive and almost exclusive breastfeeding, whereas birth length under 50 cm (OR 0.48, 95 % CI 0.26, 0.87), mother's education > 12 years (OR 0.46, 95 % CI 0.24, 0.88) and mother's lack of knowledge about the importance of colostrum (OR 0.35, 95 % CI 0.14, 0.86) were negatively associated with almost exclusive breastfeeding. CONCLUSION: Although disparities between urban and rural areas exist, the situation of infant feeding is inadequate in both settings. The high prevalence of Caesarean section, the mothers' poor knowledge of the physiology of breast milk production, the mothers' lack of breastfeeding confidence, the widespread advertising of breast milk substitutes, and the changing perception of the function of breasts, may influence the unfavorable breastfeeding behavior observed in the study area. PMID- 27182281 TI - Living arrangements of the elderly in China: evidence from the CHARLS national baseline. AB - Declining fertility in China has raised concerns about elderly support, especially when public support is inadequate. Using rich information from the nationally representative China Health and Retirement Longitudinal Study (CHARLS) baseline survey, we describe the patterns of current living arrangements of the Chinese elderly and investigate their determinants and correlation with intergenerational transfers. We find that roughly 41% of Chinese aged 60 and over live with an adult child; living with a male adult child being strongly preferred. However another 34% have an adult child living in the same immediate neighborhood and 14% in the same county; only 5% have an adult child with none of them living in the same county. At the same time, a large fraction of the elderly, 45% in our sample, live alone or with only a spouse. In general, women, those from western provinces, and those from rural areas are more likely to live with or close to their adult children than their corresponding counterparts, but different types of intergenerational transfers play a supplementary role in the unequal distribution of living arrangements. Among non-co-resident children, those living close by visit their parents more frequently and have more communications by other means. In contrast, children who live farther away are more likely to send financial and in-kind transfers and send larger amounts. PMID- 27182283 TI - Machine learning algorithms for mode-of-action classification in toxicity assessment. AB - BACKGROUND: Real Time Cell Analysis (RTCA) technology is used to monitor cellular changes continuously over the entire exposure period. Combining with different testing concentrations, the profiles have potential in probing the mode of action (MOA) of the testing substances. RESULTS: In this paper, we present machine learning approaches for MOA assessment. Computational tools based on artificial neural network (ANN) and support vector machine (SVM) are developed to analyze the time-concentration response curves (TCRCs) of human cell lines responding to tested chemicals. The techniques are capable of learning data from given TCRCs with known MOA information and then making MOA classification for the unknown toxicity. A novel data processing step based on wavelet transform is introduced to extract important features from the original TCRC data. From the dose response curves, time interval leading to higher classification success rate can be selected as input to enhance the performance of the machine learning algorithm. This is particularly helpful when handling cases with limited and imbalanced data. The validation of the proposed method is demonstrated by the supervised learning algorithm applied to the exposure data of HepG2 cell line to 63 chemicals with 11 concentrations in each test case. Classification success rate in the range of 85 to 95 % are obtained using SVM for MOA classification with two clusters to cases up to four clusters. CONCLUSIONS: Wavelet transform is capable of capturing important features of TCRCs for MOA classification. The proposed SVM scheme incorporated with wavelet transform has a great potential for large scale MOA classification and high-through output chemical screening. PMID- 27182282 TI - Maximizing the Implementation Quality of Evidence-Based Preventive Interventions in Schools: A Conceptual Framework. AB - Increased availability of research-supported, school-based prevention programs, coupled with the growing national policy emphasis on use of evidence-based practices, has contributed to a shift in research priorities from efficacy to implementation and dissemination. A critical issue in moving research to practice is ensuring high-quality implementation of both the intervention model and the support system for sustaining it. The paper describes a three-level framework for considering the implementation quality of school-based interventions. Future directions for research on implementation are discussed. PMID- 27182284 TI - Achieving Depression Literacy: The Adolescent Depression Knowledge Questionnaire (ADKQ). AB - Mental health literacy appears to be an important target for prevention and intervention efforts. However, limitations exist in this literature base, including the lack of a validated measure to assess this construct. The Adolescent Depression Knowledge Questionnaire (ADKQ) was created to assess knowledge of depression and attitudes about seeking help (i.e., depression literacy) for mental health issues before and after introduction of a universal, school-based intervention, the Adolescent Depression Awareness Program (ADAP). The ADKQ measured depression knowledge and attitudes in 8,216 high school students immediately before ADAP was implemented and 6 weeks after. The latent structure of the Knowledge section was examined with attention to measurement invariance between males and females and type of instructor, as well as pre- to post-test. Categories were developed for the open-ended questions of the Attitudes section. A one-factor (General Knowledge) latent structure was the best fit to the data. The latent structure of the ADKQ did not differ by student's gender or type of instructor, nor did it differ based on pre- or post-test. Categories for the Attitudes portion of the ADKQ were developed. Psychometric evidence supports the ADKQ as a measure to evaluate adolescent depression literacy pre- to post-test and within several groups of interest (e.g., gender, facilitator). Categories for the Attitudes section of the ADKQ will allow for easier evaluation of this measure with quantitative data. PMID- 27182285 TI - DNA methylation mediates the effect of exposure to prenatal maternal stress on cytokine production in children at age 131/2 years: Project Ice Storm. AB - BACKGROUND: Prenatal maternal stress (PNMS) is an important programming factor of postnatal immunity. We tested here the hypothesis that DNA methylation of genes in the NF-kappaB signaling pathway in T cells mediates the effect of objective PNMS on Th1 and Th2 cytokine production in blood from 131/2 year olds who were exposed in utero to the 1998 Quebec ice storm. RESULTS: Bootstrapping analyses were performed with 47 CpGs across a selection of 20 genes for Th1-type cytokines (IFN-gamma and IL-2) and Th2-type cytokines (IL-4 and IL-13). Six CpGs in six different NF-kappaB signaling genes (PIK3CD, PIK3R2, NFKBIA, TRAF5, TNFRSF1B, and LTBR) remained as significant negative mediators of objective PNMS on IFN-gamma secretion after correcting for multiple comparisons. However, no mediation effects on IL-2, IL-4 and IL-13 survived Bonferroni correction. CONCLUSIONS: The present study provides preliminary evidence supporting the mediating role of DNA methylation in the association between objective aspects of PNMS and child immune states, favoring a Th2 shift. PMID- 27182286 TI - Rapid Identification of Major Histocompatibility Complex Class I Haplotypes Using Deep Sequencing in an Endangered Old World Monkey. AB - Immunogenetic data from wild primate populations have been difficult to obtain, due to logistic and methodological constraints. We applied a well-characterized deep sequencing method for MHC I typing, developed for macaques, to a population of wild red colobus to assess the feasibility of identifying MHC I-A/B haplotypes. Ten individuals produced sufficient data from blood and tissue samples to assign haplotypes. Eighty-two sequences were classified as red colobus MHC I alleles distributed across six MHC I loci. Individuals averaged ~13k reads across six MHC I loci, with 83% of all alleles representing either MHC I-A or MHC I-B loci. This study not only represents an important advance in the identification and genotyping of MHC in the endangered red colobus but also shows the potential for using this approach in other endangered wild primates. PMID- 27182287 TI - Drug-micronutrient interactions: food for thought and thought for action. AB - Micronutrients are indispensable for a variety of vital functions. Micronutrient deficiencies are a global problem concerning two billion people. In most cases, deficiencies are treatable with supplementation of the elements in lack. Drug nutrient interactions can also lead to micronutrient reduce or depletion by various pathways. Supplementation of the elements and long-term fortification programs for populations at risk can prevent and restore the related deficiencies. Within the context of Predictive, Preventive, and Personalized Medicine, a multi-professional network should be developed in order to identify, manage, and prevent drug-micronutrient interactions that can potentially result to micronutrient deficiencies. PMID- 27182288 TI - The bladder is not sterile: History and current discoveries on the urinary microbiome. AB - In the human body, there are 10 bacterial cells for every one human cell. This fact highlights the importance of the National institutes of Health's initiative to map the human microbiome. The Human Microbiome Project was the first large scale mapping of the human microbiome of 5 body sites: GI tract, mouth, vagina, skin and nasal cavity using culture-independent methods. The bladder was not originally tested because it was considered to be sterile and there were complexities regarding sample collection. Over the last couple years our team along with other investigators have shown that a urinary microbiome exists and for most individuals it plays a protective role. PMID- 27182289 TI - ESTIMATING HETEROGENEOUS GRAPHICAL MODELS FOR DISCRETE DATA WITH AN APPLICATION TO ROLL CALL VOTING. AB - We consider the problem of jointly estimating a collection of graphical models for discrete data, corresponding to several categories that share some common structure. An example for such a setting is voting records of legislators on different issues, such as defense, energy, and healthcare. We develop a Markov graphical model to characterize the heterogeneous dependence structures arising from such data. The model is fitted via a joint estimation method that preserves the underlying common graph structure, but also allows for differences between the networks. The method employs a group penalty that targets the common zero interaction effects across all the networks. We apply the method to describe the internal networks of the U.S. Senate on several important issues. Our analysis reveals individual structure for each issue, distinct from the underlying well known bipartisan structure common to all categories which we are able to extract separately. We also establish consistency of the proposed method both for parameter estimation and model selection, and evaluate its numerical performance on a number of simulated examples. PMID- 27182290 TI - Tunable Plasmonic Nanohole Arrays Actuated by a Thermoresponsive Hydrogel Cushion. AB - New plasmonic structure with actively tunable optical characteristics based on thermoresponsive hydrogel is reported. It consists of a thin, template-stripped Au film with arrays of nanoholes that is tethered to a transparent support by a cross-linked poly(N-isopropylacrylamide) (pNIPAAm)-based polymer network. Upon a contact of the porous Au surface with an aqueous environment, a rapid flow of water through the pores enables swelling and collapsing of the underlying pNIPAAm network. The swelling and collapsing could be triggered by small temperature changes around the lower critical solution temperature (LCST) of the hydrogel. The process is reversible, and it is associated with strong refractive index changes of Deltan ~ 0.1, which characteristically alters the spectrum of surface plasmon modes supported by the porous Au film. This approach can offer new attractive means for optical biosensors with flow-through architecture and actively tunable plasmonic transmission optical filters. PMID- 27182291 TI - On a State-Sponsored Sport System in China. AB - The gold medal success of China in recent Olympic Games can be traced to the advancement of the state-sponsored sport system (SSSS). While the program was developed initially through socialist ideals, it is more than a centralized government system to monopolize resources for glorified sport performance. Participation in competition is an inherent part of the human condition. Success in athletics is associated with national identity and has economic, social, and cultural implications. Because of this, it is essential that the SSSS adjust and improve to keep pace with other facets of China's quickly changing national reform. In association with emerging economic reform, some sports now receive equal or more funds from private investments compared to government allocation. The state-sponsored sport system must continue to adapt to maintain the Chinese tradition of excellence in competition. PMID- 27182292 TI - Dabbing the Skin Surface Dry During Ice Massage Augments Rate of Temperature Drop. AB - While ice massage (IM) is a rapid cooling technique used to facilitate therapeutic movements in the rehabilitation process, evidence of its efficacy over alternative therapeutic protocols is scarce. We determined whether dabbing the skin surface dry during a standard IM treatment would lead to greater rate of skin temperature reduction in comparison to without dabbing; and whether dabbing the skin would lead to an acute change in flexibility. Sixteen healthy volunteers received a "dabbing" and "non-dabbing" 7-minute IM treatment over the surface of each triceps surae muscle. Minute-by-minute temperature change in skin surface was evaluated using an infrared thermometer. Active (AROM) and passive (PROM) range of motion were evaluated via hand-held goniometer and passive stretch force was evaluated with an algometer. Dependent variables (reported as Mean +/- SD) were tested with two-way analysis of variance with repeated measures. Skin temperature ( degrees C) was reduced to with dabbing (5.8 +/- 1.1) in comparison to without dabbing (6.8 +/- 1.4), evoking significantly greater cooling at 1-min of ice massage (group X time interaction, p<0.01). However, after two minutes of IM, each method of application evoked similar surface temperatures. There was no significant difference in AROM, with dabbing (-0.63 +/- 2.55 degrees ) in comparison to without dabbing (1.18 +/- 2.90 degrees ), and no significant difference in passive-length tension relations (p>0.05) for either IM group. The dabbing protocol resulted in more rapid rate of temperature drop at 1-minute, however, both IM techniques are sufficient in cooling surface temperature after 2 minutes of IM. Further study is warranted to determine the clinical significance of the dabbing procedure. PMID- 27182293 TI - Do the Principles of Motor Program Editing Apply to Longer Sequences of Rapid Aiming Movements? Part I. AB - Prior work had shown that performing a shorter distance aiming movement prior to a longer distance aiming movement resulted in overshooting of the short movement and undershooting of the longer movement compared to repetition of the same movement. The main question was whether the same interference effects would be found in a three-movement sequence. Right-handed (N = 24) participants (aged 18 22) produced a sequence of two or three bimanual rapid lever reversals combining short (20 degrees ) and long (60 degrees ) movements with an intermovement interval of 2.5 s beginning with either the dominant or nondominant hand. Participants overshot the short target and undershot the long target when short and long movements alternated compared to same distance control conditions, but the effects were greater for the nondominant hand. Overall, the experiment demonstrated that parameter value switching was a major source of spatial inaccuracy in sequential aiming movements. PMID- 27182294 TI - Reviewing an Original Research Manuscript for the International Journal of Exercise Science: A Guide for Students and Professionals. AB - Considerations for the review process of manuscripts submitted to the International Journal of Exercise Science are presented. Initial steps to evaluation include reading the abstract to determine your ability as a reviewer, becoming familiar with the journal requirements, and formulating an initial impression of the manuscript. At this point an assessment is made to determine how the reviewer should treat the manuscript. If it is determined that the manuscript is acceptable with minor revisions, or may be acceptable with major changes, a full review should be performed. A full review of the manuscript requires a thorough examination of the major headings including the Introduction, Methods, Results, and Discussion. The written review is composed of two parts, a section with the decision that is composed of comments only for the editor, and a section that provides feedback to the authors. Specific comments to the authors should include an honest critique that aids in improving the manuscript. PMID- 27182295 TI - Do the Principles of Motor Program Editing Apply to Longer Sequences of Rapid Aiming Movements? Part II. AB - In Part I of this study, it was shown that performing a shorter distance aiming movement prior to a longer distance aiming movement resulted in overshooting of the short movement and undershooting of the longer movement compared to control conditions. However, the finding was limited, unexpectedly, to the nondominant hand. To replicate the prior result and to determine the effect of practice organization on movement accuracy, right-handed (n =24) participants (aged 18-22) produced a sequence of three rapid lever reversals combining short (20 degrees ) and long (60 degrees ) movements with an intermovement interval of 2.5 s with the dominant hand. Greater overshooting of the short movements and greater undershooting of the long movement was shown with random practice compared to blocked practice for both same distance and different distance sequences, although spatial errors were greater in the different conditions compared to the same conditions. Overall, the experiment demonstrated parameter value switching and practice organization as two major sources of spatial inaccuracy in sequential aiming movements. PMID- 27182296 TI - Changes in EMG and Finger Force with Repeated Hangs from the Hands in Rock Climbers. AB - The nature and degree of fatigue in muscles that control finger position during repeated sustained efforts in rock climbing have not been described. The purpose of this study was to identify changes in maximum hang time and forearm electromyogram (EMG) during repeated maximum duration hangs from a simulated rock feature. A second objective was to determine the effect of different recovery times between hangs upon changes in finger force. Five experienced rock climbers performed 2 test sessions on different days in a randomized order. Each session involved 8 repetitions of a maximum duration hang with either 1 min (R1) or 3 min (R3) resting recovery between hangs. Finger force (FF) was measured for the right hand via a piezoelectric force sensor fitted with a plate to accept the distal digits of four fingers. Peak EMG (EMGPK) and EMG Area (EMGAREA) were recorded from the anterior forearm for each hang and standardized as percent of maximum FF EMG prior to statistical analysis. Hang duration progressively decreased over repetitions but tended to plateau around repetition 5 for both R1 and R3 conditions. A significant difference was found for both recovery conditions and repetitions (p<.05) as well as a significant interaction of the two factors (p<.05) for hang duration. There were no significant differences for EMGPK among repetitions or between recovery conditions (p>.05). EMGAREA decreased initially with repeated hangs during both R1 and R3 but this trend tended to plateau at repetition 3 for the R3 condition. A significant difference was found in EMGAREA for both recovery conditions and trials (p<.05) as well as a significant interaction of the two factors (p<.05). Mean FF decreased between pre- and post hangs for both R1 and R3 however the difference was not significant. It was concluded that the overall decline in hang time is less with 3 min recovery vs 1 min recovery between hangs. Peak EMG does not appear to change despite this evidence of fatigue. A 3 min recovery interval between hang repetitions decreases the magnitude of fatigue experienced and enables a greater EMGAREA per hang. PMID- 27182297 TI - Exercise Induced Alterations in Rat Monocyte Number, Morphology, and Function. AB - The purpose of this study was to verify the histophysiological alterations in monocytes and macrophages induced by short periods of exercise. Male Wistar rats (age = 2 months, body weight = 200g) were divided into seven groups (N = 6 each): sedentary control (C), groups exercised (swimming) at low intensity for 5 (5L), 10 (10L), and 15 minutes (15L), and groups exercised at moderate intensity for 5 (5M), 10 (10M) or 15 minutes (15M). At moderate intensity the animals carried a load of 5% of body weight on their backs. Blood monocytes were evaluated for quantity and morphology, and peritoneal macrophages were analyzed for quantity and phagocytic activity. Data were analyzed using ANOVA and Tukey's post hoc test (p <= 0.05). Low intensity groups and 5M exhibited an increase in monocyte levels when compared with the control. There was an increase in monocyte cellular area for the 5L, 10L, 5M and 10M groups; monocyte nuclear area increased for the 10L, 5M and 10M groups in comparison with the control. There was an increase in peritoneal macrophages for the 15L, 10M, 15M and decrease for the 5M group. Macrophage phagocytic capacity increased for low intensity groups and for 10M group. The exercise performed for short periods modulated macrophage levels and function, and monocyte levels and morphology, in an intensity-dependent manner. The sum of acute responses observed in this study may exert a protective effect against sickness and may be used to improve health and lifespan. PMID- 27182298 TI - ? PMID- 27182299 TI - Undergraduate Research: Importance, Benefits, and Challenges. AB - Developing and maintaining undergraduate research programs benefits students, faculty mentors, and the university. Incorporating a research component along with a sound academic foundation enables students to develop independent critical thinking skills along with oral and written communication skills. The research process impacts valuable learning objectives that have lasting influence as undergraduates prepare for professional service. Faculty members at teaching intensive institutions can enhance learning experiences for students while benefiting from a productive research agenda. The university in turn benefits from presentations and publications that serve to increase visibility in the scientific community. Whether projects are derived through student-generated or mentor-generated means, students benefit from completion of exposure to the hypothesis-driven scientific method. PMID- 27182300 TI - Swim Positioning and its Influence on Triathlon Outcome. AB - Questions have been raised regarding which of the three legs of a triathlon influences the final finishing position. Some coaches subjectively believe that the swim and run are more important than the cycle, especially since the introduction of drafting during the cycle. This study analysed race position shifts between each of the three disciplines to assess the importance of the swim finish position and final finish position during draft legal Olympic distance triathlon events. Ten male and 10 female triathlon world cup events during one season were analysed. The results suggested that the triathlon swim leg is important because the winner exited the water in the first pack in 90% of elite male and 70% of elite female races. Correlations were also derived from finishing order for the whole triathlon and a finishing order that included the swim only, cycle only or run only time. For men, the average correlations for final finishing order with each of the swim, cycle and run, respectively, were 0.49, 0.67 and 0.86 and for the women; average correlations were 0.39, 0.67 and 0.85. Hence, this indicated that it was important to exit the water in the first pack and run well after cycling to achieve a successful final finishing position. PMID- 27182301 TI - Test-Retest Reliability of the Digijump Machine. AB - Repetitive jumping has been identified as a possible exercise modality able to provide sufficient stimulus to improve bone health. However, it is necessary to establish whether repetitive jumping can elicit a consistent physiological response with the ablity to monitor work rate. The purpose of this investigation was to determine the stability reliability of the Digijump device for the commonly used laboratory measures of oxygen uptake (VO2), heart rate (HR), and rate of perceived exertion (RPE). College-aged individuals (N = 17) completed two 3-min repetitive jumping bouts on the Digijump machine (120 jumps per minute, jump height = 1.27 cm) at least seven days apart. Stability reliability was calculated using the intraclass correlation coefficient derived from 1-way ANOVA. Absolute VO2 displayed the highest test-retest reliability (0.95), while the coefficient for relative VO2 was also acceptable (0.71). The test-retest reliability coefficients for HR (0.89), and RPE (0.75) were determined to be within acceptable limits. Coefficients for all variables compared well with the stability reliability reported for other ergometers such as the Stairmaster, treadmill, and cycle. This data represent an important step in determining the validity of the Digijump machine for physiological testing. PMID- 27182303 TI - Student Reflections on a Study Abroad Course to the 2008 Summer Olympics in Beijing. AB - The authors lead a study abroad trip to Beijing, China during the 2008 Summer Olympic Games. Included are reflections from the students who participated. Throughout the visit, students had the opportunity to complete learning outside of the traditional classroom setting. In addition, various challenges were faced and overcome which also constituted a learning experience and was the cause of reflection. The country of China and all of its historical landmarks had a great impression on these students, especially the day that was spent at the Great Wall. Finally, being able to be at the Olympic Games was a life-changing experience, from the Opening Ceremony to the events that were attended. In all, it was a thoroughly worthwhile adventure and one that we hope to replicate every two years. PMID- 27182302 TI - Resulting Shifts in Percentile and Standard Placements after Comparison of the BOD POD and DXA. AB - The purpose of this study was to determine the validity of the BOD POD(r) when compared to the DXA and if placement on a percentile chart and standard table is affected by any differences between the two measures. A total of 244 (27.7 +/- 10.8 yrs, 77.3 +/- 16.1 kg, 171.4 +/- 10.1 cm, 26.31 +/- 5.42 BMI) males and females between the ages of 18 and 52 were recruited to participate in this study. The participant's body fat percentage (%BF) was tested in random order on the BOD POD(r) and DXA during a 30-minute session following manufacturer's guidelines and procedures. Dependent t-test indicated the %BF measured by the BOD POD(r) (23.4% +/- 12.8) was significantly lower when compared to the DXA (29.5% +/- 12.1), p = .001. The Pearson's Product moment correlation was 0.95 (p = .001), indicating a very strong relationship between the two instruments. Using estimates of %BF from the BOD POD(r) also resulted in more favorable shifts on a percentile chart and standard table. Since a high correlation was evident between the two, the BOD POD(r) can be used as an instrument to track %BF changes over time during a diet and/or exercise intervention. However, caution should be made when classifying %BF with percentile charts or standard tables using the BOD POD(r) %BF estimates. PMID- 27182304 TI - Age-Related Differences in Systolic Blood Pressure Recovery after a Maximal Effort Exercise Test in Non-Athletic Adults. AB - The present study investigated the rate of systolic blood pressure recovery (SBPR) amongst three male age groups. Ninety-six apparently healthy, non-athletic adult males (48 young [23.91+/-4.58 years], 32 middle-aged [41.78+/-5.98 years] and 16 elderly [62.87+/-2.57 years]) participated in the study. Subjects performed a maximal-effort ergometer exercise test. Maximal oxygen uptake (VO2max) was measured during the exercise protocol; heart rate (HR) and SBP were measured before exercise (after 10 and 15 minutes of rest), during exercise (at 2 minute intervals), and at the first minute of post-exercise recovery and subsequently at 2-minute intervals until the recovery of SBP. Results showed that third-minute SBP ratio relative to 1 minute of recovery (SBPRy) was significantly lower (p<0.01; p<0.001) in the young (0.87+/- 0.06) when compared to middle aged (0.91 +/- 0.05) and elderly adults (0.93 +/- 0.04). Using bivariate correlation analysis, VO2max and %HR decline at 1 minute and 3 minutes of recovery, correlated with SBPRy in all age groups but after controlling for their confounders, only %HR decline in 3 min remained significantly correlated with SBPR in all the age groups. This study therefore showed age differences in SBPR after exercise with younger adults indicating faster recovery than older adults. After controlling for factors influencing SBPR, %HR decline in 3 min of recovery appeared to be a stronger contributor to age differences in SBPR than %HR decline in 1 min and VO2max. The reported data indicate the need to take age into account when interpreting SBPR after exercise during physical assessment of healthy individuals. PMID- 27182305 TI - Aerobic Capacity and Postprandial Flow Mediated Dilation. AB - The consumption of a high-fat meal induces transient vascular dysfunction. Aerobic exercise enhances vascular function in healthy individuals. Our purpose was to determine if different levels of aerobic capacity impact vascular function, as measured by flow mediated dilation, following a high-fat meal. Flow mediated dilation of the brachial artery was determined before, two- and four hours postprandial a high-fat meal in young males classified as highly trained (n = 10; VO2max = 74.6 +/- 5.2 ml.kg.min-1) or moderately active (n = 10; VO2max = 47.3 +/- 7.1 ml.kg.min-1). Flow mediated dilation was reduced at two- (p < 0.001) and four-hours (p < 0.001) compared to baseline for both groups but was not different between groups at any time point (p = 0.108). Triglycerides and insulin increased at two- (p < 0.001) and four-hours (p < 0.05) in both groups. LDL-C was reduced at four-hours (p = 0.05) in highly trained subjects, and two- and four hours (p <= 0.01) in moderately active subjects. HDL-C decreased at two- (p = 0.024) and four-hours (p = 0.014) in both groups. Glucose increased at two-hours postprandial for both groups (p = 0.003). Our results indicate that a high-fat meal results in reduced endothelium-dependent vasodilation in highly trained and moderately active individuals with no difference between groups. Thus, high aerobic capacity does not protect against transient reductions in vascular function after the ingestion of a single high-fat meal compared to individuals who are moderately active. PMID- 27182306 TI - Impact of Seated and Standing Bicycle Riding Position on Subsequent Running Performance. AB - This study examined the effects of cycling posture on subsequent running performance similar to the transition phase of a triathlon. Experienced, non elite triathletes completed two trials of a cycle-run transition. During the last three minutes of a 30 minute cycling bout, at power output equal to lactate threshold, subjects either remained seated (SEAT), or alternated seated and standing cycling (30 s at a time; ALT). Heart rate, RPE, minimum and maximum knee angle, stride frequency and length, and onset and duration of quadriceps and hamstrings activity were obtained at the end of a three-minute control run and at minutes 0, 2, & 4, of running after cycling transition. Repeated Measures ANOVA (condition X minute; p = 0.05) found control was significantly different than minute 0 for stride frequency and length, but not for minimum or maximum knee angle. EMG duration at minute 4 was less than all other time points for both quadriceps and hamstrings. Onset of muscle activity was not different for hamstring or quadriceps. Heart rate and RPE both increased over 15 minutes after transition and were higher for SEAT than ALT, however, there was no interaction (minute by position) for either variable. Results indicated changes in stride rate and length following cycling occur, but disappear within two minutes after the transition to running and do not differ between postures. Changes in duration of muscle activity may be related to changes in stride. Also HR and RPE differ between the SEAT and ALT cycling positions and over time. PMID- 27182307 TI - From the Editors: Assessing the International Journal of Exercise Science after One Year. AB - Western Kentucky University (WKU) strives to be a "leading American university with international reach." In an effort to contribute to that mission, Drs. Scott Lyons and James Navalta of the Exercise Science program endeavored in 2007 to start a student-focused, on-line journal. Working closely with Berkeley Press, the platform for the International Journal of Exercise Science (IJES) was established during the summer of 2007 and it went "live" in January 2008. The journal has now been on-line for over one year and has enjoyed great success, with quality research submitted from graduate and undergraduate students, as well as professionals. We at IJES look forward to continued success in 2009. PMID- 27182308 TI - Timing Carbohydrate Beverage Intake During Prolonged Moderate Intensity Exercise Does Not Affect Cycling Performance. AB - Carbohydrate beverages consumed during long-term exercise have been shown to attenuate fatigue and improve performance; however, the optimal timing of ingestion is unclear. Therefore, the purpose of this study was to determine if timing the carbohydrate ingestion (continual loading (CL), front-loading (FL), and end-loading (EL)) during prolonged exercise influenced exercise performance in competitive cyclists. Ten well-trained cyclists completed three separate exercise bouts on a bicycle ergometer, each lasting 2 hours at an intensity of ~67% VO2 max, followed by a 15-minute "all out" time trial. In the CL trial, a carbohydrate beverage was ingested throughout the trial. In the FL trial, participants ingested a carbohydrate beverage during the first hour and a placebo beverage during the second hour. In the EL trial, a carbohydrate beverage was ingested during the second hour and a placebo during the first hour. The amount of carbohydrate consumed (75 g) was the same among conditions. The order of conditions was single-blinded, counterbalanced, and determined randomly. Performance was measured by the work output during the 15-minute performance ride. There were no differences in work output among the three conditions during the final time trial. In the first hour of exercise, peak venous blood glucose was highest in the FL condition. In the second hour, peak venous blood glucose was highest in the EL condition. Following the time trial, venous blood glucose levels were similar among CL, FL, and EL. Overall, the timing of carbohydrate beverage consumption during prolonged moderate intensity cycling did not alter cycling performance. PMID- 27182309 TI - Influence of Body Composition, Oral Contraceptive Use, and Physical Activity on Bone Mineral Density in Premenopausal Women. AB - In premenopausal women, low bone density may reflect attainment of a lower peak bone mass which can increase risk of osteoporosis after menopause. The purpose of this study was to examine the relationship between total body, lumbar spine, and proximal femur bone mineral density (BMD) and body composition and oral contraceptive (OC) use in 18-30 year old women. Sixty-five healthy women, split into groups of oral contraceptive users (OC, n = 36) and non oral contraceptive users (Non-OC, n = 29), completed Baecke physical activity, calcium intake, and menstrual history questionnaires. Total body, AP lumbar spine, and dual proximal femur scans were performed using Dual Energy X-Ray Absorptiometry (DXA). Body composition measures were obtained from the total body scan analysis. No significant differences were found for BMD in OC users and non-users. Bone free lean body mass (BFLBM) and weight were positively correlated to all BMD sites, and fat mass was related to total body and L1-L4 spine BMD (p < 0.05). Stepwise regression analyses determined that weight was a significant predictor for all BMD sites (p < 0.05). When separating the two components of body weight, BFLBM was a significant predictor for all BMD sites, and fat mass only predicted total body BMD. In conclusion, this study indicates that weight and BFLBM are significant contributors to BMD in young healthy premenopausal women, and OC use did not influence the relationship between BMD and BFLBM. PMID- 27182310 TI - Exercise Bouts at Three Different Intensities Fail to Potentiate Concentric Power. AB - Postactivation potentiation (PAP) has been hypothesized previously to occur during voluntary, concentric actions. We tested the hypothesis that one of at least three different intensities of conditioning exercises would evoke potentiation of power during the concentric, bench press throw (BPT). Twelve men (age = 22.9 +/- 2.7 years, bench press 1 repetition maximum (1RM) = 1.20 +/- 0.12 kg.kg-1 body weight) completed five isotonic conditioning presses at ~55, 70, and 86% 1RM, in counterbalanced order, and on separate days. Average and peak power of the BPT using a load of 55% 1RM along with surface electromyography (EMG) of the triceps brachii were collected prior to and 4-minutes following each conditioning bout. Both average and peak power and EMG values (mean +/- SD), respectively, were evaluated using two-way analyses of variance with repeated measures. Significant main effect decreases (p < 0.05) in average (-18.6 +/- 4.9 W) and peak power (-37.4 +/- 9.9 W) occurred across the three different intensities evaluated. No main effects or interactions were observed with the EMG data. Contrary to the previously reported hypothesis, we were unable to demonstrate that conditioning exercise, with three different intensities, can evoke potentiation of power using a load equating to that which is optimum for power production. PMID- 27182311 TI - Modeling Oxygen Uptake during V1 Treadmill Roller Skiing. AB - The use of regression equations to predict oxygen uptake in relation to speed, grade, power output, and anthropometric characteristics is common in cardiac rehabilitation and athlete fitness testing. Research has suggested that sport specific testing improves the reliability of the test methodology and is appropriate for the development of effective training programs. This study focused on the development of a cross-country skiing specific predictor of maximal oxygen uptake based on treadmill speed, treadmill grade, gender, and body mass. This project simulated snow skiing on a large research treadmill using roller skis. A small sample size (N = 34) warranted the use of bootstrapping techniques and multiple regression analysis to develop a cross-country skiing specific model of oxygen uptake. The stability of each bootstrapped sample was confirmed via a cross-validation procedure. The equation of best resolve was: VO2 = -4.534 + 0.223(G) + 0.061(BM) + 0.139(TG) + 0.016(TS) in which G = Gender, BM = Body Mass, TG = Treadmill Grade, TS = Treadmill Speed. The resultant model can be used to design training programs, develop athlete fitness testing or research protocols, and to predict maximal oxygen uptake when sophisticated metabolic measurement equipment is unavailable. PMID- 27182313 TI - Exercise Science Academic Programs and Research in Brazil. AB - The International Journal of Exercise Science has enjoyed an association with several students and professionals from Brazil. In this invited editorial, professors from leading institutions in Brazil, Roberto Simao from Rio de Janeiro Federal University, and Jonato Prestes from the Federal University of Sao Carlos, share information regarding their programs relating to Exercise Science. They have provided information on academic components such as entrance requirements, progression through programs, and professional opportunities available to students following completion; as well as details regarding funding available to students to participate in research, collaboration, and specific research interests. PMID- 27182312 TI - The Influence of an Environmental Cue and Exercise on Food Consumption in College Students. AB - The purpose of this study was to determine the effect of an environmental cue (bowl size) on food consumption and to examine the influence of exercise on that relationship. This cross-sectional study included 286 college students attending a large Midwestern University. Upon arrival at an ice cream social for university students, participants were randomly given a small (8 oz) or large (12 oz) bowl and a 4-page survey addressing exercise and eating habits. At the social, participants were invited to dish themselves as much ice cream as they wanted and the amount consumed was determined by weighing the bowl with ice cream before and after consumption using a scale that measured to the nearest tenth of a gram. Participants who were provided the 12 oz bowl scooped and consumed significantly more ice cream than the participants provided the 8 oz bowl. Regular exercisers consumed more ice cream than non-regular exercisers regardless of statistical control for bowl size and body weight. Those participants who reported exercising previously that day also consumed significantly more ice cream than those not previously exercising; however, the difference was no longer significant after controlling for bowl size and body weight. Environment cues significantly influence food consumption and exercise may also influence subsequent food consumption but further research is needed. PMID- 27182314 TI - Academic and Research Programs in Exercise Science, South Korea. AB - We appreciate the opportunity to review academic curriculum and current research focus of Exercise Science programs in South Korea. The information of this paper was collected by several different methods, including e-mail and phone interviews, and a discussion with Korean professors who attended the 2009 ACSM annual conference. It was agreed that exercise science programming in South Korea has improved over the last 60 years since being implemented. One of distinguishable achievement is that exercise science programs after the 1980's has been expanded to several different directions. It does not only produce physical education teachers but also attributes more to research, sports medicine, sports, leisure and recreation. Therefore, it has produced various jobs in exercise-related fields. Some of exercise science departments do not require teacher preparation course work in their curriculum which allows students to focus more on their specialty. Secondly, we believe we South Korea has caught up with advanced countries in terms of research quality. Many Korean researchers have recently published and presented their investigations in international journals and conferences. The quality and quantity of these studies introduced to international societies indicate that Exercise Science programs in South Korea is continuing to develop and plays an important part in the world. PMID- 27182315 TI - Physical Activity is Associated with Percent Body Fat and Body Composition but not Body Mass Index in White and Black College Students. AB - The objective of this study was to examine the association of self-reported physical activity (PA) with body composition in 290 college students (49% male, 60% White) 18-25 years of age. Outcome measures included: self-reported PA levels calculated in MET-hrs.wk-1 from the International Physical Activity Questionnaire (IPAQ); body mass index (BMI; in kg.m-2); and body composition variables estimated by dual-energy X-ray absorptiometry (DXA). Mean activity levels of the sample were 39.8 +/- 23.8 MET-hrs.wk-1. Participants were divided into quartiles of PA levels: >=0 to <24.0, >=24.0 to <34.0, >=34.0 to <51.25, and >=51.25 MET hrs .wk-1 and body composition variables were compared by group. Chi-square analyses revealed a significant difference for gender by PA quartile [chi2 (3, N=290) = 32.42, p < 0.0001], and for gender by race by PA quartile [chi2 (9, N=290) = 37.82, p < 0.0001]. MET-hrs.wk-1 was inversely correlated with %BF (r = 0.40, p < 0.0001) but not BMI (r = 0.05, p = 0.43). When comparing body composition variables across PA quartiles, no significant differences were observed for BMI; however, subjects in the highest quartile of PA had a lower percent body fat (%BF) and fat mass (FM), and a higher lean-tissue mass (LTM) compared to subjects in the other three groups. In this cohort of young adults, participants in the highest activity group had a more fit body composition profile (e.g., lower %BF, lower FM, and higher LTM) which was not reflected in BMI and was independent of gender and race. PMID- 27182316 TI - The Effects of Tempur Insoles on Ground Reaction Forces and Loading Rates in Running. AB - Runners often experience over-use injuries. Ground reaction force (GRFs) patterns have been associated with these over-use injuries; however, it is not solely the magnitude of GRFs, but also the rate at which they are applied that lead to lower extremity injury. Many recreational runners will use over-the-counter insoles as a method of treating or preventing injury. Therefore, the purpose of this study was to examine the efficacy of two insoles on peak GRFs and loading rates. It was hypothesized that no differences in peak GRFs or loading rates would exist with the addition of two insoles during running. Twelve subjects (7 females; 5 males) performed seven running trials in each of the following conditions: no insoles (NORM), over-the-counter insoles (OTC) and memory-foam insoles (TEMPUR). GRFs were recorded using a force plate (1440Hz; AMTI) while subjects ran across a 15 meter lab. A 2 x 3 (gender x insole) repeated measures ANOVA was used to compare the effects of insoles on loading rate and ground reaction forces. Alpha level was set at p <0.05. The current study found no statistical differences in loading rate or GRFs between the insole and no insole conditions. Furthermore, there was no gender effect in any condition. The findings of the current study suggest that insoles do not attenuate shock or decrease loading rate. The lack of shock attenuation associated with insoles suggests they do not protect the lower extremity from injury. PMID- 27182317 TI - Predictors of ADL Disability in Culturally Diverse Older Adults. AB - The purpose of this study was to utilize the disablement pathway model to examine the contribution of physical function, dyspnea, and pain to disability in activities-of-daily-living (ADL) in culturally diverse older adults. Participants were 51 older adults (age = 69.0 years +/- 9.7; 76.5% African-American, 51.0% < high school education, 52.9% < $20,000 annual income) from an urban community center and an independent living housing facility for seniors. Participants completed the Functional Status Index (FSI), which provides ratings of need for assistance (FSIA) and pain (FSIP) with ADL, the Continuous Scale Physical Functional Performance 10-item Test (CS-PFP10), and an analog dyspnea scale. Hierarchical multiple regression analyses revealed that facility, physical function, pain, and dyspnea accounted for 50.5% of the variance in disability and that pain (beta = .43, p < .01) and physical function (beta = -.39, p < .01) were the only significant predictors. In the second model, facility, dyspnea, and pain explained 27.6% of the variance in physical function, and facility (beta = .39, p < .01) and dyspnea (beta = -.26, p = .05) were the only significant predictors. Based on the disablement pathway model, physical functional improvement and pain prevention and management should be targeted when designing culturally appropriate strategies for delaying disability and maintaining independent life. PMID- 27182318 TI - Balance Across Boundaries: Service-Learning from an International Perspective. AB - Service-Learning provides students, faculty and community partners an opportunity to go beyond classroom and laboratory instruction to the application of theoretical principles, and the development of civic responsibility by forging meaningful relationships with community partners. Service-learning also enables faculty to broaden the cultural sensitivity and international exposure of students by engaging students in directed, purposeful projects aimed at supporting the goals of both the college and the international partners. We have a unique opportunity in Exercise Science to make lasting changes and improve global conditions relating to student learning and the physical inactivity crisis. The purpose of this article is to define service-learning, describe different types of service-learning projects, and discuss service-learning opportunities in international settings. PMID- 27182319 TI - Evaluation of Hand-to-Hand Bioelectrical Impedance Analysis for Estimating Percent Body Fat in Young Adults. AB - Purposes were to (a) to examine the validity and precision of a hand-to-hand bioelectrical impedance analyzer (HBIA) and (b) to determine the effect of an acute sub-maximal aerobic exercise bout on HBIA percent body fat (%BF) measures. Forty-one young adults (21 women; 20 men) visited the laboratory for body composition assessment on two separate occasions. During the control session, %BF was assessed by HBIA twice, before and immediately after 30 min of rest, and once by air-displacement plethysmography (ADP), using the BOD POD, which was considered the criterion method for comparison. During the exercise session, HBIA %BF measurements were determined prior-to and immediately after 30 minutes of moderate-intensity treadmill exercise. HBIA significantly underestimated %BF in the total sample (mean difference (MD) = 1.4 +/- 4.3%) and, when examined by gender, in the women (MD = 2.4 +/- 4.1%). The standard errors of estimate (range 4.1-4.3%) also exceeded the recommended range for accuracy (<3.5%). Following exercise, there was minimal, but statistically significant reduction in HBIA measured %BF pre- to post-exercise for the total sample (19.6 +/- 6.0 vs. 19.3 +/ 6.0%; p = 0.011). HBIA underestimated %BF when compared to ADP and the individual prediction error exceeded current recommendations when assessing young adults. In addition, performing sub-maximal aerobic exercise prior to the assessment decreased the %BF estimate. When one factors the exercise-induced alterations with the currently observed tendency for HBIA to underestimate %BF, it is apparent that exercise may further reduce the accuracy of this method. PMID- 27182320 TI - The Short-Term Effect of Whole Body Vibration Training on Sprint Start Performance in Collegiate Athletes. AB - Whole body vibration (WBV) is characterized by a vibratory stimulus emitted throughout the body through the use of a vibrating platform on which the subject stands. Studies have shown over 30% increases in maximal explosive strength such as maximal speed biceps curl as well as increases in maximum dynamic force such as maximal sitting bench pull as the result of vibration. The purpose of this study was to investigate the effects of short term whole-body vibration on sprint starts among collegiate track athletes. On the first day eleven subjects were randomly assigned to either a non-vibration or vibration group for initial testing. The vibration group used whole body vibration along with their normal warm-up routine while the non-vibration group did not. Force measurements were taken where the starting blocks were placed using a force plate embedded under the track surface following the warm up. One week later the groups alternated. The results were then compared between vibration and non-vibration groups for individual athletes. The vibration protocol occurred for 60 s at 26 Hz with an amplitude of 4mm on a Galileo 2000 platform. Repeated measures analysis of the variance showed peak resultant force was 6% greater when the vibration platform was utilized prior to the start (p=0.013). Further research is needed to determine whether any meaningful differences exist in sprint start velocity as a result of WBV. There were no observed differences in the 30m sprint times. PMID- 27182321 TI - Determination of Force Coresponding to Maximal Lactate Steady State in Tethered Swimming. AB - The main aim of the present investigation was to verify if the aerobic capacity (AC) measured in tethered swimming corresponds to the maximal lactate steady state (MLSS) and its correlation with 30 min and 400m free style swimming. Twenty five swimmers were submitted to an incremental tethered swimming test (ITS) with an initial load of 20N and increments of 10N each 3min. After each stage of 3min, the athletes had 30s of interval to blood sample collections that were used to measure blood lactate concentrations ([La-]). The ACBI was determined by the abrupt increase in [La-] versus force (F). The points obtained between [La-] versus force (N) were adjusted by an exponential curve model to determine AC corresponding to 3.5mmol.l-1 (AC3.5) and 4.0mmol.l-1 (AC4.0). After these procedures, the swimmers performed maximal efforts of 30min and 400m in free style swimming. We used the distance performed in 30min and the time performed in 400m to calculate the median velocities (i.e. V30 and V400) of these protocols. After one week, in order to measure the MLSS, nine athletes performed three 30 min tethered swimming efforts with intensities of 90, 100, and 110% of ACBI. The ANOVA one-way was used to compare the ACBI, AC3.5 and AC4.0. Correlations between ACs, and between ACs and V30 and V400 (p<0.05) were determined using the Pearson's correlation coefficient. The intensity corresponding to 100% of ACBI was similar to the MLSS. It was observed significant correlations of the aerobic capacities (i.e. ACBI, AC3.5 and AC4.0) with V30 (r>0.91) and V400 (r>0.63). According to our results, it is possible to conclude that the ACBI corresponds to the MLSS, and both the AC - individually determined - and the AC - determined using fixed blood lactate concentrations of 3.5 and 4.0mmol.l-1 - can be used to predict the mean velocity of 30min and 400m in free style swimming. In addition to that, the tethered swimming system can be used for aerobic development in places where official sized swimming pools are not available, such as rehabilitation clinics and health clubs. PMID- 27182323 TI - From the Editors: Assessing the International Journal of Exercise Science after Two Years. AB - The popularity of the International Journal of Exercise Science continues to rise. As a student-focused journal, we are pleased to provide these future professionals with opportunities to gain experience with the peer review process, both through submitting their original work and as manuscript reviewers. Our editorial process is changing as section editors with specialties within the field of exercise science have agreed to take on these responsibilities. In addition, we are proud to also publish conference proceedings from various meetings held around the world. A list of individuals who have reviewed manuscripts throughout the last year is included. PMID- 27182322 TI - Multiple Models Can Concurrently Explain Fatigue During Human Performance. AB - One of the most commonly and thoroughly studied paradigms of human performance is fatigue. However, despite volumes of research there remains considerable controversy among scientists regarding definitive conclusions about the specific mechanism(s) contributing to fatigue. Within the literature there are three primary yet distinctly different governing ideas of fatigue; the traditionally referenced central model and peripheral model as well as the emerging central governor model (CGM). The CGM has recently been advocated by a limited number of researchers and is suggestive of a more integrative model of fatigue when compared the traditional peripheral and central models. However, more work is needed to determine the specific and perhaps synergistic roles of each paradigm during exercise or sport activity. This article contains three components; (1) a brief overview of the problems associated with defining fatigue, (2) a description of the models governing interpretation of fatigue and, (3) a presentation of multiple interpretations of selected data to demonstrate that some results can be reasonably explained using multiple models of fatigue, often concurrently. The purposes of this paper are to reveal that a) perhaps it is not the results that suggest a certain paradigm of regulation, yet that it may be a product of an a priori definition that is being employed and b) an integrative model of central and peripheral fatigue may present a plausible explanation for fatigue vs. adherence to the notion that each paradigm is mutually exclusive. PMID- 27182324 TI - Independent Multiple Correlates of Post-Exercise Systolic Blood Pressure Recovery in Healthy Adults. AB - The aim of the present study was to evaluate the independent relationships of systolic blood pressure recovery (SBPR) with age, sex, body mass index (BMI), waist circumference (WC), resting heart rate (HR), physical activity, and cigarette smoking in healthy adults. Subjects performed cycle ergometer exercise at progressive incremental workloads until subjects reached 80% of their age predicted maximum HR. Blood pressure (BP) was measured before exercise (after 10 and 15 minutes of rest), during exercise (at 2-minute intervals), immediately after exercise (within the first minute) and subsequently at 2-minute intervals until recovery to baseline. The ratio of third-minute SBP relative to first minute post-exercise SBP was used as the SBPR variable. Our results indicated independent correlations (p<0.05) between SBPR and age, resting HR, physical activity and cigarette smoking (r =0.473; 0.192; -0.262; 0.102 respectively in males and r =0.113; 0.315; -0.637; 0.104 respectively in females). BMI associated positively (r =0.106; p<0.01) with SBPR in males but not in females (r =0.092), while WC was predictive of SBPR in females (r =0.212; p<0.01) but not in males (r =0.005). Age in men and physical activity in females were the strongest predictors of SBPR. The present findings in which SBPR is associated with risk factors of cardiovascular abnormalities strengthen the previously reported significance of SBPR after exercise test as a prognostic tool for the evaluation of cardiovascular abnormalities. Additionally, it may help clinicians to define and interpret the mechanisms behind changes in postexercise SBP responses in adults in future investigations. PMID- 27182325 TI - Acute Exercise in Vietnam Veterans is Associated with Positive Subjective Experiences. AB - A person's subjective experience to their first exercise session is likely to influence their long-term adherence to regular exercise. The aim of the current pilot study therefore is to quantify the subjective exercise experience of previously sedentary Vietnam War Veterans undertaking an initial bout of one of three different exercise interventions. Thirty-two Vietnam Veterans presenting with one or more chronic diseases/conditions participated in one of three acute exercise bouts: 1) lower-body vibration, upper-body resistance and stretching (WBVT); 2) lower-body vibration, upper-body resistance, aerobic exercise and stretching (WBVT+CV); and 3) full-body resistance, aerobic exercise and stretching (R+CV). Pre and post acute exercise measures of positive well being, psychological distress and fatigue were assessed with the Subjective Exercise Experiences Scale (SEES). A 3(conditions) * 2(time) repeated measures ANOVA with post-hoc Tukey HSD was used to identify any significant differences in SEES between exercise groups and pre and post-exercise. All interventions increased positive well being, with WBVT and R+CV reporting improvements across all areas of the SEES. The WBVT+CV group reported slightly increased psychological distress and the greatest increase in fatigue. An acute bout of exercise increases positive well-being in previously sedentary War Veterans however a longer duration exercise bout containing multiple exercise modes may be too demanding for this population. Exercise professionals should consider commencing with a simple program to minimise psychological distress and fatigue as this may negatively impact on exercise adherence. PMID- 27182326 TI - A Comparison of Three Computer-based Methods Used to Determine EMG Signal Amplitude. AB - Electromyography is a commonly used method to determine relative effort and neuromuscular drive to skeletal muscle. A limitation of the interpretation of EMG within the literature is the many methods used to determine the intensity of muscle activation. In the current study, ten healthy young adults performed a level walking task while EMG was recorded from the tibialis anterior, medial gastrocnemius and fibularis longus. The EMG data were rectified and smoothed using the root mean squared (RMS). Peak RMS (pRMS), mean RMS (mRMS) and integrated EMG (iEMG) were normalized to the peak value within the subject and were used to determine EMG amplitude. A 3*3 repeated measures analysis of variance was used to determine significant differences between the methods of determining EMG amplitude. The findings of the current study show that pRMS produced significantly lower EMG amplitudes than mRMS or iEMG values. Furthermore, mRMS and iEMG produced nearly identical normalized EMG amplitudes. Based on the findings of this study and the components of each measurement of EMG amplitude, it is suggested to use mRMS to determine EMG amplitude. PMID- 27182327 TI - Heat Stress and Injury Prevention Practices During Summer High School Football Training in South Texas. AB - The purpose was to describe practice conditions influencing the risk of heat stress to athletes in summer football training in South Texas high schools, and to compare these conditions to ACSM recommendations for heat stress/injury risk reduction in this population. Thirty (N=30) high school summer football practices were observed. Wet bulb globe temperature (WBGT) was measured before/after practices and practices were observed for: duration/structure; athlete clothing; and rest break frequency/duration/content. Practices averaged 125+/-31 min and WBGT (pre- to post-practice) was 29.7+/-2.1 degrees C to 31.2+/-2.2 degrees C for morning, and 31.2+/-1.6 degrees C to 28.9+/-1.2 degrees C for evening practices. Most practices included contact (93%), and a majority were full-contact (53%). Most athletes wore full pads (83%) and medium/dark colored clothing (73%). Outside of scheduled breaks athletes removed helmets (63%), sat/knelt (63%), and had access to fluid (90%). Athletic trainers were present at 93% of the practices. A typical practice had 3 rest breaks, each lasting approximately 5 min. During breaks, athletes were provided fluid (93%), removed helmets (89%), and sat/knelt (76%), but were rarely provided shade (2%). While none of the practice sessions were conducted in conditions warranting the cancellation of outside activity (WBGT>33.1 degrees C), the environmental data confirms that this region presents athletes with a very high risk of heat stress/injury. While a majority of the schools were taking many of the precautionary measures recommended by ACSM, many of the guidelines were not being followed. Governing bodies of high school athletics need to encourage compliance with recommendations for the reduction of heat stress/injury in this population. PMID- 27182328 TI - Effect of the E3 Fitness Grips on Running Economy. AB - The purpose of this study was to evaluate the effect of the E3 Fitness Grips (BioGrip, Inc., Rancho Cordova, CA) on running economy, as measured by oxygen uptake (VO2), and heart rate (HR) during submaximal treadmill running. Eleven subjects, seven female and four male, completed a submaximal running test on a treadmill while VO2 and HR were measured continuously. After achieving steady state at a speed and grade that elicited a VO2 equivalent to 70% VO2max, the subjects ran for five minutes holding the E3 Fitness Grips (G) and five minutes without the grips (NG). The tests were counterbalanced so half of the subjects held the grips first and half completed the NG condition first. The difference in VO2 and HR between the G and NG conditions were compared to determine the effect on running economy. The mean VO2 (33.2+/-4.6 vs. 33.2+/-4.6 ml.kg-1.min-1, p=0.96) and mean HR (172.0+/-8.9 vs. 172.8+/-8.9 beats.min-1, p=0.38) were not significantly different between the G and NG conditions during submaximal running. These findings suggest that the E3 Fitness Grips do not significantly alter running economy, as measured by VO2, or HR during submaximal treadmill running. PMID- 27182329 TI - Asymmetry of Force Fluctuation During Low Intensity Isometric Contraction in Leg Muscle. AB - The purpose of this study was to investigate the asymmetry of force fluctuation in the leg muscles during isometric knee extension and flexion. Twenty healthy males (21+/-2 years) performed the maximal voluntary isometric contraction (MVC) in knee extensor and flexor. On the basis of MVC measurement, the subjects performed sustained isometric knee extension and flexion for 15s at levels corresponding to 10%, 20% and 30% MVC. The main findings of this study were: (1) a greater force fluctuation was found in the stronger MVC limb than in the weaker MVC limb at 30% MVC; (2) no difference was found in the force fluctuation between the stronger and weaker MVC limbs at 10% and 20% MVC; and (3) significant positive correlations were found between the target force values and the force fluctuation at each contraction intensity. These results suggest that: (1) asymmetry of force fluctuation increases with load, (2) asymmetry of the force fluctuation is observed at more than 30% MVC intensity; and (3) if the contraction intensity is same relatively loads (% MVC), force fluctuation is increase with absolute load (target force value). Force fluctuation influence the functional ability of an individual in controlling finger or limb movements in daily life. Further, asymmetry of force fluctuation might influence for more than 30% MVC of daily activities. PMID- 27182330 TI - Concurrent Visual Feedback, Practice Organization, and Spatial Aiming Accuracy in Rapid Movement Sequences. AB - While the availability of visual feedback is a well-known factor influencing the accuracy of rapid aiming movements, little is known about how vision might interact with a contextual variable like practice organization. In the current study, the interaction of concurrent visual feedback (CVF) and practice organization on aiming movement accuracy was investigated in the dominant limb of 40 college-aged participants. Participants performed "triplets" of rapid aiming movements with a lightweight lever in the sagittal plane involving short (20 degrees ), medium (40 degrees ), long (60 degrees ) distances and were randomly assigned to one of four groups (n=10) in a 2 (Group: Blocked Practice, Random Practice) * 2 (Vision: CVF, no CVF) factorial design. Participants performed 24 triplets in acquisition and 10 triplets of a novel pattern (15 degrees -45 degrees -15 degrees ) on transfer. Movement time was controlled by a metronome set at 1.43 cycles per second resulting in a cycle time of approximately 700 ms per movement. The constant error and overall error in distance were calculated for each distance and analyzed with separate 2 (Group) * 2 (Vision) * 3 (Movement) ANOVAs with repeated measures on the last factor. When CVF was available, contextual interference effects were shown by better accuracy for the blocked practice groups during acquisition compared to the random practice group. Without CVF, participants tended to overshoot the targets and contextual interference effects were minimized during acquisition and on the first transfer trial. Random practice resulted in better transfer performance compared to blocked practice for both vision conditions when all transfer trials were included in the analysis. The findings contributed to the current literature by demonstrating the importance of practice context and visual feedback to aiming accuracy. PMID- 27182331 TI - Prevalence of Plagiarism in Manuscript Submissions and Solutions. PMID- 27182332 TI - Recreational cyclists: The relationship between low back pain and training characteristics. AB - This study investigated the relationship between low back pain (LBP) and training characteristics in recreational cyclists. Purposive sampling was used to recruit sixty-six recreational cyclists from nine cycling clubs. Participants completed a survey reporting training characteristics and LBP behaviour during a usual week of cycling. This included percent of time spent cycling in three common riding positions, cycling terrain, average cycling pace, number of gears, days per week cycled and number of cycling events per year. Fifty percent reported LBP during or after cycling or smoking and LBP. Cyclists who reported LBP cycled significantly further in a usual week of cycling than cyclists who did not report LBP (p=0.022). An odds ratio indicated that people who cycle 160 km or more per week are 3.6 times as likely to experience LBP compared with people who cycle less than 160 km per week (OR=3.6, CI=1.29-10.15). Preference for riding with the hands on the brakes approached significance with respect to LBP reports (P=0.06). No other significant relationship between LBP and training characteristics was identified. In order to reduce the risk of LBP recreational cyclists who report LBP should consider decreasing cycling distance to less than 160 km per week. PMID- 27182333 TI - Objective and subjective assessments of normal walking pace, in comparison with that recommended for moderate intensity physical activity. AB - Despite its common application and widely reported health benefits, walking, in relation to pace and intensity, is under-researched. Few studies have addressed whether people normally walk at a pace that meets the public health recommendations for moderate intensity physical activity (1.34-1.79 ms-1) and there is no known research on individuals' perceptions of factors which influence walking pace. This study aimed to objectively assess if participants were reaching the pace required for moderate intensity physical activity during normal walking. This was examined via a Global Positioning System (GPS) over a 1 km outdoor walk and a timed 150 m trial. In both tests participants (n=10, 3 men, 7 women, mean age 54+/-8 y) were instructed to walk at their normal pace. Through short interviews, the study also investigated the factors that participants' thought influenced their pace. All participants successfully walked at a pace considered as moderate intensity (>=1.34 ms-1). Height was significantly correlated with normal walking pace. The interviews provided an in depth insight into factors that affect walking pace; ground surface and footwear were mentioned frequently and the influence of the weather provided conflicting views, prompting a need for further research in the area. The GPS device showed enormous potential as a human locomotion measurement tool, enabling participants to walk unobstructed and unobserved in an outdoor setting, making the results relevant to real life situations. PMID- 27182334 TI - Association of body surface area and body composition with heart structural characteristics of female swimmers. AB - In healthy nonathletic populations, some left ventricle (LV) parameters such as LV mass (LVM) and LV end diastolic dimension (LVEDD) can be predicted by some of body size parameters such as body surface area (BSA), fat-free mass (FFM), and height (H). These body size parameters use to remove covariate influence of body size from cardiac dimension variables and allow comparisons to be made between individuals and groups of different body size. Endurance exercise has been associated with changes in LV size and body composition of athletes. The aim of this study was to evaluate in 30 trained female swimmers (12-17 y) possible correlations between BSA, FFM, fat mass (FM) determined by bioelectrical impedance analyzer(BIA); and a range of cardiac dimensions derived by echocardiography. Univariate correlations were studied between left ventricular and body size variables. Stepwise multiple linear regression was performed to determine the best determinants of LV variables. LVM and LVEDD had a significant relation with FFM (P<0.001) and BSA (p<0.05). Left ventricle posterior wall thickness (PWT) had a significant relation with BSA (p<0.001) and FFM (p<0.005). No relation was found between heart's structural variable (LVM, LVEDD, LVESD and PWT) and FM. Using a multivariate regression analysis, FFM was the only independent predictor of both LVM (R2=0.541, P<0.001) and LVEDD (R2=0.189, P<0.05). These results suggest that Correction of LVM and LVEDD by FFM in athletes may be more appropriate than other measures of body size for indexing absolute amounts of LV dimension. Yet further researches in other athletes are required to confirm these findings. PMID- 27182335 TI - Monitoring Training Load in Indian Male Swimmers. AB - The present study was initiated to monitor the training load with the magnitude of impact on the hormone concentrations such as testosterone, cortisol and T/C (Testosterone/Cortisol) ratio during the three phases of training (i.e. preparatory, pre-competitive, and competitive phases) in Indian male swimmers preparing for the 2010 Commonwealth Games. Blood samples were collected at the end of each training phase and hormone concentration was determined by ELISA. Our results reveal that testosterone concentration and the T/C ratio significantly decreased and the cortisol concentration increased in the subsequent periodized cycle. Change in hormone concentration was associated with the intensity and duration of individual exercise sessions. The greatest performance enhancement was realized with the lowest plasma cortisol, highest testosterone, and a high T/C ratio. Monitoring of these hormones also have implications for identifying and preventing overreaching in swimmers. PMID- 27182336 TI - Perceived Muscle Soreness in Recreational Female Runners. AB - : The purpose of this study was to determine if rating of perceived exertion correlated with perceived muscle soreness during delayed onset muscle soreness (DOMS) in female runners. This study examined the pre and post running economy measures and perceived muscle soreness before and after a 30-min downhill run (DHR) at -15% grade and 70% of the subjects predetermined maximum oxygen uptake (VO2 peak). Six female recreational runners (mean age = 24.5) performed level running at 65%, 75%, and 85% of their VO2 peak prior to DHR (baseline economy runs), as well as, immediately following and 4 successive days after the DHR. RESULTS: Subjective response related to perceived muscle soreness increased significantly from a mean of 2 (pre DHR) to 62 (2 days post DHR) on a scale of 1 100. Creatine kinase levels and oxygen consumption increased post DHR compared to pre DHR. Rating of perceived exertion did not change between the economy runs performed prior to or at any point after the DHR. CONCLUSION: Perceived muscle soreness is a better tool than the RPE scale to monitor exercise intensity for recreational female runners during periods of DOMS and running economy is adversely affected by DOMS. PMID- 27182337 TI - Does Standing on a Cycle-ergometer, Towards the Conclusion of a Graded Exercise Test, Yield Cardiorespiratory Values Equivalent to Treadmill Testing? AB - Graded exercise testing (GXT), per a cycle-ergometer (CE), offers safety and monitoring advantages over treadmill (TM) GXT. Unfortunately, CE-VO2max and some other cardiorespiratory (CR) variables are frequently lower than TM-GXT values. It has been difficult to compare TM and CE-GXT values. However, it was hypothesized that standing towards the conclusion of the CE-GXT (Stand-CE) might increase CE values to those equal to TM-GXT. If Stand-CE and TM-GXT CR values were equal, Stand-CE-GXT could become the method of choice for GXT for the general population. The purpose of this investigation was to investigate the effect of Stand-CE on CR variables. An intentionally diverse sample (N = 34, 24 males and 10 females, aged 18-54 y, with VO2max values 25-76 ml/kg/min) representing the "apparently healthy" general population participated. Volunteers completed two GXT trials, one per TM (Bruce protocol) and the other per a MET-TM matched CE-GXT where initially seated participants stood and pedaled after their respiratory exchange ratio (RER) reached 1.0. Eighteen participants underwent a third MET-TM-matched trial where they remained seated throughout GXT (Sit-CE). Trials were counter-balanced with at least 48 h between GXT. There were significant statistical differences (p < 0.05) between TM and Stand-CE per matched-samples T-test (N = 34) on the following variables: VEmax (TM = 115 +/- 24.4 l/min, Stand-CE = 99.4 +/- 28.1), VCO2max (TM = 4.26 +/- 0.9 l/min, Stand-CE = 3.56 +/- 0.84), VO2max (TM = 44.9 +/- 9.1 ml/kg/min, Stand-CE = 39.3 +/- 9.0), METSmax (TM = 12.8 +/- 2.6 METS, Stand-CE = 11.2 +/- 2.5), and HRmax (TM = 175 +/ 13 bpm, Stand-CE = 166 +/- 12). One-way repeated measures ANOVA (N = 18) demonstrated no statistical differences among all trials: VEmax (TM = 112.8 +/- 25.3 l/min, Stand-CE = 102.3 +/- 25.2, Sit-CE = 107.3 +/- 33.1), VCO2max (TM = 4.17 +/- 0.99 l/min, Stand-CE = 3.62 +/- 0.80, Sit-CE = 3.55 +/- 0.83), VO2max (TM = 47.1 +/- 9.8 ml/kg/min, Stand-CE = 42.0 +/- 9.0, Sit-CE = 43.3 +/- 8.9), METSmax (TM = 13.5 +/- 2.8 METS, Stand-CE = 12.0 +/- 2.6, Sit-CE = 12.4 +/- 2.5), and HRmax (TM = 176 +/- 13 bpm, Stand-CE = 171 +/- 12, Sit-CE = 173 +/- 11). Results of this investigation suggest that TM-GXT CR values are larger than Stand CE, and Stand-CE values are not different from Sit-CE. Future studies will test validity of these findings per gender, aerobic training status, in populations that are highly skilled with TM and CE (tri-athletes), children, the elderly, and diseased populations. PMID- 27182338 TI - Does a Physical Education Bout Alter Percent Body Fat and the Adiposity Health Risk Classification When Using Leg-to-leg Bioelectrical Impedance Analysis in Girls? AB - The purposes of this investigation were to determine: 1) whether a structured in school physical education exercise bout altered the leg-to-leg bioelectrical impedance analysis (LBIA) determined percent body fat (%BF) value; and 2) whether the potential exercise-induced %BF magnitude of change altered the health risk classification of the child. Seventy-six girls (age: 12.2+/-1.0 yr; height: 153.9+/-7.5 cm; body mass: 51.9+/- 15.5 kg; BMI: 21.7+/-5.4 kg/m2) participated in this investigation. LBIA measured %BF values were obtained immediately before and within 5-min after completing a structured, in-school, physical education class. Significant reductions (p < 0.001) in mean %BF (25.0+/-10.2 vs. 24.4+/ 10.3 %) were observed for the group following the physical education class. For the majority of the girls (88%), the %BF alteration was less than +/- 2.0 %BF. More specifically, the %BF magnitude of change was +/-1.0 %BF in 64.5% of the girls, between 1.1 and 2.0 %BF in 23.7% of the girls, and by more than 2.0 %BF in 11.8% of the girls. Regardless of the %BF magnitude of change, all girls remained in the same adiposity classification category (healthy vs. unhealthy body fat) following exercise. Adhering to the pre-test exercise guideline appears unnecessary when using LBIA to categorize the health risk of an adolescent girl. PMID- 27182339 TI - Longitudinal, Diet-induced Weight Gain is Associated with Increased Blood Monocytes and Reduced TLR4 Expression. AB - Excessive weight gain increases systemic inflammation resulting in increased disease risk. Toll-like receptor 4 (TLR4) reportedly mediates increases in inflammation; however, its role in obesity-induced inflammation has not been fully evaluated. The purpose of this study was to determine the longitudinal effect of diet-induced weight gain on blood monocyte concentration and cell surface TLR4 expression. Male CD-1 mice were randomly assigned to high-fat (HF, n = 12) or low-fat (LF, n = 13) groups. Non-lethal, saphenous vein blood samples were collected at 0, 4, 8 and 12 weeks of treatment. Three-color flow cytometry was used to measure monocyte (CD11b+/CD14+) concentration and TLR4 cell-surface expression. Data were analyzed with a repeated measures ANOVA; significance was set at P<0.05. Body weight at week 12 was 21% greater in HF than LF (P<0.05). At week 12 HF had 155% more monocytes (P<0.05) with 24% less TLR4 than LF; Monocyte concentration and body weight at week 12 was negatively correlated with TLR4 gMFI (P<0.05). The observed effects of high-fat feeding on blood monocytes are consistent with a phenotype, which may be associated with premature morbidity. The observed monocyte responses may be associated with immune dysfunction and diminished response to infection. PMID- 27182340 TI - Resistance and Aerobic Training Sequence Effects on Energy Consumption in Females. AB - The objective of this study was to investigate the effect of sequence of resistance and aerobic training on energy consumption on sedentary overweight females. Participants were 15 sedentary overweight females (age = 28.6 +/-12 yrs; BMI = 28.1+/-7.8) Subjects did a counterbalanced intervention: resistance training (circuit training) first (intervention RT) or aerobic exercise first (intervention AT), while oxygen consumption was continuously measured for 80 min. Subjects performed a warm-up on the treadmill at 40% of their heart rate reserve for 5 minutes, then for 30 minutes did continuous walking or jogging on the treadmill at ~67% of their predicted maximum heart rate reserve. Immediately following treadmill exercise, subjects performed 25 minutes of resistance exercises including 2 sets of 12 reps at 67% of their 1RM of each exercise. Cool down consisted of five minutes on the treadmill with a gradual decline in speed. The energy used during the AT intervention was 431.2 +/- 90.9 kcals compared to the RT intervention 398.3 +/- 93.9 kcals. The mean difference was significant, (p =0.003). Based on the results of this study, aerobic exercise preceding resistance training has a greater impact on total energy consumption in females versus the reverse order. PMID- 27182341 TI - The Impact of a Pilot Community Intervention on Health-Related Fitness Measures in Overweight Children. AB - The purpose of this study was to pilot a 5-week community-based intervention on improving measures of health-related fitness in overweight children. Data were obtained from 8 overweight and obese 8- to 14-year-old children. Measurements included muscular fitness (curl-ups and modified pull-ups), aerobic capacity (20 meter progressive aerobic cardiovascular endurance run [PACER] test), body composition (triceps and calf skinfolds), body mass index (BMI), and flexibility (back saver sit-and-reach). A significant reduction in BMI was observed at post test compared to baseline (P=0.03). There was a significant decrease in body fat at post-test for boys (P=0.013). PMID- 27182342 TI - A Phenomenological Investigation of Women's Experiences With Personal Training. AB - Personal training is a rapidly growing industry in a country that is in dire need of physical fitness and health improvements. The purpose of this phenomenological study was to better understand women's experiences with personal training. To address the research question, eight female participants ages 24 to 54 years were interviewed using the following phenomenological question: "When you think about your current experience with personal training what stands out for you?" The interviews were conducted, transcribed, and qualitatively analyzed to identify themes in participants' responses. The ground that emerged was positive experience within which existed four figural themes: Relationships, trainer qualities, outcomes, and motivation. Results reveal new insight for professionals in the fitness industry and provide future directions for research in kinesiology and exercise psychology. PMID- 27182343 TI - Exercise Science Academic Programs and Research in the Philippines. AB - In this invited editorial, professors from leading institutions in the Philippines, share information regarding their programs relating to Exercise Science. They have provided information on academic components such as entrance requirements, progression through programs, and professional opportunities available to students following completion; as well as details regarding funding available to students to participate in research, collaboration, and specific research interests. PMID- 27182344 TI - Type of Encouragement Influences Peak Muscle Force in College-Age Women. AB - To investigate if the type of encouragement during a maximal voluntary isometric contraction (MVIC) had an influence on peak muscle force in strength-trained versus untrained collegiate women. Eleven strength-trained (20+/-1 y) and twelve untrained (21+/-1 y) women participated in three, five-second MVICs of seated knee extension. The three trials consisted of verbal only encouragement, verbal + visual encouragement, and verbal + pain avoidance encouragement. In all three trials, the participants received the same verbal encouragement. Trials were counterbalanced to minimize any possible order effects. A repeated measure ANOVA was used to analyze data. Any significant main effects were further analyzed using Tukey post hoc tests. There was no interaction between training status and encouragement type for all subjects F(2,42) = 1.5474, p = 0.22). For all subjects, a main effect for encouragement type was detected (F(2,42) = 6.616, p <0.05) with significant differences found in MVIC between the verbal encouragement and verbal + visual feedback (99.5+/-29 ft-lbs and 115.6+/-29 ft lbs, p<0.01). No significant differences were found between the verbal only and the addition of pain avoidance (99.5+/-29 ft-lbs and 109.9+/-26.3 ft-lbs, p=0.069) or the visual and pain avoidance trials (115.6+/-29 ft-lbs and 109.9+/ 26 ft-lbs, p=0.43). In this study, training status did not significantly influence the response to type of encouragement. Individuals produced the most force during a MVIC with verbal and visual encouragement. The incorporation of verbal encouragement and visual feedback is an important factor in eliciting peak force in college-aged women. This may have important implications in training and rehabilitation models that incorporate resistive loading of the skeletal muscles. PMID- 27182345 TI - Riding position and lumbar spine angle in recreational cyclists: A pilot study. AB - This pilot study investigated the reliability of an inclinometer to assess lumbar spine angle in three different cycling positions, and explored the relationship between lumbar spine angle and riding position, anthropometry, bike measures and low back pain (LBP). Cyclists were recruited from two cycle clubs. Anthropometric variables and bike setup were measured before participants' bikes were secured in a wind trainer. Cyclists then adopted three positions for riding, upright on the handlebars, on the brake levers and on the drops, according to a random allocation. The angle of the lumbar spine was measured; using an inclinometer, at zero minutes and after cyclists had completed 10 minutes of cycling. Intra measurer reliability for inclinometer use to measure lumbar spine angle in each position was excellent (ICC=0.97). The angle of the lumbar spine changed significantly over 10 minutes in the brake position (p=0.004). Lumbar spine angle at 10 minutes was significantly different between the brake and drop positions (p=0.018, p<0.05), and between upright and drop positions (p=0.012, p<0.05). Lumbar spine angle was not related to anthropometric measures. The change in lumbar spine angle varied from one degree of extension to 12 degrees of flexion, with increased flexion occurring in 95% of trials. An inclinometer has excellent intra-measurer reliability to measure lumbar spine angle in cycling positions. Future research with a sample of 72 or more participants is required to determine if there is a significant relationship between LBP and lumbar spine angle in different cycling positions. PMID- 27182346 TI - An investigation of lower-extremity functional asymmetry for non-preferred able bodied walking speeds. AB - Functional asymmetry is an idea that is often used to explain documented bilateral asymmetries during able-bodied gait. Within this context, this idea suggests that the non-dominant and dominant legs, considered as whole entities, contribute asymmetrically to support and propulsion during walking. The degree of functional asymmetry may depend upon walking speed. The purpose of this study was to better understand the potential relationship between functional asymmetry and walking speed. Bilateral ground reaction forces (GRF) were measured for 20 healthy subjects who walked at nine different speeds: preferred, +10%, +20%, +30%, +40, -10%, -20%, -30%, and -40%. Contribution to support was determined to be the support impulse: the time integral of the vertical GRF during stance. Contribution to propulsion was determined to be the propulsion impulse: the time integral of the anterior-posterior GRF, while this force was directed forward. Repeated measures ANOVA (alpha = 0.05) revealed leg * speed interactions for normalized support (p = 0.001) and propulsion (p = 0.001) impulse, indicating that speed does affect the degree of functional asymmetry during gait. Post hoc comparisons (alpha = 0.05) showed that support impulse was approximately 2% greater for the dominant leg, relative to the non-dominant leg, for the -10%, 20%, and -40% speeds. Propulsion impulse was 12% greater for the dominant leg than for the non-dominant leg at the +20% speed. Speed does appear to affect the magnitude of bilateral asymmetry during walking, however, only the bilateral difference for propulsion impulse at one fast speed (+20%) was supportive of the functional asymmetry idea. PMID- 27182347 TI - The Association between Soft Drink Consumption and Body Fat in Females Age 16 to 24. AB - American soft drink consumption (SDC) has increased since the 1960's surpassing all other kinds of beverage consumption. In recent years, the scientific literature has suggested that SDC has been linked to the rising epidemic of obesity in children and adolescents. However, there is lack of information in scientific literature on the effects of SDC on body fat (BF%) in young females. The purpose of this study was to determine the association between SDC and BF% in young women, ages 16-24 years. Sixty-six females were asked to complete a 3-day food record, food frequency questionnaire, and an assessment BF% by dual-energy x ray absorptiometry (DXA). Overall, participants consumed 29.44 +/- 44.68 fl oz/day of soft drinks. There were significant positive associations between SDC and BF% (r = 0.24, p < 0.05). Due to the large standard deviation in SDC, secondary analysis compared moderate SDC (MSDC: < 32 fl oz/day) to high SDC (HSDC: >= 32 fl oz/day). Results suggested HSCD had significantly greater BF% than MSDC. Therefore, limiting the consumption of soft drinks is suggested in order to maintain a healthy BF%. PMID- 27182348 TI - Racial/Ethnic Differences in Bone Mineral Density of Young Adults. AB - An estimated 1.5 million people suffer a bone disease-related fracture every year. Most work investigating bone mineral density (BMD) focuses on post menopausal females but a report from the Surgeon General in 2004 stated that of particular concern are men, racial and ethnic minorities, poor individuals, individuals with disabilities, and individuals living in rural areas. The purpose of this study was to examine the racial/ethnic differences in bone mineral density of young adults and to investigate any correlations with variables suggested to influence BMD. BMD was assessed at a younger age than most studies based on the assumption that osteoporosis is a pediatric disorder that manifests in old age. Whole-body BMD, percent body fat (BF), fat mass (FM), and lean mass (LM) of 103 college-aged Blacks, Whites, and Hispanics (18 - 34 years of age) were measured using a Lunar Prodigy Dual Energy X-ray Absorptiometry (DEXA). Blacks and Whites were taller than Hispanics. Blacks had higher BMD than Whites and Hispanics. Blacks and Whites had higher t-scores than Hispanics. Weight and LM correlated with BMD for all three groups. Height correlated with BMD for Blacks only. FM correlated with BMD for Hispanics only. In conclusion, BMD is suggested to be higher in Blacks than Whites and Hispanics. LM is suggested to be an important component of bone health. It is important to stress resistance training for building and maintaining bone health throughout life. PMID- 27182349 TI - Challenging the Accuracy of a Single-test Lactate Threshold Protocol in Collegiate Rowers. AB - : Elite rowers use lactate threshold (LT) estimates as a basis for training intensity in order to achieve the greatest training volume. For convenience, LT is usually determined in a maximal LT/VO2max test. This simultaneous test is problematic because it requires a large power increment, which may not give the most accurate LT. PURPOSE: To challenge the validity of a simultaneous LT/VO2max test to estimate LT in rowers. METHODS: Collegiate rowers (n=20, 16F and 4M, age 19.3+/-1.3 years, height 171.5+/-7.1 cm, weight 70+/-14 kg, VO2max 44.6+/-5.5 ml*kg-1*min-1) performed two LT tests. Participants completed an incremental VO2max test with 3-minute intervals increasing by 30W and 40W for women and men respectively. The second test consisted of five 6-minute stages of 10W increments starting from 20W below the estimated LT. For both tests, blood lactate was measured at the end of each stage and LT was determined by the lactate deflection point. The difference in intensity between the first deflection point and the LT was then calculated. RESULTS: Average difference between LT1 and LT2 was 1.15 +/- 13.4W, and were not statistically different (p=0.204). Average absolute difference was 9.95 +/- 8.80W, and was different from the average (p=0.022). CONCLUSION: A second incremental test should be performed for the most precise determination of LT. This is particularly important to rowers who rely on LT to determine training intensities. PMID- 27182351 TI - Evaluation of Metabolic Stress between Jumping at Different Cadences on the Digi Jump Machine. AB - The American College of Sports Medicine (ACSM) recommends that healthy adults achieve a minimum of thirty minutes of moderate intensity aerobic exercise five days per week. While cycling, walking, and jogging are commonly observed methods of achieving these recommendations, another option may be repetitive jumping. The purpose of this study was to examine the metabolic responses between repetitive jumping at a cadence of 120 jumps per minute (JPMs) vs. 100 JPMs when utilizing the Digi-Jump machine. Twenty-eight subjects completed two jumping trials, one at 120 JPMs and one at 100 JPMs. Subjects jumped until volitional exhaustion, or for a maximum of fifteen minutes. Oxygen uptake (VO2), heart rate (HR), respiratory exchange ratio (RER), and rating of perceived exertion (RPE) were assessed each minute of each exercise trial. RPE was differentiated, in that subjects reported perceived exertion of their total body, their upper-leg, and their lower leg. Results of this study indicated that there was no significant difference between the two trials for VO2, HR, or total body RPE. Differences were reported between trials for peak and average RER, with the 120 JPM trial eliciting a lower RER for both (peak: 1.08 +/- .087 vs. 1.17 +/- .1 p=.000; average: .99 +/- .076 vs. 1.04 +/- .098 p=.002), peak upper leg RPE (120: 15.29 +/- 3.89 vs. 100: 16.75 +/- 2.52 p=.022), and average lower leg RPE (120: 15.04 +/- 2.55 vs. 100: 13.94 +/- 2.02 p=.019). Also, there was a significant difference in exercise duration between the trials, with subjects able to exercise longer during the 120 JPM trial (12.4 +/- 3.42 mins vs. 9.68 +/- 4.31 mins p=.000). These data indicate that while the physiological stress may not be different between the two trials as indicated by VO2 and HR, the 120 JPM trial appears less strenuous as evidenced by RER values and by subjects' ability to exercise longer at that cadence. PMID- 27182350 TI - Aerobic And Anaerobic Changes In Collegiate Male Runners Across A Cross-County Season. AB - The purpose of this study was to assess the physiological characteristics of trained NCAA Division III male runners across a competitive season of cross country. Eight male distance runners (age 20.6+/-1.4 y) were administered a battery of aerobic and anaerobic laboratory tests at the beginning and end of an 8-10 week racing season. Aerobic testing included maximal oxygen uptake (VO2max), running economy (RE), ventilatory threshold (VT) and the onset of blood lactate accumulation (OBLA). Anaerobic testing consisted of the vertical jump (VJ) and the Wingate test. Final testing revealed anaerobic Wingate peak power significantly declined (11.8+/-1.1 to 10.7+/-1.0 W.kg-1) (P = 0.006), while no significant changes were seen in VJ or any aerobic parameters (P > 0.05). These results indicate that a competitive cross-country season of training and racing diminished anaerobic peak power and failed to elicit quantifiable aerobic adaptations in previously trained collegiate distance runners. PMID- 27182352 TI - The International Journal of Exercise Science: 2010 Year in Review. PMID- 27182353 TI - Analysis of Heel Raise Exercise with Three Foot Positions. AB - Prior research revealed activation differences between the medial (MG) and lateral (LG) gastrocnemius when performing heel raise exercise with neutral (N), internally-rotated (IR) and externally-rotated (ER) foot positions. Studying underlying biomechanics may help explain activation differences. The purpose was to compare ankle (AN), knee (KN), and hip (HI) contributions (initial joint angles) to attaining each initial foot position, ankle flexion-extension range of motion, ankle mechanical energy expenditure, repetition time, and percent cycle concentric-eccentric transition between N, IR, and ER foot positions. Twenty healthy subjects (11 male, 9 female) with resistance training experience performed twelve repetitions of free-weight (135% body mass) heel raise exercise using N, IR and ER foot positions in a counterbalanced order. Forefeet were elevated .05m onto separate forceplates. Electromagnetic sensors secured along dominant lower limb recorded kinematic data. Dependent variables were averaged across five selected repetitions. No significant differences existed for repetition time (P=.209), percent cycle concentric-eccentric transition (P=.668), ankle mechanical energy expenditure (P=.590), and ankle flexion-extension range of motion (P=.129) between foot positions. Post hoc comparison of a significant joint by foot position interaction (P<.001) demonstrated IR>N>ER for the initial HI and KN angles, whereas for AN, ER>IR and N. Between joints: AN 0.05). In conclusion, both interventions appear to improve function and knee stability among persons with symptomatic knee OA. As KBA has never been studied as an independent treatment program, our results indicate it is a promising stand-alone intervention worthy of further study. PMID- 27182360 TI - A Description of Variability of Pacing in Marathon Distance Running. AB - The purpose of this study was twofold: 1) to describe variability of pacing during a marathon and 2) to determine if there is a relationship between variability of pacing and marathon performance. Publically available personal global positioning system profiles from two marathons (Race 1 n = 116, Race 2 n = 169) were downloaded (http://connect.garmin.com) for analysis. The coefficient of variation of velocity (Velcov) was calculated for each profile. Each profile was categorized as finishing in under 3.9 hours, between 3.9 and 4.6 hours, or longer than 4.6 hours. Linear and quadratic lines of best fit were computed to describe the relationship between marathon finish time and Velcov. A 2 (Race) * 3 (bin) analysis of variance (ANOVA) was used to compare the dependent variable (Velcov) between races and the marathon bin finish times. Velcov was not influenced by the interaction of finish time bin and Race (p>0.05) and was not different between races (Race 1: 16.6 +/- 6.4%, Race 2: 16.8 +/- 6.6%, p>0.05). Velcov was different between finish time categories (p<0.05) for each race such that Velcov was lower for faster finish times. Using combined data from both races, linear (marathon finish time = marathon finish time = 0.09Velcov + 2.9, R^2 = 0.46) and quadratic (marathon finish time = -0.0006 Velcov 2 + 0.11 Velcov + 2.7, R^2 = 0.46) lines of best fit were significant (p<0.05). Slower marathon finishers had greater variability of pace compared to faster marathoner finishers. PMID- 27182361 TI - Does the Friel Anaerobic Threshold Test Accurately Detect Heart Rate Deflection in Trained Cyclists? AB - : The Friel Anaerobic Threshold Test (FATT) has been used to determine anaerobic threshold (AT). The FATT suggests AT occurs near the heart rate deflection point (HRDP) at a rating of perceived exertion (RPE) of 17. PURPOSE: The primary purpose of this study was to determine 1) whether the HRDP could be determined using the FATT, 2) examine differences between HRVT and HR that coincided Borg's rating of perceived exertion (RPE) of 17, and 3) if riding position (hoods or aero) would influence performance. METHODS: Fourteen male cyclists (30.4 +/- 7.41years of age; 151.8 +/- 60.4 cycled miles/week) participated in the study. Each subject performed the FATT on two occasions within one week. RESULTS: The findings of this study suggest that the FATT can determine HRDP in trained cyclists while riding in the hoods position but not the aero position. No significant difference was found between the hoods and aero position for HRVT as measured by the metabolic cart. Our data suggest that HR at an RPE of 15 more accurately reflects the HRVT than the RPE of 17. A low, non-significant correlation was found for both the hoods and aero (0.41 and 0.44, respectively; p > 0.20) for the HR at RPE of 17. CONCLUSION: The findings of this study suggest that the FATT can determine HRDP in trained cyclists. However, HRDP was identified in the cyclists preferred riding position. When performing the FATT, HRVT at an RPE of 15 should be used to estimate VT over the suggested RPE of 17. PMID- 27182362 TI - Presence of Observers Increases One Repetition Maximum in College-age Males and Females. AB - PURPOSE: To determine if the presence of observers affects muscular strength performance in college-age males and females. METHODS: Twenty-five women and 24 men participated in the study. Two counter-balanced trials were performed in which participants completed 1-RM tests in bench press and leg press. During one trial, two members of the opposite gender observed the 1-RM tests. During the other trial there were no observers, other than the tester. RESULTS: 1-RM for females increased 3.4+/-0.8 lbs on bench press (p<.001) and increased 9.2+/-3.8 lbs on leg press (p=.025) when observers were present. 1-RM for males increased 4.2+/-1.1 lbs on bench press (p=.001) and increased 18.8+/-5.2 lbs on leg press (p=.002) with observers present. There was no difference in the percent increase in 1-RM between males and females for either leg press (p=.71) or bench press (p=.08). CONCLUSION: College-age males and females lifted more weight during a 1 RM test when observers were present. PMID- 27182364 TI - Case Study on the Development of the International Journal of Exercise Science. PMID- 27182363 TI - Lymphocyte Apoptosis in Smokers and Non-Smokers Following Different Intensity of Exercises and Relation with Lactate. AB - Purposes of this study were 1) to examine the exercise intensity where lymphocyte apoptosis index (AI) is significantly increased in smokers and non-smokers, 2) to find out whether AI is associated with level of lactate (L). Fourteen healthy untrained smokers (<= 1 pack year, n=7) and non-smokers (n=7) aged 18 to 26 were recruited. Each subject conducted three treadmill runs at different intensities randomly. Running distance for all three runs was equivalent to 30 minute run at 70% VO2max. AI and L were analyzed at rest (Pre), immediately after (Post), and 1 h following (1 h post) each run. Data was analyzed using two way repeated measures ANOVA. Smokers showed higher AI than non-smokers at Post in 60% (12.5+/ 0.62% vs. 9.97+/-0.51, p<.008) and 70% VO2max running trials (17.53+/-0.57% vs. 15.6+/-0.41, p<.018). All L values at post showed significantly higher than Pre and 1 h post, but there was no significant difference between smokers and non smokers. The strong positive relationship between AI and L was detected (r=.739, smokers vs. r=.793, non-smokers). Smokers tend to have higher AI than non-smokers following runs at 60% and 70% VO2max, but not following a run at 80% VO2max. An increase in AI following a run at 60% VO2max indicates that lymphocyte apoptosis can be increased following moderate intensity exercise. Since L and AI at post were increased in dose-dependent manner to exercise intensity, it is suggested that an increase in lactate production during exercise might contribute to the increase in lymphocyte apoptosis. PMID- 27182365 TI - Outcomes of a Family Based Pediatric Obesity Program - Preliminary Results. AB - Children that are classified as obese (body mass index (BMI) > 95th percentile for age and sex, Centers for Disease Control and Prevention) have an increased risk for metabolic and cardiovascular complications. Family based programs that focus on physical activity (PA) and healthy eating are recommended for treatment of pediatric obesity. The purpose of the current study is to determine the outcomes of Building Healthy Families (BHF), a family-based pediatric weight loss treatment program composed of nutrition, physical activity and behavioral modification strategies. In addition, mediating variables that are associated with weight loss in children, in order to enhance the retention and success of this program will be identified. Twenty-two obese (>95th percentile BMI) children (age: 9.94 +/- 1.58 yrs) volunteered to participate. Children and their parents (20 moms, 20 dads, 68% obese; BMI > 30 kg.m-2) participated in weekly nutrition education, family lifestyle PA, and one-on-one meetings with a behavioral psychologist. Overall, child participants lost an average of 2.3 +/- 2.0 kg of body mass in 12 weeks while parents lost 6.4 +/- 4.3 kg of their body mass. There was a significant inverse association between percentage of program goals met and weight loss (r = - 0.67, p < 0.05). Decreases in the child participants intake of high fat, high calorie foods significantly predicted weight change (R2=0.98, p<0.05). In conclusion, family based pediatric obesity programs may offer significant benefits and lead to healthier lifestyles for obese children and their parents. PMID- 27182366 TI - Repeated Sprint Performance in Male and Female College Athletes Matched for VO2max Relative to Fat Free Mass. AB - The purpose of this study was to examine gender differences in repeated sprint exercise (RSE) performance among male and female athletes matched for VO2max relative to FFM (VO2max FFM). Thirty nine male and female college athletes performed a graded exercise test for VO2max and hydrostatic weighing to determine FFM. From the results, 11 pairs of males and females matched for VO2max FFM (mean +/- SD; 58.3 +/- 4.3 and 58.9 +/- 4.6 ml.kg FFM-1.min-1; men and women, respectively) were identified. On a separate day, matched participants performed a RSE protocol that consisted of five 6-sec cycle sprints with 30-sec recovery periods, followed by 5-min active recovery and a 30-sec all-out sprint. Repeated 6-sec sprint performance did not differ between men and women; both maintained power output (PO) until sprint 4. POFFM (W.kg-1 FFM) did not differ between men and women during the five sprints. During the 30-sec sprint, men achieved a lower peak POFFM than women (11.7 +/- 1.5 vs 13.2 +/- 1.2); however, the decline in POFFM over 30 sec was greater in women. VO2 (ml.kg FFM-1.min-1) was lower in men during recovery (24.4 +/- 3.8 vs 28.7 +/- 5.7) and at the beginning (29.2 +/- 4.0 vs 34.7 +/- 4.9) and end (49.4 +/- 5.0 vs 52.3 +/- 4.0). of the 30-sec sprint. These data indicate that men and women with similar aerobic capacities do not respond differently to short repeated sprints but may differ in their ability to recover and perform sprints of longer duration. PMID- 27182367 TI - Do exergames allow children to achieve physical activity intensity commensurate with national guidelines? AB - The purpose of this study was to determine if two popular exergames, Wii FitTM and EA Sports ActiveTM, both games for the Nintendo WiiTM console, help children achieve intensity consistent with recommended physical activity guidelines. Thirty children (19 males and 11 females, Mean age = 9.4 +/- 1.8 years) participated in this study by playing each game during one research session. During the session participants wore a heart rate monitor and accelerometer to measure exercise intensity. Perceived exertion (RPE) was measured with the children's run/walk OMNI scale. All three measures of exercise intensity (heart rate, accelerometer counts, and RPE) found that the EA Sports ActiveTM game session elicited higher exercise intensity. However, heart rate data found both games to achieve moderate intensity (65-68% age-predicted HRmax). When using heart rate as an indicator of exercise intensity it appears that both exergames were of sufficient intensity to achieve physical activity guidelines. Future studies should continue to investigate the utility of exergaming in helping children to become more physically active. PMID- 27182368 TI - Influence of Differences in Exercise-intensity and Kilograms/Set on Energy Expenditure During and After Maximally Explosive Resistance Exercise. AB - With resistance exercise, greater intensity typically elicits increased energy expenditure, but heavier loads require that the lifter perform more sets of fewer repetitions, which alters the kilograms lifted per set. Thus, the effect of exercise-intensity on energy expenditure has yielded varying results, especially with explosive resistance exercise. This study was designed to examine the effect of exercise-intensity and kilograms/set on energy expenditure during explosive resistance exercise. Ten resistance-trained men (22+/-3.6 years; 84+/-6.4 kg, 180+/-5.1 cm, and 13+/-3.8 %fat) performed squat and bench press protocols once/week using different exercise-intensities including 48% (LIGHT-48), 60% (MODERATE-60), and 72% of 1-repetition-maximum (1-RM) (HEAVY-72), plus a no exercise protocol (CONTROL). To examine the effects of kilograms/set, an additional protocol using 72% of 1-RM was performed (HEAVY-72MATCHED) with kilograms/set matched with LIGHT-48 and MODERATE-60. LIGHT-48 was 4 sets of 10 repetitions (4*10); MODERATE-60 4*8; HEAVY-72 5*5; and HEAVY-72MATCHED 4*6.5. Eccentric and concentric repetition speeds, ranges-of-motion, rest-intervals, and total kilograms were identical between protocols. Expired air was collected continuously throughout each protocol using a metabolic cart, [Blood lactate] using a portable analyzer, and bench press peak power were measured. Rates of energy expenditure were significantly greater (p<=0.05) with LIGHT-48 and HEAVY 72MATCHED than HEAVY-72 during squat (7.3+/-0.7; 6.9+/-0.6 > 6.1+/-0.7 kcal/min), bench press (4.8+/-0.3; 4.7+/-0.3 > 4.0+/-0.4 kcal/min), and +5min after (3.7+/ 0.1; 3.7+/-0.2 > 3.3+/-0.3 kcal/min), but there were no significant differences in total kcal among protocols. Therefore, exercise-intensity may not effect energy expenditure with explosive contractions, but light loads (~50% of 1-RM) may be preferred because of higher rates of energy expenditure, and since heavier loading requires more sets with lower kilograms/set. PMID- 27182370 TI - The International Journal of Exercise Science: 2011 Year in Review. PMID- 27182369 TI - The effect of exercise mode and intensity of sub-maximal physical activities on salivary testosterone to cortisol ratio and alpha-amylase in young active males. AB - We examined the effect of exercise intensity and mode on the acute responses of free testosterone to cortisol ratio and salivary alpha-amylase. We also evaluated the relationship between cortisol and salivary alpha-amylase. Ten healthy young active males participated voluntarily in this study in six single sessions. They exercised on a cycle ergo meter, treadmill, and elliptical instrument at intensities of 70% and 85% maximum heart rate for 25 minutes. Saliva samples were collected 5 minutes before and 5 minutes after each exercise session. No significant changes were observed for cortisol. Free testosterone to cortisol ratio increased during each exercise session (F5, 45=3.15, P=0.02). However, these changes are only significant after exercise on the treadmill at 70% maximum heart rate (t=2.94, P=0.02) and 85% maximum heart rate (t=0.53, P=0.03). Salivary alpha-amylase significantly varied among exercise sessions (F5, 45=3.97, P=0.005), and a significant decline was observed after exercise on the elliptical instrument (t=2.38, P=0.04) and treadmill (t=3.55, P=0.006) at 85% maximum heart rate. We found that the free testosterone to cortisol ratio is dependent on the exercise mode, while the salivary alpha-amylase response is dependent on the intensity of exercise. The increase of free testosterone to cortisol ratio in this study may indicate lower physiological stress in response to performing these exercises. Applying muscular strength with moderate intensity weight bearing exercises possibly activates the anabolic pathways. Although the cortisol and salivary alpha-amylase responses were opposite in the majority of the exercise sessions, no significant inverse relationship was observed. PMID- 27182371 TI - FITNESSGRAM(r) Friday: A Middle School Physical Activity and Fitness Intervention. AB - Texas Senate Bill 530 (2007) mandated fitness assessment as part of the annual K 8 Physical Education (PE) curricula, yet no studies have reported interventions designed to improve and quantify individual student passing rates or individual school performance. Students (Total 2008-2010 N=1484; 729 females, 755 males; mean age = 11.85 y; mean BMI = 22.69 or > 90%-tile, overweight) were evaluated on individual FITNESSGRAM(r) performances in a cross-sectional analysis of 6th graders comparing baseline scores (year 1) with outcomes of a physical activity intervention in years 2 and 3. Students participated in regular PE classes (including campus wellness center activities) with a once a week focus (FITNESSGRAM(r) Friday) on improving mile run scores and other assessment scores. Students significantly improved FITNESSGRAM(r) scores following the PE intervention to levels similar to state reported averages. On average, boys improved their pushups by 32.7%, trunk lift by 17.4% and mile run times by 29.5%. Averages for girls improved by 15.4% for pushups, 6.7% for truck lift, and by 38.6% for the mile run. The percentage of boys in our study achieving all six FITNESSGRAM(r) tests in the HFZ was 3% at baseline and 22% following intervention. The percentage of girls meeting the criteria for the HFZ on all six FITNESSGRAM(r) tests was 4.5% at baseline and 20% following intervention. This study provides a potential model for fitness success in other middle school PE interventions, in Texas and the nation. PMID- 27182372 TI - Stability Ball Sitting versus Chair Sitting During Sub-maximal Arm Ergometry. AB - : It was predicted that sitting on a stability ball during arm ergometry would elevate cardiovascular parameters when compared to sitting on a chair and that this would be associated with greater recruitment of trunk and leg skeletal muscles. METHODS: Open-circuit spirometry, videotaping, blood pressure, heart rate, and EMG were conducted during rest and four minute stages of 15 W, 30 W, and 45 W using a Monark arm ergometer. Twenty-six apparently healthy adults exercised twice, once sitting on a stability ball and the other sitting on a chair (order randomized), with 45 to 60 minutes of rest between. ANOVA for repeated measures and paired-t testing were used for analysis. RESULTS: Oxygen consumption was significantly 10 to 16% higher during exercise while sitting on the stability ball. There were no significant differences between sitting modes for heart rate, SBP, and DBP. Also, resting and exercise rectus femoris and 45 W external oblique EMGs were significantly higher on the stability ball. Finally, the knee was significantly more extended with the feet farther apart and more forward on the stability ball. CONCLUSION: The stability ball significantly elevates oxygen consumption during sub-maximal arm cranking without significantly increasing heart rate or blood pressure and this is associated with increased thigh muscle activation and lower leg repositioning. PMID- 27182373 TI - The Effects of Muscle Mass on Homocyst(e)ine Levels in Plasma and Urine. AB - The present study was designed to examine the relationship between homocyst(e)ine (H[e]) levels and muscle mass. Two experimental groups each of 24 Caucasian males, one consisting of higher-muscle mass subjects (HMM) and the other of lower muscle mass subjects (LMM) participated in this study. Muscle mass was estimated from 24-hour urine collections of creatinine (Crt). Muscle mass was 40.3 +/- 15.9 kg in HMM and 37.2 +/- 11.4 kg in LMM (P= 0.002). Mean plasma H(e) levels in HMM were 10.29 +/- 2.9 nmol/mL, and in LMM were 10.02 +/- 2.4 nmol/L (Not significant, [NS]). Urinary H(e) levels (UH[e]) were 9.95 +/- 4.3 nmol/mL and 9.22 +/- 2.9 nmol/mL for HMM and LMM, respectively (NS). Plasma H(e) levels correlated well with UH(e) (HMM: r= 0.58, P= 0.009; LMM: r= 0.66, P= 0.004). Muscle mass and was not correlated to either plasma H(e) or UH(e). However, in HMM trends were identified for body mass to be correlated with UH(e) (r= 0.39, P= 0.10) and UCrt (r= 0.41, P= 0.08). Surprisingly, in HMM plasma and UCrt were only weakly correlated (r= 0.44, P= 0.06). Our results do not support a causal relationship between the amount of muscle mass and H(e) levels in plasma or urine. PMID- 27182374 TI - Effects of Carbohydrate-Protein Ingestion Post-Resistance Training in Male Rugby Players. AB - Evidence suggests that carbohydrate-protein (CHO-PRO) drinks post-exercise are an advantageous nutritional recovery intervention. Resistance trained (n = 14, mean +/- SD; age 19 +/- 1 yr, mass 95 +/- 9 kg, % fat 17 +/- 4 % and BMI 28.5 +/- 1.8 kg.m-2) male rugby players participated in a study investigating effects of carbohydrate (CHO) and CHO-PRO drinks on subsequent resistance exercise performance. Following an initial resistance training (RT) protocol consisting of 8 circuits of 5 discrete exercises at 10 repetition maximum (RM), participants received 10 mL.kg-1 BM of randomised sports drink (LCHO, HCHO and CHO-PRO) on completion of the RT protocol and at 120 min into a 240 min recovery period. Post recovery, participants completed a test to failure (TTF) protocol performing as many circuits of the same exercises at 10-RM to failure. Individual exercise cumulative load (?W) lifted and total work capacity (TWC) for each trial was recorded. Both ?W and TWC were normalised for body mass (kg.kg-1 BM). Data were analysed using repeated measures ANOVA with post-hoc Student-Neuman-Keuls pair wise comparisons (P<0.05). Despite large intra-subject variability between trials, TWC normalised for body mass was significantly greater following CHO-PRO compared with HCHO and LCHO (188 +/- 26 vs. 157 +/- 21 and 150 +/- 16 kg.kg-1 BM, respectively; P<0.05). The ?W lifted after ingestion of HCHO and LCHO were not significantly different despite differing CHO and caloric content. The CHO-PRO induced enhancement of recovery was possibly due to higher rates of glycogen restoration after the initial glycogen depleting RT protocol. PMID- 27182375 TI - Experimentally Manipulated Somatic Information and Somatization Tendencies and their Impact on Physical Symptom Reporting and Performance in a Physically Strenuous Task. AB - This study attempts to determine whether the presentation of an experimentally manipulated somatic experience during a physically strenuous task can influence physical performance and symptom reporting. The study also compares the relative influence of experimentally manipulated somatic information (state somatization) with stable individual differences in the tendency to amplify physical symptoms (trait somatization) on performance and symptom reporting. 194 participants completed standardized measures of somatization tendencies, state anxiety, neuroticism and conscientiousness. Participants where then given a mock physical exam, with individuals randomly assigned to receive either favorable or unfavorable somatic information. All participants then had their body mass index assessed and completed a rigorous exercise task, with quantification of performance. Physiological measures of blood pressure and pulse were also assessed before and after the exercise task. The experimentally manipulated presentation of somatic information predicted both performance and physical symptoms, even after controlling for BMI, neuroticism, conscientiousness, and state anxiety. Moreover, expected performance uniquely and significantly predicted performance above and beyond condition, anxiety, BMI, neuroticism, and conscientiousness. Somatosensory amplification tendencies also predicted symptom endorsement, but not performance. Findings suggest that both state and trait expectations with respect to somatic experiences influence symptom reporting and to a lesser extent performance, even after controlling for variables known to strongly influence each of these outcomes. Results are consistent with the cognitive-perceptual and the cognitive-appraisal models of somatic interpretation. PMID- 27182376 TI - Self-estimation of Body Fat is More Accurate in College-age Males Compared to Females. AB - The objective was to determine the effect of gender on the ability to accurately estimate one's own body fat percentage. Fifty-five college-age males and 99 college-age females participated. Participants estimated their own body fat percent before having their body composition measured using a BOD POD. Participants also completed a modified Social Physique Anxiety Scale (SPAS). Estimated body fat was significantly lower compared to measured body fat percent in females (26.8+/-5.6% vs. 30.2+/-7.0%, p<0.001) but not in males (16.8+/-6.8% vs. 18.1+/-8.3%, p=0.09). The mean difference between estimated and measured body fat was significantly higher for females compared to males (p<0.001). There was a moderate, significant correlation found between measured body fat percent and SPAS score for males (r=0.331, p=0.014) and females (r=.427, p<0.001). Males estimated their body fat percent more accurately than females. Despite these findings, 62% of males and 76% of females underestimated their body fat. PMID- 27182378 TI - Research and Critical Thinking : An Important Link for Exercise Science Students Transitioning to Physical Therapy. AB - Critical thinking skills are increasingly necessary for success in professional health care careers. Changes in the contemporary healthcare system in the United States arguably make these critical thinking skills more important than they have ever been, as clinicians are required on a daily basis to evaluate multiple bits of information about patients with multiple-systemic health concerns and make appropriate treatment decisions based on this information. We believe the IJES, with its emphasis on engaging undergraduate and graduate students in research and scholarly activity, is a valuable resource for promoting the higher-order critical thinking skills necessary for preparing exercise science students with an interest in professional healthcare careers such as physical therapy. PMID- 27182377 TI - Physiological and Perceptual Responses to Nintendo(r) Wii FitTM in Young and Older Adults. AB - Physically active video gaming (AVG) provides a technologically-modern, convenient means of increasing physical activity (PA). This study examined cardiovascular, metabolic, and perceptual responses in young adult (AP) and older adult (OP) participants engaging in Wii FitTM AVG play, and compared PA levels during play to recommended PA levels. Heart rate (HR), percent heart rate reserve (%HRR), oxygen consumption (VO2), energy expenditure (EE), rating of perceived exertion (RPE), enjoyment level (EL), and step count data were obtained from 10 YP and 10 OP during 15 minutes of rest and four 15-minute bouts of Wii FitTM activities (yoga, balance, aerobics, strength). For all participants, AVG significantly increased HR, VO2, and EE measures above rest, with significant between-activity differences. Responses were similar between YP and OP, except that the activities were more intense for OP, in terms of %HRR and RPE. Most games elicited responses consistent with light-intensity PA, though peak HR and VO2 values for aerobic and strength games met or approached recommended PA intensities. Wii FitTM appears to provide an enjoyable form of light PA for both YP and OP, which can reduce inactive screen time and provide beneficial cardiovascular, musculoskeletal, and metabolic stimulation. PMID- 27182379 TI - Differences in Force-velocity Characteristics of Upper and Lower Limbs of Non competitive Male Boxers. AB - Despite the increasing popularity of boxing, only a few studies have been conducted on the physiology or the biomechanics of this sport. The aim of the present study is to examine the ratios of mechanical characteristics (maximal anaerobic power, Pmax, theoretical maximal force, F0, and velocity, v0) between upper and lower limbs of male boxers. Twelve male caucasians, all members of a local fitness club, aged 29.5 (3.2) yr [mean (standard deviation)], stature 1.74 (.05) m, body mass 77.9 (8.1) kg, body fat 22.4 (3.9) % and somatotype 5.5-5.5 1.1, performed a force-velocity (F-v) test for both legs and arms. The F-v test included five supramaximal pedal sprints, each lasting 7 sec, against incremental braking force of 20-60 N for arms and 30-70 N for legs, on modified arm-cranking and on cycle ergometer (Ergomedics 874, Monark, Sweden). The legs had higher Pmax (910 W vs. 445 W, t11=22.9, p<.001), Pmax expressed in relative to body mass values (rPmax, 11.8 W.kg-1 vs. 5.8 W.kg-1, t11=20.6, p<.001), F0 (168 N vs. 102 N, t11=21.7, p<.001), v0 (217 rpm vs. 177 rpm, t11=46.6, p<.001) and lower v0/F0 (1.33 rpm.N-1 vs. 1.82 rpm.N-1, t11=15.3, p<.001) than the arms. Pmax of upper limbs was associated with Pmax of lower limbs (r=.70, p<.05) and their ratio was .49 (.06). The respective values of rPmax was r=.76 (p<.01), F0, r=.35 (p=.26) and .61 (.13), and of velocity, v0, r=.17 (p=.59) and .812 (.10). In spite of moderate associations between upper and lower limbs' F0 and v0, a stronger relationship was found with regard to Pmax. These findings emphasize the need for separate evaluation of arms' and legs' F-v characteristics on a regular basis and the consideration of these measures in training design. PMID- 27182380 TI - Ground Reaction Forces Generated by Twenty-eight Hatha Yoga Postures. AB - Adherents claim many benefits from the practice of yoga, including promotion of bone health and prevention of osteoporosis. However, no known studies have investigated whether yoga enhances bone mineral density. Furthermore, none have estimated reaction forces applied by yoga practitioners. The purpose of this study was to collect ground reaction force (GRF) data on a variety of hatha yoga postures that would commonly be practiced in fitness centers or private studios. Twelve female and eight male volunteers performed a sequence of 28 hatha yoga postures while GRF data were collected with an AMTI strain-gauge force platform. The sequence was repeated six times by each study subject. Four dependent variables were studied: peak vertical GRF, mean vertical GRF, peak resultant GRF, and mean resultant GRF. Univariate analysis was used to identify mean values and standard deviations for the dependent variables. Peak vertical and resultant values of each posture were similar for all subjects, and standard deviations were small. Similarly, mean vertical and resultant values were similar for all subjects. This 28 posture yoga sequence produced low impact GRF applied to upper and lower extremities. Further research is warranted to determine whether these forces are sufficient to promote osteogenesis or maintain current bone health in yoga practitioners. PMID- 27182381 TI - Physiologic Responses, Liking and Motivation for Playing the Same Video Game on an Active Versus a Traditional, Non-Active Gaming System. AB - Evidence suggests that individuals playing certain video games on the Nintendo Wii(r) (Wii) exhibit increased energy expenditure versus traditional video games, although little research examines non-Wii Sports/Fit games. The purpose of this study is to assess physiologic responses, liking, and the relative reinforcing value (RRV) of a popular, non-Wii sports video game for the Wii relative to the same game played on a traditional, non-active system. Twenty-four college-aged students participated. Heart rate and oxygen consumption (VO2) was assessed during rest and when playing the following games: Madden NFL 2011(r) for Playstation 2 (PS2 Madden) and the Wii (Wii Madden), and Wii Sports Boxing. The RRV was assessed for Wii Madden versus PS2 Madden. Analysis of variance demonstrated a main effect for condition (p <= 0.01) as VO2 (5.2 +/- 0.2 ml.kg 1.min-1 Wii, 4.1 +/- 0.1 ml.kg-1.min-1 PS2, 3.7 +/- 0.1 ml.kg-1.min-1, rest) and heart rate (89.2 . 2.7 bpm Wii, 79.7 +/- 2.5 bpm PS2, 79.1 +/- 2.5 bpm, rest) was greater for Wii Madden than PS2 Madden and rest. Heart Rate (105.4 +/- 5.3 bpm) and VO2 (10.4 ml.kg-1.min-1) for Wii Sports Boxing was significantly greater than all other conditions (p <= 0.003). The RRV was not significantly different between Wii Madden and PS2 Madden (p = 0.50). Compared to the same game on a traditional system, Wii Madden is more physiologically challenging and equally reinforcing. However, Wii Madden would not be categorized as moderate-intensity physical activity. PMID- 27182382 TI - Actical Accelerometry Cut-Points for Quantifying Levels of Exertion: Comparing Normal and Overweight Adults. AB - Weight, body fatness and ambulatory pattern all have the potential to affect accelerometer output and cause differences in output between overweight and normal-weight adults. The purpose of this study was to determine if Actical (Philips Respironics, Bend, OR) activity count cut-points for moderate and vigorous intensity exercise are different for overweight adults compared to normal-weight adults. Overweight adults with BMI >25 kg/m2 (n=29) and Normal Weight adults (n=25) walked at 3.2 and 4.8 km.h-1 and ran at 6.4 km.h-1 on a treadmill while simultaneously wearing an Actical accelerometer and obtaining measurements of oxygen uptake. Counts per minute (counts.min-1) were determined at 3 METS (moderate) and 6 METS (vigorous) using ROC curves. The counts.min-1 at 3 METs was 1726 and 1923 counts.min-1 for Overweight and Normal-Weight groups, respectively. The cut-points at 6 METs were 4117 and 4032 counts.min-1 for Overweight and Normal-Weight groups, respectively. The differences between groups were not statistically significant (p>0.73 for both). Correlations between BMI and counts.min-1 were not significant (p>0.05) at any speed for the Normal-Weight group but were significant at 3.2 and 4.8 km.h-1 for the Overweight group. Although there appears to be some relationship between activity counts.min-1 and BMI, the results suggest that similar cut-points may be used for normal weight and overweight adults. However, the greater variability in counts at each speed and lower ROC curve areas for overweight adults suggest that it is harder to classify the activity intensity of overweight subjects compared to normal weight subjects. PMID- 27182383 TI - Validation of Three Body Composition Techniques with a Comparison of Ultrasound Abdominal Fat Depths against an Octopolar Bioelectrical Impedance Device. AB - The aims of this study were to cross-validate three clinical-grade measures of body composition, using an octopolar Bioelectrical Impedance (BIA), an ultrasound analyzer (US) and Air-Displacement Plethysmography (ADP) and second to compare the US scans of total abdominal, subcutaneous and visceral fat depths (mm) against the trunk percent fat (%BF) from the octopolar BIA. Twenty-six college aged (22.9 +/- 1.35 years) men (n = 18) and women (n = 8) volunteered to participate in this study. Body composition was assessed using BIA (total and by segments), ADP and US. In addition, total abdominal, subcutaneous and visceral fat layers were measured using the US. All measurements were done in accordance with manufacturers' guidelines. The %BF comparing the three clinical grade machines were all significantly correlated and no significant differences were found using a 1-way ANOVA. All three fat depths were significantly correlated to the trunk fat % via BIA, while significant differences were found for the 1-way ANOVA. A Tukey post-hoc test showed significant differences between the BIA trunk %BF and both subcutaneous and visceral US fat depths. Having valid ways to measure body composition and visceral fat that is accessible in terms of being transportable, cost effective, and simple to use, should become a part of preventive medicine. PMID- 27182384 TI - Energy Drinks: Ergolytic or Ergogenic? AB - Despite the growing popularity of energy drinks, many do not realize the negative effects on the cardiovascular system. The purpose of this study was to examine the effects of energy drink ingestion on estimated VO2max, heart rate (HR), systolic and diastolic BP (SBP and DBP, respectively), rate pressure product (RPP), and RPE at rest and during exercise. Seven healthy adults (age: 24.3 +/- 3.5 yrs; body mass: = 66.0 +/- 2.2 kg) participated in this randomized double blind, crossover study. Subjects ingested a placebo (PL) or Redline (RL) energy drink (240ml; 250 mg caffeine) 40 minutes before maximal graded exercise test (GXT). Estimated maximal oxygen consumption (VO2max) was lower in the RL trial (37.9+/-5.7 ml.kg-1.min-1) compared to the PL trial (39.7+/-6.5 ml.kg-1.min-1; P= 0.02). Although no significant differences were noted for the number of ectopic beats (ETB) between the trials, a five to one ratio for the RL and PL existed (RL = 106 total ectopic beats; PL = 21 total ectopic beats). Sub-maximal exercise heart demand (RPP: systolic BP * HR) at the same workload was considerably higher in the RL trial (224.9 +/- 39.9 mmHg.bts.min-1; P=0.04) compared to PL (195.8 +/- 22.9 mmHg.bts.min-1). Recovery DBP was significantly higher at one min. in the RL trial (51.6 +/- 25.1 mmHg) compared to PL (25.4 +/- 33.8 mmHg; P=0.05). Based on the results of this study, it was determined that energy drinks lowered estimated VO2max while elevating RPP and recovery DBP. PMID- 27182386 TI - Concurrent Verbal Encouragement and Wingate Anaerobic Cycle Test Performance in Females: Athletes vs. Non-Athletes. AB - To examine the effect of concurrent verbal encouragement on the performance of the WAnT in female athletes vs. female non-athletes. College-age female subjects were recruited where ten of the subjects were intercollegiate athletes (ATH, n1 =10) and the nine were non-athletes (NON, n2 =9). The WAnT was novel to all subjects and the subjects were blinded to the study's purpose. Prior to the experimental trials, subjects were measured for body composition and performed a familiarity WAnT trial without verbal encouragement. Subjects then performed the WAnT twice, once with concurrent verbal encouragement (VE) and once without (NVE), in a balanced cross-over design. Peak (PP) and mean power (MP), and total work (TW) were compared between ATH and NON across VE and NVE using an ANOVA (1 between, 1 within), alpha=0.05. ATH and NON did not differ (p>0.05) in age or body composition with the exception of fat-free mass which differed significantly (ATH=53.7+/-6.6, NON=46.1+/-5.7 kg) (p<0.05). A significant (p<0.05) main effect for ATH/NON was observed where ATH outperformed NON when pooled across VE/NVE trials for PP (ATH=13.0+/-1.4, NON=11.3+/-1.7 W.kg-1), MP (ATH=7.7+/-1.1, NON=6.7+/-0.9 W.kg-1) and TW (ATH=232+/-35, NON=201+/-26 J.kg-1). When pooled across all subjects (ATH and NON), the VE/NVE trials did not differ (p>0.05) for PP (VE=12.4+/-1.7, NVE=12.0+/-1.9 W.kg-1), MP (VE=7.3+/-1.1, NVE=7.2+/-1.2 W.kg 1) and TW (VE=219+/-33, NVE=215+/-35 J.kg-1). The ATH/NON interaction with VE/NVE was not significant (p>0.05). Concurrent verbal encouragement does not affect performance on the WAnT in females, nor does it affect WAnT performance in female athletes and non-athletes differently. PMID- 27182385 TI - Development and comparison of two field-based body fat prediction equations: NHANES 1999 - 2004. AB - Clinical guidelines define obesity in terms of excess body weight adjusted for height (i.e., bodymass index [BMI] categories) and/or gender-specific waist circumference (WC) cut-point values. Since body composition, particularly fat mass, is the most variable among individuals due to differences by gender, age, and race, and total percent body fat (%BF) can be estimated accurately using dual energy X-ray absorptiometry (DXA), the purpose of this study was to develop and compare two field-based body fat prediction equations suitable for a nationally representative sample of the US adult population. Data were analyzed from subjects 20+ years of age (n = 11,907) with BMI and WC values, and that participated in DXA scans as part of the 1999-2004 National Health and Nutrition Examination Survey (NHANES). Multiple linear regression was used to develop and compare DXA-estimated %BF as the dependent variable versus BMI or WC, gender, age, and race as predictor variables. Mean values for age, BMI, WC, and %BF among the sample were 46.84 +/- 0.30 years, 28.17 +/- 0.11 kg/m2, 96.69 +/- 0.27 cm, and 34.19 +/- 0.14 %, respectively. Both equations were similar in terms of explained variance, with R2 values of 0.82 for the BMI and WC equations, respectively. Both equations are easy to use, and could easily be developed as an application on a smartphone or other handheld device, or simply integrated into a spreadsheet for use as an additional tool for health professionals to assess the current health status of individuals based on predicted body fat from BMI, WC, and demographics. PMID- 27182388 TI - A Diabetic Adolescent Case Study: Use of a Website in Combination with an Exercise Program to Increase Physical Activity. AB - The purpose of this study was to report on the efficacy of a web-based technology support to encourage physical activity in children. This program was designed to promote physical activity and proper nutrition in the diabetic adolescent with a weekly meeting that consisted of a 30-minute educational session followed by 60- minutes of exercise. A specifically designed website was used as a support to this weekly supervised exercise program. Outcomes assessment included body mass index (BMI), muscle strength (grip strength, back and leg strength), flexibility, exercise self-efficacy, and physical activity participation (pedometer, LEAP II Survey). Improvements occurred in steps walked per day and exercise self-efficacy indicating that a once a week formal exercise, when combined with a technology support, is useful in increasing physical activity behavior. PMID- 27182389 TI - The Effects of a Short-Term Novel Aquatic Exercise Program on Functional Strength and Performance of Older Adults. AB - The purpose of this study was to determine the effects of a short-term novel multidimensional aquatic exercise program on functional abilities of healthy older adults. Twenty-six men and women (mean age 76.33 +/- 5.55 years) were recruited and assigned to an aquatic- (n = 15) or land-based (n = 11) training group. The aquatic training group completed a multidimensional water exercise program that incorporated resistance training, functional exercise movements and rudimentary aquatic plyometric activities. The active control group participated in a supervised land-based fitness program. Each exercise intervention was conducted over an 8-week period (16 sessions of 30 - 40 minutes) with the training load progression adjusted equally between groups using the 6 - 20 Rating of Perceived Exertion Scale (RPE). Prior to and immediately following the intervention, both groups were evaluated with select components of the Senior Fitness Test. The 30-second chair stand, 30-second arm curl, and 8 foot up and go were selected as measures of strength and functional abilities. The results of an independent t-test indicated that the control and experimental groups were matched for functional abilities prior to the intervention. A 2 (group) * 2 (time) analysis of covariance (ANCOVA) with repeated measures revealed significant differences in the pre- to post-testing measures for the aquatic training program for the arm curl (p < 0.01) and the 8 foot up and go (p = 0.02). Analysis of the active control revealed no pre-post differences for any measure. Thus, a short-term aquatic exercise program with multidimensional intervention strategies will significantly enhance functional abilities in older adults when compared to a functionally matched active control group. PMID- 27182387 TI - Nitric Oxide and the Biological Cascades Underlying Increased Neurogenesis, Enhanced Learning Ability, and Academic Ability as an Effect of Increased Bouts of Physical Activity. AB - The consummate principle underlying all physiological research is corporeal adaptation at every level of the organism observed. With respect to humans, the body learns to function based on the external stimuli from the environment, beginning in the womb, throughout the developmental stages of life. Nitric Oxide (NO) appears to be the governor of the plasticity of several systems in mammals implicit in their proper development. It is the purpose of this review to describe the physiological pathways that lead to plasticity of not only the vasculature but also of the brain and how physical activity plays a key role in those alterations by initiating the mechanism that triggers NO production. Further, this review hopes to show a connection between these changes and learning, comprising both motor learning and cognitive learning. This review will show how NO plays a significant role in vascularization and neurogenesis, necessary to enhance the mind-body connection and comprehensive physical performance and adaptation. It is our belief that this review effectively demonstrates, using a multidisciplinary approach, the causal mechanisms underlying the increases in neurogenesis as related to improved learning and academic performance as a result of adequate bouts of physical activity of a vigorous nature. PMID- 27182391 TI - Stroboscopic Training Enhances Anticipatory Timing. AB - The dynamic aspects of sports often place heavy demands on visual processing. As such, an important goal for sports training should be to enhance visual abilities. Recent research has suggested that training in a stroboscopic environment, where visual experiences alternate between visible and obscured, may provide a means of improving attentional and visual abilities. The current study explored whether stroboscopic training could impact anticipatory timing - the ability to predict where a moving stimulus will be at a specific point in time. Anticipatory timing is a critical skill for both sports and non-sports activities, and thus finding training improvements could have broad impacts. Participants completed a pre-training assessment that used a Bassin Anticipation Timer to measure their abilities to accurately predict the timing of a moving visual stimulus. Immediately after this initial assessment, the participants completed training trials, but in one of two conditions. Those in the Control condition proceeded as before with no change. Those in the Strobe condition completed the training trials while wearing specialized eyewear that had lenses that alternated between transparent and opaque (rate of 100ms visible to 150ms opaque). Post-training assessments were administered immediately after training, 10-minutes after training, and 10-days after training. Compared to the Control group, the Strobe group was significantly more accurate immediately after training, was more likely to respond early than to respond late immediately after training and 10 minutes later, and was more consistent in their timing estimates immediately after training and 10 minutes later. PMID- 27182390 TI - Kinematic Analysis of Four Plyometric Push-Up Variations. AB - Plyometric research in the upper extremity is limited, with the effects of open chain plyometric exercises being studied most. Kinematic and ground reaction force data concerning closed-chain upper extremity plyometrics has yet to be examined. Twenty-one recreationally active male subjects performed four variations of plyometric push-ups in a counterbalanced order. These included box drop push-ups from 3.8 cm, 7.6 cm, 11.4 cm heights, and clap push-ups. Kinematics of the trunk, dominant extremity and both hands were collected to examine peak flight, elbow flexion at ground contact, elbow displacement, and hand separation. Additionally peak vertical ground reaction force was measured under the dominant extremity. The 11.4 cm and clap push-ups had significantly higher peak flight than the other variations (P<.001). At ground contact, the elbow was in significantly greater flexion for the 3.8 cm and clap push-up compared to the other variations (P<.001). The clap push-up had significantly more elbow displacement than the other variations (P<.001) while hand separation was not significantly different between variations (P=.129). Peak vertical ground reaction force was significantly greater for the clap push-ups than for all other variations (P< .001). Despite similar flight heights between the 11.4 cm and clap push-ups, the greater peak vertical ground reaction force and elbow displacement of the clap push-ups indicates the clap push-up is the most intense of the variations examined. Understanding the kinematic variables involved will aid in the creation of a closed chain upper-extremity plyometric progression. PMID- 27182392 TI - Decreases in Maximal Oxygen Uptake Among Army Reserve Officers' Training Corps Cadets Following Three Months Without Mandatory Physical Training. AB - During the academic year, Army ROTC cadets are required to participate in mandatory physical training; however, during summer months training is not required. The purpose of this study was to determine if there is a change in cadet VO2max after the summer when training is not mandatory. Participants completed a graded exercise treadmill test to determine their VO2max in late spring of 2010 and again in early fall of 2010. Results indicated that over a three-month break from mandatory physical training, a significant decrease in VO2max was seen for both genders in ROTC cadets. PMID- 27182393 TI - Stability Ball Sitting Elevates Peak Arm Ergometry Oxygen Consumption and Heart Rate. AB - This study compared sitting on a stability ball (B) to sitting on a chair (C) during arm ergometry to determine the impact on peak VO2, peak heart rate (HR), and exercise intensity prescription. Open-circuit spirometer, blood pressure, and HR were monitored during rest and continuous graded exercise test to exhaustion using an arm ergometer. Twenty-seven apparently healthy adults exercised twice, once at B and the other trial C (order randomized), with 60 minutes of rest between trials. ANOVA for repeated measures (alpha < 0.05) and paired t testing using Holm's-sequential Bonferroni were used to analyze results for 30 W, 45 W, Penultimate, and Peak stages of exercise. VO2 was significantly higher (8% to 12%, P < 0.001) for all stages of exercise for B compared to C. HR was significantly higher (P < 0.001) only at the Penultimate and Peak levels (3% and 2%, respectively) for B compared to C; all other sub-maximal HRs were not significantly different. There were no significant main effects or interactions (P>= 0.138) when VO2 and HR were expressed as percentage of maximum. Compared to chair sitting, the stability ball has a greater absolute metabolic response with little impact on HR. Prescribing exercise with absolute MET levels should consider this; however, intensity as a percentage of maximum may not be affected by the stability ball. PMID- 27182394 TI - Correlation of Air Displacement Plethysmography with Alternative Body Fat Measurement Techniques in Men and Women. AB - Obesity has reached epidemic proportions with serious health consequences. Techniques used to measure body fat (BF) yield variable BF estimates, and this variability may lead to underestimation or overestimation of BF and subsequent treatment options. The measurements that are most accurate (Dual-Energy X-ray Absorptiometry (DEXA) and Air Displacement Plethysmography (ADP)) are expensive and often unavailable. The purpose of this study is to find the commonly available BF measurement that is the most accurate and practical for individual body types in the general population and compare these measurements to ADP (BOD POD(r)) as the standard. Field measurements include skinfolds (SKF), upper, lower, and whole body bioelectrical impedance (BI), waist and hip circumference ratios, body mass index calculations (BMI), and ADP. Our data indicate that BI is the least accurate measurement of body fat in males and females (paired t-tests of % body fat: BI vs. ADP, p0.05). However, preliminary data suggest female- specific SKF equations more accurately predict body fat in obese males than male specific SKF equations. Given the current obesity trends, it is imperative to update these formulae to accurately reflect the current population. PMID- 27182395 TI - The Evaluation of a Circumference-based Prediction Equation to Assess Body Composition Changes in Men. AB - This study evaluated the validity of the current U.S. Department of Defense (DOD) circumference-based prediction equation for males to detect body composition changes in comparison to air-displacement plethysmography (ADP). Body composition was assessed using ADP and the DOD equation at the beginning and end of an academic school year among 21 male (18-29 years-old) Army ROTC cadets. Body mass significantly increased (+1.8 Kg) after 9 months. Significant method by time interactions for percent body fat (percent body fat), fat mass (FM), and fat-free mass were found (p = 0.022, p = 0.023, p = 0.023, respectively) as body composition changes were not tracked equally by the two methods. Regression and Bland-Altman analyses indicated a lack of agreement between methods as the DOD equation underestimated percent body fat and FM changes in comparison to ADP. Results suggest the DOD equation for males cannot adequately detect body composition changes following a small body mass gain. PMID- 27182396 TI - Measurements of Heart Rate and Accelerometry to Determine the Physical Activity Level in Boys Playing Paintball. AB - Paintball is a popular recreational sport played by 3.655 million Americans and may be sufficient physical activity to promote health. Paintball has been played as an organized sport since the 1980's and is essentially a game of tag, except instead of touching an opponent by hand opponents are tagged by shooting them with a paintball that leaves a mark indicating who has been eliminated. A previous evaluation of paintball as physical activity had 13 subjects undergo a VO2max test to develop a heart rate (HR) /oxygen consumption relationship, and it was observed that heart rates during paintball were 68-73% of the measured maximal HR. The present study used accelerometry and HR monitors to evaluate the quantity and intensity of physical activity in boys playing paintball. Eleven boys (12.7 +/- 1.0 y, 51.5 +/- 11.3 kg, 161.8 +/- 10.1 cm) engaged in a VO2max test to develop a HR/oxygen consumption correlation. On a separate day the boys played 7 games of outdoor paintball while wearing a HR monitor and accelerometer. The boys played paintball for 11.5 +/- 6.2 minutes/game for a total of 80.6 +/- 10.0 minutes of game play. Average HR during paintball play was 129.6 +/- 6.6 beats/min, representing 39.9 +/- 12.9% VO2max. Based on accelerometry, the boys accumulated 63.2 +/- 15.6 minutes of moderate intensity activity and 2.6 +/- 2.8 minutes of vigorous activity during paintball. These data suggest that playing paintball may be considered as physical activity that is > 3 METs, and thus health promoting. PMID- 27182397 TI - Comparison of Academic and Behavioral Performance between Athletes and Non athletes. AB - The Toronto Charter for Physical Activity (2010) and several national physical activity plans advocate sports participation as an important part of population targeted physical activity for youth. Emerging research evidence also suggests that sports participation during adolescents is linked to significant positive correlations with academic and behavioral performance. The purpose of this study was to compare academic and behavioral performance between male and female public school athletes (Total N=11,139; 38% Female) and non-athletes (Total N=23,891; 52% Female) in a convenient, ethnicity diverse, sample (grades 7-12) from the state of Texas (USA). We examined the passing rates of individual athletes and non-athletes on standardized tests (Texas Assessment of Knowledge and Skills, TAKS) for math, language arts, reading, writing, science, and social studies. We also examined the percentage of athletes and non-athletes for being "at risk," for dropping out of school and for the total average number of disciplinary actions. Chi-Square statistical analyses comparing athletes to non-athletes showed that athletes scored significantly better (p<0.05) on all standardized tests compared to non-athletes (passing rate ranges ranged from 77.1% to 92.9% versus 27.7% to 66.5% respectively). Athletes were at lower risk for dropout compared to non-athletes (35.6% versus 49.24%; p<0.05), and they had fewer disciplinary actions (mean of 0.85 per athletes per year versus 1.23 for non athletes; ANOVA, p<0.05). Our results support the research findings of others that participation in school sports is positively correlated to better academic and behavioral performances for athletes compared to non-athletes. PMID- 27182398 TI - The Effects of Proprioceptive Neuromuscular Facilitation Stretching on Post Exercise Delayed Onset Muscle Soreness in Young Adults. AB - Until recently, the scientific community believed that post-exercise stretching could reduce delayed onset muscle soreness (DOMS), but recent reviews of studies on the topic have concluded that pre- or post-exercise static stretching has no effect on mitigating DOMS. However, the effect of proprioceptive neuromuscular facilitation (PNF) post-exercise stretching on preventing DOMS has not been adequately studied. The purpose of this study was to determine the effect of post exercise PNF stretching on DOMS. Young adult participants (N=57) were randomly assigned to a PNF stretching group (n=19), a static stretching group (n=20), and to a no-stretching control group (n=18). All participants completed exercise designed to induce DOMS prior to post-exercise experimental stretching protocols. Participants rated their soreness level on a pain scale 24 and 48 hours post exercise. A 3 * 2 mixed ANOVA showed there was an effect for time (p<.01). Post hoc testing revealed that DOMS pain significantly decreased (p<.05) from 24 to 48 hours post-exercise for the PNF and control groups, but not for the static stretching group. Other analyses revealed a significant correlation (r=.61, p<.01) between the pre- and post-exercise stretch scores and the 48 hour post exercise pain score for the PNF group. Consistent with the results of previous research on post-exercise static stretching, these results indicate that post exercise PNF stretching also does not prevent DOMS. However, the correlation analysis suggests it is possible the pre-stretch muscle contractions of the post exercise PNF protocol may have placed a load on an already damaged muscle causing more DOMS for some participants. PMID- 27182399 TI - Wii, Kinect, and Move. Heart Rate, Oxygen Consumption, Energy Expenditure, and Ventilation due to Different Physically Active Video Game Systems in College Students. AB - Nintendo Wii, Sony Playstation Move, and Microsoft XBOX Kinect are home video gaming systems that involve player movement to control on-screen game play. Numerous investigations have demonstrated that playing Wii is moderate physical activity at best, but Move and Kinect have not been as thoroughly investigated. The purpose of this study was to compare heart rate, oxygen consumption, and ventilation while playing the games Wii Boxing, Kinect Boxing, and Move Gladiatorial Combat. Heart rate, oxygen consumption, and ventilation were measured at rest and during a graded exercise test in 10 males and 9 females (19.8 +/- 0.33 y, 175.4 +/- 2.0 cm, 80.2 +/- 7.7 kg,). On another day, in a randomized order, the participants played Wii Boxing, Kinect Boxing, and Move Gladiatorial Combat while heart rate, ventilation, and oxygen consumption were measured. There were no differences in heart rate (116.0 +/- 18.3 vs. 119.3 +/- 17.6 vs. 120.1 +/- 17.6 beats/min), oxygen consumption (9.2 +/- 3.0 vs. 10.6 +/- 2.4 vs. 9.6 +/- 2.4 ml/kg/min), or minute ventilation (18.9 +/- 5.7 vs. 20.8 +/- 8.0 vs. 19.7 +/- 6.4 L/min) when playing Wii boxing, Kinect boxing, or Move Gladiatorial Combat (respectively). Playing Nintendo Wii Boxing, XBOX Kinect Boxing, and Sony PlayStation Move Gladiatorial Combat all increase heart rate, oxygen consumption, and ventilation above resting levels but there were no significant differences between gaming systems. Overall, playing a "physically active" home video game system does not meet the minimal threshold for moderate intensity physical activity, regardless of gaming system. PMID- 27182400 TI - Determination of Anaerobic Threshold by Heart Rate or Heart Rate Variability using Discontinuous Cycle Ergometry. AB - The purpose was to determine if heart rate (HR) and heart rate variability (HRV) responses would reflect anaerobic threshold (AT) using a discontinuous, incremental, cycle test. AT was determined by ventilatory threshold (VT). Cyclists (30.6+/-5.9y; 7 males, 8 females) completed a discontinuous cycle test consisting of 7 stages (6 min each with 3 min of rest between). Three stages were performed at power outputs (W) below those corresponding to a previously established AT, one at W corresponding to AT, and 3 at W above those corresponding to AT. The W at the intersection of the trend lines was considered each metric's "threshold". The averaged stage data for Ve, HR, and time- and frequency-domain HRV metrics were plotted versus W. The W at the "threshold" for the metrics of interest were compared using correlation analysis and paired sample t-test. In all, several heart rate-related parameters accurately reflected AT with significant correlations (p<=0.05) were observed between AT W and HR, mean RR interval (MRR), low and high frequency spectral energy (LF and HR, respectively), high frequency peak (fHF), and HFxfHF metrics' threshold W (i.e., MRRTW, etc.). Differences in HR or HRV metric threshold W and AT for all subjects were less than 14 W. The steady state data from discontinuous protocols may allow for a true indication of steady-state physiologic stress responses and corresponding W at AT, compared to continuous protocols using 1-2 min exercise stages. PMID- 27182401 TI - Self-determined Engagement in Physical Activity and Sedentary Behaviors of US College Students. AB - Although the importance of promoting physical activity is well established, researchers have recently considered "sedentary behaviors" as another key risk factor for chronic disease. However, little is known about the motivational processes regulating sedentary behavior on a daily basis. A substantial amount of research has been based on the self-determination theory to examine the motivational processes regulating physical activity behaviors. However, only limited attention has been paid to sedentary behaviors from this theoretical perspective. This study aims to identify and understand motivational aspects related to sedentary behavior from a self-determination perspective. A convenience sample of undergraduate students (N=875) enrolled in a university required Lifetime Physical Activity and Fitness class completed an online survey which inquired about physical activity and sedentary behaviors as well as about motivational variables related to these behaviors. Physical activity variables were inversely and only slightly related to sedentary behavior (rho = -.084 to .146, p < .05). Psychological needs and behavioral regulations together explained 14.3% of the variance in moderate-to-vigorous physical-activity (p < .001), but only 2.8% of the variance in sedentary behavior (p = .002). These findings suggest physical activity and sedentary behaviors are explained by unique motivational factors. PMID- 27182402 TI - Cardiovascular and Metabolic Demads of the Kettlebell Swing using Tabata Interval versus a Traditional Resistance Protocol. AB - : Tabata (TAB) training, consisting of eight cycles of 20 seconds of maximal exercise followed by 10 seconds of rest, is time-efficient, with aerobic and anaerobic benefit. This study investigated the cardiovascular and metabolic demands of a TAB versus traditional (TRAD) resistance protocol with the kettlebell swing. Fourteen young (18-25y), non-obese (BMI 25.7+/-0.8 kg/m2) participants reported on three occasions. All testing incorporated measurements of HR, oxygen consumption, and blood lactate accumulation. Each participant completed Tabata kettlebell swings (male- 8kg, female- 4.5kg; 8 intervals; 20s maximal repetitions, 10s rest). On a subsequent visit (TRAD), the total swings from the TAB protocol were evenly divided into 4 sets, with 90s rest between sets. Outcome measures were compared using paired t-tests. The TAB was completed more quickly than the TRAD protocol (240.0+/-0.0 v. 521.5+/-3.3 sec, P<0.01), at a higher perceived exertion (Borg RPE; 15.1+/-0.7 v. 11.7+/-0.9, P<0.01). The TAB elicited a higher average VO2 value (33.1+/-1.5 v. 27.2+/-1.6 ml/kg/min, P<0.01), percent of VO2peak achieved (71.0+/-0.3 v. 58.4+/-0.3%, P<0.01), maximal HR (162.4+/-4.6 v. 145.6+/-4.8 bpm, P<0.01), and post-exercise blood lactate concentration (6.4+/-1.1 v. 3.7+/-0.5 mmol/L, P<0.01). CONCLUSION: The kettlebell swing demonstrated significantly greater cardiovascular and metabolic responses within a TAB vs. TRAD framework. Appropriate screening and risk stratification are advised before implementing kettlebell swings. PMID- 27182403 TI - The Physiologic and Behavioral Implications of Playing Active and Sedentary Video Games in a Seated and Standing Position. AB - Previous studies have assessed physiologic response while playing video games per manufacturer instructions with participants standing during active video game play and seated during sedentary game play. It is not known whether an assigned seated or standing position affects positional preference and oxygen consumption (VO2) while gaming. The purpose of the study was to assess VO2 and preference of playing active and sedentary video games in a seated and standing position. VO2 was assessed in 25 participants during four, 20-minute conditions; resting, PlayStation 2 Madden NFL Football 2011, Nintendo Wii-Sports Boxing and Nintendo Wii Madden NFL Football 2011. Each condition was divided into two positional conditions (10 minutes seated, 10 minutes standing) and each participant indicated their positional preference after each 20-minute condition. Standing VO2 (4.4 +/- 0.2 ml * kg-1 * min-1 PS2, 4.6 +/- 0.1 ml * kg-1 * min-1 Wii Madden, 6.8 +/- 0.3 ml * kg-1 * min-1Wii Boxing) was significantly (p <= 0.001) greater than seated VO2 (4.0 +/- 0.1 ml * kg-1 * min-1 PS2, 4.2 +/- 0.1 ml * kg-1 * min-1 Wii Madden, 6.1 +/- 0.3 ml * kg-1 * min-1Wii Boxing) for each gaming condition. Participants preferred (p <= 0.001) to sit for all gaming conditions except Wii Boxing. Playing video games while standing increases VO2 to a greater extent than playing the same games in a seated position. Standing was only preferred for the most physiologically challenging game, Wii Boxing. Gaming position should be considered when assessing the physiologic and behavioral outcomes of playing video games. PMID- 27182404 TI - An Acute Bout of Self-Myofascial Release in the Form of Foam Rolling Improves Performance Testing. AB - Recent developments in the strength and conditioning field have shown the incorporation of foam rolling self-myofascial release in adjunct with a dynamic warm-up. This is thought to improve overall training performance; however, minimal research exists supporting this theory. Therefore, determining if an acute bout of foam rolling self-myofascial release in addition to a dynamic warm up could influence performance is of importance. In order to do so, eleven athletically trained male subjects participated in a two condition, counterbalanced, crossover within-subjects study comparing two particular warm-up routines. The two warm-up routines compared were a total-body dynamic warm-up (DYN) and a total-body dynamic warm-up in adjunct with a self-myofascial release, total-body foam rolling session (SMR). Following each warm-up condition, subjects performed tests of flexibility, power, agility, strength, and speed. Paired samples T-tests were utilized to determine if there were any significant differences in test results between conditions (DYN vs. SMR). The data indicated that SMR was effective at improving power, agility, strength, and speed when compared to DYN (P <= 0.024). A warm-up routine consisting of both a dynamic warm up and a self-myofascial release, total-body foam rolling session resulted in overall improvements in athletic performance testing. PMID- 27182405 TI - Acute Post-Activation Potentiation Effects in NCAA Division II Female Athletes. AB - Post-activation potentiation (PAP) is a phenomenon in which the power output of a muscle is immediately enhanced after heavy resistance exercise. Whereas the majority of PAP research has examined males, minimal research exists as to how female athletes respond. Therefore, the purpose of this study was to investigate the acute PAP response of back squats on static squat jump (SSJ) performance among NCAA Division II female athletes. Female athletes (n=29) who were current roster members from basketball, softball, and volleyball, performed 3 SSJ prior to 3 repetitions of the back squat exercise at 90% 1RM. After a 5-min rest, athletes once again performed 3 SSJ for maximal height, with peak power calculated using the Sayers equation. There was a significant interaction effect observed between time and team, p=0.022; post-hoc tests indicated that the volleyball team had a significant decrease in power, p=0.008. The main effect for time was not significant, p=0.279, indicating for the group as a whole, there was no evidence of a PAP response. The main effect for team was also non-significant, p=0.173, indicating no difference in power outputs by team. Strength and conditioning coaches who work with female athletes should be aware that the successful implementation of PAP complexes within this population appears to be highly individualized. Therefore, the use of PAP complexes in female athletes should consider both the absolute and relative strength of each athlete in conjunction with the length of the rest period when attempting to optimize the PAP response. PMID- 27182406 TI - The Influence of Exercise Environment and Gender on Mood and Exertion. AB - This study examined the influence of exercise environment and gender on post exercise mood and exertion. College student participants (55 females, 49 males) were instructed to pedal a stationary bike at a moderate pace for 20 minutes. Participants were randomly assigned to one of three laboratory conditions: (1) exercising in front of a mirror and posters showing ideal fit body types (i.e., celebrity male and female personal trainers), (2) exercising in front of a mirror only, or (3) a control condition in which participants exercised without a mirror or posters. The Activation-Deactivation Adjective Check List (AD-ACL), measuring exercise-induced mood states, was administered both before and after exercise. Average bike speed throughout the exercise session measured exertion. Mirrors and posters of ideally fit celebrities did interact with gender on post-exercise tension in that women felt most tense after exercising in front of the mirror and posters while men were most tense after exercising in front of the mirror only. Exercise exertion was also impacted by experimental condition such that participants rode significantly faster in the mirror and posters condition. There was no significant interaction of gender and condition on exercise exertion, but women pedaled fastest in the mirror and poster condition relative to the other conditions. Results suggest that exercise exertion and tension reduction are partially a by-product of gender and exercise environment. PMID- 27182407 TI - Occupational Sitting and Physical Activity Among University Employees. AB - The prevalence of overweight and obese in the U.S. has been thoroughly documented. With the advent of inactivity physiology research and the subsequent interest in sedentary behavior, the work environment has come under closer scrutiny as a potential opportunity to reverse inactivity. Therefore, the purpose of this study was to determine the sitting and physical activity (PA) habits among different classifications of university employees. University employees (n=625) completed an online survey based on the Occupational Sitting and Physical Activity Questionnaire (OSPAQ). Participants were instructed to describe time spent sitting, standing, walking, and in heavy physical labor during the last seven days, along with the number of breaks from sitting taken per hour. To establish habitual patterns of PA outside of work, employees recalled their participation in structured PA in the past seven days. Prior to data analysis, employees were categorized as Administration, Faculty, Staff, or Facilities Management. Statistically significant differences were found among employee classifications for min sit/d, p<.001; min stand/d, p<.001; min walk/d, p<.001; and min heavy labor/d, p<.001. No significant differences were found for breaks/h from sitting, p=.259 or participation in structured PA, p=. 33. With the exception of facilities management workers, university employees spent 75% of their workday seated. In conjunction with low levels of leisure time PA, university employees appear to be prime candidates for workplace interventions to reduce physical inactivity. PMID- 27182408 TI - Muscle Activity in Single- vs. Double-Leg Squats. AB - Muscular activity, vertical displacement and ground reaction forces of back squats (BS), rear-leg elevated split squats (RLESS) and split squats (SS) were examined. Nine resistance-trained men reported for two sessions. The first session consisted of the consent process, practice, and BS 1-repetition maximum testing. In the second session, participants performed the three exercises while EMG, displacment and ground reaction force data (one leg on plate) were collected. EMG data were collected from the gluteus maximus (GMX), biceps femoris (BF), semitendinosus (ST), rectus femoris (RF), vastus lateralis (VL), vastus medialis (VM), tibialis anterior (TA), and medial gastrocnemius (MGas) of the left leg (non-dominant, front leg for unilateral squats). Load for BS was 85% one repetition maximum, and RLESS and SS were performed at 50% of BS load. Repeated measures ANOVA was used to compare all variables for the three exercises, with Bonferroni adjustments for post hoc multiple comparisons, in addition to calculation of standardized mean differences (ES). Muscle activity was similar between exercises except for biceps femoris, which was significantly higher during RLESS than SS during both concentric and eccentric phases (ES = 2.11; p=0.012 and ES= 2.19; p=0.008), and significantly higher during BS than the SS during the concentric phase (ES = 1.78; p=0.029). Vertical displacement was similar between all exercises. Peak vertical force was similar between BS and RLESS and significantly greater during RLESS than SS (ES = 3.03; p=0.001). These findings may be helpful in designing resistance training programs by using RLESS if greater biceps femoris activity is desired. PMID- 27182409 TI - VO2 Reserve vs. Heart Rate Reserve During Moderate Intensity Treadmill Exercise. AB - VO2 and heart rate (HR) are widely used when determining appropriate training intensities for clinical, healthy, and athletic populations. It has been shown that if the % reserve (%R) is used, rather than % of max, HR and VO2 can be used interchangeably to accurately prescribe exercise intensities. Thus, heart rate reserve (HRR) can be prescribed if VO2 reserve (VO2R) is known. Therefore, the purpose of this study was to compare VO2 R and HRR during moderate intensity exercise (50%R). Physically active college students performed a maximal treadmill test to exhaustion. During which VO2 and HR were monitored to determine max values. Upon completion of the maximal test, calculations were made to determine the % grade expected to yield approximately 50% of the subjects VO2R. Subjects then returned to complete the submaximal test (50%R) at least two days later. The %VO2R and %HRR were calculated and compared to the predicted value as well as to each other. Statistical analysis revealed that VO2 at 50%R was significantly greater than the actual VO2 achieved, p < .001. Conversely, the mean predicted HR at 50%R was significantly less than the actual HR achieved, p < .001. In conclusion, this study indicated that VO2 could be more accurately predicted than HR during moderate intensity exercise. The weak correlation between VO2R and HRR indicates that caution should be used when relying on a HR to determine VO2. PMID- 27182410 TI - Actual Versus Predicted Cardiovascular Demands in Submaximal Cycle Ergometer Testing. AB - The Astrand-Rhyming cycle ergometer test (ARCET) is a commonly administered submaximal test for estimating aerobic capacity. Whereas typically utilized in clinical populations, the validity of the ARCET to predict VO2max in a non clinical population, especially female, is less clear. Therefore, the purpose of this study was to determine the accuracy of the ARCET in a sample of healthy and physically active college students. Subjects (13 females, 10 males) performed a maximal cycle ergometer test to volitional exhaustion to determine VO2max. At least 48 hours later, subjects performed the ARCET protocol. Predicted VO2max was calculated following the ARCET format using the age corrected factor. There was no significant difference (p=.045) between actual (41.0+/-7.97 ml/kg/min) and predicted VO2max (40.3+/-7.58 ml/kg/min). When split for gender there was a significant difference between actual and predicted VO2 for males, (45.1+/-7.74 vs. 42.7+/-8.26 ml/kg/min, p=0.029) but no significant difference observed for females, (37.9+/-6.9 vs. 38.5+/-6.77 ml/kg/min, p=0.675). The correlation between actual and predicted VO2 was r=0.84, p<0.001 with an SEE= 4.3 ml/kg/min. When split for gender, the correlation for males was r=0.94, p<0.001, SEE=2.72 ml/kg/min; for females, r=0.74, p=0.004, SEE=4.67 ml/kg/min. The results of this study indicate that the ARCET accurately estimated VO2max in a healthy college population of both male and female subjects. Implications of this study suggest the ARCET can be used to assess aerobic capacity in both fitness and clinical settings where measurement via open-circuit spirometry is either unavailable or impractical. PMID- 27182411 TI - Use of Sports Science Knowledge by Turkish Coaches. AB - The purpose of this study is to examine the following research questions in Turkish coaching context: a) What are coaches' perceptions on the application of sport science research to their coaching methods? b) What sources do coaches utilize to obtain the knowledge they need? c) What barriers do coaches encounter when trying to access and apply the knowledge they need for their sport? In addition, differences in research questions responses were examined based on gender, years of coaching experience, academic educational level, coaching certificate level, coaching team or individual sports, and being paid or unpaid for coaching. The participants were 321 coaches (255 men, 66 women) from diverse sports and coaching levels working in Ankara. The questionnaire "New Ideas for Coaches" by Reade, Rodgers and Hall (2008) was translated, adapted into Turkish, and validated for the current study. According to our findings among Turkish coaches, there is a high prevalence of beliefs that sport science contributes to sport (79.8%);however, there are gaps between what coaches are looking for and the research that is being conducted. Coaches are most likely to attend seminars or consult other coaches to get new information. Scientific publications were ranked very low by the coaches in getting current information. The barriers to coaches' access to sport science research are finding out the sources of information, being able to implement the sport science knowledge into the field of coaching, lack of monetary support in acquiring knowledge, and language barriers. Also, differences in perceptions and preferences for obtaining new information were identified based on coaches' gender, coaching contexts (i.e., professional-amateur), coaching settings (i.e., team/individual), and their other demographic characteristics (i.e., coaching experience, coaching educational level, and coaching certificate level). Future coach education programs should emphasize the development of coaches' competencies in identifying and accessing eligible sports science knowledge sources and lack of money for acquiring information while also tailoring the messages based on differences in coaching contexts, coaching settings, and coaches' demographic characteristics so as to ensure successful knowledge transfer. PMID- 27182412 TI - The Effects of a 12-Week Faculty and Staff Exercise Program on Health-Related Variables in a University Setting. AB - The obesity epidemic has grown in the past decade due to physical inactivity (i.e., having a sedentary job) and an increase in caloric intake. This problem combined with the reluctance of many faculty and staff members exercising in the same environment as student's presents a unique challenge in an academic setting. The purpose of this study was to examine the effectiveness of a 12-week exercise program focused toward the faculty and staff in improving several health-related variables such as curl-ups, push-ups, sit-and-reach, and balance. Fifty-seven faculty and staff participated in the current study. Participants engaged in a variety of exercise classes taught by certified instructors three days a week for 12-weeks. Paired samples t-tests illustrated a significant (p < 0.001) decrease in body mass and significant (p <= 0.001) improvements in curl-ups, push-ups, sit and-reach, and balance. This data demonstrates that a 12-week faculty and staff exercise program has the potential to improve performance in several health related variables such as curl-ups, push-ups, sit-and-reach, and balance. The ability of this program to improve health-related variables and possibly delay or prevent the development of overweight and/or obesity, sarcopenia, and other chronic diseases is encouraging. PMID- 27182413 TI - The Effects of Vascular Occlusion Training on Respiratory Exchange Ratio and Energy Expenditure When Coupled With Cardiovascular Training. AB - Vascular occlusion training is a novel training modality that has received considerable attention in the exercise science literature. The current study is the first of its kind to look at the effects of vascular occlusion training on substrate utilization when combined with aerobic training. This study examined the effects of pairing a vascular occlusion training protocol with a bout of submaximal aerobic exercise on energy expenditure (EE) and fuel use during exercise. Subjects performed a 20 minute bout of sub-maximal aerobic exercise either exclusively, or after performing a body weight squat protocol either with or without vascular occlusion. Peak lactate concentrations, EE and respiratory exchange ratio (RER) were all measured. A repeated measures analysis of variance was performed to look at differences among groups and interactions among protocols. The results suggest no difference in peak lactate (7.29 mmol/dl vs. 10.17 mmol/dl; F=0.946; p>0.05) or EE (92.09 Kcals vs 93.48 Kcals; F=0.898 p>0.05) among protocols. However, there does appear to be a shift in substrate utilization towards fatty acid oxidation by performing either a vascular occlusion training protocol (mean RER= 0.836) or a protocol of body weight squats (mean RER= 0.823) prior to aerobic training in comparison to performing aerobic training alone (mean RER= 0.881). There were, however, no significant differences between the occlusion protocol and the body weight squat protocol prior to the aerobic training. These results suggest that while there are no differences in overall caloric expenditure between protocols, performing either a resistance training protocol or a vascular occlusion training protocol shifts substrate utilization in favor of fatty acid oxidation over the oxidation of carbohydrates. PMID- 27182414 TI - Reflective Blankets Do Not Effect Cooling Rates after Running in Hot, Humid Conditions. AB - Reflective blankets (RB) are often provided at the conclusion of endurance events, even in extreme environments. The implications could be dangerous if increased core body temperature (CBT) is exacerbated by RB. To evaluate the effect of RB on cooling rate for individuals walking or sitting after intense running. Pilot, randomized control trial experimental design. Environmental chamber. Recreational runners (age=25+/-5y; mass=76.8+/-16.7kg; height=177+/-9cm) completed an 8km (actual mean distance=7.5+/-1.1km). We randomly assigned participants into one of four groups: walking with blanket (WB=5), walking without blanket (WNB=5), sitting with blanket (SB=5), or sitting without blanket (SNB=4). Participants ran on a treadmill at their own pace until volitional exhaustion, achieving the 8km distance, or experiencing CBT=40 degrees C. Every three minutes during the running (time determined by pace) and cooling protocol (62 min in chamber), we measured CBT, HR, and Borg scale, and environmental conditions. We evaluated cooling rate, peak physiological variables, pace, and environment by condition using a Kruskal-Wallis non-parametric one-way ANOVAs. We identified similar exercise sessions (df=3; CBT chi2=0.921, p=0.82; HR chi2=7.446, p=0.06; Borg chi2= 5.732, p=0.13; pace chi2=0.747, p=0.86) and similar environmental characteristics between conditions (df=3; Wet Bulb Globe Temperature=26.18+/-2.78 degrees C, chi2=1.552, p=0.67). No significant differences between conditions on cooling rate (df=3, chi2=2.301, p=0.512) were found, suggesting RBs neither cool nor heat the body, whether seated (SB=0.021+/ 0.011deg/min; SNB=0.029+/-0.002deg/min) or walking (WB=0.015+/-0.025deg/min; WNB=0.021+/-0.011deg/min) in a hot, humid environment. CBT in distance runners is not altered by the use of a RB during a seated or walking cool down after a strenuous run. PMID- 27182415 TI - TRX Suspension Training: A New Functional Training Approach for Older Adults - Development, Training Control and Feasibility. AB - Because of its proximity to daily activities functional training becomes more important for older adults. Sling training, a form of functional training, was primarily developed for therapy and rehabilitation. Due to its effects (core muscle activation, strength and balance improvements), sling training may be relevant for older adults. However, to our knowledge no recent sling training program for healthy older adults included a detailed training control which is indeed an essential component in designing and implementing this type of training to reach positive effects. The purpose of this study was to develop a TRX Suspension Training for healthy older adults (TRX-OldAge) and to evaluate its feasibility. Eleven participants finished the 12 week intervention study. All participants trained in the TRX-OldAge whole-body workout which consists of seven exercises including 3-4 progressively advancing stages of difficulty for every exercise. At each stage, intensity could be increased through changes in position. Feasibility data was evaluated in terms of training compliance and a self-developed questionnaire for rating TRX-OldAge. The training compliance was 85 %. After study period, 91 % of the participants were motivated to continue with the program. The training intensity, duration and frequency were rated as optimal. All participants noted positive effects whereas strength gains were the most. On the basis of the detailed information about training control, TRX-OldAge can be individually adapted for each older adult appropriate to its precondition, demands and preference. PMID- 27182416 TI - The Relationship of Gender and Self-Efficacy on Social Physique Anxiety among College Students. AB - The anxiety or fear associated with physique evaluation is defined as Social Physique Anxiety (SPA). Numerous studies have examined this construct, yet a gap exists exploring this phenomenon among current college students with SPA, self efficacy, and gender concurrently. Therefore, the purposes of this study included quantitatively analyzing the association between SPA, gender, and self-efficacy. Participants included 237 students at a Southeastern university participating in jogging, body conditioning, or weight training courses. Analysis of Variance yielded a significant main effect for self-efficacy as well, as those with lower self-efficacy displayed higher levels of SPA (p< 0.001). Stepwise regression analysis indicated self-efficacy and gender were both significant predictors of SPA. This information could aid in creating interventions designed to decrease the prevalence of SPA and increase levels of self-efficacy among the current college student population. PMID- 27182417 TI - Effect of Beetroot Juice on Moderate-Intensity Exercise at a Constant Rating of Perceived Exertion. AB - Dietary nitrate supplementation has been shown to reduce oxygen consumption at a fixed work rate. We questioned whether a similar effect would be observed during variable work rate exercise at a specific rating of perceived exertion (RPE), as is commonly prescribed for aerobic training sessions. Using a double-blind, placebo controlled, crossover design, ten females (25 +/- 3 years; VO2peak 37.1 +/- 5.3 ml/kg/min) performed two 20-min cycle ergometer trials at a constant RPE of 13 (somewhat hard) 2.5 hours following ingestion of 140 ml of concentrated beetroot juice (12.9 mmol nitrate), or nitrate-depleted placebo. Performance was measured in terms of total VO2 (L) consumed and total mechanical work (kJ) accomplished across each trial. Following each experimental trial, subjects rode at 75W for an additional 5 min to determine the effect of beetroot juice on fixed work rate exercise. Coefficients of variation in total VO2 (L) and work performed (kJ) during the RPE 13 clamp trials were 8.2 and 9.5%, respectively. Consumption of beetroot juice did not affect total VO2 or work performed during RPE 13 exercise, but lowered resting systolic blood pressure by ~5 mmHg (P=0.041) and oxygen consumption at 75W by ~4% (P=0.048), relative to placebo. Since the effect of beetroot juice on oxygen consumption is small and may be masked by daily variability during self-regulated exercise, it is unlikely to have a notable effect on daily training. PMID- 27182418 TI - Use and Misuse of the Likert Item Responses and Other Ordinal Measures. AB - Likert, Likert-type, and ordinal-scale responses are very popular psychometric item scoring schemes for attempting to quantify people's opinions, interests, or perceived efficacy of an intervention and are used extensively in Physical Education and Exercise Science research. However, these numbered measures are generally considered ordinal and violate some statistical assumptions needed to evaluate them as normally distributed, parametric data. This is an issue because parametric statistics are generally perceived as being more statistically powerful than non-parametric statistics. To avoid possible misinterpretation, care must be taken in analyzing these types of data. The use of visual analog scales may be equally efficacious and provide somewhat better data for analysis with parametric statistics. PMID- 27182419 TI - Validation of Maximal Heart Rate Prediction Equations Based on Sex and Physical Activity Status. AB - The purpose of the study was to determine if measured maximal heart rate (HRmax) was affected by sex or aerobic training status, and to determine the accuracy of three common clinical age-prediction maximal heart rate regression equations used to predict HRmax: HRmax= 220 - age, HRmax= 226 - age, and HRmax= 208 - (0.7 . age). Fifty-two participants in total, 30 of which were in the active group (15 M, 15 F) and 22 subjects in the sedentary group (9 M, 13 F), within the age range of 18-25 years and with a normal BMI (18.5-24.9 kg.m-2) underwent a Bruce maximal treadmill exercise protocol. The effect of sex and training status on HRmax was analyzed through a two-way ANOVA, and the effect of sex, aerobic training status, and regression equation on accuracy of the HRmax prediction was assessed with a three-way ANOVA (alpha=0.05). Overall, males had a higher HRmax than females (198.3 v. 190.4 beats * min-1, p<.001) and sedentary individuals had higher measured HRmax than active individuals (197.3 v. 191.4 beats * min-1, p=.002). Furthermore, HRmax= 208 - (0.7 . age)(equation 3) calculated the smallest signed and unsigned residuals from the difference between observed HRmax and predicted HRmax values for the significant main effects of equation (3), equation * sex (females * 3), and equation * activity level (active * 3). Therefore, based on our results, we conclude that HRmax= 208 - (0.7 . age) has greater accuracy than the other two equations studied for predicting observed values of HRmax in 18-25 year olds. PMID- 27182420 TI - Comparison of Affect and Cardiorespiratory Training Responses Between Structured Gym Activities and Traditional Aerobic Exercise in Children. AB - Physical activities (PA) that are pleasurable are likely to be repeated. Structured gym activities (SGA) are defined as dodging, chasing, and fleeing games. Traditional aerobic exercises (TAE) are defined as treadmill, cycle ergometer, and elliptical exercise. The purpose of this investigation was to compare affect and cardiorespiratory training responses between SGA and TAE in children. Thirty-two participants (9.3+/-0.2) were randomized to either the SGA or TAE group. Exercise training was seven weeks, with two sessions per week, for 35 minutes per session. Affect was measured by the (+5 (pleasurable) to -5 (displeasurable)) feelings scale. Affect was recorded at the mid-point and end of each exercise session. The 20-meter pacer test was used to assess cardiorespiratory fitness at baseline and post intervention. Affect responses and heart rates were averaged across all exercise sessions. The SGA group scored 2.77+/-0.2 affect units higher than the TAE group (p < 0.0001). The TAE group significantly increased cardiorespiratory fitness (baseline 47.8+/-3.8; post 49.1+/-3.1 ml.kg-1.min-1; p = 0.023) with no change in the SGA group (baseline 46.3+/-3.5; post 47.2+/-2.7 ml.kg-1.min-1; p = 0.127). SGA reported more positive affect, suggesting they experienced greater pleasure during the exercise sessions than the TAE participants. SGA activities promote more positive affect, and therefore may increase children's PA participation. PMID- 27182421 TI - The Effect of CardioWaves Interval Training on Resting Blood Pressure, Resting Heart Rate, and Mind-Body Wellness. AB - An experimental study to examine the effects of CardioWaves interval training (CWIT) and continuous training (CT) on resting blood pressure, resting heart rate, and mind-body wellness. Fifty-two normotensive (blood pressure <120/80 mmHg), pre-hypertensive (120-139/80-89 mmHg), and hypertensive (>140/90 mmHg) participants were randomly assigned and equally divided between the CWIT and CT groups. Both groups participated in the assigned exercise protocol 30 minutes per day, four days per week for eight weeks. Resting blood pressure, resting heart rate, and mind-body wellness were measured pre- and post-intervention. A total of 47 participants (15 females and 32 males) were included in the analysis. The CWIT group had a non-significant trend of reduced systolic blood pressure (SBP) and increased diastolic blood pressure (DBP) while the CT group had a statistically significant decrease in awake SBP (p = 0.01) and total SBP (p = 0.01) and a non significant decrease in DBP. With both groups combined, the female participants had a statistically significant decrease in awake SBP (p = 0.002), asleep SBP (p = 0.01), total SBP (p = 0.003), awake DBP (p = 0.02), and total DBP (p = 0.05). The male participants had an increase in SBP and DBP with total DBP showing a statistically significant increase (p = 0.05). Neither group had a consistent change in resting heart rate. Both groups showed improved mind-body wellness. CWIT and CT reduced resting blood pressure, with CT having a greater effect. Resting heart rate did not change in either group. Additionally, both CWIT and CT improved mind-body wellness. PMID- 27182422 TI - Increasing Lean Mass and Strength: A Comparison of High Frequency Strength Training to Lower Frequency Strength Training. AB - The purpose of this study was to determine the effect strength training frequency has on improvements in lean mass and strength. Participants were 7 women and 12 men, age (chi= 34.64 years +/- 6.91 years), with strength training experience, training age (chi= 51.16 months +/- 39.02 months). Participants were assigned to one of two groups to equal baseline group demographics. High frequency training group (HFT) trained each muscle group as the agonist, 3 times per week, exercising with 3 sets per muscle group per session (3 total body workouts). Low frequency training group (LFT) trained each muscle group as the agonist one time per week, completing all 9 sets during that one workout. LFT consisted of a routine split over three days: 1) pectoralis, deltoids, and triceps; 2) upper back and biceps; 3) quadriceps, hamstrings, calves, and abdominals. Following eight weeks of training, HFT increased lean mass by 1.06 kg +/- 1.78 kg, (1.9%), and LFT increased lean mass by .99 kg +/- 1.31 kg, (2.0%). HFT strength improvements on the chest press was 9.07 kg +/- 6.33 kg, (11%), and hack squat 20.16 kg +/- 11.59 kg, (21%). LFT strength improvements on chest press was 5.80kg +/- 4.26 kg, (7.0%), and hack squat 21.83 kg +/- 11.17 kg, (24 %). No mean differences between groups were significant. These results suggest that HFT and LFT of equal set totals result in similar improvements in lean mass and strength, following 8 weeks of strength training. PMID- 27182423 TI - Metabolic and Energy Cost of Sitting, Standing, and a Novel Sitting/Stepping Protocol in Recreationally Active College Students. AB - The purpose of this study was to compare the differences in metabolic and energy cost (MEC) of college students while seated, standing, and during a sitting/stepping protocol. Participants were assessed via indirect calorimetry for 20 min in each of the following conditions: 1) seated in a standard office chair, 2) standing in place, and 3) a sitting/stepping protocol in which participants performed 1 min of stepping in place at 90 bpm, sat for 9 min, then repeated the stepping and sitting sequence once more. Participants completed each of the 3 trials in the aforementioned order, preceded with a 3 min acclimation period in each condition. A significant difference in MEC was observed between the 3 conditions, p < 0.001. Pairwise comparisons indicated that the sitting/stepping protocol resulted in significantly greater MEC than the seated and standing conditions (p < 0.001). Additionally, the standing protocol resulted in significantly greater MEC than the seated protocol (p < 0.001). The significant differences and large effect sizes between conditions indicate that interspersing sedentary bouts with brief activity can substantially increase MEC. Broader application of these findings may provide health promotion professionals with novel strategies to reduce sedentary behavior and improve health. PMID- 27182425 TI - Convergence in Healthcare: Providers, Employers, and Health Plans. PMID- 27182424 TI - The Effect of Training Intensity on VO2max in Young Healthy Adults: A Meta Regression and Meta-Analysis. AB - Exercise training at a variety of intensities increases maximal oxygen uptake (VO2max), the strongest predictor of cardiovascular and all-cause mortality. The purpose of the present study was to perform a systematic review, meta-regression and meta-analysis of available literature to determine if a dose-response relationship exists between exercise intensity and training-induced increases in VO2max in young healthy adults. Twenty-eight studies involving human participants (Mean age: 23+/-1 yr; Mean VO2max: 3.4+/-0.8 l.min-1) were included in the meta regression with exercise training intensity, session dose, baseline VO2max, and total training volume used as covariates. These studies were also divided into 3 tertiles based on intensity (tertile 1: ~60-70%; 2: ~80-92.5%; 3: ~100 250%VO2max), for comparison using separate meta-analyses. The fixed and random effects meta-regression models examining training intensity, session dose, baseline VO2max and total training volume was non-significant (Q4=1.36; p=0.85; R2=0.05). There was no significant difference between tertiles in mean change in VO2max (tertile 1:+0.29+/-0.15 l/min, ES (effect size) =0.77; 2:+0.26+/-0.10 l/min, ES=0.68; 3:+0.35+/-0.17 l/min, ES=0.80), despite significant (p<0.05) reductions in session dose and total training volume as training intensity increased. These data suggest that exercise training intensity has no effect on the magnitude of training-induced increases in maximal oxygen uptake in young healthy human participants, but similar adaptations can be achieved in low training doses at higher exercise intensities than higher training doses of lower intensity (endurance training). PMID- 27182426 TI - Patient Characteristics and Prescribing Patterns Associated with Sofosbuvir Treatment for Chronic HCV Infection in a Commercially Insured Population. AB - BACKGROUND: In December 2013, the US Food and Drug Administration (FDA) approved sofosbuvir (Sovaldi) for the treatment of patients with chronic hepatitis C virus (HCV) infection. Given the potential "warehousing" of patients before the launch of sofosbuvir and the possibility that some patients and providers may have elected to continue deferring treatment in anticipation of more promising, interferon-free therapies in the pipeline, the early landscape for sofosbuvir treatment is difficult to ascertain. OBJECTIVE: To describe the demographics, clinical characteristics, and prescribing patterns associated with members requesting treatment with sofosbuvir in a commercially insured population in the United States. METHODS: A descriptive analysis was conducted using a randomly selected sample of commercially insured members who were identified as having a prior authorization request for sofosbuvir between March and June 2014. Member and provider characteristics, as well as treatment information, were collected using a prior authorization database from OptumRx, a national pharmacy care services company. The results were analyzed using descriptive statistics. RESULTS: A total of 338 members were selected for inclusion in the analysis. Chronic HCV genotype 1 infection was present in 74.3% of the members. Chronic HCV genotype 2, 3, or 4 was identified in 13.9%, 9.5%, and 1.2% of the members, respectively. Gastroenterologists and hepatologists accounted for 90% of providers. Among the 251 members with chronic HCV genotype 1, an interferon-free regimen was requested for 59.4% (N = 149) of them; the most frequently requested (51.4%) regimen for members with chronic HCV genotype 1 was the off-label combination of sofosbuvir plus simeprevir. Of the members with chronic HCV genotype 1, 19.1% had liver fibrosis equivalent to METAVIR stage F0 to F2 fibrosis, and 24.7% had liver fibrosis equivalent to METAVIR stage F3 to F4 fibrosis. For the remaining 56.2%, the degree of liver fibrosis was not known or could not be determined. Of the members with documented liver fibrosis, 49.6% were determined by liver biopsy. CONCLUSION: The results show that the initial prescribing of sofosbuvir often included the off-label interferon-free regimen of sofosbuvir plus simeprevir during the study period (of note, this combination regimen was approved by the FDA in November 2014, after the completion of the study period). The off-label prescribing pattern may be attributable to "warehousing" of patients who were awaiting more tolerable therapies. Furthermore, the limited utilization of noninvasive tests to assess liver fibrosis suggests that providers may benefit from additional education on these methods. Although this analysis provides insight into the treatment of patients with chronic HCV immediately after the launch of sofosbuvir in the United States, future research should reevaluate the treatment patterns of chronic HCV infection to capture recent advances in the treatment of this disease. PMID- 27182427 TI - Patient Preferences Regarding Rheumatoid Arthritis Therapies: A Conjoint Analysis. AB - BACKGROUND: Tofacitinib, an oral Janus kinase inhibitor approved for the treatment of rheumatoid arthritis (RA), provides patients with an alternative to subcutaneously or intravenously administered biologic disease-modifying antirheumatic drugs (DMARDs). Little is known about patient preference for novel RA treatments. OBJECTIVE: To investigate patient preferences for attributes associated with RA treatments. METHODS: A choice-based conjoint survey was mailed to 1400 randomly selected commercially insured patients (aged 21-80 years) diagnosed with RA, who were continuously enrolled from May 1, 2012, through April 30, 2013, and had >=2 medical claims for International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code 714.0 and no previous biologic DMARD use. Treatment attributes included route of administration; monthly out-of-pocket cost; frequency of administration; ability to reduce daily joint pain and swelling; likelihood of serious adverse events; improvement in the ability to perform daily tasks; and medication burden. Mean attribute importance scores were calculated after adjusting for patient demographics (eg, age, sex, years since diagnosis) using a hierarchical Bayes model. Patient preferences for each treatment attribute were ranked by the importance score. Part-worth utilities (ie, preference scores) were used to perform a conjoint market simulation. RESULTS: A total of 380 patients (response rate, 27.1%) returned the survey. Their mean age (+/- standard deviation) was 54.9 (+/- 9.3) years. Nonrespondents were 2 years younger (mean, 52.9 years; P = .002) but did not differ significantly from respondents in known clinical characteristics. After adjustment for demographic characteristics, mean patients' ranking of treatment attribute importance, in decreasing order, was route of administration, 34.1 (+/- 15.5); frequency of administration, 16.4 (+/- 6.8); serious adverse events, 12.0 (+/- 9.3); cost, 10.1 (+/- 6.2); medication burden, 9.8 (+/- 8.2); joint pain reduction, 8.9 (+/- 3.8); and daily tasks improvement, 8.8 (+/- 4.7). For the route of administration attribute, the part-worth utility was highest for the oral route. Conjoint simulation results showed that 56.4% of respondents would prefer an oral route of administration. CONCLUSION: Based on this survey completed by 380 patients with RA, commercially insured patients with RA consider the route of administration to be the most important attribute of their RA treatment. In this study, the majority (56.4%) of patients preferred the oral route of administration over other routes. Understanding patient preferences may help to inform provider and payer decisions in treatment selection that may enhance patient adherence to therapy. PMID- 27182428 TI - Inpatient Utilization and Costs for Medicare Fee-for-Service Beneficiaries with Heart Failure. AB - BACKGROUND: Although the medical and economic burden of heart failure in the United States is already substantial, it will likely grow as the population ages and life expectancy increases. Not surprisingly, most of the heart failure burden is borne by individuals aged >=65 years, many of whom are in the Medicare population. The population-based utilization and costs of inpatient care for Medicare beneficiaries with heart failure are not well understood by payers and providers. OBJECTIVE: To create a real-world view of utilization and costs associated with inpatient admissions, readmissions, and admissions to skilled nursing facilities among Medicare fee-for-service (FFS) beneficiaries with heart failure. METHODS: The study used the 2011 and 2012 Medicare 5% sample limited data set to perform a retrospective analysis of claims data. The look-back year that was used to identify certain patient characteristics was 2011, and 2012 was the analysis period for the study. Beneficiaries with heart failure were defined as those who had >=1 acute inpatient, emergency department, nonacute inpatient, or outpatient claims in 2012 containing an International Classification of Diseases, Ninth Revision code for heart failure. To be included in the study, beneficiaries with heart failure had to have eligibility for >=1 months in 2012 and in all 2011 months, with Part A and Part B eligibility in all the study months, and no enrollment in an HMO (Medicare Advantage plan). Utilization of inpatient admissions, inpatient readmissions, and skilled nursing facility admissions in 2012 were reported for Medicare FFS beneficiaries with heart failure and for all Medicare FFS beneficiaries. The costs for key metrics included all allowed Medicare payments in 2012 US dollars. RESULTS: The 2012 Medicare FFS population for this study consisted of 1,461,935 patients (1,301,545 without heart failure; 160,390 with heart failure); the heart failure prevalence was 11%. The Medicare-allowed cost per member per month (PMPM) was $3395 for a patient with heart failure, whereas the allowed cost for the total Medicare population was $1045 PMPM. The Medicare-allowed amounts for the population with heart failure accounted for 34% of the total annual Medicare FFS population allowed amounts. The heart failure population constituted 41.5%, 55.3%, and 49.5% of total Medicare FFS inpatient admissions, readmissions, and admissions to skilled nursing facilities, respectively. The costs of inpatient admissions, readmissions, and admissions to skilled nursing facilities among the heart failure population contributed $182 PMPM (17.5%), $58 PMPM (5.6%), and $46 PMPM (4.4%), respectively, to the total Medicare FFS population-allowed cost of $1045 PMPM. CONCLUSIONS: Medicare FFS beneficiaries with heart failure have high inpatient admission and readmission rates and generate substantial costs. Because a substantial portion of all inpatient admissions are for Medicare beneficiaries with heart failure, it is reasonable for hospitals in Medicare accountable care organizations to focus on more aggressive post-acute care management, including a focus on reducing readmissions for the population with heart failure. Our study findings highlight areas of high service utilization and cost for Medicare patients with heart failure that can be of value to Medicare, Medicare Advantage plans, and providers. PMID- 27182431 TI - Excited-state hydrogen atom abstraction initiates the photochemistry of beta-2' deoxycytidine. AB - Understanding the effects of ultraviolet radiation on nucleotides in solution is an important step towards a comprehensive description of the photochemistry of nucleic acids and their constituents. Apart from having implications for mutagenesis and DNA photoprotection mechanisms, the photochemistry of cytidines is a central element in UV-assisted syntheses of pyrimidine nucleotides under prebiotically plausible conditions. In this contribution, we present UV irradiation experiments of beta-2'-deoxycytidine in aqueous solution involving H D exchange followed by NMR spectroscopic analysis of the photoproducts. We further elucidate the outcome of these experiments by means of high-level quantum chemical calculations. In particular, we show that prolonged UV-irradiation of cytidine may lead to H-C1' hydrogen atom abstraction by the carbonyl oxygen atom of cytosine. This process may enable photoanomerisation and nucleobase loss, two previously unexplained photoreactions observed in pyrimidine nucleotides. PMID- 27182430 TI - Complete genome sequence of 'Halanaeroarchaeum sulfurireducens' M27-SA2, a sulfur reducing and acetate-oxidizing haloarchaeon from the deep-sea hypersaline anoxic lake Medee. AB - Strain M27-SA2 was isolated from the deep-sea salt-saturated anoxic lake Medee, which represents one of the most hostile extreme environments on our planet. On the basis of physiological studies and phylogenetic positioning this extremely halophilic euryarchaeon belongs to a novel genus 'Halanaeroarchaeum' within the family Halobacteriaceae. All members of this genus cultivated so far are strict anaerobes using acetate as the sole carbon and energy source and elemental sulfur as electron acceptor. Here we report the complete genome sequence of the strain M27-SA2 which is composed of a 2,129,244-bp chromosome and a 124,256-bp plasmid. This is the second complete genome sequence within the genus Halanaeroarchaeum. We demonstrate that genome of 'Halanaeroarchaeum sulfurireducens' M27-SA2 harbors complete metabolic pathways for acetate and sulfur catabolism and for de novo biosynthesis of 19 amino acids. The genomic analysis also reveals that 'Halanaeroarchaeum sulfurireducens' M27-SA2 harbors two prophage loci and one CRISPR locus, highly similar to that of Kulunda Steppe (Altai, Russia) isolate 'H. sulfurireducens' HSR2(T). The discovery of sulfur-respiring acetate-utilizing haloarchaeon in deep-sea hypersaline anoxic lakes has certain significance for understanding the biogeochemical functioning of these harsh ecosystems, which are incompatible with life for common organisms. Moreover, isolations of Halanaeroarchaeum members from geographically distant salt-saturated sites of different origin suggest a high degree of evolutionary success in their adaptation to this type of extreme biotopes around the world. PMID- 27182429 TI - A pragmatic guide to multiphoton microscope design. AB - Multiphoton microscopy has emerged as a ubiquitous tool for studying microscopic structure and function across a broad range of disciplines. As such, the intent of this paper is to present a comprehensive resource for the construction and performance evaluation of a multiphoton microscope that will be understandable to the broad range of scientific fields that presently exploit, or wish to begin exploiting, this powerful technology. With this in mind, we have developed a guide to aid in the design of a multiphoton microscope. We discuss source selection, optical management of dispersion, image-relay systems with scan optics, objective-lens selection, single-element light-collection theory, photon counting detection, image rendering, and finally, an illustrated guide for building an example microscope. PMID- 27182432 TI - Sexual dimorphism in myocardial acylcarnitine and triglyceride metabolism. AB - BACKGROUND: Cardiovascular disease is the leading cause of death among diabetic patients. Importantly, recent data highlight the apparent sexual dimorphism in the pathogenesis of cardiovascular disease in diabetics with respect to both frequency- and age-related risk factors. The disposition to cardiovascular disease among diabetic patients has been attributed, at least in part, to excess lipid supply to the heart culminating in lipotoxicity of the heart and downstream derangements. A confounding factor in obese animal models of diabetes is that increased peripheral lipid availability to the heart can induce cardio-metabolic remodeling independent of the underlying pathophysiology of diabetes, thus masking the diabetic phenotype. To that end, we hypothesized that the use of non obese diabetic (NOD) animal models will reveal metabolic signatures of diabetes in a sex-specific manner. METHODS: To test this hypothesis, male and female NOD Goto-Kakizaki (GK) rats were used to assess the expression profile of 84 genes involved in lipid metabolism. In parallel, targeted lipidomics analysis was performed to characterize sex differences in homeostasis of non-esterified fatty acids (NEFA), acylcarnitines (AC), and triglycerides (TG). RESULTS: Our analysis revealed significant sex differences in the expression of a broad range of genes involved in transport, activation, and utilization of lipids. Furthermore, NOD male rats exhibited enhanced oxidative metabolism and accumulation of TG, whereas female NOD rats exhibited reduced TG content coupled with accumulation of AC species. Multi-dimensional statistical analysis identified saturated AC16:0, AC18:0, and AC20:0 as dominant metabolites in mediating sex differences in AC metabolism. Confocal microscopy of rat cardiomyocytes exposed to AC14:0, AC16:0, and AC18:0 confirmed induction of ROS with AC18:0 being more potent followed by AC14:0. CONCLUSION: Overall, we demonstrate sex differences in myocardial AC and TG metabolism with implications for therapy and diagnosis of diabetic cardiovascular disease. PMID- 27182433 TI - Approaches for the prevention of graft-versus-host disease following hematopoietic cell transplantation. AB - Allogeneic hematopoietic cell transplantation (HCT) is an important therapeutic option for malignant and non-malignant diseases, but the more widespread application of the therapy remains limited by the occurrence of graft versus host disease (GVHD). GVHD results from immune-mediated injury by donor immune cells against tissues in the HCT recipient, and can be characterized as acute or chronic depending on the time of onset and site of organ involvement. The majority of efforts have focused on GVHD prevention. Calcineurin inhibitors are the most widely used agents and are included in almost all regimens. Despite current prophylaxis strategies, 40-70% of patients remain at risk for developing GVHD. Herein, we review standard and emerging therapies used in GVHD management. PMID- 27182434 TI - Circulating tumor DNA in hepatocellular carcinoma: trends and challenges. AB - Molecular characterization of individual patients' tumor cells is becoming increasingly important in offering effective treatment for patients in clinical practice. Recent advances in the field have indicated that circulating tumor DNA (ctDNA) has huge potential to serve as a biomarker for early detection and precision treatment as well as prognosis of hepatocellular carcinoma (HCC). As ctDNA in HCC patients harbors the molecular characteristics of HCC tumor cells, ctDNA analysis in the blood may be sufficient for convenient, non-invasive and accurate detection, providing information for HCC diagnosis, treatment and prognosis. In this review, we will summarize and discuss current trends and challenges of ctDNA application in HCC. PMID- 27182435 TI - NMR relaxation and structural elucidation of peptides in the presence and absence of trifluoroethanol illuminates the critical molecular nature of integrin alphavbeta6 ligand specificity. AB - Integrin alphavbeta6 is an important emerging target for both imaging and therapy of cancer that requires specific ligands based on Arg-Gly-Asp (RGD) peptides. There remains little correlation between integrin-RGD ligand specificity despite studies suggesting an RGD-turn-helix ligand motif is required. Here, we describe the application of 15N NMR relaxation analyses and structure determination of alphavbeta6 peptide ligands in the presence and absence of trifluoroethanol (TFE) to identify their critical molecular nature that influences specificity, interaction and function. Two linear peptides; one known to demonstrate alphavbeta6 specificity (FMDV2) and the other based on a natural RGD ligand (LAP2), were compared to two additional peptides based on FMDV2 but cyclised in different positions using a disulphide bond (DBD1 and DBD2). The cyclic adaptation in DBD1 produces a significant alteration in backbone dynamic properties when compared to FMDV2; a potential driver for the loss in alphavbeta6 specificity by DBD1. The importance of ligand dynamics are highlighted through a comprehensive reduced spectral density and ModelFree analysis of peptide 15N NMR relaxation data and suggest alphavbeta6 specificity requires the formation of a structurally rigid helix preceded by a RGD motif exhibiting slow internal motion. Additional observations include the effect of TFE/water viscosity on global NMR dynamics and the advantages of using spectral density NMR relaxation data to estimate correlation times and motional time regimes for peptides in solution. PMID- 27182436 TI - Optimising selective excitation pulses to maximise saturation transfer difference NMR spectroscopy. AB - A simple method is presented that optimizes the STD NMR Gaussian pulse to deliver significant increases in STD amplification factors with minimal perturbation of the ligand. This approach is practically demonstrated using the wheat-germ agglutinin/N-acetyl-D-glucosamine protein-ligand system. PMID- 27182437 TI - Interactive graphics for functional data analyses. AB - Although there are established graphics that accompany the most common functional data analyses, generating these graphics for each dataset and analysis can be cumbersome and time consuming. Often, the barriers to visualization inhibit useful exploratory data analyses and prevent the development of intuition for a method and its application to a particular dataset. The refund.shiny package was developed to address these issues for several of the most common functional data analyses. After conducting an analysis, the plot shiny() function is used to generate an interactive visualization environment that contains several distinct graphics, many of which are updated in response to user input. These visualizations reduce the burden of exploratory analyses and can serve as a useful tool for the communication of results to non-statisticians. PMID- 27182438 TI - Model-free methods to study membrane environmental probes: a comparison of the spectral phasor and generalized polarization approaches. AB - In this note, we present a discussion of the advantages and scope of model-free analysis methods applied to the popular solvatochromic probe LAURDAN, which is widely used as an environmental probe to study dynamics and structure in membranes. In particular, we compare and contrast the generalized polarization approach with the spectral phasor approach. To illustrate our points we utilize several model membrane systems containing pure lipid phases and, in some cases, cholesterol or surfactants. We demonstrate that the spectral phasor method offers definitive advantages in the case of complex systems. PMID- 27182439 TI - Combination delivery of Adjudin and Doxorubicin via integrating drug conjugation and nanocarrier approaches for the treatment of drug-resistant cancer cells. AB - Combination therapy has been regarded as a potent strategy to overcome multidrug resistance (MDR). In this study, we adopt Adjudin (ADD), a mitochondria inhibitor, and Doxorubicin (DOX), a common chemo-drug, to treat drug-resistant cancer cells (MCF-7/ADR) in combination. Given the different physico-chemical properties of ADD and DOX, we develop a novel drug formulation (ADD-DOX (M)) by integrating drug conjugation and nanocarrier approaches to realize the co delivery of the two drugs. We demonstrate the conjugation of ADD and DOX via formation of an acid-sensitive hydrazone bond, and then the encapsulation of ADD DOX conjugates by DSPE-PEG2000 micelles with high drug encapsulation efficiency and well-controllable drug loading efficiency. The obtained ADD-DOX (M) micelles are found to be stable under physiological conditions, but can rapidly release drugs within acidic environments. Following cellular experiments confirm that ADD DOX (M) vehicles can be internalized by MCF-7/ADR cancer cells through an endocytic pathway and exist within the moderate acidic endolysosomes, thus accelerating the hydrolysis of ADD-DOX and the release of free ADD and DOX. As a result, the ADD-DOX (M) formulation exhibits an excellent anti-MDR effect. In summary, we for the first time report the combinational use of ADD and DOX with an effective co-delivery strategy for the treatment of MDR cancer cells. PMID- 27182440 TI - Topography measurements and applications in ballistics and tool mark identifications. AB - The application of surface topography measurement methods to the field of firearm and toolmark analysis is fairly new. The field has been boosted by the development of a number of competing optical methods, which has improved the speed and accuracy of surface topography acquisitions. We describe here some of these measurement methods as well as several analytical methods for assessing similarities and differences among pairs of surfaces. We also provide a few examples of research results to identify cartridge cases originating from the same firearm or tool marks produced by the same tool. Physical standards and issues of traceability are also discussed. PMID- 27182441 TI - Studies on the laccase-mediated decolorization, kinetic, and microtoxicity of some synthetic azo dyes. AB - BACKGROUND: Enzymatic elimination of synthetic dyes, one of the most environmentally hazardous chemicals, has gained a great interest during the two last decades. The present study was performed to evaluate the decolorization and detoxification potential of the purified laccase of Paraconiothyrium variabile in both non-assisted and hydroxybenzotriazole-aided form against six azo dyes. RESULTS: The obtained results showed that Acid Orange 67, Disperse Yellow 79, Basic Yellow 28, Basic Red 18, Direct Yellow 107, and Direct Black 166 were decolorized up to 65.3, 53.3, 46.7, 40.7, 34, and 26.2 %, respectively, after 1 h treatment with laccase (0.5 U/mL). Addition of HBT up to 5 mM enhanced decolorization percent of all the investigated dyes. The results of kinetic study introduced the monoazo dye of Acid Orange 67 as the most suitable substrate for laccase with K m of 0.49 mM and V max of 189 mmol/min/mg. Evaluation the toxic effect of laccase-treated dye sample based on the growth inhibition of standard bacterial strains revealed decrease in toxicity of all applied dyes after treatment by laccase. CONCLUSIONS: Application of the P. variabile laccase as biocatalyst efficiently decreased the toxicity of all studied synthetic azo dyes. PMID- 27182442 TI - Employment and occupation effects on late-life depressive symptoms among older Koreans: a cross-sectional population survey. AB - BACKGROUND: The present study investigated the prevalence of depressive symptoms in older Koreans and identified associations between depressive symptoms and occupational factors. METHODS: Data from the Korean National Health and Nutrition Examination Survey V (2010-2012) were used to analyze 7320 participants aged 55 years or older. Complex sample logistic regression analysis was performed after adjusting general characteristics to determine associations between depressive symptoms and occupational factors. RESULTS: Among older Korean men, the prevalence of depressive symptoms in the employed and the non-employed groups were 9.9 % and 13.7 %, respectively. Employment status was significantly associated with depressive symptoms after adjusting for general factors (OR: 0.69, 95 % CI: 0.49-0.97). Among older Korean women, the prevalence of depressive symptoms in the employed and the non-employed groups were 17.4 % and 20.3 %, respectively, but employment status was not significantly associated with depressive symptoms. Second skill level occupational groups (clerks, plant and machine operators) in particular showed significantly lower prevalence of depressive symptoms than the non-employed group of men (9.3 % vs 13.7 %). By occupation type, the odds ratios were 0.31 (95 % CI: 0.10-0.97, clerks) and 0.47 (95 % CI: 0.23-0.86, plant and machine operators) adjusting for general factors. CONCLUSIONS: The employed group showed lower late-life depressive symptom prevalence than the non-employed group among older Korean men. In addition some second skill level occupations (clerks, plant and machine operators) were significantly associated with a lower risk of depressive symptoms after adjusting for general factors in older Korean men. PMID- 27182443 TI - The association between blood cadmium level, frequency and amount of gejang (marinated crab) intake. AB - BACKGROUND: Gejang (marinated crab) is a favorite traditional food and a main source of crab intake among Koreans. The present study aimed to identify the possibility of cadmium inflow to the body through gejang; accordingly, the relationship between gejang intake frequency and amount, and blood cadmium concentrations was investigated. METHODS: Using data from the first Korea National Health and Nutrition Examination Survey in the sixth period in 2013, means and standard errors of blood cadmium concentrations in relation to gejang intake frequency and amount, as well as the monthly intake of gejang, were obtained from 1381 participants for whom data regarding blood cadmium concentration measurements was available. RESULTS: After adjustment for confounding factors, a gejang intake frequency of four or fewer times per week and a monthly intake of 200 cm(3) or less had no significant effect on blood cadmium concentrations. However, participants with gejang intake of at least five times per week had a weighted mean cadmium concentration of 2.12 MUg/L (p < 0.001), and participants who had a gejang monthly intake of more than 200 cm(3) had a weighted mean cadmium concentration of 1.76 MUg/L (p < 0.001). CONCLUSION: These results suggest that to minimize the effect of gejang consumption on blood cadmium level, gejang intake should be limited to four or less times per week and 200 cm(3) or less per month. Weekly intake of at least five times and monthly intake of more than 200 cm(3) may increase blood cadmium levels. PMID- 27182444 TI - Perspectives on optimizing care of patients in multidisciplinary chronic kidney disease clinics. AB - PURPOSE OF REVIEW: To summarize a jointly held symposium by the Canadian Society of Nephrology (CSN), the Canadian Association of Nephrology Administrators (CANA), and the Canadian Kidney Knowledge Translation and Generation Network (CANN-NET) entitled "Perspectives on Optimizing Care of Patients in Multidisciplinary Chronic Kidney Disease (CKD) Clinics" that was held on April 24, 2015, in Montreal, Quebec. SOURCES OF INFORMATION: The panel consisted of a variety of members from across Canada including a multidisciplinary CKD clinic patient (Randall Russell), nephrology fellow (Dr. David Collister), geriatrician (Dr. Josee Verdon), and nephrologists (Dr. Monica Beaulieu, Dr. Adeera Levin). FINDINGS: The objectives of the symposium were (1) to gain an understanding of the goals of care for CKD patients, (2) to gain an appreciation of different perspectives regarding optimal care for patients with CKD, (3) to examine the components required for optimal care including education strategies, structures, and tools, and (4) to describe a framework and metrics for CKD care which respect patient and system needs. This article summarizes the key concepts discussed at the symposium from a patient and physician perspectives. Key messages include (1) understanding patient values and preferences is important as it provides a framework as to what to prioritize in multidisciplinary CKD clinic and provincial renal program models, (2) barriers to effective communication and education are common in the elderly, and adaptive strategies to limit their influence are critical to improve adherence and facilitate shared decision-making, (3) the use of standardized operating procedures (SOPs) improves efficiency and minimizes practice variability among health care practitioners, and (4) CKD scorecards with standardized system processes are useful in approaching variability as well as measuring and improving patient outcomes. LIMITATIONS: The perspectives provided may not be applicable across centers given the differences in patient populations including age, ethnicity, culture, language, socioeconomic status, education, and multidisciplinary CKD clinic structure and function. IMPLICATIONS: Knowledge transmission by collaborative interprovincial and interprofessional networks may play a role in facilitating optimal CKD care. Validation of system and clinic models that improve outcomes is needed prior to disseminating these best practices. PMID- 27182446 TI - Mesenchymal stem cell therapy for acute radiation syndrome. AB - Acute radiation syndrome affects military personnel and civilians following the uncontrolled dispersal of radiation, such as that caused by detonation of nuclear devices and inappropriate medical treatments. Therefore, there is a growing need for medical interventions that facilitate the improved recovery of victims and patients. One promising approach may be cell therapy, which, when appropriately implemented, may facilitate recovery from whole body injuries. This editorial highlights the current knowledge regarding the use of mesenchymal stem cells for the treatment of acute radiation syndrome, the benefits and limitations of which are under investigation. Establishing successful therapies for acute radiation syndrome may require using such a therapeutic approach in addition to conventional approaches. PMID- 27182447 TI - Bell's palsy at high altitude -- an unsuspected finding. AB - BACKGROUND: Bell's palsy is a common condition seen in clinical practice. The aetiology of this condition is not clearly defined and neuroimaging is essential to exclude intracranial causes of infra-nuclear facial palsy. CASE PRESENTATION: We report a young soldier, who presented with Bell's palsy and neuroimaging revealed an unsuspected finding of multiple intracranial calcifications. Detailed evaluation revealed the additional diagnosis of vitamin D deficiency and secondary hyperparathyroidism due to lack of sun exposure at high altitude area. CONCLUSION: The health care practitioners, looking after the soldiers at high altitude areas should be aware of the measures to prevent vitamin D deficiency. Intracranial calcifications are uncommon in hyperparathyroidism and Bell's palsy. PMID- 27182448 TI - Determinants of undernutrition among children aged 6 to 59 months in rural Zambezia Province, Mozambique: Results of two population-based serial cross sectional surveys. AB - BACKGROUND: While many countries are transitioning from epidemics of undernutrition to overnutrition, Mozambique's very high 44% prevalence of stunting in children under age 5 years is cause for serious concern. METHODS: We conducted two population-based cross-sectional surveys of ~4000 female heads of households each in Zambezia Province, Mozambique from August-September 2010 (Baseline) and April-May 2014 (Endline) as part of the USAID funded Strengthening Communities through Integrated Programs (SCIP) grant. Anthropometric measurements were collected on 560 children aged 6-59 months at Baseline and 912 children at Endline and classified as: "stunted," a height-for-age z-score less than -2; "wasted," weight-for-height z-score less than -2; and "underweight," weight-for age z-score less than -2. Descriptive statistics and logistic regression using Stata 13.1 were used to examine factors associated with undernutrition. RESULTS: Of children under age five years, 43% were undernourished in 2010 and 55% in 2014. The most common form of undernutrition was stunting (39% in 2010, 51% in 2014), followed by underweight (13% in both 2010 and 2014), and wasting (7% in 2010, 5% in 2014). Child's age was found to have a non-linear association with stunting. Vitamin A supplementation was associated with a 31% (p=0.04) decreased odds of stunting. Children who were exclusively breastfed for at least six months had an 80% (p=0.02) lower odds of wasting in 2014 and 57% (p=0.05) decreased odds of being underweight in 2014. Introducing other foods after age six months was associated with a five-fold increased odds of wasting in 2014 (p=0.02); household food insecurity was associated with wasting (OR=2.08; p=0.03) and underweight in 2010 (OR=2.31; p=0.05). Children whose mother washed her hands with a cleaning agent had a 40% (p=0.05) decreased odds of being underweight. Surprisingly, per point increase in household dietary diversity score, children had 12% greater odds of being stunted in 2010 (p=0.01) but 9% decreased odds of being underweight in 2014 (p=0.02). CONCLUSIONS: A combination of household and individual level factors was associated with undernutrition. As such, employment of multidimensional interventions should be considered to decrease undernutrition in children under five years old. PMID- 27182450 TI - CYP-epoxygenase metabolites of docosahexaenoic acid protect HL-1 cardiac cells against LPS-induced cytotoxicity Through SIRT1. AB - Bacterial LPS is an environmental toxin capable of promoting various cardiac complications. Current evidence suggests that LPS-induced myocardial dysfunction emerges as a consequence of compromised quality of cardiac mitochondria. Docosahexaenoic acid (DHA, 22:6n3) is an n-3 polyunsaturated fatty acid (PUFA), which produces a broad spectrum of intrinsic physiological effects including regulation of cell survival and death mechanisms. Although, numerous studies revealed fundamentally beneficial effects of DHA on cardiovascular system, it remains unknown whether these effects were produced by DHA or one of its possibly more potent metabolites. Emerging evidence indicates that cytochrome P450 (CYP) epoxygenase metabolites of DHA, epoxydocosapentaenoic acids (EDPs), produce more potent biological activity compared to its precursor DHA. In this study we investigated whether DHA and its metabolite 19,20-EDP could protect HL-1 cardiac cells against LPS-induced cytotoxicity. We provide evidence that exogenously added or DHA-derived EDPs promote mitochondrial biogenesis and function in HL-1 cardiac cells. Our results illustrate the CYP epoxygenase metabolite of DHA, 19,20-EDP, confers extensive protection to HL-1 cardiac cells against LPS-induced cytotoxicity via activation of SIRT1. PMID- 27182451 TI - A Clinical Trial of Translation of Evidence Based Interventions to Mobile Tablets and Illness Specific Internet Sites. AB - This article describes a method to translate an evidence based health care intervention to the mobile environment. This translation assisted patient participants to: avoid life threatening infections; monitor emotions and fatigue; keep involved in healthy activities. The mobile technology also decreased costs by reducing for example travel to visit health care providers. Testing of this translation method and its use by comparison groups of patients adds to the knowledge base for assessing technology for its impact on health outcome measures. The challenges and workflow of designing materials for the mobile format are described. Transitioning clinical trial verified interventions, previously provided in person to patients, onto tablet and internet platforms is an important process that must be evaluated. In this study, our evidence based guide's intravenous (IV) homeCare interventions (IVhomeCare) were delivered via Apple iPad miniTM tablet audiovisual instruction / discussion sessions and on a website. Each iPad audiovisual session (n = 41), included three to five families, a mental health specialist, and healthcare professionals. Patients and their family caregivers readily learned to use the wireless mobile tablets, and the IVhomeCare interventions, as described here, were successfully translated onto these mobile technology platforms. Using Likert scale responses on a questionnaire (1 = not helpful and 5 = very helpful) participants indicated that they gained problem solving skills for home care through iPad group discussion (M = 4.60, SD = 0.60). The firewall protected videoconferencing in real time with multiple healthcare professionals effectively allowed health history taking and visual inspection of the patient's IV insertion site for signs of infection. Supportive interactions with peer families on videoconferencing were documented during discussions. Discussion topics included low moods, fatigue, infection worry, how to maintain independence, and need for support from others with their same lifelong IV experiences. The visual family interactions, discussions with professionals, and the iPad internet links were highly rated. Mobile distance care delivery can result in saved time and money for both healthcare professionals and families. PMID- 27182449 TI - A review of 3D image-based dosimetry, technical considerations and emerging perspectives in 90Y microsphere therapy. AB - Yttrium-90 radioembolization (90Y-RE) is a well-established therapy for the treatment of hepatocellular carcinoma (HCC) and also of metastatic liver deposits from other malignancies. Nuclear Medicine and Cath Lab diagnostic imaging takes a pivotal role in the success of the treatment, and in order to fully exploit the efficacy of the technique and provide reliable quantitative dosimetry that are related to clinical endpoints in the era of personalized medicine, technical challenges in imaging need to be overcome. In this paper, the extensive literature of current 90Y-RE techniques and challenges facing it in terms of quantification and dosimetry are reviewed, with a focus on the current generation of 3D dosimetry techniques. Finally, new emerging techniques are reviewed which seek to overcome these challenges, such as high-resolution imaging, novel surgical procedures and the use of other radiopharmaceuticals for therapy and pre therapeutic planning. PMID- 27182453 TI - Network of remote and local protein dynamics in dihydrofolate reductase catalysis. AB - Molecular dynamics calculations and bionformatic studies of dihydrofolate reductase (DHFR) have suggested a network of coupled motions across the whole protein that is correlated to the reaction coordinate. Experimental studies demonstrated that distal residues G121, M42 and F125 in E. coli DHFR participate in that network. The missing link in our understanding of DHFR catalysis is the lack of a mechanism by which such remote residues can affect the catalyzed chemistry at the active site. Here, we present a study of the temperature dependence of intrinsic kinetic isotope effects (KIEs) that indicates synergism between a remote residue in that dynamic network, G121, and the active site's residue I14. The intrinsic KIEs for the I14A-G121V double mutant showed steeper temperature dependence (DeltaEa(T-H)) than expected from comparison of the wild type and two single mutants. That effect was non-additive, i.e., DeltaEa(T H)G121V +DeltaEa(T-H) I14A < DeltaEa(T-H) double mutant, which indicates a synergism between the two residues. This finding links the remote residues in the network under investigation to the enzyme's active site, providing a mechanism by which these residues can be coupled to the catalyzed chemistry. This experimental evidence validates calculations proposing that both remote and active site residues constitute a network of coupled promoting motions correlated to the bond activation step (C-H->C hydride transfer in this case). Additionally, the effect of I14A and G121V mutations on single turnover rates was additive rather than synergistic. Although single turnover rate measurements are more readily available and thus more popular than assessing intrinsic kinetic isotope effects, the current finding demonstrates that for these rates, which in DHFR reflect several microscopic rate constants, can fall short of revealing the nature of the C-H bond activation per se. PMID- 27182454 TI - Lower Plasma Zinc Levels in Hyperglycemic People Living with HIV in the MASH cohort. AB - BACKGROUND: Zinc deficiency is prevalent in HIV and hyperglycemic patients. Antiretroviral therapy (ART) is a treatment to control HIV progression; however it increases the risk for hyperglycemia. The objective of this study was to assess the plasma zinc levels in hyperglycemic people living with HIV (PLWH). METHODS: Secondary analysis was conducted on the data from the Miami Adult Studies in HIV (MASH) cohort in Florida. Patients were categorized into hyperglycemic group (fasting blood glucose >=100 mg/dL) and normal group (<100 mg/dL). RESULTS: Plasma zinc status and CD4 levels were lower in the hyperglycemic group, however the difference was not significant. There was a greater percentage of plasma zinc deficiency in the hyperglycemic group (69%) compared to the normoglycemic group (64%). DISCUSSION: Although not statistically significant, related biomarkers such as plasma zinc levels and CD4 levels were lower in the hyperglycemic group. This may be due to the role zincplays in the immune system. Due to the fact that there was a higher percentage of plasma zinc deficiency in the hyperglycemic group (69%) compared to the normoglycemic group (64%), it is important to monitor and manage blood glucose levels to minimize complications. Our findings along with previous findings suggest that zinc supplementation may benefit hyperglycemic PLWH. PMID- 27182452 TI - A Brief Chronicle of CD4 as a Biomarker for HIV/AIDS: A Tribute to the Memory of John L. Fahey. AB - Foundational cellular immunology research of the 1960s and 1970s, together with the advent of monoclonal antibodies and flow cytometry, provided the knowledge base and the technological capability that enabled the elucidation of the role of CD4 T cells in HIV infection. Research identifying the sources and magnitude of variation in CD4 measurements, standardized reagents and protocols, and the development of clinical flow cytometers all contributed to the feasibility of widespread CD4 testing. Cohort studies and clinical trials provided the context for establishing the utility of CD4 for prognosis in HIV-infected persons, initial assessment of in vivo antiretroviral drug activity, and as a surrogate marker for clinical outcome in antiretroviral therapeutic trials. Even with sensitive HIV viral load measurement, CD4 cell counting is still utilized in determining antiretroviral therapy eligibility and time to initiate therapy. New point of care technologies are helping both to lower the cost of CD4 testing and enable its use in HIV test and treat programs around the world. PMID- 27182455 TI - Myocardial Strain and Strain Rate in Kawasaki Disease: Range, Recovery, and Relationship to Systemic Inflammation/Coronary Artery Dilation. AB - BACKGROUND: Kawasaki Disease (KD), a systemic vasculitis of medium sized vessels, is the most common cause of acquired heart disease among children in the developed world. Some KD patients demonstrate echocardiographic evidence of depressed myocardial mechanics. However, the incidence, etiology, and reversibility of abnormal mechanics in KD patients remain undefined. METHODS AND RESULTS: We retrospectively studied 41 KD patients and measured myocardial strain and strain rate by velocity vector imaging from pre-treatment and convalescent echocardiograms. Pre-treatment procalcitonin, C-reactive protein (CRP), and coronary artery z-scores were obtained in all patients and compared between the groups with preserved versus depressed acute phase mechanics. The change in mechanics between the acute and convalescent phases was also assessed. Patients with initially low longitudinal strain improved by the convalescent period (mean difference - 4.0%; p<0.005) with the greatest improvement occurring in patients with the lowest initial strain (-7.3%; p<0.05). Patients with higher initial strain did not change significantly by the convalescent period. Patients with lower longitudinal and circumferential strain demonstrated higher median procalcitonin levels (1.2 vs. 0.3 ng/mL; p<0.05 and 1.8 vs. 0.4 ng/mL; p<0.05 respectively) and a trend towards higher CRP, but no difference in coronary artery z-scores. Strain rate was not associated with inflammatory markers or coronary artery z-scores. CONCLUSIONS: The range of strain found in our cohort was large. Improvement in mean strain was driven primarily by patients with lower initial strain. Lower strain was associated with increased markers of systemic inflammation, but not proximal coronary artery changes. PMID- 27182457 TI - Using an Instructional Design Model to Teach Medical Procedures. AB - Educators are often tasked with developing courses and curricula that teach learners how to perform medical procedures. This instruction must provide an optimal, uniform learning experience for all learners. If not well designed, this instruction risks being unstructured, informal, variable amongst learners, or incomplete. This article shows how an instructional design model can help craft courses and curricula to optimize instruction in performing medical procedures. Educators can use this as a guide to developing their own course instruction. PMID- 27182458 TI - Induction of Cancer Cell Death by Hyaluronic Acid-Mediated Uptake of Cytochrome C. AB - Effective cancer treatment needs both, passive and active targeting approaches, to achieve highly specific drug delivery to the target cells while avoiding cytotoxicity to normal cells. Protein drugs are useful in this context because they can display excellent specificity and potency. However, their use in therapeutic formulations is limited due to their physical and chemical instability during storage and administration. Polysaccharides have been used to stabilize proteins during formulation and delivery. To accomplish both, stabilization and targeting simultaneously, the apoptosis-inducing protein cytochrome c (Cyt c) was modified with the polysaccharide hyaluronic acid (HA) because its corresponding receptor CD44 is overexpressed in many cancers. Cyt c HA bioconjugates were formed using low and high molecular weight HA (8 kDa and 1 MDa) with a resultant Cyt c loading percentage of 4%. Circular dichroism and a cell-free caspase assay showed minor structural changes and high bioactivity (more than 80% caspase activation) of Cyt c, respectively, after bioconjugate formation. Two CD44-positive cancer cells lines, HeLa and A549 cells, and two CD44-negative normal cell lines, Huvec and NIH-3T3 cells, were incubated with the samples to assess selectivity and cytotoxicity. After 24 h of incubation with the samples, cancer cell viability was reduced at least 3-fold while CD44-negative control cell lines remained minimally affected. Fluorescence imaging confirmed selective internalization of the Cyt c-HA construct by CD44-positive cancer cell lines. These results demonstrate the development of a drug delivery system that incorporates passive and active targeting which is essential for cancer treatment. PMID- 27182459 TI - A Qualitative Examination of Stigma Among Formerly Incarcerated Adults Living With HIV. AB - The over-representation of people with stigmatized characteristics in the U.S. criminal justice population, including adults living with HIV, makes formerly incarcerated adults susceptible to multiple stigmas. Yet, the experience of HIV related stigma, especially among individuals who have an additional compromising status in society (i.e., a criminal record) is understudied. This study used qualitative data from 30 interviews with formerly incarcerated adults living with HIV to explore the contexts within which one of these statuses becomes more salient than another for these individuals. Anticipated stigma was the primary barrier to disclosure of either status. The salience of anticipated stigma depended on the context within which disclosure may occur, including social interactions, employment, and engaging in HIV care. Communities with a high prevalence of HIV and incarceration, and health care providers within those communities should be targeted for stigma reduction efforts. Practitioners should work to empower individuals living with HIV, especially in the face of multiple potential stigmas. PMID- 27182456 TI - Role of Serum Biomarkers in Early Detection of Non-Alcoholic Steatohepatitis and Fibrosis in West Virginian Children. AB - BACKGROUND: Obesity, an epidemic among West Virginia children, as well as insulin resistance (IR), is well-established contributors to nonalcoholic steatohepatitis (NASH). Progression of NASH can lead to hepatic fibrosis and cirrhosis, making early detection imperative. The standard for diagnosing NASH is histologically via liver biopsy, which is highly invasive and generally contraindicated in children. By studying serum biomarkers associated with NASH, we aim to identify high risk children who can benefit from a less invasive, alternative approach to the early detection of NASH. METHODS: Seventy one children were prospectively recruited and divided into 3 groups: normal weight without IR (control), obese without IR, and obese with IR. Serum samples were drawn for each patient and biomarker levels were assessed via ELISA kits. RESULTS: Obese without IR and obese with IR patients had significantly elevated levels of lipid metabolism and accumulation markers (FGF-21, NEFA, FATP5, ApoB), oxidative stress markers (dysfunctional HDL, 8-Isoprostane), inflammatory markers(dysfunctional HDL, CK 18) and apoptosis markers (CK-18) compared to control patients (p<0.02). Bilirubin (an antioxidant) was significantly decreased in the obese without IR and obese with IR patients compared to control (p<0.02). CONCLUSION: This study showed a correlation between obesity, IR, and biomarkers associated with NASH in pediatrics patients from West Virginia, with obese with IR patients showing the strongest correlation. These findings support the clinical application of these serum biomarkers as a less invasive method for early detection of NASH and hepatic fibrosis. PMID- 27182460 TI - A Multivariate Timeseries Modeling Approach to Severity of Illness Assessment and Forecasting in ICU with Sparse, Heterogeneous Clinical Data. AB - The ability to determine patient acuity (or severity of illness) has immediate practical use for clinicians. We evaluate the use of multivariate timeseries modeling with the multi-task Gaussian process (GP) models using noisy, incomplete, sparse, heterogeneous and unevenly-sampled clinical data, including both physiological signals and clinical notes. The learned multi-task GP (MTGP) hyperparameters are then used to assess and forecast patient acuity. Experiments were conducted with two real clinical data sets acquired from ICU patients: firstly, estimating cerebrovascular pressure reactivity, an important indicator of secondary damage for traumatic brain injury patients, by learning the interactions between intracranial pressure and mean arterial blood pressure signals, and secondly, mortality prediction using clinical progress notes. In both cases, MTGPs provided improved results: an MTGP model provided better results than single-task GP models for signal interpolation and forecasting (0.91 vs 0.69 RMSE), and the use of MTGP hyperparameters obtained improved results when used as additional classification features (0.812 vs 0.788 AUC). PMID- 27182463 TI - Sexual Decision Making in the Absence of Choice: The African American Female Dating Experience. AB - Although links between low mate availability and increased HIV and STI risk for African American women have been documented in the literature, we know little about the impact of limited mate choices on the quality of relationships between Black men and women and how these relationship dynamics impact risk for young Black women. We conducted a qualitative study with African American female young adults (N=12) to explore the perceived impact of structural forces on African American female young adults' dating and sexual behavior. Participants reported (1) perceptions of Black men as untrustworthy and manipulative, (2) the limited and often negative roles for Black men in the larger Black community, and (3) heterosexual relationships in the Black community as increasingly influenced by economics and commerce. Recommendations for HIV prevention interventions that include micro and macro level approaches are discussed. PMID- 27182462 TI - Visible Red Light Emitting Diode Photobiomodulation for Skin Fibrosis: Key Molecular Pathways. AB - Skin fibrosis, also known as skin scarring, is an important global health problem that affects an estimated 100 million persons per year worldwide. Current therapies are associated with significant side effects and even with combination therapy, progression, and recurrence is common. Our goal is to review the available published data available on light-emitting diode-generated (LED) red light phototherapy for treatment of skin fibrosis. A search of the published literature from 1 January 2000 to present on the effects of visible red light on skin fibrosis, and related pathways was performed in January 2016. A search of PubMed and EMBASE was completed using specific keywords and MeSH terms. "Fibrosis" OR "skin fibrosis" OR "collagen" was combined with ("light emitting diode," "LED," "laser," or "red light"). The articles that were original research studies investigating the use of visible red light to treat skin fibrosis or related pathways were selected for inclusion. Our systematic search returned a total of 1376 articles. Duplicate articles were removed resulting in 1189 unique articles, and 133 non-English articles were excluded. From these articles, we identified six articles related to LED effects on skin fibrosis and dermal fibroblasts. We augmented our discussion with additional in vitro data on related pathways. LED phototherapy is an emerging therapeutic modality for treatment of skin fibrosis. There is a growing body of evidence demonstrating that visible LED light, especially in the red spectrum, is capable of modulating key cellular characteristic associated with skin fibrosis. We anticipate that as the understanding of LED-RL's biochemical mechanisms and clinical effects continue to advance, additional therapeutic targets in related pathways may emerge. We believe that the use of LED-RL, in combination with existing and new therapies, has the potential to alter the current treatment paradigm of skin fibrosis. There is a current lack of clinical trials investigating the efficacy of LED-RL to treat skin fibrosis. Randomized clinical trials are needed to demonstrate visible red light's clinical efficacy on different types of skin fibrosis. PMID- 27182464 TI - Factors Associated with Unmet Needs among African-American Dementia Care Providers. AB - Racial and ethnic minorities currently comprise 20% of the U.S. population; in 2050, this figure is expected to rise to 42%. As a result, Alzheimer's disease (AD), the 5th leading cause of death for people aged 65 and older, is likely to increase in these groups. Most dementia caregiving for these populations comes from family and friends, especially among families with lower socioeconomic status. A convenience sample of 30 African-American dementia caregivers was interviewed to determine unmet needs. Participants expressed a limited desire for formal services, such as support groups, legal advice, case management, and homemaker services. Instead, commonly expressed needs were daytime respite care and especially a desire for family and social support. Many caregivers expressed a need for other family members to share responsibility in the process; therefore, methods for caregiver support that address multiple family members in care provision may be beneficial for this group. PMID- 27182461 TI - Two Decades of Teledermatology: Current Status and Integration in National Healthcare Systems. AB - Teledermatology, originating in 1995, has been one of the first telemedicine services to see the light of day. Two decades of teledermatology research is summarized in this review. A literature search was conducted in PubMed. Search terms included "teledermatology," "teledermoscopy," "tele wound care," "telederm*," "(dermatology OR dermoscopy OR wound care OR skin) AND (telemedicine OR ehealth or mhealth OR telecare OR teledermatology OR teledermoscopy)." Inclusion criteria were (i) Dutch or English written papers and (ii) publication year from 2011 to present or (iii) (systematic) reviews with publication year before 2011. One hundred fourteen publications and 14 (systematic) reviews were included for full text reading. Focus of this review is on the following outcomes: (i) actors (primary, secondary, tertiary), (ii) purposes (consultation, triage, follow-up, education) and subspecialties (tele-wound care, burn care, teledermoscopy (teledermatoscopy), teledermatopathology, and mobile teledermatology), (iii) delivery modalities and technologies (store and forward, real-time interactive, and hybrid modalities using web-based systems, email, mobile phones, tablets, or videoconferencing equipment), (iv) business models, (v) integration of teledermatology into national healthcare systems, (vi) preconditions and requirements for implementation (security, ethical issues, responsibility, reimbursement, user satisfaction, technique, and technology standards), and (vii) added value. To conclude, teledermatology is an efficient and effective healthcare service compared to in-person care. Teledermatology reduces patients' travel time and waiting time, avoids (unnecessary) dermatologic visits, and improves access of care to underserved patients. PMID- 27182465 TI - Brain Metastases as Presenting Feature in 'Burned Out' Testicular Germ Cell Tumor. AB - Testicular germ cell tumors (TGCTs) are the most common malignancy in males aged 20 to 39, and the incidence is increasing. TGCTs have a tendency to grow rapidly with a high risk of metastatic spread. TGCTs generally present with a palpable testicular mass, yet may present less commonly with symptoms arising from metastatic disease. A 24-year-old otherwise healthy male presented with progressive headaches. Initial imaging reported a single mass in the right frontal lobe. Complete surgical resection revealed suspicion for metastatic poorly differentiated carcinoma with an inconclusive immunohistochemical profile. Further staging scans revealed pulmonary and pelvic tumor deposits. Tumor markers with alpha-fetoprotein, beta-human chorionic gonadotropin, and lactate dehydrogenase were not elevated. Follow-up cranial magnetic resonance imaging revealed intracranial disease progression and he underwent whole brain radiation therapy. Additional outside pathology consultation for chromosomal analysis revealed features consistent with a TGCT. A scrotal ultrasound revealed a minimally atrophic right testicle. With evidence supporting the potential for response to chemotherapeutic treatment in TGCT, the patient was started on cisplatin and etoposide. Bleomycin was planned for the second cycle of chemotherapy if his pulmonary function improved. A salient feature of all invasive TGCTs is a gain in material in the short arm of chromosome 12, and is diagnostic if present. Although the initial pathology revealed a non-diagnostic metastatic tumor, further testing revealed amplification of chromosome 12p. The examination of poorly differentiated carcinomas of an unknown primary site using light microscopy and immunohistochemical profiling alone may be inadequate, and should undergo molecular chromosomal analysis. This case is presented for its unconventional presentation and rarity of occurrence. It brings forward the discussion of both the commonality of TGCT in young male adults, as well as the anomaly of a 'burned out' phenomenon. With unreliable tumor markers, nonspecific symptoms, and pathological findings, 'burned out' TGCTs may account for a challenging diagnosis in a variety of cases, especially with the presenting symptom arising from a less common metastatic site. This case adds to the increasing literature on a rare entity of the 'burned out' TGCT, and upon literature review, presents itself as the first reported case presenting with brain metastasis. PMID- 27182466 TI - A Case of Purple Urine Bag Syndrome in a Spastic Partial Quadriplegic Male. AB - Purple bag urine syndrome (PUBS) is a benign and unique phenomenon of the urine turning a deep violet color within the urinary catheter tubing and bag. This phenomenon is commonly encountered in patients indicated with long-term catheter placement or, in certain conditions like chronic constipation, alkaline urine, limited ambulation, and, in terms of gender distribution, the female sex, predominates. PUBS gets its name from a unique phenomenon that takes places inside the gut where tryptophan (an amino acid) is metabolized, producing blue and red hues which together emanate a deep violet color. Here, the case of a middle-aged male patient with a suprapubic catheter in situ, following trauma causing spastic partial quadriplegia, is being presented with PUBS due to UTI secondary to Proteus vulgaris. The risk factors, in this case, include chronic constipation and recurrent urinary tract infections (UTIs).. PMID- 27182467 TI - Treatment of Nystagmus in Brainstem Cavernous Malformation with Botulinum Toxin. AB - We report a long-term eye movement study of a 68-year-old female with pontomedullary junction cavernous malformation whose dysconjugate nystagmus was treated with retrobulbar botulinum toxin A injections. Sequential, bilateral retrobulbar injections of botulinum toxin A were performed. Injections immediately decreased oscillopsia and nystagmus, and improved visual acuities. One to three months following injection, three-dimensional infrared oculography measured a significant 39-100% (P = 0.001) decrease in nystagmus amplitudes at multiple dimensions. This improvement diminished by six months in the right eye but sustained for about one year in the left eye. Over two years, botulinum toxin A injections were performed twice in the left eye and five times in the right eye. Our study supported the safe and effective use of repetitive retrobulbar botulinum toxin A injections in symptomatic nystagmus that failed medical therapy. PMID- 27182468 TI - Stereotactic Radiosurgery for Trigeminal Neuralgia: A Retrospective Multi Institutional Examination of Treatment Outcomes. AB - Objectives The purposes of this study are to assess the effectiveness of CyberKnife(r) stereotactic radiosurgery (SRS) in providing both initial and sustained pain relief for patients with both forms of trigeminal neuralgia (TN), assess potential prognostic factors, and examine treatment-related toxicities. Methods The RSSearch((r)) Patient Registry was screened for TN cases from July 2007 to June 2015. We evaluated initial pain relief achieved by examining changes in the Visual Analog Scale (VAS) scores following SRS. Prognostic factors relating to initial pain relief and the relationship between maximum dose (Dmax) and toxicity incidence were analyzed via univariate logistic regressions. We evaluated prognostic factors relating to sustained pain relief using the Kaplan Meier method and log-rank analysis. Results Our analysis included 125 TN1 patients and 38 TN2 patients with initial VAS scores >= 3 treated at 16 community radiotherapy centers. Median Dmax for both cohorts was 75 Gy with a larger range for TN1 cases (67.42 Gy - 110.29 Gy) as compared to TN2 cases (70.00 Gy - 78.48 Gy). At initial follow-up, mean VAS scores after SRS were significantly lower for TN1 and TN2 patients (p < 0.0001). The vast majority of TN1 (87.2%) and TN2 (86.8%) patients experienced initial pain relief. Higher initial VAS scores (p = 0.015) were correlated with a greater likelihood of initial treatment success for TN1 patients. We did not identify any treatment or patient characteristics that had significant effects on initial pain relief for TN2 patients. Of the TN1 cohort, 28 of 125 patients reported follow-ups one year or greater after SRS. Twenty-three of 28 TN1 patients (82%) reported VAS scores of 1 or less at one year follow-up, and eight of 11 patients (72%) had VAS scores of 1 or less at the two-year follow-up. No potential prognostic factors for long-term pain relief were significant. Roughly 18% and 11% of TN1 and TN2 patients, respectively, experienced acute toxicities (all RTOG Grade 1 or 2), with the most common being sensory neuropathy, generalized pain, and nausea. Dmax > 75 Gy was not a predictor of toxicity incidence in TN1 cases (p = 0.597) but was significant for TN2 patients (p = 0.0009 following Fisher's exact test). Conclusions SRS is an effective treatment option for TN patients in community settings. Initial pain relief following SRS was achieved in a vast majority of TN patients with associated minor toxicities observed in less than 20% of all patients. PMID- 27182470 TI - Bilateral Osteonecrosis of the Femoral Head During Pregnancy Following Two Corticosteroid Injections: A Case Report and Review of the Literature. AB - Osteonecrosis of the femoral head during pregnancy, or shortly thereafter, is a rare clinical problem. Little is known about pregnancy as an etiological factor for femoral head osteonecrosis with only 40 reported cases in the literature. Furthermore, single or dual dose steroid-induced multifocal osteonecrosis is a controversial topic with only a handful of published cases. We present a case of a 34-year-old female with bilateral femoral head osteonecrosis that developed during the peripartum period. She received two large intramuscular injections of steroids for fetal lung maturity because early delivery was required as a result of eclampsia. She underwent total arthroplasty of the left hip due to unremitting pain and functional disability, which achieved good clinical results--relieving her pain and improving her range of motion. Literature is scarce with regard to single or dual dose steroid-induced osteonecrosis of the hip as well as pregnancy as a general etiologic factor. This case highlights the need for high clinical suspicion of osteonecrosis as a cause of postpartum hip pain. PMID- 27182469 TI - A Single Institution Consensus on the Use of Sequential or Concurrent Hormonal Therapy for Breast Cancer Patients Receiving Radiation Therapy. AB - BACKGROUND AND OBJECTIVES: For hormone-sensitive breast cancers, treatment with breast-conserving surgery, tamoxifen, or aromatase inhibitors, along with adjuvant radiation, is the mainstay of therapy. The ideal timing of hormonal and radiation treatment is not well defined, and there is a significant degree of practice variability between concurrent and sequential treatment regimes. This variability can cause confusion amongst the clinical team resulting in contradictory recommendations, loss of patient trust, and the potential for missed initiation of hormonal therapy. METHODS: To address this question, a systematic review of the literature was conducted and presented to the breast cancer multidisciplinary team at the London Regional Cancer Center. A three-round modified Delphi method was used to obtain a consensus on a series of a priori determined statements. RESULTS: With the currently available evidence, the consensus was that hormonal therapy should be given sequentially after radiation. This will limit potential overlapping adverse effects between hormonal therapy and radiation that may decrease completion of treatment. The sequential approach has not been associated with any harm in clinical outcomes, and there is some suggestion of increased toxicity with concurrent use. However, in patients at high risk of distant recurrence, they felt it would be reasonable to consider concurrent treatment to avoid any delay in therapy. CONCLUSION: The consensus of our institution to utilize a sequential approach will standardize the treatment decisions and reduce the risk of failing to initiate hormonal therapy. Despite the lack of level 1 evidence, the Delphi methodology did provide a high level of confidence for our group to choose the sequential approach. The consensus was developed after a review of the literature revealed that there was no clear superiority of one schedule over the other and evidence that concurrent treatment may increase adverse events. PMID- 27182471 TI - The Effects of the 80-hour Workweek on Occupational Hazards. AB - BACKGROUND : The most recent work-hour restrictions were implemented in July 2011 for training physicians. The impact of these regulations on workplace injuries is not yet fully understood. Our goal is to determine the effect of the work-hour limitation on the rates of needlestick and eyesplash injuries. METHODS : Approximately 1200 neurosurgery residents and fellows in the United States were emailed a survey, several times, Sept 2013-February 2014. There were 212 responses across postgraduate years 1-7 and fellowship regarding the rate of needlestick and eyesplash injuries experienced or witnessed before and after July 2011. RESULTS : Regarding witnessing a needlestick/eyesplash accident: 89.33% of respondents claimed witnessing an injury. Specifically regarding percutaneous injuries (PCIs): before July 2011, 21.77% claimed never witnessing; after July 2011, only 8.9% indicated never witnessing. Specifically regarding eyesplash injuries: comparing the injuries (40.94%) before July 2011 to those (51.94%) after July 2011, the survey indicated an increase in eyesplash injuries. CONCLUSION : The results of this survey document that neurosurgery residents/fellows observed (or personally sustained) an increased number of needlestick and eyesplash injuries after implementation of the July 2011 work hour limitations. Although the last set of reduced-hour regulations have been in place for more than three years, there does not therefore seem to be a safety advantage associated with them regarding a reduction in PCI or eyesplash accidents. This may be due to other confounding factors, not yet affirmatively identified, which warrant additional investigation and identification, directed at preventing future injuries. PMID- 27182472 TI - Factors Predictive of Protracted Course of Radiation Therapy in Patients Treated with Definitive Chemoradiation for Cervical Cancer. AB - BACKGROUND: There is a benefit to completing definitive chemoradiotherapy (CRT) for cervical cancer within 56 days. However, many patients experience delays due to missed radiation treatments that prolong the overall course of therapy. In order to improve patient care, we performed a quality improvement project to determine factors predictive of protracted treatment and develop strategies to enable timely treatment completion. METHODS : Seventy-one patients treated for cervical cancer with CRT were identified. Medical records were reviewed to gather demographic, clinical, and treatment data. Prolonged treatment was defined as >56 days per the American Brachytherapy Society guidelines. The following variables were evaluated using paired t-tests and univariate logistic regression: demographics, Intensity Modulated Radiotherapy (IMRT) versus conventional radiation technique, use of a boost, time to stent placement, time to first brachytherapy (BT), and genitourinary (GU) or gastrointestinal (GI) toxicity. RESULTS: The median treatment length for all patients was 59 days. Factors associated with prolonged treatment were time to cervical stent placement (p=0.001), delay >=2 days between final external beam radiation therapy (EBRT) and initial BT (p=0.0195), any grade GU toxicity (p=0.0007), or GI toxicity (p=0.0002), and the presence of a boost (p=0.0006). Age, stage, and IMRT versus conventional technique were not associated with protracted treatment. CONCLUSION : In this series of patients, acute toxicity, increased time to cervical stent placement, and time to first BT treatment were associated with prolonged treatment time. The patients who completed treatment in <=56 days had a lower average time to cervical stent placement, 27 versus 31 days. Our results suggest that cervical stent placement during week four of treatment can enhance patient care and improve outcomes. PMID- 27182473 TI - Increasing Efficacy of Thrombectomy by Using Digital Subtraction Angiography to Confirm Stent Retriever Clot Integration. AB - Physicians performing thrombectomy for acute stroke have had increasing success as thrombectomy-specific devices have continued to evolve. As the devices evolve, so too must the techniques. The current generation of stent retriever thrombectomy devices requires five minutes of dwell time, regardless of the particularities of the case. We have noticed the presence of flow through the stent immediately prior to removal portends a lower chance of successful thrombus retrieval than when no flow is seen, regardless of dwell time. We hypothesize that interventionalists can use the presence or absence of flow to predict adequacy of seating time and decrease the number of deployments per case. This could significantly decrease time to recanalization by avoiding time-consuming, unsuccessful pulls. This is a technical report of a few cases of stent retriever thrombectomy. We propose using post-deployment digital subtraction angiography to confirm thrombus-device integration and increase the chance of thrombus removal. PMID- 27182474 TI - When Benign Tumors Mimic Malignancies: A Case of Lymphangiomatosis Masquerading as Metastatic Disease. AB - Lymphangiomatosis, a rare disorder of the lymphatic system characterized by the abnormal proliferation of lymphatic vessels, is a typically benign disorder that at times can exhibit invasive or malignant behavior. While generally considered a diagnosis of childhood, in adults the majority of cases are asymptomatic and found incidentally. Rarely, lymphatic overgrowth can occur, causing growth of lesions on imaging mimicking a metastatic process and occasionally, resulting in substantial morbidity and mortality. Here, we present such a case of lymphangiomatosis with multi-organ system involvement in liver, bone, and spleen. In addition to details of the clinical presentation and the pathologic review which led to the diagnosis, we describe our use of the tyrosine kinase inhibitor pazopanib, which may cause stabilization of lymphangiomatosis through blockade of vascular endothelial growth factor (VEGF) signaling, for systemic treatment in this unusual case. PMID- 27182475 TI - Acute Myeloid Leukemia in the Elderly Patient: New Strategies. AB - Although selected older adults with acute myeloid leukemia can benefit from intensive therapies, recent evidences support the use of lower-intensity therapies (hypomethylating agents or low-dose cytarabine) in most of these patients and emphasize the importance of tolerability and quality of life. Individualized approaches to treatment decision-making beyond consideration of chronologic age alone should therefore be considered. One promising strategy is to combine low-intensity treatments with novel agents. PMID- 27182476 TI - An Overview on the Sequential Treatment of Pancreatic Neuroendocrine Tumors (pNETs). AB - Patients suffering from pancreatic neuroendocrine tumors (pNETs) are now candidates to receive novel approved drugs that have demonstrated benefit in disease control rate and delay the time taken for tumor progression in Phase III clinical trials; for example, sunitinib, everolimus and lanreotide. Though pNETs represent a rare and heterogeneous disease, recent approaches are being taken to better understand the molecular pathways involved in carcinogenesis. Consequently, new treatment strategies are now available and others still under investigation show promising results. However, some questions around how to approach patients with pNETs are still unresolved, such as what the best sequence of treatments we can offer to each of our patients in the clinic at any time of their disease would be. Therapeutic decisions are, at the moment, guided by clinical judgment, based on different parameters coming from retrospective analysis and non-randomized clinical trials. However, advances in genomic research would lead to a more precise approach using therapeutic targets that would also allow the development of new agents, prognostic or predictive biomarkers and a better understanding of resistance mechanisms. The following article is a comprehensive review of the approved and investigational drugs in pNET, and highlights the current concerns about treatment sequencing, but also provides an update of some of the present and future efforts for an improvement in the therapeutic algorithm of the disease. PMID- 27182477 TI - Bosutinib for Chronic Myeloid Leukemia. AB - In recent years the availability of several tyrosine kinase inhibitors (TKI) in the therapeutic armamentarium for chronic myeloid leukemia has dramatically changed the objectives and expectations of healthcare providers and patients. For many, but not all, patients the forerunner of TKI, imatinib, is still an excellent treatment option. Unfortunately, nearly 30-40% of imatinib-treated patients discontinue therapy in the long-term, because of failure and/or intolerance. Second-generation tyrosine kinase inhibitors are more potent drugs which are suitable for treatment of approximately 50% of patents for whom imatinib is unsuitable, and with high success and rapid responses. Bosutinib, an orally bioavailable Src/Abl tyrosine kinase inhibitor, has proved to be effective in vitro against resistant chronic myeloid leukemia cells that do not harbor the T315I or V299L ABL kinase domain mutations. During clinical development the manageable safety profile of bosutinib have become evident for both simple and more advanced treatment. In this review we summarize preclinical and clinical data for bosutinib and discuss its ideal field of action in comparison with other TKI. PMID- 27182479 TI - Treatment of Adult Soft Tissue Sarcomas: An Overview. AB - Sarcomas are uncommon malignancies accounting for about 1% of all adult malignancies. Sarcomas are a heterogeneous group of tumors which includes more than 100 different subtypes. Surgery is the mainstay therapy for localized disease. In selected patients the combination of surgery with radiotherapy achieves better local control and offers the best chance of cure. Systemic treatment including cytotoxic chemotherapy or targeted therapies remains the mainstay therapy for most patients with advanced disease. There are a wide variety of clinical situations, such that an individualized treatment plan must be defined by a multidisciplinary tumor board. Treatment decisions should take into consideration the histology, site of disease, stage, performance status, treatment goals, and the patient's wishes. The management of patients should be carried out in a center with expertise in the treatment of sarcomas for optimal outcome. This review will cover the different treatment modalities of adult soft tissue sarcomas. PMID- 27182478 TI - Evolving Paradigms in the Management of Multiple Myeloma: Novel Agents and Targeted Therapies. AB - Multiple myeloma (MM) is a clonal plasma cell disorder defined by bone marrow infiltration and osteolytic bone lesions and is the second most common hematologic malignancy after non-Hodgkin lymphoma. The landscape of MM treatment was transformed at the dawn of the twenty-first century by the introduction of novel agents including proteasome inhibitors (bortezomib) and immunomodulatory drugs (thalidomide, lenalidomide), which have prolonged the survival of MM patients. The recently revised International Myeloma Working Group diagnostic criteria for MM added validated biomarkers (clonal bone marrow plasma cell >=60%, involved:uninvolved serum free light chain ratio >=100, or >1 focal lesion on magnetic resonance imaging) to identify near inevitable progression to symptomatic MM requiring therapy. In addition, the definition of myeloma-defining CRAB features (hypercalcemia, renal failure, anemia, and bone lesions) has been refined based on advances in imaging and laboratory techniques since the 2003 IMWG consensus. Despite expanded treatment options, MM remains an incurable disease. Drug resistance and clonal evolution remain problematic, and novel therapeutic agents are needed. New approaches to myeloma treatment include anti CD38 antibodies, next generation proteasome inhibitors, epigenetic modulation with histone deacetylase inhibitors, and targeting the tumor microenvironment. In this article, the diagnosis, staging, and prognostic stratification of newly diagnosed MM will be reviewed. Clinical data pertaining to the emerging targeted agents will be discussed, and a suggested framework for integration of these new therapeutic options will be provided. PMID- 27182480 TI - Targeted Therapy in Oropharyngeal Squamous Cell Carcinoma: The Implications of HPV for Therapy. AB - Oropharyngeal cancers caused by human papillomaviruses (HPV) have a different epidemiology, prognosis, genetic mutational landscape, response to treatment, and outcome when compared to HPV-negative cancers. In this review, a summary of our current understanding of HPV in head and neck cancer and the important advances that have shown HPV to be an etiological agent are discussed. HPV-positive and HPV-negative tumors are compared discussing clinicopathological factors, prognosis, outcome following treatment, and the molecular and genetic differences. Currently, the standard of care for oropharyngeal cancer is both surgery and post-operative radiotherapy with or without cisplatin or concurrent chemo-radiotherapy. The latter is used more often, especially in cancers of tonsil and base of tongue. However, there is increased interest in trying to de intensify treatment and in the development of new treatments to target the underlying different molecular pathways of HPV-positive cancers. The current clinical trials involving surgery, chemotherapy, and radiation therapy are discussed. The new targeted treatments are also summarized. Although there is currently is no evidence from prospective studies to support a change in the treatment algorithm, the treatment options for patients with HPV-positive disease are likely to change in the future. PMID- 27182481 TI - Molecular Monitoring as a Path to Cure Acute Promyelocytic Leukemia. AB - Acute promyelocytic leukemia (APL) is a molecularly well-defined disease, characterized by a specific chromosomal translocation; the improvement in biologic and clinical knowledge and subsequent introduction of molecularly targeted therapies have transformed the management of APL, with survival rates now exceeding 80%. Minimal residual disease (MRD) assessment in APL is the most important tool for its treatment; the prognostic role of the molecular detection of promyelocytic leukemia retinoic acid receptor alpha (PML-RARalpha) transcript after consolidation therapy in the early identification of the following hematologic relapse is now well established and guides preemptive therapy. First experiences performed with a qualitative polymerase chain reaction (PCR) approach were replaced with more accurate real-time quantitative PCR (RQ-PCR), which guarantees a numeric quantification of MRD. The identification of arsenic trioxide (ATO) as a valid therapy not only in relapsed patients but also as an alternative to standard therapy alone or in association with all-trans-retinoic acid enlarges the setting of validation of MRD evaluation in APL patients, considering a possible different clearance of PML-RARalpha with innovative therapy different from the standard ones. MRD monitoring demonstrated its validity also in the setting of relapsed patients with interesting results in the autologous and allogeneic stem cell transplantation setting or with the use of other biological agents. The aim of this review is to report and discuss the actual state of the art of MRD in APL. PMID- 27182482 TI - Reviewing Challenges in the Diagnosis and Treatment of Lentigo Maligna and Lentigo-Maligna Melanoma. AB - Lentigo maligna (LM) and lentigo-maligna melanoma (LMM) are pigmented skin lesions that may exist on a continuous clinical and pathological spectrum of melanocytic skin cancer. LM is often described as a "benign" lesion and is accepted as a melanoma in situ; LM can undergo malignant transformation to particularly aggressive melanoma. LMM is an invasive melanoma that shares properties of LM, as well as exhibiting the metastatic potential of malignant melanoma. Unfortunately, LM/LMM diagnosis based on dermoscopy is rather ambiguous, and these lesions are often mistaken for junctional dysplastic nevi over sun-damaged skin, pigmented actinic keratosis, solar lentigo, or seborrheic keratosis. Diagnosis must be made on biopsy using distinct dermatopathologic features. These include a pagetoid appearance of melanocytes, melanocyte atypia, non-uniform pigmentation/distribution of melanocytes, and increased melanocyte density in a background of extensive photodamage. Advancements in immunohistochemical staining techniques, including soluble adenylyl cyclase (antibody R21), makes diagnosis easier and allows the definition of borders down to a single cell. After a pathologic diagnosis, there are a variety of treatment options, both surgical and non-surgical. Although surgical removal with a wide excision border is the preferred treatment due to decreased recurrence rates, experimental combination therapies are gaining popularity. However, no matter the treatment, LM/LMM carries a high recurrence rate, and patients must be monitored rigorously for recurrence as well as the appearance of additional skin lesions/cancers. PMID- 27182483 TI - Scedosporium apiospermum infections and the role of combination antifungal therapy and GM-CSF: A case report and review of the literature. AB - Scedosporium apiospermum, a ubiquitous environmental mold, is increasingly reported as causing invasive fungal disease in immunocompromised hosts. It poses a therapeutic challenge due to its intrinsic resistance to traditional antifungals and ability to recur despite demonstrating susceptibility. We present an immunocompromised patient with a cutaneous S. apiospermum infection that disseminated despite treatment with voriconazole, the drug of choice. Adding echinocandins and GM-CSF provided partial recovery, indicating a potential synergistic role of dual-antifungal and immunotherapeutic agents. PMID- 27182484 TI - Subcutaneous infection by Ochroconis mirabilis in an immunocompetent patient. AB - Recently, the taxonomy of Ochroconis (Ascomycota, Pezizomycotina, Venturiales, Sympoventuriaceae) has been revised with the recognition of an additional genus, Verruconis. Ochroconis comprises mesophilic saprobes that occasionally infect vertebrates which mostly are cold-blooded, while Verruconis contains thermophilic species which is a neurotrope in humans and birds. On the basis of molecular data it is noted that only a single Ochroconis species regularly infects immunocompetent human hosts. Here we report a subcutaneous infection due to Ochroconis mirabilis in a 50-year-old immunocompetent female patient. In vitro antifungal susceptibility tests revealed that terbinafine was the most effective drug. The patient was successfully cured with oral administration of terbinafine 250 mg daily in combination with 3 times of topical ALA-photodynamic therapy for 9 months. PMID- 27182485 TI - A protracted course of Pneumocystis pneumonia in the setting of an immunosuppressed child with GMS-negative bronchoalveolar lavage. AB - We report a case of Pneumocystis pneumonia in a 5-year-old male with Trisomy 21 and acute lymphoblastic leukemia. The lack of response to trimethoprim sulfamethoxazole raised concerns for antimicrobial resistance. Further, diagnosis of Pneumocystis in this patient was complicated by a GMS-negative bronchoalveolar lavage despite molecular evidence of Pneumocystis infection. PMID- 27182486 TI - Erythroid blast crisis in chronic myelogenous leukemia: Case report and review of literature. AB - Chronic myelogenous leukemia (CML) is a myeloproliferative disorder where over a period of time 15-20% of patients show blastic transformation with majority transforming into acute myeloid leukemia, most of which are of granulocytic lineage. Erythroid blast phase of CML is relatively rare with the incidence ranging from 0-10%. Further the incidence of acute erythroid leukemia by itself is fairly low amongst all acute leukemias. We report a case of 41-year-old patient with CML who failed to achieve cytogenetic remission, transformed to acute erythroid leukemia and eventually succumbed to the disease over a short period of time. Related literature is also reviewed. PMID- 27182488 TI - White matter microstructural changes in adolescent anorexia nervosa including an exploratory longitudinal study. AB - BACKGROUND: Anorexia nervosa (AN) often begins in adolescence, however, the understanding of the underlying pathophysiology at this developmentally important age is scarce, impeding early interventions. We used diffusion tensor imaging (DTI) to investigate microstructural white matter (WM) brain changes including an experimental longitudinal follow-up. METHODS: We acquired whole brain diffusion weighted brain scans of 22 adolescent female hospitalized patients with AN at admission and nine patients longitudinally at discharge after weight rehabilitation. Patients (10-18 years) were compared to 21 typically developing controls (TD). Tract-based spatial statistics (TBSS) were applied to compare fractional anisotropy (FA) across groups and time points. Associations between average FA values of the global WM skeleton and weight as well as illness duration parameters were analyzed by multiple linear regression. RESULTS: We observed increased FA in bilateral frontal, parietal and temporal areas in AN patients at admission compared to TD. Higher FA of the global WM skeleton at admission was associated with faster weight loss prior to admission. Exploratory longitudinal analysis showed this FA increase to be partially normalized after weight rehabilitation. CONCLUSIONS: Our findings reveal a markedly different pattern of WM microstructural changes in adolescent AN compared to most previous results in adult AN. This could signify a different susceptibility and reaction to semi-starvation in the still developing brain of adolescents or a time dependent pathomechanism differing with extend of chronicity. Higher FA at admission in adolescents with AN could point to WM fibers being packed together more closely. PMID- 27182487 TI - Neural correlates of somatoform disorders from a meta-analytic perspective on neuroimaging studies. AB - Somatoform disorders (SD) are common medical disorders with prevalence rates between 3.5% and 18.4%, depending on country and medical setting. SD as outlined in the ICD-10 exhibits various biological, social, and psychological pathogenic factors. Little is known about the neural correlates of SD. The aims of this meta analysis are to identify neuronal areas that are involved in SD and consistently differ between patients and healthy controls. We conducted a systematic literature research on neuroimaging studies of SD. Ten out of 686 studies fulfilled the inclusion criteria and were analyzed using activation likelihood estimation. Five neuronal areas differ between patients with SD and healthy controls namely the premotor and supplementary motor cortexes, the middle frontal gyrus, the anterior cingulate cortex, the insula, and the posterior cingulate cortex. These areas seem to have a particular importance for the occurrence of SD. Out of the ten studies two did not contribute to any of the clusters. Our results seem to largely overlap with the circuit network model of somatosensory amplification for SD. It is conceivable that functional disorders, independent of the clinical impression, show similar neurobiological processes. While overlaps do occur it is necessary to understand single functional somatic syndromes and their aetiology for future research, terminology, and treatment guidelines. PMID- 27182490 TI - A case of pancreatitis, panniculitis and polyarthritis syndrome: Elucidating the pathophysiologic mechanisms of a rare condition. AB - Pancreatitis-Panniculitis-Polyarthritis (PPP) syndrome is rare and its physiopathology unclear. A 6-year old boy suffered of traumatic pancreatitis complicated by PPP syndrome. Extensive investigations demonstrated high levels of pancreatic lipase and fatty acids in the affected peripheral tissues. These findings support the sequence of peripheral lipolysis and fatty acid accumulation inducing tissue inflammation. PMID- 27182491 TI - Candida costochondritis associated with recent intravenous drug use. AB - Candida osteoarticular infections are being reported with increasing frequency, possibly due to an expanding population at risk. However, Candida costochondritis is uncommon. We report two cases of Candida costochondritis in patients who presented with subacute-onset chest wall swelling and whose only identifiable risk factor was a history of recent intravenous drug use. PMID- 27182489 TI - Lesion-symptom mapping of a complex figure copy task: A large-scale PCA study of the BCoS trial. AB - Complex figure copying is a commonly used neuropsychological test. Here we explored the neural basis of the factors underlying complex figure copying (CFC), using data from the Birmingham Cognitive Screen (BCoS) in a large group of sub acute, ischemic stroke patients (239). We computed two analyses: in the first we assessed the contribution of co-morbid deficits (i.e. in gesture processing, object use, visual neglect, pictures naming and sustained attention) to the lesions associated with CFC. In a second analysis a Principle Component Analysis (PCA) was used to isolate different underlying task components and to link to clinical neuroimaging scans. A voxel-based morphometry (VBM) analysis showed that poor CFC performance was associated with lesions to bi-lateral thalamus, lingual, right fusiform and right inferior parietal cortices (rIPC). The latter association with the posterior parietal cortex was diminished after controlling for neglect. Follow up analysis showed the neglect partially mediated the correlation of CFC and rIPC. The PCA revealed three main underlying components: (1) a component associated with high-level motor control common to different measures of apraxia and linked to the left postcentral gyrus, the right thalamus and middle frontal gyrus; (2) a visuo-motor transformation component unique to the CFC and associated with lesions to the posterior occipital and sensory cortices; (3) a component associated with multistep object use tasks which was correlated with lesions to the left inferior frontal orbital gyrus, the right fusiform and cerebellum. Using clinical symptoms, cognitive profiles and lesion mapping we showed that beyond visual perception, CFC performance is supported by three functional networks: one for high-level motor control, a visuo-motor transformation component, and multistep object use network. PMID- 27182494 TI - A Review of Sport-Related Head Injuries. AB - We review current topics in sport-related head injuries including acute subdural hematoma (ASDH), traumatic cerebrovascular disease, cerebral concussion, and chronic traumatic encephalopathy (CTE). Sports-related ASDH is a leading cause of death and severe morbidity in popular contact sports like American football and Japanese judo. Rotational acceleration can cause either cerebral concussion or ASDH due to rupture of a parasagittal bridging vein. Although rare, approximately 80% of patients with cerebral infarction due to sport participation are diagnosed with ischemia or infarction due to arterial dissection. Computed tomography angiography, magnetic resonance angiography, and ultrasound are useful for diagnosing arterial dissection; ultrasound is particularly useful for detecting dissection of the common and internal carotid arteries. Repeated sports head injuries increase the risks of future concussion, cerebral swelling, ASDH, and CTE. To avoid fatal consequences of CTE, it is essential to understand the criteria for safe post-concussion sports participation. Once diagnosed with a concussion, an athlete should not be allowed to return to play on the same day and should not resume sports before the concussion symptoms have completely resolved. Information about the risks and management of head injuries in different sports should be widely disseminated in educational institutions and by sport organization public relations campaigns. PMID- 27182495 TI - Symptomatic Epidural Fluid Collection Following Cranioplasty after Decompressive Craniectomy for Traumatic Brain Injury. AB - OBJECTIVE: Symptomatic epidural fluid collection (EFC) arising as a complication of cranioplasty is underestimated and poorly described. The purpose of this study was to investigate the risk factors for development of symptomatic EFC after cranioplasty following traumatic brain injury (TBI). METHODS: From January 2010 to December 2014, 82 cranioplasties following decompressive hemicraniectomy for TBI were performed by a single surgeon. Of these 82 patients, 17 were excluded from this study due to complications including postoperative hematoma, hydrocephalus, or infection. Sixty-five patients were divided into 2 groups based on whether they had developed symptomatic EFC: 13 patients required an evacuation operation due to symptomatic EFC after cranioplasty (Group I), and 52 obtained good outcome without development of symptomatic EFC (Group II). We compared the 2 groups to identify the risk factors for symptomatic EFC according to sex, age, initial diagnosis, timing of cranioplasty, cerebrospinal fluid (CSF) leakage during cranioplasty, size of bone flap, and bone material. RESULTS: A large bone flap and CSF leakage during cranioplasty were identified as the statistically significant risk factors (p<0.05) for development of symptomatic EFC. In Group I, 11 patients were treated successfully with 5 L catheter drainage, but 2 patients showed recurrent EFC, eventually necessitating bone flap removal. CONCLUSION: A larger skull defect and intraoperative CSF leakage are proposed to be the significant risk factors for development of symptomatic EFC. Careful attention to avoid CSF leakage during cranioplasty is needed to minimize the occurrence of EFC, especially in cases featuring a large cranial defect. PMID- 27182493 TI - Changes in plasma metabolites and glucose homeostasis during omega-3 polyunsaturated fatty acid supplementation in women with polycystic ovary syndrome. AB - BACKGROUND: Both fish (FO) and flaxseed oils (FLX) are n-3 polyunsaturated fatty acids (PUFA). Fish oil contains long chain while FLX contains essential n-3 PUFA. We demonstrated that FO altered insulin secretion and resistance in polycystic ovary syndrome (PCOS) women but FLX did not. Surprisingly, the effects of FO were similar to those of the n-6 PUFA-rich soybean oil (SBO). Since increased branched chain (BCAA) and aromatic amino acids (AA) affect insulin secretion and resistance, we investigated whether FO, FLX and /or SBO affect plasma metabolites, especially AA. METHODS AND FINDINGS: In this six-week, randomized, 3 parallel arm, double-blinded study, 54 women received 3.5 g/day FO, FLX or SBO. In 51 completers (17 from each arm), fasting plasma metabolites were measured at the beginning and at the end. As compared to FLX, FO and SBO increased insulin response and resistance as well as several BCAA and aromatic AA. Pathway analysis indicated that FO exerted the largest biochemical impact, affecting AA degradation and biosynthesis, amine, polyamine degradation and alanine, glycine, l-carnitine biosynthesis and TCA cycle, while FLX had minimal impact affecting only alanine biosynthesis and l-cysteine degradation. CONCLUSION: Effects of FO and SBO on plasma AA were similar and differed significantly from those of the FLX. The primary target of dietary PUFA is not known. Dietary PUFA may influence insulin secretion and resistance directly and alter plasma AA indirectly. Alternatively, as a novel concept, dietary PUFA may directly affect AA metabolism and the changes in insulin secretion and resistance may be secondary. PMID- 27182492 TI - The Correlation of Skeletal and Cardiac Muscle Dysfunction in Duchenne Muscular Dystrophy. AB - BACKGROUND: Duchenne muscular dystrophy (DMD) is characterized by progressive skeletal muscle and cardiac dysfunction. While skeletal muscle dysfunction precedes cardiomyopathy, the relationship between the progressive decline in skeletal and cardiac muscle function is unclear. This relationship is especially important given that the myocardial effects of many developing DMD therapies are largely unknown. OBJECTIVE: Our objective was to assess the relationship between progression of skeletal muscle weakness and onset of cardiac dysfunction in DMD. METHODS: A total of 77 DMD subjects treated at a single referral center were included. Demographic information, quantitative muscle testing (QMT), subjective muscle strength, cardiac function, and current and retrospective medications were collected. A Spearman rank correlation was used to evaluate for an association between subjective strength and fractional shortening. The effects of total QMT and arm QMT on fractional shortening were examined in generalized least square with and without adjustments for age, ambulatory status, and duration of corticosteroids and cardiac specific medications. RESULTS: We found a significant correlation between maintained subjective skeletal muscle arm and leg strength and maintained cardiac function as defined by fractional shortening (rho=0.47, p=0.004 and rho=0.48, p=0.003, respectively). We also found a significant association between QMT and fractional shortening among non-ambulatory DMD subjects (p=0.03), while this association was not significant in ambulatory subjects. CONCLUSIONS: Our findings allow us to conclude that in this population, there exists a significant relationship between skeletal muscle and cardiac function in non-ambulatory DMD patients. While this does not imply a causal relationship, a possible association between skeletal and cardiac muscle function suggests that researchers should carefully monitor cardiac function, even when the primary outcome measures are not cardiac in nature. PMID- 27182497 TI - Gradual Height Decrease of Augmented Vertebrae after Vertebroplasty at the Thoracolumbar Junction. AB - OBJECTIVE: Vertebroplasty is an effective treatment for vertebral compression fracture, but may progress gradual vertebral height decrease in spite of vertebroplasty. Gradual vertebral height decrease also may induce aggravation of kyphotic change without severe pain. The purpose of this study was to evaluate risk factors for gradual vertebral height decrease in the absence of recurrent severe back pain. METHODS: A retrospective analysis was performed on 44 patients who were diagnosed with a first osteoporotic compression fracture at a single level at the thoracolumbar junction. All patients were taken vertebroplasty. Possible risk factors for gradual vertebral height decrease, such as sex, age, bone mineral density, body mass index, level of compression fracture, volume of injected cement, cement leakage into disc space, and air clefts within fractured vertebrae, were analyzed. RESULTS: Gradual vertebral height decrease of augmented vertebrae occurred commonly when more than 4 cc of injected cement was used, and when air clefts within fractured vertebrae were seen on admission. In addition, the sagittal Cobb angle more commonly increased during the follow-up period in such cases. CONCLUSION: Injection of more than 4 cc of cement during vertebroplasty and air cleft within fractured vertebrae on admission induced gradual vertebral height decrease in augmented vertebrae. Thus, longer follow-up will be needed in such cases, even when patients do not complain of recurrent severe back pain. PMID- 27182496 TI - Early Decompression of Acute Subdural Hematoma for Postoperative Neurological Improvement: A Single Center Retrospective Review of 10 Years. AB - OBJECTIVE: This study was conducted to investigate survival related factors, as well as to evaluate the effects of early decompression on acute subdural hematoma (ASDH). METHODS: We retrospectively reviewed cases of decompressive craniectomy (DC) for decade. In total, 198 cases of DC involved ASDH were available for review, and 65 cases were excluded due to missing data on onset time and a delayed operation after closed observation with medical care. Finally, 133 cases of DC with ASDH were included in this study, and various factors including the time interval between trauma onset and operation were evaluated. RESULTS: In the present study, survival rate after DC in patients with ASDH was shown to be related to patient age (50 years old, p=0.012), brain compression ratio (p=0.042) and brain stem compression (p=0.020). Sex, preoperative mental status, and time interval between trauma onset and operation were not related with survival rate. Among those that survived (n=78), improvements in Glasgow Coma Scale (GCS) score of more than three points, compared to preoperative measurement, were more frequently observed among the early (less than 3 hours between trauma onset and operation) decompressed cases (p=0.013). However, improvements of more than 4 or 5 points on the GCS were not affected by early decompression. CONCLUSION: Early decompression of ASDH was not correlated with survival rate, but was related with neurological improvement (more than three points on the GCS). Accordingly, early decompression in ASDH, if indicated, may be of particular benefit. PMID- 27182498 TI - Craniotomy or Decompressive Craniectomy for Acute Subdural Hematomas: Surgical Selection and Clinical Outcome. AB - OBJECTIVE: Craniotomy (CO) and decompressive craniectomy (DC) are two main surgical options for acute subdural hematomas (ASDH). However, optimal selection of surgical modality is unclear and decision may vary with surgeon's experience. To clarify this point, we analyzed preoperative findings and surgical outcome of patients with ASDH treated with CO or DC. METHODS: From January 2010 to December 2014, data for 46 patients with ASDH who underwent CO or DC were retrospectively reviewed. The demographic, clinical, imaging and clinical outcomes were analyzed and statistically compared. RESULTS: Twenty (43%) patients underwent CO and 26 (57%) patients received DC. In DC group, preoperative Glascow Coma Scale was lower (p=0.034), and more patient had non-reactive pupil (p=0.004). Computed tomography findings of DC group showed more frequent subarachnoid hemorrhage (p=0.003). Six month modified Rankin Scale showed favorable outcome in 60% of CO group and 23% of DC group (p=0.004). DC was done in patient with more unfavorable preoperative features (p=0.017). Patients with few unfavorable preoperative features (<6) had good outcome with CO (p<0.001). CONCLUSION: In selective cases of few unfavorable clinical findings, CO may also be an effective surgical option for ASDH. Although DC remains to be standard of surgical modality for patients with poor clinical status, CO can be an alternative considering the possible complications of DC. PMID- 27182499 TI - Early Experience of Automated Intraventricular Type Intracranial Pressure Monitoring (LiquoGuard(r)) for Severe Traumatic Brain Injury Patients. AB - OBJECTIVE: The LiquoGuard(r) system is a new ventricular-type monitoring device that facilitates intracranial pressure (ICP)-controlled or volume-controlled drainage of cerebrospinal fluid (CSF). The purpose of this study is to report the authors' experience with the LiquoGuard(r) ICP monitoring system, as well as the clinical safety, usefulness, and limitations of this device in the management of patients with traumatic brain injury (TBI). METHODS: Intraventricular ICP monitoring was performed on 10 patients with TBI using the LiquoGuard(r) monitoring system. ICP measurements, volume of drained CSF, and clinical outcomes were analyzed and discussed. RESULTS: ICP monitoring was performed on 10 patients for a mean duration of 6.9 days. With a mean 82,718 records per patient, the mean initial ICP was 16.4 mm Hg and the average ICP across the total duration of monitoring was 15.5 mm Hg. The mean volume of drained CSF was 29.2 cc/day, with no CSF drained in 4 patients. Seven of 10 patients showed 1 or 2 episodes of abnormal ICP measurements. No patient exhibited complications associated with ICP monitoring. CONCLUSION: The LiquoGuard(r) system is a versatile tool in the management of TBI patients. Its use is both reliable and feasible for ICP monitoring and therapeutic drainage of CSF. However, episodes of abnormal ICP measurements were frequently observed in patients with slit ventricles, and further study may be needed to overcome this issue. PMID- 27182500 TI - Multiple Cerebral Infarctions due to Unilateral Traumatic Vertebral Artery Dissection after Cervical Fractures. AB - We report a case of multiple symptomatic cerebral infarctions from a traumatic vertebral artery dissection (VAD) after cervical fractures. A 73-year-old man was admitted with stuporous mentality and left hemiparesis after a motor-vehicle accident. A brain computed tomography (CT) scan at admission showed a traumatic subarachnoid hemorrhage on the left parietal lobe. A cervical CT scan showed left lateral mass fractures on C2, C5, and C6, involving the transverse foramen. Cervical spine magnetic resonance imaging (MRI) revealed loss of signal void on the left vertebral artery. Neck CT angiography showed left VAD starting at the C5 level. Brain MRI revealed acute, multiple cerebral infarctions involving the pons, midbrain, thalamus, corpus callosum, and parietal and frontal lobes on diffusion weighted images. The patient was treated conservatively at the intensive care unit in the acute stage to prevent extent of stroke. Aspirin was started for antiplatelet therapy in the chronic stage. The possibility of symptomatic cerebral infarctions due to traumatic VAD following cervical fracture should be considered. PMID- 27182503 TI - FAREWELL, PROFESSOR VICTOR ANOMAH NGU (19(th) February 1926 - 14(th) June 2011). PMID- 27182502 TI - MISCONCEPTIONS, MISCONSTRUCTIONS AND MISCONNECTIONS: THE VISAGE AND FATE OF MIDDLE LEVEL SURGICAL MANPOWER IN WEST AFRICA. PMID- 27182501 TI - DONOR SITE MORBIDITY FOLLOWING HARVEST OF SPLIT-THICKNESS SKIN GRAFTS IN SOUTH EASTERN NIGERIA. AB - BACKGROUND: Split-thickness skin grafting is a very common procedure. Few documentation of its complications exist in the literatures especially in our sub region where excessive scarring is a major issue. OBJECTIVE: The objective of the study was to document the common complications observed at the donor site for split thickness skin grafts. METHODS: This is a prospective study carried out at the National Orthopaedic Hospital, Enugu, Nigeria over a six month period. All patients with wounds requiring split-thickness skin grafts, who gave consent, were recruited. An observer administered questionnaire was opened for each patient. Any donor site complication was noted on inspection and documented. Analysis of the results was done using SPSS with frequencies, mean and test of significance. RESULTS: A total of 120 patients were recruited for the study. Males accounted for 59.2% of the patients while females made up 40.8%. Donor site complications noted were pain which was exaggerated after 24 hours, itching, infection, dyschromia, hypo-pigmentation, hyper-pigmentation, and hypertrophic scars. At 1 month post-operative period, dyschromia was the commonest complication (39.2%), followed by itching (22.5%), hypo-pigmentation (19.2%), infection (17.5%), and exaggerated pain (1.7%). However, by 3 months, hyper pigmentation was most common (55.4%), followed by dyschromia (37.5%), hypertrophic scar (3.6%) and itching (3.6%). Whereas by 6 months most patients had hyper-pigmentation (96.0%) while 4.0% had hypertrophic scars. The exaggerated pain was treated successfully with analgesics and was no longer present in any patient after the first month. While infection was also treated successfully following wound swab culture and sensitivity, appropriate antibiotic therapy and local wound care. Pigmentation changes were in keeping with previous studies as hyper-pigmentation was an invariable event following healing of a partial thickness wound. CONCLUSION: Donor site morbidity can be a big problem especially with regard to infection which increases duration of admission and therefore cost of management. PMID- 27182504 TI - THESIS/DISSERTATION AS A PART OF SURGERY FELLOWSHIP EXAMINATION: IS THIS NECESSARY? PMID- 27182505 TI - The Intersection of Research and Surgical Training. PMID- 27182506 TI - CARDIOPULMONARY RESUSCITATION - KNOWLEDGE, ATTITUDE & PRACTICES IN OSUN STATE, NIGERIA. AB - BACKGROUND: Cardiopulmonary arrest is not an uncommon event in the medical practice with the causes ranging from reversible to irreversible causes. Therefore the skill in the performance of effective cardiopulmonary resuscitation is an essential part of successful medical practice. In some developed countries the CPR Training programmes were mandatory for all health care givers and even for non medical workers. However in the setting of ours, the situation is not so as most heath workers go for CPR Training programmes by wish except in some few centres were it is mandatory. AIM & OBJECTIVES: To assess the knowledge, attitudes and practices of medical practitioners in relation to cardiopulmonary resuscitation and defibrillation. SETTING: The study was carried out among medical practitioners in Osun State, Southwest Nigeria. METHODS: The study was conducted through a survey of medical practitioners in Osun state during an annual general meeting using a self administered questionnaire. RESULTS: The response rate was 65% with 65 out of 100 physicians returning the completed questionnaire. Only 40% of respondents had attended a basic and an advanced life support training programme while 30% knew how to operate an automated external defribellator (AED), seventy percent knew the meaning of AED. Most of the respondents that had attended a basic and an advanced life support programme were residents (80%) while 16% were consultants and the remaining 4% were general practitioners. More males (67%) among the respondents that knew how to operate an AED and majority (56%) were in the age range of 30-40years. Eighty two percent of the respondents would prefer to do a chest compression only resuscitation of which 44% were. CONCLUSION: Most of the medical practitioners in Osun State were not knowledgeable about cardiopulmonary resuscitation and defibrillation . The few with the knowledge were from the tertiary institutions. There is therefore the need for the creation of more awareness among medical practitioners, especially among those outside tertiary health facilities. PMID- 27182507 TI - Accreditation of Training Programmes by the West African College of Surgeons. AB - The establishment of surgical training programmes of the West African College of Surgeons started in six teaching hospitals the early 1970s in Nigeria and Ghana; it was championed by College Fellows, surgeons who had returned to the sub-region after having trained in Europe and America. Surgical programmes accreditation, captured in the College's constitution and mission statement, uses objective guidelines in the identification and encouragement of suitable institutions for surgical training through periodic peer-review audits of installed manpower, facilities, clinical services and academic programmes. This pan-regional model adopted by the five Anglophone countries of West Africa has standardized and nurtured surgical training in the disciplines of surgery, obstetrics and gynaecology, ophthalmology, otorhinolaryngology, dental surgery, radiology and anaesthesia. It has also proven to be a useful template in the current drive for the ongoing harmonization of surgical training programmes with Francophone West African as a prelude to an integrated sub-regional accreditation body. This paper details the evolution of surgical programmes accreditation in West Africa, its progress, challenges, opportunities and future trends. PMID- 27182508 TI - FACTORS DETERMINING THE RESULTS OF THE EXAMINATION OF THE WEST AFRICAN COLLEGE OF SURGEONS IN GENERAL SURGERY. AB - BACKGROUND: The general surgery results of the West African College of Surgeons (WACS) post-graduate fellowship examination could not be regarded as satisfactory when compared with the results of similar post-graduate examinations in some developed countries. For example the pass rate of the West African College of Surgeons examination was usually under 40% whereas the pass rate in oral examination in a similar post-graduate examination, the American Board of Surgery was 84% in 2006, 73% in 2012. The first time pass rate in general surgery of final year general surgery residents at the American Board of Surgery qualifying and certifying examinations were 74% - 78% between 2000 and 2007. AIM & OBJECTIVES: To identify the factors responsible for the high failure rate at the general surgery fellowship examinations of the West African College of Surgeons. STUDY DESIGN: Descriptive study .We studied and analyzed the West African College of Surgeons examination results for April 2012, October 2012, April 2013 and October 2013 with emphasis on the results, the conduct of the examination and the opinion from fellows about the examiners. Well structured questionnaires were sent to fellows who had passed all the various fellowship examinations of the West African College of Surgeons in general surgery to indicate their opinion about the examination, and the examiners. SETTING: University College Hospital, Ibadan, and Jos University Teaching Hospital, Jos, Nigeria. METHODOLOGY: The first part of the study dealt with an analysis of each section of the examination prospectively studied over a 2-year period. This consisted of four sets of examination results. The second part was a questionnaire-based study administered to Fellows who had passed the WACS final fellowship examination in general surgery. The questionnaire had three sections: primary, part 1 and part 2 and included basic demographics, date at attempts in each grade of the examinations and the outcome. It also included the views of the respondents on the conduct of the examination and outcome. The data were analyzed using Microsoft Excel. RESULTS: A total of 720 candidates with age range of 28 - 39 years and a mean of 33.2 years sat for the Part 1 Fellowship examinations in 2012 and 2013 with an average of 180 candidate per examination. At the Part 2 fellowship examination, 84 candidates with the age range of 31 - 42 year and a mean of 36.5 years sat the Part 2 Fellowship examination with an average of 21 candidates for each Part 2 examination in general surgery during the same period. The examinations held in April and October of each year. While an average of 28.8% of the candidates passed, an average of 71.2% of the candidates failed the Part 1 Fellowship examinations in 2012 and 2013. The aggregate clinical score was responsible for failure in 59.5% of the candidates. In the Part 2 Fellowship examination in general surgery during the same period, 31.5% of the candidates passed while an average of 68.5% of the candidates failed per examination. The aggregate clinical score was responsible for 53.3% of the candidates who failed the Part 2 examination. Furthermore, 60 - 69.7% of the candidates had a favourable opinion about the conduct of the examination, 54.5 - 63.6% rated the professionalism of the examiners high, even though the pass rate at the first attempts of the various grades of the examination by the respondents was about 50 percent. CONCLUSION: The clinical part of the examination is a major factor responsible for the high failure rate in the general surgery fellowship examinations of the West African College of Surgeons. In order to mitigate this, residents in training should be exposed to the clinical management of a wide range of cases in the discipline with majority of the operations performed by them under the direct supervision of their consultants. PMID- 27182509 TI - SPECTRUM OF SPINAL ABNORMALITIES ON MAGNETIC RESONANCE IMAGING OF PATIENTS WITH CLINICAL SUSPICION OF SPINAL LESIONS IN KANO, NIGERIA. AB - BACKGROUND: Magnetic resonance imaging (MRI) of the spine is a powerful tool for evaluation, assessment of severity, and follow up of diseases of the spine. It is one of the most sensitive diagnostic tests for detecting anatomic abnormalities of the spine and the adjacent structures. AIM: To determine the pattern of spinal abnormalities on MRI in Kano, Nigeria. MATERIALS AND METHOD: Patients aged between 2 and 95 years who had spinal MRI with AIRIS II TOSHIBA (0.5T) Tesla machine from January to December 2013 were reviewed. Information concerning age, gender, region and findings were recorded. RESULTS: Two hundred and sixty one patients made up of187 males and 74 females were reviewed. Their ages ranged from 2 to 95 years with the mean of 46.43 +/- 15.7 years. Lumbo-sacral MRI was the most commonly performed (46.4 %) followed by cervical (44.1%), thoraco-lumbar spine (4.2%), thoracic spine (3.8%) and cervical and lumbar (1.5%). The most common indication of MRI was low back pain in 211 (80.8% ) patients followed by trauma in 36 (17.8% ) patients. About 19.6% of the MRI examinations were normal while spondylosis and moderate disc prolapse was seen in 31.5% and compressive fracture comprised 7.3% of cases. CONCLUSION: Lumbo-sacral MRI was the commonest MRI in this study and the commonest indications for MRI were low back pain and trauma while the commonest findings were spondylosis, disc prolapse, compressive fracture and spinal metastases. PMID- 27182510 TI - TREATMENT OF BREAST CANCER: IMO STATE NIGERIA VERSUS INDIANA, USA WOMEN - COMPARATIVE ANALYTIC STUDY. AB - BACKGROUND: Women with breast cancer undergo multimodal treatment for best outcome. This study seeks to identify the treatment challenges for such women in Imo State, Nigeria vis-a-vis similar women in Indiana USA. We compared the treatment modalities of both groups; noting predictors of compliance for subsequent action. SETTING: Federal Medical Centre, Owerri; Imo State, Imo State University, Orlu, Nigeria and Indiana University Hospital, Indiana, USA. DESIGN: A retrospective study. METHODOLOGY: From 2000-2013, 100 randomly pulled charts of patients treated for pathologically confirmed breast cancer in Imo, Nigeria Federal Medical Centre Owerri, Imo State University Hospital; and Indiana University Hospital U.S. respectively were reviewed. The demographics, clinical and pathological data of the patients with confirmed breast cancer were obtained. The data were formatted and analyzed with SPSS version 16.0. The clinical features, management options, outcomes and specific features were compared for both groups using Wilcoxon Rank Sum tests (age, parity) and chi-square tests for all other variables. A 5% significance level was used for all tests. RESULTS: One hundred patients were included for each group. The mean/minimum ages; Imo, Nigeria 41.7/21 (SD/SE 15.3/1.5) vs. Indiana, U.S.56.4/29 (SD 12.4/SE 1.2) p<0.0001. Histology for Indiana USA women was predominantly ductal carcinoma in situ (DCIS) P<0.0001 while that of Imo, Nigeria was invasive ductal carcinoma inflammatory cancer P<0.0326. Women in both locations received chemotherapy and surgery. Imo women received less radiotherapy. Toxicity from chemotherapy remained constant features for both groups, P<0.0001. In Indiana USA, the 5year survival exceeded 85%; In Imo Nigeria it was 10%. This study showed that Women on both locations who were likely to be compliant were those receiving mastectomy; Imo, Nigeria 44(56%) <0.013 vs. Indiana, U.S. 74(80%) p<0.0186; women with cosmesis given; Imo, Nigeria 41(42%) vs. Indiana, U.S. 91 (94%) p<0.0001. Sample sizes were inadequate to perform multivariable models. CONCLUSION: The multimodal treatment regimen implied that there was need for an algorithm protocol for breast cancer women. Thus the need to improve the quality of treatment particularly in Nigeria by improved treatment documentation to overcome key barriers involving information exchange. PMID- 27182511 TI - CLINICO-PATHOLOGICAL FEATURES OF PROSTATE CANCER AT THE UNIVERSITY HOSPITAL YALGADO OUEDRAOGO, OUAGADOUGOU, BURKINA FASO. AB - BACKGROUND: Prostate cancer is not uncommon in Burkina Faso and presents late, often advanced at presentation as is the case in most countries of West Africa. AIM: To describe the clinical and histopathological characteristics of prostate cancer at the University Hospital Yalgado Ouedraogo, Burkina Faso. PATIENTS & METHODS: We conducted a cross-sectional descriptive study of patients treated at the Urology Department of the University Hospital Yalgado Ouedraogo, Burkina Faso for prostate cancer from March 2012 to May 2013. The parameters studied were patients' demographics, clinical features, PSA, histological diagnosis, tumour grading, management and outcome. RESULTS: In this study, 82 patients satisfied the inclusion criteria within the 15 months period of the study. The mean age was 68.9 years (standard deviation: 9.52) with a range of 49-95 years. They presented with symptoms of lower urinary tract obstruction in 57 (69.5%) patients, and irritative symptoms in 59 (72%) patients. At diagnosis 33 (40.2%) of patients had metastases and the most common metastatic sites were the spine in 18(21. 95%), the ribs in 6 (7.31%) and the pelvis in 5 (6.09%) patients. The mean PSA level was 746 ng/ml with a range of 13 - 9224ng /ml. Advanced T3 and T4 tumors accounted for 25.4% and 73.2% respectively. Adenocarcinoma was the only histological form. Gleason score was less than 7 in 41(49.4 %) cases. Androgen deprivation therapy (ADT) was the treatment for 79 (96.34%) patients. In all, 51 (62.19%) patients received medical ADT while 20 (24.39%) patients underwent bilateral orchiectomy. One patient underwent radical prostatectomy. CONCLUSION: In this environment, prostate cancer is diagnosed at an advanced stage with distant metastasis. It is therefore useful to develop effective screening policy for early detection and better outcome of management. PMID- 27182512 TI - THE STANDARD OF PLAYGROUNDS AND SAFETY MEASURES IN PREVENTION OF TRAUMATIC DENTAL INJURIES IN NIGERIAN PRIMARY SCHOOLS. AB - BACKGROUND: Playgrounds provide a recreational refuge for children and play a role in the development of their cognitive, psychosocial, and physical coordination skills. Unfortunately, it may also be a source of traumatic dental injuries (TDI). AIM: To assess the standards of playgrounds in primary schools in Southern Nigeria. SETTING: Selected public and private primary schools in Lagos (Southwest), Enugu (Southeast) and Rivers (Southsouth) states of Nigeria. MATERIALS & METHODS: Multi-stage sampling was used to select 180 schools (30 private and 30 public schools in each state) spread across the 3 study states of Lagos, Enugu and Rivers of Nigeria. A structured questionnaire which was interview administered was used to obtain information from the head teachers of 180 selected schools in Southern geo-political zones of Nigeria. The presence or absence of playgrounds & play equipment; quality of playgrounds and equipment; and supervision of the pupils during play were assessed. Statistical comparison of public and private schools, as well as comparison between the three geopolitical zones was by chi square statistics and one way ANOVA respectively. RESULTS: Playgrounds were present in 147(81.7%) schools; 83 (56.5%) and 64 (43.5%) were public and private schools respectively. Ninety three (51.7%) schools had teachers or minders at the play grounds during recreation. Most of the public schools had no minders. Majority (69.7%) of the playgrounds surfaces were bare earth. Ninety three (55.4%) schools had play equipment with about 7.5% of them padded. The maintenance of the play equipment was not regular in 54.3% of the schools. The impact absorbing surfaces under the play equipment were majorly (66.6%) pits filled with sand in the three zones while rubber matting was found only in 7.7% of schools which were exclusively in the Southwestern zone of the country. CONCLUSION: Most of the schools had playgrounds but inadequate consideration was given to safety measures in terms of playground size, surfaces, equipment type, height and supervisions by teachers. We therefore recommended that playgrounds should be standardized in Nigerian primary schools and more awareness about the occurrence and prevention of TDI during recreation should be created in schools. PMID- 27182513 TI - EXPERIENCE WITH MANAGING SOLID KIDNEY TUMOURS IN COTONOU, BENIN REPUBLIC. AB - BACKGROUND: Kidney cancer is the third most common urological tumour. Diagnosis is made in most cases at an advanced stage of the disease in our setting. AIM & OBJECTIVES: The aim of this work was to describe the management of solid tumors of the kidney and the outcome at the National University Hospital, Cotonou, Benin Republic, from January 2008 to December 2014. PATIENTS & METHODS: This is a retrospective, descriptive study conducted at the Clinic of Urology and Andrology at the National University Hospital CNHU-Hubert Koutoukou MAGA in Cotonou, Benin Republic. We included patients managed for solid kidney tumours from January 2008 to December 2014. The demographics, clinical presentations, management and outcome were recorded and the data obtained were analyzed using Epi info 3.2.2. RESULTS: Hospital frequency of solid renal mass was 1.9% with a mean age of 54 years and sex ratio of men to women of 1.6. Hematuria, back pain and lumbar mass were the most frequent clinical presentation found in 79.5% of cases. In all, 5% presented at an early stage while 95% presented at a late stage. Diagnosis was based on imaging; histopathological examination was requested in all the case though some could not afford the cost. Radical nephrectomy was performed in 51.5% of cases.The non- operated cases were those whose poor general condition as well as those who could not afford the procedure. Undifferentiated adenocarcinoma was the predominant pathological type found in 78% of operated cases. No patients underwent other treatments such as radiation therapy, immunotherapy or chemotherapy. Mortality occured in 10 cases including 1 intra operative death, 3 patients died in the early post operative period due to respiratory distress and 7 patients died from metatstasis discovered post operatively. CONCLUSION: This study has shown that majority of patients with solid renal tumours in this environment present late with advanced stages of the disease. The absence of the necessary investigative equipment, poverty and absence of adjuvant and adjunct therapeutic facilities make the treatment outcome poor. PMID- 27182514 TI - PATTERN OF OROFACIAL BACTERIAL INFECTIONS IN A TERTIARY HOSPITAL IN SOUTHWEST, NIGERIA. AB - BACKGROUND: Orofacial bacterial infections present in diverse patterns due to the anatomical complexity of the area. The likelihood of spread from the initial area of infection is also high because of the presence of contiguous spaces in the head and neck region. AIM: To determine the pattern and management outcome of orofacial bacterial infections in Southwest Nigeria. STUDY DESIGN: A prospective study. SETTING: University College Hospital, Ibadan, Nigeria. MATERIALS AND METHODS: A prospective study on 102 patients with orofacial bacterial infections seen between June and December, 2011 was carried out. The information collected with data sheet included socio- demographic data, clinical history and examination, treatment and outcome. Frequencies, means, medians and diagrams of relevant variable generated. Chi square test was used to test association between categorical variables at p<0.05. RESULTS: Male to female ratio was 1.1: 1 with age range 10 months to 83 years and mean age 33.0 (+/-20.3) years. The median number of days between onset of orofacial bacterial infection and presentation for treatment was 7 (range 3-90) days. Sixty seven (65.7%) patients presented to hospital within 7 days of the onset of symptoms of infection. Pain was the common symptom 100 (98.04%), followed by sleep disturbance 71 (69.6%) while the least common symptom was dyspnea 18 (17.7%). Most of the early presenters had complaint of sleep disturbance (67.6%) while most of the late presenters had dyspnea (44.4%). Positive medical history including diabetes mellitus was reported by 28 patients (27.6%). Sixty seven (65.7%) had fascial space involvement, of which the majority 38 (56.7%) had multiple space involvement. Eight (21%) of those with multiple space involvement had submental, bilateral sublingual and submandibular spaces (Ludwig's angina).The majority 12 (41.4%) of those with single space infection had it in submandibular space. The majority 35 (45%) of the patients with odontogenic infections had it in right posterior mandible. All the patients had antibiotics prescribed for them and also had one form of surgical treatment or the other which included extraction, incision and draina cge with extraction, decompression, exploration and debridement and sequestrectomy. The majority (90.5%) of the participants whose orofacial bacterial infection resulted into swelling had regression of the swelling and majority (90.0%) of those who had inadequate mouth opening had adequate mouth opening after treatment. Three mortalities were recorded in the course of the study. CONCLUSION: Odontogenic aetiology is commoner than non odontogenic. Multiple fascial space involvement occurred more than single space. Outcome was good with adequate treatment although few cases of mortalities were recorded. PMID- 27182515 TI - PERCEPTION OF EPIDURAL ANALGESIA FOR LABOUR AMONG PREGNANT WOMEN IN A NIGERIAN TERTIARY HOSPITAL SETTING. AB - BACKGROUND: Epidural anaesthesia is the preferred technique and gold standard for labour analgesia. However this technique is poorly utilized in our setting .This study is therefore aimed to assess the perception of this technique for labour analgesia among pregnant women in a Nigerian tertiary hospital setting in order to suggest ways of improving the utilization of same. AIM & OBJECTIVES: To assess the knowledge and percerption of women regarding epidural analgesia for labour in the antenatal clinics. SETTING: University of Benin Teaching Hospital, Benin, Southsouth Nigeria. METHODS: A total of 420 women attending the antenatal clinics of the University of Benin Teaching Hospital in South-south Nigeria were interviewed using semi-structured researcher-administered questionnaires. Respondents' socio-demographic characteristics, knowledge of epidural analgesia and its acceptance were obtained, documented and analyzed. RESULTS: Four hundred and five (94.6%) out of 420 gave complete responses to the questions asked. A majority of the respondents 322(79.5%) were not aware of epidural analgesia. Of the 83(20.9%) who were aware, 22.9% knew it was used to relieve labour pain and 20(24.1%) had first knowledge about epidural analgesia from health workers. A majority of the respondents 310(76.5%) would accept epidural analgesia if offered to them. The level of education and previous labour experiences were statistically significantly associated with awareness and acceptance of epidural analgesia respectively (p = 0.000). CONCLUSION: This study has shown that there is poor awareness and acceptance of epidural analgesia in labour in this environment which would be greatly improved by public enlightenment and counselling during ante-natal visits. PMID- 27182516 TI - WEST AFRICAN COLLEGE OF SURGEONS FELLOWSHIP EXAMINATIONS. PMID- 27182517 TI - MODE OF TRANSMISSION OF HIV/AIDS: PERCEPTION OF DENTAL PATIENTS IN A NIGERIAN TEACHING HOSPITAL. AB - BACKGROUND: Despite the fact that the possible modes of transmission of Human Immunodeficiency Virus (HIV) are well established, there still abound many misconceptions, which contribute to the persistence of social stigmatization of those living with the virus. AIM: To assess the perception of some dental patients on the possible modes of transmission of HIV in order to identify areas of misconceptions. DESIGN OF THE STUDY: A prospective study. SETTING: A dental centre located within a teaching hospital in Nigeria. MATERIALS & METHODS: A prospective study of 212 dental patients was undertaken using a structured questionnaire to assess the perception of respondents on possible mode of transmission of HIV. RESULTS: Majority of the respondents agreed that HIV could be transmitted through sexual means (96.2%), blood transfusion (96.7%) and sharing of sharp objects (92.5%). A few of the respondents believed that HIV can be transmitted through sharing of drinking cups (9.4%) and mosquito bites (13.6%). A greater percentage of those with higher educational qualifications agreed that the use of unsterilized dental instruments may transmit the virus, which was statistically significant (p< .002) and a lower percentage of the more educated respondents agreed that sharing of drinking cup can transmit the virus (p<.000). CONCLUSION: Despite the generally good knowledge of the possible modes of transmission of HIV, there are still some misconceptions, which may encourage stigmatization of those living with HIV, which could lead to people unwilling to consent and go for voluntary counseling and testing. PMID- 27182518 TI - THE PATTERN OF DENTAL CARIES IN CHILDREN IN PORT HARCOURT, NIGERIA. AB - BACK GROUND: Dental caries is a preventable oral disease in children and its prevention can only be effective when the pattern is known. There is paucity of this information in South - South Nigeria. AIM & OBJECTIVES: To describe the pattern of dental caries in Nigerian children in Port Harcourt, Rivers State, Nigeria. DESIGN OF THE STUDY: A Retrospective study. SETTING: Paediatric Dental clinic, University of Port Harcourt Teaching Hospital, Port Harcourt, Rivers State, Nigeria. MATERIALS AND METHODS: The dental records of 334 patients that attended the dental clinic in 2013 were reviewed for the following information: socio demography, oral hygiene practices, dietary habits and presence and pattern of dental caries. RESULTS: One hundred and forty two (42.5%) children had dental caries during the study period. They consisted of 65 (45.8%) males and 77 (54.2%) females with a mean age of 9.14 (+ 3.94) years and a range of 1to16years. Majority (78.5%) cleaned their teeth once a day and 83.3% of the children below seven years of age cleaned their teeth by themselves. All the children ingested refined carbohydrates in varying frequencies. The 5 to 9 year age cohort was 43% of those who had dental caries. Most of the carious lesions were located on the occlusal surfaces (61.2%) while the least sites (1.2%) were the lingual surfaces in both dentitions. The carious lesions were more in the posterior teeth of the lower jaw. There were no anterior teeth affected in the permanent dentition. There was an association between the age and the severity of caries (p<0.05). CONCLUSION: The occlusal surface was the commonest occurrence site of the dental caries, therefore the children at risk of developing caries will benefit more from dental sealants placement. PMID- 27182519 TI - ASSESSMENT OF OXIDATIVE STRESS IN EARLY AND LATE ONSET PRE-ECLAMPSIA AMONG GHANAIAN WOMEN. AB - BACKGROUND: Pre-eclampsia is a multisystem pregnancy-related disorder with multiple theories regarding its aetiology resulting in lack of reliable screening tests and well-established measures for primary prevention. However, oxidative stress is increasingly being implicated in the pathogenesi of pre-eclampsia although conflicting findings have been reported. AIM: To determine and compare the levels of oxidative stress in early and late onset pre-eclampsia by measuring urinary excretion of isoprostane and total antioxidant power (TAP) in a cohort of pre-eclamptic women at Korle Bu Teaching Hospital. METHODOLOGY: This was a cross sectional study conducted at Korle-Bu Teaching Hospital, Accra, Ghana involving pre-eclamptic women between the ages 18 and 45 years who gave written informed consent. Urinary isoprostane levels were determined using an enzyme-linked immunosorbent assay (ELISA) kit whereas the Total Anti-oxidant Power in urine samples was determined using Total Antioxidant Power Colorimetric Microplate Assay kit. The data obtained were analyzed using MEGASTAT statistical software package. RESULTS: We included 102 pre-eclamptic women comprising 68 (66.7%) and 34 (33.3%) with early-onset and late-onset pre-eclampsia respectively. There were no statistically significant differences between the mean maternal age, haematological indices, serum ALT, AST, ALT, albumin, urea, creatinine uric acid and total protein at the time of diagnosis. The mean gestational age at diagnosis of early and late onset pre-eclampsia were 31.65 +/- 0.41 and 38.03 +/- 0.21 respectively (p ? 0.001). Also, there were statistically significant differences between the diastolic blood pressure (BP), systolic BP and mean arterial pressure (MAP) at diagnosis of pre-eclampsia in the two categories. The mean urinary Isoprostane excretion was significantly higher in the early onset pre-eclamptic group (3.04 +/- 0.34 ng/mg Cr) compared to that of the late onset pre-eclamptic group (2.36 +/- 0.45 ng/mg Cr), (p=0.019). Urinary total antioxidant power (TAP) in early onset PE (1.64 +/- 0.06) was lower but not significantly different from that of late onset PE (1.74 +/- 0.09) with p = 0.369. CONCLUSION: Significantly increased urinary isoprostane excretion was detected in early onset pre-eclampsia compared to late onset pre-eclampsia, suggestive of increased oxidative stress in the former. However, there was no significant difference in total anti-oxidant power between the two categories of pre-eclampsia women although there was a tendency of reduced total antioxidant power in the women with early onset pre ecalmpsia. PMID- 27182520 TI - PERIODONTAL SYSTEMIC INTERACTION: PERCEPTION, ATTITUDES AND PRACTICES AMONG MEDICAL DOCTORS IN NIGERIA. AB - BACKGROUND: Periodontal diseases (PD) impact the outcome of some systemic illnesses. Medical doctors' knowledge and practices regarding this association may influence the effective management of their patients. This has been understudied among Nigerian doctors. AIM: The study aimed to determine the knowledge, attitudes and practices regarding periodontal-systemic disease interactions among medical doctors in Nigeria. METHODOLOGY: This was a descriptive, cross sectional study by design, while the study setting was at the National Postgraduate Medical College of Nigeria (NPMCN), Ijanikin, Lagos. The study participants were senior resident doctors attending compulsory Research Methodology and Management courses organized by the NPMCN in 2014. Self administered questionnaires were distributed among the participants to obtain information on their socio-demography, PD knowledge, association between PD and systemic illnesses, attitudes to periodontal health and oral hygiene practices questionnaires. Student t test and ANOVA were used to test associations between variables. The level of significance was set at p < 0.05. RESULTS: A total of 236 doctors participated in the study with a mean age of 35.8 (+/- 4.5) years, males being predominant (62.7%). Few doctors (42.1%) knew dental plaque as the main cause of PD, while 16.5% were aware of gum bleeding as earliest sign. Female doctors displayed better knowledge than males (p= 0.044). Majority were aware of an association between PD and chronic kidney disease (88.6%) and diabetes (86.5%). Knowledge of PD as a risk factor for stroke was 33.1%, poor glycemic control (25.4%), and pre-term low birthweight (14.8%). Most doctors had positive attitudes towards patients' periodontal health, while 33.5% assessed their patients' oral cavity regularly. All the doctors used tooth brush and paste to clean their teeth, while 43.2% cleaned twice daily. Only 16.5% used dental floss frequently and was associated with higher PD knowledge (p<0.001) and higher attitude scores (p=0.005). CONCLUSION: Senior resident doctors in Nigeria have positive attitudes regarding periodontal health. However, poor knowledge of PD and PD as risk factor for some systemic illnesses, coupled with unsatisfactory oral hygiene and dental examination practices are evident among the doctors. PMID- 27182521 TI - BRACHIAL PLEXUS BLOCK FOR UPPER LIMB PROCEDURES: EXPERIENCE AT THE UNIVERSITY OF UYO TEACHING HOSPITAL, UYO, AKWA IBOM STATE, NIGERIA. AB - BACKGROUND: Brachial plexus block (BPB) has many benefits over general anaesthesia in upper limb procedures. However, its utilization in Nigeria is not as high as expected. AIM: To evaluate BPB in upper limb surgeries, its utilization, outcome and complication profile. MATERIALS AND METHODS: Approval for the study was obtained from the institution's research ethical committee. This was a retrospective study of all patients who underwent upper limb surgeries from May 2011 to December 2014. Those who had BPB were further analysed. Data was obtained from the anaesthesia register and records, as well as the patients' folders. Information obtained included: age, gender, ASA class, type of BPB and nerve localization technique. The primary outcome was the adequacy of the block for surgery and complications. Data analysis was done using SPSS, version 16. RESULTS: Ninety two patients underwent upper limb surgeries, out of which 42(45.65%) were performed under BPB, the rest were done under GA-45(48.91%), local infiltration-4(4.35%) or wrist block-1(1.09%). Combined interscalene and axillary blocks were performed in 35(83.3%) patients, interscalene block only 5(11.9%), combined interscalene and supraclavicular blocks, and axillary block only in 1(2.4%) patient each. Paraesthesia technique-40(95.2%) was the dominant nerve localization technique, while nerve stimulator was used in 2(4.8%) patients only. BPB was adequate in 37(88.1%) patients, while it failed in only 5(11.9%) patients, and were converted to GA. No major complication was observed except dysthesia reported in 1(2.4%) patient postoperatively. CONCLUSION: The use of brachial plexus block for upper limb procedure in our centre is rising. Paraesthesia technique is predominant, and it is associated with a high success rate and low complications. PMID- 27182522 TI - Comming of Age! : Inaugural Address of Professor Akinyinka O. Omigbodun, 28(th) President of the West African College of Surgeons. PMID- 27182523 TI - 55(th) ANNUAL CONFERENCE OF THE WEST AFRICAN COLLEGE OF SURGEONS (WACS) AT ABIDJAN, COTE D'IVOIRE. PMID- 27182524 TI - PEER-REVIEWED ABSTRACTS OF SCIENTIFIC PAPER PRESENTATION AT THE 55th ANNUAL CONFERENCE OF THE WEST AFRICAN COLLEGE OF SURGEONS AT ABIDJAN, COTE D'IVOIRE 2nd 6th MARCH 2015. PMID- 27182525 TI - THE WEST AFRICAN COLLEGE OF SURGEONS ANNUAL CONFERENCES 1960-2015. PMID- 27182526 TI - Sleep-disordered breathing and stroke: A relation to be considered. AB - Stroke is a leading cause of death and disability. Despite expensive and elaborative research in finding out mechanisms of interrelation between sleep disordered breathing (SDB) and stroke, there is yet much attention to be given in stroke units worldwide to the prompt diagnosis and treatment of SDB in order to improve morbidity and mortality rates related with stroke. The preventive diagnosis and treatment of SDB reduce stroke rate and improves penumbra area in case of ischemic stroke. Stroke itself predispose to SDB, making the interrelationship more complicated. The review by Parra O and Arboix A reflects the results from carefully selected reviews reported in the literature so far. This review of the literature and presentation of the original study of the Authors based on their patients' data, enhances the conviction that there exists a direct relation between SDB and stroke. Diagnosis of SDB in new stroke cases should be sought and treated carefully whenever present. PMID- 27182527 TI - Cardiac resynchronisation therapy after percutaneous mitral annuloplasty. AB - Percutaneous approaches to reduce mitral regurgitation in ischemic cardiomyopathy have stirred interest recently. Patients with ischemic cardiomyopathy and functional mitral regurgitation often meet criteria for cardiac resynchronisation therapy to improve left ventricular function as well as mitral regurgitation, and alleviate symptoms. This case shows that implantation of a pacing lead in the coronary sinus to restore synchronous left and right ventricular contraction is feasible, despite the presence of a remodeling device in the coronary sinus. PMID- 27182528 TI - Sepsis associated delirium mimicking postoperative delirium as the initial presenting symptom of urosepsis in a patient who underwent nephrolithotomy. AB - We report a case of 70 years old male who underwent percutaneous nephrolithotomy for renal calculi. After an uneventful recovery from anaesthesia, the patient developed delirium which manifested as restlessness, agitation, irritability and combative behavior. All other clinical parameters including arterial blood gas, chest X-ray and core temperature were normal and the patient remained haemodynamically stable. But 45 min later the patient developed florid manifestations of septic shock. He was aggressively managed in a protocolized manner as per the Surviving Sepsis Guidelines in the Critical Care Unit and recovered completely. There are no case reports showing postoperative delirium as the only initial presentation of severe sepsis, with other clinical parameters remaining normal. Both urosepsis and sepsis associated delirium have very high mortality. High index of suspicion and a protocolized approach in the management of sepsis can save lives. PMID- 27182529 TI - Removal of a large foreign body in the rectosigmoid colon by colonoscopy using gastrolith forceps. AB - Rectal foreign bodies are man-made injury that occurs occasionally. The management depends on its depth and the consequence it caused. We here report a case of rectal foreign body (a glass bottle measuring about 38 mm * 75 mm) which was located 13-15 cm from the anus. The patient had no sign of perforation, and we managed to remove it using endoscopy with gastrolith forceps. PMID- 27182531 TI - A Coaxial Dielectric Probe Technique for Distinguishing Tooth Enamel from Dental Resin. AB - For purposes of biodosimetry in the event of a large scale radiation disaster, one major and very promising point-of contact device is assessing dose using tooth enamel. This technique utilizes the capabilities of electron paramagnetic resonance to measure free radicals and other unpaired electron species, and the fact that the deposition of energy from ionizing radiation produces free radicals in most materials. An important stipulation for this strategy is that the measurements, need to be performed on a central incisor that is basically intact, i.e. which has an area of enamel surface that is as large as the probing tip of the resonator that is without decay or restorative care that replaces the enamel. Therefore, an important consideration is how to quickly assess whether the tooth has sufficient enamel to be measured for dose and whether there is resin present on the tooth being measured and to be able to characterize the amount of surface that is impacted. While there is a relatively small commercially available dielectric probe which could be used in this context, it has several disadvantages for the intended use. Therefore, a smaller, 1.19mm diameter 50 ohm, open-ended, coaxial dielectric probe has been developed as an alternative. The performance of the custom probe was validated against measurement results of known standards. Measurements were taken of multiple teeth enamel and dental resin samples using both probes. While the probe contact with the teeth samples was imperfect and added to measurement variability, the inherent dielectric contrast between the enamel and resin was sufficient that the probe measurements could be used as a robust means of distinguishing the two material types. The smaller diameter probe produced markedly more definitive results in terms of distinguishing the two materials. PMID- 27182532 TI - Engineering Near-Field SEIRA Enhancements in Plasmonic Resonators. AB - Engineering of the optical resonances in plasmonic resonators arrays is achieved by virtue of the intrinsic properties to the constituent structures such as composition, size and shape and by controlling the inter-resonator interactions by of virtue the array geometrical arrangement. The nanoscale confinement of the plasmonic field enhances light-matter interactions enabling, for instance, the surface enhanced infrared absorption (SEIRA) effect. However, the subwavelength confinement also poses an experimental challenge for discriminating the response stemming from the individual resonators and from the collective response in densely packed arrays. In this work, the photothermal induced resonance (PTIR) technique is leveraged to obtain nanoscale images and spectra of near-field SEIRA hot spots observed in isolated plasmonic resonators of different shapes and in selected resonators within closely packed plasmonic arrays informing on whether the interactions with neighboring resonators are beneficial or otherwise. Results are correlated with far-field spectra and theoretical calculations. PMID- 27182533 TI - A translational consideration of intercellular adhesion molecule-1 biology in the perioperative setting. AB - Intercellular adhesion molecule-1 (ICAM-1) is a critical adhesion molecule involved in leukocyte recruitment. Since its discovery in 1986, a large number of studies have been performed to elucidate its role in vitro and in vivo. Here, we review its role in leukocyte recruitment and consider future steps to take that will enhance our understanding of ICAM-1 biology and its translational application in the perioperative setting. PMID- 27182534 TI - Electron Paramagnetic Resonance (EPR) Spectroscopy to Detect Reactive Oxygen Species in Staphylococcus aureus. AB - Under aerobic conditions, Staphylococcus aureus (S. aureus) primarily metabolizes glucose to acetic acid. Although normally S. aureus is able to re-utilize acetate as a carbon source following glucose exhaustion, significantly high levels of acetate in the culture media may not only be growth inhibitory but also potentiates cell death in stationary phase cultures by a mechanism dependent on cytoplasmic acidification. One consequence of acetic acid toxicity is the production of reactive oxygen species (ROS). The present protocol describes the detection of ROS in S. aureus undergoing cell death by electron paramagnetic resonance (EPR) spectroscopy. Using 1-hydroxy-3-methoxycarbonyl-2,2,5,5 tetramethylpyrrolidine (CMH) as a cell permeable spin probe, we demonstrate the detection of various oxygen radicals generated by bacteria. Although standardized for S. aureus, the methods described here should be easily adapted for other bacterial species. This protocol is adapted from Thomas et al. (2014) and Thomas et al. (2010). PMID- 27182535 TI - Telomerase Repeated Amplification Protocol (TRAP). AB - Telomeres are found at the end of eukaryotic linear chromosomes, and proteins that bind to telomeres protect DNA from being recognized as double-strand breaks thus preventing end-to-end fusions (Griffith et al., 1999). However, due to the end replication problem and other factors such as oxidative damage, the limited life span of cultured cells (Hayflick limit) results in progressive shortening of these protective structures (Hayflick and Moorhead, 1961; Olovnikov, 1973). The ribonucleoprotein enzyme complex telomerase-consisting of a protein catalytic component hTERT and a functional RNA component hTR or hTERC- counteracts telomere shortening by adding telomeric repeats to the end of chromosomes in ~90% of primary human tumors and in some transiently proliferating stem-like cells (Shay and Wright, 1996; Shay and Wright, 2001). This results in continuous proliferation of cells which is a hallmark of cancer. Therefore, telomere biology has a central role in aging, cancer progression/metastasis as well as targeted cancer therapies. There are commonly used methods in telomere biology such as Telomere Restriction Fragment (TRF) (Mender and Shay, 2015b), Telomere Repeat Amplification Protocol (TRAP) and Telomere dysfunction Induced Foci (TIF) analysis (Mender and Shay, 2015a). In this detailed protocol we describe Telomere Repeat Amplification Protocol (TRAP). The TRAP assay is a popular method to determine telomerase activity in mammalian cells and tissue samples (Kim et al., 1994). The TRAP assay includes three steps: extension, amplification, and detection of telomerase products. In the extension step, telomeric repeats are added to the telomerase substrate (which is actually a non telomeric oligonucleotide, TS) by telomerase. In the amplification step, the extension products are amplified by the polymerase chain reaction (PCR) using specific primers (TS upstream primer and ACX downstream primer) and in the detection step, the presence or absence of telomerase is analyzed by electrophoresis. TSNT is, an internal standard control, amplified by TS primer. NT is its own reverse primer, which is not a substrate for telomerase. These primers are used to identify false negative results by if the gel lacks internal control bands. PMID- 27182530 TI - Can you hear me yet? An intracranial investigation of speech and non-speech audiovisual interactions in human cortex. AB - In everyday conversation, viewing a talker's face can provide information about the timing and content of an upcoming speech signal, resulting in improved intelligibility. Using electrocorticography, we tested whether human auditory cortex in Heschl's gyrus (HG) and on superior temporal gyrus (STG) and motor cortex on precentral gyrus (PreC) were responsive to visual/gestural information prior to the onset of sound and whether early stages of auditory processing were sensitive to the visual content (speech syllable versus non-speech motion). Event related band power (ERBP) in the high gamma band was content-specific prior to acoustic onset on STG and PreC, and ERBP in the beta band differed in all three areas. Following sound onset, we found with no evidence for content-specificity in HG, evidence for visual specificity in PreC, and specificity for both modalities in STG. These results support models of audio-visual processing in which sensory information is integrated in non-primary cortical areas. PMID- 27182536 TI - Preparation of Synaptosomes from the Motor Cortex of Motor Skill Trained Mice. AB - Learning and memory are thought to occur due to changes in synaptic strength. Strengthening of synapses due to Long Term Potentiation mechanisms are mediated by increases in synaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) levels. Here we describe a protocol to isolate and quantify synaptic AMPAR subunit GluA1 levels from the motor cortex of mice which have undergone motor skill training. PMID- 27182538 TI - Upcycling potato peel waste - Data of the pre-screening of the acid-catalyzed liquefaction. AB - Herein, the data acquired regarding the preliminary and exploratory experiments conducted with potato peel as a biomass source for the direct thermochemical liquefaction is disclosed. The procedure was carried out in a 2-ethylhexanol/DEG solvent mixture at 160 degrees C in the presence of p-Toluenesulfonic acid. The adopted procedure afforded a bio-oil in high yield (up to 93%) after only 30 min. For longer reaction times, higher amounts of solid residues were obtained leading, consequently, to lower yields. PMID- 27182539 TI - Retrospective analysis of cohort database: Phenotypic variability in a large dataset of patients confirmed to have homozygous familial hypercholesterolemia. AB - These data describe the phenotypic variability in a large cohort of patients confirmed to have homozygous familial hypercholesterolemia. Herein, we describe the observed relationship of treated low-density lipoprotein cholesterol with age. We also overlay the low-density lipoprotein receptor gene (LDLR) functional status with these phenotypic data. A full description of these data is available in our recent study published in Atherosclerosis, "Phenotype Diversity Among Patients With Homozygous Familial Hypercholesterolemia: A Cohort Study" (Raal et al., 2016) [1]. PMID- 27182537 TI - Neural Markers of the Development of Executive Function: Relevance for Education. AB - Executive functions are involved in the development of academic skills and are critical for functioning in school settings. The relevance of executive functions to education begins early and continues throughout development, with clear impact on achievement. Diverse efforts increasingly suggest ways in which facilitating development of executive function may be used to improve academic performance. Such interventions seek to alter the trajectory of executive development, which exhibits a protracted course of maturation that stretches into young adulthood. As such, it may be useful to understand how the executive system develops normally and abnormally in order to tailor interventions within educational settings. Here we review recent work investigating the neural basis for executive development during childhood and adolescence. PMID- 27182541 TI - Data on litter quality of host grass plants with and without fungal endophytes. AB - Certain Pooideae species form persistent symbiosis with fungal endophytes of Epichloe genus. Although endophytes are known to impact the ecology and evolution of host species, their effects on parameters related with quality of plant biomass has been elusive. This article provides information about parameters related with the quality of plant litter biomass of two important grass species (Schedonorus phoenix and Schedonorus pratensis) affected by the symbiosis with fungal endophytes (Epichloe coenophiala and Epichloe uncinata, respectively). Four population origins of S. phoenix and one of S. pratensis were included. Mineral, biochemical and structural parameters were obtained from three samples per factors combination [species (and population origin)*endophyte]. This data can be potentially used in other studies which, by means of 'data reanalyzing' or meta-analysis, attempt to find generalizations about endophyte effects on host plant litter biomass. The present data is associated with the research article "Role of foliar fungal endophytes on litter decomposition among species and population origins" (Gundel et al., In preparation) [1]. PMID- 27182540 TI - Time-resolved visible and infrared absorption spectroscopy data obtained using photosystem I particles with non-native quinones incorporated into the A1 binding site. AB - Time-resolved visible and infrared absorption difference spectroscopy data at both 298 and 77 K were obtained using cyanobacterial menB (-) mutant photosystem I particles with several non-native quinones incorporated into the A1 binding site. Data was obtained for photosystem I particles with phylloquinone (2-methyl 3-phytyl-1,4-naphthoquinone), 2-bromo-1,4-naphthoquinone, 2-chloro-1,4 naphthoquinone, 2-methyl-1,4-naphthoquinone, 2,3-dibromo-1,4-naphthoquinone, 2,3 dichloro-1,4-naphthoquinone, and 9,10-anthraquinone incorporated. Transient absorption data were obtained at 487 and 703 nm in the visible spectral range, and 1950-1100 cm(-1) in the infrared region. Time constants obtained from fitting the time-resolved infrared and visible data are in good agreement. The measured time constants are crucial for the development of appropriate kinetic models that can describe electron transfer processes in photosystem I, "Modeling Electron Transfer in Photosystem I" Makita and Hastings (2016) [1]. PMID- 27182542 TI - Innovation in urban agriculture: Evaluation data of a participatory approach (ROIR). AB - The data in this article represent an evaluation of a participatory process called Regional Open Innovation Roadmapping (ROIR). The approach aims at the promotion of regional development. In this case, it was carried out to develop a specific innovation in the field of 'Zero-acreage farming' (ZFarming), which is a building-related subtype of urban agriculture. For the evaluation of the process, an online survey was sent to the 58 participants of the ROIR on March 4, 2014. The survey ended on April 8, 2014, and a response rate of 53.54% resulted in a sample size of 31 respondents. The survey was divided into seven different blocks. We analyzed the ROIR process's contribution to knowledge generation, the establishment of networks among the participants, the implementation of new projects related to ZFarming, and the increase of acceptance of ZFarming and the selected ZFarming innovation. Furthermore, other remarks, and personal information were collected. Hence, the objective of the survey was to assess whether ROIR is a useful tool to promote the aforementioned innovation drivers, and thereby, the selected innovation, which was developed throughout the process. The data were used in the research article "Application and evaluation of a participatory "open innovation" approach (ROIR): the case of introducing zero acreage farming in Berlin" (Specht et al., 2016) [1]. PMID- 27182543 TI - Dataset of UV induced changes in nuclear proteome obtained by GeLC-Orbitrap/MS in Pinus radiata needles. AB - Although responses to UV stress have been characterised at system and cellular levels, the dynamics of the nuclear proteome triggered in this situation are still unknown, despite its essential role in regulating gene expression and in last term plant physiology. To fill this gap, we characterised the variations in the nuclear proteome after 2 h and 16 h (8 h/day) of UV irradiation by using state-of-the-art mass spectrometry-based shotgun proteomics methods combined with novel bioinformatics workflows that were employed in the manuscript entitled "The variations in the nuclear proteome reveal new transcription factors and mechanisms involved in UV stress response in Pinus radiata" (Pascual et al., 2016) [1]. We employed in-gel digestion followed by a 120 min gradient prior to MS analysis. Data was processed following two approaches: a database dependent employing the SEQUEST algorithm and custom databases, and a database independent by mass accuracy precursor alignment (MAPA). 388 proteins were identified by SEQUEST search and 9094 m/z were quantified by MAPA. Significant m/z were de novo sequenced using the Novor algorithm. We present here the complete datasets and the analysis workflow. PMID- 27182544 TI - Spectral reflectance data of a high temperature stable solar selective coating based on MoSi2 -Si3N4. AB - Data of optical performance, thermal stability and ageing are given for solar selective coatings (SSC) based on a novel MoSi2-Si3N4 absorbing composite. SSC have been prepared as multilayer stacks formed by silver as metallic infrared reflector, a double layer composite and an antireflective layer (doi: 10.1016/j.solmat.2016.04.001 [1]). Spectroscopic reflectance data corresponding to the optical performance of samples after moderate vacuum annealing at temperatures up to 600 degrees C and after ageing test of more than 200 h with several heating-cooling cycles are shown here. PMID- 27182545 TI - Data in support of the bone analysis of NOD-SCID mice treated with zoledronic acid and prednisolone. AB - This paper reports data on the bone, specifically the tibia and mandible, of nonobese diabetic mice with severe combined immunodeficiency disease (NOD-SCID mice) treated with zoledronic acid (ZA) and prednisolone (PSL). The data described here are related to the research article titled "Zoledronic acid basically increases circulating soluble RANKL level in mice, and in glucocorticoid-administrated mice, more increases lymphocytes derived sRANKL by bacterial endotoxic stimuli" [1]. The present data and the NOD-SCID mice experiments described contain insights into the role of bone-remodeling factors induced by ZA treatment. PMID- 27182546 TI - RNA-sequencing data analysis of uterus in ovariectomized rats fed with soy protein isolate, 17beta-estradiol and casein. AB - This data file describes the bioinformatics analysis of uterine RNA-seq data comparing genome wide effects of feeding soy protein isolate compared to casein to ovariectomized female rats age 64 days relative to treatment of casein fed rats with 5 MUg/kg/d estradiol and relative to rats treated with estradiol and also fed soy protein isolate. Complete raw data files were deposited in the gene Expression Omnibus (GEO) at NCBI (http:/www.ncbi.nlm.nih.gov.geo/) under the GEO accession number GEO: GSE69819. Data presented here incudes a summary of the differential expression analysis with top 30 genes up- and down-regulated by soy protein isolate (SPI), estradiol (E2) and SPI+E2. Additional functional annotation analysis of KEGG pathways is also presented for each treatment, together with networks of interaction between those pathways. Further interpretation and discussion of this data can be found in the article "Uterine responses to feeding soy protein isolate and treatment with 17beta-estradiol differ in ovariectomized female rats" Ronis et al. (2016) [1]. PMID- 27182547 TI - Proteomic dataset of the sea urchin Paracentrotus lividus adhesive organs and secreted adhesive. AB - Sea urchins have specialized adhesive organs called tube feet, which mediate strong but reversible adhesion. Tube feet are composed by a disc, producing adhesive and de-adhesive secretions for substratum attachment, and a stem for movement. After detachment the secreted adhesive remains bound to the substratum as a footprint. Recently, a label-free quantitative proteomic approach coupled with the latest mass-spectrometry technology was used to analyze the differential proteome of Paracentrotus lividus adhesive organ, comparing protein expression levels in the tube feet adhesive part (the disc) versus the non-adhesive part (the stem), and also to profile the proteome of the secreted adhesive (glue). This data article contains complementary figures and results related to the research article "Deciphering the molecular mechanisms underlying sea urchin reversible adhesion: a quantitative proteomics approach" (Lebesgue et al., 2016) [1]. Here we provide a dataset of 1384 non-redundant proteins, their fragmented peptides and expression levels, resultant from the analysis of the tube feet differential proteome. Of these, 163 highly over-expressed tube feet disc proteins (>3-fold), likely representing the most relevant proteins for sea urchin reversible adhesion, were further annotated in order to determine the potential functions. In addition, we provide a dataset of 611 non-redundant proteins identified in the secreted adhesive proteome, as well as their functional annotation and grouping in 5 major protein groups related with adhesive exocytosis, and microbial protection. This list was further analyzed to identify the most abundant protein groups and pinpoint putative adhesive proteins, such as Nectin, the most abundant adhesive protein in sea urchin glue. The obtained data uncover the key proteins involved in sea urchins reversible adhesion, representing a step forward to the development of new wet-effective bio-inspired adhesives. PMID- 27182548 TI - Cytotoxic data of 14-deoxy-11, 12-didehydroandrographolide (14-DDA), double transfection and DDIT3 silencing data in T-47D breast carcinoma cells. AB - The data presented in this article are related to the research article entitled "14-deoxy-11,12-didehydroandrographolide induces DDIT3-dependent endoplasmic reticulum stress-mediated autophagy in T-47D breast carcinoma cells", which the mechanistic toxicology properties of 14-deoxy-11,12-didehydroandrographolide (14 DDA) were investigated (Tan et al., 2016 [1]). This article describes the derivation of cytotoxic parameters of 14-DDA, cell viability data after double transfection and DDIT3 silencing in T-47D cells. PMID- 27182549 TI - Bioinformatics data supporting revelatory diversity of cultivable thermophiles isolated and identified from two terrestrial hot springs, Unkeshwar, India. AB - A total of 21 thermophilic bacteria were isolated and identified using 16S rRNA gene sequencing method. Sequences were submitted to NCBI website. Short DNA sequences JN392966-JN392972; KC120909-KC120919; KM998072-KM998074 and KP053645 strains were downloaded from NCBI BioSample database. ENDMEMO GC calculating tool was used for calculation of maximum, minimum and average GC percentage and graphical representation of GC content. Data generated indicate 20 short DNA sequences have maximum GC content ranged from 60% to 100% with an average GC content 52.5-59.8%. It is recorded that Bacillus sp. W7, Escherichia coli strain NW1 and Geobacillus thermoleovorans strain rekadwadsis strains showed GC content maximum up to 70%; Actinobacterium EF_NAK1-7 up to 85.7%, while Bacillus megaterium and E. coli strain NW2 showed GC content maximum to 100%. Digital data on thermophilic bacteria isolated from Unkeshwar hot springs would be useful for interpretation of presence of biodiversity in addition to phenotypic, physiological characteristics and data generated through 16S rRNA gene sequencing technology. PMID- 27182550 TI - Proteome dataset of pre-ovulatory follicular fluids from less fertile dairy cows. AB - This article contains raw and processed data related to research published in Zachut et al. (2016) [1]. Proteomics data from preovulatory follicles in cows was obtained by liquid chromatography-mass spectrometry following protein extraction. Differential expression between controls and less fertile cows (LFC) was quantified using MS1 intensity based label-free. The only previous proteomic analysis of bovine FF detected merely 40 proteins in follicular cysts obtained from the slaughterhouse (Maniwa et al., 2005) [2], and the abundance of proteins in the bovine preovulatory FF remains unknown. Therefore, the objectives were to establish the first dataset of FF proteome in preovulatory follicles of cows, and to examine differentially expressed proteins in FF obtained in-vivo from preovulatory follicles of less fertile cows (also termed "repeat breeder") and control (CTL) cows. The proteome of FF from 10 preovulatory follicles that were aspirated in vivo (estradiol/progesterone>1) was analyzed. This novel dataset contains 219 identified and quantified proteins in FF, consisting mainly of binding proteins, proteases, receptor ligands, enzymes and transporters. In addition, differential abundance of 8 proteins relevant to follicular function was found in LFC compared to CTL; these findings are discussed in our recent research article Zachut et al. (2016) [1]. The present dataset of bovine FF proteome can be used as a reference for any study involving disorders of follicular development in dairy cows or in comparative studies between species. PMID- 27182551 TI - EnABLing microprocessor for apoptosis. AB - The Microprocessor complex consisting of DROSHA (a type III ribonuclease) and DGCR8 (DiGeorge syndrome critical region gene 8-encoded RNA binding protein) recognizes and cleaves the precursor microRNA hairpin (pre-miRNA) from the primary microRNA transcript (pri-miRNA). The Abelson tyrosine kinase 1 (ABL) phosphorylates DGCR8 to stimulate the cleavage of a subset of pro-apoptotic pri miRNAs, thus expanding the nuclear functions of ABL to include regulation of RNA processing. PMID- 27182553 TI - Genomic mechanisms underlying PARK2 large deletions identified in a cohort of patients with PD. AB - OBJECTIVES: To identify the genomic mechanisms that result in PARK2 large gene deletions. METHODS: We conducted mutation screening using PCR amplification of PARK2-coding regions and exon-intron boundaries, followed by sequencing to evaluate a large series of 244 unrelated Portuguese patients with symptoms of Parkinson disease. For the detection of large gene rearrangements, we performed multiplex ligation-dependent probe amplification, followed by long-range PCR and sequencing to map deletion breakpoints. RESULTS: We identified biallelic pathogenic parkin mutations in 40 of the 244 patients. There were 18 different mutations, some of them novel. This study included mapping of 17 deletion breakpoints showing that nonhomologous end joining is the most common mechanism responsible for these gene rearrangements. None of these deletion breakpoints were previously described, and only one was present in 2 unrelated families, indicating that most of the deletions result from independent events. CONCLUSIONS: The c.155delA mutation is highly prevalent in the Portuguese population (62.5% of the cases). Large deletions were present in 42.5% of the patients. We present the largest study on the molecular mechanisms that mediate PARK2 deletions in a homogeneous population. PMID- 27182552 TI - Neuronal and Astrocytic Monoacylglycerol Lipase Limit the Spread of Endocannabinoid Signaling in the Cerebellum. AB - Endocannabinoids are diffusible lipophilic molecules that may spread to neighboring synapses. Monoacylglycerol lipase (MAGL) is the principal enzyme that degrades the endocannabinoid 2-arachidonoylglycerol (2-AG). Using knock-out mice in which MAGL is deleted globally or selectively in neurons and astrocytes, we investigated the extent to which neuronal and astrocytic MAGL limit the spread of 2-AG-mediated retrograde synaptic depression in cerebellar slices. A brief tetanic stimulation of parallel fibers in the molecular layer induced synaptically evoked suppression of excitation (SSE) in Purkinje cells, and both neuronal and astrocytic MAGL contribute to the termination of this form of endocannabinoid-mediated synaptic depression. The spread of SSE among Purkinje cells occurred only after global knock-out of MAGL or pharmacological blockade of either MAGL or glutamate uptake, but no spread was detected following neuron- or astrocyte-specific deletion of MAGL. The spread of endocannabinoid signaling was also influenced by the spatial pattern of synaptic stimulation, because it did not occur at spatially dispersed parallel fiber synapses induced by stimulating the granular layer. The tetanic stimulation of parallel fibers did not induce endocannabinoid-mediated synaptic suppression in Golgi cells even after disruption of MAGL and glutamate uptake, suggesting that heightened release of 2 AG by Purkinje cells does not spread the retrograde signal to parallel fibers that innervate Golgi cells. These results suggest that both neuronal and astrocytic MAGL limit the spatial diffusion of 2-AG and confer synapse specificity of endocannabinoid signaling. PMID- 27182554 TI - Integrated expression analysis of muscle hypertrophy identifies Asb2 as a negative regulator of muscle mass. AB - The transforming growth factor-beta (TGF-beta) signaling network is a critical regulator of skeletal muscle mass and function and, thus, is an attractive therapeutic target for combating muscle disease, but the underlying mechanisms of action remain undetermined. We report that follistatin-based interventions (which modulate TGF-beta network activity) can promote muscle hypertrophy that ameliorates aging-associated muscle wasting. However, the muscles of old sarcopenic mice demonstrate reduced response to follistatin compared with healthy young-adult musculature. Quantitative proteomic and transcriptomic analyses of young-adult muscles identified a transcription/translation signature elicited by follistatin exposure, which included repression of ankyrin repeat and SOCS box protein 2 (Asb2). Increasing expression of ASB2 reduced muscle mass, thereby demonstrating that Asb2 is a TGF-beta network-responsive negative regulator of muscle mass. In contrast to young-adult muscles, sarcopenic muscles do not exhibit reduced ASB2 abundance with follistatin exposure. Moreover, preventing repression of ASB2 in young-adult muscles diminished follistatin-induced muscle hypertrophy. These findings provide insight into the program of transcription and translation events governing follistatin-mediated adaptation of skeletal muscle attributes and identify Asb2 as a regulator of muscle mass implicated in the potential mechanistic dysfunction between follistatin-mediated muscle growth in young and old muscles. PMID- 27182555 TI - PD-1 marks dysfunctional regulatory T cells in malignant gliomas. AB - Immunotherapies targeting the immune checkpoint receptor programmed cell death protein 1 (PD-1) have shown remarkable efficacy in treating cancer. CD4+CD25hiFoxP3+ Tregs are critical regulators of immune responses in autoimmunity and malignancies, but the functional status of human Tregs expressing PD-1 remains unclear. We examined functional and molecular features of PD-1hi Tregs in healthy subjects and patients with glioblastoma multiforme (GBM), combining functional assays, RNA sequencing, and cytometry by time of flight (CyTOF). In both patients with GBM and healthy subjects, circulating PD-1hi Tregs displayed reduced suppression of CD4+ effector T cells, production of IFN-gamma, and molecular signatures of exhaustion. Transcriptional profiling of tumor resident Tregs revealed that several genes coexpressed with PD-1 and associated with IFN-gamma production and exhaustion as well as enrichment in exhaustion signatures compared with circulating PD-1hi Tregs. CyTOF analysis of circulating and tumor-infiltrating Tregs from patients with GBM treated with PD-1-blocking antibodies revealed that treatment shifts the profile of circulating Tregs toward a more exhausted phenotype reminiscent of that of tumor-infiltrating Tregs, further increasing IFN-gamma production. Thus, high PD-1 expression on human Tregs identifies dysfunctional, exhausted Tregs secreting IFN-gamma that exist in healthy individuals and are enriched in tumor infiltrates, possibly losing function as they attempt to modulate the antitumoral immune responses. PMID- 27182556 TI - T cell Bim levels reflect responses to anti-PD-1 cancer therapy. AB - Immune checkpoint therapy with PD-1 blockade has emerged as an effective therapy for many advanced cancers; however, only a small fraction of patients achieve durable responses. To date, there is no validated blood-based means of predicting the response to PD-1 blockade. We report that Bim is a downstream signaling molecule of the PD-1 pathway, and its detection in T cells is significantly associated with expression of PD-1 and effector T cell markers. High levels of Bim in circulating tumor-reactive (PD-1+CD11ahiCD8+) T cells were prognostic of poor survival in patients with metastatic melanoma who did not receive anti-PD-1 therapy and were also predictive of clinical benefit in patients with metastatic melanoma who were treated with anti-PD-1 therapy. Moreover, this circulating tumor-reactive T cell population significantly decreased after successful anti-PD 1 therapy. Our study supports a crucial role of Bim in both T cell activation and apoptosis as regulated by PD-1 and PD-L1 interactions in effector CD8+ T cells. Measurement of Bim levels in circulating T cells of patients with cancer may provide a less invasive strategy to predict and monitor responses to anti-PD-1 therapy, although future prospective analyses are needed to validate its utility. PMID- 27182557 TI - Multiplexed immunofluorescence delineates proteomic cancer cell states associated with metabolism. AB - The phenotypic diversity of cancer results from genetic and nongenetic factors. Most studies of cancer heterogeneity have focused on DNA alterations, as technologies for proteomic measurements in clinical specimen are currently less advanced. Here, we used a multiplexed immunofluorescence staining platform to measure the expression of 27 proteins at the single-cell level in formalin-fixed and paraffin-embedded samples from treatment-naive stage II/III human breast cancer. Unsupervised clustering of protein expression data from 638,577 tumor cells in 26 breast cancers identified 8 clusters of protein coexpression. In about one-third of breast cancers, over 95% of all neoplastic cells expressed a single protein coexpression cluster. The remaining tumors harbored tumor cells representing multiple protein coexpression clusters, either in a regional distribution or intermingled throughout the tumor. Tumor uptake of the radiotracer 18F-fluorodeoxyglucose was associated with protein expression clusters characterized by hormone receptor loss, PTEN alteration, and HER2 gene amplification. Our study demonstrates an approach to generate cellular heterogeneity metrics in routinely collected solid tumor specimens and integrate them with in vivo cancer phenotypes. PMID- 27182558 TI - Alk5 inhibition increases delivery of macromolecular and protein-bound contrast agents to tumors. AB - Limited transendothelial permeability across tumor microvessels represents a significant bottleneck in the development of tumor-specific diagnostic agents and theranostic drugs. Here, we show an approach to increase transendothelial permeability of macromolecular and nanoparticle-based contrast agents via inhibition of the type I TGF-beta receptor, activin-like kinase 5 (Alk5), in tumors. Alk5 inhibition significantly increased tumor contrast agent delivery and enhancement on imaging studies, while healthy organs remained relatively unaffected. Imaging data correlated with significantly decreased tumor interstitial fluid pressure, while tumor vascular density remained unchanged. This immediately clinically translatable concept involving Alk5 inhibitor pretreatment prior to an imaging study could be leveraged for improved tumor delivery of macromolecular and nanoparticle-based imaging probes and, thereby, facilitate development of more sensitive imaging tests for cancer diagnosis, enhanced tumor characterization, and personalized, image-guided therapies. PMID- 27182560 TI - Exenatide Effects on Cardiometabolic Risk and Weight in Adolescents with Morbid Obesity and Type 2 Diabetes Mellitus: Two Case Reports. AB - OBJECTIVE: Glucagon-like peptide-1 (GLP-1) receptor agonists improve glycemic control and cardiometabolic risk factors in adults with type 2 diabetes mellitus, but pediatric data is sparse. RESEARCH DESIGN AND METHODS: This is the first report to describe the effects of GLP-1 receptor agonist Exenatide on metabolic risk and weight in adolescents with morbid obesity (BMI>35kg/m2) and type 2 diabetes in the first 6 months after treatment initiation. Two patients with morbid obesity who failed conventional therapy with insulin glargine and Metformin were treated with the addition of Exenatide. Metabolic parameters were obtained at 3 and 6 months post intervention. RESULTS: Improvements in cardiometabolic risk factors, such as fasting glucose and triglyceride levels, as well as HbA1c, were reached at 6 months compared to baseline. CONCLUSIONS: Our cases highlight the therapeutic potential of exenatide for adolescent patients with morbid obesity and type 2 diabetes. PMID- 27182559 TI - T cell ignorance is bliss: T cells are not tolerized by Langerhans cells presenting human papillomavirus antigens in the absence of costimulation. AB - Human papillomavirus type 16 (HPV16) infections are intra-epithelial, and thus, HPV16 is known to interact with Langerhans cells (LCs), the resident epithelial antigen-presenting cells (APCs). The current paradigm for APC-mediated induction of T cell anergy is through delivery of T cell receptor signals via peptides on MHC molecules (signal 1), but without costimulation (signal 2). We previously demonstrated that LCs exposed to HPV16 in vitro present HPV antigens to T cells without costimulation, but it remained uncertain if such T cells would remain ignorant, become anergic, or in the case of CD4+ T cells, differentiate into Tregs. Here we demonstrate that Tregs were not induced by LCs presenting only signal 1, and through a series of in vitro immunizations show that CD8+ T cells receiving signal 1 + 2 from LCs weeks after consistently receiving signal 1 are capable of robust effector functions. Importantly, this indicates that T cells are not tolerized but instead remain ignorant to HPV, and are activated given the proper signals. PMID- 27182562 TI - Human Touch in Digital Experiences. PMID- 27182561 TI - Brief Interventions for Adolescents. AB - Public health concerns regarding adolescent alcohol and other drug involvement emphasize the need for continuing research to develop and evaluate preventive interventions for use in a variety of settings. This focus includes research on brief interventions. This short commentary piece provides an overview of the brief intervention literature and highlights future directions. PMID- 27182563 TI - [Peculiarities of oral health of organized collectives and professional communities]. AB - The analysis of scientific literature on the peculiarities of the dental status of organized groups and professional associations. After reviewing the literature, it becomes clear that the studies carried out in organized groups and professional societies are very relevant today, because the prevalence of dental diseases among them remains high, fueled by a number of factors: habitat, diet, lifestyle, occupational hazards, particularly hygienic oral care. Nowadays there is no information about the features of the dental status among the clergy, whose professional activity is connected with direct close contact with people. This profession covers a large number of our population. The research of certain groups is of special interest, since a number of different factors affect dental health. PMID- 27182564 TI - [Clinical and pathogenetic aspects of various forms of cheilitis]. PMID- 27182565 TI - [On the question of dental implantation follow-up and results assessment in patients with risk factors]. PMID- 27182566 TI - Author Response: Alex B. Munster, Angelo J. Franchini, Mahim I. Qureshi, Ankur Thapar, Alun H. Davies, London. PMID- 27182567 TI - Mitchell P. Fink, Associate Editor: A Remembrance. PMID- 27182568 TI - A New Collaboration Between the Canadian Association for Neuroscience and CJNS. PMID- 27182569 TI - Wear Your Bicycle Helmet! PMID- 27182570 TI - Everything Old is New Again. PMID- 27182571 TI - A CONVERSATION WITH MARILYN TAVENNER. New AHIP Chief Explains What Challenges Lie Ahead. PMID- 27182572 TI - Three Breakthroughs Usher In New Era of Cholesterol Control. PMID- 27182573 TI - [Coalition agrees on flexible management of the mentally ill. Treatment should be in accordance with the latest knowledge]. PMID- 27182574 TI - [White list informs about patient safety and health. Anyone seeking advice should recognize how active individual hospitals are]. PMID- 27182575 TI - [Better assistive devices supply. Coalition plans a "common approach"]. PMID- 27182576 TI - [Moratorium wants to suspend nursing profession law. Reform of nursing professions further heats tempers]. PMID- 27182577 TI - [More independence thanks to technical assistance. Interest in nursing robots is great]. PMID- 27182578 TI - [Baden-Wurttemberg curtails specialist quota. Requests for personnel will be revised]. PMID- 27182579 TI - [Physician must make the patient record completely available. Health insurance complaint against physician]. PMID- 27182580 TI - [Psychiatric nursing: continuing education starts in June]. PMID- 27182581 TI - [Berlin and Brandenburg: uniform regulations for intensive care]. PMID- 27182582 TI - SEQUELAE OF PATIENTS TREATED FOR PULMONARY TUBERCULOSIS IN CHEST CLINIC, TIKUR ANBESSA SPECIALIZED HOSPITAL (TASH), ADDIS ABABA, ETHIOPIA. AB - BACKGROUND: Pulmonary tuberculosis (PTB) is one of the most common infectious diseases worldwide, and contributes significantly to morbidity and mortality in developing countries. Despite availability of effective treatment, a significant number of patients suffer from permanent lung damage, which predisposes patients to numerous pulmonary complications. OBJECTIVE: To assess chronic sequelae of patients treated for PTB in a chest clinic at Tikur Anbessa Hospital. METHODS: This was a retrospective, cross-sectional analysis of patients registered in a clinical database at the chest clinic of Tikur Anbessa specialized Hospital between January and December 2013. Patients with a history of pulmonary tuberculosis treatment were identified and included in the analysis. RESULTS: Among all patients having follow-up at the chest clinic of TASH during the study period, 134 (18.5%) presented with chronic pulmonary complications of TB. Seventy two patients (54%) were male, and the mean and median ages were 40 and 37 years, respectively. Of the study population, 83 (61.9%) patients had clinically significant parenchymal scarring and fibrosis, 40 (29.9%) had bronchiectasis, 5(3.7%) had Aspergilloma, 4(3%) had granuloma/calcification, one patient (0.7%) had pleural thickening, and one patient (0.7%) underwent pneumonectomy during the study period. CONCLUSIONS: Fibrosis and bronchiectasis were the most common pulmonary complications of tuberculosis among patients encountered at the TASH chest clinic during the study period. This demonstrates the impact of pulmonary tuberculosis is beyond management of active disease. PMID- 27182583 TI - HEPATITIS C VIRUS (HCV) SEROPREVALENCE, ANTIGENAEMIA AND ASSOCIATED RISK FACTORS AMONG PREGNANT WOMEN IN NIGERIA. AB - BACKGROUND & AIMS: Hepatitis C viral infection is a significant public health challenge with potential risk of progressing to liver cirrhosis and hepatocellular carcinoma (HCC). Actively infected mothers can transmit the virus to their babies who may develop liver cirrhosis and HCC as young adults. We determined the seroprevalence of HCV, its antigenaemia and associated risk factors among pregnant women. METHODS: We recruited 400 pregnant women and tested their serum for HCV antibodies using immune-chromatographic test and determined the HCV core antigenaemia among HCV sero-positives by enzyme-immunoassay (EIA). The bio-socio-demographic variables of the participants were statistically correlated to the test results. RESULTS: Seroprevalence of HCV was 5.8% (23/400) and the prevalence of HCV core antigenaemia was 73.9% (17/23). None of the bio socio-demographic variables of the participants and other known risk factors evaluated had. significant influence on either seroprevalence of HCV or its antigenaemia. Only the employment status of the participants' husbands (p = 0.01) significantly affected seropositivity of HCV. CONCLUSION: HCV core antigenaemia is high among pregnant women who have antibodies to HCV in our environment and this signifies an active hepatitis C virus infection. PMID- 27182584 TI - PERCEPTION OF FINAL YEAR MEDICAL STUDENTS ABOUT OBJECTIVE STRUCTURED CLINICAL EXAMINATION IN THE DEPARTMENT OF GENERAL SURGERY. AB - Background -Assessment of clinical skills of medical students has a central role in medical education yet the suit- able evaluation methods have persistently debated by educators and students. OBJECTIVES: To assess perceptions of final year medical students about the Organized Structured Clinical Exam (OSCE) METHODS AND MATERIALS: A cross sectional study was performed to assess views of final year medical students who had taken the OSCE in the Department of Surgery of Mekelle University College of Health Sciences, as well as other traditional exam formats in other departments in the medical school. RESULTS: Of the 154 students who took the final qualifying exam, 127 (82.5%) responded to the survey. Eighty four (66%) of the respondents were males. The OSCE was considered as the best assessment method of practical exams by 70 (55.1%) of the respondents, with the conventional long exam next in preference, by 47 (37%) students. For questions addressing the advantages of the OSCE, the average favorability score was between 4.2 - 4.6 out of Likert's type 5-point scale rating. Coverage of common and relevant topics, uniform student assessment, and communication skill assessment were items receiving high favorability scores by a particularly high percentage of students, (96.9%, 95.3% and 70.9% of all students, respectively). CONCLUSIONS: Most of the students favored the OSCE compared to conventional exam styles. Though the study should be confirmed. and extended in other settings, we recommend OSCE to be the main exam type for clinical year surgery examinations. PMID- 27182585 TI - BACTERIOLOGY AND RISK FACTORS OF BACTERIAL KERATITIS IN JIMMA, SOUTHWEST ETHIOPIA. AB - BACKGROUND: In East Africa, particularly in Ethiopia, bacterial keratitis is a major cause of blindness. OBJECTIVE: The aims of this study were to identify risk factors of bacterial keratitis and the spectrum of bacterial etiologies, and to assess the in-vitro antimicrobial susceptibility of these bacterial isolates at Jimma University Specialized Hospital, Southwest Ethiopia. METHODS: A prospective study was employed from January 2012 to June 2012 from which a total of 24 patients with bacterial keratitis were included in the study. Corneal scrapings were collected, transported and microbiologically processed using standard operating procedures. RESULTS: Four different predisposing factors for bacterial keratitis were identified: corneal trauma 9 (37.5%), blepharitis 7 (29.2%), herpetic keratitis, and use of contaminated medications 4. Bilateral corneal infection was found in 5 (20.8%) of the cases. A total of 24 corneal scrapings were collected for microbiological evaluation, of which 20 (83%) had bacterial growth. The isolated bacterial pathogens were Pseudomonas aeruginosa 10 (41.7%), Staphyloccus aureus 5 (20.8%), Serratia marcescens 3 (12.5%), followed by Streptococcus pneumoniae 2 (8.3%). Antimicrobial susceptibility testing revealed that 85% of Gram-negative bacilli were susceptible to gentamicin and ciprofloxacin, while 86% of Gram-positive cocci were susceptible to vancomycin and Ciprofloxacin. CONCLUSIONS: Corneal trauma was the most common risk factor for bacterial keratitis followed by blepharitis. Bacteriological analysis of corneal scrapings also revealed that P. aeruginosa was the most common isolate followed by S. aureus; the antibiotic with the highest susceptibility was ciprofloxacin. As drug resistance among bacterial pathogens is an evolving process, routine surveillance and monitoring studies should be conducted to provide an update and most effective empirical treatment for bacterial keratitis. PMID- 27182586 TI - PATTERNS OF ULTRASOUND FINDINGS IN ABDOMINAL LYMPHOMA PATIENTS AT TIKUR ANBESSA SPECIALIZED HOSPITAL, ADDIS ABABA, ETHIOPIA. AB - BACKGROUND: Malignant lymphoma is a common primary hematopoietic malignancy. Cross sectional imaging is used commonly. The wide spread availability and diagnostic potential of ultrasound (US) place it at the forefront in the setting of resource limited countries that do not have access to the full range of imaging modalities and in which patients frequently present in the late stages of diseases. OBJECTIVE: Assess the patterns of abdominal organ involvement and ultrasound findings in patients with abdominal lymphoma. MATERIAL AND METHODS: 69 consecutive patients who came to the US unit of Tikur Anbessa Specialized Hospital (TASH) with the diagnosis of lymphoma were scanned. All examinations were performed by the authors based on standard scanning techniques. Cine and spot images were stored for analysis and finding recorded on a preprepared and pretested format. RESULTS: Eighty nine percent of the patients were below the age of 60 and 75% were males. Chest x-ray and US were the modalities commonly used, while only 6 of 69 had computed tomography (CT) scans. Non-Hodgkin's lymphoma account for 81% of the cases. Lymph nodes were the most common organ involved and abdominal nodes accounted for 61% of the cases. Homogenous and hypoechoic echo appearances were seen in 52% and their pattern of involvement comprised multiple discrete nodes. Comparable overall patterns of involvement were seen in both pathologically confirmed and unconfirmed lymphoma cases. Liver followed by spleen was the most common abdominal organ involved, and organ enlargement and/or multiple variable sized hypoechoic lesions were the most common US findings. CONCLUSION: Our study emphasizes the continued role of US for lymphoma patients. The US findings and pattern of organ involvement was found to be comparable with previous studies. PMID- 27182587 TI - FOREIGN BODY INDUCED TRACHEOESOPHAGEAL FISTULA IN A PEDIATRIC PATIENT WITH A MISDIAGNOSIS: CASE REPORT AND REVIEW OF LITERATURE. AB - Acquired tracheoesophageal fistulae can be diagnosed clinically by features such as cough elicited by swallowing but symptoms can be mild. Here, we report a case of a foreign body induced trachea-esophageal fistula in a 2 year and 6 months old male child with a chronic cough who had long been misdiagnosed and mismanaged. PMID- 27182588 TI - DYSKERATOSIS CONGENITA IN TWO ETHIOPIAN BROTHERS. AB - Dyskeratosis congenita (DKC) is a rare, progressive bone marrow failure syndrome that is characterized by the triad of reticulated skin pigmentation, nail dystrophy and oral leukoplakia. Current evidence indicates that DKC is a disease of defective telomere maintenance, ribosome deficiency and protein synthesis dysfunction. Mortality is often associated with bone marrow failure (BMF), development of malignancy and other multisystem complications of the disease. Here we report two Ethiopian brothers with classical signs and symptoms of DKC. The characteristic clinical features, laboratory findings, and clinical course of the two brothers are discussed along with relevant literature review. PMID- 27182589 TI - Publisher's Note: Phenomenological Blasius-type friction equation for turbulent power-law fluid flows [Phys. Rev. E 92, 063006 (2015)]. AB - This corrects the article DOI: 10.1103/PhysRevE.92.063006. PMID- 27182590 TI - Erratum: Torque correlation length and stochastic twist dynamics of DNA [Phys. Rev. E 89, 062706 (2014)]. AB - This corrects the article DOI: 10.1103/PhysRevE.89.062706. PMID- 27182591 TI - Publisher's Note: Translocation of a semiflexible polymer through a nanopore in the presence of attractive binding particles [Phys. Rev. E 92, 032711 (2015)]. AB - This corrects the article DOI: 10.1103/PhysRevE.92.032711. PMID- 27182592 TI - Publisher's Note: Loading-unloading hysteresis loop of randomly rough adhesive contacts [Phys. Rev. E 92, 062404 (2015)]. AB - This corrects the article DOI: 10.1103/PhysRevE.92.062404. PMID- 27182593 TI - Publisher's Note: Defining the free-energy landscape of curvature-inducing proteins on membrane bilayers [Phys. Rev. E 90, 022717 (2014)]. AB - This corrects the article DOI: 10.1103/PhysRevE.90.022717. PMID- 27182595 TI - Effects of Electrodeposition Mode and Deposition Cycle on the Electrochemical Performance of MnO2-NiO Composite Electrodes for High-Energy-Density Supercapacitors. AB - Nanostructured network-like MnO2-NiO composite electrodes were electrodeposited onto stainless steel substrates via different electrodeposition modes, such as chronopotentiometry, chronoamperometry, and cyclic voltammetry, and then subjected to heat treatment at 300 degrees C for metal oxide conversion. X-ray diffraction, field emission scanning electron microscopy, and transmission electron microscopy were used to study the crystalline natures and morphologies of the deposited films. The electrochemical properties were investigated using cyclic voltammetry and charge/discharge tests. The results revealed that the electrochemical performance of the as-obtained composite electrodes depended on the electrodeposition mode. The electrochemical properties of MnO2-NiO composite electrodes prepared using cyclic voltammetry exhibited the highest capacitance values and were most influenced by the deposition cycle number. The optimum specific capacitance was 3509 Fg-1 with energy and power densities of 1322 Wh kg 1 and 110.5 kW kg-1, respectively, at a current density of 20 Ag-1 in a mixed KOH/K3Fe(CN)6 electrolyte. PMID- 27182594 TI - Transcriptome Sequencing of Chemically Induced Aquilaria sinensis to Identify Genes Related to Agarwood Formation. AB - BACKGROUND: Agarwood is a traditional Chinese medicine used as a clinical sedative, carminative, and antiemetic drug. Agarwood is formed in Aquilaria sinensis when A. sinensis trees are threatened by external physical, chemical injury or endophytic fungal irritation. However, the mechanism of agarwood formation via chemical induction remains unclear. In this study, we characterized the transcriptome of different parts of a chemically induced A. sinensis trunk sample with agarwood. The Illumina sequencing platform was used to identify the genes involved in agarwood formation. METHODOLOGY/PRINCIPAL FINDINGS: A five-year old Aquilaria sinensis treated by formic acid was selected. The white wood part (B1 sample), the transition part between agarwood and white wood (W2 sample), the agarwood part (J3 sample), and the rotten wood part (F5 sample) were collected for transcriptome sequencing. Accordingly, 54,685,634 clean reads, which were assembled into 83,467 unigenes, were obtained with a Q20 value of 97.5%. A total of 50,565 unigenes were annotated using the Nr, Nt, SWISS-PROT, KEGG, COG, and GO databases. In particular, 171,331,352 unigenes were annotated by various pathways, including the sesquiterpenoid (ko00909) and plant-pathogen interaction (ko03040) pathways. These pathways were related to sesquiterpenoid biosynthesis and defensive responses to chemical stimulation. CONCLUSIONS/SIGNIFICANCE: The transcriptome data of the different parts of the chemically induced A. sinensis trunk provide a rich source of materials for discovering and identifying the genes involved in sesquiterpenoid production and in defensive responses to chemical stimulation. This study is the first to use de novo sequencing and transcriptome assembly for different parts of chemically induced A. sinensis. Results demonstrate that the sesquiterpenoid biosynthesis pathway and WRKY transcription factor play important roles in agarwood formation via chemical induction. The comparative analysis of the transcriptome data of agarwood and A. sinensis lays the foundation for elucidating the mechanism of agarwood formation via chemical induction, and thus, enables future improvements in agarwood quality while protecting endangered wild A. sinensis. PMID- 27182596 TI - Effects of Dispersal and Initial Diversity on the Composition and Functional Performance of Bacterial Communities. AB - Natural communities are open systems and consequently dispersal can play an important role for the diversity, composition and functioning of communities at the local scale. It is, however, still unclear how effects of dispersal differ depending on the initial diversity of local communities. Here we implemented an experiment where we manipulated the initial diversity of natural freshwater bacterioplankton communities using a dilution-to-extinction approach as well as dispersal from a regional species pool. The aim was further to test whether dispersal effects on bacterial abundance and functional parameters (average community growth rates, respiration rates, substrate utilisation ability) differ in dependence of the initial diversity of the communities. First of all, we found that both initial diversity and dispersal rates had an effect on the recruitment of taxa from a regional source, which was higher in communities with low initial diversity and at higher rates of dispersal. Higher initial diversity and dispersal also promoted higher levels of richness and evenness in local communities and affected, both, separately or interactively, the functional performance of communities. Our study therefore suggests that dispersal can influence the diversity, composition and functioning of bacterial communities and that this effect may be enhanced if the initial diversity of communities is depleted. PMID- 27182598 TI - Herbivore Diet Breadth and Host Plant Defense Mediate the Tri-Trophic Effects of Plant Toxins on Multiple Coccinellid Predators. AB - Host plant defenses are known to cascade up food chains to influence herbivores and their natural enemies, but how herbivore and predator traits and identity mediate such tri-trophic dynamics is largely unknown. We assessed the influence of plant defense on aphid and coccinellid performance in laboratory trials with low- vs. high-glucosinolate varieties of Brassica napus, a dietary specialist (Brevicoryne brassicae) and generalist (Myzus persicae) aphid, and five species of aphidophagous coccinellids. The performance of the specialist and generalist aphids was similar and unaffected by variation in plant defense. Aphid glucosinolate concentration and resistance to predators differed by aphid species and host plant defense, and these effects acted independently. With respect to aphid species, the dietary generalist aphid (vs. specialist) had 14% lower glucosinolate concentration and coccinellid predators ate three-fold more aphids. With respect to host plant variety, the high-glucosinolate plants (vs. low) increased aphid glucosinolate concentration by 21%, but had relatively weak effects on predation by coccinellids and these effects varied among coccinellid species. In turn, coccinellid performance was influenced by the interactive effects of plant defense and aphid species, as the cascading, indirect effect of plant defense was greater when feeding upon the specialist than generalist aphid. When feeding upon specialist aphids, low- (vs. high-) glucosinolate plants increased coccinellid mass gain by 78% and accelerated development by 14%. In contrast, when feeding upon generalist aphids, low- (vs. high-) glucosinolate plants increased coccinellid mass gain by only 11% and had no detectable effect on development time. These interactive effects of plant defense and aphid diet breadth on predator performance also varied among coccinellid species; the indirect negative effects of plant defenses on predator performance was consistent among the five predators when transmitted via the dietary specialist aphid, but these effects varied substantially among predators-in both the magnitude and direction-when transmitted via the dietary generalist aphid. Accordingly, the cascading effect of plant defense on predators was stronger in magnitude and more consistent among predator taxa when transmitted by the specialist than generalist herbivore. Overall, these findings support a central role of herbivore diet breadth in mediating both the strength and contingency of tri-trophic interactions. PMID- 27182597 TI - An Antibody Screen of a Plasmodium vivax Antigen Library Identifies Novel Merozoite Proteins Associated with Clinical Protection. AB - BACKGROUND: Elimination of Plasmodium vivax malaria would be greatly facilitated by the development of an effective vaccine. A comprehensive and systematic characterization of antibodies to P. vivax antigens in exposed populations is useful in guiding rational vaccine design. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we investigated antibodies to a large library of P. vivax entire ectodomain merozoite proteins in 2 Asia-Pacific populations, analysing the relationship of antibody levels with markers of current and cumulative malaria exposure, and socioeconomic and clinical indicators. 29 antigenic targets of natural immunity were identified. Of these, 12 highly-immunogenic proteins were strongly associated with age and thus cumulative lifetime exposure in Solomon Islanders (P<0.001-0.027). A subset of 6 proteins, selected on the basis of immunogenicity and expression levels, were used to examine antibody levels in plasma samples from a population of young Papua New Guinean children with well characterized individual differences in exposure. This analysis identified a strong association between reduced risk of clinical disease and antibody levels to P12, P41, and a novel hypothetical protein that has not previously been studied, PVX_081550 (IRR 0.46-0.74; P<0.001-0.041). CONCLUSION/SIGNIFICANCE: These data emphasize the benefits of an unbiased screening approach in identifying novel vaccine candidate antigens. Functional studies are now required to establish whether PVX_081550 is a key component of the naturally-acquired protective immune response, a biomarker of immune status, or both. PMID- 27182599 TI - Missing Rings, Synchronous Growth, and Ecological Disturbance in a 36-Year Pitch Pine (Pinus rigida) Provenance Study. AB - Provenance studies are an increasingly important analog for understanding how trees adapted to particular climatic conditions might respond to climate change. Dendrochronological analysis can illuminate differences among trees from different seed sources in terms of absolute annual growth and sensitivity to external growth factors. We analyzed annual radial growth of 567 36-year-old pitch pine (Pinus rigida Mill.) trees from 27 seed sources to evaluate their performance in a New Jersey Pine Barrens provenance experiment. Unexpectedly, missing rings were prevalent in most trees, and some years-1992, 1999, and 2006 had a particularly high frequency of missing rings across the plantation. Trees from local seed sources (<55 km away from the plantation) had a significantly smaller percentage of missing rings from 1980-2009 (mean: 5.0%), relative to northernmost and southernmost sources (mean: 9.3% and 7.9%, respectively). Some years with a high frequency of missing rings coincide with outbreaks of defoliating insects or dry growing season conditions. The propensity for missing rings synchronized annual variations in growth across all trees and might have complicated the detection of potential differences in interannual variability among seed sources. Average ring width was significantly larger in seed sources from both the southernmost and warmest origins compared to the northernmost and coldest seed sources in most years. Local seed sources had the highest average radial growth. Adaptation to local environmental conditions and disturbances might have influenced the higher growth rate found in local seed sources. These findings underscore the need to understand the integrative impact of multiple environmental drivers, such as disturbance agents and climate change, on tree growth, forest dynamics, and the carbon cycle. PMID- 27182600 TI - Cyclic AMP Receptor Protein Acts as a Transcription Regulator in Response to Stresses in Deinococcus radiodurans. AB - The cyclic AMP receptor protein family of transcription factors regulates various metabolic pathways in bacteria, and also play roles in response to environmental changes. Here, we identify four homologs of the CRP family in Deinococcus radiodurans, one of which tolerates extremely high levels of oxidative stress and DNA-damaging reagents. Transcriptional levels of CRP were increased under hydrogen peroxide (H2O2) treatment during the stationary growth phase, indicating that CRPs function in response to oxidative stress. By constructing all CRP single knockout mutants, we found that the dr0997 mutant showed the lowest tolerance toward H2O2, ultraviolet radiation, ionizing radiation, and mitomycin C, while the phenotypes of the dr2362, dr0834, and dr1646 mutants showed slight or no significant differences from those of the wild-type strain. Taking advantage of the conservation of the CRP-binding site in many bacteria, we found that transcription of 18 genes, including genes encoding chromosome-partitioning protein (dr0998), Lon proteases (dr0349 and dr1974), NADH-quinone oxidoreductase (dr1506), thiosulfate sulfurtransferase (dr2531), the DNA repair protein UvsE (dr1819), PprA (dra0346), and RecN (dr1447), are directly regulated by DR0997. Quantitative real-time polymerase chain reaction (qRT-PCR) analyses showed that certain genes involved in anti-oxidative responses, DNA repair, and various cellular pathways are transcriptionally attenuated in the dr0997 mutant. Interestingly, DR0997 also regulate the transcriptional levels of all CRP genes in this bacterium. These data suggest that DR0997 contributes to the extreme stress resistance of D. radiodurans via its regulatory role in multiple cellular pathways, such as anti-oxidation and DNA repair pathways. PMID- 27182602 TI - A New Bioinspired Perchlorate Reduction Catalyst with Significantly Enhanced Stability via Rational Tuning of Rhenium Coordination Chemistry and Heterogeneous Reaction Pathway. AB - Rapid reduction of aqueous ClO4(-) to Cl(-) by H2 has been realized by a heterogeneous Re(hoz)2-Pd/C catalyst integrating Re(O)(hoz)2Cl complex (hoz = oxazolinyl-phenolato bidentate ligand) and Pd nanoparticles on carbon support, but ClOx(-) intermediates formed during reactions with concentrated ClO4(-) promote irreversible Re complex decomposition and catalyst deactivation. The original catalyst design mimics the microbial ClO4(-) reductase, which integrates Mo(MGD)2 complex (MGD = molybdopterin guanine dinucleotide) for oxygen atom transfer (OAT). Perchlorate-reducing microorganisms employ a separate enzyme, chlorite dismutase, to prevent accumulation of the destructive ClO2(-) intermediate. The structural intricacy of MGD ligand and the two-enzyme mechanism for microbial ClO4(-) reduction inspired us to improve catalyst stability by rationally tuning Re ligand structure and adding a ClOx(-) scavenger. Two new Re complexes, Re(O)(htz)2Cl and Re(O)(hoz)(htz)Cl (htz = thiazolinyl-phenolato bidentate ligand), significantly mitigate Re complex decomposition by slightly lowering the OAT activity when immobilized in Pd/C. Further stability enhancement is then obtained by switching the nanoparticles from Pd to Rh, which exhibits high reactivity with ClOx(-) intermediates and thus prevents their deactivating reaction with the Re complex. Compared to Re(hoz)2-Pd/C, the new Re(hoz)(htz) Rh/C catalyst exhibits similar ClO4(-) reduction activity but superior stability, evidenced by a decrease of Re leaching from 37% to 0.25% and stability of surface Re speciation following the treatment of a concentrated "challenge" solution containing 1000 ppm of ClO4(-). This work demonstrates the pivotal roles of coordination chemistry control and tuning of individual catalyst components for achieving both high activity and stability in environmental catalyst applications. PMID- 27182603 TI - Serum Folate Shows an Inverse Association with Blood Pressure in a Cohort of Chinese Women of Childbearing Age: A Cross-Sectional Study. AB - BACKGROUND: It has been reported that higher folate intake from food and supplementation is associated with decreased blood pressure (BP). The association between serum folate concentration and BP has been examined in few studies. We aim to examine the association between serum folate and BP levels in a cohort of young Chinese women. METHODS: We used the baseline data from a pre-conception cohort of women of childbearing age in Liuyang, China, for this study. Demographic data were collected by structured interview. Serum folate concentration was measured by immunoassay, and homocysteine, blood glucose, triglyceride and total cholesterol were measured through standardized clinical procedures. Multiple linear regression and principal component regression model were applied in the analysis. RESULTS: A total of 1,532 healthy normotensive non pregnant women were included in the final analysis. The mean concentration of serum folate was 7.5 +/- 5.4 nmol/L and 55% of the women presented with folate deficiency (< 6.8 nmol/L). Multiple linear regression and principal component regression showed that serum folate levels were inversely associated with systolic and diastolic BP, after adjusting for demographic, anthropometric, and biochemical factors. CONCLUSIONS: Serum folate is inversely associated with BP in non-pregnant women of childbearing age with high prevalence of folate deficiency. PMID- 27182601 TI - Utilizing a TLR5-Adjuvanted Cytomegalovirus as a Lentiviral Vaccine in the Nonhuman Primate Model for AIDS. AB - Despite tremendous progress in our understanding of human immunodeficiency virus (HIV) natural history and advances in HIV treatment, there is neither an approved vaccine nor a cure for infection. Here, we describe the development and characterization of a novel replicating vaccine vector utilizing Cytomegalovirus (CMV) and a TLR5 adjuvant. After partial truncation of the central, immunodominant hypervariable domain, flagellin (fliC) from Salmonella was cloned downstream of a codon optimized gag gene from simian immunodeficiency virus (SIV) and transiently expressed in telomerized rhesus fibroblast (TeloRF) cells in culture. Lysates generated from these transfected cells induced the tumor necrosis factor alpha (TNF-alpha), in a mouse macrophage cell line, in a TLR5 dependent manner. The Gag/FliC expression construct was cloned into a bacterial artificial chromosome encoding the rhesus CMV (RhCMV) genome, and infectious RhCMV was generated following transfection of TeloRF cells. This virus stably expressed an SIV Gag/FliC fusion protein through four serial passages. Lysates generated from infected cells induced TNF-alpha in a TLR5-dependent manner. Western blot analysis of infected cell lysates verified expression of a Gag/FliC fusion protein using a SIV p27 capsid monoclonal antibody. Lastly, rhesus macaques inoculated with this novel RhCMV virus demonstrated increased inflammatory responses at the site of inoculation seven days post-infection when compared to the parental RhCMV. These results demonstrate that an artificially constructed replicating RhCMV expressing an SIV Gag/FliC fusion protein is capable of activating TLR5 in a macrophage cell line in vitro and induction of an altered inflammatory response in vivo. Ongoing animals studies are aimed at determining vaccine efficacy, including subsequent challenge with pathogenic SIV. PMID- 27182604 TI - The Status of Honey Bee Health in Italy: Results from the Nationwide Bee Monitoring Network. AB - In Italy a nation-wide monitoring network was established in 2009 in response to significant honey bee colony mortality reported during 2008. The network comprised of approximately 100 apiaries located across Italy. Colonies were sampled four times per year, in order to assess the health status and to collect samples for pathogen, chemical and pollen analyses. The prevalence of Nosema ceranae ranged, on average, from 47-69% in 2009 and from 30-60% in 2010, with strong seasonal variation. Virus prevalence was higher in 2010 than in 2009. The most widespread viruses were BQCV, DWV and SBV. The most frequent pesticides in all hive contents were organophosphates and pyrethroids such as coumaphos and tau fluvalinate. Beeswax was the most frequently contaminated hive product, with 40% of samples positive and 13% having multiple residues, while 27% of bee-bread and 12% of honey bee samples were contaminated. Colony losses in 2009/10 were on average 19%, with no major differences between regions of Italy. In 2009, the presence of DWV in autumn was positively correlated with colony losses. Similarly, hive mortality was higher in BQCV infected colonies in the first and second visits of the year. In 2010, colony losses were significantly related to the presence of pesticides in honey bees during the second sampling period. Honey bee exposure to poisons in spring could have a negative impact at the colony level, contributing to increase colony mortality during the beekeeping season. In both 2009 and 2010, colony mortality rates were positively related to the percentage of agricultural land surrounding apiaries, supporting the importance of land use for honey bee health. PMID- 27182606 TI - Solution-Processable BODIPY-Based Small Molecules for Semiconducting Microfibers in Organic Thin-Film Transistors. AB - Electron-deficient pi-conjugated small molecules can function as electron transporting semiconductors in various optoelectronic applications. Despite their unique structural, optical, and electronic properties, the development of BODIPY based organic semiconductors has lagged behind that of other pi-deficient units. Here, we report the design and synthesis of two novel solution-proccessable BODIPY-based small molecules (BDY-3T-BDY and BDY-4T-BDY) for organic thin-film transistors (OTFTs). The new semiconductors were fully characterized by (1)H/(13)C NMR, mass spectrometry, cyclic voltammetry, UV-vis spectroscopy, photoluminescence, differential scanning calorimetry, and thermogravimetric analysis. The single-crystal X-ray diffraction (XRD) characterization of a key intermediate reveals crucial structural properties. Solution-sheared top contact/bottom-gate OTFTs exhibited electron mobilities up to 0.01 cm(2)/V.s and current on/off ratios of >10(8). Film microstructural and morphological characterizations indicate the formation of relatively long (~0.1 mm) and micrometer-sized (1-2 MUm) crystalline fibers for BDY-4T-BDY-based films along the shearing direction. Fiber-alignment-induced charge-transport anisotropy (MU?/MU? ~ 10) was observed, and higher mobilities were achieved when the microfibers were aligned along the conduction channel, which allows for efficient long-range charge-transport between source and drain electrodes. These OTFT performances are the highest reported to date for a BODIPY-based molecular semiconductor, and demonstrate that BODIPY is a promising building block for enabling solution-processed, electron-transporting semiconductor films. PMID- 27182605 TI - Human RPE Stem Cell-Derived RPE Preserves Photoreceptors in the Royal College of Surgeons Rat: Method for Quantifying the Area of Photoreceptor Sparing. AB - PURPOSE: Numerous preclinical studies have shown that transplantation of stem cell-derived retinal pigment epithelial cell (RPE) preserves photoreceptor cell anatomy in the dystrophic Royal College of Surgeons (RCS) rat. How rescue is spatially distributed over the eye, relative to the transplantation site, is less clear. To understand spatial variations in transplant efficacy, we have developed a method to measure the spatial distribution of rescued photoreceptor cells. METHODS: Human RPE Stem Cell-derived RPE (RPESC-RPE) cells were subretinally injected into RCS rat eyes. After tissue recovery and orientating the globe, a series of retinal sections were cut through the injected area. Sections were stained with DAPI (4',6-diamidino-2-phenylindole) and a number of photoreceptor nuclei were counted across the nasal-temporal and superior-inferior axes. These data were used to construct 2D maps of the area of photoreceptor cell saving. RESULTS: Photoreceptor cell preservation was detected in the injected temporal hemisphere and occupied areas greater than 4 mm(2) centered near the injection sites. Rescue was directed toward the central retina and superior and inferior poles, with maximal number of rescued photoreceptor cells proximal to the injection sites. CONCLUSIONS: RPESC-RPE transplantation preserves RCS photoreceptor cells. The photoreceptor cell contour maps readily convey the extent of rescue across the eye. The consistent alignment and quantification of results using this method allow the application of other downstream statistical analyses and comparisons to better understand transplantation therapy in the eye. PMID- 27182607 TI - Validation of a Food Frequency Questionnaire for Bone Nutrients in Pregnant Women. AB - PURPOSE: The aim was to validate a food frequency questionnaire (FFQ) against a 3 day food record (3DFR) for pregnant women with a focus on nutrients important for bone health from food and supplements. METHODS: The FFQ and 3DFR were administered to pregnant women (n = 42) aged 18-45 years in their third trimester of pregnancy in Hamilton, Ontario. Nutrient analysis of intakes was conducted using an FFQ calculator and Nutritionist-Pro software. The average daily serving consumption of Milk and alternatives group and Vegetable subgroup from Canada's Food Guide were also compared. RESULTS: There was a high positive correlation between methods for total dietary vitamin D (r = 0.83). Low positive associations were observed for total protein (r = 0.37), calcium (r = 0.36), vitamin K (r = 0.41), and servings of Milk and alternatives (r = 0.36). A cross-classification analysis using participants' intake quartiles revealed no major misclassifications. Bland-Altman analysis showed that the FFQ mildly underestimated the intake for protein, whereas it grossly overestimated the intake of vitamin K, and daily servings of Milk and alternatives and Vegetable. CONCLUSIONS: This FFQ can serve as a useful tool in clinical and research settings to assess key bone nutrients from foods and supplement sources in pregnant women. PMID- 27182608 TI - Citrus flavanones prevent systemic inflammation and ameliorate oxidative stress in C57BL/6J mice fed high-fat diet. AB - The flavanones hesperidin, eriocitrin and eriodictyol were investigated for their prevention of the oxidative stress and systemic inflammation caused by high-fat diet in C57BL/6J mice. The mice received a standard diet (9.5% kcal from fat), high-fat diet (45% kcal from fat) or high-fat diet supplemented with hesperidin, eriocitrin or eriodictyol for a period of four weeks. Hesperidin, eriocitrin and eriodictyol increased the serum total antioxidant capacity, and restrained the elevation of interleukin-6 (IL-6), macrophage chemoattractant protein-1 (MCP-1), and C-reactive protein (hs-CRP). In addition, the liver TBARS levels and spleen mass (g per kg body weight) were lower for the flavanone-treated mice than in the unsupplemented mice. Eriocitrin and eriodictyol reduced TBARS levels in the blood serum, and hesperidin and eriodictyol also reduced fat accumulation and liver damage. The results showed that hesperidin, eriocitrin and eriodictyol had protective effects against inflammation and oxidative stress caused by high-fat diet in mice, and may therefore prevent metabolic alterations associated with the development of cardiovascular diseases in other animals. PMID- 27182609 TI - Synthesis and Structure of Corona[6](het)arenes Containing Mixed Bridge Units. AB - A one-pot nucleophilic aromatic substitution reaction of 3,6-dichlorotetrazine with various diphenols and dibenzenethiols produced corona[4]arene[2]tetrazines that contain mixed oxygen, sulfide, methylene, and sulfone linkages. Macrocyclic ring transformations employing an inverse-electron-demand Diels-Alder reaction of tetrazine moieties with enamines and the subsequent sulfide oxidation reaction afforded diverse corona[4]arene[2]pyridazines. The acquired corona[6]arenes adopted three types of conformational structures in the crystalline state. PMID- 27182610 TI - Serum cystatin C and neutrophil gelatinase-associated lipocalin in predicting the severity of coronary artery disease in diabetic patients. AB - OBJECTIVE: Cystatin C and neutrophil gelatinase-associated lipocalin (NGAL) are biomarkers of renal functions. We evaluated their roles in predicting the severity of coronary artery disease (CAD). METHODS: Fifty-two consecutive type 2 diabetic patients (32 males, 65.7+/-8.6 years) who underwent coronary angiography (CAG) for stable CAD were included in this single-center, prospective, cross sectional study. Patients with an estimated glomerular filtration rate <60 mL/min/1.73 m2 and with a history of by-pass surgery and/or coronary stent implantation were excluded. The vessel score and Gensini score were calculated to assess the presence and severity of CAD. Mann-Whitney U test, Spearman test, and multiple linear regression analysis were used for the main statistical analyses. RESULTS: Serum cystatin C levels were higher in patients with multivessel disease than in those with single vessel disease [1260 ng/mL (953-1640) vs. 977 ng/mL (599-1114), p=0.017]. According to the median Gensini score, the higher score group also had higher cystatin C levels than the lower score group [1114 ng/mL (948-1567) vs. 929 ng/mL (569-1156), p=0.009]. However, serum NGAL levels were similar between these subgroups. There was a positive correlation between cystatin C and Gensini score (r=0.334, p=0.016). Multiple linear regression analysis revealed serum cystatin C as an independent predictor of the Gensini score (beta=0.360, t=2.311, p=0.026). These results may aid in defining cystatin C as a surrogate marker of the extent of CAD in further clinical trials. CONCLUSION: Serum Cystatin C, but not NGAL levels, could predict the severity of CAD in diabetic patients. PMID- 27182611 TI - Association between central aortic pulsatility and glomerular filtration rate in patients with coronary artery disease. AB - OBJECTIVE: Aortic stiffness and chronic kidney disease share common risk factors. Increased aortic stiffness is a predictor of lower estimated glomerular filtration rate (eGFR) at lower levels of renal functions. We aimed to investigate the association between invasively measured central aortic pulsatility (AP) as an indicator of aortic stiffness and eGFR in a population with coronary artery disease and without overt renal disease. METHODS: This study had a cross-sectional design. Data were retrospectively collected. We evaluated 72 patients (44 males and 28 females; mean age 59.0+/-10.3 years) with coronary artery disease. eGFR was calculated with dividing the Cockcroft-Gault formula by body surface area. Direct measurements of aortic blood pressures were utilized to calculate pulse pressure and AP. Multiple linear regression analysis was performed to test the relationship between eGFR and AP, independent from potential confounders. RESULTS: eGFR was significantly correlated with age (r=0.489, p<0.001), body surface area (r=0.324, p=0.006), weight (r=0.323, p=0.006), aortic pulse pressure (r=-0.371, p=0.001), and AP (r=-0.469, p<0.001). In multiple linear regression analysis, AP was independently associated with eGFR (p=0.035), beside the age and body surface area. An AP cut-off level of >0.71 had 84% sensitivity and 72% specificity in predicting eGFR of <90 mL/min per 1.72 m2 (receiver-operating characteristic area under curve: 0.851, 95% CI: 0.760-0.942, p<0.001). CONCLUSION: We found an independent relationship between invasively measured AP and eGFR in patients with coronary artery disease. Moreover, a higher AP may predict lower eGFR. These results may be utilized to predict eGFR from AP during invasive procedures. PMID- 27182612 TI - Matrix metalloproteinases are possible targets in monocrotaline-induced pulmonary hypertension: investigation of anti-remodeling effects of alagebrium and everolimus. AB - OBJECTIVE: In our study, sildenafil alone and everolimus or alagebrium in combination with sildenafil were investigated in terms of their additional therapeutic and anti-remodeling activity in monocrotaline-induced pulmonary hypertension (PH) model in rats. In particular, the inter-relationships between PH and matrix metalloproteinases (MMPs) were investigated. METHODS: The pulmonary artery responses of male Sprague Dawley rats were recorded using myography, and the quantities and activities of MMPs were analyzed in homogenates of the pulmonary arteries and lungs by enzyme-linked immunosorbent assays, activity assays, and gelatin zymography techniques. RESULTS: Our results indicated that the therapeutic effects of sildenafil were accompanied by its suppressor effects on MMP activity. It was also shown that everolimus or alagebrium in combination with sildenafil showed additional regulatory effects on MMPs as well as functional responses on pulmonary artery pressure. Therefore, the enzymes in the MMP superfamily are likely to be target molecules for the treatment of PH. CONCLUSION: In conclusion, MMPs were involved in the pathogenesis of PH, and our results suggested that the addition of everolimus or alagebrium to sildenafil therapy may be beneficial in PH. Our results indicated that agents that limit pulmonary vascular hypertrophy and inflammation via their anti-remodeling effects significantly ameliorate mortality and morbidity in PH. PMID- 27182613 TI - The role of oxidative DNA damage and GSTM1, GSTT1, and hOGG1 gene polymorphisms in coronary artery disease risk. AB - OBJECTIVE: Atherosclerotic coronary artery disease (CAD) appears to be a multifactorial process caused by the interaction of environmental risk factors with multiple predisposing genes. Therefore, in this study we aimed to determine the role of oxidative DNA damage and some variations in glutathione S-transferase (GSTM1 and GSTT1) and DNA repair (hOGG1) genes in CAD risk. METHODS: A case control study was conducted on 59 individuals who had undergone coronary angiographic evaluation. Of these, 29 were patients diagnosed with CAD (mean age =61.5+/-10.3) and 30 were controls examined for reasons other than suspected CAD and who had angiographically documented normal coronary arteries (mean age =60.4+/-11.6). Basal DNA damage as well as pyrimidine and purine base damage were evaluated in peripheral blood lymphocytes using the modified comet assay. Polymerase chain reaction-restriction length polymorphism (PCR-RFLP)-based assay was used for genotyping. RESULTS: Basal DNA damage levels in patients [9.16 (3.26)] were significantly higher than those in controls [7.59 (3.23); p=0.017], and basal DNA and pyrimidine base damage levels were significantly correlated with disease severity based on Gensini scoring (r=0.352, p=0.006; r=0.318, p=0.014, respectively). However, no significant differences were observed in terms of oxidized DNA bases between patients and controls. The frequencies of studied genotypes (GSTM1, GSTT1, and hOGG1) were similar between groups. CONCLUSION: The results of this study pointed out the role of DNA damage in CAD and its severity. However, GSTM1, GSTT1, and hOGG1 gene polymorphisms seemed to have no effect on individual susceptibility for disease progression. PMID- 27182614 TI - High fructose diet suppresses exercise-induced increase in AQP7 expression in the in vivo rat heart. AB - OBJECTIVE: Cardiac uptake of fructose is thought to be mediated by glucose transporter 5 (GLUT5), whereas the uptake of glycerol is facilitated by aquaporin 7 (AQP7). We aimed to investigate the effect of a high-fructose diet (HFD) on GLUT5 and AQP7 levels in the rat heart subjected to exercise. METHODS: Male Sprague-Dawley rats were allocated to control (C; n=11), exercise (E; n=10), HFD (n=12), and HFD plus exercise (HFD-E; n=12) groups. HFD was started 28 days before euthanasia. From day 24 to 27, rats were subjected to moderate exercise, followed by vigorous exercise on day 28 (groups E and HFD-E). Cardiac GLUT5 and AQP7 mRNA levels were determined using RT-PCR. The protein contents of GLUT5 and AQP7 were immunohistochemically assessed. Paired-t, ANOVA with Bonferroni, Kruskal-Wallis, and Bonferroni-corrected Mann-Whitney U tests were used for statistical analysis. RESULTS: GLUT5 mRNA expression and protein content did not differ between the groups. AQP7 mRNA levels significantly increased (4.8-fold) in group E compared with in group C (p<0.001). Compared with group C, no significant change was observed in AQP7 mRNA levels in groups HFD and HFD-E. The AQP7 staining score in group E was significantly higher than that in groups C (p<0.001), E (p<0.001), and HFD-E (p<0.001). CONCLUSION: Our study indicates that exercise enhances cardiac AQP7 mRNA expression and protein content. However, HFD prevents the exercise-induced increase in cardiac AQP7 expression. This inhibitory effect may be related to the competition between fructose and glycerol as energy substrates in the rat heart subjected to 5 days of physical exercise. PMID- 27182615 TI - Myocardial infarction as a thrombotic complication of essential thrombocythemia and polycythemia vera. AB - OBJECTIVE: Detailed analyses of clinical characteristics of myocardial infarction (MI) as an essential thrombocythemia (ET)- and polycythemia vera (PV)-related complication have been so far presented mostly as case reports. Therefore, the aim of this retrospective analysis was to evaluate the main cardiological and hematological characteristics for better understanding myocardial complications in ET/PV. METHODS: A retrospective analysis was carried out involving 263 patients diagnosed with ET or PV (155/108) between 1998 and 2014. Fourteen patients suffered MI during the hematological follow-up. Their clinical characteristics were compared to 162 patients (97 ET and 65 PV patients) who did not exhibit any major thrombotic complications (MI, stroke/transient ischemic attack, and venous events) before or after hematological diagnosis of ET/PV. RESULTS: Fourteen MI events occurred among the 263 patients (5.3%). Vascular risk factors were found in 92.9% (13/14) of analyzed cases. In all, 71.4% of the MI complications developed within 12 months after the diagnosis of ET/PV. The coronary angiography findings revealed ST-elevation MI in four cases and non-ST elevation MI in 10. Significant stenosis of coronary arteries requiring percutaneous coronary intervention with a stent implantation was present in seven cases, while three had complex stenoses or previous grafts/stents. All of them had undergone coronary artery bypass graft operations. CONCLUSION: The results of the present study suggest that early detection and consideration of individual management of vascular risk factors in ET/PV patients are also important. Furthermore, a better theoretic understanding of platelet activation and role of leukocytes in myeloproliferative neoplasm-related thrombosis could open new perspectives in thrombosis prediction and prevention. PMID- 27182616 TI - The effect of CYP2C9 and VKORC1 genetic polymorphisms on warfarin dose requirements in a pediatric population. AB - OBJECTIVE: The aim was to investigate the frequency of genetic polymorphisms of cytochrome P4502C9 (CYP2C9) and vitamin K epoxide reductase complex subunit1 (VKORC1) and determine the effect of these polymorphisms on warfarin dose requirements in pediatric patients. METHODS: Fifty-eight pediatric patients with cardiac disease, thrombophilia, or other conditions, taking a stable warfarin dose, aged 0.2-18 years, and with international normalized ratio (INR) between 2 and 3 and 149 healthy children as a control group were included in this prospective, observational study. Patients receiving drugs that interact with warfarin, having chronic liver or renal disease, obesity, or thyroid dysfunctions were excluded. Polymerase chain reaction (real time and restriction fragment length polymorphism) was used to analyze the CYP2C9*2, CYP2C9*3, and VKORC1 polymorphisms. The ideal warfarin dose was calculated according to the patient's age, height, and the presence of CYP2C9*2, CYP2C9*3, and VKORC1 genetic polymorphisms. The mean daily administered doses and ideal doses were compared. Analysis of variance, Student's t-test, logistic regression analysis, and Pearson's correlation analysis were used for statistical analyses. RESULTS: The frequency of the CYP2C9 and VKORC1 genetic polymorphisms was determined as CYP2C9*1/*1 (54.6%), *1/*2 (16.4%), *1/*3 (24.2%), *2/*3 (2.9%), *3/*3 (1.9%), wild-type VKORC1 (26.6%), heterozygote alleles (52.7%), and mutant alleles (20.8%). Patients with allelic variants were found to require lower warfarin doses, and a 64.5% correlation was found between the calculated ideal doses and the administered warfarin doses. CONCLUSION: Considering CYP2C9 and VKORC1 genetic polymorphisms prior to commencing warfarin treatment will make it easier to reach target INRs and reduce the rate of complications. PMID- 27182618 TI - Use of strain and strain rate echocardiographic imaging to predict the progression of mitral stenosis: a 5-year follow-up study the progression of mitral stenosis: a 5-year follow-up study. AB - OBJECTIVE: Little information is available about echocardiographic progression of mitral stenosis (MS). The aim of this study was to investigate whether the left ventricular (LV) strain is a favorable method predicting the progression of MS. METHODS: Forty-eight patients with isolated mild-to-moderate MS were enrolled in this prospective cohort study. LV global longitudinal strain (GLS) and strain rate (GLSR) were measured by two-dimensional echocardiography (2-DE) at the baseline. Mitral valve area (MVA) was evaluated during the 5-year follow-up. The change in MVA from the beginning to the end of the surveillance period was determined as an indicator of progression. Pearson's correlation test was used, and significant differences between the groups were analyzed using the Student's t-test or the Mann-Whitney U test. At the end of follow-up, we evaluated the correlation between the change in MVA and both GLS-GLSR. GLS and GLSR are predictive factors for MS progression, whether or not it has been tested according to the receiver operating characteristics curve analysis. RESULTS: A meaningful correlation was detected between the change in MVA with both GLS and GLSR (r=0.924 and r=0.980, respectively, p<0.001). The cut-off value for GLS was identified as -16.98 (sensitivity 81%, specificity 96%, p<0.001) and for GLSR as 1.45 (sensitivity 95%, specificity 100%, p<0.001). Patients with MS having a value under (mathematically above) these cut-off values showed more rapid progression. CONCLUSION: The progression of MS can be predicted by GLS and GLSR measurements, which are evaluated via strain echocardiography. PMID- 27182619 TI - A Bayesian analysis on the (dis)utility of iterative-showup procedures: The moderating impact of prior probabilities. AB - A showup is an identification procedure in which a lone suspect is presented to the eyewitness for an identification attempt. Showups are commonly used when law enforcement personnel locate a suspect near the scene of a crime in both time and space but lack probable cause to make an arrest. If an eyewitness rejects a suspect from a showup, law enforcement personnel might find another suspect and run another showup. Indeed, law enforcement personnel might go through several iterations of finding suspects and running showups with the same eyewitness. We label this phenomenon the iterative-showup procedure. The consequence of this procedure is that innocent suspect identifications increase disproportionately to culprit identifications. This happens because there is only one culprit, but a seemingly endless supply of innocent suspects. We apply Bayesian modeling to single- and iterative-showup procedures to demonstrate that iterative showups are almost always associated with lower probative value. We demonstrate that the prior probabilities that later suspects are the culprit are greatly constrained by the posterior probabilities that earlier suspects were the culprit. Identifications from iterative-showup procedures are of questionable reliability. We review alternative investigative strategies that police might consider in order to limit the use of iterative-showup procedures. (PsycINFO Database Record PMID- 27182617 TI - Comparison of left atrial volume and function in non-dipper versus dipper hypertensives: A real-time three-dimensional echocardiography study. AB - OBJECTIVE: Non-dipper hypertension is associated with an increased cardiovascular morbidity and mortality. Besides this, the left atrial (LA) size and functions are accepted to be prognostic factors in various cardiovascular diseases. In this study, we aimed to evaluate the effect of nondipper hypertension on LA volume and functions using real-time three-dimensional echocardiography (RT3-DE). METHODS: Forty dipper and 52 non-dipper hypertensives enrolled in this prospective cross sectional study. Patients with any comorbidities that have a potential for causing structural cardiac alterations were excluded. Two-dimensional echocardiography (2-DE) and RT3-DE were performed to assess LA volumes and functions. The statistical tests used in this study were Shapiro-Wilk's test, Student's t-test, Mann-Whitney U test, chi-square test, Spearman's test, and Pearson's correlation test. RESULTS: LA minimal volume, LA volume before LA contraction, and LA total systolic volume were higher in non-dipper hypertensives than in dipper hypertensives (p<0.001, p=0.003, and p=0.03, respectively). Only, the 2-DE measurements of interventricular septal thickness and E/Em ratio were higher in non-dipper hypertensives (p=0.001 and p=0.03, respectively). There was a moderate correlation between LA minimal volume and LA volume before LA contraction with E/Em (r=0.31, p=0.007 and r=0.32, p=0.005, respectively). CONCLUSION: Although LA volume and passive LA systolic functions measured by RT3 DE are significantly increased in non-dipper hypertensives, the alterations in active LA systolic functions are not prominent. RT-3DE may be used to define LA volume and function alterations in conditions that have capabilities of adverse cardiac remodeling such as systemic hypertension. PMID- 27182620 TI - Does learning about race prevent substance abuse? Racial discrimination, racial socialization and substance use among African Americans. PMID- 27182621 TI - The Genomic Context and Corecruitment of SP1 Affect ERRalpha Coactivation by PGC 1alpha in Muscle Cells. AB - The peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC 1alpha) coordinates the transcriptional network response to promote an improved endurance capacity in skeletal muscle, eg, by coactivating the estrogen-related receptor-alpha (ERRalpha) in the regulation of oxidative substrate metabolism. Despite a close functional relationship, the interaction between these 2 proteins has not been studied on a genomic level. We now mapped the genome-wide binding of ERRalpha to DNA in a skeletal muscle cell line with elevated PGC-1alpha and linked the DNA recruitment to global PGC-1alpha target gene regulation. We found that, surprisingly, ERRalpha coactivation by PGC-1alpha is only observed in the minority of all PGC-1alpha recruitment sites. Nevertheless, a majority of PGC 1alpha target gene expression is dependent on ERRalpha. Intriguingly, the interaction between these 2 proteins is controlled by the genomic context of response elements, in particular the relative GC and CpG content, monomeric and dimeric repeat-binding site configuration for ERRalpha, and adjacent recruitment of the transcription factor specificity protein 1. These findings thus not only reveal a novel insight into the regulatory network underlying muscle cell plasticity but also strongly link the genomic context of DNA-response elements to control transcription factor-coregulator interactions. PMID- 27182623 TI - Palladium-Catalyzed Oxidative N-Dealkylation/Carbonylation of Tertiary Amines with Alkynes to alpha,beta-Alkynylamides. AB - The first highly effective Pd/C-catalyzed oxidative N-dealkylation/carbonylation of various aliphatic as well as cyclic tertiary amines with alkynes has been described. The selective sp(3) C-N bond activation of tertiary amines at the less steric side using O2 as a sole oxidant and a plausible reaction pathway for the reaction are discussed. The general and operationally simple methodology provides an alternative for the synthesis of a wide range of alk-2-ynamide derivatives under mild conditions. The present protocol is ecofriendly and practical, and it shows significant recyclability. PMID- 27182622 TI - KRAS and TP53 mutations in bronchoscopy samples from former lung cancer patients. AB - Mutations in the KRAS and TP53 genes have been found frequently in lung tumors and specimens from individuals at high risk for lung cancer and have been suggested as predictive markers for lung cancer. In order to assess the prognostic value of these two genes' mutations in lung cancer recurrence, we analyzed mutations in codon 12 of the KRAS gene and in hotspot codons of the TP53 gene in 176 bronchial biopsies obtained from 77 former lung cancer patients. Forty-seven patients (61.0%) showed mutations, including 35/77 (45.5%) in the KRAS gene and 25/77 (32.5%) in the TP53 gene, among them 13/77 (16.9%) had mutations in both genes. When grouped according to past or current smoking status, a higher proportion of current smokers showed mutations, in particular those in the TP53 gene (P = 0.07), compared with ex-smokers. These mutations were found in both abnormal lesions (8/20 or 40%) and histologically normal tissues (70/156 or 44.9%) (P = 0.812). They consisted primarily of G to A transition and G to T transversion in both the KRAS (41/56 or 73.2%) and TP53 (24/34 or 70.6%) genes, consistent with mutations found in lung tumors of smoking lung cancer patients. Overall, recurrence-free survival (RFS) among all subjects could be explained by age at diagnosis, tumor stage, tumor subtype, and smoking (P < 0.05, Cox proportional hazard). Therefore, KRAS and TP53 mutations were frequently detected in bronchial tissues of former lung cancer patients. However, the presence of mutation of bronchial biopsies was not significantly associated with a shorter RFS time. (c) 2016 Wiley Periodicals, Inc. PMID- 27182624 TI - Erratum: A meta-analysis on age-associated changes in blood DNA methylation: results from an original analysis pipeline for Infinium 450k data. PMID- 27182625 TI - Time to Diagnostic Evaluation After Mammographic Screening in an Urban Setting. AB - BACKGROUND: The Capital Breast Care Center (CBCC), a screening facility established to serve minority women, developed a culturally sensitive patient care paradigm that would address concerns of adherence to follow-up of abnormal results after initial mammogram. Women with abnormal mammograms are assigned a Black or Latina navigator who facilitates the additional workup needed by scheduling follow-up, arranging transportation, providing counsel/emotional support, and even accompanying them to diagnostic imaging or biopsy appointment. We present data on follow-up rates after breast cancer screening. METHODS: All patients seen at CBCC are entered into a prospectively collected database. We calculated intervals (in days) between the screening and diagnostic visits. Descriptive statistics and median time to follow-up are reported. Differences between Black and Hispanic women on time interval were tested by t-test. RESULTS: From January 2010 to December 2012, 4605 digital screening mammograms were performed. Fifty-two percent of the women self-identified as Black, 41% as Hispanic, 4% White, 2% Asian, and 1% as "other." Of the screening studies, 451 (9.8%) required additional workup, out of which 362 (80%) of the women returned for the recommended diagnostic imaging. The median interval between screening and diagnostic imaging was 39 days (range: 6-400). Of the 162 women recommended to have a core needle biopsy, 81.5% underwent biopsy within a median of 21 days (range: 0-221 days). CONCLUSION: At the CBCC, time to patient follow-up after initial mammographic screening is within the CDC-recommended performance standard of less than 60 days. For a population that historically has low rates of clinical follow-up, we attribute this reduction in delays to breast cancer diagnostic resolution to a culturally sensitive patient navigation program. Additional studies are needed to assess how the existing navigation program can be individualized/tailored to target the remaining 20% of women who did not adhere to the recommended workup. PMID- 27182626 TI - Clostridium Difficile Infection in Children: A Review. AB - Clostridium difficile is a sporogenic, anaerobic, Gram-positive, emerging enteric pathogen. It represents the most common cause of health care-associated diarrhoea in the United States, with significantly associated morbidity, mortality, and health care costs. Historically regarded as a little more than an innocent coloniser bystander of the gastrointestinal tract of children, C difficile has increasingly demonstrated its behaviour as a true pathogen in the paediatric age groups. This organism may be responsible for a broad spectrum of diseases in children, ranging from self-limiting secretory diarrhoea to life-threatening conditions, such as pseudomembranous colitis, toxic megacolon, intestinal perforation, and septic shock. The incidence and severity of C difficile infection are, however, not completely understood in this population. In particular, although asymptomatic carriage remains high among infants, the clinical significance of detecting C difficile in children aged 1 to 3 years is not fully understood. Moreover, recent epidemiological surveillance has demonstrated a rise in the incidence of C difficile infection, particularly in the community and in low-risk settings. Interestingly, such cases may not show the disease pattern to be associated with typical risk factors, such as recent exposure to antimicrobial drugs or on-going contacts with the health care system.The purpose of the present review is to present the features of C difficile infection that are unique to paediatric patients and to update paediatricians on information and recommendations regarding C difficile infection in children. PMID- 27182627 TI - Empirical Studies About Attendance at Religious Services and Health. PMID- 27182628 TI - Whole Teflon valves for handling droplets. AB - We propose and test a new whole-Teflon gate valve for handling droplets. The valve allows droplet plugs to pass through without disturbing them. This is possible due to the geometric design, the choice of material and lack of any pulses of flow generated by closing or opening the valve. The duct through the valve resembles a simple segment of tubing, without constrictions, change in lumen or side pockets. There are no extra sealing materials with different wettability or chemical resistance. The only material exposed to liquids is FEP Teflon, which is resistant to aggressive chemicals and fully biocompatible. The valve can be integrated into microfluidic systems: we demonstrate a complex system for culturing bacteria in hundreds of microliter droplet chemostats. The valve effectively isolates modules of the system to increase precision of operations on droplets. We verified that the valve allowed millions of droplet plugs to safely pass through, without any cross-contamination with bacteria between the droplets. The valve can be used in automating complex microfluidic systems for experiments in biochemistry, biology and organic chemistry. PMID- 27182630 TI - Chemical Dynamics Simulations of Intermolecular Energy Transfer: Azulene + N2 Collisions. AB - Chemical dynamics simulations were performed to investigate collisional energy transfer from highly vibrationally excited azulene (Az*) in a N2 bath. The intermolecular potential between Az and N2, used for the simulations, was determined from MP2/6-31+G* ab initio calculations. Az* is prepared with an 87.5 kcal/mol excitation energy by using quantum microcanonical sampling, including its 95.7 kcal/mol zero-point energy. The average energy of Az* versus time, obtained from the simulations, shows different rates of Az* deactivation depending on the N2 bath density. Using the N2 bath density and Lennard-Jones collision number, the average energy transfer per collision ?DeltaEc? was obtained for Az* as it is collisionally relaxed. By comparing ?DeltaEc? versus the bath density, the single collision limiting density was found for energy transfer. The resulting ?DeltaEc?, for an 87.5 kcal/mol excitation energy, is 0.30 +/- 0.01 and 0.32 +/- 0.01 kcal/mol for harmonic and anharmonic Az potentials, respectively. For comparison, the experimental value is 0.57 +/- 0.11 kcal/mol. During Az* relaxation there is no appreciable energy transfer to Az translation and rotation, and the energy transfer is to the N2 bath. PMID- 27182641 TI - Does Segregation Lead to Lower Birth Weight?: An Instrumental Variable Approach. AB - BACKGROUND: Racial residential segregation in the United States has been linked to racial differences in birth outcomes, with studies reporting associations between segregation and birth weight. However, this relationship is likely confounded, and many individual and neighborhood-level covariates included in previous models are likely mediators, potentially obscuring any causal impact of segregation on birth weight. METHODS: We compiled a record of non-Hispanic black and white singleton births to US-born/resident mothers in 2000, linked to segregation indices at the metropolitan statistical area (MSA) level in the non Southern US. Segregation was measured via the dissimilarity index. The outcomes were individual-level birth weight and the metropolitan statistical area-level black/white gap in birth weight. We instrumented for segregation using the railroad division index. We compared race-stratified ordinary least squares models to two-stage least squares models, with cluster robust standard errors. RESULTS: We estimated a 1.2 g decrease in black birth weight for every one percentage point increase in segregation (95% confidence interval [CI]: -1.9, 0.50) via ordinary least squares but a 2.8 g decrease (95% CI: -6.0, 0.48) using two-stage least squares. For white infants, our ordinary least squares estimate was 0.53 (95% CI: -0.23, 1.3), and our two-stage least squares estimate was in the opposite direction (-0.68, 95% CI: -3.5, 2.1). CONCLUSIONS: Ordinary least squares estimates may understate the effect of segregation on birth weight in blacks. Evidence from instrumental variable models was consistent with a causal impact of segregation on black birth outcomes, but estimates were imprecise and may be affected by weak instrument bias. PMID- 27182642 TI - Brief Report: Negative Controls to Detect Selection Bias and Measurement Bias in Epidemiologic Studies. AB - Biomedical laboratory experiments routinely use negative controls to identify possible sources of bias, but epidemiologic studies have infrequently used this type of control in their design or measurement approach. Recently, epidemiologists proposed the routine use of negative controls in observational studies and defined the structure of negative controls to detect bias due to unmeasured confounding. We extend this previous study and define the structure of negative controls to detect selection bias and measurement bias in both observational studies and randomized trials. We illustrate the strengths and limitations of negative controls in this context using examples from the epidemiologic literature. Given their demonstrated utility and broad generalizability, the routine use of prespecified negative controls will strengthen the evidence from epidemiologic studies. PMID- 27182629 TI - BDDCS, the Rule of 5 and drugability. AB - The Rule of 5 methodology appears to be as useful today in defining drugability as when it was proposed, but recognizing that the database that we used includes only drugs that successfully reached the market. We do not view additional criteria necessary nor did we find significant deficiencies in the four Rule of 5 criteria originally proposed by Lipinski and coworkers. BDDCS builds upon the Rule of 5 and can quite successfully predict drug disposition characteristics for drugs both meeting and not meeting Rule of 5 criteria. More recent expansions of classification systems have been proposed and do provide useful qualitative and quantitative predictions for clearance relationships. However, the broad range of applicability of BDDCS beyond just clearance predictions gives a great deal of further usefulness for the combined Rule of 5/BDDCS system. PMID- 27182643 TI - alpha3 Integrin of Cell-Cell Contact Mediates Kidney Fibrosis by Integrin-Linked Kinase in Proximal Tubular E-Cadherin Deficient Mice. AB - Loss of E-cadherin marks a defect in epithelial integrity and polarity during tissue injury and fibrosis. Whether loss of E-cadherin plays a causal role in fibrosis is uncertain. alpha3beta1 Integrin has been identified to complex with E cadherin in cell-cell adhesion, but little is known about the details of their cross talk. Herein, E-cadherin gene (Cdh1) was selectively deleted from proximal tubules of murine kidney by Sglt2Cre. Ablation of E-cadherin up-regulated alpha3beta1 integrin at cell-cell adhesion. E-cadherin-deficient proximal tubular epithelial cell displayed enhanced transforming growth factor-beta1-induced alpha smooth muscle actin (alpha-SMA) and vimentin expression, which was suppressed by siRNA silencing of alpha3 integrin, but not beta1 integrin. Up-regulation of transforming growth factor-beta1-induced alpha-SMA was mediated by an alpha3 integrin-dependent increase in integrin-linked kinase (ILK). Src phosphorylation of beta-catenin and consequent p-beta-catenin-Y654/p-Smad2 transcriptional complex underlies the transcriptional up-regulation of ILK. Kidney fibrosis after unilateral ureteric obstruction or ischemia reperfusion was increased in proximal tubule E-cadherin-deficient mice in comparison to that of E-cadherin intact control mice. The exacerbation of fibrosis was explained by the alpha3 integrin dependent increase of ILK, beta-catenin nuclear translocation, and alpha SMA/proximal tubular-specific Cre double positive staining in proximal tubular epithelial cell. These studies delineate a nonconventional integrin/ILK signaling by alpha3 integrin-dependent Src/p-beta-catenin-Y654/p-Smad2-mediated up regulation of ILK through which loss of E-cadherin leads to kidney fibrosis. PMID- 27182645 TI - DNA Methylation Leads to DNA Repair Gene Down-Regulation and Trinucleotide Repeat Expansion in Patient-Derived Huntington Disease Cells. AB - Huntington disease (HD) is an autosomal dominantly inherited disease that exhibits genetic anticipation of affected progeny due to expansions of a trinucleotide repeat (TNR) region within the HTT gene. DNA repair machinery is a known effector of TNR instability; however, the specific defects in HD cells that lead to TNR expansion are unknown. We hypothesized that HD cells would be deficient in DNA repair gene expression. To test this hypothesis, we analyzed expression of select DNA repair genes involved in mismatch/loop-out repair (APEX1, BRCA1, RPA1, and RPA3) in patient-derived HD cells and found each was consistently down-regulated relative to wild-type samples taken from unaffected individuals in the same family. Rescue of DNA repair gene expression by 5 azacytidine treatment identified DNA methylation as a mediator of DNA repair gene expression deficiency. Bisulfite sequencing confirmed hypermethylation of the APEX1 promoter region in HD cells relative to control, as well as 5-azacytidine induced hypomethylation. 5-Azacytidine treatments also resulted in stabilization of TNR expansion within the mutant HTT allele during long-term culture of HD cells. Our findings indicate that DNA methylation leads to DNA repair down regulation and TNR instability in mitotically active HD cells and offer a proof of principle that epigenetic interventions can curb TNR expansions. PMID- 27182646 TI - Conjugation of Docetaxel with Multiwalled Carbon Nanotubes and Codelivery with Piperine: Implications on Pharmacokinetic Profile and Anticancer Activity. AB - Nanotechnology-based drug products are emerging as promising agents to enhance the safety and efficacy of established chemotherapeutic molecules. Carbon nanotubes (CNTs), especially multiwalled CNTs (MWCNTs), have been explored for this potential owing to their safety and other desired attributes. Docetaxel (DTX) is an indispensable anticancer agent, which has wide applicability in variety of cancers. However, the potential of DTX is still not completely harvested due to problems like poor aqueous solubility, low tissue permeability, poor bioavailability, high first pass metabolism, and dose-related toxicity. Hence, it was proposed to attach DTX to MWCNTs and coadminister it along with piperine with an aim to enhance the tissue permeation, anticancer activity, and bioavailability. The Fourier transform infrared, UV, and NMR spectroscopic data confirmed successful conjugation of DTX to MWCNTs and adsorption of piperine onto MWCNTs. The codelivery MWCNT-based system offered drug release moderation and better cancer cell toxicity than that of plain DTX as well as DTX-CNT conjugate. The pharmacokinetic profile of DTX was exceptionally improved by the conjugation, in general, and coadministration with piperine, in specific vis-a-vis plain drug. Hence, the dual approach of MWCNTs conjugation and piperine coadministration can serve as a beneficial option for enhancement of the performance of DTX in cancer chemotherapy. PMID- 27182647 TI - Domperidone is Commonly Prescribed With QT-Interacting Drugs: Review of a Community-based Practice and a Postmarketing Adverse Drug Event Reporting Database. AB - INTRODUCTION: Domperidone, a peripheral D2 dopamine receptor antagonist, has efficacy for treatment of nausea, dyspepsia, and gastroparesis. Domperidone prolongs the QT interval (QTc), and may cause life-threatening arrhythmias. METHODS: Electronic medical records for all patients receiving domperidone in the NorthShore University HealthSystem from January 1, 2008 to December 1, 2013 were reviewed. All concomitant medications were noted. The coadministration of QT interacting medications was determined. Electrocardiogram (EKG) evaluation before and during domperidone therapy was noted. A query of the FDA Adverse Event Reporting System (FAERS) database was also performed. Individual reports from the FAERS Web site from January 2008 to June 2014 were downloaded and analyzed. The database was queried for all reports of adverse events with domperidone. Coadministration of QT-interacting medications was noted. Cardiac events that potentially were related to prolongation of the QTc were examined. RESULTS: In total, 108 of 155 patients (69.7%) were coprescribed QT-interacting drugs along with domperidone. Fifty-nine of 155 patients (38.1%) underwent a baseline EKG and 9 (15.3%) had prolongation of the QTc at initiation. Forty patients (25.8%) had a follow-up EKG and 13 (32.5%) had prolongation of the QTc. All 13 were coprescribed QT-interacting medications. On the FAERS, 221 nonfatal cardiac events were reported in domperidone patients; of these, 162 (73.3%) occurred in patients receiving QT-interacting medications. Coprescription occurred in 53 of 151 deaths (35.1%) and in 16 of 61 cardiac arrests (26.2%). CONCLUSIONS: Coprescribing of QT-prolonging medications and inconsistent EKG monitoring occur in patients receiving domperidone, placing these patients at risk for arrhythmias. PMID- 27182644 TI - Cytoplasmic Cyclin E and Phospho-Cyclin-Dependent Kinase 2 Are Biomarkers of Aggressive Breast Cancer. AB - Cyclin E and its co-activator, phospho-cyclin-dependent kinase 2 (p-CDK2), regulate G1 to S phase transition and their deregulation induces oncogenesis. Immunohistochemical assessments of these proteins in cancer have been reported but were based only on their nuclear expression. However, the oncogenic forms of cyclin E (low molecular weight cyclin E or LMW-E) in complex with CDK2 are preferentially mislocalized to the cytoplasm. Here, we used separate nuclear and cytoplasmic scoring systems for both cyclin E and p-CDK2 expression to demonstrate altered cellular accumulation of these proteins using immunohistochemical analysis. We examined the specificity of different cyclin E antibodies and evaluated their concordance between immunohistochemical and Western blot analyses in a panel of 14 breast cell lines. Nuclear versus cytoplasmic staining of cyclin E readily differentiated full-length from LMW-E, respectively. We also evaluated the expression of cyclin E and p-CDK2 in 1676 breast carcinoma patients by immunohistochemistry. Cytoplasmic cyclin E correlated strongly with cytoplasmic p-CDK2 (P < 0.0001), high tumor grade, negative estrogen/progesterone receptor status, and human epidermal growth factor receptor 2 positivity (all P < 0.0001). In multivariable analysis, cytoplasmic cyclin E plus phosphorylated CDK2 (as one variable) predicted breast cancer recurrence-free and overall survival. These results suggest that cytoplasmic cyclin E and p-CDK2 can be readily detected with immunohistochemistry and used as clinical biomarkers for aggressive breast cancer. PMID- 27182648 TI - Histologic Disease in Chinese Chronic Hepatitis B Patients With Low Viral Loads and Persistently Normal Alanine Aminotransferase Levels. AB - BACKGROUND/AIM: We aimed to evaluate the histopathologic characteristics of HBeAg negative chronic hepatitis B patients with low hepatitis B virus (HBV) DNA levels (<2000 IU/mL) and persistently normal ALT levels and to determine indicators of significant liver disease. METHODS: We examined 102 consecutive subjects who underwent percutaneous liver biopsy. Significant predictors of liver disease (stage >=2 fibrosis or stage 1 fibrosis plus grade >=2 inflammation), including demographic, clinical, and laboratory variables, were evaluated by means of univariate and multivariate logistic regression analyses. RESULTS: Among the patients, 75.5% (77/102) had grade 0-1 inflammation and 77.5% (79/102) had stage 0-1 fibrosis. However, 38.2% (39/102) had significant liver disease. There were no statistically significant differences in clinical parameters such as age, biochemical profile, HBV DNA levels, HBsAg levels, and platelet count between patients with significant and those with nonsignificant liver disease. Patients with significant liver disease had higher values of aspartate transferase-to platelet ratio index (APRI) and FIB-4 index compared with those with nonsignificant liver disease (0.35+/-0.21 vs. 0.27+/-0.12, P=0.02; 1.58+/-0.97 vs. 1.13+/-0.54, P=0.009, respectively). The area under the receiver operating characteristic (AUROC) curve of APRI for identifying active liver histology was 0.64 (95% CI, 0.53-0.75; P=0.019); the cutoff value was 0.24 with a sensitivity of 74% and specificity of 55%. In comparison, FIB-4 had equal power (the AUROC was 0.66) in predicting active liver histology. CONCLUSION: Among patients presenting with low HBV DNA levels and normal ALT levels, about 38.2% had significant liver disease. Neither serum HBsAg nor HBV DNA levels correlate with liver histology. However, APRI>=0.24 might be considered an indicator of liver biopsy. PMID- 27182649 TI - Polystyrene latex particles containing europium complexes prepared by miniemulsion polymerization using bovine serum albumin as a surfactant for biochemical diagnosis. AB - Luminescent particles have been attracting significant attention because they can be used in biochemical applications, such as detecting and imaging biomolecules. In this study, luminescent polystyrene latex particles were prepared through miniemulsion polymerization of styrene with dissolved europium complexes in the presence of bovine serum albumin (BSA) and poly(ethylene glycol) monomethoxy methacrylate as surfactants. The solubility of the europium complex in styrene has a strong effect on the yield of the particle. Europium tris(2-thenoyl trifluoroacetonate) di(tri-n-octyl phosphine oxide), which has a high solubility in styrene, was sufficiently incorporated into the polystyrene particles compared to europium tris(2-thenoyl trifluoroacetonate), which has a low solubility in styrene. The luminescence property of the europium complex could remain intact even after its incorporation through the miniemulsion polymerization. In the aqueous dispersion, the resulting particles could emit strong luminescence, which is a characteristic of the europium complex. The antibody fragments were covalently attached to BSA-covered particles after a reaction with a bifunctional linker, N-(6-maleimidocaproyloxy)succinimide. The time-resolved fluoroimmunoassay technique showed that 3.3pg/mL of human alpha-fetoproteins (AFP) can be detected by using the resulting luminescent particles. An immunochromatographic assay using the resulting particles was also performed as a convenient method to qualitatively detect biomolecules. The detection limit of AFP measured by the immunochromatographic assay was determined to be 2000pg/mL. These results revealed that the luminescent particles obtained in this study can be utilized for the highly sensitive detection of biomolecules and in vitro biochemical diagnosis. PMID- 27182650 TI - A label-free electrochemical aptasensor based on graphene oxide/double-stranded DNA nanocomposite. AB - A novel label-free electrochemical impedance aptasensor based on a gold nanoparticles/double-stranded DNA-graphene (AuNPs/dsDNA-GO) nanocomposite modified glassy carbon electrode was presented for quantitative determination of thrombin. GO was covalently functionalized with dsDNA via a facile amidation process, and then AuNPs were electrodeposited onto the surface of dsDNA-GO. The morphology, conductivity and interaction of the as-prepared nanocomposites were characterized by scanning electron microscopy, cyclic voltammetry, electrochemical impedance spectroscopy (EIS), Raman and Fourier transform infrared spectroscopy. The thrombin-binding aptamer (TBA) was conjugated to AuNPs via gold-thiol chemistry to construct electrochemical aptasensing platform, and the specific recognition between TBA and thrombin was monitored by EIS. Under optimum conditions, thrombin could be quantified in a wide range of 0.1-100nM (R(2)=0.9960) with low detection limit of 0.06nM (S/N=3). PMID- 27182651 TI - Pulmonary surfactant mitigates silver nanoparticle toxicity in human alveolar type-I-like epithelial cells. AB - Accompanying increased commercial applications and production of silver nanomaterials is an increased probability of human exposure, with inhalation a key route. Nanomaterials that deposit in the pulmonary alveolar region following inhalation will interact firstly with pulmonary surfactant before they interact with the alveolar epithelium. It is therefore critical to understand the effects of human pulmonary surfactant when evaluating the inhalation toxicity of silver nanoparticles. In this study, we evaluated the toxicity of AgNPs on human alveolar type-I-like epithelial (TT1) cells in the absence and presence of Curosurf((r)) (a natural pulmonary surfactant substitute), hypothesising that the pulmonary surfactant would act to modify toxicity. We demonstrated that 20nm citrate-capped AgNPs induce toxicity in human alveolar type I-like epithelial cells and, in agreement with our hypothesis, that pulmonary surfactant acts to mitigate this toxicity, possibly through reducing AgNP dissolution into cytotoxic Ag(+) ions. For example, IL-6 and IL-8 release by TT1 cells significantly increased 10.7- and 35-fold, respectively (P<0.01), 24h after treatment with 25MUg/ml AgNPs. In contrast, following pre-incubation of AgNPs with Curosurf((r)), this effect was almost completely abolished. We further determined that the mechanism of this toxicity is likely associated with Ag(+) ion release and lysosomal disruption, but not with increased reactive oxygen species generation. This study provides a critical understanding of the toxicity of AgNPs in target human alveolar type-I-like epithelial cells and the role of pulmonary surfactant in mitigating this toxicity. The observations reported have important implications for the manufacture and application of AgNPs, in particular for applications involving use of aerosolised AgNPs. PMID- 27182652 TI - Effect of proteins on the surface microstructure evolution of a CoCrMo alloy in bio-tribocorrosion processes. AB - Under tribological contact, the subsurface microstructure of CoCrMo alloys for artificial joint implants can be changed and affect the life and safety of such devices. As one of the most important and abundant components in the synovial fluid, proteins play a key role in affecting the bio-tribocorrosion behaviors of metal implants. The effect of proteins on the subsurface microstructure evolution of a CoCrMo alloy was investigated using a transmission electron microscope (TEM) in this study. The result shows that proteins have two main effects on the subsurface's evolution: forming a multilayered structure and causing severer subsurface deformation. The tribo-film can protect the passive film from scrapping, and then the passive film can reduce or even suppress the stacking fault annihilation by blocking the access to the metal surface. It leads to the stacking fault being diffused towards the deeper area and a strain accumulation in the subsurface, before inducing a severer deformation. On the other hand, the effect of proteins results in the location changing from the top surface to be underneath the top surface, where the maximum frictional shear stress occurs. This can cause a deeper deformation. PMID- 27182653 TI - Thermoresponsive poly[tri(ethylene glycol) monoethyl ether methacrylate]-peptide surfaces obtained by radiation grafting-synthesis and characterisation. AB - This report demonstrates the feasibility of radiation grafting for the preparation of polymer layers functionalised with short peptide ligands which promote cell adhesion. Thermoresponsive poly [tri(ethylene glycol) monoethyl ether methacrylate] (PTEGMA) layers were synthesised on a polypropylene substrate by post-irradiation grafting. A cell adhesion moiety, the CF-IKVAVK peptide modified with a methacrylamide function and a fluorescent label were introduced to the surface during the polymerisation process. The amount of CF-IKVAVK was easily controlled by changing its concentration in the reaction mixture. The changes in the surface composition, morphology, philicity and thickness at each step of the polypropylene functionalisation confirmed that the surface modification procedures were successful. The increase in environmental temperature above the cloud point temperature of PTEGMA caused a decrease in surface philicity. The obtained PTEGMA and PTEGMA-peptide surfaces above TCP were tested as scaffolds for fibroblast sheet culture and temperature induced detachment. PMID- 27182654 TI - Unfolding and inactivation of proteins by counterions in protein-nanoparticles interaction. AB - In this work, the structure and activity of proteins; such as, hen egg lysozyme (HEWL) and calf intestine alkaline phosphatase (CIAP); have been investigated after incubation with surface coated iron oxide nanoparticles (IONPs) in water. IONPs were coated with counterions bound charge-ligands and were named as the charge-ligand counterions iron oxide nanoparticles (CLC-IONPs). The coating was done with tri-lithium citrate (TLC) and tri-potassium citrate (TKC) to have negative surface charge of CLC-IONPs and Li(+) and K(+), respectively, as counterions. To have positive surface charge, IONPs were coated with cetylpyridinium chloride (CPC) and cetylpyridinium iodide (CPI) having Cl(-) and I(-), respectively, as counterions. The secondary structure of proteins was measured using far ultraviolet circular dichroism (CD) spectroscopy which showed that both proteins were irreversibly unfolded after incubation with CLC-IONPs. The unfolded proteins were seen to be functionally inactive, as confirmed through their activity assays, i.e., HEWL with Escherichia coli (E. coli) and CIAP with para-nitrophenyl phosphate (pNPP). Additionally, we have observed that monomeric hemoglobin (Hb) from radio-resistant insect Chironomus ramosus (ChHb) was also partially unfolded upon interaction with CLC-IONPs. This work clearly shows the role of counterions in protein inactivation via protein-nanoparticles interaction and, therefore, CLC-IONPs could be used for therapeutic purpose. PMID- 27182655 TI - Experimental evidence for the mode of action based on electrostatic and hydrophobic forces to explain interaction between chitosans and phospholipid Langmuir monolayers. AB - The interaction between chitosans and Langmuir monolayers mimicking cell membranes has been explained with an empirical scheme based on electrostatic and hydrophobic forces, but so far this has been tested only for dimyristoyl phosphatidic acid (DMPA). In this paper, we show that the mode of action in such a scheme is also valid for dipalmitoyl phosphatidyl choline (DPPC) and dipalmitoyl phosphatidyl glycerol (DPPG), whose monolayers were expanded and their compressibility modulus decreased by interacting with chitosans. In general, the effects were stronger for the negatively charged DPPG in comparison to DPPC, and for the low molecular weight chitosan (LMWChi) which was better able to penetrate into the hydrophobic chains than the high molecular weight chitosan (Chi). Penetration into the hydrophobic chains was confirmed with polarization modulated infrared reflection absorption spectroscopy (PM-IRRAS) and sum frequency generation (SFG) spectroscopy. A slight reduction in conformational order of the lipid chains induced by the chitosans was quantitatively estimated by measuring the ratio between the intensities of the methyl (r(+)) and methylene (d(+)) peaks in the SFG spectra for DPPG. The ratio decreased from 35.6 for the closely packed DPPG monolayer to 7.0 and 6.6 for monolayers containing Chi and LMWChi, respectively. Since in both cases there was a significant phospholipid monolayer expansion, the incorporation of chitosans led to chitosan-rich and lipid-rich condensed domains, which mantained conformational order for their hydrophobic tails. The stronger effects from LMWChi are ascribed to an easier access to the hydrophobic tails, as corroborated by measuring aggregation in solution with dynamic light scattering, where the hydrodynamic radius for LMWChi was close to half of that for Chi. Taken together, the results presented here confirm that the same mode of action applies to different phospholipids that are important constituents of mammalian (DPPC) and bacterial (DPPG) cell membranes. PMID- 27182656 TI - One-pot fabricating Fe3O4/graphene nanocomposite with excellent biocompatibility and non-toxicity as a negative MR contrast agent. AB - We report a facile approach to synthesize water-dispersible nanocomposite with Fe3O4 nanoparticles (NPs) attached to graphene (G), which combines the growth of Fe3O4NPs and the reduction of graphene oxide (GO) in one single step. The unique hydrophilic surface structure of Fe3O4/G nanocomposite leads to it being colloidally stable, non-cytotoxic, well-dispersible and biocompatible in aqueous solution verified via bio-experiments. In vivo tests also prove that Fe3O4/G nanocomposite, which can be cleared from the body through the metabolic processes, is harmless to the living body. Most importantly, the Fe3O4/G nanocomposite showed T2relaxivity (123.04mM(-1)s(-1)) indicating its potential as a sensitive T2 contrast agent. PMID- 27182658 TI - Thermodynamics of Anharmonic Systems: Uncoupled Mode Approximations for Molecules. AB - The partition functions, heat capacities, entropies, and enthalpies of selected molecules were calculated using uncoupled mode (UM) approximations, where the full-dimensional potential energy surface for internal motions was modeled as a sum of independent one-dimensional potentials for each mode. The computational cost of such approaches scales the same with molecular size as standard harmonic oscillator vibrational analysis using harmonic frequencies (HO(hf)). To compute thermodynamic properties, a computational protocol for obtaining the energy levels of each mode was established. The accuracy of the UM approximation depends strongly on how the one-dimensional potentials of each modes are defined. If the potentials are determined by the energy as a function of displacement along each normal mode (UM-N), the accuracies of the calculated thermodynamic properties are not significantly improved versus the HO(hf) model. Significant improvements can be achieved by constructing potentials for internal rotations and vibrations using the energy surfaces along the torsional coordinates and the remaining vibrational normal modes, respectively (UM-VT). For hydrogen peroxide and its isotopologs at 300 K, UM-VT captures more than 70% of the partition functions on average. By contrast, the HO(hf) model and UM-N can capture no more than 50%. For a selected test set of C2 to C8 linear and branched alkanes and species with different moieties, the enthalpies calculated using the HO(hf) model, UM-N, and UM-VT are all quite accurate comparing with reference values though the RMS errors of the HO model and UM-N are slightly higher than UM-VT. However, the accuracies in entropy calculations differ significantly between these three models. For the same test set, the RMS error of the standard entropies calculated by UM-VT is 2.18 cal mol(-1) K(-1) at 1000 K. By contrast, the RMS error obtained using the HO model and UM-N are 6.42 and 5.73 cal mol(-1) K(-1), respectively. For a test set composed of nine alkanes ranging from C5 to C8, the heat capacities calculated with the UM-VT model agree with the experimental values to within a RMS error of 0.78 cal mol(-1) K(-1), which is less than one-third of the RMS error of the HO(hf) (2.69 cal mol(-1) K(-1)) and UM-N (2.41 cal mol(-1) K( 1)) models. PMID- 27182657 TI - Functional mesoporous silica nanoparticles (MSNs) for highly controllable drug release and synergistic therapy. AB - Synergistic therapy involving two or more therapeutic agents with different anticancer mechanisms represents a promising approach to eradicate chemotherapy refractory cancers. However, the preparation of a synergistic therapy platform generally involves complicated procedures to encapsulate different therapeutic agents and thereby increases the purification difficulty. In this work, we reported a simple but robust strategy to prepare a highly controllable drug delivery system (DDS) for synergistic cancer therapy. To construct this robust DDS, mesoporous silica nanoparticles (MSNs) were employed as a nanoplatform to encapsulate anticancer drug doxorubicin (DOX). After using a tumor-targeting cellular membrane-penetrating peptide (TCPP) and a mitochondria-targeting therapeutic peptide (TPP) to seal the surface pores via disulfide bonds, these newly developed MSNs can target cancer cells, penetrate cell membrane and rapidly release anticancer drug and mitochondria-targeted peptide in cytoplasm, inducing a remarkable synergistic anticancer effect. The new design concept reported here will promote the development of targeted and smart DDSs for synergistic cancer therapy. PMID- 27182659 TI - Expansion of the Known Host Range of the Microsporidium, Pseudoloma neurophilia. AB - The microsporidium, Pseudoloma neurophilia, is the most common infectious organism found in laboratory zebrafish colonies. Many currently used zebrafish lines originally came from pet store fish, and the initial description of P. neurophilia came from zebrafish obtained from a retail pet store. However, as P. neurophilia has not been described from wild-caught zebrafish, whether P. neurophilia is a natural pathogen of zebrafish is an open question. The pooling of fish of different species in the aquarium fish trade is common and a generalist parasite could be transmitted to novel hosts in this scenario. We determined that P. neurophilia can infect seven species of fishes from five families by cohabitation with infected zebrafish: Betta splendens, Xiphophorus maculatus, Devario aequipinnatus, Pimephales promelas, Oryzias latipes, Carassius auratus and Paracheirodon innesi. Infections in these fishes were histologically similar to those of zebrafish. We include a case report of a laboratory population of fathead minnows with naturally acquired P. neurophilia infections. With such a broad host range, including several fish families, other laboratory fishes should be screened routinely for this and other microsporidian parasites. PMID- 27182660 TI - A two-stage method to correct aberrations induced by slide slant in bright-field microscopy. AB - To achieve optimal image quality in bright field microscopy, the slide surface should be perpendicular to the optical axis of the microscope. However, in the recently proposed "slanted scan" slide acquisition technique, scan speed is increased by purposely slanting the slide by a small angle (of 3-5 degrees ) so that multiple focal depths can be imaged simultaneously. In this case, the slanted slide introduces a bend in the point spread function (PSF), resulting in a coma and other aberrations that degrade image quality. In this paper, we propose a two-stage deconvolution method specifically designed to correct the aberrations induced by a slanted scan, but with general applicability to high resolution bright-field microscopy. Specifically, we initially apply phase deconvolution to correct the dominating coma aberration, before applying a conventional semi-blind deconvolution method to further improve image resolution and contrast. We also propose a novel method to estimate the degree of coma aberration and the PSF of the optics utilising actual cytology specimens. The efficacy of the proposed algorithm is demonstrated quantitatively on simulated data, against a ground-truth (object) image, and qualitatively on cervical cytology specimens. Results demonstrate both improved convergence speed of the two-stage approach, especially when correcting the bend in the PSF, and a resultant image quality that is comparable to a conventionally (flat) scanned specimen. PMID- 27182661 TI - Structural determination of the polysaccharide isolated from biofilms produced by a clinical strain of Klebsiella pneumoniae. AB - Klebsiella pneumoniae are Gram negative opportunistic pathogens producing capsular (K) polysaccharides. Seventy-seven different K antigens have been described and they are the basis for K serotyping. Capsular polysaccharides are important virulence factors and have a relevant role for the structure of biofilm communities. Nevertheless, little information is available on the polysaccharides produced in biofilm matrices by Klebsiella spp. In the present study, a clinical isolate of Klebsiella pneumoniae was grown both on cellulose membranes deposited on agar plates, where it formed an adherent biofilm, and in liquid medium, where it formed floating biofilms (flocs). Extraction and purification of the polysaccharide fraction showed that only one main carbohydrate polymer was present in both adherent biofilms and flocs. Composition and linkage analysis, Smith degradation followed by ESI-MS, 1D and 2D NMR spectroscopy revealed that the polysaccharide belong to the type K24 and has the following structure. PMID- 27182662 TI - Membrane anchoring stabilizes and favors secretion of New Delhi metallo-beta lactamase. AB - Carbapenems, 'last-resort' beta-lactam antibiotics, are inactivated by zinc dependent metallo-beta-lactamases (MBLs). The host innate immune response withholds nutrient metal ions from microbial pathogens by releasing metal chelating proteins such as calprotectin. We show that metal sequestration is detrimental for the accumulation of MBLs in the bacterial periplasm, because those enzymes are readily degraded in their nonmetallated form. However, the New Delhi metallo-beta-lactamase (NDM-1) can persist under conditions of metal depletion. NDM-1 is a lipidated protein that anchors to the outer membrane of Gram-negative bacteria. Membrane anchoring contributes to the unusual stability of NDM-1 and favors secretion of this enzyme in outer-membrane vesicles (OMVs). OMVs containing NDM-1 can protect nearby populations of bacteria from otherwise lethal antibiotic levels, and OMVs from clinical pathogens expressing NDM-1 can carry this MBL and the blaNDM gene. We show that protein export into OMVs can be targeted, providing possibilities of new antibacterial therapeutic strategies. PMID- 27182665 TI - Cysteine containing dipeptides show a metal specificity that matches the composition of seawater. AB - Model prebiotic dipeptide sequences were identified by bioinformatics and DFT and molecular dynamics calculations. The peptides were then synthesized and evaluated for metal affinity and specificity. Cysteine containing dipeptides were not associated with metal affinities that followed the Irving-Williams series but did follow the concentration trends found in seawater. PMID- 27182663 TI - The antitumor toxin CD437 is a direct inhibitor of DNA polymerase alpha. AB - CD437 is a retinoid-like small molecule that selectively induces apoptosis in cancer cells, but not in normal cells, through an unknown mechanism. We used a forward-genetic strategy to discover mutations in POLA1 that coincide with CD437 resistance (POLA1(R)). Introduction of one of these mutations into cancer cells by CRISPR-Cas9 genome editing conferred CD437 resistance, demonstrating causality. POLA1 encodes DNA polymerase alpha, the enzyme responsible for initiating DNA synthesis during the S phase of the cell cycle. CD437 inhibits DNA replication in cells and recombinant POLA1 activity in vitro. Both effects are abrogated by the identified POLA1 mutations, supporting POLA1 as the direct antitumor target of CD437. In addition, we detected an increase in the total fluorescence intensity and anisotropy of CD437 in the presence of increasing concentrations of POLA1 that is consistent with a direct binding interaction. The discovery of POLA1 as the direct anticancer target for CD437 has the potential to catalyze the development of CD437 into an anticancer therapeutic. PMID- 27182666 TI - Recent government regulations in the United States seek to ensure the effectiveness of antibiotics by limiting their agricultural use. AB - The development of bacteria resistant to antibiotics is viewed as a medical health threat. Because thousands of people die every year due to antibiotic resistant bacteria, efforts are underway to reduce antibiotic usage which in turn will reduce the development of antibiotic-resistant bacteria. In the United States, the use of antibiotics in the production of food animals to enhance animal growth has been identified as contributing to resistance. In 2015, a veterinary feed directive was adopted by the U.S. federal government prohibiting nontherapeutic uses of antibiotics in food animals that should reduce usage. The continued usage of antibiotics by producers for preventing disease may mean the directive is insufficient to reduce nontherapeutic antibiotic administration. This may lead some consumers to seek meat products from animals raised without antibiotics. A governmentally-sponsored labeling program could encourage reduction in antibiotic usage. PMID- 27182664 TI - A cascading activity-based probe sequentially targets E1-E2-E3 ubiquitin enzymes. AB - Post-translational modifications of proteins with ubiquitin (Ub) and ubiquitin like modifiers (Ubls), orchestrated by a cascade of specialized E1, E2 and E3 enzymes, control a wide range of cellular processes. To monitor catalysis along these complex reaction pathways, we developed a cascading activity-based probe, UbDha. Similarly to the native Ub, upon ATP-dependent activation by the E1, UbDha can travel downstream to the E2 (and subsequently E3) enzymes through sequential trans-thioesterifications. Unlike the native Ub, at each step along the cascade, UbDha has the option to react irreversibly with active site cysteine residues of target enzymes, thus enabling their detection. We show that our cascading probe 'hops' and 'traps' catalytically active Ub-modifying enzymes (but not their substrates) by a mechanism diversifiable to Ubls. Our founder methodology, amenable to structural studies, proteome-wide profiling and monitoring of enzymatic activity in living cells, presents novel and versatile tools to interrogate Ub and Ubl cascades. PMID- 27182667 TI - The role of companions in outpatient seizure clinic interactions: A pilot study. AB - PURPOSE: This study explored contributions that patients' companions (seizure witnesses) make to interactions in the seizure clinic and whether the nature of the companions' interactional contributions can help with the differentiation of epilepsy and psychogenic nonepileptic seizures (PNES). METHODS: Conversation analysis methods were used to examine video recordings and transcripts of neurologists' interactions with patients referred to a specialist seizure clinic and their companions. RESULTS: The companions' behavior correlated with interactional features previously observed to distinguish patients with epilepsy from patients with PNES. Patients with PNES, but not those with epilepsy, tended to exhibit interactional resistance to the doctor's efforts to find out more about their seizure experiences and, thereby, encouraged greater interactional contribution from companions. CONCLUSION: The contributions that companions make (in part, prompted by patient's interactional behavior) may provide additional diagnostic pointers in this clinical setting, and a number of candidate features that may help clinicians distinguish between epilepsy and PNES when the patient is accompanied by a seizure witness are described. However, companion contributions may limit the doctor's ability to identify linguistic and interactional features with previously demonstrated diagnostic potential in the conversational contributions made by patients themselves. To help offset potential diagnostic losses, doctors may need to explicitly discuss the role of the companion in the consultation when a seizure witness (or another companion) accompanies the patient. PMID- 27182668 TI - Online reconstruction of 3D magnetic particle imaging data. AB - Magnetic particle imaging is a quantitative functional imaging technique that allows imaging of the spatial distribution of super-paramagnetic iron oxide particles at high temporal resolution. The raw data acquisition can be performed at frame rates of more than 40 volumes s(-1). However, to date image reconstruction is performed in an offline step and thus no direct feedback is available during the experiment. Considering potential interventional applications such direct feedback would be mandatory. In this work, an online reconstruction framework is implemented that allows direct visualization of the particle distribution on the screen of the acquisition computer with a latency of about 2 s. The reconstruction process is adaptive and performs block-averaging in order to optimize the signal quality for a given amount of reconstruction time. PMID- 27182669 TI - The rolling evolution of biomedical science as an essential tool in modern clinical practice. AB - The British Journal of Biomedical Science is committed to publishing high-quality original research that represents a clear advance in the practice of biomedical science, and reviews that summarise recent advances in the field of biomedical science. The overall aim of the Journal is to provide a platform for the dissemination of new and innovative information on the diagnosis and management of disease that is valuable to the practicing laboratory scientist. The Editorial that follows describes the Journal and provides a perspective of its aims and objectives. PMID- 27182670 TI - British Journal of Biomedical Science in 2015: what have we learned? AB - In 2015, the British Journal of Biomedical Science published 47 reports on topics relating to the various disciplines within biomedical science. Of these, the majority were in infection science (15 in microbiology and two in virology) and blood science (seven in biochemistry, four in haematology, three in immunology and one in transplantation), with a smaller number in cellular sciences (four reports) and with one review across disciplines. The present report will summarise key aspects of these publications that are of greatest relevance to laboratory scientists. PMID- 27182671 TI - Platelet function testing: from routine to specialist testing. AB - Platelets have many functions within the haemostatic system, and when these actions are diminished for whatever reason, a bleeding tendency can manifest. Unravelling the reason(s) for this bleeding can be complex due to the multiple roles platelets perform. This review seeks to explain each level of platelet testing moving from those performed at local hospital laboratories to those performed by specialist centres and university research departments. It will examine the testing available and discuss when to move on to additional testing. PMID- 27182672 TI - Red blood cell distribution width and haemoglobin are associated with hospital admission in patients with acute allergic reactions. AB - INTRODUCTION: Red blood cell distribution width (RDW) is significantly associated with a variety of human disorders. This study aimed to investigate whether RDW value at admission may predict the need of hospitalisation in patients presenting to the emergency department (ED) with acute allergic reactions. MATERIALS AND METHODS: The study population consisted of adult patients (aged > 17) admitted to the ED for acute allergic reactions. RESULTS: One hundred and thirty-two subjects were included, 12 of whom (9%) required hospital admission for severity of symptoms. Patients who needed hospital admission displayed significantly lower values of haemoglobin and significantly higher values of RDW-coefficient of variation (RDW-CV). In multivariate analysis, haemoglobin and RDW-CV were found to be independent predictors of hospital admission. The area under the curve (AUC), sensitivity and specificity for predicting hospital admission were 0.72, 0.88 and 0.42 for haemoglobin and 0.73, 0.88 and 0.50 for RDW-CV, respectively. The combination of these tests (both positive) was characterised by 0.76 AUC, 0.83 sensitivity, 0.67 specificity, 0.96 negative predictive value and 0.30 positive predictive. DISCUSSION: The results of this study suggest that two common and inexpensive parameters such as haemoglobin and RDW are independent predictors of hospital admission in patients presenting to the ED with acute allergic reactions. PMID- 27182673 TI - Reduced penicillin susceptibility of group B Streptococcus: an assessment of emergence in Grampian, Scotland. PMID- 27182674 TI - Fine needle aspiration cytology for lymph nodes: a three-year study. AB - BACKGROUND AND AIMS: The cytologic patterns of lymph node fine needle aspirations (FNAs) exhibit a wide variation in different diseases and in different ethnic groups in various geographical locations. Knowledge of lymphadenopathy patterns in a given geographical region is essential for making a confident diagnosis of suspected disease in that location. In the present study, we assessed the cytologic patterns of lymph node aspirations in patients in the Huangdao region of China. METHODS: A three-year retrospective study design was conducted on FNA cytology samples from the lymph nodes of patients in our hospital between January 2011 and December 2014. RESULTS: A total of 2136 lymph nodes were aspirated during the study period. Cytologic analysis of the lymph nodes revealed the following: malignancy, 53.6%; chronic non-specific lymphadenitis, 15.2%; reactive lymph node, 7.5%; pyogenic abscess, 2.9%; tuberculosis lymphadenitis, 8.7%; Hodgkin lymphoma, 4.8%; and non-Hodgkin lymphoma, 7.16%. The 30-50 year age group was the most affected age group, while lymphadenopathy in the >60 year age group was less frequent. Cervical lymph nodes were the most frequent site for lymphadenopathy in women (31.4%, p < 0.001) and men (49.1%, p < 0.001). CONCLUSIONS: Lymphadenopathy is associated with a wide range of disorders; however, metastatic lymph nodes of malignancies are the most common cause for enlarged lymph nodes. PMID- 27182675 TI - Value of Ki-67 and computed tomography in the assessment of peripheral lung adenocarcinoma. AB - PURPOSE: This study was designed to determine whether proliferation antigen Ki-67 and/or a computed tomography (CT) value could be used to evaluate the clinical pathological features of peripheral lung adenocarcinoma. MATERIALS AND METHODS: A total of 116 eligible lung cancer patients were enrolled. Nodule size, lymph node metastasis, differentiation, Ki-67 expression and CT findings were assessed. The relationship between clinic parameters and the CT feature was analysed statistically. RESULTS: The percentage of lesions that had ground-glass opacity or localised air bronchogram was significantly greater in low CT value group (<30, p < 0.05). No significant association was observed between CT value and size in the subgroup with CT value > 0 (p = 0.66). As a proliferative marker of lung cancer, Ki-67 was present in a total of 115 (99.9%) of the 116 evaluable primary lung cancers. There was a statistically significant correlation between the Ki-67 index and CT value (p < 0.05). Compared to CT value, Ki-67 index possessed higher sensitivity to predict the differentiation and lymph node metastasis of peripheral lung adenocarcinoma, adding of CT value would enhance its specificity. CONCLUSION: Combination of Ki-67 expression and CT value determination was useful for the classification of differentiation and metastatic or proliferative potential of peripheral lung adenocarcinoma. PMID- 27182676 TI - Intrafamilial transmission of Helicobacter pylori: genotyping of faecal samples. AB - BACKGROUND: After more than 20 years of research, there is a little information about the detailed routes of Helicobacter pylori transmission. The aim of this study was to explore intrafamilial transmission of H. pylori in children who had indication for upper gastrointestinal endoscopy and their parents. METHODS: Children (aged up to 15 years) were studied during September 2012 to October 2013. The parents of those with positive urea breath test results were asked to provide faecal and blood samples after giving informed consent. Non-invasive tests such as immunoassay for serological antibodies against H. pylori and detection of its antigen in faeces were measured. The genetic similarity of the family strains was investigated by the random amplification of polymorphic DNA (RAPD-PCR) genotyping method. RESULTS: According to the genotyping results of 30 families, in 10 (33.3%) children related H. pylori genotypes to their mothers were found, while only 2 children (6.7%) had similar genotypes to their fathers. Interestingly, children with similar H. pylori genotype with their mothers had higher IgA (35.7 +/- 10.8) and IgM antibody titres (87.23 +/- 19.15) than other children. In addition, in these children, lower titres of IgG antibodies (9.93 +/ 3.31) were found rather than children who had no H. pylori in their faeces or had no similarities with their parents (30.28 +/- 6.15). CONCLUSIONS: In conclusion, mother-to-child transmission is the main route of intrafamilial transmission of H. pylori in Iranian families. Molecular typing of H. pylori can be useful in identifying a high-risk population. PMID- 27182678 TI - Letter to the Editor: Antimicrobial properties of mucus from the brown garden snail Helix aspersa. PMID- 27182677 TI - Antifungal effect of Echinophora platyloba on expression of CDR1 and CDR2 genes in fluconazole-resistant Candida albicans. AB - BACKGROUND: Several studies examined the effect of the Echinophora platyloba extract in treatment of azole-resistant Candida albicans clinical isolates. OBJECTIVE: We investigated the effect of E. platyloba extract on expression of CDR1 and CDR2 genes in fluconazole-resistant clinical isolates of C. albicans using real-time PCR. MATERIALS AND METHODS: The crude extract of E. platyloba was obtained using percolation method. Using serial dilution method, different concentrations of extract were achieved. Two hundred microlitres of fungal suspension (10(6) CFU/ml) was added to the media and cultured with different concentrations and then incubated at 37 degrees C for 48 h. The concentration of extract in the first tube, which inhibited the growth of C. albicans, was recorded as the Minimal Inhibitory Concentration (MIC). In order to analyse the expression of CDR1 and CDR2 genes, RNA was extracted from C. albicans isolates before and after treatment with MIC of E. platyloba using glass beads and the denaturing buffer agents in an RNase-free environment and then the cDNA was synthesised and used for real-time PCR assay. RESULTS: Twenty of total of 148 isolates were resistant to fluconazole. The MIC and MFC for the alcoholic extract of E. Platyloba were 64 mg/ml and 128 mg/ml, respectively. Real-time PCR results revealed that the mRNA levels of CDR1 and CDR2 genes significantly declined after incubation with E. Platyloba (both p values < 0.001). CONCLUSION: E. Platyloba is effective in reducing CDR1 and CDR2 expression which in turn plays an important role in fluconazole resistance in Candida species. PMID- 27182680 TI - High-Speed Resistance Training in Older Women: The Role of Supervision. AB - Older women participated in a 12-week high-speed resistance training program under two supervisor-to-subject ratio methods (i.e., high versus low supervision) to assess its effects on muscle strength, power, functional performance, and quality of life assessed before (T1) and after (T2) intervention. Women were divided into either the control group (CG, n = 15), high supervision group (HSG, n = 30), or low supervision group (LSG, n = 28). The training program included exercises requiring high-speed concentric muscle actions. No differences were observed among groups at T1. Between T1 and T2, the HSG showed a higher (p < .05) improvement in muscle strength (ES = 0.36-1.26), power (ES = 0.5-0.88), functional performance (ES = 0.52-0.78), and quality of life (ES = 0.44-0.82) compared with LSG and CG. High-speed resistance training under closer supervision is more effective for improving muscle strength, power, functional performance, and quality of life in older women. PMID- 27182681 TI - The Discrepancy between Performance-Based Measures and Questionnaires when Assessing Clinical Outcomes and Quality of Life in Pediatric Patients with Neurological Disorders. AB - In clinical outcome assessment, the relation between performance-based measures and questionnaire ratings of the same domain is weak, but correlations between questionnaires proposed for the evaluation of different domains are strong. The present study aims to illustrate these phenomena in a group of patients with neurofibromatosis type 1 (NF1) and to propose an explanatory hypothesis. A single neuropsychologist interviewed the parents about the child's situation and current difficulties and then assessed this parental view as overall positive or overall negative. The same assessor then administered the Wechsler Intelligence Scales and neuropsychological tests to 78 children and adolescents with NF1 (5-18 years). Parents then completed the Child Behavioral Checklist (CBCL), the Conners' Parent Rating Scale, the Behavior Rating Inventory of Executive Function (BRIEF), as well as questionnaires assessing quality of life, impact of the medical disorder, and their own difficulties. All questionnaires were inter correlated (r = 0.29 - 0.84) and associated with the overall positive or negative parental view of the child's progress (effect size = 0.41-1.46). Conversely, questionnaires were weakly or not significantly related to intelligence, cognitive measures, or clinical severity. In conclusion, the parental view of the child's progress was related to the answers to questionnaires assessing quality of life or strengths and difficulties of patients with a neurological disorder. This factor should be assessed independently and taken into account when assessing clinical outcome. PMID- 27182679 TI - Hemodiafiltration With Endogenous Reinfusion Improved Microinflammation and Endothelial Damage Compared With Online-Hemodiafiltration: A Hypothesis Generating Study. AB - Hemodiafiltration with endogenous reinfusion (HFR) after ultrafiltrate passage through a resin cartridge combines adsorption, convection, and diffusion. Our prospective single-center crossover study compared HFR and online hemodiafiltration (OLHDF) effects on two uremic toxins and 13 inflammatory, endothelial status, or oxidative stress markers. After an 8-week run-in period of high-flux hemodialysis, 17 eligible stable dialysis patients (median age 65 years, 10 male) without overt clinical inflammation were scheduled for four 8 week periods in the sequence: HFR/OLHDF/HFR/OLHDF. Relative to OLHDF, HFR was associated with greater indoxyl sulfate removal and lesser abnormalities in all other study variables, namely circulating interleukin-6, tumor necrosis factor alpha, proportions of activated proinflammatory (CD14+CD16+, CD14++CD16+) monocytes, endothelial progenitor cells, apoptotic endothelial microparticles, vascular endothelial growth factor, vascular cellular adhesion molecule, angiopoietins 2 and 1, annexin V, and superoxide dismutase. Differences were significant (P < 0.05) in median values of 13/15 variables. Study period comparisons were generally consistent with dialysis technique comparisons, as were data from the subgroup completing all study periods (n = 9). Our investigation provides hypothesis-generating results suggesting that compared with OLHDF, HFR improves protein-bound toxin removal, inflammatory and endothelial status, and oxidative stress. PMID- 27182682 TI - Pharmacokinetics and tissue distribution of ginkgolide A, ginkgolide B, and ginkgolide K after intravenous infusion of ginkgo diterpene lactones in a rat model. AB - Ginkgo diterpene lactones are compounds that are extracted from the Ginkgo biloba leaf and possess pharmacologic activities with neuroprotective effects. To address the poor bioavailability of ginkgo diterpene lactones, ginkgo diterpene lactone meglumine injection (GDLI) was formulated and is commercially available. In this study, a simple, sensitive and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for assessing the total amount and the amount of the prototype forms of ginkgolides A (GA), B (GB) and K (GK) in rat plasma and tissues. This method was used to calculate the concentrations of the hydrolysed carboxylic forms and assess the pharmacokinetics of the ginkgolides after intravenous (i.v.) GDLI administration in rats. Generally, all three ginkgolide forms showed dose-dependent plasma concentrations, and no obvious differences in pharmacokinetic parameters, i.e., area under the curve (AUC) of plasma concentration versus time and half-life, were observed after GDLI administration on 7 consecutive days. These ginkgolides primarily existed in the carboxylic form in the plasma, and the systemic concentrations of the carboxylic forms of GA and GB were 11- to 17- and 3- to 4 fold higher than those of their prototype forms, respectively. In contrast, dramatically increased levels of the GA and GB prototype lactones were detected in the liver and heart. GA, GB, and GK were extensively distributed in various organs/tissues; the highest levels were found in the kidneys, liver, and intestine, and the lowest levels were found in the brain. These data suggest that ginkgolides have difficulty crossing the blood-brain barrier and that their targets for protecting against cerebral ischaemia are located outside the central system. PMID- 27182683 TI - Anionic Lipid Content Presents a Barrier to the Activity of ROMP-Based Synthetic Mimics of Protein Transduction Domains (PTDMs). AB - Many biophysical studies of protein transduction domains (PTDs) and their synthetic mimics (PTDMs) focus on the interaction between the polycationic PTD(M) and anionic phospholipid surfaces. Most, but not all, of these studies suggest that these cation-anion interactions are vital for membrane activity. In this study, the effect of anionic lipid content on PTDM performance was examined for three ring-opening metathesis (ROMP)-based PTDMs with varying hydrophobicity. Using a series of dye-loaded vesicles with gradually increasing anionic lipid content, we saw that increased anionic lipid content inhibited dye release caused by these PTDMs. This result is the opposite of what was found in studies with poly- and oligo-arginine. While the effect is reduced for more hydrophobic PTDMs, it is observable even with the most hydrophobic PTDMs of our test panel. Additional experiments included dynamic light scattering and zeta potential measurements to measure size as a function of vesicle surface charge in the presence of increasing PTDM concentration and surface plasmon resonance spectroscopy to quantify binding between PTDMs and surface-bound lipid layers with varying anion content. The results from these measurements suggested that PTDM hydrophobicity, not cation-anion interactions, is the main driving force of the interaction between our PTDMs and the model membranes investigated. This suggests a model of interaction where surface association and membrane insertion are driven by PTDM hydrophobicity, while anionic lipid content serves primarily to "pin" the PTDM to the membrane surface and limit insertion. PMID- 27182684 TI - Thermodynamic Integration Networks and Their Application to Charge Transfer Reactions within the AauDyPI Fungal Peroxidase. AB - We present a computer simulation study of the thermodynamics and kinetics of charge transfer reactions within the fungal peroxidase AauDyPI from Auricularia auriculae-judae. Driving forces and reorganization energies are obtained from a thermodynamic integration scheme based upon molecular dynamics simulations. To enhance the numerical accuracy, the free energies are analyzed within a least squares scheme of a closely knit thermodynamic network. We identify Tyr147, Tyr229, and Trp105 as oxidative agents, and find Trp377 to be a long-lived reaction intermediate. The results are compared to recent experimental findings. PMID- 27182685 TI - Cancer heterogeneity and drug metabolism: what we know and what we need to know. PMID- 27182686 TI - Impact of the activity calculation method used in transarterial radioembolization: a dosimetric comparison between 90Y-SIRSphere and 90Y TheraSphere therapy. AB - PURPOSE: Transarterial radioembolization is used to treat primary and secondary liver malignancies. Two commercially available drugs are utilized for the purpose. The aim of our study is to compare the radiation dose delivered to the tumor by these drugs. MATERIALS AND METHODS: This study included 86 patients (M : F - 7.6 : 1, median age=50.5 years), 46 patients were treated by Y-TheraSphere and 42 patients were treated by Y-SIRSphere. Activity administered in Y TheraSphere and Y-SIRSphere was calculated using a modified partition model and a modified body surface area model, respectively. The radiation dose delivered by two drugs was calculated and compared in our study. RESULT: Activity administered in Y-TheraSphere was significantly higher than that of Y-SIRSphere. Hence, the radiation dose delivered to the tumor by Y-SIRSphere was significantly lower (58.4%) than that of Y-TheraSphere (P=0.000). CONCLUSION: As the radiation dose delivered by Y-SIRSphere was lower than Y-TheraSphere, we believe that the formula for Y-SIRSphere activity calculation needs to be modified so that the optimal dose can be delivered to the tumor. PMID- 27182687 TI - D-Dimer predicts prognosis and non-resectability in patients with pancreatic cancer: a prospective cohort study. AB - To examine the impact of plasma D-dimer levels in predicting 3-year survival and nonresectability in pancreatic cancer patients. Ninety-five patients were divided into three groups according to plasma D-dimer levels. Kaplan-Meier survival curves and hazard ratios were computed, and diagnostic indices of D-dimer in the prediction of resectability were assessed. The median survival among patients with low, medium and high D-dimer levels was 13.7 [95% confidence interval (CI): 10.2-19.6], 6.2 (95% CI: 2.0-15.1) and 2.4 months (95% CI: 1.4-3.3), respectively. The adjusted hazard ratio of death in the group of patients with high D-dimer levels was 2.2 (95% CI: 1.1-4.2). The positive and negative predictive values of D-dimer in the prediction of nonresectability were 89% (95% CI: 77-96%) and 48% (95% CI: 33- 63%), respectively. An elevated D-dimer level is associated with reduced survival in pancreatic cancer and predicts nonresectability. PMID- 27182688 TI - Haemostatic balance in cirrhosis. AB - Despite the prolongation of coagulation tests, recent studies reported an increased frequency of thromboembolic events in patients with cirrhosis. The aim of this study was to evaluate the haemostatic balance in cirrhotic patients through assessing the variation of pro- and anticoagulant factors and evaluating the in-vitro thrombin generation in patients with cirrhosis and in healthy patients. Fifty-one cirrhotic patients with or without thromboembolic events and 50 controls matched by age and sex were enrolled. Procoagulant (factors VII, II, V, VIII, and XII) and inhibitor (protein C, protein S and antithrombin) factor activities were determined. Thrombin generation was measured as endogenous thrombin potential (ETP). Haemostatic balance was assessed by means of both procoagulant to inhibitor coagulation factor ratios and ETP with to without protein C activation ratios. There were 24 males and 27 females. The mean age was 57.8 years [16-91 years]. Pro and anticoagulant factors were significantly lower in patients than in controls (P < 0.001) except for factor VIII and protein S. In fact factor VIII level was significantly higher in patients than in controls and protein S levels were not significantly different between patients and controls. Almost all the pro to anticoagulant factor ratios were higher in cirrhotics than in controls, especially the factor VIII to protein C ratios which increased significantly from Child Pugh A to C (P < 0.001), the ratio of ETP with to without protein C activator was higher in patients than in controls, but did not reach a significant level (0.8 vs. 0.52) There was no statistically significant difference between Child classes. When comparing patients with history of thrombosis (n = 7) to those matched by age and sex and without history of thrombosis (n = 14), the ratios were not statistically different between the two groups. Haemostatic changes in cirrhosis tend to rebalance the haemostatic system. This state often results in a hypercoagulable state attested by increased pro- to anticoagulant factor ratios and a normal thrombin generation. PMID- 27182689 TI - Prognostic factors for seizure outcome in patients with MRI-negative temporal lobe epilepsy: A meta-analysis and systematic review. AB - PURPOSE: To perform a systematic review and meta-analysis to identify predictors of postoperative seizure freedom in patients with magnetic resonance imaging (MRI)-negative temporal lobe epilepsy. METHOD: Publications were screened from electronic databases (MEDLINE, EMBASE), epilepsy archives, and bibliographies of relevant articles that were written in English. We recorded all possible risk factors that might predict seizure outcome after surgery. We calculated odds ratio (OR) with corresponding 95% confidence intervals (95% CI) of predictors for postoperative seizure freedom. Heterogeneity was assessed with I(2). All meta analyses were performed using Review Manager. RESULTS: Epilepsy duration (OR=2.57, 95% CI=1.21-5.47, p<0.05, I(2)=1%) and ictal or interictal electroencephalographic anomalies precisely localized in the ipsilateral temporal lobe (OR=3.89, 95% CI=1.66-9.08, p<0.01, I(2)=0 and OR=3.38, 95% CI=1.57-7.25, p<0.05, I(2)=0, respectively) were significantly associated with a higher rate of seizure freedom after surgery. However, the positron emission tomography (PET) results were not predictive of postoperative seizure freedom (OR=2.11, 95% CI=0.95-4.65, p=0.06, I(2)=0). No significant difference in seizure freedom was observed between the positive and negative pathology groups (OR=1.36, 95% CI=0.70 2.63, p=0.36, I(2)=0). CONCLUSIONS: A shorter epilepsy duration and scalp electroencephalogram (EEG) signals localized precisely in the temporal lobe predicted a better seizure outcome in patients with MRI-negative temporal lobe epilepsy. PMID- 27182690 TI - Ultrafast Exciton Hopping Observed in Bare Semiconducting Carbon Nanotube Thin Films with Two-Dimensional White-Light Spectroscopy. AB - We observe ultrafast energy transfer between bare carbon nanotubes in a thin film using two-dimensional (2D) white-light spectroscopy. Using aqueous two-phase separation, semiconducting carbon nanotubes are purified from their metallic counterparts and condensed into a 10 nm thin film with no residual surfactant. Cross peak intensities put the time scale for energy transfer at <60 fs, and 2D anisotropy measurements determine that energy transfer is most efficient between parallel nanotubes, thus favoring directional energy flow. Lifetimes are about 300 fs. Thus, these results are in sharp contrast to thin films prepared from nanotubes that are wrapped by polymers, which exhibit picosecond energy transfer and randomize the direction of energy flow. Ultrafast energy flow and directionality are exciting properties for next-generation photovoltaics, photodetectors, and other devices. PMID- 27182691 TI - Changes in Corneal Thickness and Specular Microscopic Indices in Acute Unilateral Anterior Uveitis. AB - PURPOSE: To compare central corneal thickness (CCT) and specular microscopic indices in active unilateral anterior uveitis with the same indices 1 week after the initiation of treatment. METHODS: This study included 30 eyes with active unilateral idiopathic anterior uveitis. CCT and specular microscopic indices were compared before and after 1 week of the treatment with topical medications. RESULTS: At the first visit, mean CCT was significantly greater in affected eyes (mean +/- standard deviation: 514.0 +/- 23.0) than in fellow eyes (493.2 +/- 10.6) (p < 05). There was a significant decrease in CCT of the involved eye 1 week after start of treatment to 494.1 +/- 23.1 MUm (p < 05). No significant differences were observed in the specular microscopic indices between the affected and fellow eyes before treatment and 1 week after the treatment. CONCLUSION: We found that eyes with unilateral active anterior uveitis had increased CCT in comparison to their healthy fellow eyes without a change in the specular microscopic indices. PMID- 27182692 TI - Pancreatic duct guidewire placement for biliary cannulation for the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. AB - BACKGROUND: Difficult cannulation is a risk factor for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). It has been postulated that the pancreatic duct guidewire (PGW) technique may improve biliary cannulation success and reduce the risk of PEP in people with difficult cannulation. OBJECTIVES: To systematically review evidence from randomised controlled trials (RCTs) assessing the effectiveness and safety of the PGW technique compared to persistent conventional cannulation (CC) (contrast- or guidewire-assisted cannulation) or other advanced techniques in people with difficult biliary cannulation for the prevention of PEP. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and CINAHL databases, major conference proceedings, and for ongoing trials on the ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) up to March 2016, using the Cochrane Upper Gastrointestinal and Pancreatic Diseases model with no language restrictions. SELECTION CRITERIA: RCTs comparing the PGW technique versus persistent CC or other advanced techniques in people undergoing ERCP with difficult biliary cannulation. DATA COLLECTION AND ANALYSIS: Two review authors independently conducted study selection, data extraction, and methodological quality assessment. Using intention-to-treat analysis with random-effects models, we combined dichotomous data to obtain risk ratios (RR) with 95% confidence intervals (CI). We assessed heterogeneity using the Chi(2) test (P < 0.15) and I(2) test (> 25%). To explore sources of heterogeneity, we conducted a priori subgroup analyses according to trial design, use of pancreatic duct (PD) stent, involvement of trainees in cannulation, publication type, and risk of bias. To assess the robustness of our results, we carried out sensitivity analyses using different summary statistics (RR versus odds ratio (OR)) and meta-analytic models (fixed-effect versus random-effects). MAIN RESULTS: We included seven RCTs comprising 577 participants. There was no significant heterogeneity among trials for the outcome of PEP (P = 0.32; I(2) = 15%). The PGW technique significantly increased PEP compared to other endoscopic techniques (RR 1.98, 95% CI 1.14 to 3.42; low-quality evidence). The number needed to treat for an additional harmful outcome was 13 (95% CI 5 to 89). Among the three studies that compared the PGW technique with persistent CC, the incidence of PEP was 13.5% for the PGW technique and 8.7% for persistent CC (RR 1.58, 95% CI 0.83 to 3.01; low-quality evidence). Among the two studies that compared the PGW technique with precut sphincterotomy, the incidence of PEP was 29.8% in the PGW group versus 10.3% in the precut group (RR 2.92, 95% CI 1.24 to 6.88; low-quality evidence). Among the two studies that compared the PGW technique with PD stent placement, the incidence of PEP was 11.7% for the PGW technique and 5.0% for PD stent placement (RR 1.75, 95% CI 0.08 to 37.50; very low-quality evidence). There was no significant difference in common bile duct (CBD) cannulation success with the randomised technique (RR 1.04, 95% CI 0.87 to 1.24; low-quality evidence) or overall CBD cannulation success (RR 1.04, 95% CI 0.91 to 1.18; low-quality evidence) between the PGW technique and other endoscopic techniques. There was also no statistically significant difference in the risk of other ERCP-related complications (bleeding, perforation, cholangitis, and mortality). The results were robust in sensitivity analyses. The overall quality of evidence for the outcome of PEP was low or very low because of study limitations and imprecision. AUTHORS' CONCLUSIONS: In people with difficult CBD cannulation, sole use of the PGW technique appears to be associated with an increased risk of PEP. Prophylactic PD stenting after use of the PGW technique may reduce the risk of PEP. However, the PGW technique is not superior to persistent attempts with CC, precut sphincterotomy, or PD stent in achieving CBD cannulation. The influence of co-intervention in the form of rectal peri-procedural nonsteroidal anti inflammatory drug administration is unclear. PMID- 27182693 TI - Different types of implants for reconstructive breast surgery. AB - BACKGROUND: Breast cancer is the most common cancer in women worldwide, and is a leading cause of cancer death among women. Prophylactic or curative mastectomy is often followed by breast reconstruction for which there are several surgical approaches that use breast implants with which surgeons can restore the natural feel, size and shape of the breast. OBJECTIVES: To assess the effects of different types of breast implants on capsular contracture, surgical short- and long-term complications, postoperative satisfaction level and quality of life in women who have undergone reconstructive breast surgery after mastectomy. SEARCH METHODS: We searched the Cochrane Breast Cancer Group's Specialised Register on 20 July 2015, MEDLINE (1985 to 20 July 2015), EMBASE (1985 to 20 July 2015) and the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 8, 2015). We also searched the World Health Organization's International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov on 16 July 2015. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs that compared different types of breast implants for reconstructive surgery. We considered the following types of intervention: implant envelope surfaces - texturised versus smooth; implant filler material - silicone versus saline, PVP Hydrogel versus saline; implant shape - anatomical versus round; implant volume - variable versus fixed; brands - different implant manufacturing companies and implant generation (fifth versus previous generations). DATA COLLECTION AND ANALYSIS: Two review authors independently assessed methodological quality and extracted data. We used standard Cochrane methodological procedures. The quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. MAIN RESULTS: Five RCTs with 202 participants met the inclusion criteria. The women participants were typically in their 50s, and the majority of them (about 82%) received reconstructive surgery following breast cancer, while the others had reconstructive surgery after prophylactic mastectomy. The studies were heterogenous in terms of implant comparisons, which prevented us from pooling the data.The studies were judged as being at an unclear risk of bias for most risk of bias items owing to poor quality of reporting in the trial publications. Three of the five RCTs were judged to be at high risk of attrition bias, and one at high risk of detection bias.Textured silicone versus smooth silicone implants: textured implants were associated with worse outcomes when compared to smooth implants (capsular contracture: risk ratio (RR) 0.82, 95% CI 0.14 to 4.71; 1 study, 20 participants; very low quality evidence; reintervention: RR 0.82, 95% CI 0.14 to 4.71; 1 study, 20 participants; very low quality evidence). No results in this comparison were statistically significant.Silicone versus saline implants: saline-filled implants performed better than silicone-filled implants for some outcomes; specifically, they produced less severe capsular contracture (RR 3.25, 95% CI 1.24 to 8.51; 1 study, 60 participants; very low quality evidence) and increased patient satisfaction (RR 0.60, 95% CI 0.41 to 0.88; 1 study, 58 participants; very low quality evidence). However reintervention was significantly more frequent in the saline-filled implant group than in the silicone-filled group (OR 0.08, 95% CI 0.01 to 0.43; 1 study, 60 participants; very low quality evidence).Poly(N-vinyl-2 pyrrolidone) hydrogel-filled (PVP-hydrogel) versus saline-filled implants: PVP hydrogel-filled implants were associated with worse outcomes when compared to saline-filled implants (capsular contracture: RR 3.50, 95% CI 0.83 to 14.83; 1 study, 40 participants; very low quality evidence; short-term complications: RR 2.10, 95% CI 0.21 to 21.39; 1 study, 41 participants; very low quality evidence).Anatomical versus round implants: anatomical implants were associated with worse outcomes than round implants (capsular contracture: RR 2.00, 95% CI 0.20 to 20.15; 1 study, 36 participants; very low quality evidence; short-term complications: RR 2.00, 95% CI 0.42 to 9.58; 1 study, 36 participants; very low quality evidence; reintervention: RR 1.50, 95% CI 0.51 to 4.43; 1 study, 36 participants; very low quality evidence). No results in this comparison were statistically significant.Variable-volume versus fixed-volume implants: data about one-stage reconstruction using variable-volume implants were compared with data about fixed-volume implants positioned during the second surgical procedure of two-stage reconstructions. Fixed-volume implant reconstructions were possibly associated with a greater number of women reporting that their reconstruction corresponded with expected results (RR 0.25, 95% CI 0.10 to 0.62; 1 study, 40 participants; very low quality evidence) and fewer reinterventions (RR 7.00, 95% CI 1.82 to 26.89; 1 study, 40 participants; very low quality evidence) when compared to variable-volume implants. A higher patient satisfaction level (rated from 1 to 6, with 1 being very bad and 6 being very good) was found with the fixed-volume implants for overall aesthetic result (mean difference (MD) -1.10, 95% CI -1.59 to -0.61; 1 study, 40 participants; very low quality evidence).There were no studies that examined the effects of recent (fifth) generation silicone implants versus previous generations or different implant manufacturing companies. AUTHORS' CONCLUSIONS: Despite the central role of breast reconstruction in women with breast cancer, the best implants to use in reconstructive surgery have been studied rarely in the context of RCTs. Furthermore the quality of these studies and the overall evidence they provide is largely unsatisfactory. Some of our results can be interpreted as early evidence of potentially large differences between different surgical approaches, which should be confirmed in new high-quality RCTs that include a larger number of women. These days - even after a few million women have had breasts reconstructed - surgeons cannot inform women about the risks and complications of different implant-based breast reconstructive options on the basis of results derived from RCTs. PMID- 27182695 TI - PADI4 Polymorphisms in Iranian Patients with Rheumatoid Arthritis. AB - AIM: Rheumatoid arthritis (RA) is a chronic autoimmune disease which affects many tissues and organs, but majorly attacks synovial joints. Beyond the major histocompatibility complex (MHC) genes, Peptidyl arginine deiminase type IV (PADI4) has been suggested to be associated with RA susceptibility. Evidence regarding the association of PADI4 single nucleotide polymorphisms (SNP) and RA is controversial, thus we conducted this large-scale case-control study to assess the association of rs874881 and rs11203367 PADI4 SNPs with susceptibility to RA. MATERIALS AND METHODS: Study population (including 665 RA patients and 392 sex-, age-, and ethnicity-matched healthy controls) were enrolled from Rheumatology Research Center of Tehran University of Medical Sciences, Shariati hospital. RESULTS: Allele or genotype frequencies of the investigated PADI4 SNPs were not different between RA patients and healthy subjects; genotypes (expressed as odds ratios) of rs11203367 [TT 0.98 (0.68-1.4), CT 0.93 (0.71-1.24), P value > 0.05] and rs874881 [CC 1.02 (0.71-1.46), CG (0.70-1.39), p value > 0.05] did not affect RA risk. Disease severity score DAS28, RF and anti-CCP antibodies of RA patients were not different between various genotypes of PADI4 SNPs. CONCLUSIONS: These findings were similar for haplotypes and diplotypes of rs11203367 and rs874881 PADI4 SNPs. In conclusion, in this case-control study with sufficient sample size to detect associations, we observed that PADI4 SNPS rs11203367 and rs874881 do not significantly determine RA susceptibility; which is in line with studies of some European populations. It seems RA pathogenesis might be different among various ethnicities, which encourage us to consider these differences in developing therapeutic interventions for management of patients. PMID- 27182694 TI - Health-related quality of life before and after head and neck squamous cell carcinoma: Analysis of the Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey linkage. AB - BACKGROUND: Understanding health-related quality of life (HRQOL) is crucial to providing high-quality survivorship care for patients with head and neck squamous cell carcinoma (HNSCC). Trends in and prognostic significance of HRQOL before and after HNSCC have not been well described. METHODS: HRQOL for older individuals with HNSCC was examined using the linked Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey database. Surveys assessing HRQOL from 5 years prediagnosis to 10 years postdiagnosis were included. HRQOL over time was modeled using multilevel linear regression with restricted cubic splines and was reported as either total HRQOL or change in HRQOL (denoted Delta). The association of prediagnosis HRQOL with survival was examined. RESULTS: In total, 1653 individuals were included; of these, 61% completed 1 survey, and 39% completed multiple surveys. Overall HRQOL decreased progressively until 13 months postdiagnosis, then recovered toward baseline between 2 and 5 years. However, after stratification by survival group, the postdiagnosis recovery was not observed. Individuals with shorter survival had lower HRQOL prediagnosis (<2-year survivors, 87.3; > 5-year survivors, 96.4; P = .004) with a steeper decline in HRQOL during diagnosis and treatment (<2-year survivors: Delta, -16.6; 95% confidence interval [CI], -23.8, -9.4; > 5-year survivors: Delta, -0.9; 95% CI, 1.8, 0.08). Radiotherapy and advanced stage were associated with greater declines in HRQOL during diagnosis and treatment (P < .001). Higher prediagnosis HRQOL was independently associated with improved overall survival (adjusted hazard ratio for 10-point increase, 0.91; 95% CI, 0.85-0.97). CONCLUSIONS: HRQOL declines before and after HNSCC, whereas any observed posttreatment recovery is likely an artifact of shorter survival among individuals with the lowest HRQOL. The prognostic implication of prediagnosis HRQOL may inform patient counseling. Cancer 2016;122:1861-70. (c) 2016 American Cancer Society. PMID- 27182696 TI - Wells Rule and d-Dimer Testing to Rule Out Pulmonary Embolism: A Systematic Review and Individual-Patient Data Meta-analysis. AB - BACKGROUND: The performance of different diagnostic strategies for pulmonary embolism (PE) in patient subgroups is unclear. PURPOSE: To evaluate and compare the efficiency and safety of the Wells rule with fixed or age-adjusted d-dimer testing overall and in inpatients and persons with cancer, chronic obstructive pulmonary disease, previous venous thromboembolism, delayed presentation, and age 75 years or older. DATA SOURCES: MEDLINE and EMBASE from 1 January 1988 to 13 February 2016. STUDY SELECTION: 6 prospective studies in which the diagnostic management of PE was guided by the dichotomized Wells rule and quantitative d dimer testing. DATA EXTRACTION: Individual data of 7268 patients; risk of bias assessed by 2 investigators with the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) tool. DATA SYNTHESIS: The proportion of patients in whom imaging could be withheld based on a "PE-unlikely" Wells score and a negative d dimer test result (efficiency) was estimated using fixed (<=500 ug/L) and age adjusted (age * 10 ug/L in patients aged >50 years) d-dimer thresholds; their 3 month incidence of symptomatic venous thromboembolism (failure rate) was also estimated. Overall, efficiency increased from 28% to 33% when the age-adjusted (instead of the fixed) d-dimer threshold was applied. This increase was more prominent in elderly patients (12%) but less so in inpatients (2.6%). The failure rate of age-adjusted d-dimer testing was less than 3% in all examined subgroups. LIMITATION: Post hoc analysis, between-study differences in patient characteristics, use of various d-dimer assays, and limited statistical power to assess failure rate. CONCLUSION: Age-adjusted d-dimer testing is associated with a 5% absolute increase in the proportion of patients with suspected PE in whom imaging can be safely withheld compared with fixed d-dimer testing. This strategy seems safe across different high-risk subgroups, but its efficiency varies. PRIMARY FUNDING SOURCE: None. PMID- 27182697 TI - Epidemiology of Clostridium difficile Infection-Associated Reactive Arthritis in Children: An Underdiagnosed, Potentially Morbid Condition. AB - IMPORTANCE: The incidence of Clostridium difficile infection has increased among children. The epidemiology of pediatric C difficile infection-associated reactive arthritis is poorly understood. OBJECTIVE: To characterize the incidence, recognition, and distinguishing clinical features of pediatric C difficile infection-associated reactive arthritis among children with C difficile infection. DESIGN, SETTING, AND PARTICIPANTS: In this cohort and nested case control study using electronic health records from January 1, 2004, to December 31, 2013, across 3 geographically diverse pediatric health care networks, we screened for reactive arthritis among 148 children between ages 2 and 21 years with diagnostic or procedural codes suggesting musculoskeletal disease associated with C difficile diagnosis or positive testing. We identified 26 cases with acute arthritis or tenosynovitis within 4 weeks before to 12 weeks after confirmed C difficile infection with (1) no alternative explanation for arthritis and (2) negative synovial cultures (if obtained). Network-matched C difficile-infected controls without arthritis were randomly selected at the time of cohort member C difficile infections. MAIN OUTCOMES AND MEASURES: Incidence of C difficile infection-associated reactive arthritis was calculated based on (1) pediatric source population and (2) children with C difficile infection. Characteristics of cases and controls were compared using conditional logistic regression. RESULTS: Based on the cases identified within the source population of the 3 hospital networks, we estimated that C difficile infection-associated reactive arthritis incidence was 5.0 cases per million person-years (95% CI, 3.0-7.8). Reactive arthritis affected 1.4% of children with C difficile infection yearly (95% CI 0.8%-2.3%). Joint symptoms began a median of 10.5 days after initial gastrointestinal symptoms, often accompanied by fever (n = 15 [58%]) or rash (n = 14 [54%]). Only 35% of cases of C difficile infection-associated reactive arthritis were correctly diagnosed by treating health care professionals (range across centers, 0%-64%). Five affected children (19%) were treated for presumed culture-negative septic hip arthritis despite having prior postantibiotic diarrhea and/or other involved joints. Compared with controls, cases of C difficile infection-associated reactive arthritis were less likely to have underlying chronic conditions (odds ratio [OR], 0.3; 95% CI, 0.1-0.8). Although all cases had community-onset C difficile infection and fewer comorbidities, they were more likely to be treated in emergency departments and/or hospitalized (OR, 7.1; 95% CI, 1.6-31.7). CONCLUSIONS AND RELEVANCE: C difficile infection associated reactive arthritis is an underdiagnosed, potentially morbid reactive arthritis associated with C difficile infection occasionally misdiagnosed as septic arthritis. Given the rising incidence of pediatric C difficile infections, better recognition of its associated reactive arthritis is needed. PMID- 27182698 TI - Degradation Parameters from Pulse-Chase Experiments. AB - Pulse-chase experiments are often used to study the degradation of macromolecules such as proteins or mRNA. Considerations for the choice of pulse length include the toxicity of the pulse to the cell and maximization of labeling. In the general case of non-exponential decay, varying the length of the pulse results in decay patterns that look different. Analysis of these patterns without consideration to pulse length would yield incorrect degradation parameters. Here we propose a method that constructively includes pulse length in the analysis of decay patterns and extracts the parameters of the underlying degradation process. We also show how to extract decay parameters reliably from measurements taken during the pulse phase. PMID- 27182699 TI - A Toolbox for Quantitative Gene Expression in Varroa destructor: RNA Degradation in Field Samples and Systematic Analysis of Reference Gene Stability. AB - Varroa destructor is the major pest of Apis mellifera and contributes to the global honey bee health crisis threatening food security. Developing new control strategies to combat Varroa will require the application of molecular biology, including gene expression studies by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Both high quality RNA samples and suitable stable internal reference genes are required for accurate gene expression studies. In this study, ten candidate genes (succinate dehydrogenase (SDHA), NADH dehydrogenase (NADH), large ribsosmal subunit, TATA-binding protein, glyceraldehyde-3-phosphate dehydrogenase, 18S rRNA (18S), heat-shock protein 90 (HSP90), cyclophilin, alpha-tubulin, actin), were evaluated for their suitability as normalization genes using the geNorm, Normfinder, BestKeeper, and comparative DeltaCq algorithims. Our study proposes the use of no more than two of the four most stable reference genes (NADH, 18S, SDHA and HSP90) in Varroa gene expression studies. These four genes remain stable in phoretic and reproductive stage Varroa and are unaffected by Deformed wing virus load. When used for determining changes in vitellogenin gene expression, the signal-to-noise ratio (SNR) for the relatively unstable genes actin and alpha-tubulin was much lower than for the stable gene combinations (NADH + HSP90 +18S; NADH + HSP90; or NADH). Using both electropherograms and RT-qPCR for short and long amplicons as quality controls, we demonstrate that high quality RNA can be recovered from Varroa up to 10 days later stored at ambient temperature if collected into RNAlater and provided the body is pierced. This protocol allows the exchange of Varroa samples between international collaborators and field sample collectors without requiring frozen collection or shipping. Our results make important contributions to gene expression studies in Varroa by proposing a validated sampling protocol to obtain high quality Varroa RNA and the validation of suitable reference genes for expression studies in this globally important pest. PMID- 27182701 TI - The Power of Heterogeneity: Parameter Relationships from Distributions. AB - Complex scientific data is becoming the norm, many disciplines are growing immensely data-rich, and higher-dimensional measurements are performed to resolve complex relationships between parameters. Inherently multi-dimensional measurements can directly provide information on both the distributions of individual parameters and the relationships between them, such as in nuclear magnetic resonance and optical spectroscopy. However, when data originates from different measurements and comes in different forms, resolving parameter relationships is a matter of data analysis rather than experiment. We present a method for resolving relationships between parameters that are distributed individually and also correlated. In two case studies, we model the relationships between diameter and luminescence properties of quantum dots and the relationship between molecular weight and diffusion coefficient for polymers. Although it is expected that resolving complicated correlated relationships require inherently multi-dimensional measurements, our method constitutes a useful contribution to the modelling of quantitative relationships between correlated parameters and measurements. We emphasise the general applicability of the method in fields where heterogeneity and complex distributions of parameters are obstacles to scientific insight. PMID- 27182700 TI - Rapid Acquisition of Linezolid Resistance in Methicillin-Resistant Staphylococcus aureus: Role of Hypermutation and Homologous Recombination. AB - BACKGROUND: We previously reported the case of a 64-year-old man with mediastinitis caused by Staphylococcus aureus in which the infecting bacterium acquired linezolid resistance after only 14 days treatment with linezolid. We therefore investigated relevant clinical isolates for possible mechanisms of this rapid acquisition of linezolid resistance. METHODS: Using clinical S. aureus isolates, we assessed the in vitro mutation rate and performed stepwise selection for linezolid resistance. To investigate homologous recombination, sequences were determined for each of the 23S ribosomal RNA (23S rRNA) loci; analyzed sequences spanned the entirety of each 23S rRNA gene, including domain V, as well as the 16S-23S intergenic spacer regions. We additionally performed next-generation sequencing on clinical strains to identify single-nucleotide polymorphisms compared to the N315 genome. RESULTS: Strains isolated from the patient prior to linezolid exposure (M5-M7) showed higher-level linezolid resistance than N315, and the pre-exposure strain (M2) exhibited more rapid acquisition of linezolid resistance than did N315. However, the mutation rates of these and contemporaneous clinical isolates were similar to those of N315, and the isolates did not exhibit any mutations in hypermutation-related genes. Sequences of the 23S rRNA genes and 16S-23S intergenic spacer regions were identical among the pre and post-exposure clinical strains. Notably, all of the pre-exposure isolates harbored a recQ missense mutation (Glu69Asp) with respect to N315; such a lesion may have affected short sequence recombination (facilitating, for example, recombination among rrn loci). We hypothesize that this mechanism contributed to rapid acquisition of linezolid resistance. CONCLUSIONS: Hypermutation and homologous recombination of the ribosomal RNA genes, including 23S rRNA genes, appear not to have been sources of the accelerated acquisition of linezolid resistance observed in our clinical case. Increased frequency of short sequence recombination may have resulted from a recQ variant in the infecting organism. PMID- 27182702 TI - Rethinking Dosing Regimen Selection of Piperaquine for Malaria Chemoprevention: A Simulation Study. AB - BACKGROUND: The combination of short-acting dihydroartemisinin and long-acting piperaquine (DP) is among the first-line therapies for the treatment of uncomplicated Plasmodium falciparum malaria. Population pharmacokinetic models of piperaquine (PQ) based on data from acute treatment of young children can be used to predict exposure profiles of piperaquine under different DP chemoprevention regimens. The purpose of our study was to make such predictions in young children. METHODS: Based on a prior population pharmacokinetic model of PQ in young Ugandan children, we simulated capillary plasma concentration-time profiles (including their variability) of candidate chemoprevention regimens for a reference population of 1-2 year olds weighing at least 11 kg. Candidate regimens that were tested included monthly administration of standard therapeutic doses, bimonthly dosing, and weekly dosing (with and without a loading dose). RESULTS: Once daily doses of 320 mg for three days (960 mg total) at the beginning of each month are predicted to achieve an average steady-state trough capillary piperaquine concentration of 35 ng/mL, with 60% achieving a level of 30 ng/mL or higher. In contrast, weekly dosing of 320 mg (i.e., 33% higher amount per month) is predicted to approximately double the average steady-state trough concentration, increase the percent of children predicted to achieve 30 ng/mL or higher (94%), while at the same time lowering peak concentrations. Exposure at steady-state, reached at approximately 3 months of multiple dosing, is expected to be approximately 2-fold higher than exposure following initial dosing, due to accumulation. A loading dose improves early exposure, thereby reducing the risk of breakthrough infections at the initiation of chemoprevention. CONCLUSIONS: Once weekly chemoprevention of DP predicts favourable exposures with respect to both trough and peak concentrations. These predictions need to be verified, as well as safety evaluated, in field-based clinical studies of young children. Simulations based on prior knowledge provide a systematic information-driven approach to evaluate candidate DP chemopreventive regimens for future trial designs. PMID- 27182703 TI - Cathepsin B-Deficient Mice Resolve Leishmania major Inflammation Faster in a T Cell-Dependent Manner. AB - A critical role for intracellular TLR9 has been described in recognition and host resistance to Leishmania parasites. As TLR9 requires endolysosomal proteolytic cleavage to achieve signaling functionality, we investigated the contribution of different proteases like asparagine endopeptidase (AEP) or cysteine protease cathepsins B (CatB), L (CatL) and S (CatS) to host resistance during Leishmania major (L. major) infection in C57BL/6 (WT) mice and whether they would impact on TLR9 signaling. Unlike TLR9-/-, which are more susceptible to infection, AEP-/-, CatL-/- and CatS-/- mice are as resistant to L. major infection as WT mice, suggesting that these proteases are not individually involved in TLR9 processing. Interestingly, we observed that CatB-/- mice resolve L. major lesions significantly faster than WT mice, however we did not find evidence for an involvement of CatB on either TLR9-dependent or independent cytokine responses of dendritic cells and macrophages or in the innate immune response to L. major infection. We also found no difference in antigen presenting capacity. We observed a more precocious development of T helper 1 responses accompanied by a faster decline of inflammation, resulting in resolution of footpad inflammation, reduced IFNgamma levels and decreased parasite burden. Adoptive transfer experiments into alymphoid RAG2-/-gammac-/- mice allowed us to identify CD3+ T cells as responsible for the immune advantage of CatB-/- mice towards L. major. In vitro data confirmed the T cell intrinsic differences between CatB-/- mice and WT. Our study brings forth a yet unappreciated role for CatB in regulating T cell responses during L. major infection. PMID- 27182704 TI - Effect of Antiplatelet Therapy on Acute Respiratory Distress Syndrome and Mortality in Critically Ill Patients: A Meta-Analysis. AB - BACKGROUND: Antiplatelet agents are commonly used for cardiovascular diseases, but their pleiotropic effects in critically ill patients are controversial. We therefore performed a meta-analysis of cohort studies to investigate the effect of antiplatelet therapy in the critically ill. METHODS: Nine cohort studies, retrieved from PubMed and Embase before November 2015, involving 14,612 critically ill patients and 4765 cases of antiplatelet users, were meta-analysed. The main outcome was hospital or 30-day mortality. Secondary outcome was acute respiratory distress syndrome (ARDS) or acute lung injury (ALI). Random- or fixed effect models were taken for quantitative synthesis of the data. RESULTS: Antiplatelet therapy was associated with decreased mortality (odds ratio (OR) 0.61; 95% confidence interval (CI), 0.52-0.71; I2 = 0%; P <0. 001) and ARDS/ALI (OR 0.64; 95% CI, 0.50-0.82; I2 = 0%; P <0. 001). In every stratum of subgroups, similar findings on mortality reduction were consistently observed in critically ill patients. CONCLUSIONS: Antiplatelet therapy is associated with reduced mortality and lower incidence of ARDS/ALI in critically ill patients, particularly those with predisposing conditions such as high-risk surgery, trauma, pneumonia, and sepsis. However, it remains unclear whether similar findings can be observed in the unselected and broad population with critical illness. PMID- 27182705 TI - Impact of Wild Loci on the Allergenic Potential of Cultivated Tomato Fruits. AB - Tomato (Solanum lycopersicum) is one of the most extensively consumed vegetables but, unfortunately, it is also able to induce allergic reactions. In the past, it has been shown that the choice of tomato cultivar significantly influenced the allergic reaction of tomato allergic subjects. In this study we investigated the allergenic potential of the cultivated tomato line M82 and of two selected lines carrying small chromosome regions from the wild species Solanum pennellii (i.e. IL7-3 and IL12-4). We evaluated the positive interactions of IgEs of allergic subjects in order to investigate the different allergenic potential of the lines under investigation. We used proteomic analyses in order to identify putative tomato allergens. In addition, bioinformatic and transcriptomic approaches were applied in order to analyse the structure and the expression profiles of the identified allergen-encoding genes. These analyses demonstrated that fruits harvested from the two selected introgression lines harbour a different allergenic potential as those from the cultivated genotype M82. The different allergenicity found within the three lines was mostly due to differences in the IgE recognition of a polygalacturonase enzyme (46 kDa), one of the major tomato allergens, and of a pectin methylesterase (34 kDa); both the proteins were more immunoreactive in IL7-3 compared to IL12-4 and M82. The observed differences in the allergenic potential were mostly due to line-dependent translational control or post-translational modifications of the allergens. We demonstrated, for the first time, that the introgression from a wild species (S. pennellii) in the genomic background of a cultivated tomato line influences the allergenic properties of the fruits. Our findings could support the isolation of favorable wild loci promoting low allergenic potential in tomato. PMID- 27182707 TI - My memories are important to me: Changes in autobiographical memory in amyotrophic lateral sclerosis. AB - OBJECTIVE: The loss of autobiographical memories (ABM) is a pervasive feature of neurodegenerative diseases. Studies to date have not investigated ABM retrieval in amyotrophic lateral sclerosis (ALS), a multisystem disorder that may be associated with cognitive dysfunction and dementia. METHOD: The integrity of autobiographical memory was evaluated in 22 ALS patients compared with 28 age matched controls using the Autobiographical Interview (AI), a semistructured interview assessing autobiographical events from discrete time periods across the life span. RESULTS: ABM retrieval was preserved in ALS and remained rich in detail for personal events in recent (last 12-months) and remote (teenage years) time epochs. ABM retrieval was positively correlated with months since ALS symptom onset, with a greater number of contextual details being recalled as ALS progressed. A shift in how ABMs were perceived in ALS patients became apparent, with more recurrent reflection of recent life, which was also weighted with greater personal importance. CONCLUSION: The preservation of ABM in ALS has clinical implications for the use of life review as a therapeutic tool in a multidisciplinary care setting. (PsycINFO Database Record PMID- 27182706 TI - Exome Sequencing Identifies a Novel LMNA Splice-Site Mutation and Multigenic Heterozygosity of Potential Modifiers in a Family with Sick Sinus Syndrome, Dilated Cardiomyopathy, and Sudden Cardiac Death. AB - The goals are to understand the primary genetic mechanisms that cause Sick Sinus Syndrome and to identify potential modifiers that may result in intrafamilial variability within a multigenerational family. The proband is a 63-year-old male with a family history of individuals (>10) with sinus node dysfunction, ventricular arrhythmia, cardiomyopathy, heart failure, and sudden death. We used exome sequencing of a single individual to identify a novel LMNA mutation and demonstrated the importance of Sanger validation and family studies when evaluating candidates. After initial single-gene studies were negative, we conducted exome sequencing for the proband which produced 9 gigabases of sequencing data. Bioinformatics analysis showed 94% of the reads mapped to the reference and identified 128,563 unique variants with 108,795 (85%) located in 16,319 genes of 19,056 target genes. We discovered multiple variants in known arrhythmia, cardiomyopathy, or ion channel associated genes that may serve as potential modifiers in disease expression. To identify candidate mutations, we focused on ~2,000 variants located in 237 genes of 283 known arrhythmia, cardiomyopathy, or ion channel associated genes. We filtered the candidates to 41 variants in 33 genes using zygosity, protein impact, database searches, and clinical association. Only 21 of 41 (51%) variants were validated by Sanger sequencing. We selected nine confirmed variants with minor allele frequencies <1% for family studies. The results identified LMNA c.357-2A>G, a novel heterozygous splice-site mutation as the primary mutation with rare or novel variants in HCN4, MYBPC3, PKP4, TMPO, TTN, DMPK and KCNJ10 as potential modifiers and a mechanism consistent with haploinsufficiency. PMID- 27182709 TI - Neuronal correlates of serial position performance in amnestic mild cognitive impairment. AB - OBJECTIVES: Delayed recall of the first words of a list-the primacy position-is thought to be particularly dependent on intact memory consolidation. Hippocampal volume has been suggested as the primary neuronal correlate of delayed primacy recall in cognitively normal elderly individuals. Here, we studied the association of hippocampal volume with primacy recall in individuals with amnestic mild cognitive impairment (aMCI). METHOD: We investigated serial position performance in 88 subjects with aMCI using a 16-word list (the California Verbal Learning Test [CVLT]). Primacy and recency performance were measured during learning and delayed recall. Hippocampal volumes were automatically determined from structural MRI scans. We conducted regression analyses with bilateral hippocampal volumes as predictors and serial position indices as outcomes. RESULTS: After controlling for age, gender, and total intracranial volume, bilateral hippocampal volume was not associated with primacy recall either during learning or delayed recall. Primacy performance during learning was associated with the right inferior and middle temporal gyrus as well as the right inferior parietal cortex and supramerginal gyrus. During delayed recall, primacy performance was related to the bilateral supramarginal gyri. CONCLUSIONS: Our findings suggest a reduced primacy effect in aMCI already during learning, contrasting previous findings in normal cognitive aging. This might indicate impaired encoding and consolidation processes at an early stage of episodic memory acquisition. Furthermore, our data indicate that hippocampal volume may not be a relevant determinant of residual primacy performance in the stage of aMCI, which may rather depend on temporal and parietal neocortical networks. (PsycINFO Database Record PMID- 27182708 TI - Adaptive functioning following pediatric traumatic brain injury: Relationship to executive function and processing speed. AB - OBJECTIVE: Pediatric traumatic brain injury (TBI) may affect children's ability to perform everyday tasks (i.e., adaptive functioning). Guided by the American Association for Intellectual and Developmental Disabilities (AAIDD) model, we explored the association between TBI and adaptive functioning at increasing levels of specificity (global, AAIDD domains, and subscales). We also examined the contributions of executive function and processing speed as mediators of TBI's effects on adaptive functioning. METHOD: Children (ages 8-13) with severe TBI (STBI; n = 19), mild-moderate TBI (MTBI; n = 50), or orthopedic injury (OI; n = 60) completed measures of executive function (TEA-Ch) and processing speed (WISC-IV) an average of 2.7 years postinjury (SD = 1.2; range: 1-5.3). Parents rated children's adaptive functioning (ABAS-II, BASC-2, CASP). RESULTS: STBI had lower global adaptive functioning (eta2 = .04-.08) than the MTBI and OI groups, which typically did not differ. Deficits in the STBI group were particularly evident in the social domain, with specific deficits in social participation, leisure, and social adjustment (eta2 = .06-.09). Jointly, executive function and processing speed were mediators of STBI's effects on global adaptive functioning and in conceptual and social domains. In the STBI group, executive function mediated social functioning, and processing speed mediated social participation. CONCLUSIONS: Children with STBI experience deficits in adaptive functioning, particularly in social adjustment, with less pronounced deficits in conceptual and practical skills. Executive function and processing speed may mediate the effects of STBI on adaptive functioning. Targeting adaptive functioning and associated cognitive deficits for intervention may enhance quality of life for pediatric TBI survivors. (PsycINFO Database Record PMID- 27182710 TI - A meta-analysis of working memory impairments in survivors of moderate-to-severe traumatic brain injury. AB - OBJECTIVES: To establish the magnitude of deficits in working memory (WM) and short-term memory (STM) in those with moderate-to-severe traumatic brain injury (TBI) relative to age-matched, healthy controls and to explore the moderating effects of time since injury and age at injury on these impairments. METHOD: Twenty-one studies that compared the WM and/or STM abilities of individuals with at least a moderate TBI relative to healthy controls were included in a random effects meta-analysis. Measures used to examine memory performance were categorized by modality (visuospatial, verbal) and memory system (WM, STM). RESULTS: Individuals with TBI had significant deficits in verbal STM (Cohen's d = .41), visuospatial WM (Cohen's d = .69), and verbal WM (Cohen's d = .37) relative to controls. Greater decrements in verbal STM and verbal WM skills were associated with longer time postinjury. Larger deficits were observed in verbal WM abilities in individuals with older age at injury. CONCLUSION: Evidence for WM impairments following TBI is consistent with previous research. Larger verbal STM and verbal WM deficits were related to a longer time postinjury, suggesting that these aspects of memory do not "recover" over time and instead, individuals might show increased rates of cognitive decline. Age at injury was associated with the severity of verbal WM impairments, with larger deficits evident for injuries that occurred later in life. Further research needs to chart the long-term effects of TBI on WM and to compare the effects of injury on verbal relative to visuospatial memory. (PsycINFO Database Record PMID- 27182711 TI - Recent Shift in Climate Relationship Enables Prediction of the Timing of Bird Breeding. AB - Large-scale climate processes influence many aspects of ecology including breeding phenology, reproductive success and survival across a wide range of taxa. Some effects are direct, for example, in temperate-zone birds, ambient temperature is an important cue enabling breeding effort to coincide with maximum food availability, and earlier breeding in response to warmer springs has been documented in many species. In other cases, time-lags of up to several years in ecological responses have been reported, with effects mediated through biotic mechanisms such as growth rates or abundance of food supplies. Here we use 23 years of data for a temperate woodland bird species, the great tit (Parus major), breeding in deciduous woodland in eastern England to demonstrate a time-lagged linear relationship between the on-set of egg laying and the winter index of the North Atlantic Oscillation such that timing can be predicted from the winter index for the previous year. Thus the timing of bird breeding (and, by inference, the timing of spring events in general) can be predicted one year in advance. We also show that the relationship with the winter index appears to arise through an abiotic time-lag with local spring warmth in our study area. Examining this link between local conditions and larger-scale processes in the longer-term showed that, in the past, significant relationships with the immediately preceding winter index were more common than those with the time-lagged index, and especially so from the late 1930s to the early 1970s. However, from the mid 1970s onwards, the time-lagged relationship has become the most significant, suggesting a recent change in climate patterns. The strength of the current time-lagged relationship suggests that it might have relevance for other temperature dependent ecological relationships. PMID- 27182712 TI - Chronic Foot Pain due to Pachyonychia Congenita in a Pediatric Patient: A Successful Management Strategy. AB - We report the case of an 11-year-old girl who presented to our multidisciplinary pain center with the chief complaint of chronic bilateral foot pain because of a rare congenital keratin disorder. This patient had been diagnosed with pachyonychia congenita, an extremely rare genetic disorder primarily affecting the skin and nails. The child had bilateral foot pain for years because of the characteristic blisters and calluses on the soles of her feet. Chronic pain was negatively impacting her quality of life; she was severely limited in her activities of daily living secondary to pain. Furthermore, she reported absenteeism from school, lack of social activities, and frequent nighttime awakenings. We discuss the successful management of her chronic foot pain using a multimodal, multidisciplinary approach. PMID- 27182713 TI - Nanoparticles Encapsulated with LL37 and Serpin A1 Promotes Wound Healing and Synergistically Enhances Antibacterial Activity. AB - Wound care is a serious healthcare concern, often complicated by prolonged inflammation and bacterial infection, which contributes significantly to mortality and morbidity. Agents commonly used to treat chronic wound infections are limited due to toxicity of the therapy, multifactorial etiology of chronic wounds, deep skin infections, lack of sustained controlled delivery of drugs, and development of drug resistance. LL37 is an endogenous host defense peptide possessing antimicrobial activity and is involved in the modulation of wound healing. Serpin A1 (A1) is an elastase inhibitor and has been shown to demonstrate wound-healing properties. Hence, our goal was to develop a topical combination nanomedicine for the controlled sustained delivery of LL37 and A1 at precise synergistic ratio combinations that will significantly promote wound closure, reduce bacterial contamination, and enhance anti-inflammatory activity. We have successfully developed the first solid lipid nanoparticle (SLN) formulation that can simultaneously deliver LL37 and A1 at specific ratios resulting in accelerated wound healing by promoting wound closure in BJ fibroblast cells and keratinocytes as well as synergistically enhancing antibacterial activity against S. aureus and E. coli in comparison to LL37 or A1 alone. PMID- 27182714 TI - Highly Reversible Zinc-Ion Intercalation into Chevrel Phase Mo6S8 Nanocubes and Applications for Advanced Zinc-Ion Batteries. AB - This work describes the synthesis of Chevrel phase Mo6S8 nanocubes and its application as the anode material for rechargeable Zn-ion batteries. Mo6S8 can host Zn(2+) ions reversibly in both aqueous and nonaqueous electrolytes with specific capacities around 90 mAh/g, and exhibited remarkable intercalation kinetics and cyclic stability. In addition, we assembled full cells by integrating Mo6S8 anodes with zinc-polyiodide (I(-)/I3(-))-based catholytes, and demonstrated that such full cells were also able to deliver outstanding rate performance and cyclic stability. This first demonstration of a zinc intercalating anode could inspire the design of advanced Zn-ion batteries. PMID- 27182715 TI - Reporter Immobilization Assay (REIA) for Bioconjugating Reactions. AB - Enzymes able to ligate biomolecules are emerging tools to generate site-specific bioconjugates. In this study we present a detection and screening method for bioconjugating enzymes which overcomes limitations of analytical methods such as HPLC or MS. These techniques are experimentally demanding and often limited in sensitivity and throughput compared to enzymatic assays. The principle of this Reporter Immobilization Assay (REIA) is the ligation of a reporter enzyme to a peptide carrying an affinity handle, which can be utilized for its isolation. The REIA system exhibits a high sensitivity with a linear range down to 1 MUg/mL (55 nM), a variation coefficient of 6.5%, and can be performed cost-efficiently in 96 well microtiter plate format. The application of this assay allowed the characterization of a thiol transpeptidase sortase from S. aureus which is an important drug target and a biotechnological tool for ligation and modification of proteins. Thereby, yet-undetectable promiscuous activity of sortase could be detected, e.g., the acceptance of alanine as nucleophile. In addition, we were able to provide evidence that the REIA is suitable for high throughput screening of enzyme libraries using crude cellular extract with a throughput of 600 samples per hour. PMID- 27182716 TI - A Shock-Tube Study of the CO + OH Reaction Near the Low-Pressure Limit. AB - Rate coefficients for the reaction between carbon monoxide and hydroxyl radical were measured behind reflected shock waves over 700-1230 K and 1.2-9.8 bar. The temperature/pressure conditions correspond to the predicted low-pressure limit of this reaction, where the channel leading to carbon dioxide formation is dominant. The reaction rate coefficients were inferred by measuring the formation of carbon dioxide using quantum cascade laser absorption near 4.2 MUm. Experiments were performed under pseudo-first-order conditions with tert-butyl hydroperoxide (TBHP) as the OH precursor. Using ultraviolet laser absorption by OH radicals, the TBHP decomposition rate was measured to quantify potential facility effects under extremely dilute conditions used here. The measured CO + OH rate coefficients are provided in Arrhenius form for three different pressure ranges: kCO+OH(1.2-1.6 bar) = (9.14 +/- 2.17) * 10(-13) exp(-(1265 +/- 190)/T) cm(3) molecule(-1) s(-1); kCO+OH(4.3-5.1 bar) = (8.70 +/- 0.84) * 10(-13) exp(-(1156 +/ 83)/T) cm(3) molecule(-1) s(-1); and kCO+OH(9.6-9.8 bar) = (7.48 +/- 1.92) * 10( 13) exp(-(929 +/- 192)/T) cm(3) molecule(-1) s(-1). The measured rate coefficients are found to be lower than the master equation modeling results by Weston et al. [J. Phys. Chem. A, 2013, 117, 821] at 819 K and in closer agreement with the expression provided by Joshi and Wang [Int. J. Chem. Kinet., 2006, 38, 57]. PMID- 27182717 TI - Cross-Coupling of Acrylamides and Maleimides under Rhodium Catalysis: Controlled Olefin Migration. AB - The rhodium(III)-catalyzed direct cross-coupling reaction of electron-deficient acrylamides with maleimides is described. This protocol displays broad functional group tolerance and high efficiency, which offers a new opportunity to access highly substituted succinimides. Dependent on the substituent positions of acrylamides and reaction conditions, olefin migrated products were obtained with high regio- and stereoselectivity. PMID- 27182718 TI - Resting Heart Rate Variability, Inflammation, and Insulin Resistance in Overweight and Obese Adolescents. AB - BACKGROUND: The prevalence of obesity is increasing in young people in the United States. Lately, low-grade inflammation is recognized as accompanying obesity, a known risk factor for type 2 diabetes. Autonomic dysfunction is a prominent feature of adult diabetes, but its prevalence in adolescents in prediabetic states or with diabetes risk factors is unknown. We undertook to study obesity, inflammation, insulin resistance, and autonomic dysfunction together in a population of adolescents aged 13-18 years. METHODS: Subjects gave a blood sample for cytokine analysis and a 5-min resting EKG for analysis of resting heart rate variability. TNF-alpha, IL-6, c-reactive protein (CRP), MCP-1, and IL-10 were analyzed by enzyme-linked immunosorbent assay, and Fourier Transform was applied to electrocardiographic recordings of R-R intervals for analysis in frequency space. The HOMA calculation was used as an index of insulin sensitivity. RESULTS: TNF-alpha, IL-6, CRP, MCP-1, HOMA, and insulin levels, but not serum glucose or IL-10, were higher in the obese subjects. Low-frequency (0.04-0.15 Hz) and high frequency (0.15-0.4 Hz) fluctuations of R-R intervals were lower in the obese subjects, but the normalized low-frequency power was not different, suggesting proportional reduction in variability in both ranges and impairment of both sympathetic and parasympathetic systems. CONCLUSIONS: Chronic low-grade inflammation, insulin resistance, and autonomic dysfunction are present at an early age in obese youths; early detection of inflammation may facilitate meaningful lifestyle changes in this high-risk group. PMID- 27182726 TI - Participation in School Food and Nutrition Activities among Grade 6-8 Students in Vancouver. AB - This study examined student-reported participation in school food and nutrition activities in Vancouver, British Columbia (BC), and whether engagement differed by gender and between elementary and secondary school students. A cross-sectional survey of grade 6-8 public school students (n = 937) from 20 elementary and 6 secondary schools assessed student-reported participation in a range of food and nutrition activities. Statistical analyses included descriptive statistics and multilevel logistic regression to examine associations between participation with gender and school type. Overall, <50% of students reported engaging in most of the food and nutrition activities examined in the 2011-2012 school year, including: food preparation (36%), choosing/tasting healthy foods (27%), learning about Canada's Food Guide (CFG) (45%), learning about foods grown in BC (35%), gardening (21%), composting (32%), and recycling (51%). Females were more likely to report recycling and learning about CFG and BC-grown foods (P < 0.05). Secondary students were more likely to report activities focused on working with or learning about food/nutrition (P < 0.05). Despite local and provincial efforts to engage students in food and nutrition experiences, participation in most activities remains relatively low, with few students exposed to multiple activities. Continued advocacy is needed from the dietetics community to improve student engagement in food and nutrition activities. PMID- 27182727 TI - Exotic Plant Infestation Is Associated with Decreased Modularity and Increased Numbers of Connectors in Mixed-Grass Prairie Pollination Networks. AB - The majority of pollinating insects are generalists whose lifetimes overlap flowering periods of many potentially suitable plant species. Such generality is instrumental in allowing exotic plant species to invade pollination networks. The particulars of how existing networks change in response to an invasive plant over the course of its phenology are not well characterized, but may shed light on the probability of long-term effects on plant-pollinator interactions and the stability of network structure. Here we describe changes in network topology and modular structure of infested and non-infested networks during the flowering season of the generalist non-native flowering plant, Cirsium arvense in mixed grass prairie at Badlands National Park, South Dakota, USA. Objectives were to compare network-level effects of infestation as they propagate over the season in infested and non-infested (with respect to C. arvense) networks. We characterized plant-pollinator networks on 5 non-infested and 7 infested 1-ha plots during 4 sample periods that collectively covered the length of C. arvense flowering period. Two other abundantly-flowering invasive plants were present during this time: Melilotus officinalis had highly variable floral abundance in both C. arvense-infested and non-infested plots and Convolvulus arvensis, which occurred almost exclusively in infested plots and peaked early in the season. Modularity, including roles of individual species, and network topology were assessed for each sample period as well as in pooled infested and non-infested networks. Differences in modularity and network metrics between infested and non-infested networks were limited to the third and fourth sample periods, during flower senescence of C. arvense and the other invasive species; generality of pollinators rose concurrently, suggesting rewiring of the network and a lag effect of earlier floral abundance. Modularity was lower and number of connectors higher in infested networks, whether they were assessed in individual sample periods or pooled into infested and non-infested networks over the entire blooming period of C. arvense. Connectors typically did not reside within the same modules as C. arvense, suggesting that effects of the other invasive plants may also influence the modularity results, and that effects of infestation extend to co-flowering native plants. We conclude that the presence of abundantly flowering invasive species is associated with greater network stability due to decreased modularity, but whether this is advantageous for the associated native plant-pollinator communities depends on the nature of perturbations they experience. PMID- 27182728 TI - Risk of premature cerebrovascular disease in patients with ankylosing spondylitis. AB - OBJECTIVES: Patients with ankylosing spondylitis (AS) are at an elevated risk for the development of coronary artery disease, but the risk cerebrovascular disease among these patients remains incompletely understood. We investigated the cerebrovascular risk profiles of patients with a cerebrovascular disease and AS and compared these profiles to those of cerebrovascular disease patients without AS. METHODS: We retrospectively analyzed 34 patients with ischemic cerebrovascular disease also diagnosed with AS and 597 controls without AS with respect to patient age, gender, cerebrovascular risk factors, and laboratory test results. RESULTS: AS patients were significantly younger than control patients in this study (56.2+/-13.5 years vs. 63.0+/-13.4 years, respectively; p=0.004). Logistic regression analysis did not indicate significant relationships between gender, cerebrovascular risk factors, and biochemical risk factors in AS patients, nor were any significant relationships found between erythrocyte sedimentation rate or C-reactive protein and biochemical risk factors. A low frequency of large-artery atherosclerosis and high frequency of small-vessel occlusion according to TOAST classification were found in AS patients with stroke. CONCLUSIONS: Among the patients included in this study, patients with AS sought treatment for cerebrovascular disease were at a younger age compared to control patients without AS. Thus, our results indicate that AS patients have an increased risk for the premature onset of cerebrovascular disease. And the premature atherosclerosis may associate with the patients with AS. Furthermore, the high frequency of the small-vessel stroke subtype in AS patients indicates that small-vessel inflammation may be involved in the pathogenesis of vascular diseases in AS patients. Further prospective study with more samples will be needed to confirm this point of view. PMID- 27182729 TI - Low-energy excited states of divanadium: a matrix isolation and MRCI study. AB - The ground and excited electronic states of the vanadium dimer (V2) have been studied using Ne matrix isolation experiments and quantum chemical calculations (multireference configuration interaction based on complete active space self consistent orbitals). In the near infrared absorption spectrum, two vibrational progressions of a new electronic term with a large number of members have been observed with the origin at 1.08 eV and a fundamental vibrational quantum of 475 cm(-1). With the aid of calculations, it has been assigned to a (3)Piu electronic term. The calculations yield potential energy curves for a large number of singlet, triplet, and quintet electronic terms. PMID- 27182730 TI - Predictive Value of C-Reactive Protein (CRP) in Identifying Fatal Outcome and Deep Infections in Staphylococcus aureus Bacteremia. AB - INTRODUCTION: Clear cut-off levels could aid clinicians in identifying patients with a risk of fatal outcomes or complications such as deep infection foci in Staphylococcus aureus bacteremia (SAB). Cut-off levels for widely used clinical follow-up parameters including serum C-reactive protein (CRP) levels and white blood cell counts (WBC) have not been previously studied. METHODS: 430 adult SAB patients in Finland took part in prospective multicentre study in which their CRP levels and WBC counts were measured on the day of the positive blood culture, every other day during the first week, twice a week during hospitalization and at 30 days. Receiver operating characteristic (ROC) analysis was used to evaluate the prognostic value of CRP and WBC on the day of the positive blood culture and at days 4, 7, and 14 in predicting mortality and the presence of deep infections at 30 days. Adjusted hazard ratios (HR) for CRP level and WBC count cut-off values for mortality were calculated by the Cox regression analysis and adjusted odds ratios (OR) for cut-off values to predict the presence of deep infection by the binary logistic regression analysis. RESULTS: The succumbing patients could be distinguished from the survivors, starting on day 4 after the positive blood culture, by higher CRP levels. Cut-off values of CRP for day 30 mortality in adjusted analysis, that significantly predicted fatal outcome were at day 4 CRP >103 mg/L with sensitivity of 77%, specificity of 55%, and HR of 3.5 (95% CI, 1.2 10.3; p = 0.024), at day 14 CRP >61 mg/L with a sensitivity of 82%, specificity of 80% and HR of 3.6 (95% CI, 1.1-10.3; p<0.039) and cut-off value of WBC at day 14 >8.6 x109/L was prognostic with sensitivity of 77%, specificity of 78% and HR of 8.2 (95% CI, 2.9-23.1; p<0.0001). Cut-off values for deep infection in adjusted analysis were on the day of the positive blood culture CRP >108 mg/L with sensitivity of 77%, specificity of 60%, and HR of 2.6 (95% CI, 1.3-4.9; p = 0.005) and at day 14 CRP >22 mg/L with sensitivity of 59%, specificity of 68%, and HR of 3.9 (95% CI, 1.6-9.5; p = 0.003). The lack of decline of CRP in 14 days or during the second week were neither prognostic nor markers of deep infection focus. CONCLUSIONS: CRP levels have potential for the early identification of SAB patients with a greater risk for death and deep infections. PMID- 27182731 TI - Success Factors of European Syndromic Surveillance Systems: A Worked Example of Applying Qualitative Comparative Analysis. AB - INTRODUCTION: Syndromic surveillance aims at augmenting traditional public health surveillance with timely information. To gain a head start, it mainly analyses existing data such as from web searches or patient records. Despite the setup of many syndromic surveillance systems, there is still much doubt about the benefit of the approach. There are diverse interactions between performance indicators such as timeliness and various system characteristics. This makes the performance assessment of syndromic surveillance systems a complex endeavour. We assessed if the comparison of several syndromic surveillance systems through Qualitative Comparative Analysis helps to evaluate performance and identify key success factors. MATERIALS AND METHODS: We compiled case-based, mixed data on performance and characteristics of 19 syndromic surveillance systems in Europe from scientific and grey literature and from site visits. We identified success factors by applying crisp-set Qualitative Comparative Analysis. We focused on two main areas of syndromic surveillance application: seasonal influenza surveillance and situational awareness during different types of potentially health threatening events. RESULTS: We found that syndromic surveillance systems might detect the onset or peak of seasonal influenza earlier if they analyse non clinical data sources. Timely situational awareness during different types of events is supported by an automated syndromic surveillance system capable of analysing multiple syndromes. To our surprise, the analysis of multiple data sources was no key success factor for situational awareness. CONCLUSIONS: We suggest to consider these key success factors when designing or further developing syndromic surveillance systems. Qualitative Comparative Analysis helped interpreting complex, mixed data on small-N cases and resulted in concrete and practically relevant findings. PMID- 27182732 TI - The Effectiveness of Mindfulness-Based Interventions in the Perinatal Period: A Systematic Review and Meta-Analysis. AB - Perinatal mental health difficulties are associated with adverse consequences for parents and infants. However, the potential risks associated with the use of psychotropic medication for pregnant and breastfeeding women and the preferences expressed by women for non-pharmacological interventions mean it is important to ensure that effective psychological interventions are available. It has been argued that mindfulness-based interventions may offer a novel approach to treating perinatal mental health difficulties, but relatively little is known about their effectiveness with perinatal populations. This paper therefore presents a systematic review and meta-analysis of the effectiveness of mindfulness-based interventions for reducing depression, anxiety and stress and improving mindfulness skills in the perinatal period. A systematic review identified seventeen studies of mindfulness-based interventions in the perinatal period, including both controlled trials (n = 9) and pre-post uncontrolled studies (n = 8). Eight of these studies also included qualitative data. Hedge's g was used to assess uncontrolled and controlled effect sizes in separate meta analyses, and a narrative synthesis of qualitative data was produced. Pre- to post-analyses showed significant reductions in depression, anxiety and stress and significant increases in mindfulness skills post intervention, each with small to medium effect sizes. Completion of the mindfulness-based interventions was reasonable with around three quarters of participants meeting study-defined criteria for engagement or completion where this was recorded. Qualitative data suggested that participants viewed mindfulness interventions positively. However, between-group analyses failed to find any significant post-intervention benefits for depression, anxiety or stress of mindfulness-based interventions in comparison to control conditions: effect sizes were negligible and it was conspicuous that intervention group participants did not appear to improve significantly more than controls in their mindfulness skills. The interventions offered often deviated from traditional mindfulness-based cognitive therapy or mindfulness-based stress reduction programmes, and there was also a tendency for studies to focus on healthy rather than clinical populations, and on antenatal rather than postnatal populations. It is argued that these and other limitations with the included studies and their interventions may have been partly responsible for the lack of significant between-group effects. The implications of the findings and recommendations for future research are discussed. PMID- 27182735 TI - Sequential Measurement of Intermodal Variability in Public Transportation PM2.5 and CO Exposure Concentrations. AB - A sequential measurement method is demonstrated for quantifying the variability in exposure concentration during public transportation. This method was applied in Hong Kong by measuring PM2.5 and CO concentrations along a route connecting 13 transportation-related microenvironments within 3-4 h. The study design takes into account ventilation, proximity to local sources, area-wide air quality, and meteorological conditions. Portable instruments were compacted into a backpack to facilitate measurement under crowded transportation conditions and to quantify personal exposure by sampling at nose level. The route included stops next to three roadside monitors to enable comparison of fixed site and exposure concentrations. PM2.5 exposure concentrations were correlated with the roadside monitors, despite differences in averaging time, detection method, and sampling location. Although highly correlated in temporal trend, PM2.5 concentrations varied significantly among microenvironments, with mean concentration ratios versus roadside monitor ranging from 0.5 for MTR train to 1.3 for bus terminal. Measured inter-run variability provides insight regarding the sample size needed to discriminate between microenvironments with increased statistical significance. The study results illustrate the utility of sequential measurement of microenvironments and policy-relevant insights for exposure mitigation and management. PMID- 27182733 TI - Lipidomic Profiling of Adipose Tissue Reveals an Inflammatory Signature in Cancer Related and Primary Lymphedema. AB - Cancer-related and primary lymphedema (LE) are associated with the production of adipose tissue (AT). Nothing is known, however, about the lipid-based molecules that comprise LE AT. We therefore analyzed lipid molecules in lipoaspirates and serum obtained from LE patients, and compared them to lipoaspirates from cosmetic surgery patients and healthy control cohort serum. LE patient serum analysis demonstrated that triglycerides, HDL- and LDL-cholesterol and lipid transport molecules remained within the normal range, with no alterations in individual fatty acids. The lipidomic analysis also identified 275 lipid-based molecules, including triacylglycerides, diacylglycerides, fatty acids and phospholipids in AT oil and fat. Although the majority of lipid molecules were present in a similar abundance in LE and non-LE samples, there were several small changes: increased C20:5-containing triacylglycerides, reduced C10:0 caprinic and C24:1 nervonic acids. LE AT oil also contained a signature of increased cyclopropane type fatty acids and inflammatory mediators arachidonic acid and ceramides. Interestingly C20:5 and C22:6 omega-3-type lipids are increased in LE AT, correlating with LE years. Hence, LE AT has a normal lipid profile containing a signature of inflammation and omega-3-lipids. It remains unclear, however, whether these differences reflect a small-scale global metabolic disturbance or effects within localised inflammatory foci. PMID- 27182734 TI - Genetic Variability of West Nile Virus in U.S. Blood Donors from the 2012 Epidemic Season. AB - West Nile virus (WNV) is an arbovirus maintained in nature in a bird-mosquito enzootic cycle which can also infect other vertebrates including humans. WNV is now endemic in the United States (U.S.), causing yearly outbreaks that have resulted in an estimated total of 4-5 million human infections. Over 41,700 cases of West Nile disease, including 18,810 neuroinvasive cases and 1,765 deaths, were reported to the CDC between 1999 and 2014. In 2012, the second largest West Nile outbreak in the U.S. was reported, which caused 5,674 cases and 286 deaths. WNV continues to evolve, and three major WNV lineage I genotypes (NY99, WN02, and SW/WN03) have been described in the U.S. since introduction of the virus in 1999. We report here the WNV sequences obtained from 19 human samples acquired during the 2012 U.S. outbreak and our examination of the evolutionary dynamics in WNV isolates sequenced from 1999-2012. Maximum-likelihood and Bayesian methods were used to perform the phylogenetic analyses. Selection pressure analyses were performed with the HyPhy package using the Datamonkey web-server. Using different codon-based and branch-site selection models, we detected a number of codons subjected to positive pressure in WNV genes. Thirteen of the 19 completely sequenced isolates from 10 U.S. states were genetically similar, sharing up to 55 nucleotide mutations and 4 amino acid substitutions when compared with the prototype isolate WN-NY99. Overall, these analyses showed that following a brief contraction in 2008-2009, WNV genetic divergence in the U.S. continued to increase in 2012, and that closely related variants were found across a broad geographic range of the U.S., coincident with the second-largest WNV outbreak in U.S. PMID- 27182737 TI - N-Alpha-Acetyltransferases and Regulation of CFTR Expression. AB - The majority of cystic fibrosis (CF)-causing mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) lead to the misfolding, mistrafficking, and degradation of the mutant protein. Inhibition of degradation does not effectively increase the amount of trafficking competent CFTR, but typically leads to increased ER retention of misfolded forms. Thus, the initial off pathway steps occur early in the processing of the protein. To identify proteins that interact with these early forms of CFTR, in vitro crosslink experiments identified cotranslational partners of the nascent chain of the severe misfolded mutant, G85E CFTR. The mutant preferentially interacts with a subunit of an N-alpha-acetyltransferase A. Based on recent reports that acetylation of the N-termini of some N-end rule substrates control their ubiquitination and subsequent degradation, a potential role for this modification in regulation of CFTR expression was assessed. Knockdown experiments identified two complexes, which affect G85E CFTR proteins levels, NatA and NatB. Effects of the knockdowns on mRNA levels, translation rates, and degradation rates established that the two complexes regulate G85E CFTR through two separate mechanisms. NatA acts indirectly by regulating transcription levels and NatB acts through a previously identified, but incompletely understood posttranslational mechanism. This regulation did not effect trafficking of G85E CFTR, which remains retained in the ER, nor did it alter the degradation rate of CFTR. A mutation predicted to inhibit N-terminal acetylation of CFTR, Q2P, was without effect, suggesting neither system acts directly on CFTR. These results contradict the prediction that N-terminal acetylation of CFTR determines its fitness as a proteasome substrate, but rather NatB plays a role in the conformational maturation of CFTR in the ER through actions on an unidentified protein. PMID- 27182736 TI - Universal Coverage without Universal Access: Institutional Barriers to Health Care among Women Sex Workers in Vancouver, Canada. AB - BACKGROUND: Access to health care is a crucial determinant of health. Yet, even within settings that purport to provide universal health coverage (UHC), sex workers' experiences reveal systematic, institutionally ingrained barriers to appropriate quality health care. The aim of this study was to assess prevalence and correlates of institutional barriers to care among sex workers in a setting with UHC. METHODS: Data was drawn from an ongoing community-based, prospective cohort of women sex workers in Vancouver, Canada (An Evaluation of Sex Workers' Health Access). Multivariable logistic regression analyses, using generalized estimating equations (GEE), were employed to longitudinally investigate correlates of institutional barriers to care over a 44-month follow-up period (January 2010-August 2013). RESULTS: In total, 723 sex workers were included, contributing to 2506 observations. Over the study period, 509 (70.4%) women reported one or more institutional barriers to care. The most commonly reported institutional barriers to care were long wait times (54.6%), limited hours of operation (36.5%), and perceived disrespect by health care providers (26.1%). In multivariable GEE analyses, recent partner- (adjusted odds ratio [AOR] = 1.46, % 95% Confidence Interval [CI] 1.10-1.94), workplace- (AOR = 1.31, 95% CI 1.05 1.63), and community-level violence (AOR = 1.41, 95% CI 1.04-1.92), as well as other markers of vulnerability, such as self-identification as a gender/sexual minority (AOR = 1.32, 95% CI 1.03-1.69), a mental illness diagnosis (AOR = 1.66, 95% CI 1.34-2.06), and lack of provincial health insurance card (AOR = 3.47, 95% CI 1.59-7.57) emerged as independent correlates of institutional barriers to health services. DISCUSSION: Despite Canada's UHC, women sex workers in Vancouver face high prevalence of institutional barriers to care, with highest burden among most marginalized women. These findings underscore the need to explore new models of care, alongside broader policy changes to fulfill sex workers' health and human rights. PMID- 27182738 TI - Enantioselective Formal Synthesis of Nectrisine Using a Palladium-Catalyzed Asymmetric Allylic Amination and Cross-Metathesis as Key Steps. AB - A formal enantioselective synthesis of nectrisine, a potent alpha-glucosidase inhibitor, was carried out starting from butadiene monoepoxide through a synthetic sequence involving enantioselective allylic substitution, cross metathesis, dihydroxylation, and cyclization. PMID- 27182741 TI - A gold nanocluster-based fluorescent probe for simultaneous pH and temperature sensing and its application to cellular imaging and logic gates. AB - Metal nanocluster-based nanomaterials for the simultaneous determination of temperature and pH variations in micro-environments are still a challenge. In this study, we develop a dual-emission fluorescent probe consisting of bovine serum albumin-stabilized gold nanoclusters (BSA-AuNCs) and fluorescein-5 isothiocyanate (FITC) as temperature- and pH-responsive fluorescence signals. Under single wavelength excitation the FITC/BSA-AuNCs exhibited well-separated dual emission bands at 525 and 670 nm. When FITC was used as a reference fluorophore, FITC/BSA-AuNCs showed a good linear response over the temperature range 1-71 degrees C and offered temperature-independent spectral shifts, temperature accuracy, activation energy, and reusability. The possible mechanism for high temperature-induced fluorescence quenching of FITC/BSA-AuNCs could be attributed to a weakening of the Au-S bond, thereby lowering the charge transfer from BSA to AuNCs. Additionally, the pH- and temperature-responsive properties of FITC/BSA-AuNCs allow simultaneous temperature sensing from 21 to 41 degrees C (at intervals of 5 degrees C) and pH from 6.0 to 8.0 (at intervals of 0.5 pH unit), facilitating the construction of two-input AND logic gates. Three-input AND logic gates were also designed using temperature, pH, and trypsin as inputs. The practicality of using FITC/BSA-AuNCs to determine the temperature and pH changes in HeLa cells is also validated. PMID- 27182739 TI - Axl Expression Stratifies Patients with Poor Prognosis after Hepatectomy for Hepatocellular Carcinoma. AB - BACKGROUND: Axl is a receptor tyrosine kinase which plays an important role in multiple human malignancies. DESIGN: The Axl expression was examined in several hepatocellular carcinoma(HCC) cell lines, paired tumor and nontumorous samples. Then, we examined cell growth curve, cell apoptosis and cell migration in SMMC 7721 cells over-expressed with Axl or siRNA against Axl, respectively. Finally, the prognostic value of Axl was investigated in a prospective cohort of 246 consecutive HCC patients undergoing curative hepatoectomy. RESULTS: We found Axl was positive in 22% of examined tumor tissues and all four cell lines. Over expressing Axl in SMMC-7721 cells accelerated cell growth, cell migration and inhibited cell apoptosis, while knock-down of Axl exerted opposite effect. Axl expression was closely associated with serum AFP, multiple tumors, absence of encapsulation, microvascular invasion, and advanced BCLC or TNM stage. Patients with positive Axl staining had a higher 5-year recurrence rate (92% vs. 71%, P<0.001) and a lower 5-year survival rate (9% vs. 48%, P<0.001) than those with negative staining. The multivariate analyses showed that Axl expression was an independent factor for both tumor recurrence (HR: 1.725; 95% CI: 1.219-2.441) and survival (1.847; 1.291-2.642). CONCLUSION: Axl expression suggests more aggressive tumor invasiveness and predicts worse prognosis for HCC patients undergoing resection. PMID- 27182742 TI - Research to Improve Urological Health for Women and Girls: Focus on Prevention. PMID- 27182740 TI - Novel Lesions of Bones and Joints Associated with Chikungunya Virus Infection in Two Mouse Models of Disease: New Insights into Disease Pathogenesis. AB - Chikungunya virus is an arbovirus spread predominantly by Aedes aegypti and Ae. albopictus mosquitoes, and causes debilitating arthralgia and arthritis. While these are common manifestations during acute infection and it has been suggested they can recur in patients chronically, gaps in knowledge regarding the pathogenesis still exist. Two established mouse models were utilized (adult IRF 3/7 -/- -/- and wild-type C57BL/6J mice) to evaluate disease manifestations in bones and joints at various timepoints. Novel lesions in C57BL/6J mice consisted of periostitis (91%) and foci of cartilage of necrosis (50% of mice at 21 DPI). Additionally, at 21 DPI, 50% and 75% of mice exhibited periosteal bone proliferation affecting the metatarsal bones, apparent via histology and MUCT, respectively. MUCT analysis did not reveal any alterations in trabecular bone volume measurements in C57BL/6J mice. Novel lesions demonstrated in IRF 3/7 -/- /- mice at 5 DPI included focal regions of cartilage necrosis (20%), periosteal necrosis (66%), and multifocal ischemic bone marrow necrosis (100%). Contralateral feet in 100% of mice of both strains had similar, though milder lesions. Additionally, comparison of control IRF 3/7 -/- -/- and wild-type C57BL/6J mice demonstrated differences in cortical bone. These experiments demonstrate novel manifestations of disease similar to those occurring in humans, adding insight into disease pathogenesis, and representing new potential targets for therapeutic interventions. Additionally, results demonstrate the utility of MUCT in studies of bone and joint pathology and illustrate differences in bone dynamics between mouse strains. PMID- 27182744 TI - Rational Design of Methodology-Independent Metal Parameters Using a Nonbonded Dummy Model. AB - A nonbonded dummy model for metal ions is highly imperative for the computation of complex biological systems with for instance multiple metal centers. Here we present nonbonded dummy parameters of 11 divalent metallic cations, namely, Mg(2+), V(2+), Cr(2+), Mn(2+), Fe(2+), Co(2+), Ni(2+), Zn(2+), Cd(2+), Sn(2+), and Hg(2+), that are optimized to be compatible with three widely used water models (TIP3P, SPC/E, and TIP4P-EW). The three sets of metal parameters reproduce simultaneously the solvation free energies (DeltaGsol), the ion-oxygen distance in the first solvation shell (IOD), and coordination numbers (CN) in explicit water with a relative error less than 1%. The main sources of errors to DeltaGsol that arise from the boundary conditions and treatment of electrostatic interactions are corrected rationally, which ensures the independence of the proposed parameters on the methodology used in the calculation. This work will be of great value for the computational study of metal-containing biological systems. PMID- 27182745 TI - Erratum: PGC-1alpha controls mitochondrial biogenesis and dynamics in lead induced neurotoxicity. PMID- 27182743 TI - Induced Pluripotent Stem Cell-Derived Retinal Pigmented Epithelium: A Comparative Study Between Cell Lines and Differentiation Methods. AB - PURPOSE: The application of induced pluripotent stem cell-derived retinal pigmented epithelium (iPSC-RPE) in patients with retinal degenerative disease is making headway toward the clinic, with clinical trials already underway. Multiple groups have developed methods for RPE differentiation from pluripotent cells, but previous studies have shown variability in iPSC propensity to differentiate into RPE. METHODS: This study provides a comparison between 2 different methods for RPE differentiation: (1) a commonly used spontaneous continuously adherent culture (SCAC) protocol and (2) a more rapid, directed differentiation using growth factors. Integration-free iPSC lines were differentiated to RPE, which were characterized with respect to global gene expression, expression of RPE markers, and cellular function. RESULTS: We found that all 5 iPSC lines (iPSC-1, iPSC-2, iPSC-3, iPSC-4, and iPSC-12) generated RPE using the directed differentiation protocol; however, 2 of the 5 iPSC lines (iPSC-4 and iPSC-12) did not yield RPE using the SCAC method. Both methods can yield bona fide RPE that expresses signature RPE genes and carry out RPE functions, and are similar, but not identical to fetal RPE. No differences between methods were detected in transcript levels, protein localization, or functional analyses between iPSC-1 RPE, iPSC-2-RPE, and iPSC-3-RPE. Directed iPSC-3-RPE showed enhanced transcript levels of RPE65 compared to directed iPSC-2-RPE and increased BEST1 expression and pigment epithelium-derived factor (PEDF) secretion compared to directed iPSC 1-RPE. In addition, SCAC iPSC-3-RPE secreted more PEDF than SCAC iPSC-1-RPE. CONCLUSIONS: The directed protocol is a more reliable method for differentiating RPE from various pluripotent sources and some iPSC lines are more amenable to RPE differentiation. PMID- 27182747 TI - Comparative Clinical Outcomes of Pediatric Patients Presenting With Eyelid Nodules of Idiopathic Facial Aseptic Granuloma, Hordeola, and Chalazia. AB - PURPOSE: To present the clinical features of the eyelid nodules observed in a newly determined dermatologic disorder, idiopathic facial aseptic granuloma (IFAG), and to compare them with children having acute hordeolum and chalazion. METHODS: Duration of the lesion, localization, presence of coexisting facial nodules, management strategies, and response time to topical/oral antibiotics were retrospectively reviewed in 50 children with IFAG, acute hordeolum, or chalazion. RESULTS: Fourteen children with one or more IFAG nodules on their eyelids, 28 children with one or more acute hordeolum, and 8 children with one or more chalazion were examined. Children with IFAG on their eyelids and face presented earlier than children with acute hordeolum (P = .006). The duration of this lesion was similar among patients with IFAG on their eyelids and acute hordeolum (P = .53). Duration of the lesion and treatment response time were shorter in children with IFAG on their eyelids and face (P = .004) than in those with IFAG on their eyelids (P = .013). The lesions of patients with chalazion had a longer duration compared to those with IFAG on their eyelids (P = .005), IFAG on their eyelids and face (P < .001), and acute hordeolum (P = .04). Twenty patients with acute hordeolum recovered after topical antibiotics and had a similar treatment response time to those with IFAG on their eyelids and face (P = .06) and those with IFAG on their eyelids (P = .16). CONCLUSIONS: IFAG should be considered in the differential diagnosis of painless eyelid nodules in children. Because IFAG on the eyelids has many overlapping features with hordeola/chalazia, its differentiation may be difficult in the absence of accompanying facial granulomas. Chronic subepidermal eyelid nodules resembling skin abscess should alert clinicians for IFAG. Because IFAG responds well to oral clarithromycin, unnecessary surgical interventions should be avoided in these cases. [J Pediatr Ophthalmol Strabismus. 2016;53(4):206-211.]. PMID- 27182746 TI - Specialty Practice and Cost Considerations in the Management of Uveitis Associated With Juvenile Idiopathic Arthritis. AB - PURPOSE: To evaluate whether cost, prior insurance authorization concerns, and subspecialty practice influence therapeutic decisions in the treatment of uveitis associated with juvenile idiopathic arthritis. METHODS: A total of 2,965 pediatric ophthalmologists, uveitis specialists, retina specialists, and rheumatologists across the United States were surveyed via e-mail regarding their choice in long-term therapy for a hypothetical patient with uveitis associated with juvenile idiopathic arthritis. Outcomes of interest were differences in therapy choice based on cost/prior authorization and specialty practice. RESULTS: There were significant differences in the use of methotrexate and biologics among specialists, both with and without consideration for cost and prior authorization. CONCLUSIONS: Physicians in four different specialties who treat uveitis associated with juvenile idiopathic arthritis agree on methotrexate as a first-line treatment choice and a biologic immunosuppressive medication as a second choice, but there are significant differences between the specialties in their use of these medications. Cost and insurance considerations did not affect therapy selection. [J Pediatr Ophthalmol Strabismus. 2016;53(4):246-251.]. PMID- 27182749 TI - Comparison of Anterior Segment Parameters Obtained by Dual-Scheimpflug Analyzer Before and After Cycloplegia in Children. AB - PURPOSE: To assess the changes of anterior segment parameters with cycloplegia. METHODS: A cross-sectional study of healthy pediatric patients was performed. Anterior segment parameters were obtained by the Galilei Dual-Scheimpflug analyzer (Ziemer Group, Port, Switzerland) before and 40 minutes after the instillation of cyclopentolate. The effect of gender was evaluated. RESULTS: There were 43 boys and 50 girls with a mean age of 7.76 +/- 2.7 years. There was a significant increase in anterior chamber depth, anterior chamber volume, and pupil diameter after the cycloplegia (P < .05). The anterior chamber angle increased after cycloplegia in the nasal, temporal, and inferior quadrants (P < .05), but not in the superior quadrant (P > .05). The mean values of anterior segment parameters were similar in both genders. CONCLUSIONS: The values of anterior chamber depth, anterior chamber volume, anterior chamber angle, and pupil diameter measured with the Galilei Dual-Scheimpflug analyzer increased significantly after cycloplegia. Gender did not have an effect on anterior segment parameters. [J Pediatr Ophthalmol Strabismus. 2016;53(4):234-237.]. PMID- 27182748 TI - Ocular Findings in Children With 22q11.2 Deletion Syndrome. AB - PURPOSE: To identify the ocular features of children diagnosed as having 22q11.2 deletion syndrome in a Turkish population, which is the most common microdeletion syndrome with a wide range of facial and ocular abnormalities. METHODS: Sixteen children aged between 4 months and 18 years with a microdeletion in chromosome 22q11.2 underwent a detailed ophthalmological examination including uncorrected and best corrected visual acuity testing, stereoscopic vision examination, biomicroscopic and indirect fundus examination, and ocular motility testing. RESULTS: All patients had at least one ocular abnormality. The major abnormalities were eyelid abnormalities (eye hooding, narrow palpebral fissure, telecanthus, hypertelorism, sparse and thin eyebrows and eyelashes, blepharitis, and distichiasis), posterior embryotoxon, and tortuous retinal vessels in at least half of the patients. Other ophthalmological disorders were refractive errors, iris remnants, and strabismus. CONCLUSIONS: The chromosome 22q11.2 deletion syndrome is associated with a wide range of ocular disorders, which necessitates a comprehensive eye examination for appropriate treatment and follow up. Ocular findings sometimes can provide a clue to the diagnosis of 22q11.2 deletion. [J Pediatr Ophthalmol Strabismus. 2016;53(4):218-222]. PMID- 27182750 TI - Three-Dimensional Screen: A Comprehensive Approach to the Health Monitoring of Zebrafish. AB - Considering the numbers of zebrafish held in the laboratories, it is relevant to develop some tools to monitor the health of the animals, as well as their biotope. Environmental samples can be used to detect aquatic pathogens. Comprehensive health monitoring would thus seek pathogens in three dimensions of the animals and microbes' habitat: the fish, the sludge, and the water. This three-dimensional approach is called the 3D screen and it introduces some complementary tools to routine sentinel screening. For example, sludge and sump swabs analyses allow an efficient detection of pathogens at a low cost and with a fast turnover. These assays are particularly useful in cases of Pseudocapillaria tomentosa infestation or Mycobacterium haemophilum outbreak. Indeed, such a broader choice of diagnostic tests gives flexibility for the veterinarian to investigate Mycobacterium spp. presence in the water systems and fish colonies. Some other robust additional analysis, like the mortality rate monitoring, quickens the decision-making process. The 3D screen describes how this new toolbox can be used efficiently to monitor laboratory fish health. PMID- 27182751 TI - Negative Pressures and Spallation in Water Drops Subjected to Nanosecond Shock Waves. AB - Most experimental studies of cavitation in liquid water at negative pressures reported cavitation at tensions significantly smaller than those expected for homogeneous nucleation, suggesting that achievable tensions are limited by heterogeneous cavitation. We generated tension pulses with nanosecond rise times in water by reflecting cylindrical shock waves, produced by X-ray laser pulses, at the internal surface of drops of water. Depending on the X-ray pulse energy, a range of cavitation phenomena occurred, including the rupture and detachment, or spallation, of thin liquid layers at the surface of the drop. When spallation occurred, we evaluated that negative pressures below -100 MPa were reached in the drops. We model the negative pressures from shock reflection experiments using a nucleation-and-growth model that explains how rapid decompression could outrun heterogeneous cavitation in water, and enable the study of stretched water close to homogeneous cavitation pressures. PMID- 27182753 TI - Cozen's phenomenon revisited. AB - We retrospectively examined Cozen's fractures in children treated with a cast in extension with a varus mold applied as described by Rang. To our knowledge, no study has examined the effectiveness of this treatment. Our review included 14 patients with an average age of 3 years. The average time to valgus deformity was 8.8 months (range 5-15 months). Follow-up was 16.2 months (range 6.7-42.8 months). Seven (50%) patients developed a 5 degrees valgus deformity in addition to the normal valgus of the contralateral side. In conclusion, treatment with a long leg cast with the knee in extension and a varus mold minimized the valgus deformity compared with previous reports in the literature. PMID- 27182752 TI - Calcifying aponeurotic fibroma in children: our experience and a literature review. AB - Calcified aponeurotic fibroma is a rare benign fibrous tumour with characteristic histopathological features commonly observed in children and adolescents. It usually involves the most distal part of the extremities. Despite being a benign tumour, it has a high risk of local recurrence. We report our experience treating four children with calcifying aponeurotic fibroma who underwent surgical excision of the tumour. Two of them developed a local recurrence: one required a surgical revision, whereas the other currently continues to be under observation. The incidence found over a 5-year period (2010-2015) may lead us to consider that this condition is not as rare as reported and may often be misdiagnosed. PMID- 27182754 TI - Psychometric evaluation of the Scoliosis Research Society-22 Revised questionnaire among adolescents with idiopathic scoliosis. AB - This cross-sectional descriptive study was carried out to develop and evaluate the reliability and validity of the Korean version of the Scoliosis Research Society-22 Revised (SRS-22r) questionnaire among adolescents with idiopathic scoliosis. Of the initial 122 adolescents surveyed, 87 adolescents returned the second questionnaire, which assessed test-retest reliability between SRS-22r and the pediatric quality of life inventory questionnaire (PedsQL 4.0). The results were found to be reliable and valid, with acceptable internal consistency, intraclass correlation, and moderate correlation with a similar questionnaire. The SRS-22r can be used to assess health-related quality of life internationally among adolescents with scoliosis. PMID- 27182755 TI - Specific Single-Cell Isolation of Escherichia coli O157 from Environmental Water Samples by Using Flow Cytometry and Fluorescence-Activated Cell Sorting. AB - Contamination of food and water with pathogenic bacteria is of concern. Although culture-independent detection and quantification of pathogens is useful, isolation of pathogenic bacteria is still important when identifying the sources of pathogens. Here, we report the use of flow cytometry (FCM) and fluorescence activated cell sorting (FACS) to specifically detect and isolate individual Escherichia coli O157:H7 cells from water samples. When present at >10 cells/mL water, target pathogen was specifically detected and isolated. The FACS-sorted E. coli O157:H7 population reflected the original population diversity, in contrast to the populations obtained by immunomagnetic separation. Relative abundance of multiple pathogenic strains is important when performing source-tracking studies; therefore, single-cell isolation with FCM-FACS can be a useful tool to obtain pathogenic bacteria for source tracking purpose. PMID- 27182757 TI - Range prediction for tissue mixtures based on dual-energy CT. AB - The use of dual-energy CT (DECT) potentially decreases range uncertainties in proton and ion therapy treatment planning via determination of the involved physical target quantities. For eventual clinical application, the correct treatment of tissue mixtures and heterogeneities is an essential feature, as they naturally occur within a patient's CT. Here, we present how existing methods for DECT-based ion-range prediction can be modified in order to incorporate proper mixing behavior on several structural levels. Our approach is based on the factorization of the stopping-power ratio into the relative electron density and the relative stopping number. The latter is confined for tissue between about 0.95 and 1.02 at a therapeutic beam energy of 200 MeV u(-1) and depends on the I value. We show that convenient mixing and averaging properties arise by relating the relative stopping number to the relative cross section obtained by DECT. From this, a maximum uncertainty of the stopping-power ratio prediction below [Formula: see text] is suggested for arbitrary mixtures of human body tissues. PMID- 27182756 TI - The effect of different implant biomaterials on the behavior of canine bone marrow stromal cells during their differentiation into osteoblasts. AB - We investigated the effects of different implant biomaterials on cultured canine bone marrow stromal cells (BMSC) undergoing differentiation into osteoblasts (dBMSC). BMSC were isolated from canine humerus by marrow aspiration, cultured and differentiated on calcium phosphate scaffold (CPS), hydroxyapatite, hydroxyapatite in gel form and titanium mesh. We used the MTT method to determine the effects of osteogenic media on proliferation. The characteristics of dBMSC were assessed using alizarin red (AR), immunocytochemistry and osteoblastic markers including alkaline phosphatase/von Kossa (ALP/VK), osteocalcin (OC) and osteonectin (ON), and ELISA. The morphology of dBMSC on the biomaterials was investigated using inverted phase contrast microscopy and scanning electron microscopy. We detected expression of ALP/VK, AR, OC and ON by day 7 of culture; expression increased from day 14 until day 21. CPS supported the best adhesion, cell spreading, proliferation and differentiation of BMSCs. The effects of the biomaterials depended on their surface properties. Expression of osteoblastic markers showed that canine dBMSCs became functional osteoblasts. Tissue engineered stem cells can be useful clinically for autologous implants for treating bone wounds. PMID- 27182758 TI - Lower Experiential Avoidance Is Associated With Psychological Well-being and Improved Cardiopulmonary Endurance Among Patients in Cardiac Rehabilitation. AB - PURPOSE: Patients with a diagnosis of cardiac disease are often asked to make significant lifestyle changes, but they may experience difficulty initiating and maintaining lifestyle changes, especially when engaging in experiential avoidance (EA), the tendency to push away unpleasant emotions and sensations. This study examined the relationship between EA, psychological functioning, cardiac-quality of life (cardiac-QOL), program adherence, and cardiopulmonary endurance among patients entering an outpatient cardiac rehabilitation (CR) program. METHODS: Patients completed study questionnaires pre-CR, including 2 measures of EA (general and cardiac-specific), and assessments of psychological functioning and cardiac-QOL. Adherence was calculated as the proportion of insurance-approved CR sessions attended. Thirty participants completed stress testing pre-CR and post CR. RESULTS: Forty-seven patients completed the questionnaires. General EA was associated with greater depression (r = 0.73, P < .001), anxiety (r = 0.56, P < .001), and stress (r = 0.65, P < .001) and lower cardiac-QOL (r =-0.69, P < .001). In addition, when controlling for the influence of general EA, greater cardiac-specific EA was associated with depression ([INCREMENT]R = 0.05, P = .01), anxiety ([INCREMENT]R = 0.18, P < .001), and poorer cardiac-QOL ([INCREMENT]R = 0.04, P = .04). However, lower cardiac-specific EA predicted greater increases in cardiopulmonary endurance ((Equation is included in full text article.)O2peak) during the CR program (b =-0.18, P = .002; [INCREMENT]adjusted R = 0.07). Experiential avoidance was not associated with adherence. CONCLUSIONS: Lower EA is associated with better psychological well being among patients entering a CR program and with better exercise outcomes. Strategies for reducing EA may be important to consider in future clinical studies. PMID- 27182759 TI - Severity of Depressive Symptoms Pre- and Postcardiac Rehabilitation: A COMPARISON AMONG PATIENTS IN BRAZIL, CANADA, COLOMBIA, THE UNITED STATES, AND VENEZUELA. AB - PURPOSE: Depression is 3 times more prevalent in the cardiac than the general population in high-income countries and is particularly high in middle-income countries. Comorbid depression is associated with twice the mortality after a cardiovascular event. The objectives of this study were to describe and compare depressive symptoms pre- and postcardiac rehabilitation (CR) among patients in high-income countries and middle-income countries in the Americas. METHODS: The study design was prospective and observational. A convenience sample of CR participants completed the Patient Health Questionnaire-9 (PHQ-9) at CR intake and again at program discharge. Clinical data were extracted from medical charts. RESULTS: There were 779 participants: 45 Brazilian (5.8% of sample), 214 Canadian (27.5%), 126 Colombian (16.2%), 309 American (39.7%), and 85 Venezuelan (10.9%). Pre-CR depressive symptoms significantly differed between countries (P < .05), with Colombian participants reporting higher scores than Canadians and Venezuelans. Total PHQ-9 scores significantly decreased during CR in Colombia (mean change =-2.33; P < .001), the United States (mean change =-1.12; P < .001), and Venezuela (mean change =-2.14; P < .001), but not in Brazil (where less psychosocial intervention was offered) or Canada (where pre-CR scores were low). Among the 102 (13.1%) participants with scores in the elevated range pre-CR, the mean change in PHQ-9 scores was -6.57 +/- 1.09 and 40 (39.2%) participants no longer had elevated symptoms postprogram. CONCLUSIONS: Depressive symptoms are variable among patients with CR in South and North American countries. CR programs incorporating psychosocial components can reduce these symptoms. PMID- 27182760 TI - Utility of Screening for Obstructive Sleep Apnea in Cardiac Rehabilitation. AB - PURPOSE: Obstructive sleep apnea (OSA) is prevalent in patients with cardiovascular disease and is often undiagnosed. The purpose of this study was to determine the utility of communicating OSA risk with the patients in a diabetes and cardiac rehabilitation program (CRP) and primary care physicians. METHODS: Following an OSA education session, 295 patients in diabetes and CRPs were screened for OSA and daytime sleepiness by STOP-BANG and Epworth Sleepiness Scale questionnaires. Letters were sent to patients at high risk or noncompliant with continuous positive airway pressure (CPAP) treatment and their physicians. Follow up questionnaires were sent to patients 6 months later. RESULTS: Of the 295 patients screened, 16.6% (n = 49) had an OSA diagnosis and had been prescribed CPAP. A smaller proportion patients in the diabetes program than in the CRP had discontinued CPAP (22.2% vs 45.2%; P = .03) with discomfort being the greatest barrier. Three of the 7 patients (42.9%) who had contact with their physician resumed CPAP. Of the remaining 246 patients who scored high on >=1 questionnaire (77.6%; n = 191) and returned the 6-month questionnaire (53.9%; n = 103), communication of risk assessment resulted in 49.5% (n = 51) of patients consulting with their physician. Of those, half were referred for polysomnography. All were diagnosed with OSA. CONCLUSION: More than three quarters of patients in diabetes and CRPs scored high on >=1 questionnaire suggesting signs/symptoms of OSA. However, only 16.6% were prescribed CPAP and compliance to treatment was poor (63.3%). Education and communication of OSA risk with patients and physicians resulted in a de novo diagnosis in at least 1 of 10 patients screened and 16.7% restarted CPAP. PMID- 27182761 TI - Physiological Responses of the Modified Shuttle Test in Adults With Cystic Fibrosis. AB - PURPOSE: The modified shuttle test (MST) is increasingly used in clinical practice to assess functional capacity in patients with cystic fibrosis (CF). The purpose of this study was to evaluate the physiological responses of the MST in adults with CF as compared with the gold standard cardiopulmonary exercise test (CPET). METHODS: Participants performed an MST and a CPET on a cycle ergometer in random order. Oxygen (O2) uptake ((Equation is included in full-text article.)O2), carbon dioxide (CO2) retention (end-tidal PCO2; PETCO2), minute ventilation, heart rate, and peripheral O2 saturation (SpO2) were continuously monitored. Whole blood lactate, dyspnea, and leg discomfort were recorded immediately after both exercises. RESULTS: Twenty patients with CF (aged 33 +/- 8 years; forced expiratory volume in 1 second = 48% +/- 17%) completed both tests. Peak values for (Equation is included in full-text article.)O2 (27 +/- 7 vs 24 +/ 6 mL/kg/min), heart rate (169 +/- 19 vs 163 +/- 16 bpm), end PETCO2 (42 +/- 7 vs 39 +/- 8 mm Hg), and O2 desaturation (end SpO2, 86% +/- 7% vs 90% +/- 6%) were significantly higher during the MST than during the CPET (all Ps < .05). Leg discomfort and whole blood lactate were significantly higher after the CPET (both Ps < .05). Thirty-five percent and 40% of patients showed significant O2 desaturation and CO2 retention, respectively, during the MST, which was not detected during the CPET. A strong relationship was found between MST peak (Equation is included in full-text article.)O2 and body weight walking distance product (r = 0.90; P < .01). CONCLUSIONS: The MST may provide a strong indicator of exercise tolerance in adults with CF as indicated by high peak (Equation is included in full-text article.)O2 values. In clinical practice, body weight walking distance should be considered as the primary outcome. This test is also better than cycle ergometry CPET for detecting O2 desaturation and CO2 retention, further emphasizing its clinical interest. PMID- 27182763 TI - Combined Exercise and Inspiratory Muscle Training in Patients With Heart Failure: A SYSTEMATIC REVIEW AND META-ANALYSIS. AB - PURPOSE: Studies have reported the benefits of exercise and inspiratory muscle training (IMT) in patients with heart failure (HF); however, there is no meta analysis on the effects of the combination of exercise and IMT in patients with HF. The objective of this study was to determine whether combined exercise/IMT was more effective than conventional exercise on exercise capacity, respiratory muscle strength, and quality of life in patients with HF. METHODS: This is a systematic review and meta-analysis. We searched MEDLINE, LILACS, CINAHL, EMBASE, PEDro, and the Cochrane Central Register of Controlled Trials (from the earliest date available to April 2015) for randomized controlled trials, examining effects of combined exercise/IMT versus conventional exercise on exercise capacity, respiratory muscle strength, and quality of life measurements in patients with HF. Two reviewers selected studies independently. Weighted mean differences and 95% CIs were calculated. RESULTS: Three studies met the study criteria. Combined exercise/IMT resulted in improvement in maximal inspiratory pressure weighted mean differences (20.89 cm H2O; 95% CI, 14.0-27.78) and Minnesota Living with Heart Failure Questionnaire weighted mean differences (4.43; 95% CI, 0.72-8.14). Nonsignificant difference was observed in peak (Equation is included in full-text article.)O2 for participants in the combined exercise/IMT group compared with the conventional exercise group. No serious adverse events were reported. CONCLUSIONS: Combined exercise/IMT may improve maximal inspiratory pressure and quality of life in patients with HF and should be considered for inclusion in cardiac rehabilitation programs. PMID- 27182762 TI - Insulin Resistance and Diabetes Mellitus in Contemporary Cardiac Rehabilitation. AB - PURPOSE: The goal of this study was to determine the prevalence of insulin resistance (IR) and type 2 diabetes mellitus (T2DM) in contemporary cardiac rehabilitation (CR) and to compare clinical responses in CR between these subsets of patients with coronary heart disease (CHD). METHODS: The study cohort included 818 patients enrolled in CR and separated into 3 groups: (1) individuals with normal hemoglobin A1c (HbA1c) (NoIR: HbA1c < 5.7%); (2) individuals with IR (IR: HbA1c >= 5.7 to <6.5%); (3) and individuals with T2DM (HbA1c >= 6.5%). RESULTS: The combined prevalence of IR (44%) and T2DM (23%) was 67%, which paralleled the prevalence of metabolic syndrome (MetSyn), present in 65% of patients. Women had a higher prevalence of IR and MetSyn than men (73% vs 64%, 72% vs. 63%, respectively) and a greater percentage with an elevated waist circumference (71% vs 60%) (all P < .05). All 3 groups experienced decreases in body weight (NoIR = 2.3 +/- 4.0, IR = -1.7 +/- 4.0, T2DM = -1.0 +/- 4.2 kg) and increases in maximal metabolic equivalents (METs) at exercise testing (NoIR = +2.2 +/- 2.5 vs IR = +2.1 +/- 2.8 vs T2DM = +1.3 +/- 2.3) (all P < .05). Individuals with NoIR achieved greater improvements in weight, body mass index, and METs than patients with T2DM (all P < .05). Selected individuals who participated in a 4-session behavioral weight-loss program lost more than twice the weight as nonparticipants. CONCLUSIONS: The combined prevalence of IR and T2DM in patients with CHD enrolled in CR was remarkably high (67%). To reverse the deleterious consequences of IR and T2DM, targeted interventions involving exercise and weight loss need to be a central focus of CR programming. PMID- 27182765 TI - Cultivating teacher mindfulness: Effects of a randomized controlled trial on work, home, and sleep outcomes. AB - The effects of randomization to a workplace mindfulness training (WMT) or a waitlist control condition on teachers' well-being (moods and satisfaction at work and home), quantity of sleep, quality of sleep, and sleepiness during the day were examined in 2 randomized, waitlist controlled trials (RCTs). The combined sample of the 2 RCTs, conducted in Canada and the United States, included 113 elementary and secondary school teachers (89% female). Measures were collected at baseline, postprogram, and 3-month follow-up; teachers were randomly assigned to condition after baseline assessment. Results showed that teachers randomized to WMT reported less frequent bad moods at work and home, greater satisfaction at work and home, more sleep on weekday nights, better quality sleep, and decreased insomnia symptoms and daytime sleepiness. Training-related group differences in mindfulness and rumination on work at home at postprogram partially mediated the reductions in negative moods at home and increases in sleep quality at follow-up. (PsycINFO Database Record PMID- 27182764 TI - Drawbacks of proactivity: Effects of daily proactivity on daily salivary cortisol and subjective well-being. AB - The benefit of proactive work behaviors for performance-related outcomes has been well established. However, this approach to studying proactivity has not yet acknowledged its potential implications for the actor's well-being. Drawing on the fact that resources at work are limited and that the workplace is a social system characterized by interdependencies, we proposed that daily proactivity could have a negative effect on daily well-being. We furthermore proposed that this effect should be mediated by work overload and negative affect. We conducted a daily diary study (N = 72) to test the potential negative effects of proactivity on daily well-being. Data was collected across 3 consecutive work days. During several daily measurement occasions, participants reported proactivity, work overload, negative affect, and fatigue. They also provided 4 saliva samples per day, from which cortisol was assayed. Based on the 4 samples, a measure of daily cortisol output was produced. Multilevel analyses showed that daily proactivity was positively associated with higher daily cortisol output. The positive association of daily proactivity with bedtime fatigue was marginally significant. There was no support for a mediating effect of work overload and negative affect. Implications for theory-building on the proactivity-well-being link are discussed. (PsycINFO Database Record PMID- 27182766 TI - Attachment of Algal Cells to Zwitterionic Self-Assembled Monolayers Comprised of Different Anionic Compounds. AB - The influence of zwitterionic self-assembled monolayers on settlement and removal of algae was studied. The monolayers were constructed either from zwitterionic thiols or from solutions of positively and negatively charged thiols. The cationic component was composed of quaternary ammonium terminated thiols and the anionic component contained sulfate or carboxylate termination. During assembly, all surfaces showed a strong tendency for equilibration of the surface charge. Settlement and adhesion assays with zoospores of Ulva linza and the diatom Navicula incerta, and field tests of the initial surface colonization revealed the relevance of charge equilibration for the biological inertness of the prepared surfaces. PMID- 27182767 TI - One year test-retest reliability of neurocognitive baseline scores in 10- to 12 year olds. AB - How often youth athletes 10-12 years of age should undergo neurocognitive baseline testing remains an unanswered question. We sought to examine the test retest reliability of annual ImPACT data in a sample of middle school athletes. Participants were 30 youth athletes, ages 10-12 years (Mean = 11.6, SD = 0.6) selected from a larger database of 10-18 year old athletes, who completed two consecutive annual baseline evaluations using the online version of ImPACT. Athlete assent and parental consent were obtained for all participants. Assessments were conducted either individually or in small groups of 2 to 3 athletes, under the supervision of a neuropsychologist or post-doctoral fellow. Test-retest coefficients were as follows: Verbal Memory .71, Visual Memory .35, Visual Motor Speed .69, Reaction Time .34. Intra-class Correlation Coefficients (single/average) were as follows: Verbal Memory .70/.83, Visual Memory .35/.52, Visual Motor Speed .69/.82, Reaction Time .34/.50. Regression-based measures to correct for practice effects revealed that only a small percentage of cases fell outside 90 and 95% confidence intervals, reflecting stability across assessments. Findings indicate that test-retest reliability of Verbal Memory and Visual Motor Speed are generally stable in 10-12 year old athletes. Nevertheless, Visual Memory Index, Reaction Time Index, and Symptom Checklist scores appear to be less reliable over time, especially compared to published data on high school athletes, suggesting the utility of re-testing on an annual basis in this younger age group. PMID- 27182768 TI - ADAMTS4 and Oxidative/Antioxidative Status in Preterm Premature Rupture of Membranes. AB - AIM: To determine the function of a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS4), total oxidant status (TOS), total antioxidant status (TAS), and aryl esterase (ARES) in preterm premature rupture of membranes (PPROM) and to investigate the association with premature rupture of membranes (PROMs). MATERIAL AND METHODS: 58 pregnant women were included in this prospective study which comprised 29 PPROM patients as the study group and 29 patients, having healthy amniotic membranes, as the control group. ADAMTS4, TAS, TOS, and ARES levels were studied in the amniotic membrane homogenates of the patients. RESULTS: ADAMTS4, TAS TOS, and ARES levels of amniotic membrane lysates were significantly different between PPROM and control groups (p < 0.001, p < 0.001, p = 0.008 and p = 0.002, respectively). Increased amniotic membrane ADAMTS4 (OR: 1.051 95% CI 1.006-1.098, p = 0.024) and TOS (OR: 12.777 95% CI 1.595-102.323, p = 0.016) were found to be significantly associated with the increased risk of PPROM. CONCLUSION: ADAMTS4, TOS, and ARES levels were higher and TAS level was lower in PPROM patients than the normal healthy control group which had healthy amniotic membranes at term. As a result, ADAMTS4 may have a role in the pathogenesis by causing increased oxidative and inflammatory environment in PPROM. PMID- 27182770 TI - Determination of Aroma Compound Partition Coefficients in Aqueous, Polysaccharide, and Dairy Matrices Using the Phase Ratio Variation Method: A Review and Modeling Approach. AB - The partition of aroma compounds between a matrix and a gas phase describes an individual compound's specific affinity toward the matrix constituents affecting orthonasal sensory perception. The static headspace phase ratio variation (PRV) method has been increasingly applied by various authors to determine the equilibrium partition coefficient K in aqueous, polysaccharide, and dairy matrices. However, reported partition coefficients are difficult to relate and compare due to different experimental conditions, e.g., aroma compound selection, matrix composition, equilibration temperature. Due to its specific advantages, the PRV method is supposed to find more frequent application in the future, this Review aims to summarize, evaluate, compare, and relate the currently available data on PRV-determined partition coefficients. This process was designed to specify the potentials and the limitations as well as the consistency of the PRV method, and to identify open fields of research in aroma compound partitioning in food-related, especially dairy matrices. PMID- 27182771 TI - IBD LIVE Case Series-Case 4: Worms in IBD: Friend or Foe. PMID- 27182769 TI - Clozapine administration in clinical practice: once-daily versus divided dosing. AB - OBJECTIVE: While it is recommended that clozapine be administered in a divided dosing regimen, it is unclear whether this recommendation is followed in real world clinical practice. In two large datasets, we examined clozapine dosing frequency and patient characteristics across different dosing regimens. METHOD: We conducted a cross-sectional survey, collecting data on patients receiving clozapine in August/September 2015 from the Centre for Addiction and Mental Health (CAMH) in Toronto, Canada, and The Zucker Hillside Hospital (ZHH) in New York, United States. RESULTS: Of 676 and 308 patients included in CAMH and ZHH datasets, clozapine was prescribed once daily in 75.1% and 74.4%, even though doses exceeding 200 mg/day were administered in 88.6% and 84.4% of the respective samples. No significant difference was found in the rates of positive symptom remission between once-daily vs. divided dosing (79.7% vs. 80.5%, P = 1.00). Higher clozapine dose and use of anticholinergic medications were significantly associated with divided dosing in both datasets. Older age or male gender was related to divided dosing in CAMH or ZHH dataset respectively. CONCLUSION: Despite the product monograph recommendation, clozapine is frequently prescribed once daily in North America. Further studies are needed to compare clinical outcomes between once-daily vs. divided clozapine dosing. PMID- 27182772 TI - Coronary artery disease in outpatients with nonvalvular atrial fibrillation: results from the multicenter RAMSES study. AB - BACKGROUND: Nonvalvular atrial fibrillation (NVAF) frequently coexists with coronary artery disease (CAD). However, the optimal antithrombotic strategy for patients with concomitant CAD and NVAF is controversial. The aim of this study is to assess the prevalence of CAD with NVAF and to determine antithrombotic treatment options in patients with or without a history of CAD. METHODS: ReAl life Multicenter Survey Evaluating Stroke prevention strategies in Turkey (RAMSES study) was a cross-sectional, multicenter, nationwide observational study carried out in NVAF patients. We studied the clinical data of 6264 Turkish patients participating in the RAMSES study. Demographic properties and antithrombotic therapies were recorded and compared between patients with and without CAD. RESULTS: CAD was present in 1828 (29.2%) of patients with NVAF. Most of the NVAF patients with CAD were men (58%) and comorbid diseases were significantly more common in patients with CAD. Although patients with CAD had higher CHA2DS2VASc scores than those without disease (4.1+/-1.5 vs. 2.9+/-1.5; P=0.001), they had lower use of oral anticoagulant (OAC) therapy (66.1 vs. 74.4%, P=0.01). Among OAC drugs, warfarin was the preferred medication in patients with CAD (35.4 vs. 30.6%, P=0.01), whereas nonvitamin K antagonist oral anticoagulants were preferred in patients without CAD (40 vs. 34.3%, P=0.01). Patients with CAD required nearly three-fold higher antiplatelet treatment compared with patients without CAD (57.8 vs. 21.4%, P<0.001). CONCLUSION: CAD affects nearly one-third of patients with NVAF in a real-world setting. Although they merit more aggressive therapy, patients with CAD and NVAF were less likely to receive OAC therapy. PMID- 27182773 TI - Epidemic and Non-Epidemic Hot Spots of Malaria Transmission Occur in Indigenous Comarcas of Panama. AB - From 2002-2005, Panama experienced a malaria epidemic that has been associated with El Nino Southern Oscillation weather patterns, decreased funding for malaria control, and landscape modification. Case numbers quickly decreased afterward, and Panama is now in the pre-elimination stage of malaria eradication. To achieve this new goal, the characterization of epidemiological risk factors, foci of transmission, and important anopheline vectors is needed. Of the 24,681 reported cases in these analyses (2000-2014), ~62% occurred in epidemic years and ~44% in indigenous comarcas (5.9% of Panama's population). Sub-analyses comparing overall numbers of cases in epidemic and non-epidemic years identified females, comarcas and some 5-year age categories as those disproportionately affected by malaria during epidemic years. Annual parasites indices (APIs; number of cases per 1,000 persons) for Plasmodium vivax were higher in comarcas compared to provinces for all study years, though P. falciparum APIs were only higher in comarcas during epidemic years. Interestingly, two comarcas report increasing numbers of cases annually, despite national annual decreases. Inclusion of these comarcas within identified foci of malaria transmission confirmed their roles in continued transmission. Comparison of species distribution models for two important anophelines with Plasmodium case distribution suggest An. albimanus is the primary malaria vector in Panama, confirmed by identification of nine P. vivax infected specimen pools. Future malaria eradication strategies in Panama should focus on indigenous comarcas and include both active surveillance for cases and comprehensive anopheline vector surveys. PMID- 27182774 TI - Improved Detection of Circulating Tumor Cells in Metastatic Colorectal Cancer by the Combination of the CellSearch(r) System and the AdnaTest(r). AB - Colorectal cancer (CRC) is one of the major causes of cancer-related death and reliable blood-based prognostic biomarkers are urgently needed. The enumeration and molecular characterization of circulating tumor cells (CTCs) has gained increasing interest in clinical practice. CTC detection by CellSearch(r) has already been correlated to an unfavorable outcome in metastatic CRC. However, the CTC detection rate in mCRC disease is low compared to other tumor entities. Thus, the use of alternative (or supplementary) assays might help to itemize the prognostic use of CTCs as blood-based biomarkers. In this study, blood samples from 47 mCRC patients were screened for CTCs using the FDA-cleared CellSearch(r) technology and / or the AdnaTest(r). 38 samples could be processed in parallel. We demonstrate that a combined analysis of CellSearch(r) and the AdnaTest(r) leads to an improved detection of CTCs in our mCRC patient cohort (positivity rate CellSearch(r) 33%, AdnaTest(r) 30%, combined 50%). While CTCs detected with the CellSearch(r) system were significantly associated with progression-free survival (p = 0.046), a significant correlation regarding overall survival could be only seen when both assays were combined (p = 0.013). These findings could help to establish improved tools to detect CTCs as on-treatment biomarkers for clinical routine in future studies. PMID- 27182776 TI - Cold-Water Corals and Anthropogenic Impacts in La Fonera Submarine Canyon Head, Northwestern Mediterranean Sea. AB - We assess the occurrence and extent of cold-water coral (CWC) species Madrepora oculata and Dendrophyllia cornigera, as well as gorgonian red coral Corallium rubrum, in La Fonera canyon head (Northwestern Mediterranean Sea), as well as human impacts taking place in their habitats. Occurrence is assessed based on Remotely Operated Vehicle (ROV) video imaging. Terrain classification techniques are applied to high-resolution swath bathymetric data to obtain semi-automatic interpretative maps to identify the relationship between coral distribution patterns and canyon environments. A total of 21 ROV immersions were carried out in different canyon environments at depths ranging between 79 and 401 m. Large, healthy colonies of M. oculata occur on abrupt, protected, often overhanging, rocky sections of the canyon walls, especially in Illa Negra branch. D. cornigera is sparser and evenly distributed at depth, on relatively low sloping areas, in rocky but also partially sedimented areas. C. rubrum is most frequent between 100 and 160 m on highly sloping rocky areas. The probable extent of CWC habitats is quantified by applying a maximum entropy model to predict habitat suitability: 0.36 km2 yield M. oculata occurrence probabilities over 70%. Similar predictive models have been produced for D. cornigera and C. rubrum. All ROV transects document either the presence of litter on the seafloor or pervasive trawling marks. Nets and longlines are imaged entangled on coral colonies. Coral rubble is observed at the foot of impacted colonies. Some colonies are partially covered by sediment that could be the result of the resuspension generated by bottom trawling on neighbouring fishing grounds, which has been demonstrated to be responsible of daily increases in sediment fluxes within the canyon. The characteristics of the CWC community in La Fonera canyon are indicative that it withstands high environmental stress of both natural and human origin. PMID- 27182775 TI - Characterization of Novel Hepatitis B Virus PreS/S-Gene Mutations in a Patient with Occult Hepatitis B Virus Infection. AB - OBJECTIVE: The impact of hepatitis B virus (HBV) preS/S-gene mutations on occult HBV infection (OBI) is not fully understood. This study characterized multiple novel HBV preS/S-gene mutants obtained from an OBI patient. METHODS: PreS/S-gene mutants were analyzed by clonal sequencing. Viral replication and expression were analyzed by transfecting HBV genomic recombinants into HepG2 cells. RESULTS: Twenty-one preS/S-gene mutants were cloned from four sequential serum samples, including 13 mutants that were not previously documented: (1) sI/T126V+sG145R; (2) preS1 nt 3014-3198 deletion; (3) preS1 nt 3046-3177 deletion; (4) preS1 nt 3046-3177 deletion+s115-116 "INGTST" insertion; (5) preS1 nt 3046-3177 deletion+s115-116 "INGTST" insertion+sG145R; (6) preS1 nt 3115-3123 deletion+sQ129N; (7) preS1 nt 3115-3123 deletion+s126-127 "RPCMNCTI" insertion; (8) s115-116 "INGTST" insertion; (9) s115-116 "INGTST" insertion+sG145R; (10) s126-127 "RPCMNCTI" insertion; (11) preS1 nt 2848-2862 deletion+preS2 initiation codon M->I; (12) s122-123 "KSTGLCK" insertion+sQ129N; and (13) preS2 initiation codon M->I+s131-133TSM->NST. The proportion of preS1 nt 3046-3177 deletion and preS2 initiation codon M->I+s131-133TSM->NST mutants increased in the viral pool with prolonged disease. The 13 novel OBI-related mutants showed a 51.2-99.9% decrease in HBsAg levels compared with that of the wild type. Additional N glycosylation-associated mutations, sQ129N and s131-133TSM->NST, but not s126-127 "RPCMNCTI," greatly attenuated anti-HBs binding to HBsAg. Compared with the wild type, replication and surface antigen promoter II activity of the preS1 nt 3046 3177 deletion mutant decreased by 43.3% and 97.0%, respectively. CONCLUSION: PreS/S-gene mutations may play coordinated roles in the presentation of OBI and might be associated with disease progression. This has implications for HBV diagnosis and vaccine improvement. PMID- 27182777 TI - Multifunctional and Continuous Gradients of Biointerfaces Based on Dual Reverse Click Reactions. AB - Chemical or biological gradients that are composed of multifunctional and/or multidirectional guidance cues are of fundamental importance for prospective biomaterials and biointerfaces. As a proof of concept, a general modification approach for generating multifunctional and continuous gradients was realized via two controlled and reversed click reactions, namely, thermo-activated thiol-yne and copper-free alkyne and azide click reactions. The cell adhesion property of fibroblasts was guided in a gradient with an enhancement, showing that the PEG molecule and RGD peptide were countercurrently immobilized to form such reversed gradients (with negating of the cell adhesion property). Using the gradient modification protocol to also create countercurrent distributions of FGF-2 and BMP-2 gradients, the demonstration of not only multifunctional but also gradient biointerfacial properties was resolved in time latencies on one surface by showing the manipulation in gradients toward proliferation and osteogenic differentiation for adipose-derived stem cells. PMID- 27182778 TI - Novel Luminex Assay for Telomere Repeat Mass Does Not Show Well Position Effects Like qPCR. AB - Telomere length is a potential biomarker of aging and risk for age-related diseases. For measurement of relative telomere repeat mass (TRM), qPCR is typically used primarily due to its low cost and low DNA input. But the position of the sample on a plate often impacts the qPCR-based TRM measurement. Recently we developed a novel, probe-based Luminex assay for TRM that requires ~50ng DNA and involves no DNA amplification. Here we report, for the first time, a comparison among TRM measurements obtained from (a) two singleplex qPCR assays (using two different primer sets), (b) a multiplex qPCR assay, and (c) our novel Luminex assay. Our comparison is focused on characterizing the effects of sample positioning on TRM measurement. For qPCR, DNA samples from two individuals (K and F) were placed in 48 wells of a 96-well plate. For each singleplex qPCR assay, we used two plates (one for Telomere and one for Reference gene). For the multiplex qPCR and the Luminex assay, the telomere and the reference genes were assayed from the same well. The coefficient of variation (CV) of the TRM for Luminex (7.2 to 8.4%) was consistently lower than singleplex qPCR (11.4 to 14.9%) and multiplex qPCR (19.7 to 24.3%). In all three qPCR assays the DNA samples in the left- and right-most columns showed significantly lower TRM than the samples towards the center, which was not the case for the Luminex assay (p = 0.83). For singleplex qPCR, 30.5% of the variation in TL was explained by column-to-column variation and 0.82 to 27.9% was explained by sample-to-sample variation. In contrast, only 5.8% of the variation in TRM for the Luminex assay was explained by column-to column variation and 50.4% was explained by sample-to-sample variation. Our novel Luminex assay for TRM had good precision and did not show the well position effects of the sample that were seen in all three of the qPCR assays that were tested. PMID- 27182779 TI - Microleakage under ceramic flash-free orthodontic brackets after thermal cycling. AB - OBJECTIVE: To compare microleakage under 3M Unitek's APC Flash-Free Adhesive Coated System bracket and the APC PLUS Adhesive Coated System bracket after thermal cycling. MATERIALS AND METHODS: Forty freshly extracted human maxillary premolars were randomly divided into two groups and bonded with either a Flash Free bracket or a PLUS bracket. After bonding, the samples were incubated in a water bath at 37 degrees C for 24 hours and thermocycled for 5000 cycles between 5 degrees C and 50 degrees C. All teeth were immersed in a 2% methylene blue solution for 24 hours, embedded in acrylic and sectioned in a buccolingual direction at approximately the center of the bracket. Microleakage was observed at the enamel-adhesive interface from the occlusal and gingival margins of the bracket base. Statistical analysis was conducted using the Mann-Whitney U-test. RESULTS: The median microleakage was higher in the Flash-Free group, but the difference between the two groups was not statistically significant (P > .05). CONCLUSION: In a laboratory setting, there is no significant difference between the extent of microleakage under the APC Flash-Free Adhesive Coated System bracket and the APC PLUS Adhesive Coated System bracket after thermal cycling. PMID- 27182780 TI - Assessment of vertical changes during maxillary expansion using quad helix or bonded rapid maxillary expander. AB - OBJECTIVE: To determine if there is a significantly different effect on vertical changes during phase I palatal expansion treatment using a quad helix and a bonded rapid maxillary expander in growing skeletal Class I and Class II patients. MATERIALS AND METHODS: This retrospective study looked at 2 treatment groups, a quad helix group and a bonded rapid maxillary expander group, before treatment (T1) and at the completion of phase I treatment (T2). Each treatment group was compared to an untreated predicted growth model. Lateral cephalograms at T1 and T2 were traced and analyzed for changes in vertical dimension. RESULTS: No differences were found between the treatment groups at T1, but significant differences at T2 were found for convexity, lower facial height, total facial height, facial axis, and Frankfort Mandibular Plane Angle (FMA) variables. A comparison of treatment groups at T2 to their respective untreated predicted growth models found a significant difference for the lower facial height variable in the quad helix group and for the upper first molar to palatal plane (U6-PP) variable in the bonded expander group. CONCLUSION: Overall, both the quad helix expander and the bonded rapid maxillary expander showed minimal vertical changes during palatal expansion treatment. The differences at T2 suggested that the quad helix expander had more control over skeletal vertical measurements. When comparing treatment results to untreated predicted growth values, the quad helix expander appeared to better maintain lower facial height and the bonded rapid maxillary expander appeared to better maintain the maxillary first molar vertical height. PMID- 27182781 TI - Dynamic smile evaluation in different skeletal patterns. AB - OBJECTIVE: To evaluate dynamic smile in different skeletal patterns and to correlate vertical smile parameters with the underlying causative factors. MATERIALS AND METHODS: A total of 150 participants ranging in age from 16-25 years were selected and divided into one of three groups-horizontal, average, and vertical skeletal pattern-using the following three cephalometric parameters: SN MP, FMA, and Jarabak ratio. Videographic records of smile were obtained, and measurements were recorded and analyzed at rest, including upper lip length, and during smile, including maxillary incisal display, interlabial gap, intercommisural width, change in upper lip length, and smile arc. Differences among the three groups were subjected to two-way analysis of variance and post hoc and chi-square tests for smile arc. Correlations between vertical smile variables and vertical skeletal (N-ANS, N-Me) and dental cephalometric measurements (U1 to palatal plane) were also investigated. RESULTS: Vertical parameters were significantly increased in the vertical pattern when compared with the horizontal pattern, ie, upper lip length (P < .01), maxillary incisal display (P < .001), interlabial gap (P < .001), and change in upper lip length (P < .001), whereas intercommisural width was significantly decreased in vertical pattern when compared with the horizontal pattern (P < .001). Flat smile arc was seen more frequently in the horizontal pattern. Positive correlations were found between the N-Me, U1-PP, and change in upper lip length with vertical smile parameters. CONCLUSIONS: Different skeletal patterns exhibit their characteristic smile features. Upper lip length is not responsible for increased incisal display during smile. Increased incisal display during smile is more closely associated with upper lip elevation than vertical skeletal and dental factors. PMID- 27182782 TI - High-Dose Desflurane for Tocolysis During Intrapartum Myelomeningocele Repair in a Patient With Post-Adriamycin Cardiomyopathy. AB - High-dose desflurane is an uncommon need during general anesthesia. At our institution, open fetal surgery cases are managed with high desflurane concentrations to ensure uterine relaxation. We present a case of a 32-year-old parturient with a history of mild cardiomyopathy undergoing open fetal myelomeningocele repair. Phenylephrine and dopamine infusions helped maintain hemodynamic stability at 18% desflurane, while cardiac function was monitored with transthoracic echocardiography. This case is notable for the unknown risk of using high-dose desflurane with a preexisting cardiomyopathy and raises the question of the acceptable maternal risk in the setting of fetal surgery. PMID- 27182783 TI - Normative influences on the nonmedical use of prescription stimulants among college students. AB - Recent epidemiological data indicate an increasing trend in the nonmedical use of prescription drugs among college students. The nonmedical use of prescription drugs involves using a prescription medication without a prescription, or using the medication in a manner inconsistent with a health care provider's instructions. Among college students, prescription stimulants have the highest ratio of nonmedical to medical use and the highest rate of illicit selling and trading on college campuses. The increased prevalence is accompanied by increased risk, as 18-25-year-olds have the highest rate of emergency department visits for nonmedical use of prescription stimulants (NMUPS). To date, no study has examined the impact of social norms on NMUPS. The social norm theory has accounted for other health related behaviors (e.g., alcohol and marijuana use) and has been utilized in brief interventions targeting risky health behaviors. The current study examined the prevalence of self-reported NMUPS among college students and the impact of perceived social norms on NMUPS. The current study included 959 participants who completed an online survey that assessed for NMUPS, self approval for NMUPS, and perceived descriptive and injunctive norms for NMUPS. Similar to previous research on alcohol and marijuana use, students overestimated the prevalence of NMUPS and this overestimation was related to past-year NMUPS. Perceived close friend and parental approval of NMUPS was positively related to self-approval and past-year NMUPS. Overall, the study broadens the existing literature on NMUPS and provides a platform for developing brief interventions that target this risky behavior. (PsycINFO Database Record PMID- 27182784 TI - A Qualitative Study Exploring Moral Distress Among Pediatric Resuscitation Team Clinicians: Challenges to Professional Integrity. AB - OBJECTIVE: Our study objectives were to explore moral distress among pediatric team clinicians within the context of resuscitation experiences, and determine whether there were any distinctively ethical perspectives on moral distress that could be conceptualized as challenges to professional integrity, rather than to previously described psychological responses of clinicians. DESIGN: Descriptive, exploratory qualitative study. SETTING: A large tertiary pediatric academic hospital in Houston, TX. SUBJECTS: Twenty-five PICU resuscitation team clinicians were interviewed from December 2012 to April 2013. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All clinicians reported experiencing moral distress during certain resuscitations. Twenty-one of 25 clinicians reflected and acknowledged that their sense of professional integrity had been challenged during those resuscitation events. Four main components of resuscitation experience that induced moral distress were identified: 1) experiences where there was lack of understanding of the big picture; 2) experiences where there was suboptimal team leadership; 3) experiences where there was variable meanings to the word "resuscitation"; and 4) experiences were there was uncertainty of role responsibility. CONCLUSIONS: The perception of moral distress exists among pediatric clinicians during resuscitations and could be conceptualized as challenges to professional integrity. This ethical framework offers an alternative approach to understanding and investigating the complex layers of moral distress. PMID- 27182785 TI - HPV vaccination in Southern Africa: A jab of hope in the fight against cervical cancer. PMID- 27182786 TI - Socioecological correlates of clinical signs in two communities of wild chimpanzees (Pan troglodytes) at Gombe National Park, Tanzania. AB - Disease and other health hazards pose serious threats to the persistence of wild ape populations. The total chimpanzee population at Gombe National Park, Tanzania, has declined from an estimated 120 to 150 individuals in the 1960's to around 100 individuals by the end of 2013, with death associated with observable signs of disease as the leading cause of mortality. In 2004, we began a non invasive health-monitoring program in the two habituated communities in the park (Kasekela and Mitumba) with the aim of understanding the prevalence of health issues in the population, and identifying the presence and impacts of various pathogens. Here we present prospectively collected data on clinical signs (observable changes in health) in the chimpanzees of the Kasekela (n = 81) and Mitumba (n = 32) communities over an 8-year period (2005-2012). First, we take a population approach and analyze prevalence of clinical signs in five different categories: gastrointestinal system (diarrhea), body condition (estimated weight loss), respiratory system (coughing, sneezing etc.), wounds/lameness, and dermatologic issues by year, month, and community membership. Mean monthly prevalence of each clinical sign per community varied, but typically affected <10% of observed individuals. Secondly, we analyze the presence of clinical signs in these categories as they relate to individual demographic and social factors (age, sex, and dominance rank) and simian immunodeficiency virus (SIVcpz) infection status. Adults have higher odds of being observed with diarrhea, loss of body condition, and wounds or lameness when compared to immatures, while males have a higher probability of being observed with wounds or lameness than females. In contrast, signs of respiratory illness appear not to be related to chimpanzee specific factors and skin abnormalities are very rare. For a subset of known-rank individuals, dominance rank predicts the probability of wounding/lameness in adult males, but does not predict any adverse clinical signs in adult females. Instead, adult females with SIVcpz infection are more likely to be observed with diarrhea, a finding that warrants further investigation. Comparable data are needed from other sites to determine whether the prevalence of clinical signs we observe are relatively high or low, as well as to more fully understand the factors influencing health of wild apes at both the population and individual level. Am. J. Primatol. 80:e22562, 2018. (c) 2016 Wiley Periodicals, Inc. PMID- 27182787 TI - Proton Conduction in a Phosphonate-Based Metal-Organic Framework Mediated by Intrinsic "Free Diffusion inside a Sphere". AB - Understanding the molecular mechanism of proton conduction is crucial for the design of new materials with improved conductivity. Quasi-elastic neutron scattering (QENS) has been used to probe the mechanism of proton diffusion within a new phosphonate-based metal-organic framework (MOF) material, MFM-500(Ni). QENS suggests that the proton conductivity (4.5 * 10(-4) S/cm at 98% relative humidity and 25 degrees C) of MFM-500(Ni) is mediated by intrinsic "free diffusion inside a sphere", representing the first example of such a mechanism observed in MOFs. PMID- 27182789 TI - Cluster Evolution at Early Stages of 1,3,5-Triamino-2,4,6-trinitrobenzene under Various Heating Conditions: A Molecular Reactive Force Field Study. AB - We carried out reactive molecular dynamics simulations by ReaxFF to study the initial events of an insensitive high explosive 1,3,5-triamino-2,4,6 trinitrobenzene (TATB) against various thermal stimuli including constant temperature heating, programmed heating, and adiabatic heating to simulate TATB suffering from accidental heating in reality. Cluster evolution at the early stage of the thermal decomposition of condensed TATB was the main focus as cluster formation primarily occurs when TATB is heated. The results show that cluster formation is the balance of the competition of intermolecular collision and molecular decomposition of TATB, that is, an appropriate temperature and certain duration are required for cluster formation and preservation. The temperature in the range of 2000-3000 K was found to be optimum for fast formation and a period of preservation. Besides, the intra- and intermolecular H transfers are always favorable, whereas the C-NO2 partition was favorable at high temperature. The simulation results are helpful to deepen the insight into the thermal properties of condensed TATB. PMID- 27182788 TI - Adherence to ARRIVE Guidelines in Chinese Journal Reports on Neoplasms in Animals. AB - BACKGROUND: The Animals in Research: Reporting In Vivo Experiments (ARRIVE) guidelines were published in 2010 with the aim of improving the quality of studies involving animals. However, how well Chinese studies involving animal neoplasms adhere to these guidelines has not been assessed. OBJECTIVE: To evaluate the reporting quality of such experiments published between 2010 and 2012 in Chinese journals with support from the National Natural Science Foundation of China. METHODS: We searched the Chinese Science Citation and Chinese Journal Full-Text Databases for articles published between 2010 and 2012 involving neoplasms in animals. The data were extracted into pre-prepared forms. Reporting quality was assessed using the ARRIVE checklist-39 items plus information on blinding. RESULTS: Three hundred and ninety-six animal studies were included in the analysis: 127 studies published in 2010, 140 studies published in 2011, and 129 studies published in 2012. The range of ARRIVE score is from 12 to 27 with a maximum possible score of 40. Studies published in 2012 (P = 0.012), 2011 (P = 0.015), 2010, July~Dec (P<0.017) had a significantly larger ARRIVE checklist score than those published in Jan.~June, 2010, respectively. CONCLUSIONS: Experiments involving neoplasms in animals published in Chinese journals generally have not comprehensively reported the information recommended by the ARRIVE guidelines. We strongly recommend that researchers conducting such studies report this information. PMID- 27182790 TI - Medicaid Coverage and Access to Care for American Indians and Alaska Natives Under the Affordable Care Act. PMID- 27182791 TI - Global sensitivity analysis and Bayesian parameter inference for solute transport in porous media colonized by biofilms. AB - The concept of dual flowing continuum is a promising approach for modeling solute transport in porous media that includes biofilm phases. The highly dispersed transit time distributions often generated by these media are taken into consideration by simply stipulating that advection-dispersion transport occurs through both the porous and the biofilm phases. Both phases are coupled but assigned with contrasting hydrodynamic properties. However, the dual flowing continuum suffers from intrinsic equifinality in the sense that the outlet solute concentration can be the result of several parameter sets of the two flowing phases. To assess the applicability of the dual flowing continuum, we investigate how the model behaves with respect to its parameters. For the purpose of this study, a Global Sensitivity Analysis (GSA) and a Statistical Calibration (SC) of model parameters are performed for two transport scenarios that differ by the strength of interaction between the flowing phases. The GSA is shown to be a valuable tool to understand how the complex system behaves. The results indicate that the rate of mass transfer between the two phases is a key parameter of the model behavior and influences the identifiability of the other parameters. For weak mass exchanges, the output concentration is mainly controlled by the velocity in the porous medium and by the porosity of both flowing phases. In the case of large mass exchanges, the kinetics of this exchange also controls the output concentration. The SC results show that transport with large mass exchange between the flowing phases is more likely affected by equifinality than transport with weak exchange. The SC also indicates that weakly sensitive parameters, such as the dispersion in each phase, can be accurately identified. Removing them from calibration procedures is not recommended because it might result in biased estimations of the highly sensitive parameters. PMID- 27182792 TI - Predicting groundwater redox status on a regional scale using linear discriminant analysis. AB - Reducing conditions are necessary for denitrification, thus the groundwater redox status can be used to identify subsurface zones where potentially significant nitrate reduction can occur. Groundwater chemistry in two contrasting regions of New Zealand was classified with respect to redox status and related to mappable factors, such as geology, topography and soil characteristics using discriminant analysis. Redox assignment was carried out for water sampled from 568 and 2223 wells in the Waikato and Canterbury regions, respectively. For the Waikato region 64% of wells sampled indicated oxic conditions in the water; 18% indicated reduced conditions and 18% had attributes indicating both reducing and oxic conditions termed "mixed". In Canterbury 84% of wells indicated oxic conditions; 10% were mixed; and only 5% indicated reduced conditions. The analysis was performed over three different well depths, <25m, 25 to 100 and >100m. For both regions, the percentage of oxidised groundwater decreased with increasing well depth. Linear discriminant analysis was used to develop models to differentiate between the three redox states. Models were derived for each depth and region using 67% of the data, and then subsequently validated on the remaining 33%. The average agreement between predicted and measured redox status was 63% and 70% for the Waikato and Canterbury regions, respectively. The models were incorporated into GIS and the prediction of redox status was extended over the whole region, excluding mountainous land. This knowledge improves spatial prediction of reduced groundwater zones, and therefore, when combined with groundwater flow paths, improves estimates of denitrification. PMID- 27182793 TI - Explaining Racial Disparities in Child Asthma Readmission Using a Causal Inference Approach. AB - IMPORTANCE: Childhood asthma is characterized by disparities in the experience of morbidity, including the risk for readmission to the hospital after an initial hospitalization. African American children have been shown to have more than 2 times the hazard of readmission when compared with their white counterparts. OBJECTIVE: To explain why African American children are at greater risk for asthma-related readmissions than white children. DESIGN, SETTING, AND PARTICIPANTS: This study was completed as part of the Greater Cincinnati Asthma Risks Study, a population-based, prospective, observational cohort. From August 2010 to October 2011, it enrolled 695 children, aged 1 to 16 years, admitted for asthma or wheezing who identified as African American (n = 441) or white (n = 254) in an inpatient setting of an urban, tertiary care children's hospital. MAIN OUTCOMES AND MEASURES: The main outcome was time to asthma-related readmission and race was the predictor. Biologic, environmental, disease management, access, and socioeconomic hardship variables were measured; their roles in understanding racial readmission disparities were conceptualized using a directed acyclic graphic. Inverse probability of treatment weighting balanced African American and white children with respect to key measured variables. Racial differences in readmission hazard were assessed using weighted Cox proportional hazards regression and Kaplan-Meier curves. RESULTS: The sample was 65% male (n = 450), and the median age was 5.4 years. African American children were 2.26 times more likely to be readmitted than white children (95% CI, 1.56-3.26). African American children significantly differed with respect to nearly every measured biologic, environmental, disease management, access, and socioeconomic hardship variable. Socioeconomic hardship variables explained 53% of the observed disparity (hazard ratio, 1.47; 95% CI, 1.05-2.05). The addition of biologic, environmental, disease management, and access variables resulted in 80% of the readmission disparity being explained. The difference between African American and white children with respect to readmission hazard no longer reached the level of significance (hazard ratio, 1.18; 95% CI, 0.87-1.60; Cox P = .30 and log-rank P = .39). CONCLUSIONS AND RELEVANCE: A total of 80% of the observed readmission disparity between African American and white children could be explained after statistically balancing available biologic, environmental, disease management, access to care, and socioeconomic and hardship variables across racial groups. Such a comprehensive, well-framed approach to exposures that are associated with morbidity is critical as we attempt to better understand and lessen persistent child asthma disparities. PMID- 27182795 TI - Intergenerational educational trajectories and lower back pain in young women and men. AB - We examined the association between intergenerational educational trajectories and lower back pain (LBP) outcomes in young women and men from the general population. Participants were part of the 21 years old follow-up of the EPITeen cohort study, which was set up during the 2003/2004 school year and recruited subjects born in 1990 attending schools in Porto, Portugal (n=1657, 51.6% women). Parental and individual educational levels were used to define intergenerational educational trajectories as stable-high, upward, stable-low, and downward. Data on the presence, severity and chronicity of LBP were also assessed. Gender specific adjusted odds ratios (OR) with 95% confidence intervals (95% CI) were computed to estimate the associations between educational trajectories and LBP outcomes. When compared to women with stable-high educational trajectories, those with stable-low educational trajectories were significantly more likely to report moderate/severe (adjusted OR=1.76, 95% CI: 1.21-2.57) and chronic (adjusted OR=1.82, 95% CI: 1.02-3.22) LBP. The magnitude of these associations was even stronger among females with downward educational trajectories (moderate/severe: adjusted OR=2.58, 95% CI: 1.49-4.46; chronic: adjusted OR=2.42, 95% CI: 1.12 5.27). Educational trajectories were not significantly associated to LBP outcomes among men. In conclusion, intergenerational educational trajectories may contribute to LBP as reported in early adulthood, particularly in women. PMID- 27182796 TI - Solid State Collapse of a High-Spin Square-Planar Fe(II) Complex, Solution Phase Dynamics, and Electronic Structure Characterization of an Fe(II)2 Dimer. AB - Square-planar high-spin Fe(II) molecular compounds are rare, and until recently, the only four examples of non-macrocyclic or sterically driven molecular compounds of this kind shared a common FeO4 core. The trianionic pincer-type ligand [CF3-ONO]H3 (1) supports the high-spin square-planar Fe(II) complex {[CF3 ONO]FeCl}{Li(Sv)2}2 (2). In the solid state, 2 forms the dimer complex {[CF3 ONO]Fe}2{(MU-Cl)2(MU-LiTHF)4} (3) in 96% yield by simply applying a vacuum or stirring it with pentane for 2 h. A detailed high-frequency electron paramagnetic resonance and field-dependent (57)Fe Mossbauer investigation of 3 revealed a weak antiferromagnetic exchange interaction between the local iron spins which exhibit a zero-field splitting tensor characterized by negative D parameter. In solution, 2 is in equilibrium with the solvento complex {[CF3-ONO]FeCl(THF)}{Li2(Sv)4} (2.Sv) and the dimer 3. A combination of frozen solution (57)Fe Mossbauer spectroscopy and single crystal X-ray crystallography helped elucidate the solvent dependent equilibrium between these three species. The oxidation chemistry of 2.Sv was investigated. Complex 2 reacts readily with the one electron oxidizing agent CuCl2 to give the Fe(III) complex {[CF3 ONO]FeCl2}{Li(THF)2}2 (4). Also, 2.Sv reacts with 2 equiv of TlPF6 to form the Fe(III) complex [CF3-ONO]Fe(THF)3 (5). PMID- 27182794 TI - Abrus Agglutinin, a type II ribosome inactivating protein inhibits Akt/PH domain to induce endoplasmic reticulum stress mediated autophagy-dependent cell death. AB - Abrus agglutinin (AGG), a type II ribosome-inactivating protein has been found to induce mitochondrial apoptosis. In the present study, we documented that AGG mediated Akt dephosphorylation led to ER stress resulting the induction of autophagy-dependent cell death through the canonical pathway in cervical cancer cells. Inhibition of autophagic death with 3-methyladenine (3-MA) and siRNA of Beclin-1 and ATG5 increased AGG-induced apoptosis. Further, inhibiting apoptosis by Z-DEVD-FMK and N-acetyl cysteine (NAC) increased autophagic cell death after AGG treatment, suggesting that AGG simultaneously induced autophagic and apoptotic death in HeLa cells. Additionally, it observed that AGG-induced autophagic cell death in Bax knock down (Bax-KD) and 5-FU resistant HeLa cells, confirming as an alternate cell killing pathway to apoptosis. At the molecular level, AGG-induced ER stress in PERK dependent pathway and inhibition of ER stress by salubrinal, eIF2alpha phosphatase inhibitor as well as siPERK reduced autophagic death in the presence of AGG. Further, our in silico and colocalization study showed that AGG interacted with pleckstrin homology (PH) domain of Akt to suppress its phosphorylation and consequent downstream mTOR dephosphorylation in HeLa cells. We showed that Akt overexpression could not augment GRP78 expression and reduced autophagic cell death by AGG as compared to pcDNA control, indicating Akt modulation was the upstream signal during AGG's ER stress mediated autophagic cell death. In conclusion, we established that AGG stimulated cell death by autophagy might be used as an alternative tumor suppressor mechanism in human cervical cancer. (c) 2016 Wiley Periodicals, Inc. PMID- 27182797 TI - Synthesis and Structure of Cyclic Trisaccharide with Expanded Glycosidic Linkages. AB - A new cyclic trisaccharide is synthesized by cycloglycosylation of a linear trisaccharide, modified with hydroxymethyl moiety at C4 of glucopyranose moiety. The cyclic trisaccharide possesses a rarely observed perfect trigonal symmetry in the P3 space group, in a narrow cone shape, and a brick-wall type arrangement of molecules in the solid state, and exhibits a significantly enhanced binding affinity to 1-aminoadamantane in aqueous solution. PMID- 27182798 TI - Authors' Response to Cao and Hu Re: "Metabolic Syndrome and Cognitive Performance Among Chinese >= 50 Years: A Cross-Sectional Study with 3988 Participants". PMID- 27182808 TI - Pathological Diagnosis During Life in Patients With Primary Progressive Aphasia: Seeking the Holy Grail. PMID- 27182809 TI - Correction: Correction: Naturally-Acquired Immune Response against Plasmodium vivax Rhoptry-Associated Membrane Antigen. AB - [This corrects the article DOI: 10.1371/journal.pone.0148723.]. PMID- 27182810 TI - Resting state functional connectivity of the hippocampus along the anterior posterior axis and its association with glutamatergic metabolism. AB - Animal and human studies suggest differing anatomical and functional connectivity patterns of the anterior and posterior hippocampus. The biochemical underpinnings of the hippocampal resting state connectivity along this anterior-posterior axis remain unclear. We investigated twenty-five healthy male subjects in a multimodal study. We aimed to examine the relationship between resting state functional connectivity (RSFC) of the left and right hippocampus separated along the anterior-posterior axis and the corresponding glutamatergic function assessed by proton magnetic resonance spectroscopy ((1)H-MRS) of the glutamate-glutamine (Glx) complex. We observed a clear functional differentiation of the hippocampal RSFC along this axis. Moreover, a highly significant correlation was observed between the concentration of Glx in the right anterior hippocampus and its corresponding functional connectivity, but not with the amplitude of local low frequency fluctuations. Lower Glx levels were associated with a higher functional connectivity to the medial prefrontal cortex, perigenual anterior cingulate cortex (pACC) and the left ventrolateral prefrontal cortex (VLPFC). In addition, the Glx concentration in the posterior hippocampus predicted the verbal memory performance, i.e., the degree of retroactive interference. The present findings demonstrate for the first time a modulation of the anterior hippocampal RSFC by Glx concentration. PMID- 27182811 TI - Synthesis of recurrent neural networks for dynamical system simulation. AB - We review several of the most widely used techniques for training recurrent neural networks to approximate dynamical systems, then describe a novel algorithm for this task. The algorithm is based on an earlier theoretical result that guarantees the quality of the network approximation. We show that a feedforward neural network can be trained on the vector-field representation of a given dynamical system using backpropagation, then recast it as a recurrent network that replicates the original system's dynamics. After detailing this algorithm and its relation to earlier approaches, we present numerical examples that demonstrate its capabilities. One of the distinguishing features of our approach is that both the original dynamical systems and the recurrent networks that simulate them operate in continuous time. PMID- 27182812 TI - Elastic hydrogel as a sensor for detection of mechanical stress generated by single cells grown in three-dimensional environment. AB - Cell volume growth occurs in all living tissues. The growth exerts mechanical stresses on surrounding tissues that may alter tissue microenvironment, and have significant implications in health and diseases. However, the level of growth stress generated by single cells in three-dimensional (3D) environment remains to be determined. To this end, we developed a growth force microscopy technique to determine 3D distribution of the stress. The technique was based on encapsulation of cells in elastic hydrogels, and involved 3D particle tracking and mechanical analysis of gel deformation. Data from the study demonstrated that the growth stress was dynamic, and the stress distribution at the gel-cell interface was correlated inversely to the mean surface curvature or the distance to the geometric center of the cell. The stress averaged over the cell surface increased with increasing gel stiffness, suggesting that cells could alter growth stress in response to stiffness change in microenvironment. These findings suggested that the elastic hydrogel-based microscopy technique had a potential to provide new insights into mechanisms of mechanical interactions between cell and its microenvironment. PMID- 27182814 TI - Evaluation of drug penetration with cationic micelles and their penetration mechanism using an in vitro tumor model. AB - Elevated interstitial fluid pressure (IFP) and abnormal extracellular matrix (ECM) are major factors causing significant barriers to penetration of nanomedicines in solid tumors. To better understand the barriers, various in vitro tumor models including multicellular spheroids and multilayered cell cultures (MCCs) have been developing. Recently, we have established a unique in vitro tumor model composed of a MCC and an Ussing chamber system which is modified to add a hydraulic pressure gradient through the MCC. In this study, we evaluated the drug penetration ability of cationic micelles using the unique in vitro tumor model. The doxorubicin (DOX)-loaded cationic micelles, which are formed from a triblock copolymer of poly(d,l-lactide-co-glycolide)-block-branched polyethyleneimine-block-poly(d,l-lactide-co-glycolide), deeply penetrated and released the DOX throughout the MCC against convectional flow caused by a hydraulic pressure gradient. The studies using endocytosis markers and inhibitors showed that the micelles utilized mainly macropinocytosis as an internalization pathway. Furthermore, the penetration was apparently inhibited by treatment with exocytosis inhibitor Exo1. These results suggest that the active penetration of the cationic micelles is induced by iterative transcytosis via macropinocytosis and exocytosis. Our findings could be beneficial information to improve intratumoral penetration in new nanomedicines for solid tumors. PMID- 27182815 TI - The application of inelastic neutron scattering to investigate the interaction of methyl propanoate with silica. AB - A modern industrial route for the manufacture of methyl methacrylate involves the reaction of methyl propanoate and formaldehyde over a silica-supported Cs catalyst. Although the process has been successfully commercialised, little is known about the surface interactions responsible for the forward chemistry. This work concentrates upon the interaction of methyl propanoate over a representative silica. A combination of infrared spectroscopy, inelastic neutron scattering, DFT calculations, X-ray diffraction and temperature-programmed desorption is used to deduce how the ester interacts with the silica surface. PMID- 27182813 TI - Treatment of hind limb ischemia using angiogenic peptide nanofibers. AB - For a proangiogenic therapy to be successful, it must promote the development of mature vasculature for rapid reperfusion of ischemic tissue. Whole growth factor, stem cell, and gene therapies have yet to achieve the clinical success needed to become FDA-approved revascularization therapies. Herein, we characterize a biodegradable peptide-based scaffold engineered to mimic VEGF and self-assemble into a nanofibrous, thixotropic hydrogel, SLanc. We found that this injectable hydrogel was rapidly infiltrated by host cells and could be degraded while promoting the generation of neovessels. In mice with induced hind limb ischemia, this synthetic peptide scaffold promoted angiogenesis and ischemic tissue recovery, as shown by Doppler-quantified limb perfusion and a treadmill endurance test. Thirteen-month-old mice showed significant recovery within 7 days of treatment. Biodistribution studies in healthy mice showed that the hydrogel is safe when administered intramuscularly, subcutaneously, or intravenously. These preclinical studies help establish the efficacy of this treatment for peripheral artery disease due to diminished microvascular perfusion, a necessary step before clinical translation. This peptide-based approach eliminates the need for cell transplantation or viral gene transfection (therapies currently being assessed in clinical trials) and could be a more effective regenerative medicine approach to microvascular tissue engineering. PMID- 27182816 TI - Factors Associated with the Intention of Registered Dietitians to Discuss Nutrigenetics with their Patients/Clients. AB - PURPOSE: The objective of this study was to investigate factors affecting the intention of Registered Dietitians (RDs) to discuss nutrigenetics with their patients/clients. METHODS: A survey based on the theory of planned behaviour (TPB; attitude, subjective norm, and perceived behavioural control) was developed and sent by email to RD members of the Ordre professionnel des dietetistes du Quebec. Multiple regression analyses were performed to examine the determinants of intention and behaviour. RESULTS: A total of 141 RDs completed the questionnaire (5.8% response rate). On a scale from -2 to 2 (from strongly disagree to strongly agree), the intention of discussing nutrigenetics with patients/clients was neutral (mean of -0.07 +/- 0.92). The TPB construct of attitude was the most strongly associated with intention (beta = 0.66, P < 0.0001) followed by perceived behavioural control (beta = 0.33, P < 0.0001) and subjective norm (beta = 0.21, P = 0.03). Finally, 13 out of 141 RDs (~9%) actually practiced the behaviour, which was to have discussed nutrigenetics with their patients/clients in the last 3 months. Only perceived behavioural control contributed to explain the behaviour (beta = 0.17, P < 0.0001). CONCLUSIONS: Main determinants of the intention of RDs to discuss nutrigenetics with their patients/clients were determined. This knowledge will help inform the design of future educational content about nutrigenetics. PMID- 27182817 TI - Spatially segregated feedforward and feedback neurons support differential odor processing in the lateral entorhinal cortex. AB - The lateral entorhinal cortex (LEC) computes and transfers olfactory information from the olfactory bulb to the hippocampus. Here we established LEC connectivity to upstream and downstream brain regions to understand how the LEC processes olfactory information. We report that, in layer II (LII), reelin- and calbindin positive (RE(+) and CB(+)) neurons constitute two major excitatory cell types that are electrophysiologically distinct and differentially connected. RE(+) neurons convey information to the hippocampus, while CB(+) neurons project to the olfactory cortex and the olfactory bulb. In vivo calcium imaging revealed that RE(+) neurons responded with higher selectivity to specific odors than CB(+) neurons and GABAergic neurons. At the population level, odor discrimination was significantly better for RE(+) than CB(+) neurons, and was lowest for GABAergic neurons. Thus, we identified in LII of the LEC anatomically and functionally distinct neuronal subpopulations that engage differentially in feedforward and feedback signaling during odor processing. PMID- 27182818 TI - Hippocampo-cortical coupling mediates memory consolidation during sleep. AB - Memory consolidation is thought to involve a hippocampo-cortical dialog during sleep to stabilize labile memory traces for long-term storage. However, direct evidence supporting this hypothesis is lacking. We dynamically manipulated the temporal coordination between the two structures during sleep following training on a spatial memory task specifically designed to trigger encoding, but not memory consolidation. Reinforcing the endogenous coordination between hippocampal sharp wave-ripples, cortical delta waves and spindles by timed electrical stimulation resulted in a reorganization of prefrontal cortical networks, along with subsequent increased prefrontal responsivity to the task and high recall performance on the next day, contrary to control rats, which performed at chance levels. Our results provide, to the best of our knowledge, the first direct evidence for a causal role of a hippocampo-cortical dialog during sleep in memory consolidation, and indicate that the underlying mechanism involves a fine-tuned coordination between sharp wave-ripples, delta waves and spindles. PMID- 27182819 TI - Vaccination evokes gender-dependent protection against tularemia infection in C57BL/6Tac mice. AB - Francisella tularensis (Ft) is a Category A biothreat agent for which there currently is no FDA-approved vaccine. Thus, there is a substantial effort underway to develop an effective tularemia vaccine. While it is well established that gender can significantly impact susceptibility to primary infection, the impact of gender on vaccine efficacy is not well established. Thus, development of a successful vaccine against tularemia will require an understanding of the impact gender has on vaccine-induced protection against this organism. In this study, a role for gender in vaccine-induced protection following Ft challenge is identified for the first time. In the present study, mucosal vaccination with inactivated Ft (iFt) LVS elicited gender-based protection in C57BL/6Tac mice against respiratory challenge with Ft LVS. Specifically, vaccinated male mice were more susceptible to subsequent Ft LVS challenge. This increased susceptibility in male mice correlated with increased bacterial burden, increased tissue inflammation, and increased proinflammatory cytokine production late in post-challenge infection. In contrast, improved survival of iFt-vaccinated female mice correlated with reduced bacterial burden and enhanced levels of Ft-specific Abs in serum and broncho-alveolar lavage (BAL) fluid post-challenge. Furthermore, vaccination with a live attenuated vaccine consisting of an Ft LVS superoxide dismutase (SodB) mutant, which has proven efficacious against the highly virulent Ft SchuS4 strain, demonstrated similar gender bias in protection post-Ft SchuS4 challenge. Of particular significance is the fact that these are the first studies to demonstrate that gender differences impact disease outcome in the case of lethal respiratory tularemia following mucosal vaccination. In addition, these studies further emphasize the fact that gender differences must be a serious consideration in any future tularemia vaccine development studies. PMID- 27182820 TI - Vaccines against respiratory syncytial virus: The time has finally come. AB - Respiratory syncytial virus causes a significant public health burden, particularly in very young infants and the frail elderly. The legacy of enhanced RSV disease (ERD) from a whole formalin-inactivated RSV vaccine, and the complex biology of the virus and the neonate have delayed the development of effective vaccines. However, new insights into factors associated with ERD and breakthroughs in understanding the antigenic structure of the fusion (F) glycoprotein have increased optimism that vaccine development is possible. This has led to investment of time and resources by industry, regulatory authorities, governments, and nonprofit organizations to develop the infrastructure needed to make the advanced clinical development of RSV vaccine candidates a reality. PMID- 27182822 TI - Jejunal Diverticulitis. AB - BACKGROUND: Jejunal diverticulitis is a rare clinical entity often overlooked by physicians as a cause for abdominal pain. Although diagnostic capabilities improved in recent years, there is little data about diverticular disease in the proximal small bowel. The aim of this study is to present the clinical course and management in a series of eight cases of jejunal diverticulitis and possible therapeutic interventions. METHODS: A cohort retrospective analysis of all patients admitted for acute jejunal diverticulitis between January 2010 and June 2015 was conducted. Patient demographics, clinical, and surgical outcome were recorded and analyzed. RESULTS: Eight patients were admitted for acute jejunal diverticulitis with a mean age of 72.1 (range 55-87) years. Clinical presentation included six patients (75%) with a sealed perforation and only one patient demonstrated distant pneumoperitoneum. All patients were treated initially without surgery and only one patient required surgery because of diverticular complications. Recurrent episodes occurred in two patients (25%). Colonoscopy was performed in all patients after hospitalization that revealed large bowel diverticulosis in all patients (100%). Median follow-up was 8.2 months (3-15 months). CONCLUSION: Jejunal diverticulitis can be initially treated conservatively but complicated disease should be considered for surgical management. Further study is required on the relationship between small and large bowel diverticulosis. PMID- 27182821 TI - Screening for Depression in the General Population with the Center for Epidemiologic Studies Depression (CES-D): A Systematic Review with Meta-Analysis. AB - OBJECTIVE: We aimed to collect and meta-analyse the existing evidence regarding the performance of the Center for Epidemiologic Studies Depression (CES-D) for detecting depression in general population and primary care settings. METHOD: Systematic literature search in PubMed and PsychINFO. Eligible studies were: a) validation studies of screening questionnaires with information on the accuracy of the CES-D; b) samples from general populations or primary care settings; c) standardized diagnostic interviews following standard classification systems used as gold standard; and d) English or Spanish language of publication. Pooled sensitivity, specificity, likelihood ratios and diagnostic odds ratio were estimated for several cut-off points using bivariate mixed effects models for each threshold. The summary receiver operating characteristic curve was estimated with Rutter and Gatsonis mixed effects models; area under the curve was calculated. Quality of the studies was assessed with the QUADAS tool. Causes of heterogeneity were evaluated with the Rutter and Gatsonis mixed effects model including each covariate at a time. RESULTS: 28 studies (10,617 participants) met eligibility criteria. The median prevalence of Major Depression was 8.8% (IQ range from 3.8% to 12.6%). The overall area under the curve was 0.87. At the cut off 16, sensitivity was 0.87 (95% CI: 0.82-0.92), specificity 0.70 (95% CI: 0.65 0.75), and DOR 16.2 (95% CI: 10.49-25.10). Better trade-offs between sensitivity and specificity were observed (Sensitivity = 0.83, Specificity = 0.78, diagnostic odds ratio = 16.64) for cut-off 20. None of the variables assessed as possible sources of heterogeneity was found to be statistically significant. CONCLUSION: The CES-D has acceptable screening accuracy in the general population or primary care settings, but it should not be used as an isolated diagnostic measure of depression. Depending on the test objectives, the cut-off 20 may be more adequate than the value of 16, which is typically recommended. PMID- 27182823 TI - Death Pronouncements: Recommendations Based on a Survey of Bereaved Family Members. AB - PURPOSE: To clarify the family-perceived necessity of improvement in death pronouncement and explore the potential association between behaviors of physicians and the family-perceived necessity of improvement. SUBJECTS AND METHODS: A questionnaire survey was conducted involving 226 bereaved family members of patients who had died at home while receiving hospice service. A total of 91 responses were analyzed (response rate, 47%). RESULTS: All pronouncements were performed by physicians. A total of 89% (n = 81, 95% confidence interval, 81%-94%) of family members reported that they felt no necessity of improvement at all or that almost no improvement was needed. Behaviors of physicians significantly positively correlated with the family-perceived necessity of improvement were that physicians acted calmly, and were not rushed. Those negatively associated were that physicians did not verify the time of death clearly, left the patient's clothes disheveled, and touched the family members' backs or shoulders as an expression of empathy. More than 90% of family members recommended that physicians act calmly, have a suitable appearance for the situation, introduce themselves to family members, explain the cause of death explicitly, and conduct a check using a light and stethoscope for death pronouncement. CONCLUSION: Most of the family members who had experienced a patient's death at home were satisfied with the death pronouncement. Several factors were associated with family satisfaction, and further large studies are needed to confirm the results. PMID- 27182824 TI - Ubiquinol and plastoquinol triphenylphosphonium conjugates can carry electrons through phospholipid membranes. AB - Many mitochondria-targeted antioxidants (MTAs) that comprise a quinol moiety covalently attached through an aliphatic carbon chain to the lipophilic triphenylphosphonium cation are widely used for evaluating the role of mitochondria in pathological processes involving oxidative stress. The potency of MTAs to carry electrons across biological membranes and thereby mediate transmembrane redox processes was unknown. To assess this, we measured the rate of ferricyanide reduction inside liposomes by external ascorbate. Here, we show that MTAs containing ubiquinone (MitoQ series) or plastoquinone (SkQ series) can carry electrons through lipid membranes, with the rate being inversely proportional to the length of the hydrocarbon linker group. Furthermore, this process was stimulated by the hydrophobic anion tetraphenylborate suggesting that permeation of the cationic MTA through the membrane was the rate-limiting step of the process. This conclusion was supported by the observation that the rate of MTA-induced electron transfer was insensitive to nigericin, in contrast to electron transfer mediated by neutral quinone derivatives. These findings indicate that MTAs can be utilized to transfer electrons across lipid membranes and this may be applicable to the study of the electron-transport chain in mitochondria and other natural membranes exhibiting redox processes. PMID- 27182826 TI - Management Considerations for Ongoing Pregnancies Complicated by Trisomy 13 and 18. AB - Pregnancies complicated by trisomy 13 (T13) or trisomy 18 (T18) present unique challenges for obstetric management. From the initial diagnosis, the task of counseling these women and families is difficult because fetal and neonatal outcomes vary depending on the phenotype and degree of intervention chosen by the family. A literature review was performed using PubMed to gather information regarding obstetric management and outcomes of pregnancies complicated by T13 and T18. Spontaneous abortion and in uterofetal demise occur at rates well above those seen in chromosomally normal pregnancies. In addition, infants with T13 or T18 frequently have structural anomalies, which lead to worse prognoses and long term survival. In cases in which a woman and her family desire to continue the pregnancy, multidisciplinary consultation with obstetrics, social work, genetics, and pediatrics can optimize care of both the fetus and the mother. Most commonly, prenatal care does not differ from routine. A detailed delivery plan should be generated, specifically discussing interventions for the patient and her fetus. When managing pregnancies complicated by T13 and T18, active, open, and frequent communication between the patient, her family, and a multidisciplinary health care team throughout the pregnancy is crucial. PMID- 27182825 TI - Skill transfer specificity shapes perception and action under varying environmental constraints. AB - Using an ecological dynamics framework, this study investigated the generality and specificity of skill transfer processes in organisation of perception and action using climbing as a task vehicle. Fluency of hip trajectory and orientation was assessed using normalized jerk coefficients exhibited by participants as they adapted perception and action under varying environmental constraints. Twelve recreational climbers were divided into two groups: one completing a 10-m high route on an indoor climbing wall; a second undertaking a 10-m high route on an icefall in a top-rope condition. We maintained the same level of difficulty between these two performance environments. An inertial measurement unit was attached each climber's hips to collect 3D acceleration and 3D orientation data to compute jerk coefficient values. Video footage was used to record the ratio of exploratory/performatory movements. Results showed higher jerk coefficient values and number of exploratory movements for performance on the icefall route, perhaps due to greater functional complexity in perception and action required when climbing icefalls, which involves use of specific tools for anchorage. Findings demonstrated how individuals solve different motor problems, exploiting positive general transfer processes enabling participants to explore the pick-up of information for the perception of affordances specific to icefall climbing. PMID- 27182827 TI - The Effect of Paternal Age on Oocyte Donation Outcomes. AB - IMPORTANCE: In recent decades, a trend toward delayed childbearing is noted in developed countries. Whereas the effects of maternal age on fertility, pregnancy complications, and postnatal outcomes have been thoroughly explored, consequences of advanced paternal age are less well known. Oocyte donation cycles can be used as an optimal model to analyze the association between male ageing and reproductive outcomes with minimal confounding. OBJECTIVE: The purpose of this work was to summarize the updated and relevant literature dealing with the effect of paternal age on oocyte donation outcomes. RESULTS: According to the available evidence from oocyte donation cycles, it seems that no significant association exists between advanced paternal age and fertility. However, this evidence is based on few studies, many of which are of low quality, yielding conflicting results. In addition, the emerging evidence clearly indicates an increased risk of adverse postnatal manifestations of pregnancies conceived by older fathers, including de novo autosomal dominant disorders, impaired neurocognitive development, and increased risk of malignancy. CONCLUSIONS AND RELEVANCE: This review may be of aid to medical practitioners in counseling couples on the risks of delayed childbearing. PMID- 27182828 TI - Role of Metformin in Women's Health: Review of Its Current Place in Clinical Practice and Emerging Indications for Future. AB - IMPORTANCE: Metformin, an oral antihyperglycemic drug, acts as an insulin sensitizer in the treatment of type 2 diabetes mellitus. It has also been widely used in the treatment of polycystic ovary syndrome (PCOS) and gestational diabetes mellitus. Although randomized clinical trials have failed to establish its superiority over other forms of treatment, metformin continues to be a treatment option in specific subgroups of women either alone or as an adjunct with other therapies in management of PCOS. OBJECTIVE AND EVIDENCE ACQUISITION: This narrative review was conducted to assess the present role of metformin in management of clinical conditions related to women's health. A PubMed search was conducted using the following terms: "metformin," "polycystic," "ovary," "Women's," "health," "gestational," "diabetes," "cancer," and "fertility," and all relevant studies were evaluated for accumulation of evidence. RESULTS AND CONCLUSIONS: Metformin is used as a second-line drug for ovulation induction in women with PCOS who are resistant to clomiphene citrate. Metformin also forms one of the management options in women who need antiandrogen therapy without the need for contraception at the same time. Women with PCOS undergoing in vitro fertilization are likely to benefit from metformin therapy to reduce their risk of ovarian hyperstimulation syndrome. Metformin alone or in combination with insulin has been reported to have similar safety and efficacy to insulin for the treatment of GDM. There is growing evidence that metformin may be associated with a decreased risk of developing cancers and improved response to chemotherapy. PMID- 27182829 TI - Near-Edge X-ray Absorption Fine Structure within Multilevel Coupled Cluster Theory. AB - Core excited states are challenging to calculate, mainly because they are embedded in a manifold of high-energy valence-excited states. However, their locality makes their determination ideal for local correlation methods. In this paper, we demonstrate the performance of multilevel coupled cluster theory in computing core spectra both within the core-valence separated and the asymmetric Lanczos implementations of coupled cluster linear response theory. We also propose a visualization tool to analyze the excitations using the difference between the ground-state and excited-state electron densities. PMID- 27182830 TI - PIZZARO: Forensic analysis and restoration of image and video data. AB - This paper introduces a set of methods for image and video forensic analysis. They were designed to help to assess image and video credibility and origin and to restore and increase image quality by diminishing unwanted blur, noise, and other possible artifacts. The motivation came from the best practices used in the criminal investigation utilizing images and/or videos. The determination of the image source, the verification of the image content, and image restoration were identified as the most important issues of which automation can facilitate criminalists work. Novel theoretical results complemented with existing approaches (LCD re-capture detection and denoising) were implemented in the PIZZARO software tool, which consists of the image processing functionality as well as of reporting and archiving functions to ensure the repeatability of image analysis procedures and thus fulfills formal aspects of the image/video analysis work. Comparison of new proposed methods with the state of the art approaches is shown. Real use cases are presented, which illustrate the functionality of the developed methods and demonstrate their applicability in different situations. The use cases as well as the method design were solved in tight cooperation of scientists from the Institute of Criminalistics, National Drug Headquarters of the Criminal Police and Investigation Service of the Police of the Czech Republic, and image processing experts from the Czech Academy of Sciences. PMID- 27182831 TI - Influence of the treatment facility volume on the survival of patients with non Hodgkin lymphoma. AB - BACKGROUND: Prior studies have shown that a higher hospital volume or physician caseload is associated with better outcomes for complex and uncommon surgical procedures. Similar studies in the medical management of rare diseases such as hematologic cancers are limited. This retrospective, observational study using the US National Cancer Data Base determined the extent to which the number of new non-Hodgkin lymphoma (NHL) patients treated annually at a treatment facility affected overall survival (OS). METHODS: There were 278,985 patients treated at 1151 facilities from 1998 to 2006. Treatment facilities were classified by quartiles based on the average number of new NHL patients seen annually: quartile 1 (Q1), 2 to 13 patients; quartile 2 (Q2), 14 to 20 patients; quartile 3 (Q3), 21 to 32 patients; and quartile 4 (Q4), 33 or more patients. The outcome of interest was OS according to facility volume. RESULTS: The unadjusted median OS was 61.8 months for Q1, 65.9 months for Q2, 71.4 months for Q3, and 83.6 months for Q4. A multivariate analysis that was adjusted for demographic (sex, age, race, and ethnicity), socioeconomic (income and insurance type), geographic (area of residence), disease-specific (NHL subtype and stage), and facility-specific factors (type and location) showed that the facility volume was associated with OS. Compared with patients at Q4 facilities, patients at lower quartile facilities had higher mortality (hazard ratio for Q3, 1.05 [95% confidence interval, 1.04-1.06]; hazard ratio for Q2, 1.08 [95% confidence interval, 1.07 1.10]; hazard ratio for Q1, 1.14 [95% confidence interval, 1.11-1.17]). CONCLUSIONS: NHL patients treated at higher volume facilities may survive longer than those treated at lower volume facilities. Further work is needed to understand the mechanisms of these differences and whether volume should be considered in the determination of referrals for NHL patients. Cancer 2016;122:2552-9. (c) 2016 American Cancer Society. PMID- 27182832 TI - Evaluation and optimization of occupational eye lens dosimetry during positron emission tomography (PET) procedures. AB - The last recommendations of the International Commission on Radiological Protection for eye lens dose suggest an important reduction on the radiation limits associated with early and late tissue reactions. The aim of this work is to quantify and optimize the eye lens dose associated to nurse staff during positron emission tomography (PET) procedures. PET is one of the most important diagnostic methods of oncological and neurological cancer disease involving an important number of workers exposed to the high energy isotope F-18. We characterize the relevant stages as preparation and administration of monodose syringes in terms of occupational dose. A direct reading silicon dosimeter was used to measure the lens dose to staff. The highest dose of radiation was observed during preparation of the fluorodesoxyglucose (FDG) syringes. By optimizing a suitable vials' distribution of FDG we find an important reduction in occupational doses. Extrapolation of our data to other clinical scenarios indicates that, depending on the work load and/or syringes activity, safety limits of the dose might be exceeded. PMID- 27182833 TI - Improving Loop Modeling of the Antibody Complementarity-Determining Region 3 Using Knowledge-Based Restraints. AB - Structural restrictions are present even in the most sequence diverse portions of antibodies, the complementary determining region (CDR) loops. Previous studies identified robust rules that define canonical structures for five of the six CDR loops, however the heavy chain CDR 3 (HCDR3) defies standard classification attempts. The HCDR3 loop can be subdivided into two domains referred to as the "torso" and the "head" domains and two major families of canonical torso structures have been identified; the more prevalent "bulged" and less frequent "non-bulged" torsos. In the present study, we found that Rosetta loop modeling of 28 benchmark bulged HCDR3 loops is improved with knowledge-based structural restraints developed from available antibody crystal structures in the PDB. These restraints restrict the sampling space Rosetta searches in the torso domain, limiting the phi and psi angles of these residues to conformations that have been experimentally observed. The application of these restraints in Rosetta result in more native-like structure sampling and improved score-based differentiation of native-like HCDR3 models, significantly improving our ability to model antibody HCDR3 loops. PMID- 27182835 TI - The impact of a tax on sugar-sweetened beverages according to socio-economic position: a systematic review of the evidence. AB - OBJECTIVE: A tax on sugar-sweetened beverages (SSB) has been proposed to address population weight gain but the effect across socio-economic position (SEP) is unclear. The current study aimed to clarify the differential impact(s) of SSB taxes on beverage purchases and consumption, weight outcomes and the amount paid in SSB taxes according to SEP. DESIGN: Databases (OVID and EMBASE) and grey literature were systematically searched in June 2015 to identify studies that examined effects of an SSB price increase on beverage purchases or consumption, weight outcomes or the amount paid in tax across SEP, within high-income countries. RESULTS: Of the eleven included articles, three study types were identified: (i) those that examined the association between variation in SSB taxes and SSB consumption and/or body weight (n 3); (ii) price elasticity estimation of SSB demand (n 1); and (iii) modelling of hypothetical SSB taxes by combining price elasticity estimates with population SEP-specific beverage consumption, energy intake or body weight (n 7). Few studies statistically tested differences in outcomes between SEP groups. Nevertheless, of the seven studies that reported on changes in weight outcomes for the total population following an increase in SSB price, all reported either similar reductions in weight across SEP groups or greater reductions for lower compared with higher SEP groups. All studies that examined the average household amount paid in tax (n 5) reported that an SSB tax would be regressive, but with small differences between higher- and lower-income households (0.10-1.0 % and 0.03 %-0.60 % of annual household income paid in SSB tax for low- and high-income households, respectively). CONCLUSIONS: Based on the available evidence, a tax on SSB will deliver similar population weight benefits across socio-economic strata or greater benefits for lower SEP groups. An SSB tax is shown to be consistently financially regressive, but to a small degree. PMID- 27182834 TI - The Presence and Anti-HIV-1 Function of Tenascin C in Breast Milk and Genital Fluids. AB - Tenascin-C (TNC) is a newly identified innate HIV-1-neutralizing protein present in breast milk, yet its presence and potential HIV-inhibitory function in other mucosal fluids is unknown. In this study, we identified TNC as a component of semen and cervical fluid of HIV-1-infected and uninfected individuals, although it is present at a significantly lower concentration and frequency compared to that of colostrum and mature breast milk, potentially due to genital fluid protease degradation. However, TNC was able to neutralize HIV-1 after exposure to low pH, suggesting that TNC could be active at low pH in the vaginal compartment. As mucosal fluids are complex and contain a number of proteins known to interact with the HIV-1 envelope, we further studied the relationship between the concentration of TNC and neutralizing activity in breast milk. The amount of TNC correlated only weakly with the overall innate HIV-1-neutralizing activity of breast milk of uninfected women and negatively correlated with neutralizing activity in milk of HIV-1 infected women, indicating that the amount of TNC in mucosal fluids is not adequate to impede HIV-1 transmission. Moreover, the presence of polyclonal IgG from milk of HIV-1 infected women, but not other HIV-1 envelope-binding milk proteins or monoclonal antibodies, blocked the neutralizing activity of TNC. Finally, as exogenous administration of TNC would be necessary for it to mediate measurable HIV-1 neutralizing activity in mucosal compartments, we established that recombinantly produced TNC has neutralizing activity against transmitted/founder HIV-1 strains that mimic that of purified TNC. Thus, we conclude that endogenous TNC concentration in mucosal fluids is likely inadequate to block HIV-1 transmission to uninfected individuals. PMID- 27182837 TI - Preliminary Results of Magnetically Controlled Growing Rods for Early Onset Scoliosis. AB - BACKGROUND: Growth-sparing techniques for the treatment of early onset scoliosis (EOS) have developed significantly over the last years. Traditional growing rods (GRs) require repeated surgical lengthening under anesthesia. Since June 2011 we have been using the magnetically controlled growing rods (MCGR) to treat patients with progressive EOS. METHODS: Thirty-five patients with EOS of different etiologies underwent treatment with MCGR. We record about our preliminary results of 24 patients who fulfilled the inclusion criteria of a minimum follow-up (FU) of 12 month and >3 lengthenings. The mean age at surgery was 8.9+/-2.5 years. Correction of the primary curve after the index surgery and after lengthenings was measured on standing radiographs using the Cobb technique. T1-T12 and T1-S1 spinal length were also measured. Intraoperative and postoperative complications were recorded. RESULTS: The mean FU was 21.1+/-7.3 months. All patients had a minimum of 3 outpatient lengthenings [mean, 4.6+/-1.5 (range, 3 to 8)]. The mean primary curve was 63+/-15 degrees (range, 40 to 96 degrees) and improved to 29+/ 11 degrees (range, 11 to 53 degrees; P<0.001) after MCGR. The mean major curve after most recent lengthening was 26 degrees (range, 8 to 60 degrees; P<0.07). The T1-T12 as well as the T1-S1 length increased significantly (P<0.001). The mean preoperative thoracic kyphosis decreased from 43+/-24 degrees (range, -32 to 86 degrees) to 27+/-12 degrees (range, 9 to 50 degrees; P<0.001) after surgery, respectively, and measured 32+/-12 degrees (range, 12 to 64 degrees; P<0.05) at last FU. In 1 patient a loss of distraction occurred making rod exchange necessary. Three patients developed a proximal junctional kyphosis and in another patient a screw pull out occurred that required revision surgery. CONCLUSIONS: Our results demonstrate that MCGR is a safe and effective nonfusion technique in the treatment of progressive EOS avoiding repeated surgical lengthening procedures. It provides adequate distraction similar to standard GR. The magnetically induced transcutaneous lengthening allows noninvasive distraction achieving spinal growth comparable to conventional GR techniques. LEVEL OF EVIDENCE: Level IV-retrospective nonrandomized objective study. PMID- 27182836 TI - Feasibility of a Supportive Other Intervention for Opiate-Dependent Patients Entering Inpatient Detoxification. AB - Involvement of supportive others (SOs; defined as patient's most important person) in substance use treatment is widely accepted as a valuable addition, but is not routinely implemented during inpatient detoxification for opioid use disorders. The current study explores the feasibility of a brief SO intervention for individuals detoxing from opioids. Data regarding ability to identify an SO, the nature of the SO relationship, and willingness to invite an SO to help with long-term abstinence were collected from 369 patients attending inpatient opioid detoxification. For those unwilling to participate in an SO intervention, possible barriers to participation were examined. Results indicated that the majority (71.8%) of patients were willing to involve SOs, and that they believed that their SO was supportive of their treatment (88.1%). Those unwilling to invite an SO reported that their identified SO was a young child or that they wanted to make life changes independently. We conclude that SO involvement in substance use treatment at the time of opioid detoxification is feasible and could be engaged in future interventions. PMID- 27182839 TI - Design and application of 3D-printed stepless beam modulators in proton therapy. AB - A new method for the design of stepless beam modulators for proton therapy is described and verified. Simulations of the classic designs are compared against the stepless method for various modulation widths which are clinically applicable in proton eye therapy. Three modulator wheels were printed using a Stratasys Objet30 3D printer. The resulting depth dose distributions showed improved uniformity over the classic stepped designs. Simulated results imply a possible improvement in distal penumbra width; however, more accurate measurements are needed to fully verify this effect. Lastly, simulations were done to model bio equivalence to Co-60 cell kill. A wheel was successfully designed to flatten this metric. PMID- 27182838 TI - CTX-M-15-Type Extended-Spectrum Beta-Lactamase-Producing Escherichia coli as Causative Agent of Bovine Mastitis. AB - In the present study, 3 quarter milk samples from 3 cows showing clinical signs of mastitis were investigated. Three Escherichia coli were isolated and were found resistant to ceftiofur and cefquinome. The isolates were detected as extended-spectrum beta-lactamase (ESBL) producers by the Clinical and Laboratory Standards Institute (CLSI) ESBL screening test and combined disc method. CTX-M- and TEM-type beta-lactamase genes (blaCTX-M blaTEM) were detected by polymerase chain reaction in the isolates. Sequencing of blaCTX-M and blaTEM genes showed that the isolates were both TEM-1- and CTX-M-15-type beta-lactamase producers. The isolates were tested by agar disc diffusion test for susceptibility to various classes of antibiotics (aminoglycosides, quinolones, phenicols, folate pathway inhibitors, and tetracyclines), and they were determined as multidrug resistant. Therefore, this is the first report indicating the involvement of multidrug-resistant CTX-M-15-type ESBL-producing E. coli as a cause of bovine mastitis in Turkey. PMID- 27182840 TI - Emerging Hyperkalemia Following Valproic Acid Use in an Elderly Patient With Late Onset Mania. PMID- 27182842 TI - "Calculating The Toll Of Trauma" in the headlines: Portrayals of posttraumatic stress disorder in the New York Times (1980-2015). AB - Public awareness about traumatic stress is needed to address trauma as a public health issue. News media influence public awareness, but little is known about how traumatic-related disorders are portrayed in the news. A content analysis was conducted of all articles that mentioned posttraumatic stress disorder (PTSD) in The New York Times between 1980-2015. There were 871 articles analyzed. The number of PTSD articles published annually increased dramatically, from 2 in 1980 to 70 in 2014. Overall, 50.6% of articles were focused on military populations. Combat was identified as the trauma exposure in 38.0% of articles, while sexual assault was identified in 8.7%. Negative themes such as crimes perpetrated by people with possible PTSD (18.0%) and substance abuse (11.5%) were prominent, substance abuse being more prevalent in articles focused on military populations (16.4% vs. 6.3%, p = <.001). Only 9.1% of articles mentioned PTSD treatment options and this theme became less prevalent over time-ranging from 19.4% of articles published between 1980-1995 to just 5.7% of articles published between 2005-2015 (p = <.001). Results suggest that public awareness of PTSD has increased, but may be incomplete, inaccurate, and perpetuate PTSD stigma at individual- and institutional-levels. These findings can inform advocacy strategies that enhance public awareness about PTSD and traumatic stress. (PsycINFO Database Record PMID- 27182843 TI - Influence of Divalent Cations on Deformation and Rupture of Adsorbed Lipid Vesicles. AB - The fate of adsorbed lipid vesicles on solid supports depends on numerous experimental parameters and typically results in the formation of a supported lipid bilayer (SLB) or an adsorbed vesicle layer. One of the poorly understood questions relates to how divalent cations appear to promote SLB formation in some cases. The complexity arises from the multiple ways in which divalent cations affect vesicle-substrate and vesicle-vesicle interactions as well as vesicle properties. These interactions are reflected, e.g., in the degree of deformation of adsorbed vesicles (if they do not rupture). It is, however, experimentally challenging to measure the extent of vesicle deformation in real-time. Herein, we investigated the effect of divalent cations (Mg(2+), Ca(2+), Sr(2+)) on the adsorption of zwitterionic 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) lipid vesicles onto silicon oxide- and titanium oxide-coated substrates. The vesicle adsorption process was tracked using the quartz crystal microbalance-dissipation (QCM-D) and localized surface plasmon resonance (LSPR) measurement techniques. On silicon oxide, vesicle adsorption led to SLB formation in all cases, while vesicles adsorbed but did not rupture on titanium oxide. It was identified that divalent cations promote increased deformation of adsorbed vesicles on both substrates and enhanced rupture on silicon oxide in the order Ca(2+) > Mg(2+) > Sr(2+). The influence of divalent cations on different factors in these systems is discussed, clarifying experimental observations on both substrates. Taken together, the findings in this work offer insight into how divalent cations modulate the interfacial science of supported membrane systems. PMID- 27182841 TI - Metabolic drift in the aging brain. AB - Brain function is highly dependent upon controlled energy metabolism whose loss heralds cognitive impairments. This is particularly notable in the aged individuals and in age-related neurodegenerative diseases. However, how metabolic homeostasis is disrupted in the aging brain is still poorly understood. Here we performed global, metabolomic and proteomic analyses across different anatomical regions of mouse brain at different stages of its adult lifespan. Interestingly, while severe proteomic imbalance was absent, global-untargeted metabolomics revealed an energymetabolic drift or significant imbalance in core metabolite levels in aged mouse brains. Metabolic imbalance was characterized by compromised cellular energy status (NAD decline, increased AMP/ATP, purine/pyrimidine accumulation) and significantly altered oxidative phosphorylation and nucleotide biosynthesis and degradation. The central energy metabolic drift suggests a failure of the cellular machinery to restore metabostasis (metabolite homeostasis) in the aged brain and therefore an inability to respond properly to external stimuli, likely driving the alterations in signaling activity and thus in neuronal function and communication. PMID- 27182844 TI - Performance on the Defense Automated Neurobehavioral Assessment across controlled environmental conditions. AB - Neurocognitive assessment tools (NCAT) are commonly used to screen for changes in cognitive functioning following a mild traumatic brain injury and to assist with a return to duty decision. As such, it is critical to determine if performance on the Defense Automated Neurobehavioral Assessment (DANA) is adversely affected by operationally-relevant field environments. Differences in DANA performance between a thermoneutral environment and three simulated operationally-relevant field environments across the thermal stress continuum were calculated for 16 healthy U.S. Navy service members. Practice effects associated with brief test retest intervals were calculated within each environmental condition. There were no significant differences between the simulated environmental conditions suggesting that performance on the DANA Brief is not impacted by thermal stress. Additionally, there were no significant differences in performance within each simulated environmental condition associated with repeated administrations. PMID- 27182845 TI - Primary Renal Rhabdomyosarcoma: An Unusual Bone Metastasizing Tumor of Kidney. AB - Rhabdomyosarcoma (RMS) is one of the common malignant tumors in the pediatric age group. There is only a single case report of primary renal alveolar RMS. Fine needle aspiration (FNA) findings of primary renal RMS has not been reported so far. Hence we present an unusual case of primary alveolar RMS of the kidney. An 11 year old boy presented with an abdominal mass. On FNA a diagnosis of undifferentiated sarcoma and anaplastic Wilms tumor were considered. The tumor was resected and showed histopathological features of alveolar rhabdomyosarcoma. He developed multiple bony metastases and succumbed to the illness despite aggressive chemotherapy. RMS of the kidney should be considered in the differential diagnosis of children with a renal mass, and may have an aggressive clinical course with bone metastases. PMID- 27182846 TI - Metabolic evolution and (13) C flux analysis of a succinate dehydrogenase deficient strain of Yarrowia lipolytica. AB - Bio-based succinic acid production can redirect industrial chemistry processes from using limited hydrocarbons to renewable carbohydrates. A fermentation process that does not require pH-titrating agents will be advantageous to the industry. Previously, a Yarrowia lipolytica strain that was defective for succinate dehydrogenase was constructed and was found to accumulate up to 17.5 g L(-1) of succinic acid when grown on glycerol without buffering. Here, a derivative mutant was isolated that produced 40.5 g L(-1) of succinic acid in 36 h with a yield of 0.32 g g(-1) glycerol. A combination approach of induced mutagenesis and metabolic evolution allowed isolation of another derivative that could utilize glucose efficiently and accumulated 50.2 g L(-1) succinic acid in 54 h with a yield of 0.43 g g(-1) . The parent strain of these isolated mutants was used for [1,6-(13) C2 ]glucose assimilation analysis. At least 35% glucose was estimated to be utilized through the pentose phosphate pathway, while >=84% succinic acid was formed through the oxidative branch of the tricarboxylic acid cycle. Biotechnol. Bioeng. 2016;113: 2425-2432. (c) 2016 Wiley Periodicals, Inc. PMID- 27182847 TI - The effectiveness of a self-management occupational therapy intervention on activity performance in individuals with multiple sclerosis-related fatigue: a randomized-controlled trial. AB - Purpose to evaluate the effectiveness of an individual self-management occupational therapy intervention program (SMOoTh) versus relaxation on the performance of and satisfaction with relevant daily activities in individuals with multiple sclerosis (MS)-related fatigue. in a single-blind randomized controlled trial, 31 patients with MS (SMOoTh: n=17, relaxation: n=14) were randomly allocated to three individual sessions focusing on pacing, prioritizing, ergonomics, and self-management (SMOoTh) or on stress management and relaxation (relaxation). Outcomes (blind assessor): Canadian Occupational Performance Measure (COPM) (primary), Modified Fatigue Impact Scale, Checklist Individual Strength and Short-Form Health Measure. COPM improved in the SMOoTh and relaxation group after the intervention and 3 months later (COPM performance: F=13.1, P=0.001 and COPM satisfaction: F=10.4, P=0.001); nonsignificant group differences showed a trend in favor of SMOoTh. Modified Fatigue Impact Scale, Checklist Individual Strength, and most of the Short-Form Health Measure subscales did not change. Clinically relevant changes in COPM performance scores were found in 71 and 27% of patients in the SMOoTh versus the relaxation group. Both interventions seem to be feasible approaches to improve performance of and satisfaction with relevant daily activities in people with MS, with a sustained effect after 3 months. Neither program altered change fatigue (impact) or quality of life. Future studies with larger sample sizes are needed. PMID- 27182848 TI - Society of Critical Care Medicine Presidential Address-45th Annual Congress, February 2016, Orlando, Florida. PMID- 27182849 TI - Guidelines for the Appropriate Use of Bedside General and Cardiac Ultrasonography in the Evaluation of Critically Ill Patients-Part II: Cardiac Ultrasonography. AB - OBJECTIVE: To establish evidence-based guidelines for the use of bedside cardiac ultrasound, echocardiography, in the ICU and equivalent care sites. METHODS: Grading of Recommendations, Assessment, Development and Evaluation system was used to rank the "levels" of quality of evidence into high (A), moderate (B), or low (C) and to determine the "strength" of recommendations as either strong (strength class 1) or conditional/weak (strength class 2), thus generating six "grades" of recommendations (1A-1B-1C-2A-2B-2C). Grading of Recommendations, Assessment, Development and Evaluation was used for all questions with clinically relevant outcomes. RAND Appropriateness Method, incorporating the modified Delphi technique, was used in formulating recommendations related to terminology or definitions or in those based purely on expert consensus. The process was conducted by teleconference and electronic-based discussion, following clear rules for establishing consensus and agreement/disagreement. Individual panel members provided full disclosure and were judged to be free of any commercial bias. RESULTS: Forty-five statements were considered. Among these statements, six did not achieve agreement based on RAND appropriateness method rules (majority of at least 70%). Fifteen statements were approved as conditional recommendations (strength class 2). The rest (24 statements) were approved as strong recommendations (strength class 1). Each recommendation was also linked to its level of quality of evidence and the required level of echo expertise of the intensivist. Key recommendations, listed by category, included the use of cardiac ultrasonography to assess preload responsiveness in mechanically ventilated (1B) patients, left ventricular (LV) systolic (1C) and diastolic (2C) function, acute cor pulmonale (ACP) (1C), pulmonary hypertension (1B), symptomatic pulmonary embolism (PE) (1C), right ventricular (RV) infarct (1C), the efficacy of fluid resuscitation (1C) and inotropic therapy (2C), presence of RV dysfunction (2C) in septic shock, the reason for cardiac arrest to assist in cardiopulmonary resuscitation (1B-2C depending on rhythm), status in acute coronary syndromes (ACS) (1C), the presence of pericardial effusion (1C), cardiac tamponade (1B), valvular dysfunction (1C), endocarditis in native (2C) or mechanical valves (1B), great vessel disease and injury (2C), penetrating chest trauma (1C) and for use of contrast (1B-2C depending on indication). Finally, several recommendations were made regarding the use of bedside cardiac ultrasound in pediatric patients ranging from 1B for preload responsiveness to no recommendation for RV dysfunction. CONCLUSIONS: There was strong agreement among a large cohort of international experts regarding several class 1 recommendations for the use of bedside cardiac ultrasound, echocardiography, in the ICU. Evidence-based recommendations regarding the appropriate use of this technology are a step toward improving patient outcomes in relevant patients and guiding appropriate integration of ultrasound into critical care practice. PMID- 27182850 TI - "Vitamin S" (Steroids) and Vitamin C for the Treatment of Severe Sepsis and Septic Shock! PMID- 27182851 TI - Measuring Clinical Performance: Make Sure the Ruler Is Accurate. PMID- 27182852 TI - Impact of Alteration of Iron Homeostasis in ICU Patients. PMID- 27182853 TI - Outcomes Following Sepsis and Cardiopulmonary Resuscitation: Fare Thee Well or Worse for Wear? PMID- 27182854 TI - I Miss the Sound of Your Voice: Earlier Speech in Tracheostomy Patients. PMID- 27182855 TI - Blood, Sweat, and teARDS. PMID- 27182856 TI - Looking for the Grail, Finding Traces on the Way. PMID- 27182857 TI - Survival Without Transfusion Is Possible but Not Recommended for All. PMID- 27182858 TI - Early Mobilization in the ICU: Help or Hype? PMID- 27182859 TI - Reducing the Angst Associated With Withdrawal of Life-Sustaining Therapy. PMID- 27182860 TI - Neurocognitive Deficits in Adolescent Survivors of Neonatal Extracorporeal Membrane Oxygenation: The Evidence Unfolds. PMID- 27182861 TI - Pharmacologic Therapies for ICU-Acquired Weakness: A Long Road Ahead. PMID- 27182862 TI - Corticosteroids for Influenza Pneumonia: Hold Off for Now! PMID- 27182863 TI - Learning Critical Care Echocardiography: The Start of an Evidence-Based Approach? PMID- 27182865 TI - Technology is Great, Except When It Isn't! PMID- 27182864 TI - Predicting Large Vessel Occlusion in Acute Ischemic Stroke: Less is More. PMID- 27182866 TI - Better Measures, Better Trials, Better Outcomes in Survivors of Critical Illness. PMID- 27182867 TI - Selenium and Niacin for Sepsis Therapy: The Sum Is Greater Than Its Parts. PMID- 27182868 TI - Is Helium Eclipsing Current Thromboembolic Stroke Therapy? PMID- 27182869 TI - Something Old, Something New...Something Else to Consider in Blood Utilization. PMID- 27182870 TI - Treating Sepsis: Nearest Neighbors and Predicting Beginnings. PMID- 27182871 TI - Sepsis-The Final Common Pathway to Death From Multiple Organ Failure in Infection. PMID- 27182872 TI - The authors reply. PMID- 27182873 TI - Misclassification of Acute Kidney Injury and Its Impact on Hospital Survival. PMID- 27182874 TI - The authors reply. PMID- 27182875 TI - Three Cases of Severe Pulmonary Embolism After Dual-Lumen Extracorporeal Membrane Oxygenation Catheter Removal. PMID- 27182876 TI - The authors reply. PMID- 27182877 TI - The Richmond Agitation-Sedation Scale Should Not Be Used to Evaluate Neurologic Function. PMID- 27182878 TI - The authors reply. PMID- 27182879 TI - The Barriers and Enablers to Single-Specialty Status in Critical Care. PMID- 27182880 TI - The author replies. PMID- 27182881 TI - Trials and Tribulations of Therapies for the Acute Respiratory Distress Syndrome. PMID- 27182882 TI - The authors reply. PMID- 27182883 TI - Risk Stratification of Infected Patients in Emergency Department. PMID- 27182884 TI - Magnetic Driving Flowerlike Soft Platform: Biomimetic Fabrication and External Regulation. AB - Nature-inspired actuators that can be driven by various stimuli are an emerging application in mobile microrobotics and microfluidics. In this study, a soft and multiple-environment-adaptive robotic platform with ferromagnetic particles impregnated in silicon-based polymer is adopted to fabricate microrobots for minimally invasive locomotion and control interaction with their environment. As an intelligent structure of platform, the change of its bending, deformation, and flapping displacement is rapid, reversible, and continuously controllable with sweeping and multicycle magnetic actuation. The bending angle of the soft platform (0.2 mm in thickness and 8.5 mm in length) can be deflected up to almost 90 degrees within 2.7 s. Experiments demonstrated that the flexible platform of human skin-like material in various shapes, that is, flowerlike shapes, can transport a cargo to targeted area in air and a variety of liquids. It indicates excellent magnetic-actuation ability and good controllability. The results may be helpful in developing a magnetic-driven carrying platform, which can be operated like a human finger to manipulate biological objects such as single cells, microbeads, or embryos. Especially, it is likely to be used in harsh chemical and physical circumstances. PMID- 27182885 TI - Genomic African and Native American Ancestry and Chagas Disease: The Bambui (Brazil) Epigen Cohort Study of Aging. AB - BACKGROUND: The influence of genetic ancestry on Trypanosoma cruzi infection and Chagas disease outcomes is unknown. METHODOLOGY/PRINCIPAL FINDINGS: We used 370,539 Single Nucleotide Polymorphisms (SNPs) to examine the association between individual proportions of African, European and Native American genomic ancestry with T. cruzi infection and related outcomes in 1,341 participants (aged >= 60 years) of the Bambui (Brazil) population-based cohort study of aging. Potential confounding variables included sociodemographic characteristics and an array of health measures. The prevalence of T. cruzi infection was 37.5% and 56.3% of those infected had a major ECG abnormality. Baseline T. cruzi infection was correlated with higher levels of African and Native American ancestry, which in turn were strongly associated with poor socioeconomic circumstances. Cardiomyopathy in infected persons was not significantly associated with African or Native American ancestry levels. Infected persons with a major ECG abnormality were at increased risk of 15-year mortality relative to their counterparts with no such abnormalities (adjusted hazard ratio = 1.80; 95% 1.41, 2.32). African and Native American ancestry levels had no significant effect modifying this association. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that African and Native American ancestry have no influence on the presence of major ECG abnormalities and had no influence on the ability of an ECG abnormality to predict mortality in older people infected with T. cruzi. In contrast, our results revealed a strong and independent association between prevalent T. cruzi infection and higher levels of African and Native American ancestry. Whether this association is a consequence of genetic background or differential exposure to infection remains to be determined. PMID- 27182886 TI - Effects of Arachidonic Acid Supplementation on Acute Anabolic Signaling and Chronic Functional Performance and Body Composition Adaptations. AB - BACKGROUND: The primary purpose of this investigation was to examine the effects of arachidonic acid (ARA) supplementation on functional performance and body composition in trained males. In addition, we performed a secondary study looking at molecular responses of ARA supplementation following an acute exercise bout in rodents. METHODS: Thirty strength-trained males (age: 20.4 +/- 2.1 yrs) were randomly divided into two groups: ARA or placebo (i.e. CTL). Then, both groups underwent an 8-week, 3-day per week, non-periodized training protocol. Quadriceps muscle thickness, whole-body composition scan (DEXA), muscle strength, and power were assessed at baseline and post-test. In the rodent model, male Wistar rats (~250 g, ~8 weeks old) were pre-fed with either ARA or water (CTL) for 8 days and were fed the final dose of ARA prior to being acutely strength trained via electrical stimulation on unilateral plantar flexions. A mixed muscle sample was removed from the exercised and non-exercised leg 3 hours post-exercise. RESULTS: Lean body mass (2.9%, p<0.0005), upper-body strength (8.7%, p<0.0001), and peak power (12.7%, p<0.0001) increased only in the ARA group. For the animal trial, GSK-beta (Ser9) phosphorylation (p<0.001) independent of exercise and AMPK phosphorylation after exercise (p-AMPK less in ARA, p = 0.041) were different in ARA-fed versus CTL rats. CONCLUSIONS: Our findings suggest that ARA supplementation can positively augment strength-training induced adaptations in resistance-trained males. However, chronic studies at the molecular level are required to further elucidate how ARA combined with strength training affect muscle adaptation. PMID- 27182888 TI - Correction: Long-Term Low Carbohydrate Diet Leads to Deleterious Metabolic Manifestations in Diabetic Mice. AB - [This corrects the article DOI: 10.1371/journal.pone.0104948.]. PMID- 27182887 TI - First Description of Hepacivirus and Pegivirus Infection in Domestic Horses in China: A Study in Guangdong Province, Heilongjiang Province and Hong Kong District. AB - Since 2012, three viruses, known as equine hepacivirus (EqHV), equine pegivirus (EPgV) and Theiler's disease-associated virus (TDAV), have been discovered in equines. Given that these viruses are the newest members of the Flaviviridae family, genomic information concerning circulating EqHV, EPgV and TDAV strains around the world is limited. To date, no genetic surveillance studies have been performed on these three viruses in the equine population of China. Here, a total of 177 serum samples were collected from equines across China between 2014 and 2015. Using PCR, we detected viral RNA in the serum samples, six of which were EqHV positive and two of which were EPgV positive. Co-infection with the two viruses was not observed among the Chinese equines studied, and TDAV RNA was not detected in the equine serum samples collected for this study. Phylogenetic analysis of partial NS5B open reading frame (ORF), NS3 ORF, and 5' untranslated region nucleotide sequences from EqHV as well as partial NS3 ORF sequence from EPgV indicated that EqHV and EPgV have evolved into two main clades by themselves, both of which are circulating in China. Based on the partial NS5B and NS3 ORF sequences of EqHV, the sequences of one clade were also split into two subclades. This study enriches our knowledge of the geographic distribution of these three equine viruses. PMID- 27182889 TI - "Even if I Don't Remember, I Feel Better". A Qualitative Study of Patients with Early-Stage Non-Small Cell Lung Cancer Undergoing Stereotactic Body Radiotherapy or Surgery. AB - RATIONALE: While surgical resection is recommended for most patients with early stage lung cancer according to the National Comprehensive Cancer Network guidelines, stereotactic body radiotherapy is increasingly being used. Provider patient communication regarding the risks and benefits of each approach may be a modifiable factor leading to improved patient-centered outcomes. OBJECTIVES: To qualitatively describe the experiences of patients undergoing either surgery or stereotactic body radiotherapy for early stage non-small cell lung cancer. METHODS: We qualitatively evaluated and used content analysis to describe the experiences of 13 patients with early clinical stage non-small cell lung cancer before undergoing treatment in three health care systems in the Pacific Northwest, with a focus on knowledge obtained, communication, and feelings of distress. MEASUREMENTS AND MAIN RESULTS: Although most participants reported rarely having been told about other options for treatment and could not readily recall many details about specific risks of recommended treatment, they were satisfied with their care. The patients paradoxically described clinicians as displaying caring and empathy despite not explicitly addressing their concerns and worries. We found that the communication domains that underlie shared decision making occurred infrequently, but that participants were still pleased with their role in the decision-making process. We did not find substantially different themes based on where the participant received care or the treatment selected. CONCLUSIONS: Patients were satisfied with all aspects of their care, despite reporting little knowledge about risks or other treatment options, no direct elicitation of worries from providers, and a lack of shared decision making. While the development of effective communication strategies to address these gaps is warranted, their effect on patient-centered outcomes, such as distress and decisional conflict, is unclear. PMID- 27182890 TI - Dual-Modal Imaging-Guided Theranostic Nanocarriers Based on Indocyanine Green and mTOR Inhibitor Rapamycin. AB - The development of treatment protocols that resulted in a complete response to photothermal therapy (PTT) was usually hampered by uneven heat distribution and low effectiveness. Here, we reported an NIR fluorescence and photoacoustic dual modal imaging-guided active targeted thermal sensitive liposomes (TSLs) based on the photothermal therapy agent Indocyanine green (ICG) and antiangiogenesis agent Rapamycin (RAPA) to realize enhanced therapeutic and diagnostic functions. As expected, the in vitro drug release studies exhibited the satisfactory result of drug released from the TSLs under hyperthermia conditions induced by NIR stimulation. The in vitro cellular studies confirmed that the FA-ICG/RAPA-TSLs plus NIR laser exhibited efficient drug accumulation and cytotoxicity in tumor cells and epithelial cells. After 24 h intravenous injection of FA-ICG/RAPA-TSLs, the margins of tumor and normal tissue were accurately identified via the in vivo NIR fluorescence and photoacoustic dual-modal imaging. In addition, FA-ICG/RAPA TSLs combined with NIR irradiation treated tumor-bearing nude mice inhibited tumor growth to a great extent and possessed much lower side effects to normal organs. All detailed evidence suggested that the theranostic TSLs which were capable of enhancing the therapeutic index might be a suitable drug delivery system for dual-modal imaging-guided therapeutic tools for diagnostics as well as the treatment of tumors. PMID- 27182891 TI - Deterministic and Stochastic Study for a Microscopic Angiogenesis Model: Applications to the Lewis Lung Carcinoma. AB - Angiogenesis modelling is an important tool to understand the underlying mechanisms yielding tumour growth. Nevertheless, there is usually a gap between models and experimental data. We propose a model based on the intrinsic microscopic reactions defining the angiogenesis process to link experimental data with previous macroscopic models. The microscopic characterisation can describe the macroscopic behaviour of the tumour, which stability analysis reveals a set of predicted tumour states involving different morphologies. Additionally, the microscopic description also gives a framework to study the intrinsic stochasticity of the reactive system through the resulting Langevin equation. To follow the goal of the paper, we use available experimental information on the Lewis lung carcinoma to infer meaningful parameters for the model that are able to describe the different stages of the tumour growth. Finally we explore the predictive capabilities of the fitted model by showing that fluctuations are determinant for the survival of the tumour during the first week and that available treatments can give raise to new stable tumour dormant states with a reduced vascular network. PMID- 27182893 TI - Polychlorinated Biphenyls in Tree Bark near Former Manufacturing and Incineration Facilities in Sauget, Illinois, United States. AB - We collected 27 tree bark samples near Sauget, IL, where 373 000 mt of polychlorinated biphenyls (PCB) was produced between 1936 and 1977 and 10 245 mt was incinerated from 1971 to 1977. Our goal was observe PCB distribution and apparent movement to residential sites, where 24 of 27 samples were collected. Only one of several waste sites was accessible for sampling. We analyzed for 209 PCB congeners, and 85 peaks are reported (other congeners either coeluted or were near or less than the detection limit). Concentrations of ?PCB ranged from 190 952 to 2 383 988 pg g lipid(-1); 24 of 27 samples had less than 50% of the maximum concentration. Two samples with the highest ?PCB concentrations were downwind from the plant site in residential areas, but both were among the farthest away from the production facility. One high-concentration sample was near the waste site. The three highest concentrations were in trees that were less than 20 years old, showing recent atmospheric PCB mobility. The percentage of ?PCB distributions showed a consistent but variable pattern of diCB to nonaCB congeners. DecaCB was inconsistent, because PCB-209, which was manufactured at the site in Aroclor 1270 and 1271, was the most abundant congener in 10 of the samples but lower in others. PMID- 27182892 TI - Single-Molecule Force Spectroscopy Studies of APOBEC3A-Single-Stranded DNA Complexes. AB - APOBEC3A (A3A) inhibits the replication of a range of viruses and transposons and might also play a role in carcinogenesis. It is a single-domain deaminase enzyme that interacts with single-stranded DNA (ssDNA) and converts cytidines to uridines within specific trinucleotide contexts. Although there is abundant information that describes the potential biological activities of A3A, the interplay between binding ssDNA and sequence-specific deaminase activity remains controversial. Using a single-molecule atomic force microscopy spectroscopy approach developed by Shlyakhtenko et al. [(2015) Sci. Rep. 5, 15648], we determine the stability of A3A in complex with different ssDNA sequences. We found that the strength of the complex is sequence-dependent, with more stable complexes formed with deaminase-specific sequences. A correlation between the deaminase activity of A3A and the complex strength was identified. The ssDNA binding properties of A3A and those for A3G are also compared and discussed. PMID- 27182894 TI - Therapeutic alliance and binge-eating outcomes in a group therapy context. AB - The therapeutic alliance in individual and group psychotherapy is associated with treatment outcomes for a variety of disorders. However, debate persists about the centrality of the alliance in determining positive outcomes. We examined the alliance-outcome relationship across 20 sessions of emotionally focused group therapy (EFGT) for binge-eating disorder (BED). We hypothesized that (1) previous session alliance increase will predict lower subsequent session binge eating level while controlling for previous session binge eating level; and (2) previous session binge eating decline will predict higher subsequent session alliance level while controlling previous session alliance level. Participants were 118 individuals with BED who received 20 sessions of EFGT in 8 groups. Levels of binge eating and therapeutic alliance to the therapist were measured weekly. Linear growth in alliance during group therapy was associated with reduced binge eating at 6 months' posttreatment. We also found that the group's and the individual's alliance scores and binge-eating episodes were significantly associated across treatment, suggesting a mutual influence of the group's and individual's experience of the alliance with the therapist. Regarding the first hypothesis, previous session alliance increase was significantly associated with lower subsequent session binge eating. Regarding the second hypothesis, previous session binge-eating decline was not significantly related to higher subsequent session alliance. The findings provide evidence in a group therapy context for a model in which alliance change influences subsequent symptom levels, but not the other way around. (PsycINFO Database Record PMID- 27182896 TI - Vertebral Osteomyelitis and Acinetobacter Spp. Paravertebral Soft Tissue Infection in a 4-Year-Old Boy With X-Linked Chronic Granulomatous Disease. AB - Vertebral osteomyelitis is known to occur in chronic granulomatous disease, a phagocytic disorder and the etiology is usually a fungus. Indolent spread of fungal infection from lungs to adjacent ribs and vertebra often results in persistent pneumonia and vertebral deformities. We report a 4-year-old boy with chronic cough and kyphosis, who had a fungal vertebral osteomyelitis and Acinetobacter spp. paravertebral soft tissue infection related to X-linked chronic granulomatous disease. PMID- 27182897 TI - Pediatric Latent Tuberculosis: Should Travel and Foreign Birth Testing Criteria Be Reassessed? PMID- 27182895 TI - Fine-needle aspiration and core needle biopsy: An update on 2 common minimally invasive tissue sampling modalities. AB - Fine-needle aspiration (FNA) and core needle biopsy (CNB) represent 2 of the most common minimally invasive tissue sampling modalities. Although similar in many ways, there are significant differences in the collection, processing, interpretation, and suitability for ancillary testing that exist between FNA and CNB. This review provides a brief overview of the strengths and weaknesses of FNA compared with CNB, as well as an update regarding the landscape of recently published studies that investigate the organ-specific comparative performance metrics of FNA and CNB. A current understanding of the benefits and limitations of FNA and CNB will help the cytopathologist and the clinician alike to select the right procedure for the right patient at the right time. Cancer Cytopathol 2016;124:862-870. (c) 2016 American Cancer Society. PMID- 27182898 TI - Ten-Year Study of Acute Otitis Media in Rochester, NY. AB - This review summarizes a prospective, longitudinal 10-year study in Rochester, NY, involving 760 children where virtually all clinically diagnosed acute otitis media (AOM) was confirmed by bacterial culture of middle ear fluid. This review describes detection of otopathogens in middle ear fluid, nasopharyngeal (NP) otopathogen colonization patterns, AOM risk factor analysis, biomarkers of AOM and antibody responses to NP colonization by otopathogens. After licensure of PCV13, there was an immediate drop in AOM caused by Streptococcus pneumoniae (Spn) vaccine serotypes and shortly thereafer an increase in nonvaccine types 16, 21 and 35B. When NP co-colonization occurred, nontypeable Haemophilus influenzae (NTHi) predominated over Spn to cause AOM, and NTHi and Spn both predominated over Moraxella catarrhalis. Transcriptome analysis of peripheral blood mononuclear cells identified unique signatures for NTHi AOM compared with Spn AOM. Elevation of 3 cytokines in serum (S100A12, intercellular adhesion molecule 1 and interleukin 10) accurately predicted the presence and recovery from AOM and the likely otopathogen. NP colonization was an immunizing event. PMID- 27182899 TI - Isolable Diphosphorus-Centered Radical Anion and Diradical Dianion. AB - Two salts containing diphosphorus-centered radical anion 1(*-) and diradical dianion 1(2-**) were obtained by one- and two-electron reductions of an indenofluorene-bridging diphosphaalkene (1) with K and KC8, respectively. The salts have been characterized by electron paramagnetic resonance (EPR) spectroscopy, UV-vis absorption spectroscopy, and single-crystal X-ray diffraction analysis. EPR spectroscopy and theoretical calculations reveal that the spin density of the radicals mainly resides on the phosphorus atoms, and 1(2 **) has an open-shell singlet ground state. 1(*-) and 1(2-**) represent the first isolable and structurally characterized diphosphorus-centered radical anion and dianion. PMID- 27182901 TI - Health Reform and Coverage Changes Among Native Americans. PMID- 27182902 TI - Parenting as Primary Prevention. PMID- 27182903 TI - He Says You Are Finished. PMID- 27182904 TI - -gnosis. PMID- 27182905 TI - The Firearm for Protection? A Risky Bet. PMID- 27182906 TI - The Reality of ICD-10 in the Office. PMID- 27182900 TI - Historical and contemporary stable isotope tracer approaches to studying mammalian protein metabolism. AB - Over a century ago, Frederick Soddy provided the first evidence for the existence of isotopes; elements that occupy the same position in the periodic table are essentially chemically identical but differ in mass due to a different number of neutrons within the atomic nucleus. Allied to the discovery of isotopes was the development of some of the first forms of mass spectrometers, driven forward by the Nobel laureates JJ Thomson and FW Aston, enabling the accurate separation, identification, and quantification of the relative abundance of these isotopes. As a result, within a few years, the number of known isotopes both stable and radioactive had greatly increased and there are now over 300 stable or radioisotopes presently known. Unknown at the time, however, was the potential utility of these isotopes within biological disciplines, it was soon discovered that these stable isotopes, particularly those of carbon (13 C), nitrogen (15 N), oxygen (18 O), and hydrogen (2 H) could be chemically introduced into organic compounds, such as fatty acids, amino acids, and sugars, and used to "trace" the metabolic fate of these compounds within biological systems. From this important breakthrough, the age of the isotope tracer was born. Over the following 80 yrs, stable isotopes would become a vital tool in not only the biological sciences, but also areas as diverse as forensics, geology, and art. This progress has been almost exclusively driven through the development of new and innovative mass spectrometry equipment from IRMS to GC-MS to LC-MS, which has allowed for the accurate quantitation of isotopic abundance within samples of complex matrices. This historical review details the development of stable isotope tracers as metabolic tools, with particular reference to their use in monitoring protein metabolism, highlighting the unique array of tools that are now available for the investigation of protein metabolism in vivo at a whole body down to a single protein level. Importantly, it will detail how this development has been closely aligned to the technological development within the area of mass spectrometry. Without the dedicated development provided by these mass spectrometrists over the past century, the use of stable isotope tracers within the field of protein metabolism would not be as widely applied as it is today, this relationship will no doubt continue to flourish in the future and stable isotope tracers will maintain their importance as a tool within the biological sciences for many years to come. (c) 2016 The Authors. Mass Spectrometry Reviews Published by Wiley Periodicals, Inc. Mass Spec Rev. PMID- 27182907 TI - The Reality of ICD-10 in the Office. PMID- 27182908 TI - Principles for Disclosure of Interests and Management of Conflicts in Guidelines: Desirable and Undesirable Action and Consequences. PMID- 27182909 TI - Principles for Disclosure of Interests and Management of Conflicts in Guidelines: Desirable and Undesirable Action and Consequences. PMID- 27182910 TI - Patient-Initiated Prostate Cancer Screening Among Older U.S. Men. PMID- 27182911 TI - Principles for Disclosure of Interests and Management of Conflicts in Guidelines: Desirable and Undesirable Action and Consequences. PMID- 27182913 TI - Metaplasia. PMID- 27182912 TI - Patient-Initiated Prostate Cancer Screening Among Older U.S. Men. PMID- 27182914 TI - Web Exclusives. The Consult Guys - An MI, a Stent, Bleeding, and Surgery! What Do I Do? PMID- 27182916 TI - Delayed antibiotics reduced antibiotic use in acute respiratory infection without increasing symptom duration. PMID- 27182917 TI - Prednisolone was equivalent to indomethacin for pain reduction in acute gout. PMID- 27182918 TI - Evidence-Based Guideline: CHEST made 20 strong recommendations about antithrombotic therapy for VTE. PMID- 27182919 TI - Review: After lower-extremity DVT, compression stockings do not reduce postthrombotic syndrome or recurrence. PMID- 27182920 TI - Varenicline, combination NRT, and nicotine patch did not differ for smoking cessation at 6 mo. PMID- 27182921 TI - Review: Exercise therapy reduces fatigue in chronic fatigue syndrome. PMID- 27182922 TI - Testosterone gel improved sexual function, but not walk distance or fatigue, in older men with low testosterone. PMID- 27182923 TI - In large-vessel ischemic stroke, adding endovascular thrombectomy to usual care reduced 90-day disability. PMID- 27182924 TI - In patients >= 80 y with NSTEMI or unstable angina, an invasive strategy reduced CV outcomes. PMID- 27182925 TI - Transition care with telemonitoring did not reduce readmission after hospitalization for heart failure. PMID- 27182927 TI - Role of Wasp and the small GTPases RhoA, RhoB, and Cdc42 during capacitation and acrosome reaction in spermatozoa of English guinea pigs. AB - Cytoskeleton remodeling is necessary for capacitation and the acrosome reaction in spermatozoa. F-actin is located in the acrosome and equatorial region during capacitation, but is relocated in the post-acrosomal region during the acrosome reaction in spermatozoa from bull, rat, mice, and guinea pig. Actin polymerization and relocalization are generally regulated by small GTPases that activate Wasp protein, which coordinates with Arp2/3, profilin I, and profilin II to complete cytoskeletal remodeling. This sequence of events is not completely described in spermatozoa, though. Therefore, the aim of this study was to determine if Wasp interacts with small GTPases (RhoA, RhoB, and Cdc42) and proteins (Arp2/3, profilin I, and profilin II) that co-localize with F-actin during capacitation and the acrosome reaction in English guinea pig spermatozoa obtained from the vas deferens. The spermatozoa were capacitated in calcium-free medium, incubated with an activator or an inhibitor of GTPases, and then induced to acrosome react using calcium. The distribution patterns of F-actin were compared to the patterns of Wasp and its putative interaction partners: Wasp and RhoB, but not RhoA or Cdc42, localization overlap with F-actin during capacitation and the acrosome reaction. Activation of small GTPases localized RhoB to the post-acrosomal region whereas their inhibition prevented acrosome exocytosis. Arp2/3 and profilin II appear to interact with Wasp in the post acrosomal region and flagellum, while profilin I and Wasp could be found in the equatorial region. Thus, Wasp and F-actin distribution overlap during capacitation and acrosome reaction, and small GTPases play an important role in cytoskeleton remodeling during these processes in spermatozoa. Mol. Reprod. Dev. 83: 927-937, 2016 (c) 2016 Wiley Periodicals, Inc. PMID- 27182926 TI - Antibiotic Prescriptions and Prophylaxis in Italian Children. Is It Time to Change? Data from the ARPEC Project. AB - BACKGROUND: Antimicrobials are the most commonly prescribed drugs. Many studies have evaluated antibiotic prescriptions in the paediatric outpatient but few studies describing the real antibiotic consumption in Italian children's hospitals have been published. Point-prevalence survey (PPS) has been shown to be a simple, feasible and reliable standardized method for antimicrobials surveillance in children and neonates admitted to the hospital. In this paper, we presented data from a PPS on antimicrobial prescriptions carried out in 7 large Italian paediatric institutions. METHODS: A 1-day PPS on antibiotic use in hospitalized neonates and children was performed in Italy between October and December 2012 as part of the Antibiotic Resistance and Prescribing in European Children project (ARPEC). Seven institutions in seven Italian cities were involved. The survey included all admitted patients less than 18 years of age present in the ward at 8:00 am on the day of the survey, who had at least one on going antibiotic prescription. For all patients data about age, weight, underlying disease, antimicrobial agent, dose and indication for treatment were collected. RESULTS: The PPS was performed in 61 wards within 7 Italian institutions. A total of 899 patients were eligible and 349 (38.9%) had an on going prescription for one or more antibiotics, with variable rates among the hospitals (25.7% - 53.8%). We describe antibiotic prescriptions separately in neonates (<30 days old) and children (> = 30 days to <18 years old). In the neonatal cohort, 62.8% received antibiotics for prophylaxis and only 37.2% on those on antibiotics were treated for infection. Penicillins and aminoglycosides were the most prescribed antibiotic classes. In the paediatric cohort, 64.4% of patients were receiving antibiotics for treatment of infections and 35.5% for prophylaxis. Third generation cephalosporins and penicillin plus inhibitors were the top two antibiotic classes. The main reason for prescribing antibiotic therapy in children was lower respiratory tract infections (LRTI), followed by febrile neutropenia/fever in oncologic patients, while, in neonates, sepsis was the most common indication for treatment. Focusing on prescriptions for LRTI, 43.3% of patients were treated with 3rd generation cephalosporins, followed by macrolides (26.9%), quinolones (16.4%) and carbapenems (14.9%) and 50.1% of LRTI cases were receiving more than one antibiotic. For neutropenic fever/fever in oncologic patients, the preferred antibiotics were penicillins with inhibitors (47.8%), followed by carbapenems (34.8%), aminoglycosides (26.1%) and glycopeptides (26.1%). Overall, the 60.9% of patients were treated with a combination therapy. CONCLUSIONS: Our study provides insight on the Italian situation in terms of antibiotic prescriptions in hospitalized neonates and children. An over-use of third generation cephalosporins both for prophylaxis and treatment was the most worrisome finding. A misuse and abuse of carbapenems and quinolones was also noted. Antibiotic stewardship programs should immediately identify feasible targets to monitor and modify the prescription patterns in children's hospital, also considering the continuous and alarming emergence of MDR bacteria. PMID- 27182928 TI - Efficacy of Cognitive-Behavioral Therapy in Pediatric Obsessive-Compulsive Disorder: A Meta-Analysis. AB - BACKGROUND Pediatric obsessive-compulsive disorder (OCD) is a debilitating psychological anxiety disorder. Cognitive-behavioral therapy (CBT) has been shown to be an effective therapy for OCD, but the evaluation results from various studies are inconsistent and incomprehensive. This meta-analysis examined the efficacy of CBT in treatment of OCD. MATERIAL AND METHODS A literature search identified 13 studies that met the inclusion criteria. The efficacy of CBT on OCD was evaluated by comparing post-treatment and pre-treatment Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) scores. Weighted mean difference (WMD) was generated for the statistical evaluation. Heterogeneity was evaluated by I2 index. RESULTS A decrease in WMD and a statistical significance (p<0.0001) in both CY-BOCS and CGI scores between pre- and post-CBT treatment were observed in both overall database (-11.73) and USA subgroup (-11.371), which indicates a dramatic relief of OCD symptoms after CBT treatment. Heterogeneity was detected in overall database and USA subgroup, which resulted in an application of the random-effects model to both groups. Publication bias was examined by both Begg's funnel plot and Egger's test and no publication bias was detected. CONCLUSIONS We concluded that CBT is efficacious in treating children's OCD. PMID- 27182930 TI - Cs3W3PO13: A Tungsten Phosphate with One-Dimensional Zigzag Tunnels Exhibiting Strongly Anisotropic Thermal Expansion. AB - A new tungsten phosphate, Cs3W3PO13, is synthesized using the high-temperature flux method. Cs3W3PO13 crystallizes in the space group Pnma and contains one dimensional zigzag tunnels, which are found for the first time in tungsten phosphate. This highly anisotropic structural feature results in a very strong anisotropic thermal expansion, with thermal expansion coefficients of 14.15 +/- 1.11 and 0.72 +/- 0.22 M K(-1) along the a and b axes, respectively, over the temperature range from 13 to 270 K. In addition, thermal analysis, UV-vis-near-IR diffuse reflectance, and first-principles electronic structure calculations on Cs3W3PO13 are performed. PMID- 27182929 TI - Macropinosomes are Key Players in Early Shigella Invasion and Vacuolar Escape in Epithelial Cells. AB - Intracellular pathogens include all viruses, many bacteria and parasites capable of invading and surviving within host cells. Key to survival is the subversion of host cell pathways by the pathogen for the purpose of propagation and evading the immune system. The intracellular bacterium Shigella flexneri, the causative agent of bacillary dysentery, invades host cells in a vacuole that is subsequently ruptured to allow growth of the pathogen within the host cytoplasm. S. flexneri invasion has been classically described as a macropinocytosis-like process, however the underlying details and the role of macropinosomes in the intracellular bacterial lifestyle have remained elusive. We applied dynamic imaging and advanced large volume correlative light electron microscopy (CLEM) to study the highly transient events of S. flexneri's early invasion into host epithelial cells and elucidate some of its fundamental features. First, we demonstrate a clear distinction between two compartments formed during the first step of invasion: the bacterial containing vacuole and surrounding macropinosomes, often considered identical. Next, we report a functional link between macropinosomes and the process of vacuolar rupture, demonstrating that rupture timing is dependent on the availability of macropinosomes as well as the activity of the small GTPase Rab11 recruited directly to macropinosomes. We go on to reveal that the bacterial containing vacuole and macropinosomes come into direct contact at the onset of vacuolar rupture. Finally, we demonstrate that S. flexneri does not subvert pre-existing host endocytic vesicles during the invasion steps leading to vacuolar rupture, and propose that macropinosomes are the major compartment involved in these events. These results provide the basis for a new model of the early steps of S. flexneri epithelial cell invasion, establishing a different view of the enigmatic process of cytoplasmic access by invasive bacterial pathogens. PMID- 27182931 TI - A Metal and Base-Free Chemoselective Primary Amination of Boronic Acids Using Cyanamidyl/Arylcyanamidyl Radical as Aminating Species: Synthesis and Mechanistic Studies by Density Functional Theory. AB - An efficient, metal and base-free, chemoselective synthesis of aryl-, heteroaryl , and alkyl primary amines from the corresponding boronic acids has been achieved at ambient temperature mediated by [bis(trifluoroacetoxy)iodo]benzene (PIFA) and N-bromosuccinimide (NBS) using cyanamidyl/arylcyanamidyl radicals as the aminating species. The primary amine compounds were initially obtained as their corresponding ammonium trifluoroacetate salts which, on treatment with aq NaOH, provide the free amines. Finally, the primary amines were isolated through column chromatography over silica-gel using hexane-EtOAc solvent system as the eluent. The reactions are sufficiently fast, completing within 1 h. Quantum chemical calculations in combination with experimental observations validate that the ipso amination of substituted boronic acids involves the formation of cyanamidyl/arylcyanamidyl radical, followed by regiospecific interaction of its nitrile-N center with boron atom of the boronic acids, leading to chemoselective primary amination. PMID- 27182942 TI - Quantitative evaluation of ABC transporter-mediated drug resistance based on the determination of the anticancer activity of camptothecin against breast cancer stem cells using TIRF. AB - Elevated expression of drug efflux pumps such as multidrug resistant protein-1 (MDR1/ABCB1) and multidrug resistance associated protein-1 (MRP1/ABCC1) in cancer stem cells (CSCs) among a bulky tumor cell population was attributed to drug resistance. For the first time, we have quantitatively evaluated the cytotoxic profile of camptothecin (CPT) against the CSC. In the present study, a Qdot based total internal reflection fluorescence (TIRF) detection system effectively interpreted that drug resistance to CPT was reduced in the CSC under ABCB1 inhibited conditions. This study revealed that quantitative finding of the EC50 value for apoptosis and necrosis in correlation with the ABC inhibitor and CSC population using TIRF could provide more details of the anti-cancer efficacy of chemotherapeutic agents. PMID- 27182944 TI - A Novel Strategy for Exploitation of Host RNase E Activity by a Marine Cyanophage. AB - Previous studies have shown that infection of Prochlorococcus MED4 by the cyanophage P-SSP7 leads to increased transcript levels of host endoribonuclease (RNase) E. However, it has remained enigmatic whether this is part of a host defense mechanism to degrade phage messenger RNA (mRNA) or whether this single strand RNA-specific RNase is utilized by the phage. Here we describe a hitherto unknown means through which this cyanophage increases expression of RNase E during phage infection and concomitantly protects its own RNA from degradation. We identified two functionally different RNase E mRNA variants, one of which is significantly induced during phage infection. This transcript lacks the 5' UTR, is considerably more stable than the other transcript, and is likely responsible for increased RNase E protein levels during infection. Furthermore, selective enrichment and in vivo analysis of double-stranded RNA (dsRNA) during infection revealed that phage antisense RNAs (asRNAs) sequester complementary mRNAs to form dsRNAs, such that the phage protein-coding transcriptome is nearly completely covered by asRNAs. In contrast, the host protein-coding transcriptome is only partially covered by asRNAs. These data suggest that P-SSP7 orchestrates degradation of host RNA by increasing RNase E expression while masking its own transcriptome from RNase E degradation in dsRNA complexes. We propose that this combination of strategies contributes significantly to phage progeny production. PMID- 27182943 TI - Long-Term Memory in Drosophila Is Influenced by Histone Deacetylase HDAC4 Interacting with SUMO-Conjugating Enzyme Ubc9. AB - HDAC4 is a potent memory repressor with overexpression of wild type or a nuclear restricted mutant resulting in memory deficits. Interestingly, reduction of HDAC4 also impairs memory via an as yet unknown mechanism. Although histone deacetylase family members are important mediators of epigenetic mechanisms in neurons, HDAC4 is predominantly cytoplasmic in the brain and there is increasing evidence for interactions with nonhistone proteins, suggesting HDAC4 has roles beyond transcriptional regulation. To that end, we performed a genetic interaction screen in Drosophila and identified 26 genes that interacted with HDAC4, including Ubc9, the sole SUMO E2-conjugating enzyme. RNA interference-induced reduction of Ubc9 in the adult brain impaired long-term memory in the courtship suppression assay, a Drosophila model of associative memory. We also demonstrate that HDAC4 and Ubc9 interact genetically during memory formation, opening new avenues for investigating the mechanisms through which HDAC4 regulates memory formation and other neurological processes. PMID- 27182945 TI - Genomic Conflicts that Cause Pollen Mortality and Raise Reproductive Barriers in Arabidopsis thaliana. AB - Species differentiation and the underlying genetics of reproductive isolation are central topics in evolutionary biology. Hybrid sterility is one kind of reproductive barrier that can lead to differentiation between species. Here, we analyze the complex genetic basis of the intraspecific hybrid male sterility that occurs in the offspring of two distant natural strains of Arabidopsis thaliana, Shahdara and Mr-0, with Shahdara as the female parent. Using both classical and quantitative genetic approaches as well as cytological observation of pollen viability, we demonstrate that this particular hybrid sterility results from two causes of pollen mortality. First, the Shahdara cytoplasm induces gametophytic cytoplasmic male sterility (CMS) controlled by several nuclear loci. Second, several segregation distorters leading to allele-specific pollen abortion (pollen killers) operate in hybrids with either cytoplasm. The complete sterility of the hybrid with the Shahdara cytoplasm results from the genetic linkage of the two causes of pollen mortality, i.e., CMS nuclear determinants and pollen killers. Furthermore, natural variation at these loci in A. thaliana is associated with different male-sterility phenotypes in intraspecific hybrids. Our results suggest that the genomic conflicts that underlie segregation distorters and CMS can concurrently lead to reproductive barriers between distant strains within a species. This study provides a new framework for identifying molecular mechanisms and the evolutionary history of loci that contribute to reproductive isolation, and possibly to speciation. It also suggests that two types of genomic conflicts, CMS and segregation distorters, may coevolve in natural populations. PMID- 27182946 TI - Hybrid Sterility in Rice (Oryza sativa L.) Involves the Tetratricopeptide Repeat Domain Containing Protein. AB - Intersubspecific hybrid sterility is a common form of reproductive isolation in rice (Oryza sativa L.), which significantly hampers the utilization of heterosis between indica and japonica varieties. Here, we elucidated the mechanism of S7, which specially causes Aus-japonica/indica hybrid female sterility, through cytological and genetic analysis, map-based cloning, and transformation experiments. Abnormal positioning of polar nuclei and smaller embryo sac were observed in F1 compared with male and female parents. Female gametes carrying S7(cp) and S7(i) were aborted in S7(ai)/S7(cp) and S7(ai)/S7(i), respectively, whereas they were normal in both N22 and Dular possessing a neutral allele, S7(n) S7 was fine mapped to a 139-kb region in the centromere region on chromosome 7, where the recombination was remarkably suppressed due to aggregation of retrotransposons. Among 16 putative open reading frames (ORFs) localized in the mapping region, ORF3 encoding a tetratricopeptide repeat domain containing protein was highly expressed in the pistil. Transformation experiments demonstrated that ORF3 is the candidate gene: downregulated expression of ORF3 restored spikelet fertility and eliminated absolutely preferential transmission of S7(ai) in heterozygote S7(ai)/S7(cp); sterility occurred in the transformants Cpslo17-S7(ai) Our results may provide implications for overcoming hybrid embryo sac sterility in intersubspecific hybrid rice and utilization of hybrid heterosis for cultivated rice improvement. PMID- 27182948 TI - Two-Locus Likelihoods Under Variable Population Size and Fine-Scale Recombination Rate Estimation. AB - Two-locus sampling probabilities have played a central role in devising an efficient composite-likelihood method for estimating fine-scale recombination rates. Due to mathematical and computational challenges, these sampling probabilities are typically computed under the unrealistic assumption of a constant population size, and simulation studies have shown that resulting recombination rate estimates can be severely biased in certain cases of historical population size changes. To alleviate this problem, we develop here new methods to compute the sampling probability for variable population size functions that are piecewise constant. Our main theoretical result, implemented in a new software package called LDpop, is a novel formula for the sampling probability that can be evaluated by numerically exponentiating a large but sparse matrix. This formula can handle moderate sample sizes ([Formula: see text]) and demographic size histories with a large number of epochs ([Formula: see text]). In addition, LDpop implements an approximate formula for the sampling probability that is reasonably accurate and scales to hundreds in sample size ([Formula: see text]). Finally, LDpop includes an importance sampler for the posterior distribution of two-locus genealogies, based on a new result for the optimal proposal distribution in the variable-size setting. Using our methods, we study how a sharp population bottleneck followed by rapid growth affects the correlation between partially linked sites. Then, through an extensive simulation study, we show that accounting for population size changes under such a demographic model leads to substantial improvements in fine-scale recombination rate estimation. PMID- 27182947 TI - Timely Closure of the Prospore Membrane Requires SPS1 and SPO77 in Saccharomyces cerevisiae. AB - During sporulation in Saccharomyces cerevisiae, a double lipid bilayer called the prospore membrane is formed de novo, growing around each meiotic nucleus and ultimately closing to create four new cells within the mother cell. Here we show that SPS1, which encodes a kinase belonging to the germinal center kinase III family, is involved in prospore membrane development and is required for prospore membrane closure. We find that SPS1 genetically interacts with SPO77 and see that loss of either gene disrupts prospore membrane closure in a similar fashion. Specifically, cells lacking SPS1 and SPO77 produce hyperelongated prospore membranes from which the leading edge protein complex is not removed from the prospore membrane in a timely fashion. The SPS1/SPO77 pathway is required for the proper phosphorylation and stability of Ssp1, a member of the leading edge protein complex that is removed and degraded when the prospore membrane closes. Genetic dissection of prospore membrane closure finds SPS1 and SPO77 act in parallel to a previously described pathway of prospore membrane closure that involves AMA1, an activator of the meiotic anaphase promoting complex. PMID- 27182949 TI - Determinants of Genetic Diversity of Spontaneous Drug Resistance in Bacteria. AB - Any pathogen population sufficiently large is expected to harbor spontaneous drug resistant mutants, often responsible for disease relapse after antibiotic therapy. It is seldom appreciated, however, that while larger populations harbor more mutants, the abundance distribution of these mutants is expected to be markedly uneven. This is because a larger population size allows early mutants to expand for longer, exacerbating their predominance in the final mutant subpopulation. Here, we investigate the extent to which this reduction in evenness can constrain the genetic diversity of spontaneous drug resistance in bacteria. Combining theory and experiments, we show that even small variations in growth rate between resistant mutants and the wild type result in orders-of magnitude differences in genetic diversity. Indeed, only a slight fitness advantage for the mutant is enough to keep diversity low and independent of population size. These results have important clinical implications. Genetic diversity at antibiotic resistance loci can determine a population's capacity to cope with future challenges (i.e., second-line therapy). We thus revealed an unanticipated way in which the fitness effects of antibiotic resistance can affect the evolvability of pathogens surviving a drug-induced bottleneck. This insight will assist in the fight against multidrug-resistant microbes, as well as contribute to theories aimed at predicting cancer evolution. PMID- 27182951 TI - Local Joint Testing Improves Power and Identifies Hidden Heritability in Association Studies. AB - There is mounting evidence that complex human phenotypes are highly polygenic, with many loci harboring multiple causal variants, yet most genetic association studies examine each SNP in isolation. While this has led to the discovery of thousands of disease associations, discovered variants account for only a small fraction of disease heritability. Alternative multi-SNP methods have been proposed, but issues such as multiple-testing correction, sensitivity to genotyping error, and optimization for the underlying genetic architectures remain. Here we describe a local joint-testing procedure, complete with multiple testing correction, that leverages a genetic phenomenon we call linkage masking wherein linkage disequilibrium between SNPs hides their signal under standard association methods. We show that local joint testing on the original Wellcome Trust Case Control Consortium (WTCCC) data set leads to the discovery of 22 associated loci, 5 more than the marginal approach. These loci were later found in follow-up studies containing thousands of additional individuals. We find that these loci significantly increase the heritability explained by genome-wide significant associations in the WTCCC data set. Furthermore, we show that local joint testing in a cis-expression QTL (eQTL) study of the gEUVADIS data set increases the number of genes containing significant eQTL by 10.7% over marginal analyses. Our multiple-hypothesis correction and joint-testing framework are available in a python software package called Jester, available at github.com/brielin/Jester. PMID- 27182950 TI - The Activity-Dependent Regulation of Protein Kinase Stability by the Localization to P-Bodies. AB - The eukaryotic cytoplasm contains a variety of ribonucleoprotein (RNP) granules in addition to the better-understood membrane-bound organelles. These granules form in response to specific stress conditions and contain a number of signaling molecules important for the control of cell growth and survival. However, relatively little is known about the mechanisms responsible for, and the ultimate consequences of, this protein localization. Here, we show that the Hrr25/CK1delta protein kinase is recruited to cytoplasmic processing bodies (P-bodies) in an evolutionarily conserved manner. This recruitment requires Hrr25 kinase activity and the Dcp2 decapping enzyme, a core constituent of these RNP granules. Interestingly, the data indicate that this localization sequesters active Hrr25 away from the remainder of the cytoplasm and thereby shields this enzyme from the degradation machinery during these periods of stress. Altogether, this work illustrates how the presence within an RNP granule can alter the ultimate fate of the localized protein. PMID- 27182952 TI - Resolving the Conflict Between Associative Overdominance and Background Selection. AB - In small populations, genetic linkage between a polymorphic neutral locus and loci subject to selection, either against partially recessive mutations or in favor of heterozygotes, may result in an apparent selective advantage to heterozygotes at the neutral locus (associative overdominance) and a retardation of the rate of loss of variability by genetic drift at this locus. In large populations, selection against deleterious mutations has previously been shown to reduce variability at linked neutral loci (background selection). We describe analytical, numerical, and simulation studies that shed light on the conditions under which retardation vs. acceleration of loss of variability occurs at a neutral locus linked to a locus under selection. We consider a finite, randomly mating population initiated from an infinite population in equilibrium at a locus under selection. With mutation and selection, retardation occurs only when S, the product of twice the effective population size and the selection coefficient, is of order 1. With S >> 1, background selection always causes an acceleration of loss of variability. Apparent heterozygote advantage at the neutral locus is, however, always observed when mutations are partially recessive, even if there is an accelerated rate of loss of variability. With heterozygote advantage at the selected locus, loss of variability is nearly always retarded. The results shed light on experiments on the loss of variability at marker loci in laboratory populations and on the results of computer simulations of the effects of multiple selected loci on neutral variability. PMID- 27182954 TI - Assessment of Registered Dietitians' Beliefs and Practices for a Nutrition Counselling Approach. AB - PURPOSE: This study describes registered dietitians' (RDs) perceptions and use of a nutrition counselling approach (NCA) as defined by the American Academy of Nutrition and Dietetics Nutrition Care Process terminology (NCPT). METHODS: A cross-sectional online survey was administered to approximately 500 RDs in Alberta, Canada. Items included demographics, job characteristics, perceived knowledge, competence, use of an NCA, training experience, and theory of planned behaviour salient beliefs. Descriptive analyses compared RDs who counselled "all or most" of their clients with those who counselled "some or none." Salient beliefs were analyzed using content analysis. RESULTS: Of the 349 RDs who completed the survey, 64.2% provided an NCA to "all or most" of their patients. RDs were supportive of using an NCA (mean = 8.7/10, SD = 1.9) and most RDs (84.5%) had received training on an NCA. Salient beliefs included advantages (e.g., improved behaviour change in patients) and disadvantages (e.g., inadequate time). Normative referents included colleagues (e.g., multidisciplinary team), managers, patients/clients, College of RDs of Alberta, and counsellors. The barriers and enablers were related to patients' situations, infrastructure, and RD supports. CONCLUSIONS: These results may enable decision makers to more effectively design and target training and implementation programs to improve RDs' NCA. PMID- 27182953 TI - Development and Genetic Characterization of an Advanced Backcross-Nested Association Mapping (AB-NAM) Population of Wild * Cultivated Barley. AB - The ability to access alleles from unadapted germplasm collections is a long standing problem for geneticists and breeders. Here we developed, characterized, and demonstrated the utility of a wild barley advanced backcross-nested association mapping (AB-NAM) population. We developed this population by backcrossing 25 wild barley accessions to the six-rowed malting barley cultivar Rasmusson. The 25 wild barley parents were selected from the 318 accession Wild Barley Diversity Collection (WBDC) to maximize allelic diversity. The resulting 796 BC2F4:6 lines were genotyped with 384 SNP markers, and an additional 4022 SNPs and 263,531 sequence variants were imputed onto the population using 9K iSelect SNP genotypes and exome capture sequence of the parents, respectively. On average, 96% of each wild parent was introgressed into the Rasmusson background, and the population exhibited low population structure. While linkage disequilibrium (LD) decay (r(2) = 0.2) was lowest in the WBDC (0.36 cM), the AB NAM (9.2 cM) exhibited more rapid LD decay than comparable advanced backcross (28.6 cM) and recombinant inbred line (32.3 cM) populations. Three qualitative traits: glossy spike, glossy sheath, and black hull color were mapped with high resolution to loci corresponding to known barley mutants for these traits. Additionally, a total of 10 QTL were identified for grain protein content. The combination of low LD, negligible population structure, and high diversity in an adapted background make the AB-NAM an important tool for high-resolution gene mapping and discovery of novel allelic variation using wild barley germplasm. PMID- 27182955 TI - Performance evaluation of an automated electrochemiluminescent calcitonin (CT) immunoassay in diagnosis of medullary thyroid carcinoma. AB - OBJECTIVES: The aim was to evaluate the Elecsys(r) hCT electrochemiluminescence immunoassay on the immunoanalyser Cobas e411. DESIGN AND METHODS: Within-run, between-run imprecision, linearity, recovery after dilution, the high dose hook effect, as well as the stability of calcitonin were examined. A method comparison to an established immunoradiometric assay was executed in 135 routine plasma samples. RESULTS: Within- and between-run imprecision CVs were <=1.4% and <=2.5%, respectively. The Elecsys(r) hCT assay was linear over the measuring range of 0.5 2000ng/L. Recoveries after dilution of a high sample in Diluent MultiAssay were within the range of 95% to 97%. The high dose hook point occurred at an hCT concentration of 56,000ng/L. Calcitonin was found to be stable up to 5h at RT, up to 24h at 2-8 degrees C and up to one month at -20 degrees and -80 degrees C. Passing Bablok regression analysis showed no significant deviation from linearity (p=0.10) with a slope of 1.00 (95% CI 0.95-1.06) and an intercept of -0.81 (95%CI -1.01 to -0.46). CONCLUSIONS: The Elecsys(r) hCT immunoassay provides precision and reliability in combination with reduced turnaround time as compared to the hCT IRMA. PMID- 27182956 TI - Disseminated Mycobacterium chelonae infection in a patient with T-cell lymphoma. AB - Infections with rapidly growing mycobacteria are rare and most often seen in immunocompromised patients. We herein present the case of a 69-year-old man with a T-cell lymphoma treated by chemotherapy and mogamulizumab with a 6-month history of febrile episodes and subcutaneous nodules in both arms and arthritis of metacarpophalangeal joints. Blood cultures and DNA sequencing results demonstrated the growth of Mycobacterium chelonae. The patient was successfully treated with clarithromycin, moxifloxacin, and tobramycin, but died shortly after due to lymphoma progression. PMID- 27182957 TI - Superoxide generated from the glutathione-mediated reduction of selenite damages the iron-sulfur cluster of chloroplastic ferredoxin. AB - Selenium assimilation in plants is facilitated by several enzymes that participate in the transport and assimilation of sulfate. Manipulation of genes that function in sulfur metabolism dramatically affects selenium toxicity and accumulation. However, it has been proposed that selenite is not reduced by sulfite reductase. Instead, selenite can be non-enzymatically reduced by glutathione, generating selenodiglutathione and superoxide. The damaging effects of superoxide on iron-sulfur clusters in cytosolic and mitochondrial proteins are well known. However, it is unknown if superoxide damages chloroplastic iron sulfur proteins. The goals of this study were twofold: to determine whether decreased activity of sulfite reductase impacts selenium tolerance in Arabidopsis, and to determine if superoxide generated from the glutathione mediated reduction of selenite damages the iron-sulfur cluster of ferredoxin. Our data demonstrate that knockdown of sulfite reductase in Arabidopsis does not affect selenite tolerance or selenium accumulation. Additionally, we provide in vitro evidence that the non-enzymatic reduction of selenite damages the iron sulfur cluster of ferredoxin, a plastidial protein that is an essential component of the photosynthetic light reactions. Damage to ferredoxin's iron-sulfur cluster was associated with formation of apo-ferredoxin and impaired activity. We conclude that if superoxide damages iron-sulfur clusters of ferredoxin in planta, then it might contribute to photosynthetic impairment often associated with abiotic stress, including toxic levels of selenium. PMID- 27182958 TI - Seed-borne endophytic Bacillus amyloliquefaciens RWL-1 produces gibberellins and regulates endogenous phytohormones of Oryza sativa. AB - Some microorganisms are adapted to an endophytic mode, living symbiotically with plants through vertical transmission in seeds. The role of plant growth-promoting endophytes has been well studied, but those of seed-associated endophytic bacteria are less understood. The current study aimed to isolate and identify bacterial endophytes associated with rice (Oryza sativa L. 'Jin so mi') seeds, their potential to produce gibberellins (GAs), and role in improving host-plant physiology. The isolated bacterial endophyte RWL-1 was identified as Bacillus amyloliquefaciens by using 16S rRNA sequencing and phylogenetic analysis. The pure culture of B. amyloliquefaciens RWL-1, supplied with deuterated internal standards, was subjected to gas chromatography and mass spectrometric selected ion monitoring (GC-MS/SIM) for quantification of GAs. Results showed the presence of GAs in various quantities (ng/mL) viz., GA20 (17.88 +/- 4.04), GA36 (5.75 +/- 2.36), GA24 (5.64 +/- 2.46), GA4 (1.02 +/- 0.16), GA53 (0.772 +/- 0.20), GA9 (0.12 +/- 0.09), GA19 (0.093 +/- 0.13), GA5 (0.08 +/- 0.04), GA12 (0.014 +/- 0.34), and GA8 (0.013 +/- 0.01). Since endogenous seed GAs are essential for prolonged seed growth and subsequent plant development, we used exogenous GA3 as a positive control and water as a negative control for comparative analysis of the application of B. amyloliquefaciens RWL-1 to rice plants. The growth parameters of rice plants treated with endophytic bacterial cell application was significantly increased compared to the plants treated with exogenous GA3 and water. This was also revealed by the significant up-regulation of endogenous GA1 (17.54 +/- 2.40 ng), GA4 (310 +/- 5.41 ng), GA7 (192.60 +/- 3.32 ng), and GA9 (19.04 +/- 2.49 ng) as compared to results of the positive and negative control treatments. Rice plants inoculated with B. amyloliquefaciens RWL-1 exhibited significantly higher endogenous salicylic acid (1615.06 +/- 10.81 MUg), whereas endogenous abscisic acid (23.31 +/- 2.76 ng) and jasmonic acid (25.51 +/- 4.20 ng) were observed to be significantly lower in these inoculated plants than in those treated with exogenous GA3 and water. Results of the present study suggest that B. amyloliquefaciens RWL-1 has the ability to produce GAs and that its inoculation in seedlings can be beneficial to rice plants. Broader field trials should be conducted to determine its use as an alternative biofertilizer. PMID- 27182959 TI - Targeted exonic sequencing of GWAS loci in the high extremes of the plasma lipids distribution. AB - OBJECTIVE: Genome-wide association studies (GWAS) for plasma lipid levels have mapped numerous genomic loci, with each region often containing many protein coding genes. Targeted re-sequencing of exons is a strategy to pinpoint causal variants and genes. METHODS: We performed solution-based hybrid selection of 9008 exons at 939 genes within 95 GWAS loci for plasma lipid levels and sequenced using next-generation sequencing technology individuals with extremely high as well as low to normal levels of low-density lipoprotein cholesterol (LDL-C, n = 311; mean low = 71 mg/dl versus high = 241 mg/dl), triglycerides (TG, n = 308; mean low = 75 mg/dl versus high = 1938 mg/dl), and high-density lipoprotein cholesterol (HDL-C, n = 684; mean low = 32 mg/dl versus high = 102 mg/dl). We identified 15,002 missense, nonsense, or splice site variants with a frequency <5%. We tested whether coding sequence variants, individually or aggregated within a gene, were associated with plasma lipid levels. To replicate findings, we performed sequencing in independent participants (n = 6424). RESULTS: Across discovery and replication sequencing, we found 6 variants with significant associations with plasma lipids. Of these, one was a novel association: p.Ser147Asn variant in APOA4 (14.3% frequency, TG OR = 0.49, P = 7.1 * 10(-4)) with TG. In gene-level association analyses where rare variants within each gene are collapsed, APOC3 (P = 2.1 * 10(-5)) and LDLR (P = 5.0 * 10(-12)) were associated with plasma lipids. CONCLUSIONS: After sequencing genes from 95 GWAS loci in participants with extremely high plasma lipid levels, we identified one new coding variant associated with TG. These results provide insight regarding design of similar sequencing studies with respect to sample size, follow-up, and analysis methodology. PMID- 27182961 TI - Role of endothelial permeability hotspots and endothelial mitosis in determining age-related patterns of macromolecule uptake by the rabbit aortic wall near branch points. AB - BACKGROUND AND AIMS: Transport of macromolecules between plasma and the arterial wall plays a key role in atherogenesis. Scattered hotspots of elevated endothelial permeability to macromolecules occur in the aorta; a fraction of them are associated with dividing cells. Hotspots occur particularly frequently downstream of branch points, where lesions develop in young rabbits and children. However, the pattern of lesions varies with age, and can be explained by similar variation in the pattern of macromolecule uptake. We investigated whether patterns of hotspots and mitosis also change with age. METHODS: Evans' Blue dye labeled albumin was injected intravenously into immature or mature rabbits and its subsequent distribution in the aortic wall around intercostal branch ostia examined by confocal microscopy and automated image analysis. Mitosis was detected by immunofluorescence after adding 5-bromo-2-deoxiuridine to drinking water. RESULTS: Hotspots were most frequent downstream of branches in immature rabbits, but a novel distribution was observed in mature rabbits. Neither pattern was explained by mitosis. Hotspot uptake correlated spatially with the much greater non-hotspot uptake (p < 0.05), and the same pattern was seen when only the largest hotspots were considered. CONCLUSIONS: The pattern of hotspots changes with age. The data are consistent with there being a continuum of local permeabilities rather than two distinct mechanisms. The distribution of the dye, which binds to elastin and collagen, was similar to that of non-binding tracers and to lesions apart from a paucity at the lateral margins of branches that can be explained by lower levels of fibrous proteins in those regions. PMID- 27182960 TI - The predictive value of the borderline ankle-brachial index for long-term clinical outcomes: An observational cohort study. AB - BACKGROUND AND AIMS: Low ankle-brachial index (ABI) is associated with increased mortality and an increased incidence of cardiovascular events. The purpose of this study was to investigate the value of borderline ABI in predicting clinical outcomes. METHODS AND RESULTS: The data were derived from the Shinken Database 2004-2012, from a single hospital-based cohort study (N = 19,994). ABI was measured in 5205 subjects; 4756 subjects whose ABI was 0.91-1.39 and having no history of peripheral artery disease were enrolled. The subjects were classified into two groups as follows: borderline ABI (0.91-1.00; n = 324) and normal ABI (1.01-1.39; n = 4432). Subjects in the borderline ABI group had more comorbidities, including diabetes mellitus, aortic disease, and stroke. Moreover, the borderline ABI group was associated with higher levels of hemoglobin A1c and brain natriuretic peptide, larger diameters of left atrium and left ventricle, and lower levels of estimated glomerular filtration rate and left ventricular ejection fraction. All-cause death and cardiovascular death occurred in 9.3% and 4.6% of subjects in the borderline ABI group, and in 2.0% and 0.8% of subjects in the normal ABI group, respectively. An adjusted Cox regression model showed that borderline ABI was associated with a higher incidence of all-cause death (hazard ratio [HR] 2.27, p = 0.005) and cardiovascular death (HR 3.47, p = 0.003). CONCLUSION: A borderline ABI was independently associated with worse clinical outcomes in relatively high risk population. Our data should be confirmed in larger populations including those with low risk profiles. PMID- 27182963 TI - Choreoathetosis, Dystonia, and Myoclonus in 3 Siblings With Autosomal Recessive Spinocerebellar Ataxia Type 16. PMID- 27182962 TI - SparkBWA: Speeding Up the Alignment of High-Throughput DNA Sequencing Data. AB - Next-generation sequencing (NGS) technologies have led to a huge amount of genomic data that need to be analyzed and interpreted. This fact has a huge impact on the DNA sequence alignment process, which nowadays requires the mapping of billions of small DNA sequences onto a reference genome. In this way, sequence alignment remains the most time-consuming stage in the sequence analysis workflow. To deal with this issue, state of the art aligners take advantage of parallelization strategies. However, the existent solutions show limited scalability and have a complex implementation. In this work we introduce SparkBWA, a new tool that exploits the capabilities of a big data technology as Spark to boost the performance of one of the most widely adopted aligner, the Burrows-Wheeler Aligner (BWA). The design of SparkBWA uses two independent software layers in such a way that no modifications to the original BWA source code are required, which assures its compatibility with any BWA version (future or legacy). SparkBWA is evaluated in different scenarios showing noticeable results in terms of performance and scalability. A comparison to other parallel BWA-based aligners validates the benefits of our approach. Finally, an intuitive and flexible API is provided to NGS professionals in order to facilitate the acceptance and adoption of the new tool. The source code of the software described in this paper is publicly available at https://github.com/citiususc/SparkBWA, with a GPL3 license. PMID- 27182964 TI - Admixture analysis of age at onset in first episode bipolar disorder. AB - BACKGROUND: Many studies have used the admixture analysis to separate age-at onset (AAO) subgroups in bipolar disorder, but none of them examined first episode patients. OBJECTIVE: The purpose of this study was to investigate the influence of clinical variables on AAO in first episode bipolar patients. METHODS: The admixture analysis was applied to identify the model best fitting the observed AAO distribution of a sample of 194 patients with DSM-IV diagnosis of bipolar disorder and the finite mixture model was applied to assess the effect of clinical covariates on AAO. RESULTS: Using the BIC method, the model that was best fitting the observed distribution of AAO was a mixture of three normal distributions. We identified three AAO groups: early age-at-onset (EAO) (u=18.0, sigma=2.88), intermediate-age-at-onset (IAO) (u=28.7, sigma=3.5), and late-age-at onset (LAO) (u=47.3, sigma=7.8), comprising 69%, 22%, and 9% of the sample respectively. Our first episode sample distribution model was significantly different from most of the other studies that applied the mixture analysis. LIMITATIONS: The main limitation is that our sample may have inadequate statistical power to detect the clinical associations with the AAO subgroups. CONCLUSIONS: This study confirms that bipolar disorder can be classified into three groups based on AAO distribution. The data reported in our paper provide more insight into the diagnostic heterogeneity of bipolar disorder across the three AAO subgroups. PMID- 27182965 TI - Detection and interpretation of shared genetic influences on 42 human traits. AB - We performed a scan for genetic variants associated with multiple phenotypes by comparing large genome-wide association studies (GWAS) of 42 traits or diseases. We identified 341 loci (at a false discovery rate of 10%) associated with multiple traits. Several loci are associated with multiple phenotypes; for example, a nonsynonymous variant in the zinc transporter SLC39A8 influences seven of the traits, including risk of schizophrenia (rs13107325: log-transformed odds ratio (log OR) = 0.15, P = 2 * 10(-12)) and Parkinson disease (log OR = -0.15, P = 1.6 * 10(-7)), among others. Second, we used these loci to identify traits that have multiple genetic causes in common. For example, variants associated with increased risk of schizophrenia also tended to be associated with increased risk of inflammatory bowel disease. Finally, we developed a method to identify pairs of traits that show evidence of a causal relationship. For example, we show evidence that increased body mass index causally increases triglyceride levels. PMID- 27182966 TI - Signaling from maize organ primordia via FASCIATED EAR3 regulates stem cell proliferation and yield traits. AB - Shoot apical meristems are stem cell niches that balance proliferation with the incorporation of daughter cells into organ primordia. This balance is maintained by CLAVATA-WUSCHEL feedback signaling between the stem cells at the tip of the meristem and the underlying organizing center. Signals that provide feedback from organ primordia to control the stem cell niche in plants have also been hypothesized, but their identities are unknown. Here we report FASCIATED EAR3 (FEA3), a leucine-rich-repeat receptor that functions in stem cell control and responds to a CLAVATA3/ESR-related (CLE) peptide expressed in organ primordia. We modeled our results to propose a regulatory system that transmits signals from differentiating cells in organ primordia back to the stem cell niche and that appears to function broadly in the plant kingdom. Furthermore, we demonstrate an application of this new signaling feedback, by showing that weak alleles of fea3 enhance hybrid maize yield traits. PMID- 27182967 TI - SAMD9 mutations cause a novel multisystem disorder, MIRAGE syndrome, and are associated with loss of chromosome 7. AB - Adrenal hypoplasia is a rare, life-threatening congenital disorder. Here we define a new form of syndromic adrenal hypoplasia, which we propose to term MIRAGE (myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy) syndrome. By exome sequencing and follow-up studies, we identified 11 patients with adrenal hypoplasia and common extra adrenal features harboring mutations in SAMD9. Expression of the wild-type SAMD9 protein, a facilitator of endosome fusion, caused mild growth restriction in cultured cells, whereas expression of mutants caused profound growth inhibition. Patient-derived fibroblasts had restricted growth, decreased plasma membrane EGFR expression, increased size of early endosomes, and intracellular accumulation of giant vesicles carrying a late endosome marker. Of interest, two patients developed myelodysplasitc syndrome (MDS) that was accompanied by loss of the chromosome 7 carrying the SAMD9 mutation. Considering the potent growth restricting activity of the SAMD9 mutants, the loss of chromosome 7 presumably occurred as an adaptation to the growth-restricting condition. PMID- 27182970 TI - Endohedral charge-transfer complex Ca@B37(-): stabilization of a B37(3-) borospherene trianion by metal-encapsulation. AB - Based on extensive first-principles theory calculations, we present the possibility of an endohedral charge-transfer complex, Cs Ca@B37(-) (), which contains a 3D aromatic fullerene-like Cs B37(3-) () trianion composed of interwoven boron double chains with twelve delocalized multicenter pi bonds (12 mc-2e pi, m = 5, 6) over a sigma skeleton, completing the Bn(q) borospherene family (q = n - 40) in the size range of n = 36-42. PMID- 27182971 TI - Laparoscopic Subcutaneous Transposition of a Pedicled Adrenal for ACTH Independent Bilateral Macronodular Adrenal Hyperplasia. AB - BACKGROUND AND PURPOSE: Bilateral adrenalectomy or unilateral adrenalectomy and contralateral partial adrenalectomy are indicated for the treatment of ACTH independent macronodular adrenal hyperplasia. Independent of the surgical procedure, the prognosis is poor. This article discusses a new treatment method and its efficacy for treating nodular adrenal hyperplasia. METHODS: We performed a retrospective review of the medical records of 12 patients operated on between January 2008 and October 2014 at the First Affiliated Hospital of Zhengzhou University. All patients were treated by laparoscopic subcutaneous transposition of a pedicled adrenal. We performed postoperative monitoring of patients, including clinical symptoms and 24-hour levels of serum-free and urinary-free cortisol. RESULTS: All 12 patients were pathologically confirmed to have nodular adrenal hyperplasia and were followed for an average of 45.5 months (range 24-60 months). The clinical symptoms of all patients disappeared, and the 24-hour plasma-free cortisol and urinary-free cortisol levels were within the normal range. CONCLUSIONS: Laparoscopic subcutaneous transposition of a pedicled adrenal is a new and effective method for treating bilateral macronodular adrenal hyperplasia and can achieve long-term remission of Cushing's syndrome. PMID- 27182968 TI - Divergent modes of clonal spread and intraperitoneal mixing in high-grade serous ovarian cancer. AB - We performed phylogenetic analysis of high-grade serous ovarian cancers (68 samples from seven patients), identifying constituent clones and quantifying their relative abundances at multiple intraperitoneal sites. Through whole-genome and single-nucleus sequencing, we identified evolutionary features including mutation loss, convergence of the structural genome and temporal activation of mutational processes that patterned clonal progression. We then determined the precise clonal mixtures comprising each tumor sample. The majority of sites were clonally pure or composed of clones from a single phylogenetic clade. However, each patient contained at least one site composed of polyphyletic clones. Five patients exhibited monoclonal and unidirectional seeding from the ovary to intraperitoneal sites, and two patients demonstrated polyclonal spread and reseeding. Our findings indicate that at least two distinct modes of intraperitoneal spread operate in clonal dissemination and highlight the distribution of migratory potential over clonal populations comprising high-grade serous ovarian cancers. PMID- 27182969 TI - A method to decipher pleiotropy by detecting underlying heterogeneity driven by hidden subgroups applied to autoimmune and neuropsychiatric diseases. AB - There is growing evidence of shared risk alleles for complex traits (pleiotropy), including autoimmune and neuropsychiatric diseases. This might be due to sharing among all individuals (whole-group pleiotropy) or a subset of individuals in a genetically heterogeneous cohort (subgroup heterogeneity). Here we describe the use of a well-powered statistic, BUHMBOX, to distinguish between those two situations using genotype data. We observed a shared genetic basis for 11 autoimmune diseases and type 1 diabetes (T1D; P < 1 * 10(-4)) and for 11 autoimmune diseases and rheumatoid arthritis (RA; P < 1 * 10(-3)). This sharing was not explained by subgroup heterogeneity (corrected PBUHMBOX > 0.2; 6,670 T1D cases and 7,279 RA cases). Genetic sharing between seronegative and seropostive RA (P < 1 * 10(-9)) had significant evidence of subgroup heterogeneity, suggesting a subgroup of seropositive-like cases within seronegative cases (PBUHMBOX = 0.008; 2,406 seronegative RA cases). We also observed a shared genetic basis for major depressive disorder (MDD) and schizophrenia (P < 1 * 10( 4)) that was not explained by subgroup heterogeneity (PBUHMBOX = 0.28; 9,238 MDD cases). PMID- 27182972 TI - Understanding the Relationships between Gender Inequitable Behaviours, Childhood Trauma and Socio-Economic Status in Single and Multiple Perpetrator Rape in Rural South Africa: Structural Equation Modelling. AB - BACKGROUND: Interventions to prevent rape perpetration must be designed to address its drivers. This paper seeks to extend understanding of drivers of single and multiple perpetrator rape (referred to here as SPR and MPR respectively) and the relationships between socio-economic status, childhood trauma, peer pressure, other masculine behaviours and rape. METHOD: 1370 young men aged 15 to 26 were interviewed as part of the randomised controlled trial evaluation of Stepping Stones in the rural Eastern Cape. We used multinomial to compare the characteristics of men who reported rape perpetration at baseline. We used structural equation modelling (SEM) to examine pathways to rape perpetration. RESULTS: 76.1% of young men had never raped, 10.0% had perpetrated SPR and 13.9% MPR. The factors associated with both MPR and SPR (compared to never having raped) were indicators of socio-economic status (SES), childhood trauma, sexual coercion by a woman, drug and alcohol use, peer pressure susceptibility, having had transactional sex, multiple sexual partners and being physically violent towards a partner. The SEM showed the relationship between SES and rape perpetration to be mediated by gender inequitable masculinity. It was complex as there was a direct path indicating that SES correlated with the masculinity variable directly such that men of higher SES had more gender inequitable masculinities, and indirect path mediated by peer pressure resistance indicated that the former pertained so long as men lacked peer pressure resistance. Having a higher SES conveyed greater resistance for some men. There was also a path mediated through childhood trauma, such that men of lower SES were more likely to have a higher childhood trauma exposure and this correlated with a higher likelihood of having the gender inequitable masculinity (with or without the mediating effect of peer pressure resistance). DISCUSSION: Both higher and lower socio-economic status were associated with raping. Prevention of rape perpetration must focus on changing men's gender ideals, entitlements and inequitable practices. Reducing poverty and adverse childhood experiences should also be of benefit. PMID- 27182974 TI - Biomechanical Effects of Novel Osteotomy Approaches on Mandibular Expansion: A Three-Dimensional Finite Element Analysis. AB - PURPOSE: Surgically assisted mandibular arch expansion has proved to be an effective treatment modality in alleviating constriction and crowding issues. However, only mandibular symphyseal distraction osteogenesis has been in favor for the purpose of mandibular arch expansion. In addition, no relevant study has compared the biomechanical response of different osteotomy designs on mandibular expansion. The present study evaluated the effect of different osteotomy approaches and modes of loading on the expansion of the adult mandible using biomechanics. MATERIALS AND METHODS: To address the research purpose, 9 finite element (FE) models, including 2 novel osteotomy designs, were simulated. Stress, strain, and displacement of crown, root, and bone were calculated and compared under different osteotomy approaches and loading conditions. RESULTS: The biomechanical response envisaged by the FE models in terms of displacement on the X axis was consistent from the anterior to posterior teeth with parasymphyseal step osteotomy and a hybrid mode of force application. In addition, the amount of displacement predicted by parasymphyseal step osteotomy with the hybrid mode was greater compared with that of the other models. CONCLUSIONS: The results of our study suggest parasymphyseal step osteotomy with the hybrid mode is a viable treatment option for true bony expansion in the adult mandible. PMID- 27182973 TI - Normative Values for Intertrial Variability of Motor Responses to Nerve Root and Transcranial Stimulation: A Condition for Follow-Up Studies in Individual Subjects. AB - OBJECTIVE: Intertrial variability (ITV) of motor responses to peripheral (CMAP) and transcranial (MEP) stimulation prevents their use in follow-up studies. Our purpose was to develop strategies to reduce and measure CMAP and MEP ITV to guide long-term monitoring of conduction slowing and conduction failure of peripheral and central motor pathway in the individual patient. METHODS: Maximal compound muscle action potentials to High Voltage Electrical Stimulation (HVES) of lumbo sacral nerve roots (r-CMAP) and activated, averaged motor evoked potentials (MEPs) to Transcranial Magnetic Stimulation (TMS) using double cone coil were recorded from 10 proximal and distal muscle districts of lower limbs. The procedure was repeated twice, 1-2 days apart, in 30 subjects, including healthy volunteers and clinically stable multiple sclerosis patients, using constant stimulating and recording sites and adopting a standardized procedure of voluntary activation. ITV for latency and area indexes and for the ratio between MEP and r-CMAP areas (a-Ratio) was expressed as Relative Intertrial Variation (RIV, 5th-95th percentile). As an inverse correlation between the size of area and ITV was found, raw ITV values were normalized as a function of area to make them comparable with one another. RESULTS: All RIV values for latencies were significantly below the optimum threshold of +/- 10%, with the exception of r CMAP latencies recorded from Vastus Lateralis muscle. RIVs for a-Ratio, the most important index of central conduction failure, ranged from a maximum of -25.3% to +32.2% (Vastus Medialis) to a minimum of -15.0% to + 17.4% (Flexor Hallucis Brevis). CONCLUSIONS: The described procedure represents an effort to lower as much as possible variability of motor responses in serial recording; the reported ITV normative values are the necessary premise to detect significant changes of motor conduction slowing and failure in the individual patient in follow-up studies. PMID- 27182975 TI - Correlating microbial community profiles with geochemical conditions in a watershed heavily contaminated by an antimony tailing pond. AB - Mining activities have introduced various pollutants to surrounding aquatic and terrestrial environments, causing adverse impacts to the environment. Indigenous microbial communities are responsible for the biogeochemical cycling of pollutants in diverse environments, indicating the potential for bioremediation of such pollutants. Antimony (Sb) has been extensively mined in China and Sb contamination in mining areas has been frequently encountered. To date, however, the microbial composition and structure in response to Sb contamination has remained overlooked. Sb and As frequently co-occur in sulfide-rich ores, and co contamination of Sb and As is observed in some mining areas. We characterized, for the first time, the microbial community profiles and their responses to Sb and As pollution from a watershed heavily contaminated by Sb tailing pond in Southwest China. The indigenous microbial communities were profiled by high throughput sequencing from 16 sediment samples (535,390 valid reads). The comprehensive geochemical data (specifically, physical-chemical properties and different Sb and As extraction fractions) were obtained from river water and sediments at different depths as well. Canonical correspondence analysis (CCA) demonstrated that a suite of in situ geochemical and physical factors significantly structured the overall microbial community compositions. Further, we found significant correlations between individual phylotypes (bacterial genera) and the geochemical fractions of Sb and As by Spearman rank correlation. A number of taxonomic groups were positively correlated with the Sb and As extractable fractions and various Sb and As species in sediment, suggesting potential roles of these phylotypes in Sb biogeochemical cycling. PMID- 27182976 TI - Enantioselective degradation of amphetamine-like environmental micropollutants (amphetamine, methamphetamine, MDMA and MDA) in urban water. AB - This paper aims to understand enantioselective transformation of amphetamine, methamphetamine, MDMA (3,4-methylenedioxy-methamphetamine) and MDA (3,4 methylenedioxyamphetamine) during wastewater treatment and in receiving waters. In order to undertake a comprehensive evaluation of the processes occurring, stereoselective transformation of amphetamine-like compounds was studied, for the first time, in controlled laboratory experiments: receiving water and activated sludge simulating microcosm systems. The results demonstrated that stereoselective degradation, via microbial metabolic processes favouring S-(+) enantiomer, occurred in all studied amphetamine-based compounds in activated sludge simulating microcosms. R-(-)-enantiomers were not degraded (or their degradation was limited) which proves their more recalcitrant nature. Out of all four amphetamine-like compounds studied, amphetamine was the most susceptible to biodegradation. It was followed by MDMA and methamphetamine. Photochemical processes facilitated degradation of MDMA and methamphetamine but they were not, as expected, stereoselective. Preferential biodegradation of S-(+) methamphetamine led to the formation of S-(+)-amphetamine. Racemic MDMA was stereoselectively biodegraded by activated sludge which led to its enrichment with R-(-)-enantiomer and formation of S-(+)-MDA. Interestingly, there was only mild stereoselectivity observed during MDMA degradation in rivers. This might be due to different microbial communities utilised during activated sludge treatment and those present in the environment. Kinetic studies confirmed the recalcitrant nature of MDMA. PMID- 27182977 TI - Risk of pesticide exposure for reptile species in the European Union. AB - Environmental pollution has an especially high impact on wildlife. This is especially the case in industrialized countries. Although, many species within the European Union benefit from protection by the Habitats Directive, no special consideration is given to possible detrimental effects of pesticides. This is in particular remarkable as negative effects, which may lead to a regional diversity loss, have already been identified in laboratory and mesocosm studies. We conducted a pesticide exposure risk evaluation for all European reptile species with sufficient literature data on the considered biological and ecological aspects and occurrence data within agricultural areas with regular pesticide applications (102 out of 141). By using three evaluation factors - (i) pesticide exposure, (ii) physiology and (iii) life history - a taxon-specific pesticide exposure risk factor (ERF) was created. The results suggest that about half of all evaluated species, and thus at least 1/3 of all European species exhibited a high exposure risk. At the same time, two of them (Mauremys leprosa and Testudo graeca) are globally classified as threatened with extinction in the IUCN Red List of Threatened Species. Variation regarding species occurrence in exposed landscapes between pesticide admission zones within the EU is rather large. This variation is mainly caused by differing land use and species abundances between zones. At the taxonomic level, significant differences in exposure risk can be observed between threatened and non-threatened species, which can be explained by the formers remote distribution areas. Lizards display the highest sensitivity toward pesticides, although no differences in overall ERFs can be observed between taxonomic groups. By identifying species at above-average risk to pesticide exposure, species-based risk evaluations can improve conservation actions for reptiles from cultivated landscapes. PMID- 27182978 TI - Alterations in juvenile diploid and triploid African catfish skin gelatin yield and amino acid composition: Effects of chlorpyrifos and butachlor exposures. AB - Skin is a major by-product of the fisheries and aquaculture industries and is a valuable source of gelatin. This study examined the effect of triploidization on gelatin yield and proximate composition of the skin of African catfish (Clarias gariepinus). We further investigated the effects of two commonly used pesticides, chlorpyrifos (CPF) and butachlor (BUC), on the skin gelatin yield and amino acid composition in juvenile full-sibling diploid and triploid African catfish. In two separate experiments, diploid and triploid C. gariepinus were exposed for 21 days to graded CPF [mean measured: 10, 16, or 31 MUg/L] or BUC concentrations [Mean measured: 22, 44, or 60 MUg/L]. No differences in skin gelatin yield, amino acid or proximate compositions were observed between diploid and triploid control groups. None of the pesticide treatments affected the measured parameters in diploid fish. In triploids, however, gelatin yield was affected by CPF treatments while amino acid composition remained unchanged. Butachlor treatments did not alter any of the measured variables in triploid fish. To our knowledge, this study is the first to investigate changes in the skin gelatin yield and amino acid composition in any animal as a response to polyploidization and/or contaminant exposure. PMID- 27182979 TI - Metal/metalloid (As, Cd and Zn) bioaccumulation in the earthworm Eisenia andrei under different scenarios of climate change. AB - This study aimed at assessing the effects of global warming (increasing air temperature and decreasing soil moisture content) on the bioaccumulation kinetics of As, Cd and Zn in the earthworm Eisenia andrei in two polluted soils (mine tailing and watercourse soil). Earthworms were exposed for up to 21 d under four climate conditions: 20 degrees C + 50% soil water holding capacity (WHC) (standard conditions), 20 degrees C + 30% WHC, 25 degrees C + 50% WHC and 25 degrees C + 30% WHC. Porewater metal/metalloid availability did not change in the mine tailing soil after the incubation period under the different climate conditions tested. However, in the watercourse soil, porewater Cd concentrations decreased from ~63 to ~32-41 MUg L(-1) after 21 d and Zn concentrations from ~3761 to ~1613-2170 MUg L(-1), especially at 20 degrees C and 50% WHC. In both soils, As and Zn showed similar bioaccumulation patterns in the earthworms, without major differences among climate conditions. Earthworm concentrations peaked after 1-3 d of exposure (in MUg g(-1) dry weight: As~32.5-108, Zn~704 1172) and then remained constant (typical pattern of essential elements even for As). For Cd the bioaccumulation pattern changed when changing the climate conditions. Under standard conditions, earthworm Cd concentrations increased to ~12.6-18.5 MUg g(-1) dry weight without reaching equilibrium (typical pattern of non-essential elements). However when increasing temperature and/or decreasing soil moisture content the bioaccumulation pattern changed towards that more typical of essential elements due to increased Cd elimination rates (from ~0.11 to ~0.24-1.27 d(-1) in the mine tailing soil, from ~0.07 to ~0.11-0.35 d(-1) in the watercourse soil) and faster achievement of a steady state. This study shows that metal/metalloid bioaccumulation pattern in earthworms may change dependent on climate conditions. PMID- 27182980 TI - Developing a Triple Transgenic Cell Line for High-Efficiency Porcine Reproductive and Respiratory Syndrome Virus Infection. AB - Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most devastating pathogens in the swine industry worldwide. Due to the lack of robust cell lines and small animal models, the pathogenesis of PRRSV infection and mechanism for protective vaccination are still not yet well understood. To obtain useful cell lines, several groups have attempted to construct different transgenic cell lines with three PRRSV receptors: CD163, CD169, and CD151. The results showed that CD163 is essential for PRRSV entry into target cells and replication, and both CD169 and CD151 play key roles during PRRSV infection. However, their interplay and combined effect remains unclear. In this study, we generated transgenic BHK-21 derived cell lines co-expressing different combinations of the three receptors, which were transfected with CD163 alone, or the combination of CD163 and CD169, or the combination of CD163 and CD151, or the combination of CD163, CD169, and CD151 using the PiggyBac transposon system. Our results showed that the synergistic interaction among the three receptors was important to improve the susceptibility of cells during PRRSV infection. Through a series of comparable analyses, we confirmed that the cell line co-expressing triple receptors sustained viral infection and replication, and was superior to the current cell platform used for the PRRSV study, MARC-145 cells. Moreover, we found that PRRSV infection of the transgenic cell lines could trigger IFN stimulated gene responses similar to those of porcine alveolar macrophages and MARC-145 cells. In summary, we developed a stable transgenic cell line susceptible to PRRSV, which may not only provide a useful tool for virus propagation, vaccine development, and pathogenesis studies, but also establish the foundation for small animal model development. PMID- 27182981 TI - New formulas for mixing test to discriminate between lupus anticoagulant and acquired hemophilia A. AB - INTRODUCTION: Lupus anticoagulant (LA) is an antibody that interferes with in vitro coagulation reactions. The mixing test is considered useful for LA diagnosis and is also recommended to differentiate between acquired hemophilia A (AHA) and factor deficiency. However, there has been little study to differentiate between LA and AHA. Our aims are to investigate whether we can differentiate LA and AHA by the mixing test and to establish new formulas for the mixing test to differentiate these samples clearly. MATERIALS AND METHODS: We examined 27 LA-positive, 29 coagulation factor deficient, 24 unfractionated heparin and 48 AHA samples. Index of circulating anticoagulant (ICA) values, calculated from the clotting times without incubation and after 2h incubation, were defined as ICA immediate (ICAi) and ICA delayed (ICAd) respectively. ICAd/ICAi and ICAd-ICAi were also calculated to compare the sensitivity and specificity. RESULTS: ICAd/ICAi and ICAd-ICAi for AHA samples were significantly higher than those of the other sample groups. The sensitivities to AHA in ICAi, ICAd, ICAd/ICAi and ICAd-ICAi were 66.7%, 81.3%, 93.8% and 91.7% respectively, while the specificities for AHA were 45.0%, 66.3%, 85.0% and 98.8% respectively. ICAd/ICAi and ICAd-ICAi showed high sensitivity and specificity. CONCLUSIONS: ICAd/ICAi and ICAd-ICAi were useful for LA and AHA diagnosis, because these could differentiate between LA and AHA samples. These new formulas can contribute to the rapid diagnosis and treatment of LA and AHA. PMID- 27182982 TI - Sunshine, Sea, and Season of Birth: MS Incidence in Wales. AB - Maternal sun exposure in gestation and throughout the lifetime is necessary for vitamin D synthesis, and living near the sea is a population level index of seafood consumption. The aim of this study was to estimate the incidence rate of multiple sclerosis (MS) in Wales and examine its association with sun exposure, coastal living, and latitude. The study used a database of MS hospital visits and admissions in Wales between 2002 and 2013. For the 1,909 lower layer super output areas (LSOAs) in Wales, coastal status, population, longitude/latitude, and average sunshine hours per day were obtained. Age-specific and age-standardised MS incidence were calculated and modelled using Poisson regression. The distribution of births by month was compared between MS cases and the combined England and Wales population. There were 3,557 new MS cases between 2002 and 2013, with an average annual incidence of 8.14 (95% CI: 7.69-8.59) among males and 12.97 (95% CI: 12.44-13.50) among females per 100,000 population. The female to-male ratio was 1.86:1. For both sexes combined, the average annual incidence rate was 9.10 (95% CI: 8.80-9.40). All figures are age-standardized to the 1976 European standard population. Compared to the combined England and Wales population, more people with MS were born in April, observed-to-expected ratio: 1.21 (95% CI: 1.08-1.36). MS incidence varied directly with latitude and inversely with sunshine hours. Proximity to the coast was associated with lower MS incidence only in easterly areas. This study shows that MS incidence rate in Wales is comparable to the rate in Scotland and is associated with environmental factors that probably represent levels of vitamin D. PMID- 27182984 TI - Skin Necrosis after Subcutaneous Diclofenac Administration: A Case Report. PMID- 27182983 TI - Divergent Development of Hexaploid Triticale by a Wheat - Rye -Psathyrostachys huashanica Trigeneric Hybrid Method. AB - Hexaploid triticale is an important forage crop and a promising energy plant. Some forms were previously reported for developing the hexaploid triticale, such as crossing tetraploid wheat or hexaploid wheat with rye, crossing hexaploid triticale and/or hexaploid wheat with octoploid triticale, and spontaneously appearing in the selfed progenies of octoploid triticale. In the present study, we developed an effective method for production of diverse types of hexaploid triticale via wheat-rye-Psathyrostachys huashanica trigeneric hybrid. Genomic in situ hybridization (GISH) and fluorescence in situ hybridization (FISH) karyotyping revealed that D genome chromosomes were completely eliminated and the whole A, B, and R genome chromosomes were retained in three lines. More interestingly, the composite genome of the line K14-489-2 consisted of complete A and B genomes and chromosomes 1D, 2R, 3R, 4R, 5R, 6R, and 7R, that of line K14 491-2 was 12 A-genome (1A-6A), 14 B-genome (1B-7B), 12 R-genome (1R-3R, 5R-7R), and chromosomes 1D and 3D, and that of the line K14-547-1 had 26A/B and 14R chromosomes, plus one pair of centric 6BL/2DS translocations. This finding implies that some of D genome chromosomes can be spontaneously and stably incorporated into the hexaploid triticale. Additionally, a variety of high molecular-weight glutenin subunits (HMW-GS) compositions were detected in the six hexaploid triticale lines, respectively. Besides, compared with its recurrent triticale parent Zhongsi828, these lines showed high level of resistance to stripe rust (Puccinia striiformis f. sp. tritici, Pst) pathogens prevalent in China, including V26/Gui 22. These new hexaploid triticales not only enhanced diversification of triticale but also could be utilized as valuable germplasm for wheat improvement. PMID- 27182985 TI - Embargo on Lion Hunting Trophies from West Africa: An Effective Measure or a Threat to Lion Conservation? AB - The W-Arly-Pendjari (WAP) ecosystem, shared among Benin, Burkina Faso and Niger, represents the last lion stronghold of West Africa. To assess the impact of trophy hunting on lion populations in hunting areas of the WAP, we analyzed trends in harvest rates from 1999 to 2014. We also investigated whether the hunting areas with higher initial hunting intensity experienced steeper declines in lion harvest between 1999 and 2014, and whether lion densities in hunting areas were lower than in national parks. Lion harvest rate remained overall constant in the WAP. At initial hunting intensities below 1.5 lions/1000km2, most hunting areas experienced an increase in lion harvest rate, although that increase was of lower magnitude for hunting areas with higher initial hunting intensity. The proportion of hunting areas that experienced a decline in lion harvest rate increased at initial hunting intensities above 1.5 lions/1000km2. In 2014, the lion population of the WAP was estimated with a spoor count at 418 (230 648) adults and sub-adult individuals, comparable to the 311 (123-498) individuals estimated in the previous 2012 spoor survey. We found no significant lion spoor density differences between national parks and hunting areas. Hunting areas with higher mean harvest rates did not have lower lion densities. The ratio of large adult males, females and sub-adults was similar between the national parks and the hunting areas. These results suggested that the lion population was not significantly affected by hunting in the WAP. We concluded that a quota of 1 lion/1000km2 would be sustainable for the WAP. Based on our results, an import embargo on lion trophies from the WAP would not be justified. It could ruin the incentive of local actors to conserve lions in hunting areas, and lead to a drastic reduction of lion range in West Africa. PMID- 27182987 TI - Physical Activity, Fitness, Cognitive Function, and Academic Achievement in Children: A Systematic Review. PMID- 27182988 TI - Outcomes of patients with chronic lymphocytic leukemia treated with first-line idelalisib plus rituximab after cessation of treatment for toxicity. AB - BACKGROUND: More active therapies are needed for older and unfit patients with chronic lymphocytic leukemia (CLL) who are not eligible for chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab. The phosphyotidylinositol-3 kinase delta inhibitor idelalisib is effective in patients with treatment-naive and relapsed/refractory CLL as monotherapy and in combination with rituximab, but it can be associated with treatment-limiting adverse events, particularly diarrhea/colitis. The outcomes for patients who cease treatment for adverse events have not been previously described. METHODS: The authors analyzed long term follow-up data from 40 treatment-naive patients aged >=65 years who received treatment at The University of Texas MD Anderson Cancer Center on a phase 2 study of idelalisib plus rituximab for CLL. RESULTS: In patients who permanently ceased treatment because of toxicity, the time to subsequent disease progression was analyzed according to baseline characteristics. Fifteen patients permanently ceased therapy (PCT) because of toxicity (PCTTOX ), most commonly diarrhea/colitis (n = 7), at a median of 11 months after commencing treatment. PCTTOX was associated with a higher risk of subsequent disease progression (hazard ratio, 6.61; 95% confidence interval, 1.77-16.15) relative to that observed in patients who remained on therapy. Ten patients subsequently progressed, and 7 required salvage therapy; 5 patients remained progression-free at a median of 23.3 months (range, 8.5-28.6 months). Patients who were positive for zeta-associated protein-70 had more rapid disease progression after treatment cessation (P = .048). There were no CLL-related deaths. CONCLUSIONS: PCTTOX is the major determinant of PFS in patients who receive first-line idelalisib-based treatment. However, a subgroup of patients with favorable biologic characteristics has prolonged PFS, even after PCTTOX . The absence of CLL-related deaths indicates that salvage treatment is generally successful after PCTTOX . Cancer 2016;122:2505-11. (c) 2016 American Cancer Society. PMID- 27182986 TI - Physical Activity, Fitness, Cognitive Function, and Academic Achievement in Children: A Systematic Review. AB - BACKGROUND: The relationship among physical activity (PA), fitness, cognitive function, and academic achievement in children is receiving considerable attention. The utility of PA to improve cognition and academic achievement is promising but uncertain; thus, this position stand will provide clarity from the available science. OBJECTIVE: The purpose of this study was to answer the following questions: 1) among children age 5-13 yr, do PA and physical fitness influence cognition, learning, brain structure, and brain function? 2) Among children age 5-13 yr, do PA, physical education (PE), and sports programs influence standardized achievement test performance and concentration/attention? STUDY ELIGIBILITY CRITERIA: This study used primary source articles published in English in peer-reviewed journals. Articles that presented data on, PA, fitness, or PE/sport participation and cognition, learning, brain function/structure, academic achievement, or concentration/attention were included. DATA SOURCES: Two separate searches were performed to identify studies that focused on 1) cognition, learning, brain structure, and brain function and 2) standardized achievement test performance and concentration/attention. PubMed, ERIC, PsychInfo, SportDiscus, Scopus, Web of Science, Academic Search Premier, and Embase were searched (January 1990-September 2014) for studies that met inclusion criteria. Sixty-four studies met inclusion criteria for the first search (cognition/learning/brain), and 73 studies met inclusion criteria for the second search (academic achievement/concentration). STUDY APPRAISAL AND SYNTHESIS METHODS: Articles were grouped by study design as cross-sectional, longitudinal, acute, or intervention trials. Considerable heterogeneity existed for several important study parameters; therefore, results were synthesized and presented by study design. RESULTS: A majority of the research supports the view that physical fitness, single bouts of PA, and PA interventions benefit children's cognitive functioning. Limited evidence was available concerning the effects of PA on learning, with only one cross-sectional study meeting the inclusion criteria. Evidence indicates that PA has a relationship to areas of the brain that support complex cognitive processes during laboratory tasks. Although favorable results have been obtained from cross-sectional and longitudinal studies related to academic achievement, the results obtained from controlled experiments evaluating the benefits of PA on academic performance are mixed, and additional, well designed studies are needed. LIMITATIONS: Limitations in evidence meeting inclusion criteria for this review include lack of randomized controlled trials, limited studies that are adequately powered, lack of information on participant characteristics, failure to blind for outcome measures, proximity of PA to measurement outcomes, and lack of accountability for known confounders. Therefore, many studies were ranked as high risk for bias because of multiple design limitations. CONCLUSIONS: The present systematic review found evidence to suggest that there are positive associations among PA, fitness, cognition, and academic achievement. However, the findings are inconsistent, and the effects of numerous elements of PA on cognition remain to be explored, such as type, amount, frequency, and timing. Many questions remain regarding how to best incorporate PA within schools, such as activity breaks versus active lessons in relation to improved academic achievement. Regardless, the literature suggests no indication that increases in PA negatively affect cognition or academic achievement and PA is important for growth and development and general health. On the basis of the evidence available, the authors concluded that PA has a positive influence on cognition as well as brain structure and function; however, more research is necessary to determine mechanisms and long-term effect as well as strategies to translate laboratory findings to the school environment. Therefore, the evidence category rating is B. The literature suggests that PA and PE have a neutral effect on academic achievement. Thus, because of the limitations in the literature and the current information available, the evidence category rating for academic achievement is C. PMID- 27182990 TI - Diabetes during Pregnancy in Low- and Middle-Income Countries. AB - Objective Our objective was to review the literature in relationship to diabetes in pregnancy in low and middle income countries. Study Design We reviewed the English language literature related to diabetes and obesity during pregnancy in low and middle income countries published over the last 20 years. Results The global prevalence of diabetes mellitus is an estimated 8% with approximately 380 million adults with this condition worldwide. Ninety percent of diabetes in adults occurs in low- and middle-income countries (LMIC). However, diabetes is highly correlated with obesity and the highest diabetes rates occur in countries with the highest obesity rates. Hyperglycemia complicates 17% of pregnancies, including women with diagnosed and undiagnosed types 1 and 2 diabetes, and gestational diabetes mellitus (GDM). In many LMIC, as pregnancy becomes more common in wealthier, older, and more obese women, pregnancies complicated by pregestational diabetes and GDM will increase. Approximately half of women with hyperglycemia in pregnancy are undiagnosed. Even with diagnosis, because of the numerous tests and criteria for abnormal glucose levels used worldwide, the prevalence of hyperglycemia in pregnancy can only be approximated. Moving forward, a single set of tests and diagnostic criteria is recommended. Although the risk factors and pregnancy outcomes for pregestational diabetes and GDM are similar in LMIC to wealthier countries, they appear to occur more commonly, and with worse outcomes because of poor access to care. In the poorest areas, inadequate antenatal and general medical care increase the difficulty in managing diabetes and its complications for women and newborns. Conclusion As obesity among women increases, diabetes in pregnancy is becoming increasingly common in LMIC. Because of lack of resources and trained personnel, and other priorities related to reducing maternal, fetal, and neonatal mortality, diagnosing and providing care to women with diabetes in pregnancy is not high on the priority lists in many LMIC. PMID- 27182989 TI - Expression Regulation of Polycistronic lee3 Genes of Enterohaemorrhagic Escherichia coli. AB - Enterohaemorrhagic Escherichia coli O157:H7 (EHEC) carries a pathogenic island LEE that is consisted mainly of five polycistronic operons. In the lee3 operon, mpc is the first gene and has been reported to down regulate the type-3 secretion system of EHEC when its gene product is over-expressed. Furthermore, mpc has been suggested to have a regulation function via translation but the mechanism remains unclear. To clarify this hypothesis, we dissected the polycistron and examined the translated products. We conclude that translation of mpc detrimentally governs the translation of the second gene, escV, which in turn affects the translation of the third gene, escN. Then sequentially, escN affects the expression of the downstream genes. Furthermore, we located a critical cis element within the mpc open-reading frame that plays a negative role in the translation-dependent regulation of lee3. Using qRT-PCR, we found that the amount of mpc RNA transcript present in EHEC was relatively limited when compared to any other genes within lee3. Taken together, when the transcription of LEE is activated, expression of mpc is tightly controlled by a restriction of the RNA transcript of mpc, translation of which is then critical for the efficient production of the operon's downstream gene products. PMID- 27182991 TI - A New IVH Scoring System Based on Laterality Enhances Prediction of Neurodevelopmental Outcomes at 3 Years Age in Premature Infants. AB - Objective To compare the new intraventricular hemorrhage (IVH) Abdi score to the Papile grading system of IVH for prediction of composite outcome of death or neurodevelopmental impairment (NDI). Methods In a cohort study, all preterm infants with IVH who were born <=1,250 g and/or <= 28 weeks of gestation at birth were prospectively followed up in our neonatal follow-up clinic. All cranial ultrasounds of the included infants were reviewed by neuroradiologists who were blinded to the clinical data and neurodevelopmental outcomes. Cranial ultrasounds were graded according to the Papile scoring system and by calculation of the Abdi score. Results A total of 183 preterm infants met inclusion and exclusion criteria. Of these, 80 (44%) had the composite primary outcome of death or NDI (51 died, 29 survived with NDI). The area under receiver operating characteristic curve for predicting death or NDI was 0.87 (95% confidence interval [CI]: 0.81 0.93) for Abdi score and 0.85 (95% CI: 0.79-0.91) for Papile grading (p = 0.04). Abdi scores had higher specificity than Papile grade II at Abdi score 5 (63.9 vs. 39.2%; p < 0.001) and Abdi score 6 (73.2 vs. 39.2%; p < 0.001). Conclusion Abdi scores seem to be more specific than Papile grading system in predicting death or NDI by 3 years' corrected age. PMID- 27182993 TI - Birth Weight by Gestational Age for 76,710 Twins Born in the United States as a Result of In Vitro Fertilization: 2006 to 2010. AB - Objective The objective of this study was to establish twin-specific birth weight percentiles by gestational age using U.S. twin births resulting from in vitro fertilization (IVF). Study Design A retrospective analysis of birth weight by completed weeks of gestation for 76,710 twin IVF births reported to the Society for Assisted Reproductive Technologies from 2006 to 2010. Mean and median birth weights and 3rd, 5th, 10th, 25th, 50th, 75th, 90th, and 97th percentiles were calculated by completed week of gestation and infant sex. Results IVF twin birth weight accelerates until term and then declines. The deceleration in twin birth weight occurs at 39 completed weeks of gestation for larger twins, those at or above the 50th percentile in weight. For smaller twins, the growth deceleration occurs earlier, at 38 weeks of gestation. IVF female and male twin birth weights for gestational age were similar to all IVF twins, showing similar decelerations near term. Conclusion Using U.S. IVF twin-specific growth charts, with known date of conception, twins demonstrate a deceleration in birth weight near term. Larger twins demonstrate a deceleration in birth weight by 39 completed weeks of gestation; smaller twins show a deceleration at 38 weeks. These data may assist in the clinical management of twins near term. PMID- 27182992 TI - Intravenous Acetaminophen versus Morphine for Analgesia in Labor: A Randomized Trial. AB - Objective To compare the effectiveness of intravenous acetaminophen with that of morphine in reducing pain in the first stage of labor. Methods An open-label, randomized controlled trial of women >= 34 weeks gestation in the first stage of labor, assigned to either intravenous acetaminophen or morphine. The primary outcome was improved analgesia measured by difference of visual analog scale (VAS) score at 120 minutes from baseline. Secondary outcomes were request for rescue analgesia, maternal side effects, and fetal heart rate changes. Statistical analyses performed were chi-square, Student's t-test, and Kaplan Meier survival analysis. Results Of 40 women randomized, 18 received acetaminophen (2 did not receive study drug), and 20 received morphine. Because of difficulties in recruitment, the sample size of 88 was not achieved. The primary outcome was similar between groups (p = 0.53). Within 120 minutes of initial treatment, more women receiving intravenous acetaminophen required rescue analgesia (acetaminophen: 52.9% vs. morphine: 17.6%, p < 0.01). Maternal and fetal side effects were similar between groups. Conclusion There was no difference in VAS scores between groups. However, as half of women receiving intravenous acetaminophen required rescue analgesia within 120 minutes of treatment, intravenous acetaminophen may be less effective for analgesia in early labor compared with intravenous morphine. PMID- 27182994 TI - Effect of Volume Guarantee in Preterm Infants on High-Frequency Oscillatory Ventilation: A Pilot Study. AB - Objectives Although adding volume guarantee (VG) to conventional ventilation has been a well-established respiratory management for preterm infants, the evidence of VG combined with high-frequency oscillatory ventilation (HFOV) has not been studied well. The aim of this study was to investigate the effect of VG added to HFOV on respiratory and other physiological parameters. Methods We conducted a pilot study in extremely low-birth-weight infants ventilated with HFOV + VG with stable pulmonary status after 28 days of age. VG was applied for 6 hours and removed for the following 6 hours, and data were collected during these 12 hours. Results Six neonates were included in this study (gestational age: 22w5d-23w6d, birthweight: 424-584 g). High-frequency expired tidal volume per weight and amplitude were similar between periods with and without VG. Fluctuation of SpO2, but not heart rate, was significantly smaller when babies were ventilated with VG than without VG. Fluctuation of minute volume and carbon dioxide diffusion coefficient significantly increased after VG removal. The proportion of time with SpO2 < 80% was decreased by VG overall, especially in three cases. Conclusion This pilot study suggests VG combined with HFOV attenuates fluctuation of SpO2 and CO2 clearance, which may prevent hypoxemia and hypocapnia. PMID- 27182995 TI - Comparison of Passive and Servo-Controlled Active Cooling for Infants with Hypoxic-Ischemic Encephalopathy during Neonatal Transfers. AB - Objective The recent availability of servo-controlled cooling equipment on transport makes it possible to commence active cooling at the referral unit for infants with hypoxic-ischemic encephalopathy. This study aimed to compare the temperature and transfer variables in passively and actively cooled babies. Study Design This is a retrospective cohort study comparing two groups-passively cooled (July 2011 to August 2012) versus actively cooled group (September 2012 to June 2013), following introduction of active hypothermia using servo-controlled cooling mattress by the London Neonatal Transfer Service (NTS). Results Seventy six infants were passively cooled and 69 were actively cooled. There was a significant difference between the temperatures of the two groups at each point in the transfer episode: on arrival of NTS, during stabilization, during transfer, and at the receiving hospital. Median time to achieve target temperature was 30 (95% confidence interval [CI]: 23-37) minutes in actively cooled, significantly shorter in comparison to 130 (95% CI: 83-177) minutes in passively cooled babies. Of the 69 newborns, 62 (90%) had temperature within target range at receiving center in actively cooled group as compared with 30/76 (40%) in passively cooled group. Conclusion The use of active cooling during neonatal transfer achieves target temperature in a shorter period and maintains better temperature stability. PMID- 27182996 TI - Does Red Blood Cell Transfusion-Related Acute Lung Injury Occur in Premature Infants? A Retrospective Cohort Analysis. AB - Objective The objective of this study was to determine whether packed red blood cell (pRBC) transfusions in extremely low birth weight (ELBW) infants were associated with acute respiratory decompensation (ARD). Study Design Retrospective chart review of ELBW infant pRBC transfusions analyzed for meeting ARD criteria during the 6 hours post-pRBC transfusion was compared with the pretransfusion baseline period. A control period subdivided into similar pre- and postintervals was also assessed for each infant. ARD was defined as >= 1 of the following: (1) >= 10% increase in fraction of inspired oxygen from highest baseline, (2) >= 2 cm H2O increase from highest baseline in mean airway pressure, or (3) escalation in mode of respiratory support. Results A total of 238 pRBC transfusions occurred in 36 ELBW infants during 2012. Complete data for both the transfusion and control time periods existed for 110 pRBC transfusions (25 infants) and were included for analysis. The frequency of ARD was 15.5 and 18.2% (odds ratio, 1.25; p = 0.70) in the control and transfusion time periods, respectively. Conclusion pRBC transfusions in ELBW neonates are not associated with statistically significant rates of ARD compared with nontransfusion control time periods. PMID- 27182997 TI - Variability in Apgar Score Assignment among Clinicians: Role of a Simple Clarification. AB - Objective We aimed to evaluate variability in Apgar score (AS) assignment among health care providers (HCPs) and to evaluate whether a simple clarification improves accuracy and consistency of AS assignment. Study Design An electronic questionnaire survey was provided to pediatric residents, nurse practitioners, neonatal fellows, and faculty in level III neonatal intensive care unit and major academic centers in the United State to assign AS for three clinical scenarios. Next, we provided a simple clarification on various components of AS. After review of clarification, responders were asked to provide AS for the same scenarios. We also sought the opinion of responders on the subjectivity of five components of AS. Results A total of 107 responses were collected. Correct assignment before and after clarification improved significantly: heart rate (78 vs. 90%, p = 0.02), reflex (63 vs.75%, p = 0.06), and breathing (82 vs. 96%, p = 0.003). Correct scoring for color and tone were 86 and 67%, respectively. Interobserver agreement improved significantly after clarification. Conclusion There was variability among HCPs for AS assignment, with improvement in correct response as well as consistency after a simple clarification. Availability of this clarification, along with the AS table in delivery room, will improve the correct assignment and consistency of AS for high-risk infants. PMID- 27182998 TI - Evaluating the Sensitivity of Electronic Fetal Monitoring Patterns for the Prediction of Intraventricular Hemorrhage. AB - Objective We evaluated electronic fetal (heart rate) monitoring (EFM) patterns among very preterm infants with and without intraventricular hemorrhage (IVH) to evaluate the test characteristics of EFM for the prediction of IVH. Study Design We performed a case-control study of preterm infants born <= 30 weeks' gestation over a 6-year period. We evaluated differences in EFM patterns between those (cases) with and without IVH (controls). The relative odds ratio of observing differences in EFM patterns between cases and controls was calculated. Regression models were adjusted based on confounding variables. The sensitivity, specificity, and positive and negative predictive values of EFM characteristics were evaluated for the diagnosis of IVH. Results Total 79 very preterm infants underwent cranial ultrasound, 24 of whom had IVH. Infants with IVH were more likely to be males and delivered at earlier gestational ages. Moderate variability was seen in all infants with normal cranial ultrasounds and 83% of infants with IVH. Minimal variability has a sensitivity of 17% in the prediction of IVH. Conclusion While minimal variability was observed more frequently in fetuses that developed IVH, it is poorly predictive of IVH. EFM patterns are not discriminating in identifying very preterm infants at risk for developing IVH. PMID- 27182999 TI - Viral Infections in Neonates with Suspected Late-Onset Bacterial Sepsis-A Prospective Cohort Study. AB - Objective The aim of our study was to evaluate the occurrence of viral infections in infants with suspected late-onset bacterial sepsis in a neonatal intensive care unit. Methods In a prospective study, infants with suspected late-onset bacterial sepsis underwent viral testing alongside routine blood culture sampling. Using a multiplex reverse transcription-polymerase chain reaction enzyme-linked immunosorbent assay, nasopharyngeal aspirates were analyzed for adenovirus, respiratory syncytial virus (RSV), influenza virus A and B, H1N1 virus, parainfluenza virus 1 to 4, metapneumovirus, coronavirus, and picornavirus. Stools were examined for adenovirus, rotavirus, norovirus, and enterovirus. Results Between August 2010 and March 2014, data of 88 infants with 137 episodes of suspected late-onset bacterial sepsis were analyzed. Six infants were diagnosed with a respiratory viral infection (2 * RSV, 4 * picornavirus). Blood culture-proven bacterial sepsis was detected in 15 infants. Neither viral bacterial coinfections nor polymerase chain reaction positive stool samples were found. Conclusion Respiratory viruses can be detected in a considerable number of neonates with suspected late-onset bacterial sepsis. In contrast, gastrointestinal viral or enterovirus infections appear uncommon in such cases. PMID- 27183000 TI - Birth Tourism and Neonatal Intensive Care: A Children's Hospital Experience. AB - Objective The aim of this article is to examine characteristics of birth tourism (BT) neonates admitted to a neonatal intensive care unit (NICU). Methods This was a retrospective review over 3 years; BT cases were identified, and relevant perinatal, medical, social, and financial data were collected and compared with 100 randomly selected non-birth tourism neonates. Results A total of 46 BT neonates were identified. They were more likely to be born to older women (34 vs. 29 years; p < 0.001), via cesarean delivery (72 vs. 48%; p = 0.007), and at a referral facility (80 vs. 32%; p < 0.001). BT group had longer hospital stay (15 vs. 7 days; p = 0.02), more surgical intervention (50 vs. 21%; p < 0.001), and higher hospital charges (median $287,501 vs. $103,105; p = 0.003). One-third of BT neonates were enrolled in public health insurance program and four BT neonates (10%) were placed for adoption. Conclusion Families of BT neonates admitted to the NICU face significant challenges. Larger studies are needed to better define impacts on families, health care system, and society. PMID- 27183002 TI - The impact of various protective tools on the dose reduction in the eye lens in an interventional cardiology-clinical study. AB - The aim of the study was to check, in clinical practice, the potential for the dose reduction of lead eyewear and a ceiling-suspended shield used to protect the eye lens of physicians working in interventional cardiology. To this end, for the lead eyewear, the dose reduction factors were derived to correct the readings from a dosimeter used routinely outside the glasses. Four types of lead eyewear with attached loose thermoluminescent dosimeters and EYE-D dosimeters were worn by physicians in two clinical centres, for two-month periods, during coronary angiography (CA), percutaneous coronary intervention (PCI), and pacemaker procedures. In order to analyse, separately, how a ceiling-suspended lead screen absorbs the scattered radiation, a series of measurements was carried out during single CA/PCI procedures performed with and without the protection. The lead eyewear may reduce the doses to the eye closest to the x-ray tube by a factor between 1.1 and 3.4, depending on its model and the physician's position. The effectiveness of the eyewear may, however, vary-even for the same model and physician-almost twofold between different working periods. The ceiling-suspended shield decreases the doses in clinical practice by a factor of 2.3. The annual eye lens doses without the eyewear estimated from routine measurements are high above or close to the new eye lens dose limit established by the recent EU Basic Safety Standards, even though the ceiling-suspended shield was used. Therefore, to comply with the new dose limit that is set in the Directive, protection of the eyes of physicians with high workloads might require the use of both the eyewear and the ceiling-suspended shield. PMID- 27183001 TI - Predictors for Emergency Cesarean Delivery in Women with Placenta Previa. AB - Objective The objective of this study was to identify the predictors of emergency delivery in women with placenta previa. Methods This is a retrospective study of pregnancies complicated by placenta previa, scheduled for a cesarean delivery between 2001 and 2011. Using univariable and multivariable regression predictors for emergency delivery in these women were determined. Predictive performance was assessed using receiver operating characteristic analysis and calibration plot. Internal validation was performed by bootstrap analysis. Results Of 214 women with singleton pregnancies, 93 (43%) had an emergency cesarean delivery, and 43 (20%) were preterm. Independent predictors for emergency delivery were history of cesarean section (odds ratio [OR], 4.7; 95% confidence interval [CI], 1.2-12), antepartum bleeding with one (OR, 7.5; 95% CI, 2.5-23), two (OR, 14; 95% CI, 4.3 47), and three or more episodes (OR, 27; 95% CI, 8.3-90) as well as need for blood transfusion (OR, 6.4; 95% CI, 1.7-23). For emergency preterm delivery, covariates were comparable. The area under the curve was 0.832 on the original data and 0.821 on the bootstrap samples. Conclusion Predictors for emergency delivery in women with placenta previa can be used for individualized antenatal care concerning timing of delivery and corticosteroid cover. Potentially, careful selection in women with placenta previa can result in more conservative treatment in an outpatient setting and reduction of iatrogenic preterm delivery. PMID- 27183003 TI - Self-Assembled Dehydro[24]annulene Monolayers at the Liquid/Solid Interface: Toward On-Surface Synthesis of Tubular pi-Conjugated Nanowires. AB - We have studied the self-assembly behavior of dehydro[24]annulene (D24A) derivatives 1, 2a-2d, and 3a-3c at the liquid/solid interface using scanning tunneling microscopy (STM). Both the relative placement and the nature of the four D24A substituents strongly influence the self-assembly pattern. Overall, the eight D24A derivatives examined in this study display seven types of 2D packing patterns. The D24A derivatives 1, 2a, and 3a have either two or four stearate groups and adopt face-on configurations of their macrocyclic cores with respect to the highly oriented pyrolytic graphite (HOPG) surface. Their 2D packing pattern is determined by the interchain spacings and number of stearate substituents. The D24A derivatives 2b-2d and 3b-3c bear hydrogen-bonding carbamate groups to further strengthen intermolecular interactions. Face-on patterns were also observed for most of these compounds, while an unstable edge on self-assembly was observed in the case of 2b at room temperature. Stable edge on self-assemblies of D24A derivatives were sought for this work as an important stepping stone to achieving the on-surface topochemical polymerization of these carbon-rich macrocycles into tubular pi-conjugated nanowires. The overall factors determining the 2D packing patterns of D24As at the liquid/solid interface are discussed on the basis of theoretical simulations, providing useful guidelines for controlling the self-assembly pattern of future D24A macrocycles. PMID- 27183004 TI - Thermochemical Energy Storage through De/Hydrogenation of Organic Liquids: Reactions of Organic Liquids on Metal Hydrides. AB - A study of the reactions of liquid acetone and toluene on transition metal hydrides, which can be used in thermal energy or hydrogen storage applications, is presented. Hydrogen is confined in TiFe, Ti0.95Zr0.05Mn1.49V0.45Fe0.06 ("Hydralloy C5"), and V40Fe8Ti26Cr26 after contact with acetone. Toluene passivates V40Fe8Ti26Cr26 completely for hydrogen desorption while TiFe is only mildly deactivated and desorption is not blocked at all in the case of Hydralloy C5. LaNi5 is inert toward both organic liquids. Gas chromatography (GC) investigations reveal that CO, propane, and propene are formed during hydrogen desorption from V40Fe8Ti26Cr26 in liquid acetone, and methylcyclohexane is formed in the case of liquid toluene. These reactions do not occur if dehydrogenated samples are used, which indicates an enhanced surface reactivity during hydrogen desorption. Significant amounts of carbon-containing species are detected at the surface and subsurface of acetone- and toluene-treated V40Fe8Ti26Cr26 by X-ray photoelectron spectroscopy (XPS). The modification of the surface and subsurface chemistry and the resulting blocking of catalytic sites is believed to be responsible for the containment of hydrogen in the bulk. The surface passivation reactions occur only during hydrogen desorption of the samples. PMID- 27183005 TI - Unipolar distributions of junctional Myosin II identify cell stripe boundaries that drive cell intercalation throughout Drosophila axis extension. AB - Convergence and extension movements elongate tissues during development. Drosophila germ-band extension (GBE) is one example, which requires active cell rearrangements driven by Myosin II planar polarisation. Here, we develop novel computational methods to analyse the spatiotemporal dynamics of Myosin II during GBE, at the scale of the tissue. We show that initial Myosin II bipolar cell polarization gives way to unipolar enrichment at parasegmental boundaries and two further boundaries within each parasegment, concomitant with a doubling of cell number as the tissue elongates. These boundaries are the primary sites of cell intercalation, behaving as mechanical barriers and providing a mechanism for how cells remain ordered during GBE. Enrichment at parasegment boundaries during GBE is independent of Wingless signaling, suggesting pair-rule gene control. Our results are consistent with recent work showing that a combinatorial code of Toll like receptors downstream of pair-rule genes contributes to Myosin II polarization via local cell-cell interactions. We propose an updated cell-cell interaction model for Myosin II polarization that we tested in a vertex-based simulation. PMID- 27183008 TI - Is the patient able to watch TV or read the newspaper? A functional semi structured scale to observe Hemineglect symptoms in Activities of Daily Living (H ADL). AB - We developed a functional semi-structured scale to observe Hemineglect symptoms in Activities of Daily Living (H-ADL). The scale could assist clinicians in assessing rehabilitation priorities aimed at correcting any persisting errors or omissions. In addition, the scale could also be used by caregivers to observe patients' progress and improve their participation. Two groups of right brain damaged patients (25 with hemineglect; 27 without hemineglect) were tested twice: at admission and before discharge from hospital. A control group of healthy individuals matched to patients for age and education and patients' caregivers also participated. Two raters (A; B), experts in neuropsychology, observed patients and healthy individuals using the H-ADL. We found that the H-ADL final scores correlated with the standard hemineglect tests. The three groups differed in performance and differences also emerged between the first and the second assessment, suggesting an improvement due to the remission of hemineglect as a consequence of the treatment. Raters A and B did not differ in their observations, but there were some discrepancies with caregivers' observations. Therefore, although caregivers could help clinicians in detecting persistent hemineglect behaviour, the assessment should be performed by experts in neuropsychology. PMID- 27183009 TI - Fetal Tissue Procurement for Karyotype Analysis: Clinician or Pathologist - Which is Better? AB - Chromosomal abnormalities are detected in up to 13% of stillbirths and over 20% of those with developmental anomalies. These estimates may be low since up to 50% of samples fail to achieve a result due to microbial overgrowth or nonviability. Tissue for cytogenetics can be procured at bedside by the clinician or by the pathologist in the laboratory. With clinical collection, tissue is placed into culture media immediately, increasing chances of growth. However, collection competes for attention with other activities, which may result in microbial overgrowth or selection of maternal rather than fetal tissue. Laboratory procurement occurs in a controlled environment using sterile technique, but delay in collection may decrease viability. Our goal was to determine which collection method yields better results. METHODS: We reviewed cases from 2007-2013 that had two samples submitted for cytogenetics, one from the clinician and one from the pathologist. Specimen source, delivery, collection, and culture setup times, harvest date, cell growth, microbial overgrowth, maternal contamination and final result were obtained from medical records and cytogenetic culture sheets. FINDINGS: There was no difference in growth rate, maternal cell contamination, or reporting time between clinician- and pathologist-procured samples despite delay in collection time for laboratory samples. Clinical samples had more microbial overgrowth. Compared to samples collected at bedside, samples collected in the laboratory had a lower rate of microbial contamination with similar growth and maternal cell contamination rates, despite prolonged time to collection. Collecting samples both at bedside and in the laboratory is unnecessary. PMID- 27183006 TI - ERG signaling in prostate cancer is driven through PRMT5-dependent methylation of the Androgen Receptor. AB - The TMPRSS2:ERG gene fusion is common in androgen receptor (AR) positive prostate cancers, yet its function remains poorly understood. From a screen for functionally relevant ERG interactors, we identify the arginine methyltransferase PRMT5. ERG recruits PRMT5 to AR-target genes, where PRMT5 methylates AR on arginine 761. This attenuates AR recruitment and transcription of genes expressed in differentiated prostate epithelium. The AR-inhibitory function of PRMT5 is restricted to TMPRSS2:ERG-positive prostate cancer cells. Mutation of this methylation site on AR results in a transcriptionally hyperactive AR, suggesting that the proliferative effects of ERG and PRMT5 are mediated through attenuating AR's ability to induce genes normally involved in lineage differentiation. This provides a rationale for targeting PRMT5 in TMPRSS2:ERG positive prostate cancers. Moreover, methylation of AR at arginine 761 highlights a mechanism for how the ERG oncogene may coax AR towards inducing proliferation versus differentiation. PMID- 27183007 TI - 5-hydroxymethylcytosine marks regions with reduced mutation frequency in human DNA. AB - CpG dinucleotides are the main mutational hot-spot in most cancers. The characteristic elevated C>T mutation rate in CpG sites has been related to 5 methylcytosine (5mC), an epigenetically modified base which resides in CpGs and plays a role in transcription silencing. In brain nearly a third of 5mCs have recently been found to exist in the form of 5-hydroxymethylcytosine (5hmC), yet the effect of 5hmC on mutational processes is still poorly understood. Here we show that 5hmC is associated with an up to 53% decrease in the frequency of C>T mutations in a CpG context compared to 5mC. Tissue specific 5hmC patterns in brain, kidney and blood correlate with lower regional CpG>T mutation frequency in cancers originating in the respective tissues. Together our data reveal global and opposing effects of the two most common cytosine modifications on the frequency of cancer causing somatic mutations in different cell types. PMID- 27183010 TI - Discriminating Intercalative Effects of Threading Intercalator Nogalamycin, from Classical Intercalator Daunomycin, Using Single Molecule Atomic Force Spectroscopy. AB - DNA threading intercalators are a unique class of intercalating agents, albeit little biophysical information is available on their intercalative actions. Herein, the intercalative effects of nogalamycin, which is a naturally-occurring DNA threading intercalator, have been investigated by high-resolution atomic force microscopy (AFM) and spectroscopy (AFS). The results have been compared with those of the well-known chemotherapeutic drug daunomycin, which is a non threading classical intercalator bearing structural similarity to nogalamycin. A comparative AFM assessment revealed a greater increase in DNA contour length over the entire incubation period of 48 h for nogalamycin treatment, whereas the contour length increase manifested faster in case of daunomycin. The elastic response of single DNA molecules to an externally applied force was investigated by the single molecule AFS approach. Characteristic mechanical fingerprints in the overstretching behaviour clearly distinguished the nogalamycin/daunomycin treated dsDNA from untreated dsDNA-the former appearing less elastic than the latter, and the nogalamycin-treated DNA distinguished from the daunomycin-treated DNA-the classically intercalated dsDNA appearing the least elastic. A single molecule AFS-based discrimination of threading intercalation from the classical type is being reported for the first time. PMID- 27183011 TI - Enhanced cell-surface display and secretory production of cellulolytic enzymes with Saccharomyces cerevisiae Sed1 signal peptide. AB - Recombinant yeast strains displaying aheterologous cellulolytic enzymes on their cell surfaces using a glycosylphosphatidylinositol (GPI) anchoring system are a promising strategy for bioethanol production from lignocellulosic materials. A crucial step for cell wall localization of the enzymes is the intracellular transport of proteins in yeast cells. Therefore, the addition of a highly efficient secretion signal sequence is important to increase the amount of the enzymes on the yeast cell surface. In this study, we demonstrated the effectiveness of a novel signal peptide (SP) sequence derived from the Saccharomyces cerevisiae SED1 gene for cell-surface display and secretory production of cellulolytic enzymes. Gene cassettes with SP sequences derived from S. cerevisiae SED1 (SED1SP), Rhizopus oryzae glucoamylase (GLUASP), and S. cerevisiae alpha-mating pheromone (MFalpha1SP) were constructed for cell-surface display of Aspergillus aculeatus beta-glucosidase (BGL1) and Trichoderma reesei endoglucanase II (EGII). These gene cassettes were integrated into the S. cerevisiae genome. The recombinant strains with the SED1SP showed higher cell surface BGL and EG activities than those with the conventional SP sequences (GLUASP and MFalpha1SP). The novel SP sequence also improved the secretory production of BGL and EG in S. cerevisiae. The extracellular BGL activity of the recombinant strains with the SED1SP was 1.3- and 1.9-fold higher than the GLUASP and MFalpha1SP strains, respectively. Moreover, the utilization of SED1SP successfully enhanced the secretory production of BGL in Pichia pastoris. The utilization of the novel SP sequence is a promising option for highly efficient cell-surface display and secretory production of heterologous proteins in various yeast species. Biotechnol. Bioeng. 2016;113: 2358-2366. (c) 2016 Wiley Periodicals, Inc. PMID- 27183025 TI - Determinants of Urinary Output Response to IV Furosemide in Acute Kidney Injury: A Pharmacokinetic/Pharmacodynamic Study. AB - OBJECTIVES: This study assessed the determinants of urinary output response to furosemide in acute kidney injury; specifically, whether the response is related to altered pharmacokinetics or pharmacodynamics. DESIGN: Prospective cohort. SETTING: Tertiary ICU. PATIENTS: Thirty critically ill patients with acute kidney injury without preexisting renal impairment or recent diuretic exposure. INTERVENTION: A single dose of IV furosemide. MEASUREMENTS AND MAIN RESULTS: Baseline markers of intravascular volume status were obtained prior to administering furosemide. Six-hour creatinine clearance, hourly plasma/urinary furosemide concentrations, and hourly urinary output were used to assess furosemide pharmacokinetics/pharmacodynamics parameters. Of 30 patients enrolled, 11 had stage-1 (37%), nine had stage-2 (30%), and 10 had stage-3 (33%) Acute Kidney Injury Network acute kidney injury. Seventy-three percent were septic, 47% required norepinephrine, and 53% were mechanically ventilated. Urinary output doubled in 20 patients (67%) following IV furosemide. Measured creatinine clearance was strongly associated with the amount of urinary furosemide excreted and was the only reliable predictor of the urinary output after furosemide (area under the receiver-operating-characteristic curve, 0.75; 95% CI, 0.57-0.93). In addition to an altered pharmacokinetics (p < 0.01), a reduced pharmacodynamics response to furosemide also became important when creatinine clearance was reduced to less than 40 mL/min/1.73 m (p = 0.01). Acute kidney injury staging and markers of intravascular volume, including central venous pressure, brain natriuretic-peptide concentration, and fractional urinary sodium excretion were not predictive of urinary output response to furosemide. CONCLUSIONS: The severity of acute kidney injury, as reflected by the measured creatinine clearance, alters both pharmacokinetics and pharmacodynamics of furosemide in acute kidney injury, and was the only reliable predictor of the urinary output response to furosemide in acute kidney injury. PMID- 27183026 TI - Split-face comparison between single-band and dual-band pulsed light technology for treatment of photodamage. AB - BACKGROUND: Intense pulsed light (IPL) has a well-recognized role in the treatment of photodamaged skin. OBJECTIVE: To assess the safety and efficacy of a novel single-band IPL handpiece versus dual-band IPL handpiece in the treatment of photodamage. STUDY DESIGN/MATERIALS AND METHODS: This was a prospective, single-center split-face study with 20 enrolled participants. Three treatments, 21 days apart, were administered to the subjects and follow-up was performed for 20 weeks. The left side of the face was treated with the single-band handpiece. The right side of the face was treated with the dual-band handpiece. Blinded investigators assessed the subjects' skin texture, pigmented components of photodamage, and presence of telangiectasia both before and after treatment, utilizing a five-point scale. RESULTS: Pigmented components of photodamage, skin texture, and presence of telangiectasias on the left and right side of the face were improved at the end of treatment. At 20-week follow-up, the side treated with single-band handpiece showed improvement in telangiectasia and pigmentation that was statistically superior to the contralateral side treated with the dual band handpiece. Both devices equally improved textural changes. No adverse effects were noted with either device. CONCLUSION: Both single-band and dual-band IPL technology are safe and effective in the treatment of photodamaged facial skin. IPL treatment with a single-band handpiece yielded results comparable or superior to dual-band technology. PMID- 27183027 TI - Immunotherapy for genitourinary cancer: state of the art and new perspectives. AB - In the last few years, cancer immunotherapy has changed the natural history and treatment strategies of a number of solid tumors, including melanoma and lung cancer. The anti-PD-1 nivolumab showed a survival benefit compared with everolimus in the second-line treatment of renal cell carcinoma, resulting in a radical shift in perspective in the treatment of this neoplasia and suggesting a new scenario beyond tyrosine kinase inhibitors. Checkpoint inhibitors might also improve the treatment of urothelial cancer, considering the promising results achieved so far and the relatively low efficacy of currently available treatments. Sipuleucel-T was the first approved immunotherapy for prostate cancer, showing a clear benefit in overall survival, and paved the way for the clinical testing of other novel cancer vaccines. This review provides a comprehensive overview of the current knowledge and new perspectives of immunotherapy in the treatment of urogenital malignancies. PMID- 27183029 TI - Ultrathin Films of VO2 on r-Cut Sapphire Achieved by Postdeposition Etching. AB - The metal-insulator transition (MIT) properties of correlated oxides thin films, such as VO2, are dramatically affected by strain induced at the interface with the substrate, which usually changes with deposition thickness. For VO2 grown on r-cut sapphire, there is a minimum deposition thickness required for a significant MIT to appear, around 60 nm. We show that in these thicker films an interface layer develops, which accompanies the relaxation of film strain and enhanced electronic transition. If these interface dislocations are stable at room temperature, we conjectured, a new route opens to control thickness of VO2 films by postdeposition thinning of relaxed films, overcoming the need for thickness-dependent strain-engineered substrates. This is possible only if thinning does not alter the films' electronic properties. We find that wet etching in a dilute NaOH solution can effectively thin the VO2 films, which continue to show a significant MIT, even when etched to 10 nm, for which directly deposited films show nearly no transition. The structural and chemical composition were not modified by the etching, but the grain size and film roughness were, which modified the hysteresis width and magnitude of the MIT resistance change. PMID- 27183028 TI - Human Collagen Prolyl 4-Hydroxylase Is Activated by Ligands for Its Iron Center. AB - Collagen is the most abundant protein in animals. The posttranslational hydroxylation of proline residues in collagen contributes greatly to its conformational stability. Deficient hydroxylation is associated with a variety of disease states, including scurvy. The hydroxylation of proline residues in collagen is catalyzed by an Fe(II)- and alpha-ketoglutarate-dependent dioxygenase, collagen prolyl 4-hydroxylase (CP4H). CP4H has long been known to suffer oxidative inactivation during catalysis, and the cofactor ascorbate (vitamin C) is required to reactivate the enzyme by reducing its iron center from Fe(III) to Fe(II). Herein, we report on the discovery of the first synthetic activators of CP4H. Specifically, we find that 2,2'-bipyridine-4-carboxylate and 2,2'-bipyridine-5-carboxylate serve as ligands for the iron center in human CP4H that enhance the rate of ascorbate-dependent reactivation. This new mode of CP4H activation is available to other biheteroaryl compounds but does not necessarily extend to other prolyl 4-hydroxylases. As collagen is weakened in many indications, analogous activators of CP4H could have therapeutic benefits. PMID- 27183030 TI - Well-Defined Nanostructured, Single-Crystalline TiO2 Electron Transport Layer for Efficient Planar Perovskite Solar Cells. AB - An electron transporting layer (ETL) plays an important role in extracting electrons from a perovskite layer and blocking recombination between electrons in the fluorine-doped tin oxide (FTO) and holes in the perovskite layers, especially in planar perovskite solar cells. Dense TiO2 ETLs prepared by a solution processed spin-coating method (S-TiO2) are mainly used in devices due to their ease of fabrication. Herein, we found that fatal morphological defects at the S TiO2 interface due to a rough FTO surface, including an irregular film thickness, discontinuous areas, and poor physical contact between the S-TiO2 and the FTO layers, were inevitable and lowered the charge transport properties through the planar perovskite solar cells. The effects of the morphological defects were mitigated in this work using a TiO2 ETL produced from sputtering and anodization. This method produced a well-defined nanostructured TiO2 ETL with an excellent transmittance, single-crystalline properties, a uniform film thickness, a large effective area, and defect-free physical contact with a rough substrate that provided outstanding electron extraction and hole blocking in a planar perovskite solar cell. In planar perovskite devices, anodized TiO2 ETL (A-TiO2) increased the power conversion efficiency by 22% (from 12.5 to 15.2%), and the stabilized maximum power output efficiency increased by 44% (from 8.9 to 12.8%) compared with S-TiO2. This work highlights the importance of the ETL geometry for maximizing device performance and provides insights into achieving ideal ETL morphologies that remedy the drawbacks observed in conventional spin-coated ETLs. PMID- 27183031 TI - SAFETY AND EFFICACY OF INTRAVITREAL DEXAMETHASONE IMPLANTS IN THE MANAGEMENT OF MACULAR EDEMA SECONDARY TO INFECTIOUS UVEITIS. AB - PURPOSE: To assess the safety and efficacy of intravitreal dexamethasone implants in the treatment of macular edema secondary to infectious uveitis. METHODS: We retrospectively reviewed clinical records from three uveitis referral units in Spain. The main outcome measures were rate of reactivation of infection, improvements in visual acuity and resolution of macular edema, as measured by optical coherence tomography. RESULTS: We included eight eyes from seven patients with a median age of 64 years (30-75). Etiologies of the infections were Herpes simplex virus-type 1, Varicela-Zoster virus, Treponema pallidum, Brucella mellitensis, Borrelia burgdorferi, Toxoplasma gondii, and cytomegalovirus. Median visual acuity was 20/160 (20/30-20/400) at baseline and 20/70 (20/25-20/200) at the last follow-up visit. Mean macular thickness was 516 MUm (115) at baseline and 266.3 MUm (40) at the last follow-up visit. Visual acuity improved in 100% of the eyes and none of the eyes showed macular edema at the last follow-up visit. Five patients required reinjections of the implant. Only one patient required antiglaucoma drops for a temporary increase in ocular pressure. There were no cases of reactivation of the infectious ocular disease. Median follow-up time was 18 months. CONCLUSION: In this small case series of eyes with macular edema secondary to infectious uveitis, treatment with dexamethasone intravitreal implants was not associated with reactivation of the infectious ocular disease. Furthermore, significant improvements in visual acuity and macular thickness were observed in our patients. PMID- 27183034 TI - Polymorphic Lanthanide Phosphonates Showing Distinct Magnetic Behavior. AB - A series of layered lanthanide phosphonates alpha-Ln(2-qpH)(SO4)(H2O)2 (alpha-Ln; Ln = Gd, Tb, Ho, Er) and beta-Ln(2-qpH)(SO4)(H2O)2 (beta-Ln; Ln = Gd, Tb, Ho, Er, Yb) (2-qpH2 = 2-quinolinephosphonic acid) have been synthesized and characterized. Compounds alpha-Ln crystallize in monoclinic space group P21/c, while compounds beta-Ln crystallize in triclinic space group P1. Magnetic studies reveal that dominant ferromagnetic interactions are propagated between the magnetic centers in all cases. Field-induced magnetic relaxation is observed in compounds beta-Er and beta-Yb. PMID- 27183033 TI - Silver-Ion Solid Phase Extraction Separation of Classical, Aromatic, Oxidized, and Heteroatomic Naphthenic Acids from Oil Sands Process-Affected Water. AB - The separation of classical, aromatic, oxidized, and heteroatomic (sulfur containing) naphthenic acid (NA) species from unprocessed and ozone-treated oil sands process-affected water (OSPW) was performed using silver-ion (Ag-ion) solid phase extraction (SPE) without the requirement of pre-methylation for NAs. OSPW samples before SPE and SPE fractions were characterized using ultra performance liquid chromatography ion mobility time-of-flight mass spectrometry (UPLC-IM TOFMS) to corroborate the separation of distinct NA species. The mass spectrum identification applied a mass tolerance of +/-1.5 mDa due to the mass errors of NAs were measured within this range, allowing the identification of O2S-NAs from O2-NAs. Moreover, separated NA species facilitated the tandem mass spectrometry (MS/MS) characterization of NA compounds due to the removal of matrix and a simplified composition. MS/MS results showed that classical, aromatic, oxidized, and sulfur-containing NA compounds were eluted into individual SPE fractions. Overall results indicated that the separation of NA species using Ag-ion SPE is a valuable method for extracting individual NA species that are of great interest for environmental toxicology and wastewater treatment research, to conduct species-specific studies. Furthermore, the separated NA species on the milligram level could be widely used as the standard materials for environmental monitoring of NAs from various contamination sites. PMID- 27183032 TI - Association of Leisure-Time Physical Activity With Risk of 26 Types of Cancer in 1.44 Million Adults. AB - IMPORTANCE: Leisure-time physical activity has been associated with lower risk of heart-disease and all-cause mortality, but its association with risk of cancer is not well understood. OBJECTIVE: To determine the association of leisure-time physical activity with incidence of common types of cancer and whether associations vary by body size and/or smoking. DESIGN, SETTING, AND PARTICIPANTS: We pooled data from 12 prospective US and European cohorts with self-reported physical activity (baseline, 1987-2004). We used multivariable Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals for associations of leisure-time physical activity with incidence of 26 types of cancer. Leisure-time physical activity levels were modeled as cohort-specific percentiles on a continuous basis and cohort-specific results were synthesized by random-effects meta-analysis. Hazard ratios for high vs low levels of activity are based on a comparison of risk at the 90th vs 10th percentiles of activity. The data analysis was performed from January 1, 2014, to June 1, 2015. EXPOSURES: Leisure-time physical activity of a moderate to vigorous intensity. MAIN OUTCOMES AND MEASURES: Incident cancer during follow-up. RESULTS: A total of 1.44 million participants (median [range] age, 59 [19-98] years; 57% female) and 186 932 cancers were included. High vs low levels of leisure-time physical activity were associated with lower risks of 13 cancers: esophageal adenocarcinoma (HR, 0.58; 95% CI, 0.37-0.89), liver (HR, 0.73; 95% CI, 0.55-0.98), lung (HR, 0.74; 95% CI, 0.71-0.77), kidney (HR, 0.77; 95% CI, 0.70-0.85), gastric cardia (HR, 0.78; 95% CI, 0.64-0.95), endometrial (HR, 0.79; 95% CI, 0.68-0.92), myeloid leukemia (HR, 0.80; 95% CI, 0.70-0.92), myeloma (HR, 0.83; 95% CI, 0.72-0.95), colon (HR, 0.84; 95% CI, 0.77-0.91), head and neck (HR, 0.85; 95% CI, 0.78-0.93), rectal (HR, 0.87; 95% CI, 0.80-0.95), bladder (HR, 0.87; 95% CI, 0.82-0.92), and breast (HR, 0.90; 95% CI, 0.87-0.93). Body mass index adjustment modestly attenuated associations for several cancers, but 10 of 13 inverse associations remained statistically significant after this adjustment. Leisure-time physical activity was associated with higher risks of malignant melanoma (HR, 1.27; 95% CI, 1.16 1.40) and prostate cancer (HR, 1.05; 95% CI, 1.03-1.08). Associations were generally similar between overweight/obese and normal-weight individuals. Smoking status modified the association for lung cancer but not other smoking-related cancers. CONCLUSIONS AND RELEVANCE: Leisure-time physical activity was associated with lower risks of many cancer types. Health care professionals counseling inactive adults should emphasize that most of these associations were evident regardless of body size or smoking history, supporting broad generalizability of findings. PMID- 27183036 TI - Role of Local Response in Ion Solvation: Born Theory and Beyond. AB - The nature of ion solvation has drawn the interest of scientists for over a century, yet a thorough theoretical understanding is still lacking. In this work, we focus on the microscopic origins underlying ionic charge asymmetric and nonlinear response contributions to ion solvation free energies. We first derive an exact expression for the charging component of the ionic free energy, the free energy change when the Coulomb interactions between a fixed ion and the solvent are gradually "turned on". We then introduce the concept of a Gaussian test charge distribution, a generalization of the classical electrostatic point test charge that can be used to probe dielectric response in atomically detailed models. This enables the study of a thermodynamic cycle that isolates a linear and charge-symmetric contribution to the free energy that is well-described by Born-model-like dielectric continuum theories. We give a simple physical derivation of the classic Born model that locally relates the induced charge density in a linear dielectric model to the applied ionic charge distribution. The nonlinear response and charge asymmetric contributions to the ion solvation free energy are then examined in the remaining steps of the cycle and compared to classic thermodynamic cycles for this process using computer simulations. The insights provided by this work will aid the development of quantitative theories for the solvation of charged solutes. PMID- 27183035 TI - Comparative Effectiveness of Tai Chi Versus Physical Therapy for Knee Osteoarthritis: A Randomized Trial. AB - BACKGROUND: Few remedies effectively treat long-term pain and disability from knee osteoarthritis. Studies suggest that Tai Chi alleviates symptoms, but no trials have directly compared Tai Chi with standard therapies for osteoarthritis. OBJECTIVE: To compare Tai Chi with standard physical therapy for patients with knee osteoarthritis. DESIGN: Randomized, 52-week, single-blind comparative effectiveness trial. (ClinicalTrials.gov: NCT01258985). SETTING: An urban tertiary care academic hospital. PATIENTS: 204 participants with symptomatic knee osteoarthritis (mean age, 60 years; 70% women; 53% white). INTERVENTION: Tai Chi (2 times per week for 12 weeks) or standard physical therapy (2 times per week for 6 weeks, followed by 6 weeks of monitored home exercise). MEASUREMENTS: The primary outcome was Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score at 12 weeks. Secondary outcomes included physical function, depression, medication use, and quality of life. RESULTS: At 12 weeks, the WOMAC score was substantially reduced in both groups (Tai Chi, 167 points [95% CI, 145 to 190 points]; physical therapy, 143 points [CI, 119 to 167 points]). The between-group difference was not significant (24 points [CI, -10 to 58 points]). Both groups also showed similar clinically significant improvement in most secondary outcomes, and the benefits were maintained up to 52 weeks. Of note, the Tai Chi group had significantly greater improvements in depression and the physical component of quality of life. The benefit of Tai Chi was consistent across instructors. No serious adverse events occurred. LIMITATION: Patients were aware of their treatment group assignment, and the generalizability of the findings to other settings remains undetermined. CONCLUSION: Tai Chi produced beneficial effects similar to those of a standard course of physical therapy in the treatment of knee osteoarthritis. PRIMARY FUNDING SOURCE: National Center for Complementary and Integrative Health of the National Institutes of Health. PMID- 27183037 TI - Influence of density and environmental factors on decomposition kinetics of amorphous polylactide - Reactive molecular dynamics studies. AB - In this work, we investigate the influence of the surrounding environment and the initial density on the decomposition kinetics of polylactide (PLA). The decomposition of the amorphous PLA was investigated by means of reactive molecular dynamics simulations. A computational model simulates the decomposition of PLA polymer inside the bulk, due to the assumed lack of removal of reaction products from the polymer matrix. We tracked the temperature dependency of the water and carbon monoxide production to extract the activation energy of thermal decomposition of PLA. We found that an increased density results in decreased activation energy of decomposition by about 50%. Moreover, initiation of decomposition of the amorphous PLA is followed by a rapid decline in activation energy caused by reaction products which accelerates the hydrolysis of esters. The addition of water molecules decreases initial energy of activation as well as accelerates the decomposition process. Additionally, we have investigated the dependency of density on external loading. Comparison of pressures needed to obtain assumed densities shows that this relationship is bilinear and the slope changes around a density equal to 1.3g/cm(3). The conducted analyses provide an insight into the thermal decomposition process of the amorphous phase of PLA, which is particularly susceptible to decomposition in amorphous and semi crystalline PLA polymers. PMID- 27183038 TI - Sequencing of the Litchi Downy Blight Pathogen Reveals It Is a Phytophthora Species With Downy Mildew-Like Characteristics. AB - On the basis of its downy mildew-like morphology, the litchi downy blight pathogen was previously named Peronophythora litchii. Recently, however, it was proposed to transfer this pathogen to Phytophthora clade 4. To better characterize this unusual oomycete species and important fruit pathogen, we obtained the genome sequence of Phytophthora litchii and compared it to those from other oomycete species. P. litchii has a small genome with tightly spaced genes. On the basis of a multilocus phylogenetic analysis, the placement of P. litchii in the genus Phytophthora is strongly supported. Effector proteins predicted included 245 RxLR, 30 necrosis-and-ethylene-inducing protein-like, and 14 crinkler proteins. The typical motifs, phylogenies, and activities of these effectors were typical for a Phytophthora species. However, like the genome features of the analyzed downy mildews, P. litchii exhibited a streamlined genome with a relatively small number of genes in both core and species-specific protein families. The low GC content and slight codon preferences of P. litchii sequences were similar to those of the analyzed downy mildews and a subset of Phytophthora species. Taken together, these observations suggest that P. litchii is a Phytophthora pathogen that is in the process of acquiring downy mildew-like genomic and morphological features. Thus P. litchii may provide a novel model for investigating morphological development and genomic adaptation in oomycete pathogens. PMID- 27183040 TI - Exciton Correlations in Intramolecular Singlet Fission. AB - We have synthesized a series of asymmetric pentacene-tetracene heterodimers with a variable-length conjugated bridge that undergo fast and efficient intramolecular singlet fission (iSF). These compounds have distinct singlet and triplet energies, which allow us to study the spatial dynamics of excitons during the iSF process, including the significant role of exciton correlations in promoting triplet pair generation and recombination. We demonstrate that the primary photoexcitations in conjugated dimers are delocalized singlets that enable fast and efficient iSF. However, in these asymmetric dimers, the singlet becomes more localized on the lower energy unit as the length of the bridge is increased, slowing down iSF relative to analogous symmetric dimers. We resolve the recombination kinetics of the inequivalent triplets produced via iSF, and find that they primarily decay via concerted processes. By identifying different decay channels, including delayed fluorescence via triplet-triplet annihilation, we can separate transient species corresponding to both correlated triplet pairs and uncorrelated triplets. Recombination of the triplet pair proceeds rapidly despite our experimental and theoretical demonstration that individual triplets are highly localized and unable to be transported across the conjugated linker. In this class of compounds, the rate of formation and yield of uncorrelated triplets increases with bridge length. Overall, these constrained, asymmetric systems provide a unique platform to isolate and study transient species essential for singlet fission, which are otherwise difficult to observe in symmetric dimers or condensed phases. PMID- 27183039 TI - A Dicarboxylate Transporter, LjALMT4, Mainly Expressed in Nodules of Lotus japonicus. AB - Legume plants can establish symbiosis with soil bacteria called rhizobia to obtain nitrogen as a nutrient directly from atmospheric N2 via symbiotic nitrogen fixation. Legumes and rhizobia form nodules, symbiotic organs in which fixed nitrogen and photosynthetic products are exchanged between rhizobia and plant cells. The photosynthetic products supplied to rhizobia are thought to be dicarboxylates but little is known about the movement of dicarboxylates in the nodules. In terms of dicarboxylate transporters, an aluminum-activated malate transporter (ALMT) family is a strong candidate responsible for the membrane transport of carboxylates in nodules. Among the seven ALMT genes in the Lotus japonicus genome, only one, LjALMT4, shows a high expression in the nodules. LjALMT4 showed transport activity in a Xenopus oocyte system, with LjALMT4 mediating the efflux of dicarboxylates including malate, succinate, and fumarate, but not tricarboxylates such as citrate. LjALMT4 also mediated the influx of several inorganic anions. Organ-specific gene expression analysis showed LjALMT4 mRNA mainly in the parenchyma cells of nodule vascular bundles. These results suggest that LjALMT4 may not be involved in the direct supply of dicarboxylates to rhizobia in infected cells but is responsible for supplying malate as well as several anions necessary for symbiotic nitrogen fixation, via nodule vasculatures. PMID- 27183041 TI - Evolving Government Policy on Opioid Availability and Use Is a Double-edged Sword. PMID- 27183042 TI - Factors Associated with Breastfeeding Initiation and Exclusive Breastfeeding Rates in Turkish Adolescent Mothers. AB - OBJECTIVE: This study aimed to determine the early initiation time of breastfeeding and exclusive breastfeeding (EBF) rates during the first 6 months and the main factors affecting EBF practice in Turkish adolescent mothers. STUDY DESIGN AND METHODS: A cross-sectional study was conducted with 200 adolescent mothers who were raising 6 to 24 month-old children. A face-to-face interview was conducted for sociodemographic characteristics, obstetric history, information about the baby, information about breastfeeding, and the factors affecting breastfeeding. We detected breastfeeding prevalence as well as its initiation time and duration. RESULTS: The mean age of the patients was 17.9 +/- 1.15 years. The percentage of patients who started breastfeeding within 1 hour was 45.5%. Approximately, 74% of the adolescent mothers provided breastfeeding before any type of formula as the baby's first food. Women who initiated breastfeeding earlier had planned pregnancies, educated for breastfeeding, delivered vaginally, and had boy infants. The mothers who started breastfeeding earlier fed their babies significantly more frequently at night, had longer EBF times, and had longer total breastfeeding times than the mothers who started breastfeeding later than 2 hours. Planned pregnancy, vaginal delivery, and having a boy infant were significantly associated with early breastfeeding. Age, planned pregnancy, postpartum education, frequent breastfeeding at night, and formula initiation time were predictors of EBF. CONCLUSIONS: Adolescent pregnants may start breastfeeding earlier when had planned pregnancy, educated and encouraged for breastfeeding from the family and medical staff. Therefore, strategies should be formed to improve breastfeeding programs. PMID- 27183043 TI - Low reliability of sighted-normed verbal assessment scores when administered to children with visual impairments. AB - The most common and advocated assessment approach when a child cannot access visual materials is to use the verbal subscales of a test the psychologist already has and is familiar with. However, previous research indicates that children with visual impairments experience atypical verbal development. This raises the question of whether verbal subscale scores retain their reliability and interpretation validity when given to children with visual impairments. To answer this question, we administered a vocabulary subscale from a common intelligence test along with several nonverbal subscales to 15 early-blind adolescents (onset of <=2 years). Reliability of only the vocabulary test scores was insufficient for high-stakes testing. This finding points to the broader issue of difficulties in assessing populations of exceptional children who experience atypical development trajectories, possibly making their assessment with common tests inappropriate. (PsycINFO Database Record PMID- 27183044 TI - The influence of different criteria for establishing optimal cutoff scores on performance of two self-report measures for warzone PTSD. AB - Posttraumatic stress disorder (PTSD) has been regarded as a signature injury of war and elevated to one of the major behavioral health problems faced by military service members and veterans deployed to warzones. In PTSD diagnosis, self-report measures have often been used with a cutoff score to identify those with an elevated likelihood of having PTSD prior to conducting a second-tier diagnostic interview. With an attempt to guide the selection of cutoffs in self-report PTSD measures for various purposes, this study examined how five common criteria for establishing an optimal cutoff influenced the performance of self-report measures for warzone PTSD in relation to the Clinician Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) and whether the influence differed for the PTSD Checklist for DSM-5 and the Mississippi Scale for Combat-Related PTSD. Using a probability sample of Vietnam theater veterans in the National Vietnam Veterans Longitudinal Study, results showed that in both self-report measures, the Youden Index criterion yielded the optimal cutoff that led to better test performance. (PsycINFO Database Record PMID- 27183045 TI - Validation of the Dyadic Coping Inventory with Chinese couples: Factorial structure, measurement invariance, and construct validity. AB - The Dyadic Coping Inventory (DCI, Bodenmann, 2008) assesses how couples support each other when facing individual (e.g., workload) and common (e.g., parenting) stressors. Specifically, the DCI measures partners' perceptions of their own (Self) and their partners' behaviors (Partner) when facing individual stressors, and partners' common coping behaviors when facing common stressors (Common). To date, the DCI has been validated in 6 different languages from individualistic Western cultures; however, because culture can affect interpersonal interactions, it is unknown whether the DCI is a reliable measure of coping behaviors for couples living in collectivistic Eastern cultures. Based on data from 474 Chinese couples (N = 948 individuals), the current study examined the Chinese version of the DCI's factorial structure, measurement invariance (MI), and construct validity of test scores. Using 3 cultural groups (China, Switzerland, and the United States [U.S.]), confirmatory factor analysis revealed a 5-factor structure regarding Self and Partner and a 2-factor structure regarding Common dyadic coping (DC). Results from analyses of MI indicated that the DCI subscales met the criteria for configural, metric, and full/partial scalar invariance across cultures (Chinese-Swiss and Chinese-U.S.) and genders (Chinese men and women). Results further revealed good construct validity of the DCI test scores. In all, the Chinese version of the DCI can be used for measuring Chinese couples' coping behaviors, and is available for cross-cultural studies examining DC behaviors between Western and Eastern cultures. (PsycINFO Database Record PMID- 27183046 TI - The comparative capacity of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) and MMPI-2 Restructured Form (MMPI-2-RF) validity scales to detect suspected malingering in a disability claimant sample. AB - The current study expands on past research examining the comparative capacity of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2; Butcher et al., 2001) and MMPI-2 Restructured Form (MMPI-2-RF; Ben-Porath & Tellegen, 2008/2011) overreporting validity scales to detect suspected malingering, as assessed by the Miller Forensic Assessment of Symptoms Test (M-FAST; Miller, 2001), in a sample of public insurance disability claimants (N = 742) who were considered to have potential incentives to malinger. Results provide support for the capacity of both the MMPI-2 and the MMPI-2-RF overreporting validity scales to predict suspected malingering of psychopathology. The MMPI-2-RF overreporting validity scales proved to be modestly better predictors of suspected psychopathology malingering-compared with the MMPI-2 overreporting scales-in dimensional predictive models and categorical classification accuracy analyses. (PsycINFO Database Record PMID- 27183048 TI - Do donor oocyte cycles comply with ASRM/SART embryo transfer guidelines? An analysis of 13,393 donor cycles from the SART registry. AB - OBJECTIVE: To analyze donor oocyte cycles in the Society for Assisted Reproductive Technology (SART) registry to determine: 1) how many cycles complied with the 2009 American Society for Reproductive Medicine/SART embryo transfer guidelines; and 2) cycle outcomes according to the number of embryos transferred. For donor oocyte IVF with donor age <35 years, the consideration of single-embryo transfer was strongly recommended. DESIGN: Retrospective cohort study of United States national registry information. SETTING: Not applicable. PATIENT(S): A total of 13,393 donor-recipient cycles from 2011 to 2012. INTERVENTION(S): Embryos transferred in donor IVF cycles. MAIN OUTCOME MEASURE(S): Percentage of compliant cycles, multiple pregnancy rate. RESULT(S): There were 3,157 donor cleavage-stage transfers and 10,236 donor blastocyst transfers. In the cleavage stage cycles, 88% met compliance criteria. The multiple pregnancy rate (MPR) was significantly higher in the noncompliant cycles. In a subanalysis of compliant cleavage-stage cycles, 91% transferred two embryos and only 9% single embryos. In those patients transferring two embryos, the MPR was significantly higher (33% vs. 1%). In blastocyst transfers, only 28% of the cycles met compliance criteria. The MPR was significantly higher in the noncompliant blastocyst cohort at 53% (compared with 2% in compliant cycles). CONCLUSION(S): The majority of donor cleavage-stage transfers are compliant with current guidelines, but the transfer of two embryos results in a significantly higher MPR compared with single-embryo transfer. The majority of donor blastocyst cycles are noncompliant, which appears to be driving an unacceptably high MPR in these cycles. PMID- 27183047 TI - Association of bilateral oophorectomy with cognitive function in healthy, postmenopausal women. AB - OBJECTIVE: To investigate the association between bilateral oophorectomy and cognitive performance in healthy, older women. DESIGN: Retrospective analysis of clinical trial data. SETTING: Academic research institution. PATIENT(S): Healthy postmenopausal women without signs or symptoms of cardiovascular disease or diabetes (n = 926). INTERVENTION(S): Randomized interventions (not the focus of this analysis) in analyzed trials included B-vitamins, soy isoflavones, oral estradiol, and matching placebos. MAIN OUTCOME MEASURE(S): Measures in five cognitive domains (executive functions, semantic memory, logical memory, visual memory, and verbal learning) and global cognitive function. RESULT(S): Using data from three clinical trials conducted under uniform conditions, bilateral oophorectomy and its timing were analyzed cross-sectionally and longitudinally in relation to cognitive function in linear regression models. Covariates included age, education, race/ethnicity, body mass index, trial, and randomized treatment (in longitudinal models). Duration of menopausal hormone use was considered as a possible mediator and effect modifier. Median age of oophorectomy was 45 years. When evaluating baseline cognition, we found that surgical menopause after 45 years of age was associated with lower performance in verbal learning compared with natural menopause. Evaluating the change in cognition over approximately 2.7 years, surgical menopause was associated with performance declines in visual memory for those who had an oophorectomy after 45 years of age and in semantic memory for those who had oophorectomy before 45 years of age compared with natural menopause. Oophorectomy after natural menopause was not associated with cognitive performance. Adjustment for duration of hormone use did not alter these associations. CONCLUSION(S): Cognitive associations with ovarian removal vary by timing of surgery relative to both menopause and age. PMID- 27183049 TI - Precise, Self-Limited Epitaxy of Ultrathin Organic Semiconductors and Heterojunctions Tailored by van der Waals Interactions. AB - Precise assembly of semiconductor heterojunctions is the key to realize many optoelectronic devices. By exploiting the strong and tunable van der Waals (vdW) forces between graphene and organic small molecules, we demonstrate layer-by layer epitaxy of ultrathin organic semiconductors and heterostructures with unprecedented precision with well-defined number of layers and self-limited characteristics. We further demonstrate organic p-n heterojunctions with molecularly flat interface, which exhibit excellent rectifying behavior and photovoltaic responses. The self-limited organic molecular beam epitaxy (SLOMBE) is generically applicable for many layered small-molecule semiconductors and may lead to advanced organic optoelectronic devices beyond bulk heterojunctions. PMID- 27183050 TI - Anything is Possible. PMID- 27183051 TI - Food Guide Follies. PMID- 27183052 TI - Taxation and Sugar-Sweetened Beverages: Position of Dietitians of Canada. AB - Dietitians of Canada recommends that an excise tax of at least 10-20% be applied to sugar-sweetened beverages sold in Canada given the negative impact of these products on the health of the population and the viability of taxation as a means to reduce consumption. For the greatest impact, taxation measures should be combined with other policy interventions such as increasing access to healthy foods while decreasing access to unhealthy foods in schools, daycares, and recreation facilities; restrictions on the marketing of foods and beverages to children; and effective, long-term educational initiatives. This position is based on a comprehensive review of the literature. The Canadian population is experiencing high rates of obesity and excess weight. There is moderate quality evidence linking consumption of sugar-sweetened beverages to excess weight, obesity, and chronic disease onset in children and adults. Taxation of sugar sweetened beverages holds substantiated potential for decreasing its consumption. Based on economic models and results from recent taxation efforts, an excise tax can lead to a decline in sugar-sweetened beverage purchase and consumption. Taxation of up to 20% can lead to a consumption decrease by approximately 10% in the first year of its implementation, with a postulated 2.6% decrease in weight per person on average. Revenue generated from taxation can be used to fund other obesity reduction initiatives. A number of influential national organizations support a tax on sugar-sweetened beverages. PMID- 27183053 TI - Effects of Peripapillary Scleral Stiffening on the Deformation of the Lamina Cribrosa. AB - PURPOSE: Scleral stiffening has been proposed as a treatment for glaucoma to protect the lamina cribrosa (LC) from excessive intraocular pressure-induced deformation. Here we experimentally evaluated the effects of moderate stiffening of the peripapillary sclera on the deformation of the LC. METHODS: An annular sponge, saturated with 1.25% glutaraldehyde, was applied to the external surface of the peripapillary sclera for 5 minutes to stiffen the sclera. Tissue deformation was quantified in two groups of porcine eyes, using digital image correlation (DIC) or computed tomography imaging and digital volume correlation (DVC). In group A (n = 14), eyes were subjected to inflation testing before and after scleral stiffening. Digital image correlation was used to measure scleral deformation and quantify the magnitude of scleral stiffening. In group B (n = 5), the optic nerve head region was imaged using synchrotron radiation phase-contrast microcomputed tomography (PC MUCT) at an isotropic spatial resolution of 3.2 MUm. Digital volume correlation was used to compute the full-field three-dimensional deformation within the LC and evaluate the effects of peripapillary scleral cross linking on LC biomechanics. RESULTS: On average, scleral treatment with glutaraldehyde caused a 34 +/- 14% stiffening of the peripapillary sclera measured at 17 mm Hg and a 47 +/- 12% decrease in the maximum tensile strain in the LC measured at 15 mm Hg. The reduction in LC strains was not due to cross linking of the LC. CONCLUSIONS: Peripapillary scleral stiffening is effective at reducing the magnitude of biomechanical strains within the LC. Its potential and future utilization in glaucoma axonal neuroprotection requires further investigation. PMID- 27183055 TI - A pH-activatable nanoparticle with signal-amplification capabilities for non invasive imaging of tumour malignancy. AB - Engineered nanoparticles that respond to pathophysiological parameters, such as pH or redox potential, have been developed as contrast agents for the magnetic resonance imaging (MRI) of tumours. However, beyond anatomic assessment, contrast agents that can sense these pathological parameters and rapidly amplify their magnetic resonance signals are desirable because they could potentially be used to monitor the biological processes of tumours and improve cancer diagnosis. Here, we report an MRI contrast agent that rapidly amplifies magnetic resonance signals in response to pH. We confined Mn(2+) within pH-sensitive calcium phosphate (CaP) nanoparticles comprising a poly(ethylene glycol) shell. At a low pH, such as in solid tumours, the CaP disintegrates and releases Mn(2+) ions. Binding to proteins increases the relaxivity of Mn(2+) and enhances the contrast. We show that these nanoparticles could rapidly and selectively brighten solid tumours, identify hypoxic regions within the tumour mass and detect invisible millimetre-sized metastatic tumours in the liver. PMID- 27183054 TI - Objective Measurement of Fusional Vergence Ranges and Heterophoria in Infants and Preschool Children. AB - PURPOSE: Binocular alignment typically includes motor fusion compensating for heterophoria. This study evaluated heterophoria and then accommodation and vergence responses during measurement of fusional ranges in infants and preschoolers. METHODS: Purkinje image eye tracking and eccentric photorefraction (MCS PowerRefractor) were used to record the eye alignment and accommodation of uncorrected infants (n = 17; 3-5 months old), preschoolers (n = 19; 2.5-5 years), and naive functionally emmetropic adults (n = 14; 20-32 years; spherical equivalent [SE], +1 to -1 diopters [D]). Heterophoria was derived from the difference between monocular and binocular alignments while participants viewed naturalistic images at 80 cm. The presence or absence of fusion was then assessed after base-in (BI) and base-out (BO) prisms (2-40 prism diopters [pd]) were introduced. RESULTS: Mean (+/-SD) SE refractions were hyperopic in infants (+2.4 +/- 1.2 D) and preschoolers (+1.1 +/- 0.6 D). The average exophoria was similar (P = 0.11) across groups (Infants, -0.79 +/- 2.5 pd; Preschool, -2.43 +/- 2.0 pd; Adults, -1.0 +/- 2.7 pd). Mean fusional vergence range also was similar (P = 0.1) for BI (Infants, 11.2 +/- 2.5 pd; Preschool, 8.8 +/- 2.8 pd; Adults, 11.8 +/- 5.2 pd) and BO (Infants, 14 +/- 6.6 pd; Preschool, 15.3 +/- 8.3 pd; Adults, 20 +/- 9.2 pd). Maximum change in accommodation to the highest fusible prism was positive (increased accommodation) for BO (Infants, 1.69 +/- 1.4 D; Preschool, 1.35 +/- 1.6 D; Adults, 1.22 +/- 1.0 D) and negative for BI (Infants, -0.96 +/- 1.0 D; Preschool, -0.78 +/- 0.6 D; Adults, -0.62 +/- 0.3 D), with a similar magnitude across groups (BO, P = 0.6; BI, P = 0.4). CONCLUSIONS: Despite typical uncorrected hyperopia, infants and preschoolers exhibited small exophorias at 80 cm, similar to adults. All participants demonstrated substantial fusional ranges, providing evidence that even 3- to 5-month-old infants can respond to a large range of image disparities. PMID- 27183056 TI - Atomic force microscopy as a tool to evaluate the risk of cardiovascular diseases in patients. AB - The availability of biomarkers to evaluate the risk of cardiovascular diseases is limited. High fibrinogen levels have been identified as a relevant cardiovascular risk factor, but the biological mechanisms remain unclear. Increased aggregation of erythrocytes (red blood cells) has been linked to high plasma fibrinogen concentration. Here, we show, using atomic force microscopy, that the interaction between fibrinogen and erythrocytes is modified in chronic heart failure patients. Ischaemic patients showed increased fibrinogen-erythrocyte binding forces compared with non-ischaemic patients. Cell stiffness in both patient groups was also altered. A 12-month follow-up shows that patients with higher fibrinogen-erythrocyte binding forces initially were subsequently hospitalized more frequently. Our results show that atomic force microscopy can be a promising tool to identify patients with increased risk for cardiovascular diseases. PMID- 27183057 TI - Stochastic phase-change neurons. AB - Artificial neuromorphic systems based on populations of spiking neurons are an indispensable tool in understanding the human brain and in constructing neuromimetic computational systems. To reach areal and power efficiencies comparable to those seen in biological systems, electroionics-based and phase change-based memristive devices have been explored as nanoscale counterparts of synapses. However, progress on scalable realizations of neurons has so far been limited. Here, we show that chalcogenide-based phase-change materials can be used to create an artificial neuron in which the membrane potential is represented by the phase configuration of the nanoscale phase-change device. By exploiting the physics of reversible amorphous-to-crystal phase transitions, we show that the temporal integration of postsynaptic potentials can be achieved on a nanosecond timescale. Moreover, we show that this is inherently stochastic because of the melt-quench-induced reconfiguration of the atomic structure occurring when the neuron is reset. We demonstrate the use of these phase-change neurons, and their populations, in the detection of temporal correlations in parallel data streams and in sub-Nyquist representation of high-bandwidth signals. PMID- 27183058 TI - Phase-change devices: Crystal-clear neuronal computing. PMID- 27183059 TI - Comparison and evaluation of pesticide monitoring programs using a process-based mixture model. AB - A number of European countries run large-scale pesticide monitoring schemes in watersheds aimed at identifying and evaluating the presence of pesticide residues in the environment. These schemes provide national and regional scale assessments of pesticide concentrations within the context of environmental quality assessment, aiming to ensure some degree of ecological protection. The present study is aimed at evaluating the joint effects of the pesticide mixtures detected in monitoring programs, using a process-based mixture model that was parameterized for Daphnia magna. In total, over 15 000 samples containing over 1 million individual measurements were evaluated for effects. It was found that there are only a small number of places where one can expect to have effects on daphnids, based on measured concentrations. The most polluted samples would cause extinction of a daphnid population within only 30 h. The results show that effects are mostly triggered by a limited number of pesticide residues at locations with high emissions. It was also shown that the analytical detection limits are basically too high to exclude mixture effects. So, despite all the effort that is put into chemical monitoring programs, it remains a challenge to make statements on whether or not the environment is protected. Recommendations are offered for a different setup of monitoring programs to improve this situation. Environ Toxicol Chem 2016;35:3113-3123. (c) 2016 SETAC. PMID- 27183060 TI - Effect of Single Off-Axis Implant Placement on Abutment Screw Stability Under Lateral Loading. AB - PURPOSE: The aim of this study was to evaluate the effect of off-axis implant placement in relation to the prosthetic crown on abutment screw loosening under different directions of twisting moments. MATERIALS AND METHODS: Twenty-one implant assemblies were divided equally into three groups (n = 7). Each assembly consisted of an internal-octagon implant measuring 4.1 * 12 mm (standard plus implants) with corresponding 5.5-mm synocta abutments (Straumann) mounted in an epoxy resin-glass fiber composite. Group A had a straight implant configuration in relation to the prosthetic crown and was subjected to clockwise twisting moment (control). The other two groups, B and C, with off-axis implant placement were subjected to clockwise and counterclockwise moments, respectively. A lateral load of 80 N was applied to the specimens for 1 * 10(6) cycles at 90 degrees to the long axis of the implant. The loading point was 4 mm from the center of the implant in group A and 6 mm in groups B and C. The reverse torque value (RTV) of the abutment screw was measured before and after loading. Data were analyzed using a paired samples t test and one-way analysis of variance (ANOVA) at a significance level of alpha = .05. RESULTS: An increase in postloading RTV was found relative to preloading RTV in all groups, but was only significant in group A (P < .05). The mean reverse torque difference (RTD) was higher in group A (3.17 +/- 1.04 Ncm), followed by groups B (1.03 +/- 1.41 Ncm) and C (0.43 +/- 1.09 Ncm). A significant difference in RTD was noted between group A and the remaining groups (P < .05). However, no significant difference was found between groups B and C (P > .05). CONCLUSION: Placement of an implant in an off-axis relation to the prosthetic crown resulted in significantly lower reverse torque values compared with straight implant configuration. However, the extent of reduction in Ncm is small and is considered clinically insignificant in the studied implant system. Furthermore, no significant difference was found in RTV between clockwise and counterclockwise twisting moments. PMID- 27183061 TI - Cone Beam Computed Tomography vs Multislice Computed Tomography in Computer-Aided Design/Computer-Assisted Manufacture Guided Implant Surgery Based on Three Dimensional Optical Scanning and Stereolithographic Guides: Does Image Modality Matter? AB - PURPOSE: Cone beam computed tomography (CBCT) is increasingly overtaking multislice computed tomography (MSCT) for implant planning and computer-aided design/computer-assisted manufacturing (CAD/CAM) surgical guide fabrication. The purpose of this study was to evaluate whether the image modality has a significant influence on the accuracy of image-fusion stereolithographic guides. MATERIALS AND METHODS: A total of 240 implants were placed in 30 polymer models using surgical guides fabricated using CBCT or MSCT and optical scanning of dental casts and diagnostic wax-up. Postsurgical image data were fused with the planning data for evaluation of the following errors: total error (Euclidean error), mesiodistal and buccolingual error, depth error, and angular error. The CBCT and MSCT results were statistically compared using a t test (P = .05). RESULTS: CBCT showed a statistically significantly higher total error with mean (+/- SD) of 0.36 +/- 0.13 mm vs 0.27 +/- 0.13 mm (P = .000), mesiodistal error with 0.20 +/- 0.14 mm vs 0.16 +/- 0.11 mm (P = .018), and depth error with 0.17 +/- 0.12 mm vs 0.07 +/- 0.07 mm (P = .000). Buccolingual and angular errors did not statistically significantly differ with 0.16 +/- 0.11 mm vs 0.15 +/- 0.12 mm (P = .613), and 0.96 +/- 0.47 degrees vs 0.85 +/- 0.59 degrees (P = .111). CONCLUSION: Using CBCT for image-fusion stereolithographic guides may provide lower accuracy than MSCT. The results should be confirmed on alternative CBCT scanners. Due to the total volume of tissues, image artifacts, and patient movements, the advantages seen using MSCT on models could be nonexistent or exacerbated on patients. Patient studies are required to demonstrate clinical relevance. PMID- 27183062 TI - Feasibility of Dental Implant Replacement in Failed Sites: A Systematic Review. AB - PURPOSE: To assess the clinical outcomes of replaced implants after removal of failed ones. In addition, associated risk factors that might affect the final outcome of these procedures were also explored. MATERIALS AND METHODS: An electronic literature search was conducted by two reviewers in several databases for articles written in English up to November 2014. Human clinical trials with a minimum of 10 subjects enrolled that reported clinical outcomes with a mean follow-up period of at least 12 months after implant replacement were included. Implant survival and nonmodifiable/modifiable factors at second and third implant placement attempts were studied. Hence, the PICO question that was aimed to be addressed was: Do patients undergoing implant replacement (second and third attempts) in previous failed sites have comparable clinical outcomes by means of implant survival/failure rate to implants placed at the first attempt? RESULTS: Five retrospective clinical cohort studies and two case series satisfied the selection criteria and thus were included in this review. In total, 396 patients were studied due to implant replacement in previous failed sites. The survival rate for implant replacement at the second attempt was 88.84% (390/439; range, 71% to 94.6%) with a mean follow-up of 41.59 +/- 16.77 months. Thirty-one implants were replaced for a third attempt with a mean survival rate of 74.19% (23/31) at the follow-up of 29.66 +/- 14.71 months. Major risk indicators were generally divided into patient-related factors (health status, smoking habits, and oral hygiene maintenance), implant characteristics (dimensions, coating, and loading), and site characteristics (bone quality and density, vertical and horizontal dimensions, soft tissue around the implant). CONCLUSION: Implant replacement is a reasonably feasible option for scenarios of early and late implant failure. However, modifiable risk factors must be controlled before proceeding for implant replacement. PMID- 27183063 TI - Titanium-Zirconium Binary Alloy as Dental Implant Material: Analysis of the Influence of Compositional Change on Mechanical Properties and In Vitro Biologic Response. AB - PURPOSE: To evaluate the mechanical properties and biologic response of single phase Ti-Zr alloys cast in higher-purity casting conditions, with comprehensive compositions (from 10 to 90 mol% of Zr). MATERIALS AND METHODS: The mechanical properties and in vitro biologic response with proportional increase of Zr to Ti Zr alloy composition were assessed. Tensile strength, surface hardness, and Young's modulus were examined. The in vitro cell response of the alloys was also tested with mouse osteoblast cells. RESULTS: Analyses of mechanical tests demonstrated improved strength and reduced Young's modulus on this binary alloy system. In vitro cell culture studies with osteogenic MCT3T-E1 cells exhibited the highest attachment rate with the largest and more mature cells on Ti10Zr, instead of commercially pure Ti, whereas a significantly lower cell attachment rate and delayed alkaline phosphatase-specific activity (ALP) differentiation were detected on Ti50Zr. CONCLUSION: The results revealed that the composition did have an impact on the in vitro biologic response. Ti-Zr alloys with 50-50 mol% composition had a decreased biologic response, although the mechanical properties improved. The overall highest strength was Ti with 30 mol% Zr without significant decrease of biologic response. PMID- 27183064 TI - Comparison of Oxygen Plasma Treatment and Sandblasting of Titanium Implant Abutment Surface on Bond Strength and Surface Topography. AB - PURPOSE: This in vitro study was designed to compare the effects of oxygen plasma and sandblasting treatment of the surface of titanium implant abutments on retention of implant-supported fixed prostheses using eugenol-free provisional cement and surface topography. Cement failure mode and elemental composition were surveyed. MATERIALS AND METHODS: Thirty implant abutments were used. They were divided into three groups (n = 10 implants) according to the surface treatment made (no treatment, sandblasting with 50 MUm Al2O3, and oxygen plasma). Thirty metal copings were fabricated with an occlusal metal O-ring and cemented using eugenol-free cement. The tensile bond strength was recorded using a universal testing machine, cement failure was recorded, surface topography was determined using the optical method, and elemental composition was determined using energy dispersive x-ray spectroscopy. Data from all the groups were compared with a one way analysis of variance (ANOVA; P < .05) and Tukey test. RESULTS: The mean values of tensile bond strength of metal copings bonded to three implant-abutment surface groups with either control, sandblasting, or oxygen plasma were 138.8 +/- 10.2, 261.3 +/- 20.6, and 264.7 +/- 12.8 N, respectively. The cements failed adhesively in the control and oxygen plasma groups and cohesively for sandblasting. The mean values of surface roughness were 1.1 +/- 0.2, 2.3 +/- 0.5, and 1.0 +/- 0.1, respectively. The oxygen plasma-treated group evidenced a decreased level of C and increased levels of O2. CONCLUSION: The retention of cast crown copings to titanium implant abutments using eugenol-free provisional cement in the sandblasting and oxygen plasma groups was more improved than in the control group. PMID- 27183065 TI - Transfer of Bacteria into the Internal Cavity of Dental Implants After Application of Disinfectant or Sealant Agents In Vitro. AB - PURPOSE: Bacterial colonization of the inner part of dental implants has been reported in numerous studies. The aim of this in vitro study was to analyze the bacterial colonization of the implant lumen of two implant systems that were partly subjected to a thermal cycling regimen after three different approaches to reducing bacterial load: filling of the hollow parts with either a disinfectant agent, a setting sealing compound, or a nonsetting sealing compound. MATERIALS AND METHODS: Two implant systems with internal connections (the Bego Semados RI implant, Bego, and the Xive S Plus Screw Implant, Dentsply) were used in this study. Before the corresponding abutments were fixed, the internal cavities were pretreated in four different ways (application of a 0.2% chlorhexidine gel, a special silicone, or a sealing grease, or no pretreatment). Half of the specimens were subjected to thermocycling. After incubation of the assemblies in a bacterial suspension of Escherichia coli for 1 week, the abutments were removed, and microbial samples of the internal aspects were collected; contamination was evaluated with quantitative realtime polymerase chain reaction (PCR). RESULTS: No pretreatment could hinder bacterial leakage in all cases, but all applied agents could reduce bacterial burden significantly (P < .05). There was less bacterial colonization after thermocycling (P < .05), and the Xive implants showed better resistance against microbial contamination (P < .05). CONCLUSION: The application of products to reduce bacterial invasion can help reduce bacterial load to a minimum and therefore can be helpful in minimizing the cofactors that contribute to the development of peri-implantitis. PMID- 27183066 TI - Hydroxyapatite Dome for Bone Neoformation in Rabbit Tibia. AB - PURPOSE: To evaluate supracortical bone neoformation with the use of hydroxyapatite (HA) hollow domes specially manufactured for osteogenesis promotion. MATERIALS AND METHODS: Nine New Zealand rabbits were selected and 18 domes were placed, divided into three groups according to the filler: control (blood clot), vitamin complex, and particulate beta-tricalcium phosphate (beta TCP). The healing period was 8 weeks, hence fluorescent markers were applied. After healing, the samples were embedded in resin to prepare slides for light and fluorescence microscopic evaluation of the amount of neoformed bone tissue. Energy dispersive spectroscopy was also used for chemical analysis of the material inside the domes. RESULTS: The quality of neoformed bone tissue with active bone remodeling areas was observed. As a filler, beta-TCP showed higher bone formation (14.1%), better quality of neoformed bone tissue with organized structures, and an area of mineralized tissue in the dome. Bone neoformation inside the dome filled with blood clot confirmed the osteoconductive property of HA, as indicated by the migration of osteogenic cells from the blood clot, without the action of another biomaterial (mean area of bone formation for blood clot filler = 7.5%). Bone neoformation was not favored in samples filled with vitamin complex because of the difficulty of blood penetration through the material. CONCLUSION: HA domes performed well as a scaffold for bone neoformation over the cortical bone of rabbits, and this is based on maintenance of good stability and good integration with bone tissue. beta-TCP presented higher values of neoformed bone area compared with the blood clot. HA domes have osteoconductive properties, especially when filled with blood clot, because of the migration of osteogenic cells without action of any other biomaterial. In domes filled with vitamin complex, no bone formation was noted because of the absence of resorption. PMID- 27183067 TI - Comparison of Guided Bone Regeneration Between Surface-Modified and Pristine Titanium Membranes in a Rat Calvarial Model. AB - PURPOSE: The objectives of this study were to evaluate bioactivity of a titanium membrane with anodization, cyclic precalcification, and heat (APH) treatment (APHTM), and to compare APHTM and nontreated titanium membrane (NTTM) in guided bone regeneration using histologic analysis and microcomputed tomography (micro CT). MATERIALS AND METHODS: APHTM samples were prepared and immersed in simulated body fluid for 2 days, then observed using field-emission scanning electron microscopy, followed by an analysis of calcium and phosphate precipitation using an energy dispersive x-ray spectroscopy. For the in vivo experiment, critical size defects were created in rat calvaria (diameter, 8 mm) and treated with either APHTM or NTTM (n = 14 each). Biopsies were performed at 2 and 4 weeks for histologic analysis (n = 3 per group each time). Fluorochrome bone markers were injected in three rats in each group at 3 (alizarin red) and 5 weeks (calcein green), followed by histologic examination at 7 weeks. Micro-CT was performed at 8 weeks (n = 5 per group). RESULTS: APHTM exhibited high bioactivity, characterized by dense nano-sized flakelike crystals throughout the membrane and an increase in the calcium-phosphate concentrations after 2-day immersion in simulated body fluid. At 2 and 4 weeks, APHTM samples showed an intimate bone formation onto the membrane, whereas NTTM samples demonstrated interposition of connective tissue between the membrane and newly formed bone. The same pattern was found in the fluorescent study. The micro-CT analysis revealed significantly lower bone volume but higher bone mineral density in the APHTM samples than in the NTTM samples (P < .05). CONCLUSION: The results suggest that APH treatment on titanium membrane promotes intimate bone formation toward the membrane, thus increasing structural durability for bone regeneration. Further research is warranted to confirm the results found in these in vitro and in vivo experiments. PMID- 27183069 TI - Fatigue Behavior of Computer-Aided Design/Computer-Assisted Manufacture Ceramic Abutments as a Function of Design and Ceramics Processing. AB - PURPOSE: Zirconia is being widely used, at times apparently by simply copying a metal design into ceramic. Structurally, ceramics are sensitive to both design and processing (fabrication) details. The aim of this work was to examine four computer-aided design/computer-assisted manufacture (CAD/CAM) abutments using a modified International Standards Organization (ISO) implant fatigue protocol to determine performance as a function of design and processing. MATERIALS AND METHODS: Two full zirconia and two hybrid (Ti-based) abutments (n = 12 each) were tested wet at 15 Hz at a variety of loads to failure. Failure probability distributions were examined at each load, and when found to be the same, data from all loads were combined for lifetime analysis from accelerated to clinical conditions. RESULTS: Two distinctly different failure modes were found for both full zirconia and Ti-based abutments. One of these for zirconia has been reported clinically in the literature, and one for the Ti-based abutments has been reported anecdotally. The ISO protocol modification in this study forced failures in the abutments; no implant bodies failed. Extrapolated cycles for 10% failure at 70 N were: full zirconia, Atlantis 2 * 10(7) and Straumann 3 * 10(7); and Ti based, Glidewell 1 * 10(6) and Nobel 1 * 10(21). Under accelerated conditions (200 N), performance differed significantly: Straumann clearly outperformed Astra (t test, P = .013), and the Glidewell Ti-base abutment also outperformed Atlantis zirconia at 200 N (Nobel ran-out; t test, P = .035). CONCLUSION: The modified ISO protocol in this study produced failures that were seen clinically. The manufacture matters; differences in design and fabrication that influence performance cannot be discerned clinically. PMID- 27183068 TI - Long-Term Survival Rates of Titanium Implants Placed in Expanded Alveolar Ridges Using Split Crest Procedures: A Systematic Review. AB - PURPOSE: To evaluate the survival rates of titanium dental implants placed using split crest procedures for alveolar ridge expansion. MATERIALS AND METHODS: The MEDLINE, CENTRAL, and OpenGrey databases were searched up to January 2015 for studies assessing implants that had been placed in areas submitted to split crest procedures. Two methodologic quality-assessment tools were used based on the type of study. For randomized controlled trials (RCTs), the Cochrane Collaboration tool was used to assess the risk of bias. For the observational studies, an adapted version of the Newcastle-Ottawa scale was used. RESULTS: A total of 1,178 patients received 3,033 implants with ridge expansion. On average, the success rate was 96.6% and the survival rate was 96.8%, with a mean follow-up of 58.3 months. Six of the nine included studies used a bone substitute associated or not with a membrane, and seven studies used an implant in both the maxilla and mandible. In addition, half of the observational studies were considered to be of medium quality, whereas the others were considered to be of low quality; the sole RCT included was classified as having a high risk of bias. CONCLUSION: The use of split crest techniques appears to provide predictable alveolar ridge augmentation as well as high survival rates in the short and long term for implants placed in the maxilla or mandible. Patients must be selected with caution. PMID- 27183070 TI - Evaluation of a Reverse-Tapered Design on the Osseointegration of Narrow-Diameter Implants in Beagle Dogs: A Pilot Study. AB - PURPOSE: The purpose of this study was to evaluate a reverse-tapered design on the osseointegration of narrow-diameter implants in comparison with a conventional tapered design in beagle dogs. MATERIALS AND METHODS: All mandibular premolars and first molars were extracted bilaterally in four beagle dogs. Three months later, three kinds of implants were placed in both quadrants of the mandible: tapered narrow-diameter implants processed by cold working (TNC; n = 8), reverse-tapered narrow-diameter implants (RTN; n = 8), and reverse-tapered narrow-diameter implants processed by cold working (RTNC; n = 8). The animals were sacrificed at 4 weeks. Implant stability quotient (ISQ) values were measured at the time of implant placement and sacrifice. Histomorphometric analysis was performed. RESULTS: The baseline ISQ values were significantly lower in the RTN (56.0 +/- 11.6) and RTNC (57.2 +/- 9.8) than in the TNC (68.0 +/- 5.4; P = .021). At 4 weeks, the TNC (69.9 +/- 5.1) exhibited significantly higher ISQ values compared with the RTNC (61.6 +/- 4.1; P = .024). Histologic analysis in the RTN and RTNC revealed osseointegration without any signs of inflammation; however, unresolved coronal gap or dehiscence was also observed. The total bone-to-implant contact ratios (BIC) in TNC, RTN, and RTNC were 55.1% +/- 11.5%, 47.8% +/- 19.1%, and 60.2% +/- 15.3%, respectively, and no significant differences were shown among them. The BIC for the coronal part in each group was 51.1% +/- 29.4%, 28.8% +/- 33.8%, and 23.9% +/- 23.3%, respectively, and the differences were not significant. In the threaded part, TNC, RTN, and RTNC showed a BIC of 56.3% +/- 9.6%, 50.7% +/- 18.3%, and 65.3% +/- 15.6%, respectively. There was no significant difference among them. CONCLUSION: The reverse-tapered design on narrow-diameter implants showed a lower initial stability than the conventional tapered design; however, there was equivalent osseointegration in an early healing phase. PMID- 27183071 TI - A New Method Using Autogenous Impacted Third Molars for Sinus Augmentation to Enhance Implant Treatment: Case Series with Preliminary Results of an Open, Prospective Longitudinal Study. AB - PURPOSE: This prospective longitudinal study reports on the results in patients given autologous tooth material for augmentation in a sinus elevation procedure. MATERIALS AND METHODS: Six patients with inadequate bone supply for augmentation in the maxillary posterior tooth region and at least one impacted maxillary third molar underwent sinus elevation surgery with lateral access using the particulate tooth material. One of the patients received four implants during the same session, while the other patients had a total of 15 implants placed after a healing phase of an average 5.5 months. Drill cylinders collected from the implant bed during the procedure were subjected to histologic/immunohistochemical evaluation. RESULTS: All six patients showed normal and unobtrusive postoperative healing, having undergone prosthetic restoration up to 5 years before. The average peri-implant probing pocket depth after a period of up to 5 years ranged between 1.86 mm (mesial and lingual) and 2.07 mm (distal and buccal). No bleeding could be triggered with any of the peri-implant probes. The average peri-implant bone resorption measured during the first year was up to 0.63 mm, with the lowest being 0 mm and the maximum 2.9 mm. Peri-implant bone remained stable for the follow-up time of up to 5 years. Histologically, six biopsy specimens collected from five patients showed osteoconductive osteogenesis with encapsulation of tooth enamel and dentin portions and partial resorption of the tooth components. Cementum shares were no longer discernible. Immunohistochemical assessment showed intense new vessel formation that could be observed in the area of loose stroma of reorganized tissue in the augmented area. CONCLUSION: Within the limits of these preliminary results and with adequate consideration of the small number of patients included, the use of autogenous crushed tooth material from impacted third molars may represent an alternative augmentation material for use in sinus elevation procedures. PMID- 27183073 TI - Marginal Bone Stability Around Tapered, Platform-Shifted Implants Placed with an Immediately Loaded Four-Implant-Supported Fixed Prosthetic Concept: A Cohort Study. AB - PURPOSE: To longitudinally evaluate marginal bone remodeling around tapered, platform-shifted implants placed for total arch rehabilitation with fixed hybrid prostheses. MATERIALS AND METHODS: A retrospective cohort study was designed that evaluated radiographic data from patients undergoing implant surgical procedures with an immediately loaded four-implant-supported fixed prosthetic concept in a single clinic setting during a 36-month period. The primary outcome variable was the change in marginal bone levels during a 12- to 36-month follow-up postloading with the definitive prosthesis. All measurements were performed on matched and calibrated periapical radiographs obtained at: (1) the time of placement of the definitive prosthesis (baseline) versus (2) 12 to 36 months following definitive loading (follow-up). Other study variables, including duration of follow-up, implant position, maximum insertion torque, implant angulation, and implant diameter, were assessed for their association with changes in marginal bone levels. RESULTS: One hundred sixty-nine patients (n = 856 implants) with a mean age of 59.5 +/- 10.5 years were included in this study. Two implants failed, resulting in a 99.8% overall survival rate (mean follow-up: 15.2 +/- 4.8 months, range: 12 to 36 months). The radiographic mean bone levels at baseline and follow up were 1.16 +/- 0.71 mm (n = 805) and 1.31 +/- 0.93 mm (n = 805), respectively. The mean marginal bone loss from baseline to follow-up was 0.14 +/- 0.59 mm (n = 805). The duration of follow-up had no effect on the extent of marginal bone loss (P = .154). CONCLUSION: Within the limitations of this large-scale retrospective cohort study, it was concluded that the use of tapered, platform-shifted implants for total arch rehabilitation with the use of the All-on-Four protocol yields very favorable radiographic outcomes, at least after a minimum of 12 months in function. PMID- 27183072 TI - Soft Tissue Response in Posterior Teeth Adjacent to Interdental Single Implants: A Controlled Randomized Clinical Trial Comparing Intrasulcular vs Trapezoidal Incision. AB - PURPOSE: To evaluate the soft tissue response in posterior teeth adjacent to interdental single implants comparing intrasulcular and trapezoidal incision, and to study their evolution over time. MATERIALS AND METHODS: A controlled randomized clinical trial was carried out in the Oral Surgery and Implantology Unit of a University Clinic. All the included patients received an interdental single implant (Frontier 2.45, Ilerimplant; Global Medical Implants). The incision type was randomized by sealed envelopes into two groups using the SPSS statistical package (SPSS): (1) intrasulcular or (2) trapezoidal incision. Probing depth and gingival recession at the mesial and distal teeth adjacent to the implant were measured before implant placement, 1 month after surgery, the day of the abutment connection, and at 6 months and 1 year postloading. Scar formation and papilla index were measured 1 month after surgery, and at 6 months and 1 year postloading. RESULTS: Forty patients with one implant per patient were included: 20 in the intrasulcular and 20 in the trapezoidal group. No statistical differences were found between incision types in the measured parameters (probing depth, recession, and interproximal papilla). When analyzing periodontal changes of the total sample, significant differences were found between implant placement and the 1-year follow-up in recession, scar formation, and papilla index. CONCLUSION: The incision type used to place a single interdental implant did not significantly influence the periodontal parameters of the adjacent teeth. Considering the whole sample, the values between implant placement and 1 year postloading showed significant differences in recession, scar formation, and papilla index over time. PMID- 27183074 TI - Patient-Perceived Morbidity and Subjective Functional Impairment Following Immediate Transition from a Failing Dentition to Fixed Implant Rehabilitation. AB - PURPOSE: Failing residual dentition gives rise to patient concerns about the surgical and prosthodontic management of immediate implant rehabilitation. The purpose of this study was to assess subjective patient experiences of full-arch immediate implant loading. MATERIALS AND METHODS: Patients made a transition from poor dentition in the maxilla (25 patients) or mandible (25 patients) to full arch rehabilitation on the day of extraction using four interantral or interforaminal implants. Provisional restoration was performed, and postoperative pain, swelling, and patient-perceived impairment in the first week was recorded. RESULTS: Absence of pain was reported by 40%, 52%, and 66% of patients, on the day of surgery, on the first day after surgery, and on the second day after surgery, respectively; pain levels decreased significantly (from 1.8 to 0.9, P < .001) and patient-reported swelling decreased from 1.5 to 1.3 (P = .058) on a 10 point scale. Postoperative impairment of everyday life and work (mean score = 1.1) was significantly less pronounced than impairment of food intake (mean score = 2.2; P = .004) or speech (mean score = 1.9; P = .002). Of these patients, 88% would again undergo the procedure without doubt. CONCLUSION: Although patient perceived morbidity after immediate full-arch implant rehabilitation is low in general, minor masticatory and phonetic impairment should be taken into account. PMID- 27183075 TI - A Long-Term Prospective Evaluation of Marginal Bone Level Change Around Different Implant Systems. AB - PURPOSE: The purpose of this prospective study was to assess the change of marginal bone level around three different types of external-hex implants after 5 years using radiography. MATERIALS AND METHODS: Included in this study were 54 patients randomly put into three different groups; rough-surface implants (Branemark), machined coronal aspect implants (Restore), and microthreaded coronal aspect implants (Hexplant). Clinical and radiographic assessments were performed contemporaneously with implant loading (baseline) and at 1, 3, and 5 years post-functional loading. A mixed-model analysis was employed to examine mean marginal bone change significance in the three treatment groups. RESULTS: In a total of 31 out of 54 patients, 81 of 135 implants remained to the end of the study. At 5 years, the microthreaded coronal aspect implants had 0.61 +/- 0.32 mm mean crestal bone loss; the rough-surface implants without microthread, 0.99 +/- 0.38 mm; and the machined coronal aspect implants, 1.06 +/- 0.39 mm. The rough surface implants and the machined coronal aspect implants did not exhibit statistically significantly different marginal bone loss, whereas the microthreaded coronal aspect implants exhibited significantly less marginal bone loss (P = .0015). CONCLUSION: In this research, rough-surface implants with microthreads showed positive long-term effects in preserving peri-implant bone level against functional loads when compared with implants lacking these aspects at the coronal part. Most of the bone loss was shown within 1 year of loading, and all types of implants stabilized after 1 year. PMID- 27183076 TI - Bone Volume Changes After Sinus Floor Augmentation with Heterogenous Graft. AB - PURPOSE: The aim of this study was to evaluate the volumetric stability of deproteinized bovine bone after sinus augmentation, using cone beam computed tomography (CBCT) and three-dimensional (3D) analysis. MATERIALS AND METHODS: Using a specific selection tool and 3D reconstruction from InVesalius 3.0, volumetric analysis of CBCT scans was performed in patients undergoing a sinus elevation technique in critical defects, using deproteinized bovine bone. The first scan was performed immediately after graft surgery (T1), and the second was performed 8 months after graft surgery (T2). RESULTS: A total of 13 patients met the inclusion criteria of this retrospective study; 26 postoperative CBCT scans were analyzed for these patients. All patients exhibited an increase in bone volume (9.10%). The mean bone volume increase from T1 to T2 was 0.137 cm(3) (SD: +/- 0.104 cm(3)). There was a statistically significant correlation between bone volume and time (P < .0001). The mean bone volume was 1.506 cm(3) (SD: +/- 0.473 cm(3)) for T1 and 1.644 cm(3) (SD: +/- 0.506 cm(3)) for T2. CONCLUSION: Within the limited sample, the study demonstrated an increase in graft volume after sinus elevation with deproteinized bovine bone in critical defects. PMID- 27183077 TI - Lateral Alveolar Ridge Expansion in the Anterior Maxilla Using Piezoelectric Surgery for Immediate Implant Placement. AB - PURPOSE: The purpose of this study was to evaluate the efficacy of the ridge splitting technique in the anterior maxilla, using piezoelectric surgery for immediate implant placement. Study outcomes were compared with those of implant placement in the same patients using the conventional drilling technique. MATERIALS AND METHODS: Ten patients received a total of 22 implants in the anterior maxilla, 11 of which were placed using a ridge-splitting procedure (test group) and the other 11 using the conventional drilling procedure (control group). Ridge width (RW), crestal bone level (BL), and implant stability quotient (ISQ) were measured at different points in time. Data were analyzed and compared between the groups using analysis of variance (ANOVA) and paired-sample t tests at a significance level of 5%. RESULTS: For the test group, the gain in RW was not stable in time because at 6 months postoperatively, the RW lost some of the initial gain; however, the net gain was still significant. At 6 months postoperatively, BL was similar for both groups. The net bone loss on the mesial aspect and the average of the mesial and the distal measures did not differ significantly between both groups. ISQ values sharply increased at 3 months postoperatively in the test group. All implants met the modified Albrektsson criteria (1989) for success. CONCLUSION: The results from this study support the efficacy and safety of ridge expansion using piezoelectric surgery for implant insertion in the anterior maxilla. The modest net gain in bone width suggests that additional hard and soft tissue augmentation may be necessary, especially in the esthetic zone. ISQ values suggest a minimum healing time of 3 months before loading the implants that have been inserted using this ridge-splitting protocol. PMID- 27183078 TI - Collagen-Coated Bovine Bone in Peri-implantitis Defects: A Pilot Study on a Novel Approach. AB - PURPOSE: As dental implants have become routine therapy, clinicians are more frequently being faced with treating peri-implantitis. To date, no single treatment protocol has been shown to be the preferred means to treat peri implantitis. The aim of this retrospective case series is to present a novel approach utilizing porcine collagen-coated bovine bone (CBB) to treat peri implantitis. MATERIALS AND METHODS: Eleven patients, with no history of periodontitis, presenting with peri-implantitis around a single restored dental implant, were included in the study. At initial and follow-up examinations, bleeding on probing (BOP), probing depth (PD), and gingival margin location (GM) were recorded. Following surgical debridement of the peri-implant defect and treatment of the implant surface with a 0.12% chlorhexidine gluconate solution, bony defects were grafted with CBB. All patients had 12 months of follow-up. RESULTS: Upon presentation, average PD at the deepest site (DS) was 7.6 +/- 1.9 mm. At the time of surgery, excess cement was found around nine implants (81%). All patients healed uneventfully without postoperative complications. At 6 and 12 months, all implants showed favorable results with average DS PD reduction of 3.9 +/- 1.5 mm and 4.1 +/- 1.6 mm, respectively. All implants showed radiographic signs of bone fill, while GM showed no changes from preoperative measurements at either 6 (0.1 +/- 0.5 mm) or 12 (0.0 +/- 0.6 mm) months. CONCLUSION: The use of a porcine collagen-coated bovine bone graft to treat peri-implantitis represents a potentially predictable therapeutic modality. Randomized controlled trials are necessary to substantiate the treatment outcomes. PMID- 27183079 TI - Anterior Maxilla Augmentation Using Palatal Bone Block with Platelet-Rich Fibrin: A Controlled Trial. AB - PURPOSE: This study was conducted to characterize clinically and radiographically the effect of using platelet-rich fibrin (PRF) autologous graft on the augmentation results of autogenous palatal bone blocks. MATERIALS AND METHODS: Patients who suffered from horizontal alveolar bone defects in the anterior maxillary ridge (<= 4.5 mm) with one or two missing teeth were augmented with autogenous palatal bone blocks 4 months prior to implant placement. PRF was used to cover the block in the test group, while only the block was used in the control. Bone width was measured with a manual caliper preaugmentation (t0), and at 0 (t1) and 4 months (t2). Cone beam computed tomography (CBCT) scans were performed at t0 and t2. Nonparametric tests (Mann-Whitney, Friedman's, and Wilcoxon signed-rank tests) were used for the comparisons. The significance level was set at P <= .05. RESULTS: In the 14 sites (12 patients), all but one autograft (from the control group) integrated successfully after 4 months. No statistically significant difference was found between demographic data in the two groups. There was a statistically significant increase in the buccopalatal bone width in both groups by time as measured by CBCT as well as the manual caliper. The test group showed statistically significantly lower mean graft resorption than the control group (test, 0.8 +/- 0.6 mm; control, 1.6 +/- 0.9 mm; P = .006). CONCLUSION: Autogenous palatal bone block surface resorption is significantly decreased by the use of PRF coverage. PMID- 27183080 TI - Three-Dimensional Nonlinear Finite Element Analysis and Microcomputed Tomography Evaluation of Microgap Formation in a Dental Implant Under Oblique Loading. AB - PURPOSE: Since bacterial leakage along the implant-abutment interface may be responsible for peri-implant infections, a realistic estimation of the interface gap width during function is important for risk assessment. The purpose of this study was to compare two methods for investigating microgap formation in a loaded dental implant, namely, microcomputed tomography (micro-CT) and three-dimensional (3D) nonlinear finite element analysis (FEA); additionally, stresses to be expected during loading were also evaluated by FEA. MATERIALS AND METHODS: An implant-abutment complex was inspected for microgaps between the abutment and implant in a micro-CT scanner under an oblique load of 200 N. A numerical model of the situation was constructed; boundary conditions and external load were defined according to the experiment. The model was refined stepwise until its load-displacement behavior corresponded sufficiently to data from previous load experiments. FEA of the final, validated model was used to determine microgap widths. These were compared with the widths as measured in micro-CT inspection. Finally, stress distributions were evaluated in selected regions. RESULTS: No microgaps wider than 13 MUm could be detected by micro-CT for the loaded implant. FEA revealed gap widths up to 10 MUm between the implant and abutment at the side of load application. Furthermore, FEA predicted plastic deformation in a limited area at the implant collar. CONCLUSION: FEA proved to be an adequate method for studying microgap formation in dental implant-abutment complexes. FEA is not limited in gap width resolution as are radiologic techniques and can also provide insight into stress distributions within the loaded complex. PMID- 27183081 TI - Influence of Palatal Coverage and Implant Distribution on Denture Strain in Maxillary Implant Overdentures. AB - PURPOSE: As maxillary implant overdentures are being increasingly used in clinical practice, prosthodontic complications related to these dentures are also reported more often. The purpose of this study was to examine the influence of palatal coverage and implant distribution on the shear strain of maxillary implant overdentures. MATERIALS AND METHODS: A maxillary edentulous model with implants inserted in the anterior, premolar, and molar areas was fabricated. Two kinds of experimental overdentures, with and without palatal coverage, were also fabricated, and two strain gauges were attached at the midline of the labial and palatal sides. A vertical occlusal load of 98 N was applied through a mandibular complete denture, and the shear strain in each denture was compared by analysis of variance (P = .05). RESULTS: In all situations, the shear strain in palateless dentures was significantly higher than in dentures with palate on both sides (P < .05). In dentures with palate, the shear strain was lower when anterior implants were present. CONCLUSION: Palateless maxillary implant overdentures exhibited much higher strain than overdentures with palate regardless of the implant distribution; this may cause more prosthodontic and implant complications. The most favorable configuration to prevent complications in maxillary implant overdentures was palatal coverage that was supported by more than four widely distributed implants. PMID- 27183083 TI - Insertion Torques of Self-Drilling Mini-Implants in Simulated Mandibular Bone: Assessment of Potential for Implant Fracture. AB - PURPOSE: Fracture of orthodontic mini-implants during insertion is a limiting factor for their clinical success. The purpose of this study was to determine the fracture potential of commonly used self-drilling orthodontic mini-implants when placed into simulated thick, dense mandibular bone. MATERIALS AND METHODS: Six mini-implant systems were assessed for the potential for fracture (Aarhus, Medicon; Dual-Top, Jeil Medical; OrthoEasy, Forestadent; tomas-pin, Dentaurum; Unitek, 3M; and VectorTAS, Ormco). First, mini-implants were inserted manually, without predrilling, into bone substitutes (Sawbones) with a 3-mm-thick, dense (1.64 g/cm(3)) cortical layer. A custom-made insertion device was used for placement of mini-implants. A sixaxis force/torque transducer was secured at the base of the bone blocks to measure the maximum torque experienced during insertion. Measured insertion torques were compared with previously reported fracture torques, yielding a torque ratio (insertion torque as a percentage of fracture torque), which was used as an indicator of the potential for mini implant fracture. Mini-implants that experienced torque ratios >= 75% upon insertion underwent further testing, following the manufacturer's recommendations for predrilling in thick, dense bone conditions. RESULTS: Significant differences in torque ratios were found among all mini-implants, except between OrthoEasy and Dual-Top, and OrthoEasy and VectorTAS. Overall, Aarhus had the highest torque ratio (91% +/- 3%), with Unitek showing the lowest ratio (37% +/- 3%). Aarhus and tomas-pin mini-implants displayed torque ratios >= 75% and experienced fracture upon insertion. When the manufacturer's specific predrilling recommendations were followed, no changes in torque ratio were found for Aarhus and tomas-pin. However, while Aarhus continued to fracture upon insertion, all tomas-pin mini implants were inserted fully without fracture following predrilling. CONCLUSION: These findings support the safe use of Unitek, VectorTAS, Dual-Top, and OrthoEasy self-drilling mini-implants in areas of 3-mm-thick, 1.64 g/cm(3) dense cortical bone without predrilling. Following predrilling, fractures did not occur with tomas-pin. For implants that continued to fracture after predrilling, other strategies may be required, such as the use of larger-diameter mini-implants in thick, dense bone conditions. PMID- 27183082 TI - Impact of Dynamic and Static Load on Bone Around Implants: An Experimental Study in a Rat Model. AB - PURPOSE: This study aimed to evaluate peri-implant bone reactions to dynamic and static loads in a rat model. MATERIALS AND METHODS: Two cylindrical titanium implants were placed in the left tibia diaphysis of 39 rats, which were divided into three groups: static load for 4 weeks (S4), static load for 8 weeks (S8), and static load for 4 weeks followed by dynamic load for 4 weeks (S4D4). All implants received a mechanical lateral load. After the experiment, the implants were extracted to determine the attachment strength around the bone and implant. The new bone formation and bone-to-implant contact were measured using plain and polarized light microscopy. RESULTS: Histologic tissue analysis revealed good contact between the bone and implant, and new bone formation around all implants. The S4D4 group had the greatest attachment strength, new bone formation, and complex collagen fiber orientation in the new bone tissue, compared with the other groups. No statistically significant differences in bone-to-implant contact were observed among the three groups. CONCLUSIONS: Applying dynamic and static loads to osseointegrated implants increased the amplification of new bone. The attachment strength was significantly improved when dynamic load was used for 4 weeks, compared with when static load was used. PMID- 27183084 TI - Analysis of Implant Strength After Implantoplasty in Three Implant-Abutment Connection Designs: An In Vitro Study. AB - PURPOSE: The aim of this in vitro study was to assess the resistance to static fatigue of implants with different connections before and after implantoplasty. MATERIALS AND METHODS: Sixty conical implants and 60 abutments were used; 4-mm diameter versions were available for each model. Three groups (n = 20) were established based on the following implant connections: external hexagon (group 1), internal hexagon (group 2), and Morse taper (group 3). The implants of each group were submitted to a compressive load before (n = 10) and after the implantoplasty (n = 10). The wear was performed in a mechanical lathe machine using a carbide bur, and the final dimensions of each sample were measured. All groups were subjected to quasi-static loading at a 30-degree angle to the implant axis in a universal testing machine and 5 mm out of the implant support. RESULTS: After the implantoplasty, the mean final diameter was 3.13 +/- 0.033 mm for group 1, 3.23 +/- 0.023 mm for group 2, and 3.25 +/- 0.03 mm for group 3. The mean fracture strengths for the groups before and after the implantoplasty were, respectively, 773.1 +/- 13.16 N and 487.1 +/- 93.72 N in group 1; 829.4 +/- 14.12 N and 495.7 +/- 85.24 N in group 2; and 898.1 +/- 19.25 N and 717.6 +/- 77.25 N in group 3. CONCLUSION: Resistance to loading decreased significantly after implantoplasty, and varied among the three implant connection designs. PMID- 27183085 TI - Bactericidal Effect of Erbium-Doped Yttrium Aluminum Garnet Laser and Photodynamic Therapy on Aggregatibacter Actinomycetemcomitans Biofilm on Implant Surface. AB - PURPOSE: Peri-implantitis is a common complication of dental implants. The first step of treatment is elimination of bacterial biofilm and disinfection of the implant surface. This study sought to compare the effects of an erbium-doped yttrium aluminum garnet (Er:YAG) laser, photodynamic therapy using an indocyanin green-based photosensitizer (ICG-based PS) and diode laser, toluidine blue O (TBO) photosensitizer and light-emitting diode (LED) light source, and 2% chlorhexidine (CHX) on biofilm of Aggregatibacter actinomycetemcomitans to sandblasted, large-grit, acid-etched (SLA) implant surfaces. MATERIALS AND METHODS: Fifty SLA implants were divided into five groups and were incubated with A actinomycetemcomitans bacteria to form bacterial biofilm. Group 1 underwent Er:YAG laser radiation (with 10-Hz frequency, 100-mJ energy, and 1-W power); group 2 was subjected to LED (with 630-nm wavelength and maximum output intensity of 2.000 to 4.000 mW/cm(2)) and TBO as a photosensitizer; group 3 was exposed to diode laser radiation (with 810-nm wavelength and 300-mW power) and ICG-based PS; and group 4 was immersed in 2% CHX. Group 5 was the control group, and the samples were rinsed with normal saline. The number of colony-forming units (CFU) per implant was then calculated. Data were analyzed using one-way analysis of variance (ANOVA), and the five groups were compared. RESULTS: Significant differences was found between the control group and the other groups (P < .01). The lowest mean of CFU per implant count was in group 4 (P < .01), and the highest mean belonged to the control group. Photodynamic therapy by TBO + LED and ICG-based PS + diode laser was more effective than Er:YAG laser irradiation in suppression of this organism (P < .01). There was no significant difference between groups 2 and 3. CONCLUSION: The antibacterial effect of 2% CHX was greater than that of other understudy methods. PMID- 27183086 TI - Is Implant Flossing a Risk-Free Procedure? A Case Report with a 6-year Follow-up. AB - This study reports a case of peri-implantitis correlated with floss fibers trapped by the implant-prosthetic macrostructure. Discrepancy between the radiographic feature and probing depth was the starting point for a correct evaluation. The minimally invasive removal of the trapped material with the aid of a periodontal endoscope resulted in a complete resolution of the peri implantitis with a stable long-term result (6 years). This case report argues for some reconsiderations in hygienic, diagnostic, and therapeutic approaches in oral implantology. PMID- 27183087 TI - Impact of Crown-Implant Ratio of Single Restorations Supported by 6-mm Implants: A Short-Term Case Series Study. AB - PURPOSE: High crown-implant ratios might affect the biologic and technical performance of a reconstruction. The aim of this study was to assess whether a higher crown-implant ratio of single restorations on 6-mm implants resulted in more peri-implant bone loss and more prosthetic complications during a 1-year followup period. MATERIALS AND METHODS: A group of 37 patients were provided with 47 single-implant-supported restorations on 6-mm implants. Implants were placed in the posterior mandible or maxilla, where limited bone height was available. The clinical crown-implant ratio was determined on digitized casts. Peri-implant bone changes were analyzed on intraoral radiographs. Prosthetic complications were scored throughout the evaluation period. RESULTS: The mean crown-implant ratio was 2.14 +/- 0.42. The mean peri-implant bone loss was 0.13 +/- 0.36 mm. No complications occurred. CONCLUSION: High crown-implant ratios are not accompanied by increased peri-implant bone changes or prosthetic complications during a 1 year follow-up period. PMID- 27183088 TI - Implant Stability Development of Photofunctionalized Implants Placed in Regular and Complex Cases: A Case-Control Study. AB - PURPOSE: The objective of this study was to compare the rate of implant stability development of as-received and photofunctionalized dental implants in regular and complex cases. MATERIALS AND METHODS: Forty-nine implants (24 as-received and 25 photofunctionalized) placed in regular or complex cases (simultaneous guided bone regeneration, sinus elevation, or fresh extraction sockets) were studied. Photofunctionalization was performed by ultraviolet (UV) treatment of implants for 15 minutes using a photo device immediately prior to placement, and the generation of superhydrophilicity was confirmed. Implant stability was evaluated by measuring the implant stability quotient (ISQ) at placement (ISQ1) and at stage-two surgery (ISQ2). The rate of implant stability development was evaluated by calculating the osseointegration speed index (OSI), defined as the ISQ increase per month ([ISQ2-ISQ1]/healing time in months). The percentage of innate bone support at placement was evaluated clinically and radiographically. RESULTS: The average OSI was considerably greater for photofunctionalized implants (3.7 +/ 2.9) than for as-received implants (0.0 +/- 1.0). The OSI in complex cases was 4.2 +/- 3.2 for photofunctionalized implants and 0.2 +/- 0.9 for as-received implants. The OSI in cases with simultaneous sinus elevation was 5.5 +/- 3.5 for photofunctionalized implants and 0.2 +/- 1.1 for as-received implants. Photofunctionalized implants showed significantly higher ISQ2 values than as received implants. Photofunctionalized implant ISQ2 values were greater than 60, regardless of primary stability and innate bone support at placement. In multivariate analysis including the effects of photofunctionalization, age and sex of patients, and diameter and length of implants, photofunctionalization showed the strongest influence on the OSI for both regular and complex cases, while other factors influenced the OSI only in certain conditions. CONCLUSION: Photofunctionalization accelerated the rate and enhanced the final level of implant stability development compared with as-received implants, particularly for implants placed into poor-quality bone and other complex cases. Photofunctionalization was a stronger determinant of implant stability than all the other tested implant- and host-related factors. PMID- 27183089 TI - Utilizing a novel sorbent in the solid phase extraction for simultaneous determination of 15 pesticide residues in green tea by GC/MS. AB - Pesticide residues exceeding standard in green tea is a widespread problem of the world's attention, containing organochlorine pesticides (OCPs), organophosphorus pesticides (OPPs), and pyrethroids. In this research, three dimensionally honeycomb Mg-Al layered double oxide (TDH-Mg-Al-LDO) combined with graphitized carbon black (GCB), packed as a column, was used as a novel solid phase extraction sorbent, applying in simultaneous determination of 15 pesticide residues in green tea coupled with GC-MS. Compared with different type of SPE column, it showed that TDH-Mg-Al-LDO exhibited great advantages in the extraction of 15 pesticide residues from green tea, which was seldom reported before. Different experiment conditions, such as combination order of Mg-Al-LDO and GCB, dosage of sorbents, type and volume of eluting solvent were thoroughly studied and optimized. The limits of detection (LODs) of 15 pesticides ranged from 0.9 to 24.2ng/g and the limits of quantifications (LOQs) were ranging from 3.0 to 80.0ng/g. The recoveries using this method at three spiked concentration levels (10, 100 and 500ng/g for Fenthion, P,P'-DDE, O,P'-DDT, P,P'-DDD and Bifenthrin, 100, 500 and 2000ng/g for the others) range from 71.1 to 119.0%. The relative standard deviation (RSD) was from 0.1 to 7.6% in all case. The result indicated that the proposed analytical method had been successfully applied for the simultaneous determination of 15 pesticide residues in commercial green tea. PMID- 27183090 TI - Determination of unresolved heteronuclear scalar coupling constants by J(up) HSQMBC. AB - Long-range heteronuclear scalar coupling constants provide important structural information, which is necessary for obtaining stereospecific assignment or dihedral angle information. The measurement of small proton-carbon splittings is particularly difficult due to the low natural abundance of carbon-13 and the presence of homonuclear couplings of similar size. Here we present a real-time J upscaled HSQMBC, which allows the measurement of heteronuclear coupling constants even if they are hidden in the signal linewidth of a regular spectrum. PMID- 27183091 TI - RSV infection without ribavirin treatment in pediatric hematopoietic stem cell transplantation. PMID- 27183092 TI - Effect of severe hypoalbuminemia on toxicity of high-dose melphalan and autologous stem cell transplantation in patients with AL amyloidosis. AB - High-dose melphalan with stem cell transplantation (HDM/SCT) extends survival and induces hematologic and clinical responses in patients with light chain (AL) amyloidosis. Eighty percent of melphalan is bound to plasma proteins (60% albumin bound). We hypothesized that patients with profound hypoalbuminemia have a greater free melphalan fraction and more toxicity. Patients with AL amyloidosis treated with HDM/SCT between 2011 and 2014 with severe hypoalbuminemia (SH), defined as serum albumin ?2 g/dL were studied retrospectively. Sixteen patients with SH were identified. Forty-one patients without severe hypoalbuminemia (WSH) treated between 2011 and 2012 served as control. The incidence of acute renal failure requiring hemodialysis was 25% among patients with SH, compared with 5% among patients WSH (P=0.05). Not all patients who needed dialysis required it long term; 6.25% for SH and 2.44% for WSH (P=0.49). The rates of grade 3 or 4 febrile neutropenia and gastrointestinal toxicities were not significantly different between the groups. Engraftment kinetics were similar for both groups. Grade 4 renal toxicity and grade 3 lightheadedness were more frequent in patients with SH undergoing HDM/SCT for AL amyloidosis. Further studies into the mechanism of increased renal toxicity in patients with SH are warranted. PMID- 27183093 TI - A unique case of tuberculosis dissemination presenting as cutaneous lesions in a post allogeneic stem cell transplant patient. PMID- 27183094 TI - Melphalan 200 mg/m2 in patients with renal impairment is associated with increased short-term toxicity but improved response and longer treatment-free survival. AB - Data on the effectiveness and toxicity of high-dose melphalan in patients with renal impairment (RI) are lacking. We evaluated the impact of RI on outcomes of patients with multiple myeloma treated with melphalan 200 mg/m2 (Mel200) and autologous stem cell transplantation. Similar baseline characteristics were seen among 46 patients with creatinine clearance (CrCl) <60 mL/min (median 50 mL/min, range 20-59) and 103 patients with CrCl ?60 mL/min (median 83 mL/min, range 60 128). Patients with CrCl <60 mL/min had longer time to neutrophil (P=0.008) and platelet engraftment (P<0.001). Diarrhea, duration of total parenteral nutrition use and infection were significantly higher in the CrCl <60 mL/min group. With a median follow-up of 35 months (range 2-132) in the CrCl <60 mL/min group and 47 months (range 1-45) in the CrCl ?60 mL/min group, overall survival was comparable between the two groups. Median treatment-free survival was longer in the RI group (37 vs 17 months, P=0.0025). Multivariate analysis showed CrCl <60 mL/min (hazard ratio (HR) 3.5), and prior proteasome inhibitor therapy (HR 2.441) both predicted longer treatment-free survival. We consider Mel200 safe and effective in patients with CrCl between 30 and 60 mL/min. PMID- 27183095 TI - Brentuximab vedotin in combination with or without donor lymphocyte infusion for patients with Hodgkin lymphoma after allogeneic stem cell transplantation. AB - In our study, we evaluated the safety and efficacy of Brentuximab vedotin (BV) with or without the addition of donor lymphocyte infusion (DLI) after allogeneic stem cell transplantation (allo-SCT) in 16 patients with advanced Hodgkin lymphoma (HL). Thirteen patients with relapsed HL after allo-SCT received BV as treatment for active disease. Three patients without progression of HL after allo SCT received BV as consolidation. Twelve patients had been previously exposed to BV for treatment of relapse after autologous-SCT. Ten out of 16 patients received BV in combination with DLI. Among the 13 patients treated for active disease, CR and PR was observed in 7 and 2 patients, respectively. With a median follow-up of 13 months, 13 out of 16 patients are alive, while 3 died because of disease progression. The median PFS was 6 months. DLI-associated GVHD occurred in seven patients. Five patients with GVHD required immunosuppression, and in all cases, GVHD resolved after a short course of low dose steroids, implying that an anti GVHD modulating effect could be induced by the concurrent administration of BV. No serious adverse event was observed in any of the patients. PMID- 27183096 TI - Xenograft-directed personalized therapy for a patient with post-transplant relapse of ALL. PMID- 27183097 TI - Could renal impairment be a positive predictor of outcome in autografts for myeloma? PMID- 27183100 TI - Synthesis and Low Temperature Spectroscopic Observation of 1,3,5-Trioxane-2,4,6 Trione: The Cyclic Trimer of Carbon Dioxide. AB - 1,3,5-Trioxane-2,4,6-trione (cyclic trimer of CO2) is the product of a four-step synthesis: chlorination of isobutyraldehyde; cyclotrimerization of 2-chloro-2 methylpropanal; dehydochlorination of 2,4,6-tris(2-chloropropan)-2-yl-1,3,5 trioxane; ozonolysis at -80 degrees C of 2,4,6-tri(propan-2-ylidene)-1,3,5 trioxane. This trioxane-trione is detected in solution at temperatures between 80 to -40 degrees C, and its conversion to CO2 is monitored by (13)C NMR and FTIR. The CO2 trimer has a half-life of approximately 40 min at -40 degrees C. PMID- 27183099 TI - The Association of Chemotherapy-Induced Peripheral Neuropathy Symptoms and the Risk of Falling. AB - IMPORTANCE: Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of neurotoxic chemotherapy resulting in pain, sensory loss, and decreased quality of life. Few studies have prospectively examined the relationship between sensory neuropathy symptoms, falls, and fall-related injuries for patients receiving neurotoxic chemotherapy. OBJECTIVE: To determine the association between the symptoms of CIPN and the risk of falls for patients receiving neurotoxic chemotherapy. DESIGN, SETTING, AND PARTICIPANTS: In this secondary analysis of a prospective study, 116 patients with breast, ovarian, or lung cancer who were beginning neurotoxic chemotherapy with a taxane or platinum agent were recruited from oncology clinics. These patients would call a novel automated telephone system daily for 1 full course of chemotherapy. The telephone system (SymptomCare@Home) used a series of relevant CIPN questions to track symptoms on a 0 to 10 ordinal scale and contained a questionnaire about falls. Those reporting a numbness and tingling severity score of 3 or greater for at least 10 days were considered to have significant CIPN symptoms and were compared with those patients who did not. Data analysis was performed in November 2015. EXPOSURE: Chemotherapy with a neurotoxic taxane or platinum agent. MAIN OUTCOMES AND MEASURES: Patient-reported falls or near falls and fall-related injuries. The hypothesis was generated after data collection but prior to data analysis. RESULTS: Of the 116 patients who started neurotoxic chemotherapy (mean [SD] age was 55.5 [11.9] years, and 109 [94.0%] were female), 32 met the predetermined criteria for CIPN symptoms. The mean duration of follow-up was 62 days, with 51 telephone calls completed per participant. Seventy-four falls or near falls were reported. The participants with CIPN symptoms were nearly 3 times more likely to report a fall or near fall than the participants without CIPN symptoms (hazard ratio, 2.67 [95% CI, 1.62-4.41]; P < .001). The participants with CIPN symptoms were more likely than the participants without CIPN symptoms to obtain medical care for falls (8 of 32 participants with CIPN symptoms [25.0%] vs 6 of 84 participants without CIPN symptoms [7.1%]; P = .01). CONCLUSIONS AND RELEVANCE: These findings suggest that the sensory symptoms of CIPN are an indicator of an increased risk of falling and an increased use of health care resources. This study demonstrates the utility of a novel telephone-based system to track neuropathy symptoms. Careful monitoring and coaching of patients receiving neurotoxic chemotherapy for new sensory symptoms may facilitate more effective fall prevention strategies. PMID- 27183101 TI - Numerical simulation of compressible fluid flow in an ultrasonic suction pump. AB - Characteristics of an ultrasonic suction pump that uses a vibrating piston surface and a pipe are numerically simulated and compared with experimental results. Fluid analysis based on the finite-difference time-domain (FDTD) routine is performed, where the nonlinear term and the moving fluid-surface boundary condition are considered. As a result, the suction mechanism of the pump is found to be similar to that of a check valve, where the gap is open during the inflow phase, and it is nearly closed during the outflow phase. The effects of Reynolds number, vibration amplitude and gap thickness on the pump performance are analyzed. The calculated result is in good agreement with the previously measured results. PMID- 27183098 TI - Revised diagnosis and severity criteria for sinusoidal obstruction syndrome/veno occlusive disease in adult patients: a new classification from the European Society for Blood and Marrow Transplantation. AB - Sinusoidal obstruction syndrome, also known as veno-occlusive disease (SOS/VOD), is a potentially life threatening complication that can develop after hematopoietic cell transplantation. Although SOS/VOD progressively resolves within a few weeks in most patients, the most severe forms result in multi-organ dysfunction and are associated with a high mortality rate (>80%). Therefore, careful attention must be paid to allow an early detection of SOS/VOD, particularly as drugs have now proven to be effective and licensed for its treatment. Unfortunately, current criteria lack sensitivity and specificity, making early identification and severity assessment of SOS/VOD difficult. The aim of this work is to propose a new definition for diagnosis, and a severity-grading system for SOS/VOD in adult patients, on behalf of the European Society for Blood and Marrow Transplantation. PMID- 27183102 TI - Calcium Imaging of AM Dyes Following Prolonged Incubation in Acute Neuronal Tissue. AB - Calcium-imaging is a sensitive method for monitoring calcium dynamics during neuronal activity. As intracellular calcium concentration is correlated to physiological and pathophysiological activity of neurons, calcium imaging with fluorescent indicators is one of the most commonly used techniques in neuroscience today. Current methodologies for loading calcium dyes into the tissue require prolonged incubation time (45-150 min), in addition to dissection and recovery time after the slicing procedure. This prolonged incubation curtails experimental time, as tissue is typically maintained for 6-8 hours after slicing. Using a recently introduced recovery chamber that extends the viability of acute brain slices to more than 24 hours, we tested the effectiveness of calcium AM staining following long incubation periods post cell loading and its impact on the functional properties of calcium signals in acute brain slices and wholemount retinae. We show that calcium dyes remain within cells and are fully functional >24 hours after loading. Moreover, the calcium dynamics recorded >24 hrs were similar to the calcium signals recorded in fresh tissue that was incubated for <4 hrs. These results indicate that long exposure of calcium AM dyes to the intracellular cytoplasm did not alter the intracellular calcium concentration, the functional range of the dye or viability of the neurons. This data extends our previous work showing that a custom recovery chamber can extend the viability of neuronal tissue, and reliable data for both electrophysiology and imaging can be obtained >24hrs after dissection. These methods will not only extend experimental time for those using acute neuronal tissue, but also may reduce the number of animals required to complete experimental goals. PMID- 27183104 TI - Tracking dissociation dynamics of strong-field ionized 1,2-dibromoethane with femtosecond XUV transient absorption spectroscopy. AB - Using femtosecond time-resolved extreme ultraviolet absorption spectroscopy, the dissociation dynamics of the haloalkane 1,2-dibromoethane (DBE) have been explored following strong field ionization by femtosecond near infrared pulses at intensities between 7.5 * 10(13) and 2.2 * 10(14) W cm(-2). The major elimination products are bromine atoms in charge states of 0, +1, and +2. The charge state distribution is strongly dependent on the incident NIR intensity. While the yield of neutral fragments is essentially constant for all measurements, charged fragment yields grow rapidly with increasing NIR intensities with the most pronounced effect observed for Br(++). However, the appearance times of all bromine fragments are independent of the incident field strength; these are found to be 320 fs, 70 fs, and 30 fs for Br, Br(+), and Br(++), respectively. Transient molecular ion features assigned to DBE(+) and DBE(++) are observed, with dynamics linked to the production of Br(+) products. Neutral Br atoms are produced on a timescale consistent with dissociation of DBE(+) ions on a shallow potential energy surface. The appearance of Br(+) ions by dissociative ionization is also seen, as evidenced by the simultaneous decay of a DBE(+) ionic species. Dicationic Br(++) products emerge within the instrument response time, presumably from Coulomb explosion of triply charged DBE. PMID- 27183103 TI - Germinal center B cells recognize antigen through a specialized immune synapse architecture. AB - B cell activation is regulated by B cell antigen receptor (BCR) signaling and antigen internalization in immune synapses. Using large-scale imaging across B cell subsets, we found that, in contrast with naive and memory B cells, which gathered antigen toward the synapse center before internalization, germinal center (GC) B cells extracted antigen by a distinct pathway using small peripheral clusters. Both naive and GC B cell synapses required proximal BCR signaling, but GC cells signaled less through the protein kinase C-beta-NF-kappaB pathway and produced stronger tugging forces on the BCR, thereby more stringently regulating antigen binding. Consequently, GC B cells extracted antigen with better affinity discrimination than naive B cells, suggesting that specialized biomechanical patterns in B cell synapses regulate T cell-dependent selection of high-affinity B cells in GCs. PMID- 27183105 TI - Systemic oxidative DNA and RNA damage are not increased during early phases of psychosis: A case control study. AB - It has been suggested that patients with schizophrenia develop higher levels of oxidative stress, which may contribute to deteriorating mental illness. In order to examine oxidative stress in the early stages of severe mental illness, we examined the levels of systemic Deoxyribonucleic Acid (DNA) and Ribonucleic Acid (RNA) oxidation, 8-oxo-7,8-dihydro-2'-deoxyguanosine and 8-oxo-7,8 dihydroguanosine, perceived stress and recent life events in patients at ultra high-risk (UHR) of developing psychosis, in antipsychotic naive patients with first-episode schizophrenia (FES), and in healthy controls. We included 41 UHR patients, 35 FES patients, and 29 healthy controls. There was no difference in the level of DNA/RNA oxidative damage between UHR patients and FES patients compared with healthy controls. We found no association between levels of DNA/RNA oxidative damage and perceived stress/life events. Based on the results, we suggest that DNA and RNA oxidative markers are not increased during the early stages of illness, but further longitudinal studies in first-episode psychosis should be carried out to examine whether DNA and RNA oxidative damage are potential markers of severe illness. PMID- 27183106 TI - Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis. AB - A large array of studies have investigated peripheral oxytocin (OT) and vasopressin (ADH) as potential biomarkers of psychiatric disorders, with highly conflicting and heterogenous findings. We searched Web of KnowledgeSM and Scopus(r) for English original articles investigating OT and/or ADH levels in different biological fluids (plasma/serum, saliva, urine and cerebrospinal fluid) across several psychiatric disorders. Sixty-four studies were included. We conducted 19 preliminary meta-analyses addressing OT alterations in plasma/serum, saliva, urine and cerebrospinal fluid of 7 psychiatric disorders and ADH alterations in plasma/serum, saliva, urine and cerebrospinal fluid of 6 psychiatric disorders compared to controls. Hedge's g was used as effect size measure, together with heterogeneity analyses, test of publication biases and quality control. None of them (except serum OT in anorexia nervosa) revealed significant differences. There is no convincing evidence that peripheral ADH or OT might be reliable biomarkers in psychiatric disorders. However, the lack of significant results was associated with high methodological heterogeneity, low quality of the studies, small sample size, and scarce reliability of the methods used in previous studies, which need to be validated and standardized. PMID- 27183107 TI - Are nonclinical obsessive-compulsive symptoms associated with bias toward habits? AB - In a sample of student volunteers (N=93), we found that obsessive-compulsive symptoms (although not hoarding) were associated with overreliance on stimulus response habits at the expense of goal-directed control during instrumental responding. Only checking symptoms were associated with bias toward habits after negative affect was controlled for. Further research is warranted to examine if overreliance on habits represents an aberrant learning process that confers risk for obsessive-compulsive psychopathology. PMID- 27183108 TI - Borderline personality features in depressed or anxious patients. AB - Anxiety and depression frequently co-occur with borderline personality disorder. Relatively little research examined the presence of borderline personality features and its main domains (affective instability, identity problems, negative relationships and self-harm) in individuals with remitted and current anxiety and depression. Participants with current (n=597) or remitted (n=1115) anxiety and/or depression and healthy controls (n=431) were selected from the Netherlands Study of Depression and Anxiety. Assessments included the Personality Assessment Inventory - Borderline Features Scale and several clinical characteristics of anxiety and depression. Borderline personality features were more common in depression than in anxiety. Current comorbid anxiety and depression was associated with most borderline personality features. Anxiety and depression status explained 29.7% of the variance in borderline personality features and 3.8% (self-harm) to 31% (identity problems) of the variance in the four domains. A large part of the variance was shared between anxiety and depression but both disorders also explained a significant amount of unique variance. The severity of anxiety and depression and the level of daily dysfunctioning was positively associated with borderline personality features. Individuals with a longer duration of anxiety and depression showed more affective instability and identity problems. These findings suggest that patients with anxiety and depression may benefit from an assessment of personality pathology as it may have implications for psychological and pharmacological treatment. PMID- 27183109 TI - A possible effect of methylphenidate on state anxiety: A single dose, placebo controlled, crossover study in a control group. AB - Methylphenidate affects state-anxiety in ADHD patients. The current study examines the effect of Methylphenidate on state-anxiety in healthy subjects. In a cross-over, randomized, controlled, double-blind study, 36 healthy subjects received either Methylphenidate or placebo. As a group, no change in state anxiety was detected with Methylphenidate. However, participants reporting higher anxiety levels experienced a significant and specific state-anxiety reduction following Methylphenidate. Moreover, a strong negative correlation was found between the initial-level of anxiety and net-change in state-anxiety. These changes were unrelated to self-perceived attention levels. Our results point to the state-dependent effects of Methylphenidate on anxiety. PMID- 27183110 TI - Clinically relevant depression in old age: An international study with populations from Canada, Latin America and Eastern Europe. AB - Our aim is to assess cross-national variations in prevalence of clinically relevant depression and to examine the relationships of social and health factors with depression in five diverse populations of older adults, from Canada, Brazil, Colombia and Albania. We used the data from the International Mobility in Aging Study. Clinically relevant depression was defined as a score of >=16 on the Center for Epidemiologic Study Depression Scale (CES-D). Poisson regressions with robust covariance correction were used to estimate prevalence ratios associated with potential risk factors. Prevalence of clinically relevant depression across research sites varied widely, being consistently higher in women than in men. It was lowest in men from Brazil (6.3%) and highest in women from Albania (46.6%). Low education and insufficient income, living alone, multiple chronic conditions, and poor physical performance were all significantly associated with depression prevalence. Poor physical performance was more strongly associated with depression in men than in women. Similar factors are associated with clinically relevant depression among men and women and across research sites. The large variation in depression prevalence population rates is unexplained by the classical individual factors considered in the study suggesting the impact of country characteristics on depression among older populations. PMID- 27183111 TI - Incubation Temperature during Fetal Development Influences Morphophysiological Characteristics and Preferred Ambient Temperature of Chicken Hatchlings. AB - Skin and feather characteristics, which play a critical role in body temperature maintenance, can be affected by incubation circumstances, such as incubation temperature. However, no study to date has assessed the influence of incubation temperature during the fetal stage on morphometric characteristics and vascular development of the skin, feather characteristics, and their relationship to hormone levels and preferred temperature in later life in chickens. Broiler breeder eggs were exposed to low (36 degrees C), control (37.5 degrees C), or high (39 degrees C) temperatures (treatments LT, CK, and HT, respectively) from day 13 of incubation onward, because it is known that the endocrine axes are already established at this time. During this period, eggshell temperature of HT eggs (38.8+/-0.33 degrees C) was higher than of LT (37.4+/-0.08 degrees C) and CK eggs (37.8 +/-0.15 degrees C). The difference between eggshell and incubator air temperature diminished with the increasing incubation temperature, and was approximately zero for HT. HT hatchlings had higher surface temperature on the head, neck, and back, and thinner and more vascularized skin than did CK and LT hatchlings. No differences were found among treatments for body weight, total feather weight, number and length of barbs, barbule length, and plasma T4 concentration. LT hatchlings showed lower plasma T3 and GH, as well as lower T3/T4 ratio and decreased vascularity in the neck, back, and thigh skin compared to CK hatchlings. On the other hand, HT hatchlings had decreased skin thickness and increased vascularity, and preferred a higher ambient temperature compared to CK and HT hatchlings. In addition, for all treatments, surface temperature on the head was higher than of the other body regions. We conclude that changes in skin thickness and vascularity, as well as changes in thyroid and growth hormone levels, are the result of embryonic strategies to cope with higher or lower than normal incubation temperatures. Additionally exposure to increased temperature during incubation is an environmental factor that can exert early-life influence on ambient temperature preference of broiler hatchlings in later life. PMID- 27183112 TI - Laparoscopic Complete Mesocolic Excision for Stage II/III Left-Sided Colon Cancers: A Prospective Study and Comparison with D3 Lymph Node Dissection. AB - BACKGROUND: To investigate the similarities and differences of laparoscopic complete mesocolic excision (CME) to a colon resection with a D3 lymphadenectomy for the stage II/III left-sided colon carcinoma. METHODS: Patients between July 2011 and August 2014 were randomized into D3 and CME groups. Mesenteric area, log odds of positive lymph nodes (LODDS), and other operative parameters were collected and assessed. RESULTS: The average specimen sizes were 5730 +/- 828 mm(2) in superior rectal artery (SRA)-preserving D3, 8145 +/- 1022 mm(2) in SRA nonpreserving D3, and 8745 +/- 1039 mm(2) in the CME group; the differences were significant (P < .0001). The number of lymph nodes collected from CME specimens was larger, but the CME specimens did not contain an elevated value of LODDS or positive nodes or lymph node ratio (LNR). There were also no significant differences between recovery times of bowel function. Although it took more operation time in D3 approach, especially in SRA-preserving D3 operation, the difference was not significant. Concerning the leakage rate (P = .34) and vessel related complications (P = .64), there were no significant differences either. CONCLUSIONS: Both standard D3 resection and CME could achieve a high quality of mesocolic plane grade for stage II/III colon cancer. The LODDS and LNR were comparable, and those were not relevant to mesenteric size. PMID- 27183113 TI - The Expression of BTLA Was Increased and the Expression of HVEM and LIGHT Were Decreased in the T Cells of Patients with Rheumatoid Arthritis [corrected]. AB - BACKGROUND: Currently, the pathogenesis of rheumatoid arthritis (RA) is not clearly understood. The LIGHT/HVEM/BTLA co-signaling pathway may be involved in the pathogenesis of RA, although reports on the expression levels of LIGHT, HVEM and BTLA in T lymphocytes from RA patients are limited. METHOD: In this study, we recruited 30 healthy controls and 21 RA patients. Clinical characteristics were collected for RA patients. The levels of LIGHT, HVEM and BTLA expressed on the surface of circulating T cells of RA patients and healthy controls were measured by flow cytometry. RESULT: The percentages of CD3+, CD4+ and CD8+ T lymphocytes that expressed BTLA from RA patients were all higher than those of the controls (all p < 0.05), while the percentages of CD3+, CD4+ and CD8+ T lymphocytes that expressed HVEM and LIGHT were all lower than those of the controls (all p < 0.05). The rheumatoid factor and the percentage of HVEM+CD4+ T lymphocytes showed a statistically significant negative correlation in RA patients (r = -0.453, p = 0.039), as did the swollen joint count and the percentage of BTLA+CD8+ T lymphocytes (r = -0.501, p = 0.021). CONCLUSION: Here, we provide the first report on the increased expression of BTLA in T lymphocytes and on the decreased expression of HVEM and LIGHT in RA patients. BTLA, HVEM and LIGHT might be involved in the pathogenesis of RA and have the potential to be new clinically useful characteristics of RA. PMID- 27183114 TI - Protective effects of maternal methyl donor supplementation on adult offspring of high fat diet-fed dams. AB - Obesity has become a global public health problem associated with metabolic dysfunction and chronic disorders. It has been shown that the risk of obesity and the DNA methylation profiles of the offspring can be affected by maternal nutrition, such as high-fat diet (HFD) consumption. The aim of this study was to investigate whether metabolic dysregulation and physiological abnormalities in offspring caused by maternal HFD can be alleviated by the treatment of methyl donors during pregnancy and lactation of dams. Female C57BL/6 mice were assigned to specific groups and given different nutrients (control diet, Control+Met, HFD and HFD+Met) throughout gestation and lactation. Offspring of each group were weaned onto a control diet at 3 weeks of age. Physiological (weight gain and adipose composition) and metabolic (plasma biochemical analyses) outcomes were assessed in male and female adult offspring. Expression and DNA methylation profiles of obesogenic-related genes including PPAR gamma, fatty acid synthase, leptin and adiponectin were also detected in visceral fat of offspring. The results showed that dietary supplementation with methyl donors can prevent the adverse effects of maternal HFD on offspring. Changes in the expression and DNA methylation of obesogenic-related genes indicated that epigenetic regulation may contribute to the effects of maternal dietary factors on offspring outcomes. PMID- 27183115 TI - The information science of microbial ecology. AB - A revolution is unfolding in microbial ecology where petabytes of 'multi-omics' data are produced using next generation sequencing and mass spectrometry platforms. This cornucopia of biological information has enormous potential to reveal the hidden metabolic powers of microbial communities in natural and engineered ecosystems. However, to realize this potential, the development of new technologies and interpretative frameworks grounded in ecological design principles are needed to overcome computational and analytical bottlenecks. Here we explore the relationship between microbial ecology and information science in the era of cloud-based computation. We consider microorganisms as individual information processing units implementing a distributed metabolic algorithm and describe developments in ecoinformatics and ubiquitous computing with the potential to eliminate bottlenecks and empower knowledge creation and translation. PMID- 27183117 TI - Apoptosis of T-Cell Subsets after Acute High-Intensity Interval Exercise. AB - INTRODUCTION: High-intensity interval training (HIT) exercise has gained much interest in both performance and recreational sports. This study aims to compare the effect of HIT versus continuous (CONT) exercise with regard to changes of circulating T cells and progenitor cells. METHODS: Subjects (n = 23) completed an HIT test and an isocaloric CONT test. Blood samples were collected before, immediately after, and 3 and 24 h postexercise for the assessment of low differentiated (CD3CD28CD57), highly differentiated T cells (CD3CD28CD57), regulatory T cells (Tregs) (CD4CD25CD127), hematopoietic progenitor cells (CD45CD34), and endothelial progenitor cells (CD45CD34KDR) by flow cytometry. The detection of apoptosis was performed by using labeling with annexin V. To analyze potential mechanisms affecting T cells, several hormones and metabolites were analyzed. RESULTS: Both exercise tests induced an increase of catecholamines, cortisol, and thiobarbituric acid-reactive substances (P < 0.05). CONT induced a higher increase of apoptosis in low differentiated T cells compared with the HIT (CONT: 3.66% +/- 0.21% to 6.48% +/- 0.29%, P < 0.05; HIT: 3.43% +/- 0.31% to 4.71% +/- 0.33%), whereas HIT was followed by a higher rate of apoptotic highly differentiated T cells (CONT: 21.45% +/- 1.23% to 25.32% +/- 1.67%; HIT: 22.45% +/- 1.37% to 27.12% +/- 1.76%, P < 0.05). Regarding Tregs, HIT induced a mobilization, whereas CONT induced apoptosis in these cells (P < 0.05). The mobilization of progenitor cells did not differ between the exercise protocols. CONCLUSION: These results suggest that HIT deletes mainly highly differentiated T cells known to affect immunity to control latent infections. By contrast, CONT deletes mainly low differentiated T cells and Tregs, which might affect defense against new infectious agents. PMID- 27183116 TI - Potential Clinical Value of Multiparametric PET in the Prediction of Alzheimer's Disease Progression. AB - OBJECTIVE: To evaluate the potential clinical value of quantitative functional FDG PET and pathological amyloid-beta PET with cerebrospinal fluid (CSF) biomarkers and clinical assessments in the prediction of Alzheimer's disease (AD) progression. METHODS: We studied 82 subjects for up to 96 months (median = 84 months) in a longitudinal Alzheimer's Disease Neuroimaging Initiative (ADNI) project. All preprocessed PET images were spatially normalized to standard Montreal Neurologic Institute space. Regions of interest (ROI) were defined on MRI template, and standard uptake values ratios (SUVRs) to the cerebellum for FDG and amyloid-beta PET were calculated. Predictive values of single and multiparametric PET biomarkers with and without clinical assessments and CSF biomarkers for AD progression were evaluated using receiver operating characteristic (ROC) analysis and logistic regression model. RESULTS: The posterior precuneus and cingulate SUVRs were identified for both FDG and amyloid beta PET in predicating progression in normal controls (NCs) and subjects with mild cognitive impairment (MCI). FDG parietal and lateral temporal SUVRs were suggested for monitoring NCs and MCI group progression, respectively. 18F-AV45 global cortex attained (78.6%, 74.5%, 75.4%) (sensitivity, specificity, accuracy) in predicting NC progression, which is comparable to the 11C-PiB global cortex SUVR's in predicting MCI to AD. A logistic regression model to combine FDG parietal and posterior precuneus SUVR and Alzheimer's Disease Assessment Scale Cognitive (ADAS-Cog) Total Mod was identified in predicating NC progression with (80.0%, 94.9%, 93.9%) (sensitivity, specificity, accuracy). The selected model including FDG posterior cingulate SUVR, ADAS-Cog Total Mod, and Mini-Mental State Exam (MMSE) scores for predicating MCI to AD attained (96.4%, 81.2%, 83.6%) (sensitivity, specificity, accuracy). 11C-PiB medial temporal SUVR with MMSE significantly increased 11C-PiB PET AUC to 0.915 (p<0.05) in predicating MCI to AD with (77.8%, 90.4%, 88.5%) (sensitivity, specificity, accuracy). CONCLUSION: Quantitative FDG and 11C-PiB PET with clinical cognitive assessments significantly improved accuracy in the predication of AD progression. PMID- 27183118 TI - Raw Accelerometer Data Analysis with GGIR R-package: Does Accelerometer Brand Matter? AB - PURPOSE: This study aimed to determine the agreement between outputs from contemporaneous measures of acceleration from wrist-worn GENEActiv and ActiGraph accelerometers when processed using the GGIR open source package. METHODS: Thirty four participants wore a GENEActiv and an ActiGraph GT3X+ on their nondominant wrist continuously for 2 d to ensure the capture of one 24-h day and one nocturnal sleep. GENEActiv.bin files and ActiGraph .csv files were analyzed with R-package GGIR version 1.2-0. Key outcome variables were as follows: wear time, average magnitude of dynamic wrist acceleration (Euclidean norm minus one [ENMO]), percentile distribution of accelerations, time spent across acceleration levels in a 40-mg resolution, time in moderate-to-vigorous physical activity (MVPA: total, 10-min bouts), and duration of nocturnal sleep. RESULTS: There was a high agreement between accelerometer brands for all derived outcomes (wear time, MVPA, and sleep; intraclass correlation coefficient [ICC] > 0.96), ENMO (ICC = 0.99), time spent across acceleration levels (ICC > 0.93), and accelerations >=50th percentile of the distribution (ICC > 0.82). ENMO (mean +/- SD, GENEActiv = 29.9 +/- 20.7 mg, ActiGraph = 27.8 +/- 21.4 mg) and accelerations between the 5th and the 75th percentile of the distribution measured by the GENEActiv were significantly higher than those measured by the ActiGraph. Correspondingly, the number of minutes recorded between 0 and 40 mg was significantly greater for the ActiGraph (745 min cf. 734 min), and the number of minutes recorded between 40 and 80 mg was significantly greater for the GENEActiv (110 min cf. 105 min). CONCLUSION: Derived outcomes (wear time, MVPA, and sleep) were similar between brands. Brands compared well for acceleration magnitudes >50 80 mg but not lower magnitudes indicative of sedentary time. Caution is advised when comparing the magnitude of ENMO between brands, but there was a high consistency between brands for the ranking of individuals for activity and sleep outcomes. PMID- 27183119 TI - Advances in Exercise, Fitness, and Performance Genomics in 2015. AB - This review of the exercise genomics literature encompasses the highest-quality articles published in 2015 across seven broad topics: physical activity behavior, muscular strength and power, cardiorespiratory fitness and endurance performance, body weight and adiposity, insulin and glucose metabolism, lipid and lipoprotein metabolism, and hemodynamic traits. One study used a quantitative trait locus for wheel running in mice to identify single nucleotide polymorphisms (SNPs) in humans associated with physical activity levels. Two studies examined the association of candidate gene ACTN3 R577X genotype on muscular performance. Several studies examined gene-physical activity interactions on cardiometabolic traits. One study showed that physical inactivity exacerbated the body mass index (BMI)-increasing effect of an FTO SNP but only in individuals of European ancestry, whereas another showed that high-density lipoprotein cholesterol (HDL C) SNPs from genome-wide association studies exerted a smaller effect in active individuals. Increased levels of moderate-to-vigorous-intensity physical activity were associated with higher Matsuda insulin sensitivity index in PPARG Ala12 carriers but not Pro12 homozygotes. One study combined genome-wide and transcriptome-wide profiling to identify genes and SNPs associated with the response of triglycerides (TG) to exercise training. The genome-wide association study results showed that four SNPs accounted for all of the heritability of ?TG, whereas the baseline expression of 11 genes predicted 27% of ?TG. A composite SNP score based on the top eight SNPs derived from the genomic and transcriptomic analyses was the strongest predictor of DeltaTG, explaining 14% of the variance. The review concludes with a discussion of a conceptual framework defining some of the critical conditions for exercise genomics studies and highlights the importance of the recently launched National Institutes of Health Common Fund program titled "Molecular Transducers of Physical Activity in Humans." PMID- 27183120 TI - Effects of Footwear and Fatigue on Running Economy and Biomechanics in Trail Runners. AB - PURPOSE: This study aimed to examine the effects of footwear and neuromuscular fatigue induced by short distance trail running (TR) on running economy (RE) and biomechanics in well-trained and traditionally shod runners. METHODS: RE, vertical and leg stiffness (Kvert and Kleg), as well as foot strike angle were measured from two 5-min treadmill running stages performed at a speed of 2.5 (with 10% grade, uphill running) and 2.77 m.s (level running) before and after an 18.4-km TR exercise (approximately 90% of maximal heart rate) in runners wearing minimalist shoes (MS), MS plus added mass (MSm), or traditional shoes (TS). Maximal voluntary contraction torque of knee extensors and perceived muscle pain were also evaluated before and after TR. RESULTS: Maximal voluntary contraction values decreased after TR in all footwear conditions (P < 0.001), indicating the occurrence of neuromuscular fatigue. In the nonfatigued condition, runners exhibited a better RE only during level running in MS and MSm (i.e., combined effects of shoe mass and midsole geometry), in association with significant decreases in foot strike angle (P < 0.05). However, no significant difference in RE was observed between shod conditions after TR during either uphill or level running. Decreases in both Kvert/Kleg and foot strike angle were more pronounced during running in MS and MSm (P < 0.05) compared with TS, whatever the period. Calf pain increased after TR when wearing MS and MSm compared with TS (P < 0.05). CONCLUSIONS: These findings indicated specific alterations in RE and biomechanics over time during the MS and MSm conditions compared with the TS condition. Future studies are warranted to evaluate the relationship between RE and footwear with fatigue in experienced minimally shod runners. PMID- 27183121 TI - Cardiorespiratory Fitness Is Associated with Better Executive Function in Young Women. AB - PURPOSE: A positive association between cardiorespiratory fitness (CRF) and cognitive function has been demonstrated mainly in children and older adults. Women attending college live in a cognitively demanding setting where optimal cognition matters but often experience declines in CRF. Our aim was to test whether CRF is associated with executive function in young adult women. METHODS: Participants in this cross-sectional study included 120 healthy women age 18-35 yr in a university setting. Each woman completed a maximal treadmill-based exercise test to determine peak oxygen uptake (VO2peak), computerized tests of executive function, and questionnaires to assess motivation and other factors with potential to influence physical and cognitive performance. RESULTS: Overall CRF was excellent, with a sample mean VO2peak of 44.6 mL.min.kg. After adjusting for covariates, higher VO2peak was associated with better performance on attention (P < 0.01), learning/shifting (P < 0.01), working memory (P < 0.01), and problem-solving (P < 0.05) tasks. Likewise, when women were grouped according to the American College of Sports Medicine fitness classification, performance on executive function tasks was poorest in women with very poor or poor CRF. Women with superior CRF performed best on executive function tasks, and performance was intermediate in women with fair, good, or excellent CRF. CONCLUSION: The findings from this cross-sectional study suggest that optimal cognition is related to CRF in young adult women. Future studies are needed to test whether strategies to improve CRF are effective in improving cognitive function. PMID- 27183123 TI - Accuracy of Wristband Activity Monitors during Ambulation and Activities. AB - PURPOSE: The main purpose of this study was to examine the accuracy of wristband activity monitors on measuring step counts at prescribed speeds on a treadmill and under short bouts of common daily activities. METHODS: Thirty healthy young adults wore three wristband activity monitors on both wrists while walking or jogging on a treadmill at different speeds (54, 80, 107, and 134 m.min) and performing six different common daily activities for 5 min each. The monitors included the Fitbit Flex, the Garmin Vivofit, and the Jawbone UP. The common daily activity conditions included two sitting activities (playing a tablet computer game and folding laundry), two walking activities (pushing a stroller, carrying a bag), and two stair climbing activities (down and up). Absolute percentage error (APE) scores were computed to examine the accuracy between actual observed steps and monitor-detected steps. RESULTS: Under the treadmill condition, the APE ranged between 1.5% and 9.6%. Accuracy was improved at faster speeds (134 m.min) for all the monitors (APE < 2.5%). In the common daily activity conditions, substantial step counts were registered when folding laundry. All monitors significantly underestimated actual steps (all APE >33%) when pushing a stroller. Higher APE was observed when worn on the dominant wrist under the common daily activity conditions. CONCLUSIONS: The wristband activity monitors examined were more accurate for measuring step counts between 80 and 134 m.min as compared with a slower speed. Accuracy under each common daily activity condition ranged widely between monitors and activity, with less error when worn on the nondominant wrist. These results will help to inform researchers on the use and accuracy of wristband activity monitors for future studies. PMID- 27183122 TI - New Insights into Activity Patterns in Children, Found Using Functional Data Analyses. AB - INTRODUCTION/PURPOSE: Continuous monitoring of activity using accelerometers and other wearable devices provides objective, unbiased measurement of physical activity in minute-by-minute or finer resolutions. Accelerometers have already been widely deployed in studies of healthy aging, recovery of function after heart surgery, and other outcomes. Although common analyses of accelerometer data focus on single summary variables, such as the total or average activity count, there is growing interest in the determinants of diurnal profiles of activity. METHODS: We use tools from functional data analysis (FDA), an area with an established statistical literature, to treat complete 24-h diurnal profiles as outcomes in a regression model. We illustrate the use of such models by analyzing data collected in New York City from 420 children participating in a Head Start program. Covariates of interest include season, sex, body mass index z-score, presence of an asthma diagnosis, and mother's birthplace. RESULTS: The FDA model finds several meaningful associations between several covariates and diurnal profiles of activity. In some cases, including shifted activity patterns for children of foreign-born mothers and time-specific effects of asthma on activity, these associations exist for covariates that are not associated with average activity count. CONCLUSION: FDA provides a useful statistical framework for settings in which the effect of covariates on the timing of activity is of interest. The use of similar models in other applications should be considered, and we make code public to facilitate this process. PMID- 27183125 TI - Comparative Physiology of Fatigue. AB - This review attempts to provide insights into factors associated with fatigue in human and nonhuman animals by using the two fundamental approaches of comparative physiology: determining common principles that govern structure and function in animals that are relatively invariant between animals and evaluating animals that have been highly adapted by natural selection to demonstrate extreme performance. In this review, I approach the topic of fatigue by considering factors that are associated with its reciprocal or inverse or duration of sustained performance before fatigue sets in to end the performance. The two general factors that I consider that affect endurance time more than any other are body temperature and body mass. The former affects endurance time because of thermodynamic effects on chemical reaction rates and metabolism; the latter acts through the mechanism of allometry or scaling. The examples of extreme animal performance that I discuss are two examples of bird migration, the diving performance of marine mammals, and the unique relationship that governs energy cost of locomotion in hopping kangaroos. PMID- 27183124 TI - Fatigue Exacerbation by Interval or Continuous Exercise in Chronic Fatigue Syndrome. AB - PURPOSE: The objective of this study is to determine whether the typical exacerbation of symptoms in patients with chronic fatigue syndrome (CFS) after a bout of exercise differs between high-intensity interval training (HIIT) or continuous (CONT) aerobic exercise of the same duration and mechanical work. METHODS: Participants with specialist-diagnosed CFS performed two 20-min bouts of cycling in a randomized crossover study. The bouts were either moderate-intensity continuous (70% age-predicted HR maximum) or high-intensity interval exercise, separated by at least 2 wk. Self-report questionnaires capturing fatigue, the related symptoms, and actigraphy were collected across 2 d before and 4 d after the exercise. Comparisons between exercise bouts were made using paired sample t tests. RESULTS: Fourteen moderately affected participants who were unable to work, but not bed bound, completed the study (nine female, 32 +/- 10 yr, 67 +/- 11 kg). Mechanical work was matched successfully between the exercise bouts (HIIT, 83,037, vs CONT, 83,348 J, P = 0.84). Mean HR (HIIT, 76% +/- 5%, vs CONT, 73% +/- 6% age-predicted HR maximum, P < 0.05) and RPE (6-20) in the legs (HIIT, 15.4 +/- 1.4, vs CONT, 13.2 +/- 1.2, P < 0.001) were higher for the interval compared with continuous exercise. Mean fatigue scores (0-10) were similar before each exercise challenge (HIIT, 4.5 +/- 1.8, vs CONT, 4.1 +/- 1.7, P = 0.43). Participants reported an increase in fatigue scores after both challenges (mean difference: HIIT, 1.0 +/- 1.3, P < 0.01; CONT, 1.5 +/- 0.7, P < 0.001), but these exacerbations in fatigue were not statistically or clinically different (P = 0.20). CONCLUSIONS: High-intensity interval exercise did not exacerbate fatigue any more than continuous exercise of comparable workload. This finding supports evaluation of HIIT in graded exercise therapy interventions for patients with CFS. PMID- 27183126 TI - Interaction of Toll-Like Receptors with the Molecular Chaperone Gp96 Is Essential for Its Activation of Cytotoxic T Lymphocyte Response. AB - The heat shock protein gp96 elicits specific T cell responses to its chaperoned peptides against cancer and infectious diseases in both rodent models and clinical trials. Although gp96-induced innate immunity, via a subset of Toll like receptors (TLRs), and adaptive immunity, through antigen presentation, are both believed to be important for priming potent T cell responses, direct evidence for the role of gp96-mediated TLR activation related to its functional T cell activation is lacking. Here, we report that gp96 containing mutations in its TLR binding domain failed to activate macrophages, but peptide presentation was unaffected. Moreover, we found that peptide-specific T cell responses, as well as antitumor T cell immunity induced by gp96, are severely impaired when the TLR binding domain is mutated. These data demonstrate the essential role of the gp96 TLR interaction in priming T cell immunity and provide further molecular basis for the coupling of gp96-mediated innate with adaptive immunity. PMID- 27183128 TI - Correction: IL-6 Expression Regulates Tumorigenicity and Correlates with Prognosis in Bladder Cancer. AB - [This corrects the article DOI: 10.1371/journal.pone.0061901.]. PMID- 27183127 TI - Differences of Intra-Articular Graft Length between Sandwich-Style Reconstruction and Zhao-Style Non-Remnant-Preserving Double-Bundle Reconstruction of Posterior Cruciate Ligament. AB - Appropriate graft length within the joint and inside the osseous tunnel is essential for achieving posterior stability and adequate anchorage strength. Because of the curving path and thickness of the graft in double-bundle posterior cruciate ligament (PCL) reconstruction, especially in double-bundle PCL augmentation (with remnant preservation), the actual intra-articular length of PCL grafts, which remains unknown, may be longer than previously published values. The main purpose of the current study is to measure the actual intra articular graft length required in sandwich-style PCL reconstruction (remnant preserving double-bundle PCL augmentation) and Zhao-style non-remnant-preserving double-bundle PCL reconstruction (semi-anatomic double-bundle PCL reconstruction using double-double tunnel with tibial medial and lateral arrangement). Nine matched pairs of intact cadaveric knees were randomized between two groups and respectively received sandwich-style PCL reconstruction (remnant-preserving group) and Zhao-style non-remnant-preserving double-bundle PCL reconstruction (non-remnant-preserving group). The tunnel positions were exactly the same in two groups. The anterolateral (AL) bundle was reconstructed with four-stranded semitendinosus tendon, and the posteromedial (PM) bundle was reconstructed with four-stranded gracilis tendon. For each bundle, the length of the graft portion within the joint was measured. The current study indicated that in remnant preserving group, the average intra-articular exposed portion was 42.0 mm (SD, 1.3 mm; range, 40.0 mm to 43.4 mm) for the AL bundle and 32.5 mm (SD, 2.9 mm; range, 27.8 mm to 35.8 mm) for the PM bundle. In non-remnant-preserving group, the intra-articular exposed portion was 34.5 mm (SD, 1.0 mm; range, 32.7 mm to 36.0 mm) for the AL bundle and 29.1 mm (SD, 2.1 mm; range, 25.2 mm to 31.9 mm) for the PM bundle. For both the AL and PM bundles, significant differences were found in average intra-articular graft length between the two groups. The current study, whose methodology is more rigorous and accurate by measuring the actual intra-articular graft length, has direct applications to clinical practice. When considering the total graft lengths during reconstruction, it is necessary to recognize that remnant PCL has a space occupation effect on graft and that remnant preservation requires longer intra-articular graft lengths than non remnant preservation. PMID- 27183129 TI - Interaction of Atmospheric-Pressure Air Microplasmas with Amino Acids as Fundamental Processes in Aqueous Solution. AB - Plasma medicine is a relatively new field that investigates potential applications of cold atmospheric-pressure plasmas in bioengineering, such as for bacterial inactivation and degradation of organic molecules in water. In order to enunciate mechanisms of bacterial inactivation at molecular or atomic levels, we investigated the interaction of atmospheric-pressure air microplasmas with amino acids in aqueous solution by using high-resolution mass spectrometry (HRMS). Results show that the oxidation effect of plasma-induced species on the side chains of the amino acids can be categorized into four types, namely hydroxylation, nitration, dehydrogenation and dimerization. In addition, relative activities of amino acids resulting from plasma treatment come in descending order as follows: sulfur-containing carbon-chain amino acids > aromatic amino acids > five-membered ring amino acids > basic carbon-chain amino acids. Since amino acids are building blocks of proteins vital to the growth and reproduction of bacteria, these results provide an insight into the mechanism of bacterial inactivation by plasma. PMID- 27183130 TI - Waiting time prioritisation: Evidence from England. AB - A number of OECD countries have introduced waiting time prioritisation policies which give explicit priority to severely ill patients with high marginal disutility of waiting. There is however little empirical evidence on how patients are actually prioritised. We exploit a unique opportunity to investigate this issue using a large national dataset with accurate measures of severity on nearly 400,000 patients. We link data from a national patient-reported outcome measures survey to administrative data on all patients waiting for a publicly funded hip and knee replacement in England during the years 2009-14. We find that patients suffering the most severe pain and immobility have shorter waits than those suffering the least, by about 24% for hip replacement and 11% for knee replacement, and that the association is approximately linear. These differentials are more closely associated with pain than immobility, and are larger in hospitals with longer average waiting times. These result suggests that doctors prioritise patients according to severity even when no formal prioritisation policy is in place and average waiting times are short. PMID- 27183131 TI - Is Development Assistance for Health fungible? Findings from a mixed methods case study in Tanzania. AB - The amount of Development Assistance for Health (DAH) available to low- and middle-income countries has increased exponentially over the past decade. However, there are concerns that DAH increases have not resulted in increased spending on health at the country level. This is because DAH may be fungible, resulting from the recipient government decreasing its contribution to the health sector as a result of external funding. The aim of this research is to assess whether DAH funds in Tanzania are fungible, by exploring government substitution of its own resources across sectors and within the health sector. A database containing 28140 projects of DAH expenditure between 2000 and 2010 was compiled from the Organisation for Economic Co-operation and Development's Creditor Reporting System (OECD-CRS) and AidData databases. Government health expenditure data for the same period were obtained from the Government of Tanzania, World Bank, public expenditure reviews and budget speeches and analysed to assess the degree of government substitution. 22 semi-structured interviews were conducted with Development Partners (DPs), government and non-government stakeholders between April and June 2012 to explore stakeholder perceptions of fungibility. We found some evidence of substitution of government funds at the health sector and sub-sector levels and two mechanisms through which it takes place: the resource allocation process and macro-economic factors. We found fungibility of external funds may not necessarily be detrimental to Tanzania's development (as evidence suggests the funds displaced may be reallocated to education) and the mechanisms used by DPs to prevent substitution were largely ineffective. We recommend DPs engage more effectively in the priority-setting process, not just with the Ministry of Health and Social Welfare (MoHSW), but also with the Ministry of Finance, to agree on priorities and mutual funding responsibilities at a macroeconomic level. We also call for more qualitative research on fungibility. PMID- 27183132 TI - How do individuals' health behaviours respond to an increase in the supply of health care? Evidence from a natural experiment. AB - The efficacy of the management of long-term conditions depends in part on whether healthcare and health behaviours are complements or substitutes in the health production function. On the one hand, individuals might believe that improved health care can raise the marginal productivity of their own health behaviour and decide to complement health care with additional effort in healthier behaviours. On the other hand, health care can lower the cost of unhealthy behaviours by compensating for their negative effects. Individuals may therefore reduce their effort in healthier lifestyles. Identifying which of these effects prevails is complicated by the endogenous nature of treatment decisions and individuals' behavioural responses. We explore whether the introduction in 2004 of the Quality and Outcomes Framework (QOF), a financial incentive for family doctors to improve the quality of healthcare, affected the population's weight, smoking and drinking behaviours by applying a sharp regression discontinuity design to a sample of 32,102 individuals in the Health Survey for England (1997-2009). We find that individuals with the targeted health conditions improved their lifestyle behaviours. This complementarity was only statistically significant for smoking, which reduced by 0.7 cigarettes per person per day, equal to 18% of the mean. We investigate whether this change was attributable to the QOF by testing for other discontinuity points, including the introduction of a smoking ban in 2007 and changes to the QOF in 2006. We also examine whether medication and smoking cessation advice are potential mechanisms and find no statistically significant discontinuities for these aspects of health care supply. Our results suggest that a general improvement in healthcare generated by provider incentives can have positive unplanned effects on patients' behaviours. PMID- 27183133 TI - Increased incidence but improved median overall survival for biliary tract cancers diagnosed in Ontario from 1994 through 2012: A population-based study. AB - BACKGROUND: To the authors' knowledge, the incidence of biliary tract cancer (BTC) in Canada is unknown. In the current study, the authors sought to describe the epidemiology of BTC using a large population-based cancer database from Ontario, Canada. METHODS: The current study was a population-based cohort study using the Ontario Cancer Registry. Patients with intrahepatic cholangiocarcinoma (IHCC), extrahepatic cholangiocarcinoma (EHCC), and gallbladder cancer (GBC) diagnosed between 1994 and 2012 were included. Age-standardized incidence and mortality rates were compared using incidence rate ratios (IRRs). Overall survival from the time of diagnosis was calculated for 3 eras: 1994 through 1999, 2000 through 2005, and 2006 through 2012. The number of patients receiving chemotherapy, radiotherapy, or surgery was determined using linked clinical data. RESULTS: A total of 9039 cases (1569 IHCC cases, 4337 EHCC cases, and 3133 GBC cases) were identified. The rate of BTC increased by 1.6% per year (IRR, 1.016; 95% confidence interval [95% CI], 1.008-1.024 [P<.001]). The incidence increased by 7.0% per year among cases of IHCC (IRR, 1.070; 95% CI, 1.058-1.081 [P<.001]) and 1.8% per year in cases of EHCC (IRR, 1.018; 95% CI, 1.009-1.027 [P<.001]), whereas the incidence of GBC remained unchanged (IRR, 0.991; 95% CI, 0.982-1.001 [P = .086]). The median survival for the cohort was 8.3 months, with improvement noted over the study period (6.1 months for 1994-1999 vs 8.5 months for 2000-2005 vs 10.3 months for 2006-2012 [P<.001]). The median survival was the longest for EHCC (11.3 months), followed by GBC (6.4 months) and IHCC (6.2 months). The percentage of patients receiving chemotherapy and/or radiotherapy increased over the study (P<.001), whereas the percentage of patients receiving surgery decreased (P<.001). CONCLUSIONS: An increased incidence of BTC during 1994 through 2012 was observed. Explanations for the observed temporal improvement in median survival require further exploration. Cancer 2016;122:2534-43. (c) 2016 American Cancer Society. PMID- 27183134 TI - What Unites Palliative Care on Both Sides of the Atlantic? Experiences of a Third Year Medical Student. PMID- 27183135 TI - Concerted Uranium Research in Europe (CURE): toward a collaborative project integrating dosimetry, epidemiology and radiobiology to study the effects of occupational uranium exposure. AB - The potential health impacts of chronic exposures to uranium, as they occur in occupational settings, are not well characterized. Most epidemiological studies have been limited by small sample sizes, and a lack of harmonization of methods used to quantify radiation doses resulting from uranium exposure. Experimental studies have shown that uranium has biological effects, but their implications for human health are not clear. New studies that would combine the strengths of large, well-designed epidemiological datasets with those of state-of-the-art biological methods would help improve the characterization of the biological and health effects of occupational uranium exposure. The aim of the European Commission concerted action CURE (Concerted Uranium Research in Europe) was to develop protocols for such a future collaborative research project, in which dosimetry, epidemiology and biology would be integrated to better characterize the effects of occupational uranium exposure. These protocols were developed from existing European cohorts of workers exposed to uranium together with expertise in epidemiology, biology and dosimetry of CURE partner institutions. The preparatory work of CURE should allow a large scale collaborative project to be launched, in order to better characterize the effects of uranium exposure and more generally of alpha particles and low doses of ionizing radiation. PMID- 27183136 TI - Inter- and intraobserver agreement of ADC measurements of lung cancer in free breathing, breath-hold and respiratory triggered diffusion-weighted MRI. AB - OBJECTIVE: To prospectively evaluate the inter- and intraobserver agreement of apparent diffusion coefficient (ADC) measurements in free breathing, breath-hold, and respiratory triggered diffusion-weighted imaging (DWI) of lung cancer. METHODS: Twenty-two patients with lung cancer (tumor size >2cm) underwent DWIs (3.0T) in three imaging methods. Lesion ADCs were measured twice by both of the two independent observers and compared. RESULTS: No statistical significance was found among methods, though respiratory-triggered DWI tended to have higher ADCs than breath-hold DWI. Great inter- and intraobserver agreement was shown. CONCLUSION: ADCs had good inter- and intraobserver agreement in all three DWI methods. PMID- 27183137 TI - Synchronous pancreatic adenocarcinoma and intrahepatic cholangiocarcinoma arising in the context of intraductal papillary neoplasms. AB - Field cancerization theory provides rationale for the development of multiple pancreatic ductal and biliary lesions in a single patient through the development and accumulation of multiple genetic changes. Genetic alterations result in the development of precursor lesions including intraductal papillary mucinous neoplasms of the pancreas (IPMN), intraductal papillary neoplasm of the bile duct (IPN-B), and their malignant counterparts, pancreatic adenocarcinoma and cholangiocarcinoma. Although IPMN are frequently encountered, IPN-B are uncommon and the synchronous occurrence of both lesions is rare. We present a case of synchronous pancreatic adenocarcinoma and intrahepatic cholangiocarcinoma with histopathologic evidence of underlying precursor lesions, IPMN-P and IPN-B. PMID- 27183138 TI - Contrast-induced nephropathy in outpatients with preexisting renal impairment: a comparison between intravenous iohexol and iodixanol. AB - BACKGROUND: Concern for contrast-induced nephropathy (CIN) may result in administration of more costly agents. We prospectively compared outpatient CIN incidence of iodixanol to iohexol. METHODS: Patients were randomized to receive 100ml of iohexol (n=47) or iodixanol (n=55). We compared patients who developed CIN using the Wilson score interval and also calculated an odds ratio for the development of CIN. RESULTS: CIN rate for iohexol was 2% compared to 9% for iodixanol. Those receiving iodixanol were almost 5 times more likely to experience CIN. CONCLUSION: These results do not suggest a benefit of iodixanol over iohexol in the study population. PMID- 27183139 TI - Biplane versus short-axis measures of the left atrium and ventricle in patients with systolic dysfunction assessed by magnetic resonance. AB - PURPOSE: This study aims to investigate if the time saving biplane method can be an alternative to short-axis measurements for left atrium (LA) and left ventricle (LV) in cardiac magnetic resonance of patients with extensive LV remodeling. MATERIALS AND METHODS: In 45 patients with coronary artery disease and systolic LV dysfunction [ejection fraction (EF)<50%], LA and LV end-diastolic volume, end systolic volume, stroke volume, and EF were measured by the biplane area length and by the short-axis volume method. RESULTS: No statistical differences between the biplane area length and short-axis volume were found for the LA end-systolic or the LV end-diastolic volumes. However, the biplane area length method overestimated LA stroke volume by 7.1+/-12.3 ml, LA EF by 6.7+/-8.8% (both P<.001), LV stroke volume by 6.2+/-12.9 ml (P=.002), and LV EF by 2.6+/-4.6% (P<.001). The differences in LV measurements were more evident in patients with severely distorted LV. For LA volume parameters, overall consistency between biplane area length and short-axis approach was good [all intraclass correlation coefficient (ICC)>=0.74] and for LV volume parameters, overall consistency between both approaches was excellent (all ICC>=0.93). CONCLUSION: In patients with LV systolic dysfunction, the short-axis volume is superior to the biplane method and should be the first choice, when accurate determination of LA and LV EF is the main clinical indication for cardiac magnetic resonance. PMID- 27183140 TI - The diagnostic value of combination of TI-RADS and ultrasound elastography in the differentiation of benign and malignant thyroid nodules. AB - BACKGROUND: Here, we evaluated the diagnostic value of combination of thyroid imaging-reporting and data system (TI-RADS) and ultrasound elastography (USE) in risk assessment of thyroid nodules. METHODS: The clinical data of 174 patients with 232 nodules were retrospectively analyzed. All nodules were examined by gray scale ultrasonography and USE and confirmed by histological examination. RESULTS: The sensitivity, specificity, and accuracy of the combination of the two methods were significantly higher than those using a single method. CONCLUSION: The combination of TI-RADS and USE has high diagnostic sensitivity and accuracy in evaluating the malignant risk of thyroid nodules. PMID- 27183141 TI - Genetics paired with CT angiography in the setting of atherosclerosis. AB - Coronary artery disease (CAD) continues to be the leading cause of morbidity and mortality globally. Although the etiological mechanisms for CAD have not been fully elucidated, however, most would agree that atherosclerotic plaques progressively narrow the coronary arteries are the earliest manifestations and the principal cause of CAD. The emergence of revolutionary imaging technologies such as cardiac CT angiography, noninvasive computed fractional flow reserve and intravascular ultrasound provided the possibility of detecting and monitoring phenotypes associated with subclinical atherosclerosis. Meanwhile, with the widespread use of high-throughput genotyping pipeline such as next-generation sequencing, combined with big data-driven solutions in bioinformatics, translating the emerging genetic technologies into clinical practice and, therefore, provide valuable insight into the CAD study. In this review, we briefly describe the latest noninvasive cardiac imaging techniques for atherosclerosis-related phenotypes' detection, mainly focusing on the coronary artery calcification, plaque burden and stenosis. Furthermore, we highlight the state-of-the-art genotyping techniques and its application in the field of CAD translational study. Finally, we discuss the clinical relevance of genetics paired with noninvasive imaging in the setting of coronary artery atherosclerosis. PMID- 27183142 TI - Is evaluation of placenta with real-time sonoelastography during the second trimester of pregnancy an effective method for the assessment of spontaneous preterm birth risk? AB - PURPOSE: The aim of this study is to investigate the effectiveness of placental strain ratio (SR) values measured by real-time sonoelastography (SE) in the second trimester in the prediction of spontaneous preterm birth (sPTB). METHODS: This study included 70 pregnant women who applied to our clinic for routine second-trimester screening. Placental SR measurements were performed with the SE method. Two different SR measurements were performed by taking two different tissues as references. The SR value measured when taking the rectus abdominis muscle as a reference was termed the muscle-to-placenta strain ratio (MPSR), while the SR value measured when taking subcutaneous tissue as a reference was termed the fat-to-placenta strain ratio (FPSR). Women whose gestational age at birth was less than 37 weeks 0 days were accepted as sPTB. The association between gestational age at birth and MPSR and FPSR was investigated. Receiver operating characteristics analysis was used to calculate the sensitivity and specificity of the elastographic outcomes. RESULTS: There was a low-level negative correlation between MPSR and gestational age at birth (r=-0.300, P=.012) and there was a moderate-level negative correlation between FPSR and gestational age at birth (r=-0.513, P<.001). The multivariate linear regression analysis showed that the FPSR (beta=0.609, P=.002) was the significant predictor for the sPTB. CONCLUSIONS: Our data indicate that the FPSR value measured with real-time SE in the second trimester of pregnancy may be effective in the prediction of sPTB. PMID- 27183144 TI - AFM Imaging of Mercaptobenzoic Acid on Au(110): Submolecular Contrast with Metal Tips. AB - A self-assembled monolayer of mercaptobenzoic acid (MBA) on Au(110) is investigated with scanning tunneling and atomic force microscopy (STM and AFM) and density functional calculations. High-resolution AFM images obtained with metallic tips show clear contrasts between oxygen atoms and phenyl moieties. The contrast above the oxygen atoms is due to attractive covalent interactions, which is different than previously reported high-resolution images, where Pauli repulsion dominated the image contrast. We show that the bonding of MBA to the substrate occurs mainly through dispersion interactions, whereas the thiol-Au bond contributes only a quarter of the adsorption energy. No indication of Au adatoms mediating the thiol-Au interaction was found in contrast to other thiol bonded systems. However, MBA lifts the Au(110)-(2 * 1) reconstruction. PMID- 27183143 TI - Global Profiling of Protein Lysine Malonylation in Escherichia coli Reveals Its Role in Energy Metabolism. AB - Protein lysine malonylation is a recently identified post-translational modification (PTM), which is evolutionarily conserved from bacteria to mammals. Although analysis of lysine malonylome in mammalians suggested that this modification was related to energy metabolism, the substrates and biological roles of malonylation in prokaryotes are still poorly understood. In this study, we performed qualitative and quantitative analyses to globally identify lysine malonylation substrates in Escherichia coli. We identified 1745 malonylation sites in 594 proteins in E. coli, representing the first and largest malonylome data set in prokaryotes up to date. Bioinformatic analyses showed that lysine malonylation was significantly enriched in protein translation, energy metabolism pathways and fatty acid biosynthesis, implying the potential roles of protein malonylation in bacterial physiology. Quantitative proteomics by fatty acid synthase inhibition in both auxotrophic and prototrophic E. coli strains revealed that lysine malonylation is closely associated with E. coli fatty acid metabolism. Protein structural analysis and mutagenesis experiment suggested malonylation could impact enzymatic activity of citrate synthase, a key enzyme in citric acid (TCA) cycle. Further comparative analysis among lysine malonylome, succinylome and acetylome data showed that these three modifications could participate in some similar enriched metabolism pathways, but they could also possibly play distinct roles such as in fatty acid synthesis. These data expanded our knowledge of lysine malonylation in prokaryotes, providing a resource for functional study of lysine malonylation in bacteria. PMID- 27183145 TI - Dual Extraction of Photogenerated Electrons and Holes from a Ferroelectric Sr0.5Ba0.5Nb2O6 Semiconductor. AB - The separation of photogenerated charges is a critical factor in photocatalysis. Recently, anomalous photovoltaic (APV) field effects (Voc ~ 10(3) V/cm) in ferroelectrics, with their strong driving force for charge separation, have attracted much attention in photocatalysis and photoelectrocatalysis. However, it is still unknown whether photogenerated electrons and holes can be simultaneously extracted by the strong driving force toward the surface of ferroelectrics and can become available for surface reactions. This issue becomes critically important in photocatalysis because the surface reaction utilizes both the electrons and holes that reach the surface. In this work, a model lateral symmetric structure, metal/Sr0.5Ba0.5Nb2O6/metal (metal = Ag or Pt), as an electrode was fabricated. The dual extractions of photogenerated electrons and holes on the two opposite metal electrodes were achieved, as revealed by photovoltaic and ferroelectrical hysteresis measurements and photoassisted Kelvin probe force microscopy (KPFM). It was found that the high Schottky barriers of the two opposite Sr0.5Ba0.5Nb2O6-Pt electrodes are key factors that alter the two space charge regions (SCRs) by a poling effect. The resulting built-in electrical fields with parallel directions near both electrodes significantly enhance the charge separation ability. Our model unravels the driving force of charge separation in ferroelectric semiconductors, thus demonstrating the potential for highly efficient charge separation in photocatalysis. PMID- 27183146 TI - Aerogel Microparticles from Oil-in-Oil Emulsion Systems. AB - This paper reports preparation of polymer aerogel microparticles via sol-gel reactions inside micrometer size droplets created in an oil-in-oil emulsion system. The oil-in-oil emulsion system is obtained by dispersing in cyclohexane the droplets of the sols of polybenzoxazine (PBZ) or polyimide (PI) prepared in dimethylformamide. The sol droplets transform into harder gel microparticles due to sol-gel reactions. Finally, the aerogel microparticles are recovered using supercritical drying of the gel microparticles. The PBZ and PI aerogel microparticles prepared in this manner show mean diameter 32.7 and 40.0 MUm, respectively, mesoporous internal structures, and surface area 55.4 and 512.0 m(2)/g, respectively. Carbonization of PBZ aerogel microparticles maintains the mesoporous internal structures but yields narrower pore size distribution. PMID- 27183147 TI - Nucleotide excision repair and response and survival to chemotherapy in colorectal cancer patients. AB - Several new chemotherapeutic agents have become available for the treatment of colorectal cancer, which has led to increased complexity in treatment planning. Treatment decision making for individual patients could be facilitated if guided by predictive and prognostic markers. As most cytotoxic drugs induce DNA damage, the DNA damage repair pathways hold potential for yielding such biomarkers. Here, we review the current evidence of a possible involvement of the nucleotide excision repair pathway in the efficacy of chemotherapeutic agents used in the treatment of colorectal cancer. Although a large number of studies have been conducted, they are generally of moderate size and heterogeneous in design. Up to date no firm conclusions can be drawn to translate these results into the clinic. We recommend further comprehensive investigations of the nucleotide excision repair pathway in large patient studies that include both discovery and validation cohorts. PMID- 27183148 TI - A t(16;21)(p11;q22) in Acute Myeloid Leukemia (AML) Resulting in Fusion of the FUS/TLS and ERG Genes: A Review of the Literature. AB - The t(16;21)(p11;q22) is a rare chromosomal abnormality that appears in approximately 1% of acute myeloid leukemia (AML) cases. Previously, between 50 and 60 cases have been reported. In this review, we will discuss the literature regarding t(16;21) as well as cases published. We compiled 68 cases from the Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer as well as 10 additional cases in the literature, for a total of 78 cases. The t(16;21) results in the TLS(FUS)-ERG fusion protein, which is believed to function as a transcriptional activator in leukemogenesis and has been demonstrated to interfere in normal pre-mRNA splicing functions of FUS/TLS. Reverse-transcriptase polymerase chain reaction of fusion transcripts in patients, has been demonstrated to have diagnostic significance in monitoring for minimal residual disease. Cytogenetically, about half of the cases had secondary chromosomal abnormalities; we found that trisomy 8 and 10 were the most common abnormalities, occurring in 9.1% of the otal cases for each. t(16;21) in AML has been described with various morphological features, such as phagocytosis and vacuolation, and is present in multiple FAB types. Immunophenotypic characteristics such as CD33 and CD34 expression have also been noted, and several studies have examined the relation between CD56 receptor expression and t(16;21) AML. In general, t(16;21) in AML is associated with a poor prognosis and this abnormality could serve as cytogenetic indicator in determining diagnosis and prognosis. Herein, we summarize the cytogenetic features found in the the Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer for t(16;21) in AML, as well as review the current literature associated with t(16;21), AML and its features. PMID- 27183149 TI - 'Two Minds with but a Single Thought ...'. PMID- 27183150 TI - Disruption of the gene C12orf35 leads to increased productivities in recombinant CHO cell lines. AB - Recently, we reported that the loss of a telomeric region of chromosome 8 in Chinese Hamster Ovary (CHO) cells correlates with higher recombinant productivities. New cell lines lacking this region, called CHO-C8DEL, showed several advantages during cell line generation and for the production of recombinant proteins (Ritter et al., 2016, Biotechnol Bioeng). Here, we performed knock-down and knock-out experiments of genes located within this telomeric region of chromosome 8 to identify the genes causing the observed phenotypes of CHO-C8DEL cell lines. We present evidence that loss or reduced expression of the gene C12orf35 is responsible for higher productivities and shorter recovery times during selection pressure. These effects are mediated by increased levels of mRNA of the exogenes heavy chain (HC) and light chain (LC) as well as dihydrofolate reductase (DHFR) and neomycin phosphotransferase (Neo) during the stable expression of antibodies. Biotechnol. Bioeng. 2016;113: 2433-2442. (c) 2016 Wiley Periodicals, Inc. PMID- 27183151 TI - Assessment of Neurocognitive Functions in Children and Adolescents with Obesity. AB - Obesity is linked to adverse neurocognitive outcomes including reduced cognitive functioning. We aimed to investigate the differences in neuropsychological test performance of Turkish children and adolescents with obesity and healthy peers. Study includes 147 children and adolescents ranging in age from 8 to 16 years: 92 with obesity and 55 with healthy controls. After the participants were administered the Children's Depression Inventory (CDI) and the Screen for Child Anxiety Related Disorders (SCARED), they completed the battery tests of the Central Nervous System Vital Signs (CNSVS), a neurocognitive test battery, via computer. The battery calculates seven domain scores (Memory, Psychomotor speed, Processing speed, Reaction time, Complex attention, Executive Function, Cognitive flexibility), and a summary score (Neurocognition Index [NCI]). There was a statistically significant difference between the obesity and control groups on all cognitive domains. The mean NCI score of the obesity group was 81.3 +/- 10.24 compared to 97.29 +/- 4.97 for the control group. The mean NCI score in the obesity group was significantly lower than that of the control group (p < 0.001). The mean scores of other domains of obese patients were also found to be significantly lower than those of the control participants (p < 0.001). The mean SCARED scores of the participants with obesity were found to be significantly higher than those of the control participants (p < 0.05). However, no statistically significant relationship was found between the SCARED and the CNSVS scores. Cognitive dysfunction in children and adolescents with obesity should be taken into consideration when assessing and managing this population. PMID- 27183152 TI - Body representation alterations in personal but not in extrapersonal neglect patients. AB - There is still a matter of debate around the nature of personal neglect. Is it an attention disorder or a body representation disorder? Here we investigate the presence of body representation deficits (i.e., the visuo-spatial body map) in right and left brain-damaged patients and in particular in those affected by personal neglect. 23 unilateral brain-damaged patients (5 left-brain-damaged and 18 right-brain-damaged patients) and 15 healthy controls took part in the study. The visuo-spatial body map was assessed by means of the "Frontal body-evocation subtest (FBE)," in which participants have to put tiles representing body parts on a small wooden board where only the head is depicted as a reference point. In order to compare performance on the FBE with performance on an inanimate object that had well-defined right and left sides, participants also performed the "Car test." Group statistical analysis shows that the performance of patients with personal neglect is significantly worse than that of the controls and patients without personal neglect in the FBE but not in the Car test. Single case analyses of the five patients with pure personal neglect confirm the results of group analysis. Our data supports the hypothesis that personal neglect is a pervasive body representation disorder. PMID- 27183153 TI - Efficacy and safety of 1550-nm fractional laser in the treatment of acne scars in Chinese patients: A split-face comparative study. AB - OBJECTIVE: To evaluate the efficacy and side effects of 1550-nm fractional Er:Glass laser in treating atrophic acne scar. MATERIALS AND METHODS: Thirty Chinese patients aged 18-65 with atrophic acne scars on both cheeks received a split-face treatment, one side with four sessions of treatment with fractional 1550-nm Er:Glass laser at 20-day interval and the other with topical asiaticoside cream application three times daily as control. Clinical response and side effects were evaluated by a dermatologist three weeks after each treatment and again 12 weeks after the last laser treatment. In addition, self-evaluation of satisfaction by the patients was done at the end of treatment. RESULTS: The study found that mean scores decrease after treatment was 5.65 +/- 4.34 for the treated side and 1.23 +/- 3.41 for the control side. The improvement in acne scars after the fractional Er:Glass laser 1550-nm treatment was more significant than the control side (p = 0.0001). The side effects were mainly local skin irritation and erythema, which disappeared within one week. CONCLUSION: The research results show that the fractional 1550-nm Er:Glass laser is an effective and safe treatment device for atrophic acne scars. PMID- 27183154 TI - Do Resting Plasma beta-Endorphin Levels Predict Responses to Opioid Analgesics? AB - OBJECTIVES: Clinically feasible predictors of opioid analgesic responses for use in precision pain medicine protocols are needed. This study evaluated whether resting plasma beta-endorphin (BE) levels predicted responses to an opioid analgesic, and whether chronic pain status or sex moderated these effects. METHODS: Participants included 73 individuals with chronic low back pain (CLBP) and 88 pain-free controls, all using no daily opioid analgesics. Participants attended 2 identical laboratory sessions during which they received either intravenous morphine (0.08 mg/kg) or saline placebo, with blood samples obtained before drug administration to assay resting plasma BE levels. Once peak drug activity was achieved in each session, participants engaged in an ischemic forearm pain task (ISC) and a heat pain task. Morphine analgesic effects were derived reflecting the difference in pain outcomes between placebo and morphine conditions. RESULTS: In hierarchical regressions, significant Type (CLBP vs. control)*BE interactions (Ps<0.05) were noted for morphine effects on ISC tolerance, ISC intratask pain ratings, and thermal VAS unpleasantness ratings. These interactions derived primarily from associations between higher BE levels and smaller morphine effects restricted to the CLBP subgroup. All other BE related effects, including sex interactions, for predicting morphine analgesia failed to reach statistical significance. DISCUSSION: BE was a predictor of morphine analgesia for only 3 out of 9 outcomes examined, with these effects moderated by chronic pain status but not sex. On the whole, results do not suggest that resting plasma BE levels are likely to be a clinically useful predictor of opioid analgesic responses. PMID- 27183165 TI - Antibacterial, Structural and Optical Characterization of Mechano-Chemically Prepared ZnO Nanoparticles. AB - Structural investigations, optical properties and antibacterial performance of the pure Zinc Oxide (ZnO) nanoparticles (NPs) synthesized by mechano-chemical method are presented. The morphology, dimensions and crystallinity of the ZnO NPs were controlled by tweaking the mechanical agitation of the mixture and subsequent thermal treatment. ZnO nanoparticles in small (< 20 nm) dimensions with spherical morphology and narrow size distribution were successfully obtained after treating the mechano-chemically prepared samples at 250 degrees C. However, higher temperature treatments produced larger particles. TEM, XRD and UV-Vis spectroscopy results suggested crystalline and phase pure ZnO. The NPs demonstrated promising antibacterial activity against Gram negative foodborne and waterborne bacterial pathogens i.e. Enteropathogenic E. coli (EPEC), Campylobacter jejuni and Vibrio cholerae as well as Gram positive methicillin resistant Staphylococcus aureus (MRSA), thus potential for medical applications. Scanning electron microscopy and survival assay indicated that most probably ZnO nanoparticles cause changes in cellular morphology which eventually causes bacterial cell death. PMID- 27183166 TI - Lecithin:Retinol Acyltransferase: A Key Enzyme Involved in the Retinoid (visual) Cycle. AB - Lecithin:retinol acyltransferase (LRAT) catalyzes the acyl transfer from the sn-1 position of phosphatidylcholine (PC) to all-trans-retinol, creating fatty acid retinyl esters (palmitoyl, stearoyl, and some unsaturated derivatives). In the eye, these retinyl esters are substrates for the 65 kDa retinoid isomerase (RPE65). LRAT is well characterized biochemically, and recent structural data from closely related family members of the NlpC/P60 superfamily and a chimeric protein have established its catalytic mechanism. Mutations in the LRAT gene are responsible for approximately 1% of reported cases of Leber congenital amaurosis (LCA). Lack of functional LRAT, expressed in the retinal pigmented epithelium (RPE), results in loss of the visual chromophore and photoreceptor degeneration. LCA is a rare hereditary retinal dystrophy with an early onset associated with mutations in one of 21 known genes. Protocols have been devised to identify therapeutics that compensate for mutations in RPE65, also associated with LCA. The same protocols can be adapted to combat dystrophies associated with LRAT. Improvement in the visual function of clinical recipients of therapy with recombinant adeno-associated virus (rAAV) vectors incorporating the RPE65 gene provides a proof of concept for LRAT, which functions in the same cell type and metabolic pathway as RPE65. In parallel, a clinical trial that employs oral 9-cis retinyl acetate to replace the missing chromophore in RPE65 and LRAT causative disease has proven to be effective and free of adverse effects. This article summarizes the biochemistry of LRAT and examines chromophore replacement as a treatment for LCA caused by LRAT mutations. PMID- 27183168 TI - Are We Moving Closer to Noninvasive Imaging and Monitoring of Neonatal Anesthesia induced Neurotoxicity? PMID- 27183170 TI - Mussel-Inspired Polydopamine Coating for Enhanced Thermal Stability and Rate Performance of Graphite Anodes in Li-Ion Batteries. AB - Despite two decades of commercial history, it remains very difficult to simultaneously achieve both high rate capability and thermal stability in the graphite anodes of Li-ion batteries because the stable solid electrolyte interphase (SEI) layer, which is essential for thermal stability, impedes facile Li(+) ion transport at the interface. Here, we resolve this longstanding challenge using a mussel-inspired polydopamine (PD) coating via a simple immersion process. The nanometer-thick PD coating layer allows the formation of an SEI layer on the coating surface without perturbing the intrinsic properties of the SEI layer of the graphite anodes. PD-coated graphite exhibits far better performances in cycling test at 60 degrees C and storage test at 90 degrees C than bare graphite. The PD-coated graphite also displays superior rate capability during both lithiation and delithiation. As evidenced by surface free energy analysis, the enhanced performance of the PD-coated graphite can be ascribed to the Lewis basicity of the PD, which scavenges harmful hydrofluoric acid and forms an intermediate triple-body complex among a Li(+) ion, solvent molecules, and the PD's basic site. The usefulness of the proposed PD coating can be expanded to various electrodes in rechargeable batteries that suffer from poor thermal stability and interfacial kinetics. PMID- 27183169 TI - In Vivo Monitoring of Sevoflurane-induced Adverse Effects in Neonatal Nonhuman Primates Using Small-animal Positron Emission Tomography. AB - BACKGROUND: Animals exposed to sevoflurane during development sustain neuronal cell death in their developing brains. In vivo micro-positron emission tomography (PET)/computed tomography imaging has been utilized as a minimally invasive method to detect anesthetic-induced neuronal adverse effects in animal studies. METHODS: Neonatal rhesus monkeys (postnatal day 5 or 6, 3 to 6 per group) were exposed for 8 h to 2.5% sevoflurane with or without acetyl-L-carnitine (ALC). Control monkeys were exposed to room air with or without ALC. Physiologic status was monitored throughout exposures. Depth of anesthesia was monitored using quantitative electroencephalography. After the exposure, microPET/computed tomography scans using F-labeled fluoroethoxybenzyl-N-(4-phenoxypyridin-3-yl) acetamide (FEPPA) were performed repeatedly on day 1, 1 and 3 weeks, and 2 and 6 months after exposure. RESULTS: Critical physiologic metrics in neonatal monkeys remained within the normal range during anesthetic exposures. The uptake of [F] FEPPA in the frontal and temporal lobes was increased significantly 1 day or 1 week after exposure, respectively. Analyses of microPET images recorded 1 day after exposure showed that sevoflurane exposure increased [F]-FEPPA uptake in the frontal lobe from 0.927 +/- 0.04 to 1.146 +/- 0.04, and in the temporal lobe from 0.859 +/- 0.05 to 1.046 +/- 0.04 (mean +/- SE, P < 0.05). Coadministration of ALC effectively blocked the increase in FEPPA uptake. Sevoflurane-induced adverse effects were confirmed by histopathologic evidence as well. CONCLUSIONS: Sevoflurane-induced general anesthesia during development increases glial activation, which may serve as a surrogate for neurotoxicity in the nonhuman primate brain. ALC is a potential protective agent against some of the adverse effects associated with such exposures. PMID- 27183171 TI - Directing Matter: Toward Atomic-Scale 3D Nanofabrication. AB - Enabling memristive, neuromorphic, and quantum-based computing as well as efficient mainstream energy storage and conversion technologies requires the next generation of materials customized at the atomic scale. This requires full control of atomic arrangement and bonding in three dimensions. The last two decades witnessed substantial industrial, academic, and government research efforts directed toward this goal through various lithographies and scanning probe-based methods. These technologies emphasize 2D surface structures, with some limited 3D capability. Recently, a range of focused electron- and ion-based methods have demonstrated compelling alternative pathways to achieving atomically precise manufacturing of 3D structures in solids, liquids, and at interfaces. Electron and ion microscopies offer a platform that can simultaneously observe dynamic and static structures at the nano- and atomic scales and also induce structural rearrangements and chemical transformation. The addition of predictive modeling or rapid image analytics and feedback enables guiding these in a controlled manner. Here, we review the recent results that used focused electron and ion beams to create free-standing nanoscale 3D structures, radiolysis, and the fabrication potential with liquid precursors, epitaxial crystallization of amorphous oxides with atomic layer precision, as well as visualization and control of individual dopant motion within a 3D crystal lattice. These works lay the foundation for approaches to directing nanoscale level architectures and offer a potential roadmap to full 3D atomic control in materials. In this paper, we lay out the gaps that currently constrain the processing range of these platforms, reflect on indirect requirements, such as the integration of large scale data analysis with theory, and discuss future prospects of these technologies. PMID- 27183167 TI - Immunologic Consequences of Hypoxia during Critical Illness. AB - Hypoxia and immunity are highly intertwined at clinical, cellular, and molecular levels. The prevention of tissue hypoxia and modulation of systemic inflammation are cornerstones of daily practice in the intensive care unit. Potentially, immunologic effects of hypoxia may contribute to outcome and represent possible therapeutic targets. Hypoxia and activation of downstream signaling pathways result in enhanced innate immune responses, aimed to augment pathogen clearance. On the other hand, hypoxia also exerts antiinflammatory and tissue-protective effects in lymphocytes and other tissues. Although human data on the net immunologic effects of hypoxia and pharmacologic modulation of downstream pathways are limited, preclinical data support the concept of tailoring the immune response through modulation of the oxygen status or pharmacologic modulation of hypoxia-signaling pathways in critically ill patients. PMID- 27183172 TI - Collection of Patients' Disability Status by Healthcare Organizations: Patients' Perceptions and Attitudes. AB - Recent policies call for healthcare organizations to consistently document patients' disability status for the purpose of tracking the quality of care experienced by patients with disabilities. The purpose of the study was to explore patients' attitudes toward healthcare organizations collecting disability status. We surveyed a convenience sample of patients in three outpatient clinics, including primary care and rehabilitation clinics. A total of 303 patients participated; 49% self-identified as disabled, 59% were female and the mean age was 52 years. The majority of participants (88%) either agreed or strongly agreed that it is important for healthcare organizations to collect information about disabilities; 77% stated that they were comfortable or very comfortable with healthcare organizations collecting this information. By contrast, we found that almost a quarter of participants had concerns with front desk staff collecting disability status information. When we presented disability questions endorsed by the Health and Human Services Department, over a quarter of participants (28%) felt that the questions were not inclusive of all disability categories. Although patients are supportive of healthcare organizations collecting disability status information, concerns exist regarding how the information is collected and which categories are included, suggesting the need for continued development of evidence-based, patient-centered methods and questions. PMID- 27183173 TI - Nationwide 30-Day Readmissions After Elective Orthopedic Surgery: Reasons and Implications. AB - INTRODUCTION: Reducing readmissions after orthopedic surgery is important for decreasing hospital costs and patient morbidity. Our goals were to establish national rates and reasons for 30-day readmissions after common elective orthopedic procedures. METHODS: Patients undergoing total knee arthroplasty, total hip arthroplasty, posterior lumbar fusion, anterior cervical discectomy and fusion, or total shoulder arthroplasty were identified from the American College of Surgeons National Surgical Quality Improvement Program database. Thirty-day readmission rates, timing, and reasons were recorded for each procedure. Multivariate analysis was used to identify risk factors of readmissions. RESULTS: A total of 3.8% of patients had an all-cause readmission, 3.6% had an unplanned readmission, and 2.4% had an unplanned readmission related to surgery (URRS). The most common reason was surgical site complication followed by venous thromboembolism and bleeding. Only 3.2% of all patients with a URRS were readmitted because of a predischarge complication. Independent predictors of URRS were current smoking, any inpatient complication, and non-home discharge. CONCLUSIONS: Unplanned readmissions were a proxy for new postdischarge complications rather than a re-exacerbation of previous inpatient events. Emphasis should be on more effective prevention strategies for surgical site infections, continuing to prevent inpatient complications and focusing on home discharge. PMID- 27183174 TI - What'S New In Shock, June 2016? PMID- 27183176 TI - A Novel Method for Profiling and Quantifying Short- and Medium-Chain Chlorinated Paraffins in Environmental Samples Using Comprehensive Two-Dimensional Gas Chromatography-Electron Capture Negative Ionization High-Resolution Time-of Flight Mass Spectrometry. AB - Chlorinated paraffins (CPs) are complex technical mixtures containing thousands of isomers. Analyzing CPs in environmental matrices is extremely challenging. CPs have broad, unresolved profiles when analyzed by one-dimensional gas chromatography (GC). Comprehensive two-dimensional GC (GC*GC) can separate CPs with a high degree of orthogonality. A novel method for simultaneously profiling and quantifying short- and medium-chain CPs, using GC*GC coupled with electron capture negative ionization high-resolution time-of-flight mass spectrometry, was developed. The method allowed 48 CP formula congener groups to be analyzed highly selectively in one injection through accurate mass measurements of the [M - Cl]( ) ions in full scan mode. The correlation coefficients (R(2)) for the linear calibration curves for different chlorine contents were 0.982 for short-chain CPs and 0.945 for medium-chain CPs. The method was successfully used to determine CPs in sediment and fish samples. By using this method, with enhanced chromatographic separation and high mass resolution, interferences between CP congeners and other organohalogen compounds, such as toxaphene, are minimized. New compounds, with the formulas C9H14Cl6 and C9H13Cl7, were found in sediment and biological samples for the first time. The method was shown to be a powerful tool for the analysis of CPs in environmental samples. PMID- 27183175 TI - Association of Religious Service Attendance With Mortality Among Women. AB - IMPORTANCE: Studies on the association between attendance at religious services and mortality often have been limited by inadequate methods for reverse causation, inability to assess effects over time, and limited information on mediators and cause-specific mortality. OBJECTIVE: To evaluate associations between attendance at religious services and subsequent mortality in women. DESIGN, SETTING, AND PARTICIPANTS: Attendance at religious services was assessed from the first questionnaire in 1992 through June 2012, by a self-reported question asked of 74 534 women in the Nurses' Health Study who were free of cardiovascular disease and cancer at baseline. Data analysis was conducted from return of the 1996 questionnaire through June 2012. MAIN OUTCOMES AND MEASURES: Cox proportional hazards regression model and marginal structural models with time-varying covariates were used to examine the association of attendance at religious services with all-cause and cause-specific mortality. We adjusted for a wide range of demographic covariates, lifestyle factors, and medical history measured repeatedly during the follow-up, and performed sensitivity analyses to examine the influence of potential unmeasured and residual confounding. RESULTS: Among the 74 534 women participants, there were 13 537 deaths, including 2721 owing to cardiovascular deaths and 4479 owing to cancer deaths. After multivariable adjustment for major lifestyle factors, risk factors, and attendance at religious services in 1992, attending a religious service more than once per week was associated with 33% lower all-cause mortality compared with women who had never attended religious services (hazard ratio, 0.67; 95% CI, 0.62 0.71; P < .001 for trend). Comparing women who attended religious services more than once per week with those who never attend, the hazard ratio for cardiovascular mortality was 0.73 (95% CI, 0.62-0.85; P < .001 for trend) and for cancer mortality was 0.79 (95% CI, 0.70-0.89; P < .001 for trend). Results were robust in sensitivity analysis. Depressive symptoms, smoking, social support, and optimism were potentially important mediators, although the overall proportion of the association between attendance at religious services and mortality was moderate (eg, social support explained 23% of the effect [P = .003], depressive symptoms explained 11% [P < .001], smoking explained 22% [P < .001], and optimism explained 9% [P < .001]). CONCLUSIONS AND RELEVANCE: Frequent attendance at religious services was associated with significantly lower risk of all-cause, cardiovascular, and cancer mortality among women. Religion and spirituality may be an underappreciated resource that physicians could explore with their patients, as appropriate. PMID- 27183177 TI - Critical Review: Review of the Efficacy, Safety, and Pharmacokinetics of Raltegravir in Pregnancy. AB - Raltegravir was previously considered an alternative antiretroviral in pregnancy because of limited data, but recent pregnancy guidelines recommend raltegravir as a preferred integrase treatment option. Data from published articles and preliminary meeting reports between 2001 and July 2015 are reviewed. The literature includes a total of 278 maternal-infant pairs who received raltegravir during pregnancy. The standard raltegravir dose seems safe and effective in preventing mother-to-child transmission in late pregnancy presenters with unknown or unsuppressed viral load, or in multidrug resistance. Viral decay was rapid allowing most women to deliver at undetectable viral levels. Raltegravir was well tolerated, with the exception of a few cases of transient increases in maternal transaminases. No infant adverse effect was consistently reported. Existing data support the use of raltegravir in antiretroviral-naive and experienced pregnant women. PMID- 27183178 TI - Association of Hepatitis C Virus Infection With CD4/CD8 Ratio in HIV-Positive Women. AB - BACKGROUND: Recent studies reported that the CD4/CD8 T-cell ratio is inversely associated with biomarkers traditionally used to measure immune activation and systemic inflammation in highly active antiretroviral therapy-treated HIV infected (HIV+) patients. The relation of hepatitis C virus (HCV) coinfection with the CD4/CD8 ratio in HIV+ patients is unknown. METHODS: We examined 50,201 CD4/CD8 ratios measured over 20 years in 3 groups of HIV+ women enrolled in the Women's Interagency HIV Study: HCV antibody negative (n = 1734), cleared HCV (n = 231), and chronic HCV (n = 751) in multivariate models. IFNL4-DeltaG genotype and HCV viral load were also considered. RESULTS: Compared with HCV antibody negative status, chronic HCV infection was associated with lower CD4/CD8 ratios when HIV viral load was suppressed to the lower limit of quantification (beta = -0.08; P = 0.002). Cleared HCV (beta = -0.10; P = 0.0009), but not IFNL4-DeltaG genotype or HCV viral load, was also associated with lower CD4/CD8 ratios when HIV viral load was suppressed to the lower limit of quantification. CONCLUSIONS: The association of HCV coinfection with CD4/CD8 ratio is consistent with previously observed associations of HCV coinfection with biomarkers traditionally used to measure immune activation and systemic inflammation in HIV+ patients. These data provide additional support for the use of CD4/CD8 ratio for routine monitoring of immune activation and inflammation in HIV+ patients, including those with HIV/HCV coinfection; however, the unexpected association between cleared HCV and lower CD4/CD8 ratio requires additional study. PMID- 27183180 TI - Deoxygenation Increases Photoluminescence Lifetime of Protein-Responsive Organic Probes with Triplet-Singlet Resonant Energy Transfer. AB - Cells and bodily fluids possess strong nanosecond-lifetime autofluorescence, therefore photoluminescent probes with microsecond-scale luminescence decay time would be useful for analysis of biological samples, as they allow the performance of measurements in time-resolved (TR) format in a time gate (time window) where the nonspecific background fluorescence has ceased. We have previously disclosed binding-responsive luminescent probes for protein kinases (PKs), ARC-Lum(Fluo) probes. High brightness of the probes is achieved through intramolecular Forster type resonant energy transfer (FRET) from excited triplet state of a thiophene- or selenophene-comprising phosphor ((3)D*) to singlet acceptor dye ((1)A) leading to amplified emission from the dye. Here, we determined quantum yields (QYs) and oxygen sensitivity of separate phosphorescent donor and fluorescent acceptor and compared these with those of the corresponding ARC-Lum(Fluo) probes both in nonbound and PK-bound states. The microsecond-scale luminescence of free and of PK-bound probes was quenched with different efficiency by molecular oxygen and the luminescence intensity of the probes was substantially increased upon deoxygenation. The brightness of an ARC-Lum(Fluo) probe in PK-bound state was more than 50-fold higher than that of the phosphorescent donor alone. The findings of the study can be used for the construction of bright long-lifetime organic tandem probes. PMID- 27183179 TI - Perinatal nicotine exposure induces myogenic differentiation, but not epithelial mesenchymal transition in rat offspring lung. AB - OBJECTIVE: Perinatal nicotine exposure alters offspring lung structure and function; however, the underlying mechanisms remain incompletely understood. Whether epithelial-mesenchymal transition (EMT), a known contributor to pulmonary pathology, occurs following moderate perinatal nicotine exposure is not known. METHODS: Pregnant, pair-fed Sprague Dawley rat dams received either placebo (diluent) or nicotine [1 mg/kg, subcutaneously] once daily from embryonic day (e) 6 to postnatal day (PND) 21. Generation 1 (F1) and 3 (F3) offspring lungs were isolated at PND 21, and using Western analysis, q-RT-PCR and immunohistochemistry examined for evidence of EMT. To gain further supportive evidence for nicotine induced EMT, embryonic day 19 primary rat lung alveolar type II (ATII) cells were cultured and treated with nicotine for 24 hr. RESULTS: Protein levels of alpha smooth muscle actin, fibronectin, and calponin (myogenic differentiation markers) increased significantly. However, surfactant proteins B and C, and cholinephosphate cytidylyltransferase-alpha (epithelial cell markers), as well as the typical markers of EMT, E-cadherin, N-cadherin, and fibroblast specific protein (FSP)-1, in both F1 and F3 generation lungs, showed no significant change between the nicotine exposed and control dams. Immunostaining of lung sections and data from in vitro treated ATII cells strongly supported the Western data. CONCLUSIONS: Enhanced myogenic molecular profile, without evidence of EMT, as evidenced by the absence of the loss of E-cadherin or gains in N-cadherin and FSP 1, suggest that perinatal nicotine exposure does not result in EMT, but it leads to myogenesis, which predominantly accounts for the lung phenotype seen in perinatally nicotine exposed rat offspring. Pediatr Pulmonol. 2016;51:1142-1150. (c) 2016 Wiley Periodicals, Inc. PMID- 27183181 TI - Yes, You Can: Physicians, Patients, and Firearms. AB - Physicians have unique opportunities to help prevent firearm violence. Concern has developed that federal and state laws or regulations prohibit physicians from asking or counseling patients about firearms and disclosing patient information about firearms to others, even when threats to health and safety may be involved. This is not the case. In this article, the authors explain the statutes in question, emphasizing that physicians may ask about firearms (with rare exceptions), may counsel about firearms as they do about other health matters, and may disclose information to third parties when necessary. The authors then review circumstances under which questions about firearms might be most appropriate if they are not asked routinely. Such circumstances include instances when the patient provides information or exhibits behavior suggesting an acutely increased risk for violence, whether to himself or others, or when the patient possesses other individual-level risk factors for violence, such as alcohol abuse. The article summarizes the literature on current physician practices in asking and counseling about firearms, which are done far less commonly than recommended. Barriers to engaging in those practices, the effectiveness of clinical efforts to prevent firearm-related injuries, and what patients think about such efforts and physicians who engage in them are discussed. Proceeding from the limited available evidence, the authors make specific recommendations on how physicians might counsel their patients to reduce their risk for firearm related death or serious injury. Finally, the authors review the circumstances under which disclosure of patient information about firearms to third parties is supported by regulations implementing the Health Insurance Portability and Accountability Act. PMID- 27183182 TI - Correction: Online Alcohol Assessment and Feedback for Hazardous and Harmful Drinkers: Findings From the AMADEUS-2 Randomized Controlled Trial of Routine Practice in Swedish Universities. PMID- 27183183 TI - KOtBu: A Privileged Reagent for Electron Transfer Reactions? AB - Many recent studies have used KOtBu in organic reactions that involve single electron transfer; in the literature, the electron transfer is proposed to occur either directly from the metal alkoxide or indirectly, following reaction of the alkoxide with a solvent or additive. These reaction classes include coupling reactions of halobenzenes and arenes, reductive cleavages of dithianes, and SRN1 reactions. Direct electron transfer would imply that alkali metal alkoxides are willing partners in these electron transfer reactions, but the literature reports provide little or no experimental evidence for this. This paper examines each of these classes of reaction in turn, and contests the roles proposed for KOtBu; instead, it provides new mechanistic information that in each case supports the in situ formation of organic electron donors. We go on to show that direct electron transfer from KOtBu can however occur in appropriate cases, where the electron acceptor has a reduction potential near the oxidation potential of KOtBu, and the example that we use is CBr4. In this case, computational results support electrochemical data in backing a direct electron transfer reaction. PMID- 27183185 TI - Access Governance for Biobanks: The Case of the BioSHaRE-EU Cohorts. AB - Currently, researchers have to apply separately to individual biobanks if they want to carry out studies that use samples and data from multiple biobanks. This article analyzes the access governance arrangements of the original five biobank members of the Biobank Standardisation and Harmonisation for Research Excellence in the European Union (BioSHaRE-EU) project in Finland, Germany, the Netherlands, Norway, and the United Kingdom to identify similarities and differences in policies and procedures, and consider the potential for internal policy "harmonization." Our analysis found differences in the range of researchers and organizations eligible to access biobanks; application processes; requirements for Research Ethics Committee approval; and terms of Material Transfer Agreements relating to ownership and commercialization. However, the main elements of access are the same across biobanks; access will be granted to bona fide researchers conducting research in the public interest, and all biobanks will consider the scientific merit of the proposed use and it's compatibility with the biobank's objectives. These findings suggest potential areas for harmonization across biobanks. This could be achieved through a single centralized application to a number of biobanks or a system of mutual recognition that places a presumption in favor of access to one biobank if already approved by another member of the same consortium. Biobanking and Biomolecular Resources Research Infrastructure European Research Infrastructure Consortia (BBMRI-ERIC), a European consortium of biobanks and bioresources with its own ethical, legal, and social implications (ELSI) common service, could provide a platform by developing guidelines for harmonized internal processes. PMID- 27183186 TI - Peer support services in the behavioral healthcare workforce: State of the field. AB - OBJECTIVE: This article examines how the history and philosophy of peer support services has shaped current mental health and substance use service delivery systems. The growth of peer-run and recovery community organizations in the changing health care environment are discussed, including issues related to workforce development, funding, relevant policies, and opportunities for expansion. These initiatives are designed to increase access to recovery promoting services. METHODS: We conducted an environmental scan and analysis of peer support services within the behavioral health care field in the United States, with particular attention to initiatives of the Substance Abuse and Mental Health Services Administration. Published manuscripts, policy statements, and reports were reviewed. FINDINGS: There is abundant and growing literature illustrating how peer support services have become an integral component of behavioral health care systems in many states. Peer support services have the potential to increase access to recovery-oriented services for people with mental and substance use disorders served by the public behavioral health care system. Numerous initiatives in various states are being undertaken to build this workforce. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Workforce and financing challenges exist, yet opportunities, including among others those made possible by the Affordable Care Act, will continue to strengthen the peer support workforce within behavioral health service delivery systems. (PsycINFO Database Record PMID- 27183187 TI - Predictors of physical activity in persons with mental illness: Testing a social cognitive model. AB - OBJECTIVE: This study examined whether the social cognitive theory (SCT) model can be used to explain the variance in physical exercise among persons with serious mental illnesses. METHOD: A cross-sectional, correlational design was employed. Participants from community mental health centers and supported housing programs (N = 120) completed 9 measures on exercise, social support, self efficacy, outcome expectations, barriers, and goal-setting. RESULTS: Hierarchical regression tested the relationship between self-report physical activity and SCT determinants while controlling for personal characteristics. The model explained 25% of the variance in exercise. Personal characteristics explained 18% of the variance in physical activity, SCT variables of social support, self-efficacy, outcome expectations, barriers, and goals were entered simultaneously, and they added an r2 change value of .07. Gender (beta = -.316, p = .001) and Brief Symptom Inventory Depression subscale (beta = -2.08, p < .040) contributed significantly to the prediction of exercise. In a separate stepwise multiple regression, we entered only SCT variables as potential predictors of exercise. Goal-setting was the single significant predictor, F(1, 118) = 13.59, p < .01), r2 = .10. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: SCT shows promise as an explanatory model of exercise in persons with mental illnesses. Goal-setting practices, self-efficacy, outcome expectations and social support from friends for exercise should be encouraged by psychiatric rehabilitation practitioners. People with more depressive symptoms and women exercise less. More work is needed on theoretical exploration of predictors of exercise. (PsycINFO Database Record PMID- 27183189 TI - Fathers' postnatal distress, parenting self-efficacy, later parenting behavior, and children's emotional-behavioral functioning: A longitudinal study. AB - Fathers' postnatal distress has been associated with subsequent emotional and behavioral problems for children; however, the mechanisms by which this occurs have received less attention. One potential pathway could be via the negative effects that father mental health problems and parenting self-efficacy (PSE) in the postnatal period have on later parenting behaviors. Using a nationally representative cohort of Australian father-child dyads (N = 3,741), the long-term relationships between fathers' psychological distress and PSE in the postnatal period, parenting behavior when children were aged 4-5 years, and emotional behavioral outcomes for children aged 8-9 years were explored. Path analysis indicated that high distress and low PSE in the postnatal period was associated with higher levels of hostile parenting and lower parenting consistency when children were aged 4-5 years; in turn, these were associated with poorer child outcomes at 8-9 years. These results remained significant after controlling for socioeconomic position, couple relationship quality, mothers' and fathers' mental health, and fathers' concurrent parenting behavior. The pathways among PSE, parenting hostility, parenting consistency, and children's outcomes at age 8-9 years differed for fathers of boys compared with fathers of girls. Results highlight the importance of father-inclusive assessments of postnatal mental health. Support programs targeting new fathers' perceptions of parenting competence may be particularly important for fathers experiencing postnatal distress. For fathers, building a stronger sense of parenting competence in the postnatal period is important for later parenting behavior, which relates to children's emotional and behavioral outcomes during middle childhood. (PsycINFO Database Record PMID- 27183188 TI - Longitudinal associations between relationship quality and coparenting across the transition to parenthood: A dyadic perspective. AB - The couple and coparenting relationship are theorized to influence each other in a reciprocal manner over time. Empirical evidence demonstrates cross-sectional associations between the 2 as well as prospective predictions of coparenting by relationship quality and vice versa. However, less is known about the longitudinal reciprocity between the couple relationship and coparenting from the perspective of both parents. The current study sought to examine longitudinal associations between relationship quality and coparenting support/undermining across the transition to parenthood from a dyadic perspective. Participants were 164 cohabiting heterosexual couples expecting their 1st child, assessed during pregnancy and at 6 and 36 months after birth. Actor partner interdependence modeling was used to examine, for both men and women, (a) stability over time in relationship quality and coparenting, (b) reciprocal associations between relationship quality and coparenting support/undermining, and (c) the gender differences in those associations. Moderate rank-order stability in relationship quality and coparenting support/undermining across the 1st 3 years of parenthood was demonstrated. For women, but not men, findings suggested longitudinal reciprocal associations between relationship quality and coparenting support/undermining. Specifically, our findings suggested that prenatal relationship quality sets the stage for coparenting functioning after birth for both men and women but that coparenting functioning is then connected to subsequent feelings about the romantic relationship for only women. (PsycINFO Database Record PMID- 27183190 TI - Reply. PMID- 27183191 TI - High-Efficiency Selective Electron Tunnelling in a Heterostructure Photovoltaic Diode. AB - A heterostructure photovoltaic diode featuring an all-solid-state TiO2/graphene/dye ternary interface with high-efficiency photogenerated charge separation/transport is described here. Light absorption is accomplished by dye molecules deposited on the outside surface of graphene as photoreceptors to produce photoexcited electron-hole pairs. Unlike conventional photovoltaic conversion, in this heterostructure both photoexcited electrons and holes tunnel along the same direction into graphene, but only electrons display efficient ballistic transport toward the TiO2 transport layer, thus leading to effective photon-to-electricity conversion. On the basis of this ipsilateral selective electron tunnelling (ISET) mechanism, a model monolayer photovoltaic device (PVD) possessing a TiO2/graphene/acridine orange ternary interface showed ~86.8% interfacial separation/collection efficiency, which guaranteed an ultrahigh absorbed photon-to-current efficiency (APCE, ~80%). Such an ISET-based PVD may become a fundamental device architecture for photovoltaic solar cells, photoelectric detectors, and other novel optoelectronic applications with obvious advantages, such as high efficiency, easy fabrication, scalability, and universal availability of cost-effective materials. PMID- 27183192 TI - Detection of periodic motion trajectories: Effects of frequency and radius. AB - Periodic trajectories are an important component of biological motion. Or, Thabet, Wilkinson, and Wilson (2011) studied radial frequency (RF) motion trajectory detection and concluded that, for RF2-5 trajectories, the threshold function paralleled that of static RF patterns. We have extended Or et al.'s (2011) findings to a broader range of RFs (three to 24 cycles) and across a 4 fold range of radii (1 degrees -4 degrees ). We report that (a) thresholds for RF trajectories decrease as a power function of RF for low RF trajectories (three to six cycles) before approaching an asymptote at high RFs (12-24 cycles); (b) detection thresholds for RF trajectories scale proportionally with radius; and (c) there is no lower versus upper field advantage in the parafoveal field for stimuli displaced from fixation on the vertical midline. The results are compared to earlier findings for static RF thresholds, and we argue that our findings support the existence of parallel spatial and temporal processing channels that may contribute to both action perception and production. PMID- 27183193 TI - Accessory stimuli speed reaction times and reduce distraction in a target distractor task. AB - Eye movements in a visual search task are drawn towards items irrelevant to the search (distractors). Advance information about the position or features of distractors can reduce this effect, by speeding the resolution of conflict between search target and distractor. The present study investigated whether this can also be achieved by a prime that merely warns of an impending task without providing any other information (an accessory stimulus). We found that accessory stimuli speed the initiation of a saccade to the target, but also speed the resolution of target-distractor conflict. This finding suggests that the oculomotor system can be prepared to counteract distraction in advance of task onset, without requiring information about a specific spatial location or feature. PMID- 27183195 TI - Structure of the Dcp2-Dcp1 mRNA-decapping complex in the activated conformation. AB - The removal of the mRNA 5' cap (decapping) by Dcp2 shuts down translation and commits mRNA to full degradation. Dcp2 activity is enhanced by activator proteins such as Dcp1 and Edc1. However, owing to conformational flexibility, the active conformation of Dcp2 and the mechanism of decapping activation have remained unknown. Here, we report a 1.6-A-resolution crystal structure of the Schizosaccharomyces pombe Dcp2-Dcp1 heterodimer in an unprecedented conformation that is tied together by an intrinsically disordered peptide from Edc1. In this ternary complex, an unforeseen rotation of the Dcp2 catalytic domain allows residues from both Dcp2 and Dcp1 to cooperate in RNA binding, thus explaining decapping activation by increased substrate affinity. The architecture of the Dcp2-Dcp1-Edc1 complex provides a rationale for the conservation of a sequence motif in Edc1 that is also present in unrelated decapping activators, thus indicating that the presently described mechanism of decapping activation is evolutionarily conserved. PMID- 27183194 TI - Functional interplay between MSL1 and CDK7 controls RNA polymerase II Ser5 phosphorylation. AB - Proper gene expression requires coordinated interplay among transcriptional coactivators, transcription factors and the general transcription machinery. We report here that MSL1, a central component of the dosage compensation complex in Drosophila melanogaster and Drosophila virilis, displays evolutionarily conserved sex-independent binding to promoters. Genetic and biochemical analyses reveal a functional interaction of MSL1 with CDK7, a subunit of the Cdk-activating kinase (CAK) complex of the general transcription factor TFIIH. Importantly, MSL1 depletion leads to decreased phosphorylation of Ser5 of RNA polymerase II. In addition, we demonstrate that MSL1 is a phosphoprotein, and transgenic flies expressing MSL1 phosphomutants show mislocalization of the histone acetyltransferase MOF and histone H4 K16 acetylation, thus ultimately causing male lethality due to a failure of dosage compensation. We propose that, by virtue of its interaction with components of the general transcription machinery, MSL1 exists in different phosphorylation states, thereby modulating transcription in flies. PMID- 27183197 TI - Automated Overnight Closed-Loop Control Using a Proportional-Integral-Derivative Algorithm with Insulin Feedback in Children and Adolescents with Type 1 Diabetes at Diabetes Camp. AB - OBJECTIVE: This study determined the feasibility and efficacy of an automated proportional-integral-derivative with insulin feedback (PID-IFB) controller in overnight closed-loop (OCL) control of children and adolescents with type 1 diabetes over multiple days in a diabetes camp setting. RESEARCH DESIGN AND METHODS: The Medtronic (Northridge, CA) AndroidTM (Google, Mountain View, CA) based PID-IFB system consists of the Medtronic Minimed RevelTM 2.0 pump and EnliteTM sensor, a control algorithm residing on an Android phone, a translator, and remote monitoring capabilities. An inpatient study was completed for 16 participants to determine feasibility. For the camp study, subjects with type 1 diabetes were randomized to either OCL or sensor-augmented pump therapy (control conditions) per night for up to 6 nights at diabetes camp. RESULTS: During the camp study, 21 subjects completed 50 OCL nights and 52 control nights. Based on intention to treat, the median time spent in range, from 70 to 150 mg/dL, was greater during OCL at 66.4% (n = 55) versus 50.6% (n = 52) during the control period (P = 0.004). A per-protocol analysis allowed for assessment of algorithm performance with the median percentage time in range, 70-150 mg/dL, being 75.5% (n = 37) for OCL versus 47.6% (n = 32) for the control period (P < 0.001). There was less time spent in the hypoglycemic ranges <60 mg/dL and <70 mg/dL during OCL compared with the control period (P = 0.003 and P < 0.001, respectively). CONCLUSIONS: The PID-IFB controller is effective in improving time spent in range as well as reducing nocturnal hypoglycemia during the overnight period in children and adolescents with type 1 diabetes in a diabetes camp setting. PMID- 27183196 TI - Mechanism of extracellular ion exchange and binding-site occlusion in a sodium/calcium exchanger. AB - Na(+)/Ca(2+) exchangers use the Na(+) electrochemical gradient across the plasma membrane to extrude intracellular Ca(2+) and play a central role in Ca(2+) homeostasis. Here, we elucidate their mechanisms of extracellular ion recognition and exchange through a structural analysis of the exchanger from Methanococcus jannaschii (NCX_Mj) bound to Na(+), Ca(2+) or Sr(2+) in various occupancies and in an apo state. This analysis defines the binding mode and relative affinity of these ions, establishes the structural basis for the anticipated 3:1 Na(+)/Ca(2+) exchange stoichiometry and reveals the conformational changes at the onset of the alternating-access transport mechanism. An independent analysis of the dynamics and conformational free-energy landscape of NCX_Mj in different ion-occupancy states, based on enhanced-sampling molecular dynamics simulations, demonstrates that the crystal structures reflect mechanistically relevant, interconverting conformations. These calculations also reveal the mechanism by which the outward to-inward transition is controlled by the ion occupancy, thereby explaining the emergence of strictly coupled Na(+)/Ca(2+) antiport. PMID- 27183199 TI - Hsp60 expression profiles in the reef-building coral Seriatopora caliendrum subjected to heat and cold shock regimes. AB - Climate changes have increased the intensity/frequency of extreme thermal events, which represent serious threats to the health of reef-building corals. Since the vulnerability of corals exposed to thermal stresses are related to their ability to regulate Heat shock proteins (Hsps), we have analyzed together the time related expression profiles of the mitochondrial Hsp60 and the associated changes in tissue pigmentation in Seriatopora caliendrum subjected to 48 h of heat and cold treatments characterized by moderate (+/-2 degrees C) and severe (+/-6 degrees C) shocks. For the first time, an Hsp60 response was observed in a scleractinian coral exposed to cold stresses. Furthermore, the Hsp60 modulations and the changes in the tissue coloration were found to be specific for each treatment. A strong down-regulation at the end of the treatments was observed following both the severe shocks, but only the severe heat stress led to bleaching in concert with the lowest levels of Hsp60, suggesting that a severe heat shock can be more deleterious than an exposure to a severe cold temperature. On the contrary, a moderate cold stress seems to be more harmful than a moderate temperature increase, which could allow coral acclimation. Our results can provide a potential framework for understanding the physiological tolerance of corals under possible future climate changes. PMID- 27183198 TI - Groove model of tibia-femoral osteoarthritis in the rat. AB - Several experimental models of osteoarthritis in rats are used to study the pathophysiology of osteoarthritis. Many mechanically induced models have the limitation that permanent joint instability is induced by, for example, ligament transection or meniscal damage. This permanent instability will counteract the potential beneficial effects of therapy. The groove model of osteoarthritis uses a one-time trigger, surgically induced cartilage damage on the femoral condyles, and has been validated for the canine tibia-femoral compartment. The present study evaluates this model for the rat knee joint. The articular cartilage of the weight bearing surface of both femoral condyles and trochlea were damaged (grooved) without damaging the underlying subchondral bone. Severity of joint degeneration was histologically assessed, in addition to patella cartilage damage, and subchondral bone characteristics by means of (contrast-enhanced) micro-CT. Mild histological degeneration of the surgically untouched tibial plateau cartilage was observed in addition to damage of the femoral condyles, without clear synovial tissue inflammation. Contrast enhanced micro-CT demonstrated proteoglycan loss of the surgically untouched patella cartilage. Besides, a more sclerotic structure of the subchondral bone was observed. The tibia-femoral groove model in a rat results in mild knee joint degeneration, without permanent joint instability and joint inflammation. This makes the rat groove model a useful model to study the onset and progression of post-traumatic non-inflammatory osteoarthritis, creating a relatively sensitive model to study disease modifying osteoarthritic drugs. (c) 2016 The Authors. Journal of Orthopaedic Research published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. J Orthop Res 35:496-505, 2017. PMID- 27183200 TI - Toxic effects of cisplatin cytostatic drug in mussel Mytilus galloprovincialis. AB - Antineoplastic drugs used in chemotherapy were detected in aquatic environment: despite the very low concentrations (ng L(-1) to ug L(-1)), due to their potent mechanism of action they could have adverse effects on non-target aquatic organisms particularly under chronic exposure. Cisplatin (CDDP) is one of the most effective anticancer drug currently in use but information on its ecotoxicological effects is very limited. In this study, Mytilus galloprovincialis was used to investigate the toxic effects related to CDDP exposure. Mussels were exposed to cisplatin (100 ng L(-1)) for 14 days: antioxidant (superoxide dismutase, catalase, total and selenium-dependent glutathione peroxidase) and phase II (glutathione-S-transferase) enzymes activities, oxidative damage (lipid peroxidation), genotoxicity (DNA damage) and neurotoxicity (acetylcholinesterase) was evaluated. Results indicate that CDDP at tested concentration induce changes in the antioxidant capacity, oxidative stress in target organs (digestive gland and gills) as well as DNA damage in mussel hemocytes and neurotoxicity representing a risk for non-target organisms. PMID- 27183204 TI - ApoA1 and ApoA1-specific self-antibodies in cardiovascular disease. AB - Apolipoprotein A1 (ApoA1) is a main protein moiety in high-density lipoprotein (HDL) particles. Generally, ApoA1 and HDL are considered as atheroprotective. In prooxidant and inflammatory microenvironment in the vicinity to the atherosclerotic lesion, ApoA1/HDL are subjected to modification. The chemical modifications such as oxidation, nitration, etc result in altering native architecture of ApoA1 toward dysfunctionality and abnormality. Neutrophil myeloperoxidase has a prominent role in this mechanism. Neo-epitopes could be formed and then exposed that makes them immunogenic. Indeed, these epitopes may be recognized by immune cells and induce production of proatherogenic ApoA1 specific IgG antibodies. These antibodies are biologically relevant because they are able to react with Toll-like receptor (TLR)-2 and TLR4 in target cells and induce a variety of pro-inflammatory responses. Epidemiological and functional studies underline a prognostic value of ApoA1 self-antibodies for several cardiovascular diseases, including myocardial infarction, acute coronary syndrome, and severe carotid stenosis. PMID- 27183205 TI - Downregulation of c-Myc is involved in TLR3-mediated tumor death of neuroblastoma xenografts. AB - Neuroblastoma (NB) is the deadliest pediatric solid tumor due to its pleomorphic molecular characteristics. In the innate immune system, toll-like receptor 3 (TLR3) recognizes viral double-stranded RNAs to initiate immune signaling. Positive TLR3 expression indicates a favorable prognosis in NB patients, and is associated with MYCN-non-amplified. However, TLR3-mediated innate immune responses remain elusive in NB. In this study, we attempted to dissect the molecular mechanism underlying TLR3-agonist polyinosinic-polycytidylic acid [poly(I:C)] treatment in NB in vivo. We established NB xenograft models in non obese diabetic/severe combined immunodeficiency (NOD/SCID) mice with MYCN amplified SK-N-DZ (DZ) cells or MYCN-non-amplified SK-N-AS (AS) cells. Poly(I:C) treatment led to significant tumor regression in AS xenografts, but not in DZ xenografts. Through immunohistochemical analysis, significant suppression of tumor proliferation, downregulation of c-Myc expression, and upregulation of TLR3 expression were found in the treatment group. Poly(I:C) inducing activation of TLR3/IRF3-mediated innate immunity associated with downregulation of c-Myc can be found in MYCN-non-amplified SK-N-AS cells, but not in MYCN-amplified BE(2)-M17 cells. Knockdown of TLR3 disturbed poly(I:C)-induced suppression of c-Myc and upregulation of p-IRF3 in AS cells. Furthermore, poly(I:C) treatment upregulated active NF-kappaB, mitochondrial antioxidant manganese superoxide dismutase and 8 hydroxydeoxyguanosine, which works with reactive oxygen species (ROS) generation and DNA damage. Upregulation of active caspase 3 and cleaved poly [ADP-ribose] polymerase 1 were found in poly(I:C)-treated AS xenografts, which indicates the induction of apoptosis. Thus, our results suggest that c-Myc overexpression may increase sensitivity to poly(I:C)-induced tumor growth arrest and ROS-mediated apoptosis in NB. This study demonstrates that c-Myc protein expression has an important role in TLR3-induced innate immune responses, providing future treatment recommendations. PMID- 27183207 TI - Influence of heteroaggregation processes between intrinsic colloids and carrier colloids on cerium(III) mobility through fractured carbonate rocks. AB - Colloid facilitated transport of radionuclides has been implicated as a major transport vector for leaked nuclear waste in the subsurface. Sorption of radionuclides onto mobile carrier colloids such as bentonite and humic acid often accelerates their transport through saturated rock fractures. Here, we employ column studies to investigate the impact of intrinsic, bentonite and humic acid colloids on the transport and recovery of Ce(III) through a fractured chalk core. Ce(III) recovery where either bentonite or humic colloids were added was 7.7 26.9% Ce for all experiments. Greater Ce(III) recovery was observed when both types of carrier colloids were present (25.4-37.4%). When only bentonite colloids were present, Ce(III) appeared to be fractionated between chemical sorption to the bentonite colloid surfaces and heteroaggregation of bentonite colloids with intrinsic carbonate colloids, precipitated naturally in solution. However, scanning electron microscope (SEM) images and colloid stability experiments reveal that in suspensions of humic acid colloids, colloid-facilitated Ce(III) migration results only from the latter attachment mechanism rather than from chemical sorption. This observed heteroaggregation of different colloid types may be an important factor to consider when predicting potential mobility of leaked radionuclides from geological repositories for spent fuel located in carbonate rocks. PMID- 27183206 TI - Neuropathologic Associations of Learning and Memory in Primary Progressive Aphasia. AB - IMPORTANCE: The dementia syndrome of primary progressive aphasia (PPA) can be caused by 1 of several neuropathologic entities, including forms of frontotemporal lobar degeneration (FTLD) or Alzheimer disease (AD). Although episodic memory is initially spared in this syndrome, the subtle learning and memory features of PPA and their neuropathologic associations have not been characterized. OBJECTIVE: To detect subtle memory differences on the basis of autopsy-confirmed neuropathologic diagnoses in PPA. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis was conducted at the Northwestern Cognitive Neurology and Alzheimer's Disease Center in August 2015 using clinical and postmortem autopsy data that had been collected between August 1983 and June 2012. Thirteen patients who had the primary clinical diagnosis of PPA and an autopsy-confirmed diagnosis of either AD (PPA-AD) or a tau variant of FTLD (PPA FTLD) and 6 patients who had the clinical diagnosis of amnestic dementia and autopsy-confirmed AD (AMN-AD) were included. MAIN OUTCOMES AND MEASURES: Scores on the effortless learning, delayed retrieval, and retention conditions of the Three Words Three Shapes test, a specialized measure of verbal and nonverbal episodic memory. RESULTS: The PPA-FTLD (n = 6), PPA-AD (n = 7), and AMN-AD (n = 6) groups did not differ by demographic composition (all P > .05). The sample mean (SD) age was 64.1 (10.3) years at symptom onset and 67.9 (9.9) years at Three Words Three Shapes test administration. The PPA-FTLD group had normal (ie, near-ceiling) scores on all verbal and nonverbal test conditions. Both the PPA-AD and AMN-AD groups had deficits in verbal effortless learning (mean [SD] number of errors, 9.9 [4.6] and 14.2 [2.0], respectively) and verbal delayed retrieval (mean [SD] number of errors, 6.1 [5.9] and 12.0 [4.4], respectively). The AMN-AD group had additional deficits in nonverbal effortless learning (mean [SD] number of errors, 10.3 [4.0]) and verbal retention (mean [SD] number of errors, 8.33 [5.2]), which were not observed in the PPA-FTLD or PPA-AD groups (all P < .005). CONCLUSIONS AND RELEVANCE: This study identified neuropathologic associations of learning and memory in autopsy-confirmed cases of PPA. Among patients with clinical PPA syndrome, AD neuropathology appeared to interfere with effortless learning and delayed retrieval of verbal information, whereas FTLD-tau pathology did not. The results provide directions for future research on the interactions between limbic and language networks. PMID- 27183208 TI - Attenuation of pharmaceuticals and their transformation products in a wastewater treatment plant and its receiving river ecosystem. AB - Pharmaceuticals are designed to improve human and animal health, but may also be a threat to freshwater ecosystems, particularly after receiving urban or wastewater treatment plant (WWTP) effluents. Knowledge on the fate and attenuation of pharmaceuticals in engineered and natural ecosystems is rather fragmented, and comparable methods are needed to facilitate the comprehension of those processes amongst systems. In this study the dynamics of 8 pharmaceuticals (acetaminophen, sulfapyridine, sulfamethoxazole, carbamazepine, venlafaxine, ibuprofen, diclofenac, diazepam) and 11 of their transformation products were investigated in a WWTP and the associated receiving river ecosystem. During 3 days, concentrations of these compounds were quantified at the influents, effluents, and wastage of the WWTP, and at different distances downstream the effluent at the river. Attenuation (net balance between removal and release from and to the water column) was estimated in both engineered and natural systems using a comparable model-based approach by considering different uncertainty sources (e.g. chemical analysis, sampling, and flow measurements). Results showed that pharmaceuticals load reduction was higher in the WWTP, but attenuation efficiencies (as half-life times) were higher in the river. In particular, the load of only 5 out of the 19 pharmaceuticals was reduced by more than 90% at the WWTP, while the rest were only partially or non-attenuated (or released) and discharged into the receiving river. At the river, only the load of ibuprofen was reduced by more than 50% (out of the 6 parent compounds present in the river), while partial and non-attenuation (or release) was observed for some of their transformation products. Linkages in the routing of some pharmaceuticals (venlafaxine, carbamazepine, ibuprofen and diclofenac) and their corresponding transformation products were also identified at both WWTP and river. Finally, the followed procedure showed that dynamic attenuation in the coupled WWTP-river system could be successfully predicted with simple first order attenuation kinetics for most modeled compounds. PMID- 27183210 TI - Student support and perceptions of urine source separation in a university community. AB - Urine source separation, i.e., the collection and treatment of human urine as a separate waste stream, has the potential to improve many aspects of water resource management and wastewater treatment. However, social considerations must be taken into consideration for successful implementation of this alternative wastewater system. This work evaluated the perceptions of urine source separation held by students living on-campus at a major university in the Southeastern region of the United States. Perceptions were evaluated in the context of the Theory of Planned Behavior. The survey population represents one group within a community type (universities) that is expected to be an excellent testbed for urine source separation. Overall, respondents reported high levels of support for urine source separation after watching a video on expected benefits and risks, e.g., 84% indicated that they would vote in favor of urine source separation in residence halls. Support was less apparent when measured by willingness to pay, as 33% of respondents were unwilling to pay for the implementation of urine source separation and 40% were only willing to pay $1 to $10 per semester. Water conservation was largely identified as the most important benefit of urine source separation and there was little concern reported about the use of urine-based fertilizers. Statistical analyses showed that one's environmental attitude, environmental behavior, perceptions of support within the university community, and belief that student opinions have an impact on university decision makers were significantly correlated with one's support for urine source separation. This work helps identify community characteristics that lend themselves to acceptance of urine source separation, such as those related to environmental attitudes/behaviors and perceptions of behavioral control and subjective norm. Critical aspects of these alternative wastewater systems that require attention in order to foster public acceptance after implementation are also highlighted, such as convenient and aesthetically pleasing methods for waterless toilet paper disposal. PMID- 27183209 TI - High-rate activated sludge communities have a distinctly different structure compared to low-rate sludge communities, and are less sensitive towards environmental and operational variables. AB - High-rate activated sludge processes allow for the recovery of organics and energy from wastewaters. These systems are operated at a short sludge retention time and high sludge-specific loading rates, which results in a higher sludge yield and better digestibility than conventional, low-rate activated sludge. Little is known about the microbial ecology of high-rate systems. In this work, we address the need for a fundamental understanding of how high-rate microbial communities differ from low-rate communities. We investigated the high-rate and low-rate communities in a sewage treatment plant in relation to environmental and operational variables over a period of ten months. We demonstrated that (1) high rate and low-rate communities are distinctly different in terms of richness, evenness and composition, (2) high-rate community dynamics are more variable and less shaped by deterministic factors compared to low-rate communities, (3) sub communities of continuously core and transitional members are more shaped by deterministic factors than the continuously rare members, both in high-rate and low-rate communities, and (4) high-rate community members showed a co-occurrence pattern similar to that of low-rate community members, but were less likely to be correlated to environmental and operational variables. These findings provide a basis for further optimization of high-rate systems, in order to facilitate resource recovery from wastewater. PMID- 27183211 TI - Low temperature acclimation with electrical stimulation enhance the biocathode functioning stability for antibiotics detoxification. AB - Improvement of the stability of functional microbial communities in wastewater treatment system is critical to accelerate pollutants detoxification in cold regions. Although biocathode communities could accelerate environmental pollutants degradation, how to acclimate the cold stress and to improve the catalytic stability of functional microbial communities are remain poorly understood. Here we investigated the structural and functional responses of antibiotic chloramphenicol (CAP) reducing biocathode communities to constant low temperature 10 degrees C (10-biocathode) and temperature elevation from 10 degrees C to 25 degrees C (S25-biocathode). Our results indicated that the low temperature acclimation with electrical stimulation obviously enhanced the CAP nitro group reduction efficiency when comparing the aromatic amine product AMCl2 formation efficiency with the 10-biocathode and S25-biocathode under the opened and closed circuit conditions. The 10-biocathode generated comparative AMCl maximum as the S25-biocathode but showed significant lower dehalogenation rate of AMCl2 to AMCl. The continuous low temperature and temperature elevation both enriched core functional community in the 10-biocathode and S25-biocathode, respectively. The 10-biocathode functioning stability maintained mainly through selectively enriching cold-adapted functional species, coexisting metabolically similar nitroaromatics reducers and maintaining the relative abundance of key electrons transfer genes. This study provides new insights into biocathode functioning stability for accelerating environmental pollutants degradation in cold wastewater system. PMID- 27183212 TI - Metabolomic study of aging in mouse plasma by gas chromatography-mass spectrometry. AB - Metabolomic analysis of aging was performed in plasma samples of young (8 weeks) and old (72 weeks) mice as ethoxycarbonyl/methoxime/tert-butyldimethylsilyl derivatives by gas chromatography-mass spectrometry (GC-MS). As new approaches, study of altered metabolism from aging was attempted by simultaneous profiling analysis of amino acids (AAs), organic acids (OAs) and fatty acids (FAs) by GC-MS in a single run combined with pattern analysis. As a result, 27 amino acids (AAs), 17 organic acids (OAs) and 24 fatty acids (FAs) were positively screened with large variations in plasma samples. Among altered metabolites, levels of six AAs (proline, methionine, 4-hydroxyproline, pipecolic acid, glutamic acid, alpha aminoadipic acid) as neurotransmetters and nutrients, five OAs (2-hydroxybutyric acid, 2-hydroxyglutaric acid, cis-aconitic acid citric acid, isocitric acid) including intermediate metabolites in the TCA cycle, and three n-3 polyunsaturated FAs (PUFAs) of alpha-octadecatrienoic acid, eicosapentaenoic acid and docosahexaenoic acid as potential biomarkers were significantly different between young and old groups. Their levels were normalized to the corresponding mean values of the young group and then plotted into star symbol patterns, which were clearly distinct compared with numerical data and readily distinguishable for young and old groups. Thus, the present metabolomic screening and the star pattern recognition method might be useful for understanding the complexity of biochemical events in aging. PMID- 27183213 TI - Biotransformation and metabolic profile of buddleoside with human intestinal microflora by ultrahigh-performance liquid chromatography coupled to hybrid linear ion trap/orbitrap mass spectrometer. AB - Buddleoside (also known as linarin) as the major flavonoid in Chrysanthemum morifolium Ramat., has been reported to possess a wide range of pharmacological activities. The human intestinal microbiota might have an important impact on drug metabolism and ultimately on the drug oral bioavailability. However, the interaction of the buddleoside with human intestinal bacteria remains unknown. In this study, the conversion of buddleoside by different bacteria from human feces was firstly investigated. A reliable, sensitive and rapid analytical method, ultra performance liquid chromatography was established and successfully applied to investigate the metabolites and metabolic profile of buddleoside by human intestinal bacteria. Among the isolated bacteria, four strains including Escherichia sp. 4, Escherichia sp. 34, Enterococcus sp. 45 and Bacillus sp. 46 showed more powerful conversion capability. Based on the accurate mass data and the characteristic MS(n) product ions, the parent and six metabolites were detected and tentatively identified compared with blank samples. The metabolites were produced by four main metabolic pathways including deglycosylation, acetylation, methylation and hydroxylation. Buddleoside could be firstly converted to its aglycon acacetin (M2) by the majority of the isolated intestinal bacteria. Subsequently, M2 was further metabolize to its methylated (M3), acetylated (M4), hydroxylated (M5) and hydrogenated product (M6). However, acacetin-7-glucosid (M1) was obtained only from the minor bacterial samples like Bacillus sp. 46. To further explain the metabolism of buddleoside, the beta-d glucosidase and alpha-l-rhamnosidase activities of four strains were analyzed. Bacillus sp. 46 could only produce alpha-l-rhamnosidase, while the other three strains showed two kinds of enzyme activities. Furthermore, the activities of alpha-l-rhamnosidase and beta-d-glucosidase reached the highest level at 12-18h and 10-12h, respectively. The metabolic routes and metabolites of buddleoside produced by human intestinal microflora were firstly reported in this paper. The results will be very helpful for the further investigation of the pharmacokinetic research of buddleoside and to unravel how it works in vivo. PMID- 27183215 TI - Simultaneous determination of nine coumarins in rat plasma by HPLC-MS/MS for pharmacokinetics studies following oral administration of Fraxini Cortex extract. AB - A high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed for the simultaneous determination of nine coumarins including aesculin, aesculetin, fraxin, fraxetin, scopoletin, isoscopoletin, 6 hydroxy-7,8-dimethoxy coumarin, 8-hydroxy-6,7-dimethoxy coumarin and umbelliferone in rat plasma using nodakenin as the internal standard (IS). The plasma samples were pretreated by a one-step direct protein precipitation with methanol. The chromatographic separation was carried out on a C18 column with a gradient mobile phase consisting of methanol and water (containing 0.05% acetic acid). All analytes and IS were quantitated through electrospray ionization in negative ion multiple reaction monitoring (MRM) mode. This method was fully validated in terms of the sensitivity, specificity, accuracy, precision (intra- and inter-day), matrix effect, recovery as well as the stability of the analyte under various conditions, and the results satisfied the requirements of biological sample measurement. The validated method was successfully applied to pharmacokinetic study of the nine coumarins in rat plasma after oral administration of Fraxini Cortex aqueous extract, among which the pharmacokinetics of four coumarins including fraxetin, isoscopoletin, 6-hydroxy 7,8-dimethoxy coumarin and 8-hydroxy-6,7-dimethoxy coumarin were studied for the first time. PMID- 27183214 TI - Purification of a fibrinolytic protease from Mucor subtilissimus UCP 1262 by aqueous two-phase systems (PEG/sulfate). AB - A fibrinolytic protease from M. subtilissimus UCP 1262 was recovered and partially purified by polyethylene glycol (PEG)/sodium sulfate aqueous two-phase systems (ATPS). The simultaneous influence of PEG molar mass, PEG concentration and sulfate concentration on the enzyme recovery was first investigated using a 2(3) full factorial design, and the Response Surface Methodology used to identify the optimum conditions for enzyme extraction by ATPS. Once the best PEG molar mass for the process had been selected (6000g/mol), a two-factor central composite rotary design was applied to better evaluate the effects of the other two independent variables. The fibrinolytic enzyme was shown to preferentially partition to the bottom phase with a partition coefficient (K) ranging from 0.2 to 0.7. The best results in terms of enzyme purification were obtained with the system formed by 30.0% (w/w) PEG 6000g/mol and 13.2% (w/w) sodium sulfate, which ensured a purification factor of 10.0, K of 0.2 and activity yield of 102.0%. SDS PAGE and fibrin zymography showed that the purified protease has a molecular mass of 97kDa and an apparent isoelectric point of 5.4. When submitted to assays with different substrates and inhibitors, it showed selectivity for succinyl-l-ala-ala pro-l-phenylalanine-p-nitroanilide and was almost completely inhibited by phenylmethylsulfonyl fluoride, behaving as a chymotrypsin-like protease. At the optimum temperature of 37 degrees C, the enzyme residual activity was 94 and 68% of the initial one after 120 and 150min of incubation, respectively. This study demonstrated that M. subtilissimus protease has potent fibrinolytic activity compared with similar enzymes produced by solid-state fermentation, therefore it may be used as an agent for the prevention and therapy of thrombosis. Furthermore, it appears to have the advantages of low cost production and simple purification. PMID- 27183216 TI - Activation of the pluripotency factor OCT4 in smooth muscle cells is atheroprotective. AB - Although somatic cell activation of the embryonic stem cell (ESC) pluripotency factor OCT4 has been reported, this previous work has been controversial and has not demonstrated a functional role for OCT4 in somatic cells. Here we demonstrate that smooth muscle cell (SMC)-specific conditional knockout of Oct4 in Apoe(-/-) mice resulted in increased lesion size and changes in lesion composition that are consistent with decreased plaque stability, including a thinner fibrous cap, increased necrotic core area, and increased intraplaque hemorrhage. Results of SMC-lineage-tracing studies showed that these effects were probably the result of marked reductions in SMC numbers within lesions and SMC investment within the fibrous cap, which may result from impaired SMC migration. The reactivation of Oct4 within SMCs was associated with hydroxymethylation of the Oct4 promoter and was hypoxia inducible factor-1alpha (HIF-1alpha, encoded by HIF1A) and Kruppel like factor-4 (KLF4)-dependent. These results provide the first direct evidence that OCT4 has a functional role in somatic cells, and they highlight the potential role of OCT4 in normal and diseased somatic cells. PMID- 27183219 TI - Controlled attenuation parameter is correlated with actual hepatic fat content in patients with non-alcoholic fatty liver disease with none-to-mild obesity and liver fibrosis. AB - AIM: Non-invasive steatosis-quantifying methods are required for non-alcoholic fatty liver disease (NAFLD) patients in order to monitor disease severity and assess therapeutic efficacy. Controlled attenuation parameter (CAP) evaluated with vibration-controlled transient elastography can predict the presence of steatosis, but its application to absolute hepatic fat quantitation remains unclear. The aim of this st?udy was to examine whether CAP is correlated with real hepatic fat content in NAFLD patients. METHODS: Eighty-two NAFLD patients who had undergone percutaneous liver biopsy were enrolled. CAP was measured using FibroScan((r)) just before liver biopsy. The percentage of fat droplet area to hepatocyte area in biopsied specimen was determined morphometrically using computerized optical image analyzing system. The correlation between CAP and liver histology was examined. RESULTS: CAP showed an excellent correlation with actual liver fat percentage in the NAFLD patients with body mass index (BMI) of less than 28 kg/m(2) (r = 0.579, P < 0.0001), especially less than 25 kg/m(2) (r = 0.708, P < 0.01), but the meaningful correlation disappeared in the patients with BMI of 28 kg/m(2) or more. In the patients with BMI of less than 28 kg/m(2) , CAP quantitativeness was affected by the presence of stage 2-4 fibrosis, but not the presence of hepatocyte ballooning and severity of lobular inflammation. CONCLUSION: CAP may be a promising tool for quantifying hepatic fat content in NAFLD patients with none-to-mild obesity and liver fibrosis. Further improvement of CAP performance is needed for the NAFLD patients with BMI of more than 28 kg/m(2) or significant hepatic fibrosis. PMID- 27183218 TI - Platelet-derived CXCL4 regulates neutrophil infiltration and tissue damage in severe acute pancreatitis. AB - Platelets are known to play an important role in acute pancreatitis (AP) via promotion of neutrophil accumulation, although mechanisms behind platelet dependent accumulation of neutrophils in the pancreas remain elusive. Platelets contain a wide spectrum of different pro-inflammatory compounds, such as chemokines. CXCL4 (platelet factor 4) is one of the most abundant chemokine in platelets, and we hypothesized that CXCL4 might be involved in platelet-dependent accumulation of neutrophils in the inflamed pancreas. The aim of this study was to examine the role of CXCL4 in severe AP. Pancreatitis was provoked by infusion of taurocholate into the pancreatic duct or by intraperitoneal administration of L-arginine in C57BL/6 mice. Animals were treated with an antibody against platelets or CXCL4 before induction of pancreatitis. Plasma and lung levels of CXCL2, CXCL4, and interleukin (IL)-6 were determined by use of enzyme-linked immunosorbent assay. Flow cytometry was used to examine surface expression of macrophage-1 (Mac-1) on neutrophils. Plasma was obtained from healthy individuals (controls) and patients with AP. Challenge with taurocholate increased plasma levels of CXCL4, and depletion of platelets markedly reduced plasma levels of CXCL4 indicating that circulating levels of CXCL4 are mainly derived from platelets in AP. Inhibition of CXCL4 reduced taurocholate-induced neutrophil recruitment, IL-6 secretion, edema formation, amylase release, and tissue damage in the pancreas. However, immunoneutralization of CXCL4 had no effect on CXCL2 evoked neutrophil expression of Mac-1 or chemotaxis in vitro, suggesting an indirect effect of CXCL4 on neutrophil recruitment in AP. Targeting CXCL4 significantly attenuated plasma and lung levels of CXCL2, which is a potent neutrophil chemoattractant, and inhibition of the CXCL2 receptor attenuated neutrophil infiltration and tissue damage in the inflamed pancreas. A significant role of CXCL4 was confirmed in an alternate model of AP induced by L-arginine challenge. Moreover, patients with AP had significantly increased plasma levels of CXCL4 compared with healthy controls. These findings' results suggest that platelet-derived CXCL4 is a potent stimulator of neutrophil accumulation in AP and that this is mediated via generation of CXCL2 in the inflamed pancreas. We conclude that CXCL4 plays an important role in pancreatic inflammation and that targeting CXCL4 might be a useful way to ameliorate tissue damage in AP. PMID- 27183220 TI - Silver-functionalized g-C3N4 nanohybrids as signal-transduction tags for electrochemical immunoassay of human carbohydrate antigen 19-9. AB - A simple and feasible electrochemical immunosensing platform was developed for highly efficient screening of a disease-related protein (human carbohydrate antigen 19-9, CA 19-9 used in this case) using silver-functionalized g-C3N4 nanosheets (Ag/g-C3N4) as signal-transduction tags. Initially, Ag/g-C3N4 nanohybrids were synthesized by combining thermal polymerization of the melamine precursor with the photo-assisted reduction method. Thereafter, the as synthesized Ag/g-C3N4 nanohybrids were utilized for the labeling of the anti-CA 19-9 detection antibody by using a typical carbodiimide coupling method. The assay was carried out on a capture antibody-modified glassy carbon electrode in a sandwich-type detection mode. The detectable signal mainly derived from the voltammetric characteristics of the immobilized nanosilver particles on the g C3N4 nanosheets within the applied potentials. Under the optimal conditions, the voltammetric peak currents increased with the increasing amount of target CA 19 9, and exhibited a wide linear range from 5.0 mU mL(-1) to 50 U mL(-1) with a detection limit of 1.2 mU mL(-1). Our strategy also displayed good reproducibility, precision and specificity. The results of the analysis of clinical serum specimens were in good accordance with the results obtained by an enzyme-linked immunosorbent assay (ELISA) method. The newly developed immunosensing system is promising for enzyme-free and cost-effective analysis of low-abundance proteins. PMID- 27183221 TI - Physician Payments from Industry Are Associated with Greater Medicare Part D Prescribing Costs. AB - BACKGROUND: The U.S. Physician Payments Sunshine Act mandates the reporting of payments or items of value received by physicians from drug, medical device, and biological agent manufacturers. The impact of these payments on physician prescribing has not been examined at large scale. METHODS: We linked public Medicare Part D prescribing data and Sunshine Act data for 2013. Physician payments were examined descriptively within specialties, and then for association with prescribing costs and patterns using regression models. Models were adjusted for potential physician-level confounding features, including sex, geographic region, and practice size. RESULTS: Among 725,169 individuals with Medicare prescribing data, 341,644 had documented payments in the OPP data (47.1%). Among all physicians receiving funds, mean payment was $1750 (SD $28336); median was $138 (IQR $48-$394). Across the 12 specialties examined, a dose-response relationship was observed in which greater payments were associated with greater prescribing costs per patient. In adjusted regression models, being in the top quintile of payment receipt was associated with incremental prescribing cost per patient ranging from $27 (general surgery) to $2931 (neurology). Similar associations were observed with proportion of branded prescriptions written. CONCLUSIONS: While distribution and amount of payments differed widely across medical specialties, for each of the 12 specialties examined the receipt of payments was associated with greater prescribing costs per patient, and greater proportion of branded medication prescribing. We cannot infer a causal relationship, but interventions aimed at those physicians receiving the most payments may present an opportunity to address prescribing costs in the US. PMID- 27183217 TI - Impact of pre-adapted HIV transmission. AB - Human leukocyte antigen class I (HLA)-restricted CD8(+) T lymphocyte (CTL) responses are crucial to HIV-1 control. Although HIV can evade these responses, the longer-term impact of viral escape mutants remains unclear, as these variants can also reduce intrinsic viral fitness. To address this, we here developed a metric to determine the degree of HIV adaptation to an HLA profile. We demonstrate that transmission of viruses that are pre-adapted to the HLA molecules expressed in the recipient is associated with impaired immunogenicity, elevated viral load and accelerated CD4(+) T cell decline. Furthermore, the extent of pre-adaptation among circulating viruses explains much of the variation in outcomes attributed to the expression of certain HLA alleles. Thus, viral pre adaptation exploits 'holes' in the immune response. Accounting for these holes may be key for vaccine strategies seeking to elicit functional responses from viral variants, and to HIV cure strategies that require broad CTL responses to achieve successful eradication of HIV reservoirs. PMID- 27183222 TI - SB-224289 Antagonizes the Antifungal Mechanism of the Marine Depsipeptide Papuamide A. AB - In order to expand the repertoire of antifungal compounds a novel, high throughput phenotypic drug screen targeting fungal phosphatidylserine (PS) synthase (Cho1p) was developed based on antagonism of the toxin papuamide A (Pap A). Pap-A is a cyclic depsipeptide that binds to PS in the membrane of wild-type Candida albicans, and permeabilizes its plasma membrane, ultimately causing cell death. Organisms with a homozygous deletion of the CHO1 gene (cho1DeltaDelta) do not produce PS and are able to survive in the presence of Pap-A. Using this phenotype (i.e. resistance to Pap-A) as an indicator of Cho1p inhibition, we screened over 5,600 small molecules for Pap-A resistance and identified SB-224289 as a positive hit. SB-224289, previously reported as a selective human 5-HT1B receptor antagonist, also confers resistance to the similar toxin theopapuamide (TPap-A), but not to other cytotoxic depsipeptides tested. Structurally similar molecules and truncated variants of SB-224289 do not confer resistance to Pap-A, suggesting that the toxin-blocking ability of SB-224289 is very specific. Further biochemical characterization revealed that SB-224289 does not inhibit Cho1p, indicating that Pap-A resistance is conferred by another undetermined mechanism. Although the mode of resistance is unclear, interaction between SB-224289 and Pap A or TPap-A suggests this screening assay could be adapted for discovering other compounds which could antagonize the effects of other environmentally- or medically-relevant depsipeptide toxins. PMID- 27183224 TI - Incorporation of Socio-Economic Features' Ranking in Multicriteria Analysis Based on Ecosystem Services for Marine Protected Area Planning. AB - Developed decades ago for spatial choice problems related to zoning in the urban planning field, multicriteria analysis (MCA) has more recently been applied to environmental conflicts and presented in several documented cases for the creation of protected area management plans. Its application is considered here for the development of zoning as part of a proposed marine protected area management plan. The case study incorporates specially-explicit conservation features while considering stakeholder preferences, expert opinion and characteristics of data quality. It involves the weighting of criteria using a modified analytical hierarchy process. Experts ranked physical attributes which include socio-economically valued physical features. The parameters used for the ranking of (physical) attributes important for socio-economic reasons are derived from the field of ecosystem services assessment. Inclusion of these feature values results in protection that emphasizes those areas closest to shore, most likely because of accessibility and familiarity parameters and because of data biases. Therefore, other spatial conservation prioritization methods should be considered to supplement the MCA and efforts should be made to improve data about ecosystem service values farther from shore. Otherwise, the MCA method allows incorporation of expert and stakeholder preferences and ecosystem services values while maintaining the advantages of simplicity and clarity. PMID- 27183223 TI - Improved Species-Specific Lysine Acetylation Site Prediction Based on a Large Variety of Features Set. AB - Lysine acetylation is a major post-translational modification. It plays a vital role in numerous essential biological processes, such as gene expression and metabolism, and is related to some human diseases. To fully understand the regulatory mechanism of acetylation, identification of acetylation sites is first and most important. However, experimental identification of protein acetylation sites is often time consuming and expensive. Therefore, the alternative computational methods are necessary. Here, we developed a novel tool, KA predictor, to predict species-specific lysine acetylation sites based on support vector machine (SVM) classifier. We incorporated different types of features and employed an efficient feature selection on each type to form the final optimal feature set for model learning. And our predictor was highly competitive for the majority of species when compared with other methods. Feature contribution analysis indicated that HSE features, which were firstly introduced for lysine acetylation prediction, significantly improved the predictive performance. Particularly, we constructed a high-accurate structure dataset of H.sapiens from PDB to analyze the structural properties around lysine acetylation sites. Our datasets and a user-friendly local tool of KA-predictor can be freely available at http://sourceforge.net/p/ka-predictor. PMID- 27183226 TI - Two-dimensional cyanates: stabilization through hydrogenation. AB - According to first-principles calculations, it should be possible to grow two dimensional (2D) forms of copper thio-cyanate (CuSCN) and copper seleno-cyanate (CuSeCN) since their energies are only marginally higher than those of their most stable three-dimensional (3D) wurtzite structures. Here we show using the same theoretical approach that chemisorption reactions of hydrogen molecules with the above-mentioned 2D CuSCN and CuSeCN systems enhance their stability as they decrease the energy difference with respect to the corresponding hydrogenated forms of the wurtzite crystals. Hydrogenation causes a sizeable decrease in the energy band gap by 0.56 eV and 0.65 eV for hydrogenated 2D-CuSCN (CuSCNH2) and 2D CuSeCN (CuSeCNH2), respectively. Finally, we describe the stability of hydrogen vacancies in CuSCNH2 and CuSeCNH2 and show that the presence of isolated single H vacancies or di-vacancies does not affect significantly the electronic properties of the host systems close to the valence and conduction band edges. PMID- 27183225 TI - Cyclophilin D Knock-Out Mice Show Enhanced Resistance to Osteoporosis and to Metabolic Changes Observed in Aging Bone. AB - Pathogenic factors associated with aging, such as oxidative stress and hormone depletion converge on mitochondria and impair their function via opening of the mitochondrial permeability transition pore (MPTP). The MPTP is a large non selective pore regulated by cyclophilin D (CypD) that disrupts mitochondrial membrane integrity. MPTP involvement has been firmly established in degenerative processes in heart, brain, and muscle. Bone has high energy demands and is therefore expected to be highly sensitive to mitochondrial dysfunction. Despite this, the role of mitochondria and the MPTP in bone maintenance and bone pathology has not been elucidated. Our goal was to determine whether mitochondria are impaired in aging bone and to see if protecting mitochondria from MPTP opening via CypD deletion protects against bone loss. We found that bone mass, strength, and formation progressively decline over the course of 18 months in C57BL/6J mice. Using metabolomics and electron microscopy, we determined that oxidative metabolism is impaired in aging bone leading to a glycolytic shift, imbalance in nucleotides, and decreased NAD+/NADH ratio. Mitochondria in osteocytes appear swollen which is a major marker of MPTP opening. CypD deletion by CypD knockout mouse model (CypD KO) protects against bone loss in 13- and 18 month-old mice and prevents decline in bone formation and mitochondrial changes observed in wild type C57BL/6J mice. Together, these data demonstrate that mitochondria are impaired in aging bone and that CypD deletion protects against this impairment to prevent bone loss. This implicates CypD-regulated MPTP and mitochondrial dysfunction in the impairment of bone cells and in aging-related bone loss. Our findings suggest mitochondrial metabolism as a new target for bone therapeutics and inhibition of CypD as a novel strategy against bone loss. PMID- 27183227 TI - At the Crossroads: Does the Configuration of Roadside Vegetation Affect Woodland Bird Communities in Rural Landscapes? AB - In agricultural regions worldwide, linear networks of vegetation such as hedges, fencerows and live fences provide habitat for plant and animal species in heavily modified landscapes. In Australia, networks of remnant native vegetation along roadsides are a distinctive feature of many rural landscapes. Here, we investigated the richness and composition of woodland-dependent bird communities in networks of eucalypt woodland vegetation along roadsides, in an agricultural region in which >80% of native woodland and forest vegetation has been cleared. We stratified sites in a) cross sections and b) linear strips of roadside vegetation, to test the influence on woodland birds of site location and configuration in the linear network (the 'intersection effect'). We also examined the influence of tree size at the site, the amount of wooded vegetation surrounding the site, and the abundance of an aggressive native species, the noisy miner Manorina melanocephala. Birds were surveyed at 26 pairs of sites (cross section or linear strip) on four occasions. A total of 66 species was recorded, including 35 woodland species. The richness of woodland bird species was influenced by site configuration, with more species present at cross sections, particularly those with larger trees (>30 cm diameter). However, the strongest influence on species richness was the relative abundance of the noisy miner. The richness of woodland birds at sites where noisy miners were abundant was ~20% of that where miners were absent. These results recognise the value of networks of roadside vegetation as habitat for woodland birds in depleted agricultural landscapes; but highlight that this value is not realised for much of this vast vegetation network because of the dominance of the noisy miner. Nevertheless, roadside vegetation is particularly important where the configuration of networks create nodes that facilitate movement. Globally, the protection, conservation and restoration of such linear networks has an important influence on the persistence of biota within human-dominated landscapes. PMID- 27183229 TI - Penicillium salamii strain ITEM 15302: A new promising fungal starter for salami production. AB - Traditional sausages are often considered of superior quality to sausages inoculated with commercial starter cultures and this is partially due to the action of the typical house microflora. Penicillium nalgiovense is the species commonly used as starter culture for dry-cured meat production. Recently a new species, Penicillium salamii, was described as typical colonizer during salami seasoning. In order to understand its contribution to the seasoning process, two different experiments on curing of fresh pork sausages were conducted using P. salamii ITEM 15302 in comparison with P. nalgiovense ITEM 15292 at small and industrial scale, and the dry-cured sausages were subjected to sensory analyses. Additionally, proteolytic and lipolytic in vitro assays were performed on both strains. P. salamii ITEM 15302 proved to be a fast growing mould on dry-cured sausage casings, well adapted to the seasoning process, with high lipolytic and proteolytic enzymatic activity that confers typical sensory characteristics to meat products. Therefore, P. salamii ITEM 15302 was shown to be a good candidate as new starter for meat industry. PMID- 27183228 TI - Plasma Acylcarnitines and Amino Acid Levels As an Early Complex Biomarker of Propensity to High-Fat Diet-Induced Obesity in Mice. AB - Obesity is associated with insulin resistance and impaired glucose tolerance, which represent characteristic features of the metabolic syndrome. Development of obesity is also linked to changes in fatty acid and amino acid metabolism observed in animal models of obesity as well as in humans. The aim of this study was to explore whether plasma metabolome, namely the levels of various acylcarnitines and amino acids, could serve as a biomarker of propensity to obesity and impaired glucose metabolism. Taking advantage of a high phenotypic variation in diet-induced obesity in C57BL/6J mice, 12-week-old male and female mice (n = 155) were fed a high-fat diet (lipids ~32 wt%) for a period of 10 weeks, while body weight gain (BWG) and changes in insulin sensitivity (DeltaHOMA IR) were assessed. Plasma samples were collected before (week 4) and after (week 22) high-fat feeding. Both univariate and multivariate statistical analyses were then used to examine the relationships between plasma metabolome and selected phenotypes including BWG and DeltaHOMA-IR. Partial least squares-discrimination analysis was able to distinguish between animals selected either for their low or high BWG (or DeltaHOMA-IR) in male but not female mice. Among the metabolites that differentiated male mice with low and high BWG, and which also belonged to the major discriminating metabolites when analyzed in plasma collected before and after high-fat feeding, were amino acids Tyr and Orn, as well as acylcarnitines C16-DC and C18:1-OH. In general, the separation of groups selected for their low or high DeltaHOMA-IR was less evident and the outcomes of a corresponding multivariate analysis were much weaker than in case of BWG. Thus, our results document that plasma acylcarnitines and amino acids could serve as a gender specific complex biomarker of propensity to obesity, however with a limited predictive value in case of the associated impairment of insulin sensitivity. PMID- 27183230 TI - Evaluation of the risk of fungal spoilage when substituting sucrose with commercial purified Stevia glycosides in sweetened bakery products. AB - The objectives of this study were to compare the effect of different Stevia-based sugar substitutes (S1-S3), sucrose alone and a mixture of sucrose+S1 on: (a) humectant properties, (b) relative colonisation rates of sponge cake slices at 0.90 aw by strains of Aspergillus flavus, Eurotium amstelodami, Fusarium graminearum and Penicillium verrucosum at 20 and 25 degrees C and (c) shelf-life periods in days prior to visible growth. Results showed that sucrose, S1 commercial sugar substitute and the mixture of sucrose+S1 in water solutions were able to reach water activity levels similar to those of glycerol and glucose mixtures. The S2 and S3 commercial sugar substitutes were unable to reduce aw levels significantly. At 25 degrees C, colonisation of sponge cake slices by E. amstelodami, A. flavus and P. verrucosum occurred in all the treatments. Growth of F. graminearum only occurred on sponge cake slices containing S2 and S3 Stevia based products at both temperatures. The best control of growth (30days) was achieved in cake slices modified with sucrose or S1 Stevia treatments inoculated with A. flavus and in the sucrose treatment for E. amstelodami at 20 degrees C. F. graminearum growth was completely inhibited when sucrose alone, S1 or sucrose+S1 treatments were used at both temperatures. This study suggests that, as part of a hurdle technology approach, replacing sucrose with low calorie sugar substitutes based on Stevia glycosides needs to be done with care. This is because different products may have variable humectant properties and bulking agents which may shorten the potential shelf-life of intermediate moisture bakery products. PMID- 27183231 TI - Who Should Be Targeted for the Prevention of Birth Defects? A Latent Class Analysis Based on a Large, Population-Based, Cross-Sectional Study in Shaanxi Province, Western China. AB - BACKGROUND: The wide range and complex combinations of factors that cause birth defects impede the development of primary prevention strategies targeted at high risk subpopulations. METHODS: Latent class analysis (LCA) was conducted to identify mutually exclusive profiles of factors associated with birth defects among women between 15 and 49 years of age using data from a large, population based, cross-sectional study conducted in Shaanxi Province, western China, between August and October, 2013. The odds ratios (ORs) and 95% confidence intervals (CIs) of associated factors and the latent profiles of indicators of birth defects and congenital heart defects were computed using a logistic regression model. RESULTS: Five discrete subpopulations of participants were identified as follows: No folic acid supplementation in the periconceptional period (reference class, 21.37%); low maternal education level + unhealthy lifestyle (class 2, 39.75%); low maternal education level + unhealthy lifestyle + disease (class 3, 23.71%); unhealthy maternal lifestyle + advanced age (class 4, 4.71%); and multi-risk factor exposure (class 5, 10.45%). Compared with the reference subgroup, the other subgroups consistently had a significantly increased risk of birth defects (ORs and 95% CIs: class 2, 1.75 and 1.21-2.54; class 3, 3.13 and 2.17-4.52; class 4, 5.02 and 3.20-7.88; and class 5, 12.25 and 8.61-17.42, respectively). For congenital heart defects, the ORs and 95% CIs were all higher, and the magnitude of OR differences ranged from 1.59 to 16.15. CONCLUSIONS: A comprehensive intervention strategy targeting maternal exposure to multiple risk factors is expected to show the strongest results in preventing birth defects. PMID- 27183233 TI - Near-Infrared Spectroscopy to Predict the Course of Necrotizing Enterocolitis. AB - OBJECTIVES: To investigate whether cerebral, liver, and infraumbilical regional tissue oxygen saturation (rSO2) and fractional tissue oxygen extraction (FTOE) could be used to diagnose necrotizing enterocolitis (NEC) and complicated NEC (Bell's stage 3B or death) during its early stages. METHODS: A prospective observational cohort study of preterm infants with suspected or diagnosed NEC. We compared the mean eight-hour cerebral, liver, and infraumbilical rSO2 and FTOE values of infants with no NEC and definite NEC and of infants with uncomplicated and complicated NEC in the first forty-eight hours after onset of symptoms, suspicious for NEC. Furthermore, we determined cut-off values by generating receiver operating characteristics curves in case of significant differences in the first eight-hour mean values of rSO2 between infants with no NEC and definite NEC and between infants with uncomplicated and complicated NEC. RESULTS: We included 33 patients: 13 no NEC, 10 with uncomplicated NEC, and 10 with complicated NEC. We found no significant differences in the first twenty-four hours after onset of symptoms in rSO2 and FTOE between infants with no NEC and definite NEC. In preterm infants with complicated NEC, we observed significantly lower cerebral, liver, and infraumbilical rSO2 and higher FTOE within twenty-four hours after onset of symptoms compared with infants with uncomplicated NEC. A continuous cerebral rSO2 <= 71% and liver rSO2 <= 59% in the first eight hours after onset of symptoms predicted the onset of complicated NEC with a sensitivity of 1.0 and specificity of 0.8, and a sensitivity of 1.0 and specificity of 1.0, respectively. CONCLUSIONS: By measuring the cerebral and splanchnic oxygenation it is possible to differentiate complicated NEC from uncomplicated NEC. In our sample, NIRS monitoring did not proof useful for distinguishing between definite NEC and no NEC in preterm infants with clinical signs suspicious of NEC. PMID- 27183232 TI - Changes in Familiarity with and Willingness to Take Preexposure Prophylaxis in a Longitudinal Study of Highly Sexually Active Gay and Bisexual Men. AB - PURPOSE: For gay and bisexual men (GBM), research suggests that familiarity with preexposure prophylaxis (PrEP) has been increasing since being approved by the United States Food and Drug Administration in 2012. However, it is less clear how willingness to start using PrEP has changed over time. Likewise, some have expressed concerns regarding the potential for risk compensation (i.e., reduced condom use) were one to start PrEP; however, again, it is unclear how risk compensation may have changed over time. METHODS: We conducted baseline and 12 month assessments with 158 highly sexually active HIV-negative GBM in New York City who were assessed between 2011 and 2014. We examined change over time both between participants (based on when they entered the study), as well as within each participant (over the 12 months of his involvement). RESULTS: Familiarity with PrEP increased over time (both between and within participants); however, willingness to take PrEP did not change (neither between nor within participants). Few men believed taking PrEP would cause their condomless anal sex (CAS) to increase and this did not change over time. However, a majority believed PrEP would increase temptation for CAS, and this did not change over time within participants. Sexual compulsivity symptomology was associated with higher willingness to take PrEP and perceiving that PrEP would increase one's temptations for CAS. Furthermore, recent CAS was associated with greater willingness to take PrEP, a perception that PrEP would increase one's likelihood to engage in CAS, and a perception that being on PrEP would increase one's temptation for CAS. CONCLUSIONS: Participants became more familiar with PrEP over time; however, willingness to start PrEP did not change, and this may serve as an opportunity for providers to discuss PrEP with their patients. Men who engaged in CAS were interested in PrEP and preexisting patterns of sexual behavior may be the primary determinant of CAS while on PrEP. PMID- 27183234 TI - Cometabolic degradation of lincomycin in a Sequencing Batch Biofilm Reactor (SBBR) and its microbial community. AB - Cometabolism technology was employed to degrade lincomycin wastewater in Sequencing Batch Biofilm Reactor (SBBR). In contrast with the control group, the average removal rate of lincomycin increased by 56.0% and Total Organic Carbon (TOC) increased by 52.5% in the cometabolic system with glucose as growth substrate. Under the same condition, Oxidation-Reduction Potential (ORP) was 85.1+/-7.3mV in cometabolic system and 198.2+/-8.4mV in the control group, indicating that glucose changed the bulk ORP and created an appropriate growing environment for function bacteria. Functional groups of lincomycin were effectively degraded in cometabolic system proved by FTIR and GC-MS. Meanwhile, results of DGGE and 16S rDNA showed great difference in dominant populations between cometabolic system and the control group. In cometabolic system, Roseovarius (3.35%), Thiothrix (2.74%), Halomonas (2.49%), Ignavibacterium (2.02%), and TM7_genus_incertae_sedis (1.93%) were verified as dominant populations at genus level. Cometabolism may be synergistically caused by different functional dominant bacteria. PMID- 27183235 TI - Acetate favors more phosphorus accumulation into aerobic granular sludge than propionate during the treatment of synthetic fermentation liquor. AB - Anaerobic digestion (AD) is an efficient biotechnology widely applied for energy and resource recovery from organic waste and wastewater treatment. The effluent from AD or fermentation liquor containing organic substances like volatile fatty acids (VFAs) and mineral nutrients (such as N and P), however, will trigger serious environmental issues if not properly dealt with. In this study two identical sequencing batch reactors (SBRs), namely Ra and Rp were used to cultivate aerobic granules for P recovery from synthetic fermentation liquor, respectively using acetate and propionate as additional carbon source. Larger and more stable granules were achieved in Ra with higher P removal capability (9.4mgP/g-VSS.d) and higher anaerobic P release (6.9mgP/g-VSS.h). In addition to much higher P content (78mgP/g-SS), bioavailable P in Ra-granules increased to 45mgP/g-SS, approximately 2-times those of seed sludge and Rp-granules. Microbial community analysis indicated that more GAOs were accumulated in Rp-granules. PMID- 27183236 TI - Optimization of Extracellular Polymeric Substances production using Azotobacter beijreinckii and Bacillus subtilis and its application in chromium (VI) removal. AB - Extracellular Polymeric Substances (EPS) of microbial origin are complex biopolymers and vary greatly in their chemical composition. They have a great potential in chelation of metal ions. In this work, the effect of growth phase, temperature and pH on production of EPS by two bacteria Azotobacter beijreinckii and Bacillus subtilis have been studied. Extracted EPS was used to remove Cr(VI) from aqueous system. A. beijreinckii produced maximum EPS after 24h at pH 7 and temperature 30 degrees C while B. subtilis produced maximum EPS after 96h at pH 7 and temperature 37 degrees C. For an initial concentration of 10ppm, 26% and 48% Cr(VI) removal was recorded for EPS derived from A. beijreinckii and B. subtilis respectively. The presence of functional groups on EPS and their interaction with Cr(VI) was confirmed using Fourier-transform infrared (FTIR) spectra analysis. In both the bacteria, carboxyl and phosphate groups show involvement in metal binding. PMID- 27183237 TI - Hydrodynamic cavitation-assisted alkaline pretreatment as a new approach for sugarcane bagasse biorefineries. AB - Hydrodynamic cavitation (HC) was employed in order to improve the efficiency of alkaline pretreatment of sugarcane bagasse (SCB). Response surface methodology (RSM) was used to optimize pretreatment parameters: NaOH concentration (0.1 0.5M), solid/liquid ratio (S/L, 3-10%) and HC time (15-45min), in terms of glucan content, lignin removal and enzymatic digestibility. Under an optimal HC condition (0.48M of NaOH, 4.27% of S/L ratio and 44.48min), 52.1% of glucan content, 60.4% of lignin removal and 97.2% of enzymatic digestibility were achieved. Moreover, enzymatic hydrolysis of the pretreated SCB resulted in a yield 82% and 30% higher than the untreated and alkaline-treated controls, respectively. HC was found to be a potent and promising approach to pretreat lignocellulosic biomass. PMID- 27183238 TI - Effect of torrefaction pretreatment and catalytic pyrolysis on the pyrolysis poly generation of pine wood. AB - Torrefaction of pine wood was performed in a tube furnace at three temperatures (220, 250, and 280 degrees C) for 30min. Then catalytic pyrolysis of raw and torrefied pine wood was performed using HZSM-5 catalyst in a fixed-bed pyrolysis reactor at 550 degrees C for 15min. Torrefaction pretreatment and catalytic pyrolysis have an very important effect on the yield, property, and energy distribution of pyrolysis products. The results showed that the yield of biochar rapidly increased, while that of bio-oil decreased with increasing torrefaction temperature. The oxy-compound content of bio-oil, such as acids and aldehydes, sharply decreased. However, the aromatic hydrocarbon content not only increased but also further promoted by HZSM-5 catalyst. With highest mass yields and energy yields, biochar was also the very important product of pyrolysis. The oxygen content in biomass was mainly removed in the form of CO2 and H2O, leading to increasing CO2 content in non-condensable gas. PMID- 27183239 TI - Levetiracetam inhibits oligomeric Abeta-induced glutamate release from human astrocytes. AB - A recently identified mechanism for oligomeric Abeta-induced glutamate release from astrocytes involves intracellular Ca elevation, potentially by Ca-dependent vesicular release. Evidence suggests that levetiracetam (LEV; Keppra), an antiepileptic drug, can improve cognitive performance in both humans with mild cognitive impairment and animal models of Alzheimer disease. Because LEV acts by modulating neurotransmitter release from neurons by interaction with synaptic vesicles, we tested the effect of LEV on Abeta-induced astrocytic release of glutamate. We used a fluorescence resonance energy transfer-based glutamate sensor (termed SuperGluSnFR), whose structure is based on the ligand-binding site of glutamate receptors, to monitor glutamate release from primary cultures of human astrocytes exposed to oligomeric amyloid-beta peptide 1-42 (Abeta42). We found that LEV (10 uM) inhibited oligomeric Abeta-induced astrocytic glutamate release. In addition, we show that this Abeta-induced glutamate release from astrocytes is sensitive to tetanus neurotoxin, an inhibitor of the vesicle release machinery. Taken together, our evidence suggests that LEV inhibits Abeta induced vesicular glutamate release from astrocytes and thus may underlie, at least in part, the ability of LEV to reduce hyperexcitability in Alzheimer disease. PMID- 27183240 TI - Incidence of Soft-Tissue Injuries in Patients with Posterolateral Tibial Plateau Fractures: A Retrospective Review from 2009 to 2014. AB - Objective The goal of this study was to determine the incidence of soft-tissue injuries in patients with posterolateral tibial plateau fractures. Methods The data of 265 patients who had sustained posterolateral tibial plateau fractures between May 2009 and Aug 2014 were retrospectively reviewed using a picture archiving and communication system. Fractures were classified according to the Schatzker, AO/OTA, and quadrant classification systems. Soft-tissue injuries, including anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), lateral collateral ligament (LCL), medial collateral ligament (MCL), lateral meniscus, and medial meniscus injuries, were assessed using magnetic resonance imaging (MRI) data. Results The overall incidence of ACL and PCL tears was 80 and 36%, respectively. Nine (36%) patients sustained ACL footprint avulsions and three (12%) had complete ACL tears. A total of 19 (76%) patients had LCL injuries, and 15 (64%) had MCL injuries. The incidence of lateral meniscus tears was 48%, while that of medial meniscus tears was 4%. Conclusion Posterolateral tibial plateau fractures were associated with a high incidence of soft-tissue injuries, especially ACL footprint avulsions and lateral meniscus tears. The preoperative MRI examination was important for surgeons to decide whether the ligament and meniscal injuries should be treated simultaneously with the repair of the bone fractures. PMID- 27183241 TI - microManaging glucose and lipid metabolism in skeletal muscle: Role of microRNAs. AB - MicroRNAs have been described as important regulators of skeletal muscle differentiation and development, but the role of microRNAs in glucose and lipid metabolism is less well established. Here we review the microRNAs involved in insulin resistance and glucose metabolism, as well as microRNAs regulating lipid metabolism and mitochondrial functions in skeletal muscle, with an emphasis on metabolic disorders such as type 2 diabetes and the adaptive response to exercise training. Finally, we raise some methodological considerations for studying microRNAs, as well as challenges investigators may face when elucidating the direct role of microRNAs in the regulation of glucose and lipid metabolism in skeletal muscle. This article is part of a Special Issue entitled: MicroRNAs and lipid/energy metabolism and related diseases edited by Carlos Fernandez-Hernando and Yajaira Suarez. PMID- 27183242 TI - Tailoring Supramolecular Nanofibers for Air Filtration Applications. AB - The demand of new materials and processes for nanofiber fabrication to enhance the performance of air filters is steadily increasing. Typical approaches to obtain nanofibers are based on top-down processes such as melt blowing, centrifugal spinning, and electrospinning of polymer materials. However, fabrication of polymer nanofibers is limited with respect to either a sufficiently high throughput or the smallest achievable fiber diameter. This study reports comprehensively on a fast and simple bottom-up process to prepare supramolecular nanofibers in situ inside viscose/polyester microfiber nonwovens. Here, selected small molecules of the materials class of 1,3,5-benzenetrisamides are employed. The microfiber-nanofiber composites exhibit a homogeneous nanofiber distribution and morphology throughout the entire nonwoven scaffold. Small changes in molecular structure and processing solvent have a strong influence on the final nanofiber diameter and diameter distribution and, consequently, on the filtration performance. Choosing proper processing conditions, microfiber nanofiber composites with surprisingly high filtration efficiencies of particulate matter are obtained. In addition, the microfiber-nanofiber composite integrity at elevated temperatures was determined and revealed that the morphology of supramolecular nanofibers is maintained compared to that of the utilized polymer nonwoven. PMID- 27183243 TI - Aid in Dying and Palliative Sedation. PMID- 27183244 TI - Comparison between objective measures and parental behavioral rating scales of memory and attention in pediatric endocrinology patients. AB - : Behavioral rating scales represent one potential method for screening of cognitive functioning in routine clinical care. It is not yet known if objective performance based measures and behavioral rating scales of cognitive functioning completed by parents yield similar information in pediatric endocrinology patients. The purpose of the present study was to evaluate the associations between performance-based measures and behavioral rating scales of memory and attention/concentration completed by parents of pediatric patients with Type 1 Diabetes or obesity. The sample consisted of 73 pediatric patients with Type 1 Diabetes or obesity (BMI > 95th percentile) ages 6-16 years (mean age = 12.29 years) referred to an outpatient pediatric endocrinology clinic. Youth were administered the Wide Range Assessment of Memory and Learning (WRAML-2). Parents completed the Child Behavior Checklist (CBCL) and the PedsQL Cognitive Functioning Scale. Pearson's Product Moment Correlations were examined among the performance-based measures and behavioral rating scales. RESULTS: All intercorrelations between the performance-based measures and behavioral rating scales completed by parents were in the small range. The only statistically significant (P < 0.05) and approaching medium correlation was between the PedsQL Cognitive Functioning Scale and WRAML-2 Verbal Memory Index (r = 0.28). On behavioral rating scales and performance-based measures of visual memory and attention/concentration, our sample exhibited greater difficulties than healthy youth from previously published data (P < 0.05). One possible explanation for our findings is that behavioral rating scales of attention/concentration and memory completed by parents measure different aspects of cognitive functioning than performance based measures in pediatric patients with Type 1 Diabetes or obesity. PMID- 27183245 TI - Differences in physical status, mental state and online behavior of people in pro anorexia web communities. AB - BACKGROUND: There is a debate about the effects of pro-anorexia (colloquially referred to as pro-ana) websites. Research suggests that the effect of these websites is not straightforward. Indeed, the actual function of these sites is disputed, with studies indicating both negative and positive effects. AIM: This is the first study which systematically examined the differences between pro anorexia web communities in four main aspects: web language used (posts); web interests/search behaviors (queries); users' self-reported weight status and weight goals; and associated self-reported mood/pathology. METHODS: We collected three primary sources of data, including messages posed on three pro-ana websites, a survey completed by over 1000 participants of a pro-ana website, and the searches made on the Bing search engine of pro-anorexia users. These data were analyzed for content, reported demographics and pathology, and behavior over time. RESULTS: Although members of the main pro-ana website investigated appear to be depressed, with high rates of self-harm and suicide attempts, users are significantly more interested in treatment, have wishes of procreation and reported the highest goal weights among the investigated sites. In contrast, users of other pro-ana websites investigated, are more interested in morbid themes including depression, self-harm and suicide. The percentage of severely malnourished website users, in general, appears to be small (20%). CONCLUSIONS: Our results indicate that a new strategy is required to facilitate the communication between mental health specialists and pro-ana web users, recognizing the differences in harm associated with different websites. PMID- 27183246 TI - Fractionated ablative carbon dioxide laser treatment of steatocystoma multiplex. AB - Steatocystoma multiplex is a well-recognized condition in which subjects develop dermal cysts generally inherited in an autosomal dominant fashion, though these can occur sporadically. This case report describes the successful treatment of a 51-year-old woman with steatocystomata limited to the face, who after two treatments with a fractionated ablative carbon dioxide laser remained free of cysts for three years. We conclude that this treatment should be considered as an efficient and effective treatment option for patients with steatocystoma multiplex. PMID- 27183247 TI - Capturing Guest Dynamics in Metal-Organic Framework CPO-27-M (M = Mg, Zn) by (2)H Solid-State NMR Spectroscopy. AB - Metal-organic frameworks (MOFs) are promising porous materials for gas separation and storage as well as sensing. In particular, a series of isostructural MOFs with coordinately unsaturated metal centers, namely, CPO-27-M or M-MOF-74 (M = Mg, Zn, Mn, Fe, Ni, Co, Cu), have shown exceptional adsorption capacity and selectivity compared to those of classical MOFs that contain only fully coordinated metal sites. Although it is widely accepted that the interaction between guest molecules and exposed metal centers is responsible for good selectivity and large maximum uptake, the investigation of such guest-metal interaction is very challenging because adsorbed molecules are usually disordered in the pores and undergo rapid thermal motions. (2)H solid-state NMR (SSNMR) spectroscopy is one of the most extensively used techniques for capturing guest dynamics in porous materials. In this work, variable-temperature (2)H wide-line SSNMR experiments were performed on CPO-27-M (M = Mg, Zn) loaded with four prototypical guest molecules: D2O, CD3CN, acetone-d6, and C6D6. The results indicate that different guest molecules possess distinct dynamic behaviors inside the channel of CPO-27-M. For a given guest molecule, its dynamic behavior also depends on the nature of the metal centers. The binding strength of guest molecules is discussed on the basis of the (2)H SSNMR data. PMID- 27183248 TI - Ultrafast dynamics of ligand and substrate interaction in endothelial nitric oxide synthase under Soret excitation. AB - Ultrafast transient absorption spectroscopy of endothelial NOS oxygenase domain (eNOS-oxy) was performed to study dynamics of ligand or substrate interaction under Soret band excitation. Photo-excitation dissociates imidazole ligand in <300fs, then followed by vibrational cooling and recombination within 2ps. Such impulsive bond breaking and late rebinding generate proteinquakes, which relaxes in several tens of picoseconds. The photo excited dynamics of eNOS-oxy with L arginine substrate mainly occurs at the local site of heme, including ultrafast internal conversion within 400fs, vibrational cooling, charge transfer, and complete ground-state recovery within 1.4ps. The eNOS-oxy without additive is partially bound with water molecule, thus its photoexcited dynamics also shows ligand dissociation in <800fs. Then it followed by vibrational cooling coupled with charge transfer in 4.8ps, and recombination of ligand to distal side of heme in 12ps. PMID- 27183249 TI - Synthesis and characterization of a pH responsive folic acid functionalized polymeric drug delivery system. AB - We report the computational analysis, synthesis and characterization of folate functionalized poly(styrene-alt-maleic anhydride), PSMA for drug delivery purpose. The selection of the proper linker between the polymer and the folic acid group was performed before conducting the synthesis using Density Functional Theory (DFT). The computational results showed the bio-degradable linker 2, 4 diaminobutyric acid, DABA as a good candidate allowing flexibility of the folic acid group while maintaining the pH sensitivity of PSMA, used as a trigger for drug release. The synthesis was subsequently carried out in multi-step experimental procedures. The functionalized polymer was characterized using InfraRed spectroscopy, Nuclear Magnetic Resonance and Dynamic Light Scattering confirming both the chemical structure and the pH responsiveness of PSMA-DABA Folate polymers. This study provides an excellent example of how computational chemistry can be used in selection process for the functional materials and product characterization. The pH sensitive polymers are expected to be used in delivering anti-cancer drugs to solid tumors with overly expressed folic acid receptors. PMID- 27183250 TI - Idarucizumab for Dabigatran Reversal Guideline. PMID- 27183251 TI - Postgraduate Education in Quality Improvement Methods: Initial Results of the Fellows' Applied Quality Training (FAQT) Curriculum. AB - OBJECTIVE: Training in quality improvement (QI) is a pillar of the next accreditation system of the Accreditation Committee on Graduate Medical Education and a growing expectation of physicians for maintenance of certification. Despite this, many postgraduate medical trainees are not receiving training in QI methods. We created the Fellows Applied Quality Training (FAQT) curriculum for cardiology fellows using both didactic and applied components with the goal of increasing confidence to participate in future QI projects. METHODS AND RESULTS: Fellows completed didactic training from the Institute for Healthcare Improvement's Open School and then designed and completed a project to improve quality of care or patient safety. Self-assessments were completed by the fellows before, during, and after the first year of the curriculum. The primary outcome for our curriculum was the median score reported by the fellows regarding their self-confidence to complete QI activities. Self-assessments were completed by 23 fellows. The majority of fellows (15 of 23, 65.2%) reported no prior formal QI training. Median score on baseline self-assessment was 3.0 (range, 1.85-4), which was significantly increased to 3.27 (range, 2.23-4; P = 0.004) on the final assessment. The distribution of scores reported by the fellows indicates that 30% were slightly confident at conducting QI activities on their own, which was reduced to 5% after completing the FAQT curriculum. An interim assessment was conducted after the fellows completed didactic training only; median scores were not different from the baseline (mean, 3.0; P = 0.51). CONCLUSION: After completion of the FAQT, cardiology fellows reported higher self-confidence to complete QI activities. The increase in self-confidence seemed to be limited to the applied component of the curriculum, with no significant change after the didactic component. PMID- 27183252 TI - Short- and Long-Term Prognostic Utility of the HEART Score in Patients Evaluated in the Emergency Department for Possible Acute Coronary Syndrome. AB - INTRODUCTION: The HEART score is a risk-stratification tool that was developed and validated for patients evaluated for possible acute coronary syndrome (ACS) in the emergency department (ED). We sought to determine the short-term and long term prognostic utility of the HEART score. METHODS: A retrospective single center analysis of 947 patients evaluated for possible ACS in the ED in 1999 was conducted. Patients were followed for major adverse cardiac events (MACEs) at 30 days: death, acute myocardial infarction, or revascularization procedure. All cause mortality was assessed at 5 years. The HEART score was compared with the Thrombolysis in Myocardial Infarction (TIMI) score. RESULTS: At 30 days, 14% (135/947) of patients had an MACE: 48 deaths (5%), 84 acute myocardial infarctions (9%), and 48 (5%) revascularization procedures. The MACE rate in patients with HEART score <=3 was 0.6% (1/175) involving a revascularization procedure, 9.5% (53/557) in patients with HEART score between 4 and 6, and 38% (81/215) with HEART score >=7. The C-statistic for the HEART score was 0.82 and 0.68 for the TIMI score for predicting 30-day MACE (P < 0.05). Patients with HEART score <=3 had lower 5-year mortality rate compared with those with TIMI score of 0 (10.6% vs. 20.5%, P = 0.02). CONCLUSIONS: The HEART score is a valuable risk-stratification tool in predicting not only short-term MACE but also long-term mortality in patients evaluated for possible ACS in the ED. The HEART score had a superior prognostic value compared with the TIMI score. PMID- 27183253 TI - Chest Pain Risk Stratification: A Comparison of the 2-Hour Accelerated Diagnostic Protocol (ADAPT) and the HEART Pathway. AB - BACKGROUND: The 2-hour accelerated diagnostic protocol (ADAPT) and the history electrocardiogram age risk factors troponin (HEART) Pathway are decision aids designed to identify Emergency Department (ED) patients with chest pain who are safe for early discharge. Both have demonstrated high sensitivity (>99%) for major adverse cardiac events (MACE) at 30 days and early discharge rates >=20%. The objective of this study is to compare the sensitivity and early discharge rates of the ADAPT and HEART Pathway decision aids in a cohort of ED patients with acute chest pain. METHODS: A secondary analysis of participants enrolled and randomized to the HEART Pathway arm of the HEART pathway randomized controlled trial was conducted. Each patient was prospectively classified as low risk (suitable for early discharge) or high risk by ADAPT and the HEART Pathway. Sensitivity for MACE at 30 days and the number of patients identified as low-risk were calculated for each decision aid. Decision aid performance was compared using McNemar's test. RESULTS: MACE occurred in 8 of 141 (5.7%); there were no deaths, 7 patients had myocardial infarction, and 1 patient had coronary revascularization without myocardial infarction. ADAPT and the HEART pathway identified all patients with MACE as high risk; sensitivity for MACE of 100% [95% confidence interval (CI): 63-100%]. ADAPT identified 34 of 141 patients (24%; 95% CI: 17-32%) as low-risk, whereas the Heart pathway identified 66 of 141 patients (47%, 95% CI: 38-55%) as low risk (P < 0.001). CONCLUSIONS: Within a cohort of ED patients with acute chest pain, ADAPT and the HEART pathway had high sensitivity for MACE. The HEART pathway outperformed ADAPT by correctly identifying more patients as low risk and safe for early discharge. PMID- 27183254 TI - Prognostic Factors in Chest Pain Patients: A Quantitative Analysis of the HEART Score. AB - OBJECTIVES: Risk stratification for chest pain patients at the emergency department is recommended in several guidelines. The history, ECG, age, risk factors, and troponin (HEART) score is based on medical literature and expert opinion to estimate the risk of a major adverse cardiac event. We aimed to assess the predictive effects of the 5 HEART components and to compare performances of the original HEART score and a model based on regression analysis. METHODS: We analyzed prospectively collected data from 2388 patients, of whom 407 (17%) had a major adverse cardiac event within 6 weeks (acute myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, significant stenosis with conservative treatment and death due to any cause). RESULTS: Univariate regression analysis showed the same ordering of predictive effects as used in the HEART score. Based on multivariable logistic regression analysis, an adjusted score showed slightly better calibration and discrimination (c statistic HEART, 0.83, HEART-adj, 0.85). In comparison to HEART, HEART-adj proved in a decision curve analysis clinically useful for decision thresholds over 25%. Nevertheless, the original HEART classified patients better than HEART-adj (net reclassification improvement = 14.1%). CONCLUSION: The previously chosen weights of the 5 elements of the HEART score are supported by multivariable statistical analyses, although some improvement in calibration and discrimination is possible by adapting the score. The gain in clinical usefulness is relatively small and supports the use of either the original or adjusted HEART score in daily practice. PMID- 27183255 TI - Utility of the Diamond-Forrester Classification in Stratifying Acute Chest Pain in an Academic Chest Pain Center. AB - BACKGROUND: Because the Diamond-Forrester (DF) model is predictive of obstructive coronary artery disease (CAD), it is often used to risk stratify acute chest pain patients. We sought to further evaluate the clinical utility of the DF model within a chest pain evaluation center. METHODS: Consecutive patients with chest pain and no known CAD or evidence of active ischemia were asked to participate in a prospective registry. Patients were classified based on cardiovascular risk factors, age, and DF classification. We compared data from the emergency department course, Duke Activity Status Index (DASI) and Seattle Angina Questionnaire (SAQ), hospitalization rates, and results of testing between patients with typical angina and all others. Multivariate logistic regression was also used to assess for predictors of CAD by computed tomography coronary angiography (CTCA) or positive exercise treadmill testing (ETT). RESULTS: Among 209 patients, 163 had atypical/noncardiac and 46 had typical chest pain. The SAQ and DASI scores were lower in the typical chest pain group (indicating more severe impairment), which were not statistically significantly different. There were no significant differences in risk factors or the results of CTCA, ETT, or cardiac catheterization. In the regression analysis, SAQ score, DASI score, and DF classification were not predictive of CAD by CTCA. Worsening angina frequency scores on the SAQ were marginally associated with positive ETT (OR, 1.04; P=0.04). CONCLUSION: In a contemporary low-risk acute chest pain population, typical angina, as defined by the DF classification, was not predictive of CAD or useful for identifying patients with higher symptom burden. PMID- 27183256 TI - Association of Early Stress Testing with Outcomes for Emergency Department Evaluation of Suspected Acute Coronary Syndrome. AB - BACKGROUND: Professional society guidelines suggest early stress testing (within 72 hours) after an emergency department (ED) evaluation for suspected acute coronary syndrome (ACS). However, there is increasing concern that current practice results in over-testing without evidence of benefit. We test the hypothesis that early stress testing improves outcomes. METHODS: We analyzed prospectively collected data from 9 EDs on patients with suspected ACS, 1999 2001. We excluded patients with an ED diagnosis of ACS. The primary outcome was 30-day major adverse cardiac events (MACEs), including all-cause death, acute myocardial infarction, and revascularization. We used the HEART score to determine pretest ACS risk (low, intermediate, and high). To mitigate potential confounding, patients with and without early stress testing were matched within pretest risk strata in a 1:2 ratio using propensity scores. RESULTS: Of 7127 potentially eligible patients, 895 (13%) received early stress testing. The analytic cohort included 895 patients with early stress testing matched to 1790 without early stress testing. The overall 30-day MACE rate in both the source and analytic population was 3%. There were no baseline imbalances after propensity score matching (P > 0.1 for more than 30 variables). There was no association between early stress testing and 30-day MACE [odds ratio, 1.0; 95% confidence interval (CI), 0.6-1.7]. There was no effect modification by pretest risk (low: odds ratio, 1.0; 95% CI, 0.2-3.7; intermediate: 1.2; 95% CI, 0.6-2.6; high: 0.4; 95% CI, 0.1-1.6). CONCLUSIONS: Early stress testing is not associated with reduced MACE in patients evaluated for suspected ACS. Early stress testing may have limited value in populations with low MACE rate. PMID- 27183257 TI - Effect of Baseline Red Blood Cell Distribution Width on Short- and Intermediate term Mortality of Patients Under Primary Percutaneous Coronary Intervention: A Survival Analysis. AB - OBJECTIVE: Considering the limited studies specifically evaluating the role of Red blood cell distribution width (RDW) in primary percutaneous coronary intervention (PCI), we aimed to investigate the role of baseline RDW in short- and intermediate-term cardiovascular events in ST-elevation myocardial infarction patients under primary PCI. METHODS: This is a historical cohort registry analysis of 1161 patients with ST-elevation myocardial infarction under primary PCI. According to inclusion criteria, 838 patients were allocated for analysis. Patients with RDW levels of 13.6% or higher were considered as high RDW group (third tertile). All the individuals were followed up for in-hospital and 6-month mortality along with readmission and composite major adverse cardiac events. RESULTS: In-hospital deaths occurred in 53 (6.3%) patients and at 6-month follow up 79 (9.4%) cases of mortality were documented. In-hospital and 6-month mortalities showed a significant trend in favor of high RDW group (13.3% vs. 5.9%, P = 0.003; 19.7% vs. 7.9%, P < 0.001, respectively). Multivariate analysis showed that high RDW was significantly and independently associated with higher rates of 6-month mortality (hazard ratio: 2.909; 95% confidence interval: 1.166 7.257; P = 0.022). RDW was also a significant predictor for 6-month mortality independent of anemia (hazard ratio: 2.811; 95% confidence interval: 1.047-7.551; P = 0.040). CONCLUSIONS: We found a significant association between high RDW and in-hospital and 6-month mortality as well as the occurrence of major adverse cardiac event. Meanwhile RDW was found to be a significant predictor for 6-month mortality independent of anemia. Thus, it would be beneficial to use RDW as a risk stratification index to identify high risk intent-to-treat patients. PMID- 27183258 TI - The 2015 Nobel Prize in Chemistry The Discovery of Essential Mechanisms that Repair DNA Damage. AB - The Royal Swedish Academy awarded the Nobel Prize in Chemistry for 2015 to Tomas Lindahl, Paul Modrich and Aziz Sancar for their discoveries in fundamental mechanisms of DNA repair. This pioneering research described three different essential pathways that correct DNA damage, safeguard the integrity of the genetic code to ensure its accurate replication through generations, and allow proper cell division. Working independently of each other, Tomas Lindahl, Paul Modrich and Aziz Sancar delineated the mechanisms of base excision repair, mismatch repair and nucleotide excision repair, respectively. These breakthroughs challenged and dismissed the early view that the DNA molecule was very stable, paving the way for the discovery of human hereditary diseases associated with distinct DNA repair deficiencies and a susceptibility to cancer. It also brought a deeper understanding of cancer as well as neurodegenerative or neurological diseases, and let to novel strategies to treat cancer. PMID- 27183270 TI - Quorum sensing control of Type VI secretion factors restricts the proliferation of quorum-sensing mutants. AB - Burkholderia thailandensis uses acyl-homoserine lactone-mediated quorum sensing systems to regulate hundreds of genes. Here we show that cell-cell contact dependent type VI secretion (T6S) toxin-immunity systems are among those activated by quorum sensing in B. thailandensis. We also demonstrate that T6S is required to constrain proliferation of quorum sensing mutants in colony cocultures of a BtaR1 quorum-sensing signal receptor mutant and its parent. However, the BtaR1 mutant is not constrained by and outcompetes its parent in broth coculture, presumably because no cell contact occurs and there is a metabolic cost associated with quorum sensing gene activation. The increased fitness of the wild type over the BtaR1 mutant during agar surface growth is dependent on an intact T6SS-1 apparatus. Thus, quorum sensing activates B. thailandensis T6SS-1 growth inhibition and this control serves to police and constrain quorum-sensing mutants. This work defines a novel role for T6SSs in intraspecies mutant control. PMID- 27183269 TI - Two-way communication between SecY and SecA suggests a Brownian ratchet mechanism for protein translocation. AB - The essential process of protein secretion is achieved by the ubiquitous Sec machinery. In prokaryotes, the drive for translocation comes from ATP hydrolysis by the cytosolic motor-protein SecA, in concert with the proton motive force (PMF). However, the mechanism through which ATP hydrolysis by SecA is coupled to directional movement through SecYEG is unclear. Here, we combine all-atom molecular dynamics (MD) simulations with single molecule FRET and biochemical assays. We show that ATP binding by SecA causes opening of the SecY-channel at long range, while substrates at the SecY-channel entrance feed back to regulate nucleotide exchange by SecA. This two-way communication suggests a new, unifying 'Brownian ratchet' mechanism, whereby ATP binding and hydrolysis bias the direction of polypeptide diffusion. The model represents a solution to the problem of transporting inherently variable substrates such as polypeptides, and may underlie mechanisms of other motors that translocate proteins and nucleic acids. PMID- 27183271 TI - Nucleosome Binding Alters the Substrate Bonding Environment of Histone H3 Lysine 36 Methyltransferase NSD2. AB - Nuclear receptor-binding SET domain protein 2 (NSD2) is a histone H3 lysine 36 (H3K36)-specific methyltransferase enzyme that is overexpressed in a number of cancers, including multiple myeloma. NSD2 binds to S-adenosyl-l-methionine (SAM) and nucleosome substrates to catalyze the transfer of a methyl group from SAM to the epsilon-amino group of histone H3K36. Equilibrium binding isotope effects and density functional theory calculations indicate that the SAM methyl group is sterically constrained in complex with NSD2, and that this steric constraint is released upon nucleosome binding. Together, these results show that nucleosome binding to NSD2 induces a significant change in the chemical environment of enzyme-bound SAM. PMID- 27183273 TI - Optical Absorption Spectra and Excitons of Dye-Substrate Interfaces: Catechol on TiO2(110). AB - Optimizing the photovoltaic efficiency of dye-sensitized solar cells (DSSC) based on staggered gap heterojunctions requires a detailed understanding of sub-band gap transitions in the visible from the dye directly to the substrate's conduction band (CB) (type-II DSSCs). Here, we calculate the optical absorption spectra and spatial distribution of bright excitons in the visible region for a prototypical DSSC, catechol on rutile TiO2(110), as a function of coverage and deprotonation of the OH anchoring groups. This is accomplished by solving the Bethe-Salpeter equation (BSE) based on hybrid range-separated exchange and correlation functional (HSE06) density functional theory (DFT) calculations. Such a treatment is necessary to accurately describe the interfacial level alignment and the weakly bound charge transfer transitions that are the dominant absorption mechanism in type-II DSSCs. Our HSE06 BSE spectra agree semiquantitatively with spectra measured for catechol on anatase TiO2 nanoparticles. Our results suggest deprotonation of catechol's OH anchoring groups, while being nearly isoenergetic at high coverages, shifts the onset of the absorption spectra to lower energies, with a concomitant increase in photovoltaic efficiency. Further, the most relevant bright excitons in the visible region are rather intense charge transfer transitions with the electron and hole spatially separated in both the [110] and [001] directions. Such detailed information on the absorption spectra and excitons is only accessible via periodic models of the combined dye-substrate interface. PMID- 27183272 TI - The role of 5-aminolevulinic acid in enhancing surgery for high-grade glioma, its current boundaries, and future perspectives: A systematic review. AB - 5-Aminolevulinic acid (5-ALA) has been approved as an intraoperative adjunct in glioma surgery in Europe, but not North America. A systematic review was conducted to assess the evidence regarding 5-ALA as a surgical adjunct. The MEDLINE, EMBASE, and CENTRAL databases were searched, using terms relevant to "5 ALA" and "high-grade gliomas." Included studies were based on adults aged >=18 years who underwent surgical resection/biopsy. No language or date limitations were used. Forty-three studies (1830 patients) were identified. Thirty-six were coordinated by European countries, 2 were in the United States, and none were in Canada. One was randomized, 28 were prospective, and 14 were retrospective. Twenty-six studies assessed the utility of 5-ALA as a diagnostic tool, 24 assessed its influence on the extent of resection (EOR), 9 assessed survival, and 22 reported adverse events. 5-ALA had high sensitivity and positive predictive value, whereas its specificity increased with additional adjuncts. The EOR increased with 5-ALA, but only progression-free survival was significantly influenced. Reporting of adverse events was not systematic. The use of 5-ALA improved tumor visualization and thus enabled a greater EOR and perhaps increased survival. However, additional adjuncts may be necessary for maximizing the specificity of resection and patient safety. Additional parameters, such as patient quality of life and health economic analyses, would be informative. Thus, additional systematic collection of prospective evidence may be necessary for the global incorporation of this potentially valuable surgical adjunct into routine practice. Cancer 2016;122:2469-78. (c) 2016 American Cancer Society. PMID- 27183274 TI - Poor sleep predicts subacute postconcussion symptoms following mild traumatic brain injury. AB - The primary objective was to determine if poor sleep predicts postconcussion symptoms in the subacute period after mild traumatic brain injury (TBI). The impact of poor sleep pre- and post-injury was examined. The research design was cross-sectional. After screening to detect response invalidity, 61 individuals with a self-reported history of mild TBI 1-to-6 months prior answered an online fixed order battery of standardized questionnaires assessing their sleep (current and preinjury) and persistent postconcussion symptoms (Neurobehavioral Symptom Inventory, minus sleep, and fatigue items). The sleep measures were the Insomnia Severity Index, Epworth Sleepiness Scale, a single Likert-scale pre-injury sleep quality rating, and two PROMISTM measures (sleep-related impairment and sleep disturbance). After controlling for the effects of preinjury sleep quality and demographics, the combination of the sleep measures made a significant contribution to the outcome (F[8,58] = 4.013, p = .001, [Formula: see text]). Only current sleep-related impairment (beta = .60, p < .05) made a significant and unique contribution to neurobehavioral symptoms. Preinjury sleep was not a predictor (beta = -.19, p > .05), although it contributed 3% of the variance in NSI scores after controlling for demographics. Sleep-related impairment is a modifiable factor. As a significant contributor to neurobehavioral symptoms, treatment for post-injury sleep-related impairment warrants further attention. PMID- 27183275 TI - Radiological protection and the exposure of animals as patients in veterinary medicine. AB - It is apparent that most of the techniques that make use of ionising radiation in human medical practices are now being applied in veterinary medicine. Steps are being taken by the IAEA to provide guidance for humans involved in such practices, but there appears to be no international initiative that considers the protection or welfare of the animal as a patient. There is therefore a risk that the deliberate exposure of an animal, particularly in the therapeutic application of radiation, could do more harm than good. In the light of recent developments in dosimetric modelling and the application of known effects of radiation on different types of animals, for the purposes of the protection of biota in an environmental context, it is argued that it would be sensible now to start a serious consideration of this issue. Some suggestions are made with regard to a number of areas that could be considered further, both specifically and with regard to the field of radiological protection as a whole. PMID- 27183276 TI - A photoacoustic immunoassay for biomarker detection. AB - Challenges in protein biomarker analysis include insufficient sensitivity for detecting low-abundance biomarkers, poor measurement reproducibility, and the high costs and large footprints of detection systems. To address these issues, a new detection modality was developed for analyzing protein biomarkers based on the plasmon-enhanced photoacoustic (PA) effect. The detection modality employed a heterogeneous immunoassay scheme and used gold nanoparticles (AuNPs) as the signal reporter. Due to their localized plasmon resonance, AuNPs can strongly interact with intensity-modulated laser excitation and generate strong PA signals, which are subsequently sensed and quantified using a microphone. As an example, the performance of the PA immunoassay was evaluated by detecting the human interleukin 8 chemokine. The PA immunoassay provided approximately 143* lower limit of detection (LOD) than observed with the gold standard enzyme-linked immunosorbent assay - a decrease from 23pg/mL to 0.16pg/mL. In addition to the significant performance improvement in terms of the LOD, the PA immunoassay also offers advantages in terms of compatibility with low-cost instruments and the long-term stability of assay results. PMID- 27183277 TI - Dual detection of nitrate and mercury in water using disposable electrochemical sensors. AB - Here we report a disposable, cost effective electrochemical paper-based sensor for the detection of both nitrate and mercury ions in lake water and contaminated agricultural runoff. Disposable carbon paper electrodes were functionalized with selenium particles (SePs) and gold nanoparticles (AuNPs). The AuNPs served as a catalyst for the reduction of nitrate ions using differential pulse voltammetry techniques. The AuNPs also served as a nucleation sites for mercury ions. The SePs further reinforced this mercury ion nucleation due to their high binding affinity to mercury. Differential pulse stripping voltammetry techniques were used to further enhance mercury ion accumulation on the modified electrode. The fabricated electrode was characterized by scanning electron microscopy, energy dispersive X-ray spectroscopy, and electrochemistry techniques. The obtained results show that the PEG-SH/SePs/AuNPs modified carbon paper electrode has a dual functionality in that it can detect both nitrate and mercury ions without any interference. The modified carbon paper electrode has improved the analytical sensitivity of nitrate and mercury ions with limits of detection of 8.6uM and 1.0ppb, respectively. Finally, the modified electrode was used to measure nitrate and mercury in lake water samples. PMID- 27183278 TI - Rapid and facile ratiometric detection of an anthrax biomarker by regulating energy transfer process in bio-metal-organic framework. AB - A ratiometric fluorescent sensor based on luminescent bio-metal-organic framework was prepared by exchanging both Tb(3+) and Eu(3+) cations into anionic bio-MOF-1. Due to a highly efficient energy transfer from Tb(3+) to Eu(3+) (>89%), emission color of Tb/Eu@bio-MOF-1 was orange-red even though Tb(3+) was the dominant content in this Tb/Eu co-doping material. More interestingly, this energy transfer process could be modulated by dipicolinic acid (DPA), an unique biomarker for bacillus spores. With DPA addition, corresponding DPA-to-Tb(3+) energy transfer was gradually enhanced while the energy transfer from Tb(3+) to Eu(3+) was significantly weakened. By regulating the energy transfer process in Tb/Eu@bio-MOF-1, visual colorimetric sensing of DPA in porous MOF was realized for the first time. Detection limit of Tb/Eu@bio-MOF-1 for DPA was 34nM, which was much lower than an infectious dosage of Bacillus anthracis spores (60MUM) for human being. Besides, Tb/Eu@bio-MOF-1 showed a remarkable selectivity over other aromatic ligands and amino acids. More importantly, this porous ratiometric sensor worked equally well in human serum. These particularly attractive features of Tb/Eu@bio-MOF-1 made the direct, rapid and naked-eye detection of DPA for practical application possible. PMID- 27183279 TI - Simultaneous photoelectrochemical and visualized immunoassay of beta-human chorionic gonadotrophin. AB - Herein, on the basis of the alkaline phosphate (ALP) induced reaction, a simultaneous photoelectrochemical (PEC) and visualized immunoassay has been established for the detection of beta-human chorionic gonadotrophin (beta-HCG). Specifically, in the proposed system, ALP stimulated the oxidative hydrolyzing transformation of 5-bromo-4-chloro-3-indoyl phosphate (BCIP) to an indigo precipitation, generating an insulating layer that impeded the interfacial mass and electron transfer and thus the photocurrent production. Meanwhile, a visualized detection could be performed according to the change of color intensity. Upon proper experimental conditions, the protocol possessed a detection range of 0.5-1000IU/L with a detection limit of (0.20+/-0.011)IU/L toward beta-HCG. With high sensitivity and specificity, this work presents the first general protocol for simultaneous PEC and visualized detection, which could be easily extended to addressing numerous other targets. PMID- 27183280 TI - A versatile nanomachine for the sensitive detection of platelet-derived growth factor-BB utilizing a G-quadruplex-selective iridium(III) complex. AB - The novel iridium(III) complex 1 was found to be highly selective for G quadruplex DNA, and was employed for the development of a versatile nanomachine. In the nanomachine, the single-stranded DNA (ssDNA) oligonucleotide ON1 hybridizes with the hairpin DNA oligonucleotide ON2, leading to the formation of a 5'-recessed double-stranded DNA (dsDNA) structure and the simultaneous release of a G-rich DNA sequence, which folds into a G-quadruplex motif that is recognized by complex 1. Upon the addition of Exo III, the dsDNA substrate is digested leading to the liberation of ON1 ssDNA, which enters a new cycle of the nanomachine. This nanomachine was successfully used to detect PDGF-BB by combination with a simple pre-procedure module, and exhibited a linear response between luminescence intensity and PDGF-BB concentration in the range of 10 to 300pM (R(2)=0.992), with a limit of detection for PDGF-BB of 10pM. This assay was highly selective for PDGF-BB over other proteins, and exhibited potential use in biological sample analysis. Moreover, the versatility of the nanomachine was demonstrated by adapting the nanomachine for the detection of thrombin by simply changing the pre-procedure module. PMID- 27183281 TI - Label-free bimodal waveguide immunosensor for rapid diagnosis of bacterial infections in cirrhotic patients. AB - Spontaneous bacterial peritonitis is an acute bacterial infection of ascitic fluid; it has a high incidence in cirrhotic patients and it is associated with high mortality. In such a situation, early diagnosis and treatment is crucial for the survival of the patient. However, bacterial analysis in ascitic fluid is currently based on culture methods, which are time-consuming and laborious. We report here the application of a photonic interferometer biosensor based on a bimodal waveguide (BiMW) for the rapid and label-free detection of bacteria directly in ascitic fluid. The device consists of a straight waveguide in which two modes of the same polarization interfere while interacting with the external medium through their evanescent fields. A bimolecular event occurring on the sensor area of the device (e.g. capturing bacteria) will differently affect each light mode, inducing a variation in the phase of the light exiting at the output of the waveguide. In this work, we demonstrate the quantitative detection of Bacillus cereus in buffer medium and Escherichia coli in undiluted ascitic fluid from cirrhotic patients. In the case of Bacillus cereus detection, the device was able to specifically detect bacteria at relevant concentrations in 12.5min and in the case of Escherichia coli detection, the analysis time was 25min. Extrapolation of the data demonstrated that the detection limits of the biosensor could reach few bacteria per milliliter. Based on the results obtained, we consider that the BiMW biosensor is positioned as a promising new clinical tool for user-friendly, cost-effective and real-time microbiological analysis. PMID- 27183282 TI - A fluorescent assay for gamma-glutamyltranspeptidase via aggregation induced emission and its applications in real samples. AB - gamma-Glutamyl transpeptidase (GGT) plays crucial roles in some physiological processes. Herein a turn-on fluorescent probe for gamma-glutamyl transpeptidase (GGT) assay based on aggregation-induced-emission (AIE) effect and the enzyme induced transformation of hydrophilicity to hydrophobicity has been developed by functionalizing tetraphenylethylene (TPE) derivative with two gamma-glutamyl amide groups, which simultaneously work as recognition units and hydrophilic groups. When the gamma-glutamyl amide groups are cleaved through GGT enzymatic reaction, the hydrophobic reaction product readily aggregate and correspondingly strong blue fluorescence can be observed, as a result of activated AIE process. By virtue of the probe's good solubility in totally aqueous solution, high sensitivity and excellent photostability, the probe can be employed to detect GGT level in human serum samples. Furthermore, the probe can be used for imaging endogenous GGT in living A2780 cells. Hence, the probe holds great promise for acting as a convenient one-step straightforward assay for GGT detection in diagnostic-related applications, and also it could provide a useful approach for conducting pathological analysis for diseases involving GGT. PMID- 27183283 TI - SERS nanoprobes for the monitoring of endogenous nitric oxide in living cells. AB - Nitric Oxide (NO) is a significant gaseous signalling molecule in various pathological and physiological pathways, whereas many of its functions are still ambiguous in part because of the shortage of powerful detection approaches. Herein, we present a type of reaction-based surface-enhanced Raman scattering (SERS) nanoprobes, o-phenylenediamine-modified gold nanoparticles (AuNPs/OPD), to detect the level of the endogenous NO in living cells. The detection is achieved through the SERS variation of AuNPs/OPD caused by the reaction between NO and OPD on the surface of AuNPs. The proposed SERS nanoprobes have a good stability and a rapid response to NO within 30s Moreover, as a result of the reaction specificity coupled with SERS fingerprinting, AuNPs/OPD nanoprobes demonstrate high selectivity towards NO over other biologically relevant species with a sensitivity at 10(-7)M level. Thereby, this SERS strategy can be used for monitoring NO that is endogenously produced in living macrophages, indicating immense potential in studying NO-involved pathophysiological processes in biological systems. PMID- 27183284 TI - MWCNTs based high sensitive lateral flow strip biosensor for rapid determination of aqueous mercury ions. AB - Here, we describe a disposable multi-walled carbon nanotubes (MWCNTs) labeled nucleic acid lateral flow strip biosensor for rapid and sensitive detection of aqueous mercury ions (Hg(2+)). Unlike the conventional colloidal gold nanoparticle based strip biosensors, the carboxylated MWCNTs were selected as the labeling substrate because of its high specific surface area for immobilization of recognition probes, improved stability and enhanced detection sensitivity of the strip biosensor. Combining the sandwich-type of T-Hg(2+)-T recognition mechanism with the optical properties of MWCNTs on lateral flow strip, optical black bands were observed on the lateral flow strips. Parameters (such as membrane category, the MWCNTs concentration, the amount of MWCNT-DNA probe, and the volume of the test probe) that govern the sensitivity and reproducibility of the sensor were optimized. The response of the optimized biosensor was highly linear over the range of 0.05-1ppb target Hg(2+), and the detection threshold was estimated at 0.05 ppb within a 15-min assay time. The sensitivity was 10-fold higher than the conventional colloidal gold based strip biosensor. More importantly, the stability of the sensor was also greatly improved with the usage of MWCNTs as the labeling. PMID- 27183285 TI - Development and comparison of immunochromatographic strips with three nanomaterial labels: Colloidal gold, nanogold-polyaniline-nanogold microspheres (GPGs) and colloidal carbon for visual detection of salbutamol. AB - In this study, the three nanomaterials: colloidal gold, nanogold-polyaniline nanogold microspheres (GPGs) and colloidal carbon were respectively labeled with the antibody against salbutamol (SAL). We aimed to develop immunochromatographic strips with these nanomaterial labels and determine their performance in visual detection of SAL. For the colloidal gold-based strip, the detection limit of SAL was 1.0ugL(-1) in standard solution and 5.0ugkg(-1) in meat samples. For the GPG- and colloidal carbon-based strips, the limit of detection was 2.0ugL(-1) in standard solution and 10ugkg(-1) in meat samples. The results obtained using the test strips were found to be highly consistent with those obtained using a commercial kit, indicating the high accuracy of these strips. The three strips were also found to be stable up to 18 weeks under laboratory conditions. In terms of sensitivity, the colloidal gold-based strip was slightly better than the other two. For the GPG- and colloidal carbon-based strips, the difference between the results obtained for different batches was small (high consistency), and the stability was much better than that of the colloidal gold-based one. Our results indicate that colloidal carbon can be used as a label in immunochromatographic tests; it can also help reduce the cost involved and scale-up the production. The use of immunochromatographic test strips labeled with colloidal carbon can be a rapid and inexpensive method for SAL assays in on-site applications. PMID- 27183286 TI - A novel electrochemical immunosensor based on nonenzymatic Ag@Au-Fe3O4 nanoelectrocatalyst for protein biomarker detection. AB - A hybrid nanostructure of Fe3O4 nanospheres and Ag@Au nanorods prepared by polydopamine coating was utilized as nanoelectrocatalyst to construct a novel sandwich-type electrochemical immunosensor. Ag@Au-Fe3O4 nanohybrid modified electrode exhibited much better electrocatalytic activity toward the reduction of hydrogen peroxide than Fe3O4 nanospheres or Ag@Au nanorods due to the synergetic catalytic effect. The immunosensor was prepared by immobilizing the capture antibodies on the amine-terminated nanocomposite of carbon nanofibers-chitosan, whilst the trace tag was prepared by loading detection antibodies on the Ag@Au Fe3O4 nanocomposite. After the parameter optimization, the amperometric signal increased linearly with human IgG concentration in the broad range of 0.1pgmL(-1) to 5MUgmL(-1) with a detection limit of 50fgmL(-1). Meanwhile, the enzyme-free catalyst based immunosensor also showed acceptable selectivity, reproducibility and stability. PMID- 27183287 TI - Lab-on-a-disc agglutination assay for protein detection by optomagnetic readout and optical imaging using nano- and micro-sized magnetic beads. AB - We present a biosensing platform for the detection of proteins based on agglutination of aptamer coated magnetic nano- or microbeads. The assay, from sample to answer, is integrated on an automated, low-cost microfluidic disc platform. This ensures fast and reliable results due to a minimum of manual steps involved. The detection of the target protein was achieved in two ways: (1) optomagnetic readout using magnetic nanobeads (MNBs); (2) optical imaging using magnetic microbeads (MMBs). The optomagnetic readout of agglutination is based on optical measurement of the dynamics of MNB aggregates whereas the imaging method is based on direct visualization and quantification of the average size of MMB aggregates. By enhancing magnetic particle agglutination via application of strong magnetic field pulses, we obtained identical limits of detection of 25pM with the same sample-to-answer time (15min 30s) using the two differently sized beads for the two detection methods. In both cases a sample volume of only 10ul is required. The demonstrated automation, low sample-to-answer time and portability of both detection instruments as well as integration of the assay on a low-cost disc are important steps for the implementation of these as portable tools in an out-of-lab setting. PMID- 27183288 TI - The Latest Updates and Management of Endophthalmitis. PMID- 27183289 TI - Incidence and Risk Factors of Retinopathy of Prematurity From 2 Neonatal Intensive Care Units in a Hong Kong Chinese Population. AB - PURPOSE: To determine the incidence and risk factors of retinopathy of prematurity (ROP) in very low birth weight (VLBW) preterm Chinese infants. DESIGN: Retrospective review. METHODS: Medical records were reviewed for all neonates screened for ROP between January 2007 and December 2012 in Hong Kong. Screening was offered to VLBW (<=1500 g) and/or preterm (gestation, <=32 weeks) neonates using the Royal College of Ophthalmologists ROP guideline and the International Classification of ROP by 3 pediatric ophthalmologists. Maternal and neonatal covariates were analyzed using univariate and multivariable logistic regression analyses for both ROP and type 1 ROP. RESULTS: Of the 513 screened infants, the mean gestational age (GA) was 30.0 +/- 2.5 weeks and the mean birth weight (BW) was 1232.6 +/- 325.2 g. The incidence of ROP and type 1 ROP was 18.5% and 3.7%, respectively. In univariate analysis, a lighter BW, lower GA, blood transfusion, patent ductus arteriosus, nonsteroidal anti-inflammatory drug use, postnatal hypotension, inotropes usage, low Apgar scores, sepsis, mechanical ventilation, supplementary oxygen use, respiratory distress syndrome, anemia, surfactant use, and bronchopulmonary dysplasia were found to be associated with the development of both ROP and type 1 ROP (P < 0.05). In multivariable logistic regression analysis, BW, GA, and intraventricular hemorrhage were significant risk factors for ROP. Preeclampsia and eclampsia were the only protective factors for ROP development on multivariable logistic regression analysis (P = 0.02). CONCLUSIONS: In VLBW preterm Chinese infants, lower GA, lighter BW, and intraventricular hemorrhage were significant risk factors for ROP, whereas preeclampsia and eclampsia were protective. PMID- 27183290 TI - Eye Injury Prevention for the Pediatric Population. AB - Each year an estimated 3.3 to 5.7 million pediatric eye injuries occur worldwide. It is widely reported that 90% of ocular injuries are preventable. Our aim was to identify legislation and policies, education, and mandatory eye protection strategies that have successfully contributed to reducing rates of children's eye injuries. A literature search was conducted using the terms "pediatric" or "children" or "adolescent" and "ocular" or "eye" and "protection" or "injury prevention." Articles were retrieved based on titles and abstracts and assessed in the context of our research question. Strategies identified aimed at reducing ocular trauma fell into 3 broad categories: legislation and policies, education, and personal eye protection. Policies including restrictions on the sale and supply of certain consumer products, mandatory vehicle seatbelts, and laminated windscreens in vehicles have assisted in reducing children's eye injuries. Educational tools aimed at children and their caregivers have been effective in changing attitudes to eye health and safety. Effective pediatric eye injury prevention systems require a multifactorial approach combining legislation, policies, standards, education, and personal eye protection to limit exposure to ocular hazards. A paucity of standardized measurement and lack of funding have limited advances in the field of children's eye injury prevention. Improved eye injury surveillance and research funding along with collaboration with health care providers are important components for strategies to prevent pediatric ocular trauma. PMID- 27183291 TI - Advances in Refractive Surgery: June 2014 to July 2015. AB - PURPOSE: The objective of this study was to review the advances in the field of refractive surgery as reported in the peer-reviewed literature during the previous year. DESIGN: A literature review. METHODS: In this review, we highlight the most pertinent articles in the field from June 2014 to the end of July 2015. RESULTS: This past year has seen a growing body of research on small-incision lenticule extraction, presbyopic inlays, and phakic intraocular lenses, as more clinicians are adopting these techniques into their armamentarium. CONCLUSIONS: Laser-assisted in situ keratomileusis and photorefractive keratectomy continue to dominate the keratorefractive literature, as they remain the most frequently performed refractive surgeries. PMID- 27183292 TI - Regarding 'Management of Primary Angle-Closure Glaucoma'. PMID- 27183293 TI - Author's Reply. PMID- 27183294 TI - Prevalence of Diabetic Retinopathy in a Population of Diabetics From the Middle East With Microvascular Ocular Motor Palsies. AB - BACKGROUND: Vascular risk factors are increasing rapidly in the Middle East. Growing inactivity and obesity have contributed to an epidemic of Type 2 diabetes mellitus (DM) in the Arab population. Microvascular palsies of the third, fourth, and sixth cranial nerves, which occur in an isolated manner, are relatively common in patients with DM, hypertension, or other vascular risk factors. METHODS: In this retrospective analysis, patients with diabetes with microvascular palsies were assessed for the prevalence of diabetic retinopathy (DR). We compared these data with the prevalence of DR in the general population of diabetics in Saudi Arabia and to a similar published study done in an American population. RESULTS: In total, 126 patients with diabetes were included in the study. The sixth nerve was most frequently involved in 67 patients (53%). Seventy seven patients (61%) had DR, compared with 49 (39%) without DR. The prevalence of DR in the general population of Saudi patients with diabetes ranged from 30% to 36.1%. CONCLUSIONS: Our study demonstrated a higher prevalence of DR in patients with microvascular palsies compared with the general population of patients with diabetes in the Arab population. This is in contrast to a previous study in an American population. Our results might be secondary to differences between the 2 populations, in particular, the continued increase in the prevalence of vascular risk factors (mainly diabetes) and poor control of these risk factors in the Middle East. PMID- 27183295 TI - A Needs Assessment of the Number of Comprehensive Addiction Care Physicians Required in a Canadian Setting. AB - OBJECTIVE: Medical professionals adequately trained to prevent and treat substance use disorders are in short supply in most areas of the world. Whereas physician training in addiction medicine can improve patient and public health outcomes, the coverage estimates have not been established. We estimated the extent of the need for medical professionals skilled in addiction medicine in a Canadian setting. METHODS: We used Monte-Carlo simulations to generate medians and 95% credibility intervals for the burden of alcohol and drug use harms, including morbidity and mortality, in British Columbia, by geographic health region. We obtained prevalence estimates for the models from the Medical Services Plan billing, the Discharge Abstract Database data, and the government surveillance data. We calculated a provider availability index (PAI), a ratio of the size of the labor force per 1000 affected individuals, for each geographic health region, using the number of American Board of Addiction Medicine certified physicians in each area. RESULTS: Depending on the data source used for population estimates, the availability of specialized addiction care providers varied across geographic health regions. For drug-related harms, we found the highest PAI of 23.72 certified physicians per 1000 affected individuals, when using the Medical Services Plan and Discharge Abstract Database data. Drawing on the surveillance data, the drug-related PAI dropped to 0.46. The alcohol-related PAI ranged between 0.10 and 86.96 providers, depending on data source used for population estimates. CONCLUSIONS: Our conservative estimates highlight the need to invest in healthcare provider training and to develop innovative approaches for more rural health regions. PMID- 27183296 TI - Cell migration and organization in three-dimensional in vitro culture driven by stiffness gradient. AB - Durotaxis, a phenomenon that cells move according to changes in stiffness of the extra cellular matrix, has emerged as a crucial parameter controlling cell migration behavior. The current study provides a simple method to generate three dimensional continuous stiffness variations without changing other physical characteristics of the extra cellular environment. Using Finite Element simulations, the stiffness and the stiffness gradient variations are evaluated quantitatively, leading to an analysis of the dependence of cell migration behavior on the substrate stiffness parameters. We tested various cell lines on several 3-D environments. The durotaxis results show that the cell migration velocity does not have any consistency with the stiffness of the substrate, rather it is more related to the stiffness gradient of the substrate. This finding suggests a new mechanism underlying the durotaxis phenomenon, highlighting the importance of the substrate stiffness gradient, rather than the stiffness itself. Biotechnol. Bioeng. 2016;113: 2496-2506. (c) 2016 Wiley Periodicals, Inc. PMID- 27183297 TI - The Incidence and Recurrence of Getting Lost in Community-Dwelling People with Alzheimer's Disease: A Two and a Half-Year Follow-Up. AB - Getting lost (GL) is a serious problem for people living with Alzheimer's disease (PwAD), causing psychological distress in both PwAD and caregivers, and increasing the odds of being institutionalized. It is thus important to identify risk factors for the GL events in PwAD. Between April 2009 and March 2012, we invited 185 community-dwelling PwAD and their caregivers to participate in this study. At the baseline, 95 had experienced GL (Group B); the remaining 90 (Group A) had not. We focused on the incidence of GL events and the associated factors by way of demographic data, cognitive function assessed by the Cognitive Ability Screening Instrument (CASI), and spatial navigation abilities as assessed by the Questionnaire of Everyday Navigational Ability (QuENA). After a 2.5-year period, the incidence of GL in Group A was 33.3% and the recurrence of GL in Group B was 40%. Multiple logistic regression analysis revealed that the inattention item on the QuENA and orientation item on the CASI had independent effects on the GL incidence, while the absence of a safety range was associated with the risk of GL recurrence. During the 2.5 years, the PwAD with GL incidence deteriorated more in the mental manipulation item on the CASI than those without. We suggest that before the occurrence of GL, the caregivers of PwAD should refer to the results of cognitive assessment and navigation ability evaluation to enhance the orientation and attention of the PwAD. Once GL occurs, the caregivers must set a safety range to prevent GL recurrence, especially for younger people. PMID- 27183298 TI - Peptide Tag-Induced Horseradish Peroxidase-Mediated Preparation of a Streptavidin Immobilized Redox-Sensitive Hydrogel. AB - Several methods have recently been reported for the preparation of redox sensitive hydrogels using enzymatic reactions, which are useful for encapsulating sensitive materials such as proteins and cells. However, most of the reported hydrogels is difficult to add further function efficiently, limiting the application of the redox-sensitive hydrogels. In this study, peptide sequences of HHHHHHC and GGGGY (Y-tag) were genetically fused to the N- and C-termini of streptavidin (C-SA-Y), respectively, and C-SA-Y was mixed with horseradish peroxidase and thiol-functionalized 4-arm polyethylene glycol to yield a redox sensitive C-SA-Y immobilized hydrogel (C-SA-Y gel). The C-SA-Y immobilized in the hydrogel retained its affinity for biotin, allowing for the incorporation of proteins and small molecules to hydrogel via biotin. C-SA-Y gel was further prepared within a water-in-oil (w/o) emulsion system to yield a nanosized hydrogel, to which any intracellular and cytotoxic agent can be modified, making it a potential drug delivery carrier. PMID- 27183300 TI - Tai Chi Versus Physical Therapy for Knee Osteoarthritis. PMID- 27183299 TI - Efficacy, Safety, and Tolerability of an Extended-Release Orally Disintegrating Methylphenidate Tablet in Children 6-12 Years of Age with Attention Deficit/Hyperactivity Disorder in the Laboratory Classroom Setting. AB - OBJECTIVE: Methylphenidate extended-release orally disintegrating tablets (MPH XR ODTs) represent a new technology for MPH delivery. ODTs disintegrate in the mouth without water and provide a pharmacokinetic profile that is consistent with once daily dosing. This study sought to determine the efficacy, safety, and tolerability of this novel MPH XR-ODT formulation in school-age children with attention-deficit/hyperactivity disorder (ADHD) in a laboratory classroom setting. METHODS: Children aged 6-12 years with ADHD (n = 87) were enrolled in this randomized, multicenter, double-blind, placebo-controlled, parallel, laboratory classroom study. The MPH XR-ODT dose was titrated to an optimized dose during a 4-week open-label period and maintained on that dose for 1 week. Participants (n = 85) were then randomized to receive their optimized dose of MPH XR-ODT or placebo once daily for 1 week (double blind), culminating in a laboratory classroom testing day. Efficacy was evaluated using the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Attention, Deportment, and Combined scores along with Permanent Product Measure of Performance (PERMP; Attempted and Correct) assessments. Onset and duration of drug action were also evaluated as key secondary endpoints. Safety assessments included adverse events (AEs), physical examinations, electrocardiograms (ECGs), and the Columbia Suicide Severity Rating Scale (C-SSRS). RESULTS: The average SKAMP-Combined score on the classroom study day was significantly better for the MPH XR-ODT group (n = 43) than for the placebo group (n = 39; p < 0.0001). The effect was evident at 1 hour and lasted through 12 hours postdose. The average SKAMP-Attention, SKAMP Deportment, PERMP-A, and PERMP-C scores were indicative of significantly greater ADHD symptom control for the MPH XR-ODT group. The most common AEs reported were decreased appetite, upper abdominal pain, headache, insomnia, upper respiratory tract infection, affect lability, irritability, cough, and vomiting. CONCLUSIONS: MPH XR-ODT was effective and well tolerated for the treatment of children with ADHD in a laboratory classroom setting. Clinical Trial Registry: NCT01835548 ( ClinicalTrials.gov ). PMID- 27183301 TI - Perspectives on the Transition From Bacterial Phytopathogen Genomics Studies to Applications Enhancing Disease Management: From Promise to Practice. AB - The advent of genomics has advanced science into a new era, providing a plethora of "toys" for researchers in many related and disparate fields. Genomics has also spawned many new fields, including proteomics and metabolomics, furthering our ability to gain a more comprehensive view of individual organisms and of interacting organisms. Genomic information of both bacterial pathogens and their hosts has provided the critical starting point in understanding the molecular bases of how pathogens disrupt host cells to cause disease. In addition, knowledge of the complete genome sequence of the pathogen provides a potentially broad slate of targets for the development of novel virulence inhibitors that are desperately needed for disease management. Regarding plant bacterial pathogens and disease management, the potential for utilizing genomics resources in the development of durable resistance is enhanced because of developing technologies that enable targeted modification of the host. Here, we summarize the role of genomics studies in furthering efforts to manage bacterial plant diseases and highlight novel genomics-enabled strategies heading down this path. PMID- 27183302 TI - Cercospora cf. flagellaris and Cercospora cf. sigesbeckiae Are Associated with Cercospora Leaf Blight and Purple Seed Stain on Soybean in North America. AB - Cercospora kikuchii has long been considered the causal agent of Cercospora leaf blight (CLB) and purple seed stain (PSS) on soybean, but a recent study found C. cf. flagellaris associated with CLB and PSS in Arkansas (United States) and Argentina. Here, we provide a broader perspective on the distribution of C. cf. flagellaris on soybean and alternate hosts within the United States (Arkansas, Louisiana, Mississippi, Missouri, and Kansas). We used a multilocus phylogenetic approach with data from actin, calmodulin, translation elongation factor 1-alpha, histone 3, the internal transcribed spacer region of rDNA and the mating-type locus to determine that two species, C. cf. flagellaris (200 of 205 isolates) and C. cf. sigesbeckiae (five of 205 isolates), are associated with CLB and PSS in the United States. In our phylogenetic analyses, species-level lineages were generally well-supported, though deeper-level evolutionary relationships remained unresolved, indicating that these genes do not possess sufficient phylogenetic signal to resolve the evolutionary history of Cercospora. We also investigated the potential for sexual reproduction in C. cf. flagellaris in Louisiana by determining the frequency of MAT1-1/MAT1-2 mating-type idiomorphs within the Louisiana population of C. cf. flagellaris. Though the MAT 1-2 idiomorph was significantly more common in our collection, the presence of both mating types suggests the potential for sexual reproduction exists. PMID- 27183304 TI - Impact of goal priority and goal conflict on the intention-health-behavior relationship: Tests on physical activity and other health behaviors. AB - OBJECTIVES: Goal intentions are the key proximal determinant of behavior in a number of key models applied to predicting health behavior. However, relatively little previous research has examined how characteristics of goals moderate the intention-health-behavior relations. The present research examined the effects of goal priority and goal conflict as moderators of the intention-health-behavior relationship. METHOD: The main outcome measures were self-reported performance of physical activity (Studies 1, 2, and 3) and other health behaviors (Study 4), and objectively measured physical activity (Study 3). Studies 1 and 4 used prospective correlational designs to predict later behavior from earlier cognitions. Studies 2 and 3 were experimental studies manipulating goal priority and goal conflict. Studies 1 and 2 used between-subjects designs while Studies 3 and 4 used within-subjects designs. RESULTS: Goal priority significantly moderated the intention-health-behavior relationship for physical activity (Study 1) and a range of protective and risk health behaviors (Study 4). Manipulations of goal priority significantly increased the intention-physical-activity relationship when self-reported (Study 2) and objectively measured (Study 3). In contrast, inconsistent effects were observed for goal conflict as an intention behavior moderator. CONCLUSIONS: When goal priority is high, then intentions are strong predictors of health behaviors. Further studies testing manipulations of goal conflict and in particular goal priority in combination with goal intentions are required to confirm their value as a means to change health behavior. (PsycINFO Database Record PMID- 27183303 TI - The Effect of Passive Heat Stress and Exercise-Induced Dehydration on the Compensatory Reserve During Simulated Hemorrhage. AB - Compensatory reserve represents the proportion of physiological responses engaged to compensate for reductions in central blood volume before the onset of decompensation. We hypothesized that compensatory reserve would be reduced by hyperthermia and exercise-induced dehydration, conditions often encountered on the battlefield. Twenty healthy males volunteered for two separate protocols during which they underwent lower-body negative pressure (LBNP) to hemodynamic decompensation (systolic blood pressure <80 mm Hg). During protocol #1, LBNP was performed following a passive increase in core temperature of ~1.2 degrees C (HT) or a normothermic time-control period (NT). During protocol #2, LBNP was performed following exercise during which: fluid losses were replaced (hydrated), fluid intake was restricted and exercise ended at the same increase in core temperature as hydrated (isothermic dehydrated), or fluid intake was restricted and exercise duration was the same as hydrated (time-match dehydrated). Compensatory reserve was estimated with the compensatory reserve index (CRI), a machine-learning algorithm that extracts features from continuous photoplethysmograph signals. Prior to LBNP, CRI was reduced by passive heating [NT: 0.87 (SD 0.09) vs. HT: 0.42 (SD 0.19) units, P <0.01] and exercise-induced dehydration [hydrated: 0.67 (SD 0.19) vs. isothermic dehydrated: 0.52 (SD 0.21) vs. time-match dehydrated: 0.47 (SD 0.25) units; P <0.01 vs. hydrated]. During subsequent LBNP, CRI decreased further and its rate of change was similar between conditions. CRI values at decompensation did not differ between conditions. These results suggest that passive heating and exercise-induced dehydration limit the body's physiological reserve to compensate for further reductions in central blood volume. PMID- 27183306 TI - The Effect of Self-Efficacy on Behavior and Weight in a Behavioral Weight-Loss Intervention. AB - OBJECTIVE: To determine whether eating self-efficacy (ESE) and physical activity self-efficacy (PASE) are predictive of dietary intake, physical activity, and weight change within a behavioral weight-loss intervention, and whether dietary intake and physical activity mediate relationships between self-efficacy and weight change. METHOD: The study sample included 246 participants from a randomized trial with complete data on study variables at 12 months. ESE, PASE, calories consumed, minutes of moderate-to-vigorous physical activity (MVPA), and weight were measured at baseline, 6, and 12 months. RESULTS: ESE at baseline was associated with 12-month percent weight loss (PWL), and was mediated by average calories consumed at 6 and 12 months. Change in ESE from baseline to 6 months was associated with calories consumed at 12 months and 12-month percent weight loss, but the mediated relationship was not significant. Baseline PASE was not associated with average MVPA at 6 and 12 months or 12-month PWL, but change in PASE from baseline to 6 months was associated with 12-month PWL through its effect on MVPA at 12 months. CONCLUSION: Increases in ESE and PASE during the active phase of the intervention are predictive of dietary intake, physical activity and weight loss at later points, but further research should include explorations of the reciprocal relationship between behavior and self-efficacy to better inform intervention strategies that target self-efficacy and promote behavior change. (PsycINFO Database Record PMID- 27183305 TI - Alcohol Interventions for Greek Letter Organizations: A Systematic Review and Meta-Analysis, 1987 to 2014. AB - OBJECTIVE: This meta-analysis examines the efficacy of interventions to reduce alcohol consumption and related problems among college student members of Greek letter organizations. METHOD: Studies were identified through electronic bibliographic database searches and reviews of reference sections of relevant articles, and studies were included if the study evaluated (a) an individual level alcohol intervention, (b) sampled fraternity or sorority members, and (c) measured alcohol consumption or problems. Included were 15 studies with 21 separate interventions (n = 6,026; 18% women). Independent raters coded sample, design, methodological features, and intervention content. Between- and within group weighted mean effect sizes were calculated using random-effects models. Potential moderators, determined a priori, examined variability in effect sizes. RESULTS: Interventions targeting fraternity or sorority members were not successful in reducing alcohol consumption and related problems relative to controls; however, participants in these interventions did reduce the quantity consumed on specific occasions and the frequency of drinking days from pre- to post-test. Interventions that addressed alcohol expectancies were associated with less alcohol consumption on specific occasions. Interventions that provided moderation strategies and skills-training, identified high-risk situations, or encouraged setting goals were associated with less reduction in the frequency of heavy drinking. CONCLUSIONS: Extant alcohol interventions show limited efficacy in reducing consumption and problems among fraternity and sorority members. More robust interventions are needed for use with student members of Greek letter organizations. (PsycINFO Database Record PMID- 27183308 TI - Emotional suppression in chronic fatigue syndrome: Experimental study. AB - OBJECTIVE: Emotional processing differences in chronic fatigue syndrome (CFS) have been reported but have rarely been investigated experimentally. This study used self-report, observer ratings, and electrodermal responses to test hypotheses about emotion suppression and autonomic reactivity. METHODS: Eighty adults with CFS and 80 healthy controls (HC) watched a distressing film clip. Half of each group were instructed to suppress their emotions and half were told to express their feelings as they wished. Their reactions were filmed and rated by independent observers. Electrodermal activity (skin conductance response) was used as a measure of sympathetic nervous system arousal. RESULTS: CFS participants reported higher anxiety and sadness than the HC, both before and after the film. However, observers rated the CFS group as having lower emotional expression than HC in both emotional suppression and expression choice conditions. Beliefs about the unacceptability of negative emotions were associated with greater self-reported suppression. Electrodermal responses were greater in the CFS group than HC participants. Higher skin conductance responses were associated with larger posttask increases in fatigue in the CFS participants but not in the HC. CONCLUSIONS: CFS participants had lower observer-rated emotional expression than HC, despite greater distress and higher autonomic arousal. This may have implications for their ability to access social support at times of stress. As the degree of autonomic arousal was associated with short term increases in fatigue in the CFS participants, this requires further investigation as a contributory factor for this condition. (PsycINFO Database Record PMID- 27183307 TI - Tailoring risk communication to improve comprehension: Do patient preferences help or hurt? AB - OBJECTIVE: Risk communication tools can facilitate patients' understanding of risk information. In this novel study, we examine the hypothesis that risk communication methods tailored to individuals' preferences can increase risk comprehension. METHOD: Preferences for breast cancer risk formats, and risk comprehension data were collected using an online survey from 361 women at high risk for breast cancer. Women's initial preferences were assessed by asking them which of the following risk formats would be the clearest: (a) percentage, (b) frequency, (c) bar graph, (d) pictogram, and (e) comparison to other women. Next, women were presented with 5 different formats for displaying cancer risks and asked to interpret the risk information presented. Finally, they were asked again which risk format they preferred. RESULTS: Initial preferences for risk formats were not associated with risk comprehension scores. However, women with lower risk comprehension scores were more likely to update their risk format preferences after they evaluated risks in different formats. Less numerate women were more likely to prefer graphical rather than numeric risk formats. Importantly, we found that women preferring graphical risk formats had lower risk comprehension in these formats compared to numeric formats. In contrast, women preferring numeric formats performed equally well across formats. CONCLUSIONS: Our findings suggest that tailoring risk communication to patient preferences may not improve understanding of medical risks, particularly for less numerate women, and point to the potential perils of tailoring risk communication formats to patient preferences. (PsycINFO Database Record PMID- 27183309 TI - Influence of Phytoplankton on Fate and Effects of Modified Zerovalent Iron Nanoparticles. AB - Nanoscale zerovalent iron (nZVI) and its derivatives hold promise for remediation of several pollutants but their environmental implications are not completely clear. In this study, the physicochemical properties and aggregation kinetics of sulfide/silica-modified nZVI (FeSSi) were compared in algal media in which Chlamydomonas reinhardtii had been cultured for 1, 2, or 11 days in order to elicit the effects of organic matter produced by the freshwater algae. Furthermore, transformation of FeSSi particles were investigated in C. reinhardtii cultures in exponential (1-d) and slowing growth (11-d) phases while monitoring the response of algae. We found evidence for steric stabilization of FeSSi by algal organic matter, which led to a decrease in the particles' attachment efficiency. Transformation of FeSSi was slower in 11-d cultures as determined via inductively coupled plasma and X-ray analyses. High concentrations of FeSSi caused a lag in algal growth, and reduction in steady state population size, especially in cultures in exponential phase. The different outcomes are well described by a dynamic model describing algal growth, organic carbon production, and FeSSi transformations. This study shows that feedback from algae may play important roles in the environmental implications of engineered nanomaterials. PMID- 27183310 TI - Increased Expression of SETD7 Promotes Cell Proliferation by Regulating Cell Cycle and Indicates Poor Prognosis in Hepatocellular Carcinoma. AB - PURPOSE: To investigate the role of SET domain containing 7 (SETD7) in hepatocellular carcinoma (HCC) and determine whether SETD7 can be used as a predictor of overall survival in HCC patients. METHODS: mRNAs and proteins of SETD7 and related genes in HCC tumor samples and paired adjacent non-tumorous liver tissues (ANLTs) (n = 20) or culture cells were determined by quantitative real-time PCR and Western blot. Cell proliferation and apoptosis with SETD7 knockdown SMMC-7721 cells or SETD7 overexpressed HepG2 cells were analyzed by CCK8 assay or flow cytometry. Gene expression alterations in SETD7 knockdown of SMMC-7721 cells were determined by digital gene expression (DGE) profiling. Defined data on patients (n = 225) with HCC were retrieved for the further study. Tissue microarrays (TMAs) were performed using paraffin tissues with tumor and ANLTs. SETD7 and related proteins were determined by TMAs immunohistochemistry. Statistical analyses were conducted to associate SETD7 expression with tumor features and patient outcomes, as well as related proteins expression. RESULTS: SETD7 expression was significantly higher in HCC tumor tissues than in ANLTs. SETD7 overexpression in vitro can promote HepG2 cell proliferation, whereas SETD7 knockdown can inhibit SMMC-7721 cell proliferation by regulating the cell cycle. SETD7 expression was significantly correlated with five genes expression. Increased SETD7 is associated with metastasis, recurrence, large tumor size, and poor tumor differentiation, and indicates poor prognosis in HCC patients. CONCLUSIONS: SETD7 plays a critical role in HCC, and its immunohistochemistry signature provides potential clinical significance for personalized prediction of HCC prognosis. PMID- 27183311 TI - Association of a New Measure of Obesity with Hypertension and Health-Related Quality of Life. AB - BACKGROUND: Despite its shortcomings, body mass index (BMI) has traditionally been used to define obesity. Another recently introduced obesity measure, A Body Shape Index (ABSI), has been introduced to focus on abdominal obesity, but its applicability remains limited. We analyzed the statistical properties of the ABSI and propose a modified ABSI, the z-score of the log-transformed ABSI (LBSIZ), to improve its applicability. We also examined the sensitivity of the newly introduced index in diagnosing obesity based on the percentage of body fat and its ability to predict hypertension and impaired health-related quality of life (HRQOL). METHODS AND RESULTS: We transformed the ABSI to the LBSIZ in order to create a standard normalized obesity measure. All available data from the Korea National Health and Nutrition Examination Survey (KNHANES) (1998-2012) have shown BMI to be highly correlated with weight (r = 0.85 for women, r = 0.87 for men) and waist circumference (WC) (r = 0.86 for women, r = 0.85 for men), but the LBSIZ was found to be weakly correlated with weight (r = 0.001 for women, r = 0.0001 for men) and moderately correlated with WC (r = 0.51 for women, r = 0.52 for men). BMI showed an inverted U-shaped pattern when plotted against age, but a linear pattern was observed for the LBSIZ, indicating they are different kinds of obesity measures. Logistic regression showed that the odds ratio of obesity for the LBSIZ was 1.86 (95% confidence interval [CI] = 1.73-2.00) for males and 1.32 (95% CI = 1.24-1.40) for females after adjusting for weight, height, age, and year of participation in the KNHANES. While both BMI and the LBSIZ were significantly related to hypertension, the LBSIZ alone was significantly associated with impaired HRQOL. CONCLUSIONS: The LBSIZ is a standard normalized obesity measure independent of weight, height, and BMI. LBSIZ is a new measure of abdominal obesity with the ability to predict hypertension and impaired HRQOL, irrespective of BMI. PMID- 27183313 TI - Politics and population health: Testing the impact of electoral democracy. AB - This study addresses questions of whether and why electoral democracies have better health than other nations. After devising a replicable approach to missing data, we compare political, economic, and health-related data for 168 nations collected annually from 1960 through 2010. Regression models estimate that electoral democracies have 11 years of longer life expectancy on average and 62.5% lower rates of infant mortality. The association with life expectancy reduces markedly after controlling for GDP, while a combination of factors may explain the democratic advantage in infant health. Results suggest that income inequality associates independently with both health outcomes but does not mediate their associations with democracy. PMID- 27183312 TI - Zika Virus as an Emerging Global Pathogen: Neurological Complications of Zika Virus. AB - IMPORTANCE: Zika virus (ZIKV) is an emerging arthropod-borne virus (arbovirus) in the genus Flavivirus that has caused a widespread outbreak of febrile illness, is associated with neurological disease, and has spread across the Pacific to the Americas in a short period. OBSERVATIONS: In this review, we discuss what is currently known about ZIKV, neuroimmunologic complications, and the impact on global human health. Zika virus spread across Africa and Asia in part owing to unique genomic evolutionary conditions and pressures resulting in specific human disease manifestations, complications, and pathogenesis. Recent data suggest that acute ZIKV infection in pregnant women may result in acute infection of fetal tissue and brain tissue, causing microcephaly and potentially severe debilitation of the infant or even death of the fetus. Cases of acute ZIKV are also associated with Guillain-Barre syndrome. With the increased number of cases, new complications such as ocular involvement and sexual transmission have been reported. CONCLUSIONS AND RELEVANCE: Zika virus is an emerging viral pathogen with significant consequences on human health throughout the world. Ongoing research into this pathogen is urgently needed to produce viable vaccine and therapeutic options. PMID- 27183314 TI - Mechanical Behavior of Free-Standing Fuel Cell Electrodes on Water Surface. AB - Fundamental understanding of the mechanical behavior of polymer electrolyte fuel cell electrodes as free-standing materials is essential to develop mechanically robust fuel cells. However, this has been a significant challenge due to critical difficulties, such as separating the pristine electrode from the substrate without damage and precisely measuring the mechanical properties of the very fragile and thin electrodes. We report the mechanical behavior of free-standing fuel cell electrodes on the water surface through adopting an innovative ice assisted separation method to separate the electrode from decal transfer film. It is found that doubling the ionomer content in electrodes increases not only the tensile stress at the break and the Young's modulus (E) of the electrodes by approximately 2.1-3.5 and 1.7-2.4 times, respectively, but also the elongation at the break by approximately 1.5-1.7 times, which indicates that stronger, stiffer, and tougher electrodes are attained with increasing ionomer content, which have been of significant interest in materials research fields. The scaling law relationship between Young's modulus and density (rho) has been unveiled as E ~ rho(1.6), and it is compared with other materials. These findings can be used to develop mechanically robust electrodes for fuel cell applications. PMID- 27183315 TI - Disrupted Leptin Signaling in the Lateral Hypothalamus and Ventral Premammillary Nucleus Alters Insulin and Glucagon Secretion and Protects Against Diet-Induced Obesity. AB - Leptin signaling in the central nervous system, and particularly the arcuate hypothalamic nucleus, is important for regulating energy and glucose homeostasis. However, the roles of extra-arcuate leptin responsive neurons are less defined. In the current study, we generated mice with widespread inactivation of the long leptin receptor isoform in the central nervous system via Synapsin promoter driven Cre (Lepr(flox/flox) Syn-cre mice). Within the hypothalamus, leptin signaling was disrupted in the lateral hypothalamic area (LHA) and ventral premammillary nucleus (PMV) but remained intact in the arcuate hypothalamic nucleus and ventromedial hypothalamic nucleus, dorsomedial hypothalamic nucleus, and nucleus of the tractus solitarius. To investigate the role of LHA/PMV neuronal leptin signaling, we examined glucose and energy homeostasis in Lepr(flox/flox) Syn-cre mice and Lepr(flox/flox) littermates under basal and diet induced obese conditions and tested the role of LHA/PMV neurons in leptin mediated glucose lowering in streptozotocin-induced diabetes. Lepr(flox/flox) Syn cre mice did not have altered body weight or blood glucose levels but were hyperinsulinemic and had enhanced glucagon secretion in response to experimental hypoglycemia. Surprisingly, when placed on a high-fat diet, Lepr(flox/flox) Syn cre mice were protected from weight gain, glucose intolerance, and diet-induced hyperinsulinemia. Peripheral leptin administration lowered blood glucose in streptozotocin-induced diabetic Lepr(flox/flox) Syn-cre mice as effectively as in Lepr(flox/flox) littermate controls. Collectively these findings suggest that leptin signaling in LHA/PMV neurons is not critical for regulating glucose levels but has an indispensable role in the regulation of insulin and glucagon levels and, may promote the development of diet-induced hyperinsulinemia and weight gain. PMID- 27183316 TI - Pharmacological and Genetic Manipulation of p53 in Brown Fat at Adult But Not Embryonic Stages Regulates Thermogenesis and Body Weight in Male Mice. AB - p53 is a well-known tumor suppressor that plays multiple biological roles, including the capacity to modulate metabolism at different levels. However, its metabolic role in brown adipose tissue (BAT) remains largely unknown. Herein we sought to investigate the physiological role of endogenous p53 in BAT and its implication on BAT thermogenic activity and energy balance. To this end, we generated and characterized global p53-null mice and mice lacking p53 specifically in BAT. Additionally we performed gain-and-loss-of-function experiments in the BAT of adult mice using virogenetic and pharmacological approaches. BAT was collected and analyzed by immunohistochemistry, thermography, real-time PCR, and Western blot. p53-deficient mice were resistant to diet induced obesity due to increased energy expenditure and BAT activity. However, the deletion of p53 in BAT using a Myf5-Cre driven p53 knockout did not show any changes in body weight or the expression of thermogenic markers. The acute inhibition of p53 in the BAT of adult mice slightly increased body weight and inhibited BAT thermogenesis, whereas its overexpression in the BAT of diet induced obese mice reduced body weight and increased thermogenesis. On the other hand, pharmacological activation of p53 improves body weight gain due to increased BAT thermogenesis by sympathetic nervous system in obese adult wild type mice but not in p53(-/-) animals. These results reveal that p53 regulates BAT metabolism by coordinating body weight and thermogenesis, but these metabolic actions are tissue specific and also dependent on the developmental stage. PMID- 27183317 TI - Acoustofluidic Transfer of Inflammatory Cells from Human Sputum Samples. AB - For sputum analysis, the transfer of inflammatory cells from liquefied sputum samples to a culture medium or buffer solution is a critical step because it removes the inflammatory cells from the presence of residual dithiothreitol (DTT), a reagent that reduces cell viability and interferes with further sputum analyses. In this work, we report an acoustofluidic platform for transferring inflammatory cells using standing surface acoustic waves (SSAW). In particular, we exploit the acoustic radiation force generated from a SSAW field to actively transfer inflammatory cells from a solution containing residual DTT to a buffer solution. The viability and integrity of the inflammatory cells are maintained during the acoustofluidic-based cell transfer process. Our acoustofluidic technique removes residual DTT generated in sputum liquefaction and facilitates immunophenotyping of major inflammatory cells from sputum samples. It enables cell transfer in a continuous flow, which aids the development of an automated, integrated system for on-chip sputum processing and analysis. PMID- 27183319 TI - Standardized Best Practices and Individual Craft-Based Medicine: A Conversation About Quality. AB - Standardization of medical care through protocols, order sets, and other tools is increasingly a part of efforts to improve quality. The authors, a physician beginning a new position as director of a community hospital quality program and the chief quality officer of a health care system and director of a course in health care delivery improvement, discuss the benefits and risks of standardization in health care. Recommendations for responsible standardization are presented. PMID- 27183320 TI - The forecast model of relationship commitment. AB - Four studies tested the forecast model of relationship commitment, which posits that forecasts of future relationship satisfaction determine relationship commitment and prorelationship behavior in romantic relationships independently of other known predictors and partially explain the effects of these other predictors. This model was supported in 2 cross-sectional studies, a daily report study, and a study using behavioral observation, informant, and longitudinal methods. Across these studies, forecasts of future relationship satisfaction predicted relationship commitment and prorelationship behavior during relationship conflict and partially explained the effects of relationship satisfaction, quality of alternatives, and investment size. These results suggest that representations of the future have a prominent role in interpersonal processes. (PsycINFO Database Record PMID- 27183318 TI - Infrared and Fluorescence Assessment of Protein Dynamics: From Folding to Function. AB - While folding or performing functions, a protein can sample a rich set of conformational space. However, experimentally capturing all of the important motions with sufficient detail to allow a mechanistic description of their dynamics is nontrivial since such conformational events often occur over a wide range of time and length scales. Therefore, many methods have been employed to assess protein conformational dynamics, and depending on the nature of the conformational transition in question, some may be more advantageous than others. Herein, we describe our recent efforts, and also those of others, wherever appropriate, to use infrared- and fluorescence-based techniques to interrogate protein folding and functional dynamics. Specifically, we focus on discussing how to use extrinsic spectroscopic probes to enhance the structural resolution of these techniques and how to exploit various cross-linking strategies to acquire dynamic and mechanistic information that was previously difficult to attain. PMID- 27183321 TI - Aged Garlic Extract Attenuates Neuronal Injury in a Rat Model of Spinal Cord Ischemia/Reperfusion Injury. AB - Garlic has been used as a food as well as a component of traditional medicine. Aged garlic extract (AGE) is claimed to promote human health through antioxidant/anti-inflammatory activities with neuroprotective effects. We evaluated the possible beneficial effect of AGE neurologically, pathologically, ultrastructurally, and biochemically in a spinal cord ischemia-reperfusion (I/R) model of rats. Twenty-four Sprague-Dawley rats were divided into three groups: sham (no I/R), I/R, and AGE (I/R+AGE); each group consisted of eight animals. Animals were evaluated neurologically with the Basso, Beattie, and Bresnahan (BBB) scoring system. The spinal cord tissue samples were harvested for pathological and ultrastructural examinations. Oxidative products (Malondialdehyde, nitric oxide), antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase), inflammatory cytokines (tissue tumor necrosis factor alpha, interleukin-1), and caspase-3 activity were analyzed. The AGE group had significantly higher BBB scores than the I/R group. Pathologically, AGE group revealed reduced degree of ischemia and spinal cord edema. Ultrastructural results also showed preservation of tissue structure in the AGE group. Oxidative product levels of the I/R group were significantly higher than both the other groups, and antioxidant enzyme levels of AGE group were significantly higher than the I/R group. There was also significant difference between the sham and AGE groups in terms of total antioxidant enzyme levels. Furthermore, AGE treatment significantly reduced the inflammatory cytokines and caspase-3 activity than the I/R group. This study demonstrates the considerable neuroprotective effect of AGE on the neurological, pathological, ultrastructural, and biochemical status of rats with I/R-induced spinal cord injury. PMID- 27183322 TI - Nanoscale Chemical Imaging of a Dynamic Molecular Phase Boundary with Ultrahigh Vacuum Tip-Enhanced Raman Spectroscopy. AB - Nanoscale chemical imaging of a dynamic molecular phase boundary has broad implications for a range of problems in catalysis, surface science, and molecular electronics. While scanning probe microscopy (SPM) is commonly used to study molecular phase boundaries, its information content can be severely compromised by surface diffusion, irregular packing, or three-dimensional adsorbate geometry. Here, we demonstrate the simultaneous chemical and structural analysis of N-N' bis(2,6-diisopropylphenyl)-1,7-(4'-t-butylphenoxy)perylene-3,4:9,10 bis(dicarboximide) (PPDI) molecules by UHV tip-enhanced Raman spectroscopy. Both condensed and diffusing domains of PPDI coexist on Ag(100) at room temperature. Through comparison with time-dependent density functional theory simulations, we unravel the orientation of PPDI molecules at the dynamic molecular domain boundary with unprecedented ~4 nm spatial resolution. PMID- 27183323 TI - Introduction to the 2016 Emerging Investigators themed issue. PMID- 27183325 TI - Dental Implants Placed in Periodontally Infected Sites in Humans. AB - BACKGROUND: The purpose of the present study was to evaluate fresh socket implant outcome leaving granulomatous tissue into the bone defects. MATERIALS AND METHODS: Subjects requiring tooth extractions in periodontal infected sites were selected for this prospective study. Only patients with 4-wall defects and asymptomatic ones were included. The fresh sockets were randomly scheduled into two groups: In one group (Removal Group, RG) granulomatous tissue was removed and, in the other group (Left Group, LG) granulomatous tissue was left. Implants were positioned immediately after tooth extraction, and were loaded after 3 months in both groups. Intraoral digital radiographs were performed at temporary prosthesis placement; at 12, 24 and 36 months to evaluate marginal bone levels changes. Moreover, clinical parameters were acquired at the same time points. RESULTS: Sixty patients were included in this study. Three-hundred seventy-two implants were placed immediately after tooth extraction and, at 3-year follow-up, a survival rate of 98.66% was reported, 2 implants were lost in RG and 3 implants in LG. At 36-month follow-up, not statistically significant differences were found between RG and LG in marginal bone level changes and clinical parameters (p > 005). Moreover, not statistically significant differences were found in intragroup comparisons over time (p > 0.05). CONCLUSIONS: With the limits of this study it was concluded that granulomatous tissue left in infected fresh sockets doesn't injury dental implant outcome. PMID- 27183326 TI - An unusual and fatal case of upper gastrointestinal perforation and bleeding secondary to foreign body ingestion. AB - We report a fatal case of gastrointestinal perforation and hemorrhage secondary to the ingestion of a foreign body. While engaged in an amateur futsal competition, an apparently healthy young man suddenly collapsed and his respiration ceased. Autopsy revealed a 3-mm circular perforation on the gastric wall fundus with a significant amount of clotted blood within the gastric lumen. On inspection, a foreign body consisting of a bristle-like hair, later identified via electron microscopy to be a cat vibrissa, i.e. a whisker, was found along the perforation margin. Thus, the inadvertent ingestion of fine, sharp objects (even a cat whisker) can lead to gastric perforation and bleeding, which might prove fatal under given circumstances. PMID- 27183328 TI - Correction to Semi-Experimental Equilibrium Structure Determinations by Employing B3LYP/SNSD Anharmonic Force Fields: Validation and Application to Semirigid Organic Molecules. PMID- 27183327 TI - Exploring the origin of high optical absorption in conjugated polymers. AB - The specific optical absorption of an organic semiconductor is critical to the performance of organic optoelectronic devices. For example, higher light harvesting efficiency can lead to higher photocurrent in solar cells that are limited by sub-optimal electrical transport. Here, we compare over 40 conjugated polymers, and find that many different chemical structures share an apparent maximum in their extinction coefficients. However, a diketopyrrolopyrrole thienothiophene copolymer shows remarkably high optical absorption at relatively low photon energies. By investigating its backbone structure and conformation with measurements and quantum chemical calculations, we find that the high optical absorption can be explained by the high persistence length of the polymer. Accordingly, we demonstrate high absorption in other polymers with high theoretical persistence length. Visible light harvesting may be enhanced in other conjugated polymers through judicious design of the structure. PMID- 27183330 TI - Insights into the control of geminiviral promoters. AB - Geminiviruses constitute one of the largest groups of plant viruses, having characteristic twinned geminate particles encapsidating small circular single stranded DNA molecules. Geminiviral promoters are generally located within the intergenic region, although promoters have also been detected within the genes. Similarly, the geminivirus-associated betasatellite also harbours a promoter element for driving the expression of its only ORF. These regulatory elements of geminiviral and satellite origins have been subject of great interest to develop heterologous gene expression modules. Geminiviral promoter and regulatory elements show a complex regulation that is mediated by several host as well as viral proteins. Here, the structural and functional features of geminiviral and satellite promoters are discussed along with their regulation by plant and viral proteins. Although generalization in many cases is difficult and demands further studies, a pattern is seen to emerge on the regulation of the promoters. PMID- 27183329 TI - SAMHD1 controls cell cycle status, apoptosis and HIV-1 infection in monocytic THP 1 cells. AB - SAMHD1 limits HIV-1 infection in non-dividing myeloid cells by decreasing intracellular dNTP pools. HIV-1 restriction by SAMHD1 in these cells likely prevents activation of antiviral immune responses and modulates viral pathogenesis, thus highlighting a critical role of SAMHD1 in HIV-1 physiopathology. Here, we explored the function of SAMHD1 in regulating cell proliferation, cell cycle progression and apoptosis in monocytic THP-1 cells. Using the CRISPR/Cas9 technology, we generated THP-1 cells with stable SAMHD1 knockout. We found that silencing of SAMHD1 in cycling cells stimulates cell proliferation, redistributes cell cycle population in the G1/G0 phase and reduces apoptosis. These alterations correlated with increased dNTP levels and more efficient HIV-1 infection in dividing SAMHD1 knockout cells relative to control. Our results suggest that SAMHD1, through its dNTPase activity, affects cell proliferation, cell cycle distribution and apoptosis, and emphasize a key role of SAMHD1 in the interplay between cell cycle regulation and HIV-1 infection. PMID- 27183331 TI - Premartensitic transition and relevant magnetic effects in Ni50Mn34In15.5Al0.5 alloy. AB - Resistance measurement, in situ optical microscopic observation, thermal and magnetic measurements have been carried out on Ni50Mn34In15.5Al0.5 alloy. The existence of a pronounced premartensitic transition prior to martensitic transition can be characterized by microstructure evolution as well as exothermic peak and smooth decrease of resistance and magnetization with obvious hysteresis over a wide temperature range upon cooling. Consequently, the alloy undergoes two successive magneto-structural transitions consisting of premartensitic and martensitic transitions. Magnetoelastic coupling between magnetic and structural degrees of freedom would be responsible for the appearance of premartensitic transition, as evinced by the distinct shift of transitions temperatures to lower temperature with external applied field of 50 kOe. The inverse premartensitic transition induced by magnetic field results in large magnetoresistance, and contributes to the enhanced inverse magnetocaloric effect through enlarging the peak value and temperature interval of magnetic entropy change DeltaSm. PMID- 27183332 TI - Surgical challenges in the treatment of a giant renal cell carcinoma with atypical presentation: A case report. AB - INTRODUCTION: For the management of localized renal cell carcinoma (RCC), surgical resection is the standard of care. Considerations are given to achieve good outcomes with conservative measures. When the tumor is exceedingly large the safest alternative is total nephrectomy. PRESENTATION OF CASE: The patient is a 75year old man with a 5year history of increasing abdominal distension. There was no recent hematuria or any other genitourinary complaints. CT revealed a giant complex mass that occupied the majority of the abdomen likely arising from the retroperitoneum. Early in diagnosis, the mass was suspected to arise from the left kidney. The decision was made to proceed with surgery for both treatment and diagnosis. Resection of the tumor revealed a 28.0*25.0*15.0cm encapsulated neoplasm. Histopathology determined this to be a papillary RCC. Resection of the mass resulted in en bloc partial nephrectomy immediately followed by a completion of the nephrectomy, lymphadenectomy, and abdominal wall repair. Postoperative course was excellent. DISCUSSION: The aim of this report is to determine the surgical challenges posed by a tumor of this magnitude and the multidisciplinary approach necessary to treat it. In the often indolent course seen with RCC, surgeons are faced with the task of handling advanced disease, requiring more radical procedures for good outcomes. CONCLUSION: The size of the tumor in this case presented several challenges in the operative setting. The sheer mass of the tumor gave no other choice than to perform exploratory laparotomy and complete nephrectomy upon resection. PMID- 27183333 TI - Synthesis of siderophores by plant-associated metallotolerant bacteria under exposure to Cd(2.). AB - Rhizosphere and endophytic bacteria are well known producers of siderophores, organic compounds that chelate ferric iron (Fe(3+)), and therefore play an important role in plant growth promotion in metalliferous areas, thereby improving bioremediation processes. However, in addition to their primary function in iron mobilization, siderophores also have the capacity to chelate other heavy metals, such as Al(3+), Zn(2+), Cu(2+), Pb(2+) and Cd(2+), that can affect homeostasis and the heavy metal tolerance of microorganisms. The main goal of our study was to select the most efficient siderophore-producing bacterial strains isolated from the roots (endophytes) and rhizosphere of Betula pendula L. and Alnus glutinosa L. growing at two heavy metal contaminated sites in southern Poland. Siderophore biosynthesis of these strains in the presence of increasing concentrations of Cd(2+) (0, 0.5, 1, 2 and 3 mM) under iron-deficiency conditions was analysed using spectrophotometric chemical tests for hydroxamates, catecholates and phenolates, as well as the separation of bacterial siderophores by HPLC and characterization of their structure by UHPLC-QTOF/MS. We proved that (i) siderophore-producing bacterial strains seems to be more abundant in the rhizosphere (47%) than in root endophytes (18%); (ii) the strains most effective at siderophore synthesis belonged to the genus Streptomyces and were able to secrete three types of siderophores under Cd(2+) stress: hydroxamates, catecholates and phenolates; (iii) in general, the addition of Cd(2+) enhanced siderophore synthesis, particularly ferrioxamine B synthesis, which may indicate that siderophores play a significant role in tolerance to Cd(2+) in Streptomyces sp. PMID- 27183334 TI - The oxidative degradation of polystyrene resins on the removal of Cr(VI) from wastewater by anion exchange. AB - Cr(VI) is a powerful oxidant and is capable of oxidizing most of the organic materials. Therefore, it is possible for Cr(VI) to oxidize the polymeric resins and change the sorption properties of the resins on the removal of Cr(VI) from wastewater by anion exchange. In this study, three polystyrene resins (D201, D202, and D301) with different functional groups (-N(+)(CH3)3, N(+)(CH3)2(C2H4OH), and N(CH3)2) were assessed on oxidation stability for Cr(VI) removal from wastewater in fixed-bed column experiments. After a 10-cycle operation, due to the oxidation of the resin, the sorption capacity of D201, D202, and D301 resins decreased by 23.5, 29.3, and 17.3%, when approximately 20 34%, 31-50%, and 18-30% of Cr(VI) was reduced to Cr(III) during each cycle respectively. The results of the Fourier transform infrared spectroscopy (FT-IR) showed that both the cleavage of CN and the formation of CO bonds occurred on the polystyrene resins during the Cr(VI) removal process. The resin simulation experiments further validated the oxidation of CC and CN bonds connected with phenethyl groups. Based upon the results from column operations and the resin simulated experiments, the oxidation mechanism of the polystyrene resin was proposed. PMID- 27183335 TI - Linear and nonlinear models for predicting fish bioconcentration factors for pesticides. AB - This work is devoted to the applications of the multiple linear regression (MLR), multilayer perceptron neural network (MLP NN) and projection pursuit regression (PPR) to quantitative structure-property relationship analysis of bioconcentration factors (BCFs) of pesticides tested on Bluegill (Lepomis macrochirus). Molecular descriptors of a total of 107 pesticides were calculated with the DRAGON Software and selected by inverse enhanced replacement method. Based on the selected DRAGON descriptors, a linear model was built by MLR, nonlinear models were developed using MLP NN and PPR. The robustness of the obtained models was assessed by cross-validation and external validation using test set. Outliers were also examined and deleted to improve predictive power. Comparative results revealed that PPR achieved the most accurate predictions. This study offers useful models and information for BCF prediction, risk assessment, and pesticide formulation. PMID- 27183336 TI - Removal of isopropyl alcohol and methanol in ultrapure water production system using a 185 nm ultraviolet and ion exchange system. AB - The oxidation of low-molecular-weight (LMW) compounds, including isopropyl alcohol (IPA) and methanol in ultrapure water (UPW) production system was evaluated using the continuously operating 185 nm total organic carbon (TOC) reduction UV and ion exchange system. The initial concentration of compounds was in the range of tens of ppb which was the general feed condition of UV system located after 2 pass reverse osmosis (RO) in the UPW production system. UV irradiation transformed the compounds to less oxidative products that were ultimately converted to CO2. The ion exchange system then removed carboxyl containing organic acids generated by UV oxidation. It means that the oxidation efficiency of organic compounds by UV irradiation can be accurately measured by the summation of the final product (CO2) and the by-product containing carboxyl functional group. The removal efficiency of LMW compounds decreased when either the initial TOC concentration increased or the UV intensity was reduced. Finally, the insertion of a baffle into the UV oxidation system was found to enhance solution turbulence and improve the oxidation efficiency. PMID- 27183337 TI - Electrokinetic-Fenton technology for the remediation of hydrocarbons historically polluted sites. AB - The feasibility of the electrokinetic-Fenton technology coupled with surfactants in the treatment of real historically hydrocarbons polluted soils has been studied. The characterisation of these soils from Spain and Romania was performed and identified as diesel and diesel-motor oil spillages, respectively. Moreover, the ageing of the spillages produced by the soil contamination was estimated showing the historical pollution of the sites (around 11 and 20 years for Romanian and Spanish soils, respectively). An ex-situ electrochemical treatment was performed to evaluate the adequacy of surfactants for the degradation of the hydrocarbons present in the soils. It was found an enhancement in the solubilisation and removal of TPHs with percentages increasing from 25.7 to 81.8% by the presence of Tween 80 for Spanish soil and from 15.1% to 71.6% for Triton X100 in Romanian soil. Therefore, the viability of coupling enhanced electrokinetic and Fenton remediation was evaluated through a simulated in-situ treatment at laboratory scale. The results demonstrated that the addition of the selected surfactants improved the solubilisation of the hydrocarbons and influenced the electroosmotic flow with a slight decrease. The efficiency of the treatment increased for both considered soil samples and a significant degradation level of the hydrocarbons compounds was observed. Buffering of pH coupled with the addition of a complexing agent showed to be important in the treatment process, facilitating the conditions for the degradation reactions that take place into the soil matrix. The results demonstrated the effectiveness of the selected techniques for remediation of the investigated soils. PMID- 27183338 TI - Testicular transcript responses in rare minnow Gobiocypris rarus following different concentrations bisphenol A exposure. AB - Bisphenol A (BPA) is widely spread in the environment. It can cause various reproductive disrupting effects on different organisms, including fish. To investigate the effect of BPA at different concentrations comprehensively, RNA seq was performed on the testicular mRNA libraries of adult male rare minnow Gobiocypris rarus that exposed to 0, 1, 15 and 225 MUg/L BPA for 7 days. Meanwhile, biological indicators and sex steroid hormone levels were investigated. Result showed that (1) BPA at all three concentrations affected the expression of genes related to testicular steroid hormone biosynthesis, blood testis barrier, proteolysis, and lipid transport and metabolism. (2) BPA at 1 MUg/L induced gene expression in renin-angiotensin system pathway and possibly initiate membrane form of estrogen receptor (mER); 1 and 15 MUg/L BPA inhibited tRNA processing-related genes expression; 15 and 225 MUg/L BPA decreased hemostasis and blood coagulation-related gene expression. The present study indicated that BPA did influence rare minnow testicular gene expressing, and the effect BPA effects varied with concentration. PMID- 27183339 TI - Microbial degradation of the brominated flame retardant TBNPA by groundwater bacteria: laboratory and field study. AB - In the present study, the biodegradation of the brominated flame retardant tribromoneopentylalcohol (TBNPA) by a groundwater enrichment culture was investigated using a dual carbon ((13)C/(12)C)- bromine ((81)Br/(79)Br) stable isotope analysis. An indigenous aerobic bacterial consortium was enriched from the polluted groundwater underlying an industrial site in the northern Negev Desert, Israel, where TBNPA is an abundant pollutant. Aerobic biodegradation was shown to be rapid, with complete debromination within a few days, whereas anaerobic biodegradation was not observed. Biodegradation under aerobic conditions was accompanied by a significant carbon isotope effect with an isotopic enrichment factor of ECbulk = -8.80/00 +/- 1.50/00, without any detectable bromine isotope fractionation. It was found that molecular oxygen is necessary for biodegradation to occur, suggesting an initial oxidative step. Based on these results, it was proposed that H abstraction from the C-H bond is the first step of TBNPA biodegradation under aerobic conditions, and that the C-H bond cleavage results in the formation of unstable intermediates, which are rapidly debrominated. A preliminary isotopic analysis of TBNPA in the groundwater underlying the industrial area revealed that there are no changes in the carbon and bromine isotope ratio values downstream of the contamination source. Considering that anoxic conditions prevail in the groundwater of the contaminated site, the lack of isotope shifts in TBNPA indicates the lack of TBNPA biodegradation in the groundwater, in accordance with our findings. PMID- 27183340 TI - Screening of the COL2A1 mutation in idiopathic osteonecrosis of the femoral head. AB - Idiopathic osteonecrosis of the femoral head (idiopathic ONFH) is an ischemic disorder resulting in necrosis of the subchondral bone of the femoral head. COL2A1 mutations, including c.3508G>A, have been reported to be involved in its etiology. However, the etiological role of COL2A1 mutations in idiopathic ONFH remains controversial, because the pathology of idiopathic ONFH is ischemic necrosis, not epiphyseal dysplasia usually seen in the diseases caused by COL2A1 mutations. The purpose of this study is to examine whether COL2A1 mutations have causal relation with idiopathic ONFH or not. We recruited 1,451 Japanese patients with idiopathic ONFH, including steroid-, alcohol-, and neither steroid nor alcohol-associated (neither-associated) ONFH. The diagnosis was based on the criteria of the Japanese Research Committee on idiopathic ONFH of the Ministry of Health, Labour and Welfare. By whole-exome sequencing, entire COL2A1 coding regions and flanking introns were analyzed in 49 neither-associated ONFH patients. In addition, the c.3508G>A mutation of COL2A1 was checked in all idiopathic ONFH patients using the invader assay. Whole-exome sequencing did not detect any COL2A1 mutations in the 49 patients. The c.3508G>A mutation was not found in any of the 1,451 patients. In conclusion, COL2A1 is unlikely to cause idiopathic ONFH. Epiphyseal dysplasia of the femoral head caused by COL2A1 mutations may radiographically mimic idiopathic ONFH. COL2A1 mutations should prompt clinical re-evaluation of the patient's phenotype. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:768-774, 2017. PMID- 27183341 TI - Simultaneous anaerobic transformation of tetrachloroethene and carbon tetrachloride in a continuous flow column. AB - Tetrachloroethene (PCE) and carbon tetrachloride (CT) were simultaneously transformed in a packed column that was bioaugmented with the Evanite culture (EV). The data presented here have been obtained over a period of 1930days. Initially the column was continuously fed synthetic groundwater with PCE (0.1mM), sulfate (SO4(2-)) (0.2mM) and formate (2.1mM) or lactate (1.1mM), but not CT. In these early stages of the study the effluent H2 concentrations ranged from 7 to 19nM, and PCE was transformed to ethene (ETH) (81 to 85%) and vinyl chloride (VC) (11 to 17%), and SO4(2-) was completely reduced when using either lactate or formate as electron donors. SO4(2-) reduction occurred concurrently with cis-DCE and VC dehalogenation. Formate was a more effective substrate for promoting dehalogenation based on electron donor utilization efficiency. Simultaneous PCE and CT tests found CT (0.015mM) was completely transformed with 20% observed as chloroform (CF) and trace amounts of chloromethane (CM) and dichloromethane (DCM), but no methane (CH4) or carbon disulfide (CS2). PCE transformation to ETH improved with CT addition in response to increases in H2 concentrations to 160nM that resulted from acetate formation being inhibited by either CT or CF. Lactate fermentation was negatively impacted after CT transformation tests, with propionate accumulating, and H2 concentrations being reduced to below 1nM. Under these conditions both SO4(2-) reduction and dehalogenation were negatively impacted, with sulfate reduction not occurring and PCE being transformed to cis dichloroethene (c-DCE) (52%) and VC (41%). Upon switching to formate, H2 concentrations increased to 40nM, and complete SO4(2-) reduction was achieved, while PCE was transformed to ETH (98%) and VC (1%), with no acetate detected. Throughout the study PCE dehalogenation to ethene was positively correlated with the effluent H2 concentrations. PMID- 27183342 TI - Silver(i) complexes with a P-N hybrid ligand and oxyanions: synthesis, structures, photocatalysis and photocurrent responses. AB - Reactions of a P-N hybrid ligand, N,N-bis(diphenylphosphanylmethyl)-3 aminopyridine (3-bdppmapy), with silver oxysalts including AgNO3, AgOAc, AgBz (Bz = benzoate) and AgSal (Sal = salicylate) under different reaction conditions give rise to seven coordination compounds {[Ag4(MU-eta,eta-NO3)2(MU-eta,eta(2) NO3)2](3-bdppmapy)2}n (1), {[Ag4(MU-eta,eta(2)-NO3)4](3-bdppmapy)2}n (2), {[Ag2(MU-eta(2)-OAc)(MU-eta,eta(2)-OAc)]2(3-bdppmapy)2}n (3), [Ag2(Bz)(MU eta,eta(2)-Bz)(H2O)]2(3-bdppmapy)2 (4), {[Ag4(MU-eta(2)-Bz)2(MU-eta,eta(2) Bz)2](3-bdppmapy)2}n (5), {Ag(Sal)(3-bdppmapy)}n (6) and {[Ag4(Sal)2(MU eta,eta(2)-Sal)2](3-bdppmapy)2}n (7). Single crystal X-ray analyses reveal that 1, 5 and 7 have similar 1D chain structures constructed by [Ag4(MU-eta(2)-Ox)2(MU eta,eta(2)-Ox)2] units (1: Ox(-) = NO3(-); 5: Ox(-) = Bz(-)) or [Ag4(Sal)2(MU eta,eta(2)-Sal)2] units (7) and double 3-bdppmapy bridges. Compound 2 has a 2D layer structure derived from [Ag4(MU-eta,eta(2)-NO3)4] units and single 3 bdppmapy bridges. 3 displays another 2D layer structure formed by [Ag2(MU-eta(2) OAc)(MU-eta,eta(2)-OAc)] units and double 3-bdppmapy bridges. 4 shows a discrete tetranuclear structure formed by two [Ag2(Bz)(eta,eta(2),MU-Bz)(H2O)] units and a pair of 3-bdppmapy bridges, while 6 adopts a 1D chain composed by [AgSal] units and single 3-bdppmapy bridges. 6 and 7 as representative samples display high catalytic activity toward the photodegradation of rhodamine B (RhB) in water. Compound 7 shows a better photocatalytic performance than that of 6, which correlates well with the differences in their anodic photocurrent responses and their HOMO-LUMO energy gaps derived from the density function theory (DFT) calculations. The formation of 6 and 7 from AgSal and 3-bdppmapy provides a new approach to the design and assembly of Ag(i)-supported CPs with interesting structural architectures and higher photocatalytic activity. PMID- 27183355 TI - Ionization Energies, Electron Affinities, and Polarization Energies of Organic Molecular Crystals: Quantitative Estimations from a Polarizable Continuum Model (PCM)-Tuned Range-Separated Density Functional Approach. AB - We propose a new methodology for the first-principles description of the electronic properties relevant for charge transport in organic molecular crystals. This methodology, which is based on the combination of a nonempirical, optimally tuned range-separated hybrid functional with the polarizable continuum model, is applied to a series of eight representative molecular semiconductor crystals. We show that it provides ionization energies, electron affinities, and transport gaps in very good agreement with experimental values, as well as with the results of many-body perturbation theory within the GW approximation at a fraction of the computational costs. Hence, this approach represents an easily applicable and computationally efficient tool to estimate the gas-to-crystal phase shifts of the frontier-orbital quasiparticle energies in organic electronic materials. PMID- 27183357 TI - Crusted scabies in a patient with lepromatous leprosy. PMID- 27183343 TI - Baseline psychophysiological and cortisol reactivity as a predictor of PTSD treatment outcome in virtual reality exposure therapy. AB - Baseline cue-dependent physiological reactivity may serve as an objective measure of posttraumatic stress disorder (PTSD) symptoms. Additionally, prior animal model and psychological studies would suggest that subjects with greatest symptoms at baseline may have the greatest violation of expectancy to danger when undergoing exposure based psychotherapy; thus treatment approaches which enhanced the learning under these conditions would be optimal for those with maximal baseline cue-dependent reactivity. However methods to study this hypothesis objectively are lacking. Virtual reality (VR) methodologies have been successfully employed as an enhanced form of imaginal prolonged exposure therapy for the treatment of PTSD. Our goal was to examine the predictive nature of initial psychophysiological (e.g., startle, skin conductance, heart rate) and stress hormone responses (e.g., cortisol) during presentation of VR-based combat related stimuli on PTSD treatment outcome. Combat veterans with PTSD underwent 6 weeks of VR exposure therapy combined with either d-cycloserine (DCS), alprazolam (ALP), or placebo (PBO). In the DCS group, startle response to VR scenes prior to initiation of treatment accounted for 76% of the variance in CAPS change scores, p < 0.001, in that higher responses predicted greater changes in symptom severity over time. Additionally, baseline cortisol reactivity was inversely associated with treatment response in the ALP group, p = 0.04. We propose that baseline cue activated physiological measures will be sensitive to predicting patients' level of response to exposure therapy, in particular in the presence of enhancement (e.g., DCS). PMID- 27183356 TI - Long-term soy consumption and tumor tissue MicroRNA and gene expression in triple negative breast cancer. AB - BACKGROUND: Soy food intake may have protective effects against the risk for breast cancer, including estrogen receptor (ER)-negative breast cancer. However, the underlying molecular mechanisms remain unclear. METHODS: To evaluate the association of soy intake with the expression of microRNAs (miRNAs) and genes in the tumor tissue of patients with triple-negative breast cancer (TNBC; ie, breast cancer lacking expression of ER, progesterone receptor, and human epidermal growth factor receptor 2), the expression of 800 miRNAs and 302 genes were measured with NanoString nCounter assays in formalin-fixed, paraffin-embedded tumor tissue from 272 TNBC patients. Soy intake during the 1-year period before the cancer diagnosis was assessed with a validated food-frequency questionnaire. The association of soy intake with the expression of miRNAs and genes was evaluated via linear regression analysis with adjustments for patient age and TNM stage. RESULTS: A total of 14 miRNAs and 24 genes were significantly associated with soy food intake (P < .05): Thirteen of the 14 miRNAs (92.9%) and 9 of the 24 genes (37.5%), including tumor suppressors miR-29a-3p and IGF1R, showed overexpression for those women with high soy intake, whereas the remaining miRNAs and genes, including oncogenes KRAS and FGFR4, showed underexpression. Furthermore, cell growth-related genes showed a predominantly underexpression pattern according to a comparison of tumor samples from women with high soy food intake and samples from women with lower soy food intake. CONCLUSIONS: This study suggests that long-term prediagnosis soy intake may lead to increased expression of tumor suppressors and decreased expression of oncogenes, especially cell growth-related genes, in breast tumor tissues. Cancer 2016;122:2544-51. (c) 2016 American Cancer Society. PMID- 27183358 TI - Characterization of the genetic environment of the blaKPC-2 gene among Klebsiella pneumoniae isolates from a Chinese Hospital. AB - Infection caused by carbapenem-resistant Klebsiella pneumoniae has become a major healthcare threat and KPC-2 enzyme is a dominant factor mediating carbapenems resistance in K. pneumoniae. This study was designed to determine the genetic environment of blaKPC-2, which prevailed in clinical K. pneumoniae isolates recovered in Huashan Hospital, Shanghai, China. Forty-two clinical isolates were included in this study by blaKPC-2 screening. After multilocus sequence typing and plasmid analyses of PCR-based replicon typing (PBRT), junction PCR, mapping PCR and crossing PCR assays, primer walking, and amplicon sequencing were used to analyze the genetic environment of the blaKPC-2 gene. ST423, ST65, ST977, and ST11 were all detected in KPC-2-producing K. pneumoniae. Two types of blaKPC-2 bearing genetic structure were found: Tn1721-blaKPC-2-Tn3 and Tn1721-blaKPC-2 DeltaTn3-IS26; and were carried in IncX and IncFII plasmids, respectively. In conclusion, the genetic environment of the blaKPC-2 gene was diverse and Tn1721 blaKPC-2-DeltaTn3-IS26 was dominant in clinical K. pneumoniae isolates in Huashan Hospital. This study sheds some light on the genetic environment and should foster further studies about the mechanism of the blaKPC-2 dissemination. PMID- 27183359 TI - Antimicrobial susceptibility of hospital acquired Stenotrophomonas maltophilia isolate biofilms. AB - AIMS: We sought to characterize the antibiotic susceptibility of strains of Stenotrophomonas maltophilia isolated from clinical samples, and the role of Stenotrophomonas maltophilia biofilm in antibiotic resistance. METHODS: Fifty-one clinical Stenotrophomonas maltophilia isolates were obtained from patients with nosocomial infection in the surgical wards and ICUs of six general hospitals in Tianjin, China. In vitro models of Stenotrophomonas maltophilia biofilms were established and confirmed by scanning electron microscopy and fluorescence microscopy with silver staining. The minimal inhibitory concentrations and biofilm inhibitory concentrations of commonly used antibiotics were determined. RESULTS: 47 of 51 strains were resistant to three or more antibiotics. 42 of 51 strains formed Stenotrophomonas maltophilia biofilms in vitro. Stenotrophomonas maltophilia biofilm formation greatly reduced sensitivity to most tested antibiotics, but not to levofloxacin. However, in the presence of erythromycin scanning electron microscopy revealed that levofloxacin inhibited Stenotrophomonas maltophilia biofilm formation. Factorial ANOVA revealed that erythromycin enhanced susceptibility to levofloxacin, cefoperazone/sulbactam, and piperacillin (p<0.05), and an DeltaE model revealed that levofloxacin and erythromycin acted synergistically in biofilms, suggesting specific use of combined macrolide therapy may represent an effective treatment for Stenotrophomonas maltophilia infection. CONCLUSIONS: Antibiotics could act synergistically to combat the protection conferred to clinical isolates of Stenotrophomonas maltophilia by biofilms. Macrolide antibiotics may be effective where used in combination. PMID- 27183361 TI - Impact of Molecular Orientation and Packing Density on Electronic Polarization in the Bulk and at Surfaces of Organic Semiconductors. AB - The polarizable environment surrounding charge carriers in organic semiconductors impacts the efficiency of the charge transport process. Here, we consider two representative organic semiconductors, tetracene and rubrene, and evaluate their polarization energies in the bulk and at the organic-vacuum interface using a polarizable force field that accounts for induced-dipole and quadrupole interactions. Though both oligoacenes pack in a herringbone motif, the tetraphenyl substituents on the tetracene backbone of rubrene alter greatly the nature of the packing. The resulting change in relative orientations of neighboring molecules is found to reduce the bulk polarization energy of holes in rubrene by some 0.3 eV when compared to tetracene. The consideration of model organic-vacuum interfaces highlights the significant variation in the electrostatic environment for a charge carrier at a surface although the net change in polarization energy is small; interestingly, the environment of a charge even just one layer removed from the surface can be viewed already as representative of the bulk. Overall, it is found that in these herringbone-type layered crystals the polarization energy has a much stronger dependence on the intralayer packing density than interlayer packing density. PMID- 27183360 TI - The use of picosecond lasers beyond tattoos. AB - Picosecond lasers are a novel laser with the ability to create a pulse of less than one nanosecond. They have been available in the clinical context since 2012. Dermatologists are now using picosecond lasers regularly for the treatment of blue and green pigment tattoo removal. This article reviews the use of picosecond lasers beyond tattoo removal. The overall consensus for the use of picosecond lasers beyond tattoo treatment is positive. With examples of this in the treatment of nevus of Ota, minocycline-induced pigmentation, acne scarring, and rhytides. PMID- 27183362 TI - Surgical Workflow Analysis: Ideal Application of Navigated Linear Array Ultrasound in Low-Grade Glioma Surgery. AB - Background Intraoperative imaging in low-grade glioma (LGG) surgery can facilitate residual tumor control and improve surgical outcome. The aim of the study was to evaluate the ideal application and typical interactions of intraoperative MRI (iMRI), conventional low-frequency intraoperative ultrasound (cioUS), and high-frequency linear array intraoperative ultrasound (lioUS) to optimize surgical workflow. Methods Prospectively, we included 11 patients with an LGG. Typical procedural workflow in the iMRI suite was recorded with a compatible software. We took notes of duration, frequency of application, the surgeon's evaluation of image quality, and the respective benefit of lioUS (15 MHz), cioUS (7 MHz), and iMRI (1.5 T). With the help of the workflow software, we meticulously analyzed ~ 55 hours of surgery. Results During the interventions, lioUS was used more often (76.3%) than cioUS (23.7%) and showed a better mean image quality (1 = best to 6 = worst) of 2.08 versus 3.26 with cioUS. The benefit of the lioUS application was rated with an average of 2.27, whereas the cioUS probe only reached a mean value of 3.83. The most common application of lioUS was resection control (42.6%); cioUS was used mainly for orientation (63.2%). Overall, lioUS was used more often and was rated better for both the purposes just described regarding image quality and benefit. Estimated residual tumor based on lioUS alone was lower than the final residual tumor detected with iMRI (7.5% versus 14.5%). The latter technique was rated as the best imaging modality for resection control in all cases followed by lioUS. Conclusion We provide proof of principle for workflow assessment in cranial neurosurgery. Although iMRI remains the imaging method of choice, lioUS has shown to be beneficial in a combined setup. Evaluation of lioUS was significantly superior to cioUS in most indications except for subcortical lesions. PMID- 27183363 TI - An electrochemical immunosensor for quantitative detection of ficolin-3. AB - Diabetes mellitus (DM) is one of the most common metabolic disorders in the world, of which more than 90% is type-2 diabetes mellitus (T2DM). There is a rather urgent need for reliable, sensitive and quick detection techniques in clinical application of T2DM. Ficolin-3 is a potential biomarker of T2DM, because serum ficolin-3 levels are associated with insulin resistance and predict the incidence of T2DM. Herein, a sandwich-type electrochemical immunosensor was developed for the detection of ficolin-3 in human serum. Cyclic voltammetry and the amperometric current versus time were used to characterize the performance of the immunosensor. Under optimal conditions, the detection limitation of ficolin-3 was 100 ng ml(-1) and the linear dynamic range was between 2 and 50 MUg ml(-1). The method has ideal accuracy, excellent stability and selectivity and has wide application prospects in clinical research. PMID- 27183372 TI - Replicability, Reproducibility, and Fragility of Research Findings-Ultimately, Caveat Emptor. PMID- 27183373 TI - Does Preprocedural Ultrasound Increase the First-Pass Success Rate of Epidural Catheterization Before Cesarean Delivery? A Randomized Controlled Trial. AB - BACKGROUND: Preprocedural ultrasound may improve the efficacy and safety of epidural catheterization, especially in difficult cases. Most studies of ultrasound-assisted epidural catheterization in the obstetric population are dated and nonblinded with inconsistent designs. This double-blind, randomized controlled study aimed to compare the ultrasound-assisted with the conventional palpation techniques for epidural catheterization in parturients undergoing cesarean delivery. We hypothesized that the use of preprocedural ultrasound would increase the success rate of epidural catheterization at the first needle pass. METHODS: Eligible subjects were American Society of Anesthesiologists physical status II parturients with full-term singleton pregnancy undergoing elective cesarean delivery using double-interspace combined spinal-epidural anesthesia. Exclusion criteria were age <19 or >40 years, body mass index >=35 kg/m, women presenting in labor or having any contraindication to neuraxial anesthesia, marked spinal deformity, previous spinal surgery, or impalpable anatomical landmarks. One hundred ten patients were randomly allocated into 2 equal groups (palpation and ultrasound groups). All procedures were performed by a single experienced anesthesiologist. Patients and investigators assessing the outcome data were blinded to group allocation. A systematic spinal ultrasound assessment and a sham procedure were performed in the ultrasound and palpation groups, respectively, before attempting epidural catheterization. The primary outcome was the rate of successful epidural catheterization at the first needle pass. Secondary outcomes were the rate of successful epidural catheterization at the first skin puncture, number of performed needle passes and skin punctures, duration of the epidural procedure, patient satisfaction from the procedure, and complications of the procedure (incidence of unintentional dural and vascular punctures, failed block, unilateral or patchy block, and backache). RESULTS: Data from 108 patients (55 patients in the palpation group and 53 patients in the ultrasound group) were analyzed. The rate of successful epidural catheterization at the first needle pass was 60% in the palpation group and 58.5% in the ultrasound group (95% confidence interval of the difference in proportions between groups is -18.5% to 21.6%; P > 0.99). There were no significant differences between the 2 groups in the success rate at the first skin puncture, the number of needle passes and skin punctures, or patient satisfaction. The median (range) duration of the epidural procedure was 185 (57-680) seconds in the ultrasound group and 215 (114-720) seconds in the palpation group (P = 0.036 with the Mann-Whitney U test and P = 0.083 with the Student t test with unequal variances). The overall rate of complications of the procedure was low in both groups. CONCLUSIONS: For experienced anesthesiologists, it remains unclear whether preprocedural ultrasound improves the epidural catheterization technique in parturients with palpable anatomical landmarks undergoing cesarean delivery. PMID- 27183374 TI - Continuing the Terra Firma and Establishing a New EQUATOR for Anesthesia & Analgesia. PMID- 27183375 TI - Advanced Uses of Pulse Oximetry for Monitoring Mechanically Ventilated Patients. AB - Pulse oximetry is an undisputable standard of care in clinical monitoring. It combines a spectrometer to detect hypoxemia with a plethysmograph for the diagnosis, monitoring, and follow-up of cardiovascular diseases. These pulse oximetry capabilities are extremely useful for assessing the respiratory and circulatory status and for monitoring of mechanically ventilated patients. On the one hand, the key spectrography-derived function of pulse oximetry is to evaluate a patient's gas exchange that results from a particular ventilatory treatment by continuously and noninvasively measuring arterial hemoglobin saturation (SpO2). This information helps to maintain patients above the hypoxemic levels, leading to appropriate ventilator settings and inspired oxygen fractions. However, whenever higher than normal oxygen fractions are used, SpO2 can mask existing oxygenation defects in ventilated patients. This limitation, resulting from the S shape of the oxyhemoglobin saturation curve, can be overcome by reducing the oxygen fraction delivered to the patient in a controlled and stepwise manner. This results in a SpO2/FIO2 diagram, which allows a rough characterization of a patient's gas exchange, shunt, and the amount of lung area with a low ventilation/perfusion ratio without the need of blood sampling. On the other hand, the photoplethysmography-derived oximeter function has barely been exploited for the purpose of monitoring hemodynamics in mechanically ventilated patients. The analysis of the photoplethysmography contour provides useful real time and noninvasive information about the interaction of heart and lungs during positive pressure ventilation. These hemodynamic monitoring capabilities are related to both the assessment of preload dependency-mainly by analyzing the breath-by-breath variation of the photoplethysmographic signals-and the analysis of arterial impedance, which examines the changes in the plethysmographic amplitude, contour, and derived indexes. In this article, we present and describe these extended monitoring capabilities and propose a more holistic monitoring concept that takes advantage of these advanced uses of pulse oximetry in the monitoring of ventilated patients. Today's monitors need to be improved if such novel functionalities were to be offered for clinical use. Future developments and clinical evaluations are needed to establish the true potential of these advanced monitoring uses of pulse oximetry. PMID- 27183376 TI - Tos-Nos-Mos: Synthesis of different aryl sulfonate precursors for the radiosynthesis of the alpha7 nicotinic acetylcholine receptor radioligand [(18)F]NS14490. AB - Radiopharmacological investigations of [(18)F]NS14490 have proven that this radiotracer could be a potential PET radiotracer for imaging of alpha7 nicotinic acetylcholine receptor particularly with regard to vulnerable plaques of diseased vessels. For further optimisation of the previously automated one-pot radiosynthesis of [(18)F]NS14490 using a tosylate precursor, precursors with other leaving groups (nosylate and mosylate) were synthesized and compared with the tosylate with respect to their reactivities towards [(18)F]fluoride. The use of these different precursors resulted in comparable labelling yields of [(18)F]NS14490. A novel mosylate precursor was synthesized and evaluated, which has revealed a higher stability during a storage period of five months compared to the corresponding tosylate and nosylate. PMID- 27183377 TI - Hydroxychloroquine augments early virological response to pegylated interferon plus ribavirin in genotype-4 chronic hepatitis C patients. AB - The therapeutic effect of pegylated interferon (peg-IFN) alfa-2a combined with ribavirin (RBV) on chronic hepatitis C Egyptian patients is low and further efforts are required to optimize this therapy for achievement of higher rates of virological response. This study aimed to evaluate the safety and efficacy of hydroxychloroquine (HCQ) in combination with pegylated interferon plus ribavirin on early virological response (EVR) in chronic hepatitis C Egyptian patients. Naive 120 Egyptian patients with chronic hepatitis C virus infection were divided into two groups. Group 1 have administered the standard of care therapy (pegylated interferon alfa-2a plus ribavirin) for 12 weeks, (n = 60). Group 2 have administered hydroxychloroquine plus standard of care therapy for 12 weeks, (n = 60). Therapeutics included hydroxychloroquine (200 mg) oral twice daily, peginterferon alfa-2a (160 MUg) subcutaneous once weekly and oral weight-based ribavirin (1000-1200 mg/day). Baseline characteristics were similar in the two groups. The percentage of early virological response was significantly more in patients given the triple therapy than in patients given the standard of care [54/60 (90%) vs. 43/60 (71.7%); P = 0.011; respectively]. Biochemical response at week 12 was also significantly higher in patients given the triple therapy compared with the standard of care [58/60 (96.7%) vs. 42/60 (70%); P < 0.001; respectively]. Along the study, the observed adverse events were mild and similar across treatment groups. Addition of hydroxychloroquine to pegylated interferon plus ribavirin improves the rate of early virological and biochemical responses in chronic hepatitis C Egyptian patients without an increase in adverse events. J. Med. Virol. 88:2170-2178, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27183378 TI - Detection of blaOXA-23-like and blaNDM-1 in Acinetobacter baumannii from the Eastern Region, Saudi Arabia. AB - Acinetobacter baumannii is currently considered as one of the most common successful pathogens in the healthcare system due to its ability to quickly develop resistance. Ten carbapenem-resistant A. calcoaceticus-baumannii complex were isolated from the eastern region, Saudi Arabia in 2014. All isolates were resistant to ciprofloxacin, however, 8 of 10 isolates were tigecycline resistant. Susceptibility test was also carried out for three aminoglycosides, resistance to gentamicin was 80%, amikacin was 90%, and tobramycin was 50%. Colistin susceptibility was seen in all isolates. The 10 isolates harbored blaOXA-23-like and ISAba1 and 9 of them also carried blaADC. Three isolates of 10 harbored blaNDM-1 coding for NDM metallo-beta-lactamase (MBL) with coexistence of blaADC together with either blaGES or blaTEM or both. Those three isolates exhibited negative Etest MBL screening test. Pulsed-field gel electrophoresis revealed the high clonal variability of the isolates, although two isolates were indistinguishable. The risk of dissemination of carbapenem resistance through presence of ISAba1 upstream of OXA-23-like in all isolates raises the concern about emergence of higher carbapenem prevalence rates in the future in our region. This study also demonstrated the importance of molecular surveillance to provide accurate and reliable data about the resistance rates of A. baumannii. Finally, the high incidence of NDM-1 among our isolates requires a routine surveillance to monitor the future prevalence of this enzyme in the region. PMID- 27183380 TI - A t(17;19)(q22;p13.3) Involving TCF3, a t(1;9)(p13;p13), and a 5' IGH Deletion in a Case of Adult B-cell Acute Lymphoblastic Leukemia. AB - TCF3 (19p13.3) abnormalities are relatively common in B-cell acute lymphoblastic leukemia (B-ALL). The t(1;19)(q23;p13) involving PBX1 is the most common of these rearrangements. The t(17;19)(q22;p13.3), resulting in the TCF3-HLF fusion gene, is also seen in B-ALL and is associated with an extremely poor prognosis. Herein, we present the case of a 25-year-old male diagnosed with B-ALL whose initial karyotype showed a t(17;19)(q22p13.3). FISH confirmed TCF3 involvement and also revealed a 5' IGH deletion. After treatment, the patient relapsed, at which point conventional cytogenetic studies showed a t(17;19), loss of the 5' IGH region, and a t(3;10) not seen in initial studies. After hematopoietic stem cell transplantation, the patient relapsed again, at which point conventional cytogenetic studies showed a complex karyotype with t(17;19), t(1;9)(p13;p13), and structural anomalies involving chromosomes 5, 7, and 14, but no IGH abnormalities by FISH. The t(1;9) has been shown to involve PAX5, which plays numerous regulatory roles in B-cell differentiation. Other PAX5 rearrangements have been detected in B-ALL cases of young adults and adolescents, but with unclear clinical significance. To the best of our knowledge, this is the first reported case of t(17;19)-ALL with concomitant 5' IGH deletion and t(1;9)(p13;p13) potentially involving PAX5, albeit at different time points in disease progression. This case provides insight into the clonal evolution of t(17;19)-ALL and the potential involvement of PAX5 and IGH aberrations in the evolution of this malignancy. PMID- 27183379 TI - New insight into the structural, electrochemical and biological aspects of macroacyclic Cu(II) complexes derived from S-substituted dithiocarbazate schiff bases. AB - Copper (II) complexes synthesized from the products of condensation of S-methyl- and S-benzyldithiocarbazate with 2,5-hexanedione (SMHDH2 and SBHDH2 respectively) have been characterized using various physicochemical (elemental analysis, molar conductivity, magnetic susceptibility) and spectroscopic (infrared, electronic) methods. The structures of SMHDH2, its copper (II) complex, CuSMHD, and the related CuSBHD complex as well as a pyrrole byproduct, SBPY, have been determined by single crystal X-ray diffraction. In order to provide more insight into the behaviour of the complexes in solution, electron paramagnetic resonance (EPR) and electrochemical experiments were performed. Antibacterial activity and cytotoxicity were evaluated. The compounds, dissolved in 0.5% and 5% DMSO, showed a wide range of antibacterial activity against 10 strains of Gram-positive and Gram-negative bacteria. Investigations of the effects of efflux pumps and membrane penetration on antibacterial activity are reported herein. Antiproliferation activity was observed to be enhanced by complexation with copper. Preliminary screening showed Cu complexes are strongly active against human breast adenocarcinoma cancer cell lines MDA-MB-231 and MCF-7. PMID- 27183381 TI - Extracellular vesicles: interneural shuttles of complex messages. AB - A core function of neural cells is the exchange and integration of information. Extracellular vesicles such as exosomes and microvesicles recently entered the scene of neuroscience as novel vehicles transmitting complex signals between neural cells. Carrying a defined but mixed cargo of biomolecules, extracellular vesicles possess versatile biological activities with the ability to profoundly modulate the molecular configuration and behaviour of target cells. Extracellular vesicles are suggested to carry out functions during neural development and maintenance, they appear to spread neuropathology and furthermore, convey neuroprotection and regeneration. Understanding the molecular mechanisms of this sophisticated cellular crosstalk will fundamentally improve our insight in complex intercellular processes in the healthy and diseased nervous system. PMID- 27183382 TI - Incentivizing Decentralized Sanitation: The Role of Discount Rates. AB - In adoption decisions for decentralized sanitation technologies, two decision makers are involved: the public utility and the individual homeowner. Standard life cycle cost is calculated from the perspective of the utility, which uses a market-based discount rate in these calculations. However, both decision-makers must be considered, including their differing perceptions of the time trade-offs inherent in a stream of costs and benefits. This study uses the discount rate as a proxy for these perceptions and decision-maker preferences. The results in two case studies emphasize the dependence on location of such analyses. Falmouth, Massachusetts, appears to be a good candidate for incentivizing decentralized sanitation while the Allegheny County Sanitary Authority service area in Pennsylvania appears to have no need for similar incentives. This method can be applied to any two-party decision in which the parties are expected to have different discount rates. PMID- 27183384 TI - Vision of correction for classic homocystinuria. AB - Inherited metabolic disorders are often characterized by the lack of an essential enzyme and are currently treated by dietary restriction and other strategies to replace the substrates or products of the missing enzyme. Patients with homocystinuria lack the enzyme cystathionine beta-synthase (CBS), and many of these individuals do not respond to current treatment protocols. In this issue of the JCI, Bublil and colleagues demonstrate that enzyme replacement therapy (ERT) provides long-term amelioration of homocystinuria-associated phenotypes in CBS deficient murine models. A PEGylated form of CBS provided long-term stability and, when used in conjunction with the methylation agent betaine, dramatically increased survival in mice fed a normal diet. The results of this study provide one of the first examples of ERT for a metabolic disorder and suggest that PEGylated CBS should be further explored for use in patients. PMID- 27183383 TI - Stabilization of histone demethylase PHF8 by USP7 promotes breast carcinogenesis. AB - The histone demethylase PHF8 has been implicated in multiple pathological disorders, including X-linked mental retardation and tumorigenesis. However, it is not clear how the abundance and function of PHF8 are regulated. Here, we report that PHF8 physically associates with the deubiquitinase USP7. Specifically, we demonstrated that USP7 promotes deubiquitination and stabilization of PHF8, leading to the upregulation of a group of genes, including cyclin A2, that are critical for cell growth and proliferation. The USP7-encoding gene was also transcriptionally regulated by PHF8, via positive feedback. USP7 was overexpressed in breast carcinomas, and the level of expression positively correlated with expression of PHF8 and cyclin A2 and with the histological grade of breast cancer. We showed that USP7 promotes breast carcinogenesis by stabilizing PHF8 and upregulating cyclin A2 and that the interaction between USP7 and PHF8 is augmented during DNA damage. Moreover, USP7-promoted PHF8 stabilization conferred cellular resistance to genotoxic insults and was required for the recruitment of BLM and KU70, which are both essential for DNA double strand break repair. Our study mechanistically links USP7 to epigenetic regulation and DNA repair. Moreover, these data support the pursuit of USP7 and PHF8 as potential targets for breast cancer intervention, especially in combination with chemo- or radiotherapies. PMID- 27183385 TI - Enzyme replacement with PEGylated cystathionine beta-synthase ameliorates homocystinuria in murine model. AB - Homocystinuria, which typically results from cystathionine beta-synthase (CBS) deficiency, is the most common defect of sulfur amino acid metabolism. CBS condenses homocysteine and serine to cystathionine that is then converted to cysteine. Individuals with homocystinuria have markedly elevated plasma levels of homocysteine and methionine and reduced concentrations of cystathionine and cysteine. Clinical disease manifestations include thromboembolism and neuropsychiatric, ocular, and skeletal complications. Here, we have shown that administration of PEGylated CBS into the circulation of homocystinuria model mice alters the extra- and intracellular equilibrium of sulfur amino acids, resulting in a decrease of approximately 75% in plasma total homocysteine (tHcy) and normalization of cysteine concentrations. Moreover, the decrease in homocysteine and the normalization of cysteine in PEGylated CBS-treated model mice were accompanied by improvement of histopathological liver symptoms and increased survival. Together, these data suggest that CBS enzyme replacement therapy (ERT) is a promising approach for the treatment of homocystinuria and that ERT for metabolic diseases may not necessitate introduction of the deficient enzyme into its natural intracellular compartment. PMID- 27183386 TI - A "hotspot" for autoimmune T cells in type 1 diabetes. AB - The ability of a single T cell antigen receptor (TCR) to cross-react with multiple antigens allows the finite number of T cells within an organism to respond to the compendium of pathogen challenges faced during a lifetime. Effective immune surveillance, however, comes at a price. TCR cross-reactivity can allow molecular mimics to spuriously activate autoimmune T cells; it also underlies T cell rejection of organ transplants and drives graft-versus-host disease. In this issue of the JCI, Cole and colleagues provide insight into how an insulin-reactive T cell cross-reacts with pathogen-derived antigens by focusing on a limited portion of the peptides to provide a hotspot for binding. These findings dovetail with recent studies of alloreactive and autoimmune TCRs and suggest that the biochemical principles that govern conventional protein protein interactions may allow the specificity and cross-reactivity profiles of T cells to be predicted. PMID- 27183387 TI - Inhibition of SHP2 ameliorates the pathogenesis of systemic lupus erythematosus. AB - Systemic lupus erythematosus (SLE) is a devastating multisystemic autoimmune disorder. However, the molecular mechanisms underlying its pathogenesis remain elusive. Some patients with Noonan syndrome, a congenital disorder predominantly caused by gain-of-function mutations in the protein tyrosine phosphatase SH2 domain-containing PTP (SHP2), have been shown to develop SLE, suggesting a functional correlation between phosphatase activity and systemic autoimmunity. To test this directly, we measured SHP2 activity in spleen lysates isolated from lupus-prone MRL/lpr mice and found it was markedly increased compared with that in control mice. Similar increases in SHP2 activity were seen in peripheral blood mononuclear cells isolated from lupus patients relative to healthy patients. To determine whether SHP2 alters autoimmunity and related immunopathology, we treated MRL/lpr mice with an SHP2 inhibitor and found increased life span, suppressed crescentic glomerulonephritis, reduced spleen size, and diminished skin lesions. SHP2 inhibition also reduced numbers of double-negative T cells, normalized ERK/MAPK signaling, and decreased production of IFN-gamma and IL 17A/F, 2 cytokines involved in SLE-associated organ damage. Moreover, in cultured human lupus T cells, SHP2 inhibition reduced proliferation and decreased production of IFN-gamma and IL-17A/F, further implicating SHP2 in lupus associated immunopathology. Taken together, these data identify SHP2 as a critical regulator of SLE pathogenesis and suggest targeting of its activity as a potent treatment for lupus patients. PMID- 27183388 TI - CD62L+ NKT cells have prolonged persistence and antitumor activity in vivo. AB - Valpha24-invariant natural killer T cells (NKTs) localize to tumors and have inherent antitumor properties, making them attractive chimeric antigen receptor (CAR) carriers for redirected cancer immunotherapy. However, clinical application of CAR-NKTs has been impeded, as mechanisms responsible for NKT expansion and the in vivo persistence of these cells are unknown. Here, we demonstrated that antigen-induced expansion of primary NKTs in vitro associates with the accumulation of a CD62L+ subset and exhaustion of CD62L- cells. Only CD62L+ NKTs survived and proliferated in response to secondary stimulation. When transferred to immune-deficient NSG mice, CD62L+ NKTs persisted 5 times longer than CD62L- NKTs. Moreover, CD62L+ cells transduced with a CD19-specific CAR achieved sustained tumor regression in a B cell lymphoma model. Proliferating CD62L+ cells downregulated or maintained CD62L expression when activated via T cell receptor alone or in combination with costimulatory receptors. We generated HLAnull K562 cell clones that were engineered to express CD1d and costimulatory ligands. Clone B-8-2 (HLAnullCD1dmedCD86high4-1BBLmedOX40Lhigh) induced the highest rates of NKT expansion and CD62L expression. B-8-2-expanded CAR-NKTs exhibited prolonged in vivo persistence and superior therapeutic activities in models of lymphoma and neuroblastoma. Therefore, we have identified CD62L as a marker of a distinct NKT subset endowed with high proliferative potential and have developed artificial antigen-presenting cells that generate CD62L-enriched NKTs for effective cancer immunotherapy. PMID- 27183390 TI - Epithelial tethering of MUC5AC-rich mucus impairs mucociliary transport in asthma. AB - The development of pathologic mucus, which is not readily cleared from the airways, is an important contributor to the morbidity and mortality associated with asthma. It is not clear how the major airway mucins MUC5AC and MUC5B are organized within the mucus gel or how this gel contributes to airway obstruction in asthma. Here, we demonstrated that mucus plugs from individuals with fatal asthma are heterogeneous gels with distinct MUC5AC- and MUC5B-containing domains. Stimulation of cultured human bronchial epithelial cells with IL-13, a key mediator in asthma, induced the formation of heterogeneous mucus gels and dramatically impaired mucociliary transport. Impaired transport was not associated with defects in ciliary function but instead was related to tethering of MUC5AC-containing mucus gel domains to mucus-producing cells in the epithelium. Replacement of tethered mucus with untethered mucus restored mucociliary transport. Together, our results indicate that tethering of MUC5AC containing domains to the epithelium causes mucostasis and likely represents a major cause of mucus plugging in asthma. PMID- 27183389 TI - Hotspot autoimmune T cell receptor binding underlies pathogen and insulin peptide cross-reactivity. AB - The cross-reactivity of T cells with pathogen- and self-derived peptides has been implicated as a pathway involved in the development of autoimmunity. However, the mechanisms that allow the clonal T cell antigen receptor (TCR) to functionally engage multiple peptide-major histocompatibility complexes (pMHC) are unclear. Here, we studied multiligand discrimination by a human, preproinsulin reactive, MHC class-I-restricted CD8+ T cell clone (1E6) that can recognize over 1 million different peptides. We generated high-resolution structures of the 1E6 TCR bound to 7 altered peptide ligands, including a pathogen-derived peptide that was an order of magnitude more potent than the natural self-peptide. Evaluation of these structures demonstrated that binding was stabilized through a conserved lock-and key-like minimal binding footprint that enables 1E6 TCR to tolerate vast numbers of substitutions outside of this so-called hotspot. Highly potent antigens of the 1E6 TCR engaged with a strong antipathogen-like binding affinity; this engagement was governed though an energetic switch from an enthalpically to entropically driven interaction compared with the natural autoimmune ligand. Together, these data highlight how T cell cross-reactivity with pathogen-derived antigens might break self-tolerance to induce autoimmune disease. PMID- 27183392 TI - Deconstructing Planning Ability in Children and Adolescents with Anorexia Nervosa. AB - Weaknesses in planning by patients with anorexia nervosa (AN) have been noted (e.g., Zakzanis, Campbell, & Polsinelli, 2010 ) and are generally based on adults. This study explored D-KEFS Tower Test performance to better understand learning styles and strategies used by child and adolescent patients with AN compared to healthy controls. Overall, no significant differences were found in achievement; however, Item 5 predicted performance across harder items. The AN group was significantly faster to move their first disc suggesting patients with AN did not spend as much time planning their strategies for item completion. The findings of this study in conjunction with other studies investigating planning in AN may suggest the existence of subtle differences in learning style and strategy, such as faster initiation times, rather than gross planning differences. Further research is required to better understand the relationship between these subtle differences and clinical presentations. PMID- 27183391 TI - Oxidative stress and dysfunctional NRF2 underlie pachyonychia congenita phenotypes. AB - Palmoplantar keratoderma (PPK) are debilitating lesions that arise in individuals with pachyonychia congenita (PC) and feature upregulation of danger-associated molecular patterns and skin barrier regulators. The defining features of PC associated PPK are reproduced in mice null for keratin 16 (Krt16), which is commonly mutated in PC patients. Here, we have shown that PPK onset is preceded by oxidative stress in footpad skin of Krt16-/- mice and correlates with an inability of keratinocytes to sustain nuclear factor erythroid-derived 2 related factor 2-dependent (NRF2-dependent) synthesis of the cellular antioxidant glutathione (GSH). Additionally, examination of plantar skin biopsies from individuals with PC confirmed the presence of high levels of hypophosphorylated NRF2 in lesional tissue. In Krt16-/- mice, genetic ablation of Nrf2 worsened spontaneous skin lesions and accelerated PPK development in footpad skin. Hypoactivity of NRF2 in Krt16-/- footpad skin correlated with decreased levels or activity of upstream NRF2 activators, including PKCdelta, receptor for activated C kinase 1 (RACK1), and p21. Topical application of the NRF2 activator sulforaphane to the footpad of Krt16-/- mice prevented the development of PPK and normalized redox balance via regeneration of GSH from existing cellular pools. Together, these findings point to oxidative stress and dysfunctional NRF2 as contributors to PPK pathogenesis, identify K16 as a regulator of NRF2 activation, and suggest that pharmacological activation of NRF2 should be further explored for PC treatment. PMID- 27183393 TI - Swelling of Bicontinuous Cubic Phases in Guerbet Glycolipid: Effects of Additives. AB - Inverse bicontinuous cubic phases of lyotropic liquid crystal self-assembly have received much attention in biomedical, biosensing, and nanotechnology applications. An Ia3d bicontinuous cubic based on the gyroid G-surface can be formed by the Guerbet synthetic glucolipid 2-hexyl-decyl-beta-d-glucopyranoside (beta-Glc-OC6C10) in excess water. The small water channel diameter of this cubic phase could provide nanoscale constraints in encapsulation of large molecules and crystallization of membrane proteins, hence stresses the importance of water channel tuning ability. This work investigates the swelling behavior of lyotropic self-assembly of beta-Glc-OC6C10 which could be controlled and modulated by different surfactants as a hydration-modulating agent. Our results demonstrate that addition of nonionic glycolipid octyl-beta-d-glucopyranoside (beta-Glc-OC8) at 20 and 25 mol % gives the largest attainable cubic water channel diameter of ca. 62 A, and formation of coacervates which may be attributed to a sponge phase were seen at 20 mol % octyl-beta-d-maltopyranoside (beta-Mal-OC8). Swelling of the cubic water channel can also be attained in charged surfactant-doped systems dioctyl sodium sulfosuccinate (AOT) and hexadecyltrimethylammonium bromide (CTAB), of which phase transition occurred from cubic to a lamellar phase. Destabilization of the cubic phase to an inverse hexagonal phase was observed when a high amount of charged lecithin (LEC) and stearylamine (SA) was added to the lipid self-assembly. PMID- 27183394 TI - Trauma Sequelae are Uniquely Associated with Components of Self-Reported Sleep Dysfunction in OEF/OIF/OND Veterans. AB - While the associations between psychological distress (e.g., posttraumatic stress disorder [PTSD], depression) and sleep dysfunction have been demonstrated in trauma-exposed populations, studies have not fully explored the associations between sleep dysfunction and the wide range of common physical and physiological changes that can occur after trauma exposure (e.g., pain, cardiometabolic risk factors). We aimed to clarify the unique associations of psychological and physical trauma sequelae with different aspects of self-reported sleep dysfunction. A comprehensive psychological and physical examination was administered to 283 combat-deployed trauma-exposed Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND) veterans. The Pittsburgh Sleep Quality Index (PSQI) and PSQI Addendum for PSTD (PSQI-A) were administered along with measures of PTSD, depression, anxiety, pain, traumatic brain injury, alcohol use, nicotine dependence, and cardiometabolic symptoms. We first performed a confirmatory factor analysis of the PSQI and then conducted regressions with the separate PSQI factors as well as the PSQI-A to identify unique associations between trauma-related measures and the separate aspects of sleep. We found that the PSQI global score was composed of three factors: Sleep Efficiency (sleep efficiency/sleep duration), Perceived Sleep Quality (sleep quality/sleep latency/sleep medication) and Daily Disturbances (sleep disturbances/daytime dysfunction). Linear regressions demonstrated that PTSD symptoms were uniquely associated with the PSQI global score and all three factors, as well as the PSQI-A. For the other psychological distress variables, anxiety was independently associated with PSQI global as well as Sleep Efficiency, Perceived Sleep Quality, and PSQI-A, whereas depression was uniquely associated with Daily Disturbances and PSQI-A. Notably, cardiometabolic symptoms explained independent variance in PSQI global and Sleep Efficiency. These findings help lay the groundwork for further investigations of the mechanisms of sleep dysfunction in trauma-exposed individuals and may help in the development of more effective, individualized treatments. PMID- 27183395 TI - The Promise of Leisure-Time Physical Activity to Reduce Risk of Cancer Development. PMID- 27183396 TI - Immunomodulation with Self-Crosslinked Polyelectrolyte Multilayer-Based Coatings. AB - This study aims to design an optimal polyelectrolyte multilayer film of poly-l lysine (PLL) and hyaluronic acid (HA) as an anti-inflammatory cytokine release system in order to decrease the implant failure due to any immune reactions. The chemical modification of the HA with aldehyde moieties allows self-cross-linking of the film and an improvement in the mechanical properties of the film. The cross-linking of the film and the release of immunomodulatory cytokine (IL-4) stimulate the differentiation of primary human monocytes seeded on the films into pro-healing macrophages phenotype. This induces the production of anti inflammatory cytokines (IL1-RA and CCL18) and the decrease of pro-inflammatory cytokines secreted (IL-12, TNF-alpha, and IL-1beta). Moreover, we demonstrate that cross-linking PLL/HA film using HA-aldehyde is already effective by itself to limit inflammatory processes. Finally, this functionalized self-cross-linked PLL/HA-aldehyde films constitutes an innovative and efficient candidate for immunomodulation of any kind of implants of various architecture and properties. PMID- 27183398 TI - The role of shared visual information for joint action coordination. AB - Previous research has identified a number of coordination processes that enable people to perform joint actions. But what determines which coordination processes joint action partners rely on in a given situation? The present study tested whether varying the shared visual information available to co-actors can trigger a shift in coordination processes. Pairs of participants performed a movement task that required them to synchronously arrive at a target from separate starting locations. When participants in a pair received only auditory feedback about the time their partner reached the target they held their movement duration constant to facilitate coordination. When they received additional visual information about each other's movements they switched to a fundamentally different coordination process, exaggerating the curvature of their movements to communicate their arrival time. These findings indicate that the availability of shared perceptual information is a major factor in determining how individuals coordinate their actions to obtain joint outcomes. PMID- 27183399 TI - Lexical distributional cues, but not situational cues, are readily used to learn abstract locative verb-structure associations. AB - Children must learn the structural biases of locative verbs in order to avoid making overgeneralisation errors (e.g., (*)I filled water into the glass). It is thought that they use linguistic and situational information to learn verb classes that encode structural biases. In addition to situational cues, we examined whether children and adults could use the lexical distribution of nouns in the post-verbal noun phrase of transitive utterances to assign novel verbs to locative classes. In Experiment 1, children and adults used lexical distributional cues to assign verb classes, but were unable to use situational cues appropriately. In Experiment 2, adults generalised distributionally-learned classes to novel verb arguments, demonstrating that distributional information can cue abstract verb classes. Taken together, these studies show that human language learners can use a lexical distributional mechanism that is similar to that used by computational linguistic systems that use large unlabelled corpora to learn verb meaning. PMID- 27183397 TI - Try to see it my way: Embodied perspective enhances self and friend-biases in perceptual matching. AB - Four experiments tested whether self- and friend-biases in perceptual matching are modulated by whether stimuli are presented aligned with the participant's body and seen from the same perspective (the embodied perspective). Participants associated three colours (blue, green, and red) with three people (self, friend, and stranger) and then judged if a pairing of a colour and a personal label matched. The colour was painted on the T-shirt of an avatar. We modulated the perspective of the avatar along with its alignment with the participant's body. In Experiment 1 a single avatar appeared. In Experiments 2-4 there were two avatars, and we varied the social communicative environment between the two avatars (social vs. non-social in Experiments 2/4 vs. 3) and the distance between the two avatars and fixation (close, far, or equal in Experiment 2, 3 or 4). With a single avatar, performance on friend-match trials selectively improved when the avatar was aligned with patient's body and viewed from the participant's (first person) perspective. The self-bias effect was unaffected by the perspective/embodiment manipulation and it was strong across all conditions. However with two avatars performance on both self- and friend-match trials improved when the target stimulus appeared on the avatar adopting a first person perspective and aligned with the participant's body, when two avatars were shown in a social-communicative context. These selective improvements disappeared when two avatars turned their back on one another in a non-communicative setting. The data indicate that self- and friend-biases in perceptual matching are modulated by both how strongly stimuli align with the participant's perspective and body, and the social communicative situation. We suggest that self-biases can reflect an embodied representation of the self coded from a first-person perspectives. PMID- 27183401 TI - Trends and Developments Shaping the Future of Diagnostic Medical Imaging: 2015 Annual Oration in Diagnostic Radiology. PMID- 27183400 TI - Science to Practice: What Causes Arterial Infarction in Transforaminal Epidural Steroid Injections, and Which Steroid Is Safest? AB - Transforaminal epidural steroid injections (TFESIs) are associated with rare but devastating neurologic complications. Every published case has been associated with a particulate steroid suspension, and the presumed but not proven mechanism is embolization and occlusion of end arterioles. Through an in vivo murine model and in vitro experiments on human red blood cells (RBCs), the study by Laemmel et al (1) in this issue of Radiology elucidates the potential mechanisms for steroid induced vascular compromise. Unlike dexamethasone (a nonparticulate steroid solution), saline, and the particulate steroid cortivazol, other particulate steroids (prednisolone, methylprednisolone, and triamcinolone) caused often immediate and complete cessation of capillary blood flow, with RBC (not steroid particle) aggregates and alteration of RBC morphologic structure into spiculated RBCs. Thus, the study strengthens evidence in support of the higher safety profile in TFESI for dexamethasone, the nonparticulate and U.S. Food and Drug Administration-recommended steroid of choice, compared with particulate steroids. The results should not be considered proof that cortivazol has not or could not cause neurologic infarction during a TFESI. Rather, experiments such as those by Laemmel et al should foster more research, particularly in the arena of novel therapeutic agents (nonparticulate steroids and nonsteroidal drugs alike). PMID- 27183402 TI - Who Is Accountable for the Milestones? PMID- 27183403 TI - The Milestones Really Do Add Value. PMID- 27183404 TI - Imaging of Sports-related Hand and Wrist Injuries: Sports Imaging Series. AB - Hand and wrist injuries are common occurrences in amateur and professional sports and many of them are sport-specific. These can be divided into two categories: traumatic injuries and overuse injuries. The aim of this article is to review the most common hand and wrist sports-related lesions. Acute wrist injuries are predominantly bone fractures, such as those of the scaphoid, hamate hook, and ulnar styloid. Ligament lesions are more challenging for radiologists and may lead to carpal instability if undiagnosed. Overuse wrist injuries are mainly represented by tendinous disorders, with De Quervain syndrome and extensor carpi ulnaris tendon disorders being the most common among them; however, there are other possible disorders such as impaction syndromes, stress fractures, and neurovascular lesions. Finally, finger lesions, including closed-tendon injuries (mallet and boutonniere injuries, jersey finger, and boxer's knuckle), flexor pulley injuries, and skier's thumb, should also be detected. ((c)) RSNA, 2016 Online supplemental material is available for this article. PMID- 27183408 TI - Potential Utility of a Combined Approach with US and MR Arthrography to Image Medial Elbow Pain in Baseball Players. AB - Purpose To evaluate a combined imaging approach with both ultrasonography (US; conventional US and valgus stress US) and magnetic resonance (MR) arthrography in baseball players with medial elbow pain. Materials and Methods Institutional review board approval was obtained and the requirement for informed consent was waived. The study is compliant with HIPAA. Baseball players with medial elbow pain underwent US in addition to MR arthrography. Findings were assessed with each modality alone and both combined in this retrospective investigation. For the evaluation of ulnar collateral ligament (UCL) tears with stress US, the interval gapping of the medial elbow joint was measured between rest and valgus stress both at the injured and at the uninjured (contralateral) elbow. Surgical or arthroscopic correlation was available as the so-called gold standard. McNemar tests compared the accuracies of the imaging modalities. Results In this study, 144 baseball players had 191 findings of medial elbow pain, including 53 UCL tears. With stress US, joint gapping at the injured elbow greater than 1.0 mm compared with the contralateral elbow yielded a sensitivity, specificity, and accuracy of 96%, 81%, and 87%, respectively, for diagnosing UCL tears. With MR arthrography, the sensitivity, specificity, and accuracy for UCL tears were 81%, 91%, and 88%, respectively, and increased to 96% (P = .013, McNemar test), 99% (P = .023), and 98% (P < .001), respectively, when combined with US to a dual modality MR and US approach. For 31 patients with ulnar neuritis, the sensitivity, specificity, and accuracy increased from 74%, 92%, and 88%, respectively, with MR arthrography alone to 90% (P = .07, McNemar test), 100% (P < .001), and 98% (P < .001) combined with US. For the 59 myotendinous and the 48 osteochondral diagnoses, the sensitivity, specificity, and accuracy with MR arthrography alone were 93%, 93%, and 93%, and 94%, 98%, and 97%, respectively, with no additional diagnostic value from US. Conclusion The combined approach with both MR arthrography and US shows higher accuracy than each modality alone for the assessment of medial elbow pain. ((c)) RSNA, 2016. PMID- 27183409 TI - Case 234. PMID- 27183410 TI - Case 230: Congenital Inguinal Herniation of the Left Ureter (Extraperitoneal Form). AB - History A 52-year-old man with a history of urinary tract infections and a previous clinical diagnosis of left inguinal hernia presented to the nephrologist with recent onset of dysuria and increasing swelling in the left inguinoscrotal region in the absence of fever or scrotal trauma. There was no relevant surgical or family history. The general physical examination findings were unremarkable, with a normal abdomen at both visual inspection and palpation; urogenital examination revealed a small left-sided palpable mass of the testis, compatible with an inguinal hernia or hydrocele. At first, gray-scale and color Doppler ultrasonographic (US) images of the testes and the inguinoscrotal region were obtained. Contrast material-enhanced computed tomographic (CT) images of the lower abdomen and pelvis were then obtained to further evaluate the urinary tract. PMID- 27183411 TI - Predictors of Surgical Outcome in Cervical Spondylotic Myelopathy: MR Features Based on Axial Images Should Be Used in Combination with Other Parameters. PMID- 27183405 TI - MR Imaging Applications in Mild Traumatic Brain Injury: An Imaging Update. AB - Mild traumatic brain injury (mTBI), also commonly referred to as concussion, affects millions of Americans annually. Although computed tomography is the first line imaging technique for all traumatic brain injury, it is incapable of providing long-term prognostic information in mTBI. In the past decade, the amount of research related to magnetic resonance (MR) imaging of mTBI has grown exponentially, partly due to development of novel analytical methods, which are applied to a variety of MR techniques. Here, evidence of subtle brain changes in mTBI as revealed by these techniques, which are not demonstrable by conventional imaging, will be reviewed. These changes can be considered in three main categories of brain structure, function, and metabolism. Macrostructural and microstructural changes have been revealed with three-dimensional MR imaging, susceptibility-weighted imaging, diffusion-weighted imaging, and higher order diffusion imaging. Functional abnormalities have been described with both task mediated and resting-state blood oxygen level-dependent functional MR imaging. Metabolic changes suggesting neuronal injury have been demonstrated with MR spectroscopy. These findings improve understanding of the true impact of mTBI and its pathogenesis. Further investigation may eventually lead to improved diagnosis, prognosis, and management of this common and costly condition. ((c)) RSNA, 2016. PMID- 27183412 TI - Noninvasive Evaluation of Liver Fibrosis: Supersonic Shear Imaging or Acoustic Radiation Force Impulse Imaging? PMID- 27183413 TI - Reduction in Respiratory Motion Artifacts on Gadoxetate Acid-enhanced MR Images after Training Technicians. PMID- 27183414 TI - Some Clarifying Points Regarding Controversies in Contrast Material-induced Acute Kidney Injury. PMID- 27183416 TI - Ferenc A. Jolesz, MD. PMID- 27183415 TI - Hebert Leroy Abrams, MD. PMID- 27183418 TI - Dark High Density Dipolar Liquid of Excitons. AB - The possible phases and the nanoscale particle correlations of two-dimensional interacting dipolar particles is a long-sought problem in many-body physics. Here we observe a spontaneous condensation of trapped two-dimensional dipolar excitons with internal spin degrees of freedom from an interacting gas into a high density, closely packed liquid state made mostly of dark dipoles. Another phase transition, into a bright, highly repulsive plasma, is observed at even higher excitation powers. The dark liquid state is formed below a critical temperature Tc ~ 4.8 K, and it is manifested by a clear spontaneous spatial condensation to a smaller and denser cloud, suggesting an attractive part to the interaction which goes beyond the purely repulsive dipole-dipole forces. Contributions from quantum mechanical fluctuations are expected to be significant in this strongly correlated, long living dark liquid. This is a new example of a two-dimensional atomic-like interacting dipolar liquid, but where the coupling of light to its internal spin degrees of freedom plays a crucial role in the dynamical formation and the nature of resulting condensed dark ground state. PMID- 27183419 TI - [A methodological reminder for 2016]. PMID- 27183420 TI - [Burnout and risk of burnout in the teams of bone marrow transplant:
a multicentre Italian survey]. AB - . Burnout and risk of burnout in the Italian teams of bone marrow transplant: a multicentre survey. INTRODUCTION: The term burnout is used to describe a state of work-related psychological distress in healthcare employees characterized by three related, but independent, components: emotional exhaustion (EE), depersonalization (DP) and reduced personal accomplishment (PA). AIM: The aim of this study was to evaluate the prevalence of burnout and stress symptoms in physicians, nurses, and other healthcare professionals in Italian Bone Marrow Transplantation Units. METHODS: All personnel of a multidisciplinary group of the Italian Group of Bone Marrow Transplantation were asked to answer two different validated questionnaires: the Maslach Burnout Inventory (MBI) and the General Health Questionnaire (GHQ-12) for the assessment of general wellbeing. Logistic regression was used to investigate possible risk factors for burnout. RESULTS: This study showed a relatively low burnout prevalence (3.7%), however about 43.5% of health workers were at risk for developing a burnout syndrome. No personal or center characteristics seemed related to burnout risk, but there was a strong correlation between higher scores from the general health questionnaire and burnout risk. CONCLUSIONS: Results from our survey suggest that burnout is a relevant problem in transplant teams and as such strategies should be implemented to prevent it. PMID- 27183421 TI - [Contact with death or illness and career choice in non-medical health
professions and business students: a cross-sectional analysis]. AB - . Contact with death or illness and career choice in non-medical health professions and business students: a cross-sectional analysis. PURPOSE: It is anecdotally reported that a personal severe illness or the death of a significant person might be key reasons for the choice of a career in the non-medical health professions. AIM: The aim of the questionnaire was to explore past relevant life events before starting professional studies (severe personal illness; severe illness or death of a significant person; drug addiction of a relative or friend) by comparing students of nursing or other non medical health professions with business students. METHODS: An anonymous questionnaire with standardized closed questions was distributed in 2010 to a group of bachelor students of non-medical health professions (nursing, physiotherapy, occupational therapy and rescue care) and to a control group of business students at the University of Applied Sciences and Arts of Southern Switzerland. RESULTS: Students of non-medical health professions had been, compared to business students, significantly more exposed to severe illnesses or the death of a relative (OR 3.070, CI95% 1.716-5.494), to personal severe illness (OR 3.950, CI95% 1.384-11.279) and to addiction of a relative or friend (OR 2.672, CI95% 1.316-5.422) before starting their professional studies. CONCLUSIONS: This cross-sectional analysis suggests that exposure to a severe illness or death may play an important role in the choice of career, probably by supporting intrinsic motivations. Further research should explore the role of those past life experience in professional behavior. PMID- 27183422 TI - [Introduction]. PMID- 27183423 TI - [Italian validation of the Chemotherapy Induced Taste Alteration Scale]. AB - . Italian validation of the Chemotherapy Induced Taste Alteration Scale. Introdution. Taste alterations (TAs) are an underestimated side effect despite affecting 75% of chemo-radiotherapy patients. TAs may cause discomfort and food aversions up to loss of appetite and anorexia. The available instruments do not discriminate the different types of TAs. AIM: The aim of the study is to validate the Italian version of CiTAS, a 18-items scale that assesses specific TAs, symptoms of discomfort and their impact on patient nutrition. METHODS: A convenience sample of 243 patients with chemotherapy-induced taste alterations were enrolled. Data were analyzed for item consistency using Cronbach alpha and construct validity using factor analysis. RESULTS: The factor analysis identified four dimensions that explained a total variance of 67%: decline in basic taste, discomfort, phantogeusia and parageusia, and general taste alterations. The scale showed good validity (Cronbach's alpha = 0.82). CONCLUSIONS: The CiTAS enabled the valid and reliable measurement of specific symptoms of chemotherapy-induced TAs. It can be used both as a clinical tool and in future studies to evaluate the effectiveness of specific TAs treatments. PMID- 27183424 TI - [Validation of the Italian Clinical Learning Environment Instrument (SVIAT):
study protocol]. AB - . Validation of the Italian Clinical Learning Environment Instrument (SVIAT): study protocol. INTRODUCTION: Nursing students obtain most of their university credits in internship environments whose quality can affect their clinical learning. Several tools are available to measure the quality of the clinical learning environment (CLE) as perceived by students: these instruments developed in other countries, were validated in Italian but do not discriminate those CLEs capable (or not) to promote significant clinical learning. AIM: To validate an instrument to measure the capability of the CLE to generate clinical learning; the secondary aim is to describe the learning environments as perceived by nursing students according to individual course site and tutorial models adopted. METHODS: The study will be developed in three phases: a) instrument development and pilot phase, b) validation of the psychometric properties of the instrument and c) description of the CLEs as perceived by the students including factors/item confirmed in the validation process. Expected outcomes. A large validation, with more than 8,000 participating students is expected; the construct under lying will be confirmed through exploratory and confirmatory factor analysis and will report high internal consistency; the instrument will report also a high test-retest and inter-rater reliability; in addition, the instrument will demonstrate predictive ability by discriminating those units able (or not) to activate effective learning processes. PMID- 27183425 TI - [WHO analgesic pain ladder and weak opioids]. PMID- 27183426 TI - [Nursing Homes as a research priority area]. PMID- 27183427 TI - [From migrants to the duty of breaking the silence]. PMID- 27183428 TI - [On the road of migrants]. PMID- 27183430 TI - Micromechanical modelling of oil palm empty fruit bunch fibres containing silica bodies. AB - Experimental and numerical investigation was conducted to study the micromechanics of oil palm empty fruit bunch fibres containing silica bodies. The finite viscoelastic-plastic material model called Parallel Rheological Network model was proposed, that fitted well with cyclic and stress relaxation tensile tests of the fibres. Representative volume element and microstructure models were developed using finite element method, where the models information was obtained from microscopy and X-ray micro-tomography analyses. Simulation results showed that difference of the fibres model with silica bodies and those without ones is larger under shear than compression and tension. However, in comparison to geometrical effect (i.e. silica bodies), it is suggested that ultrastructure components of the fibres (modelled using finite viscoelastic-plastic model) is responsible for the complex mechanical behaviour of oil palm fibres. This can be due to cellulose, hemicellulose and lignin components and the interface behaviour, as reported on other lignocellulosic materials. PMID- 27183429 TI - Supplementation of host response by targeting nitric oxide to the macrophage cytosol is efficacious in the hamster model of visceral leishmaniasis and adds to efficacy of amphotericin B. AB - We investigated efficacy of nitric oxide (NO) against Leishmania donovani. NO is a mediator of host response to infection, with direct parasiticidal activity in addition to its role in signalling to evoke innate macrophage responses. However, it is short-lived and volatile, and is therefore difficult to introduce into infected cells and maintain inracellular concentrations for meaningful periods of time. We incorporated diethylenetriamine NO adduct (DETA/NO), a prodrug, into poly(lactide-co-glycolide) particles of ~200 nm, with or without amphotericin B (AMB). These particles sustained NO levels in mouse macrophage culture supernatants, generating an area under curve (AUC0.08-24h) of 591.2 +/- 95.1 mM * h. Free DETA/NO resulted in NO peaking at 3 h and declining rapidly to yield an AUC of 462.5 +/- 193.4. Particles containing AMB and DETA/NO were able to kill ~98% of promastigotes and ~76% of amastigotes in 12 h when tested in vitro. Promastigotes and amastigotes were killed less efficiently by particles containing a single drug- either DETA/NO (~42%, 35%) or AMB (~90%, 50%) alone, or by equivalent concentrations of drugs in solution. In a pre-clinical efficacy study of power >0.95 in the hamster model, DETA/NO particles were non-inferior to Fungizone(r) but not Ambisome(r), resulting in significant (~73%) reduction in spleen parasites in 7 days. Particles containing both DETA/NO and AMB were superior (~93% reduction) to Ambisome(r). We conclude that NO delivered to the cytosol of macrophages infected with Leishmania possesses intrinsic activity and adds significantly to the efficacy of AMB. PMID- 27183431 TI - Impact wear behavior of human tooth enamel under simulated chewing conditions. AB - Previous studies mostly focused on the sliding wear behavior of human teeth, and little effort has been made so far to study the impact wear of human teeth. The objective of this study was to investigate the impact wear process and mechanism of human tooth enamel and the influence of water content within enamel. In this paper, the impact wear behaviors of fresh and dried human tooth enamel against SiC ceramic have been investigated using a specially designed impact test machine. Tests lasting up to 5*10(3), 5*10(4), 2.5*10(5), 5.5*10(5), 8*10(5) and 1*10(6) cycles were conducted, respectively. Results showed that for the fresh enamel, the surface damage was dominated by plastic deformation at the early stage of impact wear. Iridescent rings appeared around the impact mark as a result of the accumulation and spread of plastic deformation. As the impact wear progressed, delamination occurred on the surface of enamel, and thus the iridescent rings gradually disappeared. Wear loss increased rapidly with the increase of impact cycles. When a wear particle layer was formed on the enamel surface, the wear rate decreased. It was found that the surface hardness of enamel increased with the impact cycles, and no cracks appeared on the cross section of wear scar. Compared with the fresh enamel, the fracture toughness of dried enamel decreased, and thus there were microcracks appearing on the cross section of wear scar. More obvious delamination occurred on the worn surface of dried enamel, and no iridescent rings were observed. The wear loss of dried enamel was higher than that of fresh enamel. In summary, the impact wear behavior of sound human tooth enamel was metal-like to some degree, and no subsurface cracking occurred. The water content within enamel could increase its fracture toughness and protect the surface from impact wear. The wear mechanism of human tooth enamel is determined by its microstructure. PMID- 27183432 TI - Characterization of compression behaviors of fully covered biodegradable polydioxanone biliary stent for human body: A numerical approach by finite element model. AB - This paper presents a study of the compression behaviors of fully covered biodegradable polydioxanone biliary stents (FCBPBs) developed for human body by finite element method. To investigate the relationship between the compression force and structure parameter (monofilament diameter and braid-pin number), nine numerical models based on actual biliary stent were established, the simulation and experimental results are in good agreement with each other when calculating the compression force derived from both experiment and simulation results, indicating that the simulation results can be provided a useful reference to the investigation of biliary stents. The stress distribution on FCBPBSs was studied to optimize the structure of FCBPBSs. In addition, the plastic dissipation analysis and plastic strain of FCBPBSs were obtained via the compression simulation, revealing the structure parameter effect on the tolerance. PMID- 27183433 TI - Monitoring Nitric Oxide in Subcellular Compartments by Hybrid Probe Based on Rhodamine Spirolactam and SNAP-tag. AB - By connection of O(6)-benzylguanine (BG) to an "o-phenylenediamine-locked" rhodamine spirolactam responsive to nitric oxide (NO), a novel substrate (TMR-NO BG) of genetically encoded SNAP-tag has been constructed. In living cells, labeling SNAP-tag fused proteins with TMR-NO-BG will in situ generate corresponding probe-protein conjugates (TMR-NO-SNAP) that not only inherit high NO sensitivity from the small-molecule parent but also guarantee the site specificity to the designated subcellular compartments such as the mitochondrial inner membrane, nucleus, and cytoplasm. In two representative cellular processes, TMR-NO-BG demonstrates its applicability to monitor endogenous subcellular NO in the activated RAW264.7 cells stimulated by lipopolysaccharide and in the apoptotic COS-7 cells induced by etoposide. PMID- 27183434 TI - The Effect of G2 Adjuvant on Gene Expression and Delivery of NKG2D Receptor on NK Cells in Peripheral Blood. AB - INTRODUCTION: Natural killer (NK) cells are a subset of lymphocytes in humans that release cytokines such as tumor necrosis factor alpha and interferon gamma gamma during infection. NKG2D is one of the most important stimulating NK receptors binding MIC-A, MIC-B, and ULBPs, which leads to activation of NK cells against tumor cells. In this study, the authors evaluated the effect of G2 adjuvant on gene expression and delivery of NKG2D receptor on NK cells in peripheral blood. MATERIALS AND METHODS: Peripheral blood mononuclear cells were isolated from venous blood obtained from healthy volunteers after adding G2 adjuvant within 12, 24, and 48 hours of incubation. Then, total RNA was extracted from the cells, cDNA synthesis was performed, and gene expression was evaluated by real-time PCR. In addition, NK cells were stained with the appropriate monoclonal antibodies, and the receptors expressed on cell surface were quantified. RESULTS: G2 adjuvant leads to upregulation of gene expression and increases the expression of NKG2D receptor on the surface of NK cells after incubation. CONCLUSION: The findings of this study demonstrated that G2 adjuvant can increase NK cell cytotoxicity. It may play an important role in killing tumor cells, preventing tumor growth and metastasis. PMID- 27183435 TI - Decreased LRIG1 in Human Ovarian Cancer Cell SKOV3 Upregulates MRP-1 and Contributes to the Chemoresistance of VP16. AB - The leucine-rich repeats and immunoglobulin-like domains (LRIG) are used as tumor suppressors in clinical applications. Although the LRIG has been identified to manipulate the cell proliferation via various oncogenic receptor tyrosine kinases in diverse cancers, its role in multidrug resistance needs to be further elucidated, especially in human ovarian cancer. We herein established that the etoposide (VP16)-resistant SKOV3 human ovarian cancer cell clones (SKOV3/VP16 cells) and mRNA expression of LRIG1 were significantly reduced by the treatment of VP16 in a concentration-dependent manner. Moreover, downregulated LRIG1 in SKOV3 could enhance the colony formation and resist the inhibition of proliferation by VP16, leading to the elevated expression of Bcl-2 and decreased apoptosis of SKOV3. Interestingly, our results uncovered that the multidrug resistance-associated protein 1 (MRP-1) was upregulated for the chemoresistance of VP16. To overcome the chemoresistance of SKOV3, SKOV3/VP16 was ectopically expressed of LRIG1. We found that the inhibition of VP16 on colony formation and proliferation was remarkably enhanced with increased apoptosis in SKOV3/VP16. Furthermore, the expression of MRP-1 and Bcl-2 was also inhibited, suggesting that the LRIG1could negatively control MRP-1 and the apoptosis to improve the sensitivity of VP16-related chemotherapy. PMID- 27183436 TI - Inhibition of Human Glioma Cell Proliferation Caused by Knockdown of Utrophin Using a Lentivirus-Mediated System. AB - BACKGROUND: Glioma is the most devastating brain tumor worldwide. Previous studies showed that UTRN (utrophin) was related to cancers, but its role in glioma cells remains uncovered. MATERIALS AND METHODS: RNAi was used to knockdown UTRN in U251 cells using lentivirus system. The knockdown efficiency was validated by real-time quantitative PCR. Cell proliferation, cell cycle, and apoptosis progression were determined by MTT, colony formation analysis, and flow cytometry analysis. Furthermore, some apoptotic markers were examined by Western blot assay. RESULTS: Most cells were infected. Cell proliferation and colony formation ability were suppressed in U251 cells lacking UTRN. Moreover, there was an obvious increase in cell percentage in the G2/M phases and a significant apoptosis in U251 cells after UTRN silencing. Further investigation demonstrated that UTRN knockdown activated caspase and PARP pathways. CONCLUSIONS: Knockdown of UTRN expression by shRNA evidently inhibited cell proliferation and promoted cell apoptosis in glioma cells. PMID- 27183437 TI - A Freeze-Dried Kit for the Preparation of (188)Re-HEDP for Bone Pain Palliation: Preparation and Preliminary Clinical Evaluation. AB - (188)Re-HEDP is an established radiopharmaceutical used for pain palliation in patients with osseous metastasis. Considering commercial availability of (188)W/(188)Re generator, the accessibility to a lyophilized kit would make preparation of this radiopharmaceutical feasible at the hospital radiopharmacy having access to a generator. A protocol for the preparation of a single-vial lyophilized hydroxyethane 1,1-diphosphonic acid (HEDP) kit was developed and its consistency was checked by preparing six batches. Each sterile lyophilized kit prepared as per the protocol contained 9 mg of HEDP, 3 mg of gentisic acid, and 4 mg of SnCl2.2H2O. Randomly selected kits from all six batches were subjected to thorough quality control tests that were passed by all batches. (188)Re-HEDP could be prepared by addition of 1 mL of freshly eluted Na(188)ReO4 (up to 3700 MBq) containing 1 MUmol of carrier ReO4(-) (perrhenate) and heating at 100 degrees C for 15 minutes. (188)Re-HEDP with >95% radiochemical purity could be consistently prepared using the lyophilized kits. Sterile (188)Re-HEDP prepared using the lyophilized kit was evaluated in patients with osseous metastasis. Post therapy images of the patient were compared with (99m)Tc-MDP bone scan and found to be satisfactory. The bone-to-background as well as tumor-to-normal bone uptake ratio was found to be significant. All patients who received therapy reported significant pain relief within a week to 10 days post-administration of (188)Re HEDP. PMID- 27183438 TI - Overexpression of Annexin II Receptor-Induced Autophagy Protects Against Apoptosis in Uveal Melanoma Cells. AB - Uveal melanoma is the most common primary malignant intraocular tumor in adults and still lacks effective systemic therapies. Annexin A2 receptor (AXIIR), a receptor for Annexin II, was demonstrated to play an important role in multiple cells, but its role in uveal melanoma cells remains exclusive. Herein, the authors reported that overexpression of AXIIR was able to reduce cell viability and activate apoptosis apparently in the Mum2C uveal melanoma cell line. Meanwhile, overexpression of AXIIR could induce autophagy and increase autophagy flux. After autophagy was inhibited by chloroquine, enhanced apoptosis and cytotoxicity could be detected. In summary, these data highlighted the crucial role of AXIIR in reducing Mum2C cell viability through inducing apoptosis, while autophagy played a protective role in this process. Interference of this gene may be a promising method for uveal melanoma therapy and combination with specific inhibitor of autophagy may serve as a supplementary. PMID- 27183439 TI - Clonal genotype and population structure inference from single-cell tumor sequencing. AB - Single-cell DNA sequencing has great potential to reveal the clonal genotypes and population structure of human cancers. However, single-cell data suffer from missing values and biased allelic counts as well as false genotype measurements owing to the sequencing of multiple cells. We describe the Single Cell Genotyper (https://bitbucket.org/aroth85/scg), an open-source software based on a statistical model coupled with a mean-field variational inference method, which can be used to address these problems and robustly infer clonal genotypes. PMID- 27183440 TI - Automated mapping of phenotype space with single-cell data. AB - Accurate identification of cell subsets in complex populations is key to discovering novelty in multidimensional single-cell experiments. We present X shift (http://web.stanford.edu/~samusik/vortex/), an algorithm that processes data sets using fast k-nearest-neighbor estimation of cell event density and arranges populations by marker-based classification. X-shift enables automated cell-subset clustering and access to biological insights that 'prior knowledge' might prevent the researcher from discovering. PMID- 27183441 TI - Flyception: imaging brain activity in freely walking fruit flies. AB - Genetically encoded calcium sensors have enabled monitoring of neural activity in vivo using optical imaging techniques. Linking neural activity to complex behavior remains challenging, however, as most imaging systems require tethering the animal, which can impact the animal's behavioral repertoire. Here, we report a method for monitoring the brain activity of untethered, freely walking Drosophila melanogaster during sensorially and socially evoked behaviors to facilitate the study of neural mechanisms that underlie naturalistic behaviors. PMID- 27183442 TI - Local Burn Injury Promotes Defects in the Epidermal Lipid and Antimicrobial Peptide Barriers in Human Autograft Skin and Burn Margin: Implications for Burn Wound Healing and Graft Survival. AB - Burn injury increases the risk of morbidity and mortality by promoting severe hemodynamic shock and risk for local or systemic infection. Graft failure due to poor wound healing or infection remains a significant problem for burn subjects. The mechanisms by which local burn injury compromises the epithelial antimicrobial barrier function in the burn margin, containing the elements necessary for healing of the burn site, and in distal unburned skin, which serves as potential donor tissue, are largely unknown. The objective of this study was to establish defects in epidermal barrier function in human donor skin and burn margin, to identify potential mechanisms that may lead to graft failure and/or impaired burn wound healing. In this study, we established that epidermal lipids and respective lipid synthesis enzymes were significantly reduced in both donor skin and burn margin. We further identified diverse changes in the gene expression and protein production of several candidate skin antimicrobial peptides (AMPs) in both donor skin and burn margin. These results also parallel changes in cutaneous AMP activity against common burn wound pathogens, aberrant production of epidermal proteases known to regulate barrier permeability and AMP activity, and greater production of proinflammatory cytokines known to be induced by AMPs. These findings suggest that impaired epidermal lipid and AMP regulation could contribute to graft failure and infectious complications in subjects with burn or other traumatic injury. PMID- 27183444 TI - Pain and infection: pathogen detection by nociceptors. PMID- 27183445 TI - Moving beyond the eigenvalue greater than one retention criteria in pain phenotyping research. PMID- 27183443 TI - Burns: Pathophysiology of Systemic Complications and Current Management. AB - As a result of many years of research, the intricate cellular mechanisms of burn injury are slowly becoming clear. Yet, knowledge of these cellular mechanisms and a multitude of resulting studies have often failed to translate into improved clinical treatment for burn injuries. Perhaps the most valuable information to date is the years of clinical experience and observations in the management and treatment of patients, which has contributed to a gradual improvement in reported outcomes of mortality. This review provides a discussion of the cellular mechanisms and pathways involved in burn injury, resultant systemic effects on organ systems, current management and treatment, and potential therapies that we may see implemented in the future. PMID- 27183446 TI - The "paradox" of neuropathic pain associated with small-fiber lesions in the context of fibromyalgia. PMID- 27183447 TI - Reply. PMID- 27183448 TI - What is the meaning of "small-fiber polyneuropathy" in fibromyalgia? An alternate answer. PMID- 27183449 TI - Reply. PMID- 27183450 TI - Erratum. PMID- 27183451 TI - Vascular calcification and intradialytic hypotension in hemodialysis patients: Clinical relevance and impact on morbidity and mortality. AB - BACKGROUND: Vascular calcification (VC) and intradialytic hypotension (IDH) indicate morphological and functional disorders of the cardiovascular system in hemodialysis (HD) patients. However, their relationship and combined effects on clinical outcomes remain undetermined. METHODS: HD patients (n=443) whose plain chest radiographs were examined for aortic arch VC were included. IDH was defined as nadir systolic blood pressure <90mmHg or need for bolus fluid. We investigated the relationship between VC and IDH, and their clinical significance for cardiovascular events (CVEs) and death. RESULTS: VC was found in 57 HD patients (12.9%). IDH was more prevalent in patients with VC compared with those without VC (35.1% vs. 18.7%; P=0.004). VC was independently associated with a 2.12-fold increase in the risk of IDH (95% confidence interval [CI], 1.03-4.36). In multivariate analysis, compared with patients with neither VC nor IDH, the coexistence of VC and IDH was independently associated with death (hazard ratio [HR], 3.83; 95% CI, 1.62-9.08) and CVE (HR, 3.77; 95% CI, 1.53-9.33), whereas VC or IDH alone was not. Patients with both VC and IDH had the highest risk for a composite event (HR, 3.56; 95% CI, 1.79-7.08). Significant synergistic interaction was observed between VC and IDH (P for interaction=0.009). CONCLUSIONS: VC was independently associated with IDH. Coexistence of VC and IDH was associated with higher risk of death and CVEs than either factor alone. There was a synergistic interaction between VC and IDH for the risk of a composite event. PMID- 27183452 TI - Coronary flow reserve as a link between exercise capacity, cardiac systolic and diastolic function. AB - BACKGROUND: Decreased coronary flow reserve (CFR) is associated with increased risk of adverse cardiovascular events. We sought to investigate how CFR from left anterior descending (LAD) coronary artery reflects clinical markers of cardiac function. METHODS: We enrolled 400 patients referred for myocardium perfusion scintigraphy due to chest pain at Sahlgrenska University Hospital in Gothenburg, Sweden. Transthoracic echocardiography including adenosine-assisted CFR in LAD was performed at a separate occasion. RESULTS: Median age was 62years (range 32 83) and 47% were female. Prior myocardial infarction had occurred in 28% of the population. In adjusted multivariate models, CFR in LAD was associated with echocardiography left ventricle ejection fraction at rest (beta=0.97, p=0.033) as well as under stress (beta=1.52, p=0.0056) and maximum exercise capacity (beta=6.27, p=0.026). CFR in LAD outweighed left ventricle ejection fraction as the determinant of maximum exercise capacity. Hyperaemic diastolic mitral annulus peak velocity measured by vector velocity imaging was inversely associated with LAD CFR (beta=-0.39, p=0.0077). In subgroup analyses these findings were associated with normal coronary perfusion in myocardium perfusion scintigraphy. CONCLUSIONS: In patients with angina-like symptoms CFR measured in LAD reflects well both systolic and diastolic cardiac function emphasizing the essential role of myocardial microvascular circulation in cardiac physiology. PMID- 27183453 TI - Quantitative comparison of 2D and 3D late gadolinium enhancement MR imaging in patients with Fabry disease and hypertrophic cardiomyopathy. AB - BACKGROUND: This study aims to determine whether the quantification of myocardial fibrosis in patients with Fabry disease (FD) and hypertrophic cardiomyopathy (HCM) using a late gadolinium enhancement (LGE) singlebreath-hold three dimensional (3D) inversion recovery magnetic resonance (MR) imaging sequence is comparable with a clinically established two-dimensional (2D) multi-breath-hold sequence. METHODS: In this retrospective, IRB-approved study, 40 consecutive patients (18 male; mean age 50+/-17years) with Fabry disease (n=18) and HCM (n=22) underwent MR imaging at 1.5T. Spatial resolution was the same for 3D and 2D images (field-of-view, 350*350mm(2); in-plane-resolution, 1.2*1.2mm(2); section-thickness, 8mm). Datasets were analyzed for subjective image quality; myocardial and fibrotic mass, and total fibrotic tissue percentage were quantified. RESULTS: There was no significant difference in subjective image quality between 3D and 2D acquisitions (P=0.1 and P=0.3) for either disease. In patients with Fabry disease there were no significant differences between 3D and 2D acquisitions for myocardial mass (P=0.55), fibrous tissue mass (P=0.89), and total fibrous percentage (P=0.67), with good agreement between acquisitions according to Bland-Altman analyses. In patients with HCM there were also no significant differences between acquisitions for myocardial mass (P=0.48), fibrous tissue mass (P=0.56), and total fibrous percentage (P=0.67), with good agreement according to Bland-Altman analyses. Acquisition time was significantly shorter for 3D (25+/-5s) as compared to the 2D sequence (349+/-62s, P<0.001). CONCLUSIONS: In patients with Fabry disease and HCM, 3D LGE imaging provides equivalent diagnostic information in regard to quantification of myocardial fibrosis as compared with a standard 2D sequence, but at superior acquisition speed. PMID- 27183454 TI - Effect of training general practitioners in drug treatment of newly detected heart failure patients with reduced or preserved ejection fraction: A cluster randomized trial. AB - OBJECTIVE: To assess the effect of training general practitioners (GPs) in the optimization of drug treatment for newly detected heart failure (HF). DESIGN: Cluster randomized trial comparing the training programme to care as usual. PARTICIPANTS: Community-dwelling older persons with a new HF diagnosis after diagnostic work-up. METHODS: Thirty GPs were randomized to care as usual or the training. Sixteen GPs of the latter group received a half-day training on optimizing HF medication in HF patients with a reduced (HFrEF), or with a preserved ejection fraction (HFpEF). At baseline and after six months of follow up, the 46 HF patients in the intervention group and the 46 cases in the care as usual group were assessed on medication use, functionality, health status, and health care visits. RESULTS: After 6months, uptake of HF medication and health status were similar in the two groups. Interestingly, patients in the intervention group had a longer walking distance with the six-minute walk test than those in the care as usual group (mean difference in all-type HF 28.0 (95% CI 2.9 to 53.1) meters; HFpEF patients 28.2 (95% CI 8.8 to 47.5) meters and HFrEF patients 55.9 (95% CI -16.3 to 128.1) meters). They also had more HF-related GP visits (RR 1.8, 95% CI 1.3 to 2.5) and fewer visits to the cardiologist (RR 0.6, 95% CI 0.3 to 1.1). CONCLUSIONS: Training GPs in optimization of drug treatment of newly detected HFrEF and HFpEF did not clearly increase HF medication, but resulted in improvement in walking distance. PMID- 27183456 TI - How Patent Troll Legislation Can Increase Timely Access to Generic Drugs. PMID- 27183457 TI - How does the motion of the surrounding molecules depend on the shape of a folding molecular motor? AB - Azobenzene based molecules have the property of isomerizing when illuminated. In relation with that photoisomerization property, azobenzene containing materials are the subject of unexplained massive mass transport. In this work we use an idealised rectangular chromophore model to study the dependence of the isomerization induced transport on the chromophore's dimensions. Our results show the presence of a motor arm length threshold for induced transport, which corresponds to the host molecule's size. Above the threshold, the diffusive motions increase proportionally to the chromophore's length. Intriguingly, we find only a very small chromophore width dependence of the induced diffusive motions. Our very simplified motor reproduces relatively well the behavior observed using the real DR1 motor molecule, suggesting that the complex closing procedure and the detailed shape of the motor are not necessary to induce the molecular motions. PMID- 27183455 TI - A contemporary cross-sectional study on dyslipidemia management, cardiovascular risk status, and patients' quality of life in Greece: The CHALLENGE study. AB - BACKGROUND: Prior studies conducted in Greece consistently indicate that dyslipidemia is suboptimally managed, while the burden of cardiovascular disease (CVD) and related risk factors is rising. METHODS: CHALLENGE was a multicenter, cross-sectional study carried out following the publication of guidelines advocating stricter low-density lipoprotein cholesterol (LDL-C) targets. It primarily aimed to depict LDL-C target attainment, and to assess the cardiovascular risk status and quality of life (QoL) of patients treated in a primary or secondary CVD prevention setting who had received any medical intervention for cardiovascular risk modification within 6months of enrollment. RESULTS: Between December 2012 and April 2013, 500 patients (55% males) aged (mean+/-SD) 62.0+/-11.7years, participated in the study. Cardiovascular risk according to the 2011 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines was 'very high', 'high', and 'moderate' in 61.2%, 23.4%, and 15.4%, respectively. Overall, 92.0% of patients were on lipid-lowering treatment, yet only 23.3% had attained their ESC/EAS-defined LDL-C target. LDL-C target attainment was more likely among 'moderate' versus 'very high' cardiovascular risk patients (odds ratio: 4.04; 95% confidence interval: 2.32 7.06; p<0.001). QoL improved as cardiovascular risk decreased (EQ-VAS 71.8+/-16.2 in the 'very high' versus 78.3+/-15.1 and 80.3+/-15.7 in the 'high' and 'moderate' risk groups; p<0.001). Time constraints and difficulties in implementation in daily practice were the investigator's main barriers for guideline utilization. CONCLUSIONS: During contemporary management of dyslipidemia in Greece, LDL-C target attainment is suboptimal. There is an undoubted need for improvement and implementation of cardiovascular risk assessment in routine clinical practice. PMID- 27183458 TI - Spatio-temporal trends and monitoring design of perfluoroalkyl acids in the eggs of gull (Larid) species from across Canada and parts of the United States. AB - A large spatial dataset of perfluoroalkyl acid (PFAA) concentrations in eggs of herring gulls (Larus argentatus or congeneric species) collected from late April to early June between 2009 and 2014 from 28 colonies across Canada and parts of the Unites States was used to evaluate location-specific patterns in chemical concentrations and to generate hypotheses on the major sources affecting PFAA distributions. The highly bioaccumulative perfluorooctane sulfonic acid (PFOS) as well as other perfluoroalkyl sulfonic acids (PFSAs) showed the greatest concentrations in eggs from the lower Great Lakes of southern Ontario as well as from the St. Lawrence River. Despite the 2000 to 2002 phase-out of PFOS and related C8 chemistry by the major manufacturer at the time, ongoing losses from consumer products during use and disposal in urban/industrial locations continue to be major sources to the environment and are influencing the spatial trends of PFOS in Canada. In comparison to PFOS, perfluoroalkyl carboxylic acids (PFCAs) were not as concentrated in eggs in close proximity to urbanized/industrialized centers, but had surprisingly elevated levels in relatively remote regions such as Great Slave Lake, NT and East Bay in Hudson Bay, NU. The present results support the hypothesis that atmospheric transport and degradation of precursor chemicals, such as the fluorotelomer alcohols 8:2 FTOH and 10:2 FTOH, are influencing the spatial trends of PFCAs in Canada. A power analysis conducted on a representative urbanized/industrialized colony in the Toronto Harbour, ON, and a relatively remote colony in Lake Superior, emphasized the importance of consistent and long-term data collection in order to detect the anticipated changes in PFAA concentrations in Canadian gull eggs. PMID- 27183459 TI - Phytostabilization of mine tailings using compost-assisted direct planting: Translating greenhouse results to the field. AB - Standard practice in reclamation of mine tailings is the emplacement of a 15 to 90cm soil/gravel/rock cap which is then hydro-seeded. In this study we investigate compost-assisted direct planting phytostabilization technology as an alternative to standard cap and plant practices. In phytostabilization the goal is to establish a vegetative cap using native plants that stabilize metals in the root zone with little to no shoot accumulation. The study site is a barren 62 hectare tailings pile characterized by extremely acidic pH as well as lead, arsenic, and zinc each exceeding 2000mgkg(-1). The study objective is to evaluate whether successful greenhouse phytostabilization results are scalable to the field. In May 2010, a 0.27ha study area was established on the Iron King Mine and Humboldt Smelter Superfund (IKMHSS) site with six irrigated treatments; tailings amended with 10, 15, or 20% (w/w) compost seeded with a mix of native plants (buffalo grass, arizona fescue, quailbush, mountain mahogany, mesquite, and catclaw acacia) and controls including composted (15 and 20%) unseeded treatments and an uncomposted unseeded treatment. Canopy cover ranging from 21 to 61% developed after 41 months in the compost-amended planted treatments, a canopy cover similar to that found in the surrounding region. No plants grew on unamended tailings. Neutrophilic heterotrophic bacterial counts were 1.5 to 4 orders of magnitude higher after 41months in planted versus unamended control plots. Shoot tissue accumulation of various metal(loids) was at or below Domestic Animal Toxicity Limits, with some plant specific exceptions in treatments receiving less compost. Parameters including % canopy cover, neutrophilic heterotrophic bacteria counts, and shoot uptake of metal(loids) are promising criteria to use in evaluating reclamation success. In summary, compost amendment and seeding, guided by preliminary greenhouse studies, allowed plant establishment and sustained growth over 4years demonstrating feasibility for this phytostabilization technology. PMID- 27183460 TI - Chloride sources in urban and rural headwater catchments, central New York. AB - Road salt used as a deicing agent in winter months has become an emerging contaminant to streams and groundwater. In central New York, road salts are applied heavily during winter months. Recognizing potential sources of salinity to a river may reveal processes controlling the salinization of freshwater systems, with implications for future management practices. The Tioughnioga River, located in central New York, is a headwater of the Susquehanna River, which flows into the Chesapeake Bay. Salinity of the Tioughnioga River water has been increasing since the late 1930s. In this study, water samples were collected weekly at the East and West Branches of the Tioughnioga River from 2012 to 2014. We characterize natural and anthropogenic sources of salinity in the Tioughnioga River, using two independent approaches: (1) chloride to bromide ratios (Cl/Br) and (2) linear discriminant analysis. Ratios of Cl/Br suggest that road salt runoff influence is notable in both branches, but is more significant in the West Branch, consistent with a greater area of urban land. Linear discriminant analysis confirms the results of Cl/Br in the West Branch and further indicates presence of Appalachian Basin Brines in the East Branch, although their contribution may be volumetrically small. Longitudinal stream Cl concentration profiles indicate that sources of pollution are particularly concentrated around urban areas. Residence time of Cl in the watershed is estimated to be approximately 20 to 30years using a mixing model, suggesting that stream Cl concentrations likely will continue to rise for several decades. PMID- 27183461 TI - Biotic nitrosation of diclofenac in a soil aquifer system (Katari watershed, Bolivia). AB - Up till now, the diclofenac (DCF) transformation into its nitrogen-derivatives, N nitroso-DCF (NO-DCF) and 5-nitro-DCF (NO2-DCF), has been mainly investigated in wastewater treatment plant under nitrification or denitrification processes. This work reports, for the first time, an additional DCF microbial mediated nitrosation pathway of DCF in soil under strictly anoxic conditions probably involving codenitrification processes and fungal activities. This transformation pathway was investigated by using field observations data at a soil aquifer system (Katari watershed, Bolivia) and by carrying out soil slurry batch experiments. It was also observed for diphenylamine (DPA). Field measurements revealed the occurrence of NO-DCF, NO2-DCF and NO-DPA in groundwater samples at concentration levels in the 6-68s/L range. These concentration levels are more significant than those previously reported in wastewater treatment plant effluents taking into account dilution processes in soil. Interestingly, the p benzoquinone imine of 5-OH-DCF was also found to be rather stable in surface water. In laboratory batch experiments under strictly anoxic conditions, the transformation of DCF and DPA into their corresponding N-nitroso derivatives was well correlated to denitrification processes. It was also observed that NO-DCF evolved into NO2-DCF while NO-DPA was stable. In vitro experiments showed that the Fisher-Hepp rearrangement could not account for NO2-DCF formation. One possible mechanism might be that NO-DCF underwent spontaneous NO loss to give the resulting intermediates diphenylaminyl radical or nitrenium cation which might evolve into NO2-DCF in presence of NO2 radical or nitrite ion, respectively. PMID- 27183462 TI - Long-term changes in temperate stream invertebrate communities reveal a synchronous trophic amplification at the turn of the millennium. AB - The positive effects of water quality improvement on stream biodiversity in the temperate regions are expected to be at risk with the projected climatic changes. However, the processes and mechanisms behind the predicted threats remain uncertain. From long-term series of benthic invertebrate samples from temperate rivers and streams in France, we analyzed diversity and composition shifts over time in relation to geographic elements and human stressors. Mechanisms for community changes were investigated with a trait-based analysis for the entire dataset and for a selected caddisfly community module. We observed a 42% increase in the taxonomic richness of stream invertebrate communities over the last 25years. A gradual trend induced by water quality improvement was distinguished from a more abrupt climate change-induced shift in communities around the year 2000. Trophic amplification - the intensification of trophic interactions and pathways through the food web - was identified as the mechanism behind the strong community shift. Four lines of evidence for this trophic amplification are highlighted: (i) higher dissolved oxygen concentrations indicated a shift in primary production, (ii) the trait-based analysis of entire communities showed a bottom-up food web amplification, (iii) the trait-based analysis of the community module evidenced feeding strategy shifts and increased food web interactions, and (iv) the abundance analysis of the community module showed a productivity increase. These results lend credit to persistent investments in water quality for improving stream biodiversity, and contrary to expectation, climate change impacts seem so far to have reinforced these positive effects. PMID- 27183463 TI - On-Task in a Box: An evaluation of a package-ready intervention for increasing levels of on-task behavior and academic performance. AB - The present study tested the efficacy of the On-Task in a Box program for increasing on-task behavior and academic accuracy of highly off-task students. Six students in 2nd and 3rd grades were identified by their classroom teacher as highly off-task. Following identification, the students participated in the On Task in a Box intervention. Results of the study found immediate and large effects, which were maintained following discontinuation of the intervention. Collateral improvements in accuracy on math probes completed during independent seatwork were also observed. Teacher and participant responses to intervention acceptability questionnaires indicate the program was viewed positively. Implications for school-based adoption of the program are presented, and limitations and future research are discussed. (PsycINFO Database Record PMID- 27183464 TI - Exploratory human PET study of the effectiveness of (11)C-ketoprofen methyl ester, a potential biomarker of neuroinflammatory processes in Alzheimer's disease. AB - INTRODUCTION: Neuroinflammatory processes play an important role in the pathogenesis of Alzheimer's disease (AD). As a biomarker of neuroinflammatory processes, we designed (11)C-labeled ketoprofen methyl ester ([(11)C]KTP-Me) to increase the blood-brain barrier permeability of ketoprofen (KTP), a selective cyclooxygenase-1 (COX-1) inhibitor. Animal studies indicated that [(11)C]KTP-Me enters the brain and accumulates in activated microglia of inflammatory lesions. In a first-in-human study, we reported that [(11)C]KTP-Me is a safe positron emission tomography (PET) tracer and enters the brain; the radioactivity is washed out from normal cerebral tissue. Here we explored the efficacy of [(11)C]KTP-Me as a diagnostic biomarker of neuroinflammatory processes in AD. METHODS: [(11)C]KTP-Me was synthesized by rapid C-[(11)C]methylation of [(11)C]CH3I and the corresponding arylacetate precursor. Nine subjects (four healthy subjects, two Pittsburgh compound-B (PiB)-positive patients with mild cognitive impairment (MCI), and three PiB-positive AD patients) underwent a dynamic brain PET scan for 70min after injection. We evaluated differences in cortical retention and washout rate in the brain between healthy subjects and MCI/AD patients. RESULTS: A brain distribution pattern reflecting blood flow in the early-phase image was seen in both healthy subjects and MCI/AD patients. Cortical activity gradually cleared in all groups. However, we observed no obvious difference in the washout rate between healthy subjects and MCI/AD patients or between MCI and AD patients. CONCLUSIONS: [(11)C]KTP-Me cannot be useful as a potential diagnostic biomarker for MCI/AD. Further improvements in binding affinity and specificity, etc., are needed to be a diagnostic biomarker of neuroinflammation in AD. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: [(11)C]KTP-Me is a new tracer that targets COX-1. [(11)C]KTP-Me is expected to be a diagnostic biomarker of neuroinflammation in AD in the future. The effectiveness was limited in a small number of AD patients. Therefore, further studies are needed to clarify the usefulness of [(11)C]KTP-Me. PMID- 27183466 TI - Investigation of the accuracy of MV radiation isocentre calculations in the Elekta cone-beam CT software XVI. AB - Accurate determination of the megavoltage (MV) radiation isocentre of a linear accelerator (linac) is an important task in radiotherapy. The localization of the MV radiation isocentre is crucial for correct calibration of the in-room lasers and the cone-beam CT scanner used for patient positioning prior to treatment. Linac manufacturers offer tools for MV radiation isocentre localization. As a user, there is no access to the documentation for the underlying method and calculation algorithm used in the commercial software. The idea of this work was to evaluate the accuracy of the software tool for MV radiation isocentre calculation as delivered by Elekta using independent software. The image acquisition was based on the scheme designed by the manufacturer. Eight MV images were acquired in each series of a ball-bearing (BB) phantom attached to the treatment couch. The images were recorded at cardinal angles of the gantry using the electronic portal imaging device (EPID). Eight Elekta linacs with three different types of multileaf collimators (MLCs) were included in the test. The influence of MLC orientation, x-ray energy, and phantom modifications were examined. The acquired images were analysed using the Elekta x-ray volume imaging (XVI) software and in-house developed (IHD) MATLAB code. Results from the two different software were compared. A discrepancy in the longitudinal direction of the isocentre localization was found averaging 0.23 mm up to a maximum of 0.75 mm. The MLC orientation or the phantom asymmetry in the longitudinal direction do not appear to cause the discrepancy. The main cause of the differences could not be clearly identified. However, it is our opinion that the commercial software delivered by the linac manufacturer should be improved to reach better stability and precise results in the MV radiation isocentre calculations. PMID- 27183465 TI - Efficient radiosynthesis and non-clinical safety tests of the TSPO radioprobe [(18)F]FEDAC: Prerequisites for clinical application. AB - INTRODUCTION: [(18)F]FEDAC ([(18)F]1) has potent binding affinity and selectivity for translocator protein (18kDa, TSPO), and has been used to noninvasively visualize neuroinflammation, lung inflammation, acute liver damage, nonalcoholic fatty liver disease, and liver fibrosis. We had previously synthesized [(18)F]1 in two steps: (i) preparation of [(18)F]fluoroethyl bromide and (ii) coupling of [(18)F]fluoroethyl bromide with the appropriate precursor (2) for labeling. In this study, to clinically utilize [(18)F]1 as a PET radiopharmaceutical and to transfer the production technique of [(18)F]1 to other PET centers, we simplified its preparation by using a direct, one-step, tosyloxy-for-fluorine substitution. We also performed an acute toxicity study as a major non-clinical safety test, and determined radiometabolites using human liver microsomes. METHODS: [(18)F]1 was prepared via direct (18)F-fluorination by heating the corresponding tosylated derivative (3) with [(18)F]fluoride as its Kryptofix 222 complex in dimethyl sulfoxide at 110 degrees C for 15min, following by HPLC purification. Non clinical safety tests were performed for the extended single-dose toxicity study in rats, and for the in vitro metabolite analysis with human liver microsomal incubation. RESULTS: High quality batches of [(18)F]1, compatible with clinical applications, were obtained. At the end of irradiation, the decay-corrected radiochemical yield of [(18)F]1 using 1 and 5mg of precursor based on [(18)F]fluoride was 18.5+/-7.9% (n=10) and 52.0+/-5.8% (n=3), respectively. A single-dose of [(18)F]1 did not show toxicological effects for 14 days after the injection in male and female rats. In human liver microsomal incubations, [(18)F]1 was easily metabolized to [(18)F]desbenzyl-FEDAC ([(18)F]10) by CYPs (4.2% of parent compound left 60min after incubation). CONCLUSION: We successfully synthesized clinical grade batches of [(18)F]1 and verified the absence of innocuity of this radiotracer. [(18)F]1 will be used to first-in-human studies in our facility. PMID- 27183467 TI - Quantum Calculations Indicate Effective Electron Transfer between FMN and Benzoquinone in a New Crystal Structure of Escherichia coli WrbA. AB - Quantum mechanical calculations using the Marcus equation are applied to compare the electron-transfer probability for two distinct crystal structures of the Escherichia coli protein WrbA, an FMN-dependent NAD(P)H: quinone oxidoreductase, with the bound substrate benzoquinone. The calculations indicate that the position of benzoquinone in a new structure reported here and solved at 1.33 A resolution is more likely to be relevant for the physiological reaction of WrbA than a previously reported crystal structure in which benzoquinone is shifted by ~5 A. Because the true electron-acceptor substrate for WrbA is not yet known, the present results can serve to constrain computational docking attempts with potential substrates that may aid in identifying the natural substrate(s) and physiological role(s) of this enzyme. The approach used here highlights a role for quantum mechanical calculations in the interpretation of protein crystal structures. PMID- 27183468 TI - Renal Palliative Care Studies: Coming of Age. PMID- 27183469 TI - Oncogenic mTOR signalling recruits myeloid-derived suppressor cells to promote tumour initiation. AB - Myeloid-derived suppressor cells (MDSCs) play critical roles in primary and metastatic cancer progression. MDSC regulation is widely variable even among patients harbouring the same type of malignancy, and the mechanisms governing such heterogeneity are largely unknown. Here, integrating human tumour genomics and syngeneic mammary tumour models, we demonstrate that mTOR signalling in cancer cells dictates a mammary tumour's ability to stimulate MDSC accumulation through regulating G-CSF. Inhibiting this pathway or its activators (for example, FGFR) impairs tumour progression, which is partially rescued by restoring MDSCs or G-CSF. Tumour-initiating cells (TICs) exhibit elevated G-CSF. MDSCs reciprocally increase TIC frequency through activating Notch in tumour cells, forming a feedforward loop. Analyses of primary breast cancers and patient derived xenografts corroborate these mechanisms in patients. These findings establish a non-canonical oncogenic role of mTOR signalling in recruiting pro tumorigenic MDSCs and show how defined cancer subsets may evolve to promote and depend on a distinct immune microenvironment. PMID- 27183471 TI - Defining the cellular lineage hierarchy in the interfollicular epidermis of adult skin. AB - The interfollicular epidermis regenerates from heterogeneous basal skin cell populations that divide at different rates. It has previously been presumed that infrequently dividing basal cells known as label-retaining cells (LRCs) are stem cells, whereas non-LRCs are short-lived progenitors. Here we employ the H2B-GFP pulse-chase system in adult mouse skin and find that epidermal LRCs and non-LRCs are molecularly distinct and can be differentiated by Dlx1(CreER) and Slc1a3(CreER) genetic marking, respectively. Long-term lineage tracing and mathematical modelling of H2B-GFP dilution data show that LRCs and non-LRCs constitute two distinct stem cell populations with different patterns of proliferation, differentiation and upward cellular transport. During homeostasis, these populations are enriched in spatially distinct skin territories and can preferentially produce unique differentiated lineages. On wounding or selective killing, they can temporarily replenish each other's territory. These two discrete interfollicular stem cell populations are functionally interchangeable and intrinsically well adapted to thrive in distinct skin environments. PMID- 27183472 TI - Sorption selectivity of birnessite particle edges: a d-PDF analysis of Cd(ii) and Pb(ii) sorption by delta-MnO2 and ferrihydrite. AB - Birnessite minerals (layer-type MnO2), which bear both internal (cation vacancies) and external (particle edges) metal sorption sites, are important sinks of contaminants in soils and sediments. Although the particle edges of birnessite minerals often dominate the total reactive surface area, especially in the case of nanoscale crystallites, the metal sorption reactivity of birnessite particle edges remains elusive. In this study, we investigated the sorption selectivity of birnessite particle edges by combining Cd(ii) and Pb(ii) adsorption isotherms at pH 5.5 with surface structural characterization by differential pair distribution function (d-PDF) analysis. We compared the sorption reactivity of delta-MnO2 to that of the nanomineral, 2-line ferrihydrite, which exhibits only external surface sites. Our results show that, whereas Cd(ii) and Pb(ii) both bind to birnessite layer vacancies, only Pb(ii) binds extensively to birnessite particle edges. For ferrihydrite, significant Pb(ii) adsorption to external sites was observed (roughly 20 mol%), whereas Cd(ii) sorption was negligible. These results are supported by bond valence calculations that show comparable degrees of saturation of oxygen atoms on birnessite and ferrihydrite particle edges. Therefore, we propose that the sorption selectivity of birnessite edges follows the same order of that reported previously for ferrihydrite: Ca(ii) < Cd(ii) < Ni(ii) < Zn(ii) < Cu(ii) < Pb(ii). PMID- 27183470 TI - Medial HOXA genes demarcate haematopoietic stem cell fate during human development. AB - Pluripotent stem cells (PSCs) may provide a potential source of haematopoietic stem/progenitor cells (HSPCs) for transplantation; however, unknown molecular barriers prevent the self-renewal of PSC-HSPCs. Using two-step differentiation, human embryonic stem cells (hESCs) differentiated in vitro into multipotent haematopoietic cells that had the CD34(+)CD38(-/lo)CD90(+)CD45(+)GPI-80(+) fetal liver (FL) HSPC immunophenotype, but exhibited poor expansion potential and engraftment ability. Transcriptome analysis of immunophenotypic hESC-HSPCs revealed that, despite their molecular resemblance to FL-HSPCs, medial HOXA genes remained suppressed. Knockdown of HOXA7 disrupted FL-HSPC function and caused transcriptome dysregulation that resembled hESC-derived progenitors. Overexpression of medial HOXA genes prolonged FL-HSPC maintenance but was insufficient to confer self-renewal to hESC-HSPCs. Stimulation of retinoic acid signalling during endothelial-to-haematopoietic transition induced the HOXA cluster and other HSC/definitive haemogenic endothelium genes, and prolonged HSPC maintenance in culture. Thus, medial HOXA gene expression induced by retinoic acid signalling marks the establishment of the definitive HSPC fate and controls HSPC identity and function. PMID- 27183475 TI - Curbing Firearm Violence: Identifying a Specific Target for Physician Action. PMID- 27183476 TI - Linear verrucous epidermal nevi-effects of carbon dioxide laser therapy. AB - Linear epidermal nevus is a congenital malformation characterized by linear, often one-sided arrangement. The lesions are localized along the Blaschko's lines, are present at birth, or appear in early childhood. They can be single or multiple, and have various colors-from skin color to dark brown. These lesions persist through the whole life making a significant cosmetic defect. Here, we present three clinical cases of epidermal nevus treated with CO2 laser. In a female patient, verrucous, dark brown skin eruptions were observed at the back of earlobe and down the neck. In the cases of the male patients, the lesions were located in the area of the neck and left blade. The removal of nevi was performed in stages, by cutting and evaporation using a CO2 laser. A very good therapeutic effect was obtained. CO2 laser treatment is the method of choice for the removal of extensive epidermal nevi. It is characterized by high efficacy and safety. PMID- 27183474 TI - Selection of Amikacin Hyper-Resistant Pseudomonas aeruginosa After Stepwise Exposure to High Amikacin Concentrations. AB - Aerosolized amikacin reaches high concentrations in lung fluids, which are well above the minimum inhibitory concentrations (MICs) of resistant strains of Pseudomonas aeruginosa. However, P. aeruginosa can gain resistance to amikacin through different cumulative mechanisms; amikacin MICs are seldom reported beyond values of 1,000 MUg/ml, as tested in clinical microbiology assays. To assess how high amikacin MICs can be reached by graded exposure, four amikacin-resistant P. aeruginosa isolates were grown in a 4-step increased exposure to amikacin; derivative strains were further characterized by measuring their comparative growth rate, biofilm-forming ability, and susceptibility to other antibiotics. In addition, the mechanism underlying the MIC increase was assessed phenotypically, using a set of 12 aminoglycoside disks, and measuring the effect of Phe-Arg-beta naphthylamide, an efflux pump inhibitor. Graded exposure to amikacin increased MICs of resistant strains up to 10,000-20,000 MUg/ml, without apparent fitness cost, and having variable consequences on their biofilm-forming ability, and on their susceptibility to other antibiotics. Decreased permeability may have contributed to hyper-resistance, although evidence was inconclusive and variable between strains. Amikacin-resistant P. aeruginosa is able to gain in vitro hyper resistance with minimal changes in the specific phenotypes that were tested; the ability to achieve high-level amikacin (AMK) resistance may confound the clinical utility of this aerosolized AMK, but clinical data would be required to assess this. PMID- 27183473 TI - Stem Cells in the Trabecular Meshwork for Regulating Intraocular Pressure. AB - Intraocular pressure (IOP) is still the main treatment target for glaucoma. Outflow resistance mainly exists at the trabecular meshwork (TM) outflow pathway, which is responsible for IOP regulation. Changes of TM cellularity and TM extracellular matrix turnover may play important roles in IOP regulation. In this article, we review basic anatomy and physiology of the outflow pathway and TM stem cell characteristics regarding the location, isolation, identification and function. TM stem cells are localized at the insert region of the TM and are label-retaining in vivo. They can be isolated by side-population cell sorting, cloning culture, or sphere culture. TM stem cells are multipotent with the ability to home to the TM region and differentiate into TM cells in vivo. Other stem cell types, such as adipose-derived stem cells, mesenchymal stem cells and induced pluripotent stem cells have been discovered for TM cell differentiation and TM regeneration. We also review glaucomatous animal models, which are suitable to study stem cell-based therapies for TM regeneration. PMID- 27183477 TI - State of knowledge about energy development impacts on North American rangelands: An integrative approach. AB - To reduce dependence on foreign oil reserves, there has been a push in North America to develop alternative domestic energy resources. Relatively undeveloped renewable energy resources include biofuels and wind and solar energy, many of which occur predominantly on rangelands. Rangelands are also key areas for natural gas development from shales and tight sand formations. Accordingly, policies aimed at greater energy independence are likely to affect the delivery of crucial ecosystem services provided by rangelands. Assessing and dealing with the biophysical and socio-economic effects of energy development on rangeland ecosystems require an integrative and systematic approach that is predicated on a broad understanding of diverse issues related to energy development. In this article, we present a road map for developing an integrative assessment of energy development on rangelands in North America. We summarize current knowledge of socio-economic and biophysical aspects of rangeland based energy development, and we identify knowledge gaps and monitoring indicators to fill these knowledge gaps. PMID- 27183490 TI - Photo-induced green synthesis and antimicrobial efficacy of poly (E caprolactone)/curcumin/grape leaf extract-silver hybrid nanoparticles. AB - This study reports the photo-induced green synthesis and antimicrobial assessment of poly(E-caprolactone)/curcumin/grape leaf extract-Ag hybrid nanoparticles (PCL/Cur/GLE-Ag NPs). PCL/Cur/GLE NPs were synthesized via emulsion-solvent evaporation in the presence of PVA as a capping agent, then used as active nano supports for the green synthesis and stabilization of AgNPs on their surfaces. Both Cur and GLE were selected and incorporated into the PCL nano-supports due to their reported promising antimicrobial activity that would further enhance that of the synthesized AgNPs. The developed PCL/Cur/GLE NPs and PCL/Cur/GLE-Ag hybrid NPs were characterized using UV-visible spectrophotometry, high resolution transmission electron microscopy (HRTEM) and X-ray diffraction (XRD). HRTEM images showed that the PCL/Cur/GLE NPs are monodispersed and spherical with size of about 270nm, and the AgNPs were formed mainly on their surfaces with average size in the range 10-30nm. The synthesized AgNPs were found to be crystalline as shown by XRD patterns with fcc phase oriented along the (111), (200), (220) and (311) planes. The antimicrobial characteristics of the newly developed NPs were investigated against gram-positive and gram-negative bacteria in addition to two fungal strains. The results demonstrated that the PCL/Cur/GLE-Ag hybrid NPs have a potential antimicrobial activity against pathogenic bacterial species and could be considered as an alternative antibacterial agent. PMID- 27183491 TI - Reduced minimum model for the photosynthetic induction processes in photosystem I. AB - Photosystem I (PS I) is one of the most important protein complexes for photosynthesis, which is present in plants, algae and cyanobacteria. A variety of mechanisms for environmental response in and around PS I have been elucidated experimentally and theoretically. During the photosynthetic induction time, the congestion of electron occurs in PS I and then the over-reduced PS I states are realized. This means that the degree of freedom of the redox states of PS I becomes large and thus the understanding of phenomena based on the model describing PS I in the state space becomes difficult. To understand the phenomena intuitively, we have reduced the complicated PS I model which has the multi timescale property for electron and excitation-energy transfer processes into a simple one which has only the mono-timescale property through the use of hierarchical coarse-graining (HCG) method. The coarse-grained model describes the state of PS I by seven variable states, while the original model describes the PS I by 3*2(7)(=384) states. Based on the derived model, the I820 (820nm transmittance signal) curve in photosynthetic induction term, which indicates the accumulations of P700(+) and Pc(+), is simulated and analyzed in comparison with experiment. With respect to this signal curve, it is revealed that the initial increase up to the shoulder at 10(-3) s, the increase from that point to the peak at 2 *10(-2) s, and the decay after that peak reflect the accumulations of P700(+), Pc(+) and P700FA(-)FB(-) (PS I state in which P700,FA(-) and FB(-) are observed.), respectively. Besides, the important role of the charge recombination processes from P700(+)A0A(-) and P700(+)A1A(-) states for the dissipation of the extra absorbed energy in photosynthetic induction period is confirmed. PMID- 27183492 TI - Biophysical studies on the interaction of platinum(II) complex containing antiviral drug ribavirin with human serum albumin. AB - This study describes HSA binding properties of a platinum(II) complex with an antiviral drug ligand; ribavirin. Spectroscopic analysis of the emission quenching at different temperatures and UV-vis spectra revealed that the quenching mechanism of HSA by Pt(II) complex is static quenching mechanism. The binding constants and the number of binding sites were determined by fluorescence quenching method. Pt(II) complex binding is characterized by one high affinity binding site. Through the site marker competitive experiment, site I was assigned to possess high affinity binding site for Pt(II) complex. The calculated thermodynamic parameters (DeltaG, DeltaH and DeltaS) confirmed that the binding reaction is spontaneous, and hydrophobic forces played a major role in the reaction. Fluorescence quenching studies showed that the binding affinity of Pt(II) complex with HSA in the buffer solution at different pH values is: Kb (pH3.0)>Kb (pH9.0)>Kb (pH7.4). The CD spectrum shows the binding of Pt(II) complex leads to a change in the alpha-helical structure of HSA. CD spectroscopy studies further indicated the influence of pH on the complexation process and the alteration in the protein conformation upon binding. PMID- 27183494 TI - Accurate Sample Assignment in a Multiplexed, Ultrasensitive, High-Throughput Sequencing Assay for Minimal Residual Disease. AB - High-throughput sequencing (HTS) (next-generation sequencing) of the rearranged Ig and T-cell receptor genes promises to be less expensive and more sensitive than current methods of monitoring minimal residual disease (MRD) in patients with acute lymphoblastic leukemia. However, the adoption of new approaches by clinical laboratories requires careful evaluation of all potential sources of error and the development of strategies to ensure the highest accuracy. Timely and efficient clinical use of HTS platforms will depend on combining multiple samples (multiplexing) in each sequencing run. Here we examine the Ig heavy-chain gene HTS on the Illumina MiSeq platform for MRD. We identify errors associated with multiplexing that could potentially impact the accuracy of MRD analysis. We optimize a strategy that combines high-purity, sequence-optimized oligonucleotides, dual indexing, and an error-aware demultiplexing approach to minimize errors and maximize sensitivity. We present a probability-based, demultiplexing pipeline Error-Aware Demultiplexer that is suitable for all MiSeq strategies and accurately assigns samples to the correct identifier without excessive loss of data. Finally, using controls quantified by digital PCR, we show that HTS-MRD can accurately detect as few as 1 in 10(6) copies of specific leukemic MRD. PMID- 27183493 TI - Adequately-Sized Nanocarriers Allow Sustained Targeted Drug Delivery to Neointimal Lesions in Rat Arteries. AB - In atherosclerotic lesions, the endothelial barrier against the bloodstream can become compromised, resulting in the exposure of the extracellular matrix (ECM) and intimal cells beneath. In theory, this allows adequately sized nanocarriers in circulation to infiltrate into the intimal lesion intravascularly. We sought to evaluate this possibility using rat carotid arteries with induced neointima. Cy5-labeled polyethylene glycol-conjugated polyion complex (PIC) micelles and vesicles, with diameters of 40, 100, or 200 nm (PICs-40, PICs-100, and PICs-200, respectively) were intravenously administered to rats after injury to the carotid artery using a balloon catheter. High accumulation and long retention of PICs-40 in the induced neointima was confirmed by in vivo imaging, while the accumulation of PICs-100 and PICs-200 was limited, indicating that the size of nanocarriers is a crucial factor for efficient delivery. Furthermore, epirubicin-incorporated polymeric micelles with a diameter similar to that of PICs-40 showed significant curative effects in rats with induced neointima, in terms of lesion size and cell number. Specific and effective drug delivery to pre-existing neointimal lesions was demonstrated with adequate size control of the nanocarriers. We consider that this nanocarrier-based drug delivery system could be utilized for the treatment of atherosclerosis. PMID- 27183495 TI - The relationship between executive functions and IQ in Korean children and the comparison with Chinese children. AB - This study aimed to investigate the relationship between perceived/performance based executive function and IQ. Additionally, the relationship between perceived executive function and intelligence was investigated cross-culturally between South Korea and China. Korean children (60; M = 34, F = 26, Mean age = 10.35) were included in study 1, and Korean children (43, M = 23, F = 20, Mean age = 10.05) and Chinese children (56; M = 29, F = 27, Mean age = 10.40) were included in study 2. The Korean-Wechsler Intelligence Scale for Children-IV, the Stroop test, the CTT-2, and the executive function questionnaire were used for Korean subjects, and the Raven's matrix test and the executive function questionnaire were used for Korean and Chinese subjects. Multiple regression showed that CTT 2(RT), emotional control difficulty, and Color Word within a 45' Stroop test trial were significant predictors of total IQ. The cross-cultural analysis showed a statistically significant difference between the two countries in the emotional control aspect of perceived executive function. There were no interactions between country and intelligence. In conclusion, intelligence was related to overall executive function. Korean children and Chinese children showed cultural differences in processing emotion. These results are expected to contribute to developing therapeutic strategies for executive function in children and to exchanging these strategies between Korea and China. PMID- 27183496 TI - Metadata and Title Correction: Online Focus Group Discussion is a Valid and Feasible Mode When Investigating Sensitive Topics Among Young Persons With a Cancer Experience. AB - [This corrects the article DOI: 10.2196/resprot.5616.]. PMID- 27183497 TI - Risk factors for lymphoedema in women with breast cancer: A large prospective cohort. AB - A prospective study was conducted to identify women at increased risk for lymphoedema (LE) based on axillary surgery. Assessment occurred prior to surgery, within 4 weeks, and at 6, 12 and 18 months following surgery. Following post surgery assessment, women were asked to complete weekly diaries regarding events that occurred in the previous week. Risk factors were grouped into demographic, lifestyle, breast cancer treatment-related, arm swelling-related, and post surgical activities. Bioimpedance spectroscopy thresholds were used to determine presence of LE. At 18-months, 241 women with <5 nodes removed and 209 women with >=5 nodes removed were assessed. For those with <5 nodes removed, LE was present in 3.3% compared with 18.2% for those with >=5 nodes removed. There were insufficient events to identify risk factors for those with <5 nodes removed; for those with >5 nodes removed, independent risk factors included presence of arm swelling at 12-months (Odds Ratio (OR): 13.5, 95% CI 4.8, 38.1; P < 0.01), at 6 months (5.6 (2.0, 16.9); P < 0.01), and radiotherapy to the axilla (2.6 (0.7, 8.9); P = 0.14). Arm swelling at 6 and 12 months was associated with taxane-based chemotherapy, high body weight at diagnosis and arm swelling within 4 weeks post surgery. Of the post-surgical events assessed in a sub-group of women with >5 nodes removed and who maintained weekly diaries, only blood drawn from the 'at risk' arm was identified as a potential risk (OR 2.0; 0.8, 5.2). For women with >=5 nodes removed, arm swelling in the first year poses a very strong risk for presence of LE at 18-months. PMID- 27183498 TI - Multiplexed imaging of intracellular protein networks. AB - Cellular functions emerge from the collective action of a large number of different proteins. Understanding how these protein networks operate requires monitoring their components in intact cells. Due to intercellular and intracellular molecular variability, it is important to monitor simultaneously multiple components at high spatiotemporal resolution. However, inherent trade offs narrow the boundaries of achievable multiplexed imaging. Pushing these boundaries is essential for a better understanding of cellular processes. Here the motivations, challenges and approaches for multiplexed imaging of intracellular protein networks are discussed. (c) 2016 International Society for Advancement of Cytometry. PMID- 27183500 TI - Physician Assistants and Nurse Practitioners in Rural Washington Emergency Departments. AB - One role of physician assistants (PAs) and nurse practitioners (NPs) is to meet the growing demand for access to rural health care. Critical Access Hospitals, those with less than 25 beds, are usually located in rural communities, often providing continuity of care that clinics cannot deliver. Because little is known about staffing in these small hospital emergency departments, an exploratory study was undertaken using a mixed-methods approach. In Washington State, 18 of the 39 Critical Access Hospitals staff their emergency departments with PAs and NPs. Utilization data were collected through structured interviews by phone or in person on site. Most PAs and NPs lived within the community and staffing tended to be either 24 hours in-house or short notice if they lived or worked nearby. Emergency department visits ranged from 200 to 25,000 per year. All sites were designated level V or IV trauma centers and often managed cardiac events, significant injuries and, in some larger settings, obstetrics. In most instances, PAs were the sole providers in the emergency departments, albeit with physician backup and emergency medical technician support if a surge of emergency cases arose. Two-thirds of the PAs had graduated within the last 5 years. Most preferred the autonomy of the emergency department role and all expressed job satisfaction. Geographically, the more remote a Washington State Critical Access Hospital is, the more likely it will be staffed by PAs/NPs. The diverse utilization of semiautonomous PAs and NPs and their rise in rural hospital employment is a new workforce observation that requires broader investigation. PMID- 27183501 TI - Look Carefully: How Learning to Observe Art Can Make Us Better Providers. PMID- 27183499 TI - Transient expression of the diseased phenotype of osteoarthritic chondrocytes in engineered cartilage. AB - Due to the degradation of osteoarthritic (OA) cartilage in post-traumatic OA (PTOA), these tissues are challenging to study and manipulate in vitro. In this study, chondrocytes isolated from either PTOA (meniscal-release (MR) model) or normal (contralateral limb) cartilage of canine knee joints were used to form micropellets to assess the maintenance of the OA chondrocyte phenotype in vitro. Media samples from the micropellet cultures were used to measure matrix metalloproteinase (MMP), chemokine, and cytokine concentrations. Significant differences in matrix synthesis were observed as a function of disease with OA chondrocytes generally synthesizing more extracellular matrix with increasing time in culture. No donor dependent differences were detected. Luminex multiplex analysis of pellet culture media showed disease and time-dependent differences in interleukin (IL)-8, keratinocyte chemoattractant (KC)-like protein, MMP-1, MMP-2, and MMP-3, which are differentially expressed in OA. This memory of their diseased phenotype persists for the first 2 weeks of culture. These results demonstrate the potential to use chondrocytes from an animal model of OA to study phenotype alterations during the progression and treatment of OA. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:829-836, 2017. PMID- 27183502 TI - The role of small bowel capsule endoscopy and ileocolonoscopy in patients with nonspecific but suggestive symptoms of Crohn's disease. AB - OBJECTIVES: Ileocolonoscopy (IC) and small bowel capsule endoscopy (SBCE) are essential tools in the investigation of suspected small bowel Crohn's disease (CD). Overutilization of SBCE should be avoided as it leads to unwanted healthcare expenses; thus, it is recommended when IC is normal and CD is still highly suspected. Our aim was to compare the role of SBCE and IC in the investigation of suspected CD irrespective of its location and assess the additional diagnostic benefit of SBCE over IC. METHODS: This was a retrospective study of 91 patients with chronic abdominal pain and/or diarrhea. All patients were evaluated with both colonoscopy (with terminal ileum intubation where possible) and SBCE. The severity of inflammation on SBCE was assessed using the Lewis Score. Endoscopic findings were analyzed toward CD diagnosis. RESULTS: The sensitivity of IC and SBCE in the diagnosis of either small bowel or colonic CD was 81.82 and 63.64%, whereas the specificity was 77.50 and 92.50%, respectively. Positive and negative predictive value was 33.33 and 96.88% for IC, as well as 53.85 and 94.87% for SBCE. Area under receiver operating characteristic curve was 0.797 for IC and 0.781 for SBCE. IC was superior to SBCE in diagnosing small and large bowel CD. SBCE showed the true extent of CD in one patient missed by IC. It identified lesions suggestive of CD in three patients with normal IC, one of whom was finally diagnosed with CD. CONCLUSION: IC should be the initial diagnostic test in patients with nonspecific, but suggestive symptoms of CD. SBCE offers additional information on small bowel mucosa and disease extent. PMID- 27183503 TI - Genetic diversity of hepatitis B virus (HBV) in Madagascar. AB - Hepatitis B virus (HBV) is a DNA virus belonging to Hepadnaviridae family. Chronic infection with HBV is one major risk factor of hepatic disease. In Madagascar, former studies classified the country as part of high endemic area, as HBV prevalence can reach 23% in general population. However, this prevalence differs largely between urban and rural areas and is estimated to be, respectively, 5% and 26%. The aims of the present study were to describe the genetic diversity of HBV strains from different regions of Madagascar, and to describe the viral gene flow throughout the country by using phylogenetic analysis. This is the first large-scale molecular and phylogenetic study analyzing HBV sequences from 28 different Malagasy areas, never sampled in the past. In this study, the most prevalent genotype/sub-genotypes was E. Migration analysis showed a gene flow from zone 3 (rural) to zone 2 (suburban), and a greater gene flow from the middle part of Madagascar to the north than to the south. It is important to study the HBV infections in Madagascar and to monitor the potential spread of this viral strain inside this country. J. Med. Virol. 88:2138-2144, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27183504 TI - Clinical Significance of Post-Operative Hyperglycemia in Nondiabetic Patients Undergoing Definitive Surgery for Gastrointestinal Fistula. AB - BACKGROUND: To evaluate the association between peri-operative hyperglycemia and adverse events in patients with gastrointestinal (GI) fistulas without a pre operative diagnosis of diabetes mellitus who were undergoing definitive surgery. METHODS: Pre-operative and all post-operative blood glucose concentrations (BG) were retrieved for 363 consecutive patients undergoing GI reconstruction from September 2012 to December 2015. Normoglycemic (BG <125 mL/dL), mild hyperglycemia (125-199 mL/dL), and severe hyperglycemia (>=200 mL/dL) were defined using the highest BG found within the first 48 h post-operatively. Outcomes of interest included 30-d mortality rate and re-operation, time of enteral nutrition resumption, and infectious and non-infectious complications. RESULTS: More than half of the nondiabetic patients (61.4%) experienced hyperglycemia post-operatively. The degree of hyperglycemia correlated with patient age, American Society of Anesthesiologists class, and surgical interventions. Hyperglycemia was associated with re-operation and post-operative complications, the frequency of these complications increasing in parallel with the degree of hyperglycemia. Additionally, post-operative hyperglycemia was associated independently with surgical site infections (p = 0.014), anastomotic leak (p = 0.010), delayed resumption of enteral nutrition (p < 0.001), and longer hospital stay (p < 0.001). CONCLUSION: Elevated post-operative BG was frequent after surgery in patients with GI fistulas. Post-operative hyperglycemia is significantly associated with unfavorable outcomes, and this risk is related to the degree of BG elevation. Our findings suggest that vigilant post-operative BG monitoring and early appropriate glycemic control are critical for patients, even nondiabetic patients, undergoing definitive surgery for GI fistula. PMID- 27183505 TI - Imaging by Zernike phase plates in the TEM. AB - The images produced from simple phase objects, lenses and Zernike phase plates when all have rotational symmetry can be calculated by 1D Fourier-Bessel transforms. For a simple disc object producing a uniform phase shift over its diameter, the resulting image can be defined for any size of object phase change. The monotonic range of intensity variation with object phase is found to depend strongly on the phase change introduced by the phase plate; this property of the system is not well predicted by the weak phase approximation. The effect of spreading the phase transition at the plate over a range of radius is beneficial if the plate phase change is sufficiently small. Weak-phase calculations for a phase distribution more typical of a spherical object are also shown. PMID- 27183506 TI - Energy Drinks and Binge Drinking Predict College Students' Sleep Quantity, Quality, and Tiredness. AB - This study examines whether energy drink use and binge drinking predict sleep quantity, sleep quality, and next-day tiredness among college students. Web-based daily data on substance use and sleep were collected across four semesters in 2009 and 2010 from 667 individuals for up to 56 days each, yielding information on 25,616 person-days. Controlling for average levels of energy drink use and binge drinking (i.e., 4+ drinks for women, 5+ drinks for men), on days when students consumed energy drinks, they reported lower sleep quantity and quality that night, and greater next-day tiredness, compared to days they did not use energy drinks. Similarly, on days when students binge drank, they reported lower sleep quantity and quality that night, and greater next-day tiredness, compared to days they did not binge drink. There was no significant interaction effect between binge drinking and energy drink use on the outcomes. PMID- 27183507 TI - Permethrin-induced oxidative stress and toxicity and metabolism. A review. AB - Permethrin (PER), the most frequently used synthetic Type I pyrethroid insecticide, is widely used in the world because of its high activity as an insecticide and its low mammalian toxicity. It was originally believed that PER exhibited low toxicity on untargeted animals. However, as its use became more extensive worldwide, increasing evidence suggested that PER might have a variety of toxic effects on animals and humans alike, such as neurotoxicity, immunotoxicity, cardiotoxicity, hepatotoxicity, reproductive, genotoxic, and haematotoxic effects, digestive system toxicity, and cytotoxicity. A growing number of studies indicate that oxidative stress played critical roles in the various toxicities associated with PER. To date, almost no review has addressed the toxicity of PER correlated with oxidative stress. The focus of this article is primarily to summarise advances in the research associated with oxidative stress as a potential mechanism for PER-induced toxicity as well as its metabolism. This review summarises the research conducted over the past decade into the reactive oxygen species (ROS) generation and oxidative stress as a consequence of PER treatments, and ultimately their correlation with the toxicity and the metabolism of PER. The metabolism of PER involves various CYP450 enzymes, alcohol or aldehyde dehydrogenases for oxidation and the carboxylesterases for hydrolysis, through which oxidative stress might occur, and such metabolic factors are also reviewed. The protection of a variety of antioxidants against PER-induced toxicity is also discussed, in order to further understand the role of oxidative stress in PER-induced toxicity. This review will throw new light on the critical roles of oxidative stress in PER-induced toxicity, as well as on the blind spots that still exist in the understanding of PER metabolism, the cellular effects in terms of apoptosis and cell signaling pathways, and finally strategies to help to protect against its oxidative damage. PMID- 27183508 TI - [Migration and mental health: new challenges]. AB - Migration is an important risk factor for the development of common and severe mental disorders. Nevertheless, in Europe, immigrants are less likely to access community mental health care and to adhere to treatments, with consequent emergency referrals, involuntary admissions, and traumatic coercive measures. At a clinical level, changes in practices and cross-cultural skills of mental health professionals might be crucial in addressing this challenge. PMID- 27183509 TI - Model of Management (Mo.Ma) for the patient with schizophrenia: crisis control, maintenance, relapse prevention, and recovery with long-acting injectable antipsychotics (LAIs). AB - INTRODUCTION: Schizophrenia is a severe mental disease that affects approximately 1% of the population with a relevant chronic impact on social and occupational functioning and daily activities. People with schizophrenia are 2-2.5 times more likely to die early than the general population. Non-adherence to antipsychotic medications, both in chronic and first episode schizophrenia, is one of the most important risk factors for relapse and hospitalization, that consequently contributes to increased costs due to psychiatric hospitalization. Atypical long acting injectable (LAI) antipsychotics can improve treatment adherence and decrease re-hospitalization rates in patients with schizophrenia since its onset. The primary goals in the management of schizophrenia are directed not only at symptom reduction in the short and long term, but also at maintaining physical and mental functioning, improving quality of life, and promoting patient recovery. AIM: To propose a scientific evidence-based integrated model that provides an algorithm for recovery of patients with schizophrenia and to investigate the effectiveness and safety of antipsychotics LAI in the treatment, maintenance, relapse prevention, and recovery of schizophrenia. METHODS: After an accurate literature review we identified, collected and analyzed the crucial points in taking care schizophrenia patients, through which we defined the steps described in the model of management and the choice of the better treatment option. Results. In the management model we propose, the choice of a second generation long acting antipsychotic, could allow from the earliest stages of illness better patient management, especially for young individuals with schizophrenia onset, a better recovery and significant reductions of relapse and health care costs. LAI formulations of antipsychotics are valuable, because they help patients to remain adherent to their medication through regular contact with healthcare professionals and to prevent covert non-adherence. CONCLUSIONS: The proposed schizophrenia model of management could allow better patient management and recovery, in which the treatment with LAI formulation is a safe and effective therapeutic option. This new therapeutic approach could change the cost structure of schizophrenia by decreasing costs with efficient economic resource allocation guaranteed from efficient diagnostic and therapeutic pathways. PMID- 27183510 TI - Food Addiction: definition, measurement and prevalence in healthy subjects and in patients with eating disorders. AB - The construct of "Food Addiction" (FA) has been introduced in the last decades to better understand abnormal eating patternsin obese and overweight people and in patients with Eating Disorders (EDs). Despite a substantial parallelism between drug addiction and FA, there is still no agreement in considering FA an independent ED or a useful convincing concept. Therefore, the purpose of this review is to aggregate available data, in order to increase knowledge about: 1) definition, measurement and general features of FA; 2) prevalence of FA in clinical and non-clinical samples. Available data suggest that FA seems to be a transnosografic construct and exists in all EDs, with higher prevalence in Bulimia Nervosa. Although the discussion on the autonomous diagnosis of FA within EDs remains open, studies have reported that comorbidity between FA and other EDs is associated with worse clinical conditions and symptoms, justifying, as a result, the usefulness of assessing and treating this condition. PMID- 27183511 TI - [Treatment outcomes of psychiatric rehabilitation: a follow-up study at an italian therapeutic community]. AB - INTRODUCTION: The treatment of severely ill patients with psychotic and personality disorders is often conducted in residential settings such as the Therapeutic Communities (TC). In these facilities a multidisciplinary model is employed to ensure integrative care of the complex psychiatric patient. Although the cost of such programs is very high, evidence of efficacy and effectiveness is scarce, especially in Italy. AIM AND METHODS: Aim of the study is to evaluate the efficacy of TC treatment in a group of patients with severe psychotic and personality disorders. Eighty-one patients have been assessed at baseline and after 6 and 12 months of follow-up in the following areas: global functioning, quality of life, emotion regulation, coping strategies, and insight into illness. RESULTS: At the end of follow-up we could find an improvement in functioning, quality of life, a greater engagement in goal-oriented behaviors, together with a lesser utilization of avoidant coping strategies. However the high dropout rates, which are associated with substance abuse and a diagnosis of personality disorders, should be acknowledged. DISCUSSION AND CONCLUSIONS: The present study reports the efficacy of residential TC treatment for some severely ill patients with psychotic and personality disorders. Strategies aimed at increasing the motivation and preparation of patients before the program begins should be implemented in order to reduce the high dropout rates. PMID- 27183514 TI - [In Process Citation]. PMID- 27183513 TI - Marchiafava-Bignami Disease with frontal cortex involvement and late onset, long lasting psychiatric symptoms: a case report. AB - AIMS: To describe the case and management of a patient with Marchiafava-Bignami Disease (MBD) with frontal cortical lesions, no specific symptom at first referral to the Emergency Room, and late onset of atypical psychiatric symptoms. METHODS: We report the case of a 44-year-old patient with a history of chronic alcohol abuse, eventually diagnosed with MBD. RESULTS: Magnetic Resonance showed lesions in the splenium and the body of corpus callosum and bilateral lesions of the frontal cortex. The patient showed late-onset atypical psychiatricsymptoms which were drug resistant. DISCUSSION: The case we describe seems to support the existing few ones describing cortical involvement in MBD, which suggest that this is associated with a poorer prognosis. Psychiatric symptoms may be challenging to treat because of drug resistance. CONCLUSIONS: The involvement of psychiatrists together with neurologists and radiologists, with a consultation-liaison approach proved important for the achievement of diagnosis and of the most appropriate management and treatment for this patient. PMID- 27183512 TI - Assessment of private security guards by Suicide Probability Scale and Brief Symptom Inventory. AB - AIM: The aim of the present study was to investigate the influence of suicide probability and relevant sociodemographic features and to provide information for preventing suicide in private security guards working under the stressful conditions and continuous exposure to the negative and traumatic life events. METHODS: 200 private security guards and 200 personnels of Ankara University participated in thestudy. A sociodemographic information questionnaire, the Suicide Probability Scale (SPS) and the Brief Symptom Inventory (BSI) were used to collect the data. RESULTS: Gender, marital status, income, religious beliefs, experiencing a life-threatening situation, history of a suicide attempt, smoking and not having a chronic disease caused statistically significant differences in the scores for SPS between the private security guards group and the controls. Moreover there was a statistically significant positive correlation between the total scores of the subscales of SPS and the total scores of BSI. CONCLUSIONS: Like police officers and gendarmes, private security guards are at high risk of committing andattempting suicide because of being at stressful work settings and also suffering from secondary trauma. It is required that they should be aware of their tendency to commit suicide and have regular psychiatric screenings. PMID- 27183515 TI - Identification of nitrate sources in groundwater using a stable isotope and 3DEEM in a landfill in Northeast China. AB - The groundwater was sampled in a typical landfill area of the Northeast China. Coupled stable isotope and three dimensional excitation-emission matrix (3DEEM) were applied to dentify diffused NO3(-) inputs in the groundwater in this area. The results indicated that combined with the feature of groundwater hydrochemistry and three-dimensional fluorescence technology can effectively identify the nitrate pollution sources. The nitrate was derived from manure and sewage by delta(15)N and delta(18)O-NO3(-) values of groundwater in the different periods. The excitation-emission matrix fluorescence spectroscopy was further evidence of groundwater DOM mainly which comes from the landfill. The protein like was very significant at the sampling points near the landfill (SPNL), but only fulvic acid-like appeared at downstream of the landfill groundwater sampling points (DLGSP) in the study area. Partial denitrification processes helped to attenuate nitrate concentration in anaerobic environment. PMID- 27183516 TI - Alternative method of highway traffic safety analysis for developing countries using delphi technique and Bayesian network. AB - Highway traffic accidents all over the world result in more than 1.3 million fatalities annually. An alarming number of these fatalities occurs in developing countries. There are many risk factors that are associated with frequent accidents, heavy loss of lives, and property damage in developing countries. Unfortunately, poor record keeping practices are very difficult obstacle to overcome in striving to obtain a near accurate casualty and safety data. In light of the fact that there are numerous accident causes, any attempts to curb the escalating death and injury rates in developing countries must include the identification of the primary accident causes. This paper, therefore, seeks to show that the Delphi Technique is a suitable alternative method that can be exploited in generating highway traffic accident data through which the major accident causes can be identified. In order to authenticate the technique used, Korea, a country that underwent similar problems when it was in its early stages of development in addition to the availability of excellent highway safety records in its database, is chosen and utilized for this purpose. Validation of the methodology confirms the technique is suitable for application in developing countries. Furthermore, the Delphi Technique, in combination with the Bayesian Network Model, is utilized in modeling highway traffic accidents and forecasting accident rates in the countries of research. PMID- 27183517 TI - Sample-size guidelines for recalibrating crash prediction models: Recommendations for the highway safety manual. AB - The Highway Safety Manual (HSM) prediction models are fitted and validated based on crash data collected from a selected number of states in the United States. Therefore, for a jurisdiction to be able to fully benefit from applying these models, it is necessary to calibrate or recalibrate them to local conditions. The first edition of the HSM recommends calibrating the models using a one-size-fits all sample-size of 30-50 locations with total of at least 100 crashes per year. However, the HSM recommendation is not fully supported by documented studies. The objectives of this paper are consequently: (1) to examine the required sample size based on the characteristics of the data that will be used for the calibration or recalibration process; and, (2) propose revised guidelines. The objectives were accomplished using simulation runs for different scenarios that characterized the sample mean and variance of the data. The simulation results indicate that as the ratio of the standard deviation to the mean (i.e., coefficient of variation) of the crash data increases, a larger sample-size is warranted to fulfill certain levels of accuracy. Taking this observation into account, sample-size guidelines were prepared based on the coefficient of variation of the crash data that are needed for the calibration process. The guidelines were then successfully applied to the two observed datasets. The proposed guidelines can be used for all facility types and both for segment and intersection prediction models. PMID- 27183518 TI - Surveying the Landscape of Ovarian Cancer Research and Care. PMID- 27183519 TI - Antiblastic drug-induced cardiotoxicity and cardioprotection: a compendium. PMID- 27183520 TI - Pathophysiology of cardiotoxicity induced by nonanthracycline chemotherapy. AB - The risk and mechanism of chemotherapy-induced cardiotoxicity (CTX) vary depending on the type and intensity of the anticancer regimen. Myriad chemotherapeutic drugs produce adverse cardiovascular effects such as arterial hypertension, heart failure, and thromboembolic events. Among the numerous classes of these drugs, anthracyclines have been studied most extensively because of their overt cardiovascular effects and the high associated incidence of heart failure. However, CTX might also be caused by other types of chemotherapeutic agents, including alkylating agents (cyclophosphamide, ifosfamide), platinum agents, antimetabolites (5-fluorouracil, capecitabine), antibiotics (mitoxantrone, mitomycin, bleomycin), and antimicrotubule agents (taxanes). Here, we review the incidence, clinical impact, and potential mechanisms of CTX associated with nonanthracycline chemotherapy used for cancer patients. The published data support a marked increase in CTX risk, particularly with certain drugs such as 5-fluorouracil and cisplatin. Each anticancer regimen is associated with distinct modes of heart damage, both symptomatic and asymptomatic. However, the underlying mechanisms of CTX have been established only in a few cases, and only few nonanthracycline chemotherapeutics (mitoxantrone, mitomycin, ifosfamide) act through a recognizable mechanism and show a predictable dose dependence. Lastly, nonanthracycline chemotherapy can induce both chronic lesions, such as systolic dysfunction, and acute lesions, such as the ischemia that occurs within hours or days after treatment. An increased understanding of the incidence, mechanisms, and potential therapeutic targets of CTX induced by various nonanthracycline chemotherapeutic agents is clearly required. PMID- 27183521 TI - Pathophysiology of cardiotoxicity from target therapy and angiogenesis inhibitors. AB - The progress in cancer therapy and the increase in number of long-term survivors reveal the issue of cardiovascular side-effects of anticancer drugs. Cardiotoxicity has become a significant problem, and the risks of adverse cardiac events induced by systemic drugs need to be seriously considered. Potential cardiovascular toxicities linked to anticancer agents include arrhythmias, myocardial ischemia and infarction, hypertension, thromboembolism, left ventricular dysfunction, and heart failure. It has been shown that several anticancer drugs seriously affect the cardiovascular system, such as ErbB2 inhibitors, vascular endothelial growth factor (VEGF) inhibitors, multitargeted kinase inhibitors, Abelson murine leukemia viral oncogene homolog inhibitors, and others. Each of these agents has a different mechanism through which it affects the cardiovascular system. ErbB2 inhibitors block the ErbB4/ErbB2 heterodimerization pathway triggered by Neuregulin-1, which is essential for cardiomyocyte survival. VEGF signaling is crucial for vascular growth, but it also has a major impact on myocardial function, and the VEGF pathway is also essential for maintenance of cardiovascular homeostasis. Drugs that inhibit the VEGF signaling pathway lead to a net reduction in capillary density and loss of contractile function. Here, we review the mechanisms and pathophysiology of the most significant cardiotoxic effects of ErbB2 inhibitors and antiangiogenic drugs. Moreover, we highlight the role of cardioncology in recognizing these toxicities, developing strategies to prevent or minimize cardiovascular toxicity, and reducing long-term cardiotoxic effects. PMID- 27183522 TI - Role of biomarkers in monitoring antiblastic cardiotoxicity. AB - Early detection of anticancer drug-induced cardiotoxicity (CTX) has been evaluated by most international scientific cardiology and oncology societies. High expectations have been placed on the use of specific biomarkers. In recent years, conventional biomarkers and molecules of more recent interest have been tested and compared in the context of anticancer drug-related CTX. Encouraging results were obtained from studies on molecules of myocardial damage, such as troponin and markers of myocardial wall stress, including circulating natriuretic peptides, as well as from the assessment of the products of inflammation or circulating levels of free radicals. However, clear guidelines on their sensitivity, specificity, and accuracy are not yet available, and many challenges, such as the optimal time of assessing, optimal schedule for evaluation, optimal cut-off point for positivity with the highest level of specificity, and optimal comparability of different assays for the measurements, remain unresolved. Given the importance of having a reliable and accurate tool for monitoring anticancer drug-induced CTX, this review will focus on the available data on the most effective and widely used biomarkers and the studies that are currently underway that aim to identify the effectiveness of new approaches in this therapeutic setting. PMID- 27183523 TI - Pathophysiology of anthracycline cardiotoxicity. AB - Anthracyclines (ANTs) are powerful drugs that have reduced the mortality of cancer patients. However, their use is limited by the development of cardiotoxicity (CTX), which is dose dependent and may lead to left ventricular dysfunction and heart failure. Although various strategies have been suggested to reduce the negative effects of ANTs, CTX is still an important unresolved clinical issue. This may be due at least partly to the incomplete characterization of the molecular and cellular mechanisms of ANT-induced CTX. In addition, although various forms of cardiac damage have been demonstrated with the use of these drugs in experimental studies, it is not yet clear how these translate to the clinical setting. Appropriate characterization of potential candidates for ANT-based therapies is essential to decide whether to administer these drugs. Hopefully, new information from genetic profiling will help to identify patients who are at high risk of developing CTX. PMID- 27183524 TI - Cardiovascular imaging in the diagnosis and monitoring of cardiotoxicity: role of echocardiography. AB - The evaluation by cardiovascular imaging of chemotherapy patients became a central topic in the last several years. The use of drugs for the treatment of cancers increased, and new molecules and protocols were developed to improve outcomes in these patients. Although, these novel approaches also produced a progressive increase in side effects, particularly myocardial dysfunction. Imaging of the heart was highly accurate in the early diagnosis of cancer therapeutics related-cardiac dysfunction. Echocardiography is the first-line method to assess ventricular function alterations, and it is required to satisfy the need for an early, easy and accurate diagnosis to stratify the risk of heart failure and manage treatments. A careful monitoring of cardiac function during the course of therapy should prevent the onset of severe heart impairment. This review provides an overview of the most important findings of the role of echocardiography in the management of chemotherapy-treated patients to create a clear and complete description of the efficacy of conventional measurements, the importance of comprehensive heart evaluations, the additional role of new echocardiographic techniques, the utility of integrated studies using other imaging tools and the positions of the most important international societies on this topic. PMID- 27183525 TI - Cardiovascular imaging in the diagnosis and monitoring of cardiotoxicity: cardiovascular magnetic resonance and nuclear cardiology. AB - Chemotherapy-induced cardiotoxicity (CTX) is a determining factor for the quality of life and mortality of patients administered potentially cardiotoxic drugs and in long-term cancer survivors. Therefore, prevention and early detection of CTX are highly desirable, as is the exploration of alternative therapeutic strategies and/or the proposal of potentially cardioprotective treatments. In recent years, cardiovascular imaging has acquired a pivotal role in this setting. Although echocardiography remains the diagnostic method most used to monitor cancer patients, the need for more reliable, reproducible and accurate detection of early chemotherapy-induced CTX has encouraged the introduction of second-line advanced imaging modalities, such as cardiac magnetic resonance (CMR) and nuclear techniques, into the clinical setting. This review of the Working Group on Drug Cardiotoxicity and Cardioprotection of the Italian Society of Cardiology aims to afford an overview of the most important findings from the literature about the role of CMR and nuclear techniques in the management of chemotherapy-treated patients, describe conventional and new parameters for detecting CTX from both diagnostic and prognostic perspectives and provide integrated insight into the role of CMR and nuclear techniques compared with other imaging tools and versus the positions of the most important international societies. PMID- 27183527 TI - Preventing antiblastic drug-related cardiomyopathy: old and new therapeutic strategies. AB - Because of the recent advances in chemotherapeutic protocols, cancer survival has improved significantly, although cardiovascular disease has become a major cause of morbidity and mortality among cancer survivors: in addition to the well-known cardiotoxicity (CTX) from anthracyclines, biologic drugs that target molecules that are active in cancer biology also interfere with cardiovascular homeostasis.Pharmacological and non-pharmacological strategies to protect the cardiovascular structure and function are the best approaches to reducing the prevalence of cardiomyopathy linked to anticancer drugs. Extensive efforts have been devoted to identifying and testing strategies to achieve this end, but little consensus has been reached on a common and shared operability.Timing, dose and mode of chemotherapy administration play a crucial role in the development of acute or late myocardial dysfunction. Primary prevention initiatives cover a wide area that ranges from conventional heart failure drugs, such as beta-blockers and renin-angiotensin-aldosterone system antagonists to nutritional supplementation and physical training. Additional studies on the pathophysiology and cellular mechanisms of anticancer-drug-related CTX will enable the introduction of novel therapies.We present various typologies of prevention strategies, describing the approaches that have already been used and those that could be effective on the basis of a better understanding of pharmacokinetic and pharmacodynamic CTX mechanisms. PMID- 27183526 TI - Cardiotoxicity from anthracycline and cardioprotection in paediatric cancer patients. AB - Notwithstanding the steady progress in survival rates of children and adolescents suffering from cancer, the benefits associated with chemotherapy do not come without risks involving multiple organs and systems, including the cardiovascular apparatus. Anthracyclines-often administered in combination with radiation therapy and/or surgery-are the most used chemotherapeutic compounds in order to treat tumours and blood malignancies even in paediatric age. Being an important side-effect of anthracyclines, carduitoxicity may limit their efficacy during the treatment and induce long-term sequelae, observed even many years after therapy completion. The purpose of this review was to perform an overview about all the possible strategies to prevent and/or limit the anthracyclines adverse side effects for the cardiovascular system in childhood cancer survivors. PMID- 27183528 TI - Novel insights in pathophysiology of antiblastic drugs-induced cardiotoxicity and cardioprotection. AB - Despite advances in supportive and protective therapy for myocardial function, heart failure caused by various clinical conditions, including cardiomyopathy due to antineoplastic therapy, remains a major cause of morbidity and mortality. Because of the limitations associated with current therapies, investigators have been searching for alternative treatments that can effectively repair the damaged heart and permanently restore its function. Damage to the heart can result from both traditional chemotherapeutic agents, such as anthracyclines, and new targeted therapies, such as trastuzumab. Because of this unresolved issue, investigators are searching for alternative therapeutic strategies. In this article, we present state-of-the-art technology with regard to the genomic and epigenetic mechanisms underlying cardiotoxicity and cardioprotection, the role of anticancer in influencing the redox (reduction/oxidation) balance and the function of stem cells in the repair/regeneration of the adult heart. These findings, although not immediately transferable to clinical applications, form the basis for the development of personalized medicine based on the prevention of cardiotoxicity with the use of genetic testing. Proteomics, metabolomics and investigations on reactive oxygen species-dependent pathways, particularly those that interact with the production of NO and energy metabolism, appear to be promising for the identification of early markers of cardiotoxicity and for the development of cardioprotective agents. Finally, autologous cardiac stem and progenitor cells may represent future contributions in the field of myocardial protection and recovery in the context of antiblastic therapy. PMID- 27183531 TI - Acute Myeloblastic Leukemia in the Elderly: How Could Palliative Care Teams and Hematologists Better Work Together? PMID- 27183529 TI - A recommended practical approach to the management of anthracycline-based chemotherapy cardiotoxicity: an opinion paper of the working group on drug cardiotoxicity and cardioprotection, Italian Society of Cardiology. AB - Anthracyclines are the mainstay of treatment of a variety of haematological malignancies and solid tumours. Unfortunately, the clinical use of these drugs is limited by cumulative, dose-related cardiotoxicity which may ultimately lead to a severe and irreversible form of cardiomyopathy. Thus, there is an increasing need for close cooperation among cardiologists, oncologists and haemato-oncologists. As anthracyclines save lives, the logical goal of this cooperation, besides preventing or mitigating cardiotoxicity, is to promote an acceptable balance between the potential cardiac side effects and the vital benefit of anticancer treatment. This manuscript, which is specifically addressed to the cardiologist who has not accumulated much experience in the field of cancer therapy, focuses on several topics, that is old and new mechanisms of cardiac toxicity, late cardiac toxicity, the importance of overall risk assessment, the key role of a cardiology consult before starting cancer therapy, and the pros and cons of primary and secondary prevention programmes. PMID- 27183530 TI - A recommended practical approach to the management of target therapy and angiogenesis inhibitors cardiotoxicity: an opinion paper of the working group on drug cardiotoxicity and cardioprotection, Italian Society of Cardiology. AB - The US National Cancer Institute estimates that cardiotoxicity (CTX) from target therapy refers mostly to four groups of drugs: epidermal growth factor receptor 2 inhibitors, angiogenic inhibitors, directed Abelson murine leukemia viral oncogene homolog inhibitors, and proteasome inhibitors. The main cardiotoxic side effects related to antiepidermal growth factor receptor 2 therapy are left ventricular systolic dysfunction and heart failure. Angiogenesis inhibitors are associated with hypertension, left ventricular dysfunction/heart failure, myocardial ischemia, QT prolongation, and thrombosis. Moreover, other agents may be related to CTX induced by treatment. In this study, we review the guidelines for a practical approach for the management of CTX in patients under anticancer target therapy. PMID- 27183532 TI - Health Status and Risk Behaviors of Sexual Minorities Among Chinese Adolescents: A School-Based Survey. AB - This study aimed to examine the association between sexual orientation and health disparities among a stratified random sample of 3776 secondary students in Hong Kong. The prevalence of homosexuality and bisexuality were 1.5% and 2.6% in boys and 1.8% and 3.7% in girls, respectively. A total of 10.7% of boys and 8.8% of girls were unsure of their sexual orientation. Homosexual and bisexual boys reported poorer physical and mental health than their heterosexual peers. Homosexual and bisexual boys were more likely to engage in smoking, frequent drinking, and vaginal sex and be subjected to sexually transmitted disease and sexual victimization. However, lesbian and bisexual girls were less likely to engage in risky health behaviors except for smoking and being subjected to sexual victimization. There is a gender-specific problem that may warrant prevention and intervention programs to address the unique health issues facing homosexual and bisexual adolescents in Hong Kong. PMID- 27183533 TI - The "Black Box" of Racial Disparities in Asthma. PMID- 27183534 TI - Hydrogen sulfide activates TRPA1 and releases 5-HT from epithelioid cells of the chicken thoracic aorta. AB - Epithelioid cells in the chicken thoracic aorta are chemoreceptor cells that release 5-HT in response to hypoxia. It is likely that these cells play a role in chemoreception similar to that of glomus cells in the carotid bodies of mammals. Recently, H2S was reported to be a key mediator of carotid glomus cell responses to hypoxia. The aim of the present study was to reveal the mechanism of action of H2S on 5-HT outflow from chemoreceptor cells in the chicken thoracic aorta. The 5 HT outflow induced by NaHS, an H2S donor, and Na2S3, a polysulfide, was measured by using a HPLC equipped with an electrochemical detector. NaHS (0.3-3mM) caused a concentration-dependent increase in 5-HT outflow, which was significantly inhibited by the removal of extracellular Ca(2+). 5-HT outflow induced by NaHS (0.3mM) was also significantly inhibited by voltage-dependent L- and N-type Ca(2+) channel blockers and a selective TRPA1 channel blocker. Cinnamaldehyde, a TRPA1 agonist, mimicked the secretory response to H2S. 5-HT outflow induced by Na2S3 (10MUM) was also inhibited by the TRPA1 channel blocker. Furthermore, the expression of TRPA1 was localized to 5-HT-containing chemoreceptor cells in the aortic wall. These findings suggest that the activation of TRPA1 and voltage dependent Ca(2+) channels is involved in H2S-evoked 5-HT release from chemoreceptor cells in the chicken aorta. PMID- 27183535 TI - Fast generation model of high density surface EMG signals in a cylindrical conductor volume. AB - In the course of the last decade, fast and qualitative computing power developments have undoubtedly permitted for a better and more realistic modeling of complex physiological processes. Due to this favorable environment, a fast, generic and reliable model for high density surface electromyographic (HD-sEMG) signal generation with a multilayered cylindrical description of the volume conductor is presented in this study. Its main peculiarity lies in the generation of a high resolution potential map over the skin related to active Motor Units (MUs). Indeed, the analytical calculus is fully performed in the frequency domain. HD-sEMG signals are obtained by surfacic numerical integration of the generated high resolution potential map following a variety of electrode shapes. The suggested model is implemented using parallel computing techniques as well as by using an object-oriented approach which is comprehensive enough to be fairly quickly understood, used and potentially upgraded. To illustrate the model abilities, several simulation analyses are put forward in the results section. These simulations have been performed on the same muscle anatomy while varying the number of processes in order to show significant speed improvement. Accuracy of the numerical integration method, illustrating electrode shape diversity, is also investigated in comparison to analytical transfer functions definition. An additional section provides an insight on the volume detection of a circular electrode according to its radius. Furthermore, a large scale simulation is introduced with 300MUs in the muscle and a HD-sEMG electrode grid composed of 16*16 electrodes for three constant isometric contractions in 12s. Finally, advantages and limitations of the proposed model are discussed with a focus on perspective works. PMID- 27183536 TI - A longitudinal study of self-control at the transition to secondary school: Considering the role of pubertal status and parenting. AB - Higher self-control in children and adolescents is associated with a range of positive outcomes in adulthood. However, little is known about the naturalistic development of self-control during early adolescence and the factors that affect this. We examined the role of puberty and parenting style as theoretically important influences on stability and change in self-control. A longitudinal (3 waves), multiple-informant dataset of children entering early adolescence (M = 11 years) was used to explore longitudinal change in self-control using latent growth curve modelling. Children's self-control declined during the one-year study period and declines were associated with children's behavioural and social functioning. Associations with self-control were found for pubertal status and parental warmth and hostility, but not for parental discipline. The findings suggest that during early adolescence, when children make the transition to secondary school, self-control declines. This is particularly the case for those experiencing puberty earlier than their peers. Parent warmth influences the trajectory of self-control during this period. PMID- 27183537 TI - The Impact of an Ostomy on the Sexual Lives of Persons With Stomas: A Phenomenological Study. AB - PURPOSE: The purpose of this study was to describe the lived experiences of persons with stomas related to sexual function and perceptions and their expectations of the ostomy nurses who care for them. DESIGN: Qualitative, phenomenological study. SUBJECTS AND SETTING: Fourteen persons living with an ostomy for least 2 months participated in the study. Data collection occurred at the ostomy and wound care unit at Dokuz Eylul University Hospital in Izmir, Turkey. METHODS: Data were collected using an in-depth interview method. Interviews lasted from 20 to 60 minutes and were audiotaped. These recordings were transcribed and subjected to content analysis. RESULTS: Five themes emerged from the unstructured interviews: (1) changes in sexual life; (2) changes in body image; (3) fear and anxiety experienced during sexual intercourse; (4) psychological impact of sexual problems; and (5) expectations concerning sexual counseling from ostomy nurses. CONCLUSIONS: Study findings suggest that persons with ostomies experience changes in their body image, along with a decrease in sexual desire. Respondents described avoiding sexual intercourse, and abstained from sleeping with their partners. Male respondents described erectile dysfunction, and female respondents reported pain during sexual intercourse (dyspareunia). Participants stated that they did not feel adequately informed about these problems and desired to receive more information and support from ostomy nurses regarding sexual issues. Based on these findings, we recommend that ostomy nurses provide more counseling concerning sexual function and challenges following ostomy surgery. PMID- 27183538 TI - In Vivo Dual Fluorescence Imaging to Detect Joint Destruction. AB - Diagnosis of cartilage damage in early stages of arthritis is vital to impede the progression of disease. In this regard, considerable progress has been made in near-infrared fluorescence (NIRF) optical imaging technique. Arthritis can develop due to various mechanisms but one of the main contributors is the production of matrix metalloproteinases (MMPs), enzymes that can degrade components of the extracellular matrix. Especially, MMP-1 and MMP-13 have main roles in rheumatoid arthritis and osteoarthritis because they enhance collagen degradation in the process of arthritis. We present here a novel NIRF imaging strategy that can be used to determine the activity of MMPs and cartilage damage simultaneously by detection of exposed type II collagen in cartilage tissue. In this study, retro-orbital injection of mixed fluorescent dyes, MMPSense 750 FAST (MMP750) dye and Alexa Fluor 680 conjugated monoclonal mouse antibody immune reactive to type II collagen, was administered in the arthritic mice. Both dyes were detected with different intensity according to degree of joint destruction in the animal. Thus, our dual fluorescence imaging method can be used to detect cartilage damage as well as MMP activity simultaneously in early stage arthritis. PMID- 27183539 TI - 13th Congress of the European Society for Pediatric Dermatology (ESPD), May 26 28, Paris, France at Maison de la Mutualite. PMID- 27183541 TI - Laboratory diagnosis of thalassemia. AB - The thalassemias can be defined as alpha- or beta-thalassemias depending on the defective globin chain and on the underlying molecular defects. The recognition of carriers is possible by hematological tests. Both alpha- and beta-thalassemia carriers (heterozygotes) present with microcytic hypochromic parameters with or without mild anemia. Red cell indices and morphology followed by separation and measurement of Hb fractions are the basis for identification of carriers. In addition, iron status should be ascertained by ferritin or zinc protoporphyrin measurements and the iron/total iron-binding capacity/saturation index. Mean corpuscular volume and mean corpuscular hemoglobin are markedly reduced (mean corpuscular volume: 60-70 fl; MCH: 19-23 pg) in beta-thalassemia carriers, whereas a slight to relevant reduction is usually observed in alpha-carriers. HbA2 determination is the most decisive test for beta-carrier detection although it can be disturbed by the presence of delta-thalassemia defects. In alpha thalassemia, HbA2 can be lower than normal and it assumes significant value when iron deficiency is excluded. Several algorithms have been introduced to discriminate from thalassemia carriers and subjects with iron-deficient anemia; because the only discriminating parameter is the red cell counts, these formulas must be used consciously. Molecular analysis is not required to confirm the diagnosis of beta-carrier, but it is necessary to confirm the alpha-thalassemia carrier status. The molecular diagnosis is essential to predict severe transfusion-dependent and intermediate-to-mild non-transfusion-dependent cases. DNA analysis on chorionic villi is the approach for prenatal diagnosis and the methods are the same used for mutations detection, according to the laboratory facilities and expertise. PMID- 27183540 TI - Prevalence, virulence and antibiotic susceptibility of Salmonella spp. strains, isolated from beef in Greater Tunis (Tunisia). AB - The aim of this work was to investigate the presence of Salmonella spp. in 300 beef meat samples collected from cattle carcasses of different categories (young bulls, culled heifers and culled cows). The detection of Salmonella spp. was performed by the alternative VIDAS Easy Salmonella technique and confirmed by PCR using Salmonella specific primers. Salmonella serotypes were determined by slide agglutination tests. The resistance to 12 antibiotics was determined by the diffusion method on Mueller-Hinton agar antibiotic discs. The overall contamination rate of beef by Salmonella spp. was 5.7% (17/300). This rate varied from naught (0/100) in bulls' meat to 14% (14/100) in culled cows' meat (p<0.001). The prevalence of Salmonella spp. was higher in summer and in cattle with digestive disorders: chronic gastroenteritis (6/17), traumatic peritonitis (3/17) and intestinal obstruction (2/17) (p<0.0001). Of the 17 Salmonella isolates, 6 serotypes were identified, namely Salmonella Montevideo (8/17), Salmonella Anatum (3/17), Salmonella Minnesota (2/17), Salmonella Amsterdam (2/17), Salmonella Kentucky (1/17) and Salmonella Brandenburg (1/17) (p<0.05). Unlike other serotypes, S. Montevideo was present during the whole year except winter. Almost all of the strains (16/17) were resistant to at least one of the 12 tested antibiotics. Multidrug-resistance concerned 14/17 of the strains, including Amoxicillin (13/17), Tetracycline (12/17), Streptomycin (10/17) and Nalidixic acid (6/17). All the strains were sensitive to the association (Amoxicillin+Clavulanic acid), Cefoxitin and Ceftazidime. In addition, our study showed that all Salmonella strains (17) were positive for invasion gene invA and negative for the virulence gene spvC. Only one isolate (S. Kentucky) harbored the h-li virulence gene. PMID- 27183542 TI - Retinal Toxicity Associated With MEK Inhibitor Use for Metastatic Cancer: A Rising Trend in Ophthalmology. PMID- 27183543 TI - Focal Nonperfusion of Deep Retinal Capillary Plexus in Eyes With Epiretinal Membranes Revealed by Optical Coherence Tomography Angiography. AB - BACKGROUND AND OBJECTIVE: To evaluate the leakage pattern in eyes with idiopathic epiretinal membranes (ERM) using fluorescein angiography (FA) and the structure of the retinal capillary plexus with optical coherence tomography angiography (OCTA). PATIENTS AND METHODS: The authors enrolled patients with idiopathic macular ERM in the consecutive case series study. All patients were evaluated using FA at the central macula area and OCTA at the central 3 mm * 3 mm. RESULTS: Six patients (seven eyes) with ERM completed this preliminary study. The authors examined five eyes that showed increased macular thickness without a lamellar hole and two eyes that showed combined ERM with a lamellar hole. In the five eyes with ERM alone, the irregular focal hypofluorescent areas in FA corresponded to the locations of absent or low flow signals within vasculatures in the deep retinal capillary plexus seen in OCTA, whereas most of the superficial retinal capillary plexus was not affected, except vascular tortuosity in OCTA. In the two eyes combined with lamellar hole, OCTA showed central cystic lesions without vasculatures, but no low flow signals within vasculatures in the deep retinal capillary plexus beyond the hole. These focal irregular, absent, or low flow signals within vasculatures in the deep retinal plexus improved 1 month after surgical removal of the ERM in one eye. CONCLUSION: Mechanical stress exerted from the ERM might affect deep retinal capillary flow more profoundly than the superficial capillary flow, which would account for the fluorescence changes seen in FA. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:404-409.]. PMID- 27183544 TI - Application of Novel Software Algorithms to Spectral-Domain Optical Coherence Tomography for Automated Detection of Diabetic Retinopathy. AB - BACKGROUND AND OBJECTIVE: To present novel software algorithms applied to spectral-domain optical coherence tomography (SD-OCT) for automated detection of diabetic retinopathy (DR). PATIENTS AND METHODS: Thirty-one diabetic patients (44 eyes) and 18 healthy, nondiabetic controls (20 eyes) who underwent volumetric SD OCT imaging and fundus photography were retrospectively identified. A retina specialist independently graded DR stage. Trained automated software generated a retinal thickness score signifying macular edema and a cluster score signifying microaneurysms and/or hard exudates for each volumetric SD-OCT. RESULTS: Of 44 diabetic eyes, 38 had DR and six eyes did not have DR. Leave-one-out cross validation using a linear discriminant at missed detection/false alarm ratio of 3.00 computed software sensitivity and specificity of 92% and 69%, respectively, for DR detection when compared to clinical assessment. CONCLUSION: Novel software algorithms applied to commercially available SD-OCT can successfully detect DR and may have potential as a viable screening tool for DR in future. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:410-417.]. PMID- 27183545 TI - Quantitative Assessment of Optic Nerve Changes in Patients With Diabetic Macular Edema Treated With Fluocinolone Acetonide Vitreous Implants. AB - BACKGROUND AND OBJECTIVE: To evaluate glaucomatous changes in patients with diabetic macular edema (DME) treated with intravitreal implants releasing 0.2 ug/day or 0.5 ug/day fluocinolone acetonide (FAc) (Iluvien 0.2 ug/day; Alimera Sciences, Alpharetta, GA) or sham control. PATIENTS AND METHODS: Fundus photographs were assessed to determine clinically significant changes in glaucomatous indicators. RESULTS: The mean cup-to-disc ratio (CDR) change was similar with all three treatments. Compared with sham control, a significantly greater proportion of patients treated with 0.5 ug/day but not 0.2 ug/day FAc experienced a CDR increase of greater than 0.1. There was no significant increase in the proportion of patients experiencing a CDR increase of greater than 0.2 with either dose of implant versus sham control. Other indicators of glaucomatous change did not differ significantly with treatment. Subgroup analyses showed no differences in cupping based on ocular or baseline characteristics. CONCLUSION: Treatment with FAc for 36 months was not associated with significant glaucomatous optic nerve head changes in patients with DME with or without increased intraocular pressure. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:418-425.]. PMID- 27183547 TI - Comparative Evaluation of Retinal Nerve Fiber Layer Thickness After Conventional Brilliant Blue Assisted Internal Limiting Membrane Peeling Versus Brilliant Blue Selective Staining Using Whole Blood in Macular Hole Surgery. AB - BACKGROUND AND OBJECTIVE: To evaluate retinal nerve fiber layer (RNFL) thickness after conventional brilliant blue (BB) assisted macular hole (MH) surgery versus BB selective staining using whole blood (WB) in MH surgery. PATIENTS AND METHODS: Sixty eyes with stage 4 idiopathic MH with a clear media were randomly divided into two equal groups. Group A eyes underwent sequential intraoperative use of autologous heparinized WB followed by BB dye for staining internal limiting membrane, whereas eyes in group B were subjected to conventional BB staining. Clinical examination and spectral-domain optical coherence tomography was done preoperatively and postoperatively up to 6 months. RESULTS: Mean global RNFL thickness and mean temporal RNFL thickness decreased in both groups postoperatively, but the reduction in RNFL thickness in group B was greater than group A at all postoperative visits (P < .05). CONCLUSION: BB toxicity may be responsible for reduction of RNFL thickness and WB appears to protect RNFL against dye toxicity. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:436-442.]. PMID- 27183548 TI - Treatment of Coats' Disease With Combination Therapy of Intravitreal Bevacizumab, Laser Photocoagulation, and Sub-Tenon Corticosteroids. AB - BACKGROUND AND OBJECTIVE: The authors investigate the efficacy of combination treatment with laser photocoagulation, intravitreal bevacizumab (IVB) (Avastin; Genentech, South San Francisco, CA), and sub-Tenon corticosteroids in Coats' disease. PATIENTS AND METHODS: Patient records at the Bascom Palmer Eye Institute were reviewed from August 2002 to January 2014. Primary outcome measures were anatomic success, globe salvage, and final visual acuity. RESULTS: Of the 26 patients (26 eyes) reviewed, 20 patients had stage 3A2, four patients had stage 3A1, and two patients had stage 2A. Mean follow-up time was 2.26 years. The median number of applications was five and three for laser and IVB, respectively. Five patients received sub-Tenon triamcinolone injections. Global salvage was achieved in all patients. Final visual acuity outcomes were reasonable: 20/20 to 20/50 in five patients, 20/60 to 20/100 in five patients, and 20/200 or less in 16 patients. CONCLUSION: Intravitreal injections of bevacizumab used in combination with repetitive laser photocoagulation therapy yielded anatomic success, global salvage, and reasonable visual acuity outcomes. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:443-449.]. PMID- 27183546 TI - Characterization of Intraocular Pressure Increases and Management Strategies Following Treatment With Fluocinolone Acetonide Intravitreal Implants in the FAME Trials. AB - BACKGROUND AND OBJECTIVE: To compare elevated intraocular pressure (IOP) management and outcomes among patients with diabetic macular edema who received fluocinolone acetonide (FAc) implants versus sham-control treatment and explore the prior ocular steroid exposure impact on IOP outcomes. PATIENTS AND METHODS: Best-corrected visual acuity (BCVA) was measured using Early Treatment Diabetic Retinopathy Study charts or electronic VA testers. Goldmann applanation tonometry was used to measure IOP. RESULTS: Elevated IOP was more common in FAc-versus sham control-treated patients. Medication, and less often trabeculoplasty or surgery, was used to lower IOP without affecting VA outcomes. No patient treated with 0.2 ug/day FAc who received prior ocular steroid required IOP-lowering surgery. CONCLUSION: Elevated IOP may occur following FAc implant receipt; however, in the present study, it was manageable and did not impact vision outcomes. Patients previously treated with ocular steroid did not require IOP-lowering surgery following 0.2 ug/day FAc implant administration. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:426-435.]. PMID- 27183549 TI - Choroidal Neovascularization Associated With Birdshot Chorioretinopathy. AB - BACKGROUND AND OBJECTIVE: Patients with birdshot chorioretinopathy (BCR) may develop visual compromise due to choroidal neovascularization (CNV), and few series address management strategies in the anti-vascular endothelial growth factor (VEGF) era. The purpose of this study was to describe the clinical outcomes of combination anti-VEGF and immunosuppressive therapy for CNV associated with BCR. PATIENTS AND METHODS: Retrospective, interventional case series. Patients with BCR from two tertiary uveitis and retina practices were reviewed. Patients with CNV in association with BCR were identified and reviewed in detail. Clinical features, treatments utilized (ie, anti-VEGF injections, immunosuppressive therapy), and functional and structural outcomes over long-term follow-up were recorded. Outcomes measured included Snellen visual acuity, spectral-domain optical coherence tomography macular thickness during treatment, number and type of anti-VEGF injections, the need for initiation or escalation of immunosuppression, and incidence of CNV in macula-involved versus macula-sparing BCR. RESULTS: Four of 36 BCR patients were diagnosed with choroidal neovascularization (11%). Identification of CNV in all patients prompted treatment with intravitreal anti-VEGF injections and an increase or initiation of local or systemic immunosuppression. Mean Snellen visual acuity improved from 20/60 to 20/30 at final follow-up (P = .02). Mean central subfield thickness improved from 443 MU to 254 MU (P = .04). CNV in association with BCR occurred at a rate of 0.11 events per patient-year (95% CI, 0.02-0.31) in macula-involved BCR versus zero events/patient-year in macula-spared BCR (95% CI, 0-0.058; P = .009). CONCLUSION: Anti-VEGF therapy was effective for the treatment of CNV in BCR patients. A combination of systemic or local immunosuppression and anti-VEGF therapy may be useful in the management of CNV associated with BCR. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:450-457.]. PMID- 27183550 TI - Factors Associated With Poor Response to Aflibercept After Switching From Ranibizumab or Bevacizumab in Neovascular Age-related Macular Degeneration. AB - BACKGROUND AND OBJECTIVE: The purpose of this study was to analyze demographic and ocular features of patients with age-related macular degeneration who failed aflibercept (Eylea; Regeneron, Tarrytown, NY) treatment after switching from ranibizumab (Lucentis; Genentech, South San Francisco, CA) or bevacizumab (Avastin; Genentech, South San Francisco, CA). PATIENTS AND METHODS: Retrospective chart review of patients treated with aflibercept at the Byers Eye Institute from November 2011 to August 2014. Patient visual acuity was noted prior to aflibercept; after 1, 3, and 12 months; and on the most recent visit. Patients who improved vision after switching were compared to patients who lost vision. Demographic and imaging features were analyzed using univariate and multivariate statistics. RESULTS: Patients who lost vision had significantly higher BMI (P = .013, multivariate) and geographic atrophy (P = .0381, univariate; P = .1, multivariate) compared to patients who improved vision. CONCLUSION: BMI and geographic atrophy may be considered as potential indicators for poor response to aflibercept after switching from ranibizumab or bevacizumab. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:458-465.]. PMID- 27183552 TI - Ultra Wide-Field Indocyanine Green Angiogram Highlights Choroidal Perfusion Delay Secondary to Giant Cell Arteritis. AB - Vision loss in giant cell arteritis (GCA) often presents as anterior ischemic optic neuropathy and central retinal artery occlusion. Previous studies have established an acute delay in choroidal perfusion on fluorescein angiography (FA) as a classic sign of GCA. The authors present a unique imaging case report of GCA where ultra wide-field (UWF) indocyanine green angiography (ICGA) offers improved characterization of delayed choroidal perfusion compared to FA. Routine use of ICGA, particularly UWF imaging, in patients with suspected GCA should be studied in a larger cohort to determine whether it may improve detection of choroidal perfusion delay. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:471-473.]. PMID- 27183551 TI - Spectral-Domain Optical Coherence Tomography Angiography of Central Retinal Artery Occlusion. AB - The authors report the use of optical coherence tomography angiography (OCTA) to determine retinal blood flow in a patient with central retinal artery occlusion (CRAO). Spectral-domain OCTA (SD-OCTA) was performed on an eye with CRAO. En face vascular images were constructed using an optical microangiography algorithm. The retinal vasculature was clearly imaged with high fidelity; areas of perfused retina were identified with exquisite detail. This study supports use of OCTA in diagnosing and monitoring CRAOs. Future research is warranted to recognize full potential of this imaging modality. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:467-470.]. PMID- 27183553 TI - Reduction of Diabetic Macular Edema in the Untreated Fellow Eye Following Intravitreal Injection of Aflibercept. AB - A 59-year-old patient with bilateral worsening diabetic macular edema received intravitreal injection of aflibercept (Eylea; Regeneron, Tarrytown, NY) to the left eye only. On 1-month follow-up, there was noted bilateral improvement of visual acuity and diabetic macular edema on spectral-domain optical coherence tomography imaging, reflecting bilateral effect of unilateral treatment with aflibercept. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:474-476.]. PMID- 27183554 TI - Progressive Release of Vitreomacular Traction With Aflibercept. AB - A patient with combined diabetic macular edema (DME) and vitreomacular traction (VMT) was treated with a series of intravitreal aflibercept (Eylea; Regeneron, Tarrytown, NY) injections. The VMT progressively released during the course of the five intravitreal injections. This release may have been spontaneous, due to a nonspecific mechanical effect from the injections, or due to a pharmacologic effect from the aflibercept. While treating DME, anti-vascular endothelial growth factor agents may have an additional benefit in releasing VMT. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:477-481.]. PMID- 27183555 TI - A Rare Cause of Retinal Artery Occlusion in Severe Hypernatremic Dehydration in Newborns. AB - Neonatal hypernatremia is an important electrolyte disorder that may have serious complications. It may be a rare and underdiagnosed cause of venous and arterial thrombosis, leading to severe brain damage by cerebral edema and intracranial hemorrhage. Here, the authors present a case of bilateral central retinal artery occlusion in a newborn with severe hypernatremic dehydration who is found to be normal in terms of other causes of retinal arterial thromboembolization. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:482-485.]. PMID- 27183556 TI - Expansion of Severely Constricted Visual Field Using Google Glass. AB - Google Glass (Google, Mountain View, CA) is a wearable technology with a computer and camera mounted on an eyeglass frame. The camera captures wide-angle video and projects it onto a prism located in the right superior temporal quadrant of the wearer's visual field. The authors present a case of an individual who used Google Glass' video projection feature to expand his severely constricted right visual field. This patient reported improved ambulatory navigation. Using Google Glass, the patient's peripheral vision, measured using Goldmann kinetic perimetry, expanded impressively. Based on these preliminary results, the authors propose further characterization on the potential utility of such head-mount display technology as a tool to improve the lives of patients with severely constricted visual fields. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:486 489.]. PMID- 27183557 TI - Current Practice Patterns for Treatment of Retinopathy of Prematurity. AB - To evaluate current practice patterns for the treatment of retinopathy of prematurity (ROP) and characterize factors influencing clinical decisions, a database of all ophthalmologists subspecializing in pediatrics and retina was compiled from membership directories of subspecialty societies and academic institutions in the United States. A web-based survey was emailed to these subspecialists to obtain information regarding demographics, treatment practices, and preferences in hypothetical clinical scenarios. From 2,977 retina and pediatric ophthalmology subspecialists surveyed, 302 self-reported as treating ROP, of whom 56% reported having performed intra-vitreal anti-VEGF injection for ROP. Anti-vascular endothelial growth factor (VEGF) injection was the initial treatment for posterior type 1 high risk ROP preferred by the majority of surveyed ROP treaters, whereas 66% reported uncertainty regarding long-term side effects as the largest barrier to its use. Geographic practice location was associated with anti-VEGF use (P = .019). Anti-VEGF injection as ROP therapy was preferred in some scenarios in our sample. Concerns regarding potential anti-VEGF side effects warrant further investigation. CLINICAL IMPLICATIONS: Intravitreal anti-VEGF injection was chosen as the initial therapeutic option by the majority of ROP treatment providers for posterior type 1 ROP in this survey that assessed treatment preferences for a range of clinical scenarios. Uncertainty regarding long-term side effects was the largest reported barrier to use of anti-VEGF for ROP treatment. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:491-495.]. PMID- 27183558 TI - Choroidal Metastases From Cutaneous Melanoma. AB - A 92-year-old man presented with months of progressive blurry vision, worsening acutely in his right eye. He denied pain, diplopia, or photopsias. His history was significant for multiple myeloma, prostate cancer, and malignant melanoma of his right shoulder treated with local excision. He had local recurrence with hepatic metastasis of the melanoma treated with radiation and chemotherapy. On examination, his visual acuity was counting fingers in the right eye and 20/60 in the left eye. Amsler grid testing demonstrated metamorphopsia in the right eye. Fundus exam of the right and left eyes revealed multiple, elevated, pigmented choroidal lesions, with associated subretinal fluid in the right macula. This appearance is consistent with hematogenous metastasis of cutaneous malignant melanoma to the choroid and associated serous fluid-causing metamorphopsia. The patient was enrolled in a clinical trial combining plasmid IL-12 with pembrolizumab (Keytruda; Merck, Whitehouse Station, NJ). He passed away 2 months after initial presentation to our clinic. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:497.]. PMID- 27183559 TI - 8 Questions with OSLIR. PMID- 27183560 TI - Eric Lander and David Botstein on Mapping Quantitative Traits. PMID- 27183561 TI - Meuwissen et al. on Genomic Selection. PMID- 27183562 TI - Genetic Time Travel. AB - At its core, genetics is a historical discipline. Mutations are passed on from generation to generation and accumulate as a result of chance as well as of selection within and between populations and species. However, until recently, geneticists were confined to the study of present-day genetic variation and could only indirectly make inferences about the historical processes that resulted in the variation in present-day gene pools. This "time trap" has now been overcome thanks to the ability to analyze DNA extracted from ancient remains, and this is about to revolutionize several aspects of genetics. PMID- 27183563 TI - Biochemical Genetics and Molecular Biology: The Contributions of George Beadle and Edward Tatum. PMID- 27183564 TI - Sleep and Development in Genetically Tractable Model Organisms. AB - Sleep is widely recognized as essential, but without a clear singular function. Inadequate sleep impairs cognition, metabolism, immune function, and many other processes. Work in genetic model systems has greatly expanded our understanding of basic sleep neurobiology as well as introduced new concepts for why we sleep. Among these is an idea with its roots in human work nearly 50 years old: sleep in early life is crucial for normal brain maturation. Nearly all known species that sleep do so more while immature, and this increased sleep coincides with a period of exuberant synaptogenesis and massive neural circuit remodeling. Adequate sleep also appears critical for normal neurodevelopmental progression. This article describes recent findings regarding molecular and circuit mechanisms of sleep, with a focus on development and the insights garnered from models amenable to detailed genetic analyses. PMID- 27183567 TI - Corrigendum. PMID- 27183570 TI - Unlike in Children with Allergic Asthma, IgE Transcripts from Preschool Children with Atopic Dermatitis Display Signs of Superantigen-Driven Activation. AB - The IgE repertoire in children with asthma reflects an adaptive B cell response, indicative of Ag-driven selection. However, the same might not apply to atopic dermatitis, which is often the first manifestation of atopy. The objective of our present study was to characterize the IgE repertoire of preschool children with atopic dermatitis with regard to signs of superantigen-like activation, clonal relationship, and indications of Ag selection. Total RNA was isolated from PBMCs of five children with atopic dermatitis. IgE transcripts were amplified, cloned, and sequenced using RT-PCR. We obtained 200 functional IgE sequences, which were compared with 1140 sequences from 11 children with asthma. Whereas variable gene segment of the H Ig chain (VH) gene usage in asthma reflected germline distribution, IgE transcripts from children with atopic dermatitis displayed a dominance of the otherwise scarcely expressed VH2 and VH4 family. Whereas IgE transcripts from children with asthma were highly mutated (7.2%), somatic mutation rate in atopic dermatitis was less than half as high (3.4%). Moreover, the proportion of transcripts that were indicative of Ag selection was reduced to 11% in atopic dermatitis (24% in asthma). In summary, IgE repertoires vary significantly between children with different atopic diseases. Compared with children with asthma, IgE transcripts from preschool children with atopic dermatitis are significantly less mutated, clonally less focused, and less indicative of Ag selection. We consider our data reconcilable with the hypothesis that a superantigen-like activation contributes to the maturation and selection of the IgE repertoire in atopic dermatitis. PMID- 27183571 TI - Structures of Preferred Human IgV Genes-Based Protective Antibodies Identify How Conserved Residues Contact Diverse Antigens and Assign Source of Specificity to CDR3 Loop Variation. AB - The human Ab response to certain pathogens is oligoclonal, with preferred IgV genes being used more frequently than others. A pair of such preferred genes, IGVK3-11 and IGVH3-30, contributes to the generation of protective Abs directed against the 23F serotype of the pneumonococcal capsular polysaccharide of Streptococcus pneumoniae and against the AD-2S1 peptide of the gB membrane protein of human CMV. Structural analyses of Fab fragments of mAbs 023.102 and pn132p2C05 in complex with portions of the 23F polysaccharide revealed five germline-encoded residues in contact with the key component, l-rhamnose. In the case of the AD-2S1 peptide, the KE5 Fab fragment complex identified nine germline encoded contact residues. Two of these germline-encoded residues, Arg91L and Trp94L, contact both the l-rhamnose and the AD-2S1 peptide. Comparison of the respective paratopes that bind to carbohydrate and protein reveals that stochastic diversity in both CDR3 loops alone almost exclusively accounts for their divergent specificity. Combined evolutionary pressure by human CMV and the 23F serotype of S. pneumoniae acted on the IGVK3-11 and IGVH3-30 genes as demonstrated by the multiple germline-encoded amino acids that contact both l rhamnose and AD-2S1 peptide. PMID- 27183565 TI - The Caenorhabditis elegans Excretory System: A Model for Tubulogenesis, Cell Fate Specification, and Plasticity. AB - The excretory system of the nematode Caenorhabditis elegans is a superb model of tubular organogenesis involving a minimum of cells. The system consists of just three unicellular tubes (canal, duct, and pore), a secretory gland, and two associated neurons. Just as in more complex organs, cells of the excretory system must first adopt specific identities and then coordinate diverse processes to form tubes of appropriate topology, shape, connectivity, and physiological function. The unicellular topology of excretory tubes, their varied and sometimes complex shapes, and the dynamic reprogramming of cell identity and remodeling of tube connectivity that occur during larval development are particularly fascinating features of this organ. The physiological roles of the excretory system in osmoregulation and other aspects of the animal's life cycle are only beginning to be explored. The cellular mechanisms and molecular pathways used to build and shape excretory tubes appear similar to those used in both unicellular and multicellular tubes in more complex organs, such as the vertebrate vascular system and kidney, making this simple organ system a useful model for understanding disease processes. PMID- 27183569 TI - CD275-Independent IL-17-Producing T Follicular Helper-like Cells in Lymphopenic Autoimmune-Prone Mice. AB - T cells undergo homeostatic expansion and acquire an activated phenotype in lymphopenic microenvironments. Restoration of normal lymphocyte numbers typically re-establishes normal homeostasis, and proinflammatory cytokine production returns to baseline. Mice deficient in guanine nucleotide exchange factor RasGRP1 exhibit dysregulated homeostatic expansion, which manifests as lymphoproliferative disease with autoantibody production. Our previous work revealed that autoreactive B cells lacking RasGRP1 break tolerance early during development, as well as during germinal center responses, suggesting that T cell independent and T cell-dependent mechanisms are responsible. Examination of whether a particular T cell subset is involved in the breach of B cell tolerance revealed increased Th17 cells in Rasgrp1-deficient mice relative to control mice. Rasgrp1-deficient mice lacking IL-17R had fewer germinal centers, and germinal centers that formed contained fewer autoreactive B cells, suggesting that IL-17 signaling is required for a break in B cell tolerance in germinal centers. Interestingly, a fraction of Th17 cells from Rasgrp1-deficient mice were CXCR5(+) and upregulated levels of CD278 coordinate with their appearance in germinal centers, all attributes of T follicular helper cells (Tfh17). To determine whether CD278-CD275 interactions were required for the development of Tfh17 cells and for autoantibody, Rasgrp1-deficient mice were crossed with CD275-deficient mice. Surprisingly, mice deficient in RasGRP1 and CD275 formed Tfh17 cells and germinal centers and produced similar titers of autoantibodies as mice deficient in only RasGRP1. Therefore, these studies suggest that requirements for Tfh cell development change in lymphopenia-associated autoimmune settings. PMID- 27183572 TI - Cutting Edge: IFN-beta Expression in the Spleen Is Restricted to a Subpopulation of Plasmacytoid Dendritic Cells Exhibiting a Specific Immune Modulatory Transcriptome Signature. AB - Type I IFNs are critical in initiating protective antiviral immune responses, and plasmacytoid dendritic cells (pDCs) represent a major source of these cytokines. We show that only few pDCs are capable of producing IFN-beta after virus infection or CpG stimulation. Using IFNbeta/YFP reporter mice, we identify these IFN-beta-producing cells in the spleen as a CCR9(+)CD9(-) pDC subset that is localized exclusively within the T/B cell zones. IFN-beta-producing pDCs exhibit a distinct transcriptome profile, with higher expression of genes encoding cytokines and chemokines, facilitating T cell recruitment and activation. These distinctive characteristics of IFN-beta-producing pDCs are independent of the type I IFNR-mediated feedback loop. Furthermore, IFN-beta-producing pDCs exhibit enhanced CCR7-dependent migratory properties in vitro. Additionally, they effectively recruit T cells in vivo in a peritoneal inflammation model. We define "professional type I IFN-producing cells" as a distinct subset of pDCs specialized in coordinating cellular immune responses. PMID- 27183573 TI - Heme Oxygenase-1 Regulates Inflammation and Mycobacterial Survival in Human Macrophages during Mycobacterium tuberculosis Infection. AB - Mycobacterium tuberculosis, the causative agent of tuberculosis, is responsible for 1.5 million deaths annually. We previously showed that M. tuberculosis infection in mice induces expression of the CO-producing enzyme heme oxygenase (HO1) and that CO is sensed by M. tuberculosis to initiate a dormancy program. Further, mice deficient in HO1 succumb to M. tuberculosis infection more readily than do wild-type mice. Although mouse macrophages control intracellular M. tuberculosis infection through several mechanisms, such as NO synthase, the respiratory burst, acidification, and autophagy, how human macrophages control M. tuberculosis infection remains less well understood. In this article, we show that M. tuberculosis induces and colocalizes with HO1 in both mouse and human tuberculosis lesions in vivo, and that M. tuberculosis induces and colocalizes with HO1 during primary human macrophage infection in vitro. Surprisingly, we find that chemical inhibition of HO1 both reduces inflammatory cytokine production by human macrophages and restricts intracellular growth of mycobacteria. Thus, induction of HO1 by M. tuberculosis infection may be a mycobacterial virulence mechanism to enhance inflammation and bacterial growth. PMID- 27183575 TI - Preferential Use of Public TCR during Autoimmune Encephalomyelitis. AB - How the TCR repertoire, in concert with risk-associated MHC, imposes susceptibility for autoimmune diseases is incompletely resolved. Due largely to recombinatorial biases, a small fraction of TCRalpha or beta-chains are shared by most individuals, or public. If public TCR chains modulate a TCRalphabeta heterodimer's likelihood of productively engaging autoantigen, because they are pervasive and often high frequency, they could also broadly influence disease risk and progression. Prior data, using low-resolution techniques, have identified the heavy use of select public TCR in some autoimmune models. In this study, we assess public repertoire representation in mice with experimental autoimmune encephalomyelitis at high resolution. Saturation sequencing was used to identify >18 * 10(6) TCRbeta sequences from the CNSs, periphery, and thymi of mice at different stages of autoimmune encephalomyelitis and healthy controls. Analyses indicated the prominent representation of a highly diverse public TCRbeta repertoire in the disease response. Preferential formation of public TCR implicated in autoimmunity was identified in preselection thymocytes, and, consistently, public, disease-associated TCRbeta were observed to be commonly oligoclonal. Increased TCR sharing and a focusing of the public TCR response was seen with disease progression. Critically, comparisons of peripheral and CNS repertoires and repertoires from preimmune and diseased mice demonstrated that public TCR were preferentially deployed relative to nonshared, or private, sequences. Our findings implicate public TCR in skewing repertoire response during autoimmunity and suggest that subsets of public TCR sequences may serve as disease-specific biomarkers or influence disease susceptibility or progression. PMID- 27183576 TI - Vitamin A Controls the Presence of RORgamma+ Innate Lymphoid Cells and Lymphoid Tissue in the Small Intestine. AB - Changes in diet and microbiota have determining effects on the function of the mucosal immune system. For example, the active metabolite of vitamin A, retinoic acid (RA), has been described to maintain homeostasis in the intestine by its influence on both lymphocytes and myeloid cells. Additionally, innate lymphoid cells (ILCs), important producers of cytokines necessary for intestinal homeostasis, are also influenced by vitamin A in the small intestines. In this study, we show a reduction of both NCR(-) and NCR(+) ILC3 subsets in the small intestine of mice raised on a vitamin A-deficient diet. Additionally, the percentages of IL-22-producing ILCs were reduced in the absence of dietary vitamin A. Conversely, mice receiving additional RA had a specific increase in the NCR(-) ILC3 subset, which contains the lymphoid tissue inducer cells. The dependence of lymphoid tissue inducer cells on vitamin A was furthermore illustrated by impaired development of enteric lymphoid tissues in vitamin A deficient mice. These effects were a direct consequence of ILC-intrinsic RA signaling, because retinoic acid-related orphan receptor gammat-Cre * RARalpha-DN mice had reduced numbers of NCR(-) and NCR(+) ILC3 subsets within the small intestine. However, lymphoid tissue inducer cells were not affected in these mice nor was the formation of enteric lymphoid tissue, demonstrating that the onset of RA signaling might take place before retinoic acid-related orphan receptor gammat is expressed on lymphoid tissue inducer cells. Taken together, our data show an important role for vitamin A in controlling innate lymphoid cells and, consequently, postnatal formed lymphoid tissues within the small intestines. PMID- 27183574 TI - IL-3 Decreases Cartilage Degeneration by Downregulating Matrix Metalloproteinases and Reduces Joint Destruction in Osteoarthritic Mice. AB - Osteoarthritis (OA) is a chronic disease of articular joints that leads to degeneration of both cartilage and subchondral bone. These degenerative changes are further aggravated by proinflammatory cytokines including IL-1beta and TNF alpha. Previously, we have reported that IL-3, a cytokine secreted by activated T cells, protects cartilage and bone damage in murine models of inflammatory and rheumatoid arthritis. However, how IL-3 protects cartilage degeneration is not yet known. In this study, we investigated the role of IL-3 on cartilage degeneration under both in vitro and in vivo conditions. We found that both mouse and human chondrocytes show strong expression of IL-3R at gene and protein levels. IL-3 increases the expression of mouse chondrocyte-specific genes, Sox9 and collagen type IIa, which were downregulated by IL-1beta. Moreover, IL-3 downregulated IL-1beta- and TNF-alpha-induced expression of matrix metalloproteinases in both mouse and human chondrocytes. Interestingly, IL-3 reduces the degeneration of articular cartilage and subchondral bone microarchitecture in a mouse model of human OA. Moreover, IL-3 showed the preventive and therapeutic effects on cartilage degeneration induced by IL-1beta in micromass pellet cultures of human mesenchymal stem cells. Thus, to our knowledge, we provide the first evidence that IL-3 has therapeutic potential in amelioration of degeneration of articular cartilage and subchondral bone microarchitecture associated with OA. PMID- 27183577 TI - Hyperoxic Exposure of Immature Mice Increases the Inflammatory Response to Subsequent Rhinovirus Infection: Association with Danger Signals. AB - Infants with a history of prematurity and bronchopulmonary dysplasia have a high risk of asthma and viral-induced exacerbations later in life. We hypothesized that hyperoxic exposure, a predisposing factor to bronchopulmonary dysplasia, modulates the innate immune response, producing an exaggerated proinflammatory reaction to viral infection. Two- to 3-d-old C57BL/6J mice were exposed to air or 75% oxygen for 14 d. Mice were infected intranasally with rhinovirus (RV) immediately after O2 exposure. Lung mRNA and protein expression, histology, dendritic cells (DCs), and airway responsiveness were assessed 1-12 d postinfection. Tracheal aspirates from premature human infants were collected for mRNA detection. Hyperoxia increased lung IL-12 expression, which persisted up to 12 d postexposure. Hyperoxia-exposed RV-infected mice showed further increases in IL-12 and increased expression of IFN-gamma, TNF-alpha, CCL2, CCL3, and CCL4, as well as increased airway inflammation and responsiveness. In RV-infected, air exposed mice, the response was not significant. Induced IL-12 expression in hyperoxia-exposed, RV-infected mice was associated with increased IL-12-producing CD103(+) lung DCs. Hyperoxia also increased expression of Clec9a, a CD103(+) DC specific damaged cell-recognition molecule. Hyperoxia increased levels of ATP metabolites and expression of adenosine receptor A1, further evidence of cell damage and related signaling. In human preterm infants, tracheal aspirate Clec9a expression positively correlated with the level of prematurity. Hyperoxic exposure increases the activation of CD103(+), Clec9a(+) DCs, leading to increased inflammation and airway hyperresponsiveness upon RV infection. In premature infants, danger signal-induced DC activation may promote proinflammatory airway responses, thereby increasing respiratory morbidity. PMID- 27183566 TI - Mechanism and Regulation of Protein Synthesis in Saccharomyces cerevisiae. AB - In this review, we provide an overview of protein synthesis in the yeast Saccharomyces cerevisiae The mechanism of protein synthesis is well conserved between yeast and other eukaryotes, and molecular genetic studies in budding yeast have provided critical insights into the fundamental process of translation as well as its regulation. The review focuses on the initiation and elongation phases of protein synthesis with descriptions of the roles of translation initiation and elongation factors that assist the ribosome in binding the messenger RNA (mRNA), selecting the start codon, and synthesizing the polypeptide. We also examine mechanisms of translational control highlighting the mRNA cap-binding proteins and the regulation of GCN4 and CPA1 mRNAs. PMID- 27183579 TI - Novel Insights into the Multiple Sclerosis Risk Gene ANKRD55. AB - An intronic variant in ANKRD55, rs6859219, is a genetic risk factor for multiple sclerosis, but the biological reasons underlying this association are unknown. We characterized the expression of ANKRD55 in human PBMCs and cell lines. Three ANKRD55 transcript variants (Ensembl isoforms 001, 005, and 007) could be detected in PBMCs and CD4(+) T cells but were virtually absent in CD8(+), CD14(+), CD19(+), and CD56(+) cells. Rs6859219 was significantly associated with ANKRD55 transcript levels in PBMCs and CD4(+) T cells and, thus, coincides with a cis-expression quantitative trait locus. The processed noncoding transcript 007 was the most highly expressed variant in CD4(+) T cells, followed by 001 and 005, respectively, but it was not detected in Jurkat, U937, and SH-SY5Y cell lines. Homozygotes for the risk allele produced more than four times more transcript copies than did those for the protective allele. ANKRD55 protein isoforms 005 and 001 were predominantly located in the nucleus of CD4(+) T cells and Jurkat and U937 cells. ANKRD55 was produced by primary cultures of murine hippocampal neurons and microglia, as well as by the murine microglial cell line BV2, and it was induced by inflammatory stimuli. ANKRD55 protein was increased in the murine mouse model of experimental autoimmune encephalomyelitis. Flow cytometric analysis of CNS-infiltrating mononuclear cells showed that CD4(+) T cells and monocytes expressed ANKRD55 in experimental autoimmune encephalomyelitis mice, with the higher fluorescence intensity found in CD4(+) cells. A low percentage of microglia also expressed ANKRD55. Together, these data support an important role for ANKRD55 in multiple sclerosis and neuroinflammation. PMID- 27183578 TI - Hemocyanins Stimulate Innate Immunity by Inducing Different Temporal Patterns of Proinflammatory Cytokine Expression in Macrophages. AB - Hemocyanins induce a potent Th1-dominant immune response with beneficial clinical outcomes when used as a carrier/adjuvant in vaccines and nonspecific immunostimulant in cancer. However, the mechanisms by which hemocyanins trigger innate immune responses, leading to beneficial adaptive immune responses, are unknown. This response is triggered by a proinflammatory signal from various components, of which macrophages are an essential part. To understand how these proteins influence macrophage response, we investigated the effects of mollusks hemocyanins with varying structural and immunological properties, including hemocyanins from Concholepas concholepas, Fissurella latimarginata, and Megathura crenulata (keyhole limpet hemocyanin), on cultures of peritoneal macrophages. Hemocyanins were phagocytosed and slowly processed. Analysis of this process showed differential gene expression along with protein levels of proinflammatory markers, including IL-1beta, IL-6, IL-12p40, and TNF-alpha. An extended expression analysis of 84 cytokines during a 24-h period showed a robust proinflammatory response for F. latimarginata hemocyanin in comparison with keyhole limpet hemocyanin and C. concholepas hemocyanin, which was characterized by an increase in the transcript levels of M1 cytokines involved in leukocyte recruitment. These cytokine genes included chemokines (Cxcl1, Cxcl3, Cxcl5, Ccl2, and Ccl3), ILs (Il1b and Ifng), growth factors (Csf2 and Csf3), and TNF family members (Cd40lg). The protein levels of certain cytokines were increased. However, every hemocyanin maintains downregulated key M2 cytokine genes, including Il4 and Il5 Collectively, our data demonstrate that hemocyanins are able to trigger the release of proinflammatory factors with different patterns of cytokine expression, suggesting differential signaling pathways and transcriptional network mechanisms that lead to the activation of M1-polarized macrophages. PMID- 27183580 TI - Piperlongumine Suppresses Dendritic Cell Maturation by Reducing Production of Reactive Oxygen Species and Has Therapeutic Potential for Rheumatoid Arthritis. AB - Piperlongumine (PLM) is a natural product from the plant Piper longum that inhibits platelet aggregation, atherosclerosis plaque formation, and tumor cell growth. It has potential value in immunomodulation and the management of autoimmune diseases. In this study, we investigated the role of PLM in regulating the differentiation and maturation of dendritic cells (DCs), a critical regulator of immune tolerance, and evaluated its clinical effects in a rheumatoid arthritis mouse model. We found that PLM treatment reduced LPS-induced murine bone marrow derived DC maturation, characterized by reduced expression of CD80/86, secretion of MCP-1, IL-12p70, IL-6, TNFalpha, IFN-gamma, and IL-23, and reduced alloproliferation of T cells; however, PLM does not affect cell differentiation. Furthermore, PLM reduced intracellular reactive oxygen species (ROS) production by DCs and inhibited the activation of p38, JNK, NF-kappaB, and PI3K/Akt signaling pathways. Conversely, PLM increased the expression of GSTP1 and carbonyl reductase 1, two enzymes that counteract ROS effects. ROS inhibition by exogenous N-acetyl-l-cysteine suppressed DC maturation. PLM treatment improved the severity of arthritis and reduced in vivo splenic DC maturation, collagen specific CD4(+) T cell responses, and ROS production in mice with collagen induced arthritis. Taken together, these results suggest that PLM inhibits DC maturation by reducing intracellular ROS production and has potential as a therapeutic agent for rheumatoid arthritis. PMID- 27183581 TI - Autocrine and Paracrine Regulation of Keratinocyte Proliferation through a Novel Nrf2-IL-36gamma Pathway. AB - The Nrf2 transcription factor is well known for its cytoprotective functions through regulation of genes involved in the detoxification of reactive oxygen species or toxic compounds. Therefore, activation of Nrf2 is a promising strategy for the protection of tissues from various types of insults and for cancer prevention. However, recent studies revealed a proinflammatory activity of activated Nrf2 and a stimulating effect on epithelial cell proliferation, but the underlying mechanisms of action and the responsible target genes are largely unknown. Using a combination of gene expression profiling, chromatin immunoprecipitation, and targeted proteomics via selected reaction monitoring, we show that the gene encoding the proinflammatory cytokine IL-36gamma is a novel direct target of Nrf2 in keratinocytes and hepatocytes in vitro and in vivo. As a consequence, upregulation of IL-36gamma expression occurred upon genetic or pharmacological activation of Nrf2 in the epidermis and in the normal and regenerating liver. Functional in vitro studies demonstrate that IL-36gamma directly stimulates proliferation of keratinocytes. In particular, it induces expression of keratinocyte mitogens in fibroblasts, suggesting that the Nrf2-IL 36gamma axis promotes keratinocyte proliferation through a double paracrine loop. These results provide mechanistic insight into Nrf2 action in the control of inflammation and cell proliferation through regulation of a proinflammatory cytokine with a key function in various inflammatory diseases. PMID- 27183582 TI - Cutting Edge: EZH2 Promotes Osteoclastogenesis by Epigenetic Silencing of the Negative Regulator IRF8. AB - Osteoclasts are resorptive cells that are important for homeostatic bone remodeling and pathological bone resorption. Emerging evidence suggests an important role for epigenetic mechanisms in osteoclastogenesis. A recent study showed that epigenetic silencing of the negative regulator of osteoclastogenesis Irf8 by DNA methylation is required for osteoclast differentiation. In this study, we investigated the role of EZH2, which epigenetically silences gene expression by histone methylation, in osteoclastogenesis. Inhibition of EZH2 by the small molecule GSK126, or decreasing its expression using antisense oligonucleotides, impeded osteoclast differentiation. Mechanistically, EZH2 was recruited to the IRF8 promoter after RANKL stimulation to deposit the negative histone mark H3K27me3 and downregulate IRF8 expression. GSK126 attenuated bone loss in the ovariectomy mouse model of postmenopausal osteoporosis. Our findings provide evidence for an additional mechanism of epigenetic IRF8 silencing during osteoclastogenesis that likely works cooperatively with DNA methylation, further emphasizing the importance of IRF8 as a negative regulator of osteoclastogenesis. PMID- 27183583 TI - Homeostatic PPARalpha Signaling Limits Inflammatory Responses to Commensal Microbiota in the Intestine. AB - Dietary lipids and their metabolites activate members of the peroxisome proliferative-activated receptor (PPAR) family of transcription factors and are critical for colonic health. The PPARalpha isoform plays a vital role in regulating inflammation in various disease settings, but its role in intestinal inflammation, commensal homeostasis, and mucosal immunity in the gut are unclear. In this study, we demonstrate that the PPARalpha pathway in innate immune cells orchestrates gut mucosal immunity and commensal homeostasis by regulating the expression of IL-22 and the antimicrobial peptides RegIIIbeta, RegIIIgamma, and calprotectin. Additionally, the PPARalpha pathway is critical for imparting regulatory phenotype in intestinal macrophages. PPARalpha deficiency in mice led to commensal dysbiosis in the gut, resulting in a microbiota-dependent increase in the expression of inflammatory cytokines and enhanced susceptibility to intestinal inflammation. Pharmacological activation of this pathway decreased the expression of inflammatory cytokines and ameliorated colonic inflammation. Taken together, these findings identify a new important innate immune function for the PPARalpha signaling pathway in regulating intestinal inflammation, mucosal immunity, and commensal homeostasis. Thus, the manipulation of the PPARalpha pathway could provide novel opportunities for enhancing mucosal immunity and treating intestinal inflammation. PMID- 27183585 TI - Impaired P2X1 Receptor-Mediated Adhesion in Eosinophils from Asthmatic Patients. AB - Eosinophils play an important role in the pathogenesis of asthma and can be activated by extracellular nucleotides released following cell damage or inflammation. For example, increased ATP concentrations were reported in bronchoalveolar lavage fluids of asthmatic patients. Although eosinophils are known to express several subtypes of P2 receptors for extracellular nucleotides, their function and contribution to asthma remain unclear. In this article, we show that transcripts for P2X1, P2X4, and P2X5 receptors were expressed in healthy and asthmatic eosinophils. The P2X receptor agonist alpha,beta-methylene ATP (alpha,beta-meATP; 10 MUM) evoked rapidly activating and desensitizing inward currents (peak 18 +/- 3 pA/pF at -60 mV) in healthy eosinophils, typical of P2X1 homomeric receptors, which were abolished by the selective P2X1 antagonist NF449 (1 MUM) (3 +/- 2 pA/pF). alpha,beta-meATP-evoked currents were smaller in eosinophils from asthmatic patients (8 +/- 2 versus 27 +/- 5 pA/pF for healthy) but were enhanced following treatment with a high concentration of the nucleotidase apyrase (17 +/- 5 pA/pF for 10 IU/ml and 11 +/- 3 pA/pF for 0.32 IU/ml), indicating that the channels are partially desensitized by extracellular nucleotides. alpha,beta-meATP (10 MUM) increased the expression of CD11b activated form in eosinophils from healthy, but not asthmatic, donors (143 +/- 21% and 108 +/- 11% of control response, respectively). Furthermore, alpha,beta meATP increased healthy (18 +/- 2% compared with control 10 +/- 1%) but not asthmatic (13 +/- 1% versus 10 +/- 0% for control) eosinophil adhesion. Healthy human eosinophils express functional P2X1 receptors whose activation leads to eosinophil alphaMbeta2 integrin-dependent adhesion. P2X1 responses are constitutively reduced in asthmatic compared with healthy eosinophils, probably as the result of an increase in extracellular nucleotide concentration. PMID- 27183584 TI - Decreased SAP Expression in T Cells from Patients with Systemic Lupus Erythematosus Contributes to Early Signaling Abnormalities and Reduced IL-2 Production. AB - T cells from patients with systemic lupus erythematosus (SLE) display a number of abnormalities, including increased early signaling events following engagement of the TCR. Signaling lymphocytic activation molecule family cell surface receptors and the X-chromosome-defined signaling lymphocytic activation molecule-associated protein (SAP) adaptor are important in the development of several immunocyte lineages and modulating the immune response. We present evidence that SAP protein levels are decreased in T cells and in their main subsets isolated from 32 women and three men with SLE, independent of disease activity. In SLE T cells, SAP protein is also subject to increased degradation by caspase-3. Forced expression of SAP in SLE T cells normalized IL-2 production, calcium (Ca(2+)) responses, and tyrosine phosphorylation of a number of proteins. Exposure of normal T cells to SLE serum IgG, known to contain anti-CD3/TCR Abs, resulted in SAP downregulation. We conclude that SLE T cells display reduced levels of the adaptor protein SAP, probably as a result of continuous T cell activation and degradation by caspase 3. Restoration of SAP levels in SLE T cells corrects the overexcitable lupus T cell phenotype. PMID- 27183587 TI - Intracellular RIG-I Signaling Regulates TLR4-Independent Endothelial Inflammatory Responses to Endotoxin. AB - Sepsis is a systemic inflammatory response to infections associated with organ failure that is the most frequent cause of death in hospitalized patients. Exaggerated endothelial activation, altered blood flow, vascular leakage, and other disturbances synergistically contribute to sepsis-induced organ failure. The underlying signaling events associated with endothelial proinflammatory activation are not well understood, yet they likely consist of molecular pathways that act in an endothelium-specific manner. We found that LPS, a critical factor in the pathogenesis of sepsis, is internalized by endothelial cells, leading to intracellular signaling without the need for priming as found recently in immune cells. By identifying a novel role for retinoic acid-inducible gene-I (RIG-I) as a central regulator of endothelial activation functioning independent of TLR4, we provide evidence that the current paradigm of TLR4 solely being responsible for LPS-mediated endothelial responses is incomplete. RIG-I, as well as the adaptor protein mitochondrial antiviral signaling protein, regulates NF-kappaB-mediated induction of adhesion molecules and proinflammatory cytokine expression in response to LPS. Our findings provide essential new insights into the proinflammatory signaling pathways in endothelial cells and suggest that combined endothelial-specific inhibition of RIG-I and TLR4 will provide protection from aberrant endothelial responses associated with sepsis. PMID- 27183586 TI - NKAP Regulates Invariant NKT Cell Proliferation and Differentiation into ROR gammat-Expressing NKT17 Cells. AB - Invariant NKT (iNKT) cells are a unique lineage with characteristics of both adaptive and innate lymphocytes, and they recognize glycolipids presented by an MHC class I-like CD1d molecule. During thymic development, iNKT cells also differentiate into NKT1, NKT2, and NKT17 functional subsets that preferentially produce cytokines IFN-gamma, IL-4, and IL-17, respectively, upon activation. Newly selected iNKT cells undergo a burst of proliferation, which is defective in mice with a specific deletion of NKAP in the iNKT cell lineage, leading to severe reductions in thymic and peripheral iNKT cell numbers. The decreased cell number is not due to defective homeostasis or increased apoptosis, and it is not rescued by Bcl-xL overexpression. NKAP is also required for differentiation into NKT17 cells, but NKT1 and NKT2 cell development and function are unaffected. This failure in NKT17 development is rescued by transgenic expression of promyelocytic leukemia zinc finger; however, the promyelocytic leukemia zinc finger transgene does not restore iNKT cell numbers or the block in positive selection into the iNKT cell lineage in CD4-cre NKAP conditional knockout mice. Therefore, NKAP regulates multiple steps in iNKT cell development and differentiation. PMID- 27183588 TI - Nod1 Limits Colitis-Associated Tumorigenesis by Regulating IFN-gamma Production. AB - Chronic intestinal inflammation is a major risk factor for the development of colorectal cancer. Nod1, a member of the Nod-like receptor (NLR) family of pattern recognition receptors, is a bacterial sensor that has been previously demonstrated to reduce susceptibility of mice to chemically induced colitis and subsequent tumorigenesis, but the mechanism by which it mediates its protection has not been elucidated. In this study, we show that Nod1 expression in the hematopoietic cell compartment is critical for limiting inflammation-induced intestinal tumorigenesis. Specifically, Nod1-deficient T cells exhibit impaired IFN-gamma production during dextran sulfate sodium (DSS)-induced acute inflammation in vivo, and administration of the Nod1 ligand KF1B enhances IFN gamma responses by anti-CD3-activated T cells in vitro. Absence of IFN-gamma signaling results in increased inflammation-associated tumors in mice, and adoptive transfer of Nod1(-/-) or IFNgamma(-/-) T cells into T cell-deficient mice results in increased tumorigenesis as compared with T cell-deficient mice that were adoptively transferred with wild-type T cells. Collectively, these results suggest a previously unappreciated role for the innate immune receptor Nod1 in suppressing colitis-associated tumorigenesis through a T cell-mediated mechanism. PMID- 27183589 TI - Protein Tyrosine Kinase Fyn Regulates TLR4-Elicited Responses on Mast Cells Controlling the Function of a PP2A-PKCalpha/beta Signaling Node Leading to TNF Secretion. AB - Mast cells produce proinflammatory cytokines in response to TLR4 ligands, but the signaling pathways involved are not fully described. In this study, the participation of the Src family kinase Fyn in the production of TNF after stimulation with LPS was evaluated using bone marrow-derived mast cells from wild type and Fyn-deficient mice. Fyn(-/-) cells showed higher LPS-induced secretion of preformed and de novo-synthesized TNF. In both cell types, TNF colocalized with vesicle-associated membrane protein (VAMP)3-positive compartments. Addition of LPS provoked coalescence of VAMP3 and its interaction with synaptosomal associated protein 23; those events were increased in the absence of Fyn. Higher TNF mRNA levels were also observed in Fyn-deficient cells as a result of increased transcription and greater mRNA stability after LPS treatment. Fyn(-/-) cells also showed higher LPS-induced activation of TAK-1 and ERK1/2, whereas IkappaB kinase and IkappaB were phosphorylated, even in basal conditions. Increased responsiveness in Fyn(-/-) cells was associated with a lower activity of protein phosphatase 2A (PP2A) and augmented activity of protein kinase C (PKC)alpha/beta, which was dissociated from PP2A and increased its association with the adapter protein neuroblast differentiation-associated protein (AHNAK, desmoyokin). LPS-induced PKCalpha/beta activity was associated with VAMP3 coalescence in WT and Fyn-deficient cells. Reconstitution of MC-deficient Wsh mice with Fyn(-/-) MCs produced greater LPS-dependent production of TNF in the peritoneal cavity. Our data show that Fyn kinase is activated after TLR4 triggering and exerts an important negative control on LPS-dependent TNF production in MCs controlling the inactivation of PP2Ac and activation of PKCalpha/beta necessary for the secretion of TNF by VAMP3(+) carriers. PMID- 27183590 TI - NKG2D-NKG2D Ligand Interaction Inhibits the Outgrowth of Naturally Arising Low Grade B Cell Lymphoma In Vivo. AB - It is now clear that recognition of nascent tumors by the immune system is critical for survival of the host against cancer. During cancer immunoediting, the ability of the tumor to escape immune recognition is important for tumor development. The immune system recognizes tumors via the presence of classical Ags and also by conserved innate mechanisms. One of these mechanisms is the NKG2D receptor that recognizes ligands whose expression is induced by cell transformation. In this study, we show that in NKG2D receptor-deficient mice, increasing numbers of B cells begin to express NKG2D ligands as they age. Their absence in wild-type mice suggests that these cells are normally cleared by NKG2D expressing cells. NKG2D-deficient mice and mice constitutively expressing NKG2D ligands had increased incidence of B cell tumors, confirming that the inability to clear NKG2D ligand-expressing cells was important in tumor suppression and that NKG2D ligand expression is a marker of nascent tumors. Supporting a role for NKG2D ligand expression in controlling the progression of early-stage B cell lymphomas in humans, we found higher expression of a microRNA that inhibits human NKG2D ligand expression in tumor cells from high-grade compared with low-grade follicular lymphoma patients. PMID- 27183591 TI - Identification of Vaccine-Altered Circulating B Cell Phenotypes Using Mass Cytometry and a Two-Step Clustering Analysis. AB - Broadening our understanding of the abundance and phenotype of B cell subsets that are induced or perturbed by exogenous Ags will improve the vaccine evaluation process. Mass cytometry (CyTOF) is being used to increase the number of markers that can be investigated in single cells, and therefore characterize cell phenotype at an unprecedented level. We designed a panel of CyTOF Abs to compare the B cell response in cynomolgus macaques at baseline, and 8 and 28 d after the second homologous immunization with modified vaccinia virus Ankara. The spanning-tree progression analysis of density-normalized events (SPADE) algorithm was used to identify clusters of CD20(+) B cells. Our data revealed the phenotypic complexity and diversity of circulating B cells at steady-state and significant vaccine-induced changes in the proportions of some B cell clusters. All SPADE clusters, including those altered quantitatively by vaccination, were characterized phenotypically and compared using double hierarchical clustering. Vaccine-altered clusters composed of previously described subsets including CD27(hi)CD21(lo) activated memory and CD27(+)CD21(+) resting memory B cells, and subphenotypes with novel patterns of marker coexpression. The expansion, followed by the contraction, of a single memory B cell SPADE cluster was positively correlated with serum anti-vaccine Ab titers. Similar results were generated by a different algorithm, automatic classification of cellular expression by nonlinear stochastic embedding. In conclusion, we present an in-depth characterization of B cell subphenotypes and proportions, before and after vaccination, using a two step clustering analysis of CyTOF data, which is suitable for longitudinal studies and B cell subsets and biomarkers discovery. PMID- 27183594 TI - Characterization of the Antigen Processing Machinery and Endogenous Peptide Presentation of a Bat MHC Class I Molecule. AB - Bats are a major reservoir of emerging and re-emerging infectious diseases, including severe acute respiratory syndrome-like coronaviruses, henipaviruses, and Ebola virus. Although highly pathogenic to their spillover hosts, bats harbor these viruses, and a large number of other viruses, with little or no clinical signs of disease. How bats asymptomatically coexist with these viruses is unknown. In particular, little is known about bat adaptive immunity, and the presence of functional MHC molecules is mostly inferred from recently described genomes. In this study, we used an affinity purification/mass spectrometry approach to demonstrate that a bat MHC class I molecule, Ptal-N*01:01, binds antigenic peptides and associates with peptide-loading complex components. We identified several bat MHC class I-binding partners, including calnexin, calreticulin, protein disulfide isomerase A3, tapasin, TAP1, and TAP2. Additionally, endogenous peptide ligands isolated from Ptal-N*01:01 displayed a relatively broad length distribution and an unusual preference for a C-terminal proline residue. Finally, we demonstrate that this preference for C-terminal proline residues was observed in Hendra virus-derived peptides presented by Ptal N*01:01 on the surface of infected cells. To our knowledge, this is the first study to identify endogenous and viral MHC class I ligands for any bat species and, as such, provides an important avenue for monitoring and development of vaccines against major bat-borne viruses both in the reservoir and spillover hosts. Additionally, it will provide a foundation to understand the role of adaptive immunity in bat antiviral responses. PMID- 27183592 TI - STAT3 Signaling in B Cells Is Critical for Germinal Center Maintenance and Contributes to the Pathogenesis of Murine Models of Lupus. AB - Ab maturation as well as memory B and plasma cell differentiation occur primarily in the germinal centers (GCs). Systemic lupus erythematosus (SLE) may develop as a result of enhanced GC activity. Previous studies have shown that the dysregulated STAT3 pathway is linked to lupus pathogenesis. However, the exact role of STAT3 in regulating SLE disease progression has not been fully understood. In this study, we demonstrated that STAT3 signaling in B cells is essential for GC formation and maintenance as well as Ab response. Increased cell apoptosis and downregulated Bcl-xL and Mcl-1 antiapoptotic gene expression were found in STAT3-deficient GC B cells. The follicular helper T cell response positively correlated with GC B cells and was significantly decreased in immunized B cell STAT3-deficient mice. STAT3 deficiency also led to the defect of plasma cell differentiation. Furthermore, STAT3 deficiency in autoreactive B cells resulted in decreased autoantibody production. Results obtained from B cell STAT3-deficient B6.MRL/lpr mice suggest that STAT3 signaling significantly contributes to SLE pathogenesis by regulation of GC reactivity, autoantibody production, and kidney pathology. Our findings provide new insights into the role of STAT3 signaling in the maintenance of GC formation and GC B cell differentiation and identify STAT3 as a novel target for treatment of SLE. PMID- 27183593 TI - RBP-J-Regulated miR-182 Promotes TNF-alpha-Induced Osteoclastogenesis. AB - Increased osteoclastogenesis is responsible for osteolysis, which is a severe consequence of inflammatory diseases associated with bone destruction, such as rheumatoid arthritis and periodontitis. The mechanisms that limit osteoclastogenesis under inflammatory conditions are largely unknown. We previously identified transcription factor RBP-J as a key negative regulator that restrains TNF-alpha-induced osteoclastogenesis and inflammatory bone resorption. In this study, we tested whether RBP-J suppresses inflammatory osteoclastogenesis by regulating the expression of microRNAs (miRNAs) important for this process. Using high-throughput sequencing of miRNAs, we obtained the first, to our knowledge, genome-wide profile of miRNA expression induced by TNF-alpha in mouse bone marrow-derived macrophages/osteoclast precursors during inflammatory osteoclastogenesis. Furthermore, we identified miR-182 as a novel miRNA that promotes inflammatory osteoclastogenesis driven by TNF-alpha and whose expression is suppressed by RBP-J. Downregulation of miR-182 dramatically suppressed the enhanced osteoclastogenesis program induced by TNF-alpha in RBP-J-deficient cells. Complementary loss- and gain-of-function approaches showed that miR-182 is a positive regulator of osteoclastogenic transcription factors NFATc1 and B lymphocyte-induced maturation protein-1. Moreover, we identified that direct miR 182 targets, Foxo3 and Maml1, play important inhibitory roles in TNF-alpha mediated osteoclastogenesis. Thus, RBP-J-regulated miR-182 promotes TNF-alpha induced osteoclastogenesis via inhibition of Foxo3 and Maml1. Suppression of miR 182 by RBP-J serves as an important mechanism that restrains TNF-alpha-induced osteoclastogenesis. Our results provide a novel miRNA-mediated mechanism by which RBP-J inhibits osteoclastogenesis and suggest that targeting of the newly described RBP-J-miR-182-Foxo3/Maml1 axis may represent an effective therapeutic approach to suppress inflammatory osteoclastogenesis and bone resorption. PMID- 27183595 TI - The CD4 and CD3deltaepsilon Cytosolic Juxtamembrane Regions Are Proximal within a Compact TCR-CD3-pMHC-CD4 Macrocomplex. AB - TCRs relay information about peptides embedded within MHC molecules (pMHC) to the ITAMs of the associated CD3gammaepsilon, CD3deltaepsilon, and CD3zetazeta signaling modules. CD4 then recruits the Src kinase p56(Lck) (Lck) to the TCR-CD3 complex to phosphorylate the ITAMs, initiate intracellular signaling, and drive CD4(+) T cell fate decisions. Whereas the six ITAMs of CD3zetazeta are key determinants of T cell development, activation, and the execution of effector functions, multiple models predict that CD4 recruits Lck proximal to the four ITAMs of the CD3 heterodimers. We tested these models by placing FRET probes at the cytosolic juxtamembrane regions of CD4 and the CD3 subunits to evaluate their relationship upon pMHC engagement in mouse cell lines. The data are consistent with a compact assembly in which CD4 is proximal to CD3deltaepsilon, CD3zetazeta resides behind the TCR, and CD3gammaepsilon is offset from CD3deltaepsilon. These results advance our understanding of the architecture of the TCR-CD3-pMHC-CD4 macrocomplex and point to regions of high CD4-Lck + ITAM concentrations therein. The findings thus have implications for TCR signaling, as phosphorylation of the CD3 ITAMs by CD4-associated Lck is important for CD4(+) T cell fate decisions. PMID- 27183596 TI - Andrographolide Restores Steroid Sensitivity To Block Lipopolysaccharide/IFN gamma-Induced IL-27 and Airway Hyperresponsiveness in Mice. AB - LPS and IFN-gamma alone or in combination have been implicated in the development of steroid resistance. Combined LPS/IFN-gamma strongly upregulates IL-27 production, which has been linked to steroid-resistant airway hyperresponsiveness (AHR). Andrographolide, a bioactive molecule isolated from the plant Andrographis paniculata, has demonstrated anti-inflammatory and antioxidant properties. The present study investigated whether andrographolide could restore steroid sensitivity to block LPS/IFN-gamma-induced IL-27 production and AHR via its antioxidative property. The mouse macrophage cell line Raw 264.7, mouse primary lung monocytes/macrophages, and BALB/c mice were treated with LPS/IFN-gamma, in the presence and absence of dexamethasone and/or andrographolide. Levels of IL-27 in vitro and in vivo were examined and mouse AHR was assessed. Dexamethasone alone failed to inhibit LPS/IFN-gamma-induced IL-27 production and AHR in mice. Andrographolide significantly restored the suppressive effect of dexamethasone on LPS/IFN-gamma-induced IL-27 mRNA and protein levels in the macrophage cell line and primary lung monocytes/macrophages, mouse bronchoalveolar lavage fluid and lung tissues, and AHR in mice. LPS/IFN-gamma markedly reduced the nuclear level of histone deacetylase (HDAC)2, an essential epigenetic enzyme that mediates steroid anti-inflammatory action. LPS/IFN-gamma also decreased total HDAC activity but increased the total histone acetyltransferase/HDAC activity ratio in mouse lungs. Andrographolide significantly restored nuclear HDAC2 protein levels and total HDAC activity, and it diminished the total histone acetyltransferase/HDAC activity ratio in mouse lungs exposed to LPS/IFN-gamma, possibly via suppression of PI3K/Akt/HDAC2 phosphorylation, and upregulation of the antioxidant transcription factor NF erythroid-2-related factor 2 level and DNA binding activity. Our data suggest that andrographolide may have therapeutic value in resensitizing steroid action in respiratory disorders such as asthma. PMID- 27183598 TI - Myeloid-Restricted AMPKalpha1 Promotes Host Immunity and Protects against IL 12/23p40-Dependent Lung Injury during Hookworm Infection. AB - How the metabolic demand of parasitism affects immune-mediated resistance is poorly understood. Immunity against parasitic helminths requires M2 cells and IL 13, secreted by CD4(+) Th2 and group 2 innate lymphoid cells (ILC2), but whether certain metabolic enzymes control disease outcome has not been addressed. This study demonstrates that AMP-activated protein kinase (AMPK), a key driver of cellular energy, regulates type 2 immunity and restricts lung injury following hookworm infection. Mice with a selective deficiency in the AMPK catalytic alpha1 subunit in alveolar macrophages and conventional dendritic cells produced less IL 13 and CCL17 and had impaired expansion of ILC2 in damaged lung tissue compared with wild-type controls. Defective type 2 responses were marked by increased intestinal worm burdens, exacerbated lung injury, and increased production of IL 12/23p40, which, when neutralized, restored IL-13 production and improved lung recovery. Taken together, these data indicate that defective AMPK activity in myeloid cells negatively impacts type 2 responses through increased IL-12/23p40 production. These data support an emerging concept that myeloid cells and ILC2 can coordinately regulate tissue damage at mucosal sites through mechanisms dependent on metabolic enzyme function. PMID- 27183597 TI - Alveolar Epithelial Cell-Derived Prostaglandin E2 Serves as a Request Signal for Macrophage Secretion of Suppressor of Cytokine Signaling 3 during Innate Inflammation. AB - Preservation of gas exchange mandates that the pulmonary alveolar surface restrain unnecessarily harmful inflammatory responses to the many challenges to which it is exposed. These responses reflect the cross-talk between alveolar epithelial cells (AECs) and resident alveolar macrophages (AMs). We recently determined that AMs can secrete suppressor of cytokine signaling (SOCS) proteins within microparticles. Uptake of these SOCS-containing vesicles by epithelial cells inhibits cytokine-induced STAT activation. However, the ability of epithelial cells to direct AM release of SOCS-containing vesicles in response to inflammatory insults has not been studied. In this study, we report that SOCS3 protein was elevated in bronchoalveolar lavage fluid of both virus- and bacteria infected mice, as well as in an in vivo LPS model of acute inflammation. In vitro studies revealed that AEC-conditioned medium (AEC-CM) enhanced AM SOCS3 secretion above basal levels. Increased amounts of PGE2 were present in AEC-CM after LPS challenge, and both pharmacologic inhibition of PGE2 synthesis in AECs and neutralization of PGE2 in AEC-CM implicated this prostanoid as the major AEC derived factor mediating enhanced AM SOCS3 secretion. Moreover, pharmacologic blockade of PGE2 synthesis or genetic deletion of a PGE2 synthase similarly attenuated the increase in bronchoalveolar lavage fluid SOCS3 noted in lungs of mice challenged with LPS in vivo. These results demonstrate a novel tunable form of cross-talk in which AECs use PGE2 as a signal to request SOCS3 from AMs to dampen their endogenous inflammatory responses during infection. PMID- 27183600 TI - The Hayflick Limit May Determine the Effective Clonal Diversity of Naive T Cells. AB - Having a large number of sufficiently abundant T cell clones is important for adequate protection against diseases. However, as shown in this paper and elsewhere, between young adulthood and >70 y of age the effective clonal diversity of naive CD4/CD8 T cells found in human blood declines by a factor of >10. (Effective clonal diversity accounts for both the number and the abundance of T cell clones.) The causes of this observation are incompletely understood. A previous study proposed that it might result from the emergence of certain rare, replication-enhancing mutations in T cells. In this paper, we propose an even simpler explanation: that it results from the loss of T cells that have attained replicative senescence (i.e., the Hayflick limit). Stochastic numerical simulations of naive T cell population dynamics, based on experimental parameters, show that the rate of homeostatic T cell proliferation increases after the age of ~60 y because naive T cells collectively approach replicative senescence. This leads to a sharp decline of effective clonal diversity after ~70 y, in agreement with empirical data. A mathematical analysis predicts that, without an increase in the naive T cell proliferation rate, this decline will occur >50 yr later than empirically observed. These results are consistent with a model in which exhaustion of the proliferative capacity of naive T cells causes a sharp decline of their effective clonal diversity and imply that therapeutic potentiation of thymopoiesis might either prevent or reverse this outcome. PMID- 27183599 TI - IL-10-Induced miR-155 Targets SOCS1 To Enhance IgE-Mediated Mast Cell Function. AB - IL-10 is an important regulatory cytokine that modulates a wide range of immune cells. Whereas it is best known for its ability to suppress immune responses, IL 10 has been found to be pathogenic in several human and animal studies of immune mediated diseases. There is a considerable gap in our understanding of the molecular mechanisms behind the stimulatory effects of IL-10 during allergic inflammation. IL-10 treatment has been shown to suppress mast cell TNF production. In this study, we report that whereas TNF secretion was reduced, IL 10 surprisingly enhanced IgE-mediated protease and cytokine production both in vitro and in vivo. This stimulatory effect was consistent in mouse and human skin mast cells. IL-10 enhanced activation of the key FcepsilonRI signaling proteins Stat5, JNK, and ERK. We demonstrate that IL-10 effects are dependent on Stat3 activation, eliciting miR-155 expression, with a resulting loss of suppressor of cytokine signaling-1. The importance of miR-155 was demonstrated by the inability of IL-10 to enhance anaphylaxis in miR-155-deficient mice. Taken together, our results reveal an IL-10-induced, Stat3-miR-155 signaling pathway that can promote mast cell responses. PMID- 27183601 TI - Intravaginal Zinc Oxide Tetrapod Nanoparticles as Novel Immunoprotective Agents against Genital Herpes. AB - Virtually all efforts to generate an effective protection against the life-long, recurrent genital infections caused by HSV-2 have failed. Apart from sexual transmission, the virus can also be transmitted from mothers to neonates, and it is a key facilitator of HIV coacquisition. In this article, we uncover a nanoimmunotherapy using specially designed zinc oxide tetrapod nanoparticles (ZOTEN) with engineered oxygen vacancies. We demonstrate that ZOTEN, when used intravaginally as a microbicide, is an effective suppressor of HSV-2 genital infection in female BALB/c mice. The strong HSV-2 trapping ability of ZOTEN significantly reduced the clinical signs of vaginal infection and effectively decreased animal mortality. In parallel, ZOTEN promoted the presentation of bound HSV-2 virions to mucosal APCs, enhancing T cell-mediated and Ab-mediated responses to the infection, and thereby suppressing a reinfection. We also found that ZOTEN exhibits strong adjuvant-like properties, which is highly comparable with alum, a commonly used adjuvant. Overall, to our knowledge, our study provides the very first evidence for the protective efficacy of an intravaginal microbicide/vaccine or microbivac platform against primary and secondary female genital herpes infections. PMID- 27183602 TI - Dual Function of Ccr5 during Langat Virus Encephalitis: Reduction in Neutrophil Mediated Central Nervous System Inflammation and Increase in T Cell-Mediated Viral Clearance. AB - Tick-borne encephalitis virus (TBEV) is a vector-transmitted flavivirus that causes potentially fatal neurologic infection. There are thousands of cases reported annually, and despite the availability of an effective vaccine, the incidence of TBEV is increasing worldwide. Importantly, up to 30% of affected individuals develop long-term neurologic sequelae. We investigated the role of chemokine receptor Ccr5 in a mouse model of TBEV infection using the naturally attenuated tick-borne flavivirus Langat virus (LGTV). Ccr5-deficient mice presented with an increase in viral replication within the CNS and decreased survival during LGTV encephalitis compared with wild-type controls. This enhanced susceptibility was due to the temporal lag in lymphocyte migration into the CNS. Adoptive transfer of wild-type T cells, but not Ccr5-deficient T cells, significantly improved survival outcome in LGTV-infected Ccr5-deficient mice. Concomitantly, a significant increase in neutrophil migration into the CNS in LGTV-infected Ccr5(-/-) mice was documented at the late stage of infection. Ab mediated depletion of neutrophils in Ccr5(-/-) mice resulted in a significant improvement in mortality, a decrease in viral load, and a decrease in overall tissue damage in the CNS compared with isotype control-treated mice. Ccr5 is crucial in directing T cells toward the LGTV-infected brain, as well as in suppressing neutrophil-mediated inflammation within the CNS. PMID- 27183603 TI - Elastin-Derived Peptides Promote Abdominal Aortic Aneurysm Formation by Modulating M1/M2 Macrophage Polarization. AB - Abdominal aortic aneurysm is a dynamic vascular disease characterized by inflammatory cell invasion and extracellular matrix degradation. Damage to elastin in the extracellular matrix results in release of elastin-derived peptides (EDPs), which are chemotactic for inflammatory cells such as monocytes. Their effect on macrophage polarization is less well known. Proinflammatory M1 macrophages initially are recruited to sites of injury, but, if their effects are prolonged, they can lead to chronic inflammation that prevents normal tissue repair. Conversely, anti-inflammatory M2 macrophages reduce inflammation and aid in wound healing. Thus, a proper M1/M2 ratio is vital for tissue homeostasis. Abdominal aortic aneurysm tissue reveals a high M1/M2 ratio in which proinflammatory cells and their associated markers dominate. In the current study, in vitro treatment of bone marrow-derived macrophages with EDPs induced M1 macrophage polarization. By using C57BL/6 mice, Ab-mediated neutralization of EDPs reduced aortic dilation, matrix metalloproteinase activity, and proinflammatory cytokine expression at early and late time points after aneurysm induction. Furthermore, direct manipulation of the M1/M2 balance altered aortic dilation. Injection of M2-polarized macrophages reduced aortic dilation after aneurysm induction. EDPs promoted a proinflammatory environment in aortic tissue by inducing M1 polarization, and neutralization of EDPs attenuated aortic dilation. The M1/M2 imbalance is vital to aneurysm formation. PMID- 27183604 TI - Highly Dynamic Transcriptional Signature of Distinct Macrophage Subsets during Sterile Inflammation, Resolution, and Tissue Repair. AB - Macrophage gene expression determines phagocyte responses and effector functions. Macrophage plasticity has been mainly addressed in in vitro models that do not account for the environmental complexity observed in vivo. In this study, we show that microarray gene expression profiling revealed a highly dynamic landscape of transcriptomic changes of Ly6C(pos)CX3CR1(lo) and Ly6C(neg)CX3CR1(hi) macrophage populations during skeletal muscle regeneration after a sterile damage. Systematic gene expression analysis revealed that the time elapsed, much more than Ly6C status, was correlated with the largest differential gene expression, indicating that the time course of inflammation was the predominant driving force of macrophage gene expression. Moreover, Ly6C(pos)/Ly6C(neg) subsets could not have been aligned to canonical M1/M2 profiles. Instead, a combination of analyses suggested the existence of four main features of muscle-derived macrophages specifying important steps of regeneration: 1) infiltrating Ly6C(pos) macrophages expressed acute-phase proteins and exhibited an inflammatory profile independent of IFN-gamma, making them damage-associated macrophages; 2) metabolic changes of macrophages, characterized by a decreased glycolysis and an increased tricarboxylic acid cycle/oxidative pathway, preceded the switch to and sustained their anti-inflammatory profile; 3) Ly6C(neg) macrophages, originating from skewed Ly6C(pos) cells, actively proliferated; and 4) later on, restorative Ly6C(neg) macrophages were characterized by a novel profile, indicative of secretion of molecules involved in intercellular communications, notably matrix related molecules. These results show the highly dynamic nature of the macrophage response at the molecular level after an acute tissue injury and subsequent repair, and associate a specific signature of macrophages to predictive specialized functions of macrophages at each step of tissue injury/repair. PMID- 27183606 TI - Thymic Mesenchymal Cells Have a Distinct Transcriptomic Profile. AB - In order to understand the role of mesenchymal cells (MCs) in the adult thymus, we performed whole transcriptome analyses of primary thymic, bone, and skin MCs. These three MC populations shared expression of 2850 core MC genes involved in generic processes including interactions with tissue-resident macrophages. Moreover, we discovered that 2036 genes were differentially expressed, by at least 5-fold, in the three MC populations. Genes preferentially expressed in thymic MCs are instrumental in clearance of apoptotic thymocytes by macrophages, maintenance of a noninflammatory milieu, and attraction-expansion of thymocyte progenitors. Thymic and bone MCs share other sets of differentially expressed genes implicated in resolution of inflammation and expansion of hematolymphoid progenitors. Consistent with the fact that thymic and skin MCs have to support epithelial cells, they express at higher levels genes mediating epithelial cell adhesion to basement membrane and mesenchymal-epithelial cross-talk. Differentially expressed genes preferentially expressed by bone MCs are connected to formation and remodeling of bone, whereas those preferentially expressed in skin MCs are involved in skin and hair follicle homeostasis. We conclude that MCs from different organs display substantial heterogeneity and that the transcriptome of thymic MCs is exquisitely suited for interactions with epithelial and hematolymphoid cells in an environment with a high apoptosis rate. PMID- 27183605 TI - RIPK1 and PGAM5 Control Leishmania Replication through Distinct Mechanisms. AB - Leishmaniasis is an important parasitic disease found in the tropics and subtropics. Cutaneous and visceral leishmaniasis affect an estimated 1.5 million people worldwide. Despite its human health relevance, relatively little is known about the cell death pathways that control Leishmania replication in the host. Necroptosis is a recently identified form of cell death with potent antiviral effects. Receptor interacting protein kinase 1 (RIPK1) is a critical kinase that mediates necroptosis downstream of death receptors and TLRs. Heme, a product of hemoglobin catabolism during certain intracellular pathogen infections, is also a potent inducer of macrophage necroptosis. We found that human visceral leishmaniasis patients exhibit elevated serum levels of heme. Therefore, we examined the impact of heme and necroptosis on Leishmania replication. Indeed, heme potently inhibited Leishmania replication in bone marrow-derived macrophages. Moreover, we found that inhibition of RIPK1 kinase activity also enhanced parasite replication in the absence of heme. We further found that the mitochondrial phosphatase phosphoglycerate mutase family member 5 (PGAM5), a putative downstream effector of RIPK1, was also required for inhibition of Leishmania replication. In mouse infection, both PGAM5 and RIPK1 kinase activity are required for IL-1beta expression in response to Leishmania However, PGAM5, but not RIPK1 kinase activity, was directly responsible for Leishmania-induced IL 1beta secretion and NO production in bone marrow-derived macrophages. Collectively, these results revealed that RIPK1 and PGAM5 function independently to exert optimal control of Leishmania replication in the host. PMID- 27183607 TI - Serum Cytokines as Biomarkers of Early Trypanosoma cruzi infection by Congenital Exposure. AB - Trypanosoma cruzi, the causing agent of Chagas disease, leads to an activation of the immune system in congenitally infected infants. In this study, we measured a set of cytokines/chemokines and the levels of parasitemia by quantitative PCR in the circulation of neonates born to T. cruzi-infected mothers to evaluate the predictive value of these mediators as biomarkers of congenital transmission. We conducted a retrospective cohort study of 35 infants with congenital T. cruzi infection, of which 15 and 10 infants had been diagnosed by detection of parasites by microscopy in the first and sixth month after delivery, respectively, and the remaining 10 had been diagnosed by the presence of T. cruzi specific Abs at 10-12 mo old. Uninfected infants born to either T. cruzi-infected or uninfected mothers were also evaluated as controls. The plasma levels of IL 17A, MCP-1, and monokine induced by IFN-gamma were increased in infants congenitally infected with T. cruzi, even before they developed detectable parasitemia or seroconversion. Infants diagnosed between 6 and 12 mo old also showed increased levels of IL-6 and IL-17F at 1 mo of age. Conversely, infants who did not develop congenital T. cruzi infection had higher levels of IFN-gamma than infected infants born to uninfected mothers. Monokine induced by IFN-gamma, MCP-1, and IFN-gamma production induced in T. cruzi-infected infants correlated with parasitemia, whereas the plasma levels of IL-17A, IL-17F, and IL-6 were less parasite load dependent. These findings support the existence of a distinct profile of cytokines and chemokines in the circulation of infants born to T. cruzi-infected mothers, which might predict congenital infection. PMID- 27183608 TI - TGF-beta Signaling in Dendritic Cells Governs Colonic Homeostasis by Controlling Epithelial Differentiation and the Luminal Microbiota. AB - Dendritic cells (DCs) mediate host immune responses to gut microbes and play critical roles in inflammatory bowel disease. In this study, we examined the role of TGF-beta signaling in DCs in colonic homeostasis. CD11c-cre Tgfbr2(fl/fl) mice developed spontaneous colitis, and CD11c-cre Tgfbr2(fl/+) mice exhibited susceptibility to dextran sulfate sodium-induced colitis. Colitis in these mice was characterized by goblet cell depletion and dysbiosis caused by Enterobacteriaceae enrichment. Wild-type mice gavaged with Enterobacteriaceae from CD11c-cre Tgfbr2(fl/fl) mice feces showed severe colitis after dextran sulfate sodium treatment, whereas those treated with Notch inhibitor exhibited attenuated colonic injury with increased goblet cell numbers, thickened mucus layer, and fewer fecal Enterobacteriaceae Wild-type mice transplanted with CD11c cre Tgfbr2(fl/fl) bone marrow developed colitis showing increased Jagged1 and Jagged2 in DCs, increased Hes1 levels in epithelium, and goblet cell depletion. These findings suggest that TGF-beta signaling in DCs regulates intestinal homeostasis by modulating epithelial cell differentiation and fecal microbiota. PMID- 27183609 TI - Heightened Immune Activation in Fetuses with Gastroschisis May Be Blocked by Targeting IL-5. AB - The development of the fetal immune system during pregnancy is a well orchestrated process with important consequences for fetal and neonatal health, but prenatal factors that affect immune activation are poorly understood. We hypothesized that chronic fetal inflammation may lead to alterations in development of the fetal immune system. To test this hypothesis, we examined neonates with gastroschisis, a congenital abdominal wall defect that leads to exposure of the fetal intestines to amniotic fluid, with resultant intestinal inflammation. We determined that patients with gastroschisis show high systemic levels of inflammatory cytokines and chemokines such as eotaxin, as well as earlier activation of CD4(+) and CD8(+) effector and memory T cells in the cord blood compared with controls. Additionally, increased numbers of T cells and eosinophils infiltrate the serosa and mucosa of the inflamed intestines. Using a mouse model of gastroschisis, we observed higher numbers of eosinophils and both type 2 and type 3 innate lymphoid cells (ILC2 and ILC3), specifically in the portion of organs exposed to the amniotic fluid. Given the role of IL-5 produced by ILC2 in regulating eosinophil development and survival, we determined that maternal or fetal administration of the anti-IL-5 neutralizing Ab, or a depleting Ab against ILCs, can both effectively reduce intestinal eosinophilia. Thus, a congenital anomaly causing chronic inflammation can alter the composition of circulating and tissue-resident fetal immune cells. Given the high rate of prenatal and neonatal complications in these patients, such changes have clinical significance and might become targets for fetal therapy. PMID- 27183610 TI - Cholesterol Crystals Activate the Lectin Complement Pathway via Ficolin-2 and Mannose-Binding Lectin: Implications for the Progression of Atherosclerosis. AB - Cholesterol crystals (CC) play an essential role in the formation of atherosclerotic plaques. CC activate the classical and the alternative complement pathways, but the role of the lectin pathway is unknown. We hypothesized that the pattern recognition molecules (PRMs) from the lectin pathway bind CC and function as an upstream innate inflammatory signal in the pathophysiology of atherosclerosis. We investigated the binding of the PRMs mannose-binding lectin (MBL), ficolin-1, ficolin-2, and ficolin-3, the associated serine proteases, and complement activation products to CC in vitro using recombinant proteins, specific inhibitors, as well as deficient and normal sera. Additionally, we examined the deposition of ficolin-2 and MBL in human carotid plaques by immunohistochemistry and fluorescence microscopy. The results showed that the lectin pathway was activated on CC by binding of ficolin-2 and MBL in vitro, resulting in activation and deposition of complement activation products. MBL bound to CC in a calcium-dependent manner whereas ficolin-2 binding was calcium independent. No binding was observed for ficolin-1 or ficolin-3. MBL and ficolin 2 were present in human carotid plaques, and binding of MBL to CC was confirmed in vivo by immunohistochemistry, showing localization of MBL around CC clefts. Moreover, we demonstrated that IgM, but not IgG, bound to CC in vitro and that C1q binding was facilitated by IgM. In conclusion, our study demonstrates that PRMs from the lectin pathway recognize CC and provides evidence for an important role for this pathway in the inflammatory response induced by CC in the pathophysiology of atherosclerosis. PMID- 27183612 TI - Cutting Edge: Skin CCR10+ CD8+ T Cells Support Resident Regulatory T Cells through the B7.2/Receptor Axis To Regulate Local Immune Homeostasis and Response. AB - Resident T cells in barrier tissues are important in protecting against foreign agents but can also contribute to inflammatory diseases if dysregulated. How T cell homeostasis is maintained in barrier tissues is still poorly understood. We report that resident CD8(+) T cells directly support maintenance of regulatory T cells (Tregs) in the skin to promote immune homeostasis. Impaired establishment of resident CD8(+) T cells caused by knockout of the skin-homing chemokine receptor CCR10 resulted in an altered balance of resident Tregs and CD4(+) effector T cells in the skin and overreactive inflammatory responses to cutaneous stimulations. Furthermore, B7.2 expressed on skin CD8(+) T cells supports the survival of Tregs, likely through interaction with its receptor CTLA-4, which is highly expressed on skin Tregs. Our findings provide novel insights into T cell homeostatic regulation in the skin and may improve our understanding of the pathobiology of tissue inflammatory diseases. PMID- 27183613 TI - Phenotypic and Functional Plasticity of Murine Intestinal NKp46+ Group 3 Innate Lymphoid Cells. AB - Group 3 innate lymphoid cells (ILC3) actively participate in mucosal defense and homeostasis through prompt secretion of IL-17A, IL-22, and IFN-gamma. Reports identify two ILC3 lineages: a CCR6(+)T-bet(-) subset that appears early in embryonic development and promotes lymphoid organogenesis and a CCR6(-)T-bet(+) subset that emerges after microbial colonization and harbors NKp46(+) ILC3. We demonstrate that NKp46 expression in the ILC3 subset is highly unstable. Cell fate mapping using Ncr1(CreGFP) * Rosa26(RFP) mice revealed the existence of an intestinal RFP(+) ILC3 subset (Ncr1(FM)) lacking NKp46 expression at the transcript and protein levels. Ncr1(FM) ILC3 produced more IL-22 and were distinguishable from NKp46(+) ILC3 by differential CD117, CD49a, DNAX accessory molecule-1, and, surprisingly, CCR6 expression. Ncr1(FM) ILC3 emerged after birth and persisted in adult mice following broad-spectrum antibiotic treatment. These results identify an unexpected phenotypic instability within NKp46(+) ILC3 that suggests a major role for environmental signals in tuning ILC3 functional plasticity. PMID- 27183611 TI - Aerosol Delivery of a Candidate Universal Influenza Vaccine Reduces Viral Load in Pigs Challenged with Pandemic H1N1 Virus. AB - Influenza A viruses are a major health threat to livestock and humans, causing considerable mortality, morbidity, and economic loss. Current inactivated influenza vaccines are strain specific and new vaccines need to be produced at frequent intervals to combat newly arising influenza virus strains, so that a universal vaccine is highly desirable. We show that pandemic H1N1 influenza virus in which the hemagglutinin signal sequence has been suppressed (S-FLU), when administered to pigs by aerosol can induce CD4 and CD8 T cell immune responses in blood, bronchoalveolar lavage (BAL), and tracheobronchial lymph nodes. Neutralizing Ab was not produced. Detection of a BAL response correlated with a reduction in viral titer in nasal swabs and lungs, following challenge with H1N1 pandemic virus. Intratracheal immunization with a higher dose of a heterologous H5N1 S-FLU vaccine induced weaker BAL and stronger tracheobronchial lymph node responses and a lesser reduction in viral titer. We conclude that local cellular immune responses are important for protection against influenza A virus infection, that these can be most efficiently induced by aerosol immunization targeting the lower respiratory tract, and that S-FLU is a promising universal influenza vaccine candidate. PMID- 27183614 TI - Regulation of Complement-Dependent Cytotoxicity by MicroRNAs miR-200b, miR-200c, and miR-217. AB - The impact of microRNAs (miRNAs) known to regulate numerous biologic processes on complement-dependent cytotoxicity (CDC) was investigated in K562 cells. The C5b-9 complex is the executioner of CDC. Cells protect themselves from CDC by C5b-9 elimination, a process involving the mitochondrial chaperone mortalin/GRP75. Potential miR-200 (b and c) and miR-217 regulatory sites were identified in mortalin mRNA. Overexpression of miR-200b/c or miR-217 lowered the expression of mortalin mRNA. miRNA inhibitors for miR-200b, miR-200c, or miR-217 enhanced mortalin mRNA level. Unexpectedly, these miRNA modulators had no significant effect on mortalin protein level. Metabolic labeling analysis demonstrated that, to compensate for reduction in mortalin mRNA level, the cells increased the rate of synthesis of mortalin protein. Cells overexpressing miR-200b/c or miR-217 showed reduced sensitivity to CDC, whereas inhibition of miR-200c and miR-217 enhanced cell death. miR-200b/c overexpression reduced C5b-9 binding and enhanced its release from the cells and promoted mortalin relocation to the plasma membrane. Inhibition of miR-200 (b and c) and miR-217 had no effect on the expression level of the membrane complement-regulatory proteins CD46, CD55, and CD59. However, overexpression of miR-200b/c or miR-217 enhanced expression of CD46 and CD55 (not of CD59). Overall, the data demonstrate miRNA regulation of cell sensitivity to CDC. We identified miR-200b, miR-200c, and miR-217 as regulators of mortalin and, perhaps indirectly, of CD46 and CD55. Cell exposure to a sublytic dose of complement was shown to increase expression of miR-200 (b and c), suggesting that complement C5b-9 exerts a feedback-regulatory effect on these miRNAs. PMID- 27183615 TI - Dynamics of Individual T Cell Repertoires: From Cord Blood to Centenarians. AB - The diversity, architecture, and dynamics of the TCR repertoire largely determine our ability to effectively withstand infections and malignancies with minimal mistargeting of immune responses. In this study, we have employed deep TCRbeta repertoire sequencing with normalization based on unique molecular identifiers to explore the long-term dynamics of T cell immunity. We demonstrate remarkable stability of repertoire, where approximately half of all T cells in peripheral blood are represented by clones that persist and generally preserve their frequencies for 3 y. We further characterize the extremes of lifelong TCR repertoire evolution, analyzing samples ranging from umbilical cord blood to centenarian peripheral blood. We show that the fetal TCR repertoire, albeit structurally maintained within regulated borders due to the lower numbers of randomly added nucleotides, is not limited with respect to observed functional diversity. We reveal decreased efficiency of nonsense-mediated mRNA decay in umbilical cord blood, which may reflect specific regulatory mechanisms in development. Furthermore, we demonstrate that human TCR repertoires are functionally more similar at birth but diverge during life, and we track the lifelong behavior of CMV- and EBV-specific T cell clonotypes. Finally, we reveal gender differences in dynamics of TCR diversity constriction, which come to naught in the oldest age. Based on our data, we propose a more general explanation for the previous observations on the relationships between longevity and immunity. PMID- 27183618 TI - Dendritic Cells and Monocytes with Distinct Inflammatory Responses Reside in Lung Mucosa of Healthy Humans. AB - Every breath we take contains potentially harmful pathogens or allergens. Dendritic cells (DCs), monocytes, and macrophages are essential in maintaining a delicate balance of initiating immunity without causing collateral damage to the lungs because of an exaggerated inflammatory response. To document the diversity of lung mononuclear phagocytes at steady-state, we performed bronchoscopies on 20 healthy subjects, sampling the proximal and distal airways (bronchial wash and bronchoalveolar lavage, respectively), as well as mucosal tissue (endobronchial biopsies). In addition to a substantial population of alveolar macrophages, we identified subpopulations of monocytes, myeloid DCs (MDCs), and plasmacytoid DCs in the lung mucosa. Intermediate monocytes and MDCs were highly frequent in the airways compared with peripheral blood. Strikingly, the density of mononuclear phagocytes increased upon descending the airways. Monocytes from blood and airways produced 10-fold more proinflammatory cytokines than MDCs upon ex vivo stimulation. However, airway monocytes were less inflammatory than blood monocytes, suggesting a more tolerant nature. The findings of this study establish how to identify human lung mononuclear phagocytes and how they function in normal conditions, so that dysregulations in patients with respiratory diseases can be detected to elucidate their contribution to immunity or pathogenesis. PMID- 27183617 TI - IL-10 Enhances IgE-Mediated Mast Cell Responses and Is Essential for the Development of Experimental Food Allergy in IL-10-Deficient Mice. AB - IL-10 is a key pleiotropic cytokine that can both promote and curb Th2-dependent allergic responses. In this study, we demonstrate a novel role for IL-10 in promoting mast cell expansion and the development of IgE-mediated food allergy. Oral OVA challenge in sensitized BALB/c mice resulted in a robust intestinal mast cell response accompanied by allergic diarrhea, mast cell activation, and a predominance of Th2 cytokines, including enhanced IL-10 expression. In contrast, the development of intestinal anaphylaxis, including diarrhea, mast cell activation, and Th2 cytokine production, was significantly attenuated in IL-10(-/ ) mice compared with wild-type (WT) controls. IL-10 also directly promoted the expansion, survival, and activation of mast cells; increased FcepsilonRI expression on mast cells; and enhanced the production of mast cell cytokines. IL 10(-/-) mast cells had reduced functional capacity, which could be restored by exogenous IL-10. Similarly, attenuated passive anaphylaxis in IL-10(-/-) mice could be restored by IL-10 administration. The adoptive transfer of WT mast cells restored allergic symptoms in IL-10(-/-) mice, suggesting that the attenuated phenotype observed in these animals is due to a deficiency in IL-10-responding mast cells. Lastly, transfer of WT CD4 T cells also restored allergic diarrhea and intestinal mast cell numbers in IL-10(-/-) mice, suggesting that the regulation of IL-10-mediated intestinal mast cell expansion is T cell dependent. Our observations demonstrate a critical role for IL-10 in driving mucosal mast cell expansion and activation, suggesting that, in its absence, mast cell function is impaired, leading to attenuated food allergy symptoms. PMID- 27183619 TI - Distinct Mechanisms Underlie Boosted Polysaccharide-Specific IgG Responses Following Secondary Challenge with Intact Gram-Negative versus Gram-Positive Extracellular Bacteria. AB - Priming of mice with intact, heat-killed cells of Gram-negative Neisseria meningitidis, capsular serogroup C (MenC) or Gram-positive group B Streptococcus, capsular type III (GBS-III) bacteria resulted in augmented serum polysaccharide (PS)-specific IgG titers following booster immunization. Induction of memory required CD4(+) T cells during primary immunization. We determined whether PS specific memory for IgG production was contained within the B cell and/or T cell populations, and whether augmented IgG responses following booster immunization were also dependent on CD4(+) T cells. Adoptive transfer of purified B cells from MenC- or GBS-III-primed, but not naive mice resulted in augmented PS-specific IgG responses following booster immunization. Similar responses were observed when cotransferred CD4(+) T cells were from primed or naive mice. Similarly, primary immunization with unencapsulated MenC or GBS-III, to potentially prime CD4(+) T cells, failed to enhance PS-specific IgG responses following booster immunization with their encapsulated isogenic partners. Furthermore, in contrast to GBS-III, depletion of CD4(+) T cells during secondary immunization with MenC or another Gram-negative bacteria, Acinetobacter baumannii, did not inhibit augmented PS specific IgG booster responses of mice primed with heat-killed cells. Also, in contrast with GBS-III, booster immunization of MenC-primed mice with isolated MenC-PS, a TI Ag, or a conjugate of MenC-PS and tetanus toxoid elicited an augmented PS-specific IgG response similar to booster immunization with intact MenC. These data demonstrate that memory for augmented PS-specific IgG booster responses to Gram-negative and Gram-positive bacteria is contained solely within the B cell compartment, with a differential requirement for CD4(+) T cells for augmented IgG responses following booster immunization. PMID- 27183616 TI - Properdin-Mediated C5a Production Enhances Stable Binding of Platelets to Granulocytes in Human Whole Blood. AB - Enhanced levels of platelet/granulocyte aggregates (PGAs) are found in patients suffering from many different inflammatory vascular diseases, and their formation in animal models of vascular disease is associated with increased thromboinflammation and worsened outcomes. The complement system, a part of the innate immune system, influences PGA formation, but the mechanisms for its effects are unknown. In this study, we have defined complement-mediated mechanisms that enhance PGA formation in human whole blood stimulated with thrombin receptor-activating peptide (TRAP) using ex vivo flow cytometry assays. We demonstrate that physiological properdin, a positive regulator of complement alternative pathway activity, increases PGA formation when added to TRAP stimulated blood. All physiological properdin forms increase PGA formation, but properdin tetramers are the most efficient at increasing complement activity and PGA formation. Inhibition of endogenous properdin, either circulating in the blood or produced locally by leukocytes, impairs TRAP-mediated PGA formation to the same level as specific inhibition of either the alternative or classical pathway. Additionally, blocking the interaction of C5a with its cellular receptor prevents properdin-mediated increases in PGA formation. Adding either properdin tetramers or C5a to whole blood increases CD11b expression on granulocytes, and this increase is prevented by blockade of the C5a-C5a receptor axis. Finally, we demonstrate that the effects of properdin on PGA formation are tightly regulated by Factor H. Cumulatively, our data indicate that properdin enhances PGA formation via increased production of C5a, and that inhibition of properdin function has therapeutic potential to limit thromboinflammation in diseases characterized by increased PGA formation. PMID- 27183620 TI - Privileged Antigen Presentation in Splenic B Cell Follicles Maximizes T Cell Responses in Prime-Boost Vaccination. AB - Effector T cells (TEFF) are a barrier to booster vaccination because they can rapidly kill Ag-bearing APCs before memory T cells are engaged. We report in this study that i.v. delivery of rhabdoviral vectors leads to direct infection of follicular B cells in the spleen, where the earliest evidence of secondary T cell responses was observed. This allows booster immunizations to rapidly expand CD8(+) central memory T cells (TCM) during the acute phase of the primary response that is dominated by TEFF Interestingly, although the ablation of B cells before boosting with rhabdoviral vectors diminishes the expansion of memory T cells, B cells do not present Ags directly. Instead, depletion of CD11c(+) dendritic cells abrogates secondary T cell expansion, suggesting that virus infected follicular B cells may function as an Ag source for local DCs to subsequently capture and present the Ag. Because TCM are located within B cell follicles in the spleen whereas TEFF cannot traffic through follicular regions, Ag production and presentation by follicular APCs represent a unique mechanism to secure engagement of TCM during an ongoing effector response. Our data offer insights into novel strategies for rapid expansion of CD8(+) T cells using prime boost vaccines by targeting privileged sites for Ag presentation. PMID- 27183622 TI - Heterologous Vaccination and Checkpoint Blockade Synergize To Induce Antileukemia Immunity. AB - Checkpoint blockade-based immunotherapies are effective in cancers with high numbers of nonsynonymous mutations. In contrast, current paradigms suggest that such approaches will be ineffective in cancers with few nonsynonymous mutations. To examine this issue, we made use of a murine model of BCR-ABL(+) B-lineage acute lymphoblastic leukemia. Using a principal component analysis, we found that robust MHC class II expression, coupled with appropriate costimulation, correlated with lower leukemic burden. We next assessed whether checkpoint blockade or therapeutic vaccination could improve survival in mice with pre established leukemia. Consistent with the low mutation load in our leukemia model, we found that checkpoint blockade alone had only modest effects on survival. In contrast, robust heterologous vaccination with a peptide derived from the BCR-ABL fusion (BAp), a key driver mutation, generated a small population of mice that survived long-term. Checkpoint blockade strongly synergized with heterologous vaccination to enhance overall survival in mice with leukemia. Enhanced survival did not correlate with numbers of BAp:I-A(b)-specific T cells, but rather with increased expression of IL-10, IL-17, and granzyme B and decreased expression of programmed death 1 on these cells. Our findings demonstrate that vaccination to key driver mutations cooperates with checkpoint blockade and allows for immune control of cancers with low nonsynonymous mutation loads. PMID- 27183621 TI - TNF and CD28 Signaling Play Unique but Complementary Roles in the Systemic Recruitment of Innate Immune Cells after Staphylococcus aureus Enterotoxin A Inhalation. AB - Staphylococcus aureus enterotoxins cause debilitating systemic inflammatory responses, but how they spread systemically and trigger inflammatory cascade is unclear. In this study, we showed in mice that after inhalation, Staphylococcus aureus enterotoxin A rapidly entered the bloodstream and induced T cells to orchestrate systemic recruitment of inflammatory monocytes and neutrophils. To study the mechanism used by specific T cells that mediate this process, a systems approach revealed inducible and noninducible pathways as potential targets. It was found that TNF caused neutrophil entry into the peripheral blood, whereas CD28 signaling, but not TNF, was needed for chemotaxis of inflammatory monocytes into blood and lymphoid tissue. However, both pathways triggered local recruitment of neutrophils into lymph nodes. Thus, our findings revealed a dual mechanism of monocyte and neutrophil recruitment by T cells relying on overlapping and nonoverlapping roles for the noninducible costimulatory receptor CD28 and the inflammatory cytokine TNF. During sepsis, there might be clinical value in inhibiting CD28 signaling to decrease T cell-mediated inflammation and recruitment of innate cells while retaining bioactive TNF to foster neutrophil circulation. PMID- 27183625 TI - The Complement C3a Receptor Contributes to Melanoma Tumorigenesis by Inhibiting Neutrophil and CD4+ T Cell Responses. AB - The complement peptide C3a is a key component of the innate immune system and a major fragment produced following complement activation. We used a murine model of melanoma (B16-F0) to identify a hitherto unknown role for C3a-C3aR signaling in promoting tumor growth. The results show that the development and growth of B16-F0 melanomas is retarded in mice lacking C3aR, whereas growth of established melanomas can be arrested by C3aR antagonism. Flow cytometric analysis showed alterations in tumor-infiltrating leukocytes in the absence of C3aR. Specifically, neutrophils and CD4(+) T lymphocyte subpopulations were increased, whereas macrophages were reduced. The central role of neutrophils was confirmed by depletion experiments that reversed the tumor inhibitory effects observed in C3aR-deficient mice and returned tumor-infiltrating CD4(+) T cells to control levels. Analysis of the tumor microenvironment showed upregulation of inflammatory genes that may contribute to the enhanced antitumor response observed in C3aR-deficient mice. C3aR deficiency/inhibition was also protective in murine models of BRAF(V600E) mutant melanoma and colon and breast cancer, suggesting a tumor-promoting role for C3aR signaling in a range of tumor types. We propose that C3aR activation alters the tumor inflammatory milieu, thereby promoting tumor growth. Therapeutic inhibition of C3aR may therefore be an effective means to trigger an antitumor response in melanoma and other cancers. PMID- 27183626 TI - LSm14A Plays a Critical Role in Antiviral Immune Responses by Regulating MITA Level in a Cell-Specific Manner. AB - Viral infection triggers induction of antiviral cytokines and effectors, which are critical mediators of innate antiviral immune response. It has been shown that the processing body-associated protein LSm14A is involved in the induction of antiviral cytokines in cell lines but in vivo evidence is lacking. By generating LSm14A-deficient mice, in this study, we show that LSm14A plays a critical and specific role in the induction of antiviral cytokines in dendritic cells (DCs) but not in macrophages and fibroblasts. Induction of antiviral cytokines triggered by the DNA viruses HSV-1 and murid herpesvirus 68 and the RNA virus vesicular stomatitis virus but not Sendai virus was impaired in Lsm14a(-/-) DCs, which is correlated to the functions of the adaptor protein MITA/STING in the antiviral signaling pathways. LSm14A deficiency specifically downregulated MITA/STING level in DCs by impairing its nuclear mRNA precursor processing and subsequently impaired antiviral innate and adaptive immune responses. Our findings reveal a nuclear mRNA precursor processing and cell-specific regulatory mechanism of antiviral immune responses. PMID- 27183623 TI - Tbet or Continued RORgammat Expression Is Not Required for Th17-Associated Immunopathology. AB - The discovery of Th17 cell plasticity, in which CD4(+) IL-17-producing Th17 cells give rise to IL-17/IFN-gamma double-producing cells and Th1-like IFNgamma(+) ex Th17 lymphocytes, has raised questions regarding which of these cell types contribute to immunopathology during inflammatory diseases. In this study, we show using Helicobacter hepaticus-induced intestinal inflammation that IL 17A(Cre)- or Rag1(Cre)-mediated deletion of Tbx21 has no effect on the generation of IL-17/IFN-gamma double-producing cells, but leads to a marked absence of Th1 like IFNgamma(+) ex-Th17 cells. Despite the lack of Th1-like ex-Th17 cells, the degree of H. hepaticus-triggered intestinal inflammation in mice in which Tbx21 was excised in IL-17-producing or Rag1-expressing cells is indistinguishable from that observed in control mice. In stark contrast, using experimental autoimmune encephalomyelitis, we show that IL-17A(Cre)-mediated deletion of Tbx21 prevents the conversion of Th17 cells to IL-17A/IFN-gamma double-producing cells as well as Th1-like IFN-gamma(+) ex-Th17 cells. However, IL-17A(Cre)-mediated deletion of Tbx21 has only limited effects on disease course in this model and is not compensated by Ag-specific Th1 cells. IL-17A(Cre)-mediated deletion of Rorc reveals that RORgammat is essential for the maintenance of the Th17 cell lineage, but not immunopathology during experimental autoimmune encephalomyelitis. These results show that neither the single Th17 subset, nor its progeny, is solely responsible for immunopathology or autoimmunity. PMID- 27183624 TI - IDO2 Modulates T Cell-Dependent Autoimmune Responses through a B Cell-Intrinsic Mechanism. AB - Mechanistic insight into how adaptive immune responses are modified along the self-nonself continuum may offer more effective opportunities to treat autoimmune disease, cancer, and other sterile inflammatory disorders. Recent genetic studies in the KRN mouse model of rheumatoid arthritis demonstrate that the immunomodulatory molecule IDO2 modifies responses to self-antigens; however, the mechanisms involved are obscure. In this study, we show that IDO2 exerts a critical function in B cells to support the generation of autoimmunity. In experiments with IDO2-deficient mice, adoptive transplant experiments demonstrated that IDO2 expression in B cells was both necessary and sufficient to support robust arthritis development. IDO2 function in B cells was contingent on a cognate, Ag-specific interaction to exert its immunomodulatory effects on arthritis development. We confirmed a similar requirement in an established model of contact hypersensitivity, in which IDO2-expressing B cells are required for a robust inflammatory response. Mechanistic investigations showed that IDO2 deficient B cells lacked the ability to upregulate the costimulatory marker CD40, suggesting IDO2 acts at the T-B cell interface to modulate the potency of T cell help needed to promote autoantibody production. Overall, our findings revealed that IDO2 expression by B cells modulates autoimmune responses by supporting the cross talk between autoreactive T and B cells. PMID- 27183627 TI - Inflammatory Signals Regulate IL-15 in Response to Lymphodepletion. AB - Induction of lymphopenia has been exploited therapeutically to improve immune responses to cancer therapies and vaccinations. Whereas IL-15 has well established roles in stimulating lymphocyte responses after lymphodepletion, the mechanisms regulating these IL-15 responses are unclear. We report that cell surface IL-15 expression is upregulated during lymphopenia induced by total body irradiation (TBI), cyclophosphamide, or Thy1 Ab-mediated T cell depletion, as well as in RAG(-/-) mice; interestingly, the cellular profile of surface IL-15 expression is distinct in each model. In contrast, soluble IL-15 (sIL-15) complexes are upregulated only after TBI or alphaThy1 Ab. Analysis of cell specific IL-15Ralpha conditional knockout mice revealed that macrophages and dendritic cells are important sources of sIL-15 complexes after TBI but provide minimal contribution in response to Thy1 Ab treatment. Unlike with TBI, induction of sIL-15 complexes by alphaThy1 Ab is sustained and only partially dependent on type I IFNs. The stimulator of IFN genes pathway was discovered to be a potent inducer of sIL-15 complexes and was required for optimal production of sIL-15 complexes in response to Ab-mediated T cell depletion and TBI, suggesting products of cell death drive production of sIL-15 complexes after lymphodepletion. Lastly, we provide evidence that IL-15 induced by inflammatory signals in response to lymphodepletion drives lymphocyte responses, as memory CD8 T cells proliferated in an IL-15-dependent manner. Overall, these studies demonstrate that the form in which IL-15 is expressed, its kinetics and cellular sources, and the inflammatory signals involved are differentially dictated by the manner in which lymphopenia is induced. PMID- 27183629 TI - Activation of Plasmacytoid Dendritic Cells in Colon-Draining Lymph Nodes during Citrobacter rodentium Infection Involves Pathogen-Sensing and Inflammatory Pathways Distinct from Conventional Dendritic Cells. AB - Dendritic cells (DCs) bear the main responsibility for initiation of adaptive immune responses necessary for antimicrobial immunity. In the small intestine, afferent lymphatics convey Ags and microbial signals to mesenteric lymph nodes (LNs) to induce adaptive immune responses against microbes and food Ags derived from the small intestine. Whether the large intestine is covered by the same lymphatic system or represents its own lymphoid compartment has not been studied until very recently. We identified three small mesenteric LNs, distinct from small intestinal LNs, which drain lymph specifically from the colon, and studied DC responses to the attaching and effacing pathogen Citrobacter rodentium in these. Transcriptional profiling of conventional (CD11c(high)CD103(high)) DC and plasmacytoid (plasmacytoid DC Ag-1(high)B220(+)CD11c(int)) DC (pDC) populations during steady-state conditions revealed activity of distinct sets of genes in these two DC subsets, both in small intestinal and colon-draining LNs. C. rodentium activated DC especially in colon-draining LNs, and gene expression changed in pDC more profoundly than in conventional DC. Among the genes most upregulated in pDC were C-type lectin receptor CLEC4E, IL-1Rs (IL-1R1 and -2), proinflammatory cytokines (IL-1a and IL-6), and TLR6. Our results indicate that colon immune surveillance is distinct from that of the small intestine in terms of draining LNs, and identify pDC as active sentinels of colonic inflammation and/or microbial dysbiosis. PMID- 27183628 TI - Novel Teleost CD4-Bearing Cell Populations Provide Insights into the Evolutionary Origins and Primordial Roles of CD4+ Lymphocytes and CD4+ Macrophages. AB - Tetrapods contain a single CD4 coreceptor with four Ig domains that likely arose from a primordial two-domain ancestor. Notably, teleost fish contain two CD4 genes. Like tetrapod CD4, CD4-1 of rainbow trout includes four Ig domains, whereas CD4-2 contains only two. Because CD4-2 is reminiscent of the prototypic two-domain CD4 coreceptor, we hypothesized that by characterizing the cell types bearing CD4-1 and CD4-2, we would shed light into the evolution and primordial roles of CD4-bearing cells. Using newly established mAbs against CD4-1 and CD4-2, we identified two bona-fide CD4(+) T cell populations: a predominant lymphocyte population coexpressing surface CD4-1 and CD4-2 (CD4 double-positive [DP]), and a minor subset expressing only CD4-2 (CD4-2 single-positive [SP]). Although both subsets produced equivalent levels of Th1, Th17, and regulatory T cell cytokines upon bacterial infection, CD4-2 SP lymphocytes were less proliferative and displayed a more restricted TCRbeta repertoire. These data suggest that CD4-2 SP cells represent a functionally distinct population and may embody a vestigial CD4(+) T cell subset, the roles of which reflect those of primeval CD4(+) T cells. Importantly, we also describe the first CD4(+) monocyte/macrophage population in a nonmammalian species. Of all myeloid subsets, we found the CD4(+) population to be the most phagocytic, whereas CD4(+) lymphocytes lacked this capacity. This study fills in an important gap in the knowledge of teleost CD4 bearing leukocytes, thus revealing critical insights into the evolutionary origins and primordial roles of CD4(+) lymphocytes and CD4(+) monocytes/macrophages. PMID- 27183630 TI - ERbeta in CD4+ T Cells Is Crucial for Ligand-Mediated Suppression of Central Nervous System Autoimmunity. AB - The development of therapies for multiple sclerosis targeting pathogenic T cell responses remains imperative. Previous studies have shown that estrogen receptor (ER) beta ligands could inhibit experimental autoimmune encephalomyelitis. However, the effects of ERbeta-specific ligands on human or murine pathogenic immune cells, such as Th17, were not investigated. In this article, we show that the synthetic ERbeta-specific ligand 4-(2-phenyl-5,7 bis[trifluoromethyl]pyrazolo[1,5-a]pyrimidin-3-yl)phenol (PHTPP) reversed established paralysis and CNS inflammation, characterized by a dramatic suppression of pathogenic Th responses as well as induction of IL-10-producing regulatory CD4(+) T cell subsets in vivo. Moreover, administration of PHTPP in symptomatic mice induced regulatory CD4(+) T cells that were suppressive in vivo. PHTPP-mediated experimental autoimmune encephalomyelitis amelioration was canceled in mice with ERbeta-deficient CD4(+) T cells only, indicating that expression of ERbeta by these cells is crucial for the observed therapeutic effect. Importantly, synthetic ERbeta-specific ligands acting directly on CD4(+) T cells suppressed human and mouse Th17 cells, downregulating Th17 cell signature gene expression and expanding IL-10-producing T cells among them. TGF-beta1 and aryl hydrocarbon receptor activation enhanced the ERbeta ligand-mediated expansion of IL-10-producing T cells among Th17 cells. In addition, these ERbeta specific ligands promoted the induction and maintenance of Foxp3(+) T regulatory cells, as well as their in vitro suppressive function. Thus, ERbeta-specific ligands targeting pathogenic Th17 cells and inducing functional regulatory cells represent a promising subset of therapeutic agents for multiple sclerosis. PMID- 27183632 TI - Multiple IgH Isotypes Including IgD, Subclasses of IgM, and IgY Are Expressed in the Common Ancestors of Modern Birds. AB - Although evolutionarily just as ancient as IgM, it has been thought for many years that IgD is not present in birds. Based on the recently sequenced genomes of 48 bird species as well as high-throughput transcriptome sequencing of immune related tissues, we demonstrate in this work that the ostrich (Struthio camelus) possesses a functional delta gene that encodes a membrane-bound IgD H chain with seven CH domains. Furthermore, delta sequences were clearly identified in many other bird species, demonstrating that the delta gene is widely distributed among birds and is only absent in certain bird species. We also show that the ostrich possesses two MU genes (MU1, MU2) and two upsilon genes (upsilon1, upsilon2), in addition to the delta and alpha genes. Phylogenetic analyses suggest that subclass diversification of both the MU and upsilon genes occurred during the early stages of bird evolution, after their divergence from nonavian reptiles. Although the positions of the two upsilon genes are unknown, physical mapping showed that the remaining genes are organized in the order MU1-delta-alpha-MU2, with the alpha gene being inverted relative to the others. Together with previous studies, our data suggest that birds and nonavian reptile species most likely shared a common ancestral IgH gene locus containing a delta gene and an inverted alpha gene. The delta gene was then evolutionarily lost in selected birds, whereas the alpha gene lost in selected nonavian reptiles. The data obtained in this study provide significant insights into the understanding of IgH gene evolution in tetrapods. PMID- 27183631 TI - M-CSF Mediates Host Defense during Bacterial Pneumonia by Promoting the Survival of Lung and Liver Mononuclear Phagocytes. AB - Gram-negative bacterial pneumonia is a common and dangerous infection with diminishing treatment options due to increasing antibiotic resistance among causal pathogens. The mononuclear phagocyte system is a heterogeneous group of leukocytes composed of tissue-resident macrophages, dendritic cells, and monocyte derived cells that are critical in defense against pneumonia, but mechanisms that regulate their maintenance and function during infection are poorly defined. M CSF has myriad effects on mononuclear phagocytes but its role in pneumonia is unknown. We therefore tested the hypothesis that M-CSF is required for mononuclear phagocyte-mediated host defenses during bacterial pneumonia in a murine model of infection. Genetic deletion or immunoneutralization of M-CSF resulted in reduced survival, increased bacterial burden, and greater lung injury. M-CSF was necessary for the expansion of lung mononuclear phagocytes during infection but did not affect the number of bone marrow or blood monocytes, proliferation of precursors, or recruitment of leukocytes to the lungs. In contrast, M-CSF was essential to survival and antimicrobial functions of both lung and liver mononuclear phagocytes during pneumonia, and its absence resulted in bacterial dissemination to the liver and hepatic necrosis. We conclude that M CSF is critical to host defenses against bacterial pneumonia by mediating survival and antimicrobial functions of mononuclear phagocytes in the lungs and liver. PMID- 27183633 TI - Phase-Variable Heptose I Glycan Extensions Modulate Efficacy of 2C7 Vaccine Antibody Directed against Neisseria gonorrhoeae Lipooligosaccharide. AB - Neisseria gonorrhoeae, the causative agent of the sexually transmitted infection, gonorrhea, has developed resistance to most conventional antibiotics. Safe and effective vaccines against gonorrhea are needed urgently. A candidate vaccine that targets a lipooligosaccharide (LOS) epitope recognized mAb 2C7 attenuates gonococcal burden in the mouse vaginal colonization model. Glycan extensions from the LOS core heptoses (HepI and HepII) are controlled by phase-variable LOS glycosyltransferase (lgt) genes; we sought to define how HepI glycan extensions affect mAb 2C7 function. Isogenic gonococcal mutants in which the lgt required for mAb 2C7 reactivity (lgtG) was genetically locked on and the lgt loci required for HepI variation (lgtA, lgtC, and lgtD) were genetically locked on or off in different combinations were created. We observed 100% complement-dependent killing by mAb 2C7 of a mutant that expressed lactose (Gal-Glc) from HepI, whereas a mutant that expressed Gal-Gal-Glc-HepI fully resisted killing (>100% survival). Mutants that elaborated 4- (Gal-GlcNAc-Gal-Glc-HepI) and 5-glycan (GalNAc-Gal-GlcNAc-Gal-Glc-HepI) structures displayed intermediate phenotypes (<50% killing with 2 MUg/ml and >95% killing with 4 MUg/ml mAb 2C7). The contrasting phenotypes of the lactose-HepI and the Gal-Gal-Glc-HepI LOS structures were recapitulated with phase variants of a recently isolated clinical strain. Despite lack of killing of the Gal-Gal-Glc-HepI mutants, mAb 2C7 deposited sufficient C3 on these bacteria for opsonophagocytic killing by human neutrophils. In conclusion, mAb 2C7 showed functional activity against all gonococcal HepI LOS structures defined by various lgtA/C/D on/off combinations, thereby providing further impetus for use of the 2C7 epitope in a gonococcal vaccine. PMID- 27183636 TI - Prolonged Intake of Dietary Lipids Alters Membrane Structure and T Cell Responses in LDLr-/- Mice. AB - Although it is recognized that lipids and membrane organization in T cells affect signaling and T cell activation, to what extent dietary lipids alter T cell responsiveness in the absence of obesity and inflammation is not known. In this study, we fed low-density lipoprotein receptor knockout mice a Western high-fat diet for 1 or 9 wk and examined T cell responses in vivo along with T cell lipid composition, membrane order, and activation ex vivo. Our data showed that high levels of circulating lipids for a prolonged period elevated CD4(+) and CD8(+) T cell proliferation and resulted in an increased proportion of CD4(+) central memory T cells within the draining lymph nodes following induction of contact hypersensitivity. In addition, the 9-wk Western high-fat diet elevated the total phospholipid content and monounsaturated fatty acid level, but decreased saturated phosphatidylcholine and sphingomyelin within the T cells. The altered lipid composition in the circulation, and of T cells, was also reflected by enhanced membrane order at the activation site of ex vivo activated T cells that corresponded to increased IL-2 mRNA levels. In conclusion, dietary lipids can modulate T cell lipid composition and responses in lipoprotein receptor knockout mice even in the absence of excess weight gain and a proinflammatory environment. PMID- 27183634 TI - Ubiquitin Ligases and Deubiquitinating Enzymes in CD4+ T Cell Effector Fate Choice and Function. AB - The human body is exposed to potentially pathogenic microorganisms at barrier sites such as the skin, lungs, and gastrointestinal tract. To mount an effective response against these pathogens, the immune system must recruit the right cells with effector responses that are appropriate for the task at hand. Several types of CD4(+) T cells can be recruited, including Th cells (Th1, Th2, and Th17), T follicular helper cells, and regulatory T cells. These cells help to maintain normal immune homeostasis in the face of constantly changing microbes in the environment. Because these cells differentiate from a common progenitor, the composition of their intracellular milieu of proteins changes to appropriately guide their effector function. One underappreciated process that impacts the levels and functions of effector fate-determining factors is ubiquitylation. This review details our current understanding of how ubiquitylation regulates CD4(+) T cell effector identity and function. PMID- 27183635 TI - Alloimmunity and Tolerance in Corneal Transplantation. AB - Corneal transplantation is one of the most prevalent and successful forms of solid tissue transplantation. Despite favorable outcomes, immune-mediated graft rejection remains the major cause of corneal allograft failure. Although low-risk graft recipients with uninflamed graft beds enjoy a success rate ~90%, the rejection rates in inflamed graft beds or high-risk recipients often exceed 50%, despite maximal immune suppression. In this review, we discuss the critical facets of corneal alloimmunity, including immune and angiogenic privilege, mechanisms of allosensitization, cellular and molecular mediators of graft rejection, and allotolerance induction. PMID- 27183638 TI - Dok1 and Dok2 Proteins Regulate Cell Cycle in Hematopoietic Stem and Progenitor Cells. AB - Dok1 and Dok2 proteins play a crucial role in myeloid cell proliferation as demonstrated by Dok1 and Dok2 gene inactivation, which induces a myeloproliferative disease in aging mice. In this study, we show that Dok1/Dok2 deficiency affects myeloproliferation even at a young age. An increase in the cellularity of multipotent progenitors is observed in young Dok1/Dok2-deficient mice. This is associated with an increase in the cells undergoing cell cycle, which is restricted to myeloid committed progenitors. Furthermore, cellular stress triggered by 5-fluorouracil (5-FU) treatment potentiates the effects of the loss of Dok proteins on multipotent progenitor cell cycle. In addition, Dok1/Dok2 deficiency induces resistance to 5-FU-induced hematopoietic stem cell exhaustion. Taken together, these results demonstrate that Dok1 and Dok2 proteins are involved in the control of hematopoietic stem cell cycle regulation. PMID- 27183637 TI - Production of Proinflammatory Cytokines by Monocytes in Liver-Transplanted Recipients with De Novo Autoimmune Hepatitis Is Enhanced and Induces TH1-like Regulatory T Cells. AB - A subset of human regulatory T cells (Tregs) can secrete IFN-gamma or IL-17, and thus share features of TH1 or TH17 effector cells and lose suppressive function. The main factors driving this differentiation of Tregs toward a proinflammatory phenotype include IL-12 for TH1-like and IL-6 for TH17-type Tregs. In this study we show that Tregs of patients with de novo autoimmune hepatitis (dAIH) display increased frequencies of proinflammatory IFN-gamma and IL-17 cytokines. Irrespective of a fully demethylated FOXP3 locus, Tregs of subjects with dAIH are functionally impaired. In line with the observed Treg phenotype, we detected the presence of two dominant cytokines (IL-12 and IL-6) clustering with CD68(+) monocyte/macrophage cells in livers of subjects with dAIH, and isolated monocytes of subjects with dAIH secrete high levels of proinflammatory IL-12 and IL-6, suggesting that this inflammatory milieu is key for functional impairment of Tregs. Importantly, the blockade of IFN-gamma partially restores suppressive function of Tregs of subjects with dAIH, indicating that monocyte/macrophage derived triggers might play a central role in Treg dysfunction and pathogenesis of dAIH. PMID- 27183639 TI - NK Cells Help Induce Anti-Hepatitis B Virus CD8+ T Cell Immunity in Mice. AB - Although recent clinical studies demonstrate that NK cell function is impaired in hepatitis B virus (HBV)-persistent patients, whether or how NK cells play a role in anti-HBV adaptive immunity remains to be explored. Using a mouse model mimicking acute HBV infection by hydrodynamic injection of an HBV plasmid, we observed that although serum hepatitis B surface Ag and hepatitis B envelope Ag were eliminated within 3 to 4 wk, HBV might persist for >8 wk in CD8(-/-) mice and that adoptive transfer of anti-HBV CD8(+) T cells restored the ability to clear HBV in HBV-carrier Rag1(-/-) mice. These results indicate that CD8(+) T cells are critical in HBV elimination. Furthermore, NK cells increased IFN-gamma production after HBV plasmid injection, and NK cell depletion led to significantly increased HBV persistence along with reduced frequency of hepatitis B core Ag-specific CD8(+) T cells. Adoptive transfer of IFN-gamma-sufficient NK cells restored donor CD8(+) T cell function, indicating that NK cells positively regulated CD8(+) T cells via secreting IFN-gamma. We also observed that NK cell depletion correlated with decreased effector memory CD8(+) T cell frequencies. Importantly, adoptive transfer experiments showed that NK cells were involved in anti-HBV CD8(+) T cell recall responses. Moreover, DX5(+)CD49a(-) conventional, but not DX5(-)CD49a(+) liver-resident, NK cells were involved in improving CD8(+) T cell responses against HBV. Overall, the current study reveals that NK cells, especially DX5(+)CD49a(-) conventional NK cells, promote the antiviral activity of CD8(+) T cell responses via secreting IFN-gamma in a mouse model mimicking acute HBV infection. PMID- 27183640 TI - Dopamine Receptor D3 Signaling on CD4+ T Cells Favors Th1- and Th17-Mediated Immunity. AB - Dopamine receptor D3 (DRD3) expressed on CD4(+) T cells is required to promote neuroinflammation in a murine model of Parkinson's disease. However, how DRD3 signaling affects T cell-mediated immunity remains unknown. In this study, we report that TCR stimulation on mouse CD4(+) T cells induces DRD3 expression, regardless of the lineage specification. Importantly, functional analyses performed in vivo using adoptive transfer of OVA-specific OT-II cells into wild type recipients show that DRD3 deficiency in CD4(+) T cells results in attenuated differentiation of naive CD4(+) T cells toward the Th1 phenotype, exacerbated generation of Th2 cells, and unaltered Th17 differentiation. The reciprocal regulatory effect of DRD3 signaling in CD4(+) T cells favoring Th1 generation and impairing the acquisition of Th2 phenotype was also reproduced using in vitro approaches. Mechanistic analysis indicates that DRD3 signaling evokes suppressor of cytokine signaling 5 expression, a negative regulator of Th2 development, which indirectly favors acquisition of Th1 phenotype. Accordingly, DRD3 deficiency results in exacerbated eosinophil infiltration into the airways of mice undergoing house dust mite-induced allergic response. Interestingly, our results show that, upon chronic inflammatory colitis induced by transfer of naive CD4(+) T cells into lymphopenic recipients, DRD3 deficiency not only affects Th1 response, but also the frequency of Th17 cells, suggesting that DRD3 signaling also contributes to Th17 expansion under chronic inflammatory conditions. In conclusion, our findings indicate that DRD3-mediated signaling in CD4(+) T cells plays a crucial role in the balance of effector lineages, favoring the inflammatory potential of CD4(+) T cells. PMID- 27183641 TI - Helicobacter pylori gamma-Glutamyltranspeptidase Induces Tolerogenic Human Dendritic Cells by Activation of Glutamate Receptors. AB - Helicobacter pylori infection is characterized by chronic persistence of the bacterium. Different virulence factors, including H. pylori gamma glutamyltranspeptidase (gGT), have been reported to induce tolerogenicity by reprogramming dendritic cells (DCs). gGT is present in all bacterial isolates, indicating an important role for gGT in the course of infection. In the current study, we have analyzed the effect of H. pylori gGT on human DCs and the subsequent adaptive immune response. We show that glutamate produced due to H. pylori gGT enzymatic activity tolerizes DCs by inhibiting cAMP signaling and dampening IL-6 secretion in response to the infection. Together, our results provide a novel molecular mechanism by which H. pylori manipulates the host's immune response to persist within its host. PMID- 27183642 TI - Immunodominant West Nile Virus T Cell Epitopes Are Fewer in Number and Fashionably Late. AB - Class I HLA molecules mark infected cells for immune targeting by presenting pathogen-encoded peptides on the cell surface. Characterization of viral peptides unique to infected cells is important for understanding CD8(+) T cell responses and for the development of T cell-based immunotherapies. Having previously reported a series of West Nile virus (WNV) epitopes that are naturally presented by HLA-A*02:01, in this study we generated TCR mimic (TCRm) mAbs to three of these peptide/HLA complexes-the immunodominant SVG9 (E protein), the subdominant SLF9 (NS4B protein), and the immunorecessive YTM9 (NS3 protein)-and used these TCRm mAbs to stain WNV-infected cell lines and primary APCs. TCRm staining of WNV infected cells demonstrated that the immunorecessive YTM9 appeared several hours earlier and at 5- to 10-fold greater density than the more immunogenic SLF9 and SVG9 ligands, respectively. Moreover, staining following inhibition of the TAP demonstrated that all three viral ligands were presented in a TAP-dependent manner despite originating from different cellular compartments. To our knowledge, this study represents the first use of TCRm mAbs to define the kinetics and magnitude of HLA presentation for a series of epitopes encoded by one virus, and the results depict a pattern whereby individual epitopes differ considerably in abundance and availability. The observations that immunodominant ligands can be found at lower levels and at later time points after infection suggest that a reevaluation of the factors that combine to shape T cell reactivity may be warranted. PMID- 27183644 TI - Ptk7-Deficient Mice Have Decreased Hematopoietic Stem Cell Pools as a Result of Deregulated Proliferation and Migration. AB - Hematopoietic stem cells (HSCs) located in adult bone marrow or fetal liver in mammals produce all cells from the blood system. At the top of the hierarchy are long-term HSCs endowed with lifelong self-renewal and differentiation properties. These features are controlled through key microenvironmental cues and regulatory pathways, such as Wnt signaling. We showed previously that PTK7, a tyrosine kinase receptor involved in planar cell polarity, plays a role in epithelial Wnt signaling; however, its function in hematopoiesis has remained unexplored. In this article, we show that PTK7 is expressed by hematopoietic stem and progenitor cells, with the highest level of protein expression found on HSCs. Taking advantage of a Ptk7-deficient mouse strain, we demonstrate that loss of Ptk7 leads to a diminished pool of HSCs but does not affect in vitro or in vivo hematopoietic cell differentiation. This is correlated with increased quiescence and reduced homing abilities of Ptk7-deficient hematopoietic stem and progenitor cells, unraveling novel and unexpected functions for planar cell polarity pathways in HSC fate. PMID- 27183643 TI - Age-Related Decline in Natural IgM Function: Diversification and Selection of the B-1a Cell Pool with Age. AB - Streptococcus pneumoniae is the most common cause of pneumonia, which claims the lives of people over the age of 65 y seven times more frequently than those aged 5-49 y. B-1a cells provide immediate and essential protection from S. pneumoniae through production of natural Ig, which has minimal insertion of N-region additions added by the enzyme TdT. In experiments with SCID mice infected with S. pneumoniae, we found passive transfer of IgG-depleted serum from aged (18-24 mo old) mice had no effect whereas IgG-depleted serum from young (3 mo old) mice was protective. This suggests protective natural IgM changes with age. Using single cell PCR we found N-region addition, which is initially low in fetal-derived B-1a cell IgM developing in the absence of TdT, increased in 7- to 24-mo-old mice as compared with 3-mo-old mice. To determine the mechanism responsible for the age related change in B-1a cell IgM, we established a mixed chimera system in which mice were reconstituted with allotype-marked mature peritoneal B-1a cells and adult bone marrow cells. We demonstrated even in the presence of mature peritoneal B-1a cells, adult bone marrow contributed to the mature B-1a cell pool. More importantly, using this system we found over a 10-mo-period peritoneal B-1a cell IgM changed, showing the number of cells lacking N-region additions at both junctions fell from 49 to 29% of sequences. These results strongly suggest selection-induced skewing alters B-1a cell-derived natural Ab, which may in turn be responsible for the loss of natural IgM-mediated protection against pneumococcal infection. PMID- 27183645 TI - The Opportunity To Eradicate Peste des Petits Ruminants. AB - Peste des petits ruminants (PPR) is a highly infectious disease of sheep and goats that is caused by PPR virus, a member of the genus Morbillivirus that includes the viruses that cause rinderpest (RP) in cattle. RP was the first animal disease to be globally eradicated in 2011 and is only the second disease, after smallpox, to have ever been eradicated. PPR is one of the principal constraints to small ruminant production in Africa, Asia, and the Middle East. The epidemiology of PPR and RP as well as the technologies available for their diagnosis and control are similar. The conditions that favored the eradication of RP are also largely present for PPR. In this work, we outline the evolving strategy for eradication in light of current opportunities and challenges, as well as the lessons from other eradication programs in animal and human health. The global PPR situation and technology for its control are summarized. A strategy based on the lessons from previous eradication efforts that integrate epidemiology, social science, and economics as tools to target and motivate vaccination is summarized. Major aspects of the cost and benefit-cost analysis of the indicated program are presented. The overall undiscounted cost of eradication was estimated as $3.1 billion, and the benefit-cost ratio for the most likely scenario was estimated at 33.8. We close with a discussion of the possible next steps. PMID- 27183646 TI - Discovery of the gammadelta TCR: Act II. PMID- 27183647 TI - Pillars Article: Identification of a Putative Second T-cell Receptor. Nature. 1986. 322: 145-149. PMID- 27183648 TI - Pillars Article: A Functional T3 Molecule Associated with a Novel Heterodimer on the Surface of Immature Human Thymocytes. Nature. 1986. 322: 179-181. PMID- 27183650 TI - Correction: Immunological Priming Requires Regulatory T Cells and IL-10-Producing Macrophages To Accelerate Resolution from Severe Lung Inflammation. PMID- 27183649 TI - Assembly and Expression of Shark Ig Genes. AB - Sharks are modern descendants of the earliest vertebrates possessing Ig superfamily receptor-based adaptive immunity. They respond to immunogen with Abs that, upon boosting, appear more rapidly and show affinity maturation. Specific Abs and immunological memory imply that Ab diversification and clonal selection exist in cartilaginous fish. Shark Ag receptors are generated through V(D)J recombination, and because it is a mechanism known to generate autoreactive receptors, this implies that shark lymphocytes undergo selection. In the mouse, the ~2.8-Mb IgH and IgL loci require long-range, differential activation of component parts for V(D)J recombination, allelic exclusion, and receptor editing. These processes, including class switching, evolved with and appear inseparable from the complex locus organization. In contrast, shark Igs are encoded by 100 200 autonomously rearranging miniloci. This review describes how the shark primary Ab repertoire is generated in the absence of structural features considered essential in mammalian Ig gene assembly and expression. PMID- 27183651 TI - Correction: CD4+ Group 1 Innate Lymphoid Cells (ILC) Form a Functionally Distinct ILC Subset That Is Increased in Systemic Sclerosis. PMID- 27183652 TI - Correction: Yeast-Derived Particulate beta-Glucan Treatment Subverts the Suppression of Myeloid-Derived Suppressor Cells (MDSC) by Inducing Polymorphonuclear MDSC Apoptosis and Monocytic MDSC Differentiation to APC in Cancer. PMID- 27183654 TI - Correction: Targeting of Antigens to B Lymphocytes via CD19 as a Means for Tumor Vaccine Development. PMID- 27183653 TI - Correction: Dectin-1 Activation by a Natural Product beta-Glucan Converts Immunosuppressive Macrophages into an M1-like Phenotype. PMID- 27183655 TI - Predicting intraprocedural rupture and thrombus formation during coiling of ruptured anterior communicating artery aneurysms. AB - BACKGROUND: Intraprocedural rupture and thrombus formation are serious complications during coiling of ruptured intracranial aneurysms, and they more often occur in patients with anterior communicating artery (ACoA) aneurysms. OBJECTIVE: To identify independent predictors of intraprocedural rupture and thrombus formation during coiling of ruptured ACoA aneurysms. METHODS: Between January 2008 and February 2015, 254 consecutive patients with 255 ACoA aneurysms were treated with coiling. We retrospectively reviewed intraoperative angiograms and medical records to identify intraprocedural rupture and thrombus formation, and re-measured aneurysm morphologies using CT angiography images. Multivariate logistic regression models were used to determine independent predictors of intraprocedural rupture and thrombus formation. RESULTS: Of the 231 patients included, intraprocedural rupture occurred in 10 (4.3%) patients, and thrombus formation occurred in 15 (6.5%) patients. Patients with smaller aneurysms more often experienced intraprocedural rupture than those with larger aneurysms (3.5+/ 1.3 mm vs 5.7+/-2.3 mm). Multivariate analysis showed that smaller ruptured aneurysms (p=0.003) were independently associated with intraprocedural rupture. The threshold of aneurysm size separating rupture and non-rupture groups was 3.5 mm. Multivariate analysis showed that a history of hypertension (p=0.033), aneurysm neck size (p=0.004), and parent vessel angle (p=0.023) were independent predictors of thrombus formation. The threshold of parent vessel angle separating thrombus and non-thrombus groups was 60.0 degrees . CONCLUSIONS: Ruptured aneurysms <3.5 mm were associated with an increased risk of intraprocedural rupture, and parent vessel angle <60.0 degrees , wider-neck aneurysms, and a history of hypertension were associated with increased risk of thrombus formation during coiling of ruptured ACoA aneurysms. PMID- 27183656 TI - [Patients seldom talk about complementary medicine]. PMID- 27183657 TI - [Quarterly accounting submissions have no time limits]. PMID- 27183658 TI - [Mail to the statuary insurance can be billed according to EBM, patient letter at best according to GOA. ]. PMID- 27183659 TI - [At what point is a wound considered "large"]. PMID- 27183660 TI - [Not Available]. PMID- 27183661 TI - ["I must stand still 3 times on the way to the subway"]. PMID- 27183663 TI - [Positive vote for hypericum therapy is reaffirmed]. PMID- 27183662 TI - [Effect of dapagliflozin on cardiovascular risk factors]. PMID- 27183664 TI - [Brief notes. Approval recommendation for fixed combination Descovy(R) in treatment of HIV]. PMID- 27183665 TI - [Distribution of waist circumference and waist-to-height ratio and their values in obesity screening among 3-9 years old Han and Uygur ethnic children in Xinjiang Uygur Autonomous Region of China]. AB - OBJECTIVE: To understand the distributions of waist circumference and waist-to height ratio (WHtR) in Han and Uygur ethnic children aged 3-9 years in Xinjiang Uygur Autonomous Region (Xinjiang) and discuss their values in obesity screening in children. METHODS: Stratified cluster random sampling was conducted to select Han and Uygur ethnic children from kindergartens and primary schools in four areas of Xinjiang in April 2014. The children's standing height, body weight and waist circumference were measured by trained investigators according to standard protocol. WC>or=P80 and WHtR>or=0.48 were used as the cutoff value for abdominal obesity screening in children with normal BMI. The association between overweight/obese prevalence rate and obesity related indicators, such as BMI, WC, WHtR, were analyzed. RESULTS: A total of 4024 Han and Uygur ethnic children were investigated, in which 2461 were in Han ethnic group, 1563 were in Uygur ethnic group. The WC and WHtR at P50 and P80 were differed significantly. In both Han and Uygur ethnic groups, there were some children with WC>or=P80 or WHtR>or=0.48, although they had normal BMI. This proportion decreased with age. CONCLUSIONS: The WC and WHtR are similar in Han and Uygur ethnic children aged 3-9 years. WC and WHtR have values in obesity screening for children with normal BMI which suggested to use it as the supplementation of BMI in obesity screening in preschool aged children. PMID- 27183666 TI - Improving access for disabled women. PMID- 27183667 TI - Butler's political action offends the prudish. PMID- 27183668 TI - Unions lose their effectiveness. PMID- 27183669 TI - Nurses' fears unfounded. PMID- 27183670 TI - Thought-provoking articles. PMID- 27183671 TI - Don't put us out to pasture! PMID- 27183674 TI - The Kaiwhakahaere comments:. PMID- 27183672 TI - Article insults nurses' hard work. PMID- 27183677 TI - Bonding scheme places limited this year. PMID- 27183679 TI - Survey shows some improvement in Cantabrians' mental health. PMID- 27183682 TI - Nurses providing support in Fiji. PMID- 27183680 TI - Equal pay agreement this month? PMID- 27183683 TI - DHB funding cuts threaten staff wages. PMID- 27183684 TI - NP assessment held on marae for first time. PMID- 27183685 TI - Migrant nurses meet. PMID- 27183687 TI - Nurses share earthquake experiences. PMID- 27183688 TI - Primary care funding changes mooted. PMID- 27183689 TI - Helping women facing cancer. PMID- 27183690 TI - So what's a clinical nurse specialist exactly? PMID- 27183692 TI - Challenges remain for NPs, despite positive perceptions. PMID- 27183691 TI - Family Planning--an evolving service. PMID- 27183693 TI - Caring for women and their unborn babies. PMID- 27183694 TI - Juggling nursing and family care. PMID- 27183695 TI - Being videoed on the job. PMID- 27183696 TI - 'Why we need supervision'. PMID- 27183697 TI - Advancing NZNO's aims together. PMID- 27183698 TI - TPPA nurse protestor unlikety to lose her job. PMID- 27183702 TI - Respiratory nursing: New technology trialled on the ward. PMID- 27183703 TI - Living wage set at $19.80 an hour. PMID- 27183704 TI - Topical hydrocortisone 17-butyrate 21-propionate in the treatment of inflammatory skin diseases: pharmacological data, clinical efficacy, safety and calculation of the therapeutic index. AB - Hydrocortisone 17-butyrate 21-propionate (hydrocortisone buteprate, HBP) is a medium potent, non-halogenated double-ester of hydrocortisone with a favorable benefit/risk ratio for the treatment of inflammatory skin disorders. HBP is available as a 0.1% cream or ointment formulation. Good results were obtained with a once-daily topical treatment. HBP is characterized by a strong topical anti-inflammatory activity and weak systemic action. It is considered to have potency comparable to that of betamethasone 17-valerate (BV), but its systemic effects are less pronounced. HBP was shown to have a good efficacy in the treatment of various oozing and lichenified eczematous skin diseases including atopic dermatitis (AD) and in the treatment of psoriasis vulgaris. Even in very young children, HBP proved successful as an effective and safe drug. A therapeutic index of 2.0 can be attributed to this glucocorticoid. In this respect, there is no difference between topical HBP and other topical glucocorticoids with increased benefit/risk ratio, e.g. prednicarbate (PC), methylprednisolone aceponate (MPA) and mometasone furoate (MM). PMID- 27183705 TI - Physicochemical characterisation of fluids and soft foods frequently mixed with oral drug formulations prior to administration to children. AB - Oral drug administration to children poses specific pharmaceutical challenges that are often not seen to the same extent in adults, and whose occurrence may also be age dependent. When an age-appropriate dosage form is not available, manipulation of adult dosage forms (e.g., splitting and crushing of tablets or opening of capsules) has been reported as a means to facilitate administration to children. To enhance swallowability and/or mask an unpleasant taste of the dosage form to be administered, crushed/split tablets or the contents of capsules are often mixed with food or drinks or suspended in a vehicle prior to administration. However, it seems that the risks and benefits of an approach whereby the dosage form is modified prior to administration in this manner are everything but clear. The aim of the present study was to gain an overview of the physicochemical properties of a number of fluids, soft foods and suspension vehicles that are commonly reported to be mixed with oral medications before administration to children to improve patient acceptability. For this purpose, physicochemical parameters of 15 different fluids, soft foods and suspension vehicles were measured. These included pH, buffer capacity, osmolality, surface tension and viscosity. Results of the study clearly show the differences in physicochemical properties of the test candidates. It is thus obvious that the type of fluid/food mixed with a drug product before administration may have a significant impact on bioavailability of the drug administered. Therefore, a risk based assessment of such practices considering API properties, formulation features and physicochemical properties of the fluids and foods intended to be co administered with the dosage form, in conjunction with the anatomical and physiological maturity of the gastro-intestinal tract in the intended paediatric population, should be an essential part of paediatric oral formulation development. PMID- 27183706 TI - Development of a floating drug delivery system with superior buoyancy in gastric fluid using hot-melt extrusion coupled with pressurized CO2. AB - The present study aimed to develop a continuous single-step manufacturing platform to prepare a porous, low-density, and floating multi-particulate system (mini-tablet, 4 mm size). This process involves injecting inert, non-toxic pressurized CO2gas (P-CO2) in zone 4 of a 16-mm hot-melt extruder (HME) to continuously generate pores throughout the carrier matrix. Unlike conventional methods for preparing floating drug delivery systems, additional chemical excipients and additives are not needed in this approach to create minute openings on the surface of the matrices. The buoyancy efficiency of the prepared floating system (injection of P-CO2) in terms of lag time (0 s) significantly improved (P < 0.05), compared to the formulation prepared by adding the excipient sodium bicarbonate (lag time 120 s). The main advantages of this novel manufacturing technique include: (i) no additional chemical excipients need to be incorporated in the formulation, (ii) few manufacturing steps are required, (iii) high buoyancy efficiency is attained, and (iv) the extrudate is free of toxic solvent residues. Floating mini-tablets containing acetaminophen (APAP) as a model drug within the matrix-forming carrier (Eudragit(r) RL PO) have been successfully processed via this combined technique (P-CO2/HME). Desired controlled release profile of APAP from the polymer Eudragit(r) RL PO is attained in the optimized formulation, which remains buoyant on the surface of gastric fluids prior to gastric emptying time (average each 4 h). PMID- 27183707 TI - Skin permeation profile and anti-inflammatory effect of anemonin extracted from weilingxian. AB - The aim of this study was to evaluate the skin permeability of anemonin, which was extracted from the Chinese herb weilingxian, and its potency of relieving the inflammation caused by rheumatoid arthritis (RA). To optimize the formulation, the solubility of anemonin in water and selected concentration of ethanol-water vehicles was determined. The effect of ethanol on the permeation of anemonin through human skin was then studied. Additionally, the influences of hydroxypropyl methylcellulose E50 (HPMC) and Carbomer 934 in different concentrations on the permeation of drug were investigated. Finally, the anti inflammatory effect of the optimized formulation was assessed by murine model of xylene-induced ear edema. The results showed that the solubility and transdermal permeation of anemonin in ethanol-water vehicles linearly depended on the ethanol concentration. The combination of 30% ethanol and 3% Azone had a synergistic enhancement effect and was therefore selected for gel preparation. The 0.14% anemonin gel prepared with 1% HPMC exhibited the highest transdermal flux. The xylene-induced ear edema inhibitory rate of the optimized formulation was 48.85%. The results indicated that transdermal administration of anemonin is a potential modality for combating inflammation caused by RA. PMID- 27183709 TI - Caspase-3 activation in human melanoma A375 cell line by a novel selective sigma 2 agonist. AB - Two novel 8-azabicyclo[3.2.1]octan-3-ol derivatives, 11a and 11b, with high affinity for sigma-2 receptors and a very good sigma-1/sigma-2 selectivity ratio were synthesized. In comparison with several well established sigma-2 selective ligands, 11 b showed a very low sigma-1 receptor affinity. Functional assays demonstrated that 11b acts as an agonist and in A-375 human melanoma cell line is able to lower levels of procaspase-3, thus confirming a potential major role for sigma-2 pure agonists in the treatment of rapid proliferating melanoma cells. PMID- 27183708 TI - Bile acids, carriers of hepatoma-targeted drugs? AB - Previous studies display that bile acids (Bas) could be used as carriers and pharmaceutical excipients. In this study, the selective cytotoxicity of 6 bile acids (BAs) was evaluated against hepatoma cell line HepG2, human colon carcinoma cell line HT-29, gastric cancer cell line BGC823, cervical cancer cell line Hela and hepatocyte line L02. Our study suggested that most of the BAs showed cytotoxicity against a broader spectrum of tumor cells and display high cell selectivity toward HepG2. In particular, chenodeoxy- cholic acid (CDCA) exerted the most potent selective cytotoxicity against HepG2 (IC50 = 54.62 +/- 3.5 uM) and low toxicity on L02 cells (IC50 >200 uM). According to the structure-activity relationship, the position, configuration and number of OH groups in BAs could affect cell proliferation and selectivity. Moreover, the pre-mechanism of CDCA on HepG2 cells was studied by Giemsa staining, DAPI staining, AO/EB staining, apoptosis analysis and mitochondrial membrane potential assay. Results showed that CDCA could induce apoptosis and loss of mitochondrial transmembrane potential in HepG2 cells. The study inferred that CDCA might be a carrier and parent pharmaceutical excipient for hepatic carcinoma targeting drug. PMID- 27183710 TI - Effect of hypoxia on UDP-glucuronosyl transferase mRNA expression in human hepatocarcinoma functional liver celL4 cell line. AB - Although hypoxic conditions have been reported to affect the expression levels of various enzymes like cytochrome P450, the effect of hypoxia for UDP-glucuronosyl transferase (UGT) expression has been unclear. We evaluated the mRNA expression of UGTs (UGT1A1.1A6.1A9.2B7) in a functional liver cell-4 (FLC-4) cell line by three-dimensional culture under hypoxic conditions (37 degrees C, 1% O2, 5% CO2) fo 7 days. The mRNA expression of UGT1A1.1A6.1A9.2B7 decreased significantly after 3 days and that of UGT1A1.1A6.1A9 decreased significantly after 7 days. Hypoxic conditions affect the expression levels of UGT enzymes, thus the adjustment of dosage and interval should be considered in drug therapy that metabolized by UGT. PMID- 27183711 TI - Oxymatrine mediates Bax and Bcl-2 expression in human breast cancer MCF-7 cells. AB - The aim of this study was to explore the effects of oxymatrine in treating breast cancer patients using biomolecular methodology. Human breast cancer MCF-7 cells were treated with oxymatrine at concentrations of 0 (control), 25, 50 and 100 ug/mL. Apoptosis assay by Annexin/PI staining was performed to examine the effects of oxymatrine on apoptotic rates of MCF-7 cells at time points of 24 h, 48 h, and 72 h after treatment. Real-time PCR was performed for the mRNA abundance of Bax and Bcl-2 after the cells were treated with oxymatrine at concentration of 0, 25, 50, and 100 ug/mL at the time points of 24, 48, and 72 h. Western blotting was performed when the cells were treated with oxymatrine at various concentrations for 72h. High concentration of oxymatrine at 100 ug/mL enhanced apoptosis by 6.4-fold at 72 h compared with control (33.16% vs. 4.47%; t= 9.82, p< 0.001). Oxymatrine at 100 ug/mL up regulated Bax mRNA abundance by 169 % at 72 h (t = 18.32, p = 0.001), and reduced Bcl-2 mRNA abundance by 24 % at 72 h (t = 6.30, p = 0.001) compared with control. Oxymatrine enhanced the expression of Bax protein while reduced the expression of Bcl-2 protein. Oxymatrine treatment showed pro-apoptotic effects in breast cancer MCF-7 cells, and these effects correlated with the up regulation of Bax transcription and protein expression and the down regulation of Bcl-2 transcription and protein expression in a time- and dose-dependent manner. CONCLUSION: Oxymatrine had effects in promoting apoptosis in human breast cancer MCF-7 cells by mediating the mRNA and protein expression levels of Bax and Bcl-2. PMID- 27183712 TI - Ivy leaves dry extract EA 575(r) decreases LPS-induced IL-6 release from murine macrophages. AB - IL-6 plays a key role in the course of inflammatory processes as well as in the regulation of immune responses by the release of different cytokines. IL-6 is produced e.g. by macrophages recruited to the airways in response to a variety of inflammatory stimuli like allergens and respiratory viruses. Patients with inflammatory airway diseases therefore may benefit from therapies targeting the IL-6 pathway, e.g. reduction of the IL-6 release. Within this context, we tested the influence of the ivy leaves dry extract EA 575(r) on the LPS-induced release of IL-6 from murine macrophages (J774.2). One point seven ug/ml (5 uM) corticosterone served as positive control and was able to reduce LPS-induced IL-6 release by 46 +/- 4%. EA 575(r) was tested in concentrations between 40 and 400 ug/ml. EA 575(r) decreased the LPS-induced IL-6 release in a dose-dependent manner and statistically significant by 25 +/- 4%, 32 +/- 4%, and 40 +/- 7% in concentrations of 80, 160, and 400 ug/ml, respectively. The present data suggest an anti-inflammatory effect of EA 575(r) used in therapy of chronic- and acute inflammatory airway diseases accompanied with cough. PMID- 27183714 TI - [MOLECULAR ASPECTS OF BRUCELLA PERSISTENCE]. AB - Brucellosis is a dangerous zoonotic disease of animals and humans caused by bacteria of the genus Brucella, which are able to survive, multiply, and persist in host cells. The review is devoted to the Brucella species persistence connected to the molecular mechanisms of escape from innate and adaptive immunity of the host and active interaction of effector proteins of the type IV secretion system with the host's signaling pathways. Understanding of the molecular mechanisms used by Brucella for the intracellular persistence in the host organism can allow us to develop new and effective means for the prevention and treatment of chronic brucellosis infection. PMID- 27183713 TI - Phenolic profiling of an extract from Eugenia jambos L. (Alston)--the structure of three flavonoid glycosides--antioxidant and cytotoxic activities. AB - Phenolic metabolite profiling and identification using high performance liquid chromatography (HPLC) coupled to high resolution accurate mass spectrometry (HR ESI-MS) with detection of negative ions was used for assaying the complex mixture of phenolics of an aqueous ethanol leaf extract of Eugeniajambos L. (Myrtaceae). Eight known polyphenolics were tentatively identified, and, in addition, three hitherto unknown flavonol-O-glycosides were detected in the extract. These unknowns were taken as the targets and isolated by means of consecutive polyamide S6, MCI gel and repeated Sephadex LH-20 column fractionation. The isolation and purification were monitored by HPLC/ESI-MS. The isolates were subsequently identified as quercetin 3-O-xylosyl-(1"' --> 2")-O-xyloside, myricetin 7 methylether 3-O-xylosyl-(1"' --> 2")-rhamnoside and myricetin 3',5'-dimethyl ether 3-O-xylosyl-(1"'-->* 2")-O-rhamnoside. All known metabolites were also separated by applying the same chromatographic techniques. ESI-MS, 1H and 13C NMR spectra were then recorded, completely interpreted and confirmed by HR-ESI-MS and 2D NMR spectroscopy. In order to get information about biological activities of E. jambos the extract was tested for radical scavenging activity by DPPH and ORAC assay. In addition, its cytotoxicity was assessed by the neutral red assay against non-tumorigenic HaCaT keratinocytes and the human bladder carcinoma cell line 5637. PMID- 27183715 TI - [STRUCTURE AND DISTRIBUTION OF THE RETROTRANSPOSON BOV-B LINE]. AB - The classification of mobile elements was discussed. Special attention was devoted to the retroelement of the LINE group: retrotransposon Bov-B LINE. The history of its origin and distribution in the nature was considered. The results of the phenomenon of horizontal transition of the retrotransposon Bov-B LINE between evolutionally distant classes were discussed. PMID- 27183717 TI - [ABILITY OF STAPHYLOCOCCUS OF VARIOUS STRAINS TO CREATE BIOFILMS AND THEIR EFFECT ON HUMAN BODY CELLS]. AB - The urgency of the staphylococcus research is due to its ability to cause severe infections: softtissue infections, endocarditis, sepsis, toxic shock syndrome, and food poisoning. Coagulase-positive Staphylococcus aureus is the main infection agent of intrahospital infections. This agent has many factors of pathogenicity, which are well known. Among the coagulase-negative staphylococcus (CNS) strains, S. haemolyticus and S. epidermidis are clinically important, because they cause infections in patients with weak immune system. The mechanisms of the CNS pathogenicity are insufficiently understood. The goal of this work was to evaluate the potential pathogenicity of clinical strains of CNS from their capacity to create biofilms and the character of their interaction with human body cells by the example of the HT-29 cell culture. The research was carried out in laboratory strain S. aureus ATCC 29213 and clinical strains S. haemolyticus SH39, S. epidermidis SE36-1 isolated from the neonatal autopsy materials. The visual tests of biofilm formation by each strain and testing of the impact of the strains on the cell culture HT-29 was carried out in this work. The two species of CNS form biofilms at a higher rate than S. aureus. Upon incubation for 2 h of HT-29 cells with staphylococcus strains tested in this work, adhesion of bacteria on cell surface was observed. The adhesion was most pronounced in case of S. aureus ATCC 29213 and S. haemolyticus SH39. Upon 3 h of incubation with S. aureus ATCC 29213 and S. haemolyticus SH39, destruction of cell HT-29 monolayer was observed. The incubation for 24 h with the 3 strains tested in this work caused complete destruction of cell HT-29 monolayer. The maximal toxic effect on HT-29 cells was inherent in the strain S. haemolyticus SH39. The aggregate of the results obtained in this work indicates the presence of the pathogenicity factors in the strains S. haemolyticus SH39, which require additional research. PMID- 27183716 TI - [MOLECULAR-GENETIC ANALYSIS OF MICROORGANISMS WITH INTRAEPITHELIAL INVASION ISOLATED FROM PATIENTS WITH COLORECTAL CANCER]. AB - The facultative aerobic bacteria isolated from the mucosa of rectum in patients with colorectal cancer in the zone of malignant tumor and neighboring normal mucosa was studied using molecular-genetic methods. The species attribution of bacteria was implemented using the cultural-morphological analysis and sequencing of the 16S rRNA locus. The microorganisms with the intraepithelial invasion to rectal mucosa isolated were identified as representatives of the adherent invasive (AIEC) subgroup of Escherichia coli and species Klebsiella pneumonia. The molecular analysis by genetic determinants controlling adhesive, hemolytic, and toxigenic activity revealed that some bacterial isolates were able to produce toxins with potential cancerogenic activity (e.g., colibactin and cytotoxic necrotic factor I). Certain bacterial species isolated from malignant and normal rectum epithelium of the same patient demonstrated no difference between analyzed factors of toxigenicity. PMID- 27183718 TI - [USE OF THE REAL-TIME PCR FOR STUDY OF THE PERIODONTAL MICROBIOME IN PATIENTS WITH COMBINED PATHOLOGY OF GASTRODUODENAL ZONE AND CHRONIC PERIODONTITIS]. AB - The total of 54 patients with chronic periodontitis of different severity was tested using real-time PCR (Dentoflor kit). The group included 38 patients with chronic gastritis. For the first time, a higher prevalence of Treponema denticola in periodontium of males in comparison with females was demonstrated. The patients with chronic gastritis had more human genome DNA at their periodontium than healthy individuals. Non-parametric statistical analysis demonstrated high association of periodontium colonization with. T. forsythensis and T. denticola (but not Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia) with the severity of the chronic periodontitis. PMID- 27183720 TI - [GENOTYPING OF THE BURKHOLDERIA MALLEI STRAINS BASED ON DIFFERENT REGION ANALYSIS]. AB - Development of the genotyping methods of glanders agent is urgent due to its high pathogenicity, lack of effective preventive measures and threat of the use of Burkholderia mallei as a biological weapon. In this work we proposed a scheme for the typing of the B. mallei strains based on different region analysis (DFR). The choice of variable loci differentially presented in various strains of glanders agents was performed by analyzing annotated whole-genome sequences of the B. mallei strains. Primers and fluorescence probes were designed for 9 selected loci. The amplification conditions for different regions were optimized in two variants: with electrophoretic detection and hybridization-fluorescence detection in the strip format. The possibility of applying the DFR analysis to genetic characterization of strains was assessed in 14 B. mallei strains. The genetic profiles of the studied B. mallei strains revealed that the developed DFR-typing scheme was characterized by high discrimination power (Hunter-Gaston index value was 0.92), reproducibility, rapidity, easy interpretation, and applicability for epidemiological surveillance of glanders. PMID- 27183719 TI - [MOLECULAR CHARACTERISTICS OF THE MULTIDRUG-RESISTANT MYCOBACTERIUM TUBERCULOSIS STRAINS IN THE NORTHWEST RUSSIA]. AB - The goal of this work was to study the genotypic characteristics of the multidrug resistant (MDR, i.e., resistant to at least rifampicine and isoniazid) Mycobacterium tuberculosis strains isolated in 2011-2012 from tuberculosis (TB) patients in the Northwest Russia. Spoligotyping of 195 M. tuberculosis isolates identified 14 different spoligotypes and assigned isolates to the genetic families Beijing (n = 162, 83%), LAM (n = 15), H3/URAL (n = 14), as well as T, Haarlem and X. Spoligotypes SIT1 (Beijing), SIT42 (LAM) and SIT262 (H3/URAL) were the most prevalent. Irrespective to the genotype, all the isolates were resistant to streptomycin. The multidrug resistance was accompanied by the resistance to ethionamide (56%), amikacin (31%), kanamycin (40%), and capreomycin (33%). The ethambutol resistance was found in 71% (n = 115) and 42% (n = 14) of the Beijing and non-Beijing strains, respectively (p < 0.05). In conclusion, the multidrug resistant M. tuberculosis population circulating in the Northwest Russia continues to be dominated by the Beijing family strains. PMID- 27183721 TI - [COMPARATIVE ANALYSIS OF THE MLVA25- AND MLVA7-TYPING ACCORDING TO THEIR ABILITY TO ASCERTAIN FOCAL AFFILIATION OF YERSINIA PESTIS STRAINS BY THE EXAMPLE OF ISOLATES FROM THE CENTRAL-CAUCASIAN HIGHLAND NATURAL PLAGUE FOCUS]. AB - Comparative analysis of the MLVA25- and MLVA7-typing ability to evaluate focal belonging of Y. pestis strains by the example of bv. medievalis isolates from the Central-Caucasian highland natural plague focus was carried out. The MLVA25-types of-82 isolates from this area were determined and included into the database containing information on 949 Y. pestis strains from other natural foci of Russia and other countries. Categorical-UPGMA dendrograms were created on the bases of the data concerning all 25 VNTR loci or only seven of them, which were recommended by the experts of the Russian Research Anti-Plague Institute "Microbe" for differentiation of the Y. pestis strains according to their affiliation to specific foci. The obtained data indicated greater possibility of diagnostic mistakes in the case of the MLVA7-typing and supported expediency of division of the Central-Caucasian highland natural plague focus into two sub foci. PMID- 27183722 TI - [THE ETIOLOGY AND PATHOGENESIS OF SUCCESSIVE MAKING TEST ON HYPERTRIGLYCERIDEMIA, HYPERCHOLESTEROLEMIIA AND HYPOGLYCEMIA. THE COMMON CHARACTER OF ETIOLOGIC FACTORS OF METABOLIC PANDEMIC AND COMPENSATORY ROLE OF APOC-111]. AB - The concepts of atherosclerosis as afatly acids pathology, deficiency syndrome in cells ofpolyene fatty acids were expounded in 1990. The spirits cholesterol and glycerin play integrated physical chemical function in fatly acids' metabolism in transforming polar fatty acids into such non-polar form as ethers cholesterol and triglycerides. The amount of fatty acids transferred by lipoproteins to triglycerides significantly exceeds amount of fatty acids as ethers cholesterol. The triglycerides dominate in cells and ethers cholesterol outside cells. The hypertriglyceridemia is a disorder of transformation in blood of phylogenetically late insulin-dependent palmitic and oleinic lipoproteins of very low density and receptor apoE/B-100-endocytosis by cells of non-ligand lipoproteins of very low density. The hypertriglyceridemia is a disorder of support of cells with energy substrates, problem of cell "energetics", formalton of adenosine triphosphate. It is proposed to evaluate prognostic value of spirits cholesterol in blood plasma only in case of physiological level of triglycerides. The spirits cholesterol never exceeds content of triglycerides however high would be content of spirits cholesterol in blood plasma under family hypercholesterolemia. The increasing of concentration of triglycerides always results in increasing of content of spirits cholesterol and especially spirits cholesterol-lipoprotein of low density. If level of triglycerides and spirits cholesterol is increased normalization of content of triglycerides using diet is to be implemented To evaluate content of spirits cholesterol in blood plasma is rational only under physiological level of triglycerides. Quite often, after decreasing of content of triglycerides content of spirits cholesterol spontaneously decreases by itself. It is supposed that functions of phylogenetic early resident macrophages of intima and late monocytes macrophages differs. The functional characteristics of second ones under surplus induction by substrate (non-ligand lipoproteins) forms atheromatosis. The increasing of content of apoC-III in blood plasma--test of accumulation of blood of a physiologicpal mitic lipoproteins of low density, compensatory activation of lipolysis of triglycerides in lipoproteins of low density, but not blockade of biological function of trophology, biological reaction of exotrophy. PMID- 27183723 TI - [THE LONG NON-CODING RNA ASSOCIATED WITH CANCEROGENESIS: BIOLOGICAL SIGNIFICANCE AND PERSPECTIVES OF APPLICATION IN DIAGNOSTIC]. AB - The last decade is characterized by development of such technologies as RNA sequencing and biochips which resulted in discovery of new perspective biomarkersfor personalized diagnostic of cancer. Among them, the long non-coding RNA (IncRNA) are of special interest because according the recent studies they are positioned as important regulators of gene expression on epigenetic, transcription and post-transcription levels. The review considers the role of long non-coding RNA in cancerogenesis. The corresponding of their application in diagnostic is evaluated. A number of examples ofperspective diagnostic and prognostic markers. Their degree of implementation in oncological practice is discussed. PMID- 27183724 TI - [THE CONTENT OF ELECTROLYTES IN DIFFERENT BIOLOGICAL MEDIUMS UNDER ACUTE CORONARY SYNDROME]. AB - The sampling of study included 172 patients with ischemic heart disease: 146 with acute coronary syndrome, including myocardial infarction (88 patients) and unstable stenocardia (58 patients); 26 patients with stable stenocardia functional class II-III. At the 1-3 day of hospitalization blood was taken of cubital vein. The mixed unstimulated saliva was selected. In both of them conte of calcium, sodium and potassium was tested (mmol/l). Under acute coronary syndrome, in blood content of calcium was 2. sodium--139.6 and potassium--4.5 i.e. the content was lower than in case of stable stenocardia (2.4; 139.8; 4.7 correspondingl In saliva under acute coronary syndrome higher content of calcium (1.05) and potassium (34.66) and lower content of sodiu (25.42) was established in comparison with stable stenocardia (0.81; 33.7; 28.08 correspondingly). The distribution coefficien (blood/saliva) of calcium, sodium and potassium were higher under myocardium infarction than under unstable stenocardia at uncomplicated course of acute coronary syndrome. PMID- 27183725 TI - [THE BIOCHEMICAL AND PATHOPHYSIOLOGICAL MARKERS OF CHEMICAL EFFECT ON ORGANISM, THEIR INFORMATIVENESS AND DIAGNOSTIC SIGNIFICANCE]. AB - The sampling of study included 185 examined workers. Out of them 90 work at "Opitnii zavod Neftekhim" (67 females and 23 males) and 95--at "Kaustik" (64 females and 31 males) from various workshops of the given enterprises. To determine biochemical indicators samples of blood, saliva and urine were collected. The study was carried out in concordance with ethic principles of the Helsinki world medical association declaration, 2008 ed. with receiving written consent of patient to participate in study. PMID- 27183726 TI - [THE TECHNIQUE OF HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY FOR SIMULTANEOUS DIAGNOSTIC OF INHERENT HYPERPLASIA OF ADRENAL GLANDS TYPE I AND II]. AB - The article considers the technique of high-performance liquid chromatography making it possible simultaneously detect cortisol, cortisone and secondary steroids in serum for consequent analysis of common reversed-phase high performance liquid chromatography with ultraviolet under 240 nm. The liquid liquid extraction from alkaline medium in diethyl ether The separation using column of 150x4.6 size ODS 3.5 mkm in isocratic mode. The eluent acetonitrile- 0.02 M phosphate buffer pH 8.0--isopropanol (40:60:1). The application of proposed technique managed to separate cortisol, cortisone, dexamethasone, corticosterone, 11-desoxicortisol, testosterone, desoxicorticosterone, 17alpha gidroxiprogesterone and androstendion in 20 minutes. The simplicity, reproducibility and sufficient selectivity and sensitivity of technique permit implement it in clinical practice for simultaneous diagnostic of inherent hyperplasia of adrenal glands type I and II. PMID- 27183727 TI - [THE OPTIMIZATION OF NUTRITION FUNCTION UNDER SYNDROME OF RESISTANCE TO INSULIN, DISORDER OF FATTY ACIDS' METABOLISM AND ABSORPTION OF GLUCOSE BY CELLS (A LECTURE)]. AB - The phylogenetic processes continue to proceed in Homo Sapiens. At the very early stages ofphylogenesis, the ancient Archaea that formed mitochondria under symbiotic interaction with later bacterial cells conjointly formed yet another system. In this system, there are no cells' absorption of glucose if it is possible to absorb fatty acids from intercellular medium in the form of unesterfied fatty acids or ketonic bodies--metabolites of fatty acids. This is caused by objectively existed conditions and subsequent availability of substrates at the stages ofphylogenesis: acetate, ketonic bodies, fatty acids and only later glucose. The phylogenetically late insulin used after billions years the same dependencies at formation of regulation ofmetabolism offatty acids and cells' absorption of glucose. In order that syndrome ofresistance ceased to exist as afoundation of metabolic pandemic Homo Sapiens has to understand the following. After successful function ofArchaea+bacterial cells and considered by biology action of insulin for the third time in phylogenesis and using biological function of intelligence the content ofphylogenetically earlier palmitic saturated fatty acid infood can't to exceed possibilities of phylogenetically late lipoproteins to transfer it in intercellular medium and blood and cells to absorb it. It is supposed that at early stages of phylogenesis biological function of intelligence is primarily formed to bring into line "unconformities" of regulation of metabolism against the background of seeming relative biological "perfection". These unconformities were subsequently and separately formed at the level of cells in paracrin regulated cenosises of cells and organs and at the level of organism. The prevention of resistance to insulin basically requires biological function of intelligence, principle of self-restraint, bringing into line multiple desires of Homo Sapiens with much less extensive biological possibilities. The "unconformities" of regulation of metabolism in vivo are etiological factors of all metabolic pandemics including atherosclerosis, metabolic arterial hypertension, obesity and metabolic syndrome Tertiannondatum. PMID- 27183728 TI - [THE VERIFICATION OF ANALYTICAL CHARACTERISTICS OF THREE MODELS OF GLUCOMETERS]. AB - The individual portable systems of control of glucose level in blood commonly known as glucometers permit to patients with diabetes mellitus to independently correct pharmaceutical therapy. The effectiveness of this correction depends on accuracy of control of glucose level. The evaluation was implemented concerning minimal admissible accuracy and clinical accuracy of control of glucose level of devices Contour TC, Satellite Express and One Touch Select according standards expounded in GOST 15197-2011 and international standard ISO 15197-2013. It is demonstrated that Contour TC and One Touch Select meet the requirements of these standards in part of accuracy while Satellite Express does not. PMID- 27183729 TI - [THE REFERENCE VALUES OF AGGREGATION OF PLATELETS IN ADULT POPULATION OF THE ASTRAKHAN OBLAST USING AGGREGOMETER MULTIPLATE]. AB - The modern international standards recommend each laboratory to develop or to confirm available in literature the reference intervalsfor every laboratory indicator In the Astrakhanskaia oblast, sampling of128 healthy males andfemales were examinedfor aggregation function of thrombocytes using impedance technique and applying aggregometer Multiplate ("Verum Diagnostica", Germany). The study used as inductors peptide activating receptor of thrombin; arachidonic and adenosine diphosphoric acids. The reference range of aggregation of thrombocytes with peptide activating receptor of thrombin, at aggregometer Multiplate, in healthy population of theAstrakhanskaia oblast made up to 815.2-1498.4 AU/min, with arachidonic acid--660-1341 AU/min. with adenosine diphosphoric acid--598 1120 AU/min. PMID- 27183730 TI - [ON DEVELOPMENT OF TOOLS OF IMMUNE DIAGNOSTIC OF INFECTIOUS DISEASES: PROBLEMS OF DIAGNOSTIC IN VIVO AND IN VITRO]. AB - The article considers a number of problematic issues concerning development of effective means of immune diagnostic of infectious diseases of bacterial and mycotic etiology related to approaches of choosing appropriate diagnostic targets. PMID- 27183732 TI - [THE MOLECULAR TECHNIQUES OF DIAGNOSTIC OF GINGIVITIS AND PERIODONTITIS IN HIV INFECTED PATIENTS]. AB - The examination was carried out in the Moscow clinical infectious hospital No 2 concerning 102 patients with verified diagnosis "AIDS-infection" and seropositive according results of detection of anti-HIV-antibodies in blood serum. The study was organized to analyze rate ofcolonization of gums with virulent anaerobic bacteria in HIV-infected (polymerase chain reaction) and antibodies to HIV in gingival fluid (enzyme-linked immunosorbent assay). It is established that in HIV infected patients, in scrape from gingival sulcus dominate anaerobic bacteria P. gigngivalis and A. ctinomycetemcomitans and in case of periodontitis--P. gingivalis and T. forsythia. The received data permits recommending the test system "Multident-5" for polymerase chain reaction diagnostic. The reagents kit "Calypte(r)HIV-1/2"--for enzyme-linked immunosorbent assay gingival fluid. The results of polymerase chain reaction and enzyme-linked immunosorbent assay have no impact of concomitant stomatological (periodontitis, gingivitis) and somatic pathology. PMID- 27183731 TI - [THE FORMATION OF BIOFILM IN OPPORTUNISTIC MICROORGANISMS IN BLOOD PLASMA DEPENDING ON CONTENT OF IRON]. AB - The article considers results of analysis offormation of biofilm of priority opportunistic pathogens in blood plasma and LB-broth. As compared with LB-broth, bloodplasma stimulates formation of biofilm of microorganisms in the following sequence: Staphylococcus aureus > Pseudomonas aeruginosa > Escherichia coli. The application oftechnique of infra-redspectroscopy of bio-films established that blood plasma promotes formation of external exopolysaccharides of S.aureus. The cultivation of bio-films in plasma depending on content of iron demonstrated that the analyzed strains of S. aureus, P. aeruginosa, E. coli form bio-films in a better way in plasma with normal content of iron and iron-deficient and iron loaded plasma decreases their activity of formation of biofilm. PMID- 27183733 TI - [TMOSKOVHE COMPARATIVE CHARACTERISTIC OF GROWTH MEDIUMS FOR SEPARATION OF CORYNEBACTERIA]. AB - The comparative tests of growth mediums for isolation and accumulation of diphtheria bacteria were implemented. The testing consisted of six series of growth medium "Corynebacagar" produced by the state research center of applied microbiology and biotechnology and three series of blood tellurite agar. The concluding results of identification of biological indicators of all series of growth nutrient mediums are presented The "Corynebacagar" is recommended for application in health care practice for primary inoculation of pathological material during implementation of cultural analysis on diphtheria. PMID- 27183734 TI - The Politically Active Nurse. PMID- 27183736 TI - I Just Couldn't Leave. PMID- 27183735 TI - Summary of Code of Ethics. AB - The Guide to the Code of Ethics for Nurses is an excellent guideline for all nurses regardless of their area of practice. I greatly enjoyed reading the revisions in place within the 2015 edition and refreshing my nursing conscience. I plan to always keep my Guide to the Code of Ethics for Nurses near in order to keep my moral compass from veering off the path of quality care. PMID- 27183737 TI - Keep Your Distance! Preventing Distractions to Reduce Medication Errors. PMID- 27183738 TI - Unequal Access: African Immigrants and American Health Care. PMID- 27183740 TI - Government announces one per cent pay increase for public sector staff. PMID- 27183739 TI - Limited English Proficiency: Impact on Health Literacy and Health Disparity. PMID- 27183741 TI - Information sharing app aims to address families' 'biggest fears' about home care. PMID- 27183742 TI - Cutting the complexity of a topical treatment-reducing regimen for atopic eczema. PMID- 27183744 TI - Reflections on a #DayWithDave. PMID- 27183743 TI - Jean Robinson responds. PMID- 27183746 TI - Mobile devices as 'calming tools' for children. PMID- 27183747 TI - Study links asthma with fertility. PMID- 27183748 TI - Seeing the signs. AB - Invasive meningococcal disease, causing meningitis and/or septicaemia, can kill within hours and leave a significant number of survivors with lifelong disability. Even though there are now three meningococcal vaccines in the U.K. routine immunisation schedule, not all cases will be prevented. There are also other bacterial, viral and fungal causes of meningitis that are not prevented by vaccines, it is too early to assess the impact of recent changes to the schedule and it is vital that everyone is aware of the signs and symptoms, and remains vigilant. PMID- 27183749 TI - Childhood epilepsy: a clinical update. PMID- 27183750 TI - Performing school nursing: Narratives of providing support to children and young people. AB - Child and adolescent mental health is an important public health issue within the U.K. Providing support to young people to help them cope with everyday life is a key aspect of the school nurse's role. Yet there is a paucity of published research within the U.K. and internationally about how this support is provided. Using a narrative inquiry approach this study set out to address the following research question, 'How do school nurses provide support to young people?' Stories were gathered from 11 school nurses identified through purposive sampling to explore their experiences of providing support to young people. Poetic representations were used to tell the stories of individual school nurses; an approach seen to be innovative within school nursing research. Spatiality theory was used as a framework to explore different spaces used when providing support to young people. This study extends the current school nursing literature about what it means to provide support. The importance of regular support and building trusting relationships is identified Yet challenges exist in terms of the amount of emotional investment required by the nurses, as well as a lack of workforce capacity and organisational demands. PMID- 27183752 TI - Best practice at the new birth review? AB - This paper aims to discuss the infant assessment component of the new birth review. The Healthy Child Programme (HCP) is the guidance that underpins the practice of health visiting at this contact. It should be clearly stated that this article is not referring to the Newborn and Infant Physical Examinations (NIPE) undertaken by medical practitioners and midwives at birth and by GPs at six weeks respectively. From reviewing other provider organisations' health visiting standards online, through discussions at professional. health visiting forums such as The National Professional Advisory Group and from the authors small qualitative study as part of a master's dissertation there appears to be a wide variation in health visiting practice. There are health visiting (HV) services that offer a universal infant assessment, while other HV services assess the infant in other ways at the request of the parent. However, some services do not undertake an infant assessment at all. The Health Visiting Core Specification states that the health visitor should be able to assess the baby's growth and be able to conduct an ongoing review. This paper discusses the historical background that underpins the different approaches and discusses the implications for different practice at a universal healthy child programme contact. The author discusses tools that evidence PMID- 27183751 TI - Something fishy about home-cooked infant feeding recipes. AB - There is no evidence available indicating whether popular infant and young child feeding (IYCF) cookbooks provide nutritious options for home-cooking, what the most common food types are within the recipes, and what accompanying dietary advice is provided to parents. This study surveyed available IYCF cookbooks from local libraries and Amazon UK's top 20 bestsellers (May to July 2013 to examine the prevalence and nutritional content of cookbook recipes comparing these to recommendations whilst investigating the messages portrayed towards parents on giving different foods to their child during IYCF. Vegetable-based recipes (median=29) predominated main-meal options while a proportional number of red meat, poultry and seafood-based recipes were included providing parents with options of protein-rich recipes for their young child. These home-cooked recipes adequately met or exceeded age-specific dietary recommendations. Mixed messages were apparent on the inclusion of foods during IYCF within and across these cookbooks, in particular for seafood, highlighting a lack of consistent advice portrayed to parents during the early years. Community-based health professionals should advise parents of the inconsistent and incorrect messages on food inclusion portrayed in some IYCF cookbooks and guide them towards formal recommendations. PMID- 27183754 TI - Bringing Hope. PMID- 27183753 TI - Last word with...Carol Long. PMID- 27183755 TI - 'Negotiating' drug prices for Medicare. PMID- 27183757 TI - Promoting value through antimicrobial stewardship. AB - An institution that uses a value-based approach to manage and prevent problems related to the suboptimal use of antibiotics will improve its bottom line through: Efficiencies brought about by aggressive management of institutional resources. Reductions in hospital admission/readmission. Fewer complications. Better transitions in care. Increased revenues through preferential referrals. PMID- 27183756 TI - Healthcare not-for-profits: FASB exposure draft highlights flexibility in financial statement presentation. AB - A new version of the FASB accounting standard covering not-for-profit healthcare organizations contains potentially significant changes to the statement of operations and changes in net assets, statement of cash flows, and notes to the financial statements. Healthcare organizations already have tremendous flexibility with disclosures around all aspects of their business. Although auditors prefer to see only information that can be effectively audited, this preference does not prevent organizations from expanding on certain activities or transactions covered by GAAP in their footnotes. PMID- 27183758 TI - Orchestrating ACO success: how top performers achieve shared savings. AB - Leaders of the top-performing accountable care organizations in the Medicare Shared Savings Program attribute the success of their organizations in large part to seven strategies: Seek action-oriented leadership. Transform primary care physician practices. Keep patients out of the emergency department. Ensure all transitions are smooth. Make effective use of available data. Share information on physician performance. Keep patients engaged. PMID- 27183759 TI - Value-based physician compensation: a link to performance improvement. AB - To prepare for the healthcare industry's transition to value-based care, Mayo Clinic Health System implemented a new, value-focused physician compensation plan as part of a larger initiative aimed at systemwide clinical integration. The plan uses three value-based metrics, focusing on outcomes, safety, and patient experience, that initially would determine 5 percent of a physician's compensation. Notable improvements achieved in the first year of the plan's implementation were strong indicators of the potential effectiveness of such a plan. PMID- 27183760 TI - The value of employees in a value-based care system. AB - To be successful under value-based payment, hospitals will require a healthy communication culture in which workers in the trenches are committed, engaged, and focused. In such a culture, employees should feel free to express their fears and doubts, accept and apply constructive feedback, and participate creatively. Mistakes should be seen not as cause for disciplinary action but as learning opportunities. New hires should have a willingness to continually learn and work independently, be unafraid of making mistakes, and be committed to adding value through the delivery of improved care and enhanced outcomes. PMID- 27183761 TI - Maintaining qualification for 340B. AB - After initial acceptance in the 340B Drug Pricing Program, hospitals and health systems should monitor and take steps to maintain their disproportionate share hospital status to continue to qualify for participation. Proactively managing the Supplemental Security Income (SSI) Ratio will ensure the organization avoids an unexpected decline in the Medicare portion of its 340B patient base. Even with the surge resulting from Medicaid expansion, tracking patient eligibility for Medicare/ SSI to ensure all patients who qualify are appropriately enrolled in the program is an important step in maintaining 340B program eligibility. PMID- 27183762 TI - Building a value-based primary care network for population health. AB - The move to value-based care has many primary care physicians worried about the future of their practices. Six strategies developed by a clinic in Northeastern Oklahoma can help: Determine your "why." Let leadership drive. Educate staff, and communicate the transformation plan. Find alignments. Get patients engaged. Scale the program with technology. PMID- 27183763 TI - High deductibles, high value? PMID- 27183764 TI - CMS data reveal cost increases for Medicare patients. PMID- 27183765 TI - Ibrutinib (Imbruvica). Relapsed chronic lymphocytic leukaemia and mantle cell lymphoma: uncertain impact on survival. AB - codynamic interactions are also likely in view of its adverse effect profile. There is no consensus on the treatment of patients with refractory or relapsed mantle cell lymphoma, or for patients with relapsed or possibly refractory chronic lymphocytic leukaemia. Ibrutinib inhibits an enzyme involved in regulating B lymphocyte activity. It has been authorised in the European Union for these conditions. Clinical evaluation of ibrutinib in mantle cell lymphoma is based on a single non-comparative trial in 111 patients, in which the median overall survival time was 22.5 months. Clinical evaluation of ibrutinib in chronic lymphocytic leukaemia is based on two randomised trials. One unblinded trial compared ibrutinib versus ofatumumab and involved 391 patients, most of whom were sufficiently fit to receive anticancer combination therapy. Ibrutinib was more effective than ofatumumab, but the choice of this comparator might not have been appropriate for most of the patients who received it. The other double blind, placebo-controlled trial involved 578 patients with relapsed or refractory chronic lymphocytic leukaemia. Ibrutinib was added to the bendamustine + rituximab combination. No significant difference in mortality was observed between the two groups. The main adverse effects of ibrutinib were: gastrointestinal disorders such as diarrhoea; life-threatening infections and bleeding disorders; and cardiac disorders, including atrial fibrillation. Ibrutinib carries a risk of multiple pharmacokinetic interactions. Pharmacodynamic interactions are also likely in view of its adverse effect profile. PMID- 27183766 TI - Advanced Directives and Advanced Care Planning for Healthcare Professionals. AB - The purposes of this study were to assess healthcare professionals' need for information on advanced directives and to implement and evaluate an educational plan for change in knowledge and behaviors related to advanced directives. End-of life (EOL) care is an important topic for patients to discuss with their families and healthcare professionals (HP). Needs assessment data were collected from healthcare providers at an urban trauma intensive care unit (ICU) in Louisville, Kentucky on concepts related to end-of-life. Next, healthcare professionals participated in an educational intervention focused on: knowledge about advanced directives; communication techniques for healthcare professionals to use with patients and their families; awareness of the patient's level of illness in advanced care planning; and specifics about living wills in Kentucky and how to complete one. Pre- and post-test data were collected to evaluate change in knowledge, capability an average of 8.7 years (SD = 9.1; range = 1.9-35 years) in healthcare and worked an average of 8.4 years (SD = 9.3; range = 4 months to 35 years) in their respective ICUs. Eighty-seven percent did not have an AD in place even though their perceived knowledge about AD remained moderate throughout pre- and post-test scores (3.3 to 3.8 on a 5 point scale, respectively). Total post test scores revealed a 2% improvement in correct responses. These findings point to the need for education of healthcare providers in the ICU to increase early AD and ACP discussions with patients and their families. PMID- 27183767 TI - Staff Development and Simulation. PMID- 27183768 TI - Taking Health Promotion to the Louisville Community. PMID- 27183769 TI - Shaken but not broken: Supporting breastfeeding women after the 2011 Christchurch New Zealand earthquake. AB - The 2011 Christchurch New Zealand earthquake adversely affected large numbers of people and resulted in many mothers and infants evacuating the city. In the town of Timaru, an emergency day-stay breastfeeding service assisted evacuee women. The service was established after media messaging alerted mothers to the importance of breastfeeding and the location of breastfeeding assistance. The local hospital provided rooms for the breastfeeding support service, which delivered counselling to mothers experiencing breastfeeding challenges. The vulnerability of infants in emergencies demands that governments and aid organisations plan to support their wellbeing and access to safe food and liquid. Plans should be developed in accordance with the Emergency Nutrition Network's Operationalguidance on infant and young child feeding in emergencies and include breastfed and formula-fed infants. Many countries have existing health resources and personnel with the expertise to support infant feeding in emergencies. However, only comprehensive pre-emergency planning can ensure that infants are protected. PMID- 27183770 TI - Women's experiences of learning to breastfeed. AB - AIM: This research explores women's experiences of learning to breastfeed. DESIGN: A purposive cohort of healthy mothers participated in individual audio recorded interviews late pregnancy and then 2 and 8 weeks after birth. All interviews were transcribed verbatim and analysed using van Manen's approach. SETTING AND PARTICIPANTS: Participants were 13 first time mothers based in a rural municipality in Victoria, Australia. KEY FINDINGS: Women's voices gave rich descriptions of their experience of learning to breastfeed. Women shared the physicality of having 'great big engorged breasts' or 'sore nipples', and 'learning to latch' while 'having so very many things happening'. CONCLUSION: Many participants felt overwhelmed with learning to breastfeed at the same time as coping with caesarean wounds, perineal trauma, uterine bleeding and extreme fatigue. FUTURE IMPLICATIONS: Parenting education needs to be offered early in pregnancy so couples can explore birthing and its potential outcomes and to introduce infant cues and behaviours as a base for understanding how these impact on breastfeeding and problem solving. PMID- 27183771 TI - Challenges in the treatment of lactational mastitis for general practitioners. AB - OBJECTIVES: To determine how GPs manage breastfeeding women with mastitis and how confident they are in treating women with breast conditions that occur during lactation. DESIGN, PARTICIPANTS AND SETTING: A cross-sectional survey conducted among all Croatian GPs. KEY FINDINGS: Sixty-four per cent of the total number of respondents (171/268) had seen a patient with lactational mastitis (LM) in the previous 12 months. Among respondents who recommended medication for the treatment of LM, 93% prescribed an antibiotic (122/131). Fifteen per cent of respondents who gave advice on infant feeding advised alternative feeding methods. Approximately half (47%) felt completely confident when treating LM while more than half (57%) felt partially confident when treating other breast conditions that can occur during lactation. CONCLUSION: The management of LM among Croatian GPs is not in full compliance with current recommendations. FUTURE IMPLICATIONS: There is a need for further training of Croatian GPs in the management of mastitis. PMID- 27183772 TI - Development of oral tolerance to allergens via breastmilk. AB - Immune responses induced in early life to environmental and dietary antigens will be decisive for children and their adult response to these antigens, and they will condition development of immune-mediated diseases such as allergies and autoimm unity Maternal influence on neonatal tolerance induction through breast feeding is probably of great importance because of dietary and environmental antigen transfer through breast milk and the pleiotropic effects of breast feeding on gut and immune system maturation. In addition, maternal history and maternal sensitization to common environmental and food antigens will probably affect antigen transfer to the breastfed child along with tolerance induction. PMID- 27183773 TI - Help patients and families as they struggle with end-of-life issues. AB - When patients appear to be reaching the end of life, case managers should find out their wishes, alert the treating physician and the rest of the staff, and ensure that patients' wishes are carried out. In an effort to encourage discussions about end-of-life care, the Centers for Medicare & Medicaid Services (CMS) has begun paying physicians for consultations on advance care planning. CMS' push toward pay for performance and bundled payments creates financial incentives for hospitals to consider alternatives to admitting patients as inpatients. Providers' feelings sometimes make them hesitant to talk about end-of life issues with patients and family members. Case managers should take a patient centered approach and find out patients' goals before bringing up hospice care, and educate family members on what to expect when they get home. PMID- 27183774 TI - Get in touch with your own feelings before talking to patients. PMID- 27183775 TI - Find out patients' goals before introducing the idea of hospice. PMID- 27183776 TI - Make sure patients, families are informed about hospice. PMID- 27183778 TI - Hospital LOS confirmed to worsen hip fracture outcomes. PMID- 27183777 TI - Swing shift case managers facilitate discharges late in the day. AB - Swing shift case managers start work at 2 p.m. at UCLA Health and facilitate discharges that need to occur late in the day. An occupancy rate that consistently is 95% or higher makes it imperative for the hospital to have good patient throughput. Day shift case managers refer cases with last minute details that could delay the discharge until the next day. The swing shift case managers cover the house and divide up the pending discharges among themselves. PMID- 27183779 TI - ED nurses ID barriers to ethical end-of-life care. PMID- 27183780 TI - [Regulation of Membrane-Dependent Reactions of Blood Coagulation]. AB - All major coagulation reactions do not occurs in blood plasma itself, these processes are actually two-dimensional reactions localized to thephospholipid membranes. Almost all blood cells, lipoproteins, and microparticles provide assembly of protein complexes. A central role among them are played by platelets and platelet-derived microparticles. On their membranes occurs the most important coagulation reactions such as activation of prothrombin by prothrombin complex, activation of factor X by complexes intrinsic and extrinsic tenase. This reactions are important for processes activation of the contact path coagulation, activation factor XI by thrombin, appearance of enzymatic activity of factor VIIa etc. This review is focused on the membrane-dependent reactions, here are discussed mechanisms and regulation these reactions and the possible prospects of the study. PMID- 27183781 TI - [Neurovisalization Studies of the Self]. AB - Paper reviews contemporary standards and results of neurovisualization studies of the human Self. It's been shown, that the medial prefrontal cortex plays the main role in supporting this mental function. The cingulate, the inferior parietal lobule and the precuneus has less influence on this process. Emotional aspects of the Self are also likely to be associated with involvement of the amygdala, and embodiment is related to the insular cortex. In schizophrenia patients, activity of identified network decreases while in case of depression, anxiety or autism it increases. PMID- 27183782 TI - [GPR119 Receptor Agonists: Characteristics, Physiological Role, Prospects of Use in the Treatment of Diabetes Mellitus Type 2 and Metabolic Syndrome]. AB - Last decade GPR119 receptor attracted great attention of many researchers groups worldwide. This receptor is expressed in enteroendocrine L- and K-intestinal cells and pancreas beta cells. First endogenous ligands for GPR119 was found in 2005: fatty acid metabolites, some phospholipids and fatty acid amides derivatives. GPR119 receptor is involved in the glucose metabolism regulation: glucose-dependent insulin secretion, glucose-independent incretin secretion, appetite control, gastric emptying, as well as beta cell proliferation. Thus, GPR119 is a "sensor" of some fatty acid derivatives and-GPR119 is a promising new pharmacological target for the treatment of type 2 diabetes. PMID- 27183783 TI - [The Role of Cytokines MIC-1/GDF15 in Development of the Old Age Disease]. AB - This review provides information about the structure and basic functions of the cytokine MIC-1/GDF15. MIC-1/GDF15 is normally contained not only in blood, but also expressed on cells of reproductive and nervous system. Its concentration increases in various diseases of the central nervous system, cardiovascular system, thromboembolism, malignant tumors and other pathological conditions, the most common in the elderly. It was demonstrated that the correlation between the level of MIC-1/GDF15 and the severity of the pathological process, disease prognosis, including fatalities, therefore it was named "predictor of death". In gene promoter MIC-1/GDF15 was detected geroprotective binding sites for peptides Lys-Glu, Lys-Glu-Asp, and Ala-Glu-Asp-Gly. Probably, these peptides regulate the synthesis of MIC-1/GDF15, whereby its geroprotective effect may be accounted. PMID- 27183784 TI - [Gas Signalling in Mammalian Cells]. AB - At the end of the last century after the discovery of signaling functions of nitric oxide (NO, II), a new class of biologically active substances was admitted. It includes so-called gas transmitters acting as intercellular and intracellular regulators of different physiological functions. Currently, this class includes such gases as NO, carbon monoxide (CO) and hydrogen sulfide (H2S). It was found that these gases regulate not only functions of the. gastrointestinal tract and the cardiovascular system, where it has been determined initially, but also affect the function of the central and peripheral nervous.systems. Apparently, they constitute a single complex of gas transmitters, which easily penetrates through the membrane and regulates numerous enzymatic and non enzymatic cells reactions. This review presents the mechanisms of gas transmitters' influence on the electrical and contractile properties of smooth muscle cells (SMC) as a possible new ways to interact with the "classical" intracellular signaling cascades (Ca2+, cyclic nucleotides) and effectors systems. On account of their interactions the role of cyclic nucleotides and calcium ions in the implementation of the signal gas molecules functions is analyzed. We summarize the literature data and the results of our own research on the role of SMC membrane ion-transporting systems in myogenic effects of NO, CO and H2S and describe possible reasons of gas transmitters multidirectional influence on the excitation-contraction coupling in SMC. PMID- 27183785 TI - [Regulation of Ovarian Function: Part of the Gas Transmitters NO, CO and H2S]. AB - This review discusses the management of ovarian function and participation in the process of a new class of cellular regulators--Gasotransmitters (NO, CO and H2S). According to modern concepts in regulatory processes, in addition to hypothalamic pituitary mechanisms involved a large and diverse group of ovary cells (interstitial, internal theca and atretic bodies, follicular epithelium, teka luteal and granulosa-luteal cells of the corpus luteum), which not only mediate the gonadotropic stimulation, but satisfy the for the production of a wide range of biologically active substances. These materials are expected to participate in all these processes gaseous mediators. However, our knowledge of topochemistry, mechanisms and the role of these substances in the important organs of the reproductive system-ovary, fragmentary and do not allow to form a holistic understanding of the cellular mechanisms by which Gasotransmitters have a regulating effect on the individual structures of the ovary in normal functioning of the body and disease. Creation of an experimental model for studying the mechanisms of gaseous mediators in different cell types of ovarian, including endothelial and smooth muscle cells of blood vessels, in which the functional significance of these substances may be particularly significant, will provide fundamental knowledge for the development of new approaches to the treatment of diseases of the reproductive system. PMID- 27183786 TI - [Biological Role of Oligomerny Matriksny of Protein of the Cartilage in Exchange Processes Connecting Tissue]. AB - In the review the literary data on studying of biological role of a oligomerny matriksny of protein of the cartilage in exchange processes connecting tissue at people and animals are provided, and also results of own researches on definition of a oligomerny matriksny of protein of the cartilage as a modern marker of a metabolism of an articulate cartilage at children from undifferentiated displaziy conjunctive tissue are briefly described. PMID- 27183787 TI - The Selection and Use of Essential Medicines. AB - This report presents the recommendations of the WHO Expert Committee responsible for updating the WHO Model Lists of Essential Medicines. It contains a summary of the Committee's considerations and justifications for additions and changes to the Model Lists, including its recommendations. Annexes to the main report include the revised version of the WHO Model List of Essential Medicines (19th edition) and the WHO Model List of Essential Medicines for Children (5th edition). In addition there is a list of all the items on the Model Lists sorted according to their Anatomical Therapeutic Chemical (ATC) classification codes. PMID- 27183788 TI - [Preimplantation Genetic Diagnosis by Blastocentesis: Problems and Perspectives]. AB - The discovery of cell-free DNA in blastocoele fluid opens new perspectives for the development of preimplantation genetic diagnosis of human chromosomal and genetic diseases. In this review we analyzed the results of the first studies, which made it possible to evaluate the effectiveness of the application of a new source of biological material and showed a high degree of agreement between the results of molecular karyotyping with cell-free DNA and blastocyst cells. The results suggest the possibility of developing a noninvasive method of preimplantation genetic diagnosis, which may open a new round of progress in the field of assisted reproductive technologies and the genetics of early stages of human ontogenesis. PMID- 27183789 TI - [Telomere Recombination in Normal Mammalian Cells]. AB - Two mechanisms of telomere length maintenance are known to date. The first includes the use of a special enzymatic telomerase complex to solve the problems that arise during the replication of linear DNA in a normal diploid and part of tumor cells. Alternative lengthening of telomeres (ALT), which is based on the homologous recombination of telomere DNA, represents the second mechanism. Until recently, ALT was assumed to be expressed only in 15-20% of tumors lacking active telomerase and, together with telomerase reactivation represented one of two possibilities to overcome the replicative senescence observed in somatic mammalian cells due to aging or during cell culturing in vitro. Previously described sporadic cases of combinations of the two mechanisms of telomere length maintenance in several cell lines in vitro were attributed to the experimental design rather than to a real biological phenomenon, since active cellular division without active telomerase was considered to be the "gold standard" of ALT. The present review describes the morphological and functional reorganizations of mammalian telomeres observed with ALT activation, as well as recently observed,and well-documented cases of combinations between ALT-like and telomerase-dependent mechanisms in mammalian cells. The possible role of telomere recombination in telomerase-dependent cells is discussed. PMID- 27183790 TI - [Mutation Induction in the Mouse and Human Germline]. AB - The review describes the effects of exposure to mutagens on mutation induction in human and mouse germlines. The results of studies that evaluated inductions of mutations in human families subjected to irradiation are presented and discussed. The effects of exposure to mutagens on mutation induction in the mouse germline are also considered. We analyze and discuss the recent data on the genome-wide effects of irradiation on mutation induction in the mouse germline obtained by next-generation sequencing and comparative genome hybridization. PMID- 27183791 TI - [The Effect of Transcription on Enhancer Activity in Drosophila melanogaster]. AB - In higher eukaryotes, the level of gene transcription is under the control of DNA regulatory elements, such as promoter, from which transcription is initiated with the participation of RNA polymerase II and general transcription factors, as well as the enhancer, which increase the rate of transcription with the involvement of activator proteins and cofactors. It was demonstrated that enhancers are often located in the transcribed regions of the genome. We showed earlier that transcription negatively affected the activity of enhancers in Drosophila in model transgenic systems. In this study, we tested the effect of the distance between the leading promoter, enhancer, and target promoter on the inhibitory effect of transcriptions of different strengths. It was demonstrated that the negative effect of transcription remained, but weakened with increased distance between the leading promoter and enhancer and with decreased distance between the enhancer and target promoter. Thus, transcription can modulate the activity of enhancers by controlling its maximum level. PMID- 27183792 TI - [Distinctive Features of the Microbial Diversity and the Polyketide Synthase GenesSpectrum in the Community of the Endemic Baikal Sponge Swartschewskia papyracea]. AB - The diversity of the symbiotic community of the endemic Baikal sponge Swartschewskia papyracea was studied, and an analysis of the polyketide synthases genes spectrum in sponge-associated microorganisms was carried out. Six bacterial phyla were detected in the S. papyracea microbiome, namely, Verrucomicrobia, Cyanobacteria, Actinobacteria, Bacteroidetes, Proteobacteria, and Planctomycetes. Unlike the microbial associations of other freshwater sponges, the community under study was dominated by the Verrucomicrobia (42.1%) and Cyanobacteria (17.5%) phyla, while the proportion of the Proteobacteria was unusually low (9.7%). In the S. papyracea community metagenome, there were identified 18 polyketide synthases genes fragments, the closest homologs of which included the polyketide synthases of the microorganisms belonging to the bacterial phyla Cyanobacteria, Proteobacteria (Betaproteobacteria, Deltaproteobacteria, and Gammaproteobacteria classes), and Acidobacteria and to the eukaryotic algae of the Heterokonta phylum (Eustigmatophyceae class). Polyketide synthase sequences from S. papyracea formed three groups on the phylogenetic tree: a group of hybrid NRPS/PKS complexes, a group of cyanobacterial polyketide synthases, and a group of homologs of the eukaryotic alga Nannochloropsis galiana. Notably, the identified polyketide synthase genes fragments showed only a 57-88% similarity to the sequences in the databases, which implies the presence of genes controlling the synthesis of the novel, still unstudied, polyketide compounds in the S. papyracea community. It was proposed that the habitation conditions of S. papyracea affect the taxonomic composition of the microorganisms associated with the sponge, including the diversity of the producers of secondary metabolites. PMID- 27183793 TI - [The Inheritance of Endosperm Storage Proteins by the Line of the Saratovskaya 29 Cultivar of Common Wheat from its Parental Forms]. AB - We ran a comparative analysis of storage proteins (gliadins, high- (HMW) and low molecular-weight (LMW) glutenins, puroindolines, and exogenous alpha-amylase pest inhibitors) in the Saratovskaya 29 cultivar line from the collection of a genetic engineering laboratory, its parental forms (Albidum 24 and Lyutescens 55/11), and distant ancestors (Poltavka, Selivanovskiy Rusak, Sarroza, and tetraploid Beloturka). It was confirmed that the allelic states of storage proteins in the Gli-1, Gli-2 and Glu-1 loci originate from ancestral forms from the collection of the Vavilov Institute of Plant Industry. Moreover, new alleles were found in Lyutescense 55/11 (Glu-Ala) and Selivanovskiy Rusak (Glu-B1b) cultivars from the collection of the Institute of Cytology and Genetics. A new allelic state, Ha, was observed in the loci of the Poltavka cultivar as a soft-grain cultivar, and the ha allele was found in the hard-grain Albidum 24 and Sarroza cultivars. It was found that the expression rate of exogenous alpha-amylase inhibitors of pests in the Saratovskaya 29 cultivar line is lower than that of ancestral cultivars (Albidum 24, Sarroza, Poltavka, and Beloturka). Such inhibitors are absent in the paternal form Lyutescense 55/11. A high expression rate of protein pest inhibitors for exogenous alpha-amylases and puroindolines was observed in the Poltavka cultivar. The allelic composition of Glu-1 loci was newly studied in the Sarroza cultivar, which has some promising features. The Saratovskaya 29 cultivar line, on the basis of which a wide range of diverse lines were created in the Institute of Cytology and Genetics, is isogenic for all of the studied traits. PMID- 27183794 TI - DNA METHYLATION ANALYSIS DURING THE OPTIMIZATION OF Agrobacterium-MEDIATED TRANSFORMATION OF SOYBEAN. AB - Soybean is recognized as one of the plants which are very difficult to be transformed. Considering the low transformation efficiency of soybean, we aimed to determine the effect of 6-benzylaminopurine (6-BA), shoot induction time, and infection time of Agrobacterium on the clonal propagation of Glycine max. Results showed that 1.6 mg/L 6-BA could be optimal to promote the induction of adventitious shoots. An induction time of 15 d was considered optimal for the actual experiment involving soybean shoot induction. Agrobacterium was cultured until an OD600 = 0.8 was reached for an infection time of 30 min; this infection time may be optimal to promote soybean transformation. Whole genome DNA methylation was analyzed by high-performance liquid chromatography (HPLC) assisted quantification, and DNA methylation result is consistent with the phenotypic data of shoot development. In addition, two methylation-related genes (Decrease in DNA methylation 1 and DNA methyltransferases chromomethylase 2) were analyzed to determine expression differences by qRT-PCR in the shoots that were developed under different experimental conditions. In general, the expression values of these genes were normally downregulated under the recommended experimental conditions of soybean regeneration. This study showed the overall methylation changes in the in vitro culture of soybean, as affected by several variable parameters, which is useful to promote the transformation efficiency of soybean. PMID- 27183795 TI - GENETIC VARIATION AND IDENTIFICATION OF PROMISING SOUR CHERRIES INFERRED FROM MICROSATELLITE MARKERS. AB - The aim of this study was to identify the group of highly polymorphic microsatellite markers for identification of promising sour cherries. From among 30 tested microsatellite (SSR) markers, 19 were selected to profile genetic variation in sour cherries due to high polymorphisms. Results indicated a high level of polymorphism of the accessions based on these markers. Totally 148 alleles were generated at 19 SSR loci which 122 alleles were polymorphic. The number of total alleles per locus ranged from 2 to 15 with an average of 7.78 and polymorphism percentage varied from 50 to 100% with an average of 78.76%. Also, PIC varied from 0.47 to 0.89 with an average of 0.79 and heterozygosity ranged from 0.35 to 0.55 with a mean of 0.45. According to these results, these markers specially PMS3, PS12A02, PceGA34, BPPCT021, EMPA004, EMPA018, and Pchgms3 produced good and various levels of amplifications and showed high heterozygosity levels. By the way, the genetic similarity showed a high diversity among the sour cherries. Cluster analysis separated improved cultivars from promising sour cherries, and the PCoA supported the cluster analysis results. Since the studied sour cherries were superior to the improved cultivars and were separated from them in most groups, these sour cherries can be considered as distinct genotypes for further evaluations in the framework of breeding programs and new cultivar identification in cherries. Results also confirmed that the set of microsatellite markers employed in this study demonstrated usefulness of microsatellite markers for the identification of sour cherry genotypes. PMID- 27183797 TI - [Comparative Analysis of the Effectiveness of STR and SNP Markers for Intraspecific and Interspecific Differentiation of the Genus Ovis]. AB - A comparative study of the informativeness of SNP and STR markers for interspecific and intraspecific differentiation of the two species of the genus Ovis, snow sheep (O. nivicola) and domestic sheep (O. aries), was conducted. Eleven STR loci combined into two multiplex panels were examined. SNP analysis was performed with the DNA microarray OvineSNP50K BeadChip featuring 54241 SNPs. The possibility of clear differentiation of the studied Ovis species with both types of genetic markers was demonstrated. The advantages of SNP markers for intraspecific differentiation of the O. aries breeds and O. nivicola geographical groups were revealed. The areas of application of the studied types of DNA markers are discussed. PMID- 27183796 TI - [Genetic Connectivity Between Sympatric Populations of Closely Related Char Species, Dolly Varden Salvelinus malma and White Char Salvelinus albus]. AB - The closely related chars Salvelinus malma and Salvelinus albus, which sympatrically inhabit the Kamchatka River basin and Kronotsky Lake (Kamchatka), attract the attention of the researchers because of their debated origin and taxonomic status. Previous studies of sympatric populations of these chars revealed small but statistically significant genetic differences between these species at a number of molecular markers, suggesting the presence of the genetic exchange and hybridization. In this study, based on genotypic characterization of nine microsatellite loci, a considerable level of historical and contemporary genetic migration between sympatric populations of these chars was demonstrated. At the individual level a high degree of hybridization was observed, mainly among the Dolly Varden individuals from the studied populations. The obtained evidence on the genetic connectivity between sympatric S. malma and S. albus do not support the separate species status of S. albus. PMID- 27183798 TI - GENOME-WIDE MAPPING OF COPY NUMBER VARIATIONS IN COMMERCIAL HYBRID PIGS USING A HIGH-DENSITY SNP GENOTYPING ARRAY. AB - Copy number variations (CNVs) are important forms of structural variation in human and animals and can be considered as a major genetic component of phenotypic diversity. Here we used the Illumina PorcineSNP60 BeadChip V2 and a DLY [Duroc x (Large White x Landrace)] commercial hybrid population to identify 272 CNVs belonging to 165 CNV regions (CNVRs), of which 66 are new. As CNVRs are specific to origin of population, our DLY-specific data is an important complementary to the existing CNV map in the pig genome. Eight CNVRs were selected. for validation by quantitative real-time PCR (qRT-PCR) and the accurate rate was high (87.25%). Gene function analysis suggested that a common CNVR may play an important role in multiple traits, including growth rate and carcass quality. PMID- 27183799 TI - [The Dynamics of the Composition of mtDNA Haplotypes of the Ancient Population of the Altai Mountains from the Early Bronze Age (3rd Millennium BC) to the Iron Age (2nd-1st Centuries BC)]. AB - The mtDNA polymorphism in representatives of various archaeological cultures of the Developed Bronze Age, Early Scythian, and Hunnish-Sarmatian periods was analyzed (N = 34). It detected the dominance of Western-Eurasian haplotypes (70.6%) in mtDNA samples from the representatives of the ancient population of the Early Bronze Age--Iron Age on the territory of Altai Mountains. Since the 8th to the 7th centuries BC, a sharp increase was revealed in the Eastern-Eurasian haplogroups A, D, C, andZ (43.75%) as compared to previous cultures (16.7%). The presence of haplotype 223-242-290-319 of haplogroup A8 in Dolgans, Itelmens, Evens, Koryaks, and Yakuts indicates the possible long-term presence of its carriers in areas inhabited by these populations. The prevalence of Western Eurasian haplotypes is observed not only in the Altai Mountains but also in Central Asia (Kazakhstan) and the South of the Krasnoyarsk Krai. All of the three studied samples from the Western-Eurasian haplogroups were revealed to contain U, H, T, and HV. The ubiquitous presence of haplotypes of haplogroup H and some haplogroups of cluster U (U5al, U4, U2e, and K) in the vast territory from the Yenisei River basin to the Atlantic Ocean may indicate the direction of human settlement, which most likely occurred in the Paleolithic Period from Central Asia. PMID- 27183800 TI - [Marriage and Migratory Characteristics of the Urban Population of Karachay Cherkessia (the End of the 20th Century)]. AB - As part of systematic research carried out by the Laboratory of Genetic Epidemiology of the Research Center for Medical Genetics, the marriage and migratory structure of the urban population of Karachay-Cherkessia was studied. Numerical estimates of the population-genetic parameters were obtained from 11346 marriage records for 1990-2000. The endogamy, ethnic assortativeness, miscegenation and local inbreeding intensities, and mean-square migration for the four cities--Cherkessk, Karachayevsk, Ust-Dzheguta, and Teberda were estimated. It is shown that the autochthonic urban population is highly miscegenated, despite the traditional preference for monoethnic marriages. Half of the Russian urban population is migrant; the autochthonic urban population is substantially formed of Karachay-Cherkessia natives of. PMID- 27183801 TI - [Bioactive Effect of the Preparation Biostyl on the Reproductive Function of Different Genotypes of American Mink]. AB - The different role of coat color mutations in the American mink on the per os effect of the biologically active preparation Biostyl was shown. The number of kits per female was the same in all control genotypes, including Standard (+/+ +/+), sapphire (a/a p/p), and lavender (a/a m/m): 4.4 +/- 0.4, 4.4 +/- 0.5, and 4.3 +/- 0.5, respectively. Experimental groups of these genotypes have shown a great contrast among each other: stimulation of the reproductive function was 5.2 +/- 0.3 in Standard minks, while suppression of the reproductive function was 3.8 +/- 0.6, and 2.3 +/- 0.5 in the double recessive mutants sapphire and lavender, respectively. The differentiation in body mass between experimental and control newborn Standard kits was not revealed. A significant decrease in the body mass of newborn experimental sapphire kits as compared to control group in a sex specific manner was registered. PMID- 27183802 TI - Safety Precautions Always--Even When the Cameras Roll. PMID- 27183803 TI - Workers Not Always Using Their Fall Protection Equipment? PMID- 27183804 TI - Keep An Eye on Welding PPE. PMID- 27183805 TI - Curbing Hand Injury Risks. PMID- 27183806 TI - This Is Not Your Grandfather's Glove: Hand Protection in the Age of Performance Gloves. PMID- 27183807 TI - First Aid Readiness: Information, Preparation, Assessment, and Response. PMID- 27183808 TI - How ANSI is Leading the Way to Better First Aid in the Workplace. PMID- 27183809 TI - How Thermal Oxidation Can Increase the Sustainability of a Chemical Plant. PMID- 27183810 TI - Safety Communications for Today's Workforce. PMID- 27183811 TI - Comfort, Quality, Durability: Keys to Effective Protection. PMID- 27183812 TI - One Pair for Life. PMID- 27183813 TI - Carbon Dioxide Detection and Indoor Air Quality Control. AB - When building ventilation is reduced, energy is saved because it is not necessary to heat or cool as much outside air. Reduced ventilation can result in higher levels of carbon dioxide, which may cause building occupants to experience symptoms. Heating or cooling for ventilation air can be enhanced by a DCV system, which can save energy while providing a comfortable environment. Carbon dioxide concentrations within a building are often used to indicate whether adequate fresh air is being supplied to the building. These DCV systems use carbon dioxide sensors in each space or in the return air and adjust the ventilation based on carbon dioxide concentration; the higher the concentration, the more people occupy the space relative to the ventilation rate. With a carbon dioxide sensor DCV system, the fresh air ventilation rate varies based on the number ofpeople in the space, saving energy while maintaining a safe and comfortable environment. PMID- 27183814 TI - Production Materials Become Hazardous Waste Practically Overnight-EPA's Perspective on Abandoned Commercial Chemical Products. PMID- 27183815 TI - Data Center EH&S 101. PMID- 27183816 TI - Controlling the Climate of Safety Culture. PMID- 27183817 TI - Recasting Advanced Cultural Leadership. PMID- 27183818 TI - Optimal enlargement of the frontal sinus approach. AB - After recalling the main anatomical characteristics of the frontal sinuses, the authors describe the frontal craniotomy surgical procedure and its variants. A bicoronal skin incision is performed. An inferior-based pericranial flap is created, with its limits situated away from the osteotomies. Osteotomies are performed with an oscillating saw. The inferior osteotomy is horizontal, tangentially following the supraorbital margin as far as the lateral limit of each sinus. The osteotomy is continued medially as far as the nasion, passing an average of 3mm above the floor of the medial part of the sinuses, immediately above the frontonasal ducts. The superior osteotomy is performed in a vertical coronal plane through the summit of the sinuses. It is arc-shaped, concave downwards, joining the lateral extremities of the inferior osteotomy. The posterior wall of the sinus can be resected to perform frontal sinus cranialization, allowing access to the midline anterior cranial fossa. The posterior wall of the sinus is removed with a high-speed burr in the same way as the anterior wall. At the end of the procedure, the bone flap is sutured with nylon suture material and the pericranium is sutured over the bone flap. PMID- 27183819 TI - Technical aids for speech understanding in cochlear implanted adults using cell phones. AB - OBJECTIVES: The present study sought to assess (1) phone use habits and awareness of listening aids in adult cochlear implant bearers, and (2) objective and subjective benefit of listening aids for cell-phone communication. MATERIAL AND METHODS: A questionnaire was sent to 17 cochlear (Cochlear((r))) implanted adults to assess phone use and awareness of available listening aids. Speech perception without lip-reading was assessed in silence and in noise using Fournier dissyllabic word lists recorded on an iPhone 5C((r)), with and without listening aids. Subjective benefit was assessed according to listening aid system. RESULTS: Sixty-five percent of adult cochlear implant bearers regularly used a phone with all kinds of correspondent. Eighty-eight percent phoned only in quiet conditions; 53% did not answer unknown callers; 71% never used listening aids. Speech discrimination scores for disyllabic words recorded on the phone were respectively 69%, 63%, 45% and 16% in quiet and 50, 60 and 70dB SPL noise. Speech perception in quiet and noise was improved by listening aids; the Roger system was the most beneficial, followed by the FM system, then the inductive system. CONCLUSION: Listening aids are effective, but little known by adult cochlear implant bearers. PMID- 27183820 TI - The influence of larval competition on Brazilian Wolbachia-infected Aedes aegypti mosquitoes. AB - BACKGROUND: With field releases starting in Brazil, particular interest must be given to understanding how the endosymbiotic bacterium Wolbachia pipientis affects Aedes aegypti mosquitoes with a Brazilian genetic background. Currently, there is limited information on how the bacterium affects phenotypic traits such as larval development rate, metabolic reserves and morphometric parameters in Ae. aegypti. Here, we analyze for the first time, the effect of Wolbachia on these key phenotypes and consider how this might impact the potential of the bacterium as a disease control agent in Brazil. METHODS: We examined the influence of the wMel strain of Wolbachia in laboratory Ae. aegypti with a Brazilian genetic background, reared under different larval densities. Pupae formation was counted daily to assess differences in development rates. Levels of metabolic reserves and morphometric parameters were assessed in adults resulting from each larval condition. RESULTS: wMel infection led to more rapid larval development at higher densities for both males and females, with no effect under less crowded conditions in females. Infection also led to reduced body size at both high and low density, but not at intermediate density, although the scale of this difference was maintained regardless of larval density, in comparison to uninfected individuals. Wing shape also varied significantly between infected and uninfected mosquitoes due to larval density. Glycogen levels in uninfected mosquitoes decreased under higher larval density, but were consistently high with Wolbachia infection, regardless of larval density. CONCLUSIONS: We demonstrate that the wMel Wolbachia strain can positively influence some important host fitness traits, and that this interaction is directly linked to the conditions in which the host is reared. Combined with previously published data, these results suggest that this Wolbachia strain could be successfully used as part of the Eliminate Dengue Program in Brazil. PMID- 27183821 TI - Projected heat-related mortality under climate change in the metropolitan area of Skopje. AB - BACKGROUND: Excessive summer heat is a serious environmental health problem in Skopje, the capital and largest city of the former Yugoslav Republic of Macedonia. This paper attempts to forecast the impact of heat on mortality in Skopje in two future periods under climate change and compare it with a historical baseline period. METHODS: After ascertaining the relationship between daily mean ambient air temperature and daily mortality in Skopje, we modelled the evolution of ambient temperatures in the city under a Representative Concentration Pathway scenario (RCP8.5) and the evolution of the city population in two future time periods: 2026-2045 and 2081-2100, and in a past time period (1986-2005) to serve as baseline for comparison. We then calculated the projected average annual mortality attributable to heat in the absence of adaptation or acclimatization during those time windows, and evaluated the contribution of each source of uncertainty on the final impact. RESULTS: Our estimates suggest that, compared to the baseline period (1986-2005), heat-related mortality in Skopje would more than double in 2026-2045, and more than quadruple in 2081-2100. When considering the impact in 2081-2100, sampling variability around the heat mortality relationship and climate model explained 40.3 and 46.6 % of total variability. CONCLUSION: These results highlight the importance of a long-term perspective in the public health prevention of heat exposure, particularly in the context of a changing climate. PMID- 27183822 TI - Human newborn bacille Calmette-Guerin vaccination and risk of tuberculosis disease: a case-control study. AB - BACKGROUND: An incomplete understanding of the immunological mechanisms underlying protection against tuberculosis (TB) hampers the development of new vaccines against TB. We aimed to define host correlates of prospective risk of TB disease following bacille Calmette-Guerin (BCG) vaccination. METHODS: In this study, 5,726 infants vaccinated with BCG at birth were enrolled. Host responses in blood collected at 10 weeks of age were compared between infants who developed pulmonary TB disease during 2 years of follow-up (cases) and those who remained healthy (controls). RESULTS: Comprehensive gene expression and cellular and soluble marker analysis failed to identify a correlate of risk. We showed that distinct host responses after BCG vaccination may be the reason: two major clusters of gene expression, with different myeloid and lymphoid activation and inflammatory patterns, were evident when all infants were examined together. Cases from each cluster demonstrated distinct patterns of gene expression, which were confirmed by cellular assays. CONCLUSIONS: Distinct patterns of host responses to Mycobacterium bovis BCG suggest that novel TB vaccines may also elicit distinct patterns of host responses. This diversity should be considered in future TB vaccine development. PMID- 27183823 TI - AP endonuclease 1 prevents the extension of a T/G mismatch by DNA polymerase beta to prevent mutations in CpGs during base excision repair. AB - Dynamics of DNA methylation and demethylation at CpG clusters are involved in gene regulation. CpG clusters have been identified as hot spots of mutagenesis because of their susceptibility to oxidative DNA damage. Damaged Cs and Gs at CpGs can disrupt a normal DNA methylation pattern through modulation of DNA methylation and demethylation, leading to mutations and deregulation of gene expression. DNA base excision repair (BER) plays a dual role of repairing oxidative DNA damage and mediating an active DNA demethylation pathway on CpG clusters through removal of a T/G mismatch resulting from deamination of a 5mC adjacent to a guanine that can be simultaneously damaged by oxidative stress. However, it remains unknown how BER processes clustered lesions in CpGs and what are the consequences from the repair of these lesions. In this study, we examined BER of an abasic lesion next to a DNA demethylation intermediate, the T/G mismatch in a CpG dinucleotide, and its effect on the integrity of CpGs. Surprisingly, we found that the abasic lesion completely abolished the activity of thymine DNA glycosylase (TDG) for removing the mismatched T. However, we found that APE1 could still efficiently incise the abasic lesion leaving a 3-terminus mismatched T, which was subsequently extended by pol beta. This in turn resulted in a C to T transition mutation. Interestingly, we also found that APE1 3'-5' exonuclease activity efficiently removed the mismatched T, thereby preventing pol beta extension of the mismatched nucleotide and the resulting mutation. Our results demonstrate a crucial role of APE1 3'-5' exonuclease activity in combating mutations in CpG clusters caused by an intermediate of DNA demethylation during BER. PMID- 27183825 TI - An electronic alert to decrease Kayexalate ordering. AB - Important safety concerns have recently emerged regarding the use of sodium polystyrene sulfonate (Kayexalate), a cation-exchange resin commonly used for the treatment of hyperkalemia. We implemented an electronic alert system at a tertiary care academic medical center to warn providers of the safety concerns of Kayexalate. We assessed the number of Kayexalate prescriptions per month, as well as the number of grams of Kayexalate ordered per month, one year before versus one year after implementing the alert. The mean (+/-SD) number of Kayexalate orders decreased from 123 (+/-12) to 76 (+/-14) orders/month (38% absolute reduction, p < 0.001) after implementing the alert. Additionally, the mean (+/ SD) amount of Kayexalate prescribed decreased from 3332 (+/-329) to 1885 (+/-358) g/month (43% absolute reduction, p < 0.001). We conclude that an electronic alert is an effective tool to decrease Kayexalate ordering. PMID- 27183826 TI - Cervical metastases behavior of T1-2 squamous cell cancer of the oral mucosa. AB - OBJECTIVES: The clinical management of the neck of patients with early-stage oral squamous cell cancer (OSCC) is still controversially discussed in the current literature. This study analyzes histo-clinical factors influencing the occurrence of cervical lymph node metastases (CM). MATERIALS AND METHODS: In a retrospective mono-center study, patients with a primary T1-2 OSCC between 2000 and 2014 were analyzed regarding histo-clinical parameters possibly influencing the CM rate and the outcome. RESULTS: Two hundred eighty-five patients (66 %) were male and 146 female (44 %), with a mean age of 60 +/- 12 years at the time of diagnosis. Seventy-seven percent showed a positive risk profile (nicotine/alcohol) and 69 % underlying diseases. Forty-four percent of the patients were staged as T2 (30 % with CM). Advanced tumor size (T1 vs. T2) and grading (G1-2 vs. G3) were statistically significantly (p < 0.001) associated with the occurrence of CM. The localization within the oral cavity, age, gender, risk profile, or underlying diseases had no influence on CM occurrence. During the follow-up, tumor size (p = 0.001), CM (p < 0.001), and tumor relapse (p < 0.001) were significantly associated with a worse outcome. CONCLUSIONS: Early-stage OSCC showed aggressive lymphatic metastatic behavior that depends on the size and the grading of the tumor. CLINICAL RELEVANCE: A watch-and-wait policy as the primary management for cN0 may likely be inferior to a selective neck dissection for this patient group and should only be considered for very small tumors with a good differentiation. PMID- 27183824 TI - Adolescent alcohol exposure alters lysine demethylase 1 (LSD1) expression and histone methylation in the amygdala during adulthood. AB - Alcohol exposure in adolescence is an important risk factor for the development of alcoholism in adulthood. Epigenetic processes are implicated in the persistence of adolescent alcohol exposure-related changes, specifically in the amygdala. We investigated the role of histone methylation mechanisms in the persistent effects of adolescent intermittent ethanol (AIE) exposure in adulthood. Adolescent rats were exposed to 2 g/kg ethanol (2 days on/off) or intermittent n-saline (AIS) during postnatal days (PND) 28-41 and used for behavioral and epigenetic studies. We found that AIE exposure caused a long lasting decrease in mRNA and protein levels of lysine demethylase 1(Lsd1) and mRNA levels of Lsd1 + 8a (a neuron-specific splice variant) in specific amygdaloid structures compared with AIS-exposed rats when measured at adulthood. Interestingly, AIE increased histone H3 lysine 9 dimethylation (H3K9me2) levels in the central nucleus of the amygdala (CeA) and medial nucleus of the amygdala (MeA) in adulthood without producing any change in H3K4me2 protein levels. Acute ethanol challenge (2 g/kg) in adulthood attenuated anxiety-like behaviors and the decrease in Lsd1 + 8a mRNA levels in the amygdala induced by AIE. AIE caused an increase in H3K9me2 occupancy at the brain-derived neurotrophic factor exon IV promoter in the amygdala that returned to baseline after acute ethanol challenge in adulthood. These results indicate that AIE specifically modulates epizymes involved in H3K9 dimethylation in the amygdala in adulthood, which are possibly responsible for AIE-induced chromatin remodeling and adult psychopathology such as anxiety. PMID- 27183827 TI - Color stability of nanohybrid resin-based composites, ormocers and compomers. AB - OBJECTIVE: The aim of this study is to evaluate the color stability of two nanohybrid resin-based composites, two organic modified ceramic resin composites (ormocers) and a compomer, following their immersion during 4 weeks in four usual drinks. MATERIAL AND METHODS: Forty discs of each of the following materials were prepared: GrandioSO (GR), Esthet X (EX), Dyract EXTRA (DY), Ceram X duo (CX), and Admira Fusion (AD). The discs were polished and stored in distilled water during 24 h at 37 degrees C. Color according to the CIEL*a*b* scale was recoded. Ten randomly selected samples of each material were immersed in red wine (RW), coffee (CF), cola (CK), and distilled water (DW). The color was recorded after 1, 7, 21 and 28 days of immersion. The DeltaE values between the baseline color and each of the study timepoints were calculated. The data were analyzed based on the Kruskal-Wallis test, Wilcoxon test, and Mann-Whitney U test. RESULTS: After 1 day of immersion, all the materials showed DeltaE > 3.3, except EX, CF, and CX in CK. RD was the most staining beverage (DeltaE 15.36 to 31.09). EX and CX were significantly less stained than the rest of the materials (p < 0.05). CONCLUSIONS: All the staining solutions produced darkening beyond clinically acceptable limits. EX and CX were the materials who experimented less staining, followed by GD. AD and DY were the materials more stained. RW was the drink that produced more staining, followed by CF and CK. CLINICAL RELEVANCE: After 24 h of immersion in all the solutions, equivalent to 1 month of exposure in the mouth, the evaluated materials showed clinically unacceptable DeltaE values. PMID- 27183828 TI - Slow, progressive myopathy in neonatally treated patients with infantile-onset Pompe disease: a muscle magnetic resonance imaging study. AB - BACKGROUND: Patients with infantile-onset Pompe disease (IOPD) can be identified through newborn screening, and the subsequent immediate initiation of enzyme replacement therapy significantly improves the prognosis of these patients. However, they still present residual muscle weakness. In the present study, we used longitudinal muscle magnetic resonance imaging (MRI) to determine whether this condition is progressive. MATERIALS AND METHODS: A cohort of classic IOPD patients who were diagnosed through newborn screening were treated with recombinant human acid alpha-glucosidase (rhGAA) and followed prospectively from birth. The trunk (and abdominal wall), pelvis and upper thighs were scanned for muscle MRI every 2-3 years. Seven groups of muscles were individually scored from 0 to 4 based on the extent of their involvement, and the sum was correlated to the clinical manifestations. RESULTS: Twenty-four MRI scans from a total of 12 neonatally treated IOPD patients were analyzed in the present study. The median age at the time of MRI scanning was 4.2 years (13 days to 9 years). High intensity over the quadriceps on T2-weighted and short-tau inversion recovery images was observed in all scans and was followed by a decrease in muscle mass. Trunk muscle involvement was slower, except in one patient who exhibited progressive psoas atrophy. Among the 10 patients for whom follow-up scans were repeated more than 2 years after the first scan, four patients (40 %) showed increased myopathy severity. CONCLUSION: This prospective muscle MRI study provides evidence for the occurrence of slow, progressive muscle damage in neonatally treated IOPD patients during childhood. New treatment strategies are necessary to improve outcomes in these patients. PMID- 27183829 TI - Relationship between extrinsic factors and the acromio-humeral distance. AB - BACKGROUND: Maintenance of the subacromial space is important in impingement syndromes. Research exploring the correlation between biomechanical factors and the subacromial space would be beneficial. OBJECTIVES: To establish if relationship exists between the independent variables of scapular rotation, shoulder internal rotation, shoulder external rotation, total arc of shoulder rotation, pectoralis minor length, thoracic curve, and shoulder activity level with the dependant variables: AHD in neutral, AHD in 60 degrees arm abduction, and percentage reduction in AHD. DESIGN: Controlled laboratory study. METHOD: Data from 72 male control shoulders (24.28years STD 6.81 years) and 186 elite sportsmen's shoulders (25.19 STD 5.17 years) were included in the analysis. The independent variables were quantified and real time ultrasound was used to measure the dependant variable acromio-humeral distance. RESULTS: Shoulder internal rotation and pectoralis minor length, explained 8% and 6% respectively of variance in acromio-humeral distance in neutral. Pectoralis minor length accounted for 4% of variance in 60 degrees arm abduction. Total arc of rotation, shoulder external rotation range, and shoulder activity levels explained 9%, 15%, and 16%-29% of variance respectively in percentage reduction in acromio-humeral distance during arm abduction to 60 degrees . CONCLUSION: Pectorals minor length, shoulder rotation ranges, total arc of shoulder rotation, and shoulder activity levels were found to have weak to moderate relationships with acromio-humeral distance. Existence and strength of relationship was population specific and dependent on arm position. Relationships only accounted for small variances in AHD indicating that in addition to these factors there are other factors involved in determining AHD. PMID- 27183830 TI - Tactile acuity, body schema integrity and physical performance of the shoulder: A cross-sectional study. AB - BACKGROUND: Normative two-point discrimination thresholds (TPDTs) have been reported for different body regions and the relationships between TPDT and body schema integrity and physical performances are previously shown. However, such relationships with shoulder physical performance have not been investigated. OBJECTIVES: To quantify TPDT of the shoulders in healthy individuals and investigate whether TPDT and body schema integrity are related to physical performances and to identify the relationship between TPDT and body schema integrity. DESIGN: Cross-sectional study. RESULTS: Means (SD) of TPDTs of the dominant shoulder (DS) and non-dominant shoulder (NDS) were 44.8 (13.1) mm and 39.3 (9.5) mm respectively. TPDT scores were significantly negatively correlated with closed kinetic chain upper extremity stability test (CKCUEST) scores (r = 385, p = .036) and left/right judgement task (LRJT) response times (DS: rho = 449, p = .013 and NDS: rho = -388, p = .034). No significant correlations were found between TPDT and scores on functional throwing performance index (FTPI) and LRJT accuracy. However, positive moderate correlations were observed between LRJT and CKCUEST scores. CONCLUSIONS: TPDTs for ND and NDS in a cohort of adults have been documented. Tactile acuity and body schema integrity scores were correlated with superior performance in the upper limb stability task, indicating the potential role of tactile acuity and motor imagery training on maximizing physical performance. PMID- 27183831 TI - International consensus on the most useful physical examination tests used by physiotherapists for patients with headache: A Delphi study. AB - BACKGROUND: A wide range of physical tests have been published for use in the assessment of musculoskeletal dysfunction in patients with headache. Which tests are used depends on a physiotherapist's clinical and scientific background as there is little guidance on the most clinically useful tests. OBJECTIVES: To identify which physical examination tests international experts in physiotherapy consider the most clinically useful for the assessment of patients with headache. DESIGN/METHODS: Delphi survey with pre-specified procedures based on a systematic search of the literature for physical examination tests proposed for the assessment of musculoskeletal dysfunction in patients with headache. RESULTS: Seventeen experts completed all three rounds of the survey. Fifteen tests were included in round one with eleven additional tests suggested by the experts. Finally eleven physical examination tests were considered clinically useful: manual joint palpation, the cranio-cervical flexion test, the cervical flexion rotation test, active range of cervical movement, head forward position, trigger point palpation, muscle tests of the shoulder girdle, passive physiological intervertebral movements, reproduction and resolution of headache symptoms, screening of the thoracic spine, and combined movement tests. CONCLUSIONS: Eleven tests are suggested as a minimum standard for the physical examination of musculoskeletal dysfunctions in patients with headache. PMID- 27183833 TI - Corrigendum to 'Implementation fidelity of physiotherapist-delivered group education and exercise interventions to promote self-management in people with osteoarthritis and chronic low back pain: A rapid review Part II*' [Manual Therapy 20/2 (2014) 1-8]. PMID- 27183832 TI - Ageing and obesity indices influences the tactile acuity of the low back regions: A cross-sectional study. AB - BACKGROUND AND AIMS: Two-point discrimination threshold (TPDT) is increased in individuals with chronic low back pain. TPDT reference values and their determinants are required for clinical applications. Therefore, the aims of this research are to establish reference values for TPDT of the low back regions in healthy individuals, stratified for age, and to investigate the associations of demographic and anthropomorphic variables with TPDT. METHODS: Healthy individuals (n = 79) across four decades (Group-I:18-29; Group-II:30-39; Group-III:40-49; and Group-IV:50-59years) were recruited. A mechanical calliper tool was used to determine the low back TPDT (mm) using an adaptive staircase method. Descriptive statistics were calculated for TPDT for each age group. Paired t-tests (p <= 0.05) were used to assess within group differences in TPDT between body sides. Univariate and weighted least squared linear regression analyses were performed to investigate associations between TPDT estimates and demographics, and body mass index (BMI), waist hip ratio (WHR). RESULTS: Mean (SD) age = 38.3(12.2); 55 female; and 73 right lower limb dominant. Mean (SD) TPDT threshold for all age groups: right = 67.3(15.6), and left = 65.7(15.4). No significant differences between left and right sides of the low back except in group-IV (mean difference:5.6[0.7-10.5]; P = 0.028). A total of 18% of TPDT variance (adjusted R(2) = 0.183; beta = 0.6; p = <=0.001) of low back regions was explained by age with BMI and WHR weighted independently. CONCLUSIONS: Age, BMI, and WHR were independently associated with TPDT of the low back, and the influence of age was significantly influenced by obesity indices. PMID- 27183834 TI - Scapulothoracic muscle activity during elevation exercises measured with surface and fine wire EMG: A comparative study between patients with subacromial impingement syndrome and healthy controls. AB - BACKGROUND: The quality of the scapular movement depends on the coordinated activity of the surrounding scapulothoracic muscles. Besides the well-known changes in Trapezius and Serratus Anterior (SA) activity in patients with subacromial impingement syndrome (SIS), no studies exist that have investigated the activity of the smaller less superficial muscles that attach on the scapula (Pectoralis Minor (Pm), the Levator Scapulae (LS) and the Rhomboid Major (RM)) in a population with SIS, despite the hypothesized importance of these muscles in shoulder function. OBJECTIVES: To investigate if patients with shoulder impingement syndrome (SIS) show differences in deeper and superficial lying scapulothoracic muscle activity in comparison with a healthy control group during arm elevation tasks. STUDY DESIGN: Controlled laboratory study. METHODS: Activity of the deeper lying (LS, Pm and RM) and superficial lying scapulothoracic muscles (Trapezius and SA) was investigated with fine-wire and surface electromyography (EMG) in 17 subjects with SIS and 20 healthy subjects while performing 3 elevation tasks: scaption, wall slide and elevation with external rotation. Possible differences between the groups were studied with a linear mixed model (factor "group" and "exercise"). RESULTS: For the Pm only, a significant main effect for "Group" was found: during the elevation exercises, the Pm was significantly more active in the SIS group in comparison with the healthy controls. CONCLUSION: Patients with SIS show significantly higher Pm activity during elevation tasks in comparison with healthy controls. This study supports the idea of a possible role of the Pm in SIS. PMID- 27183835 TI - The short term effects of straight leg raise neurodynamic treatment on pressure pain and vibration thresholds in individuals with spinally referred leg pain. AB - BACKGROUND: Limited research exists for the effects of neurodynamic treatment techniques. Understanding short term physiological outcomes could help to better understand immediate benefits or harm of treatment. OBJECTIVES: To assess the short-term effects of a straight leg raise (SLR) tensioner 'intervention' on pressure pain thresholds (PPT) and vibration thresholds (VT), and establish if additional factors influence outcome in individuals with spinally referred leg pain. DESIGN: Experimental, repeated measures. METHODS: Sixty seven participants (mean age (SD) 52.9 (13.3), 33 female) with spinally referred leg pain were divided into 3 sub-groups: somatic referred pain, radicular pain and radiculopathy. Individuals were assessed for central sensitisation (CS) and completed 5 disability and psychosocial questionnaires. PPT and VT were measured pre and post a 3 * 1 min SLR tensioner intervention. RESULTS: No significant differences (p > 0.05) were found between the 3 groups for either outcome measure, or after treatment. Slight improvements in VT were seen in the radiculopathy group after treatment, but were not significant. Only 2 participants were identified with CS. Disability and psychological factors were not significantly different at baseline between the 3 sub-groups, and did not correlate with the outcome measures. CONCLUSIONS: No beneficial effects of treatment were found, but the trend for a decrease in VT indicated that even in individuals with radiculopathy, no detrimental changes to nerve function occurred. Psychosocial factors and levels of disability did not influence short term outcome of SLR treatment. PMID- 27183836 TI - Association between the 10 item Orebro Musculoskeletal Pain Screening Questionnaire and physiotherapists' perception of the contribution of biopsychosocial factors in patients with musculoskeletal pain. AB - BACKGROUND: Contrasting evidence exists on the ability of clinicians to identify biopsychosocial factors in patients with musculoskeletal pain compared to questionnaires. OBJECTIVE: Evaluate associations between two aspects of clinical practice used to assess biopsychosocial factor contribution in patient presentations (physiotherapist perceptions versus shortened 10-item Orebro Musculoskeletal Pain Screening Questionnaire (OMPSQ-10)). Potential influence of physiotherapists' training, experience and confidence level were assessed. STUDY DESIGN: Observational. METHODS: 90 musculoskeletal pain patients completed the OMPSQ-10 prior to their initial assessment. Independently, 19 treating physiotherapists provided their perception of contribution of biopsychosocial factors to the patient presentation. Pragmatic comparison of physiotherapist perceptions and the OMPSQ-10 was made with Spearman's correlations. RESULTS: Fair correlation existed between physiotherapists' perception of overall contribution of biopsychosocial factors to the patients' presentation and the OMPSQ-10 (0.39). There where moderate correlations for the domains of recovery expectancy (0.53), self-perceived ability to work (0.52) and ability to sleep (0.54). There where fair correlations for anxiety (0.33) and depression (0.32), and a poor correlation for fear (0.10). Correlations were influenced by therapist training in psychosocial aspects of pain, experience and confidence. CONCLUSIONS: Physiotherapists' perceptions on biopsychosocial contributing factors to overall presentation of patients with musculoskeletal pain were reasonably correlated with a number of the domains in the OMPSQ-10. However, correlations for anxiety, depression and fear were not as good. This may reflect a lack of adequate training and/or the inadequacy of single questionnaire items to capture complex issues such as pain-related fear. Screening questionnaires are recommended as an adjunct to clinician perceptions. PMID- 27183838 TI - Genomic Regions Associated with Sheep Resistance to Gastrointestinal Nematodes. AB - Genetic markers for sheep resistance to gastrointestinal parasites have long been sought by the livestock industry as a way to select more resistant individuals and to help farmers reduce parasite transmission by identifying and removing high egg shedders from the flock. Polymorphisms related to the major histocompatibility complex and interferon (IFN)-gamma genes have been the most frequently reported markers associated with infection. Recently, a new picture is emerging from genome-wide studies, showing that not only immune mechanisms are important determinants of host resistance but that gastrointestinal mucus production and hemostasis pathways may also play a role. PMID- 27183837 TI - Risk factors for small-for-gestational-age and preterm births among 19,269 Tanzanian newborns. AB - BACKGROUND: Few studies have differentiated risk factors for term-small for gestational age (SGA), preterm-appropriate for gestational age (AGA), and preterm SGA, despite evidence of varying risk of child mortality and poor developmental outcomes. METHODS: We analyzed birth outcome data from singleton infants, who were enrolled in a large randomized, double-blind, placebo-controlled trial of neonatal vitamin A supplementation conducted in Tanzania. SGA was defined as birth weight <10th percentile for gestation age and sex using INTERGROWTH standards and preterm birth as delivery at <37 complete weeks of gestation. Risk factors for term-SGA, preterm-AGA, and preterm-SGA were examined independently using log-binomial regression. RESULTS: Among 19,269 singleton Tanzanian newborns included in this analysis, 68.3 % were term-AGA, 15.8 % term-SGA, 15.5 % preterm AGA, and 0.3 % preterm-SGA. In multivariate analyses, significant risk factors for term-SGA included maternal age <20 years, starting antenatal care (ANC) in the 3(rd) trimester, short maternal stature, being firstborn, and male sex (all p < 0.05). Independent risk factors for preterm-AGA were maternal age <25 years, short maternal stature, firstborns, and decreased wealth (all p < 0.05). In addition, receiving ANC services in the 1(st) trimester significantly reduced the risk of preterm-AGA (p = 0.01). Significant risk factors for preterm-SGA included maternal age >30 years, being firstborn, and short maternal stature which appeared to carry a particularly strong risk (all p < 0.05). CONCLUSION: Over 30 % of newborns in this large urban and rural cohort of Tanzanian newborns were born preterm and/or SGA. Interventions to promote early attendance to ANC services, reduce unintended young pregnancies, increased maternal height, and reduce poverty may significantly decrease the burden of SGA and preterm birth in sub-Saharan Africa. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) - ACTRN12610000636055 , registered on 3(rd) August 2010. PMID- 27183839 TI - The Emerging Role and Promise of Long Noncoding RNAs in Lung Cancer Treatment. AB - Lung cancer is the leading cause of cancer death around the world. The advanced discovery of numerous long noncoding RNAs (lncRNAs) has dramatically changed the understanding of biology of human cancers, including lung cancer. LncRNAs are a group of noncoding RNAs (ncRNAs) with a length greater than 200 nucleotides with limited or no protein-coding capacity. Increasing evidence has shown that specific lncRNAs may be implicated in the process of tumorigenesis. Because of their roles in the regulation of multiple molecular pathways associated with changes in gene expression, lncRNAs can serve as potential diagnostic biomarkers or therapeutic targets in lung cancer. Importantly, dysregulated lncRNAs is reported to be correlated with the sensitivity of lung cancer cells to anticancer therapies, including chemotherapy, molecular-targeted therapy, etc. Herein, we review the recent progress of lncRNAs in lung cancer, with a particular focus on the multiple molecular roles of regulatory lncRNAs on the molecular signaling pathways involved in tumorigenesis and the resistance to such therapies. PMID- 27183840 TI - Polymer-Based and pH-Sensitive Nanobiosensors for Imaging and Therapy of Acidic Pathological Areas. AB - Nanobiosensors with high sensitivity and specificity have shown great potential in the detection of diseases. The incorporation of therapeutic agents with nanobiosensors allows the simultaneous diagnosis and therapy of diseases. The delivery of nanobiosensors and therapeutic agents using polymers is a common strategy to improve imaging and therapeutic efficacies. These polymers play important roles in several aspects during a successful delivery process, such as increasing the stability and biocompatibility of the nanobiosensors and improving their cell endocytosis. The pH-sensitivity of the nanobiosensors endows them with various capabilities, such as enabling the selective targeting of pathological areas, activation of imaging signals and controlled release of payloads. This review focuses on the design, preparation and characterization of polymer-based and pH-sensitive nanobiosensors and the in intro/in vivo assessment of their ability to serve as efficient agents for the diagnosis and therapy of acidic pathological areas. PMID- 27183841 TI - Is There a Space-Based Technology Solution to Problems with Preclinical Drug Toxicity Testing? AB - Even the finest state-of-the art preclinical drug testing, usually in primary hepatocytes, remains an imperfect science. Drugs continue to be withdrawn from the market due to unforeseen toxicity, side effects, and drug interactions. The space program may be able to provide a lifeline. Best known for rockets, space shuttles, astronauts and engineering, the space program has also delivered some serious medical science. Optimized suspension culture in NASA's specialized suspension culture devices, known as rotating wall vessels, uniquely maintains Phase I and Phase II drug metabolizing pathways in hepatocytes for weeks in cell culture. Previously prohibitively expensive, new materials and 3D printing techniques have the potential to make the NASA rotating wall vessel available inexpensively on an industrial scale. Here we address the tradeoffs inherent in the rotating wall vessel, limitations of alternative approaches for drug metabolism studies, and the market to be addressed. Better pre-clinical drug testing has the potential to significantly reduce the morbidity and mortality of one of the most common problems in modern medicine: adverse events related to pharmaceuticals. PMID- 27183842 TI - Small vertebral cross-sectional area and tall intervertebral disc in adolescent idiopathic scoliosis. AB - BACKGROUND: When compared to boys, girls have smaller vertebral cross-sectional area, which conveys a greater spinal flexibility, and a higher prevalence of adolescent idiopathic scoliosis. OBJECTIVE: To test the hypothesis that small vertebral cross-sectional area and tall intervertebral disc height are structural characteristics of patients with adolescent idiopathic scoliosis. MATERIALS AND METHODS: Using multiplanar imaging techniques, measures of vertebral cross sectional area, vertebral height and intervertebral disc height in the lumbar spine were obtained in 35 pairs of girls and 11 pairs of boys with and without adolescent idiopathic scoliosis of the thoracic spine matched for age, height and weight. RESULTS: Compared to adolescents without spinal deformity, girls and boys with adolescent idiopathic scoliosis had, on average, 9.8% (6.68 +/- 0.81 vs. 7.40 +/- 0.99 cm(2); P = 0.0007) and 13.9% (8.22 +/- 0.84 vs. 9.55 +/- 1.61 cm(2); P = 0.009) smaller vertebral cross-sectional dimensions, respectively. Additionally, patients with adolescent idiopathic scoliosis had significantly greater values for intervertebral disc heights (9.06 +/- 0.85 vs. 7.31 +/- 0.62 mm and 9.09 +/- 0.87 vs. 7.61 +/- 1.00 mm for girls and boys respectively; both P <= 0.011). Multiple regression analysis indicated that the presence of scoliosis was negatively associated with vertebral cross-sectional area and positively with intervertebral disc height, independent of sex, age and body mass index. CONCLUSION: We provide new evidence that girls and boys with adolescent idiopathic scoliosis have significantly smaller vertebral cross-sectional area and taller intervertebral disc heights - two major structural determinants that influence trunk flexibility. With appropriate validation, these findings may have implications for the identification of children at the highest risk for developing scoliosis. PMID- 27183843 TI - The Effect of Sex and Gender on Diabetic Complications. AB - While in non-diabetic people the risk for cardiovascular disease is higher in men, diabetes completely reverts this sex-gender difference conferring to women a greater burden of cardiovascular complications. Additionally, all risk factors associated with cardiovascular disease appear to be more active in diabetic females than in their male counterparts. The reasons of this different impact of diabetes between genders are not completely clear. The aim of this review is trying to clarify these issues in a sex and gender perspective. Both genetic and hormonal factors are at the basis of sex-gender differences in diabetes, even do not explain the totality of data. Possibly women arrive later and in worse conditions to the diagnosis of diabetes, receive both diagnostic and therapeutic supports in a lesser measure and, finally, reach therapeutic goals as recommended by guidelines in a lesser extent. Further aspects of sex-gender differences in diabetic complications are represented by a more frequent prevalence of drug side effects in women, as well as by increased resistance to the action of drugs used in prevention or in the therapy of cardiovascular diseases. As to microvascular complications, the issue of sex-gender differences is even more complex, with some important differences emerging in experimental models 'in vitro', as well as in human pathology 'in vivo'. The main problem, however, also in this case, is that it is difficult to differentiate how common pathogenetic mechanisms acting in diabetes may differently impact between genders. In conclusion what is evident is that diabetes represents a 'risk magnifier' for the damage of both micro and macrovessels differently in men and in women. This issue deserves, therefore, a more careful approach from people involved in both clinical aspects and research regarding diabetes and its complications, in a sex-gender oriented perspective. PMID- 27183845 TI - Performance of diagnostic tests in an intensive follow-up protocol for patients with American Joint Committee on Cancer (AJCC) stage IIB, IIC, and III localized primary melanoma: A prospective cohort study. AB - BACKGROUND: There is no international consensus on optimal follow-up schedules and which supplementary tests should be used after resection of a primary melanoma. OBJECTIVE: We sought to analyze the performance of the follow-up components and identify procedures that detect melanoma metastasis earlier. METHODS: This was a prospective cohort from 290 consecutive patients given a diagnosis of stage IIB, IIC, and III melanoma. Patients were followed up with an intensive protocol based on imaging studies (computed tomography of the chest, abdomen, and pelvis, and brain magnetic resonance imaging), periodic laboratory tests, regular physical examinations, and patient self-examinations. RESULTS: A total of 2382 clinical examinations and 3069 imaging tests were performed. The patients completed 899.8 person-years of follow-up, with a median of 2.5 years. In all, 115 recurrences in 290 patients were recorded, of which computed tomography detected 48.3%; brain magnetic resonance imaging, 7.6%; laboratory test, 2.5%; physician, 23.7%; and patient, 17.8%. LIMITATIONS: Patients with stage III melanoma were not systematically classified into subgroups and overall survival was not evaluated. CONCLUSION: We observed that this intensive monitoring is appropriate for early detection of recurrence in stage IIB, IIC, and III melanoma. Prompt diagnosis of metastasis and the recent development of new therapeutic targets may improve overall survival. PMID- 27183846 TI - Cardiovascular risk in patients with alopecia areata (AA): A propensity-matched retrospective analysis. AB - BACKGROUND: The cardiovascular risk of patients with alopecia areata (AA) is not well characterized, with limited studies evaluating the risk of acute myocardial infarction (AMI) and ischemic stroke. OBJECTIVE: We sought to determine the risk for patients with AA to develop subsequent stroke and AMI. METHODS: We conducted propensity-matched retrospective analysis between January 1, 2000, and January 1, 2010, from Brigham and Women's Hospital and Massachusetts General Hospital in Boston, MA. A comprehensive research patient data repository search was done for International Classification of Diseases, Ninth Revision code 704.01 and cases were verified using a natural language processing program. Propensity score matching was used to identify controls for AA cases based on age, race, gender, smoking status, and history of hypertension, diabetes, and hyperlipidemia. RESULTS: We identified 1377 cases of AA matched with 4131 controls. Patients with AA had decreased odds for developing stroke (odds ratio 0.39, 95% CI 0.18-0.87) and a trend toward decreased risk of AMI (odds ratio 0.91, 95% CI 0.59-1.39). LIMITATIONS: This was a retrospective study using a clinical database. CONCLUSION: Patients with AA had decreased risk for stroke and AMI, although not statistically significant. Further studies are needed to confirm these findings in other AA cohorts and to elucidate a potential mechanism. PMID- 27183848 TI - Australia tax increases to price cigarettes out of reach. PMID- 27183844 TI - Classification of Therapeutic and Experimental Drugs for Brown Adipose Tissue Activation: Potential Treatment Strategies for Diabetes and Obesity. AB - OBJECTIVE: Increasing efforts are being made towards pharmacologic activation of brown adipose tissue (BAT) in animals and humans for potential use in the treatment of obesity and diabetes. We and others have reported a number of animal studies using either experimental or therapeutic drugs. There are now efforts to translate these findings to human studies. The goal of this review is to evaluate the various drugs currently being used that have the potential for BAT activation. METHODS: Drugs were classified into 4 classes based on their mechanism of action. Class 1 drugs include the use of beta3 adrenoceptor agonists for BAT activation. Class 2 drugs include drugs that affect norepinephrine levels and activate BAT with the potential of reducing obesity. Class 3 includes activators of peroxisome proliferator-activated receptor-gamma in pursuit of lowering blood sugar, weight loss and diabetes and finally Class 4 includes natural products and other emerging drugs with limited information on BAT activation and their effects on diabetes and weight loss. RESULTS: Class 1 drugs are high BAT activators followed by Class 2 and 3. Some of these drugs have now been extended to diabetes and obesity animal models and human BAT studies. Drugs in Class 3 are used clinically for Type 2 diabetes, but the extent of BAT involvement is unclear. CONCLUSION: Further studies on the efficacy of these drugs in diabetes and measuring their effects on BAT activation using noninvasive imaging will help in establishing a clinical role of BAT. PMID- 27183847 TI - Germ cell and tumor associated piRNAs in the medaka and Xiphophorus melanoma models. AB - BACKGROUND: A growing number of studies report an abnormal expression of Piwi interacting RNAs (piRNAs) and the piRNA processing enzyme Piwi in many cancers. Whether this finding is an epiphenomenon of the chaotic molecular biology of the fast dividing, neoplastically transformed cells or is functionally relevant to tumorigenesisis is difficult to discern at present. To better understand the role of piRNAs in cancer development small laboratory fish models can make a valuable contribution. However, little is known about piRNAs in somatic and neoplastic tissues of fish. RESULTS: To identify piRNA clusters that might be involved in melanoma pathogenesis, we use several transgenic lines of medaka, and platyfish/swordtail hybrids, which develop various types of melanoma. In these tumors Piwi, is expressed at different levels, depending on tumor type. To quantify piRNA levels, whole piRNA populations of testes and melanomas of different histotypes were sequenced. Because no reference piRNA cluster set for medaka or Xiphophorus was yet available we developed a software pipeline to detect piRNA clusters in our samples and clusters were selected that were enriched in one or more samples. We found several loci to be overexpressed or down-regulated in different melanoma subtypes as compared to hyperpigmented skin. Furthermore, cluster analysis revealed a clear distinction between testes, low grade and high-grade malignant melanoma in medaka. CONCLUSIONS: Our data imply that dysregulation of piRNA expression may be associated with development of melanoma. Our results also reinforce the importance of fish as a suitable model system to study the role of piRNAs in tumorigenesis. PMID- 27183849 TI - New risk loci for endometrial cancer identified. PMID- 27183850 TI - [Growth hormone treatment in small for gestational age children in Spain]. AB - INTRODUCTION: Since its approval by the European Medicines Agency, a great number of patients born small for gestational date have received recombinant growth hormone treatment in Spain. The aim of this study is to analyse its outcome in the setting of ordinary clinical practice. METHODS: Information was gathered from the registers of the assessment boards that authorise all growth hormone treatments prescribed in public hospitals in six autonomic communities (regions). RESULTS: Valid data from 974 patients was obtained. All of them complied with criteria established by the European Medicines Agency. Patients in the sample were smaller in length than weight at birth, with their median target height being below 1 standard deviation (SD), and 23% of them had been delivered prematurely. Treatment was started at 7.2+/-2.8 years (mean+/-SD). The mean patient height at start was -3.1+/-0.8 SD. They gained 0.7+/-0.2 SD in the first year, and 1.2+/-0.8 SD after two years. Final height was attained by 8% of the sample, reaching -1.4+/-0.7 SD. CONCLUSIONS: These results are similar to other Spanish and international published studies, and are representative of the current practice in Spain. Despite treatment being started at a late age, adequate growth is observed in the short term and in the final height. Up to a 24% of patients show a poor response in the first year. PMID- 27183851 TI - [Atypical presentations of juvenile xanthogranuloma]. PMID- 27183852 TI - Open abdominal aortic aneurysm repair is still necessary in an era of advanced endovascular repair. AB - OBJECTIVE: Recent advances in endovascular aneurysm repair have overcome substantial anatomic barriers associated with short and challenging necks. With greater range to treat more difficult anatomy from an endovascular approach, one would assume the need of open surgical repair (OSR) would be diminished. The purpose of our study was to determine the need for OSR for abdominal aortic aneurysms, in a tertiary academic setting, with a moderate volume (10-15 cases/year) of fenestrated endografting being performed. METHODS: An Institutional Review Board approved retrospective review was performed of all patients who underwent elective aortic aneurysm repair between January 2010 and July 2014. Computed tomography scans for patients who underwent OSR were reviewed and anatomic characteristics obtained. Instructions for use of (IFU) a commercially available fenestrated device (Cook Medical, Bloomington, Ind) were used to determine if open repair patients had anatomy amenable to advanced endovascular repair. RESULTS: During the study interval, 415 patients underwent abdominal aortic aneurysm repair. Of those patients who underwent elective aneurysm repair, 105 patients had OSR. The study subsequently excluded 11 patients because they underwent secondary interventions after a failed endovascular repair and thus were not further evaluated. Also excluded were 18 patients who had OSR for an emergency intervention. The remaining 76 patients (35 female, 41 male; average age, 72 +/- 8 years) had OSR and were outside the IFU of the fenestrated endovascular aneurysm repair (FEVAR) device. The average diameter of the abdominal aorta was 5.9 cm. Indications for OSR were an aneurysm neck <4 mm (71%), inclusion of at least 1 visceral vessel (69.7%), unilateral iliac artery aneurysms (15.5%), bilateral iliac artery aneurysms (14.3%), iliac artery tortuosity >40 degrees of angulation (37.6%), extensive aortic thrombus (23.2%), and aortic neck angulation >45 degrees (11.8%). Rejected patients had an average of 1.7 +/- 0.8 anatomic constraints (range 1-4) that prevented use of the FEVAR device. CONCLUSIONS: With evidence to support the strict adherence to IFU protocols of the FEVAR device in patients, our institution's practice has been to continue to perform open abdominal aortic aneurysm repair for patients with anatomy outside device protocols. Although it was thought that the decreased requirement of aortic neck required to deploy an endograft would lead to an increased patient population amenable to endovascular repair, there is still a clinically significant need for open aortic surgery. PMID- 27183853 TI - Influence of gender and use of regional anesthesia on carotid endarterectomy outcomes. AB - OBJECTIVE: Carotid endarterectomy (CEA) is the most commonly performed surgical procedure to reduce the risk of stroke. The operation may be performed under general anesthesia (GA) or regional anesthesia (RA). We used a national database to determine how postoperative outcomes were influenced by gender and type of anesthesia used. METHODS: All patients who underwent CEA between 2005 and 2011 were identified from the American College of Surgeons National Surgical Quality Improvement Program database (N = 41,442). Incidence of stroke and myocardial infarction (MI) within 30 days as well as other postoperative complications, operative time, and hospital length of stay were examined in groups separated by gender and anesthesia type. Multivariable logistic regression with effect modification was used to determine significant risk-adjusted differences between genders and type of anesthesia to assess outcomes after CEA. RESULTS: The male-to female ratio among CEA cases performed was approximately 3:2. Most cases were performed under GA (85% male patients, 86% female patients). Adjusted multivariable analysis showed no statistical difference in rates of MI and stroke based on gender or type of anesthesia used. There were, however, higher 30-day postoperative local complications and MI (both P < .05) in those who had GA vs RA regardless of gender before adjustment. Total operative time was decreased (mean difference, -8.15 minutes; 95% confidence interval, -10.09 to -6.21; P < .001) and length of stay was increased (mean difference, 0.34 day; 95% confidence interval, 0.14-0.54; P < .02) in women, with statistical significance, whether RA or GA was used. CONCLUSIONS: On adjusted multivariate analysis, there is no statistically significant difference in postoperative incidence of MI or stroke between men and women undergoing CEA. Use of RA vs GA did not affect this finding. Furthermore, there was no correlation between gender and the type of anesthesia chosen. Women, however, experienced decreased operative times and increased length of stay regardless of anesthesia type. PMID- 27183854 TI - Results of standard suprarenal fixation endografts for abdominal aortic aneurysms with neck length <=10 mm in high-risk patients unfit for open repair and fenestrated endograft. AB - OBJECTIVE: The aim of this study was to evaluate long-term outcomes of endovascular aneurysm repair (EVAR) using a standard suprarenal fixation endograft in abdominal aortic aneurysms (AAAs) with infrarenal neck length <=10 mm (short-neck AAA [SN-AAA]). METHODS: From 2005 to 2010, data of high-risk patients with SN-AAA, unfit for open repair (OR) and fenestrated EVAR, were prospectively collected. Follow-up was performed by duplex ultrasound and contrast-enhanced ultrasound or computed tomography angiography at 1 month, 6 months, and 12 months and yearly thereafter. The primary end point was AAA related mortality. Secondary end points were proximal type I endoleak, freedom from reintervention, and AAA shrinkage (>5 mm). RESULTS: Sixty patients (mean age, 74.9 +/- 6.2 years; American Society of Anesthesiologists class 3 [85%] and class 4 [15%]) were enrolled. The mean aneurysm diameter and neck length and diameter were 60.4 +/- 12.2 mm, 8.4 +/- 1.6 mm, and 23.5 +/- 3 mm, respectively. Four (7%) patients were symptomatic and 15 (25%) had rapid AAA enlargement (>5 mm/6 months). Cook Zenith Flex (Cook Medical, Bloomington, Ind) endografts (32) and Medtronic Endurant (Medtronic, Santa Rosa, Calif) endografts (28) were implanted. The mean follow-up was 51 +/- 18 months. Survival at 5 years was 70%. There were three (5%) type I endoleaks. One was sealed by endovascular reintervention, and two (3%) underwent conversion to OR for AAA rupture at 8 and 36 months. Both patients died (2/60; 3% AAA-related mortality). Reinterventions were necessary for another five (8%) patients, and they were not proximal neck related. Freedom from reintervention at 5 years was 90%. In 49 (82%) cases, there was AAA shrinkage; the AAA diameter remained stable in nine (15%) and increased in two (3%) cases. Severe proximal angle (alpha neck angle >=60 degrees) was associated with type I endoleak (P = .010) and reinterventions (P = .010). The neck length <7 mm (P = .030) was associated with reinterventions (P = .017). CONCLUSIONS: Suprarenal fixation EVAR in SN-AAA with a straight, not wide neck and 7- to 10-mm aortic neck length can be considered safe and effective in patients who are unfit for OR and fenestrated EVAR. For these cases, long-term data showed acceptable results in preventing aneurysm rupture and related mortality. PMID- 27183855 TI - Explantation of infected aortic aneurysm and endograft with ascending aorta to mesenteric bypass for mesenteric ischemia. AB - A 65-year-old man presented with an infected perivisceral aortic aneurysm after previous treatment of an abdominal aortic aneurysm with an endograft. On presentation, he was septic and had occlusion of the celiac, superior mesenteric, inferior mesenteric, and bilateral renal arteries. He underwent a three-stage procedure: first, axillobifemoral bypass; then resection of the thoracoabdominal aorta; and finally bypass from the ascending aorta to the celiac and superior mesenteric arteries with a rifampin-soaked Gelsoft graft (Vascutek, Renfrewshire, Scotland). The abdominal pain resolved, and the patient remains symptom free 10 months postoperatively. This rare surgical revascularization technique offered a nontraditional solution to a difficult surgical issue. PMID- 27183856 TI - Improving mortality trends for hospitalization of aortic dissection in the National Inpatient Sample. AB - OBJECTIVE: Population-based assessment of aortic dissection (AD) hospitalizations in the general United States population is limited. We assessed the current trends in AD admissions and in-hospital mortality for surgical and medical AD treatment. METHODS: Patients admitted for primary diagnosis of AD were identified from the National Inpatient Sample database (2003-2012). Patients were identified by International Classification of Diseases-Ninth Revision diagnosis codes and categorized by treatment type: type A open surgical repair (TASR), type B open surgical repair (TBSR), thoracic endovascular aortic repair (TEVAR), and medical management (MM). Our primary outcomes were to evaluate admission trends and in hospital mortality of AD. Secondary outcomes included postoperative complications. We used weighted national estimates of admissions to assess trends over time using linear regression. We also identified factors associated with mortality via a hierarchical multivariable logistic regression model. RESULTS: We identified 15,641 patients (60.7% male; mean age, 63.5 years) admitted with a primary diagnosis of AD between 2003 and 2012. Intervention types included TASR in 3253 (20.8%), TBSR in 3007 (19.2%), TEVAR in 1417 (9.1%), and MM in 7964 (50.9%). Overall weighted admissions for AD increased significantly, from 6980 in 2003 to 8875 in 2012 (P < .01, test of trend), with increases in admission for TASR, from 1143 in 2003 to 2130 in 2012 (P < .01, test of trend), and TEVAR from 96 in 2005 to 1130 in 2012 (P < .01, test of trend). TBSR and MM admissions were stable, with TBSR admissions at 1519 in 2003 and 1540 in 2012 (P = .9, test of trend) and MM admissions at 4319 in 2003 and 4075 in 2012 (P = .8, test of trend). During the same interval, overall in-hospital mortality rates for AD decreased from 18.1% to 13.0% (P < .01, test of trend). When stratified by intervention type, mortality rates decreased for TASR, from 20.5% to 14.8% (P < .01, test of trend), for TBSR, from 18.0% to 14.3% (P = .03, test of trend), and for MM, from 17.5% to 13.9% (P < .01, test of trend). Mortality rates for TEVAR were stable, with an average mortality of 7.9% (P = .8, test of trend) during the study period. Factors associated with increased mortality included older age, Caucasian race, nonelective admission, pre-existing peripheral vascular disease, and acute postoperative complication of myocardial infarction, stroke, or kidney failure. Admissions at a center with high surgical volume were associated with a decreased mortality for TBSR admissions only (odds ratio, 0.55; 95% confidence interval, 0.4-0.7). CONCLUSIONS: Overall and surgical admission rates for AD appear to be increasing, and in-hospital mortality rates are decreasing. TEVAR mortality remains mostly unchanged, however, suggesting targets for further improvement in mortality for AD treatment. Decreased mortality for TBSR at centers with a high surgical volume may suggest a need for regionalization of AD care. PMID- 27183857 TI - Equivalent outcomes with standard and heparin-bonded expanded polytetrafluoroethylene grafts used as conduits for hemodialysis access. AB - BACKGROUND: Obtaining and maintaining dialysis access after failure of autologous access sites remains a significant concern for patients on hemodialysis. Polytetrafluoroethylene (PTFE) is the most common conduit used. Heparin-bonded expanded PTFE (HB-PTFE) grafts have recently been introduced as an improved conduit, with suggestions that HB offers benefits because of its resistance to thrombosis. In this retrospective study, the outcomes of HB-PTFE were compared with standard wall PTFE (S-PTFE) arteriovenous grafts (AVGs). METHODS: From January 2004 to December 2014, 483 adults (46% male; mean age, 60 years; range, 25-87 years) with end-stage renal disease underwent placement of AVGs (234 HB PTFE and 248 S-PTFE). The two groups did not differ significantly in demographics or access history. Patency, reintervention, infection, and functional dialysis rates were examined. RESULTS: Technical success was 99% in HB-PTFE and 98% in S PTFE. The 30-day major adverse cardiovascular events were 2% in HB-PTFE and 3% in S-PTFE. Mean time to access was 5.1 +/- 1.8 weeks for HB-PTFE and 6.9 +/- 1.9 weeks for S-PTFE (P = .0001). Median follow-up was 23 months. The 2-year primary, assisted primary, and secondary patency rates were 20% +/- 7% vs 18% +/- 8% (P = .85), 35% +/- 8% vs 28% +/- 7% (P = .51), and 38% +/- 6% vs 36% +/- 7% (P = .83) for HB-PTFE vs S-PTFE, respectively. Both groups underwent a similar number of secondary interventions (2.1 and 1.9 interventions per person-year of follow-up for HB-PTFE vs S-PTFE respectively; P = .87). There were no significant differences in infection (11% vs 12%) or pseudoaneurysm formation (5% vs 6%) between HB-PTFE and S-PTFE groups. Functional dialysis durations were equivalent between HB-PTFE and S-PTFE groups. CONCLUSIONS: HB-PTFE grafts offer no distinct advantage over S-PTFE grafts for hemodialysis and should not be considered a preferential conduit for AVG. PMID- 27183858 TI - Use of a proactive duplex ultrasound protocol for hemodialysis access. AB - OBJECTIVE: Arteriovenous fistula (AVF) creation is the preferred approach for hemodialysis access; however, the maturation of AVFs is known to be poor. We established a proactive early duplex ultrasound (DUS) surveillance protocol for evaluating AVFs before attempted access. This study determined the effect of this protocol related to improving AVF maturation. METHODS: From 2008 to 2013, 153 patients received new upper extremity AVFs and an early DUS surveillance protocol at a single academic institution. The protocol involved an early DUS evaluation before hemodialysis cannulation of the AVF at 4 to 8 weeks after AVF creation. A positive DUS result was identified as a peak systolic velocity of >375 cm/s or a >50% stenosis on gray scale imaging, along with decreased velocity in the outflow vein. Patients with positive DUS findings underwent prophylactic endovascular or open intervention to assist with AVF maturation. Nature of secondary interventions, as well as AVF patency and maturation, were assessed. Overall clinical outcomes and fistula patency were investigated. RESULTS: During the study period, 183 upper extremity AVFs were created in 153 patients, including 82 radiocephalic, 63 brachiocephalic, and 38 brachiobasilic AVFs. A mortality rate of 43% (n = 66) was observed in a median follow-up period of 34.5 months (interquartile range, 19.6-46.9). A total of 164 early DUS were performed at a median of 6 weeks (interquartile range, 3.4-9.6 weeks) after the initial creation. Early DUS showed nine AVFs were occluded and were excluded from further analysis. Hemodynamically significant lesions were found in 62 AVFs (40%); however, only 17 (11%) were associated with an abnormal physical examination. Positive DUS finding prompted a secondary intervention in 81% of the patients. Among those with positive early DUS findings, AVF maturation was 70% in those undergoing a secondary intervention compared with 25% in those not undergoing a prophylactic intervention (P = .011). Primary-assisted patency for AVFs with early positive and negative DUS findings were 83% and 96% at 6 months, 64% and 89% at 1 year, and 52% and 82% at 2 years, respectively (P < .001). CONCLUSIONS: Early DUS surveillance of AVFs before initial access is reasonable to identify problematic AVFs that may not be reliably detected on clinical examination. Although DUS criteria for AVFs have yet to be universally accepted, proactive early postoperative DUS interrogation assists in the early detection of dysfunctional AVFs and improvement of fistula maturation. Despite improved patency in those with positive DUS findings who undergo prophylactic secondary intervention, overall patency remains inferior to those without an abnormality detected on early DUS imaging. PMID- 27183859 TI - Clinical outcomes and material properties of in situ fenestration of endovascular stent grafts. AB - OBJECTIVE: In situ fenestration of endovascular stent grafts has been used as a method for branch vessel revascularization in urgent and emergent settings. The objective of this manuscript was to review the clinical and experimental evidence related to this technique. METHODS: PubMed, MEDLINE, and Embase databases were searched for papers published until December 2015 describing in situ fenestration of aortic stent grafts. Benchtop, animal, and human studies were included. RESULTS: The literature review identified 118 articles, of which 28 studies were selected for inclusion. These included 16 clinical papers (2 case series and 14 case reports) reporting in situ fenestration of 46 aortic branch vessels in 44 patients. There were 42 retrograde and 4 antegrade instances of in situ fenestration. The most frequent target vessel for in situ fenestration was the left subclavian artery (72%), and the most frequent indication for stent graft implantation was a degenerative aortic aneurysm (43%). Technical success was reported in 44 of 46 attempted fenestrations (96%). The combined rate of perioperative mortality, stroke, and paralysis was 7%. In situ fenestration was predominantly performed with the Talent (Medtronic, Santa Rosa, Calif) stent graft (54%), followed by the Zenith (Cook Medical, Bloomington, Ind) stent graft (37%) and the TAG (W. L. Gore & Associates, Newark, Del) stent graft (9%). In vitro benchtop evaluations of in situ fenestration showed minimal change in fenestration size after 1 year of pulsatile fatigue testing. The use of energy based fenestration techniques (radiofrequency or laser) has been associated with less fabric fraying than in needle-based techniques. The larger caliber initial fenestration created by these devices also avoids the need for cutting balloons, which have also been linked with increased fabric tears and fraying of the fibers surrounding the fenestration. In addition, the Zenith stent graft was shown in benchtop testing to be the strongest in postfenestration mechanical testing, but it was also the most resistant to balloon dilation. CONCLUSIONS: In the short to moderate term, in situ fenestration appears to be a reasonable and effective method to extend the proximal landing zone for revascularization of the left subclavian artery. However, longer follow-up is needed to fully assess the long term durability of this procedure. Based on studies of material properties, an energy-based fenestration technique (radiofrequency or laser) is recommended, along with the avoidance of cutting balloons for dilation of the fenestration. PMID- 27183860 TI - Preparation of five 3-MCPD fatty acid esters, and the effects of their chemical structures on acute oral toxicity in Swiss mice. AB - BACKGROUND: 3-monochloro-1, 2-propanediol fatty acid esters (3-MCPDEs) comprise a group of food toxicants formed during food processing. 3-MCPDEs have received increasing attention concerning their potential negative effects on human health. However, reports on the toxicity of 3-MCPD esters are still limited. To determine the effects of fatty acid substitutions on the toxicity of their esters, 1 stearic, 1-oleic, 1-linoleic, 1-linoleic-2-palmitic and 1-palmitic-2-linoleic acid esters of 3-MCPD were synthesized and evaluated with respect to their acute oral toxicities in Swiss mice. RESULTS: 3-MCPDEs were obtained through the reaction of 3-MCPD and fatty acid chlorides, and their purities and structures were characterized by ultraperformance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF-MS), infrared, 1 H and 13 C spectroscopic analyses. Medial lethal doses of 1-stearic, 1-oleic, 1-linoleic, 1-linoleic-2 palmitic and 1-palmitic-2-linoleic acid esters were 2973.8, 2081.4, 2016.3, 5000 and > 5000 mg kg-1 body weight. For the first time, 3-MCPDEs were observed for their toxic effects in the thymus and lung. In addition, major histopathological changes, as well as blood urea nitrogen and creatinine, were examined for mice fed the five 3-MCPDEs. CONCLUSION: The results from the present study suggest that the degree of unsaturation, chain length, number of substitution and relative substitution locations of fatty acids might alter the toxicity of 3 MCPDEs. (c) 2016 Society of Chemical Industry. PMID- 27183861 TI - A recessive syndrome of intellectual disability, moderate overgrowth, and renal dysplasia predisposing to Wilms tumor is caused by a mutation in FIBP gene. AB - Clinical classification of overgrowth syndromes represents a challenge since a wide spectrum of disorders result in marked overgrowth. Therefore, there is a continuous effort to identify the genetic basis of these disorders that will eventually facilitate their molecular classification. Here, we have identified the genetic etiology and the pathogenetic mechanism underlying a rare autosomal recessive overgrowth syndrome in three affected siblings. The overgrowth phenotype in the patients was accompanied by developmental delay, learning disabilities, and variable congenital abnormalities. To elucidate the genetic etiology of the disorder, whole-genome genotyping and whole-exome sequencing were used. The disease was mapped to 3p21.1-p14.2 and 11q13.1-q13.4, where an in-frame insertion (c.175_176insTAA) in FIBP gene was revealed. The resulting indel (p.H59LN) was predicted to change the protein conformation with likely deleterious effect on its function as one of the fibroblast growth factor signaling mediators. In vitro cellular proliferation assay and in situ hypridization in vivo were then performed to understand the pathophysiology of the disease. The patients' skin fibroblasts showed an increased proliferation capacity compared to the controls' explaining the observed overgrowth phenotype. In addition, we detected Fibp expression most notably in the brains of mice embryos suggesting a possible effect on cognitive functions early in development. To date, only one patient has been reported with a homozygous nonsense mutation in FIBP exhibiting an overgrowth syndrome with multiple congenital abnormalities. Taken all together, these findings provide convincing evidence implicating FIBP aberrations in the newly recognized overgrowth syndrome and expand the associated phenotypes to include possible Wilms tumor predisposition. (c) 2016 Wiley Periodicals, Inc. PMID- 27183862 TI - Vascular Density in Retina and Choriocapillaris as Measured by Optical Coherence Tomography Angiography. AB - PURPOSE: To measure the density of the superficial retinal small vessel network (SRSVN), superficial retinal capillary network (SRCN), deep retinal capillary network (DRCN), and choriocapillaris and the size of the foveal avascular zone (FAZ) in the superficial retinal layer in normal eyes. DESIGN: Prospective observational cross-sectional study. METHODS: In healthy Chinese volunteers, the retinal and choroidal vasculature was visualized by split-spectrum amplitude decorrelation angiography-associated optical coherence tomography (RTVueXR Avanti device; Optovue Inc, Fremont, California, USA). RESULTS: Among 105 healthy participants (age: 35.9 +/- 13.8 years) mean FAZ measured 0.35 +/- 0.12 mm(2), and mean density of SRSVN, SRCN, DRCN, and choriocapillaris was 8.54% +/- 0.92%, 31.8% +/- 2.6%, 45.8% +/- 3.3%, 44.4% +/- 3.3%, and 44.5% +/- 2.7%, respectively. In multivariate analysis, higher SRSVN density was associated with younger age (P = .001; standardized regression coefficient beta: -0.28), male sex (P = .008; beta: -0.23), lower SRCN density (P < .001; beta: -0.40), and larger mean choriocapillaris vessel diameter (P = .001; beta: 0.30). Higher SRCN density was correlated with male sex (P = .007; beta: -0.19), lower SRSVN density (P < .001; beta: -0.44), and higher density of the radial peripapillary capillary density (P = .004; beta: 0.20). Higher DRCN density was correlated with younger age (P < .001; beta: -0.31), female sex (P = .002; beta: 0.22), higher SRCN density (P < .001; beta: 0.38), and higher choriocapillaris density (P < .001; beta: 0.39). Higher choriocapillaris network density in the central region was associated with higher DRCN density (P < .001; beta: 0.43) and lower radial peripapillary capillary density (P = .005; beta: -0.26). All retinal vascular parameters were not significantly correlated with axial length or subfoveal choroidal thickness. CONCLUSIONS: The density of the macular vascular networks decreases with older age and is independent of axial length and subfoveal choroidal thickness in healthy individuals. PMID- 27183863 TI - Erratum to: Enhanced osseous integration of human trabecular allografts following surface modification with bioactive lipids. PMID- 27183865 TI - Aneurysm of the internal jugular vein. PMID- 27183864 TI - Absence of chromosomal translocations and protein expression of ALK in sinonasal adenocarcinomas. AB - INTRODUCTION: Chromosomal translocations at 2p23 cause overexpression of anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase involved in signalling pathways that regulate cell proliferation. This translocation occurs in 5% of lung adenocarcinoma and has been demonstrated to be useful as a therapeutic target for crizotinib. sinonasal adenocarcinomas (SNAC) are histologically similar to lung adenocarcinomas; the aim of this study was to evaluate the presence of ALK alterations in SNAC. METHOD: Break-apart fluorescent in-situ hybridization was used to analyse the presence of ALK translocations in 96 tumour samples. In addition, ALK protein expression was studied by immunohistochemistry. RESULTS: The samples of SNAC did not show ALK translocation. Moreover, ALK protein expression was absent in all cases. CONCLUSIONS: These results suggest that ALK is not involved in SNAC. PMID- 27183866 TI - Nasal septal schwannoma: An extremely rare tumor. PMID- 27183867 TI - Trigeminal trophic syndrome: An unusual cause of nasal ulceration. PMID- 27183868 TI - A Novel Slicing Method for Thin Supercapacitors. AB - Thin and flexible supercapacitors with low cost and individual variation are fabricated by a new and efficient slicing method. Tunable output voltage and energy can be realized with a high specific capacitance of 248.8 F g(-1) or 150.8 F cm(-3) , which is well maintained before and after bending. PMID- 27183869 TI - Genome-wide identification and functional annotation of miRNAs in anti inflammatory plant and their cross-kingdom regulation in Homo sapiens. AB - MicroRNAs (miRNAs) are newly discovered non-coding small (~17-24 nucleotide) RNAs that regulate gene expression of its target mRNA at the post-transcriptional levels. In this study, total 12,593 ESTs of Curcuma longa were taken from database of expressed sequence tags (dbEST) and clustered into 2821 contigs using EGassembler web server. Precursor miRNAs (pre-miRNAs) were predicted from these contigs that folded into stem-loop structure using MFold server. Thirty-four mature C. longa miRNAs (clo-miRNAs) were identified from pre-miRNAs having targets involved in various important functions of plant such as self-defence, growth and development, alkaloid metabolic pathway and ethylene signalling process. Sequence analysis of identified clo-miRNAs indicated that 56% miRNAs belong to ORF and 44% belong to non-ORF region. clo-mir-5 and clo-mir-6 were established as the conserved miRNAs, whereas clo-mir-20 was predicted to be the most stable miRNA. Phylogenetic analysis carried out by molecular evolutionary genetics analysis (MEGA) software indicated close evolutionary relationship of clo-mir-5075 with osa-MIR5075. Further, identified clo-miRNAs were checked for their cross-kingdom regulatory potential. clo-mir-14 was found to regulate various gene transcripts in humans that has been further investigated for its biostability in foetal bovine serum (FBS). The results indicated higher degree of stability of clo-mir-14 (48 h) in FBS. Thus, contribution of this miRNA to the cellular immune response during the inflamed condition of rheumatoid arthritis and adequate stability may make it a good choice for the therapeutic agent in near future. PMID- 27183870 TI - Prognostic significance of K-ras mutations in pancreatic cancer: a meta-analysis. AB - BACKGROUND: K-ras gene mutations are common in patients with pancreatic cancer (PC); however, their prognostic value for PC remains inconclusive. This meta analysis was performed to quantitatively evaluate the association between K-ras mutations and survival in patients with pancreatic cancer. METHODS: We performed a comprehensive search of electronic sources including MEDLINE (via PubMed), Web of Science, and the Cochrane Library. The search covered a publication period from inception to November 2015. RESULTS: Seventeen studies with a total of 2249 patients with pancreatic cancer were included in the tissue detection of this study. The meta-analysis indicated a significant association between mutant K-ras genes and overall survival (OS) (HR = 1.51, 95% CI 1.32-1.72, P < 0.001). Moreover, further subgroup analyses by ethnicity, publication year, therapy method, cancer resectability, and gene detection method all revealed that pancreatic cancer patients with the K-ras mutation had significantly poorer OS (P < 0.05). And results from four studies with 225 patients focused on plasma K-ras mutations enhanced such association (HR = 2.23, 95% CI 1.69-2.95, P < 0.001). CONCLUSIONS: As a prediction of poor prognosis, the detection of K-ras mutations may be a useful prognostic factor for pancreatic cancer patients. PMID- 27183871 TI - Scapulohumeral rhythm relative to active range of motion in patients with symptomatic rotator cuff tears. AB - BACKGROUND: Some patients with rotator cuff tears feel pain without functional limitation, whereas others show a decrease in range of motion. To investigate this distinction, the scapulohumeral rhythm was used to conduct a functional evaluation of shoulder joints' coordination. The objective was to characterize patients according to their active range of motion without pain and their scapulohumeral rhythm compared with healthy individuals. MATERIALS AND METHODS: Fourteen patients with rotator cuff tears and 14 healthy individuals were set up with 35 reflective markers on the trunk and upper limb tracked by an optoelectronic system to measure the scapulohumeral rhythm. Five scapular plane maximal arm elevations were executed without pain. Patients were separated by maximal arm elevation of 85 degrees (category A) and 40 degrees (category B). Three-way mixed-design analysis of variance with factors of group (patients and healthy), arm elevation, and motion direction was applied to the scapulohumeral rhythm. RESULTS: A main effect of group (P = .032) was observed in patients in category A, who showed inferior scapulohumeral rhythm. An interaction between group and arm elevation (P = .044) was observed for patients in category B, where their scapulohumeral rhythm increased more during arm elevation than in the healthy individuals. CONCLUSIONS: Patients who reached at least 85 degrees compensated for the loss of glenohumeral motion by increased scapulothoracic contribution, suggesting that structural damage interferes with motion mechanics. In contrast, patients who reached less range of motion underused the scapulothoracic joint, which is likely to create subacromial impingement at low arm elevation. A patient's maximal range of motion without pain may indicate a pattern of scapulohumeral rhythm alteration. PMID- 27183872 TI - Facile Synthesis of Yolk-Shell-Structured Triple-Hybridized Periodic Mesoporous Organosilica Nanoparticles for Biomedicine. AB - The synthesis of mesoporous nanoparticles with controllable structure and organic groups is important for their applications. In this work, yolk-shell-structured periodic mesoporous organosilica (PMO) nanoparticles simultaneously incorporated with ethane-, thioether-, and benzene-bridged moieties are successfully synthesized. The preparation of the triple-hybridized PMOs is via a cetyltrimethylammonium bromide-directed sol-gel process using mixed bridged silsesquioxanes as precursors and a following hydrothermal treatment. The yolk shell-structured triple-hybridized PMO nanoparticles have large surface area (320 m(2) g(-1) ), ordered mesochannels (2.5 nm), large pore volume (0.59 cm(3) g(-1) ), uniform and controllable diameter (88-380 nm), core size (22-110 nm), and shell thickness (13-45 nm). In vitro cytotoxicity, hemolysis assay, and histological studies demonstrate that the yolk-shell-structured triple-hybridized PMO nanoparticles have excellent biocompatibility. Moreover, the organic groups in the triple-hybridized PMOs endow them with an ability for covalent connection of near-infrared fluorescence dyes, a high hydrophobic drug loading capacity, and a glutathione-responsive drug release property, which make them promising candidates for applications in bioimaging and drug delivery. PMID- 27183874 TI - Reply. PMID- 27183873 TI - Methylation of arginine by PRMT1 regulates Nrf2 transcriptional activity during the antioxidative response. AB - The cap 'n' collar (CNC) family of transcription factors play important roles in resistance of oxidative and electrophilic stresses. Among the CNC family members, NF-E2-related factor 2 (Nrf2) is critical for regulating the antioxidant and phase II enzymes through antioxidant response element (ARE)-mediated transactivation. The activity of Nrf2 is controlled by a variety of post translational modifications, including phosphorylation, ubiquitination, acetylation and sumoylation. Here we demonstrate that the arginine methyltransferase-1 (PRMT1) methylates Nrf2 protein at a single residue of arginine 437, both in vitro and in vivo. Using the heme oxygenase-1 (HO-1) as a model of phase II enzyme gene, we found that methylation of Nrf2 by PRMT1 led to a moderate increase of its DNA-binding activity and transactivation, which subsequently protected cells against the tBHP-induced glutathione depletion and cell death. Collectively, our results define a novel modification of Nrf2, which operates as a fine-tuning mechanism for the transcriptional activity of Nrf2 under the oxidative stress. PMID- 27183875 TI - Effect of the particle-hole channel on BCS-Bose-Einstein condensation crossover in atomic Fermi gases. AB - BCS-Bose-Einstein condensation (BEC) crossover is effected by increasing pairing strength between fermions from weak to strong in the particle-particle channel, and has attracted a lot of attention since the experimental realization of quantum degenerate atomic Fermi gases. Here we study the effect of the (often dropped) particle-hole channel on the zero T gap Delta(0), superfluid transition temperature Tc, the pseudogap at Tc, and the mean-field ratio 2Delta(0)/, from BCS through BEC regimes, using a pairing fluctuation theory which includes self consistently the contributions of finite-momentum pairs and features a pseudogap in single particle excitation spectrum. Summing over the infinite particle-hole ladder diagrams, we find a complex dynamical structure for the particle-hole susceptibility chiph, and conclude that neglecting the self-energy feedback causes a serious over-estimate of chiph. While our result in the BCS limit agrees with Gor'kov et al., the particle-hole channel effect becomes more complex and pronounced in the crossover regime, where chiph is reduced by both a smaller Fermi surface and a big (pseudo)gap. Deep in the BEC regime, the particle-hole channel contributions drop to zero. We predict a density dependence of the magnetic field at the Feshbach resonance, which can be used to quantify chiph and test different theories. PMID- 27183877 TI - Clinical considerations on the posology of direct oral anticoagulants. AB - The efficacy of dicoumarin anticoagulants has been shown in patients with nonvalvular atrial fibrillation. However, they have drawbacks such as the need to adjust the dosage and the interaction with drugs and food. Direct oral anticoagulants are an effective and safe alternative and have a less complicated clinical management. There is considerable debate on the selection criteria for the posology regimens of direct oral anticoagulants. The differences among them and their administration regimens have raised questions about the clinical, pharmacokinetic and pharmacodynamic selection criteria that support the posology. This review critically analyses the available evidence and its impact on the final selection of the dosage regimen. PMID- 27183879 TI - PET/CT in primary mediastinal large B-cell lymphoma responding to rituximab-CHOP. PMID- 27183878 TI - Reporting results for deep molecular responses in chronic myeloid leukemia. PMID- 27183881 TI - Development of a rechargeable optical hydrogen peroxide sensor - sensor design and biological application. AB - Hydrogen peroxide (H2O2) is an important member of the reactive oxygen species (ROS) family. Among ROS, H2O2 is considered the most long-lived and can accumulate inside and outside of cells, where it is involved in both vital (signaling) and deadly (toxic) reactions depending on its concentration. Quantifying H2O2 within biological samples is challenging and often not possible. Here we present a quasi-reversible fiber-optic sensor capable of measuring H2O2 concentrations ranging from 1-100 MUM within different biological samples. Based on a Prussian blue/white redox cycle and a simple sensor recharging and readout strategy, H2O2 can be measured with high spatial (~500 MUm) and temporal (~30 s) resolution. The sensor has a broad applicability both in complex environmental and biomedical systems, as demonstrated by (i) H2O2 concentration profile measurements in natural photosynthetic biofilms under light stress reaching H2O2 concentrations as high as 15 MUM, and (ii) the quantification of the transient increase of the extracellular concentration of H2O2 during stimulation of neutrophils. PMID- 27183876 TI - Increased Gut Redox and Depletion of Anaerobic and Methanogenic Prokaryotes in Severe Acute Malnutrition. AB - Severe acute malnutrition (SAM) is associated with inadequate diet, low levels of plasma antioxidants and gut microbiota alterations. The link between gut redox and microbial alterations, however, remains unexplored. By sequencing the gut microbiomes of 79 children of varying nutritional status from three centers in Senegal and Niger, we found a dramatic depletion of obligate anaerobes in malnutrition. This was confirmed in an individual patient data meta-analysis including 107 cases and 77 controls from 5 different African and Asian countries. Specifically, several species of the Bacteroidaceae, Eubacteriaceae, Lachnospiraceae and Ruminococceae families were consistently depleted while Enterococcus faecalis, Escherichia coli and Staphylococcus aureus were consistently enriched. Further analyses on our samples revealed increased fecal redox potential, decreased total bacterial number and dramatic Methanobrevibacter smithii depletion. Indeed, M. smithii was detected in more than half of the controls but in none of the cases. No causality was demonstrated but, based on our results, we propose a unifying theory linking microbiota specificity, lacking anaerobes and archaea, to low antioxidant nutrients, and lower food conversion. PMID- 27183880 TI - Direct determination of three-phase contact line properties on nearly molecular scale. AB - Wetting phenomena in multi-phase systems govern the shape of the contact line which separates the different phases. For liquids in contact with solid surfaces wetting is typically described in terms of contact angle. While in macroscopic systems the contact angle can be determined experimentally, on the molecular scale contact angles are hardly accessible. Here we report the first direct experimental determination of contact angles as well as contact line curvature on a scale of the order of 1nm. For water nucleating heterogeneously on Ag nanoparticles we find contact angles around 15 degrees compared to 90 degrees for the corresponding macroscopically measured equilibrium angle. The obtained microscopic contact angles can be attributed to negative line tension in the order of -10(-10) J/m that becomes increasingly dominant with increasing curvature of the contact line. These results enable a consistent theoretical description of heterogeneous nucleation and provide firm insight to the wetting of nanosized objects. PMID- 27183882 TI - Filter-Based Dispersion-Managed Versatile Ultrafast Fibre Laser. AB - We present the operation of an ultrafast passively mode-locked fibre laser, in which flexible control of the pulse formation mechanism is readily realised by an in-cavity programmable filter the dispersion and bandwidth of which can be software configured. We show that conventional soliton, dispersion-managed (DM) soliton (stretched-pulse) and dissipative soliton mode-locking regimes can be reliably targeted by changing the filter's dispersion and bandwidth only, while no changes are made to the physical layout of the laser cavity. Numerical simulations are presented which confirm the different nonlinear pulse evolutions inside the laser cavity. The proposed technique holds great potential for achieving a high degree of control over the dynamics and output of ultrafast fibre lasers, in contrast to the traditional method to control the pulse formation mechanism in a DM fibre laser, which involves manual optimisation of the relative length of fibres with opposite-sign dispersion in the cavity. Our versatile ultrafast fibre laser will be attractive for applications requiring different pulse profiles such as in optical signal processing and optical communications. PMID- 27183883 TI - Aortic root remodeling leads to good valve stability in acute aortic dissection and preexistent root dilatation. AB - OBJECTIVES: To evaluate the long-term results of aortic root remodeling in the setting of acute aortic dissection type A (AADA). METHODS: Between October 1995 and May 2013, a total of 215 patients were treated surgically for AADA. Of these, 59 patients with AADA (<2 weeks from onset, age 56 +/- 16 years, 53 males) with a root diameter of >=43 to 45 mm (depending on patient size) underwent aortic root remodeling and were analyzed further. Reimplantation was performed in 7 patients; root replacement with a mechanical composite graft, in 16 patients; root replacement with a stentless biological prosthesis, in 10 patients; and tubular ascending aortic replacement, in 133 patients. RESULTS: Reexploration for bleeding was performed in 10 patients (17%; 8% since 2007). Early mortality was 6.8%; no patient died after 2002. Actuarial survival at 10 years was 72% +/- 6%. One patient underwent aortic valve replacement for recurrent cusp prolapse at 1 year after surgery. In this operation, cusp configuration was assessed by eyeballing until 2003. The rate of freedom from proximal reoperation at 10 years was 98% +/- 2%. Using a Cox proportional hazards model, no independent predictors for survival and reoperation after remodeling were found. Advanced age and concomitant coronary artery bypass grafting were identified as independent predictors for survival in all 215 patients with AADA. CONCLUSIONS: Root remodeling allows for stable valve preservation in patients with AADA and preexistent root dilatation. PMID- 27183884 TI - Accuracy of transesophageal echocardiography in the identification of postoperative intramural ventricular septal defects. AB - BACKGROUND: Intramural ventricular septal defects (VSDs), residual interventricular communications occurring after repair of conotruncal defects, are associated with poor postoperative outcomes. The ability of intraoperative transesophageal echocardiography (TEE) to identify intramural VSDs has not yet been evaluated. METHODS: Intraoperative TEE and postoperative transthoracic echocardiography (TTE) data in all patients undergoing all biventricular repair of conotruncal anomalies in our hospital between January 1, 2006, and June 30, 2013, were reviewed. The ability of TEE to accurately identify residual defects was assessed using postoperative TTE as the reference imaging modality. RESULTS: Intramural VSDs occurred in 34 of 337 patients evaluated; 19 were identified by both TTE and TEE, and 15 were identified by TTE only. Sensitivity was 56% and specificity was 100% for TEE to identify intramural VSDs. Peripatch VSDs were identified in 90 patients by both TTE and TEE, in 53 by TTE only, and in 15 by TEE only, yielding a sensitivity of 63% and specificity of 92%. Of the VSDs requiring catheterization or surgical reintervention, 6 of 7 intramural VSDs and all 5 peripatch VSDs were identified by intraoperative TEE. TEE guided the intraoperative decision to return to cardiopulmonary bypass (CPB) in an attempt to close residual defects in 12 patients with intramural VSDs and in 4 patients with peripatch VSDs seen after initial CPB; of these, 10 intramural VSDs and all 4 peripatch VSDs resolved or became smaller on final intraoperative TEE. CONCLUSIONS: TEE has modest sensitivity but high specificity for identifying intramural VSDs and can detect most defects requiring reintervention. Repeat attempts at closure in the index operation may successfully correct intramural VSDs identified by TEE. PMID- 27183885 TI - Reproducible research and model validation: Are we ready for new standards? PMID- 27183887 TI - Female fertility following dose-adjusted EPOCH-R chemotherapy in primary mediastinal B-cell lymphomas. AB - We assessed fertility/gonadal function in premenopausal women treated with dose adjusted EPOCH-Rituximab for untreated primary mediastinal B-cell lymphoma (PMBL). Eligible patents were <= 50 years and premenopausal. Serial reproductive histories were obtained and hormonal assays were performed on serum samples before, at the end of treatment and 4-18 months later. Twenty-eight eligible women had a median age (range) of 31 (21-50) years and were followed a median of 7.3 years. Of 23 patients who completed a questionnaire, 19 (83%) were and four were not menstruating prior to chemotherapy. Amenorrhea developed in 12 patients during chemotherapy. At > 1-year follow-up, 14/19 (74%) patients were menstruating, all < 35 years old, and six (43%) of these patients delivered healthy children. Hormonal assays showed ovarian dysfunction during chemotherapy in all patients with varying recovery at 4-18 months after treatment. Fertility was preserved in most women with ovarian failure confined to patients > 40 years old. PMID- 27183888 TI - A comparative study of two closed reduction methods for pediatric supracondylar humeral fractures. AB - BACKGROUND: No randomized controlled studies have confirmed the advantages of the joystick technique over the traditional manual traction. The objective of this study was to compare the results of the joystick technique and the traditional manual traction for facilitating closed reduction of pediatric supracondylar humeral fractures. METHODS: From February 2009 to December 2012, sixty eight children were included in this study. Group A included 34 fractures reduced by the joystick technique. Group B consisted of 34 fractures reduced by the traditional manual traction. Preoperative demographic data were comparable between the two groups. The operative time, fluoroscopy time, hospitalization time, time to bone union, complications were recorded in both groups. Radiologic and functional results were assessed using the Flynn scoring system. RESULTS: Closed reduction was successfully done in all the fractures of Group A while traditional closed manipulation was successfully done in 25 fractures of Group B and 9 fractures failed. There was a significant difference between the two groups in the rate of failed closed reduction (P = 0.004). The mean operative time was 30.5 +/- 9.0 and 48.2 +/- 16.4 min, and the mean fluoroscopy time was 25.4 +/- 10.5 s and 55.0 +/- 21.2 s in Group A and Group B, respectively. Both the operative time and fluoroscopy time were significantly longer in Group B (P < 0.001 and 0.001, respectively). However, there was no significant difference in terms of the mean hospitalization time, mean union time, total complications, the Flynn scores between the two groups (P > 0.05). CONCLUSIONS: The joystick technique should be chosen to facilitate closed reduction if traditional manual traction failed to yield an acceptable reduction. PMID- 27183889 TI - In vitro implant-bone interface pressure measurements for a cementless femoral implant. A preliminary study. AB - PURPOSE: Implants endurance as well as a good clinical tolerance depends on the recovery of a physiological stress distribution within bone after implantation. The purpose of the present work was to develop an alternative technique using Force Sensing Resistors (FSR) to gather in vitro pressure values at the implant bone interface for a cementless implant. METHOD: Eight cementless femoral stems were instrumented with six calibrated FSR bonded on each facet and then implanted in eight cadaver femurs. Compression tests were performed until failure and FSR pressure values were recorded. RESULTS: The average failure load was 4241 N. The maximum contact pressure measured with the FSR averaged 1.965 MPa. CONCLUSION: FSR reached many of the requirements for an ideal implant-bone interfacial sensor. This experimentation provided in vitro quantitative data on contact pressure at the implant-bone interface, which could help understanding stress shielding phenomenon and developing relevant numerical model. PMID- 27183886 TI - Increasing cumulative exposure to volatile anesthetic agents is associated with poorer neurodevelopmental outcomes in children with hypoplastic left heart syndrome. AB - OBJECTIVES: Despite improved survival in children with hypoplastic left heart syndrome (HLHS), significant concern persists regarding their neurodevelopmental (ND) outcomes. Previous studies have identified patient factors, such as prematurity and genetic syndromes, to be associated with worse ND outcomes. However, no consistent relationships have been identified among modifiable management factors, including cardiopulmonary bypass strategies, and ND outcomes after cardiac surgery in infancy. Studies in immature animals, including primates, have demonstrated neurodegeneration and apoptosis in the brain after certain levels and extended durations of anesthetic exposure. Retrospective human studies have also suggested relationships between adverse ND effects and anesthetic exposure. METHODS: Cumulative minimum alveolar concentration hours (MAC-hrs) of exposure to volatile anesthetic agents (VAA) (desflurane, halothane, isoflurane, and sevoflurane) were collected from an anesthetic database and medical record review for 96 patients with HLHS or variants. ND testing was performed between ages 4 and 5 years, including full-scale IQ, verbal IQ, performance IQ, and processing speed. Four generalized linear modes were hypothesized a priori and tested using a Gaussian (normal) distribution with an identity link. RESULTS: Cumulative VAA exposure ranged from 0 to 35.3 MAC-hrs (median 7.5 hours). Using specified covariates identified previously as significant predictors of ND outcomes, statistically significant relationships were identified between total MAC-hrs exposure and worse full-scale IQ and verbal IQ scores (P's < .05) alone and after adjusting for relevant covariates. CONCLUSIONS: Increased cumulative MAC-hrs exposure to VAA is associated with worse ND outcomes in certain domains in children with HLHS and variants. PMID- 27183891 TI - Magnetic resonance imaging and diffusion-weighted imaging findings in posterior spinal cord infarction: Case report. PMID- 27183890 TI - Characteristics of ossification of the spinal ligament; incidence of ossification of the ligamentum flavum in patients with cervical ossification of the posterior longitudinal ligament - Analysis of the whole spine using multidetector CT. AB - BACKGROUND: Ossification of the posterior longitudinal ligament (OPLL) and ossification of the ligamentum flavum (OLF) are characterized by replacement of ligamentous tissue by ectopic new bone formation. Although the background of both diseases might be similar, there are some differences between two diseases. Some patients have both OPLL and OLF. However, the incidence of both OPLL and OLF is still unclear and the precise lesions have not been investigated, yet. This study was conducted to evaluate OLF of the whole spine in patients with cervical OPLL and to analyze the relationship of the ossified lesions between OLF and OPLL. METHODS: One hundred seventy eight patients who were diagnosed as cervical OPLL by plain radiographs were included. CT images of the whole spine were taken. Ossified lesions were checked at each level of vertebral body and intervertebral disc. The ossification index of OPLL (OPLL OS index) was determined by the sum of the levels of vertebral bodies and intervertebral discs where OPLL existed. The same index was applied for detecting the level of OLF (OLF OS index). Age, gender and OPLL characteristics were compared between the OLF(+) group, OLF was seen at any levels of the spinal canal, and the OLF(-) group, OLF was not seen. RESULTS: The most frequent level of OPLL was at C5 vertebral level and OLF was predominant at upper and lower thoracic levels. Seventeen patients (9.6%) had OPLL and OLF at the same spinal level. The averaged OPLL OS index of the total spine in these patients was 8.7 +/- 6.1, ranged from 1 to 36. The averaged OLF OS index of the total spine was 3.1 +/- 2.2 (ranged from 1 to 13) in the patients who had OLF at any levels of the whole spine. One hundred fifteen patients (64.6%) with cervical OPLL had OLF at any levels of the whole spine. No relationship was found between the OPLL OS index and the OLF OS index. There was no significant difference among the data between the OLF(+) group and the OLF(-) group. CONCLUSIONS: This study demonstrated 64.6% of the patients with cervical OPLL had OLF, mainly in the thoracic spine. However, there was no relationship regarding the severity of the ossified lesions between OPLL and OLF. CT analysis of the whole spine should be carried out for the early detection of OPLL and OLF in patients with cervical OPLL. PMID- 27183892 TI - How a Surface Nanodroplet Sits on the Rim of a Microcap. AB - The location and morphology of femtoliter nanodroplets that nucleate and grow on a microcap-decorated substrate in contact with a liquid phase were investigated. We experimentally examined four different wetting combinations of the flat area and the microcaps. The results show that depending on the relative wettability, the droplets sit either on the plain surface or on the top of the microcap or on the rim of the microcap. The contact angle and, for the last case, the radial positions of the nanodroplets relative to the microcap center were characterized, in reasonable agreement with our theoretical analysis, which is based on an interfacial energy minimization argument. However, the experimental data show considerable scatter around the theoretical equilibrium curves, reflecting pinning and thus nonequilibrium effects. We also provide the theoretical phase diagram in parameter space of the contact angles, revealing under which conditions the nanodroplet will nucleate on the rim of the microcap. PMID- 27183893 TI - Enolate-mediated 1,3-dipolar cycloaddition reaction of beta-functionalized ketones with nitrile oxides: direct access to 3,4,5-trisubstituted isoxazoles. AB - TMG-catalyzed [3 + 2] organocatalytic 1,3-dipolar cycloaddition reactions of beta functionalized ketones with nitrile oxides have been developed. This strategy could generate 3,4,5-trisubstituted isoxazoles in high yields and regioselectivities. PMID- 27183894 TI - Prevalence of RHD alleles in Japanese individuals with weak D phenotype: Identification of 20 new RHD alleles. AB - We identified 46 different RHD alleles from 226 Japanese individuals with weak D phenotype, 26 of which had been previously described and 20 that were novel. Among these weak D individuals, the alleles with c.960G>A, c.845G>A (RHD*15) or c.1013T>C (RHD*01W.24) mutations were most prevalent with relative occurrences of 36.7%, 15.9% and 9.7%, respectively. These findings demonstrate that the prevalence of common weak D alleles in the Japanese population significantly differs from that of Caucasian populations. PMID- 27183895 TI - Metagenomic Insights into Transferable Antibiotic Resistance in Oral Bacteria. AB - Antibiotic resistance is considered one of the greatest threats to global public health. Resistance is often conferred by the presence of antibiotic resistance genes (ARGs), which are readily found in the oral microbiome. In-depth genetic analyses of the oral microbiome through metagenomic techniques reveal a broad distribution of ARGs (including novel ARGs) in individuals not recently exposed to antibiotics, including humans in isolated indigenous populations. This has resulted in a paradigm shift from focusing on the carriage of antibiotic resistance in pathogenic bacteria to a broader concept of an oral resistome, which includes all resistance genes in the microbiome. Metagenomics is beginning to demonstrate the role of the oral resistome and horizontal gene transfer within and between commensals in the absence of selective pressure, such as an antibiotic. At the chairside, metagenomic data reinforce our need to adhere to current antibiotic guidelines to minimize the spread of resistance, as such data reveal the extent of ARGs without exposure to antimicrobials and the ecologic changes created in the oral microbiome by even a single dose of antibiotics. The aim of this review is to discuss the role of metagenomics in the investigation of the oral resistome, including the transmission of antibiotic resistance in the oral microbiome. Future perspectives, including clinical implications of the findings from metagenomic investigations of oral ARGs, are also considered. PMID- 27183896 TI - Beyond complications: Comparison of procedural differences and diagnostic success between nurse practitioners and radiologists performing image-guided renal biopsies. AB - PURPOSE: Radiology-trained nurse practitioners (NPs) may perform image-guided medical renal biopsies with computed tomography (CT). This study evaluates the procedural differences and diagnostic success between biopsies performed by NPs compared to radiologists. DATA SOURCES: A retrospective study was performed on patients who underwent nontargeted, CT-guided renal biopsy between 2009 and 2014. Provider type (NP or radiologist), number of core specimens obtained, sedation medication dose, CT dose index (CTDI), and diagnostic success were recorded. Categorical and continuous variables were analyzed using chi2 and Student's two tailed t-test, respectively, comparing NPs with radiologists. CONCLUSIONS: A total of 386 patients were included; radiologists performed 215 biopsies and NPs performed 171 biopsies. There was no significant difference in diagnostic success, amount of tissue harvested (number of cores), radiation dose, or sedation dosage between NPs and radiologists performing CT-guided renal biopsies. Only 4% were nondiagnostic (n = 7, radiologists; n = 9, NPs; p = .325). Overall mean number of cores obtained was 3.7, mean CTDI was 176.5 mGy, mean fentanyl dose was 86.3 MUg, and mean midazolam was dose 1.54 mg without a statistically significant difference between provider types. IMPLICATIONS FOR PRACTICE: NPs perform image-guided medical renal biopsies in a similar fashion to radiologists with respect to diagnostic success, amount of tissue harvested, total radiation dose exposure, and administration of sedation. PMID- 27183897 TI - Transapical Endovascular Repair of an Ascending Aortic Pseudoaneurysm. AB - Proximal aortic pathology provides a technical challenge for endovascular repair. We present a case of successful transapical endovascular aortic repair in a patient with a proximal suture line pseudoaneurysm who was not a candidate for open surgical repair. doi: 10.1111/jocs.12766 (J Card Surg 2016;31:456-460). PMID- 27183898 TI - Qualitative and quantitative analysis of the chemical constituents in Mahuang Fuzi-Xixin decoction based on high performance liquid chromatography combined with time-of-flight mass spectrometry and triple quadrupole mass spectrometers. AB - High-performance liquid chromatography coupled with time-of-flight mass spectrometry (HPLC-TOF/MS) and high-performance liquid chromatography-triple quadrupole mass spectrometry (HPLC-QQQ/MS/MS) were utilized to clarify the chemical constituents of Mahuang-Fuzi-Xixin Decoction. There are 52 compounds, including alkaloids, amino acids and organic acids were identified or tentatively characterized by their characteristic high resolution mass data by HPLC QQQ/MS/MS. In the subsequent quantitative analysis, 10 constituents, including methyl ephedrine, aconine, songrine, fuziline, neoline, talatisamine, chasmanine, benzoylmesaconine, benzoylaconine and benzoylhypaconine were simultaneously determined by HPLC-QQQ/MS/MS with multiple reaction monitoring mode. Satisfactory linearity was achieved with wide linear range and fine determination coefficient (r > 0.9992). The relative standard deviations (RSD) of inter- and intra-day precisions were <3%. This method was also validated by repeatability, stability and recovery with RSD <3% respectively. A highly sensitive and efficient method was established for chemical constituents studying, including identification and quantification of Mahuang-Fuzi-Xixin decoction. PMID- 27183899 TI - The effect of molar pregnancies on platelet parameters. AB - The aim of this study was to compare platelet parameters between abortus groups with gestational trophoblastic disease (GTD) (molar pregnancy, invasive mole, choriocarcinoma, etc) and without disease according to pathological result. The study population consisted of patients with GTD (n = 53) and aborted patients without disease as a control group (n = 53) who were seen in our clinic between January 2010 and December 2013. In this retrospective study, age, gravidity, levels of haemoglobin, white blood cell count, platelets, platelet parameters (mean platelet volume (MPV), platelet distrubition width (PDW), platelet crit (PCT), which shows platelet functions were recorded. The pathological diagnosis of GTD was recorded. The mean platelet count, MPV, PDW and PCT levels were similar between the groups. There is no statistically significiant difference between types of GTN in these parameters according to pathological diagnosis. According to our study results, platelet count and levels of MPV, PDW ve PCT in GTD patients were similar to aborted patients without disease. PMID- 27183900 TI - Evidence generation from healthcare databases: recommendations for managing change. AB - There is an increasing reliance on databases of healthcare records for pharmacoepidemiology and other medical research, and such resources are often accessed over a long period of time so it is vital to consider the impact of changes in data, access methodology and the environment. The authors discuss change in communication and management, and provide a checklist of issues to consider for both database providers and users. The scope of the paper is database research, and changes are considered in relation to the three main components of database research: the data content itself, how it is accessed, and the support and tools needed to use the database. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27183901 TI - Adult attention-deficit hyperactivity disorder: key conceptual issues. AB - For many years, attention-deficit hyperactivity disorder (ADHD) was thought to be a childhood-onset disorder that has a limited effect on adult psychopathology. However, the symptoms and impairments that define ADHD often affect the adult population, with similar responses to drugs such as methylphenidate, dexamphetamine, and atomoxetine, and psychosocial interventions, to those seen in children and adolescents. As a result, awareness of ADHD in adults has rapidly increased and new clinical practice has emerged across the world. Despite this progress, treatment of adult ADHD in Europe and many other regions of the world is not yet common practice, and diagnostic services are often unavailable or restricted to a few specialist centres. This situation is remarkable given the strong evidence base for safe and effective treatments. Here we address some of the key conceptual issues surrounding the diagnosis of ADHD relevant to practising health-care professionals working with adult populations. We conclude that ADHD should be recognised in the same way as other common adult mental health disorders, and that failure to recognise and treat ADHD is detrimental to the wellbeing of many patients seeking help for common mental health problems. PMID- 27183903 TI - Structure of USP7 catalytic domain and three Ubl-domains reveals a connector alpha-helix with regulatory role. AB - Ubiquitin conjugation is an important signal in cellular pathways, changing the fate of a target protein, by degradation, relocalisation or complex formation. These signals are balanced by deubiquitinating enzymes (DUBs), which antagonize ubiquitination of specific protein substrates. Because ubiquitination pathways are critically important, DUB activity is often carefully controlled. USP7 is a highly abundant DUB with numerous targets that plays complex roles in diverse pathways, including DNA regulation, p53 stress response and endosomal protein recycling. Full-length USP7 switches between an inactive and an active state, tuned by the positioning of 5 Ubl folds in the C-terminal HUBL domain. The active state requires interaction between the last two Ubls (USP7(45)) and the catalytic domain (USP7(CD)), and this can be promoted by allosteric interaction from the first 3 Ubl domains of USP7 (USP7(123)) interacting with GMPS. Here we study the transition between USP7 states. We provide a crystal structure of USP7(CD123) and show that CD and Ubl123 are connected via an extended charged alpha helix. Mutational analysis is used to determine whether the charge and rigidity of this 'connector helix' are important for full USP7 activity. PMID- 27183904 TI - Detailed spectroscopic study of the role of Br and Sr in coloured parts of the Callinectes sapidus crab claw. AB - The exoskeleton of crustaceans consists mainly of calcium carbonate (CaCO3) minerals and in many cases exhibits vivid colouration due to the presence of proteins rich in carotenoid chromophores. The exposure of aquatic animals in sea water results often in the incorporation of trace elements in their exoskeleton. The bonding configuration of Br and Sr trace elements in regions with different staining (white, orange and blue) of the exoskeleton of the Callinectes sapidus in crab claw are systematically investigated by a number of complementary spectroscopic techniques, including X-ray absorption fine structure spectroscopy (EXAFS), X-ray fluorescence, Raman and visible light reflectivity spectroscopies. It is found that Sr substitutes for Ca and the Sr/Ca ratio is constant along the claw. In the orange region that includes the claw fingers, CaCO3 adopts a calcite like structure, whereas in the blue and white regions, located in the palm of the claw, an aragonite-like structure dominates. On the other hand, Br, present only in the blue and orange stained parts of the claw, is bound to phenyl and/or phenol rings of amino acid residues, most probably to phenylalanine and/or tyrosine, of the chromophore protein. PMID- 27183902 TI - Moving towards causality in attention-deficit hyperactivity disorder: overview of neural and genetic mechanisms. AB - Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by developmentally inappropriate levels of inattention and hyperactivity or impulsivity. The heterogeneity of its clinical manifestations and the differential responses to treatment and varied prognoses have long suggested myriad underlying causes. Over the past decade, clinical and basic research efforts have uncovered many behavioural and neurobiological alterations associated with ADHD, from genes to higher order neural networks. Here, we review the neurobiology of ADHD by focusing on neural circuits implicated in the disorder and discuss how abnormalities in circuitry relate to symptom presentation and treatment. We summarise the literature on genetic variants that are potentially related to the development of ADHD, and how these, in turn, might affect circuit function and relevant behaviours. Whether these underlying neurobiological factors are causally related to symptom presentation remains unresolved. Therefore, we assess efforts aimed at disentangling issues of causality, and showcase the shifting research landscape towards endophenotype refinement in clinical and preclinical settings. Furthermore, we review approaches being developed to understand the neurobiological underpinnings of this complex disorder, including the use of animal models, neuromodulation, and pharmacoimaging studies. PMID- 27183905 TI - Functional cooperation between KCa3.1 and TRPC1 channels in human breast cancer: Role in cell proliferation and patient prognosis. AB - Intracellular Ca2+ levels are important regulators of cell cycle and proliferation. We, and others, have previously reported the role of KCa3.1 (KCNN4) channels in regulating the membrane potential and the Ca2+ entry in association with cell proliferation. However, the relevance of KC3.1 channels in cancer prognosis as well as the molecular mechanism of Ca2+ entry triggered by their activation remain undetermined. Here, we show that RNAi-mediated knockdown of KCa3.1 and/or TRPC1 leads to a significant decrease in cell proliferation due to cell cycle arrest in the G1 phase. These results are consistent with the observed upregulation of both channels in synchronized cells at the end of G1 phase. Additionally, knockdown of TRPC1 suppressed the Ca2+ entry induced by 1 EBIO-mediated KCa3.1 activation, suggesting a functional cooperation between TRPC1 and KCa3.1 in the regulation of Ca2+ entry, possibly within lipid raft microdomains where these two channels seem to co-localize. We also show significant correlations between KCa3.1 mRNA expression and poor patient prognosis and unfavorable clinical breast cancer parameters by mining large datasets in the public domain. Together, these results highlight the importance of KCa3.1 in regulating the proliferative mechanisms in breast cancer cells as well as in providing a promising novel target in prognosis and therapy. PMID- 27183906 TI - Selection and characterization of DNA aptamer for metastatic prostate cancer recognition and tissue imaging. AB - Prostate cancer (PCa) is the second leading cause of death and most prevalent cancer in men. The absence of curative options for castration-resistant metastatic prostate cancer and biomarkers able to discriminate between indolent and aggressive tumors contribute to these statistics. In this study, a DNA aptamer termed DML-7 was successfully selected against human PCa cell line DU145 by using the cell-based systematic evolution of ligands by exponential enrichment (SELEX) method. The selected aptamer DML-7 was found to internalize into target cells in a temperature-dependent manner and exhibit high binding affinity for target cells with dissociation constants in the nanomolar range. Binding analysis further revealed that DML-7 only binds to DU145 and PC-3 cells with metastatic potential, but not to LNCaP or 22Rv1 cells with low or nonmetastatic potential, demonstrating that DML-7 has excellent selectivity for the recognition of the metastatic PCa cells. Clinical tissue imaging further confirmed these results. Therefore, both high binding affinity and specificity to metastatic PCa cells and tissues afford DML-7 with the potential for development into a novel tool for diagnosis and targeted drug delivery against metastatic prostate cancer. PMID- 27183907 TI - Combining 2-deoxy-D-glucose with fenofibrate leads to tumor cell death mediated by simultaneous induction of energy and ER stress. AB - Unregulated growth and replication as well as an abnormal microenvironment, leads to elevated levels of stress which is a common trait of cancer. By inducing both energy and endoplasmic reticulum (ER) stress, 2-Deoxy-glucose (2-DG) is particularly well-suited to take advantage of the therapeutic window that heightened stress in tumors provides. Under hypoxia, blocking glycolysis with 2 DG leads to significant lowering of ATP resulting in energy stress and cell death in numerous carcinoma cell types. In contrast, under normoxia, 2-DG at a low concentration is not toxic in most carcinomas tested, but induces growth inhibition, which is primarily due to ER stress. Here we find a synergistic toxic effect in several tumor cell lines in vitro combining 2-DG with fenofibrate (FF), a drug that has been safely used for over 40 years to lower cholesterol in patients. This combination induces much greater energy stress than either agent alone, as measured by ATP reduction, increased p-AMPK and downregulation of mTOR. Inhibition of mTOR results in blockage of GRP78 a critical component of the unfolded protein response which we speculate leads to greater ER stress as observed by increased p-eIF2alpha. Moreover, to avoid an insulin response and adsorption by the liver, 2-DG is delivered by slow-release pump yielding significant anti-tumor control when combined with FF. Our results provide promise for developing this combination clinically and others that combine 2-DG with agents that act synergistically to selectively increase energy and ER stress to a level that is toxic to numerous tumor cell types. PMID- 27183908 TI - ISL1, a novel regulator of CCNB1, CCNB2 and c-MYC genes, promotes gastric cancer cell proliferation and tumor growth. AB - Islet-1 (ISL1) belongs to the LIM homeodomain transcription factor family, which is specifically expressed in certain tissue types only. Previously, we reported that ISL1 is aberrantly overexpressed in gastric cancer (GC). However, its role in GC is not clear. Here, we report that ISL1 is aberrantly upregulated not only in human gastric carcinoma tissues but also in some GC cell lines. Upregulated ISL1 expression enhanced xenografted gastric carcinoma development, while ISL1 knockdown inhibited GC growth in nude mice. ISL1 overexpression promoted GC cell proliferation, colony formation, and cell growth in soft agar, and facilitated cell cycle transition in GC cells, demonstrated an increase in the proportion of cells in the G2/M and S phases and a decrease in the proportion of cells in the G1 phase. Furthermore, we provide evidence that ISL1 is a novel regulator of the cyclin B1 (CCNB1), cyclin B2 (CCNB2) and c-myc (c-MYC) genes. ISL1 activated the expression of these genes in GC cells by binding to the conserved binding sites on their promoters or enhancers. The expression levels of the genes were decreased in response to ISL1 knockdown. Therefore, ISL1 may serve as a potential therapeutic target in GC. PMID- 27183909 TI - A comparison of R-EPOCH and R-CHOP as a first-line regimen in de novo DLBCL patients with high Ki-67 expression in a single institution. AB - Diffuse large B-cell lymphoma (DLBCL) patients with high Ki-67 expression receive limited benefits from R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapy. This study aims to compare the R-EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) and R CHOP regimens as first-line therapy in DLBCL patients with high Ki-67 expression. Data from 44 untreated DLBCL patients with high Ki-67 expression receiving R EPOCH therapy were matched with those from 132 untreated DLBCL patients with high Ki-67 expression receiving R-CHOP therapy based on the International Prognostic Index (IPI: age, Ann Arbor stage, performance status, LDH level, number of extranodal sites), gender, and Ki-67 expression. In the R-EPOCH group, 42/44 patients were eligible for response evaluation. A total of 35 patients (83.3%) achieved complete remission (CR); 6 patients (14.3%) achieved partial remission (PR); and one patient (2.4%) exhibited progressive disease (PD) after 2 cycles of therapy. Patients in the R-EPOCH group presented better survival outcomes than those in the R-CHOP group (3-year overall survival [OS]: 89.9% vs. 70.2%, p = 0.041; 3-year progression-free survival [PFS]: 86.6% vs. 59.7%, p = 0.024). The survival superiority of the R-EPOCH over the R-CHOP regimen persisted when considering only patients of low-to-intermediate IPI risk, but it was not observed in those of high IPI risk. Our data suggest that R-EPOCH could be superior to R-CHOP as a first-line regimen in DLBCL patients with high Ki-67 expression, especially in those of low-to-intermediate IPI risk. PMID- 27183911 TI - Nuclear delivery of recombinant OCT4 by chitosan nanoparticles for transgene-free generation of protein-induced pluripotent stem cells. AB - Protein-based reprogramming of somatic cells is a non-genetic approach for the generation of induced pluripotent stem cells (iPSCs), whereby reprogramming factors, such as OCT4, SOX2, KLF4 and c-MYC, are delivered as functional proteins. The technique is considered safer than transgenic methods, but, unfortunately, most protein-based protocols provide very low reprogramming efficiencies. In this study, we developed exemplarily a nanoparticle (NP)-based delivery system for the reprogramming factor OCT4. To this end, we expressed human OCT4 in Sf9 insect cells using a baculoviral expression system. Recombinant OCT4 showed nuclear localization in Sf9 cells indicating proper protein folding. In comparison to soluble OCT4 protein, encapsulation of OCT4 in nuclear-targeted chitosan NPs strongly stabilized its DNA-binding activity even under cell culture conditions. OCT4-loaded NPs enabled cell treatment with high micromolar concentrations of OCT4 and successfully delivered active OCT4 into human fibroblasts. Chitosan NPs therefore provide a promising tool for the generation of transgene-free iPSCs. PMID- 27183910 TI - NOTCH blockade combined with radiation therapy and temozolomide prolongs survival of orthotopic glioblastoma. AB - Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. The current standard of care includes surgery followed by radiotherapy (RT) and chemotherapy with temozolomide (TMZ). Treatment often fails due to the radiation resistance and intrinsic or acquired TMZ resistance of a small percentage of cells with stem cell-like behavior (CSC). The NOTCH signaling pathway is expressed and active in human glioblastoma and NOTCH inhibitors attenuate tumor growth in vivo in xenograft models. Here we show using an image guided micro-CT and precision radiotherapy platform that a combination of the clinically approved NOTCH/gamma-secretase inhibitor (GSI) RO4929097 with standard of care (TMZ + RT) reduces tumor growth and prolongs survival compared to dual combinations. We show that GSI in combination with RT and TMZ attenuates proliferation, decreases 3D spheroid growth and results into a marked reduction in clonogenic survival in primary and established glioma cell lines. We found that the glioma stem cell marker CD133, SOX2 and Nestin were reduced following combination treatments and NOTCH inhibitors albeit in a different manner. These findings indicate that NOTCH inhibition combined with standard of care treatment has an anti-glioma stem cell effect which provides an improved survival benefit for GBM and encourages further translational and clinical studies. PMID- 27183912 TI - Translin and Trax differentially regulate telomere-associated transcript homeostasis. AB - Translin and Trax proteins are highly conserved nucleic acid binding proteins that have been implicated in RNA regulation in a range of biological processes including tRNA processing, RNA interference, microRNA degradation during oncogenesis, spermatogenesis and neuronal regulation. Here, we explore the function of this paralogue pair of proteins in the fission yeast. Using transcript analysis we demonstrate a reciprocal mechanism for control of telomere associated transcripts. Mutation of tfx1+ (Trax) elevates transcript levels from silenced sub-telomeric regions of the genome, but not other silenced regions, such as the peri-centromeric heterochromatin. In the case of some sub-telomeric transcripts, but not all, this elevation is dependent on the Trax paralogue, Tsn1 (Translin). In a reciprocal fashion, Tsn1 (Translin) serves to repress levels of transcripts (TERRAs) from the telomeric repeats, whereas Tfx1 serves to maintain these elevated levels. This reveals a novel mechanism for the regulation of telomeric transcripts. We extend this to demonstrate that human Translin and Trax also control telomere-associated transcript levels in human cells in a telomere specific fashion. PMID- 27183913 TI - Fine-mapping markers of lung cancer susceptibility in a sub-region of chromosome 19q13.3 among Chinese. AB - Linkage disequilibrium-mapping studies in Caucasians have indicated anassociation of Chr19q13.3 sub-region spanning ERCC2, PPP1R13L, CD3EAP and ERCC1 with several cancers. To refine the region of association and identify potential causal variations among Asians, we performed a fine-mapping study using 32 (39) SNPs in a 71.654kb sub-region. The study included 384 Chinese lung cancer cases and 387 controls. Seven closely situated SNPs showed significant associations with lung cancer risk in five different genetic models of single-locus associations (adjusted for smoking duration). These were PPP1R13L rs1970764 [OR (95% CI) = 1.58 (1.09-2.29), P = 0.014] in a recessive model and PPP1R13L rs1005165 [OR (95% CI) = 1.25 (1.01-1.54), P = 0.036], CD3EAP rs967591 [OR (95% CI) = 1.40 (1.13 1.75), P = 0.0023], rs735482 [OR (95% CI) = 1.29 (1.03-1.61), P = 0.026], rs1007616 [OR (95% CI) = 0.78 (0.61-1.00), P = 0.046], and rs62109563 [OR (95% CI) = 1.28 (1.03-1.59), P = 0.024] in a log-additive model and ERCC1 rs3212965 [OR (95% CI) = 0.70 (0.52-0.94), P = 0.019] in an over-dominant model. Six haplotype blocks were determined in the sub-region. Using an alternative approach where we performed a haplotype analysis of all significant polymorphisms, rs1970764 was found to be most consistently associated with lung cancer risk. The combined data suggest that the sub-region with the strongest association to lung cancer susceptibility might locate to the 23.173kb from PPP1R13L intron8 rs1970764 to rs62109563 3' to CD3EAP. Limited risk loci and span on lung cancer in this sub-region are initially defined among Asians. PMID- 27183915 TI - Absorbable polymeric surgical clips for appendicular stump closure: A randomized control trial of laparoscopic appendectomy with lapro-clips. AB - A randomized control trial was performed to evaluate the effectiveness and safety of absorbable polymeric clips for appendicular stump closure in laparoscopic appendectomy (LA). Patients were randomly enrolled into an experimental group (ligation of the appendicular base with Lapro-Clips, L-C group) or control group (ligation of the appendicular base with Hem-o-lok Clips, H-C group). We identified 1,100 patients who underwent LA between April 1, 2012 and February 3, 2015. Overall, 99 patients (9.0%, 99/1,100) developed a complication following LA (47 [8.5%] in the L-C group and 52 [9.5%] in the H-C group (P = 0.598). No statistically significant differences were observed in intra-abdominal abscesses, stump leakage, superficial wound infections, post-operative abdominal pain, overall adverse events, or the duration of the operations and hospital stays between the groups (all p > 0.05). Adverse risk factors associated with the use of absorbable clips in LA included body mass index >= 27.5 kg/m2, diabetes, American Society of Anesthesiologists degree >= III, gangrenous appendicitis, severe inflammation of the appendix base, appendix perforation, and the absence of peritoneal drainage. The results indicate that the Lapro-Clip is a safe and effective device for closing the appendicular stump in LA in select patients with appendicitis. PMID- 27183916 TI - Concurrent cisplatin and 5-fluorouracil versus concurrent cisplatin and docetaxel with radiotherapy for esophageal squamous cell carcinoma: a propensity score matched analysis. AB - The optimal concurrent chemotherapy regimen with radiotherapy for esophageal cancer is unknown. Here, we compared the survival outcomes and toxicity of definitive chemoradiotherapy with either cisplatin/5-fluorouracil (PF) or docetaxel/cisplatin (DP) in patients with unresectable esophageal squamous cell carcinoma (ESCC). In this study, we identified 317 patients with ESCC who received PF or DP concurrently with definitive radiotherapy. PF group patients received two cycles of cisplatin (60 mg/m2) and 5-fluorouracil (300 mg/m2) at 4 week intervals during radiotherapy. DP group patients received a concurrent three weekly schedule of docetaxel (60 mg/m2) and cisplatin (80 mg/m2) or cisplatin (25 mg/m2) and docetaxel (25 mg/m2) weekly. The overall survival (OS) and progression free survival (PFS) were compared using propensity score (-adjusted, -weighted, stratified, and -matched) analyses. A sensitivity analysis was performed to examine the impact of unmeasured confounders. Inverse probability of treatment weighting for propensity score demonstrated an improvement in OS and PFS with DP group in comparison with PF group (hazard ratio, 0.700; 95% CI, 0.577-0.851) and similar results were achieved with propensity score matching and stratification. Grade 3-4 esophagitis was more common (16/102 vs. 4/102) and grade 3-4 thrombopenia and skin toxicity were less common (3/102 vs. 10/102; 7/102 vs. 19/102; respectively) in the PF group than the DP group. In conclusion, concurrent chemoradiotherapy with the DP regimen resulted in better OS and PFS compared to concurrent PF regimen with tolerable toxicities in ESCC patients. Prospective randomized trials are required to confirm the efficacy of the DP regimen. PMID- 27183914 TI - Physiological and pathological implications of 5-hydroxymethylcytosine in diseases. AB - Gene expression is the prerequisite of proteins. Diverse stimuli result in alteration of gene expression profile by base substitution for quite a long time. However, during the past decades, accumulating studies proved that bases modification is involved in this process. CpG islands (CGIs) are DNA fragments enriched in CpG repeats which mostly locate in promoters. They are frequently modified, methylated in most conditions, thereby suggesting a role of methylation in profiling gene expression. DNA methylation occurs in many conditions, such as cancer, embryogenesis, nervous system diseases etc. Recently, 5 hydroxymethylcytosine (5hmC), the product of 5-methylcytosine (5mC) demethylation, is emerging as a novel demethylation marker in many disorders. Consistently, conversion of 5mC to 5hmC has been proved in many studies. Here, we reviewed recent studies concerning demethylation via 5hmC conversion in several conditions and progress of therapeutics-associated with it in clinic. We aimed to unveil its physiological and pathological significance in diseases and to provide insight into its clinical application potential. PMID- 27183917 TI - Cooperation of Nutlin-3a and a Wip1 inhibitor to induce p53 activity. AB - Targeting the Mdm2 oncoprotein by drugs has the potential of re-establishing p53 function and tumor suppression. However, Mdm2-antagonizing drug candidates, e. g. Nutlin-3a, often fail to abolish cancer cell growth sustainably. To overcome these limitations, we inhibited Mdm2 and simultaneously a second negative regulator of p53, the phosphatase Wip1/PPM1D. When combining Nutlin-3a with the Wip1 inhibitor GSK2830371 in the treatment of p53-proficient but not p53 deficient cells, we observed enhanced phosphorylation (Ser 15) and acetylation (Lys 382) of p53, increased expression of p53 target gene products, and synergistic inhibition of cell proliferation. Surprisingly, when testing the two compounds individually, largely distinct sets of genes were induced, as revealed by deep sequencing analysis of RNA. In contrast, the combination of both drugs led to an expression signature that largely comprised that of Nutlin-3a alone. Moreover, the combination of drugs, or the combination of Nutlin-3a with Wip1 depletion by siRNA, activated p53-responsive genes to a greater extent than either of the compounds alone. Simultaneous inhibition of Mdm2 and Wip1 enhanced cell senescence and G2/M accumulation. Taken together, the inhibition of Wip1 might fortify p53-mediated tumor suppression by Mdm2 antagonists. PMID- 27183918 TI - HCV-related liver and lymphoproliferative diseases: association with polymorphisms of IL28B and TLR2. AB - To explore the relationship between innate immunity and hepatitis C Virus (HCV) in determining the risk of cirrhosis (CIR), hepatocellular carcinoma (HCC), mixed cryoglobulinemia syndrome (MCS) and non-Hodgkin lymphoma (NHL), we investigated the impact of the toll-like receptor-2 (TLR2) and interleukin-28B (IL28B) genetic variants. TLR2 -174 del variant was associated with TLR2 expression and with specific downstream molecules that drive the expression of different interleukins; rs12979860 Il28B was important in response to interferon-treatment and in spontaneous clearance of HCV. The risk for liver and lymphoproliferative diseases in HCV progression was clarified by stratifying 862 HCV-positive patients into groups based on liver (CIR, HCC) and lymphoproliferative HCV related diseases (MCS, NHL) and compared with chronic HCV (CHC) infection. Analysis of TLR2-IL28B haplotypes showed an association of wild type haplotype with the lymphoproliferative diseases (OR 1.77, p = 0.029) and a slight increase in HCV viral load (HR 1.38, p = 0.054). Wild type haplotype (TLR2 ins/ins- IL28B C/C) was also found associated with older age in patients with an hepatic diseases (in CIR and in HCC p = 0.038 and p = 0.020, respectively) supporting an effect of innate immunity in the liver disease progression. TLR2 and IL28B polymorphisms in combination showed a role in the control of HCV viral load and different HCV disease progression. PMID- 27183920 TI - Simulation of interindividual differences in inactivation of reactive para benzoquinone imine metabolites of diclofenac by glutathione S-transferases in human liver cytosol. AB - Diclofenac is a widely prescribed NSAID that causes severe idiosyncratic drug induced liver injury (IDILI) in a small part of the patient population. Formation of protein-reactive metabolites is considered to play a role in the development of diclofenac-induced IDILI. Therefore, a high hepatic activity of enzymes involved in bioactivation of diclofenac is expected to increase the risk for liver injury. However, the extent of covalent protein binding may also be determined by activity of protective enzymes, such as glutathione S-transferases (GSTs). This is supported by an association study in which a correlation was found between NSAID-induced IDILI and the combined null genotypes of GSTM1 and GSTT1. In the present study, the activity of 10 different recombinant human GSTs in inactivation of protein-reactive quinoneimine (QI) metabolites of diclofenac was tested. Both at low and high GSH concentrations, high activities of GSTA1-1, A2-2, A3-3, M1-1, M3-3 and P1-1 in the inactivation of these QIs were found. By using the expression levels of GSTs in livers of 22 donors, a 6-fold variation in GST-dependent inactivation of reactive diclofenac metabolites was predicted. Moreover, it was shown in vitro that GSTs can strongly increase the efficiency of GSH to protect against the alkylation of the model thiol N-acetylcysteine by reactive diclofenac metabolites. The results of this study demonstrate that variability of GST expression may significantly contribute to the inter individual differences in susceptibility to diclofenac-induced liver injury. In addition, expression levels of GSTs in in vitro models for hepatotoxicity may be important factors determining sensitivity to diclofenac cytotoxicity. PMID- 27183919 TI - HCV core protein binds to gC1qR to induce A20 expression and inhibit cytokine production through MAPKs and NF-kappaB signaling pathways. AB - Hepatitis C virus (HCV) infection is characterized by a strong propensity toward chronicity. During chronic HCV infection, HCV core protein is implicated in deregulating cytokine expression that associates with chronic inflammation. A20 is known as a powerful suppressor in cytokine signaling, in this study, we explored the A20 expression in macrophages induced by HCV core protein and the involved signaling pathways. Results demonstrated that HCV core protein induced A20 expression in macrophages. Silencing A20 significantly enhanced the secretion of IL-6, IL-1beta and TGF-beta1, but not IL-8 and TNF. Additionally, HCV core protein interacted with gC1qR, but not TLR2, TLR3 and TLR4 in pull-down assay. Silencing gC1qR abrogated core-induced A20 expression. Furthermore, HCV core protein activated MAPK, NF-kappaB and PI3K/AKT pathways in macrophages. Inhibition of P38, JNK and NF-kappaB but not ERK and AKT activities greatly reduced the A20 expression. In conclusion, the study suggests that HCV core protein ligates gC1qR to induce A20 expression in macrophages via P38, JNK and NF kappaB signaling pathways, which leads to a low-grade chronic inflammation during HCV infection. It represents a novel mechanism by which HCV usurps the host for persistence. PMID- 27183921 TI - Comparison of the transformation temperatures of heat-activated Nickel-Titanium orthodontic archwires by two different techniques. AB - OBJECTIVES: The purpose of this study was to investigate the suitability of the Bend and Free Recovery (BFR) method as a standard test method to determine the transformation temperatures of heat-activated Ni-Ti orthodontic archwires. This was done by determining the transformation temperatures of two brands of heat activated Ni-Ti orthodontic archwires using the both the BFR method and the standard method of Differential Scanning Calorimetry (DSC). The values obtained from the two methods were compared with each other and to the manufacturer-listed values. METHODS: Forty heat-activated Ni-Ti archwires from both Rocky Mountain Orthodontics (RMO) and Opal Orthodontics (Opal) were tested using BFR and DSC. Round (0.016 inches) and rectangular (0.019*0.025 inches) archwires from each manufacturer were tested. The austenite start temperatures (As) and austenite finish temperatures (Af) were recorded. RESULTS: For four of the eight test groups, the BFR method resulted in lower standard deviations than the DSC method, and, overall, the average standard deviation for BFR testing was slightly lower than for DSC testing. Statistically significant differences were seen between the transformation temperatures obtained from the BFR and DSC test methods. However, the Af temperatures obtained from the two methods were remarkably similar with the mean differences ranging from 0.0 to 2.1 degrees C: Af Opal round (BFR 26.7 degrees C, DSC 27.6 degrees C) and rectangular (BFR 27.6 degrees C, DSC 28.6 degrees C); Af RMO round (BFR 25.5 degrees C, DSC 25.5 degrees C) and rectangular (BFR 28.0 degrees C, DSC 25.9 degrees C). Significant differences were observed between the manufacturer-listed transformation temperatures and those obtained with BFR and DSC testing for both manufacturers. SIGNIFICANCE: The results of this study suggest that the Bend and Free Recovery method is suitable as a standard method to evaluate the transformation temperatures of heat-activated Ni Ti orthodontic archwires. PMID- 27183922 TI - The time course of endogenous erythropoietin, IL-6, and TNFalpha in response to acute hypoxic exposures. AB - Erythropoietin (EPO) rapidly decreases on return to sea level (SL) after chronic altitude exposure. Acute hypoxia may provide an additional stimulus to prevent the decline in EPO. Proinflammatory cytokines, interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFalpha) have been shown to inhibit EPO production. Optimal normobaric hypoxic exposure has not been established; therefore, investigation of methods eliciting the greatest response in EPO to limit physiological stress is required. Eight men (age 27 +/- 4 years, body mass 77.5 +/- 9.0 kg, height 179 +/- 6 cm) performed four passive exposures to different normobaric hypoxic severities [FiO2 : 0.209 (SL), FiO2 : ~0.135 (3600 m), FiO2 : ~0.125 (4200 m) and FiO2 : ~0.115 (4800 m)] in a hypoxic chamber for 2 h. Venous blood was drawn pre-exposure and then at 1, 2, 4, 6, and 8 h to determine EPO concentration ([EPO]), IL-6, and TNFalpha. During 4200 and 4800 m, [EPO] increased from 5.9 +/- 1.5 to 8.1 +/- 1.5 mU/mL (P = 0.009) and 6.0 +/- 1.4 to 8.9 +/- 2.0 mU/mL (P = 0.037), respectively, with [EPO] increase peaking at 4 h (2 h post-exposure). There were no differences in IL-6 or TNFalpha during or post exposure. Increased [EPO] was found 2 h post hypoxic exposure as result of 2 h of normobaric hypoxia >=4200 m. There was no dose-response relationship in [EPO] between simulated hypoxia severities. PMID- 27183923 TI - Polio: the fight of the public against a disease it does not understand with a vaccine it does not trust. PMID- 27183924 TI - Two-year survival of severe chronic obstructive pulmonary disease subjects requiring invasive mechanical ventilation and the factors affecting survival. AB - OBJECTIVE: To investigate two-year survival rates and the factors affecting survival in patients of severe chronic obstructive pulmonary disease requiring invasive mechanical ventilation. METHODS: The retrospective study was conducted at Yuzuncuy?l University, Van, Turkey, and comprised record of in-patients with moderate to severe chronic obstructive pulmonary disease who required invasive mechanical ventilation in the intensive care unit of the Pulmonary Diseases Department between January 2007 and December 2010. Correlation between survival and parameters such as age, gender, duration of illness, history of smoking, arterial blood gas values, pulmonary artery pressure, left ventricular ejection fraction, body mass index and laboratory findings were investigated. SPSS 19 was used for statistical analysis. RESULTS: Of the 69 severe COPD subjects available, 20 (29%) were excluded as they did not meet the inclusion criteria. Overall in hospital mortality rate was 42% (n:29). Of the remaining 20 (29%) who comprised the study group, 14(70%) were men and 6(30%) were women. The mortality rates at the end of 3rd, 6th, 12th and 24th months were 61%, 76%, 84% and 85.5% respectively. There was no correlation between gender and survival in time point (p>0.05). The only factor that affected the rate of mortality at the end of the 3rd month was age (p<0.05). Mortality was high in subjects with advanced ages (p<0.05). Duration of illness affected the survival at the end of the six month (p<0.05). Survival rates were high in subjects with longer illness durations (p<0.05). Haematocrit level was the only factor that affected mortality rates at the end of 12th and 24th months (p<0.05). Subjects with higher haematocrit levels had higher survival rates (p<0.05). CONCLUSIONS: Age, duration of illness and haematocrit levels were the most important factors that affected survival in chronic obstructive pulmonary disease patients requiring mechanical ventilation. PMID- 27183925 TI - Frequency and distribution of angiographically occluded coronary artery and in hospital outcome of patients with Non ST elevation myocardial infarction. AB - OBJECTIVE: To calculate the frequency and distribution of occluded coronary artery in patients with recent non-ST elevation myocardial infarction undergoing coronary angiography, and to compare major adverse cardiovascular events during hospitalisation with patients suffering from non-occluded coronary artery. METHODS: The cross-sectional analytical study was conducted at Tabba Heart Institute, Karachi, from July2013 to March 2014. Patients of both gender and all ages undergoing angiography with non-ST elevation myocardial infarction were included. Data on patient demographics, angiographic findings and in-hospital complications was collected. Frequency of occluded vessels and their distribution was reported. Multivariate logistic regression modelling was used to examine variables associated with an occluded coronary artery in non-ST elevation myocardial infarction. Major adverse cardiovascular events were compared between patients of occluded and non-occluded coronary aetery. A two sided p-value of < 0.05 was taken as significant. RESULTS: In 703 patients studied, occluded coronary artery was present in 277(39%). Predictors of having an occluded coronary artery were increasing age (57.6+/-11.2 vs. 60.0+/-10.0; p: 0.03) and low left ventricular ejection fraction (43.9+/-12.2 vs. 50.1+/-10.1; p: 0.000). There was no significant difference in terms of major adverse cardiovascular events in patients with occluded and non-occluded coronary arteries (Hazard Ratio: 0.53, 95% confidence interval: 0.14-1.98; p=0.33). CONCLUSIONS: Totally occluded coronary vessel is a frequent finding in non-ST elevation myocardial infarction, highlighting the need for angiography and re-vascularisation to salvage at-risk myocardium in selected patients. PMID- 27183926 TI - Impact of delay in admission on the outcome of critically ill patients presenting to the emergency department of a tertiary care hospital from low income country. AB - OBJECTIVE: To assess the impact of admission delay on the outcome of critical patients. METHODS: The retrospective chart review was done at Aga Khan University Hospital, Karachi, and comprised adult patients visiting the Emergency Department during 2010. Outcome measures assessed were total hospital length of stay, total cost of the visit and in-hospital mortality. Patients admitted within 6 hours of presentation at Emergency Department were defined as non-delayed. Data was analysed using SPSS 19. RESULTS: Of the 49,532 patients reporting at the Emergency Department during the study period, 17,968 (36.3%) were admitted. Of them 2356(13%) were admitted to special or intensive care units, 1595(67.7%) of this sub-group stayed in the Emergency Department for >6 hours before being shifted to intensive care. The study focussed on 325(0.65%) of the total patients; 164(50.5%) in the non-delayed group and 161(49.5%) in the delayed group. The admitting diagnosis of myocardial infarction (p=0.00) and acute coronary syndrome (p=0.01) was significantly more common in the non-delayed group compared to other diagnoses like cerebrovascular attacks (p=0.03) which was significantly more common in the delayed group. There was no significant difference in the hospital length of stay between the two groups (p>0.05). The Emergency Department cost was significantly increased in the delayed group (p<0.05), but there was no difference in the overall hospital cost between the groups (p>0.05). CONCLUSIONS: There was no significant difference in the delayed and non-delayed groups, but long Emergency Department stays are distressing for both physicians and patients. PMID- 27183927 TI - Iranian road traffic injury project: assessment of road traffic injuries in Iran in 2012. AB - OBJECTIVE: To assess the status of road traffic injuries in Iran. METHODS: The retrospective study was conducted in Iran and comprised all reported traffic accidents from March 2011 to March 2012 that were recorded in the national traffic accident database. The information collected included demographic data specific to road traffic accidents and injuries. The data was summarised and presented using frequencies and percentages. RESULTS: There were a total of 452192 road traffic accidents with 252246 victims in the one-year period. The highest number of accidents, 110348(47%), involved individuals in the 15-30 year age group. Among the gender-identified injured, 206171(78.4%) were male and 56639 (21.6%) were female. Besides, 298750(73.2%) accidents took place between 6am and 6pm. In terms of location, the province of Semnan had the highest rates of injury and death (913 per 100000 and 41per 100000, respectively), while the lowest rate of injury was in Alborz (131 per 100000) and lowest rate of death was in Tehran (5 per 100000). The majority of accidents 301516(66.7%) occurred on inner city roads. Although the total number of victims in inner city roads (180893) was higher than outer the city roads (2.2:1), the number of deaths (8615) on outer roads was higher (3:1). CONCLUSIONS: Road traffic injuries placed a heavy burden on the Iranian population, especially on young men. Comprehensive strategies and policies must be implemented for effective prevention of road accidents in Iran. PMID- 27183928 TI - Lactacyd FH as an adjuvant therapy for vulvovaginal infections in Pakistani women: FRESH study, a satisfaction survey. AB - OBJECTIVE: To demonstrate that adjuvant therapy with lactic acid+lactoserum solution provides satisfactory symptomatic relief and is safe in patients with vulvo-vaginal infections. METHODS: The open-label survey was conducted at 96 private consultation clinics in 14 cities across Pakistan from May to October 2010, and included consecutive patients >18 years of age with first/recurrent episode of vulvo-vaginal infections, having clinical signs and symptoms of such infections, receiving antibiotics for current infections. Data collected included vulvo-vaginal infection symptoms, baseline history of diabetes and hormone replacement therapy, bimanual examination, and current antibiotic treatment. Follow-up was done at 14 days. Compliance and symptomatic relief, safety (solicited reporting) was noted on day 14 or anytime during the study period. RESULTS: Overall, 919 patients were enrolled. Of these, 842(91.6%) patients completed the study. The mean age was 32.6+/-8.4 years and 295(35%) were diagnosed to have bacterial vaginosis, 278(33%) vaginal candidiasis, and 126(15%) trichomoniasis. The most commonly used antibiotic was metronidazole in 438(52%) cases. Patients used lactic acid+lactoserum for mean duration of 9.7 4.4 days, twice a day, and reported symptomatic relief by fourth day of application, as assessed by reduction in malodour in 681(80.1%) cases, itching 661(78.5%), burning sensation 652(77.4%), and pain 552(65.6%). Lactic acid+lactoserum was reported to be gentle on skin in 769(91.3%) cases, provide feeling of freshness 727(86.3%), and have mild fragrance 724(85.9%). Overall, 746(88.6%) patients reported satisfaction with lactic acid+lactoserum, and 671(79.7%) patients were willing to use it again. No adverse events were reported. CONCLUSIONS: Lactic acid+lactoserum as an adjuvant treatment of vulvo-vaginal infections demonstrated high percentage of satisfaction and safety in Pakistani women. PMID- 27183929 TI - A comparison of two techniques of preparing bone marrow aspirate slides. AB - OBJECTIVE: To compare direct smear technique with ethylenediaminetetraacetic acid (EDTA) preserved smear technique in terms of preparing bone marrow aspirate slides. METHODS: This prospective study was carried out between September 2009 and July 2012 at the Haematology/Oncology Department, King Khalid University Hospital, Riyadh, Saudi Arabia. With a standard gauge disposable bone marrow aspirate needle, 0.5 to 1.0 ml bone marrow was aspirated with a 10ml syringe. Half of the marrow was immediately transferred to an EDTA tube with gentle mixing, while slides were prepared directly from the rest of the sample in the syringe. The tube sample was used to prepare slides at the end of the procedure. A score of 1-4 was assigned to each slide depending on the quality and number of particles. RESULTS: A total of 245 bone marrow aspirate samples were evaluated related to 216 patients. Of the total, 238 (97%) samples were included in the study. The mean score for the direct smear group was 3.40+/-0.79 and for the EDTA smear group it was 3.34+/-0.75 (p=0.27), which was not statistically significant. An informal comparison of the morphological analysis of the samples did not reveal any differences. CONCLUSIONS: Bone marrow aspirate slides prepared at the end of the procedure from EDTA preserved samples were not inferior to slides prepared directly from the aspirated sample. PMID- 27183931 TI - Sub-threshold frequency doubled Nd. YAG modified mild maculr grid laser for diffuse diabetic maculopathy. AB - OBJECTIVE: To determine the anatomical and functional improvement in eyes with diffuse macular oedema after modified mild macular grid laser. METHODS: The prospective study was conducted at the Department of Ophthalmology Unit II, Civil Hospital Karachi, and the Department of Ophthalmology, Dow International Medical College, Karachi, from June 2011 to May 2014. We used neodymium-doped yttrium aluminium garnet 532nm frequency-doubled green laser to treat all eligible patients. Treatment variables were a spot size of 50 microns, exposure duration of 0.1 seconds, and power sufficient to produce barely visible burns in a grid pattern. We treated the thickened retina and non-thickened area of the macula excluding central 500 micron. Microaneurysms within the macular areas were treated by focal application of laser shots sufficient to bleach them. RESULTS: The study comprised 86 eyes of 52 patients who were treated by applying 180 to 360 burns with a mean of 275+/-51. Mean macular thickness differed significantly between time points (Wilks' Lambda 0.139; F (2, 6) = 125.95; p = 0.00001). Mean visual acuity changed significantly between time points (Wilks' Lambda 0.535; F (4, 82) = 17.8; p = 0.00001). At the last follow-up, visual acuity improved at least one line in 32(37.2%) eyes, remained stable in 48(55.8%) eyes, and declined in 6(6.9%) eyes. CONCLUSIONS: Modified mild macular grid is an effective and safe procedure for patients with diffuse diabetic macular oedema. PMID- 27183930 TI - Burnout and quality of life in nurses of a tertiary care hospital in Pakistan. AB - OBJECTIVE: To determine the relationship of burnout and quality of life among nurses of different departments at a tertiary care hospital. METHODS: The observational, cross-sectional study was conducted at Mayo Hospital, Lahore, from November 2013 to May2014, and comprised nurses recruited by convenience sampling. Maslach Burnout Inventory was used to assess burnout and World Health Organisation Quality of life instrument's BREF version was used to assess quality of life of the subjects. Data was analysed using SPSS 16. RESULTS: Of the 106 nurses with a mean age of 35.5+/-7 years, 83(79%) were experiencing severe burnout and a low quality of life. Nurses of Surgery and Obstetrics/Gynaecology departments who worked longer hours on the night shift scored higher on burnout and lower on quality of life. CONCLUSIONS: Burnout in nurses was very common because of increasing workload and can negatively affect their quality of life leading to compromised patient care. PMID- 27183932 TI - Learning environment, approaches to learning and learning preferences: medical students versus general education students. AB - OBJECTIVE: The main objective of the study was to see whether medical students use more desirable approaches to studying than general education students. METHODS: Survey method was used to collect data from both the medical students and the general education students. The survey of the medical students was carried out between January and March, 2012. The survey was administered to all the medical students present in lecture halls on day of data collection, while general education students were randomly selected from four subject areas at two universities. RESULTS: In total, 976 medical students and 912 general students participated in the study. Of the general students, 494(54%) were boys and 418(46%)were girls with an overall mean age of 20.53+/-1.77 years (range: 17-27 years). The medical students' perceptions of their learning environment and their learning preferences were broadly similar to that of general education students with the exception of workload. The medical students perceived the workload to be less appropriate (Mean = 2.06+/-0.72) than the students in general education (Mean = 2.84+/-0.90). The medical students were more likely to use the deep approach to studying (Mean = 3.66+/-0.59) than the students in general education (Mean = 3.16+/-0.91). The students in general education were slightly more likely to use the organized studying (Mean = 3.44+/-0.90) than the medical students (Mean =3.23+/-0.90). Both medical students and the students in general education tended to use the surface approaches along with other approaches to studying. CONCLUSIONS: There was not a great difference between the medical students and the students pursuing general education with regard to perceptions of the learning environment and approaches to learning. PMID- 27183933 TI - Analysis of association between type of amblyopia and gender at a tertiary care hospital in Karachi. AB - OBJECTIVE: To analyse the frequency of different types of amblyopia and its association with gender. METHODS: The cross-sectional study was conducted from March 2014 to October 2014 at the Department of Ophthalmology of a tertiary care hospital inKarachi. The patients were classified into different types of amblyopia like anisometropic, strabismic, sensory deprivation and meridional amblyopia. Stratification was done according to age, gender and type of amblyopia by using SPSS version 21. RESULTS: Out of 130 patients, 71 were male and 59 were female. The amblyopia rate determined was anisometropic 69.23%, strabismic amblyopia 21.51% and others 9.23%. The mean age of subjects was 18.02+/-9 years. Type of amblyopia was independent of gender, and anisometropic amblyopia was the most common type of amblyopia found in both genders. CONCLUSIONS: This study found no significant association between gender and types of amblyopia and anisometropic amblyopia was the most common type of amblyopia in the data collected. PMID- 27183934 TI - Fibroblast growth factor 2 improves cognitive function in neonatal rats with hypoxic ischaemic brain injury. AB - OBJECTIVE: To determine the effect of fibroblast growth factor 2 on cognitive function in neonatal rats with hypoxic-ischaemic brain injury. METHODS: The randomised controlled study was conducted from January to June 2011 at Mersin University, School of Medicine, Experimental Animals Research Laboratory and Physiology Behaviour Laboratory, Mersin, Turkey. It included 7-d-old male rats that were randomised into four groups: fibroblast growth factor 2-20, fibroblast growth factor 2-40, control and sham. All the rats, except those in the sham group, were kept in a hypoxia chamber containing 8% oxygen for 2 hours following ligation of the right carotid artery. After hypoxic-ischaemic brain injury was induced, 20 ng g-1 or 40 ng g-1 of fibroblast growth factor 2 was administered via the intraperitoneal route. The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling method was used to evaluate neuronal apoptosis. The Morris water maze (MWM) test was administered to the rats at age 14 weeks. RESULTS: Of the 78 rats on the study, 18 (23%) were in the sham group, while the other three groups had 20 (25.6%) rats each. The number of apoptotic neurons in the right hemisphere in the experimental groups was significantly lower than in the control group (p=0.004 and p<0.001). The number of apoptotic neurons in the right hemisphere in the fibroblast growth factor 2-40 group was significantly lower than in the fibroblast growth factor 2-20 group (p<0.001). Moreover, fibroblast growth factor 2improved Morris water maze test cognitive performance in a dose-dependent manner. CONCLUSIONS: Fibroblast growth factor 2 treatment reduced neuronal apoptosis and improved cognitive functioning in neonatal rats with experimentally-induced hypoxic-ischaemic brain injury. PMID- 27183935 TI - Characteristics of the patients undergoing surgical treatment for pneumothorax: A descriptive study. AB - OBJECTIVE: To identify the characteristic features of pneumothorax patients treated surgically. METHODS: The retrospective study was conducted at Gazi Yasargil Education and Research Hospital Thoracic Surgery Clinic, Diyarbakir, Turkey and comprised records of pneumothorax patients from January 2004 to December 2014. They were divided into two groups as spontaneous and traumatic. Patients who had not undergone any surgical intervention were excluded. Mean age, gender distribution, location of the disease, type of pneumothorax, and treatment method were noted. Among patients with spontaneous pneumothorax, age and months distribution, smoking habits, pneumothorax size, and treatment method were assessed. The effect of gender, location, comorbid disease, smoking, subgroup of disease, and pneumothorax size on surgical procedures were also investigated. RESULTS: The mean age of the 672 patients in the study was 34.5+/-6.17 years. There were 611(91%) men and 61(9%) women. Disease was on the right side in 360(53.6%) patients, on the left side in 308(45.8%), and bilateral in 4(0.59%). Besides, 523(77.8%) patients had spontaneous, and 149(22.7%) had traumatic pneumothorax. Overall, 561(83.5%) patients had been treated with tube thoracostomy, whereas 111(16.5%) were treated with thoracotomy/thoracoscopic surgery. The presence of comorbid diseases, being primary, and being total or subtotal according to partial were found to create predisposition to thoracotomy/ thoracoscopic surgery (p<0.05 each). CONCLUSIONS: In the case of pneumothorax being total, the presence of comorbid diseases, and the increase in pneumothorax size, thoracotomy or thoracoscopic surgery is preferred. PMID- 27183936 TI - Comparison of primary versus recurrent pterygium after intralesional 5 Fluorouracil. AB - OBJECTIVE: To compare the mean change in corneal astigmatism and clinical appearance after intralesional injection of 5-Fluorouracil in primary and recurrent pterygia. METHODS: The quasi-experimental study was conducted at the Armed Forces Institute of Ophthalmology, Rawalpindi, Pakistan, from June 2014 to April 2015. The patients were categorised into two groups. Group1 named GP comprised primary pterygia patients, while those of recurrent pterygia were in Group 2 named GR. All the patients were treated with 0.1ml intralesional 5 Fluorouracil 5mg weekly injections for 04 weeks. Ophthalmic clinical evaluation included uncorrected distant visual acuity, keratometery and slit lamp examination was performed before and 04 weeks after the treatment. RESULTS: There were 86 eyes of 64 patients in the study. Mean uncorrected distant visual acuity of patients was 0.12+/-0.13 in GP and 0.26+/-0.17 in GR. Mean astigmatism before treatment was 1.75+/-1.08 in GP and 2.92+/-2.28 in GR. Same parameters 04 weeks after last injection were 1.66+/-1.17 and 2.64+/-1.78 in GP and GR respectively. All eyes had a statistically significant change in clinical appearance. CONCLUSIONS: Intralesional 5-Fluorouracil injection improved cosmesis of primary as well as recurrent pterygia, but did not have statistically significant effect on corneal astigmatism. PMID- 27183937 TI - Burden of rheumatological disorders in a tertiary care hospital. AB - OBJECTIVE: T To evaluate the frequency of different rheumatological disorders in patients visiting a tertiary care centre. METHODS: The retrospective analysis was conducted at the Rheumatology Clinic of Jinnah Postgraduate Medical Centre, Karachi, and comprised prospectively collected data of patients with different musculoskeletal disorders from February 2004 to February 2014. Detailed history, examination and laboratory investigations were recorded in a pre-designed structured proforma. The frequency, demographic characteristics and associated co morbidities were studied. SPSS 17 was used for statistical analysis. RESULTS: Of the 603 patients whose data was analysed, 460(76.3%) were women and 143(23.7%) were men. Overall mean age of the patients was 35.2+/-12 years. Rheumatoid arthritis was diagnosed in 458(76%) patients, systemic lupus erythematosus in 42(7%) ankylosing spondylitis in 32(5.3%), mixed connective tissue disease in 22(3.6%) and scleroderma in 12(2%) patients. CONCLUSIONS: Rheumatological disorders constitute a major disease burden in a relatively young population of patients. RA was the most common disorder seen in our clinic, as seen elsewhere also, followed by SLE, AS, MCTD, etc. PMID- 27183938 TI - Clinical and polysomnographic features of patients with Restless Legs Syndrome. AB - OBJECTIVE: To reveal clinical and polysomnographic features in patients treated for restless leg syndrome, and to examine the compatibility of sleep data and clinical features. METHODS: The study was conducted at the Department of Neurology, Ankara Numune Training and Education Hospital, Ankara, Turkey, and comprised patients who presented to the outpatient clinic between January and July 2014 who were diagnosed with restless leg syndrome based on the International RestIess Leg Syndrome Study Group criteria. Patients underwent polysomnography test in spontaneous sleep in a single room. SPSS 18 was used for statistical analyses. RESULTS: Of the 18 patients, 13(72%)were females and 5(28%)were males. Overall mean age was 51.56+/-11.57years (range: 23-66 years). Fourteen (77.8%) patients reported insomnia; 10(55.5%) patients had excessive daytime sleepiness; 13(72.2%) reported snoring; and 3(17%) had apnoea. Mean International Restless Legs Syndrome Study Group Rating Scale score was 26.11+/ 7.9 (range: 16-40).Mean Epworth Sleepiness Scale score was 9.17+/-5.1 (range: 0 20). CONCLUSIONS: Restless leg syndrome was more common in women and the most common complaint was insomnia. PMID- 27183939 TI - Assessment of mental workload and academic motivation in medical students. AB - OBJECTIVE: To investigate the level of correlation and direction of linearity between academic motivation and subjective workload. METHODS: The study was conducted at Baskent University School of Medicine, Ankara, Turkey, from December 2013 to February 2014, and comprised Phase 5 Phase 6 medical students. Subjective workload level was determined by using National Aeronautics and Space Administration Task Load Index scale that was adapted to Turkish. Academic motivation values were obtained with the help of Academic Motivation Scale university form. SPSS 17 was used for statistical analysis. RESULTS: Of the total 105 subjects, 65(62%) students were in Phase 5 and 40(38%) were in Phase 6. Of the Phase 5 students, 18(27.7%) were boys and 47(72.3%) were girls, while of the Phase 6 students, 16(40%) were boys and 24(60%) were girls. There were significant differences in Phase 5 and Phase 6 students for mental effort (p=0.00) and physical effort (p=0.00). The highest correlation in Phase 5 was between mental effort and intrinsic motivation (r=0.343). For Phase 6, highest correlation was between effort and amotivation (r= -0.375). CONCLUSIONS: Subjective workload affected academic motivation in medical students. PMID- 27183940 TI - Quality of life of Pakistani medical students studying in a private institution. AB - OBJECTIVE: To find the quality of life of medical students using a World Health Organisation questionnaire. METHODS: The cross-sectional study was conducted in February 2015 at Shifa College of Medicine, Islamabad, Pakistan, and comprised students studying in an integrated medical education system. The shortened version of World Health Organisation Quality of Life questionnaire comprising 26 items was used. Consecutive non-probability sampling was used to collect data which was analysed using SPSS 21. RESULTS: Out of 417 medical students, 185(44.4%) were male and 232(55.6%) were female. Of them, 165(39.6%) were in pre clinical years, while 252(60.4%) were in clinical years. Overall, 347(83.2%) students rated their quality of life as "good" or "very good". Environmental domain had the highest mean score of 70.43+/-16.38 while Psychological Health domain had the lowest mean score of 66.48+/-15.64. CONCLUSIONS: Medical education affects students' health, thus their quality of life varies. Identification of this is very important, since long-term stress can induce some permanent personality changes in individuals. PMID- 27183941 TI - Clinical features and outcomes of Candidaemia in cancer patients: Results from Pakistan. AB - OBJECTIVE: To evaluate clinical risk factors and outcomes among cancer patients with candidaemia at a large cancer treatment centre. METHODS: The retrospective study was conducted at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, and comprised data related to all cancer patients with a positive blood culture for candida species between January 1995 and December 2013. RESULTS: A total of 311 patients were identified and there were 16 positive candida cultures among every 1000 (1.6%) cultures positive for any microorganism. Patients with haematological malignancies (adjusted odds ratio:2.23), those in shock (adjusted odds ratio: 9.48) were significantly more likely to die during the index hospitalisation, while patients with candida albicans isolated from the blood culture (adjusted odds ratio: 0.47) and those who received antifungal agent based on the sensitivity report of the fungal culture (adjusted odds ratio:0.32) were significantly less likely to die. Receipt of antifungal agents on an empirical basis before a positive culture was not significantly associated with mortality (p>0.05). CONCLUSIONS: No statistically significant risk factor for candidemia was identified, but haematological malignancies, shock and candidaemia due to non-albicans species were predictors of mortality during index hospitalisation. PMID- 27183942 TI - Outcome of VVF repair without omental interposition. AB - OBJECTIVE: To find out the outcome in cases of vesicovaginal fistula repair. METHODS: The descriptive study was conducted at the District Headquarter Hospital, Timergara, Lower Dir, Pakistan, from November 1, 2011 to November 2013, and comprised all patients admitted in Urology unit with vesicovaginal fistula. Repair was done with either transabdominal or transvaginal approach. Repair technique involved good tissue separation, interrupted sutures, and no omental interposition. Follow-up was of three months. RESULTS: There were 30 patients available, but 2(6.6%) were excluded. Among the remaining 28(93.3%) patients dehiscence was not noted in any patient, while only 4(14.3%) patients developed mild urinary tract infection. There were no intraoperative or postoperative deaths. CONCLUSIONS: Transvaginal or Transabdominal repair of vesicovaginal fistula is successful treatment modality if good dissection and tissue separation is applied with interrupted suturing. Omental interposition is not essential for good healing. PMID- 27183943 TI - Medical errors and patient safety in the operating room. AB - OBJECTIVE: To investigate medical errors in the operating room, attitudes of healthcare professionals in case of errors and educational needs of professionals. METHODS: The descriptive study was conducted at a university hospital in Turkey from January 25 to February 14, 2011, and comprised operating room staff, including physicians, nurses, anaesthesia technicians and perfusion technicians. Data was obtained using a questionnaire. RESULTS: Of the 69 respondents, 45(65.2%) had experienced medical errors and 29(42%) had verbally warned the person who caused the error. The main cause of the medical errors was a lack of healthcare professionals and their inadequate qualifications, 51(73.9%); and insufficient communication, 41(59.4%). Coping with stress and communication 45(65.2%) and radiation safety 28(40.6%) were the most common educational needs. CONCLUSIONS: Patient safety applications in the operating room can be improved by offering educational programmes, designing an easy reporting system, encouraging reporting of medical errors and active participation of healthcare professionals in decisions that might affect patient safety. PMID- 27183944 TI - Effect of body mass index on outcome of labour induction. AB - The retrospective study to explore the adverse effect of obesity on pregnancy and labour was conducted at Aga Khan University Hospital, Karachi, Pakistan, and comprised data of all patients booked between 12-14 weeks and required induction of labour from January 1 to December 31, 2012. Women were grouped into two body mass index categories: normal weight (<22.9 kg/ m2) as controls and exposed group (>23 kg/m2). Obesity increased the risk of development of gestational hypertension and diabetes. Therefore obese women were more likely to be induced due to medical indication whether primiparous or multiparous adjusted odds ratio =2.89(95% confidence interval 1.29-6.48) and 2.77 (95% confidence interval 1.07 7.19) respectively. There was increased chance of having caesarean section in primigravida adjusted odds ratio = 1.45 (95% confidence interval 0.72-2.92), duration of caesarean section and blood loss during the procedure were not significantly associated with high body mass index (p>0.05). Obesity may lead to a lot of problems in primigravida, but it did not have major impact. PMID- 27183945 TI - Epidemiology of drowning and near drowning at Karachi beaches from 2012 to 2014. AB - Karachi Municipal Corporation's Emergency Response Center's lifeguards save drowning individuals, recover dead bodies of drowned individuals, and provide first aid care to injured victims of near-drowning and road traffic accidents on the road along the various beaches.Cumulatively302 drowning and near-drowning 302 incidents were recorded from 2012 to 2014, with 291 (96.3%) incidents involving males. One hundred ninety-six (64.9%) individuals were saved from drowning, out of which 116 (59.2%) were saved on Sundays, followed by 31 (15.8%) on Saturdays; with 79 (40.3%) being saved during the hours 06:00 PM to 07:59 PM. Out of total 34 dead bodies were recovered, Sundays registered 8 (23.5%) such incidents. Out of the 72 individuals who received first-aid care, 60 (83.3%) received it on Sundays and Saturdays. The months of April, May, and June were the peak months of incidents for saving from drowning. Results augur the need for targeted health education campaigns, especially during summer months. PMID- 27183946 TI - An establishment of vascular access through superior vena cava for a patient with multiple central venous stenosis or occlusion. AB - The patency of vascular access is of vital importance to dialysis patients. Access dysfunction is largely caused by vessel stenosis and thrombosis. Nephrologists usually find themselves helpless when all treatments fail and the vascular access seems to have exhausted. Here we report a successful establishment of vascular access through superior vena cava for a critical patient with multiple central venous stenosis or occlusion. To our knowledge, it is the first case ever reported on the successful establishment of vascular access through superior vena cava under such a complicated condition of vascular exhaustion. PMID- 27183947 TI - Non-functional paraganglioma of the mediastinum. AB - Paragangliomas are rare tumours which have the ability to secrete neuropeptide and catecholamines. Frequently, the clinical presentation of these tumours is ill defined and some may have no symptoms whatsoever until the tumour is large enough to cause symptoms secondary to local invasion and mass effect, hence making paragangliomas a challenge to diagnose and manage surgically. We report a case of a 55 year old female who presented with shortness of breath and chest pain for 3 years. Further investigations led to the demonstration of a mass along the left side of the mediastinum which was suggestive of a neoplasm. Complete surgical resection of the tumour was achieved and the patient was discharged uneventfully. PMID- 27183948 TI - Neonatal Bartter Syndrome in association with congenital adrenal hyperplasia in a neonate - a rare combination. AB - Neonatal Bartter syndrome (NBS) is an autosomal recessive renal tubulopathy characterized by hypokalaemic, hypochloraemic metabolic alkalosis associated with increased urinary loss of sodium, potassium, calcium and chloride. There is hyperreninaemia and hyperaldosteronaemia but normotension. Congenital adrenal hyperplasia (CAH), another autosomal recessive condition, may present in the neonatal period with vomiting, hypovolaemia, failure to gain weight or ambiguous genitalia. We report a case of NBS and CAH combination in a neonate. A male neonate born at term was admitted with history of recurrent vomiting and dehydration episodes. Investigations revealed electrolytes imbalance, metabolic alkalosis, raised aldosterone and renin levels suggestive of NBS. He was treated successfully and discharged. He was re-admitted with the same symptoms. Further evaluation confirmed the presence of CAH as well. We report this case because of the rarity of this combination (NBS plus CAH) and to the best of our knowledge this is the first such case report from Pakistan. PMID- 27183950 TI - Unmasking of myasthenia gravis during pegylated Alfa 2 a interferon and ribavirin therapy for chronic hepatitis C. AB - Over last few decades, hepatitis C has emerged as a serious infection that has threatened the health and budgets of millions in the world. The objective of health professionals to treat it with recommended therapy of Alfa interferon and Ribavirin combination presents certain risks. One of the alarms is the ability of interferon to stimulate the production of autoantibodies in the body resulting in expression of autoimmune diseases in few who develop these antibodies. The case presented here is about unmasking of myasthenia gravis in a patient who received alfa interferon therapy for her chronic hepatitis C. Alfa interferon probably plays an important role in manifestation of the diseases in susceptible patients and all autoimmune diseases cannot be taken as mere side effects of the therapy. Clinicians need to be alert to pick up these diseases earlier so that the prompt management is possible. PMID- 27183949 TI - Auxiliary partial orthotopic liver transplant for Criggler-Najjar Syndrome: Report of 2 cases from Pakistan. AB - Auxiliary partial orthotopic liver transplant (APOLT) is a treatment option for certain liver disorders where liver structure is preserved. It includes Criggler Najjar syndrome (CNS), urea cycle defects and familial hypercholesterolaemia. Liver transplant as a treatment modality has only recently become available in Pakistan. Here we report two paediatric cases of CNS type 1 where auxiliary liver transplant was performed to correct jaundice and prevent inevitable brain damage. Both recipients and their respective living donors had successful surgery and are doing well. PMID- 27183951 TI - The overlooked side of convulsion: bilateral posterior fracture and dislocation of proximal humerus. AB - Injuries after an epileptic convulsion have been seen commonly such as burns, head injury and dislocation of the extremities. But fractures of the extremities due to convulsion are rare. External trauma mechanism is not necessary for extremity fractures. Muscle contractions can cause increased load on the skeleton and it can be complicated by dislocation andor fracture of extremities. Almost 1 4% of all the shoulder dislocations are posterior. In this case report we present a 32 year old male patient who had bilateral posterior fracture and dislocation of proximal humerus after convulsion. We would like to emphasize that it is so important to make systemic examination and evaluation of the patients who were admitted to emergency department after epileptic convulsion. PMID- 27183952 TI - Female sexual dysfunction: Assessment. AB - Female sexual dysfunction (FSD) is a common complex clinical condition, with multiple etiologies, association and pathophysiologic correlations. This review includes the definition, etiology, and diagnosis of FSD. It calls for a bio psychosocial approach to FSD management, which incorporates, but is not limited to, only the psychological aspects of FSD. PMID- 27183953 TI - Weekend therapy in diabetes. AB - This article introduces the concept of "weekend therapy", which has now become reality in diabetes. It briefly describes injectable and oral drugs which are currently available, or are in advanced stages of development, for use in once weekly administration. These include dulaglutide, exenatide QW, semaglutide, omarigliptin and trelagliptin. PMID- 27183955 TI - Highly-oriented molecular arrangements and enhanced magnetic interactions in thin films of CoTTDPz using PTCDA templates. AB - In the present work, the templating effect of thin layers of perylene-3,4,9,10 tetracarboxylic dianhydride (PTCDA) on the growth of cobalt tetrakis(thiadiazole)porphyrazine (CoTTDPz) thin films was examined. X-ray diffraction and optical absorption spectra indicate that while CoTTDPz forms amorphous thin films on the bare substrates, it forms crystalline thin films on the PTCDA templates, in which the molecular planes of CoTTDPz are considered to be parallel to the substrates. Magnetic measurements reveal a significantly enhanced antiferromagnetic interaction of CoTTDPz in the templated thin films, with values reaching over 13 K. The ability to generate crystalline films and to control their orientation using molecular templates is an important strategy in the fields of organic electronics and spintronics in order to tailor the physical properties of organic thin films to suit their intended application. PMID- 27183954 TI - Factors contributing to early menarche in school girls. AB - OBJECTIVE: To assess the average age of menarche in Pakistani girls from different socioeconomic backgrounds. METHODOLOGY: This was a cross sectional study design carried out on female students studying in different schools of Karachi in 2014. Girls aged 10-14 years age were included. Schools from all three socio economic strata were selected through random sampling technique from a list of schools having health care services. Data was collected through a self administered questionnaire translated in Urdu where required. Height and Weight was measured through calibrated instruments. Sample size was n=385 based on maximum proportion of 50%. Analysis was done on SPSS version 20. Chi-square and ANOVA was applied after checking data for normality. RESULTS: The total sample size was 275 after excluding poorly filled questionnaires. The mean age of menarche in our sample population was 11.73+/-1.2 years. Out of the total participants 127 (46%) students had reached the age of menarche. It was found that mean age of menarche was highest in participants of Kashmiri origin 14.5+/ 0.1 years and lowest mean age was observed in those of Gujrati origin at 11.0+/ 0.1 years (p 0.036). When mean age of menarche was compared with socioeconomic class highest mean age was observed in lower class 12.13 +/-0.1 (p 0.268). CONCLUSIONS: Our study reveals a decline in the mean age of menarche of at least 2 years in girls aged 10-14 years. PMID- 27183956 TI - United States neurosurgery annual case type and complication trends between 2006 and 2013: An American College of Surgeons National Surgical Quality Improvement Program analysis. AB - We aimed to identify trends in the neurosurgical practice environment in the United States from 2006 to 2013 using the American College of Surgeons-National Surgical Quality Improvement Program (NSQIP) database, and to determine the complication rate for spinal and cranial procedures and identify risk factors for post-operative complications across this time period. We performed a search of the American College of Surgeons-NSQIP database for all patients undergoing an operation with a surgeon whose primary specialty was neurological surgery from 2006 to 2013. Analysis of patient demographics and pre-operative co-morbidities was performed, and multivariate analysis was used to determine predictors of surgical complications. From 2006 to 2013, the percentage of spinal operations performed by neurosurgeons relative to cranial and peripheral nerve cases increased from 68.0% to 76.8% (p<0.001) according to the NSQIP database. The proportion of cranial cases during the same time period decreased from 29.7% to 21.6% (p<0.001). The overall 30-day complication rate among all 94,621 NSQIP reported patients undergoing operations with a neurosurgeon over this time period was 8.2% (5.6% for spinal operations, 16.1% for cranial operations). The overall rate decreased from 11.0% in 2006 to 7.5% in 2013 (p<0.001). Several predictors of post-operative complication were identified on multivariate analysis. PMID- 27183957 TI - Resolution of third nerve palsy despite persistent aneurysmal mass effect after flow diversion embolization of posterior communicating artery aneurysms. AB - Posterior communicating artery (PCOM) aneurysms may cause third nerve palsies. The optimal treatment with clipping versus coiling remains controversial. Here we report on two cases of resolution of third nerve palsy after flow diversion embolization of large and giant PCOM aneurysms without adjuvant coil placement. The resolution of third nerve palsy was not preceded by significant shrinkage of the aneurysmal sac on MRI. However, one patient showed resolution of T2-weighted signal abnormalities in the midbrain and mesial temporal lobe despite a similar size of the aneurysm. Therefore, flow diversion embolization of a PCOM aneurysm may resolve oculomotor nerve palsies through decreasing arterial pulsations against the nerve or midbrain. PMID- 27183958 TI - Neurological complications of acute multifocal placoid pigment epitheliopathy. AB - Acute multifocal placoid pigment epitheliopathy (AMPPE) is an autoimmune chorioretinal disease that can be complicated by neurological involvement. There is limited information on this potentially treatable condition in the neurological literature. The objective of this patient series is to describe the neurological complications of AMPPE. We retrospectively identified patients with neurological complications of AMPPE seen at Auckland Hospital between 2008 and 2013 and summarised cases in the literature between 1976 and 2013. We identified five patients with neurological complications of AMPPE at Auckland Hospital and 47 reported patients. These patients demonstrated a spectrum of neurological involvement including isolated headache, stroke or transient ischaemic attack, seizures, venous sinus thrombosis, optic neuritis, sensorineural hearing loss and peripheral vestibular disorder. We propose criteria to define AMPPE with neurological complications. A cerebrospinal fluid (CSF) lymphocytosis in a patient with isolated headache may predict the development of cerebrovascular complications of AMPPE. Patients with cerebrovascular complications of AMPPE have a poor prognosis with high rates of death and neurological disability among survivors. Predictors of poor outcome in those who develop neurological complications of AMPPE are a relapsing course, generalised seizures and multifocal infarction on MRI. All patients with neurological complications of AMPPE, including headache alone, should be investigated with an MRI brain and CSF examination. Patients with focal neurological symptoms should receive intravenous (IV) methylprednisolone followed by a tapering course of oral steroids for at least 3months. Patients with AMPPE and an isolated headache with a CSF pleocytosis should be treated with oral steroids. PMID- 27183960 TI - Margaret McCartney: We need more openness on GPs' pay. PMID- 27183959 TI - Species-specific mutual regulation of p53 and miR-138 between human, rat and mouse. AB - In recent years, p53 was identified to regulate the expression of many miRNAs and was also regulated by miRNAs. In this paper, we found that miR-138 showed a pronounced increase after p53 activation in human non-small cell lung cancer (NSCLC) cells, which is mediated by p53 binding sites in the promoter region of its host gene, but this did not happen with rat and mouse cells. More interestingly, we found that p53 could be also regulated by miR-138 in mouse and rat cells, but not in the human NSCLC cells. Our results suggest the existence of species-specific differences of the regulations of miRNA against its targets and the regulations of miRNA itself by other proteins. PMID- 27183961 TI - Increased nuchal translucency thickness and risk of neurodevelopmental disorders. AB - OBJECTIVE: To investigate the association between fetal nuchal translucency (NT) thickness and neurodevelopmental disorders in euploid children. METHODS: This study included 222 505 euploid children who had undergone routine first-trimester screening during fetal life. Children were divided according to prenatal NT into three groups: NT < 95th percentile (n = 217 103 (97.6%)); NT 95th -99th percentile (n = 4760 (2.1%)); and NT > 99th percentile (n = 642 (0.3%)). All children were followed-up to a mean age of 4.4 years. Information on diagnoses of intellectual disability, autism spectrum disorders (ASD), cerebral palsy, epilepsy and febrile seizures was obtained from national patient registries. RESULTS: There was no excess risk of neurodevelopmental disorders among euploid children with first-trimester NT 95th -99th percentile. For children with NT > 99th percentile, there were increased risks of intellectual disability (odds ratio (OR), 6.16 (95% CI, 1.51-25.0), 0.31%) and ASD (OR, 2.48 (95% CI, 1.02 5.99), 0.78%) compared with children with NT < 95th percentile (incidence of 0.05% for intellectual disability and 0.32% for ASD), however, there was no detected increase in the risk of cerebral palsy (OR, 1.91 (95% CI, 0.61-5.95), 0.47%), epilepsy (OR, 1.51 (95% CI, 0.63-3.66), 0.78%) or febrile seizures (OR, 0.72 (95% CI, 0.44-1.16), 2.65%). CONCLUSIONS: In a large unselected cohort of euploid children, there was no increased risk of neurodevelopmental disorders among those with a first-trimester NT 95th -99th percentile. Among euploid children with first-trimester NT > 99th percentile, there were increased risks of intellectual disability and ASD, but the absolute risk was reassuringly low (< 1%). Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 27183962 TI - Play in juvenile mink: litter effects, stability over time, and motivational heterogeneity. AB - Mink are potentially ideal for investigating the functions of play: deleterious effects of early social isolation suggest a crucial developmental role for play; and huge numbers of highly playful juvenile subjects can be studied on farms. We collected descriptive data on 186 pairs from 93 litters, half provided with play eliciting environmental enrichment objects in their home cages, to test three hypotheses: (1) play frequency is subject to litter effects; (2) relative playfulness is stable over time; (3) play sub-types share a single, common motivational basis. We found weak litter effects that were driven by stronger litter effects on general activity, and weakly stable individual differences in both total and rough-and-tumble play. Experimentally increasing object play did not inhibit rough-and-tumble play, showing these sub-types are not motivational substitutes. Frequencies of these sub-types were also uncorrelated, and changed differently with time of day and age, further supporting this conclusion. PMID- 27183963 TI - Self-Employment among Same-Sex and Opposite-Sex Couples in Canada. AB - This study presents novel evidence on the relationship between sexual orientation and self-employment. Using data from the 2001 and 2006 Census of Canada and the 2011 Canadian National Household Survey, we explore the propensity for self employment among same- and opposite-sex couples. We examine the demographic, human capital, and family characteristics of coupled gay men and lesbians relative to their coupled heterosexual counterparts to offer potential mechanisms generating differences in rates of self-employment. Our analysis further considers occupational variability in the likelihood of self-employment. We find that gay men are less likely and lesbians more likely than heterosexuals to be self-employed; however, there is significant variation across occupations. Gay men are more likely to be self-employed in arts and culture, sales and service, and natural and applied sciences, but less likely in business, finance, and health-related occupations. Lesbians are much more likely to be self-employed in health-related occupations, natural and applied sciences, and arts and culture. Marriage and having children are significant predictors of self-employment for coupled heterosexual women but not lesbians. Cette etude presente des evidences empiriques concernant la relation entre l'orientation sexuelle et le travail independant. Utilisant des donnees provenant du Recensement du Canada de 2001 et de 2006, ainsi que l'Enquete nationale aupres des menages (ENM) de 2011, nous explorons la tendance du travail independant parmi les couples de meme sexe et ceux de sexe oppose. Ainsi, nous examinons les caracteristiques demographiques, du capital humain et familiales des couples gais et lesbiens par rapport a leurs homologues heterosexuels, afin de demontrer une correlation entre l'orientation sexuelle et la probabilite d'etre travailleur independant - une causation qui nous semble evident et que nous analysons plus en profondeur. Nous concluons d'ailleurs que les hommes gais sont moins probables - et les lesbiennes plus probables - d'etre travailleurs independants que les heterosexuels. Cependant, il existe des variantes significatives entre les differentes occupations. Les hommes homosexuels tendent plutot a etre travailleurs independants dans les domaines des arts et de la culture, la vente et les services, ainsi que les sciences pures et les sciences naturelles. Par contre, ils le sont moins dans les domaines des affaires, de la finance et des domaines relies a la sante. De leur cote, les femmes homosexuelles tendent plutot a etre travailleuses independantes dans les domaines relies a la sante, aux sciences pures et aux sciences naturelles, ainsi qu'aux arts et la culture. Finalement, le fait d'etre marie et d'avoir des enfants sont des indicateurs significatifs du travail independant pour les femmes en couples heterosexuels, mais pas pour les lesbiennes. PMID- 27183964 TI - From Porter to Bourdieu: The Evolving Specialty Structure of English Canadian Sociology, 1966 to 2014. AB - How has English Canadian sociology changed from 1966 to 2014? Has it become more intellectually fragmented or cohesive over time? We answer these questions by analyzing cocitation networks extracted from 7,141 sociology articles published in 169 journals. We show how the most central early specialties developed largely in response to John Porter's The Vertical Mosaic. In later decades, the discipline diversified, fragmented, and then reorganized around a new set of specialties knit together by the work of Pierre Bourdieu. The discipline was most intellectually fragmented in periods where multiple specialties were emerging or declining concurrently (i.e., 1975 to 1984 and 1995 to 2004), and was more structurally cohesive from 2005 to 2014 than in any previous period. Comment est ce que la sociologie canadienne-anglaise a-t-elle change entre 1966 et 2014? Est elle devenue plus intellectuellement fragmentee ou coherente avec le temps? Nous repondons a ces questions en analysant des reseaux de co-citation qui ont ete deduits de 7,141 articles publies par 169 journaux. Nous demontrons les specialites primordiales se sont developpees en reponse de The Vertical Mosaic de John Porter. Durant les decennies suivantes, la discipline s'est diversifiee, fragmentee et puis s'est reorganisee autour d'une nouvelle serie de specialites liees ensemble par le travail de Pierre Bourdieu. La discipline etait la plus intellectuellement fragmentee durant les periodes ou plusieurs specialites emergeaient ou declinaient concurremment (par exemple de 1975 a 1985 et de 1995 a 2004). Par contre, elle etait plus coherente que tous les autres periodes entre 2005 et 2014. PMID- 27183965 TI - The Missing Memory of Canadian Sociology: Reflexive Government and "the Social Science". AB - The modest literature on the history of Canadian Sociology takes the appearance of a named academic discipline as its object. Canadian Sociology is held to have had some precursors in the 1880s, but really to appear only in the 1920s. It is described as a foreign import and as an activity first of intellectual speculation and moral reform. Observational and analytic practice are absent before 1880. The activities of state agents and government departments in the social field are not discussed. This article offers a richer account through an examination of the larger field from which Sociology was extracted, "the social science," which was practiced actively in colonial Canada from the early nineteenth century. The social science shaped and was itself shaped by colonial conditions. The article outlines three interrelated moments in social science to carry its claims: inventory-making, the emergence of "population-thinking," and "reflexive government." Attending to the social science underlines the complex and convoluted relations of sociology with state power. Les rares oeuvrages academiques portant sur l'histoire de la sociologie canadienne prend pour objet l'apparition du terme dans le contexte universitaire. Dans cet optique, ils signalent certains precurseurs de la sociologie canadienne des les annees 1880, mais en fait ils affirment que cette discipline n'apparait que dans les annees 1920. Cette discipline est presentee comme une importation academique et, d'abord et avant tout, comme de la speculation intellectuelle et comme un projet de reforme morale. D'apres cette vision, les pratiques d'observation et d'analyse sociales ne semblent pas exister avant 1880, et les acteurs politiques et administratifs sont absents du terrain. Notre article propose un examen plus riche du vaste champ duquel la sociologie academique fut arrachee: activement pratiquee au Canada a l'epoque coloniale des le debut du XIXe siecle. La science sociale forma et fut formee par les conditions sociales et politiques existant dans la colonie. Notre article expose trois moments pertinents et inter-relies de la science sociale: la fabrication d'inventaires sociaux; l'emergence du , et l'exercice du . La reintegration de l'histoire de la sociologie canadienne dans la science sociale accentue la relation complexe et incontournable entre sociologie et pouvoir etatique. PMID- 27183966 TI - Legitimizing Security in the Ivory Tower: Canadian University Corporate Security Services' Public Quest for Legitimacy. AB - This article examines how university corporate security (UCS) services engage in legitimation work in their attempts to make their university communities (i.e., faculty, staff, students) and political masters (i.e., university administrators, boards of governors, senators) believe that they are honest, trustworthy, and caring and have authority that should be deferred to. This is accomplished through the analysis of interview and observational data collected as part of a research project exploring UCS services at five Canadian universities and an examination of how UCS services at 14 Canadian universities communicate using the social media service Twitter. These UCS services were found to primarily use Twitter for the purposes of soliciting or requesting information and for networking. In communicating through Twitter, UCS services engage in public legitimation work in which they make claims about and attempt to demonstrate their expertise, authority, and accountability. This article argues that both UCS services' particular legitimacy problem (i.e., their possession of both private and public attributes) and the interactive nature of public legitimation work create tensions that may serve to disrupt UCS services' ability to attain legitimacy. Cet article examine la maniere dont les services de securite d'entreprise a l'universite (SEU) s'engagent a legitimer leurs tentatives de persuader leurs communautes universitaires (c'est-a-dire le corps professoral, le personnel et les etudiants) ainsi que la haute administration (c'est-a-dire les administrateurs de l'universite, le conseil des gouverneurs et les senateurs) qu'ils sont honnetes, attentifs, dignes de confiance, et qu'ils possedent un niveau d'autorite auquel quiconque devrait se referer. Ceci sera accompli en analysant un corpus d'entrevues et d'observations dans le cadre d'un projet de recherche examinant les services de type SEU dans cinq universites canadiennes, ainsi qu'une etude sur la maniere dont les services de SEU dans quatorze universites canadiennes gerent leurs communications sur le reseau de medias sociaux Twitter. Il a ete etabli que ces services de SEU utilisent principalement Twitter pour la sollicitation ou la demande d'informations, et pour le reseautage. En communiquant par Twitter, les services de SEU s'engagent dans un processus de legitimation par lequel ils revendiquent et tentent de demontrer leur expertise, autorite, transparence et responsabilite. Cet article propose l'argument suivant: la question de la legitimite particuliere des services de SEU (c'est-a-dire leur possession d'attributs a la fois prives et publics) combinee avec la nature interactive du processus de legitimation publique cree des tensions qui peuvent en fin de compte perturber la capacite des services de SEU a atteindre reellement cette legitimite. PMID- 27183967 TI - Critical Nexus or Chaotic Discipline? Re-Visioning Sociology Again. PMID- 27183968 TI - Agonist and antagonist bind differently to 5-HT1A receptors during Alzheimer's disease: A post-mortem study with PET radiopharmaceuticals. AB - PET imaging studies using 5-HT1A receptor radiotracers show a decreased density of this receptor in hippocampi of patients with Alzheimer's disease (AD) at advanced stages. However, current 5-HT1A receptor radiopharmaceuticals used in neuroimaging are antagonists, thought to bind to 5-HT1A receptors in different functional states (i.e., both the one which displays high affinity for agonists and is thought to mediate receptor activation, as well as the state which has low affinity for agonists). Comparing the PET imaging obtained using an agonist radiotracer, which binds selectively to functional receptors, with the PET imaging obtained using an antagonist radiotracer would therefore provide original information on 5-HT1A receptor impairment during AD. Quantitative autoradiography using [(18)F]F13640 and [(18)F]MPPF, a 5-HT1A agonist and antagonist, respectively, was measured in hippocampi of patients with AD (n = 25, at different Braak stages) and control subjects (n = 9). The neuronal density was measured in the same tissues by NeuN immunohistochemistry. The specific binding of both radiotracers was determined by addition of WAY-100635, a selective 5-HT1A receptor antagonist. The autoradiography distribution of both 5-HT1A PET radiotracers varied across hippocampus regions. The highest binding density was in the pyramidal layer of CA1. Incubation with Gpp(NH)p, a non-hydrolysable analogue of GTP, reduced significantly [(18)F]F13640 binding in hippocampal regions, confirming its preferential interaction with G-coupled receptors, and slightly increased [(18)F]MPPF binding. In the CA1 subfield, [(18)F]F13640 binding was significantly decreased at Braak stages I/II (-19%), Braak stages III/IV (-23%), and Braak stages V/VI (-36%) versus control. In contrast, [(18)F]MPPF binding was statistically reduced only at the most advanced Braak stages V/VI compared to control (-33%). Since [(18)F]F13640 and [(18)F]MPPF can be used in vivo in humans, this neuropharmacological paradigm supports testing the concept of functional imaging using agonist radiopharmaceuticals in future clinical studies. PMID- 27183969 TI - A Fragmentary Archive: Migratory Feelings in Early Anglo-Saxon Women's Letters. AB - The letters by Anglo-Saxon women in the Boniface correspondence are connected by cultural practices and emotions centered on the conversion mission that functioned to maintain connections between the Anglo-Saxon diaspora. A striking recurring focus of these letters is on loss and isolation, which connects them to the Old English elegies. Many of the letters describe the writers' traumatic experiences that result from the death or absence of kin. These are women who endured the trauma of being left behind when others migrated overseas or who, in traveling away from their homeland, found themselves isolated in an alien environment, displaced in time as well as space. This article offers an analysis of the letters, focusing on the queer temporalities they explore, the queer emotions they evoke, and the queer kinships that they forge. It argues that the women's letters represent fragments of an early queer archive of migratory feelings. PMID- 27183970 TI - Efficacy and speed of kill of a topically applied formulation of dinotefuran permethrin-pyriproxyfen against weekly tick infestations with Rhipicephalus sanguineus (sensu lato) on dogs. AB - BACKGROUND: Rhipicephalus sanguineus (sensu lato) is a vector of canine babesiosis, anaplasmosis and ehrlichiosis. In order to reduce the chance of transmission of these diseases, an ectoparasiticide should rapidly repel or kill new infestations with this tick. The primary objective of the present study was to evaluate the treatment and preventive acaricidal efficacy of Vectra(r) 3D (54.45 mg/ml of dinotefuran, 396.88 mg/ml of permethrin and 4.84 mg/ml of pyriproxyfen) against R. sanguineus (s.l.) measured at 2, 8, and 48 h after treatment and weekly re-infestation. METHODS: Twenty-four dogs were each infested with 50 adult R. sanguineus (s.l.) on Day -7 and allocated to three groups (n = 8) based on tick counts: an untreated control group (Group 1), and two groups (Groups 2 and 3) treated with Vectra(r)3D. The dogs in each group were infested with 50 ticks on Day -2. Vectra(r)3D was administered topically to the dogs on Day 0. Ticks were counted, in situ at 2 and 8 h after treatment on dogs in Groups 1 and 3. Group 3 was then withdrawn from the study and ticks were counted and removed from the dogs in Groups 1 and 2, 48 h after treatment. On Days 7, 14, 21, 28, 35 and 42, the dogs in Groups 1 and 2 were re-infested with 50 ticks, which were then counted in situ at 2 and 8 h, and counted and removed at 48 h after re infestation. RESULTS: Ticks from the initial infestation were visually unaffected by 2 and 8 h after treatment. However, by 2 h after weekly re-infestation the arithmetic mean (AM) efficacy of Vectra(r) 3D from Days 7 through 28 ranged from 61.1 to 78.8 %, falling to 60.1 and 47.4 % on Days 35 and 42 respectively. By 8 h after weekly re-infestation, the AM efficacy ranged from 89.1 to 97.4 % falling to 81.4 and 69.8 % on Days 35 and 42 respectively. The AM efficacy 48 h after treatment after the initial infestation was 22.9 % but after weekly re infestation the efficacy at 48 h ranged from 89.1 to 100.0 %, falling to 86.0 and 81.1 % on Days 35 and 42 respectively. CONCLUSION: Vectra(r) 3D demonstrated significant efficacy against new infestations of adult R. sanguineus (s.l.) ticks within 2 h of infestation as compared to the untreated control group and achieved over 89.1 % efficacy within 8 h of infestation for up to 4 weeks after administration. These results indicate that Vectra(r) 3D has a rapid and significant efficacy against new infestations of adult R. sanguineus (s.l.) ticks and should therefore be considered as part of a strategy against important vector borne diseases in dogs. PMID- 27183971 TI - The inner state differences of preterm birth rates in Brazil: a time series study. AB - BACKGROUND: Preterm birth is a serious public health problem, as it is linked to high rates of neonatal and child morbidity and mortality. The prevalence of premature births has increased worldwide, with regional differences. The objective of this study was to analyze the trend of preterm births in the state of Parana, Brazil, according to Macro-regional and Regional Health Offices (RHOs). METHODS: This is an ecological time series study using preterm births records from the national live birth registry system of Brazil's National Health Service - Live Birth Information System (Sinasc), for residents of the state of Parana, Brazil, between 2000 and 2013. The preterm birth rates was calculated on a yearly basis and grouped into three-year periods (2000-2002, 2003-2005, 2006 2008, 2009-2011) and one two-year period (2012-2013), according to gestational age and mother's Regional Health Office of residence. The polynomial regression model was used for trend analysis. RESULTS: The predominance of preterm birth rate increased from 6.8 % in 2000 to 10.5 % in 2013, with an average increase of 0.20 % per year (r(2) = 0.89), and a greater share of moderate preterm births (32 to <37 weeks), which increased from 5.8 % to 9 %. The same pattern was observed for all Macro-regional Health Offices, with highlight to the Northern Macro Regional Office, which showed the highest average rate of prematurity and average annual growth during that period (7.55 % and 0.35 %, respectively). The trend analysis of preterm birth rates according to RHO showed a growing trend for almost all RHOs - except for the 7(th) RHO where a declining trend was observed ( 0.95 a year); and in the 20(th), 21(st) and 22(nd) RHOs which remained unchanged. In the last three-year of the study period (2011-2013), no RHO showed preterm birth rates below 7.3 % or prevalence of moderate preterm birth below 9.4 %. CONCLUSIONS: The results show an increase in preterm births with differences among Macro-regional and RHOs, which indicate the need to improve actions during the prenatal period according to the specificities of each region. PMID- 27183973 TI - Response of the protistan community of a rice field soil to different oxygen tensions. AB - Heterotrophic protists in soil are grazers that control the biomass and community structure of bacteria, thereby enhancing nutrient recycling. Oxygen regulates the microeukaryotic community, but little is known about its response to microoxic conditions. Here we studied the impact of oxygen tension on culturable heterotrophic protists in a rice field soil. The number of protists, dominated by amoeba and flagellates, under oxygen tensions ranging from atmospheric level (21%) to below the Pasteur point (0.08%) were similar (10(4) cells g(-1) dry soil); no protists were detected under anoxic conditions. DGGE fingerprinting of microeukaryotes demonstrated a shift in the community structure depending on the oxygen tension during growth. Both common and specific amoeba and flagellates were identified at different oxygen tensions. Amoeba isolates (Acanthamoeba sp. and Hartmannella sp.) grew to the same extent under the oxygen tensions tested; the Acanthamoeba sp. isolate migrated more slowly under the lowest tension (0.08%). Our results demonstrated that amoeba and flagellates in soil adapt to a wide range of oxygen tensions with a shift in community structure. This suggests an ability to search for food in soil environments such as the oxic-anoxic interface of flooded soil or inside soil aggregates that are inaccessible to ciliates. PMID- 27183972 TI - Knowledge about electronic cigarettes and its perception: a community survey, Egypt. AB - BACKGROUND: Electronic cigarettes are promoted as safer products than traditional cigarettes and as smoking cessation devices. Awareness and perception are key elements for the adoption of new habits. Little is known about electronic cigarettes and public opinions towards it. This study aims to identify the prevalence of knowledge about electronic cigarettes, its perception, and use among Egyptian population. METHODS: An observational cross-sectional study using self-administered questionnaire in Arabic language was conducted between March and April 2015 among a sample of Egyptian population aged 15-75 years (N = 1239). We compared between respondent's who know e-cigarettes and those who do not know it. RESULTS: More than half (57.5 %) of the respondents had heard about e cigarettes, 51.8 % were non-smokers and nobody of them reported use of e cigarettes. There were statistically significant differences between those who know and those who do not know e-cigarettes regarding age, educational levels and history of smoking. Among those who know e-cigarettes, 41.6 % believed that e cigarettes help smoking cessation and 31.9 % believed it is less harmful than traditional cigarettes. CONCLUSIONS: A considerable level of knowledge about e cigarettes is found among young people aged 15-39 years. E-cigarettes were perceived as less harmful than traditional cigarettes or a smoking cessation aid. None of the respondents reported use of e-cigarettes. PMID- 27183974 TI - Effects of inter and intraspecific diversity and genetic divergence of aquatic fungal communities on leaf litter decomposition-a microcosm experiment. AB - Freshwater fungi play a key role in plant litter decomposition and have been used to investigate the relationships between biodiversity and ecosystem functioning in streams. Although there is evidence of positive effects of biodiversity on ecosystem processes, particularly on biomass produced, some studies have shown that neutral or negative effects may occur. We manipulated the composition and the number of species and genotypes in aquatic fungal assemblages creating different levels of genetic divergence to assess effects of fungal diversity on biomass produced and leaf decomposition. Generally, diversity effects on fungal biomass produced were positive, suggesting complementarity between species, but in assemblages with more species positive diversity effects were reduced. Genotype diversity and genetic divergence had net positive effects on leaf mass loss, but in assemblages with higher diversity leaf decomposition decreased. Our results highlight the importance of considering multiple biodiversity measures when investigating the relationship between biodiversity and ecosystem functioning. PMID- 27183975 TI - The Effect of Breakfast Type on Total Daily Energy Intake and Body Mass Index Among Thai School Children. AB - The study investigated the association between breakfast types consumed, daily energy intake, and body mass index for age Z-score (BAZ). Cross-sectional data from 1258 children aged 7 to 12.9 years were analyzed for breakfast type, nutrient intakes, BAZ, and proportion of overweight or obesity. Analysis of covariance was used to compare energy and nutrient intakes, BAZ, and proportion of overweight/obese children between breakfast groups. Only 19% of children had adequate energy intake from breakfast. Those consuming snacks had a significantly lower BAZ (Z = -0.73), with 5% of them being overweight/obese. Those consuming beverages and desserts had the lowest total daily energy intake (1314 kcal) and lowest protein intake (8.4 g). The results suggest that breakfast type is associated with daily energy intake and BAZ. Most breakfasts are not adequate. School-based nutrition education programs involving families, teachers, and health professionals can contribute to improve this situation. PMID- 27183976 TI - Serological Prevalence of Leptospirosis Among Rural Communities in the Rejang Basin, Sarawak, Malaysia. AB - Leptospirosis is an important zoonotic disease globally and is endemic in Malaysia. A study was conducted in the Rejang basin of Sarawak from June 2011 to May 2013 to determine the seroprevalence of leptospirosis among the communities and dominant infecting Leptospira serovars. A total of 508 human sera were analyzed using ELISA and the microscopic agglutination test (MAT). The seroprevalence of leptospirosis in the study area was 37.4%, with the highest prevalence in Kapit division. More women were positive for leptospirosis (59.5%), and the mean age of seropositive individuals was 42.2 (SD = 18.7) years. Antibody titers between 1:50 and 1:1600 were reported, and serovars djasiman (22.1%), shermani (13.2%), and pomona (7.9%) predominated, with varied distribution between geographical locations. This study highlighted the endemicity and diversity of existing Leptospira serovars within the community. This information should be communicated to local health personnel and communities at risk, and rapid diagnostic capability should be made available to local health facilities. PMID- 27183977 TI - Invasive meningococcal disease in three siblings with hereditary deficiency of the 8(th) component of complement: evidence for the importance of an early diagnosis. AB - BACKGROUND: Deficiency of the eighth component of complement (C8) is a very rare primary immunodeficiency, associated with invasive, recurrent infections mainly caused by Neisseria species. We report functional and immunochemical C8 deficiency diagnosed in three Albanian siblings who presented with severe meningococcal infections at the age of 15 years, 4 years and 17 months, respectively. The youngest suffered serious complications (necrosis of fingers and toes requiring amputation). METHODS: Functional activity of the classical, alternative and mannose-binding lectin complement pathways was measured in serum from the 3 siblings and their parents (37-year-old woman and 42-year-old man). Forty healthy subjects (20 males and 20 females aged 4-38 years) served as normal controls. Serum complement factors were measured by haemolytic assays and immunoblotting. Sequence DNA analysis of the C8B gene was performed. RESULTS: Analyses of the three complement pathways revealed no haemolytic activity and also absence of C8beta in serum samples from all three siblings. The genetic analysis showed that the three siblings were homozygous for the p.Arg428* mutation in the C8B gene on chromosome 1p32 (MIM 120960). The parents were heterozygous for the mutation and presented normal complement activities. A 2 year follow-up revealed no further infective episodes in the siblings after antibiotic prophylaxis and meningococcal vaccination. CONCLUSIONS: Complement deficiencies are rare and their occurrence is often underestimated. In presence of invasive meningococcal infection, we highlight the importance of complement screening in patients and their relatives in order to discover any genetic defects which would render necessary prophylaxis to prevent recurrent infections and severe complications. PMID- 27183978 TI - Transmasculine individuals' experiences with lactation, chestfeeding, and gender identity: a qualitative study. AB - BACKGROUND: Transmasculine individuals are people who were assigned as female at birth, but identify on the male side of the gender spectrum. They might choose to use and engage their bodies to be pregnant, birth a baby, and chestfeed. This study asked an open research question, "What are the experiences of transmasculine individuals with pregnancy, birthing, and feeding their newborns?" METHODS: Participants who self-identified as transmasculine and had experienced or were experiencing pregnancy, birth, and infant feeding were recruited through the internet and interviewed. Interviews were transcribed verbatim. We used interpretive description methodology to analyze the data. Our analysis was guided by our awareness of concepts and history important to the transgender community. RESULTS: Out of 22 participants, 16 chose to chestfeed for some period of time, four participants did not attempt chestfeeding, and two had not reached the point of infant feeding (i.e., were still pregnant or had a miscarriage). Nine of the 22 study participants had chest masculinization surgery before conceiving their babies. Six participants had the surgery after their children were born, five desired the surgery in the future, and two did not want it at all. Chest care, lactation, and chestfeeding in the context of being a transgender person are reported in this paper. The participants' experiences of gender dysphoria, chest masculinization surgery before pregnancy or after weaning, accessing lactation care as a transmasculine person, and the question of restarting testosterone emerged as data. We present the participants' experiences in a chronological pattern with the categories of before pregnancy, pregnancy, postpartum (6 weeks post birth), and later stage (beyond 6 weeks). CONCLUSIONS: The majority of participants chose to chestfeed while some did not due to physical or mental health reasons. Care providers should communicate an understanding of gender dysphoria and transgender identities in order to build patient trust and provide competent care. Further, health care providers need to be knowledgeable about lactation and chest care following chest masculinization surgery and during binding, regardless of the chosen feeding method and through all stages: before pregnancy, during pregnancy, postpartum, and afterward. PMID- 27183980 TI - The Use of Stilbene Scaffold in Medicinal Chemistry and Multi- Target Drug Design. AB - The stilbene scaffold is a basic element for a number of biologically active natural and synthetic compounds, and it is considered as a privileged structure. Stilbenes exemplified by resveratrol, combretastatin A-4 and pterostilbene are of significant interest for drug research and development because of their potential in therapeutic and preventive application. Resveratrol, present in grapes and other food products, plays a role in the prevention of several human pathological processes and has been suggested as an anticancer agent. Moreover, recent evidence has revealed its potential effect on the aging process, diabetes and neurological dysfunction. Combretastatin A-4, from the bark of South African bush willow Combretum caffrum, also shows significant antitumor activity. Pterostilbene is closely related to resveratrol, sharing the same unique therapeutic potential as anti-inflammatory, antineoplastic and antioxidant agent. Therefore, research and development of stilbene-based medicinal chemistry have become rapidly evolving and increasingly active topics covering almost the whole range of therapeutic fields. In the present review, we provide an overview of the role of stilbenes in medicinal chemistry. In this context, we highlight the chemical methodologies adopted for the synthesis of stilbene derivatives, and outline the successful design of novel stilbene based hybrids in the field of cancer, Alzheimer's and other relevant diseases. This information may be useful in further design of stilbene-based molecules as new leads for the development of novel agents with clinical potential or as effective chemical probes to dissect biological processes. PMID- 27183979 TI - Transcriptome analysis reveals self-incompatibility in the tea plant (Camellia sinensis) might be under gametophytic control. AB - BACKGROUND: Self-incompatibility (SI) is under genetic control and prevents inbreeding depression in angiosperms. SI mechanisms are quite complicated and still poorly understood in many plants. Tea (Camellia sinensis L.) belonging to the family of Theaceae, exhibits high levels of SI and high heterozygosity. Uncovering the molecular basis of SI of the tea plant may enhance breeding and simplify genomics research for the whole family. RESULTS: The growth of pollen tubes following selfing and crossing was observed using fluorescence microscopy. Self-pollen tubes grew slower than cross treatments from 24 h to 72 h after pollination. RNA-seq was employed to explore the molecular mechanisms of SI and to identify SI-related genes in C. sinensis. Self and cross-pollinated styles were collected at 24 h, 48 h and 72 h after pollination. Six RNA-seq libraries (SP24, SP48, SP72, CP24 CP48 and CP72; SP = self-pollinated, CP = cross pollinated) were constructed and separately sequenced. In total, 299.327 million raw reads were generated. Following assembly, 63,762 unigenes were identified, and 27,264 (42.76 %) unigenes were annotated in five public databases: NR, KOG, KEGG, Swiss-Port and GO. To identify SI-related genes, the fragments per kb per million mapped reads (FPKM) values of each unigene were evaluated. Comparisons of CP24 vs. SP24, CP48 vs. SP48 and CP72 vs. SP72 revealed differential expression of 3,182, 3,575 and 3,709 genes, respectively. Consequently, several ubiquitin mediated proteolysis, Ca(2+) signaling, apoptosis and defense-associated genes were obtained. The temporal expression pattern of genes following CP and SP was analyzed; 6 peroxidase, 1 polyphenol oxidase and 7 salicylic acid biosynthetic process-related genes were identified. The RNA-seq data were validated by qRT-PCR of 15 unigenes. Finally, a unigene (CL25983Contig1) with strong homology to the S RNase was analyzed. It was mainly expressed in styles, with dramatically higher expression in self-pollinated versus cross-pollinated tissues at 24 h post pollination. CONCLUSIONS: The present study reports the transcriptome of styles after cross- and self-pollination in tea and offers novel insights into the molecular mechanism behind SI in C. sinensis. We believe that this RNA-seq dataset will be useful for improvement in C. sinensis as well as other plants in the Theaceae family. PMID- 27183981 TI - Recent Trends in the Discovery of Small Molecule Blockers of Sodium Channels. AB - Voltage-gated sodium channels (VGSC) are responsible for the selective influx of sodium ions in excitable cells. A number of physiological phenomena such as muscle contraction, pain sensation, processing of neuronal information in the brain as well as neuronal regulation of peripheral tissues rely on the activity of these channels. On the other hand, abnormal activity of VGSC are implicated in several pathological processes (e.g., cardiac arrhythmias, epilepsy, and chronic pain) which in some cases (e.g., channelopathies such as myotonias) are linked to specific gene mutations. As a result, VGSC have never stopped attracting the attention of medicinal chemists and the quest for novel drugs to treat these ion channels-associated diseases continues. In this review, VGSC blocking agents reported in the last lustrum are scrutinised with the aim to give a medicinal chemistry perspective on the most interesting compounds classified on the basis of (i) potential therapeutic application, (ii) targeted VGSC isoforms, and (iii) chemical scaffolds. Finally, the clinical potential of selected drug candidates from each chemotype is evaluated by comparing their ligand efficiency metrics. Possible routes for improvement of these preclinical candidates are also discussed. PMID- 27183982 TI - Naturally Occurring Wound Healing Agents: An Evidence-Based Review. AB - Nature constitutes a pool of medicines for thousands of years. Nowadays, trust in nature is increasingly growing, as many effective medicines are naturally derived. Over the last decades, the potential of plants as wound healing agents is being investigated. Wounds and ulcers affect the patients' life quality and often lead to amputations. Approximately 43,000,000 patients suffer from diabetic foot ulcers worldwide. Annually, $25 billion are expended for the treatment of chronic wounds, with the number growing due to aging population and increased incidents of diabetes and obesity. Therefore a timely, orderly and effective wound management and treatment is crucial. This paper aims to systematically review natural products, mainly plants, with scientifically well documented wound healing activity, focusing on articles based on animal and clinical studies performed worldwide and approved medicinal products. Moreover, a brief description of the wound healing mechanism is presented, to provide a better understanding. Although a plethora of natural products are in vitro and in vivo evaluated for wound healing activity, only a few go through clinical trials and even fewer launch the market as approved medicines. Most of them rely on traditional medicine, indicating that ethnopharmacology is a successful strategy for drug development. Since only 6% of plants have been systematically investigated pharmacologically, more intensified efforts and emerging advancements are needed to exploit the potentials of nature for the development of novel medicines. This paper aims to provide a reliable database and matrix for thorough further investigation towards the discovery of wound healing agents. PMID- 27183983 TI - Antiarrhythmic Mexiletine: A Review on Synthetic Routes to Racemic and Homochiral Mexiletine and its Enantioseparation. AB - Mexiletine is an oral class IB antiarrhythmic agent. Although it was primarily studied for the treatment of ventricular arrhythmias, it has been demonstrated to be useful also for the treatment of chronic painful diabetic neuropathy, neuropathic pain, skeletal muscle channelopathies, and recently amyotrophic lateral sclerosis. This review presents a detailed report on the different synthetic routes to racemic and homochiral mexiletine developed in the last decades, as well as analytical studies regarding enantioseparation methods and enantiomeric excess determination. Finally, some analogues of mexiletine reported in the literature, most of which along with pharmacological studies, have been mentioned. PMID- 27183984 TI - G-Quadruplex Aptamers to Human Thrombin Versus Other Direct Thrombin Inhibitors: The Focus on Mechanism of Action and Drug Efficiency as Anticoagulants. AB - Thrombin is a key enzyme of blood coagulation system which has multiple functions including pro- and anticoagulant, platelet aggregating and inflammatory activities. Unsurprisingly, this enzyme has been a target for anticoagulant drug development for decades. Among the most interesting direct thrombin inhibitors with intravenous administration route are the following ones: 1) hirudins, proteins with bivalent binding mode to the thrombin, 2) bivalirudin, the peptide with bivalent binding mode to the thrombin, 3) argatroban, the chemical that binds to the thrombin active site, and 4) G-quadruplex DNA aptamers, structured oligonucleotides with an affinity to protein-binding site of the thrombin. Efficiency of all these inhibitors has been studied in vivo in preclinical and clinical trials, as well as in vitro with various tests, allowing to compare them thoroughly. In the review three levels of comparison were used to highlight the features of each inhibitor: 1) thrombin inhibition constants as a characteristic of inhibitor potency in simple enzymatic system; 2) inhibition of fibrin fiber formation and thrombin generation in coagulation cascade as a characteristic of anticoagulant potency in human blood plasma; and 3) therapeutic doses used and therapeutic profiles obtained after intravenous administration into animals and humans. The data clearly demonstrate weak and strong aspects of thrombin binding aptamers providing a solid background for further novel anticoagulant development.

15.5 U/L. With the application of this threshold, raised GGT levels had 83% sensitivity (95% CI 0.70-0.90) and 67.5% specificity (95% CI 0.52-0.79), for the diagnosis of PCOS. In our study, GGT levels were elevated in the PCOS patients independent of BMI and could thus be an important marker of PCOS. PMID- 27183993 TI - Is surgery still the optimal treatment for stage I non-small cell lung cancer? AB - There is debate about what is the optimal treatment for operable stage I non small cell lung cancer (NSCLC). Although surgery has been the standard of care for centuries, recent retrospective and prospective randomized studies indicated that stereotactic ablative radiotherapy (SABR) could be an option for this group of patients with similar survival and less toxicities. However, to change the standard of care, more studies are needed and participating ongoing larger randomized studies is the best approach to resolve this controversy. PMID- 27183994 TI - Production of high concentration of L-lactic acid from cellobiose by thermophilic Bacillus coagulans WCP10-4. AB - Thermophilic Bacillus coagulans WCP10-4 is found to be able to convert cellobiose to optically pure L-lactic acid. Its beta-glucosidase activity is detected in whole cells (7.3 U/g dry cells) but not in culture medium, indicating the intracellular location of the enzyme. Its beta-glucosidase activity is observed only when cultured using cellobiose as the sole carbon source, indicating that the expression of this enzyme is tightly regulated in cells. The enzyme is most active at 50 degrees C and pH 7.0. The supplement of external beta-glucosidase during fermentation of cellobiose (106 g/l) by B. coagulans WCP10-4 increased the fermentation time from 21 to 23 h and decreased the lactic acid yield from 96.1 to 92.9 % compared to the control without beta-glucosidase supplementation. B. coagulans WCP10-4 converted 200 g/l of cellobiose to 196.3 g/l of L-lactic acid at a yield of 97.8 % and a productivity of 7.01 g/l/h. This result shows that B. coagulans WCP10-4 is a highly efficient strain for converting cellobiose to L lactic acid without the need of supplementing external beta-glucosidases. PMID- 27183996 TI - Identification and characterization of a long-chain fatty acid transporter in the sophorolipid-producing strain Starmerella bombicola. AB - The sophorolipid-producing strain Starmerella bombicola CGMCC 1576 has a remarkable ability to produce sophorolipids (SLs) under the acidic and lactonic forms with almost equal proportion. In this study, we found the gene encoding for the long-chain acyl-CoA synthetase (ALCS). This enzyme was putatively identified as a membrane-bound long-chain fatty acid transport protein and contributed to the uptake of long-chain fatty acids. Disruption of the alcs gene resulted in an impaired growth of the alcs-deleted mutant in minimal media containing different fatty acids (C12:0, C14:0, C16:0, C18:0, C22:0, and C24:0) as the sole carbon source and led to a dramatic decrease in the uptake of the fluorescent-tagged long-chain fatty acid analogue-boron dipyrromethene difluoride dodecanoic acid (BODIPY-3823). The absence of this alcs gene caused obvious phenotype changes. Compared with the wild-type strain, the yield and compositions of the SLs produced by the gene-deleted mutant of ?alcs::six showed almost no lactonic form of SLs, and the acidic SLs were composed of medium-chain. The ALCS enzyme was heterologously expressed in Escherichia coli JM109 (DE3) with pMAL-c2x-alcs. The enzyme was purified through a maltose-binding protein (MBP) affinity chromatography column and was confirmed to be homogeneous by SDS-PAGE. The recombinant enzyme could catalyze the formation of the long-chain acyl-CoA when the long-chain fatty acids and the coenzyme A were used as substrates. PMID- 27183997 TI - Innate immune response, intestinal morphology and microbiota changes in Senegalese sole fed plant protein diets with probiotics or autolysed yeast. AB - The effects of using plant ingredients in Senegalese sole (Solea senegalensis) diet on immune competence and intestine morphology and microbial ecology are still controversial. Probiotics or immunostimulants can potentially alter the intestinal microbiota in a way that protects fish against pathogens. The current study aimed to examine the intestine histology and microbiota and humoral innate immune response in juvenile sole fed diets with low (35 %) or high (72 %) content of plant protein (PP) ingredients supplemented with a multispecies probiotic bacteria or autolysed yeast. Fish fed the probiotic diet had lower growth performance. Lysozyme and complement activities were significantly higher in fish fed PP72 diets than in their counterparts fed PP35 diets after 17 and 38 days of feeding. At 2 days of feeding, fish fed unsupplemented PP72 showed larger intestine section area and longer villus than fish fed unsupplemented PP35. At 17 days of feeding, fish fed unsupplemented PP72 showed more goblet cells than the other dietary groups, except the group fed yeast supplemented PP35 diet. High dietary PP level, acutely stimulate fish innate immune defence of the fish after 2 and 17 days of feeding. However, this effect does not occur after 73 days of feeding, suggesting a habituation to dietary treatments and/or immunosuppression, with a reduction in the number of the goblet cells. Fish fed for 38 days with diets supplemented with autolysed yeast showed longer intestinal villus. The predominant bacteria found in sole intestine were Vibrio sp. and dietary probiotic supplementation caused a reduction in Vibrio content, regardless of the PP level. PMID- 27183998 TI - Effects of volatile organic compounds produced by Bacillus amyloliquefaciens on the growth and virulence traits of tomato bacterial wilt pathogen Ralstonia solanacearum. AB - The production of volatile organic compounds (VOCs) by microbes is an important characteristic for their selection as biocontrol agents against plant pathogens. In this study, we identified the VOCs produced by the biocontrol strain Bacillus amyloliquefaciens T-5 and evaluated their impact on the growth and virulence traits of tomato bacterial wilt pathogen Ralstonia solanacearum. The results showed that the VOCs of strain T-5 significantly inhibited the growth of R. solanacearum in agar medium and in soil. In addition, VOCs significantly inhibited the motility traits, root colonization, biofilm formation, and production of antioxidant enzymes and exopolysaccharides by R. solanacearum. However, no effect of VOCs on the production of hydrolytic enzymes by R. solanacearum was observed. The strain T-5 produced VOCs, including benzenes, ketones, aldehydes, alkanes, acids, and one furan and naphthalene compound; among those, 13 VOCs showed 1-10 % antibacterial activity against R. solanacearum in their produced amounts by T-5; however, the consortium of all VOCs produced on agar medium, in sterilized soil, and in natural soil showed 75, 62, and 85 % growth inhibition of R. solanacearum, respectively. The real-time PCR analysis further confirmed the results when the expression of different virulence- and metabolism-related genes in R. solanacearum cells was decreased after exposure to the VOCs of strain T-5. The results of this study clearly revealed the significance of VOCs in the control of plant pathogens. This information would help to better comprehend the microbial interactions mediated by VOCs in nature and to develop safer strategies to control plant disease. PMID- 27183995 TI - Ploidy influences the functional attributes of de novo lager yeast hybrids. AB - The genomes of hybrid organisms, such as lager yeast (Saccharomyces cerevisiae * Saccharomyces eubayanus), contain orthologous genes, the functionality and effect of which may differ depending on their origin and copy number. How the parental subgenomes in lager yeast contribute to important phenotypic traits such as fermentation performance, aroma production, and stress tolerance remains poorly understood. Here, three de novo lager yeast hybrids with different ploidy levels (allodiploid, allotriploid, and allotetraploid) were generated through hybridization techniques without genetic modification. The hybrids were characterized in fermentations of both high gravity wort (15 degrees P) and very high gravity wort (25 degrees P), which were monitored for aroma compound and sugar concentrations. The hybrid strains with higher DNA content performed better during fermentation and produced higher concentrations of flavor-active esters in both worts. The hybrid strains also outperformed both the parent strains. Genome sequencing revealed that several genes related to the formation of flavor-active esters (ATF1, ATF2 EHT1, EEB1, and BAT1) were present in higher copy numbers in the higher ploidy hybrid strains. A direct relationship between gene copy number and transcript level was also observed. The measured ester concentrations and transcript levels also suggest that the functionality of the S. cerevisiae- and S. eubayanus-derived gene products differs. The results contribute to our understanding of the complex molecular mechanisms that determine phenotypes in lager yeast hybrids and are expected to facilitate targeted strain development through interspecific hybridization. PMID- 27183999 TI - Multi-breed genome-wide association study reveals heterogeneous loci associated with loin eye area in pigs. AB - Numerous quantitative trait loci (QTL) for loin eye area had been identified by linkage mapping studies, but the lack of their precise position hinders their application in the pig breeding industry. To map QTL for loin eye area to a precise genomic region, we conducted a genome-wide association study (GWAS) using Illumina 60 K PorcineSNP60 Beadchip in four swine populations: 819 F2 pigs, 273 Laiwu pigs, 434 Sutai pigs, and 326 Erhualian pigs. In total, 26 single nucleotide polymorphisms (SNPs) deposited on seven chromosomes associated with loin eye area were identified, 11 of which surpassed the genome-wide significant threshold; of the 11 SNPs, seven located on SSC2 in F2 pigs and four located on SSC12 and SSC18 in Laiwu pigs. Of note, all of the identified QTL were breed specific and no common QTL was identified across the four populations in our study. These findings not only confirmed a previous QTL on SSC2 harboring the candidate gene insulin-like growth factor 2 (IGF2), but also identified some novel candidate genes, far upstream element binding protein 3 (FUBP3), myosin heavy chain (MYH) family, leucine-rich repeats and guanylate kinase domain containing (LRGUK). Our study will contribute to the further identification of the causal mutation underlying these QTL and improve our knowledge of the complex genetic architecture for loin eye area in pigs. PMID- 27184000 TI - Binding, Antioxidant and Anti-proliferative Properties of Bioactive Compounds of Sweet Paprika (Capsicum annuum L.). AB - The scope of this research was to determine the bioactive composition, antioxidant, binding, and anti-proliferative properties of red sweet paprika growing under artificial light. The amounts of carotenoids, chlorophyll, polyphenols, tannins, and flavonoids in red paprika (RP), cultivated in Korea, before and after light treatments under high pressure sodium (HPS) and lighting emitting plasma (LEP) lamps (RPControl, RPHPS, RPLEP), were analyzed in water (W) and ethanolic extracts (Et). Spectroscopic, radical scavenging assays, fluorescence and cytotoxicity measurements were applied. The results of this study showed that total chlorophyll and carotenes were the highest in RPHPS (10.50 +/- 1.02 and 33.90 +/- 3.26 MUg/g dry weight (DW)). The strongest antioxidant capacity (MUM TE/g DW) in a 2, 2'-azino-bis (3-ethyl-benzothiazoline 6-sulfonic acid) diammonium salt (ABTS(*+)) assay was in RPControlEt (24.34 +/- 2.36), in a ferric-reducing/antioxidant power (FRAP) assay in RPHPSW (27.08 +/- 2.4) and in a cupric reducing antioxidant (CUPRAC) in RPLEPW (70.99 +/- 7.11). The paprika ethanolic extracts showed lower values in their bioactivity than the water ones. The binding and cytotoxicity abilities of extracted polyphenols correlated with their amounts. LEP treatment is better for plant growth characteristics than other conventional treatments. The investigated paprika samples can be used as a source of antioxidants. PMID- 27184003 TI - First-principle investigation on growth patterns and properties of cobalt-doped lithium nanoclusters. AB - A systematic theoretical investigation on cobalt lithium clusters LinCo [1-12] was performed with a DFT approach. The location of global minima and structural evolution were carried out using the partical swarm optimization method. Li6Co is the transition structure in going from low-coordinated structures to three dimensional torispherical structures with a cobalt atom enclosed by lithium atoms. Maxima of ?2 E and E b for LinCo were found at n = 3, 6, 8, 10, indicating that these clusters possess higher relative stability than their neighbors. In comparison with small clusters, n = 1-6, the greater electron transfer from Li-2s to Co-3d within cage-like clusters LinCo (n = 7-12) strengthens the bonding effect between Lin and Co, which is reflected in the Wiberg bond index of Co and atomic binding energy analysis. AdNDP analysis verified the presence of both Lewis bonding elements (1c-2e objects) and delocalized bonding elements (6c-2e, 9c-2e and 10c-2e bonds). It is hoped that this theoretical work will provide favorable information to help understand the influence of dopant transition metal atoms on the properties of lithium-based materials. PMID- 27184002 TI - QM/MM investigation of the catalytic mechanism of angiotensin-converting enzyme. AB - Angiotensin-converting enzyme (ACE) converts angiotensin I to angiotensin II and degrades bradykinin and other vasoactive peptides. ACE inhibitors are used to treat diseases such as hypertension and heart failure. It is thus highly desirable to understand the catalytic mechanism of ACE, as this should facilitate the design of more powerful and selective ACE inhibitors. ACE exhibits two different active domains, the C-domain and the N-domain. In this work, we systematically investigated the inhibitor- and substrate-binding patterns in the N-domain of human ACE using a combined quantum mechanical and molecular mechanical approach. The hydrolysis of hippuryl-histidyl-leucine (HHL) as catalyzed by the N-domain of human somatic ACE was explored, and the effects of chloride ion on the overall reaction were also investigated. Two models, one with and one without a chloride ion at the first binding position, were then designed to examine the chloride dependence of inhibitor-substrate binding and the catalytic mechanism. Our calculations indicate that the hydrolysis reaction follows a stepwise general base/general acid catalysis path. The estimated mean free energy barrier height in the two models is about 15.6 kcal/mol, which agrees very well with the experimentally estimated value of 15.8 kcal/mol. Our simulations thus suggest that the N-domain is in a mixed form during ACE catalyzed hydrolysis, with the single-chloride-ion and the double-chloride-ion forms existing simultaneously. Graphical Abstract Superposition of ACE C- and N- domains. PMID- 27184001 TI - Indoor Allergens and Allergic Respiratory Disease. AB - PURPOSE OF REVIEW: The purpose of this review is to evaluate the most recent findings on indoor allergens and their impact on allergic diseases. RECENT FINDINGS: Indoor allergens are present inside buildings (home, work environment, school), and given the chronic nature of the exposures, indoor allergies tend to be associated with the development of asthma. The most common indoor allergens are derived from dust mites, cockroaches, mammals (including wild rodents and pets), and fungi. The advent of molecular biology and proteomics has led to the identification, cloning, and expression of new indoor allergens, which have facilitated research to elucidate their role in allergic diseases. This review is an update on new allergens and their molecular features, together with the most recent reports on their avoidance for allergy prevention and their use for diagnosis and treatment. Research progress on indoor allergens will result in the development of new diagnostic tools and design of coherent strategies for immunotherapy. PMID- 27184004 TI - Formation of the Si-B bond: insertion reactions of silylenes into B-X(X = F, Cl, Br, O, and N) bonds. AB - The insertion reactions of the silylene H2Si with H2BXHn-1 (X = F, Cl, Br, O, N; n = 1, 1, 1, 2, 3) have been studied by DFT and MP2 methods. The calculations show that the insertions occur in a concerted manner, forming H2Si(BH2)(XHn-1). The essences of H2Si insertions with H2BXHn-1 are the transfers of the sigma electrons on the Si atom to the positive BH2 group and the electrons of X into the empty p orbital on the Si atom in H2Si. The order of reactivity in vacuum shows the barrier heights increase for the same-family element X from up to down and the same-row element X from right to left in the periodic table. The energies relating to the B-X bond in H2BXHn-1, and the bond energies of Si-X and Si-B in H2Si(BH2)(XHn-1) may determine the preference of insertions of H2Si into B-X bonds for the same-column element X or for the same-row element X. The insertion reactions in vacuum are similar to those in solvents, acetone, ether, and THF. The barriers in vacuum are lower than those in solvents and the larger polarities of solvents make the insertions more difficult to take place. Both in vacuum and in solvents, the silylene insertions are thermodynamically exothermic. Graphical Abstract The insertion process of H2Si and H2BXHn-1(X = F, Cl, Br, O, and N; n = 1, 1 , 1, 2, 3). PMID- 27184005 TI - Cuticle lipids on heteromorphic leaves of Populus euphratica Oliv. growing in riparian habitats differing in available soil moisture. AB - Populus euphratica is an important native tree found in arid regions from North Africa and South Europe to China, and is known to tolerate many forms of environmental stress, including drought. We describe cuticle waxes, cutin and cuticle permeability for the heteromorphic leaves of P. euphratica growing in two riparian habitats that differ in available soil moisture. Scanning electron microscopy revealed variation in epicuticular wax crystallization associated with leaf type and site. P. euphratica leaves are dominated by cuticular wax alkanes, primary-alcohols and fatty acids. The major cutin monomers were 10,16-diOH C16:0 acids. Broad-ovate leaves (associated with adult phase growth) produced 1.3- and 1.6-fold more waxes, and 2.1- and 0.9-fold more cutin monomers, than lanceolate leaves (associated with juvenile phase growth) at the wetter site and drier site, respectively. The alkane-synthesis-associated ECERIFERUM1 (CER1), as well as ABC transporter- and elongase-associated genes, were expressed at much higher levels at the drier than wetter sites, indicating their potential function in elevating leaf cuticle lipids in the dry site conditions. Higher cuticle lipid amounts were closely associated with lower cuticle permeability (both chlorophyll efflux and water loss). Our results implicate cuticle lipids as among the xeromorphic traits associated with P. euphratica adult-phase broad-ovate leaves. Results here provide useful information for protecting natural populations of P. euphratica and their associated ecosystems, and shed new light on the functional interaction of cuticle and leaf heterophylly in adaptation to more arid, limited-moisture environments. PMID- 27184006 TI - Medication errors room: a simulation to assess the medical, nursing and pharmacy staffs' ability to identify errors related to the medication-use system. AB - RATIONALE, AIMS AND OBJECTIVES: The medication-use system in hospitals is very complex. To improve the health professionals' awareness of the risks of errors related to the medication-use system, a simulation of medication errors was created. The main objective was to assess the medical, nursing and pharmacy staffs' ability to identify errors related to the medication-use system using a simulation. The secondary objective was to assess their level of satisfaction. METHOD: This descriptive cross-sectional study was conducted in a 500-bed mother and-child university hospital. A multidisciplinary group set up 30 situations and replicated a patient room and a care unit pharmacy. All hospital staff, including nurses, physicians, pharmacists and pharmacy technicians, was invited. Participants had to detect if a situation contained an error and fill out a response grid. They also answered a satisfaction survey. RESULTS: The simulation was held during 100 hours. A total of 230 professionals visited the simulation, 207 handed in a response grid and 136 answered the satisfaction survey. The participants' overall rate of correct answers was 67.5% +/- 13.3% (4073/6036). Among the least detected errors were situations involving a Y-site infusion incompatibility, an oral syringe preparation and the patient's identification. Participants mainly considered the simulation as effective in identifying incorrect practices (132/136, 97.8%) and relevant to their practice (129/136, 95.6%). Most of them (114/136; 84.4%) intended to change their practices in view of their exposure to the simulation. CONCLUSIONS: We implemented a realistic medication-use system errors simulation in a mother-child hospital, with a wide audience. This simulation was an effective, relevant and innovative tool to raise the health care professionals' awareness of critical processes. PMID- 27184008 TI - The crucial role of FBXO28 in the pathogenesis of the 1q41q42 microdeletion syndrome. PMID- 27184007 TI - Mouse double minute 2 (MDM2) upregulates Snail expression and induces epithelial to-mesenchymal transition in breast cancer cells in vitro and in vivo. AB - The oncogene, mouse double minute 2 (MDM2), has been implicated in the pathogenesis of numerous cancers. In this study, we investigated the role of MDM2 in epithelial-to-mesenchymal transition (EMT) and the underlying mechanisms in breast cancer cells in vitro and in vivo. The results showed that up-regulation of MDM2 in MCF-7 cells altered the cell morphology to a mesenchymal phenotype. Knockdown of MDM2 in MDA-MB-231 cells altered the cell morphology to the epithelial phenotype. In addition, overexpression of MDM2 increased the expression of N-cadherin and Vimentin and decreased the expression of E-cadherin, at both the mRNA and protein levels, in vitro and in vivo. Conversely, down regulation of MDM2 decreased the expression of N-cadherin and Vimentin, and increased the expression of E-cadherin in vitro. Furthermore, MDM2 up-regulated both the mRNA and protein expression of Snail in vitro and in vivo. Knockdown of Snail almost abolished MDM2 induced EMT in vitro. Finally, we found that MDM2 expression correlated with EMT markers and Snail: Snail expression was inversely associated with E-cadherin in human breast cancer samples. Our findings demonstrated that MDM2 induces EMT by enhancing Snail expression in vitro and in vivo. Thus, MDM2 may be a potential target for therapy against human metastatic breast cancer. PMID- 27184009 TI - Reduced cell cohesiveness of outgrowths from eccrine sweat glands delays wound closure in elderly skin. AB - Human skin heals more slowly in aged vs. young adults, but the mechanism for this delay is unclear. In humans, eccrine sweat glands (ESGs) and hair follicles underlying wounds generate cohesive keratinocyte outgrowths that expand to form the new epidermis. Here, we compared the re-epithelialization of partial thickness wounds created on the forearm of healthy young (< 40 yo) and aged (> 70 yo) adults. Our results confirm that the outgrowth of cells from ESGs is a major feature of repair in young skin. Strikingly, in aged skin, although ESG density is unaltered, less than 50% of the ESGs generate epithelial outgrowths during repair (vs. 100% in young). Surprisingly, aging does not alter the wound-induced proliferation response in hair follicles or ESGs. Instead, there is an overall reduced cohesiveness of keratinocytes in aged skin. Reduced cell-cell cohesiveness was most obvious in ESG-derived outgrowths that, when present, were surrounded by unconnected cells in the scab overlaying aged wounds. Reduced cell cell contact persisted during the repair process, with increased intercellular spacing and reduced number of desmosomes. Together, reduced outgrowths of ESG (i) reduce the initial number of cells participating in epidermal repair, (ii) delay wound closure, and (iii) lead to a thinner repaired epidermis in aged vs. young skin. Failure to form cohesive ESG outgrowths may reflect impaired interactions of keratinocytes with the damaged ECM in aged skin. Our findings provide a framework to better understand the mediators of delayed re-epithelialization in aging and further support the importance of ESGs for the repair of human wounds. PMID- 27184010 TI - Highly Sensitive Built-In Strain Sensors for Polymer Composites: Fluorescence Turn-On Response through Mechanochemical Activation. AB - A new class of rationally designed mechanophores is developed for highly sensitive built-in strain sensors in polymer composites. These mechanophores are designed to regenerate the pi-conjugation pathway between the electron donor and electron acceptor by force-induced cleavage of the covalent bond to form a fluorescent dipolar dye. PMID- 27184011 TI - Biomimicking Nano-Micro Binary Polymer Brushes for Smart Cell Orientation and Adhesion Control. AB - A new biomimetic surface named nano-micro binary polymer brushes is fabricated by large-area bench-top dip-pen nanodisplacement lithography technique. It is composed of gelatin-modified poly(glycidyl methacrylate) nanolines which are spaced by microstripes of poly(N-isopropylacrylamide). Cells are not only adhered and oriented well on the re-used surface, but also detachable from the surface with well-preserved extracellular matrix and aligned morphology. PMID- 27184012 TI - Polytherapy and the risk of potentially inappropriate prescriptions (PIPs) among elderly and very elderly patients in three different settings (hospital, community, long-term care facilities) of the Friuli Venezia Giulia region, Italy: are the very elderly at higher risk of PIPs? AB - PURPOSE: The aim of this point-prevalence study was to assess the occurrence of polypharmacy and hyperpolypharmacy and the risk of potentially inappropriate prescriptions (PIPs) among elderly and very elderly patients in different health care settings of the Friuli-Venezia Giulia region in the North-East of Italy. METHODS: Prescription pattern of elderly (65-79 years) and very elderly (>79 years) patients in three different health-care settings [hospitals, general practitioners, and long-term care facilities (LTCFs)] was assessed in March 2014, and PIPs were assessed according to the Beers criteria. Other situations at potentially high risk were checked. RESULTS: A total of 1582 patients (hospital, n = 528; outpatients, n = 527; nursing homes, n = 527) were included. Very elderly were more represented in hospitals (60.4%) and LTCFs (77.1%) than among general practitioners (37.6%). Polypharmacy and hyperpolypharmacy rates ranged 57.7-73.7% and 9.7-15.6%, respectively. The most frequently prescribed drugs were the proton pump inhibitors, whereas the most common PIPs resulted the benzodiazepines. Multinomial regression analysis showed that female sex, age > 79 years, hyperpolypharmacy, and chronic kidney disease were associated with the risk of having >=2 PIPs. Two situations at high risk of PIPs not contemplated by the Beers criteria were recurrent in the study population and concerned the statins and metformin. CONCLUSIONS: Polypharmacy and hyperpolypharmacy among elderly and very elderly are strictly associated with the risk of multiple PIPs. The findings offer the opportunity to remark that improvement of the knowledge of safe drug use is generally needed in aging societies and may become of utmost relevance among health-care workers operating in LTCFs. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27184013 TI - Diagnostic Role of Captopril Challenge Test in Korean Subjects with High Aldosterone-to-Renin Ratios. AB - BACKGROUND: Diagnosis of primary aldosteronism (PA) begins with aldosterone-to renin ratio (ARR) measurement followed by confirmative tests. However, the ARR has high false positive rates which led to unnecessary confirmatory tests. Captopril challenge test (CCT) has been used as one of confirmatory tests, but the accuracy of it in the diagnosis of PA is still controversial. We aimed to examine the clinical efficacy of CCT as a post-screening test in PA. METHODS: In a prospective study, we enrolled subjects with suspected PA who had hypertension and ARR >20 (ng/dL)/(ng/mL/hr). Sixty-four patients who underwent both the saline infusion test and the CCT were included. RESULTS: The diagnostic performance of plasma aldosterone concentration (PAC) post-CCT was greater than that of ARR post CCT and ARR pre-CCT in PA (area under the curve=0.956, 0.797, and 0.748, respectively; P=0.001). A cut-off value of 13 ng/dL showed the highest diagnostic odds ratio considering PAC post-CCT at 60 and 90 minutes. A PAC post-CCT of 19 ng/dL had a specificity of 100%, which can be used as a cut-off value for the confirmative test. Determining the diagnostic performance of PAC post-CCT at 90 minutes was sufficient for PA diagnosis. Subjects with PAC post-CCT at 90 minutes <13 ng/dL are less likely to have PA, and those with PAC post-CCT at 90 minutes >=13 but <19 ng/dL should undergo secondary confirmatory tests. CONCLUSION: The CCT test may be a reliable post-screening test to avoid the hospitalization in the setting of falsely elevated ARR screening tests. PMID- 27184014 TI - Dissecting Tumor-Stromal Interactions in Breast Cancer Bone Metastasis. AB - Bone metastasis is a frequent occurrence in breast cancer, affecting more than 70% of late stage cancer patients with severe complications such as fracture, bone pain, and hypercalcemia. The pathogenesis of osteolytic bone metastasis depends on cross-communications between tumor cells and various stromal cells residing in the bone microenvironment. Several growth factor signaling pathways, secreted micro RNAs (miRNAs) and exosomes are functional mediators of tumor stromal interactions in bone metastasis. We developed a functional genomic approach to systemically identified molecular pathways utilized by breast cancer cells to engage the bone stroma in order to generate osteolytic bone metastasis. We showed that elevated expression of vascular cell adhesion molecule 1 (VCAM1) in disseminated breast tumor cells mediates the recruitment of pre-osteoclasts and promotes their differentiation to mature osteoclasts during the bone metastasis formation. Transforming growth factor beta (TGF-beta) is released from bone matrix upon bone destruction, and signals to breast cancer to further enhance their malignancy in developing bone metastasis. We furthered identified Jagged1 as a TGF-beta target genes in tumor cells that engaged bone stromal cells through the activation of Notch signaling to provide a positive feedback to promote tumor growth and to activate osteoclast differentiation. Substantially change in miRNA expression was observed in osteoclasts during their differentiation and maturation, which can be exploited as circulating biomarkers of emerging bone metastasis and therapeutic targets for the treatment of bone metastasis. Further research in this direction may lead to improved diagnosis and treatment strategies for bone metastasis. PMID- 27184016 TI - 18F-FDG PET/CT-Guided Clinical Management of the Rare Aggressive "Columnar-Cell" Variant of Papillary Thyroid Cancer. PMID- 27184015 TI - Clinical Relevance of Environmental Factors in the Pathogenesis of Autoimmune Thyroid Disease. AB - Genetic factors contribute for about 70% to 80% and environmental factors for about 20% to 30% to the pathogenesis of autoimmune thyroid disease (AITD). Relatives of AITD patients carry a risk to contract AITD themselves. The 5-year risk can be quantified by the so-called Thyroid Events Amsterdam-score, based on serum thyroid-stimulating hormone, thyroid peroxidase (TPO)-antibodies and family history. Subjects at risk may ask what they can do to prevent development of AITD. This review summarizes what is known about modulation of exposure to environmental factors in terms of AITD prevention. To stop smoking decreases the risk on Graves disease but increases the risk on Hashimoto disease. Moderate alcohol intake provides some protection against both Graves and Hashimoto disease. Low selenium intake is associated with a higher prevalence of thyroid autoimmunity, but evidence that selenium supplementation may lower TPO antibodies and prevent subclinical hypothyroidism remains inconclusive. Low serum vitamin D levels are associated with a higher prevalence of TPO antibodies, but intervention studies with extra vitamin D have not been done yet. Stress may provoke Graves hyperthyroidism but not Hashimoto thyroiditis. Estrogen use have been linked to a lower prevalence of Graves disease. The postpartum period is associated with an increased risk of AITD. Taking together, preventive interventions to diminish the risk of AITD are few, not always feasible, and probably of limited efficacy. PMID- 27184017 TI - Triiodothyronine Levels Are Independently Associated with Metabolic Syndrome in Euthyroid Middle-Aged Subjects. AB - BACKGROUND: Recent studies have shown an association between thyroid hormone levels and metabolic syndrome (MetS) among euthyroid individuals; however, there have been some inconsistencies between studies. Here, we evaluated the relationship between thyroid hormone levels and MetS in euthyroid middle-aged subjects in a large cohort. METHODS: A retrospective analysis of 13,496 euthyroid middle-aged subjects who participated in comprehensive health examinations was performed. Subjects were grouped according to thyroid stimulating hormone, total triiodothyronine (T3), total thyroxine (T4), and T3-to-T4 ratio quartile categories. We estimated the odds ratios (ORs) for MetS according to thyroid hormone quartiles using logistic regression models, adjusted for potential confounders. RESULTS: Of the study patients, 12% (n=1,664) had MetS. A higher T3 level and T3-to-T4 ratio were associated with unfavourable metabolic profiles, such as higher body mass index, systolic and diastolic blood pressure, triglycerides, fasting glucose and glycated hemoglobin, and lower high density lipoprotein cholesterol levels. The proportion of participants with MetS increased across the T3 quartile categories (P for trend <0.001) and the T3-to-T4 ratio quartile categories (P for trend <0.001). The multi-variate-adjusted OR (95% confidence interval) for MetS in the highest T3 quartile group was 1.249 (1.020 to 1.529) compared to the lowest T3 quartile group, and that in the highest T3-to-T4 ratio quartile group was 1.458 (1.141 to 1.863) compared to the lowest T3-to-T4 ratio quartile group, even after adjustment for potential confounders. CONCLUSION: Serum T3 levels and T3-to-T4 ratio are independently associated with MetS in euthyroid middle-aged subjects. Longitudinal studies are needed to define this association and its potential health implications. PMID- 27184018 TI - Evaluation of the role of the GPIb-IX-V receptor complex in development of the platelet storage lesion. AB - BACKGROUND AND OBJECTIVES: In mice, loss of sialic acid resulting in shedding of glycoprotein (GP) Ibalpha and GPV has been linked to platelet survival. The aim of this study was to determine whether loss of sialic acid and the GPIb-IX-V complex contributes to development of the platelet storage lesion (PSL) in human platelet concentrates (PCs). MATERIALS AND METHODS: PCs (stored in plasma (with or without Mirasol treatment); PAS-C or PAS-E) were stored at room temperature. Flow cytometry was used to monitor membrane expression of the GPIb-IX-V complex, CD62P, surface glycans and PS exposure. The functionality of stored platelets was determined employing aggregometry and ristocetin-induced VWF binding. RESULTS: Storage time of PCs in blood banks is limited to 7 days. During this time period, a minor but gradually increasing subpopulation of GPIbalpha-negative platelets was observed. Also, ristocetin-induced VWF binding was impaired in a small population of platelets. Mean surface expression of GPIbalpha and GPV remained stable until day 9, whereas CD62P expression increased; also a rapid decrease in ADP-induced aggregation was observed for PAS-C, PAS-E and Mirasol-treated PCs. Upon prolonged storage (>9 days), a slow decline in surface expression of GPIbalpha and GPV was observed; no major changes were observed in surface sialylation with the exception of Mirasol-treated platelets. CONCLUSION: In a small population of stored platelets, changes in GPIbalpha occur from day 2 onwards. Loss of sialic acid and subsequent shedding of GPIbalpha and GPV is not an early event during the development of the PSL. PMID- 27184019 TI - Multiparametric magnetic resonance imaging: Current role in prostate cancer management. AB - Digital rectal examination, serum prostate-specific antigen screening and transrectal ultrasound-guided biopsy are conventionally used as screening, diagnostic and surveillance tools for prostate cancer. However, they have limited sensitivity and specificity. In recent years, the role of multiparametric magnetic resonance imaging has steadily grown, and is now part of the standard clinical management in many institutions. In multiparametric magnetic resonance imaging, the morphological assessment of T2-weighted imaging is correlated with diffusion-weighted imaging, dynamic contrast-enhanced imaging perfusion and/or magnetic resonance spectroscopic imaging. Multiparametric magnetic resonance imaging is currently regarded as the most sensitive and specific imaging technique for the evaluation of prostate cancer, including detection, staging, localization and aggressiveness evaluation. This article presents an overview of multiparametric magnetic resonance imaging, and discusses the current role of multiparametric magnetic resonance imaging in the different fields of prostate cancer management. PMID- 27184020 TI - Prenatal ultrasound and childhood autism: long-term follow-up after a randomized controlled trial of first- vs second-trimester ultrasound. AB - OBJECTIVE: To analyze whether the frequency of autism spectrum disorder (ASD) in a cohort of Swedish children differs between those exposed to ultrasound in the 12(th) week and those exposed to ultrasound in the 18(th) week of gestation. METHODS: The study cohort consisted of approximately 30 000 children born between 1999 and 2003 to mothers who had been randomized to a prenatal ultrasound examination at either 12 or 18 weeks' gestation as part of the framework for a study on nuchal translucency screening. The outcome measure in the present study was the rate of ASD diagnoses among the children. Information on ASD diagnoses was based on data from the Swedish social insurance agency concerning childcare allowance granted for ASD. RESULTS: Between 1999 and 2003, a total of 14 726 children were born to women who underwent a 12-week ultrasound examination and 14 596 to women who underwent an 18-week ultrasound examination. Of these, 181 (1.2%) and 176 (1.2%) children, respectively, had been diagnosed with ASD. There was no difference in ASD frequency between the early and late ultrasound groups. CONCLUSIONS: Women subjected to at least one prenatal ultrasound examination at either 12 or 18 weeks' gestation had children with similar rates of ASD. However, this result reflects routine care 10-15 years ago in Sweden. Today, higher intensity ultrasound scans are performed more frequently, at earlier stages during pregnancy and for non-medical purposes, implying longer exposure time for the fetus. This change in the use of ultrasound necessitates further follow-up study of the possible effects that high exposure to ultrasound during the gestational period has on the developing brain. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 27184021 TI - Interaction with slow waves during sleep improves discrimination of physiologic and pathologic high-frequency oscillations (80-500 Hz). AB - OBJECTIVE: To characterize the interaction between physiologic and pathologic high-frequency oscillations (HFOs) and slow waves during sleep, and to evaluate the practical significance of these interactions by automatically classifying channels as recording from normal or epileptic brain regions. METHODS: We automatically detected HFOs in intracerebral electroencephalography (EEG) recordings of 45 patients. We characterized the interaction between the HFOs and the amplitude and phase of automatically detected slow waves during sleep. We computed features associated with HFOs, and compared classic features such as rate, amplitude, duration, and frequency to novel features related to the interaction between HFOs and slow waves. To quantify the practical significance of the difference in these features we classified the channels as recording from normal/epileptic regions using logistic regression. We assessed the results in different brain regions to study differences in the HFO characteristics at the lobar level. RESULTS: We found a clear difference in the coupling between the phase of slow waves during sleep and the occurrence of HFOs. In channels recording physiologic activity, the HFOs tend to occur after the peak of the deactivated state of the slow wave, and in channels with epileptic activity, the HFOs occur more often before this peak. This holds for HFOs in the ripple (80-250 Hz) and fast ripple (250-500 Hz) bands, and different regions of the brain. When using this interaction to automatically classify channels as recording from normal/epileptic brain regions, the performance is better than when using other HFO characteristics. We confirmed differences in the HFO characteristics in mesiotemporal structures and in the occipital lobe. SIGNIFICANCE: We found the association between slow waves and HFOs to be different in normal and epileptic brain regions, emphasizing their different origin. This is also of practical significance, since it improves the separation between channels recording from normal and epileptic brain regions. PMID- 27184022 TI - Unexpected cholesterol gallstones. PMID- 27184023 TI - Is the Lack of Specific Lesbian, Gay, Bisexual, Transgender and Queer/Questioning (LGBTQ) Health Care Education in Medical School a Cause for Concern? Evidence From a Survey of Knowledge and Practice Among UK Medical Students. AB - Lesbian, gay, bisexual, transgender and queer/questioning (LGBTQ) people frequently report negative health care encounters. Medical professionals may inadequately manage LGBTQ persons' health if they have not received training in this area. An anonymous survey measuring efficacy in health situations among LGBTQ persons was answered by 166 medical students across all years of a UK university. Results show that 84.9% of participants reported a lack of LGBTQ health care education, with deficits in confidence clarifying unfamiliar sexual and gender terms, deciding the ward in which to nurse transgender patients, finding support resources, and discussing domestic abuse with LGBTQ patients. Most participants reported that they would not clarify gender pronouns or ask about gender or sexual identity in mental health or reproductive health settings. Participants reported infrequently observing doctors making similar inquiries. Participants held positive attitudes toward LGBTQ patients, with attitude scores positively correlating with LGBTQ terminology knowledge scores (rs = 0.5052, p < .01). Addressing gender identity and sexuality issues within medical curricula may remove barriers to accessing health care and improve encounters for LGBTQ patients. PMID- 27184024 TI - First record of the Asian bush mosquito, Aedes japonicus japonicus, in Italy: invasion from an established Austrian population. AB - BACKGROUND: In 2011 we identified the Asian bush mosquito, Aedes japonicus japonicus (Theobald, 1901) (Diptera: Culicidae) for the first time in northern Slovenia and in the bordering Austrian federal state of Styria. Between May and July 2012 the distribution area of Ae. j. japonicus was already found to be extended westwards into Carinthia and eastwards towards Burgenland and bordering Hungary. In August 2012 the species was first detected in a western province of Hungary. In subsequent years, follow-up field studies demonstrated an active spread westwards throughout Carinthia, reaching the border to northern Italy. FINDINGS: In July 2015 several aquatic-stage specimens of the species were discovered at three different sites in the Friuli Venezia Giulia region, north eastern Italy. In September 2015, co-occurrence of Ae. j. japonicus and Aedes albopictus (Skuse, 1895) was observed in the same sample in that region. CONCLUSIONS: Ae. j. japonicus actively extended its geographic range from an established population in Carinthia (Austria) southwards to northern Italy by crossing Alpine ranges. Since Ae. albopictus and Aedes koreicus (Edwards, 1917) are already well established in northern Italy, it will be pivotal to monitor the consequences of a third invasive mosquito species trying to populate the same geographic region. PMID- 27184025 TI - What are the risk factors for HIV in men who have sex with men in Ho Chi Minh City, Vietnam?- A cross-sectional study. AB - BACKGROUND: The number of people living with HIV (PLWH) in Vietnam was estimated to rise from 156,802 in 2009 to 256,000 in 2014. Although the number of new HIV reported cases has decreased by roughly 14,000 cases per year from 2010 to 2013 a concerning increase in HIV prevalence has been identified among men who have sex with men (MSM) from 1.7 % in 2005 to 2.4 % in 2013. There are signs of increased HIV (+) prevalence among MSM in a number of cities/provinces, especially in the two largest cities, Ho Chi Minh City (HCMC) and Hanoi. HCMC is the country's major "hot spot" for HIV/AIDS, with over a third of the total national AIDS patients. This paper is based on a secondary analysis of Integrated Biological and Behavioural Surveillance (IBBS) data collected in Vietnam in 2009 to examine the research question "Do behavioural risk factors contribute to HIV infection among the MSM population in HCMC?". METHODS: A cross-sectional design was employed to sample males aged over 15 from communities in HCMC, who reported having any types of sex with another man at least once during the last 12 months. Participants (399) were recruited using the respondent driven sampling (RDS) method and provided both biological data (specimens) and behavioural data collected through a questionnaire survey. RESULTS: The study found high HIV prevalence (14.8 %) among the MSM sample from HCMC. Multivariate analysis found age and level of formal education completed, to be significantly associated with HIV infection. MSM aged over 25 were more likely to be HIV (+) than the younger group (OR = 7.82, 95 %CI = 3.37-18.16, p < 0.001); as were participants who had low educational (OR = 2.74, p < 0.05) and medium educational levels (OR = 2.68, p < 0.05). In addition, those participants who had anal sex with male partners (OR = 2.7, p < 0.05) and whose sexual partners injected drugs (OR = 2.24, p < 0.05) and who felt at risk of HIV infection (OR = 2.42, p < 0.01) had a higher risk of HIV infection. CONCLUSIONS: The high proportion of HIV (+) MSM in our sample from HCMC indicates that we need a better understanding of MSM behaviour patterns, risk practices and social networks as well as improved HIV prevention and control measures. More targeted and relevant HIV prevention programs for older and less educated MSM are urgently needed to address the key risk factors we have identified. MSM engaging in drug-related risk behaviours require multi-strategy HIV interventions relating to both sex and drug behaviour among MSM and their partners who engage in drug use. Further work is needed to identify locations and strategies where these high-risk individuals can be accessed as well as to reduce barriers related to social discrimination and stigma. Targeting high risk individuals and groups should supplement existing efforts aimed at the MSM population in HCMC. PMID- 27184026 TI - Effect of pregnancy intention, postnatal depressive symptoms and social support on early childhood stunting: findings from India. AB - BACKGROUND: According to United Nation Children's Fund, it has been estimated that worldwide about 165 million children were stunted in 2012 and India alone accounts for 38 % of global burden of stunting. This study aims to examine the effect of pregnancy intention and maternal postnatal depressive symptoms on early childhood stunting in India. We hypothesized that effect of pregnancy intention and postnatal depressive symptoms were mediated by social support. METHODS: We used data from the first wave of Young Lives Study India. Multivariate logistic regression models (using generalized estimation equation) were used to examine the effect of pregnancy intention and postnatal depressive symptoms on early childhood stunting among children aged 5-21 months. The analysis included 1833 children (out of 2011 sample children) that had complete information on pregnancy intention, maternal depression and other variables. RESULTS: Bivariate results indicate that a higher percent of children born after unintended pregnancy (40 %) were stunted than children of intended pregnancy (26 %). Likewise, the proportion of stunted children was also higher among women with high postnatal depressive symptoms (35 %) than the low level of depression (24 %). Results of multivariate logistic regression model indicate that children born after unintended pregnancy were significantly more likely to be stunted than children born after intended pregnancy (AOR: 1.76, CI: 1.25, 2.48). Similarly, early childhood stunting was also associated with maternal postnatal depressive symptoms (AOR: 1.53, CI: 1.21, 1.92). Moreover, the effect of pregnancy intention and postnatal depressive symptoms on early childhood stunting were not mediated by social support. CONCLUSIONS: The findings of this study provide conclusive evidence regarding consequences of pregnancy intention and postnatal depressive symptoms on early childhood stunting in India. Therefore, there is a need to identify the women with unintended pregnancy and incorporate the promotion of mental health into their national reproductive and child health programme. PMID- 27184027 TI - Occupational and environmental risk factors for chronic rhinosinusitis in China: a multicentre cross-sectional study. AB - BACKGROUND: Chronic rhinosinusitis (CRS) is defined as a condition of inflammation in the paranasal sinus mucosa persisting for more than 12 weeks. We previously reported that the prevalence of CRS was about 8 % in China. Here, we aim to investigate the occupational and environmental risk factors associated with CRS. METHODS: Data were collected from seven Chinese cities: Urumqi, Changchun, Beijing, Wuhan, Chengdu, Huaian and Guangzhou. CRS was diagnosed according to the European Position Paper on Rhinosinusitis and Nasal Polyps (EP(3)OS) document. Participants were asked to complete a standardized questionnaire, which was developed by the Global Allergy and Asthma European Network (GA(2)LEN) project and covered sociodemographic characteristics, CRS related symptoms and occupational and environmental exposures. We evaluated the association between CRS and various occupational and environmental factors using odds ratios (ORs) and 95 % confidence intervals (95 % CIs). RESULTS: The total study population consisted of 10,633 subjects, 850 (7.99 %) of whom were defined as having CRS according to the EP(3)OS criteria. We found that there were significant associations between occupational and environmental factors and CRS. Specifically, having a clearance-related job, occupational exposure to dust, occupational exposure to poisonous gas, a pet at home or carpet at home or at the workplace were risk factors for CRS. Additionally, the method used to keep warm in winter, the duration of time spent using air conditioning in summer and the frequency of exposure to mouldy or damp environments were significantly different in subjects with and without CRS. CONCLUSIONS: Our data showed that some occupational and environmental exposures are strongly associated with CRS, which aids in understanding the epidemiology of CRS. PMID- 27184030 TI - Dissecting the Mechanisms of Thrombogenesis and Atherosclerosis for Neurodegenerative Disorders. PMID- 27184028 TI - Induced pluripotent stem cells in Alzheimer's disease: applications for disease modeling and cell-replacement therapy. AB - Alzheimer's disease (AD) is the most common cause of dementia in those over the age of 65. While a numerous of disease-causing genes and risk factors have been identified, the exact etiological mechanisms of AD are not yet completely understood, due to the inability to test theoretical hypotheses on non-postmortem and patient-specific research systems. The use of recently developed and optimized induced pluripotent stem cells (iPSCs) technology may provide a promising platform to create reliable models, not only for better understanding the etiopathological process of AD, but also for efficient anti-AD drugs screening. More importantly, human-sourced iPSCs may also provide a beneficial tool for cell-replacement therapy against AD. Although considerable progress has been achieved, a number of key challenges still require to be addressed in iPSCs research, including the identification of robust disease phenotypes in AD modeling and the clinical availabilities of iPSCs-based cell-replacement therapy in human. In this review, we highlight recent progresses of iPSCs research and discuss the translational challenges of AD patients-derived iPSCs in disease modeling and cell-replacement therapy. PMID- 27184029 TI - Small RNA sequencing and degradome analysis of developing fibers of short fiber mutants Ligon-lintles-1 (Li 1 ) and -2 (Li 2 ) revealed a role for miRNAs and their targets in cotton fiber elongation. AB - BACKGROUND: The length of cotton fiber is an important agronomic trait that directly affects the quality of yarn and fabric. Understanding the molecular basis of fiber elongation would provide a means for improvement of fiber length. Ligon-lintless-1 (Li 1 ) and -2 (Li 2 ) are monogenic and dominant mutations that result in an extreme reduction in the length of lint fiber on mature seeds. In a near-isogenic state with wild type cotton these two short fiber mutants provide an effective model system to study the mechanisms of fiber elongation. Plant miRNAs regulate many aspects of growth and development. However, the mechanism underlying the miRNA-mediated regulation of fiber development is largely unknown. RESULTS: Small RNA libraries constructed from developing fiber cells of the short fiber mutants Li 1 and Li 2 and their near-isogenic wild type lines were sequenced. We identified 24 conservative and 147 novel miRNA families with targets that were detected through degradome sequencing. The distribution of the target genes into functional categories revealed the largest set of genes were transcription factors. Expression profiles of 20 miRNAs were examined across a fiber developmental time course in wild type and short fiber mutations. We conducted correlation analysis between miRNA transcript abundance and the length of fiber for 11 diverse Upland cotton lines. The expression patterns of 4 miRNAs revealed significant negative correlation with fiber lengths of 11 cotton lines. CONCLUSIONS: Our results suggested that the mutations have changed the regulation of miRNAs expression during fiber development. Further investigations of differentially expressed miRNAs in the Li 1 and Li 2 mutants will contribute to better understanding of the regulatory mechanisms of cotton fiber development. Four miRNAs negatively correlated with fiber length are good candidates for further investigations of miRNA regulation of important genotype dependent fiber traits. Thus, our results will contribute to further studies on the role of miRNAs in cotton fiber development and will provide a tool for fiber improvement through molecular breeding. PMID- 27184031 TI - Dabigatran Etexilate Reduces Thrombin-Induced Inflammation and Thrombus Formation in Experimental Ischemic Stroke. AB - Dabigatran etexilate (DE), a direct-acting, oral inhibitor of thrombin, significantly reduces the risk of stroke compared with traditional anticoagulants, without increasing the risk of major bleeding. However, studies on the fate of cerebral tissue after ischemic stroke in patients receiving DE are sparse and the role of dabigatran-mediated reduction of thrombin in this context has not yet been investigated. Here, we investigated whether pretreatment with DE reduces thrombin-mediated pro-inflammatory mechanisms and leakage of the blood brain barrier (BBB) following ischemic stroke in rats. Male Wistar rats received DE (15 mg/kg) or a vehicle solution 1 hour before transient middle cerebral artery occlusion (tMCAO) for 90 minutes. Infarct volume, neurologic outcome and intracranial hemorrhage (ICH) were determined after tMCAO. Thrombin generation was indirectly assessed by measuring thrombin/antithrombin III complex. Microvascular patency was evaluated histologically. Cytokine expression and immunoreactivity of cluster of differentiation (CD) 68 were examined to characterize inflammatory processes after pretreatment with DE. BBB integrity was examined by quantifying brain edema. Rats given DE revealed a significant reduction in infarct size without an increase in ICH and significant recovery of neurologic deficits compared to controls. Administration of DE decreased thrombin generation and thrombus formation, dampened the CD68-immunoreactivity and attenuated pro-inflammatory cytokine expression in the cerebral parenchyma ipsilateral to the ischemic lesion. BBB permeability was unaltered following treatment with DE. In summary, prophylactic anticoagulation with DE improves stroke outcome by reducing thrombin-induced inflammation and thrombus formation without increasing the rate of ICH. PMID- 27184032 TI - Mean Platelet Volume During Ischemic Stroke is a Potential Pro-inflammatory Biomarker in the Acute Phase and During Neurorehabilitation Not Directly Linked to Clinical Outcome. AB - The prognostic role of increased mean platelet volume (MPV), as an indicator of platelet activation and large, more reactive platelets, in clinical and functional outcome of ischemic stroke is still conflicting. Studies are not currently available on the association between MPV and stroke recovery after neurorehabilitation. The relationship between MPV and clinical and functional outcome measures was assessed in twenty-four patients in the acute phase of first ever ischemic stroke, and before and after 8-week intensive multifunctional neurorehabilitation. Neurorehabilitation was associated with improved scores of the National Institutes of Health Stroke Scale (NIHSS), the modified Rankin Scale (mRS), and the modified PULSES profile (mPULSES). When compared with apparently healthy subjects, higher MPV values were observed in stroke patients 24 hours after stroke and before neurorehabilitative treatment started not later than 14 days after stroke. Decreased MPV values were found after neurorehabilitation, even if the absolute values were still higher than those detected in control subjects. No correlation was observed between MPV values and scores of the NIHSS and mRS scales evaluated in stroke acute phase. No correlation was also observed before and after neurorehabilitative treatment between MPV and NIHSS, mRS and mPULSES scores. Our data provide evidence of the effectiveness of neurorehabilitation on modulating MPV values and support the hypothesis that high MPV could represent an expression of proinflammatory condition of the stroke patients, realistically pre-existent to acute ischemic event, than a marker of neurologic deficit and disability or of stroke recovery including motor performance and functional independence. PMID- 27184033 TI - Metachronous testicular seminoma after radiotherapy and chemotherapy: a case report. AB - BACKGROUND: Bilateral testicular neoplasia is rare, with an incidence ranging from 1 to 5%. Long-term survival has improved in recent years due to advanced diagnostic approaches and new therapeutic methods that are highly effective against germ cell tumors. CASE PRESENTATION: We present the case of a patient with a primary seminomatous testicular tumor, who developed a contralateral metastasis and a subsequent metachronous tumor following chemotherapy and consolidation radiotherapy treatment. CONCLUSIONS: Strict follow-up, including physical examination and ultrasound examination of the contralateral testis, enabled early diagnosis of the second tumor, giving the patient a high likelihood of a definitive cure. PMID- 27184034 TI - Changing the Cancer Diagnosis: The Case of Follicular Variant of Papillary Thyroid Cancer-Primum Non Nocere and NIFTP. PMID- 27184035 TI - The role of mean platelet volume and platelet distribution width in the prediction of placental abruption. AB - We determined the role of mean platelet volume (MPV) and platelet distribution width (PDW) in the prediction of placental abruption (PA) prior to caesarean section. Data obtained between January 2011 and July 2014 from patients (n = 33) with PA and healthy control subjects (n = 67) matched for age- and gestation stage were analysed. Pre-operative and post-operative MPV and PDW were significantly different between the PA and control groups when cut-off values for MPV were set at 9.23; sensitivity at 87.8% and specificity at 46.2%; positive predictive value (PPV) at 48.3%; and negative predictive value (NPV) at 90.0%. When the cut-off value for PDW was set at 18.5, the sensitivity was 100% and specificity 71.6%, PPV 40.7% and NPV 59.3% for the prediction of PA. MPV and PDW levels were significantly higher in cases of PA. These results suggest that clinical evaluation of MPV and PDW displays reasonable sensitivity and specificity as a marker of PA, prompting the need for more research in this area of clinical study. PMID- 27184036 TI - Treatment patterns and comparative effectiveness in elderly acute myeloid leukemia patients (age 70 years or older): the Lyon-university hospital experience. AB - The treatment of very elderly patients (>=70 years) with acute myeloid leukemia remains controversial. We present here 302 patients seen over a 14-year period in order to understand the real-world treatment patterns and outcomes in this patient population. Less than 25% of patients achieved a complete remission. The median overall survival was 12.4, 11.5 and 2.6 months, with a 3-year rates of 27%, 17% and 6%, for non-acute promyelocytic leukemia patients receiving intensive chemotherapy, lower-intensity therapy or best supportive care (BSC), respectively. In all ages, results were not significantly different among patients receiving low-intensity therapy and intensive chemotherapy, but significantly worse in those treated with BSC only. Similarly, intensive chemotherapy and low-intensity therapy gave better survival rates than BSC in patients with favorable- or intermediate-risk cytogenetics and in those with unfavorable cytogenetics (p < 0.0001 and p = 0.04, respectively). PMID- 27184038 TI - Erratum. PMID- 27184037 TI - Freezing oocytes or embryos after controlled ovarian hyperstimulation in cancer patients: the state of the art. AB - Quality of life of young cancer survivors has become a major issue. However, anticancer therapies can have a detrimental impact on fertility. It is now well established that all patients should receive information about the fertility risks associated with their cancer treatment and the fertility preservation options available. Currently, oocyte or embryo banking after controlled ovarian hyperstimulation represents the most effective method for preserving female fertility. Over the past years innovative protocols of ovarian stimulation have been developed to enable cancer patients to undergo oocyte or embryo cryopreservation irrespective of the phase of the cycle or without exogenous follicle-stimulating hormone-related increase in serum estradiol levels. The present article reviews the different protocols of ovarian hyperstimulation for cancer patients, candidates for fertility preservation. PMID- 27184039 TI - Moderate, Regular Alcohol Consumption is Associated with Higher Cognitive Function in Older Community-Dwelling Adults. AB - BACKGROUND: Evidence suggests that moderate alcohol consumption may protect against cognitive decline and dementia. However, uncertainty remains over the patterns of drinking that are most beneficial. OBJECTIVE: To examine associations between amount and frequency of alcohol consumption with multiple domains of cognitive function in a well-characterized cohort of older community-dwelling adults in southern California. DESIGN: Observational, cross-sectional cohort study. SETTING: A research visit between 1988-1992 in Rancho Bernardo, California. PARTICIPANTS: 1624 participants of the Rancho Bernardo Study (mean age +/- SD = 73.2 +/- 9.3 years). Measurements: Participants completed a neuropsychological test battery, self-administered questionnaires on alcohol consumption and lifestyle, and a clinical health evaluation. We classified participants according to average amount of alcohol intake into never, former, moderate, heavy and excessive drinkers, and according to frequency of alcohol intake, into non-drinkers, rare, infrequent, frequent and daily drinkers. We examined the association between alcohol intake and cognitive function, controlling for age, sex, education, exercise, smoking, waist-hip ratio, hypertension and self-assessed health. RESULTS: Amount and frequency of alcohol intake were significantly associated with cognitive function, even after controlling for potentially related health and lifestyle variables. Global and executive function showed positive linear associations with amount and frequency of alcohol intake, whereas visual memory showed an inverted U-shaped association with alcohol intake, with better performance for moderate and infrequent drinkers than for non-drinkers, excessive drinkers or daily drinkers. CONCLUSIONS: In several cognitive domains, moderate, regular alcohol intake was associated with better cognitive function relative to not drinking or drinking less frequently. This suggests that beneficial cognitive effects of alcohol intake may be achieved with low levels of drinking that are unlikely to be associated with adverse effects in an aging population. PMID- 27184042 TI - Effects of fixed time AI and AI at detected estrus on conception rate in smallholder zebu and crossbred heifers and cows subjected to double PGF2alpha administration. AB - The study was conducted to evaluate estrus response, time to the onset of estrus, and conception rate at fixed time AI and AI at detected estrus in local and crossbred heifers and cows subjected to double administration of PGF2alpha. One hundred twenty local (heifers, n = 27; cows, n = 33) and crossbreds (heifers, n = 21; cows, n = 39) were used for the study. About 63 and 85.7 % of the local and crossbred heifers, respectively, exhibited estrus. Similarly, all crossbred cows and 90.9 % of local cows showed estrus. Most heifers came to estrus between 48 and 72 h while cows exhibited behavioral signs of estrus between 72 and 96 h. AI at detected estrus resulted in higher conception rate than fixed time AI. Pregnancy per artificial insemination was higher in AI at detected estrus than fixed time AI. Accurate estrus detection followed by insemination are crucial factors in maximizing pregnancy, and this study has demonstrated that conception rate in smallholder heifers and cows should be inseminated following estrus detection to maximize the conception rate of the animals. PMID- 27184041 TI - Stem Cells in the Intestine: Possible Roles in Pathogenesis of Irritable Bowel Syndrome. AB - Irritable bowel syndrome is one of the most common functional gastrointestinal (GI) disorders that significantly impair quality of life in patients. Current available treatments are still not effective and the pathophysiology of this condition remains unclearly defined. Recently, research on intestinal stem cells has greatly advanced our understanding of various GI disorders. Alterations in conserved stem cell regulatory pathways such as Notch, Wnt, and bone morphogenic protein/TGF- beta have been well documented in diseases such as inflammatory bowel diseases and cancer. Interaction between intestinal stem cells and various signals from their environment is important for the control of stem cell self renewal, regulation of number and function of specific intestinal cell types, and maintenance of the mucosal barrier. Besides their roles in stem cell regulation, these signals are also known to have potent effects on immune cells, enteric nervous system and secretory cells in the gut, and may be responsible for various aspects of pathogenesis of functional GI disorders, including visceral hypersensitivity, altered gut motility and low grade gut inflammation. In this article, we briefly summarize the components of these signaling pathways, how they can be modified by extrinsic factors and novel treatments, and provide evidenced support of their roles in the inflammation processes. Furthermore, we propose how changes in these signals may contribute to the symptom development and pathogenesis of irritable bowel syndrome. PMID- 27184043 TI - Gastric Cancer: How Can We Reduce the Incidence of this Disease? AB - Gastric cancer remains a prevalent disease worldwide with a poor prognosis. Helicobacter pylori plays a major role in gastric carcinogenesis. H. pylori colonization leads to chronic gastritis, which predisposes to atrophic gastritis, intestinal metaplasia, dysplasia, and eventually gastric cancer. Screening, treatment, and prevention of H. pylori colonization can reduce the incidence of gastric cancer. Other interventions that may yield a similar effect, although of smaller magnitude, include promotion of a healthy lifestyle including dietary measures, non-smoking, low alcohol intake, and sufficient physical activity. This chapter reviews interventions that can lead to a decline in gastric cancer incidence in high and low incidence countries. PMID- 27184045 TI - Defining and evaluating a novel outcome measure representing end-stage knee osteoarthritis: data from the Osteoarthritis Initiative. AB - We described a definition of end-stage knee osteoarthritis (esKOA) and evaluated its association with health outcomes and osteoarthritis risk factors. We included Osteoarthritis Initiative participants with or at risk for knee osteoarthritis who had complete baseline data. We defined esKOA by adapting a validated appropriateness algorithm for total knee replacement based on data from baseline and the first four follow-up visits. We performed person-based analyses, including both knees from all participants. Participants met the definition of esKOA at the visit at which >=1 knee reached the esKOA criteria. We assessed differences in individual characteristics between groups at baseline and over time and tested if incident esKOA (outcome) was associated with osteoarthritis risk factors (e.g., age, maximum adult weight, and quadriceps strength). The cohort consisted of 3916 participants with mean age of 61 (SD = 9) years and mean body mass index of 28.4 (4.7) kg/m(2); 59 % were female and 9.7 % developed incident esKOA. Those with incident esKOA had poorer health outcomes at baseline and greater declines in health outcomes, with the exception of SF-12 mental health score. Five out of nine tested risk factors were associated with incident esKOA in unadjusted analyses, with older age (>=65 years; odds ratio = 1.44, 95 % confidence interval = 1.19 to 1.83) and quadriceps weakness (odds ratio = 0.78, 95 % confidence interval = 0.71 to 0.86) remaining significant in adjusted models. Older age and quadriceps weakness predicted esKOA. esKOA is also characterized by poor health-related outcomes. This definition of esKOA could be a new clinically relevant outcome measure for osteoarthritis research. PMID- 27184044 TI - Practical Approaches to "Top-Down" Therapies for Crohn's Disease. AB - Crohn's disease (CD) is a chronic, progressive, and disabling disease that leads in most cases to the development of bowel damage presenting as a fistula, abscess, or stricture. For years, therapy for Crohn's disease has been based on a "step-up" approach, in which anti-TNF agents are administered after the failure of steroids and immunosuppressants. However, recent studies have suggested that early introduction of anti-TNF agents combined with immunosuppressants can modify the natural history of the disease. Patients who could benefit more of this "top down" strategy would be those at elevated risk of a complicated or severe inflammatory bowel disease or with factors that can predict an aggressive disease course. Therefore, the management of a patient with CD should be personalized, taking into account the patient's specific characteristics and comorbidities, disease activity, site and behavior of the disease, and predictable factors of poor prognosis. A balance between medication and potential adverse effects should be achieved, trying to avoid under or overtreatment, always discussing the different therapeutic options with the patient. The natural history of ulcerative colitis differs from CD and, to date, there is not much scientific evidence on the use of early combined immunosuppression. PMID- 27184046 TI - A randomized, controlled trial of efficacy and safety of Anbainuo, a bio-similar etanercept, for moderate to severe rheumatoid arthritis inadequately responding to methotrexate. AB - The objective of the study was to evaluate the efficacy and safety of etanercept (Anbainuo) treatment in Chinese moderate to severe rheumatoid arthritis (RA) with inadequate response to methotrexate (MTX-IR); 600 patients (360 in phase III-1 and 240 in phase III-2) poorly responding to MTX were enrolled in the study and randomized at a ratio of 2:1 into an Anbainuo treatment or control group. The study was designed as a 12-week double-blind, placebo-controlled period followed by a 12-week open-label study. The primary endpoint was the ACR20 response rate at week 12. Secondary endpoints included the ACR50, ACR70, ACR-N, and safety. At week 12, ACR20 response was observed in 60.9 % of the Anbainuo group significantly higher than that of the control group (20.6 %). At week 24, the ACR20 response in the Anbainuo group increased to 70.2 %; there was no significant difference compared with that of the control group (61.8 %, P > 0.05). At week 12, the ACR50 and ACR70 responses of the Anbainuo group increased to 25.6 and 6.8 %, compared to 4 and 1 % in the control group (P < 0.001, P = 0.002). The ACR-N was 2.85 +/- 6.73 vs. -3.24 +/- 8.78 % in the control group (P < 0.001). During the first 12 weeks of treatment, 66 adverse events (AE) were reported in the Anbainuo group (15.6 %) and 21 AEs (10.5 %) occurred in the control group, whereby the rate of the Anbainuo group was slightly higher than the control group (P = 0.042). Severe adverse events (SAEs) occurred in the Anbainuo group (1.3 %) and one (SAE) occurred in the control group (0.5 %) (P = 0.19). Anbainuo displays a rapid onset of efficacy as well as good tolerance and safety in MTX-IR patients having moderate to severe RA. PMID- 27184047 TI - Outcome of a glucocorticoid discontinuation regimen in patients with inactive systemic sclerosis. AB - Glucocorticoids (GC) are widely used to treat systemic sclerosis (SSc). The lack of efficacy data and patient/physician concerns may prompt therapy discontinuation. The aim of this study is to identify factors hampering GC discontinuation in patients with stable disease on oral GC for longer than 12 months. Consecutive patients fulfilling the 2013 ACR/EULAR criteria for SSc and with stable disease were prescribed a slow tapering GC regimen to achieve discontinuation. At study entry and 6 months later (T6), patients were assessed for disease activity and severity. Moreover, the Short-Form-36; the Health Assessment Questionnaire Disability Index (HAQ-DI); and visual analog scales for fatigue, pain, and general health were completed. Reasons for stopping the discontinuation regimen were recorded. Forty-eight patients (46 females, 9 diffuse SSc), with a mean +/- SD age of 56+/-14 years and a median disease duration of 10 years (range 2-22), were enrolled. The median daily GC dose was 5 mg (range 5-10; all patients treated with prednisone). At T6, 33 (68.7 %) patients had discontinued GC. The remaining 15 patients could not discontinue GC because of arthralgia in eight, arthritis in two, puffy fingers in two, increased creatine-kinase in two, and bursitis in one patient. At multiple logistic analysis, a higher baseline HAQ-DI was the only independent factor associated with GC need (OR 2.98, 95 % CI 1.20-7.41; p = 0.01). About one third of SSc patients did not achieve a GC-free regimen. Disability as assessed by HAQ-DI was the leading factor hindering GC discontinuation. A low HAQ-DI score can identify candidates for GC discontinuation. PMID- 27184048 TI - Improving skills in pediatric rheumatology in Colombia: a combined educational strategy supported by ILAR. AB - Colombia is a densely populated country with a small number of pediatric rheumatology specialists, including 14 specialists for a population of 1,927,000 children in 2014. The objective of the study was to improve the skills required for early identification, timely referral, and management of musculoskeletal diseases, especially juvenile idiopathic arthritis (JIA), in a group of pediatricians and pediatric residents in a remote region of Colombia. Supported by grant programs developed by the International League of Associations for Rheumatology (ILAR), a combined educational strategy (blended learning) was implemented based on two classroom educational activities and four online modules. The students' acquired knowledge and perception of the strategy were evaluated. Scores were reported as median values and interquartile ranges (IQR), and the differences between scores were estimated using the Wilcoxon test for equal medians. Forty-one students were enrolled, 37 completed the online modules, and 33 attended the final in-person session. The results of the written tests demonstrated an improved ability to solve clinical problems compared with the results of the tests before the course (the median initial vs. final test scores 3 (IQR = 1) vs. 5 (IQR = 0), p = 0.000). The students reported high levels of satisfaction related to compliance with the proposed objectives, the relevance of the contents and activities performed, and the impact on everyday practice. These types of strategies are useful as tools for continuing medical education. However, the results pertain only to short-term learning. It is necessary to evaluate their impact on "lifelong learning." PMID- 27184049 TI - Type 2 diabetes, insulin treatment and prognosis of breast cancer. AB - BACKGROUND: The aim of our study was to investigate whether pre-existing type 2 diabetes and insulin therapy have an impact on the prognosis of breast cancer patients. METHODS: We performed a retrospective analysis of 462 type 2 diabetic breast cancer patients and 1644 non-diabetic breast cancer patients treated in our institute from January 2005 to August 2010. Patients were divided by diabetes status and insulin use. The clinicopathological characteristics and clinical outcomes of patients within 5 years following breast cancer diagnosed were analysed. RESULTS: Diabetic patients tended to have higher body mass index and higher histological grade tumours. Five-year disease-free survival and overall survival were reduced in diabetic patients (P < 0.001), and diabetes was an independent predictor for an increased risk of breast cancer relapse and death within 5 years (P < 0.001). Insulin treatment was associated with reduced 5-year disease-free survival and overall survival (P < 0.05); the risk of 5-year relapse and breast cancer mortality in the insulin group increased compared to that of non-insulin group after adjusting for age, tumour size, histological grade, oestrogen receptor, progesterone receptor, chemotherapy and hormone therapy (P < 0.05). After adjusting for age and other factors, the risk of breast cancer relapse was also increased in the insulin subgroup, while the risk of breast cancer mortality did not increase statistically. CONCLUSIONS: Type 2 diabetes and insulin treatment might be independently associated with poorer prognosis of breast cancer. However, caution is needed when interpreting our results, and further investigations are needed. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27184051 TI - Nmnat 1: a Security Guard of Retinal Ganglion Cells (RGCs) in Response to High Glucose Stress. AB - BACKGROUND/AIMS: Retinal neurodegeneration is an early event in the pathological process of diabetic retinopathy (DR). Retinal ganglion cell (RGC) injury is an important pathological feature during neurodegenerative process. Protecting RGCs from high glucose-induced injury is a promising strategy for delaying or hindering diabetes mellitus-related retinal neuropathy. This study aims to investigate the role of Nmnat1, an enzyme which catalyzes a key step in the biosynthesis of nicotinamide adenine dinucleotide (NAD), in high glucose-induced RGC injury. METHODS: Western blot and immunofluorescence analysis was conducted to detect Nmnat1 expression pattern in the retina and RGC-5 cell. MTT assay, Hoechst staining, trypan blue staining, and calcein-AM/ propidium iodide (PI) staining was conducted to determine the effect of Nmnat1 knockdown on RGC-5 cell function. Microarray and bioinformatics analysis was conducted to identify potential signaling pathways affected by Nmnat1 knockdown. Pharmacological intervention, molecular intervention, and in vitro experiments were conducted to reveal molecular mechanism of Nmnat1-mediated protective effect on RGC-5 cell function. RESULTS: Nmnat1 is constitutively expressed in retina and RGC-5 cells. Nmnat1 knockdown aggravates RGC injury, and accelerates the development of RGC-5 cell apoptosis upon high glucose stress. MAPK signaling is the primary signaling pathway affected by Nmnat1 knockdown. Under high glucose stress, Nmnat1 knockdown leads to p38-MAPK signaling inactivation. p38-MAPK pathway inhibitor strongly blocks Nmnat1-mediated protective effect on RGC-5 cell function. CONCLUSION: Nmnat1 protects RGC against high glucose-induced injury via p38-MAPK signaling pathway. Nmnat1 may serve as a neuroprotective target for diabetes mellitus related retinal neuropathy. PMID- 27184050 TI - Electronic cigarettes: a survey of perceived patient use and attitudes among members of the British thoracic oncology group. AB - BACKGROUND: Smoking cessation following lung cancer diagnosis has been found to improve several patient outcomes. Electronic cigarette (e-cigarette) use is now prevalent within Great Britain, however, use and practice among patients with lung cancer has not as yet been explored. The current study aims to explore e cigarette use among patients and examine current practice among clinicians. The results have important implications for future policy and practice. METHODS: Members of The British Thoracic Oncology Group (BTOG) were contacted via several e-circulations (N = 2,009), requesting them to complete an online survey. Of these, 7.7 % (N = 154) completed the survey, which explored participant demographics and smoking history, perceptions of patient e-cigarette use, practitioner knowledge regarding sources of guidance pertaining to e-cigarettes, and practitioner advice. RESULTS: Practitioners frequently observed e-cigarette use among patients with lung cancer. The majority of practitioners (81.4 %) reported responding to patient queries pertaining to e-cigarettes within the past year; however, far fewer (21.0 %) felt confident providing patients with e cigarette advice. Practitioner confidence was found to differentiate by gender (p = 0.012) and employment speciality (p = 0.030), with nurses reporting particularly low levels of confidence in advising. The results also demonstrate extensive variability regarding the practitioner advice content. CONCLUSIONS: The results demonstrate that patients refer to practitioners as a source of e cigarette guidance, yet few practitioners feel confident advising. The absence of evidence-based guidance may have contributed towards the exhibited inconsistencies in practitioner advice. The findings highlight that training should be delivered to equip practitioners with the knowledge and confidence to advise patients effectively; this could subsequently improve smoking cessation rates and patient outcomes. PMID- 27184052 TI - Understanding help-seeking intentions in male military cadets: An application of perceptual mapping. AB - BACKGROUND: Research suggests that men are less likely to seek help for depression, substance abuse, and stressful life events due to negative perceptions of asking for and receiving help. This may be exacerbated in male military cadets who exhibit higher levels of gender role conflict because of military culture. METHODS: This exploratory study examined the perceptions of 78 male military cadets toward help-seeking behaviors. Cadets completed the 31-item Barriers to Help Seeking Scale (BHSS) and a component factor analysis was used to generate five composite variables and compare to validated factors. Perceptual mapping and vector modeling, which produce 3-dimensional models of a group's perceptions, were then used to model how they conceptualize help-seeking. RESULTS: Factor analysis showed slightly different groupings than the BHSS, perhaps attributed to different characteristics of respondents, who are situated in a military school compared to general university males. Perceptual maps show that cadets perceive trust of doctors closest to them and help-seeking farthest, supporting the concept that these males have rigid beliefs about having control and its relationship to health seeking. Differences were seen when comparing maps of White and non-White cadets. White cadets positioned themselves far away from all variables, while non-White cadets were closest to "emotional control". CONCLUSION: To move these cadets toward help-seeking, vector modeling suggests that interventions should focus on their general trust of doctors, accepting lack of control, and decreasing feelings of weakness when asking for help. For non White cadets a focus on self-reliance may also need to be emphasized. Use of these unique methods resulted in articulation of specific barriers that if addressed early, may have lasting effects on help-seeking behavior as these young men become adults. Future studies are needed to develop and test specific interventions to promote help-seeking among military cadets. PMID- 27184053 TI - Neutrophil/lymphocyte ratio has a prognostic value for patients with terminal cancer. AB - BACKGROUND: Determining prognosis in advanced cancer is of key importance. Various prognostic scores have been developed. However, they are often very complex. In this study, we evaluated the feasibility of neutrophil/lymphocyte ratio (NLR) as an index to estimate survival in terminal cancer patients. METHODS: NLR was calculated retrospectively based on blood tests performed at 3 months, 2 months, 4 weeks, 3 weeks, 2 weeks, 1 week, and within 3 days before death in 160 cancer patients (82 men, 78 women; age range, 33-99 years; mean age, 69.8 years). RESULTS: NLR increased significantly with time (P < 0.0001). Mean NLR was significantly higher in patients who died within 4 weeks (29.82) than in those who lived more than 4 weeks (6.15). The NLR cutoff point was set at 9.21 according to receiver operating characteristic curve analysis (area under the curve, 0.82; 95% confidence interval, 0.79-0.85). We inferred that life expectancy would be <4 weeks when NLR >9.21. The sensitivity, specificity, positive predictive value, and negative predictive value were 65.6, 84.1, 90.6, and 51.1%, respectively. The positive and negative likelihood ratios were 4.125 and 0.409, respectively. CONCLUSIONS: NLR appears to be a useful and simple parameter to predict the clinical outcomes of patients with terminal cancer. PMID- 27184055 TI - Early detection of local recurrence after soft tissue sarcoma resection and flap reconstruction. AB - PURPOSE: Flap reconstruction has become an essential component in soft tissue sarcoma treatment. However, the clinical features of local recurrence after soft tissue sarcoma resection and flap reconstruction remain unclear. The present study aimed to establish effective follow-up strategies after soft tissue sarcoma resection and flap reconstruction. METHODS: Data from patients who underwent soft tissue sarcoma resection and immediate flap reconstruction were retrospectively reviewed. Follow-up after surgery included history taking and physical examination during every visit to the hospital. Magnetic resonance imaging to evaluate the primary site was performed six months after the end of treatment then annually for ten years. The methods of detection of local recurrence were assessed. RESULTS: A total of 229 consecutive patients were included in the present study. During a median follow-up period of 40 months, 33 patients (14.4%) developed local recurrence. Twenty-three recurrences that occurred on the margin of the transferred flap were detected as palpable mass prior to radiological assessment; among the remaining ten recurrences that occurred in the deep layer of the transferred flap, six were detected by abnormal clinical findings and four were clinically occult and detected by surveillance radiological assessment. CONCLUSIONS: Surveillance radiological assessment has an important role in early detection of local recurrence that develops in the deep layer of the transferred flap. Therefore, meticulous clinical assessment combined with routine radiological study should be performed during follow-up evaluation for local recurrence after soft tissue sarcoma resection and flap reconstruction. PMID- 27184054 TI - Single-cell antibody nanowells: a novel technology in detecting anti-SSA/Ro60- and anti-SSB/La autoantibody-producing cells in peripheral blood of rheumatic disease patients. AB - BACKGROUND: Anti-SSA/Ro60 and anti-SSB/La are essential serological biomarkers for rheumatic diseases, specifically Sjogren's syndrome (SS) and systemic lupus erythematosus (SLE). Currently, laboratory detection technology and platforms are designed with an emphasis on high-throughput methodology; therefore, the relationship of sensitivity with specificity remains a significant area for improvement. In this study, we used single-cell antibody nanowells (SCAN) technology to directly profile individual B cells producing antibodies against specific autoantigens such as SSA/Ro60 and SSB/La. METHODS: Peripheral blood mononuclear cells were isolated using Ficoll gradient. Fluorescently labeled cells were added to fabricated nanowells and imaged using a high-speed epifluorescence microscope. The microengraving process was conducted using printed slides coated with immunoglobulins. Printed slides were hybridized with fluorescence-conjugated immunoglobulin G (IgG), SSA/Ro60, and SSB/La antigens. Microarray spots were analyzed for nanowells with single live B cells that produced antigen-specific autoantibodies. RESULTS: Our results indicate that SCAN can simultaneously detect high frequencies of anti-SSA/Ro60 and anti-SSB/La with a specific IgG isotype in peripheral blood mononuclear cells of patients, as well as measure their individual secretion levels. The data showed that patients with SS and SLE exhibited higher frequency and greater concentration of anti-SSA/Ro60- and anti-SSB/La-producing B cells in the IgG isotype. Furthermore, individual B cells of patients produced higher levels of IgG-specific anti-SSA/Ro60 autoantibody, but not IgG-specific anti-SSB/La autoantibody, compared with healthy control subjects. CONCLUSIONS: These results support the application of SCAN as a robust multiparametric analytical bioassay that can directly measure secretion of autoantibody and accurately report antigen-specific, autoantibody producing cells. PMID- 27184056 TI - Value-modulated oculomotor capture by task-irrelevant stimuli is a consequence of early competition on the saccade map. AB - Recent research has shown that reward learning can modulate oculomotor and attentional capture by physically salient and task-irrelevant distractor stimuli, even when directing gaze to those stimuli is directly counterproductive to receiving reward. This value-modulated oculomotor capture effect may reflect biased competition in the oculomotor system, such that the relationship between a stimulus feature and reward enhances that feature's representation on an internal priority map. However, it is also possible that this effect is a result of reward reducing the threshold for a saccade to be made to salient items. Here, we demonstrate value-modulated oculomotor capture when two reward-associated distractor stimuli are presented simultaneously in the same search display. The influence of reward on oculomotor capture is found to be most prominent at the shortest saccade latencies. We conclude that the value-modulated oculomotor capture effect is a consequence of biased competition on the saccade priority map and cannot be explained by a general reduction in saccadic threshold. PMID- 27184057 TI - The effects of aging on the perception of depth from motion parallax. AB - Successful navigation in the world requires effective visuospatial processing. Unfortunately, older adults have many visuospatial deficits, which can have severe real-world consequences. Although some of these age effects are well documented, some others, such as the perception of depth from motion parallax, are poorly understood. Depth perception from motion parallax requires intact retinal image motion and pursuit eye movement processing. Decades of research have shown that both motion processing and pursuit eye movements are affected by age; it follows that older adults may also be less sensitive to depth from motion parallax. The goals of the present study were to characterize motion parallax depth thresholds in older adults, and to explain older adults' sensitivity to depth from motion parallax in terms of motion and pursuit deficits. Younger and older adults' motion thresholds and pursuit accuracy were measured. Observers' depth thresholds across several different stimulus conditions were measured, as well. Older adults had higher motion thresholds and less accurate pursuit than younger adults. They were also less sensitive to depth from motion parallax at slow and moderate pursuit speeds. Although older adults had higher motion thresholds than younger adults, they used the available motion signals optimally, and age differences in motion processing could not account for the older adults' increased depth thresholds. Rather, these age effects can be explained by changes in older adults' pursuit signals. PMID- 27184058 TI - Alignment effects in beer mugs: Automatic action activation or response competition? AB - Responses to objects with a graspable handle are faster when the response hand and handle orientation are aligned (e.g., a key press with the right hand is required and the object handle is oriented to the right) than when they are not aligned. This effect could be explained by automatic activation of specific motor programs when an object is viewed. Alternatively, the effect could be explained by competition at the response level. Participants performed a reach-and-grasp or reach-and-button-press action with their left or right hand in response to the color of a beer mug. The alignment effect did not vary as a function of the type of action. In addition, the alignment effect disappeared in a go/no-go version of the task. The same results were obtained when participants made upright/inverted decisions, so that object shape was task-relevant. Our results indicate that alignment effects are not due to automatic motor activation of the left or right limb. PMID- 27184059 TI - Post-Traumatic Headache Therapy in the Athlete. AB - Post-traumatic headache can occur after any traumatic brain injury, regardless of severity. Headache is consistently the most common symptom following concussion and occurs in over 90% of athletes with sports-related concussion. Despite this prevalence, the complaint of headache after a possible concussive injury is often dismissed. Even when sports-related concussion is accurately diagnosed, many athletes fall victim to mismanagement of this associated symptom by clinicians who are not well-versed in headache treatment. Furthermore, benign headaches may also occur incidentally in the context of head trauma. This complex, and often non-specific, nature of headaches provides a significant challenge in return to play decision-making. Post-traumatic headaches are generally categorized according to primary headache disorders in an attempt to guide treatment; however, there is minimal medical literature on headache management in the concussed athlete. There is clearly a continued need for prospective studies of existing treatments and new approaches. PMID- 27184060 TI - The Pathophysiology of Concussion. AB - Concussion is a significant issue in medicine and the media today. With growing interest on the long-term effects of sports participation, it is important to understand what occurs in the brain after an impact of any degree. While some of the basic pathophysiology has been elucidated, much is still unknown about what happens in the brain after traumatic brain injury, particularly with milder injuries where no damage can be seen at the structural level on standard neuroimaging. Understanding the chain of events from a cellular level using studies investigating more severe injuries can help to drive research efforts in understanding the symptomatology that is seen in the acute phase after concussion, as well as point to mechanisms that may underlie persistent post concussive symptoms. This review discusses the basic neuropathology that occurs after traumatic brain injury at the cellular level. We also present the pathology of chronic traumatic encephalopathy and its similarities to other neurodegenerative diseases. We conclude with recent imaging and biomarker findings looking at changes that may occur after repeated subconcussive blows, which may help to guide efforts in understanding if cumulative subconcussive mechanical forces upon the brain are detrimental in the long term or if concussive symptoms mark the threshold for brain injury. PMID- 27184061 TI - Ultraviolet B irradiation in the prevention of alloimmunization in a dog platelet transfusion model. AB - BACKGROUND: Alloimmune platelet (PLT) refractoriness remains a significant problem for chronically transfused patients with thrombocytopenia. STUDY DESIGN AND METHODS: In a dog PLT transfusion model, we evaluated ultraviolet B irradiation (UV-B) of donor PLTs-either alone or in combination with centrifuge leukoreduction (C-LR) or filtration leukoreduction (F-LR)-to prevent refractoriness to donor PLTs and to induce tolerance to standard (STD) PLTs from the same donor or to tertiary donors. RESULTS: Recipient acceptance rates for C LR donor PLT transfusions were 14%, F-LR were 33%, and UV-B irradiated were 45% with no significant differences among the treatments given to the donor's PLTs. Adding UV-B irradiation to C-LR or F-LR PLTs increased acceptance rates to 50 and 68% (p = 0.02 and p = 0.05), respectively, comparing single treatments to the combined treatments. After a recipient had accepted any type of UV-B-treated donor PLTs, specific tolerance to subsequent transfusions of the same donor's STD PLTs averaged 65%. Nonspecific tolerance to third-party donor's STD PLTs averaged 36% if they had accepted their initial donor's treated PLTs but was only 4% (p < 0.001) if they had rejected these PLTs. CONCLUSION: Combining UV-B irradiation with a method of leukoreduction produces additive effects on prevention of alloimmune PLT refractoriness. PMID- 27184062 TI - A time for multi-scale modeling of anti-fibrotic therapies: Comment on "Towards a unified approach in the modeling of fibrosis: A review with research perspectives" by Martine Ben Amar and Carlo Bianca. PMID- 27184063 TI - The remodeling of the fibers texture Comment on "Towards a unified approach in the modeling of fibrosis: A review with research perspectives" by Martine Ben Amar and Carlo Bianca. PMID- 27184064 TI - Importance of Different Grades of Abdominal Obesity on Testosterone Level, Erectile Dysfunction, and Clinical Coincidence. AB - The aim of the current study was to investigate the influence of different grades of abdominal obesity (AO) on the prevalence of testosterone deficiency syndrome (TDS), erectile dysfunction (ED), and metabolic syndrome (MetS). In a cross sectional descriptive study, a total of 216 males underwent a complete urological, internal, and hormonal evaluation. Males were divided according to waist circumference into five groups: less than 94 cm (Grade [G] 0), 94 to 101 cm (G1), 102 to 109 cm (G2), 110 to 119 cm (G3), and more than 120 cm (G4). Incidence of ED, TDS, and MetS was compared in these groups and in participants without AO. Some degree of ED was identified in 74.7% of males with AO. In G1, there were 61% of males with ED, in G2 68%, in G3 83%, and in G4 87%. A strong correlation between testosterone (TST) level and AO was identified. Ninety-eight out of 198 (49.5%) males with AO and 1/18 (5.5%) males without AO had TDS. There were significant differences between individual groups. In the group of males with AO G4 (more than 120 cm), 87.1% had TDS. MetS was diagnosed in 105/198 (53.0%) males with AO, but in G4, 83.9% of males with AO had MetS. Males older than 40 years of age with AO have a higher incidence of ED, TDS, and MetS. Dividing males into five groups according to waist circumference seems to be reasonable. With growing AO, there were significantly more males with ED, TDS, and MetS. PMID- 27184065 TI - US warns against use of fluoroquinolones for uncomplicated infections. PMID- 27184066 TI - Decreased expression of hyaluronan synthase 1 and 2 associates with poor prognosis in cutaneous melanoma. AB - BACKGROUND: Hyaluronan is a large extracellular matrix molecule involved in several biological processes such as proliferation, migration and invasion. In many cancers, hyaluronan synthesis is altered, which implicates disease progression and metastatic potential. We have previously shown that synthesis of hyaluronan and expression of its synthases 1-2 (HAS1-2) decrease in cutaneous melanoma, compared to benign melanocytic lesions. METHODS: In the present study, we compared immunohistological staining results of HAS1 and HAS2 with clinical and histopathological parameters to investigate whether HAS1 or HAS2 has prognostic value in cutaneous melanoma. The specimens consisted of 129 tissue samples including superficial (Breslow <= 1 mm) and deep (Breslow > 4 mm) melanomas and lymph node metastases. The differences in immunostainings were analysed with non-parametric Mann-Whitney U test. Associations between immunohistological staining results and clinical parameters were determined with the chi(2) test. Survival between patient groups was compared by the Kaplan-Meier method using log rank test and Cox's regression model was used for multivariate analyses. RESULTS: The expression of HAS1 and HAS2 was decreased in deep melanomas and metastases compared to superficial melanomas. Decreased immunostaining of HAS2 in melanoma cells was significantly associated with several known unfavourable histopathologic prognostic markers like increased mitotic count, absence of tumor infiltrating lymphocytes and the nodular subtype. Furthermore, reduced HAS1 and HAS2 immunostaining in the melanoma cells was associated with increased recurrence of melanoma (p = 0.041 and p = 0.006, respectively) and shortened disease- specific survival (p = 0.013 and p = 0.001, respectively). CONCLUSIONS: This study indicates that reduced expression of HAS1 and HAS2 is associated with melanoma progression and suggests that HAS1 and HAS2 have a prognostic significance in cutaneous melanoma. PMID- 27184067 TI - CD11c.DTR mice develop a fatal fulminant myocarditis after local or systemic treatment with diphtheria toxin. AB - To assess the role of alveolar macrophages (AMs) during a pulmonary Aspergillus fumigatus infection AMs were depleted by intratracheal application of diphtheria toxin (DTX) to transgenic CD11c.DTR mice prior to fungal infection. Unexpectedly, all CD11c.DTR mice treated with DTX died within 4-5 days, whether being infected with A. fumigatus or not. Despite measurable impact of DTX on lung functional parameters, these constrictions could not explain the high mortality rate. Instead, DTX-treated CD11c.DTR animals developed fulminant myocarditis (FM) characterized by massive leukocyte infiltration and myocardial cell destruction, including central parts of the heart's stimulus transmission system. In fact, standard limb lead ECG recordings of diseased but not healthy mice showed a "Brugada"-like pattern with an abnormally high ST segment pointing to enhanced susceptibility for potential lethal arrhythmias. While CD11c.DTR mice are extensively used for the characterization of CD11c(+) cells, including dendritic cells, several studies have already mentioned adverse side effects following DTX treatment. Our results demonstrate that this limitation is based on severe myocarditis but not on the expected lung constrictions, and has to be taken into consideration if this animal model is used. Based on these properties, however, the CD11c.DTR mouse might serve as useful animal model for FM. PMID- 27184068 TI - A Feasibility Study Showing [68Ga]Citrate PET Detects Prostate Cancer. AB - PURPOSE: The management of advanced or recurrent prostate cancer is limited in part by the lack of effective imaging agents. Metabolic changes in prostate cancer have previously been exploited for imaging, culminating in the recent US FDA approval of [11C]choline for the detection of subclinical recurrent disease after definitive local therapy. Despite this milestone, production of [11C]choline requires an on-site cyclotron, limiting the scope of medical centers at which this scan can be offered. In this pilot study, we tested whether prostate cancer could be imaged with positron emission tomography (PET) using [68Ga]citrate, a radiotracer that targets iron metabolism but is produced without a cyclotron. PROCEDURES: Eight patients with castrate-resistant prostate cancer were enrolled in this single-center feasibility study. All patients had evidence of metastatic disease by standard of care imaging [X-ray computed tomography (CT), bone scan, or magnetic resonance imaging (MRI)] prior to PET with [68Ga]citrate. Patients were intravenously injected with increasing doses of [68Ga]citrate (136.9 to a maximum of 259 MBq). Uptake time was steadily increased from 1 h to approximately 3.5 h for the final 4 patients, and all patients were imaged with a PET/MRI. Qualitative and semi-quantitative (maximum standardized uptake value (SUVmax)) assessment of the metastatic lesions was performed and compared to the standard of care imaging. RESULTS: At 1- and 2-h imaging times post injection, there were no detectable lesions with [68Ga]citrate PET. At 3- to 4-h uptake time, there were a total of 71 [68Ga]citrate-positive lesions (67 osseous, 1 liver, and 3 lymph node). Of these, 65 lesions were visible on the standard of care imaging (CT and/or bone scan). One PET-avid osseous vertebral body metastasis was not apparent on either CT or bone scan. Twenty-five lesions were not PET-avid but seen on CT and bone scan (17 bone, 6 lymph node, 1 pleural, and 1 liver). The average of the maximum SUVs for bone or soft tissue metastases for patients treated at higher doses and uptake time was statistically higher than the corresponding parameter in normal liver, muscle, and bone. Visually obvious blood pool activity was observed even 3-4 h post injection, suggesting that further optimization of the [68Ga]citrate imaging protocol is required to maximize signal-to-background ratios. CONCLUSIONS: Our preliminary results support that PET with [68Ga]citrate may be a novel tool for imaging prostate cancer. Future studies are needed to determine the optimal imaging protocol, the clinical significance of [68Ga]citrate uptake, and its role in therapeutic decisions. PMID- 27184069 TI - The Past, Present, and Future of Genetic Manipulation in Toxoplasma gondii. AB - Toxoplasma gondii is a classic model for studying obligate intracellular microorganisms as various genetic manipulation tools have been developed in T. gondii over the past 20 years. Here we summarize the major strategies for T. gondii genetic manipulation including genetic crosses, insertional mutagenesis, chemical mutagenesis, homologous gene replacement, conditional knockdown techniques, and the recently developed clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system. We evaluate the advantages and limitations of each of these tools in a historical perspective. We also discuss additional applications of modified CRISPR-Cas9 systems for use in T. gondii, such as regulation of gene expression, labeling of specific genomic loci, and epigenetic modifications. These approaches have the potential to revolutionize the analysis of T. gondii biology and help us to better develop new drugs and vaccines. PMID- 27184070 TI - Reward positivity: Reward prediction error or salience prediction error? AB - The reward positivity is a component of the human ERP elicited by feedback stimuli in trial-and-error learning and guessing tasks. A prominent theory holds that the reward positivity reflects a reward prediction error signal that is sensitive to outcome valence, being larger for unexpected positive events relative to unexpected negative events (Holroyd & Coles, 2002). Although the theory has found substantial empirical support, most of these studies have utilized either monetary or performance feedback to test the hypothesis. However, in apparent contradiction to the theory, a recent study found that unexpected physical punishments also elicit the reward positivity (Talmi, Atkinson, & El Deredy, 2013). The authors of this report argued that the reward positivity reflects a salience prediction error rather than a reward prediction error. To investigate this finding further, in the present study participants navigated a virtual T maze and received feedback on each trial under two conditions. In a reward condition, the feedback indicated that they would either receive a monetary reward or not and in a punishment condition the feedback indicated that they would receive a small shock or not. We found that the feedback stimuli elicited a typical reward positivity in the reward condition and an apparently delayed reward positivity in the punishment condition. Importantly, this signal was more positive to the stimuli that predicted the omission of a possible punishment relative to stimuli that predicted a forthcoming punishment, which is inconsistent with the salience hypothesis. PMID- 27184071 TI - Highly Integrated Supercapacitor-Sensor Systems via Material and Geometry Design. AB - An ultimate integration strategy making use of material and geometry is applied in a proof-of-concept study. Integrated supercapacitor-sensor systems with the capability of photodetecting and strain sensing are fabricated based on multifunctional conducting polypyrrole and piezoresistive textile geometry, respectively. This integration strategy enables promising applications for self powered smart sensory, wearable and healthcare electronics. PMID- 27184072 TI - St George Acute Care Team: the local variant of crisis resolution model of care. AB - OBJECTIVES: The objective of this study was to describe functioning and clinical activities of the St George Acute Care Team and how it compares to the typical crisis resolution model of care. METHODS: Descriptive data including demographics, sources of referral, type of clinical intervention, length of stay, diagnoses and outcomes were collected from records of all patients who were discharged from the team during a 10 week period. RESULTS: There were 677 referrals. The team's functions consisted of post-discharge follow-up (31%), triage and intake (30%), case management support (23%) and acute community based assessment and treatment (16%). The average length of stay was 5 days. The majority of patients were diagnosed with a mood (23%) or a psychotic (25%) disorder. Points of contrast to other reported crisis resolution teams include shorter length of stay, relatively less focus on direct clinical assessment and more telephone follow-up and triage. CONCLUSION: St George Acute Care Team provides a variety of clinical activities. The focus has shifted away from the original model of crisis resolution care to meet local and governmental requirements. PMID- 27184073 TI - Dominant factors limiting the optical gain in layered two-dimensional halide perovskite thin films. AB - Semiconductors are ubiquitous gain media for coherent light sources. Solution processed three-dimensional (3D) halide perovskites (e.g., CH3NH3PbI3) with their outstanding room temperature optical gain properties are the latest members of this family. Their two-dimensional (2D) layered perovskite counterparts with natural multiple quantum well structures exhibit strong light-matter interactions and intense excitonic luminescence. However, despite such promising traits, there have been no reports on room temperature optical gain in 2D layered perovskites. Herein, we reveal the challenges towards achieving amplified spontaneous emission (ASE) in the archetypal (C6H5C2H4NH3)2PbI4 (or PEPI) system. Temperature dependent transient spectroscopy uncovers the dominant free exciton trapping and bound biexciton formation pathways that compete effectively with biexcitonic gain. Phenomenological rate equation modeling predicts a large biexciton ASE threshold of ~1.4 mJ cm(-2), which is beyond the damage threshold of these materials. Importantly, these findings would rationalize the difficulties in achieving optical gain in 2D perovskites and provide new insights and suggestions for overcoming these challenges. PMID- 27184074 TI - A novel procedure for the assessment of the antioxidant capacity of food components. AB - Carbonylation, an oxidative modification of the amino group of arginine and lysine residues caused by reactive oxygen species, has emerged as a new type of oxidative damage. Protein carbonylation has been shown to exert adverse effects on various protein functions. Recently, the role of food components in the attenuation of oxidative stress has been the focus of many studies. Most of these studies focused on the chemical properties of food components. However, it is also important to determine their effects on protein functions via post translational modifications. In this study, we developed a novel procedure for evaluating the antioxidant capacity of food components. Hydrogen peroxide (H2O2) induced protein carbonylation in HL-60 cells was quantitatively analyzed by using fluorescent dyes (Cy5-hydrazide dye and IC3-OSu dye), followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and fluorescence determination. Among a panel of food components tested, quinic acid, kaempferol, saponin, squalene, trigonelline, and mangiferin were shown to be capable of suppressing protein carbonylation in HL-60 cells. Our results demonstrated that this fluorescence labeling/SDS-PAGE procedure allows for the detection of oxidative stress-induced protein carbonylation with high sensitivity and quantitative accuracy. This method should be useful for the screening of new antioxidant food components as well as the analysis of their suppression mechanism. PMID- 27184075 TI - Mesorectal node metastasis from gynecological cancer in the era of 3D conformal pelvic radiation therapy and intensity modulated radiation therapy. PMID- 27184076 TI - The gain-of-function enhancement of IP3-receptor channel gating by familial Alzheimer's disease-linked presenilin mutants increases the open probability of mitochondrial permeability transition pore. AB - Mutants in presenilins (PS1 or PS2) are the major cause of familial Alzheimer's disease (FAD). They affect intracellular Ca(2+) homeostasis by increasing the open probability (Po) of inositol 1,4,5-trisposphate (IP3) receptor (IP3R) Ca(2+) release channel located on the endoplasmic reticulum (ER) leading to exaggerated Ca(2+) release into a cytoplasmic microdomain formed by neighboring cluster of a few IP3R channels and mitochondrial Ca(2+) uniporter (MCU). Ca(2+) concentration in the microdomain ( [Formula: see text] ) depends on the distance between the cluster and MCU (r); the number of IP3R in the cluster releasing Ca(2+) to the cytoplasm ( [Formula: see text] ), and Po of IP3R. Using experimental whole-cell IP3R-mediated cytosolic Ca(2+) data, in conjunction with a computational model of cell bioenergetics, a data-driven Markov chain model for IP3R gating, and a model for the dynamics of the mitochondrial permeability transition pore (PTP), we explore differences in mitochondrial Ca(2+) uptake in cells expressing wild type (PS1-WT) and FAD-causing mutant (PS1-M146L) PS. We find that increased mitochondrial [Formula: see text] due to the gain-of-function enhancement of IP3R channels in the cells expressing PS1-M146L leads to the opening of PTP in high conductance state (PTPh), where the latency of opening is inversely correlated with r and proportional to [Formula: see text] . Furthermore, we observe diminished inner mitochondrial membrane potential (DeltaPsim), [NADH], [Formula: see text] , and [ATP] when PTP opens. Additionally, we explore how parameters such as the pH gradient, inorganic phosphate concentration, and the rate of the Na(+)/Ca(2+)-exchanger affect the latency of PTP to open in PTPh. PMID- 27184079 TI - In Vivo Mapping of Eukaryotic RNA Interactomes Reveals Principles of Higher-Order Organization and Regulation. AB - Identifying pairwise RNA-RNA interactions is key to understanding how RNAs fold and interact with other RNAs inside the cell. We present a high-throughput approach, sequencing of psoralen crosslinked, ligated, and selected hybrids (SPLASH), that maps pairwise RNA interactions in vivo with high sensitivity and specificity, genome-wide. Applying SPLASH to human and yeast transcriptomes revealed the diversity and dynamics of thousands of long-range intra- and intermolecular RNA-RNA interactions. Our analysis highlighted key structural features of RNA classes, including the modular organization of mRNAs, its impact on translation and decay, and the enrichment of long-range interactions in noncoding RNAs. Additionally, intermolecular mRNA interactions were organized into network clusters and were remodeled during cellular differentiation. We also identified hundreds of known and new snoRNA-rRNA binding sites, expanding our knowledge of rRNA biogenesis. These results highlight the underexplored complexity of RNA interactomes and pave the way to better understanding how RNA organization impacts biology. PMID- 27184080 TI - Global Mapping of Human RNA-RNA Interactions. AB - The majority of the human genome is transcribed into non-coding (nc)RNAs that lack known biological functions or else are only partially characterized. Numerous characterized ncRNAs function via base pairing with target RNA sequences to direct their biological activities, which include critical roles in RNA processing, modification, turnover, and translation. To define roles for ncRNAs, we have developed a method enabling the global-scale mapping of RNA-RNA duplexes crosslinked in vivo, "LIGation of interacting RNA followed by high-throughput sequencing" (LIGR-seq). Applying this method in human cells reveals a remarkable landscape of RNA-RNA interactions involving all major classes of ncRNA and mRNA. LIGR-seq data reveal unexpected interactions between small nucleolar (sno)RNAs and mRNAs, including those involving the orphan C/D box snoRNA, SNORD83B, that control steady-state levels of its target mRNAs. LIGR-seq thus represents a powerful approach for illuminating the functions of the myriad of uncharacterized RNAs that act via base-pairing interactions. PMID- 27184077 TI - U2AF35(S34F) Promotes Transformation by Directing Aberrant ATG7 Pre-mRNA 3' End Formation. AB - Recurrent mutations in the splicing factor U2AF35 are found in several cancers and myelodysplastic syndrome (MDS). How oncogenic U2AF35 mutants promote transformation remains to be determined. Here we derive cell lines transformed by the oncogenic U2AF35(S34F) mutant and identify aberrantly processed pre-mRNAs by deep sequencing. We find that in U2AF35(S34F)-transformed cells the autophagy related factor 7 (Atg7) pre-mRNA is abnormally processed, which unexpectedly is not due to altered splicing but rather selection of a distal cleavage and polyadenylation (CP) site. This longer Atg7 mRNA is translated inefficiently, leading to decreased ATG7 levels and an autophagy defect that predisposes cells to secondary mutations, resulting in transformation. MDS and acute myeloid leukemia patient samples harboring U2AF35(S34F) have a similar increased use of the ATG7 distal CP site, and previous studies have shown that mice with hematopoietic cells lacking Atg7 develop an MDS-like syndrome. Collectively, our results reveal a basis for U2AF35(S34F) oncogenic activity. PMID- 27184081 TI - Identification and molecular docking studies for novel inverse agonists of SREB, super conserved receptor expressed in brain. AB - The identification of novel synthetic ligands for G protein-coupled receptors (GPCRs) is important not only for understanding human physiology, but also for the development of novel drugs, especially for orphan GPCRs for which endogenous ligands are unknown. One of the orphan GPCR subfamilies, Super conserved Receptor Expressed in Brain (SREB), consists of GPR27, GPR85 and GPR173 and is expressed in the central nervous system. We report herein the identification of inverse agonists for the SREB family without their agonists. We carried out an in vitro screening of 5472 chemical compounds from the RIKEN NPDepo chemical library. The binding of [(35) S]GTPgammaS to the GPR173-Gsalpha fusion protein expressed in Sf9 cells was measured and resulted in the identification of 8 novel GPR173 inverse agonists. The most potent compound showed an IC50 of approximately 8 MUm. The identified compounds were also antagonists for other SREB members, GPR27 and GPR85. These results indicated that the SREB family could couple Gs-type G proteins, and SREB-Gsalpha fusion proteins showed significant constitutive activities. Moreover, a molecular model of GPR173 was constructed using the screening results. The combination of computational and biological methods will provide a unique approach to ligand identification for orphan GPCRs and brain research. PMID- 27184078 TI - Activation of Mitofusin2 by Smad2-RIN1 Complex during Mitochondrial Fusion. AB - Smads are nuclear-shuttling transcriptional mediators of transforming growth factor-beta (TGF-beta) signaling. Although their essential nuclear roles in gene regulation during development and carcinogenesis are well established, whether they have important cytoplasmic functions remains unclear. Here we report that Smad2 is a critical determinant of mitochondrial dynamics. We identified mitofusin2 (MFN2) and Rab and Ras Interactor 1 (RIN1) as new Smad2 binding partners required for mitochondrial fusion. Unlike TGF-beta-induced Smad2/3 transcriptional responses underlying mitochondrial fragmentation and apoptosis, inactive cytoplasmic Smad2 rapidly promotes mitochondrial fusion by recruiting RIN1 into a complex with MFN2. We demonstrate that Smad2 is a key scaffold, allowing RIN1 to act as a GTP exchange factor for MFN2-GTPase activation to promote mitochondrial ATP synthesis and suppress superoxide production. These results reveal functional implications between Smads and mitochondrial dysfunction in cancer and metabolic and neurodegenerative disorders. PMID- 27184082 TI - Collegium Ramazzini: Comments on the 2014 Helsinki consensus report on asbestos. PMID- 27184084 TI - Variation in antral follicle counts at different times in the menstrual cycle: does it matter? AB - Antral follicle count (AFC) variation was examined across the menstural cycle and its effect on clinical management assessed. In 79 women, AFC was documented in early (iAFC) and late follicular phase (sAFC). Absolute agreement between iAFC and sAFC and agreement for classification into categories of risk of extremes of ovarian response were examined. Ovarian stimulation protocols designed with iAFC and sAFC, and the predictive value of iAFC and sAFC for extremes of ovarian response, were compared in women undergoing ovarian stimulation. Significant differences were found between iAFC and sAFC (16 [IQR 9-24] versus 13 [IQR 7- 21]; P = 0.001), with moderate agreement for the classification into at risk of extremes of response (k = 0.525). Agreement for protocol selection based on either AFC (k = 0.750) and starting gonadotrophin dose was good (concordance correlation coefficient 0.970 [95% CI 0.951 to 0.982]). Predictive value for iAFC and sAFC was maintained for poor ovarian response and risk of ovarian hyperstimulation syndrome (OR 0.634 [0.427 to 0.920], 0.467 [0.233 to 0.935]) and (OR 1.049 [0.974 to 1.131], 1.140 [1.011 to 1.285]). Across the cycle, AFC varies but does not significantly affect ovarian stimulation protocol design and prediction of extreme ovarian response. PMID- 27184083 TI - Detection of Serum Interleukin-6/10/18 Levels in Sepsis and Its Clinical Significance. AB - OBJECTIVE: To explore the clinical significance of serum levels of IL-6/10/18 in sepsis. METHODS: Sixty-six patients with sepsis were selected to be the case group. Additionally, 42 healthy adults were selected to be the control group. ELISA was used to measure the serum levels of IL-6/10/18, and ROC was utilized to evaluate the diagnostic values of IL-6/10/18 in sepsis. RESULTS: The heart rate, respiratory rate, WBC count and APACHE II score in the sepsis group were significantly higher than those in the control group, and these indexes were increased in turn in the mild sepsis group, severe sepsis group, and septic shock group (all P < 0.05 after correction). The serum IL-6/18 levels in sepsis patients were significantly higher than those in the control group, and both of the levels were increased in turn in the mild sepsis group, severe sepsis group, and septic shock group (both P < 0.05). However, no significant difference was found in serum IL-10 level between groups (P > 0.05). The cut-off points of IL-6 and IL-18 were 109.19 pg/ml (sensitivity: 94.4%; specificity: 83.3%) and 116.01 pg/ml (sensitivity: 77.8%; specificity: 83.3%), respectively. Serum IL-6 levels were positively correlated with the APACHE II score and heart rate (both P < 0.001). CONCLUSION: Serum levels of IL-6/8 are up-regulated in sepsis patients. Additionally, IL-6 has a greater sensitivity than IL-18. Serum IL-6 levels were positively correlated with the APACHE II score and heart rate, indicating that IL 6 could be used as a potential biomarker for sepsis. PMID- 27184085 TI - The precision of bacterial quantification techniques on different kinds of environmental samples and the effect of ultrasonic treatment. AB - The precision of cell number quantification in environmental samples depends on the complexity of the sample and on the applied technique. We compared fluorescence microscopy after filtration, quantification of gene copies and the cultivation based most probable number technique for their precision. We further analyzed the effect of increasing complexity of the sample material on the precision of the different methods by using pure cultures of Pseudomonas aeruginosa, fresh water samples and sediment slurries with and without ultrasonic treatment for analyses. Microscopy reached the highest precision, which was similar between pure cultures and water samples, but lower for sediment samples due to a higher percentage of cells in clusters and flocks. The PCR based quantification was most precise for pure cultures. Water and sediment samples were similar but less precise, which might be caused by the applied DNA extraction techniques. MPN measurements were equally precise for pure cultures and water samples. For sediment slurries the precision was slightly lower. The applied ultrasonic treatment of the slurries dispersed the cell clusters and flocks, increased the precision of microscopical and MPN measurements and also increased the number of potential colony forming units. However, the culturable cell number decreased by half. For MPN quantification of viable cells in samples with a high proportion of clustered cells we therefore recommend an optimization of ultrasonic treatment and a confirmation by microscopy and cultivation to reach highest possible dispersion of the cells with a minimum of inactivation. As a result of these observations we suggest a correction factor for MPN measurements to consider the effect of sonication on complex samples. The results are most likely applicable to other complex samples such as soil or biofilms. PMID- 27184086 TI - A simultaneous two-colour detection method of human IgG- and IgE-reactive proteins from lactic acid bacteria. AB - Whole cell extracts of two Lactobacillus strains were tested with primary antibodies from two pooled sera from allergic patients. Fluorescently labelled anti-human IgG and anti-human IgE secondary antibodies applied in Western blotting, together with an appropriate image acquisition protocol facilitated imagining bacterial proteins that reacted with human IgG and IgE. PMID- 27184088 TI - Antibiotic prophylaxis for cardiac surgery in a setting with high prevalence of extended-spectrum beta-lactamase-producing Gram-negative bacteria. PMID- 27184087 TI - Whole-genome sequencing as standard practice for the analysis of clonality in outbreaks of meticillin-resistant Staphylococcus aureus in a paediatric setting. AB - Meticillin-resistant Staphylococcus aureus (MRSA) is one of the leading causes of hospital-associated infections. This study investigated the potential use of whole-genome sequencing (WGS) for surveillance purposes by re-examining MRSA strains related to past outbreaks among hospitalized paediatric patients. WGS data ameliorated the genotypic profile previously obtained with Sanger sequencing and pulsed-field gel electrophoresis typing, and discriminated between strains that were related and unrelated to the outbreaks. This allowed strain clonality to be defined with a higher level of resolution than achieved previously. This study demonstrates the potential of WGS to trace hospital outbreaks, which may lead to WGS becoming standard practice in outbreak investigations. PMID- 27184089 TI - Anterior spinal artery syndrome after spinal anaesthesia for caesarean delivery with normal lumbar and thoracic magnetic resonance imaging. PMID- 27184090 TI - First total synthesis of (+)-broussonetine W: glycosidase inhibition of natural product & analogs. AB - The first total synthesis of (+)-broussonetine W (4), a naturally-occurring pyrrolidine iminosugar isolated from the traditional Chinese medical plant Broussonetia kazinoki SIEB (Moraceae), has been completed through a concise synthetic route starting from the readily available d-arabinose derived cyclic nitrone 10 in 11 steps and 31% overall yield, with regioselective installation of the alpha,beta-unsaturated ketone functional group by the elimination of HBr from alpha-bromoketone as the key step. A number of analogs of (+)-broussonetine W (4) with variable side chain length, different polyhydroxylated pyrrolidine core configurations or saturated cyclohexanones have also been prepared to explore the glycosidase inhibition and the preliminary structure-activity relationship of this intriguing class of compounds. Glycosidase inhibition studies identified the natural product (+)-broussonetine W (4) as a selective and potent inhibitor of beta-galactosidase (IC50 = 0.03 MUM), while its enantiomer was a selective and potent inhibitor of alpha-glucosidase (IC50 = 0.047 MUM). It was found that the configuration of the polyhydroxylated pyrrolidine ring played a key role on their glycosidase inhibitory activities. The length of side chain and alpha,beta unsaturated ketone functional group also exhibited some effect on their glycosidase inhibition. PMID- 27184091 TI - Transfer-Printed PEDOT:PSS Electrodes Using Mild Acids for High Conductivity and Improved Stability with Application to Flexible Organic Solar Cells. AB - Highly conductive, flexible, and transparent electrodes (FTEs) of PEDOT: PSS films on plastic substrates have been achieved using strong acid treatments. However, it is rare to realize a performance attenuation of PEDOT: PSS FTEs on plastic substrates and flexible optoelectronic devices because of strong acid residues in the PEDOT: PSS matrix. Herein, we develop a feasible transfer printing technique using mild acids. Because of a mild and weak property of these acids and less acid residues in PEDOT: PSS matrix, the transferred PEDOT: PSS FTEs exhibited a significant enhancement in stability, conductivity (3500 S cm( 1)), transparency, and mechanical flexibility on plastic substrates. Flexible organic solar cells with the FTEs also showed a remarkable enhancement in power conversion efficiency and stability in the ambient atmosphere. It is expected that the novel transfer-printing technique for making PEDOT: PSS FTEs is also useful in many other types of flexible optoelectronic devices. PMID- 27184092 TI - Electronic cigarette exposure triggers neutrophil inflammatory responses. AB - BACKGROUND: The use of electronic cigarettes (e-cigs) is increasing and there is widespread perception that e-cigs are safe. E-cigs contain harmful chemicals; more research is needed to evaluate the safety of e-cig use. Our aim was to investigate the effects of e-cigs on the inflammatory response of human neutrophils. METHODS: Neutrophils were exposed to e-cig vapour extract (ECVE) and the expression of CD11b and CD66b was measured by flow cytometry and MMP-9 and CXCL8 by ELISA. We also measured the activity of neutrophil elastase (NE) and MMP 9, along with the activation of inflammatory signalling pathways. Finally we analysed the biochemical composition of ECVE by ultra-high performance liquid chromatography mass spectrometry. RESULTS: ECVE caused an increase in the expression of CD11b and CD66b, and increased the release of MMP-9 and CXCL8. Furthermore, there was an increase in NE and MMP-9 activity and an increase in p38 MAPK activation. We also identified several harmful chemicals in ECVE, including known carcinogens. CONCLUSIONS: ECVE causes a pro-inflammatory response from human neutrophils. This raises concerns over the safety of e-cig use. PMID- 27184093 TI - Impact of a bronchial genomic classifier on clinical decision making in patients undergoing diagnostic evaluation for lung cancer. AB - BACKGROUND: Bronchoscopy is frequently used for the evaluation of suspicious pulmonary lesions found on computed tomography, but its sensitivity for detecting lung cancer is limited. Recently, a bronchial genomic classifier was validated to improve the sensitivity of bronchoscopy for lung cancer detection, demonstrating a high sensitivity and negative predictive value among patients at intermediate risk (10-60 %) for lung cancer with an inconclusive bronchoscopy. Our objective for this study was to determine if a negative genomic classifier result that down classifies a patient from intermediate risk to low risk (<10 %) for lung cancer would reduce the rate that physicians recommend more invasive testing among patients with an inconclusive bronchoscopy. METHODS: We conducted a randomized, prospective, decision impact survey study assessing pulmonologist recommendations in patients undergoing workup for lung cancer who had an inconclusive bronchoscopy. Cases with an intermediate pretest risk for lung cancer were selected from the AEGIS trials and presented in a randomized fashion to pulmonologists either with or without the patient's bronchial genomic classifier result to determine how the classifier results impacted physician decisions. RESULTS: Two hundred two physicians provided 1523 case evaluations on 36 patients. Invasive procedure recommendations were reduced from 57 % without the classifier result to 18 % with a negative (low risk) classifier result (p < 0.001). Invasive procedure recommendations increased from 50 to 65 % with a positive (intermediate risk) classifier result (p < 0.001). When stratifying by ultimate disease diagnosis, there was an overall reduction in invasive procedure recommendations in patients with benign disease when classifier results were reported (54 to 41 %, p < 0.001). For patients ultimately diagnosed with malignant disease, there was an overall increase in invasive procedure recommendations when the classifier results were reported (50 to 64 %, p = 0.003). CONCLUSIONS: Our findings suggest that a negative (low risk) bronchial genomic classifier result reduces invasive procedure recommendations following an inconclusive bronchoscopy and that the classifier overall reduces invasive procedure recommendations among patients ultimately diagnosed with benign disease. These results support the potential clinical utility of the classifier to improve management of patients undergoing bronchoscopy for suspect lung cancer by reducing additional invasive procedures in the setting of benign disease. PMID- 27184094 TI - A smart upconversion-based light-triggered polymer for synergetic chemo photodynamic therapy and dual-modal MR/UCL imaging. AB - We have developed a novel nanocomposite to achieve effective therapy and live surveillance of tumor tissue. In this study, fullerene (C60) with iron oxide (Fe3O4) nanoparticles and upconversion nanophosphors (UCNPs) was loaded into N succinyl-N'-4-(2-nitrobenzyloxy)-succinyl-chitosan micelles (SNSC) with good biocompatibility. In addition, hydrophobic anticancer drug docetaxel (DTX) was also loaded into the nanocomposites. The experiments conducted in vitro and in vivo demonstrated that C60/Fe3O4-UCNPs@DTX@SNSC can act synergistically to kill tumor cells by releasing chemotherapy drugs at specific target site as well as generating reactive oxygen using 980nm. In addition, it can also be used for non invasive deep magnetic resonance and upconversion fluorescence dual-mode imaging. The results indicated that this system provided an efficient method to surmount the drawback of UV or visible light-responsive polymeric systems for controlled drug release and generated reactive oxygen in deep tissues and ultimately realized the integration of dual-modal imaging and treatment. PMID- 27184096 TI - Multifunctional BSA-Au nanostars for photoacoustic imaging and X-ray computed tomography. AB - We report the synthesis and characterization of bovine serum albumin-capped Au nanostars (BSA-AuNSs) for dual-modal computed tomography (CT)/photoacoustic (PA) imaging application. The BSA-AuNSs have an average size of 85nm, and a surface plasmon resonance (SPR) peak at approximately 770nm. They have excellent biocompatibility, good X-ray attenuation, and great PA contrast enhancement properties. When injected intravenously, liver signal markedly increases in both CT and PA modalities. The in vivo biodistribution studies and pathology results showed that the BSA-AuNSs were mainly excreted through the liver and intestines with no obvious biotoxicity. These results indicate that BSA-AuNSs have high potential to be used as dual-modal CT/PA imaging contrast agents or further used to develop targeted probes. This preliminary study suggests that PA tomography may be used to non-invasively trace the kinetics and biodistribution of the nanoparticles. PMID- 27184095 TI - Polymer nanocomposites enhance S-nitrosoglutathione intestinal absorption and promote the formation of releasable nitric oxide stores in rat aorta. AB - Alginate/chitosan nanocomposite particles (GSNO-acNCPs), i.e. S nitrosoglutathione (GSNO) loaded polymeric nanoparticles incorporated into an alginate and chitosan matrix, were developed to increase the effective GSNO loading capacity, a nitric oxide (NO) donor, and to sustain its release from the intestine following oral administration. Compared with free GSNO and GSNO loaded nanoparticles, GSNO-acNCPs promoted 2.7-fold GSNO permeation through a model of intestinal barrier (Caco-2 cells). After oral administration to Wistar rats, GSNO acNCPs promoted NO storage into the aorta during at least 17h, as highlighted by (i) a long-lasting hyporeactivity to phenylephrine (decrease in maximum vasoconstrictive effect of aortic rings) and (ii) N-acetylcysteine (a thiol which can displace NO from tissues)-induced vasodilation of aorxxtic rings preconstricted with phenylephrine. In conclusion, GSNO-acNCPs enhance GSNO intestinal absorption and promote the formation of releasable NO stores into the rat aorta. GSNO-acNCPs are promising carriers for chronic oral application devoted to the treatment of cardiovascular diseases. PMID- 27184097 TI - Nanostructured glycopolymer augmented liposomes to elucidate carbohydrate mediated targeting. AB - Carbohydrate receptors on alveolar macrophages are attractive targets for receptor-mediated delivery of nanostructured therapeutics. In this study, we employed reversible addition fragmentation chain transfer polymerization to synthesize neoglycopolymers, consisting of mannose- and galactose methacrylate based monomers copolymerized with cholesterol methacrylate for use in functional liposome studies. Glycopolymer-functional liposomes were employed to elucidate macrophage mannose receptor (CD206) and macrophage galactose-type lectin (CD301) targeting in both primary macrophage and immortal macrophage cell lines. Expression of CD206 and CD301 was observed to vary significantly between cell lines (murine alveolar macrophage, murine bone marrow-derived macrophage, RAW264.7, and MH-S), which has significant implications in in vitro targeting and uptake studies. Synthetic glycopolymers and glycopolymer augmented liposomes demonstrated specific receptor-mediated uptake in a manner dependent on carbohydrate receptor expression. These results establish a platform capable of probing endogenous carbohydrate receptor-mediated targeting via glycofunctional nanomaterials. PMID- 27184098 TI - Electrohydrodynamic encapsulation of cisplatin in poly (lactic-co-glycolic acid) nanoparticles for controlled drug delivery. AB - Targeted delivery of potent, toxic chemotherapy drugs, such as cisplatin, is a significant area of research in cancer treatment. In this study, cisplatin was successfully encapsulated with high efficiency (>70%) in poly (lactic-co-glycolic acid) polymeric nanoparticles by using electrohydrodynamic atomization (EHDA) where applied voltage and solution flow rate as well as the concentration of cisplatin and polymer were varied to control the size of the particles. Thus, nanoparticles were produced with three different drug:polymer ratios (2.5, 5 and 10wt% cisplatin). It was shown that smaller nanoparticles were produced with 10wt% cisplatin. Furthermore, these demonstrated the best sustained release (smallest burst release). By fitting the experimental data with various kinetic models it was concluded that the release is dependent upon the particle morphology and the drug concentration. Thus, these particles have significant potential for cisplatin delivery with controlled dosage and release period that are crucial chemotherapy parameters. PMID- 27184099 TI - Systemic Review of Anatomic Single- Versus Double-Bundle Anterior Cruciate Ligament Reconstruction: Does Femoral Tunnel Drilling Technique Matter? AB - PURPOSE: To provide an up-to-date assessment of the difference between anatomic double-bundle anterior cruciate ligament (ACL) reconstruction (DB-ACLR) and anatomic single-bundle ACL reconstruction (SB-ACLR). We hypothesized that anatomic SB-ACLR using independent femoral drilling technique would be able to achieve kinematic stability as with anatomic DB-ACLR. METHODS: A comprehensive Internet search was performed to identify all therapeutic trials of anatomic DB ACLR versus anatomic SB-ACLR. Only clinical studies of Level I and II evidence were included. The comparative outcomes were instrument-measured anterior laxity, Lachman test, pivot shift, clinical outcomes including objective/subjective International Knee Documentation Committee (IKDC) score, Lysholm score, Tegner activity scale and complication rates of extension/flexion deficits, graft failure, and early osteoarthritis. Subgroup analyses were performed for femoral tunnel drilling techniques including independent drilling and transtibial (TT) drilling. RESULTS: Twenty-two clinical trials of 2,261 anatomically ACL reconstructed patients were included in the meta-analysis. Via TT drilling technique, anatomic DB-ACLR led to improved instrument-measured anterior laxity with a standard mean difference (SMD) of -0.42 (95% confidence interval [CI] = 0.81 to -0.02), less rotational instability measured by pivot shift (SMD = 2.76, 95% CI = 1.24 to 6.16), and higher objective IKDC score with odds ratio (OR) of 2.28 (95% CI = 1.19 to 4.36). Via independent drilling technique, anatomic DB ACLR yielded better pivot shift (SMD = 2.04, 95% CI = 1.36 to 3.05). Anatomic DB ACLR also revealed statistical significance in subjective IKDC score compared with anatomic SB-ACLR (SMD = 0.27, 95% CI = 0.05 to 0.49). CONCLUSIONS: Anatomic DB-ACLR showed better anterior and rotational stability and higher objective IKDC score than anatomic SB-ACLR via TT drilling technique. Via independent drilling technique, however, anatomic DB-ACLR only showed superiority of rotational stability. All clinical function outcomes except subjective IKDC score were not significantly different between anatomic DB-ACLR and SB-ACLR. LEVEL OF EVIDENCE: Level II, meta-analysis of Level I and II studies. PMID- 27184100 TI - Repair of Meniscal Ramp Lesions Through a Posteromedial Portal During Anterior Cruciate Ligament Reconstruction: Outcome Study With a Minimum 2-Year Follow-up. AB - PURPOSE: To evaluate the results of arthroscopic all-inside suture repair of medial meniscal ramp lesions through a posteromedial portal during anterior cruciate ligament (ACL) reconstruction. METHODS: All patients who underwent a suture of the posterior segment of the medial meniscus using a suture hook device through a posteromedial portal during ACL reconstruction with minimum 2 year follow-up were included in the study. Repair was performed for longitudinal tears within the rim of less than 3 mm (capsulomeniscal junction or red-red zone) or 3 to 5 mm (red-white zone) of an unstable torn meniscus. Patients were assessed pre and postoperatively with IKDC score and Tegner activity scale. Instrumented knee testing was performed with the Rolimeter arthrometer. Complications including reoperation for failed meniscal repair were also recorded. RESULTS: One hundred thirty-two patients met the inclusion criteria. The mean follow-up time was 27 months (range, 24 to 29 months). The average subjective IKDC rose from 63.8 +/- 13.5 (range, 27 to 92) preoperatively to 85.7 +/- 12 (range, 43 to 100) at last follow-up (P < .0001). The Rolimeter test decreased from a side-to-side difference in anterior knee laxity of 7 mm (range, 5 to 14 mm) to a mean value of 0.4 mm (range, -3 to 5 mm) at last follow-up (P < .0001). The Tegner activity scale at the last follow-up (6.9 +/- 1.72) was slightly lower than that before surgery (7.2 +/- 1.92; P = .0017). Nine patients (6.8%) had failure of the meniscal repair. In 5 cases, recurrent tears were related to a newly formed tear located anterior to the initial tear. CONCLUSIONS: Our results show that arthroscopic meniscal repair of ramp lesions during ACL reconstruction through a posteromedial portal provided a high rate of meniscus healing at the level of the tear and appeared to be safe and effective in this group of patients. LEVEL OF EVIDENCE: Level IV, therapeutic study, case series (no control group). PMID- 27184101 TI - Characterization of tableting properties measured with a multi-functional compaction instrument for several pharmaceutical excipients and actual tablet formulations. AB - Before designing tablet formulations, it is important to understand the "Tableting Properties" of excipients and API (active pharmaceutical ingredient) powders. Those properties refer to "Compressibility", "Compactability" and "Manufacturability", which are difficult to evaluate quantitatively. In this study, we aimed to evaluate the "Tableting Properties" by using a benchtop single punch tablet press, developed recently to measure these parameters using a single device. In order to facilitate understanding of the results visually, we proposed a new plot, where the X-axis showed the tensile fracture stress and the Y-axis showed the ejection stress. This plot, which is composed of four regions, shows the combination of "Compactability" and "Manufacturability". We confirmed the ability of this device to evaluate the characteristics of typical pharmaceutical additives as a value of "Tableting Properties". Losartan potassium was used as an API, and Dilactose R and MCC as an excipient with good "Tableting Properties". The ejection stresses of losartan potassium and Dilactose R were very high. An increase in magnesium stearate shifted the point along the Y-axis in this plot, and it meant an improvement in "Manufacturability". It was confirmed that the device and plot are useful in designing formulations efficiently using a small amount of sample powders. PMID- 27184102 TI - Dealing with nanosafety around the globe-Regulation vs. innovation. AB - In recent years, nanotechnology has become increasingly important for global industries. Today, many nanomaterials are used as ingredients in cosmetics, food products, medical devices and pharmaceuticals. In some cases they exert unexpected risks and potentially pose a threat to human health and the environment. Regulatory authorities all over the world carefully observe recent developments in this area, striving to find a balance between consumer safety and the interests of the industry. In the following, the current legislation in the United States of America, the European Union, Asia and Brazil will be presented. Further, the requirements defined by these different authorities and methodology to investigate relevant characteristics of nanomaterials will be discussed. PMID- 27184103 TI - Discovery of a novel covalent non-beta-lactam inhibitor of the metallo-beta lactamase NDM-1. AB - The inhibition of metallo-beta-lactamases (MBL) can prevent the hydrolysis of beta-lactam antibiotics and hence is a promising strategy for the treatment of antibiotic resistant infections. In this study, we present a novel reversible covalent inhibitor of the clinically relevant MBL New Delhi metallo-beta lactamase 1 (NDM-1). Electrospray ionization-mass spectrometry (ESI-MS) and single site directed mutagenesis were used to show that the inhibitor forms a covalent bond with Lys224 in the active site of NDM-1. The inhibitor was further characterized using an enzyme inhibition assay, a surface plasmon resonance (SPR) based biosensor assay and covalent docking. The determined inhibition constant (KI(*)) was 580nM and the inhibition constant for the initial complex (KI) was 76MUM. To our knowledge, this inhibitor is the first example for a reversible covalent non-beta-lactam inhibitor targeting NDM-1 and a promising starting point for the design of potent covalent inhibitors. PMID- 27184104 TI - Risk factors of systemic inflammation response syndrome after endoscopic combined intrarenal surgery in the modified Valdivia position. AB - OBJECTIVE: To identify risk factors of developing systemic inflammation response syndrome after endoscopic combined intrarenal surgery in the modified Valdivia position for renal stone treatment. METHODS: We retrospectively analyzed 370 consecutive patients who underwent endoscopic combined intrarenal surgery procedures in the modified Valdivia position to treat renal stones. Antibiotic therapy based on preoperative urine cultures was administered to all patients from induction of anesthesia until at least postoperative day 3. Postoperative systemic inflammation response syndrome was diagnosed if the patient met two or more systemic inflammation response syndrome criteria. A multivariate logistic regression model with backward selection was used to evaluate the relationships between the incidence of systemic inflammation response syndrome after endoscopic combined intrarenal surgery and other clinical factors. RESULTS: Of the 370 patients, 61 patients (16.5%) were diagnosed with systemic inflammation response syndrome after endoscopic combined intrarenal surgery. Significant differences were found between the non-systemic inflammation response syndrome and systemic inflammation response syndrome groups with regard to female sex (29.8% vs 44.3%, P = 0.027), history of febrile urinary tract infection (16.5% vs 32.8%, P = 0.015) and number of involved calyces (2.68 vs 4.1, P < 0.001). Multivariate analysis found three independent predictors of postoperative systemic inflammation response syndrome: the number of involved calyces (P = 0.017), stone surface area (P = 0.021) and history of febrile urinary tract infection (P = 0.005). CONCLUSIONS: The number of involved calyces larger than four, stone surface area >500 mm(2) and a history of febrile urinary tract infection independently predicted the development of systemic inflammation response syndrome after endoscopic combined intrarenal surgery. This is the first study to identify the independent predictors of systemic inflammation response syndrome after endoscopic combined intrarenal surgery in the modified Valdivia position. PMID- 27184105 TI - The role of protein intrinsic disorder in major psychiatric disorders. AB - Although new candidate genes for Autism Spectrum Disorder (ASD), Schizophrenia (SCZ), Attention-Deficit/Hyperactivity Disorder (ADHD), and Bipolar Disorder (BD) emerged from genome-wide association studies (GWAS), their underlying molecular mechanisms remain poorly understood. Evidences of the involvement of intrinsically disordered proteins in diseases have grown in the last decade. These proteins lack tridimensional structure under physiological conditions and are involved in important cellular functions such as signaling, recognition and regulation. The aim of the present study was to identify the role and abundance of intrinsically disordered proteins in a set of psychiatric diseases and to test whether diseases are different regarding protein intrinsic disorder. Our hypothesis is that differences across psychiatric illnesses phenotypes and symptoms may arise from differences in intrinsic protein disorder content and properties of each group. A bioinformatics prediction of intrinsic disorder was performed in proteins retrieved based on top findings from GWAS, Copy Number Variation and candidate gene investigations for each disease. This approach revealed that about 80% of studied proteins presented long stretches of disorder. This amount was significantly higher than that observed in general eukaryotic proteins, and those involved in cardiovascular diseases. These results suggest that proteins with intrinsic disorder are a common feature of neurodevelopment and synaptic transmission processes which are potentially involved in the etiology of psychiatric diseases. Moreover, we identified differences between ADHD and ASD when the binary prediction of structure and putative binding sites were compared. These differences may be related to variation in symptom complexity between both diseases. (c) 2016 Wiley Periodicals, Inc. PMID- 27184106 TI - Magnetic and fluorescent carbon-based nanohybrids for multi-modal imaging and magnetic field/NIR light responsive drug carriers. AB - Carbon nanomaterials have gained significant momentum as promising candidate materials for biomedical applications due to their unique structure and properties. After functionalization with magnetic and fluorescent components, the resultant carbon-based nanohybrids can serve not only as magnetic resonance and fluorescence imaging contrast agents, but also as photothermally/magneto thermally responsive drug carriers for combined photothermo/chemotherapy. This mini-review summarizes the latest developments and applications and addresses the future perspectives of carbon-based magnetic and fluorescent nanohybrids in the biomedical field. PMID- 27184107 TI - High Efficiency Pb-In Binary Metal Perovskite Solar Cells. AB - Mixed Pb-In perovskite solar cells are fabricated by using lead(II) chloride and indium(III) chloride with methylammonium iodide. A maximum power conversion efficiency as high as 17.55% is achieved owing to the high quality of perovskites with multiple ordered crystal orientations. PMID- 27184108 TI - The protonation state of histidine 111 regulates the aggregation of the evolutionary most conserved region of the human prion protein. AB - In a group of neurodegenerative diseases, collectively termed transmissible spongiform encephalopathies, the prion protein aggregates into beta-sheet rich amyloid-like deposits. Because amyloid structure has been connected to different prion strains and cellular toxicity, it is important to obtain insight into the structural properties of prion fibrils. Using a combination of solution NMR spectroscopy, thioflavin-T fluorescence and electron microscopy we here show that within amyloid fibrils of a peptide containing residues 108-143 of the human prion protein [humPrP (108-143)]-the evolutionary most conserved part of the prion protein - residue H111 and S135 are in close spatial proximity and their interaction is critical for fibrillization. We further show that residues H111 and H140 share the same microenvironment in the unfolded, monomeric state of the peptide, but not in the fibrillar form. While protonation of H140 has little influence on fibrillization of humPrP (108-143), a positive charge at position 111 blocks the conformational change, which is necessary for amyloid formation of humPrP (108-143). Our study thus highlights the importance of protonation of histidine residues for protein aggregation and suggests point mutations to probe the structure of infectious prion particles. PMID- 27184109 TI - Characteristics of Mitochondrial Transformation into Human Cells. AB - Mitochondria can be incorporated into mammalian cells by simple co-incubation of isolated mitochondria with cells, without the need of transfection reagents or any other type of intervention. This phenomenon was termed mitochondrial transformation, and although it was discovered in 1982, currently little is known regarding its mechanism(s). Here we demonstrate that mitochondria can be transformed into recipient cells very quickly, and co-localize with endogenous mitochondria. The isolated mitochondria interact directly with cells, which engulf the mitochondria with cellular extensions in a way, which may suggest the involvement of macropinocytosis or macropinocytosis-like mechanisms in mitochondrial transformation. Indeed, macropinocytosis inhibitors but not clathrin-mediated endocytosis inhibition-treatments, blocks mitochondria transformation. The integrity of the mitochondrial outer membrane and its proteins is essential for the transformation of the mitochondria into cells; cells can distinguish mitochondria from similar particles and transform only intact mitochondria. Mitochondrial transformation is blocked in the presence of the heparan sulfate molecules pentosan polysulfate and heparin, which indicate crucial involvement of cellular heparan sulfate proteoglycans in the mitochondrial transformation process. PMID- 27184110 TI - Effect of G gene-deleted recombinant viral hemorrhagic septicemia virus (rVHSV DeltaG) on the replication of wild type VHSV in a fish cell line and in olive flounder (Paralichthys olivaceus). AB - In an earlier study, we generated a replicon viral hemorrhagic septicemia virus (VHSV) particle that was lacking the G gene in the genome (rVHSV-DeltaG), and proved the potential of it as a protective vaccine through the immunization of olive flounder (Paralichthys olivaceus) fingerlings. Safety is the most important preconsideration for the development of recombinant live vaccines, and a major concern of propagation-incompetent viral particles would be the possible harmful effect to hosts through the interaction with wild-type viruses. Thus, in the present study, we analyzed the replication of rVHSV-DeltaG in the presence of wild-type VHSV and the effect of rVHSV-DeltaG on the replication of wild-type VHSV in Epithelioma papulosum cyprini (EPC) cells and in olive flounder fingerlings. The replication of wild-type VHSV in EPC cells was severely suppressed when the MOI of rVHSV-DeltaG was 0.1 or 0.01, on the other hand, the titers of rVHSV-DeltaG were not increased and stayed in a relatively constant according to time lapse. Furthermore, the replication of other novirhabdoviruses, IHNV and HIRRV, was also inhibited by co-infection with high titers of rVHSV DeltaG. There were no big differences in mortalities between groups infected with wild-type VHSV plus rVHSV-DeltaG and groups infected with wild-type VHSV alone, when the challenged wild-type VHSV was more than 10(2) PFU/fish. However, a group of fish infected with 10 PFU/fish of wild-type VHSV plus rVHSV-DeltaG showed significantly lower and slowly progressing cumulative mortality than a group of fish infected with 10 PFU/fish of wild-type VHSV alone. This result suggests that rVHSV-DeltaG has an ability to attenuate the disease progression caused by wild type VHSV when co-infected with relatively low titers of wild-type VHSV. These results indicate that the propagation-incompetent rVHSV-DeltaG would not worsen but attenuate the progression of a disease caused by wild-type VHSV infection. Therefore, rVHSV-DeltaG-based vaccines can provide a safe and effective way to control VHSV. PMID- 27184111 TI - Protective effects of the prebiotic on the immunological indicators of rainbow trout (Oncorhynchus mykiss) infected with Aeromonas hydrophila. AB - The aim of this study was to investigate the protective effects of dietary administration of commercial prebiotic, Immunogen, on immunological indicators, enzymatic responses and stress tolerance in juvenile (81.65 +/- 1.49) rainbow trout (Oncorhynchus mykiss) following Aeromonas hydrophila infection. The first group of fish was fed with the diet containing 2 g kg(-1) Immunogen whilst the control group received the diet free of Immunogen. There were three replicates per group. After 6 weeks feeding, the control group were divided into two treatments injected with saline buffer (control), and 1.5 * 10(8) CFU A. hydrophila respectively. The fish fed with the Immunogen supplemented diet were also injected with 1.5 * 10(8) CFU A. hydrophila. Our results revealed that dietary Immunogen increased the level of white blood cell (WBC) and percentage of lymphocyte (P < 0.05), however, the level of red blood cell (RBC), Hematocrit (Hct), hemoglobin (Hb) and percent of monocyte decreased in Untreated-Challenged group but unaffected in the group fed with Immunogen (P < 0.05). The level of lysozyme, alternative complement, antiprotease activity, total protein, albumin and globulin decreased in Untreated- Challenged group compared to control group. However, there was an increase in the level of lysozyme, alternative complement, antiprotease activity, bactericidal activity, in the Treated- Challenged group compared to other groups (P < 0.05). Serum alkali phosphatase (ALT) and aspartate aminotransferase, significantly increased fallowing challenge with A. hydrophila but in the Treated-Challenged group, there was no significant difference compared to the control group (P < 0.05). Lactate dehydrogenase (LDH) level was not different between groups (P > 0.05). Serum cortisol and glucose levels were higher in the challenge group, but these levels were lower in fish under challenge that were fed Immunogen-supplemented diet in contrast to the group fed control diet. The stress responses affected by A. hydrophila challenge (P < 0.05). Serum sodium, potassium and calcium concentration decreased by A. hydrophila exposure (P < 0.05), and Immunogen showed protection effect against this change. PMID- 27184113 TI - Management of chemotherapy-induced nausea and vomiting in patients receiving multiple-day highly or moderately emetogenic chemotherapy: role of transdermal granisetron. AB - Granisetron transdermal delivery system (GTDS) is the first 5-HT3 drug to be transdermally delivered and represents a convenient alternative to oral and intravenous antiemetics for the treatment of chemotherapy-induced nausea and vomiting. GTDS is effective and well tolerated in patients receiving multiple-day moderate-to-highly emetogenic chemotherapy. In this setting noninferiority studies showed similar efficacy when GTDS was compared with intravenous and oral granisetron and intravenous palonosetron. GTDS has shown good cardiovascular safety; however, special caution is needed in patients at risk for developing excessive QTc interval prolongation and arrhythmias. So far, GTDS has been investigated for intravenous prevention in comparison with granisetron and palonosetron; however, further prospects open the route to future clinical investigations. PMID- 27184112 TI - Prognostic Significance of TERT Promoter Mutations in Papillary Thyroid Carcinomas in a BRAF(V600E) Mutation-Prevalent Population. AB - BACKGROUND: The role of telomerase reverse transcriptase (TERT) promoter mutations in differentiated thyroid cancer has been well established. These mutations have a significantly higher prevalence in aggressive thyroid tumors, including widely invasive oncocytic carcinomas, poorly differentiated carcinomas, and anaplastic thyroid carcinomas. Interestingly, in some studies, TERT mutations were found to be more common in tumors with a BRAF(V600E) mutation. However, mutational analysis of TERT promoter mutations in thyroid tumors has not been previously performed for patients in Korea, where the BRAF(V600E) mutation in papillary thyroid carcinoma (PTC) is particularly prevalent. This study analyzed TERT promoter mutations in various thyroid tumors and examined their relationship with clinicopathologic factors and the BRAF(V600E) mutation in PTC cases. METHODS: Using 242 preoperative fine-needle aspiration biopsy specimens (including 207 PTCs) with confirmed histopathological diagnosis of the biopsied thyroid nodules, the TERT promoter status (C228T and C250T) was analyzed, and the relationship with clinicopathologic factors and the BRAF(V600E) mutation in PTC cases was examined. RESULTS: Of 242 patients, 14.5% (30/207), 26.7% (4/15), 50% (1/2), and 60% (2/5) of PTCs, follicular thyroid carcinomas, poorly differentiated carcinomas, and anaplastic thyroid carcinomas harbored a TERT(C228T) mutation, respectively. The TERT(C228T) mutation was associated with recurrence (p = 0.03). However, no association with other clinicopathologic factors in PTC was found. Coexistence of TERT(C228T) and BRAF(V600E) mutations was found in 13.0% of PTCs and was significantly associated with older age and advanced stage compared with the group negative for either mutation. The TERT(C228T) mutation status was an independent prognostic factor for recurrence free survival (hazard ratio = 3.08 [confidence interval 1.042-9.079]; p = 0.042) in patients with PTC in multivariate analysis. CONCLUSIONS: Identification of TERT promoter mutations in preoperative fine-needle aspiration biopsy specimens may help in better characterizing the prognosis and triaging thyroid cancer patients for appropriate treatment. PMID- 27184114 TI - Breath concentration of acetic acid vapour is elevated in patients with cystic fibrosis. AB - A study has been carried out of the volatile organic compounds present in the exhaled breath of 58 cystic fibrosis (CF) patients. An important observation is that the acetic acid vapour concentration measured by selected ion flow tube mass spectrometry (SIFT-MS) is significantly elevated in the exhaled breath of CF patients, independent of the Pseudomonas aeruginosa (PA) infection status (PA infected median 170 ppbv; PA-negative median 182 ppbv), compared to that of healthy controls (median 48 ppbv). The cause for this may be decreased pH of the mucus lining the CF airways. Thus, we speculate that non-invasive measurement of breath acetic acid concentration could serve as an indicator of the acidity of the CF airways mucosa. PMID- 27184115 TI - Microstructure and mechanical properties of sheep horn. AB - The sheep horn presents outstanding mechanical properties of impact resistance and energy absorption, which suits the need of the vehicle bumper design, but the mechanism behind this phenomenon is less investigated. The microstructure and mechanical properties of the sheep horn of Small Tailed Han Sheep (Ovis aries) living in northeast China were investigated in this article. The effect of sampling position and orientation of the sheep horn sheath on mechanical properties were researched by tensile and compression tests. Meanwhile, the surface morphology and microstructure of the sheep horn were observed using scanning electron microscopy (SEM). The formation mechanism of the mechanical properties of the sheep horn was investigated by biological coupling analysis. The analytical results indicated that the outstanding mechanical properties of the sheep horn are determined by configuration, structure, surface morphology and material coupling elements. These biological coupling elements make the sheep horn possess super characteristics of crashworthiness and energy absorption through the internal coupling mechanism. We suppose that these findings would make a difference in vehicle bumper design. Microsc. Res. Tech. 79:664-674, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27184116 TI - The ICMJE editors' proposal on sharing individual data collected in clinical trials: Comments. PMID- 27184118 TI - Defective excitation-contraction coupling is partially responsible for impaired contractility in hindlimb muscles of Stac3 knockout mice. AB - The Stac3 gene is exclusively expressed in skeletal muscle, and Stac3 knockout is perinatal lethal in mice. Previous data from Stac3-deleted diaphragms indicated that Stac3-deleted skeletal muscle could not contract because of defective excitation-contraction (EC) coupling. In this study, we determined the contractility of Stac3-deleted hindlimb muscle. In response to frequent electrostimulation, Stac3-deleted hindlimb muscle contracted but the maximal tension generated was only 20% of that in control (wild type or heterozygous) muscle (P < 0.05). In response to high [K(+)], caffeine, and 4-chloro-m-cresol (4 CMC), the maximal tensions generated in Stac3-deleted muscle were 29% (P < 0.05), 58% (P = 0.08), and 55% (P < 0.05) of those in control muscle, respectively. In response to 4-CMC or caffeine, over 90% of myotubes formed from control myoblasts contracted, but only 60% of myotubes formed from Stac3-deleted myoblasts contracted (P = 0.05). However, in response to 4-CMC or caffeine, similar increases in intracellular calcium concentration were observed in Stac3-deleted and control myotubes. Gene expression and histological analyses revealed that Stac3-deleted hindlimb muscle contained more slow type-like fibers than control muscle. These data together confirm a critical role of STAC3 in EC coupling but also suggest that STAC3 may have additional functions in skeletal muscle, at least in the hindlimb muscle. PMID- 27184117 TI - Anatomy of RISC: how do small RNAs and chaperones activate Argonaute proteins? AB - RNA silencing is a eukaryote-specific phenomenon in which microRNAs and small interfering RNAs degrade messenger RNAs containing a complementary sequence. To this end, these small RNAs need to be loaded onto an Argonaute protein (AGO protein) to form the effector complex referred to as RNA-induced silencing complex (RISC). RISC assembly undergoes multiple and sequential steps with the aid of Hsc70/Hsp90 chaperone machinery. The molecular mechanisms for this assembly process remain unclear, despite their significance for the development of gene silencing techniques and RNA interference-based therapeutics. This review dissects the currently available structures of AGO proteins and proposes models and hypotheses for RISC assembly, covering the conformation of unloaded AGO proteins, the chaperone-assisted duplex loading, and the slicer-dependent and slicer-independent duplex separation. The differences in the properties of RISC between prokaryotes and eukaryotes will also be clarified. WIREs RNA 2016, 7:637 660. doi: 10.1002/wrna.1356 For further resources related to this article, please visit the WIREs website. PMID- 27184120 TI - Plasma prolactin and breast cancer risk: a meta- analysis. AB - Breast cancer is the most common cancer among women, and its incidence is on a constant rise. Previous studies suggest that higher levels of plasma prolactin are associated with escalated risk of breast cancer, however, these results are contradictory and inconclusive. PubMed and Medline were used to search and identify published observational studies that assessed the relationship between plasma prolactin levels and the risk of breast cancer. The pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a fixed-effects or random-effects model. A total of 7 studies were included in our analysis. For the highest versus lowest levels of plasma prolactin, the pooled RR (95% CI) of breast cancer were 1.16 (1.04, 1.29). In subgroup analyses, we found a positive association between plasma prolactin levels and the risk of breast cancer among the patients who were postmenopausal, ER(+)/PR(+) or in situ and invasive carcinoma. However, this positive association was not detected in the premenopausal and ER(-)/PR(-) patients. In conclusion, the present study provides evidence supporting a significantly positive association between plasma prolactin levels and the risk of breast cancer. PMID- 27184119 TI - Cognitive control and episodic memory in adolescents with autism spectrum disorders. AB - INTRODUCTION: To further investigate manifestations of episodic memory impairments in adolescents, we examined the role of encoding on recognition of stimuli in conditions designed to emphasize their item-specific versus relational characteristics in a group of 12-18 year olds with autism spectrum disorders (ASD). We also examined how strategic learning and memory processes, verbal abilities, attention, and age were associated with recognition in this group. MATERIALS AND METHOD: Twenty two high functioning adolescents with ASD (mean age=15 years; SD=1.8; range=12.2-17.9), and 26 age, gender, and IQ-matched adolescents with typical development (TYP) (mean age=14.7 years; SD=1.9; range=12.3-17.8) completed the Relational and Item-Specific Encoding task (RiSE), the California Verbal Learning Test-Children's Version (CVLT-C), the Wechsler Abbreviated Scales of Intelligence, and the Connors' Parent Rating Scale-Revised. Univariate statistical analyses were performed. RESULTS: The ASD group showed poorer performance on strategic memory assessed by the CVLT-C. Surprisingly, on the RiSE, ASD showed poorer discriminability for objects encoded in item-specific versus relational encoding conditions and were more impaired in familiarity (after relational encoding) than in recollection. ASD also did not show the hypothesized association between item and associative recognition and CVLT-C performance found in TYP. Instead, in the ASD group recognition was associated with increased age. CONCLUSIONS: Findings from the RiSE task demonstrated that adolescents with ASD do not always exhibit impaired memory for relational information as commonly believed. Instead, memory was worse when cognitive control demands were high, when encoding focused on specific item features, and when familiarity was used to retrieve relational information. Recognition also was better in older participants. This suggests that learning and memory deficits in adolescents with ASD, may not be due primarily to failed relational binding processes in the hippocampus but, rather to disrupted strategic memory and familiarity processes associated with the prefrontal and perirhinal cortices. These findings demonstrate the importance and utility of using well-validated cognitive neuroscience tasks and of considering the ages of participants when comparing the neural underpinnings of different memory processes in both typical and atypical populations. PMID- 27184121 TI - Logic circuits composed of flexible carbon nanotube thin-film transistor and ultra-thin polymer gate dielectric. AB - Printing electronics has become increasingly prominent in the field of electronic engineering because this method is highly efficient at producing flexible, low cost and large-scale thin-film transistors. However, TFTs are typically constructed with rigid insulating layers consisting of oxides and nitrides that are brittle and require high processing temperatures, which can cause a number of problems when used in printed flexible TFTs. In this study, we address these issues and demonstrate a method of producing inkjet-printed TFTs that include an ultra-thin polymeric dielectric layer produced by initiated chemical vapor deposition (iCVD) at room temperature and highly purified 99.9% semiconducting carbon nanotubes. Our integrated approach enables the production of flexible logic circuits consisting of CNT-TFTs on a polyethersulfone (PES) substrate that have a high mobility (up to 9.76 cm(2) V(-1) sec(-)1), a low operating voltage (less than 4 V), a high current on/off ratio (3 * 10(4)), and a total device yield of 90%. Thus, it should be emphasized that this study delineates a guideline for the feasibility of producing flexible CNT-TFT logic circuits with high performance based on a low-cost and simple fabrication process. PMID- 27184122 TI - Haploinsufficiency of the 22q11.2 microdeletion gene Mrpl40 disrupts short-term synaptic plasticity and working memory through dysregulation of mitochondrial calcium. AB - Hemizygous deletion of a 1.5- to 3-megabase region on chromosome 22 causes 22q11.2 deletion syndrome (22q11DS), which constitutes one of the strongest genetic risks for schizophrenia. Mouse models of 22q11DS have abnormal short-term synaptic plasticity that contributes to working-memory deficiencies similar to those in schizophrenia. We screened mutant mice carrying hemizygous deletions of 22q11DS genes and identified haploinsufficiency of Mrpl40 (mitochondrial large ribosomal subunit protein 40) as a contributor to abnormal short-term potentiation (STP), a major form of short-term synaptic plasticity. Two-photon imaging of the genetically encoded fluorescent calcium indicator GCaMP6, expressed in presynaptic cytosol or mitochondria, showed that Mrpl40 haploinsufficiency deregulates STP via impaired calcium extrusion from the mitochondrial matrix through the mitochondrial permeability transition pore. This led to abnormally high cytosolic calcium transients in presynaptic terminals and deficient working memory but did not affect long-term spatial memory. Thus, we propose that mitochondrial calcium deregulation is a novel pathogenic mechanism of cognitive deficiencies in schizophrenia. PMID- 27184123 TI - Increased pregenual anterior cingulate glucose and lactate concentrations in major depressive disorder. AB - There is ample evidence that glucose metabolism in the pregenual anterior cingulate cortex (PACC) is increased in major depressive disorder (MDD), whereas it is still unknown whether glucose levels per se are also elevated. Elevated cerebrospinal fluid (CSF) lactate concentrations in MDD patients might indicate that increased glycolytical metabolization of glucose to lactate in astrocytes either alone or in conjunction with mitochondrial dysfunction results in an accumulation of lactate and contributes to pathophysiological mechanisms of MDD. However, until now, no study investigated in vivo PACC glucose and lactate levels in MDD. Proton magnetic resonance spectroscopy was therefore used to test the hypothesis that patients with MDD have increased PACC glucose and lactate levels. In 40 healthy and depressed participants, spectra were acquired from the PACC using a maximum echo J-resolved spectroscopy protocol. Results show significant increases of glucose and lactate in patients, which are also associated with depression severity. These findings indicate impaired brain energy metabolism in MDD with increased fraction of energy utilization via glycolysis and reduced mitochondrial oxidative clearance of lactate. Targeting these metabolic disturbances might affect the balance of metabolic pathways regulating neuronal energetics and result in an attenuation of the elevated basal activity of brain regions within the neural circuitry of depression. PMID- 27184126 TI - Regrowth in ship's ballast water tanks: Think again! AB - With the imminent ratification of the International Maritime Organisation's Ballast Water Management Convention, ship owners and operators will have to choose among a myriad of different Ballast Water Treatment Systems (BWTS) and technologies to comply with established discharge standards. However, it has come to our attention that decision-makers seem to be unaware of the problem of regrowth occurring in ballast water tanks after treatment. Furthermore, the information available on the subject in the literature is surprisingly and unfortunately very limited. Herein we summarise previous research findings that suggest that regrowth of bacteria and phytoplankton could occur 18h to 7days and 4 to 20days after treatment, respectively. By highlighting the problem of regrowth, we would like to encourage scientists and engineers to further investigate this issue and to urge ship owners and ship operators to inform themselves on the risks of regrowth associated with the implementation of different BWTS. PMID- 27184125 TI - Impact of hematogones on the long-term outcomes of single-unit cord blood transplantation for adult patients. AB - Hematogones are normal B-lymphocyte precursors identified in the regenerative state of the bone marrow following allogeneic hematopoietic stem cell transplantation (HSCT). To evaluate the impact of hematogones on long-term outcomes after single-unit cord blood transplantation (CBT), we retrospectively analyzed 134 adult patients at our institute. At the median time of 41 days (range, 20 to 77 days) after CBT, the median proportion of morphological hematogones in bone marrow was found to be 2.4% (range, 0 to 13.0%). In the patients with standard-risk, the higher proportion of morphological hematogones was associated with lower transplant-related mortality (TRM) after CBT. The proportion of hematogones did not affect the subsequent absolute lymphocyte counts in the peripheral blood and serum immunoglobulin G levels six months later after CBT. These data shows that morphological hematogones in the routine bone marrow analysis might be a practical and easily evaluable method of predicting outcomes after CBT. PMID- 27184127 TI - The lipopeptide 6-2 produced by Bacillus amyloliquefaciens anti-CA has potent activity against the biofilm-forming organisms. AB - Both the whole cells and protoplasts of Pseudomonas aeruginosa PAO1 and Bacillus cereus, two biofilm-forming bacteria, were disrupted by the lipopeptide 6-2 produced by Bacillus amyloliquefaciens anti-CA. The lipopeptide 6-2 could also effectively inhibit the formation of biofilms and disperse pre-formed biofilms. Live/dead staining of the biofilms grown in the absence or presence of the lipopeptide 6-2 showed that more dead bacterial cells in the presence of the lipopeptide than those in the absence of the lipopeptide and biofilm formation was greatly reduced by the lipopeptide 6-2. Expression of the PslC gene related to exopolysaccharides in P. aeruginosa PAO1 was also inhibited. All these results demonstrated that the lipopeptide 6-2 produced by B. amyloliquefaciens anti-CA had a high activity against biofilm-forming bacteria. The lipopeptide 6-2 also killed the larvae of Balanus amphitrite and inhibit the germination of Laminaria japonica spore and growth of protozoa, all of which were the fouling organisms in marine environments. PMID- 27184128 TI - On some physical and dynamical properties of microplastic particles in marine environment. AB - Simplified physical models and geometrical considerations reveal general physical and dynamical properties of microplastic particles (0.5-5mm) of different density, shape and size in marine environment. Windage of extremely light foamed particles, surface area and fouling rate of slightly positively buoyant microplastic spheres, films and fibres and settling velocities of negatively buoyant particles are analysed. For the Baltic Sea dimensions and under the considered idealised external conditions, (i) only one day is required for a foamed polystyrene particle to cross the sea (ca. 250km); (ii) polyethylene fibres should spend about 6-8months in the euphotic zone before sinking due to bio-fouling, whilst spherical particles can be retained on the surface up to 10 15years; (iii) for heavy microplastic particles, the time of settling through the water column in the central Gotland basin (ca. 250m) is less than 18h. Proper physical setting of the problem of microplastics transport and developing of physically-based parameterisations are seen as applications. PMID- 27184129 TI - Organochlorines and polychlorinated biphenyl environmental pollution in south coast of Rio De Janeiro state. AB - The objective of this study was to evaluate the burden of environmental pollution by Polychlorinated Biphenyls (PCBs) and Organochlorine Pesticides (OCs) in two localities of Rio de Janeiro coast, through the determination of these levels in specimens of mullets and croakers collected from May to August 2008, at Guanabara Bay (GB) and from Araujo Island (AI), at Paraty Bay. Twenty three organochlorine pollutants were detected in croakers at GB and twenty in mullets and all PCBs congeners investigated in the study were present in the two species. Ratio ?DDT/?PCB of 1.4 shows an important contribution of agricultural residues in GB and p,p'-DDE/?DDT of 0.1 demonstrates a reintroduction of DDT. Consumption of mullet may represent a risk to the health of fishermen families from GB, with average and maximum estimated daily intake of ?DDT of 9.012MUg/kg p.c. and 26,174MUg/kg p.c., representing 45% and 131% of ADI established by WHO. PMID- 27184130 TI - Bioaccumulation and retention kinetics of cesium in the Milkfish Chanos chanos from Jakarta Bay. PMID- 27184131 TI - A novel methodology for the determination of biomarker baseline levels in the marine polychaete Hediste diversicolor. AB - Identifying environmental damage due to anthropogenic activities is a focal point for scientists and policy makers like those involved in the European Water Framework Directive (WFD). Many of these approaches focus on ecological endpoints for assessing environmental perturbations, which lead to policies emphasizing mitigation rather than prevention. Biomarkers provide early-warning indicators of stress but it is necessary to distinguish their natural variations from those induced by chemical stress. The global aim of this study was to establish a baseline assessment criterion (BAC) using historical data in a reference site to define toxicity thresholds. We have developed a multiple polynomial regression model (MPR) accounting the influence of salinity, temperature and size of individual on energetic reserves (glycogen and lipids) in the marine polychaete Hediste diversicolor. The model identified a complex, orthogonal relationship between confounding factors and glycogen and a linear relationship between lipids and size of individuals. PMID- 27184132 TI - Factors controlling phosphorus release from sediments in coastal archipelago areas. AB - In coastal archipelago areas of the northern Baltic Sea, significantly higher phosphate concentrations (6.0+/-4.5MUmol/l, mean+/-SD) were measured in water samples close to the sediment surface compared with those from 1m above the seafloor (1.6+/-2.0MUmol/l). The results indicated notable phosphate release from sediments under the bottom water oxygen concentrations of up to 250MUmol/l, especially in areas that had experienced recent temporal fluctuation between oxic and hypoxic/anoxic conditions. No single factor alone was found to control the elevated PO4-P concentrations in the near-bottom water. In addition to the oxygen in the water, the contents of potentially mobile phosphorus fractions, grain size, the organic content at the sediment surface, and the water depth were all important factors controlling the internal loading of phosphorus. The complexity of this process needs to be accounted for in assessments of the internal loading of phosphorus and in potential mitigation plans. PMID- 27184133 TI - Large-for-gestational-age (LGA) neonate predicts a 2.5-fold increased odds of neonatal hypoglycaemia in women with type 1 diabetes. AB - OBJECTIVE: The objective of the study is to assess the impact of maternal glycaemic control and large-for-gestational-age (LGA) infant size on the risk of developing neonatal hypoglycaemia in offspring of women with type 1 diabetes and to determine possible predictors of neonatal hypoglycaemia and LGA. RESEARCH METHODS AND DESIGN: This retrospective cohort study evaluated pregnancies in 161 women with type 1 diabetes mellitus at a large urban centre between 2006 and 2010. Mean trimester A1c values were categorized into five groups. Multiple logistic regression analyses were used to examine predictors of neonatal hypoglycaemia and large-for-gestational-age (LGA). RESULTS: Hypoglycaemia occurred in 36.6% of neonates. There was not a linear association between trimester specific A1c and LGA. After adjusting for maternal age, body mass index (BMI), smoking and premature delivery, neonatal hypoglycaemia was not linearly associated with A1c in the first, second or third trimesters. LGA was the only significant predictor for neonatal hypoglycaemia (OR, 95% CI 2.51 [1.10, 5.70]) in logistic regression analysis that adjusted for glycaemic control, maternal age, smoking, prematurity and BMI. An elevated third trimester A1c increased the odds of LGA (1.81 [1.03, 3.18]) after adjustment for smoking, parity and maternal BMI. CONCLUSIONS: Large-for-gestational-age imparts a 2.5-fold increased odds of hypoglycaemia in neonates of women with type 1 diabetes and may be a better predictor of neonatal hypoglycaemia than maternal glycaemic control. Our data suggest that LGA neonates of women with type 1 diabetes should prompt increased surveillance for neonatal hypoglycaemia and that the presence of optimum maternal glycaemic control should not reduce this surveillance. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27184135 TI - Effects of 1, 25-Dihydroxyvitamin D3 on Experimental Autoimmune Myocarditis in Mice. AB - BACKGROUND/AIMS: Myocarditis is an important inflammatory disease of the heart which causes life-threatening conditions. 1, 25(OH)2 D3 has effects on multiple systems and diseases. The present study was aimed to investigate the effect of 1, 25(OH)2 D3 on experimental autoimmune myocarditis (EAM), and explored the underlying mechanisms involved. METHODS: EAM was induced by immunizing BALB/c mice with cardiac alpha-myosin heavy chain peptides (MyHC-alpha). 1, 25(OH)2 D3 (1,000 ng/kg once) or vehicle was administered intraperitoneally every other day during the entire experiment. On day 21, transthoracic echocardiography was performed and cardiac inflammatory infiltration was detected by hematoxylin and eosin (HE). The terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL) assay, and Western blots for the expression of protein caspase-3 and cleaved-caspase3 were used to evaluate apoptosis. Transmission electron microscopy and Western blots for the expression of protein Beclin-1, LC3B, and P62 were used to evaluate autophagy. RESULTS: The ratio of heart weight/body weight was significantly reduced in 1, 25(OH)2 D3 -treated EAM mice, compared with vehicle -treated ones. 1, 25(OH)2 D3 treatment improved cardiac function, diminished cell infiltration in cardiac, suppressed myocardial apoptosis, decreased the number of autophagosomes, and decreased the protein expression of Beclin-1, LC3-II and p62. CONCLUSIONS: The present results demonstrated that administration of 1, 25(OH)2 D3 decreased EAM severity. 1, 25(OH)2 D3 treatment may be a feasible therapeutic approach for EAM. PMID- 27184136 TI - Study on mobile phone use while driving in a sample of Iranian drivers. AB - The use of cell phone is a significant source of driver distraction. Phone use while driving can impair a number of factors critical for safe driving which can cause serious traffic safety problems. The objective of this paper was to investigate the frequency of using cell phones while driving in Iran's roads through an observational survey with a random sample of drivers, to recognize contributing factors to cell phone usage and to understand the magnitude of the problem. A total of 1794 observations were collected from 12 sites at controlled intersections, entrance and exit points of highways. The cell phone use rate among drivers (talking or texting) was estimated at 10% which is significantly higher than that in other countries such as Australia, USA and Canada. Rate of cell phone use among younger drivers (14.15%) was higher in comparison with other groups. In order to identify factors affecting cell phone use while driving, a binary logit model is estimated. Variables which significantly contribute to the rate of using cell phone were found to be the age of driver, number of passengers, presence of kids under the age of 8, time of observation, vehicle price and type of car. PMID- 27184134 TI - MYC copy gain, chromosomal instability and PI3K activation as potential markers of unfavourable outcome in trastuzumab-treated patients with metastatic breast cancer. AB - BACKGROUND: There is an unmet need for more efficient patient stratification for receiving trastuzumab in the metastatic breast cancer (mBC) setting, since only part of such patients benefit from the addition of this agent to chemotherapy. The aim of this study was to investigate the prognostic value of biomarkers including MYC and MET in mBC patients treated with trastuzumab-based regimens. METHODS: mBC patients, locally tested as HER2-positive, treated with trastuzumab and chemotherapy between 1998 and 2010 were evaluated. Paraffin tumors (n = 229) were retrospectively centrally assessed by immunohistochemistry (IHC) for HER2, ER, PgR and Ki67; fluorescence in situ hybridization (FISH) for HER2, TOP2A and centromere (CEN) 17, MYC and CEN8, MET and CEN7; qPCR for MYC, MET copy number (CN); and, for PI3K activation (PIK3CA mutations; PTEN and phospho-mTOR protein expression). Increased CEN CN was assessed based on normal cut-offs. Time to progression (TTP) and survival were evaluated from the initiation of trastuzumab as first line treatment. RESULTS: Among all tumors, 90 were HER2-negative upon central testing (ambiguous HER2) and the rest were true HER2-positive. Further, 156 patients presented with mBC upon relapse of pre-treated disease (R-mBC) and 65 were diagnosed at stage IV (de novo mBC). Concordance between FISH and qPCR on gene CN status was fair for MYC (Kappa = 0.458) and absent for MET. The presence of MYC CN gain with qPCR and the absence of PI3K activation were infrequent events (7 and 8 % of evaluable tumors, respectively), while 41 % of tumors had increased CEN CN in one or more chromosomes, indicative of chromosomal instability. The most consistent finding in the entire cohort and in the above patient subgroups with respect to outcome was the unfavourable effect of MYC CN gain, which was retained upon multivariable analysis (e.g., survival in the entire cohort, HR 6.02; 95 % CI 2.67-13.6; p < 0.001). Further unfavourable prognosticators were increased CEN CN in one chromosome in R-mBC but not in de novo mBC (multivariable interaction p = 0.048), PI3K activation in R-mBC (multivariable p = 0.004) and increased Ki67 for patient TTP. CONCLUSIONS: MYC gene copies, centromere status and PI3K activation may adversely impact trastuzumab treated mBC patient outcome and seem worthy validating in larger series. PMID- 27184137 TI - Blood Transfusion is an Independent Risk Factor for Postoperative Serious Infectious Complications After Pancreaticoduodenectomy. AB - BACKGROUND/PURPOSE: Blood transfusionhas been considered as a risk factor for postoperative infection after major surgery. However, the relationship between perioperative blood transfusion and the development of serious infections after pancreaticoduodenectomy remains controversial. The purpose of this study was to analyze risk factors associated with postoperative serious infections following pancreaticoduodenectomy. METHODS: We conducted a retrospective study of 212 patients who underwent pancreaticoduodenectomy during past 2 years and assessed the risk factors for serious infectious complications. RESULTS: Serious infections developed in 61 patients (29 %) including 47 cases of surgical site infection (SSI), 19 cases of bacteremia, and 13 cases of pneumonia. One patient died of severe septic shock. A multivariate logistic regression analysis of perioperative factors identified that pancreatic fistula (P < 0.01, OR = 9.763) and blood transfusion (P < 0.01, OR = 3.216) were significant risk factors for serious infections. After excluding 46 patients with pancreatic fistula, blood transfusion continued to be an independent risk factor for serious infections (P < 0.01, OR = 5.831). CONCLUSION: Blood transfusion was the strongest independent factor for serious infections after pancreaticoduodenectomy, which should be considered a quality indicator for the performance of pancreaticoduodenectomy. PMID- 27184138 TI - Lung function and associations with multiple dimensions of dental health: a prospective observational cross-sectional study. AB - BACKGROUND: Epidemiological data suggest an association between respiratory diseases and periodontal health. However, the link between the overall dental status and single lung function measures, within a practical clinical context, is not well studied. METHODS: Following a prospective cross-sectional design, consecutive adult patients were evaluated. Next to spirometry, anthropometric data, profession, smoking status, symptoms, self-rated exercise performance, comorbidities, allergies and medication were determined. Assessment of dental status comprised carious lesions, dental fillings, missing teeth, dentures, insufficient fillings/dentures, implants, oral mucosa diseases, calculus, decayed missed-filling-teeth (DMF-T)-index, periodontal screening-index, and orthopantomograms. RESULTS: Among 587 adult patients considered, 206 were included (119 female; median age 42.0 years; 56 % smoking history). Most patients had dental fillings (86.9 %), fix/mobile dentures (66.5 %), missing teeth (56.8 %) and calculus (84.0 %), the overall DMF-T being 15 (9; 21). Periodontitis was present in 53.9 %, an abnormal orthopanthomogram in 47.9 % of subjects. Regarding spirometric indices expressed as % predicted, dentures, missing teeth, oral mucosal diseases and a DMF-T > 15 (median) were associated with lower maximal expiratory flows at 25 % of vital capacity (MEF25) (p < 0.05 each). In adjusted logistic regression analyses, only dentures were associated with low MEF25 % predicted and with the ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC; p < 0.05 each). However, periodontitis and DMF-T were linked to age (p < 0.001) and packyears (p < 0.05) only. CONCLUSION: Within a real-life clinical setting, only the presence of dentures showed weak associations with lung function, suggesting small airways dysfunction and obstruction. Most of the associations were explained by smoking habits and age. PMID- 27184139 TI - GnRH antagonist rescue protocol combined with cabergoline versus cabergoline alone in the prevention of ovarian hyperstimulation syndrome: a randomized controlled trial. AB - BACKGROUND: The aim of this study was to compare the efficacy of antagonist rescue protocol (replacing GnRH agonist with GnRH antagonist and reducing the dose of gonadotropins) combined with cabergoline versus cabergoline alone in the prevention of ovarian hyperstimulation syndrome (OHSS) in patients pretreated with GnRH agonist long protocol who were at high risk for OHSS. METHODS: Two hundred and thirty six patients were randomized in a 1:1 ratio to the cabergoline group or the antagonist rescue combined with cabergoline group. Both groups received oral cabergoline (0.5 mg/day) for eight days beginning on the day of HCG administration. In the antagonist rescue combined with cabergoline group, when the leading follicle reached 16 mm, GnRH agonist (triptorelin) was replaced with GnRH antagonist (cetrorelix acetate) and the dose of HP-uFSH was reduced to 75 IU/day. HCG (5,000 IU/I.M) was administered when the serum estradiol level dropped below 3500 pg/ml. The study was open label and the outcome assessors (laboratory staff and the doctor who performed oocyte retrieval) were blind to treatment allocation. RESULTS: The incidence of moderate/severe OHSS was significantly lower in the antagonist rescue combined with cabergoline group [5.08 % Vs 13.56 %, P value =0.025, OR = 0.342, 95 % CI, 0.129-0.906]. Four cycles were cancelled in the cabergoline group. There were no significant differences between the groups with respect to the number of retrieved oocytes, metaphase II oocytes, high quality embryos and fertilization rate. Moreover, the implantation and pregnancy rates were comparable between both groups. CONCLUSION: GnRH antagonist rescue protocol combined with cabergoline is more effective than cabergoline alone in the prevention of OHSS. TRIAL REGISTRATION: Clinical trial.gov ( NCT02461875 ). PMID- 27184140 TI - CORR Insights(r): What are the Conditional Survival and Functional Outcomes After Surgical Treatment of 115 Patients with Sacral Chordoma? PMID- 27184141 TI - The non-genomic loss of function of tumor suppressors: an essential role in the pathogenesis of chronic myeloid leukemia chronic phase. AB - BACKGROUND: Chronic Myeloid Leukemia was always referred as a unique cancer due to the apparent independence from tumor suppressors' deletions/mutations in the early stages of the disease. However, it is now well documented that even genetically wild-type tumor suppressors can be involved in tumorigenesis, when functionally inactivated. In particular, tumor suppressors' functions can be impaired by subtle variations of protein levels, changes in cellular compartmentalization and post-transcriptional/post-translational modifications, such as phosphorylation, acetylation, ubiquitination and sumoylation. Notably, tumor suppressors inactivation offers challenging therapeutic opportunities. The reactivation of an inactive and genetically wild-type tumor suppressor could indeed promote selective apoptosis of cancer cells without affecting normal cells. MAIN BODY: Chronic Myeloid Leukemia (CML) could be considered as the paradigm for non-genomic loss of function of tumor suppressors due to the ability of BCR-ABL to directly promote functionally inactivation of several tumor suppressors. SHORT CONCLUSION: In this review we will describe new insights on the role of FoxO, PP2A, p27, BLK, PTEN and other tumor suppressors in CML pathogenesis. Finally, we will describe strategies to promote tumor suppressors reactivation in CML. PMID- 27184145 TI - Editorial: Chemical and Biological Technology for In Vivo and Molecular Imaging. PMID- 27184142 TI - Downregulation of Cdh1 signalling in spinal dorsal horn contributes to the maintenance of mechanical allodynia after nerve injury in rats. AB - BACKGROUND: Anaphase-promoting complex/cyclosome (APC/C) and its co-activator Cdh1 are important ubiquitin-ligases in proliferating cells and terminally differentiated neurons. In recent years, APC/C-Cdh1 has been reported as an important complex contributing to synaptic development and transmission. Interestingly, cortical APC/C-Cdh1 is found to play a critical role in the maintenance of neuropathic pain, but it is not clear whether APC/C-Cdh1 in spinal dorsal cord is involved in molecular mechanisms of neuropathic pain conditions. RESULTS: Immunostaining showed that Cdh1 was mainly distributed in dorsal horn neurons of the spinal cord in rats. Its expression was downregulated in the ipsilateral dorsal horn at 14 days after spared nerve injury. Rescued expression of Cdh1 in spinal cord by intrathecal administration of recombinant lentivirus encoding Cdh1 (Lenti-Cdh1-GFP) significantly attenuated spared nerve injury induced mechanical allodynia. Furthermore, rescued expression of spinal Cdh1 significantly reduced surface membrane expression of GluR1, but increased the expression of GluR1-related erythropoietin-producing human hepatocellular receptor A4 and its ligand EphrinA1 in dorsal horn of spared nerve injury-treated animals. CONCLUSIONS: This study indicates that a downregulation of Cdh1 expression in spinal dorsal horn is involved in molecular mechanisms underlying the maintenance of neuropathic pain. Upregulation of spinal Cdh1 may be a promising approach to treat neuropathic pain. PMID- 27184144 TI - A novel, bedside technique to rapidly identify umbilical cord blood units with high total nucleated cell numbers. AB - BACKGROUND: With increasing demand for umbilical cord blood units (CBUs) with total nucleated cell (TNC) counts of more than 150 * 10(7) , preshipping assessment is mandatory. Umbilical cord blood processing requires aseptic techniques and laboratories with specific air quality and cleanliness. Our aim was to establish a fast and efficient method for determining TNC counts at the obstetric ward without exposing the CBU to the environment. STUDY DESIGN AND METHODS: Data from a total of 151 cord blood donations at a single procurement site were included in this prospective study. We measured TNC counts in cord blood aliquots taken from the umbilical cord (TNCCord ), from placenta (TNCPlac ), and from a tubing segment of the sterile collection system (TNCTS ). TNC counts were compared to reference TNC counts in the CBU which were ascertained at the cord blood bank (TNCCBU ). RESULTS: TNCTS counts (173 +/- 33 * 10(7) cells; calculated for 1 unit) correlated fully with the TNCCBU reference counts (166 +/- 33 * 10(7) cells, Pearson's r = 0.97, p < 0.0001). In contrast, TNCCord and TNCPlac counts were more disparate from the reference (r = 0.92 and r = 0.87, respectively). CONCLUSIONS: A novel method of measuring TNC counts in tubing segments from the sterile cord blood collection system allows rapid and correct identification of CBUs with high cell numbers at the obstetric ward without exposing cells to the environment. This approach may contribute to cost efficacy as only CBUs with satisfactory TNC counts need to be shipped to the cord blood bank. PMID- 27184143 TI - Prediction models for cardiovascular disease risk in the general population: systematic review. AB - OBJECTIVE: To provide an overview of prediction models for risk of cardiovascular disease (CVD) in the general population. DESIGN: Systematic review. DATA SOURCES: Medline and Embase until June 2013. ELIGIBILITY CRITERIA FOR STUDY SELECTION: Studies describing the development or external validation of a multivariable model for predicting CVD risk in the general population. RESULTS: 9965 references were screened, of which 212 articles were included in the review, describing the development of 363 prediction models and 473 external validations. Most models were developed in Europe (n=167, 46%), predicted risk of fatal or non-fatal coronary heart disease (n=118, 33%) over a 10 year period (n=209, 58%). The most common predictors were smoking (n=325, 90%) and age (n=321, 88%), and most models were sex specific (n=250, 69%). Substantial heterogeneity in predictor and outcome definitions was observed between models, and important clinical and methodological information were often missing. The prediction horizon was not specified for 49 models (13%), and for 92 (25%) crucial information was missing to enable the model to be used for individual risk prediction. Only 132 developed models (36%) were externally validated and only 70 (19%) by independent investigators. Model performance was heterogeneous and measures such as discrimination and calibration were reported for only 65% and 58% of the external validations, respectively. CONCLUSIONS: There is an excess of models predicting incident CVD in the general population. The usefulness of most of the models remains unclear owing to methodological shortcomings, incomplete presentation, and lack of external validation and model impact studies. Rather than developing yet another similar CVD risk prediction model, in this era of large datasets, future research should focus on externally validating and comparing head-to-head promising CVD risk models that already exist, on tailoring or even combining these models to local settings, and investigating whether these models can be extended by addition of new predictors. PMID- 27184146 TI - Optimal growth condition of earthworms and their vermicompost features during recycling of five different fresh fruit and vegetable wastes. AB - This study aimed to promote vermicomposting performance for recycling fresh fruit and vegetable wastes (FVWs) and to assess microbial population and community of final products. Five fresh FVWs including banana peels, cabbage, lettuce, potato, and watermelon peels were chosen as earthworms' food. The fate test of earthworms showed that 30 g fresh FVWs/day was the optimal loading and the banana peels was harmful for the survival of Eisenia fetida. The followed vermicomposting test revealed lower contents of total carbon and weaker microbial activity in final vermicomposts, relative to those in compared systems without earthworms worked. The leachate from FVWs carried away great amounts of nutrients from reactors. Additionally, different fresh FVWs displayed dissimilar stabilization process. Molecular biological approaches revealed that earthworms could broaden bacterial diversity in their products, with significant greater populations of actinobacteria and ammonia oxidizing bacteria than in control. This study evidences that vermicomposting efficiency differs with the types and loadings of fresh FVWs and vermicomposts are rich in agricultural probiotics. PMID- 27184147 TI - Influence of supporting electrolyte in electricity generation and degradation of organic pollutants in photocatalytic fuel cell. AB - This study investigated the effect of different supporting electrolyte (Na2SO4, MgSO4, NaCl) in degradation of Reactive Black 5 (RB5) and generation of electricity. Zinc oxide (ZnO) was immobilized onto carbon felt acted as photoanode, while Pt-coated carbon paper as photocathode was placed in a single chamber photocatalytic fuel cell, which then irradiated by UV lamp for 24 h. The degradation and mineralization of RB5 with 0.1 M NaCl rapidly decreased after 24 h irradiation time, followed by MgSO4, Na2SO4 and without electrolyte. The voltage outputs for Na2SO4, MgSO4 and NaCl were 908, 628 and 523 mV, respectively, after 24-h irradiation time; meanwhile, their short-circuit current density, J SC, was 1.3, 1.2 and 1.05 mA cm(-2), respectively. The power densities for Na2SO4, MgSO4 and NaCl were 0.335, 0.256 and 0.245 mW cm(-2), respectively. On the other hand, for without supporting electrolyte, the voltage output and short-circuit current density was 271.6 mV and 0.055 mA cm(-2), respectively. The supporting electrolyte NaCl showed greater performance in degradation of RB5 and generation of electricity due to the formation of superoxide radical anions which enhance the degradation of dye. The mineralization of RB5 with different supporting electrolyte was measured through spectrum analysis and reduction in COD concentration. PMID- 27184148 TI - Water-soluble ionic species of coarse and fine particulate matter and gas precursor characteristics at urban and rural sites of central Taiwan. AB - Coarse and fine particulate matter (PM) were taken by a dichotomous sampler, and gas precursors were determined by a denuder sampler at two stations in central Taiwan. Water-soluble ionic constituents of PM and their precursor gases were analyzed by ionic chromatograph. In summer, the daytime/nighttime PM10 concentrations were 37 +/- 10/41 +/- 18 MUg m(-3) and 36 +/- 14/34 +/- 18 MUg m( 3) for Xitun and Jhushan, respectively. Average PM10 concentration in winter was 1.55 and 1.76 times that of summer for Xitun and Jhushan, respectively. PM mass concentrations were similar for both stations, although one station is located in the downtown area of Taichung, and the other is in a rural area with no heavy pollution sources. Water-soluble ionic species content was 38-53 % of PM2.5 and 43-48 % of PM10 mass concentration. HNO3, HCl, and SO2 were high in the daytime; the daytime-to-nighttime concentration ratio was 3.75-6.88 for HNO3,1.7-7.8 for HCl, and 1.45-2.77 for SO2. High NH3 levels were determined in the area, especially in winter, which could be a precursor of NH4 (+) to form particulate matter. In Xitun, motor vehicles downtown and in the industrial district could be sources of air pollution. In contrast, there are few industrial sources at Jhushan; therefore, the transport of air pollutants from upwind of other regions and the accumulation of pollutants could be important PM sources at Jhushan. PMID- 27184149 TI - Geophysical, isotopic, and hydrogeochemical tools to identify potential impacts on coastal groundwater resources from Urmia hypersaline Lake, NW Iran. AB - Measurements of major ions, trace elements, water-stable isotopes, and geophysical soundings were made to examine the interaction between Urmia Aquifer (UA) and Urmia Lake (UL), northwest Iran. The poor correlation between sampling depth and Cl(-) concentrations indicated that the position of freshwater saltwater interface is not uniformly distributed in the study area, and this was attributed to aquifer heterogeneities. The targeted coastal wells showed B/Cl and Br/Cl molar ratios in the range of 0.0022-2.43 and 0.00032-0.28, respectively. The base-exchange index (BEI) and saturation index (SI) calculations showed that the salinization process followed by cation-exchange reactions mainly controls changes in the chemical composition of groundwater. All groundwater samples are depleted with respect to delta(18)O (-11.71 to -9.4 0/00) and deltaD (-66.26 to 48.41 0/00). The delta(18)O and deltaD isotope ratios for surface and groundwater had a similar range and showed high deuterium excess (d-excess) (21.11 to 31.16 0/00). The high d-excess in water samples is because of incoming vapors from the UL mixed with an evaporated moisture flux from the Urmia mainland and incoming vapors from the west (i.e., Mediterranean Sea). Some saline samples with low B/Cl and Br/Cl ratios had depleted delta(18)O and deltaD. In this case, due to freshwater flushing, the drilled wells in the coastal playas and salty sediments could have more depleted isotopes, more Cl(-), and consequently smaller B/Cl and Br/Cl ratios. Moreover, the results of hydrochemical facies evolution (HFE) diagram showed that because of the existence fine-grained sediments saturated with high density saltwater in the coastal areas that act as a natural barrier, increasing the groundwater exploitation leads to movement of freshwaters from recharge zones in the western mountains not saltwater from UL. The highly permeable sediments at the junction of the rivers to the lake are characterized by low hydraulic gradient and high hydraulic conductivity. These properties enhance the salinization of groundwater observed in the study area. The main factors influencing the salinity are base-exchange reactions, invasion of highly diluted saltwater, dissolution of salty pans, and water chemistry evolution along flow paths. PMID- 27184150 TI - Effects of oxygen and weak magnetic field on Fe(0)/bisulfite system: performance and mechanisms. AB - The performance and mechanisms of 4-nitrophenol (4-NP) degradation by the Fe(0)/bisulfite system were systematically investigated for the first time. The evidences presented in this study verified that O2 was a crucial factor that affected the mechanism of Fe(0)/bisulfite-driven 4-NP degradation. In the Fe(0)/bisulfite/O2 system, Fe(0) acted as a supplier of Fe(2+) to catalyze bisulfite oxidation that induced a chain reaction to produce reactive radicals for 4-NP degradation. While under N2 purging condition, bisulfite worked as a specified reductant that facilitated the transformation of Fe(3+) to nascent Fe(2+) ions, which principally accounted for the reductive removal of 4-NP. The application of a weak magnetic field (WMF) efficiently improved the removal rate of 4-NP and did not alter the mechanisms in both Fe(0)/bisulfite/O2 and Fe(0)/bisulfite/N2 processes. The secondary radicals, HO(.), SO4 (.-), and SO5 (. ), were considered as the most possible active oxidants contributing to the oxidative removal of 4-NP and even partial mineralization under an oxic condition. Compared with anoxic conditions, the performance removal of 4-NP by the WMF-Fe(0)/bisulfite/O2 system showed less pHini dependence. To facilitate the application of WMF-Fe(0)/bisulfite/O2 technology in real practice, premagnetization of Fe(0) was employed to combine with bisulfite/O2 and proved to be an effective and applicable method for 4-NP removal. PMID- 27184152 TI - The use of a high-power laser on swine mitral valve chordae tendineae. AB - Worldwide, rheumatic fever remains a significant cause of mitral valve insufficiency. It is responsible for approximately 90 % of early childhood valvular surgeries in Brazil. Elongated or flail chordae are frequently responsible and require surgical correction. The purpose of this study was to analyze and compare the histological tissues of the mitral valve chordae and the mechanical resistance generated by the chordae, both with and without the application of a high-power laser. Twenty normal porcine mitral valve chordae were measured and divided randomly into the following two groups: control group (not subjected to a high-power laser) and laser group (subjected to photonic irradiation). Laser surgery was performed under controlled conditions, using following parameters: lambda = 980-nm wavelength, power = 3 W, and energy = 60 J. A mechanical test machine was used in combination with a subsequent histological study to measure chordae tensile properties. A histological analysis demonstrated a typical collagen bundle arrangement in the control group; however, under a particular reached temperature range (48), the collagen bundles assumed different arrangements in the laser group. Significant reductions in the chordae tendineae lengths and changes in their resistance in the laser group were observed, as these chordae exhibited less rigid fibers. The chordae tendineae of normal porcine valves subjected to a high-power laser exhibited its length reduction and less stiffness compared to the control group. A histological analysis of the laser treatment specimens demonstrated differences in collagen bundle spatial organization, following slight changes into tissue temperature. PMID- 27184151 TI - Muscle relaxation for individuals having tattoos removed through laser treatment: possible effects regarding anxiety and pain. AB - Effectively managing pain is vital for the well-being and satisfaction of patients undergoing dermatologic treatments involving lasers. This study investigates the potential outcome of using muscle relaxation techniques to reduce pain among people having their tattoos removed with laser treatment. This study consists of 56 participants (mean age 18.1 +/- 2.1 years) that had tattoos removed using the principle of selective photothermolysis. These participants underwent muscle relaxation before receiving the laser treatment. Their peripheral skin temperatures (PST) were measured both at the beginning and the end of the muscle relaxation period. Then, the Beck Anxiety Inventory was applied to evaluate anxiety levels. Once the laser treatment was completed, pain levels were measured using a visual analogue scale. A total of 125 person-sessions of laser treatment and psychometric assessments were performed in this study. The muscle relaxation method significantly increased the PST of the participants while reducing the levels of anxiety and pain throughout the course of the laser treatment procedure. The PST, anxiety scores, and pain scores all showed significant correlations with one another. According to the results obtained, this study proposes that muscle relaxation techniques be considered possibly auxiliary treatment options for individuals having tattoos removed through laser treatment. Additional studies with a comparison group and a larger sample size are required in the future to confirm the effectiveness of such intervention. PMID- 27184153 TI - Laser Doppler flowmetry: reproducibility, reliability, and diurnal blood flow variations. AB - The aim of this investigation was (1) to evaluate the reliability of laser Doppler flowmetry (LDF) taking into consideration the use of a silicone splint and the inclination of the probe towards the buccal surface of a human tooth and (2) to determine whether diurnal variations of pulpal blood flow can be registered by means of LDF. Forty-one splints were made by one and the same principal investigator for the registration of pulpal blood flow in vivo in a maxillary right central incisor. Thirty dentists, without experience in LDF recording, were then asked to drill a right-angled shaft in a pre-manufactured splint with a referral point at 2 mm from the enamel-cement border central on the buccal surface of the right central upper incisor. The remaining 11 splints were handled by the principal investigator. The shafts in the 30 splints were analysed using Cone Beam CT imaging of the axial and sagittal angles and compared these to the 11 shafts prepared by the trained principal investigator. LDF was recorded for 90 s in each splint and statistically analysed. LDF values without the use of a splint were statistically significantly different (p < 0.05) and the variance was greater, indicating the superiority of splint use. Significant diurnal variations on LDF values were observed, indicating that special attention should be paid to registration during the day, especially when multiple measurements are to be compared. PMID- 27184155 TI - Investigations of initial airtightness after non-anatomic resection of lung parenchyma using a thulium-doped laser with different optical fibres. AB - Lung metastases in healthy patients should be removed non-anatomically whenever possible. This can be done with a laser. Lung parenchyma can be cut very well, because of its high energy absorption at a wavelength of 1940 nm. A coagulation layer is created on the resected surface. It is not clear, whether this surface also needs to be sutured to ensure that it remains airtight even at higher ventilation pressures. It would be helpful, if suturing could be avoided, because the lung can become too puckered, especially with multiple resections, resulting in considerable restriction. We carried out our experiments on isolated and ventilated paracardiac lung lobes of pigs. Non-anatomic resection was carried out reproducibly using three different thulium laser fibres (230, 365 and 600 MUm) at two different laser power levels (10 W, 30 W) and three different resection depths (0.5, 1.0 and 2.0 cm). Initial airtightness was investigated while ventilating at normal frequency. We also investigated the bursting pressures of the resected areas by increasing the inspiratory pressure. When 230- and 365-MUm fibres were used with a power of 10 W, 70 % of samples were initially airtight up to a resection depth of 1 cm. This rate fell at depths of up to 2 cm. All resected surfaces remained airtight during ventilation when 600-MUm fibres were used at both laser power levels (10 and 30 W). The bursting pressures achieved with 600-MUm fibres were higher than with the other fibres used: 0.5 cm, 41.6 +/- 3.2 mbar; 1 cm, 38.2 +/- 2.5 mbar; 2 cm, 33.7 +/- 4.8 mbar. As laser power and thickness of laser fibre increased, so the coagulation zone became thicker. With a 600-MUm fibre, it measured 145.0 +/- 8.2 MUm with 10 W power and 315.5 +/- 6.4 MUm with 30 W power. Closure with sutures after non-anatomic resection of lung parenchyma is not necessary when a thulium laser is used provided a 600-MUm fibre and adequate laser power (30 W) are employed. At deeper resection levels, the risk of cutting small segmental bronchi is considerably increased. They must always be closed with sutures. PMID- 27184156 TI - In vitro validation of a hand-held optical reflectometer to measure clinically observed erosive tooth wear. AB - In this study, we analyzed a newly developed optical reflectometer for measuring erosive tooth wear (ETW) in vitro. Three examiners independently assessed the labial surface of 80 deciduous canines and 75 permanent incisors. One examiner performed visual examinations (BEWE), and the other two used the optical pen-size reflectometer to measure surface reflection intensity (SRI) on the same labial surfaces. The examinations were made in duplicate with at least 1 week interval. Intra- and inter-rater agreements were calculated using weighted kappa analysis for BEWE, and intra-class correlation coefficients (ICC) as well as Bland-Altman plots for SRI. The teeth were separated into without (BEWE 0) or with (BEWE 1-3) ETW, and SRI cut-off points were calculated. Intra-rater agreement for the visual examination was 0.46 and 0.82 for deciduous and permanent teeth, respectively. Inter-rater and intra-rater agreement for SRI were good (ICC > 0.7; p < 0.001). SRI measurements produced high specificity values for deciduous and permanent teeth (>=0.74 and >= 0.84, respectively), and lower sensitivity values (>=0.37 and >= 0.64, respectively), but permanent teeth had generally higher SRI values (p < 0.05). We observed a significant association between BEWE and SRI (p < 0.05). The optical pen-size reflectometer was able to adequately differentiate ETW on permanent teeth, with highly reliable and reproducible measurements, but ETW on deciduous teeth was less accurately differentiated. The reflectometer is a good candidate for clinical research. PMID- 27184154 TI - Combined pulsed dye and CO2 lasers in the treatment of angiolymphoid hyperplasia with eosinophilia. AB - Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon dermatosis of unknown etiology that manifests as characteristic red nodules and papules with a predilection for the scalp and periauricular region. Treatment is required for both esthetic and functional reasons, as lesions may ulcerate and bleed. Many treatment approaches have been reported, including excision, systemic medical approaches, topical or intralesional therapies, and non-invasive modalities including cryotherapy, electrosurgery, and laser. Treatments have exhibited variable efficacy, and the recurrence rate is 100 %. We report the combination of pulsed dye laser and CO2 laser in the treatment of ALHE in 14 patients. All patients exhibited clinical response after a mean of 2.4 +/- 0.4 treatment sessions. The clinical efficacy of the combined treatment, together with its well tolerated nature, render the use of pulsed dye laser in combination with CO2 laser, a viable treatment for debulking ALHE lesions. Ongoing maintenance treatments are needed to due to the high degree of relapse. PMID- 27184157 TI - Evaluation of 660 nm LED light irradiation on the strategies for treating experimental periodontal intrabony defects. AB - This study aims to investigate the therapeutic value of 660 nm light-emitting diode (LED) light irradiation on the strategies for treating experimental periodontal intrabony defects in vivo. Large-sized periodontal intrabony defects were created bilaterally on the mesial aspect of the maxillary second molars of 48 Sprague-Dawley rats, and the rats were equally divided into four treatment groups with primary wound intention (n = 6/treatment/time point), including open flap debridement alone (OD), barrier membrane alone (MB), xenograft alone (BG), and xenograft plus barrier membrane (MG). Each group received daily 0 or 10 J/cm(2) LED light irradiation. The animals were sacrificed after 1 or 4 weeks. The treatment outcome was evaluated by gross observation of wound dehiscence and healing, micro-CT imaging for osteogenesis, and histological assessments for inflammatory cell infiltration and periodontal reattachment. With LED light irradiation, the extent of wound dehiscence was reduced, wound closure was accelerated, epithelial downgrowth was prevented, inflammation was reduced, and periodontal reattachment was promoted in all treatment strategies. Significant reduction of inflammation with LED light irradiation was noted at 1 week in the groups BG and MG (p < 0.05). Osteogenesis was significantly promoted only in the group OD at both time points (p < 0.05). Our study showed that 660 nm LED light accelerates mucoperiosteal flap healing and periodontal reattachment. However, the enhancement of osteogenesis appeared to be limited while simultaneously treating with a barrier membrane or xenograft. PMID- 27184158 TI - Specific allergen immunotherapy for the treatment of atopic eczema: a Cochrane systematic review. AB - BACKGROUND: Specific allergen immunotherapy (SIT) is an effective allergy treatment, but it is unclear whether SIT is effective for atopic eczema (AE). We undertook a systematic review to assess SIT efficacy and safety for treating AE. METHODS: We searched databases, ongoing clinical trials registers, and conference proceedings up to July 2015. Randomized controlled trials (RCTs) of SIT using standardized allergen extracts, compared with placebo/control, for treating AE in patients with allergic sensitization were eligible. RESULTS: We identified 12 eligible trials with 733 participants. Interventions included subcutaneous (six trials), sublingual (four trials), oral or intradermal SIT in children/adults allergic to house dust mite (10 trials), grass pollen or other inhalants. Risk of bias was moderate, with high loss to follow-up and nonblinding as the main concerns. For our primary outcomes, three studies (208 participants) reported no significant difference - patient-reported global disease severity improvement RR 0.75 (95% CI 0.45, 1.26); and eczema symptoms mean difference -0.74 on a 20-point scale (95% CI -1.98, 0.50). Two studies (85 participants) reported a significant difference - SIT improved global disease severity RR 2.85 (95% CI 1.02, 7.96); and itch mean difference -4.20 on a 10-point scale (95% CI -3.69, -4.71). Meta analysis was limited due to extreme statistical heterogeneity. For some secondary outcomes, meta-analyses showed benefits for SIT, for example investigator-rated improvement in eczema severity RR 1.48 (95% CI 1.16, 1.88; six trials, 262 participants). We found no evidence of adverse effects. The overall quality of evidence was low. CONCLUSION: We found no consistent evidence that SIT is effective for treating AE, but due to the low quality of evidence further research is needed to establish whether SIT has a role in AE treatment. PMID- 27184159 TI - Dirac Cellular Automaton from Split-step Quantum Walk. AB - Simulations of one quantum system by an other has an implication in realization of quantum machine that can imitate any quantum system and solve problems that are not accessible to classical computers. One of the approach to engineer quantum simulations is to discretize the space-time degree of freedom in quantum dynamics and define the quantum cellular automata (QCA), a local unitary update rule on a lattice. Different models of QCA are constructed using set of conditions which are not unique and are not always in implementable configuration on any other system. Dirac Cellular Automata (DCA) is one such model constructed for Dirac Hamiltonian (DH) in free quantum field theory. Here, starting from a split-step discrete-time quantum walk (QW) which is uniquely defined for experimental implementation, we recover the DCA along with all the fine oscillations in position space and bridge the missing connection between DH-DCA QW. We will present the contribution of the parameters resulting in the fine oscillations on the Zitterbewegung frequency and entanglement. The tuneability of the evolution parameters demonstrated in experimental implementation of QW will establish it as an efficient tool to design quantum simulator and approach quantum field theory from principles of quantum information theory. PMID- 27184160 TI - Item Response Theory Analysis of the Anxiety and Mood Disorders in Clinic Referred Children. AB - There is evidence that the major anxiety and depressive disorders could reflect a single underlying internalization factor. For a group of 1,031 clinic-referred children, the study examined support for this factor, and used the two-parameter logistic model to examine the item response theory properties of the disorders in this factor. For the set of anxiety and depressive disorders, confirmatory factor analysis supported a one-factor model. The two-parameter logistic model analysis indicated that all the internalizing disorders in this factor were strong discriminators of the internalizing dimension. Also, they measured more of the internalizing dimension and with more precision in the upper half of the trait continuum. There was also support for the convergent validity of the internalizing dimension, in that it had large-to-medium effect size correlations with internalizing scores of other measures. The implications of the findings for clinical practice and clinical classification are discussed. PMID- 27184161 TI - Implementing Dynamic Assessments in Psychotherapy. AB - In this article, we organize multimethod, multitimescale data around the interpersonal situation, a conceptual framework that can be used to integrate personality, psychopathology, and psychotherapy constructs in order to guide the assessment of clinical dynamics. We first describe the key variables of the interpersonal situation model and articulate methods for assessing those variables as they manifest (a) across different levels of personality, (b) across situations, and (c) within situations. We next use a case to demonstrate how to assess aspects of the interpersonal situation in a manner that enhances case conceptualization and facilitates the evaluation of clinical hypotheses. We also use this case to highlight challenges and decisions involved in implementing dynamic assessment in psychotherapy. We conclude by outlining areas in need of further exploration toward a more sophisticated approach to clinical practice that involves the routine assessment of dynamic processes. PMID- 27184163 TI - Characteristics of peripheral blood CD4+CD25+ regulatory T cells and related cytokines in severe atopic dermatitis. AB - Regulatory T cells (Tregs) have been suggested to play a role in the pathogenesis of atopic dermatitis (AD). However, alterations in the ability of Tregs remain to be determined. To investigate the expression of various surface receptors on CD4(+)CD25(high) regulatory T cells and to investigate their capacity for inhibiting the proliferation of CD4(+) CD25(-) effector T cells (Teffs). Peripheral blood samples were obtained from 15 patients with severe atopic dermatitis (AD) and 20 control subjects. FACs was then carried out to analyze the expression levels of FoxP3, CD152 (CTLA-4), CD39, CD73, CD223 (LAG-3), CCR4, CCR5, and CCR10 on Tregs. The proliferative responses of Teffs were assessed in the absence or presence of autologous Tregs and the TGF-beta1 and IL-10 levels in the culture supernatant and sera were detected by enzyme-linked immunosorbent assay (ELISA). The CD152, CD39, CD73, CCR4, and CCR5 expression levels on Tregs were higher in patients with severe AD than in the controls. Tregs showed an attenuated suppressive function of the proliferation of autologous Teffs in severe AD. The concentrations of IL-10 and TGF-beta in the culture supernatants of Tregs were lower in the AD group than in the control. The attenuated ability of Tregs to suppress Teff proliferation may be responsible for the autoimmune reaction of severe AD. PMID- 27184162 TI - Airway epithelial cell exposure to distinct e-cigarette liquid flavorings reveals toxicity thresholds and activation of CFTR by the chocolate flavoring 2,5 dimethypyrazine. AB - BACKGROUND: The potential for adverse respiratory effects following exposure to electronic (e-) cigarette liquid (e-liquid) flavorings remains largely unexplored. Given the multitude of flavor permutations on the market, identification of those flavor constituents that negatively impact the respiratory tract is a daunting task. In this study we examined the impact of common e-liquid flavoring chemicals on the airway epithelium, the cellular monolayer that provides the first line of defense against inhaled particulates, pathogens, and toxicants. METHODS: We used the xCELLigence real-time cell analyzer (RTCA) as a primary high-capacity screening tool to assess cytotoxicity thresholds and physiological effects of common e-liquid flavoring chemicals on immortalized human bronchial epithelial cells (16HBE14o-). The RTCA was used secondarily to assess the capability of 16HBE14o- cells to respond to cellular signaling agonists following a 24 h exposure to select flavoring chemicals. Finally, we conducted biophysical measurements of well-differentiated primary mouse tracheal epithelial (MTE) cells with an Ussing chamber to measure the effects of e-cigarette flavoring constituents on barrier function and ion conductance. RESULTS: In our high-capacity screens five of the seven flavoring chemicals displayed changes in cellular impedance consistent with cell death at concentrations found in e-liquid. Vanillin and the chocolate flavoring 2,5 dimethylpyrazine caused alterations in cellular physiology indicative of a cellular signaling event. At subcytotoxic levels, 24 h exposure to 2,5 dimethylpyrazine compromised the ability of airway epithelial cells to respond to signaling agonists important in salt and water balance at the airway surface. Biophysical measurements of 2,5-dimethylpyrazine on primary MTE cells revealed alterations in ion conductance consistent with an efflux at the apical airway surface that was accompanied by a transient loss in transepithelial resistance. Mechanistic studies confirmed that the increases in ion conductance evoked by 2,5 dimethylpyrazine were largely attributed to a protein kinase A-dependent (PKA) activation of the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel. CONCLUSIONS: Data from our high-capacity screening assays demonstrates that individual e-cigarette liquid flavoring chemicals vary in their cytotoxicity profiles and that some constituents evoke a cellular physiological response on their own independent of cell death. The activation of CFTR by 2,5 dimethylpyrazine may have detrimental consequences for airway surface liquid homeostasis in individuals that use e-cigarettes habitually. PMID- 27184164 TI - Cold-inducible RNA binding protein regulates mucin expression induced by cold temperatures in human airway epithelial cells. AB - Mucus overproduction is an important manifestation of chronic airway inflammatory diseases, however, the mechanisms underlying the association between cold air and mucus overproduction remain unknown. We found that the expression of the cold inducible RNA binding protein (CIRP) was increased in patients with chronic obstructive pulmonary disease (COPD). In the present study, we tested whether CIRP was involved in inflammatory factors and mucin5AC (MUC5AC) expression after cold stimulation and investigated the potential signaling pathways involved in this process. We found that CIRP was highly expressed in the bronchi of COPD patients. The expression of CIRP, interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) were increased, and the CIRP was localized in cytoplasm after cold stimulation. MUC5AC mRNA and protein expression levels were elevated in a temperature- and time-dependent manner after cold stimulation and were associated with the phosphorylation of ERK and NF-kappaB, which reflected their activation. These responses were suppressed by knockdown of CIRP with a specific siRNA or the ERK and NF-kappaB inhibitors. These results demonstrated that CIRP was expressed in the bronchi of human COPD patients and was involved in inflammatory factors and MUC5AC expression after cold stimulation through the ERK and NF-kappaB pathways. PMID- 27184124 TI - Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index. AB - The maintenance of normal body weight is disrupted in patients with anorexia nervosa (AN) for prolonged periods of time. Prior to the onset of AN, premorbid body mass index (BMI) spans the entire range from underweight to obese. After recovery, patients have reduced rates of overweight and obesity. As such, loci involved in body weight regulation may also be relevant for AN and vice versa. Our primary analysis comprised a cross-trait analysis of the 1000 single nucleotide polymorphisms (SNPs) with the lowest P-values in a genome-wide association meta-analysis (GWAMA) of AN (GCAN) for evidence of association in the largest published GWAMA for BMI (GIANT). Subsequently we performed sex-stratified analyses for these 1000 SNPs. Functional ex vivo studies on four genes ensued. Lastly, a look-up of GWAMA-derived BMI-related loci was performed in the AN GWAMA. We detected significant associations (P-values <5 * 10-5, Bonferroni corrected P<0.05) for nine SNP alleles at three independent loci. Interestingly, all AN susceptibility alleles were consistently associated with increased BMI. None of the genes (chr. 10: CTBP2, chr. 19: CCNE1, chr. 2: CARF and NBEAL1; the latter is a region with high linkage disequilibrium) nearest to these SNPs has previously been associated with AN or obesity. Sex-stratified analyses revealed that the strongest BMI signal originated predominantly from females (chr. 10 rs1561589; Poverall: 2.47 * 10-06/Pfemales: 3.45 * 10-07/Pmales: 0.043). Functional ex vivo studies in mice revealed reduced hypothalamic expression of Ctbp2 and Nbeal1 after fasting. Hypothalamic expression of Ctbp2 was increased in diet-induced obese (DIO) mice as compared with age-matched lean controls. We observed no evidence for associations for the look-up of BMI-related loci in the AN GWAMA. A cross-trait analysis of AN and BMI loci revealed variants at three chromosomal loci with potential joint impact. The chromosome 10 locus is particularly promising given that the association with obesity was primarily driven by females. In addition, the detected altered hypothalamic expression patterns of Ctbp2 and Nbeal1 as a result of fasting and DIO implicate these genes in weight regulation. PMID- 27184165 TI - Diastolic dysfunction and cardiac troponin I decrease in aging hearts. AB - Cardiac tropnoin I (cTnI) plays a critical role in the regulation of diastolic function, and its low expression may result in cardiac diastolic dysfunction, which is the most common form of cardiovascular disorders in older adults. In this study, cTnI expression levels were determined in mice at various ages and cardiac function was measured and compared between young adult mice (3 and 10 months) and older mice (18 months). The data indicated that the cTnI levels reached a peak high in young adult hearts (3 months), but decreased in older hearts (18 months). Furthermore, the older hearts showed a significant diastolic dysfunction observed by P-V loop and echocardiography measurements. To further define the mechanism underlying the cTnI decrease in aging hearts, we tested DNA methylation and histone acetylation modifications of cTnI gene. We found that acetylation of histone near the promoter region of cTnI gene played an important role in regulation of cTnI expression in the heart at different ages. Our study indicates that epigenetic modification caused cTnI expression decrease is one of the possible causes that result in a reduced cTnI level and diastolic dysfunction in the older hearts. PMID- 27184166 TI - Problem signs in law school: Fostering attorney well-being early in professional training. AB - Attorneys suffer from high rates of stress, alcoholism, and mental health problems that are costly for the legal system and impair their abilities to serve their clients. There is some indication that these problems begin in law school. The present study assessed a cohort of law students at an American law school for their reported levels of stress, depression, anxiety, substance use, and overall adjustment/coping. Findings indicate that law students suffer from high levels of stress, anxiety, depression, and alcohol use, and that these problem behaviors fluctuate throughout the course of law school. We discuss the implications for law student/lawyer well-being and legal education. PMID- 27184167 TI - Challenges of regulatory rights of half-capacitated persons: A sociological perspective on the French Civil Code reform. AB - Democratic societies are based on the principle of equal legal capacity of all citizens to decide and act for themselves in all areas of social life. This "socio-civil capacity", which may involve both material property of an individual, as well as private life in matters ranging from health to personal relationships, is recognized by the law (both codified law and common law). These rights guarantee the autonomy and freedom of individuals in the name of respect for human dignity. Civil capacity of a person is legally diminished because his or her "natural" abilities, capacity, or competence are reduced. Recent social changes have lead to increased uses of legal measures of protection. The reasons for these changes are complex and they are accompanied by legislative reforms that modify the rights of half-capacitated persons. In this article, we examine certain issues of civil capacity rights based on the French example. We start present a perspective of the historical definition and practice of these rights as well as their democratization. PMID- 27184168 TI - Meta-Analysis of the Long-Term Effect of Routine Aspiration Thrombectomy in Patients Undergoing Primary Percutaneous Coronary Intervention. AB - American College of Cardiology Foundation/American Heart Association guidelines no longer recommend the use of routine aspiration thrombectomy during primary percutaneous coronary intervention (PCI). This is based on evidence from recent randomized controlled trials (RCTs) that suggests that the long-term benefits of aspiration thrombectomy were previously overestimated. We conducted a systematic review and meta-analysis of RCTs to examine the effect of routine aspiration thrombectomy during primary PCI versus primary PCI alone on markers of reperfusion immediately after PCI and on clinical outcomes at >=6 months. We systematically searched Medline, EMBASE, and the Cochrane Library of Clinical trials for RCTs published in English or French with follow-up >=6 months. Data were pooled using random-effects models. Eighteen publications (containing data from 14 RCTs, n = 20,285) met our inclusion criteria. Aspiration thrombectomy was associated with higher rates of ST-segment resolution (relative risk [RR] 1.22, 95% CI 1.07 to 1.40) and myocardial blush grade 3 (RR 1.30, 95% CI 1.01 to 1.67) and a reduced risk of no reflow immediately after PCI (RR 0.63, 95% CI 0.40 to 0.98). However, thrombectomy was not associated with our primary outcome of all cause mortality at longest available follow-up (RR 0.92, 95% CI 0.81 to 1.04). Similar results were obtained for myocardial infarction and target vessel/lesion revascularization. Thrombectomy also increased the risk of stroke (RR 1.59, 95% CI 1.07 to 2.35). In conclusion, routine aspiration thrombectomy during primary PCI has some short-term clinical benefits but does not improve outcomes >=6 months and increases the risk of stroke. PMID- 27184171 TI - Detailed Transthoracic and Transesophageal Echocardiographic Analysis of Mitral Leaflets in Patients Undergoing Mitral Valve Repair. AB - A recent histological study of resected scallop-P2 in mitral valve (MV) prolapse, showed that chordae tendinae may be missing or hidden in superimposed fibrous tissue of the leaflets, contributing to their thickening. This may have relevant clinical implication because detailed analysis of MV leaflets has a central role in the evaluation of patients undergoing repair. The aim of this study was to analyze MV leaflets focusing on thickness of prolapsing segments and the presence of chordal rupture (CR). We enrolled 246 patients (age 63 +/- 13 years, 72 men) with isolated P2 prolapse and also 50 age-matched patients with normal MV anatomy as control group. Transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) were retrospectively analyzed to quantify the length and the proximal and distal thickness of both anterior (A2) and posterior (P2) MV scallops. Measurements were performed at end diastole in the standard TTE and TEE views. TTE and TEE measurements were feasible in all cases. Echocardiographically 176 patients had CR (group A), 45 had no rupture (group B), and 25 had an uncertain diagnosis (group C). All pathological groups showed thickening and elongation of involved leaflets versus normal, whereas no differences in leaflets characteristics were found among MV groups. Most patients undergoing MV repair had CR with thickening of the prolapsed segment. These findings are in agreement with recent histological studies showing superimposed fibrous tissue on MV leaflets partially including ruptured chordae. This may also explain that in cases without ruptured chordae, thickness of the leaflets is markedly increased (hidden chordae?). In conclusion, detailed analysis of MV apparatus may further improve knowledge of these patients and may influence surgical timing. PMID- 27184172 TI - Relation of Nonvalvular Atrial Fibrillation to Body Mass Index (from the SPORTIF Trials). AB - Obesity is well-established as a major cardiovascular (CV) risk factor. Obesity confers a greater risk for developing atrial fibrillation (AF), but the relation between obesity and established nonvalvular AF for stroke and all-cause death is still unclear. To ascertain the prevalence of overweight and obesity in patients with nonvalvular AF, their influence on adverse events, and the relation with anticoagulation control, we performed this post hoc analysis of the pooled Stroke Prevention using an Oral Thrombin Inhibitor in patients with atrial Fibrillation (SPORTIF) III and V data sets. For this study, we analyzed all patients assigned to the warfarin arm with data on body mass index (BMI). Time in therapeutic range was used as an index of the quality of anticoagulation control. The 3,630 patients eligible for this analysis were categorized as follows: (1) BMI 18.5 to 24.9 ("normal weight") in 24.1%; (2) BMI 25.0 to 29.9 ("overweight") in 39.8%; and BMI >=30 ("obese") in 36.1%. Both overweight (hazard ratio [HR] 0.70) and obese (HR 0.59) categories were inversely associated with the composite outcome of stroke/all-cause death. A similar inverse association was seen for the end point of stroke (HR 0.61 and 0.47, respectively). Good anticoagulation control also attenuated the association between BMI categories and outcomes. In patients with time in therapeutic range >70%, BMI category was not significantly associated with the composite outcome of stroke/death and stroke. Stroke and all cause death progressively reduced in overweight and obese anticoagulated patients with AF. The inverse relation of BMI categories to the risk of stroke and all cause death was mitigated by good anticoagulation control. PMID- 27184169 TI - Usefulness of Predilation Before Transcatheter Aortic Valve Implantation. AB - Balloon predilation is historically considered a requirement before performing transcatheter aortic valve implantation (TAVI). As the procedure has evolved, it has been questioned whether it is actually needed, but data are lacking on mid term outcomes. The aim of this study was to evaluate the effect of balloon predilation before TAVI. A total of 517 patients who underwent transfemoral TAVI from November 2007 to October 2015 were analyzed. The devices implanted included the Medtronic CoreValve (n = 216), Medtronic Evolut R (n = 30), Edwards SAPIEN XT (n = 210), and Edwards SAPIEN 3 (n = 61). Patients were divided into 2 groups depending on whether pre-implantation balloon aortic valvuloplasty (pre-BAV) was performed (n = 326) or not (n = 191). Major adverse cardiac and cerebrovascular events (MACCE) were primarily evaluated. Propensity score matching was used to adjust for differences in baseline characteristics and potential confounders (n = 113 pairs). In the overall cohort, patients without pre-BAV had a significantly higher MACCE rate at 30 days, driven by a higher incidence of stroke (0.3% pre BAV vs 3.7% no-pre-BAV, p <0.01). MACCE and mortality at 1 year were, however, similar in both groups. Independent predictors of MACCE at 1 year included serum creatinine, NYHA class 3 to 4, logistic European System for Cardiac Operative Risk Evaluation, and postdilation. Of note, the postdilation rate was higher in the no-pre-BAV group (21.5% pre-BAV vs 35.6% no-pre-BAV, p <0.001). After propensity score matching, there were no differences in MACCE between the 2 groups. In conclusion, this study showed that, in selected patients and with specific transcatheter valves, TAVI without pre-BAV appears to be associated with similar mid-term outcomes compared with TAVI with pre-BAV, but it may increase the need for postdilation. PMID- 27184170 TI - Efficacy and Safety of Alirocumab in Japanese Subjects (Phase 1 and 2 Studies). AB - We assessed the safety and tolerability of ascending single doses of alirocumab in healthy Japanese subjects and evaluated the effect of alirocumab at 3 doses (50, 75, 150 mg) on low-density lipoprotein cholesterol (LDL-C) reduction in patients with primary hypercholesterolemia on atorvastatin. A randomized, single ascending-dose study of alirocumab (100, 150, 250, or 300 mg) or placebo (3:1 ratio), administered subcutaneously, was conducted in 32 healthy Japanese men. The phase 2, randomized, double-blind, placebo-controlled, parallel-group study was performed in patients with primary hypercholesterolemia (defined as calculated LDL-C >=100 mg/dl [2.6 mmol/l]) who were on a stable dose of atorvastatin (5 to 20 mg). Patients were randomized to alirocumab (50, 75, or 150 mg) or placebo (in single 1.0-ml injection volumes) administered every 2 weeks (Q2W) for 12 weeks; the primary outcome was the mean percent change in calculated LDL-C from baseline to week 12. Single subcutaneous administration of alirocumab in healthy subjects was well tolerated over 15 weeks and resulted in highest mean percent reductions in LDL-C from baseline of approximately 40% to 60%. In the multiple-dose study, least-square mean (SE) changes in calculated LDL-C concentrations from baseline to week 12 were -54.8% (3.1%) for alirocumab 50 mg, 62.3% (3.1%) for alirocumab 75 mg, and -71.7% (3.1%) for alirocumab 150 mg, with a least-square mean (SE) difference versus placebo of -52.2% (4.3%), -59.6% (4.3%), and -69.1% (4.3%), respectively (all p <0.0001). In conclusion, alirocumab was well tolerated and significantly reduced LDL-C concentrations in Japanese patients with primary hypercholesterolemia on atorvastatin. PMID- 27184173 TI - Feasibility and Safety of Transcatheter Aortic Valve Implantation Performed Without Intensive Care Unit Admission. AB - Admission to the intensive care unit (ICU) is a standard of care after transcatheter aortic valve implantation (TAVI); however, the improvement of the procedure and the need to minimize the unnecessary use of medical resources call into question this strategy. We evaluated prospectively 177 consecutive patients who underwent TAVI. Low-risk patients, admitted to conventional cardiology units, had stable clinical state, transfemoral access, no right bundle branch block, permanent pacing with a self-expandable valve, and no complication occurring during the procedure. High-risk patients included all the others transferred to ICU. In-hospital events were the primary end point (Valve Academic Research Consortium 2 criteria). The mean age of patients was 83.5 +/- 6.5 years, and the mean logistic EuroSCORE was 14.6 +/- 9.7%. The balloon-expandable SAPIEN 3 valve was mainly used (n = 148; 83.6%), mostly with transfemoral access (n = 167; 94.4%). Among the 61 patients (34.5%) included in the low-risk group, only 1 (1.6%) had a minor complication (negative predictive value 98.4%, 95% confidence interval [CI] 0.91 to 0.99). Conversely, 31 patients (26.7%) from the high-risk group had clinical events (positive predictive value 26.7%, 95% CI 0.19 to 0.35), mainly conductive disorders requiring pacemaker (n = 26; 14.7%). In multivariate analysis, right bundle branch block (odds ratio [OR] 14.1, 95% CI 3.5 to 56.3), use of the self-expandable valve without a pacemaker (OR 5.5, 95% CI 2 to 16.3), vitamin K antagonist treatment (OR 3.8, 95% CI 1.1 to 12.6), and female gender (OR 2.6, 95% CI 1.003 to 6.9) were preprocedural predictive factors of adverse events. In conclusion, our results suggested that TAVI can be performed safely without ICU admission in selected patients. This strategy may optimize efficiency and cost-effectiveness of procedures. PMID- 27184174 TI - Triglycerides and Triglyceride-Rich Lipoproteins in the Causal Pathway of Cardiovascular Disease. AB - Epidemiologic and clinical studies suggest that elevated triglyceride levels are a biomarker of cardiovascular (CV) risk. Consistent with these findings, recent genetic evidence from mutational analyses, genome-wide association studies, and Mendelian randomization studies provide robust evidence that triglycerides and triglyceride-rich lipoproteins are in the causal pathway for atherosclerotic CV disease, indicating that they may play a pathogenic role, much like low-density lipoprotein cholesterol (LDL-C). Although statins are the cornerstone of dyslipidemia management, high triglyceride levels may persist in some patients despite statin therapy. Several triglyceride-lowering agents are available, including fibrates, niacin, and omega-3 fatty acids, of which prescription omega 3 fatty acids have the best tolerability and safety profile. In clinical studies, omega-3 fatty acids have been shown to reduce triglyceride levels, but products containing both eicosapentaenoic acid and docosahexaenoic acid may increase LDL-C levels. Icosapent ethyl, a high-purity eicosapentaenoic acid-only product, does not raise LDL-C levels and also reduces triglyceride, non-high-density lipoprotein cholesterol, and triglyceride-rich lipoprotein levels. In conclusion, omega-3 fatty acids are currently being evaluated in large CV outcome studies in statin-treated patients; these studies should help to elucidate the causative role of triglycerides in atherosclerotic CV disease. PMID- 27184176 TI - The Sally-Anne test: an interactional analysis of a dyadic assessment. AB - BACKGROUND: The Sally-Anne test has been extensively used to examine children's theory of mind understanding. Many task-related factors have been suggested to impact children's performance on this test. Yet little is known about the interactional aspects of such dyadic assessment situations that might contribute to the ways in which children respond to the test questions. AIMS: To examine the interactional factors contributing to the performance of two children in the Sally-Anne test. To identify the interactional practices used by the tester administering the task and to describe how interactional features can pose challenges in the critical belief and reality questions for both the tester and the testee. METHODS & PROCEDURES: The Sally-Anne test was carried out as part of a project examining children's interactions in a technology-enhanced environment. The present study uses video recordings of two children with communication disorders (one with a current diagnosis of autism spectrum disorder [ASD]) and an adult tester. We draw on a multimodal approach to conversation analysis (CA) to examine the sequential organization of the test questions and answers. OUTCOMES & RESULTS: The children drew on diverse resources when producing responses to the test questions: responding verbally, pointing or manually handling objects. The tester treated these responses differently depending on how they were produced. When the child pointed at an object and verbally indicated their response, the tester moved on to the next question apparently accepting the child's answer. When the child manually handled an object or produced a quiet verbal response, the tester repeated the question indicating that the child's actions did not constitute an adequate response to a test question. In response to this, both children modified or changed their previous responses. Through monitoring each other, the tester and the child produced actions highly responsive to the features of each other's conduct, which underpinned the conduct of the test itself. CONCLUSIONS & IMPLICATIONS: Children's responses in the test might not be solely indicative of socio-cognitive capacities but also show orientation to interactional nuances. The study proposes that children can demonstrate diverse ways of responding to questions, yet testers may treat these as test-irrelevant behaviours if they do not correspond to the scoring criteria. A video-based CA study can broaden our understanding of children's pragmatic competencies in responsiveness that may not always embody an expected form. This can have implications for the development of future assessment tasks and revision of existing scoring practices. PMID- 27184175 TI - Effectiveness of initiating extrafine-particle versus fine-particle inhaled corticosteroids as asthma therapy in the Netherlands. AB - BACKGROUND: Most randomised clinical trials typically exclude a significant proportion of asthma patients, including those at higher risk of adverse events, with comorbidities, obesity, poor inhaler technique and adherence, or smokers. However, these patients might differentially benefit from extrafine-particle inhaled corticosteroids (ICS). This matched cohort, database study, compared the effectiveness of extrafine-particle with fine-particle ICS in a real-life population initiating ICS therapy in the Netherlands. METHODS: Data were from the Pharmo Database Network, comprising pharmacy and hospital discharge records, representative of 20 % of the Dutch population. The study population included patients aged 12 - 60, with a General Practice-recorded diagnosis for asthma (International Classification of Primary Care code R96), when available, >=2 prescriptions for asthma therapy at any time in their recorded history, and receiving first prescription of ICS therapy as either extrafine-particle (ciclesonide or hydrofluoroalkane beclomethasone dipropionate [BDP]) or fine particle ICS (fluticasone propionate or non-extrafine-particle-BDP). Patients were matched (1:1) on relevant demographic and clinical characteristics over 1 year baseline. Primary outcomes were severe exacerbation rates, risk domain asthma control and overall asthma control during the year following first ICS prescription. Secondary outcomes, treatment stability and being prescribed higher versus lower category of short-acting beta2 agonists (SABA) dose, were compared over a 1-year outcome period using conditional logistic regression models. RESULTS: Following matching, 1399 patients were selected in each treatment cohort (median age: 43 years; males: 34 %). Median (interquartile range) initial ICS doses (fluticasone-equivalents in MUg) were 160 (160 - 320) for extrafine particle versus 500 (250 - 500) for fine-particle ICS (p < 0.001). Following adjustment for residual confounders, matched patients prescribed extrafine particle ICS had significantly lower rates of exacerbations (adjusted rate ratio [95 % CI], 0.59 [0.47-0.73]), and significantly higher odds of achieving asthma control and treatment stability in the year following initiation than those prescribed fine-particle ICS, and this occurred at lower prescribed doses. Patients prescribed extrafine-particle ICS had lower odds of being prescribed higher doses of SABA (0.50 [0.44-0.57]). CONCLUSION: In this historical, matched study, extrafine-particle ICS was associated with better odds of asthma control than fine-particle ICS in patients prescribed their first ICS therapy in the Netherlands. Of importance, this was reached at significantly lower prescribed dose. PMID- 27184178 TI - Are Surgeons Born or Made? A Comparison of Personality Traits and Learning Styles Between Surgical Trainees and Medical Students. AB - OBJECTIVE: Medical students and surgical trainees differ considerably in both their preferential learning styles and personality traits. This study compares the personality profiles and learning styles of surgical trainees with a cohort of medical students specifically intent on pursuing a surgical career. DESIGN: A cross-sectional study was conducted contrasting surgical trainees with medical students specifying surgical career intent. The 50-item International Personality Item Pool Big-Five Factor Marker (FFM) questionnaire was used to score 5 personality domains (extraversion, conscientiousness, agreeableness, openness to experience, and neuroticism). The 24-item Learning Style Inventory (LSI) Questionnaire was used to determine the preferential learning styles (visual, auditory, or tactile). chi(2) Analysis and independent samples t-test were used to compare LSI and FFM scores, respectively. SETTING: Surgical trainees from several UK surgical centers were contrasted to undergraduate medical students. PARTICIPANTS: A total of 53 medical students who had specifically declared desire to pursue a surgical career and were currently undertaking an undergraduate intercalated degree in surgical sciences were included and contrasted to 37 UK core surgical trainees (postgraduate years 3-4). RESULTS: The LSI questionnaire was completed by 53 students and 37 trainees. FFM questionnaire was completed by 29 medical students and 34 trainees. No significant difference for learning styles preference was detected between the 2 groups (p = 0.139), with the visual modality being the preferred learning style for both students and trainees (69.8% and 54.1%, respectively). Neuroticism was the only personality trait to differ significantly between the 2 groups, with medical students scoring significantly higher than trainees (2.9 vs. 2.6, p = 0.03). CONCLUSIONS: Medical students intent on pursuing a surgical career exhibit similar personality traits and learning styles to surgical trainees, with both groups preferring the visual learning modality. These findings facilitate future research into potential ways of improving both the training and selection of students and junior trainees onto residency programs. PMID- 27184177 TI - Assessing Wire Navigation Performance in the Operating Room. AB - OBJECTIVE: There are no widely accepted, objective, and reliable tools for measuring surgical skill in the operating room (OR). Ubiquitous video and imaging technology provide opportunities to develop metrics that meet this need. Hip fracture surgery is a promising area in which to develop these measures because hip fractures are common, the surgery is used as a milestone for residents, and it demands technical skill. The study objective is to develop meaningful, objective measures of wire navigation performance in the OR. DESIGN: Resident surgeons wore a head-mounted video camera while performing surgical open reduction and internal fixation using a dynamic hip screw. Data collected from video included: duration of wire navigation, number of fluoroscopic images, and the degree of intervention by the surgeon's supervisor. To determine reliability of these measurements, 4 independent raters performed them for 2 cases. Raters independently measured the tip-apex distance (TAD), which reflects the accuracy of the surgical placement of the wire, on all the 7 cases. SETTING: University of Iowa Hospitals and Clinics in Iowa City, IA-a public tertiary academic center. PARTICIPANTS: In total 7 surgeries were performed by 7 different orthopedic residents. All 10 raters were biomedical engineering graduate students. RESULTS: The standard deviations for anteroposterior, lateral, and combined TAD measurements of the 10 raters were 2.7, 1.9, and 3.7mm, respectively, and interrater reliability produced a Cronbach alpha of 0.97. The interrater reliability analysis for all 9 video-based measures produced a Cronbach alpha of 0.99. CONCLUSIONS: Several video-based metrics were consistent across the 4 video reviewers and are likely to be useful for performance assessment. The TAD measurement was less reliable than previous reports have suggested, but remains a valuable metric of performance. Nonexperts can reliably measure these values and they offer an objective assessment of OR performance. PMID- 27184179 TI - The Cost of Getting Into Orthopedic Residency: Analysis of Applicant Demographics, Expenditures, and the Value of Away Rotations. AB - OBJECTIVES: Little is known about the demographics and expenditures of applicants attempting to match into the competitive field of orthopedic surgery. In attempt to better inform potential applicants, the purposes of this work are to (1) better understand the demographics of successfully matched applicants, (2) determine the monetary cost of applying, and (3) assess the value of away rotations for improving chances of a successful match. DESIGN: Prospective comparative survey. SETTING: Mayo Clinic Department of Orthopedic Surgery, Rochester, MN. PARTICIPANTS: A week following the 2015 Orthopedic Surgery Residency Match, a survey was sent to 1,091. The survey focused on applicant demographics, number of programs applied to, cost of applying, and the value of away rotations. RESULTS: A total of 408 applicants completed the survey (response rate = 37%). Of these, 312 (76%) matched and 96 (24%) did not match into a US Orthopedic Surgery Residency. Of the matched applicants, 300 (96%) were from US allopathic medical schools, 9 (3%) US Osteopathic Schools, and 3 (1%) were international graduates. Males comprised 84% of these applicants whereas 16% were female. The mean number of programs applied to was 71 (range: 20-140). On average, applicants were offered 16 interviews (range: 1-53) and they attended 11 (range: 0-12). Completing a rotation at a program increased an applicant's chances of matching into that program by a factor of 1.5 (60% vs 40%). Of the applicants who matched, most applicants matched to an orthopedic residency in the same region where the applicant attended medical school (58%). The average cost of the application was $1,664 (range: $100-$5,000) whereas the cost of interviews (travel, food, etc.) was $3,656 (range: $15-$20,000). Total expenditures ranged from $450 to $25,000 (mean = $5,415). Over 8% of matched applicants spent >$10,000. CONCLUSIONS: Gaining acceptance into orthopedic surgery residency remains a very competitive process. Away rotations appear to correlate strongly with match status; however, the process remains quite expensive for applicants. PMID- 27184180 TI - The Sex Difference in Basic Surgical Skills Learning: A Comparative Study. AB - BACKGROUND: Very little is known of sex-related differences among medical students in the acquisition of basic surgical skills at an undergraduate level. The aim of this study was to investigate the sex differences in basic surgical skills learning and the possible explanations for sex disparities within basic surgical skills education. METHODS: A didactic description of 10 surgical skills was performed, including knot tying, basic suture I, basic suture II, sterile technique, preoperative preparation, phlebotomy, debridement, laparotomy, cecectomy, and small bowel resection with hand-sewn anastomosis. The students were rated on a 100-point scale for each basic surgical skill. Later during the same semester all the students took the final theoretical examination. RESULTS: A total of 342 (male = 317 and female = 25) medical students participated in a single skills laboratory as part of their third-year medical student clerkship. The mean scores for each of the 10 surgical skills were higher in female group. The difference in sterile technique, preoperative preparation, cecectomy, and small bowel resection with hand-sewn anastomosis reached the significant level. Compared with male medical students, the mean theory examination score was significantly higher in female medical students. Approximately 76% of the (19 of 25) female students expressed their interest in pursuing a surgical career, whereas only 65.5% (207 of 317) male students wanted to be surgical professionals (p = 0.381). CONCLUSIONS: Female medical students completed basic surgical skills training more efficiently and passed the theoretical examination with significantly higher scores than male medical students. In the future, studies should be done in other classes in our institution and perhaps other schools to see if these findings are reliable or valid or just a reflection of this 1 sample. PMID- 27184182 TI - Impact of the coordination environment on the magnetic properties of single molecule magnets based on homo- and hetero-dinuclear terbium(iii) heteroleptic tris(crownphthalocyaninate). AB - A series of Tb(III) triple-decker heteroleptic crownphthalocyaninate complexes consisting of a homodinuclear compound [(15C5)4Pc]Tb[(15C5)4Pc]Tb(Pc) (), and two novel heterodinuclear compounds [(15C5)4Pc]Tb[(15C5)4Pc]Y(Pc), () and [(15C5)4Pc]Y[(15C5)4Pc]Tb(Pc) (), have been synthesized. All compounds were characterised using UV-Vis spectroscopy, HR-ESI-MS, MALDI-TOF-MS, and (1)H NMR spectroscopy, followed by exploration into the effects of lanthanide coupling and ligand field symmetry on the magnetic properties of these complexes using SQUID magnetometry. Magnetic measurements on the homonuclear Tb(III) complex () displayed non-negligible ferromagnetic coupling between magnetic ions, eliciting a high zero-field energetic barrier to the magnetic relaxation of Ueff = 229.9(0) K, while the heteronuclear Tb(III)/Y(III) complexes displayed single-ion field induced slow relaxation of the magnetization; yielding energetic barriers of Ueff = 129.8(0) K for , and 169.1(8) K for . PMID- 27184181 TI - Effects of Technological Advances in Surgical Education on Quantitative Outcomes From Residency Programs. AB - OBJECTIVES: The purpose of this article is to review the literature on current technology for surgical education and to evaluate the effect of technological advances on the Accreditation Council of Graduate Medical Education (ACGME) Core Competencies, American Board of Surgery In-Training Examination (ABSITE) scores, and American Board of Surgery (ABS) certification. DESIGN: A literature search was obtained from MEDLINE via PubMed.gov, ScienceDirect.com, and Google Scholar on all peer-reviewed studies published since 2003 using the following search queries: technology for surgical education, simulation-based surgical training, simulation-based nontechnical skills (NTS) training, ACGME Core Competencies, ABSITE scores, and ABS pass rate. RESULTS: Our initial search list included the following: 648 on technology for surgical education, 413 on simulation-based surgical training, 51 on simulation-based NTS training, 78 on ABSITE scores, and 33 on ABS pass rate. Further, 42 articles on technological advances for surgical education met inclusion criteria based on their effect on ACGME Core Competencies, ABSITE scores, and ABS certification. Systematic review showed that 33 of 42 and 26 of 42 publications on technological advances for surgical education showed objective improvements regarding patient care and medical knowledge, respectively, whereas only 2 of 42 publications showed improved ABSITE scores, but none showed improved ABS pass rates. Improvements in the other ACGME core competencies were documented in 14 studies, 9 of which were on simulation based NTS training. CONCLUSIONS: Most of the studies on technological advances for surgical education have shown a positive effect on patient care and medical knowledge. However, the effect of simulation-based surgical training and simulation-based NTS training on ABSITE scores and ABS certification has not been assessed. Studies on technological advances in surgical education and simulation based NTS training showing quantitative evidence that surgery residency program objectives are achieved are still needed. PMID- 27184183 TI - Increased N250 amplitudes for other-race faces reflect more effortful processing at the individual level. AB - The N250 and N250r (r for repetition, signaling a difference measure of priming) has been proposed to reflect the activation of perceptual memory representations for individual faces. Increased N250r and N250 amplitudes have been associated with higher levels of familiarity and expertise, respectively. In contrast to these observations, the N250 amplitude has been found to be larger for other-race than own-race faces in recognition memory tasks. This study investigated if these findings were due to increased identity-specific processing demands for other race relative to own-race faces and whether or not similar results would be obtained for the N250 in a repetition priming paradigm. Only Caucasian participants were available for testing and completed two tasks with Caucasian, African-American, and Chinese faces. In a repetition priming task, participants decided whether or not sequentially presented faces were of the same identity (individuation task) or same race (categorization task). Increased N250 amplitudes were found for African-American and Chinese faces relative to Caucasian faces, replicating previous results in recognition memory tasks. Contrary to the expectation that increased N250 amplitudes for other-race face would be confined to the individuation task, both tasks showed similar results. This could be due to the fact that face identity information needed to be maintained across the sequential presentation of prime and target in both tasks. Increased N250 amplitudes for other-race faces are taken to represent increased neural demands on the identity-specific processing of other-race faces, which are typically processed less holistically and less on the level of the individual. PMID- 27184184 TI - Editorial. PMID- 27184185 TI - Hepatitis C may enhance key amplifiers of psoriasis. AB - BACKGROUND: Multiple studies have noted an association between hepatitis C and psoriasis, but it is not known whether psoriasis is a result of treatment modalities for hepatitis C or a result of hepatitis C alone. OBJECTIVE: To examine the relationship between psoriasis and hepatitis C by measuring the expression of cathelicidin, TLR9 and IFNgamma in psoriatic lesional and non lesional skin in HCV-positive and negative psoriatic patients. METHODS: Two 2 mm punch biopsies of lesional and non-lesional skin in 10 patients who were HCV negative psoriatics and seven HCV-positive psoriatics were used to measure cathelicidin, TLR9 and IFNgamma mRNA expression by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). RESULTS: The mRNA levels of cathelicidin, TLR9 and IFNgamma were significantly higher in both non-lesional and lesional skin of HCV-positive patients with psoriasis as compared to HCV negative psoriatic patients. Additionally, the IFNgamma level in lesional skin of HCV-positive psoriatic patients was higher than the IFNgamma level seen in non lesional skin of those same patients. CONCLUSION: These findings suggest that HCV infection upregulates these inflammatory cytokines, possibly increasing susceptibility to developing psoriasis. PMID- 27184187 TI - Serum From Patients With Erectile Dysfunction and Vascular Risk Factors Triggered an Oxidative Stress-Dependent Mitochondrial Apoptotic Pathway in Ex Vivo Expanded Circulating Angiogenic Cells of Healthy Men. AB - INTRODUCTION: Serum from men with erectile dysfunction (ED) and vascular risk factors inhibits circulating mononuclear cells (MNCs) from expanding ex vivo and differentiating circulating angiogenic cells (CACs), which are putatively involved in the repair of endothelial damage. AIM: To explore the involvement of apoptosis in the inhibition of CAC differentiation from MNCs of healthy men exerted by serum from men with ED and vascular risk factors. METHODS: MNCs from healthy men were cultured in serum from 10 healthy men (median age = 45 years, 25th-75th quartiles = 38.5-48.5) and from 14 patients (median age = 58.0 years, 25th-75th quartiles = 52.5-62.0). CACs were identified by the uptake of 1,1' dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine-labeled acetylated low-density lipoprotein (DiLDL) and concomitant Ulex europaeus agglutinin I binding assessed by fluorescence microscopy. MAIN OUTCOME MEASURES: Flow cytometric evaluation of mitochondrial membrane potential, assessed with 5,5',6,6'-tetrachloro-1,1',3,3' tetraethyl-benimidazolyl carbocyanine iodide dye, and of activated caspase-8, -9, and -3 in DiLDL-positive cells. RESULTS: The number of CACs was significantly decreased by serum from patients compared with controls. This was associated with suppression of the mitochondrial membrane potential and activation of caspase-9 and -3 but not of caspase-8. This suggests an activation of the intrinsic (mitochondrial) pathway of apoptosis, whereas the death receptor activation of apoptosis was not involved. Activation of caspase-9 and -3 induced by serum from patients with ED was prevented by the exposure of MNCs to Trolox, a hydrophilic cell-permeable vitamin E analog with high antioxidant capacity. CONCLUSION: An oxidative stress-dependent mitochondrial dysfunction was triggered in ex vivo expanded CACs of healthy men by serum from men with vascular risk factors and ED, the only clinical correlate for diffuse vascular disease. The activation of apoptosis and inhibition of CAC differentiation might generate a defective mechanism of vascular repair. PMID- 27184186 TI - Cetuximab intensifies cisplatin-induced testicular toxicity. AB - Epidermal growth factor receptor (EGFR) has proliferative properties in the testis. Cetuximab, an anti-EGFR, is administered together with chemotherapy to patients with various types of cancer. This studies aim was to investigate the effect of cetuximab on testicular function. Adult male mice were injected with cetuximab (10 mg/kg), cisplatin (8 mg/kg) or a combination of both, and killed one week or one month later. The doses were chosen by human equivalent dose calculation. Testicular function was evaluated by epididymal-spermatozoa total motile count and sperm motility, weights of testes and epididymides, and the level of anti-Mullerian hormone (AMH) in the serum. Immunohistochemistry was performed to examine germ cell proliferation (Ki-67), apoptosis (Terminal transferase-mediated deoxyuridine 5-triphosphate nick-end labelling), reserve (DAZL-Deleted in azoospermia-like, Promyelocytic leukaemia zinc-finger), blood vessels (CD34) and Sertoli cells (GATA-4). Administration of cetuximab alone increased testicular apoptosis and decreased epididymal-spermatozoa total motile count over time. When added to cisplatin, cetuximab exacerbated most of the recorded testicular parameters, compared with the effect of cisplatin alone, including testis and epididymis weights, epididymal-spermatozoa total motile count, AMH concentration, meiosis and apoptosis. In conclusion, cetuximab has only a mild effect on testicular reserve, but when added to cisplatin, it exacerbates cisplatin-induced testicular toxicity. PMID- 27184189 TI - Nuclear receptor expression atlas in BMDCs: Nr4a2 restricts immunogenicity of BMDCs and impedes EAE. AB - The nuclear receptor (NR) superfamily of transcription factors regulates various key aspects of physiological processes; however, their role(s) in immune cells' function are just beginning to unravel. Although few NRs have been shown to be critical for dendritic cell (DC) function, a lack of knowledge about their complete representation in DCs has limited the ability to harness their full potential. Here, we performed a comprehensive NR expression profiling and identified the key members of NR superfamily being expressed in immature, immunogenic, and tolerogenic DCs. Comparative analysis revealed discrete changes in the expression of various NRs among the studied DC subtypes, indicating a likely role in the modulation of DC functionality. Next, we characterized Nr4a2, a member of orphan NR family, and found that it suppresses the activation of bone marrow derived dendritic cells triggered by LPS. Overexpression and knockdown of Nr4a2 demonstrated that Nr4a2 orchestrates the expression of immunoregulatory genes, hence inducing a tolerogenic phenotype in bone marrow derived dendritic cells. Furthermore, we also found that Nr4a2 provides protection from EAE by promoting an increase in Treg cells, while limiting effector T cells. Our findings suggest a previously unidentified role for Nr4a2 as a regulator of DC tolerogenicity and demonstrate its potential as therapeutic target in DC associated pathophysiologies. PMID- 27184188 TI - Pheretima aspergillum decoction suppresses inflammation and relieves asthma in a mouse model of bronchial asthma by NF-kappaB inhibition. AB - ETHNOPHARMACOLOGICAL RELEVANCE AND AIM OF THE STUDY: Guang-Pheretima, the live form of the earthworm Pheretima aspergillum, is a traditional Chinese medicine commonly used for the treatment of asthma, cough, stroke, epilepsy and other diseases due to its anti-inflammatory, anti-asthmatic, anti-seizure, thrombolytic and diuretic properties. Although Guang-Pheretima is effective in the relief of asthma, its pharmacological activity and the underlying molecular mechanisms are not fully understood. Hence, we investigated the effects of a Pheretima aspergillum decoction (PAD) against inflammation in a model of ovalbumin (OVA) induced asthma in BALB/c mice, as well as the nuclear factor-kappaB (NF-kappaB) pathway involved in this process. MATERIALS AND METHODS: OVA was used to sensitize and challenge the airway of the mice, and PAD was administrated by gavage. We measured airway hyperresponsiveness (AHR) in the mice 24h following a final methacholine challenge with whole-body plethysmography. The bronchoalveolar lavage fluid (BALF), serum and pulmonary tissues were collected 48h after the last challenge. The levels of inflammatory factors and the related mRNAs were determined by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR), respectively. The number of differential inflammatory cells in the BALF was counted. Serum total and OVA-specific IgE levels were measured with ELISA. The activation of NF-kappaB signaling in the lung was detected by western blotting. In addition, the lung tissues were stained with hematoxylin and eosin or periodic acid Schiff stain for histopathological examination. RESULTS: PAD treatment significantly alleviated AHR in the asthmatic mice, decreased the mRNA and protein levels of IL-4, IL-5 and IL-13 and downregulated IgE. In addition, PAD treatment attenuated mucus secretion and infiltration of inflammatory cells in the lung while inhibiting the activation of NF-kappaB signaling. CONCLUSIONS: PAD effectively inhibited the activation of NF kappaB signaling in the lungs of mice with OVA-induced asthma, and mitigated AHR and Th2 type inflammatory reactions. Therefore, PAD may serve as a drug candidate for asthma treatment. PMID- 27184190 TI - Iodine Nutritional Status in Schoolchildren from Public Schools in Brazil: A Cross-Sectional Study Exposes Association with Socioeconomic Factors and Food Insecurity. AB - INTRODUCTION: National programs of salt iodization were implemented in Brazil to combat iodine deficiency (ID) in children of school age. Currently, there are limited data in Brazil on those still vulnerable to this deficiency and the state of nutritional iodine status in the northeast region of Brazil, where children are vulnerable to malnutrition. OBJECTIVE: The aim of this study was to analyze the iodine nutritional status, household food insecurity, socioeconomic and demographic characteristics among schoolchildren from the public school system living in state the state of Bahia, Brazil. METHODS: A cross-sectional study was conducted on 1419 schoolchildren in Bahia between the ages of 6 and 14 years old. Anthropometric parameters, urinary iodine concentrations (UIC), and thyrotropin (TSH) measurements were evaluated from blood spots on filter paper. RESULTS: The mean UIC was 206.4 +/- 80.5 MUg/L, with a median of 221.6 MUg/L, indicating sufficient iodine intake in the region. Low urinary iodide concentration (<100 MUg/L) was detected in 12.3% of the schoolchildren (n = 174), with 6.2% with mild (<100 MUg/L), 3.0% with moderate (20-49 MUg/L), and 3.1% with severe ID (<20 MUg/L). Moreover, 9.4% (n = 134) had a urinary iodide concentration of >300 MUg/L, indicating the coexistence of excessive iodine intake (EII). The mean TSH was 1.0 +/- 0.6 mIU/L. The body mass index category "overweight/obesity" was a protective factor against EII (odds ratio [OR] = 0.64 [confidence interval (CI) 0.4-1.0]; p = 0.07). Urban areas (73%) had a mean UIC of 213.1 +/- 80 MUg/L compared with 176.8 +/- 76.1 MUg/L in rural areas. The risk for EII increased in children living in a house with more than six people (OR = 1.62 [CI 0.9-2.6]; p < 0.05) and water consumption from shallow wells (OR = 1.70 [CI 0.9-3.1]; p = 0.09). The risk of ID was increased by 70% in schoolchildren who had moderate or severe food insecurity (OR = 1.70 [CI 0.9-3.0]; p > 0.05). CONCLUSION: A significant proportion of schoolchildren still have ID or EII in the northeast region of Brazil, emphasizing the importance of committed public policies to address this problem. Socioeconomic factors and the lack of education about nutritional importance of iodine were important influencing factors in the presence of ID in schoolchildren. PMID- 27184191 TI - Resuspension and atmospheric transport of radionuclides due to wildfires near the Chernobyl Nuclear Power Plant in 2015: An impact assessment. AB - In April and August 2015, two major fires in the Chernobyl Exclusion Zone (CEZ) caused concerns about the secondary radioactive contamination that might have spread over Europe. The present paper assessed, for the first time, the impact of these fires over Europe. About 10.9 TBq of (137)Cs, 1.5 TBq of (90)Sr, 7.8 GBq of (238)Pu, 6.3 GBq of (239)Pu, 9.4 GBq of (240)Pu and 29.7 GBq of (241)Am were released from both fire events corresponding to a serious event. The more labile elements escaped easier from the CEZ, whereas the larger refractory particles were removed more efficiently from the atmosphere mainly affecting the CEZ and its vicinity. During the spring 2015 fires, about 93% of the labile and 97% of the refractory particles ended in Eastern European countries. Similarly, during the summer 2015 fires, about 75% of the labile and 59% of the refractory radionuclides were exported from the CEZ with the majority depositing in Belarus and Russia. Effective doses were above 1 mSv y(-1) in the CEZ, but much lower in the rest of Europe contributing an additional dose to the Eastern European population, which is far below a dose from a medical X-ray. PMID- 27184192 TI - Characterization of a genetically heterogeneous porcine rotavirus C, and other viruses present in the fecal virome of a non-diarrheic Belgian piglet. AB - Next-generation sequencing (NGS) technologies are becoming increasingly accessible, leading to an expanded interest in the composition of the porcine enteric virome. In the present study, the fecal virome of a non-diarrheic Belgian piglet was determined. Although the virome of only a single piglet was analyzed, some interesting data were obtained, including the second complete genome of a pig group C rotavirus (RVC). This Belgian strain was only distantly related to the only other completely characterized pig RVC strain, Cowden. Its relatedness to RVC strains from other host species was also analyzed and the porcine strain found in our study was only distantly related to RVCs detected in humans and cows. The gene encoding the outer capsid protein VP7 belonged to the rare porcine G3 genotype, which might be serologically distinct from most other pig RVC strains. A putative novel RVC VP6 genotype was identified as well. A group A rotavirus strain also present in this fecal sample contained the rare pig genotype combination G11P[27], but was only partially characterized. Typical pig RVA genotypes I5, A8, and T7 were found for the viral proteins VP6, NSP1, and NSP3, respectively. Interestingly, the fecal virome of the piglet also contained an astrovirus and an enterovirus, of which the complete genomes were characterized. Results of the current study indicate that many viruses may be present simultaneously in fecal samples of non-diarrheic piglets. In this study, these viruses could not be directly associated with any disease, but still they might have had a potential subclinical impact on pig growth performance. The fast evolution of NGS will be a powerful tool for future diagnostics in veterinary practice. Its application will certainly lead to better insights into the relevance of many (sub)clinical enteric viral infections, that may have remained unnoticed using traditional diagnostic techniques. This will stimulate the development of new and durable prophylactic measures to improve pig health and production. PMID- 27184193 TI - Mastery motivation in children with complex communication needs: longitudinal data analysis. AB - This study compared longitudinal changes in mastery motivation during parent child free play for 37 children with complex communication needs. Mastery motivation manifests as a willingness to work hard at tasks that are challenging, which is an important quality to overcoming the challenges involved in successful expressive communication using AAC. Unprompted parent-child play episodes were identified in three assessment sessions over an 18-month period and coded for nine categories of mastery motivation in social and object play. All of the object-oriented mastery motivation categories and one social mastery motivation category showed an influence of motor skills after controlling for receptive language. Object play elicited significantly more of all of the object-focused mastery motivation categories than social play, and social play elicited more of one type of social-focused mastery motivation behavior than object play. Mastery motivation variables did not differ significantly over time for children. Potential physical and interpersonal influences on mastery motivation for parents and children with complex communication needs are discussed, including broadening the procedures and definitions of mastery motivation beyond object-oriented measurements for children with complex communication needs. PMID- 27184195 TI - The influence of nanotexturing of poly(lactic-co-glycolic acid) films upon human ovarian cancer cell attachment. AB - In this study, we have produced nanotextured poly(lactic-co-glycolic acid) (PLGA) films by using polystyrene (PS) particles as a template to make a polydimethylsiloxane mould against which PLGA is solvent cast. Biocompatible, biodegradable and nanotextured PLGA films were prepared with PS particles of diameter of 57, 99, 210, and 280 nm that produced domes of the same dimension in the PLGA surface. The effect of the particulate monolayer templating method was investigated to enable preparation of the films with uniformly ordered surface nanodomes. Cell attachment of a human ovarian cancer cell line (OVCAR3) alone and co-cultured with mesenchymal stem cells (MSCs) was evaluated on flat and topographically nano-patterned surfaces. Cell numbers were observed to increase on the nanotextured surfaces compared to non-textured surfaces both with OVCAR3 cultures and OVCAR3-MSC co-cultures at 24 and 48 h time points. PMID- 27184194 TI - High-performance flexible energy storage and harvesting system for wearable electronics. AB - This paper reports on the design and operation of a flexible power source integrating a lithium ion battery and amorphous silicon solar module, optimized to supply power to a wearable health monitoring device. The battery consists of printed anode and cathode layers based on graphite and lithium cobalt oxide, respectively, on thin flexible current collectors. It displays energy density of 6.98 mWh/cm(2) and demonstrates capacity retention of 90% at 3C discharge rate and ~99% under 100 charge/discharge cycles and 600 cycles of mechanical flexing. A solar module with appropriate voltage and dimensions is used to charge the battery under both full sun and indoor illumination conditions, and the addition of the solar module is shown to extend the battery lifetime between charging cycles while powering a load. Furthermore, we show that by selecting the appropriate load duty cycle, the average load current can be matched to the solar module current and the battery can be maintained at a constant state of charge. Finally, the battery is used to power a pulse oximeter, demonstrating its effectiveness as a power source for wearable medical devices. PMID- 27184197 TI - Choledochoscopic lithotripsy is a useful adjunct to laparoscopic common bile duct exploration for hepatolithiasis: a cohort study. AB - BACKGROUND: This study aims to investigate the role of combining choledochoscopic lithotripsy with laparoscopic common bile duct exploration for hepatolithiasis in patients who are not suitable for hepatectomy. METHODS: From March 2009 to March 2013, 86 patients with hepatolithiasis irrespective of whether they underwent a choledochoscopic plasma shock wave lithotripsy or not were analyzed. RESULTS: Sixty-two patients underwent lithotripsy and 24 patients underwent basket lithoextraction intraoperatively. Plasma shock wave lithotripsy did not lengthen the operating time, but decreased the postoperative residual stone rate and reduced the frequency of postoperative choledochoscopic lithotomy for patients with remnant stones. The overall final stone clearance rate was 98.8%. During a mean follow-up of 26.2 months, recurrent stones and cholangiocarcinoma developed in 1 patient, respectively. CONCLUSION: Laparoscopic common bile duct exploration combined with choledochoscopic lithotripsy is a definitive procedure for hepatolithiasis in patients who are not candidates for hepatectomy. PMID- 27184200 TI - Erratum to "Conditional N-WASP knockout in mouse brain implicates actin cytoskeleton regulation in hydrocephalus pathology"[Experimental Neurology (2014) 29-40]. PMID- 27184199 TI - A rhinitis phenotype associated with increased development of bronchial hyperresponsiveness and asthma in children. AB - BACKGROUND: Allergic rhinitis (AR) has a wide range of clinical features and may be accompanied by comorbid allergic diseases. OBJECTIVE: To identify rhinitis phenotypes in school aged children and to predict the prognosis for developing bronchial hyperresponsiveness (BHR) and asthma. METHODS: This prospective follow up study involved schoolchildren from the Children's Health and Environment Research cohort with current rhinitis, which was defined based on parental reported, physician-diagnosed rhinitis and symptoms of rhinitis in the previous 12 months. All participants were followed up at 2 and 4 years later. Rhinitis clusters were identified by latent class analysis that used demographic, clinical, and environmental variables. RESULTS: In 512 eligible children (age range, 6-8 years), 4 rhinitis phenotypes were identified: cluster 1 (25% of children) was associated with nonatopy and a low socioeconomic status; cluster 2 (36%) was associated with a high-atopic burden but normal lung function; cluster 3 (22%) was associated with a high-atopic burden and impaired lung function; and cluster 4 (17%) was associated with low atopy and a high socioeconomic status. Cluster 3 was associated with the highest total serum IgE levels and blood eosinophil percentages at enrollment and the highest incidence of new cases of BHR (P = .04) and asthma symptoms (P = .005) during follow-up. CONCLUSION: The rhinitis cluster of schoolchildren with atopy and impaired lung function is associated with allergic march. This identification of distinct rhinitis phenotypes in affected children may help to prevent allergic march in children with rhinitis. PMID- 27184196 TI - Glucocorticoid Receptor-Targeted Liposomal Codelivery of Lipophilic Drug and Anti Hsp90 Gene: Strategy to Induce Drug-Sensitivity, EMT-Reversal, and Reduced Malignancy in Aggressive Tumors. AB - Many cancers including the late stage ones become drug-resistant and undergo epithelial-to-mesenchymal transition (EMT). These lead to enhanced invasion, migration, and metastasis toward manifesting its aggressiveness and malignancy. One of the key hallmarks of cancer is its overdependence on glycolysis as its preferred energy metabolism pathway. The strict avoidance of alternate energy pathway gluconeogenesis by cancer cells points to a yet-to-be hoisted role of glucocorticoid receptor (GR) especially in tumor microenvironment, where cells are known to become drug-sensitive through induction of gluconeogenesis. However, since GR is involved in metabolism, anti-inflammatory reactions, immunity besides inducing gluconeogenesis, a greater role of GR in tumor microenvironment is envisaged. We have shown previously that GR, although ubiquitously expressed in all cells; afford to be an effective cytoplasmic target for killing cancer cells selectively. Herein, we report the therapeutic use of a newly developed GR targeted liposomal concoction (DXE) coformulating a lipophilic drug (ESC8) and an anti-Hsp90 anticancer gene against aggressive tumor models. This induced drug sensitivity and apoptosis while reversing EMT in tumor cells toward effective retardation of aggressive growth in pancreas and skin tumor models. Additionally, the ESC8-free lipid formulation upon cotreatment with hydrophilic drugs, gemcitabine and doxorubicin, could effectively sensitize and kill pancreatic cancer and melanoma cells, respectively. The formulation-triggered EMT-reversal was GR-dependent. Overall, we found a new strategy for drug sensitization that led to the advent of new GR-targeted anticancer therapeutics. PMID- 27184198 TI - Parental timing of allergenic food introduction in urban and suburban populations. AB - BACKGROUND: Recommendations on timing for introduction of allergenic foods in an infant diet have changed twice during the past decade. How families with different demographic characteristics implement the change has not been studied in the United States. OBJECTIVE: To compare the age of introduction of allergenic foods between an urban Medicaid-based population and a suburban private insurance based population in Cincinnati, Ohio. METHODS: Two hundred parent surveys were distributed at well-child checkups between 4 and 36 months of age. Data were analyzed using distribution mapping to determine the difference in the age of introduction of infant formula, infant solids, whole cow's milk, eggs, peanut, and fish. Random forest analysis was used to determine the most important factors affecting the age of introduction for both populations. RESULTS: There was no statistically significant difference in the age of infant solid introduction, but urban populations introduced allergenic foods earlier than suburban populations, with a statistically significant difference in the age of introduction of infant formula, whole cow's milk, eggs, peanut, and fish. The most important factor for the timing of all food introductions was the recommended age of introduction from health care professionals. CONCLUSION: There is a difference between urban and suburban populations in the timing of introduction of allergenic foods but not in other infant solid foods. The reliance on physician recommendation for both populations supports the need for education and guidance to health care professionals on up-to-date guidance and recommendations. PMID- 27184201 TI - Neural sensitivity to syllable frequency and mutual information in speech perception and production. AB - Many factors affect our ability to decode the speech signal, including its quality, the complexity of the elements that compose it, as well as their frequency of occurrence and co-occurrence in a language. Syllable frequency effects have been described in the behavioral literature, including facilitatory effects during speech production and inhibitory effects during word recognition, but the neural mechanisms underlying these effects remain largely unknown. The objective of this study was to examine, using functional neuroimaging, the neurobiological correlates of three different distributional statistics in simple 2-syllable nonwords: the frequency of the first and second syllables, and the mutual information between the syllables. We examined these statistics during nonword perception and production using a powerful single-trial analytical approach. We found that repetition accuracy was higher for nonwords in which the frequency of the first syllable was high. In addition, brain responses to distributional statistics were widespread and almost exclusively cortical. Importantly, brain activity was modulated in a distinct manner for each statistic, with the strongest facilitatory effects associated with the frequency of the first syllable and mutual information. These findings show that distributional statistics modulate nonword perception and production. We discuss the common and unique impact of each distributional statistic on brain activity, as well as task differences. PMID- 27184202 TI - NEOCIVET: Towards accurate morphometry of neonatal gyrification and clinical applications in preterm newborns. AB - Cerebral cortical folding becomes dramatically more complex in the fetal brain during the 3rd trimester of gestation; the process continues in a similar fashion in children who are born prematurely. To quantify this morphological development, it is necessary to extract the interface between gray matter and white matter, which is particularly challenging due to changing tissue contrast during brain maturation. We employed the well-established CIVET pipeline to extract this cortical surface, with point correspondence across subjects, using a surface based spherical registration. We then developed a variant of the pipeline, called NEOCIVET, that quantified cortical folding using mean curvature and sulcal depth while addressing the well-known problems of poor and temporally-varying gray/white contrast as well as motion artifact in neonatal MRI. NEOCIVET includes: i) a tissue classification technique that analyzed multi-atlas texture patches using the nonlocal mean estimator and subsequently applied a label fusion approach based on a joint probability between templates, ii) neonatal template construction based on age-specific sub-groups, and iii) masking of non interesting structures using label-fusion approaches. These techniques replaced modules that might be suboptimal for regional analysis of poor-contrast neonatal cortex. The proposed segmentation method showed more accurate results in subjects with various ages and with various degrees of motion compared to state-of-the-art methods. In the analysis of 158 preterm-born neonates, many with multiple scans (n=231; 26-40weeks postmenstrual age at scan), NEOCIVET identified increases in cortical folding over time in numerous cortical regions (mean curvature: +0.003/week; sulcal depth: +0.04mm/week) while folding did not change in major sulci that are known to develop early (corrected p<0.05). The proposed pipeline successfully mapped cortical structural development, supporting current models of cerebral morphogenesis, and furthermore, revealed impairment of cortical folding in extremely preterm newborns relative to relatively late preterm newborns, demonstrating its potential to provide biomarkers of prematurity-related developmental outcome. PMID- 27184204 TI - Dissociable brain biomarkers of fluid intelligence. AB - Cognitive neuroscience has long sought to understand the biological foundations of human intelligence. Decades of research have revealed that general intelligence is correlated with two brain-based biomarkers: the concentration of the brain biochemical N-acetyl aspartate (NAA) measured by proton magnetic resonance spectroscopy (MRS) and total brain volume measured using structural MR imaging (MRI). However, the relative contribution of these biomarkers in predicting performance on core facets of human intelligence remains to be well characterized. In the present study, we sought to elucidate the role of NAA and brain volume in predicting fluid intelligence (Gf). Three canonical tests of Gf (BOMAT, Number Series, and Letter Sets) and three working memory tasks (Reading, Rotation, and Symmetry span tasks) were administered to a large sample of healthy adults (n=211). We conducted exploratory factor analysis to investigate the factor structure underlying Gf independent from working memory and observed two Gf components (verbal/spatial and quantitative reasoning) and one working memory component. Our findings revealed a dissociation between two brain biomarkers of Gf (controlling for age and sex): NAA concentration correlated with verbal/spatial reasoning, whereas brain volume correlated with quantitative reasoning and working memory. A follow-up analysis revealed that this pattern of findings is observed for males and females when analyzed separately. Our results provide novel evidence that distinct brain biomarkers are associated with specific facets of human intelligence, demonstrating that NAA and brain volume are independent predictors of verbal/spatial and quantitative facets of Gf. PMID- 27184203 TI - Consistent cortical reconstruction and multi-atlas brain segmentation. AB - Whole brain segmentation and cortical surface reconstruction are two essential techniques for investigating the human brain. Spatial inconsistences, which can hinder further integrated analyses of brain structure, can result due to these two tasks typically being conducted independently of each other. FreeSurfer obtains self-consistent whole brain segmentations and cortical surfaces. It starts with subcortical segmentation, then carries out cortical surface reconstruction, and ends with cortical segmentation and labeling. However, this "segmentation to surface to parcellation" strategy has shown limitations in various cohorts such as older populations with large ventricles. In this work, we propose a novel "multi-atlas segmentation to surface" method called Multi-atlas CRUISE (MaCRUISE), which achieves self-consistent whole brain segmentations and cortical surfaces by combining multi-atlas segmentation with the cortical reconstruction method CRUISE. A modification called MaCRUISE(+) is designed to perform well when white matter lesions are present. Comparing to the benchmarks CRUISE and FreeSurfer, the surface accuracy of MaCRUISE and MaCRUISE(+) is validated using two independent datasets with expertly placed cortical landmarks. A third independent dataset with expertly delineated volumetric labels is employed to compare segmentation performance. Finally, 200MR volumetric images from an older adult sample are used to assess the robustness of MaCRUISE and FreeSurfer. The advantages of MaCRUISE are: (1) MaCRUISE constructs self consistent voxelwise segmentations and cortical surfaces, while MaCRUISE(+) is robust to white matter pathology. (2) MaCRUISE achieves more accurate whole brain segmentations than independently conducting the multi-atlas segmentation. (3) MaCRUISE is comparable in accuracy to FreeSurfer (when FreeSurfer does not exhibit global failures) while achieving greater robustness across an older adult population. MaCRUISE has been made freely available in open source. PMID- 27184205 TI - Source-specific workplace social support and high-sensitivity C-reactive protein levels among Japanese workers: A 1-year prospective cohort study. AB - BACKGROUND: This study investigated the prospective association between source specific workplace social support and high-sensitivity C-reactive protein (hs CRP) levels in workers in Japan. METHODS: We conducted a 1-year prospective cohort study with 1,487 men and 533 women aged 18-65 years. Participants worked at two manufacturing worksites in Japan and were free of major illness. We used multivariable linear regression analyses to evaluate the prospective association between supervisor and coworker support at baseline, and hs-CRP levels at follow up. We conducted the analyses separately for men and women. RESULTS: For women, high supervisor support at baseline was significantly associated with lower hs CRP levels at follow-up (beta = -0.109, P < 0.01), whereas coworker support at baseline was not significantly associated with hs-CRP levels at follow-up. Associations between supervisor and coworker support and hs-CRP levels were not significant for men. CONCLUSIONS: Supervisor support may have beneficial effects on inflammatory markers in working women. Am. J. Ind. Med. 59:676-684, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27184207 TI - APIC position paper: Safe injection, infusion, and medication vial practices in health care. AB - The transmission of bloodborne viruses and other microbial pathogens to patients during routine health care procedures continues to occur because of the use of improper injection, infusion, medication vial, and point-of-care testing practices by health care personnel. These unsafe practices occur in various clinical settings and result in unacceptable and devastating events for patients. This document updates the Association for Professionals in Infection Control and Epidemiology 2010 position paper on safe injection, infusion, and medication vial practices in health care. PMID- 27184206 TI - Telomere length reveals cumulative individual and transgenerational inbreeding effects in a passerine bird. AB - Inbreeding results in more homozygous offspring that should suffer reduced fitness, but it can be difficult to quantify these costs for several reasons. First, inbreeding depression may vary with ecological or physiological stress and only be detectable over long time periods. Second, parental homozygosity may indirectly affect offspring fitness, thus confounding analyses that consider offspring homozygosity alone. Finally, measurement of inbreeding coefficients, survival and reproductive success may often be too crude to detect inbreeding costs in wild populations. Telomere length provides a more precise measure of somatic costs, predicts survival in many species and should reflect differences in somatic condition that result from varying ability to cope with environmental stressors. We studied relative telomere length in a wild population of Seychelles warblers (Acrocephalus sechellensis) to assess the lifelong relationship between individual homozygosity, which reflects genome-wide inbreeding in this species, and telomere length. In juveniles, individual homozygosity was negatively associated with telomere length in poor seasons. In adults, individual homozygosity was consistently negatively related to telomere length, suggesting the accumulation of inbreeding depression during life. Maternal homozygosity also negatively predicted offspring telomere length. Our results show that somatic inbreeding costs are environmentally dependent at certain life stages but may accumulate throughout life. PMID- 27184209 TI - Factors associated with the receipt of antimicrobials among chronic hemodialysis patients. AB - BACKGROUND: Antimicrobial use is common among patients receiving chronic hemodialysis (CHD) and may represent an important antimicrobial stewardship opportunity. The objective of this study is to characterize CHD patients at increased risk of receiving antimicrobials, including not indicated antimicrobials. METHODS: We conducted a prospective cohort study over a 12-month period among patients receiving CHD in 2 outpatient dialysis units. Each parenteral antimicrobial dose administered was characterized as indicated or not indicated based on national guidelines. Patient factors associated with receipt of antimicrobials and receipt of >=1 inappropriate antimicrobial dose were analyzed. RESULTS: A total of 89 of 278 CHD patients (32%) received >=1 antimicrobial doses and 52 (58%) received >=1 inappropriately indicated dose. Patients with tunneled catheter access, a history of colonization or infection with a multidrug-resistant organism, and receiving CHD sessions during daytime shifts were more likely to receive antimicrobials (odds ratio [OR], 5.16; 95% confidence interval [CI], 2.72-9.80; OR, 5.43; 95% CI, 1.84-16.06; OR, 4.59; 95% CI, 1.20-17.52, respectively). Patients with tunneled catheter access, receiving CHD at dialysis unit B, and with a longer duration of CHD prior to enrollment were at higher risk of receiving an inappropriately indicated antimicrobial dose (incidence rate ratio, 2.23; 95% CI, 1.16-4.29; incidence rate ratio, 2.67; 95% CI, 1.34-5.35; incidence rate ratio, 1.11; 95% CI, 1.01-1.23, respectively). CONCLUSIONS: This study of all types of antimicrobials administered in 2 outpatient dialysis units identified several important factors to consider when developing antimicrobial stewardship programs in this health care setting. PMID- 27184208 TI - Using the Comprehensive Unit-based Safety Program model for sustained reduction in hospital infections. AB - BACKGROUND: Prompted by the high number of central line-associated bloodstream infections (CLABSIs), our institution joined the national On the CUSP: Stop BSI initiative. We not only report the significant impact that the Comprehensive Unit based Safety Program (CUSP) had in reducing CLABSI, but also report catheter associated urinary tract infections (CAUTIs) and ventilator-associated pneumonia (VAP) in 2 intensive care units (ICUs). METHODS: At our community-based academic health care system, 2 ICUs implemented CUSP tools and developed local interventions to reduce CLABSI and other safety problems. We measured CLABSI, CAUTI, and VAP during baseline, the CUSP period, and a post-CUSP period. RESULTS: CLABSIs decreased from 3.9 per 1,000 catheter days at baseline to 1.2 during the CUSP period to 0.6 during the post-CUSP period (rate ratio, 0.16; 95% confidence interval [CI], 0.07-0.35). CAUTIs decreased from 2.4 per 1,000 patient days to 1.2 during the post-CUSP period (rate ratio, 0.4; 95% CI, 0.24-0.65). VAP rate decreased from 2.7 per 1,000 ventilator days to 1.6 during the CUSP and post-CUSP periods (rate ratio, 0.58; 95% CI, 0.30-1.10). Device utilization decreased significantly in both ICUs. CONCLUSIONS: Implementation of CUSP was associated with significant decreases in CLABSI, CAUTI, and VAP. The CUSP model, allowing for implementation of evidence-based practices and engagement of frontline staff, creates sustainable improvements that reach far beyond the initial targeted problem. PMID- 27184210 TI - Underdetection and underreporting of pertussis in children attended in primary health care centers: Do surveillance systems require improvement? AB - BACKGROUND: Pertussis is an underestimated disease. Several European countries have developed models to account for underreporting of pertussis. The aim of this study was to estimate pertussis underdetection and underreporting in pediatric patients attending primary health care centers (PHCCs). METHODS: We reviewed clinical records of PHCCs in Barcelona in 2012. Factors associated with underdetection and underreporting were analyzed by logistic regression. Adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: We included 3,505 children aged < 7 years (mean age, 34 +/- 20.7 months; range, 0-82 months) presenting with cough; 9.3% (326 out of 3,505) of patients also had >= 1 symptoms related to pertussis accompanied by cough for a duration >= 2 weeks. Of the 326 children receiving clinical criteria, only 31 (9.5%) were laboratory-confirmed and 6 (1.8%) were detected but not reported. There were 295 (90.5%) undetected suspected pertussis cases. Age >= 18 months (aOR, 8.51; 95% CI, 1.82-39.86), cyanosis (aOR, 6.71; 95% CI, 1.43-31.39), request for chest radiograph (aOR, 0.26; 95% CI, 0.07-0.99), and request for other laboratory tests (aOR, 5.39; 95% CI, 2.19-13.27) were associated with underdetection. Paroxysmal cough (aOR, 5.77; 95% CI, 1.05-31.76) and request for other laboratory tests (aOR, 2.91; 95% CI, 1.11-7.62) were associated with underreporting. CONCLUSIONS: Both underdetection and underreporting complicate the understanding of pertussis epidemiology. Correct assessment of pertussis symptoms and notification of cases must be improved to control pertussis. PMID- 27184211 TI - Whole exome sequencing in congenital pain insensitivity identifies a novel causative intronic NTRK1-mutation due to uniparental disomy. AB - Congenital insensitivity to pain and anhidrosis (CIPA), also known as hereditary sensory and autonomic neuropathy type IV (HSAN IV), is characterized by recurrent episodes of unexplained high fever, loss of pain perception and temperature sensation, absent sweating, repeated traumatic and thermal injuries, and mild mental retardation. After exclusion of obviously pathogenic mutations in NTRK1, the most common cause of CIPA, whole exome sequencing (WES) was carried out in a CIPA patient with unrelated parents. No mutations in known HSAN genes were identified. However, filtering for genes carrying two rare sequence variations detected 13 homozygous single nucleotide variants (SNV), all being located on chromosome 1. Further analysis strongly suggested that this finding might be best explained by uniparental disomy of chromosome 1. Because NTRK1 is also located on chromosome 1, we re-evaluated WES data and detected a novel intronic sequence variation at position c.2188-12 C>A, homozygously because of uniparental disomy. Subsequent analysis of NTRK1 transcripts in peripheral blood cells of the patient revealed an influence of the variant on mRNA splicing. The C>A transversion generated a novel splice-site, which led to the incorporation of 10 intronic bases into the NTRK1 mRNA and consequently to a non-functional gene product. (c) 2016 Wiley Periodicals, Inc. PMID- 27184212 TI - Training residents to be factually accurate and articulate: A case study using foetal heart rate monitoring nomenclature. AB - Careful communication between members of the obstetric team about intrapartum foetal heart rate is critical for clinical management and patient safety. This study evaluated the benefits of two testing modalities in assessing resident physician knowledge of the 2008 NICHD nomenclature. Multiple-choice (MC) and short-answer (SA) examinations were administered to Obstetrics and Gynecology resident physicians before an educational intervention and then immediately after the training, at 6 months and at 12 months. Test scores on both the MC and the SA examinations improved after the training session. The improvement was sustained over the course of the study. Residents performed higher on the MC examination than on the SA test. This study suggests that formalised teaching in foetal heart rate monitoring improves resident physician knowledge of the NICHD nomenclature and that SA examinations may better discriminate between residents who are and are not able to accurately articulate foetal heart rate monitoring terminology. PMID- 27184213 TI - Aqueous Copper(II) Photoinduced Polymerization of Acrylates: Low Copper Concentration and the Importance of Sodium Halide Salts. AB - Photoinduced metal-mediated radical polymerization is a rapidly developing technique which allows for the synthesis of macromolecules with defined molecular weight and narrow molecular weight distributions, although typically exhibiting significant limitations in aqueous media. Herein we demonstrate that the presence of alkali metal halide salts, in conjunction with low copper concentration and UV irradiation, allows for the controlled polymerization of water-soluble acrylates in aqueous media, yielding narrow molecular weight distributions and high conversions. Despite the aqueous environment which typically compromises polymer end group fidelity, chain extensions have also been successfully performed and different degrees of polymerization were targeted. Importantly, no conversion was observed in the absence of UV light and the polymerization could be switched "on" and "off" upon demand, as demonstrated by intermittent light and dark periods and thus allowing access to spatiotemporal control. PMID- 27184214 TI - A Stochastic Hill Climbing Approach for Simultaneous 2D Alignment and Clustering of Cryogenic Electron Microscopy Images. AB - A critical step in the analysis of novel cryogenic electron microscopy (cryo-EM) single-particle datasets is the identification of homogeneous subsets of images. Methods for solving this problem are important for data quality assessment, ab initio 3D reconstruction, and analysis of population diversity due to the heterogeneous nature of macromolecules. Here we formulate a stochastic algorithm for identification of homogeneous subsets of images. The purpose of the method is to generate improved 2D class averages that can be used to produce a reliable 3D starting model in a rapid and unbiased fashion. We show that our method overcomes inherent limitations of widely used clustering approaches and proceed to test the approach on six publicly available experimental cryo-EM datasets. We conclude that, in each instance, ab initio 3D reconstructions of quality suitable for initialization of high-resolution refinement are produced from the cluster centers. PMID- 27184215 TI - Analysis of occupational health hazards and associated risks in fuzzy environment: a case research in an Indian underground coal mine. AB - This paper presents a unique hierarchical structure on various occupational health hazards including physical, chemical, biological, ergonomic and psychosocial hazards, and associated adverse consequences in relation to an underground coal mine. The study proposes a systematic health hazard risk assessment methodology for estimating extent of hazard risk using three important measuring parameters: consequence of exposure, period of exposure and probability of exposure. An improved decision making method using fuzzy set theory has been attempted herein for converting linguistic data into numeric risk ratings. The concept of 'centre of area' method for generalized triangular fuzzy numbers has been explored to quantify the 'degree of hazard risk' in terms of crisp ratings. Finally, a logical framework for categorizing health hazards into different risk levels has been constructed on the basis of distinguished ranges of evaluated risk ratings (crisp). Subsequently, an action requirement plan has been suggested, which could provide guideline to the managers for successfully managing health hazard risks in the context of underground coal mining exercise. PMID- 27184216 TI - Strong, Twist-Stable Carbon Nanotube Yarns and Muscles by Tension Annealing at Extreme Temperatures. AB - A high-speed incandescent tension annealing process (ITAP) is used to increase the modulus and strength of twist-spun carbon nanotube yarns by up to 12-fold and 2.6-fold, respectively, provide remarkable resistance to oxidation and powerful protonating acids, and freeze yarn untwist. This twist stability enables torsional artificial-muscle motors having improved performance and minimizes problematic untwist during weaving nanotube yarns. PMID- 27184217 TI - Depoliticising the political: Market solutions and the retreat of Swedish institutional drug treatment from state management. AB - BACKGROUND: This article examines developments in the Swedish drug treatment services in 1982-2000 and explores the ways in which political initiatives and the state administration's management have contributed to the major privatisations of institutional drug treatment during this period. METHODS: The empirical basis for the textual analysis lies in official reports, parliamentary material and archived records from the Stockholm County Administrative Board's management of treatment facilities. RESULTS: The major privatisations of drug treatment services in the 1980s were both unintentional and unwanted and mainly arose from a lack of bureaucratic control and ideological anchorage. The privatisations were, however, reinforced by ideologically driven NPM-oriented political initiatives in the 1990s. CONCLUSION: The market-oriented treatment services have failed to fulfil the needs for diversity and availability within a publicly financed sector, which deals with unevenly informed and often socio economically weak citizens. New management models in this field must ensure that ideological considerations are taken into account to meet politically decided goals and means. PMID- 27184218 TI - The users of Novel Psychoactive Substances: Online survey about their characteristics, attitudes and motivations. AB - BACKGROUND: The increasing number of Novel Psychoactive Substances (NPS) constitutes a challenge for public health agencies and researchers worldwide. Scientific studies about NPS and their users are limited and there is a need to explore the general motivations for NPS use but also to examine if and how the motivations differ between substances from separate effect classes. The aim of the present study was to investigate the characteristics, including attitudes and motivations, of a self-selected sample of international NPS users. METHODS: An online survey containing questions about drug use history, attitudes, motivations for use, and WHO-5 Wellbeing Index was promoted at the drug discussion forum bluelight.org. The data was analysed using SPSS. RESULTS: The sample consisted of 619 international NPS users with overall good emotional well-being despite extensive experience of both traditional and novel drugs. The main incentive for use of NPS in general was pleasure and enjoyment. However, going beyond the general approach to NPS revealed significant variations between drug groups. For example, the use of hallucinogens was substantially motivated by self-exploration and spiritual attainment and showed very low levels of addiction potential while the use of opioids and especially GABA activating substances was mainly motivated by coping and showed much higher levels of addiction potential. Synthetic cannabinoids were the least appreciated and least likely to be used again, and were mainly motivated by circumstances such as availability and legality. CONCLUSION: Understanding the different motivations for NPS use in terms of drug groups could enable more effective prevention and consequently a reduction in harm. PMID- 27184220 TI - ERRATUM. PMID- 27184219 TI - Benefits of short educational programmes in preventing drink-driving recidivism: A ten-year follow-up randomised controlled trial. AB - BACKGROUND: One fifth of drivers convicted of drink-driving for the first time will be convicted again for the same offence in subsequent years. Lecture-based educational programmes are believed to reduce recidivism. Little is known about the modalities of enhancing the benefits of such programs. METHODS: This parallel randomised controlled trial measured the effects of the duration of lectures and the presence of a close relative 'in class' on rates of recidivism during the ten years following an initial drink-driving conviction. Of 1588 drivers in the Canton of Geneva convicted of a first-time offence with a blood alcohol concentration (BAC) of between 0.80 and 2.49g/kg from May 2001 to February 2004, 727 agreed to participate and were randomly assigned to either a seven-hour series of lectures, a four-hour series with a friend or close relative, or a brief two-hour lecture. Time until recidivism was retrieved from a national registry that contains details of recidivism that took place up to ten years after the first offence. RESULTS: Significant effects of briefer lectures over the standard day-long series of lectures were observed only during the most influential time period with regards to recidivism levels-the two years following the intervention. Replacing the usual one-day series of lectures by briefer two hour lectures would reduce, by 25% (CI95%; 3-44%), the risk of recidivism. CONCLUSION: This study does not support policymakers' decision to rely on a seven hour series of lectures to decrease DUI recidivism. The advantages of shorter lectures over no lecture still need to be evaluated. PMID- 27184221 TI - Loss of RUNX3 expression is an independent adverse prognostic factor in diffuse large B-cell lymphoma. AB - Runt-related transcription factor-3 (RUNX3) is an apoptotic factor correlated with tumorigenesis and cancer progression. Enhancer of zeste homolog-2 (EZH2), a histone methyltransferase, has been shown to mediate silencing of RUNX3. We investigated RUNX3 and EZH2 expression in diffuse large B-cell lymphoma (DLBCL). A chart review was conducted and tissue-microarray (TMA) was constructed using archived tissue from 83 DLBCL cases. RUNX3 and EZH2 protein expression was correlated with immunophenotypic subtypes and survival. Loss of RUNX3 was observed in 20 cases; EZH2 expression was observed in 59 cases. RUNX3-negative tumors had significantly lower overall and recurrence-free survival (log-rank test, p < 0.0001 for each). No correlation was found between RUNX3 and EZH2 staining (r = 0.14; p = 0.2). Results suggest a role for the RUNX3 gene in the pathogenesis of DLBCL. Loss of RUNX3 expression strongly correlated with adverse prognosis, independent of subtype. Further studies are warranted to elucidate the biology and prognostic utility of RUNX3 in DLBCL. PMID- 27184222 TI - Utility of 16S rDNA Sequencing for Identification of Rare Pathogenic Bacteria. AB - BACKGROUND: Phenotypic identification systems are established methods for laboratory identification of bacteria causing human infections. Here, the utility of phenotypic identification systems was compared against 16S rDNA identification method on clinical isolates obtained during a 5-year study period, with special emphasis on isolates that gave unsatisfactory identification. METHODS: One hundred and eighty-seven clinical bacteria isolates were tested with commercial phenotypic identification systems and 16S rDNA sequencing. Isolate identities determined using phenotypic identification systems and 16S rDNA sequencing were compared for similarity at genus and species level, with 16S rDNA sequencing as the reference method. RESULTS: Phenotypic identification systems identified ~46% (86/187) of the isolates with identity similar to that identified using 16S rDNA sequencing. Approximately 39% (73/187) and ~15% (28/187) of the isolates showed different genus identity and could not be identified using the phenotypic identification systems, respectively. Both methods succeeded in determining the species identities of 55 isolates; however, only ~69% (38/55) of the isolates matched at species level. 16S rDNA sequencing could not determine the species of ~20% (37/187) of the isolates. CONCLUSION: The 16S rDNA sequencing is a useful method over the phenotypic identification systems for the identification of rare and difficult to identify bacteria species. The 16S rDNA sequencing method, however, does have limitation for species-level identification of some bacteria highlighting the need for better bacterial pathogen identification tools. PMID- 27184223 TI - Resistant in-stent restenosis in the drug eluting stent era. AB - BACKGROUND: In the drug eluting stent (DES) era, repeat in-stent restenosis (ISR) of the same coronary lesion, despite percutaneous coronary intervention (PCI), is a rare but challenging problem that has not been reported. We aim to describe what we propose as the occurrence of "resistant"-ISR (R-ISR) in the DES era, including angiographic patterns and outcomes. METHODS: We defined R-ISR as the recurrence of an ISR episode after successful treatment of the same lesion. We identified 276 consecutive patients with 291 lesions who had R-ISR between May 2003 and June 2012. Quantitative coronary angiography (QCA) was performed for the first and second ISR episodes. Outcomes at one year, including death, myocardial infarction (MI), and target lesion failure (TLF), were analyzed. RESULTS: Patients with R-ISR had a high frequency of diabetes (62%), chronic kidney disease (39%), bifurcation lesions (51%), and moderate to severe calcified lesions (52%). The most common pattern of R-ISR was focal (77%). R-ISR lesions were treated with DES implantation (55%) or balloon-only strategy (45%). The mortality rate and TLF at 2-years were 9.3% and 51% respectively. The overall 2 year TLF rate did not vary with the originally implanted stent, angiographic pattern (focal versus diffuse), or revascularization strategy. CONCLUSIONS: R-ISR appears to consist predominantly of focal lesions and occurs in patients at high clinical and angiographic risk, conceivably owing to their unique diabetic and coronary calcification profile. Clinical outcomes are suboptimal irrespective of angiographic pattern or treatment strategy, indicating the recalcitrant nature of the disease, and need for aggressive treatment of cardiovascular risk factors and novel interventional approaches. (c) 2016 Wiley Periodicals, Inc. PMID- 27184226 TI - [Gangrenous ecthyma: Unusual presentation]. PMID- 27184227 TI - [Amelanotic acral melanoma]. PMID- 27184225 TI - Tunable Oxygen Functional Groups as Electrocatalysts on Graphite Felt Surfaces for All-Vanadium Flow Batteries. AB - A dual oxidative approach using O2 plasma followed by treatment with H2 O2 to impart oxygen functional groups onto the surface of a graphite felt electrode. When used as electrodes for an all-vanadium redox flow battery (VRB) system, the energy efficiency of the cell is enhanced by 8.2 % at a current density of 150 mA cm(-2) compared with one oxidized by thermal treatment in air. More importantly, by varying the oxidative techniques, the amount and type of oxygen groups was tailored and their effects were elucidated. It was found that O-C=O groups improve the cells performance whereas the C-O and C=O groups degrade it. The reason for the increased performance was found to be a reduction in the cell overpotential after functionalization of the graphite felt electrode. This work reveals a route for functionalizing carbon electrodes to improve the performance of VRB cells. This approach can lower the cost of VRB cells and pave the way for more commercially viable stationary energy storage systems that can be used for intermittent renewable energy storage. PMID- 27184224 TI - Single dose GLP toxicity and biodistribution study of a conditionally replicative adenovirus vector, CRAd-S-pk7, administered by intracerebral injection to Syrian hamsters. AB - BACKGROUND: CRAd-S-pk7 is a conditionally replicative oncolytic adenoviral vector that contains a survivin promoter and a pk7 fiber modification that confer tumor specific transcriptional targeting and preferential replication in glioma while sparing the surrounding normal brain parenchyma. METHODS: This IND-enabling study performed under GLP conditions evaluated the toxicity and biodistribution of CRAd S-pk7 administered as a single intracerebral dose to Syrian hamsters, a permissive model of adenoviral replication. Two hundred and forty animals were stereotactically administered either vehicle (n = 60) or CRAd-S-pk7 at 2.5 * 10(7), 2.5 * 10(8), or 2.5 * 10(9) viral particles (vp)/animal (each n = 60) on day 1. The animals were closely monitored for toxicology evaluation, assessment of viral distribution, and immunogenicity of CRAd-S-pk7. RESULTS: Changes in hematology, clinical chemistry, and coagulation parameters were minor and transient, and consistent with the inflammatory changes observed microscopically. These changes were considered to be of little toxicological significance. The vector remained localized primarily in the brain and to some degree in the tissues at the incision site. Low levels of vector DNA were detected in other tissues in a few animals suggesting systemic circulation of the virus. Viral DNA was detected in brains of hamsters for up to 62 days. However, microscopic changes and virus-related toxicity to the central nervous system were considered minor and decreased in incidence and severity over time. Such changes are not uncommon in studies using adenoviral vectors. CONCLUSION: This study provides safety and toxicology data justifying a clinical trial of CRAd-S-pk7 loaded in FDA-approved HB1.F3.CD neural stem cell carriers administered at the tumor resection bed in humans with recurrent malignant glioma. PMID- 27184228 TI - Gaseous NH3 Confers Porous Pt Nanodendrites Assisted by Halides. AB - Tailoring the morphology of Pt nanocrystals (NCs) is of great concern for their enhancement in catalytic activity and durability. In this article, a novel synthetic strategy is developed to selectively prepare porous dendritic Pt NCs with different structures for oxygen reduction reaction (ORR) assisted by NH3 gas and halides (F(-), Cl(-), Br(-)). The NH3 gas plays critical roles on tuning the morphology. Previously, H2 and CO gas are reported to assist the shape control of metallic nanocrystals. This is the first demonstration that NH3 gas assists the Pt anisotropic growth. The halides also play important role in the synthetic strategy to regulate the formation of Pt NCs. As-made porous dendritic Pt NCs, especially when NH4F is used as a regulating reagent, show superior catalytic activity for ORR compared with commercial Pt/C catalyst and other previously reported Pt-based NCs. PMID- 27184234 TI - Blink reflex in subjects with different hypnotizability: New findings for an old debate. AB - Hypnotizability is associated with attentional characteristics whose neurophysiological bases are still under debate. Aim of the study was the assessment of possible hypnotizability-related differences in blink reflex (BR) which has a nociceptive component, is sensitive to attentional-emotional traits and states and is modulated by the brain dopamine content. In 10 high (highs) and 10 low hypnotizable participants (lows) BR was induced by electrical nociceptive stimulation of the right supraorbital nerve in the absence (noW) and in the presence of a visual cue preceding the electrical stimulation by 0.1ms (W01) and by 1ms (W1). The studied variables were: the amplitude of BR components (R1, R2, R3), the amplitude of the quick change (TO) of heart rate ("turbulence") induced by stimulation and its recovery slope (TS), the role of the Behavioral Inhibition/Activation System (BIS/BAS) in the variability BR and cardiac turbulence. Repeated measures ANOVA did not show any significant difference between highs and lows in blink reflex. TO indicated stimulation related HR increase in highs and decrease in lows, TS was larger in highs. BIS and BAS accounted for the warning effects on the BR amplitude and modulated the hypnotizability and warning effects on TO and TS. Findings do not support dopamine based hypnotizability-related attentional abilities. In contrast, they indicate that hypnotizability modulates the short-lasting cardiac response to electrical nociceptive stimulation. PMID- 27184230 TI - Nanoparticle-Aided Amplification of Fluorescence Polarization for Ultrasensitively Monitoring Activity of Telomerase. AB - To realize facile and reliable analyzing telomerase activity in homogeneous, herein, for the first time, a fluorescent polarization (FP) strategy was developed for polymerase chain reaction (PCR) free monitoring activity of human telomerase at single-cell level ground on gold nanoparticle (GNP) enhancement of FP. First, thiolated telomerase substrate (TS) primer is modified to the surface of GNP via Au-S bond. In the presence of telomerase, TS primer was extended via adding hexamer repeats (GGGTTA), leading to the formation of a long elongation DNA. Several short carboxyfluorescein (FAM)-modified complementary DNA (F-cDNA) can hybridize with the hexamer repeats, resulting in a sharp increase in FP value. Because of the GNP enhancement and self-amplification of telomerase, telomerase activity accounting to one HeLa cell can be rapidly detected in homogeneous solution. Telomerase activities of various cell lines were also favorably estimated. Meanwhile, the inhibition efficiency of telomerase inhibitor was studied, which holds great potential in screening telomerase-targeted anticancer drugs as well. So, a facile method was put forward to reliably and ultrasensitively detect telomerase activity. PMID- 27184229 TI - Molecular Subtyping of Serous Ovarian Cancer Based on Multi-omics Data. AB - Classification of ovarian cancer by morphologic features has a limited effect on serous ovarian cancer (SOC) treatment and prognosis. Here, we proposed a new system for SOC subtyping based on the molecular categories from the Cancer Genome Atlas project. We analyzed the DNA methylation, protein, microRNA, and gene expression of 1203 samples from 599 serous ovarian cancer patients. These samples were divided into nine subtypes based on RNA-seq data, and each subtype was found to be associated with the activation and/or suppression of the following four biological processes: immunoactivity, hormone metabolic, mesenchymal development and the MAPK signaling pathway. We also identified four DNA methylation, two protein expression, six microRNA sequencing and four pathway subtypes. By integrating the subtyping results across different omics platforms, we found that most RNA-seq subtypes overlapped with one or two subtypes from other omics data. Our study sheds light on the molecular mechanisms of SOC and provides a new perspective for the more accurate stratification of its subtypes. PMID- 27184235 TI - Prepulse inhibition and latent inhibition deficits in Roman high-avoidance vs. Roman low-avoidance rats: Modeling schizophrenia-related features. AB - The aim of the present study was to obtain further evidence supporting the validity of a new genetically-based rat model for the study of schizophrenia relevant symptoms. The Roman high- (RHA-I) and low-avoidance (RLA-I) inbred rats have been psychogenetically selected for their rapid versus extremely poor acquisition of the two-way avoidance task in the shuttle box and present two well differentiated profiles regarding several traits related to anxiety, impulsivity and sensitivity to (dopaminergic) psychostimulants. In this study we have tested animals from both strains in two behavioral paradigms that are related to schizophrenia, i.e. prepulse inhibition (PPI) and latent inhibition (LI) of fear potentiated startle (FPS). The results show that while RLA-I rats display good PPI and LI to the context, RHA-Is show an impairment of PPI and no sign of an LI effect, which goes in the direction of the results obtained in schizophrenic patients. Therefore, although further behavioral and psychopharmacological work needs to be done, the present findings and previous studies carried out in our laboratory and others allow us to propose the RHA-I rat strain as a putative genetic rat model of differential schizophrenia-related features. PMID- 27184236 TI - Maternal exposure to environmental enrichment before and during gestation influences behaviour of rat offspring in a sex-specific manner. AB - The beneficial effects of Environmental Enrichment (EE) applied immediately after weaning or even in adulthood have been widely demonstrated. Less is known about the possible changes in behaviour and brain development of the progeny following the exposure of dams to EE. In order to further investigate this matter, female rats were reared in EE for 12weeks, from weaning until delivery. After having confirmed the presence of relevant behavioural effects of EE, both control and EE females underwent mating. Maternal behaviour was observed and male and female offspring were then administered a battery of behavioural test at different ages. EE mothers showed a decreased frequency of total nursing and, during the first 2days of lactation, an increase in licking/grooming behaviour. Maternal exposure to EE affected offspring behaviour in a sex-specific manner: social play behaviour and anxiety-like behaviour were increased in males but not in females and learning ability was improved only in females. As a general trend, maternal EE had a marked influence on motility in male and female offspring in both locomotor activity and swimming speed. Overall, this study highlights the importance of environmental stimulation, not only in the animals directly experiencing EE, but for their progeny too, opening the way to new hypothesis on the heritability mechanisms of behavioural traits. PMID- 27184237 TI - Changes in taste preference and steps taken after sleep curtailment. AB - A substantial proportion of the population does not achieve the recommended amount of sleep. Previous work demonstrates that sleep alterations perturb energy balance by disrupting appetite hormones, increasing energy intake, and decreasing physical activity. This study explored the influence of sleep duration on taste perception as well as effects on dietary intake and physical activity. Participants (n=24 habitual short sleepers and n=27 habitual long sleepers, 82.4% female, 88.2% white, 25.2+/-7.7years) completed two randomized taste visits; one following short sleep duration (<=7h) and one following long sleep duration (>7h). Taste perception measures included sweet and salt detection thresholds (ascending 3-alternative, forced-choice method), as well as sweet preference (Monell 2-series, forced-choice, paired-comparison, tracking method). Steps and sleep were tracked via FitBit, an activity monitoring device. Dietary intake was assessed using 24-hour recalls and analyzed using Nutritionist Pro. Habitual long sleepers had a higher sweet taste preference (p=0.042) and took fewer steps (p=0.036) following sleep curtailment compared to the night where they slept >7h but did not experience changes in dietary intake or detection thresholds. Habitual short-sleepers did not experience changes in taste perception, activity, or dietary intake following sleep alteration. Habitual long-sleepers may be at greater risk of gaining weight when typical sleep patterns are disrupted. PMID- 27184238 TI - Adolescent voluntary exercise attenuated hippocampal innate immunity responses and depressive-like behaviors following maternal separation stress in male rats. AB - Early life stressful events have detrimental effects on the brain and behavior, which are associated with the development of depression. Immune-inflammatory responses have been reported to contribute in the pathophysiology of depression. Many studies have reported on the beneficial effects of exercise against stress. However, underlying mechanisms through which exercise exerts its effects were poorly studied. Therefore, it applied maternal separation (MS), as a valid animal model of early-life adversity, in rats from postnatal day (PND) 2 to 14 for 180min per day. At PND 28, male Wistar albino rats were subjected to 5 experimental groups; 1) controls 2) MS rats 3) MS rats treated with fluoxetine 5mg/kg to PND 60, 4) MS rats that were subjected to voluntary running wheel (RW) exercise and 5) MS rats that were subjected to mandatory treadmill (TM) exercise until adulthood. At PND 60, depressive-like behaviors were assessed by using forced swimming test (FST), splash test, and sucrose preference test (SPT). Our results revealed that depressive-like behaviors following MS stress were associated with an increase in expression of toll-like receptor 4 (Tlr-4) and its main signaling protein, Myd88, in the hippocampal formation. Also, we found that voluntary (and not mandatory) physical exercise during adolescence is protected against depressant effects of early-life stress at least partly through mitigating the innate immune responses in the hippocampus. PMID- 27184239 TI - Assessment of reagents for selenocysteine conjugation and the stability of selenocysteine adducts. AB - Conventional antibody-drug conjugates (ADCs) are heterogeneous mixtures that have poor pharmacokinetic properties and decreased efficacy relative to homogenous ADCs. Furthermore, ADCs that are maleimide-based often have inadequate circulatory stability, which can result in premature drug release with consequent off-target toxicities. Selenocysteine-modified antibodies have been developed that allow site-specific antibody conjugation, yielding homogeneous ADCs. Herein, we survey several electrophilic functional groups that react with selenocystine with high efficiency. Several of these result in conjugates with stabilities that are superior to maleimide conjugates. Among these, the allenamide functional group reacts with notably high efficiency, leads to conjugates with remarkable stability, and shows exquisite selectivity for selenocysteine conjugation. PMID- 27184241 TI - Ongoing Discovery of High-Level Disinfection of Endoscope Practices and the Use of Performance Improvement Methodologies to Improve Processes. PMID- 27184242 TI - Assessment of Endoscope Reprocessing Using Peer-to-Peer Assessment Through a Clinical Community. AB - BACKGROUND: Cleaning, disinfection, and sterilization (CDS) of medical devices are intended to help prevent health care-associated infections (HAIs), a significant cause of mortality and morbidity. In February 2013 the Johns Hopkins Health System (JHHS; Baltimore) formed a clinical community of experts and stakeholders--physicians, nurses, administrators, infection control practitioners, risk managers, and regulatory staff--to assess CDS practices across facilities. METHODS: A survey administered to leadership indicated endoscopy areas of risk. An endoscopy tracer tool with eight major performance areas was then created from best practices identified in the literature, regulatory requirements, and national guidelines for endoscope reprocessing. Peer to-peer (P2P) assessments using the tracer tool were performed at five Johns Hopkins Medicine gastrointestinal endoscopy sites (three hospital-based; two freestanding ambulatory surgery centers) selected on the basis of their large procedural volumes and their operational ability to participate in further areas of the project. RESULTS: The P2P assessments revealed that 20 (42%) of the 48 possible criteria had a noted deficiency at one or more sites. Three of the eight major performance areas on the tracer tool had no deficiencies identified at any of the five sites. Deficiencies were mostly minor process improvements, and only one critical process required immediate alteration of practice. Because the assessments were nonpunitive, horizontal communication enabled feedback on process improvements, alternate methods to achieve outcomes, and solutions to common issues. CONCLUSIONS: A nonpunitive and collaborative peer methodology was successful in capturing and sharing best practices in endoscopy areas. Successful replication in other clinical areas can be an effective way to assess CDS processes and facilitate dialogue for improvements. PMID- 27184240 TI - Hypercalcemia due to Milk-Alkali Syndrome and Fracture-Induced Immobilization in an Adolescent Boy with Hypoparathyroidism. AB - BACKGROUND: Hypercalcemia of immobilization, while rare, may occur in adolescent boys after fracture. Although not fully understood, the mechanism appears to be related to bone turnover uncoupling, in part mediated by upregulation of RANKL. Animal studies suggest that parathyroidectomy suppresses RANKL-stimulated osteoclastogenesis in immobilized bone. Thus, immobilization-induced hypercalcemia should be uncommon in patients with hypoparathyroidism. METHODS/RESULTS: We present a 15-year-old boy with well-controlled hypoparathyroidism who developed hypercalcemia and milk-alkali syndrome 5 weeks after sustaining a severe tibia/fibula fracture requiring bedrest. Milk-alkali syndrome (hypercalcemia, alkalosis, and renal insufficiency) results from chronic excessive ingestion of calcium and absorbable alkali. Prior to fracture, our patient had not experienced hypercalcemia despite high doses of supplements, necessary during puberty. Supplements were discontinued and his biochemistries normalized with saline diuresis and a dose of pamidronate. Alkaline phosphatase, which was low at presentation, returned to normal 5 weeks later with remobilization. CONCLUSIONS: Fracture and immobilization caused acute suppression of bone formation with persistent bone resorption in this rapidly growing adolescent; continuation of carbonate-containing calcium supplements resulted in the milk-alkali syndrome. Therefore, close monitoring of serum calcium with adjustments in supplementation are indicated in immobilized patients with hypoparathyroidism. (c) 2016 S. Karger AG, Basel. PMID- 27184243 TI - Implementation of a Front-End Split-Flow Model to Promote Performance in an Urban Academic Emergency Department. AB - BACKGROUND: In an urban academic emergency department (ED), a front-end split flow model, which entailed deployment of an attending-physician intake model, implementation of a 16-bed clinic decision unit, expanded point-of-care (POC) testing, and dedicated ED transportation services, was created. METHODS: A retrospective, observational, pre-post intervention comparison study was conducted at a large academic urban hospital with 74,000 ED annual visits that serves as a Level 2 Trauma Center. The new flow model was implemented in April 2013, coincident with the opening of a new ED space. RESULTS: During the six month pre- (July 2012-December 2012) and postimplementation (July 2013-December 2013) periods, there were 17,307 and 27,443, respectively, walk-in encounters during the intake times. Despite this 59% increase and a 35% increase in overall ED patient census, implementation of the innovative novel process redesign resulted in a clinically meaningful reduction (median minutes pre vs. post and one-year post) in (1) overall length of stay (LOS) for all walk-ins (220 vs. 175 and 140), discharged (216 vs. 170 and 140), and inpatient admissions (249 vs. 217 and 181); (2) door-to-physician time (minutes) (54 vs. 15 and 12); and (3) left without being seen (LWBS) rates (5.5% vs. 0.5% and 0.0%). The left before visit complete (LBVC) rates were 0.8% vs. 1.1% and 0.6%. The average total relative value unit (RVU) per patient discharged from intake was 2.31. During the pre-post analysis periods, no significant increase in reported safety events were identified (10 vs. 9 per 1,000 patient encounters). CONCLUSION: Implementation of a novel multifaceted process redesign including an attending physician-driven intake model had a clinically positive impact on ED flow. Validation of this model should be conducted in other practice settings. PMID- 27184244 TI - The Ask Me to Explain Campaign: A 90-Day Intervention to Promote Patient and Family Involvement in Care in a Pediatric Emergency Department. AB - BACKGROUND: Patient satisfaction is a central outcome measure of patient-centered care and is associated with improved patient safety, but the effect of specific interventions in pediatric emergency medicine on patient satisfaction is not well studied. In 2013 the University of Chicago Medicine Comer Children's Hospital's Pediatric Emergency Department identified substantial room for improvement in communication both among physicians and nurses and between hospital staff and patients. A pilot study was conducted to quantify the impact of a specific package of improvement activities on patient satisfaction in the Pediatric Emergency Department. METHODS: Using a 90-day action plan (December 2013- February 2014), the Ask Me to Explain campaign included visual signage to remind clinicians and staff to focus on addressing the concerns of their patients. Providers were educated on the campaign tools, their purpose, and how to use them to initiate discussion and provide answers to patient concerns. Education was then spread to support staff throughout the department. The primary outcome measure was the response to questions on a patient satisfaction survey delivered by a third-party vendor, specifically, "Likelihood of your recommending our Emergency Department to others." RESULTS: "Top Box" scores increased for all questions during the 90-day intervention period. Specifically, staff sensitivity to patient concerns increased from 44.0% to 59.2% (p = 0.041), and patient satisfaction with being informed about delays increased from 34.7% to 51.1% (p = 0.024). Interestingly, patient satisfaction either remained above baseline or continued to improve for all questions after the campaign had concluded. CONCLUSION: A 90-day action plan may provide a successful template for improving communication between providers and patients in a pediatric emergency department or in other health care settings. PMID- 27184245 TI - Patient-Centered Care: Just Ask a Thoughtful Question and Listen. PMID- 27184247 TI - Better Overall Survival for Breast Cancer Patients by Adding Breast Ultrasound to Follow-Up Examinations for Early Detection of Locoregional Recurrence-A Survival Impact Study. AB - We retrospectively reviewed patient records to evaluate the effectiveness of our 15 y of ultrasound (US) surveillance of recurrent breast disease in comparison with mammography (MM) and clinical examination. From 4796 stage 0-III breast cancer patients who had received surgical treatment, we identified locoregional recurrence (LRR) in 161 patients. The mean age of the 161 patients was 48 y (27 82 y), and the mean follow-up interval was 77.2 mo (11-167 mo). The methods of LRR detection, sites of LRR and overall survival (OS) were examined. Multivariate Cox survival analysis showed significantly better survival in groups detected by US (hazard ratio = 0.6, p = 0.042). The 10-y LRR OS by detection types for US (n = 69), clinical examination (n = 78) and MM (n = 8) were 58.5%, 33.1% and 100%, respectively (p = 0.0004). US was seen with better OS associated with the effective early detection of non-palpable LRR breast cancer, which is mostly not detectable on MM. PMID- 27184248 TI - A Novel Approach to Ultrasound-Mediated Tissue Decellularization and Intra Hepatic Cell Delivery in Rats. AB - Liver transplantation is the mainstay of treatment for end stage liver diseases, including metabolic and congenital liver diseases. The number of suitable donor organs is, however, limited, and a whole-liver transplant requires complex surgery. Cell therapy, such as intra-portal hepatocytes transplantation, has been considered as a bridging therapy to liver transplantation but has shown a mixed clinical outcome with limited success, including low level of engraftment of transplanted hepatocytes. Here, we report a novel cell delivery technique in a rat model by creating a cavity inside the liver parenchyma by non-invasive high intensity focused ultrasound histotripsy. Our in vivo experimental results together with histologic observations show that direct injection of cells inside the cavity can facilitate successful uptake, proliferation and integration of the transplanted hepatocytes in the recipient liver. We were able to restore the plasma albumin level to 50% of the normal level in Nagase analbuminemic rats (serum albumin level of the Nagase rats was initially nil) by cell therapy after high intensity focused ultrasound-mediated histotripsy. We believe that this novel technique would enable the delivery of a large number of cells into the liver to restore liver function, particularly as a treatment for metabolic liver diseases. This novel method of intra-hepatic hepatocyte transplantation might be an invaluable tool for cell therapy in the future. PMID- 27184249 TI - [Cushing's syndrome in a patient with macronodular adrenal hyperplasia secondary to aberrant hormone receptors]. PMID- 27184252 TI - The ball vanishes in the air: can we blame representational momentum? AB - In the vanishing ball illusion (VBI), the magician throws a ball up into the air twice and then pretends to do a third throw. On the third (fake) throw, the audience sees the ball go up and then disappear. In this article, we study the psychological mechanisms at play in this magic trick. We test the hypothesis that the illusion is based on representational momentum (RM), a psychological phenomenon in which the observer perceives the stopping point of a moving scene as being located farther ahead in the direction of motion than it really is. To determine whether the mechanisms involved in VBI are similar to those underlying RM, we compared the results of a standard VBI task to those obtained on an RM task designed to be very close to the VBI task. The results showed that VBI sensitivity was not associated with a higher anticipation score on the RM task. Unexpectedly, we found that participants who were sensitive to the illusion even obtained a weaker RM effect. We discuss several hypotheses that might account for these results. PMID- 27184251 TI - The effectiveness of email-based exercises in promoting psychological wellbeing and healthy lifestyle: a two-year follow-up study. AB - BACKGROUND: Web-based interventions provide a possibility to enhance well-being in large groups of people. Only a few studies have studied the effectiveness of the interventions and there is no information on the sustainability of the effects. Study aims were to investigate both the short (2-month) and long-term (2 year) effects of email-based training for mental health and lifestyle. METHODS: Persons who completed an 'Electronic Health Check', as advertised in a TV program, were offered a chance to participate in email-based interventions. The baseline questionnaire was completed by 73 054 people, with 42 761 starting interventions, and 16 499 people participating in at least one of the follow-ups. Persons who did not choose to start the interventions served as controls. RESULTS: At baseline, the intervention group had a higher level of stress and lower gratitude and confidence in the future than the control group. Both groups showed improvement in the level of stress, but improvement was more marked in the intervention group (P < .001 for both time points). In confidence in the future and gratitude, people who chose interpersonal interventions showed significant improvements at both time points (P < .001), whereas those choosing lifestyle interventions showed improvement only at the 2-month follow-up. Participants who had done the exercises according to instructions had the most sustained improvements in measures of psychological health at the 2-year follow-up. As for lifestyle, people who had started lifestyle interventions increased their exercise (P < .001 at both time points). CONCLUSIONS: Internet-based interventions are feasible for mental health promotion and should be available for people interested in improving their psychological well-being and lifestyle. PMID- 27184250 TI - Potential neuroimaging biomarkers of pathologic brain changes in Mild Cognitive Impairment and Alzheimer's disease: a systematic review. AB - BACKGROUND: Neuroimaging-biomarkers of Mild Cognitive Impairment (MCI) allow an early diagnosis in preclinical stages of Alzheimer's disease (AD). The goal in this paper was to review of biomarkers for Mild Cognitive Impairment (MCI) and Alzheimer's disease (AD), with emphasis on neuroimaging biomarkers. METHODS: A systematic review was conducted from existing literature that draws on markers and evidence for new measurement techniques of neuroimaging in AD, MCI and non demented subjects. Selection criteria included: 1) age >= 60 years; 2) diagnosis of AD according to NIAAA criteria, 3) diagnosis of MCI according to NIAAA criteria with a confirmed progression to AD assessed by clinical follow-up, and 4) acceptable clinical measures of cognitive impairment, disability, quality of life, and global clinical assessments. RESULTS: Seventy-two articles were included in the review. With the development of new radioligands of neuroimaging, today it is possible to measure different aspects of AD neuropathology, early diagnosis of MCI and AD become probable from preclinical stage of AD to AD dementia and non-AD dementia. CONCLUSIONS: The panel of noninvasive neuroimaging biomarkers reviewed provides a set methods to measure brain structural and functional pathophysiological changes in vivo, which are closely associated with preclinical AD, MCI and non-AD dementia. The dynamic measures of these imaging biomarkers are used to predict the disease progression in the early stages and improve the assessment of therapeutic efficacy in these diseases in future clinical trials. PMID- 27184253 TI - A prospective evaluation of chronic Babesia microti infection in seroreactive blood donors. AB - BACKGROUND: Babesia microti is the foremost infectious risk to the US blood supply for which a Food and Drug Administration (FDA)-licensed test is unavailable for donation screening. Characterization of the antibody response to B. microti and correlation with parasitemia is necessary to guide screening and donor management policies. STUDY DESIGN AND METHODS: During an FDA licensure trial, blood donors were prospectively screened (July-November 2013) using a B. microti-specific antibody enzyme immunoassay (EIA, Immunetics) in highly endemic (New York [NY]; n = 13,688), moderately endemic (Minnesota [MN]; n = 4583), and nonendemic (New Mexico [NM]; n = 8451) regions. Blood donors with repeat-reactive (RR) results participated in a 12-month prospective cohort study using B. microti EIA, immunofluorescent assay, polymerase chain reaction (PCR), blood smear, and clinical questionnaire. RESULTS: Thirty-seven (61.67%; 24 NY, seven MN, six NM) of 60 eligible RR donors enrolled in the study; 20 of 37 (54%) completed the 12 month follow-up visit of which 15 (75%) were still seroreactive. Nine PCR positive donors were identified during index screening; five participated in the follow-up study, three were PCR positive at 6 months, and two remained positive at final follow-up (378 and 404 days). Most RR donors displayed low-level seroreactivity that was either stable or waning during follow-up. The level and pattern of reactivity correlated poorly with PCR positivity. CONCLUSION: The findings indicate prolonged seropositivity in blood donors. Although rare, asymptomatic, persistent PCR positivity supports the current policy of indefinite deferral for donors with a history of babesiosis or positive test results. Repeat testing by PCR and serology will be necessary if reinstatement is to be considered. PMID- 27184255 TI - Efficient Enantioselective Biocatalytic Production of a Chiral Intermediate of Sitagliptin by a Newly Filamentous Fungus Isolate. AB - (S)-3-Hydroxy-1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin 7(8H)-yl)-4-(2,4,5-trifluorophenyl)butan-1-one ((S)-HTPP) is a crucial intermediate for the synthesis of Sitagliptin. A fungal strain ZJPH1308, capable of the biocatalysis of ketoamide 4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro [1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-one (OTPP) to (S)-HTPP with excellent enantioselectivity, was isolated from a soil sample and identified as Rhizopus microsporus var. rhizopodiformis ZJPH1308 based on its morphological characteristics and internal transcribed spacer (ITS) sequence. Some key reaction parameters involved in the bioreduction catalyzed by isolate ZJPH1308 were then optimized. It demonstrated that the bioreduction of OTPP was effective conducted at relative high temperature (45 degrees C), along with distilled water as reaction medium and glycerol-coupling approach for cofactor regeneration. Under the optimal conditions, the preparative-scale bioreduction gave a 93.2 % yield (with >99.9 % of enantiomeric excess (ee)) at 15 mM of OTPP and 45 degrees C, reaction for 24 h. The results indicated that fungal isolate ZJPH1308 can afford a thermostable carbonyl reductase and is a promising biocatalyst for clean and efficient production of valuable chiral intermediate. PMID- 27184254 TI - HE4 promotes collateral resistance to cisplatin and paclitaxel in ovarian cancer cells. AB - BACKGROUND: Chemotherapy resistance presents a difficult challenge in treating epithelial ovarian cancer patients, particularly when tumors exhibit resistance to multiple chemotherapeutic agents. A few studies have shown that elevated serum levels of the ovarian cancer biomarker HE4 correlate with tumor chemoresistance, response to treatment, and survival. Here, we sought to confirm our previous results that HE4 contributes to collateral resistance to cisplatin and paclitaxel in vitro and uncover factors that may contribute to HE4-mediated chemoresistance. METHODS: MTS assays and western blots for cleaved PARP were used to assess resistance of HE4-overexpressing SKOV3 and OVCAR8 clones to cisplatin and paclitaxel. CRISPR/Cas technology was used to knockdown HE4 in HE4-overexpressing SKOV3 cells. A microarray was conducted to determine differential gene expression between SKOV3 null vector-transfected and HE4-overexpressing clones upon cisplatin exposure, and results were validated by quantitative RT-PCR. Regulation of mitogen activated protein kinases (MAPKs) and tubulins were assessed by western blot. RESULTS: HE4-overexpressing SKOV3 and OVCAR8 clones displayed increased resistance to cisplatin and paclitaxel. Knockdown of HE4 in HE4 overexpressing SKOV3 cells partially reversed chemoresistance. Microarray analysis revealed that HE4 overexpression resulted in suppression of cisplatin mediated upregulation of EGR1, a MAPK-regulated gene involved in promoting apoptosis. Upregulation of p38, a MAPK activated in response to cisplatin, was suppressed in HE4-overexpressing clones. No differences in extracellular signal regulated kinase (ERK) activation were noted in HE4-overexpressing clones treated with 25 MUM cisplatin, but ERK activation was partially suppressed in HE4 overexpressing clones treated with 80 MUM cisplatin. Furthermore, treatment of cells with recombinant HE4 dramatically affected ERK activation in SKOV3 and OVCAR8 wild type cells. Recombinant HE4 also upregulated alpha-tubulin and beta tubulin levels in SKOV3 and OVCAR8 cells, and microtubule associated protein tau (MAPT) gene expression was increased in SKOV3 HE4-overexpressing clones. CONCLUSIONS: Overexpression of HE4 promotes collateral resistance to cisplatin and paclitaxel, and downregulation of HE4 partially reverses this chemoresistance. Multiple factors could be involved in HE4-mediated chemoresistance, including deregulation of MAPK signaling, as well as alterations in tubulin levels or stability. PMID- 27184256 TI - Immobilization of Candida antarctica Lipase B on Magnetic Poly(Urea-Urethane) Nanoparticles. AB - Poly(urea-urethane) (PUU) nanoparticles with encapsulated superparamagnetic magnetite (Fe3O4) were obtained by interfacial miniemulsion polymerization and used as support for immobilization of lipase B from Candida antarctica (CALB). CALB enzyme was immobilized on magnetic PUU nanoparticles in two steps. The enzyme was immobilized in the lyophilized nanoparticles (magnetic PUU) after the support synthesis in phosphate buffer (pH 7.6) containing CALB, by the contact between nanoparticles and enzymatic solution. The mixture was incubated at 30 degrees C in an orbital shaker during 0.5 until 6 h to determine the time for maximum immobilization efficiency. The enzyme activity was determined by esterification reactions between lauric acid and propanol. Residual activities above 95 % in relation to free enzyme were obtained in 1 h of immobilization with enzyme concentration of 0.55 mg/mL. FTIR spectrum and SEM-FEG images were used to confirm the presence of CALB on magnetic support after immobilization and stability of support even after immobilization process, respectively. Thermal (40, 60, and 80 degrees C) and pH (pH 4, 7, and 10) stabilities, storage stability, and reuse were evaluated. CALB immobilized derivatives showed high stabilities with residual activities of 95, 100, and 100 % at 40, 60, and 80 degrees C, respectively, in 6 h of incubation. After incubation in different pH values, CALB immobilized derivative presented activities of 81, 76, and 69 % in relation to activities in the beginning of the stabilization process in pH 4, 7, and 10, respectively. Furthermore, CALB immobilized derivative reduces only 15 % of its activity after 30 days of storage at 4 degrees C. Reuse results showed that immobilized CALB on magnetic PUU nanoparticles led to 95 % of geranyl oleate conversion after 8 cycles of application demonstrating high stability of the CALB immobilized derivative under different conditions. PMID- 27184258 TI - Corrigendum to "Left ventricular structural and functional abnormalities in dogs with hyperadrenocorticism" [J Vet Cardiol 17 (3) (2015) 173-181]. PMID- 27184257 TI - MicroRNA-663a is downregulated in non-small cell lung cancer and inhibits proliferation and invasion by targeting JunD. AB - BACKGROUND: MicroRNA-663a expression is downregulated in several tumors. However, its functions and mechanisms in human non-small cell lung (NSCLC) cancer remain obscure. The present study aimed to identify the expression pattern, biological roles and potential mechanisms by which miR-663a dysregulation is associated with NSCLC. METHODS: We examined expression level of miR-663a in 62 cases of NSCLC tissues and 5 NSCLC cell lines by reverse transcription PCR. In vitro, gain-of function and loss-of-function experiments were performed to examine the impact of miR-663a on proliferation, cell cycle progression and invasion of NSCLC cells. Using fluorescence reporter assays, we also explored the potential targets and possible mechanisms of miR-663a in NSCLC cells. RESULTS: Downregulation of miR 663a was observed in 42 of 62 of lung cancer tissues compared with paired normal tissues (mean cancer/normal value = 0.745) and its downregulation correlated with nodal metastasis. Transfection of miR-663a mimic suppressed cell proliferation, cell cycle progression and invasion, with downregulation of cyclin D1, cyclin E and MMP9 in both H460 and H1299 cell lines. Transfection of miR-663a inhibitor in both H460 and H1299 cell lines exhibited the opposite effects. In addition, we confirmed that miR-663a could inhibit AP-1 activity and AP-1 component JunD was a direct target of miR-663a in lung cancer cells. Transfection of miR-663a mimic downregulated JunD expression. In addition, JunD siRNA treatment abrogated miR 663a inhibitor-induced expression of cyclin D1, cyclin E and MMP9. Above all, both miRNA mimic and inhibitor in two different NSCLC cell lines demonstrated that miR-663a inhibits proliferation and invasion by targeting AP-1 transcription factor JunD. CONCLUSIONS: This study indicates that miR-663a downregulation might be associated with NSCLC progression. MiR-663a suppresses proliferation and invasion by targeting AP-1 component JunD in NSCLC cells. PMID- 27184260 TI - Enhancing Specific Energy and Power in Asymmetric Supercapacitors - A Synergetic Strategy based on the Use of Redox Additive Electrolytes. AB - The strategy of using redox additive electrolyte in combination with multiwall carbon nanotubes/metal oxide composites leads to a substantial improvements in the specific energy and power of asymmetric supercapacitors (ASCs). When the pure electrolyte is optimally modified with a redox additive viz., KI, ~105% increase in the specific energy is obtained with good cyclic stability over 3,000 charge discharge cycles and ~14.7% capacitance fade. This increase is a direct consequence of the iodine/iodide redox pairs that strongly modifies the faradaic and non-faradaic type reactions occurring on the surface of the electrodes. Contrary to what is shown in few earlier reports, it is established that indiscriminate increase in the concentration of redox additives will leads to performance loss. Suitable explanations are given based on theoretical laws. The specific energy or power values being reported in the fabricated ASCs are comparable or higher than those reported in ASCs based on toxic acetonitrile or expensive ionic liquids. The paper shows that the use of redox additive is economically favorable strategy for obtaining cost effective and environmentally friendly ASCs. PMID- 27184261 TI - Does Exercise Reduce Aggressive Feelings? An Experiment Examining the Influence of Movement Type and Social Task Conditions on Testiness and Anger Reduction. AB - In the present study, it was assumed that a decrease in aggressive feelings is stronger with movements that are unlike aggressive actions compared with those that are similar to aggressive actions. Furthermore, cooperative exercise tasks were expected to lead to lower aggressive feelings compared with competitive tasks. After undergoing an induction of aggressive feelings, 60 participants were randomly assigned to one of six experimental treatment groups, each differing in "movement type" (rowing and combat exercise) and "social task condition" (cooperation, competition, and individualization). A significant reduction of aggressive feelings was only found for participants exercising individually in the rowing condition compared with the individual combat exercise condition. There were no sole effects of "movement type" and "social task condition." PMID- 27184259 TI - Discovery, Development, and Adoption of Medications to Treat Alcohol Use Disorder: Goals for the Phases of Medications Development. AB - For more than 25 years, advances have been made in developing medications to treat alcohol use disorder (AUD), highlighted by the U.S. Food and Drug Administration's approval of naltrexone (oral and long-acting) and acamprosate. Despite this progress, more work remains to be done in this area because these medications, although effective for some people, do not work for everyone. A high priority for the National Institute on Alcohol Abuse and Alcohol is to put into place a solid infrastructure to aid in the development of medications that are more effective than those currently available and with few side effects. Medication development, especially for a disorder as complex as AUD, is challenging and involves multiple phases, including discovery of "druggable" targets, preclinical studies, human clinical trials, and the adoption and implementation of the new medication into mainstream medicine. A successful medications development program requires clearly established goals for each phase to ensure that a candidate compound is not trapped in one particular phase, a condition known as "the valley of death." In this article, the phases of medication development are described as they apply to AUD, and specific goals of each phase are identified for the next decade. In addition, several important crosscutting themes are outlined for each phase, all of which are essential for advancing medications development. These include identifying and validating screening models and druggable targets, making use of precision medicine, and establishing partnerships among key stakeholders. Our goal in writing this article is to provide a guide on medications development that will aid the alcohol research community in planning, testing, and developing medications for AUD. PMID- 27184262 TI - US physicians can and should ask patients about firearms, experts argue. PMID- 27184263 TI - Synthesis and Antifungal Activity of Some 4,6-Dimethylisoxazolo[3,4- b]pyridin 3(1H)-one Derivatives. AB - BACKGROUND: Cutaneous and invasive fungal infections are constant threats to human health that substantiate the need for the development of new efficacious and safe antimycotics. METHODS: A series of N1-alkyl, N1-acyl and N1-sulfonyl derivatives of 4,6- dimethylisoxazolo[3,4-b]pyridin-3(1H)-one (1) were synthesized. The antimicrobial activities of title compounds against 21 pathogenic yeast-like fungal clinical isolates and 5 reference strains were evaluated by means of a broth microdilution method. RESULTS: Among the compounds tested, the newly prepared N1-benzoyl (2m) and N1-(4-fluorobenzoyl) (2n) derivatives of 1 showed 81% and 95% inhibitory efficacy, respectively, against the clinical isolates, which were comparable to that of the reference drug fluconazole. The strains that exhibited the highest susceptibility to the compound 2n included Candida utilis (MIC < 6.2 MUg/mL), C. parapsilosis (MIC in the range <6.2 - 12.5 MUg/mL), Geotrichum candidum (MIC = 12.5 MUg/mL) as well as C. lusitaniae and Rhodotorula mucilaginosa (MIC = 25 MUg/mL). CONCLUSION: In terms of MIC, compound 2n proved to be four times more active against the clinical isolates of Candida albicans and C. albicans ATCC 10231 standard strain than fluconazole, the widely prescribed antifungal agent for mucosal and systemic yeast infections (MIC = 50 vs 200 MUg/mL). PMID- 27184264 TI - cDNA Microarray Analysis Revealing Candidate Biomineralization Genes of the Pearl Oyster, Pinctada fucata martensii. AB - Biomineralization is a common biological phenomenon resulting in strong tissue, such as bone, tooth, and shell. Pinctada fucata martensii is an ideal animal for the study of biomineralization. Here, microarray technique was used to identify biomineralization gene in mantle edge (ME), mantle center (MC), and both ME and MC (ME-MC) for this pearl oyster. Results revealed that 804, 306, and 1127 contigs expressed at least three times higher in ME, MC, and ME-MC as those in other tissues. Blast against non-redundant database showed that 130 contigs (16.17 %), 53 contigs (17.32 %), and 248 contigs (22.01 %) hit reference genes (E <= -10), among which 91 contigs, 48 contigs, and 168 contigs could be assigned to 32, 26, and 63 biomineralization genes in tissue of ME, MC, and ME-MC at a threshold of 3 times upregulated expression level. The ratios of biomineralization contigs to homologous contigs were similar at 3 times, 10 times, and 100 times of upregulated expression level in either ME, MC, or ME-MC. Moreover, the ratio of biomineralization contigs was highest in MC. Although mRNA distribution characters were similar to those in other studies for eight biomineralization genes of PFMG3, Pif, nacrein, MSI7, mantle gene 6, Pfty1, prismin, and the shematrin, most biomineralization genes presented different expression profiles from existing reports. These results provided massive fundamental information for further study of biomineralization gene function, and it may be helpful for revealing gene nets of biomineralization and the molecular mechanisms underlining formation of shell and pearl for the oyster. PMID- 27184267 TI - Development of an ultra high performance liquid chromatography method for determining triamcinolone acetonide in hydrogels using the design of experiments/design space strategy in combination with process capability index. AB - An ultra high performance liquid chromatography method was developed and validated for the quantitation of triamcinolone acetonide in an injectable ophthalmic hydrogel to determine the contribution of analytical method error in the content uniformity measurement. During the development phase, the design of experiments/design space strategy was used. For this, the free R-program was used as a commercial software alternative, a fast efficient tool for data analysis. The process capability index was used to find the permitted level of variation for each factor and to define the design space. All these aspects were analyzed and discussed under different experimental conditions by the Monte Carlo simulation method. Second, a pre-study validation procedure was performed in accordance with the International Conference on Harmonization guidelines. The validated method was applied for the determination of uniformity of dosage units and the reasons for variability (inhomogeneity and the analytical method error) were analyzed based on the overall uncertainty. PMID- 27184266 TI - Preoperative predictors for outcomes after total hip replacement in patients with osteoarthritis: a systematic review. AB - BACKGROUND: This systematic review examines which patient related factors influence functional and clinical outcomes after total hip arthroplasty (THA) in patients with hip osteoarthritis (OA). METHODS: We performed a systematic review according to the PRISMA guidelines. We searched databases and trial registries for prospective studies including OA patients who underwent primary THA. Studies with preoperative measurements on predictors, with at least 1 year follow-up were included. Risk of bias and confounding was assessed for two domains: follow-up rate and looking at independent effects. RESULTS: Thirty-five studies were included (138,039 patients). Only nine studies (29 %) had low risk of bias for all domains thus suggesting an overall low quality of evidence. Studies were heterogeneous in the predictors tested and in the observed directions of the associations. Overall, preoperative function (13 studies (37 %), 2 with low risk of bias) and radiological OA (6 studies (17 %), 1 with low risk of bias) were predictors with the most consistent findings. Worse preoperative function and more severe radiological OA were associated with larger postoperative improvement. However, these patients never reached the level of postoperative functioning as patients with better preoperative function or less severe radiological OA. For age, gender, comorbidity, pain and quality of life the results of studies were conflicting. For BMI, some studies (n = 5, 2 with low risk of bias) found worse outcomes for patients with higher BMI. However, substantial improvement was still achieved regardless of their BMI. CONCLUSION: There is not enough evidence to draw succinct conclusions on preoperative predictors for postoperative outcome in THA, as results of studies are conflicting and the methodological quality is low. Results suggest to focus on preoperative function and radiological osteoarthritis to decide when THA will be most effective. The present mapping of current evidence on the relationship between patient related factors and outcomes provides better information compared to individual studies and may help to set patient expectations before surgery. In addition, these findings may contribute to discussions on how to achieve the best possible postoperative outcome for specific patient groups. TRIAL REGISTRATION: This systematic review was registered in Prospero, registration number RD42014009977 . PMID- 27184265 TI - Ethical considerations of e-cigarette use for tobacco harm reduction. AB - Due to their similarity to tobacco cigarettes, electronic cigarettes (e cigarettes) could play an important role in tobacco harm reduction. However, the public health community remains divided concerning the appropriateness of endorsing a device whose safety and efficacy for smoking cessation remain unclear. We identified the major ethical considerations surrounding the use of e cigarettes for tobacco harm reduction, including product safety, efficacy for smoking cessation and reduction, use among non-smokers, use among youth, marketing and advertisement, use in public places, renormalization of a smoking culture, and market ownership. Overall, the safety profile of e-cigarettes is unlikely to warrant serious public health concerns, particularly given the known adverse health effects associated with tobacco cigarettes. As a result, it is unlikely that the population-level harms resulting from e-cigarette uptake among non-smokers would overshadow the public health gains obtained from tobacco harm reduction among current smokers. While the existence of a gateway effect for youth remains uncertain, e-cigarette use in this population should be discouraged. Similarly, marketing and advertisement should remain aligned with the degree of known product risk and should be targeted to current smokers. Overall, the available evidence supports the cautionary implementation of harm reduction interventions aimed at promoting e-cigarettes as attractive and competitive alternatives to cigarette smoking, while taking measures to protect vulnerable groups and individuals. PMID- 27184268 TI - Skin barrier modification with organic solvents. AB - The primary barrier to body water loss and influx of exogenous substances resides in the stratum corneum (SC). The barrier function of the SC is provided by patterned lipid lamellae localized to the extracellular spaces between corneocytes. SC lipids are intimately involved in maintaining the barrier function. It is generally accepted that solvents induce cutaneous barrier disruption. The main aim of this work is the evaluation of the different capability of two solvent systems on inducing changes in the SC barrier function. SC lipid modifications will be evaluated by lipid analysis, water sorption/desorption experiments, confocal-Raman visualization and FSTEM images. The amount of SC lipids extracted by chloroform/methanol was significantly higher than those extracted by acetone. DSC results indicate that acetone extract has lower temperature phase transitions than chloroform/methanol extract. The evaluation of the kinetics of the moisture uptake and loss demonstrated that when SC is treated with chloroform/methanol the resultant sample reach equilibrium in shorter times indicating a deterioration of the SC tissue with higher permeability. Instead, acetone treatment led to a SC sample with a decreased permeability thus with an improved SC barrier function. Confocal-Raman and FSTEM images demonstrated the absence of the lipids on SC previously treated with chloroform/methanol. However, they were still present when the SC was treated with acetone. Results obtained with all the different techniques used were consistent. The results obtained increases the knowledge of the interaction lipid solvent, being this useful for understanding the mechanism of reparation of damaged skin. PMID- 27184271 TI - The 2015 Dietary Guidelines Advisory Committee Scientific Report: Development and Major Conclusions. AB - The Dietary Guidelines for Americans (DGA) is published every 5 y jointly by the Department of Health and Human Services (HHS) and the USDA and provides a framework for US-based food and nutrition programs, health promotion and disease prevention initiatives, and research priorities. Summarized in this report are the methods, major conclusions, and recommendations of the Scientific Report of the 2015 US Dietary Guidelines Advisory Committee (DGAC). Early in the process, the DGAC developed a conceptual model and formulated questions to examine nutritional risk and determinants and impact of dietary patterns in relation to numerous health outcomes among individuals aged >=2 y. As detailed in the report, an expansive, transparent, and comprehensive process was used to address each question, with multiple opportunities for public input included. Consensus was reached on all DGAC's findings, including each conclusion and recommendation, and the entire report. When research questions were answered by original systematic literature reviews and/or with existing, high-quality expert reports, the quality and strength of the evidence was formally graded. The report was organized around the following 5 themes: 1) food and nutrient intakes and health: current status and trends; 2) dietary patterns, foods and nutrients, and health outcomes; 3) diet and physical activity behavior change; 4) food and physical activity environments; and 5) food sustainability and food safety. The following 3 cross cutting topics were addressed: 1) sodium, 2) saturated fat, and 3) added sugars. Physical activity recommendations from recent expert reports were endorsed. The overall quality of the American diet was assessed to identify overconsumed and underconsumed nutrients of public health concern. Common food characteristics of healthy dietary patterns were determined. Features of effective interventions to change individual and population diet and physical activity behaviors in clinical, public health, and community settings were identified. The report was used by the HHS and the USDA to develop the 2015 DGA. PMID- 27184270 TI - Perspective: A Critical Look at the Ancillary Age-Related Eye Disease Study 2: Nutrition and Cognitive Function Results in Older Individuals with Age-Related Macular Degeneration. AB - A large body of literature suggests that the dietary carotenoids lutein and zeaxanthin and long-chain polyunsaturated fatty acids such as docosahexaenoic acid are related to improved cognitive function across the life span. A recent report by the Age-Related Eye Disease Study (AREDS) group appears to contradict the general findings of others in the field. In this review, we look critically at the methods, study designs, and analysis techniques used in the larger body of literature and compare them with the recent AREDS reports. PMID- 27184269 TI - Perspective: Randomized Controlled Trials Are Not a Panacea for Diet-Related Research. AB - Research into the role of diet in health faces a number of methodologic challenges in the choice of study design, measurement methods, and analytic options. Heavier reliance on randomized controlled trial (RCT) designs is suggested as a way to solve these challenges. We present and discuss 7 inherent and practical considerations with special relevance to RCTs designed to study diet: 1) the need for narrow focus; 2) the choice of subjects and exposures; 3) blinding of the intervention; 4) perceived asymmetry of treatment in relation to need; 5) temporal relations between dietary exposures and putative outcomes; 6) strict adherence to the intervention protocol, despite potential clinical counter indications; and 7) the need to maintain methodologic rigor, including measuring diet carefully and frequently. Alternatives, including observational studies and adaptive intervention designs, are presented and discussed. Given high noise-to signal ratios interjected by using inaccurate assessment methods in studies with weak or inappropriate study designs (including RCTs), it is conceivable and indeed likely that effects of diet are underestimated. No matter which designs are used, studies will require continued improvement in the assessment of dietary intake. As technology continues to improve, there is potential for enhanced accuracy and reduced user burden of dietary assessments that are applicable to a wide variety of study designs, including RCTs. PMID- 27184272 TI - Foods, Nutrients, and Dietary Patterns: Interconnections and Implications for Dietary Guidelines. AB - Dietary guidelines provide evidence-based statements on food choices to meet nutritional requirements and reduce the risk of prevailing chronic disease. They involve a substantial amount of research translation, and their implementation has important health consequences. Foods, however, are complex combinations of nutrients and other compounds that act synergistically within the food and across food combinations. In addition, the evidence base underpinning dietary guidelines accesses research that reflects different study designs, with inherent strengths and limitations. We propose a systematic approach for the review of evidence that begins with research on dietary patterns. This research will identify the combinations of foods that best protect, or appear deleterious to, health. Next, we suggest that evidence be sought from research that focuses on the effects of individual foods. Finally, nutrient-based research should be considered to explain the mechanisms by which these foods and dietary patterns exert their effects, take into account the effects of ingredients added to the food supply, and enable assessments of dietary sufficiency. The consideration of individual nutrients and food components (e.g., upper limits for saturated fat, added sugar, and sodium) provides important benchmarks for evaluating overall diet quality. The concepts of core and discretionary foods (nutrient-rich and nutrient-poor foods, respectively) enable distinctions between foods, and this has implications for the relation between food policy and food manufacturing. In summary, evidence supporting healthy dietary patterns provides the foundation for the development of dietary guidelines. Further reference to individual foods and nutrients follows from the foundation of healthy dietary patterns. PMID- 27184273 TI - Energy Contribution and Nutrient Composition of Breakfast and Their Relations to Overweight in Free-living Individuals: A Systematic Review. AB - Previous systematic reviews on the relation between overweight or obesity and breakfast focused on the frequency of consumption and only partially accounted for breakfast nutritional profiles. Given the central role of these factors, we conducted a systematic review of the literature on this putative relation, with a specific focus on breakfast energy intake and/or breakfast composition. Among the 814 articles identified from the literature search in PubMed, 19, mostly cross sectional, studies met the inclusion criteria (i.e., studies providing a quantitative estimate of the relation between any measure of weight, overweight, and obesity and breakfast energy intake or breakfast macronutrient composition). We excluded studies in subjects with acquired metabolic disorders, such as diabetes or impaired glucose tolerance. Of the 16 studies that evaluated the amount of energy intake at breakfast, 4 found that a lower energy intake at breakfast was significantly associated with obesity in children, adolescents, and adults, whereas 2 partially overlapping studies found that a higher energy intake was significantly associated with a higher body mass index in children. Of the 8 studies investigating breakfast composition, 3 suggested that a breakfast characterized by a higher amount of carbohydrates and a lower amount of fat is significantly related to normal weight in adults, whereas the others reported mixed results. In conclusion, there is some evidence that a lower energy intake at breakfast is related to obesity, although the studies are few and heterogeneous. Studies on the nutrient composition of breakfast have shown inconsistent results. PMID- 27184274 TI - What Is a Snack, Why Do We Snack, and How Can We Choose Better Snacks? A Review of the Definitions of Snacking, Motivations to Snack, Contributions to Dietary Intake, and Recommendations for Improvement. AB - Around the world, adults consume energy outside of traditional meals such as breakfast, lunch, and dinner. However, because there is no consistent definition of a "snack," it is unclear whether those extra eating occasions represent additional meals or snacks. The manner in which an eating occasion is labeled (e.g., as a meal or a snack) may influence other food choices an individual makes on the same day and satiety after consumption. Therefore, a clear distinction between "meals" and "snacks" is important. This review aims to assess the definition of extra eating occasions, to understand why eating is initiated at these occasions, and to determine what food choices are common at these eating occasions in order to identify areas for dietary intervention and improvement. Part I of this review discusses how snacking is defined and the social, environmental, and individual influences on the desire to snack and choice of snack. The section concludes with a brief discussion of the associations of snacking with cardiometabolic health markers, especially lipid profiles and weight. Part II addresses popular snack choices, overall snacking frequencies, and the demographic characteristics of frequent snackers in several different countries. This review concludes with a recommendation for nutrition policymakers to encourage specific health-promoting snacks that address nutrient insufficiencies and excesses. PMID- 27184275 TI - Is Obesity Associated with Altered Energy Expenditure? AB - Historically, obese individuals were believed to have lower energy expenditure (EE) rates than nonobese individuals (normal and overweight), which, in the long term, would contribute to a positive energy balance and subsequent weight gain. The aim of this review was to critically appraise studies that compared measures of EE and its components, resting EE (REE), activity EE (AEE), and diet-induced thermogenesis (DIT), in obese and nonobese adults to elucidate whether obesity is associated with altered EE. Contrary to popular belief, research has shown that obese individuals have higher absolute REE and total EE. When body composition (namely the metabolically active component, fat-free mass) is taken into account, these differences between obese and nonobese individuals disappear, suggesting that EE in obese individuals is not altered. However, an important question is whether AEE is lower in obese individuals because of a decrease in overall physical activity or because of less energy expended while performing physical activity. AEE and DIT could be reduced in obese individuals, mostly because of unhealthy behavior (low physical activity, higher intake of fat). However, the current evidence does not support the hypothesis that obesity is sustained by lower daily EE or REE. Future studies, comparing EE between obese and nonobese and assessing potential physiologic abnormalities in obese individuals, should be able to better answer the question of whether these individuals have altered energy metabolism. PMID- 27184276 TI - Effect of Flavonoids on Upper Respiratory Tract Infections and Immune Function: A Systematic Review and Meta-Analysis. AB - Previous research on animals indicates flavonoid compounds have immunomodulatory properties; however, human research remains inconclusive. The aim of this systematic review was to assess the efficacy of dietary flavonoids on upper respiratory tract infections (URTIs) and immune function in healthy adults. A created search strategy was run against Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and EMBASE classic, CINAHL, and AMED. The returned studies were initially screened, and 2 reviewers independently assessed the remaining studies for eligibility against prespecified criteria. Fourteen studies, of 387 initially identified, were included in this review, and the primary outcome measure was the effect of flavonoids on URTI incidence, duration, and severity. Of the included studies, flavonoid supplementation ranged from 0.2 to 1.2 g/d. Overall, flavonoid supplementation decreased URTI incidence by 33% (95% CI: 31%, 36%) compared with control, with no apparent adverse effects. Sick day count was decreased by 40% with flavonoid supplementation, although unclear. Differences in bio-immune markers (e.g., interleukin-6, tumor necrosis factor alpha, interferon-gamma, neutrophils) were trivial between the intervention and control groups during the intervention and after exercise when a postintervention exercise bout was included. These findings suggest that flavonoids are a viable supplement to decrease URTI incidence in an otherwise healthy population. PMID- 27184277 TI - Cranberries and Urinary Tract Infections: How Can the Same Evidence Lead to Conflicting Advice? AB - Cranberry has been used traditionally to prevent urinary tract infections (UTIs), primarily among generally healthy women prone to recurrent UTIs. Results from a number of published clinical studies have supported this benefit; however, meta analyses on cranberry and UTI prevention have reported conflicting conclusions. This article explores the methodological differences that contributed to these disparate findings. Despite similar research questions, the meta-analyses varied in the studies that were included, as well as the data that were extracted. In the 2 most comprehensive systematic reviews, heterogeneity was handled differently, leading to an I(2) of 65% in one and 43% in the other. Most notably, the populations influencing the conclusions varied. In one analysis, populations with pathological/physiological conditions contributed 75.6% of the total weight to the summary risk estimate (RR: 0.86; 95% CI: 0.71, 1.04); another weighted the evidence relatively equally across UTI populations (RR: 0.62; 95% CI: 0.49, 0.80); and a third included only women with recurrent UTIs (RR: 0.53; 95% CI: 0.33, 0.83). Because women with recurrent UTIs are the group to whom most recommendations regarding cranberry consumption is directed, inclusion of other groups in the efficacy assessment could influence clinical practice quality. Therefore, conclusions on cranberry and UTIs should consider differences in results across various populations studied when interpreting results from meta analyses. PMID- 27184278 TI - Risk Factors for Malnutrition in Older Adults: A Systematic Review of the Literature Based on Longitudinal Data. AB - The present systematic review critically examines the available scientific literature on risk factors for malnutrition in the older population (aged >=65 y). A systematic search was conducted in MEDLINE, reviewing reference lists from 2000 until March 2015. The 2499 papers identified were subjected to inclusion criteria that evaluated the study quality according to items from validated guidelines. Only papers that provided information on a variable's effect on the development of malnutrition, which requires longitudinal data, were included. A total of 6 longitudinal studies met the inclusion criteria and were included in the systematic review. These studies reported the following significant risk factors for malnutrition: age (OR: 1.038; P = 0.045), frailty in institutionalized persons (beta: 0.22; P = 0.036), excessive polypharmacy (beta: 0.62; P = 0.001), general health decline including physical function (OR: 1.793; P = 0.008), Parkinson disease (OR: 2.450; P = 0.047), constipation (OR: 2.490; P = 0.015), poor (OR: 3.30; P value not given) or moderate (beta: -0.27; P = 0.016) self-reported health status, cognitive decline (OR: 1.844; P = 0.001), dementia (OR: 2.139; P = 0.001), eating dependencies (OR: 2.257; P = 0.001), loss of interest in life (beta: -0.58; P = 0.017), poor appetite (beta: -1.52; P = 0.000), basal oral dysphagia (OR: 2.72; P = 0.010), signs of impaired efficacy of swallowing (OR: 2.73; P = 0.015), and institutionalization (beta: -1.89; P < 0.001). These risk factors for malnutrition in older adults may be considered by health care professionals when developing new integrated assessment instruments to identify older adults' risk of malnutrition and to support the development of preventive and treatment strategies. PMID- 27184279 TI - The Pediatric Methionine Requirement Should Incorporate Remethylation Potential and Transmethylation Demands. AB - The metabolic demand for methionine is great in neonates. Indeed, methionine is the only indispensable sulfur amino acid and is required not only for protein synthesis and growth but is also partitioned to a greater extent to transsulfuration for cysteine and taurine synthesis and to >50 transmethylation reactions that serve to methylate DNA and synthesize metabolites, including creatine and phosphatidylcholine. Therefore, the pediatric methionine requirement must accommodate the demands of rapid protein turnover as well as vast nonprotein demands. Because cysteine spares the methionine requirement, it is likely that the dietary provision of transmethylation products can also feasibly spare methionine. However, understanding the requirement of methionine is further complicated because demethylated methionine can be remethylated by the dietary methyl donors folate and betaine (derived from choline). Intakes of dietary methyl donors are highly variable, which is of particular concern for newborns. It has been demonstrated that many populations have enhanced requirements for these nutrients, and nutrient fortification may exacerbate this phenomenon by selecting phenotypes that increase methyl requirements. Moreover, higher transmethylation rates can limit methyl supply and affect other transmethylation reactions as well as protein synthesis. Therefore, careful investigations are needed to determine how remethylation and transmethylation contribute to the methionine requirement. The purpose of this review is to support our hypothesis that dietary methyl donors and consumers can drive methionine availability for protein synthesis and transmethylation reactions. We argue that nutritional strategies in neonates need to ensure that methionine is available to meet requirements for growth as well as for transmethylation products. PMID- 27184280 TI - Is There a Role for the Enteral Administration of Serum-Derived Immunoglobulins in Human Gastrointestinal Disease and Pediatric Critical Care Nutrition? AB - Twenty years ago, there was profound, international interest in developing oral human, bovine, or chicken egg-derived immunoglobulin (Ig) for the prevention and nutritional treatment of childhood malnutrition and gastrointestinal disease, including acute diarrhea and necrotizing enterocolitis. Although such Ig products were shown to be effective, with both nutritional and antidiarrheal benefits, interest waned because of their cost and because of the perceived risk of bovine serum encephalitis (BSE). BSE is no longer considered a barrier to use of oral Ig, because the WHO has declared the United States to be BSE-free since the early 2000s. Low-cost bovine-derived products with high Ig content have been developed and are regulated as medical foods. These new products, called serum bovine Igs (SBIs), facilitate the management of chronic or severe gastrointestinal disturbances in both children and adults and are regulated by the US Food and Drug Administration. Well-established applications for use of SBIs include human immunodeficiency virus (HIV)-associated enteropathy and diarrhea-predominant irritable bowel syndrome. However, SBIs and other similar products could potentially become important components of the treatment regimen for other conditions, such as inflammatory bowel disease, by aiding in disease control without immunosuppressive side effects. In addition, SBIs may be helpful in conditions associated with the depletion of circulating and luminal Igs and could potentially play an important role in critical care nutrition. The rationale for their use is to facilitate intraluminal microbial antibody coating, an essential process in immune recognition in the gut which is disturbed in these conditions, thereby leading to intestinal inflammation. Thus, oral Ig may emerge as an important "add-on" therapy for a variety of gastrointestinal and nutritional problems during the next decade. PMID- 27184282 TI - Niacin. PMID- 27184283 TI - Plant and Animal Protein Intakes Are Differentially Associated with Large Clusters of Nutrient Intake that May Explain Part of Their Complex Relation with CVD Risk. PMID- 27184281 TI - Nutrition in Cardioskeletal Health. AB - Bone and heart health are linked through a variety of cellular, endocrine, and metabolic mechanisms, including the bidirectional effects of mineral-regulating hormones parathyroid hormone and fibroblast growth factor 23. Nutrition plays an important role in the development of both cardiovascular and bone disease. This review describes current knowledge on the relations between the cardiovascular system and bone and the influence of key nutrients involved in mineral metabolism calcium, vitamin D, and phosphorus-on heart and bone health, as well as the racial/ethnic differences in cardiovascular disease and osteoporosis and the influence that nutrition has on these disparities. PMID- 27184285 TI - Evaluating the Intervention-Based Evidence Surrounding the Causal Role of Breakfast on Markers of Weight Management, with Specific Focus on Breakfast Composition and Size. AB - Nutritional strategies are vitally needed to aid in the management of obesity. Cross-sectional and epidemiologic studies consistently demonstrate that breakfast consumption is strongly associated with a healthy body weight. However, the intervention-based long-term evidence supporting a causal role of breakfast consumption is quite limited and appears to be influenced by several key dietary factors, such as dietary protein, fiber, and energy content. This article provides a comprehensive review of the intervention-based literature that examines the effects of breakfast consumption on markers of weight management and daily food intake. In addition, specific focus on the composition and size (i.e., energy content) of the breakfast meal is included. Overall, there is limited evidence supporting (or refuting) the daily consumption of breakfast for body weight management and daily food intake. In terms of whether the type of breakfast influences these outcomes, there is accumulating evidence supporting the consumption of increased dietary protein and fiber content at breakfast, as well as the consumption of more energy during the morning hours. However, the majority of the studies that manipulated breakfast composition and content did not control for habitual breakfast behaviors, nor did these studies include a breakfast-skipping control arm. Thus, it is unclear whether the addition of these types of breakfast plays a causal role in weight management. Future research, including large randomized controlled trials of longer-term (i.e., >=6 mo) duration with a focus on key dietary factors, is critical to begin to assess whether breakfast recommendations are appropriate for the prevention and/or treatment of obesity. PMID- 27184286 TI - The Effects of Breakfast and Breakfast Composition on Cognition in Adults. AB - Extensive literature has addressed the acute cognitive effects of breaking a fast. Recent reviews in this line of work have synthesized available research on the cognitive consequences of fasting compared with nutrient intake and the cognitive effects of macronutrient consumption. These largely have been inconclusive, possibly in part because of selection criteria limiting the scope of studies covered. The purpose of the current review is to integrate the results of the literature examining the cognitive effects of breakfast and breakfast composition in adults with the use of a flexible definition of breakfast, specifically, any caloric intake after a fasting period of >=8 h. This review includes 38 studies that examine the acute cognitive impact of breakfast and 16 studies that examine the effects of breakfast composition. Results suggest that healthy adults show a small but robust advantage for memory (particularly delayed recall) from consuming breakfast. Largely equivocal results emerge for attention and motor and executive function; there were no effects from breakfast on language. Regarding breakfast composition, a smaller number of studies and widely disparate methodology addressing this question preclude definitive conclusions about the effects of cognition. A subset of this literature examines these questions in the context of glucoregulation; the findings emphasize the importance of considering differences in glucoregulation in research designs, even among healthy cohorts. The limitations of this literature include methodologic differences, such as the use of different tests to measure cognitive constructs, as well as the effects of timing in test administration. PMID- 27184287 TI - The Effects of Breakfast and Breakfast Composition on Cognition in Children and Adolescents: A Systematic Review. AB - Breakfast is thought to be beneficial for cognitive and academic performance in school children. However, breakfast is the most frequently skipped meal, especially among adolescents. The aim of the current article was to systematically review the evidence from intervention studies for the effects of breakfast on cognitive performance in children and adolescents. The effects of breakfast were evaluated by cognitive domain and breakfast manipulation. A total of 45 studies reported in 43 articles were included in the review. Most studies considered the acute effect of a single breakfast (n = 34). The acute studies looked at breakfast compared with no breakfast (n = 24) and/or comparisons of breakfast type (n = 15). The effects of chronic school breakfast program interventions were evaluated in 11 studies. The findings suggest that breakfast consumption relative to fasting has a short-term (same morning) positive domain specific effect on cognition. Tasks requiring attention, executive function, and memory were facilitated more reliably by breakfast consumption relative to fasting, with effects more apparent in undernourished children. Firm conclusions cannot be made about the acute effects of breakfast composition and the effects of chronic breakfast interventions because there are too few studies and these largely report inconsistent findings. This review also highlights methodologic limitations of the existing research. These include a lack of research on adolescents, few naturalistic breakfast manipulations or testing environments, small samples, and insensitive cognitive tests. PMID- 27184289 TI - Atypical temperature-dependence of symmetry transformation observed in a uranyl phosphonate. AB - The example of phase transformation from a centrosymmetric space group at low temperature (LT) to a chiral space group at high temperature (HT) is reported, which was clearly resolved in a single-crystal-to-single-crystal manner in a 3D uranyl(vi) phosphonate compound [TMA][(UO2)2(1,3-pbpH)(1,3-pbpH2)] () (TMA(+) = tetramethylammonium cation; 1,3-pbpH4 = 1,3-phenylenebis(phosphonic acid)). PMID- 27184288 TI - The Effects of Breakfast Consumption and Composition on Metabolic Wellness with a Focus on Carbohydrate Metabolism. AB - Findings from epidemiologic studies indicate that there are associations between breakfast consumption and a lower risk of type 2 diabetes mellitus (T2DM) and metabolic syndrome, prompting interest in the influence of breakfast on carbohydrate metabolism and indicators of T2DM risk. The objective of this review was to summarize the available evidence from randomized controlled trials assessing the impact of breakfast on variables related to carbohydrate metabolism and metabolic wellness. Consuming compared with skipping breakfast appeared to improve glucose and insulin responses throughout the day. Breakfast composition may also be important. Dietary patterns high in rapidly available carbohydrate were associated with elevated T2DM risk. Therefore, partial replacement of rapidly available carbohydrate with other dietary components, such as whole grains and cereal fibers, proteins, and unsaturated fatty acids (UFAs), at breakfast may be a useful strategy for producing favorable metabolic outcomes. Consumption of fermentable and viscous dietary fibers at breakfast lowers glycemia and insulinemia. Fermentable fibers likely act through enhancing insulin sensitivity later in the day, and viscous fibers have an acute effect to slow the rate of carbohydrate absorption. Partially substituting protein for rapidly available carbohydrate enhances satiety and diet-induced thermogenesis, and also favorably affects lipoprotein lipids and blood pressure. Partially substituting UFA for carbohydrate has been associated with improved insulin sensitivity, lipoprotein lipids, and blood pressure. Overall, the available evidence suggests that consuming breakfast foods high in whole grains and cereal fiber, while limiting rapidly available carbohydrate, is a promising strategy for metabolic health promotion. PMID- 27184290 TI - Rescue baroreflex activation therapy after Stanford B aortic dissection due to therapy-refractory hypertension. AB - Clinical trials have demonstrated significant and durable reduction in arterial pressure from baroreflex activation therapy (BAT) in patients with resistant arterial hypertension. There is a lack of data, however, concerning the use of BAT in a rescue approach during therapy-refractory hypertensive crisis resulting in life-threatening end-organ damage. Here, we describe the first case in which BAT was applied as a rescue procedure in an intensive care setting after ineffective maximum medical treatment. A 34-year-old male patient presented with Stanford B aortic dissection and hypertensive crisis. The dissection membrane extended from the left subclavian artery down to the right common iliac artery, resulting in a total arterial occlusion of the right leg. After emergency thoracic endovascular aortic repair and femorofemoral crossover bypass, the patient developed a compartment syndrome of the right lower limb, ultimately leading to amputation of the right leg above the knee. Even under deep sedation recurrent hypertensive crises of up to 220 mm Hg occurred that could not be controlled by eight antihypertensive drugs of different classes. Screening for secondary hypertension was negative. Eventually, rescue implantation of right sided BAT was performed as a bailout procedure, followed by immediate activation of the device. After a hospital stay of a total of 8 weeks, the patient was discharged 2 weeks after BAT initiation with satisfactory blood pressure levels. After 1-year follow-up, the patient has not had a hypertensive crisis since the onset of BAT and is currently on fourfold oral antihypertensive therapy. The previously described bailout procedures for the treatment of life-threatening hypertensive conditions that are refractory to drug treatment have mainly comprised the interventional denervation of renal arteries. The utilization of BAT is new in this emergency context and showed a significant, immediate, and sustained reduction of blood pressure levels after activation. To our knowledge, we report the first case of an immediate activation of a barostim while the device is usually not activated before 2 to 4 weeks after implantation to allow time for the surgical site to heal. During the follow-up period, the healing process was not impaired, and a significant, immediate, and sustained reduction of blood pressure levels after activation could be observed. This treatment option offers maximum adherence to antihypertensive therapy to avoid future cardiovascular end-organ damage and possibly reduce antihypertensive medication and undesirable side effects. PMID- 27184292 TI - Frequency of RHD variants in Brazilian blood donors from Parana State, Southern Brazil. AB - The Rh blood group system is one of the most complex, polymorphic and immunogenic blood group systems in humans. Some individuals produce a weak or a partial D as a result of RHD and RHCE gene conversion events and RHD point mutations. Because the incidence of RHD variants differs considerably among ethnic groups, the objective of this study was to establish the frequency of blood donors carrying some weak and partial RHD, at the molecular level, in 400 blood donors from the North/Northwest of the state of Parana, Southern Brazil. Another 30 blood donors whose RhD typing results in serology were inconclusive were also included. In this mixed Brazilian population, the most frequent weak D types were 1, 4, 3 and 2 (frequencies of 4.35%, 2.32%, 1.46% and 0.29%, respectively; total of 8.41%) and partial D was found in 2.90% of samples carrying the RHD gene. For samples with inconclusive RhD typing, 53.33% of them presented weak and partial RHD, and 43.75% had concomitantly more than one RHD variant. Our results demonstrate the presence of Caucasian and African D variants. This knowledge can contribute to the safety of transfusion strategies in this ethnic admixture population. PMID- 27184291 TI - Spatial organization of heterologous metabolic system in vivo based on TALE. AB - For years, prokaryotic hosts have been widely applied in bio-engineering. However, the confined in vivo enzyme clustering of heterologous metabolic pathways in these organisms often results in low local concentrations of enzymes and substrates, leading to a low productive efficacy. We developed a new method to accelerate a heterologous metabolic system by integrating a transcription activator-like effector (TALE)-based scaffold system into an Escherichia coli chassis. The binding abilities of the TALEs to the artificial DNA scaffold were measured through ChIP-PCR. The effect of the system was determined through a split GFP study and validated through the heterologous production of indole-3 acetic acid (IAA) by incorporating TALE-fused IAA biosynthetic enzymes in E. coli. To the best of our knowledge, we are the first to use the TALE system as a scaffold for the spatial organization of bacterial metabolism. This technique might be used to establish multi-enzymatic reaction programs in a prokaryotic chassis for various applications. PMID- 27184293 TI - Does microbial contamination influence the success of the hematopoietic cell transplantation outcomes? AB - INTRODUCTION: Microbial contamination can be a marker for faulty process and is assumed to play an important role in the collection of hematopoietic progenitor cell (HPC) and infusion procedure. We aimed to determine the microbial contamination rates and evaluate the success of hematopoietic cell transplantation (HCT) in patients who received contaminated products. PATIENTS METHODS: We analyzed microbial contamination records of HPC grafts between 2012 and 2015, retrospectively. Contamination rates of autologous donors were evaluated for at three steps: at the end of mobilization, following processing with dimethyl sulfoxide, and just before stem cell infusion. Grafts of allogeneic donors were assessed only before HCT. RESULT: A total of 445 mobilization procedures were carried out on 333 (167 autologous and 166 allogeneic) donors. The microbiological contamination of peripheral blood (323/333 donations) and bone marrow (10/333 donations) products were analyzed. Bacterial contamination was detected in 18 of 1552 (1.15 %) culture bottles of 333 donors. During the study period 248 patients underwent HCT and among these patients microbial contamination rate on sample basis was 1.3 % (16/1212). Microbial contamination detected in nine patients (7 autologous; 2 allogeneic). In 8 of 9 patients, a febrile neutropenic attack was observed. The median day for the neutropenic fever was 4 days (0-9). None of the patients died within the post-transplant 30 days who received contaminated products. CONCLUSION: The use of contaminated products with antibiotic prophylaxis may be safe in terms of the first day of fever, duration of fever, neutrophil, platelet engraftment and duration of hospitalization. PMID- 27184296 TI - The effect of dietary Chlorella vulgaris supplementation on micro-organism community, enzyme activities and fatty acid profile in the rumen liquid of goats. AB - Microalgae might be considered as an alternative source of fat and/or protein for ruminant's diets. However, changes in populations of ruminal micro-organisms associated with biohydrogenation process, methane and ammonia production in response to microalgae dietary supplementation have not been well characterized. Thus, 16 cross-bred goats were divided into two groups. Each goat of both groups was fed individually with alfalfa hay and concentrates separately. The concentrates of the control group had no microalgae while those of the treated group were supplemented with 10 g lyophilized Chlorella vulgaris/kg concentrate (chlor). On the 30th experimental day, samples of rumen fluid were collected for microbial DNA extraction, fatty acid profile and enzyme activity analyses. The results showed that the chlor diet compared with the control increased significantly the populations of Methanosphaera stadtmanae, Methanobrevibacter ruminantium and Methanogens bacteria and protozoa in the rumen of goats. A significant reduction in the cellulase activity and in the abundance of Ruminococcus albus, and a significant increase in the protease activity and in the abundance of Clostridium sticklandii in the rumen liquid of goats fed with the chlor diet, compared with the control, were found. Chlorella vulgaris supplementation promoted the formation of trans C18:1 , trans-11 C18:1 and monounsaturated fatty acids (MUFA), while the proportions of C18:0 and long-chain fatty acids (LCFA) reduced significantly in the rumen liquid of goats. This shift in ruminal biohydrogenation pathway was accompanied by a significant increase in Butyrivibrio fibrisolvens trans C18:1 -producing bacteria. In conclusion, the supplementation of diets with microalgae needs further investigation because it enhances the populations of methane-producing bacteria and protozoa. PMID- 27184295 TI - Single administration of soluble epoxide hydrolase inhibitor suppresses neuroinflammation and improves neuronal damage after cardiac arrest in mice. AB - Cardiac arrest (CA) causes ischemia-reperfusion injury in the whole body among victims. Especially in the brain, inflammation and neuronal cell death can lead to irreversible dysfunction. Our goal was to determine whether a single administration of soluble epoxide hydrolase inhibitor (AS2586144-CL) has a neuroprotective effect and decreases the inflammatory response after CA and cardiopulmonary resuscitation (CPR). Global cerebral ischemia was induced in male C57BL/6 mice with 8min of CA. Thirty minutes after recovery of spontaneous circulation, the mice were randomly assigned to three groups and administered AS2586144-CL: 1mg/kg (n=25), 10mg/kg (n=25), or 0mg/kg (vehicle, n=25). At 6 and 7 days after CA/CPR, behavioral tests were conducted and brains were removed for histological evaluation. Analysis of histological damage 7 days after CA/CPR revealed that 10mg/kg of AS2586144-CL protected neurons, and suppressed cytokine production and microglial migration into the hippocampus. Two hours after CA/CPR, 10mg/kg of AS2586144-CL suppressed serum tumor necrosis factor-alpha and hippocampal nuclear factor kappaB expression. Our data show that 10mg/kg of AS2586144-CL administered following CA/CPR suppresses inflammation and decreases neuronal damage. PMID- 27184294 TI - A novel "complement-metabolism-inflammasome axis" as a key regulator of immune cell effector function. AB - The inflammasomes are intracellular multiprotein complexes that induce and regulate the generation of the key pro-inflammatory cytokines IL-1beta and IL-18 in response to infectious microbes and cellular stress. The activation of inflammasomes involves several upstream signals including classic pattern or danger recognition systems such as the TLRs. Recently, however, the activation of complement receptors, such as the anaphylatoxin C3a and C5a receptors and the complement regulator CD46, in conjunction with the sensing of cell metabolic changes, for instance increased amino acid influx and glycolysis (via mTORC1), have emerged as additional critical activators of the inflammasome. This review summarizes recent advances in our knowledge about complement-mediated inflammasome activation, with a specific focus on a novel "complement - metabolism - NLRP3 inflammasome axis." PMID- 27184297 TI - The efficacy of attention bias modification therapy in cocaine use disorders. AB - BACKGROUND: Attentional bias (i.e., differences in reaction time between drug and neutral cues) has been associated with a variety of drug-use behaviors (e.g., craving, abstinence). Reduction of bias may ultimately reduce use. OBJECTIVE: The current study examined whether attentional bias modification therapy (ABMT) reduced the frequency of drug use behaviors in individuals with cocaine use disorder (CUD). METHOD: Participants (n = 37) were randomly assigned to ABMT or control therapy, which systematically varied how frequently probes replaced neutral (ABMT = 100%; control therapy = 50%) relative to drug stimuli. Each intervention included 5 training sessions comprising a total of 2640 trials over 4 weeks. Clinical assessments occurred at baseline, post-intervention, 2 weeks and 3 months posttreatment. RESULTS: There were no baseline differences between groups on drug-use behaviors or other clinical measures. Contrary to predictions, both groups exhibited slower rather than faster reaction times for cocaine stimuli (p = 0.005) at baseline, with no relationship between bias and baseline measures of drug-use behavior. CONCLUSIONS: ABMT was not more effective than our control therapy at reducing attentional bias, reducing craving or changing other drug use behaviors. Current results suggest additional replication studies are needed to assess ABMT's efficacy in reducing drug-use behaviors in CUD. PMID- 27184298 TI - In vitro flow cytometry-based screening platform for cellulase engineering. AB - Ultrahigh throughput screening (uHTS) plays an essential role in directed evolution for tailoring biocatalysts for industrial applications. Flow cytometry based uHTS provides an efficient coverage of the generated protein sequence space by analysis of up to 10(7) events per hour. Cell-free enzyme production overcomes the challenge of diversity loss during the transformation of mutant libraries into expression hosts, enables directed evolution of toxic enzymes, and holds the promise to efficiently design enzymes of human or animal origin. The developed uHTS cell-free compartmentalization platform (InVitroFlow) is the first report in which a flow cytometry-based screened system has been combined with compartmentalized cell-free expression for directed cellulase enzyme evolution. InVitroFlow was validated by screening of a random cellulase mutant library employing a novel screening system (based on the substrate fluorescein-di-beta-D cellobioside), and yielded significantly improved cellulase variants (e.g. CelA2 H288F-M1 (N273D/H288F/N468S) with 13.3-fold increased specific activity (220.60 U/mg) compared to CelA2 wildtype: 16.57 U/mg). PMID- 27184300 TI - A Simple Score Model to Assess Prediabetes Risk Status Based on the Medical Examination Data. AB - OBJECTIVES: We aimed to build a risk score model to screen out the patients at high-risk status so as to prevent or delay the conversion of prediabetes to diabetes. METHODS: The population were divided into 2 groups: 1 was an exploratory population, and the other was a validation population. All the data were extracted from the electronic medical examination datasets in the School Hospital of Harbin Institute of Technology, Harbin, China. A binary logistic regression model was used to screen out the risk factors, and the associated risk factors were categorized into 3 levels to create the prediabetes score model. We divided the total score into 4 risk categories: low, middle, high and extremely high risk. We also tested the performance of our prediabetes risk score model. RESULTS: Age, body mass indexes, histories of hypertension, family histories of diabetes, diastolic blood pressure levels and triglyceride levels were screened out as independent risk factors in order to build the risk score model. The area under the curve (AUC) of the prediabetes risk score model was 0.748 (95% CI, 0.720 to 0.777), and the AUC for the validation population reached 0.713 (95% CI, 0.686 to 0.740). Low, middle, high and extremely high risk statuses for prediabetes were associated with a total score of 0 to 3, 4 to 6, 7 to 10 and 11 to 12. CONCLUSIONS: Our prediabetes score model can be used easily and understood by doctors and other related users to assess prediabetes risk status. The intervention program, designed based on our prediabetes score model, is likely to prevent or delay the conversion of prediabetes to diabetes. PMID- 27184299 TI - The Risk for New-Onset Diabetes Mellitus after Kidney Transplantation in Patients with Autosomal Dominant Polycystic Kidney Disease: A Systematic Review and Meta Analysis. AB - OBJECTIVES: New-onset diabetes after kidney transplantation (NODAT) is associated with both renal allograft failure and increased rates of mortality. The objective of this meta-analysis was to evaluate the risk for NODAT in patients with autosomal dominant polycystic kidney disease (ADPKD). METHODS: A literature search was performed using MEDLINE, EMBASE and Cochrane Database of Systematic Reviews from inception through July 2015. Studies that reported relative risks, odd ratios or hazard ratios comparing the risk for NODAT in patients with ADPKD were included. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using a random-effect, generic inverse variance method. RESULTS: Included in the analysis were 12 cohort studies, which comprised 1379 patients with ADPKD of a total of 9849 patients who had undergone kidney transplants. The pooled RRs of NODAT in patients with ADPKD were 1.92 (95% CI, 1.36 to 2.70). When meta-analysis was limited only to studies with confounder-adjusted analysis, the pooled RRs for NODAT were 1.98 (95% CI, 1.33 to 2.94). However, the association between NODAT requiring insulin treatment was insignificant, with pooled RRs of 1.57 (95% CI, 0.75 to 3.27). CONCLUSIONS: Our meta-analysis demonstrates a significant association between ADPKD and NODAT in recipients of kidney transplants. The findings of this study may impact clinical management and follow up for patients with ADPKD after kidney transplantation. PMID- 27184301 TI - Psychiatric and Behavioural Disorders in Children with Epilepsy (ILAE Task Force Report): Epilepsy and autism. AB - A high proportion of children with epilepsy have autism spectrum disorder. Although estimates vary, depending both on the population studied and the definitions used, a figure of around 20% has typically been reported. Autism can have a major impact on the life of the child and family. Despite the importance of this comorbidity and although many studies have been performed, a full understanding of the possible links between epilepsy and autism remains elusive. In a minority of cases, for example in the Landau-Kleffner syndrome, the autistic features can be the result of the epilepsy itself. However, there has been a failure to demonstrate that the epilepsy itself plays a major role in most cases. The current evidence seems to point to a common underlying predisposing factor. The discovery of a growing number of genetic defects leading to both conditions would support this explanation of the link. PMID- 27184302 TI - Bio-recovery of non-essential heavy metals by intra- and extracellular mechanisms in free-living microorganisms. AB - Free-living microorganisms may become suitable models for recovery of non essential and essential heavy metals from wastewater bodies and soils by using and enhancing their accumulating and/or leaching abilities. This review analyzes the variety of different mechanisms developed mainly in bacteria, protists and microalgae to accumulate heavy metals, being the most relevant those involving phytochelatin and metallothionein biosyntheses; phosphate/polyphosphate metabolism; compartmentalization of heavy metal-complexes into vacuoles, chloroplasts and mitochondria; and secretion of malate and other organic acids. Cyanide biosynthesis for extra-cellular heavy metal bioleaching is also examined. These metabolic/cellular processes are herein analyzed at the transcriptional, kinetic and metabolic levels to provide mechanistic basis for developing genetically engineered microorganisms with greater capacities and efficiencies for heavy metal recovery, recycling of heavy metals, biosensing of metal ions, and engineering of metalloenzymes. PMID- 27184304 TI - Blunted blood pressure response during hyperpnoea in endurance runners. AB - The purpose of this study was to elucidate the cardiovascular response during hyperpnoea in endurance-trained runners compared to sedentary controls. Twelve runners and ten sedentary individuals participated in this study. A maximal respiratory endurance test (MRET) was performed as follows: target minute ventilation was initially set at 30% of maximal voluntary ventilation (MVV12) and was increased by 10% MVV12 every 3min. The test was terminated when the subject could no longer maintain the target ventilation. Heart rate and mean arterial blood pressure (MBP) were continuously measured. Respiratory endurance time during the MRET was longer in the runners than the controls. The change in MBP during the MRET was lower in the runners compared to the sedentary controls (runners: 100.2+/-2.4mmHg vs. CONTROLS: 109.1+/-3.0mmHg at 6min of hyperpnoea). Therefore, the blood pressure response during hyperpnoea is blunted in endurance runners, suggesting that whole-body endurance exercise training attenuates the respiratory muscle-induced metaboreflex. PMID- 27184303 TI - Changes in vagal afferent drive alter tracheobronchial coughing in anesthetized cats. AB - Unilateral cooling of the vagus nerve (<5 degrees C, blocking mainly conductivity of myelinated fibers) and unilateral vagotomy were employed to reduce cough afferent drive in order to evaluate the effects of these interventions on the temporal features of the cough reflex. Twenty pentobarbitone anesthetized, spontaneously breathing cats were used. Cough was induced by mechanical stimulation of the tracheobronchial airways. The number of coughs during vagal cooling was significantly decreased (p<0.001). Inspiratory cough efforts were reduced by approximately 30% (p<0.001) and expiratory motor drive by more than 80% (p<0.001). Temporal analysis showed prolonged inspiratory and expiratory phases, the total cycle duration, its active portion, and the interval between maxima of the diaphragm and the abdominal activity during coughing (p<0.001). There was no significant difference in the average effects on the cough reflex between cooling of the left or the right vagus nerve. Compared to control, vagal cooling produced no significant difference in heart rate and mean arterial blood pressure (p>0.05), however, cold block of vagal conduction reduced respiratory rate (p<0.001). Unilateral vagotomy significantly reduced cough number, cough related diaphragmatic activity, and relative values of maximum expiratory esophageal pressure (all p<0.05). Our results indicate that reduced cough afferent drive (lower responsiveness) markedly attenuates the motor drive to respiratory pump muscles during coughing and alters cough temporal features. Differences in the effects of unilateral vagal cooling and vagotomy on coughing support an inhibitory role of sensory afferents that are relatively unaffected by cooling of the vagus nerve to 5 degrees C on mechanically induced cough. PMID- 27184305 TI - Using the decision ladder to understand road user decision making at actively controlled rail level crossings. AB - Rail level crossings (RLXs) represent a key strategic risk for railways worldwide. Despite enforcement and engineering countermeasures, user behaviour at RLXs can often confound expectations and erode safety. Research in this area is limited by a relative absence of insights into actual decision making processes and a focus on only a subset of road user types. One-hundred and sixty-six road users (drivers, motorcyclists, cyclists and pedestrians) completed a diary entry for each of 457 naturalistic encounters with RLXs when a train was approaching. The final eligible sample comprised 94 participants and 248 encounters at actively controlled crossings where a violation of the active warnings was possible. The diary incorporated Critical Decision Method probe questions, which enabled user responses to be mapped onto Rasmussen's decision ladder. Twelve percent of crossing events were non-compliant. The underlying decision making was compared to compliant events and a reference decision model to reveal important differences in the structure and type of decision making within and between road user groups. The findings show that engineering countermeasures intended to improve decision making (e.g. flashing lights), may have the opposite effect for some users because the system permits a high level of flexibility for circumvention. Non-motorised users were more likely to access information outside of the warning signals because of their ability to achieve greater proximity to the train tracks and the train itself. The major conundrum in resolving these issues is whether to restrict the amount of time and information available to users so that it cannot be used for circumventing the system or provide more information to help users make safe decisions. PMID- 27184306 TI - Suitability of virtual prototypes to support human factors/ergonomics evaluation during the design. AB - In recent years, the use of virtual prototyping has increased in product development processes, especially in the assessment of complex systems targeted at end-users. The purpose of this study was to evaluate the suitability of virtual prototyping to support human factors/ergonomics evaluation (HFE) during the design phase. Two different virtual prototypes were used: augmented reality (AR) and virtual environment (VE) prototypes of a maintenance platform of a rock crushing machine. Nineteen designers and other stakeholders were asked to assess the suitability of the prototype for HFE evaluation. Results indicate that the system model characteristics and user interface affect the experienced suitability. The VE system was valued as being more suitable to support the assessment of visibility, reach, and the use of tools than the AR system. The findings of this study can be used as a guidance for the implementing virtual prototypes in the product development process. PMID- 27184308 TI - Quantifying warfighter performance in a target acquisition and aiming task using wireless inertial sensors. AB - An array of inertial measurement units (IMUS) was experimentally employed to analyze warfighter performance on a target acquisition task pre/post fatigue. Eleven participants (5M/6F) repeated an exercise circuit carrying 20 kg of equipment until fatigued. IMUs secured to the sacrum, sternum, and a rifle quantified peak angular velocity magnitude (PAVM) and turn time (TT) on a target acquisition task (three aiming events with two 180 degrees turns) within the exercise circuit. Turning performance of two turns was evaluated pre/post fatigue. Turning performance decreased with fatigue. PAVMs decreased during both turns for the sternum (p < 0.001), sacrum (p = 0.007) and rifle (p = 0.002). TT increased for the sternum (p = 0.001), sacrum (p = 0.003), and rifle (p = 0.02) during turn 1, and for the rifle (p = 0.04) during turn 2. IMUs detected and quantified changes in warfighter aiming performance after fatigue. Similar methodologies can be applied to many movement tasks, including quantifying movement performance for load, fatigue, and equipment conditions. PMID- 27184309 TI - Establishing usability heuristics for heuristics evaluation in a specific domain: Is there a consensus? AB - Heuristics evaluation is frequently employed to evaluate usability. While general heuristics are suitable to evaluate most user interfaces, there is still a need to establish heuristics for specific domains to ensure that their specific usability issues are identified. This paper presents a comprehensive review of 70 studies related to usability heuristics for specific domains. The aim of this paper is to review the processes that were applied to establish heuristics in specific domains and identify gaps in order to provide recommendations for future research and area of improvements. The most urgent issue found is the deficiency of validation effort following heuristics proposition and the lack of robustness and rigour of validation method adopted. Whether domain specific heuristics perform better or worse than general ones is inconclusive due to lack of validation quality and clarity on how to assess the effectiveness of heuristics for specific domains. The lack of validation quality also affects effort in improving existing heuristics for specific domain as their weaknesses are not addressed. PMID- 27184307 TI - Obesity-related changes in prolonged repetitive lifting performance. AB - Despite the rising prevalence of obesity, little is known about its moderating effects on injury risk factors, such as fatigue, in occupational settings. This study investigated the effect of obesity, prolonged repetitive lifting and their interaction on lifting performance of 14 participants, 7 obese (mean body mass index (BMI): 33.2 kg m(-2)) and 7 non-obese (mean BMI: 22.2 kg m(-2)) subjects. To present a physically challenging task, subjects performed repetitive lifting for 1 h at 120% of their maximum acceptable weight of lift. Generalized linear mixed models were fit to posture and acceleration data. The obese group bent to a ~10 degrees lower peak trunk sagittal flexion angle, had 17% lower root mean square (RMS) jerk and took 0.8 s longer per lift. Over time, the obese group increased their trunk transverse and sagittal posterior accelerations while the non-obese maintained theirs. Although the majority of lifting variables were unaffected by BMI or its interaction with prolonged lifting duration, the observed differences, combined with a greater upper body mass, necessitate a more cautious use of existing psychophysical lifting limits for individuals who are obese, particularly when fatigued. PMID- 27184310 TI - Using kinematic reduction for studying grasping postures. An application to power and precision grasp of cylinders. AB - The kinematic analysis of human grasping is challenging because of the high number of degrees of freedom involved. The use of principal component and factorial analyses is proposed in the present study to reduce the hand kinematics dimensionality in the analysis of posture for ergonomic purposes, allowing for a comprehensive study without losing accuracy while also enabling velocity and acceleration analyses to be performed. A laboratory study was designed to analyse the effect of weight and diameter in the grasping posture for cylinders. This study measured the hand posture from six subjects when transporting cylinders of different weights and diameters with precision and power grasps. The hand posture was measured using a Vicon((r)) motion-tracking system, and the principal component analysis was applied to reduce the kinematics dimensionality. Different ANOVAs were performed on the reduced kinematic variables to check the effect of weight and diameter of the cylinders, as well as that of the subject. The results show that the original twenty-three degrees of freedom of the hand were reduced to five, which were identified as digit arching, closeness, palmar arching, finger adduction and thumb opposition. Both cylinder diameter and weight significantly affected the precision grasping posture: diameter affects closeness, palmar arching and opposition, while weight affects digit arching, palmar arching and closeness. The power-grasping posture was mainly affected by the cylinder diameter, through digit arching, closeness and opposition. The grasping posture was largely affected by the subject factor and this effect couldn't be attributed only to hand size. In conclusion, this kinematic reduction allowed identifying the effect of the diameter and weight of the cylinders in a comprehensive way, being diameter more important than weight. PMID- 27184311 TI - Route complexity and simulated physical ageing negatively influence wayfinding. AB - The aim of this age-simulation field experiment was to assess the influence of route complexity and physical ageing on wayfinding. Seventy-five people (aged 18 28) performed a total of 108 wayfinding tasks (i.e., 42 participants performed two wayfinding tasks and 33 performed one wayfinding task), of which 59 tasks were performed wearing gerontologic ageing suits. Outcome variables were wayfinding performance (i.e., efficiency and walking speed) and physiological outcomes (i.e., heart and respiratory rates). Analysis of covariance showed that persons on more complex routes (i.e., more floor and building changes) walked less efficiently than persons on less complex routes. In addition, simulated elderly participants perform worse in wayfinding than young participants in terms of speed (p < 0.001). Moreover, a linear mixed model showed that simulated elderly persons had higher heart rates and respiratory rates compared to young people during a wayfinding task, suggesting that simulated elderly consumed more energy during this task. PMID- 27184312 TI - Why we love or hate our cars: A qualitative approach to the development of a quantitative user experience survey. AB - This paper presents a more ecologically valid way of developing theory-based item questionnaires for measuring user experience. In this novel approach, items were generated using natural and domain-specific language of the research population, what seems to have made the survey much more sensitive to real experiences than theory-based ones. The approach was applied in a survey that measured car experience. Ten in-depth interviews were conducted with drivers inside their cars. The resulting transcripts were analysed with the aim of capturing their natural utterances for expressing their car experience. This analysis resulted in 71 categories of answers. For each category, one sentence was selected to serve as a survey-item. In an online platform, 538 respondents answered the survey. Data reliability, tested with Cronbach alpha index, was 0.94, suggesting a survey with highly reliable results to measure drivers' appraisals of their cars. PMID- 27184313 TI - Corrigendum to "Working postures and physical activity among registered nurses" [Appl. Ergon. 54 (2016), 243-250]. PMID- 27184314 TI - Standing on a declining surface reduces transient prolonged standing induced low back pain development. AB - While alternating standing position on a sloped surface has proven successful at reducing low back pain during standing, the purpose of this study was to evaluate standing solely on a declining surface to isolate the influence of the postural change. Seventeen participants performed two 75-min prolonged standing occupational simulations- level ground and declining surface. Fifty-three percent of participants (9/17) were categorized as pain developers during the level ground standing condition. For these same pain developers, their average maximum pain scores were 58% lower during sloped standing. All participants showed greater hip flexion, trunk-to-thigh angle flexion, and posterior translation of the trunk center of gravity when standing on the sloped surface. These postural changes could cause the muscles crossing the hip posteriorly to increase passive stiffness and assist with stabilizing the pelvis. This study stresses the importance of hip kinematics, not just lumbar spine posture, in reducing prolonged standing induced low back pain. PMID- 27184315 TI - Occupational sitting behaviour and its relationship with back pain - A pilot study. AB - Nowadays, working in an office environment is ubiquitous. At the same time, progressively more people suffer from occupational musculoskeletal disorders. Therefore, the aim of this pilot study was to analyse the influence of back pain on sitting behaviour in the office environment. A textile pressure mat (64-sensor matrix) placed on the seat pan was used to identify the adopted sitting positions of 20 office workers by means of random forest classification. Additionally, two standardised questionnaires (Korff, BPI) were used to assess short and long-term back pain in order to divide the subjects into two groups (with and without back pain). Independent t-test indicated that subjects who registered back pain within the last 24 h showed a clear trend towards a more static sitting behaviour. Therefore, the developed sensor system has successfully been introduced to characterise and compare sitting behaviour of subjects with and without back pain. PMID- 27184316 TI - Maintaining knife sharpness in industrial meat cutting: A matter of knife or meat cutter ability. AB - Knife sharpness is imperative in meat cutting. The aim of this study was to compare the impact of knife blade steel quality with meat cutters' individual ability to maintain the cutting edge sharp in an industrial production setting. Twelve meat cutters in two different companies using three different knives during normal production were studied in this quasi-experimental study. Methods included were measuring knife cutting force before and after knife use, time knives were used, ratings of sharpness and discomfort and interviews. Results showed that the meat cutters' skill of maintaining sharpness during work had a much larger effect on knife sharpness during work than the knife steel differences. The ability was also related to feelings of discomfort and to physical exertion. It was found that meat cutters using more knives were more likely to suffer from discomfort in the upper limbs, which is a risk for developing MSD. PMID- 27184317 TI - Effects of elevation change on mental stress in high-voltage transmission tower construction workers. AB - High-voltage transmission tower construction is a high-risk operation due to the construction site locations, extreme climatic factors, elevated working surfaces, and narrow working space. To comprehensively enhance our understanding of the psychophysiological phenomena of workers in extremely high tower constructions, we carried out a series of field experiments to test and compare three working surface heights in terms of frequency-domain heart rate variability (HRV) measurements. Twelve experienced male workers participated in this experiment. The dependent variables, namely, heart rate (HR), normalized low-frequency power (nLF), normalized high-frequency power (nHF), and LF-to-HF power ratio (LF/HF), were measured with the Polar RS800CX heart rate monitor. The experimental results indicated that the task workload was similar between working surface heights. Tower construction workers perceived an increased level of mental stress as working surface height increased. PMID- 27184318 TI - Using archetypes to create user panels for usability studies: Streamlining focus groups and user studies. AB - Designers at the conceptual phase of products such as headphones, stress the importance of comfort, e.g. executing comfort studies and the need for a reliable user panel. This paper proposes a methodology to issue a reliable user panel to represent large populations and validates the proposed framework to predict comfort factors, such as physical fit. Data of 200 heads was analyzed by forming clusters, 9 archetypal people were identified out of a 200 people's ear database. The archetypes were validated by comparing the archetypes' responses on physical fit against those of 20 participants interacting with 6 headsets. This paper suggests a new method of selecting representative user samples for prototype testing compared to costly and time consuming methods which relied on the analysis of human geometry of large populations. PMID- 27184319 TI - Iterative user centered design for development of a patient-centered fall prevention toolkit. AB - Due to the large number of falls that occur in hospital settings, inpatient fall prevention is a topic of great interest to patients and health care providers. The use of electronic decision support that tailors fall prevention strategy to patient-specific risk factors, known as Fall T.I.P.S (Tailoring Interventions for Patient Safety), has proven to be an effective approach for decreasing hospital falls. A paper version of the Fall T.I.P.S toolkit was developed primarily for hospitals that do not have the resources to implement the electronic solution; however, more work is needed to optimize the effectiveness of the paper version of this tool. We examined the use of human factors techniques in the redesign of the existing paper fall prevention tool with the goal of increasing ease of use and decreasing inpatient falls. The inclusion of patients and clinical staff in the redesign of the existing tool was done to increase adoption of the tool and fall prevention best practices. The redesigned paper Fall T.I.P.S toolkit showcased a built in clinical decision support system and increased ease of use over the existing version. PMID- 27184320 TI - Constitutive kinematic modes and shapes during vehicle ingress/egress. AB - A study was undertaken to investigate the kinematics of older users of passenger vehicles during ingress/egress and to seek correlations between their movement and comfort rating assigned by the subjects to the ease of vehicle ingress and egress. A principal component analysis was performed on the subjects' kinematics to identify the underlying modes of movement employed by the subjects. It was found that a small number of modes could describe the movements of all the subjects across all of the vehicles. Within the subspace defined by the modal vectors, shapes were found which correlated to the comfort rating for ease of ingress and egress which the subjects had assigned to each of the cars. Knowledge of these shapes which correspond to good and poor ingress and egress will be useful to the designers of interiors and exteriors of passenger vehicles for the older person. It is recommended that vehicle designs for the older person should attempt to avoid body positions which require excessive ankle articulation and lumbar flexion/extension during ingress and egress. PMID- 27184321 TI - Evaluation of overhead guide sign sheeting materials to increase visibility and safety for drivers. AB - Overhead guide sign visibility must increase to improve driver safety on roadways. Two methods increase overhead guide sign visibility: sign illumination and use of retroreflective sheeting materials. This paper compares three types of retroreflective sheeting: Engineering Grade (type I), Diamond Grade (type XI), and High Intensity (type IV). A field experiment was conducted at night using licensed drivers to determine the optimum retroreflective sheeting material that increases sign visibility and legibility. Results showed that, of the three types of retroreflective sheeting, Diamond Grade (type XI) sheeting requires minimum illuminance to be visible, followed by High Intensity (type IV) sheeting. Cost analysis, including labor, maintenance, and material cost components of the three retroreflective sheeting materials, showed that High Intensity (type IV) could increase sign visibility and legibility at night for Departments of Transportation with limited budgets, consequently increasing driver safety on roadways. PMID- 27184322 TI - Thermo-physiological comfort of soft-shell back protectors under controlled environmental conditions. AB - The aim of the study was to investigate thermo-physiological comfort of three back protectors identifying design features affecting heat loss and moisture management. Five volunteers tested the back protectors in a climatic chamber during an intermittent physical activity. Heart rate, average skin temperature, sweat production, microclimate temperature and humidity have been monitored during the test. The sources of heat losses have been identified using infrared thermography and the participants answered a questionnaire to express their subjective sensations associated with their thermo-physiological condition. The results have shown that locally torso skin temperature and microclimate depended on the type of back protector, whose design allowed different extent of perspiration and thermal insulation. Coupling physiological measurements with the questionnaire, it was found that overall comfort was dependent more on skin wetness than skin temperature: the participants preferred the back protector with the highest level of ventilation through the shell and the lowest level of microclimate humidity. PMID- 27184324 TI - Improving the detectability of oxygen saturation level targets for preterm neonates: A laboratory test of tremolo and beacon sonifications. AB - Recent guidelines recommend oxygen saturation (SpO2) levels of 90%-95% for preterm neonates on supplemental oxygen but it is difficult to discern such levels with current pulse oximetry sonifications. We tested (1) whether adding levels of tremolo to a conventional log-linear pulse oximetry sonification would improve identification of SpO2 ranges, and (2) whether adding a beacon reference tone to conventional pulse oximetry confuses listeners about the direction of change. Participants using the Tremolo (94%) or Beacon (81%) sonifications identified SpO2 range significantly more accurately than participants using the LogLinear sonification (52%). The Beacon sonification did not confuse participants about direction of change. The Tremolo sonification may have advantages over the Beacon sonification for monitoring SpO2 of preterm neonates, but both must be further tested with clinicians in clinically representative scenarios, and with different levels of ambient noise and distractions. PMID- 27184323 TI - Effects of indoor slippers on plantar pressure and lower limb EMG activity in older women. AB - Open-toe mule slippers are popular footwear worn at home especially by older women. However, their biomechanical effects are still poorly understood. The objective of this study is to therefore evaluate the physical properties of two typical types of open-toe mule slippers and the changes in plantar pressure and lower limb muscle activity of older women when wearing these slippers. Five walking trials have been carried out by ten healthy women. The results indicate that compared to barefoot, wearing slippers results in significant increases in the contact area of the mid-foot regions which lead to plantar pressure redistribution from metatarsal heads 2-3 and the lateral heel to the midfoot regions. However, there is no significant difference in the selected muscle activity across all conditions. The findings enhance our understanding of slipper features associated with changes in biomechanical measures thereby providing the basis of slipper designs for better foot protection and comfort. PMID- 27184325 TI - Evaluating the low back biomechanics of three different office workstations: Seated, standing, and perching. AB - The objective of this study was to evaluate how different workstations may influence physical behavior in office work through motion and how that may affect spinal loads and discomfort. Twenty subjects performed a typing task in three different workstations (seated, standing, and perching) for one hour each. Measures of postural transitions, spinal loads, discomfort, and task performance were assessed in order to understand the effects of workstation interaction over time. Results indicated that standing had the most amount of motion (6-8 shifts/min), followed by perching (3-7 shifts/min), and then seating (<1 shift/min). Standing had the highest reports of discomfort and seating the least. However, spinal loads were highest in A/P shear during standing (190N posterior shear, 407N anterior shear) compared to perching (65N posterior shear, 288N anterior shear) and seating (106N posterior shear, 287 anterior shear). These loads are below the risk threshold for shear, but may still elicit a cumulative response. Perching may induce motion through supported mobility in the perching stool, whereas standing motion may be due to postural discomfort. Office workstation designs incorporating supported movement may represent a reasonable trade-off in the costs-benefits between seating and standing. PMID- 27184326 TI - Intervention development to reduce musculoskeletal disorders: Is the process on target? AB - Work related musculoskeletal disorders remain an intractable OHS problem. In 2002, Haslam proposed applying the stage of change model to target ergonomics interventions and other health and safety prevention activities. The stage of change model proposes that taking into account an individual's readiness for change in developing intervention strategies is likely to improve uptake and success. This paper revisits Haslam's proposal in the context of interventions to reduce musculoskeletal disorders. Effective MSD interventions require a systematic approach and need to take into account a combination of measures. Research evidence suggests that in practice, those charged with the management of MSDs are not consistently adopting such an approach. Consequently, intervention development may not represent contemporary best practice. We propose a potential method of addressing this gap is the stage of change model, and use a case study to illustrate this argument in tailoring intervention development for managing MSDs. PMID- 27184327 TI - Patient acuity as a determinant of paramedics' frequency of being exposed to physically demanding work activities. AB - BACKGROUND: The purpose of this investigation was to examine if paramedics' frequency of being exposed to highly physically demanding activities, or their perception of physical, clinical, and emotional demands were altered by patients' acuity level, operationalized using the Canadian Triage and Acuity Scale (CTAS). METHODS: Physical demands descriptions (PDD) were compiled from thirteen services across Canada. The observation sessions took place during a minimum of two full shift (12-h) ride-outs at each service. Data were obtained from 53 ride-outs, which included a total of 190 calls. RESULTS: Higher urgency calls (CTAS level I or II) required significantly more stretcher handling, equipment handling, and intravenous (IV) work, also prompting higher ratings of perceived clinical, physical, and emotional demand. Independent of CTAS level, stretcher loading with patient (15.0%), horizontal patient transfer (13.7%), and pushing/pulling the stretcher with patient (13.1%) were identified as the most physically demanding tasks. CONCLUSIONS: Patient acuity is an important determinant affecting the frequency for which paramedics are exposed to work tasks with inherent ergonomic hazards (e.g., handling a stretcher with a patient). Patient acuity also affects paramedics' perceived clinical, physical, and emotional demands of a call. PMID- 27184328 TI - The relationship between air layers and evaporative resistance of male Chinese ethnic clothing. AB - In this study, the air layer distribution and evaporative resistances of 39 sets of male Chinese ethnic clothing were investigated using a sweating thermal manikin and the three-dimensional (3D) body scanning technique. Relationships between the evaporative resistance and air layers (i.e., air gap thickness and air volume) were explored. The results demonstrated that the clothing total evaporative resistance increases with the increasing air gap size/air volume, but the rate of increase gradually decreases as the mean air gap size or the total air volume becomes larger. The clothing total evaporative resistance reaches its maximum when the average air gap size and the total air volume are 41.6 mm and 69.9 dm(3), respectively. Similar general trends were also found between local mean air gap size and clothing local evaporative resistance at different body parts. However, different body parts show varied rates of increase and decrease in the local evaporative resistance. The research findings provide a comprehensive database for predicting overall and local human thermal comfort while wearing male Chinese ethnic clothing. PMID- 27184329 TI - Associations between shift schedule characteristics with sleep, need for recovery, health and performance measures for regular (semi-)continuous 3-shift systems. AB - In this cross-sectional study associations were examined between eight shift schedule characteristics with shift-specific sleep complaints and need for recovery and generic health and performance measures. It was hypothesized that shift schedule characteristics meeting ergonomic recommendations are associated with better sleep, need for recovery, health and performance. Questionnaire data were collected from 491 shift workers of 18 companies with 9 regular (semi) continuous shift schedules. The shift schedule characteristics were analyzed separately and combined using multilevel linear regression models. The hypothesis was largely not confirmed. Relatively few associations were found, of which the majority was in the direction as expected. In particular early starts of morning shifts and many consecutive shifts seem to be avoided. The healthy worker effect, limited variation between included schedules and the cross-sectional design might explain the paucity of significant results. PMID- 27184331 TI - Bifurcation and temporal periodic patterns in a plant-pollinator model with diffusion and time delay effects. AB - This paper deals with a plant-pollinator model with diffusion and time delay effects. By considering the distribution of eigenvalues of the corresponding linearized equation, we first study stability of the positive constant steady state and existence of spatially homogeneous and spatially inhomogeneous periodic solutions are investigated. We then derive an explicit formula for determining the direction and stability of the Hopf bifurcation by applying the normal form theory and the centre manifold reduction for partial functional differential equations. Finally, we present an example and numerical simulations to illustrate the obtained theoretical results. PMID- 27184330 TI - Epilepsy is not a mandatory feature of STXBP1 associated ataxia-tremor retardation syndrome. AB - BACKGROUND: Mutations in the STXBP1 gene (MUNC18-1) were first described to cause Ohtahara syndrome (Early infantile epileptic encephalopathy, EIEE)(12-14) characterized by very early infantile epileptic encephalopathy with frequent tonic spasms and a suppression-burst pattern on electroencephalogram. In the following years a wider phenotype was recognized having milder forms of epilepsies. All patients showed also intellectual disability and movement disorders. METHODS: Here, we present three female patients with an ataxia-tremor retardation syndrome caused by a de novo STXBP1 mutation. Two of the girls were diagnosed through next-generation-sequencing as mutations in STXBP1 were not suspected. The third patient was diagnosed by targeted genetic testing due to its clinical features strikingly similar to the first two girls. RESULTS: The characteristic feature of our three patients is the lack of epilepsy which is in contrast to the majority of the patients with STXBP1 mutation. CONCLUSION: Hence, epilepsy is not a mandatory feature of patients with a STXBP1 mutation. PMID- 27184332 TI - Development of a 4D numerical chest phantom with customizable breathing. AB - Respiratory movement information is useful for radiation therapy, and is generally obtained using 4D scanners (4DCT). In the interest of patient safety, reducing the use of 4DCT could be a significant step in reducing radiation exposure, the effects of which are not well documented. The authors propose a customized 4D numerical phantom representing the organ contours. Firstly, breathing movement can be simulated and customized according to the patient's anthroporadiametric data. Using learning sets constituted by 4D scanners, artificial neural networks can be trained to interpolate the lung contours corresponding to an unknown patient, and then to simulate its respiration. Lung movement during the breathing cycle is modeled by predicting the lung contours at any respiratory phases. The interpolation is validated comparing the obtained lung contours with 4DCT via Dice coefficient. Secondly, a preliminary study of cardiac and oesophageal motion is also presented to demonstrate the flexibility of this approach. The application may simulate the position and volume of the lungs, the oesophagus and the heart at every phase of the respiratory cycle with a good accuracy: the validation of the lung modeling gives a Dice index greater than 0.93 with 4DCT over a breath cycle. PMID- 27184333 TI - Illuminating the dark side of recycling endosomes. PMID- 27184335 TI - Corrigendum. PMID- 27184334 TI - The SRF-YAP-IL6 axis promotes breast cancer stemness. PMID- 27184336 TI - Corrigendum. PMID- 27184337 TI - Comment on Lapaj et al.: Retrieval analysis of titanium nitride (TiN) coated prosthetic femoral heads articulating with polyethylene. PMID- 27184338 TI - The synthesis of size-controlled 3C-SiC nanoflakes and their photoluminescent properties. AB - Size-controlled and high-purity 3C-SiC nanoflakes (NFs) are synthesized on the tips of vertically aligned carbon nanotube (VA-CNT) carpets with a hot-filament chemical vapor deposition (HF-CVD) method. The average diameter and height of SiC NFs can be tuned by changing the thickness of per-deposited Si and growth conditions. The growth process of the SiC NFs is suggested to be dominated by a vapor-solid (VS) mechanism. The prepared SiC NFs exhibit quantum-confinement effects, emitting strong violet-blue photoluminescence (PL) under ultraviolet excitation. The PL peak position changes from 410 to 416 nm as the excitation line increases from 290 to 400 nm. This result opens the possibility for the application of the luminescent solid-state freestanding 3C-SiC NFs in photonics as well as photonics/electronics integration. PMID- 27184341 TI - Evolution of larval life mode of Oecophoridae (Lepidoptera: Gelechioidea) inferred from molecular phylogeny. AB - Phylogenetic relationships within family Oecophoridae have been poorly understood. Consequently the subfamily and genus level classifications with this family problematic. A comprehensive phylogenetic analysis of Oecophoridae, the concealer moths, was performed based on analysis of 4444 base pairs of mitochondrial COI, nuclear ribosomal RNA genes (18S and 28S) and nuclear protein coding genes (IDH, MDH, Rps5, EF1a and wingless) for 82 taxa. Data were analyzed using maximum likelihood (ML), parsimony (MP) and Bayesian (BP) phylogenetic frameworks. Phylogenetic analyses indicated that (i) genera Casmara, Tyrolimnas and Pseudodoxia did not belong to Oecophoridae, suggesting that Oecophoridae s. authors was not monophyletic; (ii) other oecophorids comprising two subfamilies, Pleurotinae and Oecophorinae, were nested within the same clade, and (iii) Martyringa, Acryptolechia and Periacmini were clustered with core Xyloryctidae. They appeared to be sister lineage with core Oecophoridae. BayesTraits were implemented to explore the ancestral character states to infer historical microhabitat patterns and sheltering strategy of larvae. Reconstruction of ancestral microhabitat of oecophorids indicated that oecophorids might have evolved from dried plant feeders and further convergently specialized. The ancestral larva sheltering strategy of oecophorids might have used a silk tube by making itself, shifting from mining leaves. PMID- 27184340 TI - Workplace psychosocial and organizational factors for neck pain in workers in the United States. AB - BACKGROUND: Neck pain is a prevalent musculoskeletal condition among workers in the United States. This study explores a set of workplace psychosocial and organization-related factors for neck pain. METHODS: Data used for this study come from the 2010 National Health Interview Survey which provides a representative sample of the US population. To account for the complex sampling design, the Taylor linearized variance estimation method was used. Logistic regression models were constructed to measure the associations. RESULTS: This study demonstrated significant associations between neck pain and a set of workplace risk factors, including work-family imbalance, exposure to a hostile work environment and job insecurity, non-standard work arrangements, multiple jobs, and long work hours. CONCLUSION: Workers with neck pain may benefit from intervention programs that address issues related to these workplace risk factors. Future studies exploring both psychosocial risk factors and physical risk factors with a longitudinal design will be important. Am. J. Ind. Med. 59:549-560, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27184339 TI - Investigating the Impact of a Genome-Wide Supported Bipolar Risk Variant of MAD1L1 on the Human Reward System. AB - Recent genome-wide association studies have identified MAD1L1 (mitotic arrest deficient-like 1) as a susceptibility gene for bipolar disorder and schizophrenia. The minor allele of the single-nucleotide polymorphism (SNP) rs11764590 in MAD1L1 was associated with bipolar disorder. Both diseases, bipolar disorder and schizophrenia, are linked to functional alterations in the reward system. We aimed at investigating possible effects of the MAD1L1 rs11764590 risk allele on reward systems functioning in healthy adults. A large homogenous sample of 224 young (aged 18-31 years) participants was genotyped and underwent functional magnetic resonance imaging (fMRI). All participants performed the 'Desire-Reason Dilemma' paradigm investigating the neural correlates that underlie reward processing and active reward dismissal in favor of a long-term goal. We found significant hypoactivations of the ventral tegmental area (VTA), the bilateral striatum and bilateral frontal and parietal cortices in response to conditioned reward stimuli in the risk allele carriers compared with major allele carriers. In the dilemma situation, functional connectivity between prefrontal brain regions and the ventral striatum was significantly diminished in the risk allele carriers. Healthy risk allele carriers showed a significant deficit of their bottom-up response to conditioned reward stimuli in the bilateral VTA and striatum. Furthermore, functional connectivity between the ventral striatum and prefrontal areas exerting top-down control on the mesolimbic reward system was reduced in this group. Similar alterations in reward processing and disturbances of prefrontal control mechanisms on mesolimbic brain circuits have also been reported in bipolar disorder and schizophrenia. Together, these findings suggest the existence of an intermediate phenotype associated with MAD1L1. PMID- 27184344 TI - A case of puerperal group a streptococcal sepsis complicated by ovarian vein thrombosis. PMID- 27184342 TI - Number of metastatic lymph nodes as determinant of outcome after salvage radical prostatectomy for radiation-recurrent prostate cancer. AB - BACKGROUND: Presence of lymph node metastasis (LNM) at salvage radical prostatectomy (sRP) is associated with poor outcome. Predictors of outcome in this context remain undetermined. ThE objective was to assess the role of number of positive lymph node on outcome of patients with LNM after sRP and for radio recurrent prostate cancer. MATERIAL AND METHODS: We analyzed data from a consecutive cohort of 215 men treated with sRP at a single institution. We used univariate Cox proportional hazard regression models for biochemical recurrence (BCR) and metastatic outcomes, with prostate-specific antigen, Gleason score, extraprostatic extension, seminal vesicle invasion, time between radiation therapy and sRP, and number of positive nodes as predictors. RESULTS: Of the 47 patients with LNM, 37 developed BCR, 11 developed distant metastasis and 4 died with a median follow-up of 2.3 years for survivors. The risk of metastases increased with higher pre-operative PSA levels (HR 1.19 per 1ng/ml; 95% CI: 1.06 1.34; P=.003). The remaining predictors did not reach conventional levels of significance. However, removal of 3 or more positive lymph nodes demonstrated a positive association, as expected, with metastatic disease (HR 3.44; 95% CI: 0.91 13.05; P=.069) compared to one or 2 positive nodes. Similarly, the presence of extraprostatic extension, seminal vesicle invasion and Gleason grade greater than 7 also demonstrated a positive association with higher risk of metastasis, with hazard ratios of 3.97 (95% CI: 0.50, 31.4; P=.2), 3.72 (95% CI: 0.80-17.26; P=.1), and 1.45 (95% CI: 0.44-4.76; P=.5), respectively. CONCLUSIONS: In patients with LNM after sRP for radio-recurrent prostate cancer, the risk of distant metastasis is likely to be influenced by the number of positive nodes (3 or more), high preoperative PSA, Gleason grade and advanced pathologic stage. These results are consistent with the findings of number of nodes (1 to 2 vs. 3 or more nodes positive) as a prognostic indicator after primary radical prostatectomy and strengthen the plea for a revision of the nodal staging for prostate cancer. PMID- 27184343 TI - Motivating parents of kids with asthma to quit smoking: the effect of the teachable moment and increasing intervention intensity using a longitudinal randomized trial design. AB - AIMS: We tested two aims: (1) the teachable moment (TM): whether second-hand smoke exposure (SHSe) feedback motivates cessation in parents of children with asthma versus parents of healthy children (HC); and (2) whether greater intervention intensity [enhanced-precaution adoption model (PAM)] produces greater cessation than a previously tested intervention (PAM). DESIGN AND INTERVENTIONS: Aim 1: two home visits (asthma education or child wellness), and cessation induction using motivational interviewing and SHSe feedback. Aim 2: post-home-visits, parents with asthmatic children were randomized to PAM (n = 171; six asthma education calls) or enhanced-PAM (n = 170; six asthma education/smoking cessation calls + repeat SHSe feedback). SETTING: Rhode Island, USA. PARTICIPANTS: Parents of asthmatic (n = 341) or healthy (n = 219) children who did not have to want to quit smoking to enroll. MEASUREMENTS: Measurements were given at baseline, 2, 4, 6 and 12 months. Abstinence was bioverified. Outcomes were 7-day and 30-day point prevalence abstinence (ppa) and SHSe (primary) and asthma morbidity (secondary). FINDINGS: Aim 1: the TM was supported: parents of asthmatic children were more than twice as likely to achieve 30-day [odds ratio (OR) = 2.60, 95% confidence interval (CI) = 1.22-5.54] and 7-day ppa (OR = 2.26, 95% CI = 1.13-4.51) at 2 months (primary end-point) and have non-detectable levels of SHSe than HCs. Greater treatment intensity yielded stronger TM effects (OR = 3.60; 95% CI = 1.72-7.55). Aim 2: enhanced-PAM was more likely to achieve 30-day ppa at the primary end-point, 4 months (OR = 2.12, 95% CI 1.09-4.12) and improved asthma outcomes versus PAM. CONCLUSIONS: Smoking cessation intervention (Motivational Interviewing plus biomarker feedback) appear to motivate smoking cessation more strongly among parents of asthmatic children than among parents of healthy children. Increased intervention intensity yields greater smoking cessation among parents of asthmatic children and better asthma outcomes. PMID- 27184345 TI - A neutron spectrum unfolding code based on generalized regression artificial neural networks. AB - The most delicate part of neutron spectrometry, is the unfolding process. The derivation of the spectral information is not simple because the unknown is not given directly as a result of the measurements. Novel methods based on Artificial Neural Networks have been widely investigated. In prior works, back propagation neural networks (BPNN) have been used to solve the neutron spectrometry problem, however, some drawbacks still exist using this kind of neural nets, i.e. the optimum selection of the network topology and the long training time. Compared to BPNN, it's usually much faster to train a generalized regression neural network (GRNN). That's mainly because spread constant is the only parameter used in GRNN. Another feature is that the network will converge to a global minimum, provided that the optimal values of spread has been determined and that the dataset adequately represents the problem space. In addition, GRNN are often more accurate than BPNN in the prediction. These characteristics make GRNNs to be of great interest in the neutron spectrometry domain. This work presents a computational tool based on GRNN capable to solve the neutron spectrometry problem. This computational code, automates the pre-processing, training and testing stages using a k-fold cross validation of 3 folds, the statistical analysis and the post-processing of the information, using 7 Bonner spheres rate counts as only entrance data. The code was designed for a Bonner Spheres System based on a 6LiI(Eu) neutron detector and a response matrix expressed in 60 energy bins taken from an International Atomic Energy Agency compilation. PMID- 27184346 TI - Antioxidant and Myocardial Preservation Activities of Natural Phytochemicals from Mung Bean (Vigna radiata L.) Seeds. AB - Mung bean (Vigna radiata L.) seeds (MBS) contain abundant nutrients with biological activities. This study was aimed to isolate key bioactive components from MBS with antioxidant and myocardial preservation activities. A new flavonoid C-glycoside, isovitexin-6"-O-alpha-l-glucoside, and 14 known compounds were obtained. Their structures were identified by extensive 1D and 2D NMR and FT-ICR MS spectroscopic analyses. The antioxidant activities of these compounds were evaluated. Compounds 1-5 and 7-10 displayed 2,2'-azinobis (3-ethylbenzothiazoline 6-sulphonic acid) (ABTS(*+)) scavenging activity, but only 5 and 7 exhibited 2,2 diphenyl-1-picrylhydrazyl (DPPH(*)) scavenging activity. The myocardial preservation effect of 2, 3, and MBS were investigated by measuring the serum levels of LDH, CK, and AST as well as the tissue level of MDA and SOD. The results demonstrated that 2, 3, and MBS had a significant protective effect against ISO-induced myocardial ischemia. MBS can be regarded as a potential new source of antioxidants and myocardial preservation agents. PMID- 27184347 TI - Confined placental mosaicism and its impact on confirmation of NIPT results. AB - Non-invasive prenatal testing (NIPT) has been widely used to screen for common aneuploidies since 2011. While NIPT is highly sensitive and specific, false positive results can occur. One important cause of false positive results is confined placental mosaicism (CPM). This can occur through a mitotic nondisjunction event or through aneuploidy rescue. CPM is usually associated with normal fetal outcomes, but has been associated with intrauterine growth restriction, pregnancy loss, or perinatal death in some cases. CPM may also be a marker for uniparental disomy. Given that NIPT can result in false positives, positive results should be confirmed with invasive testing before any irreversible procedure is performed. Whether to perform CVS or amniocentesis to confirm a positive NIPT result is controversial. While CVS can be performed earlier than amniocentesis, CPM can also cause false positive results. Our practice is to proceed with CVS, and to examine all cell lines using both an uncultured sample using fluorescence in situ hybridization (FISH) or short-term culture, as well as long-term culture of the sample. If the results all show aneuploidy, the results are reported to the patient. Otherwise, if the results are also mosaic, amniocentesis is recommended and analyzed by both FISH and karyotype. (c) 2016 Wiley Periodicals, Inc. PMID- 27184349 TI - Light-Modulation of the Charge Injection in a Polymer Thin-Film Transistor by Functionalizing the Electrodes with Bistable Photochromic Self-Assembled Monolayers. AB - High fatigue resistance, bistability, and drastic property changes among isomers allow efficient modulation of the current output of organic thin-film transistors (OTFTs) to be obtained by a photogating of the charge-injection mechanism. PMID- 27184348 TI - Risk factors for unplanned readmission within 30 days after pediatric neurosurgery: a nationwide analysis of 9799 procedures from the American College of Surgeons National Surgical Quality Improvement Program. AB - OBJECTIVE Hospital readmission rate is increasingly used as a quality outcome measure after surgery. The purpose of this study was to establish, using a national database, the baseline readmission rates and risk factors for patient readmission after pediatric neurosurgical procedures. METHODS The American College of Surgeons National Surgical Quality Improvement Program-Pediatric database was queried for pediatric patients treated by a neurosurgeon between 2012 and 2013. Procedures were categorized by current procedural terminology (CPT) code. Patient demographics, comorbidities, preoperative laboratory values, operative variables, and postoperative complications were analyzed via univariate and multivariate techniques to find associations with unplanned readmissions within 30 days of the primary procedure. RESULTS A total of 9799 cases met the inclusion criteria, 1098 (11.2%) of which had an unplanned readmission within 30 days. Readmission occurred 14.0 +/- 7.7 days postoperatively (mean +/- standard deviation). The 4 procedures with the highest unplanned readmission rates were CSF shunt revision (17.3%; CPT codes 62225 and 62230), repair of myelomeningocele > 5 cm in diameter (15.4%), CSF shunt creation (14.1%), and craniectomy for infratentorial tumor excision (13.9%). The lowest unplanned readmission rates were for spine (6.5%), craniotomy for craniosynostosis (2.1%), and skin lesion (1.0%) procedures. On multivariate regression analysis, the odds of readmission were greatest in patients experiencing postoperative surgical site infection (SSI; deep, organ/space, superficial SSI, and wound disruption: OR > 12 and p < 0.001 for each). Postoperative pneumonia (OR 4.294, p < 0.001), urinary tract infection (OR 4.262, p < 0.001), and sepsis (OR 2.616, p = 0.006) also independently increased the readmission risk. Independent patient risk factors for unplanned readmission included Native American race (OR 2.363, p = 0.019), steroid use > 10 days (OR 1.411, p = 0.010), oxygen supplementation (OR 1.645, p = 0.010), nutritional support (OR 1.403, p = 0.009), seizure disorder (OR 1.250, p = 0.021), and longer operative time (per hour increase, OR 1.059, p = 0.029). CONCLUSIONS This study may aid in identifying patients at risk for unplanned readmission following pediatric neurosurgery, potentially helping to focus efforts at lowering readmission rates, minimizing patient risk, and lowering costs for health care systems. PMID- 27184350 TI - Panobinostat consolidation in patients with Hodgkin lymphoma at risk for relapse after high dose chemotherapy and autologous stem cell transplant: final results after early trial discontinuation. PMID- 27184351 TI - Effects of alpha-Thalassemia on HbA1c Measurement. AB - BACKGROUND: alpha-Thalassemia is a benign condition that is often present in patients with diabetes mellitus. Here, we evaluated the effects of different genotypes alpha-thalassemia on HbA1c measurement. METHODS: A total of 189 samples from nondiabetic patients were analyzed. HbA1c analysis was performed by ion exchange high-performance liquid chromatography, boronate affinity HPLC, immunoassay, and capillary electrophoresis. Fasting glucose, fructosamin, and HbA2 were also performed. All samples were confirmed by genotyping for thalassemia. RESULTS: In patients with two or three functional alpha-genes, HbA1c values were not significantly different from those of controls (P > 0.05); however, in individuals with alpha-thalassemia with one functional alpha-gene (i.e., HbH disease), HbA1c levels were significantly different from those of controls (P < 0.01). HbA1c values were significantly lower in individuals with HbH disease than in control individuals and patients in the other two alpha thalassemia groups. For patients with HbH disease, there were no significant differences in the four HbA1c measurement systems (P > 0.05). CONCLUSIONS: In this study, HbA1c values in samples from individuals with two or three functional alpha-genes basically reflected the normal mean blood glucose level, while those in samples from individuals with one functional alpha-gene did not. PMID- 27184352 TI - Osseous Metaplasia of the Breast Diagnosed from Stereotactic Core Biopsy: A Rare Entity with Radiologic-Pathologic Correlation. PMID- 27184353 TI - Clinical outcome and paravalvular leakage of the new balloon-expandable Edwards Sapien 3 valve in comparison to its predecessor model (Edwards Sapien XT) in patients undergoing transfemoral aortic valve replacement. AB - OBJECTIVES: The aim of this study was to compare the 30-day procedural, clinical and echocardiographic outcome of the new balloon-expandable Edwards Sapien 3 (ES3) valve with the Edwards Sapien XT (ESXT). BACKGROUND: Post-implant paravalvular leaks (PVL) after transfemoral aortic valve replacement (TAVR) resulting in residual aortic regurgitation (AR) are a major limitation for long term outcome. New TAVR-devices have to eliminate this problem. METHODS: Transfemoral TAVR was performed in 209 consecutive intermediate-high-risk surgical patients (pts) with symptomatic aortic stenosis (ESXT n = 102, ES3 n = 107). Transthoracic echocardiography (TTE) and 3-dimensional computed tomography were used for valve size selection. Primary endpoint of the study was none/trace AR derived by TTE 30-days after TAVR. RESULTS: All pts underwent successfully TAVR with a combined device success of 100/102 (99%) in ESXT and 107/107 (100%) in ES3 pts. Fluoroscopy time (ESXT 11.8 +/- 0.5 min vs. ES3 10.0 +/- 0.5 min, P = 0.003) and contrast (ESXT 188.9 +/- 5.6 mL vs. ES3 170.4 +/- 4.7 mL, P = 0.04) were significantly lower in ES3 patients. 30-day clinical events did not differ. Transvalvular mean pressure gradients were significantly reduced to 7.4 +/- 0.8 mmHg after ESXT and to 10.1+/- 0.4 mmHg after ES3 implantation. After 30 days none/trace AR was found in 34.3% (n = 35) of all ESXT pts in contrast to 89.7% (n = 96) of all ES3 patients. Moderate-to-severe AR was found rarely (ESXT 2.9% vs. ES3 0%, P = 0.073). CONCLUSIONS: Although there was no significant difference in 30 day mortality, the newer ES3 valve reduced significantly residual paravalvular leakage. (c) 2016 Wiley Periodicals, Inc. PMID- 27184354 TI - Mandibular incisive canal in Han Chinese using cone beam computed tomography. AB - The aim of this study was to provide reference information for implantology and chin bone harvesting in people of Han Chinese ethnicity by studying the mandibular incisive canal (MIC) using cone beam computed tomography (CBCT). Fifty subjects were included in the study. CBCT scans were obtained for all subjects, and 22 also underwent panoramic radiography to evaluate the visibility of the MIC. The CBCT data of the 50 subjects were reconstructed to measure MIC diameter, length, and location within the mandible. A MIC was identified in 38.6% of panoramic radiographs, with good clarity in 13.6%, while a MIC was identified in 100% of CBCT images, with good clarity in 63.6%. The diameter of the MIC decreased from origin to end. The left and right average MIC lengths were 17.84mm and 17.73mm, respectively. The MIC was close to the buccal cortical border and lower margin of the mandible. In conclusion, the MIC is an anatomical structure in the mandible that can be identified reliably with CBCT. On insertion, implants should be inclined slightly towards the lingual aspect of the anterior mandible to protect the MIC. The chin bone harvesting depth should be limited to 4mm; the harvesting site can be adjusted to the region above or below the MIC. PMID- 27184355 TI - Norovirus (NoV) specific protective immune responses induced by recombinant P dimer vaccine are enhanced by the mucosal adjuvant FlaB. AB - BACKGROUND: Noroviruses (NoVs) are a major cause of childhood gastroenteritis and foodborne diseases worldwide. Lack of appropriate animal models or cell-based culture systems makes the development and evaluation of NoV-specific vaccines a daunting task. VP1 is the major capsid protein of the NoVs that acts as a binding motif to human histo-blood group antigens (HBGAs) through its protruding 2 (P2) domain and can serve as a protective antigen candidate for vaccine development. METHODS: Recombinantly produced NoV specific P domain (Pd) vaccine was inoculated into groups of mice either alone or in conjugation with mucosal adjuvant FlaB, the flagellar protein from Vibrio vulnificus. Antigen specific humoral and cell mediated immune responses were assessed by enzyme linked immunosorbent assay (ELISA) or fluorescent activated cell sorting (FACS). A comparative analysis of various routes of vaccination viz. intranasal, sublingual and subcutaneous, was also done. RESULTS: In this study, we show that a recombinant Pd-vaccine administered through intranasal route induced a robust TH2-dependent humoral immune response and that the combination of vaccine with FlaB significantly enhanced the antibody response. Interestingly, FlaB induced a mixed TH1/TH2 type of immune response with a significant induction of IgG1 as well as IgG2a antibodies. FlaB also induced strong IgA responses in serum and feces. FlaB mediated antibody responses were toll like receptor 5 (TLR5) dependent, since the FlaB adjuvanticity was lost in TLR5(-/-) mice. Further, though the Pd-vaccine by itself failed to induce a cell mediated immune response, the Pd-FlaB combination stimulated a robust CD4(+)IFNgamma(+) and CD8(+)IFNgamma(+) T cell response in spleen and mesenteric lymph nodes. We also compared the adjuvant effects of FlaB with that of alum and complete Freund's adjuvant (CFA). We found that subcutaneously inoculated FlaB induced more significant levels of IgG and IgA in both serum and feces compared to alum or CFA in respective samples. CONCLUSION: We validate the use of TLR5 agonist as a strong mucosal adjuvant that would facilitate the development of NoV specific vaccines for humans and veterinary use. This study also highlights the importance of route of immunization in inducing the appropriate immune responses in mucosal compartments. PMID- 27184357 TI - Disorders of Sex Development-Ambiguous Genitalia. PMID- 27184358 TI - Palladium-catalysed directed C-H activation by anilides and ureas; water participation in a general base mechanism. AB - C-H activation plays a central role in organometallic catalysis. Concerted metallation-deprotonation (CMD) has been dominant as the pathway for C-H bond cleavage. In the course of studying the mechanism of C-H activation of arylamides and arylureas with Pd complexes as part of catalytic oxidative Heck reactions, DFT calculations were carried out. The turnover-limiting C-H activation is acid catalysed and can occur readily in the absence of acetate or other coordinating bases. The calculations simulated experiment, so that ligated sulfonate and water, both previously observed by X-ray characterization, were incorporated in the model. A Wheland-type complex between acetanilide and Pd was readily located, but the reactive C-H and the coordinated sulfonate were poorly placed for intramolecular proton transfer. Involvement of a water molecule coordinated to sulfonate provides a low-energy pathway to the palladacycle. The relative reactivity of substituted acetanilides and arylureas according to this model fits well with existing literature. General-base catalysis as described here has broader potential. PMID- 27184356 TI - Adolescent Sleep and the Impact of Technology Use Before Sleep on Daytime Function. AB - Technology has become pervasive in our culture, particularly among adolescents. The purpose of this study is to examine associations between use of technology before sleep and daytime function in adolescents. DESIGN AND METHODS: This study is a secondary analysis of respondents aged 13 to 21 years (N = 259) from the 2011 National Sleep Foundation's Sleep in America Poll. The survey included questions on demographics, sleep habits, and use of technology in the hour before bedtime. Daytime sleepiness was assessed with the Epworth Sleepiness Scale (ESS). Student's t-tests, Mann-Whitney U, and Fischer's exact tests were performed to detect differences in demographics, sleep duration, and technology use in the total sample, and between respondents with "adequate" compared to "inadequate" sleep. Correlations were calculated between technology frequency and daytime function. RESULTS: Adolescents had mean sleep duration of 7.3 +/- 1.3 h. Almost all respondents (97%) used some form of technology before sleep. Increased technology use and the frequency of being awoken in the night by a cell phone were significantly associated with waking too early, waking unrefreshed, and daytime sleepiness (p < 0.05). Adolescents who reported "inadequate" sleep had shorter sleep duration, greater frequency of technology use before bedtime, feeling unrefreshed on waking, and greater daytime sleepiness than those reporting "adequate" sleep (all p-values < 0.05). CONCLUSION: Technology use before sleep by adolescents had negative consequences on nighttime sleep and on daytime function. PRACTICE IMPLICATIONS: Healthcare professionals who interact with adolescents should encourage technology to be curtailed before bedtime and for adolescents to value obtaining adequate sleep. PMID- 27184360 TI - Surface-modified Ba(Zr0.3Ti0.7)O3 nanofibers by polyvinylpyrrolidone filler for poly(vinylidene fluoride) composites with enhanced dielectric constant and energy storage density. AB - Ferroelectric-relaxor behavior of Ba(Zr0.3Ti0.7)O3 nanofibers (BZT NF) with a large aspect ratio were prepared via electrospinning and surface modified by PVP as dielectric fillers. The nanocomposite flexible films based on surface modified BZT NF and polyvinylidene fluoride (PVDF) were fabricated via a solution casting. The results show that the surface-modified BZT NF fillers are highly dispersed and well integrated in the PVDF nanocomposites. The nanocomposites exhibit enhanced dielectric constant and reduced loss tangents at a low volume fraction of surface-modified BZT NF. The polymer nanocomposites maintain a relatively high breakdown strength, which is favorable for enhancing energy storage density in the nanocomposites. The nanocomposite containing of 2.5 vol. % of PVP modified BZT NF exhibits energy density as high as 6.3 J/cm(3) at 3800 kV/cm, which is more than doubled that of the pure PVDF of 2.8 J/cm(3) at 4000 kV/cm. Such significant enhancement could be attributed to the combined effects of the surface modification and large aspect ratio of the BZT NF. This work may provide a route for using the surface modified ferroelectric-relaxor behavior of ceramic nanofibers to enhance the dielectric energy density in ceramic-polymer nanocomposites. PMID- 27184359 TI - Relationship between body fat and BMI in a US hispanic population-based cohort study: Results from HCHS/SOL. AB - OBJECTIVE: To evaluate the percentage of body fat (%BF)-BMI relationship, identify %BF levels corresponding to adult BMI cut points, and examine %BF-BMI agreement in a diverse Hispanic/Latino population. METHODS: %BF by bioelectrical impedance analysis was corrected against %BF by (18) O dilution in 434 participants of the ancillary Hispanic Community Health Study/Study of Latinos. Corrected %BF was regressed against 1/BMI in the parent study (n = 15,261), fitting models for each age group, by sex, and Hispanic/Latino background; predicted %BF was then computed for each BMI cut point. RESULTS: Bioelectrical impedance analysis underestimated %BF by 8.7 +/- 0.3% in women and 4.6 +/- 0.3% in men (P < 0.0001). The %BF-BMI relationship was nonlinear and linear for 1/BMI. Sex- and age-specific regression parameters between %BF and 1/BMI were consistent across Hispanic/Latino backgrounds (P > 0.05). The precision of the %BF-1/BMI association weakened with increasing age in men but not women. The proportion of participants classified as nonobese by BMI but as having obesity by %BF was generally higher among women and older adults (16.4% in women vs. 12.0% in men aged 50-74 years). CONCLUSIONS: %BF was linearly related to 1/BMI with consistent relationship across Hispanic/Latino backgrounds. BMI cut points consistently underestimated the proportion of Hispanics/Latinos with excess adiposity. PMID- 27184361 TI - Clinicopathological features and treatment outcomes of the rare, salivary duct carcinoma of parotid gland. AB - BACKGROUND: Salivary ductal carcinoma (SDC) of parotid gland is a rare and aggressive entity; accounting for 1-3 % of all malignant salivary gland tumors, 0.2 % of epithelial salivary gland neoplasms, 0.5 % of salivary gland carcinomas, and 1.1 % of parotid gland carcinomas. Here in we aimed to evaluate the clinico pathological features and treatment outcomes of parotid gland SDC in Saudi population. METHODS: Among 38 patients with parotid malignancies, who were treated in two major tertiary care referral cancer centers between December 2007 and December 2014, seven cases (18.4 %) were found to have SDC, which were investigated for clinicopathological features, locoregional recurrences (LRRs), distant metastasis (DM) and survival rates. RESULTS: Mean age of cohort was 62.3 years (range: 41-83) and female predominant (71.4 %). All patients underwent total parotidectomy and ipsilateral neck dissection. Mean tumor size was 3.4 cm (range: 2.1-5.3); perineural invasion (85.8 %); lymph node involvement (42.9 %); and HER-2 neu overexpression (28.6 %). Postoperative radiation therapy (PORT) was given to six patients (dose: 50-66 Gy). Median follow-up was 20.2 months (range: 11-48). LRRs were seen in five (71.4 %) patients (base of skull, 3 patients; cervical nodes, one patient; parotid bed, one patient). LRRs were salvaged with resection (two patients) and re-irradiation (one patient with base of skull). DM in lungs was seen in three patients (42.8 %); one treated with carboplatin/paclitaxel based chemotherapy. The 4-year disease free and overall survival rates were 16.7 % and 40 % respectively. CONCLUSION: SDC of parotid gland is a rare and aggressive entity, and most of LRRs were seen in the base of skull, which warrants inclusion of base of skull in clinical target volume in PORT planning. Role of anti HER-2 targeted therapy in SDC with HER-2 neu overexpression needs further investigations. PMID- 27184363 TI - CIRSE Standards of Practice Guidelines on Gastrostomy. AB - PURPOSE: Surgical Gastrostomy has been around since the 19th century but in 1980 the first successful percutaneous endoscopic gastrostomy was reported. A year later the first successful percutaneous gastrostomy was performed using fluoroscopic guidance. The technique for percutaneous insertion and the equipment used has been refined since then and it is now considered the gold standard for gastrostomy insertion. Here we present guidelines for image-guided enteral feeding tubes in adults. MATERIAL AND METHOD: We performed a review and analysis of the scientific literature, other national and international guidelines and expert opinion. RESULTS: Studies have shown fluoroscopic techniques have consistently higher success rates with lower rates of major complications than endoscopic techniques. However, the Achilles' heel of many fluoroscopic techniques is the requirement for smaller gastrostomy tube sizes resulting in them being more prone to blockages and thus requiring further intervention. CONCLUSION: Radiological feeding tube insertion is a safe and effective procedure. Success rates are higher, and complication rates lower than PEG or surgical gastrostomy tube placement and innovative techniques for gastric and jejunal access mean that there are very few cases in which RIG is not possible. The principal weakness of radiologically inserted gastrostomies is the limitiation on tube size which leads to a higher rate of tube blockage. Per-oral image-guided gastrostomies have to an extent addressed this but have not been popularised. Currently many centres still consider endoscopic gastrostomies as the first line unless patients are too unwell to undergo this procedure or previous attempts have failed, in which case radioloically inserted gastrostomies are the technique of choice. PMID- 27184362 TI - Global changes in the proteome of Cupriavidus necator H16 during poly-(3 hydroxybutyrate) synthesis from various biodiesel by-product substrates. AB - Synthesis of poly-[3-hydroxybutyrate] (PHB) by Cupriavidus necator H16 in batch cultures was evaluated using three biodiesel-derived by-products as the sole carbon sources: waste glycerol (REG-80, refined to 80 % purity with negligible free fatty acids); glycerol bottom (REG-GB, with up to 65 % glycerol and 35 % free fatty acids), and free fatty acids (REG-FFA, with up to 75 % FFA and no glycerol). All the three substrates supported growth and PHB production by C. necator, with polymer accumulation ranging from 9 to 84 % cell dry weight (cdw), depending on the carbon source. To help understand these differences, proteomic analysis indicated that although C. necator H16 was able to accumulate PHB during growth on all three biodiesel by-products, no changes in the levels of PHB synthesis enzymes were observed. However, significant changes in the levels of expression were observed for two Phasin proteins involved with PHB accumulation, and for a number of gene products in the fatty acid beta-oxidation pathway, the Glyoxylate Shunt, and the hydrogen (H2) synthesis pathways in C. necator cells cultured with different substrates. The glycerol transport protein (GlpF) was induced in REG-GB and REG-80 glycerol cultures only. Cupriavidus necator cells cultured with REG-GB and REG-FFA showed up-regulation of beta-oxidation and Glyoxylate Shunt pathways proteins at 24 h pi, but H2 synthesis pathways enzymes were significantly down-regulated, compared with cells cultured with waste glycerol. Our data confirmed earlier observations of constitutive expression of PHB synthesis proteins, but further suggested that C. necator H16 cells growing on biodiesel-derived glycerol were under oxidative stress. PMID- 27184364 TI - Arteriolymphatic Fistula: An Unusual Cause of Spontaneous Swelling in the Left Supraclavicular Region. AB - An abnormal fistulous communication between an artery and lymphatic system is a rare occurrence. We report a 38-year-old male presenting with sudden onset, spontaneous, pulsatile swelling in the left supraclavicular region following a recent cardiac catheterisation via right femoral arterial access. On evaluation, he was found to have a femoral arteriolymphatic fistula. He was managed conservatively with ultrasound-guided compression with complete resolution of symptoms at follow-up. This case describes a hitherto unknown complication of percutaneous vascular cannulation presenting in an unusual manner, diagnosed with Doppler Ultrasonography and CT angiography and managed effectively with a non invasive therapeutic image-guided manoeuvre. PMID- 27184365 TI - Crystalline-Amorphous-Crystalline Transformation in a Highly Brilliant Luminescent System with Trigonal-Planar Gold(I) Centers. AB - Photoluminescent compounds showing emission color changes in response to external stimuli have received considerable attention because of their wide range of applications. Here, we report the unique photoluminescence behavior of a digold(I) coordination system with trigonal-planar Au(I) centers, [Au2(dppm)3](2+) (dppm = bis(diphenylphosphino)methane). This system shows an extremely intense phosphorescence, with a quantum yield of >95% in the solid state. Both the emission color and thermal stability vary due to changing counter ions (Cl(-) vs. OTf(-)). Of particular note is the thermal crystalline-amorphous crystalline transformation for the chloride salt, which is accompanied by drastic emission color changes. Single-crystal and powder X-ray diffractions demonstrate that the two-step transformation is induced by the loss of water molecules of crystallization with the subsequent removal of a dppm ligand to form [Au2(dppm)2](2+), which is mechanically reverted back to [Au2(dppm)3](2+). PMID- 27184378 TI - Erratum to: Resuscitative endovascular balloon occlusion of the aorta for uncontrolled haemorrahgic shock as an adjunct to haemostatic procedures in the acute care setting. PMID- 27184366 TI - The effect of growth rate on pyrazinamide activity in Mycobacterium tuberculosis insights for early bactericidal activity? AB - BACKGROUND: Pyrazinamide (PZA) plays an essential part in the shortened six-month tuberculosis (TB) treatment course due to its activity against slow-growing and non-replicating organisms. We tested whether PZA preferentially targets slow growing cells of Mycobacterium tuberculosis that could be representative of bacteria that remain after the initial kill with isoniazid (INH), by observing the response of either slow growing or fast growing bacilli to differing concentrations of PZA. METHODS: M. tuberculosis H37Rv was grown in continuous culture at either a constant fast growth rate (Mean Generation Time (MGT) of 23.1 h) or slow growth rate (69.3 h MGT) at a controlled dissolved oxygen tension of 10 % and a controlled acidity at pH 6.3 +/- 0.1. Cultures were exposed to step wise increases in the concentration of PZA (25 to 500 MUgml(-1)) every two MGTs, and bacterial survival was measured. PZA-induced global gene expression was explored for each increase in PZA-concentration, using DNA microarray. RESULTS: At a constant pH 6.3, actively dividing mycobacteria were susceptible to PZA, with similar responses to increasing concentrations of PZA at both growth rates. Three distinct phases of drug response could be distingished for both slow growing (69.3 h MGT) and fast growing (23.1 h MGT) bacilli. A bacteriostatic phase at a low concentration of PZA was followed by a recovery period in which the culture adapted to the presence of PZA and bacteria were actively dividing in steady-state. In contrast, there was a rapid loss of viability at bactericidal concentrations. There was a notable delay in the onset of the recovery period in quickly dividing cells compared with those dividing more slowly. Fast growers and slow growers adapted to PZA-exposure via very similar mechanisms; through reduced gene expression of tRNA, 50S, and 30S ribosomal proteins. CONCLUSIONS: PZA had an equivalent level of activity against fast growing and slow growing M. tuberculosis. At both growth rates drug-tolerance to sub-lethal concentrations may have been due to reduced expression of tRNA, 50S, and 30S ribosomal proteins. The findings from this study show that PZA has utility against more than one phenotypic sub-population of bacilli and could be re-assessed for its early bactericidal activity, in combination with other drugs, during TB treatment. PMID- 27184379 TI - Docetaxel Activity in the Era of Life-prolonging Hormonal Therapies for Metastatic Castration-resistant Prostate Cancer. AB - For >6 yr, docetaxel with prednisone was the only treatment with survival benefits for metastatic castration-resistant prostate cancer (mCRPC). More recently, in clinical practice, abiraterone acetate has been commonly administered prior to docetaxel for the treatment of mCRPC. Our study aimed to review the activity of docetaxel after prior abiraterone. To this end, we analyzed all retrospective reports in the literature describing the overall survival (OS) of mCRPC patients treated with docetaxel after previous abiraterone. The mean OS observed was 12.7 mo, which suggested a significant decrement compared with the 19.2 mo seen in the updated analysis of the TAX 327 study; however, the data are quite similar to the OS of 13.6 mo (95% confidence interval, 12.1-15.1 mo) described in a retrospective single-institution study of 357 men with mCRPC treated with docetaxel with no prior abiraterone mostly in routine practice (86.3%). Because the characteristics of patients recruited in phase 3 trials tend to differ from the real-world setting, we deemed this data set a relevant comparison. Consequently, despite the limitations of retrospective cross-study comparisons, the data suggest that docetaxel retains activity when used as second-line therapy after abiraterone for mCRPC patients. PATIENT SUMMARY: We reviewed the activity of docetaxel after prior use of abiraterone and considered the results in the light of the outcomes of docetaxel used as first line therapy for metastatic castration-resistant prostate cancer (mCRPC) patients in routine practice. We noted that docetaxel retains reasonable activity and is a useful agent for the treatment of mCRPC patients before or after abiraterone. PMID- 27184380 TI - Making Predictive Biomarkers Readily Available. PMID- 27184381 TI - Patient-reported utilities in bilateral visual impairment from amblyopia and age related macular degeneration. AB - BACKGROUND: Utility of visual impairment caused by amblyopia is important for the cost-effectiveness of screening for amblyopia (lazy eye, prevalence 3-3.5 %). We previously measured decrease of utility in 35-year-old persons with unilateral persistent amblyopia. The current observational case-control study aimed to measure loss of utility in patients with amblyopia with recent decrease of vision in their better eye. As these patients are rare, the sample was supplemented by patients with bilateral age-related macular degeneration with similar decrease of vision. METHODS: From our out-patient department, two groups of patients with recent deterioration to bilateral visual acuity less than Snellen 0.5 (bilateral visual impairment, BVI) were recruited, with either persistent amblyopia and age related macular degeneration (AMB + AMD), or with bilateral age-related macular degeneration (BAMD). To measure utility, the time trade-off method and the standard gamble method were applied through interviews. Correlations were sought between utility values and visual acuity, age and Visual Function Questionnaire 25 scores. RESULTS: Seventeen AMB + AMD patients (mean age 72.9 years), and 63 BAMD patients (mean age 79.6 years) were included in the study. Among AMB + AMD, 80 % were willing to trade lifetime in exchange for cure. The overall mean time trade-off utility was 0.925. Among BAMD, 75 % were willing to trade, utility was 0.917. Among AMB + AMD, 38 % accepted risk of death in exchange for cure, overall mean standard gamble utility was 0.999. Among BAMD, 49 % accepted risk of death, utility was 0.998. Utility was not related to visual acuity but it was to age (p = 0.02). CONCLUSION: Elderly patients with BVI, caused by persistent amblyopia and age-related macular degeneration (AMD) or by bilateral AMD, had an approximately 8 % loss of TTO utility. Notably, the 8 % loss in elderly with BVI differs little from the 3.7 % loss we found previously in 35-year-old persons with unilateral amblyopia with good vision in the other eye. The moderate impact of BVI in senescence could be explained by adaptation, comorbidity, avoidance of risk and a changed percept of cure. PMID- 27184382 TI - How do I interpret a confidence interval? AB - A 95% confidence interval (CI) of the mean is a range with an upper and lower number calculated from a sample. Because the true population mean is unknown, this range describes possible values that the mean could be. If multiple samples were drawn from the same population and a 95% CI calculated for each sample, we would expect the population mean to be found within 95% of these CIs. CIs are sensitive to variability in the population (spread of values) and sample size. When used to compare the means of two or more treatment groups, a CI shows the magnitude of a difference between groups. This is helpful in understanding both the statistical significance and the clinical significance of a treatment. In this article we describe the basic principles of CIs and their interpretation. PMID- 27184383 TI - Combined Effects of Acamprosate and Escitalopram on Ethanol Consumption in Mice. AB - BACKGROUND: Major depression is one of the most prevalent psychiatry comorbidities of alcohol use disorders (AUD). As negative emotions can trigger craving and increase the risk of relapse, treatments that target both conditions simultaneously may augment treatment success. Previous studies showed a potential synergistic effect of Food and Drug Administration approved medication for AUD acamprosate and the antidepressant escitalopram. In this study, we investigated the effects of combining acamprosate and escitalopram on ethanol (EtOH) consumption in stress-induced depressed mice. METHODS: Forty singly housed C57BL/6J male mice were subjected to chronic unpredictable stress. In parallel, 40 group-housed male mice were subjected to normal husbandry. After 3 weeks, depressive- and anxiety-like behaviors and EtOH consumption were assessed. For the next 7 days, mice were injected with saline, acamprosate (200 mg/kg; twice/d), escitalopram (5 mg/kg; twice/d), or their combination (n = 9 to 11/drug group/stress group). Two-bottle choice limited-access drinking of 15% EtOH and tap water was performed 3 hours into dark phase immediately after the daily dark phase injection. EtOH drinking was monitored for another 7 days without drug administration. RESULTS: Mice subjected to the chronic unpredictable stress paradigm for 3 weeks showed apparent depression- and anxiety-like behaviors compared to their nonstressed counterparts including longer immobility time in the forced swim test and lower sucrose preference. Stressed mice also displayed higher EtOH consumption and preference in a 2-bottle choice drinking test. During the drug administration period, the escitalopram-only and combined drug groups showed significant reduction in EtOH consumption in nonstressed mice, while only the combined drug group showed significantly reduced consumption in stressed mice. However, such reduction did not persist into the postdrug administration period. CONCLUSIONS: The combination of acamprosate and escitalopram suppressed EtOH intake in both nonstressed and stressed mice; hence, this combination is potentially helpful for AUD individuals with or without comorbid depression to reduce alcohol use. PMID- 27184384 TI - Rivulet: 3D Neuron Morphology Tracing with Iterative Back-Tracking. AB - The digital reconstruction of single neurons from 3D confocal microscopic images is an important tool for understanding the neuron morphology and function. However the accurate automatic neuron reconstruction remains a challenging task due to the varying image quality and the complexity in the neuronal arborisation. Targeting the common challenges of neuron tracing, we propose a novel automatic 3D neuron reconstruction algorithm, named Rivulet, which is based on the multi stencils fast-marching and iterative back-tracking. The proposed Rivulet algorithm is capable of tracing discontinuous areas without being interrupted by densely distributed noises. By evaluating the proposed pipeline with the data provided by the Diadem challenge and the recent BigNeuron project, Rivulet is shown to be robust to challenging microscopic imagestacks. We discussed the algorithm design in technical details regarding the relationships between the proposed algorithm and the other state-of-the-art neuron tracing algorithms. PMID- 27184385 TI - Vitamin-D receptor agonist calcitriol reduces calcification in vitro through selective upregulation of SLC20A2 but not SLC20A1 or XPR1. AB - Vitamin D deficiency (hypovitaminosis D) causes osteomalacia and poor long bone mineralization. In apparent contrast, hypovitaminosis D has been reported in patients with primary brain calcifications ("Fahr's disease"). We evaluated the expression of two phosphate transporters which we have found to be associated with primary brain calcification (SLC20A2, whose promoter has a predicted vitamin D receptor binding site, and XPR1), and one unassociated (SLC20A1), in an in vitro model of calcification. Expression of all three genes was significantly decreased in calcifying human bone osteosarcoma (SaOs-2) cells. Further, we confirmed that vitamin D (calcitriol) reduced calcification as measured by Alizarin Red staining. Cells incubated with calcitriol under calcifying conditions specifically maintained expression of the phosphate transporter SLC20A2 at higher levels relative to controls, by RT-qPCR. Neither SLC20A1 nor XPR1 were affected by calcitriol treatment and remained suppressed. Critically, knockdown of SLC20A2 gene and protein with CRISPR technology in SaOs2 cells significantly ablated vitamin D mediated inhibition of calcification. This study elucidates the mechanistic importance of SLC20A2 in suppressing the calcification process. It also suggests that vitamin D might be used to regulate SLC20A2 gene expression, as well as reduce brain calcification which occurs in Fahr's disease and normal aging. PMID- 27184386 TI - Demographic inference under the coalescent in a spatial continuum. AB - Understanding population dynamics from the analysis of molecular and spatial data requires sound statistical modeling. Current approaches assume that populations are naturally partitioned into discrete demes, thereby failing to be relevant in cases where individuals are scattered on a spatial continuum. Other models predict the formation of increasingly tight clusters of individuals in space, which, again, conflicts with biological evidence. Building on recent theoretical work, we introduce a new genealogy-based inference framework that alleviates these issues. This approach effectively implements a stochastic model in which the distribution of individuals is homogeneous and stationary, thereby providing a relevant null model for the fluctuation of genetic diversity in time and space. Importantly, the spatial density of individuals in a population and their range of dispersal during the course of evolution are two parameters that can be inferred separately with this method. The validity of the new inference framework is confirmed with extensive simulations and the analysis of influenza sequences collected over five seasons in the USA. PMID- 27184388 TI - Murine supraspinatus tendon injury model to identify the cellular origins of rotator cuff healing. AB - : Purpose of this study: To elucidate the origin of cell populations that contribute to rotator cuff healing, we developed a mouse surgical model where a full-thickness, central detachment is created in the supraspinatus. MATERIALS AND METHODS: Three different inducible Cre transgenic mice with Ai9-tdTomato reporter expression (PRG4-9, alphaSMA-9, and AGC-9) were used to label different cell populations in the shoulder. The defect was created surgically in the supraspinatus. The mice were injected with tamoxifen at surgery to label the cells and sacrificed at 1, 2, and 5 weeks postoperatively. Frozen sections were fluorescently imaged then stained with Toluidine Blue and re-imaged. RESULTS: Three notable changes were apparent postoperatively. (1) A long thin layer of tissue formed on the bursal side overlying the supraspinatus tendon. (2) The tendon proximal to the defect initially became hypercellular and disorganized. (3) The distal stump at the insertion underwent minimal remodeling. In the uninjured shoulder, tdTomato expression was seen in the tendon midsubstance and paratenon cell on the bursal side in PRG4-9, in paratenon, blood vessels, and periosteum of acromion in SMA-9, and in articular cartilage, unmineralized fibrocartilage of supraspinatus enthesis, and acromioclavicular joint in AGC-9 mice. In the injured PRG4-9 and SMA-9 mice, the healing tissues contained an abundant number of tdTomato+ cells, while minimal contribution of tdTomato+ cells was seen in AGC-9 mice. CONCLUSIONS: The study supports the importance of the bursal side of the tendon to rotator cuff healing and PRG4 and alphaSMA may be markers for these progenitor cells. PMID- 27184389 TI - Synaptonemal Complex Proteins of Budding Yeast Define Reciprocal Roles in MutSgamma-Mediated Crossover Formation. AB - During meiosis, crossover recombination creates attachments between homologous chromosomes that are essential for a precise reduction in chromosome ploidy. Many of the events that ultimately process DNA repair intermediates into crossovers during meiosis occur within the context of homologous chromosomes that are tightly aligned via a conserved structure called the synaptonemal complex (SC), but the functional relationship between SC and crossover recombination remains obscure. There exists a widespread correlation across organisms between the presence of SC proteins and successful crossing over, indicating that the SC or its building block components are procrossover factors . For example, budding yeast mutants missing the SC transverse filament component, Zip1, and mutant cells missing the Zip4 protein, which is required for the elaboration of SC, fail to form MutSgamma-mediated crossovers. Here we report the reciprocal phenotype-an increase in MutSgamma-mediated crossovers during meiosis-in budding yeast mutants devoid of the SC central element components Ecm11 or Gmc2, and in mutants expressing a version of Zip1 missing most of its N terminus. This novel phenotypic class of SC-deficient mutants demonstrates unequivocally that the tripartite SC structure is dispensable for MutSgamma-mediated crossover recombination in budding yeast. The excess crossovers observed in SC central element-deficient mutants are Msh4, Zip1, and Zip4 dependent, clearly indicating the existence of two classes of SC proteins-a class with procrossover function(s) that are also necessary for SC assembly and a class that is not required for crossover formation but essential for SC assembly. The latter class directly or indirectly limits MutSgamma-mediated crossovers along meiotic chromosomes. Our findings illustrate how reciprocal roles in crossover recombination can be simultaneously linked to the SC structure. PMID- 27184387 TI - Neuroimaging the Effectiveness of Substance Use Disorder Treatments. AB - Neuroimaging techniques to measure the function and biochemistry of the human brain such as positron emission tomography (PET), proton magnetic resonance spectroscopy ((1)H MRS), and functional magnetic resonance imaging (fMRI), are powerful tools for assessing neurobiological mechanisms underlying the response to treatments in substance use disorders. Here, we review the neuroimaging literature on pharmacological and behavioral treatment in substance use disorder. We focus on neural effects of medications that reduce craving (e.g., naltrexone, bupropion hydrochloride, baclofen, methadone, varenicline) and that improve cognitive control (e.g., modafinil, N-acetylcysteine), of behavioral treatments for substance use disorders (e.g., cognitive bias modification training, virtual reality, motivational interventions) and neuromodulatory interventions such as neurofeedback and transcranial magnetic stimulation. A consistent finding for the effectiveness of therapeutic interventions identifies the improvement of executive control networks and the dampening of limbic activation, highlighting their values as targets for therapeutic interventions in substance use disorders. PMID- 27184392 TI - Letter to the Editor: "Comparing the Volume of Brain Metastases in F-18-FET-PET and MRI". PMID- 27184393 TI - Erratum. PMID- 27184394 TI - May 2016 Editor-in-Chief Letter. PMID- 27184391 TI - Clinico-radiological features of primary lacrimal gland pleomorphic adenoma: an analysis of 37 cases. AB - PURPOSE: To present the radiological and clinical features of primary lacrimal gland pleomorphic adenoma (PLGPA). METHODS: Thirty-seven consecutive PLGPAs presenting to two hospitals in Japan were reviewed. RESULTS: PLGPA cases had 15 men and 22 women with a mean age of 51.9 years. Common presenting features were ptosis (83 %), diplopia (78 %) and globe displacement (78 %). Twenty-two percent of cases reported symptom duration of less than 6 months, but only 5.6 % of cases had pain. Sixteen percent of PLGPAs were centered in the palpebral lobe; none of which were associated with globe indentation or lacrimal fossa expansion. Bony excavation was observed in 84 % of orbital lobe PLGPA; the bone margin was well demarcated and the character of excavation was more frequently smooth than scalloped (2:1). The presence of globe indentation or bony excavation was associated with increased tumor size (p = 0.003). An enhancing rim was visible on T1-weighted fat-suppressed gadolinium-enhanced magnetic resonance imaging (T1FS Gad MRI) in 27 %. Five (19 %) enclosed cystic spaces were bright on T2-weighted MRI and non-enhancing. Calcification of tumor parenchyma was common in cystic cases but rare in non-cystic cases (p = 0.01). CONCLUSIONS: PLGPAs have varied clinical and radiological features. Common radiological features are a heterogeneous internal architecture on T2-weighted MRI, an enhancing rim on T1FS Gad MRI, smooth or scalloped bony excavation with intact cortical bone, and globe indentation. Cystic spaces, calcification, and symptom duration less than 6 months are common, but pain is rare. Awareness of the clinico-radiological variants of PLGPA is important when considering incisional biopsy of a lacrimal gland mass. PMID- 27184395 TI - The up-rise in e-cigarette use - friend or foe? PMID- 27184390 TI - Roles for the Histone Modifying and Exchange Complex NuA4 in Cell Cycle Progression in Drosophila melanogaster. AB - Robust and synchronous repression of E2F-dependent gene expression is critical to the proper timing of cell cycle exit when cells transition to a postmitotic state. Previously NuA4 was suggested to act as a barrier to proliferation in Drosophila by repressing E2F-dependent gene expression. Here we show that NuA4 activity is required for proper cell cycle exit and the repression of cell cycle genes during the transition to a postmitotic state in vivo However, the delay of cell cycle exit caused by compromising NuA4 is not due to additional proliferation or effects on E2F activity. Instead NuA4 inhibition results in slowed cell cycle progression through late S and G2 phases due to aberrant activation of an intrinsic p53-independent DNA damage response. A reduction in NuA4 function ultimately produces a paradoxical cell cycle gene expression program, where certain cell cycle genes become derepressed in cells that are delayed during the G2 phase of the final cell cycle. Bypassing the G2 delay when NuA4 is inhibited leads to abnormal mitoses and results in severe tissue defects. NuA4 physically and genetically interacts with components of the E2F complex termed D: rosophila, R: bf, E: 2F A: nd M: yb/ M: ulti-vulva class B: (DREAM/MMB), and modulates a DREAM/MMB-dependent ectopic neuron phenotype in the posterior wing margin. However, this effect is also likely due to the cell cycle delay, as simply reducing Cdk1 is sufficient to generate a similar phenotype. Our work reveals that the major requirement for NuA4 in the cell cycle in vivo is to suppress an endogenous DNA damage response, which is required to coordinate proper S and G2 cell cycle progression with differentiation and cell cycle gene expression. PMID- 27184396 TI - Bactericidal Activity of Usnic Acid-Loaded Electrospun Fibers. AB - BACKGROUND: Usnic acid has been progressively reported in the literature as one of the most important lichen metabolites characterized by a rich diversity of applications such as antifungal, antimicrobial, antiprotozoal and antiviral agent. Particularly, antimicrobial activity of usnic acid can be improved by encapsulation of active molecules in enteric electrospun fibers, allowing the controlled release of active molecule at specific pH. Few relevant patents to the topic have been reviewed and cited. METHODS: Bactericidal activity of usnic acid loaded electrospun fibers of Eudragit L-100 and polyvinylpyrrolidone was examined against Staphylococcus aureus using inhibition hales methodology. RESULTS: The controlled release of active material at high pH is established after 10 minutes of interaction with media and results in reasonable activity against S. aureus, as detected by inhibition hales. CONCLUSION: The strong biological activity of usnic acid-loaded electrospun fibers provides a promising application for corresponding material as a bactericidal agent for wound healing treatment. PMID- 27184398 TI - Poor Feeding, Weight Loss, and Electrolyte Abnormalities in a Term Infant. PMID- 27184397 TI - Pain management among Dominican patients with advanced osteoarthritis: a qualitative study. AB - BACKGROUND: Advanced osteoarthritis and total joint replacement (TJR) recovery are painful experiences and often prompt opioid use in developed countries. Physicians participating in the philanthropic medical mission Operation Walk Boston (OpWalk) to the Dominican Republic have observed that Dominican patients require substantially less opioid medication following TJR than US patients. We conducted a qualitative study to investigate approaches to pain management and expectations for postoperative recovery in patients with advanced arthritis undergoing TJR in the Dominican Republic. METHODS: We interviewed 20 patients before TJR about their pain coping mechanisms and expectations for postoperative pain management and recovery. Interviews were conducted in Spanish, translated, and analyzed in English using content analysis. RESULTS: Patients reported modest use of pain medications and limited knowledge of opioids, and many relied on non pharmacologic therapies and family support to cope with pain. They held strong religious beliefs that offered them strength to cope with chronic arthritis pain and prepare for acute pain following surgery. Patients exhibited a great deal of trust in powerful others, expecting God and doctors to cure their pain through surgery. CONCLUSION: We note the importance of understanding a patient's individual pain coping mechanisms and identifying strategies to support these coping behaviors in pain management. Such an approach has the potential to reduce the burden of chronic arthritis pain while limiting reliance on opioids, particularly for patients who do not traditionally utilize powerful analgesics. PMID- 27184400 TI - Highly sensitive analysis of polycyclic aromatic hydrocarbons in environmental water with porous cellulose/zeolitic imidazolate framework-8 composite microspheres as a novel adsorbent coupled with high-performance liquid chromatography. AB - In this work, novel cellulose/zeolitic imidazolate frameworks-8 composite microspheres have been successfully fabricated and utilized as sorbent for environmental polycyclic aromatic hydrocarbons efficient extraction and sensitive analysis. The composite microspheres were synthesized through the in situ hydrothermal growth of zeolitic imidazolate frameworks-8 on cellulose matrix, and exhibited favorable hierarchical structure with chemical composition as assumed through scanning electron microscopy, Fourier transform infrared spectroscopy, X ray diffraction patterns, and Brunauer-Emmett-Teller surface areas characterization. A robust and highly efficient method was then successfully developed with as-prepared composite microspheres as novel solid-phase extraction sorbent with optimum extraction conditions, such as sorbent amount, sample volume, extraction time, desorption conditions, volume of organic modifier, and ionic strength. The method exhibited high sensitivity with low limit of detection down to 0.1-1.0 ng/L and satisfactory linearity with correlation coefficients ranging from 0.9988 to 0.9999, as well as good recoveries of 66.7-121.2% with relative standard deviations less than 10% for environmental polycyclic aromatic hydrocarbons analysis. Thus, our method was convenient and efficient for polycyclic aromatic hydrocarbons extraction and detection, potential for future environmental water samples analysis. PMID- 27184399 TI - Guideline Recommended Medical Therapy for Cardiovascular Diseases in the Obese: Insights From the Veterans Affairs Clinical Assessment, Reporting, and Tracking (CART) Program. AB - BACKGROUND: Stigma against the obese is well described in health care and may contribute to disparities in medical decision-making. It is unknown whether similar disparity exists for obese patients in cardiovascular care. We evaluated the association between body mass index (BMI) and prescription of guideline recommended medications in patients undergoing elective percutaneous coronary intervention. METHODS AND RESULTS: Using data from the Veterans Affairs Clinical Assessment, Reporting, and Tracking System Program, we identified patients undergoing elective percutaneous coronary intervention from 2007 to 2012, stratifying them by category of BMI. We described rates of prescription for class I guideline recommended medications for each BMI category (normal, overweight, and obese). Multivariable logistic regression assessed the association between BMI category and medication prescription. Seventeen thousand thirty-seven patients were identified, with 35.3% having overweight BMI, and 50.8% obese BMI. Obese patients were more likely than normal BMI patients to be prescribed beta blockers (OR 1.34), statins (OR 1.39), or ACE/ARB (odds ratio [OR] 1.52; all significant) when indicated. Overweight patients were more likely than normal BMI patients to be prescribed statins (OR 1.29) and angiotensin-converting enzymes/angiotensin II receptor blockers (OR 1.41) when indicated. There was no association between BMI category and prescription of anticoagulants. CONCLUSIONS: Over 85% of patients undergoing elective percutaneous coronary intervention in the Veterans Affairs are overweight or obese. Rates of guideline-indicated medication prescription were <70% among all patients, and across BMI categories, with an association between increased BMI and greater use of guideline recommended medications. Our findings offer a possible contribution to the obesity paradox seen in many cardiovascular conditions. PMID- 27184402 TI - Carapace surface architecture facilitates camouflage of the decorator crab Tiarinia cornigera. AB - This paper elucidates the unique setal morphology of the decorator crab Tiarinia cornigera, and further presents evidence to that setal morphology promotes micro organism nucleation and adhesion. The carapace of this crab is covered by clusters of setae, each comprising a hollow acicular stem that is enveloped by a haystack-like structure. Using computational fluid dynamics, we find that these setae are responsible for manipulating water flow over the carapace surface. Micro-organisms in the sea water, nest in areas of flow stagnation and as a result, nucleate to and biofoul the setae by means of chemical adhesion. Attached micro-organisms secrete extracellular polymeric substances, which we deduce must also provide an additional element of chemical adhesion to mechanically interlocked mesoscopic and macroscopic biomatter. By coupling physical and chemical methods for adhesion, T. cornigera is able to hierarchically decorate its carapace. STATEMENT OF SIGNIFICANCE: Our paper brings to light the unique decorator crab carapace morphology of T. cornigera; and furthermore evidences its function in micro-organism nucleation and adhesion. We show how this special carapace morphology directs and guides water flow to form nesting regions of water stagnation where micro-organisms can nucleate and adhere. In the literature, decorator crab carapaces are presumed to be able to mechanically interlock biomatter as camouflage using hook-like setal outgrowths. T. cornigera contrarily exhibits clusters of hay-stack like structures. By encouraging micro organism adhesion to the carapace setae, T. cornigera is able to effectively attach biomatter using both chemical and physical principles of adhesion. T. cornigera essentially has a super-biofouling carapace surface, for at least micro organisms. Our work will have an impact on researchers interested in biofouling, adhesion, biomedical and purification filter systems, and in the development of novel biomimetic surfaces with tailored properties. PMID- 27184403 TI - A lightweight, biological structure with tailored stiffness: The feather vane. AB - The flying feathers of birds are keratinous appendages designed for maximum performance with a minimum weight penalty. Thus, their design contains ingenious combinations of components that optimize lift, stiffness, aerodynamics, and damage resistance. This design involves two main parts: a central shaft that prescribes stiffness and lateral vanes which allows for the capture of air. Within the feather vane, barbs branch from the shaft and barbules branch from barbs, forming a flat surface which ensures lift. Microhooks at the end of barbules hold barbs tightly together, providing the close-knit, unified structure of the feather vane and enabling a repair of the structure through the reattachment of un-hooked junctions. Both the shaft and barbs are lightweight biological structures constructed of keratin using the common motif of a solid shell and cellular interior. The cellular core increases the resistance to buckling with little added weight. Here we analyze the detailed structure of the feather barb and, for the first time, explain its flexural stiffness in terms of the mechanics of asymmetric foam-filled beams subjected to bending. The results are correlated and validated with finite element modeling. We compare the flexure of single barbs as well as arrays of barbs and find that the interlocking adherence of barbs to one another enables a more robust structure due to minimized barb rotation during deflection. Thus, the flexure behavior of the feather vane can be tailored by the adhesive hooking between barbs, creating a system that mitigates damage. A simplified three-dimensional physical model for this interlocking mechanism is constructed by additive manufacturing. The exceptional architecture of the feather vane will motivate the design of bioinspired structures with tailored and unique properties ranging from adhesives to aerospace materials. STATEMENT OF SIGNIFICANCE: Despite its importance to bird flight, literature characterizing the feather vane is extremely limited. The feather vane is composed of barbs that branch from the main shaft (rachis) and barbules that branch from barbs. In this study, the flexural behavior of the feather barb and the role of barbule connections in reinforcing the feather vane are quantitatively investigated for the first time, both experimentally and theoretically. Through the performed experiments, structure-function relationships within the feather vane are uncovered. Additionally, in the proposed model the sophisticated structure of the barbs and the interlocking mechanism of the feather vane are simplified to understand these processes in order to engineer new lightweight structures and adhesives. PMID- 27184401 TI - Mule Regulates the Intestinal Stem Cell Niche via the Wnt Pathway and Targets EphB3 for Proteasomal and Lysosomal Degradation. AB - The E3 ubiquitin ligase Mule is often overexpressed in human colorectal cancers, but its role in gut tumorigenesis is unknown. Here, we show in vivo that Mule controls murine intestinal stem and progenitor cell proliferation by modulating Wnt signaling via c-Myc. Mule also regulates protein levels of the receptor tyrosine kinase EphB3 by targeting it for proteasomal and lysosomal degradation. In the intestine, EphB/ephrinB interactions position cells along the crypt-villus axis and compartmentalize incipient colorectal tumors. Our study thus unveils an important new avenue by which Mule acts as an intestinal tumor suppressor by regulation of the intestinal stem cell niche. PMID- 27184404 TI - Sulfamethazine-based pH-sensitive hydrogels with potential application for transcatheter arterial chemoembolization therapy. AB - Transcatheter arterial chemoembolization (TACE) is the most common palliative therapy for unresectable hepatocellular carcinoma (HCC). The conventional TACE technique, which employs the Lipiodol(r) emulsion, has been widely used for human cancer treatments. However, this delivery system seems to be inconsistent and unstable in maintaining a high concentration of drugs at tumor sites. An alternative approach for TACE is loading drugs into a liquid embolic solution that exists as an injectable solution and can exhibit a sol-to-gel phase transition to form a solidified state once delivered to the tumor site. Here, we develop a novel sulfamethazine-based anionic pH-sensitive block copolymer with potential application as a radiopaque embolic material. The copolymer, named PCL PEG-SM, and comprised of poly(epsilon-caprolactone), sulfamethazine, and poly(ethylene glycol), was fabricated by free radical polymerization. An aqueous solution of the developed copolymer underwent a sol-to-gel phase transition upon lowering the environmental pH to create a gel region that covered the physiological condition (pH 7.4, 37 degrees C) and the low pH conditions at tumor sites (pH 6.5-7.0, 37 degrees C). The release of doxorubicin (DOX) from DOX loaded copolymer hydrogels could be sustained for more than 4weeks in vitro, and the released DOX retained its fully bioactivity via inhibition the proliferation of hepatic cancer cells. The radiopaque embolic formulations that were prepared by mixing copolymer solutions at pH 8.0 with Lipiodol(r), a long-lasting X-ray contrast agent, could exhibit the gelation inside the tumor after intratumoral injection or intraarterial administration using a VX2 carcinoma hepatic tumor rabbit model. These results suggest that a novel anionic pH-sensitive copolymer has been developed with a potential application as a liquid radiopaque embolic solution for TACE of HCC. STATE OF SIGNIFICANCE: Transcatheter arterial chemoembolization (TACE) has been widely used as a palliative treatment therapy for unresectable hepatocellular carcinoma (HCC). Conventional TACE technique, which usually employs emulsion of DOX-in-Lipiodol(r), followed by an embolic agent, has significant limitation of inconsistency and lack of controlled release ability. To address these limitations of conventional TACE material system, we introduced a novel liquid radiopaque embolic material from our pH-sensitive hydrogel. The material has low viscosity that can be injected via a microcatheter, rather biocompatibility, and drug controlled release ability. Importantly, it can form gel in the tumor as well as tumoral vasculature in response to the lowered pH at the tumor site, which proved the potential for the use to treat HCC by TACE therapy. PMID- 27184405 TI - Iron deficiency anemia's effect on bone formation in zebrafish mutant. AB - Iron is one of the essential elements of life. Iron metabolism is related to bone metabolism. Previous studies have confirmed that iron overload is a risk factor for osteoporosis. But the correlation between iron deficiency and bone metabolism remains unclear. Ferroportin 1 is identified as a cellular iron exporter and required for normal iron cycling. In zebrafish, the mutant of ferroportin 1 gene (fpn1), weh(tp85c) exhibited the defective iron transport, leading to developing severe hypochromic anemia. We used weh(tp85c) as a model for investigating iron deficiency and bone metabolism. In this study, we examined the morphology of the developing cartilage and vertebrae of the Weh(tp85) compared to the wild type siblings by staining the larvae with alcian blue for cartilage and alizarin red for the bone. In addition, we evaluated the expression patterns of the marker genes of bone development and cell signaling in bone formation. Our results showed that weh(tp85c) mutant larvae exhibited the defects in bone formation, revealing by decreases in the number of calcified vertebrae along with decreased expression of osteoblast novel genes: alpl, runx2a and col1a1a and BMPs signaling genes in osteoblast differentiation: bmp2a and bmp2b. Our data suggest that iron deficiency anemia affects bone formation, potentially through the BMPs signaling pathway in zebrafish. PMID- 27184406 TI - Biochemical characterization of human acyl coenzyme A: 2-monoacylglycerol acyltransferase-3 (MGAT3). AB - BACKGROUND: MGAT3 catalyzes the synthesis of 1,2-diacylglycerol from 2 monoacylglycerol in an acyl CoA-dependent reaction. Although initially identified as an MGAT enzyme, MGAT3 is more closely related to DGAT2 than to MGAT1 and MGAT2. Furthermore, MGAT3 possesses both DGAT and MGAT activities, in vitro. MGAT3 is almost exclusively expressed in the small intestine in humans, suggesting that it has a role in dietary fat absorption. Although identified many years ago, little information is available regarding the contribution of MGAT3 to triacylglycerol biosynthesis. RESULTS: This study confirmed the initial observations that MGAT3 possessed both MGAT and DGAT activities. When expressed in cells in culture, MGAT3 stimulated lipid droplet growth, but unlike DGAT2, does not become concentrated around the lipid droplet surface. We also characterized the MGAT activity of an MGAT3 mutant in which a conserved cysteine was changed to a tyrosine residue. Lastly, although they share significant sequence identity, MGAT3 is a much more stable protein than DGAT2, yet they are both polyubiquitinated and degraded through ER-associated degradation by the proteasome. CONCLUSION: Our findings provide additional evidence that MGAT3 likely functions as a TG synthase in cells. PMID- 27184407 TI - Involvement of LSECtin in the hepatic natural killer cell response. AB - Accumulating evidence has indicated that natural killer cells (NK cells) play an important role in immune responses generated in the liver. However, the underlying molecular basis for local immune regulation is poorly understood. Mice were intraperitoneally injected with polyinosinic-polycytidylic acid (PolyI:C) at a dose of 20 mg/kg body wt. The percentage and absolute number of NK cells in the liver were analysed with flow cytometry. LSECtin knockout mice and LSECtin cDNA plasmids were used for analyze the role of LSECtin in hepatic NK cell regulation in vivo. Here, we show that the C-type lectin LSECtin, a member of the DC-SIGN family, is a novel liver regulator for NK cells. LSECtin could bind to NK cells in a carbohydrate-dependent manner and could regulate the number of hepatic NK cells. In the NK cell-mediated acute liver injury model induced with PolyI:C, the exogenous expression of LSECtin accelerated NK cell-induced liver injury, whereas the absence of LSECtin ameliorated this condition. Our results reveal that LSECtin is a novel, liver-specific NK cell regulator that may be a target for the treatment of inflammatory diseases in the liver. PMID- 27184408 TI - Measuring the impact of the working environment on emergency department nurses: A cross-sectional pilot study. AB - BACKGROUND: The emergency department (ED) is characterised by high workload and competing demands. This study describes ED nurses perceptions of their working environment with a sub group analysis for those who also worked at the local police watch house, where individuals are detained in custody. METHODS: A cross sectional pilot study was undertaken involving a survey of nurses working in one ED in Queensland, Australia. The Working Environment Score (WES-10) consists of four subscales: Self Realisation, Workload, Conflict, and Nervousness; and is used to measure stress and staff morale. This was administered at two time periods: T1: May 2013 and T2: July 2013; before and after 10 ED nurses worked in the watch house. RESULTS: Questionnaires were returned by 34 nurses at T1 and 41 nurses at T2. The perception of working environment differed between T1 and T2 for nurse respondents who worked at the local police watch house but not for nurse respondents who did not work in the watch house. Of the four sub-scales, workload was the factor that impacted most on working environment in both groups and was notably higher for those who worked in the watch house and responded at T2. CONCLUSIONS: This pilot study identified that for ED nurses' satisfaction with their working environment was relatively high, although certain areas (e.g., nervousness) were better than others (e.g., workload). The perception of workload was higher for T2 staff offered the opportunity to use their ED skills in a different setting, however further work with a larger sample size is required. PMID- 27184409 TI - Price Discrepancy Between Sellers and Buyers When Making Decisions for the Self and Others. AB - In daily life, people make decisions not only for themselves but also on behalf of others. There may be differences in terms of the endowment effect when making decisions in these two situations. In Study 1, this question was investigated with an existing dataset exploring the traditional endowment effect, in which 86 students (M age = 20.8 years, SD = 5.0) at Harvard University were asked to make a decision on selling or buying a coffee mug for themselves or for others as brokers. When making decisions for the self, the average price demanded by sellers was much higher than that offered by buyers; while making decisions for others, the price discrepancy disappeared. In Study 2, a similar study was conducted with a sample of 42 Chinese university students (M age = 22.3 years, SD = 2.5), and a similar pattern of results was obtained. Further analysis indicated that when making decisions for others, only buyers increased their valuations, therefore mitigating the seller-buyer price discrepancy. Finally, the findings were interpreted from the perspective of Construal Level Theory. PMID- 27184410 TI - Capturing Parent-Child Interactions With Social Media: Comment on Zhang et al. (2015). AB - Zhang et al. conducted a qualitative study of children presented with 19 parental structuring behaviors of parental control and were asked to attribute the parent's intent behind the behaviors. The authors developed several conceptual categories, "parent-centered," "child-centered," or "social" interests. Here, we describe how their 12 propositions could be empirically tested in further studies using social media. PMID- 27184411 TI - School Children's Attributions of Intentions for Parental Behaviors: Development of a Measure. AB - The present study developed a new scale to measure children's attributions of intentions for parental behaviors. The scale has 180 items (18 intentions that children may use to explain why parents perform each of 10 parental behaviors), and was administered to 1973 Chinese students (age range = 9-16 years; M = 12.5, SD = 1.70; 1024 boys and 949 girls). Using half of the sample, 10 exploratory factor analyses were conducted (variance accounted for ranged from 64.24% to 73.32%, M = 69.9%), each on the 18 items associated with one of the 10 parental behaviors. Four factors with eigenvalues over one emerged. The items associated with two of the 10 stimulus behaviors were selected to form a short version. Using the other half of the sample, confirmatory factor analyses on the short version were conducted and provided further support for the four-factor structure. Concurrent validity was assessed by correlations with parental psychological and behavioral control, and gender, age, and grade of the respondents. Test-retest reliability was assessed among 159 of the respondents over a one-month separation. PMID- 27184412 TI - Mortality from neurodegenerative diseases in a cohort of US flight attendants. AB - BACKGROUND: Concern exists about the potential chronic neurological effects among aircrew of exposure to chemical contaminants from engine oil in aircraft cabin air. We evaluated mortality from neurodegenerative diseases among 11,311 former US flight attendants. METHODS: Vital status was ascertained through 2007, and life table analyses were conducted to obtain standardized mortality ratios (SMRs). RESULTS: Amyotrophic lateral sclerosis (ALS) mortality was over twice as high in the cohort as in the US general population, based on nine observed ALS deaths. There was no clear pattern in risk when SMRs for ALS were stratified by exposure duration. Mortality from other neurodegenerative diseases was not elevated. CONCLUSIONS: Our findings are limited due to small numbers of observed deaths and reliance on mortality data, but suggest that flight attendants may have an increased risk of ALS. Additional research is needed. Am. J. Ind. Med. 59:532-537, 2016. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. PMID- 27184413 TI - Behavior of the potential antitumor V(IV)O complexes formed by flavonoid ligands. 3. Antioxidant properties and radical production capability. AB - The radical production capability and the antioxidant properties of some V(IV)O complexes formed by flavonoid ligands were examined. In particular, the bis chelated species of quercetin (que), [VO(que)2](2-), and morin (mor), [VO(mor)2], were evaluated for their capability to reduce the stable radical 1,1-diphenyl-2 picrylhydrazyl (DPPH) and produce the hydroxyl radical (*)OH by Fenton-like reactions, where the reducing agent is V(IV)O(2+). The results were compared with those displayed by other V(IV)O complexes, such as [VO(H2O)5](2+), [VO(acac)2] (acac=acetylacetonate) and [VO(cat)2](2-) (cat=catecholate). The capability of the V(IV)O flavonoids complexes to reduce DPPH is much larger than that of the V(IV)O species formed by non-antioxidant ligands and it is due mainly to the flavonoid molecule. Through the 5,5-dimethyl-1-pyrroline N-oxide (DMPO) spin trapping assay of the hydroxyl radical it was possible to demonstrate that in acidic solution V(IV)O(2+) has an effectiveness in producing (*)OH radicals comparable to that of Fe(2+). When V(IV)O complexes of flavonoids were taken into account, the amount of hydroxyl radicals produced in Fenton-like reactions depends on the specific structure of the ligand and on their capability to reduce H2O2 to give (*)OH. Both the formation of reactive oxygen species (ROS) under physiological conditions by V(IV)O complexes of flavonoid ligands and their radical scavenging capability can be put in relationship with their antitumor effectiveness and it could be possible to modulate these actions by changing the features of the flavonoid coordinated to the V(IV)O(2+) ion, such as the entity, nature and position of the substituents and the number of phenolic groups. PMID- 27184414 TI - Concurrent alcohol and medication poisoning hospital admissions among older rural and urban residents. AB - BACKGROUND: Alcohol and medication interactions are projected to increase due to the growth of older adults that are unsafely consuming alcohol and medications. Plus, aging adults who reside in rural areas are at the highest risk of experiencing medication interactions. OBJECTIVE: Estimate concurrent alcohol and medication (alcohol/medication) hospitalizations in adults 50+ years, comparing age groups and rural/urban regions. METHODS: Kentucky nonfederal, acute care inpatient hospital discharge electronic records for individuals aged 50+ years from 2001 to 2012 were examined. Rate differences were estimated across age and regional strata. Differences in the underlying principal diagnosis, intent, and medications were also examined. RESULTS: There were 2168 concurrent alcohol/medication hospitalizations among 50+ year olds identified. There was a 187% increase in alcohol/medication hospitalizations from 2001 (n = 104) to 2012 (n = 299). The per capita alcohol/medication hospitalization rate increased from 8.91 (per 100,000) in 2001 to 19.98 (per 100,000) in 2012, a 124% increase. The characteristics of the hospitalizations included 75% principal diagnosis as medication poisoning, self-harm as the primary intent (55%) in 50-64-year olds, and unintentional intent (41%) in 65+ adults. Benzodiazepines were most often involved in the poisonings (36.5%). CONCLUSIONS: Concurrent alcohol/medication hospitalizations in Kentucky are increasing among aging adults. Greater increases in rural areas and the 65+ aged adults were seen, although there were also higher alcohol/medication hospitalizations in urban and 50-64 aged adults. These findings indicate the need for public-health prevention and clinical intervention to better educate and manage alcohol consuming older adults on safe medication and alcohol practices. PMID- 27184416 TI - Gain-scheduling multivariable LPV control of an irrigation canal system. AB - The purpose of this paper is to present a multivariable linear parameter varying (LPV) controller with a gain scheduling Smith Predictor (SP) scheme applicable to open-flow canal systems. This LPV controller based on SP is designed taking into account the uncertainty in the estimation of delay and the variation of plant parameters according to the operating point. This new methodology can be applied to a class of delay systems that can be represented by a set of models that can be factorized into a rational multivariable model in series with left/right diagonal (multiple) delays, such as, the case of irrigation canals. A multiple pool canal system is used to test and validate the proposed control approach. PMID- 27184415 TI - Inhibiting complex IL-17A and IL-17RA interactions with a linear peptide. AB - IL-17A is a pro-inflammatory cytokine that has been implicated in autoimmune and inflammatory diseases. Monoclonal antibodies inhibiting IL-17A signaling have demonstrated remarkable efficacy, but an oral therapy is still lacking. A high affinity IL-17A peptide antagonist (HAP) of 15 residues was identified through phage-display screening followed by saturation mutagenesis optimization and amino acid substitutions. HAP binds specifically to IL-17A and inhibits the interaction of the cytokine with its receptor, IL-17RA. Tested in primary human cells, HAP blocked the production of multiple inflammatory cytokines. Crystal structure studies revealed that two HAP molecules bind to one IL-17A dimer symmetrically. The N-terminal portions of HAP form a beta-strand that inserts between two IL-17A monomers while the C-terminal section forms an alpha helix that directly blocks IL-17RA from binding to the same region of IL-17A. This mode of inhibition suggests opportunities for developing peptide antagonists against this challenging target. PMID- 27184419 TI - Quorum Signal Inhibitors and Their Potential Use against Fish Diseases. AB - Quorum sensing (QS) is a process of bacterial communication used to control group behaviors, including bioluminescence, virulence factor production, biofilm formation, and biofilm antimicrobial tolerance. Many aquatic bacterial pathogens such as Aeromonas, Vibrio, and Edwardsiella spp. use QS to regulate virulence factor production. The disruption of QS has been shown to be an effective strategy in the competition between higher organisms and bacteria and more recently between bacterial species. For this reason, QS disruption has been proposed as a strategy to prevent bacterial pathogenicity. In this review, we summarize the current literature and illustrate the value of QS inhibitors in controlling virulence production in aquatic bacterial pathogens. This represents a new, nonantibiotic strategy to combat fish diseases. Received August 11, 2015; accepted January 26, 2016. PMID- 27184420 TI - Excretion of infectious Zika virus in urine. PMID- 27184421 TI - Zika virus and GLUT1. PMID- 27184422 TI - Electrochemical deposition of highly-conducting metal dithiolene films. AB - Electrochemical deposition has been used to prepare a thin film of neutral 4',4 (3-alkyl)-thiophene-5',5-hydogen-nickel and copper dithiolenes (Ni-C2, Cu-C2). The application of molecular electrodeposition provides a means to solution process molecular semiconductors of poor solubility, which results from the strong intermolecular interaction required for charge transport. Both Ni-C2 and Cu-C2 form continuous thin films that show intense NIR absorptions, extending to 1800 nm and 2000 nm respectively giving evidence for the strong intermolecular interactions in the solid state. Both films are highly conducting and temperature dependence of resistance gave an activation energy of 0.42 eV and 0.072 eV respectively, with the near-metallic behaviour of Cu-C2 attributed to the additional presence of an unpaired electron. PMID- 27184418 TI - Pharmacokinetics of metronomic chemotherapy: a neglected but crucial aspect. AB - Metronomic chemotherapy describes the close, regular administration of chemotherapy drugs at less-toxic doses over prolonged periods of time. In 2015, the results of randomized phase III clinical trials demonstrated encouraging, albeit limited, efficacy benefits of metronomic chemotherapy regimens administered as adjuvant maintenance therapy for the treatment of breast cancer, or as maintenance therapy in combination with an antiangiogenic agent for metastatic colorectal cancer. Owing to the investigational nature of this approach, metronomic chemotherapy regimens are highly empirical in terms of the optimal dose and schedule for the drugs administered; therefore, greater knowledge of the pharmacokinetics of metronomic chemotherapy is critical to the future success of this treatment strategy. Unfortunately, such preclinical and clinical pharmacokinetic studies are rare. Herein, we present situations in which active drug concentrations have been achieved with metronomic schedules, and discuss their associated pharmacokinetic parameters. We summarize examples from the limited number of clinical studies in order to illustrate the importance of assessing such pharmacokinetic parameters, and discuss the influence this information can have on improving efficacy and reducing toxicity. PMID- 27184423 TI - Improving productive performance and mitigating harmful emissions from laying hen excreta via feeding on graded levels of corn DDGS with or without Bacillus subtilis probiotic. AB - An experiment that included some inclusions of corn distillers dried grains with solubles (DDGS) with or without supplementation of probiotic bacteria to Hi-sex Brown laying hen diets was conducted to evaluate the impacts on performance, egg quality, blood metabolites and nitrogen and phosphorus excretion in the manure. A total of 216 twenty-two-week-old Hi-sex Brown laying hens were randomly divided into eight treatment groups in a factorial design (4 * 2) experiment, which included four levels of DDGS (0, 50, 100 and 150 g/kg diet) plus two levels of Bacillus subtilis probiotic (0 or 1000 mg/kg diet, with a concentration of 1.5 * 108 CFU/g of dried product). The experimental period extended from 22 to 34 weeks of age. The results showed that linear increase in DDGS level up to 150 g/kg improved (p <= 0.01) the values of feed consumption, egg shape index and yolk colour compared to the control and other treatment groups. Inclusion of dietary DDGS up to 150 g/kg in layer diets led to a significant decrease in egg mass and a significant increase in Haugh unit score compared to other groups. In the bacillus group, the values of feed conversion, egg weight and egg mass enhanced by 6.45, 3.27 and 7.60% respectively compared with the control diet. Total protein, albumin, triglycerides, cholesterol, calcium and ammonia in serum were significantly (p <= 0.01) influenced by DDGS inclusion. The excreted nitrogen decreased by 8.62 and 4.31% in hens fed 50 or 100 g/kg of DDGS respectively, while excreted phosphorous decreased by 3.33, 7.22 and 10.56% in hens fed 50, 100 or 150 g/kg of DDGS respectively as compared to the control group. It could be concluded that increasing DDGS inclusion level in the diet up to 10% and the supplementation of probiotic bacteria improved the productive performance of laying hens and mitigated the harmful emissions from chicken manure; this means better production within environmentally friendly conditions. PMID- 27184417 TI - Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease. AB - Chemotherapy is the primary established systemic treatment for patients with triple-negative breast cancer (TNBC) in both the early and advanced-stages of the disease. The lack of targeted therapies and the poor prognosis of patients with TNBC have fostered a major effort to discover actionable molecular targets to treat patients with these tumours. Massively parallel sequencing and other 'omics' technologies have revealed an unexpected level of heterogeneity of TNBCs and have led to the identification of potentially actionable molecular features in some TNBCs, such as germline BRCA1/2 mutations or 'BRCAness', the presence of the androgen receptor, and several rare genomic alterations. Whether these alterations are molecular 'drivers', however, has not been clearly established. A subgroup of TNBCs shows a high degree of tumour-infiltrating lymphocytes that also correlates with a lower risk of disease relapse and a higher likelihood of benefit from chemotherapy. Proof-of-principle studies with immune-checkpoint inhibitors in advanced-stage TNBC have yielded promising results, indicating the potential benefit of immunotherapy for patients with TNBC. In this Review, we discuss the most relevant molecular findings in TNBC from the past decade and the most promising therapeutic opportunities derived from these data. PMID- 27184425 TI - Updates in preserving reproductive potential of prepubertal girls with cancer: Systematic review. AB - INTRODUCTION: With increasing numbers of adult female survivors of childhood cancers due to advances in early diagnosis and treatment, the issue of preserving the reproductive potential of prepubertal girls undergoing gonadotoxic treatments has gained greater attention. METHODS: According to PRISMA guidelines, a systematic review of the literature was performed for all relevant full-text articles published in PubMed in English throughout the past 15 years to explore the significant updates in preserving the reproductive potential of prepubertal girls with cancer. RESULTS: The two established fertility preservation options, embryo freezing and egg freezing, cannot be offered routinely to prepubertal girls as these options necessitate prior ovarian stimulation and subsequent mature oocytes retrieval that are contraindicated or infeasible before puberty. Therefore, the most suitable fertility preservation options to prepubertal girls are (1) ovarian tissue freezing and autotransplantation, (2) in vitro maturation, and (3) ovarian protection techniques. In this review, we discuss in detail those options as well as their success rates, advantages, disadvantages and future directions. We also suggest a new integrated strategy to preserve the reproductive potential of prepubertal girls with cancer. CONCLUSION: Although experimental, ovarian tissue slow freezing and orthotopic autotransplantation may be the most feasible option to preserve the reproductive potential of prepubertal girls with cancer. However, this technique has two major and serious disadvantages: (1) the risk of reintroducing malignant cells, and (2) the relatively short lifespan of ovarian tissue transplants. Several medical and ethical considerations should be taken into account before applying this technique to prepubertal girls with cancer. PMID- 27184424 TI - KLF4 transcriptionally activates non-canonical WNT5A to control epithelial stratification. AB - Epithelial differentiation and stratification are essential for normal homeostasis, and disruption of these processes leads to both injury and cancer. The zinc-finger transciption factor KLF4 is a key driver of epithelial differentiation, yet the mechanisms and targets by which KLF4 controls differentiation are not well understood. Here, we define WNT5A, a non-canonical Wnt ligand implicated in epithelial differentiation, repair, and cancer, as a direct transcriptional target that is activated by KLF4 in squamous epithelial cells. Further, we demonstrate functionally that WNT5A mediates KLF4 control of epithelial differentiation and stratification, as treatment of keratinocytes with WNT5A rescues defective epithelial stratification resulting from KLF4 loss. Finally, we show that the small GTPase CDC42 is regulated by KLF4 in a WNT5A dependent manner. As such, we delineate a novel pathway for epithelial differentiation and stratification and define potential therapeutic targets for epithelial diseases. PMID- 27184427 TI - Effect of cassava pulp supplement on 1,3-propanediol production by Clostridium butyricum. AB - To improve its 1,3-propanediol (1,3-PD) production, Clostridium butyricum was cultivated on glycerol medium supplemented with cassava pulp (CP). At small concentrations, the CP improved the 1,3-PD productivity of C. butyricum from (0.25+/-0.01)g/L/h (glycerol alone) to (0.43+/-0.02)g/L/h (glycerol+2g/L CP) after 24h fermentation. PMID- 27184428 TI - Engineering of Corynebacterium glutamicum for xylitol production from lignocellulosic pentose sugars. AB - Xylitol is a non-fermentable sugar alcohol used as sweetener. Corynebacterium glutamicum ATCC13032 was metabolically engineered for xylitol production from the lignocellulosic pentose sugars xylose and arabinose. Direct conversion of xylose to xylitol was achieved through the heterologous expression of NAD(P)H-dependent xylose reductase (xr) gene from Rhodotorula mucilaginosa. Xylitol synthesis from arabinose was attained through polycistronic expression of l-arabinose isomerase (araA), d-psicose 3 epimerase (dpe) and l-xylulose reductase (lxr) genes from Escherichia coli, Agrobacterium tumefaciens and Mycobacterium smegmatis, respectively. Expression of xr and the synthetic araA-dpe-lxr operon under the control of IPTG-inducible Ptac promoter enabled production of xylitol from both xylose and arabinose in the mineral (CGXII) medium with glucose as carbon source. Additional expression of a pentose transporter (araTF) gene enhanced xylitol production by about four-fold compared to the parent strain. The constructed strain Cg-ax3 produced 6.7+/-0.4g/L of xylitol in batch fermentations and 31+/ 0.5g/L of xylitol in fed-batch fermentations with a specific productivity of 0.28+/-0.05g/g cdw/h. The strain Cg-ax3 was also validated for xylitol production from pentose rich, acid pre-treated liquor of sorghum stover (SAPL) and the results were comparable in both SAPL (27+/-0.3g/L) and mineral medium (31+/ 0.5g/L). PMID- 27184426 TI - GM-CSF Mediates Mesenchymal-Epithelial Cross-talk in Pancreatic Cancer. AB - Pancreatic ductal adenocarcinoma (PDA) is characterized by a dense stroma consisting of a prevalence of activated fibroblasts whose functional contributions to pancreatic tumorigenesis remain incompletely understood. In this study, we provide the first identification and characterization of mesenchymal stem cells (MSC) within the human PDA microenvironment, highlighting the heterogeneity of the fibroblast population. Primary patient PDA samples and low passage human pancreatic cancer-associated fibroblast cultures were found to contain a unique population of cancer-associated MSCs (CA-MSC). CA-MSCs markedly enhanced the growth, invasion, and metastatic potential of PDA cancer cells. CA MSCs secreted the cytokine GM-CSF that was required for tumor cell proliferation, invasion, and transendothelial migration. Depletion of GM-CSF in CA-MSCs inhibited the ability of these cells to promote tumor cell growth and metastasis. Together, these data identify a population of MSCs within the tumor microenvironment that possesses a unique ability, through GM-CSF signaling, to promote PDA survival and metastasis. SIGNIFICANCE: The role of stroma in pancreatic cancer is controversial. Here, we provide the first characterization of MSCs within the human PDA microenvironment and demonstrate that CA-MSCs promote tumorigenesis through the production of GM-CSF. These data identify a novel cytokine pathway that mediates mesenchymal-epithelial cross-talk and is amenable to therapeutic intervention. Cancer Discov; 6(8); 886-99. (c)2016 AACR.This article is highlighted in the In This Issue feature, p. 803. PMID- 27184429 TI - Cocoa pod husk: A new source of CLEA-lipase for preparation of low-cost biodiesel: An optimized process. AB - Enzymatic reactions involving lipases as catalyst in transesterification can be an excellent alternative to produce environmental-friendly biodiesel. In this study, lipase extracted from Cocoa Pod Husk (CPH) and immobilized through cross linked enzyme aggregate (CLEA) technology catalysed the transesterification of Jatropha curcas oil successfully. Face centered central composite design (FCCCD) under response surface methodology (RSM) was used to get the optimal conditions of 3% (w/w) enzyme loading, 4h reaction time and 1:6 oil/ethanol ratio to achieve the highest conversion of free fatty acid and glycerides into biodiesel (93%). The reusability of CLEA-lipase was tested and after seven cycles, the conversion percentage reduced to 58%. The results revealed that CLEA lipase from CPH is a potential catalyst for biodiesel production. PMID- 27184430 TI - Production of omega-hydroxy octanoic acid with Escherichia coli. AB - The present proof-of-concept study reports the construction of a whole-cell biocatalyst for the de novo production of omega-hydroxy octanoic acid. This was achieved by hijacking the natural fatty acid cycle and subsequent hydroxylation using a specific monooxygenase without the need for the additional feed of alkene like precursors. For this, we used the model organism Escherichia coli and increased primarily the release of the octanoic acid precursors by overexpressing the plant thioesterase FatB2 from Cuphea hookeriana in a beta-oxidation deficient strain, which lead to the production of 2.32mM (8.38mggcww(-1)) octanoic acid in 24h. In order to produce the corresponding omega-hydroxy derivative, we additionally expressed the engineered self-sufficient monooxygenase fusion protein CYP153AMaq(G307A)-CPRBM3 within the octanoic acid producing strain. With this, we finally produced 234MUM (0.95mggcww(-1)) omega-hydroxy octanoic acid in a 20h fed-batch set-up. PMID- 27184431 TI - Complete genome sequence of the crude oil-degrading thermophilic bacterium Geobacillus sp. JS12. AB - Here, we report the complete genome sequence of Geobacillus sp. JS12, isolated from composts located in Namhae, Korea, which shows extracellular lipolytic activities at high temperatures. An array of genes related to the utilization of lipids was identified by whole genome analysis. The genome sequence of the strain JS12 provides basic information for wider exploitation of thermostable industrial lipases. PMID- 27184432 TI - Complete genome sequence of Bacillus subtilis BSD-2, a microbial germicide isolated from cultivated cotton. AB - Bacillus subtilis BSD-2, isolated from cotton (Gossypium spp.), had strong antagonistic activity to Verticillium dahlia Kleb and Botrytis cinerea. We sequenced and annotated the BSD-2 complete genome to help us the better use of this strain, which has surfactin, bacilysin, bacillibactin, subtilosin A, Tas A and a potential class IV lanthipeptide biosynthetic pathways. PMID- 27184433 TI - Chromatin and epigenetics in all their states: Meeting report of the first conference on Epigenetic and Chromatin Regulation of Plant Traits - January 14 - 15, 2016 - Strasbourg, France. AB - In January 2016, the first Epigenetic and Chromatin Regulation of Plant Traits conference was held in Strasbourg, France. An all-star lineup of speakers, a packed audience of 130 participants from over 20 countries, and a friendly scientific atmosphere contributed to make this conference a meeting to remember. In this article we summarize some of the new insights into chromatin, epigenetics, and epigenomics research and highlight nascent ideas and emerging concepts in this exciting area of research. PMID- 27184435 TI - Psychiatric and Behavioural Disorders in Children with Epilepsy (ILAE Task Force Report): Anxiety, depression and childhood epilepsy. AB - Anxiety and depression are relatively common in children with epilepsy: anxiety has been reported in 15-36% and depression in 8-35% of patients. In some cases these conditions may be related specifically to the epilepsy or its treatment. For example, some antiepileptic drugs are known to be associated with depression in adults and are likely to have a similar effect in young people. Emotional reactions to the epilepsy, for example anxieties and social phobia related specifically to the seizures, might be expected and require appropriate management. However, there is a growing recognition of the bidirectional relationship between epilepsy and psychiatric disorders, including depression, largely based on adult data. Cognitive behavioural therapy and serotonin reuptake inhibitors are used for treatment of both anxiety and depression in children with epilepsy. There is a need for greater understanding of the causes of these conditions in young people and there is also a need for better evidence for optimal treatment. PMID- 27184436 TI - In vitro evaluation of 2-hydroxyalkylated beta-cyclodextrins as potential therapeutic agents for Niemann-Pick Type C disease. AB - This study was conducted to evaluate the attenuating potential of 2-hydroxypropyl beta-cyclodextrin (HPBCD) against Niemann-Pick Type C (NPC) disease, as well as the physical and chemical properties, particularly the cholesterol-solubilizing ability, in an NPC disease model in vitro. As parameters of NPC abnormalities, intracellular free and esterified cholesterol levels and lysosome volume were measured in Npc1 null Chinese hamster ovary cells. HPBCD showed dose-dependent effects against dysfunctional intracellular cholesterol trafficking, such as the accumulation and shortage of free and esterified cholesterols, respectively, in Npc1 null cells. However, the effectiveness was gradually offset by exposure to >=8mM HPBCD. The same effect was also observed for increasing lysosome volume in Npc1 null cells. The degree of substitution of the hydroxypropyl group had little influence on the attenuating effects of HPBCD against the NPC abnormalities, at least in the range between 2.8 and 7.4. Next, we compared the effects of other hydroxyalkylated beta-cyclodextrin derivatives with different cholesterol solubilizing abilities, such as 2-hydroxyethyl-beta-cyclodextrin (HEBCD) and 2 hydroxybutyl-beta-cyclodextrin (HBBCD). The cholesterol solubilizing potential, attenuating effects against NPC abnormalities and cytotoxicity induction were HBBCD?HPBCD>HEBCD, HBBCD=HPBCD>HEBCD and HBBCD?HPBCD=HEBCD, respectively. HPBCD may be superior in terms of safety and efficacy in Npc1 null cells compared with HEBCD and HBBCD. The results of this study will provide a rationale for the optimization of HPBCD therapy for NPC disease. PMID- 27184434 TI - Flavonoid and lignan intake and pancreatic cancer risk in the European prospective investigation into cancer and nutrition cohort. AB - Despite the potential cancer preventive effects of flavonoids and lignans, their ability to reduce pancreatic cancer risk has not been demonstrated in epidemiological studies. Our aim was to examine the association between dietary intakes of flavonoids and lignans and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 865 exocrine pancreatic cancer cases occurred after 11.3 years of follow-up of 477,309 cohort members. Dietary flavonoid and lignan intake was estimated through validated dietary questionnaires and the US Department of Agriculture (USDA) and Phenol Explorer databases. Hazard ratios (HR) and 95% confidence intervals (CIs) were calculated using age, sex and center-stratified Cox proportional hazards models, adjusted for energy intake, body mass index (BMI), smoking, alcohol and diabetes status. Our results showed that neither overall dietary intake of flavonoids nor of lignans were associated with pancreatic cancer risk (multivariable-adjusted HR for a doubling of intake = 1.03, 95% CI: 0.95-1.11 and 1.02; 95% CI: 0.89-1.17, respectively). Statistically significant associations were also not observed by flavonoid subclasses. An inverse association between intake of flavanones and pancreatic cancer risk was apparent, without reaching statistical significance, in microscopically confirmed cases (HR for a doubling of intake = 0.96, 95% CI: 0.91-1.00). In conclusion, we did not observe an association between intake of flavonoids, flavonoid subclasses or lignans and pancreatic cancer risk in the EPIC cohort. PMID- 27184437 TI - Effects of prenatal exposure to antipsychotic risperidone on developmental neurotoxicity, apoptotic neurodegeneration and neurobehavioral sequelae in rat offspring. AB - A tremendous increase has been documented in the recent past in prescribing second generation atypical antipsychotic drugs (AAPDs) to the pregnant women with psychosis, considering their reproductive and teratogenic safety. Among AAPDs, risperidone (RIS) ranked third after olanzapine (OLZ) and quetiapine (QUE) used during pregnancy, as OLZ is associated to substantial weight gain in adults and offspring. Although teratogenic safety of RIS has been established, its potential role in developmental neurotoxicity and related neurobehavioral impairments in adolescents has not been documented so far. Therefore, present study has been undertaken to elucidate the effect of prenatal exposure to risperidone (RIS) on developmental neurotoxicity and apoptotic neurodegeneration in neocortical region of fetal brain; and related functional sequelae in young rat offspring. The pregnant Wistar rats were exposed to RIS at 0.8, 1.0 and 2.0mg/kg, at equivalent therapeutic doses, orally from GD 6 to 21. Half of the pregnant rats were sacrificed and their brains were collected, weighed, and processed for neurohistopathological and apoptotic neurodegenerative evaluation. The remaining dams were allowed to deliver naturally, and their offspring were reared up to 10 weeks for neurobehavioral study. Prenatal exposure to RIS induced significant stunting of fetal body and brain weight, substantial reduction in the thickness of neocortical layers and apoptotic neurodegeneration in fetal brains, and delayed postnatal development and growth of the offspring; as well as long- lasting impact on anxiety like impaired behavioral responses on explorative mazes. Therefore, health care providers should be careful in prescribing atypical antipsychotics in general and RIS in particular, to the pregnant psychotic population. PMID- 27184439 TI - Progressive dysarthria and augmentative and alternative communication in conversation: establishing the reliability of the Dysarthria-in-Interaction Profile. AB - BACKGROUND: The Dysarthria-in-Interaction Profile's potential contribution to the clinical assessment of dysarthria-in-conversation has been outlined in the literature, but its consistency of use across different users has yet to be reported. AIMS: To establish the level of consistency across raters on four different interaction categories. That is, how reliable clinicians are when rating a series of videos. A secondary aim was to investigate the relationship between raters' estimates of dysarthric speech intelligibility and their rating of each dyad's overall interaction. METHODS & PROCEDURES: Ten UK speech and language therapists rated independently a series of 40 video samples featuring people with progressive dysarthria in conversation with family members. An equal number of video samples was selected from a collection of recordings featuring four different types of interactional relationship. OUTCOMES & RESULTS: The results show that practising speech and language therapists can rate consistently, and with a high degree of agreement, a series of everyday conversation videos featuring dyads with progressive dysarthria and presenting at different interaction levels. The results also indicate that speech intelligibility does not predict the level of impairment in the interaction in a systematic way suggesting that conversation contains elements that are not directly related to speech intelligibility. CONCLUSIONS & IMPLICATIONS: Further work is required to establish the clinical functionality of this tool, but the results presented here support the development of this conversation profiling system, particularly for people experiencing significant intelligibility problems but remaining highly interactive/communicative. PMID- 27184438 TI - Neonatal anoxia leads to time dependent progression of mitochondrial linked apoptosis in rat cortex and associated long term sensorimotor deficits. AB - Neonatal anoxia arises due to oxygen deprivation at the time of birth and results in life long neurodevelopmental deficits and sometimes may lead to death. The present study investigated the time dependent cortical mitochondrial dysfunction linked apoptosis and related sensorimotor deficits in neonates. Neonates after 30h to birth (P2) were subjected to anoxia of two episodes (10min in each) at a time interval of 24h by passing 100% N2 into an enclosed chamber as confirmed by pulse oximetry. Sensorimotor activities like reflex latency and hanging latency were carried out 24h after last anoxic episode i.e. from P4 (day-1) and continued up to P10 (day-7). Mitochondrial dysfunction after anoxia was evident by the decrease in respiration states, respiratory control ratio (RCR), antioxidant enzyme activity but an increase in oxidative stress and lipid peroxidation and alteration in mitochondrial membrane potential (MMP) at different time points (30min, 24h and day-7). A change in expression of Bcl-2 family proteins and opening of mitochondrial transition pore (mPTP) in terms of mitochondrial swelling was observed resulting in release of cytochrome-C which further activated intrinsic (mitochondrial) pathway of apoptosis through increased expression of caspase-9/3 as confirmed by flow cytometry. In conclusion, anoxia injury leads to progressive activation of mitochondrial events leading to increase in apoptotic cell death following secondary pathological insult. Therefore, strategies in limiting mitochondrial-linked apoptosis during the secondary insult input process may be useful in treatment of long term sensorimotor deficits following anoxia. PMID- 27184440 TI - New lipid-dependent Malassezia species from parrots. AB - BACKGROUND: All the currently recognized Malassezia species have been isolated from mammals. However, only a few of them have been isolated from birds. In fact, birds have been less frequently studied as carriers of Malassezia yeasts than mammals. AIM: In this study we describe two new taxa, Malassezia brasiliensis sp. nov. and Malassezia psittaci sp. nov. METHODS: The isolates studied in this publication were isolated from pet parrots from Brazil. They were characterized using the current morphological and physiological identification scheme. DNA sequencing and analysis of the D1/D2 regions of the 26S rRNA gene, the ITS-5.8S rRNA gene sequences and the beta-tubulin gene were also performed. RESULTS: The strains proposed as new species did not completely fit the phenotypic profiles of any the described species. The validation of these new species was supported by analysis of the genes studied. The multilocus sequence analysis of the three loci provides robust support to delineate these species. CONCLUSIONS: These studies confirm the separation of these two new species from the other species of the genus Malassezia, as well as the presence of lipid-dependent Malassezia yeasts on parrots. PMID- 27184442 TI - Versatile theranostics agents designed by coating ferrite nanoparticles with biocompatible polymers. AB - Three biocompatible polymers, polyethylene glycol (PEG), dextran and chitosan, have been used in this work to control the colloidal stability of magnetic nanoparticles (14 +/- 5 nm in diameter) and to vary the aggregation state in order to study their effect on relaxometric and heating properties. Two different coating strategies have been deeply developed; one based on the formation of an amide bond between citric acid coated nanoparticles (NPs) and amine groups present on the polymer surface and the other based on the NP encapsulation. Relaxometric properties revealed that proton relaxation rates strongly depend on the coating layer hydrophilicity and the aggregation state of the particles due to the presence of magnetic interactions. Thus, while PEG coating reduces particle aggregation by increasing inter-particle spacing leading to reduction of both T1 and T2 relaxation, dextran and chitosan lead to an increase mainly in T2 values due to the aggregation of particles in bigger clusters where they are in close contact. Dextran and chitosan coated NPs have also shown a remarkable heating effect during the application of an alternating magnetic field. They have proved to be potential candidates as theranostic agents for cancer diagnosis and treatment. Finally, cytotoxicity of PEG conjugated NPs, which seem to be ideal for intravenous administration because of their small hydrodynamic size, was investigated resulting in high cell viability even at 0.2 mg Fe ml(-1) after 24 h of incubation. This suspension can be used as drug/biomolecule carrier for in vivo applications. PMID- 27184441 TI - Massive obstetric hemorrhage: Current approach to management. AB - Massive obstetric hemorrhage is a major cause of maternal mortality and morbidity worldwide. It is defined (among others) as the loss of>2,500ml of blood, and is associated to a need for admission to critical care and/or hysterectomy. The relative hemodilution and high cardiac output found in normal pregnancy allows substantial bleeding before a drop in hemoglobin and/or hematocrit can be identified. Some comorbidities associated with pregnancy can contribute to the occurrence of catastrophic bleeding with consumption coagulopathy, which makes the situation even worse. Optimization, preparation, rational use of resources and protocolization of actions are often useful to improve outcomes in patients with postpartum hemorrhage. Using massive obstetric hemorrhage protocols is useful for facilitating rapid transfusion if needed, and can also be cost effective. If hypofibrinogenemia during the bleeding episode is identified, early fibrinogen administration can be very useful. Other coagulation factors in addition to fibrinogen may be necessary during postpartum hemorrhage replacement measures in order to effectively correct coagulopathy. A hysterectomy is recommended if the medical and surgical measures prove ineffective. PMID- 27184443 TI - Harnessing Buckling to Design Architected Materials that Exhibit Effective Negative Swelling. AB - Inspired by the need to develop materials capable of targeted and extreme volume changes during operation, numerical simulations and experiments are combined to design a new class of soft architected materials that achieve a reduction of projected surface-area coverage during swelling. PMID- 27184444 TI - Response to Letter to the Editor "A Quality Improvement Project to Improve and Reduce the Use of Hand Mitt Restraints in Nursing Home Residents". PMID- 27184445 TI - Cardiotoxicity screening with simultaneous optogenetic pacing, voltage imaging and calcium imaging. AB - INTRODUCTION: The Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative seeks an in vitro test to accurately predict clinical Torsades de Pointes (TdP). We developed a cardiotoxicity assay incorporating simultaneous measurement of the action potential (AP) waveform and Ca(2+) transient (CT) in human iPSC-derived cardiomyocytes (CMs). Concurrent optogenetic pacing provided a well-controlled electrophysiological background. METHODS: We used the Optopatch platform for all optical electrophysiology (Hochbaum et al., 2014). In a monolayer culture, a subset of cells expressed a genetically encoded, calcium and voltage reporter, CaViar (Hou, Kralj, Douglass, Engert, & Cohen, 2014), while others expressed a channelrhodopsin variant, CheRiff. Optical pacing of CheRiff-expressing cells synchronized the syncytium. We screened 12 compounds (11 acute, 1 chronic) to identify electrophysiological (AP rise time, AP50, AP90, beat rate) and CT effects in spontaneously beating and paced cultures (1Hz, 2Hz). RESULTS: CaViar reported spontaneous and paced APs and CTs with high signal-to-noise ratio and low phototoxicity. Quinidine, flecainide, E-4031, digoxin and cisapride prolonged APs, while verapamil and nifedipine shortened APs. Early after depolarizations (EADs) were elicited by quinidine, flecainide and cisapride. All but four compounds (amiodarone, chromanol, nifedipine, verapamil) prolonged AP rise time. Nifedipine and verapamil decreased CT amplitude, while digoxin increased CT amplitude. Pentamidine prolonged APs after chronic exposure. DISCUSSION: The Optopatch platform provides a robust assay to measure APs and CTs in hiPSC-CMs. This addresses the CiPA mandate and will facilitate comparisons of cell-based assays to human clinical data. PMID- 27184446 TI - Biochar as a novel niche for culturing microbial communities in composting. AB - Biochar has been applied as a bulk agent or an additive to compost. The mixture of biochar and compost has been considered to exert synergistic effect as a soil amendment. In a composting system, the macro-porous sites of biochar may act as a novel niche that selects and cultures the microorganisms from the bulk compost. A variety of volatile organic carbons (VOCs) such as aromatic hydrocarbons and aliphatics were detected in biochar pellets (BC) pyrolyzed at 100 degrees C. In the mesosphilic phase, the water-soluble carbon (WSC) and water-soluble phenols (WSP) in biochar increased from 2.1 to 26mgkg(-1) and 5.9 to 101MUgkg(-1), respectively. These labile carbons however, were subjected to a rapid metabolism over the composting course. We further compared the responses of microbial community in BC to those in the bulk organic matter. Both Shannon-Wiener and Richness indexes of bacterial communities were higher in BC than in the adjacent compost (ADJ) and the bulk organic matter (control). As for fungal communities, the two indexes were higher in BC than ADJ and control only in the mature phase. During the composting course, the bacterial activity was higher than the fungal counterpart in terms of the changes of corresponding biomarkers, glucosamine and muramic acids. The results suggested that the diversified labile carbons sources including VOCs and WSC in BC could influence the structure of microbial community and resulted in an enhanced carbon catabolic capacity. PMID- 27184447 TI - Utilization of agricultural and forest industry waste and residues in natural fiber-polymer composites: A review. AB - Natural fiber-polymer composites (NFPCs) are becoming increasingly utilized in a wide variety of applications because they represent an ecological and inexpensive alternative to conventional petroleum-derived materials. On the other hand, considerable amounts of organic waste and residues from the industrial and agricultural processes are still underutilized as low-value energy sources. Organic materials are commonly disposed of or subjected to the traditional waste management methods, such as landfilling, composting or anaerobic digestion. The use of organic waste and residue materials in NFPCs represents an ecologically friendly and a substantially higher value alternative. This is a comprehensive review examining how organic waste and residues could be utilized in the future as reinforcements or additives for NFPCs from the perspective of the recently reported work in this field. PMID- 27184448 TI - Thermal and catalytic pyrolysis of a mixture of plastics from small waste electrical and electronic equipment (WEEE). AB - Pyrolysis seems a promising route for recycling of heterogeneous, contaminated and additives containing plastics from waste electrical and electronic equipment (WEEE). This study deals with the thermal and catalytic pyrolysis of a synthetic mixture containing real waste plastics, representative of polymers contained in small WEEE. Two zeolite-based catalysts were used at 400 degrees C: HUSY and HZSM 5 with a high silica content, while three different temperatures were adopted for the thermal cracking: 400, 600 and 800 degrees C. The mass balance showed that the oil produced by pyrolysis is always the main product regardless the process conditions selected, with yields ranging from 83% to 93%. A higher yield was obtained when pyrolysis was carried out with HZSM-5 at 400 degrees C and without catalysts, but at 600 and 800 degrees C. Formation of a significant amount of solid residue (about 13%) is observed using HUSY. The oily liquid product of pyrolysis, analysed by GC-MS and GC-FID, as well as by elemental analysis and for energy content, appeared lighter, less viscous and with a higher concentration of monoaromatics under catalytic condition, if compared to the liquid product derived from thermal degradation at the same temperature. HZSM-5 led to the production of a high yield of styrene (17.5%), while HUSY favoured the formation of ethylbenzene (15%). Energy released by combustion of the oil was around 39MJ/kg, thus suggesting the possibility to exploit it as a fuel, if the recovery of chemical compounds could not be realised. Elemental and proximate analysis of char and GC-TCD analysis of the gas were also performed. Finally, it was estimated to what extent these two products, showing a relevant ability to release energy, could fulfil the energy demand requested in pyrolysis. PMID- 27184450 TI - Lifecycle assessment of a system for food waste disposers to tank - A full-scale system evaluation. AB - An increased interest for separate collection of household food waste in Sweden has led to development of a number of different collection-systems - each with their particular benefits and drawbacks. In the present study, two systems for collection of food waste in households were compared; (a) use of food waste disposers (FWD) in kitchen sinks and (b) collection of food waste in paper bags for further treatment. The comparison was made in relation to greenhouse gas emissions as well as primary energy utilization. In both cases, collected food waste was treated through anaerobic digestion and digestate was used as fertilizer on farmland. Systems emissions of greenhouse gases from collection and treatment of 1ton of food waste (dry matter), are according to the performed assessment lower from the FWD-system compared to the reference system (-990 and 770kgCO2-eq./ton food waste dry matter respectively). The main reasons are a higher substitution of mineral nitrogen fertilizer followed by a higher substitution of diesel. Performed uncertainty analyses state that results are robust, but that decreasing losses of organic matter in pre-treatment of food waste collected in paper bags, as well as increased losses of organic matter and nutrients from the FWD-system could change the hierarchy in relation to greenhouse gas emissions. Owing to a higher use of electricity in the FWD-system, the paper bag collection system was preferable in relation to primary energy utilization. Due to the many questions still remaining regarding the impacts of an increased amount of nutrients and organic matter to the sewage system through an increased use of FWD, the later treatment of effluent from the FWD-system, as well as treatment of wastewater from kitchen sinks in the reference system, was not included in the assessment. In future work, these aspects would be of relevance to monitor. PMID- 27184449 TI - Polluted rainwater runoff from waste recovery and recycling companies: Determination of emission levels associated with the best available techniques. AB - Rainwater falling on outdoor storage areas of waste recovery and recycling companies becomes polluted via contact with the stored materials. It contains various pollutants, including heavy metals, polycyclic aromatic hydrocarbons and polychlorinated biphenyls, and is characterized by a highly fluctuating composition and flow rate. This polluted rainwater runoff is legally considered as industrial wastewater, and the polluting substances contained in the rainwater runoff at the point of discharge, are considered as emissions into water. The permitting authorities can set emission limit values (discharge limits) at the point of discharge. Best available techniques are an important reference point for setting emission limit values. In this paper, the emission levels associated with the best available techniques for dealing with polluted rainwater runoff from waste recovery and recycling companies were determined. The determination is based on an analysis of emission data measured at different companies in Flanders. The data show that a significant fraction of the pollution in rainwater runoff is associated with particles. A comparison with literature data provides strong indications that not only leaching, but also atmospheric deposition play an important role in the contamination of rainwater at waste recovery and recycling companies. The prevention of pollution and removal of suspended solids from rainwater runoff to levels below 60mg/l are considered as best available techniques. The associated emission levels were determined by considering only emission data from plants applying wastewater treatment, and excluding all samples with suspended solid levels >60mg/l. The resulting BAT-AEL can be used as a reference point for setting emission limit values for polluted rainwater runoff from waste recovery and recycling companies. Since the BAT-AEL (e.g. 150MUg/l for Cu) are significantly lower than current emission levels (e.g. 300MUg/l as the 90% percentile and 4910MUg/l as the maximum level for Cu), this will result in a significant reduction in emissions into water. PMID- 27184451 TI - Two novel temperate bacteriophages co-existing in Aeromonas sp. ARM81 - characterization of their genomes, proteomes and DNA methyltransferases. AB - Aeromonas species are causative agents of a wide spectrum of diseases in animals and humans. Although these bacteria are commonly found in various environments, little is known about their phages. Thus far, only one temperate Aeromonas phage has been characterized. Whole-genome sequencing of an Aeromonas sp. strain ARM81 revealed the presence of two prophage clusters. One of them is integrated into the chromosome and the other was maintained as an extrachromosomal, linear plasmid-like prophage encoding a protelomerase. Both prophages were artificially and spontaneously inducible. We separately isolated both phages and compared their genomes with other known viruses. The novel phages show no similarity to the previously characterized Aeromonas phages and might represent new evolutionary lineages of viruses infecting Aeromonadaceae. Apart from the comparative genomic analyses of these phages, complemented with their structural and molecular characterization, a functional analysis of four DNA methyltransferases encoded by these viruses was conducted. One of the investigated N6-adenine-modifying enzymes shares sequence specificity with a Dam like methyltransferase of its bacterial host, while another one is non-specific, as it catalyzes adenine methylation in various sequence contexts. The presented results shed new light on the diversity of Aeromonas temperate phages. PMID- 27184453 TI - Contents: Macromol. Rapid Commun. 10/2016. PMID- 27184452 TI - Shape and Interhelical Spacing of DNA Origami Nanostructures Studied by Small Angle X-ray Scattering. AB - Scaffolded DNA origami nanostructures enable the self-assembly of arbitrarily shaped objects with unprecedented accuracy. Yet, varying physiological conditions are prone to induce slight structural changes in the nanoscale architecture. Here, we report on high precision measurements of overall shape and interhelical distance of three prototypic DNA origami structures in solution using synchrotron small-angle X-ray scattering. Sheet-, brick-, and cylinder-shaped DNA constructs were assembled and the shape factors determined with angstrom resolution from fits to the scattering profiles. With decreasing MgCl2 concentration electrostatic swelling of both shape cross section and interhelical DNA spacing of the DNA origami structures is observed. The structures tolerate up to 10% interhelical expansion before they disintegrate. In contrast, with increasing temperature, the cylinder-shaped structures show no thermal expansion in a wide temperature window before they abruptly melt above 50 degrees C. Details on molecular structure of DNA origami can also be obtained using in-house X-ray scattering equipment and, hence, allow for routine folding and stability testing of DNA-based agents that are designed to operate under varying salt conditions. PMID- 27184454 TI - Macromol. Rapid Commun. 10/2016. AB - Back Cover: Sustainable polyamides with side groups and stereocenters are synthesized starting from L-menthone. This terpenoid ketone is transformed in a one-step synthesis into a chiral lactam, which is then polymerized via ring opening polymerization (ROP). The beneficial properties of these polymers are thus introduced via the structure and chirality of the lactam monomer. Further details can be found in the article by M. Winnacker*, M. Neumeier, X. Zhang, C. M. Papadakis, and B. Rieger on page 851. PMID- 27184456 TI - Physico-chemical and in vitro cellular properties of different calcium phosphate bioactive glass composite chitosan-collagen (CaP@ChiCol) for bone scaffolds. AB - In the present study, scaffolds for bone tissue engineering applications were made by immersing the inorganic phases of three different calcium phosphate (CaPs) (hydroxyapatite (HA), tricalcium phosphate (TCP), and biphasic calcium phosphate (BCP)) mixing bioactive glass (15Ca:80Si:5P) (BG) with polycaprolactone (PCL) as a binder in an organic phase of chitosan/collagen (ChiCol) matrix (CaPBG@ChiCol). Porous scaffolds were obtained by freeze drying the combinations. The mechanical properties and in vitro growth of rat osteoblast-like UMR-106 cells were investigated. The investigation indicated that the compressive strength was controlled by the types of CaP. The highest compressive modulus of the composites was 479.77 MPa (23.84 MPa for compressive strength) which is for the BCPBG@ChiCol composite. Compressive modulus of 459.01 and 435.95 MPa with compressive strength of 22.73 and 17.89 MPa were observed for the HABG@ChiCol and TCPBG@ChiCol composites, respectively. In vitro cell availability and proliferation tests confirmed the osteoblast attachment and growth on the CaPBG@ChiCol surface. Comparing the scaffolds, cells grown on the BCPBG based composite showed the higher cell density. To test its bioactivity, BCPBG@ChiCol was chosen for MTT and ALP assays on UMR-106 cells. The results indicated that the UMR-106 cells were viable and had higher ALP activity as the culturing times were increased. Therefore, ChiCol-fabricated BCPBG scaffold shows promise for bone regeneration. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1758-1766, 2017. PMID- 27184457 TI - Comparison of diagnostic accuracy of PCR and BACTEC with Lowenstein-Jensen culture and histopathology in the diagnosis of female genital tuberculosis in three subsets of gynaecological conditions. AB - The prevalence of female genital tuberculosis (FGTB) in India has been estimated to be about 19%. Despite an array of diagnostic tests being available, the goal of early diagnosis and treatment remains elusive. The present study was planned to identify better diagnostic tests for early detection of FGTB and also to compare their diagnostic accuracy with the existing standard diagnostic tests in three subsets of gynaecological conditions (infertility, menstrual abnormalities and pelvic inflammatory disease). Total of 90 patients recruited in three groups of 30 each underwent endometrial sampling. The biopsied tissue was sent for histopathological examination, AFB smear examination, culture in Lowenstein Jensen (L-J) and BACTEC 460 TB culture media and nested PCR testing. BACTEC had a sensitivity of 40% with a specificity of 90% while PCR showed a sensitivity and specificity of 62.5% and 54%, respectively, as compared to conventional methods (L-J culture or histopathology). Addition of PCR to BACTEC improved sensitivity from 40% to 52%. Hence, we conclude that combination of BACTEC and PCR had an improved detection as compared to conventional tests with an advantage of early results. PMID- 27184458 TI - Understanding the pathophysiology of schizophrenia: Contributions from the Melbourne Psychiatric Brain Bank. AB - The Melbourne Psychiatric Brain Bank came into existence 25years ago. This review focusses on lines of research that have used tissue from the Brain Bank over periods of time. Hence there is a discussion on the significance of changes in levels of serotonin 2A receptors in the cortex of patients with schizophrenia and the relevance of such changes with regards to the pathophysiology of the disorder. The extensive contribution made by studies using tissue from the Melbourne Psychiatric Brain Bank to understanding the role of muscarinic receptors in the pathophysiology and treatment of schizophrenia is summarised. Finally, findings using brain bank tissue and "omics" technologies are reviewed. In each case, findings using tissue from the Melbourne Psychiatric Brain Bank is placed in context with research carried out on human postmortem CNS in schizophrenia and with findings in other lines of research that can help explain the causes or consequences of changes in CNS molecular cytoarchitecture. This timely review of data from the Melbourne Psychiatric Brain Bank reinforces the challenges faced in trying to increase our understanding of the molecular pathophysiology of schizophrenia. Continuing to increase our understanding of the disorder is important as a precursor to identifying new drug targets that can be exploited to improve the treatment of a disorder where treatment resistance remains a significant problem (Millan et al., 2016). PMID- 27184459 TI - The organisation of spatial and temporal relations in memory. AB - Episodic memories are comprised of details of "where" and "when"; spatial and temporal relations, respectively. However, evidence from behavioural, neuropsychological, and neuroimaging studies has provided mixed interpretations about how memories for spatial and temporal relations are organised-they may be hierarchical, fully interactive, or independent. In the current study, we examined the interaction of memory for spatial and temporal relations. Using explicit reports and eye-tracking, we assessed younger and older adults' memory for spatial and temporal relations of objects that were presented singly across time in unique spatial locations. Explicit change detection of spatial relations was affected by a change in temporal relations, but explicit change detection of temporal relations was not affected by a change in spatial relations. Younger and older adults showed eye movement evidence of incidental memory for temporal relations, but only younger adults showed eye movement evidence of incidental memory for spatial relations. Together, these findings point towards a hierarchical organisation of relational memory. The implications of these findings are discussed in the context of the neural mechanisms that may support such a hierarchical organisation of memory. PMID- 27184460 TI - PEGylated niosomes-mediated drug delivery systems for Paeonol: preparation, pharmacokinetics studies and synergistic anti-tumor effects with 5-FU. AB - This work describes the preparation of a PEGylated niosomes-mediated drug delivery systems for Paeonol, thereby improving the bioavailability and chemical stability of Paeonol, prolonging its cellular uptake and enhancing its synergistic anti-cancer effects with 5-Fu. PEGylated niosomes, which are prepared from biocompatible nonionic surfactant of Spans 60 and cholesterol, and modified with PEG-SA. Pae-PEG-NISVs were evaluated in vitro and in vivo. The cytotoxicity of Pae-PEG-NISVs was investigated against HepG2 cells. Fluorescence microscope was used to detect the apoptotic morphological changes. Growth inhibition assays were carried out to investigate whether Pae-PEG-NISVs could enhance the antiproliferative effects of Pae co-treated with 5-FU on HepG2 cells. The optimized Pae-PEG-NISVs had mean diameters of approximately 166 nm and entrapment efficiency (EE) of 61.8%. Furthermore, the in vitro release study of Paeonol from PEGylated niosomes exhibited a relatively prolonged release profile for 12 h. Pharmacokinetic studies in rats after i.v. injection showed that Pae-PEG-NISVs had increased elimination half-lives (t1/2, 87.5 versus 17.0 min) and increased area under the concentration-time curve (AUC0-t, 38.0 versus 19.48 MUg/ml*min) compared to Paeonol solution. Formulated Paeonol had superior cytotoxicity versus the free drug with IC50 values of 22.47 and 85.16 MUg/mL at 24 h on HepG2 cells, respectively, and we found that low concentration of Pae-PEG-NISVs and 5-Fu in conjunction had obviously synergistic effect. Our results indicate that the PEG NISVs system has the potential to serve as an efficient carrier for Paeonol by effectively solubilizing, stabilizing and delivering the drug to the cancer cells. PMID- 27184462 TI - Cerebellar disruptions and neurodevelopmental disabilities. AB - The vulnerability of the cerebellum during prenatal life to disruptive events such as hemorrhage and infection leads to a wide variety of morphological abnormalities. This review discusses various prenatal cerebellar disruptions including cerebellar agenesis, unilateral cerebellar hypoplasia, cerebellar cleft, global cerebellar hypoplasia, and vanishing cerebellum in Chiari type II malformation. For each entity, we discuss the definition, potential pathomechanism, clinical findings including neurocognitive and behavioral problems, neuroimaging features, and management. Accurate recognition of cerebellar disruptions and their differentiation from malformations is important in terms of diagnosis, prognosis, and genetic counselling. PMID- 27184461 TI - Structure-function relationships in the developing cerebellum: Evidence from early-life cerebellar injury and neurodevelopmental disorders. AB - The increasing appreciation of the role of the cerebellum in motor and non-motor functions is crucial to understanding the outcomes of acquired cerebellar injury and developmental lesions in high-risk fetal and neonatal populations, children with cerebellar damage (e.g. posterior fossa tumors), and neurodevelopmental disorders (e.g. autism). We review available data regarding the relationship between the topography of cerebellar injury or abnormality and functional outcomes. We report emerging structure-function relationships with specific symptoms: cerebellar regions that interconnect with sensorimotor cortices are associated with motor impairments when damaged; disruption to posterolateral cerebellar regions that form circuits with association cortices impact long-term cognitive outcomes; and midline posterior vermal damage is associated with behavioral dysregulation and an autism-like phenotype. We also explore the impact of age and the potential role for critical periods on cerebellar structure and child function. These findings suggest that the cerebellum plays a critical role in motor, cognitive, and social-behavioral development, possibly via modulatory effects on the developing cerebral cortex. PMID- 27184464 TI - SNCA Gene Polymorphism may Contribute to an Increased Risk of Alzheimer's Disease. AB - BACKGROUND: The purpose of this study is to elucidate the association between alpha-synuclein (SNCA) polymorphisms and the risk of Alzheimer's disease (AD). METHODS: The PCR-RFLP was applied to detect SNCA gene rs6532190, rs3775430, and rs10516846 polymorphisms in 98 AD patients and 105 healthy elderly. RESULTS: The GG frequency of rs10516846 was evidently increased in AD group than control group (P < 0.05). There was a significant difference in SNCA level between the AD and control groups (P < 0.01). In the AD group, the SNCA level in cerebrospinal fluid of GG (rs10516846) carriers was increased as compared with AA carriers (P < 0.05). The GG (rs10516846) frequency of the early-onset AD group is significantly higher than that of the late-onset AD group (P < 0.05). The frequency of rs3775430 GG was lower in the early-onset group than that in the late-onset group (0% vs. 16.7%). The SNCA level in cerebrospinal fluid of GG (rs10516846) carriers in the early-onset AD group is higher than that of AA carriers (P < 0.05). CONCLUSION: SNCA gene polymorphism may be associated with an increased risk of AD and GG genotype of rs10516846 and elevated SNCA level in CSF may increase the risk of early-onset AD. PMID- 27184463 TI - Cardiovascular disease risk by assigned treatment using the 2013 and 1998 obesity guidelines. AB - OBJECTIVE: The 1998 and the 2013 guidelines on management of overweight and obesity in adults provided algorithms for identification of patients to be treated with weight loss. To date, the cardiovascular disease (CVD) risk in the groups recommended or not recommended for weight loss treatment has not been estimated and compared. METHODS: Baseline data for the Atherosclerosis Risk in Communities study were collected between 1987 and 1989 from adults aged 45 to 64 years. Black and White men and women free of CVD were followed over 22.8 years (median), and 2,907 incident CVD events were recorded. RESULTS: The hazard ratios adjusted for demographic variables in adults not recommended for treatment versus adults recommended for treatment were 0.54 (95% CI: 0.50-0.59) for the 1998 algorithm and 0.63 (95% CI: 0.58-0.69) for the 2013 algorithm, respectively. No gender or race differences were detected when the 2013 algorithm was applied, but using the 1998 algorithm, CVD risk between the groups recommended or not recommended for treatment was more pronounced in Black women than in Black men. CONCLUSIONS: The 2013 algorithm performed similarly in Black and White men and women but did not improve upon the 1998 algorithm in terms of discriminating risk of CVD. PMID- 27184466 TI - What Incentives Are Created by Medicare Payments for Total Hip Arthroplasty? AB - BACKGROUND: Differences in profitability and contribution margin (CM) between various patient populations may make certain patients particularly attractive (or unattractive) to providers. This study seeks to identify patient characteristics associated with increased profit and CM among Medicare patients undergoing total hip arthroplasty (THA). METHODS: The expected Medicare reimbursement for consecutive patients of Medicare-eligible age (65+ years) undergoing primary unilateral elective THA (n = 498) was calculated in accordance with Center for Medicare and Medicaid Services policy. Costs were derived from the hospital's cost accounting system. Profit and CM were calculated for each patient as reimbursement less total and variable costs, respectively. Patients were compared based on clinical and demographic factors by univariate and multivariate analyses. RESULTS: Medicare patients undergoing THA generated negative average profits but substantial positive CMs. Lower profit and CM were associated with higher American Society of Anesthesiologists Physical Status Classification (P < .01, P = .03), older age (P < .01), and longer length of stay (P < .01, P = .03). No association was found with gender, body mass index, or race. CONCLUSION: If our results are generalizable, Medicare patients requiring THA are currently financially attractive, but institutions have a long-term incentive to shift resources to more profitable patients and service lines, which may eventually restrict access to care for this population. THA providers have a financial incentive to favor Medicare patients with younger age, lower American Society of Anesthesiologists Physical Status Classification, and those who can be expected to require relatively short admissions. The Center for Medicare and Medicaid Services must strive to accurately match reimbursement rates to provider costs to avoid inequitable payments to providers and financial incentives discouraging treatment of high-risk patients or other patient subpopulations. PMID- 27184468 TI - Heat-enhanced peptide synthesis on Teflon-patterned paper. AB - In this report, we describe the methodology for 96 parallel organic syntheses of peptides on Teflon-patterned paper assisted by heating with an infra-red lamp. SPOT synthesis is an important technology for production of peptide arrays on a paper-based support for rapid identification of peptide ligands, epitope mapping, and identification of bio-conjugation reactions. The major drawback of the SPOT synthesis methodology published to-date is suboptimal reaction conversion due to mass transport limitations in the unmixed reaction spot. The technology developed in this report overcomes these problems by changing the environment of the reaction from static to dynamic (flow-through), and further accelerating the reaction by selective heating of the reaction support in contact with activated amino acids. Patterning paper with Teflon allows for droplets of organic solvents to be confined in a zone on the paper array and flow through the paper at a well defined rate and provide a convenient, power-free setup for flow-through solid phase synthesis and efficient assembly of peptide arrays. We employed an infra red (IR) lamp to locally heat the cellulosic support during the flow-through delivery of the reagents to each zone of the paper-based array. We demonstrate that IR-heating in solid phase peptide synthesis shortened the reaction time necessary for amide bond formation down to 3 minutes; in some couplings of alpha amino acids, conversion rates increased up to fifteen folds. The IR-heating improved the assembly of difficult sequences, such as homo-oligomers of all 20 natural amino acids. PMID- 27184467 TI - Area of Skin Numbness After Total Knee Arthroplasty: Does Minimally Invasive Approach Make Any Difference From Standard Approach? AB - BACKGROUND: Skin numbness after total knee arthroplasty (TKA) was reported in relation to injury of the infrapatellar branch of saphenous nerve (IPBSN). METHODS: Phase I study: A nonrandomized and nonconsecutive selection of 30 patients undergoing unilateral TKA, using minimally invasive surgery approach, and 30 patients having standard approach were included. Area of skin numbness was periodically evaluated and compared until 1-year follow-up (FU). Phase II study: we dissected 15 normal cadaveric knees and followed the course and distribution of IPBSN. RESULTS: Twenty-nine predominantly female patients in each group completed 1-year FU with no differences in demographic data. Both the groups had significantly improved Knee Society Score clinical and function scores with no statistical differences. The numb areas in both the groups similarly decreased from 2 weeks (51.7 cm2 vs 51.1 cm2) to 1 year (2.1 cm2 vs 2.4 cm2) with similar percentages of no skin numbness at 1 year (69% vs 65%). The IPBSN branched from saphenous nerve before exiting the adductor canal and ran longitudinally and obliquely. It was found as a single nerve in 20%, a 2-branch nerve in 67% and a 3 branch nerve in 13%. All branches crossed the knee midline between superior patellar pole and tibial tubercle. CONCLUSION: Clinical study showed that TKA using minimally invasive surgery approach provided similar area of skin numbness to standard approach. Numbness area gradually decreased at serial FUs in both the groups. The cadaveric study demonstrated that the IPBSN consistently gave no branch passing the knee midline above superior patellar pole. PMID- 27184465 TI - Guidewire and microcatheter utilization patterns during antegrade wire escalation in chronic total occlusion percutaneous coronary intervention: Insights from a contemporary multicenter registry. AB - OBJECTIVES: We sought to describe contemporary guidewire and microcatheter utilization for antegrade wire escalation (AWE) during chronic total occlusion (CTO) percutaneous coronary intervention (PCI). BACKGROUND: Equipment utilization for AWE has been variable and evolving over time. METHODS: We examined device utilization during 694 AWE attempts in 679 patients performed at 15 experienced US centers between May 2012 and April 2015. RESULTS: Mean age was 65.6 +/- 9.7 years, and 85% of the patients were men. Successful wiring occurred in 436 AWE attempts (63%). Final technical and procedural success was 91% and 89%, respectively. The mean number of guidewire types used for AWE was 2.2 +/- 1.4. The most frequently used guidewire types were the Pilot 200 (Abbott Vascular, 56% of AWE procedures), Fielder XT (Asahi Intecc, 45%), and the Confianza Pro 12 (Asahi Intecc, 28%). The same guidewires were the ones that most commonly crossed the occlusion: Pilot 200 (36% of successful AWE crossings), Fielder XT (20%), and Confianza Pro 12 (11%). A microcatheter or over-the-wire balloon was used for 81% of AWE attempts; the Corsair microcatheter (Asahi Intecc) was the most commonly used (44%). No significant association was found between guidewire type and incidence of major adverse cardiac events (MACE). CONCLUSIONS: Our contemporary, multicenter CTO PCI registry demonstrates that the most commonly used wires for AWE are polymer-jacketed guidewires. "Stiff" and polymer-jacketed guidewires appear to provide high crossing rates without an increase in MACE or perforation, and may thus be considered for upfront use. (c) 2016 Wiley Periodicals, Inc. PMID- 27184471 TI - Methyl iodine over oceans from the Arctic Ocean to the maritime Antarctic. AB - Studies about methyl iodide (CH3I), an important atmospheric iodine species over oceans, had been conducted in some maritime regions, but the understanding of the spatial distribution of CH3I on a global scale is still limited. In this study, we reports atmospheric CH3I over oceans during the Chinese Arctic and Antarctic Research Expeditions. CH3I varied considerably with the range of 0.17 to 2.9 pptv with absent of ship emission. The concentration of CH3I generally decreased with increasing latitudes, except for higher levels in the middle latitudes of the Northern Hemisphere than in the low latitudes. For sea areas, the Norwegian Sea had the highest CH3I concentrations with a median of 0.91 pptv, while the Central Arctic Ocean had the lowest concentrations with all values below 0.5 pptv. CH3I concentration over oceans was affected by many parameters, including sea surface temperature, salinity, dissolved organic carbon, biogenic emissions and input from continents, with distinctive dominant factor in different regions, indicating complex biogeochemical processes of CH3I on a global scale. PMID- 27184469 TI - Exciton Recombination, Energy-, and Charge Transfer in Single- and Multilayer Quantum-Dot Films on Silver Plasmonic Resonators. AB - We examine exciton recombination, energy-, and charge transfer in multilayer CdS/ZnS quantum dots (QDs) on silver plasmonic resonators using photoluminescence (PL) and excitation spectroscopy along with kinetic modeling and simulations. The exciton dynamics including all the processes are strongly affected by the separation distance between QDs and silver resonators, excitation wavelength, and QD film thickness. For a direct contact or very small distance, interfacial charge transfer and tunneling dominate over intrinsic radiative recombination and exciton energy transfer to surface plasmons (SPs), resulting in PL suppression. With increasing distance, however, tunneling diminishes dramatically, while long range exciton-SP coupling takes place much faster (>6.5 ns) than intrinsic recombination (~200 ns) causing considerable PL enhancement. The exciton-SP coupling strength shows a strong dependence on excitation wavelengths, suggesting the state-specific dynamics of excitons and the down-conversion of surface plasmons involved. The overlayers as well as the bottom monolayer of QD multilayers exhibit significant PL enhancement mainly through long-range exciton SP coupling. The overall emission behaviors from single- and multilayer QD films on silver resonators are described quantitatively by a photophysical kinetic model and simulations. The present experimental and simulation results provide important and useful design rules for QD-based light harvesting applications using the exciton-surface plasmon coupling. PMID- 27184470 TI - Bone marrow metastasis presenting as bicytopenia originating from hepatocellular carcinoma. AB - The bone is a common site for metastasis in hepatocellular carcinoma (HCC). However, bone marrow metastasis from HCC is rarely reported, and its frequency is unclear. Here we report a rare case of bone marrow metastasis that presented as bicytopenia originating from HCC without bone metastasis. A 58-year-old man was admitted for investigation of a liver mass with extensive lymph node enlargement that was detected when examining his general weakness and weight loss. Laboratory findings revealed anemia, thrombocytopenia, mild elevated liver enzymes, normal prothrombin time percentage and high levels of tumor markers (alpha-fetoprotein and des-gamma-carboxyprothrombin). Abdominal computed tomography showed multiple enhanced masses in the liver and multiple enlarged lymph nodes in the abdomen. A bone marrow biopsy revealed only a few normal hematopoietic cells and abundant tumor cells. Despite its rarity, bone marrow metastasis should always be suspected in HCC patients even if accompanied by cirrhosis. PMID- 27184474 TI - ML418: The First Selective, Sub-Micromolar Pore Blocker of Kir7.1 Potassium Channels. AB - The inward rectifier potassium (Kir) channel Kir7.1 (KCNJ13) has recently emerged as a key regulator of melanocortin signaling in the brain, electrolyte homeostasis in the eye, and uterine muscle contractility during pregnancy. The pharmacological tools available for exploring the physiology and therapeutic potential of Kir7.1 have been limited to relatively weak and nonselective small molecule inhibitors. Here, we report the discovery in a fluorescence-based high throughput screen of a novel Kir7.1 channel inhibitor, VU714. Site-directed mutagenesis of pore-lining amino acid residues identified glutamate 149 and alanine 150 as essential determinants of VU714 activity. Lead optimization with medicinal chemistry generated ML418, which exhibits sub-micromolar activity (IC50 = 310 nM) and superior selectivity over other Kir channels (at least 17-fold selective over Kir1.1, Kir2.1, Kir2.2, Kir2.3, Kir3.1/3.2, and Kir4.1) except for Kir6.2/SUR1 (equally potent). Evaluation in the EuroFins Lead Profiling panel of 64 GPCRs, ion-channels, and transporters for off-target activity of ML418 revealed a relatively clean ancillary pharmacology. While ML418 exhibited low CLHEP in human microsomes which could be modulated with lipophilicity adjustments, it showed high CLHEP in rat microsomes regardless of lipophilicity. A subsequent in vivo PK study of ML418 by intraperitoneal (IP) administration (30 mg/kg dosage) revealed a suitable PK profile (Cmax = 0.20 MUM and Tmax = 3 h) and favorable CNS distribution (mouse brain/plasma Kp of 10.9 to support in vivo studies. ML418, which represents the current state-of-the-art in Kir7.1 inhibitors, should be useful for exploring the physiology of Kir7.1 in vitro and in vivo. PMID- 27184475 TI - Evidence of benefits from using fresh and cryopreserved blood to transfuse patients with acute sickle cell disease. AB - BACKGROUND: The transfusion of red blood cell (RBC) concentrates is the main treatment for acute vaso-occlusive symptoms in sickle cell disease (SCD). Units of packed RBCs (pRBCs) must retain optimal characteristics for transfusion throughout the storage period. Transfused RBCs interact with the plasma and the endothelium that lines blood vessels and may be the target of immune-hematologic conflict if the patient produces antibodies against RBCs. Questions remain concerning the benefit-risk balance of RBC transfusions, in particular about the shelf-life of the units. STUDY DESIGN AND METHODS: Plasma samples from 33 hemoglobin SS patients with SCD who had severe acute-phase symptoms or were in steady-state were put in contact with 10 fresh-stored and older stored samples from the same 10 RBC units. The factors affecting RBC survival (phosphatidylserine exposure, cytosolic calcium influx, cell size reduction) were analyzed. RESULTS: We show that the effects of plasma samples from patients with SCD on pRBCs depend on the clinical condition of the patients and the duration of red cell storage. Signs of RBC senescence were correlated with the clinical status of the patient from whom the plasma sample was obtained. A decrease in RBC size and an increase in phosphatidylserine exposure were correlated with the duration of RBC storage. The behavior of cryopreserved pRBCs was similar to that of fresh refrigerated RBCs when challenged with patient plasma samples. CONCLUSION: The key points of this study are that the clinical condition of patients with SCD can negatively affect the integrity of pRBCs for transfusion, and those effects increase with longer storage. Also, cryopreserved pRBCs behave similarly to fresh RBCs when challenged with plasma samples from patients with SCD in acute phase. Our data provide the first evidence that fresh RBCs stored for short periods may be of greater benefit to patients with SCD than RBCs that have been refrigerated for longer periods, particularly for those who have acute symptoms of SCD. PMID- 27184476 TI - Determining jitter values in the very young by use of the e-norms methodology. AB - INTRODUCTION: The diagnosis of myasthenia gravis in very young infants is a challenging one. In young infants, stimulated single-fiber electromyography (StimSFEMG) is the most appropriate technique, but it has serious limitations due to the absence of reference values in this subpopulation. Here we present our efforts to derive a reference range of jitter in a patient cohort of infants <3 years of age using the extrapolated norms, or e-norms, technique. METHODS: The e norms method was used to calculate jitter mean consecutive difference (MCD) descriptive statistics for children <3 years of age. RESULTS: The e-norms derived jitter upper MCD limit was 45 MUs in children <1 year, 33 MUs in those <2 years, and 26 in those <3 years of age. CONCLUSION: In the absence of jitter reference values for the very young, the e-norms method can be used as an alternative to derive these values from laboratory cohorts. Muscle Nerve 55: 51-54, 2017. PMID- 27184477 TI - Mice with Dab1 or Vldlr insufficiency exhibit abnormal neonatal vocalization patterns. AB - Genetic and epigenetic changes in components of the Reelin-signaling pathway (RELN, DAB1) are associated with autism spectrum disorder (ASD) risk. Social communication deficits are a key component of the ASD diagnostic criteria, but the underlying neurogenetic mechanisms remain unknown. Reln insufficient mice exhibit ASD-like behavioral phenotypes including altered neonatal vocalization patterns. Reelin affects multiple pathways including through the receptors, Very low-density lipoprotein receptor (Vldlr), Apolipoprotein receptor 2 (Apoer2), and intracellular signaling molecule Disabled-1 (Dab1). As Vldlr was previously implicated in avian vocalization, here we investigate vocalizations of neonatal mice with a reduction or absence of these components of the Reelin-signaling pathway. Mice with low or no Dab1 expression exhibited reduced calling rates, altered call-type usage, and differential vocal development trajectories. Mice lacking Vldlr expression also had altered call repertoires, and this effect was exacerbated by deficiency in Apoer2. Together with previous findings, these observations 1) solidify a role for Reelin in vocal communication of multiple species, 2) point to the canonical Reelin-signaling pathway as critical for development of normal neonatal calling patterns in mice, and 3) suggest that mutants in this pathway could be used as murine models for Reelin-associated vocal deficits in humans. PMID- 27184479 TI - Frequent PIK3CA-activating mutations in hidradenoma papilliferums. AB - Hidradenoma papilliferum (HP) is a benign epithelial tumor most commonly seen in the vulva. It is proposed to be derived from the anogenital mammary-like glands and is histologically very similar to the mammary intraductal papilloma (IP). Approximately 60% of mammary IPs have activating mutations in either PIK3CA or AKT1, with each gene accounting for 30% of cases. In this study, we screened the mutation statuses of PIK3CA, AKT1, RAS, and BRAF in 30 HPs. The results showed that activating mutations in either PIK3CA or AKT1 were identified in 20 tumors (67%); 19 tumors had PIK3CA mutations (63%; 13 in exon 20 and 6 in exon 9), and 1 had an AKT1 E17K mutation (3%). BRAF V600E mutation was found in an HP that also had a PIK3CA H1047R mutation. No RAS mutation was found. The mutation status was not correlated with the degree of epithelial cell hyperplasia. We conclude that although there might be site-related variations in the mutation frequencies of PIK3CA and AKT1 genes, HP is histologically and also genetically very similar to the mammary IP, suggesting that HP can be viewed as the extramammary counterpart of mammary IP. PMID- 27184480 TI - Coexisting pituicytoma and pituitary adenoma; a second coincidence?-reply. PMID- 27184478 TI - Hodgkin lymphoma variant of Richter transformation: morphology, Epstein-Barr virus status, clonality, and survival analysis-with comparison to Hodgkin-like lesion. AB - Hodgkin/Reed-Sternberg (HRS) cells in the setting of chronic lymphocytic leukemia (CLL) exist in 2 forms: type I with isolated HRS cells in a CLL background (Hodgkin-like lesion) and type II with typical classic Hodgkin lymphoma, a variant of Richter transformation (CHL-RT). The clinical significance of the 2 morphological patterns is unclear, and their biological features have not been compared. We retrospectively reviewed 77 cases: 26 of type I and 51 of type II CHL-RT; 3 cases progressed from type I to type II. We examined clinical features, Epstein-Barr virus (EBV) status, and clonal relatedness after microdissection. Median age for type I was 62 years versus 73 years for type II (P=.01); 27% (type I) versus 73% (type II) had a history of CLL. HRS cells were positive for EBV in 71% (55/77), similar in types I and II. Clonality analysis was performed in 33 cases (type I and type II combined): HRS cells were clonally related to the underlying CLL in 14 and unrelated in 19. ZAP-70 expression of the CLL cells but not EBV status or morphological pattern was correlated with clonal relatedness: all 14 clonally related cases were ZAP-70 negative, whereas 74% (14/19) of clonally unrelated cases were ZAP-70 positive. Overall median survival (types I and II) after diagnosis was 44 months. Advanced age was an adverse risk factor for survival, but not histologic pattern, type I versus type II. HRS-like cells in a background of CLL carries a similar clinical risk to that of CHL-RT and may progress to classic Hodgkin lymphoma in some cases. PMID- 27184481 TI - Loss of INI1 expression in colorectal carcinoma is associated with high tumor grade, poor survival, BRAFV600E mutation, and mismatch repair deficiency. AB - SMARCB1 is a tumor suppressor gene that encodes for the protein INI1. SMARCB1 is commonly inactivated and INI1 correspondingly shows loss of expression in a range of malignant neoplasms including rhabdoid tumors, renal medullary carcinomas, and epithelioid sarcomas. Loss of INI1 expression has recently been reported in occasional gastrointestinal adenocarcinomas. We sought to investigate the incidence and clinicopathological significance of INI1 loss in colorectal adenocarcinoma (CRC). Immunohistochemistry for INI1 was performed in tissue microarray (TMA) format on a well-characterized and unselected cohort of CRCs undergoing surgical resection. If staining was negative or equivocal in the TMA sections, immunohistochemistry was repeated on whole sections. Focal or widespread negative staining for INI1 was identified in whole sections from 14 (0.46%) of 3051 CRCs. In 7 (50%) of 14 negative cases, the loss of staining was focal, whereas the remainder were characterized by negative staining in all neoplastic cells in whole sections. In the cases with focal staining, loss of staining was frequently found in areas of poor differentiation. Global or focal INI1 loss was strongly associated with higher histological grade, larger tumor size and poor overall survival (P<.001). We conclude that INI1 loss occurs rarely (0.46% when screened by TMA) in CRC, where it is associated with higher grade, larger tumor size, poorer survival, mismatch repair deficiency, and BRAFV600E mutation. PMID- 27184482 TI - Genomic copy number alterations in 33 malignant peritoneal mesothelioma analyzed by comparative genomic hybridization array. AB - Malignant peritoneal mesotheliomas (MPM) are rare, accounting for approximately 8% of cases of mesothelioma in France. We performed comparative genomic hybridization (CGH) on frozen MPM samples using the Agilent Human Genome CGH 180 K array. Samples were taken from a total of 33 French patients, comprising 20 men and 13 women with a mean (range) age of 58.4 (17-76) years. Asbestos exposure was reported in 8 patients (24.2%). Median (range) overall survival (OS) was 39 (0 119) months. CGH analysis demonstrated the presence of chromosomal instability in patients with MPM, with a genomic pattern that was similar to that described for pleural mesothelioma, including the loss of chromosomal regions 3p21, 9p21, and 22q12. In addition, novel genomic copy number alterations were identified, including the 15q26.2 region and the 8p11.22 region. Median OS was associated with a low peritoneal cancer index (P=.011), epithelioid subtype (P=.038), and a low number of genomic aberrations (P=.015), all of which constitute good prognostic factors for MPM. Our results provide new insights into the genetic and genomic background of MPM. Although pleural and peritoneal mesotheliomas have different risk factors, different therapeutics, and different prognosis; these data provide support to combine pleural and peritoneal mesothelioma in same clinical assays. PMID- 27184484 TI - Expression patterns of GATA3 and the androgen receptor are strongly correlated in patients with triple-negative breast cancer. AB - GATA-binding protein 3 (GATA3) is a diagnostically useful immunohistochemical marker of breast cancer. Because of its strong association with estrogen receptor expression, GATA3 has markedly reduced sensitivity in triple-negative breast cancer (TNBC). We constructed a tissue microarray using a large series of TNBCs and evaluated GATA3 expression by TNBC subtype as defined by surrogate immunohistochemical markers. A total of 205 TNBCs were classified into cancers of the molecular apocrine type (n=23, 11.2%), claudin-low type (n=21, 10.2%), basal like type (n=91, 44.4%), mixed type (n=62, 30.2%), and null type (n=8, 3.9%). The GATA3 scores (staining intensity * proportion) were categorized as negative (0), focally positive (1-10), or positive (11-300). GATA3 staining was negative in 153 cancers (74.6%), focally positive in 11 (5.4%), and positive in 41 (20.0%). The rate of focal positivity or positivity for GATA3 was significantly higher in the molecular apocrine type (73.9%, 17/23) than in other types of TNBCs (P=.001). The mean GATA3 score of molecular apocrine-type TNBC was significantly higher than that of the other types (P=.001) and differed significantly between androgen receptor (AR)-positive and AR-negative TNBCs (P<.001). In conclusion, GATA3 expression was correlated strongly with AR-positive, molecular apocrine-type TNBCs. Co-expression of AR and GATA3 is a specific feature of molecular apocrine type TNBC, which may serve as a diagnostic aid for cancer of unknown primary. PMID- 27184483 TI - Hepatocyte differentiation markers in adenocarcinoma of the prostate: hepatocyte paraffin 1 but not arginase-1 is specifically expressed in a subset of prostatic adenocarcinoma. AB - Prostate adenocarcinoma and hepatocellular carcinoma (HCC) are common cancer types. Both may present with bone metastases, and both are known to be CK7/CK20 negative. Thus, diagnosis of less well-differentiated tumors at metastatic sites essentially relies on immunohistochemical confirmation. However, insufficient data exist on the expression status of the main 2 hepatocyte markers hepatocyte paraffin 1 (HepPar-1) and arginase-1 (Arg-1) in prostatic adenocarcinoma. We screened 557 prostate carcinoma cases for expression of these 2 markers using tissue microarrays. Sixty-four of 557 (11.5%) cases showed highly variable expression of HepPar-1 in 1% to 75% of tumor cells with a characteristically strong granular "mitochondrial" pattern. Only 13 cases (2.3%) expressed HepPar-1 in greater than 10% of the tumor cells. No correlation was seen with Gleason grade. On the other hand, 19 (3.4%) of 557 cases showed variable nonspecific cytoplasmic expression of Arg-1 distinct from the specific combined nucleocytoplasmic staining seen in normal liver and in HCC. Specifically, this Arg-1 pattern was seen only using one antibody lot and not another suggesting cross-reactivity. Only a single case showed specific nucleocytoplasmic expression of Arg-1 in the tumor cells. In conclusion, specific granular cytoplasmic staining for HepPar-1 is frequent in prostatic adenocarcinomas (11.5%) but usually focal and limited to less than 5% of tumor cells. This should not be misinterpreted as evidence of HCC, particularly in solid-pattern neoplasms. On the other hand, specific Arg-1 expression is very rare (0.18%), highlighting the value of Arg-1 in distinguishing HepPar-1-positive prostatic carcinoma from HCC at metastatic sites or in cases of liver metastasis from prostate carcinoma. PMID- 27184485 TI - Teaching Not-Knowing: Strategies for Cultural Competence in Psychotherapy Supervision. PMID- 27184486 TI - Bortezomib-based induction improves progression-free survival of myeloma patients harboring 17p deletion and/or t(4;14) and overcomes their adverse prognosis. AB - Providing a risk-adapted treatment strategy has been a key goal in the ongoing research efforts aimed at providing treatment tailored to the individual genetic make-up. Eighty myeloma patients have been tested for presence of 17p deletion and/or t(4;14) by fluorescent in situ hybridization (FISH). Based on FISH results, they have been categorized into patients lacking them (standard risk) and those harboring them (high risk). Patients in each category were randomly assigned 1:1 to induction treatment by either vincristine, adriamycin and dexamethasone (VAD), or bortezomib and dexamethasone (VD) followed by autologous stem cell transplantation and thalidomide maintenance and were followed up for 32 months. 32.5 % of patients were high risk. Following induction, there were significantly higher rates of at least very good partial response achievement in VD arms in standard- and high-risk patients. Regarding complete response achievement, there were insignificant differences between VAD and VD arms in standard and high-risk patients. After a median follow-up of 17.5 months, there was insignificant difference in overall survival (OS) between VAD and VD arms in standard and high-risk patients. There was superior progression-free survival (PFS) in VD arms in standard- and high-risk patients. Among patients who received VD, those belonging to standard and high-risk groups had similar PFS. In conclusion, bortezomib-based induction is superior to non-bortezomib-based one in patients harboring 17p deletion and/or t(4;14) in terms of improving PFS but not OS. Also, it reduces progression risk in patients harboring these high risk cytogenetics. PMID- 27184487 TI - In vivo structural and cellular remodeling of engineered bone-ligament-bone constructs used for anterior cruciate ligament reconstruction in sheep. AB - Anterior cruciate ligament (ACL) ruptures rank among the most prevalent and costly sports-related injuries. Current tendon grafts used for ACL reconstruction are limited by suboptimal biomechanical properties. We have addressed these issues by engineering multiphasic bone-ligament-bone (BLB) constructs that develop structural and mechanical properties similar to native ACL. The purpose of this study was to examine the acute remodeling process that occurs as the BLB grafts advance toward the adult ligament phenotype in vivo. Thus, we implanted BLB constructs fabricated from male cells into female host sheep and allowed 3, 7, 14, or 28 days (n = 4 at each time point) for recovery. To address whether or not graft-derived cells were even necessary, a subset of BLB constructs (n = 3) were acellularized, implanted, and allowed 28 days for recovery. At each recovery time point, the following histological analyses were performed: picrosirius red staining to assess collagen alignment and immunohistochemistry to assess both graft development and host immune response. Polymerase chain reaction (PCR) analysis, performed on every explanted BLB, was used to detect the presence of graft-derived male cells remaining in the constructs and/or migration into surrounding host tissue. The analysis of the PCR and histology samples revealed a rapid migration of host-derived macrophages and neutrophils into the graft at 3 days, followed by increased collagen density and alignment, vascularization, innervation, and near complete repopulation of the graft with host cells within 28 days. This study provides a greater understanding of the processes of ligament regeneration in our BLB constructs as they remodel toward the adult ligament phenotype. PMID- 27184488 TI - Impact of sink location on hand hygiene compliance after care of patients with Clostridium difficile infection: a cross-sectional study. AB - BACKGROUND: The impact of sink location on hand washing compliance after contact with patients with Clostridium difficile infection (CDI) is poorly understood. The aim of this study is to determine the location of hand wash sinks available to healthcare workers (HCWs) after caring for patients with CDI and to assess the impact on hand washing compliance. METHODS: We performed a cross-sectional study in a 637-bed tertiary care hospital, Canada. HCW hand hygiene compliance after contact with CDI patients was measured through direct unobtrusive observations. Location of sinks in relation with the patients' rooms was assessed on the day of diagnosis. Predictors of compliance were assessed through univariate and multivariate logistic regression. RESULTS: 247 hand hygiene opportunities following care of a CDI patient were observed. Glove use compliance was 85.4 % (211/247), but hand washing compliance after care of CDI patients was only 14.2 % (35/247). Hand rubbing was performed instead of hand washing in 33.2 % of opportunities (82/247). The median distance between the patient zone of CDI patients and the nearest sink was 13.1 m (interquartile range, 7.6-23.2). Sinks were directly visible upon exiting the patient's room on only 33.2 % (82/247) occasions. By multivariate analysis, an increasing distance between the patient zone and the nearest sink was inversely associated with hand washing compliance (adjusted OR, 0.90, 95 % CI, 0.84-0.97; P = 0.008), while proper timing of glove removal upon leaving the patient zone was directly associated with hand washing compliance (adjusted OR, 14.87; 95 % CI, 1.93-114.43; P = 0.01). CONCLUSIONS: Hand washing compliance following contact with patients with C. difficile infections was low. Poor access to sinks is associated with decreased hand washing compliance. Improvement strategies are urgently needed. PMID- 27184489 TI - Retinal pigment epithelial atrophy over polypoidal choroidal vasculopathy lesions during ranibizumab monotherapy. AB - BACKGROUND: To evaluate the quantitative changes of retinal pigment epithelial (RPE) atrophy during 3-year follow-up period of ranibizumab monotherapy for polypoidal choroidal vasculopathy (PCV). METHODS: We retrospectively reviewed consecutive 100 Japanese patients with unilateral symptomatic treatment-naive PCV who received ranibizumab monotherapy for 3 years. Color fundus photography, spectral-domain optical coherence tomography, and fundus autofluorescence were evaluated for RPE atrophy. Multiple regression analysis was performed to investigate the predictive factors found during univariate analysis to identify an association with increased RPE atrophic areas. RPE atrophic areas overlapping PCV lesions were measured. RESULTS: The mean (standard deviation) number of injections was 11.4 (4.50). RPE atrophic area enlarged to 2.91 (5.41 mm(2)) 3 years after the first injection from 1.22 (1.72 mm(2)) at baseline, which differed significantly (P = 0.012). Multiple regression analysis showed that larger PCV lesions and larger RPE atrophic areas at baseline were associated with increased RPE atrophic areas. RPE atrophic area overlapping the baseline PCV lesions significantly increased during 3-year follow-up period, whereas RPE atrophic area not overlapping the baseline PCV lesions did not increase significantly. CONCLUSION: RPE atrophy progresses in eyes with PCV during ranibizumab monotherapy and the tendency for development of RPE atrophy within the PCV lesions. PMID- 27184490 TI - Dandy-Walker Cyst Presenting as Congenital Scalp Swelling. PMID- 27184493 TI - Emerging Trends in Biomaterials Research. PMID- 27184491 TI - The Immune Revolution in Gastrointestinal Tumours: Leading the Way or Just Following? AB - The encouraging results in immunotherapy for melanoma also led the way for translational and clinical research about immune-related mechanisms possibly relevant for gastrointestinal tumours. It is in fact now evident that the immune checkpoint modulation and in particular cell-mediated immune-response through programmed cell death-1 (PD-1) and the cytotoxic T-lymphocyte antigen-4 (CTLA4) receptors along with the regulatory T cells activity all have a relevant role in gastrointestinal cancers as well. This review aims to explore the state of the art of immunotherapy for gastrointestinal tumours, deepening recent scientific evidence regarding anti PD-1/PDL-1 and anti CTLA4 monoclonal antibodies, peptide based vaccine, DNA based vaccine, and pulsed dendritic cells, either alone or in combination with other antineoplastic medical therapy and locoregional treatments. Considering the non-negligible toxicity profile deriving from such a treatment approach, predictive biomarkers of response to immunotherapy in gastrointestinal cancer are also urgently needed in order to better select the patients' group with the highest likelihood of benefit. PMID- 27184492 TI - Will Testicular Germ Cell Tumors Remain Untargetable? AB - Testicular Germ cell tumors (TGCT) represent the most common solid tumors affecting young men. They constitute a distinct entity because of their embryonic origin and their unique biological behavior. Recently, new preclinical data on genetic and epigenetic susceptibility profiles, biological signaling machinery as well as on molecular patterns of tumors and pathways of pathogenesis helped to elucidate the pathogenesis and the differentiation of TGCTs and to understand the mechanisms behind the development of resistance to treatment. In the present work, we have reviewed new clues to the development, differentiation and progression of TGCTs. We focus on the most important epigenetic and molecular biomarkers, and discussed their diagnostic and prognostic accuracy compared to the currently used biomarkers. The mechanisms underlying the development of resistance to cisplatin and commonly used chemotherapeutic agents are also discussed in detail. Finally, we summarize failed and ongoing clinical trials using targeted therapies in resistant TGCTs, and analyze the potential of new targeted therapies. PMID- 27184494 TI - Advanced Bioinks for 3D Printing: A Materials Science Perspective. AB - Advanced bioinks for 3D printing are rationally designed materials intended to improve the functionality of printed scaffolds outside the traditional paradigm of the "biofabrication window". While the biofabrication window paradigm necessitates compromise between suitability for fabrication and ability to accommodate encapsulated cells, recent developments in advanced bioinks have resulted in improved designs for a range of biofabrication platforms without this tradeoff. This has resulted in a new generation of bioinks with high print fidelity, shear-thinning characteristics, and crosslinked scaffolds with high mechanical strength, high cytocompatibility, and the ability to modulate cellular functions. In this review, we describe some of the promising strategies being pursued to achieve these goals, including multimaterial, interpenetrating network, nanocomposite, and supramolecular bioinks. We also provide an overview of current and emerging trends in advanced bioink synthesis and biofabrication, and evaluate the potential applications of these novel biomaterials to clinical use. PMID- 27184495 TI - Impact of teneligliptin on oxidative stress and endothelial function in type 2 diabetes patients with chronic kidney disease: a case-control study. AB - BACKGROUND: The aim of the present study was to elucidate the effect of teneligliptin on oxidative stress and endothelial function in Japanese patients with type 2 diabetes and chronic kidney disease (CKD). METHODS: Forty-five patients with type 2 diabetes and CKD who received sitagliptin for at least 12 months were randomized to either continue sitagliptin (n = 23) or switch to teneligliptin (n = 22) for 24 weeks. The following parameters were evaluated at baseline and after 24 weeks of treatment with continued sitagliptin or teneligliptin: blood pressure, haemoglobin A1c (HbA1c), estimated glomerular filtration rate (eGFR), urinary albumin excretion, endothelial function by reactive hyperaemia index (RHI; EndoPAT((r)) system), reactive oxygen metabolites (ROMs) measured by the d-ROMS test, 8-hydroxy-2'-deoxyguanosine, urinary liver type fatty acid binding protein (L-FABP), and urinary 8-isoprostane. RESULTS: The two groups did not significantly differ with regard to age, male-to-female ratio, duration of diabetes, body mass index, HbA1c, eGFR, or urinary albumin excretion levels at baseline. We found no significant differences in changes of HbA1c, eGFR, or urinary albumin excretion levels between the two groups after 24 weeks of treatment. However, treatment with teneligliptin, but not sitagliptin, significantly improved RHI values and was correlated with the percent changes in RHI and d-ROMs. CONCLUSIONS: The present study demonstrated that teneligliptin, can improve endothelial function and reduce renal and vascular oxidative stress in patients with type 2 diabetes and CKD, independently of reducing albuminuria or improving glucose control. Trial registration UMIN000017180. PMID- 27184496 TI - Cost-effectiveness of tolvaptan for the treatment of hyponatraemia secondary to syndrome of inappropriate antidiuretic hormone secretion in Sweden. AB - BACKGROUND: Tolvaptan is the only vasopressin V2 receptor antagonist licensed by the European Medicines Agency for the treatment of hyponatraemia (HN) secondary to the syndrome of inappropriate antidiuretic hormone secretion (SIADH). We have investigated the cost-effectiveness of tolvaptan versus no active treatment (NAT) in adult patients within the licensed indication who have either failed to respond to fluid restriction or for whom the use of fluid restriction is not suitable, from the societal perspective in Sweden. METHODS: A cost-utility analysis, considering a 'general SIADH' population and two subpopulations of patients (small-cell lung cancer [SCLC] and pneumonia) to broadly represent the complex clinical pathway of SIADH, was performed. A discrete event simulation was developed to model the progression of individuals through inpatient admissions over a 30-day time horizon (180 days for the SCLC cohort). Clinical data were derived from tolvaptan trials and observational data sources. All costs are given in Swedish kronor (SEK). RESULTS: In the 'general SIADH' population, tolvaptan was associated with reduced costs (SEK 5,779 per patient [?624]) and increased quality-adjusted life-years (QALYs) (0.0019) compared with NAT and was therefore the dominant treatment strategy. Tolvaptan was also associated with reduced costs and increased QALYs in the SCLC and pneumonia subpopulations. The most influential variables in our analysis were reduction in hospital length of stay, duration of treatment and long term treatment with tolvaptan in SCLC patients. CONCLUSIONS: Tolvaptan represents a cost-effective treatment option in Sweden for hospitalised patients with HN secondary to SIADH who have either failed to respond to or are unsuitable for fluid restriction. PMID- 27184497 TI - Acute myocardial infarction in a young bodybuilder taking anabolic androgenic steroids: A case report and critical review of the literature. AB - We describe a case report of a 30-year-old bodybuilder suffering acute myocardial infarction (AMI). He had been taking stanozolol and testosterone for two months. The coronary angiogram showed high thrombotic burden in the left anterior descending artery without underlying atherosclerosis. Few case reports of AMI in athletes taking anabolic androgenic steroids (AASs) have been reported so far. AAS-related AMI is possibly underreported in the medical literature due to the desire of the affected individuals to hide AAS use. Physicians should always consider the possibility of AAS abuse in the context of a young athlete suffering AMI. AASs can predispose to AMI through the acceleration of coronary atherosclerosis. Additionally, thrombosis without underlying atherosclerosis or vasospasm is highly possible to cause AMI in AAS users. Complications after AMI may be more frequent in AAS users. PMID- 27184498 TI - alpha-Lactalbumin: Of Camels and Cows. AB - Since camel milk has been attributed with various medicinal properties not found in bovine milk, we are systematically examining the differences between different proteins in bovine and camel milk. The purpose of this study is to investigate the structural differences between the bovine and camel alpha- lactalbumins. alpha-Lactalbumin is a highly abundant protein present in the milk of all mammalian species. Here we found several structural differences between bovine and camel alpha-lactalbumins: camel protein is more stable towards thermal and pHmediated denaturation but less stable towards guanidine hydrochloride-mediated unfolding, aggregates faster and is predicted to be more disordered than bovine alpha- lactalbumin. PMID- 27184499 TI - Evaluation of Moringa oleifera Seed Lectin as a Metal Remover in Aqueous Solutions. AB - The efficacy of Moringa oleifera seed lectin (WSMoL) as a metal remover in water and the effects of metals on its hemagglutinating and antibacterial activities were determined. Aqueous metal solutions were incubated with WSMoL for 8 h at 4 degrees C and the concentrations of metals were determined using atomic absorption spectroscopy. Hemagglutination and antibacterial assays were conducted with WSMoL and lectin exposed or not to the metals. The removal efficiency of WSMoL was 49.00%, 53.21%, 71.45%, 55.42%, 69.88%, 62.14%, and 49.36% for Cd+2, Pb+2, Cu+2, Zn+2, Mg+2, Mn+2, and Al+3, respectively. WSMoL showed bacteriostatic and bactericidal activities against Escherichia coli and Salmonella enterica serovar Enteritidis. However, hemagglutinating and antibacterial activities were impaired after exposure to metals. In conclusion, WSMoL efficiently removed metals present in water but the interaction with metals impaired lectin carbohydrate-binding ability and antibacterial activity. This should be considered when properties of WSMoL other than metal removal are desired. PMID- 27184500 TI - Anosmin 1 Interacts with the Prokineticin Receptor 2 In Vitro Indicating a Molecular Link Between Both Proteins in the Pathogenesis of Kallmann Syndrome. AB - Sexual maturation and olfactory bulb defects found in prokineticin 2 (Pk2) and prokineticin receptor 2 (Pkr2) mutant mice resembling the phenotypic characteristics of Kallmann syndrome (KS), gave rise to the question of whether these genes would have a role in KS pathogenesis. Later, mutations in both genes were identified in patients suffering from KS. The gene responsible for the Xlinked form of KS, ANOS1, encodes the ECM protein anosmin 1. Among other functions, anosmin 1 can regulate the activity of FGFR1, encoded by one of the genes involved in the autosomal transmission of KS. Therefore, it has been proposed that anosmin 1 could interact with PKR2 to modulate its activity. We present the first evidence supporting this hypothesis and report the interaction of full-length anosmin 1 with three extracellular domains of PKR2. A truncated anosmin 1 protein comprising the first three domains of the protein interacts with the second extracellular loop of PKR2, involved in PK2 binding. Finally, last three FnIII repeats of anosmin 1 also interacted with the PKR2 domains that interacted with full-length anosmin 1. Our data represent a molecular link between two of the genes involved in KS pathogenesis. PMID- 27184501 TI - Two patients with chromosome 22q11.2 deletion presenting with childhood obesity and hyperphagia. AB - Chromosome 22q11.2 deletion syndrome is a clinically heterogeneous condition of intellectual disability, parathyroid and thyroid hypoplasia, palatal abnormalities, cardiac malformations and psychiatric symptoms. Hyperphagia and childhood obesity is widely reported in Prader-Willi Syndrome (PWS) but there is only one previous report of this presentation in chromosome 22q11.2 deletion syndrome. We describe two further cases of chromosome 22q11.2 deletion syndrome in which hyperphagia and childhood obesity were the presenting features. This may be a manifestation of obsessive behaviour secondary to some of the psychiatric features commonly seen in chromosome 22q11.2 deletion syndrome. Serious complications may result from hyperphagia and childhood obesity therefore early recognition and intervention is crucial. Due to the similar clinical presentation of these two patients to patients with PWS, it is suggested that the hyperphagia seen here should be managed in a similar way to how it is managed in PWS. PMID- 27184503 TI - Sorption and desorption of organic matter on solid-phase extraction media to isolate and identify N-nitrosodimethylamine precursors. AB - #x02010;Nitrosodimethylamine is mutagenic in rodents, a drinking water contaminant, and a byproduct of drinking water disinfection by chloramination. Nitrosodimethylamine precursor identification leads to their control and improved understanding of nitrosodimethylamine formation during chloramination. Mass balances on nitrosodimethylamine precursors were evaluated across solid-phase extraction cartridges and in eluates to select the best combination of solid phase media and eluent that maximized recovery of nitrosodimethylamine precursors into a solvent amenable to time-of-flight mass spectrometry analysis. After reviewing literature and comparing various solid-phase cartridges and eluent combinations, a method was obtained to efficiently recover nitrosodimethylamine precursors. The approach with the greatest recoveries of nitrosodimethylamine precursors involved cation exchange resin loaded with water samples at pH 3 and eluted with 5% NH4 OH in methanol. This indicated that nitrosodimethylamine precursors are amines that protonate at low pH and deprotonate at high pH. Quaternary amines were irreversibly sorbed to the cation exchange cartridge and did not account for a large fraction of precursors. Overall, a median recovery of 82% for nitrosodimethylamine precursors was achieved from 11 surface waters and one wastewater. Applying this method allowed discovery of methadone as a new nitrosodimethylamine precursor in wastewater effluent and drinking water treatment plant intakes. PMID- 27184502 TI - Identification of novel mutations in CD2BP1 gene in clinically proven rheumatoid arthritis patients of south India. AB - Pyogenic Arthritis, Pyoderma gangrenosum, and Acne (PAPA syndrome) is a rare autosomal dominant, auto-inflammatory disease that affects joints and skin. The disease results due to mutations in the cluster of differentiation 2 binding protein 1 (CD2BP1) gene on chromosome 15q24.3. Rheumatoid arthritis (RA) is a common, genetically complex disease that affects the joints with occasional skin manifestations. Studies related to the pathophysiology of inflammation in these two disorders show a certain degree of overlap at genetic level. The present study was done to confirm the existence of such a genetic overlap between PAPA syndrome and RA in south Indian population. In the present study 100 patients who were clinically diagnosed rheumatoid arthritis and 100 apparently healthy controls were chosen and the 15 exons of CD2BP1 gene were PCR-amplified and sequenced. The sequence analysis showed that in exon 3 thirty eight patients revealed presence of novel heterozygous missense mutations p.Glu51Asp, p.Leu57Arg and p.Ala64Thr. In exons 6, 10 and 14 eight patients showed 44 novel missense mutations and two patients showed novel frame shift mutations p.(Met123_Leu416delinsThr) and p.(Thr337Profs*52) leading to truncated protein formation. Such mutations were not seen in controls. Further, the in silico analysis revealed the mutant CD2BP1 structure showed deletion of Cdc15 and SH3 domains when superimposed with the wild type CD2BP1 structure with variable RMSD values. Therefore, these structural variations in CD2BP1 gene due to the mutations could be one of the strongest reasons to demonstrate the involvement of these gene variations in the patients with rheumatoid arthritis. PMID- 27184504 TI - Dimethyl fumarate ameliorates dextran sulfate sodium-induced murine experimental colitis by activating Nrf2 and suppressing NLRP3 inflammasome activation. AB - In the present study, we examined the effects of dimethyl fumarate (DMF) on dextran sulfate sodium (DSS)-induced murine colitis, an animal model which mimics human IBD. Oral administration of DMF dose-dependently attenuated body weight loss, colon length shortening and colonic pathological damage including decreased myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) activities in DSS-treated mice. Increased glutathione (GSH) induced by DMF demonstrated its potential antioxidant capacity. In addition, Nrf2 and its downstream genes were markedly activated by DMF. Furthermore, protein and mRNA levels of pro inflammatory cytokines, including IL-1beta, TNF-alpha and IL-6 were markedly suppressed by DMF. At the same time, decreased activation of caspase-1 was detected in DMF-treated mice, indicating that the NLRP3 inflammasome activation was suppressed. The in vitro study verified a negative regulation of DMF and its intestinal metabolite on NLRP3 inflammasome. Moreover, the inhibitory effect was found to be mostly dependent on Nrf2 which decreased mitochondrial ROS (mROS) generation and mitochondrial DNA (mtDNA) release. Taken together, our results demonstrated the ability of DMF to inhibit NLRP3 inflammasome activation and its potential use in the treatment of NLRP3-associated diseases. PMID- 27184506 TI - Sinusitis in patients undergoing allogeneic bone marrow transplantation - a review. AB - INTRODUCTION: Sinusitis is a common morbidity in general population, however little is known about its occurrence in severely immunocompromised patients undergoing allogeneic hematopoietic stem cell transplantation. OBJECTIVE: The aim of the study was to analyze the literature concerning sinusitis in patients undergoing allogeneic bone marrow transplantation. METHODS: An electronic database search was performed with the objective of identifying all original trials examining sinusitis in allogeneic hematopoietic stem cell transplant recipients. The search was limited to English-language publications. RESULTS: Twenty five studies, published between 1985 and 2015 were identified, none of them being a randomized clinical trial. They reported on 31-955 patients, discussing different issues i.e. value of pretransplant sinonasal evaluation and its impact on post-transplant morbidity and mortality, treatment, risk factors analysis. CONCLUSION: Results from analyzed studies yielded inconsistent results. Nevertheless, some recommendations for good practice could be made. First, it seems advisable to screen all patients undergoing allogeneic hematopoietic stem cell transplantation with Computed Tomography (CT) prior to procedure. Second, patients with symptoms of sinusitis should be treated before hematopoietic stem cell transplantation (HSCT), preferably with conservative medical approach. Third, patients who have undergone hematopoietic stem cell transplantation should be monitored closely for sinusitis, especially in the early period after transplantation. PMID- 27184505 TI - Functional Assessment of Bioprosthetic Aortic Valves by CMR. AB - OBJECTIVES: The aim of this study was to evaluate cardiac magnetic resonance (CMR) phase-contrast (PC) measures of a bioprosthetic aortic valve velocity time integral (PC-VTI) to derive the effective orifice area (PC-EOA) and to compare these findings with the clinical standard of Doppler echocardiography. BACKGROUND: Bioprosthetic aortic valve function can be assessed with CMR planimetry of the anatomic orifice area and PC measurement of peak transvalvular systolic velocity. However, bioprosthetic valves can create image artifact and data dropout, which makes planimetry measures a challenge for even experienced CMR readers. METHODS: From our institutional database, we identified 38 patients who had undergone 47 paired imaging studies (CMR and Doppler) within 46 days (median 3 days). Transvalvular forward flow volume by CMR was determined by 3 methods: ascending aorta flow, transvalvular flow, and left ventricular stroke volume. PC-EOA was derived as flow divided by PC-VTI, calculated with a semiautomated MATLAB (Mathworks, Natick, Massachusetts) application for integration of the instantaneous peak transvalvular velocity. Doppler EOA was assessed by the continuity method. RESULTS: PC-EOA by all 3 flow approaches demonstrated a strong correlation with Doppler EOA (r = 0.949, 0.947, and 0.874, respectively; all p < 0.001) and revealed good agreement (bias = 0.03, 0.03, and 0.28 cm(2), respectively). With Doppler-derived EOA as the reference standard, CMR was able to correctly characterize 24 of 26 valves as normal (EOA >1.2 cm(2)), 12 of 14 possibly stenotic valves (0.8 < EOA < 1.2 cm(2)), and 5 of 7 stenotic valves (EOA <0.8 cm(2); k = 0.826). CONCLUSIONS: We describe a new CMR based method to derive the EOA for bioprosthetic aortic valves. This method compares favorably to traditional Doppler methods and might be an important additional parameter in the evaluation of prosthetic valves by CMR, particularly when Doppler methods are suboptimal or considered discordant with the clinical presentation. PMID- 27184507 TI - Obstructive sleep apnea and oral language disorders. AB - INTRODUCTION: Children and adolescents with obstructive sleep apnea (OSA) may have consequences, such as daytime sleepiness and learning, memory, and attention disorders, that may interfere in oral language. OBJECTIVE: To verify, based on the literature, whether OSA in children was correlated to oral language disorders. METHODS: A literature review was carried out in the Lilacs, PubMed, Scopus, and Web of Science databases using the descriptors "Child Language" AND "Obstructive Sleep Apnea". Articles that did not discuss the topic and included children with other comorbidities rather than OSA were excluded. RESULTS: In total, no articles were found at Lilacs, 37 at PubMed, 47 at Scopus, and 38 at Web of Science databases. Based on the inclusion and exclusion criteria, six studies were selected, all published from 2004 to 2014. Four articles demonstrated an association between primary snoring/OSA and receptive language and four articles showed an association with expressive language. It is noteworthy that the articles used different tools and considered different levels of language. CONCLUSION: The late diagnosis and treatment of obstructive sleep apnea is associated with a delay in verbal skill acquisition. The professionals who work with children should be alert, as most of the phonetic sounds are acquired during ages 3-7 years, which is also the peak age for hypertrophy of the tonsils and childhood OSA. PMID- 27184508 TI - Airway reconstruction: review of an approach to the advanced-stage laryngotracheal stenosis. AB - INTRODUCTION: The management of laryngotracheal stenosis is complex and is influenced by multiple factors that can affect the ultimate outcome. Advanced lesions represent a special challenge to the treating surgeon to find the best remedying technique. OBJECTIVE: To review the efficacy of our surgical reconstructive approach in managing advanced-stage laryngotracheal stenosis treated at a tertiary medical center. METHODS: A retrospective review of all patients that underwent open laryngotracheal repair/reconstruction by the senior author between 2002 and 2014. Patients with mild/moderate stenosis (e.g. stage 1 or 2), or those who had an open reconstructive procedure prior to referral, were excluded. Patients who had only endoscopic treatment (e.g. laser, balloon dilatation) and were not subjected to an open reconstructive procedure at our institution, were not included in this study. Variables studied included patient demographics, clinical presentation, etiology of the laryngotracheal pathology, the location of stenosis, the stage of stenosis, the type of corrective or reconstructive procedure performed with the type of graft used (where applicable), the type and duration of stent used, the post-reconstruction complications, and the duration of follow-up. Outcome measures included decannulation rate, total number of reconstructive surgeries needed to achieve decannulation, and the number of post-operative endoscopies needed to reach a safe patent airway. RESULTS: Twenty five patients were included, aged 0.5 months to 45 years (mean 13.5 years, median 15 years) with 16 males and 9 females. Seventeen patients (68%) were younger than 18 years. Most patients presented with stridor, failure of decannulation, or respiratory distress. Majority had acquired etiology for their stenosis with only 24% having a congenital pathology. Thirty two reconstructive procedures were performed resulting in decannulating 24 patients (96%), with 15/17 (88%) pediatric patients and 5/8 (62.5%) adult patients requiring only a single reconstructive procedure. Cartilage grafts were mostly used in children (84% vs. 38%) and stents were mostly silicone made, followed by endotracheal tubes. The number of endoscopies required ranged from 1 to 7 (mean 3). More co-morbidities existed in young children, resulting in failure to decannulate one patient. Adult patients had more complex pathologies requiring multiple procedures to achieve decannulation, with grafting less efficacious than in younger patients. The pediatric patients had double the incidence of granulation tissue compared to adults. The decannulated patients remained asymptomatic at a mean follow-up of 50.5 months. CONCLUSION: The review of our approach to open airway repair/reconstruction showed its efficacy in advanced-stage laryngotracheal stenosis. Good knowledge of a variety of reconstructive techniques is important to achieve good results in a variety of age groups. PMID- 27184509 TI - Comparison of microRNA profiles between benign and malignant salivary gland tumors in tissue, blood and saliva samples: a prospective, case-control study. AB - INTRODUCTION: Salivary gland tumors (SGTs) are rare head and neck malignancies consisting of a spectrum of tumors with different biological behaviors. OBJECTIVE: In this study we aimed to find out differential expression of microRNA profiles between benign and malignant SGTs. METHODS: We investigated the possible role of 95 microRNAs in the 20 patients with salivary gland tumors with comparison of 17 patients without malignancy or salivary gland diseases. Sixteen of the tumors were benign (seven pleomorphic adenomas, nine Warthin tumors), four of them were malignant (two squamous cell carcinomas, one high grade mucoepidermoid carcinoma, one adenocarcinoma). Serum and saliva samples were collected from both patients and control group. Tissue samples of tumor masses were also collected from patient group. RESULTS: Among studied microRNAs miR-21, miR-23a, miR-27a, miR-223, miR-125b, miR-126, miR-146a, miR-30e were down regulated in the benign group compared to control group in the serum samples (p values are 0.04, 0.00005, 0.00005, 0.0022, 0.031, 0.00008, 0.044, and 0.0007, respectively). When tissue samples were studied miR-21, miR-31, miR-199a-5p, miR 146b, miR-345 were up-regulated in the malignant group compared to benign group (p values are 0.006, 0.02, 0.013, 0.013, 0.041, respectively). miR-30e showed statistically significant up-regulation in malignant tumor group's plasma samples compared to benign group (p=0.034). There was no statistically significant difference in saliva samples between groups. CONCLUSION: Our results showed that different microRNAs may play role in salivary tumor pathogenesis according to biological behavior. Although there was no difference in saliva samples between groups, according to tissue and serum samples miR-21 and 30e may have an important role; since they were down-regulated in benign tumors whereas up regulated in malignant ones. PMID- 27184510 TI - [Cardiac dysfunction secondary to an adrenergic storm or cardiomyopathy of stress among child victims of traumatism]. AB - OBJECTIVE: To provide information specific to a catecholaminergic storm during a violent stress in children. PATIENTS AND METHODS: Two clinical observations in children who suffered violent trauma. RESULTS: FIRST CASE: a boy aged 12 years victim of a drowning in Stage 3 admitted to the pediatric intensive care 02.08.2015. He was intubated, ventilated, sedated with benzodiazepines and morphine. Cardiac exploration revealed a global hypokinesis with septal dyskinesia, a 45% FES offset a slight excess of ST, a troponin I to 31.46pg/mL NT proBNB to 1291pg/mL. Dobutamine was set initially at 7 then 10 gamma/kg/min. The outcome was favorable on the heart level with improved SEF in 1 week. SECOND CASE: 13-year-old girl, victim of complete hanging, admitted on 06/08/2015 for a post-anoxic encephalopathy. Intubated, ventilated and sedated with morphine and benzodiazepines. Cardiac exploration showed septal hypokinesia with a 35% FES, a lengthening of the QT interval on the ECG, a troponin I in ultra 1.27MUg/L, NT proBNB to 215pg/mL. The child was put up 15 gamma dobutamine/kg/min. The evolution was marked by improved heart function without disturbance wall motion after 7 days. CONCLUSION: Our 2 clinical cases following accidental trauma violating represent observations of a picture simulating a syndrome of Tako-Tsubo without anginal pain objectified as our 2 patients were sedated and ultrasound abnormalities returned to normal in less than a week. PMID- 27184511 TI - Retinal arteriolar remodeling evaluated with adaptive optics camera: Relationship with blood pressure levels. AB - AIM: To research a retinal arterioles wall-to-lumen ratio or lumen diameter cut off that would discriminate hypertensive from normal subjects using adaptive optics camera. PATIENTS AND METHODS: One thousand and five hundred subjects were consecutively recruited and Adaptive Optics Camera rtx1TM (Imagine-Eyes, Orsay, France) was used to measure wall thickness, internal diameter, to calculate wall to-lumen ratio (WLR) and wall cross-sectional area of retinal arterioles. Sitting office blood pressure was measured once, just before retinal measurements and office blood pressure was defined as systolic blood pressure>=140mmHg and diastolic blood pressure>=90mmHg. ROC curves were constructed to determine cut off values for retinal parameters to diagnose office hypertension. In another population of 276 subjects office BP, retinal arterioles evaluation and home blood pressure monitoring were obtained. The applicability of retinal WLR or diameter cut-off values were compared in patients with controlled, masked, white coat and sustained hypertension. RESULTS: In 1500 patients, a WLR>0.31 discriminated office hypertensive subjects with a 0.57 sensitivity and 0.71 specificity. Lumen diameter<78.2MUm discriminated office hypertension with a 0.73 sensitivity and a 0.52 specificity. In the other 276 patients, WLR was higher in sustained hypertension vs normotensive patients (0.330+/-0.06 vs 0.292+/-0.05; P<0.001) and diameter was narrower in masked hypertensive vs normotensive subjects (73.0+/-11.2 vs 78.5+/-11.6MUm; P<0.005). CONCLUSION: A WLR higher than 0.31 is in favour of office arterial hypertension; a diameter under<78MUm may indicate a masked hypertension. Retinal arterioles analysis through adaptive optics camera may help the diagnosis of arterial hypertension, in particular in case of masked hypertension. PMID- 27184512 TI - [Prevalence and severity of hypertensive emergencies and outbreaks in the hospital emergency department of CHU Timone at Marseille: Follow-up in three months of hospitalized patients]. AB - GOAL: Evaluation of the prevalence and severity of hypertensive emergencies and crisis in an Emergency Service of Timone hospital in Marseille and follow-up of 3 months of hospitalized emergencies. METHODS: This study was conducted in the Emergency Department between April 1 and June 30, 2015. All patients with BP>180 and/or 110mmHg was recorded and classified in true emergencies (presence of visceral pain) and hypertensive isolated crisis. A phone follow-up patients was organized. RESULTS: During this period, 170 patients were identified: 95 (56%) hypertensive crisis and 75 (44%) hypertensive emergencies: 25 OAP (33%), 18 ischemic stroke (24%), 15 hemorrhagic stroke (20%), 9 angina (12%) and 8 different. The clinical characteristics of hypertensive emergencies are preferentially dyspnea (27%) motor deficit (36%), and chest pain (16%). The BP of hypertensive emergencies at their admission (3 measurements, oscillometric automatic device) is close to the hypertensive crisis (198.17+/-19.3 to 96.4+/ 21.2mmHg versus 191+/-31.6 to 96.12+/-21). The BP controlled after 15minutes of rest is lower for crisis compared to real emergencies (152+/-47 to 79+/-28 vs. 174+/-31 to 86+/-26). Age emergency is larger (77+/-14 vs. 67+/-17), the number of slightly larger drug (1.79 versus 1.67+/-1+/-1). Telephone follow-up was performed after an average period of three months. Ninety-nine patients were contacted by telephone: 46 patients who were admitted for hypertensive emergency patients and 53 for a push. Eighteen deaths have been recorded, including 15 among hypertensive emergencies (9 in hemorrhagic stroke, 5 for ischemic stroke, and 1 for OAP) with 5-hospital deaths within 48hours after admission and 10 within 3 months in patients hospitalized with hypertensive emergency or 33%. Seventy-seven patients out of 99 had been reviewed by their attending physicians. A questionnaire was sent by mail to patients who have not answered the phone contacts, and responses are pending. CONCLUSION: Hypertensive emergencies hospitalized in Timone Hospital represent 44% of patients hospitalized for emergency HTA. Their gravity is 1/3 since most patients die within three months warranting closer management of these fragile patients by creating a specialized consulting postemergency. PMID- 27184513 TI - [Prevalence and characteristics of metabolic syndrome among hypertensive patients in Abidjan]. AB - AIM: Assess prevalence of metabolic syndrome (MetS) in black Africans hypertensive patients. POPULATION: Prospective survey from 3rd November 2014 to 12th June 2015, at Abidjan Heart Institute. Study was carried out among patients aged 18 years old, admitted to external consultation. Oral consent was obtained. MetS was established based on the definitions of the NCEP-ATP III 2005 and the International Diabetes Federation (IDF). RESULTS: Over 1246 hypertensive patients, 404 were included in our study. The prevalence of MetS was 48.8% according to the criteria of the NCEP-ATP III 2005 and 51% according to the IDF. We noticed a female predominance (69% against 31%, P<0.001). Central obesity (49.5%) and low HDL-cholesterol (42.1%) were the factors defining the SM most predominant in our series. Low blood pressure control was higher in the presence of MetS (43.6%). The average number of antihypertensive prescribed drugs were significantly higher (2.2+/-0.8 against 2+/-0.8, P<0.001). MetS was significantly associated with obesity (BMI>=30kg/m(2) : 40.6% against 14%, P<0.001). Cardiovascular complications were observed in 54.8% of hypertensive patients in the presence of MetS. CONCLUSION: MetS is a reality in sub-Saharan Africa. Adequate preventive measures are needed to limit its progression. PMID- 27184514 TI - [The therapeutic effects of dietary krill oil (Euphausia superba) supplementation on oxidative stress and DNA damages markers in cafeteria diet-overfed rats]. AB - AIM: To evaluate the therapeutic effects of dietary krill oil supplementation in modulation of oxidative stress components and DNA oxidative damages marker in cafeteria diet-overfed-rats. MATERIAL AND METHODS: Eighteen aging male Wistar rats were divided into three groups of six each and were exposed for the ensuing 8 weeks to one of the diets: control group (TS) which was submitted to standard chow (330kcal/100g), containing 24% of proteins, 5% of lipids and 70% of carbohydrates. Cafeteria standard group (TC) exposed to cafeteria diet (420kcal/100g). The last group received a cafeteria diet enriched in oral force feeding krill oil 2% (CK). The plasma and tissues pro-oxydant status were assessed by assaying thiobarbituric acid reactive substances, hydroperoxydes, and isoprostans. The determination of DNA oxidative damages was evaluated by the measurement of the major products of DNA oxidation (8-OHdG). RESULTS: Exposure to a cafeteria diet increases the metabolic response to the radical attack and DNA oxidative damages in both plasma and key tissues involved in antioxidant defense. Krill oil supplementation in cafeteria diet relieves oxidative stress and DNA damages by lowering several lipid peroxidation components and the main marker of DNA oxidation in obese rats. PMID- 27184515 TI - Long-term self-reported exposure to occupational noise is associated with BMI defined obesity in the US general population. AB - BACKGROUND: Evidence is emerging about the risk of obesity associated with traffic noise. The present study aimed to explore the association between self reported occupational noise exposure and body mass index (BMI)-defined obesity in the US general population. METHODS: This study is based on the 2014 National Health Interview Survey. Information regarding self-reported occupational lifetime noise exposure was linked to self-reported BMI, adjusting for other covariates. RESULTS: The multivariate models yielded OR = 1.46 (95% CI: 1.27, 1.68) for obesity, and 0.97 kg/m2 (95% CI: 0.57, 1.36) higher BMI among participants exposed to high level of noise for >=15 years, in comparison to never exposed participants. Moderation analysis revealed that among those less than 55 years of age noise had significantly stronger adverse effect. Those without cancer and diabetes also experienced stronger adverse effect. CONCLUSIONS: Self-reported exposure to occupational noise was associated with increased odds of obesity and continuously measured BMI. Am. J. Ind. Med. 59:1009 1019, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27184516 TI - Prevalence and correlates of hookah use: a nationally representative sample of US adults ages 18-40 years old. AB - BACKGROUND: Hookah use may be increasing among adults in the US. Information on the prevalence and correlates of hookah use in the adult population is relatively limited. OBJECTIVES: To determine the prevalence of current (past 30-day) and lifetime use of hookah among adults ages 18-40 in the US and to investigate the socio-demographic characteristics associated with lifetime use. METHODS: Data were drawn from the Tobacco Use Supplement of the Current Population Survey data from May 2010, August 2010, and January 2011 (n = 85,545). Logistic regression was used to examine various demographic correlates of lifetime hookah use. RESULTS: Among 18-40 year olds, the past month prevalence rate of hookah use was 0.6% and the lifetime prevalence rate of hookah use was 3.9%. Being male, non Hispanic white, having higher levels of educational attainment, having never been married, not having any children, earning less than $20,000 annually, residing in the Midwest or western US, being a student, and being a cigarette smoker were associated with increased likelihood of lifetime hookah use. The prevalence of hookah use among current, cigarette smokers was 7.9%, more than double that of the general adult population. CONCLUSIONS: Hookah use is significantly more common among cigarette smokers and among various demographic subgroups among general adult population. Given the risks associated with hookah and poly-tobacco use, targeted public health efforts are recommended. Additionally, health-care providers may consider expanding screening tests to include hookah use. PMID- 27184518 TI - Measuring Down: Evaluating Digital Storytelling as a Process for Narrative Health Promotion. AB - Digital storytelling (DST) engages participants in a group-based process to create and share narrative accounts of life events. We present key evaluation findings of a 2-year, mixed-methods study that focused on effects of participating in the DST process on young Puerto Rican Latina's self-esteem, social support, empowerment, and sexual attitudes and behaviors. Quantitative results did not show significant changes in the expected outcomes. However, in our qualitative findings we identified several ways in which the DST made positive, health-bearing effects. We argue for the importance of "measuring down" to reflect the locally grounded, felt experiences of participants who engage in the process, as current quantitative scales do not "measure up" to accurately capture these effects. We end by suggesting the need to develop mixed-methods, culturally relevant, and sensitive evaluation tools that prioritize process effects as they inform intervention and health promotion. PMID- 27184517 TI - MicroRNA-27a Induces Mesangial Cell Injury by Targeting of PPARgamma, and its In Vivo Knockdown Prevents Progression of Diabetic Nephropathy. AB - MicroRNAs play important roles in the pathogenesis of diabetic nephropathy (DN). In this study, we found that high glucose upregulated miR-27a expression in cultured glomerular mesangial cells and in the kidney glomeruli of streptozotocin (STZ)-induced diabetic rats. miR-27a knockdown prevented high glucose-induced mesangial cell proliferation and also blocked the upregulation of extracellular matrix (ECM)-associated profibrotic genes. Reduction of cell proliferation and profibrotic gene expression by a miR-27a inhibitor depended upon the expression of peroxisome proliferator-activated receptor gamma (PPARgamma). Further studies showed that miR-27a negatively regulated PPARgamma expression by binding to the 3'-untranslated region of rat PPARgamma. An antisense oligonucleotide specific to miR-27a (antagomir-27a) significantly reduced renal miR-27a expression in STZ induced diabetic rats and significantly increased PPARgamma levels. Antagomir-27a also reduced kidney ECM accumulation and proteinuria in STZ-induced diabetic rats. These findings suggest that specific reduction of renal miR-27a decreases renal fibrosis, which may be explained in part by its regulation of PPARgamma, and that targeting miR-27a may represent a novel therapeutic approach for DN. PMID- 27184519 TI - Incidence of fall-related injuries in Iran: A population-based nationwide study. AB - BACKGROUND: Fall-related injuries are considered to be a leading cause of morbidity and disability worldwide. The aim of this study was to investigate the incidence of fall-related injuries and its determinants in Iran. METHODS: A cross sectional household survey of a representative sample of 15-64 years old Iranians was carried out in 2011. A three-stage cluster sampling design was used. Total of 1525 clusters were randomly selected. Six households in each cluster were randomly selected, and one member of each household was interviewed. Data on the demographics and history of fall-related injury were obtained using the previously validated and reliability tested Short Form Injury Questionnaire 7 (SFIQ7). In all, 7886 subjects responded to the survey. RESULTS: The incidence rate of all fall-related injuries was 59 (95%CI: 45-72) per 1000 person-year. The incidence rate of First Aid Fall-Related Injuries (FAFRIs) and Medical Attended Fall-Related Injuries (MAFRIs) were 30+/-5 and 28+/-12, respectively. Homes were the most common place of falls (52.5%). For all and MAFRIs, the most common activity leading to fall injury was walking (37.8% and 47.6%, respectively) whereas for FAFRIs was playing (31.9%). For all and FAFRIs, the most common description was as follows: upper limb as the injured organ (52.0% and 61.2%, respectively) and superficial wound as the most prevalent type of injury (39.0% and 61.8%, respectively). However, for MAFRIs, lower limb injuries (52.9%) and fracture (43.6%) were more pronounced. Risk factors for MAFRI were as follows: paid work activity (OR: 3.11; 95%CI: 2.07-4.67), playing (OR: 14.64; 95%CI: 6.34 33.80), walking (OR: 57.09; 95%CI: 28.95-112.59), driving (OR: 2.86; 95%CI: 1.23 6.63), and recreation activities (OR: 44.11; 95%CI: 14.04-138.54). Higher age and education were the other risk factors for MAFRI, as well as residing in rural areas. CONCLUSION: This study revealed considerable incidence of fall injuries in Iranian population especially in rural regions who need access to protective equipment. People need to be warned about the constant risk of fall even during non-avoidable activities such as walking, playing, driving and paid/unpaid working especially in older ages. Implementation of fall prevention measures, home and behavioural modifications are recommended. PMID- 27184520 TI - Effects of text-to-speech software use on the reading proficiency of high school struggling readers. AB - The literature highlights the benefits of text-to-speech (TTS) software when used as an assistive technology facilitating struggling readers' access to print. However, the effects of TTS software use, upon students' unassisted reading proficiency, have remained relatively unexplored. The researchers utilized an experimental design to investigate whether 9th grade struggling readers who use TTS software to read course materials demonstrate significant improvements in unassisted reading performance. A total of 164 students of 30 teachers in Hawaii participated in the study. Analyses of covariance results indicated that the TTS intervention had a significant, positive effect on student reading vocabulary and reading comprehension after 10 weeks of TTS software use (average 582 minutes). There are several limitations to the study; however, the current study opens up for discussions and need for further studies investigating TTS software as a viable reading intervention for adolescent struggling readers. PMID- 27184521 TI - Apathy and Its Response to Antipsychotic Review and Nonpharmacological Interventions in People With Dementia Living in Nursing Homes: WHELD, a Factorial Cluster Randomized Controlled Trial. AB - OBJECTIVES: Apathy is common, impactful, and difficult to manage in people with dementia. We evaluated the efficacy of nonpharmacological interventions, exercise, and social interaction, in combination with antipsychotic review, to reduce apathy in people with dementia living in nursing homes in a cluster randomized controlled trial (RCT). METHODS: Well-being and health for people with dementia (WHELD) program included a 2 * 2 * 2 factorial cluster RCT involving people with dementia living in 16 nursing homes in the United Kingdom. All homes received training in person-centered care, and were randomized to receive antipsychotic review, social interaction, and exercise, either alone or in combinations. Apathy was one of the secondary outcomes of the WHELD trial, and it was measured by the Neuropsychiatric Inventory-nursing home version at baseline and 9 months (n = 273). We used multilevel mixed effects linear regression models to assess the impact of the interventions on apathy. RESULTS: Prevalence of apathy was 44.0% (n = 120; 95% confidence interval [CI] 38.1%-49.9%) at baseline. Severity of apathy had significant positive correlations with dementia severity, neuropsychiatric symptoms, depressive symptoms, agitation, and the needs of the people with dementia (P < .001). Antipsychotic review reduced antipsychotic use, but it significantly increased apathy (beta = 5.37; SE = 0.91; P < .001). However, antipsychotic review in combination with either social interaction (beta = -5.84; SE = 1.15; P < .001) or exercise (beta = -7.54; SE = 0.93; P < .001) significantly reduced apathy. CONCLUSIONS: Antipsychotic review can play a significant role in improving apathy in people with dementia living in nursing homes, when combined with psychosocial interventions such as social interaction and exercise. Guidance must be adapted to reflect this subtlety in care. PMID- 27184522 TI - Animal-Assisted Interventions in Dutch Nursing Homes: A Survey. AB - OBJECTIVES: Animal-assisted interventions (AAI) have become more and more popular in nursing homes in the past decade. Various initiatives for using animals in nursing homes have been developed over the years (eg, animal visiting programs, residential companion animals, petting zoos) and, on the whole, the number of nursing homes that refuse animals on their premises has declined. In this survey, we aimed to determine how many Dutch nursing homes offer AAIs, what type of interventions are used, and with what aim. We also focus on the use of underlying health, hygiene, and (animal) safety protocols. METHODS: Using an online Dutch nursing home database, we invited all listed (457) nursing home organizations in the Netherlands (encompassing a total of 804 nursing home locations) to participate in our digital survey, powered by SurveyMonkey. The survey consisted of a total of 45 questions, divided into general questions about the use of animals in interventions; the targeted client population(s); and specific questions about goals, guidelines, and protocols. The results were analyzed with SPSS Statistics. RESULTS: In the end, 244 surveys, representing 165 organizations, were returned: 125 nursing homes used AAI in one way or another, 40 did not. Nursing homes that did not offer AAI cited allergy and hygiene concerns as the most important reasons. Most nursing homes offering AAI used visiting animals, mostly dogs (108) or rabbits (76). A smaller number of nursing homes had resident animals, either living on the ward or in a meadow outside. Almost all programs involved animal-assisted activities with a recreational purpose; none of the participating nursing homes provided animal assisted therapy with therapeutic goals. Psychogeriatric patients were most frequently invited to participate. A total of 88 nursing homes used alternatives when animals were not an option or not available. The most popular alternative was the use of stuffed animals (83) followed by FurReal Friends robotic toys (14). The sophisticated robot seal Paro was used in 7 nursing homes. A large percentage (80%) of nursing homes that worked with animals did not have AAI-specific health protocols or animal welfare and safety protocols underlying the animal activities or specific selection criteria for the selection of suitable animals. CONCLUSION: Most of the participating Dutch nursing homes offer AAI in recreational programs (animal assisted activities) for psychogeriatric clients (using visiting animals, especially dogs). Most nursing homes do not have specific AAI protocols for animal welfare, hygiene, and safety during animal activities, nor do they employ specific selection criteria for participating animals and their handlers. PMID- 27184523 TI - New Long-Term Care Policies in Latin America: The National System of Care in Uruguay. AB - BACKGROUND: Uruguay is the Latin American country with the largest share of elderly population and it has the greatest pressure for formal long-term care services in the region. For this reason, last year the government approved a law creating a National System of Care. OBJECTIVE: This article describes and analyzes the long-term care policy in the recently created National System of Care of Uruguay. METHOD: The Director of the National System of Care was asked to complete a questionnaire with a description and management of long-term care programs. This information was completed with official information and peer reviewed articles of long-term care in Uruguay. RESULTS: The National System of Care includes long-term care services. The main services are carried out through a cash-for-care system for home-based services, but in the future the benefits will expand to day centers and residential and nursing homes. CONCLUSION: The system follows international trends in terms of universality, services, and regulations dealing with care. However, the current and future financing is low, and this condition could undermine its development capacity. PMID- 27184525 TI - Heteroleptic Ir(iii) and Pt(ii) complexes based on 2-(2,4-difluorophenyl) pyridine and bisthienylethene BrLH: the influence of the metal center on structures, luminescence and photochromism. AB - Heteroleptic complexes [Ir(dfppy)2(BrL)].3CH3OH () and [Pt(dfppy)(BrL)].CH3OH () have been prepared based on the same ligands including bisthienylethene BrLH and dfppyH = (2-(2,4-difluorophenyl)-pyridine). Complexes and reveal distinct crystal structures. The BrL(-) anion uses its phenol-imidazole moiety to coordinate with an {Ir(dfppy)2}(+) unit in the former, while with a {Pt(dfppy)}(+) unit in the latter. Neighboring [Ir(dfppy)2(BrL)]/[Pt(dfppy)(BrL)] molecules are connected through extensive hydrogen bonds and aromatic stacking interactions, thus forming a supramolecular chain structure in , and a layer structure in . Upon irradiation with 380 nm light, compound shows photochromic behavior in CH2Cl2, with a color change from nearly colorless to light green. However, no photochromism was observed in compound . At room temperature, compound reveals phosphorescence with a predominant (3)MLCT character both in CH2Cl2 solution (emissions at 495 and 513 nm) and in the solid state (emission at 524 nm). Compound exhibits phosphorescence with a predominant (3)LC character in CH2Cl2 solution (emission at 508 nm), but it is almost non-luminescent in the solid state. Our experimental results demonstrate that the metal centers in and could significantly influence their structures, photochromism, and luminescence behaviors. PMID- 27184524 TI - Editorial. PMID- 27184526 TI - Nutritional strategies to cope with reduced litter weight gain and total tract digestibility in lactating sows. AB - Twelve lactating sows were used to evaluate the effects of reducing dietary crude protein (CP) (14% vs. 12%) and increasing neutral detergent fibre (NDF) levels (18% vs. 22%) on litter performance, total tract apparent digestibility and manure composition in a 4 * 4 latin square arrangement during a 36-day lactation period. Diets were isoenergetic (2.9 Mcal ME/kg) and had similar total lysine content (0.9%). In addition, a second aim was to compare a reference external marker method (Cr2 O3 ) with an internal feed marker [acid-insoluble ash (AIA)] for the calculation of apparent total tract digestibility of nutrients in lactating sows. The reduction of dietary CP level in lactating sows had no effect on either live-weight or backfat thickness or apparent total tract digestibility of nutrients. However, the piglets' average daily gain (ADG) was reduced in low dietary CP diets, which suggests that sows reduced milk production due to an underestimation of certain essential amino acid requirements (e.g. valine). The increase of dietary NDF level did not affect sow and litter performance. Nevertheless, the total tract apparent digestibility of organic matter, CP and carbohydrates was reduced, and ether extract digestion was increased in high NDF compared to normal NDF diets equally balanced for ME and lysine content. The coefficients of total tract apparent digestibility of nutrients in lactating sows were greater when using AIA compared to Cr2 O3 marker, regardless of dietary CP or NDF level, but their coefficients of variation were lower in the former than in the latter. In lactating sows, a trade-off between litter performance and nutrient digestion is established when reducing dietary CP or increasing NDF levels while maintaining similar lysine content through synthetic amino acids and balancing metabolizable energy through dietary fat sources. PMID- 27184527 TI - Re: Risk Assessment to Guide Cervical Screening Strategies in a Large Chinese Population (doi: 10.1002/ijc.30012). PMID- 27184528 TI - Multimodality Image-Guided Sclerotherapy of Low-Flow Orbital Vascular Malformations: Report of Single-Center Experience. AB - PURPOSE: To evaluate the role of multimodality imaging tools for intraprocedural guidance and outcome evaluation during sclerotherapy of low-flow orbital vascular malformations. MATERIALS AND METHODS: A retrospective review was performed of 17 consecutive patients with low-flow orbital malformations (14 lymphatic, two venous, and one venolymphatic) who underwent multimodality image-guided sclerotherapy between November 2012 and May 2015. Sclerotherapy technique, image guidance tools, and complications were recorded. Sclerotherapy outcome was evaluated using clinical response, magnetic resonance (MR) image-based lesion volumetry, and proptosis quantification. RESULTS: There were 22 sclerotherapy sessions performed. Intraprocedural ultrasound (US), fluoroscopy, cone-beam computed tomography (CT) and MR image fusion were used for image guidance with 100% technical success. Resolution of presenting symptoms was observed in all patients at 1-month follow-up. Four major sclerotherapy complications were successfully managed. Statistically significant reduction in lesion volume (P = .001) and proptosis (P = .0117) by MR image analysis was achieved in all patients in whom 3-month follow-up MR imaging was available (n = 13/17). There was no lesion recurrence at a median follow-up of 18 months (range, 8-38 mo). CONCLUSIONS: Multimodality imaging tools, including US, fluoroscopy, cone-beam CT, and MR fusion, during sclerotherapy of low-flow orbital malformations provide intraprocedural guidance and quantitative image-based evaluation of treatment outcome. PMID- 27184530 TI - Three-dimensional ghost imaging lidar via sparsity constraint. AB - Three-dimensional (3D) remote imaging attracts increasing attentions in capturing a target's characteristics. Although great progress for 3D remote imaging has been made with methods such as scanning imaging lidar and pulsed floodlight illumination imaging lidar, either the detection range or application mode are limited by present methods. Ghost imaging via sparsity constraint (GISC), enables the reconstruction of a two-dimensional N-pixel image from much fewer than N measurements. By GISC technique and the depth information of targets captured with time-resolved measurements, we report a 3D GISC lidar system and experimentally show that a 3D scene at about 1.0 km range can be stably reconstructed with global measurements even below the Nyquist limit. Compared with existing 3D optical imaging methods, 3D GISC has the capability of both high efficiency in information extraction and high sensitivity in detection. This approach can be generalized in nonvisible wavebands and applied to other 3D imaging areas. PMID- 27184529 TI - Histone deacetylase inhibition regulates miR-449a levels in skeletal muscle cells. AB - microRNAs (miRNAs) are small non-coding RNAs that regulate cellular processes by fine-tuning the levels of their target mRNAs. However, the regulatory elements determining cellular miRNA levels are not well studied. Previously, we had described an altered miRNA signature in the skeletal muscle of db/db mice. Here, we sought to explore the role of epigenetic mechanisms in altering these miRNAs. We show that histone deacetylase (HDAC) protein levels and activity are upregulated in the skeletal muscle of diabetic mice. In C2C12 cells, HDAC inhibition using suberoylanilide hydroxamic acid (SAHA) altered the levels of 24 miRNAs: 15 were downregulated and 9 were upregulated. miR-449a, an intronic miRNA localized within the Cdc20b gene, while being downregulated in the skeletal muscle of diabetic mice, was the most highly upregulated during HDAC inhibition. The host gene, Cdc20b, was also significantly upregulated during HDAC inhibition. Bioinformatics analyses identified a common promoter for both Cdc20b and miR-449a that harbors significant histone acetylation marks, suggesting the possibility of regulation by histone acetylation-deacetylation. These observations suggest an inverse correlation between miR-449a levels and HDAC activity, in both SAHA treated skeletal muscle cells and db/db mice skeletal muscle. Further, in SAHA treated C2C12 cells, we observed augmented occupancy of acetylated histones on the Cdc20b/miR-449a promoter, which possibly promotes their upregulation. In vivo injection of SAHA to db/db mice significantly restored skeletal muscle miR-449a levels. Our results provide insights into the potential regulatory role of epigenetic histone acetylation of the miR-449a promoter that may regulate its expression in the diabetic skeletal muscle. PMID- 27184531 TI - Electroencephalogram variability in patients with cirrhosis associates with the presence and severity of hepatic encephalopathy. AB - BACKGROUND & AIMS: The outputs of physiological systems fluctuate in a complex manner even under resting conditions. Decreased variability or increased regularity of these outputs is documented in several disease states. Changes are observed in the spatial and temporal configuration of the electroencephalogram (EEG) in patients with hepatic encephalopathy (HE), but there is no information on the variability of the EEG signal in this condition. The aim of this study was to measure and characterize EEG variability in patients with cirrhosis and to determine its relationship to neuropsychiatric status. METHODS: Eyes-closed, awake EEGs were obtained from 226 patients with cirrhosis, classified, using clinical and psychometric criteria, as neuropsychiatrically unimpaired (n=127) or as having minimal (n=21) or overt (n=78) HE, and from a reference population of 137 healthy controls. Analysis of EEG signal variability was undertaken using continuous wavelet transform and sample entropy. RESULTS: EEG variability was reduced in the patients with cirrhosis compared with the reference population (coefficient of variation: 21.2% [19.3-23.4] vs. 22.4% [20.8-24.5]; p<0.001). A significant association was observed between EEG variability and neuropsychiatric status; thus, variability was increased in the patients with minimal HE compared with their neuropsychiatrically unimpaired counterparts (sample entropy: 0.98 [0.87-1.14] vs. 0.83 [0.75-0.95]; p=0.02), and compared with the patients with overt HE (sample entropy: 0.98 [0.87-1.14] vs. 0.82 [0.71-1.01]; p=0.01). CONCLUSIONS: Variability of the EEG is associated with both the presence and severity of HE. This novel finding may provide new insights into the pathophysiology of HE and provide a means for monitoring patients over time. LAY SUMMARY: Decreased variability or increased regularity of physiological systems is documented in several disease states. Variability of the electroencephalogram was found to be associated with both the presence and severity of brain dysfunction in patients with chronic liver disease. PMID- 27184532 TI - Hypothermia in acute liver failure: What got lost in translation? PMID- 27184534 TI - [Catheter-related bacteremia: Evaluation of clinical outcomes as a plan to improve the quality of microbiological diagnosis]. PMID- 27184533 TI - Definition and risk factors for chronicity following acute idiosyncratic drug induced liver injury. AB - BACKGROUND & AIMS: Chronic outcome following acute idiosyncratic drug-induced liver injury (DILI) is not yet defined. This prospective, long-term follow-up study aimed to analyze time to liver enzyme resolutions to establish the best definition and risk factors of DILI chronicity. METHODS: 298 out of 850 patients in the Spanish DILI registry with no pre-existing disease affecting the liver and follow-up to resolution or ?1year were analyzed. Chronicity was defined as abnormal liver biochemistry, imaging test or histology one year after DILI recognition. RESULTS: Out of 298 patients enrolled 273 (92%) resolved ?1year from DILI recognition and 25 patients (8%) were chronic. Independent risk factors for chronicity were older age [OR: 1.06, p=0.011], dyslipidemia [OR: 4.26, p=0.04] and severe DILI [OR: 14.22, p=0.005]. Alanine aminotransferase (ALT), alkaline phosphatase (ALP) and total bilirubin (TB) median values were higher in the chronic group during follow-up. Values of ALP and TB >1.1 x upper limit of normal (xULN) and 2.8 xULN respectively, in the second month from DILI onset, were found to predict chronic DILI (p<0.001). Main drug classes involved in chronicity were statins (24%) and anti-infectives (24%). Histological examination in chronic patients demonstrated two cases with ductal lesion and seven with cirrhosis. CONCLUSIONS: One year is the best cut-off point to define chronic DILI or prolonged recovery, with risk factors being older age, dyslipidemia and severity of the acute episode. Statins are distinctly related to chronicity. ALP and TB values in the second month could help predict chronicity or very prolonged recovery. LAY SUMMARY: Drug-induced liver injury (DILI) patients who do not resolve their liver damage during the first year should be considered chronic DILI patients. Risk factors for DILI chronicity are older age, dyslipidemia and severity of the acute episode. Chronic DILI is not a very common condition; normally featuring mild liver profile abnormalities and not being an important clinical problem, with the exception of a small number of cases of early onset cirrhosis. PMID- 27184536 TI - Fibroadenoma in Axillary Supernumerary Breast in a 17-Year-Old Girl: Case Report. AB - BACKGROUND: Supernumerary breast or polymastia is a well documented anomaly of the breast, and commonly presents along the embryonic milk line extending between the axilla and groin. However, cases of polymastia have been recorded in the face, vulva, and perineum. The clinical significance of these anomalies include their susceptibility to inflammatory and malignant changes, and their association with other congenital anomalies of the urinary and cardiovascular systems. CASE: In this article we report a case of fibroadenoma that developed in the supernumerary breast of the right axilla in a 17-year-old girl. It is uncommon to find such palpable masses in young patients. Clinical and sonographic examination of both breasts revealed no abnormalities and no lymph nodes were detected in the axillae or the neck. No associated urologic or cardiovascular abnormalities were found, and the histopathological examination of the excisional biopsy samples showed a well-defined, capsulated intracanalicular type of fibroadenoma similar to that of eutopic mammary tissue. SUMMARY AND CONCLUSION: In this report, we describe a rare case of fibroadenoma in an accessory breast in a young woman. There are a fewer than 40 reports in the world about this subject, of which differential diagnoses include: cancer in axillary supernumerary breast, hidradenitis, axillary lymphadenomegaly, lipomas, anexial cutaneous neoplasia, cysts, and phylloides tumor. The combination of clinical examination, ultrasound, and cytology leads to adequate treatment, especially surgical. The diagnosis could be confused because of findings from cytology. In this case, because of the clinical and sonographic findings and multiple differential diagnosis, only the histopathological study was used to confirm the diagnosis. Despite its high sensitivity, cytology has low specificity and could create false positive results. However, atypical lesions can be seen in fibroadenomas, especially in younger patients, pregnant patients, and in patients who use hormonal contraception. Although there are a few reports, our case report is similar to current medical registers and, after surgical treatment, our patient had an excellent prognosis. PMID- 27184535 TI - Anti-Mullerian Hormone in Female Adolescent Cancer Patients Before, During, and After Completion of Therapy: A Pilot Feasibility Study. AB - STUDY OBJECTIVE: Alkylating agents are implicated in premature ovarian insufficiency. To optimize counseling regarding future ovarian function in survivors of adolescent cancer, we describe anti-Mullerian hormone (AMH) levels in female adolescents at diagnosis, during, and shortly after completion of chemotherapy. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: This was a prospective single-institution study. Participants were a mixed population of newly diagnosed postmenarchal female adolescents with malignancy. AMH was performed at diagnosis (T1), 6 months from diagnosis (T2), at end of therapy or 12 months [T3, whichever came first], 1 year after the end of therapy or 24 months from diagnosis [T4, whichever came first], and 18 months from the time of diagnosis (T5). All patients had baseline pelvic ultrasound examinations. Presence of menses and hot flashes were recorded at each time point. RESULTS: Sixteen participants with a median age at diagnosis of 14.3 years (range 12-17 years) were followed for 18.2 months (range, 14-24 months). Oncology diagnoses included leukemia, lymphoma, and sarcoma. Ten patients (62.5%) received alkylating agents with a median cumulative dose of 3041 mg/m2 (range, 2639-6478 mg/m2) of cyclophosphamide. Almost half (n = 7; 44%) experienced amenorrhea during treatment with resumption of menses in 6 of 7 patients (85%). Fifteen of 16 (94%) participants showed a decline in mean AMH levels by 6 months (T2) from diagnosis (15.8 IU/mL at T1 vs 6.5 IU/mL at T2; P = .003) and 12 of 15 (80%) showed at least some recovery of AMH (mean AMH at T4 = 13.2 IU/mL compared with 6.5 IU/mL at T2; P = .02). There was no difference in the mean decline nor recovery of AMH in those who did, vs did not receive cyclophosphamide. CONCLUSION: To our knowledge, this is the largest series to date in adolescents showing that AMH is uniformly suppressed during cancer therapy and short-term recovery occurs in just more than half of the patients by 18-24 months. The contribution of short-term AMH measurements in predicting long-term ovarian function remains to be defined. Long-term follow-up with serial AMH levels is required to help predict those at risk for premature ovarian insufficiency. PMID- 27184537 TI - Genital Findings in Cases of Child Sexual Abuse: Genital vs Vaginal Penetration. AB - STUDY OBJECTIVE: To (1) examine the prevalence of abnormal genital findings in a large cohort of female children presenting with concerns of sexual abuse; and (2) explore how children use language when describing genital contact and genital anatomy. DESIGN: In this prospective study we documented medical histories and genital findings in all children who met inclusion criteria. Findings were categorized as normal, indeterminate, and diagnostic of trauma. Logistic regression analysis was used to determine the effects of key covariates on predicting diagnostic findings. Children older than 4 years of age were asked questions related to genital anatomy to assess their use of language. SETTING: A regional, university-affiliated sexual abuse clinic. PARTICIPANTS: Female children (N = 1500) aged from birth to 17 years (inclusive) who received an anogenital examination with digital images. INTERVENTIONS AND MAIN OUTCOME MEASURES: Physical exam findings, medical history, and the child's use of language were recorded. RESULTS: Physical findings were determined in 99% (n = 1491) of patients. Diagnostic findings were present in 7% (99 of 1491). After adjusting for age, acuity, and type of sexual contact reported by the adult, the estimated odds of diagnostic findings were 12.5 times higher for children reporting genital penetration compared with those who reported only contact (95% confidence interval, 3.46-45.34). Finally, children used the word "inside" to describe contact other than penetration of the vaginal canal (ie, labial penetration). CONCLUSION: A history of penetration by the child was the primary predictor of diagnostic findings. Interpretation of children's use of "inside" might explain the low prevalence of diagnostic findings and warrants further study. PMID- 27184540 TI - Oxidation of SO2 to SO3 by Cerium Oxide Cluster Cations Ce2O4(+) and Ce3O6(.). AB - Cerium oxide cationic clusters (CeO2)1-3(+) were generated through laser ablation and then reacted with sulfur dioxide (SO2) at ambient conditions in an ion trap reactor and those reactions were studied and characterized by combining the art of time-of-flight mass spectrometry (TOF-MS) with density functional theory (DFT) calculations. Molecule association and oxygen atom transfer (OAT) were observed for the CeO2(+) and (CeO2)2,3(+) reaction systems, respectively. The mechanistic analysis indicates that the weak Ce-O bond strength associated with the oxygen release capacity of cerium oxide clusters is considered as the key factor to achieve the oxidation of SO2. To our best knowledge, this research should be the first example to identify the OAT reactivity of metal oxide cluster ions toward sulfur dioxide under thermal collision conditions, and a fundamental understanding of the elementary oxidation of SO2 to SO3 is provided. PMID- 27184539 TI - An Organometallic Compound which Exhibits a DNA Topology-Dependent One-Stranded Intercalation Mode. AB - Understanding how small molecules interact with DNA is essential since it underlies a multitude of pathological conditions and therapeutic interventions. Many different intercalator compounds have been studied because of their activity as mutagens or drugs, but little is known regarding their interaction with nucleosomes, the protein-packaged form of DNA in cells. Here, using crystallographic methods and molecular dynamics simulations, we discovered that adducts formed by [(eta(6) -THA)Ru(ethylenediamine)Cl][PF6 ] (THA=5,8,9,10 tetrahydroanthracene; RAED-THA-Cl[PF6 ]) in the nucleosome comprise a novel one stranded intercalation and DNA distortion mode. Conversely, the THA group in fact remains solvent exposed and does not disrupt base stacking in RAED-THA adducts on B-form DNA. This newly observed DNA binding mode and topology dependence may actually be prevalent and should be considered when studying covalently binding intercalating compounds. PMID- 27184538 TI - Low-dose lipopolysaccharide (LPS) inhibits aggressive and augments depressive behaviours in a chronic mild stress model in mice. AB - BACKGROUND: Aggression, hyperactivity, impulsivity, helplessness and anhedonia are all signs of depressive-like disorders in humans and are often reported to be present in animal models of depression induced by stress or by inflammatory challenges. However, chronic mild stress (CMS) and clinically silent inflammation, during the recovery period after an infection, for example, are often coincident, but comparison of the behavioural and molecular changes that underpin CMS vs a mild inflammatory challenge and impact of the combined challenge is largely unexplored. Here, we examined whether stress-induced behavioural and molecular responses are analogous to lipopolysaccharide (LPS) induced behavioural and molecular effects and whether their combination is adaptive or maladaptive. METHODS: Changes in measures of hedonic sensitivity, helplessness, aggression, impulsivity and CNS and systemic cytokine and 5-HT system-related gene expression were investigated in C57BL/6J male mice exposed to chronic stress alone, low-dose LPS alone or a combination of LPS and stress. RESULTS: When combined with a low dose of LPS, chronic stress resulted in an enhanced depressive-like phenotype but significantly reduced manifestations of aggression and hyperactivity. At the molecular level, LPS was a strong inducer of TNFalpha, IL-1beta and region-specific 5-HT2A mRNA expression in the brain. There was also increased serum corticosterone as well as increased TNFalpha expression in the liver. Stress did not induce comparable levels of cytokine expression to an LPS challenge, but the combination of stress with LPS reduced the stress induced changes in 5-HT genes and the LPS-induced elevated IL-1beta levels. CONCLUSIONS: It is evident that when administered independently, both stress and LPS challenges induced distinct molecular and behavioural changes. However, at a time when LPS alone does not induce any overt behavioural changes per se, the combination with stress exacerbates depressive and inhibits aggressive behaviours. PMID- 27184542 TI - Does Pure Platelet-Rich Plasma Affect Postoperative Clinical Outcomes After Arthroscopic Rotator Cuff Repair? A Randomized Controlled Trial. AB - BACKGROUND: The exact role of platelet-rich plasma (PRP) in rotator cuff tendon reconstruction remains unclear. PURPOSE/HYPOTHESIS: This study investigated whether an intraoperative pure PRP injection, compared with a local anesthetic injection, improves patient-reported outcomes at 3 and 6 months after arthroscopic rotator cuff repair. The hypothesis was that pure PRP improves patient-reported outcomes (Oxford Shoulder Score [OSS]) at 3 and 6 months after surgery and has the same pain-reducing effect compared with a postoperative subacromial local anesthetic (ropivacaine) injection. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: Between January 2011 and November 2012, a total of 120 patients who underwent arthroscopic double-row repair of a supraspinatus tendon rupture were randomized to receive either pure PRP by an injection at the footprint (PRP group; n = 60) or ropivacaine injected in the subacromial region (control group; n = 60). Seventy-eight percent of patients had other concomitant tears. All patients, surgeons, and follow-up investigators were blinded. Clinical parameters and various outcome scores (Constant-Murley shoulder score; OSS; patient American Shoulder and Elbow Surgeons score; quick Disabilities of the Arm, Shoulder and Hand score; EuroQol 5 dimensions) were documented preoperatively and at 3, 6, and 24 months postoperatively. The repair integrity was assessed by magnetic resonance imaging or ultrasound at 24 months. Furthermore, a pain diary was completed within the first 10 postoperative days, and adverse events were recorded. Group outcome differences were analyzed using t tests, Fisher exact tests, and mixed models. RESULTS: The final follow-up rate was 91%. An associated tear of the subscapularis tendon was diagnosed in 23% of PRP-treated patients and 36% of control patients. Three months after surgery, the mean (+/-SD) OSS was 32.9 +/- 8.6 in PRP-treated patients and 30.7 +/- 10.0 in control patients (P = .221). No significant differences were noted for other outcome parameters as well as at 6 and 24 months postoperatively. Smoking was a significant effect modifier. Pain for both groups decreased from postoperative day 1 to 10 without any significant group difference (P = .864). Six (12.2%) and 11 (20.8%) patients were diagnosed with a recurrent supraspinatus tendon defect in the PRP and control groups, respectively (P = .295). Twenty-two (40.7%) and 18 (30.5%) PRP-treated and control patients, respectively, experienced a local adverse event within 24 months (P = .325). CONCLUSION: Patients treated with pure PRP showed no significantly improved function at 3, 6, and 24 months after arthroscopic repair compared with control patients receiving ropivacaine; however, a similar pain reduction was documented in both groups. The negative influence of smoking on the effect of pure PRP requires further investigation. REGISTRATION: NCT01266226 (ClinicalTrials.gov). PMID- 27184541 TI - Influence of Playing a Prolonged Tennis Match on Shoulder Internal Range of Motion. AB - BACKGROUND: Shoulder range of motion (ROM) deficits have been identified as an injury risk factor among tennis players. It is well known that shoulder internal rotation deficit increases with age and years of play, but there is a lack of knowledge regarding the influence of a prolonged tennis match on shoulder ROM. PURPOSE: To examine changes in shoulder ROM during a prolonged tennis match. STUDY DESIGN: Descriptive laboratory study. METHODS: Shoulder passive internal and external rotation ROM were measured on 8 male tennis players before, every 30 minutes during, and just after a 3-hour tennis match. Total ROM was calculated as the combination of shoulder internal and external rotations. Ball velocity on the serve was measured with a radar gun before, at midmatch, and just after the match. RESULTS: Decreases in shoulder internal rotation (-20.8 degrees ; P = .005), total ROM (-24.6 degrees ; P = .001), and serve velocity (-1.8 m/s; P = .002) were observed at the end of the match. No statistically significant difference was observed for shoulder external rotation after the match (P = .460). CONCLUSION: Passive shoulder internal rotation and total ROM are significantly decreased during a 3-hour tennis match. CLINICAL RELEVANCE: The results show that a prolonged tennis match play can modify values of shoulder ROM. PMID- 27184543 TI - Hamstring Reinjuries Occur at the Same Location and Early After Return to Sport: A Descriptive Study of MRI-Confirmed Reinjuries. AB - BACKGROUND: Despite relatively high reinjury rates after acute hamstring injuries, there is a lack of detailed knowledge about where and when hamstring reinjuries occur, and studies including imaging-confirmed reinjuries are scarce. PURPOSE: To investigate the location, radiological severity, and timing of reinjuries on magnetic resonance imaging (MRI) compared with the index injury. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A MRI scan was obtained <=5 days after an acute hamstring index injury in 180 athletes, and time to return to sport (RTS) was registered. Athletes with an MRI-confirmed reinjury in the same leg <=365 days after RTS were included. Categorical grading and standardized MRI parameters of the index injury and reinjury were scored by a single radiologist (with excellent intraobserver reliability). To determine the location of the reinjury, axial and coronal views of the index injury and reinjury were directly compared on proton density-weighted fat-suppressed images. RESULTS: In the 19 athletes included with reinjury, 79% of these reinjuries occurred in the same location within the muscle as the index injury. The median time to RTS after the index injury was 19 days (range, 5-37 days; interquartile range [IQR], 15 days). The median time between the index injury and reinjury was 60 days (range, 20-316 days; IQR, 131 days) and the median time between RTS after the index injury and the reinjury was 24 days (range, 4-311 days; IQR, 140 days). More than 50% of reinjuries occurred within 25 days (4 weeks) after RTS from the index injury and 50% occurred within 50 days after the index injury. All reinjuries with more severe radiological grading occurred in the same location as the index injury. CONCLUSION: The majority of the hamstring reinjuries occurred in the same location as the index injury, early after RTS and with a radiologically greater extent, suggesting incomplete biological and/or functional healing of the index injury. Specific exercise programs focusing on reinjury prevention initiated after RTS from the index injury are highly recommended. PMID- 27184545 TI - Effects of sub-lethal concentrations of mupirocin on global transcription in Staphylococcus aureus 8325-4 and a model for the escape from inhibition. AB - Staphylococcus aureus is a major pathogen in both hospital and community settings, causing infections ranging from mild skin and wound infections to life threatening systemic illness. Gene expression changes due to the stringent response have been studied in S. aureus using lethal concentrations of mupirocin, but no studies have investigated the effects of sub-lethal concentrations. S. aureus 8325-4 was exposed to sub-inhibitory concentrations of mupirocin. The production of ppGpp was assessed via HPLC and the effects on global transcription were studied by RNAseq (RNA sequencing) analysis. Growth inhibition had occurred after 1 h of treatment and metabolic analysis revealed that the stringent response alarmone ppGpp was present and GTP concentrations decreased. Transcriptome profiles showed that global transcriptional alterations were similar to those for S. aureus after treatment with lethal concentrations of mupirocin, including the repression of genes involved in transcription, translation and replication machineries. Furthermore, up-regulation of genes involved in stress responses, and amino acid biosynthesis and transport, as well as some virulence factor genes, was observed. However, ppGpp was not detectable after 12 or 24 h and cell growth had resumed, although some transcriptional changes remained. Sub-lethal concentrations of mupirocin induce the stringent response, but cells adapt and resume growth once ppGpp levels decrease. PMID- 27184546 TI - Near Room-Temperature Memory Devices Based on Hybrid Spin-Crossover@SiO2 Nanoparticles Coupled to Single-Layer Graphene Nanoelectrodes. AB - The charge transport properties of SCO [Fe(Htrz)2 (trz)](BF4 ) NPs covered with a silica shell placed in between single-layer graphene electrodes are reported. A reproducible thermal hysteresis loop in the conductance above room-temperature is evidenced. This bistability combined with the versatility of graphene represents a promising scenario for a variety of technological applications but also for future sophisticated fundamental studies. PMID- 27184544 TI - Harmful Effects of Leukocyte-Rich Platelet-Rich Plasma on Rabbit Tendon Stem Cells In Vitro. AB - BACKGROUND: Platelet-rich plasma (PRP) is now widely used as a promising treatment for patients with tendinopathy. However, the efficacy of PRP treatment for tendinopathy is controversial mainly because of inconsistent results from human clinical trials and particularly because the concentration and effect of leukocytes in PRP remain largely unknown. HYPOTHESIS: Leukocyte-rich PRP (L-PRP) inhibits growth factor release, decreases proliferation, and induces nontenocyte differentiation of tendon stem cells (TSCs); increases catabolic cytokine concentrations; and causes inflammation and apoptosis. Thus, L-PRP has a detrimental effect on tendon stem/progenitor cells, which impairs injured tendon healing. STUDY DESIGN: Controlled laboratory study. METHODS: Pure PRP (P-PRP) and L-PRP were prepared from the same individual rabbit blood, and platelet numbers in each PRP product were adjusted to reach the same level. The leukocyte level in L-PRP was 4 and 8 times higher than those in whole blood and P-PRP, respectively. The growth factors in both P-PRP and L-PRP were measured by enzyme-linked immunosorbent assay kits. The morphology, stemness, proliferation, and differentiation of TSCs grown in L-PRP and P-PRP were examined by microscopy, immunocytochemistry, population doubling time, quantitative real-time polymerase chain reaction, and histological analysis. RESULTS: L-PRP produced lower levels of growth factors, such as vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), transforming growth factor (TGF)-beta1, and platelet-derived growth factor (PDGF), than did P-PRP. TSC proliferation was significantly decreased in L-PRP in a concentration-dependent manner. Furthermore, TSCs cultured in P-PRP produced more collagen and formed tendon-like tissue; however, TSCs grown in L-PRP differentiated into nontenocytes and produced more inflammatory factors such as membrane-associated prostaglandin synthase (mPGES) and interleukin (IL)-1beta. Moreover, L-PRP was associated with increased apoptosis. CONCLUSION: L-PRP has harmful effects on TSCs. CLINICAL RELEVANCE: This study revealed the direct effects of different compositions of PRP on TSCs and provided basic scientific data to help understand the cellular and molecular mechanisms of the efficacy of PRP treatment in clinical use. PMID- 27184547 TI - Men becoming fathers by intracytoplasmic sperm injection were more often born small for gestational age. AB - Being born with nonoptimal birth characteristics decreases the chance of becoming a father. Urogenital malformations as well as metabolic syndrome are more common in men born small for gestational age (SGA) and could be contributing factors to the reduced fertility rate seen in these men. It could imply that men becoming fathers by assisted reproductive technology (ART) more often are born with low birth weight (LBW), preterm, and/or SGA than men conceiving without treatment and also that men where intracytoplasmic sperm injection (ICSI) had to be performed more often are born with nonoptimal birth characteristics than men where conventional in vitro fertilization (IVF) successfully could be used. In this retrospective, case-control study using Swedish national registers, we compared the birth characteristics of 1206 men who have become fathers by ART with a control group consisting of age-matched men who became fathers without treatment. The differences in birth characteristics between men becoming fathers by IVF and ICSI were also assessed. For men becoming fathers by ART, OR of being born with LBW was 1.66 (95% CI = 1.17-2.36) compared with fathers who conceived without treatment. OR of being born prematurely was 1.32 (95% CI = 1.00-1.77). Men becoming fathers via ICSI had a doubled increased likelihood of being born SGA compared with men who became fathers via IVF (OR = 2.12; 95% CI = 1.17-3.83). In conclusion, we have found that men becoming fathers by ICSI treatments had more often been born SGA than men becoming fathers by conventional IVF. PMID- 27184548 TI - Personalized prostate cancer care: from screening to treatment. AB - Unprecedented progress has been made in genomic personalized medicine in the last several years, allowing for more individualized healthcare assessments and recommendations than ever before. However, most of this progress in prostate cancer (PCa) care has focused on developing and selecting therapies for late stage disease. To address this issue of limited focus, we propose a model for incorporating genomic-based personalized medicine into all levels of PCa care, from prevention and screening to diagnosis, and ultimately to the treatment of both early-stage and late-stage cancers. We have termed this strategy the "Pyramid Model" of personalized cancer care. In this perspective paper, our objective is to demonstrate the potential application of the Pyramid Model to PCa care. This proactive and comprehensive personalized cancer care approach has the potential to achieve three important medical goals: reducing mortality, improving quality of life and decreasing both individual and societal healthcare costs. PMID- 27184549 TI - The burden of prostatic calculi is more important than the presence. AB - Prostatic calculi are a common finding on transrectal prostate ultrasound. However, it remains unclear whether they are significantly associated with lower urinary tract symptoms (LUTS). Our objective was to evaluate the association between prostatic calculi and LUTS with a focus on "calculi burden" because no studies have investigated prostatic calculi using "calculi burden" as an indicator. A total of 606 participants who received transrectal prostate ultrasound were divided into two groups according to the presence of prostatic calculi. "Calculi burden" was defined as the sum of the transverse diameters of all visible calculi within the prostate. The International Prostatic Symptom Score (IPSS) and a quality of life (QoL) score were collected. Both groups were compared, and a multivariate analysis was performed to predict moderate/severe LUTS. Linear correlation was evaluated between calculi burden and IPSS in the calculi group. No differences in total IPSS, voiding IPSS, or QoL score were detected between the two groups, but storage IPSS was significantly higher in the calculi group than that of controls. The multivariate analysis showed that the presence of prostatic calculi was not an independent predictor of moderate/severe LUTS. A positive linear correlation was detected between calculi burden and storage IPSS in calculi group (r = 0.148). However, no correlation was found between calculi burden and total IPSS, voiding IPSS, or QoL score. Our results showed that the presence of prostatic calculi was not a significant factor predicting moderate/severe LUTS. However, an increased calculi burden may be associated with aggravating storage symptoms. PMID- 27184550 TI - Ecdysis period of Rhodnius prolixus head investigated using phase contrast synchrotron microtomography. AB - Microtomography using synchrotron sources is a useful tool in biological imaging research since the phase coherence of synchrotron beams can be exploited to obtain images with high contrast resolution. This work is part of a series of works using phase contrast synchrotron microtomography in the study of Rhodnius prolixus head, the insect vector of Chagas' disease, responsible for about 12,000 deaths per year. The control of insect vector is the most efficient method to prevent this disease and studies have shown that the use of triflumuron, a chitin synthesis inhibitor, disrupted chitin synthesis during larval development and it's an alternative method against insect pests. The aim of this work was to investigate the biological effects of treatments with triflumuron in the ecdysis period (the moulting of the R. prolixus cuticle) using the new imaging beamline IMX at LNLS (Brazilian Synchrotron Light Laboratory). Nymphs of R. prolixus were taken from the Laboratory of Biochemistry and Physiology of Insects, Oswaldo Cruz Foundation, Brazil. Doses of 0.05mg of triflumuron were applied directly to the abdomen on half of the insects immediately after feeding. The insects were sacrificed 25days after feeding (intermoulting period) and fixed with glutaraldehyde. The results obtained using phase contrast synchrotron microtomography in R. prolixus showed amazing images of the effects of triflumuron on insects in the ecdysis period, and the formation of the new cuticle on those which were not treated with triflumuron. Both formation and malformation of this insect's cuticle have never been seen before with this technique. PMID- 27184551 TI - Dosimetric impact of 4DCT artifact in carbon-ion scanning beam treatment: Worst case analysis in lung and liver treatments. AB - INTRODUCTION: We evaluated the impact of 4DCT artifacts on carbon-ion pencil beam scanning dose distributions in lung and liver treatment. METHODS & MATERIALS: 4DCT was performed in 20 liver and lung patients using area-detector CT (original 4DCT). 4DCT acquisition by multi-detector row CT was simulated using original 4DCT by selecting other phases randomly (plus/minus 20% phases). Since tumor position can move over the respiratory range in original 4DCT, mid-exhalation was set as reference phase. Total prescribed dose of 60Gy (RBE) was delivered to the clinical target volume (CTV). Reference dose distribution was calculated with the original CT, and actual dose distributions were calculated with treatment planning parameters optimized using the simulated CT (simulated dose). Dose distribution was calculated by substituting these parameters into the original CT. RESULTS: For liver cases, CTV-D95 and CTV-Dmin values for the reference dose were 97.6+/-0.5% and 89.8+/-0.6% of prescribed dose, respectively. Values for the simulated dose were significantly degraded, to 88.6+/-14.0% and 46.3+/-26.7%, respectively. Dose assessment results for lung cases were 84.8+/-12.8% and 58.0+/ 24.5% for the simulated dose, showing significant degradation over the reference dose of 95.1+/-1.5% and 87.0+/-2.2%, respectively. CONCLUSIONS: 4DCT image quality should be closely checked to minimize degradation of dose conformation due to 4DCT artifacts. Medical staff should pay particular attention to checking the quality of 4DCT images as a function of respiratory phase, because it is difficult to recognize 4DCT artifact on a single phase in some cases. PMID- 27184554 TI - McKittrick-Wheelock syndrome: A rare cause of metabolic coma. PMID- 27184552 TI - Childhood diarrhea in high and low hotspot districts of Amhara Region, northwest Ethiopia: a multilevel modeling. AB - BACKGROUND: Childhood diarrhea is one of the major public health problems in Ethiopia. Multiple factors at different levels contribute to the occurrence of childhood diarrhea. The objective of the study was to identify the factors affecting childhood diarrhea at individual and community level. METHODS: A cross sectional study design was employed from February to March 2015 in high and low hotspot districts of Awi and West and East Gojjam zones in Amhara Region, northwest Ethiopia. Districts with high and low hotspots with childhood diarrhea were identified using SaTScan spatial statistical analysis. A total of 2495 households from ten (five high and five low hotspot) randomly selected districts were included in the study. A semi-structured questionnaire was used to collect data. Data were entered and cleaned in Epi Info 3.5.2 version and analyzed using Stata version 12. A multilevel logistic regression was used to identify factors associated with childhood diarrhea. RESULTS: The prevalence of childhood diarrhea was 13.5 % and did not show significant variation between high [14.3 % (95 % CI 12.3-16.2 %)] and low [12.7 % (95 % CI 10.9-14.6 %)] hotspot districts. Individual- and community-level factors accounted for 35 % of childhood diarrhea variation across the communities in the full model. Age of children (6-35 months), complementary feeding initiation below 6 months, inadequate hand washing practices, limited knowledge of mothers on diarrhea, lowest wealth status of households, and longer time interval to visit households by health extension workers were factors for increasing the odds of childhood diarrhea at the individual level. At the community level, lack of improved water supply and sanitation and unvaccinated children with measles and rotavirus vaccine were the factors associated with childhood diarrhea. CONCLUSIONS: In this study, childhood diarrhea occurrences remained high. Both individual- and community-level factors determined the occurrence of diarrhea. Interventions should consider both individual- and community-level factors to reduce the occurrence of childhood diarrhea. PMID- 27184553 TI - Foot drop during adalimumab therapy for Crohn disease. PMID- 27184556 TI - Unexpected Gifts. PMID- 27184555 TI - Endoscopic diverticulotomy using LigasureTM. AB - INTRODUCTION: Endoscopic treatment of Zenker diverticulum is considered feasible, effective and safe. The use of the LigasureTM vessel sealer provides adequate and quick dissection of tissue, achieving effective haemostasis. PATIENTS AND METHODS: Retrospective, descriptive study of all patients with Zenker diverticulum who were treated by endoscopic diverticulotomy using LigasureTM. The procedure was performed in the endoscopy unit under deep sedation controlled by the endoscopist. Patients were subsequently admitted for observation and, after discharge, were followed-up in the outpatient clinic. RESULTS: Eight patients, 5 women and 3 men, mean age 78+/-15 years, 25% ASA I, 36% ASA II, 14% ASA III and 25% ASA IV. Main symptom: dysphagia. Diverticula size: 1-7cm. Technical success: 100%. COMPLICATIONS: one patient with upper gastrointestinal bleeding. Average stay: 24h. Seven patients: asymptomatic; one patient with partial improvement, requiring repeat endoscopic intervention. Surgery and morbidity and mortality: 0%. CONCLUSION: The treatment of Zenker diverticulum by endoscopic diverticulotomy using the LigasureTM vessel sealer is highly effective, fast and safe, and could be considered the treatment of choice. PMID- 27184558 TI - Comment on: "sagittal MRI often overestimates the degree of cerebellar tonsillar ectopia: a potential for misdiagnosis of the Chiari I malformation", by R. Shane Tubbs et al. PMID- 27184557 TI - A highly sensitive and facile graphene oxide-based nucleic acid probe: Label-free detection of telomerase activity in cancer patient's urine using AIEgens. AB - Molecular beacon (MB)-based sensing platforms that consist of a fluorogen quencher pair play an important role in medical and biological researches. However, the synthesis of both fluorogen and quencher in the nucleic acid probes will increase the burden of organic synthesis works and induce the difficulties for precisely controlling the relative distance between fluorogen and quencher, which may lead to false-positive and false-negative results. In this work, initially we report a single labeled MB (FAM-MB, with carboxyfluorescein as fluorogen and without quencher) thus simplifies MBs with the aid of graphene oxide (GO) to detect telomerase activity. To further simplify this structure, namely label-free strategy, we design a facile, sensitive and selective platform using a label-free beacon (AIE-MB, without fluorogen and quencher), based on aggregation-induced emission fluorogen (silole-R). Upon the addition of telomerase, AIE-MB induced comb-like DNA structure leads to high aggregation of silole-R and thus exhibits strong fluorescence emission. By exploitation of this, we can detect telomerase with superior sensitivity and demonstrate their applications in bladder cancer diagnosis. Compared to single-labeled FAM-MB based telomerase activity assay, the label-free AIE-MB induced method could perform the sensitive detection with high signal-to-background ratio. PMID- 27184559 TI - Sagittal MRI often overestimates the degree of cerebellar tonsillar ectopia: a potential for misdiagnosis of the Chiari I malformation. AB - BACKGROUND: We hypothesized that by using coronal MRI, Chiari I malformation could be more precisely diagnosed, would provide simple anatomic landmarks, would provide information regarding asymmetry of hindbrain herniation, and would be a better method for analyzing the tonsillar herniation postoperatively when the opisthion has been removed. METHODS: Fifty consecutive pediatric patients diagnosed with Chiari I malformation had comparison between the measurements of their caudally descended cerebellar tonsils on midsagittal and coronal MRI images. RESULTS: On MRI coronal imaging, tonsillar asymmetry was found in 48 patients. Maximal left tonsillar descent was 20.9 mm, and maximal right tonsillar descent was 17.4 mm. On MRI sagittal imaging, tonsillar descent ranged from 5 to 27.4 mm. Fifty-eight % of patients had syringomyelia. Five patients (10 %) on coronal MRI were found to have both cerebellar tonsils that were less than 3 mm below the foramen magnum. However, all of these patients had greater than 3 mm of tonsillar ectopia on sagittal imaging. Nineteen patients (38 %) on coronal MRI were found to have one of the cerebellar tonsils that were less than 3 mm below the foramen magnum. Similarly, each of these had greater than 3 mm of tonsillar ecotpia as measured on midsagittal MRI. Also, based on these findings, Chiari I malformation is almost always an asymmetrical tonsillar ectopia. CONCLUSIONS: Sagittal MRI overestimates the degree of tonsillar ectopia in patients with Chiari I malformation. Misdiagnosis may occur if sagittal imaging alone is used. The cerebellar tonsils are paramedian structures, and this should be kept in mind when interpreting midline sagittal MRI. PMID- 27184560 TI - Intramedullary dermoid cyst infection mimicking holocord tumor: should radical resection be mandatory?-a case report. AB - BACKGROUND: Dermoid cysts are benign lesions which contain epidermal and dermal elements. Dermoid cysts usually contain a dermal sinus tract but this is not mandatory. Dermoid cysts can manifest by spinal cord infection without a dermal sinus tract. An infected spinal dermoid cyst associated with a holocord spinal abscess poses diagnostic and surgical challenges. Although radical surgical drainage is considered as the main treatment modality for spinal abscess, less extensive surgery for microbiological sampling and appropriate antibiotic treatment can be another alternative modality. CASE DESCRIPTION: A 1-year-old boy patient was admitted to our hospital with progressive paraplegia, bladder dysfunction, and neck rigidity. Medical history of the patient included recurrent urinary tract infection and cephalosporin treatments several times. Initial neurological examination revealed confusion, fever, neck rigidity, paraplegia (also, the motor power of the right upper extremity was three fifths that of the upper extremities). He had urinary and gastrointestinal retention. Conservative surgery was performed to take pathological and microbiological samples. With appropriate antibiotic regimen, the nuchal rigidity and fever improved dramatically. Infectious parameters in blood biochemistry significantly decreased after the antibiotic regimen. DISCUSSION AND CONCLUSION: Holocord spinal abscesses are a rare entity. The source of the disease can be hemopoietic spread or contagious spread. The dermal sinus tract is major risk factor for contagious spread. The major hemopoietic sources are urogenital infection, endocarditis, and infective lung diseases. The hemopoietic spread is a more common source for pediatric patients. The thoracolumbar region is the most common site of involvement. Spinal infection has a tendency to extend longitudinally throughout spinal fibers. The pathogenesis of the holocord edema or syrinx is uncertain. The underlying etiology may be inflammation, infection, and associated venous congestion within the spinal canal. Also, CSF circulation alteration due to arachnoiditis may be another etiological factor. The most important entities on outcome are appropriate surgical treatment and antibiotic administration. PMID- 27184562 TI - Evaluation of the Role of Circulating Long Non-Coding RNA H19 as a Promising Novel Biomarker in Plasma of Patients with Gastric Cancer. AB - BACKGROUND: H19 is one of the long non-coding RNAs (LncRNA) that is related to the progression of many diseases including cancers. This work was carried out to study the level of the long non-coding RNA; H19, in plasma of patients with gastric cancer (GC) and to assess its significance in their clinical management. METHODS: Sixty-two participants were enrolled in the present study. The first group included 32 GC patients. The second group was formed of 30 age and sex matched healthy volunteers serving as a control group. Plasma samples were used to assess H19 gene expression using real-time quantitative PCR technique. RESULTS: H19 expression was up-regulated and closely related to TNM cancer stages in GC patients. Using Receiver Operating Characteristic (ROC) curve analysis, a cutoff level of 0.5 was set for H19 expression to diagnose GC cases achieving a sensitivity of 68.75%, specificity of 56.67%, positive predictive value (PPV) 62.86% and negative predictive value (NPV) 62.96% with an area under the curve (AUC) of 72.4%. Combined use of Carcinoembryonic Antigen (CEA) and H19 level in GC diagnosis was evaluated using ROC curve revealing improvement in performance with an area under the curve of 80.4%. CONCLUSIONS: Up-regulation of H19 is closely associated with gastric cancer displaying progressive up-regulation in advanced stages of the disease implementing its role as a potential non-invasive diagnostic biomarker in gastric cancer and as a novel tool in gastric cancer management with better performance achieved on using both CEA and H19 simultaneously. PMID- 27184561 TI - Detecting spatial-temporal cluster of hand foot and mouth disease in Beijing, China, 2009-2014. AB - BACKGROUND: The incidence of hand, foot, and mouth disease (HFMD) is extremely high, and has constituted a huge disease burden throughout Beijing in recent years. This study aimed to determine the spatiotemporal distribution and epidemic characteristics of HFMD. METHODS: Descriptive statistics was used to analyze the data and estimate the epidemic peaks in 2009-2014. Space-time scanning detected spatiotemporal clusters and identified high-risk locations. Global and local Moran's I statistics were used to measure the spatial autocorrelation. Geocoding was performed in ArcGIS, based on the present address codes of the patients and the centroids of the towns. Maps were created in ArcGIS to show the geographic spread of HFMD. RESULTS: In total, 220,451probable cases of HFMD were reported in Beijing between January 2009 and December 2014: 12,749 (5.78 %) were laboratory confirmed, and 35 (0.02 %) were fatal. The median age of reported cases was 3.12 years (interquartile range 1.96-4.39). Coxsackievirus A16 (CV-A16), enterovirus 71 (EV-A71), and other enteroviruses accounted for 39.31, 35.36, and 25.33 % of the 12,749 confirmed cases, respectively. Many more severe cases were caused by EV-A71 (chi (2) = 186.41, df = 1, P < 0.001) and other enteroviruses (chi (2) = 156.44, df = 1, P < 0.001) than by CV-A16. A large single distinct peak occurred between May and July each year. Spatiotemporal clusters of HFMD were identified in Beijing during 2009-2014. The most likely clusters were detected and tended to move from the southwest (Fengtai and Daxing) southeastwards to Daxing and Tongzhou in 2009-2014. The incidence of HFMD was not randomly distributed, but showed global and local spatial autocorrelations. CONCLUSIONS: There were obvious spatiotemporal clusters of HFMD in Beijing in 2009-2014. High-incidence areas mainly occurred at the junctions of urban and rural zones. More attention should be paid to the epidemiological and spatiotemporal characteristics of HFMD to establish new strategies for its control. Health issues should be especially promoted in kindergartens and at urban-rural junctions. PMID- 27184563 TI - Application of Ynamides in the Synthesis of 2-(Tosylamido)- and 2,5 Bis(tosylamido)thiophenes. AB - A step-economic and metal-catalyst-free synthesis of 2-(tosylamido)- and 2,5 bis(tosylamido)-thiophenes from nonsymmetrical 1,3-butadiynamides and symmetrical 1,3-butadiyne-1,4-diamides is reported. The reaction proceeds in the presence of Na2S.9H2O (2-3 equiv) under mild reaction conditions (50 degrees C) and is facilitated by polarized carbon-carbon triple bonds in ynamides. This new approach to thiophenes based on the chemistry of ynamides was applied to the synthesis of a bis(tosylamido)-capped terthiophene having a string of N,S heteroatoms embedded in a highly pi-conjugated molecular frame. PMID- 27184565 TI - Producing Radical-Free Hyperpolarized Perfusion Agents for In Vivo Magnetic Resonance Using Spin-Labeled Thermoresponsive Hydrogel. AB - Dissolution dynamic nuclear polarization (DNP) provides a way to tremendously improve the sensitivity of nuclear magnetic resonance experiments. Once the spins are hyperpolarized by dissolution DNP, the radicals used as polarizing agents become undesirable since their presence is an additional source of nuclear spin relaxation and their toxicity might be an issue. This study demonstrates the feasibility of preparing a hyperpolarized [1-(13) C]2-methylpropan-2-ol (tert butanol) solution free of persistent radicals by using spin-labeled thermoresponsive hydrophilic polymer networks as polarizing agents. The hyperpolarized (13) C signal can be detected for up to 5 min before the spins fully relax to their thermal equilibrium. This approach extends the applicability of spin-labeled thermoresponsive hydrogel to the dissolution DNP field and highlights its potential as polarizing agent for preparing neat slowly relaxing contrast agents. The hydrogels are especially suited to hyperpolarize deuterated alcohols which can be used for in vivo perfusion imaging. PMID- 27184566 TI - Risk Factors for Sexual Offending in Men Working With Children: A Community-Based Survey. AB - Identifying risk factors for sexual abuse in men who work with children and who have already abused a child could lead to more appropriate screening and prevention strategies and is thus of major scientific and societal relevance. A total of 8649 German men from the community were assessed in an extensive anonymous and confidential online survey. Of those, 37 (0.4 %) could be classified as child sexual abusers working with children, 90 (1.0 %) as child sexual abusers not working with children, and 816 (9.4 %) as men who work with children and who have not abused a child. We assessed the impact of working with children as an individual risk factor for self-reported child sexual abuse and compared personal factors, pedophilic sexual fantasies, deviant sexual behaviors, antisocial behaviors, and hypersexuality among the three groups. Most interestingly, working with children was significantly associated with a self reported sexual offense against children; however, it explained only three percent of its variance. Child sexual abusers working with children admitted more antisocial and more sexually deviant behaviors than child sexual abusers not working with children and than men working with children who have not abused a child. Our findings support some of the suggestions made by other researchers concerning factors that could be considered in applicants for child- or youth serving institutions. However, it has to be pointed out that the scientific basis still seems premature. PMID- 27184567 TI - Erratum to: A National Study of Lesbian, Gay, Bisexual (LGB), and Non-LGB Youth Sexual Behavior Online and In-Person. PMID- 27184564 TI - Advances in antibiotic therapy in the critically ill. AB - Infections occur frequently in critically ill patients and their management can be challenging for various reasons, including delayed diagnosis, difficulties identifying causative microorganisms, and the high prevalence of antibiotic resistant strains. In this review, we briefly discuss the importance of early infection diagnosis, before considering in more detail some of the key issues related to antibiotic management in these patients, including controversies surrounding use of combination or monotherapy, duration of therapy, and de escalation. Antibiotic pharmacodynamics and pharmacokinetics, notably volumes of distribution and clearance, can be altered by critical illness and can influence dosing regimens. Dosing decisions in different subgroups of patients, e.g., the obese, are also covered. We also briefly consider ventilator-associated pneumonia and the role of inhaled antibiotics. Finally, we mention antibiotics that are currently being developed and show promise for the future. PMID- 27184568 TI - Diagnosis of pupillary block glaucoma after removal of congenital cataracts with intraoperative ultrasound biomicroscopy: a case report. AB - BACKGROUND: Aphakic glaucoma is a common complication after congenital cataract extraction, especially in those who have surgery during infancy. This case report describes a case of bilateral pupillary block glaucoma diagnosed with intraoperative ultrasound biomicroscopy (UBM) after removal of congenital cataract. CASE PRESENTATION: We present a case report of a 9-month-old infant with bilateral corneal enlargement and ocular hypertension after uneventful removal of congenital cataracts. Initial and follow-up examination findings were reviewed. The infant was suspected to have developmental glaucoma and schemed to have bilateral trabeculotomy until pupillary obstruction by vitreous herniation and angle closure with iris bombe were detected by intraoperative UBM. Anterior vitrectomy and goniosynechialysis were then performed as treatment. CONCLUSION: Pupillary block glaucoma is a rare type of infantile aphakic glaucoma. Application of intraoperative UBM can assist in the differential diagnosis of aphakic glaucoma in infants. PMID- 27184570 TI - Addressing Inequities in Urban Health: Do Decision-Makers Have the Data They Need? Report from the Urban Health Data Special Session at International Conference on Urban Health Dhaka 2015. AB - Rapid and uncontrolled urbanisation across low and middle-income countries is leading to ever expanding numbers of urban poor, defined here as slum dwellers and the homeless. It is estimated that 828 million people are currently living in slum conditions. If governments, donors and NGOs are to respond to these growing inequities they need data that adequately represents the needs of the urban poorest as well as others across the socio-economic spectrum.We report on the findings of a special session held at the International Conference on Urban Health, Dhaka 2015. We present an overview of the need for data on urban health for planning and allocating resources to address urban inequities. Such data needs to provide information on differences between urban and rural areas nationally, between and within urban communities. We discuss the limitations of data most commonly available to national and municipality level government, donor and NGO staff. In particular we assess, with reference to the WHO's Urban HEART tool, the challenges in the design of household surveys in understanding urban health inequities.We then present two novel approaches aimed at improving the information on the health of the urban poorest. The first uses gridded population sampling techniques within the design and implementation of household surveys and the second adapts Urban HEART into a participatory approach which enables slum residents to assess indicators whilst simultaneously planning the response. We argue that if progress is to be made towards inclusive, safe, resilient and sustainable cities, as articulated in Sustainable Development Goal 11, then understanding urban health inequities is a vital pre-requisite to an effective response by governments, donors, NGOs and communities. PMID- 27184569 TI - The early childhood oral health program: a qualitative study of the perceptions of child and family health nurses in South Western Sydney, Australia. AB - BACKGROUND: Early childhood caries affects nearly half the population of Australian children aged 5 years and has the potential to negatively impact their growth and development. To address this issue, an Early Childhood Oral Health (ECOH) program, facilitated by Child and Family Health Nurses (CFHNs), commenced in 2007 in New South Wales, Australia. This study builds on the previous evaluation of the program. It aims to explore the perceptions of CFHNs regarding the implementation of the ECOH program in South Western Sydney and the challenges and barriers related to its sustainability. METHODS: A descriptive qualitative design was used in this study. Two focus groups were conducted with 22 CFHNs who were sampled from two Community Health Centres in South Western Sydney, Australia. Data were transcribed verbatim and thematic analysis was undertaken. RESULTS: Most CFHNs acknowledged the importance of early childhood oral health promotion and were providing education, oral assessments and referrals during child health checks. Many stressed the need for collaboration with other health professionals to help broaden the scope of the program. Some barriers to implementing the program included confusion regarding the correct referral process, limited feedback from dental services and the lack of oral health awareness among parents. CONCLUSION: The study findings suggest that the ECOH program is being sustained and effectively implemented into practice by CFHNs. Improvement in the referral and feedback process as well as enhancing parental knowledge of the importance of infant and child oral health could further strengthen the effectiveness of the program. Expanding oral health education opportunities into general practice is advocated, while regular on-line training for CFHNs is preferred. Future research should include strategies to reduce non attendances, and an assessment of the impact on the prevalence of childhood caries of the ECOH program. PMID- 27184571 TI - Urban Health Research in Africa: Themes and Priority Research Questions. PMID- 27184573 TI - Assessing Self-Control and Geosocial Networking App Behavior Among an Online Sample of Men Who Have Sex with Men. AB - Geosocial networking phone applications (GSN apps) used to meet sexual partners have become popular in the men who have sex with men (MSM) communities of the USA since 2009. Previous studies have shown greater incidence of gonorrhea and chlamydia and lower testing frequency for HIV testing among GSN app users when compared to non-users. The present study aims to determine the type, number, and frequency of apps used, as well as the association between dispositional self control and health-related behaviors. Participants (n = 146) were recruited from Amazon's Mechanical Turk program to respond to a brief GSN app marketing survey. Multivariate regression was used to determine differences in app priorities, length of app use, and number of sexual partners between high self-control and low self-control participants. A majority of the participants reported using Grindr (78 %) followed by Scruff (19 %), Growlr (12 %), and Jack'd (12 %). Most individuals used one app only (58 %), but a significant proportion reported using two apps (28 %) or three or more apps (14 %). Respondents with low self-control were more likely to report a higher number of hours using GSN apps and a higher number of sexual partners, controlling for race/ethnicity, education, employment, and HIV status. Given the popularity of this burgeoning communication medium, these findings have important implications for developing prevention resources for different segments of GSN app users. PMID- 27184572 TI - Role of Direct and Indirect Violence Exposure on Externalizing Behavior in Children. AB - The objective of this study was to examine the association between externalizing behaviors and indirect violence exposure, assessed both within the household and at the community level, as well as the interaction effect of indirect and direct violence exposure. A sample of parents of children ages 4-15 who have not been referred or enrolled in child welfare (n = 82) were recruited from the greater New Orleans community. Externalizing behavior was assessed with the Child Behavior Checklist (CBCL). The child's indirect exposure to violence included witnessing community violence, witnessing physical assault, and witnessing fighting or domestic violence at home. Direct exposure to violence included the child experiencing physical aggression from a caregiver. All assessments were based on caregiver reports. To decrease potential for confounding, children were matched for analysis based on age, Hurricane Katrina exposure, and their propensity to be exposed to high indirect violence. Cumulative indirect exposure to violence was significantly positively correlated with CBCL scores. After controlling for key covariates, CBCL externalizing T score increased significantly by approximately 1.25 points for each level increase in indirect violence exposure (beta = 1.25, SE = 0.57, p = 0.027). There also was a significant interaction between indirect and direct exposure to violence in the association with CBCL score (beta = -0.08, SE = 0.03, p = 0.002). These findings extend previous research by demonstrating that exposure to both direct and cross contextual indirect violence influences externalizing behaviors in children. Additionally, the findings suggest that community and household social environments are both important targets for interventions designed to decrease externalizing behaviors and improve long-term outcomes for youth at risk of exposure to violence. PMID- 27184575 TI - Implications of circulating irisin and Fabp4 levels in patients with polycystic ovary syndrome. AB - The aim of the study was to evaluate the fatty acid-binding protein-4 (FABP4) and irisin concentrations in women with polycystic ovary syndrome (PCOS). Forty-nine women with PCOS, diagnosed according to Rotterdam criteria and 39 healthy women matched for body mass index (BMI) and age. Serum irisin and plasma FABP4 concentrations were measured in both groups. The association of irisin and FABP4 concentrations with metabolic parameters were also tested. Women with PCOS had significantly lower mean serum irisin concentrations than control subjects (158.5 +/- 123.3 versus 222.9 +/- 152.2 ng/ml, p < 0.05). Concentrations of FABP4 in PCOS and control groups were not significantly different (10.5 +/- 4.4 versus 10.9 +/- 4.2 ng/ml, p > 0.05). FABP4 concentrations were correlated with BMI, waist-hip ratio (WHR) and HOMA-IR (r = 0.57, p = 0.001; r = 0.26, p = 0.03; r = 0.26, p = 0.03, respectively). No associations between irisin and all the others parameters except serum levels of LH were found. Serum irisin concentrations of women with PCOS were lower compared to the controls. Moreover, there were no difference in plasma FABP4 concentrations between women with PCOS and controls. PMID- 27184574 TI - Putative virulence factors of Corynebacterium pseudotuberculosis FRC41: vaccine potential and protein expression. AB - BACKGROUND: Corynebacterium pseudotuberculosis, a facultative intracellular bacterial pathogen, is the etiological agent of caseous lymphadenitis (CLA), an infectious disease that affects sheep and goats and it is responsible for significant economic losses. The disease is characterized mainly by bacteria induced caseous necrosis in lymphatic glands. New vaccines are needed for reliable control and management of CLA. Thus, the putative virulence factors SpaC, SodC, NanH, and PknG from C. pseudotuberculosis FRC41 may represent new target proteins for vaccine development and pathogenicity studies. RESULTS: SpaC, PknG and NanH presented better vaccine potential than SodC after in silico analyses. A total of 136 B and T cell epitopes were predicted from the four putative virulence factors. A cluster analysis was performed to evaluate the redundancy degree among the sequences of the predicted epitopes; 57 clusters were formed, most of them (34) were single clusters. Two clusters from PknG and one from SpaC grouped epitopes for B and T-cell (MHC I and II). These epitopes can thus potentially stimulate a complete immune response (humoral and cellular) against C. pseudotuberculosis. Several other clusters, including two from NanH, grouped B-cell epitopes with either MHC I or II epitopes. The four target proteins were expressed in Escherichia coli. A purification protocol was developed for PknG expression. CONCLUSIONS: In silico analyses show that the putative virulence factors SpaC, PknG and NanH present good potential for CLA vaccine development. Target proteins were successfully expressed in E. coli. A protocol for PknG purification is described. PMID- 27184576 TI - Quantifying Trace Amounts of Aggregates in Biopharmaceuticals Using Analytical Ultracentrifugation Sedimentation Velocity: Bayesian Analyses and F Statistics. AB - Analytical ultracentrifugation-sedimentation velocity (AUC-SV) is often used to quantify high molar mass species (HMMS) present in biopharmaceuticals. Although these species are often present in trace quantities, they have received significant attention due to their potential immunogenicity. Commonly, AUC-SV data is analyzed as a diffusion-corrected, sedimentation coefficient distribution, or c(s), using SEDFIT to numerically solve Lamm-type equations. SEDFIT also utilizes maximum entropy or Tikhonov-Phillips regularization to further allow the user to determine relevant sample information, including the number of species present, their sedimentation coefficients, and their relative abundance. However, this methodology has several, often unstated, limitations, which may impact the final analysis of protein therapeutics. These include regularization-specific effects, artificial "ripple peaks," and spurious shifts in the sedimentation coefficients. In this investigation, we experimentally verified that an explicit Bayesian approach, as implemented in SEDFIT, can largely correct for these effects. Clear guidelines on how to implement this technique and interpret the resulting data, especially for samples containing micro-heterogeneity (e.g., differential glycosylation), are also provided. In addition, we demonstrated how the Bayesian approach can be combined with F statistics to draw more accurate conclusions and rigorously exclude artifactual peaks. Numerous examples with an antibody and an antibody-drug conjugate were used to illustrate the strengths and drawbacks of each technique. PMID- 27184577 TI - Di-Peptide-Modified Gemini Surfactants as Gene Delivery Vectors: Exploring the Role of the Alkyl Tail in Their Physicochemical Behavior and Biological Activity. AB - The aim of this work was to elucidate the structure-activity relationship of new peptide-modified gemini surfactant-based carriers. Glycyl-lysine modified gemini surfactants that differ in the length and degree of unsaturation of their alkyl tail were used to engineer DNA nano-assemblies. To probe the optimal nitrogen to phosphate (N/P) ratio in the presence of helper lipid, in vitro gene expression and cell toxicity measurements were carried out. Characterization of the nano assemblies was accomplished by measuring the particle size and surface charge. Morphological characteristics and lipid organization were studied by small angle X-ray scattering technique. Lipid monolayers were studied using a Langmuir Blodgett trough. The highest activity of glycyl-lysine modified gemini surfactants was observed with the 16-carbon tail compound at 2.5 N/P ratio, showing a 5- to 10-fold increase in the level of reporter protein compared to the 12 and 18:1 carbon tail compounds. This ratio is significantly lower compared to the previously studied gemini surfactants with alkyl or amino- spacers. In addition, the 16-carbon tail compound exhibited the highest cell viability (85%). This high efficiency is attributed to the lowest critical micelle concentration of the 16-tail gemini surfactant and a balanced packing of the nanoparticles by mixing a saturated and unsaturated lipid together. At the optimal N/P ratio, all nanoparticles exhibited an inverted hexagonal lipid assembly. The results show that the length and nature of the tail of the gemini surfactants play an important role in determining the transgene efficiency of the delivery system. We demonstrated here that the interplay between the headgroup and the nature of tail is specific to each series, thus in the process of rational design, the contribution of the latter should be assessed in the appropriate context. PMID- 27184578 TI - Clinical, Pharmacokinetic, and In Vitro Studies to Support Bioequivalence of Ophthalmic Drug Products. AB - For ophthalmic drug products, the determination of bioequivalence can be challenging, as drug concentrations at the site of action cannot always be measured. The FDA has recommended a variety of studies that can be used to demonstrate bioequivalence for different ophthalmic drug products. Product specific bioequivalence recommendations for 28 ophthalmic products have been posted on FDA's website as of May 2016, outlining the specific tests which should be performed to demonstrate bioequivalence. The type of study that can be used to demonstrate bioequivalence depends on the drug product's active pharmaceutical ingredient(s), dosage form, indication, site of action, mechanism of action, and scientific understanding of drug release/drug availability and drug product characteristics. This article outlines the FDA's current guidance on studies to demonstrate bioequivalence through clinical endpoint studies, pharmacokinetic studies, and in vitro studies for generic ophthalmic drug products. PMID- 27184580 TI - Psychiatric and Behavioural Disorders in Children with Epilepsy (ILAE Task Force Report): Epilepsy and psychosis in children and teenagers. AB - Psychosis related to epilepsy or antiepileptic treatment can occur in teenagers and very rarely in children. Postictal, interictal and antiepileptic-drug-induced psychosis have all been reported in young people. Whether ictal psychosis occurs in this age group remains open to debate. Neuronal antibody encephalitis such as anti-NMDA receptor encephalitis can present with seizures and psychosis, both of which can resolve with prompt, appropriate immunotherapy. In addition, there have been several reports in which the terms psychosis or psychotic features have been used loosely to describe behavioural disturbance in children with epilepsy; in these cases there have apparently been no diagnostic features of psychosis, implying that these terms should not have been used. The management of epilepsy related psychosis in young people is similar to that in adults. Antipsychotic medication should not be withheld if it is needed on clinical grounds. If the psychosis has been induced by antiepileptic medication then a medication review is necessary. PMID- 27184579 TI - The Effects of Pharmaceutical Excipients on Gastrointestinal Tract Metabolic Enzymes and Transporters-an Update. AB - Accumulating evidence from the last decade has shown that many pharmaceutical excipients are not pharmacologically inert but instead have effects on metabolic enzymes and/or drug transporters. Hence, the absorption, distribution, metabolism, and elimination (ADME) of active pharmaceutical ingredients (APIs) may be altered due to the modulation of their metabolism and transport by excipients. The impact of excipients is a potential concern for Biopharmaceutics Classification System (BCS)-based biowaivers, particularly as the BCS-based biowaivers have been extended to class 3 drugs in certain dosage forms. The presence of different excipients or varying amounts of excipients between formulations may result in bio-inequivalence. The excipient impact may lead to significant variations in clinical outcomes as well. The aim of this paper is to review the recent findings of excipient effects on gastrointestinal (GI) absorption, focusing on their interactions with the metabolic enzymes and transporters in the GI tract. A wide range of commonly used excipients such as binders, diluents, fillers, solvents, and surfactants are discussed here. We summarized the reported effects of those excipients on GI tract phase I and phase II enzymes, uptake and efflux transporters, and relevant clinical significance. This information can enhance our understanding of excipient influence on drug absorption and is useful in designing pharmacokinetic studies and evaluating the resultant data. PMID- 27184581 TI - The Expression of the Androgen Receptor and Estrogen Receptor 1 is Related to Sex Dimorphism in the Gerbil Prostate Development. AB - The development of the prostate gland in females has not yet been clearly elucidated, and the sexual dimorphism associated with such gland development in general is far from being understood. In the present study, we used tridimensional (3D) reconstructions and histochemical and immunohistochemical techniques to describe the sexual dimorphism and its causes in the early postnatal development of the prostate in male and female Mongolian gerbils (Meriones unguiculatus). We observed that the female prostate was smaller, had fewer branches throughout the development, and underwent differentiation earlier than that in males. Also, the expression of the estrogen receptor 1 (ESR1 or ER alpha) and fibroblast growth factor 10 (FGF10) was decreased in the periductal region, and the expression of the androgen receptor (AR) was increased in the epithelium. All together, these changes decreased proliferation and branching and led to an earlier prematuration of the female prostate. These new data shed light on the underlying mechanisms involved with the sexual dimorphism in the development of the prostate. Anat Rec, 299:1130-1139, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27184582 TI - Shoulder orthoses for the prevention and reduction of hemiplegic shoulder pain and subluxation: systematic review. AB - OBJECTIVES: To determine whether shoulder orthoses prevent or reduce gleno humeral subluxation and hemiplegic shoulder pain. DATA SOURCES: OVID SP, MEDLINE, AMED, CINAHL, PEDro and the Cochrane Central Register of Controlled Trials. REVIEW METHODS: We included: randomised or quasi-randomised controlled trials, controlled before and after studies and observational studies. Two reviewers independently screened, critically appraised papers using the PEDro tool, and extracted data. A descriptive synthesis was performed as there were insufficient data for meta-analysis. RESULTS: Eight studies were included, totalling 186 participants: One randomised controlled trial with 41 participants, one quasi randomised with 14 participants, one before and after controlled study with 40 participants and five observational studies with 91 participants met the inclusion criteria. Findings suggest that applying an orthosis to an already subluxed shoulder immediately reduced vertical subluxation on X-ray but improvements were not maintained when orthosis was removed. Orthoses with both proximal and distal attachments improved shoulder pain in the majority of stroke patients when worn for four weeks (starting several days or weeks post-stroke). There was no increase in adverse effects of contracture, spasticity or hand oedema when compared to no orthosis. Orthoses were generally well-tolerated and most patients rated the orthosis as comfortable to wear. CONCLUSION: Observational studies suggest that orthoses reduce vertical subluxation whilst in situ. Available evidence from heterogeneous studies after stroke suggests that orthoses may reduce pain and are well-tolerated with prolonged use. No studies have tested whether subluxation and pain can be prevented by immediate post stroke application of orthoses. PMID- 27184583 TI - In vivo evaluation of hybrid patches composed of PLA based copolymers and collagen/chondroitin sulfate for ligament tissue regeneration. AB - Biomaterials for soft tissues regeneration should exhibit sufficient mechanical strength, demonstrating a mechanical behavior similar to natural tissues and should also promote tissues ingrowth. This study was aimed at developing new hybrid patches for ligament tissue regeneration by synergistic incorporation of a knitted structure of degradable polymer fibers to provide mechanical strength and of a biomimetic matrix to help injured tissues regeneration. PLA- Pluronic(r) (PLA-P) and PLA-Tetronic(r) (PLA-T) new copolymers were shaped as knitted patches and were associated with collagen I (Coll) and collagen I/chondroitine-sulfate (Coll CS) 3-dimensional matrices. In vitro study using ligamentocytes showed the beneficial effects of CS on ligamentocytes proliferation. Hybrid patches were then subcutaneously implanted in rats for 4 and 12 weeks. Despite degradation, patches retained strength to answer the mechanical physiological needs. Tissue integration capacity was assessed with histological studies. We showed that copolymers, associated with collagen and chondroitin sulfate sponge, exhibited very good tissue integration and allowed neotissue synthesis after 12 weeks in vivo. To conclude, PLA-P/CollCS and PLA-T/CollCS hybrid patches in terms of structure and composition give good hopes for tendon and ligament regeneration. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1778-1788, 2017. PMID- 27184584 TI - Synthesis of the Peptide Ac-Wahx-KTTKS and Evaluation of the Ability to Induce In Vitro Collagen Synthesis. AB - In this work, we report the synthesis of a peptide analogue of the KTTKS, termed Ac- Wahx-KTTKS and evaluate its cytotoxicity and role in biosynthesis of collagen for future application in skin aging. The peptide was obtained with purity higher than 97.5%. In the cytotoxicity assay, we observed non-toxic effects for Ac-WAhx KTTKS at concentrations below 600 uM for HaCaT and 500 uM for HepG2 cells, respectively. After 24 and 48 h it was possible to observe significant changes in collagen synthesis in the groups treated with various concentrations of the peptide. In conclusion, the Ac-Wahx- KTTKS peptide increased collagen synthesis in fibroblasts by 80% and it is a promising candidate for improving skin aging. PMID- 27184585 TI - The effects of an 8-week computer-based brain training programme on cognitive functioning, QoL and self-efficacy after stroke. AB - Cognitive impairment after stroke has a direct impact on daily functioning and quality of life (QoL) of patients and is associated with higher mortality and healthcare costs. The aim of this study was to determine the effect of a computer based brain training programme on cognitive functioning, QoL and self-efficacy compared to a control condition in stroke patients. Stroke patients with self perceived cognitive impairment were randomly allocated to the intervention or control group. The intervention consisted of an 8-week brain training programme (Lumosity Inc.(r)). The control group received general information about the brain weekly. Assessments consisted of a set of neuropsychological tests and questionnaires. In addition, adherence with trained computer tasks was recorded. No effect of the training was found on cognitive functioning, QoL or self efficacy when compared to the control condition, except for very limited effects on working memory and speed. This study found very limited effects on neuropsychological tests that were closely related to trained computer tasks, but no transfers to other tests or self-perceived cognitive failures, QoL or self efficacy. These findings warrant the need for further research into the value of computer-based brain training to improve cognitive functioning in the chronic phase after stroke. PMID- 27184586 TI - Complex bifurcation lesions: Randomized comparison of a fully bioresorbable modified t stenting strategy versus bifurcation reconstruction with a dedicated self-expanding stent in combination with bioresorbable scaffolds, an OCT study: Rationale and design of the COBRA II trial. AB - OBJECTIVE: There is an ongoing controversy regarding the efficacy and safety of different percutaneous stenting techniques for coronary bifurcation lesions needing >1 stent. The promise of safe vessel restoration with bioresorbable scaffolds (BRS) may not be transferable to complex double BRS bifurcation techniques, and permanent metallic scaffolding of the bifurcation core may be needed. We identified modified-T stenting as the most promising fully bioresorbable 2-stent strategy in a preclinical setting. The objective of this study is to assess acute performance and compare long-term vessel healing with this strategy, versus an approach combining BRS with a dedicated metallic drug eluting bifurcation stent. STUDY DESIGN: In a single center, 60 consecutive patients with true and complex coronary bifurcation lesions will be randomly assigned to treatment with the dedicated self-expanding AxxessTM biolimus-eluting bifurcation stent in the proximal main vessel and additional AbsorbTM everolimus eluting BRS in the branches versus a modified T technique using AbsorbTM only. Angiography and optical coherence tomography (OCT) will be performed immediately after implantation and at 30 months, and clinical follow-up is foreseen up to 5 years after implantation. The primary endpoint is the change in minimal luminal area assessed with OCT from baseline to 30 months in pre-specified bifurcation segments. CONCLUSION: To date the use of AbsorbTM BRS in complex coronary bifurcations has not been evaluated in a randomized clinical trial setting. The COBRA II study will examine the role and safety of a double BRS strategy in coronary bifurcations, alone or in combination with a metallic dedicated bifurcation device. (c) 2016 Wiley Periodicals, Inc. PMID- 27184588 TI - The pursuit of a score to guide mechanical treatment of circulatory failure after cardiac arrest. PMID- 27184589 TI - Click chemistry-assisted, bis-cholesteryl-appended, isosorbide-based, dual responsive organogelators and their self-assemblies. AB - A new series of symmetric, bis-cholesteryl-appended, isosorbide derivatives (BCIE, BCIC2 and BCIC4) were designed as gelators to respond to changes in their environment and were synthesized successfully. Among these derivatives, BCIE can gel a wide variety of organic solvents (23 solvents), suggesting that BCIE acts as a more versatile gelator than BCIC2 and BCIC4. The CGC of the gels varies from 1.53 mM in 1-hexanol to 23 mM in pyridine. The results of the gelation ability in different solvents revealed that changing the linking group (ester/carbamate) attached to the cholesteryl units can produce a dramatic change in the gelation behavior of the compounds. The morphology of the as-formed organogels can be regulated by changing the types of organic solvents. The results from electron microscopy studies revealed that the gelator molecule self-assembled into different aggregates, from wrinkled fibers to dense fibers, with the change of solvents. The gels of BCIE in 1-hexanol and 1-octanol exhibited strong CD (circular dichroism) signals, indicating that the gelation induced supramolecular chirality in these gel systems. Secondary forces of van der Waals and pi-pi stacking (from both 1,2,3-triazole and aromatic units) played important roles in the aggregation of compounds in the solvents according to FTIR and variable temperature (1)H-NMR analysis, and a mechanism for the gel formation was proposed. The gel-to-sol phase transition can be triggered by the addition of trifluoroacetic acid (TFA), and the gel state was obtained slowly (after 1 day) when neutralizing with triethyl amine (TEA), which indicated that the sol ? gel phase transitions are tunable by pH, which is further supported by (1)H-NMR and SEM analysis. In addition, the gel stability of BCIE was investigated using Cu(2+), Cd(2+), Ag(2+), Fe(3+), Hg(2+), Mg(2+), Pd(2+), Al(3+) and Zn(2+), and the results showed that the gel-to-sol phase transition process could be selectively controlled by interaction with Pd(2+) and Zn(2+) because complexation with 1,2,3-triazoles destroyed the interactions between the triazoles, collapsing the gel, which was further evidenced by (1)H-NMR and SEM analysis. However, the gel stability of BCIE was enhanced by the addition of Pd(2+) and Zn(2+) in the presence of pyridine, whereas the gel collapsed in other solvents, which may be due to the chelating effect of the pyridine moiety. Another interesting feature of this gel is that when using the gelator as a stabilizer, stable water in oil (W/O) gel-emulsions were created, in which styrene can be used as the continuous phase and water as the dispersed phase with the stabilizer in the continuous phase of only 2% (w/v). Gel-emulsions were observed with any ratio of water to styrene. PMID- 27184590 TI - A measure of association for ordered categorical data in population-based studies. AB - Ordinal classification scales are commonly used to define a patient's disease status in screening and diagnostic tests such as mammography. Challenges arise in agreement studies when evaluating the association between many raters' classifications of patients' disease or health status when an ordered categorical scale is used. In this paper, we describe a population-based approach and chance corrected measure of association to evaluate the strength of relationship between multiple raters' ordinal classifications where any number of raters can be accommodated. In contrast to Shrout and Fleiss' intraclass correlation coefficient, the proposed measure of association is invariant with respect to changes in disease prevalence. We demonstrate how unique characteristics of individual raters can be explored using random effects. Simulation studies are conducted to demonstrate the properties of the proposed method under varying assumptions. The methods are applied to two large-scale agreement studies of breast cancer screening and prostate cancer severity. PMID- 27184587 TI - The italian limb girdle muscular dystrophy registry: Relative frequency, clinical features, and differential diagnosis. AB - INTRODUCTION: Limb girdle muscular dystrophies (LGMDs) are characterized by high molecular heterogeneity, clinical overlap, and a paucity of specific biomarkers. Their molecular definition is fundamental for prognostic and therapeutic purposes. METHODS: We created an Italian LGMD registry that included 370 molecularly defined patients. We reviewed detailed retrospective and prospective data and compared each LGMD subtype for differential diagnosis purposes. RESULTS: LGMD types 2A and 2B are the most frequent forms in Italy. The ages at disease onset, clinical progression, and cardiac and respiratory involvement can vary greatly between each LGMD subtype. In a set of extensively studied patients, targeted next-generation sequencing (NGS) identified mutations in 36.5% of cases. CONCLUSION: Detailed clinical characterization combined with muscle tissue analysis is fundamental to guide differential diagnosis and to address molecular tests. NGS is useful for diagnosing forms without specific biomarkers, although, at least in our study cohort, several LGMD disease mechanisms remain to be identified. Muscle Nerve 55: 55-68, 2017. PMID- 27184591 TI - The effect of continuous wound infusion of ropivacaine on postoperative pain after median sternotomy and mediastinal drain in children. AB - BACKGROUND: Postoperative pain after median sternotomy is usually treated with i.v. opioids. We hypothesized that continuous wound infusion of ropivacaine decreases postoperative morphine consumption and improves analgesia in children who undergo cardiac surgery. METHODS: This randomized, double-blind study comprised 49 children aged 1-9 years who underwent atrial septal defect (ASD) closure. Patients received continuous local anesthetic wound infiltration either with 0.2% ropivacaine, 0.3-0.4 mg.kg(-1) .h(-1) (Group R) or with saline (Group C). Rescue morphine consumption, Objective Pain Scale (OPS), time to mobilization, time to enteral food intake, and time to discharge were recorded. RESULTS: There were no statistically significant differences in morphine consumption at 24, 48, and 72 h postsurgery between R and C groups. There was a weak evidence for a difference in the time to the first morphine administration after tracheal extubation to be longer for Group R than Group C (186.2 vs 81.0 min; 95% CI (-236.5, 26.2), P = 0.114). The incidence of nausea and vomiting were comparable between the groups. No signs or symptoms of local anesthetic toxicity were registered. CONCLUSIONS: Contrary to our hypothesis, continuous ropivacaine wound infusion did not reduce morphine consumption, pain score values, or nausea and vomiting in children who underwent ASD closure with median sternotomy and mediastinal drain. PMID- 27184593 TI - Adsorptive removal of emerging polyfluoroalky substances F-53B and PFOS by anion exchange resin: A comparative study. AB - Chrome plating is an important emission source of perfluorinated compounds (PFCs) industrial uses in China, where two commercial products potassium 2-(6-chloro 1,1,2,2,3,3,4,4,5,5,6,6-dodecafluorohexyloxy) (F-53B) and perfluorooctane sulfonate (PFOS) are applied as mist suppressant, causing non-negligible environmental risk. In this paper, anion-exchange resin IRA67 was evaluated for F 53B and PFOS removal from simulated and actual wastewater. Adsorption kinetics exhibited higher adsorption velocity and capacity of IRA67 for PFOS than F-53B due to their difference in molecular structures. Adsorption isotherms demonstrated the adsorption capacity of F-53B and PFOS on IRA67 was 4.2mmol/g and 5.5mmol/g, respectively. Because of the deprotonating of amine groups, solution pH had significant effect on IRA67 at pH>10. The results indicated that besides anion exchange other interactions including hydrophobic interaction and the formation of micelles or hemi-micelles were all involved in adsorption process. Coexisting sulfate and chromate in wastewater decreased adsorption capacities of F-53B and PFOS. The spent resin could be regenerated by the NaCl/NaOH and methanol mixed solution. In the mixed system and actual wastewater IRA67 can simultaneously remove F-53B and PFOS without obvious preference but the removal percent can be affected by competitive effect. PMID- 27184592 TI - Prechewing infant food, consumption of sweets and dairy and not breastfeeding are associated with increased diarrhoea risk of 10-month-old infants in the United States. AB - Prechewing of food by caregivers is a common infant feeding practice both globally and in the United States, where the highest rates of the practice are found among African-Americans and Alaska Natives. The objective of this study was to determine if prechewing of infant food is associated with increased diarrhoea prevalence of 10-month-old infants in the United States. The study used cross sectional data from the Infant Feeding Practices Study II to test for associations between prechewing and 2-week-period prevalence of infant diarrhoea. At 10 months of age, infants who received prechewed food (n = 203) had a diarrhoea prevalence of 16.1%, compared with 10.9% of children who did not receive prechewed food (n = 1567) [relative risk (RR) = 1.48, 95% confidence interval (CI) 1.03-2.11]. After adjusting for covariates, including breastfeeding and consuming sweets and dairy, prechewing was associated with a 58% higher risk (RR = 1.58, 95% CI 1.10-2.26) of 2-week diarrhoea prevalence. Consumption of sweets (RR = 1.35, 95% CI 1.03-1.78) and dairy (RR = 1.41, 95% CI 1.03-1.93) was also associated with increased diarrhoea risk. Continued breastfeeding at 10 months of age was associated with a reduced risk of diarrhoea (RR = 0.68, 95% CI 0.50-0.91). Prechewing of infant food is associated with increased diarrhoea among 10-month-old infants. The high RR found in this study suggests that prechewing may be an important factor in public health efforts to reduce the burden of diarrhoeal disease. However, further research is needed to establish that prechewing causes increased diarrhoea risk and to explore potential benefits of prechewing. PMID- 27184594 TI - Complication rates of completion lymphadenectomy following positive sentinel lymph node biopsy versus therapeutic lymphadenectomy in melanoma. PMID- 27184595 TI - Hyperosmosis and its combination with nutrient-limitation are novel environmental stressors for induction of triacylglycerol accumulation in cells of Chlorella kessleri. AB - Triacylglycerols of oleaginous algae are promising for production of food oils and biodiesel fuel. Air-drying of cells induces triacylglycerol accumulation in a freshwater green alga, Chlorella kessleri, therefore, it seems that dehydration, i.e., intracellular hyperosmosis, and/or nutrient-limitation are key stressors. We explored this possibility in liquid-culturing C. kessleri cells. Strong hyperosmosis with 0.9 M sorbitol or 0.45 M NaCl for two days caused cells to increase the triacylglycerol content in total lipids from 1.5 to 48.5 and 75.3 mol%, respectively, on a fatty acid basis, whereas nutrient-limitation caused its accumulation to 41.4 mol%. Even weak hyperosmosis with 0.3 M sorbitol or 0.15 M NaCl, when nutrient-limitation was simultaneously imposed, induced triacylglycerol accumulation to 61.9 and 65.7 mol%, respectively. Furthermore, culturing in three-fold diluted seawater, the chemical composition of which resembled that of the medium for the combinatory stress, enabled the cells to accumulate triacylglycerol up to 24.7 weight% of dry cells in only three days. Consequently, it was found that hyperosmosis is a novel stressor for triacylglycerol accumulation, and that weak hyperosmosis, together with nutrient limitation, exerts a strong stimulating effect on triacylglycerol accumulation. A similar combinatory stress would contribute to the triacylglycerol accumulation in air-dried C. kessleri cells. PMID- 27184600 TI - Engineering Bandgaps of Monolayer MoS2 and WS2 on Fluoropolymer Substrates by Electrostatically Tuned Many-Body Effects. AB - Intrinsic electrical and excitonic properties of monolayer transition-metal dichalcogenides can be revealed on CYTOP fluoropolymer substrates with greatly suppressed unintentional doping and dielectric screening. Ambipolar transport behavior is observed in monolayer WS2 by applying solid-state back gates. The excitonic properties of monolayer MoS2 and WS2 are determined by intricate interplays between the bandgap renormalization, Pauli blocking, and carrier screening against carrier doping. PMID- 27184601 TI - Adrenomedullin mediates tumor necrosis factor-alpha-induced responses in dorsal root ganglia in rats. AB - Adrenomedullin (AM), a member of the calcitonin gene-related peptide (CGRP) family, has been demonstrated to be a pain peptide. This study investigated the possible involvement of AM in tumor necrosis factor-alpha (TNF-alpha)-induced responses contributing to neuronal plasticity in the dorsal root ganglia (DRG). Exposure of the DRG explant cultures to TNF-alpha (5nM) for 48h upregulated the expression of AM mRNA. The treatment with TNF-alpha also increased the level of CGRP, CCL-2 and MMP-9 mRNA in the cultured DRG. This increase was attenuated by the co-treatment with the selective AM receptor antagonist AM22-52 (2MUM). The blockade of AM receptors inhibited TNF-alpha-induced increase of the glial fibrillary acidic protein (GFAP), interleukin-1beta (IL-1beta), phosphorylated cAMP response element binding protein (pCREB) and nuclear factor kappa B (pNF kappaB) proteins. On the other hand, the treatment with the AM receptor agonist AM1-50 (10nM) for 96h induced an increase in the level of GFAP, IL-1beta, pCREB and pNF-kappaB proteins. The inhibition of AM activity did not change TNF-alpha induced phosphorylation of extracellular signal-related kinase (pERK) while the treatment with AM1-50 still increased the level of pERK in the cultured DRG. Immunofluorescence assay showed the colocalization of AM-like immunoreactivity (IR) with TNF-alpha-IR in DRG neurons. The present study suggests that the increased AM receptor signaling mediated the many, but not all, TNF-alpha-induced activities, contributing to peripheral sensitization in neuropathic pain. PMID- 27184599 TI - Coming of age: ten years of next-generation sequencing technologies. AB - Since the completion of the human genome project in 2003, extraordinary progress has been made in genome sequencing technologies, which has led to a decreased cost per megabase and an increase in the number and diversity of sequenced genomes. An astonishing complexity of genome architecture has been revealed, bringing these sequencing technologies to even greater advancements. Some approaches maximize the number of bases sequenced in the least amount of time, generating a wealth of data that can be used to understand increasingly complex phenotypes. Alternatively, other approaches now aim to sequence longer contiguous pieces of DNA, which are essential for resolving structurally complex regions. These and other strategies are providing researchers and clinicians a variety of tools to probe genomes in greater depth, leading to an enhanced understanding of how genome sequence variants underlie phenotype and disease. PMID- 27184602 TI - Prevalence of colonic diverticulosis in mainland China from 2004 to 2014. AB - The aim of this study was to determine the prevalence of colonic diverticulosis in mainland China. Sixty two thousand and thirty-four colonoscopies performed between Jan 2004 and Dec 2014 were reviewed retrospectively. The overall diverticulosis prevalence was 1.97% and out of this, 85.3% was right-sided. Prevalence does not change, significantly, on trends between the period 2004 2014. The peak of prevalence of diverticulosis was compared between the female group aged >70 years to the male one of 41-50 years. The other peak, otherwise, was compared between the group of 51-60 years with the right-sided diverticulosis to the one of >70 years with left-sided disease. Multivariate analysis suggested that the male gender could be a risk factor for diverticulosis in the group aged <=70 years, but not for the older patients. In addition, among men was registered an increased risk factor for right-sided diverticulosis and, at the same time, a protective one for left-sided localization. In conclusion, the prevalence of colonic diverticulosis is very low in mainland China and it does not change significantly on trends over the time. Both the prevalence of this condition and its distribution changes according to the age and the genders. These findings may lead the researchers to investigate the mechanisms causing this kind of disease and its distribution in regard of the age and the gender. PMID- 27184603 TI - Reply to Letter: Using novel risk stratification statistics to better understand the value of screening tests. PMID- 27184604 TI - Occult Metastases in Pelvic Lymphadenectomy Specimens From Patients With Urothelial Carcinoma of the Bladder. AB - OBJECTIVE: To identify occult metastases within lymph nodes (LNs) reported as negative by routine histologic evaluation. In patients with high-grade, muscle invasive urothelial carcinoma (UC) of the bladder, pelvic lymphadenectomy during radical cystectomy demonstrates a survival advantage, increasing with the number of LNs removed, even if negative for metastatic disease. This finding may potentially be explained by the presence of occult metastases. MATERIALS AND METHODS: Radical cystectomy specimens with high-grade UC invading the perivesical tissue and negative LNs (pT3N0) between 2000 and 2014 were reviewed. Five levels were cut for each LN block. Two sections were cut per level: 1 stained for hematoxylin and eosin and 1 for AE1/AE3. Micrometastases were defined as tumor deposits >0.2 mm but <2 mm. Isolated tumor cells were defined as <=0.2 mm. Medical records and survival data were reviewed. RESULTS: We identified 21 cases, consisting of 370 lymph nodes. Six of 21 patients (29%) had occult metastases, including 5 occult metastatic UC and 1 occult metastatic prostate adenocarcinoma. There were 10 positive LNs; 2 macrometastases, 2 micrometastases, and 6 with ITCs. Two of 6 patients (33%) had lymphovascular invasion identified in the primary tumor. Kaplan-Meier analysis showed no significant difference in overall survival between the group of patients who remained N0 versus those upstaged due to discovery of occult metastases (P-value = .42). CONCLUSION: In patients with pT3 UC undergoing cystectomy, we demonstrated the presence of occult metastases in 29% of patients. The high percentage of occult metastases present in these cases possibly explains the proven survival advantage of removing "negative" LNs. This finding might also have implications in the histologic evaluation of LNs. PMID- 27184607 TI - A robust operational model for predicting where tropical cyclone waves damage coral reefs. AB - Tropical cyclone (TC) waves can severely damage coral reefs. Models that predict where to find such damage (the 'damage zone') enable reef managers to: 1) target management responses after major TCs in near-real time to promote recovery at severely damaged sites; and 2) identify spatial patterns in historic TC exposure to explain habitat condition trajectories. For damage models to meet these needs, they must be valid for TCs of varying intensity, circulation size and duration. Here, we map damage zones for 46 TCs that crossed Australia's Great Barrier Reef from 1985-2015 using three models - including one we develop which extends the capability of the others. We ground truth model performance with field data of wave damage from seven TCs of varying characteristics. The model we develop (4MW) out-performed the other models at capturing all incidences of known damage. The next best performing model (AHF) both under-predicted and over-predicted damage for TCs of various types. 4MW and AHF produce strikingly different spatial and temporal patterns of damage potential when used to reconstruct past TCs from 1985 2015. The 4MW model greatly enhances both of the main capabilities TC damage models provide to managers, and is useful wherever TCs and coral reefs co-occur. PMID- 27184605 TI - Coadministration of disulfiram and lorazepam in the treatment of alcohol dependence and co-occurring anxiety disorder: an open-label pilot study. AB - BACKGROUND: Anxiety is common among persons with alcohol use disorder during early abstinence from alcohol. Although benzodiazepines are effective for short term treatment of anxiety, they are rarely used beyond acute detoxification due to concerns about misuse or interactions with alcohol. OBJECTIVES: We conducted an open-label trial to explore the effects of coadministering lorazepam and disulfiram to alcohol-dependent patients with anxiety disorder symptoms. The rationale for this model is to minimize the risks of the benzodiazepine, while also potentially enhancing adherence to disulfiram. METHODS: Forty-one participants with DSM-IV alcohol dependence who also met syndromal criteria for anxiety disorder with or without co-occurring major depressive syndrome initiated treatment with lorazepam (starting dose 0.5 mg three times daily) and disulfiram (starting dose 500 mg three times weekly). Participants received 16 weeks of monitored pharmacotherapy with manualized medical management. RESULTS: Adherence to treatment decreased steadily with time (85.4% at 4 weeks, 36.6% at 16 weeks). Participants showed significant increases in percent abstinent days during treatment and at 24 weeks follow-up. Large reductions in anxiety, depression, and craving were observed during treatment, and improvement remained significant at 24 weeks. Duration of adherence with disulfiram strongly predicted abstinence at 16 weeks. There was no evidence of misuse of lorazepam or dose escalation during the study. CONCLUSION: Lorazepam can be safely used for short-term treatment of anxiety in combination with disulfiram treatment of alcohol use disorder. However, it is not clear that making lorazepam dispensing contingent on adherence to disulfiram enhances retention in disulfiram treatment. PMID- 27184608 TI - Antioxidant power as a quality control marker for completeness of amotosalen and ultraviolet A photochemical treatments in platelet concentrates and plasma units. AB - BACKGROUND: Pathogen inactivation treatments such as INTERCEPT aim to make sure blood and blood-derived products are free of pathogens before using them for transfusion purposes. At present, there is no established quality control assay that assesses the completeness of the treatment. As INTERCEPT is a photochemical treatment known to generate reactive oxygen species we sought to use the antioxidant power (AOP) of the blood product as a marker of treatment execution. In this perspective, we evaluated an electrochemically based miniaturized system, the EDEL technology, for measuring the AOP in both platelet concentrates (PCs) and plasma. STUDY DESIGN AND METHODS: Aliquots were withdrawn from PCs or plasma units before and after INTERCEPT treatment and a few microliters were directly deposited into the EDEL sensor for the AOP measurement. The result is expressed in EDEL, an arbitrary unit (micromolar equivalent of ascorbic acid). RESULTS: The INTERCEPT treatment resulted in a significant decrease of the AOP. An AOP threshold of 66.5, 89.0, 59.8, and 131.5 EDEL was determined for apheresis PCs collected from female and male donors, buffy coat PCs, and plasma units, respectively. Below the threshold value, INTERCEPT treatment is considered to be executed. Additionally, we showed that the presence of the photosensitizer in combination with the ultraviolet A illumination is required to observe the AOP decrease. CONCLUSION: The measurement of the AOP of PCs and plasma units can be used to document the completeness of the INTERCEPT treatment. PMID- 27184606 TI - Randomized Clinical Trial for Early Postoperative Complications of Ex-PRESS Implantation versus Trabeculectomy: Complications Postoperatively of Ex-PRESS versus Trabeculectomy Study (CPETS). AB - We compared early postoperative complications between trabeculectomy and Ex-PRESS implantation. Enrolled patients with 39 primary open-angle or 25 exfoliative glaucoma were randomly assigned to receive trabeculectomy (trabeculectomy group) or Ex-PRESS implantation (Ex-PRESS group). Primary outcomes were early postoperative complications, including postoperative anterior chamber inflammation, frequencies of hyphema, flat anterior chamber, choroidal detachment, hypotonic maculopathy, and the change of visual acuity. The postoperative flare values in trabeculectomy group were higher than those in the Ex-PRESS group (overall, P = 0.004; and 10 days, P = 0.02). Hyphema occurred significantly more frequently in the trabeculectomy group (P = 0.0025). There were no significant differences of the other primary outcomes between the two groups. Additionally, duration of anterior chamber opening was significantly shorter in the Ex-PRESS group (P = 0.0002) and the eyes that had iris contact with Ex-PRESS tube had significantly shallower anterior chambers than did the eyes without the iris contact (P = 0.013). The Ex-PRESS implantation prevented early postoperative inflammation and hyphema in the anterior chamber and shortened the duration of anterior chamber opening. Iris contact with the Ex PRESS tube occurred more frequently in eyes with open-angle glaucoma and shallow anterior chambers. PMID- 27184609 TI - A new view on the codonocarpine type alkaloids of Capparis decidua. AB - Several spermidine alkaloids are described in literature as constituents of the root bark of Capparis decidua. Since some of the proposed structures, however, are in conflict with the expected biosynthetic paths, an extract of the root bark of the plant was re-investigated. Four major spermidine alkaloids of the codonocarpine type were identified and their structures elucidated: of the four compounds, isocodonocarpine was described previously for C. decidua and cadabicine was proposed as a possible constituent as well. Codonocarpine was found for the first time in an extract of C. decidua but was previously isolated from a closely related plant. Capparidisinine, finally, is an alkaloid with a structure that has never been described before. The structures of the four alkaloids are substantiated by NMR and MS data, and the four compounds are in logical agreement with biosynthetic considerations: they would arise from alpha,omega-bis-adducts of spermidine with coumaric and/or ferulic acids, followed by phenol oxidation. PMID- 27184610 TI - A drive system to add standing mobility to a manual standing wheelchair. AB - Current manual standing wheelchairs are not mobile in the standing position. The addition of standing mobility may lead to improved health and function for the user and may increase utilization of standing wheelchairs. In this project, a chain drive system was fitted to a manual standing wheelchair, adding mobility in the standing position. The hand rims are accessible from both seated and standing positions. The prototype uses 16-inch drive wheels in front with casters in the rear. Additional anterior casters are elevated when seated for navigating obstacles and then descend when standing to create a six-wheeled base with extended anterior support. Stability testing shows the center of pressure remains within the base of support when leaning to the sides or front in both seated and standing positions. Four veterans with spinal cord injury provided feedback on the design and reported that mobility during standing was very important or extremely important to them. The veterans liked the perceived stability and mobility of the prototype and provided feedback for future refinements. For example, reducing the overall width (width from hand rim to hand rim) and weight could make this system more functional for users. PMID- 27184611 TI - COPD: A controversial disease? PMID- 27184612 TI - Early versus delayed post-operative bathing or showering to prevent wound complications: a Cochrane review summary. PMID- 27184613 TI - Molecular characterization of environmental Cryptococcus neoformans VNII isolates in Jos, Plateau State, Nigeria. AB - Cryptococcus neoformans and Cryptococcus gattii are encapsulated yeasts able to cause fatal neurological infections in both human and other mammals. Cryptococcosis is the most common fungal infection of the central nervous system and has a huge burden in sub-Saharan Africa and South East Asia. Bird excreta are considered an environmental reservoir for C. neoformans in urban areas, therefore a study aimed at isolating and characterizing this yeast is important in disease management. In this study, one hundred samples of pigeon droppings were collected in Jos, Plateau State, Nigeria. C. neoformans was isolated from three samples and initially identified using standard phenotypic and biochemical tests. Molecular analysis revealed that all three isolates belonged to C. neoformans genotype VNII, mating type alpha and were assigned to the sequence type ST43 by multilocus sequence typing analysis. This study reports, for the first time, the molecular characterization of C. neoformans in Nigeria, where little is still known about the environmental distribution of the genotypes, serotypes and mating types of this important human pathogen. PMID- 27184614 TI - Fungal interdigital tinea pedis in Dakar (Senegal). AB - Fungal interdigital tinea pedis (FITP) is the most frequent dermatomycosis in industrial countries. In African tropics, it's a rare motive of consultation and is discovered while complicated. The aims of this article were: to determine the frequency of interdigital tinea pedis among overall mycological analysis in our laboratory; to study epidemiological, clinical and mycological aspects of FITP in outpatients attending the Le Dantec mycology laboratory in Dakar. A total of 62 males (60%) and 42 females (40%), mean age: 43.15 years (range: 11-81 years), were received from January 2011 to December 2015 for suspicion of FITP. Skin specimens were taken from all patients for microscopy and fungal culture. The frequency of ITP represents 5.6% (104/1851) among our overall mycological analysis. FITP was confirmed in 68 patients (SPI=65.38%), mainly located between the 4th and 5th toes and 71 fungal species were isolated (CPI=68.27%). Among patients with confirmed FITP, there were 38 males (56%) and 30 females (44%). The prevalence was highest in patients between 44 and 54 years (26%). Candida albicans, Fusarium solani and Trichophyton interdigitale were shown to be the most common pathogens respectively for yeasts (39%), non-dermatophytic filamentous fungi (NDFF; 21%) and dermatophytes (11%). So FITP isn't a common reason for consultation in Dakar but its simple parasitic index (SPI) is still very high and dermatophytes formerly the main causative agents are being relegated to third place behind yeasts and NDFF. PMID- 27184615 TI - Resveratrol Pretreatment Protected against Cerebral Ischemia/Reperfusion Injury in Rats via Expansion of T Regulatory Cells. AB - BACKGROUND: It is well accepted that repetitive resveratrol (RV) pretreatment (PRC) exerts neuroprotective effect on ischemic stroke. RV was shown to be able to enhance the production of T regulatory cells (Tregs) in autoimmune diseases whereas Tregs are considered to be the cerebroprotective immunomodulator in ischemic stroke. Thus, we hypothesized whether Tregs contributed to PRC-induced neuroprotection against cerebral ischemia/reperfusion (I/R) injury. METHODS: Cerebral I/R injury was induced by middle cerebral artery occlusion for 90 minutes in rats. Adult male Sprague-Dawley rats were randomly assigned to 2 groups: I/R and RV I/R. RV (50 mg/kg) was administrated intraperitoneally once a day for 7 days prior to ischemia onset. RESULTS: PRC significantly ameliorated neurological defects and reduced cerebral infarct volume, accompanied by the significantly increased frequencies of Tregs in the spleens and ischemic hemisphere, the significantly increased levels of interleukin-10 (IL-10) in the plasma and ischemic hemisphere, and the significantly decreased levels of tumor necrosis factor-alpha and IL-6 in the plasma and ischemic hemisphere at 24 hours after ischemia onset. In addition, we also found that PRC significantly improved the frequency and suppressive function of Tregs in the spleens prior to ischemia onset. CONCLUSIONS: Thus, PRC-induced neuroprotection was in part mediated by more Treg accumulation and activation in vivo prior to ischemia onset except for less inflammation response at 24 hours after ischemia onset. PMID- 27184616 TI - Association of Brachial-Ankle Pulse Wave Velocity with Asymptomatic Intracranial Arterial Stenosis in Hypertension Patients. AB - BACKGROUND: Intracranial arterial stenosis is a common cause of ischemic stroke in Asians. We therefore sought to explore the relationship of brachial-ankle pulse wave velocity and intracranial arterial stenosis in 834 stroke-free hypertensive patients. METHODS: Intracranial arterial stenosis was evaluated through computerized tomographic angiography. Brachial-ankle pulse wave velocity was measured by an automated cuff device. RESULTS: The top decile of brachial ankle pulse wave velocity was significantly associated with intracranial arterial stenosis (P = .027, odds ratio = 1.82; 95% confidence interval: 1.07-3.10). The patients with the top decile of brachial-ankle pulse wave velocity showed 56% higher risk for the presence of intracranial arterial stenosis to the whole population, which was more significant in patients younger than 65 years old. We also found that brachial-ankle pulse wave velocity related to both intracranial arterial stenosis and homocysteine. CONCLUSION: Our study showed the association of brachial-ankle pulse wave velocity with asymptomatic intracranial arterial stenosis in hypertension patients, especially in relative younger subjects. Brachial-ankle pulse wave velocity might be a relatively simple and repeatable measurement to detect hypertension patients in high risk of intracranial arterial stenosis. PMID- 27184617 TI - Producing microbial polyhydroxyalkanoate (PHA) biopolyesters in a sustainable manner. AB - Sustainable production of microbial polyhydroxyalkanoate (PHA) biopolyesters on a larger scale has to consider the "four magic e": economic, ethical, environmental, and engineering aspects. Moreover, sustainability of PHA production can be quantified by modern tools of Life Cycle Assessment. Economic issues are to a large extent affected by the applied production mode, downstream processing, and, most of all, by the selection of carbon-rich raw materials as feedstocks for PHA production by safe and naturally occurring wild type microorganisms. In order to comply with ethics, such raw materials should be used which do not interfere with human nutrition and animal feed supply chains, and shall be convertible towards accessible carbon feedstocks by simple methods of upstream processing. Examples were identified in carbon-rich waste materials from various industrial braches closely connected to food production. Therefore, the article shines a light on hetero-, mixo-, and autotrophic PHA production based on various industrial residues from different branches. Emphasis is devoted to the integration of PHA-production based on selected raw materials into the holistic patterns of sustainability; this encompasses the choice of new, powerful microbial production strains, non-hazardous, environmentally benign methods for PHA recovery, and reutilization of waste streams from the PHA production process itself. PMID- 27184618 TI - Immobilised cells of Pachysolen tannophilus yeast for ethanol production from crude glycerol. AB - Screening among naturally occurring yeast strains of Pachysolen spp. that are capable of producing ethanol from glycerol under aerobic conditions identified the most active culture, P. tannophilus Y -475. Conversion of glycerol by this producer immobilised in poly(vinyl alcohol) cryogel resulted in a 90% yield of ethanol relative to the theoretical limit. The maximum rate of alcohol accumulation was 0.64+/-0.01gL-1h-1 at a 25gL-1 concentration of glycerol in the culture medium. We demonstrated the efficacy of reusing immobilised cells (for a minimum of 16 working cycles for batch mode of crude glycerol conversion to ethanol) and the possibility of long-term (for a minimum of 140h) use of the cells in continuous mode with a maximum process productivity of 0.63+/-0.02gL-1h 1, while the medium dilution rate in the reactor was 0.062+/-0.001h-1. Reduction of metabolic activity did not exceed 5-7% relative to baseline. Immobilised cells were demonstrated to withstand long-term storage in frozen form for at least 2 years while retaining high metabolic activity. PMID- 27184619 TI - Bt cotton and employment effects for female agricultural laborers in Pakistan. AB - The literature about economic and social impacts of Bt cotton adoption on farm households in developing countries is growing. Yet, there is still uncertainty about wider implications of this technology for rural development, including effects for landless rural laborers. Bt-related yield advantages may lead to intensified production and higher demand for labor. Building on farm survey data collected in Pakistan and using double-hurdle regression models, we analyze employment effects of Bt cotton adoption. Model estimates show that Bt adoption has increased the demand for hired labor by 55%. Manual harvesting, which is common in Pakistan, is a labor-intensive activity primarily carried out by female laborers. Accordingly, gender disaggregation shows that the employment-generating effects are particularly strong for women, who often belong to the most disadvantaged groups of rural societies. These results suggest that Bt technology can contribute to additional employment income for the poor and to more equitable rural development. PMID- 27184620 TI - Binding of oxime group to uranyl ion. AB - Currently, the leading approach for extraction of uranium from seawater is selective sorption of UO2(2+) ions onto a poly(acrylamidoxime) fiber. Amidoxime functional groups are the most studied extractant moieties for this application, but are not perfectly selective, and understanding how these groups (and more generally the oxime groups) interact with UO2(2+) and competing ions in seawater is an important step in designing better extractants. We have started a new research programme aiming at in-depth studies of the uranyl-oxime/amidoxime interactions and we report here our first results which cover aspects of the coordination chemistry of 2-pyridyl ketoximes towards UO2(2+). Detailed synthetic investigations of various UO2(2+)/mepaoH and UO2(2+)/phpaoH reaction systems (mepaoH is methyl 2-pyridyl ketoxime and phpaoH is phenyl 2-pyridyl ketoxime) have provided access to the complexes [UO2(mepao)2(MeOH)2]{[UO2(NO3)(mepao)(MeOH)2]}2 (), [UO2(mepao)2(MeOH)2] (), [(UO2)2(O2)(O2CMe)2(mepaoH)2] () and [UO2(phpao)2(MeOH)2] (). The peroxido group in , which was isolated without the addition of external peroxide sources, probably arises from a bis(aquo)- and/or bis(hydroxido)-bridged diuranyl precursor in solution followed by photochemical oxidation of the bridging groups. The U(VI) atom in the [UO2(NO3)(mepao)(MeOH)2] molecules of () is surrounded by one nitrogen and seven oxygen atoms in a very distorted hexagonal bipyramidal geometry; two oxygen atoms from the terminal MeOH ligands, two oxygen atoms from the bidentate chelating nitrato group, and the oxygen and nitrogen atoms from the eta(2) oximate group of the 1.110 (Harris notation) mepao(-) ligand define the equatorial plane. This plane consists of two terminal MeOH ligands and two eta(2) oximate groups in the [UO2(mepao)2(MeOH)2] molecule () of . The structure of the [UO2(mepao)2(MeOH)2] molecule that is present in is very similar to the structure of the corresponding molecule in . The structure of the dinuclear molecule that is present in consists of two {UO2(O2CMe)(mepaoH)}(+) units bridged by a eta(2):eta(2):MU O2(2-) group. The equatorial plane of each uranyl site is composed of the pyridyl and oxime nitrogen atoms of a 1.011 mepaoH ligand, the oxygen atoms of an almost symmetrically coordinated bidentate chelating MeCO2(-) group and the two oxygen atoms of the peroxido groups. The core molecular structure of is similar to that of , the only difference being the presence of 1.110 phpao(-) ligands in the former instead of mepao(-) groups in the latter. The free pyridyl nitrogen atoms of mepao(-) and phpao(-) ligands of , and are acceptors of intramolecular H bonds from the ligated MeOH oxygen atoms. H-bonding and pi-pi stacking interactions build interesting supramolecular networks in the crystal structures of the four complexes. Compounds are the first structurally characterized uranyl complexes with 2-pyridyl aldoximes or ketoximes as ligands. IR data are discussed in terms of the coordination modes of the ligands in the complexes. (1)H NMR data in DMSO-d6 suggest that the complexes decompose in solution. The ESI(-) MS spectrum of dissolved in the NH4(O2CMe) buffer is indicative of the presence of [UO2(O2CMe)3](-), [UO2(O2CMe)2(phpao)](-), [UO2(O2CMe)(phpao)2](-) and [UO2(phpao)3](-) species. A common structural motif of the complexes containing the anionic mepao(-) (, ) and phpao(-) () ligands is that the deprotonated oximate group prefers to bind in the eta(2) fashion forming a 3-membered chelating ring in spite of the presence of a pyridyl nitrogen atom, whose coordination would be expected to lead to 5- or 6-membered chelating rings. PMID- 27184621 TI - Brain Tumor Genetic Modification Yields Increased Resistance to Paclitaxel in Physical Confinement. AB - Brain tumor cells remain highly resistant to radiation and chemotherapy, particularly malignant and secondary cancers. In this study, we utilized microchannel devices to examine the effect of a confined environment on the viability and drug resistance of the following brain cancer cell lines: primary cancers (glioblastoma multiforme and neuroblastoma), human brain cancer cell lines (D54 and D54-EGFRvIII), and genetically modified mouse astrocytes (wild type, p53-/-, p53-/- PTEN-/-, p53-/- Braf, and p53-/- PTEN-/- Braf). We found that loss of PTEN combined with Braf activation resulted in higher viability in narrow microchannels. In addition, Braf conferred increased resistance to the microtubule-stabilizing drug Taxol in narrow confinement. Similarly, survival of D54-EGFRvIII cells was unaffected following treatment with Taxol, whereas the viability of D54 cells was reduced by 75% under these conditions. Taken together, our data suggests key targets for anticancer drugs based on cellular genotypes and their specific survival phenotypes during confined migration. PMID- 27184622 TI - Cost-effectiveness analysis of quadrivalent influenza vaccine in Spain. AB - Influenza has a major impact on healthcare systems and society, but can be prevented using vaccination. The World Health Organization (WHO) currently recommends that influenza vaccines should include at least two virus A and one virus B lineage (trivalent vaccine; TIV). A new quadrivalent vaccine (QIV), which includes an additional B virus strain, received regulatory approval and is now recommended by several countries. The present study estimates the cost effectiveness of replacing TIVs with QIV for risk groups and elderly population in Spain. A static, lifetime, multi-cohort Markov model with a one-year cycle time was adapted to assess the costs and health outcomes associated with a switch from TIV to QIV. The model followed a cohort vaccinated each year according to health authority recommendations, for the duration of their lives. National epidemiological data allowed the determination of whether the B strain included in TIVs matched the circulating one. Societal perspective was considered, costs and outcomes were discounted at 3% and one-way and probabilistic sensitivity analyses were performed. Compared to TIVs, QIV reduced more influenza cases and influenza-related complications and deaths during periods of B-mismatch strains in the TIV. The incremental cost-effectiveness ratio (ICER) was 8,748?/quality adjusted life year (QALY). One-way sensitivity analysis showed mismatch with the B lineage included in the TIV was the main driver for ICER. Probabilistic sensitivity analysis shows ICER below 30,000?/QALY in 96% of simulations. Replacing TIVs with QIV in Spain could improve influenza prevention by avoiding B virus mismatch and provide a cost-effective healthcare intervention. PMID- 27184623 TI - Second Allogeneic Stem Cell Transplantation for Acute Leukemia Using a Chemotherapy-Only Cytoreduction with Clofarabine, Melphalan, and Thiotepa. AB - Relapse after allogeneic hematopoietic stem cell transplantation (alloHSCT) remains one of the leading causes of mortality in patients with leukemia. Treatment options in this population remain limited, with concern for both increased toxicity and further relapse. We treated 18 patients with acute leukemia for marrow +/- extramedullary relapse after a previous alloHSCT with a myeloablative cytoreductive regimen including clofarabine, melphalan, and thiotepa followed by a second or third transplantation from the same or a different donor. All patients were in remission at the time of the second or third transplantation. All evaluable patients engrafted. The most common toxicity was reversible transaminitis associated with clofarabine. Two patients died from transplantation-related causes. Seven patients relapsed after their second or third transplanation and died of disease. Nine of 18 patients are alive and disease free, with a 3-year 49% probability of overall survival (OS). Patients whose remission duration after initial alloHSCT was >6 months achieved superior outcomes (3-year OS, 74%, 95% confidence interval, 53% to 100%), compared with those relapsing within 6 months (0%) (P < .001). This new cytoreductive regimen has yielded promising results with acceptable toxicity for second or third transplantations in patients with high-risk acute leukemia who relapsed after a prior transplantation, using various graft and donor options. This approach merits further evaluation in collaborative group studies. PMID- 27184626 TI - Precision (in Language and) Medicine. PMID- 27184624 TI - Administrative Claims Data for Economic Analyses in Hematopoietic Cell Transplantation: Challenges and Opportunities. AB - There is an increasing need for the development of approaches to measure quality, costs, and resource utilization patterns among allogeneic hematopoietic cell transplantation (HCT) patients. Administrative claims data provide an opportunity to examine service utilization and costs, particularly from the payer's perspective. However, because administrative claims data are primarily designed for reimbursement purposes, challenges arise when using it for research. We use a case study with data derived from the 2007 to 2011 Truven Health MarketScan Research database to discuss opportunities and challenges for the use of administrative claims data to examine the costs and service utilization of allogeneic HCT and chemotherapy alone for patients with acute myeloid leukemia (AML). Starting with a cohort of 29,915 potentially eligible patients with a diagnosis of AML, we were able to identify 211 patients treated with HCT and 774 treated with chemotherapy alone where we were sufficiently confident of the diagnosis and treatment path to allow analysis. Administrative claims data provide an avenue to meet the need for health care costs, resource utilization, and outcome information. However, when using these data, a balance between clinical knowledge and applied methods is critical to identifying a valid study cohort and accurate measures of costs and resource utilization. PMID- 27184627 TI - Financial Hardship and Patient-Reported Outcomes after Hematopoietic Cell Transplantation. AB - Although hematopoietic cell transplantation (HCT) is the only curative therapy for many advanced hematologic cancers, little is known about the financial hardship experienced by HCT patients nor the association of hardship with patient reported outcomes. We mailed a 43-item survey to adult patients approximately 180 days after their first autologous or allogeneic HCT at 3 high-volume centers. We assessed decreases in household income; difficulty with HCT-related costs, such as need to relocate or travel; and 2 types of hardship: hardship_1 (reporting 1 or 2 of the following: dissatisfaction with present finances, difficulty meeting monthly bill payments, or not having enough money at the end of the month) and "hardship_2" (reporting all 3). Patient-reported stress was measured with the Perceived Stress Scale-4, and 7-point scales were provided for perceptions of overall quality of life (QOL) and health. In total, 325 of 499 surveys (65.1%) were received. The median days since HCT was 173; 47% underwent an allogeneic HCT, 60% were male, 51% were > 60 years old, and 92% were white. Overall, 46% reported income decline after HCT, 56% reported hardship_1, and 15% reported hardship_2. In multivariable models controlling for income, those reporting difficulty paying for HCT-related costs were more likely to report financial hardship (odds ratio, 6.9; 95% confidence interval, 3.8 to 12.3). Hardship_1 was associated with QOL below the median (odds ratio, 2.9; 95% confidence interval, 1.7 to 4.9), health status below the median (odds ratio, 2.2; 95% confidence interval, 1.3 to 3.6), and stress above the median (odds ratio, 2.1; 95% confidence interval, 1.3 to 3.5). In this sizable cohort of HCT patients, financial hardship was prevalent and associated with worse QOL and higher levels of perceived stress. Interventions to address patient financial hardship especially those that ameliorate HCT-specific costs-are likely to improve patient reported outcomes. PMID- 27184628 TI - A Three-Site Mechanism for Agonist/Antagonist Selective Binding to Vasopressin Receptors. AB - Molecular-dynamics simulations with metadynamics enhanced sampling reveal three distinct binding sites for arginine vasopressin (AVP) within its V2 -receptor (V2 R). Two of these, the vestibule and intermediate sites, block (antagonize) the receptor, and the third is the orthosteric activation (agonist) site. The contacts found for the orthosteric site satisfy all the requirements deduced from mutagenesis experiments. Metadynamics simulations for V2 R and its V1a R-analog give an excellent correlation with experimental binding free energies by assuming that the most stable binding site in the simulations corresponds to the experimental binding free energy in each case. The resulting three-site mechanism separates agonists from antagonists and explains subtype selectivity. PMID- 27184625 TI - Metabolic Syndrome and Cardiovascular Disease after Hematopoietic Cell Transplantation: Screening and Preventive Practice Recommendations from the CIBMTR and EBMT. AB - Metabolic syndrome (MetS) is a constellation of cardiovascular risk factors that increases the risk of cardiovascular disease, diabetes mellitus, and all-cause mortality. Long-term survivors of hematopoietic cell transplantation (HCT) have a substantial risk of developing MetS and cardiovascular disease, with an estimated prevalence of MetS of 31% to 49% among HCT recipients. Although MetS has not yet been proven to impact cardiovascular risk after HCT, an understanding of the incidence and risk factors for MetS in HCT recipients can provide the foundation to evaluate screening guidelines and develop interventions that may mitigate cardiovascular-related mortality. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal to review literature and recommend practices appropriate to HCT recipients. Here we deliver consensus recommendations to help clinicians provide screening and preventive care for MetS and cardiovascular disease among HCT recipients. All HCT survivors should be advised of the risks of MetS and encouraged to undergo recommended screening based on their predisposition and ongoing risk factors. PMID- 27184630 TI - Hierarchical Assemblies of Carbon Nanotubes for Ultraflexible Li-Ion Batteries. AB - The flexible batteries that are needed to power flexible circuits and displays remain challenging, despite considerable progress in the fabrication of such devices. Here, it is shown that flexible batteries can be fabricated using arrays of carbon nanotube microstructures, which decouple stress from the energy-storage material. It is found that this battery architecture imparts exceptional flexibility (radius ~ 300 MUm), high rate (20 A g(-1) ), and excellent cycling stability. PMID- 27184629 TI - Single-Reaction Multiplex Reverse Transcription PCR for Detection of Zika, Chikungunya, and Dengue Viruses. AB - Clinical manifestations of Zika virus, chikungunya virus, and dengue virus infections can be similar. To improve virus detection, streamline molecular workflow, and decrease test costs, we developed and evaluated a multiplex real time reverse transcription PCR for these viruses. PMID- 27184632 TI - Is vitamin e or ursodeoxycholic acid a valid treatment option for nonalcoholic fatty liver disease in 2016? PMID- 27184633 TI - Contrast enhanced ultrasound for solid pancreatic lesions: Does timing after contrast injection also matter? PMID- 27184631 TI - Clozapine metabolites protect dopaminergic neurons through inhibition of microglial NADPH oxidase. AB - BACKGROUND: Clozapine, an atypical antipsychotic medication, has been effectively used to treat refractory schizophrenia. However, the clinical usage of clozapine is limited due to a high incidence of neutropenia or agranulocytosis. We previously reported that clozapine protected dopaminergic neurons through inhibition of microglial activation. The purpose of this study was to explore the neuroprotective effects of clozapine metabolites clozapine N-oxide (CNO) and N desmethylclozapine (NDC), as well as their propensity to cause neutropenia. METHODS: The primary midbrain neuron-glia culture was applied to detect the neuroprotective and anti-inflammatory effect of clozapine and its metabolites in lipopolysaccharide (LPS) and MPP(+)-induced toxicity. And the subsequent mechanism was demonstrated by gp91 (phox) mutant cell cultures as well as microgliosis cell lines. In vivo, to confirm the neuroprotective effect of clozapine and CNO, we measured the dopaminergic neuronal loss and rotarod motor deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-generated mouse Parkinson's disease (PD) model. The neutropenia or agranulocytosis of clozapine and its metabolites was illustrated by white blood cell count of the treated mice. RESULTS: We found that, in midbrain neuron-glia cultures, CNO and NDC were more potent than clozapine in protecting dopaminergic neurons against LPS and MPP(+)-induced toxicity. CNO and NDC-afforded neuroprotection was linked to inhibition of microglia-mediated neuroinflammation, as demonstrated by abolished neuroprotection in microglia-depleted cultures and their capacity of inhibiting LPS-induced release of proinflammatory factors from activated microglia. NADPH oxidase (NOX2) was subsequently recognized as the main target of CNO and NDC since genetic ablation of gp91 (phox) , the catalytic subunit of NOX2, abolished their neuroprotective effects. CNO and NDC inhibited NOX2 activation through interfering with the membrane translocation of the NOX2 cytosolic subunit, p47 (phox) . The neuroprotective effects of CNO were further verified in vivo as shown by attenuation of dopaminergic neurodegeneration, motor deficits, and reactive microgliosis in MPTP-generated mouse PD model. More importantly, unlike clozapine, CNO did not lower the white blood cell count. CONCLUSIONS: Altogether, our results show that clozapine metabolites elicited neuroprotection through inactivation of microglia by inhibiting NOX2. The robust neuroprotective effects and lack of neutropenia suggest that clozapine metabolites may be promising candidates for potential therapy for neurodegenerative diseases. PMID- 27184634 TI - Management of hepatitis c genotype 4 in the liver transplant setting. AB - End-stage liver disease secondary to hepatitis C virus (HCV) infection is the major indication for orthotopic liver transplantation (OLT) worldwide. The percentage of HCV patients infected with genotype 4 (G4) among recipients of OLT varies depending on geographic location. In the Middle East, including Saudi Arabia, G4 infection is the most common genotype among transplant recipients. Due to the low prevalence of HCV-G4 in Europe and the United States, this genotype has not been adequately studied in prospective trials evaluating treatment outcomes and remains the least studied variant. The aim of this review is to summarize the natural history and treatment outcome of HCV-G4 following liver transplantation, with particular attention to new HCV therapies. This review incorporates all published studies and abstracts including HCV-G4 patients. PMID- 27184635 TI - Implementation of the simple endoscopic activity score in crohn's disease. AB - Simple Endoscopic Score for Crohn's Disease (SES-CD) was developed as an attempt to simplify Crohn's Disease Endoscopic Index of Severity (CDEIS). Since it was constructed from CDEIS, SES-CD performs comparably but also carries similar limitations. Several studies have utilized SES-CD scoring to describe disease severity or response to therapy. Some of them used SES-CD score as a continuous variable while others utilized certain cutoff values to define severity grades. All SES-CD cutoff values reported in published clinical trials were empirically selected by experts. Although in most of the studies that used SEC-CD scoring to define disease severity, a score <3 reflected inactive disease, no study is using score 0 to predefine inactivity. Studies applying SES-CD to define response to treatment used score 0. There is no optimal SES-CD cut-off for endoscopic remission. The quantification of mucosal healing using SES-CD scoring has not been standardized yet. As the definition of mucosal healing by SES-CD is unset, the concept of deep remission is also still evolving. Serum and fecal biomarkers as well as new radiologic imaging techniques are complementary to SES-CD. Current practice as well as important changes in endoscopy should be taken into consideration when defining SES-CD cutoffs. The optimal timing of SES-CD scoring to assess mucosal healing is not defined yet. To conclude, SES-CD represents a valuable tool. However, a consensus agreement on its optimal use is required. PMID- 27184636 TI - An open-label randomized control study to compare the efficacy of vitamin e versus ursodeoxycholic acid in nondiabetic and noncirrhotic Indian NAFLD patients. AB - BACKGROUND/AIM: The study was carried out to compare the efficacy of Vitamin E versus Ursodeoxycholic acid (UDCA) in nondiabetic nonalcoholic fatty liver disease (NAFLD) patients. PATIENTS AND METHODS: We randomized 250 non cirrhotic and non diabetic NAFLD patients diagnosed on ultrasound, with raised alanine aminotransferase (ALT) level. (>40 IU/L), to receive Vitamin E 400 mg twice a day (Group A) or UDCA 300 mg twice a day (Group B) for 52 weeks. Lifestyle modification to achieve at least 5% weight reduction and subsequent weight control and regular exercise was advised to both groups. The primary study endpoint was normalization of ALT. Secondary endpoints were the proportion of patients with reduction in ALT, relative reduction in the NAFLD Fibrosis score (NFS), symptomatic improvement and tolerability. RESULTS: One hundred and fifty patients received UDCA as compared to 100 patients receiving Vitamin E. The treatment groups were comparable at entry with regard to age (44.1 vs 42.4 years), gender (67% vs 63% female), risk factors for nonalcoholic steatohepatitis, hypochondriac pain, serum liver biochemistries, and NAFLD Fibrosis score. The primary endpoint was achieved in 21 (14%) and 19 (19%) of patients in Group A and Group B, respectively (P = 0.2). The proportion of patients with reduction in ALT (56% vs 63%, P = 0.2), symptomatic improvement (78% vs 67%, P= 0.058), reduction in the NFS (44% vs 47%, P= 0.69), and tolerability (98% vs 95%, P= 0.2) were similar between Group A and Group B, respectively. CONCLUSION: UDCA is an effective and safe alternative to Vitamin E in nondiabetic-noncirrhotic Indian NAFLD patients. PMID- 27184637 TI - Efficacy of contrast-enhanced harmonic endoscopic ultrasonography in the diagnosis of pancreatic ductal carcinoma. AB - BACKGROUND/AIMS: Distinguishing pancreatic ductal carcinoma (DC) from other pancreatic masses remains challenging. This study aims at evaluating the efficacy of contrast-enhanced harmonic endoscopic ultrasonography (CEH-EUS) in the diagnosis of DC. PATIENTS AND METHODS: Forty-nine patients with solid pancreatic mass lesions underwent CEH-EUS. EUS (B-mode) was used to evaluate the inner echoes, distributions, and borders of the masses. The vascular patterns of the masses were evaluated with CEH-EUS at 30-50 s (early phase) and 70-90 s (late phase) after the administration of Sonazoid(r). RESULTS: The final diagnoses included DCs (37), mass-forming pancreatitis (6), endocrine neoplasms (3), a solid pseudopapillary neoplasm (1), a metastatic carcinoma (1), and an acinar cell carcinoma (1). The sensitivity, specificity, and accuracy of the diagnoses of DC in hypoechoic masses using EUS (B-mode) were 89.2%, 16.7%, and 71.4%, respectively. The sensitivity, specificity, and accuracy for the diagnosis of DC in hypovascular masses using CEH-EUS were 73.0%, 91.7%, and 77.6% in the early phase and 83.8%, 91.7%, and 85.7% in the late phase, respectively. CONCLUSIONS: CEH-EUS for the diagnosis of DC is superior to EUS. CEH-EUS in the late phase was particularly efficacious in the diagnosis of DC. PMID- 27184638 TI - Outcome of acute upper gastrointestinal bleeding in patients with coronary artery disease: A matched case-control study. AB - BACKGROUND/AIM: The risk of upper gastrointestinal bleeding (UGIB) increases in patients with coronary artery disease (CAD) due to the frequent use of antiplatelets. There is some data reporting on treatment outcomes in CAD patients presenting with UGIB. We aim to determine the clinical characteristics and outcomes of UGIB in patients with CAD, compared with non-CAD patients. PATIENTS AND METHODS: We conducted a prospective multi-center cohort study (THAI UGIB 2010) that enrolled 981 consecutive hospitalized patients with acute UGIB. A matched case-control analysis using this database, which was collected from 11 tertiary referral hospitals in Thailand between January 2010 and September 2011, was performed. RESULT: Of 981 hospitalized patients with UGIB, there were 61 CAD patients and 244 gender-matched non-CAD patients (ratio 1:4). UGIB patients with CAD were significantly older, and had more frequently used antiplatelets and warfarin than in non-CAD patients. Compared with non-CAD, the CAD patients had significantly higher Glasgow-Blatchford score, full and pre-endoscopic Rockall score and full. Peptic ulcer in CAD patients was identified more often than in non-CAD patients. UGIB patients with CAD and non-CAD had similar outcomes with regard to mortality rate, re-bleeding, surgery, embolization, and packed erythrocyte transfusion. However, CAD patients had longer duration of hospital stays than non-CAD patients. Two CAD patients died from cardiac arrest after endoscopy, whereas three non-CAD patients died from pneumonia and acute renal failure during their hospitalization. CONCLUSION: In Thailand, patients presenting with UGIB, concomitant CAD did not affect clinical outcome of treatment, compared with non-CAD patients, except for longer hospital stay. PMID- 27184639 TI - Are serum quantitative hepatitis b surface antigen levels, liver histopathology and viral loads related in chronic hepatitis b-infected patients? AB - BACKGROUND/AIMS: Fluctuations in hepatitis B virus (HBV) DNA and alanine transaminase (ALT) levels complicate assessment of the phases of chronic hepatitis B (CHB) infection and correct identification of the inactive HBV carrier state. In this study, we aimed to examine the role of HBsAg quantification (qHBsAg) in the identification of the phases of HBV and to evaluate its association with liver histopathology. PATIENTS AND METHODS: Inactive HBV carriers (IC) (n = 104) and CHB patients (n = 100) were enrolled in the study. Demographic characteristics of patients were evaluated; biochemical parameters and serum qHBsAg levels were studied, and liver biopsy and histopathology were assessed. RESULTS: Serum qHBsAg levels were found to be significantly low in IC (5150.78 +/- 8473.16 IU/mL) compared with the HBeAg negative CHB (7503.21 +/- 8101.41 IU/mL) (P = 0.001) patients. The diagnostic accuracy of qHBsAg to differentiate HBeAg-negative CHB from IC was found to be moderate (c-statistic: 0.695) and the cutoff level for qHBsAg in diagnosis was found as 1625 IU/mL (specificity: 80%; sensitivity: 49%). No correlation was noted between serum qHBsAg level and ALT, histologic activity index (HAI), and fibrosis in IC and CHB. A moderate and positive correlation was observed between the serum qHBsAg level and HBV-DNA in HBeAg-positive CHB patients. CONCLUSIONS: Serum qHBsAg levels may prove to be useful in the differentiation between IC and HBeAg-negative CHB when used in conjunction with HBV DNA. Furthermore, patients diagnosed solely on the basis of HBV DNA and ALT may present with higher grade and stage of liver histopathology than expected. PMID- 27184640 TI - Hepatitis b virus expression and replication in ovum and the influencing factors. AB - BACKGROUND/AIM: The aim of this study was to investigate the factors that influence hepatitis B virus (HBV) expression and replication in the ovum. MATERIALS AND METHODS: Immunohistochemistry and in situ hybridization techniques were used to assay the distributions of HBcAg, HBV DNA, and HBV mRNA in ovarian tissues and the ovum in 50 patients with chronic HBV infection. HBeAg and HBV DNA in the serum were also detected. Comparisons of categorical data were performed using McNemar test. RESULTS: The positive rates of HBcAg, HBV DNA, and HBV mRNA in ovum and ovarian tissues of high replication group were significantly higher than low replication group (chi2 = 15.04, P< 0.05; chi2 = 12.96, P<0.05; chi2 = 19.36, P< 0.05; respectively). High positive rates of HBcAg, HBV DNA, and HBV mRNA in ovum and ovarian tissues were found in women with HBeAg-positive than HBeAg-negative (chi2 = 113.14,P< 0.05; chi2 = 11.13, P< 0.05; chi2 = 17.39, P< 0.05; respectively). CONCLUSION: HBV can infect and replicate in the ovary and ovum. Maternal HBeAg status and HBV DNA levels are important influencing factors. PMID- 27184641 TI - No mortality difference following treatment with terlipressin or somatostatin in cirrhotic patients with gastric variceal hemorrhage. AB - BACKGROUND/AIMS: The aim of this study was to compare the efficacy of terlipressin versus somatostatin as adjuvants to endoscopic treatment in cirrhotic patients with gastric variceal bleeding. PATIENTS AND METHODS: The National Health Insurance Database, derived from the Taiwan National Health Insurance Program, was used to enroll patients who were discharged with International Classification of Diseases, 9th Revision, Clinical Modification diagnoses of cirrhosis and who underwent gastric variceal sclerotherapy for gastric variceal bleeding between January 1, 2007, and December 31, 2007. We observed treatment outcomes and identified clinical factors associated with mortality. RESULTS: In total, we enrolled 311 cirrhosis patients who underwent sclerotherapy for active gastric variceal bleeding. Among them, 218 patients received terlipressin, and 93 patients received somatostatin. The overall 30 day mortality rate was 13.2% (41/311). A total of 78 (25.1%) patients underwent second-look endoscopy, but only 12 (7%) needed a second course of gastric variceal sclerotherapy. The overall 30-day mortality rates for patients treated with terlipressin and somatostatin were 13.3% and 12.9%, respectively, showing no statistically significant differences between outcomes in the two treatment groups (P = 0.672). The risk of 30-day mortality was significantly higher in patients with hepatocellular carcinoma (HR: 3.257, 95% CI: 1.640-6.469, P= 0.001), acute renal failure (HR: 6.261, 95% CI: 2.376-16.499, P< 0.001), or hepatic encephalopathy (HR: 3.091, 95% CI: 1.430-6.680, P= 0.004). CONCLUSIONS: Mortality rates did not differ significantly between cirrhosis patients with acute gastric variceal bleeding who received somatostatin or terlipressin as adjuvants to endoscopy. PMID- 27184643 TI - Expression of serotonin receptors in the colonic tissue of chronic diarrhea rats. AB - BACKGROUND/AIMS: This study aimed to investigate the difference among the expression of serotonin receptors (5-HT3, 5-HT4, and 5-HT7receptors) in colonic tissue of chronic diarrhea rats. MATERIALS AND METHODS: A rat model of chronic diarrhea was established by lactose diet. The expression of 5-HT3, 5-HT4, and 5 HT7receptors in the colonic tissue was detected using immunohistochemistry, real time PCR and Western blotting techniques. RESULTS: There is no significant difference on the protein expression of 5-HT3receptor between the normal group and the chronic diarrhea model group. The mRNA expression of 5-HT3receptor in the chronic diarrhea model group was significantly lower than that in the normal group (n = 10; P< 0.01). The protein and mRNA expression of 5-HT4receptor in the chronic diarrhea model group were significantly higher than those in the normal group (n = 10; P< 0.05, P< 0.01). On the contrary, the protein and mRNA expressions of 5-HT7receptor in the chronic diarrhea model group were significantly decreased compared with the normal group (n = 10; P< 0.01, P< 0.01). CONCLUSIONS: The results suggested the receptors of 5-HT4and 5-HT7may be involved in inducing diarrhea by lactose diet. PMID- 27184642 TI - Protective effect of the methanolic extract of malva parviflora l. leaves on acetic acid-induced ulcerative colitis in rats. AB - BACKGROUND/AIMS: Inflammatory bowel disease (IBD) is a general term describing chronic, idiopathic relapsing, inflammatory conditions of the gastrointestinal tract of unknown etiology. Previous studies have indicated that Malva parviflora leaf extract possesses anti-inflammatory, antioxidant, and antiulcerogenic activity. activity. This work aimed to investigatee the anti-inflammatory effect of the methanolic (MEMP) and aqueous (AEMP) extracts of M. parviflora leaves on acetic acid-induced colitis in rats. MATERIALS AND METHODS: 42 male Wistar albino rats were divided into seven groups (n = 6). Group I: Normal saline control group with no colitis; Group II: Acetic acid colitis group; Group III: 100 mg/kg/5 d MEMP; Group IV: 200 mg/kg/5 d.MEMP; Group V: 100 mg/kg/5 d AEMP; Group VI: 200 mg/kg/5 d AEMP; Group VII: Prednisolone group (2 mg/kg/5 d). Treatments were followed by induction of colitis using intrarectal instillation of 2 mL of 4% acetic acid. Colon damage was evaluated macroscopically (spleen weight/body weight, colon weight/length ratio) and the histological changes were also recorded. RESULTS: The results of this study showed that acetic acid caused severe inflammation of the colon and a significant increase in spleen weight/body weight, and an increase in colon weight/length ratio compared with normal control group. Pretreatment with MEMP and AEMP for 5 days followed by induction of colitis resulted in a significant attenuation of spleen weight and colon weight/length ratio compared with acetic acid control group. Methanolic extract provided better anticolitic effect than aqueous extract; the effect was prominent at the dose of 200 mg/kg. Histopathological findings confirmed the protective effect of the MEMP. CONCLUSION: In conclusion, MEMP could ameliorate mucosal damage in experimentally induced colitis when given orally. PMID- 27184646 TI - Automated construction of an intraoperative high-dose-rate treatment plan library for the Varian brachytherapy treatment planning system. AB - PURPOSE: The ability to create treatment plans for intraoperative high-dose-rate (IOHDR) brachytherapy is limited by lack of imaging and time constraints. An automated method for creation of a library of high-dose-rate brachytherapy plans that can be used with standard planar applicators in the intraoperative setting is highly desirable. METHODS AND MATERIALS: Nonnegative least squares algebraic methods were used to identify dwell time values for flat, rectangular planar applicators. The planar applicators ranged in length and width from 2 cm to 25 cm. Plans were optimized to deliver an absorbed dose of 10 Gy to three different depths from the patient surface: 0 cm, 0.5 cm, and 1.0 cm. Software was written to calculate the optimized dwell times and insert dwell times and positions into a .XML plan template that can be imported into the Varian brachytherapy treatment planning system. The user may import the .XML template into the treatment planning system in the intraoperative setting to match the patient applicator size and prescribed treatment depth. RESULTS: A total of 1587 library plans were created for IOHDR brachytherapy. Median plan generation time was approximately 1 minute per plan. Plan dose was typically 100% +/- 1% (mean, standard deviation) of the prescribed dose over the entire length and width of the applicator. Plan uniformity was best for prescription depths of 0 cm and 0.5 cm from the patient surface. CONCLUSIONS: An IOHDR plan library may be created using automated methods. Thousands of plan templates may be optimized and prepared in a few hours to accommodate different applicator sizes and treatment depths and reduce treatment planning time. The automated method also enforces dwell time symmetry for symmetrical applicator geometries, which simplifies quality assurance. PMID- 27184644 TI - Hepatitis c virus genotype 4 replication in the hepatocellular carcinoma cell line HepG2/C3A. AB - BACKGROUND/AIMS: The lack of a reliable cell culture system allowing persistent in vitro hepatitis C virus (HCV) propagation is still restraining the search for novel antiviral strategies. HepG2 cells transfection with HCV allows for viral replication. However, the replication is weak presumably because of HepG2 lack of miRNA-122, which is essential for viral replication. Other agents such as polyethylene glycol (PEG) and dimethyl sulfoxide (DMSO) have been shown to increase the efficiency of infection with other viruses. This study included comparison of HCV genotype 4 5'UTR and core RNA levels and HCV core protein expression at different time intervals in the absence or presence of PEG and/or DMSO postinfection. MATERIALS AND METHODS: We used serum with native HCV particles in infecting HepG2 cells in vitro. HCV replication was assessed by reverse transcriptase polymerase chain reaction for detection of HCV RNA and immunofluorescence and flow cytometry for detection of HCV core protein. RESULTS: HCV 5'UTR and core RNA expression was evident at different time intervals after viral infection, especially after cells were treated with PEG. HCV core protein was also evident at different time intervals using both immunofluorescence and flow cytometry. PEG, not DMSO, has increased the HCV core protein expression in the treated cells, similar to its effect on viral RNA expression. CONCLUSIONS: These expression profiles suggest that the current model of cultured HepG2 cells allows the study of HCV genotype 4 replication and different stages of the viral life cycle. PMID- 27184645 TI - Dose distribution for gynecological brachytherapy with dose accumulation between insertions: Feasibility study. AB - PURPOSE: For gynecological treatments, it is standard to acquire CT images and preferably also MR images before each treatment to calculate the dose of the day. The dose of the complete treatment is calculated by adding the dose metrics of each fraction. It makes the conservative assumption that the same part of the organs at risk always receives the highest dose. The dose calculated this way often limits the prescription dose or the target coverage. We investigated the use of deformable image registration (DIR) as an alternative method to assess the cumulative dose for a treatment course. METHODS AND MATERIALS: Rigid registration is preformed on CT images, followed by DIR. DIR can be based either solely on the three-dimensional images or combined with organ contours. To improve DIR in the pelvic region with low CT contrast, we propose (1) using contours drawn on CT or (2) modifying artificially the contrast in certain volumes. The dose matrix from fraction_n (n > 1) is deformed using a calculated deformation field. RESULTS: The use of the contrast-enhanced images or of contour information helps to guide the DIR. However, because of the very high dose gradients involved in brachytherapy, the uncertainty on the accumulated dose remains of the order of 5-10%. Even for good contour matching, a small local error in the deformation can have significant consequences for the dose distribution. CONCLUSIONS: Using DIR, based on image features and contours, allows to accumulate the dose from different brachytherapy fractions. A robust validation procedure should be developed. PMID- 27184647 TI - Glutamate ameliorates copper-induced oxidative injury by regulating antioxidant defences in fish intestine. AB - The objective of this study was to determine the protective effect of glutamate (Glu) in Cu-induced oxidative injury in fish intestine in vivo and enterocytes in vitro. The results indicated that exposure to 6 mg/l Cu for 72 h induced the production of reactive oxygen species, thereby increasing protein oxidation and lipid peroxidation in enterocytes of grass carp in vitro. Cells exposed to Cu alone resulted in a significant increase in lactate dehydrogenase release, which is accompanied by depletions of antioxidants, including total superoxide dismutase (T-SOD), glutathione S-transferase (GST), glutathione reductase (GR), anti-superoxide anion (ASA), anti-hydroxy radical (AHR) activities and GSH content. Pre-treatment with Glu remarkably prevented the toxic effects of Cu on the T-SOD, GST, GR, AHR, and ASA activities and GSH content in enterocytes. However, Cu induced an adaptive increase in the activities of catalase and glutathione peroxidase (GPx). Glu supplementation further increased GPx activity in enterocytes. Interestingly, the experiment in vivo showed that Glu pre supplementation significantly elevated SOD, GPx, GST, GR, ASA and AHR activities, as well as GSH content. Further results showed that pre-treatment with Glu could alleviate Cu-induced oxidative injury by elevating antioxidant enzyme activities through regulating the expression of NF-E2-related nuclear factor 2 (Nrf2) mRNA. Together, these results indicated that Glu could attenuate Cu-induced cellular oxidative damage in fish intestine, likely mediated through Nrf2 signalling pathways regulating mRNA expressions of antioxidant enzyme genes and synthesis of GSH. PMID- 27184648 TI - Lymphocyte-depleting induction and steroid minimization after kidney transplantation: A review. AB - Steroid minimization after kidney transplantation has become more widely practiced as transplant clinicians seek the potential benefits such as reduced cardiovascular risk factors, improved growth in pediatric patients, and improved compliance with the immunosuppression regimen. Steroid avoidance (i.e. no steroids after the first week) is generally favored compared to later withdrawal. Induction therapy is routine in this setting, frequently rabbit antithymocyte globulin (rATG, Thymoglobulin(r)) or off-license use of alemtuzumab. Direct comparisons of steroid minimization regimens versus standard steroid regimens are rare. However, the available data show that the risk of acute rejection is low when rATG or alemtuzumab induction is given to support steroid-avoidance regimens after kidney transplantation. Steroid avoidance may be inadvisable in patients at high immunological risk or at risk of recurrent glomerular disease. Steroid withdrawal after day 8 may be possible without additional risk of rejection in patients given rATG induction, but while encouraging, the data are too sparse for firm conclusions. In summary, steroid avoidance may be beneficial for patients after renal transplantation, with the potential to avoid or reduce steroid related comorbidities. Whilst depleting induction therapy could be the treatment of choice, results of prospective randomized, controlled studies are eagerly awaited. PMID- 27184649 TI - Long-term safety in living kidney donors for paediatric transplantation. Single centre prospective study. AB - INTRODUCTION: There is enough evidence concerning the short-term safety of living donors after kidney transplantation. However, long-term complications continue to be studied, with a particular interest in young donors. Previous studies have been conducted in older donors for adult renal patients. We present a study of long-term complications in kidney donors for our paediatric population. METHODS: We carried out a long-term donor study for the 54 living kidney-donor transplantations performed at our department from 1979 to June 2014. We monitored the glomerular filtration rate (GFR) on the basis of 24-hour urine creatinine clearance, 24-hour proteinuria and the development of arterial hypertension in the 48 donors who were followed up for more than one year. Only the 39 patients who were exclusively followed up by our department have been included in the results analysis. RESULTS: GFR through creatinine clearance was stable after an initial decrease. No proteinuria was observed in any of the cases. One patient developed chronic kidney disease (CKD), which resulted in a cumulative incidence of 2%. GFR below 60mL/min/1.73 m2 was not reported in any other patients. Arterial hypertension was diagnosed in 25% of donors, 90% of which were treated with antihypertensives. CONCLUSIONS: Risk of CKD and hypertension in living kidney donors for paediatric recipients, who are carefully monitored throughout their evolution, is similar to that of the general population. Therefore, this technique appears to be safe in both the short and long term. PMID- 27184650 TI - Bispyridinium non-oximes: An evaluation of cardiac effects in isolated hearts and smooth muscle relaxing effects in jejunum. AB - Bispyridinium non-oximes seem to be promising candidates for the generic treatment of nerve agent poisoning as they interact with nicotinic and muscarinic acetylcholine receptors. The lead compound MB327 showed therapeutic effectiveness in vitro and in vivo but was toxic at higher doses. In the present study, the effect of various bispyridinium non-oximes on isolated heart and small intestine function was investigated. Bispyridinium non-oximes and oximes were tested in at least seven different concentrations in rat jejunum preparations pre-treated with carbachol. All bispyridinium non-oximes showed classical dose response curves with MB327 being the most effective (EC50=6.6MUM) and MB782 being slightly less effective (EC50=10.4MUM). Neither the bispyridinium non-oximes nor the oximes showed cardiotoxic effects in the isolated Langendorff heart. The tested bispyridinum compounds showed no direct cardiac effect but had variable smooth muscle relaxing effects. Further in vivo studies are required to get more insight into potential toxic mechanisms of these promising nerve agent antidotes. PMID- 27184651 TI - Used water and nutrients: Recovery perspectives in a 'panta rhei' context. AB - There is an urgent need to secure global supplies in safe water and proteinaceous food in an eco-sustainable manner, as manifested from tensions in the nexus Nutrients-Energy-Water-Environment-Land. This paper is concept based and provides solutions based on resource recovery from municipal and industrial wastewater and from manure. A set of decisive factors is reviewed facilitating an attractive business case. Our key message is that a robust barrier must clear the recovered product from its original status. Besides refined inorganic fertilizers, a central role for five types of microbial protein is proposed. A resource cycling solution for the extremely confined environment of space habitation should serve as an incentive to assimilate a new user mindset. To achieve the ambitious goal of sustainable food security, the solutions suggested here need a broad implementation, hand in hand with minimizing losses along the entire fertilizer feed-food-fork chain. PMID- 27184653 TI - Synchronous multicentric small hepatocellular carcinomas: defining the capsule on high-frequency intraoperative ultrasonography with pathologic correlation. AB - PURPOSE: The aim of this study was to define the capsules of synchronous multicentric small hepatocellular carcinomas (HCCs) with use of high-frequency intraoperative ultrasonography (IOUS). METHODS: Among the 131 consecutive patients undergoing hepatic resection and high-frequency IOUS for HCC, 16 synchronous multicentric small HCCs in 13 patients were histologically diagnosed in the resected specimens. High-frequency IOUS and pathologic findings of these lesions were compared, with particular focus on the presence and appearance of the capsule in or around each lesion. RESULTS: Synchronous multicentric small HCCs were pathologically classified into distinctly nodular (n=12) or vaguely nodular (n=4) types. All 12 distinctly nodular HCCs including six subcentimeter lesions showed detectable capsules on high-frequency IOUS and pathology. The capsules appeared as a hypoechoic rim containing hyperechoic foci (n=6), hypoechoic rim (n=5), or hyperechoic rim (n=1) with varying degrees of coverage around each lesion. Histologically, the capsules were composed of a combination of one to four layers consisting of a fibrous capsule, peritumoral fibrosis, prominent small vessels, and entrapped hepatic parenchyma. CONCLUSION: Synchronous multicentric small HCCs with distinctly nodular type, even at subcentimeter size, can show capsules with varying coverage and diverse echogenicity on high-frequency IOUS. PMID- 27184652 TI - Malignant-looking thyroid nodules with size reduction: core needle biopsy results. AB - PURPOSE: The aim of this study was to evaluate whether malignant-looking thyroid nodules with size reduction were malignant or not. METHODS: From November 2010 to July 2011, we retrospectively enrolled 16 patients with 16 nodules (11 females and five males; mean age, 55 years) who underwent core needle biopsy (CNB), and whose thyroid nodules had malignant ultrasonographic (US) features, although they showed size reduction (>20% decrease in maximum diameter) during the follow-up period (mean, 37+/-27 months). The histologic findings of the CNB specimen were reviewed and correlated with the US findings. US studies were analyzed for their internal content, shape, margin, echogenicity, the presence of microcalcification and macrocalcification, inner isoechoic rim, and low-echoic halo. RESULTS: All nodules were confirmed as benign by CNB. Pathologic analysis was available for 12 CNB specimens. US imaging showed central hypoechogenicity or marked hypoechogenicity in all cases and a peripheral isoechoic rim in 15 nodules. US pathologic correlation showed that the central hypoechoic area was primarily composed of fibrosis (12/12) and hemorrhage (8/12) and that the isoechoic rim was composed of follicular cells. CONCLUSION: In our study, the CNB results of all of the malignant-looking thyroid nodules with size reduction were benign and were primarily composed of internal fibrosis and hemorrhage. Understanding these US and pathologic features could prevent repeated fine-needle aspiration or unnecessary diagnostic surgery. PMID- 27184655 TI - Validation of the fifth edition BI-RADS ultrasound lexicon with comparison of fourth and fifth edition diagnostic performance using video clips. AB - PURPOSE: The aim of this study was to evaluate the positive predictive value (PPV) and the diagnostic performance of the ultrasonographic descriptors in the fifth edition of BI-RADS, comparing with the fourth edition using video clips. METHODS: From September 2013 to July 2014, 80 breast masses in 74 women (mean age, 47.5+/-10.7 years) from five institutions of the Korean Society of Breast Imaging were included. Two radiologists individually reviewed the static and video images and analyzed the images according to the fourth and fifth edition of BI-RADS. The PPV of each descriptor was calculated and diagnostic performances between the fourth and fifth editions were compared. RESULTS: Of the 80 breast masses, 51 (63.8%) were benign and 29 (36.2%) were malignant. Suspicious ultrasonographic features such as irregular shape, non-parallel orientation, angular or spiculated margins, and combined posterior features showed higher PPV in both editions (all P<0.05). No significant differences were found in the diagnostic performances between the two editions (all P>0.05). The area under the receiver operating characteristics curve was higher in the fourth edition (0.708 to 0.690), without significance (P=0.416). CONCLUSION: The fifth edition of the BI-RADS ultrasound lexicon showed comparable performance to the fourth edition and can be useful in the differential diagnosis of breast masses using ultrasonography. PMID- 27184654 TI - Measurement of elasticity of normal placenta using the Virtual Touch quantification technique. AB - PURPOSE: The aim of this study was to measure the elasticity of normal placentas using the Virtual Touch quantification (VTQ) technique. METHODS: This study was approved by the Institutional Ethics Committee. Fifty randomly selected, healthy pregnant women in their second trimester and 50 randomly selected, healthy pregnant women in their third trimester with a single fetus were included, and their placentas underwent VTQ through shear wave velocity (SWV) measurements. The measurements were performed at different locations to sample different areas of the placenta. Measurements were performed 3-4 times in each location, the mean shear wave velocities were calculated without the highest and lowest values of measurements in each region, and the results were compared. RESULTS: The SWV of the placenta was 0.983+/-0.260 m/sec, and the minimal and maximal speed was 0.63 m/sec and 1.84 m/sec, respectively. There was no significant difference between the second and third trimester of VTQ of the placenta in terms of SWV (0.978+/ 0.255 m/sec vs. 0.987+/-0.266 m/sec, P=0.711). The maternal age between second and third trimester was 27.9+/-4.3 years and 29.2+/-4.4 years, respectively; there was no significant difference between them (P=0.159). CONCLUSION: The results of this study show that the SWV of normal placenta tissue is 0.983+/ 0.260 m/sec, it has little variation between the second and third trimesters, and the VTQ technique may potentially play an additional role in placenta evaluation. PMID- 27184656 TI - Clinical application of S-Detect to breast masses on ultrasonography: a study evaluating the diagnostic performance and agreement with a dedicated breast radiologist. AB - PURPOSE: The purpose of this study was to evaluate the diagnostic performance of S-Detect when applied to breast ultrasonography (US), and the agreement with an experienced radiologist specializing in breast imaging. METHODS: From June to August 2015, 192 breast masses in 175 women were included. US features of the breast masses were retrospectively analyzed by a radiologist who specializes in breast imaging and S-Detect, according to the fourth edition of the American College of Radiology Breast Imaging Reporting and Data System lexicon and final assessment categories. Final assessments from S-Detect were in dichotomized form: possibly benign and possibly malignant. Kappa statistics were used to analyze the agreement between the radiologist and S-Detect. Diagnostic performance of the radiologist and S-Detect was calculated, including sensitivity, specificity, positive predictive value (PPV), negative predictive value, accuracy, and area under the receiving operator characteristics curve. RESULTS: Of the 192 breast masses, 72 (37.5%) were malignant, and 120 (62.5%) were benign. Benign masses among category 4a had higher rates of possibly benign assessment on S-Detect for the radiologist, 63.5% to 36.5%, respectively (P=0.797). When the cutoff was set at category 4a, the specificity, PPV, and accuracy was significantly higher in S Detect compared to the radiologist (all P<0.05), with a higher area under the receiver operator characteristics curve of 0.725 compared to 0.653 (P=0.038). Moderate agreement (k=0.58) was seen in the final assessment between the radiologist and S-Detect. CONCLUSION: S-Detect may be used as an additional diagnostic tool to improve the specificity of breast US in clinical practice, and guide in decision making for breast masses detected on US. PMID- 27184657 TI - Exosomal Long Noncoding RNAs are Differentially Expressed in the Cervicovaginal Lavage Samples of Cervical Cancer Patients. AB - BACKGROUND: As the second leading cause of cancer morbidity and death in women, cervical cancer remains an important public health problem worldwide. Novel biomarkers with high sensitivity and specificity for the early detection and diagnosis of cervical cancer are urgently needed. Increasing evidence shows that long noncoding RNAs (lncRNAs) are differentially expressed in cancer tissues and may serve as diagnostic markers. In multiple tumor types, exosomes harboring lncRNAs are actively released from tumor cells. In this study, we investigate the potential association of exosomal lncRNA expression with cervical cancer. METHODS: Cervicovaginal lavage specimens were collected from patients with cervical cancer and cancer-free volunteers who are HPV-positive or HPV-negative. Exosomes in these specimens were isolated by ultracentrifugation and confirmed by transmission electron microscopy. The exosomal lncRNAs HOTAIR, MALAT1, and MEG3 were quantified by qRT-PCR. RESULTS: Expression of HOTAIR, MALAT1 and MEG3 was predominantly observed in cervical cancer-derived exosomes in cervicovaginal lavage samples. The expression levels of lncRNAs were significantly different in exosomes isolated from cervical cancer patients compared to normal controls. CONCLUSIONS: Our data suggest that lncRNAs in exosomes isolated from cervicovaginal lavage are differentially expressed in cervical cancer patients and cancer-free volunteers. Exosomal lncRNAs may have great potential to be used for the early detection and diagnosis of cervical cancer, and serve as convenient and noninvasive biomarkers. PMID- 27184658 TI - Development of a quantitative validation method for forensic investigation of human spermatozoa using a commercial fluorescence staining kit (SPERM HY-LITERTM Express). AB - In investigations of sexual assaults, as well as in identifying a suspect, the detection of human sperm is important. Recently, a kit for fluorescent staining of human spermatozoa, SPERM HY-LITERTM, has become available. This kit allows for microscopic observation of the heads of human sperm using an antibody tagged with a fluorescent dye. This kit is specific to human sperm and provides easy detection by luminescence. However, criteria need to be established to objectively evaluate the fluorescent signals and to evaluate the staining efficiency of this kit. These criteria will be indispensable for investigation of forensic samples. In the present study, the SPERM HY-LITERTM Express kit, which is an improved version of SPERM HY-LITERTM, was evaluated using an image analysis procedure using Laplacian and Gaussian methods. This method could be used to automatically select important regions of fluorescence produced by sperm. The fluorescence staining performance was evaluated and compared under various experimental conditions, such as for aged traces and in combination with other chemical staining methods. The morphological characteristics of human sperm were incorporated into the criteria for objective identification of sperm, based on quantified features of the fluorescent spots. Using the criteria, non-specific or insignificant fluorescent spots were excluded, and the specificity of the kit for human sperm was confirmed. The image analysis method and criteria established in this study are universal and could be applied under any experimental conditions. These criteria will increase the reliability of operator judgment in the analysis of human sperm samples in forensics. PMID- 27184659 TI - Dityrosine as a marker of acute myocardial infarction? Experiments with the isolated Langendorff heart. AB - The isolated Langendorff heart was used to evaluate dityrosine as a marker of acute myocardial infarctions. The animal model allowed the generation of local infarctions with defined survival times, as well as infarctions with and without reperfusion. The results showed that dityrosine, at least under the conditions of the animal model, occurs very shortly after early ischemia and infarctions, since positive staining results were already obtained after a survival time of only 5 min. Furthermore, it could be proved that the occurrence of dityrosine does not depend on a reperfusion of the ischemic muscle area and that there are no differences in the staining patterns of infarctions with and without reperfusion. Positive staining results for dityrosine in control hearts without infarctions had to be considered when evaluating the tissue samples of the study hearts. In part, the positive staining results of the control hearts seemed to be an artefact of the Langendorff system, easily identifiable by a distinctive staining pattern. Positive staining results in tissue samples of hearts that suffered from arrhythmia on the other hand implied that the occurrence of dityrosine is not specific for myocardial infarctions. Taking into account the results of previous works on human tissue samples, however, these findings did not question the use of dityrosine as a diagnostic tool; they simply showed that myocardial damage due to oxidative stress might occur under various pathologic conditions. PMID- 27184660 TI - A 17-month time course study of human RNA and DNA degradation in body fluids under dry and humid environmental conditions. AB - Blood, saliva, and semen are some of the forensically most relevant biological stains commonly found at crime scenes, which can often be of small size or challenging due to advanced decay. In this context, it is of great importance to possess reliable knowledge about the effects of degradation under different environmental conditions and to use appropriate methods for retrieving maximal information from limited sample amount. In the last decade, RNA analysis has been demonstrated to be a reliable approach identifying the cell or tissue type of an evidentiary body fluid trace. Hence, messenger RNA (mRNA) profiling is going to be implemented into forensic casework to supplement the routinely performed short tandem repeat (STR) analysis, and therefore, the ability to co-isolate RNA and DNA from the same sample is a prerequisite. The objective of this work was to monitor and compare the degradation process of both nucleic acids for human blood, saliva, and semen stains at three different concentrations, exposed to dry and humid conditions during a 17-month time period. This study also addressed the question whether there are relevant differences in the efficiency of automated, magnetic bead-based single DNA or RNA extraction methods compared to a manually performed co-extraction method using silica columns. Our data show that mRNA, especially from blood and semen, can be recovered over the entire time period surveyed without compromising the success of DNA profiling; mRNA analysis indicates to be a robust and reliable technique to identify the biological source of aged stain material. The co-extraction method appears to provide mRNA and DNA of sufficient quantity and quality for all different forensic investigation procedures. Humidity and accompanied mold formation are detrimental to both nucleic acids. PMID- 27184662 TI - Smoothelin and WT-1 expression in glomus tumors and glomuvenous malformations. AB - BACKGROUND: Smoothelin is a specific marker for smooth muscle cells with contractile capacity which has not been widely studied in glomus lesions. In the same way, the expression for Wilms tumor 1 (WT1) has only been studied occasionally in the endothelial cells of glomovenous malformations and in the glomus cells of glomus tumours. OBJECTIVE: We studied the significance of immunohistochemical expression of smoothelin and WT1 in 25 glomus lesions. METHODS: We assessed 9 cases of solid glomus tumors (SGT), 8 cases of glomus tumors with vascular ectasia (VEGT), 2 cases of glomangiomyomas (GMM) and 6 cases of glomuvenous malformation (GM). Immunohistochemistry was performed, evaluating the expression of WT1, smoothelin, smooth muscle actin (SMA), smooth muscle myosin (SMM), h-caldesmon and desmin. RESULTS: Glomic cells showed cytoplasmic positivity for smoothelin, and WT1 expression was present in all studied cases. SGT showed WT1 positivity in all endothelia. However, in regarding VEGT and GMM, WT1 endothelial expression was positive in some areas, but not in others. GM did not show endothelial cell positivity for WT1. CONCLUSIONS: Smoothelin expression in glomic cells indicates that they are contractile smooth muscle cells, and thus its role in routine diagnosis should be considered. The absence of WT1 expression in the endothelium of the vascular structures of the GM is a differential characteristic between SGT, VEGT and GMM. PMID- 27184661 TI - A systematic review of community based hepatitis C treatment. AB - BACKGROUND: Hepatitis C virus (HCV) treatment uptake globally is low. A barrier to treatment is the necessity to attend specialists, usually in a tertiary hospital. We investigate the literature to assess the effect of providing HCV treatment in the community on treatment uptake and cure. METHODS: Three databases were searched for studies that contained a comparison between HCV treatment uptake or sustained virologic response (SVR) in a community site and a tertiary site. Treatment was with standard interferon with or without ribavirin, or pegylated interferon and ribavirin. A narrative synthesis was conducted. RESULTS: Thirteen studies fulfilled the inclusion criteria. Six studies measured treatment uptake; three demonstrated an increase in uptake at the community site, two demonstrated similar rates between sites and one demonstrated decreased uptake at the community site. Nine studies measured SVR; four demonstrated higher SVR rates in the community, four demonstrated similar SVR rates, and one demonstrated inferior SVR rates in the community compared to the tertiary site. CONCLUSION: The data available supports the efficacy of HCV treatment in the community, and the potential for community based treatment to increase treatment uptake. Whilst further studies are required, these findings highlight the potential benefit of providing community based HCV care - benefits that should be realised as interferon-free therapy become available. (PROSPERO registration number CRD42015025505). PMID- 27184663 TI - Construction of Cyclic Sulfamidates Bearing Two gem-Diaryl Stereocenters through a Rhodium-Catalyzed Stepwise Asymmetric Arylation Protocol. AB - A rhodium-catalyzed stepwise asymmetric 1,4- and 1,2-addition of arylboronic acids to alpha,beta-unsaturated cyclic N-sulfonyl ketimines has been developed, providing a wide range of gem-diaryl-substituted chiral benzosulfamidates with high optical purities. C1-Symmetric chiral diene and branched chiral sulfur olefin ligands were sequentially utilized in this double-arylation process for high stereocontrol. Further synthetic utility offers new opportunities for the facile construction of otherwise difficult to access polycyclic heterocycles. PMID- 27184664 TI - Effect of the Cardio First AngelTM device on CPR indices: a randomized controlled clinical trial. AB - BACKGROUND: A number of cardiopulmonary resuscitation (CPR) adjunct devices have been developed to improve the consistency and quality of manual chest compressions. We investigated whether a CPR feedback device would improve CPR quality and consistency, as well as patient survival. METHODS: We conducted a randomized controlled study of patients undergoing CPR for cardiac arrest in the mixed medical-surgical intensive care units of four academic teaching hospitals. Patients were randomized to receive either standard manual CPR or CPR using the Cardio First AngelTM CPR feedback device. Recorded variables included guideline adherence, CPR quality, return of spontaneous circulation (ROSC) rates, and CPR associated morbidity. RESULTS: A total of 229 subjects were randomized; 149 were excluded; and 80 were included. Patient demographics were similar. Adherence to published CPR guidelines and CPR quality was significantly improved in the intervention group (p < 0.0001), as were ROSC rates (72 % vs. 35 %; p = 0.001). A significant decrease was observed in rib fractures (57 % vs. 85 %; p = 0.02), but not sternum fractures (5 % vs. 17 %; p = 0.15). CONCLUSIONS: Use of the Cardio First AngelTM CPR feedback device improved adherence to published CPR guidelines and CPR quality, and it was associated with increased rates of ROSC. A decrease in rib but not sternum fractures was observed with device use. Further independent prospective validation is warranted to determine if these results are reproducible in other acute care settings. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02394977 . Registered on 5 Mar 2015. PMID- 27184666 TI - Caudatin induces caspase-dependent apoptosis in human glioma cells with involvement of mitochondrial dysfunction and reactive oxygen species generation. AB - Caudatin as one species of C-21 steroidal from Cynanchum bungei decne displays potential anticancer activity. However, the underlying mechanisms remain elusive. In the present study, the growth suppressive effect and mechanism of caudatin on human glioma U251 and U87 cells were evaluated in vitro. The results indicated that caudatin significantly inhibited U251 and U87 cell growth in both a time- and dose-dependent manner. Flow cytometry analysis revealed that caudatin-induced cell growth inhibition was achieved by induction of cell apoptosis, as convinced by the increase of Sub-G1 peak, PARP cleavage and activation of caspase-3, caspase-7 and caspase-9. Caudatin treatment also resulted in mitochondrial dysfunction which correlated with an imbalance of Bcl-2 family members. Further investigation revealed that caudatin triggered U251 cell apoptosis by inducing reactive oxygen species (ROS) generation through disturbing the redox homeostasis. Moreover, pretreatment of caspase inhibitors apparently weakens caudatin-induced cell killing, PARP cleavage and caspase activation and eventually reverses caudatin-mediated apoptosis. Importantly, caudatin significantly inhibited U251 tumour xenografts in vivo through induction of cell apoptosis involving the inhibition of cell proliferation and angiogenesis, which further validate its value in combating human glioma in vivo. Taken together, the results described above all suggest that caudatin inhibited human glioma cell growth by induction of caspase-dependent apoptosis with involvement of mitochondrial dysfunction and ROS generation. PMID- 27184665 TI - Efficacy and safety of fluconazole prophylaxis in extremely low birth weight infants: multicenter pre-post cohort study. AB - BACKGROUND: There have been many studies supporting fluconazole prophylaxis in preterm infants for prevention of invasive fungal infections (IFIs). However, the routine use of fluconazole prophylaxis in neonatal intensive care units (NICUs) raises concerns with respect to resistance development, including the selection of resistant Candida species. We aimed to evaluate the efficacy and safety of fluconazole prophylaxis in extremely low birth weight (ELBW) infants. METHODS: An interventional pre-post cohort study at two tertiary NICUs was conducted. Data from two 5-year periods with and without fluconazole prophylaxis (Mar 2008-Feb 2013 and Mar 2003-Feb 2008) was compared. Prophylactic fluconazole was administered starting on the 3rd day at a dose of 3 mg/kg twice a week for 4 weeks during the prophylaxis period. RESULTS: The fluconazole prophylaxis group consisted of 264 infants, and the non-prophylaxis group consisted of 159 infants. IFI occurred in a total of 19 neonates (4.7 %) during the 10-year study period. Fluconazole prophylaxis lower the fungal colonization rate significantly (59.1 % vs. 33.9 %, P <0.001). However, the incidence of IFIs in ELBW infants was not reduced after fluconazole prophylaxis (4.4 % vs. 5.5 %, P = 0.80). Rather, although the increase did not reach statistical significance, fluconazole prophylaxis tended to increase the incidence of invasive infections involving fluconazole-resistant C. parapsilosis (0 % vs. 41.7 %, P = 0.11). CONCLUSIONS: Fluconazole prophylaxis was not efficacious in decreasing IFIs in ELBW infants. There is a need for targeting prophylaxis to greatest risk population and prospective studies to measure the long-term effect of fluconazole prophylaxis on the emergence of organisms with antifungal resistance. PMID- 27184667 TI - Cytotoxicity, intracellular localization and exocytosis of citrate capped and PEG functionalized gold nanoparticles in human hepatocyte and kidney cells. AB - Surface-modified gold nanoparticles (AuNPs) are nanomaterials that hold promise in drug delivery applications. In this study, the cytotoxicity, uptake, intracellular localization, and the exocytosis of citrate-stabilized (Cit-AuNP) and polyethylene glycol (PEG)-modified gold nanoparticles with the carboxyl (COOH) terminal functional group were assessed in human embryonic kidney (HEK 293) and the human caucasian hepatocytes carcinoma (Hep G2) cell systems, representing two major accumulation sites for AuNPs. The zeta (zeta)-potential measurements confirmed the negative surface charge of the AuNPs in water and in cell growth medium. The transmission electron microscopy confirmed the size and morphology of the AuNPs. Both types of AuNPs were shown to induce cytotoxic effects in cells. The Hep G2 cells were more sensitive cell type, with the COOH PEG-AuNPs inducing the highest toxicity at higher concentrations. Dark field microscopy and TEM images revealed that the AuNPs were internalized in cells, mostly as agglomerates. TEM micrographs further revealed that the AuNPs were confined as agglomerates inside vesicle-like compartments, likely to be endosomal and lysosomal structures as well as in the cytosol, mostly as individual particles. The AuNPs were shown to remain in cellular compartments for up to 3 weeks, but thereafter, clearance of the gold nanoparticles from the cells by exocytosis was evident. The results presented in this study may therefore give an indication on the fate of AuNPs on long-term exposure to cells and may also assist in safety evaluation of AuNPs. PMID- 27184669 TI - Improvement of the Thermal Stability of TEMPO-Oxidized Cellulose Nanofibrils by Heat-Induced Conversion of Ionic Bonds to Amide Bonds. AB - Improving thermal stability of TEMPO-oxidized cellulose nanofibrils (TOCNs) is a major challenge for the development and preparation of new nanocomposites. However, thermal degradation of TOCNs occurs at 220 degrees C. The present study reports a simple way to improve thermal stability of TOCNs by the heat-induced conversion of ionic bonds to amide bonds. Coupling amine-terminated polyethylene glycol to the TOCNs is performed through ionic bond formation. Films are produced from the dispersions by the casting method. Infrared spectroscopy and thermogravimetric analysis confirm conversion of ionic bonds to amide bonds for the modified TOCN samples after heating. As a result, improvement of TOCNs' thermal stability by up to 90 degrees C is successfully achieved. PMID- 27184668 TI - Mesd extrinsically promotes phagocytosis by retinal pigment epithelial cells. AB - Phagocytosis is a critical process to maintain tissue homeostasis. In the retina, photoreceptor cells renew their photoexcitability by shedding photoreceptor outer segments (POSs) in a diurnal rhythm. Shed POSs are phagocytosed by retinal pigment epithelial (RPE) cells to prevent debris accumulation, retinal degeneration, and blindness. Phagocytosis ligands are the key to understanding how RPE recognizes shed POSs. Here, we characterized mesoderm development candidate 2 (Mesd or Mesdc2), an endoplasmic reticulum (ER) chaperon for low density lipoprotein receptor-related proteins (LRPs), to extrinsically promote RPE phagocytosis. The results showed that Mesd stimulated phagocytosis of fluorescence-labeled POS vesicles by D407 RPE cells. Ingested POSs were partially degraded within 3 h in some RPE cells to dispense undegradable fluorophore throughout the cytoplasm. Internalized POSs were colocalized with phagosome biomarker Rab7, suggesting that Mesd-mediated engulfment is involved in a phagocytosis pathway. Mesd also facilitated phagocytosis of POSs by primary RPE cells. Mesd bound to unknown phagocytic receptor(s) on RPE cells. Mesd was detected in the cytoplasm, but not nuclei, of different retinal layers and is predominantly expressed in the ER-free cellular compartment of POSs. Mesd was not secreted into medium from healthy cells but passively released from apoptotic cells with increased membrane permeability. Released Mesd selectively bound to the surface of POS vesicles and apoptotic cells, but not healthy cells. These results suggest that Mesd may be released from and bind to shed POSs to facilitate their phagocytic clearance. PMID- 27184670 TI - Rhodiola crenulata extract regulates hepatic glycogen and lipid metabolism via activation of the AMPK pathway. AB - BACKGROUND: Metabolic syndrome may lead to many complications, such as nonalcoholic fatty liver disease (NAFLD). A natural and effective therapeutic agent for patients with NAFLD is urgently needed. In a previous study, we showed that Rhodiola crenulata root extract (RCE) regulated hepatic gluconeogenesis through activation of AMPK signaling. However, the manner in which RCE regulates hepatic lipid and glycogen metabolism remains unclear. The current study was conducted to investigate the effects of RCE on hepatic glycogen and lipid metabolism, as well as the mechanisms underlying such effects. METHODS: Human hepatoma HepG2 cells were treated with RCE for 6 h under high glucose conditions, after which glycogen synthesis, lipogenesis, and relative gene expression were examined. In addition, lipogenesis-related genes were investigated in vivo. RESULTS: RCE significantly increased glycogen synthesis and inhibited lipogenesis, while regulating genes related to these processes, including glycogen synthase kinase 3beta (GSK3beta), glycogen synthase (GS), fatty acid synthase (FAS), CCAAT/enhancer-binding protein (C/EBP), and sterol regulatory element-binding protein 1c (SREBP-1c). However, the effects caused by RCE were neutralized by compound C, an AMPK antagonist. Further studies showed that expression levels of lipogenic genes decreased at the protein and mRNA levels in the rat liver. CONCLUSIONS: Our results demonstrate that RCE regulates hepatic glycogen and lipid metabolism through the AMPK signaling pathway. These results suggest that RCE is a potential intervention for patients with NAFLD. PMID- 27184671 TI - Xylitol production from waste xylose mother liquor containing miscellaneous sugars and inhibitors: one-pot biotransformation by Candida tropicalis and recombinant Bacillus subtilis. AB - BACKGROUND: The process of industrial xylitol production is a massive source of organic pollutants, such as waste xylose mother liquor (WXML), a viscous reddish brown liquid. Currently, WXML is difficult to reuse due to its miscellaneous low cost sugars, high content of inhibitors and complex composition. WXML, as an organic pollutant of hemicellulosic hydrolysates, accumulates and has become an issue of industrial concern in China. Previous studies have focused only on the catalysis of xylose in the hydrolysates into xylitol using one strain, without considering the removal of other miscellaneous sugars, thus creating an obstacle to subsequent large-scale purification. In the present study, we aimed to develop a simple one-pot biotransformation to produce high-purity xylitol from WXML to improve its economic value. RESULTS: In the present study, we developed a procedure to produce xylitol from WXML, which combines detoxification, biotransformation and removal of by-product sugars (purification) in one bioreactor using two complementary strains, Candida tropicalis X828 and Bacillus subtilis Bs12. At the first stage of micro-aerobic biotransformation, the yeast cells were allowed to grow and metabolized glucose and the inhibitors furfural and hydroxymethyl furfural (HMF), and converted xylose into xylitol. At the second stage of aerobic biotransformation, B. subtilis Bs12 was activated and depleted the by-product sugars. The one-pot process was successfully scaled up from shake flasks to 5, 150 L and 30 m(3) bioreactors. Approximately 95 g/L of pure xylitol could be obtained from the medium containing 400 g/L of WXML at a yield of 0.75 g/g xylose consumed, and the by-product sugars glucose, L-arabinose and galactose were depleted simultaneously. CONCLUSIONS: Our results demonstrate that the one-pot procedure is a viable option for the industrial application of WXML to produce value-added chemicals. The integration of complementary strains in the biotransformation of hemicellulosic hydrolysates is efficient under optimized conditions. Moreover, our study of one-pot biotransformation also provides useful information on the combination of biotechnological processes for the biotransformation of other compounds. PMID- 27184673 TI - Abdominal Wall Schwannoma. AB - Neurilemmomas-or schwannomas-are rare soft tissue tumours involving peripheral nerve sheaths, usually found in the head and neck regions. They can infrequently originate within the tissues of the abdominal wall. Here, we present a case of symptomatic schwannoma of the abdominal wall in a 62-year-old woman referred for abdominal pain in the right iliac fossa. On physical examination, a 5-7-cm oval shaped area of consolidation with regular borders and elastic consistence was palpable. Ultrasound examination of the abdomen revealed a hypoechogenic mass measuring 80-33-42 mm; subsequently, a CT scan confirmed the presence of a well circumscribed mass, with small calcifications inside. Radical excision of the lesion under general anaesthesia was performed, and the histological examination was consistent with the diagnosis of "ancient" schwannoma. The patient was discharged on the second postoperative day, and, at a clinical check 1 month postoperation, she reported no recurrence of abdominal pain and had an improved quality of life. Schwannomas have a good prognosis overall, with malignant degeneration being very rare. Local recurrence is plausible only if non-radical resection of the primitive tumour occurs. This is the second case ever reported, to our knowledge, of symptomatic schwannoma of the abdominal wall. We advocate surgical removal of the tumour when it presents as a cause of abdominal pain, ensuring that a radical excision is performed due to the possibility-though rare of malignant transformation or recurrence. This offers the possibility of total regression of symptoms through surgical therapy. PMID- 27184674 TI - Buried Barrett's Esophagus-a Sheep in Sheep's Clothing. PMID- 27184672 TI - Determinants of Outcomes Following Resection for Pancreatic Cancer-a Population Based Study. AB - BACKGROUND: Patient and health system determinants of outcomes following pancreatic cancer resection, particularly the relative importance of hospital and surgeon volume, are unclear. Our objective was to identify patient, tumour and health service factors related to mortality and survival amongst a cohort of patients who underwent completed resection for pancreatic cancer. METHODS: Eligible patients were diagnosed with pancreatic adenocarcinoma between July 2009 and June 2011 and had a completed resection performed in Queensland or New South Wales, Australia, with either tumour-free (R0) or microscopically involved margins (R1) (n = 270). Associations were examined using logistic regression (for binary outcomes) and Cox proportional hazards or stratified Cox models (for time to-event outcomes). RESULTS: Patients treated by surgeons who performed <4 resections/year were more likely to die from a surgical complication (versus >=4 resections/year, P = 0.04), had higher 1-year mortality (P = 0.03), and worse overall survival up to 1.5 years after surgery (adjusted hazard ratio 1.58, 95 % confidence interval 1.07-2.34). Amongst patients who had >=1 complication within 30 days of surgery, those aged >=70 years had higher 1-year mortality compared to patients aged <60 years. Adjuvant chemotherapy treatment improved recurrence-free survival (P = 0.01). There were no significant associations between hospital volume and mortality or survival. CONCLUSIONS: Systems should be implemented to ensure that surgeons are completing a sufficient number of resections to optimize patient outcomes. These findings may be particularly relevant for countries with a relatively small and geographically dispersed population. PMID- 27184676 TI - Psychiatric and Behavioural Disorders in Children with Epilepsy (ILAE Task Force Report): Behavioural and psychiatric disorders associated with childhood epilepsy syndromes. AB - The categorisation of the childhood epilepsies into a number of different syndromes has allowed greater insight into the prognosis, not only with regard to seizure control but also in relation to cognitive and behavioural outcome. The role of genetics in determining both the syndrome and the behavioural outcome remains promising, although the promise is still largely unfulfilled. The behavioural/psychiatric outcome of a selection of the large number of childhood epilepsy syndromes is presented. The rate of autism in West syndrome, particularly in children who have tuberous sclerosis with temporal tubers, is high. In Dravet syndrome there is a loss of skills, with an associated increase in behavioural problems. The frequency of both subtle and overt seizures in the Lennox-Gastaut syndrome almost certainly accounts for the apparent poor motivation; however, a marked improvement in seizure control with treatment can also result in behavioural problems, probably as a result of the "release phenomenon". A number of cognitive problems can arise in the so-called "benign" syndrome of epilepsy with centrotemporal spikes (BECTS) and the rate of ADHD is high. Autistic features and ADHD have been described in the Landau-Kleffner syndrome and other syndromes associated with electrical status epilepticus of slow-wave sleep (ESES). Early effective treatment may reverse some of these features. There is clear evidence for a behavioural syndrome in relation to juvenile myoclonic epilepsy (JME), in which both clinical descriptions and functional neuroimaging indicate frontal lobe deficits. PMID- 27184675 TI - Laparoscopic Total Gastrectomy with D2 Lymphadenectomy and Side-to-Side Stapled Esophagojejunostomy. AB - INTRODUCTION: An optimal method has yet to be established for laparoscopic total gastrectomy with intracorporeal anastomosis. METHODS: We aim to describe a simple technique for intracorporeal anastomoses. Technique of laparoscopic total gastrectomy with side-to-side stapled intracorporeal esophagojejunostomy anastomosis and Roux-en-Y jejunojejunostomy is performed on patients with gastric malignancy in an academic community tertiary care center. RESULTS: The anastomotic technique of laparoscopic total gastrectomy with side-to-side stapled esophagojejunostomy is described. CONCLUSION: Laparoscopic total gastrectomy with D2 lymphadenectomy and side-to-side esophagojejunostomy is safe to perform and has the advantage of a wide lumen with low chance for stricture. A laparoscopic total gastrectomy with stapled side-to-side esophagojejunostomy is feasible and safe in advanced gastric cancer. PMID- 27184678 TI - Iron deficiency anaemia in pregnancy: The role of parenteral iron. AB - Maternal and perinatal morbidity and mortality remain major challenges in the delivery of safe maternity care worldwide. Anaemia in pregnancy is an important contributor to this dismal picture, especially where blood transfusion services are poorly developed. An early diagnosis and treatment of iron deficiency anaemia in pregnancy using the new generation dextran-free parenteral iron preparations can save lives and reduce morbidity in selected pregnancies. It is time to cast aside the fears associated with the use of the old parenteral iron preparations which were associated a high incidence of anaphylaxis, and embrace the use of new parenteral iron products which have better side effect profiles and can deliver total dose infusions without the need for test dosing. In selected women, the benefits of this treatment far outweigh any disadvantages. PMID- 27184677 TI - In Vivo Evaluation of a PEO-Gellan Gum Semi-Interpenetrating Polymer Network for the Oral Delivery of Sulpiride. AB - In this study, an optimized epichlorohydrin-crosslinked semi-interpenetrating polymer network xerogel matrix system (XePoMas) for the controlled delivery of sulpiride was prepared. The ability of XePoMas to sustain drug release was determined by in vitro and in vivo drug release experiments. Swelling of the xerogel over the 24-h experimental period ranged from 346 to 648%; swelling was observed to increase exponentially over the initial 8 h. In vitro drug release depicted a linear zero order drug release profile with an R 2 value of 0.9956. The ability of the fabricated XePoMas to sustain drug release and enhance bioavailability of sulpiride in vivo was investigated by evaluating the plasma drug concentration over 24 h in the large pig model. The optimized XePoMas formulation was shown to increase intestinal absorption of sulpiride to a greater extent than the marketed product in vivo, with a C max of 830.58 ng/mL after 15 h. PMID- 27184686 TI - Liver Allograft Provides Immunoprotection for the Cardiac Allograft in Combined Heart-Liver Transplantation. AB - When transplanted simultaneously, the liver allograft has been thought to have an immunoprotective role on other organs; however, detailed analyses in simultaneous heart-liver transplantation (SHLT) have not been done to date. We analyzed patient outcomes and incidence of immune-mediated injury in 22 consecutive SHLT versus 223 isolated heart transplantation (IHT) recipients between January 2004 and December 2013, by reviewing 3912 protocol- and indication-specific cardiac allograft biopsy specimens. Overall survival was similar (86.4%, 86.4%, and 69.1% for SHLT and 93.3%, 84.7%, and 70.0% for IHT at 1, 5, and 10 years; p = 0.83). Despite similar immunosuppression, the incidence of T cell-mediated rejection (TCMR) was lower in SHLT (31.8%) than in IHT (84.8%) (p < 0.0001). Although more SHLT patients had preexisting donor-specific HLA antibody (22.7% versus 8.1%; p = 0.04), the incidence of antibody-mediated rejection was not different in SHLT compared with IHT (4.5% versus 14.8%, p = 0.33). While the left ventricular ejection fraction was comparable in both groups at 5 years, the incidence and severity of cardiac allograft vasculopathy were reduced in the SHLT recipients (42.9% versus 66.8%, p = 0.03). Simultaneously transplanted liver allograft was associated with reduced risk of TCMR (odds ratio [OR] 0.003, 95% confidence interval [CI] 0-0.02; p < 0.0001), antibody-mediated rejection (OR 0.04, 95% CI 0 0.46; p = 0.004), and cardiac allograft vasculopathy (OR 0.26, 95% CI 0.07-0.84; p = 0.02), after adjusting for other risk factors. These data suggest that the incidence of alloimmune injury in the heart allograft is reduced in SHLT recipients. PMID- 27184688 TI - Fulminant hepatitis B virus reactivation following antiviral treatment interruption in a chronically infected patient. PMID- 27184687 TI - Mild hyperglycemia triggered islet function recovery in streptozotocin-induced insulin-deficient diabetic rats. AB - AIMS/INTRODUCTION: Moderate elevation of glucose level has been shown to effectively promote beta-cell replication in various models in vitro and in normal rodents. Here, we aimed to test the effect of moderately elevated glucose on beta-cell mass expansion and islet function recovery in diabetic animal models. MATERIALS AND METHODS: A single high dose of streptozotocin was given to induce insulin-deficient diabetes in adult male Sprague-Dawley rats. Then, 48 h after streptozotocin injection, newly diabetic rats were randomly divided into three groups: (i) no treatment to maintain hyperglycemia; (ii) daily exogenous long-acting human insulin analog injection that maintained mild hyperglycemia (15 mmol/L < blood glucose < 18 mmol/L); (iii) daily exogenous long-acting human insulin analog injection to restore normoglycemia (blood glucose <8 mmol/L) as a control. Islet function, beta-cell regeneration and beta-cell replication were monitored during the entire analysis period. RESULTS: A single high dose of streptozotocin induced massive loss of beta-cells, resulting in irreversible hyperglycemia. Mild hyperglycemia markedly promoted beta-cell proliferation, leading to robust beta-cell regeneration. Importantly, rats that maintained mild hyperglycemia showed nearly normal glucose-stimulated insulin secretion, glucose disposal and random blood glucose levels, suggesting almost full restoration of the islet function. Normalization of blood glucose levels profoundly blunted beta cell replication, regeneration and islet function recovery observed in mild hyperglycemia. CONCLUSIONS: Our research provides a feasible approach to stimulate in situ beta-cell regeneration in diabetic rats, offering new perspectives for diabetes therapy. PMID- 27184689 TI - Severely regurgitant left ventricle to ascending aorta conduit in a failing fontan patient treated with a vascular endograft and melody transcatheter pulmonary valve via hybrid approach. AB - A 28-year-old male with single ventricular heart disease status post Fontan palliation and subsequent placement of left ventricle to ascending aorta (LV-AAo) valved conduit developed ascites and edema. Diagnostic catheterization revealed elevated ventricular end diastolic pressures (EDP) secondary to severe LV-AAo conduit regurgitation. Given the unique anatomy, surgical access via the right axillary artery provided optimal route for transcatheter valve implantation within the conduit. The procedure resulted in significant hemodynamic improvement with no complications. (c) 2016 Wiley Periodicals, Inc. PMID- 27184692 TI - Pendular Nystagmus Associated With Cerebral Pylomixoid Astrocytoma. PMID- 27184690 TI - Adjuvant Liraglutide and Insulin Versus Insulin Monotherapy in the Closed-Loop System in Type 1 Diabetes: A Randomized Open-Labeled Crossover Design Trial. AB - BACKGROUND: The closed-loop (CL) system delivers insulin in a glucose-responsive manner and optimal postprandial glycemic control is difficult to achieve with the algorithm and insulin available. We hypothesized that adjunctive therapy with liraglutide, a once-daily glucagon-like peptide-1 agonist, would be more effective in normalizing postprandial hyperglycemia versus insulin monotherapy in the CL system, in patients with type 1 diabetes. METHODS: This was a randomized, controlled, open-label, crossover design trial comparing insulin monotherapy versus adjuvant subcutaneous liraglutide 1.2 mg and insulin, using the CL system in 15 patients. Blood glucose (BG), insulin, and glucagon concentrations were analyzed. RESULTS: The liraglutide arm was associated with overall decreased mean BG levels (P = .0002). The average BG levels from 8:00 pm (day 1) to 9:00 pm (day 2) were lower in the liraglutide arm (144.6 +/- 36.31 vs 159.7 +/- 50.88 mg/dl respectively; P = .0002). Two-hour postbreakfast and lunch BG profiles were better in the liraglutide arm (P < .05) and the insulin and glucagon assay values were lower (P < .0001). Postprandially, the area under the curve (AUC) for 2-hour postbreakfast and lunch BG levels were significant (P = .01, P = .03) and the AUC for glucagon, postbreakfast (P < .0001) and lunch (P < .05), was also significant. The incidence of hypoglycemia did not differ between arms (P = .83, Fisher's exact test). Overall, adjunct liraglutide therapy plus CL was well tolerated even with expected side effects. CONCLUSION: This is a proof-of-concept study showing liraglutide can be a potential adjunctive therapy in addition to CL with insulin to reduce postprandial hyperglycemia in type 1 diabetes. PMID- 27184693 TI - Phytocannabinoids and Cannabimimetic Drugs: Recent Patents in Central Nervous System Disorders. AB - BACKGROUND: Starting from the chemical structure of phytocannabinoids, isolated from Cannabis sativa plant, research groups designed numerous cannabimimetic drugs. These compounds according to their activities can be partial, full agonists and antagonists of cannabinoid receptors. Anecdotal reports and scientific studies described beneficial properties of cannabinoids and their derivatives in several pathological conditions like neurological and neuropsychiatric disorders, and in many other diseases ranging from cancer, atherosclerosis, stroke, hypertension, inflammatory related disorders, and autoimmune diseases. METHODS: In this study, starting from the endocannabinoid mechanism of action in neuronal signaling, we highlight and discuss potential application and recent patents of cannabimimetic drugs in neurological disorders. RESULTS: The cannabinoid CB1 receptor was considered particularly interesting for therapeutic approaches in neurological diseases, because primarily expressed by neurons of the central nervous system. In many experimental models, these drugs act via this receptor, however, CB1 receptor independent mechanisms have been also described. Furthermore, endogenous ligands of cannabinoid receptors, the endocannabinoids, are potent modulators of the synaptic function in the brain. In neurological diseases, numerous studies reported modulation of the levels of endocannabinoids according to the phase of the disease and its progression. CONCLUSIONS: Finally, although the study of the mechanisms of action of these compounds is still unsolved, many reports and patents strongly suggest therapeutic potential of these compounds in neurological diseases. PMID- 27184694 TI - Crystallization behaviour of poly(ethylene oxide) under confinement in the electrospun nanofibers of polystyrene/poly(ethylene oxide) blends. AB - We have studied the confined crystallization behaviour of poly(ethylene oxide) (PEO) in the electrospun nanofibers of the phase-separated blends of polystyrene (PS) and PEO, where PS was present as the major component. The size and shape of PEO domains in the nanofibers were considerably different from those in the cast films, presumably because of the nano-dimensions of the nanofibers and the extensional forces experienced by the polymer solution during electrospinning. The phase-separated morphology in turn influenced the crystallization behaviour of PEO in the blend nanofibers. At a PEO weight fraction of >=0.3, crystallization occurred through a heterogeneous nucleation mechanism similar to that in cast blend films. However, as the PEO weight fraction in the blend nanofibers was reduced from 0.3 to 0.2, an abrupt transformation of the nucleation mechanism from the heterogeneous to predominantly homogenous type was observed. The change in the nucleation mechanism implied a drastic reduction of the spatial continuity of PEO domains in the nanofibers, which was not encountered in the cast film. The melting temperature and crystallinity of the PEO crystallites developed in the nanofibers were also significantly lower than those in the corresponding cast films. The phenomena observed were reconciled by the morphological observation, which revealed that the phase separation under the radial constraint of the nanofibers led to the formation of small-sized fibrillar PEO domains with limited spatial connectivity. The thermal treatment of the PS/PEO blend nanofibers above the glass transition temperature of PS induced an even stronger confinement effect on PEO crystallization. PMID- 27184695 TI - The future of the Primary Examination. AB - The objective of the Primary Examination is to ensure that trainees have the required level of knowledge and understanding of the four basic sciences of anatomy, pathology, physiology and pharmacology to underpin their further learning and development towards careers as emergency medicine physicians. The candidate is expected to show an understanding of the subject matter and demonstrate their ability to apply their knowledge to the practice of emergency medicine. As part of the curriculum review, ACEM undertook to implement changes to the Primary Examination in order to make it more clinically relevant. PMID- 27184696 TI - Predatory open access journals: Avoiding profiteers, wasted effort and fraud. PMID- 27184698 TI - Factors affecting maternal confidence and satisfaction in older Japanese primiparae during postpartum hospital stay. AB - The purpose of this study was to identify factors affecting maternal confidence and satisfaction in older Japanese primiparae during their postpartum hospital stay. Participants were Japanese primiparae (age >= 35) who delivered live singleton infants (n = 479). Questionnaires completed 1 day before discharge from hospital included the Postpartum Maternal Confidence Scale and the Postpartum Maternal Satisfaction Scale. Data were analysed using stepwise multiple regression for maternal confidence and stepwise logistic regression for maternal satisfaction, after controlling for delivery mode. Maternal confidence was negatively affected by feeling overwhelmed by postpartum routines, needing a longer time for feeding, and a pregnancy with complications. Satisfaction with the birth experience and a longer rooming-in period were related to greater maternal satisfaction. Lack of prior experiences with caring for babies and lack of communication with their partner about parenting role were also associated with lower confidence and satisfaction. These findings provide an important framework for nurses to teach and counsel older first-time mothers. PMID- 27184697 TI - Cross-sectional and longitudinal validation of a 13-item fatigue scale among Japanese postpartum mothers. AB - This study examined the psychometric properties of a 13-item fatigue scale for postpartum mothers. Japanese mothers (n = 2026) from a cohort study completed questionnaires (e.g. fatigue scale, Japanese version of the Edinburgh Postnatal Depression Scale, demographics) during their hospital stay after childbirth (baseline) and at 1, 2, 4 and 6 months postpartum. Initial factor analysis of baseline data revealed that the fatigue scale had three factors or subscales (physical, emotional and cognitive). Within-group analysis across each measurement time revealed the same three-factor structure with acceptable fit. Between-group analysis also showed longitudinal factorial invariance across time. The fatigue subscales had acceptable divergent and convergent validities with the depression scale. The subscale scores differed significantly based on participant background. The Japanese Fatigue Scale is a concise and informative tool for assessing aspects of fatigue in clinical settings and in the community. PMID- 27184699 TI - Building the capacity of nursing professionals in Cambodia: Insights from a bridging programme for faculty development. AB - To upgrade nursing instruction capacity in Cambodia, two bridging programmes were opened for the Bachelor of Science in Nursing simultaneously in-country and out of-country (Thailand). A descriptive qualitative study was conducted to assess effectiveness of both programmes jointly and to explore needs concerning the further development of nursing education. This study included interviews with 34 current or previous programme participants (nursing instructors or hospital preceptors) and 10 managers of collaborating institutions. New learning content, personal outcomes, challenges and obstacles and future needs were qualitatively coded to create categories and subcategories of data. Findings show that programme participants were most influenced by the new content areas (e.g. nursing theory and professionalism), active teaching-learning strategies and the full-time educational immersion afforded by the out-of-country programme. Programme participants who had returned to their workplaces also identified on going needs for employing new active teaching-learning approaches, curriculum revision, national standardization of nursing curricula and improvements in the teaching-learning infrastructure. Another outcome of this study is the development of a theoretical model for Nursing Capacity Building in Developing Countries that describes the need for intermediate and long-term planning as well as using both Bottom-Up and Edge-Pulling strategies. PMID- 27184700 TI - Sensing kuuki among visiting nurses. AB - This study aimed to explore how visiting nurses in Japan sense Kuuki (mood or atmosphere) in the homes of patients and families. Participants were 15 Japanese visiting nurses with experience sensing kuuki in homes of patients and families. Data were collected through two 90 min focus group interviews with experienced visiting nurses, and a qualitative content analysis was performed. The qualitative analysis showed that experienced visiting nurses sensed kuuki in eight ways. Kuuki differs based on type of illness, state of health and number of visits. Sensitivity to kuuki is thought to be linked to understanding of patient and family feelings, changes in the physical condition of patients and evaluation of nursing care delivery. Perception of kuuki also contributes to care planning especially on the very first home visit and when visiting terminally ill patients. PMID- 27184701 TI - Risk factors, cross-cultural stressors and postpartum depression among immigrant Chinese women in Japan. AB - The purpose of this mixed-method design study was to examine factors contributing to depression among immigrant Chinese women (primipara and multipara) (n = 22) delivering a child for the first time in Japan. Data were obtained just after hospital discharge by using the Edinburgh Postnatal Depression Scale (EPDS), the Social Support Scale, a new scale to measure cross-cultural stressors in the postpartum setting and a visual analogue scale for stress and a demographic survey. The average EPDS score was 9.0 (SD +/- 3.7) at 1-3 weeks postpartum; yet, more than half of the subjects (n = 12; 54.5%) were high risk for depression (EPDS >= 10). Low household income and primiparous status were associated with depression scores. New mothers with depression also reported more general stress and more cross-cultural stress in the postpartum setting, although social support appeared to mediate cross-cultural stressors. Semi-structured interviews were held with two immigrant women at high risk for depression; these new mothers described additional stress because they could not follow Zuoyuezi, an important postpartum Chinese tradition, in the Japanese hospital. These findings suggest that immigrant Chinese women are at higher risk for postpartum depression when they give birth for the first time in Japan. PMID- 27184702 TI - The effects of collaborative research-based programming on public health nurses and their practice. AB - The study aim was to evaluate a collaborative research-based program for public health nurses. The program was initiated by a college of nursing to address public health issues. Participants were 33 public health nurses who completed a questionnaire survey; data for 25 respondents were analyzed both quantitatively and qualitatively. To understand the experiences of nurses in depth, three group interviews were conducted with 14 nurses. Qualitative analysis revealed three major themes: (i) opportunities for learning from collaboration; (ii) developing competence of changes in practice; and (iii) openness to continuing practice improvement. Study participants reported practical changes and new openness to continued practice improvement. Thus, schools of nursing and public health nurses should welcome and invite opportunities to collaborate to address practice issues using research-based information. Because changing practice can only occur step by step, nursing educators and practitioners should cultivate an environment that expands professional development and addresses practice improvement. PMID- 27184704 TI - Meaning in Life: A conceptual model for disaster nursing practice. AB - This study aimed to develop a conceptual model for understanding meaning in life (MIL) using respondents' quotations in the primary qualitative studies. The primary studies were selected from the PsycINFO, PsycARTICLES and CINAHL databases using keywords 'meaning in life', 'meaning of life', 'purpose in life' and 'will to meaning'. Respondents' quotations in the primary studies were analysed interpretatively to identify MIL from the respondents' perspectives. The data were synthesized to integrate findings from 10 selected primary studies. The findings identified (i) six sources of MIL (e.g. having a significant others, having new experiences and performing spiritual activities); (ii) eight components of MIL (e.g. focusing on self, connecting to others, contributing to others and having a sense of direction and purpose); and (iii) the emotional outcomes of having MIL: happiness, satisfaction and joy. Through a discussion of the findings, a conceptual model of MIL emerged. PMID- 27184703 TI - Cultural characteristics of nursing practice in Japan. AB - The population of Japan has become multi-cultural, and there is more demand for culturally competent nursing care. The purpose of this study was to explore cultural characteristics of nursing practice in Japan focusing on behaviour. We interviewed 25 professionals with experience in or knowledge of nursing practice both in Japan and either the United States, the United Kingdom, Sweden, Thailand or South Korea. Qualitative content analysis has yielded three themes for cultural characteristics of nursing practice in Japan: practice expectations, communication and relationships with patients. Practice expectations for nurses in Japan involved various aspects; nurses conducted a wide range of basic nursing tasks, including bed baths and toileting. They often relied on non-verbal communication to deliver thoughtfulness and perceptiveness. They typically show deference to doctors and colleagues, emphasizing building and maintaining harmony with them. This emphasis on a multifaceted, non-verbal, and harmonious approach seemed characteristic of practice among Japanese nurses. PMID- 27184705 TI - Sigma-2 receptor ligand anchored telmisartan loaded nanostructured lipid particles augmented drug delivery, cytotoxicity, apoptosis and cellular uptake in prostate cancer cells. AB - Recently, the anticancer activity of telmisartan (TEL) has been discovered against prostate cancer. Nevertheless, despite favorable therapeutic profile, poor aqueous solubility and suboptimal oral bioavailability hamper the anticancer efficacy of TEL. Therefore, in this investigation, sigma-2 receptor ligand, 3-(4 cyclohexylpiperazine-1-yl) propyl amine (CPPA) anchored nanostructured lipid particles of telmisartan (CPPA-TEL-NLPs) were engineered using stearic acid for targeting prostate cancer, PC-3 cells. The mean particle size of TEL-NLPs was measured to be 25.4 +/- 3.2 nm, significantly (p < 0.05) lower than 32.6 +/- 5.3 nm of CPPA-TEL-NLPs. Correspondingly, the zeta-potential of TEL-NLPs was measured to be -15.4 +/- 2.3 mV significantly (p < 0.05) higher than -9.6 +/- 2.7 mV of CPPA-TEL-NLPs. The encapsulation efficiency of CPPA-TEL-NLPs was estimated to be 72.7 +/- 4.3%, significantly (p < 0.05) lower than 77.5 +/- 5.4%, displayed by TEL-NLPs. In addition, FT-IR and PXRD confirmed the molecular encapsulation of the drug in amorphous state. In vitro drug release study was conducted to determine the drug delivery potential of tailored nanoparticles. TEL-NLPs released 93.36% of drug significantly (p < 0.05) higher than 85.81%, released by CPPA-TEL-NLPs in 24 h. The IC50 of CPPA-TEL-NLPs was measured to be 20.3 uM significantly (p < 0.05) lower than 36.3 uM presented by TEL-NLPs in PC-3 cells. In contrast, CPPA-TEL-NLPs displayed the IC50 of 41.3 uM, significantly (p > 0.05) not different from 43.4 uM, exhibited by TEL-NLPs in PNT-2 cells. We elucidated that CPPA-TEL-NLPs entered the PC-3 cells via receptor mediated endocytosis pathway and thus exhibited superior cytotoxicity, apoptosis and greater extent of cellular uptake in PC-3 cells. In conclusion, CPPA-TEL-NLPs may be a promising nanomedicine and warrant further in vivo investigations for gaining clinical success. PMID- 27184707 TI - Compensation strategy to reduce geometry and mechanics mismatches in porous biomaterials built with Selective Laser Melting. AB - The accuracy of Additive Manufacturing processes in fabricating porous biomaterials is currently limited by their capacity to render pore morphology that precisely matches its design. In a porous biomaterial, a geometric mismatch can result in pore occlusion and strut thinning, drawbacks that can inherently compromise bone ingrowth and severely impact mechanical performance. This paper focuses on Selective Laser Melting of porous microarchitecture and proposes a compensation scheme that reduces the morphology mismatch between as-designed and as-manufactured geometry, in particular that of the pore. A spider web analog is introduced, built out of Ti-6Al-4V powder via SLM, and morphologically characterized. Results from error analysis of strut thickness are used to generate thickness compensation relations expressed as a function of the angle each strut formed with the build plane. The scheme is applied to fabricate a set of three-dimensional porous biomaterials, which are morphologically and mechanically characterized via micro Computed Tomography, mechanically tested and numerically analyzed. For strut thickness, the results show the largest mismatch (60% from the design) occurring for horizontal members, reduces to 3.1% upon application of the compensation. Similar improvement is observed also for the mechanical properties, a factor that further corroborates the merit of the design oriented scheme here introduced. PMID- 27184708 TI - Blood biomarkers of endocrine, immune, inflammatory, and metabolic systems in obstructive sleep apnea. AB - OBJECTIVE/BACKGROUND: Obstructive sleep apnea (OSA) is a common disorder, affecting over 100 million adults. Untreated OSA leads to serious health consequences and perturbations in endocrine, immune, inflammatory, and metabolic systems. Study objectives are to evaluate the association between OSA and biomarkers, and to test the hypothesis that a combination of markers may be useful in screening for OSA. PATIENTS/METHODS: A multicenter trial was conducted enrolling symptomatic male patients with suspected OSA. All subjects underwent in laboratory overnight polysomnography. A non-symptomatic control group was also obtained. Eleven biomarkers were tested: HbA1c, CRP, EPO, IL-6, uric acid, cortisol, hGH, prolactin, testosterone, DHEA (Beckman Coulter UniCel DxC 600i Synchron(r) Access(r) Clinical Systems), IGF-1. RESULTS: 73 male subjects were enrolled; 26 had moderate/severe OSA. ROC curve analysis showed HbA1c, CRP, EPO, IL-6, and Uric Acid (AUCs: 0.76, 0.73, 0.65, 0.65, 0.61) were superior to the Epworth Sleepiness Scale (AUC: 0.52). Concurrent elevation of HbA1c and CRP provide even greater predictive power. A combination of elevated HbA1c, CRP, and EPO provided 0.08 increase in AUC (0.84 [0.75 - 0.94]) over individual markers (p<0.05), with high sensitivity (85%), and specificity (79%) for moderate/severe OSA. CONCLUSIONS: OSA induces characteristic endocrine, immune, inflammatory, and metabolic disturbances that can be detected with blood biomarkers. These biomarkers are superior to standard screening questionnaires. Various clusters of these biomarkers have an even greater association with OSA and thus may represent physiologic signatures of the disorder that may have value in initial screening for OSA as well as for follow-up of therapy response. PMID- 27184706 TI - Nuclease Footprints in Sperm Project Past and Future Chromatin Regulatory Events. AB - Nuclear remodeling to a condensed state is a hallmark of spermatogenesis. This is achieved by replacement of histones with protamines. Regions retaining nucleosomes may be of functional significance. To determine their potential roles, sperm from wild type and transgenic mice harboring a single copy insert of the human protamine cluster were subjected to Micrococcal Nuclease-seq. CENTIPEDE, a hierarchical Bayesian model, was used to identify multiple spatial patterns, "footprints", of MNase-seq reads along the sperm genome. Regions predicted by CENTIPEDE analysis to be bound by a regulatory factor in sperm were correlated with genomic landmarks and higher order chromatin structure datasets to identify potential roles for these factors in regulating either prior or post spermatogenic, i.e., early embryonic events. This approach linked robust endogenous protamine transcription and transgene suppression to its chromatin environment within topologically associated domains. Of the candidate enhancer bound regulatory proteins, Ctcf, was associated with chromatin domain boundaries in testes and embryonic stem cells. The continuity of Ctcf binding through the murine germline may permit rapid reconstitution of chromatin organization following fertilization. This likely reflects its preparation for early zygotic genome activation and comparatively accelerated preimplantation embryonic development program observed in mouse as compared to human and bull. PMID- 27184709 TI - The impact of nonverbal ability on prevalence and clinical presentation of language disorder: evidence from a population study. AB - BACKGROUND: Diagnosis of 'specific' language impairment traditionally required nonverbal IQ to be within normal limits, often resulting in restricted access to clinical services for children with lower NVIQ. Changes to DSM-5 criteria for language disorder removed this NVIQ requirement. This study sought to delineate the impact of varying NVIQ criteria on prevalence, clinical presentation and functional impact of language disorder in the first UK population study of language impairment at school entry. METHODS: A population-based survey design with sample weighting procedures was used to estimate population prevalence. We surveyed state-maintained reception classrooms (n = 161 or 61% of eligible schools) in Surrey, England. From a total population of 12,398 children (ages 4-5 years), 7,267 (59%) were screened. A stratified subsample (n = 529) received comprehensive assessment of language, NVIQ, social, emotional and behavioural problems, and academic attainment. RESULTS: The total population prevalence estimate of language disorder was 9.92% (95% CI 7.38, 13.20). The prevalence of language disorder of unknown origin was estimated to be 7.58% (95% CI 5.33, 10.66), while the prevalence of language impairment associated with intellectual disability and/or existing medical diagnosis was 2.34% (95% CI 1.40, 3.91). Children with language disorder displayed elevated symptoms of social, emotional and behavioural problems relative to peers, F(1, 466) = 7.88, p = .05, and 88% did not make expected academic progress. There were no differences between those with average and low-average NVIQ scores in severity of language deficit, social, emotional and behavioural problems, or educational attainment. In contrast, children with language impairments associated with known medical diagnosis and/or intellectual disability displayed more severe deficits on multiple measures. CONCLUSIONS: At school entry, approximately two children in every class of 30 pupils will experience language disorder severe enough to hinder academic progress. Access to specialist clinical services should not depend on NVIQ. PMID- 27184710 TI - Next-generation biology: Sequencing and data analysis approaches for non-model organisms. AB - As sequencing technologies become more affordable, it is now realistic to propose studying the evolutionary history of virtually any organism on a genomic scale. However, when dealing with non-model organisms it is not always easy to choose the best approach given a specific biological question, a limited budget, and challenging sample material. Furthermore, although recent advances in technology offer unprecedented opportunities for research in non-model organisms, they also demand unprecedented awareness from the researcher regarding the assumptions and limitations of each method. In this review we present an overview of the current sequencing technologies and the methods used in typical high-throughput data analysis pipelines. Subsequently, we contextualize high-throughput DNA sequencing technologies within their applications in non-model organism biology. We include tips regarding managing unconventional sample material, comparative and population genetic approaches that do not require fully assembled genomes, and advice on how to deal with low depth sequencing data. PMID- 27184711 TI - Physical, Chemical, and Biological Structures based on ROS-Sensitive Moieties that are Able to Respond to Oxidative Microenvironments. AB - Reactive oxygen species (ROS) (H2 O2 , OCl(-) , (*) OH, O2 (-) ) are a family of reactive molecules that are generated intracellularly and are engaged in many biological processes. In physiological concentrations, ROS act as signaling molecules to a number of metabolic pathways; however, in excess they can be harmful to living organisms. Overproduction of ROS has been related to many pathophysiological conditions and a number of studies have been reported in elucidating their mechanism in these conditions. With the aim of harnessing this role, a number of imaging tools and therapeutic compounds have been developed. Here these imaging and therapeutic tools are reviewed and particularly those structures with ROS-sensitivity based on their biomedical applications and their functional groups. There is also a brief discussion about the method of preparation as well as the mechanism of action. PMID- 27184721 TI - Independent radiologic review of AURELIA, a phase 3 trial of bevacizumab plus chemotherapy for platinum-resistant recurrent ovarian cancer. AB - OBJECTIVE: The randomized, open-label, phase 3 Avastin(r) Use in Platinum Resistant Epithelial Ovarian Cancer (AURELIA) trial achieved its primary efficacy end point of significantly improved progression-free survival (PFS) in patients treated with bevacizumab in combination with chemotherapy (CT) compared with CT alone for platinum-resistant, recurrent ovarian cancer. Primary analyses were conducted via investigator assessment of PFS; to confirm primary results, an independent review committee (IRC) retrospectively assessed radiographic data. METHODS: Per an amendment to the original study protocol, the IRC reviewed radiographic data from 298 (82.5%) patients in a blinded manner using the Response Evaluation Criteria in Solid Tumors (modified version 1.0). IRC-assessed PFS and concordance between the two assessments were evaluated. RESULTS: IRC assessment demonstrated that PFS was significantly prolonged for patients treated with CT+bevacizumab compared with CT alone (median, 8.1 vs. 3.9months; hazard ratio, 0.484; 95% confidence interval, 0.370-0.632; P<0.0001). Results were similar to the primary PFS analysis from investigator assessment (median, 6.8 vs. 3.4months; hazard ratio, 0.384; 95% confidence interval, 0.300-0.491; P<0.0001). Concordance rates for progressive disease status (CT+bevacizumab, 68.2%; CT, 69.9%) and date (CT+bevacizumab, 67.2%; CT, 69.1%) were similar across treatment arms. Among 161 IRC-evaluable patients declared to have progressive disease by investigator and IRC assessment, 68.3% progressed on the same date as determined by both investigator and IRC. CONCLUSIONS: IRC assessment of PFS confirmed the investigator-assessed PFS improvement for patients treated with CT+bevacizumab compared with CT alone in the AURELIA study. PMID- 27184723 TI - Innovation: ZP2-coated beads decoy sperm. PMID- 27184724 TI - Prostate cancer: Nucleotyping predicts recurrence post-RP. PMID- 27184725 TI - Stones: Gut microbiome is unique in kidney stone disease. PMID- 27184722 TI - CP-25, a novel compound, protects against autoimmune arthritis by modulating immune mediators of inflammation and bone damage. AB - Paeoniflorin-6'-O-benzene sulfonate (code: CP-25), a novel ester derivative of paeoniflorin (Pae), was evaluated in rats with adjuvant-induced arthritis (AA) to study its potential anti-arthritic activity. AA rats were treated with CP-25 (25, 50, or 100 mg/kg) from days 17 to 29 after immunization. CP-25 effectively reduced clinical and histopathological scores compared with the AA groups. CP-25 treated rats exhibited decreases in pro-inflammatory cytokines (IL-1beta, IL-6, IL-17 and TNF-alpha) coupled with an increase in the anti-inflammatory cytokine TGF-beta1 in the serum. CP-25 treatment inhibited M1 macrophage activation and enhanced M2 macrophage activation by influencing cytokine production. Decreases in Th17-IL-17 and the Th17-associated transcription factor RAR-related orphan receptor gamma (ROR-gammat) dramatically demonstrated the immunomodulatory effects of CP-25 on abnormal immune dysfunction. In addition, CP-25 suppressed the production of receptor activator of nuclear factor kappa B ligand (RANKL) and matrix metalloproteinase (MMP) 9, which supported its anti-osteoclastic effects. The data presented here demonstrated that CP-25 significantly inhibited the progression of rat AA by reducing inflammation, immunity and bone damage. The protective effects of CP-25 in AA highlight its potential as an ideal new anti arthritic agent for human RA. PMID- 27184726 TI - H3O(+) tetrahedron induction in large negative linear compressibility. AB - Despite the rarity, large negative linear compressibility (NLC) was observed in metal-organic framework material Zn(HO3PC4H8PO3H)?2H2O (ZAG-4) in experiment. We find a unique NLC mechanism in ZAG-4 based on first-principle calculations. The key component to realize its large NLC is the deformation of H3O(+) tetrahedron. With pressure increase, the oxygen apex approaches and then is inserted into the tetrahedron base (hydrogen triangle). The tetrahedron base subsequently expands, which results in the b axis expansion. After that, the oxygen apex penetrates the tetrahedron base and the b axis contracts. The negative and positive linear compressibility is well reproduced by the hexagonal model and ZAG-4 is the first MOFs evolving from non re-entrant to re-entrant hexagon framework with pressure increase. This gives a new approach to explore and design NLC materials. PMID- 27184727 TI - Inventory management strategies that reduce the age of red blood cell components at the time of transfusion. AB - BACKGROUND: There has been interest concerning patient outcomes when older red blood cell (RBC) components are utilized. Inventory management is key to maintaining a stock of fresher RBCs for general transfusion needs. We have altered our practice for RBC management to reduce RBC age at the time of transfusion. STUDY DESIGN AND METHODS: Retrospective review of RBC age at time of transfusion at a tertiary care hospital with active trauma service was performed. The baseline nonirradiated RBC inventory was decreased from 12 to 15 days of stock to 7 to 10 days of stock, with request made to the blood supplier for fresher RBCs, specified at 75% of RBCs less than 14 days old. The age of RBCs at time of receipt and at time of transfusion was tracked on a monthly basis for the next 12 months. RESULTS: The mean age of RBCs at transfusion was decreased by 9 days on average for the year. Significant decreases in the mean age of RBCs at transfusion were seen in the second half of the year, with 4 of 6 months seeing a mean age of less than 20 days. There were no documented incidences of hospital blood shortages after the reduction in inventory; no surgery was canceled or delayed because of inventory. CONCLUSION: Inventory age depends on active management, combined with vendor cooperation to receive fresher components. Reducing the age of RBC components transfused is possible without experiencing blood component shortages. Longer periods of observation may allow for further adjustment of stocking levels on a seasonal basis. PMID- 27184728 TI - Cognition Predicts Quality of Life Among Patients With End-Stage Liver Disease. AB - BACKGROUND: Impaired cognitive functioning and poor quality of life (QoL) are both common among patients with end-stage liver disease; however, it is unclear how these are related. OBJECTIVE: This study examines how specific cognitive domains predict QoL among liver transplant candidates by replicating Stewart and colleagues' (2010) 3-factor model of cognitive functioning, and determining how variability in these cognitive domains predicts mental health and physical QoL. METHODS: The sample included 246 patients with end-stage liver disease who were candidates for liver transplant at a large, Midwestern health care center. Measures, including the Repeatable Battery for the Assessment of Neuropsychological Status, Trail Making Test, Shipley Institute of Living Scale, Short-Form Health Survey-36 Version 2, and Hospital Anxiety and Depression Scale, comprised latent variables representing global intellectual functioning, psychomotor speed, and learning and memory functioning. RESULTS: Confirmatory factor analysis results indicate that the 3-factor solution model comprised of global intellectual functioning, psychomotor speed, and learning and memory functioning fit the data well. Addition of physical and mental health QoL latent factors resulted in a structural model also with good fit. Results related physical QoL to global intellectual functioning, and mental health QoL to global intellectual functioning and psychomotor functioning. CONCLUSIONS: Findings elucidate a relationship between cognition and QoL and support the use of routine neuropsychological screening with end-stage liver disease patients, specifically examining the cognitive domains of global intellectual, psychomotor, and learning and memory functioning. Subsequently, screening results may inform implementation of targeted interventions to improve QoL. PMID- 27184729 TI - beta-CD Dimer-immobilized Ag Assembly Embedded Silica Nanoparticles for Sensitive Detection of Polycyclic Aromatic Hydrocarbons. AB - We designed a beta-CD dimer on silver nanoparticles embedded with silica nanoparticles (Ag@SiO2 NPs) structure to detect polycyclic aromatic hydrocarbons (PAHs). Silica NPs were utilized as a template for embedding silver NPs to create hot spot structures and enhance the surface-enhanced Raman scattering (SERS) signal, and a thioether-bridged dimeric beta-CD was immobilized on Ag NPs to capture PAHs. The assembled Ag NPs on silica NPs were confirmed by TEM and the presence of beta-CD dimer on Ag@SiO2 was confirmed by UV-vis and attenuated total reflection-Fourier transform infrared spectroscopy. The beta-CD dimer@Ag@SiO2 NPs were used as SERS substrate for detecting perylene, a PAH, directly and in a wide linearity range of 10(-7) M to 10(-2) M with a low detection limit of 10(-8) M. Also, the beta-CD dimer@Ag@SiO2 NPs exhibited 1000-fold greater sensitivity than Ag@SiO2 NPs in terms of their perylene detection limit. Furthermore, we demonstrated the possibility of detecting various PAH compounds using the beta-CD dimer@Ag@SiO2 NPs as a multiplex detection tool. Various PAH compounds with the NPs exhibited their distinct SERS bands by the ratio of each PAHs. This approach of utilizing the assembled structure and the ligands to recognize target has potential for use in sensitive analytical sensors. PMID- 27184731 TI - Comparison of three orientation and mobility aids for individuals with blindness: Verbal description, audio-tactile map and audio-haptic map. AB - Disorientation and inability of wayfinding are phenomena with a great frequency for individuals with visual impairments during the process of travelling novel environments. Orientation and mobility aids could suggest important tools for the preparation of a more secure and cognitively mapped travelling. The aim of the present study was to examine if spatial knowledge structured after an individual with blindness had studied the map of an urban area that was delivered through a verbal description, an audio-tactile map or an audio-haptic map, could be used for detecting in the area specific points of interest. The effectiveness of the three aids with reference to each other was also examined. The results of the present study highlight the effectiveness of the audio-tactile and the audio haptic maps as orientation and mobility aids, especially when these are compared to verbal descriptions. PMID- 27184730 TI - Therapeutic options of Angiotensin Receptor Neprilysin inhibitors (ARNis) in chronic heart failure with reduced ejection fraction: Beyond RAAS and sympathetic nervous system inhibition. AB - In heart failure, in addition to the renin-angiotensin-aldosterone system and sympathetic nervous system, the natriuretic peptide (NP) system plays a fundamental role among compensating mechanisms. The NPs undergo rapid enzymatic degradation that limits their vasorelaxant, natriuretic, and diuretic actions. Degradation of NPs is partially due to the action of neprilysin, which is a membrane-bound endopeptidase found in many tissues. This article summarizes recent findings on a new natriuretic peptide-enhancing drug and their implication for future pharmacological treatment of patients suffering from heart failure with reduced ejection fraction. PMID- 27184732 TI - Establishing a murine xenograft-model for long-term analysis of factors inducing chromosomal instability in myelodysplastic syndrome: Pitfalls and successes. AB - Myelodysplastic syndromes (MDS) are difficult to culture long-term showing the need of a model to study the fate of cells with MDS-abnormalities associated with chromosomal instability (CIN). This approach to establish a xenograft model transplanting human hematopoietic stem cells (HSC) with different independent lentivirally-mediated MDS-related modifications into immunodeficient mice is a long-lasting and tedious experiment with many parameters and every positive as well as non-functioning intermediate step will help the research community. As the establishment of appropriate xenograft models is increasing worldwide we aim to share our experiences to contribute toward minimizing loss of mice and following the "right" approach. Here, modified HSCs were intrafemorally transplanted into NSG and/or NSGS mice: (1) RPS14-haploinsufficiency, (2) TP53 deficiency, (3) TP53 hotspot mutations (R248W, R175H, R273H, R249S). Engraftment was achieved and cytogenetic analyses showed human cells with normal karyotypes. However, in all experiments with NSG mice, mainly control cells or GFP-negative cells were engrafted, not allowing observation of modified HSCs. In NSGS mice, engraftment rate was higher, but mice developed graft-versus-host disease. In summary, engraftment of HSCs is promising and could be used to analyze the induction of CIN. However, the analysis of modified HSCs is limited and further experiments are required to improve this model. PMID- 27184733 TI - Coupling of glutamate and glucose uptake in cultured Bergmann glial cells. AB - Glutamate, the main excitatory neurotransmitter in the vertebrate brain, exerts its actions through specific membrane receptors present in neurons and glial cells. Over-stimulation of glutamate receptors results in neuronal death, phenomena known as excitotoxicity. A family of sodium-dependent, glutamate uptake transporters mainly expressed in glial cells, removes the amino acid from the synaptic cleft preventing neuronal death. The sustained sodium influx associated to glutamate removal in glial cells, activates the sodium/potassium ATPase restoring the ionic balance, additionally, glutamate entrance activates glutamine synthetase, both events are energy demanding, therefore glia cells increase their ATP expenditure favouring glucose uptake, and triggering several signal transduction pathways linked to proper neuronal glutamate availability, via the glutamate/glutamine shuttle. To further characterize these complex transporters interactions, we used the well-established model system of cultured chick cerebellum Bergmann glia cells. A time and dose-dependent increase in the activity, plasma membrane localization and protein levels of glucose transporters was detected upon d-aspartate exposure. Interestingly, this increase is the result of a protein kinase C-dependent signaling cascade. Furthermore, a glutamate-dependent glucose and glutamate transporters co-immunoprecipitation was detected. These results favour the notion that glial cells are involved in glutamatergic neuronal physiology. PMID- 27184734 TI - PRICKLE1 Contributes to Cancer Cell Dissemination through Its Interaction with mTORC2. AB - Components of the evolutionarily conserved developmental planar cell polarity (PCP) pathway were recently described to play a prominent role in cancer cell dissemination. However, the molecular mechanisms by which PCP molecules drive the spread of cancer cells remain largely unknown. PRICKLE1 encodes a PCP protein bound to the promigratory serine/threonine kinase MINK1. We identify RICTOR, a member of the mTORC2 complex, as a PRICKLE1-binding partner and show that the integrity of the PRICKLE1-MINK1-RICTOR complex is required for activation of AKT, regulation of focal adhesions, and cancer cell migration. Disruption of the PRICKLE1-RICTOR interaction results in a strong impairment of breast cancer cell dissemination in xenograft assays. Finally, we show that upregulation of PRICKLE1 in basal breast cancers, a subtype characterized by high metastatic potential, is associated with poor metastasis-free survival. PMID- 27184735 TI - Effects of Reiki With Music Compared to Music Only Among People Living With HIV. AB - Persons living with HIV (PLWH) often seek complementary treatments to improve their overall health and well-being. Reiki, an ancient healing practice, has been found to be effective in reducing symptoms of stress, anxiety, pain, and depression. The purpose of this pilot study was to evaluate the effectiveness of Reiki as a complementary treatment for PLWH. Using a two-group mixed-methods experimental design, 37 participants were randomized to either a 6-week Reiki with Music Group or a Music Only Group. Self-reported and physiologic measures were obtained at baseline, 6 weeks, and 10 weeks. Significant improvements in relief of pain and stress in those receiving RMG were found. At the 6-week assessment, semi-structured interviews were conducted with all participants. Qualitative findings indicated that Reiki and music therapy helped reduce stress, anxiety, and depression. Evidence-based data regarding the effectiveness of Reiki will help nurses help patients better manage HIV-related symptoms. PMID- 27184736 TI - A Little Magic. PMID- 27184737 TI - Investigating the reinforcing value of binge anticipation. AB - Binge eating is a hallmark feature of several types of eating disorders, including bulimia nervosa, anorexia nervosa (binge/purge type), and binge-eating disorder, and is associated with numerous harmful consequences. For decades, researchers have sought to understand what maintains and reinforces this behavior in the face of such profound negative consequences. In this context, researchers have focused on the binge-eating behavior itself, and given little consideration to what may be a crucial part of the process: anticipating or planning binge eating episodes. In this article, we discuss binge anticipation, its potential reinforcing value, and methodologies which would allow researchers to investigate this potentially critical process in individuals who binge eat. (c) 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:539-541). PMID- 27184738 TI - Human tear proteomics and peptidomics in ophthalmology: Toward the translation of proteomic biomarkers into clinical practice. AB - : Tears are a complex biological mixture containing electrolytes, metabolites, lipids, mucins, some small organic molecules, and proteins. The tear film has various roles in the lubrication, protection from the external environment, and nutrition of the cornea; it is also involved in the modulation of the optical properties of the eye. Tear composition reflects the physiological condition of the underlying tissues. Therefore, the tear fluid is useful in the evaluation of health and disease states and it is a valuable source of biomarkers for objective analysis of ocular and systemic diseases. The relatively high protein concentration of this fluid and the ease of noninvasive sample collection make it suitable for diagnostic and prognostic purposes. Efforts in proteomics research have positively affected to the field of ophthalmology, and the knowledge on the tear proteome has expanded considerably in the last few years. Nevertheless, despite a large amount of available data and the many biomarkers proposed for several eye and systemic diseases, the extent of translation to well characterized and clinically useful tools has been largely insufficient. As for most of other biofluids, the road from discovery to clinical application is still long and full of pitfalls. In this review, we discuss the proteomic approaches used in the characterization of tear protein and peptide content, recapitulating the main studies and the progress done. We also present a brief summary of the path from discovery to clinical application of tear protein markers, with some representative examples of translation from the bench to the bedside. SIGNIFICANCE: In this review we cover the most relevant proteomic approaches used in the characterization of the tear proteome, and for the first time we also focus in advances performed in the nowadays emerging peptide content characterization. In this context, we recapitulate on the main studies and the progresses done in this field. We also present a concise overview of the course that may be happen from discovery to clinical application for tear protein markers. Finally we include some representative examples of translation from the bench to the bedside. PMID- 27184739 TI - Surface functionalized nanostructured ceramic sorbents for the effective collection and recovery of uranium from seawater. AB - The ability to collect uranium from seawater offers the potential for a nearly limitless fuel supply for nuclear energy. We evaluated the use of functionalized nanostructured sorbents for the collection and recovery of uranium from seawater. Extraction of trace minerals from seawater and brines is challenging due to the high ionic strength of seawater, low mineral concentrations, and fouling of surfaces over time. We demonstrate that rationally assembled sorbent materials that integrate high affinity surface chemistry and high surface area nanostructures into an application relevant micro/macro structure enables collection performance that far exceeds typical sorbent materials. High surface area nanostructured silica with surface chemistries composed of phosphonic acid, phosphonates, 3,4 hydroxypyridinone, and EDTA showed superior performance for uranium collection. A few phosphorous-based commercial resins, specifically Diphonix and Ln Resin, also performed well. We demonstrate an effective and environmentally benign method of stripping the uranium from the high affinity sorbents using inexpensive nontoxic carbonate solutions. The cyclic use of preferred sorbents and acidic reconditioning of materials was shown to improve performance. Composite thin films composed of the nanostructured sorbents and a porous polymer binder are shown to have excellent kinetics and good capacity while providing an effective processing configuration for trace mineral recovery from solutions. Initial work using the composite thin films shows significant improvements in processing capacity over the previously reported sorbent materials. PMID- 27184740 TI - Modified serpinA1 as risk marker for Parkinson's disease dementia: Analysis of baseline data. AB - Early detection of dementia in Parkinson disease is a prerequisite for preventive therapeutic approaches. Modified serpinA1 in cerebrospinal fluid (CSF) was suggested as an early biomarker for differentiation between Parkinson patients with (PDD) or without dementia (PD). Within this study we aimed to further explore the diagnostic value of serpinA1. We applied a newly developed nanoscale method for the detection of serpinA1 based on automated capillary isoelectric focusing (CIEF). A clinical sample of 102 subjects including neurologically healthy controls (CON), PD and PDD patients was investigated. Seven serpinA1 isoforms of different charge were detected in CSF from all three diagnostic groups. The mean CSF signals of the most acidic serpinA1 isoform differed significantly (p < 0.01) between PDD (n = 29) and PD (n = 37) or CON (n = 36). Patients above the cut-off of 6.4 have a more than six times higher risk for an association with dementia compared to patients below the cut off. We propose this serpinA1 CIEF-immunoassay as a novel tool in predicting cognitive impairment in PD patients and therefore for patient stratification in therapeutic trials. PMID- 27184742 TI - Use Dependent Attenuation of Rat HCN1-Mediated Ih in Intact HEK293 Cells. AB - BACKGROUND/AIMS: Cationic currents (Ih) through the fast activating and relatively cAMP insensitive subtype of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, HCN1, are limited by cytosolic factors in mammalian cells. This cytosolic HCN1 break is boosted by changes in membrane voltage that are not characterized on a biophysical level, yet. METHODS: We overexpressed rat (r)HCN1 in human embryonic kidney cells (HEK293) and recorded pharmacologically isolated Ih in cell-attached or whole-cell mode of the patch clamp technique. RESULTS: Recurring activation of rHCN1 reduced and slowed Ih in intact HEK293 cells (cell-attached mode). On the contrary, sustained disruption of the intracellular content (whole-cell mode) ceased activity dependence and partially enables voltage dependent hysteresis. The activity induced Ih attenuation in intact cells was independent of the main external cation, depended on the number of previous forced activations and was - at least in part - due to a shift in the voltage dependence of activation towards hyperpolarization as estimated by an adapted tail current analysis. Intracellular elevation of cAMP could not reverse the changes in Ih. CONCLUSION: Reduction of rHCN1 mediated Ih is use dependent and may involve the coupling of voltage sensor and pore. PMID- 27184743 TI - Cultural competence in mental health nursing: validity and internal consistency of the Portuguese version of the multicultural mental health awareness scale MMHAS. AB - BACKGROUND: Cultural competence is an essential component in rendering effective and culturally responsive services to culturally and ethnically diverse clients. Still, great difficulty exists in assessing the cultural competence of mental health nurses. There are no Portuguese validated measurement instruments to assess cultural competence in mental health nurses. This paper reports a study testing the reliability and validity of the Portuguese version of the Multicultural Mental Health Awareness Scale-MMHAS in a sample of Portuguese nurses. METHODS: Following a standard forward/backward translation into Portuguese, the adapted version of MMHAS, along with a sociodemographic questionnaire, were applied to a sample of 306 Portuguese nurses (299 males, 77 females; ages 21-68 years, M = 35.43, SD = 9.85 years). A psychometric research design was used with content and construct validity and reliability. Reliability was assessed using internal consistency and item-total correlations. Construct validity was determined using factor analysis. RESULTS: The factor analysis confirmed that the Portuguese version of MMHAS has a three-factor structure of multicultural competencies (Awareness, Knowledge, and Skills) explaining 59.51% of the total variance. Strong content validity and reliability correlations were demonstrated. The Portuguese version of MMHAS has a strong internal consistency, with a Cronbach's alpha of 0.958 for the total scale. CONCLUSIONS: The results supported the construct validity and reliability of the Portuguese version of MMHAS, proving that is a reliable and valid measure of multicultural counselling competencies in mental health nursing. The MMHAS Portuguese version can be used to evaluate the effectiveness of multicultural competency training programs in Portuguese-speaking mental health nurses. The scale can also be a useful in future studies of multicultural competencies in Portuguese-speaking nurses. PMID- 27184741 TI - Neonatal inflammatory pain and systemic inflammatory responses as possible environmental factors in the development of autism spectrum disorder of juvenile rats. AB - BACKGROUND: Autism spectrum disorder (ASD) affects many children and juveniles. The pathogenesis of ASD is not well understood. Environmental factors may play important roles in the development of ASD. We examined a possible relationship of inflammatory pain in neonates and the development of ASD in juveniles. METHODS: Acute inflammation pain was induced by 5 % formalin (5 MUl/day) subcutaneous injection into two hindpaws of postnatal day 3 to 5 (P3-P5) rat pups. Western blot, immunohistochemical, and behavioral examinations were performed at different time points after the insult. RESULTS: Formalin injection caused acute and chronic inflammatory responses including transient local edema, increased levels of inflammatory cytokines, TNF-alpha, and IL-1beta in the blood as well as in the brain, and increased microglia in the brain. One day after the pain insult, there was significant cell death in the cortex and hippocampus. Two weeks later, although the hindpaw local reaction subsided, impaired axonal growth and demyelization were seen in the brain of P21 juvenile rats. The number of bromodeoxyuridine (BrdU) and doublecortin (DCX) double-positive cells in the hippocampal dentate gyrus of P21 rats was significantly lower than that in controls, indicating reduced neurogenesis. In the P21 rat's brain of the formalin group, the expression of autism-related gene neurexin 1 (NRXN1), fragile X mental retardation 1 (FMR1), and oxytocin was significantly downregulated, consistent with the gene alteration in ASD. Juvenile rats in the formalin group showed hyperalgesia, repetitive behaviors, abnormal locomotion, sleep disorder, and distinct deficits in social memory and social activities. These alterations in neuroinflammatory reactions, gene expression, and behaviors were more evident in male than in female rats. Importantly, an anti-inflammation treatment using indomethacin (10 mg/kg, i.p.) at the time of formalin injections suppressed inflammatory responses and neuronal cell death and prevented alterations in ASD related genes and the development of abnormal behaviors. CONCLUSIONS: These novel observations indicate that severe inflammatory pain in neonates and persistent inflammatory reactions may predispose premature infants to development delays and psychiatric disorders including ASD. The prevention of pain stimuli and prompt treatments of inflammation during development appear vitally important in disrupting possible evolution of ASD syndromes. PMID- 27184744 TI - Increased chromosomal radiosensitivity in asymptomatic carriers of a heterozygous BRCA1 mutation. AB - BACKGROUND: Breast cancer risk increases drastically in individuals carrying a germline BRCA1 mutation. The exposure to ionizing radiation for diagnostic or therapeutic purposes of BRCA1 mutation carriers is counterintuitive, since BRCA1 is active in the DNA damage response pathway. The aim of this study was to investigate whether healthy BRCA1 mutations carriers demonstrate an increased radiosensitivity compared with healthy individuals. METHODS: We defined a novel radiosensitivity indicator (RIND) based on two endpoints measured by the G2 micronucleus assay, reflecting defects in DNA repair and G2 arrest capacity after exposure to doses of 2 or 4 Gy. We investigated if a correlation between the RIND score and nonsense-mediated decay (NMD) could be established. RESULTS: We found significantly increased radiosensitivity in the cohort of healthy BRCA1 mutation carriers compared with healthy controls. In addition, our analysis showed a significantly different distribution over the RIND scores (p = 0.034, Fisher's exact test) for healthy BRCA1 mutation carriers compared with non-carriers: 72 % of mutation carriers showed a radiosensitive phenotype (RIND score 1-4), whereas 72 % of the healthy volunteers showed no radiosensitivity (RIND score 0). Furthermore, 28 % of BRCA1 mutation carriers had a RIND score of 3 or 4 (not observed in control subjects). The radiosensitive phenotype was similar for relatives within several families, but not for unrelated individuals carrying the same mutation. The median RIND score was higher in patients with a mutation leading to a premature termination codon (PTC) located in the central part of the gene than in patients with a germline mutation in the 5' end of the gene. CONCLUSIONS: We show that BRCA1 mutations are associated with a radiosensitive phenotype related to a compromised DNA repair and G2 arrest capacity after exposure to either 2 or 4 Gy. Our study confirms that haploinsufficiency is the mechanism involved in radiosensitivity in patients with a PTC allele, but it suggests that further research is needed to evaluate alternative mechanisms for mutations not subjected to NMD. PMID- 27184747 TI - Socioeconomic gradients in early childhood health: evidence from Bangladesh and Nepal. AB - BACKGROUND: A large literature has developed researching the origins of socioeconomic gradients in child health in developed countries. Particularly, this research examines the age at which these gradient effects emerge and how they change across different stages of childhood. However, similar research on developing countries is limited. METHODS: This paper examines the socioeconomic gradients in early childhood health in two developing countries, Bangladesh and Nepal using the 2011 Demographic and Health Surveys. The paper separately studies two measures of household socioeconomic status: household wealth and maternal educational attainment. Two anthropometric measures of early childhood health, height-for-age and weight-for-age Z scores for 0-59 months of children, are used for our empirical exercise. The paper uses both non-parametric and multivariate ordinary least squares approaches to examine at what age socioeconomic disparities in health emerge, and investigates if these disparities increase with age in early childhood. RESULTS: The paper provides significant evidence of age specific socioeconomic gradients in early childhood health in both countries. Health disparities in household wealth exist in both countries. This disparity emerges in the first 11 months of life, and is particularly severe for children from the poorest quintile. On the other hand, while the emergence of maternal education gradients during the first 11 months is sensitive to the choice of childhood health measure, the study finds the children of mothers with higher education to enjoy significantly higher health outcomes in comparison to those with lower education. However, controlling for father's education weakens the effects of maternal education on child health in both countries. Further, the paper does not find statistically significant evidence where socioeconomic gradients in health increase with age in early childhood. CONCLUSIONS: Our study concludes that socioeconomic disparities in health outcomes exist even in very early childhood in Bangladesh and Nepal. This has important implications for targeted policy interventions in the form of food security and nutrition supplement programs, free provision of health care, and maternal education in both countries. PMID- 27184746 TI - Evidence for the functional involvement of members of the TRP channel family in the uptake of Na(+) and NH4 (+) by the ruminal epithelium. AB - Large quantities of protein are degraded in the fermentative parts of the gut to ammonia, which is absorbed, detoxified to urea, and excreted, leading to formation of nitrogenous compounds such as N2O that are associated with global warming. In ruminants, channel-mediated uptake of NH4 (+) from the rumen predominates. The molecular identity of these channels remains to be clarified. Ruminal cells and epithelia from cows and sheep were investigated using patch clamp, Ussing chamber, microelectrode techniques, and qPCR. In patch clamp experiments, bovine ruminal epithelial cells expressed a conductance for NH4 (+) that could be blocked in a voltage-dependent manner by divalent cations. In the native epithelium, NH4 (+) depolarized the apical potential, acidified the cytosol and induced a rise in short-circuit current (I sc) that persisted after the removal of Na(+), was blocked by verapamil, enhanced by the removal of divalent cations, and was sensitive to certain transient receptor potential (TRP) channel modulators. Menthol or thymol stimulated the I sc in Na(+) or NH4 (+) containing solutions in a dose-dependent manner and modulated transepithelial Ca(2+) fluxes. On the level of messenger RNA (mRNA), ovine and bovine ruminal epithelium expressed TRPA1, TRPV3, TRPV4, TRPM6, and TRPM7, with any expression of TRPV6 marginal. No bands were detected for TRPV1, TRPV5, or TRPM8. Functional and molecular biological data suggest that the transport of NH4 (+), Na(+), and Ca(2+) across the rumen involves TRP channels, with TRPV3 and TRPA1 emerging as prime candidate genes. TRP channels may also contribute to the transport of NH4 (+) across other epithelia. PMID- 27184745 TI - The eNOS signalosome and its link to endothelial dysfunction. AB - Endothelial nitric oxide synthase (eNOS) plays an essential role in the regulation of endothelial function and acts as a master regulator of vascular tone and homeostasis through the generation of the gasotransmitter nitric oxide (NO). The complex network of events mediating efficient NO synthesis is regulated by post-translational modifications and protein-protein interactions. Dysregulation of these mechanisms induces endothelial dysfunction, a term often used to refer to reduced NO bioavailability and consequent alterations in endothelial function, that are a hallmark of many cardiovascular diseases. Endothelial dysfunction is linked to eNOS uncoupling, which consists of a switch from the generation of NO to the generation of superoxide anions and hydrogen peroxide. This review provides an overview of the eNOS signalosome, integrating past and recently described protein-protein interactions that have been shown to play a role in the modulation of eNOS activity with implications for cardiovascular pathophysiology. The mechanisms underlying eNOS uncoupling and clinically relevant strategies that were adopted to influence them are also discussed. PMID- 27184751 TI - Putting the Conversation about Gun Ownership and Safety in Context. PMID- 27184749 TI - Assessing soil erosion risk using RUSLE through a GIS open source desktop and web application. AB - Soil erosion is a serious environmental problem. An estimation of the expected soil loss by water-caused erosion can be calculated considering the Revised Universal Soil Loss Equation (RUSLE). Geographical Information Systems (GIS) provide different tools to create categorical maps of soil erosion risk which help to study the risk assessment of soil loss. The objective of this study was to develop a GIS open source application (in QGIS), using the RUSLE methodology for estimating erosion rate at the watershed scale (desktop application) and provide the same application via web access (web application). The applications developed allow one to generate all the maps necessary to evaluate the soil erosion risk. Several libraries and algorithms from SEXTANTE were used to develop these applications. These applications were tested in Montalegre municipality (Portugal). The maps involved in RUSLE method-soil erosivity factor, soil erodibility factor, topographic factor, cover management factor, and support practices-were created. The estimated mean value of the soil loss obtained was 220 ton km(-2) year(-1) ranged from 0.27 to 1283 ton km(-2) year(-1). The results indicated that most of the study area (80 %) is characterized by very low soil erosion level (<321 ton km(-2) year(-1)) and in 4 % of the studied area the soil erosion was higher than 962 ton km(-2) year(-1). It was also concluded that areas with high slope values and bare soil are related with high level of erosion and the higher the P and C values, the higher the soil erosion percentage. The RUSLE web and the desktop application are freely available. PMID- 27184748 TI - Initiation and completion rates for latent tuberculosis infection treatment: a systematic review. AB - BACKGROUND: Control of latent tuberculosis infection (LTBI) is an important step towards tuberculosis elimination. Preventive treatment will prevent the development of disease in most cases diagnosed with LTBI. However, low initiation and completion rates affect the effectiveness of preventive treatment. The objective was to systematically review data on initiation rates and completion rates for LTBI treatment regimens in the general population and specific populations with LTBI. METHODS: A systematic review of the literature (PubMed, Embase) published up to February 2014 was performed. RESULTS: Forty-five studies on initiation rates and 83 studies on completion rates of LTBI treatment were found. These studies provided initiation rates (IR) and completion rates (CR) in people with LTBI among the general population (IR 26-99 %, CR 39-96 %), case contacts (IR 40-95 %, CR 48-82 %), healthcare workers (IR 47-98 %, CR 17-79 %), the homeless (IR 34-90 %, CR 23-71 %), people who inject drugs (IR 52-91 %, CR 38 89 %), HIV-infected individuals (IR 67-92 %, CR 55-95 %), inmates (IR 7-90 %, CR 4-100 %), immigrants (IR 23-97 %, CR 7-86 %), and patients with comorbidities (IR 82-93 %, CR 75-92 %). Generally, completion rates were higher for short than for long LTBI treatment regimens. CONCLUSION: Initiation and completion rates for LTBI treatment regimens were frequently suboptimal and varied greatly within and across different populations. PMID- 27184750 TI - Between Scylla and Charybdis: reconciling competing data management demands in the life sciences. AB - BACKGROUND: The widespread sharing of biologicaConcluding Comments: Teaching Responsible Datal and biomedical data is recognised as a key element in facilitating translation of scientific discoveries into novel clinical applications and services. At the same time, twenty-first century states are increasingly concerned that this data could also be used for purposes of bioterrorism. There is thus a tension between the desire to promote the sharing of data, as encapsulated by the Open Data movement, and the desire to prevent this data from 'falling into the wrong hands' as represented by 'dual use' policies. Both frameworks posit a moral duty for life sciences researchers with respect to how they should make their data available. However, Open data and dual use concerns are rarely discussed in concert and their implementation can present scientists with potentially conflicting ethical requirements. DISCUSSION: Both dual use and Open data policies frame scientific data and data dissemination in particular, though different, ways. As such they contain implicit models for how data is translated. Both approaches are limited by a focus on abstract conceptions of data and data sharing. This works to impede consensus-building between the two ethical frameworks. As an alternative, this paper proposes that an ethics of responsible management of scientific data should be based on a more nuanced understanding of the everyday data practices of life scientists. Responsibility for these 'micromovements' of data must consider the needs and duties of scientists as individuals and as collectively-organised groups. Researchers in the life sciences are faced with conflicting ethical responsibilities to share data as widely as possible, but prevent it being used for bioterrorist purposes. In order to reconcile the responsibilities posed by the Open Data and dual use frameworks, approaches should focus more on the everyday practices of laboratory scientists and less on abstract conceptions of data. PMID- 27184753 TI - Things Fall Apart: Preventing High Readmission Rates Among Homeless Adults. PMID- 27184752 TI - HPV Update: Vaccination, Screening, and Associated Disease. AB - Human papillomavirus (HPV) infection is the causative agent in cervical cancer, and is associated with numerous other genital cancers, including vulvar, vaginal, and anal cancer. Primary prevention with HPV vaccination is safe and efficacious, and a recently approved HPV vaccine will provide even more extensive protection against several oncogenic HPV strains. Screening strategies for HPV are rapidly evolving, reflecting the essential role that HPV infection plays in cervical cancer. This article highlights new evidence regarding the efficacy of the recently approved 9-valent HPV (9vHPV) vaccine and the use of primary high-risk HPV testing in cervical cancer screening. We consider the utility of urinary HPV testing in routine clinical practice and review current guidelines regarding anal HPV screening. PMID- 27184754 TI - Plasma C16-Cer levels are increased in patients with preterm labor. AB - INTRODUCTION: The pathogenesis of preterm labor is fragmentarily explained. The most widely accepted theory points out to infection and inflammation as possible causes, which can be mediated by potentially different factors, including sphingolipid mediators. Sphingolipids are a class of lipids that have been shown as important mediators in various cell processes such as: proliferation, growth, apoptosis, stress response, necrosis and inflammation. The aim of the study was to assess plasma concentrations of selected sphingolipids in patients with preterm labor. MATERIAL AND METHODS: We used ultra-high performance liquid chromatography with triple mass spectrometry (UHPLC-ESI-MS/MS) to assess plasma concentrations of the 11 sphingolipids in patients presenting with symptoms of preterm labor (n=61) and threatened preterm labor (n=40). RESULTS: We observed a statistically significant increase (p-value<0.004) in plasma concentrations of C16-Cer in patients with preterm labor as compared to the control group. We also found C16-Cer to be the best predictor of preterm labor in the group of patients with symptoms occurring after 32 weeks of gestation. CONCLUSIONS: Our findings show a possible involvement of selected sphingolipids, especially C16-Cer, in the pathogenesis of preterm labor. Their role as predictors of preterm delivery needs to be validated in the future on larger group of patients. PMID- 27184755 TI - EETs/sEH in diabetes and obesity-induced cardiovascular diseases. AB - Despite the optimization of blood glucose control and the therapeutic management of risk factors, obesity- and diabetes-induced cardiovascular diseases are still major health problems in the United States. Arachidonic acid (AA), an endogenous 20-carbon polyunsaturated fatty acid, is metabolized by cytochrome P450 (CYP) epoxygenases into epoxyeicosatrienoic acids (EETs), which are important lipid mediators with many beneficial effects in type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), and obesity- and diabetes-induced cardiovascular diseases. EETs can be further metabolized to less active dihydroxyeicosatrienoic acids (DHETs) by soluble epoxide hydrolase (sEH). It has been demonstrated that the use of sEH blockers, which prevent EET degradation, is a promising pharmacological approach to promoting insulin secretion, preventing endothelial dysfunction, decreasing blood pressure, and protecting against target organ damage in obesity and metabolic diseases. This review will focus on biochemistry of CYP monooxygenase system as well as the pharmacology and physiological significance of EETs and sEH. We will also discuss the role of EETs/sEH in T1DM, T2DM, and obesity- and diabetes-induced cardiovascular diseases. PMID- 27184756 TI - [Development and implementation of the Chronicity Strategy for the Basque Country (Spain): lessons learned]. AB - Public healthcare in the Basque Country (Spain) faces high rates of ageing and chronicity, which stress the sustainability of the system. In response to this situation, the Basque Chronicity Strategy was launched in 2010. This large-scale and far-reaching transformation initiative focused on changing the healthcare provision model towards integrated care of chronicity. Developed in the context of economic and financial crisis, strong political opposition and resistance or passivity of many relevant stakeholders, the design and implementation of the Strategy introduced some noteworthy elements, such as: a narrative of change different to the austerity discourse, which was the dominant narrative at that time; a strategic approach supported by an evidence base and solid theoretical references; and an implementation strategy that favoured local innovation and the "bottom up" approach. In spite of this, it was not possible to overcome the political barriers or bureaucratic immobility, which limited the implementation and scope of the changes, especially those related to the scalability of successful local innovations. However, some changes in the healthcare integration culture at clinical and managerial level have been introduced as a result of the Strategy, as well as organisational progression towards a chronicity-targeted healthcare model. PMID- 27184757 TI - [Evictions and health, a response from the public health in Spain is needed]. PMID- 27184759 TI - Effect of vitamin D supplementation, directly or via breast milk for term infants, on serum 25 hydroxyvitamin D and related biochemistry, and propensity to infection: a randomised placebo-controlled trial. AB - We assessed the effect of vitamin D supplementation on related biochemistry, infection and dentition of the infant. In a double-blind, placebo-controlled trial conducted in Lucknow, India (latitude 26 degrees N), 230 mother -newborn pairs were randomised to receive, for 9 months, 3000ug/month oral vitamin D3 by the mother (group A) or 10ug/d by the infant (group B) or double placebo (group C). All babies received 15 min of sun exposure (unclothed) during massage. Infants' median 25-hydroxyvitamin D (25(OH)D) was lower in group C (median 45.3; interquartile range (IQR) 22-59.5 nmol/l) than in groups A (median 60.8; IQR 41.3 80.5 nmol/l (P7.5ukat/l) was significantly more frequent in group C babies (16 %) than in group A (4 %) or group B (0 %) babies. The number of days with respiratory or diarrhoeal infection by 9 months of age was higher in group C (median 46.5; IQR 14.8-73.3 d) than in group A (median 18.5; IQR 8.8-31.0 d (P<0.01)) or group B (median 13.0; IQR 7.0-28.5 (P<0.05)). We conclude that monthly maternal or daily infant supplementation with vitamin D along with sun exposure is superior to sun exposure alone in maintaining normal infant 25(OH)D at 3.5 months, and provide protection from elevated alkaline phosphatase and infectious morbidity. PMID- 27184758 TI - Plutella xylostella granulovirus late gene promoter activity in the context of the Autographa californica multiple nucleopolyhedrovirus genome. AB - Within Baculoviridae, little is known about the molecular mechanisms of replication in betabaculoviruses, despite extensive studies in alphabaculoviruses. In this study, the promoters of nine late genes of the betabaculovirus Plutella xylostella granulovirus (PlxyGV) were cloned into a transient expression vector and the alphabaculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV) genome, and compared with homologous late gene promoters of AcMNPV in Sf9 cells. In transient expression assays, all PlxyGV late promoters were activated in cells transfected with the individual reporter plasmids together with an AcMNPV bacmid. In infected cells, reporter gene expression levels with the promoters of PlxyGV e18 and AcMNPV vp39 and gp41 were significantly higher than those of the corresponding AcMNPV or PlxyGV promoters, which had fewer late promoter motifs. Observed expression levels were lower for the PlxyGV p6.9, pk1, gran, p10a, and p10b promoters than for the corresponding AcMNPV promoters, despite equal numbers of late promoter motifs, indicating that species-specific elements contained in some late promoters were favored by the native viral RNA polymerases for optimal transcription. The 8-nt sequence TAAATAAG encompassing the ATAAG motif was conserved in the AcMNPV polh, p10, and pk1 promoters. The 5-nt sequence CAATT located 4 or 5 nt upstream of the T/ATAAG motif was conserved in the promoters of PlxyGV gran, p10c, and pk1. The results of this study demonstrated that PlxyGV late gene promoters could be effectively activated by the RNA polymerase from AcMNPV, implying that late gene expression systems are regulated by similar mechanisms in alphabaculoviruses and betabaculoviruses. PMID- 27184762 TI - Palladium-Catalyzed Carboxylation of Activated Vinylcyclopropanes with CO2. AB - By using a palladium catalyst with ZnEt2, activated vinylcyclopropanes were successfully converted into the corresponding beta,gamma-unsaturated carboxylic acids in high yields under a CO2 atmosphere (1 atm). The intermediate in this reaction is thought to be a nucleophilic eta(1)-allylethylpalladium species, which would be produced from pi-allylpalladium and ZnEt2 (umpolung reactivity). PMID- 27184761 TI - Binding of ATGs to Endothelial Cells In Vivo. AB - BACKGROUND Polyclonal anti-thymocyte globulins (ATGs) are immunosuppressive drugs widely used in induction of immunosuppression and treatment of acute rejection after solid organ transplantation. We have previously demonstrated that ATGs bind to endothelial cells in vitro, and are able to modulate ECs. The aim of this study was to investigate the binding of ATGs to endothelial cells under in vivo conditions. MATERIAL AND METHODS Muscle biopsies from extremities of cynomolgus monkeys were obtained after ischemia/reperfusion at 4 degrees C. ATGs (Thymoglobulin, Sanofi-Aventis, France; 1 mg/kg) were added to the blood 30 min prior to the reperfusion. Biopsies (n=10) of patients undergoing heart transplantation and preoperatively treated with ATGs (Thymoglobulin, Sanofi Aventis, France; 1.5 mg/kg) as induction therapy were also analyzed 6 hours and 7 days after induction. Binding of ATGs to ECs was analyzed with an anti-rabbit IgG antibody by means of immunohistochemistry. RESULTS Binding of ATGs to endothelial cells could be demonstrated in vivo in our animal experiments 4 hours after reperfusion, as well as in the clinical biopsies 6 hours after induction of immunosuppression in heart transplant patients, showing a preferred localization in post-capillary veins. No expression of ATGs on the endothelial surface could be observed after 7 days, suggesting that ATGs may be washed out from the endothelial surface in a time-dependent manner. CONCLUSIONS Our results show that ATGs are able to bind to endothelial cells in an experimental model and in clinical practice, supporting preconditioning strategies with ATGs in solid organ transplantation. PMID- 27184760 TI - Plasmodium falciparum gametocyte transit through the cutaneous microvasculature: A new target for malaria transmission blocking vaccines? AB - Malaria remains one of the most significant infectious diseases worldwide. Concordant with scaled intervention efforts and the emphasis of elimination and eradication on the agenda of many malaria control programs, the development of a malaria vaccine that reduces transmission of the parasite from human host to mosquito vector has been incorporated as an important new strategic goal. Transmission of malaria from man to mosquito relies on gametocytes, highly specialized sexual-stage parasites, that once mature, circulate in the peripheral vasculature of the human host. The complex interplay between mature gametocytes, their uptake in the mosquito bloodmeal and forward maturation/fertilization events provide unique opportunities for intervention. Although recent advances have yielded greater understanding into the mechanisms that mediate sequestration of immature gametocytes in the human host, the spatial dynamics of circulating mature gametocytes in the cutaneous microvaculature remains far less defined, which is the focus of this review. PMID- 27184764 TI - Fascin-1 as a novel diagnostic marker of triple-negative breast cancer. AB - In some cases of breast cancer, diagnosis of triple-negative breast cancer (TNBC) requires further fluorescence in situ hybridization (FISH) for determining human epidermal growth factor receptor 2 (HER2) status. However, few cases undergo FISH in China, leading to difficulty regarding subsequent treatment decisions. Here, we used immunohistochemical analysis to explore expression of fascin-1, an actin bundling protein, as a diagnostic marker of TNBC. A total of 457 cases of breast cancer were divided into four molecular subtypes, including 82 cases (17.9%) of TNBC, 81 (17.7%) of HER2-enriched, 185 (40.5%) of luminal A, and 109 (23.9%) of luminal B. Positive fascin-1 expression was seen in 144 cases (31.5%), including 77 (16.8%) strong positive cases. Rates of positive and strong positive expression of fascin-1 were significantly higher in cases of TNBC than in the other molecular subtypes. In all cases of breast cancer, the sensitivities and specificities of positive and strong positive fascin-1 expression for predicting TNBC were 87.8% and 80.8%, and 78.0% and 96.5%, respectively. In cases of hormone receptor-negative breast cancer, the sensitivities and specificities of positive and strong positive fascin-1 expression for predicting TNBC were 87.8% and 61.7%, and 78.0% and 92.6%, respectively. In 24 cases with estrogen receptor (ER)-, PR-, and HER2 2 + equivocal status who underwent FISH, the sensitivity and specificity of strong positive fascin-1 expression for predicting TNBC were 71.4% and 90.0%. These results suggest that strong positive fascin-1 expression can be used as a diagnostic marker of TNBC. PMID- 27184763 TI - HyCCAPP as a tool to characterize promoter DNA-protein interactions in Saccharomyces cerevisiae. AB - Currently available methods for interrogating DNA-protein interactions at individual genomic loci have significant limitations, and make it difficult to work with unmodified cells or examine single-copy regions without specific antibodies. In this study, we describe a physiological application of the Hybridization Capture of Chromatin-Associated Proteins for Proteomics (HyCCAPP) methodology we have developed. Both novel and known locus-specific DNA-protein interactions were identified at the ENO2 and GAL1 promoter regions of Saccharomyces cerevisiae, and revealed subgroups of proteins present in significantly different levels at the loci in cells grown on glucose versus galactose as the carbon source. Results were validated using chromatin immunoprecipitation. Overall, our analysis demonstrates that HyCCAPP is an effective and flexible technology that does not require specific antibodies nor prior knowledge of locally occurring DNA-protein interactions and can now be used to identify changes in protein interactions at target regions in the genome in response to physiological challenges. PMID- 27184765 TI - Synthesis and antitubercular evaluation of novel dibenzo[b,d]thiophene tethered imidazo[1,2-a]pyridine-3-carboxamides. AB - A series of novel dibenzo[b,d]thiophene tethered imidazo[1,2-a]pyridine carboxamides 7a-s were designed and synthesized. The required building block, 2 dibenzo[b,d]thiophenyl imidazo[1,2-a]pyridine carboxylic acid (5) was synthesized from commercial dibenzo[b,d]thiophene in good yields following five-step reaction sequence. The desired carboxamides 7a-s was prepared through coupling of acid 5 with various benzyl amines. All the new analogues 7a-s was characterized by their NMR and mass spectral analysis. Among nineteen new compounds 7a-s screened for in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv, three compounds 7k (MIC: 0.78MUg/mL); 7e and 7n (MIC: 1.56MUg/mL) were identified as potent analogues with low cytotoxicity. The results reported here will help global efforts for identification of potential lead antimycobacterial agents. PMID- 27184766 TI - Synthesis, antitumor evaluation and molecular docking studies of [1,2,4]triazolo[4,3-b][1,2,4,5]tetrazine derivatives. AB - A series of [1,2,4]triazolo[4,3-b][1,2,4,5]tetrazine derivatives have been synthesized and evaluated for their antitumor activities. These compounds exhibited potent antiproliferative activities against MCF-7, Bewo and HL-60 cells and c-Met kinase inhibitory activities. Three compounds were highly effective against MCF-7, Bewo and HL-60 cells with IC50 values in 1.09-2.24MUM. Molecular docking was further performed to study the inhibitor-c-Met kinase interactions, and the results show that compound 4j was potently bound to the c-Met kinase with three hydrogen bonds. The further research on acute toxicity and in vivo antitumor activity of compound 4j to ICR (Institute of Cancer Research) mice were carried out, and found 4j with a certain toxicity but good efficacy in vivo. Based on the preliminary results, it is deduced that compound 4j with potent c Met kinase inhibitory activity may be a potential anticancer agent. PMID- 27184767 TI - GroEL/ES inhibitors as potential antibiotics. AB - We recently reported results from a high-throughput screening effort that identified 235 inhibitors of the Escherichia coli GroEL/ES chaperonin system [Bioorg. Med. Chem. Lett.2014, 24, 786]. As the GroEL/ES chaperonin system is essential for growth under all conditions, we reasoned that targeting GroEL/ES with small molecule inhibitors could be a viable antibacterial strategy. Extending from our initial screen, we report here the antibacterial activities of 22 GroEL/ES inhibitors against a panel of Gram-positive and Gram-negative bacteria, including E. coli, Bacillus subtilis, Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter cloacae. GroEL/ES inhibitors were more effective at blocking the proliferation of Gram-positive bacteria, in particular S. aureus, where lead compounds exhibited antibiotic effects from the low-MUM to mid-nM range. While several compounds inhibited the human HSP60/10 refolding cycle, some were able to selectively target the bacterial GroEL/ES system. Despite inhibiting HSP60/10, many compounds exhibited low to no cytotoxicity against human liver and kidney cell lines. Two lead candidates emerged from the panel, compounds 8 and 18, that exhibit >50-fold selectivity for inhibiting S. aureus growth compared to liver or kidney cell cytotoxicity. Compounds 8 and 18 inhibited drug-sensitive and methicillin-resistant S. aureus strains with potencies comparable to vancomycin, daptomycin, and streptomycin, and are promising candidates to explore for validating the GroEL/ES chaperonin system as a viable antibiotic target. PMID- 27184768 TI - Tailoring nutrient sequence and content to improve glucose tolerance: Why and how to do it. PMID- 27184769 TI - Clinical outcomes following bifurcation double-stenting with bioresorbable scaffolds. AB - OBJECTIVES: To investigate outcomes following bifurcation double-stenting utilizing a bioresorbable scaffold (BRS) in the main branch (MB) and either a BRS or metallic drug-eluting stent (DES) in the side branch (SB). BACKGROUNDS: Data on outcomes of bifurcation lesions treated with BRSs, especially with double stenting, are currently lacking. METHODS: Data were examined from 42 de novo bifurcation lesions (41 patients) treated with double-stenting utilizing Absorb BRS in MB and BRS/DES in SB. Clinical outcomes including cardiac death, follow-up myocardial infarction, target lesion revascularization (TLR), and definite scaffold/stent thrombosis (ST) were investigated. RESULTS: The majority of target lesions were left anterior descending artery (LAD) bifurcations, and intravascular imaging was used in the majority of cases (92.9%). In SBs, BRSs were utilized in 19 lesions (19 patients) and DESs in 23 lesions (22 patients). Angiographic success was achieved in all lesions. The median follow-up was 594 days (interquartile range 214 - 838 days). The overall TLR-rates were 9.7% at 1 year and 14.0% at 2 years (MB-TLR: 6.9% at 1 year and 11.1% at 2 years; SB TLR: 9.7% at 1 year and 14.0% at 2 years). No definite ST was observed during follow up. TLR rates in both the MB and SB tended to be higher in the SB-BRS group when compared to the SB-DES group. CONCLUSION: Mid-term clinical outcomes following double-stenting using BRS were acceptable. Bifurcation lesions treated with DES in SB tended to have lower TLR rates in both the MB and SB when compared to implanting BRS in both branches. (c) 2016 Wiley Periodicals, Inc. PMID- 27184770 TI - The changing landscape of physiotherapy student clinical placements: An exploration of geographical distribution and student performance across settings. AB - OBJECTIVE: To describe the geographical distribution of physiotherapy clinical placements and investigate the relationship between geographical setting and clinical placement marks in physiotherapy students. DESIGN: A retrospective cohort design was used for this study. SETTING: The University of Newcastle, New South Wales. PARTICIPANTS: Data from entry-level Bachelor of Physiotherapy student clinical placements. MAIN OUTCOME MEASURE(S): Data from all clinical placements in the Physiotherapy program between 2003 and 2014 were included. For all clinical placements, student assessment mark, year of study, type of placement and placement location were collected. Placement location was then classified using the Modified Monash Model (MMM) categories: one (most metropolitan) to seven (most remote). RESULTS: Over the 12 year period of the study 3964 placements were completed. Between 2003 and 2005 the average proportion of clinical placements occurring in metropolitan areas (MMM1) was 78% and in rural areas (MMM categories 3-6) was 22%. In 2014 these proportions had changed to 59% (MMM1) and 40% (MMM3-6). There were significant differences in clinical placement grades between MMM1 and all other categories except MMM2, with lower assessment marks in MMM1 than other categories. CONCLUSIONS: The changing distribution of physiotherapy clinical placements may be reflective of increasing student numbers and greater efforts to support students completing rural and remote placements. This change may lead to a positive effect on the rural and remote physiotherapy workforce. Further research is required to determine the specific training and support needs of students and clinical educators in rural and remote settings. PMID- 27184771 TI - Psychiatric and Behavioural Disorders in Children with Epilepsy (ILAE Task Force Report): Subtle behavioural and cognitive manifestations of epilepsy in children. AB - A subtle behavioural or cognitive manifestation of epilepsy can be defined in two ways. First, epileptiform discharges not presenting as obvious seizures may nevertheless affect cognition and/or behaviour. Second, the actual seizures may be obvious but the way they affect cognition or behaviour may not be. There is a growing body of evidence indicating that the epileptiform discharges in benign epilepsy with centrotemporal spikes can affect behaviour and cognition. The focal discharges in other forms of epilepsy can also be associated with behavioural change. The Landau-Kleffner syndrome, the CSWS syndrome, transitory cognitive impairment and transient epileptic amnesia provide further examples of cognitive and behavioural manifestations resulting from subtle manifestations of the epilepsy. Prompt, effective antiepileptic treatment with medication or surgery can improve behaviour and cognition in at least some cases. PMID- 27184772 TI - A systematic review, evidence synthesis and meta-analysis of quantitative and qualitative studies evaluating the clinical effectiveness, the cost effectiveness, safety and acceptability of interventions to prevent postnatal depression. AB - BACKGROUND: Postnatal depression (PND) is a major depressive disorder in the year following childbirth, which impacts on women, their infants and their families. A range of interventions has been developed to prevent PND. OBJECTIVES: To (1) evaluate the clinical effectiveness, cost-effectiveness, acceptability and safety of antenatal and postnatal interventions for pregnant and postnatal women to prevent PND; (2) apply rigorous methods of systematic reviewing of quantitative and qualitative studies, evidence synthesis and decision-analytic modelling to evaluate the preventive impact on women, their infants and their families; and (3) estimate cost-effectiveness. DATA SOURCES: We searched MEDLINE, EMBASE, Science Citation Index and other databases (from inception to July 2013) in December 2012, and we were updated by electronic alerts until July 2013. REVIEW METHODS: Two reviewers independently screened titles and abstracts with consensus agreement. We undertook quality assessment. All universal, selective and indicated preventive interventions for pregnant women and women in the first 6 postnatal weeks were included. All outcomes were included, focusing on the Edinburgh Postnatal Depression Scale (EPDS), diagnostic instruments and infant outcomes. The quantitative evidence was synthesised using network meta-analyses (NMAs). A mathematical model was constructed to explore the cost-effectiveness of interventions contained within the NMA for EPDS values. RESULTS: From 3072 records identified, 122 papers (86 trials) were included in the quantitative review. From 2152 records, 56 papers (44 studies) were included in the qualitative review. The results were inconclusive. The most beneficial interventions appeared to be midwifery redesigned postnatal care [as shown by the mean 12-month EPDS score difference of -1.43 (95% credible interval -4.00 to 1.36)], person-centred approach (PCA)-based and cognitive-behavioural therapy (CBT)-based intervention (universal), interpersonal psychotherapy (IPT)-based intervention and education on preparing for parenting (selective), promoting parent-infant interaction, peer support, IPT-based intervention and PCA-based and CBT-based intervention (indicated). Women valued seeing the same health worker, the involvement of partners and access to several visits from a midwife or health visitor trained in person-centred or cognitive-behavioural approaches. The most cost-effective interventions were estimated to be midwifery redesigned postnatal care (universal), PCA-based intervention (indicated) and IPT-based intervention in the sensitivity analysis (indicated), although there was considerable uncertainty. Expected value of partial perfect information (EVPPI) for efficacy data was in excess of L150M for each population. Given the EVPPI values, future trials assessing the relative efficacies of promising interventions appears to represent value for money. LIMITATIONS: In the NMAs, some trials were omitted because they could not be connected to the main network of evidence or did not provide EPDS scores. This may have introduced reporting or selection bias. No adjustment was made for the lack of quality of some trials. Although we appraised a very large number of studies, much of the evidence was inconclusive. CONCLUSIONS: Interventions warrant replication within randomised controlled trials (RCTs). Several interventions appear to be cost-effective relative to usual care, but this is subject to considerable uncertainty. FUTURE WORK RECOMMENDATIONS: Several interventions appear to be cost-effective relative to usual care, but this is subject to considerable uncertainty. Future research conducting RCTs to establish which interventions are most clinically effective and cost-effective should be considered. STUDY REGISTRATION: This study is registered as PROSPERO CRD42012003273. FUNDING: The National Institute for Health Research Health Technology Assessment programme. PMID- 27184773 TI - Association of genetic variation in IKZF1, ARID5B, CDKN2A, and CEBPE with the risk of acute lymphoblastic leukemia in Tunisian children and their contribution to racial differences in leukemia incidence. AB - Recent genome-wide association studies (GWAS) focusing on pediatric acute lymphoblastic leukemia (ALL), the most common malignancy in children younger than 15 years old, have found evidence that single-nucleotide polymorphisms (SNPs) in IKZF1 (7p12.2), ARID5B (10q21.2), CDKN2A (9p21.3), and CEBPE (14q11.2) are strongly associated to the risk of developing pediatric ALL. These studies have been conducted in European and Thai populations, and it is unclear whether these observations generalize to other populations with a lower incidence of pediatric ALL. In order to explore the impact of these variants on pediatric ALL risk in the Tunisian population, we genotyped 58 cases of pediatric ALL and 150 controls for SNPs rs4132601 (7p12.2), rs7089424 (10q21.2), rs3731217 (9p21.3), and rs2239633 (14q11.2). Our results, which are consistent with findings in European populations, show that 3 SNPs, i.e., rs4132601 (P = .00116, odds ratio [OR] = 2.78, 95% confidence interval [CI] = [1.42, 5.87]), rs7089424 (P = .0022, OR = 0.49, 95% CI = [0.31, 0.79]), and rs2239633 (P = .0010, OR = 0.47, 95% CI = [0.29, 0.75]) are significantly associated with a higher risk of developing pediatric ALL (P < .05). Furthermore, we show differences in allele frequencies in SNPs between Tunisian and Caucasian and/or Thai populations (e.g., CEBPE, rs2239633; population attributable risk [PAR] ~15-fold the PAR of Thai population). These differences, combined with differences in linkage disequilibrium structure between populations and differences in size between populations, may contribute to racial differences in pediatric ALL incidence. PMID- 27184774 TI - Vascular endothelial growth factor expression in pediatric non-Hodgkin lymphoma: A prospective study. PMID- 27184775 TI - Factors influencing time to diagnosis and treatment among pediatric oncology patients in Kenya. AB - Early diagnosis and start of treatment are fundamental goals in cancer care. This study determines the time lag and the factors that influence the time to diagnosis and start of treatment. Study participants were parents of childhood cancer patients diagnosed between August 2013 and July 2014 in a hospital in Kenya. Patient, physician, diagnosis, treatment, health care system, and total delay were explored using a questionnaire. Demographic and medical data were collected from the patients' medical records. Parents of 99 childhood cancer patients were interviewed (response rate: 80%). Median total delay was 102 (9 1021) days. Median patient delay (4 days) was significantly shorter than health care system delay (median 87 days; P < .001). Diagnosis delay (median 94 days) was significantly longer than treatment delay (median 6 days; P < .001). days. Lack of health insurance at diagnosis and use of alternative medicine before attending conventional health services were associated with a significantly longer patient delay (P = .041 and P = .017, respectively). The type of cancer had a significant effect on treatment delay (P = .020). The type of health facility attended affected only patient delay (P = .03). Gender, age at diagnosis, stage of disease, parents' education level or income, and distance from hospital did not have a significant effect on the length of any type of delay. Training on childhood cancer should be included in the curricula for medical training institutes. In-service workshops should be held for the health workers already working. Families must be obligated to get health insurance. Families should be encourage to attend conventional health facilities and informed on symptoms of cancer through mass media. PMID- 27184776 TI - Rectal perforation: An unusual complication of uterine artery embolisation. PMID- 27184778 TI - A Disposable Planar Paper-Based Potentiometric Ion-Sensing Platform. AB - Ion-selective electrodes (ISEs) are widely used tools for fast and accurate ion sensing. Herein their design is simplified by embedding a potentiometric cell into paper, complete with an ISE, a reference electrode, and a paper-based microfluidic sample zone that offer the full function of a conventional ISE setup. The disposable planar paper-based ion-sensing platform is suitable for low cost point-of-care and in-field testing applications. The design is symmetrical and each interfacial potential within the cell is well defined and reproducible, so that the response of the device can be theoretically predicted. For a demonstration of clinical applications, paper-based Cl(-) and K(+) sensors are fabricated with highly reproducible and linear responses towards different concentrations of analyte ions in aqueous and biological samples. The single-use devices can be fabricated by a scalable method, do not need any pretreatment prior to use, and only require a sample volume of 20 MUL. PMID- 27184777 TI - From ScOOH to Sc2 O3 : Phase Control, Luminescent Properties, and Applications. AB - In the controlled synthesis of ScOOH nanomaterials, the surfactant molecule Na3 Cit not only helps to manipulate the crystallographic structures, but also to initiate the transfer from alpha-ScOOH to gamma-ScOOH. Further annealing of ScOOH generates cubic Sc2 O3 with morphologies inherited from respective origins. When doped with lanthanide ions, both ScOOH and Sc2 O3 can be utilized for high temperature probing and light-emitting-diode lighting. PMID- 27184779 TI - Plasma-Derived C1 Esterase Inhibitor for Acute Antibody-Mediated Rejection Following Kidney Transplantation: Results of a Randomized Double-Blind Placebo Controlled Pilot Study. AB - Antibody-mediated rejection (AMR) is typically treated with plasmapheresis (PP) and intravenous immunoglobulin (standard of care; SOC); however, there is an unmet need for more effective therapy. We report a phase 2b, multicenter double blind randomized placebo-controlled pilot study to evaluate the use of human plasma-derived C1 esterase inhibitor (C1 INH) as add-on therapy to SOC for AMR. Eighteen patients received 20 000 units of C1 INH or placebo (C1 INH n = 9, placebo n = 9) in divided doses every other day for 2 weeks. No discontinuations, graft losses, deaths, or study drug-related serious adverse events occurred. While the study's primary end point, a difference between groups in day 20 pathology or graft survival, was not achieved, the C1 INH group demonstrated a trend toward sustained improvement in renal function. Six-month biopsies performed in 14 subjects (C1 INH = 7, placebo = 7) showed no transplant glomerulopathy (TG) (PTC+cg>=1b) in the C1 INH group, whereas 3 of 7 placebo subjects had TG. Endogenous C1 INH measured before and after PP demonstrated decreased functional C1 INH serum concentration by 43.3% (p < 0.05) for both cohorts (C1 INH and placebo) associated with PP, although exogenous C1 INH treated patients achieved supraphysiological levels throughout. This new finding suggests that C1 INH replacement may be useful in the treatment of AMR. PMID- 27184780 TI - A Comparison of Mindray BC-6800, Sysmex XN-2000, and Beckman Coulter LH750 Automated Hematology Analyzers: A Pediatric Study. AB - BACKGROUND: Modern automated laboratory hematology analyzers allow the measurement of over 30 different hematological parameters useful in the diagnostic and clinical interpretation of patient symptoms. They use different methods to measure the same parameters. Thus, a comparison of complete blood count made by Mindray BC-6800, Sysmex XN-2000 and Beckman Coulter LH750 was performed. MATERIALS AND METHODS: A comparison of results obtained by automated analysis of 807 anticoagulated blood samples from children and 125 manual microscopic differentiations were performed. This comparative study included white blood cell count, red blood cell count, and erythrocyte indices, as well as platelet count. RESULTS: The present study showed a poor level of agreement between white blood cell enumeration and differentiation of the three automated hematology analyzers under comparison. A very good agreement was found when comparing manual blood smear and automated granulocytes, monocytes, and lymphocytes differentiation. Red blood cell evaluation showed better agreement than white blood cells between the studied analyzers. CONCLUSION: To conclude, studied instruments did not ensure satisfactory interchangeability and did not facilitate a substitution of one analyzer by another. PMID- 27184781 TI - Unprecedented selectivity in molecular recognition of carbohydrates by a metal organic framework. AB - Metal-organic framework (MOF) material NU-1000 adsorbs dimers cellobiose and lactose from aqueous solution, in amounts exceeding 1250 mg gNU-1000(-1) while completely excluding the adsorption of the monomer glucose, even in a competitive mode with cellobiose. The MOF also discriminates between dimers consisting of alpha and beta linkages, showing no adsorption of maltose. Electronic structure calculations demonstrate that key to this selective molecular recognition is the number of favorable CH-pi interactions made by the sugar with pyrene units of the MOF. PMID- 27184782 TI - Striatal dopamine D2/3 receptor availability increases after long-term bariatric surgery-induced weight loss. AB - In several studies reduced striatal dopamine D2/3 receptor (D2/3R) availability was reported in obese subjects compared to lean controls. Whether this is a reversible phenomenon remained uncertain. We previously determined the short-term effect of Roux-en-Y gastric bypass surgery (RYGB) on striatal D2/3R availability (using [(123)I]IBZM SPECT) in 20 morbidly obese women. Striatal D2/3R availability was lower compared to controls at baseline, and remained unaltered after 6 weeks, despite significant weight loss. To determine whether long-term bariatric surgery-induced weight loss normalizes striatal D2/3R binding, we repeated striatal D2/3R binding measurements at least 2 years after RYGB in 14 subjects of the original cohort. In addition, we assessed long-term changes in body composition, eating behavior and fasting plasma levels of leptin, ghrelin, insulin and glucose. Mean body mass index declined from 46+/-7kg/m(2) to 32+/ 6kg/m(2), which was accompanied by a significant increase in striatal D2/3R availability (p=0.031). Striatal D2/3R availability remained significantly reduced compared to the age-matched controls (BMI 22+/-2kg/m(2); p=0.01). Changes in striatal D2/3R availability did not correlate with changes in body weight/fat, insulin sensitivity, ghrelin or leptin levels. Scores on eating behavior questionnaires improved and changes in the General Food Craving Questionnaire State showed a borderline significant correlation with changes in striatal D2/3R availability. These findings show that striatal D2/3R availability increases after long-term bariatric-surgery induced weight loss, suggesting that reduced D2/3R availability in obesity is a reversible phenomenon. PMID- 27184783 TI - CINOEDV: a co-information based method for detecting and visualizing n-order epistatic interactions. AB - BACKGROUND: Detecting and visualizing nonlinear interaction effects of single nucleotide polymorphisms (SNPs) or epistatic interactions are important topics in bioinformatics since they play an important role in unraveling the mystery of "missing heritability". However, related studies are almost limited to pairwise epistatic interactions due to their methodological and computational challenges. RESULTS: We develop CINOEDV (Co-Information based N-Order Epistasis Detector and Visualizer) for the detection and visualization of epistatic interactions of their orders from 1 to n (n >= 2). CINOEDV is composed of two stages, namely, detecting stage and visualizing stage. In detecting stage, co-information based measures are employed to quantify association effects of n-order SNP combinations to the phenotype, and two types of search strategies are introduced to identify n order epistatic interactions: an exhaustive search and a particle swarm optimization based search. In visualizing stage, all detected n-order epistatic interactions are used to construct a hypergraph, where a real vertex represents the main effect of a SNP and a virtual vertex denotes the interaction effect of an n-order epistatic interaction. By deeply analyzing the constructed hypergraph, some hidden clues for better understanding the underlying genetic architecture of complex diseases could be revealed. CONCLUSIONS: Experiments of CINOEDV and its comparison with existing state-of-the-art methods are performed on both simulation data sets and a real data set of age-related macular degeneration. Results demonstrate that CINOEDV is promising in detecting and visualizing n order epistatic interactions. CINOEDV is implemented in R and is freely available from R CRAN: http://cran.r-project.org and https://sourceforge.net/projects/cinoedv/files/ . PMID- 27184784 TI - Cost-effectiveness of Wisconsin TEAM model for improving adherence and hypertension control in black patients. AB - OBJECTIVES: To assess the cost-effectiveness of the 6-month Team Education and Adherence Monitoring (TEAM) intervention for black patients with hypertension in community pharmacies using prospectively collected cost data. DESIGN: Cost effectiveness analysis of a cluster-randomized trial. SETTING: Twenty-eight chain pharmacies in 5 Wisconsin cities from December 2006 to February 2009. PARTICIPANTS: Five hundred seventy-six black patients with uncontrolled hypertension. INTERVENTION: Pharmacists and pharmacy technicians using novel tools for improving adherence and feedback to patients and physicians as compared to information-only control group. MAIN OUTCOME MEASURES: Incremental cost analysis of variable costs from the pharmacy perspective captured prospectively at the participant level. Outcomes (effect measures) were 6-month refill adherence, changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP), and proportion of patients achieving blood pressure (BP) control. RESULTS: Mean cost of intervention personnel time and tools was $104.8 +/- $45.2. Incremental variable costs per millimeter of mercury decrease in SBP and DBP were $22.2 +/- 16.3 and $66.0 +/- 228.4, respectively. The cost of helping 1 more person achieve the BP goal (<140/90 mm Hg) was $665.2 +/- 265.2; the cost of helping 1 more person achieve good refill adherence was $463.3 +/- 110.7. Prescription drug costs were higher for the TEAM group ($392.8 [SD = 396.3] versus $307.0 [SD = 295.2]; P = 0.02). The startup cost for pharmacy furniture, equipment, and privacy screen was $168 per pharmacy. CONCLUSION: Our randomized, practice-based intervention demonstrates that community pharmacists can implement a cost-effective intervention to improve hypertension control in blacks. This approach imposes a nominal expense at the pharmacy level that can be integrated into the ongoing pharmacist-patient relationship, and can enhance clinical and behavioral outcomes. PMID- 27184787 TI - [Adaptive and Maladaptive Strategies of Emotion Regulation in Adolescents with ADHD]. AB - The present study investigated differences between adolescents with ADHD and control subjects in their adaptive und maladaptive regulation of negative emotions. We assessed emotion regulation strategies using the German self-report questionnaire FEEL-KJ in a sample of adolescents (between 11 and 18 years) with ADHD (disturbance of activity, impulsivity and attention: n = 32, hyperkinetic conduct disorder: n = 26) and controls (n = 58). We found that adolescents with ADHD reported using less adaptive strategies for dealing with negative emotions than control subjects. No effects were found for maladaptive emotion regulation strategies for anger, fear and sadness. Our findings indicate that adolescents with ADHD should be encouraged in the development of adaptive emotion regulation. PMID- 27184785 TI - Consumer self-selection, safety, and compliance with a novel over-the-counter ibuprofen 600-mg immediate-release and extended-release tablet. AB - OBJECTIVE: The extent to which people comply with labeled instructions for use of long-acting over-the-counter analgesics is largely unknown; this study evaluated whether consumers can correctly select and use a new long-acting ibuprofen 600-mg immediate-release and extended-release (IR/ER) product. DESIGN: A single open label study with participants randomly assigned to 2 substudies. Self-selection substudy: participants estimated duration of their last pain episode, then selected ibuprofen IR/ER or standard ibuprofen IR for a similar episode. Compliance substudy: participants purchased and recorded real-world use of ibuprofen IR/ER in daily diaries over 30 days. SETTING: Eighteen U.S. pharmacies. PARTICIPANTS: Consumers age 12 years or older who used an average of >=5 doses per month of an over-the-counter analgesic in the past 3 months. INTERVENTION: Self-selection: questionnaire only. Compliance: ibuprofen IR/ER as needed. MAIN OUTCOME MEASURES: Self-selection: percentage who correctly selected or avoided selecting ibuprofen IR/ER based on anticipated pain duration. Compliance: proportion who were excessive users (use for >10 of 30 days and averaging >1600 mg/d, or >20 tablets over <=10 days and averaging >1600 mg/d). RESULTS: Self selection substudy (N = 249): on the primary endpoint, 69.1% (95% confidence interval [CI], 63.3%-74.8%) overall made a correct selection-63.5% (95% CI, 57.5% 69.4%) correctly selected ibuprofen IR/ER for pain >=6 hours and 5.6% (95% CI, 2.8%-8.5%) correctly avoided selecting ibuprofen IR/ER for shorter-lasting pain. Overall, 82.7% (95% CI, 77.6%-87.8%) chose correctly when subjects who picked ibuprofen IR for pain >=6 hours (a "missed opportunity," not an incorrect selection) were excluded. Compliance substudy (N = 405): only 5 participants (1.2%; 95% CI, 0.2%-2.3%) were excessive users; all took ibuprofen IR/ER for >10 days, averaging 1821 mg/day (range, 1661.5-2072.7 mg/d). No excessive user experienced an adverse event. CONCLUSION: Although the study did not meet the a priori primary efficacy outcome target, the majority of participants selected and used ibuprofen 600-mg IR/ER tablets correctly per the labeled instructions. PMID- 27184788 TI - [Effectiveness of an Educator Training about the Attention-Deficit-/Hyperactivity Disorder (ADHD)]. AB - The purpose of the current study was to examine the effectiveness of a workshop for teachers focussing on ADHD. A total of 44 educators answered a short version of the Knowledge of Attention Deficit Disorders Scale (KADDS) and self-report questions before, shortly after, and three month subsequent (follow-up) to a 2.5 hour long workshop. Results showed a significant increase in the educators' knowledge at post-test, which remained stable in the follow-up. Whereas uncertainties ("don't-know"-answers) decreased, heterogeneous results were found concerning the number of misconceptions. Educators upgraded their knowledge perception as well as their certainty in dealing with an affected child at post test. The results show that even a relatively short workshop had a positive and persistent impact on educators' ADHD expertise, which illustrates the potential of such workshops. PMID- 27184789 TI - [Changes in OPD-CA Axis Structure During Inpatient Psychodynamic Treatment of Adolescents Suffering from Comorbid Disorders of Conduct and Emotions]. AB - In a randomized controlled clinical trial (RCT) we evaluated an inpatient psychodynamic treatment for adolescents suffering from mixed disorders of conduct and emotions. The sample consisted of severely impaired adolescents with remarkable deficits regarding psychic structure. The current study wanted to examine if the manualized treatment did not only reduce symptoms but also enhance the structural level of the patients. The axis structure of the Operationalized Psychodynamic Diagnostics in Childhood and Adolescence (OPD-CA) was used to assess the structural level of N = 46 adolescent inpatients. To examine differences between the patients' structural level at the beginning and at the end of inpatient treatment we conducted a repeated measures ANOVA. The overall score as well as the three subscores of the axis structure improved significantly during inpatient treatment. The corresponding effect sizes were large (eta(2) = .29 to .47). The inpatient psychodynamic treatment led to significant improvements regarding symptomatology as well as psychic structure. However, further studies with larger sample size and control group data should be conducted to confirm these results. PMID- 27184790 TI - [Early Intervention and Cognitive Development: A Longitudinal Study with Psychologically Stressed Mother-Child-Dyad during Early Childhood]. AB - Early intervention programs aiming at developing parents' relationship and parenting skills and supporting young families have become increasingly established in Germany throughout the last decade. The present longitudinal study analyzed 53 children and their mothers receiving early intervention due to their psychosocially highly challenging life situations and personal circumstances. The children were examined at birth and at an age of twelve months as well as between ages two and four. The results revealed that the child's cognitive development could be predicted by both maternal sensitivity and mother's psychosocial stress. However, the amount, type, and intensity of early intervention did not have any effect on the child's development. In terms of the effectiveness of early interventions the results implicate that interventions seems to be offered in an unspecific manner and does not contribute to an improvement of the child's developmental status. PMID- 27184791 TI - [Multi-Family-Groups in Youth Welfare]. AB - Multi-Family-Groups are an intervention setting, that is mainly applied in the context of systemic therapy and counselling. In this article we introduce some basics of that setting and sketch some specifics and two examples of use for the application in the context of youth welfare. PMID- 27184795 TI - Lack of Sphingosine Causes Susceptibility to Pulmonary Staphylococcus Aureus Infections in Cystic Fibrosis. AB - BACKGROUND: Pulmonary Staphylococcus aureus (S. aureus) infections occur early in a high percentage of cystic fibrosis (CF) patients and it is believed that these infections facilitate further colonization of CF lungs with Pseudomonas aeruginosa (P. aeruginosa). Previous studies demonstrated a marked reduction of sphingosine in tracheal and bronchial epithelial cells in CF compared to wild type mice, while ceramide is massively increased in CF mice. METHODS: We investigated the effect of C18-sphingosine and C16-ceramide on S. aureus in vitro. Based on our results we performed pulmonary infections with S. aureus and tested the influence of sphingosine inhalation. RESULTS: In vitro incubation of S. aureus with C18-sphingosine rapidly killed S. aureus, while C16-ceramide did not affect bacterial survival, but abrogated the effect of C18-sphingosine when applied together. The in vivo infection experiments revealed a high susceptibility of CF mice to pulmonary infection with S. aureus. Inhalation of C18-sphingosine rescued CF mice from pulmonary infections with different clinical S. aureus isolates, including a methicillin-resistant S. aureus (MRSA) strain. CONCLUSIONS: Our data indicate that the imbalance between ceramide and sphingosine in the CF respiratory tract prevents killing of S. aureus and causes the high susceptibility of CF mice to pulmonary S. aureus infections. PMID- 27184796 TI - Effect of trauma onset on personality traits of politically persecuted victims. AB - BACKGROUND: The hypothesis that traumatic experiences in early childhood impact personality formation and psychopathology is well known in psychology and psychiatry, but this is difficult to verify statistically in methodological terms. The aim of this study, conducted with politically persecuted Poles, was to establish the influence of the time when trauma is experienced on the development of psychopathological symptoms. METHODS: The subjects were divided into two groups: those who had experienced trauma before age five (group 1) and those who experienced trauma at an older age (group 2). Subjects in both groups suffered from chronic untreated post-traumatic stress disorder. In order to test the research hypothesis, the Minnesota Multiphasic Personality Inventory-2 profiles of both groups were compared using Student's t-test, and the Mann-Whitney U-test. RESULTS: Statistically significant between-group differences were found for the F validity scale and the following clinical scales: Hypochondriasis, Depression, Psychopathic deviate, Psychasthenia, Schizophrenia, and Social introversion. All the significantly different scores were higher in the group traumatized in early childhood. People exposed to trauma under age five had profiles similar to those traumatized after age five, but they experienced their symptoms more intensely. CONCLUSIONS: Of clinical significance, higher scores on the psychasthenia, schizophrenia, and social introversion scales, especially on the psychopathic deviate scale, indicated pathology only in the early childhood trauma group. Taken together, these symptoms lead to withdrawal and hindrance of social functioning. This outcome confirms the hypothesis of the influence of various early childhood factors (such as trauma) on personality formation and personality traits in adulthood. PMID- 27184797 TI - HOXB13 expression in metastatic prostate cancer. PMID- 27184799 TI - NEDD 4 binding protein 2-like 1 promotes cancer cell invasion in oral squamous cell carcinoma. AB - Head and neck cancer, including oral squamous cell carcinoma, is the sixth most common cancer worldwide. Although cancer cell invasion and metastasis are crucial for tumor progression, detailed molecular mechanisms underlying the invasion and metastasis of oral squamous cell carcinoma are unclear. Comparison of transcriptional profiles using a cDNA microarray demonstrated that N4BP2L1, a novel oncogene expressed by neural precursor cells, is involved in oral squamous cell carcinoma. Expression of N4BP2L1 in oral squamous cell carcinoma is regulated by activation of miR-448 and is higher than in normal oral mucosa. Knockdown of N4BP2L1 and upregulation of miR-448 significantly reduced the invasive potential of oral squamous cell carcinoma cells. We studied N4BP2L1 expression in 187 cases of oral squamous cell carcinoma and found its overexpression to be significantly associated with nodal metastasis (P = 0.0155) and poor prognosis (P = 0.0136). Expression of miR-448 was found to be inversely associated with that of N4BP2L1 (P = 0.0019). Cox proportional hazards analysis identified N4BP2L1 expression as an independent predictor of disease-free survival (P = 0.0349). Our results suggest that N4BP2L1 plays an important role in tumor cell invasion in oral squamous cell carcinoma. Further studies on expression of N4BP2L1 may provide new insight into its function and clarify its potential as biomarker in human oral cancer. PMID- 27184798 TI - Overexpression of HIF1alpha and CAXI predicts poor outcome in early-stage triple negative breast cancer. AB - Dysregulated energy metabolism is one of the main mechanisms for uncontrolled growth in solid tumors. Hypoxia-inducible factor 1-alpha (HIF1alpha) is a transcription factor implicated in regulating several genes that are responsible for cell metabolism, including carbonic anhydrase IX (CAIX). The aim of this study is to determine the clinical significance of immunohistochemical metabolic alteration in early-stage triple negative breast cancer (TNBC) patients who received cyclophosphamide-based chemotherapy or radiotherapy and those with basal phenotype. Immunohistochemical staining for HIF1alpha and CAIX was performed to determine the correlation with clinicopathologic variables and survival outcome on tissue microarrays from 270 early-stage TNBC patients. In vitro experiments with multiple human TNBC cell lines, suppression of HIF1alpha by small interfering RNA (siRNA) significantly reduced CAIX protein expression in all cell lines. In multivariate analyses for different therapeutic modalities and basal phenotype, combined HIF1alpha and CAIX protein overexpression was significantly associated with disease-free survival in the total cohort (OR = 2.583, P = 0.002), stratified cohorts expressing basal phenotype (OR = 2.234, P = 0.021), and in those patients who received adjuvant chemotherapy (OR = 3.078, P = 0.023) and adjuvant radiotherapy (OR = 2.111, P = 0.050), respectively. In early TNBC, combined HIF1alpha and CAIX protein expression may serve as an unfavorable prognostic indicator particularly in patients treated with cyclophosphamide-based chemotherapy or radiotherapy as well as those with basal phenotype of breast cancer. PMID- 27184801 TI - Evaluation of the performances of six commercial kits designed for dengue NS1 and anti-dengue IgM, IgG and IgA detection in urine and saliva clinical specimens. AB - BACKGROUND: Rapid diagnostic tests (RDTs) have been commercialized in order to help physicians in dengue diagnosis. Until recently, only blood samples were used for those tests but it has been shown in several studies that urine and saliva can also be employed for dengue diagnosis. RDTs for the detection of NS1 antigen and anti-dengue IgG, IgM and IgA in urine and saliva specimens have thus been developed by Standard Diagnostics. The aim of this study was to evaluate the performances these new commercial assays. METHODS: Two panels of clinical specimens were used: one for the evaluation of the NS1-detection devices and the second for the evaluation of the antibody-detection kits. Each panel consisted of urine and saliva specimens collected sequentially from 86 patients with a confirmed dengue infection. A total of 291 saliva and 440 urine samples were included in the NS1-evaluation panel and 530 saliva and 528 urine specimens constituted the antibody-evaluation panel. All samples were tested in parallel by in-house ELISAs and by the commercial RDTs. RESULTS: The RDTs demonstrated an overall sensitivity of 15.5 %/27.9 %/10.7 % for NS1/IgG/IgA detection in urine samples and 20.4 %/ 34.8 %/11 %/6.2 % for NS1/IgG/IgM/IgA detection in saliva samples. Compared to the in-house NS1 ELISA, the results obtained with the NS1 RDT demonstrated a good correlation with urine samples (kappa coefficient: 0.88) but not with saliva specimens (kappa coefficient: 0.28). RDTs designed for antibody detection in saliva and urine were extremely specific (100 %), but less sensitive than the in-house ELISAs (i.e., reduction of the overall sensitivity by 12.2 % for the RDT designed for IgG detection in urine and by 23.7 % for the RDT detecting anti-DENV IgM in saliva). IgM were not detected in urine, either by RDT or ELISA. CONCLUSIONS: Although the RDTs evaluated here offer an apparently attractive approach for dengue diagnosis, this study suggests that these new commercial kits would require further improvement to increase the sensitivity. PMID- 27184800 TI - Metallothionein-1 as a biomarker of altered redox metabolism in hepatocellular carcinoma cells exposed to sorafenib. AB - BACKGROUND: Sorafenib, a kinase inhibitor active against various solid tumours, induces oxidative stress and ferroptosis, a new form of oxidative necrosis, in some cancer cells. Clinically-applicable biomarkers that reflect the impact of sorafenib on the redox metabolism of cancer cells are lacking. METHODS: We used gene expression microarrays, real-time PCR, immunoblot, protein-specific ELISA, and gene reporter constructs encoding the enzyme luciferase to study the response of a panel of cancer cells to sorafenib. Tumour explants prepared from surgical hepatocellular carcinoma (HCC) samples and serum samples obtained from HCC patients receiving sorafenib were also used. RESULTS: We observed that genes of the metallothionein-1 (MT1) family are induced in the HCC cell line Huh7 exposed to sorafenib. Sorafenib increased the expression of MT1G mRNA in a panel of human cancer cells, an effect that was not observed with eight other clinically approved kinase inhibitors. We identified the minimal region of the MT1G promoter that confers inducibility by sorafenib to a 133 base pair region containing an Anti-oxidant Response Element (ARE) and showed the essential role of the transcription factor NRF2 (Nuclear factor erythroid 2-Related Factor 2). We examined the clinical relevance of our findings by analysing the regulation of MT1G in five tumour explants prepared from surgical HCC samples. Finally, we showed that the protein levels of MT1 increase in the serum of some HCC patients receiving sorafenib, and found an association with reduced overall survival. CONCLUSION: These findings indicate that MT1 constitute a biomarker adapted for exploring the impact of sorafenib on the redox metabolism of cancer cells. PMID- 27184802 TI - Cost-effectiveness of medical primary prevention strategies to reduce absolute risk of cardiovascular disease in Tanzania: a Markov modelling study. AB - BACKGROUND: Cardiovascular disease (CVD) is a growing cause of mortality and morbidity in Tanzania, but contextualized evidence on cost-effective medical strategies to prevent it is scarce. We aim to perform a cost-effectiveness analysis of medical interventions for primary prevention of CVD using the World Health Organization's (WHO) absolute risk approach for four risk levels. METHODS: The cost-effectiveness analysis was performed from a societal perspective using two Markov decision models: CVD risk without diabetes and CVD risk with diabetes. Primary provider and patient costs were estimated using the ingredients approach and step-down methodologies. Epidemiological data and efficacy inputs were derived from systematic reviews and meta-analyses. We used disability- adjusted life years (DALYs) averted as the outcome measure. Sensitivity analyses were conducted to evaluate the robustness of the model results. RESULTS: For CVD low risk patients without diabetes, medical management is not cost-effective unless willingness to pay (WTP) is higher than US$1327 per DALY averted. For moderate risk patients, WTP must exceed US$164 per DALY before a combination of angiotensin converting enzyme inhibitor (ACEI) and diuretic (Diu) becomes cost effective, while for high-risk and very high-risk patients the thresholds are US$349 (ACEI, calcium channel blocker (CCB) and Diu) and US$498 per DALY (ACEI, CCB, Diu and Aspirin (ASA)) respectively. For patients with CVD risk with diabetes, a combination of sulfonylureas (Sulf), ACEI and CCB for low and moderate risk (incremental cost-effectiveness ratio (ICER) US$608 and US$115 per DALY respectively), is the most cost-effective, while adding biguanide (Big) to this combination yielded the most favourable ICERs of US$309 and US$350 per DALY for high and very high risk respectively. For the latter, ASA is also part of the combination. CONCLUSIONS: Medical preventive cardiology is very cost-effective for all risk levels except low CVD risk. Budget impact analyses and distributional concerns should be considered further to assess governments' ability and to whom these benefits will accrue. PMID- 27184803 TI - Course of Psychiatric Symptoms and Abstinence among Methamphetamine-Dependent Persons in Sober Living Recovery Homes. AB - BACKGROUND: Although studies of co-occurring psychiatric disorders among methamphetamine (MA)-dependent persons have been conducted in treatment programs, none have examined them in service settings used to sustain long-term recovery, such as sober living houses (SLHs). METHODS: Residents entering SLHs (N = 243) were interviewed within two weeks and at 6-, 12-, and 18-month follow-up. Measures assessed psychiatric symptoms using the Brief Symptom Inventory (BSI), past-year drug and alcohol dependence, and abstinence over six-month time periods. RESULTS: Overall, severity of psychiatric symptoms on the BSI was similar among MA-dependent and other dependent residents. Global psychiatric severity, depression, and somatization scales on the BSI predicted abstinence for both groups. However, phobic anxiety and hostility scales were associated with abstinence for MA-dependent residents but not for those dependent on other substances. CONCLUSION: The similarity of psychiatric symptoms among persons with and without MA dependence in SLHs is different from what studies have found in treatment programs. The association between psychiatric symptoms and abstinence for both groups suggests SLHs should consider provision of on- or off-site mental health services. Additional research is needed to understand why phobic anxiety and hostility are associated with abstinence among MA-dependent residents but not those dependent on other substances. PMID- 27184806 TI - Pattern of unintentional burns: A hospital based study from Pakistan. AB - BACKGROUND: Burns are major cause of morbidity and mortality in developing countries. Better understanding of the nature and extent of injury remains the major and only available way to halt the occurrence of the event. The present study was conducted to determine the prevalence of by self and by other unintentional burn, their comparison and the possible mode of acquisition by obtaining the history of exposure to known risk factors. METHODS: A cross sectional questionnaire based survey was conducted in Burns Centre of Civil Hospital Karachi, Pakistan and 324 hospitalized adult patients with unintentional burns were consecutively interviewed during August 2013 to February 2014. Information was collected on socio-demographic profile. The source of burn, affected body part and place of injury acquisition in terms of home, outside or work were also noted. Logistic regression model was conducted using SPSS software. RESULTS: Out of 324 patients, 295 (91%) had unintentional burn by self and 29 (9%) had unintentional burn by others. Male gender were 2.37 times and no schooling were 1.75 times more likely to have self-inflicted unintentional burn. Lower limb and head and neck were less likely to involve in unintentional burn by self. CONCLUSION: The burden of unintentional burn by self was considerably higher. Male gender and no schooling were found more at risk to have unintentional burn by self. PMID- 27184805 TI - Cardiac Strain in a Swine Model of Regional Hibernating Myocardium: Effects of CoQ10 on Contractile Reserve Following Bypass Surgery. AB - There is conflicting clinical evidence whether administration of coenzyme Q10 (CoQ10) improves function following coronary artery bypass graft surgery (CABG). Using a swine model of hibernating myocardium, we tested whether daily CoQ10 would improve contractile function by MRI at 4-week post-CABG. Twelve pigs underwent a thoracotomy and had a constrictor placed on the left anterior descending (LAD). At 12 weeks, they underwent off-pump bypass and received daily dietary supplements of either CoQ10 (10 mg/kg/day) or placebo. At 4-week post CABG, circumferential strain measurements in the hibernating LAD region from placebo and CoQ10 groups were not different and increased to a similar extent with dobutamine (-14.7 +/- 0.6 versus -14.8 +/- 0.1, respectively (NS)). Post sacrifice, oxidant stress markers were obtained in the mitochondrial isolates and protein carbonyl in the placebo, and CoQ10 groups were 6.14 +/- 0.36 and 5.05 +/- 0.32 nmol/mg, respectively (NS). In summary, CoQ10 did not improve contractile reserve or reduce oxidant stress at 4-week post-CABG. PMID- 27184807 TI - The need for effective literature searching for burns research: A timely reminder. PMID- 27184808 TI - Catheter ablation of idiopathic right ventricular arrhythmias in children with limited fluoroscopy. AB - INTRODUCTION: Definitive therapy of idiopathic right ventricular arrhythmias (VA) remains a challenge in interventional electrophysiology. The aim of this study was to evaluate the utility of EnSite Velocity system in the catheter ablation of RV tachycardia in children. METHODS: Thirty-five children with idiopathic right VA underwent catheter ablation procedure using the EnSite Velocity system guidance. RESULTS: The mean patient age was 12.0 +/- 3.7 years and the mean patient weight was 43.6 +/- 18.7 kg. The origin of right VA was divided into right ventricular outflow tract (RVOT) (30 patients) and other right ventricular localizations (five patients). The mean procedure and fluoroscopy times were 175 +/- 67 min and 2.35 +/- 1.89 min, respectively. No fluoroscopy was used in 19 patients. Acute success was achieved in 29 patients (83 %). The focus of VA was epicardial in three failed procedures. Cryocatheter (6-mm or 8-mm tip) was used in six patients, radiofrequency ablation (RFA) (4-mm or 8-mm tip) in 26 patients, and 4-mm tip irrigated RFA in three patients. During a mean follow-up of 15.9 +/- 7.1 months, ventricular tachycardia recurred in six patients (20 %). There were three complications (transient atrioventricular block developed in one patient during parahissian cryoablation and two patients developed transient complete right bundle branch block). CONCLUSIONS: Catheter ablation of idiopathic right VA in children can be performed safely and effectively with limited fluoroscopy using the EnSite Velocity system. PMID- 27184810 TI - Abstracts of the Medical Engineering and Bioinformatics 2016 (MEB 2016), China, 7 May 2016. PMID- 27184804 TI - Calcific Aortic Valve Disease: Part 2-Morphomechanical Abnormalities, Gene Reexpression, and Gender Effects on Ventricular Hypertrophy and Its Reversibility. AB - In part 1, we considered cytomolecular mechanisms underlying calcific aortic valve disease (CAVD), hemodynamics, and adaptive feedbacks controlling pathological left ventricular hypertrophy provoked by ensuing aortic valvular stenosis (AVS). In part 2, we survey diverse signal transduction pathways that precede cellular/molecular mechanisms controlling hypertrophic gene expression by activation of specific transcription factors that induce sarcomere replication in parallel. Such signaling pathways represent potential targets for therapeutic intervention and prevention of decompensation/failure. Hypertrophy provoking signals, in the form of dynamic stresses and ligand/effector molecules that bind to specific receptors to initiate the hypertrophy, are transcribed across the sarcolemma by several second messengers. They comprise intricate feedback mechanisms involving gene network cascades, specific signaling molecules encompassing G protein-coupled receptors and mechanotransducers, and myocardial stresses. Future multidisciplinary studies will characterize the adaptive/maladaptive nature of the AVS-induced hypertrophy, its gender- and individual patient-dependent peculiarities, and its response to surgical/medical interventions. They will herald more effective, precision medicine treatments. PMID- 27184809 TI - Left atrial posterior wall isolation: the icing on the cake. PMID- 27184813 TI - Parallel Polarization State Generation. AB - The control of polarization, an essential property of light, is of wide scientific and technological interest. The general problem of generating arbitrary time-varying states of polarization (SOP) has always been mathematically formulated by a series of linear transformations, i.e. a product of matrices, imposing a serial architecture. Here we show a parallel architecture described by a sum of matrices. The theory is experimentally demonstrated by modulating spatially-separated polarization components of a laser using a digital micromirror device that are subsequently beam combined. This method greatly expands the parameter space for engineering devices that control polarization. Consequently, performance characteristics, such as speed, stability, and spectral range, are entirely dictated by the technologies of optical intensity modulation, including absorption, reflection, emission, and scattering. This opens up important prospects for polarization state generation (PSG) with unique performance characteristics with applications in spectroscopic ellipsometry, spectropolarimetry, communications, imaging, and security. PMID- 27184811 TI - Androgen receptor variant-driven prostate cancer: clinical implications and therapeutic targeting. AB - While there are myriad mechanisms of primary and acquired resistance to conventional and next-generation hormonal therapies in prostate cancer, the potential role of androgen receptor splice variants (AR-Vs) has recently gained momentum. AR-Vs are abnormally truncated isoforms of the androgen receptor (AR) protein that lack the COOH-terminal domain but retain the NH2-terminal domain and DNA-binding domain and are thus constitutively active even in the absence of ligands. Although multiple preclinical studies have previously implicated AR-Vs in the development of castration resistance as well as resistance to abiraterone and enzalutamide, recent technological advances have made it possible to reliably detect and quantify AR-Vs from human clinical tumor specimens including blood samples. Initial clinical studies have now shown that certain AR-Vs, in particular AR-V7, may be associated with resistance to abiraterone and enzalutamide but not taxane chemotherapies when detected in circulating tumor cells. Efforts are now underway to clinically validate AR-V7 as a relevant treatment-selection biomarker in the context of other key genomic aberrations in men with metastatic castration-resistant prostate cancer. Additional efforts are underway to therapeutically target both AR and AR-Vs either directly or indirectly. Whether AR-Vs represent drivers of castration-resistant prostate cancer, or whether they are simply passenger events associated with aggressive disease or clonal heterogeneity, will ultimately be answered only through these types of clinical trials. PMID- 27184814 TI - Simulating the pitch sensitivity of twisted nematics of patchy rods. AB - Stiff, elongated biomolecules such as filamentous viruses, DNA or cellulose nanocrystals are known to form liquid crystals often exhibiting a helical supramolecular organization. Little is known about the microscopic origin, size and handedness of the helical pitch in these, so-called cholesteric phases. Experimental observations in chiral lyotropics suggest that long-ranged chiral forces of electrostatic origin acting between the mesogens are responsible for such organization. Using large-scale computer simulation we study the sensitivity of the pitch imparted by soft microscopic helices and confirm that the helical sense is sensitive to a change of packing fraction, magnitude of the molecular pitch and amplitude of the chiral interactions. In particular, we find evidence that the cholesteric helix sense may change spontaneously upon variation of particle density, at fixed molecular chirality. These pitch inversions have been reported in recent theoretical studies but simulation evidence remains elusive. We rationalize these sudden changes in the supramolecular helical symmetry on the basis of detailed measurements of the mean-torque generated by the twisting of the helices. The simulation methodology employed does not require confining the twisted nematic in a slab geometry and allows for a simultaneous measurement of the pitch and the twist elastic constant. We find that the twist elastic constant increases almost linearly with density suggesting that twisted nematic shows no signs of anomalous stiffening due to pre-smectic fluctuations at higher packing fraction. PMID- 27184812 TI - Further reduction of disqualification rates by additional MRI-targeted biopsy with transperineal saturation biopsy compared with standard 12-core systematic biopsies for the selection of prostate cancer patients for active surveillance. AB - BACKGROUND: Active surveillance (AS) is commonly based on standard 10-12-core prostate biopsies, which misclassify ~50% of cases compared with radical prostatectomy. We assessed the value of multiparametric magnetic resonance imaging (mpMRI)-targeted transperineal fusion-biopsies in men under AS. METHODS: In all, 149 low-risk prostate cancer (PC) patients were included in AS between 2010 and 2015. Forty-five patients were initially diagnosed by combined 24-core systematic transperineal saturation biopsy (SB) and MRI/transurethral ultrasound (TRUS)-fusion targeted lesion biopsy (TB). A total of 104 patients first underwent 12-core TRUS-biopsy. All patients were followed-up by combined SB and TB for restratification after 1 and 2 years. All mpMRI examinations were analyzed using PIRADS. AS was performed according to PRIAS-criteria and a NIH-nomogram for AS-disqualification was investigated. AS-disqualification rates for men initially diagnosed by standard or fusion biopsy were compared using Kaplan-Meier estimates and log-rank tests. Differences in detection rates of the SB and TB components were evaluated with a paired-sample analysis. Regression analyses were performed to predict AS-disqualification. RESULTS: A total of, 48.1% of patients diagnosed by 12-core TRUS-biopsy were disqualified from AS based on the MRI/TRUS-fusion biopsy results. In the initial fusion-biopsy cohort, upgrading occurred significantly less frequently during 2-year follow-up (20%, P<0.001). TBs alone were significantly superior compared with SBs alone to detect Gleason-score upgrading. NPV for Gleason-upgrading was 93.5% for PIRADS?2. PSA level, PSA density, NIH-nomogram, initial PIRADS score (P<0.001 each) and PIRADS-progression on consecutive MRI (P=0.007) were significant predictors of AS-disqualification. CONCLUSIONS: Standard TRUS-biopsies lead to significant underestimation of PC under AS. MRI/TRUS-fusion biopsies, and especially the TB component allow more reliable risk classification, leading to a significantly decreased chance of subsequent AS-disqualification. Cancer detection with mpMRI alone is not yet sensitive enough to omit SB on follow-up after initial 12-core TRUS-biopsy. After MRI/TRUS-fusion biopsy confirmed AS, it may be appropriate to biopsy only those men with suspected progression on MRI. PMID- 27184817 TI - Corrigendum to "Facilitatory effects of fetuin-A on atherosclerosis" [Atherosclerosis 246 (2016) 344-351]. PMID- 27184816 TI - Induction of C/EBP homologous protein-mediated apoptosis and autophagy by licochalcone A in non-small cell lung cancer cells. AB - Licochalcone A (LCA), a flavonoid isolated from the famous Chinese medicinal herb Glycyrrhiza uralensis Fisch, presents obvious anti-cancer effects. In this study, the anti-cancer effects and potential mechanisms of LCA in non-small cell lung cancer (NSCLC) cells were studied. LCA decreased cell viability, increased lactate dehydrogenase release, and induced apoptosis in a concentration-dependent manner in NSCLC cells while not in human embryonic lung fibroblast cells. The expression of phosphatidylethanolamine-modified microtubule-associated protein light-chain 3 (LC3-II) and formation of GFP-LC3 punta, two autophagic markers, were increased after treatment with LCA. LCA-induced LC3-II expression was increased when combined with chloroquine (CQ), while knock-down of autophagy related protein (ATG) 7 or ATG5 reversed LCA-induced LC3-II expression and GFP LC3 punta formation, suggesting that LCA induced autophagy in NSCLC cells. Inhibition of autophagy could not reverse the LCA-induced cell viability decrease and apoptosis. In addition, LCA increased the expression of endoplasmic reticulum stress related proteins, such as binding immunoglobulin protein and C/EBP homologous protein (CHOP). Knock-down of CHOP reversed LCA-induced cell viability decrease, apoptosis, and autophagy. Taken together, LCA-induced autophagic effect is an accompanied phenomenon in NSCLC cells, and CHOP is critical for LCA-induced cell viability decrease, apoptosis, and autophagy. PMID- 27184815 TI - A critical role for the Drosophila dopamine D1-like receptor Dop1R2 at the onset of metamorphosis. AB - BACKGROUND: Insect metamorphosis relies on temporal and spatial cues that are precisely controlled. Previous studies in Drosophila have shown that untimely activation of genes that are essential to metamorphosis results in growth defects, developmental delay and death. Multiple factors exist that safeguard these genes against dysregulated expression. The list of identified negative regulators that play such a role in Drosophila development continues to expand. RESULTS: By using RNAi transgene-induced gene silencing coupled to spatio/temporal assessment, we have unraveled an important role for the Drosophila dopamine 1-like receptor, Dop1R2, in development. We show that Dop1R2 knockdown leads to pre-adult lethality. In adults that escape death, abnormal wing expansion and/or melanization defects occur. Furthermore we show that salivary gland expression of this GPCR during the late larval/prepupal stage is essential for the flies to survive through adulthood. In addition to RNAi-induced effects, treatment of larvae with the high affinity D1-like receptor antagonist flupenthixol, also results in developmental arrest, and in morphological defects comparable to those seen in Dop1R2 RNAi flies. To examine the basis for pupal lethality in Dop1R2 RNAi flies, we carried out transcriptome analysis. These studies revealed up-regulation of genes that respond to ecdysone, regulate morphogenesis and/or modulate defense/immunity. CONCLUSION: Taken together our findings suggest a role for Dop1R2 in the repression of genes that coordinate metamorphosis. Premature release of this inhibition is not tolerated by the developing fly. PMID- 27184818 TI - A critical role for Piezo2 channels in the mechanotransduction of mouse proprioceptive neurons. AB - Proprioceptors are responsible for the conscious sensation of limb position and movement, muscle tension or force, and balance. Recent evidence suggests that Piezo2 is a low threshold mechanosensory receptor in the peripheral nervous system, acting as a transducer for touch sensation and proprioception. Thus, we characterized proprioceptive neurons in the mesencephalic trigeminal nucleus that are involved in processing proprioceptive information from the face and oral cavity. This is a specific population of neurons that produce rapidly adapting mechanically-activated currents that are fully dependent on Piezo2. As such, we analyzed the deficits in balance and coordination caused by the selective deletion of the channel in proprioceptors (conditional knockout). The data clearly shows that Piezo2 fulfills a critical role in a defined homogeneous population of proprioceptor neurons that innervate the head muscles, demonstrating that this ion channel is essential for mammalian proprioceptive mechanotransduction. PMID- 27184819 TI - Doxorubicin- and cisplatin-loaded nanostructured lipid carriers for breast cancer combination chemotherapy. AB - CONTEXT: Combination anticancer therapy is promising to generate synergistic anticancer effects, to maximize the treatment effect and to overcome multi-drug resistance. Nanostructured lipid carriers (NLCs), composed of solid and liquid lipids, and surfactants are potentially good colloidal drug carriers. OBJECTIVE: The aim of this study is to construct novel NLCs as nanocarriers for co-delivery of doxorubicin (DOX) and cisplatin (CDDP) to treat breast cancer. METHODS: DOX and CDDP loaded NLCs (D-C-NLCs) were prepared by the solvent diffusion method. The in vitro cytotoxicity and synergistic studies of different formulations were evaluated on human breast cancer cells (doxorubicin resistant) (MCF-7/ADR cells). In vivo anti-tumor effects were observed on the murine bearing MCF-7/ADR cells model. RESULTS: D-C-NLCs showed the highest cytotoxicity and synergistic effect of two drugs in tumor cells in vitro. The in vivo study revealed the greatest anti-tumor activity than the other formulations in the breast cancer model. CONCLUSION: The constructed NLCs could be used as a novel carrier for co-delivery of DOX and CDDP for breast cancer therapy. D-C-NLCs could be a promising targeted and combinational therapy nanomedicine. PMID- 27184820 TI - The impact of HENRY on parenting and family lifestyle: A national service evaluation of a preschool obesity prevention programme. AB - OBJECTIVES: One in five children in England are overweight/obese at school entry. Tackling obesity is therefore a priority. Right from the Start with HENRY is a widely-commissioned programme delivered by trained facilitators to small groups of parents over eight weekly sessions. It is designed to provide parents of infants and preschool children with the skills, knowledge and confidence required for a healthier family lifestyle. The aim of this work was to investigate programme impact using data collected routinely for quality control purposes. STUDY DESIGN: Analysis of routinely collected pre-post data from programmes delivered in the UK from January 2012 to February 2014. METHODS: Data were analysed from 144 programmes, including questionnaires relating to parenting, family eating behaviours, dietary intake, and physical activity/screen time. RESULTS: Over 24 months, 1100 parents attended programmes running in 86 locations. 788 (72%) completed >5 sessions of whom 624 (79%) provided baseline and completion questionnaires. Parents reported increases in healthiness of family lifestyle, parenting attributes, and emotional wellbeing following attendance (all P < .001). Both parents and children were reported to have increased their daily fruit/vegetable consumption, and reduced their consumption of high fat/sugar foods (both P < .001). There were also positive changes in eating behaviours, physical activity (P < .001) and children's screen time (P < .001). CONCLUSIONS: Significant changes were reported in all domains similar to those reported in a previous, smaller study in locations selected for experience and quality. The HENRY approach appears to have a beneficial impact even when delivered at scale in non-selected locations. Such changes, if maintained, may serve to protect against later obesity. PMID- 27184821 TI - Why is changing health-related behaviour so difficult? AB - OBJECTIVE: To demonstrate that six common errors made in attempts to change behaviour have prevented the implementation of the scientific evidence base derived from psychology and sociology; to suggest a new approach which incorporates recent developments in the behavioural sciences. STUDY DESIGN: The role of health behaviours in the origin of the current epidemic of non communicable disease is observed to have driven attempts to change behaviour. It is noted that most efforts to change health behaviours have had limited success. This paper suggests that in policy-making, discussions about behaviour change are subject to six common errors and that these errors have made the business of health-related behaviour change much more difficult than it needs to be. METHODS: Overview of policy and practice attempts to change health-related behaviour. RESULTS: The reasons why knowledge and learning about behaviour have made so little progress in alcohol, dietary and physical inactivity-related disease prevention are considered, and an alternative way of thinking about the behaviours involved is suggested. This model harnesses recent developments in the behavioural sciences. CONCLUSION: It is important to understand the conditions preceding behaviour psychologically and sociologically and to combine psychological ideas about the automatic and reflective systems with sociological ideas about social practice. PMID- 27184822 TI - Independent Association between Sleep Fragmentation and Dyslipidemia in Patients with Obstructive Sleep Apnea. AB - Obstructive sleep apnea (OSA) is independently associated with dyslipidemia. Previous studies have demonstrated that sleep fragmentation can impair lipid metabolism. The present study aimed to identify whether sleep fragmentation is independently associated with dyslipidemia, in a large-scale, clinic-based consecutive OSA sample. This cross-sectional study was conducted among 2,686 patients who underwent polysomnography (PSG) for suspicion of OSA from January 2008 to January 2013 at the sleep laboratory. Multivariate regression analyses were performed to evaluate the independent associations between the microarousal index (MAI) and lipid profiles adjusting for potential confounders, including metabolic syndrome components and nocturnal intermittent hypoxia. The adjusted odds ratios (ORs) for various types of dyslipidemia according to MAI quartiles, as determined by logistic regression were also evaluated. MAI was found positively associated with low-density lipoprotein cholesterol (LDL-c) but not with total cholesterol (TC), triglyceride (TG) or high-density lipoprotein cholesterol (HDL-c). Furthermore, the adjusted ORs (95% confidence interval) for hyper-LDL cholesterolemia increased across MAI quartiles, as follows: 1 (reference), 1.3 (1.1-1.7), 1.6 (1.2-2.0), and 1.6 (1.2-2.1) (p = 0.001, linear trend). Sleep fragmentation in OSA is independently associated with hyper-LDL cholesterolemia, which may predispose patients with OSA to a higher risk of cardiovascular disease. PMID- 27184825 TI - Retrospective study of the evolution of the incidence of non-traumatic lower extremity amputations (2007-2013) and risk factors of reamputation. AB - AIM: Describe the incidence of non-traumatic amputation in a Spain region and identify the risk factors associated with the level of amputation and reamputation. METHODS: Retrospective study on non-traumatic lower-extremity amputees in a Spanish region between 2007 and 2013. A descriptive, bivariate and multivariate analysis was performed using bivariate logistic regression. Statistical significance p<=0.05, SPSS V.21. RESULTS: 495 amputations were carried out in 353 patients. 81.0% (n=286) were men, mean age 68.7+/-10.8 years. The most frequent levels of amputation were digital (45.9%) and above-knee (40.5%). About 30% of the patients were reamputated. The multivariate analysis revealed that the factors independently related to the need for a minor lower extremity amputation were DM [OR 3.79 (CI 95% 2.0-7.27)], foot ulcer [OR 5.82 (CI 95% 2.24-15.11)] and previous ipsilateral amputation [OR 3.19 (CI 95% 1.21 8.42)]. The risk factors independently related to the need for reamputation were DM [OR 2.21 (CI95% 1.09-4.49)], smoking [OR 2.45 (CI95% 1.33-4.50)] and previous revascularization [OR 2.75 (CI95% 1.57-4.83)]. CONCLUSIONS: Determining the incidence of amputations in diabetic patients as an indicator of quality makes it possible for health services to be evaluated. In patients with DM the most common reamputations are minor and ipsilateral. PMID- 27184823 TI - A targeted immunomic approach identifies diagnostic antigens in the human pathogen Babesia microti. AB - BACKGROUND: Babesia microti is a protozoan parasite responsible for the majority of reported cases of human babesiosis and a major risk to the blood supply. Laboratory screening of blood donors may help prevent transfusion-transmitted babesiosis but there is no Food and Drug Administration-approved screening method yet available. Development of a sensitive, specific, and highly automated B. microti antibody assay for diagnosis of acute babesiosis and blood screening could have an important impact on decreasing the health burden of B. microti infection. STUDY DESIGN AND METHODS: Herein, we take advantage of recent advances in B. microti genomic analyses, field surveys of the reservoir host, and human studies in endemic areas to apply a targeted immunomic approach to the discovery of B. microti antigens that serve as signatures of active or past babesiosis infections. Of 19 glycosylphosphatidylinositol (GPI)-anchored protein candidates (BmGPI1-19) identified in the B. microti proteome, 17 were successfully expressed, printed on a microarray chip, and used to screen sera from uninfected and B. microti-infected mice and humans to determine immune responses that are associated with active and past infection. RESULTS: Antibody responses to various B. microti BmGPI antigens were detected and BmGPI12 was identified as the best biomarker of infection that provided high sensitivity and specificity when used in a microarray antibody assay. CONCLUSION: BmGPI12 alone or in combination with other BmGPI proteins is a promising candidate biomarker for detection of B. microti antibodies that might be useful in blood screening to prevent transfusion transmitted babesiosis. PMID- 27184826 TI - IgE-binding epitopes of various fish parvalbumins exist in a stereoscopic conformation maintained by Ca(2+) binding. PMID- 27184824 TI - Utilisation of emergency medical services for severe hypoglycaemia: An unrecognised health care burden. AB - AIMS: Diabetes is associated with several acute, life-threatening complications yet there are limited data on the utilisation of prehospital services for their management. This study aimed to examine the utilisation of emergency medical services (EMS) for prehospital hypoglycaemia, including patient characteristics and factors related to hospital transportation. METHODS: An observational study of patients requiring EMS for hypoglycaemia across Victoria, Australia over three years was conducted. Pre-specified data including patient demographics, comorbidities, examination findings and transport outcomes were obtained. Logistic regression was used to assess factors associated with transportation. RESULTS: During the study period, 12,411 hypoglycaemia events were attended by paramedics for people with diabetes. The majority were individuals with type 1 diabetes (58.8%), followed by type 2 diabetes (35.2%) and unspecified diabetes type (5.9%). Thirty-eight percent of patients were transported to hospital by EMS following hypoglycaemia. Factors associated with transport by EMS included extremes of age (<15 and >75years), female gender, type 2 diabetes, event at a nursing home or hospital/community clinic, presence of comorbidities and time of day. CONCLUSIONS: Examination of the utilisation of EMS for hypoglycaemia has identified a previously unquantified need for emergency care for people with diabetes as well as factors related to hospital transportation. PMID- 27184827 TI - Severe pneumonitis after nivolumab treatment in a patient with melanoma. PMID- 27184828 TI - Age Estimation in Living Egyptians Using Signal Joint T-cell Receptor Excision Circle Rearrangement. AB - Age estimation is one of the challenges in forensic sciences. There are many techniques to estimate the age. Molecular biology approach is one of these techniques. Signal joint T-cell receptor excision circles gene (sjTRECs), is one of this approach. We aimed to use sjTRECs as a suitable marker for age estimation among Egyptian population. TaqMan qPCR approach was used to quantify sjTREC levels in blood samples obtained from 153 healthy Egyptian individuals ranging from a few weeks to 70 years. Our results showed a significant negative correlation between sjTREC levels and age with p <= 0.05. Moreover, the individual's age can be determined through this formula Age = -30.671+ (-5.998Y) (Y is dCtTBP - sjTREC) with standard error +/-7.35 years. Within the forensic context, sjTREC' levels can be used to estimate the Egyptian individual's age accurately. PMID- 27184830 TI - Cyclic nucleotide phosphodiesterases in heart and vessels: A therapeutic perspective. AB - Cyclic nucleotide phosphodiesterases (PDEs) degrade the second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), thereby regulating multiple aspects of cardiac and vascular muscle functions. This highly diverse class of enzymes encoded by 21 genes encompasses 11 families that are not only responsible for the termination of cyclic nucleotide signalling, but are also involved in the generation of dynamic microdomains of cAMP and cGMP, controlling specific cell functions in response to various neurohormonal stimuli. In the myocardium and vascular smooth muscle, the PDE3 and PDE4 families predominate, degrading cAMP and thereby regulating cardiac excitation-contraction coupling and smooth muscle contractile tone. PDE3 inhibitors are positive inotropes and vasodilators in humans, but their use is limited to acute heart failure and intermittent claudication. PDE5 is particularly important for the degradation of cGMP in vascular smooth muscle, and PDE5 inhibitors are used to treat erectile dysfunction and pulmonary hypertension. There is experimental evidence that these PDEs, as well as other PDE families, including PDE1, PDE2 and PDE9, may play important roles in cardiac diseases, such as hypertrophy and heart failure, as well as several vascular diseases. After a brief presentation of the cyclic nucleotide pathways in cardiac and vascular cells, and the major characteristics of the PDE superfamily, this review will focus on the current use of PDE inhibitors in cardiovascular diseases, and the recent research developments that could lead to better exploitation of the therapeutic potential of these enzymes in the future. PMID- 27184831 TI - Percutaneous Transcatheter Treatment for Tricuspid Bioprosthesis Failure. AB - OBJECTIVES: To report procedural and 30-day outcomes following percutaneous transcatheter valve-in-valve (VIV) implantation for tricuspid bioprosthesis failure, with a new generation balloon-expandable transcatheter aortic valve implantation prosthesis. BACKGROUND: Severe tricuspid regurgitation is associated with a reduction in survival and increased morbidity. Many patients previously treated with tricuspid valve replacement require further intervention due to bioprosthesis failure. Surgical redo is the "gold standard" treatment however this is technically challenging and associated with significant risk. Percutaneous VIV intervention that is now well established in the management of aortic and mitral bioprosthesis failure may therefore be an alternative treatment option. METHODS: The study population consisted of all patients that underwent percutaneous transcatheter tricuspid VIV implantation for tricuspid bioprosthesis failure at the San Raffaele Scientific Institute, Milan, Italy. RESULTS: Five patients underwent successful transfemoral transcatheter tricuspid VIV implantation for bioprosthetic failure. One patient suffered acute kidney injury that was successfully medically managed. The remaining patients suffered no complications prior to hospital discharge. During 30-day follow-up, all patients reported a significant improvement in their functional status with normal valve function. Additionally, we observed an improvement in renal function (eGFR baseline 62.0 +/- 16.5 vs. follow-up 70.2 +/- 23.1 ml/min/m2 , P = 0.12) and improved hepatic congestion: bilirubin (1.47 +/- 0.8 vs. 1.01 +/- 0.7 mg/DL, P = 0.12), alanine aminotransferase (31.0 +/- 11.1 vs. 23.2 +/- 5.1 U/L, P = 0.11) and aspartate aminotransferase (35.8 +/- 6.3 vs. 29.8 +/- 13.6 U/L, P = 0.12). CONCLUSIONS: Transfemoral, transcatheter VIV treatment with a new generation balloon expandable devices appears to be a safe and efficacious treatment option for tricuspid bioprosthesis failure. (c) 2016 Wiley Periodicals, Inc. PMID- 27184829 TI - Genetic and neuroendocrine regulation of the postpartum brain. AB - Changes in expression of hundreds of genes occur during the production and function of the maternal brain that support a wide range of processes. In this review, we synthesize findings from four microarray studies of different maternal brain regions and identify a core group of 700 maternal genes that show significant expression changes across multiple regions. With those maternal genes, we provide new insights into reward-related pathways (maternal bonding), postpartum depression, social behaviors, mental health disorders, and nervous system plasticity/developmental events. We also integrate the new genes into well studied maternal signaling pathways, including those for prolactin, oxytocin/vasopressin, endogenous opioids, and steroid receptors (estradiol, progesterone, cortisol). A newer transcriptional regulation model for the maternal brain is provided that incorporates recent work on maternal microRNAs. We also compare the top 700 genes with other maternal gene expression studies. Together, we highlight new genes and new directions for studies on the postpartum brain. PMID- 27184832 TI - Expressions of SH3BP5, LMO3, and SNAP25 in diffuse large B-cell lymphoma cells and their association with clinical features. AB - Diffuse large B-cell lymphoma (DLBCL) is clinicopathologically and genetically heterogeneous with variable clinical outcomes. We previously identified signature genes overexpressed in CD5-positive (CD5(+) ) DLBCL, which is a poor prognostic subgroup of DLBCL. To elucidate the clinical significance of the protein expression of the signature genes overexpressed in CD5(+) DLBCL with regard to all DLBCL, not otherwise specified (NOS), 10 genes (SH3BP5, LMO3, SNAP25, SYT5, SV2C, CABP1, FGF1, FGFR2, NEUROD1, and SYN2) were selected and examined immunohistochemically with samples from 28 patients with DLBCL, NOS. Only three protein expressions, SH3BP5, LMO3, and SNAP25, were detected in DLBCL cells and then analyzed further with samples from 187 patients with DLBCL, NOS. The SH3BP5, LMO3, and SNAP25 proteins were expressed in 60% (103/173), 34% (59/175), and 46% (77/168) of DLBCL patients, respectively. These protein expressions were associated with CD5 expression, and only SH3BP5 was frequently expressed in activated B-cell-like DLBCL (P = 0.046). Compared to the SH3BP5-negative group, the SH3BP5(+) group was correlated with elderly onset (>60 years, P = 0.0096) and advanced-stage disease (stage III/IV, P = 0.037). The LMO3(+) group showed a worse performance status (>1, P = 0.0004). The SH3BP5(+) group and the LMO3(+) group had significantly worse overall survival than the negative groups (P = 0.030, 0.034; respectively) for the entire group. In a subgroup analysis of patients treated with rituximab-containing chemotherapy, there was no significant difference between groups. To the best of our knowledge, this is the first report showing the protein expressions of SH3BP5, LMO3, and SNAP25 in DLBCL cells and their clinical significance in patients with DLBCL. The SH3BP5 and LMO3 protein expressions are associated with the baseline clinical characteristics of DLBCL. PMID- 27184835 TI - Hyperfractionated radiation therapy in Burkitt's lymphoma: a reconsideration aspect. AB - Burkitt's lymphoma (BL) is an aggressive non-Hodgkin's B-cell lymphoma with an extremely short doubling time that often presents in extra nodal sites or as an acute leukaemia. Nowadays, with the rapid response to chemotherapy and the diffuse nature of BL, there is no established role for radiation therapy (RT) even in localized disease. Regarding the relapsed/refractory BL, the treatment recommendations remain undefined. We present a 56-year-old woman, diagnosed with BL refractory to 6 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone), who had disease progression on R-DHAP (rituximab, dexamethasone, high dose cytarabine and cisplatin) with intrathecal methotrexate, then a partial response on RICE (rituximab, ifosfamide, carboplatin and etoposide). Patient received high dose chemotherapy and autologous haematopoietic stem cell transplantation. Then, she was treated with hyperfractionated involved field RT regimen. Currently, the patient remains disease free for around 2 years after remission. We acknowledge that RT is not a standard treatment of BL, especially in patients who attain complete response (CR) after first-line multi agent chemotherapy or even in those who have a CR after second-line chemotherapy pre-transplant. Yet, the use of a superfractionated regimen of consolidative radiation could be justified in the treatment of recurrent/refractory localized BL who do not achieve a CR even with second-line salvage chemotherapy. Radiation therapy in this context, given that it is a well-tolerated treatment, is a modality worthy of being re-considered in relapsed/refractory BL. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27184834 TI - Spontaneous Patterning of High-Resolution Electronics via Parallel Vacuum Ultraviolet. AB - A spontaneous patterning technique via parallel vacuum ultraviolet is developed for fabricating large-scale, complex electronic circuits with 1 MUm resolution. The prepared organic thin-film transistors exhibit a low contact resistance of 1.5 kOmega cm, and high mobilities of 0.3 and 1.5 cm(2) V(-1) s(-1) in the devices with channel lengths of 1 and 5 MUm, respectively. PMID- 27184836 TI - Multiomic Analysis of the UV-Induced DNA Damage Response. AB - In order to facilitate the identification of factors and pathways in the cellular response to UV-induced DNA damage, several descriptive proteomic screens and a functional genomics screen were performed in parallel. Numerous factors could be identified with high confidence when the screen results were superimposed and interpreted together, incorporating biological knowledge. A searchable database, bioLOGIC, which provides access to relevant information about a protein or process of interest, was established to host the results and facilitate data mining. Besides uncovering roles in the DNA damage response for numerous proteins and complexes, including Integrator, Cohesin, PHF3, ASC-1, SCAF4, SCAF8, and SCAF11, we uncovered a role for the poorly studied, melanoma-associated serine/threonine kinase 19 (STK19). Besides effectively uncovering relevant factors, the multiomic approach also provides a systems-wide overview of the diverse cellular processes connected to the transcription-related DNA damage response. PMID- 27184837 TI - Autophagy Promotes Focal Adhesion Disassembly and Cell Motility of Metastatic Tumor Cells through the Direct Interaction of Paxillin with LC3. AB - Autophagy is a conserved catabolic process that plays a housekeeping role in eliminating protein aggregates and organelles and is activated during nutrient deprivation to generate metabolites and energy. Autophagy plays a significant role in tumorigenesis, although opposing context-dependent functions of autophagy in cancer have complicated efforts to target autophagy for therapeutic purposes. We demonstrate that autophagy inhibition reduces tumor cell migration and invasion in vitro and attenuates metastasis in vivo. Numerous abnormally large focal adhesions (FAs) accumulate in autophagy-deficient tumor cells, reflecting a role for autophagy in FA disassembly through targeted degradation of paxillin. We demonstrate that paxillin interacts with processed LC3 through a conserved LIR motif in the amino-terminal end of paxillin and that this interaction is regulated by oncogenic SRC activity. Together, these data establish a function for autophagy in FA turnover, tumor cell motility, and metastasis. PMID- 27184839 TI - Persistent Alterations in Microglial Enhancers in a Model of Chronic Pain. AB - Chronic pain is a common and devastating condition that induces well characterized changes in neurons and microglia. One major unanswered question is why these changes should persist long after the precipitating injury has healed. Here, we suggest that some of the longer-lasting consequences of nerve injury may be hidden in the epigenome. Cell sorting and sequencing techniques were used to characterize the spinal cord immune response in a mouse model of chronic neuropathic pain. Infiltration of peripheral myeloid cells was found to be absent, and RNA sequencing (RNA-seq) of central microglia revealed transient gene expression changes in response to nerve ligation. Conversely, examination of microglial enhancers revealed persistent, post-injury alterations in close proximity to transcriptionally regulated genes. Enhancers are regions of open chromatin that define a cell's transcription factor binding profile. We hypothesize that changes at enhancers may constitute a mechanism by which painful experiences are recorded at a molecular level. PMID- 27184838 TI - The Drosophila Dicer-1 Partner Loquacious Enhances miRNA Processing from Hairpins with Unstable Structures at the Dicing Site. AB - In Drosophila, Dicer-1 binds Loquacious-PB (Loqs-PB) as its major co-factor. Previous analyses indicated that loqs mutants only partially impede miRNA processing, but the activity of minor isoforms or maternally deposited Loqs was not eliminated in these studies. We addressed this by generating a cell line from loqs-null embryos and found that only ~40% of miRNAs showed clear Loqs dependence. Genome-wide comparison of the hairpin structure and Loqs dependence suggested that Loqs substrates are influenced by base-pairing status at the dicing site. Artificial alteration of base-pairing stability at this position in model miRNA hairpins resulted in predicted changes in Loqs dependence, providing evidence for this hypothesis. Finally, we found that evolutionarily young miRNA genes tended to be Loqs dependent. We propose that Loqs may have roles in assisting the de novo emergence of miRNA genes by facilitating dicing of suboptimal hairpin substrates. PMID- 27184840 TI - Glycosaminoglycan Profiling in Patients' Plasma and Urine Predicts the Occurrence of Metastatic Clear Cell Renal Cell Carcinoma. AB - Metabolic reprogramming is a hallmark of clear cell renal cell carcinoma (ccRCC) progression. Here, we used genome-scale metabolic modeling to elucidate metabolic reprogramming in 481 ccRCC samples and discovered strongly coordinated regulation of glycosaminoglycan (GAG) biosynthesis at the transcript and protein levels. Extracellular GAGs are implicated in metastasis, so we speculated that such regulation might translate into a non-invasive biomarker for metastatic ccRCC (mccRCC). We measured 18 GAG properties in 34 mccRCC samples versus 16 healthy plasma and/or urine samples. The GAG profiles were distinctively altered in mccRCC. We derived three GAG scores that distinguished mccRCC patients with 93.1% 100% accuracy. We validated the score accuracies in an independent cohort (up to 18 mccRCC versus nine healthy) and verified that the scores normalized in eight patients with no evidence of disease. In conclusion, coordinated regulation of GAG biosynthesis occurs in ccRCC, and non-invasive GAG profiling is suitable for mccRCC diagnosis. PMID- 27184841 TI - Tet Enzymes Regulate Telomere Maintenance and Chromosomal Stability of Mouse ESCs. AB - Ten-eleven translocation (Tet) family proteins convert 5-methylcytosine to 5 hydroxymethylcytosine. We show that mouse embryonic stem cells (ESCs) depleted of Tet1 and/or Tet2 by RNAi exhibit short telomeres and chromosomal instability, concomitant with reduced telomere recombination. Tet1 and Tet2 double-knockout ESCs also display short telomeres but to a lesser extent. Notably, Tet1/2/3 triple-knockout ESCs show heterogeneous telomere lengths and increased frequency of telomere loss and chromosomal fusion. Mechanistically, Tets depletion or deficiency increases Dnmt3b and decreases 5hmC levels, resulting in elevated methylation levels at sub-telomeres. Consistently, knockdown of Dnmt3b or addition of 2i (MAPK and GSK3beta inhibitors), which also inhibits Dnmt3b, reduces telomere shortening, partially rescuing Tet1/2 deficiency. Interestingly, Tet1/2 double or Tet1/2/3 triple knockout in ESCs consistently upregulates Zscan4, which may counteract telomere shortening. Together, Tet enzymes play important roles in telomere maintenance and chromosomal stability of ESCs by modulating sub-telomeric methylation levels. PMID- 27184842 TI - The RNA Binding Protein IMP2 Preserves Glioblastoma Stem Cells by Preventing let 7 Target Gene Silencing. AB - Cancer stem cells (CSCs) can drive tumor growth, and their maintenance may rely on post-transcriptional regulation of gene expression, including that mediated by microRNAs (miRNAs). The let-7 miRNA family has been shown to induce differentiation by silencing stem cell programs. Let-7-mediated target gene suppression is prevented by LIN28A/B, which reduce let-7 biogenesis in normal embryonic and some cancer stem cells and ensure maintenance of stemness. Here, we find that glioblastoma stem cells (GSCs) lack LIN28 and express both let-7 and their target genes, suggesting LIN28-independent protection from let-7 silencing. Using photoactivatable-ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP), we show that insulin-like growth factor 2 mRNA binding protein 2 (IMP2) binds to let-7 miRNA recognition elements (MREs) and prevents let-7 target gene silencing. Our observations define the RNA-binding repertoire of IMP2 and identify a mechanism whereby it supports GSC and neural stem cell specification. PMID- 27184843 TI - Centromeric Transcription Regulates Aurora-B Localization and Activation. AB - Centromeric transcription is widely conserved; however, it is not clear what role centromere transcription plays during mitosis. Here, I find that centromeres are transcribed in Xenopus egg extracts into a long noncoding RNA (lncRNA; cen-RNA) that localizes to mitotic centromeres, chromatin, and spindles. cen-RNAs bind to the chromosomal passenger complex (CPC) in vitro and in vivo. Blocking transcription or antisense inhibition of cen-RNA leads to a reduction of CPC localization to the inner centromere and misregulation of CPC component Aurora-B activation independently of known centromere recruitment pathways. Additionally, transcription is required for normal bipolar attachment of kinetochores to the mitotic spindle, consistent with a role for cen-RNA in CPC regulation. This work demonstrates that cen-RNAs promote normal kinetochore function through regulation of the localization and activation of the CPC and confirm that lncRNAs are components of the centromere. PMID- 27184844 TI - An Evolutionarily Conserved PLC-PKD-TFEB Pathway for Host Defense. AB - The mechanisms that tightly control the transcription of host defense genes have not been fully elucidated. We previously identified TFEB as a transcription factor important for host defense, but the mechanisms that regulate TFEB during infection remained unknown. Here, we used C. elegans to discover a pathway that activates TFEB during infection. Gene dkf-1, which encodes a homolog of protein kinase D (PKD), was required for TFEB activation in nematodes infected with Staphylococcus aureus. Conversely, pharmacological activation of PKD was sufficient to activate TFEB. Furthermore, phospholipase C (PLC) gene plc-1 was also required for TFEB activation, downstream of Galphaq homolog egl-30 and upstream of dkf-1. Using reverse and chemical genetics, we discovered a similar PLC-PKD-TFEB axis in Salmonella-infected mouse macrophages. In addition, PKCalpha was required in macrophages. These observations reveal a previously unknown host defense signaling pathway, which has been conserved across one billion years of evolution. PMID- 27184845 TI - PDK1 Is a Regulator of Epidermal Differentiation that Activates and Organizes Asymmetric Cell Division. AB - Asymmetric cell division (ACD) in a perpendicular orientation promotes cell differentiation and organizes the stratified epithelium. However, the upstream cues regulating ACD have not been identified. Here, we report that phosphoinositide-dependent kinase 1 (PDK1) plays a critical role in establishing ACD in the epithelium. Production of phosphatidyl inositol triphosphate (PIP3) is localized to the apical side of basal cells. Asymmetric recruitment of atypical protein kinase C (aPKC) and partitioning defective (PAR) 3 is impaired in PDK1 conditional knockout (CKO) epidermis. PDK1(CKO) keratinocytes do not undergo calcium-induced activation of aPKC or IGF1-induced activation of AKT and fail to differentiate. PDK1(CKO) epidermis shows decreased expression of Notch, a downstream effector of ACD, and restoration of Notch rescues defective expression of differentiation-induced Notch targets in vitro. We therefore propose that PDK1 signaling regulates the basal-to-suprabasal switch in developing epidermis by acting as both an activator and organizer of ACD and the Notch-dependent differentiation program. PMID- 27184847 TI - APEX Fingerprinting Reveals the Subcellular Localization of Proteins of Interest. AB - Deciphering the sub-compartmental location of a given protein of interest may help explain its physiological function, but it can be challenging to do using optical or biochemical methods. Imaging with electron microscopy (EM) can provide highly resolved mapping of proteins; however, EM requires complex sample preparation and a specialized facility. Here, we use engineered ascorbate peroxidase (APEX)-generated molecular labeling patterns to provide information regarding intracellular microenvironments in living cells. Using APEX labeling of specific proteins, we uncovered subcellular localization at sub-compartmental resolution and successfully elucidated the membrane protein topology of HMOX1 and sub-mitochondrial localization of recently identified mitochondrial proteins. This method can be expanded to confirm sub-mitochondrial localization and membrane topologies of previously identified mitochondrial proteins. PMID- 27184849 TI - Programming of Intestinal Epithelial Differentiation by IL-33 Derived from Pericryptal Fibroblasts in Response to Systemic Infection. AB - The intestinal epithelium constitutes an efficient barrier against the microbial flora. Here, we demonstrate an unexpected function of IL-33 as a regulator of epithelial barrier functions. Mice lacking IL-33 showed decreased Paneth cell numbers and lethal systemic infection in response to Salmonella typhimurium. IL 33 was produced upon microbial challenge by a distinct population of pericryptal fibroblasts neighboring the intestinal stem cell niche. IL-33 programmed the differentiation of epithelial progenitors toward secretory IEC including Paneth and goblet cells. Finally, IL-33 suppressed Notch signaling in epithelial cells and induced expression of transcription factors governing differentiation into secretory IEC. In summary, we demonstrate that gut pericryptal fibroblasts release IL-33 to translate bacterial infection into an epithelial response to promote antimicrobial defense. PMID- 27184846 TI - MCUR1 Is a Scaffold Factor for the MCU Complex Function and Promotes Mitochondrial Bioenergetics. AB - Mitochondrial Ca(2+) Uniporter (MCU)-dependent mitochondrial Ca(2+) uptake is the primary mechanism for increasing matrix Ca(2+) in most cell types. However, a limited understanding of the MCU complex assembly impedes the comprehension of the precise mechanisms underlying MCU activity. Here, we report that mouse cardiomyocytes and endothelial cells lacking MCU regulator 1 (MCUR1) have severely impaired [Ca(2+)]m uptake and IMCU current. MCUR1 binds to MCU and EMRE and function as a scaffold factor. Our protein binding analyses identified the minimal, highly conserved regions of coiled-coil domain of both MCU and MCUR1 that are necessary for heterooligomeric complex formation. Loss of MCUR1 perturbed MCU heterooligomeric complex and functions as a scaffold factor for the assembly of MCU complex. Vascular endothelial deletion of MCU and MCUR1 impaired mitochondrial bioenergetics, cell proliferation, and migration but elicited autophagy. These studies establish the existence of a MCU complex that assembles at the mitochondrial integral membrane and regulates Ca(2+)-dependent mitochondrial metabolism. PMID- 27184850 TI - The Adhesion G Protein-Coupled Receptor GPR56/ADGRG1 Is an Inhibitory Receptor on Human NK Cells. AB - Natural killer (NK) cells possess potent cytotoxic mechanisms that need to be tightly controlled. Here, we explored the regulation and function of GPR56/ADGRG1, an adhesion G protein-coupled receptor implicated in developmental processes and expressed distinctively in mature NK cells. Expression of GPR56 was triggered by Hobit (a homolog of Blimp-1 in T cells) and declined upon cell activation. Through studying NK cells from polymicrogyria patients with disease causing mutations in ADGRG1, encoding GPR56, and NK-92 cells ectopically expressing the receptor, we found that GPR56 negatively regulates immediate effector functions, including production of inflammatory cytokines and cytolytic proteins, degranulation, and target cell killing. GPR56 pursues this activity by associating with the tetraspanin CD81. We conclude that GPR56 inhibits natural cytotoxicity of human NK cells. PMID- 27184848 TI - Impaired Mitochondrial Fat Oxidation Induces FGF21 in Muscle. AB - Fatty acids are the primary fuel source for skeletal muscle during most of our daily activities, and impaired fatty acid oxidation (FAO) is associated with insulin resistance. We have developed a mouse model of impaired FAO by deleting carnitine palmitoyltransferase-1b specifically in skeletal muscle (Cpt1b(m-/-)). Cpt1b(m-/-) mice have increased glucose utilization and are resistant to diet induced obesity. Here, we show that inhibition of mitochondrial FAO induces FGF21 expression specifically in skeletal muscle. The induction of FGF21 in Cpt1b deficient muscle is dependent on AMPK and Akt1 signaling but independent of the stress signaling pathways. FGF21 appears to act in a paracrine manner to increase glucose uptake under low insulin conditions, but it does not contribute to the resistance to diet-induced obesity. PMID- 27184851 TI - Transplantation Dose Alters the Differentiation Program of Hematopoietic Stem Cells. AB - Hematopoietic stem cell (HSC) transplantation is the most prevalent stem cell therapy, but it remains a risky procedure. To improve this treatment, it is important to understand how transplanted stem cells rebuild the blood and immune systems and how this process is impacted by transplantation variables such as the HSC dose. Here, we find that, in the long term following transplantation, 70%-80% of donor-HSC-derived clones do not produce all measured blood cell types. High HSC doses lead to more clones that exhibit balanced lymphocyte production, whereas low doses produce more T-cell-specialized clones. High HSC doses also produce significantly higher proportions of early-differentiating clones compared to low doses. These complex differentiation behaviors uncover the clonal-level regeneration dynamics of hematopoietic regeneration and suggest that transplantation dose can be exploited to improve stem cell therapy. PMID- 27184853 TI - Translational Capacity of a Cell Is Determined during Transcription Elongation via the Ccr4-Not Complex. AB - The current understanding of gene expression considers transcription and translation to be independent processes. Challenging this notion, we found that translation efficiency is determined during transcription elongation through the imprinting of mRNAs with Not1, the central scaffold of the Ccr4-Not complex. We determined that another subunit of the complex, Not5, defines Not1 binding to specific mRNAs, particularly those produced from ribosomal protein genes. This imprinting mechanism specifically regulates ribosomal protein gene expression, which in turn determines the translational capacity of cells. We validate our model by SILAC and polysome profiling experiments. As a proof of concept, we demonstrate that enhanced translation compensates for transcriptional elongation stress. Taken together, our data indicate that in addition to defining mRNA stability, components of the Ccr4-Not imprinting complex regulate RNA translatability, thus ensuring global gene expression homeostasis. PMID- 27184854 TI - TREX1 Knockdown Induces an Interferon Response to HIV that Delays Viral Infection in Humanized Mice. AB - Despite their antiviral effect, the in vivo effect of interferons on HIV transmission is difficult to predict, because interferons also activate and recruit HIV-susceptible cells to sites of infection. HIV does not normally induce type I interferons in infected cells, but does if TREX1 is knocked down. Here, we investigated the effect of topical TREX1 knockdown and local interferon production on HIV transmission in human cervicovaginal explants and humanized mice. In explants in which TREX1 was knocked down, HIV induced interferons, which blocked infection. In humanized mice, even though TREX1 knockdown increased infiltrating immune cells, it delayed viral replication for 3-4 weeks. Similarly intravaginal application of type I interferons the day before HIV infection induced interferon responsive genes, reduced inflammation, and decreased viral replication. However, intravenous interferon enhanced inflammation and infection. Thus, in models of human sexual transmission, a localized interferon response inhibits HIV transmission but systemic interferons do not. PMID- 27184855 TI - TFG Promotes Organization of Transitional ER and Efficient Collagen Secretion. AB - Collagen is the most abundant protein in the animal kingdom. It is of fundamental importance during development for cell differentiation and tissue morphogenesis as well as in pathological processes such as fibrosis and cancer cell migration. However, our understanding of the mechanisms of procollagen secretion remains limited. Here, we show that TFG organizes transitional ER (tER) and ER exit sites (ERESs) into larger structures. Depletion of TFG results in dispersion of tER elements that remain associated with individual ER-Golgi intermediate compartments (ERGICs) as largely functional ERESs. We show that TFG is not required for the transport and packaging of small soluble cargoes but is necessary for the export of procollagen from the ER. Our work therefore suggests a key relationship between the structure and function of ERESs and a central role for TFG in optimizing COPII assembly for procollagen export. PMID- 27184852 TI - Mitochondrial H2O2 in Lung Antigen-Presenting Cells Blocks NF-kappaB Activation to Prevent Unwarranted Immune Activation. AB - Inhalation of environmental antigens such as allergens does not always induce inflammation in the respiratory tract. While antigen-presenting cells (APCs), including dendritic cells and macrophages, take up inhaled antigens, the cell intrinsic molecular mechanisms that prevent an inflammatory response during this process, such as activation of the transcription factor NF-kappaB, are not well understood. Here, we show that the nuclear receptor PPARgamma plays a critical role in blocking NF-kappaB activation in response to inhaled antigens to preserve immune tolerance. Tolerance induction promoted mitochondrial respiration, generation of H2O2, and suppression of NF-kappaB activation in WT, but not PPARgamma-deficient, APCs. Forced restoration of H2O2 in PPARgamma-deficient cells suppressed IkappaBalpha degradation and NF-kappaB activation. Conversely, scavenging reactive oxygen species from mitochondria promoted IkappaBalpha degradation with loss of regulatory and promotion of inflammatory T cell responses in vivo. Thus, communication between PPARgamma and the mitochondria maintains immune quiescence in the airways. PMID- 27184857 TI - Gene expression analysis in airway-secreting extracellular vesicles upon house dust mite exposure. PMID- 27184856 TI - Oncology Patient Perceptions of the Use of Ionizing Radiation in Diagnostic Imaging. AB - PURPOSE: To measure the knowledge of oncology patients regarding use and potential risks of ionizing radiation in diagnostic imaging. METHODS: A 30 question survey was developed and e-mailed to 48,736 randomly selected patients who had undergone a diagnostic imaging study at a comprehensive cancer center between November 1, 2013 and January 31, 2014. The survey was designed to measure patients' knowledge about use of ionizing radiation in diagnostic imaging and attitudes about radiation. Nonresponse bias was quantified by sending an abbreviated survey to patients who did not respond to the original survey. RESULTS: Of the 48,736 individuals who were sent the initial survey, 9,098 (18.7%) opened it, and 5,462 (11.2%) completed it. A total of 21.7% of respondents reported knowing the definition of ionizing radiation; 35.1% stated correctly that CT used ionizing radiation; and 29.4% stated incorrectly that MRI used ionizing radiation. Many respondents did not understand risks from exposure to diagnostic doses of ionizing radiation: Of 3,139 respondents who believed that an abdominopelvic CT scan carried risk, 1,283 (40.9%) believed sterility was a risk; 669 (21.3%) believed heritable mutations were a risk; 657 (20.9%) believed acute radiation sickness was a risk; and 135 (4.3%) believed cataracts were a risk. CONCLUSIONS: Most patients and caregivers do not possess basic knowledge regarding the use of ionizing radiation in oncologic diagnostic imaging. To ensure health literacy and high-quality patient decision making, efforts to educate patients and caregivers should be increased. Such education might begin with information about effects that are not risks of diagnostic imaging. PMID- 27184858 TI - Human immune deficiency virus (HIV) infection during pregnancy at Gadarif hospital, Eastern Sudan. AB - This was a prospective study conducted on all pregnant and parturient women attending Gadarif Maternity Hospital, Sudan from January 2009 to December 2013 to investigate the maternal characteristics, pregnancy outcomes and estimate of maternal to child transmission of HIV among HIV infected women. During the study period, there were 26 HIV positive mothers among 6420 tested women yielding an incidence rate of 0.4%. The majority of these 26 infected women were of urban residence (69.2%), presented with normal CD4+ T cell count; ? 350?cu. mm3 (96.2%), had less than secondary education (57.7%) and housewives (84.6%). The mean age (SD) was significantly varied between the sero-positive and sero negative women, 25.9 (5.7) vs. 36.1 (5.7), p = <0.001. More proportion of infected women had maternal anaemia and gave preterm birth, and none of the newborn babies was HIV infected until the age of 96 weeks. It is thus HIV infected women in eastern Sudan were young and likely desire more children. PMID- 27184859 TI - One-pot hydrothermal synthesis of Nitrogen-doped graphene as high-performance anode materials for lithium ion batteries. AB - Nitrogen-doped (N-doped) graphene has been prepared by a simple one-step hydrothermal approach using hexamethylenetetramine (HMTA) as single carbon and nitrogen source. In this hydrothermal process, HMTA pyrolyzes at high temperature and the N-doped graphene subsequently self-assembles on the surface of MgO particles (formed by the Mg powder reacting with H2O) during which graphene synthesis and nitrogen doping are simultaneously achieved. The as-synthesized graphene with incorporation of nitrogen groups possesses unique structure including thin layer thickness, high surface area, mesopores and vacancies. These structural features and their synergistic effects could not only improve ions and electrons transportation with nanometer-scale diffusion distances but also promote the penetration of electrolyte. The N-doped graphene exhibits high reversible capacity, superior rate capability as well as long-term cycling stability, which demonstrate that the N-doped graphene with great potential to be an efficient electrode material. The experimental results provide a new hydrothermal route to synthesize N-doped graphene with potential application for advanced energy storage, as well as useful information to design new graphene materials. PMID- 27184860 TI - The incidence of congenital malformations and variations in Gottingen minipigs. AB - Knowledge of the incidence of spontaneous congenital abnormalities is critical for the accurate interpretation of findings in teratogenicity studies in any species. In this paper, results of the examination of 1739 neonatal Gottingen Minipigs are presented. Over the 2-year period under consideration, the incidence of external and visceral malformations was less than 0.2 and 0.1%, respectively. The most common external malformations were syndactyly, limb hyperflexion, domed head and scoliosis. The most common internal malformations were undescended testes, ventricular septal defect, diaphragmatic hernia and atrial septal defects. Pentadactyly and variation in the aortic arch's bifurcation (absent truncus bicaroticus) were the most common variations. These data will help support the use of the Gottingen Minipig as a non-rodent species in embryofetal development studies where concerns persist about the availability of background data. PMID- 27184861 TI - Mass spectrometry-based proteomics of oxidative stress: Identification of 4 hydroxy-2-nonenal (HNE) adducts of amino acids using lysozyme and bovine serum albumin as model proteins. AB - Modification of proteins by 4-hydroxy-2-nonenal (HNE), a reactive by-product of omega6 polyunsaturated fatty acid oxidation, on specific amino acid residues is considered a biomarker for oxidative stress, as occurs in many metabolic, hereditary, and age-related diseases. HNE modification of amino acids can occur either via Michael addition or by formation of Schiff-base adducts. These modifications typically occur on cysteine (Cys), histidine (His), and/or lysine (Lys) residues, resulting in an increase of 156 Da (Michael addition) or 138 Da (Schiff-base adducts), respectively, in the mass of the residue. Here, we employed biochemical and mass spectrometry (MS) approaches to determine the MS "signatures" of HNE-modified amino acids, using lysozyme and BSA as model proteins. Using direct infusion of unmodified and HNE-modified lysozyme into an electrospray quadrupole time-of-flight mass spectrometer, we were able to detect up to seven HNE modifications per molecule of lysozyme. Using nanoLC-MS/MS, we found that, in addition to N-terminal amino acids, Cys, His, and Lys residues, HNE modification of arginine (Arg), threonine (Thr), tryptophan (Trp), and histidine (His) residues can also occur. These sensitive and specific methods can be applied to the study of oxidative stress to evaluate HNE modification of proteins in complex mixtures from cells and tissues under diseased versus normal conditions. PMID- 27184862 TI - Identification of a novel HLA-A allele, HLA-A*01:195, in a UAE national. AB - A novel human leucocyte antigen (HLA)-A allele, HLA-A*01:195, was identified by sequence-based typing (SBT) in a UAE national subject. The novel allele is identical to its closest known allele, HLA-A*01:01:01:01, in exon 2, 3 and 4, except for a single nucleotide mutation of A to G at position 442 in exon 3 (codon 124 in the alpha2 domain of the alpha chain of the mature protein). This A to G mutation results in an amino acid change of isoleucine #124 to valine. PMID- 27184863 TI - HLA-DRB1 in Henoch-Schonlein purpura: A susceptibility study from North India. AB - Etiology of Henoch-Schonlein purpura (HSP) a small vessel vasculitis remains elusive. Susceptibility may be conferred by major histocompatibility complex. There are limited reports on the association of human leucocyte antigens (HLA) and HSP. The aim was to investigate the association of HLA-DRB1 (HLA class II antigen) with HSP. Forty three patients, <14years, who fulfilled the diagnostic criteria of HSP, laid by 'European League Against Rheumatism' were enrolled. Fifty four age-matched, healthy controls were included. PCR with 24 sequence specific primers for HLA-DRB1 allotypes was performed. Commercially available HLA DR tissue typing kit (Inno-train, Kronberg im Taunus, Hesse, Germany) was utilized. The mean age of patients and controls was 8.5+/-3.2 and 7.6+/-3.6years, respectively (p=0.18). Gastrointestinal and renal involvement was observed in 25 (58.1%) and 14 (32.6%) patients, respectively. A greater frequency of HLA-DRB1*11 was observed in patients (11.6%) as compared to controls (1.9%), however, the results were not significant following Bonferroni correction. No significantly protective HLA genotype was observed. None of the HLA-DRB1 antigen was noted to increase the susceptibility to gastrointestinal or renal involvement. In conclusion, in the first study from India, none of the HLA-DRB*1 genotypes were observed to increase the susceptibility of North Indian children to HSP. PMID- 27184864 TI - Thin Insulating Tunneling Contacts for Efficient and Water-Resistant Perovskite Solar Cells. AB - Tunneling contacts made of any insulating polymers, a champion technology in silicon solar cells, are shown to increase the stabilized efficiency of perovskite solar cells (PSCs) to 20.3%. The tunneling layers spatially separate photo-generated electrons and holes at the perovskite-cathode interface and reduce charge recombination. The tunneling layers made of hydrophobic polymers also significantly enhance the resistance of PSCs to water-caused damage. PMID- 27184869 TI - First heterometallic Ga(III)-Dy(III) single-molecule magnets: implication of Ga(III) in extracting Fe-Dy interaction. AB - The compounds of the system [M4M'2(MU3-OH)2(nbdea)4(C6H5CO2)8].MeCN, where M = Ga(III), M' = Dy(III) (), M = Fe(III), M' = Y(III) () are isostructural to the known [Fe4Dy2] compound (). Those of the system [M4M'4(MU3-OH)4(nbdea)4(m CH3C6H4CO2)12].nMeCN, where M = Ga(III), M' = Dy(III), n = 4 (), M = Fe(III), M' = Y(III), n = 1 () are isostructural to the [Fe4Dy4] compound (). This allows for comparisons between single ion effects of the paramagnetic ions. The structures were determined using single crystal analysis. Magnetic susceptibility measurements reveal that the Ga(III)-Dy(III) compounds and are SMMs. The energy barrier for is close to that for the known isostructural Fe4Dy2 compound (), but with a significantly increased relaxation time. PMID- 27184870 TI - The Immunosuppressive Effect of CTLA4 Immunoglobulin Is Dependent on Regulatory T Cells at Low But Not High Doses. AB - B7.1/2-targeted costimulation blockade (CTLA4 immunoglobulin [CTLA4-Ig]) is available for immunosuppression after kidney transplantation, but its potentially detrimental impact on regulatory T cells (Tregs) is of concern. We investigated the effects of CTLA4-Ig monotherapy in a fully mismatched heart transplant model (BALB/c onto C57BL/6). CTLA4-Ig was injected chronically (on days 0, 4, 14, and 28 and every 4 weeks thereafter) in dosing regimens paralleling clinical use, shown per mouse: low dose (LD), 0.25 mg (~10 mg/kg body weight); high dose (HD), 1.25 mg (~50 mg/kg body weight); and very high dose (VHD), 6.25 mg (~250 mg/kg body weight). Chronic CTLA4-Ig therapy showed dose-dependent efficacy, with the LD regimen prolonging graft survival and with the HD and VHD regimens leading to >95% long-term graft survival and preserved histology. CTLA4-Ig's effect was immunosuppressive rather than tolerogenic because treatment cessation after ~3 mo led to rejection. FoxP3-positive Tregs were reduced in naive mice to a similar degree, independent of the CTLA4-Ig dose, but recovered to normal values in heart recipients under chronic CTLA4-Ig therapy. Treg depletion (anti-CD25) resulted in an impaired outcome under LD therapy but had no detectable effect under HD therapy. Consequently, the immunosuppressive effect of partially effective LD CTLA4-Ig therapy is impaired when Tregs are removed, whereas CTLA4-Ig monotherapy at higher doses effectively maintains graft survival independent of Tregs. PMID- 27184871 TI - Supporting medics' and corpsmen's move into professional nursing. PMID- 27184873 TI - From MIC creep to MIC decline: Staphylococcus aureus antibiotic susceptibility evolution over the last 4 years. PMID- 27184872 TI - Detection of Circulating Tumor Cells by Fluorescent Immunohistochemistry in Patients with Esophageal Squamous Cell Carcinoma: Potential Clinical Applications. AB - BACKGROUND Circulating tumor cells (CTCs) are tumor cells that leave the primary tumor site and enter the bloodstream, where they can spread to other organs; they are very important in the diagnosis, treatment, and prognosis of malignant tumors. However, few studies have investigated CTCs in esophageal squamous cell carcinoma (ESCC). The aim of this study was to investigate the CTCs in blood of ESCC patients and its potential relevance to clinicopathological features and prognosis. MATERIAL AND METHODS CTCs were acquired by a negative enrichment method that used magnetic activated cell sorting (MACSTM). Fluorescent immunohistochemistry (IHC) was used to identify the CTCs. Then, the positive CTC patients with ESCC were analyzed, after which the relationship between CTCs and clinicopathologic features was evaluated. RESULTS In the present study, 62 out of 140 (44.3%) patients with ESCC were positive for CTCs. The positive rate of CTCs was significantly related with stage of ESCC patients (P=0.013). However, there was no relationship between CTC status and age, sex, smoking tumor history, tumor location, differentiation of tumor, lymphatic invasion, or lymph venous invasion (P>0.05). Kaplan-Meier analysis showed that patients positive for CTCs had significantly shorter survival time than patients negative for CTCs. Multivariate analysis demonstrated that stage and CTC status were significant prognostic factors for patients with ESCC. CONCLUSIONS CTCs positivity is an independent prognostic biomarker that indicates a worse prognosis for patients with ESCC. PMID- 27184874 TI - Suddenly everyone is a microbiota specialist. PMID- 27184875 TI - Equal sensitivity of the new generation QuantiFERON-TB Gold plus in direct comparison with the previous test version QuantiFERON-TB Gold IT. AB - QuantiFERON-TB Gold IT analyses interferon-gamma release from CD4(+) T cells after stimulation with specific tuberculosis (TB) antigens. Its sensitivity is approximately 80% for active TB. A new test generation (QFTGplus) also analyses the response of CD8(+) T cells. We investigated both test generations in a direct head-to-head comparison in a German pulmonary hospital. Sensitivity rates for active TB were identical, no matter whether diagnosis was bacteriologically confirmed or not. PMID- 27184876 TI - Observational studies examining patient management in infectious diseases. PMID- 27184877 TI - Corticosteroid dosage for acute bacterial meningitis in children. PMID- 27184878 TI - Psychiatric and Behavioural Disorders in Children with Epilepsy (ILAE Task Force Report): Adverse cognitive and behavioural effects of antiepileptic drugs in children. AB - The literature was evaluated for cognitive and more general behavioural effects. We distinguished the older antiepileptic drugs (AEDs), from the newer and newest AEDs. The striking finding was the lack of information on children. From the available evidence it would appear that there may be negative cognitive effects with phenobarbital, phenytoin, topiramate and zonisamide, and adverse behavioural effects with phenobarbital, valproate, gabapentin, topiramate, levetiracetam and zonisamide. There is inconclusive data on ethosuximide, clobazam, vigabatrin, felbamate, pregabalin, stiripentol, rufinamide, lacosamide and retigabine. The following drugs appear to be neutral with regard to cognitive effects: valproate, carbamazepine, gabapentin and oxcarbazepine. Carbamazepine appears to be neutral with regard to behavioural effects. Positive cognitive effects have been reported with lamotrigine and levetiracetam. Positive behavioural effects have been reported with lamotrigine. Recommendations are provided. PMID- 27184879 TI - Commentary on Some Recent Theses Relevant to Combating Aging: June 2016. PMID- 27184880 TI - Serum and Urinary Interferon-Gamma-Inducible Protein 10 in Lupus Nephritis. AB - BACKGROUND: Lupus nephritis is a serious manifestation of systemic lupus erythematosus (SLE). The objective of this study was to identify the sensitivity, specificity, and cut-off values of IP-10 in the serum and urine of patients with lupus nephritis compared to renal biopsy, albumin/creatinine ratio, and serum anti-dsDNA. METHODS: Thirty female SLE patients were included. SLEDAI was calculated and blood and urine samples were collected. Patients were divided into 10 SLE patients with renal involvement (six active and four inactive), 10 active SLE, and 10 inactive SLE patients. Ten age-matched healthy (control) were included. Serum and urinary levels of IP-10 were measured by ELISA. Anti-dsDNA, urine albumin/creatinine ratio were performed. RESULTS: Serum and urinary IP-10 in active SLE patients had significantly increased levels as compared to inactive SLE patients (P = 0.015, P = 0.033, respectively). However, there was no difference in serum and urinary levels between active renal and active non-renal patients. Albumin/creatinine ratio is a better marker in differentiating between lupus nephritis and SLE with no renal involvement. Any of serum and urinary IP 10, albumin/creatinine ratio, and anti-dsDNA did not correlate with the class of lupus nephritis in renal biopsy. CONCLUSION: Urinary and serum IP-10 are useful markers of lupus activity, but not indicative of renal activity. Albumin/creatinine ratio is superior in identifying lupus nephritis and renal activity. PMID- 27184881 TI - Exercise increases mitochondrial glutamate oxidation in the mouse cerebral cortex. AB - The present study investigated the impact of acute exercise on stimulating mitochondrial respiratory function in mouse cerebral cortex. Where pyruvate stimulated respiration was not affected by acute exercise, glutamate respiration was enhanced following the exercise bout. Additional assessment revealed that this affect was dependent on the presence of malate and did not occur when substituting glutamine for glutamate. As such, our results suggest that glutamate oxidation is enhanced with acute exercise through activation of the malate aspartate shuttle. PMID- 27184883 TI - Correlation between quadriceps to hamstring ratio and functional outcomes in patellofemoral pain. AB - BACKGROUND: The aim of this study was to investigate the correlation between quadriceps to hamstring (Q:H) ratio and the functional outcomes in Patellofemoral Pain (PFP) patients. METHODS: The study included forty-four women diagnosed with unilateral PFP. Eccentric and concentric quadriceps and hamstring strength were recorded. Conventional Q:H ratio was calculated as the concentric quadriceps to concentric hamstring peak torque (Ratio 1). Functional ratios were calculated as the eccentric quadriceps to concentric hamstring peak torque (Ratio 2) and as the concentric quadriceps to eccentric hamstring torque (Ratio 3). Functional levels of the patients were determined by using Kujala scores, hop test and step test. Pain levels during activities were recorded. The relationship among Ratio 1, Ratio 2 and Ratio 3 with functional outcomes and pain levels were evaluated using Spearman's correlation coefficient test. RESULTS: Eccentric and concentric quadriceps and hamstring strength were lower on involved side than uninvolved side. Ratio 2 correlated stronger with Kujala score (r=0.69) than Ratio 1 (r=0.49) and Ratio 3 (r=0.30). Step test (r=0.35) and hop test (r=0.38) only correlated with Ratio 2. Pain levels correlated more with Ratio 2 (r values ranged between 0.38 and 0.48). CONCLUSION: Eccentric quadriceps to concentric hamstring ratio was observed more related to the functional outcomes and painful activities in patients with PFP. LEVEL OF EVIDENCE III: Cross-sectional study. PMID- 27184882 TI - TT-TG vs. modified lateral patellar edge for determination of tibial tubercle transfer distance in Fulkerson osteotomy procedures. AB - BACKGROUND: Tibial tubercle-trochlear groove (TT-TG) distance is currently used at our institution to determine tibial tubercle medialization required in Fulkerson osteotomies. If the correlation between a modified lateral patellar edge (LPE) and the transfer distance was found to be stronger than its correlation with TT-TG, it would suggest that the best measurement to use is actually modified LPE. METHODS: The electronic medical records of 32 patients who underwent Fulkerson osteotomy procedures with femoral nerve stimulation were reviewed and measured. For each patient, modified LPE was measured on quadriceps active hyperextension MRI, and TT-TG was measured on passive extension MRI. Correlation between both TT-TG and LPE and tibial tubercle transfer distance was then determined and analysed. RESULTS: The correlation between TT-TG and actual intra-operative tibial tubercle transfer distance in Fulkerson osteotomy procedures with intra-operative femoral nerve stimulation was found to be weak at 0.436 (p<0.05). The correlation between modified LPE and actual intra-operative tibial tubercle transfer distance was found to be strong at 0.697 (p<0.001). CONCLUSIONS: The correlation between modified LPE and actual intra-operative tibial tubercle transfer distance was stronger than the correlation between TT-TG and tibial tubercle transfer distance. This suggests that the modified LPE may actually be a better preoperative determinant than the currently-utilized TT-TG of the transfer distance required during Fulkerson osteotomy procedures. LEVEL OF EVIDENCE: Level II, diagnostic study. PMID- 27184884 TI - The rumen and beyond: Nutritional physiology of the modern dairy cow. PMID- 27184885 TI - Corrigendum to "Australian milk fat-Seasonal and regional variation of melting properties" (J. Dairy Sci. 99:2571-2587). PMID- 27184886 TI - Comparative lipidomics and proteomics analysis of platelet lipid rafts using different detergents. AB - Lipid rafts play a pivotal role in physiological functions of platelets. Their isolation using nonionic mild detergents is considered as the gold standard method, but there is no consensual detergent for lipid raft studies. We aimed to investigate which detergent is the most suitable for lipid raft isolation from platelet membrane, based on lipidomics and proteomics analysis. Platelets were obtained from healthy donors. Twelve sucrose fractions were extracted by three different detergents, namely Brij 35, Lubrol WX, and Triton X100, at 0.05% and 1%. After lipidomics analysis and determination of fractions enriched in cholesterol (Ch) and sphingomyelin (SM), proteomics analysis was performed. Lipid rafts were mainly observed in 1-4 fractions, and non-rafts were distributed on 5 12 fractions. Considering the concentration of Ch and SM, Lubrol WX 1% and Triton X100 1% were more suitable detergents as they were able to isolate lipid raft fractions that were more enriched than non-raft fractions. By proteomics analysis, overall, 822 proteins were identified in platelet membrane. Lipid raft fractions isolated with Lubrol WX 0.05% and Triton X100 1% contained mainly plasma membrane proteins. However, only Lubrol WX 0.05 and 1% and Triton X100 1% were able to extract non-denaturing proteins with more than 10 transmembrane domains. Our results suggest that Triton X100 1% is the most suitable detergent for global lipid and protein studies on platelet plasma membrane. However, the detergent should be adapted if investigation of an association between specific proteins and lipid rafts is planned. PMID- 27184887 TI - MicroRNA-150 Inhibits the Activation of Cardiac Fibroblasts by Regulating c-Myb. AB - BACKGROUND/AIMS: Cardiac fibrosis is the primary cause of deteriorated cardiac function in various cardiovascular diseases. Numerous studies have demonstrated that microRNAs (miRNAs) are critical regulators of myocardial fibrosis. Specifically, many studies have reported that miR-150 is downregulated in cardiovascular diseases, such as acute myocardial infarction (AMI), myocardial hypertrophy and myocardial fibrosis. However, the exact role of miR-150 in these pathological processes remains unknown. METHODS: We used the transverse aortic constriction (TAC) mouse model to study the role of miR-150 in cardiac fibrosis induced by pressure overload. After the TAC operation, qRT-PCR was used to measure the expression profiles of miR-150 in left ventricle tissues and populations of primary heart cell types. Then, we used both miR-150 knockout mice and wild type (WT) mice in the TAC model. Changes in cardiac function and pathology were measured using transthoracic echocardiography and pathological analysis, respectively. Furthermore, we predicted the target of miR-150 in cardiac fibroblasts (CFs) and completed in vitro CF transfection experiments using miR-150 analogs and siRNA corresponding to the predicted target. RESULTS: We observed decreased expression levels of miR-150 in hearts suffering pressure overload, and these levels decreased more sharply in CFs than in cardiomyocytes. In addition, the degrees of cardiac function deterioration and cardiac fibrosis in miR-150-/- mice were more severe than were those in WT mice. By transfecting CFs with an miR-150 analog in vitro, we observed that miR-150 inhibited cardiac fibroblast activation. We predicted that the transcription factor c-Myb was the target of miR-150 in CFs. Transfecting CFs with c-Myb siRNA eliminated the effects of an miR-150 inhibitor, which promoted CF activation. CONCLUSION: These findings reveal that miR-150 acts as a pivotal regulator of pressure overload induced cardiac fibrosis by regulating c-Myb. PMID- 27184890 TI - Response to "Variable directionality of gene expression changes across generations does not constitute negative evidence of epigenetic inheritance" Sharma, A. Environmental Epigenetics, 2015, 1-5. AB - Abhay Sharma brings two arguments in favor of transgenerational epigenetic inheritance (TGEI) in mammals when criticizing our work. He uses probability calculations and finds that the probability of obtaining the number of common changes in the in utero-exposed prospermatogonia and the same cells in the next generation is significant in our study. He also compares our results to other published datasets and concludes that the probability for the observed overlap between independent studies is significant. We disagree with both arguments of Sharma and show here that his meta-analysis and statistical calculations are not correct. PMID- 27184889 TI - A Quantitative Theoretical Framework For Protein-Induced Fluorescence Enhancement Forster-Type Resonance Energy Transfer (PIFE-FRET). AB - Single-molecule, protein-induced fluorescence enhancement (PIFE) serves as a molecular ruler at molecular distances inaccessible to other spectroscopic rulers such as Forster-type resonance energy transfer (FRET) or photoinduced electron transfer. In order to provide two simultaneous measurements of two distances on different molecular length scales for the analysis of macromolecular complexes, we and others recently combined measurements of PIFE and FRET (PIFE-FRET) on the single molecule level. PIFE relies on steric hindrance of the fluorophore Cy3, which is covalently attached to a biomolecule of interest, to rotate out of an excited-state trans isomer to the cis isomer through a 90 degrees intermediate. In this work, we provide a theoretical framework that accounts for relevant photophysical and kinetic parameters of PIFE-FRET, show how this framework allows the extraction of the fold-decrease in isomerization mobility from experimental data, and show how these results provide information on changes in the accessible volume of Cy3. The utility of this model is then demonstrated for experimental results on PIFE-FRET measurement of different protein-DNA interactions. The proposed model and extracted parameters could serve as a benchmark to allow quantitative comparison of PIFE effects in different biological systems. PMID- 27184888 TI - Recovery-focused care planning and coordination in England and Wales: a cross national mixed methods comparative case study. AB - BACKGROUND: In the UK, concerns about safety and fragmented community mental health care led to the development of the care programme approach in England and care and treatment planning in Wales. These systems require service users to have a care coordinator, written care plan and regular reviews of their care. Processes are required to be collaborative, recovery-focused and personalised but have rarely been researched. We aimed to obtain the views and experiences of stakeholders involved in community mental health care and identify factors that facilitate or act as barriers to personalised, collaborative, recovery-focused care. METHODS: We conducted a cross-national comparative study employing a concurrent transformative mixed-methods approach with embedded case studies across six service provider sites in England and Wales. The study included a survey of views on recovery, empowerment and therapeutic relationships in service users (n = 448) and recovery in care coordinators (n = 201); embedded case studies involving interviews with service providers, service users and carers (n = 117) and a review of care plans (n = 33). Quantitative and qualitative data were analysed within and across sites using inferential statistics, correlations and framework method. RESULTS: Significant differences were found across sites for scores on therapeutic relationships. Variation within sites and participant groups was reported in experiences of care planning and understandings of recovery and personalisation. Care plans were described as administratively burdensome and were rarely consulted. Carers reported varying levels of involvement. Risk assessments were central to clinical concerns but were rarely discussed with service users. Service users valued therapeutic relationships with care coordinators and others, and saw these as central to recovery. CONCLUSIONS: Administrative elements of care coordination reduce opportunities for recovery focused and personalised work. There were few common understandings of recovery which may limit shared goals. Conversations on risk appeared to be neglected and assessments kept from service users. A reluctance to engage in dialogue about risk management may work against opportunities for positive risk-taking as part of recovery-focused work. Research to investigate innovative approaches to maximise staff contact time with service users and carers, shared decision-making in risk assessments, and training designed to enable personalised, recovery focused care coordination is indicated. PMID- 27184892 TI - Clinical and economic impact of a specific BCG vaccination program implemented in Prato, central Italy, involving foreign newborns on hospitalizations. AB - In Tuscany (Central Italy), the average annual notification rate of tuberculosis (TB) in the years 2007-2012 was 7.5-9.8 per 100,000 people, with the Local Health Unit of Prato (LHU4) showing the highest rate compared to the other regional area. Therefore, in order to reduce the burden of TB, foreign newborns in the LHU4 are being given the Bacillus Calmette-Guerin (BCG) vaccine since 2000. The aim of this study is to assess the impact of BCG vaccination in Prato, in terms of TB-related hospitalizations and costs. The regional archive containing all TB related discharges and costs in the period 2007-2014 was consulted. Data regarding foreigners living in the LHU4 who have been vaccinated since 2000 were compared with those living in the other Tuscan LHUs and never vaccinated. These populations were then disaggregated by a threshold age of 15 y. After calculating the standardized hospitalization rates, the expected number of hospitalizations for TB among unvaccinated adults (in both populations) was found to be similar in the LHU4 and the other LHUs (165 vs. 156). However, expected number of hospitalizations among children in the other Tuscan LHUs (67) was double that of the LHU4 (34). If the same vaccine had been administrated everywhere, each year 29 hospitalizations could have been avoided and EUR 343,525 saved. Overall, BCG vaccinations cost EUR 14,879 in the LHU4, but 69 hospitalizations were avoided and EUR 107,435 saved. The introduction of the BCG immunization program in the LHU4 of Prato has led to significant reductions in the clinical and economic impact of TB. PMID- 27184891 TI - The relationship between Lp(a) and CVD outcomes: a systematic review. AB - Robust associations between lipoprotein(a) [Lp(a)] and CVD outcomes among general populations have been published in previous studies. However, associations in high risk primary prevention and secondary prevention populations are less well defined. In order to investigate this further, a systematic review was performed including prospective studies, which assessed the relationship between Lp(a) and CVD outcomes using multivariable analyses. Additional information was gathered on Lp(a) assays, multivariable modelling and population characteristics. Literature searches from inception up to December 2015 retrieved 2850 records. From these 60 studies were included. Across 39 primary prevention studies in the general population (hazard ratios ranged from 1.16 to 2.97) and seven high risk primary prevention studies (hazard ratios ranged from 1.01 to 3.7), there was evidence of a statistically significant relationship between increased Lp(a) and an increased risk of future CVD. Results in 14 studies of secondary prevention populations were also suggestive of a modest statistically significant relationship (hazard ratios ranged from 0.75 to 3.7).Therefore current evidence would suggest that increased Lp(a) levels are associated with modest increases in the risk of future CVD events in both general and higher risk populations. However, further studies are required to confirm these findings. PMID- 27184893 TI - Effects of fetal genotype and sex on developmental response to maternal malnutrition. AB - The present study aimed to determine whether developmental patterns, adiposity level and fatty-acid composition of fetuses exposed to maternal malnutrition are driven by their sex or their genotype, or both, as these may modulate the adaptive response to the intrauterine environment independently of the maternal genotype. We used a single maternal genotype (purebred Iberian (IB) sows), which was inseminated with heterospermic semen (obtained by mixing semen from Iberian and Large White (LW) boars), to obtain four different subsets of fetuses (male and female, purebred (IB*IB) and crossbred (IB*LW)) in Iberian purebred sows. Analysis of fetal phenotypes indicated a better adaptive response of the female offspring, which was modulated by their genotype. When faced with prenatal undernutrition, females prioritised the growth of vital organs (brain, liver, lungs, kidneys and intestine) at the expense of bone and muscle. Moreover, the analysis of fat composition showed a higher availability of essential fatty acids in the female sex than in their male counterparts and also in the Iberian genotype than in crossbred fetuses. These results are of high translational value for understanding ethnic differences in prenatal programming of postnatal health and disease status, and show evidence that prenatal development and metabolic traits are primarily determined by fetal sex and strongly modulated by fetal genotype. PMID- 27184894 TI - Living with moderate to severe renal failure from the perspective of patients. AB - BACKGROUND: Within healthcare, almost no attention is given to patients with moderate-to- severe chronic kidney disease, having a with GFR between 20 and 45 while the presumption exists that these patients already experience several problems in their lives during the course of their illness. METHODS: A team of academic researchers and a renal patient participated in a qualitative study. Individual interviews (n = 31) and focus groups (10 participants in total) with patients having moderate-to-severe chronic kidney disease were conducted to gain insight into their everyday problems. RESULTS: Participants mentioned several experiences that can be divided into physical, social, societal and psychological aspects as well as aspects related to healthcare. The most important findings, following under each of these categories are: 1) the experience of fatigue (physical aspects) 2) the search for acknowledgment of complaints/not enough attention given to complaints leading to overcompensation and secrecy (societal aspects) 3) work problems (societal aspects) and 4) the wish to control the disease but not receiving enough support for this (healthcare). Patients feel in general that healthcare professionals do not take them seriously in their complaints and problems. CONCLUSIONS: This study offers important new insights into an expanding group of patients having moderate-to-severe chronic kidney disease. Healthcare professionals should acknowledge their problems instead of ignoring or rejecting them and they should support patients in finding a way to deal with them. The assumptions of Personalised Care Planning could be used to support patients. PMID- 27184896 TI - Brainjacking: Implant Security Issues in Invasive Neuromodulation. AB - The security of medical devices is critical to good patient care, especially when the devices are implanted. In light of recent developments in information security, there is reason to be concerned that medical implants are vulnerable to attack. The ability of attackers to exert malicious control over brain implants ("brainjacking") has unique challenges that we address in this review, with particular focus on deep brain stimulation implants. To illustrate the potential severity of this risk, we identify several mechanisms through which attackers could manipulate patients if unauthorized access to an implant can be achieved. These include blind attacks in which the attacker requires no patient-specific knowledge and targeted attacks that require patient-specific information. Blind attacks include cessation of stimulation, draining implant batteries, inducing tissue damage, and information theft. Targeted attacks include impairment of motor function, alteration of impulse control, modification of emotions or affect, induction of pain, and modulation of the reward system. We also discuss the limitations inherent in designing implants and the trade-offs that must be made to balance device security with battery life and practicality. We conclude that researchers, clinicians, manufacturers, and regulatory bodies should cooperate to minimize the risk posed by brainjacking. PMID- 27184899 TI - Intraoperative Motor-Evoked Potential Monitoring as a Predictive Tool for Recovery From Spontaneous Intracerebral Hemorrhage. PMID- 27184897 TI - Fiber Tracts of the Medial and Inferior Surfaces of the Cerebrum. AB - OBJECTIVE: Fiber dissection studies of the cerebrum have focused on the lateral surface. No comparable detailed studies have been done on the medial and inferior surfaces. The object of this study was to examine the fiber tracts, cortical, and subcortical structures of the medial and inferior aspects of the brain important in planning operative approaches along the interhemispheric fissure, parafalcine area, and basal surfaces of the cerebrum. METHODS: Twenty formalin-fixed human hemispheres (10 brains) were examined by fiber dissection technique under *6-*40 magnifications. RESULTS: The superior longitudinal fasciculus I, cingulum, inferior longitudinal fasciculus, uncinate fasciculus, optic radiations, tapetum, and callosal fibers were dissected step by step from medial to lateral, exposing the nucleus accumbens, subthalamic nucleus, red nucleus, and central midline structures (fornix, stria medullaris, and stria terminalis). Finally, the central core structures were dissected from medial to lateral. CONCLUSIONS: Understanding the fiber network underlying the medial and inferior aspects of the brain is important in surgical planning for approaches along the interhemispheric fissure, parafalcine area, and basal surfaces of the cerebrum. PMID- 27184898 TI - Preoperative and Postoperative Factors and Laboratory Values Predicting Outcome in Patients Undergoing Lumbar Fusion Surgery. AB - OBJECTIVE: To determine whether complications in lumbar fusion surgery could be estimated from patient factors and perioperative laboratory values. In addition, risk scores for detection of patients prone to complications were defined. METHODS: We retrospectively collected data of patients undergoing lumbar fusion surgery between 2013 and 2015. The patients were divided into group A (no complications) and group B (systemic and infectious complications within 30 days postoperatively). Patient-related factors and levels of perioperative laboratory values were compared between the groups and analyzed for possible impact on complications and length of stay (LOS) in the hospital. RESULTS: Data of 132 consecutive patients (74 women [56.1%]; median age, 68.5 years) were analyzed. Postoperative complications occurred in 29.5%. Higher postoperative creatine kinase (CK) and C-reactive protein and lower postoperative hemoglobin and thrombocyte values, as well as higher differences between preoperative and postoperative CK, C-reactive protein, and hemoglobin values were associated with postoperative complications. Among others, the combinations of advanced age and elevated body mass index (P = 0.0062, odds ratio: 3.018), or advanced age, elevated body mass index, and postoperative CK >166 U/L (P = 0.0016, odds ratio: 3.637) revealed patients with a threefold risk for complications. The combination of advanced age, American Society of Anesthesiologists score >2, and preoperative hemoglobin <12.9 g/dL was associated with a LOS of 20.3 versus 11 days (P = 0.01). CONCLUSIONS: Patients with postoperative complications and extended LOS seem to show significant differences in various perioperative laboratory values and patient factors. Perioperative risk assessments using cut-off values and risk scores may help identify patients prone to complications and extended resource use. PMID- 27184900 TI - Globus Pallidus Internus Deep Brain Stimulation for Traumatic Hemidystonia Following Penetrating Head Injury. AB - BACKGROUND: Deep brain stimulation (DBS) has been a major advance in the treatment of dystonias. Outcomes are, however, less predictable for secondary dystonias, predominantly due to progression of disease or specific brain lesions. There are few cases reported of globus pallidus internus (GPi)-DBS for posttraumatic dystonia. We describe the successful use of unilateral GPi-DBS in a patient with hemidystonia following penetrating head injury. To our knowledge, this is the first description of the use of DBS following penetrating head injury. CASE DESCRIPTION: We present the case of a 47-year-old man with phasic hemidystonia. At the age of 3 years he suffered a penetrating head injury from a welding needle. The patient developed dystonic and phasic right-sided movements. Preoperative Burke-Fahn-Marsden score was 26. Magnetic resonance imaging showed a linear encephalomalacic track extending from the cortex in the left parieto occipital region, traversing just superolateral to the left trigone into the left thalamus and ending in the region of left cerebral peduncle and subthalamic nucleus. There was no left GPi lesion. A left GPi-DBS electrode was inserted. At 6 months' follow-up, the patient's arm was more relaxed and his spasms lessened in their severity and frequency. Although the Burke-Fahn-Marsden score of 21 had improved modestly by 20%, pain and comfort levels had significantly improved with 50% improvement in visual analog scale score, translating in better quality of life. There were no complications. The clinical benefit persists at 5 years post surgery. CONCLUSION: Selected patients with posttraumatic hemidystonia, including following penetrating head injury, represent one group of secondary dystonias that might benefit from DBS surgery. PMID- 27184901 TI - Good Surgical Outcomes of Hemifacial Spasm Patients with Obvious Facial Nerve Indentation and Color Change. AB - OBJECTIVES: Hemifacial spasm results from vascular compression of the facial nerve. It remains controversial whether severe compression and subsequent nerve indentation predict a good or a poor surgical outcome. Here, to illustrate the relationship between the degree of neurovascular compression and surgical outcome, we conducted a retrospective case-cohort study focused on patients whose facial nerve was seriously compressed. METHODS: This study included 2 groups. The nerve-indentation group included 48 patients with hemifacial spasm whose facial nerves had obvious indentation and color change at the site of neurovascular conflict. The control group included 48 randomly selected patients with hemifacial spasm without facial nerve indentation or color change who were surgically treated by the same team during the same period. The surgical findings, intraoperative lateral spread response results, and clinical outcomes were compared. RESULTS: Single-vessel compression was found more frequently in the nerve-indentation group (87.5%) than in the control group (60.4%, P < 0.05). The lateral spread response (LSR) resolution rate of the nerve-indentation group was 91.7%, and that of the control group was 87.5% (P > 0.05). The rates at which the microvascular decompression procedure was successful were equal in the nerve indentation and the control groups (93.8% vs. 91.7%, P > 0.05). CONCLUSIONS: Severe vascular compression and subsequent nerve indentation were correlated with a greater possibility of single compression and a lower incidence of multiple neurovascular conflicts in patients with hemifacial spasm, making the microvascular decompression procedure more accurate and easier. Therefore nerve indentation might predict good surgical outcomes. PMID- 27184902 TI - Transitional care in skilled nursing facilities: a multiple case study. AB - BACKGROUND: Among hospitalized older adults who transfer to skilled nursing facilities (SNF) for short stays and subsequently transfer to home, twenty two percent require additional emergency department or hospital care within 30 days. Transitional care services, that provide continuity and coordination of care as older adults transition between settings of care, decrease complications during transitions in care, however, they have not been examined in SNFs. Thus, this study described how existing staff in SNFs delivered transitional care to identify opportunities for improvement. METHODS: In this prospective, multiple case study, a case was defined as an individual SNF. Using a sampling plan to assure maximum variation among SNFs, three SNFs were purposefully selected and 54 staff, patients and family caregivers participated in data collection activities, which included observations of care (N = 235), interviews (N = 66) and review of documents (N = 35). Thematic analysis was used to describe similarities and differences in transitional care provided in the SNFs as well as organizational structures and the quality of care-team interactions that supported staff who delivered transitional care services. RESULTS: Staff in Case 1 completed most key transitional care services. Staff in Cases 2 and 3, however, had incomplete and/or absent services. Staff in Case 1, but not in Cases 2 and 3, reported a clear understanding of the need for transitional care, used formal transitional care team meetings and tracking tools to plan care, and engaged in robust team interactions. CONCLUSIONS: Organizational structures in SNFs that support staff and interactions among patients, families and staff appeared to promote the ability of staff in SNFs to deliver evidence-based transitional care services. Findings suggest practical approaches to develop new care routines, tools, and staff training materials to enhance the ability of existing SNF staff to effectively deliver transitional care. PMID- 27184903 TI - Limitations of Rb-82 weight-adjusted dosing accuracy at low doses. AB - INTRODUCTION: Weight-adjusted dosing is important to maintain accurate quantification for dynamic cardiac three-dimensional positron emission tomography (PET). However, the manufacturer of the only Food and Drug Administration approved rubidium-82 (Rb-82) generator (CardioGen-82, Bracco Diagnostics, Inc.) recommends recalibration after each change in dose which is inefficient in a busy clinical PET lab. The objective of this study was to evaluate the accuracy of Rb 82 dosing without this recalibration. METHODS: After daily calibration to either 30 mCi (1110 MBq) or 12 mCi (444 MBq), Rb-82 doses between 6 and 45 mCi (222-1665 MBq) were eluted and measured on an external dose calibrator. This was repeated for four generators at weeks 1, 2, or 4 of the generator cycle. The measurements were compared with values reported by the infusion system. RESULTS: For requested doses less than 30 mCi, the measured dose was consistently lower than the requested dose, ranging from -3.2 mCi at 25 mCi to -5.5 mCi at 10 mCi. The error exceeded 10% for doses less than or equal to 26 mCi for the 30 mCi calibration. Residual activity in the infusion system dead volume accounted for the discrepancy between requested and delivered doses for calibration to 30 mCi but not 12 mCi. CONCLUSIONS: The CardioGen-82 infusion system is capable of accurate weight-adjusted doses without recalibration for Rb-82 doses as low as 26 mCi when calibrated to 30 mCi. For doses less than 26 mCi, the generator-reported residual activity within the infusion system can be used to correct the delivered dose. PMID- 27184906 TI - From Insulation Breaks to Complete Lead Fracture: A Case Report. PMID- 27184904 TI - Exploring mechanisms of Panax notoginseng saponins in treating coronary heart disease by integrating gene interaction network and functional enrichment analysis. AB - OBJECTIVE: To investigate the mechanisms of Panax notoginseng saponins (PNS) in treating coronary heart disease (CHD) by integrating gene interaction network and functional enrichment analysis. METHODS: Text mining was used to get CHD and PNS associated genes. Gene-gene interaction networks of CHD and PNS were built by the GeneMANIA Cytoscape plugin. Advanced Network Merge Cytoscape plugin was used to analyze the two networks. Their functions were analyzed by gene functional enrichment analysis via DAVID Bioinformatics. Joint subnetwork of CHD network and PNS network was identifified by network analysis. RESULTS: The 11 genes of the joint subnetwork were the direct targets of PNS in CHD network and enriched in cytokine-cytokine receptor interaction pathway. PNS could affect other 85 genes by the gene-gene interaction of joint subnetwork and these genes were enriched in other 7 pathways. The direct mechanisms of PNS in treating CHD by targeting cytokines to relieve the inflflammation and the indirect mechanisms of PNS in treating CHD by affecting other 7 pathways through the interaction of joint subnetwork of PNS and CHD network. The genes in the 7 pathways could be potential targets for the immunologic adjuvant, anticoagulant, hypolipidemic, anti-platelet and anti-hypertrophic activities of PNS. CONCLUSIONS: The key mechanisms of PNS in treating CHD could be anticoagulant and hypolipidemic which are indicated by analyzing biological functions of hubs in the merged network. PMID- 27184905 TI - Metabolomic profiling reveals distinct patterns of tricarboxylic acid disorders in blood stasis syndrome associated with coronary heart disease. AB - OBJECTIVE: To investigate the underlying metabolomic profifiling of coronary heart disease (CHD) with blood stasis syndrome (BSS). METHODS: CHD model was induced by a nameroid constrictor in Chinese miniature swine. Fifteen miniature swine were randomly divided into a model group (n=9) and a control group (n=6), respectively according to arandom number table. After 4 weeks, plasma hemorheology was detected by automatic hemorheological analyzer, indices including hematocrit, plasma viscosity, blood viscosity, rigidity index and erythrocyte sedimentation rate; cardiac function was assessed by echocardiograph to detect left ventricular end-systolic diameter (LVED), left ventricular end diastolic diameter (LVEDd), ejection fraction (EF), fractional shortening (FS) and other indicators. Gas chromatography coupled with mass spectrometry (GC-MS) and bioinformatics were applied to analyze spectra of CHD plasma with BSS. RESULTS: The results of hemorheology analysis showed signifificant changes in viscosity, with low shear whole blood viscosity being lower and plasma viscosity higher in the model group compared with the control group. Moreover, whole blood reduction viscosity at high shear rate and whole blood reduction viscosity at low shear rate increased signifificantly (P <0.05). The echocardiograph results demonstrated that cardiac EF and FS showed signifificant difference (P <0.05), with EF values being decreased to 50% or less. The GC-MS data showed that principal component analysis can clearly separate the animals with BSS from those in the control group. The enriched Kyoto Encyclopedia of Genes and Genomes biological pathways results suggested that the patterns involved were associated with dysfunction of energy metabolism including glucose and lipid disorders, especially in glycolysis/gluconeogenesis, galactose metabolism and adenosine triphosphate-binding cassette transporters. CONCLUSIONS: Glucose metabolism and lipid metabolism disorders were the major contributors to the syndrome classifification of CHD with BSS. PMID- 27184907 TI - From local to global: a qualitative review of the multi-leveled impact of a multi country health research capacity development partnership on maternal health in Sudan. AB - BACKGROUND: There is a substantial body of literature on the principles of good partnerships and the rationale for such partnerships in research capacity strengthening. This paper illustrates the long term effects of a multi-country (8 countries) global partnership for health systems research capacity development (Connecting health Research in Africa and Ireland Consortium - ChRAIC) in relation to its contribution to capacity strengthening, public advocacy and policy influence at different levels and its practical achievements in Sudan in addressing access to maternal health services. METHODS: The authors (all members of the global partnership) reflect on the project in one of its' partner countries, Sudan, over its' five year duration. This reflection is supported by specific project data collected over the period of the project (2008-2014). The data collected included: (i) 6 monthly and annual donor reports; (ii) a mid-term internal and end of project independent evaluation of the entire project, and; (ii) a Ph.D study conducted by a member of the Sudanese research team. RESULTS: The ChRAIC project in Sudan achieved the deliverables set out at the beginning of the project. These included a national knowledge synthesis report on Sudan's health system; identification of country level health systems research priorities; research capacity assessment and skills training, and; the training and graduation of a Sudanese team member with a Ph.D. Mechanisms established in Sudan to facilitate these achievements included the adoption of culturally sensitive and locally specific research and capacity strengthening methods at district level; the signing of a Memorandum of Understanding at country level between the Ministry of Health, research and academic institutions in Sudan, and; the establishment of country level initiatives and a research unit. The latter being recognized globally through awards and membership in global health forums. CONCLUSION: We surmise that the 'network of action' approach adopted to partnership formation facilitated the benefits gained, but that adopting such an approach is not sufficient. More local and contextual factors influenced the extent of the benefits and the sustainability of the network. PMID- 27184908 TI - Female Sex Pheromone in Trails of the Minute Pirate Bug, Orius minutus (L). AB - Orius minutus (L.) (Heteroptera: Anthocoridae) is a natural enemy of agricultural pests such as thrips, aphids, and various newly hatched insect juveniles. In this study, we conducted 1) behavioral assays for evidence of contact sex pheromone activity in trails of O. minutus, and 2) chemical analysis to identify the essential chemical components of the trails. Males showed arrestment to trails of mature virgin females but not to trails from either conspecific nymphs or immature females. Females also showed arrestment to trails from conspecific males, although the response was weaker than that exhibited by males. The activity of female trails lasted for at least 46 h after deposition. Males showed a response irrespective of mating experience. Following confirmation that a contact sex pheromone was present in the trails of female O. minutus, we used a bioassay-driven approach to isolate the active chemicals. After fractionation on silica gel, the n-hexane fraction was found to be biologically active to males. A major compound in the active fraction was (Z)-9-nonacosene; this compound was found only in trail extracts of mature virgin females. Synthetic (Z)-9-nonacosene arrested O. minutus males, indicating that it is the major active component of the contact sex pheromone in the trails of female O. minutus. PMID- 27184909 TI - Hypertrophic Pachymeningitis With Optic Neuropathy Heralding Systemic Vasculitis. PMID- 27184911 TI - Locally advanced rectal cancers with simultaneous occurrence of KRAS mutation and high VEGF expression show invasive characteristics. AB - In this study, we investigated the mutation status of KRAS gene in pretherapeutic and preoperative biopsies in 63 specimens of locally advanced rectal cancers in order to evaluate its potential predictive and/or prognostic role. Regions of interest of KRAS exon 2 were amplified and visualized on 2% agarose gel. Obtained PCR products were subjected to direct sequencing. KRAS mutations were detected in 35% of patients, 91% of which were located in codon 12 and 9% in codon 13. In general, KRAS mutation status did not affect the response to neoadjuvant chemoradiotherapy (CRT). However, patients harboring mutated KRAS gene, simultaneously with high vascular endothelial growth factor (VEGF) expression, exhibited a worse response to CRT (p=0.030), a more frequent appearance of local recurrences and distant metastasis (p=0.003), and shorter overall survival (p=0.001) compared to all others. On the contrary, patients with GGT>GCT KRAS mutation exhibited a significantly better response to CRT than those with any other type of KRAS mutation (p=0.017). Moreover, the presence of GGT>GCT mutation was associated with low VEGF and Ki67 expression (p=0.012 in both cases), parameters related to less aggressiveness of the disease. Our results suggest that KRAS mutation status could have some predictive and prognostic importance in rectal cancer when analyzed together with other parameters, such as VEGF and Ki67 expression. In addition, it seems that not only the presence but the type of KRAS mutation is important for examining its impact on CRT response. PMID- 27184912 TI - Understanding the onset of oscillatory swimming in microchannels. AB - Self-propelled colloids (swimmers) in confining geometries follow trajectories determined by hydrodynamic interactions with the bounding surfaces. However, typically these interactions are ignored or truncated to the lowest order. We demonstrate that higher-order hydrodynamic moments cause rod-like swimmers to follow oscillatory trajectories in quiescent fluid between two parallel plates, using a combination of lattice-Boltzmann simulations and far-field calculations. This behavior occurs even far from the confining walls and does not require lubrication results. We show that a swimmer's hydrodynamic quadrupole moment is crucial to the onset of the oscillatory trajectories. This insight allows us to develop a simple model for the dynamics near the channel center based on these higher hydrodynamic moments, and suggests opportunities for trajectory-based experimental characterization of swimmers' hydrodynamic properties. PMID- 27184910 TI - beta-catenin is required in the neural crest and mesencephalon for pituitary gland organogenesis. AB - BACKGROUND: The pituitary gland is a highly vascularized tissue that requires coordinated interactions between the neural ectoderm, oral ectoderm, and head mesenchyme during development for proper physiological function. The interactions between the neural ectoderm and oral ectoderm, especially the role of the pituitary organizer in shaping the pituitary precursor, Rathke's pouch, are well described. However, less is known about the role of head mesenchyme in pituitary organogenesis. The head mesenchyme is derived from definitive mesoderm and neural crest, but the relative contributions of these tissues to the mesenchyme adjacent to the pituitary are not known. RESULTS: We carried out lineage tracing experiments using two neural crest-specific mouse cre lines, Wnt1-cre and P0-cre, and determined that the head mesenchyme rostral to the pituitary gland is neural crest derived. To assess the role of the neural crest in pituitary development we ablated it, using Wnt1-cre to delete Ctnnb1 (beta-catenin), which is required for neural crest development. The Wnt1-cre is active in the neural ectoderm, principally in the mesencephalon, but also in the posterior diencephalon. Loss of beta-catenin in this domain causes a rostral shift in the ventral diencephalon, including the pituitary organizer, resulting in pituitary dysmorphology. The neural crest deficient embryos have abnormally dilated pituitary vasculature due to a loss of neural crest derived pericytes. CONCLUSIONS: beta-catenin in the Wnt1 expression domain, including the neural crest, plays a critical role in regulation of pituitary gland growth, development, and vascularization. PMID- 27184913 TI - Redefining transfusion-related acute lung injury: don't throw the baby out with the bathwater. AB - Recently two articles have been published in TRANSFUSION in which the authors propose to change the current definition on transfusion-related acute lung injury (TRALI). It was proposed to view TRALI from the perspective of detectability versus nondetectability of leukoreactive alloantibodies (Transfusion 2015;55:1128 34). The authors argue that only cases in which leukoreactive alloantibodies can be detected should be defined as "true" TRALI in analogy with the understanding of the pathophysiology of heparin-induced thrombocytopenia. In the other article (Transfusion 2015;55:947-52), the authors propose to redefine possible TRALI to transfused acute respiratory distress syndrome (ARDS) as their study in intensive care unit patients did not show a relation between the number of transfusions and possible TRALI.We discuss these two propositions in light of the current evidence on pathophysiology of TRALI and possible TRALI. We argue that it is too early to redefine TRALI, as 1) factors, such as storage time of platelets, which induce TRALI in preclinical studies, have not yet been properly investigated in humans. Further research is needed on these agents before it is concluded that antibody mediated TRALI is the only "true" TRALI. 2) In light of the current knowledge, it makes perfect sense that multiple transfusion is not related to possible TRALI: ARDS risk factors in these patients result in a very sensitive equilibrium in which even only one transfusion induces TRALI. Excluding possible TRALI from the TRALI definition would result in further underrecognition of TRALI induced by alloantibodies and interferes with exclusion of donors related to TRALI cases and thus TRALI prevention. PMID- 27184914 TI - Determination and classification of the problems experienced by adults with single-sided deafness using ICF classification: an exploratory study using 26 participants. PMID- 27184915 TI - An Eruption of Disruption: The Changing Landscape of Both Teaching and Learning. PMID- 27184916 TI - Anorectal biofeedback for neurogenic bowel dysfunction in incomplete spinal cord injury. AB - STUDY DESIGN: A case-control study of prospectively collected data was performed. OBJECTIVES: To compare anorectal biofeedback (BF) outcomes in patients with incomplete motor spinal cord injury (SCI) and neurogenic bowel dysfunction (NBD) with a group of functional anorectal disorder-matched control patients. SETTING: Neurogastroenterology Unit affiliated with a Spinal Injury Unit in a tertiary referral centre in Sydney, Australia. METHODS: All consecutive patients with SCI and NBD referred for anorectal manometry and BF were matched in a 1:2 ratio with age, gender, parity and functional anorectal disorder-matched control patients. Instrumented BF was performed in six nurse-guided weekly visits. Outcomes included changes in anorectal physiology measures, symptom scores and quality-of life measures. RESULTS: Twenty-one patients were included. These were matched with 42 patient controls. Following BF, symptom scores improved significantly in both groups, as did effect of bowel disorder on quality of life. Improvement in these measures did not differ between the groups. Patients with SCI and NBD showed improvement in their sensory and motor anorectal function, including lowering of first sensation threshold and more effective balloon expulsion. CONCLUSIONS: Patients with incomplete motor SCI responded as well to anorectal BF as functional anorectal disorder-matched controls. Spinal cord-injured patients also showed improvement in anorectal sensorimotor dysfunction and balloon expulsion. These novel findings indicate that clinicians should not be dissuaded from considering behaviour-based therapeutic interventions such as anorectal BF in selected spinal cord-injured patients. PMID- 27184918 TI - Gross rainfall amount and maximum rainfall intensity in 60-minute influence on interception loss of shrubs: a 10-year observation in the Tengger Desert. AB - In water-limited regions, rainfall interception is influenced by rainfall properties and crown characteristics. Rainfall properties, aside from gross rainfall amount and duration (GR and RD), maximum rainfall intensity and rainless gap (RG), within rain events may heavily affect throughfall and interception by plants. From 2004 to 2014 (except for 2007), individual shrubs of Caragana korshinskii and Artemisia ordosica were selected to measure throughfall during 210 rain events. Various rainfall properties were auto-measured and crown characteristics, i.e., height, branch and leaf area index, crown area and volume of two shrubs were also measured. The relative interceptions of C. korshinskii and A. ordosica were 29.1% and 17.1%, respectively. Rainfall properties have more contributions than crown characteristics to throughfall and interception of shrubs. Throughfall and interception of shrubs can be explained by GR, RI60 (maximum rainfall intensities during 60 min), RD and RG in deceasing importance. However, relative throughfall and interception of two shrubs have different responses to rainfall properties and crown characteristics, those of C. korshinskii were closely related to rainfall properties, while those of A. ordosica were more dependent on crown characteristics. We highlight long-term monitoring is very necessary to determine the relationships between throughfall and interception with crown characteristics. PMID- 27184917 TI - The Pediatric Measure of Participation (PMoP) short forms. AB - STUDY DESIGN: Multi-center cross-sectional cohort study. OBJECTIVES: The objectives of this study were to develop and validate short forms (SFs) of participation for child- and parent-reported outcomes following spinal cord injury (SCI). SETTING: Three pediatric orthopedic hospitals in the United States. METHODS: The expert panel used calibration data from the pediatric computerized adaptive test (CAT) development study (convenience sample of 381 children and adolescents with SCI and 322 parents or caregivers) to select SF items. The panel selected items for two domains (participation self-relevant to what I want to do; participation friends-relevant to what my friends do), with parent and child versions for each domain. Psychometric analyses included group reliability, Cronbach's alpha, agreement (SFs and item banks), percent of sample with highest (ceiling) and lowest (floor) scores by level of lesion (paraplegia/tetraplegia), and test information function. RESULTS: Group reliability and Cronbach's alpha values are acceptable (0.74-0.92) and agreement (intraclass correlation coefficients for SFs and total item banks) is strong (0.89-0.95). Floor effects were minimal for people with tetraplegia and paraplegia (0-1.19%). Ceiling effects were minimal for people with tetraplegia (0-3.13%) and slightly higher, but acceptable, for people with paraplegia (8.06-14.02%). Test information function for the SFs was sufficiently high over the range of scores for the majority of the sample. CONCLUSION: Pediatric Measure of Participation (PMoP) SFs are acceptable for use when CATs are not feasible. SPONSORSHIP: The study was funded by the Shriners Hospitals for Children Research Grant 79142 (Mulcahey, PI) and the Boston ROC Grant 5R24HD065688-05 (Jette, PI). PMID- 27184919 TI - 18F-FDG positron emission tomography in oncology: main indications. AB - The development of molecular and functional imaging with new imaging techniques such as computed tomography, magnetic resonance imaging, and positron emission tomography (PET) among others, has greatly improved the detection of tumors, tumor staging, and the detection of possible recurrences. Furthermore, the combination of these different imaging modalities and the continual development of radiotracers for PET have advanced our understanding and knowledge of the different pathophysiological processes in cancer, thereby helping to make treatment more efficacious, improving patients' quality of life, and increasing survival. PET is one of the imaging techniques that has attracted the most interest in recent years for its diagnostic capabilities. Its ability to anatomically locate pathologic foci of metabolic activity has revolutionized the detection and staging of many tumors, exponentially broadening its potential indications not only in oncology but also in other fields such as cardiology, neurology, and inflammatory and infectious diseases. PMID- 27184920 TI - Preventing High Fat Diet-induced Obesity and Improving Insulin Sensitivity through Neuregulin 4 Gene Transfer. AB - Neuregulin 4 (NRG4), an epidermal growth factor-like signaling molecule, plays an important role in cell-to-cell communication during tissue development. Its function to regulate energy metabolism has recently been reported. This current study was designed to assess the preventive and therapeutic effects of NRG4 overexpression on high fat diet (HFD)-induced obesity. Using the hydrodynamic gene transfer method, we demonstrate that Nrg4 gene transfer in mice suppressed the development of diet-induced obesity, but did not affect pre-existing adiposity and body weight in obese mice. Nrg4 gene transfer curbed HFD-induced hepatic steatosis by inhibiting lipogenesis and PPARgamma-mediated lipid storage. Concurrently, overexpression of NRG4 reduced chronic inflammation in both preventive and treatment studies, evidenced by lower mRNA levels of macrophage marker genes including F4/80, Cd68, Cd11b, Cd11c, and macrophage chemokine Mcp1, resulting in improved insulin sensitivity. Collectively, these results demonstrate that overexpression of the Nrg4 gene by hydrodynamic gene delivery prevents HFD-induced weight gain and fatty liver, alleviates obesity-induced chronic inflammation and insulin resistance, and supports the health benefits of NRG4 in managing obesity and obesity-associated metabolic disorders. PMID- 27184922 TI - A novel chemo-mechano-biological model of arterial tissue growth and remodelling. AB - Arterial growth and remodelling (G&R) is mediated by vascular cells in response to their chemical and mechanical environment. To date, mechanical and biochemical stimuli tend to be modelled separately, however this ignores their complex interplay. Here, we present a novel mathematical model of arterial chemo-mechano biology. We illustrate its application to the development of an inflammatory aneurysm in the descending human aorta. The arterial wall is modelled as a bilayer cylindrical non-linear elastic membrane, which is internally pressurised and axially stretched. The medial degradation that accompanies aneurysm development is driven by an inflammatory response. Collagen remodelling is simulated by adaption of the natural reference configuration of constituents; growth is simulated by changes in normalised mass-densities. We account for the distribution of attachment stretches that collagen fibres are configured to the matrix and, innovatively, allow this distribution to remodel. This enables the changing functional role of the adventitia to be simulated. Fibroblast-mediated collagen growth is represented using a biochemical pathway model: a system of coupled non-linear ODEs governs the evolution of fibroblast properties and levels of key biomolecules under the regulation of Transforming Growth Factor (TGF) beta, a key promoter of matrix deposition. Given physiologically realistic targets, different modes of aneurysm development can be captured, while the predicted evolution of biochemical variables is qualitatively consistent with trends observed experimentally. Interestingly, we observe that increasing the levels of collagen-promoting TGF-beta results in arrest of aneurysm growth, which seems to be consistent with experimental evidence. We conclude that this novel Chemo-Mechano-Biological (CMB) mathematical model has the potential to provide new mechanobiological insight into vascular disease progression and therapy. PMID- 27184923 TI - Effectiveness of caudal septal extension graft application in endonasal septoplasty. AB - INTRODUCTION: Septal deviation is a common disease seen in daily otorhinolaryngology practice and septoplasty is a commonly performed surgical procedure. Caudal septum deviation is also a challenging pathology for ear, nose, and throat specialists. Many techniques are defined for caudal septal deviation. OBJECTIVE: To evaluate the effectiveness of caudal septal extension graft (CSEG) application in patients who underwent endonasal septoplasty for a short and deviated nasal septum. METHODS: Forty patients with nasal septal deviation, short nasal septum, and weak nasal tip support who underwent endonasal septoplasty with or without CSEG placement between August 2012 and June 2013 were enrolled in this study. Twenty patients underwent endonasal septoplasty with CSEG placement. The rest of the group, who rejected auricular or costal cartilage harvest for CSEG placement, underwent only endonasal septoplasty without any additional intervention. Using the Nasal Obstruction Symptom Evaluation (NOSE) and Rhinoplasty Outcome Evaluation (ROE) questionnaires, pre- and post-operative acoustic rhinometer measurements were evaluated to assess the effect of CESG placement on nasal obstruction. RESULTS: In the control group, preoperative and postoperative minimal cross-sectional areas (MCA1) were 0.44+/-0.10cm2 and 0.60+/ 0.11cm2, respectively (p<0.001). In the study group, pre- and postoperative MCA1 values were 0.45+/-0.16cm2 and 0.67+/-0.16cm2, respectively (p<0.01). In the control group, the nasal cavity volume (VOL1) value was 1.71+/-0.21mL preoperatively and 1.94+/-0.17mL postoperatively (p<0.001). In the study group, pre- and postoperative VOL1s were 1.72+/-0.15mL and 1.97+/-0.12mL, respectively (p<0.001). Statistical analysis of postoperative MCA1 and VOL1 values in the study and the control groups could not detect any significant intergroup difference (p=0.093 and 0.432, respectively). In the study group, mean nasolabial angles were 78.15+/-4.26 degrees and 90.70+/-2.38 degrees , respectively (p<0.001). CONCLUSION: Endonasal septoplasty with CESG placement is an effective surgical procedure with minimal complication rate for subjects who have a deviated, short nasal septum and weak nasal tip support. PMID- 27184921 TI - DNA Methylation Signatures of Early Childhood Malnutrition Associated With Impairments in Attention and Cognition. AB - BACKGROUND: Early childhood malnutrition affects 113 million children worldwide, impacting health and increasing vulnerability for cognitive and behavioral disorders later in life. Molecular signatures after childhood malnutrition, including the potential for intergenerational transmission, remain unexplored. METHODS: We surveyed blood DNA methylomes (~483,000 individual CpG sites) in 168 subjects across two generations, including 50 generation 1 individuals hospitalized during the first year of life for moderate to severe protein-energy malnutrition, then followed up to 48 years in the Barbados Nutrition Study. Attention deficits and cognitive performance were evaluated with the Connors Adult Attention Rating Scale and Wechsler Abbreviated Scale of Intelligence. Expression of nutrition-sensitive genes was explored by quantitative reverse transcriptase polymerase chain reaction in rat prefrontal cortex. RESULTS: We identified 134 nutrition-sensitive, differentially methylated genomic regions, with most (87%) specific for generation 1. Multiple neuropsychiatric risk genes, including COMT, IFNG, MIR200B, SYNGAP1, and VIPR2 showed associations of specific methyl-CpGs with attention and IQ. IFNG expression was decreased in prefrontal cortex of rats showing attention deficits after developmental malnutrition. CONCLUSIONS: Early childhood malnutrition entails long-lasting epigenetic signatures associated with liability for attention and cognition, and limited potential for intergenerational transmission. PMID- 27184925 TI - Interactions between cannabinoid receptor agonists and mu opioid receptor agonists in rhesus monkeys discriminating fentanyl. AB - Cannabinoid receptor agonists such as delta-9-tetrahydrocannabinol (Delta(9)-THC) enhance some (antinociceptive) but not other (positive reinforcing) effects of mu opioid receptor agonists, suggesting that cannabinoids might be combined with opioids to treat pain without increasing, and possibly decreasing, abuse. The degree to which cannabinoids enhance antinociceptive effects of opioids varies across drugs insofar as Delta(9)-THC and the synthetic cannabinoid receptor agonist CP55940 increase the potency of some mu opioid receptor agonists (e.g., fentanyl) more than others (e.g., nalbuphine). It is not known whether interactions between cannabinoids and opioids vary similarly for other (abuse related) effects. This study examined whether Delta(9)-THC and CP55940 differentially impact the discriminative stimulus effects of fentanyl and nalbuphine in monkeys (n=4) discriminating 0.01mg/kg of fentanyl (s.c.) from saline. Fentanyl (0.00178-0.0178mg/kg) and nalbuphine (0.01-0.32mg/kg) dose dependently increased drug-lever responding. Neither Delta(9)-THC (0.032 1.0mg/kg) nor CP55940 (0.0032-0.032mg/kg) enhanced the discriminative stimulus effects of fentanyl or nalbuphine; however, doses of Delta(9)-THC and CP55940 that shifted the nalbuphine dose-effect curve markedly to the right and/or down were less effective or ineffective in shifting the fentanyl dose-effect curve. The mu opioid receptor antagonist naltrexone (0.032mg/kg) attenuated the discriminative stimulus effects of fentanyl and nalbuphine similarly. These data indicate that the discriminative stimulus effects of nalbuphine are more sensitive to attenuation by cannabinoids than those of fentanyl. That the discriminative stimulus effects of some opioids are more susceptible to modification by drugs from other classes has implications for developing maximally effective therapeutic drug mixtures with reduced abuse liability. PMID- 27184924 TI - Catheter-based Intramyocardial Injection of FGF1 or NRG1-loaded MPs Improves Cardiac Function in a Preclinical Model of Ischemia-Reperfusion. AB - Cardiovascular protein therapeutics such as neuregulin (NRG1) and acidic fibroblast growth factor (FGF1) requires new formulation strategies that allow for sustained bioavailability of the drug in the infarcted myocardium. However, there is no FDA-approved injectable protein delivery platform due to translational concerns about biomaterial administration through cardiac catheters. We therefore sought to evaluate the efficacy of percutaneous intramyocardial injection of poly(lactic-co-glycolic acid) microparticles (MPs) loaded with NRG1 and FGF1 using the NOGA MYOSTAR injection catheter in a porcine model of ischemia-reperfusion. NRG1- and FGF1-loaded MPs were prepared using a multiple emulsion solvent-evaporation technique. Infarcted pigs were treated one week after ischemia-reperfusion with MPs containing NRG1, FGF1 or non-loaded MPs delivered via clinically-translatable percutaneous transendocardial-injection. Three months post-treatment, echocardiography indicated a significant improvement in systolic and diastolic cardiac function. Moreover, improvement in bipolar voltage and decrease in transmural infarct progression was demonstrated by electromechanical NOGA-mapping. Functional benefit was associated with an increase in myocardial vascularization and remodeling. These findings in a large animal model of ischemia-reperfusion demonstrate the feasibility and efficacy of using MPs as a delivery system for growth factors and provide strong evidence to move forward with clinical studies using therapeutic proteins combined with catheter-compatible biomaterials. PMID- 27184926 TI - Crystallization behavior of iron-based amorphous nanoparticles prepared sonochemically. AB - In general, a rapid quenching is required to obtain an amorphous metal. It is known that an intensive ultrasonication generates a very high temperature within cavitation bubbles in a very short moment, which enables a rapid quenching process in a liquid phase synthesis. In this study, the sonochemically-derived "amorphous iron" from Fe(CO)5 was carefully examined by XRD, TEM, TG-DTA. The product was found to be an amorphous containing a certain amount (~15%) of volatile component that can be removed by heating in a nitrogen flow. After annealed in the inert atmosphere at 600 degrees C, cooled down to room temperature, and then exposed in air (oxygen), the sample showed a strong exotherm accompanied by a weight gain. This is due to oxidation of fine metallic iron. Experimental operations of such a reactive material were examined. PMID- 27184928 TI - Head shaking in the forced swim test: A robust but unexplored sex difference. AB - Preclinical psychopharmacology research needs novel behavioral indices and improved animal models for both sexes. The forced swim test (FST) is the most popular test for screening antidepressant potential. Sex differences in FST behaviors, such as immobility and swimming, are not consistent among laboratories. Reliable indices, sensitive to sex differences, are required. We identified a robust sex difference in the frequency of headshakes during the standard two session FST, with male rats exhibiting higher number of head shakes than females. Furthermore, we explored whether strain, ageing, sex- and stress hormone levels influence this sex difference. Experiments in middle-aged and senescent Wistar rats, as well as in gonadectomized and adrenalectomized with corticosterone replacement young adult males and females, revealed that sex differences in headshakes during FST are not influenced by age or corticosterone, but are abolished following castration of male rats. Interestingly, headshake frequency correlated positively with testosterone, but not corticosterone levels. Finally, testing of Flinders Sensitive Line (FSL) and Sprague-Dawley (SD) rats in a single 5min FST session revealed that headshake frequency is sensitive to antidepressant treatment with female rats exhibiting opposite responses to treatment than male FSL rats. Mirtazapine, a 5-HT2 antagonist, enhanced headshakes in females and decreased them in male FSL rats. Based on current data and the available literature, sex differences in headshake frequency should be linked to analogous sex differences in serotonin receptors. Headshake frequency during the FST is an additional valuable behavioral index, sensitive to sex differences, gonadal hormones and antidepressants modulating serotonin receptors. PMID- 27184929 TI - AAOM Clinical Practice Statement: Subject: Oral Contact Allergy. PMID- 27184927 TI - The Hippo effector TAZ (WWTR1) transforms myoblasts and TAZ abundance is associated with reduced survival in embryonal rhabdomyosarcoma. AB - The Hippo effector YAP has recently been identified as a potent driver of embryonal rhabdomyosarcoma (ERMS). Most reports suggest that the YAP paralogue TAZ (gene symbol WWTR1) functions as YAP but, in skeletal muscle, TAZ has been reported to promote myogenic differentiation, whereas YAP inhibits it. Here, we investigated whether TAZ is also a rhabdomyosarcoma oncogene or whether TAZ acts as a YAP antagonist. Immunostaining of rhabdomyosarcoma tissue microarrays revealed that TAZ is significantly associated with poor survival in ERMS. In 12% of fusion gene-negative rhabdomyosarcomas, the TAZ locus is gained, which is correlated with increased expression. Constitutively active TAZ S89A significantly increased proliferation of C2C12 myoblasts and, importantly, colony formation on soft agar, suggesting transformation. However, TAZ then switches to enhance myogenic differentiation in C2C12 myoblasts, unlike YAP. Conversely, lentiviral shRNA-mediated TAZ knockdown in human ERMS cells reduced proliferation and anchorage-independent growth. While TAZ S89A or YAP1 S127A similarly activated the 8XGTIIC-Luc Hippo reporter, only YAP1 S127A activated the Brachyury (T-box) reporter. Consistent with its oncogene function, TAZ S89A induced expression of the ERMS cancer stem cell gene Myf5 and the serine biosynthesis pathway (Phgdh, Psat1, Psph) in C2C12 myoblasts. Thus, TAZ is associated with poor survival in ERMS and could act as an oncogene in rhabdomyosarcoma. (c) 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. PMID- 27184930 TI - Utility of the HAS-BLED Score in Risk Stratifying Patients on Dual Antiplatelet Therapy Post 12 Months After Drug-Eluting Stent Placement. AB - INTRODUCTION: Current guidelines recommend continuation of dual anti-platelet therapy (DAPT) for 12 months after percutaneous coronary intervention (PCI). Recent studies have shown benefit in continuing DAPT beyond 12 months but at the risk of increase bleeding. To date, there has been little data on risk stratifying patients to determine who can continue DAPT beyond 12 months at minimal bleeding risk. METHODS: All patients who underwent drug-eluting stent (DES) placement from January 1, 2013 to September 30, 2014 were reviewed. Patients who had follow-up for at least 12 months, placement of 2nd generation everolimus-coated DES, and were on DAPT for at least 12 months were included. Patients with a history of atrial fibrillation, follow-up time less than 12 months, or were on concurrent oral anticoagulation therapy were excluded. RESULTS: Five hundred thirty-one patients were analyzed as described above. Two hundred two patients included in our study with 7 patients in the bleeding cohort and 195 patients in no-bleed cohort. The HAS-BLED score in patients who had a bleeding episode vs. those who did not was 3.29 vs. 2.24 (P value of 0.0009). Although not statistically significant, patients who had a bleeding episode were more likely to have renal dysfunction, alcohol use, be on prasugrel, and be on 325mg of aspirin. CONCLUSION: The study shows that the HAS-BLED score can be of utility in risk stratifying patients in determining who can continue DAPT beyond 12 months. Furthermore, a HAS-BLED score of less than 2 may help guide extended DAPT beyond 12 months at minimal bleeding risk. (c) 2016 Wiley Periodicals, Inc. PMID- 27184931 TI - Is there any range-of-motion advantage to using bearings larger than 36mm in primary hip arthroplasty: A case-control study comparing 36-mm and large-diameter heads. AB - BACKGROUND: Large-diameter (>36mm) total hip arthroplasty (THA) has developed rapidly since the advent of ceramic-on-ceramic (CoC) bearings and highly cross linked polyethylene. Theoretically, the increase in diameter reduces the risk of instability, although the advantage of calibers beyond 36mm has not been demonstrated in terms of range-of-motion recovery. We conducted a comparative study with a single prosthesis model to determine whether increasing the caliber beyond 36mm provides: (1) better recovery of range-of-motion, (2) a higher functional score, and (3) reduction of the dislocation rate. HYPOTHESIS: Increasing the range-of-motion by increasing the caliber beyond 36mm provides better range-of-motion. MATERIAL AND METHODS: We analyzed two consecutive, single operator cementless THA series performed via the mini posterior approach, which differed only in the bearing system (51 metal-on-metal [MoM] with a mean caliber of 45mm+/-3.3 [range, 40-54] and 61 CoC with a 36-mm caliber). Both series were comparable preoperatively in terms of age, diagnosis, functional scores, preoperative range-of-motion, body mass index, UCLA activity level, and Charnley score. We compared the joint range of movement at follow-up and the gains in range of movement, onset of dislocation, and functional scores (Oxford, Postel Merle d'Aubigne [PMA]). RESULTS: The mean overall joint range-of-motion was 254 degrees +/-39 degrees (range, 150-310 degrees ) for an 81 degrees +/-44 degrees (range, -50 to 180 degrees ) gain in the MoM group and 256 degrees +/-23 degrees (range, 200-280 degrees ) for an 84 degrees +/-40 degrees (range, 0-160 degrees ) gain in the CoC group (NS). The MoM group presented the following results: Oxford=13.71+/-3.66 (range, 12-33) for a gain of 24.82 points+/-7.9 (range, -1 to 40), PMA=17.75+/-1.06 (range, 11-18) for a gain of 7.78 points+/-4.01 (range, 2 15). The CoC group had: Oxford=14.98+/-4.42 (range, 12-36) for a gain of 24.75 points+/-6.55 (range, 12-40), PMA 17.66+/-0.7 (range, 14-18) for a gain of 8 points+/-3.77 (range, 1-15). None of the gains and scores at follow-up differed significantly between the two groups. No episode of dislocation was identified. DISCUSSION: The current trend of increasing femoral head diameters beyond 36mm to improve the gains in joint range-of-motion and function is not warranted. The potential side effects of increasing the caliber call for even greater caution in the use of large-diameter heads because our hypothesis has not been confirmed. LEVEL OF EVIDENCE: Case-control study, level III. PMID- 27184932 TI - High expression of integrin beta6 in association with the Rho-Rac pathway identifies a poor prognostic subgroup within HER2 amplified breast cancers. AB - Integrin alphavbeta6 is involved in the transition from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) of the breast. In addition, integrin beta6 (ITGB6) is of prognostic value in invasive breast cancers, particularly in HER2+ subtype. However, pathways mediating the activity of integrin alphavbeta6 in clinical progression of invasive breast cancers need further elucidation. We have examined human breast cancer specimens (N = 460) for the expression of integrin beta6 (ITGB6) mRNA by qPCR. In addition, we have examined a subset (N = 147) for the expression of alphavbeta6 integrin by immunohistochemistry (IHC). The expression levels of members of Rho-Rac pathway including downstream genes (ACTR2, ACTR3) and effector proteinases (MMP9, MMP15) were estimated by qPCR in the HER2+ subset (N = 59). There is a significant increase in the mean expression of ITGB6 in HER2+ tumors compared to HR+HER2- and triple negative (TNBC) subtypes (P = 0.00). HER2+ tumors with the highest levels (top quartile) of ITGB6 have significantly elevated levels of all the genes of the Rho-Rac pathway (P-values from 0.01 to 0.0001). Patients in this group have a significantly shorter disease free survival compared to the group with lower ITGB6 levels (HR = 2.9 (0.9-8.9), P = 0.05). The mean level of ITGB6 expression is increased further in lymph node positive tumors. The increased regional and distant metastasis observed in HER2+ tumors with high levels of ITGB6 might be mediated by the canonical Rho-Rac pathway through increased expression of MMP9 and MMP15. PMID- 27184934 TI - Sources of sporadic Pseudomonas aeruginosa colonizations/infections in surgical ICUs: Association with contaminated sink trap. AB - BACKGROUND: Many studies have reported the hospital outbreaks of Pseudomonas aeruginosa due to cross-contamination between patients and water fittings, but the importance of water fittings as sources of sporadic P. aeruginosa colonizations/infections remains ambiguous. AIM: To investigate the sources of sporadic P. aeruginosa colonizations/infections in a clinical intensive surveillance, and further analysis the potential of sink trap for P. aeruginosa transmission in intensive care units (ICUs). METHODS: Patients monitoring and targeted environmental screening for P. aeruginosa was performed prospectively over a 27-week period, in absence of recognized outbreak, in two surgical intensive care units (SICUs). All isolates were genotyped by Pulsed field gel electrophoresis analysis. FINDINGS: 18.9% (46/244) of water fitting samples harbored P. aeruginosa, and active screening samples from 9.2% (55/595) of hospitalized patients carried with P. aeruginosa. According to genotype results, approximately 50% of P. areuginosa colonizations/infections of patients were of exogenous origin. 64.7% (11/17) of exogenous sourced cases were associated with contaminated sink traps. There was a significant correlation between the incidence of exogenous colonization/infection and the prevalence of P. areuginosa in water fitting in SICU-2 (rs = 0.972; p = 0.014). Furthermore, P. areuginosa from sink trap possessed a higher level of resistance to multi-antibiotics as opposed to cross-transmission from other patients. CONCLUSION: Water fitting especially sink trap act as an important role in sporadic P. aeruginosa transmission in SICU patients. This report highlights the necessity of identification of potential environmental reservoirs, such as sinks, for control of infections of environmentally hardy multi-resistant P. areuginosa. PMID- 27184933 TI - Balancing intestinal and systemic inflammation through cell type-specific expression of the aryl hydrocarbon receptor repressor. AB - As a sensor of polyaromatic chemicals the aryl hydrocarbon receptor (AhR) exerts an important role in immune regulation besides its requirement for xenobiotic metabolism. Transcriptional activation of AhR target genes is counterregulated by the AhR repressor (AhRR) but the exact function of the AhRR in vivo is currently unknown. We here show that the AhRR is predominantly expressed in immune cells of the skin and intestine, different from other AhR target genes. Whereas AhRR antagonizes the anti-inflammatory function of the AhR in the context of systemic endotoxin shock, AhR and AhRR act in concert to dampen intestinal inflammation. Specifically, AhRR contributes to the maintenance of colonic intraepithelial lymphocytes and prevents excessive IL-1beta production and Th17/Tc17 differentiation. In contrast, the AhRR enhances IFN-gamma-production by effector T cells in the inflamed gut. Our findings highlight the physiologic importance of cell-type specific balancing of AhR/AhRR expression in response to microbial, nutritional and other environmental stimuli. PMID- 27184935 TI - A case of lobar pneumonia and sepsis with death caused by invasive Klebsiella rhinoscleromatis infection. AB - Klebsiella pneumoniae often causes pneumonia and other infections in heavy drinkers and patients with diabetes. Pneumonia caused by Klebsiella rhinoscleromatis, a subspecies of K. pneumoniae, has not been previously reported. We report a case of pneumonia caused by K. rhinoscleromatis. A 68-year old man with type 2 diabetes visited our department complaining fever and fatigue for 10 days and cough and bloody sputum for two days. His Japan Coma Scale score was I-1, body temperature 38.3 degrees C, blood pressure 85/51 mmHg, pulse 135 bpm, and peripheral capillary oxygen saturation level 92% (room air). He had no abnormal breathing sounds. His white blood cell count had decreased to 2600/MUL, and his C-reactive protein level was high, at 35.9 mg/dL. Chest computed tomography revealed lobar pneumonia in the right upper lobe and pneumonia in the left upper division. Klebsiella was suspected based on the result of a sputum smear examination. He was diagnosed with septic shock due to pneumonia and was immediately admitted. Intravenous antibacterial (levofloxacin) treatment was initiated, however, he died 13 h after presenting at the hospital. Subsequently, K. rhinoscleromatis was detected in sputum and blood culture. Additional testing determined the bacteria to be a highly pathogenic hypermucoviscosity phenotype and the cause of the fatal lobar pneumonia. Although cases of rhinoscleroma and bacteremia caused by K. rhinoscleromatis infection have been reported, this is the first report of a case with sepsis caused by fulminant pneumonia. PMID- 27184936 TI - Diagnostic value of levels of presepsin (soluble CD14-subtype) in febrile neutropenia in patients with hematological disorders. AB - BACKGROUND: Whether presepsin (soluble CD14-subtype) is better than other markers including procalcitonin (PCT), has not been adequately investigated in febrile neutropenia (FN). METHODS: We prospectively examined the utility of presepsin in FN in Cohort 1 (C1) and 2 (C2), between November 2010 and February 2012, and between November 2013 and January 2014, respectively. The purpose of this study was to investigate 1) the relative value of serum presepsin over serum PCT in C1, and 2) the relative value of plasma presepsin as compared with serum PCT, C reactive protein, interleukin-6 and interleukin-8 with frequent, repeated sampling in C2. RESULTS: Seventy-nine FN episodes (C1, 75; C2, 4) were evaluable. In C1, when compared with control values, presepsin was significantly higher at onset of FN (P = 0.004), while PCT was not significantly higher (P = 0.54). The median value of serum presepsin within 72 h of onset of FN in subjects with fever of unknown origin, local infection, bacteremia and septic shock was 680 (reference 314) pg/ml, 763, 782 and 1359, respectively. In C2, the mean levels of plasma presepsin from onset of FN to 72 h were classified as negative in the two patients with no suspected site of infection, and those of the remaining two patients with clinically probable infections were positive (175, 131, 346 and 329 pg/ml, respectively). In contrast, the other markers did not discriminate between this two groups. CONCLUSIONS: In FN, presepsin may be an earlier and more sensitive indicator of bacterial infection than PCT. PMID- 27184937 TI - Development of the 19 X-STR loci multiplex system and genetic analysis of a Zhejiang Han population in China. AB - The 19 X-STRs multiplex system is a PCR-based amplification kit that facilitates simultaneous amplification of 19 X-chromosomal STR loci (i.e. DXS7423, DXS10148, DXS10159, DXS6809, DXS7424, DXS8378, DXS10164, DXS10162, DXS7132, DXS10079, DXS6789, DXS101, DXS10103,DXS10101, HPTRB, DXS10075, DXS10074, DXS10135, and DXS10134). Eleven loci were extensively used in an Investigator Qiagen Argus X-12 (DXS7423, DXS10148, DXS8378, DXS10162, DXS7132, DXS10079, DXS10103, DXS10101, HPTRB, DXS10074, and DXS10135). In this research, the multiplex system was tested for detection sensitivity, DNA mixtures, inhibitor tolerance and species specificity; SWGDAM Validation Guidelines - Approved December 2012 were followed for the human fluorescent STR multiplex PCR reagent. Samples from 181 unrelated Zhejiang Han individuals (121 males and 60 females) were typed using this multiplex system. The results show that this 19X-STRs multiplex system is a robust and reliable amplification means to facilitate forensic and human identification testing. PMID- 27184938 TI - Determination of the optimal sample size for a clinical trial accounting for the population size. AB - The problem of choosing a sample size for a clinical trial is a very common one. In some settings, such as rare diseases or other small populations, the large sample sizes usually associated with the standard frequentist approach may be infeasible, suggesting that the sample size chosen should reflect the size of the population under consideration. Incorporation of the population size is possible in a decision-theoretic approach either explicitly by assuming that the population size is fixed and known, or implicitly through geometric discounting of the gain from future patients reflecting the expected population size. This paper develops such approaches. Building on previous work, an asymptotic expression is derived for the sample size for single and two-arm clinical trials in the general case of a clinical trial with a primary endpoint with a distribution of one parameter exponential family form that optimizes a utility function that quantifies the cost and gain per patient as a continuous function of this parameter. It is shown that as the size of the population, N, or expected size, N* in the case of geometric discounting, becomes large, the optimal trial size is O(N1/2) or O(N*1/2). The sample size obtained from the asymptotic expression is also compared with the exact optimal sample size in examples with responses with Bernoulli and Poisson distributions, showing that the asymptotic approximations can also be reasonable in relatively small sample sizes. PMID- 27184940 TI - Determination of lead, cadmium and nickel in hennas and other hair dyes sold in Turkey. AB - The concentrations of lead, nickel and cadmium in various hennas and synthetic hair dyes were determined by high-resolution continuum source graphite furnace atomic absorption spectrometry (HR-CS GFAAS). For this purpose, 1 g of sample was digested using 4 mL of hydrogen peroxide (30%) and 8 mL of nitric acid (65%). The digests were diluted to 15 mL and the analytes were determined by HR-CS GFAAS. All determinations of Pb and Cd were performed using NH4H2PO4 as a modifier. The analytes in hair certified reference materials (CRMs) were found within the uncertainty limits of the certified values. In addition, the analyte concentrations added to hair dye were recovered between 95 and 110%. The limits of detection of the method were 48.90, 3.90 and 12.15 ng g(-1) for Pb, Cd and Ni, respectively and the characteristic concentrations were 8.70, 1.42 and 6.30 ng g( 1), respectively. Finally, the concentrations of the three analytes in various synthetic hair dyes with different brands, shades and formulae as well as in two henna varieties were determined using aqueous standards for calibration. The concentrations of Pb, Cd and Ni in hair dyes were in the ranges of LOD-0.56 MUg g(-1), LOD-0.011 ng g(-1) and 0.030-0.37 MUg g(-1), respectively, whereas those in the two hennas were 0.60-0.93 MUg g(-1), 0.033-0.065 ng g(-1) and 0.49-1.06 MUg g(-1), respectively. PMID- 27184939 TI - Probabilistic Monte Carlo estimation for quantitative exposure assessment of lotion transfer via baby wipes usage. AB - Unique aspects of childhood exposure to products need childs specific exposure data. This study developed a probabilistic exposure model for lotion transfer to diapered skin through normal use of baby wipes in children up to 48 months of age. Monte Carlo simulations used baby wipe diary data from the US, Germany and the UK, body weight data from the US, and lotion transfer data from single and multiple wipes adjusting for separate diaper changes. The models predicted a declining number of wipes used/day with a reduction in lotion transfer as age and body weight increased. Experimental testing on multiple sequential wipes used on an overlapping area showed a reduction in lotion deposition by 23.9% after the first wipe. Overall, the weighted population average over the approximate diapering period of 0-36 months across the three geographies at 50th, 90th, & 95th percentiles, were between 130, 230, 260 mg/kg/day, respectively, and 150, 270, 310 mg/kg/day depending on whether a reduction due to overlap is implemented. The statistical model represents an effective strategy to determine exposure to baby wipes lotion for exposure based risk assessment. PMID- 27184942 TI - Science in Focus: MicroRNA in Glioma - Potential as Biomarkers and Therapeutic Targets. PMID- 27184941 TI - Current Views on Clinical Oncology Training from the 2015 Oncology Registrars' Forum Survey. AB - The major role of the Oncology Registrars' Forum (ORF) of the Royal College of Radiologists is to voice the opinions of the clinical oncology trainee body and work towards improving all aspects of clinical oncology training in the UK. In order to provide data to support these efforts, the ORF undertakes a biennial survey of all trainees. As with the previous surveys, this year's ORF survey produced data that highlight areas of good training as well as new and ongoing areas of concern. This summary highlights the key survey results and provides recommendations for improving the delivery of clinical oncology training in the UK. PMID- 27184943 TI - Acute and Late Genitourinary Toxicity after 72 Gy of Conventionally Fractionated Conformal Radiotherapy for Localised Prostate Cancer: Impact of Individual and Clinical Parameters. AB - AIM: Our aim was to estimate the incidence of acute and late genitourinary toxicity in patients treated with three-dimensional conformal radiotherapy (3DCRT) for localised prostate cancer and to estimate the possible influence of individual and clinical characteristics. MATERIALS AND METHODS: Between September 2009 and September 2013, 225 patients with localised prostate cancer were treated with 3DCRT. Ninety-four patients with an estimated risk of lymph node involvement <=15%, according to the Roach formula, were evaluated in this study. All patients received a total dose of 72 Gy in 36 fractions. Acute and late genitourinary toxicity were graded according to the European Organization for Research and Treatment of Cancer radiation morbidity scoring scale. Characteristics such as age, smoking status, previous abdominal or pelvic surgery (PAPS), diabetes mellitus and the use of diuretics were analysed as possible predictive factors of toxicity. The median follow-up was 27 months. RESULTS: Grade >=2 acute toxicity during 3DCRT developed in 25 of 94 patients (26.5%). Predictive factors of acute genitourinary toxicity grade >=2 in the multivariate logistic regression analysis (MVA) were current smoking status (P = 0.003), PAPS (P = 0.012) and the use of diuretics (P = 0.017). The 2 and 3 year cumulative risk of late genitourinary toxicity grade >=1 was 25.3% and 30.2%, respectively. In the MVA, acute genitourinary toxicity was significantly associated with late genitourinary toxicity (P = 0.024). CONCLUSION: Current smoking status, PAPS and the use of diuretics have a significant effect on the occurrence of acute genitourinary toxicity grade >=2. The occurrence of any grade of acute genitourinary toxicity has a significant influence on the development of any grade of late genitourinary toxicity. PMID- 27184944 TI - Sustained responses after clofarabine-based sequential allogeneic stem cell transplantation in children with high-risk, relapse and/or refractory acute myeloid leukemia or juvenile myelomonocytic leukemia: a study on behalf of the French society of bone marrow transplantation or cell therapy (SFGM-TC). PMID- 27184945 TI - Short-term ventricular assist device as a bridge to decision in cardiogenic shock: is it a justified strategy? AB - PURPOSE: Low cardiac output syndrome is associated with significant mortality. In patients with refractory low cardiac output left ventricular assist devices (VAD) are used to re-establish cardiac output and to prevent death. However, long-term LVAD implantation in these is complicated by a high rate of right heart failure and mortality. Therefore, our strategy is to implant a short-term VAD (left or biventricular) as a bridge to decission. METHODS: We retrospectively analysed data from 66 patients who received a short-term LVAD support prior to implantation of a long-term LVAD or HTx between 2003 and 2014. We performed short term LVAD (CentriMag; Thoratec) implantation via median sternotomy with percutaneous cannulas. Patients were included regardless of perioperative status and severity of heart failure. Patients suffering postcardiotomy cardiogenic shock, receiving isolated RVAD as well as posttransplant patients were excluded from this study. RESULTS: Mean duration of support in the survivor group was 35 +/- 25 days versus 25 +/- 25 days in the nonsurvivor group (n.s.), range from 1 to 109 days. The overall survival on support was 40 (60%) patients. In the survivor group 12 patients could be successfully weaned from the system, 12 patients received a heart transplant and in 16 a long-term VAD was implanted. In the nonsurvivor group the rate of preoperative extracorporeal life support, the rate of postoperative renal failure and multiorgan failure was significantly higher. CONCLUSIONS: Thanks to its capacity for full ventricular support, short term univentricular or biventricular LevotronixCentriMag VAD currently represents an ideal solution for bridge-to-decision. PMID- 27184947 TI - Psychiatric and Behavioural Disorders in Children with Epilepsy (ILAE Task Force Report): Behavioural effects of epilepsy surgery. AB - There are relatively few studies of the behavioural outcome of epilepsy surgery in children that have used standardised behavioural measures before and after the procedure. Those investigations that have used such measures are often on mixed groups with mixed pathology, implying that the numbers, when stratified, are very small. They are also often retrospective. Furthermore, because placebo surgery is generally not an option, the studies have been open and they are usually uncontrolled. The few available data suggest that, although individual children may benefit or deteriorate, there is little overall group effect of temporal or extratemporal surgery on behavioural/psychiatric outcome. Hemispherectomy has traditionally been associated with the expectation of marked behavioural improvement but firm data are lacking. Multiple subpial transection performed for electrical status epilepticus of slow-wave sleep in the Landau-Kleffner syndrome can result in marked improvements in cognition and behaviour. Vagus nerve stimulation appears to improve quality of life and mood/behaviour but again the quality of the data has been questioned. There is a need for large, prospective, multicentre, collaborative studies using standardised cognitive and behavioural measures before and after surgery to provide an adequate database on the outcome of various categories of procedures, pathologies and patients. PMID- 27184946 TI - The neurological, neuroimaging and neuropsychological effects of playing professional football: Results of the UK five-year follow-up study. AB - BACKGROUND: Whilst the scientific understanding of mild traumatic brain injury sequelae has advanced, the consequences of neurological insults sustained during football play in the form of multiple concussions and heading remains unclear. METHOD: To the authors' knowledge, this is the first longitudinal prospective study to follow-up a group of footballers and controls over time. Thirty-two elite young professional footballers were recruited and 24 were identified at follow-up. Thirty-three controls were recruited and 17 identified at follow-up. Medical examination, MRI (brain) imaging and detailed neuropsychological data were collected on the footballers at baseline and 5-year follow-up. Medical examination and detailed neuropsychological data were collected on the controls at baseline and 5-year follow-up. RESULTS: All participants had normal neurological examination at both time points. At baseline, 37% of the footballers had sustained minor neurological insults. Between baseline and 5 years, 66% of the footballers had sustained minor neurological insults. No MRI (brain) abnormalities were identified among the footballers at either time point. Regarding the neuropsychology, there was a 6-point IQ difference between footballers and controls, with the footballers being low. Test-re-test analysis on a range of carefully selected neurocognitive tests revealed a picture of good stability in cognitive functioning over this 5-year period. CONCLUSIONS: These longitudinal prospective data indicate no significant neurological, structural brain imaging or neuropsychological change among a sample of young elite professional footballers over the first 5 years of their professional career. PMID- 27184948 TI - Morphological and behavioral characterization of adult mice deficient for SrGAP3. AB - SrGAP3 belongs to the family of Rho GTPase proteins. These proteins are thought to play essential roles in development and in the plasticity of the nervous system. SrGAP3-deficient mice have recently been created and approximately 10 % of these mice developed a hydrocephalus and died shortly after birth. The others survived into adulthood, but displayed neuroanatomical alteration, including increased ventricular size. We now show that SrGAP3-deficient mice display increased brain weight together with increased hippocampal volume. This increase was accompanied by an increase of the thickness of the stratum oriens of area CA1 as well as of the thickness of the molecular layer of the dentate gyrus (DG). Concerning hippocampal adult neurogenesis, we observed no significant change in the number of proliferating cells. The density of doublecortin-positive cells also did not vary between SrGAP3-deficient mice and controls. By analyzing Golgi impregnated material, we found that, in SrGAP3-deficient mice, the morphology and number of dendritic spines was not altered in the DG. Likewise, a Sholl-analysis revealed no significant changes concerning dendritic complexity as compared to controls. Despite the distinct morphological alterations in the hippocampus, SrGAP3-deficient mice were relatively inconspicuous in their behavior, not only in the open-field, nest building but also in the Morris water-maze. However, the SrGAP3-deficient mice showed little to no interest in burying marbles; a behavior that is seen in some animal models related to autism, supporting the view that SrGAP3 plays a role in neurodevelopmental disorders. PMID- 27184950 TI - Identification and sexually dimorphic expression of vasa isoforms in Dabry's sturgeon (Acipenser dabryanus), and functional analysis of vasa 3'-untranslated region. AB - Germ cells are set aside from somatic cells early in embryogenesis, and are responsible for transmitting genetic information through generations. Vasa is a highly conserved germ cell marker across animal phyla, and widely used to label primordial germ cells. Dabry's sturgeon is a rare and endangered species distributed solely in the Yangtze River basin. Here, seven vasa isoforms, named Advasa1-7, were isolated and characterized in Dabry's sturgeon. RT-PCR and western blot analyses revealed that vasa mRNA and protein were mainly restricted to the testis and ovary, but exhibited sexually dimorphic expression. Cellular and subcellular localization uncovered that Advasa mRNA and protein displayed mitotic and meiotic expression in females, and mainly showed mitotic expression in males; surprisingly, they exhibited both cytoplasmic and nuclear expression in the ovarian germ cells, while showing exclusively cytoplasmic expression in the testicular germ cells. By microinjecting chimeric RNA consisting of the red fluorescent protein coding region and the Advasa 3'-untranslated region into embryos of Dabry's sturgeon, zebrafish and medaka, we demonstrated that it had the ability to visualize primordial germ cells (PGCs) in Dabry's sturgeon and zebrafish but not in medaka. It seemed that the machinery of vasa 3'UTR RNA localization was conserved between Dabry's sturgeon and ostariophysan, while possibly changed during the divergence of euteleosts and ostariophysan. Finally, Dabry's sturgeon PGCs moved on the yolk ball, and migrated toward the genital ridge via mesenchyme. Taken together, these results provide new information for vasa expression pattern and function, and lay a foundation for PGC cryopreservation and conservation of Dabry's sturgeon. PMID- 27184951 TI - A tale of two orgins: do myofibroblasts originate from different sources in wound healing and fibrosis? PMID- 27184949 TI - Small nuclear ribonucleoprotein polypeptide N (Sm51) promotes osteogenic differentiation of bone marrow mesenchymal stem cells by regulating Runx2. AB - Small nuclear ribonucleoprotein-associated polypeptide N mutation in mice is associated with short limbs and lower bone mineral density, yet the role of Sm51 in MSC differentiation to osteoblasts is not known. In the present study, we investigate the role of Sm51 in regulating osteoblastic differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs). Stable overexpression of Sm51 in rat and human BM-MSCs (Sm51-MSCs) significantly enhanced their osteogenic differentiation potential compared to untransfected cells. Under osteogenic induction, Sm51-MSCs had higher alkaline phosphatase (ALP) activity and mineralization ability; the expression of osteogenic genes such as runt-related transcription factor 2 (Runx2), osteocalcin, osteopontin, ALP and type I collagen was significantly upregulated compared to the control BM-MSCs. Furthermore, we show that Sm51 overexpression upregulated Runx2 expression at both the RNA and protein level; Sm51 could bind to Runx2 RNA and regulate its expression. Finally, knocking down Runx2 abolished the promoting effects of Sm51 on osteogenesis in BM MSCs. These results demonstrate that Sm51 plays an important role in regulating osteogenic differentiation of MSCs through increasing Runx2 expression and that Sm51 may be a potential new therapeutic target for promoting bone formation. PMID- 27184952 TI - TNF-alpha Activates High-Mobility Group Box 1 - Toll-Like Receptor 4 Signaling Pathway in Human Aortic Endothelial Cells. AB - BACKGROUND/AIMS: Toll-like receptor 4 (TLR4) interacts with endogenous substances as well as lipopolysaccharide. We explored whether TLR4 is implicated in tumor necrosis factor-alpha (TNF-alpha) signal transduction in human aortic endothelial cells. METHODS: The pathway was evaluated by transfection of siRNAs, immunoprecipitation and Western blot analysis. RESULTS: TNF-alpha activated spleen tyrosine kinase (Syk) within 10 min, which led to endothelin-1 (ET-1) production. TLR4 was also rapidly activated by TNF-alpha stimulation, as shown by recruitment of interleukin-1 receptor-associated kinase 1 to TLR4 and its adaptor molecule, myeloid differentiation factor 88 (MyD88). siRNA depletion of TLR4 markedly attenuated TNF-alpha-induced Syk activation and ET-1 production. TLR4 inhibitor (CLI-095), TLR4-neutralizing antibody and siRNA depletion of MyD88 also attenuated TNF-alpha-induced Syk activation. Syk was co-immunoprecipitated with TLR4, and TNF-alpha activated Syk bound to TLR4. High-mobility group box 1 (HMGB1) was rapidly released and associated with TLR4 after TNF-alpha stimulation with a peak at 5 min, which was prevented by N-acetylcysteine, an antioxidant. Glycyrrhizin (HMGB1 inhibitor), HMGB1-neutralizing antibody and siRNA depletion of HMGB1 all suppressed TNF-alpha-induced Syk activation and ET-1 production. CONCLUSION: Upon TNF-alpha stimulation, TLR4 is activated by HMGB1 that is immediately released after the generation of reactive oxygen species, and plays a crucial role in the signal transduction. PMID- 27184953 TI - Reproducibility of a novel echocardiographic 3D automated software for the assessment of mitral valve anatomy. AB - BACKGROUND: 3D transesophageal echocardiography (TEE) is superior to 2D TEE in quantitative anatomic evaluation of the mitral valve (MV) but it shows limitations regarding automatic quantification. Here, we tested the inter-/intra observer reproducibility of a novel full-automated software in the evaluation of MV anatomy compared to manual 3D assessment. METHODS: Thirty-six out of 61 screened patients referred to our Cardiac Imaging Unit for TEE were retrospectively included. 3D TEE analysis was performed both manually and with the automated software by two independent operators. Mitral annular area, intercommissural distance, anterior leaflet length and posterior leaflet length were assessed. RESULTS: A significant correlation between both methods was found for all variables: intercommissural diameter (r = 0.84, p < 0.01), mitral annular area (r = 0.94, p > 0, 01), anterior leaflet length (r = 0.83, p < 0.01) and posterior leaflet length (r = 0.67, p < 0.01). Interobserver variability assessed by the intraclass correlation coefficient was superior for the automatic software: intercommisural distance 0.997 vs. 0.76; mitral annular area 0.957 vs. 0.858; anterior leaflet length 0.963 vs. 0.734 and posterior leaflet length 0.936 vs. 0.838. Intraobserver variability was good for both methods with a better level of agreement with the automatic software. CONCLUSIONS: The novel 3D automated software is reproducible in MV anatomy assessment. The incorporation of this new tool in clinical MV assessment may improve patient selection and outcomes for MV interventions as well as patient diagnosis and prognosis stratification. Yet, high-quality 3D images are indispensable. PMID- 27184954 TI - Detailed protocol to assess in vivo and ex vivo myeloperoxidase activity in mouse models of vascular inflammation and disease using hydroethidine. AB - Myeloperoxidase (MPO) activity contributes to arterial inflammation, vascular dysfunction and disease, including atherosclerosis. Current assessment of MPO activity in biological systems in vivo utilizes 3-chlorotyrosine (3-Cl-Tyr) as a biomarker of hypochlorous acid (HOCl) and other chlorinating species. However, 3 Cl-Tyr is formed in low yield and is subject to further metabolism. Recently, we reported a method to selectively assess MPO-activity in vivo by measuring the conversion of hydroethidine to 2-chloroethidium (2-Cl-E(+)) by liquid chromatography with tandem mass spectrometry (LC-MS/MS) (J. Biol. Chem., 289, 2014, pp. 5580-5595). The hydroethidine-based method has greater sensitivity for MPO activity than measurement of 3-Cl-Tyr. The current methods paper provides a detailed protocol to determine in vivo and ex vivo MPO activity in arteries from mouse models of vascular inflammation and disease by utilizing the conversion of hydroethidine to 2-Cl-E(+). Procedures for the synthesis of standards, preparation of tissue homogenates and the generation of 2-Cl-E(+) are also provided in detail, as are the conditions for LC-MS/MS detection of 2-Cl-E(+). PMID- 27184956 TI - GSH-targeted nanosponges increase doxorubicin-induced toxicity "in vitro" and "in vivo" in cancer cells with high antioxidant defenses. AB - Several reports indicate that chemo-resistant cancer cells become highly adapted to intrinsic oxidative stress by up-regulating their antioxidant systems, which causes an increase of intracellular GSH content. Doxorubicin is one of the most widely used drugs for tumor treatment, able to kill cancer cells through several mechanisms. However, doxorubicin use is limited by its toxicity and cancer resistance. Therefore, new therapeutic strategies able to reduce doses and to overcome chemo-resistance are needed. A new class of glutathione-responsive cyclodextrin nanosponges (GSH-NS), is able to release anticancer drugs preferentially in cells having high GSH content. Doxorubicin-loaded GSH-NS, in the cancer cells with high GSH content, inhibited clonogenic growth, cell viability, topoisomerase II activity and induced DNA damage with higher effectiveness than free drug. Moreover, GSH-NS reduced the development of human tumor in xenograft models more than free drug. These characteristics indicate that GSH-NS can be a suitable drug delivery carrier for future applications in cancer therapy. PMID- 27184958 TI - Taking the RISC of exiting naive pluripotency. AB - A new study shows how RNA-induced silencing complex (RISC)-mediated posttranscriptional regulation of chromatin remodelers allows for tight control of the naive-to-primed pluripotency transition. PMID- 27184955 TI - Regulation of NADPH oxidases in skeletal muscle. AB - The only known function of NAD(P)H oxidases is to produce reactive oxygen species (ROS). Skeletal muscles express three isoforms of NAD(P)H oxidases (Nox1, Nox2, and Nox4) that have been identified as critical modulators of redox homeostasis. Nox2 acts as the main source of skeletal muscle ROS during contractions, participates in insulin signaling and glucose transport, and mediates the myocyte response to osmotic stress. Nox2 and Nox4 contribute to skeletal muscle abnormalities elicited by angiotensin II, muscular dystrophy, heart failure, and high fat diet. Our review addresses the expression and regulation of NAD(P)H oxidases with emphasis on aspects that are relevant to skeletal muscle. We also summarize: i) the most widely used NAD(P)H oxidases activity assays and inhibitors, and ii) studies that have defined Nox enzymes as protagonists of skeletal muscle redox homeostasis in a variety of health and disease conditions. PMID- 27184959 TI - Socioeconomic differences in one-year survival after ischemic stroke: the effect of acute and post-acute care-pathways in a cohort study. AB - BACKGROUND: The reasons for socioeconomic inequity in stroke mortality are not well understood. The aim of this study was to explore the role of ischemic stroke care-pathways on the association between education level and one-year survival after hospital admission. METHODS: Hospitalizations for ischemic stroke during 2011/12 were selected from Lazio health data. Patients' clinical history was defined by retrieving previous hospitalizations and drugs prescriptions. The association between education level and mortality after stroke was studied for acute and post-acute phases using multilevel logistic models (Odds Ratio (OR)). Different scenarios of quality care-pathways were identified considering hospital performance, access to rehabilitation and drug treatment post-discharge. The probability to survive to acute and post-acute phases according to education level and care-pathway scenarios was estimated for a "mean-severity" patient. One year survival probability was calculated as the product of two probabilities. For each scenario, the 1-year survival probability ratio, university versus elementary education, and its Bootstrap Confidence Intervals (95 % BCI) were calculated. RESULTS: We identified 9,958 patients with ischemic stroke, 53.3 % with elementary education level and 3.2 % with university. The mortality was 14.9 % in acute phase and 14.3 % in post-acute phase among survived to the acute phase. The adjusted mortality in acute and post-acute phases decreased with an increase in educational level (OR = 0.90 p-trend < 0.001; OR = 0.85 p-trend < 0.001). For the best care-pathway, the one-year survival probability ratio was 1.06 (95 % BCI = 1.03-1.10), while it was 1.17 (95 % BCI = 1.09-1.25) for the worst. CONCLUSIONS: Education level was inversely associated with mortality both in acute and post-acute phases. The care-pathway reduces but does not eliminate 1 year survival inequity. PMID- 27184957 TI - Redox regulation of autophagy in skeletal muscle. AB - Autophagy is a cellular degradative pathway that involves the delivery of cytoplasmic components, including proteins and organelles, to the lysosome for degradation. Autophagy is implicated in the maintenance of skeletal muscle; increased autophagy leads to muscle atrophy while decreased autophagy leads to degeneration and weakness. A growing body of work suggests that reactive oxygen species (ROS) are important cellular signal transducers controlling autophagy. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and mitochondria are major sources of ROS generation in skeletal muscle that are likely regulating autophagy through different signaling cascades based on localization of the ROS signals. This review aims to provide insight into the redox control of autophagy in skeletal muscle. Understanding the mechanisms by which ROS regulate autophagy will provide novel therapeutic targets for skeletal muscle diseases. PMID- 27184960 TI - Ultrastiff and Strong Graphene Fibers via Full-Scale Synergetic Defect Engineering. AB - Kilometer-scale continuous graphene fibers (GFs) with outstanding mechanical properties and excellent electrical conductivity are produced by high-throughput wet-spinning of graphene oxide liquid crystals followed by graphitization through a full-scale synergetic defect-engineering strategy. GFs with superior performances promise wide applications in functional textiles, lightweight motors, microelectronic devices, and so on. PMID- 27184961 TI - Erratum to: Pain management strategies for neuropathic pain in Fabry disease - a systematic review. PMID- 27184962 TI - Provision of dementia-related services in Canada: a comparative study. AB - BACKGROUND: Dementia is common, particularly among older adults, and is one of the major causes of dependency later in life. We sought to provide an overview and comparison of key services related to dementia care as the disease progresses in three large Canadian healthcare centres. METHODS: We identified family physicians, geriatric specialists, and dementia case managers from three major population centres in Canada with universal healthcare coverage. Using a standardized longitudinal dementia case vignette, participants were interviewed on services they would provide at each stage of the disease. We used principles of content analysis to generate codes and identify themes; appropriate time frames from the vignette fitting the necessary provision of services were derived from the Canadian consensus statement and determined in consultation with clinical experts. Proportions of participants that identified dementia-related care services were analyzed at each time point of the vignette using chi-square tests. RESULTS: Thirty-four healthcare providers from Calgary (Alberta), Edmonton (Alberta), and Ottawa (Ontario) participated. Review of our data identified seven overarching themes of dementia-related care services. Services provided in the community setting include future planning and related services, educational and social support services, and home care and respite services. Although all providers consistently identified educational and social support services (e.g. the Alzheimer Society) within the appropriate time frame, the provision of other services was variable. The proportion of providers reporting potential access of future planning services was significantly different across the three sites (Calgary, 91.7 %; Edmonton; 58.3 %; and Ottawa, 30.0 %), p = 0.012. Also, the proportion of providers that identified day program services were significantly different across the three sites (Calgary, 100.0 %; Edmonton, 91.7 %; and Ottawa, 60.0 %), p = 0.023 according to a chi-square test. CONCLUSIONS: We found important types of variability in service delivery among different regions in Canada for a typical patient with dementia and their family caregiver. Health systems can be calibrated by aligning services from different settings to appropriate time points in the vignette, which illustrates the dynamic course of service delivery and opportunities for improvement throughout the disease trajectory. PMID- 27184964 TI - Theoretical Calculations of Refractive Properties for Hg3Te2Cl2 Crystals. AB - This paper reviews the optical properties, such as refractive index, optical dielectric constant, and reflection coefficient of the Hg3Te2Cl2 crystals. The applications of the Hg3X2Y2 crystals as electronic, optical, and optoelectronic devices are very much determined by the nature and magnitude of these fundamental material properties. The origin of chemical bonding in the crystals is very important for definition of the physical and chemical properties. The main structural feature of the Hg3X2Y2 crystals is the presence of covalent pyramids [XHg3] and linear X-Hg-X groups. Optical properties are calculated according to the model proposed by Harrison. The refractive index in the spectral region far from the absorption edge is determined within the generalized single-oscillator model. The calculated results are found to be in good agreement with experimental data. PMID- 27184963 TI - Characterizing implementation strategies using a systems engineering survey and interview tool: a comparison across 10 prevention programs for drug abuse and HIV sexual risk behavior. AB - BACKGROUND: Although many behavioral interventions have proven to be efficacious, new methodologies are required beyond efficacy trials to understand how to adopt, implement with fidelity, and sustain behavioral interventions in community settings. In this paper, we present a new approach, based on systems engineering concepts and methods, for characterizing implementation strategies that are used to deliver evidence-based behavioral interventions in health and social service settings. We demonstrate the use of this approach with implementation strategies, used or being used for broader dissemination of 10 evidence-based prevention program projects focused on the prevention of drug or HIV sex risk behaviors. RESULTS: The results indicate that there are wide variations in intervention approaches and that there are challenges in program implementation including maintaining program fidelity, serving community needs, and adequate resources. The results also indicate that implementation requires a committed partnership between the program developers, implementation researchers, and community partners. In addition, there is a need for adaptability within programs to meet community needs, resources, and priorities while maintaining program fidelity. CONCLUSIONS: Our methodological approach enabled us to highlight challenges associated with the community implementation of health risk prevention interventions. We also demonstrate how comprehensive descriptions of interventions facilitate understanding of the requirements of program implementation and decisions about the feasibility of implementing a program in community settings. PMID- 27184965 TI - The Peculiarities of Strain Relaxation in GaN/AlN Superlattices Grown on Vicinal GaN (0001) Substrate: Comparative XRD and AFM Study. AB - Superlattices (SLs) consisting of symmetric layers of GaN and AlN have been investigated. Detailed X-ray diffraction and reflectivity measurements demonstrate that the relaxation of built-up strain in the films generally increases with an increasing number of repetitions; however, an apparent relaxation for subcritical thickness SLs is explained through the accumulation of Nagai tilt at each interface of the SL. Additional atomic force microscopy measurements reveal surface pit densities which appear to correlate with the amount of residual strain in the films along with the appearance of cracks for SLs which have exceeded the critical thickness for plastic relaxation. These results indicate a total SL thickness beyond which growth may be limited for the formation of high-quality coherent crystal structures; however, they may indicate a growth window for the reduction of threading dislocations by controlled relaxation of the epilayers. PMID- 27184966 TI - Electrical and Optical Properties of CeNi5 Nanoscale Films. AB - Rare earth compounds are interesting from both a theoretical point of view and for their applications. That is the reason why determining their optical and electrical properties deserves special attention. In this article, we present the conditions we obtained homogenous CeNi5 thin films of nanometer thicknesses. To achieve this goal, our method of choice was laser-induced vaporization, using short and modulated impulses, with electro-optical tuning for the quality factor. The layers that were deposited at a single laser burst had thicknesses between 1.5 and 2.5 nm, depending on the geometry of the experimental setup.Structural and compositional studies of the nanoscale films were made using XRD. The temperature dependence of electrical conductivity was also determined. The following optical properties of the specimens were computed using the Kramers Kronig framework and discussed: absolute reflection and transmission coefficients for a single wavelength and relative ones for the wide UV-VIS-IR spectra, spectral dependence of the refractive index, and extinction coefficient as real and imaginary parts of the complex refractive index. The valence band studies were made with X-ray photoelectron spectroscopy. All these determinations were well correlated and permitted the evaluation of the energy densities of states in the deeper bands, near the Fermi energy, and at the surface states. PMID- 27184967 TI - The defective expression of gtpbp3 related to tRNA modification alters the mitochondrial function and development of zebrafish. AB - Human mitochondrial DNA (mtDNA) mutations have been associated with a wide spectrum of clinical abnormalities. However, nuclear modifier gene(s) modulate the phenotypic expression of pathogenic mtDNA mutations. In our previous investigation, we identified the human GTPBP3 related to mitochondrial tRNA modification, acting as a modifier to influence of deafness-associated mtDNA mutation. Mutations in GTPBP3 have been found to be associated with other human diseases. However, the pathophysiology of GTPBP3-associated disorders is still not fully understood. Here, we reported the generation and characterization of Gtpbp3 depletion zebrafish model using antisense morpholinos. Zebrafish gtpbp3 has three isoforms localized at mitochondria. Zebrafish gtpbp3 is expressed at various embryonic stages and in multiple tissues. In particular, the gtpbp3 was expressed more abundantly in adult zebrafish ovary and testis. The expression of zebrafish gtpbp3 can functionally restore the growth defects caused by the mss1/gtpbp3 mutation in yeast. A marked decrease of mitochondrial ATP generation accompanied by increased levels of apoptosis and reactive oxygen species were observed in gtpbp3 knockdown zebrafish embryos. The Gtpbp3 morphants exhibited defective in embryonic development including bleeding, melenin, oedema and curved tails within 5days post fertilization, as compared with uninjected controls. The co-injection of wild type gtpbp3 mRNA partially rescued these defects in Gtpbp3 morphants. These data suggest that zebrafish Gtpbp3 is a structural and functional homolog of human and yeast GTPBP3. The mitochondrial dysfunction caused by defective Gtpbp3 may alter the embryonic development in the zebrafish. In addition, this zebrafish model of mitochondrial disease may provide unique opportunities for studying defective tRNA modification, mitochondrial biogenesis, and pathophysiology of mitochondrial disorders. PMID- 27184969 TI - Ascitic Calprotectin is a Novel and Accurate Marker for Spontaneous Bacterial Peritonitis. AB - BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a known complication of advanced cirrhosis and presents a high mortality rate. A polymorphonuclear (PMN) cell count >250/MUl in the ascitic fluid is the current gold standard for diagnosing SBP. AIM: We evaluated the accuracy of a point-of-care test (POCT) for ascitic calprotectin in diagnosing patients with SBP. METHODS: Eighty-eight patients admitted with decompensation of liver cirrhosis were studied including 41 patients (46.6%) with SBP. Ascitic calprotectin was measured using a quantitative POCT developed by Buhlmann(r) . RESULTS: Calprotectin levels correlated with PMN cell count and other inflammatory markers and were significantly higher in patients with SBP. An optimal cutoff of calprotectin above 1.57 MUg/ml presented high sensitivity (87.8%), specificity (97.9%), and positive (97.3%) and negative (90.2%) predictive values for diagnosing SBP. Using calprotectin selectively in patients with a serum albumin-ascites gradient above 11 g/l further increased the sensitivity and negative predictive values of the test. CONCLUSION: Ascitic calprotectin appears to be a reliable method for diagnosing SBP in patients with liver cirrhosis. It may present an alternative to other conventional diagnostic methods. PMID- 27184968 TI - Double-Network Hydrogels Strongly Bondable to Bones by Spontaneous Osteogenesis Penetration. AB - On implanting hydroxyapatite-mineralized tough hydrogel into osteochondral defects of rabbits, osteogenesis spontaneously penetrates into the gel matrix owing to the semi-permeablility of the hydrogel. The gradient layer (around 40 MUm thick) contributes quite strong bonding of the gel to bone. This is the first success in realizing the robust osteointegration of tough hydrogels, and the method is simple and feasible for practical use. PMID- 27184972 TI - Description of Aspergillus flavus growth under the influence of different factors (water activity, incubation temperature, protein and fat concentration, pH, and cinnamon essential oil concentration) by kinetic, probability of growth, and time to-detection models. AB - A Box-Behnken design was used to determine the effect of protein concentration (0, 5, or 10g of casein/100g), fat (0, 3, or 6g of corn oil/100g), aw (0.900, 0.945, or 0.990), pH (3.5, 5.0, or 6.5), concentration of cinnamon essential oil (CEO, 0, 200, or 400MUL/kg) and incubation temperature (15, 25, or 35 degrees C) on the growth of Aspergillus flavus during 50days of incubation. Mold response under the evaluated conditions was modeled by the modified Gompertz equation, logistic regression, and time-to-detection model. The obtained polynomial regression models allow the significant coefficients (p<0.05) for linear, quadratic and interaction effects for the Gompertz equation's parameters to be identified, which adequately described (R2>0.967) the studied mold responses. After 50days of incubation, every tested model system was classified according to the observed response as 1 (growth) or 0 (no growth), then a binary logistic regression was utilized to model A. flavus growth interface, allowing to predict the probability of mold growth under selected combinations of tested factors. The time-to-detection model was utilized to estimate the time at which A. flavus visible growth begins. Water activity, temperature, and CEO concentration were the most important factors affecting fungal growth. It was observed that there is a range of possible combinations that may induce growth, such that incubation conditions and the amount of essential oil necessary for fungal growth inhibition strongly depend on protein and fat concentrations as well as on the pH of studied model systems. The probabilistic model and the time-to-detection models constitute another option to determine appropriate storage/processing conditions and accurately predict the probability and/or the time at which A. flavus growth occurs. PMID- 27184970 TI - Adolescents' Attitudes on Smoking Are Related to Experimentation with Smoking, Daily Smoking and Best Friends' Smoking in Two Karelias in Finland and in Russia. AB - PURPOSE: Becoming a smoker usually starts during adolescence and is a dynamic process involving experimentation before the establishment of daily smoking. It has been suggested that adolescents who smoke differ from those who do not in their attitudes to smoking. The purpose of this study was to find out whether attitudes related to smoking legislation and restrictions, social pressures in smoking and image of smokers are associated with smoking experimentation, daily smoking and best friends' smoking. METHOD: The data were gathered with a self administered questionnaire in North Karelia, Eastern Finland and in the Pitkyaranta district, Republic of Karelia, Russia. The respondents were 15-year old 9th grade pupils in local schools. In Pitkyaranta, the data analyses covered pupils in all eight schools in the area (n = 179). In North Karelia, the data analyses comprised of selected eight schools (n = 601). Data were analysed with exploratory factor analysis. RESULTS: The models revealed that attitudes related to restrictions and social pressure were significantly associated with experimenting with smoking [OR (95 % CI) 7.923 (5.787-10.847)], daily smoking [OR (95 % CI) 9.575 (6.727-13.628)] and the likelihood of best friends' smoking [OR (95 % CI) 3.154 (2.579-3.858)]. The stronger the young peoples' attitudes and opinions, for example, towards restrictions and with more difficulties in refusing smoking, the higher the likelihood for smoking experimentations, daily smoking as well as the likelihood for their best friends' smoking. The country and factor interactions were not associated with smoking experimentations, daily smoking or best friends' smoking. CONCLUSION: Regardless of cultural background, adolescents who smoke have more positive attitudes to smoking, and perceive more social support for smoking, than do adolescents who do not smoke. The study stresses the similarity of the results in both Karelia's despite the enormous differences in culture, economy and public policy. PMID- 27184973 TI - A method to isolate bacterial communities and characterize ecosystems from food products: Validation and utilization in as a reproducible chicken meat model. AB - Influenced by production and storage processes and by seasonal changes the diversity of meat products microbiota can be very variable. Because microbiotas influence meat quality and safety, characterizing and understanding their dynamics during processing and storage is important for proposing innovative and efficient storage conditions. Challenge tests are usually performed using meat from the same batch, inoculated at high levels with one or few strains. Such experiments do not reflect the true microbial situation, and the global ecosystem is not taken into account. Our purpose was to constitute live stocks of chicken meat microbiotas to create standard and reproducible ecosystems. We searched for the best method to collect contaminating bacterial communities from chicken cuts to store as frozen aliquots. We tested several methods to extract DNA of these stored communities for subsequent PCR amplification. We determined the best moment to collect bacteria in sufficient amounts during the product shelf life. Results showed that the rinsing method associated to the use of Mobio DNA extraction kit was the most reliable method to collect bacteria and obtain DNA for subsequent PCR amplification. Then, 23 different chicken meat microbiotas were collected using this procedure. Microbiota aliquots were stored at -80 degrees C without important loss of viability. Their characterization by cultural methods confirmed the large variability (richness and abundance) of bacterial communities present on chicken cuts. Four of these bacterial communities were used to estimate their ability to regrow on meat matrices. Challenge tests performed on sterile matrices showed that these microbiotas were successfully inoculated and could overgrow the natural microbiota of chicken meat. They can therefore be used for performing reproducible challenge tests mimicking a true meat ecosystem and enabling the possibility to test the influence of various processing or storage conditions on complex meat matrices. PMID- 27184971 TI - Hepatitis E virus: Current epidemiology and vaccine. AB - Hepatitis E virus infections have been continuously reported in Indian subcontinent, Africa, southeast and central Asia, posing great health threats to the public, especially to pregnant women. Hecolin(r) is the only licensed HEV vaccine developed by Xiamen Innovax Biotech Co., Ltd. Extensive characterizations on antigenicity, physicochemical properties, efficacy in clinical trials, and manufacturing capability have made Hecolin(r) a promising vaccine for HEV control. However, there are many obstacles in large scale application of Hecolin(r). Efforts are needed to further evaluate safety and efficacy in HEV risk populations, and to complement HEV standards for quality control. Passing World Health Organization prequalification and licensing outside China are priorities as these are also hindering Hecolin(r) promotion. Multilateral cooperation among Chinese vaccine manufacturers, Chinese National Regulatory Authorization (NRA) and WHO will expedite the entrance of Hecolin(r) into international market, so that Hecolin(r) could play its due role in global hepatitis E control. PMID- 27184974 TI - Mechanoluminescence Study of Europium Doped CaZrO3 Phosphor. AB - Behaviour displayed by mechanoluminescence (ML) in CaZrO3:Eu(3+) doped phosphors with variable concentration of europium ions are described. When the ML is excited impulsively by the impact of a load on the phosphors the ML intensity increases with time, attains a maximum value and then it decreases. In the ML intensity versus time curve, the peak increases and shifts towards shorter time values with increasing impact velocities. Sample was synthesized by combustion synthesis method with variable concentration of Eu(3+) ions (0.1, 0.2, 0.5, 1, 1.5 mol%) and characterized by X-ray diffraction technique. The total ML intensity IT is defined as the area below the ML intensity versus time curve. Initially IT increases with impact velocity V0 of the load and then it attains a saturation value for higher values of impact velocities which follow the relation IT = IT (0) exp.(-Vc/V0) where IT (0) and Vc are constants. Total ML intensity increases linearly with the mass of the phosphors for higher impact velocities. The ML intensity Im, corresponding to the peak of ML intensity versus time curve increases linearly with the impact velocities. The time tm, is found to be linearly related to 1000/V0. The mechanoluminescence induced by impulsive excitation in europium doped CaZrO3 phosphors plays a significance role in the understanding of biological sensors and display device application. PMID- 27184977 TI - Enhanced Performance Separations: Smaller, Faster, More Complex Samples. PMID- 27184978 TI - Enhanced stability of Cu(2+)-ATCUN complexes under physiologically relevant conditions by insertion of structurally bulky and hydrophobic amino acid residues into the ATCUN motif. AB - Copper complexes formed by an amino terminal Cu(2+)- and Ni(2+)-binding (ATCUN) motif have attracted attention as metallodrug candidates that cleave DNA or RNA and inactivate enzymes. Although the stability of the Cu(2+)-ATCUN complex under physiologically relevant conditions is a key factor for medical applications, it has remained unclear. Here we prepared a series of ATCUN peptides by inserting various amino acid residues into positions 1 and 2, and investigated the stability of the Cu(2+)-ATCUN complexes in aqueous solution, blood plasma, and living animals. Systematic pH titration showed that the low basicity of the N terminal amine of the peptide stabilized the Cu(2+)-ATCUN complex in aqueous solution. Interestingly, the stability of (64)Cu-labeled ATCUN complexes in blood plasma was significantly enhanced by the structural bulkiness and hydrophobicity of the amino acid residues at positions 1 and 2. To validate the in vivo stability, six ATCUN motifs (YYH, VVH, NNH, TTH, GGH, and DDH) were conjugated to a tumor-targeting peptide, octreotide (Oct). The stability of the (64)Cu-ATCUN Oct complexes in blood plasma showed a similar trend to that of the (64)Cu-ATCUN complexes. The (64)Cu-YYH-Oct complex exhibited the highest stability in blood plasma. According to the positron emission tomography and competitive blocking studies of a tumor-bearing mouse model, (64)Cu-YYH-Oct specifically accumulated in tumors, suggesting that the complex was sufficiently stable to reach its target in vivo. The results show that the structural bulkiness and hydrophobicity of the residues at positions 1 and 2 are key parameters for designing metallodrugs on the basis of the Cu(2+)-ATCUN complex. PMID- 27184975 TI - Metabolically healthy obesity and health-related quality of life: A prospective cohort study. AB - BACKGROUND: Metabolically healthy obesity (MHO) has been associated with lower risk of diabetes than obesity with cardiometabolic abnormalities (CA). However, the effect of MHO on other health outcomes is unknown. OBJECTIVE: To examine the association of metabolic status across categories of body mass index (BMI) with health-related quality of life (HRQL). METHODS: Prospective cohort with 4397 individuals aged >=18 years, recruited in 2008-2010 and followed-up to 2012 in Spain. Normal weight was defined as BMI <25, overweight as BMI 25-29.9, and obesity as BMI >=30 kg/m2. Two metabolic statuses were defined: healthy (0-1 CA) and unhealthy (>=2 CA). HRQL was measured with the physical component summary (PCS) and the mental component summary (MCS) of the SF-12 questionnaire. The association of joint categories of BMI and metabolic status at baseline with HRQL at 2012 was examined using linear regression, and adjusted for the main confounders. RESULTS: Compared to healthy normal-weight subjects, the unhealthy normal-weight and the healthy overweight individuals had a similar PCS score; however, the PCS was lower (worse) among those with unhealthy overweight (-1.79; 95% confidence interval [CI]: -2.66 to -0.94), with MHO (-1.45; 95% CI: -2.67 to 0.24) and unhealthy obesity (-1.97; 95% CI: -2.88 to -1.05). Being overweight or obese was not associated with the MCS score regardless of metabolic status. CONCLUSION: Metabolically unhealthy overweight, as well as obesity regardless of metabolic status, showed a worse physical HRQL. These results suggest that both obesity and CA should be addressed to improve HRQL. PMID- 27184986 TI - Simultaneous Liver-Kidney Allocation: Let's Not Make Perfect the Enemy of Good. PMID- 27184979 TI - CRISPRDetect: A flexible algorithm to define CRISPR arrays. AB - BACKGROUND: CRISPR (clustered regularly interspaced short palindromic repeats) RNAs provide the specificity for noncoding RNA-guided adaptive immune defence systems in prokaryotes. CRISPR arrays consist of repeat sequences separated by specific spacer sequences. CRISPR arrays have previously been identified in a large proportion of prokaryotic genomes. However, currently available detection algorithms do not utilise recently discovered features regarding CRISPR loci. RESULTS: We have developed a new approach to automatically detect, predict and interactively refine CRISPR arrays. It is available as a web program and command line from bioanalysis.otago.ac.nz/CRISPRDetect. CRISPRDetect discovers putative arrays, extends the array by detecting additional variant repeats, corrects the direction of arrays, refines the repeat/spacer boundaries, and annotates different types of sequence variations (e.g. insertion/deletion) in near identical repeats. Due to these features, CRISPRDetect has significant advantages when compared to existing identification tools. As well as further support for small medium and large repeats, CRISPRDetect identified a class of arrays with 'extra-large' repeats in bacteria (repeats 44-50 nt). The CRISPRDetect output is integrated with other analysis tools. Notably, the predicted spacers can be directly utilised by CRISPRTarget to predict targets. CONCLUSION: CRISPRDetect enables more accurate detection of arrays and spacers and its gff output is suitable for inclusion in genome annotation pipelines and visualisation. It has been used to analyse all complete bacterial and archaeal reference genomes. PMID- 27184987 TI - Bioaccumulation and translocation of heavy metals by nine native plant species grown at a sewage sludge dump site. AB - In the present study, nine native plant species were collected to determine their potential to clean up nine heavy metals from soil of a sewage sludge dump site. Almost all nine plant species grown at sewage sludge dump site showed multifold higher concentrations of heavy metals as compared to plants grown at the reference site. All the investigated species were characterized by a bioaccumulation factor (BF) > 1.0 for some heavy metals. BF was generally higher for Cd, followed by Pb, Co, Cr, Cu, Ni, Mn, Zn, and Fe. The translocation factor (TF) varied among plant species, and among heavy metals. For most studied heavy metals, TFs were <1.0. The present study proved that the concentrations of all heavy metals (except Cd, Co, and Pb) in most studied species were positively correlated with those in soil. Such correlations indicate that these species reflect the cumulative effects of environmental pollution from soil, and thereby suggesting their potential use in the biomonitoring of most heavy metals examined. In conclusion, all tissues of nine plant species could act as bioindicators, biomonitors, and remediates of most examined heavy metals. Moreover, Bassia indica, Solanum nigrum, and Pluchea dioscoridis are considered hyperaccumulators of Fe; Amaranthus viridis and Bassia indica are considered hyperaccumulators of Pb; and Portulaca oleracea is considered hyperaccumulator of Mn. PMID- 27184985 TI - Differential contributions of subregions of medial temporal lobe to memory system in amnestic mild cognitive impairment: insights from fMRI study. AB - Altered function of the medial temporal lobe (MTL) is a valuable indicator of conversion from amnestic mild cognitive impairment (aMCI) to Alzheimer's disease. This study is to delineate the functional circuitry of multiple subdivisions of parahippocampal gyrus and hippocampus (HIP) and to examine how this knowledge contributes to a more principled understanding of the contributions of its subregions to memory in aMCI. The functional connectivity (FC) analysis was performed in 85 aMCI and 129 healthy controls. The aMCI demonstrated the distinct disruptive patterns of the MTL subregional connectivity with the whole-brain. The right entorhinal cortex (ERC) and perirhinal cortex (PRC) showed increased connectivity with the left inferior and middle occipital gyrus, respectively, which potentially indicated a compensatory mechanism. Furthermore, the right altered MTL subregional FC was associated with episodic memory performance in aMCI. These results provide novel insights into the heterogeneous nature of its large-scale connectivity in MTL subregions in memory system underlying the memory deficits in aMCI. It further suggests that altered FC of MTL subregions is associated with the impairment of the differential encoding stages of memories and the functional changes in the specific right HIP-ERC-PRC-temporal circuitry may contribute to the impairment of episodic memory in aMCI. PMID- 27184989 TI - What Happens After Health Coaching? Observational Study 1 Year Following a Randomized Controlled Trial. AB - PURPOSE: Health coaching is effective for chronic disease self-management in the primary care safety-net setting, but little is known about the persistence of its benefits. We conducted an observational study evaluating the maintenance of improved cardiovascular risk factors following a health coaching intervention. METHODS: We performed a naturalistic follow-up to the Health Coaching in Primary Care Study, a 12-month randomized controlled trial (RCT) comparing health coaching to usual care for patients with uncontrolled diabetes, hypertension, or hyperlipidemia. Participants were followed up 24 months from RCT baseline. The primary outcome was the proportion at goal for at least 1 measure (hemoglobin A1c, systolic blood pressure, or LDL cholesterol) that had been above goal at enrollment; secondary outcomes included each individual clinical goal. Chi-square tests and paired t-tests compared dichotomous and continuous measures. RESULTS: 290 of 441 participants (65.8%) participated at both 12 and 24 months. The proportion of patients in the coaching arm of the RCT who achieved the primary outcome dropped only slightly from 47.1% at 12 to 45.9% at 24 months (P = .80). The proportion at goal for hemoglobin A1c dropped from 53.4% to 36.2% (P = .03). All other clinical metrics had small, nonsignificant changes between 12 and 24 months. CONCLUSIONS: Results support the conclusion that most improved clinical outcomes persisted 1 year after the completion of the health coaching intervention. PMID- 27184991 TI - Symptomatic and Asymptomatic Colon Cancer Recurrence: A Multicenter Cohort Study. AB - PURPOSE: Follow-up after colorectal cancer treatment with curative intent aims to detect recurrences and metachronous tumors in a timely manner. The objective of this study is to assess how recurrent disease presents and is diagnosed within scheduled follow-up according to the national guideline for the Netherlands. METHODS: In a retrospective study of consecutive patients with colorectal cancer who were treated in 2 hospitals in the Netherlands, we identified patients with colon cancer who underwent surgery with curative intent between January 2007 and December 2012. Patients who developed recurrent disease were included for further analyses. RESULTS: From a total of 446 patients who were been treated for colon carcinoma with curative intent, 74 developed recurrent disease (17%). In 43 of those patients (58%), recurrent disease was detected during a scheduled follow-up visit, with 41 (95%) being asymptomatic. Tumor marker testing, imaging, and colonoscopy identified all of these recurrences. In the remaining 31 patients with recurrent disease (42%), recurrence was found during non-scheduled interval visits; 26 (84%) of these patients were symptomatic. The most prevalent symptoms were abdominal pain, altered defecation, and weight loss. Patients with asymptomatic recurrences had a significantly higher overall survival compared with patients with symptomatic recurrences. CONCLUSIONS: In this cohort, 42% of the recurrences after initial curative treatment for colon cancer were found during non-scheduled interval visits, mainly based on symptoms. Primary care physicians who take care of patients whose colon cancer might recur should be aware of the relatively high rate of symptomatic recurrences and of typical presenting symptoms. PMID- 27184990 TI - Patients' Survival Expectations With and Without Their Chosen Treatment for Prostate Cancer. AB - PURPOSE: Overtreatment of screen-detected localized prostate cancer (LPC) is an important public health concern, since the survival benefit of aggressive treatment (surgery or radiation) has not been well established. We investigated the survival expectations of patients who had LPC with and without their chosen treatment. METHODS: A population-based sample of 260 men (132 black, 128 white) 75 years old or younger with newly diagnosed LPC completed a self-administered survey. How long the patients expected to live with their chosen treatment, how long they would expect to live with no treatment, and factors associated with the difference in perceived life expectancy were assessed using multivariable analysis. RESULTS: Without any treatment, 33% of patients expected that they would live less than 5 years, 41% 5 to 10 years, 21% 10 to 20 years, and 5% more than 20 years. With their chosen treatment, 3% of patients expected to live less than 5 years, 9% 5 to 10 years, 33% 10 to 20 years, and 55% more than 20 years. Treatment chosen, age, general health perception, and perceived cancer seriousness predicted the differences in perceived life expectancy, while race and actual tumor risk did not. After adjustment for other covariates, men who choose surgery or radiation expected greater gain in survival than men who chose watchful waiting or active surveillance. CONCLUSIONS: Most patients with LPC underestimated their life expectancy without treatment and overestimated the gain in life expectancy with surgery or radiation. These unrealistic expectations may compromise patients' ability to make informed treatment decisions and may contribute to overtreatment of LPC. Primary care physicians, when included in the decision process, should focus on helping patients develop realistic expectations and choices that support their treatment goals. PMID- 27184992 TI - Encouraging Patient-Centered Care by Including Quality-of-Life Questions on Pre Encounter Forms. AB - PURPOSE: Patient participation in clinical decision making improves outcomes, including quality of life (QOL), but the typical problem-oriented approach may impede consideration of functional goals. We wondered if patients could encourage primary care physicians to pay attention to their QOL goals by writing them on pre-encounter forms. METHODS: We conducted a randomized controlled trial comparing the impact of 2 different pre-visit questionnaires on the content of patient-physician encounters in a family medicine practice at an academic medical center. Using investigator-blinded block randomization, we arranged for 8 faculty and 8 resident physicians to participate in 2 intervention and 2 control videotaped encounters each for a total of 64 encounters. The intervention questionnaire included questions about QOL goals and concerns, while the control questionnaire asked about symptoms. Videotapes were reviewed to determine whether the patients' QOL goals were mentioned and whether they were used in decision making. We also scored encounters using Modified Flanders Interaction Analysis, which assesses and codifies patient and physician communication, and the Modified Carkhuff-Truax Scale, which measures empathy, attending, congruence, and positive regard. RESULTS: Patients were able to record QOL goals and concerns, but QOL issues were mentioned in only 2 of the 64 encounters, once by a patient and once by a physician. In neither case was this information used in decision making. More empathy was expressed by physicians during control encounters (P = .03). CONCLUSIONS: Patients were able to articulate their QOL goals on paper, but that did not prime them or their physicians to alter the process or content of the clinical encounters. In fact, providing QOL information was associated with reduced physician empathy. PMID- 27184993 TI - Ruling Out Pulmonary Embolism in Primary Care: Comparison of the Diagnostic Performance of "Gestalt" and the Wells Rule. AB - PURPOSE: Diagnostic prediction models such as the Wells rule can be used for safely ruling out pulmonary embolism (PE) when it is suspected. A physician's own probability estimate ("gestalt"), however, is commonly used instead. We evaluated the diagnostic performance of both approaches in primary care. METHODS: Family physicians estimated the probability of PE on a scale of 0% to 100% (gestalt) and calculated the Wells rule score in 598 patients with suspected PE who were thereafter referred to secondary care for definitive testing. We compared the discriminative ability (c statistic) of both approaches. Next, we stratified patients into PE risk categories. For gestalt, a probability of less than 20% plus a negative point-of-care d-dimer test indicated low risk; for the Wells rule, we used a score of 4 or lower plus a negative d-dimer test. We compared sensitivity, specificity, efficiency (percentage of low-risk patients in total cohort), and failure rate (percentage of patients having PE within the low-risk category). RESULTS: With 3 months of follow-up, 73 patients (12%) were confirmed to have venous thromboembolism (a surrogate for PE at baseline). The c statistic was 0.77 (95% CI, 0.70-0.83) for gestalt and 0.80 (95% CI, 0.75-0.86) for the Wells rule. Gestalt missed 2 out of 152 low-risk patients (failure rate = 1.3%; 95% CI, 0.2%-4.7%) with an efficiency of 25% (95% CI, 22%-29%); the Wells rule missed 4 out of 272 low-risk patients (failure rate = 1.5%; 95% CI, 0.4%-3.7%) with an efficiency of 45% (95% CI, 41%-50%). CONCLUSIONS: Combined with d-dimer testing, both gestalt using a cutoff of less than 20% and the Wells rule using a score of 4 or lower are safe for ruling out PE in primary care. The Wells rule is more efficient, however, and PE can be ruled out in a larger proportion of suspected cases. PMID- 27184994 TI - Increasing Rates of Tobacco Treatment Delivery in Primary Care Practice: Evaluation of the Ottawa Model for Smoking Cessation. AB - PURPOSE: We report on the effectiveness of the Ottawa Model for Smoking Cessation (OMSC), a multicomponent knowledge translation intervention, in increasing the rate at which primary care providers delivered smoking cessation interventions using the 3 A's model-Ask, Advise, and Act, and examine clinic-, provider-and patient-level determinants of 3 A's delivery. METHODS: We examined the effect of the knowledge translation intervention in 32 primary care practices in Ontario, Canada, by assessing a cross-sectional sample of patients before the implementation of the OMSC and a second cross-sectional sample following implementation. We used 3-level modeling (clinic, clinician, patient) to examine the main effects and predictors of 3 A's delivery. RESULTS: Four hundred eighty one primary care clinicians and more than 3,500 tobacco users contributed data to the evaluation. Rates of delivery of the 3 A's increased significantly following program implementation (Ask: 55.3% vs 71.3%, P <.001; Advise: 45.5% vs 63.6%, P <.001; Act: 35.4% vs 54.4%, P <.001). The adjusted odds ratios (AOR) for the delivery of 3 A's between the pre- and post-assessments were AOR = 1.94; (95% CI, 1.61-2.34) for Ask, AOR = 1.92; (95% CI, 1.60-2.29) for Advise, and AOR = 2.03; (95% CI, 1.71-2.42) for Act. The quality of program implementation and the reason for clinic visit were associated with increased rates of 3 A's delivery. CONCLUSIONS: Implementation of the OMSC was associated with increased rates of smoking cessation treatment delivery. High quality implementation of the OMSC program was associated with increased rates of 3 A's delivery. PMID- 27184995 TI - Rural Women Family Physicians: Strategies for Successful Work-Life Balance. AB - PURPOSE: Women family physicians experience challenges in maintaining work-life balance while practicing in rural communities. We sought to better understand the personal and professional strategies that enable women in rural family medicine to balance work and personal demands and achieve long-term career satisfaction. METHODS: Women family physicians practicing in rural communities in the United States were interviewed using a semistructured format. Interviews were recorded, professionally transcribed, and analyzed using an immersion and crystallization approach, followed by detailed coding of emergent themes. RESULTS: The 25 participants described a set of strategies that facilitated successful work-life balance. First, they used reduced or flexible work hours to help achieve balance with personal roles. Second, many had supportive relationships with spouses and partners, parents, or other members of the community, which facilitated their ability to be readily available to their patients. Third, participants maintained clear boundaries around their work lives, which helped them to have adequate time for parenting, recreation, and rest. CONCLUSIONS: Women family physicians can build successful careers in rural communities, but supportive employers, relationships, and patient approaches provide a foundation for this success. Educators, employers, communities, and policymakers can adapt their practices to help women family physicians thrive in rural communities. PMID- 27184996 TI - Measuring Patient Safety in Primary Care: The Development and Validation of the "Patient Reported Experiences and Outcomes of Safety in Primary Care" (PREOS-PC). AB - PURPOSE: We set out to develop and validate a patient-reported instrument for measuring experiences and outcomes related to patient safety in primary care. METHOD: The instrument was developed in a multistage process supported by an international expert panel and informed by a systematic review of instruments, a meta-synthesis of qualitative studies, 4 patient focus groups, 18 cognitive interviews, and a pilot study. The trial version of Patient Reported Experiences and Outcomes of Safety in Primary Care (PREOS-PC) covered 5 domains and 11 scales: practice activation (1 scale); patient activation (1 scale); experiences of patient safety events (1 scale); harm (6 scales); and general perceptions of patient safety (2 scales). The questionnaire was posted to 6,736 patients in 45 practices across England. We used "gold standard" psychometric methods to evaluate its acceptability, reliability, structural and construct validity, and ability to discriminate among practices. RESULTS: 1,244 completed questionnaires (18.5%) were returned. Median item-specific response rate was 91.3% (interquartile range 28.0%). No major ceiling or floor effects were observed. All 6 multi-item scales showed high internal consistency (Cronbach's alpha 0.75 0.96). Factor analysis, correlation between scales, and known group analyses generally supported structural and construct validity. The scales demonstrated a heterogeneous ability to discriminate between practices. The final version of PREOS-PC consisted of 5 domains, 8 scales, and 58 items. CONCLUSIONS: PREOS-PC is a new multi-dimensional patient safety instrument for primary care developed with experts and patients. Initial testing shows its potential for use in primary care, and future developments will further address its use in actual clinical practice. PMID- 27184997 TI - Self-Measured vs Professionally Measured Waist Circumference. AB - PURPOSE: Although waist circumference can provide important metabolic risk information, logistic issues inhibit its routine use in outpatient practice settings. We assessed whether self-measured waist circumference is sufficiently accurate to replace professionally measured waist circumference for identifying high-risk patients. METHODS: Medical outpatients and research participants self measured their waist circumference at the same visit during which a professionally measured waist circumference was obtained. Participants were provided with standardized pictorial instructions on how to measure their waist circumference, and professionals underwent standard training. RESULTS: Self- and professionally measured waist circumference data were collected for 585 women (mean +/- SD age = 40 +/- 14 years, mean +/- SD body mass index = 27.7 +/- 6.0 kg/m(2)) and 165 men (mean +/- SD age = 41 +/- 14 years, mean +/- SD body mass index = 29.3 +/- 4.6 kg/m(2)). Although self- and professionally measured waist circumference did not differ significantly, we found a clinically important false negative rate for the self-measurements. Eleven percent of normal-weight and 52% of overweight women had a professionally measured waist circumference putting them in a high-risk category for metabolic syndrome (ie, greater than 88 cm); however, 57% and 18% of these women, respectively, undermeasured their waist circumference as falling below that cutoff. Fifteen percent and 84% of overweight and class I obese men, respectively, had a professionally measured waist circumference putting them in the high-risk category (ie, greater than 102 cm); however, 23% and 16% of these men, respectively, undermeasured their waist circumference as falling below that cutoff. CONCLUSIONS: Despite standardized pictorial instructions for self-measured waist circumference, the false-negative rate of self-measurements approached or exceeded 20% for some groups at high risk for poor health outcomes. PMID- 27184998 TI - Racism in Medicine: Shifting the Power. AB - Medicine has historically been a field where the provider of the service (physician, nurse) has a significant amount of power as compared with the recipient of the service (the patient). For the most part, this power is relatively consistent, and the power dynamic is rarely disrupted. In this essay, I share a personal experience in which a racist rant by a patient seemingly reverses the power dynamic. As the physician, I faced the realization that I may not have as much power as I believed, but fortunately I had some tools that allowed for my resilience. It is my hope that this paper will strengthen other family physicians and professional minorities that are victims of racism, discrimination, and prejudice for their race, sex, ability, sexual orientation, religion, and other axes of discrimination. PMID- 27184999 TI - Sticker Shock: The Experience of a Health Care Consumer. AB - With implementation of the Patient Protection and Affordable Care Act, more Americans are gaining insurance coverage but often have high deductibles and significant out-of-pocket cost sharing. Deductibles routinely exceed $1,000 and often approach $5,000. In this essay, I share our family's experience attempting to navigate urgent medical decisions in a high-deductible health plan. In accessing urgent care for our child's fracture, we unknowingly encountered a 10 fold variation for what should be routine, low-cost technology (ie, plain film x ray). Though the financial consequences for our family were minimal, for many families with high-deductible plans the financial implications are enormous. Through this experience, I learned that the principles of consumer-directed health care-that patients can and should price shop for care-are flawed in urgent and emergent situations. PMID- 27185000 TI - Dad's Last Week. AB - I had intended to spend our spring break week in Montana with my kids and my dad, going to parks and museums together. Instead, I spent the week in the hospital, helping my dad make end-of-life choices and learning more about the importance of communication in health care settings and the preciousness of close relationships in life. I am a better person and a better physician because my dad trusted me to be there while he was dying. During his last week, I was grateful to have spent years studying medicine and years getting to know my dad. This combination of professional and personal knowledge enabled me to help him choose his own end-of life path. As someone who does not like hospitals, I have always wondered why I became a doctor; now I know. PMID- 27185008 TI - Platelets are not hyperreactive in patients with ovarian cancer. AB - Paraneoplastic thrombocytosis has been reported in different types of solid tumors, including ovarian epithelial cancer, and found to be associated with a worse outcome. Although the effect of cancer on increasing platelet counts is well documented, the effect of cancer on platelet functions is not well known. We compared in vitro aggregation response of platelets isolated from 34 patients with ovarian cancer to those of platelets from 19 patients with benign ovarian tumors. Aggregation studies were conducted in a light transmission aggregometer, using both a high and a low dose of ADP and collagen. We evaluated platelet preactivation by measuring the plasma concentration of beta-thromboglobulin (beta TG) and platelet factor-4 (PF-4) as markers of platelet alpha granule secretion, using ELISA. We found that ovarian cancer is not associated with an enhanced aggregation response of platelets to ADP or collagen, and plasma concentration of beta-TG and PF-4 is not higher in patients with ovarian cancer compared to those in patients with benign ovarian tumors. PMID- 27185009 TI - Accidental hypothermia in severe trauma. AB - Hypothermia, along with acidosis and coagulopathy, is part of the lethal triad that worsen the prognosis of severe trauma patients. While accidental hypothermia is easy to identify by a simple measurement, it is no less pernicious if it is not detected or treated in the initial phase of patient care. It is a multifactorial process and is a factor of mortality in severe trauma cases. The consequences of hypothermia are many: it modifies myocardial contractions and may induce arrhythmias; it contributes to trauma-induced coagulopathy; from an immunological point of view, it diminishes inflammatory response and increases the chance of pneumonia in the patient; it inhibits the elimination of anaesthetic drugs and can complicate the calculation of dosing requirements; and it leads to an over-estimation of coagulation factor activities. This review will detail the pathophysiological consequences of hypothermia, as well as the most recent principle recommendations in dealing with it. PMID- 27185011 TI - Expressions of lipoprotein receptors and cholesterol efflux regulatory proteins during luteolysis in bovine corpus luteum. AB - The corpus luteum (CL) synthesises and secretes progesterone (P4), which is essential for the establishment and maintenance of pregnancy in mammals. P4 is synthesised from cholesterol. Cholesterol is internalised by low-density lipoprotein receptor (LDLR) and/or scavenger receptor B1 (SR-BI), and is effluxed by ATP-binding cassette (ABC) transporter A1 (ABCA1) and G1 (ABCG1). To test the hypothesis that lipoprotein receptors and ABC transporters are involved in functional luteolysis, we examined the expression of LDLR, SR-BI, ABCA1 and ABCG1 in bovine CL during the luteal stages and after injection of prostaglandin (PG) F2alpha on Day 10 after ovulation. Expression of LDLR and SR-BI mRNA and protein was lower in the regressed luteal than late luteal stage. Injection of cows with a PGF2alpha did not affect LDLR mRNA and protein levels in the CL. Although expression of SR-BI mRNA did not change, SR-BI protein expression decreased 12 and 24h after PGF2alpha injection. The overall findings of the present study suggest that the decreased expression of SR-BI induced by PGF2alpha is one of the factors responsible for the continuous decrease in P4 production during functional luteolysis. PMID- 27185013 TI - Synthesis and evaluation of raloxifene derivatives as a selective estrogen receptor down-regulator. AB - Estrogen receptors (ERs) play a major role in the growth of human breast cancer cells. A selective estrogen receptor down-regulator (SERD) that acts as not only an inhibitor of ligand binding, but also induces the down-regulation of ER, would be useful for the treatment for ER-positive breast cancer. We previously reported that tamoxifen derivatives, which have a long alkyl chain, had the ability to down-regulate ERalpha. With the aim of expanding range of the currently available SERDs, we designed and synthesized raloxifene derivatives, which had various lengths of the long alkyl chains, and evaluated their SERD activities. All compounds were able to bind ERalpha, and RC10, which has a decyl group on the amine moiety of raloxifene, was shown to be the most potent compound. Our findings suggest that the ligand core was replaceable, and that the alkyl length was important for controlling SERD activity. Moreover, RC10 showed antagonistic activity and its potency was superior to that of 4,4'-(heptane-4,4-diyl)bis(2 methylphenol) (18), a competitive antagonist of ER without SERD activity. These results provide information that will be useful for the development of promising SERDs candidates. PMID- 27185010 TI - Prevention strategies for blood-borne viruses-in the Era of vaccines, direct acting antivirals and antiretroviral therapy. AB - Blood-borne viruses, such as hepatitis B virus, hepatitis C virus, human immunodeficiency virus, and the facultative blood-borne hepatitis E virus, are considered a major public health problem given that they are accountable for millions of deaths each year. Treatment options, including effective vaccine design, development of antiviral strategies and the implementation of antiretroviral therapy have improved substantially over the last couple of years and contribute to successful treatment and prevention of these infectious diseases. In this review, we summarise the current knowledge and concepts in prevention of transmission of these blood-borne viruses. PMID- 27185012 TI - Design, synthesis and biological evaluation of novel tetrahydroisoquinoline quaternary derivatives as peripheral kappa-opioid receptor agonists. AB - A novel series of tetrahydroisoquinoline quaternary derivatives 4 were synthesized as peripheral kappa-opioid receptor agonists. All the target compounds were evaluated in kappa-opioid receptor binding assays, and compounds 4l, 4m, and 4n exhibited high affinity for kappa-opioid receptor. Furthermore, compound 4l (kappaKi=0.94nM) produced potent antinociceptive activity in the mouse acetic acid-induced writhing assay, with lower sedative side effects than the parent compound MB-1c. PMID- 27185015 TI - Cognitive Alexithymia Mediates the Association Between Avoidant Attachment and Interpersonal Problems in Patients With Somatoform Disorder. AB - Patients with somatoform disorder (SFD) are characterized by the presence of chronic physical complaints that are not fully explained by a general medical condition or another mental disorder. Insecure attachment patterns are common in this patient group, which are often associated with interpersonal difficulties. In the present study, the mediational role of two types of alexithymia and negative affectivity (NA) was examined in the association between attachment styles and interpersonal problems in a group of 120 patients with SFD. Patients were requested to fill out several self-report questionnaires for the assessment of attachment strategies, alexithymia, NA, and interpersonal problems. Cognitive alexithymia (i.e., the inability to identify and verbalize emotions) mediated the relationship between avoidant attachment patterns and interpersonal problems, even after controlling for NA. Preliminary findings also suggested that NA acted as a moderator of the mediator cognitive alexithymia. These results have important implications for clinical practice, as this study clearly shows that interpersonal problems do not automatically follow from insecure attachment strategies, but are contingent upon alexithymic features. It is recommended to target alexithymic features in patients with SFD, particularly in the context of negative emotions. Therefore, cognitive alexithymia may be an important therapeutic focus, specifically in the treatment of avoidant ptients with SFD. PMID- 27185016 TI - Corrigendum to ''Language-experience plasticity in neural representation of changes in pitch salience'' [Brain Research 1637 (2016) 102-117]. PMID- 27185014 TI - Antimicrobial Stewardship in Rhode Island Long-Term Care Facilities: Current Standings and Future Opportunities. AB - Our survey of antimicrobial stewardship practices among Rhode Island long-term care facilities demonstrated opportunities to develop formal programs. Results suggest infection preventionists are largely responsible for ensuring appropriate antibiotic use in long-term care facilities and there is a need for increased interdisciplinary access to individuals with antimicrobial stewardship expertise. Infect Control Hosp Epidemiol 2016;37:979-982. PMID- 27185019 TI - [Not Available]. PMID- 27185018 TI - Competing coexisting phases in 2D water. AB - The properties of bulk water come from a delicate balance of interactions on length scales encompassing several orders of magnitudes: i) the Hydrogen Bond (HBond) at the molecular scale and ii) the extension of this HBond network up to the macroscopic level. Here, we address the physics of water when the three dimensional extension of the HBond network is frustrated, so that the water molecules are forced to organize in only two dimensions. We account for the large scale fluctuating HBond network by an analytical mean-field percolation model. This approach provides a coherent interpretation of the different events experimentally (calorimetry, neutron, NMR, near and far infra-red spectroscopies) detected in interfacial water at 160, 220 and 250 K. Starting from an amorphous state of water at low temperature, these transitions are respectively interpreted as the onset of creation of transient low density patches of 4-HBonded molecules at 160 K, the percolation of these domains at 220 K and finally the total invasion of the surface by them at 250 K. The source of this surprising behaviour in 2D is the frustration of the natural bulk tetrahedral local geometry and the underlying very significant increase in entropy of the interfacial water molecules. PMID- 27185017 TI - Renin-angiotensin system inhibitors in patients with coronary artery disease who have undergone percutaneous coronary intervention. AB - The percutaneous coronary intervention (PCI) procedure has become one of the pivotal options in the treatment of coronary artery disease (CAD). Although the PCI procedure has rapidly developed in China, some concerns including in-stent restenosis and dissatisfactory long-term prognosis remain unsolved. Large-scale randomized controlled clinical trials indicate that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) can reduce all cause mortality and recurrent cardiac events in patients with CAD. ACEIs/ARBs are recommended as a fundamental treatment in the secondary prevention of CAD and reduce in-stent restenosis after PCI. This review focuses on the role of ACEIs/ARBs in improving long-term prognosis and reducing in-stent restenosis. PMID- 27185020 TI - Characterization of gene expression profiling of mouse tissues obtained during the postmortem interval. AB - Attempts to establish a tissue bank from autopsy samples have led to uncovering of the secrets of many diseases. Here, we examined the length of time that the RNA from postmortem tissues is available for microarray analysis and reported the gene expression profile for up- and down-regulated genes during the postmortem interval. We extracted RNA from fresh-frozen (FF) and formalin-fixed paraffin embedded (FFPE) brains and livers of three different groups of mice: 1) mice immediately after death, 2) mice that were stored at room temperature for 3h after death, and 3) mice that were stored at 4 degrees C for 18h after death, as this storage resembles the human autopsy process in Japan. The RNA quality of the brain and the liver was maintained up to 18h during the postmortem interval. Based on the microarray analysis, we selected genes that were altered by >1.3 fold or <0.77-fold and classified these genes using hierarchical cluster analysis following DAVID gene ontology analysis. These studies revealed that cytoskeleton related genes were enriched in the set of up-regulated genes, while serine protease inhibitors were enriched in the set of down-regulated genes. Interestingly, although the RNA quality was maintained due to high RNA integrity number (RIN) values, up-regulated genes were not validated by quantitative PCR, suggesting that these genes may become fragmented or modified by an unknown mechanism. Taken together, our findings suggest that under typical autopsy conditions, gene expression profiles that reflect disease pathology can be examined by understanding comprehensive recognition of postmortem fluctuation of gene expression. PMID- 27185021 TI - Burden and happiness in head and neck cancer carers: the role of supportive care needs. AB - PURPOSE: Our study aimed to investigate the relationship between unmet supportive care needs and carer burden and happiness, in head and neck cancer (HNC). METHODS: Two hundred eighty-five HNC informal carers were sent a postal questionnaire between January and June 2014, which included the supportive care needs survey for partners and caregivers of cancer survivors (SCNS-P&C) and the CarerQol, which assesses burden and happiness. Multiple regression analysis was conducted to examine the association of (i) carer characteristics, (ii) carer situation, and (iii) unmet supportive care needs, with carer burden and happiness RESULTS: One hundred ninety-seven carers completed the questionnaire (response rate = 69 %), 180 of whom were included in the analysis. The majority were female (76 %), not in paid employment (68 %) and caring for their spouse (67 %). On average, carers reported relatively low levels of burden and relatively high levels of happiness. Carer factors explained 42 % of variance in levels of burden and 24 % of variance in levels of happiness. Healthcare service needs were associated with carer burden (beta = .28, p = .04), while psychological needs (beta = -.38, p = .028), health care service needs (beta = -.30, p = .049), information needs (beta = .29, p = .028), carer comorbidity (beta = -.18, p = .030), and gender (beta = -.16, p = .045) were associated with happiness. CONCLUSIONS: Our results indicate that different aspects of carer characteristics and unmet needs are associated with carer burden and happiness. Efforts directed at reducing unmet healthcare service needs in particular are merited given their associations with both aspects of carer quality of life. PMID- 27185023 TI - Coronary Computed Tomography Angiography in the Evaluation of Chest Pain of Suspected Cardiac Origin. PMID- 27185026 TI - ECG Response: May 17, 2016. PMID- 27185024 TI - Bulging at the Root: An Inflammatory Tale. PMID- 27185027 TI - One Cause of Secondary Hypertension: Neurogenic Etiology. PMID- 27185022 TI - Brain in Congenital Heart Disease Across the Lifespan: The Cumulative Burden of Injury. AB - The number of patients surviving with congenital heart disease (CHD) has soared over the last 3 decades. Adults constitute the fastest-growing segment of the CHD population, now outnumbering children. Research to date on the heart-brain intersection in this population has been focused largely on neurodevelopmental outcomes in childhood and adolescence. Mutations in genes that are highly expressed in heart and brain may cause cerebral dysgenesis. Together with altered cerebral perfusion in utero, these factors are associated with abnormalities of brain structure and brain immaturity in a significant portion of neonates with critical CHD even before they undergo cardiac surgery. In infancy and childhood, the brain may be affected by risk factors related to heart disease itself or to its interventional treatments. As children with CHD become adults, they increasingly develop heart failure, atrial fibrillation, hypertension, diabetes mellitus, and coronary disease. These acquired cardiovascular comorbidities can be expected to have effects similar to those in the general population on cerebral blood flow, brain volumes, and dementia. In both children and adults, cardiovascular disease may have adverse effects on achievement, executive function, memory, language, social interactions, and quality of life. Against the backdrop of shifting demographics, risk factors for brain injury in the CHD population are cumulative and synergistic. As neurodevelopmental sequelae in children with CHD evolve to cognitive decline or dementia during adulthood, a growing population of CHD can be expected to require support services. We highlight evidence gaps and future research directions. PMID- 27185028 TI - Letter by Aubin et al Regarding Article, "Association of Coffee Consumption with Total and Cause-Specific Mortality in 3 Large Prospective Cohorts". PMID- 27185029 TI - Response to Letter Regarding Article, "Association of Coffee Consumption With Total and Cause-Specific Mortality in 3 Large Prospective Cohorts". PMID- 27185030 TI - Letter by Nikpour et al Regarding Article, "Effect of Warfarin Treatment on Survival of Patients With Pulmonary Arterial Hypertension (PAH) in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL)". PMID- 27185031 TI - Response to Letter Regarding Article, "Effect of Warfarin Treatment on Survival of Patients With Pulmonary Arterial Hypertension (PAH) in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL)". PMID- 27185033 TI - Epidermal grafting versus split-thickness skin grafting for wound healing (EPIGRAAFT): study protocol for a randomised controlled trial. AB - BACKGROUND: Split-thickness skin grafting (SSG) is an important modality for wound closure. However, the donor site becomes a second, often painful wound, which may take more time to heal than the graft site itself and holds the risk of infection and scarring. Epidermal grafting (EG) is an alternative method of autologous skin grafting that harvests only the epidermal layer of the skin by applying continuous negative pressure on the normal skin to raise blisters. This procedure has minimal donor site morbidity and is relatively pain-free, allowing autologous skin grafting in an outpatient setting. We plan to compare EG to SSG and to further investigate the cellular mechanism by which each technique achieves wound healing. METHODS/DESIGN: EPIGRAAFT is a multicentre, randomised, controlled trial that compares the efficacy and wound-healing mechanism of EG with SSG for wound healing. The primary outcome measures are the proportion of wounds healed in 6 weeks and the donor site healing time. The secondary outcome measures include the mean time for complete wound healing, pain score, patient satisfaction, health care utilisation, cost analysis, and incidence of adverse events. DISCUSSION: This study is expected to define the efficacy of EG and promote further understanding of the mechanism of wound healing by EG compared to SSG. The results of this study can be used to inform the current best practise for wound care. TRIAL REGISTRATION: Clinicaltrials.gov identifier, NCT02535481 . Registered on 11 August 2015. PMID- 27185034 TI - Evaluation of suitability of a micro-processing unit of motion analysis for upper limb tracking. AB - The aim of this study is to assess the suitability of a micro-processing unit of motion analysis (MPUMA), for monitoring, reproducing, and tracking upper limb movements. The MPUMA is based on an inertial measurement unit, a 16-bit digital signal controller and a customized algorithm. To validate the performance of the system, simultaneous recordings of the angular trajectory were performed with a video-based motion analysis system. A test of the flexo-extension of the shoulder joint during the active elevation in a complete range of 120o of the upper limb was carried out in 10 healthy volunteers. Additional tests were carried out to assess MPUMA performance during upper limb tracking. The first, a 3D motion reconstruction of three movements of the shoulder joint (flexo-extension, abduction-adduction, horizontal internal-external rotation), and the second, an upper limb tracking online during the execution of three movements of the shoulder joint followed by a continuous random movement without any restrictions by using a virtual model and a mechatronic device of the shoulder joint. Experimental results demonstrated that the MPUMA measured joint angles that are close to those from a motion-capture system with orientation RMS errors less than 3o. PMID- 27185032 TI - BioCode gold-nanobeacon for the detection of fusion transcripts causing chronic myeloid leukemia. AB - BACKGROUND: Gold-nanobeacons (Au-nanobeacons) have proven to be versatile systems for molecular diagnostics and therapeutic actuators. Here, we present the development and characterization of two gold nanobeacons combined with Forster resonance energy transfer (FRET) based spectral codification for dual mode sequence discrimination. This is the combination of two powerful technologies onto a single nanosystem. RESULTS: We proved this concept to detect the most common fusion sequences associated with the development of chronic myeloid leukemia, e13a2 and e14a2. The detection is based on spectral shift of the donor signal to the acceptor, which allows for corroboration of the hybridization event. The Au-nanobeacon acts as scaffold for detection of the target in a homogenous format whose output capability (i.e. additional layer of information) is potentiated via the spectral codification strategy. CONCLUSIONS: The spectral coded Au-nanobeacons permit the detection of each of the pathogenic fusion sequences, with high specificity towards partial complementary sequences. The proposed BioCode Au-nanobeacon concept provides for a nanoplatform for molecular recognition suitable for cancer diagnostics. PMID- 27185035 TI - Parametric electrical impedance tomography for measuring bone mineral density in the pelvis using a computational model. AB - Osteoporosis is defined as bone microstructure deterioration resulting a decrease of bone's strength. Measured bone mineral density (BMD) constitutes the main tool for Osteoporosis diagnosis, management, and defines patient's fracture risk. In the present study, parametric electrical impedance tomography (pEIT) method was examined for monitoring BMD, using a computerized simulation model and preliminary real measurements. A numerical solver was developed to simulate surface potentials measured over a 3D computerized pelvis model. Varying cortical and cancellous BMD were simulated by changing bone conductivity and permittivity. Up to 35% and 16% change was found in the real and imaginary modules of the calculated potential, respectively, while BMD changes from 100% (normal) to 60% (Osteoporosis). Negligible BMD relative error was obtained with SNR>60 [dB]. Position changes errors indicate that for long term monitoring, measurement should be taken at the same geometrical configuration with great accuracy. The numerical simulations were compared to actual measurements that were acquired from a healthy male subject using a five electrodes belt bioimpedance device. The results suggest that pEIT may provide an inexpensive easy to use tool for frequent monitoring BMD in small clinics during pharmacological treatment, as a complementary method to DEXA test. PMID- 27185036 TI - MicroRNA-21 Regulates Non-Small Cell Lung Cancer Cell Invasion and Chemo Sensitivity through SMAD7. AB - BACKGROUND/AIMS: SMAD7 is a key inhibitor of transforming growth factor beta (TGFbeta) receptor signaling, which regulates the alteration of cancer cell invasiveness through epithelial-mesenchymal cell conversion. Carboplatin is a commonly used drug in the chemotherapy for non-small cell lung cancer (NSCLC). Nevertheless, the molecular mechanisms underlying its suppressive effects on the NSCLC cell invasion are not completely understood. In the current study, we addressed this question by analyzing the effects of Carboplatin on microRNA regulated SMAD7. METHODS: We used Carboplatin to treat NSCLC cell lines. We performed bioinformatics analyses on the binding of microRNA-21 (miR-21) to the 3'-UTR of SMAD7 mRNA, and verified the biological effects of this binding using promoter luciferase reporter assay. The effects of Carboplatin or miR-21 modification on NSCLC cell invasion were evaluated in either a transwell cell invasion assay, or a scratch wound healing assay. RESULTS: We found that Carboplatin inhibited the NSCLC cell invasion, in either a transwell cell invasion assay, or a scratch wound healing assay. Moreover, Carboplatin increased the levels of SMAD7 protein, but not mRNA, in NSCLC cells, suggesting presence of post-transcriptional control of SMAD7 by Carboplatin. Furthermore, expression of miR-21 was found to be inhibited by Carboplatin, and bioinformatics analyses showed that miR-21 targeted the 3'-UTR of SMAD7 mRNA to inhibit its translation, which was confirmed by luciferase reporter assay. CONCLUSION: Carboplatin may upregulate SMAD7 through suppression of miR-21 to inhibit TGFbeta receptor signaling mediated NSCLC cell invasion. PMID- 27185037 TI - Prediction of outcome by lymph node ratio in patients with parotid gland cancer. AB - OBJECTIVE: Lymph node ratio (LNR) has been shown to be an independent predictor of recurrence risk and survival in different entities of carcinoma. METHODS: In this retrospective chart review, 128 patients with parotid gland cancer (PGC) subsequently treated by primary surgery were included. About 64% (n = 82) of these patients were additionally treated with adjuvant radiotherapy. Five-year overall survival rates were determined by subgroups based on LNR value. RESULTS: Lymph node ratio was found to be significantly associated with overall survival rate (P < 0.001). Using univariate analyses, pathological tumour-node-metastasis (TNM)-stage, UICC-stage grouping and extracapsular spread were found to be significant predictors of overall survival (P < 0.001). However, with a multivariate analyses, LNR remained the only independent predictor of overall survival (P = 0.043). CONCLUSIONS: After surgery for PGC, evaluation of the neck using LNR was found to reliably stratify the overall survival rate. PMID- 27185039 TI - Moving towards a new vision: implementation of a public health policy intervention. AB - BACKGROUND: Public health systems in Canada have undergone significant policy renewal over the last decade in response to threats to the public's health, such as severe acute respiratory syndrome. There is limited research on how public health policies have been implemented or what has influenced their implementation. This paper explores policy implementation in two exemplar public health programs -chronic disease prevention and sexually-transmitted infection prevention - in Ontario, Canada. It examines public health service providers', managers' and senior managements' perspectives on the process of implementation of the Ontario Public Health Standards 2008 and factors influencing implementation. METHODS: Public health staff from six health units representing rural, remote, large and small urban settings were included. We conducted 21 focus groups and 18 interviews between 2010 (manager and staff focus groups) and 2011 (senior management interviews) involving 133 participants. Research assistants coded transcripts and researchers reviewed these; the research team discussed and resolved discrepancies. To facilitate a breadth of perspectives, several team members helped interpret the findings. An integrated knowledge translation approach was used, reflected by the inclusion of academics as well as decision-makers on the team and as co-authors. RESULTS: Front line service providers often were unaware of the new policies but managers and senior management incorporated them in operational and program planning. Some participants were involved in policy development or provided feedback prior to their launch. Implementation was influenced by many factors that aligned with Greenhalgh and colleagues' empirically-based Diffusion of Innovations in Service Organizations Framework. Factors and related components that were most clearly linked to the OPHS policy implementation were: attributes of the innovation itself; adoption by individuals; diffusion and dissemination; the outer context - interorganizational networks and collaboration; the inner setting - implementation processes and routinization; and, linkage at the design and implementation stage. CONCLUSIONS: Multiple factors influenced public health policy implementation. Results provide empirical support for components of Greenhalgh et al's framework and suggest two additional components - the role of external organizational collaborations and partnerships as well as planning processes in influencing implementation. These are important to consider by government and public health organizations when promoting new or revised public health policies as they evolve over time. A successful policy implementation process in Ontario has helped to move public health towards the new vision. PMID- 27185038 TI - Variable RBE in proton therapy: comparison of different model predictions and their influence on clinical-like scenarios. AB - BACKGROUND: In proton radiation therapy a constant relative biological effectiveness (RBE) of 1.1 is usually assumed. However, biological experiments have evidenced RBE dependencies on dose level, proton linear energy transfer (LET) and tissue type. This work compares the predictions of three of the main radio-biological models proposed in the literature by Carabe-Fernandez, Wedenberg, Scholz and coworkers. METHODS: Using the chosen models, a spread-out Bragg peak (SOBP) as well as two exemplary clinical cases (single field and two fields) for cranial proton irradiation, all delivered with state-of-the-art pencil-beam scanning, have been analyzed in terms of absorbed dose, dose-averaged LET (LET D ), RBE-weighted dose (D RBE) and biological range shift distributions. RESULTS: In the systematic comparison of RBE predictions by the three models we could show different levels of agreement depending on (alpha/beta) x and LET values. The SOBP study emphasizes the variation of LET D and RBE not only as a function of depth but also of lateral distance from the central beam axis. Application to clinical-like scenario shows consistent discrepancies from the values obtained for a constant RBE of 1.1, when using a variable RBE scheme for proton irradiation in tissues with low (alpha/beta) x , regardless of the model. Biological range shifts of 0.6- 2.4 mm (for high (alpha/beta) x ) and 3.0 - 5.4 mm (for low (alpha/beta) x ) were found from the fall-off analysis of individual profiles of RBE-weighted fraction dose along the beam penetration depth. CONCLUSIONS: Although more experimental evidence is needed to validate the accuracy of the investigated models and their input parameters, their consistent trend suggests that their main RBE dependencies (dose, LET and (alpha/beta) x ) should be included in treatment planning systems. In particular, our results suggest that simpler models based on the linear-quadratic formalism and LETD might already be sufficient to reproduce important RBE dependencies for re evaluation of plans optimized with the current RBE = 1.1 approximation. This approach would be a first step forward to consider RBE variations in proton therapy, thus enabling a more robust choice of biological dose delivery. The latter could in turn impact clinical outcome, especially in terms of reduced toxicities for tumors adjacent to organs at risk. PMID- 27185040 TI - Ultralow-phase-noise millimetre-wave signal generator assisted with an electro optics-modulator-based optical frequency comb. AB - Low-noise millimetre-wave signals are valuable for digital sampling systems, arbitrary waveform generation for ultra-wideband communications, and coherent radar systems. However, the phase noise of widely used conventional signal generators (SGs) will increase as the millimetre-wave frequency increases. Our goal has been to improve commercially available SGs so that they provide a low phase-noise millimetre-wave signal with assistance from an electro-optics modulator-based optical frequency comb (EOM-OFC). Here, we show that the phase noise can be greatly reduced by bridging the vast frequency difference between the gigahertz and terahertz ranges with an EOM-OFC. The EOM-OFC serves as a liaison that magnifies the phase noise of the SG. With the EOM-OFC used as a phase noise "booster" for a millimetre-wave signal, the phase noise of widely used SGs can be reduced at an arbitrary frequency f (6 ? f ? 72 GHz). PMID- 27185041 TI - Transitioning a home telehealth project into a sustainable, large-scale service: a qualitative study. AB - BACKGROUND: This study was a component of the Flinders Telehealth in the Home project, which tested adding home telehealth to existing rehabilitation, palliative care and geriatric outreach services. Due to the known difficulty of transitioning telehealth projects services, a qualitative study was conducted to produce a preferred implementation approach for sustainable and large-scale operations, and a process model that offers practical advice for achieving this goal. METHODS: Initially, semi-structured interviews were conducted with senior clinicians, health service managers and policy makers, and a thematic analysis of the interview transcripts was undertaken to identify the range of options for ongoing operations, plus the factors affecting sustainability. Subsequently, the interviewees and other decision makers attended a deliberative forum in which participants were asked to select a preferred model for future implementation. Finally, all data from the study was synthesised by the researchers to produce a process model. RESULTS: 19 interviews with senior clinicians, managers, and service development staff were conducted, finding strong support for home telehealth but a wide diversity of views on governance, models of clinical care, technical infrastructure operations, and data management. The deliberative forum worked through these options and recommended a collaborative consortium approach for large-scale implementation. The process model proposes that the key factor for large-scale implementation is leadership support, which is enabled by 1) showing solutions to the problems of service demand, budgetary pressure and the relationship between hospital and primary care, 2) demonstrating how home telehealth aligns with health service policies, and 3) achieving clinician acceptance through providing evidence of benefit and developing new models of clinical care. Two key actions to enable change were marketing telehealth to patients, clinicians and policy-makers, and building a community of practice. CONCLUSIONS: The implementation of home telehealth services is still in an early stage. Change agents and a community of practice can contribute by marketing telehealth, demonstrating policy alignment and providing potential solutions for difficult health services problems. This should assist health leaders to move from trials to large-scale services. PMID- 27185042 TI - Association between telomere length and survival in cancer patients: a meta analysis and review of literature. AB - The relationship between telomere length and cancer survival has been widely studied. To gain a deeper insight, we reviewed the published studies. A total of 29 studies evaluated telomere length in the peripheral blood; 22 studies evaluated telomere length in the tumor tissue. First, in the peripheral blood studies, for solid tumor patients with shortened telomere length, the combined hazard ratios (HRs) for mortality and tumor progression were 1.21 (95%CI, 1.10 1.32) and 1.71 (95%CI, 1.37-2.13), respectively. Meanwhile, in hematology malignancy, the combined HRs for mortality and tumor progression were 2.83 (95%CI, 2.14-3.74) and 2.65 (95%CI, 2.18-3.22), respectively. Second, in the studies that use tumor tissue, for patients with shortened telomeres, the combined HRs for mortality and tumor progression were 1.26 (95%CI, 0.95-1.66) and 1.65 (95%CI, 1.26-2.15), respectively. In the studies that calculate the telomere length ratios of tumor tissue to adjacent normal mucosa, for patients with lower telomere length ratios, the combined HRs were 0.66 (95%CI, 0.53-0.83) and 0.74 (95%CI, 0.41-1.32) for mortality and tumor progression, respectively. In conclusion, shortened telomere in peripheral blood and tumor tissue might indicate poor survival for cancer patients. However, by calculating the telomere length ratios of tumor tissue to adjacent normal mucosa, the lower ratio might indicate better survival. PMID- 27185043 TI - The effect of age on outcome after intra-arterial treatment in acute ischemic stroke: a MR CLEAN pretrial study. AB - BACKGROUND: In recent randomized controlled trials (RCTs) intra-arterial treatment (IAT) has been proven effective and safe for patients with acute ischemic stroke (AIS). So far, there seemed to be no interaction between older age (>80) and main treatment effect. We studied the association of older age with outcome and adverse events after IAT in a cohort of intra arterially treated patients. METHODS AND FINDINGS: Data from all AIS patients with proven proximal anterior circulation cerebral artery occlusion who were intra arterially treated between 2002 until the start of the MR CLEAN trial were studied retrospectively. Duration of the procedure, recanalization (Thrombolysis In Cerebral Infarction score (TICI)), early neurological recovery (i.e. decrease on NIHSS of >= 8 points) after one week or at discharge, good functional outcome at discharge by modified Rankin Scale (mRS <= 2) and the occurrence of neurological and non neurological adverse events were assessed and the association with age was investigated. In total 315 patients met our inclusion criteria. Median age was 63 years (range 22-93) and 17 patients (5.4%) were over 80. Age was inversely associated with good functional outcome (adjusted Odds Ratio (aOR) 0.80, 95% CI: 0.66-0.98) for every 10 years increase of age. Age was not associated with longer duration of the procedure, lower recanalization rate or less early neurological recovery. The risk of all adverse events (aOR 1.27; 95% CI: 1.08-1.50) and non neurological adverse events (aOR 1.34; 95% CI: 1.11-1.61) increased, but that of peri-procedural adverse events (aOR 0.79; 95% CI: 0.66-0.94) decreased with age. CONCLUSION: Higher age is inversely associated with good functional outcome after IAT in patients with AIS. However, treatment related adverse events are not related to age. These findings may help decision making when considering treatment of older patients with AIS. PMID- 27185044 TI - The influence of the modulus-density relationship and the material mapping method on the simulated mechanical response of the proximal femur in side-ways fall loading configuration. AB - Contributing to slow advance of finite element (FE) simulations for hip fracture risk prediction, into clinical practice, could be a lack of consensus in the biomechanics community on how to map properties to the models. Thus, the aim of the present study was first, to systematically quantify the influence of the modulus-density relationship (E-rho) and the material mapping method (MMM) on the predicted mechanical response of the proximal femur in a side-ways fall (SWF) loading configuration and second, to perform a model-to-model comparison of the predicted mechanical response within the femoral neck for all the specimens tested in the present study, using three different modelling techniques that have yielded good validation outcome in terms of surface strain prediction and whole bone response according to the literature. We found the outcome to be highly dependent on both the E-rho relationship and the MMM. In addition, we found that the three modelling techniques that have resulted in good validation outcome in the literature yielded different principal strain prediction both on the surface as well as internally in the femoral neck region of the specimens modelled in the present study. We conclude that there exists a need to carry out a more comprehensive validation study for the SWF loading mode to identify which combination of MMMs and E-rho relationship leads to the best match for whole bone and local mechanical response. The MMMs tested in the present study have been made publicly available at https://simtk.org/home/mitk-gem. PMID- 27185045 TI - Pump function curve shape for a model lymphatic vessel. AB - The transport capacity of a contractile segment of lymphatic vessel is defined by its pump function curve relating mean flow-rate and adverse pressure difference. Numerous system characteristics affect curve shape and the magnitude of the generated flow-rates and pressures. Some cannot be varied experimentally, but their separate and interacting effects can be systematically revealed numerically. This paper explores variations in the rate of change of active tension and the form of the relation between active tension and muscle length, factors not known from experiment to functional precision. Whether the pump function curve bends toward or away from the origin depends partly on the curvature of the passive pressure-diameter relation near zero transmural pressure, but rather more on the form of the relation between active tension and muscle length. A pump function curve bending away from the origin defines a well performing pump by maximum steady output power. This behaviour is favoured by a length/active-tension relationship which sustains tension at smaller lengths. Such a relationship also favours high peak mechanical efficiency, defined as output power divided by the input power obtained from the lymphangion diameter changes and active-tension time-course. The results highlight the need to pin down experimentally the form of the length/active-tension relationship. PMID- 27185046 TI - [Intraoperative echocardiography guidelines in Brazil - Is it time for a task force?] AB - BACKGROUND AND OBJECTIVES: The Brazilian Society of Anesthesiology (SBA) has been promoting continuing education in intraoperative echocardiography in Brazil since 2011, with the implementation of an Intraoperative Echocardiography Course (ETI/SBA). Although echocardiography is a reality of anesthesiology practice in Brazil, we still do not have an established policy on the area of expertise, job training, and recognition by the other societies, such as the Brazilian Society of Cardiology (SBC). The aim of this paper is to contextualize the anesthesiology in the intraoperative echocardiography in Brazil and promote a discussion on the formation of a Task Force along with the SBC to begin drawing up the Brazilian Guidelines on Intraoperative Echocardiography. CASE REPORT: The first reports on the involvement of anesthesiology in Brazil with intraoperative echocardiography are from the 80s and 90s. However, this technique implementation in routine practice in the Brazilian anesthesiology occurred in 2011 with the formation of the ETI/SBA Course. Since then, the SBA has been promoting a continuing education of its members and disseminating the ETI/SBA Course throughout Brazil. More than 200 associates have taken this course, and the vast majority works with cardiac surgery. CONCLUSION: Intraoperative echocardiography is a reality in the practice of the Brazilian anesthesiology, and the ETI/SBA Course has been promoting its continuing education, however, we still do not have a grounded guideline. As occurred in major worldwide centers, we have to promote a Task Force along with the SBC in order to begin the drawing up of the Brazilian Guidelines on Intraoperative Echocardiography. PMID- 27185047 TI - Interactions of the "piano-stool" [ruthenium(II)(eta(6) -arene)(quinolone)Cl](+) complexes with water; DFT computational study. AB - Full optimizations of stationary points along the reaction coordinate for the hydration of several quinolone Ru(II) half-sandwich complexes were performed in water environment using the B3PW91/6-31+G(d)/PCM/UAKS method. The role of diffuse functions (especially on oxygen) was found crucial for correct geometries along the reaction coordinate. Single-point (SP) calculations were performed at the B3LYP/6-311++G(2df,2pd)/DPCM/saled-UAKS level. In the first part, two possible reaction mechanisms-associative and dissociative were compared. It was found that the dissociative mechanism of the hydration process is kinetically slightly preferred. Another important conclusion concerns the reaction channels. It was found that substitution of chloride ligand (abbreviated in the text as dechlorination reaction) represents energetically and kinetically the most feasible pathway. In the second part the same hydration reaction was explored for reactivity comparison of the Ru(II)-complexes with several derivatives of nalidixic acid: cinoxacin, ofloxacin, and (thio)nalidixic acid. The hydration process is about four orders of magnitude faster in a basic solution compared to neutral/acidic environment with cinoxacin and nalidixic acid as the most reactive complexes in the former and latter environments, respectively. The explored hydration reaction is in all cases endergonic; nevertheless the endergonicity is substantially lower (by ~6 kcal/mol) in basic environment. (c) 2016 Wiley Periodicals, Inc. PMID- 27185048 TI - Pilot evaluation of ivacaftor for chronic bronchitis. PMID- 27185049 TI - Detection of hepatitis C virus (HCV) core-specific antibody suggests occult HCV infection among blood donors. AB - BACKGROUND: Blood transfusion safety is based on reliable donor screening for transmissible infections such as the hepatitis C virus (HCV) infection. STUDY DESIGN AND METHODS: A novel HCV core-specific antibody was assayed on random single donations from 2007 first-time blood donors who tested negative for anti HCV and HCV RNA on routine screening. Sample collection broke the code between donations and donors for ethical reasons. RESULTS: Forty-two donations (2.1%) displayed reactivity in the novel test. The specificity of the reactivity was evaluated by a peptide inhibition assay, and testing against additional nonoverlapping HCV core peptide epitopes and other HCV antigens was performed on these samples. Six donations (14.3%; 0.30% from the total) were considered to contain anti-HCV after such supplemental testing. HCV RNA detection was also performed in peripheral blood mononuclear cells (PBMNCs) and serum or plasma samples from reactive donors after virus concentration by ultracentrifugation. HCV RNA tested negative in all PBMNCs samples, and a very low amount of viral genome was detected in serum or plasma concentrates from three anti-HCV core reactive donors (7.1%) but not among concentrates from 100 randomly selected nonreactive donors. Sequencing of these polymerase chain reaction products revealed differences between the isolates that excluded partially sample contamination from a common source. CONCLUSION: These findings argue in favor of an ongoing occult HCV infection among these blood donors and account for some rather low, but perhaps not negligible, infection risk for such donations. Future studies involving larger samples of donations from traceable donors would enlighten the significance of these findings for the viral safety of the blood supply. PMID- 27185051 TI - Synthesis of Tunable Band Gap Semiconductor Nickel Sulphide Nanoparticles: Rapid and Round the Clock Degradation of Organic Dyes. AB - Controlled shape and size with tuneable band gap (1.92-2.41 eV), nickel sulphide NPs was achieved in presence of thiourea or thioacetamide as sulphur sources with the variations of temperature and capping agents. Synthesized NPs were fully characterized by powder XRD, IR, UV-vis, DRS, FE-SEM, TEM, EDX, XPS, TGA and BET. Capping agent, temperature and sulphur sources have significant role in controlling the band gaps, morphology and surface area of NPs. The catalytic activities of NPs were tested for round the clock (light and dark) decomposition of crystal violet (CV), rhodamine B (RhB), methylene blue (MB), nile blue (NB) and eriochrome black T (EBT). Agitation speed, temperature, pH and ionic strength have significant role on its catalytic activities. The catalyst was found to generate reactive oxygen species (ROS) both in presence and absence of light which is responsible for the decomposition of dyes into small fractions, identified with ESI-mass spectra. PMID- 27185050 TI - Epitope mapping by a Wnt-blocking antibody: evidence of the Wnt binding domain in heparan sulfate. AB - Heparan sulfate (HS) is a polysaccharide known to modulate many important biological processes, including Wnt signaling. However, the biochemical interaction between HS and Wnt molecules is not well characterized largely due to the lack of suitable methods. To determine the Wnt binding domain in HS, we used a Wnt signaling-inhibitory antibody (HS20) and a panel of synthetic HS oligosaccharides with distinct lengths and sulfation modifications. We found that the binding of HS20 to heparan sulfate required sulfation at both the C2 position (2-O-sulfation) and C6 position (6-O-sulfation). The oligosaccharides with the greatest competitive effect for HS20 binding were between six and eight saccharide residues in length. Additionally, a four residue-long oligosaccharide could also be recognized by HS20 if an additional 3-O-sulfation modification was present. Furthermore, similar oligosaccharides with 2-O, 6-O and 3-O-sulfations showed inhibition for Wnt activation. These results have revealed that HS20 and Wnt recognize a HS structure containing IdoA2S and GlcNS6S, and that the 3-O sulfation in GlcNS6S3S significantly enhances the binding of both HS20 and Wnt. This study provides the evidence for identifying the Wnt binding domain in HS and suggests a therapeutic approach to target the interaction of Wnt and HS in cancer and other diseases. PMID- 27185053 TI - An examination of racial differences in 5-year survival of cervical cancer among African American and white American women in the southeastern US from 1985 to 2010. AB - Disparities in Cervical Cancer (CC) mortality outcomes between African American (AA) and White women have been studied for decades. However, conclusions about the effect of race on CC survival differ across studies. This study assessed differences in CC survival between AA and White women diagnosed between 1985 and 2010 and treated at two major hospitals in the southeastern US. The study sample included 925 AA and 1192 White women diagnosed with cervical adenocarcinoma, adenosquamous cell carcinoma, or squamous cell carcinoma. Propensity score adjustment and matching were employed to compare 5-year survival between the two racial groups. Crude comparisons suggested relevant racial differences in survival. However, the racial differences became of small magnitude after propensity-score adjustment and in matched analyses. Nonlinear models identified age at diagnosis, cancer stage, mode of treatment, and histological subtype as the most salient characteristics predicting 5-year survival of CC, yet these characteristics were also associated with race. Crude racial differences in survival might be partly explained by underlying differences in the characteristics of racial groups, such as age at diagnosis, histological subtype, cancer stage, and the mode of treatment. The study results highlight the need to improve access to early screening and treatment opportunities for AA women to improve posttreatment survival from CC. PMID- 27185054 TI - Solid phase extraction, separation and preconcentration of rare elements thorium(IV), uranium(VI), zirconium(IV), cerium(IV) and chromium(III) amid several other foreign ions with eriochrome black T anchored to 3-D networking silica gel. AB - The present work reports the systematic studies on extraction, separation and preconcentration of Th(IV), U(VI), Zr(IV), Ce(IV) and Cr(III) amid several other foreign ions using EBT anchored {SiO2}n3-D microarray. The effect of various sorption parameters, such as pH, concentration, temperature, sample volume, flow rate and co-existing foreign ions were investigated. Quantitative sorption was ensured at solution pH: 6.0-6.5 for Th(IV), Ce(IV), Cr(III) and pH: 2.75-3.0 for Zr(IV), U(VI) couple. Analysis on extracted species and extraction sites reveals that [Th4(MU(2)-OH)8(H2O)4](8+), [Ce6(MU(2)-OH)12(H2O)5](12+), [Cr3(MU(2) OH)4(H2O)](5+), [(UO2)3(MU(2)-OH)5(H2O)3](+) and [Zr4(MU(2)-OH)8(H2O)0.5](8+) for the respective metal ions gets extracted at HOMO of the extractor. HOMO-{metal ion species} was found to be 1:1 complexation. Sorption was endothermic, entropy gaining, instantaneous and spontaneous in nature. A density functional theory (DFT) calculation has been performed to analyze the 3-D structure and electronic distribution of the synthesized extractor. PMID- 27185055 TI - Intrinsic advantages of packed capillaries over narrow-bore columns in very high pressure gradient liquid chromatography. AB - 250MUm*100mm fused silica glass capillaries were packed with 1.8MUm high-strength silica (HSS) fully porous particles. They were prepared without bulky stainless steel endfittings and metal frits, which both generate significant sample dispersion. The isocratic efficiencies and gradient peak capacities of these prototype capillary columns were measured for small molecules (n-alkanophenones) using a home-made ultra-low dispersive micro-HPLC instrument. Their resolution power was compared to that of standard 2.1mm*100mm very high-pressure liquid chromatography (vHPLC) narrow-bore columns packed with the same particles. The results show that, for the same column efficiency (25000 plates) and gradient steepness (0.04min(-1)), the peak capacity of the 250MUm i.d. capillary columns is systematically 15-20% higher than that of the 2.1mm i.d. narrow-bore columns. A validated model of gradient chromatography enabled one to predict accurately the observed peak capacities of the capillary columns for non-linear solvation strength retention behavior and under isothermal conditions. Thermodynamics applied to the eluent quantified the temperature difference for the thermal gradients in both capillary and narrow-bore columns. Experimental data revealed that the gradient peak capacity is more affected by viscous heating than the column efficiency. Unlike across 2.1mm i.d. columns, the changes in eluent composition across the 250MUm i.d. columns during the gradient is rapidly relaxed by transverse dispersion. The combination of (1) the absence of viscous heating and (2) the high uniformity of the eluent composition across the diameter of capillary columns explains the intrinsic advantage of capillary over narrow-bore columns in gradient vHPLC. PMID- 27185052 TI - Biomonitoring of concurrent exposure to ochratoxin A and citrinin in pregnant women in Bangladesh. AB - Ochratoxin A (OTA) and citrinin (CIT) are both nephrotoxic and teratogenic in animals, and the occurrence of these mycotoxins in food may cause adverse health effects in humans. Data on the combined exposure to these food contaminants are still scarce, especially in pregnancy. Therefore, a biomonitoring study was conducted to determine the presence of urinary biomarkers of exposure to OTA and CIT in pregnant women in Bangladesh. In total, 54 spot urine samples were collected from residents of a rural and a suburban area of the Savar region in Dhaka district for analysis of OTA and CIT urinary biomarkers by previously validated HPLC-FD and LC-MS/MS methods. Most urines were positive for OTA and CIT biomarkers, with OTA being detected in 93 % (range 0.01-0.84 ng/mL) and CIT biomarkers in 87 % (range 0.02-6.93 ng/mL) of all samples. The mean levels of OTA were different between the rural (0.06 +/- 0.07 ng/mL) and suburban (0.15 +/- 0.19 ng/mL) study participants. CIT and its metabolite dihydrocitrinone (HO-CIT) were more than twofold higher in the rural (0.42 +/- 1.20 and 0.55 +/- 1.04 ng/mL, respectively) than the suburban (CIT 0.15 +/- 0.13 ng/mL; HO-CIT 0.23 +/- 0.18 ng/mL) participants. When a provisional daily intake for CIT was calculated, it exceeded the preliminary tolerable value set by European Food Safety Authority (0.2 MUg/kg/day) in 9 % of the rural participants but in none of the urban participants. Urinary biomarker levels for OTA and CIT did not show significant association with intake of certain types of food consumed by the pregnant women, although total CIT biomarker levels were considerably higher among participants who consumed more rice in a day. Overall, this study indicates a frequent co exposure to OTA and CIT among pregnant women in Bangladesh, at levels similar to those determined recently in the general population of this country. PMID- 27185056 TI - Liquid chromatography and supercritical fluid chromatography as alternative techniques to gas chromatography for the rapid screening of anabolic agents in urine. AB - This work describes the development of two methods involving supported liquid extraction (SLE) sample treatment followed by ultra-high performance liquid chromatography or ultra-high performance supercritical fluid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS and UHPSFC-MS/MS) for the screening of 43 anabolic agents in human urine. After evaluating different stationary phases, a polar-embedded C18 and a diol columns were selected for UHPLC-MS/MS and UHPSFC-MS/MS, respectively. Sample preparation, mobile phases and MS conditions were also finely tuned to achieve highest selectivity, chromatographic resolution and sensitivity. Then, the performance of these two methods was compared to the reference routine procedure for steroid analyses in anti-doping laboratories, which combines liquid-liquid extraction (LLE) followed by gas chromatography coupled to tandem mass spectrometry (GC-MS/MS). For this purpose, urine samples spiked with the compounds of interest at five different concentrations were analyzed using the three analytical platforms. The retention and selectivity of the three techniques were very different, ensuring a good complementarity. However, the two new methods displayed numerous advantages. The overall procedure was much faster thanks to high throughput SLE sample treatment using 48-well plates and faster chromatographic analysis. Moreover, the highest sensitivity was attained using UHPLC-MS/MS with 98% of the doping agents detected at the lowest concentration level (0.1ng/mL), against 76% for UHPSFC-MS/MS and only 14% for GC-MS/MS. Finally, the weakest matrix effects were obtained with UHPSFC-MS/MS with 76% of the analytes displaying relative matrix effect between 20 and 20%, while the GC-MS/MS reference method displayed very strong matrix effects (over 100%) for all of the anabolic agents. PMID- 27185058 TI - The Road to MOF-Related Functional Materials and Beyond: Desire, Design, Decoration, and Development. AB - Metal-organic frameworks (MOFs), which are known as a class of porous coordination polymers, have proven to be of great significance to manifold applications, owing to their fascinating topology, ultrahigh porosity, enormous internal surface area, and the combination of being as rigid as inorganic materials and as flexible as organic materials . In this review, we give a concise history of the development of MOFs as functional materials prior to our entry into this area in 2006, then a summary of our road to participate in and extend the outline of the research in MOFs chemistry, as well as the challenge in further designing applicable functional materials. We describe not only the road of evolution from the past, present, and future of this chemistry, but also the road to finalize a functional material from the desire to the design, synthesis, and postmodification of a MOF. Throughout the review, we particularly emphasize the improvements in the application of MOFs as heterogeneous catalysts, such as employing MOFs as one component for the construction of composites, and their extended scope in tough catalytic reactions. Examples of applications in gas storage and separation, small molecular sensing, and our perspectives for future applications triggered by MOFs, are also introduced. PMID- 27185057 TI - How do Physicians Decide to Refer Their Patients for Psychiatric Genetic Counseling? A Qualitative Study of Physicians' Practice. AB - Psychiatric genetic counseling (PGC) is an emerging specialty discipline within the genetic counseling profession. A specialist PGC service was founded in 2012 in Vancouver, Canada, and though patient benefits have been demonstrated, many physicians do not regularly refer patients to the service despite awareness of its availability. We conducted a qualitative study involving semi-structured telephone interviews with Vancouver-based physicians who were aware of the PGC service to explore this phenomenon. Interviews were audio-recorded, transcribed verbatim, coded, and analysed for emergent themes. Consistent with a grounded theory approach, constant comparison was employed throughout data collection and analysis. Analyses of interviews conducted with 12 physicians revealed that referral practices were informed by perceptions about the purpose of PGC and interpretation of patient cues. Physicians perceived PGC as an information focused intervention, and considered referral when patients explicitly expressed desire for information about recurrence risk or etiology that they felt unable to adequately address themselves. Even when physicians identified psychotherapeutic benefits of PGC, patient needs of this nature were not perceived as cues prompting referral to PGC. These data suggest that further work is necessary to position PGC in physicians' minds as a service that could potentially benefit most individuals with psychiatric disorders and their families, and that it encompasses more than information provision. It is important to increase physicians' awareness of the complementary role that genetic counselors can play to that of the physician in providing psychotherapeutically oriented counselling about illness etiology. PMID- 27185060 TI - A critical review of complementary and alternative medicine use by women with cyclic perimenstrual pain and discomfort: a focus upon prevalence, patterns and applications of use and users' motivations, information seeking and self perceived efficacy. AB - INTRODUCTION: Complementary and alternative medicine (CAM) is used for treating cyclic perimenstrual pain and discomfort. This critical review examines women's reported CAM use, its perceived effectiveness and information relating to women's attitudes, behaviors, motivations and patterns of CAM use in its treatment. MATERIAL AND METHODS: An extensive search of the main medical databases EBSCO, CINAHL, Medline, AMED and SCOPUS, as well as additional hand searches, was conducted. Papers included were confined to those that had been peer-reviewed, written in English and that contained original research into CAM use for cyclic perimenstrual pain and discomfort among adult women. RESULTS: CAM, particularly herbal medicine, nutritional supplements and massage, is widely used for a range of cyclic perimenstrual pain and discomfort symptoms. A large number of CAM modalities are adopted, often simultaneously and with little professional oversight. Women's assessment of efficacy of different CAM modalities is positive, though the majority of users are self-prescribing apparently without professional guidance. Although the uptake of CAM for cyclic perimenstrual pain and discomfort is widespread, few empirical data are available regarding which women are using CAM, their motivations for doing so and, importantly, the sources through which women receive information about CAM. CONCLUSIONS: This review highlights the extensive use of (often self-prescribed) CAM in a number of countries to alleviate the widespread symptoms of cyclic perimenstrual pain and discomfort. An understanding of all health care use by women with perimenstrual pain and discomfort is vital to help ensure safe, effective and coordinated health care that can lead to optimal patient outcomes. PMID- 27185059 TI - LOGIQA: a database dedicated to long-range genome interactions quality assessment. AB - BACKGROUND: Proximity ligation-mediated methods are essential to study the impact of three-dimensional chromatin organization on gene programming. Albeit significant progress has been made in the development of computational tools that assess long-range chromatin interactions, next to nothing is known about the quality of the generated datasets. METHOD: We have developed LOGIQA ( www.ngs qc.org/logiqa ), a database hosting quality scores for long-range genome interaction assays, accessible through a user-friendly web-based environment. RESULTS: Currently, LOGIQA harbors QC scores for >900 datasets, which provides a global view of their relative quality and reveals the impact of genome size, coverage and other technical aspects. LOGIQA provides a user-friendly dataset query panel and a genome viewer to assess local genome-interaction maps at different resolution and quality-assessment conditions. CONCLUSIONS: LOGIQA is the first database hosting quality scores dedicated to long-range chromatin interaction assays, which in addition provides a platform for visualizing genome interactions made available by the scientific community. PMID- 27185061 TI - Cutaneous cylindroma: it's all about MYB. AB - Cutaneous cylindroma is a rare benign tumour that occasionally turns into malignant cylindrocarcinoma. The cancer can be sporadic or emerge in the context of Brooke-Spiegler syndrome (BSS), an inheritable condition characterized by mutation of the gene CYLD, encoding a tumour suppressor protein that controls the activity of the transcription factor NF-kB. Sporadic cylindromas present histological features shared with adenoid cystic carcinoma (ACC), a head and neck cancer originating from salivary or other exocrine glands. Like ACCs, sporadic cylindromas express, although at lower frequency, the aberrant fusion transcript MYB-NFIB. In a paper recently published in the Journal of Pathology, the research teams led by Neil Rajan and Goran Stenman demonstrate that CYLD-defective cyclindromas in BSS patients are negative for the MYB-NFIB fusion. Only the wild type MYB oncoprotein is activated in the majority of these tumours. RNA interference studies in cells derived from BSS patients indicate that ablating MYB expression results in a striking reduction of cylindroma cell proliferation, suggesting that MYB plays a pivotal role in the biology of this cancer. The take home message of the study is that activation of MYB, in its wild-type form or fusion derivatives, is a common feature of spontaneous and hereditary cylindromas, constituting a potentially actionable therapeutic target. Copyright (c) 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID- 27185062 TI - ADVICE for a healthier life: Adult Vaccination Campaign in Europe. AB - Immunization is one of the most effective public health measures to prevent disease. Despite relatively good vaccination rates in childhood in many parts of the world, vaccines to prevent diseases are underused in the adult population and adult vaccination rates are still far below the target. The European Federation of Internal Medicine (EFIM), declared that 'internal medicine must focus on better care for individuals, better health care for populations and lower costs'. Adult vaccination is a good example of a public health initiative aimed at reducing morbidity and mortality, but awareness of the need for adult vaccination and uptake of the programs across Europe is variable. The Adult Vaccination Campaign in Europe (ADVICE) was developed with an aim to raise awareness for adult vaccination and to understand the dynamics of the vaccination practices and the possible barriers against achieving targeted vaccination rates in Europe. In order to reach vaccination targets, we need evidence based, up to date guidelines; recommendations at national and international levels; surveillance for vaccination rates; and opportunities to provide vaccines more readily. Leadership at a European level and a firm research and action agenda are crucial. The European Federation of Internal Medicine can take the lead as it declared its interest on 'better care for individuals, better health care for populations'. Hence, we consider ADVICE a very timely and very valuable initiative to draw a roadmap to improve adult vaccination rates in Europe. PMID- 27185063 TI - Effects of zinc oxide nanoparticles on human coronary artery endothelial cells. AB - Inhalation of zinc oxide (ZnO) metal fumes is known to cause metal fume fever and to have systemic effects; however, the effects of ZnO nanoparticles (ZnONPs) on the cardiovascular system remain unclear. The objective of this study was to investigate the cardiovascular toxicity of ZnONPs. Human coronary artery endothelial cells (HCAECs) were exposed to ZnONPs of different sizes to investigate the cell viability, 8-hydroxy-2'-deoxyguanosine (8-OHdG), interleukin (IL)-6, nitric oxide (NO), and regulation of cardiovascular disease-related genes. Exposure of HCAECs to ZnONPs resulted in decreased cell viability and increased levels of 8-OHdG, IL-6, and NO. Downregulation of cardiovascular associated genes was observed in response to ZnONPs in HCAECs determined by qPCR, suggesting that the calcium signaling pathway, neuroactive ligand-receptor interaction, hypertrophic cardiomyopathy, dilated cardiomyopathy, and renin angiotensin system are important affected pathways in response to ZnONPs. Furthermore, we observed a significant response of AGTR1 to ZnONP exposure in HCAECs. Our results suggest that ZnONPs cause toxicity to HCAECs, which could be associated with cardiovascular dysfunction. PMID- 27185064 TI - Kruppel homolog 1 and E93 mediate Juvenile hormone regulation of metamorphosis in the common bed bug, Cimex lectularius. AB - The common bed bug is an obligate hematophagous parasite of humans. We studied the regulation of molting and metamorphosis in bed bugs with a goal to identify key players involved. qRT-PCR studies on the expression of genes known to be involved in molting and metamorphosis showed high levels of Kruppel homolog 1 [Kr h1, a transcription factor that plays key roles in juvenile hormone (JH) action] mRNA in the penultimate nymphal stage (N4). However, low levels of Kr-h1 mRNA were detected in the fifth and last nymphal stage (N5). Knockdown of Kr-h1 in N4 resulted in a precocious development of adult structures. Kr-h1 maintains the immature stage by suppressing E93 (early ecdysone response gene) in N4. E93 expression increases during the N5 in the absence of Kr-h1 and promotes the development of adult structures. Knockdown of E93 in N5 results in the formation of supernumerary nymphs. The role of JH in the suppression of adult structures through interaction with Kr-h1 and E93 was also studied by the topical application of JH analog, methoprene, to N5. Methoprene induced Kr-h1 and suppressed E93 and induced formation of the supernumerary nymph. These data show interactions between Kr-h1, E93 and JH in the regulation of metamorphosis in the bed bugs. PMID- 27185065 TI - Cardiac assessment prior to non-cardiac surgery. AB - BACKGROUND: Increasingly, patients undergoing non-cardiac surgery are older and have more comorbidities yet preoperative cardiac assessment appears haphazard and unsystematic. We hypothesised that patients at high cardiac risk were not receiving adequate cardiac assessment, and patients with low-cardiac risk were being over-investigated. AIMS: To compare in a representative sample of patients undergoing non-cardiac surgery the use of cardiac investigations in patients at high and low preoperative cardiac risk. METHODS: We examined cardiac assessment patterns prior to elective non-cardiac surgery in a representative sample of patients. Cardiac risk was calculated using the Revised Cardiac Risk Index. RESULTS: Of 671 patients, 589 (88%) were low risk and 82 (12%) were high risk. We found that nearly 14% of low-risk and 45% of high-risk patients had investigations for coronary ischaemia prior to surgery. Vascular surgery had the highest rate of investigation (38%) and thoracic patients the lowest rate (14%). Whilst 78% of high-risk patients had coronary disease, only 46% were on beta blockers, 49% on aspirin and 77% on statins. For current smokers (17.3% of cohort, n = 98), 60% were advised to quit pre-op. CONCLUSIONS: Practice patterns varied across surgical sub-types with low-risk patients tending to be over investigated and high-risk patients under-investigated. A more systemised approach to this large group of patients could improve clinical outcomes, and more judicious use of investigations could lower healthcare costs and increase efficiency in managing this cohort. PMID- 27185066 TI - Deep Photoacoustic/Luminescence/Magnetic Resonance Multimodal Imaging in Living Subjects Using High-Efficiency Upconversion Nanocomposites. AB - A gadolinium-doped multi-shell upconversion nanoparticle under 800 nm excitation is synthesized with a 10-fold fluorescence-intensity enhancement over that under 980 nm. The nanoformulations exhibit excellent photoacoustic/luminescence/magnetic resonance tri-modal imaging capabilities, enabling visualization of tumor morphology and microvessel distribution at a new imaging depth. PMID- 27185067 TI - Nonlinear response surface in the study of interaction analysis of three combination drugs. AB - Few articles have been written on analyzing three-way interactions between drugs. It may seem to be quite straightforward to extend a statistical method from two drugs to three-drugs. However, there may exist more complex nonlinear response surface of the interaction index (II) with more complex local synergy and/or local antagonism interspersed in different regions of drug combinations in a three-drug study, compared in a two-drug study. In addition, it is not possible to obtain a four-dimensional (4D) response surface plot for a three-drug study. We propose an analysis procedure to construct the dose combination regions of interest (say, the synergistic areas with II<=0.9). First, use the model robust regression method (MRR), a semiparametric method, to fit the entire response surface of the II, which allows to fit a complex response surface with local synergy/antagonism. Second, we run a modified genetic algorithm (MGA), a stochastic optimization method, many times with different random seeds, to allow to collect as many feasible points as possible that satisfy the estimated values of II<=0.9. Last, all these feasible points are used to construct the approximate dose regions of interest in a 3D. A case study with three anti-cancer drugs in an in vitro experiment is employed to illustrate how to find the dose regions of interest. PMID- 27185068 TI - Effect of a polysaccharide from Poria cocos on humoral response in mice immunized by H1N1 influenza and HBsAg vaccines. AB - Poria cocos has a long history of medicinal use in China. Polysaccharides and their derivatives in the medicine exhibit many beneficial biological activities including anticancer, anti-inflammatory, antioxidant and antiviral activities. In this study, a new polysaccharide (PCP-II) was isolated from sclerotium of Poria cocos. Its physico-chemical characters were identified and its adjuvant activity was investigated in mice co-immunized with H1N1 influenza vaccine and hepatitis B surface antigen (HBsAg). The results revealed that PCP-II has a molecular weight of 29.0kDa. It was composed of fucose, mannose, glucose and galactose in molar ration of 1.00:1.63:0.16:6.29 respectively. Pharmacological data demonstrated that PCP-II increased antigen-specific antibody levels in mice immunized with influenza vaccine. PCP-II also elicited anti-HBsAg antibodies at significantly higher titers and generated robust and durable immunity compared to mice immunized with HBsAg-alum following two administrations. PCP-II improved proliferation of splenocytes, stimulated IL-12p70 and TNF-alpha productions in dendritic cells and macrophages respectively. These results suggested that PCP-II adjuvanted vaccines enhanced humoral and cellular immunity. PCP-II could be developed as an efficacious adjuvant in human and animal vaccines. PMID- 27185069 TI - Extracellular matrix-based cryogels for cartilage tissue engineering. AB - In this study, we investigated various highly porous extracellular matrix (ECM) based cryogels for cartilage tissue engineering. For the fabrication of ECM-based cryogels, either methacrylated chondroitin sulfate (MeCS) or methacrylated hyaluronic acid (MeHA) were cross-linked along with poly (ethylene glycol) diacrylates (PEGDA) via free radical polymerization under freezing conditions. This procedure induces ice crystallization (used as a porogen) prior polymer crosslinking in which, after complete cryopolymerization, a thawing process transforms the ice crystals into a unique interconnected macroporous structure within ECM-cryogels. The developed ECM-cryogels exhibited an average macroporosity of 75% and supported the infiltration of chondrocyteds. When rabbit chondrocytes were cultured on ECM-cryogels, MeCS-based cryogels stimulated aggrecan gene expression and GAG accumulation, whereas MeHA-based cryogels stimulated type II collagen gene expression and collagen accumulation. These results demonstrate that design of ECM-based cryogels can play an important role in promoting specific ECM proteins secretion for cartilage tissue engineering. PMID- 27185070 TI - Structural-functional insights and studies on saccharide binding of Sophora japonica seed lectin. AB - Functional and conformational transitions of the Sophora japonica seed lectin (SJL) were studied in detail using bioinformatics and biophysical tools. Homology model of the lectin displayed all the characteristics of the legume lectin monomer and the experimental observations correlated well with the structural information. In silico studies were performed by protein-ligand docking, calculating the respective binding energies and the residues involved in the interactions were derived from LigPlot(+) analysis. Fluorescence titrations showed three times higher affinity of T-antigen disaccharide than N-acetyl galactosamine (GalNAc) towards SJL indicating extended sugar binding site of the lectin. Thermodynamic parameters of T-antigen binding to SJL indicated the process to be endothermic and entropically driven while those of GalNAc showed biphasic process. SDS-PAGE showed post-translationally modified homotetrameric species of the lectin under native conditions. In presence of guanidine hydrochloride (0.5-5.0M), the tetramer first dissociated into dimers followed by unfolding of the protein as indicated by size exclusion chromatography, fluorescence and CD spectroscopy. Different structural rearrangements were observed during thermal denaturation of SJL at physiological pH 7.2, native pH 8.5 and molten globule inducing pH 1.0. Topological information revealed by solute quenching studies at respective pH indicated differential hydrophobic environment and charge density around tryptophan residues. PMID- 27185071 TI - Development of UV cross-linked gelatin coated electrospun poly(caprolactone) fibrous scaffolds for tissue engineering. AB - Cardiovascular disease is the leading cause of morbidity and mortality among industrialized countries. Vascular grafts are often required for the surgical treatments. Considering the limitations associated with the use of autografts and with the currently available synthetic materials, a growing demand in tissue engineered vascular grafts has been registered. During the work here described, electrospinning technique was used to prepared fibrous matrices to be applied as vascular implants. For that purpose, electrospun polycaprolactone (PCL) fibrous mats were produced and afterwards coated with different hydrogel formulations based in photocrosslinkable gelatin (GelMA) and the macromers poly(ethylene glycol) acrylate (PEGA) and poly(ethylene glycol) diacrylate (PEGDA). These were further photocrosslinked under UV irradiation using Irgacure(r) 2959 (by BASF) as the photoinitiator. The suitability of the coated scaffolds for the intended application, was evaluated by assessing their chemical/physical properties as well as their interaction with blood and endothelial cells. PMID- 27185072 TI - Psychiatric and Behavioural Disorders in Children with Epilepsy (ILAE Task Force Report): When should pharmacotherapy for psychiatric/behavioural disorders in children with epilepsy be prescribed? AB - The most important factor in deciding whether psychotropic medication should be prescribed is a meticulous assessment of the possible causes of the behavioural/psychiatric disturbance. This assessment should include a consideration of the possible roles of the epilepsy itself, treatment of the epilepsy, associated brain damage or dysfunction, reactions to the epilepsy and causes that are unrelated to the epilepsy or its treatment. If the epilepsy itself or antiepileptic drug treatment are responsible for the disorder then a review of antiepileptic medication is required. Contrary to popular myth, most psychotropic medications are not contraindicated in children with epilepsy. Treatment with methylphenidate, dexamfetamine, atomoxetine, clonidine or low-dose risperidone are unlikely to precipitate seizures. The selective serotonin reuptake inhibitors might protect against seizures but some of these are powerful enzyme inhibitors, implying that careful monitoring to avoid antiepileptic drug toxicity is recommended. In many cases, the appropriate approach will be through other interventions such as behavioural management or providing the young person with empowering strategies, implying that psychotropic pharmacotherapy should not be the first-line treatment. However, if assessment indicates that psychotropic medication is necessary, it can be of great benefit. PMID- 27185073 TI - Non-biased and complete case registration of lymphoid leukemia and lymphoma for five years: a first representative index of Japan from an epidemiologically stable Miyagi Prefecture. AB - Previous worldwide epidemiological studies on lymphoid leukemia and/or lymphoma (LL/L) had considerable bias because of difficulty in covering all clinical departments of hospitals in a restricted area (population base). These studies may not have reflected the actual number of newly diagnosed cases (incidence) strictly, or the true LL/L subtype frequencies. We searched all cases of newly diagnosed LL/L in Miyagi Prefecture over a 5-year period, including those that were discovered as LL/L sorely after autopsy. We registered the actual number of 2098 cases in the prefecture and calculated an accurate incidence rate (17.8 per 100,000 persons). Additionally, we identified more realistic and detailed frequencies of LL/L subtypes including the leukemic phase of some lymphomas. As Miyagi Prefecture is an area in which the population dynamics are relatively stable and representative of Japan, the result of our epidemiological study can be used as the first representative index of LL/L for Japan. PMID- 27185074 TI - A measurement framework for adherence in patient decision aid trials applied in a systematic review subanalysis. AB - OBJECTIVE: To explore how studies of decision aids conceptualize and measure adherence and to evaluate the effect of patient decision aids on adherence. STUDY DESIGN AND SETTING: A subanalysis of adherence studies included in the 2014 Cochrane review on patient decision aids. An adherence framework for decision aid trials is presented which includes two types of adherence: "adherence to choice" and "adherence to treatment." Included studies were classified based on the adherence framework, and their impact on adherence was assessed. RESULTS: Thirteen trials involving 2,115 patients were included. Of these 13, eight measured "adherence to choice" and 10 measured "adherence to treatment." There was considerable heterogeneity in how adherence was measured, with studies varying in whether they considered baseline choice, follow-up choice, or neither, and whether they presented separate or aggregated adherence measures. No studies measuring "adherence to choice" reported significant differences between the decision aid and comparator, whereas four studies measuring adherence to treatment reported a statistically significant difference between the decision aid and comparator, with three favoring the decision aid arm. CONCLUSIONS: The adherence framework provided insight into important measurement factors. There remains considerable heterogeneity in measures of adherence which makes it difficult to draw conclusions. PMID- 27185075 TI - Serum I-FABP Detects Gluten Responsiveness in Adult Celiac Disease Patients on a Short-Term Gluten Challenge. AB - OBJECTIVES: Response to gluten challenge (GC) is a key feature in diagnostic algorithms and research trials in celiac disease (CD). Currently, autoantibody titers, late responders to GC, and invasive duodenal biopsies are used to evaluate gluten responsiveness. This study investigated the accuracy of serum intestinal-fatty acid binding protein (I-FABP), a marker for intestinal epithelial damage, to predict intestinal damage during GC in patients with CD. METHODS: Twenty adult CD patients in remission underwent a two-week GC with 3 or 7.5 g of gluten daily. Study visits occurred at day -14, 0, 3, 7, 14, and 28. Serum I-FABP, antibodies to tissue transglutaminase (tTG-IgA), deamidated gliadin peptides (IgA-DGP), and anti-actin (AAA-IgA) were assessed at each visit. Villous height to crypt-depth ratio (Vh:Cd) and intraepithelial lymphocyte (IEL) count were evaluated at day -14, 3, and 14. Forty-three CD-serology negative individuals were included to compare serum I-FABP levels in CD patients on a gluten-free diet (GFD) with those in healthy subjects. RESULTS: Serum I-FABP levels increased significantly during a two-week GC. In contrast, the most pronounced autoantibody increase was found at day 28, when patients had already returned to a GFD for two weeks. IgA-AAA titers were only significantly elevated at day 28. I-FABP levels and IEL count correlated at baseline (r=0.458, P=0.042) and at day 14 (r=0.654, P=0.002) of GC. Neither gluten dose nor time on a GFD influenced I-FABP change during GC. CONCLUSIONS: Serum I-FABP levels increased significantly during a two-week GC in adult CD patients and correlated with IEL count. The data suggest that serum I-FABP is an early marker of gluten-induced enteropathy in celiac patients and may be of use in both clinical and research settings. PMID- 27185076 TI - Predictors of Early Failure After Fecal Microbiota Transplantation for the Therapy of Clostridium Difficile Infection: A Multicenter Study. AB - OBJECTIVES: Fecal microbiota transplant (FMT) is a highly efficacious treatment for recurrent or refractory Clostridium difficile infection (CDI); however, 10 20% of patients fail to achieve cure after a single FMT. The aim of this study was to identify risk factors associated with FMT failure and to develop and validate a prediction model for FMT failure. METHODS: Patient characteristics, CDI history, FMT characteristics, and outcomes data for patients treated between 2011 and 2015 at three academic tertiary referral centers were prospectively collected. Early FMT failure was defined as non-response or recurrence of diarrhea associated with positive stool C. difficile toxin or PCR within 1 month of FMT. Late FMT failure was defined as recurrence of diarrhea associated with positive stool C. difficile toxin or PCR between 1 and 3 months of the FMT. Patient data from two centers were used to determine independent predictors of FMT failure and to build a prediction model. A risk index was constructed based on coefficients of final predictors. The patient cohort from the third center was used to validate the prediction model. RESULTS: Of 328 patients in the developmental cohort, 73.5% (N=241) were females with a mean age of 61.4+/-19.3 years; 19.2% (N=63) had inflammatory bowel disease (IBD), and 23.5% (N=77) were immunocompromised. The indication for FMT was recurrent CDI in 87.2% (N=286) and severe or severe-complicated in 12.8% (N=42). FMT was performed as an inpatient in 16.7% (N=54). The stool source was patient-directed donors in 40% (N=130) of cases. The early FMT failure rate was 18.6%, and the late failure rate was 2.7%. In the multivariable analysis, predictors of early FMT failure included severe or severe-complicated CDI (odds ratio (OR) 5.95, 95% confidence interval (CI): 2.26 15.62), inpatient status during FMT (OR 3.78, 95% CI: 1.55-9.24), and previous CDI-related hospitalization (OR 1.43, 95% CI: 1.18-1.75); with each additional hospitalization, the odds of failure increased by 43%. Risk scores ranged from 0 to 13, with 0 indicating low risk, 1-2 indicating moderate risk, and >=3 indicating high risk. In the developmental cohort, early FMT failure rates were 5.6% for low risk, 12.7% for moderate risk, and 41% for high-risk patients. Of 134 patients in the validation cohort, 57% (N=77) were females with a mean age of 66+/-18.1 years; 9.7% (N=13) had IBD, and 17.9% (N=24) were immunocompromised. The early FMT failure rate at 1 month was 19.4%, with an additional 3% failing by 3 months. In the validation cohort, FMT failure rates were 2.1% for low risk, 16.1% for moderate risk, and 35.7% for high risk patients. The area under the receiver operating characteristic curve (AUROC) for FMT failure was 0.81 in the developmental cohort and 0.84 in the validation cohort. CONCLUSIONS: Severe and severe-complicated indication, inpatient status during FMT, and the number of previous CDI-related hospitalizations are strongly associated with early failure of a single FMT for CDI. The novel prediction model has good discriminative power at identifying individuals who are at high risk of failure after FMT therapy and may assist the treating physician in subsequent management plans. PMID- 27185077 TI - Randomized, Placebo-Controlled Trial of Biofeedback for the Treatment of Rumination. AB - OBJECTIVES: We previously demonstrated that rumination is produced by an unperceived, somatic response to food ingestion, and we developed an original biofeedback technique based on electromyography (EMG)-guided control of abdomino thoracic muscular activity. Our aim was to demonstrate the superiority of biofeedback vs. placebo for the treatment of rumination. METHODS: Randomized, placebo-controlled trial performed in a referral center. Consecutive patients who fulfilled the Rome III criteria for rumination (18 women, 6 men; 19-79 years age) were selected and all included in the study; 1 patient assigned to placebo withdrew because of an unrelated accident. Abdomino-thoracic muscle activity after a challenge meal was recorded by EMG. The patients in the biofeedback group were shown the signal and instructed to control muscle activity, whereas the patients in the placebo group were not shown the signal and were given oral simethicone. Each patient underwent 3 sessions over a 10-day period. MAIN OUTCOME: number of rumination events as measured by questionnaires for 10 consecutive days before and after intervention. RESULTS: Patients on biofeedback (n=12) but not on placebo (n=11) effectively learned to reduce intercostal activity (by 51+/-6% vs. 10+/-7% increment on placebo; P<0.001) and anterior wall muscle activity (by 52+/-4% vs. 9+/-2% increment on placebo; P<0.001). Biofeedback treatment resulted in a 74+/-6% reduction in rumination activity (from 29+/-6 before to 7+/-2 daily events after intervention) vs. 1+/-14% on placebo; P=0.001 (from 21+/-2 before to 21+/-4 daily events after intervention). CONCLUSIONS: Rumination can be effectively corrected by biofeedback-guided control of abdomino-thoracic muscular activity. PMID- 27185078 TI - Risks and Predictors of Gastric Adenocarcinoma in Patients with Gastric Intestinal Metaplasia and Dysplasia: A Population-Based Study. AB - OBJECTIVES: Gastric intestinal metaplasia and dysplasia are precursor lesions for adenocarcinoma. The risks of progression to malignancy from these lesions are not well characterized, particularly in the US populations. METHODS: We identified 4,331 Kaiser Permanente Northern California members who were diagnosed with gastric intestinal metaplasia or dysplasia between 1997 and 2006 and followed them through December 2013. The incident rates of gastric adenocarcinoma, relative risks in comparison with the Kaiser Permanente general population, and predictors of progression to malignancy were investigated. RESULTS: Among 4,146 individuals with gastric intestinal metaplasia and 141 with low-grade dysplasia with 24,440 person-years follow-up, 17 and 6 cases of gastric adenocarcinoma were diagnosed, respectively, after 1 year from the index endoscopy. The incidence rate of gastric adenocarcinoma was 0.72/1,000 person-years in patients with intestinal metaplasia, with a relative risk of 2.56 (95% confidence interval (CI) 1.49-4.10) compared with the Kaiser Permanente member population, and 7.7/1,000 person-years for low-grade dysplasia, with a relative risk of 25.6 (95% CI, 9.4 55.7). The median time for gastric intestinal metaplasia to progress to adenocarcinoma was 6.1 years, and for low-grade dysplasia, 2.6 years. Hispanic race/ethnicity and history of dysplasia were associated with significantly higher risk of progression to gastric adenocarcinoma. CONCLUSIONS: Gastric intestinal metaplasia and dysplasia are significant predictors for gastric adenocarcinoma. The low risk for malignancy associated with intestinal metaplasia does not support routine endoscopic surveillance. However, surveillance should be considered in patients at higher risks, including those with suspicious endoscopic features, presence of dysplasia, and Hispanic race/ethnicity. PMID- 27185079 TI - The Efficacy and Tolerability of a Triple Therapy Containing a Potassium Competitive Acid Blocker Compared With a 7-Day PPI-Based Low-Dose Clarithromycin Triple Therapy. AB - OBJECTIVES: This study evaluated the efficacy and tolerability of potassium competitive acid blocker (P-CAB), a new class of gastric acid inhibitory agents, as first-line H. pylori eradication treatment compared with 7-day proton pump inhibitor (PPI)-based triple therapy. METHODS: We retrospectively reviewed the medical records of 661 consecutive patients who received first-line H. pylori eradication treatment between January 2013 and October 2015. Patients who received 7-day P-CAB therapy (vonoprazan 20 mg+amoxicillin 750 mg+clarithromycin 200 mg twice/day; n=181) were compared with those who received 7-day PPI therapy (lansoprazole 30 mg/rabeprazole 20 mg+amoxicillin 750 mg+clarithromycin 200 mg twice/day; n=480) using propensity score matching analysis. The successful eradication and adverse event rates were compared between the two groups. RESULTS: The propensity score matching analysis yielded 175 matched pairs. Adjusted comparisons between the two groups showed a significantly higher eradication rate for the P-CAB than the PPI group in both intention-to-treat (89.1 vs. 70.9%; P<0.001) and per-protocol analyses (91.2 vs. 71.7%; P<0.001). There was no significant difference in the incidence of adverse events between the two therapies except skin rash. No patients discontinued H. pylori eradication treatment because of adverse events. CONCLUSIONS: Seven-day P-CAB based triple therapy was more effective than 7-day PPI-based triple therapy as a first-line H. pylori eradication treatment. Seven-day P-CAB-based triple therapy was generally well-tolerated. PMID- 27185082 TI - Vocational outcome 6-15 years after a traumatic brain injury. AB - PRIMARY OBJECTIVE: To describe vocational outcome 6-15 years after a traumatic brain injury (TBI) among individuals who were productive by working or studying at the time of their TBI and determine the associations with variables related to the time of injury and at follow-up. METHODS AND PROCEDURES: Thirty-four individuals with a mild TBI and 45 with a moderate-to-severe TBI were assessed on average 10 years post-injury. Logistic regression was used to determine the association between their current vocational situation and variables related to the time of injury (gender, age, injury severity and educational level) and at follow-up (time since injury, marital status and overall disability). RESULTS: A total of 67% were productive at follow-up. Age at injury, injury severity and the degree of disability at follow-up were strongly associated with being productive. Younger individuals with milder TBI and less severe disability were significantly more likely to be fully productive. No significant associations were found between productivity and gender, education, time since injury or marital status. CONCLUSIONS: This study indicates that return to productivity in a long-term perspective after a TBI is possible, in particular when the individual is young, has sustained a mild TBI and has a milder form of overall disability. PMID- 27185083 TI - Near-Infrared Upconversion Chemodosimeter for In Vivo Detection of Cu(2+) in Wilson Disease. AB - Near-infrared upconversion chemodosimetry is a promising detection method by virtue of the frequency upconversion technique, which shows very high sensitivity and selectivity for the detection of Cu(2+) ions in vitro and in vivo. This method offers a new opportunity for noninvasive diagnosis of Wilson disease associated with Cu(2+) detection in clinical medicine. PMID- 27185080 TI - Metabolically Healthy Obesity and the Development of Nonalcoholic Fatty Liver Disease. AB - OBJECTIVES: The risk of nonalcoholic fatty liver disease (NAFLD) among obese individuals without obesity-related metabolic abnormalities, a condition referred to as metabolically healthy obese (MHO), is largely unexplored. Therefore, we examined the association between body mass index (BMI) categories and the development of NAFLD in a large cohort of metabolically healthy men and women. METHODS: A cohort study was conducted in 77,425 men and women free of NAFLD and metabolic abnormalities at baseline, who were followed-up annually or biennially for an average of 4.5 years. Being metabolically healthy was defined as not having any metabolic syndrome component and having a homeostasis model assessment of insulin resistance <2.5. The presence of fatty liver was determined using ultrasound. RESULTS: During 348,193.5 person-years of follow-up, 10,340 participants developed NAFLD (incidence rate, 29.7 per 1,000 person-years). The multivariable adjusted hazard ratios (95% confidence intervals) for incident NAFLD comparing overweight and obese with normal-weight participants were 2.15 (2.06-2.26) and 3.55 (3.37-3.74), respectively. In detailed dose-response analyses, increasing baseline BMI showed a strong and approximately linear relationship with the incidence of NAFLD, with no threshold at no risk. This association was present in both men and women, although it was stronger in women (P for interaction <0.001), and it was evident in all clinically relevant subgroups evaluated, including participants with low inflammation status. CONCLUSIONS: In a large cohort of strictly defined metabolically healthy men and women, overweight and obesity were strongly and progressively associated with an increased incidence of NAFLD, suggesting that the obese phenotype per se, regardless of metabolic abnormalities, can increase the risk of NAFLD. PMID- 27185081 TI - Recombinant vesicular stomatitis virus-based dengue-2 vaccine candidate induces humoral response and protects mice against lethal infection. AB - Dengue is the most important arbovirus disease throughout the world and it is responsible for more than 500,000 dengue hemorrhagic cases and 22,000 deaths every year. One vaccine was recently licensed for human use in Brazil, Mexico and Philippines and although at least seven candidates have been in clinical trials the results of the most developed CYD vaccine have demonstrated immunization problems, such as uneven protection and interference between serotypes. We constructed a vaccine candidate based on vesicular stomatitis virus (VSV) expression of pre-membrane (prM) and envelope (E) proteins of dengue-2 virus (DENV-2) and tested it in mice to evaluate immunogenicity and protection against DENV-2 infection. VSV has been successfully used as vaccine vectors for several viruses to induce strong humoral and cellular immune responses. The VSV-DENV-2 recombinant was constructed by inserting the DENV-2 structural proteins into a VSV plasmid DNA for recombinant VSV-DENV-2 recovery. Infectious recombinant VSV viruses were plaque purified and prM and E expression were confirmed by immunofluorescence and radiolabeling of proteins of infected cells. Forty Balb/C mice were inoculated through subcutaneous (s.c.) route with VSV-DENV-2 vaccine in a two doses schedule 15 d apart and 29 d after first inoculation, sera were collected and the mice were challenged with 50 lethal doses (LD50) of a neurovirulent DENV-2. The VSV-DENV-2 induced anti-DENV-2 antibodies and protected animals in the challenge experiment comparable to DENV-2 immunization control group. We conclude that VSV is a promising platform to test as a DENV vaccine and perhaps against others Flaviviridae. PMID- 27185085 TI - Severe and fatal pharmaceutical poisoning in young children in the UK. AB - OBJECTIVE: Accidental poisoning in young children is common, but severe or fatal events are rare. This study was performed to identify the number of such events occurring in the UK and the medications that were most commonly responsible. DESIGN: Analysis of national data sets containing information relating to severe and fatal poisoning in children in the UK. DATA SOURCES: Office of National Statistics mortality data for fatal poisoning; Paediatric Intensive Care Audit Network admissions database and the National Poisons Information Service for severe non-fatal poisoning; Hospital Episode Statistics for admission data for implicated agents. RESULTS: Between 2001 and 2013, there were 28 children aged 4 years and under with a death registered as due to accidental poisoning by a pharmaceutical product in England and Wales. Methadone was the responsible drug in 16 (57%) cases. In the UK, 201 children aged 4 years and under were admitted to paediatric intensive care with pharmaceutical poisoning between 2002 and 2012. The agent(s) responsible was identified in 115 cases, most commonly benzodiazepines (22/115, 19%) and methadone (20/115, 17%). CONCLUSIONS: Methadone is the most common pharmaceutical causing fatal poisoning and a common cause of intensive care unit admissions in young children in the UK. PMID- 27185087 TI - Wrist extension or flexion mobilization orthosis: The dinosaur design. AB - These authors describe how to fabricate an orthotic device to regain wrist range of motion flexion and extension deficits. Using 1 device can offer a more cost effective solution than using 2 separate devices. -Kristin Valdes, OTD, OT, CHT, Practice Forum Editor. PMID- 27185086 TI - Experimental and theoretical approaches for Cd(II) biosorption from aqueous solution using Oryza sativa biomass. AB - Biomass of Oryza sativa (OS) was tested for the removal of Cd(II) ions from synthetic and real wastewater samples. Batch experiments were conducted to investigate the effects of operating parameters on Cd(II) biosorption. Fourier transform infrared spectroscopy, scanning electron microscopy, and energy dispersive x-ray spectroscopy were used to examine the surface characteristics of the Cd(II)-loaded biomass. The maximum removal efficiency of Cd(II) was 89.4% at optimum pH 6.0, biosorbent dose 10.0 g L(-1), initial Cd(II) 50 mg L(-1), and biosorbent particle size 0.5 mm. The applicability of Langmuir and Freundlich isotherms to the sorbent system implied the existence of both monolayer and heterogeneous surface conditions. Kinetic studies revealed that the adsorption process of Cd(II) followed the pseudo-second-order model (r2: 0.99). On the theoretical side, an adaptive neuro-fuzzy inference system (ANFIS) was applied to select the operating parameter that mostly influences the Cd(II) biosorption process. Results from ANFIS indicated that pH was the most influential parameter affecting Cd(II) removal efficiency, indicating that the biomass of OS was strongly pH sensitive. Finally, the biomass was confirmed to adsorb Cd(II) from real wastewater samples with removal efficiency close to 100%. However, feasibility studies of such systems on a large-scale application remain to be investigated. PMID- 27185084 TI - Microfluidic models for adoptive cell-mediated cancer immunotherapies. AB - Current adoptive T cell therapies have shown promising results in clinical trials but need further development as an effective cancer treatment. Here, we discuss how 3D microfluidic tumour models mimicking the tumour microenvironment could help in testing T cell immunotherapies by assessing engineered T cells and identifying combinatorial therapy to improve therapeutic efficacy. We propose that 3D microfluidic systems can be used to screen different patient-specific treatments, thereby reducing the burden of in vivo testing and facilitating the rapid translation of successful T cell cancer immunotherapies to the clinic. PMID- 27185088 TI - Analyzing finger interdependencies during the Purdue Pegboard Test and comparative activities of daily living. AB - STUDY DESIGN: Bench and cross-sectional study. INTRODUCTION: Information obtained from dexterity tests is an important component of a comprehensive examination of the hand. PURPOSE OF THE STUDY: To analyze and compare finger interdependencies during the performance of the Purdue Pegboard Test (PBT) and comparative daily tasks. METHODS: A method based on the optoelectronic kinematic analysis of the precision grip style and on the calculation of cross-correlation coefficients between relevant joint angles, which provided measures of the degree of finger coordination, was conducted on 10 healthy participants performing the PBT and 2 comparative daily living tasks. RESULTS: Daily tasks showed identifiable interdependencies patterns between the metacarpophalangeal joints of the fingers involved in the grip. Tasks related to activities of daily living resulted in significantly higher cross-correlation coefficients across subjects and movements during the formation and manipulation phases of the tasks (0.7-0.9), whereas the release stage produced significantly lower movement correlation values (0.3-0.7). Contrarily, the formation and manipulation stages of the PBT showed low finger correlation across most subjects (0.2-0.6), whereas the release stage resulted in the highest values for all relevant movements (0.65-0.9). DISCUSSION: Interdependencies patterns were consistent for the activities of daily living but differ from the patterns observed from the PBT. CONCLUSIONS: The PBT does not compare well with the whole range of finger movements that account for hand performance during daily tasks. LEVEL OF EVIDENCE: Not applicable. PMID- 27185089 TI - Combination of deep eutectic solvent and ionic liquid to improve biocatalytic reduction of 2-octanone with Acetobacter pasteurianus GIM1.158 cell. AB - The efficient anti-Prelog asymmetric reduction of 2-octanone with Acetobacter pasteurianus GIM1.158 cells was successfully performed in a biphasic system consisting of deep eutectic solvent (DES) and water-immiscible ionic liquid (IL). Various DESs exerted different effects on the synthesis of (R)-2-octanol. Choline chloride/ethylene glycol (ChCl/EG) exhibited good biocompatibility and could moderately increase the cell membrane permeability thus leading to the better results. Adding ChCl/EG increased the optimal substrate concentration from 40 mM to 60 mM and the product e.e. kept above 99.9%. To further improve the reaction efficiency, water-immiscible ILs were introduced to the reaction system and an enhanced substrate concentration (1.5 M) was observed with C4MIM.PF6. Additionally, the cells manifested good operational stability in the reaction system. Thus, the efficient biocatalytic process with ChCl/EG and C4MIM.PF6 was promising for efficient synthesis of (R)-2-octanol. PMID- 27185090 TI - Digestion of cooked meat proteins is slightly affected by age as assessed using the dynamic gastrointestinal TIM model and mass spectrometry. AB - In humans, meat ensures the supply of proteins with high nutritional value and indispensable amino acids. The main goal of the present study was to compare the degradation of meat proteins in adult and elderly digestive conditions. Cooked meat was subjected to in vitro digestion in the dynamic multi-compartmental TIM (TNO gastroIntestinal Model) system. Digestibility and bioaccessibility were determined using nitrogen balance and digestion products were identified using mass spectrometry. The TIM model was adapted according to in vivo data to mimic the specific digestive conditions of elderly people. Meat protein digestibility and bioaccessibility were around 96 and 60% respectively and were not influenced by age (P > 0.05). As much as 800 peptides were identified in the duodenal and jejunal compartments issued from 50 meat proteins with a percentage of coverage varying from 13 to 69%. Six proteins, mainly from the cytosol, were differentially hydrolyzed under the adult and elderly digestive conditions. Pyruvate kinase was the only protein clearly showing a delay in its degradation under elderly digestive conditions. This study provides significant insights into the understanding of meat protein dynamic digestion. Such data will be helpful to design in vivo studies aiming to evaluate dietary strategies that can attenuate muscle mass loss and more generally maintain a better quality of life in the elderly population. PMID- 27185091 TI - Efficacy of Rechallenge of Metastatic Renal Cell Carcinoma Patient With Sunitinib After Prior Resistance to Axitinib: Case Report and Review of the Literature. PMID- 27185097 TI - Magnetization transfer as a potential tool for the early detection of acute graft rejection after lung transplantation in mice. AB - PURPOSE: To investigate the value of magnetization transfer (MT) measurements for assessment of acute rejection (AR) in a murine lung transplantation model. MATERIALS AND METHODS: Thirty mice including 15 C57BL/10 mice serving as donors and 15 C57BL/6 mice as recipients were examined in this study. MT imaging datasets were acquired on a 4.7 Tesla small animal MR scanner using a three dimensional zero echo time sequence with a Gaussian-shaped MT prepulse with 1000 degrees or 3000 degrees flip angle and systematic variation of off-resonance frequencies between 1000 and 15,000 Hz. After image acquisition, the images were qualitatively assessed, magnetization transfer ratio (MTR) values were calculated and lungs were taken for histologic examination including staining with hematoxylin/eosin, Masson's trichrome (collagen), and alpha-smooth muscle (fibroproliferative tissue) staining. RESULTS: Lung transplantation was successfully performed in all 15 mice. All animals showed AR characterized by the presence of interstitial mononuclear cell infiltrates. There were significant differences of MTR in lungs with and without AR (P = 0.007). With a flip angle of 1000 degrees , the largest differences between the MTR of healthy lungs and lungs with AR were observed for an off-resonance frequency of 10,000 Hz (difference MTR 1.80%) and 15,000 Hz (1.91%) and with a flip angle of 3000 degrees at off resonance frequencies of 6000 Hz (1.37%) and 8000 Hz (1.70%). CONCLUSION: MT measurements may provide a tool for the quantitative assessment of AR. J. Magn. Reson. Imaging 2016;44:1091-1098. PMID- 27185098 TI - Just Say No: Stemming the Tide of Antibiotic Overprescription. PMID- 27185102 TI - Actions of activin A, connective tissue growth factor, hepatocyte growth factor and teratocarcinoma-derived growth factor 1 on the development of the bovine preimplantation embryo. AB - The reproductive tract secretes bioactive molecules collectively known as embryokines that can regulate embryonic growth and development. In the present study we tested four growth factors expressed in the endometrium for their ability to modify the development of the bovine embryo to the blastocyst stage and alter the expression of genes found to be upregulated (bone morphogenetic protein 15 (BMP15) and keratin 8, type II (KRT8)) or downregulated (NADH dehydrogenase 1 (ND1) and S100 calcium binding protein A10 (S100A10)) in embryos competent to develop to term. Zygotes were treated at Day 5 with 0.01, 0.1 or 1.0nM growth factor. The highest concentration of activin A increased the percentage of putative zygotes that developed to the blastocyst stage. Connective tissue growth factor (CTGF) increased the number of cells in the inner cell mass (ICM), decreased the trophectoderm:ICM ratio and increased blastocyst expression of KRT8 and ND1. The lowest concentration of hepatocyte growth factor (HGF) reduced the percentage of putative zygotes becoming blastocysts. Teratocarcinoma derived growth factor 1 increased total cell number at 0.01nM and expression of S100A10 at 1.0nM, but otherwise had no effects. Results confirm the prodevelopmental actions of activin A and indicate that CTGF may also function as an embryokine by regulating the number of ICM cells in the blastocyst and altering gene expression. Low concentrations of HGF were inhibitory to development. PMID- 27185100 TI - Improvement of cancellous bone microstructure in patients on teriparatide following alendronate pretreatment. AB - An increase in procollagen type I amino-terminal propeptide (PINP) early after teriparatide initiation was shown to correlate with increased lumbar spine areal BMD and is a good predictor of the anabolic response to teriparatide. Few data exist correlating PINP and bone microstructure, and no data exist in patients on teriparatide following prior potent antiresorptive treatment. This exploratory analysis aimed to investigate the effects of teriparatide on cancellous bone microstructure and correlations of bone markers with microstructure in alendronate-pretreated patients. This was a post hoc analysis of changes in bone markers and three-dimensional indices of bone microstructure in paired iliac crest biopsies from a prospective teriparatide treatment study in postmenopausal women with osteoporosis who were either treatment-naive (TN, n=16) or alendronate pretreated (ALN, n=29) at teriparatide initiation. Teriparatide (20MUg/day) was given for 24months; biopsies were taken at baseline and endpoint, and serum concentrations of PINP and type 1 collagen cross-linked C-telopeptide (betaCTX) were measured at intervals up to 24months. In the TN and ALN groups, respectively, mean (SD) increases in three-dimensional bone volume/tissue volume were 105 (356)% (P=0.039) and 55 (139)% (P<0.005) and trabecular thickness 30.4 (30)% (P<0.001) and 30.8 (53)% (P<0.001). No significant changes were observed in trabecular number or separation. In the ALN patients, 3-month change of neither PINP nor betaCTX correlated with indices of cancellous bone microstructure. However, 12-month changes in biochemical bone markers correlated significantly with improvements in bone volume/tissue volume, r=0.502 (P<0.01) and r=0.378 (P<0.05), trabecular number, r=0.559 (P<0.01) and r=0.515 (P<0.01), and reduction of trabecular separation, r=-0.432 (P<0.05) and r=-0.530 (P<0.01), for PINP and betaCTX, respectively. We conclude that cancellous bone microstructure improved with teriparatide therapy irrespective of prior antiresorptive use. PMID- 27185101 TI - Phosphorescent Differential Sensing of Physiological Phosphates with Lanthanide Ions-Modified Mn-Doped ZnCdS Quantum Dots. AB - Phosphates, both inorganic and organic, play fundamental roles in numerous biological and chemical processes. The biological functions of phosphates connect with each other, analysis of single phosphate-containing biomolecule therefore cannot reveal the exact biological significance of phosphates. Sensor array is therefore the best choice for differentiation analysis of physiological phosphates. Lanthanide ions possess high affinity toward physiological phosphates, while lanthanide ions can also efficiently quench the luminescence of quantum dots (QDs). Taking lanthanide ions as cartridges, here we proposed a sensor array for sensing of physiological phosphates based on lanthanide ions modified Mn-doped ZnCdS phosphorescent QDs in the manner of indicator displacement assay. A series of lanthanide ions were selected as quencher for phosphorescent QDs. Physiological phosphates could subsequently displace the quencher and recover the phosphorescence. Depending on their varied phosphorescence restoration, a sensor array was thus developed. The photophysics of phosphorescence quenching and restoration were studied in detail for better understanding the mechanism of the sensor array. The exact contribution of each sensor element to the sensor array was evaluated. Those sensor elements with little contribution to the differentiation analysis were removed for narrowing the size of the array. The proposed sensor array was successfully explored for probing nucleotide phosphates-involved enzymatic processes and their metabolites, simulated energy charge changes, and analysis of physiological phosphates in biological samples. PMID- 27185103 TI - Rapid characterization of hybridomas producing monoclonal antibodies against platelet beta3 integrin using ELIspot. AB - Generally, B-cell responses against human platelet antigens are assessed by the serological detection of specific platelet antibodies, mostly against beta3 integrin. However, this approach seems to be of low sensitivity, since platelet autoantibodies against alphaIIbbeta3 are detected in only 50% of all patients with immune thrombocytopenia (ITP). In this study, a novel B-cell ELIspot method was established to characterize the specificity of mouse monoclonal antibodies (moabs) against human beta3 integrin. Moabs produced by hybridomas were immobilized on membrane and bound antibodies were visualized as spots using biotinylated recombinant proteins alphaIIbbeta3 or alphavbeta3 and the enzyme labeled streptavidin-substrate system. Three hybridomas, Gi5, Gi16 and AP3, designated previously as anti-alphaIIbbeta3, anti-alphaIIb and anti-beta3, respectively, were investigated. Hybridoma producing moab against CD177 was used as the negative control. Whereas AP3 reacted with alphaIIbbeta3 and alphavbeta3, Gi5 only formed spots with alphaIIbbeta3. Titration analysis showed that the number of spots correlated significantly with the number of seeded cells. Approximately 15 antibody producing hybridoma cells could be identified among 103 nonproducing B-cells. Furthermore, superior correlation with the total number of IgG producing cells was obtained. Analysis of the third hybridoma, Gi16 (anti alphaIIb), showed only few spots with alphaIIbbeta3, indicating that this hybridoma contained different clones (producer and non-producer). Significant increased number of spots could be identified after re-cloning of these clones by limiting dilution method. Our results demonstrate that this B-cell ELIspot assay can be used for the identification of a small number of hybridoma cells producing moabs against beta3 integrin, verification of their monoclonality, productivity and for determining their specificity in the early state of workup steps. In the future, this approach may be useful to define B-cell clones in patients who developed platelet antibodies against different beta3-integrins and to differentiate their diversities. PMID- 27185105 TI - Violence is Rare in Autism: When It Does Occur, Is It Sometimes Extreme? AB - A small body of literature has suggested that, rather than being more likely to engage in offending or violent behavior, individuals with autism spectrum disorder (ASD) may actually have an increased risk of being the victim rather than the perpetrator of violence (Sobsey, Wells, Lucardie, & Mansell, 1995 ). There is no evidence that people with ASD are more violent than those without ASD (Im, 2016). There is nevertheless a small subgroup of individuals with ASD who exhibit violent offending behaviours and our previous work has suggested that other factors, such as adverse childhood experiences, might be important in this subgroup (Allely, Minnis, Thompson, Wilson, & Gillberg, 2014 ). Fitzgerald ( 2015 ) highlights that school shootings and mass killings are not uncommonly carried out by individuals with neurodevelopmental disorders, with frequent evidence of warning indicators. The aim of the present review is to investigate this in more detail using the 73 mass shooting events identified by Mother Jones (motherjones.com) in their database for potential ASD features. There are 73 mass shooting events but there are two events where there is a pair of shooters which meant that 75 mass shooter cases were investigated. This exercise tentatively suggests evidence of ASD in six of 75 included cases (8%) which is about eight times higher when compared to the prevalence of ASD found in the general population worldwide (motherjones.com). The 8% figure for individuals with ASD involved mass killings is a conservative estimate. In addition to the six cases which provide the 8% figure, there were 16 other cases with some indication of ASD. Crucially, ASD may influence, but does not cause, an individual to commit extreme violent acts such as a mass shooting episode. PMID- 27185104 TI - Learning and the transformative potential of citizen science. AB - The number of collaborative initiatives between scientists and volunteers (i.e., citizen science) is increasing across many research fields. The promise of societal transformation together with scientific breakthroughs contributes to the current popularity of citizen science (CS) in the policy domain. We examined the transformative capacity of citizen science in particular learning through environmental CS as conservation tool. We reviewed the CS and social-learning literature and examined 14 conservation projects across Europe that involved collaborative CS. We also developed a template that can be used to explore learning arrangements (i.e., learning events and materials) in CS projects and to explain how the desired outcomes can be achieved through CS learning. We found that recent studies aiming to define CS for analytical purposes often fail to improve the conceptual clarity of CS; CS programs may have transformative potential, especially for the development of individual skills, but such transformation is not necessarily occurring at the organizational and institutional levels; empirical evidence on simple learning outcomes, but the assertion of transformative effects of CS learning is often based on assumptions rather than empirical observation; and it is unanimous that learning in CS is considered important, but in practice it often goes unreported or unevaluated. In conclusion, we point to the need for reliable and transparent measurement of transformative effects for democratization of knowledge production. PMID- 27185106 TI - Short-term pulse rate variability is better characterized by functional near infrared spectroscopy than by photoplethysmography. AB - Pulse rate variability (PRV) can be extracted from functional near-infrared spectroscopy (fNIRS) (PRV(NIRS)) and photoplethysmography (PPG) (PRV(PPG)) signals. The present study compared the accuracy of simultaneously acquired PRV(NIRS) and PRV(PPG), and evaluated their different characterizations of the sympathetic (SNS) and parasympathetic (PSNS) autonomous nervous system activity. Ten healthy subjects were recorded during resting-state (RS) and respiratory challenges in two temperature conditions, i.e., room temperature (23 degrees C) and cold temperature (4 degrees C). PRV(NIRS) was recorded based on fNIRS measurement on the head, whereas PRV(PPG) was determined based on PPG measured at the finger. Accuracy between PRV(NIRS) and PRV(PPG), as assessed by cross covariance and cross-sample entropy, demonstrated a high degree of correlation (r > 0.9), which was significantly reduced by respiration and cold temperature. Characterization of SNS and PSNS using frequency-domain, time-domain, and nonlinear methods showed that PRV(NIRS) provided significantly better information on increasing PSNS activity in response to respiration and cold temperature than PRV(PPG). The findings show that PRV(NIRS) may outperform PRV(PPG) under conditions in which respiration and temperature changes are present, and may, therefore, be advantageous in research and clinical settings, especially if characterization of the autonomous nervous system is desired. PMID- 27185107 TI - Individual differences in the distribution of sperm acrosome-associated 1 proteins among male patients of infertile couples; their possible impact on outcomes of conventional in vitro fertilization. AB - The aims of this study were to show the existence of individual differences in the distribution of sperm acrosome-associated 1 (SPACA1) among male patients of infertile couples and to examine their possible impact on the outcomes of conventional in vitro fertilization (IVF). The spermatozoa were collected from male patients of infertile couples, washed by centrifugation, collected by the swim-up method, and then used for clinical treatments of conventional IVF. The surplus sperm samples were fixed and stained with an anti-SPACA1 polyclonal antibody for the immunocytochemistry. In the clinical IVF treatments, fertilization rates and blastocyst development rates were evaluated. The immunocytochemical observations revealed that SPACA1 were localized definitely in the acrosomal equatorial segment and variedly in the acrosomal principal segment. Specifically, the detection patterns of SPACA1 in the acrosomal principal segment could be classified into three categories: (A) strong, (B) intermediate or faint, and (C) almost no immunofluorescence. The SPACA1 indexes were largely different among male patients with the wide range from 13 to 199 points. The SPACA1 indexes were significantly correlated with developmental rates of embryos to blastocysts (r = 0.829, P = 0.00162), although they were barely associated with fertilization rates at 19 h after insemination (r = 0.289, P = 0.389). These results suggest that the distribution of SPACA1 in sperm affects the outcomes of conventional IVF. In conclusion, this study provides initial data to promote large-scale clinical investigation to demonstrate that the SPACA1 indexes are valid as molecular biomarkers that can predict the effectiveness of conventional IVF of infertile couples. PMID- 27185108 TI - Multivalent ligand mimetics of LecA from P. aeruginosa: synthesis and NMR studies. AB - Molecular recognition of glycans plays an important role in glycomic and glycobiology studies. For example, pathogens have a number of different types of lectin for targeting host sugars. In bacteria, lectins exist sometimes as domains of bacterial toxins and exploit adhesion to glycoconjugates as a means of entering host cells. Herein, we describe the synthesis of three glycodendrons with the aim to dissect the fine structural details involved in the multivalent carbohydrate-protein interactions. LecA, from the pathogen Pseudomonas aeruginosa, has been used to characterize galactose dendrons interaction using one of the most widespread NMR technique for the elucidation of receptor-ligand binding in solution, the saturation transfer difference (STD) NMR. Furthermore, the effective hydrodynamic radius of each dendrimer recognized by LecA was estimated from the diffusion coefficients determined by pulsed-field-gradient stimulated echo (PFG-STE) NMR experiments. PMID- 27185109 TI - Modified pineapple peel cellulose hydrogels embedded with sepia ink for effective removal of methylene blue. AB - Novel composite hydrogels based on pineapple peel cellulose and sepia ink were synthesized by homogeneous acetylation of cellulose in ionic liquid 1-butyl-3 methylimidazolium chloride. The structure and morphology of the prepared hydrogels were characterized by Fourier transform infrared spectroscopy, field emission scanning electron microscope, X-ray diffraction, thermogravimetry and differential scanning calorimetry. The effects of acetylation time, acetylation temperature, molar ratio of acetic anhydride/anhydroglucose unit and the additive amount of sepia ink on methylene blue adsorption capacity of the hydrogels embedded with sepia ink were also investigated. Methylene blue adsorption of the hydrogels followed pseudo-second-order kinetic model and sepia ink improved adsorption capacity significantly. The adsorption capacity at equilibrium was increased from 53.72 to 138.25mg/g when the additive amount of sepia ink of the hydrogels was 10%. PMID- 27185110 TI - Characterisation of microcrystalline cellulose from oil palm fibres for food applications. AB - Microcrystalline cellulose (MCC) extracted from empty fruit bunches (EFB), stalk and spikelet were characterised through physicochemical and microstructure analyses. Raw stalk fibres yielded the highest cellulose content (42.43%), followed by EFB (32.33%) and spikelet (18.83%). Likewise, lowest lignin and residual oil content was reported in raw stalk fibres compared to EFB and spikelet. SEM revealed significant changes on fibres' surface morphology throughout the extraction process. FTIR analysis showed that main characteristic peaks of hemicellulose and lignin was absent on the extracted MCC. The crystallinity index for MCC extracted from EFB (82.5%), stalk (82.2%) and spikelet (86.5%) was comparable to commercial MCC (81.9%). Results suggested stalk fibres is more preferable for the production of MCC compared to EFB and spikelet. Further rheological studies showed viscoelastic behaviour with no significant differences between commercial and stalk-based MCC, while modelling work showed ability to simulate complex deformation of the MCC-hydrogel/food mixture during processing/handling stage. PMID- 27185111 TI - Preparation of succinylated cellulose membranes for functionalization purposes. AB - The anhydroglucose chains of cellulose possess hydroxyls that facilitate different chemical modification strategies to expand on, or provide new applications for membranes produced by the bacteria Gluconacetobacter xylinus. Conjugation with biomolecules such as proteins, especially by the amine groups, is of great value and interest for the production of biomaterial derivatives from bacterial cellulose. To assist in these modifications, cellulose was succinylated in order to prevent steric hindrance and to create an attachment point for conjugation. Bacterial cellulose membranes were first treated in dichloromethane and reacted with succinic anhydride through a series of conditions. The membrane structure remained intact after these first processes and the product was confirmed by Infra-Red spectroscopy and solid state nuclear magnetic resonance and characterized by X-ray diffraction, thermogravimetry and atomic force microscopy. Hydrolyzed collagen was used as a model protein of interest to be conjugated to these membranes, which furnished a biomaterial functionalized over its surface. PMID- 27185112 TI - A new photoelectric ink based on nanocellulose/CdS quantum dots for screen printing. AB - CdS quantum dots with excellent photoelectrical properties embedded in nanocellulose could be exploited for use in photoelectrical ink. In this work, nanocellulose/CdS quantum dot composites were fabricated by controlling the carboxylate content of the nanocellulose and the molar ratio of Cd(2+)/-COOH. New photoelectric inks were prepared based on the composites, in which the CdS quantum dots acted as the pigment and the nanocellulose as the binder. The results of the photocurrent of the composites showed that the photocurrent could be tailored by the carboxylate content and the molar ratio of Cd(2+)/-COOH. And the photocurrent could be as high as 2MUA. The surface tension of the photoelectric ink was 27.80+/-0.03mN/m and its viscosity was 30.3mPas. The photoelectric ink was stable with excellent fluidity and rheology, it could therefore be applied to screen-printing and three-dimensional (3D) printing. PMID- 27185113 TI - Interaction between kappa- and iota-carrageenan and anthocyanins from Vaccinium myrtillus. AB - Anthocyanins (ATCs) from the Vaccinium myrtillus water extract have been incorporated into the kappa-carrageenan (kappa-CARG) or iota-carrageenan (iota CARG) during complexation in dilute solutions or adsorption onto the microgranules of kappa-CARG or iota-CARG cross-linked with epichlorohydrin. At the optimal weight ratio of CARG to ATC at 0.4:1 and the total ATCs and CARG concentration<=0.07g/L, stable dispersions of the kappa-CARG/ATCs or iota CARG/ATCs complex nanosize particles were obtained. The Langmuir, Freundlich and Dubinin-Radushkevich adsorption models have been used to describe the equilibrium adsorption of ATCs on cross-linked CARG. The introduction of ATCs into CARG and cross-linked CARG was confirmed by FT-IR spectroscopy. The data of the HPLC analysis showed that during adsorption on cross-linked iota-CARG microgranules ATCs are isolated from the crude water extract of wild bilberries, whereas other phenolics remain in the adsorption solution. After desorption from cross-linked CARG/ATC into different media the sufficiently pure and stable solutions of ATCs were obtained. PMID- 27185114 TI - Freeze-thaw induced gelation of alginates. AB - Adding divalent ions or lowering pH below the pKa values of alginate monomers are common ways in preparing alginate gels. Herein a new way of preparing alginate gels using freeze-thaw technique is described. Solvent crystallization during freezing drove the polymers to associate into certain structures that became the junction zones of hydrogels after thawing. It enabled the preparation of alginate gels at pH 4.0 and 3.5, two pH at which the gel could not be formed previously. At pH 3.0 where alginate gel could be formed initially, applying freeze-thaw treatment increased the gel storage modulus almost 100 times. The formation of hydrogels and the resulting gel properties, such as dynamic moduli and gel syneresis were influenced by the pH values, number of freeze-thaw cycles, alginate concentrations, and ionic strengths. The obtained hydrogels were soft and demonstrated a melting behavior upon storage, which may find novel applications in the biomedical industry. PMID- 27185115 TI - Single molecule investigation of the onset and minimum size of the calcium mediated junction zone in alginate. AB - One of the principal roles of alginate, both natively and in commercial applications, is gelation via Ca(2+)-mediated crosslinks between blocks of guluronic acid. In this work, single molecule measurements were carried out between well-characterised series of nearly monodisperse guluronic acid blocks ('oligoGs') using dynamic force spectroscopy. The measurements provide evidence that for interaction times on the order of tens of milliseconds the maximum crosslink strength is achieved by pairs of oligoGs long enough to allow the coordination of 4Ca(2+) ions, with both shorter and longer oligomers forming weaker links. Extending the interaction time from tens to hundreds of milliseconds allows longer oligoGs to achieve much stronger crosslinks but does not change the strength of individual links between shorter oligoGs. These results are considered in light of extant models for the onset of cooperative crosslinking in polyelectrolytes and an anisotropic distribution of oligoGs on interacting surfaces and provide a timescale for the formation and relaxation of alginate gels at the single crosslink level. PMID- 27185116 TI - The linear structure of beta-glucan from baker's yeast and its activation of macrophage-like RAW264.7 cells. AB - Yeast beta-glucan has many formulations with different chemical structures, water solubility and purity. In particular, the purity of beta-glucan in these formulations is variable and relatively low, contributing to different data on its biological activity. In this study, the major polysaccharide component in the crude Baker's yeast polysaccharides coded as BBG with high purity of 99% was obtained, and its chemical structure was determined to be a linear beta-(1,3) glucan. It was found that BBG interacted with complement receptor 3 (CR3) and toll-like receptor 2 (TLR2) on the surface of macrophage-like RAW264.7 cells, and initiated activation of RAW264.7 cells characterized by significant production of tumor necrosis factor-alpha (TNF-alpha) and monocyte chemoattractant protein 1 (MCP-1). Additionally, activation of the nuclear factor kappaB p65 (NF-kappaB p65), c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) induced by BBG, were also observed, further confirming the stimulation of RAW264.7 cells by BBG. All these findings provided important scientific evidences for better understanding the molecular mechanism of action for the linear beta (1,3)-glucan in cells. PMID- 27185118 TI - Effect of starch on the mechanical and in vitro properties of collagen hydroxyapatite sponges for applications in dentistry. AB - This study sought to improve the mechanical and blood-absorbing properties of collagen sponges, while keeping them compressible, by incorporating blended hydroxyapatite (HA)-starch. Results were compared with CollaPlug((r)) (pure collagen). The elastic modulus increased from 1.5+/-0.2kPa for CollaPlug((r)) to 49+/-8kPa for sponges with composition 1:4:10 (collagen:HA:starch, by weight). The modified microstructure and surface area provided by the starch granules on the sponges improved cell viability. Sponges with composition 1:4:10 maintained their blood-clotting capability with almost no change from 5 to 15min after contact with blood, while CollaPlug((r)) diminished to about half its capacity to absorb blood and form clots. Incorporation of HA-starch into the sponges with composition of 1:4:10, increased the elastic modulus of the collagen-HA sponges, making them more structurally robust. The viability of cells and the blood clotting capability increased with starch incorporation. PMID- 27185117 TI - Nanofibrillated cellulose from tobacco industry wastes. AB - Tobacco stems waste underwent steam explosion pulping for nanofibrillated cellulose (NFC) production. In order to obtain NFC hydrogels, the pulp obtained by steam explosion was bleached and refined in a grinder employing specific energy of up to 5067kWh/t. Eucalyptus kraft pulp was processed under the same conditions to produce NFC hydrogels, later used in order to compare with NFC hydrogels from tobacco stems waste. According to statistical analysis, the optimum tobacco stems pulping condition was obtained with a severity index of log3.0 and active alkali of 16.25%. These conditions allowed obtaining a bleached pulp with Schopper Riegler degree of 46. Electronic microscopy with field emission showed a higher presence of nanofibers in the tobacco stems pulp than in commercial eucalyptus kraft pulp, both after refining. Thermal analysis indicated that tobacco stems pulp degrade at lower temperatures than eucalyptus kraft pulp. FTIR analysis did not indicate chemical bonding differences between the two pulps. PMID- 27185119 TI - Anti-diabetic polysaccharides from natural sources: A review. AB - Diabetes mellitus (DM) is a metabolic disease attracted worldwide concerns, which severely impairs peoples' quality of life and is attributed to several life threatening complications, including atherosclerosis, nephropathy and retinopathy. The current therapies for DM include mainly oral anti-diabetic drugs and insulin. However, continuous use of these causes insulin resistance and side effects, and the demand of effective, nontoxic and affordable drugs for DM patients is eager. Several previous studies have shown that non-toxic biological macromolecules, mainly polysaccharides, possess prominent efficacies on DM. Based on these encouraging observations, a great deal of efforts have been focused on discovering anti-diabetic polysaccharides for the development of effective therapeutics for DM. This review focuses on the advancements in the anti-diabetic efficacy of various natural polysaccharides and polysaccharide complexes from 2010 to 2015. PMID- 27185120 TI - Reactive electrospinning of composite nanofibers of carboxymethyl chitosan cross linked by alginate dialdehyde with the aid of polyethylene oxide. AB - We have prepared carboxymethyl chitosan-alginate dialdehyde (CMCS-ADA) nanofibers via a reactive electrospinning process with the aid of polyethylene oxide (PEO). The presence of PEO delayed the gelation of CMCS and ADA, thus providing ease of use to adjust the mixing of CMCS-PEO and ADA-PEO blended solution. The mixed solution can be adjusted to come out from the needle before the gel formation or when the gel was just about to form. Defect-free CMCS-ADA-PEO nanofibers with average diameters ranging from 100nm to 900nm were obtained using water as a solvent. The in situ cross-linked CMCS-ADA nanofibers were then obtained following the extraction of water-soluble PEO. After immersion in phosphate buffered saline (PBS) at a pH of 7.4 for up to 15days, the as-spun CMCS-ADA-PEO composite nanofibers maintained structural integrity, confirming the success of the crosslinking. The PEO-extracted CMCS-ADA nanofibers promoted the adhesion, proliferation and alkaline phosphatase activity of bone marrow stromal cells. PMID- 27185121 TI - Development of polyamide-6,6/chitosan electrospun hybrid nanofibrous scaffolds for tissue engineering application. AB - The development of biofunctional and bioactive hybrid polymeric scaffolds seek to mitigate the current challenges in the emerging field of tissue engineering. In this paper, we report the fabrication of a biomimetic and biocompatible nanofibrous scaffolds of polyamide-6,6 (PA-6,6) blended with biopolymer chitosan via one step co-electrospinning technique. Different weight percentage of chitosan 10wt%, 15wt%, and 20wt% were blended with PA-6,6, respectively. The nanocomposite electrospun scaffolds mats enabled to provide the osteophilic environment for cells growth and biomineralization. The morphological and physiochemical properties of the resulted scaffolds were studied using field emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), and Fourier transform-infrared (FT-IR) spectroscopy. The improvement in hydrophilicity and mechanical strength of the bio-nanocomposite mesh with 20wt% chitosan embedded, was the desired avenue for adhesion, proliferation and maturation of osteoblast cells as compared to other sample groups and pure PA-6,6 fibrous mat. The biomineralization of the nanocomposite electrospun mats also showed higher ability to nucleate bioactive calcium phosphate (Ca/P) nanoparticles comparing to pristine PA-6,6. Furthermore, the biomimetic nature of scaffolds exhibited the cells viability and regeneration of pre-osteoblast (MC3T3 E1) cells which were assessed via in vitro cell culture test. Collectively, the results suggested that the optimized 20wt% of chitosan supplemented hybrid electrospun fibrous scaffold has significant effect in biomedical field to create osteogenic capabilities for tissue engineering. PMID- 27185123 TI - Structure of clusters and building blocks in amylopectin from African rice accessions. AB - Enzymatic hydrolysis in combination with gel-permeation and anion-exchange chromatography techniques were employed to characterise the composition of clusters and building blocks of amylopectin from two African rice (Oryza glaberrima) accessions-IRGC 103759 and TOG 12440. The samples were compared with one Asian rice (Oryza sativa) sample (cv WITA 4) and one O. sativa*O. glaberrima cross (NERICA 4). The average DP of clusters from the African rice accessions (ARAs) was marginally larger (DP=83) than in WITA 4 (DP=81). However, regarding average number of chains, clusters from the ARAs represented both the smallest and largest clusters. Overall, the result suggested that the structure of clusters in TOG 12440 was dense with short chains and high degree of branching, whereas the situation was the opposite in NERICA 4. IRGC 103759 and WITA 4 possessed clusters with intermediate characteristics. The commonest type of building blocks in all samples was group 2 (single branched dextrins) representing 40.3-49.4% of the blocks, while groups 3-6 were found in successively lower numbers. The average number of building blocks in the clusters was significantly larger in NERICA 4 (5.8) and WITA 4 (5.7) than in IRGC 103759 and TOG 12440 (5.1 and 5.3, respectively). PMID- 27185122 TI - Chitosan/poly(vinyl alcohol)/bovine bone powder biocomposites: A potential biomaterial for the treatment of atopic dermatitis-like skin lesions. AB - Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects a large percent of the worlds population. This long-lasting skin disease has been treated by different approaches according to its causative agent and severity. Nonetheless, the use of advanced biomaterials to treat AD is poorly explored. The present study assessed the protective effectiveness of biocomposites films based on chitosan (Cs), poly(vinyl alcohol) (PVA) and bovine bone powder (BBP) on AD like skin lesions. These original biocomposites were fully characterized and in vivo biological assays concerning the AD treatment were performed using a mouse model induced by 2,4-dinitrochlorobenzene (DNCB). The dorsal skin and ear of Balb/c female mice were challenging cutaneously with DNCB. Our findings demonstrate BBP-based biocomposite attenuated and treated considerably the DNCB induced skin lesions in an AD-like model. In this sense, this study suggests that this original biocomposite may be applied as an active biomaterial for AD treatment. PMID- 27185124 TI - Chitosan-starch beads prepared by ionotropic gelation as potential matrices for controlled release of fertilizers. AB - The present study examines the agrochemical application of macrospheres prepared with chitosan and chitosan-starch blends by an easy dripping technique, using a sodium tripolyphosphate aqueous solution as the crosslinking agent. These biopolymers form hydrogels that could be a viable alternative method to obtain controlled-release fertilizers (CRFs). Three different concentrations (ranging from 20 to 100wt/wt% of chitosan) and two crosslinking times (2 or 4h) were used. The resulting polymeric matrices were examined by scanning electron microscopy coupled with energy dispersive X-ray, X-ray diffraction, Fourier transform infrared spectroscopy, solid-state nuclear magnetic resonance, thermogravimetric analysis and differential scanning calorimetry. Ionotropic gelation and neutralization induced the formation of the macrospheres. The crosslinking time and the composition of the polymeric hydrogel controlled the crosslinking degree, the swelling behavior and the fertilizer loading capability. Potassium nitrate loaded beads were shown to be useful as a controlled-release fertilizer. After 14days of continuous release into distilled water, the cumulative concentration in the release medium reached between 70 and 93% of the initially loaded salt, depending on the matrix used. The prepared beads showed properties that make them suitable for use in the agrochemical industry as CRFs. PMID- 27185126 TI - Dye adsorption and bactericidal properties of TiO2/chitosan coating layer. AB - A new kind of titanium oxide dispersed in chitosan (TiO2/CS) nanocomposite adsorbent was prepared and adhered to high surface area substrate, cellulose microfibers mat (CMM). CS-CMM and TiO2/CS-CMM were used for the thymol violet (TV) dye removal from wastewater. Characterization of materials was carried out by X-ray diffraction, scanning electron microscope and energy dispersive X-ray spectroscopy. The adsorption properties of both the CS-CMM and TiO2/CS-CMM were investigated as a function of adsorbent dosage, solution pH, and contact time. It was revealed that the composites pretreated in the solution with higher pH value exhibited larger adsorption capacities. Kinetic studies showed that the composites could adsorb TV dye rapidly and reached the equilibrium in 90min. The adsorption process followed pseudo-second order kinetics and involved particle diffusion mechanism. The calculated maximum adsorption capacities of CS-CMM and TiO2/CS-CMM were 84.32 and 97.51mgg(-1), respectively. Compare to CS, the TiO2/CS nanocomposite coated CMM showed higher antibacterial characteristics as tested against Escherichia coli. PMID- 27185125 TI - Application of ethyl cellulose, microcrystalline cellulose and octadecanol for wax based floating solid dispersion pellets. AB - The present study aimed to develop and optimize the wax based floating sustained release dispersion pellets for a weakly acidic hydrophilic drug protocatechuic acid to achieve prolonged gastric residence time and improved bioavailability. This low-density drug delivery system consisted of octadecanol/microcrystalline cellulose mixture matrix pellet cores prepared by extrusion-spheronization technique, coated with drug/ethyl cellulose 100cp solid dispersion using single step fluid-bed coating method. The formulation-optimized pellets could maintain excellent floating state without lag time and sustain the drug release efficiently for 12h based on non-Fickian transport mechanism. Observed by SEM, the optimized pellet was the dispersion-layered spherical structure containing a compact inner core. DSC, XRD and FTIR analysis revealed drug was uniformly dispersed in the amorphous molecule form and had no significant physicochemical interactions with the polymer dispersion carrier. The stability study of the resultant pellets further proved the rationality and integrity of the developed formulation. PMID- 27185128 TI - Determination of the glass transition temperature of cyclodextrin polymers. AB - The aim of this work was to determine the main physical characteristics of beta cyclodextrin polymers, well known for improving complexation capacities and providing enhanced and sustained release of a large panel of drugs. Two polymers were investigated: a polymer of beta-cyclodextrin (polybeta-CD) and a polymer of partially methylated (DS=0.57) beta-cyclodextrin (polyMe-beta-CD). The physical characterizations were performed by powder X-ray diffraction and differential scanning calorimetry. The results indicate that these polymers are amorphous and that their glass transition is located above the thermal degradation point of the materials preventing their direct observation and thus their full characterization. We could however estimate the virtual glass transition temperatures by mixing the polymers with different plasticizers (trehalose and mannitol) which decreases Tg sufficiently to make the glass transition observable. Extrapolation to zero plasticizer concentration then yield the following Tg values: Tg (polyMe-beta-CD)=317 degrees C+/-5 degrees C and Tg (polybeta-CD)=418 degrees C+/-6 degrees C. PMID- 27185127 TI - Bathroom greywater recycling using polyelectrolyte-complex bilayer membrane: Advanced study of membrane structure and treatment efficiency. AB - Polyelectrolyte-complex bilayer membrane (PCBM) was fabricated using biodegradable chitosan and alginate polymers for subsequent application in the treatment of bathroom greywater. In this study, the properties of PCBMs were studied and it was found that the formation of polyelectrolyte network reduced the molecular weight cut-off (MWCO) from 242kDa in chitosan membrane to 2.71kDa in PCBM. The decrease in MWCO of PCBM results in better greywater treatment efficiency, subsequently demonstrated in a greywater filtration study where treated greywater effluent met the household reclaimed water standard of <2 NTU turbidity and <30ppm total suspended solids (TSS). In addition, a further 20% improvement in chemical oxygen demand (COD) removal was achieved as compared to a single layer chitosan membrane. Results from this study show that the biodegradable PCBM is a potential membrane material in producing clean treated greywater for non-potable applications. PMID- 27185129 TI - Elucidation of aqueous interactions between fish gelatin and sodium alginate. AB - The interactions between fish gelatin (FG) and sodium alginate (AL) in aqueous solutions were investigated at 25 degrees C by turbidimetric acid titration, zeta potentiometry, dynamic light scattering, methylene blue spectrophotometry, confocal microscopy, and three types of state diagram. FG formed solid-state insoluble complexes, i.e., precipitates, with AL, mainly by electrostatic attractions; the complex formation was significantly influenced by pH, FG-to-AL weight ratio, total biopolymer concentration (CT), and ionic strength. The insoluble complexes formed below a boundary pH (pHphi1) underwent continuous aggregation during acid titration, until immediate visible precipitation occurred at another boundary pH (pHp). The formation and aggregation of insoluble complexes were facilitated by increasing CT or adding small amounts of NaCl, but were greatly suppressed in the presence of high NaCl concentration. The insoluble complexes were formed reversibly depending on pH and transformed to a coupled gel network after 24h incubation, depending on pH, CT, and ionic strength. PMID- 27185130 TI - Hydrogen peroxide generation by the Weissberger biogenic oxidative system during hyaluronan degradation. AB - By applying the enzyme catalase, our study on hyaluronan degradation confirms the generation of hydrogen peroxide using the Weissberger biogenic oxidative system (WBOS), which is composed of ascorbate and cupric ions. Dynamic viscosities of hyaluronan (HA) solutions influenced by WBOS in the absence and presence of catalase were analysed by rotational viscometry. Molar masses of HAs were determined by size-exclusion chromatography with multi-angle laser-light scattering. Our results show that catalase dose-dependently inhibited the degradation of HA macromolecules, which presumably confirms the generation of H2O2 in the reaction system. This has implications in range of biomedical applications such as arthritic joint treatment, tissue engineering, ocular and cosmetic surgery. PMID- 27185131 TI - Photocatalytic activity and antimicrobial properties of paper sheets modified with TiO2/Sodium alginate nanocomposites. AB - Photocatalytic paper sheets were prepared by addition of different ratios of TiO2/Sodium alginate (TSA) nanocomposite. The modified paper sheets were characterized by XRD, TGA. Their morphology was studied by scanning electron microscope (SEM) and energy dispersive X-ray (EDX). Photocatalytic activity of modified paper has been studied by analysis of chemical oxygen demand (COD) of waste-water. The results confirmed the mineralization of the waste-water and enhanced removal of chemical oxygen demand (COD) by increasing the amount of photocatalyst in the paper. Moreover, the results also confirmed that presence of sodium alginate as biopolymer increased adhesion of nanoparticles to paper fibers and reduced the harmful effect of the photocatalyst on them. The paper sheets containing 7% as well as 15% TSA showed high photocatalytic activity and anti bacterial effect against Salmonella typhimurium higher than standard antibiotic beside other microorganisms such as Candida albicans. The maximum antimicrobial effect was found in case of specimen loaded with 15% TSA. Moreover, it was found that by adding 20% TSA to the paper matrix, the properties of the paper composite collapse. The obtained results confirm the possible utilization of the modified paper in both hygienic and food packaging applications. PMID- 27185133 TI - Non toxic, antibacterial, biodegradable hydrogels with pH-stimuli sensitivity: Investigation of swelling parameters. AB - In this work, a series of pH-sensitive hydrogels were synthesized from Sodium alginate (SA), Ethylene glycol (EG) and Acrylic acid (AA). Biodegradability of hydrogel was tested against soil burial test for 35days and in vitro phosphate buffer solution test for 10days respectively. Degradation of the sample might be due to the breakdown of ester linkage and hydrophilic pendant functionality present in hydrogel. The progression of biodegradation was examined by Scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FT-IR). Detailed swelling parameters such as swelling equilibrium Seq (%) at various pH, biological fluids (distilled water (DW), physiological saline 0.89% NaCl (PS), iso-osmotic phosphate buffer at pH 7.4 (PB)) and equilibrium water content (EWC) have also been investigated, which revealed that dynamic compassion of hydrogels. The hydrogel has shown strong antibacterial activity against Escherichia coli (gram negative) and Staphylococcus aureus (gram positive) bacteria's. Cytotoxic assays, using MTT Assay in 3T3 fibroblast Cell line was performed. At 10MUg/ml, cell viability was in the range of 92-94%. However, the cell viability (%) decreases with increasing concentration of sample. The synergistic effect of biodegradable hydrogels possessing excellent swelling properties, high water content, biocompatibility and wound healing tendency using in vivo test can be made as suitable candidate for biomedical applications. In vivo wound healing studies conducted on a Wister albino rat model of incision wound performed for 9days. The results revealed that more accelerated wound healing have been observed even in shorter duration. Thus, the synthesized hydrogel with great pH responsiveness and excellent drug delivery may have a great opening for biomedical applications. PMID- 27185132 TI - Antibacterial activity and mechanism of chitosan with ultra high molecular weight. AB - Chitosan with different degree of deacetylation (DD) and ultra high molecular weight (MW >10(6)) was prepared from beta-chitin by mild deacetylation. The effects of DD of chitosan and pH value of its solution/suspension on its antibacterial activity were investigated. The results showed that the optimal pH value was 6.0 for the highest bactericidal activity. The antibacterial activity against Escherichia coli and Staphylococcus aureus of chitosan solution at pH 6.0 enhanced as the DD of chitosan increased. Same as chitosan with low MW, the antibacterial activity of chitosan with high MW in acidic solution was also due to the amino protonation and subsequently cationic formation. Its ultra long molecular chain was propitious to coat and bind the E. coli and S. aureus, and highly enhanced its antibacterial activity. E. coli and S. aureus were at first restrained and then killed by chitosan and the cells were ruptured and decomposed gradually. PMID- 27185134 TI - Rheological and microstructural properties of porcine gastric digesta and diets containing pectin or mango powder. AB - Hydrated polysaccharides and their assemblies are known to modulate gastric emptying rate due to their capacity to change the structural and rheological properties of gastric contents (digesta). In the present study, we investigated the rheological and microstructural properties of gastric digesta from pigs fed with diets incorporating mango powder or pectin, and compared results with those from hydrated diets of the same water content, in order to investigate the origins for rheological changes in the pig stomach. All of the hydrated diets and gastric digesta were particle-dominated suspensions, generally showing weak gel or more solid-like behavior with the storage modulus (G') always greater than loss modulus (G") under small deformation oscillatory measurements, and with small deformation viscosity greater than steady shear viscosity (i.e. non-Cox Merz superposition). Although significant rheological differences were observed between the hydrated diets, rheological parameters for gastric digesta were similar for all diets, indicative of a rheological homeostasis in the pig stomach. Whilst the addition of gastric mucin (20mg/mL) to control and mango diets altered the rheology to match the gastric digesta rheology, the effect of mucin on the pectin-containing diet was negligible. The viscous effect of pectin also hindered the action of alpha amylase as observed from relatively less damaged starch granules in pectin digesta compared to mango and control digesta. Based on the experimental findings that the rheology of gastric digesta differs from hydrated diets of the same water content, the current study revealed composition-dependent complex behavior of gastric digesta in vivo, suggesting that the rheology of food products or ingredients may not necessarily reflect the rheological effect when ingested. PMID- 27185135 TI - Tuning of cellulose fibres' structure and surface topography: Influence of swelling and various drying procedures. AB - Presented study deals with the pre-treatment of cellulose fibres with the aim to activate their surface and to enlarge their pore system, leading to an enhancement of fibres' affinity for subsequent functionalization processes. Swelling of fibres in aqueous solutions of sodium hydroxide opens their fibrillar structure, while freezing and freeze-drying retain this enlargement of the pore system, in contrast with conventional air or elevated temperature drying. Effect of different pre-treatment procedures on fibres' supramolecular structure, enlargement of their pore system, surface topography, zeta potential and mechanical properties was investigated. Degree of enhancement of the pore system depends on the concentration of sodium hydroxide and type of freezing; higher alkali concentrations are more effective, but at the cost of extensive deterioration of mechanical properties. Swelling of fibres in lower concentrations of NaOH, in combination with freeze drying, offers an acceptable compromise between enhancement of the fibres' pore system, changes in surface potential and tensile properties of treated fibres. Design of a suitable regime of swelling and drying of cellulose fibres results in an effective procedure for controlled tuning of their surface topography in combination with an increase of the available internal surface area and pore volume. PMID- 27185136 TI - Cyclodextrin type dependent host-guest interaction mode with phthalocyanine and their influence on photodynamic activity to cancer. AB - Three host-guest complexes of phthalocyanines (Pc) with alpha-, beta- or gamma cyclodextrins (CDs) were prepared and their interaction modes, reactive oxygen species (ROSs) generation ability and in vitro anticancer activities were studied and compared. After forming complex with CD, the aggregation degree of Pc was greatly decreased and the water solubility and photodynamic activity was sharply increased. Computer modeling results indicated that the interaction modes between Pc and CDs were varied with different kinds of CD. Especially, the complex of Pc and beta-CD has superior stability, ROSs generation ability, and anticancer activity to other complexes. PMID- 27185137 TI - Preparation of biodegradable xanthan-glycerol hydrogel, foam, film, aerogel and xerogel at room temperature. AB - Polymers, hence hydrogels, pollute waters and soils accelerating environmental degradation. Environmentally benign hydrogels were made in water from biodegradable xanthan (X) and glycerol (G) at 22.5+/-2.5 degrees C. Molar ratio [G]/[X]<3.0 was used to maximize crosslinking by mono-glycerol instead by poly glycerol. XG-hydrogels were transformed into: XG-foams, XG-films, and XG-aerogel. Anionic character of XG-materials changes with changing [G]/[X] ratio. XG-films made from XG-hydrogels absorb up to 40 times more water than XG-films made from XG-foams. The films made from XG-foams and HCl do not dissolve in water during 48h. Making XG-materials is a no-waste process which decreases pollution, eliminates waste disposal costs, and minimizes energy expenses. XG-materials are suitable for both industrial and environmental applications including slow release and concentration of cations. XG-materials, made of xanthan, microbial polysaccharide, could also be used in applications targeting populations that do not consume meat or meat based products. PMID- 27185138 TI - The fast and effective isolation of nanocellulose from selected cellulosic feedstocks. AB - A new process for the production of nanocellulose from selected cellulose containing natural materials has been developed. The liquefaction reaction, using glycols and mild acid catalysis (methane sulphonic acid), was applied to four model materials, namely cotton linters, spruce wood, eucalyptus wood and Chinese silver grass. The process contains only four steps, the milling, the glycolysis reaction, centrifugation and final rinsing with an organic solvent. The nanocrystalline cellulose recovery was between 56% and 75%. The crystallinity index was greater than that of the starting materials due to the liquefaction of lignin, hemicelluloses and amorphous cellulose. The final product was a stable, highly concentrated nanocrystalline cellulose suspension in the organic medium. The liquid residue, after the liquefaction of the cotton linters contained significant quantities of levulinic acid. Different sugars were identified in the liquid residues that were derived from cellulose and hemicelluloses during the liquefaction reaction. PMID- 27185139 TI - Development of nanocellulose scaffolds with tunable structures to support 3D cell culture. AB - Swollen three-dimensional nanocellulose films and their resultant aerogels were prepared as scaffolds towards tissue engineering application. The nanocellulose hydrogels with various swelling degree (up to 500 times) and the resultant aerogels with desired porosity (porosity up to 99.7% and specific surface area up to 308m(2)/g) were prepared by tuning the nanocellulose charge density, the swelling media conditions, and the material processing approach. Representative cell-based assays were applied to assess the material biocompatibility and efficacy of the human extracellular matrix (ECM)-mimicking nanocellulose scaffolds. The effects of charge density and porosity of the scaffolds on the biological tests were investigated for the first time. The results reveal that the nanocellulose scaffolds could promote the survival and proliferation of tumor cells, and enhance the transfection of exogenous DNA into the cells. These results suggest the usefulness of the nanocellulose-based matrices in supporting crucial cellular processes during cell growth and proliferation. PMID- 27185141 TI - Application of model bread baking in the examination of arabinoxylan-protein complexes in rye bread. AB - The changes in molecular mass of arabinoxylan (AX) and protein caused by bread baking process were examined using a model rye bread. Instead of the normal flour, the dough contained starch, water-extractable AX and protein which were isolated from rye wholemeal. From the crumb of selected model breads, starch was removed releasing AX-protein complexes, which were further examined by size exclusion chromatography. On the basis of the research, it was concluded that optimum model mix can be composed of 3-6% AX and 3-6% rye protein isolate at 94 88% of rye starch meaning with the most similar properties to low extraction rye flour. Application of model rye bread allowed to examine the interactions between AX and proteins. Bread baked with a share of AX, rye protein and starch, from which the complexes of the highest molar mass were isolated, was characterized by the strongest structure of the bread crumb. PMID- 27185140 TI - An environment-friendly and multi-functional absorbent from chitosan for organic pollutants and heavy metal ion. AB - Developing environment-friendly green absorbents for disposal of wastewater remains to be studied. In this paper, the cross-linked chitosan aerogel (CsA) as an environment-friendly absorbent was obtained by a simple method involving cross linked process and freeze drying technique. Compared with conventional absorbents, the porous chitosan aerogel was provided with unique properties such as low density (0.0283g/cm(3)), high porosity (97.98%) and outstanding adsorption performance. The chitosan aerogel also displayed good reusability and excellent elasticity with a maximal thickness recovery up to 96.8% of the original thickness. The as-prepared absorbent exhibited preferable adsorption capacities for crude oil, diesel and copper ion (41.07g/g, 31.07g/g and 21.38mg/g, respectively). The aerogel can collect a wide range of organic solvents and oils with absorption capacities up to 40 times their own weight, depending on the density and viscosity of the liquids. The adsorption capacity for heavy metal ion was also considerable and the maximum adsorption capacity (qm) of the aerogel for copper ion was 35.08mg/g according to Langmuir isotherm model. Consequently, the chitosan aerogel with versatile adsorption properties has a good potential for wastewater treatment in environmental application. PMID- 27185142 TI - Oxidation of amylose and amylopectin by hydroxyl radicals assessed by electrospray ionisation mass spectrometry. AB - The hydroxyl radicals (HO) are one of the most reactive oxygen species (ROS) involved in the oxidative damage of biological molecules, including carbohydrates. During the industrial processing of food, ROS can be formed. In order to identify the structural changes induced in starch by oxidation, amylose, amylopectin, and maltotriose, an oligosaccharide structurally related to these polysaccharides, were subjected to oxidation with HO generated under Fenton reaction conditions (Fe(2+)/H2O2). The oxidised polysaccharides were hydrolysed by alpha-amylase and the obtained oligosaccharides were fractionated by ligand exchange/size-exclusion chromatography. Both acidic and neutral alpha-amylase resistant oligosaccharides were characterized by mass spectrometry. In oxidised neutral products, new keto, hydroxyl, and hydroperoxy moieties, and oxidative ring scission were observed at the reducing end of the oligosaccharides. The acid sugar residues occurred at the reducing end and included gluconic and glucuronic acid derivatives, and acids formed by oxidative ring scission, namely, arabinonic, erythronic, glyceric and glycolic acids. PMID- 27185143 TI - Synthesis of polyvinyl alcohol/cellulose nanofibril hybrid aerogel microspheres and their use as oil/solvent superabsorbents. AB - Superhydrophobic and crosslinked poly(vinyl alcohol) (PVA)/cellulose nanofibril (CNF) aerogel microspheres were prepared via a combination of the water-in-oil (W/O) emulsification process with the freeze-drying process, followed by thermal chemical vapor deposition of methyltrichlorosilane. The oil phase and the cooling agent were judiciously selected to ensure that the frozen ice microspheres can be easily separated from the emulsion system. The silanized microspheres were highly porous with a bulk density ranging from 4.66 to 16.54mg/cm(3). The effects of the solution pH, stirring rate, and emulsifier concentration on the morphology and microstructure of the aerogel microspheres were studied. The highly porous structure of the ultralight aerogel microspheres demonstrated an ultrahigh crude oil absorption capacity (up to 116 times its own weight). This study provides a novel approach for the large-scale preparation of polymeric aerogel microspheres with well-controlled particle sizes that can be used for various applications including oil and chemical spill/leak clean-up. PMID- 27185144 TI - Evaluation of different methods to prepare superabsorbent hydrogels based on deacetylated gellan. AB - This study stands out for analyzing distinct ways of preparing hydrogels from deacetylated gellan gum that have high swelling capacity and good thermal resistance. We carried out a thorough investigation, applying various combinations of different experimental parameters. Two preparation methods were evaluated, in which the pH was adjusted before or after thermal treatment of the gellan solution, with subsequent addition of the crosslinking agent, to assess the influence of preparation method on the conformation of the gellan chains regarding formation of double helices. The pH range tested varied from acid (2, 3 or 4) to basic (8, 9 or 10). Gellan solution was prepared in different concentrations. Both pure gellan and hydrogel samples were characterized by Fourier-transform infrared spectroscopy and thermogravimetry. Pure gellan was also characterized by atomic absorption spectroscopy. The swelling degree of the hydrogels was analyzed. The results showed that all the hydrogels had high swelling capacity (>400%), so they can be considered superabsorbent materials. Hydrogels prepared with acid pH in general had lower thermal resistance than samples prepared in alkaline pH, regardless of the preparation method. Samples prepared with alkaline pH tended to have initial decomposition temperature similar to that of pure gellan. PMID- 27185145 TI - Immune-enhancing activity of extracellular polysaccharides isolated from Rhizopus nigricans. AB - Extracellular polysaccharides (EPS1-1) was extracted from fermentation liquor of Rhizopus nigricans and evaluated its immune-enhancing activities in vitro and in vivo. Results suggested that the proliferation of lymphocyte was stimulated after treated with EPS1-1. Moreover, the activities of macrophages were enhanced by increasing the activities of phagocytosis and acid phosphatase, the production of NO and the mRNA levels of IL-2, TNF-alpha and iNOS. Furthermore, EPS1-1 could significantly boost the immunity of normal and immunosuppressed mice, which included the increase of loaded swimming time, footpad swelling, organ index and the secretion of IL-2 and TNF-alpha in serum, thus suggesting that EPS1-1 could improve the body immunity through cellular immunity and humoral immunity. These findings provided further insights into the potential use of EPS1-1 as immunopotentiator or new function food. PMID- 27185146 TI - Controlled production of polysaccharides-exploiting nutrient supply for levan and heteropolysaccharide formation in Paenibacillus sp. AB - Bacterial exopolysaccharides (EPSs) are promising sustainable alternatives to synthetic polymers. Here we describe the production and characterization of different EPSs produced by the recently isolated Paenibacillus sp. 2H2. A final EPS titer of 4.54gL(-1) was recovered after a 17-h fermentation, corresponding to a volumetric productivity of 0.27gL(-1)h(-1). Remarkably, supplying the fermentation with specific carbon and nitrogen sources could be exploited for the production of different polymers. A pure heteropolysaccharide composed of glucose, mannose, galactose, and glucuronic acid (3.5:2:1:0.1) was obtained when using glucose/glycerol and peptone as substrates. A pure levan-type polymer or mixture of both polymers was observed with sucrose and NaNO3 or peptone. To our knowledge, this is the first report that nutrients, particularly nitrogen sources, can be used to fine-tune EPS production in Paenibacillaceae. Rheological characterization of the heteropolysaccharide revealed impressive thickening properties, suggesting its potential application in commodity materials. PMID- 27185147 TI - Fabrication of bacterial cellulose-ZnO composite via solution plasma process for antibacterial applications. AB - Zinc oxide (ZnO) was successfully synthesized by applying a solution plasma, a plasma discharge in a liquid phase, without the addition of a reducing agent and simultaneously deposited into a bacterial cellulose pellicle that functioned as a template. By the reasons of its nano-sized structure as well as favorable porous configuration, the BC pellicle has been proved to be a splendid upholding template for the coordination of ZnO. In addition, the ZnO-deposited BC composites demonstrated strong antibacterial activity without a photocatalytic reaction against both Staphylococcus aureus and Escherichia coli. Hence, the ZnO deposited BC composites can be used as an antibacterial material in wound dressing and water disinfection applications. PMID- 27185148 TI - Optimization of infrared-assisted extraction of Bletilla striata polysaccharides based on response surface methodology and their antioxidant activities. AB - Bletilla striata polysaccharides (BSP) have attracted extensive research interest due to their potential medical application. Herein, infrared-assisted technique is employed for the first time to extract BSP from B. striata (Thunb.) Reichb.f. based on a Box-Behnken design (BBD) and response surface methodology, with the optimum extraction parameters as follows: 75 degrees C extraction temperature, 2.5h extraction time; and water to solid ratio (53ml/g). Based on it, 43.95+/ 0.26% yield of crude BSP was obtained. Subsequently, crude BSP was further decolorized, deproteinized, freeze-dried, and purified by a DEAE-52 cellulose column. Furthermore, the micro-structure and a triple-helical structure of BSP were characterized. Fourier transform infrared spectra confirmed its polysaccharide characterization via typical peaks. In addition, the significant in vitro antioxidant profiles of BSP were demonstrated by superoxide anion radical-scavenging assay, hydroxyl radical scavenging assay, DPPH free radical scavenging activity and chelation of ferrous ions. Taken together, this study provide an efficient extraction technique for BSP as a promising natural antioxidant. PMID- 27185149 TI - Polyelectrolyte complex nanoparticles from cationised gelatin and sodium alginate for curcumin delivery. AB - Self assembled hybrid polyelectrolyte complex (PEC) nanoparticles are prepared from cationically modified gelatin and sodium alginate (Alg) by electrostatic complexation between the polymers. Cationised gelatin (CG) is prepared by the reaction of gelatin with ethylenediamine. Structural changes in gelatin, after modification with ethylenediamine are investigated by XRD and (1)H NMR spectroscopy. Hybrid polyelectrolyte nanoparticles, labeled CG/Alg, are prepared by simple mixing of CG and Alg. CG/Alg complex shows spherical morphology as confirmed by scanning electron microscopy. These polyelectrolyte complex nanoparticles can be used for the encapsulation and delivery of natural antioxidant curcumin to carcinoma cells. CG/Alg nanoparticles show curcumin encapsulation efficiency of 69% and exhibit sustained release of curcumin in vitro. Anticancer activity of curcumin loaded CG/Alg nanoparticles towards MCF-7 cells is disclosed by MTT assay. Intracellular uptake of the drug encapsulated nanoparticles is confirmed by fluorescent imaging. PMID- 27185150 TI - Hydrolyzability of xylan after adsorption on cellulose: Exploration of xylan limitation on enzymatic hydrolysis of cellulose. AB - During pretreatment of lignocellulosic materials, the dissolved xylan would re adsorb on cellulose, and then inhibits the cellulose hydrolysis by cellulases. However, the hydrolyzability of xylan adsorbed on cellulose is not clear. In this work, the adsorption behavior of xylans on celluloses and the hydrolysis of adsorbed xylan by xylanase (XYL) were investigated. The results indicated that the adsorption of beechwood xylan (BWX) and oat spelt xylan (OSX) on Avicel was conformed to Langmuir-type adsorption isotherm. Higher ion strength increased the adsorption of BWX on Avicel, but not that of OSX. Both BWX and OSX adsorbed on Avicel and corn stover after dilute acid pretreatment (CS-DA) could be hydrolyzed by XYL. Compared to OSX, BWX adsorbed on cellulosic materials could be more easily hydrolyzed by XYL. Thus, supplementation of XYL could hydrolyze the xylan adsorbed on cellulose and potentially improved hydrolysis efficiency of lignocelluloses. PMID- 27185152 TI - Visualisation of xanthan conformation by atomic force microscopy. AB - Direct visual evidence obtained by atomic force microscopy demonstrates that when xanthan is adsorbed from aqueous solution onto the heterogeneously charged substrate mica, its helical conformation is distorted. Following adsorption it requires annealing for several hours to restore its ordered helical state. Once the helix state reforms, the AFM images obtained showed clear resolution of the periodicity with a value of 4.7nm consistent with the previously predicted models. In addition, the images also reveal evidence that the helix is formed by a double strand, a clarification of an ambiguity of the xanthan ultrastructure that has been outstanding for many years. PMID- 27185151 TI - Structural characterization of complexes prepared with glycerol monoestearate and maize starches with different amylose contents. AB - Morphology and different structural features of V-amylose complexes prepared with different concentrations (1%, 2%, 3%) of glycerol monostearate (GMS) and normal maize (NMS), waxy maize (WMS), and high amylose maize (HAMS) starches were evaluated using X-ray diffraction, differential scanning calorimetry, scanning electronic microscopy (SEM), atomic force microscopy (AFM), and transmission electronic microscopy (TEM). There was inclusion complex formation between all starches and GMS regardless of emulsifier concentration, with exception of WMS 2%GMS and WMS-3%GMS samples. All of the inclusion complexes displayed a V-type crystalline pattern and endothermic dissociation peaks between 115 and 120 degrees C. They also displayed faceted crystalline structures with a tendency of the crystals to aggregate and form agglomerates of various sizes. TEM images of the complexes showed an aggregated strand structure interwoven with the GMS. Emulsifier and amylose quantities directly influenced complex formation. At high GMS concentrations, there was higher tendency of emulsifier to self-associate rather than form complexes with amylose. PMID- 27185153 TI - Catalytic pyrolysis of cellulose in ionic liquid [bmim]OTf. AB - This study discussed the catalytic cracking process of cellulose in ionic liquid 1-butyl-3-methylimidazolium trifluoromethanesulfonate ([bmim]OTF) under 180 degrees C, 240 degrees C and 340 degrees C, found that [bmim]OTF is an effective catalyst which can effectively reduce the pyrolysis temperature(nearly 200 degrees C) of the cellulose. FRIR, XRD and SEM were used to analyze the structure characterization of fiber before and after the cracking; GC-MS was used for liquid phase products analysis; GC was used to analyze gas phase products. The results showed that the cellulose pyrolysis in [bmim]OTf mainly generated CO2, CO and H2, also generated 2-furfuryl alcohol, 2,5-dimethyl-1,5-diallyl-3-alcohol, 1,4-butyrolactone, 5-methyl furfural, 4-hydroxy butyric acid, vinyl propionate, 1 acetoxyl group-2-butanone, furan formate tetrahydrofuran methyl ester liquid product, and thus simulated the evolution mechanism of cellulose pyrolysis products based on the basic model of cellulose monomer. PMID- 27185154 TI - Synthesis and characterization of ZnO:CeO2:nanocellulose:PANI bionanocomposite. A bimodal agent for arsenic adsorption and antibacterial action. AB - In the present study we report the generation of a bimodal, ZnO:CeO2:nanocellulose:polyaniline bionanocomposite having an appreciable remediation efficiency for dissolved Arsenic along with a noticeable antibacterial activity. The microstructural analysis of the synthesized bionanocomposite was carried out by TEM, XRD and FTIR studies, which confirmed the incorporation of the nanoscaled ZnO and CeO2 in the polymeric nanocellulose:polyaniline matrix. The bionanocomposite exhibited a remediation efficiency above ~95% against As under different adsorbent concentrations and pH conditions. The biosorption mechanism of As on the nanobiosorbent was found to conform to the Freundlich and Dubinin-Radushkevich isotherms. Antibacterial assays for the bionanocomposite showed a high antibacterial activity with MIC50 values of 10.6MUgml(-1) against the Gram-positive Bacillus subtilis and 10.3MUgml(-1) against the Gram-negative Escherichia coli. Thus, the bionanocomposite shall be of high interest as a novel and sustainable matrix for the design of coats/devices that effectuate arsenic adsorption and microbial control, to generate contaminant free potable water. PMID- 27185155 TI - Removal of Cd(II) and Pb(II) from wastewater by using triethylenetetramine functionalized grafted cellulose acetate-manganese dioxide composite. AB - In this manuscript, we have studied the removal of Cd(II) and Pb(II) ions from aqueous solution by using triethylenetetramine functionalized cellulose acetate grafted with the copolymer-manganese dioxide composite. The novel sorbent cellulose was extracted from the mangrove trees (Avicennia marina) and it was then acetylated and grafted with acrylamide. The sorbent composite was designed to interact simultaneously with higher metal loading by complexation-adsorption process. FT-IR, SEM, EDAX and TGA techniques were employed to characterize the cellulose modified composite. Sorption equilibria were established after 30min and their data were described by Langmuir and Freundlich models. The functionalized hybrid cellulose composite showed maximum adsorption capacity 82.06 and 196.84mgg(-1) for Cd(II) and Pb(II), respectively. The studied metal ions were successfully recovered from real wastewater samples of different matrices. PMID- 27185156 TI - Increased Melatonin Signaling Is a Risk Factor for Type 2 Diabetes. AB - Type 2 diabetes (T2D) is a global pandemic. Genome-wide association studies (GWASs) have identified >100 genetic variants associated with the disease, including a common variant in the melatonin receptor 1 b gene (MTNR1B). Here, we demonstrate increased MTNR1B expression in human islets from risk G-allele carriers, which likely leads to a reduction in insulin release, increasing T2D risk. Accordingly, in insulin-secreting cells, melatonin reduced cAMP levels, and MTNR1B overexpression exaggerated the inhibition of insulin release exerted by melatonin. Conversely, mice with a disruption of the receptor secreted more insulin. Melatonin treatment in a human recall-by-genotype study reduced insulin secretion and raised glucose levels more extensively in risk G-allele carriers. Thus, our data support a model where enhanced melatonin signaling in islets reduces insulin secretion, leading to hyperglycemia and greater future risk of T2D. The findings also imply that melatonin physiologically serves to inhibit nocturnal insulin release. PMID- 27185158 TI - Saving the Military Surgeon: Maintaining Critical Clinical Skills in a Changing Military and Medical Environment. PMID- 27185157 TI - Integrated metabolomic and transcriptome analyses reveal finishing forage affects metabolic pathways related to beef quality and animal welfare. AB - Beef represents a major dietary component and source of protein in many countries. With an increasing demand for beef, the industry is currently undergoing changes towards naturally produced beef. However, the true differences between the feeding systems, especially the biochemical and nutritional aspects, are still unclear. Using transcriptome and metabolome profiles, we identified biological pathways related to the differences between grass- and grain-fed Angus steers. In the latissimus dorsi muscle, we have recognized 241 differentially expressed genes (FDR < 0.1). The metabolome examinations of muscle and blood revealed 163 and 179 altered compounds in each tissue (P < 0.05), respectively. Accordingly, alterations in glucose metabolism, divergences in free fatty acids and carnitine conjugated lipid levels, and altered beta-oxidation have been observed. The anti-inflammatory n3 polyunsaturated fatty acids are enriched in grass finished beef, while higher levels of n6 PUFAs in grain finished animals may promote inflammation and oxidative stress. Furthermore, grass-fed animals produce tender beef with lower total fat and a higher omega3/omega6 ratio than grain-fed ones, which could potentially benefit consumer health. Most importantly, blood cortisol levels strongly indicate that grass-fed animals may experience less stress than the grain-fed individuals. These results will provide deeper insights into the merits and mechanisms of muscle development. PMID- 27185159 TI - Metformin Alleviates Altered Erythrocyte Redox Status During Aging in Rats. AB - Metformin, a biguanide drug commonly used to treat type 2 diabetes, has been noted to function as a caloric restriction mimetic. Its antidiabetic effect notwithstanding, metformin is currently being considered an antiaging drug candidate, although the molecular mechanisms have not yet been unequivocally established. This study aims to examine whether short-term metformin treatment can provide protective effects against oxidative stress in young and old-age rats. Young (age 4 months) and old (age 24 months) male Wistar rats were treated with metformin (300 mg/kg b.w.) for 4 weeks. At the end of the treatment period, an array of biomarkers of oxidative stress were evaluated, including plasma antioxidant capacity measured in terms of ferric reducing ability of plasma (FRAP), reactive oxygen species (ROS), lipid peroxidation (MDA), reduced glutathione (GSH), total plasma thiol (SH), plasma membrane redox system (PMRS), protein carbonyl (PCO), advanced oxidation protein products (AOPPs), and advanced glycation end products (AGEs) in control and experimental groups. Metformin treatment resulted in an increase in FRAP, GSH, SH, and PMRS activities in both age groups compared to respective controls. On the other hand, treated groups exhibited significant reductions in ROS, MDA, PCO, AOPP, and AGE level. Save for FRAP and protein carbonyl, the effect of metformin on all other parameters was more pronounced in old-aged rats. Metformin caused a significant increase in the PMRS activity in young rats, however, the effect was less pronounced in old rats. These findings provide evidence with respect to restoration of antioxidant status in aged rats after short-term metformin treatment. The findings substantiate the putative antiaging role of metformin. PMID- 27185160 TI - "Those edibles hit hard": Exploration of Twitter data on cannabis edibles in the U.S. AB - AIMS: Several states in the U.S. have legalized cannabis for recreational or medical uses. In this context, cannabis edibles have drawn considerable attention after adverse effects were reported. This paper investigates Twitter users' perceptions concerning edibles and evaluates the association edibles-related tweeting activity and local cannabis legislation. METHODS: Tweets were collected between May 1 and July 31, 2015, using Twitter API and filtered through the eDrugTrends/Twitris platform. A random sample of geolocated tweets was manually coded to evaluate Twitter users' perceptions regarding edibles. Raw state proportions of Twitter users mentioning edibles were ajusted relative to the total number of Twitter users per state. Differences in adjusted proportions of Twitter users mentioning edibles between states with different cannabis legislation status were assesed via a permutation test. RESULTS: We collected 100,182 tweets mentioning cannabis edibles with 26.9% (n=26,975) containing state level geolocation. Adjusted percentages of geolocated Twitter users posting about edibles were significantly greater in states that allow recreational and/or medical use of cannabis. The differences were statistically significant. Overall, cannabis edibles were generally positively perceived among Twitter users despite some negative tweets expressing the unreliability of edible consumption linked to variability in effect intensity and duration. CONCLUSION: Our findings suggest that Twitter data analysis is an important tool for epidemiological monitoring of emerging drug use practices and trends. Results tend to indicate greater tweeting activity about cannabis edibles in states where medical THC and/or recreational use are legal. Although the majority of tweets conveyed positive attitudes about cannabis edibles, analysis of experiences expressed in negative tweets confirms the potential adverse effects of edibles and calls for educating edibles-naive users, improving edibles labeling, and testing their THC content. PMID- 27185162 TI - Unique epitopes for carbonic anhydrase II autoantibodies related to autoimmune retinopathy and cancer-associated retinopathy. AB - High titers of anti-carbonic anhydrase II (anti-CA II) autoantibodies were detected in sera of patients with autoimmune retinopathies (AR), including cancer associated retinopathy (CAR) and also in normal population. The goal was to investigate whether unique immunodominant epitopes for anti-CAII autoantibodies occur in AR and CAR. A cohort of 216 patients with symptoms of AR and CAR and healthy controls, seropositive for anti-CA II autoantibodies were analyzed for the prevalence of CAII major domains. Autoantibody titers against CAII in sera were determined by ELISA. Biotinylated 12-mer synthetic peptides, overlapping the entire sequence of CAII, were coated onto a microplate and monospecific sera were tested for their ability to bind specific peptides by ELISA. We identified 3 epitopes common for AR, CAR and control subjects but the key epitopes were significantly different between sera from different groups (p = 0.009). Ninety one percent of AR sera predominantly reacted with the N-terminal epitope 85-90 (p < 0.0001), which corresponded to the catalytic core of the enzyme. The major epitope for 77% of CAR autoantibodies was found to be reactive with the peptide 218-222 (P = 0.0005) clustered within the alpha-helix. The analysis of epitope position in a 3D structure of the native CAII revealed their partial or full exposure on the protein surface. Anti-CAII autoantibodies from normal healthy controls did not share the major determinants with either group of patients. We also observed an epitope shift in antibody recognition from the AR-like epitope profile to the CAR-like profile in a patient who developed cancer 2 years after initial symptoms of vision loss (p < 0.0001). In conclusion, autoantibodies against CAII recognized different epitopes, depending whether they originated in patients with or without cancer. Also, antibodies targeted different determinates within the molecule during the development of retinopathy from non-paraneoplastic to paraneoplastic, suggesting an intramolecular epitope spreading phenomenon. Accurate distinction between AR and CAR is critical in designing immunotherapies and better diagnosis for those two conditions. PMID- 27185163 TI - Resident corneal c-fms(+) macrophages and dendritic cells mediate early cellular infiltration in adenovirus keratitis. AB - The cornea contains a heterogeneous population of antigen-presenting cells with the capacity to contribute to immune responses. Adenovirus keratitis is a severe corneal infection with acute and chronic phases. The role of resident corneal antigen-presenting cells in adenovirus keratitis has not been studied. We utilized transgenic MaFIA mice in which c-fms expressing macrophages and dendritic cells can be induced to undergo apoptosis, in a mouse model of adenovirus keratitis. Clinical keratitis and recruitment of myeloperoxidase and CD45(+) cells were diminished in c-fms depleted, adenovirus infected mice, as compared to controls, consistent with a role for myeloid-lineage cells in adenovirus keratitis. PMID- 27185165 TI - Surgical resection of medulla oblongata hemangioblastomas: outcome and complications. AB - OBJECT: The purpose of this study was to analyze the surgical outcome and complications of a single-center series of medulla oblongata (MO) hemangioblastomas. METHODS: We retrospectively reviewed the medical charts of all medulla oblongata hemangioblastomas operated on at our institution between 1996 and 2015. All patients had a pre- and postoperative MRI and a minimum follow-up of 6 months. Patients were scored according to the Karnofsky Performance Scale (KPS) and McCormick Scale at the moment of admission, discharge and the last follow-up. RESULTS: Thirty-one surgical procedures were performed on 27 patients (16 females and 11 males). The mean age was 33 years, and 93 % of patients had von Hippel Lindau (VHL) disease. Three patients experienced very complicated postoperative courses, with one case ending in the death of the patient. Two patients required tracheostomy. According to McCormick's classification, 7 (23 %) of the 31 operations resulted in aggravation and 23 (74 %) in no change. Considering the seven patients with aggravation at discharge, four patients (60 %) returned to their preoperative status, one (14 %) improved but remained below his preoperative McCormick grade and two (29 %) did not improve. At last follow up, KPS was ameliorated in 53 %, stable in 40 % and worsened in 7 % of cases. CONCLUSION: Surgery of medulla oblongata hemangioblastomas is a challenging procedure characterized by an acceptable morbidity. Transient morbidity is not negligible even if the long-term outcome is in most cases favorable. A compromised neurological condition seems to be the best predictor of unfavorable outcome. PMID- 27185164 TI - A 12-week open-label, randomized, controlled trial and 24-week extension to assess the efficacy and safety of fluticasone propionate/formoterol in children with asthma. AB - OBJECTIVES: The present study was conducted to assess the efficacy, safety and tolerability of fluticasone propionate/formoterol fumarate combination therapy (FP/FORM; Flutiform(r)) compared with fluticasone propionate/salmeterol xinafoate (FP/SAL; Seretide(r) Evohaler(r)) in children with asthma. METHODS: This was an open-label, randomized, controlled, phase III trial and extension. Patients aged 4-12 years with reversible asthma [% predicted forced expiratory volume in 1 second (FEV1) 60-100%; documented reversibility of ?15% in FEV1] were randomized to receive FP/FORM (100/10 ug b.i.d.) or FP/SAL (100/50 ug b.i.d.) for 12 weeks. Eligible patients completing the 12-week core phase entered a 24-week extension phase with FP/FORM (100/10 ug b.i.d.). The primary efficacy endpoint was the change in predose FEV1 from day 0 to day 84. Secondary efficacy endpoints included change in predose to 2-hours postdose FEV1 from day 0 to day 84, peak expiratory flow rate (PEFR), patient-reported outcomes, rescue-medication use and asthma exacerbations. RESULTS: In total, 211 patients were randomized and 210 completed the core phase; of these patients, 208 entered and 205 completed the extension phase of the study. Predose FEV1 increased from day 0 to day 84 [FP/FORM, 182 ml; 95% confidence interval (CI), 127, 236; FP/SAL, 212 ml, 95% CI, 160, 265] and FP/FORM was noninferior to FP/SAL: least squares (LS) mean treatment difference: -0.031 (95% CI, -0.093, 0.031; p = 0.026). Secondary efficacy analyses indicated similar efficacy with both therapies. There were no notable differences observed in the safety and tolerability profile between treatments. No safety concerns were identified with long-term FP/FORM therapy, and there was no evidence of an effect of FP/FORM on plasma cortisol. CONCLUSIONS: FP/FORM improved lung function and measures of asthma control with comparable efficacy to FP/SAL, and demonstrated a favourable safety and tolerability profile in children aged 4-12 years. PMID- 27185166 TI - Early-onset parkinsonism due to compound heterozygous POLG mutations. PMID- 27185167 TI - Low frequency of GCH1 and TH mutations in Parkinson's disease. AB - BACKGROUND: The causes of Parkinson's disease (PD) are unknown in the majority of patients. The GCH1 gene encodes GTP-cyclohydrolase I, an important enzyme in dopamine synthesis. Co-occurrence of dopa-responsive dystonia (DRD) and a PD phenotype has been reported in families with GCH1 mutations. Recently, rare coding variants in GCH1 were found to be enriched in PD patients, indicating a role for the enzyme in the neurodegenerative process. METHODS: To further elucidate the contribution of GCH1 mutations to sporadic PD, we examined its coding exons in a targeted deep sequencing study of 509 PD patients (mean age at onset 56.7 +/- 12.0 years) and 230 controls. We further included the tyrosine hydroxylase gene TH, also known to cause DRD. Gene dose assessments were performed to screen for large copy number variants in a subset of 48 patients with early-onset PD. RESULTS: No putatively pathogenic GCH1 mutations were found. The frequency of rare heterozygous variants in the TH gene was 0.69% (7/1018) in the patient group and 0.22% (1/460) in the control group (p = 0.45). CONCLUSIONS: Previous studies have found that coding variants in the GCH1 gene may be considered a risk factor for PD. Our study indicates that mutations in GCH1 are rare in late-onset PD. Several patients carried heterozygous variants in the TH gene that may affect protein function. Our study was not designed to determine with certainty if any of these variants play a role as risk factors for late onset PD. PMID- 27185161 TI - The role of integrins in glaucoma. AB - Integrins are a family of heterodimeric transmembrane receptors that mediate adhesion to the extracellular matrix (ECM). In addition to their role as adhesion receptors, integrins can act as ''bidirectional signal transducers'' that coordinate a large number of cellular activities in response to the extracellular environment and intracellular signaling events. This bidirectional signaling helps maintain tissue homeostasis. Dysregulated bidirectional signaling, however, could trigger the propagation of feedback loops that can lead to the establishment of a disease state such as glaucoma. Here we discuss the role of integrins and bidirectional signaling as they relate to the glaucomatous phenotype with special emphasis on the alphavbeta3 integrin. We present evidence that this particular integrin may have a significant impact on the pathogenesis of glaucoma. PMID- 27185168 TI - Race and Sex Differences in the Incidence and Prognostic Significance of Silent Myocardial Infarction in the Atherosclerosis Risk in Communities (ARIC) Study. AB - BACKGROUND: Race and sex differences in silent myocardial infarction (SMI) are not well established. METHODS AND RESULTS: The analysis included 9498 participants from the Atherosclerosis Risk in Communities (ARIC) study who were free of cardiovascular disease at baseline (visit 1, 1987-1989). Incident SMI was defined as ECG evidence of MI without clinically documented MI (CMI) after the baseline until ARIC visit 4 (1996-1998). Coronary heart disease and all-cause deaths were ascertained starting from ARIC visit 4 until 2010. During a median follow-up of 8.9 years, 317 participants (3.3%) developed SMI and 386 (4.1%) developed CMI. The incidence rates of both SMI and CMI were higher in men (5.08 and 7.96 per 1000-person years, respectively) than in women (2.93 and 2.25 per 1000-person years, respectively; P<0.0001 for both). Blacks had a nonsignificantly higher rate of SMI than whites (4.45 versus 3.69 per 1000-person years; P=0.217), but whites had higher rate of CMI than blacks (5.04 versus 3.24 per 1000-person years; P=0.002). SMI and CMI (compared with no MI) were associated with increased risk of coronary heart disease death (hazard ratio, 3.06 [95% confidence interval, 1.88-4.99] and 4.74 [95% confidence interval, 3.26 6.90], respectively) and all-cause mortality (hazard ratio, 1.34 [95% confidence interval, 1.09-1.65] and 1.55 [95% confidence interval, 1.30-1.85], respectively). However, SMI and CMI were associated with increased mortality among both men and women, with potentially greater increased risk among women (interaction P=0.089 and 0.051, respectively). No significant interactions by race were detected. CONCLUSIONS: SMI represents >45% of incident MIs and is associated with poor prognosis. Race and sex differences in the incidence and prognostic significance of SMI exist that may warrant considering SMI in personalized assessments of coronary heart disease risk. PMID- 27185171 TI - IL-23 Promotes Myocardial I/R Injury by Increasing the Inflammatory Responses and Oxidative Stress Reactions. AB - BACKGROUND/AIMS: Inflammation and oxidative stress play an important role in myocardial ischemia and reperfusion (I/R) injury. We hypothesized that IL-23, a pro-inflammatory cytokine, could promote myocardial I/R injury by increasing the inflammatory response and oxidative stress. METHODS: Male Sprague-Dawley rats were randomly assigned into sham operated control (SO) group, ischemia and reperfusion (I/R) group, (IL-23 + I/R) group and (anti-IL-23 + I/R) group. At 4 h after reperfusion, the serum concentration of lactate dehydrogenase (LDH), creatine kinase (CK) and the tissue MDA concentration and SOD activity were measured. The infarcte size was measured by TTC staining. Apoptosis in heart sections were measured by TUNEL staining. The expression of HMGB1 and IL-17A were detected by Western Blotting and the expression of TNF-alpha and IL-6 were detected by Elisa. RESULTS: After 4 h reperfusion, compared with the I/R group, IL-23 significantly increased the infarct size, the apoptosis of cardiomyocytes and the levels of LDH and CK (all P < 0.05). Meanwhile, IL-23 significantly increased the expression of eIL-17A, TNF-alpha and IL-6 and enhanced both the increase of the MDA level and the decrease of the SOD level induced by I/R (all P<0.05). IL-23 had no effect on the expression of HMGB1 (p > 0.05). All these effects were abolished by anti-IL-23 administration. CONCLUSION: The present study suggested that IL-23 may promote myocardial I/R injury by increasing the inflammatory responses and oxidative stress reaction. PMID- 27185170 TI - Process-based approach to modeling recurrent-event data explicated on the basis of occurrences of tooth losses in two different prosthetic treatment concepts. AB - BACKGROUND: In studies comparing different prosthetic treatment concepts the repeated loss of teeth was chosen as the primary outcome. The resulting data appear to represent a data structure of recurrent events. However, the application of an existing method for recurrent events is far from straightforward. Often only the first event or the final state is analyzed using Kaplan-Meier survival statistics, thereby giving a great deal of information away. METHODS: The paper presents a strategy for the analysis of recurrent data using a previously published study on the influence of different prosthetic treatment concepts for the shortened dental arch on tooth loss. A method based on cumulative sample history functions of recurrent events was adjusted for tooth loss. The shapes of these cumulative functions suggest a time dependency of the recurrence rate. To keep the model as simple as possible, a tripartite Poisson process (which assumes piecewise time-independent rates) was fitted to the cumulative mean functions stratified by treatment. RESULTS: Within the middle interval of the three-phasic process, the treatment effects differ significantly, which is interpreted as a delay of tooth loss due to the use of one type of prosthesis (fixed) compared with the other (removable). CONCLUSIONS: An analysis based on cumulative history functions is based on process, therefore, temporally changing characteristics are better captured than in methods for survival analyses. The presented approach offers useful new insight into the temporal behavior of ongoing tooth loss after prosthetic treatment. TRIAL REGISTRATION: The trial has been registered at controlled-trials.com under ISRCTN97265367 (registration date 4 April 2008). PMID- 27185169 TI - Role of prophylactic central compartment lymph node dissection in clinically N0 differentiated thyroid cancer patients: analysis of risk factors and review of modern trends. AB - In the last years, especially thanks to a large diffusion of ultrasound-guided FNBs, a surprising increased incidence of differentiated thyroid cancer (DTC), "small" tumors and microcarcinomas have been reported in the international series. This led endocrinologists and surgeons to search for "tailored" and "less aggressive" therapeutic protocols avoiding risky morbidity and useless "overtreatment". Considering the most recent guidelines of referral endocrine societies, we analyzed the role of routine or so-called prophylactic central compartment lymph node dissection (RCLD), also considering its benefits and risks. Literature data showed that the debate is still open and the surgeons are divided between proponents and opponents of its use. Even if lymph node metastases are commonly observed, and in up to 90% of DTC cases micrometastases are reported, the impact of lymphatic involvement on long-term survival is subject to intensive research and the best indications of lymph node dissection are still controversial. Identification of prognostic factors for central compartment metastases could assist surgeons in determining whether to perform RLCD. Considering available evidence, a general agreement to definitely reserve RCLD to "high-risk" cases was observed. More clinical researches, in order to identify risk factors of meaningful predictive power and prospective long-term randomized trials, should be useful to validate this selective approach. PMID- 27185172 TI - Both the apoptotic suicide pathway and phagocytosis are required for a programmed cell death in Caenorhabditis elegans. AB - BACKGROUND: Programmed cell deaths in the nematode Caenorhabditis elegans are generally considered suicides. Dying cells are engulfed by neighboring cells in a process of phagocytosis. To better understand the interaction between the engulfment and death processes, we analyzed B.al/rapaav cell death, which has been previously described as engulfment-dependent and hence as a possible murder. RESULTS: We found that B.al/rapaav is resistant to caspase-pathway activation: the caspase-mediated suicide pathway initiates the cell-death process but is insufficient to cause B.al/rapaav death without the subsequent assistance of engulfment. When the engulfing cell P12.pa is absent, other typically non phagocytic cells can display cryptic engulfment potential and facilitate this death. CONCLUSIONS: We term this death an "assisted suicide" and propose that assisted suicides likely occur in other organisms. The study of assisted suicides might provide insight into non-cell autonomous influences on cell death. Understanding the mechanism that causes B.al/rapaav to be resistant to activation of the caspase pathway might reveal the basis of differences in the sensitivity to apoptotic stimuli of tumor and normal cells, a key issue in the field of cancer therapeutics. PMID- 27185173 TI - Short-term clinical outcomes after off-pump coronary artery bypass grafting at a single Veterans Affairs Medical Center. AB - BACKGROUND: We retrospectively assessed the outcomes after coronary revascularization at a single Veterans Affairs Medical Center when a strategy of assigning higher risk patients to off-pump coronary artery bypass grafting (CABG) was employed. METHODS: Over a 5 year period all consecutive patients that underwent CABG at our VA Medical Center were assigned to a surgeon who either performs the CABG exclusively off-pump or to one who performed the CABG on-pump. The higher risk patients were assigned preferentially for off-pump revascularization. VASQIP (VA Hospitals Surgical Quality Improvement Program) data between 10/2007 and 12/2012 were retrospectively reviewed at our VA Medical Center and the short term outcomes were assessed. RESULTS: A total of 252 consecutive patients underwent off-pump CABG (n = 170) and on-pump CABG (n = 82). There were significantly more patients with low LVEF (<45 %; p = 0.008) and cerebrovascular disease in the off-pump group (p = 0.024). The number of patients smoking at the time of surgery was significantly higher in the off-pump group (p = 0.002) as well. The 30-day composite morbidity and mortality was 6 % for all CABG patients and significantly lower with off-pump vs. on-pump CABG (3.5 % vs. 11 %; p = 0.019). There were no conversions from off-pump to on-pump surgery. CONCLUSIONS: A selective strategy to direct higher risk patients towards an off pump revascularization yielded favorable outcomes in an unselected veteran population treated at a single VA Medical Center over a 5 year period. PMID- 27185175 TI - Changes on Adipose Tissue Distribution After Laparoscopic Roux-en-Y Gastric Bypass in Obese Gottingen Minipig. Effects on Glucose Metabolism. AB - BACKGROUND: The objective of the study was to assess Roux-en-Y independent-to weight metabolic effects on an obese Gottingen minipig. METHODS: Eleven castrated Gottingen minipigs were enrolled. Minipigs became obese after a 9-month period of experimental diet. The animals were then subjected to a laparoscopic Roux-en-Y gastric bypass (period P1) followed by 4 months of follow-up (period P2). During this last period, they were fed to maintain similar body weight to that observed at the day of surgery. Registered parameters during each period included biometric variables; abdominal adipose tissue (AT) distribution; lipid profile; HOMA-IR; and fasting plasma leptin, adiponectin, glucose, insulin and fructosamine. RESULTS: Two pigs were unable to complete the study due to postoperative complications. Four months after surgery, the body weight (kg) was maintained (P1 51.90 +/- 5.78 vs P2 51.47 +/- 5.68). On the contrary, intraperitoneal AT (p < 0.0001), glucose (mmol/L) (P1: 5.53 +/- 0.37 vs 4.66 +/- 0.72, p = 0.019), fructosamine (MUmol/L) (p = 0.0001) and insulin (pmol/L) (P1: 36.66 +/- 13.94 vs P2: 21.42 +/- 12.62, p = 0.001) significantly decreased after surgery. Lipid profile showed a significant increase after high-fat feeding period and a slight reduction at P2, which continued increasing. At the end of the study, leptin plasma levels (ng/mL) showed a significant reduction compared to basal value (p = 0.001). CONCLUSIONS: The improvement in glucose metabolism seems to occur by means of the redistribution of body fat. In order to fully confirm this hypothesis, more studies including the evaluation of incretins and inflammatory molecules, as well as a glycaemia control study against glucose load, are needed. PMID- 27185174 TI - Using short-message-service notification as a method to improve acute flaccid paralysis surveillance in Papua New Guinea. AB - BACKGROUND: High quality acute flaccid paralysis (AFP) surveillance is required to maintain polio-free status of a country. Papua New Guinea (PNG) is considered as one of the highest risk countries for polio re-importation and circulation in the Western Pacific Region (WPRO) of the World Health Organization due to poor healthcare infrastructure and inadequate performance in AFP surveillance. The Government of PNG, in collaboration with WHO, piloted the introduction of short message-service (SMS) to sensitize pediatricians and provincial disease control officers on AFP and to receive notification of possible AFP cases to improve surveillance quality in PNG. METHODS: Ninety six health care professionals were registered to receive SMS reminders to report any case of acute flaccid paralysis. Fourteen SMS messages were sent to each participant from September 2012 to November 2013. The number of reported AFP cases were compared before and after the introduction of SMS. RESULTS: Two hundred fifty three unique responses were received with an overall response rate of 21 %. More than 80 % of responses were reported within 3 days of sending the SMS. The number of reported AFP cases increased from 10 cases per year in 2009-2012 to 25 cases per year during the study period and correlated with provincial participation of the health care professionals. CONCLUSIONS: Combined with improved sensitization of health care professionals on AFP reporting criteria and sample collection, SMS messaging provides an effective means to increase timely reporting and improve the availability of epidemiologic information on polio surveillance in PNG. PMID- 27185176 TI - Results of Laparoscopic Sleeve Gastrectomy in 541 Consecutive Patients with Low Baseline Body Mass Index (30-35 kg/m2). AB - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is currently the leading bariatric procedure and targets, among other obesity classes, patients with BMI 30-35 kg/m2, which are reaching alarming proportions. METHODS: Between February 2010 and August 2015, data on 541 consecutive patients with BMI 30-35 kg/m2 undergoing LSG were prospectively collected and analyzed. RESULTS: Mean age was 32 +/- 8 years (13-65) and 419 (77.4 %) were women. Preoperative weight was 92.0 +/- 8.8 kg (65-121) and BMI was 32.6 +/- 1.5 kg/m2 (30-35). Comorbidities were detected in 210 (39 %) patients. Operative time was 74 +/- 12 min (40-110) and postoperative stay was 1.7 +/- 0.22 days (1-3). There were no deaths, leaks, abscesses or strictures and the rate of hemorrhage was 1.2 %. At 1 year, 98 % were followed and BMI decreased to 24.7 +/- 1.6, the percentage of total weight loss (% TWL) was 24.1 +/- 4.7 while the percentage of excess BMI loss (%EBMIL) reached 106.1 +/- 24.1. At 5 years, 76 % of followed patients achieved a >=50 % EBMIL. CONCLUSION: With appropriate surgical expertise, LSG in patients with BMI 30-35 kg/m2 achieved excellent outcomes with a zero fistula rate. PMID- 27185177 TI - Impact of Sleeve Gastrectomy on Type 2 Diabetes Mellitus, Gastric Emptying Time, Glucagon-Like Peptide 1 (GLP-1), Ghrelin and Leptin in Non-morbidly Obese Subjects with BMI 30-35.0 kg/m2: a Prospective Study. AB - BACKGROUND: The study was conducted to evaluate the impact of laparoscopic sleeve gastrectomy (LSG) on type 2 diabetes mellitus (T2DM) in patients with a body mass index (BMI) of 30.0-35.0 kg/m2. Possible mechanisms, including alterations in gastric emptying time (GET), glucagon-like peptide 1 (GLP-1), ghrelin and leptin, were evaluated. METHODS: Twenty obese patients with T2DM and with a BMI of 30.0 35.0 kg/m2 underwent LSG during March 2012 to February 2015. Glycosylated haemoglobin (HbA1c), fasting plasma glucose (FPG) and GET were measured at baseline, 3 months, 6 months, 12 months and 24 months after surgery. Fasting and post-prandial levels of serum GLP-1, ghrelin and leptin were measured pre operatively and after 3 and 6 months. RESULTS: The average duration of follow-up was 17.6 months, and 10 patients had completed 2 years of follow-up. After 2 years, the average BMI decreased from 33.4 +/- 1.2 to 26.7 +/- 1.8 kg/m2. The mean HbA1c decreased from 8.7 +/- 1.6 to 6.7 +/- 1.5 %, respectively. Ten patients achieved complete remission. Insulin could be stopped in all six patients who were on it pre-operatively. Meal-stimulated GLP-1 response and serum insulin at 30 min showed a significant increase following surgery. There was a significant decrease in GET. CONCLUSIONS: This prospective study confirms the positive impact of LSG on diabetic status of non-morbidly obese patients. The possible mechanisms include the rise in post-prandial GLP-1 level induced by accelerated gastric emptying, leading to an increase in insulin secretion. LSG also leads to decreased ghrelin and leptin levels which may have a role in improving glucose homeostasis after surgery. PMID- 27185178 TI - Usefulness of transcutaneous PCO2 to assess nocturnal hypoventilation in restrictive lung disorders. AB - BACKGROUND AND OBJECTIVE: Nocturnal hypoventilation is now an accepted indication for the initiation of non-invasive ventilation. Nocturnal hypoventilation may be an under diagnosed condition in chronic respiratory failure. The most appropriate strategy to identify sleep hypoventilation is not yet clearly defined. In clinical practice, it is indirectly assessed using nocturnal pulse oximetry (NPO) and morning arterial blood gases (mABG). Even though continuous transcutaneous carbon dioxide partial pressure (TcPCO2 ) monitoring is theoretically superior to NPO plus mABG, it is not routinely used. We aimed to prospectively compare NPO plus mABG with nocturnal TcPCO2 for the detection of alveolar hypoventilation in a cohort of patients with chronic restrictive respiratory dysfunction. METHODS: We assessed 80 recordings of mABG, nocturnal TcPCO2 and NPO in 72 consecutive patients with neuromuscular disease or thoracic cage disorders. Nocturnal hypoventilation was defined as a mean nightime TcPCO2 >=50 mm Hg, and nocturnal hypoxaemia as >=30% of the night with transcutaneous pulse oxygen saturation <=90% and/or >5 consecutive minutes with transcutaneous pulse oxygen saturation <=88%. RESULTS: Amongst the 80 recordings, 25 of 76 (32.9%) without nocturnal hypoxaemia and 16 of 59 (27.1%) without hypercapnia on mABG showed nocturnal hypoventilation on TcPCO2 . Amongst recordings showing both normal NPO and mABG, 16 of 52 (30.8%) had a mean TcPCO2 >=50 mm Hg. Nocturnal hypoxaemia was associated with nocturnal hypoventilation in all recordings. However, 5 of 21 (23.8%) recordings that showed an absence of nocturnal hypoventilation at the chosen threshold showed hypercapnia on mABG. CONCLUSION: Morning arterial blood gases and NPO alone or in combination underestimate nocturnal hypoventilation in patients with chronic restrictive respiratory dysfunction of extrapulmonary origin. PMID- 27185179 TI - Effects of additional anterior body mass on gait. AB - BACKGROUND: Gradual increases in mass such as during pregnancy are associated with changes in gait at natural velocities. The purpose of this study was to examine how added mass at natural and imposed slow walking velocities would affect gait parameters. METHODS: Eighteen adult females walked at two velocities (natural and 25 % slower than their natural pace) under four mass conditions (initial harness only (1 kg), 4.535 kg added anteriorly, 9.07 kg added anteriorly, and final harness only (1 kg)). We collected gait kinematics (100 Hz) using a motion capture system. RESULTS: Added anterior mass decreased cycle time and stride length. Stride width decreased once the mass was removed (p < .01). Added mass resulted in smaller peak hip extension angles (p < .01). The imposed slow walking velocity increased cycle time, double limb support time and decreased stride length, peak hip extension angles, and peak plantarflexion angles (p < .01). With added anterior mass and an imposed slow walking velocity, participants decreased cycle time when mass was added and increased cycle time once the mass was removed (p < .01). CONCLUSIONS: Gait adaptations may be commensurate with the magnitude of additional mass when walking at imposed slow versus natural velocities. This study presents a method for understanding how increased mass and imposed speed might affect gait independent of other effects related to pregnancy. Examining how added body mass and speed influence gait is one step in better understanding how women adapt to walking under different conditions. PMID- 27185180 TI - Role of yttrium-90 in the management of unresectable hepatocellular carcinoma and hepatic metastases. AB - BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is the sixth most common cancer and third leading cause of cancer-related death in the world. The management of unresectable HCC and hepatic metastases from various solid tumors is a clinical dilemma. There is paucity of data on the treatment of unresectable HCC and hepatic metastases with yttrium-90 (90Y) radioembolization. METHODS: Thirty patients (mean age; 55.2 years; range 43-82 years) comprising 21 patients with HCC (12 patients have cirrhosis of which 3 patients belong to Child-Pugh class A and 9 patients belong to Child-Pugh class B), 7 patients with metastasis from colorectal cancer, 1 patient with metastasis from melanoma, and 1 patient with metastasis from ovarian carcinoma underwent resin-based 90Y radioembolization between 2013 and 2015 in our study. In all the patients, after embolization of non-target vasculature, SPECT and planar scintigraphy were done with the injection of 5-6 mCi (185-222 MBq) of 99mTc-labeled macroaggregated albumin (MAA) into the hepatic artery. Then, lung shunt fraction was assessed and dose was calculated based on body surface area (BSA) method for SIR-Spheres. Post therapeutic 90Y bremsstrahlung SPECT and 90Y PET was performed within 30 hours following therapy to see the hepatic and extrahepatic distribution of spheres. Side effects following therapy were noted in all the patients. All patients were followed up with triphasic CT liver 3 months following therapy. Therapeutic response was evaluated with necrosis criteria used for therapy response assessment in solid tumors. RESULTS: On follow up, 14 patients (46 %) developed minor side effects following treatment and resolved without active intervention. The most common side effects include mild abdominal pain in 11 patients (36 %), nausea in 8 patients (26 %), and fatigue in 6 patients (20 %). On follow up imaging at 3 months following treatment, a complete response was observed in two patients (7 %), partial response in seven patients (23 %), stable disease in 15 patients (50 %), and progressive disease in six patients (20 %). CONCLUSION: This study provides supportive evidence of the safety and efficacy on 90Y radioembolization for the treatment of unresectable HCC and hepatic metastases from various solid tumors. 90Y PET is a better radionuclide technique for assessing the hepatic and extrahepatic distribution of spheres following therapy compared to 90Y Bremsstrahlung SPECT. Thus, 90Y radioembolization is proving to be promising treatment with average disease control rates around 80 % and should be widely utilized. PMID- 27185181 TI - Influence of coumarin and some coumarin derivatives on serum lipid profiles in carbontetrachloride-exposed rats. AB - In the present study, coumarin and some coumarin derivatives (esculetin, scoparone, and 4-methylumbelliferone) were investigated for their lipid-lowering effect in rats. Male Sprague-Dawley rats (150-200 g) were divided into six groups and each group comprised of five rats. Hepatic injury-dependent hyperlipidemia was induced by carbon tetrachloride (CCl4, 1.25 ml/kg). Coumarin and coumarin derivatives esculetin (35 mg/kg), scoparone (35 mg/kg), 4-methylumbelliferone (35 mg/kg), or coumarin (30 mg/kg) were administered to experimental groups at 12-h intervals. Animals received the derivatives esculetin, scoparone or 4 methylumbelliferone prior to the administration of a single toxic dose of CCl4. Serum total cholesterol (TC), triglyceride (TG), very low-density lipoprotein cholesterol (VLDL-C), and low-density lipoprotein cholesterol (LDL-C) levels significantly increased in CCl4-treated group ( p < 0.05, p < 0.01, p < 0.01, and p < 0.05, respectively), while levels of serum high-density lipoprotein cholesterol (HDL-C) decreased ( p < 0.01). 4-Methylumbelliferone had no recovery effects on serum TC levels, however, significantly prevented CCl4-induced hyperlipidemia by reducing TG and VLDL-C levels ( p < 0.05 and p < 0.05, respectively). In addition, coumarin had no recovery effect on any of the serum lipid parameters against CCl4-induced hyperlipidemia. Among the coumarin derivatives only esculetin and scoparone significantly prevented serum HDL-C in CCl4-induced dyslipidemia. The results from this study indicate that the chemical structure of coumarins plays an important role on the regulation of serum lipid profiles. PMID- 27185182 TI - Comparative transcriptome analysis revealing dormant conidia and germination associated genes in Aspergillus species: an essential role for AtfA in conidial dormancy. AB - BACKGROUND: Fungal conidia are usually dormant unless the extracellular conditions are right for germination. Despite the importance of dormancy, little is known about the molecular mechanism underlying entry to, maintenance of, and exit from dormancy. To gain comprehensive and inter-species insights, transcriptome analyses were conducted across Aspergillus fumigatus, Aspergillus niger, and Aspergillus oryzae. RESULTS: We found transcripts of 687, 694, and 812 genes were enriched in the resting conidia compared with hyphae in A. fumigatus, A. niger, and A. oryzae, respectively (conidia-associated genes). Similarly, transcripts of 766, 1,241, and 749 genes were increased in the 1 h-cultured conidia compared with the resting conidia (germination-associated genes). Among the three Aspergillus species, we identified orthologous 6,172 genes, 91 and 391 of which are common conidia- and germination-associated genes, respectively. A variety of stress-related genes, including the catalase genes, were found in the common conidia-associated gene set, and ribosome-related genes were significantly enriched among the germination-associated genes. Among the germination-associated genes, we found that calA-family genes encoding a thaumatin-like protein were extraordinary expressed in early germination stage in all Aspergillus species tested here. In A. fumigatus 63 % of the common conidia-associated genes were expressed in a bZIP-type transcriptional regulator AtfA-dependent manner, indicating that AtfA plays a pivotal role in the maintenance of resting conidial physiology. Unexpectedly, the precocious expression of the germination-associated calA and an abnormal metabolic activity were detected in the resting conidia of the atfA mutant, suggesting that AtfA was involved in the retention of conidial dormancy. CONCLUSIONS: A comparison among transcriptomes of hyphae, resting conidia, and 1 h-grown conidia in the three Aspergillus species revealed likely common factors involved in conidial dormancy. AtfA positively regulates conidial stress-related genes and negatively mediates the gene expressions related to germination, suggesting a major role for AtfA in Aspergillus conidial dormancy. PMID- 27185184 TI - Trends in the epidemiology of head and neck cancer in London. AB - BACKGROUND: Head and neck cancers [HNCs] are biologically heterogeneous tumours. The objectives of this study were to describe trends in incidence of HNCs amongst London residents by sex, age, anatomical site, deprivation and ethnicity. METHODS: Annual age-standardised incidence rates [ASRs] were calculated on HNC registration data, overall and for specific cancer sites, by sex and morphology (1985-2010) and area-based socio-economic deprivation score (2006-2010). Age standardised incidence rate ratios [IRRs] for the main ethnic groups were calculated by cancer site, using White males and females as the reference groups (1998-2009). RESULTS: The ASR of HNC in males increased by 40% from 17.3 [95% CI: 15.8-18.6] to 24.2 [95% CI: 22.5-25.8] per 100 000 and in females by 87% from 7.0 [95% CI: 6.2-7.8] to 13.1 [95% CI: 11.9-14.2] per 100 000. Seventy-three per cent of cases spanned four cancer sites: larynx, thyroid, oral and oropharynx. Larynx was most common (23%), and had the highest male: female ratio (6 : 1); ASRs decreased significantly over time, most notably in males [P < 0.001]. Oral cavity was the second most common (21%), with a male: female ratio of 2 : 1, and increasing ASRs in both sexes [P < 0.001]. The majority of cases were male (64%) and from deprived areas (59%). Deprivation was associated with a significantly higher incidence for larynx (males), oropharynx (males and females) and oral cavity (females) [P < 0.05]. The age-specific rate for middle-aged adults (45-64 years) was high for oropharyngeal cancer. The incidence of thyroid cancers increased significantly in both sexes [P < 0.001], and this was the only site more common in females. One in five cases with known ethnicity was from a non White group (20%). Compared with their White counterparts, Bangladeshi females had a higher incidence of oral, laryngeal and thyroid cancers; Chinese males and females had a higher incidence of nasopharyngeal cancer; and Pakistani and Indian females and Indian males also had higher incidence of oral cancer. CONCLUSIONS: HNCs are increasing in London males and females with significant variation by cancer site over time; oral and oropharyngeal cancers show the most significant rise, with implications for public health action and service provision. PMID- 27185185 TI - Commentary on: Prevention of postoperative bile leakage using an omental plugging technique for subtotal cholecystectomy in the "difficult gallbladder". PMID- 27185183 TI - Nosocomial rotavirus infection: An up to date evaluation of European studies. AB - Rotavirus (RV) is worldwide considered as the most important viral agent of acute gastroenteritis in children less than 5 y. Since 2006, the availability of anti RV vaccines has deeply modified the incidence and economic burden of RV infection. In Europe, some countries have introduced an anti-RV vaccination program in the last 10 y. Although community acquired RV (CARV) disease is the most studied condition of RV infection, recently some authors have highlighted the importance of nosocomial RV (nRV) disease as an emerging public health issue. The aim of this review is to summarize the epidemiology of both CARV and nRV, in order to discuss the difficulty of a clear evaluation of the burden of the disease in absence of comparable data. In particular, we focused our attention to European studies regarding nRV in terms of divergences related to definition, report of incidence rate and methodological issues. PMID- 27185188 TI - Bridges between mitochondrial oxidative stress, ER stress and mTOR signaling in pancreatic beta cells. AB - Pancreatic beta cell dysfunction, i.e., failure to provide insulin in concentrations sufficient to control blood sugar, is central to the etiology of all types of diabetes. Current evidence implicates mitochondrial oxidative stress and endoplasmic reticulum (ER) stress in pancreatic beta cell loss and impaired insulin secretion. Oxidative and ER stress are interconnected so that misfolded proteins induce reactive oxygen species (ROS) production; likewise, oxidative stress disturbs the ER redox state thereby disrupting correct disulfide bond formation and proper protein folding. mTOR signaling regulates many metabolic processes including protein synthesis, cell growth, survival and proliferation. Oxidative stress inhibits mTORC1, which is considered an important suppressor of mitochondrial oxidative stress in beta cells, and ultimately, controls cell survival. The interplay between ER stress and mTORC1 is complicated, since the unfolded protein response (UPR) activation can occur upstream or downstream of mTORC1. Persistent activation of mTORC1 initiates protein synthesis and UPR activation, while in the later phase induces ER stress. Chronic activation of ER stress inhibits Akt/mTORC1 pathway, while under particular settings, acute activation of UPR activates Akt-mTOR signaling. Thus, modulating mitochondrial oxidative stress and ER stress via mTOR signaling may be an approach that will effectively suppress obesity- or glucolipotoxicity-induced metabolic disorders such as insulin resistance and type 2 diabetes mellitus (T2DM). In this review, we focus on the regulations between mTOR signaling and mitochondrial oxidative or ER stress in pancreatic beta cells. PMID- 27185187 TI - Phosphorylated heat shock protein 27 promotes lipid clearance in hepatic cells through interacting with STAT3 and activating autophagy. AB - Nonalcoholic fatty liver disease (NAFLD) has become the major liver disease worldwide. Recently, several studies have identified that the activation of autophagy attenuates hepatic steatosis. Heat shock protein 27 (Hsp27) is involved in autophagy in response to various stimuli. In this study, we demonstrate that phosphorylated Hsp27 stimulates autophagy and lipid droplet clearance and interacts with STAT3. In vivo study showed that high fat diet (HFD) feeding increased Hsp25 (mouse orthology of Hsp27) phosphorylation and autophagy in mouse livers. Inhibition of Hsp25 phosphorylation exacerbated HFD-induced hepatic steatosis in mice. In vitro study showed that palmitate-induced lipid overload in hepatic cells was enhanced by Hsp27 knockdown, KRIBB3 treatment and Hsp27-3A (non phosphorylatable) overexpression but was prevented by Hsp27-WT (wild type) and Hsp27-3D (phosphomimetic) overexpression. Mechanism analysis demonstrated that palmitate could induce Hsp27 phosphorylation which promoted palmitate-induced autophagy. Phosphorylated Hsp27 interacted with STAT3 in response to palmitate treatment, and disrupted the STAT3/PKR complexes, facilitated PKR-dependent eIF2alpha phosphorylation, and thus stimulated autophagy. To conclude, our study provides a novel mechanism by which the phosphorylated Hsp27 promotes hepatic lipid clearance and suggests a new insight for therapy of steatotic diseases such as nonalcoholic fatty liver disease (NAFLD). PMID- 27185189 TI - Ecology of conflict: marine food supply affects human-wildlife interactions on land. AB - Human-wildlife conflicts impose considerable costs to people and wildlife worldwide. Most research focuses on proximate causes, offering limited generalizable understanding of ultimate drivers. We tested three competing hypotheses (problem individuals, regional population saturation, limited food supply) that relate to underlying processes of human-grizzly bear (Ursus arctos horribilis) conflict, using data from British Columbia, Canada, between 1960 2014. We found most support for the limited food supply hypothesis: in bear populations that feed on spawning salmon (Oncorhynchus spp.), the annual number of bears/km(2) killed due to conflicts with humans increased by an average of 20% (6-32% [95% CI]) for each 50% decrease in annual salmon biomass. Furthermore, we found that across all bear populations (with or without access to salmon), 81% of attacks on humans and 82% of conflict kills occurred after the approximate onset of hyperphagia (July 1(st)), a period of intense caloric demand. Contrary to practices by many management agencies, conflict frequency was not reduced by hunting or removal of problem individuals. Our finding that a marine resource affects terrestrial conflict suggests that evidence-based policy for reducing harm to wildlife and humans requires not only insight into ultimate drivers of conflict, but also management that spans ecosystem and jurisdictional boundaries. PMID- 27185190 TI - Towards medicinal mechanochemistry: evolution of milling from pharmaceutical solid form screening to the synthesis of active pharmaceutical ingredients (APIs). AB - This overview highlights the emergent area of mechanochemical reactions for making active pharmaceutical ingredients (APIs), and covers the latest advances in the recently established area of mechanochemical screening and synthesis of pharmaceutical solid forms, specifically polymorphs, cocrystals, salts and salt cocrystals. We also provide an overview of the most recent developments in pharmaceutical uses of mechanochemistry, including real-time reaction monitoring, techniques for polymorph control and approaches for continuous manufacture using twin screw extrusion, and more. Most importantly, we show how the overlap of previously unrelated areas of mechanochemical screening for API solid forms, organic synthesis by milling, and mechanochemical screening for molecular recognition, enables the emergence of a new research discipline in which different aspects of pharmaceutical and medicinal chemistry are addressed through mechanochemistry rather than through conventional solution-based routes. The emergence of such medicinal mechanochemistry is likely to have a strong impact on future pharmaceutical and medicinal chemistry, as it offers not only access to materials and reactivity that are sometimes difficult or even impossible to access from solution, but can also provide a general answer to the demands of the pharmaceutical industry for cleaner, safer and efficient synthetic solutions. PMID- 27185186 TI - Myofibril growth during cardiac hypertrophy is regulated through dual phosphorylation and acetylation of the actin capping protein CapZ. AB - The mechanotransduction signaling pathways initiated in heart muscle by increased mechanical loading are known to lead to long-term transcriptional changes and hypertrophy, but the rapid events for adaptation at the sarcomeric level are not fully understood. The goal of this study was to test the hypothesis that actin filament assembly during cardiomyocyte growth is regulated by post-translational modifications (PTMs) of CapZbeta1. In rapidly hypertrophying neonatal rat ventricular myocytes (NRVMs) stimulated by phenylephrine (PE), two-dimensional gel electrophoresis (2DGE) of CapZbeta1 revealed a shift toward more negative charge. Consistent with this, mass spectrometry identified CapZbeta1 phosphorylation on serine-204 and acetylation on lysine-199, two residues which are near the actin binding surface of CapZbeta1. Ectopic expression of dominant negative PKCE (dnPKCE) in NRVMs blunted the PE-induced increase in CapZ dynamics, as evidenced by the kinetic constant (Kfrap) of fluorescence recovery after photobleaching (FRAP), and concomitantly reduced phosphorylation and acetylation of CapZbeta1. Furthermore, inhibition of class I histone deacetylases (HDACs) increased lysine-199 acetylation on CapZbeta1, which increased Kfrap of CapZ and stimulated actin dynamics. Finally, we show that PE treatment of NRVMs results in decreased binding of HDAC3 to myofibrils, suggesting a signal-dependent mechanism for the regulation of sarcomere-associated CapZbeta1 acetylation. Taken together, this dual regulation through phosphorylation and acetylation of CapZbeta1 provides a novel model for the regulation of myofibril growth during cardiac hypertrophy. PMID- 27185191 TI - Comparison between flipped classroom and team-based learning in fixed prosthodontic education. AB - PURPOSE: We previously investigated the effects of team-based learning (TBL) on fixed prosthodontic education and reported that TBL could have higher efficiency with high student satisfaction than traditional lecture. In the current report, we introduced flipped classroom to the fixed prosthodontic education and compared their effectiveness based on the final examination score in addition to TBL. METHODS: Participants were 41 students from Tokushima University School of Dentistry who attended a fixed prosthodontics course. The first six classes adopted the flipped classroom style while the latter eight classes adopted TBL. To evaluate the relationship between learning styles and their effectiveness, we compared results from the term-end examination between the curriculum covered by flipped classroom and TBL-style classes. To draw comparisons, a referential examination with the same questions was conducted to eight faculty members who had not attended any of these classes. RESULTS: Term-end examination results showed that TBL classes had slightly higher scores than flipped classroom classes. Referential examination results also showed higher scores for the same curriculum and no significant interaction was found between class formats and the term-end and referential examination scores. Analysis revealed no noticeable difference in the effectiveness of the class formats. CONCLUSION: Our previous study reported that TBL had higher efficiency than traditional style lecture. In the current study, there was no statistical difference in the examination score between flipped classroom and TBL. Therefore, we conclude that both styles are highly effective than traditional style lecture and constitute valid formats for clinical dental education. PMID- 27185192 TI - Development of phytotoxicity indexes and their correlation with ecotoxicological, stability and physicochemical parameters during passive composting of poultry manure. AB - Both raw and composted poultry manure is applied as soil amendment. The aims of this study were: (1) to develop phytotoxicity indexes for organic wastes and composts, and (2) to assess the correlation among phytotoxicity indexes, ecotoxicological endpoints and stability and physicochemical parameters during passive composting of poultry manure. Six 2-m(3) composting piles were constructed and four parameter groups (physicochemical and microbiological parameters, ecotoxicological endpoints, and biological activity) were determined at four sampling times during 92days. Extracts were used to carry out acute toxicity tests on Daphnia magna, Lactuca sativa and Raphanus sativus. Composting decreased average toxicity 22.8% for the 3 species and D. magna was the most sensitive species. The static respiration index decreased from 1.12 to 0.46mgO2gOMh(-1) whilst organic matter reduced by 64.1% at the end of the process. Escherichia coli colonies remained higher than values recommended by international guidelines. The D. magna immobilization test allowed the assessment of possible leachate or run-off toxicity. The new phytotoxicity indexes (RGIC0.8 and GIC80%), proposed in this study, as well as salinity, proved to be good maturity indicators. Hence, these phytotoxicity indexes could be implemented in monitoring strategies as useful ecotoxicological tools. Multivariate analyses demonstrated positive correlations between ecotoxicological endpoints (low toxicity) and biological activity (stability). These two parameter groups were associated at the final sampling time and showed negative correlations with several physicochemical parameters (organic and inorganic contents). The final poultry manure compost was rendered stable, but immature and, thus, unsuitable for soil amending. PMID- 27185193 TI - Management of acute heart failure in elderly patients. AB - Acute heart failure (AHF) is the most common cause of unplanned hospital admissions, and is associated with high mortality rates. Over the next few decades, the combination of improved cardiovascular disease survival and progressive ageing of the population will further increase the prevalence of AHF in developed countries. New recommendations on the management of AHF have been published recently, but as elderly patients are under-represented in clinical trials, and scientific evidence is often lacking, the diagnosis and management of AHF in this population is challenging. The clinical presentation of AHF, especially in patients aged>85years, differs substantially from that in younger patients, with unspecific symptoms, such as fatigue and confusion, often overriding dyspnoea. Older patients also have a different risk profile compared with younger patients: often heart failure with preserved ejection fraction, and infection as the most frequent precipitating factor of AHF. Moreover, co morbidities, disability and frailty are common, and increase morbidity, recovery time, readmission rates and mortality; their presence should be detected during a geriatric assessment. Diagnostics and treatment for AHF should be tailored according to cardiopulmonary and geriatric status, giving special attention to the patient's preferences for care. Whereas many elderly AHF patients may be managed similarly to younger patients, different strategies should be applied in the presence of relevant co-morbidities, disability and frailty. The option of palliative care should be considered at an early stage, to avoid unnecessary and harmful diagnostics and treatments. PMID- 27185195 TI - Classical-Reaction-Driven Stereo- and Regioselective C(sp(3) )-H Functionalization of Aliphatic Amines. AB - A large variety of synthetic methods have been developed for the synthesis of functionalized aliphatic amines because of their broad spectrum of application. Metallic reagents/catalysts and/or toxic oxidants are involved in most of the cases. Direct C?H functionalization of aliphatic amines via their classical condensation reactions with suitable carbonyl compounds is advantageous because this method avoids hazardous metallic reagents, toxic oxidants and pre activation/pre-functionalization step(s). In this account, the concept of direct C?H functionalization of aliphatic amines based on the classical condensation isomerization-addition (CIA) strategy followed by recent contributions from our ongoing research in the field along with relevant examples from other groups are described. Successes in stereo- and regioselective C?C and C?O bond formation via direct alpha- as well as beta-C(sp(3) )-H functionalization are discussed. PMID- 27185194 TI - Deep Patient: An Unsupervised Representation to Predict the Future of Patients from the Electronic Health Records. AB - Secondary use of electronic health records (EHRs) promises to advance clinical research and better inform clinical decision making. Challenges in summarizing and representing patient data prevent widespread practice of predictive modeling using EHRs. Here we present a novel unsupervised deep feature learning method to derive a general-purpose patient representation from EHR data that facilitates clinical predictive modeling. In particular, a three-layer stack of denoising autoencoders was used to capture hierarchical regularities and dependencies in the aggregated EHRs of about 700,000 patients from the Mount Sinai data warehouse. The result is a representation we name "deep patient". We evaluated this representation as broadly predictive of health states by assessing the probability of patients to develop various diseases. We performed evaluation using 76,214 test patients comprising 78 diseases from diverse clinical domains and temporal windows. Our results significantly outperformed those achieved using representations based on raw EHR data and alternative feature learning strategies. Prediction performance for severe diabetes, schizophrenia, and various cancers were among the top performing. These findings indicate that deep learning applied to EHRs can derive patient representations that offer improved clinical predictions, and could provide a machine learning framework for augmenting clinical decision systems. PMID- 27185196 TI - Tantalum implanted entangled porous titanium promotes surface osseointegration and bone ingrowth. AB - Porous Ti is considered to be an ideal graft material in orthopaedic and dental surgeries due to its similar spatial structures and mechanical properties to cancellous bone. In this work, to overcome the bioinertia of Ti, Ta-implanted entangled porous titanium (EPT) was constructed by plasma immersion ion implantation &deposition (PIII&D) method. Ca-implanted and unimplanted EPTs were investigated as control groups. Although no difference was found in surface topography and mechanical performances, both Ca- and Ta-implanted groups had better effects in promoting MG-63 cell viability, proliferation, differentiation, and mineralization than those of unimplanted group. The expression of osteogenic related markers examined by qRT-PCR and western blotting was upregulated in Ca- and Ta-implanted groups. Moreover, Ta-implanted EPT group could reach a higher level of these effects than that of Ca-implanted group. Enhanced osseointegration of both Ca- and Ta-implanted EPT implants was demonstrated through in vivo experiments, including micro-CT evaluation, push-out test, sequential fluorescent labeling and histological observation. However, the Ta-implanted group possessed more stable and continuous osteogenic activity. Our results suggest that Ta implanted EPT can be developed as one of the highly efficient graft material for bone reconstruction situations. PMID- 27185197 TI - Phase II trial of ofatumumab plus ESHAP (O-ESHAP) as salvage treatment for patients with relapsed or refractory classical Hodgkin lymphoma after first-line chemotherapy. AB - The management of recurrent/refractory (R/R) Hodgkin lymphoma (HL) remains challenging. Previously published data have shown some efficacy of rituximab in this setting. The purpose of this phase II trial was to investigate the activity of ofatumumab in combination with etoposide, steroids, cytarabine and cisplatin (O-ESHAP) in 62 patients with R/R classical HL. Treatment consisted of ESHAP plus ofatumumab 1000 mg on days 1 and 8 of the first cycle and day 1 of the second and third cycles. O-ESHAP was well tolerated with only 3% of patients requiring treatment discontinuation because of adverse events. Overall response rate was 73% (44% complete metabolic response). In multivariate analysis, early relapse (P < 0.001), bulky disease (P < 0.001) and B symptoms (P < 0.001) were the most important prognostic factors for response. No failures of stem cell mobilization were observed. The high response rate, particularly the complete metabolic response rate, the low toxicity profile, and the high mobilizing potential of the O-ESHAP regimen suggest that patients with R/R HL may benefit from this salvage regimen. However, with the encouraging results observed with other new therapeutic agents in HL, the O-ESHAP regimen could be restricted to patients failing these agents or to those with R/R nodular lymphocyte-predominant HL. PMID- 27185198 TI - Functional evaluation of TERT-CLPTM1L genetic variants associated with susceptibility of papillary thyroid carcinoma. AB - TERT is the catalytic subunit of telomerase which plays an essential part in cellular immortality by maintaining telomere integrity. TERT is commonly over expressed in human malignancies, indicating its key role in cell transformation. The chromosome 5p15.33 TERT-CLPTM1L region has been associated with susceptibility of multiple cancers via a genome-wide association approach. However, the involvement of this locus in papillary thyroid carcinoma (PTC) etiology is still largely unknown. We analyzed 15 haplotype-tagging single nucleotide polymorphisms (htSNPs) of the TERT-CLPTM1L region in a two stage case control design. After genotyping 2300 PTC patients and frequency-matched 2300 unaffected controls, we found that TERT rs2736100 genetic variant is significantly associated with elevated PTC risk. Ex vivo reporter gene assays indicated that the PTC susceptibility rs2736100 polymorphism locating in a potential TERT intronic enhancer has a genotype-specific effect on TERT expression. Correlations between rs2736100 genotypes and tissue-specific TERT expression supported the regulatory function of this genetic variant in vivo. Our data demonstrated that the functional TERT rs2736100 SNP as a novel genetic component of PTC etiology. This study, together with recent studies in other cancers, unequivocally establishes an essential role of TERT in cancers. PMID- 27185199 TI - Rapid approximate calculation of water binding free energies in the whole hydration domain of (bio)macromolecules. AB - The evaluation of water binding free energies around solute molecules is important for the thermodynamic characterization of hydration or association processes. Here, a rapid approximate method to estimate water binding free energies around (bio)macromolecules from a single molecular dynamics simulation is presented. The basic idea is that endpoint free-energy calculation methods are applied and the endpoint quantities are monitored on a three-dimensional grid around the solute. Thus, a gridded map of water binding free energies around the solute is obtained, that is, from a single short simulation, a map of favorable and unfavorable water binding sites can be constructed. Among the employed free energy calculation methods, approaches involving endpoint information pertaining to actual thermodynamic integration calculations or endpoint information as exploited in the linear interaction energy method were examined. The accuracy of the approximate approaches was evaluated on the hydration of a cage-like molecule representing either a nonpolar, polar, or charged water binding site and on alpha and beta-cyclodextrin molecules. Among the tested approaches, the linear interaction energy method is considered the most viable approach. Applying the linear interaction energy method on the grid around the solute, a semi quantitative thermodynamic characterization of hydration around the whole solute is obtained. Disadvantages are the approximate nature of the method and a limited flexibility of the solute. (c) 2016 Wiley Periodicals, Inc. PMID- 27185200 TI - Collection and immunoselection of CD34+ cells: the impact of age, sex, and diabetes in patients with chronic heart failure. AB - BACKGROUND: Mobilized peripheral blood is the most common source of CD34+ cells intended for transplantations. The collection and enrichment of CD34+ cells could be affected by various factors and there are some controversies regarding the effects of patient-related factors. The aim of this study was to assess the impact of age, sex, and diabetes on the CD34+ cell grafts in patients with chronic heart failure. STUDY DESIGN AND METHODS: Cell grafts from 100 adult patients scheduled for autologous CD34+ cell transplantation were investigated. The CD34+ cells were collected using leukapheresis after granulocyte-colony stimulating factor mobilization and further enriched using the immunomagnetic CD34+ selection. The number of CD34+ cells and their viability were determined by flow cytometry. RESULTS: Older patients had significantly lower CD34+ cell counts than younger patients. The differences between men and women were not found. There was a trend toward an inverse relationship between diabetes and the CD34+ cell count, however, without any significance. No differences in the CD34+ cell viability (97.6% before and 97.9% after selection) were found. The mean CD34+ cell recovery was 59.7% and was not statistically different between age groups, sex, and diabetic patients. CONCLUSION: Before the CD34+ cells are collected the patient's age should be considered. The study did not demonstrate a significant impact of sex and diabetes on the CD34+ cell count. While age and sex did not affect the immunoselection process, diabetes slightly reduced cell recovery. Cell viabilities before and after the cell enrichment were comparable between the tested samples. PMID- 27185201 TI - To what extent do the presentation of fetus, amniotic fluid index and fetal weight at term affect the cardiac axis? AB - OBJECTIVE: To analyse the change in cardiac axis with advancing gestational age and the factors that may affect it. METHODS: 45 healthy pregnant women in 20th weeks of gestation were enrolled to the study. The cardiac axis was noted for each participant. The same group was once more assessed at term and the change in cardiac axis was calculated with the difference of cardiac axis at term and the 20th gestational weeks. Change in cardiac axis with advancing gestational weeks and factors that may affect it such as amniotic fluid index (AFI), estimated fetal weight (EFW) at term, actual birth weight and presentation of the fetus at term were evaluated. RESULTS: The median of ages was 28.0 (IQR=12.0)years within a range of 18-39years. The median of change in cardiac axis was 11.0 (IQR=9.0) degrees within a range of 3.0-47.0 degrees. The change in cardiac axis in regard to the fetal presenting part was 11.0 (IQR=8.0) degrees in vertex presentation and 23.50 (IQR=21.0) degrees in breech presentation. 81.1% of the variation in change in cardiac axis was found to be due to the actual birth weight and fetal presentation, with each 100g increase in actual birth weight leads to an increase of 0.375 degrees in cardiac axis. CONCLUSION: EFW at term, presentation of the fetus and the actual birth weight were all found to be significant in predicting the change in cardiac axis, but not AFI. These findings may have future potential value in evaluating electrocardiogram (ECG), especially of pregnants with extremes of left axis deviation (polyhydramnios, large fetus or breech presentation). Clinicians should be cautious during the interpretation of the ECG in pregnants, especially in those with extremes of left axis deviation because of either polyhydramnios, large fetus or breech presentation. PMID- 27185202 TI - Heavy chain (LvH) and light chain (LvL) of lipovitellin (Lv) of zebrafish can both bind to bacteria and enhance phagocytosis. AB - Lipovitellin (Lv) is an apoprotein in oviparous animals. Lv consists of a heavy chain (LvH) and a light chain (LvL) which are traditionally regarded as energy reserves for developing embryos. Recently, Lv has been shown to be involved in immune defense of developing embryos in fish. However, it remains unknown if each of LvH and LvL possesses immune activity; and if so, whether or not they function similarly. Here we clearly demonstrated that recombinant LvH (rLvH) and LvL (rLvL) from zebrafish vg1 gene bound to both the Gram-negative bacteria Escherichia coli and Vibrio anguillarum and the Gram-positive bacteria Staphylococcus aureus and Micrococcus luteus as well as the pathogen-associated molecular patterns LPS, LTA and PGN. In addition, both rLvH and rLvL were able to enhance the phagocytosis of bacteria E. coli and S. aureus by macrophages. All these data suggest that both LvH and LvL, in addition to being energy reserves, are also maternal immune-relevant factors capable of interacting with invading bacteria in zebrafish embryos/larvae. PMID- 27185203 TI - Identification and characterization of a constitutively expressed Ctenopharyngodon idella ADAR1 splicing isoform (CiADAR1a). AB - As one member of ADAR family, ADAR1 (adenosine deaminase acting on RNA 1) can convert adenosine to inosine within dsRNA. There are many ADAR1 splicing isoforms in mammals, including an interferon (IFN) inducible ~150 kD protein (ADAR1-p150) and a constitutively expressed ~110 kD protein (ADAR1-p110). The structural diversity of ADAR1 splicing isoforms may reflect their multiple functions. ADAR1 splicing isoforms were also found in fish. In our previous study, we have cloned and identified two different grass carp ADAR1 splicing isoforms, i.e. CiADAR1 and CiADAR1-like, both of them are IFN-inducible proteins. In this paper, we identified a novel CiADAR1 splicing isoform gene (named CiADAR1a). CiADAR1a gene contains 15 exons and 14 introns. Its full-length cDNA is comprised of a 5' UTR (359 bp), a 3' UTR (229 bp) and a 2952 bp ORF encoding a polypeptide of 983 amino acids with one Z-DNA binding domain, three dsRNA binding motifs and a highly conserved hydrolytic deamination domain. CiADAR1a was constitutively expressed in Ctenopharyngodon idella kidney (CIK) cells regardless of Poly I:C stimulation by Western blot assay. In normal condition, CiADAR1a was found to be present mainly in the nucleus. After treatment with Poly I:C, it gradually shifted to cytoplasm. To further investigate the mechanism of transcriptional regulation of CiADAR1a, we cloned and identified its promoter sequence. The transcriptional start site of CiADAR1a is mapped within the truncated exon 2. CiADAR1a promoter is 1303 bp in length containing 4 IRF-Es. In the present study, we constructed pcDNA3.1 eukaryotic expression vectors with IRF1 and IRF3 and co-transfected them with pGL3-CiADAR1a promoter into CIK cells. The results showed that neither the over expression of IRF1 or IRF3 nor Poly I:C stimulation significantly impacted CiADAR1a promoter activity in CIK cells. Together, according to the molecular and expression characteristics, subcellular localization and transcriptional regulatory mechanism, we deduced that CiADAR1a shared a high degree of homology with mammalian ADAR1-p110. PMID- 27185204 TI - Life-threatening hemorrhage after zygomatic bone surgery. About 2 posttraumatic cases. AB - INTRODUCTION: Management of zygomatic bone fractures is still debated. Method and delay for intervention has to be chosen considering respective issues of operative or conservative treatments, especially hemorrhagic complications. The maxillofacial surgeon must be able to determine life-threatening situations and to react appropriately. CASES REPORT: We report 2 cases of external carotid branches pseudoaneurysm leading to massive hemorrhage after early or delayed zygomatic fracture surgery. The first patient underwent open reduction of fracture by intraoral approach. An active bleeding occurred in the immediate postoperative time. In the second case, a zygomatic osteotomy was performed 1 year after fracture. Bleeding occurred 2 weeks after surgery. In both cases, angiography demonstrated a pseudoaneurysm developed from the external carotid branches. Embolisation led to rapid bleeding control. DISCUSSION: Severe hemorrhage resulting from maxillofacial trauma may be life-threatening. Once the "damage control" principles applied, selective embolisation of external carotid branches is an efficient alternative to surgery for the control of bleeding resulting from ruptured pseudoaneurysm. PMID- 27185205 TI - [Atraumatic bone expansion: Interest of piezo-surgery, conicals expanders and immediate implantation combination]. AB - The durability of dental implants depends on the presence of a 1mm coating bone sheath all around the fixture. Therefore, bone resorption represents a challenge for the practitioner. Bone expansion is a surgical technique that allows the management of horizontal bone atrophy. Cortical bone splitting allows for an enlargement of the residual crest by displacement of the vestibular bone flap. The immediate placement of implants secures the widening and allows for a 97% survival rate. However, bone expansion is hard to undertake in sites with high bone density. Furthermore, the use of traditional instruments increases patient's stress and the risk for an interruptive fracture during bone displacement. Non traumatic bone expansion is one solution to this problem. The combination of piezo-surgery and conical expanders allows for a secured displacement of the selected bone flap as well as an immediate implant placement, avoiding the risk of slipping, overheating, or fracture, all within an undeniable operative comfort. Non-traumatic bone expansion is a reliable, reproducible, conservative, and economical in time and cost procedure. We describe our atraumatic bone expension and immediate implant placement technique in high bone density sites and illustrate it by a clinical case. PMID- 27185206 TI - Calcium hydroxide as a processing base in alkali-aided pH-shift protein recovery process. AB - BACKGROUND: Protein may be recovered by using pH shifts to solubilize and precipitate protein. Typically, sodium hydroxide is used as the processing base; however, this has been shown to significantly increase sodium in the final recovered protein. RESULTS: Protein was extracted from black bullhead catfish (Ameiurus melas) using a pH-shift method. Protein was solubilized using either sodium hydroxide (NaOH) or calcium hydroxide (Ca(OH)2 ) and precipitated at pH 5.5 using hydrochloric acid (HCl). Protein solubility was greater when Ca(OH)2 was used compared to NaOH during this process. Using Ca(OH)2 as the processing base yielded the greatest lipid recovery (P < 0.05) at 77 g 100 g-1 , whereas the greatest (P < 0.05) protein recovery yield was recorded as 53 g 100 g-1 protein using NaOH. Protein solubilized with Ca(OH)2 had more (P < 0.05) calcium in the protein fraction, whereas using NaOH increased (P < 0.05) sodium content. CONCLUSION: Results of our study showed that protein solubility was increased and the recovered protein had significantly more calcium when Ca(OH)2 was used as the processing base. Results showed both NaOH and Ca(OH)2 to be an effective processing base for pH-shift protein recovery processes. (c) 2016 Society of Chemical Industry. PMID- 27185207 TI - Chronic myelomonocytic leukemia: 2016 update on diagnosis, risk stratification, and management. AB - Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder characterized by overlapping features of myelodysplastic syndromes and myeloproliferative neoplasms. Diagnosis is based on the presence of persistent (>3 months) peripheral blood monocytosis (>1 * 10(9) /L), along with bone marrow dysplasia. Clonal cytogenetic abnormalities occur in ~20-30% of patients, while >90% have gene mutations. Mutations involving TET2 (~60%), SRSF2 (~50%), ASXL1 (~40%), and RAS (~30%) are frequent; with only ASXL1 mutations negatively impacting overall survival. Two molecularly integrated, CMML-specific prognostic models include; the Groupe Francais des Myelodysplasies (GFM) and the Molecular Mayo Model (MMM). The GFM model segregates patients into 3 groups based on: age >65 years, WBC >15 * 10(9) /L, anemia, platelets <100 * 10(9) /L, and ASXL1 mutation status, with respective median survivals of 56 (low), 27.4 (intermediate), and 9.2 (high) months. The MMM is based on ASXL1 mutational status, absolute monocyte count >10 * 10(9) /L, hemoglobin <10 g/dL, platelets <100 * 109/L and circulating immature myeloid cells. This model stratifies patients into four groups; high (>=3 risk factors), intermediate-2 (2 risk factors), intermediate-1 (1 risk factor) and low (no risk factors), with median survivals of 16, 31, 59, and 97 months, respectively. Hypomethylating agents such as 5-azacitidine and decitabine are commonly used, with overall response rates of ~30-40% and complete remission rates of ~7-17%. Allogeneic stem cell transplant is the only potentially curative option, but is associated with significant morbidity and mortality. Individualized therapy, including epigenetic modifiers and small molecule inhibitors, are exciting prospects. Am. J. Hematol. 91:632 642, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27185208 TI - Homozygosity for a haplotype in the HBG2-OR51B4 region is exclusive to Arab Indian haplotype sickle cell anemia. PMID- 27185209 TI - Host glycosylation pathways and the unfolded protein response contribute to the infection by Francisella. AB - Protein glycosylation processes play a crucial role in most physiological functions, including cell signalling, cellular differentiation and adhesion. We previously demonstrated that rapid deglycosylation of membrane proteins was specifically triggered after infection of human macrophages by the bacterial pathogen Francisella tularensis. Using a glycan processing gene microarray, we found here that Francisella infection modulated expression of numerous glycosidase and glycosyltransferase genes. Furthermore, analysis of cell extracts from infected macrophages by Lectin and Western blotting revealed an important increase of N- and O-protein glycosylation. We chose to focus in the present work on one of the O-glycosylated proteins identified by mass spectrometry, the multifunctional endoplasmic reticulum chaperone BiP (HSPA5/GRP78). We demonstrate that BiP expression is modulated upon Francisella infection and is required to support its intracellular multiplication. Moreover, we show that Francisella differentially modulates the BiP-dependent activation of three key proteins of the unfolded protein response (UPR), IRE1, PERK and ATF6. The effects exerted on human cells by Francisella may thus constitute a novel excample of UPR manipulation contributing to intracellular bacterial adaptation. PMID- 27185210 TI - An Observational Study to Evaluate the Usability and Intent to Adopt an Artificial Intelligence-Powered Medication Reconciliation Tool. AB - BACKGROUND: Medication reconciliation (the process of creating an accurate list of all medications a patient is taking) is a widely practiced procedure to reduce medication errors. It is mandated by the Joint Commission and reimbursed by Medicare. Yet, in practice, medication reconciliation is often not effective owing to knowledge gaps in the team. A promising approach to improve medication reconciliation is to incorporate artificial intelligence (AI) decision support tools into the process to engage patients and bridge the knowledge gap. OBJECTIVE: The aim of this study was to improve the accuracy and efficiency of medication reconciliation by engaging the patient, the nurse, and the physician as a team via an iPad tool. With assistance from the AI agent, the patient will review his or her own medication list from the electronic medical record (EMR) and annotate changes, before reviewing together with the physician and making decisions on the shared iPad screen. METHODS: In this study, we developed iPad based software tools, with AI decision support, to engage patients to "self service" medication reconciliation and then share the annotated reconciled list with the physician. To evaluate the software tool's user interface and workflow, a small number of patients (10) in a primary care clinic were recruited, and they were observed through the whole process during a pilot study. The patients are surveyed for the tool's usability afterward. RESULTS: All patients were able to complete the medication reconciliation process correctly. Every patient found at least one error or other issues with their EMR medication lists. All of them reported that the tool was easy to use, and 8 of 10 patients reported that they will use the tool in the future. However, few patients interacted with the learning modules in the tool. The physician and nurses reported the tool to be easy-to-use, easy to integrate into existing workflow, and potentially time saving. CONCLUSIONS: We have developed a promising tool for a new approach to medication reconciliation. It has the potential to create more accurate medication lists faster, while better informing the patients about their medications and reducing burden on clinicians. PMID- 27185212 TI - Does enhancing personal care assistants' own oral health influence their attitudes and practices towards oral care for residents - a pilot study. AB - OBJECTIVES: To investigate whether, within a residential care facility, increasing personal care assistants' (PCAs) awareness of their own oral health status and self-care skills would alter existing attitudes and behavioural intentions related to the oral health care of residents. METHODS: PCAs (n = 15) in the dementia care unit of a residential care facility in Melbourne, Australia, were invited to participate in a small research project that appeared to test the effectiveness of a work-place oral health educational programme in enhancing their own oral health whilst masking the actual outcome of interest, namely its effect on PCAs oral healthcare attitudes and practices towards the residents. RESULTS: Post-intervention, the self-reported confidence of the PCAs to identify their personal risk for oral health problems, identifying common oral health conditions and determining the factors contributing to their personal oral health was increased significantly (P < 0.05). Post-intervention, the self-reported confidence of the PCAs to feeling confident to identify factors that could contribute to poor oral health of residents, identify resident's higher risk for poor oral health and feeling confident in identifying common oral health conditions in residents was also increased significantly (P < 0.05). CONCLUSION: The results of this pilot study show that the educational intervention to increase the personal care assistants' (PCAs) awareness of their own oral health status and self-care skills increased the confidence of the carers to identify oral health risks in the residents, as well as increasing their self-reported confidence in providing oral care to residents. PMID- 27185211 TI - Increased protein processing gene signature in HDACi-resistant cells predicts response to proteasome inhibitors. PMID- 27185214 TI - FTIR spectroscopy and scanning electron microscopic analysis of pretreated biosorbent to observe the effect on Cr (VI) remediation. AB - Various chemical and physical treatments have been applied to indigenously isolated cyanobacterial strain, Lyngbya putealis HH-15, to observe the effect on chromium removal capacity. Pretreatment with hydrochloric acid (99.1%) and nitric acid (98.5%) resulted in enhanced chromium removal as compared to untreated control biosorbent (98.1%). Pretreatment with acetic acid (97.9%), methanol (97.0%), calcium chloride (96.0%), hot water (95.2%), and sodium hydroxide (93.9%) did not improve the chromium removal capacity of biosorbent. Fourier transform infrared spectrometry (FTIR) and scanning electron microscopy (SEM) analysis identified changes in biomass functionality and availability after physical and chemical modification-the results of which were in agreement with metal removal studies. In conclusion, this acid-treated biosorbent represents a suitable candidate to replace conventional removal technologies for metal-bearing wastewaters. PMID- 27185213 TI - Reduction in squamous cell carcinomas in mouse skin by dietary zinc supplementation. AB - Inadequate dietary Zn consumption increases susceptibility to esophageal and other cancers in humans and model organisms. Since Zn supplementation can prevent cancers in rodent squamous cell carcinoma (SCC) models, we were interested in determining if it could have a preventive effect in a rodent skin cancer model, as a preclinical basis for considering a role for Zn in prevention of human nonmelanoma skin cancers, the most frequent cancers in humans. We used the 7,12 dimethyl benzanthracene carcinogen/phorbol myristate acetate tumor promoter treatment method to induce skin tumors in Zn-sufficient wild-type and Fhit (human or mouse protein) knockout mice. Fhit protein expression is lost in >50% of human cancers, including skin SCCs, and Fhit-deficient mice show increased sensitivity to carcinogen induction of tumors. We hypothesized that: (1) the skin cancer burdens would be reduced by Zn supplementation; (2) Fhit(-/-) (Fhit, murine fragile histidine triad gene) mice would show increased susceptibility to skin tumor induction versus wild-type mice. 30 weeks after initiating treatment, the tumor burden was increased ~2-fold in Fhit(-/-) versus wild-type mice (16.2 versus 7.6 tumors, P < 0.001); Zn supplementation significantly reduced tumor burdens in Fhit(-/-) mice (males and females combined, 16.2 unsupplemented versus 10.3 supplemented, P = 0.001). Most importantly, the SCC burden was reduced after Zn supplementation in both strains and genders of mice, most significantly in the wild-type males (P = 0.035). Although the mechanism(s) of action of Zn supplementation in skin tumor prevention is not known in detail, the Zn supplemented tumors showed evidence of reduced DNA damage and some cohorts showed reduced inflammation scores. The results suggest that mild Zn supplementation should be tested for prevention of skin cancer in high-risk human cohorts. PMID- 27185215 TI - Droplet-based magnetic bead immunoassay using microchannel-connected multiwell plates (MUCHAMPs) for the detection of amyloid beta oligomers. AB - Multiwell plates are regularly used in analytical research and clinical diagnosis but often require laborious washing steps and large sample or reagent volumes (typically, 100 MUL per well). To overcome such drawbacks in the conventional multiwell plate, we present a novel microchannel-connected multiwell plate (MUCHAMP) that can be used for automated disease biomarker detection in a small sample volume by performing droplet-based magnetic bead immunoassay inside the plate. In this MUCHAMP-based immunoassay platform, small volumes (30-50 MUL) of aqueous-phase working droplets are stably confined within each well by the simple microchannel structure (200-300 MUm in height and 0.5-1 mm in width), and magnetic beads are exclusively transported into an adjacent droplet through the oil-filled microchannels assisted by a magnet array aligned beneath and controlled by a XY-motorized stage. Using this MUCHAMP-based platform, we were able to perform parallel detection of synthetic amyloid beta (Abeta) oligomers as a model analyte for the early diagnosis of Alzheimer's disease (AD). This platform easily simplified the laborious and consumptive immunoassay procedure by achieving automated parallel immunoassay (32 assays per operation in 3-well connected 96-well plate) within 1 hour and at low sample consumption (less than 10 MUL per assay) with no cumbersome manual washing step. Moreover, it could detect synthetic Abeta oligomers even below 10 pg mL(-1) concentration with a calculated detection limit of ~3 pg mL(-1). Therefore, the MUCHAMP and droplet based magnetic bead immunoassay, with the combination of XY-motorized magnet array, would be a useful platform in the diagnosis of human disease, including AD, which requires low consumption of the patient's body fluid sample and automation of the entire immunoassay procedure for high processing capacity. PMID- 27185216 TI - Thiamine as a neuroprotective agent after cardiac arrest. AB - AIMS: Reduction of pyruvate dehydrogenase (PDH) activity in the brain is associated with neurological deficits in animals resuscitated from cardiac arrest. Thiamine is an essential co-factor of PDH. The objective of this study was to examine whether administration of thiamine improves outcomes after cardiac arrest in mice. Secondarily, we aimed to characterize the impact of cardiac arrest on PDH activity in mice and humans. METHODS: Animal study: Adult mice were subjected to cardiac arrest whereupon cardiopulmonary resuscitation was performed. Thiamine or vehicle was administered 2min before resuscitation and daily thereafter. Mortality, neurological outcome, and metabolic markers were evaluated. Human study: In a convenience sample of post-cardiac arrest patients, we measured serial PDH activity from peripheral blood mononuclear cells and compared them to healthy controls. RESULTS: Animal study: Mice treated with thiamine had increased 10-day survival (48% versus 17%, P<0.01) and improved neurological function when compared to vehicle-treated mice. In addition, thiamine markedly improved histological brain injury compared to vehicle. The beneficial effects of thiamine were accompanied by improved oxygen consumption in mitochondria, restored thiamine pyrophosphate levels, and increased PDH activity in the brain at 10 days. Human study: Post-cardiac arrest patients had lower PDH activity in mononuclear cells than did healthy volunteers (estimated difference: 5.8O.D./min/mg protein, P<0.001). CONCLUSIONS: The provision of thiamine after cardiac arrest improved neurological outcome and 10-day survival in mice. PDH activity was markedly depressed in post-cardiac arrest patients suggesting that this pathway may represent a therapeutic target. PMID- 27185217 TI - Therapeutic hypothermia and outcomes in paediatric out-of-hospital cardiac arrest: A nationwide observational study. AB - OBJECTIVES: This study aimed to analyse the association between mild therapeutic hypothermia (MTH) and outcomes in paediatric patients who survived out-of hospital cardiac arrest (OHCA) by using their initial electrocardiogram (ECG) rhythm, which is the key factor used to predict prognosis in paediatric OHCA. METHODS: This cross-sectional observational study utilised the registry of paediatric OHCA patients who survived to admission from 2008 to 2014 in the national OHCA database. MTH was defined as all cooling methods applied after the return of spontaneous circulation. Primary and secondary outcomes were survival to discharge and good neurologic recovery, respectively. Multivariable logistic regression analysis with an interaction term between MTH and the initial ECG at the scene was conducted to calculate adjusted odds ratios (AORs) and 95% confidence intervals (CIs) after adjusting for potential confounders. RESULTS: Among the 663 enrolled patients, the rates of survival to discharge and good neurological recovery in the MTH and non-MTH groups were similar, at 48.1% vs. 40.2% (P=0.17, AOR 1.05 [0.59-1.88]) and 22.2% vs. 8.7% (P=0.45, AOR 1.22 [0.59 2.51]). In the interaction model, the AORs of MTH in shockable rhythm vs. non shockable rhythm for survival to discharge (AOR 0.62 [0.15-2.52] vs. 1.17 [0.62 2.2]) and good neurological recovery (0.42 [0.12-1.45] vs. 2.22 [0.83-5.98]) were not significantly different. CONCLUSION: MTH and the effect of MTH across the initial ECG at the scene were not significantly associated with survival or good neurologic recovery in paediatric OHCA survivors. PMID- 27185218 TI - Risk factors and outcomes of in-hospital cardiac arrest following pediatric heart operations of varying complexity. AB - BACKGROUND: Multi center data regarding cardiac arrest in children undergoing heart operations of varying complexity are limited. METHODS: Children <18 years undergoing heart surgery (with or without cardiopulmonary bypass) in the Virtual Pediatric Systems (VPS, LLC) Database (2009-2014) were included. Multivariable mixed logistic regression models were adjusted for patient's characteristics, surgical risk category (STS-EACTS Categories 1, 2, and 3 classified as "low" complexity and Categories 4 and 5 classified as "high" complexity), and hospital characteristics. RESULTS: Overall, 26,909 patients (62 centers) were included. Of these, 2.7% had cardiac arrest after cardiac surgery with an associated mortality of 31%. The prevalence of cardiac arrest was lower among patients undergoing low complexity operations (low complexity vs. high complexity: 1.7% vs. 5.9%). Unadjusted outcomes after cardiac arrest were significantly better among patients undergoing low complexity operations (mortality: 21.6% vs. 39.1%, good neurological outcomes: 78.7% vs. 71.6%). In adjusted models, odds of cardiac arrest were significantly lower among patients undergoing low complexity operations (OR: 0.55, 95% CI: 0.46-0.66). Adjusted models, however, showed no difference in mortality or neurological outcomes after cardiac arrest regardless of surgical complexity. Further, our results suggest that incidence of cardiac arrest and mortality after cardiac arrest are a function of patient characteristics, surgical risk category, and hospital characteristics. Presence of around the clock in-house attending level pediatric intensivist coverage was associated with lower incidence of post-operative cardiac arrest, and presence of a dedicated cardiac ICU was associated with lower mortality after cardiac arrest. CONCLUSIONS: This study suggests that the patients undergoing high complexity operations are a higher risk group with increased prevalence of post-operative cardiac arrest. These data further suggest that patients undergoing high complexity operations can be rescued after cardiac arrest with a high survival rate. PMID- 27185219 TI - A Perovskite Electrocatalyst for Efficient Hydrogen Evolution Reaction. AB - Perovskite oxides are demonstrated for the first time as efficient electrocatalysts for the hydrogen evolution reaction (HER) in alkaline solutions. A-site praseodymium-doped Pr0.5 (Ba0.5 Sr0.5 )0.5 Co0.8 Fe0.2 O3- delta (Pr0.5BSCF) exhibits dramatically enhanced HER activity and stability compared to Ba0.5 Sr0.5 Co0.8 Fe0.2 O3- delta (BSCF), superior to many well-developed bulk/nanosized nonprecious electrocatalysts. The improved HER performance originates from the modified surface electronic structures and properties of Pr0.5BSCF induced by the Pr-doping. PMID- 27185221 TI - Positive-contrast cellular MRI of embryonic stem cells for tissue regeneration using a highly efficient T1 MRI contrast agent. AB - PURPOSE: To investigate the feasibility of high-sensitivity cellular MRI of embryonic stem (ES) cells using a novel cell permeable and cell retentive T1 contrast agent. MATERIALS AND METHODS: Mouse ES cells were labeled with a novel manganese porphyrin contrast agent, MnAMP, at 0.1 mM over 2 to 24 h and retained in contrast-free medium for up to 24 h postlabeling. MRI was performed on a 3 Tesla clinical scanner; T1 and T2 relaxation times were measured. Quantification of manganese content was performed using atomic absorption spectroscopy. Viability and proliferation assays were done for the longest labeling interval. Differentiation capacity was assessed using the hanging drop method to direct differentiation toward cardiomyocytes. RESULTS: MnAMP-labeled ES cells exhibited over a fourfold decrease in T1 compared with unlabeled cells, and maintained up to a threefold decrease 24 h postlabeling. Viability and proliferation were not affected. Most importantly, labeled ES cells differentiated into functional cardiomyocytes that exhibited normal contractility patterns. CONCLUSION: MnAMP based cellular MRI is a very high sensitivity T1 approach for cellular imaging. It has the potential for noninvasive in vivo monitoring of stem cell therapy in cardiac regeneration and other tissue engineering and regenerative medicine applications. J. Magn. Reson. Imaging 2016;44:1456-1463. PMID- 27185220 TI - Visible-light photoredox synthesis of unnatural chiral alpha-amino acids. AB - Unnatural chiral alpha-amino acids are widely used in fields of organic chemistry, biochemistry and medicinal chemistry, and their synthesis has attracted extensive attention. Although the asymmetric synthesis provides some efficient protocols, noble and elaborate catalysts, ligands and additives are usually required which leads to high cost. Distinctly, it is attractive to make unnatural chiral alpha-amino acids from readily available natural alpha-amino acids through keeping of the existing chiral alpha-carbon. However, it is a great challenge to construct them under mild conditions. In this paper, 83 unnatural chiral alpha-amino acids were prepared at room temperature under visible-light assistance. The protocol uses two readily available genetically coded proteinogenic amino acids, L-aspartic acid and glutamic acid derivatives as the chiral sources and radical precursors, olefins, alkynyl and alkenyl sulfones, and 2-isocyanobiphenyl as the radical acceptors, and various unnatural chiral alpha amino acids were prepared in good to excellent yields. The simple protocol, mild conditions, fast reactions, and high efficiency make the method an important strategy for synthesis of diverse unnatural chiral alpha-amino acids. PMID- 27185223 TI - Pediatric Reference Values and Z Score Equations for Left Ventricular Systolic Strain Measured by Two-Dimensional Speckle-Tracking Echocardiography. AB - BACKGROUND: In pediatric echocardiography, myocardial strain measurements are likely influenced by cardiac size and growth in healthy children. The application of this technique in clinical practice has been hampered by the lack of good normal reference values for the pediatric population. The aim of this study was to determine reference values and Z score equations for left ventricular systolic circumferential and longitudinal strain in a healthy pediatric population. METHODS: Two hundred thirty-three healthy subjects 1 to 18 years of age were prospectively recruited. Left ventricular systolic longitudinal and circumferential strain measurements were recorded using two-dimensional speckle tracking. Normalization for body size was performed using parametric nonlinear regression modeling. Several analyses were performed to detect potential residual associations with body size, residual heteroscedasticity, or departure from an adequate Z score distribution. RESULTS: There were weak but statistically significant nonlinear associations between body size and most strain values. Body surface area was superior to adjust for body size compared with age, height, and weight. Most strain values displayed a second-order polynomial relationship with body surface area. Z score equations were computed with adequate normal distributions and without residual associations in relation to BSA for most strain parameters. CONCLUSIONS: There was a weak but significant influence of body size on most left ventricular circumferential and longitudinal systolic strain parameters used in pediatric echocardiography. Z scores are presented for strain measurements normalized to body surface area and adjusted for heteroscedasticity. The use of these normalized values may reduce the risk for misclassification caused by normal variation in myocardial strain values during growth. PMID- 27185224 TI - A review of the neuroprotective role of vitamin D in traumatic brain injury with implications for supplementation post-concussion. AB - BACKGROUND: Nutritional interventions are promising treatment adjuncts in the management of concussion. Vitamin D (VDH) supplementation has demonstrated neuroprotective properties in multiple models of acquired brain injury. OBJECTIVE: Review the neuroprotective role of VDH supplementation following traumatic brain injury (TBI). METHODS: A Medline search was conducted to review manuscripts investigating the influence of VDH status or supplementation on TBI outcomes. RESULTS: The search identified 165 studies, of which five were included. Four manuscripts studied a rodent model of TBI, while one studied a clinical sample. Vitamin D monotherapy independently reduced inflammation and neuronal injury following TBI, with a more robust effect observed in combination with progesterone (PROG). One study demonstrated VDH deficiency exacerbates post TBI inflammatory response. One study in a clinical sample found combination therapy superior to PROG alone or placebo in improving outcomes after severe TBI. One study observed a more robust response to low-dose VDH compared to high-dose VDH when given in combination with PROG. CONCLUSION: A protective role for VDH and a vitamin D sufficient status was identified for numerous outcomes following TBI. However, VDH supplementation cannot be recommended at this time to improve outcomes following TBI. PMID- 27185225 TI - Design of Mixed-Metal Silver Decamolybdate Nanostructures for High Specific Energies at High Power Density. AB - Mixed-metal molybdates are interesting host materials for ion-insertion electrodes due to their versatile crystal chemistry, which confers a highway for the conduction of electrons as well as ions. Silver decamolybdate in triclinic crystal structure (T-Ag6 Mo10 O33 ) consists of layers of MoO6 octahedra separated by arrays of silver ions that are able to store a high amount of charges. PMID- 27185231 TI - Changes in volume during the four months' remodelling period of iliac crest grafts in reconstruction of the alveolar ridge. AB - Our aim was to assess the four months' resorption rates of onlay iliac crest grafts in atrophic jaws prospectively, and to identify factors that influence them. Twenty-four patients had reconstructions of the alveolar ridge with iliac crest onlay grafts at 30 sites on the mandibles and maxillas. The augmentation volumes were measured on cone-beam computed tomographic (CT) data-sets directly after augmentation (V1), and after four months' remodelling (V2). Statistical analysis allowed identification of potential influences from the recipient sites, volume of the graft, and the patients' smoking behaviour. The mean (range) initial onlay graft volume (V1) was 2.82 (0.66 to 6.41) ml. After four months, the mean measured onlay graft volume (V2) was 2.39 (0.47 to 6.21) ml. Mean iliac crest onlay graft volume resorption after four months of remodelling was 0.43 ( 0.15 - 1.78) ml (15%). We found no significant differences in the resorption rates of iliac crest onlay grafts between different recipient sites (maxilla and mandible) or in dependence on the volume of iliac crest grafts. Smokers tended to have a higher rate of resorption, but not significantly so (p=0.056). The results of this study indicate the most favourable resorption rates for iliac crest onlay grafts that we know have seen published to date. PMID- 27185230 TI - Leading article: Use of smartphones to pass on information about patients - what are the current issues? AB - Many doctors now use mobile devices such as smartphones to communicate with one another about their patients, and sometimes this is without the knowledge and approval of their employer. We know of little information about the use of texting and other web-based messaging services by doctors in hospitals, so we reviewed relevant published studies to assess the safety and usefulness of current methods of digital communication. PMID- 27185232 TI - Primary signet-ring cell adenocarcinoma of the head and neck: a case study and brief review. AB - We present a patient who had an aggressive primary signet-ring cell adenocarcinoma in the oral cavity that spread rapidly and led to his death. Most reports describe an indolent clinical course, but further reports are needed to better evaluate the particular clinical characteristics and course of this uncommon and biologically variable condition. PMID- 27185233 TI - Sialendoscopy and sialendoscopically-assisted operations in the treatment of lithiasis of the submandibular and parotid glands: our experience of 239 cases. AB - We present the results of treatment of sialolithiasis of the submandibular and parotid glands using sialendoscopy and sialendoscopy-assisted surgery. Between 2009-2013, 397 consecutive patients (mean (range) age 48 (18-76) years) were treated for obstructive diseases of the major salivary glands (sialolithiasis n=239, 175 submandibular and 64 parotid). In a total of 175 patients with 191 stones in the submandibular gland treated by endoscopic retrieval or surgical release, 149 patients (85%) were rendered free of stones (by sialendoscopy alone n=82, and sialendoscopy with operation n=67) Twenty patients (11%) had residual stones and 6 patients (4%) required excisionof the gland. Sixty-four patients had 71 stones removed from the parotid gland by endoscopic retrieval or surgical release and 43 (67%) were free of stones (by sialendoscopy alone n=25, and sialendoscopy with operation n=18). Twenty patients (31%) had residual stones and one (2%) required removal of the gland. In the group of patients whose stones were removed endoscopically, the effectiveness of sialendoscopy was 87% and 85%, respectively. We confirm that sialendoscopy and sialendoscopy-assisted removal is the current treatment of choice for stones in the submandibular and parotid glands. The indications for excision of the gland are becoming less common as first-line treatment, although it is still indispensable in some cases. PMID- 27185235 TI - Simple and effective method for observation of suspended parasite specimens using vaseline and paraffin mixture. AB - Parasitic specimens derived from protozoans and helminths have variable thickness. Therefore, microscopic observation of these specimens requires a preparation technique where the space between the coverslip and slide glass can be freely adjusted. However, standard suspension methods for parasites do not afford this flexibility due to the thickness of eggs and parasites. Mounting too large of a sample results in a floating coverslip, making observation difficult. In this article, we developed vaseline-paraffin solution (VPS) as a simple and effective mounting technique for observation of suspended parasite specimens. VPS placed between the coverslip and slide glass makes it possible to adjust the space between to accommodate specimens of variable thickness. For example, patterning of Toxocara egg surface protein layers can be observed using this improved method. Furthermore, VPS can be used as a sealing medium for long-term preservation. It is possible to keep suspended parasite specimens for more than two weeks. PMID- 27185234 TI - High-intensity cardiac infections of Phthinomita heinigerae n. sp. (Digenea: Aporocotylidae) in the orangelined cardinalfish, Taeniamia fucata (Cantor), off Heron Island on the Great Barrier Reef. AB - We report a new species of aporocotylid trematode (Platyhelminthes: Digenea) from the heart of the orangelined cardinalfish, Taeniamia fucata (Cantor), from off Heron Island on the southern Great Barrier Reef. We used an integrated approach, analysing host distribution, morphology, and genetic data from the internal transcribed spacer 2 of the ribosomal DNA, to circumscribe Phthinomita heinigerae n. sp. This is the first species of Phthinomita Nolan & Cribb, 2006 reported from the Apogonidae; existing species and known 'types' are recorded from species of the Labridae, Mullidae, and Siganidae. The new species is distinguished from its 11 congeners in having a body 2977-3539 long and 16.5-22.4 times longer than wide, an anterior testis 6.2-8.2 times longer than wide and 8.3-13.0 times longer than the posterior testis, a posterior testis whose width is 35-56% of the body width, and an ovary positioned 11-13% of the body length from the posterior end, and is entirely anterior to the posterior margin of the anterior testis. In addition, 2-34 base differences (0.4-7.0% sequence divergence over 485 base positions) were detected among the ITS2 sequence representing P. heinigerae n. sp. and the 14 representing other Phthinomita species/molecular types. Prevalence and intensity of infection with P. heinigerae n. sp. was relatively high within the heart tissue of T. fucata, with 19 of 20 fish examined from off Heron Island infected (95%) with 7-25 adult worms (arithmetic mean 16.6). Infections by these parasites accounted for an occupation of 7-30% of the total estimated heart volume. PMID- 27185236 TI - The Meaning of NMD: Translate or Perish. AB - Premature translation termination leads to a reduced mRNA level in all types of organisms. In eukaryotes, the phenomenon is known as nonsense-mediated mRNA decay (NMD). This is commonly regarded as the output of a specific surveillance and destruction mechanism that is activated by the presence of a premature translation termination codon (PTC) in an atypical sequence context. Despite two decades of research, it is still unclear how NMD discriminates between PTCs and normal stop codons. We suggest that cells do not possess any such mechanism and instead propose a new model in which this mRNA depletion is a consequence of the appearance of long tracts of mRNA that are unprotected by scanning ribosomes. PMID- 27185237 TI - Can Population Genetics Adapt to Rapid Evolution? AB - Population genetics largely rests on a 'standard model' in which random genetic drift is the dominant force, selective sweeps occur infrequently, and deleterious mutations are purged from the population by purifying selection. Studies of phenotypic evolution in nature reveal a very different picture, with strong selection and rapid heritable trait changes being common. The time-rate scaling of phenotypic evolution suggests that selection on phenotypes is often fluctuating in direction, allowing phenotypes to respond rapidly to environmental fluctuations while remaining within relatively constant bounds over longer periods. Whether such rapid phenotypic evolution undermines the standard model will depend on how many genomic loci typically contribute to strongly selected traits and how phenotypic evolution impacts the dynamics of genetic variation in a population. Population-level sequencing will allow us to dissect the genetic basis of phenotypic evolution and study the evolutionary dynamics of genetic variation through direct measurement of polymorphism trajectories over time. PMID- 27185238 TI - Dynamic Encounters of Genes and Transcripts with the Nuclear Pore. AB - Transcribed mRNA molecules must reach the cytoplasm to undergo translation. Technological developments in imaging have placed mRNAs under the spotlight, allowing the quantitative study of the spatial and temporal dynamics of the nucleocytoplasmic mRNA export process. Here, we discuss studies that have used such experimental approaches to demonstrate that gene tethering at the nuclear pore complex (NPC) regulates mRNA expression, and to characterize mRNA dynamics during transport in real time. The paths taken by mRNAs as they move from their sites of transcription and travel through the nucleoplasm, in between chromatin domains, and finally through the NPC, can now be observed in detail. PMID- 27185239 TI - Sensitive Electrochemiluminescence Immunosensor for Detection of N-Acetyl-beta-d glucosaminidase Based on a "Light-Switch" Molecule Combined with DNA Dendrimer. AB - Here, a novel "light-switch" molecule of Ru (II) complex ([Ru(dcbpy)2dppz](2+) DPEA) with self-enhanced electrochemiluminescence (ECL) property is proposed, which is almost nonemissive in aqueous solution but is brightly luminescent when it intercalates into DNA duplex. Owing to less energy loss and shorter electron transfer distance, the intramolecular ECL reaction between the luminescent [Ru(dcbpy)2dppz](2+) and coreactive tertiary amine group in N,N diisopropylethylenediamine (DPEA) makes the obtained "light-switch" molecule possess much higher light-switch efficiency compared with the traditional "light switch" molecule. For increasing the loading amount and further enhancing the luminous efficiency of the "light-switch" molecule, biotin labeled DNA dendrimer (the fourth generation, G4) is prepared from Y-shape DNA by a step-by-step assembly strategy, which provides abundant intercalated sites for [Ru(dcbpy)2dppz](2+)-DPEA. Meanwhile, the obtained nanocomposite (G4 [Ru(dcbpy)2dppz](2+)-DPEA) could well bind with streptavidin labeled detection antibody (SA-Ab2) due to the existence of abundant biotin. Through sandwiched immunoreaction, an ECL immunosensor was fabricated for sensitive determination of N-acetyl-beta-d-glucosaminidase (NAG), a typical biomarker for diabetic nephropathy (DN). The detemination linear range was 0.1 pg mL(-1) to 1 ng mL(-1), and the detection limit was 0.028 pg mL(-1). The developed strategy combining the ECL self-enhanced "light-switch" molecular and DNA nanotechnology offers an effective signal amplification mean and provides ample potential for further bioanalysis and clinical study. PMID- 27185240 TI - The effects in vitro of TNF-alpha and its antagonist 'etanercept' on ejaculated human sperm. AB - Tumour necrosis factor (TNF)-alpha is primarily involved in the regulation of cell proliferation and apoptosis; in addition it possesses pro-inflammatory properties. Anti-TNF-alpha strategies involve either administration of anti-TNF alpha antibody or soluble TNF receptor to mop up circulating TNF-alpha. Etanercept, a recombinant human TNF-alpha receptor, was found to be effective in the treatment of rheumatoid arthritis. The impact of TNF-alpha inhibitors on human fertility is of notable interest. This in vitro study investigated the effect of different concentrations of TNF-alpha and etanercept used alone or in combination on sperm viability, motility, mitochondrial function, percentage of apoptosis and chromatin integrity in swim-up selected human spermatozoa. A negative effect of TNF-alpha (300 and 500ng mL-1) and etanercept (from 800ug mL-1 to 2000ug mL-1) individually on sperm viability, motility, mitochondrial function, percentage of apoptotic spermatozoa and sperm DNA integrity was demonstrated. However, at concentrations of 100 and 200ug mL-1, etanercept can block, in a significant way, the toxic effects of TNF-alpha (500ng mL-1) on studied sperm characteristics. Our results confirm that TNF-alpha has a detrimental effect on sperm function and suggest, for the first time, that etanercept may counteract the in vitro toxic action of TNF-alpha. This data appears to be quite promising, although further studies, both in vivo and in vitro, are needed to understand the exact mechanism of action of TNF-alpha and TNF-alpha antagonists on sperm function. PMID- 27185241 TI - Enhancement of DNA double-strand break induction and cell killing by K-shell absorption of phosphorus in human cell lines. AB - PURPOSE: To investigate an enhancement of DNA double-strand break (DSB) induction and cell killing effect by K-shell ionization of phosphorus atoms and Auger electrons on human cell lines. MATERIALS AND METHODS: Induction of DSB, DNA damage responses, cell cycle distributions, and cell killing effects were investigated after exposures of the cells with monochromatic synchrotron radiation soft X-rays of 2153 and 2147 eV, which were the resonance peak and off peak, respectively, of the K-shell photoabsorption of phosphorus. RESULTS: Higher biological effects in the cells irradiated with soft X-rays at 2153 eV than at 2147 eV were observed in (i) the efficiency of 53BP1/gamma-H2AX co-localized foci formation per dose and residual number of foci, (ii) prolonged phosphorylation levels of DSB repair and/or cell cycle checkpoint related proteins and G2 arrest, (iii) the cell killing effects at the 10% survival level of normal human fibroblasts, HeLa cells, and human glioblastoma M059K cells (1.2-1.5 times higher) and that of human ataxia telangiectasia mutated (ATM)-defective cells and glioblastoma DNA-dependent protein kinase catalytic subunit (DNA-PKcs)-defective cells (1.2 times). CONCLUSION: The yield of DSB and partly less-reparable complex DNA damage induction in human cells was enhanced by K-shell photoabsorption of phosphorus and low-energy Auger electrons. PMID- 27185242 TI - Allergic disease and Staphylococcus aureus carriage in adolescents in the Arctic region of Norway. AB - BACKGROUND: Allergic diseases are common chronic diseases in children and adolescents, but limited epidemiological data are available during transition into adulthood. Nasal Staphylococcus aureus carriage has been linked to increased prevalence of allergic disease. The objective of this study was to define the prevalence of allergic diseases in adolescents above the Arctic Circle in Northern Norway and to study the associations of S. aureus carriage with allergic diseases. METHODS: A school-based cohort in late adolescence (18-19 years) was invited to participate in a cross-sectional study on lifestyle and health, and 868 attended (71.9%). Self-reported allergic disease and severity of eczema were assessed by Mechanisms of the Development of Allergy and Patient-Oriented Eczema Measure questionnaires. Participants were tested with spirometry and exhaled nitric oxide (FeNO) and swabbed for bacterial culture from nose and eczematous skin. RESULTS: We found asthma, eczema, allergic rhinitis (AR), and nasal S. aureus carriage among 11.9%, 10.4%, 26.0%, and 51.3% of the participants, respectively, and 10.2% had allergic multimorbidity. Lifetime prevalence for any allergic disease was 45.1%. Reduced lung function and increased FeNO were found in 11.6% and 22.1% in participants with asthma, respectively. Nasal S. aureus carriage was associated with eczema, severe asthma, and severe AR. FeNO > 25 ppb was associated with both asthma and nasal S. aureus carriage. CONCLUSION: Asthma, eczema, and AR are common among adolescents above the Arctic Circle in Norway. Allergic disease is associated with S. aureus carriage, but its role in the pathogenesis and severity is not established. PMID- 27185243 TI - Surgical repair of an aneurysm-like fistula connecting the left main coronary artery with the right atrium. AB - Coronary fistula is defined as an anomalous connection between a coronary artery and any of the four chambers of the heart or any of its great vessels. A coronary fistula connecting the left main coronary artery to the right atrium is the most uncommon. In the present study, we report the surgical management of a very uncommon case of an aneurysm-like fistula connecting the left main coronary artery to the right atrium in a 2-year-old boy. PMID- 27185244 TI - Prevalence, continuation, and identification of postpartum depressive symptomatology among refugee, asylum-seeking, non-refugee immigrant, and Canadian born women: results from a prospective cohort study. AB - This study assessed the prevalence, continuation, and identification of maternal depressive symptomatology over the first 16 weeks postpartum among refugee, asylum-seeking, non-refugee immigrant, and Canadian-born women. A sample of 1125 women (143 refugees, 369 asylum-seekers, 303 non-refugee immigrant, and 310 Canadian-born) completed the Edinburgh Postnatal Depression Scale (EPDS) at 1 and 16 weeks postpartum. The sensitivity, specificity, and predictive power of the 1 week EPDS to identify women with elevated EPDS scores at 16 weeks were determined. The total number of women with EPDS scores >9 for each group at 1 and 16 weeks, respectively, was 26.6 and 18.2 % for refugees; 25.2 and 24.1 % for asylum-seekers; 22.4 and 14.2 % for non-refugee immigrants, and 14.8 and 7.4 % for Canadian-born. Using the cut-off score of 9/10, the 1-week EPDS accurately classified 77.6 % refugee, 73.4 % asylum-seeking, 76.6 % non-refugee immigrant, and 85.5 % Canadian-born women at 16 weeks with or without postpartum depressive symptomatology. The 1-week EPDS was significantly correlated to the 16-week EPDS (r = 0.46, p < 0.01). All groups were significantly more likely to exhibit depressive symptomatology at 16 weeks if they had EPDS scores >9 at 1 week postpartum: refugees (OR = 6.9, 95 % CI = 2.8-17.3), asylum-seekers (OR = 4.0, 95 % CI = 2.4-6.7), non-refugee immigrants (OR = 3.8, 95 % CI = 2.0-7.6), and Canadian-born women (OR = 8.0, 95 % CI = 3.3-19.8). Our findings suggest that refugee, asylum-seeking, non-refugee immigrant, and Canadian-born women at risk of postpartum depression may be identified early in the postpartum period such that secondary preventive interventions may be implemented. PMID- 27185245 TI - Osthole Induces Cell Cycle Arrest and Inhibits Migration and Invasion via PTEN/Akt Pathways in Osteosarcoma. AB - BACKGROUND/AIMS: Osteosarcoma is the second highest cause of cancer-related death in children and adolescents. Majority of osteosarcoma patients (90%) show metastasis. Previous reports revealed that osthole showed antitumor activities via induction of apoptosis and inhibition of proliferation. However, the potential effects and detailed molecular mechanisms involved remained unclear. METHODS: Cell viability was analyzed by MTT assay in osteosarcoma cell lines MG 63 and SAOS-2. Cell cycle was detected by flow cytometry. The effects of migration and invasion were evaluated by wound healing assay and transwell assays. Moreover, the level of proteins expression was determined by Western blot. RESULTS: The cell viability of MG63 and SAOS-2 were markedly inhibited by osthole in a dose- and time-dependent manner. Cell cycle was arrested and the ability of migration and invasion was obviously reduced when cells were exposed to osthole. Moreover, enzymes involved in PTEN/Akt pathway were regulated such as PTEN and p-Akt proteins. Furthermore, osthole inhibited the tumor growth in vivo. CONCLUSION: Our study unraveled, for the first time, the ability of osthole to suppress osteosarcoma and elucidated the regulation of PTEN/Akt pathway as a signaling mechanism for the anti-tumor action of osthole. These findings indicate that osthole may represent a novel therapeutic strategy in the treatment of osteosarcoma. PMID- 27185247 TI - Influencing factors associated with the mode of birth among childbearing women in Hunan Province: a cross-sectional study in China. AB - BACKGROUND: An unnecessary Caesarean section (CS) can cause increased maternal and perinatal morbidity and other adverse short- and long-term outcomes. However, countries worldwide have witnessed an increasing trend toward the use of CS. Our objectives were to explore the influencing factors associated with the mode of birth among childbearing women in Hunan Province and to provide evidence and suggestions for the improvement and further understanding of vaginal birth (VB) in China. METHODS: A total of 977 childbearing women (375 pregnant women and 602 mothers of infants) were enrolled in this study using a two-stage cluster sampling method, and a self-administered questionnaire was used to collect data relating to the mode of birth. A t-test and chi (2)-test were used to analyse the differences between groups, and logistic regression analysis was used to explore the factors that influenced the mode of birth. RESULTS: The VB ratio was 46.2 %, while the CS ratio was 53.8 % in Hunan Province. Among women whose preference was VB, only 69.4 % gave birth by VB. Among women whose preference was CS, 98.1 % gave birth by CS. The top four reasons for preferring CS were a lack of confidence in VB (37.3 %), an abnormality in the prenatal examination (36.6 %), the notion that the baby would suffer fewer risks (34.8 %) and the fear of pain from VB (32.7 %). Age, prenatal examination, and doctors' suggestion were significantly associated with women's mode of birth preference, while place of household registration, husband's preference, prenatal examination and doctors' suggestion had a significant influence on women who changed their choice from VB to CS. CONCLUSIONS: The percentage of CS in Hunan was extremely high. Medical factors, such as abnormalities in prenatal examinations, and non-medical factors, such as a lack of confidence in VB, the fear of pain during VB, the desire to select the time of birth and healthy birth systems, should be seriously considered. Targeted health promotion interventions should be implemented to improve the performance of VB. PMID- 27185246 TI - Employment in French young adult survivors of childhood leukemia: an LEA study (for Leucemies de l'Enfant et de l'Adolescent-childhood and adolescent leukemia). AB - PURPOSE: Our principal aim was to assess the occupational outcomes of French survivors of childhood leukemia, compared to national population. The secondary objective was to identify determinants linked with employment stability after childhood leukemia. METHODS: All survivors aged 15 and over enrolled in the French LEA Cohort (Childhood and Adolescent Leukemia) were included. Occupational data were self-reported. The occupational distributions expected in the cohort for each age range were established based on the distribution in France as reference, and comparisons between observed and expected distributions were performed. Logistic regression model was used to explore determinants of stability of survivors' employment. RESULTS: The questionnaire was completed by 845 eligible survivors (response rate 87.8 %), with a mean age of 22.3 +/- 5.4 years and a mean follow-up duration of 14.3 +/- 6.3 years. Among the 361 survivors currently in the labor market, 36 (10.0 %) were seeking a job, which is significantly lower than expected (19.3 %) compared to French population. Conversely, among those currently employed, the number of survivors in unstable employment (43.9 %) was significantly higher than expected (33.5 %). Younger age and higher number of late effects were risk factors for unstable employment. CONCLUSIONS: While the employment rate of the young French adult population of childhood leukemia survivors seems rather positive, access to a steady job appears to be compromised for some survivors. IMPLICATIONS FOR CANCER SURVIVORS: A strategy to better identify particular subgroups of survivors at greatest risk for difficulties in their professional achievement will help ensure the development of specific intervention strategies and support procedures. PMID- 27185249 TI - Complexity: An interpretative phenomenological analysis of the experiences of mothers of deaf children with cochlear implants and autism. AB - The purpose of this study was to explore the experiences of parenting a child with a dual diagnosis of childhood deafness and autism spectrum disorder who underwent cochlear implantation. Experiences of these parents are rarely discussed within the literature. Interpretive Phenomenological Analysis was used to examine nine mothers of boys (4-9 years old) for understanding their parenting experiences. Three superordinate themes were identified: complexity, personal and family sacrifices and parent-professional partnerships. These themes provide a rich account of mothers' interpretations of their experiences, and reflect the numerous challenges they face. This study helps expand the literature on cochlear implantation for children with autism spectrum disorder, and discusses implications for clinical and educational practice. PMID- 27185248 TI - Transcriptome analysis of Sporisorium scitamineum reveals critical environmental signals for fungal sexual mating and filamentous growth. AB - BACKGROUND: Sporisorium scitamineum causes the sugarcane smut disease, one of the most serious constraints to global sugarcane production. S. scitamineum possesses a sexual mating system composed of two mating-type loci, a and b locus. We previously identified and deleted the b locus in S. scitamineum, and found that the resultant SsDeltaMAT-1b mutant was defective in mating and pathogenicity. RESULTS: To further understand the function of b-mating locus, we carried out transcriptome analysis by comparing the transcripts of the mutant strain SsDeltaMAT-1b, from which the SsbE1 and SsbW1 homeodomain transcription factors have previously been deleted, with those from the wild-type MAT-1 strain. Also the transcripts from SsDeltaMAT-1b X MAT-2 were compared with those from wild type MAT-1 X MAT-2 mating. A total of 209 genes were up-regulated (p < 0.05) in the SsDeltaMAT-1b mutant, compared to the wild-type MAT-1 strain, while 148 genes down-regulated (p < 0.05). In the mixture, 120 genes were up-regulated (p < 0.05) in SsDeltaMAT-1b X MAT-2, which failed to mate, compared to the wild-type MAT-1 X MAT-2 mating, and 271 genes down-regulated (p < 0.05). By comparing the up- and down-regulated genes in these two sets, it was found that 15 up-regulated and 37 down-regulated genes were common in non-mating haploid and mating mixture, which indeed could be genes regulated by b-locus. Furthermore, GO and KEGG enrichment analysis suggested that carbon metabolism pathway and stress response mediated by Hog1 MAPK signaling pathway were altered in the non-mating sets. CONCLUSIONS: Experimental validation results indicate that the bE/bW heterodimeric transcriptional factor, encoded by the b-locus, could regulate S. scitamineum sexual mating and/or filamentous growth via modulating glucose metabolism and Hog1-mediating oxidative response. PMID- 27185251 TI - Nutrition and Diet as It Relates to Health and Well-Being of Native Hawaiian Kupuna (Elders): A Systematic Literature Review. AB - PURPOSE: The key to improving the health and well-being of Native Hawaiians is to understand the historical events that have caused change to their diet and nutrition, and identify the connection between food, life, and the land. The purpose of this article is to (a) present a review of the literature addressing nutrition and diet as it relates to health and well-being of Native Hawaiian kupuna (elders) and (b) identify limitations and gaps to promote future research. DESIGN: This systematic literature review focused on 29 studies. FINDINGS: Native Hawaiians have the highest body mass index levels, highest daily energy (kilocalorie) intake, and lowest multivitamin use. They have the highest prevalence of diabetes and hypertension compared with Whites. Traditional Hawaiian diet programs and family support were beneficial to improving health and well-being. CONCLUSION: Future research of traditional Hawaiian diet programs and revitalization of the culture may lead to improving the health and well-being of Native Hawaiians. PMID- 27185250 TI - The Social Ecological Model and Physical Activity Interventions for Hispanic Women With Type 2 Diabetes: A Review. AB - Hispanic women are less physically active and have higher rates of type 2 diabetes (DM2) when compared with other population groups. This review uses the social ecological model as a framework to identify the individual and social environmental factors associated with successful physical activity (PA) interventions for Hispanic women with DM2. Research questions include (a) Which social ecological levels have been applied to PA interventions? (b) Which individual and social environmental intervention strategies are associated with successful PA outcomes? Database searches using CINAHL, PubMed, and Scopus for the years 2000 to 2015 identified 10 studies; with 6 using quasi-experimental study designs and 4 using randomized controlled designs. Inclusion criteria were Hispanic/Latina women with DM2, >=70% women, PA interventions, measures of PA, and quantitative designs. Future research should focus on a combination of intervention levels, and DM2 programs should place a greater emphasis on PA intervention strategies. PMID- 27185252 TI - Critiquing the response to the Ebola epidemic through a Primary Health Care Approach. AB - BACKGROUND: The 2014/2015 West Africa Ebola epidemic has caused the global public health community to engage in difficult self-reflection. First, it must consider the part it played in relation to an important public health question: why did this epidemic take hold and spread in this unprecedented manner? Second, it must use the lessons learnt to answer the subsequent question: what can be done now to prevent further such outbreaks in the future? These questions remain relevant, even as scientists announce that the Guinea Phase III efficacy vaccine trial shows that rVSV-EBOV (Merck, Sharp & Dohme) is highly efficacious in individuals. This is a major breakthrough in the fight against Ebola virus disease (EVD). It does not replace but may be a powerful adjunct to current strategies of EVD management and control. DISCUSSION: We contribute to the current self-reflection by presenting an analysis using a Primary Health Care (PHC) approach. This approach is appropriate as African countries in the region affected by EVD have recommitted themselves to PHC as a framework for organising health systems and the delivery of health services. The approach suggests that, in an epidemic made complex by weak pre-existing health systems, lack of trust in authorities and mobile populations, a broader approach is required to engage affected communities. In the medium-term health system development with attention to primary level services and community-based programmes to address the major disease burden of malaria, diarrhoeal disease, meningitis, tuberculosis and malnutrition is needed. This requires the development of local management and an investment in human resources for health. Crucially this has to be developed ahead of, and not in parallel with, future outbreaks. In the longer-term a commitment is required to address the underlying social determinants which make these countries so vulnerable, and limit their capacity to respond effectively to, epidemics such as EVD. CONCLUSION: The PHC approach offers an insightful critique of the global and regional factors which have compromised the response of health systems in Guinea, Liberia and Sierra Leone as well as suggesting what a strengthened EVD response might involve in the short, medium and long-term. PMID- 27185254 TI - Anatomical-Ultrasound Visor for Regional Anaesthesia. AB - INTRODUCTION: Regions considered optimal for performing peripheral nerve blocking have been well documented. However identify and perform regional anesthesia in those regions from ultrasound images remains a challenge. AIM: This study aims to develop a virtual environment for the simulation of ultrasound exploration of the neck nerves and both the upper and lower limbs for regional anesthesia. METHOD: Cross-sectional images were obtained from Magnetic Resonance Imaging for puncture regions involved in ultrasound-guided nerve block. RESULTS: A three-dimensional digital viewer was developed for the anatomical and ultrasound identification of key structures involved in peripheral nerve block in neck, upper and lower limbs. CONCLUSION: This study provides a virtual environment software used to simulate ultrasound exploration of nerve neck and upper and lower limbs for regional anesthesia. DISCUSSION: Potential implications of this tool for improving the ultrasound exploration for regional anesthesia and acquisition of anatomical knowledge are further discussed. PMID- 27185253 TI - Vagus Nerve Stimulation: Rapid versus Slow Cycling in a Laboratory Model. PMID- 27185255 TI - Distance Metric Based Oversampling Method for Bioinformatics and Performance Evaluation. AB - An imbalanced classification means that a dataset has an unequal class distribution among its population. For any given dataset, regardless of any balancing issue, the predictions made by most classification methods are highly accurate for the majority class but significantly less accurate for the minority class. To overcome this problem, this study took several imbalanced datasets from the famed UCI datasets and designed and implemented an efficient algorithm which couples Top-N Reverse k-Nearest Neighbor (TRkNN) with the Synthetic Minority Oversampling TEchnique (SMOTE). The proposed algorithm was investigated by applying it to classification methods such as logistic regression (LR), C4.5, Support Vector Machine (SVM), and Back Propagation Neural Network (BPNN). This research also adopted different distance metrics to classify the same UCI datasets. The empirical results illustrate that the Euclidean and Manhattan distances are not only more accurate, but also show greater computational efficiency when compared to the Chebyshev and Cosine distances. Therefore, the proposed algorithm based on TRkNN and SMOTE can be widely used to handle imbalanced datasets. Our recommendations on choosing suitable distance metrics can also serve as a reference for future studies. PMID- 27185257 TI - Immune response of turkey poults exposed at 1 day of age to either attenuated or wild Salmonella strains. AB - Salmonellosis is a foodborne zoonosis that is most often acquired by consuming poultry products such as eggs and poultry meat. Amongst other measures the vaccination of food-producing poultry is thought to contribute to a reduction in human salmonellosis. In the European Union (EU) in 2014 the licence of a commercially available Salmonella vaccine for chickens and ducks was extended to turkeys. In the present study, we examined the course of infection with a virulent Salmonella enterica ssp. enterica serovar Enteritidis (SE) strain, a virulent S. enterica ssp. enterica serovar Typhimurium (ST) strain, and the respective live vaccine containing attenuated strains of both serovars in turkey poults. Besides collecting microbiological data and detecting invading Salmonella in the caecal mucosa via immunohistochemistry, we also assessed immune reactions in terms of antibody production, influx of CD4-, CD8alpha- and CD28-positive cells into the caecal mucosa and the expression of four different immune-related proteins. We found that the attenuated strains were able to invade the caecum, but to a lower degree and for a shorter duration of time compared to virulent strains. Infections with virulent Salmonellae also caused an increase in CD4-, CD8alpha- and CD28-positive cells in the caecal mucosa and an increased transcription of iNOS, IL-8-like chemokines, and IFN-gamma. In poults treated with attenuated bacteria we could not detect any evidence of immune responses. In conclusion, the vaccine showed a lower degree of caecal invasion and induced weaker immune reactions compared to the virulent Salmonella strains in turkeys. The efficiency of the vaccine has to be verified in future studies. PMID- 27185258 TI - A proteomics-based identification of putative biomarkers for disease in bovine milk. AB - The objective of this study was to identify and characterize potential biomarkers for disease resistance in bovine milk that can be used to indicate dairy cows at risk to develop future health problems. We selected high- and low-resistant cows i.e. cows that were less or more prone to develop diseases according to farmers' experience and notifications in the disease registration data. The protein composition of milk serum samples of these high- and low-resistant cows were compared using NanoLC-MS/MS. In total 78 proteins were identified and quantified of which 13 were significantly more abundant in low-resistant cows than high resistant cows. Quantification of one of these proteins, lactoferrin (LF), by ELISA in a new and much larger set of full fat milk samples confirmed higher LF levels in low- versus high-resistant cows. These high- and low-resistant cows were selected based on comprehensive disease registration and milk recording data, and absence of disease for at least 4 weeks. Relating the experienced diseases to LF levels in milk showed that lameness was associated with higher LF levels in milk. Analysis of the prognostic value of LF showed that low-resistant cows with higher LF levels in milk had a higher risk of being culled within one year after testing than high-resistant cows. In conclusion, LF in milk are higher in low-resistant cows, are associated with lameness and may be a prognostic marker for risk of premature culling. PMID- 27185259 TI - Characterization of host responses induced by Toll-like receptor ligands in chicken cecal tonsil cells. AB - The innate responses of cecal tonsils against invading microorganisms are mediated by conserved pattern recognition receptors (PRRs) such as the Toll-like receptors (TLRs). TLRs expressed by mammalian and avian immune system cells have the capability to recognize pathogen-associated molecular patterns (PAMPs). Although, the role of TLR ligands in innate and adaptive responses in chickens has been characterized in spleen and bursa of Fabricius, considerably less is known about responses in cecal tonsils. The aim of the current study was to assess responses of mononuclear cells from cecal tonsils to treatment with the TLR2, TLR4 and TLR21 ligands, Pam3CSK4, lipopolysaccharide (LPS), and CpG oligodeoxynucleotide (ODN), respectively. All three ligands induced significant up-regulation of interferon (IFN)-gamma, interleukin (IL)-1beta, IL-6 and CxCLi2/IL-8, whereas no significant changes were observed in expression of IL-13 or the antimicrobial peptides, avian beta-defensin (AvBD) 1, AvBD2 and cathelicidin 3 (CATHL-3). In general, CpG ODN elicited the highest cytokine responses by cecal tonsil mononuclear cells, inducing significantly higher expression compared to LPS and Pam3CSK4, for IFNgamma, IL-1beta, IL-6 and CxCLi2 at various time points. These findings suggest the potential use of TLR21 ligands as mucosal vaccine adjuvants, especially in the context of pathogens of the intestinal tract. PMID- 27185256 TI - DNA hypermethylation of CD3(+) T cells from cord blood of infants exposed to intrauterine growth restriction. AB - AIMS/HYPOTHESIS: Intrauterine growth restriction (IUGR) is associated with increased susceptibility to obesity, metabolic syndrome and type 2 diabetes. Although the mechanisms underlying the developmental origins of metabolic disease are poorly understood, evidence suggests that epigenomic alterations play a critical role. We sought to identify changes in DNA methylation patterns that are associated with IUGR in CD3(+) T cells purified from umbilical cord blood obtained from male newborns who were appropriate for gestational age (AGA) or who had been exposed to IUGR. METHODS: CD3(+) T cells were isolated from cord blood obtained from IUGR and AGA infants. The genome-wide methylation profile in eight AGA and seven IUGR samples was determined using the HELP tagging assay. Validation analysis using targeted bisulfite sequencing and bisulfite massARRAY was performed on the original cohort as well as biological replicates consisting of two AGA and four IUGR infants. The Segway algorithm was used to identify methylation changes within regulatory regions of the genome. RESULTS: A global shift towards hypermethylation in IUGR was seen compared with AGA (89.8% of 4,425 differentially methylated loci), targeted to regulatory regions of the genome, specifically promoters and enhancers. Pathway analysis identified dysregulation of pathways involved in metabolic disease (type 2 diabetes mellitus, insulin signalling, mitogen-activated protein kinase signalling) and T cell development, regulation and activation (T cell receptor signalling), as well as transcription factors (TCF3, LEF1 and NFATC) that regulate T cells. Furthermore, bump-hunting analysis revealed differentially methylated regions in PRDM16 and HLA-DPB1, genes important for adipose tissue differentiation, stem cell maintenance and function and T cell activation. CONCLUSIONS/INTERPRETATION: Our findings suggest that the alterations in methylation patterns observed in IUGR CD3(+) T cells may have functional consequences in targeted genes, regulatory regions and transcription factors. These may serve as biomarkers to identify those at 'high risk' for diminished attainment of full health potential who can benefit from early interventions. ACCESS TO RESEARCH MATERIALS: HELP tagging data: Gene Expression Omnibus database (GSE77268), scheduled to be released on 25 January 2019. PMID- 27185261 TI - Comparison of the immune competence of Turopolje, German Landrace * Turopolje, and German Landrace * Pietrain pigs after PRRSV vaccination. AB - The competences of the immune systems of the ancient pig breed Turopolje (T*T), German Landrace * Turopolje (L*T) and 'modern' pig breed German Landrace * Pietrain (L*P) were compared in this study. All pigs were immunized with a modified live vaccine against 'Porcine Reproductive and Respiratory Syndrome' (PRRS) virus (Ingelvac PRRS MLV((r))) to simulate an infection. Antibody production against PRRS MLV was evaluated in serum. Elimination of the viral infectious fragments during the experimental period was monitored in serum, leukocytes and tonsils by RT-qPCR. Furthermore relevant immune marker genes were quantified either on gene expression level using RT-qPCR [toll like receptor (TLR) 7, TLR8, TRAF6, CD163, SIGLEC1, CD4, CD8, CD14, CD19, tumor necrosis factor alpha (TNFalpha), interleukin (IL) 1, IL2, IL6, IL12], and on protein level using ELISA [interleukin (IL)-1, IL-2, IL-6, and IL-12]. The three breeds showed individual inactivation efficiencies as a reaction to the PRRS MLV vaccination. T*T eliminated the virus in serum within 16 days, followed by L*T (28 days) and L*P (36 days). The antibody titers against PRRS MLV of L*T and L*P were significantly higher compared to T*T (p<0.05). The gene expression data and protein analysis of interleukins revealed that T*T reacted with a type 1 immune response. In contrast, the two other breeds (L*T and L*P) showed a type 2 immune response, which resulted in the higher synthesis of B-cells and an increased concentration of specific anti-PRRS MLV antibodies. PMID- 27185260 TI - Evidence for the existence of regulatory and effector B cell populations in Peyer's patches of sheep. AB - IL-10 secreting CD21(+) B cells exist in sheep Peyer's patches (PP). It's not known however, whether all PP B cells are regulatory or whether an effector population also exists in this tissue. To further characterize the subpopulations of B cells in PP's, highly purified B cells were negatively sorted from jejunal PP and fractionated according to co-expression of CD72(+)CD21(+)or CD72(+)CD21(-) molecules and then stimulated with the TLR9-agonist, CpG ODN. IL-10, IL-12, IFN gamma, and IgM production were then assayed. We observed that only highly purified CD72(+)CD21(+) B cells spontaneously secreted high levels of IL-10, but they did not produce any IL-12, IFN-gamma or IgM suggesting that this cell population contains regulatory B cells. In contrast, CD72(+)CD21(-) B cells did not secrete IL-10, but secreted IL-12, IFN-gamma, and IgM, suggesting they include effector cells. In addition, B cells expressing surface IgA, IgM and IgG1 all secreted similar levels of IL-10. We further confirmed that only B cells produce IL-10, while other cells in the PP including DCs and T cells do not. Our investigations may provide evidence for the existence of two sub-populations in sheep PP; IL-10 secreting regulatory (CD72(+)CD21(+)) cells, and IL-12/IFN gamma/IgM-secreting effector (CD72(+)CD21(-)) cells. PMID- 27185262 TI - Efficacy of an inactivated genotype 2b porcine epidemic diarrhea virus vaccine in neonatal piglets. AB - Massive outbreaks of porcine epidemic diarrhea virus (PEDV) recurred in South Korea in 2013-2014 and affected approximately 40% of the swine breeding herds across the country, incurring a tremendous financial impact on producers and consumers. Despite the nationwide use of commercially available attenuated and inactivated vaccines in South Korea, PEDV has continued to plague the domestic pork industry, raising concerns regarding their protective efficacies and the need for new vaccine development. In a previous study, we isolated and serially cultivated a Korean PEDV epidemic strain, KOR/KNU-141112/2014, in Vero cells. With the availability of a cell culture-propagated PEDV strain, we are able to explore vaccination and challenge studies on pigs. Therefore, the aim of the present study was to produce an inactivated PEDV vaccine using the KNU-141112 strain and evaluate its effectiveness in neonatal piglets. Pregnant sows were immunized intramuscularly with the inactivated adjuvanted monovalent vaccine at six and three weeks prior to farrowing. Six-day-old piglets born to vaccinated or unvaccinated sows were challenged with the homogeneous KNU-141112 virus. The administration of the inactivated vaccine to sows greatly increased the survival rate of piglets challenged with the virulent strain, from 0% to approximately 92% (22/24), and significantly reduced diarrhea severity including viral shedding in feces. In addition, litters from unvaccinated sows continued to lose body weight throughout the experiment, whereas litters from vaccinated sows started recovering their daily weight gain at 7 days after the challenge. Furthermore, strong neutralizing antibody responses to PEDV were verified in immunized sows and their offspring, but were absent in the unvaccinated controls. Altogether, our data demonstrated that durable lactogenic immunity was present in dams administrated with the inactivated vaccine and subsequently conferred critical passive immune protection to their own litters against virulent PEDV infection. PMID- 27185263 TI - Passive immunisation, an old idea revisited: Basic principles and application to modern animal production systems. AB - Immunisation by administration of antibodies (immunoglobulins) has been known for more than one hundred years as a very efficient means of obtaining immediate, short-lived protection against infection and/or against the disease-causing effects of toxins from microbial pathogens and from other sources. Thus, due to its rapid action, passive immunisation is often used to treat disease caused by infection and/or toxin exposure. However immunoglobulins may also be administered prior to exposure to infection and/or toxin, although they will not provide long lasting protection as is seen with active immunisation (vaccination) in which an immunological memory is established by controlled exposure of the host to the pathogen in question. With multi-factorial infectious diseases in production animals, especially those that have proven hard to control by vaccination, the potential of passive immunisation remains big. This review highlights a number of examples on the use of passive immunisation for the control of infectious disease in the modern production of a range of animals, including pigs, cattle, sheep, goat, poultry and fish. Special emphasis is given on the enablement of passive immunisation strategies in these production systems through low cost and ease of use as well as on the sources, composition and purity of immunoglobulin preparations used and their benefits as compared to current measures, including vaccination (also comprising maternal vaccination), antibiotics and feed additives such as spray-dried plasma. It is concluded that provided highly efficient, relatively low-price immunoglobulin products are available, passive immunisation has a clear role in the modern animal production sector as a means of controlling infectious diseases, importantly with a very low risk of causing development of bacterial resistance, thus constituting a real and widely applicable alternative to antibiotics. PMID- 27185265 TI - MicroRNA-93 promotes the malignant phenotypes of human glioma cells and induces their chemoresistance to temozolomide. AB - MicroRNAs (miRNAs), a class of small non-coding RNAs, can induce mRNA degradation or repress translation by binding to the 3'-untranslated region (UTR) of its target mRNA. Recently, some specific miRNAs, e.g. miR-93, have been found to be involved in pathological processes by targeting some oncogenes or tumor suppressors in glioma. However, the regulatory mechanism of miR-93 in the biological behaviors and chemoresistance of glioma cells remains unclear. In the present study, in situ hybridization and real-time RT-PCR data indicated that miR 93 was significantly upregulated in glioma patients (n=43) compared with normal brain tissues (n=8). Moreover, the upregulated miR-93 level was significantly associated with the advanced malignancy. We also found that upregulation of miR 93 promoted the proliferation, migration and invasion of glioma cells, and that miR-93 was involved in the regulation of cell cycle progression by mediating the protein levels of P21, P27, P53 and Cyclin D1. P21 was further identified as a direct target of miR-93. Knockdown of P21 attenuated the suppressive effects of miR-93 inhibition on cell cycle progression and colony formation. In addition, inhibition of miR-93 enhanced the chemosensitization of glioma cells to temozolomide (TMZ). Based on these above data, our study demonstrates that miR 93, upregulated in glioma, promotes the proliferation, cell cycle progression, migration and invasion of human glioma cells and suppresses their chemosensitivity to TMZ. Therefore, miR-93 may become a promising diagnostic marker and therapeutic target for glioma. PMID- 27185264 TI - Correlative near-infrared light and cathodoluminescence microscopy using Y2O3:Ln, Yb (Ln = Tm, Er) nanophosphors for multiscale, multicolour bioimaging. AB - This paper presents a new correlative bioimaging technique using Y2O3:Tm, Yb and Y2O3:Er, Yb nanophosphors (NPs) as imaging probes that emit luminescence excited by both near-infrared (NIR) light and an electron beam. Under 980 nm NIR light irradiation, the Y2O3:Tm, Yb and Y2O3:Er, Yb NPs emitted NIR luminescence (NIRL) around 810 nm and 1530 nm, respectively, and cathodoluminescence at 455 nm and 660 nm under excitation of accelerated electrons, respectively. Multimodalities of the NPs were confirmed in correlative NIRL/CL imaging and their locations were visualized at the same observation area in both NIRL and CL images. Using CL microscopy, the NPs were visualized at the single-particle level and with multicolour. Multiscale NIRL/CL bioimaging was demonstrated through in vivo and in vitro NIRL deep-tissue observations, cellular NIRL imaging, and high-spatial resolution CL imaging of the NPs inside cells. The location of a cell sheet transplanted onto the back muscle fascia of a hairy rat was visualized through NIRL imaging of the Y2O3:Er, Yb NPs. Accurate positions of cells through the thickness (1.5 mm) of a tissue phantom were detected by NIRL from the Y2O3:Tm, Yb NPs. Further, locations of the two types of NPs inside cells were observed using CL microscopy. PMID- 27185266 TI - Body-enlarging effect of royal jelly in a non-holometabolous insect species, Gryllus bimaculatus. AB - Honeybee royal jelly is reported to have body-enlarging effects in holometabolous insects such as the honeybee, fly and silkmoth, but its effect in non holometabolous insect species has not yet been examined. The present study confirmed the body-enlarging effect in silkmoths fed an artificial diet instead of mulberry leaves used in the previous literature. Administration of honeybee royal jelly to silkmoth from early larval stage increased the size of female pupae and adult moths, but not larvae (at the late larval stage) or male pupae. We further examined the body-enlarging effect of royal jelly in a non holometabolous species, the two-spotted cricket Gryllus bimaculatus, which belongs to the evolutionarily primitive group Polyneoptera. Administration of royal jelly to G. bimaculatus from its early nymph stage enlarged both males and females at the mid-nymph and adult stages. In the cricket, the body parts were uniformly enlarged in both males and females; whereas the enlarged female silkmoths had swollen abdomens. Administration of royal jelly increased the number, but not the size, of eggs loaded in the abdomen of silkmoth females. In addition, fat body cells were enlarged by royal jelly in the silkmoth, but not in the cricket. These findings suggest that the body-enlarging effect of royal jelly is common in non-holometabolous species, G. bimaculatus, but it acts in a different manner than in holometabolous species. PMID- 27185267 TI - Effects of TiO2 nanoparticles on nutrition metabolism in silkworm fat body. AB - Silkworm (Bombyx mori) is an important economic insect with a fat body that plays a crucial role in the storage and transfer of nutrients. It is also known that TiO2 nanoparticles (NPs) can improve feed efficiency and promote silk protein synthesis in the silkworm. In this study, we profiled gene expression in the silkworm fat body after TiO2 NP treatment, validated the major RNA-seq findings, and determined the contents of trehalose and triglyceride, the activity of lipase, and the amount of total proteins. RNA-seq analysis revealed that TiO2 NP treatment caused significant expression changes in 341 genes (P<=0.01), 138 of which were upregulated while the other 203 were downregulated. The expression levels of two target genes in the insulin signaling pathway and two protein metabolism-related target genes, three lipid metabolism-associated target genes, two carbohydrate metabolism related target genes and expression levels of seven heat shock protein genes were increased, and that of threonine dehydratase gene and fatty acid transport protein gene were decreased. The RNA-seq results of 16 genes were validated by quantitative real-time PCR. The lipase activity, content of trehalose, and amount of total proteins were elevated by 3.86-fold, 1.34-fold, and 1.21-fold, respectively, and the content of triglyceride was decreased by 0.94-fold after TiO2 NP treatment. These results indicated that TiO2 NPs activated the insulin signaling pathway, promoted the metabolism of protein, fat, and carbohydrate, and improved nutrition metabolism. Our study provides new support for the understanding of the beneficial effect of TiO2 NPs on silkworm nutrient metabolism. PMID- 27185268 TI - Downregulation of leptin inhibits growth and induces apoptosis of lung cancer cells via the Notch and JAK/STAT3 signaling pathways. AB - Previous studies have documented that leptin is involved in the pathogenesis of many human cancer types by regulation of numerous signal transduction pathways. The aim of this study was to investigate the biological roles of leptin and the mechanisms attributed to its action in non-small cell lung cancer (NSCLC) cell lines. The expression of leptin was measured by quantitative real-time PCR and western blot in seven NSCLC cell lines. Proliferation and apoptosis of NSCLC cells in response to leptin knockdown were determined by MTT assay and flow cytometry, respectively. The effect of leptin knockdown on the Notch and JAK/STAT3 signaling pathways was further examined by western blot. Leptin expression was significantly increased in NSCLC cell lines compared with normal human bronchial epithelial cell HBE. Leptin knockdown inhibited cell proliferation and induced apoptosis in NSCLC cell lines through inactivation of the Notch and JAK/STAT3 signaling pathways. Furthermore, gene silencing of Notch signaling with Notch-1 siRNA or inhibition of JAK/STAT3 signaling by JSI-124, an inhibitor of STAT3, resulted in proliferation inhibition and apoptosis induction in NSCLC A549 cells. Our findings suggested that leptin knockdown could become a new approach for the prevention of lung cancer progression, which is likely to be mediated at least partially by inactivation of the Notch and JAK/STAT3 signaling pathways. PMID- 27185269 TI - Role of carriers in the transmission of pneumonia in bighorn sheep (Ovis canadensis). AB - In the absence of livestock contact, recurring lamb mortality in bighorn sheep (Ovis canadensis) populations previously exposed to pneumonia indicates the likely presence of carriers of pneumonia-causing pathogens, and possibly inadequate maternally derived immunity. To investigate this problem we commingled naive, pregnant ewes (n=3) with previously exposed rams (n=2). Post-commingling, all ewes and lambs born to them acquired pneumonia-causing pathogens (leukotoxin producing Pasteurellaceae and Mycoplasma ovipneumoniae), with subsequent lamb mortality between 4-9 weeks of age. Infected ewes became carriers for two subsequent years and lambs born to them succumbed to pneumonia. In another experiment, we attempted to suppress the carriage of leukotoxin-producing Pasteurellaceae by administering an antibiotic to carrier ewes, and evaluated lamb survival. Lambs born to both treatment and control ewes (n=4 each) acquired pneumonia and died. Antibody titers against leukotoxin-producing Pasteurellaceae in all eight ewes were 'protective' (>1:800 and no apparent respiratory disease); however their lambs were either born with comparatively low titers, or with high (but non-protective) titers that declined rapidly within 2-8 weeks of age, rendering them susceptible to fatal disease. Thus, exposure to pneumonia-causing pathogens from carrier ewes, and inadequate titers of maternally derived protective antibodies, are likely to render bighorn lambs susceptible to fatal pneumonia. PMID- 27185273 TI - PyFREC: Software for Forster electronic coupling evaluation in molecular fragments. AB - Electronic couplings are crucial for understanding exciton dynamics and associated energy transfer in artificial and natural chromophores. The proposed PyFREC (Python FRagment Electronic Coupling) software enables evaluation of electronic couplings based on the Forster model. PyFREC features the decomposition of electronic couplings, obtained through quantum chemical calculations, into the orientation and dipole strength components. Furthermore, the variation method to evaluate energies of coupled electronic excited states and delocalization of electronic excitations is implemented in the software. PyFREC has been tested on the S22 benchmark dataset of non-covalent complexes and water clusters. (c) 2016 Wiley Periodicals, Inc. PMID- 27185270 TI - Patients' expectations of the role of the community pharmacist: Development and testing of a conceptual model. AB - BACKGROUND: The roles of community pharmacists are evolving to include provision of expanded professional pharmacy services, thus leading to an increased interest in pharmacist-patient interactions. Role theory can be used to explain the interaction between this pair of individuals, by focusing on the roles performed by each one. OBJECTIVE: To develop and test a model that relates patients' image of the pharmacist to their expectations of pharmacist's role, and how this then influences patients' reactions toward the pharmacist's role. METHODS: A qualitative study was undertaken, and a questionnaire was created for the development of the model, based on role theory. The content, dimensions, validity and reliability of the questionnaire were pre-tested qualitatively and in a pilot mail survey. The reliability and validity of the proposed model were tested using confirmatory factor analysis (CFA). Structural equation modelling (SEM) was used to explain relationships between dimensions of the final model. RESULTS: A final model was developed. CFA concluded that the model was valid and reliable (Goodness of Fit indices: chi2(109) = 227.662, P = 0.000, RMSEA = 0.05, SRMR = 0.05, GFI = 1.00, NNFI = 0.90, CFI = 0.92). SEM indicated that "perceived pharmacist image" was associated positively and significantly with both "professional expectations" (the standardized path coefficient of (H) = 0.719, P < 0.05), as well as "courtesy expectations" (the standardized path coefficient of (H) = 0.582, P < 0.05). At the same time, "professional expectations" were associated positively and significantly with "positive reactions" (the standardized path coefficient of (H) = 0.358, P < 0.05), but negatively with "Negative reactions" (the standardized path coefficient of (H) = -0.427, P < 0.05). "Courtesy expectations" were associated positively and significantly with "positive reactions" (the standardized path coefficient of (H) = 0.081, P < 0.05), as well as "negative reactions" (the standardized path coefficient of (H) = 0.450, P < 0.05). CONCLUSIONS: A valid and reliable model of patients' image of the pharmacist related to their expectations and reactions to the pharmacist's role was developed and tested. When the perceived image of the pharmacist is enhanced, patients' expectations of the pharmacist are heightened; in turn, these expectations were associated with reactions of patients. PMID- 27185271 TI - Phrenic motor neuron TrkB expression is necessary for acute intermittent hypoxia induced phrenic long-term facilitation. AB - Phrenic long-term facilitation (pLTF) is a form of hypoxia-induced spinal respiratory motor plasticity that requires new synthesis of brain derived neurotrophic factor (BDNF) and activation of its high-affinity receptor, tropomyosin receptor kinase B (TrkB). Since the cellular location of relevant TrkB receptors is not known, we utilized intrapleural siRNA injections to selectively knock down TrkB receptor protein within phrenic motor neurons. TrkB receptors within phrenic motor neurons are necessary for BDNF-dependent acute intermittent hypoxia-induced pLTF, demonstrating that phrenic motor neurons are a critical site of respiratory motor plasticity. PMID- 27185272 TI - Bile acids induce activation of alveolar epithelial cells and lung fibroblasts through farnesoid X receptor-dependent and independent pathways. AB - BACKGROUND AND OBJECTIVE: The roles of bile acid microaspiration and bile acid activated farnesoid X receptor (FXR) in the pathogenesis of idiopathic pulmonary fibrosis (IPF) remain unclear. We hypothesized that bile acids activate alveolar epithelial cells (AECs) and lung fibroblasts, which may be regulated by FXR activation. METHODS: Human AECs and normal or IPF-derived lung fibroblast cells were incubated with the three major bile acids: lithocholic acid (LCA), deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA). The AECs injury indices, epithelial-mesenchymal transition (EMT) and lung fibroblast activation were evaluated. FXR expression in IPF lungs and the roles of FXR and FXR-independent pathways in bile acid-induced profibrotic effects were also investigated. RESULTS: LCA, DCA and CDCA reduced cell viability and increased intracellular reactive oxygen species (ROS) production in A549 cells. They all induced EMT, as shown by enhanced alpha-SMA and vimentin and decreased E-cadherin levels. LCA directly induced differentiation of lung fibroblasts to myofibroblasts. All three bile acids promoted cellular migration but not proliferation of lung fibroblasts. FXR expression was upregulated in IPF lungs, and inhibition of FXR restrained the bile acid-induced EMT and lung fibroblast activation. Differentiation and proliferation were enhanced in lung fibroblasts exposed to conditioned medium from bile acid-stimulated A549 cells, which contained increased levels of profibrotic factors. TGF-beta/Smad3 signaling was also involved in the bile acid induced EMT and lung fibroblast differentiation. CONCLUSION: Bile acid microaspiration may promote the development of pulmonary fibrosis by inducing activation of AECs and lung fibroblasts via FXR-dependent and independent pathways. PMID- 27185274 TI - Epidemiology and detection of acinetobacter using conventional culture and in house developed PCR based methods. AB - Active surveillance cultures for multidrug-resistant (MDR) gram-negative bacteria is one strategy to control outbreaks. The objectives of the study are to evaluate the prevalence of Acinetobacter colonization and to compare conventional culture and in-house developed PCR based method. Swabs were collected from patients transferred from another organization or were admitted to the intensive care units. Swabs were cultured by conventional method and were tested using in-house LightCycler(r) 2.0 real-time PCR method. Of 449 tested samples, the majority came from cardiac step down unit (188, 42%), male medical floor (80; 18%), and coronary care unit (66; 13.4%). Of the total specimens, 14 (3%) were positive by PCR and 12 (2.6%) were positive by routine cultures. The positivity rates among wounds, respiratory, perineal, and nasal samples were 3.2%, 9.7%, 4.6% and 0.8% respectively. Two positive samples by PCR were negative by routine culture. The overall concordance rate was 99.5% and the positive concordance rate was 85.7%. The current study revealed a low prevalence of MDR Acinetobacter among the studied population. The LightCycler(r) 2.0 PCR produced comparable positive results to routine cultures. PMID- 27185275 TI - Clinical and microbiological features of resistant gram-negative bloodstream infections in children. AB - BACKGROUND: Bloodstream infections (BSIs) caused by Gram-negative (GN) bacteria cause significant morbidity and mortality. There is a worldwide increase in the reported incidence of resistant microorganisms; therefore, surveillance programs are important to define resistance patterns of GN microorganisms causing BSIs. The objective of this study was to describe the clinical and microbiological features of resistant GN BSIs in a tertiary pediatric hospital in Turkey. METHODS: Patients between 1 month and 18 years of age hospitalized between January 2005 and December 2012 were included in this study. The presence of ESBL and AmpC type beta-lactamase activity were evaluated using the Clinical and Laboratory Standards Institute (CLSI) disk diffusion and double-disk synergy tests. RESULTS: A total of 209 resistant GN bacterial BSI episodes were identified in 192 patients. Of 192 children, 133 (69.2%) were aged <=48 months of age. Sixty-six (31.6%) of the BSIs were considered community-acquired and 143 (68.4%) were hospital-acquired infections. The most common isolates were non fermenting GN bacteria (n=117, 55.9%). The major causative pathogens were Pseudomonas spp. in non-fermenting GN bacteria. The resistance rates to imipenem for Pseudomonas spp. and Acinetobacter spp. were 40.5% and 41.6%, respectively. The most common isolates in fatal patients were Pseudomonas spp. followed by Escherichia coli. The overall 28-day mortality rate was 16.3%. CONCLUSIONS: Although our study was performed at a single center and represents a local population, based on this study, it is concluded that surveillance programs and studies of novel antibiotics for resistant GN bacteria focusing on pediatric patients are required. PMID- 27185276 TI - Detection of vasostatin-1-specific CD8(+) T cells in non-obese diabetic mice that contribute to diabetes pathogenesis. AB - Chromogranin A (ChgA) is an antigenic target of pathogenic CD4(+) T cells in a non-obese diabetic (NOD) mouse model of type 1 diabetes (T1D). Vasostatin-1 is a naturally processed fragment of ChgA. We have now identified a novel H2-K(d) restricted epitope of vasostatin-1, ChgA 36-44, which elicits CD8(+) T cell responses in NOD mice. By using ChgA 36-44/K(d) tetramers we have determined the frequency of vasostatin-1-specific CD8(+) T cells in pancreatic islets and draining lymph nodes of NOD mice. We also demonstrate that vasostatin-1-specific CD4(+) and CD8(+) T cells constitute a significant fraction of islet-infiltrating T cells in diabetic NOD mice. Adoptive transfer of T cells from ChgA 36-44 peptide-primed NOD mice into NOD/severe combined immunodeficiency (SCID) mice led to T1D development. These findings indicate that vasostatin-1-specific CD8(+) T cells contribute to the pathogenesis of type 1 diabetes in NOD mice. PMID- 27185278 TI - Generation of human haploid embryonic stem cells from parthenogenetic embryos obtained by microsurgical removal of male pronucleus. PMID- 27185279 TI - High-sensitivity chemiluminescent immunoassay investigation and application for the detection of T-2 toxin and major metabolite HT-2 toxin. AB - BACKGROUND: T-2 toxin is a widely distributed mycotoxin in cereals. HT-2 toxin is the major metabolite, which is also a contaminant in cereals. T-2 toxin and HT-2 toxin have been identified as having carcinogenic, hepatotoxic, teratogenic and immunotoxic properties. To reduce the risk of contamination, a rapid, highly sensitive and inexpensive assay for the detection is required. RESULTS: In this study a high-sensitivity chemiluminescent enzyme-linked immunoassay (CL-ELISA) of T-2 toxin and HT-2 toxin was developed. With the help of the chemiluminescent substrate, this protocol showed a highly sensitive character with an IC50 as low as 33.28 ng mL-1 and 27.27 ng mL-1 for T-2 and HT-2, respectively. In addition, this method had no cross-reaction with other structurally related mycotoxins. CONCLUSION: These results indicated that the developed CL-ELISA could be applied for the detection of T-2 toxin and HT-2 toxin in actual samples without complicated steps. (c) 2016 Society of Chemical Industry. PMID- 27185277 TI - Reduced levels of dopamine and altered metabolism in brains of HPRT knock-out rats: a new rodent model of Lesch-Nyhan Disease. AB - Lesch-Nyhan disease (LND) is a severe neurological disorder caused by loss-of function mutations in the gene encoding hypoxanthine phosphoribosyltransferase (HPRT), an enzyme required for efficient recycling of purine nucleotides. Although this biochemical defect reconfigures purine metabolism and leads to elevated levels of the breakdown product urea, it remains unclear exactly how loss of HPRT activity disrupts brain function. As the rat is the preferred rodent experimental model for studying neurobiology and diseases of the brain, we used genetically-modified embryonic stem cells to generate an HPRT knock-out rat. Male HPRT-deficient rats were viable, fertile and displayed normal caged behaviour. However, metabolomic analysis revealed changes in brain biochemistry consistent with disruption of purine recycling and nucleotide metabolism. Broader changes in brain biochemistry were also indicated by increased levels of the core metabolite citrate and reduced levels of lipids and fatty acids. Targeted MS/MS analysis identified reduced levels of dopamine in the brains of HPRT-deficient animals, consistent with deficits noted previously in human LND patients and HPRT knock out mice. The HPRT-deficient rat therefore provides a new experimental platform for future investigation of how HPRT activity and disruption of purine metabolism affects neural function and behaviour. PMID- 27185280 TI - Regulation of Irregular Neuronal Firing by Autaptic Transmission. AB - The importance of self-feedback autaptic transmission in modulating spike-time irregularity is still poorly understood. By using a biophysical model that incorporates autaptic coupling, we here show that self-innervation of neurons participates in the modulation of irregular neuronal firing, primarily by regulating the occurrence frequency of burst firing. In particular, we find that both excitatory and electrical autapses increase the occurrence of burst firing, thus reducing neuronal firing regularity. In contrast, inhibitory autapses suppress burst firing and therefore tend to improve the regularity of neuronal firing. Importantly, we show that these findings are independent of the firing properties of individual neurons, and as such can be observed for neurons operating in different modes. Our results provide an insightful mechanistic understanding of how different types of autapses shape irregular firing at the single-neuron level, and they highlight the functional importance of autaptic self-innervation in taming and modulating neurodynamics. PMID- 27185281 TI - Pten Cell Autonomously Modulates the Hematopoietic Stem Cell Response to Inflammatory Cytokines. AB - Pten negatively regulates the phosphatidylinositol 3-kinase (PI3K) pathway and is required to maintain quiescent adult hematopoietic stem cells (HSCs). Pten has been proposed to regulate HSCs cell autonomously and non-cell autonomously, but the relative importance of each mechanism has not been directly tested. Furthermore, the cytokines that activate the PI3K pathway upstream of Pten are not well defined. We sought to clarify whether Pten cell autonomously or non-cell autonomously regulates HSC mobilization. We also tested whether Pten deficiency affects the HSC response to granulocyte colony-stimulating factor (G-CSF) and interferon-alpha (IFNalpha) since these cytokines induce HSC mobilization or proliferation, respectively. We show that Pten regulates HSC mobilization and expansion in the spleen primarily via cell-autonomous mechanisms. Pten-deficient HSCs do not require G-CSF to mobilize, although they are hyper-sensitized to even low doses of exogenous G-CSF. Pten-deficient HSCs are similarly sensitized to IFNalpha. Pten therefore modulates the HSC response to inflammatory cytokines. PMID- 27185283 TI - Single Targeted Exon Mutation Creates a True Congenic Mouse for Competitive Hematopoietic Stem Cell Transplantation: The C57BL/6-CD45.1(STEM) Mouse. AB - Defining the molecular regulators of hematopoietic stem and progenitor cells (HSPCs) requires in vivo functional analyses. Competitive bone marrow transplants (BMTs) compare control and test HSPCs to demonstrate the functional role of a genetic change or chemical perturbation. Competitive BMT is enabled by antibodies that specifically recognize hematopoietic cells from congenic mouse strains due to variants of the cell surface protein CD45, designated CD45.1 and CD45.2. The current congenic competitor strain, B6.SJL-Ptprc(a) Pepc(b)/BoyJ (CD45.1), has a substantial inherent disadvantage in competition against the C57BL/6 (CD45.2) strain, confounding experimental interpretation. Despite backcrossing, the congenic interval over which the B6.SJL-Ptprc(a) Pepc(b)/BoyJ strain differs is almost 40 Mb encoding ~300 genes. Here, we demonstrate that a single amino acid change determines the CD45.1 epitope. Further, we report on the single targeted exon mutant (STEM) mouse strain, CD45.1(STEM), which is functionally equivalent to CD45.2 cells in competitive BMT. This strain will permit the precise definition of functional roles for candidate genes using in vivo HSPC assays. PMID- 27185284 TI - Outcomes of intensity-modulated radiotherapy as primary treatment for oropharyngeal squamous cell carcinoma - a European singleinstitution analysis. AB - OBJECTIVES: To analyse survival and toxicity outcomes in patients treated with primary intensity-modulated radiotherapy (IMRT) for oropharyngeal squamous cell carcinoma (OPSCC) in the era of routine human papilloma virus (HPV) testing. DESIGN: Single-institution case series. SETTING: Tertiary Head and Neck Cancer Unit. PARTICIPANTS: A total of 186 patients received IMRT (+/- chemotherapy) for radical primary treatment of OPSCC between March 2010 and December 2013. HPV status was available for 88% of cases. Median radiation dose was 65 Gy in 30 daily fractions. 90% of stage III/IV patients received concurrent chemotherapy or cetuximab. MAIN OUTCOME MEASURES: Overall, disease-free and disease-specific survival; rates of late xerostomia and dysphagia. RESULTS: A total of 177 patients completed treatment (Stage I/II: 23; Stage III/IV: 154), with median follow-up of 26 months. Estimated 3-year overall survival (OS), disease-free survival (DFS) and disease-specific survival (DSS) rates were 77.2% (70.5-83.9), 72.3% (65.4-79.2) and 80.2% (74.1-86.3). Estimated 3-year OS, DFS and DSS for HPV positive patients were 90.9% (85.2-96.6), 87.9% (81.4-94.4) and 91.8% (86.3 97.3). A previously identified risk stratification method was validated, showing improved OS for low-risk over high-risk patients (HR 0.09, P < 0.001). The 2-year feeding tube retention rate was 6%, and 2-year grade >=2 xerostomia rate was 38% (23% if mean contralateral parotid dose <24 Gy). CONCLUSIONS: Outcomes with IMRT are favourable, particularly in the HPV-positive patient group. This data further supports the use of a previously described prognostication model that can be used to select patients for escalation/de-escalation clinical trials. PMID- 27185285 TI - Revealing martensitic transformation and alpha/beta interface evolution in electron beam melting three-dimensional-printed Ti-6Al-4V. AB - As an important metal three-dimensional printing technology, electron beam melting (EBM) is gaining increasing attention due to its huge potential applications in aerospace and biomedical fields. EBM processing of Ti-6Al-4V as well as its microstructure and mechanical properties were extensively investigated. However, it is still lack of quantitative studies regarding its microstructural evolution, indicative of EBM thermal process. Here, we report alpha' martensitic transformation and alpha/beta interface evolution in varied printing thicknesses of EBM-printed Ti-6Al-4V block samples by means of atom probe tomography. Quantitative chemical composition analysis suggests a general phase transformation sequence. By increasing in-fill hatched thickness, elemental partitioning ratios arise and beta volume fraction is increased. Furthermore, we observe kinetic vanadium segregation and aluminum depletion at interface front and the resultant alpha/beta interface widening phenomenon. It may give rise to an increased alpha/beta lattice mismatch and weakened alpha/beta interfaces, which could account for the degraded strength as printing thickness increases. PMID- 27185282 TI - Setting Global Standards for Stem Cell Research and Clinical Translation: The 2016 ISSCR Guidelines. AB - The International Society for Stem Cell Research (ISSCR) presents its 2016 Guidelines for Stem Cell Research and Clinical Translation (ISSCR, 2016). The 2016 guidelines reflect the revision and extension of two past sets of guidelines (ISSCR, 2006; ISSCR, 2008) to address new and emerging areas of stem cell discovery and application and evolving ethical, social, and policy challenges. These guidelines provide an integrated set of principles and best practices to drive progress in basic, translational, and clinical research. The guidelines demand rigor, oversight, and transparency in all aspects of practice, providing confidence to practitioners and public alike that stem cell science can proceed efficiently and remain responsive to public and patient interests. Here, we highlight key elements and recommendations in the guidelines and summarize the recommendations and deliberations behind them. PMID- 27185286 TI - A meta-analysis of non-invasive brain stimulation and autonomic functioning: Implications for brain-heart pathways to cardiovascular disease. AB - Given the intrinsic connection between the brain and the heart, a recent body of research emerged with the aim to influence cardiovascular system functioning by non-invasive brain stimulation (NIBS) methods such as repetitive transcranial magnetic stimulation and transcranial direct current stimulation. Despite the implications of cardiovascular activity modulation for therapeutic purposes, such effects of NIBS have not yet been quantified. The aim of this study was to meta analyze studies on NIBS effects on blood pressure (BP), heart rate (HR) and its variability (HRV). PubMed and Scopus databases were searched for English language studies conducted in humans. Twenty-nine studies were eligible for the analyses. Pooled effect sizes (Hedges' g) were compared. Random effect models were used. NIBS was effective in reducing HR (g=0.17) and enhancing HRV (g=0.30). A marginal effect emerged for BP (g=0.21). Significant moderators were the stimulation technique and the site of stimulation. Results show that NIBS affects cardiovascular and autonomic nervous system activity, confirming a potential pathogenic brain-heart pathway to cardiovascular disease. PMID- 27185287 TI - The HLA-DRB1*15 phenotype is associated with multiple red blood cell and HLA antibody responsiveness. AB - BACKGROUND: Once a patient has produced a red blood cell (RBC) antibody, there is an increased risk of additional antibody formation after subsequent RBC exposure. Recently, we observed that HLA-DRB1*15 was overrepresented in 379 multiple RBC antibody responders compared to controls or 562 patients with a single RBC antibody (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.3-2.3). In this study we evaluated whether the HLA-DRB1*15 represents a responder phenotype against HLA and/or RBC antigens. STUDY DESIGN AND METHODS: HLA-DRB1*15 frequencies in single and multiple antibody responders were compared between three groups of individuals: 1) those with HLA antibodies, 2) those with RBC antibodies, and 3) those with both RBC and HLA antibodies. RESULTS: A total of 3959 immunized patients (female-to-male ratio, 2.3) had been HLA-DRB1 typed. Among the 3275 individuals with HLA antibodies, the frequency of the DRB1*15 phenotype differed significantly from 19.7% in patients with a panel reactivity (PRA) of not more than 20% to 26.9% in patients with PRA of more than 80% (OR, 1.5; 95% CI, 1.2-1.9). This association between DRB1*15 and multiresponsiveness was mainly due to pregnancy-induced HLA immunization. In the 257 individuals with RBC and HLA antibodies, the frequency of DRB1*15 was 4.2 times (95% CI, 1.1-16) higher in those with multiple RBC antibodies and HLA-PRA of more than 50% compared to only single RBC responders with PRA of less than 20%. CONCLUSION: The HLA-DRB1*15 phenotype is associated with broad RBC and HLA immunization. PMID- 27185288 TI - 'Strengthening the fungal cell wall through chitin-glucan cross-links: effects on morphogenesis and cell integrity'. AB - The cross-linking of polysaccharides to assemble new cell wall in fungi requires transglycosylation mechanisms by which preexisting glycosidic linkages are broken and new linkages are created between the polysaccharides. The molecular mechanisms for these processes, which are essential for fungal cell biology, are only now beginning to be elucidated. Recent development of in vivo and in vitro biochemical approaches has allowed characterization of important aspects about the formation of chitin-glucan covalent cell wall cross-links by cell wall transglycosylases of the CRH family and their biological function. Covalent linkages between chitin and glucan mediated by Crh proteins control morphogenesis and also play important roles in the remodeling of the fungal cell wall as part of the compensatory responses necessary to counterbalance cell wall stress. These enzymes are encoded by multigene families of redundant proteins very well conserved in fungal genomes but absent in mammalian cells. Understanding the molecular basis of fungal adaptation to cell wall stress through these and other cell wall remodeling enzymatic activities offers an opportunity to explore novel antifungal treatments and to identify potential fungal virulence factors. PMID- 27185289 TI - The mental well-being of Central American transmigrant men in Mexico. AB - To understand the mental health status of Central American migrant men travelling through Mexico to the U.S., we analysed the association between migration-related circumstances/stressors and psychological disorders. In-person interviews and a psychiatric assessment were conducted in 2010 and 2014 with 360 primarily Honduran transmigrant young adult males. The interviews were conducted at three Casas del Migrante (or migrant safe houses) in the migration-corridor cities of Monterrey, and Guadalupe, Nuevo Leon; and Saltillo, Coahuila. The results indicated high levels of migration-related stressors including abuse and a high prevalence of major depressive episodes (MDEs), alcohol dependency, and alcohol abuse. Nested logistic regression models were used to separately predict MDEs, alcohol dependency, and alcohol abuse, assessing their association with migration experiences and socio-demographic characteristics. Logistic regression models showed that characteristics surrounding migration (experiencing abuse, migration duration, and attempts) are predictive of depression. Alcohol dependency and abuse were both associated with marital status and having family/friends in the intended U.S. destination, while the number of migration attempts also predicted alcohol dependency. The results provide needed information on the association between transit migration through Mexico to the U.S. among unauthorised Central American men and major depressive disorder and alcohol abuse and dependency. PMID- 27185290 TI - Access to Spiro and Fused Indole Derivatives from alpha,beta-Unsaturated Aldehydes Enabled by N-Heterocyclic Carbene Catalysis. AB - Spiro and fused indoles are attractive heterocyclic compounds with broad and promising activities in various therapeutic fields, and thus, have become the synthetic targets of organic chemists. In this account, we describe our recent progress in the synthesis of a series of spiro and fused indole derivatives through N-heterocyclic carbene (NHC)-catalyzed annulations of diverse NHC-bound intermediates derived from alpha,beta-unsaturated aldehydes. Particularly, the novel synthesized isatin-derived alpha-bromoenals may be used as versatile 1,3 biselectrophile synthons for combination with a range of bisnucleophiles for potentially divergent syntheses of skeletally diverse spirooxindoles in the future. PMID- 27185293 TI - Theory of the development of curved barbs and their effects on feather morphology. AB - Feathers exhibit an extraordinary diversity of shapes, which are used by birds to accomplish a diverse set of functions. Pennaceous feathers have a double branched morphology that develops from a tube of epidermis, and variation in branch geometry determines feather shape. Feather development is both complex (i.e., a simple developmental modification can have multiple effects on mature feather shape), and redundant (i.e., different developmental modifications can create the same shape). Due to this, it is not readily apparent how different feather shapes develop. In many feathers, barbs are not straight, but instead curve in toward, or away, from the feather tip. Barb curvature can affect the shape of mature feathers but the development of curved barbs is unknown. Previous research has hypothesized that barb curvature could develop either during the helical growth of barb ridges in the tubular feather germ, or during barb angle expansion as the feather unfurls from the sheath. To better understand the development of curved barbs and their effects on mature feathers we present a theoretical model of curved barb development and test the model with empirical investigations of feathers. We find that curved barbs affect many aspects of feather morphology including vane width, barb length, and barb spacing. In real feathers, curved barbs can develop both during helical barb ridge growth and during barb angle expansion, with most of the observed curvature due to barb angle expansion. Our results demonstrate that barb angle expansion as a feather unfurls from the sheath is a complex and dynamic process that plays an important role in determining the shape and structure of mature feathers. Curved barbs create heterogeneity in barb geometry within the feather vane, which could have important implications for aerodynamic function and the development of within feather pigmentation patterns. J. Morphol. 277:995-1013, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27185292 TI - In vivo organ specific drug delivery with implantable peristaltic pumps. AB - Classic methods for delivery of agents to specific organs are technically challenging and causes superfluous stress. The current study describes a method using programmable, implantable peristaltic pumps to chronically deliver drugs in vivo, while allowing animals to remain undisturbed for accurate physiological measurements. In this study, two protocols were used to demonstrate accurate drug delivery to the renal medulla. First, the vasopressin receptor-2 agonist, dDAVP, was delivered to the renal medulla resulting in a significant increase in water retention, urine osmolality and aquaporin-2 expression and phosphorylation. Second, in a separate group of rats, the histone deacetylase (HDAC) inhibitor, MS275, was delivered to the renal medulla. HDAC inhibition resulted in a significant increase in histone H3-acetylation, the hallmark for histone deacetylase inhibition. However, this was confined to the medulla, as the histone H3-acetylation was similar in the cortex of vehicle and MS275 infused rats, suggesting targeted drug delivery without systemic spillover. Thus, implantable, peristaltic pumps provide a number of benefits compared to externalized chronic catheters and confer specific delivery to target organs. PMID- 27185294 TI - Tests of manual dexterity and speed in Parkinson's disease: Not all measure the same. AB - INTRODUCTION: Timed performance tests were introduced to overcome the disadvantages of subjective evaluation of bradykinesia in Parkinson's disease (PD). We aimed to verify their discriminative properties and compare them with the motion capture analysis of finger tapping. METHODS: We included 22 PD patients (10 M, 12 F), mean age 64 (range 48-82) yrs, Hoehn & Yahr stage 2 (1 2.5) and 22 (10 M, 12 F) normal controls, mean age 66 (41-82) yrs. The key tapping subtest of the Halstead-Reitan battery, the Purdue Pegboard test, and the Bradykinesia-Akinesia Incoordination (BRAIN) test were performed according to the test manuals. The finger tapping subtest of the UPDRS-III, item 23 was recorded using a contactless 3D motion capture system Optitrack-V120. Average frequency (AvgFrq), maximum opening velocity (MaxOpV) and amplitude decrement (AmpDec) were computed and simultaneous video recordings of finger tapping were rated by two experts. RESULTS: The AmpDec and MaxOpV motion capture measures best differentiated between PD patients and controls (AUC = 0.87 and 0.81). Of the instrumental tests, only the Purdue Pegboard attained significance in differentiating PD patients from controls (AUC = 0.80). In PD patients, MaxOpV correlated with the finger tapping ratings and BRAIN test, and AvgFrq correlated with the BRAIN and Halstead-Reitan test scores. Moreover, correlations were found between the Purdue Pegboard and finger tapping ratings. CONCLUSIONS: Contactless 3D motion capture of finger tapping allowed an independent analysis of individual components of bradykinesia, demonstrating the amplitude decrement and maximum opening velocity as the most powerful discriminators between PD patients and controls. PMID- 27185291 TI - Development and characterization of synthetic antibodies binding to the cystic fibrosis conductance regulator. AB - Cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel in the apical surface of epithelial cells in the airway and gastrointestinal tract, and mutation of CFTR is the underlying cause of cystic fibrosis. However, the precise molecular details of the structure and function of CFTR in native and disease states remains elusive and cystic fibrosis researchers are hindered by a lack of high specificity, high affinity binding reagents for use in structural and biological studies. Here, we describe a panel of synthetic antigen-binding fragments (Fabs) isolated from a phage-displayed library that are specific for intracellular domains of CFTR that include the nucleotide-binding domains (NBD1 and NBD2), the R-region, and the regulatory insertion loop of NBD1. Binding assays performed under conditions that promote the native fold of the protein demonstrated that all Fabs recognized full-length CFTR. However, only the NBD1 specific Fab recognized denatured CFTR by western blot, suggesting a conformational epitope requirement for the other Fabs. Surface plasmon resonance experiments showed that the R-region Fab binds with high affinity to both the phosphorylated and unphosphorylated R-region. In addition, NMR analysis of bound versus unbound R-region revealed a distinct conformational effect upon Fab binding. We further defined residues involved with antibody recognition using an overlapping peptide array. In summary, we describe methodology complementary to previous hybridoma-based efforts to develop antibody reagents to CFTR, and introduce a synthetic antibody panel to aid structural and biological studies. PMID- 27185295 TI - The Effectiveness of Self-Management Mobile Phone and Tablet Apps in Long-term Condition Management: A Systematic Review. AB - BACKGROUND: Long-term conditions and their concomitant management place considerable pressure on patients, communities, and health care systems worldwide. International clinical guidelines on the majority of long-term conditions recommend the inclusion of self-management programs in routine management. Self-management programs have been associated with improved health outcomes; however, the successful and sustainable transfer of research programs into clinical practice has been inconsistent. Recent developments in mobile technology, such as mobile phone and tablet computer apps, could help in developing a platform for the delivery of self-management interventions that are adaptable, of low cost, and easily accessible. OBJECTIVE: We conducted a systematic review to assess the effectiveness of mobile phone and tablet apps in self-management of key symptoms of long-term conditions. METHODS: We searched PubMed, Embase, EBSCO databases, the Cochrane Library, and The Joanna Briggs Institute Library for randomized controlled trials that assessed the effectiveness of mobile phone and tablet apps in self-management of diabetes mellitus, cardiovascular disease, and chronic lung diseases from 2005-2016. We searched registers of current and ongoing trials, as well as the gray literature. We then checked the reference lists of all primary studies and review papers for additional references. The last search was run in February 2016. RESULTS: Of the 9 papers we reviewed, 6 of the interventions demonstrated a statistically significant improvement in the primary measure of clinical outcome. Where the intervention comprised an app only, 3 studies demonstrated a statistically significant improvement. Interventions to address diabetes mellitus (5/9) were the most common, followed by chronic lung disease (3/9) and cardiovascular disease (1/9). A total of 3 studies included multiple intervention groups using permutations of an intervention involving an app. The duration of the intervention ranged from 6 weeks to 1 year, and final follow-up data ranged from 3 months to 1 year. Sample size ranged from 48 to 288 participants. CONCLUSIONS: The evidence indicates the potential of apps in improving symptom management through self-management interventions. The use of apps in mHealth has the potential to improve health outcomes among those living with chronic diseases through enhanced symptom control. Further innovation, optimization, and rigorous research around the potential of apps in mHealth technology will move the field toward the reality of improved health care delivery and outcomes. PMID- 27185296 TI - Increased biofilm formation ability in Klebsiella pneumoniae after short-term exposure to a simulated microgravity environment. AB - Biofilm formation is closely related to the pathogenetic processes of Klebsiella pneumoniae, which frequently causes infections in immunocompromised individuals. The immune system of astronauts is compromised in spaceflight. Accordingly, K. pneumoniae, which used to be isolated from orbiting spacecraft and astronauts, poses potential threats to the health of astronauts and mission security. Microgravity is a key environmental cue during spaceflight. Therefore, determining its effects on bacterial biofilm formation is necessary. In this study, K. pneumoniae ATCC BAA-1705 was exposed to a simulated microgravity (SMG) environment. K. pneumoniae grown under SMG formed thicker biofilms compared with those under normal gravity (NG) control after 2 weeks of subculture. Two indicative dyes (i.e., Congo red and calcofluor) specifically binding to cellulose fibers and/or fimbriae were utilized to reconfirm the enhanced biofilm formation ability of K. pneumoniae grown under SMG. Further analysis showed that the biofilms formed by SMG-treated K. pneumoniae were susceptible to cellulase digestion. Yeast cells mannose-resistant agglutination by K. pneumoniae type 3 fimbriae was more obvious in the SMG group, which suggests that cellulose production and type 3 fimbriae expression in K. pneumoniae were both enhanced under the SMG condition. Transcriptomic analysis showed that 171 genes belonging to 15 functional categories were dysregulated in this organism exposed to the SMG conditions compared with those in the NG group, where the genes responsible for the type 3 fimbriae (mrkABCDF) and its regulator (mrkH) were upregulated. PMID- 27185298 TI - Intranasal delivery of nanoparticle encapsulated tarenflurbil: A potential brain targeting strategy for Alzheimer's disease. AB - Poor brain penetration of tarenflurbil (TFB) was one of the major reasons for its failure in phase III clinical trials conducted on Alzheimer's patients. Thus there is a tremendous need of developing efficient delivery systems for TFB. This study was designed with the aim of improving drug delivery to brain through intranasally delivered nanocarriers. TFB was loaded into two different nanocarriers i.e., poly (lactide-co-glycolide) nanoparticles (TFB-NPs) and solid lipid nanoparticles (TFB-SLNs). Particle size of both the nanocarriers (<200nm) as determined by dynamic light scattering technique and transmission electron microscopy, assured transcellular transport across olfactory axons whose diameter was ~200nm and then paving a direct path to brain. TFB-NPs and TFB-SLNs resulted in 64.11+/-2.21% and 57.81+/-5.32% entrapment efficiencies respectively which again asserted protection of drug from chemical and biological degradation in nasal cavity. In vitro release studies proved the sustained release of TFB from TFB-NPs and TFB-SLNs in comparison with pure drug, indicating prolonged residence times of drug at targeting site. Pharmacokinetics suggested improved circulation behavior of nanoparticles and the absolute bioavailabilities followed this order: TFB-NPs (i.n.)>TFB-SLNs (i.n.)>TFB solution (i.n.)>TFB suspension (oral). Brain targeting efficiency was determined in terms of %drug targeting efficiency (%DTE) and drug transport percentage (DTP). The higher %DTE (287.24) and DTP (65.18) were observed for TFB-NPs followed by TFB-SLNs (%DTE: 183.15 and DTP: 45.41) among all other tested groups. These encouraging results proved that therapeutic concentrations of TFB could be transported directly to brain via olfactory pathway after intranasal administration of polymeric and lipidic nanoparticles. PMID- 27185297 TI - Effectiveness of supersaturation promoting excipients on albendazole concentrations in upper gastrointestinal lumen of fasted healthy adults. AB - PURPOSE: To evaluate the impact of dosage form relevant levels of a polymeric precipitation inhibitor and of lipid excipients on supersaturation of upper gastrointestinal contents with albendazole, a lipophilic weak base. MATERIALS AND METHODS: Albendazole concentrations in stomach and in duodenum were evaluated after administration of 1) a suspension in water (Susp-Control), 2) a suspension in water in which hydroxyprolylmethylcellulose E5 (HPMC E5) had been pre dissolved (Susp-HPMC), and 3) and 4) two contrasting designs of lipid based suspensions dispersed in water (Susp-IIIA and Susp-IV), on a cross-over basis to fasted healthy adults. RESULTS: Limited, but statistically significant supersaturation of duodenal contents was observed after Susp-HPMC, Susp-IIIA, and Susp-IV; supersaturation was more consistent after Susp-HPMC administration. Based on total albendazole amount per volume, gastric secretions did not significantly alter volumes of bulk gastric contents during the first 40min post administration of a glass of non-caloric water-based fluid. Alphalbendazole gastric concentrations were higher than in the administered suspensions, but similar for all four formulations. Gastric emptying of albendazole after administration of Susp-Control or Susp-HPMC was slower than after administration of Susp-IIIA or Susp-IV. CONCLUSIONS: Small amounts of HPMC E5 were as effective as lipid excipients in achieving supersaturation of duodenal contents with albendazole, a fast precipitating weak base, in fasted adults. However, compared with the effect of HPMC E5 the effect of lipid excipients was delayed and variable. PMID- 27185301 TI - Wang, S.-Y., Chen, W.-L., Wang, Z.-C., et al. High expression of FAMLF is associated with clinical response in patients with de novo acute myeloid leukemia. Leuk. Lymphoma 2016. http://dx.doi.org/10.3109/10428194.2016.1160087. PMID- 27185300 TI - Type I collagen and its daughter peptides for targeting mucosal healing in ulcerative colitis: A new treatment strategy. AB - Ulcerative colitis, particularly the chronic persistent form is characterized by the presence of active inflammation and extensive areas of ulceration in the colonic mucosa. The existing treatment protocol aims at only reducing intestinal inflammation, rather than targeting mucosal ulceration. In this study, type I collagen and its daughter peptides called collagen hydrolysate, highly popular reconstructive materials for tissue engineering applications, are hypothesized as healing matrices to target the recuperation of internal mucosal ulceration. The clinical assessments on day 10 of dextran sodium sulfate induced colitis in mice model revealed that both the collagen (1.56+/-0.29) and collagen hydrolysate treatments (1.33+/-0.33) showed a significant reduction in the rectal bleeding compared to the reference mesalamine treatment (2.50+/-0.33) and untreated negative control (2.40+/-0.40). VEGF, a potent angiogenic growth factor, over expressed during UC was down-regulated by collagen hydrolysate (1.06+/-0.25) and collagen (1.76+/-0.45) to a greater extent than by mesalamine (2.59+/-0.51) and untreated control (4.17+/-0.15). The down-regulation of proinflammatory cytokines such as TNF-alpha, IL-1beta, and IL-6 also follows the same pattern. Histological observations were in accordance with the clinical indicators. Both collagen and collagen hydrolysate treatments showed significant reduction in mucosal damage score and facilitated faster regeneration of damaged mucosa. PMID- 27185299 TI - Preclinical pharmacokinetics, biodistribution, radiation dosimetry and toxicity studies required for regulatory approval of a phase I clinical trial with (111)In CP04 in medullary thyroid carcinoma patients. AB - INTRODUCTION: From a series of radiolabelled cholecystokinin (CCK) and gastrin analogues, (111)In-CP04 ((111)In-DOTA-(DGlu)6-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2) was selected for further translation as a diagnostic radiopharmaceutical towards a first-in-man study in patients with medullary thyroid carcinoma (MTC). A freeze dried kit formulation for multicentre application has been developed. We herein report on biosafety, in vivo stability, biodistribution and dosimetry aspects of (111)In-CP04 in animal models, essential for the regulatory approval of the clinical trial. MATERIALS AND METHODS: Acute and extended single dose toxicity of CP04 was tested in rodents, while the in vivo stability of (111)In-CP04 was assessed by HPLC analysis of mouse blood samples. The biodistribution of (111)In CP04 prepared from a freeze-dried kit was studied in SCID mice bearing double A431-CCK2R(+/-) xenografts at 1, 4 and 24h pi. Further 4-h animal groups were either additionally treated with the plasma expander gelofusine or injected with (111)In-CP04 prepared by wet-labelling. Pharmacokinetics in healthy mice included the 30min, 1, 4, 24, 48 and 72h time points pi. Dosimetric calculations were based on extrapolation of mice data to humans adopting two scaling models. RESULTS: CP04 was well-tolerated by both mice and rats, with an LD50>178.5MUg/kg body weight for mice and a NOAEL (no-observed-adverse-effect-level) of 89MUg/kg body weight for rats. After labelling, (111)In-CP04 remained >70% intact in peripheral mouse blood at 5min pi. The uptake of (111)In-CP04 prepared from the freeze-dried kit and by wet-labelling were comparable in the A431-CCK2R(+) xenografts (9.24+/-1.35%ID/g and 8.49+/-0.39%ID/g, respectively; P>0.05). Gelofusine-treated mice exhibited significantly reduced kidneys values (1.69+/ 0.15%ID/g vs. 5.55+/-0.94%ID/g in controls, P<0.001). Dosimetry data revealed very comparable effective tumour doses for the two scaling models applied, of 0.045 and 0.044mSv/MBq. CONCLUSION: The present study has provided convincing toxicology, biodistribution and dosimetry data for prompt implementation of the freeze-dried kit formulation without or with gelofusine administration in a multicentre clinical trial in MTC patients. PMID- 27185302 TI - Characterization of cadmium-resistant bacteria for its potential in promoting plant growth and cadmium accumulation in Sesbania bispinosa root. AB - The cadmium (Cd) resistant bacteria were isolated from soils of Damanganga river, Vapi, and identified 11 potential Cd resistant bacteria based on 16S rDNA sequences. The Cd resistant bacteria belonged to four different genera: Providencia spp., Morganella sp., Stenotrophomonas sp., and Bacillus spp. The assessment of plant growth-promoting (PGP) parameters revealed that the Cd tolerant bacteria showed one or more PGP properties. Further, a pot experiment was conducted to elucidate the effects of Cd resistant bacteria on the plant growth and the uptake of Cd by Sesbania bispinosa. The bacterized seedlings recorded 36.0-74.8% and 21.2-32.9% higher root and shoot lengths, respectively, in Cd amended soil compared with control. The Cd mobilization in the root of S. bispinosa by microbial inoculants ranged from 0.02 +/- 0.01 to 1.11 +/- 0.06 ppm. The enhanced concentrations of Cd accumulation in S. bispinosa roots correspond to the effect of the bacterial strains on metal mobilization in soil. The present observations showed that the Cd resistant strains protect the plants against the inhibitory effects of Cd, probably due to the production of PGP properties. The present results provided a new insight into the phytoremediation of Cd contaminated soil. PMID- 27185303 TI - A microfluidics-based on-chip impinger for airborne particle collection. AB - Capturing airborne particles from air into a liquid is a critical process for the development of many sensors and analytical systems. A miniaturized airborne particle sampling device (microimpinger) has been developed in this research. The microimpinger relies on a controlled bubble generation process produced by driving air through microchannel arrays. The particles confined in the microscale bubbles are captured in the sampling liquid while the bubbles form, are released and travel in a millimetre-scale sealed liquid reservoir. The microchannel arrays in the impinger are fabricated using a soft-lithography method with polydimethylsiloxane (PDMS) as the structural material. To prevent air leakage at the connections, a PDMS-only sealing technique is successfully developed. The hydrophobicity of the microchannel surface is found to be critical for generating continuous and stable bubbles in the bubbling process. A Teflon layer is coated on the walls of a microchannel array by vapor deposition which effectively increases the hydrophobicity of the PDMS. The collection efficiency of the microimpinger is measured by counting different sizes of fluorescent polystyrene latex particles on polycarbonate membrane filters. Collection efficiencies above 90% are achieved. Furthermore, the particle capturing mechanisms during the injection, formation and rise of a single microbubble are investigated by a computational fluid dynamics (CFD) model. The Navier-Stokes equations are solved along with the use of the volume-of-fluid (VOF) method to capture the bubble deformations and the particles are tracked using a Lagrangian equation of motion. The model is also employed to study the effect of bubble size on the collection efficiency of the microimpinger. PMID- 27185304 TI - Intrinsic Charge Transport across Phase Transitions in Hybrid Organo-Inorganic Perovskites. AB - Hall effect measurements in CH3 NH3 PbBr3 single crystals reveal that the charge carrier mobility follows an inverse-temperature power-law dependence, MU ? T(-) (gamma) , with the power exponent gamma = 1.4 +/- 0.1 in the cubic phase, indicating an acoustic-phonon-dominated carrier scattering, and gamma = 0.5 +/- 0.1 in the tetragonal phase, suggesting another dominant mechanism, such as a piezoelectric or space-charge scattering. PMID- 27185305 TI - Robust two-dimensional superconductivity and vortex system in Bi2Te3/FeTe heterostructures. AB - The discovery of two-dimensional superconductivity in Bi2Te3/FeTe heterostructures provides a new platform for the search of Majorana fermions in condensed matter systems. Since Majorana fermions are expected to reside at the core of the vortices, a close examination of the vortex dynamics in superconducting interface is of paramount importance. Here, we report the robustness of the interfacial superconductivity and 2D vortex dynamics in four as grown and aged Bi2Te3/FeTe heterostructure with different Bi2Te3 epilayer thickness (3, 5, 7, 14 nm). After two years' air exposure, superconductivity remains robust even when the thickness of Bi2Te3 epilayer is down to 3 nm. Meanwhile, a new feature at ~13 K is induced in the aged samples, and the high field studies reveal its relevance to superconductivity. The resistance of all as grown and aged heterostructures, just below the superconducting transition temperature follows the Arrhenius relation, indicating the thermally activated flux flow behavior at the interface of Bi2Te3 and FeTe. Moreover, the activation energy exhibits a logarithmic dependence on the magnetic field, providing a compelling evidence for the 2D vortex dynamics in this novel system. The weak disorder associated with aging-induced Te vacancies is possibly responsible for these observed phenomena. PMID- 27185307 TI - Application of diffusion kurtosis imaging to odontogenic lesions: Analysis of the cystic component. AB - PURPOSE: To assess the feasibility of applying diffusion kurtosis imaging (DKI) to common odontogenic lesions and to compare its diagnostic ability versus that of the apparent diffusion coefficient (ADC) for differentiating keratocystic odontogenic tumors (KCOTs) from odontogenic cysts. MATERIALS AND METHODS: Altogether, 35 odontogenic lesions were studied: 24 odontogenic cysts, six KCOTs, and five ameloblastomas. The diffusion coefficient (D) and excessive kurtosis (K) were obtained from diffusion-weighted images at b-values of 0, 500, 1000, and 1500 s/mm2 on 3T magnetic resonance imaging (MRI). The combination of D and K values showing the maximum density of the probable density function was estimated. The ADC was obtained (0 and 1000 s/mm2 ). Values for odontogenic cysts, KCOTs, and ameloblastomas were compared. Multivariate logistic regression modeling was performed to assess the combination of D and K model versus ADC for differentiating KCOTs from odontogenic cysts. RESULTS: The mean D and ADC were significantly higher for ameloblastomas than for odontogenic cysts or KCOTs (P < 0.05). The mean K was significantly lower for ameloblastomas than for odontogenic cysts or KCOTs (P < 0.05). The mean values of all parameters for odontogenic cysts and KCOTs showed no significant differences (P = 0.369 for ADC, 0.133 for D, and 0.874 for K). The accuracy of the combination of D and K model (76.7%) was superior to that of ADC (66.7%). CONCLUSION: Use of DKI may be feasible for common odontogenic lesions. A combination of DKI parameters can be expected to increase the accuracy of its diagnostic ability compared with ADC. J. Magn. Reson. Imaging 2016;44:1565-1571. PMID- 27185308 TI - A French adaptation of the Overt Behaviour Scale (OBS) measuring challenging behaviours following acquired brain injury: The Echelle des comportements observables (ECO). AB - PURPOSE: To develop a French version of the Overt Behaviour Scale (OBS) and examine some of its psychometric properties. METHODS: The scale was adapted and validated according to standard guidelines for cross-cultural adaptation of questionnaires (Echelle des comportements observables; ECO). The reliability and construct validity of the ECO were studied among 29 inpatients and outpatients who sustained an acquired brain injury. The instruments were administered by 12 clinicians located at eight rehabilitation centres and the local brain injury association. RESULTS: The ECO provided behaviour profile descriptives much like the original scale. It showed excellent reliability and good convergent and divergent validity, as reflected by significant associations with other measures that contained similar behavioural items and by the absence of signification correlations with broader constructs such as physical and cognitive abilities. CONCLUSION: This study provides evidence that the ECO behaves much like the original OBS, has promising initial findings with respect to reliability and validity and is a valuable research and clinical instrument to assess the severity and typology of challenging behaviour after an acquired brain injury and to monitor the evolution of behaviours after intervention in French and bilingual communities. PMID- 27185309 TI - Simple Spinning of Heterogeneous Hollow Microfibers on Chip. AB - A novel and simple chip-based microfluidic strategy is proposed for continuously controlled spinning of desirable hollow microfibers. These fabricated fiber shaped materials exhibit extraordinary morphological and structural complexity, as well as a heterogeneous composition. The resulting specific hollow microfibers have potential applications in numerous chemical and biomedical fields. PMID- 27185312 TI - Depression and resting state heart rate variability in children and adolescents - A systematic review and meta-analysis. AB - Among adults, depression is associated with reduced vagal activity, as indexed by high frequency heart rate variability [HF-HRV]), which correlates inversely with depression severity. Available evidence in depressed children and adolescents remains to be reviewed systematically. A search of the literature was performed to identify studies reporting (i) HF-HRV in clinically depressed children/adolescents relative to controls (k=4, n=259) and (ii) the association between HF-HRV and depressive symptoms as measured by standardized psychometric instruments in children and adolescents (k=6, n=2625). Random-effects meta analysis on group differences revealed significant effects that were associated with a moderate effect size (Hedges' g=-0.59; 95% CI [-1.05; -0.13]), indicating lower resting state HF-HRV among clinically depressed children/adolescents (n=99) compared to healthy controls (n=160), consistent with findings among adults. While no correlation between HF-HRV and depressive symptom severity was observed (r=-.041 [-0.143; 0.062]), these additional correlational findings are limited to non-clinical samples. Findings have important clinical implications including a potentially increased risk for future physical ill health and also the identification of potential new treatment targets in child and adolescent depression. PMID- 27185313 TI - Combining bottom-up and top-down approaches for knowledge discovery: Comment on "Towards a unified approach in the modeling of fibrosis: A review with research perspectives" by Martine Ben Amar and Carlo Bianca. PMID- 27185314 TI - ODEs approaches in modeling fibrosis: Comment on "Towards a unified approach in the modeling of fibrosis: A review with research perspectives" by Martine Ben Amar and Carlo Bianca. PMID- 27185315 TI - Biological systems modeling in the context of fibrosis: Comment on "Towards a unified approach in the modeling of fibrosis: A review with research perspectives" by Martine Ben Amar and Carlo Bianca. PMID- 27185316 TI - Calsequestrin-1 Regulates Store-Operated Ca2+ Entry by Inhibiting STIM1 Aggregation. AB - BACKGROUND/AIMS: Stromal interacting molecule-1 (STIM1) aggregation and redistribution to plasma membrane to interact with Orai1 constitute the core mechanism of store-operated Ca2+ entry (SOCE). Previous study has revealed that calsequestrin-1 (CSQ1) regulates SOCE in HEK293 cells through interacting with STIM1 and inhibiting STIM1/Orai1 interaction. Here, we further investigate how CSQ1/STIM1 interaction affects SOCE. METHODS: Using confocal microscopy, STIM1 aggregation and co-localizations with CSQ1 or Orai1 upon Ca2+ store depletion by thapsigargin were measured and quantified by Imaris software in HeLa cells transfected with different CSQ1 mutants. The interactions of CSQ1/STIM1 and STIM1/Orai1, and internal Ca2+ changes were detected by co-immunoprecipitation and Fura2, respectively. RESULTS: Wt-CSQ1 overexpression significantly reduced STIM1 clustering in the perimembrane and cytosolic regions, whereas over expression of a C-terminal amino acid 362-396 deletion mutant (C35) did not. Consistently, a significant depression of SOCE, increased CSQ1 monomerization and CSQ1/STIM1 interaction, and a reduced STIM1/Orai1 association were observed in wt CSQ1 but not in C35-transfected cells. Additionally, mutant lacking C-terminal AA 388-396 deletion exerted weaker potency in inhibiting STIM1 aggregation and association with Orai1 than wt-CSQ1. CONCLUSIONS: Our results demonstrate that CSQ1 monomers suppress SOCE by interacting with STIM1 and attenuating STIM1 aggregation via its C-terminal amino acid 362-396. PMID- 27185317 TI - Is there such a thing as sustainable physical activity? AB - There is a global need to diminish climate gas emissions, and a simultaneous call for enhanced levels of physical activity. Increased physical activity entails reduced risk for overweight and chronic diseases, as well as a potential to reduce transport's major contribution to global CO2 emissions. However, increased physical activity level also implies increased energy expenditure. Therefore, we aim to introduce the concept of sustainable physical activity, and to suggest certain physical activity habits due to their potentially sustainable properties. Worldwide, a third of adults and four fifths of adolescents ought to be more physically active in order to comply with current physical activity recommendations. Yet, considering upcoming resource challenges, types of physical activity should be taken into account. Active transportation represents carbon friendly means of transportation as well as an opportunity for enhanced physical activity. Physical activity conducted in the local community is likely to favor sustainability through less use of fossil fuel, as it makes transportation redundant. Moreover, going "back to basic", using less equipment and appliances for everyday tasks could contribute toward energy balance through increased physical activity, and could decrease resource use. Finally, balancing food intake and energy expenditure would require less food production with accompanying energy savings. PMID- 27185318 TI - Sexual activity and dyspareunia the first year postpartum in relation to degree of perineal trauma. AB - INTRODUCTION AND HYPOTHESIS: Knowledge on sexual complaints and time to sexual resumption after obstetric anal sphincter injury (OASI) is scarce. The aim of the study was to investigate self-reported sexual activity and coital problems 1 year postpartum in relation to perineal trauma, in addition to delivery mode. METHODS: Among 2,846 women recruited during pregnancy, all women who delivered with OASI (n = 42, all third-degree perineal tears), in addition to 20 randomly selected controls per OASI case, a total of 882 women, were sent a self-administered questionnaire addressing time to coital resumption after delivery and potential coital difficulty 1 year postpartum. RESULTS: By 8 weeks, half of the 561 responders (51.4 %) had resumed intercourse, increasing to 75.2 % by 12 weeks and 94.7 % 1 year postpartum. In multivariate regression analysis OASI was the strongest predictor for postponed coital onset, defined as after 8 weeks (aOR 5.52, CI 1.59-19.16). OASI was also the only significant predictor for dyspareunia 1 year after delivery (aOR 3.57, CI 1.39-9.19). Episiotomy was neither a risk factor for postponed coital onset nor for dyspareunia. There were no differences between episiotomy and second-degree laceration injury groups regarding postponed coital onset (p = 0.45) or dyspareunia (p = 0.67) 1 year postpartum. CONCLUSIONS: Obstetric anal sphincter injury was a strong and independent predictor for both postponed coital resumption after delivery and for dyspareunia 1 year postpartum, whereas episiotomy and spontaneous second-degree lacerations were not. Our main finding of affected sexual activity after OASI further supports the need to reduce the rates of this obstetric injury to a minimum. PMID- 27185321 TI - Father's age and lifestyle link to birth defects in offspring, review finds. PMID- 27185320 TI - Pediatrician preferences, local resources, and economic factors influence referral to a subspecialty access clinic. AB - BACKGROUND: Pediatric patients seek timely access to subspecialty care within a complex delivery system while facing barriers: distance, economics, and clinician shortages. Aim We examined stakeholder perceptions about solutions to the access challenge. We engaged over 300 referring primary care pediatricians in the evaluation of Access Clinics at an academic children's hospital. METHODS: Using an anonymous online survey, we asked pediatricians about their and their patients' experiences and analyzed factors that may influence referrals. Findings Referring pediatricians reported satisfaction; they provided feedback about their patients' experiences, physician communication, and referral influences. Distance from the Access Clinic does not correlate with differences in referral volume; living in areas with higher child populations and higher median income is associated with more referrals. Referring pediatricians have strong opinions about referrals, are attuned to patient experiences, and desire bi-directional communication. Multiple factors influence referral to and acceptance of Access Clinics, but external influences have less impact than expected. PMID- 27185319 TI - Supercritical Fluid Extraction of Citrus iyo Hort. ex Tanaka Pericarp Inhibits Growth and Induces Apoptosis Through Abrogation of STAT3 Regulated Gene Products in Human Prostate Cancer Xenograft Mouse Model. AB - Activation of signal transducer and activator of transcription 3 (STAT3) is well known to play a major role in the cell growth, survival, proliferation, metastasis, and angiogenesis of various cancer cells. Most of the citrus species offer large quantities of phytochemicals that have beneficial effects attributed to their chemical components. Our study was carried out to evaluate the anticancer effects of the pericarp of Iyokan ( Citrus iyo Hort. ex Tanaka), locally known as yeagam in Korea, through modulation of the STAT3 signaling pathway in both tumor cells and a nude mice model. The effect of supercritical extracts of yeagam peel (SEYG) on STAT3 activation, associated protein kinases, STAT3-regulated gene products, cellular proliferation, and apoptosis was examined. The in vivo effect of SEYG on the growth of DU145 human prostate xenograft tumors in athymic nu/nu male mice was also investigated. We found SEYG exerted substantial inhibitory effect on STAT3 activation in human prostate cancer DU145 cells as compared to other tumor cells analyzed. SEYG inhibited proliferation and downregulated the expression of various STAT3-regulated gene products such as bcl-2, bcl-xL, survivin, IAP-1/2, cyclin D1, cyclin E, COX-2, VEGF, and MMP-9. This correlated with an increase in apoptosis as indicated by an increase in the expression of p53 and p21 proteins, the sub-G1 arrest, and caspase-3-induced PARP cleavage. When administered intraperitoneally, SEYG reduced the growth of DU145 human prostate xenograft tumors through downmodulation of STAT3 activation in athymic nu/nu male mice. Overall, these results suggest that SEYG extract has the potential source of STAT3 inhibitors that may have a potential in chemoprevention of human prostate cancer cells. PMID- 27185322 TI - Internalized Homonegativity, Sense of Belonging, and Depressive Symptoms Among Australian Gay Men. AB - Internalized homonegativity has been directly linked to depression among gay men. The aim of the study was to test whether internalized homonegativity is indirectly related to depressive symptoms via a sense of belonging to the broad gay community, gay groups, gay friends, and the general community. A sample of 246 self-identified Australian gay men, aged 18-82 years, completed the Internalized Homophobia Scale, the Psychological subscale of the Sense of Belonging Instrument, the Sense of Belonging Within Gay Communities Scale, and the Centre for Epidemiological Studies Depression Scale. Results indicated that the final model was an excellent fit to the data. Internalized homonegativity was indirectly related to depressive symptoms via sense of belonging to gay groups, with gay friends, and to the general community. Interventions aimed at reducing internalized homonegativity among gay men have the potential to enhance sense of belonging and, in turn, decrease depressive symptoms. PMID- 27185324 TI - Peritonitis in children with automated peritoneal dialysis: a single-center study of a 10-year experience. AB - Peritoneal dialysis (PD) constitutes the preferred dialysis modality for children requiring renal replacement therapy with peritonitis being one of the most common complications of PD. This study was performed to evaluate the epidemiology, microbiology, and outcomes of PD-associated peritonitis in Greek children for a 10-year period. A total of 27 patients (16 males) with a mean age 121.8 +/- 57.2 months were retrospective analyzed. Patients were on PD therapy for a mean duration of 45.2 +/- 26.1 months. We found 23 episodes of PD-associated peritonitis occurred in 9 out of 27 patients (0.23 episodes/patient-year), with four patients experienced two or more peritonitis episodes. Gram-positive bacteria were responsible for 15 (65.2%) peritonitis episodes, with Staphylococcus aureus being the predominant specie isolated in 30.4% of cases. A total of seven episodes of exit-site infections (ESIs) were identified in five patients (0.069 episodes/patient-year) with the most common bacteria isolated being S. aureus (57.4%). Initial antibiotic treatment included intraperitoneal vancomycin plus ceftazidime in the majority of cases (82.6%). At the end of study, 12 (44.4%) patients remained on PD, 11 (41.8%) underwent renal transplantation, 2 (7.4%) shifted to hemodialysis and unfortunately, two patients (7.4%) died. Conclusively, our study revealed a noticeable low peritonitis and ESIs rate as compared to international data and represents the first evaluation of the characteristics and outcomes of peritonitis in the Greek pediatric PD population. PMID- 27185323 TI - Neuroimaging in encephalitis: analysis of imaging findings and interobserver agreement. AB - AIM: To assess the role of imaging in the early management of encephalitis and the agreement on findings in a well-defined cohort of suspected encephalitis cases enrolled in the Prospective Aetiological Study of Encephalitis conducted by the Health Protection Agency (now incorporated into Public Health England). MATERIALS AND METHODS: Eighty-five CT examinations from 68 patients and 101 MRI examinations from 80 patients with suspected encephalitis were independently rated by three neuroradiologists blinded to patient and clinical details. The level of agreement on the interpretation of images was measured using the kappa statistic. The sensitivity, specificity, and negative and positive predictive values of CT and MRI for herpes simplex virus (HSV) encephalitis and acute disseminated encephalomyelitis (ADEM) were estimated. RESULTS: The kappa value for interobserver agreement on rating the scans as normal or abnormal was good (0.65) for CT and moderate (0.59) for MRI. Agreement for HSV encephalitis was very good for CT (0.87) and MRI (0.82), but only fair for ADEM (0.32 CT; 0.31 MRI). Similarly, the overall sensitivity of imaging for HSV encephalitis was ~80% for both CT and MRI, whereas for ADEM it was 0% for CT and 20% for MRI. MRI specificity for HSV encephalitis between 3-10 days after symptom onset was 100%. CONCLUSION: There is a subjective component to scan interpretation that can have important implications for the clinical management of encephalitis cases. Neuroradiologists were good at diagnosing HSV encephalitis; however, agreement was worse for ADEM and other alternative aetiologies. Findings highlight the importance of a comprehensive and multidisciplinary approach to diagnosing the cause of encephalitis that takes into account individual clinical, microbiological, and radiological features of each patient. PMID- 27185326 TI - Type 1 Diabetes and Dysfunctional Intestinal Homeostasis. AB - Despite the relatively high frequency of gastrointestinal (GI) disorders in individuals with type 1 diabetes (T1D), termed diabetic enteropathy (DE), the pathogenic mechanisms of these disorders remain to be elucidated. While previous studies have assumed that DE is a manifestation of diabetic autonomic neuropathy, other contributing factors such as enteric hormones, inflammation, and microbiota were later recognized. More recently, the emerging role of intestinal stem cells (ISCs) in several GI diseases has led to a new understanding of DE. Given the absence of diagnostic methods and the lack of broadly efficacious therapeutic remedies in DE, targeting factors and pathways that control ISC homeostasis and are dysfunctional in DE may represent a new path for the detection and cure of DE. PMID- 27185325 TI - GPIHBP1 and Plasma Triglyceride Metabolism. AB - GPIHBP1, a GPI-anchored protein in capillary endothelial cells, is crucial for the lipolytic processing of triglyceride-rich lipoproteins (TRLs). GPIHBP1 shuttles lipoprotein lipase (LPL) to its site of action in the capillary lumen and is essential for the margination of TRLs along capillaries - such that lipolytic processing can proceed. GPIHBP1 also reduces the unfolding of the LPL catalytic domain, thereby stabilizing LPL catalytic activity. Many different GPIHBP1 mutations have been identified in patients with severe hypertriglyceridemia (chylomicronemia), the majority of which interfere with folding of the protein and abolish its capacity to bind and transport LPL. The discovery of GPIHBP1 has substantially revised our understanding of intravascular triglyceride metabolism but has also raised many new questions for future research. PMID- 27185327 TI - Cross-Split of Dislocations: An Athermal and Rapid Plasticity Mechanism. AB - The pathways by which dislocations, line defects within the lattice structure, overcome microstructural obstacles represent a key aspect in understanding the main mechanisms that control mechanical properties of ductile crystalline materials. While edge dislocations were believed to change their glide plane only by a slow, non-conservative, thermally activated motion, we suggest the existence of a rapid conservative athermal mechanism, by which the arrested edge dislocations split into two other edge dislocations that glide on two different crystallographic planes. This discovered mechanism, for which we coined a term "cross-split of edge dislocations", is a unique and collective phenomenon, which is triggered by an interaction with another same-sign pre-existing edge dislocation. This mechanism is demonstrated for faceted alpha-Fe nanoparticles under compression, in which we propose that cross-split of arrested edge dislocations is resulting in a strain burst. The cross-split mechanism provides an efficient pathway for edge dislocations to overcome planar obstacles. PMID- 27185328 TI - Site-Specific Characterization of Cytochrome P450cam Conformations by Infrared Spectroscopy. AB - Conformational changes are central to protein function but challenging to characterize with both high spatial and temporal precision. The inherently fast time scale and small chromophores of infrared (IR) spectroscopy are well-suited for characterization of potentially rapidly fluctuating environments, and when frequency-resolved probes are incorporated to overcome spectral congestion, enable characterization of specific sites in proteins. We selectively incorporated p-cyanophenylalanine (CNF) as a vibrational probe at five distinct locations in the enzyme cytochrome P450cam and used IR spectroscopy to characterize the environments in substrate and/or ligand complexes reflecting those in the catalytic cycle. Molecular dynamics (MD) simulations were performed to provide a structural basis for spectral interpretation. Together the experimental and simulation data suggest that the CN frequencies are sensitive to both long-range influences, resulting from the particular location of a residue within the enzyme, as well as short-range influences from hydrogen bonding and packing interactions. The IR spectra demonstrate that the environments and effects of substrate and/or ligand binding are different at each position probed and also provide evidence that a single site can experience multiple environments. This study illustrates how IR spectroscopy, when combined with the spectral decongestion and spatial selectivity afforded by CNF incorporation, provides detailed information about protein structural changes that underlie function. PMID- 27185329 TI - Design and synthesis of novel hydroxypyridinone derivatives as potential tyrosinase inhibitors. AB - Two groups of novel hydroxypyridinone derivatives 6(a-e) and 12(a-c), were designed as potential tyrosinase inhibitors, and synthesized using kojic acid as a starting material. The tyrosinase inhibitory activity of these two groups was demonstrated to be potent, especially compounds 6e and 12a, whose IC50 values for monophenolase activity were 1.95MUM and 2.79MUM, respectively. Both of these values are lower than that of kojic acid (IC50=12.50MUM). Compounds 6e and 12a were investigated for the inhibitory effect on diphenolase activity. The results showed that the inhibitory mechanism of these two compounds was reversible and that the inhibitory type was a competitive-uncompetitive mixed-type. The values of IC50 of 6e and 12a on the diphenolase activity of tyrosinase were determined to be 8.97MUM and 26.20MUM, respectively. The inhibitory constants (KI and KIS) of 6e were determined as 17.17MUM and 22.09MUM, respectively; and the KI and KIS values of 12a were 34.41MUM and 79.02MUM, respectively. Compound 6e showed a greater ability to reduce copper and a stronger copper chelating ability than kojic acid. PMID- 27185332 TI - Influence of fixation with two vs. three screws on union of arthroscopic tibio talar arthrodesis: Comparative radiographic study of 111 cases. AB - BACKGROUND: Ankle arthrodesis is a treatment of choice for advanced tibio-talar disease unresponsive to conservative treatment. Using arthroscopy to perform this procedure minimises soft-tissue trauma while providing similar outcomes to those of open surgery. Union rates have ranged across studies from 85% to 100%. The objective of this study was to assess the potential influence on union of the number of screws used for arthrodesis fixation. HYPOTHESIS: The working hypothesis was that using three screws for arthrodesis produced a higher union rate than did using only two screws. MATERIAL AND METHODS: This single-centre retrospective comparative study included 111 cases of arthroscopic ankle arthrodesis (in 108 patients) carried out between February 1994 and October 2012. The number of screws was two in 75 cases and three in 36 cases. Union was assessed on radiographs taken 2, 6, and 12months postoperatively. RESULTS: Mean age at surgery was 55.8years. After 12months, union was achieved in 87.4% cases overall. The non-union rate was 16% with two screws and 5.6% with three screws. Three-screw fixation was associated with a significantly higher rate of union of the medial gutter after 6months and of the lateral gutter after 12months. DISCUSSION: Our findings support the use of three screws for fixation of arthroscopic tibio-talar arthrodesis. Adding a third screw seems associated with a lower risk of non-union and a shorter time to union. These effects can be ascribed to greater stability of the construct. LEVEL OF EVIDENCE: Level IV, retrospective study. PMID- 27185330 TI - Discovery and optimization of a novel series of highly CNS penetrant M4 PAMs based on a 5,6-dimethyl-4-(piperidin-1-yl)thieno[2,3-d]pyrimidine core. AB - This Letter describes the chemical optimization of a novel series of M4 positive allosteric modulators (PAMs) based on a 5,6-dimethyl-4-(piperidin-1-yl)thieno[2,3 d]pyrimidine core, identified from an MLPCN functional high-throughput screen. The HTS hit was potent and selective, but not CNS penetrant. Potency was maintained, while CNS penetration was improved (rat brain:plasma Kp=0.74), within the original core after several rounds of optimization; however, the thieno[2,3 d]pyrimidine core was subject to extensive oxidative metabolism. Ultimately, we identified a 6-fluoroquinazoline core replacement that afforded good M4 PAM potency, muscarinic receptor subtype selectivity and CNS penetration (rat brain:plasma Kp>10). Moreover, this campaign provided fundamentally distinct M4 PAM chemotypes, greatly expanding the available structural diversity for this exciting CNS target. PMID- 27185331 TI - Identification, library synthesis and anti-vibriosis activity of 2-benzyl-4 chlorophenol from cultures of the marine bacterium Shewanella halifaxensis. AB - Summer Gut Syndrome (SGS) is caused by various Vibrio bacterial species and can have negative effects on aquaculture farms worldwide. In New Zealand, SGS is caused by Vibrio harveyii infecting King Salmon (Oncorhynchus tshawytscha). To find leads for the prevention of SGS, we screened the inhibitory effects of 16 strains of Shewanella upon V. harveyii growth in competitive solid phase cultures. The detailed investigation of Shewanella halifaxensis IRL548 revealed 2 benzyl-4-chlorophenol (1), a known, commercially available antibacterial agent, as the major bioactive component. Synthesis of a small library of congeners to confirm the natural product identity and to provide a structure-activity relationship for the observed activity was also completed. Compound 1 exhibits moderate activity against two pathogenic microorganisms. PMID- 27185334 TI - Omic Relief for the Biotically Stressed: Metabolomics of Plant Biotic Interactions. AB - Many aspects of the way plants protect themselves against pathogen attack, or react upon such an attack, are realized by metabolites. The ambitious aim of metabolomics, namely the identification and annotation of the entire cellular metabolome, still poses a considerable challenge due to the high diversity of the metabolites in the cell. Recent advances in analytical methods and data analysis have resulted in improved sensitivity, accuracy, and capacity, allowing the analysis of several hundreds or even thousands of compounds within one sample. Investigators have only recently begun to acknowledge and harness the power of metabolomics to elucidate key questions in the study of plant biotic interactions; we review trends and developments in the field. PMID- 27185333 TI - GR gene polymorphism is associated with inter-subject variability in response to glucocorticoids in patients with myasthenia gravis. AB - BACKGROUND AND PURPOSE: Glucocorticoids (GCs) are the mainstay treatment of myasthenia gravis (MG). However, wide inter-individual variability exists in the response to GCs. METHODS: A Chinese cohort of 257 MG patients treated with GCs was evaluated for the association between 19 single nucleotide polymorphisms in the GR gene and clinical response to the initial 3 month GC therapy. A quantitative MG score decreasing by >=3 units or becoming zero was defined as sensitivity to GCs. RESULTS: The rs17209237* G allele was less frequent in the GC insensitive group compared with the GC sensitive group [P = 0.013, odds ratio (OR) 0.119]. The rs9324921* A allele was more frequent in the GC insensitive group than in the GC sensitive group (P = 0.046, OR 1.94). Carriers of the rs17209237 G allele were less frequent in the GC insensitive group than in the GC sensitive group (dominant model, P = 0.009). Carriers of the rs9324921 A allele were more frequent in the GC insensitive group than in the GC sensitive group (dominant model, P = 0.037). Multivariate logistic regression revealed that the rs17209237 G allele carrier (P = 0.037, OR 0.12) and disease duration before GC treatment (P = 0.011, OR 3.45) were independent factors that contributed to GC efficacy. CONCLUSION: rs17209237 in the GR gene was identified as an independent factor that contributes to GC efficacy in MG patients. The genetic variations of the GR gene may play a role in predicting response to GC treatment. PMID- 27185335 TI - Structural characterization and bioactivity of proanthocyanidins from indigenous cinnamon (Cinnamomum osmophloeum). AB - BACKGROUND: Barks and twigs of common species of cinnamon with abundant proanthocyanidins are used as a spice, fold medicine or supplement. Cinnamomum osmophloeum is an endemic species in Taiwan and coumarin was not detected in the oil of the C. osmophloeum twig. The present study aimed to evaluate the relationship between the bioactivities and proanthocyanidins of C. osmophloeum twig extracts (CoTE). The n-butanol soluble fraction from CoTE was divided into 10 subfractions (F1-F10) by Sephadex LH-20 gel chromatography. The antihyperglycemic activities were examined by alpha-glucosidase, alpha-amylase and protein tyrosine phosphatase 1B inhibitory assays. Total antioxidant activities were examined by 2,2-diphenyl-1-picrylhydrazyl free radical scavenging and ferrous ion-chelating assays. RESULTS: The results revealed that subfractions F6-F10, with high proanthocyanidin contents, showed excellent antihyperglycemic and antioxidant activities. Subfractions F6-F10 were analyzed further by matrix assisted laser desorption/ionization-time of flight/mass spectrometry and thiolysis-reversed-phase high-performance liquid chromatography/tandem mass spectrometry methods. The results showed that the mean degrees of polymerization of proanthocyanidins in subfractions F6-F10 ranged from 3.5 to 5.1, with the highest degrees of polymerization of proanthocyanidins reaching 8 in subfractions F8-F10. Two compounds in F6 were identified as cinnamtannin B1 and parameritannin A1. These proanthocyanidins contained at least one A-type and major B-type linkages. CONCLUSION: These results demonstrate that proanthocyanidins are associated with their antihyperglycemic and antioxidant activities in CoTE. (c) 2016 Society of Chemical Industry. PMID- 27185336 TI - pH and antioxidant measurements in rats with testicular torsion and their correlation with viability. PMID- 27185337 TI - Major penile injuries as a result of cautery during newborn circumcision. AB - AIM: To report a grading system for complications of male circumcision, and to represent our experience with salvage surgery for postcircumcision electro cautery penile ablation injuries. PATIENTS AND METHODS: Circumcision injuries presented to our department between January 2010 and January 2015 were collected and graded into five categories according to the degree of penile injury, and the possibility for surgical reversibility. RESULTS: Salvage surgery was carried out on 5 cases of post circumcision total phallic loss (grade V injuries). One of the cases had a postoperative meatal stenosis that responded to dilation under general anesthesia. No skin graft problems were documented in the other cases. The cosmetic outlook was greatly appreciated by the family and the operating team at follow up of all cases. CONCLUSION: Grading the post circumcision penile injuries is of paramount importance, and reconstructing the phallus using the hidden corporal bodies is considered worthwhile. PMID- 27185339 TI - The Spectrum of Mild to Severe Psoriasis Vulgaris Is Defined by a Common Activation of IL-17 Pathway Genes, but with Key Differences in Immune Regulatory Genes. AB - Mild versus severe psoriasis is often distinguished by clinical measures such as the extent of skin involvement or Psoriasis Area and Severity Index score, both of which use arbitrary boundaries. It is widely assumed that severe psoriasis involves higher levels of skin inflammation, but comparative molecular profiles of mild versus severe disease have not been performed. In this study, we used immunohistochemistry, reverse transcription PCR, and gene arrays to determine the phenotype of North American patients with mild psoriasis (n = 34, mean PASI score = 5.5) versus severe psoriasis (n = 23, mean PASI score = 23.2). Overall, skin inflammation, defined as the sum of T-cell infiltration/activation and IL-17 mediated epidermal responses, was not higher in severe psoriasis lesions. Surprisingly, mild psoriasis was characterized by higher numbers of T cells in skin lesions, higher IL-17A expression, and stronger expression of the core psoriasis transcriptome. In contrast, severe psoriasis was characterized by stronger expression of some epidermal response genes (TGFA, CALM1, SMPD3, and IL1RL2). However, a key molecular distinction was higher expression of negative immune regulatory genes (CTLA4, CD69 and PD-L1) in mild lesions compared with severe psoriasis lesions. These data have important implications for treating psoriasis across the spectrum of disease, as well as for potential mechanisms that allow psoriasis to progress to more extensive cutaneous disease. PMID- 27185338 TI - Dibutyltin-induced alterations of interleukin 1beta secretion from human immune cells. AB - Dibutyltin (DBT) is used to stabilize polyvinyl chloride plastics (including pipes that distribute drinking water) and as a de-worming agent in poultry. DBT is found in human blood, and DBT exposures alter the secretion of tumor necrosis factor alpha and interferon gamma from lymphocytes. Interleukin (IL)-1beta is a proinflammatory cytokine that regulates cellular growth, tissue restoration and immune response regulation. IL-1beta plays a role in increasing invasiveness of certain tumors. This study reveals that exposures to DBT (24 h, 48 h and 6 days) modify the secretion of IL-1beta from increasingly reconstituted preparations of human immune cells (highly enriched human natural killer cells, monocyte-depleted [MD] peripheral blood mononuclear cells [PBMCs], PBMCs, granulocytes and a preparation combining both PBMCs and granulocytes). DBT altered IL-1beta secretion from all cell preparations. Higher concentrations of DBT (5 and 2.5 MUm) decreased the secretion of IL-1beta, while lower concentrations of DBT (0.1 and 0.05 MUm) increased the secretion of IL-1beta. Selected signaling pathways were examined in MD-PBMCs to determine if they play a role in DBT-induced elevations of IL-1beta secretion. Pathways examined were IL-1beta converting enzyme (caspase 1), mitogen-activated protein kinases and nuclear factor kappa B. Caspase 1 and mitogen-activated protein kinase pathways appear to be utilized by DBT in increasing IL-1beta secretion. These results indicate that DBT alters IL 1beta secretion from human immune cells in an ex. vivo system utilizing several IL-1beta regulating signaling pathways. Thus, DBT may have the potential to alter IL-1beta secretion in an in vivo system. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27185340 TI - UVA-Irradiation Induces Melanoma Invasion via the Enhanced Warburg Effect. AB - Melanoma is a malignant tumor in which UVA (320-400 nm) radiation is considered to be an important risk factor. But the role of UVA in melanoma progression toward an invasive phenotype is still not adequately investigated. For most proliferating tumor cells the preference of aerobic glycolysis has been described as the Warburg effect. Here we investigate the effect of UVA irradiation on changes in the Warburg effect and tumor progression toward invasive potential. On UVA irradiation, melanoma cell lines from initial tumors show an induction of the Warburg effect with increased glucose consumption and lactate production, which is at least partially mediated by reactive oxygen species. Associated with UVA treatment and enhanced lactic acid production, tumor-relevant proteases and in situ invasion is upregulated. Simultaneously, UVA increases intracellular concentrations of progression marker transketolase and activated protein kinase Akt, both involved in metabolic changes that increase with proliferation. Using invasion assays we show that lactic acid, resulting from the UVA enhanced and partially reactive oxygen species-mediated Warburg effect, increases the invasive potential of all melanoma cell lines investigated. Therefore, we demonstrate in melanoma cells that production of lactic acid, induced by UVA irradiation, increases invasiveness of melanoma cells via expression of tumor-relevant proteases. PMID- 27185341 TI - Analysis of the glutathione S-transferase genes polymorphisms in the risk and prognosis of renal cell carcinomas. Case-control and meta-analysis. AB - BACKGROUND: The Glutathione S-transferases (GSTs) genes deletion polymorphisms have been associated with the progression of several cancers. The association studies between the 2 GSTs (GSTM1 and GSTT1) null polymorphisms with the susceptibility to renal cell carcinoma (RCC) have been inconclusive. Therefore, with the inclusion of our own data, we performed a comprehensive meta-analysis to assess the association between these 2 polymorphisms and the risk of RCC. METHODS: A systematic literature search was carried out for studies published in the PubMed, EMBASE, Cochrane library, and Google Scholar from 1997 to December 2014. Results were stated as pooled odds ratios (ORs) for nonparametric data after heterogeneity analysis with 95% CI using fixed effect or random effect model. RESULTS: We systematically selected 13 relevant studies after thorough searches from the databases. Data showed no association between the GSTM1 and the GSTT1 null genotypes and the risk of RCC (OR = 1.01; CI: 0.92-1.11; P = 0.89 for GSTM1 and OR = 1.14; CI: 0.91-1.42; P = 0.25 for GSTT1). No association was found when the data were stratified according to the geographical/ethnic basis, source of control, and the risk factor evaluation. Subgroup analysis of occupational exposure to pesticides showed an inverse association of the active genotypes of both GSTM1 and GSTT1 polymorphisms with the exposed group of RCC (P<0.00001 and P<0.00001, respectively). The combined null genotype of the GSTM1/GSTT1 significantly increased the susceptibility to RCC by 1.4-fold (P = 0.001). This association remained significant for the Asian populations in subgroup analysis (OR = 1.8; CI: 1.30-2.49; P = 0.0004). CONCLUSION: In conclusion, this meta analysis suggests that the 2 GSTs deletion polymorphisms independently have no association with the risk of RCC. However, combination of both deletions increases the risk of developing the RCC. PMID- 27185343 TI - Uniaxial ferroelectric quantum criticality in multiferroic hexaferrites BaFe12O19 and SrFe12O19. AB - BaFe12O19 is a popular M-type hexaferrite with a Neel temperature of 720 K and is of enormous commercial value ($3 billion/year). It is an incipient ferroelectric with an expected ferroelectric phase transition extrapolated to lie at 6 K but suppressed due to quantum fluctuations. The theory of quantum criticality for such uniaxial ferroelectrics predicts that the temperature dependence of the electric susceptibility chi diverges as 1/T(3), in contrast to the 1/T(2) dependence found in pseudo-cubic materials such as SrTiO3 or KTaO3. In this paper we present evidence of the susceptibility varying as 1/T(3), i.e. with a critical exponent gamma = 3. In general gamma = (d + z - 2)/z, where the dynamical exponent for a ferroelectric z = 1 and the dimension is increased by 1 from deff = 3 + z to deff = 4 + z due to the effect of long-range dipole interactions in uniaxial as opposed to multiaxial ferroelectrics. The electric susceptibility of the incipient ferroelectric SrFe12O19, which is slightly further from the quantum phase transition is also found to vary as 1/T(3). PMID- 27185342 TI - Development and external multicenter validation of Chinese Prostate Cancer Consortium prostate cancer risk calculator for initial prostate biopsy. AB - OBJECTIVE: Substantial differences exist in the relationship of prostate cancer (PCa) detection rate and prostate-specific antigen (PSA) level between Western and Asian populations. Classic Western risk calculators, European Randomized Study for Screening of Prostate Cancer Risk Calculator, and Prostate Cancer Prevention Trial Risk Calculator, were shown to be not applicable in Asian populations. We aimed to develop and validate a risk calculator for predicting the probability of PCa and high-grade PCa (defined as Gleason Score sum 7 or higher) at initial prostate biopsy in Chinese men. MATERIALS AND METHODS: Urology outpatients who underwent initial prostate biopsy according to the inclusion criteria were included. The multivariate logistic regression-based Chinese Prostate Cancer Consortium Risk Calculator (CPCC-RC) was constructed with cases from 2 hospitals in Shanghai. Discriminative ability, calibration and decision curve analysis were externally validated in 3 CPCC member hospitals. RESULTS: Of the 1,835 patients involved, PCa was identified in 338/924 (36.6%) and 294/911 (32.3%) men in the development and validation cohort, respectively. Multivariate logistic regression analyses showed that 5 predictors (age, logPSA, logPV, free PSA ratio, and digital rectal examination) were associated with PCa (Model 1) or high-grade PCa (Model 2), respectively. The area under the curve of Model 1 and Model 2 was 0.801 (95% CI: 0.771-0.831) and 0.826 (95% CI: 0.796-0.857), respectively. Both models illustrated good calibration and substantial improvement in decision curve analyses than any single predictors at all threshold probabilities. Higher predicting accuracy, better calibration, and greater clinical benefit were achieved by CPCC-RC, compared with European Randomized Study for Screening of Prostate Cancer Risk Calculator and Prostate Cancer Prevention Trial Risk Calculator in predicting PCa. CONCLUSIONS: CPCC-RC performed well in discrimination and calibration and decision curve analysis in external validation compared with Western risk calculators. CPCC-RC may aid in decision-making of prostate biopsy in Chinese or in other Asian populations with similar genetic and environmental backgrounds. PMID- 27185344 TI - High-Resolution Vertical Observation of Intracellular Structure Using Magnetically Responsive Microplates. AB - A vertical confocal observation system capable of high-resolution observation of intracellular structure is demonstrated. The system consists of magnet-active microplates to rotate, incline, and translate single adherent cells in the applied magnetic field. Appended to conventional confocal microscopes, this system enables high-resolution cross-sectional imaging with single-molecule sensitivity in single scanning. PMID- 27185345 TI - Nucleation and growth of (10?11) semi-polar AlN on (0001) AlN by Hydride Vapor Phase Epitaxy. AB - Wurtzite AlN is widely used for deep ultraviolet optoelectronic devices (DUV), which are generally grown along the [0001]-direction of the wurtzite structure on currently available substrates. However, huge internal electrostatic fields are presented within the material along [0001] axis induced by piezoelectric and spontaneous polarization, which has limited the internal quantum efficiency of AlN based DUV LEDs dramatically. The internal fields can be strongly reduced by changing the epitaxial growth direction from the conventional polar c-direction into less polar crystal directions. Twinned crystal is a crystal consisting of two or more domains with the same crystal lattice and composition but different crystal orientations. In other words, twins can be induced to change crystal directions. In this work we demonstrated that the epitaxial growth of () semi polar AlN on (0001) AlN by constructing () and () twin structures. This new method is relative feasible than conventional methods and it has huge prospect to develop high-quality semi-polar AlN. PMID- 27185346 TI - Responses of soil buffering capacity to acid treatment in three typical subtropical forests. AB - Elevated anthropogenic acid deposition can significantly affect forest ecosystem functioning by changing soil pH, nutrient balance, and chemical leaching and so on. These effects generally differ among different forests, and the dominant mechanisms for those observed responses often vary, depending on climate, soil conditions and vegetation types. Using soil monoliths (0-40cm) from pine forest (pioneer), coniferous and broadleaved mixed forest (transitional) and broadleaved forest (mature) in southern China, we conducted a leaching experiment with acid treatments at different pH levels (control: pH~4.5; pH=3.5; pH=2.5). We found that pH3.5 treatment significantly reduced dissolved organic carbon (DOC) concentrations in leachate from the pioneer forest soil. pH2.5 treatment significantly increased concentrations of NO3(-), SO4(2-), Ca(2+), Mg(2+), Al(3+), Fe(3+) and DOC in leachate from the pioneer forest soil, and also concentrations of NO3(-), SO4(2-), Mg(2+), Al(3+), Fe(3+) and DOC in leachate from the transitional forest soil. All acid treatments had no significant effects on concentrations of these chemicals in leachate from the mature forest soil. The responses can be explained by the changes in soil pH, acid neutralizing capacity (ANC) and concentrations of Al and Fe. Our results showed that acid buffering capacity of the pioneer or transitional forest soil was lower than that of the mature forest soil. Therefore preserving mature forests in southern China is important for reducing the adverse impacts of high acid deposition on stream water quality at present and into the future. PMID- 27185347 TI - Post fire organic matter biodegradation in permafrost soils: Case study after experimental heating of mineral horizons. AB - Periodical ground fires of high frequency in permafrost forest ecosystems of Siberia (Russian Federation) are essential factors determining quantitative and qualitative parameters of permafrost soil organic matter. Specific changes in physical and chemical parameters and microbial activity of permafrost soil mineral horizons of northern taiga larch stands were revealed after heating at high temperatures (150-500 degrees C) used for imitation of different burn intensities. Burning at 150-200 degrees C resulted in decreasing of soil pH, whilst heating at 300-500 degrees C caused increase of pH compare to unheated soils. Water-soluble organic carbon concentration in permafrost soils heated at 150-200 degrees C was much higher than that of unheated soils. All these changes determined soil microbial activity in heated soils. In particular, in soils heated at 300-500 degrees C there was momentary stimulating effect on substrate induced respiration registered and on basal respiration values in soils burned at 150 degrees C and 300-400 degrees C. Four-month laboratory incubation of permafrost soils heated at different temperatures showed stimulation of microbial activity in first several days after inoculation due to high substrate availability after heating. Then soon after that soil microbial community started to be depleted on substrate because of decreasing water-soluble organic carbon, C and N content and it continued to the end of incubation. PMID- 27185349 TI - Decadal-scale export of nitrogen, phosphorus, and sediment from the Susquehanna River basin, USA: Analysis and synthesis of temporal and spatial patterns. AB - The export of nitrogen (N), phosphorus (P), and suspended sediment (SS) is a long standing management concern for the Chesapeake Bay watershed, USA. Here we present a comprehensive evaluation of nutrient and sediment loads over the last three decades at multiple locations in the Susquehanna River basin (SRB), Chesapeake's largest tributary watershed. Sediment and nutrient riverine loadings, including both dissolved and particulate fractions, have generally declined at all sites upstream of Conowingo Dam (non-tidal SRB outlet). Period-of record declines in riverine yield are generally smaller than those in source input, suggesting the possibility of legacy contributions. Consistent with other watershed studies, these results reinforce the importance of considering lag time between the implementation of management actions and achievement of river quality improvement. Whereas flow-normalized loadings for particulate species have increased recently below Conowingo Reservoir, those for upstream sites have declined, thus substantiating conclusions from prior studies about decreased reservoir trapping efficiency. In regard to streamflow effects, statistically significant log-linear relationships between annual streamflow and annual constituent load suggest the dominance of hydrological control on the inter annual variability of constituent export. Concentration-discharge relationships revealed general chemostasis and mobilization effects for dissolved and particulate species, respectively, both suggesting transport-limitation conditions. In addition to affecting annual export rates, streamflow has also modulated the relative importance of dissolved and particulate fractions, as reflected by its negative correlations with dissolved P/total P, dissolved N/total N, particulate P/SS, and total N/total P ratios. For land-use effects, period-of-record median annual yields of N, P, and SS all correlate positively with the area fraction of non-forested land but negatively with that of forested land under all hydrological conditions. Overall, this work has informed understanding with respect to four major factors affecting constituent export (i.e., source input, reservoir modulation, streamflow, and land use) and demonstrated the value of long-term river monitoring. PMID- 27185348 TI - Estimating the effects of land use at different scales on high ecological status in Irish rivers. AB - High ecological status at river sites is an indicator of minimal disturbance from anthropogenic activities and the presence of ecologically important species and communities. However, a lack of clarity on what factors cause sites to lose high ecological status is limiting the ability to maintain the quality of these sites. Examination of ecological status records at 508 high status river sites throughout the Republic of Ireland revealed that 337 had fallen below high status at some point between 2001 and 2012 due to changes in invertebrate communities. A geographical information system was used to characterise land use and environmental variables in the catchment, riparian and reach areas upstream of the sites. The relationships between these variables at the three spatial scales and whether or not river sites had maintained high ecological status were then estimated by multiple logistic regression and propensity modelling. The results indicated that grassland at either catchment or riparian scales had a greater negative impact on high ecological status than at the reach scale. This effect appeared to be strongest for upland, steeply sloping rivers that are subject to high rainfall, possibly due to the presence of sensitive biota and/or a greater potential for erosion. These results highlighted the need for better management of grassland upstream of the high status sites, with a focus on river alterations and critical source areas of nutrients, sediments and pesticides that are hydrologically connected to the river. Sustainable management practices and land use planning in those areas will need to be considered carefully if the aim of maintaining high ecological status at river sites is to be achieved. PMID- 27185350 TI - The copper spoil heap Knappenberg, Austria, as a model for metal habitats - Vegetation, substrate and contamination. AB - Historic mining in the Eastern Alps has left us with a legacy of numerous spoil heaps hosting specific, metal tolerant vegetation. Such habitats are characterized by elevated concentrations of toxic elements but also by high irradiation, a poorly developed substrate or extreme pH of the soil. This study investigates the distribution of vascular plants, mosses and lichens on a copper spoil heap on the ore bearing Knappenberg formed by Prebichl Layers and Werfener Schist in Lower Austria. It serves as a model for discriminating between various ecological traits and their effects on vegetation. Five distinct clusters were distinguished: (1) The bare, metal rich Central Spoil Heap was only colonised by highly resistant specialists. (2) The Northern and (3) Southern Peripheries contained less copper; the contrasting vegetation was best explained by the different microclimate. (4) A forest over acidic bedrock hosted a vegetation overlapping with the periphery of the spoil heap. (5) A forest over calcareous bedrock was similar to the spoil heap with regard to pH and humus content but hosted a vegetation differing strongly to all other habitats. Among the multiple toxic elements at the spoil heap, only Cu seems to exert a crucial influence on the vegetation pattern. Besides metal concentrations, irradiation, humidity, humus, pH and grain size distribution are important for the establishment of a metal tolerant vegetation. The difference between the species poor Northern and the diverse Southern Periphery can be explained by the microclimate rather than by the substrate. All plant species penetrating from the forest into the periphery of the spoil heap originate from the acidic but not from the calcareous bedrock. PMID- 27185351 TI - ADAM12-deficient zebrafish exhibit retardation in body growth at the juvenile stage without developmental defects. AB - ADAM (a disintegrin and metalloprotease) constitutes a family of multi-domain proteins that are involved in development, homeostasis, and disease. ADAM12 plays important roles in myogenesis and adipogenesis in mice; however, the precise physiological mechanisms are not known, and the function of this gene in other vertebrates has not been examined. In this study, we used a simple model vertebrate, the zebrafish, to investigate the functions of ADAM12 during development. Zebrafish adam12 is conserved with those of mammals in the synteny and the amino-acid sequence. We examined adam12 expression in zebrafish embryos by whole mount in situ hybridization and the promoter activity of the adam12 upstream sequence. We found that adam12 is strongly expressed in the cardiovascular system, erythroid progenitors, brain, and jaw cartilage during zebrafish development, and adam12-knockout zebrafish exhibited reduced body size in the juvenile stage without apparent morphological defects. Taken together, these results suggest that adam12 plays a significant role in the regulation of body growth during juvenile stage in zebrafish, although the precise molecular mechanisms await further study. PMID- 27185352 TI - Detection of one-dimensional migration of single self-interstitial atoms in tungsten using high-voltage electron microscopy. AB - The dynamic behaviour of atomic-size disarrangements of atoms-point defects (self interstitial atoms (SIAs) and vacancies)-often governs the macroscopic properties of crystalline materials. However, the dynamics of SIAs have not been fully uncovered because of their rapid migration. Using a combination of high-voltage transmission electron microscopy and exhaustive kinetic Monte Carlo simulations, we determine the dynamics of the rapidly migrating SIAs from the formation process of the nanoscale SIA clusters in tungsten as a typical body-centred cubic (BCC) structure metal under the constant-rate production of both types of point defects with high-energy electron irradiation, which must reflect the dynamics of individual SIAs. We reveal that the migration dimension of SIAs is not three dimensional (3D) but one-dimensional (1D). This result overturns the long standing and well-accepted view of SIAs in BCC metals and supports recent results obtained by ab-initio simulations. The SIA dynamics clarified here will be one of the key factors to accurately predict the lifetimes of nuclear fission and fusion materials. PMID- 27185353 TI - Familial hypercholesterolaemia: beware of lipoprotein(a). PMID- 27185355 TI - Antibiotic resistance profiles of coagulase-negative staphylococci in livestock environments. AB - Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) have globally emerged in animal husbandry. In addition to methicillin resistance, LA MRSA may carry a variety of novel and uncommon antimicrobial resistance genes. Occurrence of the same resistance genes in coagulase-negative staphylococci (CoNS) and S. aureus suggests an ongoing genetic exchange between LA-MRSA and other staphylococci whose driving forces in the ecological niche of the farm environment are, however, still poorly understood. To assess the potential of CoNS as putative reservoirs for antibiotic resistance genes, we analysed the antimicrobial susceptibility of CoNS from dust and manure samples obtained in 41 pig farms in Germany, most of them (36 of 41) with a proven LA-MRSA/MSSA history. Among the 344 isolates analysed, 18 different CoNS species were identified and S. sciuri represented the most prevalent species (46%). High resistance rates were detected for tetracycline (71%), penicillin (65%) and oxacillin (64%) as well as fusidic acid (50%), which was mainly due to reduced susceptibility among S. sciuri isolates. S. sciuri exhibited pronounced multiresistance, and many isolates were characterised by the carriage of a number of uncommon (multi)resistance genes (e.g. cfr, apmA, fexA) and decreased susceptibility towards last resort antibiotics such as linezolid and daptomycin. The combined data suggest that S. sciuri harbours a significant resistance gene pool that requires further attention. We hypothesise that members of this species, due to their flexible lifestyle, might contribute to the spread of such genes in livestock environments. PMID- 27185354 TI - High lipoprotein(a) as a possible cause of clinical familial hypercholesterolaemia: a prospective cohort study. AB - BACKGROUND: The reason why lipoprotein(a) concentrations are raised in individuals with clinical familial hypercholesterolaemia is unclear. We tested the hypotheses that high lipoprotein(a) cholesterol and LPA risk genotypes are a possible cause of clinical familial hypercholesterolaemia, and that individuals with both high lipoprotein(a) concentrations and clinical familial hypercholesterolaemia have the highest risk of myocardial infarction. METHODS: We did a prospective cohort study that included data from 46 200 individuals from the Copenhagen General Population Study who had lipoprotein(a) measurements and were genotyped for common familial hypercholesterolaemia mutations. Individuals receiving cholesterol-lowering drugs had their concentrations of LDL and total cholesterol multiplied by 1.43, corresponding to an estimated 30% reduction in LDL cholesterol from the treatment. In lipoprotein(a) cholesterol-adjusted analyses, total cholesterol and LDL cholesterol were adjusted for the lipoprotein(a) cholesterol content by subtracting 30% of the individuals' lipoprotein(a) total mass before total and LDL cholesterol were used for diagnosis of clinical familial hypercholesterolaemia. We used modified Dutch Lipid Clinic Network (DLCN), Simon Broome, and Make Early Diagnosis to Prevent Early Death (MEDPED) criteria to clinically diagnose familial hypercholesterolaemia. Cox proportional hazard regression calculated hazard ratios (95% CI) of myocardial infarction. FINDINGS: Using unadjusted LDL cholesterol, mean lipoprotein(a) concentrations were 23 mg/dL in individuals unlikely to have familial hypercholesterolaemia, 32 mg/dL in those with possible familial hypercholesterolaemia, and 35 mg/dL in those with probable or definite familial hypercholesterolaemia (ptrend<0.0001). However, when adjusting LDL cholesterol for lipoprotein(a) cholesterol content the corresponding values were 24 mg/dL for individuals unlikely to have familial hypercholesterolaemia, 22 mg/dL for those with possible familial hypercholesterolaemia, and 21 mg/dL for those with probable or definite familial hypercholesterolaemia (ptrend=0.46). High lipoprotein(a) cholesterol accounted for a quarter of all individuals diagnosed with clinical familial hypercholesterolaemia and LPA risk genotypes were more frequent in clinical familial hypercholesterolaemia, whereas lipoprotein(a) concentrations were similar in those with and without familial hypercholesterolaemia mutations. The hazard ratios (HRs) for myocardial infarction compared with individuals unlikely to have familial hypercholesterolaemia and lipoprotein(a) concentration of 50 mg/dL or less were 1.4 (95% CI 1.1-1.7) in those unlikely to have familial hypercholesterolaemia and lipoprotein(a) concentrations of more than 50 mg/dL, 3.2 (2.5-4.1) in those with possible, probable, or definite familial hypercholesterolaemia and lipoprotein(a) concentration of 50 mg/dL or less, and 5.3 (3.6-7.6) in those with possible, probable, or definite familial hypercholesterolaemia and lipoprotein(a) concentration of more than 50 mg/dL. In analyses using Simon Broome or MEDPED criteria, results were similar to those using DLCN criteria to diagnose clinical familial hypercholesterolaemia. INTERPRETATION: High lipoprotein(a) concentrations and corresponding LPA risk genotypes represent novel risk factors for clinical familial hypercholesterolaemia. Our findings suggest that all individuals with familial hypercholesterolaemia should have their lipoprotein(a) measured in order to identify those with the highest concentrations, and as a result, the highest risk of myocardial infarction. FUNDING: Danish Heart Association and IMK General Fund, Denmark. PMID- 27185356 TI - Luteolin protects the hippocampus against neuron impairments induced by kainic acid in rats. AB - Glutamatergic excitotoxicity is crucial in the pathogenesis of numerous brain disorders. Luteolin, a flavonoid compound, inhibits glutamate release, however, its ability to affect glutamate-induced brain injury is unknown. Therefore, this study evaluated the protective effect of luteolin against brain damage induced by kainic acid (KA), a glutamate analog. Rats were treated with luteolin (10 or 50mg/kg, intraperitoneally) 30min before an intraperitoneal injection of KA (15mg/kg). Luteolin treatment reduced the KA-induced seizure score and elevations of glutamate levels in the hippocampus. A histopathological analysis showed that luteolin attenuated KA-induced neuronal death and microglial activation in the hippocampus. An immunoblotting analysis showed that luteolin restored the KA induced reduction in Akt phosphorylation in the hippocampus. Furthermore, a Morris water maze test revealed that luteolin effectively prevented KA-induced learning and memory impairments. The results suggest that luteolin protected rat brains from KA-induced excitotoxic damage by reducing glutamate levels, mitigating inflammation, and enhancing Akt activation in the hippocampus. Therefore, luteolin may be beneficial for preventing or treating brain disorders associated with excitotoxic neuronal damage. PMID- 27185357 TI - LC3-associated phagocytosis: a crucial mechanism for antifungal host defence against Aspergillus fumigatus. AB - LC3-associated phagocytosis (LAP) is a non-canonical autophagy pathway involved in the maturation of single-membrane phagosomes and subsequent killing of ingested pathogens by phagocytes. This pathway is initiated following recognition of pathogens by pattern recognition receptors and leads to the recruitment of LC3 into the phagosomal membrane. This form of phagocytosis is utilized for the antifungal host defence and is required for an efficient fungal killing. Here, we provide an overview of the LAP pathway and review the role of LAP in anti Aspergillus host defence, as well as mechanisms induced by Aspergillus that modulate LAP to promote its survival in the host. PMID- 27185358 TI - Measuring spleen stiffness to predict varices in chronic hepatitis B cirrhotic patients with or without receiving non-selective beta-blockers. AB - OBJECTIVES: we aimed to investigate the accuracy of liver (LSM) spleen stiffness measurement (SSM) with transient elastography (TE) to predict varices in the presence of non-selective beta-blockers (NSBB). METHODS: In this cross-sectional study of consecutive patients with chronic hepatitis B (CHB) and cirrhosis, all patients underwent TE and upper endoscopic examinations. LSM and SSM in predicting varices in patients receiving and not receiving NSBB were evaluated. RESULTS: Altogether 144 CHB patients (29 receiving NSBB; 35 with any varices, 31 and 11 with esophageal and gastric varices, respectively) were recruited. Their mean LSM and SSM were 13.3 +/- 9.0 kPa and 32.8 +/- 19.2 kPa, respectively. The correlation between LSM and SSM was better in the NSBB subgroup (r = 0.525, P = 0.003) than its counterpart (r = 0.329, P < 0.001). The area under receiver operating characteristic curve (AUROC) of LSM and SSM for any varices was 0.675 and 0.685 (P = 0.002 and 0.001), respectively. SSM of 18.9 kPa had a negative predictive value of 92.1% and negative likelihood ratio of 0.27 for ruling out any varices; and SSM of 54.9 kPa had a positive predictive value of 56.5% and a positive likelihood ratio of 4.05 to rule in varices. The AUROC of LSM for varices was 0.742 and 0.549 in patients with or without NSBB, respectively; the corresponding AUROC of SSM was 0.572 and 0.603, respectively. CONCLUSIONS: SSM only has modest accuracy to predict varices independent of NSBB use. An SSM cutoff value of 18.9 kPa may be adopted to achieve a high negative predictive value to rule out varices. PMID- 27185359 TI - Cryoprecipitate indications and patterns of use in the pediatric intensive care unit: inappropriate transfusions and lack of standardization. AB - BACKGROUND: The dosage and indications for cryoprecipitate are not well studied for any patient population. Prior observational studies have suggested that 24% to 62% of cryoprecipitate transfusions are inappropriate, and there is limited information on patterns of cryoprecipitate use in children. The purpose of this retrospective study was to explore the indications and appropriateness of the use of cryoprecipitate in critically ill children. STUDY DESIGN AND METHODS: We retrospectively reviewed the electronic medical records for cryoprecipitate ordering and utilization in the pediatric intensive care unit at a large tertiary care center during a 4.5-year period. RESULTS: For the 44 patients receiving cryoprecipitate, the only indication was for fibrinogen replacement and the most common clinical scenarios were recent cardiac surgery (39%) and disseminated intravascular coagulation in the setting of sepsis (32%). Cryoprecipitate was often transfused empirically at higher-than-recommended doses without a known pretransfusion fibrinogen level, and the majority (61%) of cryoprecipitate transfusions were deemed inappropriate according to our institutional guidelines. The indications selected for cryoprecipitate by providers during physician order entry matched the clinical scenario, assessed by chart and laboratory data review, in only 18% of patients. There was no significant difference in red blood cell usage in the 6-hour windows before and after cryoprecipitate transfusion. CONCLUSION: Our study demonstrates a lack of standardization for the use of cryoprecipitate in critically ill children, including many inappropriate transfusions at higher-than-recommended dosing. Prospective randomized clinical trials are warranted to help determine appropriate indications and efficacious cryoprecipitate dosing in the pediatric population. PMID- 27185360 TI - Professor Lynn Myers 13th June 1954 - 21st August 2015. PMID- 27185361 TI - Psychological Vulnerability and Subjective Happiness: The Mediating Role of Hopelessness. AB - The current study examined the mediating role of hopelessness on the relationship between psychological vulnerability and subjective happiness. It was anticipated that hopelessness may act as a mediator in the relationship between psychological vulnerability and subjective happiness. Two hundred sixty-nine (150 women and 119 men) university students completed the Psychological Vulnerability Scale, the Subjective Happiness Scale and the Beck Hopelessness Scale. Data have been collected in the 2013-2014 academic year. The present study was designed as a cross-sectional study. Correlational results indicated that psychological vulnerability and hopelessness were significantly negatively associated with subjective happiness. Results using structural equation modelling showed that hopelessness fully mediated the relationship between psychological vulnerability and subjective happiness. Implications for future research and limitations of the present study are discussed. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27185362 TI - Determination of hemispheric language dominance using functional magnetic resonance imaging and the Shiritori (Japanese word chain) task in patients with epilepsy: Comparison with the Wada test. AB - PURPOSE: The Wada test has been the gold standard for determining hemispheric language dominance (HLD) in the presurgical evaluation of patients scheduled for neurosurgical procedures. As it poses inherent risks associated with intra arterial catheter techniques and as it occasionally fails to indicate language dominance, an alternative reliable test is needed. We quantitatively assessed the results of functional magnetic resonance imaging (fMRI) using the Shiritori task, a Japanese word chain, to identify the threshold for correctly predicting HLD. METHODS: The subjects were 28 patients with intractable epilepsy scheduled to undergo the Wada test and focus resection. We set the region of interest (ROI) on the bilateral Brodmann areas 44 and 45 (BA 44 and 45). To compare the functional activity at both ROIs we calculated the language laterality index (LI) using the formula: [VL-VR]/[VL+VR]*100, where VL and VR indicated the number of activated voxels in the left and right ROIs, respectively. RESULTS: As 2 patients were excluded due to the lack of activation in either ROI, the final study population consisted of 26 patients. By the Wada test, HLD was left in 20, right in 3, and equivocal in 3. At a cut-off of LI+50, the predictive sensitivity and specificity for left HLD were 85% (17/20) and 100%; right HLD was predicted in a single patient (sensitivity 33.3%, specificity 100%). CONCLUSION: The fMRI using the Shiritori task showed good activation in ROI of BA 44 and 45. At a cut-off of LI+50, LI of BA 44 and 45 predicted HLD identified by the Wada test with high specificity. PMID- 27185363 TI - Phosphate starvation induces DNA methylation in the vicinity of cis-acting elements known to regulate the expression of phosphate-responsive genes. AB - Phosphate (Pi) limitation is a constraint for plant growth in many natural and agricultural ecosystems. Plants possess adaptive mechanisms that enable them to cope with conditions of limited Pi supply, including a highly regulated genetic program controlling the expression of genes involved in different metabolic, signaling and development processes of plants. Recently, we showed that in response to phosphate limitation Arabidopsis thaliana sets specific DNA methylation patterns of genic features that often correlated with changes in gene expression. Our findings included, dynamic methylation changes in response to phosphate starvation and the observation that the expression of genes encoding DNA methyltransferases appear to be directly controlled by the key regulator PHOSPHATE RESPONSE 1 (PHR1). These results provide insight into how epigenetic marks can influence plant genomes and transcriptional programs to respond and adapt to harsh conditions. Here we present an analysis of DNA methylation in the upstream regions of low Pi responsive genes in Arabidopsis seedlings exposed to low Pi conditions. We found that hypo- and hyper-methylation in the vicinity of cognate binding sites for transcription factors known to regulate the phosphate starvation response clearly correlates with increased or decreased expression of low-Pi responsive genes. PMID- 27185364 TI - Coupled crystal orientation-size effects on the strength of nano crystals. AB - We study the combined effects of grain size and texture on the strength of nanocrystalline copper (Cu) and nickel (Ni) using a crystal-plasticity based mechanics model. Within the model, slip occurs in discrete slip events exclusively by individual dislocations emitted statistically from the grain boundaries. We show that a Hall-Petch relationship emerges in both initially texture and non-textured materials and our values are in agreement with experimental measurements from numerous studies. We find that the Hall-Petch slope increases with texture strength, indicating that preferred orientations intensify the enhancements in strength that accompany grain size reductions. These findings reveal that texture is too influential to be neglected when analyzing and engineering grain size effects for increasing nanomaterial strength. PMID- 27185366 TI - Validating Machine Learning Algorithms for Twitter Data Against Established Measures of Suicidality. AB - BACKGROUND: One of the leading causes of death in the United States (US) is suicide and new methods of assessment are needed to track its risk in real time. OBJECTIVE: Our objective is to validate the use of machine learning algorithms for Twitter data against empirically validated measures of suicidality in the US population. METHODS: Using a machine learning algorithm, the Twitter feeds of 135 Mechanical Turk (MTurk) participants were compared with validated, self-report measures of suicide risk. RESULTS: Our findings show that people who are at high suicidal risk can be easily differentiated from those who are not by machine learning algorithms, which accurately identify the clinically significant suicidal rate in 92% of cases (sensitivity: 53%, specificity: 97%, positive predictive value: 75%, negative predictive value: 93%). CONCLUSIONS: Machine learning algorithms are efficient in differentiating people who are at a suicidal risk from those who are not. Evidence for suicidality can be measured in nonclinical populations using social media data. PMID- 27185367 TI - Ultrastructural characterization of the pronephric glomerulus development in zebrafish. AB - The zebrafish pronephros is a valuable model for studying kidney development and diseases. Ultrastructural studies have revealed that zebrafish and mammals share similarities in nephron structures such as podocytes, slit diaphragms, glomerular basement membrane, and endothelium. However, the basic ultrastructural features of the pronephric glomerulus during glomerulogenesis have not been characterized. To understand these features, it is instructive to consider the developmental process of the pronephros glomerulus. Here, we describe the ultrastructural features of pronephric glomerulus in detail from 24 h hours post-fertilization (hpf) to 144 hpf, the period during which the pronephric glomerulus develops from initiation to its mature morphology. The pronephric glomerulus underwent progressive morphogenesis from 24 to 72 hpf, and presumptive glomerular cells were observed ventral to the aorta region at 24 hpf. The nascent glomerular basement membrane and initial lumen were formed at 36 hpf. A lumen was clearly visible in the region of the pronephros at 48 hpf. At 60 hpf, the pronephric glomerulus contained more patches of capillaries. After these transformations, the complex capillary vessel networks had formed inside the glomerulus, which was surrounded by podocyte bodies with elaborate foot processes as well as well formed glomerular basement membrane by 72 hpf. The number of renal glomerular cells rapidly increased, and the glomerulus presented its delicate structural features by 96 hpf. Morphogenesis was completed at 120 hpf with the final formation of the pronephric glomerulus. J. Morphol. 277:1104-1112, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27185368 TI - Rectal Cancer: Assessment of Neoadjuvant Chemoradiation Outcome based on Radiomics of Multiparametric MRI. AB - PURPOSE: To evaluate multiparametric MRI features in predicting pathologic response after preoperative chemoradiation therapy (CRT) for locally advanced rectal cancer (LARC). EXPERIMENTAL DESIGN: Forty-eight consecutive patients (January 2012-November 2014) receiving neoadjuvant CRT were enrolled. All underwent anatomical T1/T2, diffusion-weighted MRI (DWI) and dynamic contrast enhanced (DCE) MRI before CRT. A total of 103 imaging features, analyzed using both volume-averaged and voxelized methods, were extracted for each patient. Univariate analyses were performed to evaluate the capability of each individual parameter in predicting pathologic complete response (pCR) or good response (GR) evaluated based on tumor regression grade. Artificial neural network with 4-fold validation technique was further utilized to select the best predictor sets to classify different response groups and the predictive performance was calculated using receiver operating characteristic (ROC) curves. RESULTS: The conventional volume-averaged analysis could provide an area under ROC curve (AUC) ranging from 0.54 to 0.73 in predicting pCR. While if the models were replaced by voxelized heterogeneity analysis, the prediction accuracy measured by AUC could be improved to 0.71-0.79. Similar results were found for GR prediction. In addition, each subcategory images could generate moderate power in predicting the response, which if combining all information together, the AUC could be further improved to 0.84 for pCR and 0.89 for GR prediction, respectively. CONCLUSIONS: Through a systematic analysis of multiparametric MR imaging features, we are able to build models with improved predictive value over conventional imaging metrics. The results are encouraging, suggesting the wealth of imaging radiomics should be further explored to help tailoring the treatment into the era of personalized medicine. Clin Cancer Res; 22(21); 5256-64. (c)2016 AACR. PMID- 27185369 TI - Noninvasive Detection of Metastases and Follicle Density in Ovarian Tissue Using Full-Field Optical Coherence Tomography. AB - PURPOSE: Autotransplantation of ovarian tissue can be used to restore fertility in patients with cancer following gonadotoxic treatment. Whether this procedure is safe remains unclear, as current tumor detection methods render the ovarian tissue unsuitable for transplantation. Full-field optical coherence tomography (FF-OCT) is an imaging modality that rapidly produces high-resolution histology like images without the need to fix, freeze, or stain the tissue. In this proof of-concept study, we investigated whether FF-OCT can be used to detect metastases in ovarian tissue, thereby increasing the safety of ovarian tissue autotransplantation. We also evaluated whether cortical ovarian tissue and follicles remain viable following FF-OCT imaging. EXPERIMENTAL DESIGN: Formalin fixed, paraffin-embedded tissue samples were obtained from seven normal ovaries and fourteen ovaries containing metastases and/or micrometastases. These samples were deparaffinized and imaged using FF-OCT. The FF-OCT images were then compared with corresponding hematoxylin and eosin-stained tissue sections. Finally, we examined the effect of FF-OCT imaging on the viability of ovarian tissues and follicles in fresh bovine ovarian tissue using a glucose uptake and neutral red staining, respectively. RESULTS: FF-OCT illustrated both normal structures and metastases in ovarian tissue within minutes. Primordial follicles were readily identifiable. Finally, tissues and follicles remained viable following FF-OCT imaging for up to 180 and 60 minutes, respectively. CONCLUSIONS: FF-OCT imaging is a promising method for the noninvasive detection of metastases, including micrometastases, in ovarian tissue. Moreover, this method facilitates the selection of cortical ovarian tissue with the highest density of primordial follicles, potentially increasing the likelihood of restoring ovarian function following ovarian tissue autotransplantation. Clin Cancer Res; 22(22); 5506-13. (c)2016 AACR. PMID- 27185365 TI - STAT3 signaling in immunity. AB - The transcriptional regulator STAT3 has key roles in vertebrate development and mature tissue function including control of inflammation and immunity. Mutations in human STAT3 associate with diseases such as immunodeficiency, autoimmunity and cancer. Strikingly, however, either hyperactivation or inactivation of STAT3 results in human disease, indicating tightly regulated STAT3 function is central to health. Here, we attempt to summarize information on the numerous and distinct biological actions of STAT3, and highlight recent discoveries, with a specific focus on STAT3 function in the immune and hematopoietic systems. Our goal is to spur investigation on mechanisms by which aberrant STAT3 function drives human disease and novel approaches that might be used to modulate disease outcome. PMID- 27185370 TI - Intratumor Heterogeneity Affects Gene Expression Profile Test Prognostic Risk Stratification in Early Breast Cancer. AB - PURPOSE: To examine the effect of intratumor heterogeneity (ITH) on detection of genes within gene expression panels (GEPs) and the subsequent ability to predict prognostic risk. EXPERIMENTAL DESIGN: Multiplexed barcoded RNA analysis was used to measure the expression of 141 genes from five GEPs (Oncotype Dx, MammaPrint, PAM50, EndoPredict, and Breast Cancer Index) in breast cancer tissue sections and tumor-rich cores from 71 estrogen receptor (ER)-positive node-negative tumors, on which clinical Oncotype Dx testing was previously performed. If the tumor had foci of high Ki67 (n = 26), low/negative progesterone receptor (PR; n = 13), or both (n = 5), additional cores were obtained. In total, 181 samples were processed. Oncotype Dx recurrence scores were calculated from NanoString nCounter gene expression data. RESULTS: Hierarchical clustering using all GEP genes showed that majority (61 of 71) of tumor samples clustered by patient, indicating greater interpatient heterogeneity (IPH) than ITH. We found a strikingly high correlation between Oncotype Dx recurrence scores obtained from whole sections versus tumor-rich cores (r = 0.94). However, high Ki67 and low PR cores had slightly higher but not statistically significant recurrence scores. For 18 of 71 (25%) patients, scores were divergent between sections and cores and crossed the boundaries for low, intermediate, and high risk. CONCLUSIONS: Our study indicates that in patients with highly heterogeneous tumors, GEP recurrence scores from a single core could under- or overestimate prognostic risk. Hence, it may be a useful strategy to assess multiple samples (both representative and atypical cores) to fully account for the ITH-driven variation in risk prediction. Clin Cancer Res; 22(21); 5362-9. (c)2016 AACR. PMID- 27185371 TI - Depletion of FOXM1 via MET Targeting Underlies Establishment of a DNA Damage Induced Senescence Program in Gastric Cancer. AB - PURPOSE: Deregulated signaling via the MET receptor tyrosine kinase is abundant in gastric tumors, with up to 80% of cases displaying aberrant MET expression. A growing body of evidence suggests MET as a potential target for tumor radiosensitization. EXPERIMENTAL DESIGN: Cellular proliferation and DNA damage induced senescence were studied in a panel of MET-overexpressing human gastric cancer cell lines as well as in xenograft models after MET inhibition and/or ionizing radiation. Pathways activation and protein expression were assessed by immunoblotting and immunohistochemistry. Tumor tissue microarrays (91 gastric cancer patients) were generated and copy number alteration (178 patients) and gene expression (373 patients) data available at The Cancer Genome Atlas were analyzed to assess the coalterations of MET and FOXM1. RESULTS: MET targeting administered before ionizing radiation instigates DNA damage-induced senescence (~80%, P < 0.001) rather than cell death. MET inhibition-associated senescence is linked to the blockade of MAPK pathway, correlates with downregulation of FOXM1, and can be abrogated (11.8% vs. 95.3%, P < 0.001) by ectopic expression of FOXM1 in the corresponding gastric tumor cells. Cells with ectopic FOXM1 expression demonstrate considerable (~20%, P < 0.001) growth advantage despite MET targeting, suggesting a novel clinically relevant resistance mechanism to MET inhibition as the copresence of both MET and FOXM1 protein (33%) and mRNA (30%) overexpression as well as gene amplification (24,7%) are common in patients with gastric cancer. CONCLUSIONS: FOXM1, a negative regulator of senescence, has been identified as a key downstream effector and potential clinical biomarker that mediates MET signaling following infliction of DNA damage in gastric tumors. Clin Cancer Res; 22(21); 5322-36. (c)2016 AACR. PMID- 27185373 TI - Use of Liquid Biopsies in Clinical Oncology: Pilot Experience in 168 Patients. AB - PURPOSE: There is a growing interest in using circulating tumor DNA (ctDNA) testing in patients with cancer. EXPERIMENTAL DESIGN: A total of 168 patients with diverse cancers were analyzed. Patients had digital next-generation sequencing (54 cancer-related gene panel including amplifications in ERBB2, EGFR, and MET) performed on their plasma. Type of genomic alterations, potential actionability, concordance with tissue testing, and patient outcome were examined. RESULTS: Fifty-eight percent of patients (98/168) had >=1 ctDNA alteration(s). Of the 98 patients with alterations, 71.4% had >= 1 alteration potentially actionable by an FDA-approved drug. The median time interval between the tissue biopsy and the blood draw was 2.7 months for patients with >= 1 alteration in common compared with 14.4 months (P = 0.006) for the patients in whom no common alterations were identified in the tissue and plasma. Overall concordance rates for tissue and ctDNA were 70.3% for TP53 and EGFR, 88.1% for PIK3CA, and 93.1% for ERBB2 alterations. There was a significant correlation between the cases with >= 1 alteration with ctDNA >= 5% and shorter survival (median = 4.03 months vs. not reached at median follow-up of 6.1 months; P < 0.001). Finally, 5 of the 12 evaluable patients (42%) matched to a treatment targeting an alteration(s) detected in their ctDNA test achieved stable disease >= 6 months/partial remission compared with 2 of 28 patients (7.1%) for the unmatched patients, P = 0.02. CONCLUSIONS: Our initial study demonstrates that ctDNA tests provide information complementary to that in tissue biopsies and may be useful in determining prognosis and treatment. Clin Cancer Res; 22(22); 5497 505. (c)2016 AACR. PMID- 27185372 TI - TransCONFIRM: Identification of a Genetic Signature of Response to Fulvestrant in Advanced Hormone Receptor-Positive Breast Cancer. AB - PURPOSE: Fulvestrant is an estrogen receptor (ER) antagonist and an approved treatment for metastatic estrogen receptor-positive (ER+) breast cancer. With the exception of ER levels, there are no established predictive biomarkers of response to single-agent fulvestrant. We attempted to identify a gene signature of response to fulvestrant in advanced breast cancer. EXPERIMENTAL DESIGN: Primary tumor samples from 134 patients enrolled in the phase III CONFIRM study of patients with metastatic ER+ breast cancer comparing treatment with either 250 mg or 500 mg fulvestrant were collected for genome-wide transcriptomic analysis. Gene expression profiling was performed using Affymetrix microarrays. An exploratory analysis was performed to identify biologic pathways and new signatures associated with response to fulvestrant. RESULTS: Pathway analysis demonstrated that increased EGF pathway and FOXA1 transcriptional signaling is associated with decreased response to fulvestrant. Using a multivariate Cox model, we identified a novel set of 37 genes with an expression that is independently associated with progression-free survival (PFS). TFAP2C, a known regulator of ER activity, was ranked second in this gene set, and high expression was associated with a decreased response to fulvestrant. The negative predictive value of TFAP2C expression at the protein level was confirmed by IHC. CONCLUSIONS: We identified biologic pathways and a novel gene signature in primary ER+ breast cancers that predicts for response to treatment in the CONFIRM study. These results suggest potential new therapeutic targets and warrant further validation as predictive biomarkers of fulvestrant treatment in metastatic breast cancer. Clin Cancer Res; 22(23); 5755-64. (c)2016 AACR. PMID- 27185374 TI - ACRIN 6684: Assessment of Tumor Hypoxia in Newly Diagnosed Glioblastoma Using 18F FMISO PET and MRI. AB - PURPOSE: Structural and functional alterations in tumor vasculature are thought to contribute to tumor hypoxia which is a primary driver of malignancy through its negative impact on the efficacy of radiation, immune surveillance, apoptosis, genomic stability, and accelerated angiogenesis. We performed a prospective, multicenter study to test the hypothesis that abnormal tumor vasculature and hypoxia, as measured with MRI and PET, will negatively impact survival in patients with newly diagnosed glioblastoma. EXPERIMENTAL DESIGN: Prior to the start of chemoradiation, patients with glioblastoma underwent MRI scans that included dynamic contrast enhanced and dynamic susceptibility contrast perfusion sequences to quantitate tumor cerebral blood volume/flow (CBV/CBF) and vascular permeability (ktrans) as well as 18F-Fluoromisonidazole (18F-FMISO) PET to quantitate tumor hypoxia. ROC analysis and Cox regression models were used to determine the association of imaging variables with progression-free and overall survival. RESULTS: Fifty patients were enrolled of which 42 had evaluable imaging data. Higher pretreatment 18F-FMISO SUVpeak (P = 0.048), mean ktrans (P = 0.024), and median ktrans (P = 0.045) were significantly associated with shorter overall survival. Higher pretreatment median ktrans (P = 0.021), normalized RCBV (P = 0.0096), and nCBF (P = 0.038) were significantly associated with shorter progression-free survival. SUVpeak [AUC = 0.75; 95% confidence interval (CI), 0.59-0.91], nRCBV (AUC = 0.72; 95% CI, 0.56-0.89), and nCBF (AUC = 0.72; 95% CI, 0.56-0.89) were predictive of survival at 1 year. CONCLUSIONS: Increased tumor perfusion, vascular volume, vascular permeability, and hypoxia are negative prognostic markers in newly diagnosed patients with gioblastoma, and these important physiologic markers can be measured safely and reliably using MRI and 18F-FMISO PET. Clin Cancer Res; 22(20); 5079-86. (c)2016 AACR. PMID- 27185378 TI - Estimation of design space for an extrusion-spheronization process using response surface methodology and artificial neural network modelling. AB - The application of the Quality by Design principles is one of the key issues of the recent pharmaceutical developments. In the past decade a lot of knowledge was collected about the practical realization of the concept, but there are still a lot of unanswered questions. The key requirement of the concept is the mathematical description of the effect of the critical factors and their interactions on the critical quality attributes (CQAs) of the product. The process design space (PDS) is usually determined by the use of design of experiment (DoE) based response surface methodologies (RSM), but inaccuracies in the applied polynomial models often resulted in the over/underestimation of the real trends and changes making the calculations uncertain, especially in the edge regions of the PDS. The completion of RSM with artificial neural network (ANN) based models is therefore a commonly used method to reduce the uncertainties. Nevertheless, since the different researches are focusing on the use of a given DoE, there is lack of comparative studies on different experimental layouts. Therefore, the aim of present study was to investigate the effect of the different DoE layouts (2 level full factorial, Central Composite, Box-Behnken, 3 level fractional and 3 level full factorial design) on the model predictability and to compare model sensitivities according to the organization of the experimental data set. It was revealed that the size of the design space could differ more than 40% calculated with different polynomial models, which was associated with a considerable shift in its position when higher level layouts were applied. The shift was more considerable when the calculation was based on RSM. The model predictability was also better with ANN based models. Nevertheless, both modelling methods exhibit considerable sensitivity to the organization of the experimental data set, and the use of design layouts is recommended, where the extreme values factors are more represented. PMID- 27185377 TI - COBLL1, LPL and ZAP70 expression defines prognostic subgroups of chronic lymphocytic leukemia patients with high accuracy and correlates with IGHV mutational status. AB - The clinical course of chronic lymphocytic leukemia (CLL) is highly variable. Patients with unmutated IGHV (U-CLL) usually progress rapidly, whereas patients with mutated IGHV (M-CLL) have a more indolent disease. The expression of several genes correlates closely with the IGHV mutational status and could be used to assess prognosis in CLL. We analyzed the prognostic relevance of COBLL1, LPL, and ZAP70 gene expression, which correlated with IGHV mutational status (p < 0.0001), in 117 CLL patients and established a prognostic parameter dividing the tested cohort according to the disease aggressiveness. Our prognostic parameter was validated on an independent cohort of 161 CLL patients and achieved a high accuracy (94%). Patients divided according to the prognostic parameter differ in overall survival and time to first treatment (p < 0.0001, HR = 2.300/5.970, 95% CI: 1.587-3.450/4.621-15.86). Our approach provides a reliable alternative method to prognosis assessment via IGHV mutational status analysis. PMID- 27185376 TI - Effects of human serum and apo-Transferrin on Staphylococcus epidermidis RP62A biofilm formation. AB - Biofilm-associated Staphylococcus epidermidis infections present clinically important features due to their high levels of resistance to traditional antibiotics. As a part of human innate immune system, serum shows different degrees of protection against systemic S. epidermidis infection. We investigated the ability of human serum as well as serum component to inhibit the formation of, and eradication of mature S. epidermidis biofilms. In addition, the synergistic effect of vancomycin combined with apo-Transferrin was checked. Human serum exhibited significant antibiofilm activities against S. epidermidis at the concentration without affecting planktonic cell growth. However, there was no effect of human serum on established biofilms. By component separation, we observed that antibiofilm effect of serum components mainly due to the proteins could be damaged by heat inactivation (e.g., complement) or heat-stable proteins >=100 kDa. In addition, serum apo-Transferrin showed modest antibiofilm effect, but without influence on S. epidermidis initial adhesion. And there was a synergistic antibiofilm interaction between vancomycin and apo-Transferrin against S. epidermidis. Our results indicate that serum or its components (heat inactivated components or heat-stable proteins >=100 kDa) could inhibits S. epidermidis biofilm formation. Besides, apo-Transferrin could partially reduce the biofilm formation at the concentration that does not inhibit planktonic cell growth. PMID- 27185375 TI - Baseline Biomarkers for Outcome of Melanoma Patients Treated with Pembrolizumab. AB - PURPOSE: Biomarkers for outcome after immune-checkpoint blockade are strongly needed as these may influence individual treatment selection or sequence. We aimed to identify baseline factors associated with overall survival (OS) after pembrolizumab treatment in melanoma patients. EXPERIMENTAL DESIGN: Serum lactate dehydrogenase (LDH), routine blood count parameters, and clinical characteristics were investigated in 616 patients. Endpoints were OS and best overall response following pembrolizumab treatment. Kaplan-Meier analysis and Cox regression were applied for survival analysis. RESULTS: Relative eosinophil count (REC) >=1.5%, relative lymphocyte count (RLC) >=17.5%, <=2.5-fold elevation of LDH, and the absence of metastasis other than soft-tissue/lung were associated with favorable OS in the discovery (n = 177) and the confirmation (n = 182) cohort and had independent positive impact (all P < 0.001). Their independent role was subsequently confirmed in the validation cohort (n = 257; all P < 0.01). The number of favorable factors was strongly associated with prognosis. One-year OS probabilities of 83.9% versus 14.7% and response rates of 58.3% versus 3.3% were observed in patients with four of four compared to those with none of four favorable baseline factors present, respectively. CONCLUSIONS: High REC and RLC, low LDH, and absence of metastasis other than soft-tissue/lung are independent baseline characteristics associated with favorable OS of patients with melanoma treated with pembrolizumab. Presence of four favorable factors in combination identifies a subgroup with excellent prognosis. In contrast, patients with no favorable factors present have a poor prognosis, despite pembrolizumab, and additional treatment advances are still needed. A potential predictive impact needs to be further investigated. Clin Cancer Res; 22(22); 5487-96. (c)2016 AACR. PMID- 27185379 TI - Thermosensitive hydrogel system assembled by PTX-loaded copolymer nanoparticles for sustained intraperitoneal chemotherapy of peritoneal carcinomatosis. AB - Intraperitoneal (IP) chemotherapy is a preferable treatment option for peritoneal carcinomatosis of malignancies by delivering chemotherapeutic drugs into the abdominal cavity. A persistent major challenge in IP chemotherapy is the need to provide effective drug concentration in the peritoneal cavity for an extended period of time. In the present work, the thermosensitive hydrogel system (PTX/PECT(gel)) assembled by PTX (paclitaxel)-loaded amphiphilic copolymer (PECT, poly (epsilon-caprolactone-co-1,4,8-trioxa [4.6]spiro-9-undecanone)-poly(ethylene glycol)-poly (epsilon-caprolactone-co-1,4,8-trioxa [4.6]spiro-9-undecanone)) nanoparticles was developed for sustained IP chemotherapy of peritoneal carcinomatosis model. Cytotoxicity assay indicated that PECT hydrogel was biocompatible with very low cytotoxicity and PTX/PECT(gel) had enhanced cytotoxicity than free PTX. In vivo toxicity study demonstrated the biocompatibility and biosafety of PECT hydrogel as an IP chemotherapy carrier. The fluorescence imaging method was employed to monitor the intraperitoneal degradation of PECT hydrogel by labeling PECT with rhodamine B. PECT hydrogel with the dose of 200MUL showed about 8days' retention time and most of the injected hydrogel was located in the intestine. The anti-tumor efficacy study was carried out in mice bearing CT26 intraperitoneal ascites fluid as colorectal peritoneal carcinomatosis model. The result showed that intraperitoneal administration of PTX/PECT(gel) could effectively suppress growth and metastasis of CT26 peritoneal carcinomatosis in vivo, compared with Taxol(r) group. The pharmacokinetic studies demonstrated that PTX/PECT(gel) could improve the bioavailability of PTX by being formulated in PECT hydrogel. Overall, sustained drug concentration at peritoneal levels in combination with drug in the form of nanoparticle contributes to the enhanced anti-tumor efficacy. Thus, our results suggested that PTX/PECT(gel) may have great potential applications in IP chemotherapy. PMID- 27185380 TI - Calreticulin mutation does not contribute to disease progression in essential thrombocythemia by inhibiting phagocytosis. AB - Somatic mutations of calreticulin (CALR) have been observed in many cases of essential thrombocythemia (ET) or primary myelofibrosis that harbor non-mutated Janus kinase 2 (JAK2). CALR mainly localizes within the endoplasmic reticulum lumen, but a small fraction of the total CALR pool is distributed over the cell surface. Cell surface CALR is known to transduce prophagocytic "eat me" signals to macrophages and acts as one of the important regulators for macrophage engulfment. In this study, we attempted to clarify whether mutant CALR may affect the threshold for macrophage engulfment and play an integral role in the pathogenesis of CALR-mutated ET. First, we compared the surface expression levels of CALR on hematopoietic stem and progenitor cells (HSPCs) and mature blood cells in patients with myeloproliferative neoplasms and found that the surface expression of mutant CALR did not change. Next, we compared the threshold for macrophage phagocytosis of each HSPC fraction and mature blood cells and found no significant change in the efficiency of macrophage engulfment. Our data suggest that CALR mutation does not affect sensitivity to phagocytosis by macrophages. Finally, we analyzed the phosphorylation statuses of molecules downstream of JAK2 at each HSPC level in patients with ET and found that CALR mutations activated the JAK-STAT pathway in a manner similar to that associated with JAK2 mutations. These results indicate that mutant CALR causes myeloproliferation because of the activation of JAK-STAT pathway and not by the inhibition of phagocytosis, which is similar to the myeloproliferation caused by JAK2 V617F mutation. PMID- 27185381 TI - Hematopoietic stem cell-specific GFP-expressing transgenic mice generated by genetic excision of a pan-hematopoietic reporter gene. AB - Selective labeling of specific cell types by expression of green fluorescent protein (GFP) within the hematopoietic system would have great utility in identifying, localizing, and tracking different cell populations in flow cytometry, microscopy, lineage tracing, and transplantation assays. In this report, we describe the generation and characterization of a new transgenic mouse line with specific GFP labeling of all nucleated hematopoietic cells and platelets. This new "Vav-GFP" mouse line labels the vast majority of hematopoietic cells with GFP during both embryonic development and adulthood, with particularly high expression in hematopoietic stem and progenitor cells (HSPCs). With the exception of transient labeling of fetal endothelial cells, GFP expression is highly selective for hematopoietic cells and persists in donor derived progeny after transplantation of HSPCs. Finally, we also demonstrate that the loxP-flanked reporter allows for specific GFP labeling of different hematopoietic cell subsets when crossed to various Cre reporter lines. By crossing Vav-GFP mice to Flk2-Cre mice, we obtained robust and highly selective GFP expression in hematopoietic stem cells (HSCs). These data describe a new mouse model capable of directing GFP labeling exclusively of hematopoietic cells or exclusively of HSCs. PMID- 27185382 TI - Ni (II) adsorption onto Chrysanthemum indicum: Influencing factors, isotherms, kinetics, and thermodynamics. AB - The study explores the adsorption potential of Chrysanthemum indicum biomass for nickel ion removal from aqueous solution. C. indicum flowers in raw (CIF-I) and biochar (CIF-II) forms were used as adsorbents in this study. Batch experiments were conducted to ascertain the optimum conditions of solution pH, adsorbent dosage, contact time, and temperature for varying initial Ni(II) ion concentrations. Surface area, surface morphology, and functionality of the adsorbents were characterized by Brunauer, Emmett, and Teller (BET) surface analysis, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and Fourier transform infrared spectroscopy (FTIR). Adsorption kinetics were modeled using pseudo-first order, pseudo-second order, Elovich, intraparticle diffusion, Bangham's, and Boyd's plot. The equilibrium data were modeled using Langmuir, Freundlich, Temkin, and Dubinin-Radushkevich (D R) isotherm models. Experimental data provided the best fit to pseudo-second order kinetic model and Langmuir isotherm model for the adsorption of Ni(II) ion on both CIF-I and CIF-II with maximum adsorption capacities of 23.97 and 44.02 mg g(-1), respectively. Thermodynamic analysis of the data proved the process to be spontaneous and endothermic in nature. Desorption studies were conducted to evaluate the possibility of reusing the adsorbents. Findings of the present study provide substantial evidence for the use of C. indicum flower as an eco-friendly and potential adsorbent for the removal of Ni(II) ions from aqueous solution. PMID- 27185384 TI - A Palladium-Binding Deltarhodopsin for Light-Activated Conversion of Protonic to Electronic Currents. AB - Fusion of a palladium-binding peptide to an archaeal rhodopsin promotes intimate integration of the lipid-embedded membrane protein with a palladium hydride protonic contact. Devices fabricated with the palladium-binding deltarhodopsin enable light-activated conversion of protonic currents to electronic currents with on/off responses complete in seconds and a nearly tenfold increase in electrical signal relative to those made with the wild-type protein. PMID- 27185385 TI - Feasibility demonstration of a massively parallelizable optical near-field sensor for sub-wavelength defect detection and imaging. AB - To detect and resolve sub-wavelength features at optical frequencies, beyond the diffraction limit, requires sensors that interact with the electromagnetic near field of those features. Most instruments operating in this modality scan a single detector element across the surface under inspection because the scattered signals from a multiplicity of such elements would end up interfering with each other. However, an alternative massively parallelized configuration, capable of interrogating multiple adjacent areas of the surface at the same time, was proposed in 2002. Full physics simulations of the photonic antenna detector element that enables this instrument, show that using conventional red laser light (in the 600 nm range) the detector magnifies the signal from an 8 nm particle by up to 1.5 orders of magnitude. The antenna is a shaped slot element in a 60 nm silver film. The ability of this detector element to resolve lambda/78 objects is confirmed experimentally at radio frequencies by fabricating an artificial material structure that mimics the optical permittivity of silver scaled to 2 GHz, and "cutting" into it the slot antenna. The experimental set-up is also used to demonstrate the imaging of a patterned surface in which the critical dimensions of the pattern are lambda/22 in size. PMID- 27185383 TI - Bioinformatics for the synthetic biology of natural products: integrating across the Design-Build-Test cycle. AB - Covering: 2000 to 2016Progress in synthetic biology is enabled by powerful bioinformatics tools allowing the integration of the design, build and test stages of the biological engineering cycle. In this review we illustrate how this integration can be achieved, with a particular focus on natural products discovery and production. Bioinformatics tools for the DESIGN and BUILD stages include tools for the selection, synthesis, assembly and optimization of parts (enzymes and regulatory elements), devices (pathways) and systems (chassis). TEST tools include those for screening, identification and quantification of metabolites for rapid prototyping. The main advantages and limitations of these tools as well as their interoperability capabilities are highlighted. PMID- 27185386 TI - Morphological and quantitative evaluation of emphysema in chronic obstructive pulmonary disease patients: A comparative study of MRI with CT. AB - PURPOSE: To further validate the ability of ultrashort echo-time (UTE) magnetic resonance imaging (MRI) in quantifying lung density in patients diagnosed with chronic obstructive pulmonary disease (COPD) and to develop an MRI-based emphysema index (EI). MATERIALS AND METHODS: Ten subjects clinically diagnosed with COPD (5M/5F, age 62.6 +/- 8.5 years) and ten healthy subjects (2M/8F, age 48.9 +/- 19.2 years) were imaged via UTE MRI at 3T (4 mm slices, 1.39 * 1.39 mm2 pixels). Chest computed tomography (CT) images (generally 5 mm slices, ~0.55 * 0.55 mm2 pixels), acquired retrospectively, were compared to UTE MRI. CT lung densities, MR lung-signal density, and EI were quantified from both CT and UTE MR images via a quantitative automated analysis and compared to the percent predicted forced expiratory volume in 1 second (FEV1 % predicted). RESULTS: EI quantified in controls via CT and UTE MRI was 0.23 +/- 0.78% and 2.40 +/- 1.50%, respectively; in COPD subjects it was 13.3 +/- 14.9% (P = 0.021) and 12.0 +/- 9.8% (P = 0.013), respectively. Bland-Altman determined the mean differences and 95% limits of agreement for COPD subjects and healthy controls were 0.06 (12.50 to -12.38). Strong correlation (R2 = 0.79, P < 0.0001) existed between EIs quantified from both CT and UTE MRI. There was a slightly higher correlation between FEV1 % predicted and the UTE MRI EI (R2 = 0.65, P < 0.0001) compared to CT EI (R2 = 0.49, P < 0.0001). CONCLUSION: Our results demonstrate a significant positive correlation between lung density and EI assessed with CT and MRI. Furthermore, UTE MRI exhibits its potential as a diagnostic alternative to CT for assessing the extent and the severity of emphysema, particularly for longitudinal studies. J. Magn. Reson. Imaging 2016;44:1656-1663. PMID- 27185388 TI - The role of alkali metal cations in the stabilization of guanine quadruplexes: why K(+) is the best. AB - The alkali metal ion affinity of guanine quadruplexes has been studied using dispersion-corrected density functional theory (DFT-D). We have done computational investigations in aqueous solution that mimics artificial supramolecular conditions where guanine bases assemble into stacked quartets as well as biological environments in which telomeric quadruplexes are formed. In both cases, an alkali metal cation is needed to assist self-assembly. Our quantum chemical computations on these supramolecular systems are able to reproduce the experimental order of affinity of the guanine quadruplexes for the cations Li(+), Na(+), K(+), Rb(+), and Cs(+). The strongest binding is computed between the potassium cation and the quadruplex as it occurs in nature. The desolvation and the size of alkali metal cations are thought to be responsible for the order of affinity. Until now, the relative importance of these two factors has remained unclear and debated. By assessing the quantum chemical 'size' of the cation, determining the amount of deformation of the quadruplex needed to accommodate the cation and through the energy decomposition analysis (EDA) of the interaction energy between the cation and the guanines, we reveal that the desolvation and size of the alkali metal cation are both almost equally responsible for the order of affinity. PMID- 27185387 TI - Examination of an intervention to enhance relationship satisfaction after brain injury: A feasibility study. AB - BACKGROUND: Brain injury (BI) can adversely affect marriage satisfaction, which can impact rehabilitation outcomes. The objectives of this study were to (1) examine the feasibility of providing a group intervention to individuals with BI and (2) examine if improvements occur in relationship satisfaction and communication following participation. METHODS: Nine individuals with BI and their partner participated in a 16-week group intervention targeting relationship skills training. Feedback and satisfaction questionnaires were created to assess feasibility and a pre- and post-test design was used to measure relationship satisfaction and communication. RESULTS: Couples reported high satisfaction with the intervention and workbook and would recommend this intervention to other couples who experience BI. The majority reported satisfaction with the length of treatment, although some felt it was too long. Three couples dropped from the study due to severe cognitive deficits or relationship distress. Couples reported significantly improved satisfaction and quality of relationship and reduced negative communication following the intervention. CONCLUSIONS: This intervention may incorporate an appropriate framework for helping couples enhance relationship satisfaction after BI. Given the feasibility and potential for benefit, the hypothesized efficacy of the intervention deserves testing through rigorous research methods, as focusing on improving relationships after a BI could potentially optimize rehabilitation outcomes. ABBREVIATIONS: TBI, Traumatic Brain Injury; BI, Brain Injury; CBT, Cognitive-Behavioural Therapy; DBT, Dialectical Behavioural Therapy. PMID- 27185389 TI - Are bicortical screw and plate osteosynthesis techniques equal in providing skeletal stability with the bilateral sagittal split osteotomy when used for mandibular advancement surgery? A systematic review and meta-analysis. AB - The objective of this study was to perform a systematic review and meta-analysis to test the null hypothesis that there is no difference in postoperative skeletal stability between bicortical screw and monocortical plate fixation after mandibular advancement surgery with bilateral sagittal split ramus osteotomy (BSSO). A comprehensive search of major databases (PubMed, EMBASE, and Cochrane CENTRAL) was conducted to locate all relevant articles published from inception to October 2015. Studies were selected based on inclusion criteria; randomized controlled trials, controlled clinical trials, and retrospective studies comparing bicortical screw vs. monocortical plate fixation after BSSO, reported in peer-reviewed publications in the English language, were considered eligible. Changes in linear measurements (horizontal and vertical) were analyzed. Five relevant studies were identified, involving 203 patients (bicortical screw n=98, monocortical plate n=105). No significant difference was found between monocortical plate and bicortical screw fixation in horizontal (P=0.099) or vertical measurement (P=0.882). Based on this review, there is overall agreement in the literature that the amount of advancement has a direct relationship with postoperative changes. The results of this meta-analysis support the hypothesis that there is no statistically significant difference in skeletal stability between bicortical screw and monocortical plate fixation of the BSSO following mandibular advancement surgery. PMID- 27185391 TI - Palliating inside the lines: The effects of borders and boundaries on palliative care in rural Canada. AB - We draw lines to divide our world into specific places, territories, and categories. Although borders and boundaries are dynamic and socially constructed, their existence creates many broad impacts on our lives by geographically distinguishing between groups (e.g., us/them; here/there; inside/outside) at various scales from the national down to the personal spaces of the individual. Particularly, borders and boundaries can be used to define a variety of differing spaces such as the familial, social, economic, political, as well as issues of access - including access to health services. Despite the implicit connection between borders, boundaries, and health, little research has investigated this connection from a health geography perspective. As such, this secondary thematic analysis contributes to addressing this notable gap by examining how borders and boundaries are experienced and perceived to impact access to palliative care in rural Canada from the perspectives of the formal and informal providers of such care. Drawing upon data from qualitative interviews (n = 40) with formal and informal palliative caregivers residing in four different rural Canadian communities, five forms of borders and boundaries were found to directly impact care delivery/receipt: political; jurisdictional; geographical; professional; and cultural. Implicitly and explicitly, participants discussed these borders and boundaries while sharing their experiences of providing palliative care in rural Canada. We conclude by discussing the implications of our findings for palliative care in rural Canada, while also emphasizing the need for more health geography, and related social science, researchers to recognize the significance of borders and boundaries in relation to health and healthcare delivery. Lastly, we emphasize the transferability of these findings to other health sectors, geographical settings, and disciplines. PMID- 27185390 TI - Optimize the interactions at S4 with efficient inhibitors targeting 3C proteinase from enterovirus 71. AB - Enterovirus 71 (EV71) is the causative agent of hand, foot and mouth disease and can spread its infections to the central nervous and other systems with severe consequences. The replication of EV71 depends on its 3C proteinase (3Cpro ), a significant drug target. By X-ray crystallography and functional assays, the interactions between inhibitors and EV71 3Cpro were evaluated. It was shown that improved interactions at S4 for the substrate binding could significantly enhance the potency. A new series of potent inhibitors with high ligand efficiency was generated for developing antivirals to treat and control the EV71-associated diseases. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27185393 TI - Bolder Takes All and the Role of Epigenetics. A Comment on Canestrelli et al. PMID- 27185394 TI - Humanity's Dual Response to Dogs and Wolves. AB - Dogs were first domesticated 31 000-41 000 years ago. Humanity has experienced ecological costs and benefits from interactions with dogs and wolves. We propose that humans inherited a dual response of attraction or aversion that expresses itself independently to domestic and wild canids. The dual response has had far reaching consequences for the ecology and evolution of all three taxa, including today's global 'ecological paw print' of 1 billion dogs and recent eradications of wolves. PMID- 27185395 TI - Historical Biogeography and the (Epi)Genetic Architecture of Animal Personality: A Comment on Cobben and van Oers. PMID- 27185392 TI - Bile acids-mediated overexpression of MUC4 via FAK-dependent c-Jun activation in pancreatic cancer. AB - The majority of pancreatic cancer (PC) patients are clinically presented with obstructive jaundice with elevated levels of circulatory bilirubin and alkaline phosphatases. In the current study, we examined the implications of bile acids (BA), an important component of bile, on the pathophysiology of PC and investigated their mechanistic association in tumor-promoting functions. Integration of results from PC patient samples and autochthonous mouse models showed an elevated levels of BA (p < 0.05) in serum samples compared to healthy controls. Similarly, an elevated BA levels was observed in pancreatic juice derived from PC patients (p < 0.05) than non-pancreatic non-healthy (NPNH) controls, further establishing the clinical association of BA with the pathogenesis of PC. The tumor-promoting functions of BA were established by observed transcriptional upregulation of oncogenic MUC4 expression. Luciferase reporter assay revealed distal MUC4 promoter as the primary responsive site to BA. In silico analysis recognized two c-Jun binding sites at MUC4 distal promoter, which was biochemically established using ChIP assay. Interestingly, BA treatment led to an increased transcription and activation of c-Jun in a FAK dependent manner. Additionally, BA receptor, namely FXR, which is also upregulated at transcriptional level in PC patient samples, was demonstrated as an upstream molecule in BA-mediated FAK activation, plausibly by regulating Src activation. Altogether, these results demonstrate that elevated levels of BA increase the tumorigenic potential of PC cells by inducing FXR/FAK/c-Jun axis to upregulate MUC4 expression, which is overexpressed in pancreatic tumors and is known to be associated with progression and metastasis of PC. PMID- 27185396 TI - Review of Antibiotic and Non-Antibiotic Properties of Beta-lactam Molecules. AB - BACKGROUND: Beta-lactam molecules are a family of drugs commonly used for their antibiotic properties; however, recent research has shown that several members of this group present a large number of other effects such as neuroprotective, antioxidant, analgesic or immunomodulatory capabilities. These properties have been used in both preclinical and clinical studies in different diseases such as hypoxic neuronal damage or acute and chronic pain. The present work briefly reviews the antibiotic effect of these molecules, and will then focus specially on the non-antibiotic effects of three beta-lactam subfamilies: penicillins, cephalosporins and beta lactamase inhibitors, each of which have different molecular structure and pharmacokinetics and therefore have several potential clinical applications. METHODS: A thorough search of bibliographic databases for peer-reviewed research was performed including only classic experiments or high quality reviews for the antibiotic mechanisms of beta-lactam molecules and only experimental research papers where included when the non-antibiotic properties of these molecules were searched. Only published articles from indexed journals were included. Quality of retrieved papers was assessed using standard tools. The characteristics of screened papers were described and findings of included studies were contextualized to either a mechanistic or a clinical framework. RESULTS: Seventy-eight papers were included in the review; the majority (56) were relative to the non-antibiotic properties of beta-lactam molecules. The non antibiotic effects reviewed were divided accordingly to the amount of information available for each one. Twelve papers outlined the epileptogenic effects induced by beta-lactam molecules administration; these included both clinical and basic research as well as probable mechanistic explanations. Eighteen papers described a potential neuroprotective effect, mostly in basic in vitro and in vivo experiments. Analgesic properties where identified in twelve papers and basic research was described alongside with both experimental and serendipic clinical findings. Seven papers described a down-regulation effect exerted by beta-lactam molecules administration in different addiction animal models. Finally other effects such as penile erection, dopamine release facilitation and anti-neoplasic effects where described from seven papers. CONCLUSION: The findings of this review show that beta-lactam molecules may induce several effects, which may be clinically relevant in a lot of different diseases. This paper is, to our knowledge, the first comprehensive review of the non-antibiotic effects shown by beta-lactam molecules and may help increase the interest in this field, which may result in a direct translation of this effects to a clinical context. PMID- 27185397 TI - Exhaustive Genome-Wide Search for SNP-SNP Interactions Across 10 Human Diseases. AB - The identification of statistical SNP-SNP interactions may help explain the genetic etiology of many human diseases, but exhaustive genome-wide searches for these interactions have been difficult, due to a lack of power in most datasets. We aimed to use data from the Resource for Genetic Epidemiology Research on Adult Health and Aging (GERA) study to search for SNP-SNP interactions associated with 10 common diseases. FastEpistasis and BOOST were used to evaluate all pairwise interactions among approximately N = 300,000 single nucleotide polymorphisms (SNPs) with minor allele frequency (MAF) >= 0.15, for the dichotomous outcomes of allergic rhinitis, asthma, cardiac disease, depression, dermatophytosis, type 2 diabetes, dyslipidemia, hemorrhoids, hypertensive disease, and osteoarthritis. A total of N = 45,171 subjects were included after quality control steps were applied. These data were divided into discovery and replication subsets; the discovery subset had > 80% power, under selected models, to detect genome-wide significant interactions (P < 10(-12)). Interactions were also evaluated for enrichment in particular SNP features, including functionality, prior disease relevancy, and marginal effects. No interaction in any disease was significant in both the discovery and replication subsets. Enrichment analysis suggested that, for some outcomes, interactions involving SNPs with marginal effects were more likely to be nominally replicated, compared to interactions without marginal effects. If SNP-SNP interactions play a role in the etiology of the studied conditions, they likely have weak effect sizes, involve lower-frequency variants, and/or involve complex models of interaction that are not captured well by the methods that were utilized. PMID- 27185399 TI - mCAL: A New Approach for Versatile Multiplex Action of Cas9 Using One sgRNA and Loci Flanked by a Programmed Target Sequence. AB - Genome editing exploiting CRISPR/Cas9 has been adopted widely in academia and in the biotechnology industry to manipulate DNA sequences in diverse organisms. Molecular engineering of Cas9 itself and its guide RNA, and the strategies for using them, have increased efficiency, optimized specificity, reduced inappropriate off-target effects, and introduced modifications for performing other functions (transcriptional regulation, high-resolution imaging, protein recruitment, and high-throughput screening). Moreover, Cas9 has the ability to multiplex, i.e., to act at different genomic targets within the same nucleus. Currently, however, introducing concurrent changes at multiple loci involves: (i) identification of appropriate genomic sites, especially the availability of suitable PAM sequences; (ii) the design, construction, and expression of multiple sgRNA directed against those sites; (iii) potential difficulties in altering essential genes; and (iv) lingering concerns about "off-target" effects. We have devised a new approach that circumvents these drawbacks, as we demonstrate here using the yeast Saccharomyces cerevisiae First, any gene(s) of interest are flanked upstream and downstream with a single unique target sequence that does not normally exist in the genome. Thereafter, expression of one sgRNA and cotransformation with appropriate PCR fragments permits concomitant Cas9-mediated alteration of multiple genes (both essential and nonessential). The system we developed also allows for maintenance of the integrated, inducible Cas9 expression cassette or its simultaneous scarless excision. Our scheme-dubbed mCAL for " M: ultiplexing of C: as9 at A: rtificial L: oci"-can be applied to any organism in which the CRISPR/Cas9 methodology is currently being utilized. In principle, it can be applied to install synthetic sequences into the genome, to generate genomic libraries, and to program strains or cell lines so that they can be conveniently (and repeatedly) manipulated at multiple loci with extremely high efficiency. PMID- 27185398 TI - UBR-5, a Conserved HECT-Type E3 Ubiquitin Ligase, Negatively Regulates Notch-Type Signaling in Caenorhabditis elegans. AB - Notch-type signaling mediates cell-cell interactions important for animal development. In humans, reduced or inappropriate Notch signaling activity is associated with various developmental defects and disease states, including cancers. Caenorhabditis elegans expresses two Notch-type receptors, GLP-1 and LIN 12. GLP-1 mediates several cell-signaling events in the embryo and promotes germline proliferation in the developing and adult gonad. LIN-12 acts redundantly with GLP-1 in certain inductive events in the embryo and mediates several cell cell interactions during larval development. Recovery of genetic suppressors and enhancers of glp-1 or lin-12 loss- or gain-of-function mutations has identified numerous regulators of GLP-1 and LIN-12 signaling activity. Here, we report the molecular identification of sog-1, a gene identified in screens for recessive suppressors of conditional glp-1 loss-of-function mutations. The sog-1 gene encodes UBR-5, the sole C. elegans member of the UBR5/Hyd family of HECT-type E3 ubiquitin ligases. Molecular and genetic analyses indicate that the loss of ubr-5 function suppresses defects caused by reduced signaling via GLP-1 or LIN-12. In contrast, ubr-5 mutations do not suppress embryonic or larval lethality associated with mutations in a downstream transcription factor, LAG-1. In the gonad, ubr-5 acts in the receiving cells (germ cells) to limit GLP-1 signaling activity. SEL-10 is the F-box component of SCF(SEL-10) E3 ubiquitin-ligase complex that promotes turnover of Notch intracellular domain. UBR-5 acts redundantly with SEL-10 to limit Notch signaling in certain tissues. We hypothesize that UBR-5 activity limits Notch-type signaling by promoting turnover of receptor or limiting its interaction with pathway components. PMID- 27185400 TI - Dynamics of a Novel Highly Repetitive CACTA Family in Common Bean (Phaseolus vulgaris). AB - Transposons are ubiquitous genomic components that play pivotal roles in plant gene and genome evolution. We analyzed two genome sequences of common bean (Phaseolus vulgaris) and identified a new CACTA transposon family named pvCACTA1. The family is extremely abundant, as more than 12,000 pvCACTA1 elements were found. To our knowledge, this is the most abundant CACTA family reported thus far. The computational and fluorescence in situ hybridization (FISH) analyses indicated that the pvCACTA1 elements were concentrated in terminal regions of chromosomes and frequently generated AT-rich 3 bp target site duplications (TSD, WWW, W is A or T). Comparative analysis of the common bean genomes from two domesticated genetic pools revealed that new insertions or excisions of pvCACTA1 elements occurred after the divergence of the two common beans, and some of the polymorphic elements likely resulted in variation in gene sequences. pvCACTA1 elements were detected in related species but not outside the Phaseolus genus. We calculated the molecular evolutionary rate of pvCACTA1 transposons using orthologous elements that indicated that most transposition events likely occurred before the divergence of the two gene pools. These results reveal unique features and evolution of this new transposon family in the common bean genome. PMID- 27185402 TI - Stroke increases the risk of hip fracture: a systematic review and meta-analysis. AB - Many studies have investigated the association between stroke and hip fracture risk, but the precise association was still unclear due to insufficient statistical power in single studies with relatively small sample size. Thus, we firstly conducted a meta-analysis of all published studies to precisely estimate the relationship of stroke with hip fracture risk. The strength for this relationship was weighed by pooled relative risks (RRs) with 95 % confidence intervals (95 % CIs) after adjustment for confounding variables. Stratified analyses by study design and ethnicity and sensitivity analysis were also performed. Two investigators independently performed a comprehensive literature search in databases of PubMed, Embase, and Wanfang for eligible articles. A Bayesian meta-analysis was also performed to get a more precise assessment of the relationship. Eleven relevant studies from 10 publications were finally included into our meta-analysis according to the inclusion criteria. Overall, stroke significantly and independently increased the risk of hip fracture (RR = 2.06, 95 % CI 1.68-2.52, P < 0.001). Bayesian meta-analysis showed that stroke was also associated with an over two-fold increased risk of hip fracture (RR = 2.11, 95 % CI 1.62-2.75). In stratified analysis, stroke could increase the risk of hip fracture in Caucasians (RR = 2.36, 95 % CI 1.83-3.05, P < 0.001). These data support the notion that stroke is an independent risk factor for hip fracture, and patients with stroke have a two-fold increased risk of hip fracture than those without stroke. PMID- 27185401 TI - Altered Function of the DnaJ Family Cochaperone DNJ-17 Modulates Locomotor Circuit Activity in a Caenorhabditis elegans Seizure Model. AB - The highly conserved cochaperone DnaJ/Hsp40 family proteins are known to interact with molecular chaperone Hsp70, and can regulate many cellular processes including protein folding, translocation, and degradation. In studies of Caenorhabditis elegans locomotion mutants, we identified a gain-of-function (gf) mutation in dnj-17 closely linked to the widely used e156 null allele of C. elegans GAD (glutamic acid decarboxylase) unc-25 dnj-17 encodes a DnaJ protein orthologous to human DNAJA5. In C. elegans DNJ-17 is a cytosolic protein and is broadly expressed in many tissues. dnj-17(gf) causes a single amino acid substitution in a conserved domain, and behaves as a hypermorphic mutation. The effect of this dnj-17(gf) is most prominent in mutants lacking GABA synaptic transmission. In a seizure model caused by a mutation in the ionotropic acetylcholine receptor acr-2(gf), dnj-17(gf) exacerbates the convulsion phenotype in conjunction with absence of GABA. Null mutants of dnj-17 show mild resistance to aldicarb, while dnj-17(gf) is hypersensitive. These results highlight the importance of DnaJ proteins in regulation of C. elegans locomotor circuit, and provide insights into the in vivo roles of DnaJ proteins in humans. PMID- 27185404 TI - Infections in symptomatic travelers returning from the Arabian peninsula to France: A retrospective cross-sectional study. PMID- 27185405 TI - Malignant Melanoma of the Nail Apparatus: A Fluorescence In Situ Hybridization Analysis of 7 Cases. AB - Background Malignant melanoma of the nail apparatus is exceedingly rare. Increasingly, genetic studies have been employed to aid in distinguishing between malignant melanoma and benign melanocytic nevi. Methods Archived nail apparatus melanomas were analyzed by fluorescence in situ hybridization (FISH) using probes targeting the genes at 6p25 (RREB1), 11q13 (CCND1), 8q24.1 (MYC), 6q23 (MYB), 9p21 (CDKN2A) and the centromeres of chromosomes 8 (D8Z2) and 6 (D6Z1). The results were correlated with clinical and demographic information. Results Mean patient age was 57.8 years (range 23-92 years). In all, 5 of 7 (71%) cases involved the upper extremity digits. RREB1 gain was seen in all cases. CCND1 gain was seen in 6 of 7 (86%) cases, 3 of which were amplified. MYB loss and MYC gain were both seen in 5 of 7 (71%) cases. Homozygous loss of CDKN2A was not observed in any case. Two of 7 (28.6%) patients had lymph node metastasis and died of widely metastatic disease. These 2 patients harbored the most genetic aberrations: gains of RREB1, CCND1, and MYC, and MYB loss. Both benign melanocytic nevi controls showed normal FISH results. Conclusions RREB1 and CCND1 gains are common in nail apparatus melanoma as in most melanomas, and an increased number of genetic aberrations may be associated with a poorer prognosis, though the limited number of cases precludes definitive correlation. FISH appears to be a useful adjunct in the diagnosis of nail apparatus melanomas and improves diagnostic confidence even in the setting of unambiguous histomorphology. PMID- 27185403 TI - Imported brucellosis: A case series and literature review. AB - BACKGROUND: Brucellosis is one of the main neglected zoonotic diseases. Several factors may contribute to the epidemiology of brucellosis. Imported cases, mainly in travellers but also in recently arrived immigrants, and cases associated with imported products, appear to be infrequently reported. METHODS: Cases of brucellosis diagnosed at a referral unit for imported diseases in Europe were described and a review of the literature on imported cases and cases associated with contaminated imported products was performed. RESULTS: Most imported cases were associated with traditional risk factors such as travel/consumption of unpasteurized dairy products in endemic countries. Cases associated with importation of food products or infected animals also occurred. Although a lower disease incidence of brucellosis has been reported in developed countries, a higher incidence may still occur in specific populations, as illustrated by cases in Hispanic patients in the USA and in Turkish immigrants in Germany. Imported brucellosis appears to present with similar protean manifestations and both classical and infrequent modes of acquisition are described, leading on occasions to mis-diagnoses and diagnostic delays. CONCLUSIONS: Importation of Brucella spp. especially into non-endemic areas, or areas which have achieved recent control of both animal and human brucellosis, may have public health repercussions and timely recognition is essential. PMID- 27185406 TI - Physical activity increases after bariatric surgery, review finds. PMID- 27185407 TI - Validity and reliability of elastic resistance bands for measuring shoulder muscle strength. AB - Valid and reliable measurements of muscle strength are important in sport medicine. This study assesses concurrent validity and intrarater reliability (test-retest reliability) of elastic resistance bands for measuring shoulder muscle strength. Altogether, 50 healthy adults [mean age 36.0 (SD: 11.6), 29 women and 21 men] participated in testing and retesting 1-2 weeks later. The maximal elastic resistance (TheraBand) that each participant could hold for 3 s during standing bilateral shoulder abduction to 90 degrees was converted into torque and validated against gold standard maximal voluntary isometric contraction (MVC) (Vishay force transducer) performed unilaterally while lying supine. The intrarater reliability of both tests were high; for the MVC and elastic band test, respectively, ICC(3,1) was 0.98 (95% CI: 0.97-0.99) and 0.99 (95% CI: 0.98-1.00), and measurement error was 4.8% (95% CI: 3.7-5.9) and 4.7% (95% CI: 3.1-6.2). For concurrent validity, ICC(3,1) was 0.96 (95% CI: 0.95-0.98) and measurement error was 8.1% (95% CI: 6.6-9.6), and the elastic band test explained 93% of the variance in the MVC test. However, the elastic band test produced systematically lower torque values than the MVC [56.5 (SD: 26.8) vs 66.5 (SD: 25.5) Nm, P < 0.01]. In conclusion, the test for shoulder muscle strength using elastic resistance bands has excellent validity and reliability, but produces systematically lower torque values than MVC. The reason for the lower torque values may be that the elastic band test has an initial concentric phase and is performed bilaterally and standing upright. PMID- 27185409 TI - Malignant transformation of a tracheal chondroma: The second reported case and review of the literature. AB - Tracheal tumors are rare, representing only 0.2% of the respiratory tract malignancies. Chondrosarcoma arising in the trachea was first described in 1959 by Jackson et al. and since then only 20 cases have been described. We report the second documented case of malignant transformation from an endotracheal chondroma, in a 75-year-old woman, and review the literature. PMID- 27185410 TI - A case of Birt-Hogg-Dube syndrome. PMID- 27185411 TI - The Emotional Experience of Motherhood in Planned Lesbian Families in the South African Context: "... Look How Good a Job I'm Doing, Look How Amazing We Are". AB - This article focuses on lesbian mothers' emotional experience of motherhood. It forms part of a larger qualitative and exploratory study with 10 lesbian couples in South Africa on their lived experience of planned motherhood. The study is located in a feminist phenomenological framework. Semi-structured interviews were conducted and interview transcripts were analyzed using thematic analysis. Participants described many different emotions associated with new motherhood: hope, joy, love, anxiety, helplessness, exhaustion, and feeling companionship and togetherness as well as feeling compromised and deprived. Mothers described these emotions but also focused on the development of a new identity, that of being a mother. PMID- 27185412 TI - Combination of soya protein and polydextrose reduces energy intake and glycaemic response via modulation of gastric emptying rate, ghrelin and glucagon-like peptide-1 in Chinese. AB - The short-term effect of soya protein, polydextrose and their combination on energy intake (EI) was investigated in Chinese. In total, twenty-seven healthy, normotensive and lean Chinese men aged 21-40 years were given four different soyabean curd preloads with or without polydextrose. The study was a repeated measure, randomised, cross-over design. The consumption of high-protein soyabean curd alone or in addition with polydextrose as a preload led to greater reduction in EI at a subsequent meal. A similar observation was also found after intake of low-protein soyabean curd with polydextrose. The gut hormone responses mirrored the reduction in food intake. It appears that incorporation of polydextrose either with low- or high-protein soyabean curd could be a potential strategy to reduce EI and assist with weight management. The popular consumption of soyabean curd in Chinese makes it an ideal vehicle for incorporation of polydextrose. This evidence-based dietary approach can serve as a guideline for developing functional foods for weight reduction and weight maintenance. PMID- 27185408 TI - Mitochondrial genetic diversity, selection and recombination in a canine transmissible cancer. AB - Canine transmissible venereal tumour (CTVT) is a clonally transmissible cancer that originated approximately 11,000 years ago and affects dogs worldwide. Despite the clonal origin of the CTVT nuclear genome, CTVT mitochondrial genomes (mtDNAs) have been acquired by periodic capture from transient hosts. We sequenced 449 complete mtDNAs from a global population of CTVTs, and show that mtDNA horizontal transfer has occurred at least five times, delineating five tumour clades whose distributions track two millennia of dog global migration. Negative selection has operated to prevent accumulation of deleterious mutations in captured mtDNA, and recombination has caused occasional mtDNA re-assortment. These findings implicate functional mtDNA as a driver of CTVT global metastatic spread, further highlighting the important role of mtDNA in cancer evolution. PMID- 27185413 TI - Breakfast consumption and weight-loss maintenance: results from the MedWeight study. AB - Daily breakfast consumption is a common eating behaviour among people who have maintained their weight loss after weight-loss management. However, there is not a precise definition for breakfast in the literature. The purpose of this study was to investigate potential associations between breakfast consumption (based on several definitions) and weight-loss maintenance, as well as to explore differences in breakfast quality between individuals who managed to maintain part of the weight loss and in those who regained weight loss. The study sample consisted of 354 participants of the MedWeight study (age: 32 (sd 10) years, 61 % women) who had lost >=10 % of their initial body weight and either maintained the loss for >=1 year (maintainers, n 257) or regained weight loss (regainers, n 97). Participants completed online questionnaires and reported their dietary intake through two telephone 24-h recalls. Breakfast consumption was evaluated using twelve different definitions. The analysis indicated that breakfast consumption was associated with weight-loss maintenance only in men, when using self-reported breakfast consumption or the following breakfast definitions: (1) the first eating episode consumed at home and (2) the first eating episode consumed at home excluding caffeinated drinks. This association remained statistically significant even after adjustment for potential confounding factors. Thus, breakfast, the first eating episode of the day, when consumed at home, may be protective against weight regaining. PMID- 27185414 TI - Nudging consumers towards healthier choices: a systematic review of positional influences on food choice. AB - Nudging or 'choice architecture' refers to strategic changes in the environment that are anticipated to alter people's behaviour in a predictable way, without forbidding any options or significantly changing their economic incentives. Nudging strategies may be used to promote healthy eating behaviour. However, to date, the scientific evidence has not been systematically reviewed to enable practitioners and policymakers to implement, or argue for the implementation of, specific measures to support nudging strategies. This systematic review investigated the effect of positional changes of food placement on food choice. In total, seven scientific databases were searched using relevant keywords to identify interventions that manipulated food position (proximity or order) to generate a change in food selection, sales or consumption, among normal-weight or overweight individuals across any age group. From 2576 identified articles, fifteen articles comprising eighteen studies met our inclusion criteria. This review has identified that manipulation of food product order or proximity can influence food choice. Such approaches offer promise in terms of impacting on consumer behaviour. However, there is a need for high-quality studies that quantify the magnitude of positional effects on food choice in conjunction with measuring the impact on food intake, particularly in the longer term. Future studies should use outcome measures such as change in grams of food consumed or energy intake to quantify the impact on dietary intake and potential impacts on nutrition-related health. Research is also needed to evaluate potential compensatory behaviours secondary to such interventions. PMID- 27185417 TI - Investigation of acetone, butanol and carbon dioxide as new breath biomarkers for convenient and noninvasive diagnosis of obstructive sleep apnea syndrome. AB - The objective of the present study was to investigate whether analysis of carbon dioxide, acetone and/or butanol present in human breath can be used as a simple and noninvasive diagnosis method for obstructive sleep apnea syndrome (OSAS). For this purpose, overnight changes in the concentrations of these breath molecules were measured before and after sleep in 10 patients who underwent polysomnography and were diagnosed with OSAS, and were compared with the levels of these biomarkers determined after sleep in 10 healthy subjects. The concentrations of exhaled carbon dioxide were measured using external cavity laser-based off-axis cavity enhanced absorption spectroscopy, whereas the levels of exhaled acetone and butanol were determined using thermal desorption gas chromatography mass spectrometry. We observed no significant changes in the levels of exhaled acetone and carbon dioxide in OSAS patients after sleep compared with pre-sleep values and compared with those in healthy control subjects. However, for the first time, to our knowledge, analyses of expired air showed an increased concentration of butanol after sleep compared with that before sleep and compared with that in healthy subjects. These results suggest that butanol can be established as a potential biomarker to enable the convenient and noninvasive diagnosis of OSAS in the future. PMID- 27185415 TI - A systems biology pipeline identifies new immune and disease related molecular signatures and networks in human cells during microgravity exposure. AB - Microgravity is a prominent health hazard for astronauts, yet we understand little about its effect at the molecular systems level. In this study, we have integrated a set of systems-biology tools and databases and have analysed more than 8000 molecular pathways on published global gene expression datasets of human cells in microgravity. Hundreds of new pathways have been identified with statistical confidence for each dataset and despite the difference in cell types and experiments, around 100 of the new pathways are appeared common across the datasets. They are related to reduced inflammation, autoimmunity, diabetes and asthma. We have identified downregulation of NfkappaB pathway via Notch1 signalling as new pathway for reduced immunity in microgravity. Induction of few cancer types including liver cancer and leukaemia and increased drug response to cancer in microgravity are also found. Increase in olfactory signal transduction is also identified. Genes, based on their expression pattern, are clustered and mathematically stable clusters are identified. The network mapping of genes within a cluster indicates the plausible functional connections in microgravity. This pipeline gives a new systems level picture of human cells under microgravity, generates testable hypothesis and may help estimating risk and developing medicine for space missions. PMID- 27185416 TI - Reducing emissions from agriculture to meet the 2 degrees C target. AB - More than 100 countries pledged to reduce agricultural greenhouse gas (GHG) emissions in the 2015 Paris Agreement of the United Nations Framework Convention on Climate Change. Yet technical information about how much mitigation is needed in the sector vs. how much is feasible remains poor. We identify a preliminary global target for reducing emissions from agriculture of ~1 GtCO2 e yr-1 by 2030 to limit warming in 2100 to 2 degrees C above pre-industrial levels. Yet plausible agricultural development pathways with mitigation cobenefits deliver only 21-40% of needed mitigation. The target indicates that more transformative technical and policy options will be needed, such as methane inhibitors and finance for new practices. A more comprehensive target for the 2 degrees C limit should be developed to include soil carbon and agriculture-related mitigation options. Excluding agricultural emissions from mitigation targets and plans will increase the cost of mitigation in other sectors or reduce the feasibility of meeting the 2 degrees C limit. PMID- 27185419 TI - The Gluten-Free Diet: Recognizing Fact, Fiction, and Fad. PMID- 27185418 TI - A combination of quantitative marinating and Maillard reaction to enhance volatile flavor in Chinese marinated chicken. AB - BACKGROUND: A combination of quantitative marinating and Maillard reaction was investigated by adding d-xylose, l-cysteine and thiamine to the marinated brine of quantitative marinating, which was expected to enhance the volatile flavor of Chinese marinated chicken. Response surface methodology was used to optimize parameters, in which response was sensory evaluation scores of marinated chicken. A Box-Behnken center design was applied to the optimized added contents. The optimized contents were d-xylose (1-50/00), l-cysteine (1-50/00) and thiamine (1 30/00). RESULTS: Analysis of variance indicated that a second-order polynomial equation could predict the experimental data well (R2 = 0.94), and sensory evaluation scores were significantly affected by the added amount of d-xylose, l cysteine and thiamine. The optimal conditions that maximized the sensory evaluation score of Chinese marinated chicken were found to be 4.960/00 d-xylose, 2.280/00 l-cysteine and 2.660/00 thiamine (w/w). Given these optimal conditions, a number of meat-like flavor compounds such as 2-pentyl-furan, benzothiazole and 4-methyl-5-thiazoleethanol were identified by gas chromatographic-mass spectrometric analysis. CONCLUSION: Our results suggested that a combination of quantitative marinating and Maillard reaction might be a promising method to enhance the volatile flavor, especially meat-like flavor, of Chinese marinated chicken. (c) 2016 Society of Chemical Industry. PMID- 27185420 TI - External dilator-assisted banding for high-flow hemodialysis arteriovenous fistula. AB - Creation of arteriovenous fistula (AVF) may lead to left ventricle hypertrophy and predispose for development or worsening of heart failure. It was postulated to reduce access blood flow if exceeded 2 L/min or cardiac index was higher than 3.0 L/min/m(2). Numbers of techniques decreasing flow were described. The major disadvantage was the complexity of procedure and necessity of intraoperative flow measurement needed to establish desired flow. The technique of dilator-assisted banding with no endovascular catheterization is presented. After blunt dissection non absorbable thread was placed around vessel and tied over the dilator. Then the dilator was gently removed and blood flow was confirmed by palpation. We performed 12 banding procedures. Mean brachial blood flows were 3733.2 +/- 826.2 mL/min preoperatively and 1461.2 +/- 337.7 mL/min after surgery. Mean flow reduction was 2272.2 +/- 726.9 mL/min. The external dilator-assisted banding is a feasible method for vascular access flow reduction without necessity of endovascular catheterization. PMID- 27185421 TI - Allergic contact dermatitis: Patient diagnosis and evaluation. AB - Allergic contact dermatitis resulting from exposure to a chemical or chemicals is a common diagnosis in the dermatologist's office. We are exposed to hundreds of potential allergens daily. Patch testing is the criterion standard for diagnosing the causative allergens responsible for allergic contact dermatitis. Patch testing beyond standard trays is often needed to fully diagnose patients, but not all dermatology practices have access to this testing procedure or these allergens. In order to adequately evaluate patients, physicians must understand the pathophysiology of the disease process and be well versed in the proper evaluation of patients, indications for patch testing, proper testing procedure, and other diagnostic tools available and be aware of new and emerging allergens. PMID- 27185422 TI - Allergic contact dermatitis: Patient management and education. AB - Allergic contact dermatitis is a common diagnosis resulting from exposure to a chemical or chemicals in a patient's personal care products, home, or work environment. Once patch testing has been performed, the education and management process begins. After the causative allergens have been identified, patient education is critical to the proper treatment and management of the patient. This must occur if the dermatitis is to resolve. Detailed education is imperative, and several resources are highlighted. Photoallergic contact dermatitis and occupational contact dermatitis are other considerations a clinician must keep in mind. PMID- 27185423 TI - Assessing the clinical effectiveness of an algorithmic approach for mucosal lichen planus (MLP): A retrospective review. AB - BACKGROUND: Mucosal lichen planus (MLP) is a therapeutic challenge in need of a new treatment approach because of its debilitating effect on patient's quality of life. OBJECTIVE: We sought to evaluate a standardized treatment plan for patients with MLP. A second objective was to describe the effect of mycophenolate mofetil in this patient population. METHODS: The study retrospectively analyzed 53 patients with MLP treated using a standardized algorithm. The number of MLP lesions, disease activity, and pain at the last visit were compared with baseline scores determined at the initial visit. Results were analyzed using the paired samples t test and confirmed with the Wilcoxon matched pairs signed rank test. RESULTS: The average number of lesions was reduced from 3.77 to 1.67 (P < .001). The average disease activity was reduced from 2.73 to 0.90 (P < .001). Average pain reported decreased from 2.03 to 1.03 (P < .001). LIMITATIONS: This study was a retrospective analysis of a small patient population. There was no universal symptom severity scale used at the time of treatment for some patients. CONCLUSION: The standardized treatment plan reduced symptoms for patients with MLP. Mycophenolate mofetil appears to be a reasonable treatment option for these patients. PMID- 27185425 TI - Lenalidomide for refractory chronic and subacute cutaneous lupus erythematosus: 16 patients. PMID- 27185424 TI - Time to local recurrence of lentigo maligna: Implications for future studies. PMID- 27185426 TI - Topical minocycline foam for moderate to severe acne vulgaris: Phase 2 randomized double-blind, vehicle-controlled study results. PMID- 27185427 TI - Use of topical retinoids by dermatologists and non-dermatologists in the management of acne vulgaris. PMID- 27185429 TI - Distance of travel to phototherapy is associated with early nonadherence: A retrospective cohort study. PMID- 27185428 TI - Thrombophilic status may predict prognosis in patients with metastatic BRAFV600 mutated melanoma who are receiving BRAF inhibitors. PMID- 27185430 TI - Clinicopathological and dermoscopic features of angio-eccrine hyperplasia in clear cell acanthoma. PMID- 27185431 TI - Lack of evidence that bedbugs transmit pathogens to humans. PMID- 27185432 TI - Enhancing the antiseptic properties of nonsterile disposable gloves: A prospective randomized pilot study of a novel sterilization technique for dermatologic surgery. PMID- 27185433 TI - Four-year experience with vismodegib hedgehog inhibitor therapy. PMID- 27185434 TI - Patient satisfaction in dermatologic care delivered by a medical-student-run free clinic. PMID- 27185435 TI - Clusters of CD123+ plasmacytoid dendritic cells help distinguish lupus alopecia from lichen planopilaris. PMID- 27185436 TI - Qualitative study shows disease damage matters to patients with hidradenitis suppurativa. PMID- 27185437 TI - Absence of skin cancer in the DNA repair-deficient disease Cockayne Syndrome (CS): A survey study. PMID- 27185438 TI - Characterization of patients with clinical overlap of morphea and systemic sclerosis: A case series. PMID- 27185439 TI - The effect of omalizumab dosing and frequency in chronic idiopathic urticaria: Retrospective chart review. PMID- 27185440 TI - The subunit method: A novel excisional approach for rhinophyma. PMID- 27185441 TI - Ex vivo high-frequency ultrasound: A novel proposal for management of surgical margins in patients with non-melanoma skin cancer. PMID- 27185442 TI - Utilizing the Patient Attitudes to Scarring Scale (PASS) to develop an outcome measure for postoperative scarring: A study in 430 patients. PMID- 27185443 TI - The dermatopathologist's role in genetic testing for hereditary cancer syndromes: Utility versus patient liberty. PMID- 27185444 TI - Plasmacytoid dendritic cells (pDCs) and regulatory T (Treg) cells may be the key to viral reactivation in drug-induced hypersensitivity syndrome (DIHS). PMID- 27185445 TI - Correction. PMID- 27185448 TI - The challenging diagnosis of eccrine poromas. PMID- 27185449 TI - Videodermoscopy enhances the ability to diagnose Kaposi's sarcoma by revealing its vascular structures. PMID- 27185450 TI - Dermoscopy of dermatofibrosarcoma protuberans on black skin. PMID- 27185452 TI - The selfie skin examination. PMID- 27185451 TI - Tinea nigra dermoscopy: A useful assessment. PMID- 27185454 TI - Assembling disposable punches using a shaving blade and hypodermic needle. PMID- 27185453 TI - Undermining the opposition: Ballistic tips for improving the island pedicle flap. PMID- 27185455 TI - Sterile adhesive tape: A useful adjunct when applying full-thickness skin grafts. PMID- 27185456 TI - Tips and Tricks: Single-Site Robotic-Assisted Myomectomy. AB - STUDY OBJECTIVE: To describe some tips and tricks that facilitate a single-site robotic- assisted (RA) myomectomy. DESIGN: Stepwise surgical tutorial using a narrated video (Canadian Task Force classification III). SETTING: Academic tertiary care hospital. INTERVENTIONS: Single-incision RA myomectomy is a novel technique that presents unique surgical challenges. Although similar in outcomes to multiport myomectomy, single-site myomectomy is more cosmetically appealing. Traditional laparoscopic single- site myomectomy has been associated with a steep learning curve. The robotic single-site platform mitigates some of these difficulties, which allows for the reproducibility and safety of this technique in appropriately selected patients. In this surgical tutorial, we present a case of a 7-cm type 2-5 fibroid removed with this approach. CONCLUSION: Single-site RA myomectomy is a safe, minimally invasive option for appropriately selected patients. Although it is a challenging procedure, it provides excellent cosmesis and is reproducible with adequate training and expertise. PMID- 27185457 TI - Exercise and sports science Australia (ESSA) position statement on exercise and spinal cord injury. AB - Traumatic spinal cord injury (SCI) may result in tetraplegia (motor and/or sensory nervous system impairment of the arms, trunk and legs) or paraplegia (motor and/or sensory impairment of the trunk and/or legs only). The adverse effects of SCI on health, fitness and functioning are frequently compounded by profoundly sedentary behaviour. People with paraplegia (PP) and tetraplegia (TP) have reduced exercise capacity due to paralysis/paresis and reduced exercising stroke volume. TP often further reduces exercise capacity due to lower maximum heart-rate and respiratory function. There is strong, consistent evidence that exercise can improve cardiorespiratory fitness and muscular strength in people with SCI. There is emerging evidence for a range of other exercise benefits, including reduced risk of cardio-metabolic disease, depression and shoulder pain, as well as improved respiratory function, quality-of-life and functional independence. Exercise recommendations for people with SCI are: >=30min of moderate aerobic exercise on >=5d/week or >=20min of vigorous aerobic >=3d/week; strength training on >=2d/week, including scapula stabilisers and posterior shoulder girdle; and >=2d/week flexibility training, including shoulder internal and external rotators. These recommendations may be aspirational for profoundly inactive clients and stratification into "beginning", "intermediate" and "advanced" will assist application of the recommendations in clinical practice. Flexibility exercise is recommended to preserve upper limb function but may not prevent contracture. For people with TP, Rating of Perceived Exertion may provide a more valid indication of exercise intensity than heart rate. The safety and effectiveness of exercise interventions can be enhanced by initial screening for autonomic dysreflexia, orthostatic hypotension, exercise-induced hypotension, thermoregulatory dysfunction, pressure sores, spasticity and pain. PMID- 27185458 TI - Clinical practice considerations in facioscapulohumeral muscular dystrophy Sydney, Australia, 21 September 2015. PMID- 27185459 TI - A cross sectional study of two independent cohorts identifies serum biomarkers for facioscapulohumeral muscular dystrophy (FSHD). AB - Measuring the severity and progression of facioscapulohumeral muscular dystrophy (FSHD) is particularly challenging because muscle weakness progresses over long periods of time and can be sporadic. Biomarkers are essential for measuring disease burden and testing treatment strategies. We utilized the sensitive, specific, high-throughput SomaLogic proteomics platform of 1129 proteins to identify proteins with levels that correlate with FSHD severity in a cross sectional study of two independent cohorts. We discovered biomarkers that correlate with clinical severity and disease burden measured by magnetic resonance imaging. Sixty-eight proteins in the Rochester cohort (n = 48) and 51 proteins in the Seattle cohort (n = 30) had significantly different levels in FSHD-affected individuals when compared with controls (p-value <= .005). A subset of these varied by at least 1.5 fold and four biomarkers were significantly elevated in both cohorts. Levels of creatine kinase MM and MB isoforms, carbonic anhydrase III, and troponin I type 2 reliably predicted the disease state and correlated with disease severity. Other novel biomarkers were also discovered that may reveal mechanisms of disease pathology. Assessing the levels of these biomarkers during clinical trials may add significance to other measures of quantifying disease progression or regression. PMID- 27185461 TI - The Nutrient-Dependent O-GlcNAc Modification Controls the Expression of Liver Fatty Acid Synthase. AB - Liver Fatty Acid Synthase (FAS) is pivotal for de novo lipogenesis. Loss of control of this metabolic pathway contributes to the development of liver pathologies ranging from steatosis to nonalcoholic steatohepatitis (NASH) which can lead to cirrhosis and, less frequently, to hepatocellular carcinoma. Therefore, deciphering the molecular mechanisms governing the expression and function of key enzymes such as FAS is crucial. Herein, we link the availability of this lipogenic enzyme to the nutrient-dependent post-translational modification O-GlcNAc that is thought to be deregulated in metabolic diseases (diabetes, obesity, and metabolic syndrome). We demonstrate that expression and activity of liver FAS correlate with O-GlcNAcylation contents in ob/ob mice and in mice fed with a high-carbohydrate diet both in a transcription-dependent and independent manner. More importantly, inhibiting the removal of O-GlcNAc residues in mice intraperitoneally injected with the selective and potent O-GlcNAcase (OGA) inhibitor Thiamet-G increases FAS expression. FAS and O-GlcNAc transferase (OGT) physically interact, and FAS is O-GlcNAc modified. Treatment of a liver cell line with drugs or nutrients that elevate the O-GlcNAcylation interferes with FAS expression. Inhibition of OGA increases the interaction between FAS and the deubiquitinase Ubiquitin-specific protease-2a (USP2A) in vivo and ex vivo, providing mechanistic insights into the control of FAS expression through O GlcNAcylation. Together, these results reveal a new type of regulation of FAS, linked to O-GlcNAcylation status, and advance our knowledge on deregulation of lipogenesis in diverse forms of liver diseases. PMID- 27185462 TI - A Robust Cu(OH)2 Nanoneedles Mesh with Tunable Wettability for Nonaqueous Multiphase Liquid Separation. AB - The separation of organic liquid mixtures is achieved by Cu(OH)2 nanoneedle covered copper mesh based on the difference of the liquid surface tension. The as prepared membrane allows the penetration of organic liquid with smaller surface tension and blocks the higher. Thus, the effective separation of these two organic liquids can be achieved. PMID- 27185463 TI - Surgical treatments for osteoarthritis. AB - There are two main surgical treatments for osteoarthritis: conservative treatments, where the damaged cartilage is left in place, and radical treatments, where the cartilage is replaced by an artificial endoprosthesis; this latter procedure is termed joint arthroplasty. These treatments are only offered to symptomatic patients. Arthrodesis is yet another surgical intervention in cases of osteoarthritis. It will sacrifice the joint's articular function and is performed on small osteoarthritic joints, such as wrists and ankles, for instance. Osteoarthritis symptoms are usually the consequence of an imbalance between the load applied to a joint and the surface available to support that load. Therefore, conservative treatments will either tend to decrease the load exerted on the joint, such as in a tibial valgus osteotomy for instance, or to improve the articular surface supporting that load. Sometimes, both can be provided at the same time; the peri-acetabular osteotomy for hip dysplasia is an example of such a procedure. Conservative treatments are usually offered to young patients in order to delay, if not avoid, the need for a joint prosthesis. They are usually performed before osteoarthritis appears or at an early stage. Joint arthroplasties have overwhelmingly excellent functional results and today's research is directed towards providing rapid recovery, very long-term stability, and the assurance of a good functionality in extreme conditions. However, complications with joint arthroplasties can be serious with little, if any, reasonable salvage solution. Therefore, these procedures are offered to patients who have failed adequate medical treatment measures. PMID- 27185465 TI - Automated microseismic event location using Master-Event Waveform Stacking. AB - Accurate and automated locations of microseismic events are desirable for many seismological and industrial applications. The analysis of microseismicity is particularly challenging because of weak seismic signals with low signal-to-noise ratio. Traditional location approaches rely on automated picking, based on individual seismograms, and make no use of the coherency information between signals at different stations. This strong limitation has been overcome by full waveform location methods, which exploit the coherency of waveforms at different stations and improve the location robustness even in presence of noise. However, the performance of these methods strongly depend on the accuracy of the adopted velocity model, which is often quite rough; inaccurate models result in large location errors. We present an improved waveform stacking location method based on source-specific station corrections. Our method inherits the advantages of full-waveform location methods while strongly mitigating the dependency on the accuracy of the velocity model. With this approach the influence of an inaccurate velocity model on the results is restricted to the estimation of travel times solely within the seismogenic volume, but not for the entire source-receiver path. We finally successfully applied our new method to a realistic synthetic dataset as well as real data. PMID- 27185460 TI - The Spliceosomal Protein SF3B5 is a Novel Component of Drosophila SAGA that Functions in Gene Expression Independent of Splicing. AB - The interaction between splicing factors and the transcriptional machinery provides an intriguing link between the coupled processes of transcription and splicing. Here, we show that the two components of the SF3B complex, SF3B3 and SF3B5, that form part of the U2 small nuclear ribonucleoprotein particle (snRNP) are also subunits of the Spt-Ada-Gcn5 acetyltransferase (SAGA) transcriptional coactivator complex in Drosophila melanogaster. Whereas SF3B3 had previously been identified as a human SAGA subunit, SF3B5 had not been identified as a component of SAGA in any species. We show that SF3B3 and SF3B5 bind to SAGA independent of RNA and interact with multiple SAGA subunits including Sgf29 and Spt7 in a yeast two-hybrid assay. Through analysis of sf3b5 mutant flies, we show that SF3B5 is necessary for proper development and cell viability but not for histone acetylation. Although SF3B5 does not appear to function in SAGA's histone modifying activities, SF3B5 is still required for expression of a subset of SAGA regulated genes independent of splicing. Thus, our data support an independent function of SF3B5 in SAGA's transcription coactivator activity that is separate from its role in splicing. PMID- 27185464 TI - Differential investment in visual and olfactory brain areas reflects behavioural choices in hawk moths. AB - Nervous tissue is one of the most metabolically expensive animal tissues, thus evolutionary investments that result in enlarged brain regions should also result in improved behavioural performance. Indeed, large-scale comparative studies in vertebrates and invertebrates have successfully linked differences in brain anatomy to differences in ecology and behaviour, but their precision can be limited by the detail of the anatomical measurements, or by only measuring behaviour indirectly. Therefore, detailed case studies are valuable complements to these investigations, and have provided important evidence linking brain structure to function in a range of higher-order behavioural traits, such as foraging experience or aggressive behaviour. Here, we show that differences in the size of both lower and higher-order sensory brain areas reflect differences in the relative importance of these senses in the foraging choices of hawk moths, as suggested by previous anatomical work in Lepidopterans. To this end we combined anatomical and behavioural quantifications of the relative importance of vision and olfaction in two closely related hawk moth species. We conclude that differences in sensory brain volume in these hawk moths can indeed be interpreted as differences in the importance of these senses for the animal's behaviour. PMID- 27185467 TI - Postnatal care: increasing coverage, equity, and quality. PMID- 27185466 TI - Molecular determinants of plaque size as an indicator of dengue virus attenuation. AB - The development of live viral vaccines relies on empirically derived phenotypic criteria, especially small plaque sizes, to indicate attenuation. However, while some candidate vaccines successfully translated into licensed applications, others have failed safety trials, placing vaccine development on a hit-or-miss trajectory. We examined the determinants of small plaque phenotype in two dengue virus (DENV) vaccine candidates, DENV-3 PGMK30FRhL3, which produced acute febrile illness in vaccine recipients, and DENV-2 PDK53, which has a good clinical safety profile. The reasons behind the failure of PGMK30FRhL3 during phase 1 clinical trial, despite meeting the empirically derived criteria of attenuation, have never been systematically investigated. Using in vitro, in vivo and functional genomics approaches, we examined infections by the vaccine and wild-type DENVs, in order to ascertain the different determinants of plaque size. We show that PGMK30FRhL3 produces small plaques on BHK-21 cells due to its slow in vitro growth rate. In contrast, PDK53 replicates rapidly, but is unable to evade antiviral responses that constrain its spread hence also giving rise to small plaques. Therefore, at least two different molecular mechanisms govern the plaque phenotype; determining which mechanism operates to constrain plaque size may be more informative on the safety of live-attenuated vaccines. PMID- 27185468 TI - Tracking perioperative mortality and maternal mortality: challenges and opportunities. PMID- 27185469 TI - Health of female sex workers and their children: a call for action. PMID- 27185470 TI - Pregnancy-associated plasma protein A (PAPP-A) to predict adverse fetal outcomes in Chinese: What is the optimal cutoff value? AB - A low level of PAPP-A predicts adverse fetal outcomes. As Chinese pregnant women have a higher level of PAPP-A, the predictive performance of PAPP-A and its optimal cutoff value might be different. This study aims to establish a PAPP-A cutoff value in the Chinese population that identifies adverse fetal outcomes. We retrospectively analysed 4936 spontaneous singleton pregnancies of Chinese women who underwent first-trimester combined Down's screening in our unit from March 2010 to January 2014 and had delivery information available. A composite adverse fetal outcome encompassed intrauterine fetal loss (including miscarriages and stillbirths), and live births either before 32 weeks or weighing less than -2 standard deviation (SD) for gestation. The area under the curve of the receiver operator characteristic curve for prediction of the composite adverse outcome using PAPP-A was 0.626 (95% CI =0.612-0.640, p < 0.0001). PAPP-A <= 0.23 multiples of median (MoM) identified 0.6% of Chinese pregnant women to be at significant risk of adverse fetal outcome (positive likelihood ratio 11.2, positive predictive value 21.4%) despite a low sensitivity (5.1%, 95% CI =1.9 10.8). The negative predictive value was high (97.7%). The commonly used cutoff of 0.4 MoM was associated with a positive likelihood ratio of 3.7 only. A prospective study is warranted. PMID- 27185472 TI - A science for all reasons: A comment on Ogden (2016). PMID- 27185471 TI - Human NK cells: From surface receptors to clinical applications. AB - Natural killer (NK) cells play a major role in innate defenses against pathogens, primarily viruses, and are also thought to be part of the immunosurveillance against tumors. They express an array of surface receptors that mediate NK cell function. The human leukocytes antigen (HLA) class I-specific inhibitory receptors allow NK cells to detect and kill cells that have lost or under-express HLA class I antigens, a typical feature of tumor or virally infected cells. However, NK cell activation and induction of cytolytic activity and cytokine production depends on another important checkpoint, namely the expression on target cells of ligands recognized by activating NK receptors. Despite their potent cytolytic activity, NK cells frequently fail to eliminate tumors. This is due to mechanisms of tumor escape, determined by the tumor cells themselves or by tumor-associated cells (i.e. the tumor microenvironment) via the release of soluble suppressive factors or the induction of inhibitory loops involving induction of regulatory T cells, M2-polarized macrophages and myeloid-derived suppressor cells. The most important clinical application involving NK cells is the cure of high-risk leukemias in the haplo-identical hematopoietic stem cell transplant (HSCT) setting. NK cells originated from hematopoietic stem cells (HSC) of HLA-haploidentical donors may express Killer Immunoglobulin-like receptors (KIRs) that are mismatched with the HLA class I alleles of the recipient. This allows NK cells to kill leukemia blasts residual after the conditioning regimen, while sparing normal cells (that do not express ligands for activating NK receptors). More recent approaches based on the specific removal of TCR alpha/beta(+) T cells and of CD19(+) B cells, allow the infusion, together with CD34(+) HSC, of mature KIR(+) NK cells and of TCR gamma/delta(+) T cells, both characterized by a potent anti-leukemia activity. This greatly reduces the time interval necessary to obtain alloreactive, KIR(+) NK cells derived from donor HSC. Another promising approach is based on the use of anti-KIR blocking monoclonal antibodies (mAbs), rendering alloreactive any KIR(+) NK cells. PMID- 27185476 TI - TDE Adopts the Standards for Quality Improvement Reporting Excellence (SQUIRE) Guidelines. PMID- 27185473 TI - Altered metabolite accumulation in tomato fruits by coexpressing a feedback insensitive AroG and the PhODO1 MYB-type transcription factor. AB - Targeted manipulation of phenylalanine (Phe) synthesis is a potentially powerful strategy to boost biologically and economically important metabolites, including phenylpropanoids, aromatic volatiles and other specialized plant metabolites. Here, we use two transgenes to significantly increase the levels of aromatic amino acids, tomato flavour-associated volatiles and antioxidant phenylpropanoids. Overexpression of the petunia MYB transcript factor, ODORANT1 (ODO1), combined with expression of a feedback-insensitive E. coli 3-deoxy-D arabino-heptulosonate 7-phosphate synthase (AroG), altered the levels of multiple primary and secondary metabolites in tomato fruit, boosting levels of multiple secondary metabolites. Our results indicate that coexpression of AroG and ODO1 has a dual effect on Phe and related biosynthetic pathways: (i) positively impacting tyrosine (Tyr) and antioxidant related metabolites, including ones derived from coumaric acid and ferulic acid; (ii) negatively impacting other downstream secondary metabolites of the Phe pathway, including kaempferol-, naringenin- and quercetin-derived metabolites, as well as aromatic volatiles. The metabolite profiles were distinct from those obtained with either single transgene. In addition to providing fruits that are increased in flavour and nutritional chemicals, coexpression of the two genes provides insights into regulation of branches of phenylpropanoid metabolic pathways. PMID- 27185474 TI - A novel gene mutation in PANK2 in a patient with severe jaw-opening dystonia. AB - Pantothenate kinase-associated neurodegeneration (PKAN) is a rare neurodegenerative condition. Major clinical features include progressive dystonia, pigmentary retinopathy, spasticity, and cognitive decline. The typical MRI sign of the disease, known as "eye-of-the-tiger", is what makes differential diagnosis possible. We here describe a 16-year-old male patient with PKAN presenting with severe and sustained jaw-opening dystonia which may be due to heterogeneous etiologies showing poor response to treatment. Herein, long-term follow-up and genetic results of a PKAN case who experienced severe jaw-opening dystonia are presented and discussed. PMID- 27185477 TI - In vitro sensitivity of different activated partial thromboplastin time reagents to mild clotting factor deficiencies. AB - INTRODUCTION: Activated partial thromboplastin time (aPTT) is a routine clotting assay that is widely used to globally screen for coagulation abnormalities. It is commonly admitted that a prolonged test result, may trigger the need for specific assays to be performed, particularly factor measurement. However, the sensitivity of aPTT reagents to deficiencies of clotting factors varies. METHODS: We evaluated, according to the recommendation of the CLSI H47-A2 guideline, the responsiveness to single factor levels of five aPTT reagents by using factor deficient plasmas spiked with a calibration plasma to produce individual factor activities ranging from <1 to ~100 Unit (U)/dL. Test results were expressed as the sample-to-control ratio, the latter was defined as the clotting time obtained in the calibration plasma containing ~100 U/dL factor activity. The factor activity producing a prolongation of aPTT above the upper limit of its specific normal range (in ratio) was assigned as the factor responsiveness in U/dL to that reagent. RESULTS: Responsiveness ranged from 34 to 47 U/dL to FVIII: C, from 18 to 57 U/dL to FIX, from 38 to 52 U/dL to FXI, from 29 to 50 U/dL to FXII, from 40 and 59 U/dL to FV, from 7.5 to 49 U/dL to FX, and from 9.1 to 10.5 U/dL to FII. CONCLUSIONS: These results suggest that the sensitivity of the tested aPTT reagents to single factor deficiency is highly variable. Moreover, for one given aPTT reagent, its sensitivity was very different depending on the deficient factor. This must be considered when analyzing clinical materials. PMID- 27185479 TI - Three-component oxysulfenylation reaction: two simple and convenient approaches to beta-alkoxy sulfides. AB - An unprecedented method for the synthesis of beta-alkoxy sulfides via a NaI/HBr mediated three-component oxysulfenylation reaction of alkenes with arylsulfinic acids and alcohols is reported. Furthermore, I2-promoted oxysulfenylation of alkenes using sodium arylsulfinates instead of arylsulfinic acids to synthesise various beta-alkoxy sulfides is also described. PMID- 27185478 TI - Investigation of bacterial inactivation in apheresis platelets with 24 or 30 hours between inoculation and inactivation. AB - BACKGROUND AND OBJECTIVES: Blood Centre logistics, staffing and donor scheduling may be optimized if pathogen inactivation (PI) of platelets can be delayed until Day 1, but bacteria may rapidly grow during this time. This study evaluates bacterial PI performed 24 and 30 h after collection. MATERIALS AND METHODS: PAS-3 platelet units were collected on the Amicus and subsequently inoculated (3-53 CFU/unit) with 1of 5 transfusion relevant bacterial species (n = 3/organism). Units were then stored for either 24 +/- 0.3 or 30 +/- 0.3 h at 20-24 degrees C with agitation, subsequently treated with amotosalen and UVA, and stored for 7 days. Samples were taken before and after inactivation, on Days 2, 5 and 7 for BacT/ALERT testing, and on Days 5 and 7 for plate counts. RESULTS: All samples from units taken prior to inactivation either demonstrated positive plate culture counts, or, in untreated positive controls, were culture-positive during storage. All contaminated units treated with amotosalen and UVA 24 after inoculation were culture-negative on all days tested. With inactivation performed 30 h following inoculation, one of 15 units (1-of-3 replicates) was culture-positive with Klebsiella pneumonia (1 * 109 CFU/ml) by Day 5. CONCLUSION: Photochemical treatment did not inactivate 1 of 15 units to sterility in apheresis platelets stored in PAS with a 30-h delay between contamination and treatment, but did inactivate 15 of 15 units with a 24-h delay. PMID- 27185481 TI - Pregnant and peripartum women are not at increased risk for psychotic experiences at the population level: Evidence from 46 countries. PMID- 27185482 TI - Dissecting negative symptoms of schizophrenia: History, assessment, pathophysiological mechanisms and treatment. PMID- 27185483 TI - Clinical and biological correlates of resilience in patients with schizophrenia and bipolar disorder: A cross-sectional study. AB - OBJECTIVE: The concept of resilience is relevant in understanding the heterogeneous outcomes noted in schizophrenia and bipolar disorder. However, clinical and biological correlates of resilience in these populations have rarely been investigated. We aimed to identify key correlates of subjective resilience in such patients using comprehensive assessments and to explore associations between resilience levels and peripheral biomarkers. METHOD: 180 subjects with DSM-IV schizophrenia, bipolar disorder, and healthy controls (60 per group) were included. Demographic and clinical variables were assessed by means of interview and various psychometric scales. Furthermore, blood and saliva samples were obtained for the assessment of brain-derived neurotrophic factor, adrenocorticotropic hormone, cortisol, high sensitivity C-reactive protein, and alpha-amylase levels. Cross-sectional associations with resilience, as assessed by the 25-item Resilience Scale were sought. RESULTS: Resilience Scale total scores were significantly higher in healthy individuals (130.1, 95% confidence intervals (CI): 124.8-135.4) compared to subjects with schizophrenia (109.9, 95% CI: 104.6-115.2, p<0.001) and bipolar disorder (119.0, 95% CI: 113.8-124.3, p=0.012), while the difference between patient groups was non-significant (p=0.055). Self-esteem, spirituality, quality of life, and hopelessness were correlated with resilience in all three groups. In addition, internalized stigma and depression were relevant factors in the schizophrenia and bipolar disorder group, respectively. Correlations between resilience levels and peripheral biomarkers did not reach significance. CONCLUSION: Although causal relationships must be confirmed in prospective studies, our results have implications in developing psychological interventions to enhance resilience in patients with schizophrenia and bipolar disorder. The biological correlates of resilience in these populations warrant further investigations. PMID- 27185484 TI - Developmental exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin may alter LH release patterns by abolishing sex differences in GABA/glutamate cell number and modifying the transcriptome of the male anteroventral periventricular nucleus. AB - Developmental exposure to arylhydrocarbon receptor (AhR) ligands abolishes sex differences in a wide range of neural structures and functions. A well-studied example is the anteroventral periventricular nucleus (AVPV), a structure that controls sex-specific luteinizing hormone (LH) release. In the male, testosterone (T) secreted by the developing testes defeminizes LH release mechanisms; conversely, perinatal AhR activation by 2,3,7,8,-tetrachlorodibenzo-p-dioxin (TCDD) blocks defeminization. To better understand developmental mechanisms altered by TCDD exposure, we first verified that neonatal TCDD exposure in male rats prevented the loss of AVPV GABA/glutamate neurons that are critical for female-typical LH surge release. We then used whole genome arrays and quantitative real-time polymerase chain reaction (QPCR) to compare AVPV transcriptomes of males treated neonatally with TCDD or vehicle. Our bioinformatics analyses showed that TCDD enriched gene sets important for neuron development, synaptic transmission, ion homeostasis, and cholesterol biosynthesis. In addition, upstream regulatory analysis suggests that both estrogen receptors (ER) and androgen receptors (AR) regulate genes targeted by TCDD. Of the 23 mRNAs found to be changed by TCDD at least 2-fold (p<0.05), most participate in the functions identified in our bioinformatics analyses. Several, including matrix metallopeptidase 9 and SRY-box 11 (Sox11), are known targets of E2. CUG triplet repeat, RNA binding protein 2 (cugbp2) is particularly interesting because it is sex-specific, oppositely regulated by estradiol (E2) and TCDD. Moreover, it regulates the post-transcriptional processing of molecules previously linked to sexual differentiation of the brain. These findings provide new insights into how TCDD may interfere with defeminization of LH release patterns. PMID- 27185485 TI - Lithium accelerates functional motor recovery by improving remyelination of regenerating axons following ventral root avulsion and reimplantation. AB - Brachial plexus injury (BPI) often involves the complete or partial avulsion of one or more of the cervical nerve roots, which leads to permanent paralysis of the innervated muscles. Reimplantation surgery has been attempted as a clinical treatment for brachial plexus root avulsion but has failed to achieve complete functional recovery. Lithium is a mood stabilizer drug that is used to treat bipolar disorder; however, its effects on spinal cord or peripheral nerve injuries have also been reported. The purpose of this study was to investigate whether lithium can improve functional motor recovery after ventral root avulsion and reimplantation in a rat model of BPI. The results showed that systemic treatment with a clinical dose of lithium promoted motor neuron outgrowth and increased the efficiency of motor unit regeneration through enhanced remyelination. An analysis of myelin-associated genes showed that the effects of lithium started during the early phase of remyelination and persisted through the late stage of the process. Efficient remyelination of the regenerated axons in the lithium-treated rats led to an earlier functional recovery. Therefore, we demonstrated that lithium might be a potential clinical treatment for BPI in combination with reimplantation surgery. PMID- 27185487 TI - Regionally distinct phasic dopamine release patterns in the striatum during reversal learning. AB - Striatal dopamine (DA) plays a central role in reward-related learning and behavioral adaptation to changing environments. Recent studies suggest that rather than being broadcast as a uniform signal throughout the entire region, DA release dynamics diverge between different striatal regions. In a previous study, we showed that phasic DA release patterns in the ventromedial striatum (VMS) rapidly adapt during reversal learning. However, it is unknown how DA dynamics in the dorsolateral striatum (DLS) are modulated during such adaptive behavior. Here, we used fast-scan cyclic voltammetry to measure phasic DA release in the DLS during spatial reversal learning. In the DLS, we observed minor DA release after the onset of a visual cue signaling reward availability, followed by more pronounced DA release during more proximal reward cues (e.g., lever extension) and execution of the operant response (i.e., lever press), both in rewarded and non-rewarded trials. These release dynamics (minor DA after onset of the predictive visual cue, prominent DA during the operant response) did not change significantly during or following a reversal of response-reward contingencies. Notably, the DA increase to the lever press did not reflect a general signal related to the initiation of any motivated motor response, as we did not observe DA release when rats initiated nose pokes into the food receptacle during inter trial intervals. This suggests that DA release in the DLS occurs selectively during the initiation and execution of a learned operant response. Together with our previous results obtained in the VMS, these findings reveal distinct phasic DA release patterns during adaptation of established behavior in DLS and VMS. The VMS DA signal, which is highly sensitive to reversal of response-reward contingences, may provide a teaching signal to guide reward-related learning and facilitate behavioral adaptation, whereas DLS DA may reflect a 'response execution signal' largely independent of outcome, that may be involved in initiation and energizing of operant behavior. PMID- 27185488 TI - Effects of acetylated wood powder on growth performance, hepatic and muscular free amino acid profiles, and inosine 5'-monophosphate concentration of breast meat in broiler chickens. AB - The present study was conducted to determine the effects of acetylated wood powder (AW) as a new feed additive on performance, liver and muscle metabolism of amino acids and fatty acids and nucleotide-related substances of meat in broiler chickens. It was hypothesised that acetic acid desorbed from AW during intestinal digestion affects tissue metabolism. Two-week-old broiler chicks were divided into four groups and fed on diets supplemented with wood powder (30 g/kg) less than 106 um in diameter, except for controls. The AW was added to diets at 0, 10 and 30 g/kg to replace the non-acetylated wood powder (NAW) for 26 d. Plasma, liver tissue and breast muscle were taken from half of birds at 40 d of age under the fed condition. After the remaining chickens were fasted for 14 h, breast muscle was taken and refrigerated for 24 h. Consumption of wood powder with or without acetyl groups had no effect on growth performance including tissue weights of abdominal fat and breast muscle and plasma metabolites. Feeding AW decreased total free amino acid concentrations in the liver compared to the group only fed on the NAW. This response was dependent mainly on reduced non-essential and glucogenic amino acid concentrations. However, in breast muscle, alterations of free amino acid concentrations were observed only for histidine and tryptophan. In addition, the fatty acid composition of liver and breast muscle was not affected by feeding AW. In breast meat obtained from fasted chickens, the higher level of AW increased the concentration of inosine 5'-monophosphate, a taste-active compound, and in contrast, decreased the subsequent catabolites (inosine and hypoxanthine). However, the concentration of glutamic acid, a taste active compound, was lowered at this level of AW ingestion. Therefore, this study suggested that feeding AW as a new feed additive regulates ante-mortem amino acid utilisation in the liver and contributes to retard post-mortem degradation of inosine 5'-monophosphate as a taste-active compound in chicken meat. PMID- 27185486 TI - Immunostaining for Homer reveals the majority of excitatory synapses in laminae I III of the mouse spinal dorsal horn. AB - The spinal dorsal horn processes somatosensory information before conveying it to the brain. The neuronal organization of the dorsal horn is still poorly understood, although recent studies have defined several distinct populations among the interneurons, which account for most of its constituent neurons. All primary afferents, and the great majority of neurons in laminae I-III are glutamatergic, and a major factor limiting our understanding of the synaptic circuitry has been the difficulty in identifying glutamatergic synapses with light microscopy. Although there are numerous potential targets for antibodies, these are difficult to visualize with immunocytochemistry, because of protein cross-linking following tissue fixation. Although this can be overcome by antigen retrieval methods, these lead to difficulty in detecting other antigens. The aim of this study was to test whether the postsynaptic protein Homer can be used to reveal glutamatergic synapses in the dorsal horn. Immunostaining for Homer gave punctate labeling when viewed by confocal microscopy, and this was restricted to synapses at the ultrastructural level. We found that Homer puncta were colocalized with the AMPA receptor GluR2 subunit, but not with the inhibitory synapse-associated protein gephyrin. We also examined several populations of glutamatergic axons and found that most boutons were in contact with at least one Homer punctum. These results suggest that Homer antibodies can be used to reveal the great majority of glutamatergic synapses without antigen retrieval. This will be of considerable value in tracing synaptic circuits, and also in investigating plasticity of glutamatergic synapses in pain states. PMID- 27185489 TI - Long-term leucine supplementation aggravates prolonged strenuous exercise-induced cardiovascular changes in trained rats. AB - NEW FINDINGS: What is the central question of this study? Can long-term leucine supplementation prevent prolonged strenuous endurance exercise induced cardiac injury? What is the main finding and its importance? Prolonged endurance exercise does not seem to exceed cardiac energetic capacity, hence it does not represent an energy threat to this organ, at least in trained subjects. However, it may induce, in susceptible individuals, a state of cardiac electrical instability, which has been associated with ventricular arrhythmias and sudden cardiac death. This situation might be worsened when combined with leucine supplementation, which leads to increased blood pressure and cardiac injury. Leucine supplementation failed to prevent cardiac fatigue symptoms and may aggravate prolonged strenuous exercise-induced cardiovascular disturbances in trained rats. Observational studies have raised concerns that prolonged strenuous exercise training may be associated with increased risk of cardiac arrhythmia and even primary cardiac arrest or sudden death. It has been demonstrated that leucine can reduce prolonged exercise-induced muscle damage and accelerate the recovery process. The aim of this study was to investigate the effects of prolonged strenuous endurance exercise on cardiovascular parameters and biomarkers of cardiac injury in trained adult male rats and assess the use of leucine as an auxiliary substance to prevent the likely cardiac adverse effects caused by strenuous exercise. Twenty-four male Wistar rats were randomly allocated to receive a balanced control diet (18% protein) or a leucine-rich diet (15% protein plus 3% leucine) for 6 weeks. The rats were submitted to 1 h of exercise, 5 days per week for 6 weeks. Three days after the training period, the rats were submitted to swimming exercise until exhaustion, and cardiac parameters were assessed. Exercising until exhaustion significantly increased cardiac biomarker levels, cytokines and glycogen content inhibited protein synthesis signalling and led to cardiac electrical disturbances. When combined with exercise, leucine supplementation led to greater increases in the aforementioned parameters and also a significant increase in blood pressure and protein degradation signalling. We report, for the first time, that leucine supplementation not only fails to prevent cardiac fatigue symptoms, but may also aggravate prolonged strenuous exercise-induced cardiovascular disturbances in trained rats. Furthermore, we find that exercising until exhaustion can cause cardiac electrical disturbances and damage cardiac myocytes. PMID- 27185490 TI - Synthetic p55 tandem DNA vaccine against Pneumocystis carinii in rats. AB - Pneumocystis spp. are opportunistic fungal pathogens that are closely associated with severe pneumonia and pulmonary complications in patients with impaired immunity. In this study, the antigenic epitopes of the gene encoding the 55 kDa antigen fragment of Pneumocystis (p55), which may play an important role in Pneumocystis pneumonia, were analyzed. A gene containing tandem variants of the p55 antigen was synthesized and named the tandem antigen gene (TAG). TAG's potential as a DNA vaccine was assessed in immunosuppressed rats. Immunization with p55-TAG DNA vaccine significantly reduced both the pathogen burden and lung weight to body-weight ratios. Additionally, p55-TAG vaccination in immunosuppressed rats elicited both cell-mediated and humoral immunity. PMID- 27185491 TI - Advancing Migrant Access to Health Services in Europe (AMASE): Protocol for a Cross-sectional Study. AB - BACKGROUND: Migrants form a substantial proportion of the population affected by the human immunodeficiency virus (HIV) epidemic in Europe, yet HIV prevention for this population is hindered by poor understanding of access to care and of postmigration transmission dynamics. OBJECTIVE: We present the design and methods of the advancing Migrant Access to health Services in Europe (aMASE) study, the first European cross-cultural study focused on multiple migrant populations. It aims to identify the structural, cultural, and financial barriers to HIV prevention, diagnosis, and treatment and to determine the likely country of HIV acquisition in HIV-positive migrant populations. METHODS: We delivered 2 cross sectional electronic surveys across 10 countries (Belgium, France, Germany, Greece, Italy, the Netherlands, Portugal, Spain, Switzerland, and United Kingdom). A clinic survey aimed to recruit up to 2000 HIV-positive patients from 57 HIV clinics in 9 countries. A unique study number linked anonymized questionnaire data to clinical records data (viral loads, CD4 cell counts, viral clades, etc). This questionnaire was developed by expert panel consensus and cognitively tested, and a pilot study was carried out in 2 countries. A Web-based community survey (n=1000) reached those living with HIV but not currently accessing HIV clinics, as well as HIV-negative migrants. It was developed in close collaboration with a community advisory group (CAG) made up of representatives from community organizations in 9 of the participating countries. The CAG played a key role in data collection by promoting the survey to higher risk migrant groups (sub-Saharan Africans, Latin Americans, men who have sex with men, and people who inject drugs). The questionnaires have considerable content overlap, allowing for comparison. Questions cover ethnicity, migration, immigration status, HIV testing and treatment, health-seeking behavior, sexual risk, and drug use. The electronic questionnaires, which were available in 15 languages, allowed for complex routing, preventing respondents from answering irrelevant questions. RESULTS: In total, we recruited 2249 participants from 57 HIV clinics as part of the clinic survey and retrieved 1637 complete responses as part of the community survey. CONCLUSIONS: The findings will provide much-needed information for improving HIV prevention interventions and access to services for migrant communities. PMID- 27185493 TI - Nanometals for Solar-to-Chemical Energy Conversion: From Semiconductor-Based Photocatalysis to Plasmon-Mediated Photocatalysis and Photo-Thermocatalysis. AB - Nanometal materials play very important roles in solar-to-chemical energy conversion due to their unique catalytic and optical characteristics. They have found wide applications from semiconductor photocatalysis to rapidly growing surface plasmon-mediated heterogeneous catalysis. The recent research achievements of nanometals are reviewed here, with regard to applications in semiconductor photocatalysis, plasmonic photocatalysis, and plasmonic photo thermocatalysis. As the first important topic discussed here, the latest progress in the design of nanometal cocatalysts and their applications in semiconductor photocatalysis are introduced. Then, plasmonic photocatalysis and plasmonic photo thermocatalysis are discussed. A better understanding of electron-driven and temperature-driven catalytic behaviors over plasmonic nanometals is helpful to bridge the present gap between the communities of photocatalysis and conventional catalysis controlled by temperature. The objective here is to provide instructive information on how to take the advantages of the unique functions of nanometals in different types of catalytic processes to improve the efficiency of solar energy utilization for more practical artificial photosynthesis. PMID- 27185492 TI - Improved sensitivity of computed tomography towards iodine and gold nanoparticle contrast agents via iterative reconstruction methods. AB - Computed tomography is a widely used medical imaging technique that has high spatial and temporal resolution. Its weakness is its low sensitivity towards contrast media. Iterative reconstruction techniques (ITER) have recently become available, which provide reduced image noise compared with traditional filtered back-projection methods (FBP), which may allow the sensitivity of CT to be improved, however this effect has not been studied in detail. We scanned phantoms containing either an iodine contrast agent or gold nanoparticles. We used a range of tube voltages and currents. We performed reconstruction with FBP, ITER and a novel, iterative, modal-based reconstruction (IMR) algorithm. We found that noise decreased in an algorithm dependent manner (FBP > ITER > IMR) for every scan and that no differences were observed in attenuation rates of the agents. The contrast to noise ratio (CNR) of iodine was highest at 80 kV, whilst the CNR for gold was highest at 140 kV. The CNR of IMR images was almost tenfold higher than that of FBP images. Similar trends were found in dual energy images formed using these algorithms. In conclusion, IMR-based reconstruction techniques will allow contrast agents to be detected with greater sensitivity, and may allow lower contrast agent doses to be used. PMID- 27185494 TI - Investigation of Migration and Differentiation of Human Mesenchymal Stem Cells on Five-Layered Collagenous Electrospun Scaffold Mimicking Native Cartilage Structure. AB - Cartilage degeneration is the major cause of chronic pain, lost mobility, and reduced quality of life for over estimated 150 million osteoarthritis sufferers worldwide. Despite intensive research, none of the available therapies can restore the hyaline cartilage surface beyond just fibrous repair. To overcome these limitations, numerous cell-based approaches for cartilage repair are being explored that aim to provide an appropriate microenvironment for chondrocyte maintenance and differentiation of multipotent mesenchymal stem cells (MSCs) toward the chondrogenic lineage. Articular cartilage is composed of highly organized collagen network that entails the tissue into four distinct zones and each zone into three different regions based on differences in matrix morphology and biochemistry. Current cartilage implants cannot establish the hierarchical tissue organization that seems critical for normal cartilage function. Therefore, in this study, a structured, multilayered collagen scaffold designed for the replacement of damaged cartilage is presented that allows repopulation by host cells and synthesis of a new natural matrix. By using the electrospinning method, the potential to engineer a scaffold consisting of two different collagen types is obtained. With the developed collagen scaffold, a five-layered biomaterial is created that has the potency to induce the differentiation of human bone marrow derived MSCs toward the chondrogenic lineage. PMID- 27185495 TI - 15-deoxy prostaglandin J2, the nonenzymatic metabolite of prostaglandin D2, induces apoptosis in keratinocytes of human hair follicles: a possible explanation for prostaglandin D2-mediated inhibition of hair growth. AB - Recent studies have shown that prostaglandin D2 (PGD2) and its nonenzymatic metabolite, 15-deoxy-Delta(12,14)-prostaglandin J2 (15-dPGJ2), inhibit in vitro growth of explanted human hair follicles and inhibit hair growth in mice through the GPR44 (DP2). However, the underlying mechanism is still unclear. In this study, we first investigated the expression of DP2 in human hair follicles and in cultured follicular cells. We found that DP2 is strongly expressed in the outer root sheath (ORS) cells and weakly expressed in the dermal papilla (DP) cells. We observed slight growth stimulation when ORS and DP cells were treated with PGD2. We also observed slight growth stimulation when DP and ORS cells were treated with low concentrations (0.5 and 1 MUM) of 15-dPGJ2. However, 5 MUM 15-dPGJ2 inhibited the viability and caused apoptosis of both cell types. Exposure of cultured human hair follicles to 15-dPGJ2 resulted in significant apoptosis in follicular keratinocytes. Altogether, our data provide an evidence that 15-dPGJ2 promotes apoptosis in follicular keratinocytes and provide rationale for developing remedies for the prevention and treatment of hair loss based on DP2 antagonism. PMID- 27185497 TI - Seeing the invisible in differential interference contrast microscopy images. AB - Automated microscopy image restoration, especially in Differential Interference Contrast (DIC) imaging modality, has attracted increasing attentions since it greatly facilitates long-term living cell analysis without staining. Although the previous work on DIC image restoration is able to restore the nuclei regions of living cells, it is still challenging to reconstruct the unnoticeable cytoplasm details in DIC images. In this paper, we propose to extract the tiny movement information of living cells in DIC images and reveal the hidden details in DIC images by magnifying the cells' motion as well as attenuating the intensity variation from the background. From our restored images, we can clearly observe the previously-invisible details in DIC images. Experiments on two DIC image datasets show that the motion-based restoration method can reveal the hidden details of living cells. In addition, we demonstrate our restoration method can also be applied to other imaging modalities such as the phase contrast microscopy to enhance cells' details. Furthermore, based on the pixel-level restoration results, we can obtain the object-level segmentation by leveraging a label propagation approach, providing promising results on facilitating the cell shape and behavior analysis. The proposed algorithm can be a software module to enhance the visualization capability of microscopes. PMID- 27185496 TI - Contractile effects and receptor analysis of adenosine-receptors in human detrusor muscle from stable and neuropathic bladders. AB - To measure the relative transcription of adenosine receptor subtypes and the contractile effects of adenosine and selective receptor-subtype ligands on detrusor smooth muscle from patients with neuropathic overactive (NDO) and stable bladders and also from guinea-pigs. Contractile function was measured at 37 degrees C in vitro from detrusor smooth muscle strips. Contractions were elicited by superfusate agonists or by electrical field stimulation. Adenosine-receptor (A1, A2A, A2B, A3) transcription was measured by RT-PCR. Adenosine attenuated nerve-mediated responses with equivalent efficacy in human and guinea-pig tissue (pIC50 3.65-3.86); the action was more effective at low (1-8 Hz) compared to high (20-40 Hz) stimulation frequencies in human NDO and guinea-pig tissue. With guinea-pig detrusor the action of adenosine was mirrored by the A1/A2-agonist N ethylcarboxamidoadenosine (NECA), partly abolished in turn by the A2B-selectve antagonist alloxazine, as well as the A1-selective agonist N6- cyclopentyladenosine (CPA). With detrusor from stable human bladders the effects of NECA and CPA were much smaller than that of adenosine. Adenosine also attenuated carbachol contractures, but mirrored by NECA (in turn blocked by alloxazine) only in guinea-pig tissue. Adenosine receptor subtype transcription was measured in human detrusor and was similar in both groups, except reduced A2A levels in overactive bladder. Suppression of the carbachol contracture in human detrusor is independent of A-receptor activation, in contrast to an A2B-dependent action with guinea-pig tissue. Adenosine also reduced nerve-mediated contractions, by an A1- dependent action suppressing ATP neurotransmitter action. PMID- 27185498 TI - Steroid LC-MS has come of age. PMID- 27185499 TI - Stem cells and the role of ETS transcription factors in the differentiation hierarchy of normal and malignant prostate epithelium. AB - Prostate cancer is the most common cancer of men in the UK and accounts for a quarter of all new cases. Although treatment of localised cancer can be successful, there is no cure for patients presenting with invasive prostate cancer and there are less treatment options. They are generally treated with androgen-ablation therapies but eventually the tumours become hormone resistant and patients develop castration-resistant prostate cancer (CRPC) for which there are no further successful or curative treatments. This highlights the need for new treatment strategies. In order to prevent prostate cancer recurrence and treatment resistance, all the cell populations in a heterogeneous prostate tumour must be targeted, including the rare cancer stem cell (CSC) population. The ETS transcription factor family members are now recognised as a common feature in multiple cancers including prostate cancer; with aberrant expression, loss of tumour suppressor function, inactivating mutations and the formation of fusion genes observed. Most notably, the TMPRSS2-ERG gene fusion is present in approximately 50% of prostate cancers and in prostate CSCs. However, the role of other ETS transcription factors in prostate cancer is less well understood. This review will describe the prostate epithelial cell hierarchy and discuss the evidence behind prostate CSCs and their inherent resistance to conventional cancer therapies. The known and proposed roles of the ETS family of transcription factors in prostate epithelial cell differentiation and regulation of the CSC phenotype will be discussed, as well as how they might be targeted for therapy. PMID- 27185501 TI - Products with Natural Components to Heal Dermal Burns: A Patent Review. AB - BACKGROUND: Burns are a global public health problem, and non-fatal burn injuries are a leading cause of morbidity. The scale of the problem has led researchers to seek to develop new prod- ucts (both synthetic and natural) for use in the treatment of burn lesions. OBJECTIVE: The aim of this study was to examine all patents in databases between 2010 and 2015 related to natural prod- ucts for the treatment of burn-related wounds that targeted tissue repair and healing. METHOD: The search term "burn" and the code A61K36/00 (plant and other natural derivatives used in medicinal prepara- tions) from the international classification of patents were used to identify treatments. RESULTS: The search was performed in the WIPO, ESPACENET and USPTO databases. The highest number of patent ap- plications was found in the WIPO data base (617), followed by ESPACENET(23) and USPTO(6). The USA and China were the countries with the most patent applications, and 2008 was the year that had the highest number of applications. Patent applications written in Spanish, English and Portuguese and that were published between 2010 and 2015 were se- lected. 559 patent applications in other languages, and 63 that did not result in the creation of new products between 2010 and 2015 were excluded and the remaining 13 patents application were selected for full reading of the text. CONCLUSION: Through this study we were able to identify and summarize the new active natural compounds that can be used in the treatment of burns, both in terms of tissue recovery and analgesia. PMID- 27185502 TI - A Review of Gene Knockout Strategies for Microbial Cells. AB - BACKGROUND: Predicting the effects of genetic modification is difficult due to the complexity of metabolic net- works. Various gene knockout strategies have been utilised to deactivate specific genes in order to determine the effects of these genes on the function of microbes. Deactivation of genes can lead to deletion of certain proteins and functions. Through these strategies, the associated function of a deleted gene can be identified from the metabolic networks. METHODS: The main aim of this paper is to review the available techniques in gene knockout strategies for microbial cells. The review is done in terms of their methodology, recent applications in microbial cells. In addition, the advantages and disadvantages of the techniques are compared and discuss and the related patents are also listed as well. RESULTS: Traditionally, gene knockout is done through wet lab (in vivo) techniques, which were conducted through laboratory experiments. However, these techniques are costly and time consuming. Hence, various dry lab (in silico) techniques, where are conducted using computational approaches, have been developed to surmount these problem. CONCLUSION: The development of numerous techniques for gene knockout in microbial cells has brought many advancements in the study of gene functions. Based on the literatures, we found that the gene knockout strategies currently used are sensibly implemented with regard to their benefits. PMID- 27185503 TI - Synergistic strengthening effect of nanocrystalline copper reinforced with carbon nanotubes. AB - In this study, a novel multi-walled carbon nanotubes reinforced nanocrystalline copper matrix composite with super high strength and moderate plasticity was synthesized. We successfully overcome the agglomeration problem of the carbon nanotubes and the grain growth problem of the nanocrystalline copper matrix by combined use of the electroless deposition and spark plasma sintering methods. The yield strength of the composite reach up to 692 MPa, which is increased by 2 and 5 times comparing with those of the nanocrystalline and coarse copper, respectively. Simultaneously, the plasticity of the composite was also significantly increased in contrast with that of the nanocrystalline copper. The increase of the density of the carbon nanotubes after coating, the isolation effect caused by the copper coating, and the improvement of the compatibility between the reinforcements and matrix as well as the effective control of the grain growth of the copper matrix all contribute to improving the mechanical properties of the composite. In addition, a new strengthening mechanism, i.e., the series-connection effect of the nanocrystalline copper grains introduced by carbon nanotubes, is proposed to further explain the mechanical behavior of the nanocomposite. PMID- 27185500 TI - Dynamic structure of plasma fibronectin. AB - Fibronectin is a large vertebrate glycoprotein that is found in soluble and insoluble forms and involved in diverse processes. Protomeric fibronectin is a dimer of subunits, each of which comprises 29-31 modules - 12 type I, two type II and 15-17 type III. Plasma fibronectin is secreted by hepatocytes and circulates in a compact conformation before it binds to cell surfaces, converts to an extended conformation and is assembled into fibronectin fibrils. Here we review biophysical and structural studies that have shed light on how plasma fibronectin transitions from the compact to the extended conformation. The three types of modules each have a well-organized secondary and tertiary structure as defined by NMR and crystallography and have been likened to "beads on a string". There are flexible sequences in the N-terminal tail, between the fifth and sixth type I modules, between the first two and last two of the type III modules, and at the C terminus. Several specific module-module interactions have been identified that likely maintain the compact quaternary structure of circulating fibronectin. The quaternary structure is perturbed in response to binding events, including binding of fibronectin to the surface of vertebrate cells for fibril assembly and to bacterial adhesins. PMID- 27185504 TI - A data-driven concept schema for defining clinical research data needs. AB - OBJECTIVES: The Patient, Intervention, Control/Comparison, and Outcome (PICO) framework is an effective technique for framing a clinical question. We aim to develop the counterpart of PICO to structure clinical research data needs. METHODS: We use a data-driven approach to abstracting key concepts representing clinical research data needs by adapting and extending an expert-derived framework originally developed for defining cancer research data needs. We annotated clinical trial eligibility criteria, EHR data request logs, and data queries to electronic health records (EHR), to extract and harmonize concept classes representing clinical research data needs. We evaluated the class coverage, class preservation from the original framework, schema generalizability, schema understandability, and schema structural correctness through a semi-structured interview with eight multidisciplinary domain experts. We iteratively refined the schema based on the evaluations. RESULTS: Our data driven schema preserved 68% of the 63 classes from the original framework and covered 88% (73/82) of the classes proposed by evaluators. Class coverage for participants of different backgrounds ranged from 60% to 100% with a median value of 95% agreement among the individual evaluators. The schema was found understandable and structurally sound. CONCLUSIONS: Our proposed schema may serve as the counterpart to PICO for improving the research data needs communication between researchers and informaticians. PMID- 27185505 TI - Evaluation of a computer-based bilingual breastfeeding educational program on breastfeeding knowledge, self-efficacy and intent to breastfeed among rural Hispanic women. AB - OBJECTIVE: To evaluate the impact of an interactive, computer based, bi-lingual breastfeeding educational program on breastfeeding knowledge, self-efficacy and intent to breastfeed among rural Hispanic women living in Scottsbluff, Nebraska. METHODS: A two-group, repeated measures quasi-experimental study was conducted to evaluate the impact of a breastfeeding intervention. Forty six rural Hispanic women between ages 18 and 38 years were enrolled at the Regional West Medical Center in Scottsbluff, Nebraska. Study participants were randomized into intervention and control groups, with the intervention group (n=23) receiving bi lingual (English and Spanish) breastfeeding education on a touch screen computer program, while the control group received printed educational material. Study participants were enrolled during their last six weeks of pregnancy, with follow up assessments conducted post-partum at days 3 and 7, weeks 2 and 6, and months 3 and 6. The study protocol was approved by the University of Nebraska Medical Center Institutional Review Board (IRB protocol #430-12-EP) and City University of New York Institutional Review Board (IRB protocol # 642980-1). RESULTS: A significant improvement in the breastfeeding knowledge and intent to breastfeed scores was seen over a 6 month period among all the study participants (p<0.05). There was a gradual increase in the breastfeeding self-efficacy scores till week 6 followed by a decrease in self-efficacy scores at month 3 (p=0.46), and month 6 (P=0.54). Breastfeeding knowledge scores differed significantly between the study participants in the control and intervention groups at week 6 (p=0.03). There were no significant differences in the breastfeeding knowledge between the control and intervention groups at other time points. The control group showed gradual decline in their self-efficacy scores at month 3 and month 6 compared to the intervention group that showed a gradual increase in their self-efficacy scores at different time points during their follow up period. However, there were no significant differences in the self-efficacy scores between the intervention and control groups at different points. The control group showed significantly higher negative breastfeeding sentiment scores compared to the intervention group at days 3 (p=0.02) and 7 (p=0.03) indicating a lower intent to breastfeed. CONCLUSION: Hispanic women living in rural settings showed improvement in breastfeeding knowledge, self-efficacy and intent to breastfeed using the computer based bi-lingual educational program. Results show week 6 and month 3 to be the critical time points of intervention so that women continue to breastfeed. PMID- 27185506 TI - A personalized mobile patient guide system for a patient-centered smart hospital: Lessons learned from a usability test and satisfaction survey in a tertiary university hospital. AB - OBJECTIVE: The present study focused on the design, implementation, and evaluation of a personalized mobile patient guide system that utilizes smart phones, indoor navigation technology and a hospital information system (HIS) to address the difficulties that outpatients face in finding hospital facilities, recognizing their daily treatment schedule, and accessing personalized medical and administrative information. MATERIALS AND METHODS: The present study was conducted in a fully digitized tertiary university hospital in South Korea. We developed a real-time location-based outpatient guide system that consists of Bluetooth access points (APs) for indoor navigation, an Android-based guide application, a guide server, and interfaces with the HIS. A total of 33 subjects and 43 outpatients participated in the usability test (UT) and the satisfaction survey, respectively. RESULTS: We confirmed that the indoor navigation feature can be applied to outpatient departments with precision using a position error test. The participants in the UT completed each scenario with an average success rate of 67.4%. According to the results, we addressed the problems and made improvements to the user interface by providing users with context-based guidance information. The satisfaction rating of the system was high, with an average score of 4.0 out of 5.0, showing its utility as a patient-centered hospital service. CONCLUSION: The innovative mobile patient guide system for outpatients is feasible and can be successfully implemented to provide personalized information with high satisfaction. Additionally, the issues identified and lessons learned from our experiences regarding task scheduling, indoor navigation, and usability should be considered when developing the system. PMID- 27185507 TI - Modular ICT-based patient empowerment framework for self-management of diabetes: Design perspectives and validation results. AB - INTRODUCTION: It is estimated that more than 382 million people suffer from diabetes across the globe, most of which are between the age of 40 and 59 years. ICT can play a key role in better management of diabetes and in patient empowerment. Patient empowerment involves patients to a greater extent in their own healthcare process and disease management becomes an integrated part of their daily life. Self-management opens the possibility for patients to contribute to their own healthcare as well as to be more in control of their disease. OBJECTIVES: The objective of our study was to explore the impact of an ICT-based patient empowerment framework in diabetes self-management. METHODS: A modular patient empowerment framework that fosters diabetes self-management was designed and implemented. The framework incorporates expert knowledge in the form of clinical guidelines, and it supports patients in the specification of personalized activities that are based on medical recommendations and personal goals, and in the collection of observations of daily living. The usability and usefulness of the proposed framework were assessed in a pilot study with the participation of 60 patients and 12 health professionals. RESULTS: The study revealed that a patient empowerment approach based on self-management ICT tools is useful and accepted by both the patients and the physicians. For those patients who were already disciplined in their disease management the piloted solution served as a facilitator for data logging. For the rest, it served as an incentive for better adherence to disease management principles. The ICT tools prompted many patients into becoming more physically active and into making dietary habits' adjustments. However, this impact proved to be tightly correlated with the sociocultural background of the subjects. The study also demonstrated that even in patient-centric self-management interventions the physicians still have a key role to play. However, the acceptance of such interventions by the healthcare professionals depends not only on the level of impact in their patients' disease management but also on the level of impact in their workflow. CONCLUSIONS: It is evident that a patient empowerment approach based on self management ICT tools is useful and accepted by patients and physicians. Further, there are clear indications that ICT frameworks such as the one presented in this paper support patients in behavioral changes and in better disease management. Finally, it was realized that self-management solutions should be built around the objective not only to educate and guide patients in disease self-management, but also to assist them in exploring the decision space and to provide insight and explanations about the impact of their own values on the decision. PMID- 27185508 TI - Smart homes and home health monitoring technologies for older adults: A systematic review. AB - BACKGROUND: Around the world, populations are aging and there is a growing concern about ways that older adults can maintain their health and well-being while living in their homes. OBJECTIVES: The aim of this paper was to conduct a systematic literature review to determine: (1) the levels of technology readiness among older adults and, (2) evidence for smart homes and home-based health monitoring technologies that support aging in place for older adults who have complex needs. RESULTS: We identified and analyzed 48 of 1863 relevant papers. Our analyses found that: (1) technology-readiness level for smart homes and home health monitoring technologies is low; (2) the highest level of evidence is 1b (i.e., one randomized controlled trial with a PEDro score >=6); smart homes and home health monitoring technologies are used to monitor activities of daily living, cognitive decline and mental health, and heart conditions in older adults with complex needs; (3) there is no evidence that smart homes and home health monitoring technologies help address disability prediction and health-related quality of life, or fall prevention; and (4) there is conflicting evidence that smart homes and home health monitoring technologies help address chronic obstructive pulmonary disease. CONCLUSIONS: The level of technology readiness for smart homes and home health monitoring technologies is still low. The highest level of evidence found was in a study that supported home health technologies for use in monitoring activities of daily living, cognitive decline, mental health, and heart conditions in older adults with complex needs. PMID- 27185509 TI - Specific technological communication skills and functional health literacy have no influence on self-reported benefits from enrollment in the TeleCare North trial. AB - PURPOSE: The Danish TeleCare North trial has developed a telehealth system, Telekit, which is used for self-management by patients diagnosed with chronic obstructive pulmonary disease (COPD). Self-management is the engagement in one's own illness and health by monitoring and managing one's symptoms and signs of illness. The study examines the association between COPD patients' use of Telekit and their functional health literacy and the association between their use of Telekit and their specific technological communication skills. METHODS: A consecutive sample of participants (n=60) from the TeleCare North trial were recruited. Face-to-face interviews were conducted with each participant to collect demographic data. Functional health literacy was measured with the Danish TOFHLA test. Participants completed a non-standardised questionnaire about their health status, their use of the Telekit system, and their specific technological communication skills. Binary logistic regressions were performed to examine how functional health literacy and specific technological communication skills influenced the use of Telekit by giving users an enhanced sense of freedom, security, control, and a greater awareness of COPD symptoms. RESULTS: Participants (27 women, 33 men) had a mean age of 70 (SD: 8.37) years. Functional health literacy levels were classified as inadequate in 14 (23%) participants, as marginal in 12 (20%), and as adequate in 34 (57%). Participants self-reported a feeling of increased security (72%), greater freedom (27%), more control (62%), and greater awareness of symptoms (50%) when using Telekit. The use of Telekit was not significantly associated with levels of functional health literacy or with the number of specific technological communication skills (p>0.05) based on the binary logistic regressions. CONCLUSION: The enhanced sense of security, freedom, control, and the greater awareness of COPD symptoms achieved by using Telekit were unassociated both with the patients' score of functional health literacy and with their specific technological communication skills. On the basis of our results it seems that the specific technological communication skills and functional health literacy are not a prerequisite for the use of the Telekit system. PMID- 27185510 TI - Social media and flu: Media Twitter accounts as agenda setters. AB - OBJECTIVES: This paper has two objectives. First, it categorizes the Twitter handles tweeted flu related information based on the amount of replies and mentions within the Twitter network. The collected Twitter accounts are categorized as media, health related individuals, organizations, government, individuals with no background with media or medical field, in order to test the relationship between centrality measures of the accounts and their categories. The second objective is to examine the relationship between the importance of the Twitter accounts in the network, centrality measures, and specific characteristics of each account, including the number of tweets and followers as well as the number of accounts followed and liked. METHODS: Using Twitter search network API, tweets with "flu" keyword were collected and tabulated. Network centralities were calculated with network analysis tool, NodeXL. The collected Twitters accounts were content analyzed and categorized by multiple coders. RESULTS: When the media or organizational Twitter accounts were present in the list of important Twitter accounts, they were highly effective disseminating flu related information. Also, they were more likely to stay active one year after the data collection period compared to other influential individual accounts. CONCLUSIONS: Health campaigns are recommended to focus on recruiting influential Twitter accounts and encouraging them to retweet or mention in order to produce better results in disseminating information. Although some individual social media users were valuable assets in terms of spreading information about flu, media and organization handles were more reliable information distributors. Thus, health information practitioners are advised to design health campaigns better utilizing media and organizations rather than individuals to achieve consistent and efficient campaign outcomes. PMID- 27185511 TI - Eosinophilic pleural effusion as a manifestation of idiopathic hypereosinophilic syndrome. PMID- 27185512 TI - Incidental pulmonary lymphangioleiomyomatosis in a patient with breast cancer. PMID- 27185513 TI - Landing strategies focusing on the control of tibial rotation in the initial contact period of one-leg forward hops. AB - Anterior cruciate ligament (ACL) reconstruction (ACLR) surgeries successfully restore anterior tibial translation but not tibial rotation. This study aimed to explore landing strategies focusing on the control of tibial rotation at landing when the ACL is most vulnerable. Three groups of male subjects (50 ACLRs, 26 basketball players, and 31 controls) participated in one-leg forward hop tests for determining the tibial rotatory landing strategies adopted during the initial landing phase. The differences in knee kinematics and muscle activities between internal and external tibial rotatory (ITR, ETR) landing strategies were examined. A higher proportion of basketball players (34.6%) were found to adopt ITR strategies (controls: 6.5%), exhibiting significantly greater hopping distance and knee strength. After adjusting for hopping distance, subjects adopting ITR strategies were found to hop faster with straighter knees at foot contact and with greater ITR and less knee adduction angular displacement during the initial landing phase. However, significantly greater angular displacement in knee flexion, greater medial hamstring activities, and greater co-contraction index of hamstrings and medial knee muscles were also found during initial landing. Our results support the importance of the recruitments of medial hamstrings or the local co-contraction in assisting the rotatory control of the knee during initial landing for avoiding ACL injuries. PMID- 27185514 TI - Transperineal ultrasonography: First level exam in IBD patients with perianal disease. AB - BACKGROUND: A pelvic magnetic resonance imaging (MRI) represents the front-line method for evaluating perianal disease in patients with inflammatory bowel disease (IBD). Recently, transperineal ultrasonography (TPUS) has been proposed as a simple, safe, time-sparing and useful diagnostic technique to assess different pathological conditions of the pelvic floor. AIM: The aim of this prospective single centre study was to evaluate the accuracy of TPUS versus MRI for the detection and classification of perineal disease in IBD patients. METHODS: From November 2013 to November 2014, 28 IBD patients underwent either TPUS or MRI. Fistulae and abscesses were classified according to Parks' and AGA's classification methods. A concordance was assessed by k statistics. RESULTS: Overall, 33 fistulae and 8 abscesses were recognized by TPUS (30 and 7 by MRI, respectively). The agreement between TPUS and MRI was 75% according to Parks' classification (k=0.67) and 86% according to AGA classification (k=0.83), while it was 36% (k=0.34) for classifying abscesses. CONCLUSIONS: TPUS proved to be as accurate as MRI for detecting superficial and small abscesses and for classifying perianal disease. Both examinations may be performed at the initial presentation of the patient, but TPUS is a cheaper, time-sparing procedure. The optimal use of TPUS might be in follow-up patients. PMID- 27185515 TI - High-Throughput Quantitative Lipidomics Analysis of Nonesterified Fatty Acids in Human Plasma. AB - We present a high-throughput, nontargeted lipidomics approach using liquid chromatography coupled to high-resolution mass spectrometry for quantitative analysis of nonesterified fatty acids. We applied this method to screen a wide range of fatty acids from medium-chain to very long-chain (8 to 24 carbon atoms) in human plasma samples. The method enables us to chromatographically separate branched-chain species from their straight-chain isomers as well as separate biologically important omega-3 and omega-6 polyunsaturated fatty acids. We used 51 fatty acid species to demonstrate the quantitative capability of this method with quantification limits in the nanomolar range; however, this method is not limited only to these fatty acid species. High-throughput sample preparation was developed and carried out on a robotic platform that allows extraction of 96 samples simultaneously within 3 h. This high-throughput platform was used to assess the influence of different types of human plasma collection and preparation on the nonesterified fatty acid profile of healthy donors. Use of the anticoagulants EDTA and heparin has been compared with simple clotting, and only limited changes have been detected in most nonesterified fatty acid concentrations. PMID- 27185518 TI - MeiLan Han: putting COPD care on the map. PMID- 27185516 TI - Intra-left ventricular flow dynamics in patients with preserved and impaired left ventricular function: Analysis with 3D cine phase contrast MRI (4D-Flow). AB - PURPOSE: To examine how left ventricular (LV) volume and function affect flow dynamics by analyzing 3D intra-LV vortex features using 4D-Flow. MATERIALS AND METHODS: Twenty-one patients with preserved (LVEF > 60%) and 14 with impaired LV function (LVEF < 40%) underwent 4D-Flow (at 3T). RESULTS: In patients with preserved LV function, the intra-LV vortices developed in both the early and late diastolic phases. The shift of inflow vectors at the basal LV toward the posterior-lateral side of the LV and the mid-ventricular turn of inflow vectors toward the LV outflow could explain clearer vortex formation in the late diastolic phase. In patients with impaired LV function, the intra-LV vortices during the diastolic phase located at the more apical LV were larger and more spherically shaped. Both the distance to the vortex core and the vortex area correlated significantly with LV end-diastolic volume (r = 0.66 and 0.73), LVEF (r = -0.74 and -0.68), LV sphericity index (r = -0.60 and -0.65), and peak filling rate (r = -0.61 and -0.64), respectively (P < 0.01). The intra-LV vortices developed during the systolic phase in 10 cases. In those, some of the particles at the apical LV rotated within the LV, whereas in patients with preserved LV function, all of the particles were directed straight to the ascending aorta with accelerated flow velocity (256.8 +/- 120.2 cm/s vs. 414.3 +/ 88.2 cm/s, P < 0.01). CONCLUSION: Vortex formation during the diastolic phase may be critical for both LV filling and ejection. 4D-Flow showed the 3D alterations of intra-LV flow dynamics by LV dilatation and dysfunction in a noninvasive and comprehensive manner. J. Magn. Reson. Imaging 2016;44:1493-1503. PMID- 27185517 TI - Generation of a MLL-AF9-specific stem cell model of acute monocytic leukemia. AB - Acute monocytic leukemia (AML-M5), a subtype of acute myeloid leukemia (AML), affects mostly young children and has poor prognosis. The mechanisms of treatment failure of AML-M5 are still unclear. In this study, we generated iPSC from THP-1 cells from a patient with AML-M5, using retroviruses encoding the pluripotency associated genes (OCT3/4, SOX2, KLF4 and c-MYC). These AML-M5-derived iPSC showed features similar with those of human embryonic stem cells in terms of the morphology, gene expression, protein/antigen expression and differentiation capability. Parental-specific markers were down-regulated in these AML-M5-derived iPSCs. Expression of MLL-AF9 fusion gene (previously identified to be associated with pathogenesis of AML-M5) was observed in all iPSC clones as well as parental cells. We conclude that AML-M5-specific iPSC clones have been successfully developed. This disease model may provide a novel approach for future study of pathogenesis and therapeutic intervention of AML-M5. PMID- 27185519 TI - Successes and challenges of COPD management in Australia: reflections on the past and future. PMID- 27185521 TI - COPD service delivery in the UK. PMID- 27185520 TI - Meeting the challenge of COPD care delivery in the USA: a multiprovider perspective. AB - The burden of chronic obstructive pulmonary disease (COPD) in the USA continues to grow. Although progress has been made in the the development of diagnostics, therapeutics, and care guidelines, whether patients' quality of life is improved will ultimately depend on the actual implementation of care and an individual patient's access to that care. In this Commission, we summarise expert opinion from key stakeholders-patients, caregivers, and medical professionals, as well as representatives from health systems, insurance companies, and industry-to understand barriers to care delivery and propose potential solutions. Health care in the USA is delivered through a patchwork of provider networks, with a wide variation in access to care depending on a patient's insurance, geographical location, and socioeconomic status. Furthermore, Medicare's complicated coverage and reimbursement structure pose unique challenges for patients with chronic respiratory disease who might need access to several types of services. Throughout this Commission, recurring themes include poor guideline implementation among health-care providers and poor patient access to key treatments such as affordable maintenance drugs and pulmonary rehabilitation. Although much attention has recently been focused on the reduction of hospital readmissions for COPD exacerbations, health systems in the USA struggle to meet these goals, and methods to reduce readmissions have not been proven. There are no easy solutions, but engaging patients and innovative thinkers in the development of solutions is crucial. Financial incentives might be important in raising engagement of providers and health systems. Lowering co-pays for maintenance drugs could result in improved adherence and, ultimately, decreased overall health-care spending. Given the substantial geographical diversity, health systems will need to find their own solutions to improve care coordination and integration, until better data for interventions that are universally effective become available. PMID- 27185522 TI - Prevention and management of COPD in China: successes and major challenges. PMID- 27185523 TI - Chemistry Testing on Plasma Versus Serum Samples in Dialysis Patients: Clinical and Quality Improvement Implications. AB - Plasma samples collected in tubes containing separator gels have replaced serum samples for most chemistry tests in many hospital and commercial laboratories. Use of plasma samples for blood tests in the dialysis population eliminates delays in sample processing while waiting for clotting to complete, laboratory technical issues associated with fibrin formation, repeat sample collection, and patient care issues caused by delay of results because of incompletely clotted specimens. Additionally, a larger volume of plasma is produced than serum for the same amount of blood collected. Plasma samples are also acceptable for most chemical tests involved in the care of patients with ESRD. This information becomes very important when United States regulatory requirements for ESRD inadvertently limit the type of sample that can be used for government reporting, quality assessment, and value-based payment initiatives. In this narrative, we summarize the renal community experience and how the subsequent resolution of the acceptability of phosphorus levels measured from serum and plasma samples may have significant implications in the country's continued development of a value based Medicare ESRD Quality Incentive Program. PMID- 27185525 TI - Hepatocytes as in vitro test system to investigate metabolite patterns of pesticides in farmed rainbow trout and common carp: Comparison between in vivo and in vitro and across species. AB - In vitro tools using isolated primary fish hepatocytes have been proposed as a useful model to study the hepatic metabolism of xenobiotics in fish. In order to evaluate the potential of in vitro fish hepatocyte assays to provide information on in vivo metabolite patterns of pesticides in farmed fish, the present study addressed the following questions: Are in vitro and in vivo metabolite patterns comparable? Are species specific differences of metabolite patterns in vivo reflected in vitro? Are metabolite patterns obtained from cryopreserved hepatocytes comparable to those from freshly isolated cells? Rainbow trout and common carp were dosed orally with feed containing the pesticide methoxychlor (MXC) for 14days. In parallel, in vitro incubations using suspensions of freshly isolated or cryopreserved primary hepatocytes obtained from both species were performed. In vivo and in vitro samples were analyzed by thin-layer chromatography with authentic standards supported by HPLC-MS. Comparable metabolite patterns from a qualitative perspective were observed in liver in vivo and in hepatocyte suspensions in vitro. Species specific differences of MXC metabolite patterns observed between rainbow trout and common carp in vivo were well reflected by experiments with hepatocytes in vitro. Finally, cryopreserved hepatocytes produced comparable metabolite patterns to freshly isolated cells. The results of this study indicate that the in vitro hepatocyte assay could be used to identify metabolite patterns of pesticides in farmed fish and could thus serve as a valuable tool to support in vivo studies as required for pesticides approval according to the EU regulation 1107. PMID- 27185524 TI - Iron Therapy Challenges for the Treatment of Nondialysis CKD Patients. AB - The clinical consequences of untreated, severe anemia in patients with nondialysis CKD can be significant, but disparities exist in the anemia treatment guidelines and position papers issued from working groups and associations across the world. These differ in hemoglobin target and iron levels and their emphasis on various iron markers and other clinical outcomes. Not surprisingly, disparities are observed in anemia treatment strategies among patients with nondialysis CKD across different areas of the world. Over the past decade, the prescription and dosage of both iron therapies and erythropoiesis-stimulating agents have shifted, with notable regional differences observed. Moreover, there is ongoing debate regarding oral versus intravenous administration of iron. Compared with oral iron therapy, which often leads to gastrointestinal adverse events, low patient adherence, and low efficacy, intravenous iron administration has been associated with potential serious adverse events, such as anaphylaxis. New iron-based compounds and drugs currently under development are reviewed to describe their potential benefits in the treatment of anemia in patients with CKD. New oral compounds, including iron-based phosphate binders, heme iron polypeptide, and liposomal iron, show different rates of absorption with possibly different efficacy and improved tolerability. These new potential therapies offer health care providers additional anemia treatment options for their patients with CKD; however, the management of anemia in the CKD population continues to present challenges that require prospective studies to identify the optimal iron therapy for patients. PMID- 27185528 TI - Barriers and facilitators to health information exchange in low- and middle income country settings: a systematic review. AB - The exchange and use of health information can help healthcare professionals and policymakers make informed decisions on ways of improving patient and population health. Many low- and middle-income countries (LMICs) have however failed to embrace the approaches and technologies to facilitate health information exchange (HIE). We sought to understand the barriers and facilitators to the implementation and adoption of HIE in LMICs. Two reviewers independently searched 11 academic databases for published and on-going qualitative, quantitative and mixed-method studies and searched for unpublished work through the Google search engine. The searches covered the period from January 1990 to July 2014 and were not restricted by language. Eligible studies were independently, critically appraised and then thematically analysed. The searches yielded 5461 citations after de-duplication of results. Of these, 56 articles, three conference abstracts and four technical reports met the inclusion criteria. The lack of importance given to data in decision making, corruption and insecurity, lack of training and poor infrastructure were considered to be major challenges to implementing HIE, but strong leadership and clear policy direction coupled with the financial support to acquire essential technology, improve the communication network, and provide training for staff all helped to promote implementation. The body of work also highlighted how implementers of HIE needed to take into account local needs to ensure that stakeholders saw HIE as relevant and advantageous. HIE interventions implemented through leapfrog technologies such as telehealth/telemedicine and mHealth in Brazil, Kenya, and South Africa, provided successful examples of exchanging health information in LMICs despite limited resources and capability. It is important that implementation of HIE is aligned with national priorities and local needs. PMID- 27185529 TI - Presence of Distractor Improves Time Estimation Performance in an Adult ADHD Sample. AB - OBJECTIVE: It is widely accepted that patients with ADHD exhibit greater susceptibility to distractors, especially during tasks with higher working memory load demands. However, no study to date has specifically measured the impact of distractors on timing functions, although these have consistently shown alterations in ADHD. In this investigation, we aimed to elucidate the neural mechanisms mediating distractor effects on timing functions. METHOD: We employed a time estimation functional magnetic resonance imaging (fMRI) paradigm I: ncluding a distracting element in half of the trials in a sample of 21 patients with ADHD and 24 healthy controls. RESULTS: As expected, the effect of the distractor was greater in ADHD patients, where it was associated with increased orbitofrontal activity compared with controls. Behaviorally, time estimation performance benefited from the presence of distractors in both groups. In turn, such improvement correlated with medial frontal and insular activity in the brain. CONCLUSION: These results suggest that distractors could be stimulating recruitment of frontal resources in ADHD, thus contributing to increase focus on the task. PMID- 27185530 TI - Harvard relaxes COI rules for clinical researchers. PMID- 27185527 TI - Dynamic NF-kappaB and E2F interactions control the priority and timing of inflammatory signalling and cell proliferation. AB - Dynamic cellular systems reprogram gene expression to ensure appropriate cellular fate responses to specific extracellular cues. Here we demonstrate that the dynamics of Nuclear Factor kappa B (NF-kappaB) signalling and the cell cycle are prioritised differently depending on the timing of an inflammatory signal. Using iterative experimental and computational analyses, we show physical and functional interactions between NF-kappaB and the E2 Factor 1 (E2F-1) and E2 Factor 4 (E2F-4) cell cycle regulators. These interactions modulate the NF-kappaB response. In S-phase, the NF-kappaB response was delayed or repressed, while cell cycle progression was unimpeded. By contrast, activation of NF-kappaB at the G1/S boundary resulted in a longer cell cycle and more synchronous initial NF-kappaB responses between cells. These data identify new mechanisms by which the cellular response to stress is differentially controlled at different stages of the cell cycle. PMID- 27185526 TI - Hedgehog signaling is a potent regulator of liver lipid metabolism and reveals a GLI-code associated with steatosis. AB - Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in industrialized countries and is increasing in prevalence. The pathomechanisms, however, are poorly understood. This study assessed the unexpected role of the Hedgehog pathway in adult liver lipid metabolism. Using transgenic mice with conditional hepatocyte-specific deletion of Smoothened in adult mice, we showed that hepatocellular inhibition of Hedgehog signaling leads to steatosis by altering the abundance of the transcription factors GLI1 and GLI3. This steatotic 'Gli-code' caused the modulation of a complex network of lipogenic transcription factors and enzymes, including SREBP1 and PNPLA3, as demonstrated by microarray analysis and siRNA experiments and could be confirmed in other steatotic mouse models as well as in steatotic human livers. Conversely, activation of the Hedgehog pathway reversed the "Gli-code" and mitigated hepatic steatosis. Collectively, our results reveal that dysfunctions in the Hedgehog pathway play an important role in hepatic steatosis and beyond. PMID- 27185531 TI - Effects of cue focality on the neural mechanisms of prospective memory: A meta analysis of neuroimaging studies. AB - Remembering to execute pre-defined intentions at the appropriate time in the future is typically referred to as Prospective Memory (PM). Studies of PM showed that distinct cognitive processes underlie the execution of delayed intentions depending on whether the cue associated with such intentions is focal to ongoing activity processing or not (i.e., cue focality). The present activation likelihood estimation (ALE) meta-analysis revealed several differences in brain activity as a function of focality of the PM cue. The retrieval of intention is supported mainly by left anterior prefrontal cortex (Brodmann Area, BA 10) in nonfocal tasks, and by cerebellum and ventral parietal regions in focal tasks. Furthermore, the precuneus showed increased activation during the maintenance phase of intentions compared to the retrieval phase in nonfocal tasks, whereas the inferior parietal lobule showed increased activation during the retrieval of intention compared to maintenance phase in the focal tasks. Finally, the retrieval of intention relies more on the activity in anterior cingulate cortex for nonfocal tasks, and on posterior cingulate cortex for focal tasks. Such focality-related pattern of activations suggests that prospective remembering is mediated mainly by top-down and stimulus-independent processes in nonfocal tasks, whereas by more automatic, bottom-up, processes in focal tasks. PMID- 27185532 TI - Spatially explicit estimates of N2 O emissions from croplands suggest climate mitigation opportunities from improved fertilizer management. AB - With increasing nitrogen (N) application to croplands required to support growing food demand, mitigating N2 O emissions from agricultural soils is a global challenge. National greenhouse gas emissions accounting typically estimates N2 O emissions at the country scale by aggregating all crops, under the assumption that N2 O emissions are linearly related to N application. However, field studies and meta-analyses indicate a nonlinear relationship, in which N2 O emissions are relatively greater at higher N application rates. Here, we apply a super-linear emissions response model to crop-specific, spatially explicit synthetic N fertilizer and manure N inputs to provide subnational accounting of global N2 O emissions from croplands. We estimate 0.66 Tg of N2 O-N direct global emissions circa 2000, with 50% of emissions concentrated in 13% of harvested area. Compared to estimates from the IPCC Tier 1 linear model, our updated N2 O emissions range from 20% to 40% lower throughout sub-Saharan Africa and Eastern Europe, to >120% greater in some Western European countries. At low N application rates, the weak nonlinear response of N2 O emissions suggests that relatively large increases in N fertilizer application would generate relatively small increases in N2 O emissions. As aggregated fertilizer data generate underestimation bias in nonlinear models, high-resolution N application data are critical to support accurate N2 O emissions estimates. PMID- 27185533 TI - Structure of the Membrane-intrinsic Nitric Oxide Reductase from Roseobacter denitrificans. AB - Membrane-intrinsic nitric oxide reductases (NORs) are key components of bacterial denitrification pathways with a close evolutionary relationship to the cytochrome oxidase (COX) complex found in aerobic respiratory chains. A key distinction between COX and NOR is the identity of the metal directly opposite heme b3 within the active site. In NOR, this metal is iron (FeB), whereas in COX, it is copper (CuB). The purified NOR of Roseobacter denitrificans contains copper and has modest oxidase activity, raising the possibility that a COX-like active site might have independently arisen within the context of a NOR-like protein scaffold. Here we present the crystal structure of the Roseobacter denitrificans NorBC complex and anomalous scattering experiments probing the identity of each metal center. Our results refute the hypothesis that copper occupies the active site and instead reveal a new metal center in the small subunit not seen in any other NOR or COX. PMID- 27185534 TI - Demystifying the Courtroom: Everything the Veterinary Pathologist Needs to Know About Testifying in an Animal Cruelty Case. AB - When veterinary pathologists testify as expert witnesses in animal cruelty trials, they may find themselves in an intimidating and unfamiliar environment. The legal rules are clouded in mystery, the lawyers dwell on mundane details, and the witness's words are extracted with precision by a verbal scalpel. An unprepared expert witness can feel ungrounded and stripped of confidence. The goal of this article is to lift the veil of mystery and give the veterinary pathologist the tools to be a knowledgeable and confident expert witness before and during testimony. This article discusses the types of expert witnesses, disclosure requirements and the importance of a good report, the legal basics of expert testimony, and how to be an effective expert witness. The article references Minnesota law; however, the laws are similar in most jurisdictions and based on the same constitutional requirements, and the concepts presented are applicable in nearly every courtroom.(1). PMID- 27185535 TI - Modelling bidirectional modulations in synaptic plasticity: A biochemical pathway model to understand the emergence of long term potentiation (LTP) and long term depression (LTD). AB - Synaptic plasticity induces bidirectional modulations of the postsynaptic response following a synaptic transmission. The long term forms of synaptic plasticity, named long term potentiation (LTP) and long term depression (LTD), are critical for the antithetic functions of the memory system, memory formation and removal, respectively. A common Ca(2+) signalling upstream triggers both LTP and LTD, and the critical proteins and factors coordinating the LTP/LTD inductions are not well understood. We develop an integrated model based on the sub-models of the indispensable synaptic proteins in the emergence of synaptic plasticity to validate and understand their potential roles in the expression of synaptic plasticity. The model explains Ca(2+)/calmodulin (CaM) complex dependent coordination of LTP/LTD expressions by the interactions among the indispensable proteins using the experimentally estimated kinetic parameters. Analysis of the integrated model provides us with insights into the effective timescales of the key proteins and we conclude that the CaM pool size is critical for the coordination between LTP/LTD expressions. PMID- 27185536 TI - Comparative molecular field analysis and molecular docking studies on novel aryl chalcone derivatives against an important drug target cysteine protease in Plasmodium falciparum. AB - The computational studies namely molecular docking simulations and Comparative Molecular Field Analysis (CoMFA) are executed on series of 52 novel aryl chalcones derivatives using Plasmodium falciparum cysteine proteases (falcipain - 2) as vital target. In the present study, the correlation between different molecular field effects namely steric and electrostatic interactions and chemical structures to the inhibitory activities of novel aryl chalcone derivatives is inferred to perceive the major structural prerequisites for the rational design and development of potent and novel lead anti-malarial compound. The apparent binding conformations of all the compounds at the active site of falcipain - 2 and the hydrogen-bond interactions which could be used to modify the inhibitory activities are identified by using Surflex-dock study. Statistically significant CoMFA model has been developed with the cross-validated correlation coefficient (q(2)) of 0.912 and the non-cross-validated correlation coefficient (r(2)) of 0.901. Standard error of estimation (SEE) of 0.210, with the optimum number of components is ten. The predictability of the derived model is examined with a test set consists of sixteen compounds and the predicted r(2) value is found to be 0.924. The docking and QSAR study results confer crucial suggestions for the optimization of novel 1,3-diphenyl-2-propen-1-one derivatives and synthesis of effective anti- malarial compounds. PMID- 27185537 TI - Endovascular Treatment of 147 Cases of Cavernous Carotid Aneurysms: A Single Center Experience. AB - BACKGROUND: Cavernous carotid aneurysms (CCAs) are characterized by pain and neuro-ophthalmologic deficits. The optimal treatment remains unclear, especially for asymptomatic CCAs. This study investigated the efficacy of endovascular treatment for CCAs in our center. METHODS: Data obtained from patients who underwent endovascular treatment for CCAs from July 2011 to July 2014 were reviewed. A retrospective analysis was conducted regarding the general condition, clinical presentation, aneurysm characteristics, therapeutic strategy, and prognosis of CCA patients. RESULTS: One hundred forty-seven patients who exhibited 155 CCAs were included, which comprised 46 asymptomatic and 101 symptomatic CCA cases. Forty-eight cases presented with headache, 5 cases presented with subarachnoid hemorrhage, 20 cases presented with diplopia, 38 cases presented with cranial nerve palsy, and 27 cases presented with ischemic stroke. The mean aneurysm sizes were 15.3 +/- 12.2 and 8.1 +/- 7.1 mm in the symptomatic and asymptomatic groups, respectively. Different treatments were administered: coil occlusion (n = 15), stent/balloon-assisted coil occlusion (n = 123), and parent artery occlusion (PAO) (n = 17). The PAO-treated group exhibited the highest aneurysm occlusion rate. Follow-up data were available for 131 cases, which included 86 symptomatic and 45 asymptomatic cases. There were no deaths. Among the symptomatic patients, 40.7% improved, 58.1% remained stable, and 1.2% worsened; 12 patients exhibited regrowth and 6 patients had repeated endovascular treatment. The asymptomatic patients remained stable, including 5 patients who exhibited regrowth and 2 patients who had repeated endovascular treatment. CONCLUSION: Endovascular treatment is safe and effective for CCAs and should be considered in patients with minimal complications, as well as in asymptomatic patients with stable symptoms. PMID- 27185538 TI - Food safety in Thailand. 3: Pesticide residues detected in mangosteen (Garcinia mangostana L.), queen of fruits. AB - BACKGROUND: For developing countries like Thailand, regulation of pesticide usage exists, but it is not fully enforced. Therefore, pesticide residues in vegetables and fruits have not been well monitored. This study aimed to determine the pesticide residues in mangosteen fruits sold in Thailand. The mangosteen samples (n = 111) were purchased and the contents of 28 pesticides were analysed by GC MS/MS method. RESULTS: Of the pesticides tested, eight were found in 100% of the mangosteen samples. However, in 97% of these samples, either chlorothalonil, chlorpyrifos, diazinon, dimethoate, metalaxyl or profenofos was detected exceeding their maximum residue limits (MRLs), representing a 97% rate of pesticide detection above the MRL. This rate is much higher than those found in other fruits sold in developed countries. However, this conclusion excludes the fresh Thai mangosteens grown for export, as these are generally cultivated and harvested to GAP standards. Since the edible part of the mangosteen is the pulp, washing the fruits with running water can reduce the risk of pesticide residues contaminating the pulp which would be eaten by the consumer. CONCLUSION: The findings strongly suggest that routine monitoring of pesticide residues in fruits and vegetables is required to reduce the health risks associated with consuming contaminated food. (c) 2016 Society of Chemical Industry. PMID- 27185540 TI - First metabolic profile of PV8, a novel synthetic cathinone, in human hepatocytes and urine by high-resolution mass spectrometry. AB - Novel psychoactive substances (NPS) are ever changing on the drug market, making it difficult for toxicology laboratory methods to stay current with so many new drugs. Recently, PV8, a synthetic pyrrolidinophenone, was detected in seized products in Japan (2013), The Netherlands (2014), and Germany (2014). There are no controlled PV8 administration studies, and no pharmacodynamic and pharmacokinetic data. The objective was to determine PV8's metabolic stability in human liver microsome (HLM) incubation and its metabolism following human hepatocyte incubation and high-resolution mass spectrometry (HRMS) with a Thermo Scientific Q-Exactive. Data were acquired with a full-scan data-dependent mass spectrometry method. Scans were thoroughly data mined with different data processing algorithms and analyzed in WebMetaBase. PV8 exhibited a relatively short 28.8 min half-life, with an intrinsic 24.2 MUL/min/mg microsomal clearance. This compound is predicted to be an intermediate clearance drug with an estimated human 22.7 mL/min/kg hepatic clearance. Metabolic pathways identified in vitro included: hydroxylation, ketone reduction, carboxylation, N-dealkylation, iminium formation, dehydrogenation, N-oxidation, and carbonylation. The top three in vitro metabolic pathways were di-hydroxylation > ketone reduction > gamma-lactam formation. Authentic urine specimen analyses revealed the top three metabolic pathways were aliphatic hydroxylation > ketone reduction + aliphatic hydroxylation > aliphatic carboxylation, although the most prominent peak was parent PV8. These data provide useful urinary metabolite targets (aliphatic hydroxylation, aliphatic hydroxylation + ketone reduction, aliphatic carboxylation, and di-hydroxylation) for forensic and clinical testing, and focus reference standard companies' synthetic efforts to provide commercially available standards needed for PV8 biological specimen testing. Graphical Abstract Top four PV8 metabolites identified in vitro. Biotransformations highlighted in blue. Markush structures presented when exact location of biotransformation is unknown. PMID- 27185539 TI - Modeling Physical Stability of Amorphous Solids Based on Temperature and Moisture Stresses. AB - Isothermal microcalorimetry was utilized to monitor the crystallization process of amorphous ritonavir (RTV) and its hydroxypropylmethylcellulose acetate succinate-based amorphous solid dispersion under various stressed conditions. An empirical model was developed: ln(tau)=ln(A)+EaRT-b?wc, where tau is the crystallization induction period, A is a pre-exponential factor, Ea is the apparent activation energy, b is the moisture sensitivity parameter, and wc is water content. To minimize the propagation of errors associated with the estimates, a nonlinear approach was used to calculate mean estimates and confidence intervals. The physical stability of neat amorphous RTV and RTV in hydroxypropylmethylcellulose acetate succinate solid dispersions was found to be mainly governed by the nucleation kinetic process. The impact of polymers and moisture on the crystallization process can be quantitatively described by Ea and b in this Arrhenius-type model. The good agreement between the measured values under some less stressful test conditions and those predicted, reflected by the slope and R(2) of the correlation plot of these 2 sets of data on a natural logarithm scale, indicates its predictability of long-term physical stability of amorphous RTV in solid dispersions. To further improve the model, more understanding of the impact of temperature and moisture on the amorphous physical stability and fundamentals regarding nucleation and crystallization is needed. PMID- 27185541 TI - Identification of in vitro and in vivo human metabolites of the new psychoactive substance nitracaine by liquid chromatography coupled to quadrupole time-of flight mass spectrometry. AB - The purpose of this work was to investigate the in vitro metabolism of nitracaine, a new psychoactive substance, using human liver microsome incubations, to evaluate the cytochrome P450 (CYP) enzyme isoforms responsible for the phase-I metabolism and to compare the information from the in vitro experiments with data resulting from an authentic user's urine sample. Accurate mass spectra of metabolites were obtained using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) and were used in the structural identification of metabolites. Two major and three minor phase-I metabolites were identified from the in vitro experiments. The observed phase-I metabolites were formed through N-deethylation, N,N-deethylation, N-hydroxylation, and de esterification, with CYP2B6 and CYP2C19 being the main enzymes catalyzing their formation. One glucuronidated product was identified in the phase-II metabolism experiments. All of these metabolites are reported for the first time in this study except the N-deethylation product. All the in vitro metabolites except the minor N,N-deethylation product were also present in the human urine sample, thus demonstrating the reliability of the in vitro experiments in the prediction of the in vivo metabolism of nitracaine. In addition to the metabolites, three transformation products (p-nitrobenzoic acid, p-aminobenzoic acid, and 3 (diethylamino)-2,2-dimethylpropan-1-ol) were identified, as well as several glucuronides and glutamine derived of them. PMID- 27185543 TI - Paper-based assay for red blood cell antigen typing by the indirect antiglobulin test. AB - A rapid and simple paper-based elution assay for red blood cell antigen typing by the indirect antiglobulin test (IAT) was established. This allows to type blood using IgG antibodies for the important blood groups in which IgM antibodies do not exist. Red blood cells incubated with IgG anti-D were washed with saline and spotted onto the paper assay pre-treated with anti-IgG. The blood spot was eluted with an elution buffer solution in a chromatography tank. Positive samples were identified by the agglutinated and fixed red blood cells on the original spotting area, while red blood cells from negative samples completely eluted away from the spot of origin. Optimum concentrations for both anti-IgG and anti-D were identified to eliminate the washing step after the incubation phase. Based on the no-washing procedure, the critical variables were investigated to establish the optimal conditions for the paper-based assay. Two hundred ten donor blood samples were tested in optimal conditions for the paper test with anti-D and anti-Kell. Positive and negative samples were clearly distinguished. This assay opens up new applications of the IAT on paper including antibody detection and blood donor recipient crossmatching and extends its uses into non-blood typing applications with IgG antibody-based diagnostics. Graphical abstract A rapid and simple paper based assay for red blood cell antigen typing by the indirect antiglobulin test. PMID- 27185544 TI - Gene therapies: the challenge of super-high-cost treatments and how to pay for them. AB - Gene therapies have the potential to cure rare conditions that often have no current efficacious treatments with a one-time treatment episode, relieving substantial unmet need and having profound positive impact on patients' lives. However, with the first gene therapy now licensed and priced at around US$1 million per patient, cost and uncertain funding mechanisms present a potential barrier to patient access. In this article, we discuss the unique challenges presented by gene therapies, particularly concerning the uncertainty inherent in their clinical evidence package at launch and their affordability within strained healthcare budgets. We present several payment models that would allow for sustainable reimbursement of these innovative technologies and make recommendations pertinent both to those developing gene therapies and to those paying for them. PMID- 27185542 TI - Generation of electrochemiluminescence at bipolar electrodes: concepts and applications. AB - Bipolar electrochemistry (BPE) is an unconventional technique where a conducting object is addressed electrochemically in an electrolyte without any wire connection with an external power supply. BPE has been known for decades but remained limited to only a couple of niche applications. However, it is now undergoing a true renewal of interest especially in the context of analytical chemistry. The bipolar electrode exhibits two distinct poles of opposite polarization with respect to the solution. This allows one to separate the localization of sensing elements versus reporting ones. Also, arrays of bipolar microelectrodes can be addressed simultaneously to perform parallel analyses. Among several reporting strategies, the combination of BPE with electro chemiluminescence (ECL) is the most frequent choice owing to the very simple visual readout provided by ECL. This article reviews the field from the initial reports to the most recent ones, revealing numerous opportunities including novel analytical strategies for the detection of small molecular analytes and biorelevant molecules such as DNA, RNA, peptides, or other biomarkers. Graphical Abstract Principle of electrochemiluminescence generation at one extremity of a bipolar electrode. PMID- 27185547 TI - The Genomic Landscape of Position Effects on Protein Expression Level and Noise in Yeast. AB - Position effect, the influence of the chromosomal location of a gene on its activity, is a fundamental property of the genome. By placing a GFP gene cassette at 482 different locations across all chromosomes in budding yeast, we quantified the position effects on protein expression level and noise at the genomic scale. The position effects are significant, altering the mean protein expression level by up to 15 times and expression noise by up to 20 times. DNA replication timing, 3D chromosomal conformation, and several histone modifications are major covariates of position effects. Essential genes are enriched in genomic regions with inherently low expression noise, supporting the hypothesis that chromosomal clustering of essential genes results from selection against their expressional stochasticity. Position effects exhibit significant interactions with promoters. Together, our results suggest that position effects have shaped the evolution of chromosome organization and should inform future genome engineering efforts. PMID- 27185546 TI - Clinical Characteristics and Outcomes of Patients with Amphetamine-Associated Cardiomyopathy in South Auckland, New Zealand. AB - BACKGROUND: Amphetamine-associated cardiomyopathy (AAC) is becoming an increasingly recognised entity. The characteristics and outcomes of these patients are poorly understood. METHODS: Thirty patients admitted with heart failure and echocardiographic evidence of cardiomyopathy between 2005 and 2014 and who had a documented history of amphetamine abuse that was considered an important factor in the causation of their cardiomyopathy were retrospectively identified. RESULTS: Mean age at presentation was 40+/-10 years with a male predominance (n=25, 83%). The majority were of indigenous Maori ethnicity. At presentation, four patients were in cardiogenic shock. Five patients required intensive care unit (ICU) admission for inotropic support and mechanical ventilation. Fifteen had severe left ventricular (LV) dilation (mean LV end diastolic dimension 6.8+/-1.0cm) and all patients had severe LV dysfunction (mean LV ejection fraction 22+/-8%). Despite optimal heart failure therapy, LV size remained significantly dilated with minimal improvement in LV function. During median follow-up of 18 months, five patients died from end-stage heart failure and 17 had at least one readmission with decompensated heart failure. CONCLUSION: Amphetamine-associated cardiomyopathy was seen predominantly in young indigenous Maori men. They presented with severe cardiomyopathy, often requiring ICU admission. Severe LV dilation and significant LV dysfunction persisted despite treatment and mortality was high. PMID- 27185545 TI - The rice thylakoid membrane-bound ascorbate peroxidase OsAPX8 functions in tolerance to bacterial blight. AB - Thylakoid membrane-bound ascorbate peroxidase (tAPX) is a major H2O2-scavenging enzyme. To clarify its functions in tolerance to rice bacterial blight, we produced rice lines overexpressing and suppressing tAPX (OsAPX8). The overexpressing lines exhibited increased tolerance to bacterial pathogen. The RNA interference (RNAi) lines were considerably more sensitive than the control plant. Further analysis of the H2O2 content in these transgenic plants indicated that the H2O2 accumulation of OsAPX8-overexpressing plants was considerably less than that of wild-type and RNAi plants upon challenge with bacterial pathogen. Interestingly, H2O2 was the most important factor for the serious leaf dehydration and withering of rice without major resistance genes and was not the cause of hypersensitivity. It addition, wall tightening or loosening can occur according to the level of H2O2. In addition, OsAPX8 interacted with the susceptibility protein Os8N3/Xa13, and their binding repressed the reaction of OsAPX8 in tolerance to bacterial blight. PMID- 27185548 TI - Temporal interactions of plant - insect - predator after infection of bacterial pathogen on rice plants. AB - Pathogenic infection on plants may affect interactions of host-plants with their herbivores, as well as the herbivores with their predators. In this study, the effects of infection by pathogenic bacterium Xanthomonas oryzae pv. oryzae (Xoo), which causes a vascular disease in rice, on rice plants and consequent interactions with a rice herbivore, brown rice planthopper (BPH) Nilaparvata lugens, and its major predator, Cyrtorhinus lividipennis, were investigated. The results showed that the rice plants exhibited increased resistance to BPH only at 3 d post-inoculation of Xoo, while the Xoo infection did not affect the development and fecundity of BPH. BPH exhibited a higher preference to Xoo infected rice plants, whereas C. lividipennis preferred the Xoo infected rice plants after BPH fed, but preferred healthy rice plants without BPH fed. Volatile organic compounds emitted from Xoo rice were significantly higher than those from healthy rice plants, Xoo infection on BPH fed plants caused rice plants to emit more the herbivore-induced plant volatiles, while all of these changes correlated to the temporal dimension. These results demonstrated that Xoo infection significantly influenced the interactions of rice plants with two non-vectors, BPH and its predator, although these effects exhibited in a temporal pattern after infection. PMID- 27185549 TI - Proteomic profiling reveals dopaminergic regulation of progenitor cell functions of goldfish radial glial cells in vitro. AB - Radial glial cells (RGCs) are stem-like cells found in the developing and adult central nervous system. They function as both a scaffold to guide neuron migration and as progenitor cells that support neurogenesis. Our previous study revealed a close anatomical relationship between dopamine neurons and RGCs in the telencephalon of female goldfish. In this study, label-free proteomics was used to identify the proteins in a primary RGC culture and to determine the proteome response to the selective dopamine D1 receptor agonist SKF 38393 (10MUM), in order to better understand dopaminergic regulation of RGCs. A total of 689 unique proteins were identified in the RGCs and these were classified into biological and pathological pathways. Proteins such as nucleolin (6.9-fold) and ependymin related protein 1 (4.9-fold) were increased in abundance while proteins triosephosphate isomerase (10-fold) and phosphoglycerate dehydrogenase (5-fold) were decreased in abundance. Pathway analysis revealed that proteins that consistently changed in abundance across biological replicates were related to small molecules such as ATP, lipids and steroids, hormones, glucose, cyclic AMP and Ca(2+). Sub-network enrichment analysis suggested that estrogen receptor signaling, among other transcription factors, is regulated by D1 receptor activation. This suggests that these signaling pathways are correlated to dopaminergic regulation of radial glial cell functions. Most proteins down regulated by SKF 38393 were involved in cell cycle/proliferation, growth, death, and survival, which suggests that dopamine inhibits the progenitor-related processes of radial glial cells. Examples of differently expressed proteins including triosephosphate isomerase, nucleolin, phosphoglycerate dehydrogenase and capping protein (actin filament) muscle Z-line beta were validated by qPCR and western blot, which were consistent with MS/MS data in the direction of change. This is the first study to characterize the RGC proteome on a large scale in a vertebrate species. These data provide novel insight into glial protein networks that are associated with neuroendocrine function and neurogenesis in the teleost brain. BIOLOGICAL SIGNIFICANCE: While the role of radial glial cells in organizing brain structure and neurogenesis has been well studied, protein profiling experiments in this unique cell type has not been conducted. This study is the first to profile the proteome of goldfish radial glial cells in culture and to study the regulation of progenitor functions of radial glial cells by the neurotransmitter dopamine. This study provides the foundation for molecular network analysis in fish radial glial cells, and identifies cellular processes and signaling pathways in these cells with roles in neurogenesis and neuroendocrine function. Lastly, this study begins to characterize signatures and biomarkers for specific neuroendocrine and neurogenesis disruptors. PMID- 27185550 TI - Mature forms of the major seed storage albumins in sunflower: A mass spectrometric approach. AB - Seed storage albumins are abundant, water-soluble proteins that are degraded to provide critical nutrients for the germinating seedling. It has been established that the sunflower albumins encoded by SEED STORAGE ALBUMIN 2 (SESA2), SESA20 and SESA3 are the major components of the albumin-rich fraction of the common sunflower Helianthus annuus. To determine the structure of sunflowers most important albumins we performed a detailed chromatographic and mass spectrometric characterization to assess what post-translational processing they receive prior to deposition in the protein storage vacuole. We found that SESA2 and SESA20 each encode two albumins. The first of the two SESA2 albumins (SESA2-1) exists as a monomer of 116 or 117 residues, differing by a threonine at the C-terminus. The second of the two SESA2 albumins (SESA2-2) is a monomer of 128 residues. SESA20 encodes the albumin SESA20-2, which is a 127-residue monomer, whereas SESA20-1 was not abundant enough to be structurally described. SESA3, which has been partly characterized previously, was found in several forms with methylation of its asparagine residues. In contrast to other dicot albumins, which are generally matured into a heterodimer, all the dominant mature sunflower albumins SESA2, SESA20-2, SESA3 and its post-translationally modified analogue SESA3-a are monomeric. BIOLOGICAL SIGNIFICANCE: Sunflower plants have been bred to thrive in various climate zones making them favored crops to meet the growing worldwide demand by humans for protein. The abundance of seed storage proteins makes them an important source of protein for animal and human nutrition. This study explores the structures of the dominant sunflower napin-type seed storage albumins to understand what structures evolution has favored in the most abundant proteins in sunflower seed. PMID- 27185551 TI - Proteomic analysis of outer membrane proteins and vesicles of a clinical isolate and a collection strain of Stenotrophomonas maltophilia. AB - Stenotrophomonas maltophilia is a Gram-negative pathogen with emerging nosocomial incidence that displays a high genomic diversity, complicating the study of its pathogenicity, virulence and resistance factors. The interaction of bacterial pathogens with host cells is largely mediated by outer membrane proteins (OMPs). Indeed, several OMPs of Gram-negative bacteria have been recognized as important virulence factors and targets for host immune recognition or to be involved in mechanisms of resistance to antimicrobials. OMPs are also present in outer membrane vesicles (OMVs), which bacteria constitutively secrete to the extracellular milieu and are essential for bacterial survival and pathogenesis. Here, we report the characterization of the OMP and native OMV subproteomes of a clinical isolate (M30) and a collection strain (ATCC13637) of S. maltophilia. We had previously shown that the ATCC13637 strain has an attenuated phenotype in a zebrafish model of infection, as well as a distinct susceptibility profile against a panel of antimicrobials. The protein profiles of the OMP and OMV subproteomes of these two strains and their differences consequently point at pathogenesis, virulence or resistance proteins, such as two variants of the quorum-sensing factor Ax21 that are found to be highly abundant in the OMP fraction and exported to OMVs. BIOLOGICAL SIGNIFICANCE: Stenotrophomonas maltophilia is rapidly climbing positions in the ranking of multidrug-resistant pathogens that are frequently isolated in hospital environments. Being an emerging human pathogen, the knowledge on the factors determining the pathogenicity, virulence and resistance traits of this microorganism is still scarce. Outer membrane proteins (OMPs) and vesicles (OMVs) are key elements for the interaction of Gram-negative bacteria with their environment -including the host-and have fundamental roles in both infection and resistance processes. The present study sets a first basis for a phenotype-dependent characterisation of the OMP subproteome of S. maltophilia and complements very recent work on the OMV subproteome of this species. The variability found among even two strains demonstrates once more that the analysis of genotypically and phenotypically distinct isolates under various conditions will be required before we can draw a significant picture of the OMP and OMV subproteomes of S. maltophilia. PMID- 27185552 TI - Mortality predictors in recipients developing acute respiratory distress syndrome due to pneumonia after kidney transplantation. AB - BACKGROUND: The aim of the present study was to investigate the risk factors related to hospital mortality due to infection in kidney recipients with ARDS meeting the Berlin definition. METHODS: Univariate and multivariate logistic regression analysis were used to confirm the independent risk factors related to infection-associated mortality. RESULTS: From January 2001 to August 2014, a total of 94 recipients with acute respiratory dress syndrome (ARDS) caused by pneumonia following kidney transplantation were enrolled in the present study. The most common type of infection was bacterial (52/94; 55.3%), viral (25/94; 26.6%), and polymicrobial (14/94; 14.9%). The most common ARDS was diagnosed within 6 months after transplantation (76/94; 80.9%). There were 39 deaths in these recipients (39/94; 41.5%). Eleven (11.7%) patients had mild, 47 (50.0%) moderate, and 36 (38.3%) severe ARDS; mortality was 27.3, 27.7, and 63.9%, respectively. The independent predictors of infection-related mortality were serum creatinine level >1.5 mg/dL at ARDS onset (OR 3.5 (95%CI 1.2-10.1), p = 0.018) and severe ARDS (OR 3.6 (95%CI 1.4-9.7), p = 0.009) in the multivariate analysis. CONCLUSION: Infection-related mortality in kidney transplant patients with ARDS was associated with high serum creatinine level and severe ARDS. PMID- 27185553 TI - Synergistic Effects of Marine Reserves and Harvest Controls on the Abundance and Catch Dynamics of a Coral Reef Fishery. AB - Marine no-take reserves, where fishing and other extractive activities are prohibited, have well-established conservation benefits [1], yet their impacts on fisheries remains contentious [2-4]. For fishery species, reserves are often implemented alongside more conventional harvest strategies, including catch and size limits [2, 5]. However, catch and fish abundances observed post-intervention are often attributed to reserves, without explicitly estimating the potential contribution of concurrent management interventions [2, 3, 6-9]. Here we test a metapopulation model against observed fishery [10] and population [11] data for an important coral reef fishery (coral trout; Plectropomus spp.) in Australia's Great Barrier Reef Marine Park (GBRMP) to evaluate how the combined increase in reserve area [12] and reduction in fishing effort [13, 14] in 2004 influenced changes in fish stocks and the commercial fishery. We found that declines in catch, increases in catch rates, and increases in biomass since 2004 were substantially attributable to the integration of direct effort controls with the rezoning, rather than the rezoning alone. The combined management approach was estimated to have been more productive for fish and fisheries than if the rezoning had occurred alone and comparable to what would have been obtained with effort controls alone. Sensitivity analyses indicate that the direct effort controls prevented initial decreases in catch per unit effort that would have otherwise occurred with the rezoning. Our findings demonstrate that by concurrently restructuring the fishery, the conservation benefits of reserves were enhanced and the fishery cost of rezoning the reserve network was socialized, mitigating negative impacts on individual fishers. PMID- 27185554 TI - The Neural Circuitry that Functions as a Switch for Courtship versus Aggression in Drosophila Males. AB - Courtship and aggression are induced in a mutually exclusive manner in male Drosophila melanogaster, which quickly chooses one of these behavioral repertoires to run depending on whether the encountered conspecific is a female or male, yet the neural mechanism underlying this decision making remains obscure. By targeted excitation and synaptic blockage in a subset of brain neurons, we demonstrate here that the fruitless (fru)-negative subfraction (~20 cells) of a doublesex-positive neural cluster, pC1, acts as the aggression triggering center whereas the fru-positive subfraction (~20 cells) of pC1 acts as the courtship-triggering center, and that the mutually exclusive activation of these two centers is attained by a double-layered inhibitory switch composed of two fru single-positive clusters, LC1 and mAL. To our knowledge, this is the first report to unravel the cellular identity of the neural switch that governs the alternative activation of aggression and courtship in the animal kingdom. PMID- 27185556 TI - Maladaptive Sex Ratio Adjustment in the Invasive Brine Shrimp Artemia franciscana. AB - Sex allocation theory is often hailed as the most successful area of evolutionary theory due to its striking success as a predictor of empirical observations [1]. Most naturally occurring sex ratios can be explained by the principle of equal investment in the sexes [2-4] or by cases of "extraordinary" sex allocation [5]. Deviations from the expected sex ratio are often correlated with weak selection or low environmental predictability (e.g., [6, 7]); true cases of aberrant sex allocation are surprisingly rare [8]. Here, we present a case of long-lasting maladaptive sex allocation, which we discovered in invasive populations of the exclusively sexual brine shrimp Artemia franciscana. A. franciscana was introduced to Southern France roughly 500 generations ago [9]; since then, it has coexisted with the native asexual species Artemia parthenogenetica [10]. Although we expect A. franciscana to produce balanced offspring sex ratios, we regularly observed extremely male-biased sex ratios in invasive A. franciscana, which were significantly correlated to the proportion of asexuals in the overall population. We experimentally proved that both invasive- and native-range A. franciscana overproduced sons when exposed to excess females, without distinguishing between conspecific and asexual females. We conclude that A. franciscana adjust their offspring sex ratio in function of the adult sex ratio but are information limited in the presence of asexual females. Their facultative adjustment trait, which is presumably adaptive in their native range, has thus become maladaptive in the invasive range where asexuals occur. Despite this, it has persisted unchanged for hundreds of generations. PMID- 27185557 TI - A Snapshot-Based Mechanism for Celestial Orientation. AB - In order to protect their food from competitors, ball-rolling dung beetles detach a piece of dung from a pile, shape it into a ball, and roll it away along a straight path [1]. They appear to rely exclusively on celestial compass cues to maintain their bearing [2-8], but the mechanism that enables them to use these cues for orientation remains unknown. Here, we describe the orientation strategy that allows dung beetles to use celestial cues in a dynamic fashion. We tested the underlying orientation mechanism by presenting beetles with a combination of simulated celestial cues (sun, polarized light, and spectral cues). We show that these animals do not rely on an innate prediction of the natural geographical relationship between celestial cues, as other navigating insects seem to [9, 10]. Instead, they appear to form an internal representation of the prevailing celestial scene, a "celestial snapshot," even if that scene represents a physical impossibility for the real sky. We also find that the beetles are able to maintain their bearing with respect to the presented cues only if the cues are visible when the snapshot is taken. This happens during the "dance," a behavior in which the beetle climbs on top of its ball and rotates about its vertical axis [11]. This strategy for reading celestial signals is a simple but efficient mechanism for straight-line orientation. PMID- 27185555 TI - Mechanoaccumulative Elements of the Mammalian Actin Cytoskeleton. AB - To change shape, divide, form junctions, and migrate, cells reorganize their cytoskeletons in response to changing mechanical environments [1-4]. Actin cytoskeletal elements, including myosin II motors and actin crosslinkers, structurally remodel and activate signaling pathways in response to imposed stresses [5-9]. Recent studies demonstrate the importance of force-dependent structural rearrangement of alpha-catenin in adherens junctions [10] and vinculin's molecular clutch mechanism in focal adhesions [11]. However, the complete landscape of cytoskeletal mechanoresponsive proteins and the mechanisms by which these elements sense and respond to force remain to be elucidated. To find mechanosensitive elements in mammalian cells, we examined protein relocalization in response to controlled external stresses applied to individual cells. Here, we show that non-muscle myosin II, alpha-actinin, and filamin accumulate to mechanically stressed regions in cells from diverse lineages. Using reaction-diffusion models for force-sensitive binding, we successfully predicted which mammalian alpha-actinin and filamin paralogs would be mechanoaccumulative. Furthermore, a "Goldilocks zone" must exist for each protein where the actin binding affinity must be optimal for accumulation. In addition, we leveraged genetic mutants to gain a molecular understanding of the mechanisms of alpha actinin and filamin catch-bonding behavior. Two distinct modes of mechanoaccumulation can be observed: a fast, diffusion-based accumulation and a slower, myosin II-dependent cortical flow phase that acts on proteins with specific binding lifetimes. Finally, we uncovered cell-type- and cell-cycle-stage specific control of the mechanosensation of myosin IIB, but not myosin IIA or IIC. Overall, these mechanoaccumulative mechanisms drive the cell's response to physical perturbation during proper tissue development and disease. PMID- 27185558 TI - A Eukaryote without a Mitochondrial Organelle. AB - The presence of mitochondria and related organelles in every studied eukaryote supports the view that mitochondria are essential cellular components. Here, we report the genome sequence of a microbial eukaryote, the oxymonad Monocercomonoides sp., which revealed that this organism lacks all hallmark mitochondrial proteins. Crucially, the mitochondrial iron-sulfur cluster assembly pathway, thought to be conserved in virtually all eukaryotic cells, has been replaced by a cytosolic sulfur mobilization system (SUF) acquired by lateral gene transfer from bacteria. In the context of eukaryotic phylogeny, our data suggest that Monocercomonoides is not primitively amitochondrial but has lost the mitochondrion secondarily. This is the first example of a eukaryote lacking any form of a mitochondrion, demonstrating that this organelle is not absolutely essential for the viability of a eukaryotic cell. PMID- 27185560 TI - Gut Microbiota and Extreme Longevity. AB - The study of the extreme limits of human lifespan may allow a better understanding of how human beings can escape, delay, or survive the most frequent age-related causes of morbidity, a peculiarity shown by long-living individuals. Longevity is a complex trait in which genetics, environment, and stochasticity concur to determine the chance to reach 100 or more years of age [1]. Because of its impact on human metabolism and immunology, the gut microbiome has been proposed as a possible determinant of healthy aging [2, 3]. Indeed, the preservation of host-microbes homeostasis can counteract inflammaging [4], intestinal permeability [5], and decline in bone and cognitive health [6, 7]. Aiming at deepening our knowledge on the relationship between the gut microbiota and a long-living host, we provide for the first time the phylogenetic microbiota analysis of semi-supercentenarians, i.e., 105-109 years old, in comparison to adults, elderly, and centenarians, thus reconstructing the longest available human microbiota trajectory along aging. We highlighted the presence of a core microbiota of highly occurring, symbiotic bacterial taxa (mostly belonging to the dominant Ruminococcaceae, Lachnospiraceae, and Bacteroidaceae families), with a cumulative abundance decreasing along with age. Aging is characterized by an increasing abundance of subdominant species, as well as a rearrangement in their co-occurrence network. These features are maintained in longevity and extreme longevity, but peculiarities emerged, especially in semi-supercentenarians, describing changes that, even accommodating opportunistic and allochthonous bacteria, might possibly support health maintenance during aging, such as an enrichment and/or higher prevalence of health-associated groups (e.g., Akkermansia, Bifidobacterium, and Christensenellaceae). PMID- 27185559 TI - Multiple Time Courses of Vestibular Set-Point Adaptation Revealed by Sustained Magnetic Field Stimulation of the Labyrinth. AB - A major focus in neurobiology is how the brain adapts its motor behavior to changes in its internal and external environments [1, 2]. Much is known about adaptively optimizing the amplitude and direction of eye and limb movements, for example, but little is known about another essential form of learning, "set point" adaptation. Set-point adaptation balances tonic activity so that reciprocally acting, agonist and antagonist muscles have a stable platform from which to launch accurate movements. Here, we use the vestibulo-ocular reflex-a simple behavior that stabilizes the position of the eye while the head is moving to investigate how tonic activity is adapted toward a new set point to prevent eye drift when the head is still [3, 4]. Set-point adaptation was elicited with magneto-hydrodynamic vestibular stimulation (MVS) by placing normal humans in a 7T MRI for 90 min. MVS is ideal for prolonged labyrinthine activation because it mimics constant head acceleration and induces a sustained nystagmus similar to natural vestibular lesions [5, 6]. The MVS-induced nystagmus diminished slowly but incompletely over multiple timescales. We propose a new adaptation hypothesis, using a cascade of imperfect mathematical integrators, that reproduces the response to MVS (and more natural chair rotations), including the gradual decrease in nystagmus as the set point changes over progressively longer time courses. MVS set-point adaptation is a biological model with applications to basic neurophysiological research into all types of movements [7], functional brain imaging [8], and treatment of vestibular and higher-level attentional disorders by introducing new biases to counteract pathological ones [9]. PMID- 27185562 TI - Mitral Stenosis with Extensive Left Atrial Thrombus. PMID- 27185561 TI - Clinical and laboratory correlates of platelet alloimmunization and refractoriness in the PLADO trial. AB - BACKGROUND AND OBJECTIVES: Platelet alloimmunization and refractoriness to platelet transfusion are complications of platelet transfusion therapy. The platelet dose (PLADO) trial, as the largest prospective randomized trial of prophylactic platelet therapy to date, afforded an opportunity to analyse these two issues. MATERIALS AND METHODS: PLADO patient records were examined for evidence of platelet alloimmunization, defined as an increase in HLA Class I panel-reactive antibodies (PRA) to >=20%, and clinical refractoriness, defined as two consecutive <=4 h posttransfusion corrected platelet count increments (CCI) of <5000. Multivariate logistic regression, restricted to platelet-transfused subjects who received exclusively either in-process leucoreduction apheresis or whole blood-derived (WBD) leucocyte-reduced platelets, compared the frequency of these outcomes by platelet unit and patient characteristics. RESULTS: Forty of 816 evaluable platelet-transfused patients (5%) became alloimmunized during the trial. Prior pregnancy, chemotherapy only compared to progenitor cell transplant, and low platelet dose - all were associated with significantly higher rates of alloimmunization. Among 35 alloimmunized patients evaluated for refractoriness, 8 (23%) had two consecutive CCI < 5000/MUl. Regardless of alloimmunization status, CCIs < 5000/MUl were observed following 17% of platelet transfusions. Among 734 patients receiving at least two platelet transfusions, two consecutive CCIs of <=5000 occurred in 102 (14%). CONCLUSIONS: The incidence of new platelet alloimmunization was low in the PLADO study, but follow-up was at most 30 days. Alloimmunization was present in only 8 of 102 (8%) of observed cases of refractoriness, suggesting that other causes of poor posttransfusion increments are frequent. PMID- 27185563 TI - Metastatic low-grade fibromyxoid sarcoma of the broad ligament: A case report and literature review. PMID- 27185565 TI - Scientific rebuttal to a published article "Multiplex Real-Time PCR for identification of Canine Parvovirus antigenic types". PMID- 27185564 TI - Impact of aphid alarm pheromone release on virus transmission efficiency: When pest control strategy could induce higher virus dispersion. AB - Aphids cause serious damages to crops not only by tacking sap but also by transmitting numerous viruses. To develop biological control, the aphid alarm pheromone, namely E-beta-farnesene (EbetaF), has been demonstrated to be efficient to repel aphids and as attract beneficials, making it a potential tool to control aphid pests. Considering aphids also as virus vectors, changes of their behavior could also interfere with the virus acquisition and transmission process. Here, a combination of two aphid species and two potato virus models were selected to test the influence of EbetaF release on aphid and virus dispersion under laboratory conditions. EbetaF release was found to significantly decrease the population of Myzus persicae and Macrosiphum euphorbiae around the infochemical releaser but simultaneously also increasing the dispersal of Potato Virus Y (PVY). At the opposite, no significant difference for Potato Leaf Roll Virus (PLRV) transmission efficiency was observed with similar aphid alarm pheromone releases for none of the aphid species. These results provide some support to carefully consider infochemical releasers not only for push-pull strategy and pest control but also to include viral disease in a the plant protection to aphids as they are also efficient virus vectors. Impact of aphid kinds and transmission mechanisms will be discussed according to the large variation found between persistent and non persistent potato viruses and interactions with aphids and related infochemicals. PMID- 27185566 TI - Robotic pancreaticoduodenectomy and distal pancreatectomy: State of the art. AB - Over recent years, minimally invasive pancreatic resections have increasingly been reported in the literature. Even though pancreatic surgery is still considered a challenge for surgeons due to its technical difficulties and high morbidity, the development and spread of robotic surgery has highlighted a new interest, which has induced a rapid spread of robotic approaches for pancreatic resections. This study presents a systematic review of the literature regarding robotic pancreaticoduodenectomy and distal pancreatectomy in order to assess the safety and feasibility of robotic pancreatic resection. PMID- 27185568 TI - Development of 'Twazon': An Arabic App for Weight Loss. AB - BACKGROUND: Weight gain and its related illnesses have become a major public health issue across the world, with Saudi Arabia and other Gulf countries seeing dramatic increases in obesity and overweight, and yet there is very little information on how to intervene with this demographic due to cultural and linguistic barriers. As the use of smartphones and apps has also increased in the region, information communication technologies could be a cost-effective means of facilitating the delivery of behavior-modification interventions directly to the target population. Although there are existing apps that offer lifestyle modification tools, they do not give consideration to the evidence-based practices for weight management. This offers an opportunity to create an Arabic language weight loss app that offers localized content and adheres to evidence informed practices that are needed for effective weight loss. OBJECTIVE: This paper describes the process of developing an Arabic weight loss app designed to facilitate the modification of key nutritional and physical activity behaviors among Saudi adults, while taking into consideration cultural norms. METHODS: The development of the Twazon app involved: (1) reviewing all available Arabic weight loss apps and compared with evidence-based practices for weight loss, (2) conducting a qualitative study with overweight and obese Saudi women to ascertain their preferences, (3) selecting which behavioral change strategies and guidelines to be used in the app, (4) creating the Saudi Food Database, (5) deciding on graphic design for both iPhone operating system and Android platforms, including user interface, relational database, and programming code, and (6) testing the beta version of the app with health professionals and potential users. RESULTS: The Twazon app took 23 months to develop and included the compilation of an original Saudi Food database. Eight subjects gave feedback regarding the content validity and usability of the app and its features during a pilot study. The predominant issue among the group was the lack of information explaining how to use the app. This has since been resolved through the implementation of a tutorial. No other changes were required to be made. CONCLUSIONS: Information communication technologies, such as smartphone apps, may be an effective tool for facilitating the modification of unhealthy lifestyle habits in Saudi; however, consideration must be given to the target population, cultural norms, and changing trends in the global market. The effectiveness of the app will be better determined during a 6-month intervention with 200 overweight and obese Saudi women. PMID- 27185567 TI - Exposure to organochlorine pesticides and non-Hodgkin lymphoma: a meta-analysis of observational studies. AB - Growing evidence indicates that exposure to organochlorine pesticides (OCPs) could increase non-Hodgkin lymphoma (NHL) risk. However, results from epidemiological studies investigating this association remain controversial. We thus conducted a meta-analysis to quantitatively evaluate the association between OCP exposure and NHL risk. Relevant publications were searched in PubMed, Web of Science, and Embase and identified according to the inclusion criteria. Thirteen studies (6 nested case-control, 1 case-cohort, and 6 case-control) were selected for this meta-analysis. We used odds ratios (ORs) with 95% confidence intervals (CIs) to estimate the relationship between OCPs exposure and NHL risk. The summary OR for included studies was 1.40 (95% CI 1.27 to 1.56). No overall significant heterogeneity in the OR was observed (Ph = 0.253, I(2) = 12.6%). Furthermore, OR estimates in subgroup analyses were discussed, and strong associations were observed for dichlorodiphenyldichloroethylene (DDE, OR = 1.38, 95% CI 1.14 to 1.66), hexachlorocyclohexane (HCH, OR = 1.42, 95% CI 1.08 to 1.87), chlordane (OR = 1.93, 95% CI 1.51 to 2.48), and hexachlorobenzene (HCB, OR = 1.54, 95% CI 1.20 to 1.99). This meta-analysis had suggested that total OCPs of interest was significantly positively associated with NHL risk. PMID- 27185569 TI - Synthesis and Analgesic Properties of Lidocaine Derivatives with Substituted Aminobenzothiazoles. AB - Local anesthetics are the most widely consumed drugs in the practice of medicine which provide a loss of sensation in a certain body part without loss of consciousness or impairment of central control of essential functions. Lidocaine (I) is the most commonly local anaesthetic drug which is widely used in all species due to its fabulous diffusing and penetrating properties as well as prompt onset of surgical analgesia. In this study, new aminobenzothiazole (with many useful biological and pharmacological properties) analogues were synthesized by changing of amine moiety of I. Both acute and chronic pain properties of new compounds (II-VI) were studied by using the tail immersion and formalin tests on mice and the outcomes were compared with control and lidocaine groups. According to the results, aminobenzothiazole derivatives are better candidates than diethylamine group for replacement on amine moiety of I. Also, derivatives with electron-withdrawing groups on this amine (V and VI) could decrease pain better than electron-donating ones (II and III) (specially on position 6 of this amine, II and V) which may be of concern for blockade of specific sodium channels by these new compounds. PMID- 27185570 TI - Inhibition of P-Glycoprotein Mediated Efflux of Paclitaxel by Coumarin Derivatives in Cancer Stem Cells: An In Silico Approach. AB - P-glycoprotein (P-gp) is well known to cause multidrug resistance (MDR) in cancer cells. This MDR leads to cancer recurrence which is a major obstacle in cancer treatment. High P-gp expression has been observed in the population of cancer stem cells (CSCs) having self-renewal potential. Early detection and inhibition of these CSCs is directly beneficial to cancer treatment. In this study coumarin derivatives are used to inhibit efflux process and thereby enhance bioavailability of various drugs like paclitaxel (PTX). This drug is most commonly used for the treatment of cancers of breast, ovary, head and neck. Coumarin derivatives can be used to reduce the growth of breast cancer stem cells through P-gp mediated efflux inhibition and paclitaxel bioavailability enhancement. With the use of computational approaches including molecular docking simulation and pharmacophore study, few coumarin derivatives have been found to be more potential inhibitors of P-gp mediated efflux. Based on high affinity inhibitors, new coumarin derivatives have been designed and docked at active site cavity of P-gps. Some newly designed coumarin derivatives were found to be more potent due to their higher binding affinity towards target protein. The finding that newly designed coumarins can be exploited for inhibition of P-gp mediated efflux in order to enhance paclitaxel bioavailability and can inhibit breast cancer stem cell growth is significant for designing potent anticancer drugs. PMID- 27185571 TI - Efficacy and safety of multiple doses of QGE031 (ligelizumab) versus omalizumab and placebo in inhibiting allergen-induced early asthmatic responses. AB - BACKGROUND: Omalizumab is an established anti-IgE therapy for the treatment of allergic diseases that prevents IgE from binding to its receptor. QGE031 is an investigational anti-IgE antibody that binds IgE with higher affinity than omalizumab. OBJECTIVE: This study compared the effects of QGE031 with those of omalizumab on clinical efficacy, IgE levels, and FcepsilonRI expression in a clinical model of allergic asthma. METHODS: Thirty-seven patients with mild allergic asthma were randomized to subcutaneous omalizumab, placebo, or QGE031 at 24, 72, or 240 mg every 2 weeks for 10 weeks in a double-blind, parallel-group multicenter study. Inhaled allergen challenges and skin tests were conducted before dosing and at weeks 6, 12, and 18, and blood was collected until 24 weeks after the first dose. RESULTS: QGE031 elicited a concentration- and time dependent change in the provocative concentration of allergen causing a 15% decrease in FEV1 (allergen PC15) that was maximal and approximately 3-fold greater than that of omalizumab (P = .10) and 16-fold greater than that of placebo (P = .0001) at week 12 in the 240-mg cohort. Skin responses reached 85% suppression at week 12 in the 240-mg cohort and were maximal at week 18. The top doses of QGE031 consistently suppressed skin test responses among subjects but had a variable effect on allergen PC15 (2-fold to 500-fold change). QGE031 was well tolerated. CONCLUSION: QGE031 has greater efficacy than omalizumab on inhaled and skin allergen responses in patients with mild allergic asthma. These data support the clinical development of QGE031 as a treatment of asthma. PMID- 27185574 TI - Individual patient information to select patients for different radiation techniques. AB - BACKGROUND AND PURPOSE: Proton therapy is an emerging technique in radiotherapy which results in less dose to the normal tissues with similar target dose than photon therapy, the current standard. Patient-level simulation models support better decision making on which patients would benefit most. MATERIALS AND METHODS: A simulation model was developed tracking individual patients' status regarding the primary tumour and multiple complications. As a proof of principle, the model was populated based on information from a cohort of 1013 head and neck cancer patients. Dose-volume parameters for photon and proton radiation treatment plans were then fed into the model to compare outcomes in terms of length and quality of life and select patients that would benefit most. RESULTS: The illustrative model could adequately replicate the outcomes of photon therapy in the cohort. Improvements from proton therapy varied considerably between patients. The model projects medium-term outcomes for specific individuals and determines the benefits of applying proton rather than photon therapy. CONCLUSIONS: While the model needs to be fed with more and especially recent data before being fully ready for use in clinical practice, it could already distinguish between patients with high and low potential benefits from proton therapy. Benefits are highest for patients with both good prognosis and high expected damage to adjacent organs. The model allows for selecting such patients a priori based on patient relevant outcomes. PMID- 27185572 TI - Survival of elderly patients with multiple myeloma-Effect of upfront autologous stem cell transplantation. AB - BACKGROUND: The aim of this study was to determine the value of upfront autologous transplantation (ASCT) in elderly patients (60-79 years) with myeloma. METHODS: We analysed relative survival (RS) of patients diagnosed in 1998-2011 and treated with ASCT within 12 months after diagnosis in Germany (n = 3591; German Registry of Stem Cell Transplantation) and compare RS with survival of myeloma patients diagnosed in the same years in Germany (n = 13,903; population based German Cancer Registries). RESULTS: Utilisation of ASCT has increased rapidly between 2000-2002 and 2009-2011 (60-64years: 7.0-43.0%; 65-69 years: 6.6 23.7%; 70-79 years: 0.4-4.0%). Comparison of 5-year RS of patients from the general German myeloma population who have survived the first year after diagnosis with 5-year RS of patients treated with ASCT revealed higher survival for transplanted patients among all age groups (60-64: 59.2% versus 66.1%; 65-69: 57.4% versus 61.7%; 70-79: 51.0% versus 56.6%). RS increased strongly between 2003-2005 and 2009-2011 for the general German myeloma population (+8.5%) and for patients treated with ASCT (+11.8%). Differences in RS between these groups increased over time from +1.9% higher age-standardised survival in transplanted patients in 2003-2005 to 5.2% higher survival in 2009-2011. CONCLUSION: We conclude that upfront ASCT might be a major contributor to improved survival for elderly myeloma patients in Germany. PMID- 27185573 TI - Phase 1 study of dalotuzumab monotherapy and ridaforolimus-dalotuzumab combination therapy in paediatric patients with advanced solid tumours. AB - AIM: Dalotuzumab is a highly specific, humanised immunoglobulin G1 monoclonal antibody against insulin-like growth factor receptor 1. This multicenter phase 1 study (NCT01431547) explored the safety and pharmacokinetics of dalotuzumab monotherapy (part 1) and the combination of dalotuzumab with the mammalian target of rapamycin inhibitor ridaforolimus (part 2) in paediatric patients with advanced solid tumours. METHODS: Dalotuzumab was administered intravenously every 3 weeks starting at 900 mg/m(2) and escalating to 1200 and 1500 mg/m(2). Combination therapy included intravenous dalotuzumab at the defined single-agent recommended phase 2 dose (RP2D) and oral ridaforolimus 28 mg/m(2) daily (days 1 5), repeated weekly. Pharmacokinetic studies were performed to evaluate the mean serum trough dalotuzumab concentration, which guided the RP2D. RESULTS: Twenty four patients were enrolled (part 1, n = 20; part 2, n = 4). No dose-limiting toxicities were observed in patients receiving dalotuzumab alone. One patient experienced dose-limiting stomatitis in the combination arm. Pharmacokinetic data showed dose-dependent increases in exposure (area under the curve from zero to infinity [AUC0-infinity]) (87,900, 164,000, and 186,000 h*mg/ml for the 900, 1200, and 1500 mg/m(2) dose levels, respectively), maximum serum concentration (Cmax) (392, 643, and 870 mg/ml), and serum trough concentration (Ctrough) (67.1, 71.6, and 101 mg/ml). The mean half-life was 265, 394, and 310 h, respectively. Dalotuzumab pharmacokinetics were not affected by coadministration with ridaforolimus. One of six patients with Ewing sarcoma had confirmed partial response to dalotuzumab monotherapy at 900 mg/m(2). Time to response was 41 d, and progression occurred at 126 d. CONCLUSION: Dalotuzumab was well tolerated in paediatric patients with advanced solid malignancies. The RP2D of dalotuzumab is 900 mg/m(2) (ClinicalTrials.gov identifier: NCT01431547, Protocol PN062). PMID- 27185575 TI - Jurassic zircons from the Southwest Indian Ridge. AB - The existence of ancient rocks in present mid-ocean ridges have long been observed but received less attention. Here we report the discovery of zircons with both reasonably young ages of about 5 Ma and abnormally old ages of approximate 180 Ma from two evolved gabbroic rocks that were dredged from the Southwest Indian Ridge (SWIR) in the Gallieni fracture zone. U-Pb and Lu-Hf isotope analyses of zircons were made using ion probe and conventional laser abrasion directly in petrographic thin sections. Young zircons and their host oxide gabbro have positive Hf isotope compositions (epsilonHf = +15.7-+12.4), suggesting a highly depleted mantle beneath the SWIR. The spread epsilonHf values (from-2.3 to-4.5) of abnormally old zircons, together with the unradiogenic Nd-Hf isotope of the host quartz diorite, appears to suggest an ancient juvenile magmatism along the rifting margin of the southern Gondwana prior to the opening of the Indian Ocean. A convincing explanation for the origin of the unusually old zircons is yet to surface, however, an update of the theory of plate tectonics would be expected with continuing discovery of ancient rocks in the mid-oceanic ridges and abyssal ocean basins. PMID- 27185576 TI - Lateral habenula as a link between thyroid and serotoninergic system modiates depressive symptoms in hypothyroidism rats. AB - Depression-like behavior is observed in both rats and people with hypothyroidism, which suggests that altered thyroid hormone levels are closely associated with mental illness. Furthermore, decreased serotonin (5-hydroxytryptamine, 5-HT) levels are found in some brain regions of hypothyroid rats with depression-like behavior. However, the mechanism underlying the effects of hypothyroidism on the central serotonin system is unclear. The lateral habenula (LHb) is related to both the serotonin and thyroid systems and also plays an important role in the pathogenesis of depression. Our study aimed to disclose the role of the LHb in the onset of depression-like behavior in thyroidectomy (TD) rats. Forced swimming (FST) and open-field tests (OFT) were performed to measure behavioral changes in TD rats. The expression of beta calmodulin-dependent protein kinase type II (beta CaMKII) in the LHb, cytochrome C oxidase (COX) activity in the LHb and dorsal raphe nucleus (DRN), and 5-HT levels in the DRN were assayed. We found that TD rats exhibited depression-like behavior in the FST and OFT. Compared with the sham group, neural activity and the expression of beta CaMKII in TD rats were higher in the LHb, and neural activity and 5-HT levels were lower in the DRN. Depressive behavior and decreased 5-HT levels in the DRN in TD rats were reversed by LHb lesioning. Our study indicates that depression-like behavior in TD rats can be attributed to decreased 5-HT levels in the DRN resulting from inhibition by an overactive LHb. The LHb mediates the effect of the thyroid system on 5-HT function in the DRN. PMID- 27185577 TI - Loss of ubiquitin E2 Ube2w rescues hypersensitivity of Rnf4 mutant cells to DNA damage. AB - SUMO and ubiquitin play important roles in the response of cells to DNA damage. These pathways are linked by the SUMO Targeted ubiquitin Ligase Rnf4 that catalyses transfer of ubiquitin from a ubiquitin loaded E2 conjugating enzyme to a polySUMO modified substrate. Rnf4 can functionally interact with multiple E2s, including Ube2w, in vitro. Chicken cells lacking Rnf4 are hypersensitive to hyroxyurea, DNA alkylating drugs and DNA crosslinking agents, but this sensitivity is suppressed by simultaneous depletion of Ube2w. Cells depleted of Ube2w alone are not hypersensitive to the same DNA damaging agents. Similar results were also obtained in human cells. These data indicate that Ube2w does not have an essential role in the DNA damage response, but is deleterious in the absence of Rnf4. Thus, although Rnf4 and Ube2w functionally interact in vitro, our genetic experiments indicate that in response to DNA damage Ube2w and Rnf4 function in distinct pathways. PMID- 27185578 TI - Head impact in a snowboarding accident. AB - To effectively prevent sport traumatic brain injury (TBI), means of protection need to be designed and tested in relation to the reality of head impact. This study quantifies head impacts during a typical snowboarding accident to evaluate helmet standards. A snowboarder numerical model was proposed, validated against experimental data, and used to quantify the influence of accident conditions (speed, snow stiffness, morphology, and position) on head impacts (locations, velocities, and accelerations) and injury risk during snowboarding backward falls. Three hundred twenty-four scenarios were simulated: 70% presented a high risk of mild TBI (head peak acceleration >80 g) and 15% presented a high risk of severe TBI (head injury criterion >1000). Snow stiffness, speed, and snowboarder morphology were the main factors influencing head impact metrics. Mean normal head impact speed (28 +/- 6 km/h) was higher than equivalent impact speed used in American standard helmet test (ASTM F2040), and mean tangential impact speed, not included in standard tests, was 13.8 (+/-7 km/h). In 97% of simulated impacts, the peak head acceleration was below 300 g, which is the pass/fail criteria used in standard tests. Results suggest that initial speed, impacted surface, and pass/fail criteria used in helmet standard performance tests do not fully reflect magnitude and variability of snowboarding backward-fall impacts. PMID- 27185579 TI - Using avatars to win the fight over BRAF inhibitor resistance. PMID- 27185580 TI - A change in temporal organization of fidgety movements during the fidgety movement period is common among high risk infants. AB - AIM: General movement assessment (GMA) at 9-20 weeks post-term, can effectively predict cerebral palsy. Our aim was to evaluate intra-individual variability of the temporal organization of fidgety movements (FMs) in high risk infants. MATERIAL AND METHODS: 104 High risk infants (66 males) with at least two video recordings from the FMs period participated. 45 of the infants had GA <28 weeks and/or BW <=800 g. Mean post-term age at first and second assessments was 11.0 (8 16) and 14.0 (11-17) weeks, respectively, and median time-difference between the assessments was 2.0 (range: three days to six weeks) weeks. Video recordings were analyzed according to Prechtl's GMA. RESULTS: 33 (32%) Infants were classified differently at first and second assessments. Six infants (6%) changed from normal to abnormal, and 10 (10%) changed from abnormal to normal FMs. Seven of the ten who changed classification from abnormal to normal were born before GA 26 weeks. A change between intermittent and continual, which are both considered normal, was observed in 17 (16%) infants. CONCLUSION: A change in temporal organization of FMs is common in high risk infants. Especially in extremely preterm infants with abnormal FMs, more than one assessment should be performed before long-term prognosis is considered. PMID- 27185581 TI - Acute renal failure unmasking Lesch-Nyhan disease in a patient with tuberous sclerosis complex. AB - CASE REPORT: We report on a male patient with Tuberous Sclerosis Complex (TSC), which was prenatally diagnosed. At the age of 3 months the patient developed acute renal failure with excessive hyperuricemia. Kidney function improved after rehydration and application of rasburicase, however without full recovery. Due to the inappropriate high levels of uric acid compared to kidney function, screening of hypoxanthine-guanine phosphoribosyltransferase (HPRT) related diseases was initiated. Mutation analysis revealed a deletion of exon 2 and 3 of the HPRT gene confirming the diagnosis of Lesch-Nyhan Disease (LND). After initiation of allopurinol therapy renal function further improved. In the following months the patient developed clinically a typical neurological phenotype of LND and TSC with seizures, severe dystonia and developmental delay. CONCLUSION: Acute renal failure is a rare complication of HPRT related diseases. Combination of two inherited diseases may lead to a delayed diagnosis due to a mixed and maybe misleading phenotype. PMID- 27185582 TI - Clinical development of TargomiRs, a miRNA mimic-based treatment for patients with recurrent thoracic cancer. AB - miRNAs are responsible for post-transcriptional control of gene expression, and are frequently downregulated in cancer. It has become well established that restoring miRNA levels can inhibit tumor growth, and many studies have demonstrated this in preclinical models. This in turn has led to the first clinical trials of miRNA replacement therapy. This special report focuses on the development of TargomiRs - miRNA mimics delivered by targeted bacterial minicells - and the very first clinical experience of a miRNA replacement therapy in thoracic cancer patients in the Phase I MesomiR-1 trial. PMID- 27185585 TI - Nitrogen-Doped Ordered Mesoporous Anatase TiO2 Nanofibers as Anode Materials for High Performance Sodium-Ion Batteries. AB - Nitrogen-doped ordered mesoporous TiO2 nanofibers (N-MTO) have been fabricated by electrospinning and subsequent nitridation treatment. The N-doping in TiO2 leads to the formation of Ti(3+) , resulting in the improved electron conductivity of TiO2 . In addition, one-dimensional (1D) N-MTO nanostructure possesses very short diffusion length of Na(+) /e(-) in N-MTO, easy access of electrolyte, and high conductivity transport of electrons along the percolating fibers. The N-MTO shows excellent sodium storage performance. PMID- 27185583 TI - Stimuli-Regulated Enzymatically Degradable Smart Graphene-Oxide-Polymer Nanocarrier Facilitating Photothermal Gene Delivery. AB - Graphene oxide (GO) has attracted huge interest in the area of biomedical application due to its unique physicochemical properties, but the issue of long term toxicity in the body remains unclear. Here, the rationally designed GO nanocarriers (ssPEG-PEI-GO) modified with polyethylene glycol (PEG) and branched polyethylenimine (BPEI) via disulfide linkage are described to control the biological activity of GO as a delivery carrier and its degradation in biological systems. The ssPEG-PEI-GO efficiently interacts with plasmid DNA (pDNA) to form a stable nanocomplex by electrostatic interaction. After cellular uptake, ssPEG-PEI GO/pDNA complex can easily escape from endosomes by photothermal conversion of GO upon near-infrared irradiation and subsequent photothermally induced endosome disruption. After endosomal escape, reducing intracellular environment enables polymer dissociation and rapid gene release and therefore shows enhanced gene transfection efficiency with low toxicity in comparison with non-reducible amide functionalized GO nanocarriers (amPEG-PEI-GO) and control BPEIs. Besides, dePEGylated GO nanocarrier, owing to its disulfide bond, exhibits higher entrapment by macrophages compared with amide-functionalized one and subsequently degrades in macrophage. The degradation process can be monitored by photoluminescence emitted from degraded GO. These results suggest new directions in the design of biodegradable and multifunctional GO-based nanocarrier for biomedical application. PMID- 27185584 TI - From glycals to aminosugars: a challenging test for new stereoselective aminohydroxylation and related methodologies. AB - The introduction of amino functionalities in a regio- and stereoselective manner onto sugar scaffolds represents a great challenge in carbohydrate synthesis. The most relevant methods to access 1-, 2-, 3-amino or 1,2-diaminosugars starting from glycals and 2,3-hexenopyranosides derived from them are concisely reviewed. The main synthetic strategies for accessing this class of compounds are classified in intermolecular and intramolecular approaches and the key features of each class are discussed. This review highlights how carbohydrate derivatives always pose great challenges representing a benchmark for assessing the efficiency of stereoselective strategies, and aims to give the readers inspiration for the development of new procedures. PMID- 27185586 TI - A new occurrence of ambient inclusion trails from the ~1900-million-year-old Gunflint Formation, Ontario: nanocharacterization and testing of potential formation mechanisms. AB - Ambient inclusion trails (AITs) are tubular microstructures thought to form when a microscopic mineral crystal is propelled through a fine-grained rock matrix. Here, we report a new occurrence of AITs from a fossilized microbial mat within the 1878-Ma Gunflint Formation, at Current River, Ontario. The AITs are 1-15 MUm in diameter, have pyrite as the propelled crystal, are infilled with chlorite and have been propelled through a microquartz (chert) or chlorite matrix. AITs most commonly originate at the boundary between pyrite- and chlorite-rich laminae and chert-filled fenestrae, with pyrite crystals propelled into the fenestrae. A subset of AITs originate within the fenestrae, rooted either within the chert or within patches of chlorite. Sulphur isotope data ((34) S/(32) S) obtained in situ from AIT pyrite have a delta(34) S of -8.5 to +8.0 0/00, indicating a maximum of ~30 0/00 fractionation from Palaeoproterozoic seawater sulphate (delta(34) S ~ +20 0/00). Organic carbon is common both at the outer margins of the fenestrae and in patches of chlorite where most AITs originate, and can be found in smaller quantities further along some AITs towards the terminal pyrite grain. We infer that pyrite crystals now found within the AITs formed via the action of heterotrophic sulphate-reducing bacteria during early diagenesis within the microbial mat, as pore waters were becoming depleted in seawater sulphate. Gases derived from this process such as CO2 and H2 S were partially trapped within the microbial mat, helping produce birds-eye fenestrae, while rapid microquartz precipitation closed porosity. We propose that propulsion of the pyrite crystals to form AITs was driven by two complementary mechanisms during burial and low grade metamorphism: firstly, thermal decomposition of residual organic material providing CO2 , and potentially CH4 , as propulsive gases, plus organic acids to locally dissolve the microquartz matrix; and secondly, reactions involving clay minerals that potentially led to enhanced quartz solubility, plus increases in fluid and/or gas pressure during chlorite formation, with chlorite then infilling the AITs. This latter mechanism is novel and represents a possible way to generate AITs in environments lacking organic material. PMID- 27185587 TI - Safe MRI-Compatible electrical muscle stimulation (EMS) system. AB - PURPOSE: To develop an inexpensive magnetic resonance imaging (MRI)-compatible electrical muscle stimulation (EMS) unit and test it for safety and efficacy. MATERIALS AND METHODS: A simple MRI-compatible EMS device was developed using radiofrequency (RF) translucent electrodes at 3T. RF heating concerns were assessed using optical temperature measurements at electrode sites, during scanning of a phantom. EMS efficacy and consistency was investigated through in vivo (n = 5) measures of 31 P-MRS phosphocreatine (PCr) reduction, and altered blood oxygen level-dependent (BOLD) signal and the results were compared to effects from equivalent voluntary effort on the same subjects. RESULTS: The presence of an EMS pulse did not interfere with the T2 * signal in a phantom. However, signal-to-noise ratio (SNR) was reduced by 70% at electrode sites, but only by 10% 4 cm distally. Under RF intense conditions, the temperature at the electrode site increased by only 4.7 degrees C over a 16-minute time span. In vivo muscle stimulation resulted in 13.5 +/- 1.8% reduction in PCr, which was not significantly (P < 0.195) different from voluntary contraction. Reproducible muscle BOLD signal changes following EMS were noted, with a maximal increase of 10.0 +/- 2.6% seen in the central soleus. For soleus and gastrocnemius compartments, EMS produced significantly higher BOLD signal change compared to voluntary contraction (P < 0.05). CONCLUSION: A safe and inexpensive MRI compatible EMS unit can be easily built for evaluating muscle function and metabolism within a 3T MRI scanner. Clinical applications might include evaluating skeletal muscle function in patients with limited or absent voluntary skeletal motor function or inadequate exercise capacity. J. Magn. Reson. Imaging 2016;44:1530-1538. PMID- 27185588 TI - Synthesis and structure-property relationships of phthalimide and naphthalimide based organic pi-conjugated small molecules. AB - Five organic pi-conjugated small molecules with bithiophene-phthalimide backbones bearing alkyl chains of different symmetry, length and branching character were synthesized using optimized microwave and direct heteroarylation protocols. The chosen alkyl chains were 1-ethylpropyl, 1-methylbutyl, pentyl, hexyl and octyl. A sixth compound was also synthesized replacing the phthalimide terminal units with octylnaphthalimide for additional scope. Through the thorough analysis of both thermal and optical properties and the investigation of self-assembly tendencies by single crystal X-ray diffraction and variable angle spectroscopic ellipsometry it is evident that alkyl side chains and building block size influence many facets of material properties. Within this class of materials the 1-ethylpropyl derivative exhibited the most unique behaviour. PMID- 27185591 TI - Genomic selection in domestic animals: Principles, applications and perspectives. AB - The principles of genomic selection are described, with the main factors affecting its efficiency and the assumptions underlying the different models proposed. The reasons of its fast adoption in dairy cattle are explained and the conditions of its application to other species are discussed. Perspectives of development include: selection for new traits and new breeding objectives; adoption of more robust approaches based on information on causal variants; predictions of genotype*environment interactions. PMID- 27185590 TI - Genetic and epigenetic variation of human populations: An adaptive tale. AB - The evolutionary history of modern humans means much more than their demographic past. It includes the way in which humans have had to genetically adapt to the different environments they have encountered-nutritional, climatic or pathogenic as well as the different epigenetic responses elicited by such environmental cues. Detecting how natural selection has affected human genome variability has proven to be a powerful tool to delineate genes and biological functions having played a key role in human adaptation, a variation which can also be involved in phenotypes of medical relevance. This article reviews several examples that illustrate well how different environmental pressures, particularly those imposed by pathogens and infectious diseases, have shaped the patterns of genetic and epigenetic variability currently observed in human populations. PMID- 27185592 TI - Calpain-1 and calpain-2 play opposite roles in retinal ganglion cell degeneration induced by retinal ischemia/reperfusion injury. AB - Calpain has been shown to be involved in neurodegeneration, and in particular in retinal ganglion cell (RGC) death resulting from increased intraocular pressure (IOP) and ischemia. However, the specific roles of the two major calpain isoforms, calpain-1 and calpain-2, in RGC death have not been investigated. Here, we show that calpain-1 and calpain-2 were sequentially activated in RGC dendrites after acute IOP elevation. By combining the use of a selective calpain-2 inhibitor (C2I) and calpain-1 KO mice, we demonstrated that calpain-1 activity supported survival, while calpain-2 activity promoted cell death of RGCs after IOP elevation. Calpain-1 activation cleaved PH domain and leucine-rich repeat protein phosphatase 1 (PHLPP1) and activated the Akt pro-survival pathway, while calpain-2 activation cleaved striatal-enriched protein tyrosine phosphatase (STEP) and activated STEP-mediated pro-death pathway in RGCs after IOP elevation. Systemic or intravitreal C2I injection to wild-type mice 2h after IOP elevation promoted RGC survival and improved visual function. Our data indicate that calpain-1 and calpain-2 play opposite roles in high IOP-induced ischemic injury and that a selective calpain-2 inhibitor could prevent acute glaucoma-induced RGC death and blindness. PMID- 27185593 TI - Environmental enrichment imparts disease-modifying and transgenerational effects on genetically-determined epilepsy and anxiety. AB - INTRODUCTION: The absence epilepsies are presumed to be caused by genetic factors, but the influence of environmental exposures on epilepsy development and severity, and whether this influence is transmitted to subsequent generations, is not well known. We assessed the effects of environmental enrichment on epilepsy and anxiety outcomes in multiple generations of GAERS - a genetic rat model of absence epilepsy that manifests comorbid elevated anxiety-like behaviour. METHODS: GAERS were exposed to environmental enrichment or standard housing beginning either prior to, or after epilepsy onset, and underwent EEG recordings and anxiety testing. Then, we exposed male GAERS to early enrichment or standard housing and generated F1 progeny, which also underwent EEG recordings. Hippocampal CRH mRNA expression and DNA methylation were assessed using RT-PCR and pyrosequencing, respectively. RESULTS: Early environmental enrichment delayed the onset of epilepsy in GAERS, and resulted in fewer seizures in adulthood, compared with standard housed GAERS. Enrichment also reduced the frequency of seizures when initiated in adulthood. Anxiety levels were reduced by enrichment, and these anti-epileptogenic and anxiolytic effects were heritable into the next generation. We also found reduced expression of CRH mRNA in GAERS exposed to enrichment, but this was not due to changes in DNA methylation. CONCLUSIONS: Environmental enrichment produces disease-modifying effects on genetically determined absence epilepsy and anxiety, and these beneficial effects are transferable to the subsequent generation. Reduced CRH expression was associated with these phenotypic improvements. Environmental stimulation holds promise as a naturalistic therapy for genetically determined epilepsy which may benefit subsequent generations. PMID- 27185594 TI - The role of BDNF in Alzheimer's disease. PMID- 27185596 TI - Predicting cardiovascular disease. PMID- 27185595 TI - Detrimental effects of oxidative losses in parkin activity in a model of sporadic Parkinson's disease are attenuated by restoration of PGC1alpha. AB - Loss of parkin E3 ligase activity as a result of parkin gene mutation in rare familial forms of Parkinson's disease (PD) has been shown to be detrimental to mitochondrial function and to contribute to ensuing neurodegeneration. This has been shown by ourselves and others to be in part due to reductions in parkin mediated ubiquitination of the transcriptional repressor PARIS, limiting the protein's subsequent degradation by the proteasome. Subsequent elevations in PARIS protein levels result in reduced expression of the master mitochondrial regulator PGC-1alpha, impacting in turn on mitochondrial function. Here, we report that oxidatively-mediated reductions in parkin solubility and function in a mouse model of age-related sporadic PD coincides with increased PARIS levels and reduced PGC-1alpha signaling. Furthermore, restoration of PGC-1alpha expression was found to abrogate losses in mitochondrial function and degeneration of dopaminergic (DAergic) neurons within the substantia nigra pars compacta (SNpc) associated with this particular model. These findings suggest that the PGC-1alpha signaling pathway constitutes a viable therapeutic target for the treatment of not only familial PD, but also more common sporadic forms of the disorder. PMID- 27185597 TI - Photosynthetic acclimation, vernalization, crop productivity and 'the grand design of photosynthesis'. AB - Daniel Arnon first proposed the notion of a 'grand design of photosynthesis' in 1982 to illustrate the central role of photosynthesis as the primary energy transformer for all life on Earth. However, we suggest that this concept can be extended to the broad impact of photosynthesis not only in global energy transformation but also in the regulation of plant growth, development, survival and crop productivity through chloroplast redox signalling. We compare and contrast the role of chloroplast redox imbalance, measured as excitation pressure, in governing acclimation to abiotic stress and phenotypic plasticity. Although all photoautrophs sense excessive excitation energy through changes in excitation pressure, the response to this chloroplast redox signal is species dependent. Due to a limited capacity to adjust metabolic sinks, cyanobacteria and green algae induce photoprotective mechanisms which dissipate excess excitation energy at a cost of decreased photosynthetic performance. In contrast, terrestrial, cold tolerant plants such as wheat enhance metabolic sink capacity which leads to enhanced photosynthetic performance and biomass accumulation with minimal dependence on photoprotection. We suggest that the family of nuclear C repeat binding transcription factors (CBFs) associated with the frost resistance locus, FR2, contiguous with the vernalization locus,VRN1, and mapped to chromosome 5A of wheat, may be critical components that link leaf chloroplast redox regulation to enhanced photosynthetic performance, the accumulation of growth-active gibberellins and the dwarf phenotype during cold acclimation prior to the vegetative to reproductive transition controlled by vernalization in winter cereals. Further genetic, molecular and biochemical research to confirm these links and to elucidate the molecular mechanism by which chloroplast redox modulation of CBF expression leads to enhanced photosynthetic performance is required. Because of the superior abiotic stress tolerance of cold tolerant winter wheat and seed yields that historically exceed those of spring wheat by 30 40%, we discuss the potential to exploit winter cereals for the maintenance or perhaps even the enhancement of cereal productivity under future climate change scenarios that will be required to feed a growing human population. PMID- 27185598 TI - Bioinformatics microarray analysis and identification of gene expression profiles associated with cirrhotic liver. AB - Cirrhosis is the endpoint of liver fibrosis that is accompanied by limited regeneration capacity and complications and is the ultimate cause of death in many patients. Despite this, few studies have thoroughly looked at the gene expression profiles in the cirrhotic liver. Hence, this study aims to identify the genes that were differentially expressed in the cirrhotic liver and to explore the putative related signaling pathway and interaction networks. The gene expression profiles of cirrhotic livers and noncirrhotic livers were examined and compared using microarray gene analysis. Proteins encoded by the differentially expressed genes were analyzed for functional clustering and signaling pathway involvement using MetaCore bioinformatics analyses. The Gene Ontology analysis as well as the Kyoto encyclopedia of Genes and Genomes pathway analysis were also performed. A total of 213 significant genes were differentially expressed at more than a two-fold change in cirrhotic livers as compared to noncirrhotic livers. Of these, 105 upregulated genes and 63 downregulated genes were validated through MetaCore bioinformatics analyses. The signaling pathways and major functions of proteins encoded by these differentially expressed genes were further analyzed; results showed that the cirrhotic liver has a unique gene expression pattern related to inflammatory reaction, immune response, and cell growth, and is potentially cancer related. Our findings suggest that the microarray analysis may provide clues to the molecular mechanisms of liver cirrhosis for future experimental studies. However, further exploration of areas regarding therapeutic strategy might be possible to support metabolic activity, decrease inflammation, or enhance regeneration for liver cirrhosis. PMID- 27185599 TI - Pharmacokinetic study of eplerenone in rats after long-term coadministration with buckwheat tea. AB - The aim of this study was to investigate the effect of long-term intake of Tartary buckwheat tea on the pharmacokinetics (PK) of eplerenone in rats. A validated high-performance liquid chromatography-mass spectrometry (HPLC-MS) method was established to determine the eplerenone in plasma, and the portal vein absorption model was applied to conduct the pharmacokinetic study. Two groups of animals-buckwheat tea group and control group-were involved in this study. Plasma samples were obtained at different time points after administration, and were separated on Shimadzu HPLC-MS 2020 instruments. The method showed good linearity (r=0.9988) over a wide dynamic range (0.20-50 MUg/mL). Within- and between-batch precisions ranged from 2.13% to 7.90%. The extraction recovery rates ranged from 91.96% to 94.96%. The data showed that in the Tartarian buckwheat group the area under the curve and maximum concentration of eplerenone were reduced compared with those of the blank group (p<0.01), but the time to reach peak concentrations of eplerenone (p<0.01) was prolonged. The results suggested that long-term consumption of Tartary buckwheat tea might induce the activities of the hepatic drug metabolizing enzyme, which can accelerate the metabolism of eplerenone. According to the results, the dosage of eplerenone should be adjusted in hypertension treatment trials when administered with Tartary buckwheat or Tartary buckwheat-containing dietary supplements to avoid potential drug interactions. PMID- 27185600 TI - Impact of remaining kidney volume to body weight ratio on renal function in living kidney donors. AB - To investigate whether the ratio of remnant kidney volume to body weight (V/W ratio) can impact renal function in donors, 45 living kidney donors were enrolled. Kidney volume was analyzed by magnetic resonance imaging. Renal function was compared between donors with a V/W ratio of < 2.0 mL/kg (n = 23) or >= 2.0 mL/kg (n = 22). Donors in both V/W groups showed similar serum creatinine levels and estimated glomerular filtration rates (eGFRs) at 7 days and 1 year, whereas donors with a V/W ratio of < 2.0 mL/kg had significantly higher 24-hour urine protein levels at 1 year (0.54 +/- 0.23 g/d vs. 0.33 +/- 0.19 g/d, p = 0.028). Multivariate analysis revealed no correlation between the V/W ratio and eGFR at 7 days or 1 year, and a V/W ratio of < 2 mL/kg was not associated with an increased incidence of eGFR < 60 mL/min/1.73 m(2) at 1 year (risk ratio 1.73, 95% confidence interval 0.10-29.47). The V/W ratio correlated inversely with 24-hour urine protein (r = -0.377, p = 0.021) at 1 year, and donors with a V/W ratio of < 2.0 mL/kg were more likely to show 24-hour urine protein >300 mg (risk ratio 1.70, 95% confidence interval 1.08-2.67) at 1 year. Donors with lower V/W ratios have higher 24-hour urinary protein levels at 1 year after transplantation. These findings suggest that the V/W ratio may be useful for kidney selection. PMID- 27185601 TI - Outcomes and prognostic factors of simple partial cystectomy for localized bladder urothelial cell carcinoma. AB - Radical cystectomy has remained the gold standard for recurrent superficial or muscle invasive bladder tumor. However, partial cystectomy still has a role in those who reject or have contraindications for radical cystectomy. In this study, we sought to identify predictors of bladder recurrence and overall survival after simple partial cystectomy. We included 27 patients with bladder tumor who received simple partial cystectomy without pelvic lymph node dissection between March 2000 and September 2013. Adjuvant chemotherapy or radiation therapy was prescribed according to the pathological results. Parameters were compared on the basis of bladder recurrence and overall survival. During a mean follow-up time of 39 months, five patients (18.5%) experienced bladder recurrence. An older age, a higher pathological stage, positive surgical margins, and distant metastases were significant predictors of overall survival (p = 0.031, p = 0.001, p = 0.001, and p = 0.011, respectively). Meanwhile, previous bladder instillation and positive surgical margins were significant predictors of bladder recurrence (p = 0.026 and p = 0.027, respectively). The rate of consecutive distant metastases (33.3%) was almost twice the rate of bladder recurrence (18.5%), and six patients developed consecutive distant metastases without first experiencing bladder recurrence. In patients who received a simple partial cystectomy as an alternative treatment, previous bladder instillation and positive surgical margins were significant predictors of bladder recurrence. Patients with an older age, positive surgical margins, and consecutive distant metastases had worse overall survival. Partial cystectomy with routine lymph node dissection may be a better option for achieving favorable long-term outcomes. PMID- 27185602 TI - Associated factors in Streptococcus bovis bacteremia and colorectal cancer. AB - Reports suggest that between 25% and 80% of patients with Streptococcus bovis/gallolyticus bacteremia have concomitant colorectal tumors. This retrospective study was aimed to identify associations between clinical characteristics and a finding of colorectal neoplasm in patients with S. bovis bacteremia who had colonoscopy examination. We retrospectively reviewed the records of patients with S. bovis bacteremia from Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, between January 2004 and January 2014. Clinical data including age, sex, comorbidities, blood culture, and colonoscopy findings were collected and their relationship to a finding of colorectal cancer was examined. A total of 107 patients with S. bovis bacteremia were identified, of whom 49 (72% male; age 65 +/- 12 years) were investigated with colonoscopy; 15 of these patients (30.6%) had colorectal adenocarcinoma. Female sex (p = 0.014) and a history of noncolorectal malignancy (p = 0.004) were associated with a finding of colorectal adenocarcinoma. There were no associations with age, percentage of blood cultures, or the presence of diabetes mellitus, chronic liver disease, heart disease, or end-stage renal disease. Our results show that S. bovis bacteremia is associated with the presence of colorectal adenocarcinoma, especially in female patients, and concomitant existence of other malignancies. PMID- 27185604 TI - Clinical experiences of dynamic stabilizers: Dynesys and Dynesys top loading system for lumbar spine degenerative disease. AB - Dynesys (Dynamic Neutralization System) was designed to overcome the shortcomings of fusion. The Dynesys top loading (DTL) system is a new alternative Dynesys system that can be applied via a minimally invasive procedure. This study aimed to ascertain whether DTL is a suitable device for motion preservation and prevention of instability, and to compare the clinical and radiological outcomes between DTL and Dynesys. In this study, 12 patients were treated with Dynesys and 21 patients were treated with DTL. Back and leg pain were evaluated using the visual analog scale. The Oswestry Disability Index was used to evaluate the patients' function. Range of motion (ROM) at the operative level and for the whole lumbar spine was measured pre- and postoperatively. The length of wound, blood loss, length of hospital stay, and operation duration were also compared. All patients were followed up for 12-76 months. Scores on the visual analog scale and Oswestry Disability Index were significantly improved postoperatively. The median ROM of the whole spine and index level ROM in all patients showed 12.5% and 79.6% loss, respectively. The DTL group exhibited significantly better results in terms of blood loss, wound length, and operation duration, in addition to early ambulation. In conclusion, Dynesys and DTL are semirigid fixation systems that can significantly improve clinical symptoms and signs. Our results suggested that DTL was better than Dynesys as a result of it being a minimally invasive procedure. However, further study with large sample sizes and longer follow-up durations is required to validate the effects of these dynamic stabilizers. PMID- 27185603 TI - Ischemia-modified albumin levels in the prediction of acute critical neurological findings in carbon monoxide poisoning. AB - The aim of the study was to determine whether serum ischemia-modified albumin (IMA) levels in patients with carbon monoxide (CO) poisoning were higher compared with a control group of healthy volunteers. In addition, the study sought to determine if there was a correlation between serum IMA levels and carboxyhemoglobin (COHB) levels and other critical neurological findings (CNFs). In this prospective study, the IMA levels of 100 patients with CO poisoning and 50 control individuals were compared. In addition, the IMA and COHB levels were analyzed according to absence or presence CNFs in patients with CO poisoning. The levels of IMA (mg/dL) on admittance, and during the 1(st) hour and 3(rd) hour, in patients with CO poisoning (49.90 +/- 35.43, 30.21 +/- 14.81, and 21.87 +/- 6.03) were significantly higher, compared with the control individuals (17.30 +/- 2.88). The levels of IMA in the 6(th) hour were not higher compared with control individuals. The levels of IMA on admittance, and during the 1(st) hour, 3(rd) hour, and 6(th) hour, and COHB (%) levels in patients who had CNFs were higher compared with IMA levels and COHB levels in patients who had no CNFs (p < 0.001). However, when the multivariate model was created, it was observed that IMA level on admittance was a poor indicator for prediction of CNFs (odds ratio = 1.05; 95% confidence interval, 1.01-1.08). We therefore concluded that serum IMA levels could be helpful in the diagnosis of CO poisoning. However, we believe that IMA levels cannot be used to predict which patients will develop CNFs due to CO poisoning. PMID- 27185605 TI - Red cell distribution width is associated with albuminuria in adults with familial Mediterranean fever. AB - Systematic inflammation, enhanced oxidative stress, and endothelial dysfunction are important for evolution and progression of renal damage, and they cause an increase in red cell distribution width (RDW). Familial Mediterranean fever (FMF) patients who are in the attack-free period and its relation with albuminuria and performance on assessment of microalbuminuria. One hundred and seventy-seven patients who had been diagnosed in accordance with Tel-hoshmer criteria and were in the attack-free period, and 143 age- and sex-matched healthy individuals were enrolled in our study. RDW values of FMF patients were higher compared with those of the controls (13.85 +/- 1.07 and 13.15 +/- 0.91, respectively; p < 0.0001). RDW values of FMF patients with microalbuminuria were higher compared with those of FMF patients with normoalbuminuria and the control group (p = 0.002 and p < 0.0001, respectively). RDW values of FMF patients with normoalbuminuria were higher compared with those of the control group (p < 0.0001). We have showed RDW levels are positively correlated with albuminuria (r = 0.185, p = 0.014). When assessing microalbuminuria with RDW in the patients, a cutoff value of 13.85 with sensitivity of 60%, specificity of 62%, and p = 0.002 (area under curve: 0.651, 95% confidence interval 0.563-0.738), was observed according to receiver operating characteristic curve analysis. Among the various variables associated with albuminuria in multivariate logistic regression analyses, RDW remained an independent predictor of albuminuria (95% confidence interval 0.479-0.942, p = 0.021). RDW may be associated with albuminuria in FMF patients and it can be a predictor of microalbuminuria. PMID- 27185606 TI - Eosinophilic meningitis caused by Angiostrongylus cantonensis mimicking embolic stroke. PMID- 27185607 TI - Successful diagnosis of intrahepatic splenosis mimicking hepatic tumor. PMID- 27185608 TI - A study of the effectiveness of machine learning methods for classification of clinical interview fragments into a large number of categories. AB - This study examines the effectiveness of state-of-the-art supervised machine learning methods in conjunction with different feature types for the task of automatic annotation of fragments of clinical text based on codebooks with a large number of categories. We used a collection of motivational interview transcripts consisting of 11,353 utterances, which were manually annotated by two human coders as the gold standard, and experimented with state-of-art classifiers, including Naive Bayes, J48 Decision Tree, Support Vector Machine (SVM), Random Forest (RF), AdaBoost, DiscLDA, Conditional Random Fields (CRF) and Convolutional Neural Network (CNN) in conjunction with lexical, contextual (label of the previous utterance) and semantic (distribution of words in the utterance across the Linguistic Inquiry and Word Count dictionaries) features. We found out that, when the number of classes is large, the performance of CNN and CRF is inferior to SVM. When only lexical features were used, interview transcripts were automatically annotated by SVM with the highest classification accuracy among all classifiers of 70.8%, 61% and 53.7% based on the codebooks consisting of 17, 20 and 41 codes, respectively. Using contextual and semantic features, as well as their combination, in addition to lexical ones, improved the accuracy of SVM for annotation of utterances in motivational interview transcripts with a codebook consisting of 17 classes to 71.5%, 74.2%, and 75.1%, respectively. Our results demonstrate the potential of using machine learning methods in conjunction with lexical, semantic and contextual features for automatic annotation of clinical interview transcripts with near-human accuracy. PMID- 27185609 TI - Phenotypes of prediabetes and stratification of cardiometabolic risk. AB - Prediabetes is associated with increased risks of type 2 diabetes, cardiovascular disease, dementia, and cancer, and its prevalence is increasing worldwide. Lifestyle and pharmacological interventions in people with prediabetes can prevent the development of diabetes and possibly cardiovascular disease. However, prediabetes is a highly heterogeneous metabolic state, both with respect to its pathogenesis and prediction of disease. Improved understanding of these features and precise phenotyping of prediabetes could help to improve stratification of disease risk. In this Personal View, we focus on the extreme metabolic phenotypes of metabolically healthy obesity and metabolically unhealthy normal weight, insulin secretion failure, insulin resistance, visceral obesity, and non alcoholic fatty liver disease. We present new analyses aimed at improving characterisation of phenotypes in lean, overweight, and obese people with prediabetes. We discuss evidence from lifestyle intervention studies to explore whether these phenotypes can also be used for individualised prediction and prevention of cardiometabolic diseases. PMID- 27185611 TI - [The French speaking teams must be provided with instruments to help in the diagnosis of autism spectrum disorders in adults with no intellectual disability]. PMID- 27185610 TI - Diagnostic performance of CT and MRI on the detection of symptomatic intracranial dural arteriovenous fistula: a meta-analysis with indirect comparison. AB - INTRODUCTION: This study aims to review the diagnostic performance of computed tomography (CT) and magnetic resonance imaging (MRI) in symptomatic dural arteriovenous fistula (DAVF). METHODS: EMBASE, PubMed, and Cochrane Library were searched until April 2015 for studies which compared CT, MRI, or both with angiography for the detection of DAVF. The diagnostic performances of MRI and CT were indirectly compared using modality as a covariate in the analysis. RESULTS: Thirteen studies met our inclusion criteria. MRI had a sensitivity of 0.90 (95 % confidence interval (CI) = 0.83-0.94) and specificity of 0.94 (95 % CI = 0.90 0.96). CT had a sensitivity of 0.80 (95 % CI = 0.62-0.90) and specificity of 0.87 (95 % CI = 0.74-0.94). MRI showed better diagnostic performance than CT (p = 0.02). Contrast medium use and time-resolved MR angiography did not improve MRI diagnostic performance (p = 0.31 and 0.44, respectively). CONCLUSION: Both CT and MRI had good diagnostic performance. MRI was better than CT on the detection of symptomatic intracranial dural arteriovenous fistula in the indirect comparison. PMID- 27185612 TI - Shape selection in Landsat time series: a tool for monitoring forest dynamics. AB - We present a new methodology for fitting nonparametric shape-restricted regression splines to time series of Landsat imagery for the purpose of modeling, mapping, and monitoring annual forest disturbance dynamics over nearly three decades. For each pixel and spectral band or index of choice in temporal Landsat data, our method delivers a smoothed rendition of the trajectory constrained to behave in an ecologically sensible manner, reflecting one of seven possible 'shapes'. It also provides parameters summarizing the patterns of each change including year of onset, duration, magnitude, and pre- and postchange rates of growth or recovery. Through a case study featuring fire, harvest, and bark beetle outbreak, we illustrate how resultant fitted values and parameters can be fed into empirical models to map disturbance causal agent and tree canopy cover changes coincident with disturbance events through time. We provide our code in the r package ShapeSelectForest on the Comprehensive R Archival Network and describe our computational approaches for running the method over large geographic areas. We also discuss how this methodology is currently being used for forest disturbance and attribute mapping across the conterminous United States. PMID- 27185613 TI - Tubular Constructs as Artificial Urinary Conduits. AB - PURPOSE: A readily available artificial urinary conduit might be substituted for autologous bowel in standard urinary diversions and minimize bowel associated complications. However, the use of large constructs remains challenging as host cellular ingrowth and/or vascularization is limited. We investigated large, reinforced, collagen based tubular constructs in a urinary diversion porcine model and compared subcutaneously pre-implanted constructs to cell seeded and basic constructs. MATERIALS AND METHODS: Reinforced tubular constructs were prepared from type I collagen and biodegradable Vicryl(r) meshes through standard freezing, lyophilization and cross-linking techniques. Artificial urinary conduits were created in 17 female Landrace pigs, including 7 with a basic untreated construct, 5 with a construct seeded with autologous urothelial and smooth muscle cells, and 5 with a free graft formed by subcutaneous pre implantation of a basic construct. All pigs were evaluated after 1 month. RESULTS: The survival rate was 94%. At evaluation 1 basic and 1 cell seeded conduit were occluded. Urinary flow was maintained in all conduits created with pre-implanted constructs. Pre-implantation of the basic construct resulted in a vascularized tissue tube, which could be used as a free graft to create an artificial conduit. The outcome was favorable compared to that of the other conduits. Urinary drainage was better, hydroureteronephrosis was limited and tissue regeneration was improved. CONCLUSIONS: Subcutaneous pre-implantation of a basic reinforced tubular construct resulted in a vascularized autologous tube, which may potentially replace bowel in standard urinary diversions. To our knowledge we introduce a straightforward 2-step procedure to create artificial urinary conduits in a large animal model. PMID- 27185614 TI - Referral Criteria for Outpatient Palliative Cancer Care: A Systematic Review. AB - BACKGROUND: Outpatient palliative care clinics facilitate early referral and are associated with improved outcomes in cancer patients. However, appropriate candidates for outpatient palliative care referral and optimal timing remain unclear. We conducted a systematic review of the literature to identify criteria that are considered when an outpatient palliative cancer care referral is initiated. METHODS: We searched Ovid MEDLINE (1948-2013 citations) and Ovid Embase (1947-2015 citations) for articles related to outpatient palliative cancer care. Two researchers independently reviewed each citation for inclusion and extracted the referral criteria. The interrater agreement was high (kappa = 0.96). RESULTS: Of the 186 publications in our initial search, 21 were included in the final sample. We identified 20 unique referral criteria. Among these, 6 were recurrent themes, which included physical symptoms (n = 13 [62%]), cancer trajectory (n = 13 [62%]), prognosis (n = 7 [33%]), performance status (n = 7 [33%]), psychosocial distress (n = 6 [29%]), and end-of-life care planning (n = 5 [24%]). We found significant variations among the articles regarding the definition of advanced cancer and the assessment tools for symptom/distress screening. The Edmonton Symptom Assessment Scale (n = 7 [33%]) and the distress thermometer (n = 2 [10%]) were used most often. Furthermore, there was a lack of consensus in the cutoffs in symptom assessment tools and timing for outpatient palliative care referral. CONCLUSION: This systematic review identified 20 criteria including 6 recurrent themes for outpatient cancer palliative care referral. It highlights the significant heterogeneity regarding the timing and process for referral and the need for further research to develop standardized referral criteria. IMPLICATIONS FOR PRACTICE: Outpatient palliative care clinics improve patient outcomes; however, it remains unclear who is appropriate for referral and what is the optimal timing. A better understanding of the referral criteria would help (a) referring clinicians to identify appropriate patients for palliative care interventions, (b) administrators to assess their programs with set benchmarks for quality improvement, (c) researchers to standardize inclusion criteria, and (d) policymakers to develop clinical care pathways and allocate appropriate resources. This systematic review identified 20 criteria including 6 recurrent themes for outpatient palliative cancer care referral. It represents the first step toward developing standardized referral criteria. PMID- 27185617 TI - Corrigendum to "Missed or Delayed Cervical Spine or Spinal Cord Injuries Treated at a Tertiary Referral Hospital in Rwanda" [World Neurosurg. 87 (2016) 269-276]. PMID- 27185615 TI - Sorafenib Effectiveness in Advanced Hepatocellular Carcinoma. AB - BACKGROUND: Phase III trials show sorafenib improves survival in advanced hepatocellular carcinoma (HCC). Because of narrow trial eligibility, results may not be generalizable to a broader HCC population. We sought to evaluate the effectiveness of initial sorafenib versus no treatment among Medicare beneficiaries with advanced HCC. MATERIALS AND METHODS: Patients with advanced HCC diagnosed from 2008 to 2011 were identified from the Surveillance, Epidemiology, and End Results-Medicare database. Eligible patients received initial sorafenib or no therapy and were covered by Medicare parts A, B, and D. Sorafenib use and outcomes were described in this population. Using a propensity score (PS)-matched sample, we compared the effectiveness of sorafenib versus no treatment by Cox proportional hazards and binomial regression, using a landmark requiring all patients to survive >=60 days after diagnosis. RESULTS: Of 1,532 patients, 27% received initial sorafenib. Median duration of sorafenib use was 60 days (interquartile range [IQR], 30-107 days), and median survival from first prescription was 3 months (IQR, 1-8 months). In the PS-matched cohort, median survival was 3 months from the 60-day landmark in sorafenib-treated (n = 223) and 2 months in untreated (n = 223) patients (adjusted hazard ratio, 0.95 [95% confidence interval (CI), 0.78-1.16]). Sorafenib was associated with a nonsignificant reduction in mortality at 3 months (44% versus 51%; adjusted risk ratio, 0.88 [95% CI, 0.72-1.07]), but no reduction thereafter. CONCLUSION: Survival after sorafenib initiation in newly diagnosed Medicare beneficiaries with HCC is exceptionally short, suggesting trial results are not generalizable to all HCC patients. The downsides of sorafenib use-high drug-related symptom burden and high drug cost-must be considered in light of this minimal benefit. IMPLICATIONS FOR PRACTICE: The findings of a median survival of only 3 months in Medicare beneficiaries with HCC prescribed sorafenib as first-line therapy highlight the questionable value of sorafenib in this population. Patients should be cautioned that outside of the narrow confines of randomized trials, their life expectancy may be very short, and any benefit of sorafenib is likely to be quite small. Given that sorafenib causes considerable adverse effects and offers no symptom palliation, supportive care should be discussed as a reasonable alternative to sorafenib, particularly for patients who have a poor performance status or advanced cirrhosis. PMID- 27185616 TI - Gender differences in CNV burden do not confound schizophrenia CNV associations. AB - Compared with the general population, an excess of rare copy number variants (CNVs) has been identified in people with schizophrenia. Females with neurodevelopmental disorders and in the general population have been reported to carry more large, rare CNVs than males. Given that many schizophrenia datasets do not have equal gender ratios in cases and controls, sex differences in CNV burden might have impacted on estimates of case-related CNV burden and also on associations to individual loci. In a sample of 13,276 cases and 17,863 controls, we observed a small but significant excess of large (>=500 Kb), rare (<1%) CNVs in females compared with males in both cases and controls (OR = 1.17, P = 0.0012 for controls; OR = 1.11, P = 0.045 for cases). The burden of 11 schizophrenia associated CNVs was significantly higher in female cases compared with male cases (OR = 1.38, P = 0.0055), but after accounting for the rates of CNVs in controls, we found no significant gender difference in the risk conferred by these loci. Controlling for gender had a negligible effect on the significance of association between specific CNVs and schizophrenia. The female excess of large CNVs in both cases and controls suggests a female protective mechanism exists for deleterious CNVs that may extend beyond neurodevelopmental phenotypes. PMID- 27185618 TI - Nobuo Murakami, executive chef of the Imperial Hotel and Ambroise Pare, surgeon in ordinary to the kings of France. PMID- 27185619 TI - Congenital cardiac rhabdomyoma. PMID- 27185620 TI - Developmental Hazards Among Young Alcohol Intoxicated Patients. AB - PURPOSE: The rising numbers of alcohol intoxicated adolescents (AIA) treated in emergency care units in several European countries have drawn attention to this target group for prevention. To our knowledge, this is the first study to assess a broad array of developmental hazards and their stability in AIA and to compare their distribution with representative samples (RS). METHODS: A multisite cohort study of AIA aged 13-17 years assessed, in the hospital (t0) and 6 months later (t1), (family) violence, cannabis and alcohol use, school problems, delinquency, homelessness, depression, and suicidality, using items from representative German surveys: Children and Adolescent Health Survey (KiGGS), Childhood Trauma Questionnaire and Communities That Care Youth Survey. We calculated the differences between AIA and RS and corresponding 95% confidence intervals. For AIA respondents who completed t0 and t1 information, we calculated prevalence/persistence/incidence of developmental hazards and corresponding 95% confidence interval. RESULTS: A total of 342 AIA participated at t0, 228 at t1 (67%). AIA had a significantly higher burden of concomitant risks regarding physical and emotional family abuse, (sexual) victimization, cannabis use, binge drinking, school expulsion, police arrest, gang membership, and being violent. Six months after hospitalization, emotional family abuse (34.1%), cannabis use (23.5%), depression (14.8%), and being violent (13.2%) were especially prevalent. CONCLUSIONS: Developmental hazards are up to six times more prevalent in AIA than in RS. Therefore, when assessing the risk profile of AIA, it is important to consider developmental hazards as well as detrimental alcohol use. PMID- 27185621 TI - Ethical Considerations in Recruiting Online and Implementing a Text Messaging Based HIV Prevention Program With Gay, Bisexual, and Queer Adolescent Males. AB - PURPOSE: There is a dearth of HIV prevention/healthy sexuality programs developed for adolescent gay and bisexual males (AGBM) as young as 14 years old, in part because of the myriad ethical concerns. To address this gap, we present our ethics-related experiences implementing Guy2Guy, a text messaging-based HIV prevention/healthy sexuality program, in a randomized controlled trial of 302 14- to 18-year-old sexual minority males. METHODS: Potential risks and efforts to reduce these risks are discussed within the framework of the Belmont Report: Respect for persons, beneficence (e.g., risks and benefits), and justice (e.g., fair distribution of benefits and burdens). RESULTS: To ensure "respect for persons," online enrollment was coupled with telephone assent, which included assessing decisional capacity to assent. Beneficence was promoted by obtaining a waiver of parental permission and using a self-safety assessment to help youth evaluate their risk in taking part. Justice was supported through efforts to develop and test the program among those who would be most likely to use it if it were publicly available (e.g., youth who own a cell phone and are enrolled in an unlimited text messaging plan), along with the use of recruitment targets to ensure a racially, ethnically, and regionally diverse sample. CONCLUSIONS: It is possible to safely implement a sensitive and HIV prevention/healthy sexuality program with sexual minority youth as young as 14 years old when a rigorous ethical protocol is in place. PMID- 27185622 TI - Harsh Parenting and Food Insecurity in Adolescence: The Association With Emerging Adult Obesity. AB - PURPOSE: As the first study of its kind, the overall purpose of this article was to examine the relationships and interactions between harsh parenting (HP) and food insecurity (FI) in adolescence on the development of overweight/obesity (OW/OB) in emerging adulthood. METHODS: Data came from the Iowa Youth and Families Project, a longitudinal study of 451 adolescent youth and their families that began in 1989 in the rural Midwest. Adolescents were aged 13 years at the initial assessment, and weight status in emerging adulthood was measured 10 years later at age 23. RESULTS: Experiencing HP in adolescence predicted greater odds of OW/OB at 23 years old. Higher body mass indexes of the adolescent and his or her father in adolescence also increased the odds of being OW/OB at 23 years. Having parents with higher levels of education lowered the odds of being OW/OB in emerging adulthood. Finally, females who experienced high levels of FI and HP in adolescence had higher odds of OW/OB at 23 years in comparison to males. CONCLUSIONS: HP, in combination with FI in adolescence, predicted OW/OB for females in emerging adulthood but not for males. This study contributes to an understanding of the interplay between multiple influences in adolescence: namely, parenting and economic influences. Assessing antecedents to OW/OB in emerging adulthood via multiple pathways provides a more complex understanding of how and why adolescents turn into OW/OB adults. PMID- 27185624 TI - The E119D neuraminidase mutation identified in a multidrug-resistant influenza A(H1N1)pdm09 isolate severely alters viral fitness in vitro and in animal models. AB - We recently isolated an influenza A(H1N1)pdm09 E119D/H275Y neuraminidase (NA) variant from an immunocompromised patient who received oseltamivir and zanamivir therapies. This variant demonstrated cross resistance to zanamivir, oseltamivir, peramivir and laninamivir. In this study, the viral fitness of the recombinant wild-type (WT), E119D and E119D/H275Y A(H1N1)pdm09 viruses was evaluated in vitro and in experimentally-infected C57BL/6 mice and guinea pigs. In replication kinetics experiments, viral titers obtained with the E119D and E119D/H275Y recombinants were up to 2- and 4-log lower compared to the WT virus in MDCK and ST6GalI-MDCK cells, respectively. Enzymatic studies revealed that the E119D mutation significantly decreased the surface NA activity. In experimentally infected mice, a 50% mortality rate was recorded in the group infected with the WT recombinant virus whereas no mortality was observed in the E119D and E119D/H275Y groups. Mean lung viral titers on day 5 post-inoculation for the WT (1.2 +/- 0.57 * 10(8) PFU/ml) were significantly higher than those of the E119D (9.75 +/- 0.41 * 10(5) PFU/ml, P < 0.01) and the E119D/H275Y (1.47 +/- 0.61 * 10(6) PFU/ml, P < 0.01) groups. In guinea pigs, comparable seroconversion rates and viral titers in nasal washes (NW) were obtained for the WT and mutant index and contact groups. However, the D119E reversion was observed in most NW samples of the E119D and E119D/H275Y animals. In conclusion, the E119D NA mutation that could emerge in A(H1N1)pdm09 viruses during zanamivir therapy has a significant impact on viral fitness and such mutant is unlikely to be highly transmissible. PMID- 27185625 TI - RSV neutralization by palivizumab, but not by monoclonal antibodies targeting other epitopes, is augmented by Fc gamma receptors. AB - Palivizumab efficiently blocks respiratory syncytial virus (RSV) infection in vitro. However, virus neutralization assays generally omit Fc region-mediated effects. We investigated the neutralization activity of RSV-specific monoclonal antibodies on cells with Fc receptors. Subneutralizing concentrations of antibodies resulted in antibody-dependent enhancement of RSV infection in monocytic cells. Contrary to antibodies targeting other epitopes, the neutralization by palivizumab was augmented in cells with Fc receptors. This unrecognized characteristic of palivizumab may be relevant for its performance in vivo. PMID- 27185623 TI - Establishment of an inducible HBV stable cell line that expresses cccDNA dependent epitope-tagged HBeAg for screening of cccDNA modulators. AB - Hepatitis B virus (HBV) covalently closed circular (ccc) DNA is essential to the virus life cycle, its elimination during chronic infection is considered critical to a durable therapy but has not been achieved by current antivirals. Despite being essential, cccDNA has not been the major target of high throughput screening (HTS), largely because of the limitations of current HBV tissue culture systems, including the impracticality of detecting cccDNA itself. In response to this need, we have previously developed a proof-of-concept HepDE19 cell line in which the production of wildtype e antigen (HBeAg) is dependent upon cccDNA. However, the existing assay system is not ideal for HTS because the HBeAg ELISA cross reacts with a viral HBeAg homologue, which is the core antigen (HBcAg) expressed largely in a cccDNA-independent fashion in HepDE19 cells. To further improve the assay specificity, we report herein a "second-generation" cccDNA reporter cell line, termed HepBHAe82. In the similar principle of HepDE19 line, an in-frame HA epitope tag was introduced into the precore domain of HBeAg open reading frame in the transgene of HepBHAe82 cells without disrupting any cis element critical for HBV replication and HBeAg secretion. A chemiluminescence ELISA assay (CLIA) for the detection of HA-tagged HBeAg with HA antibody serving as capture antibody and HBeAb serving as detection antibody has been developed to eliminate the confounding signal from HBcAg. The miniaturized HepBHAe82 cell based assay system exhibits high level of cccDNA-dependent HA-HBeAg production and high specific readout signals with low background. We have also established a HepHA-HBe4 cell line expressing transgene-dependent HA-HBeAg as a counter screen to identify HBeAg inhibitors. The HepBHAe82 system is amenable to antiviral HTS development, and can be used to identify host factors that regulate cccDNA metabolism and transcription. PMID- 27185626 TI - Luteolin inhibits Epstein-Barr virus lytic reactivation by repressing the promoter activities of immediate-early genes. AB - The lytic reactivation of Epstein-Barr virus (EBV) has been reported to be strongly associated with several human diseases, including nasopharyngeal carcinoma (NPC). Inhibition of the EBV lytic cycle has been shown to be of great benefit in the treatment of EBV-associated diseases. The administration of dietary compounds is safer and more convenient than other approaches to preventing EBV reactivation. We screened several dietary compounds for their ability to inhibit EBV reactivation in NPC cells. Among them, the flavonoid luteolin showed significant inhibition of EBV reactivation. Luteolin inhibited protein expression from EBV lytic genes in EBV-positive epithelial and B cell lines. It also reduced the numbers of EBV-reactivating cells detected by immunofluorescence analysis and reduced the production of virion. Furthermore, luteolin reduced the activities of the promoters of the immediate-early genes Zta (Zp) and Rta (Rp) and also inhibited Sp1-luc activity, suggesting that disruption of Sp1 binding is involved in the inhibitory mechanism. CHIP analysis revealed that luteolin suppressed the activities of Zp and Rp by deregulating Sp1 binding. Taken together, luteolin inhibits EBV reactivation by repressing the promoter activities of Zp and Rp, suggesting luteolin is a potential dietary compound for prevention of virus infection. PMID- 27185627 TI - Comparative Evaluation of the Artefacts Index of Dental Materials on Two Dimensional Cone-beam Computed Tomography. AB - The aim of the study was to propose the artefact index on cone-beam computed tomography (CBCT) images of clinical prosthodontics materials, and to compare the effect of the artefacts on CBCT image clarity of normal oral tissues. Seven spheres of different materials were secured on the centre of a resin baseboard, respectively, and four human molars in vitro were placed at 10 mm front, back, left and right of the sphere. The board was scanned using CBCT with the same setting. 10 tomographic images from each of the seven data sets with clear artefacts was selected. The grayscale measuring tool of Photoshop software was used to measure the grayscale (G0) within the boundary of tomographic image and the grayscales of the streaky artefacts that were 1 mm and 20 mm outside the circular boundary (G1 and G2). The arc length, L1, of the circular boundary with artefacts was measured; the circumference, L2, was calculated. The artefact index, A, was determined as (G1/G0) * 0.5 + (G2/G1) * 0.4 + (L2/L1) * 0.1. The artefact index A can comprehensively represent the effect of artefacts on CBCT image clarity for oral tissue. PMID- 27185628 TI - Toxic Megacolon: A Review for Emergency Department Clinicians. PMID- 27185629 TI - Synergetic enhancement of gold nanoparticles and 2-mercaptobenzothiazole as highly-sensitive sensing strategy for tetrabromobisphenol A. AB - Various gold nanoparticles (AuNPs) were in-situ prepared on the electrode surface through electrochemical reduction under different potentials such as -0.60, 0.50, -0.40, -0.30 and -0.20 V. The reduction potentials heavily affect the surface morphology and electrochemical activity of AuNPs such as effective area and catalytic ability, as confirmed using atomic force microscopy and electrochemical impedance spectroscopy. The electrochemical behaviors of tetrabromobisphenol A (TBBPA), a widely-existed pollutant with severe adverse health effects, were studied. The oxidation activity of TBBPA enhances obviously on the surface of AuNPs, and the signal improvements of TBBPA show difference on the prepared AuNPs. Interestingly, the existence of 2-mercaptobenzothiazole (MBT) further improves the oxidation signals of TBBPA on AuNPs. The synergetic enhancement effects of AuNPs and MBT were studied using cyclic voltammetry and chronocoulometry. The numerous nano-scaled gold particles together with the strong hydrophobic interaction between TBBPA and the assembled MBT on AuNPs jointly provide highly-effective accumulation for TBBPA. As a result, a sensitive and simple electrochemical method was developed for the direct determination of TBBPA, with detection limit of 0.12 MUg L(-1) (0.22 nM). The practical applications in water samples manifest that this new sensing system is accurate and feasible. PMID- 27185630 TI - Distribution analysis of profilin isoforms at transcript resolution with mRNA-seq and secondary structure in various organs of Rattus norvegicus. AB - Profilin (Pfn) is an actin binding protein, ubiquitously found in mammals and is essential for the actin polymerization in cells. In brain, it plays a pivotal role in neurogenesis and synapse formation by interacting with various proteins. Four Pfn isoforms have been identified in mammals. This study presents the identification and transcriptional expression of various Pfn isoforms (Pfn1, Pfn2, Pfn3 and Pfn4) in brain, heart, kidney, liver, and muscle and testis of Rattus norvegicus. Organs have been classified into groups based on some similarities. Group I includes brain and testis, Group II includes skeletal muscle and heart, while Group III includes kidney and liver. Pfn1 has been identified in all groups, Pfn2 and Pfn3 have been identified in group I, group III and in one organ (skeletal muscle) of group II. To the best of the authors knowledge, no report of Pfn1 and Pfn2 presence in testis, Pfn3 in brain, liver and skeletal muscle, Pfn4 in kidney and skeletal muscle exists to date. Transcriptional expression showed variations among expression level of different Pfn isoforms in various organs with respect to the control gene GADPH. We hypothesize that this could be attributed to profilin isoform specific mRNA structure and corresponding motifs, which generally contribute to similar or varied decay rates, cellular localization, post transcriptional regulation pattern and ligand binding. PMID- 27185631 TI - Endoplasmic reticulum stress mediates JNK-dependent IRS-1 serine phosphorylation and results in Tau hyperphosphorylation in amyloid beta oligomer-treated PC12 cells and primary neurons. AB - AIMS: Endoplasmic reticulum stress (ERS) and insulin signaling impairment are commonly observed in Alzheimer's disease (AD), but the association between these two factors in AD has not been carefully studied. In peripheral insulin signaling impairment, ERS interferes with insulin signaling through c-Jun. N-terminal kinase (JNK)-dependent insulin receptor substance-1 (IRS-1) serine phosphorylation. We conducted this study to determine whether a similar mechanism contributes to insulin signaling impairment in AD pathogenesis. METHODS: Changes in the levels of ERS markers, JNK activation, the insulin signaling status and Tau hyperphosphorylation were examined in amyloid beta1-42 (Abeta1-42) oligomer treated PC12 cells and primary neurons by western blotting and real-time fluorescence quantitative PCR. Inhibitors of ERS and JNK were utilized to confirm their association. RESULTS: Our results demonstrated that Abeta1-42 oligomers significantly induced ERS and JNK activation. In addition, in response to Abeta1 42 oligomers, IRS-1 phosphorylation at serines 307, 318 and 612 was increased. Further, an increase in Tau hyperphosphorylation at threonine 181 was observed following Abeta1-42 oligomer treatment. Moreover, inhibition of ERS or JNK could partially reverse the changes induced by the Abeta1-42 oligomers. CONCLUSIONS: These findings suggest that ERS may contribute to insulin signaling impairment in AD through JNK-dependent IRS-1 serine phosphorylation. The ERS/JNK/IRS-1 pathway may be involved in Abeta1-42 oligomer-induced Tau hyperphosphorylation in AD. PMID- 27185632 TI - Functional redundancy in phenol and toluene degradation in Pseudomonas stutzeri strains isolated from the Baltic Sea. AB - In the present study we describe functional redundancy of bacterial multicomponent monooxygenases (toluene monooxygenase (TMO) and toluene/xylene monooxygenase (XylAM) of TOL pathway) and cooperative genetic regulation at the expression of the respective catabolic operons by touR and xylR encoded regulatory circuits in five phenol- and toluene-degrading Pseudomonas stutzeri strains. In these strains both toluene degradation pathways (TMO and Xyl) are active and induced by toluene and phenol. The whole genome sequence of the representative strain 2A20 revealed the presence of complete TMO- and Xyl-upper pathway operons together with two sets of lower catechol meta pathway operons, as well as phenol-degrading operon in a single 292,430bp contig. The much lower GC content and analysis of the predicted ORFs refer to the plasmid origin of the approximately 130kb region of this contig, containing the xyl, phe and tou genes. The deduced amino acid sequences of the TMO, XylA and the large subunit of phenol monooxygenase (LmPH) show 98-100% identity with the respective gene products of the strain Pseudomonas sp. OX1. In both strains 2A20 and OX1 the meta-cleavage pathways for catechol degradation are coded by two redundant operons (phe and xyl). We show that in the strain 2A20 TouR and XylR are activated by different effector molecules, phenol and toluene, respectively, and they both control transcription of the xyl upper, tou (TMO) and phe catabolic operons. Although the growth parameters of redundant strains did not show advantage at toluene biodegradation, the functional redundancy could provide better flexibility to the bacteria in environmental conditions. PMID- 27185633 TI - A three-step programmed method for the identification of causative gene mutations of maturity onset diabetes of the young (MODY). AB - To establish a three-step programmed method to find gene mutations related to maturity onset diabetes of the young (MODY). Target region capture and next generation sequencing (NGS) were performed using customized oligonucleotide probes designed to capture suspected genes for MODY in 11 probands with clinically diagnosed MODY. The suspected associations of certain genes with MODY were then confirmed by Sanger sequencing in the probands and their family members. Finally, to validate variants of one of the genes of interest (glucokinase, GCK) as pathogenic mutations, protein function editing by the variant genes was assessed. In the target region capture and NGS phase, a total of nine variants of seven genes (GCK, WFS1, SLC19A2, SH2B1, SERPINB4, RFX6, and GATA6) were identified in eight probands. Two heterozygous GCK mutations located on the same allele (p.Leu77Arg and p.Val101Met) were identified in a MODY family. Sanger sequencing was used to confirm the variants identified by NGS to be present in probands and their diabetic family members, but not in non-diabetic family members. Finally, enzyme kinetic and thermal stability analyses revealed that the p.Leu77Arg mutation or the p.Leu77Arg mutation in combination with the p.Val101Met mutation inactivates GCK function and stability, while mutation of p.Val101Met alone does not. The p.Leu77Arg but not p.Val101Met GCK mutation is therefore considered a pathogenic mutation associated with MODY. Genetic screening coupled with gene-editing protein function testing is an effective and reliable method by which causative gene mutations of MODY can be identified. PMID- 27185634 TI - De novo assembly and transcriptome analysis of sclerotial development in Wolfiporia cocos. AB - Wolfiporia cocos Ryvarden et Gilbertson, a well-known medicinal fungus in the Basidiomycetes, is widely distributed in East Asia. Its dried sclerotium, which is known as Fuling in China, has been used as a traditional crude drug in Chinese traditional medicine for thousand years. However, little is known about how the sclerotium is developed at the genetic level. In this study, the de novo sequencing of sclerotia of W. cocos (S1_initial stage; S2_developmental stage and S3_mature stage) was carried out by illumina HiSeq 2000 technology. 27,438 unigenes were assembled from ~30Gbp raw data, and 12,093 unigenes were significantly annotated. The analysis of expression profiles during development returned 304 differentially expressed genes (DEGs), which were clustered into four different groups according to their expression trends. Especially for the maturation stage (S3), the sclerotium exhibited a markedly different expression profile from other stages. We further showed that peroxisome, unsaturation of fatty acids and degradation pathway were respectively prevalent in S1, S2 and S3 stages as evidenced by enrichment analysis. To our knowledge, this study represents the first report of sclerotial development transcriptomics in W. cocos. The obtained results provide novel insights into the developmental biology of the sclerotia, which is helpful for future studies about cultivation and breeding of W. cocos. PMID- 27185636 TI - Scalable anti-Markovnikov hydrobromination of aliphatic and aromatic olefins. AB - To improve access to a key synthetic intermediate we targeted a direct hydrobromination-Negishi route. Unsurprisingly, the anti-Markovnikov addition of HBr to estragole in the presence of AIBN proved successful. However, even in the absence of an added initiator, anti-Markovnikov addition was observed. Re examination of early reports revealed that selective Markovnikov addition, often simply termed "normal" addition, is not always observed with HBr unless air is excluded, leading to the rediscovery of a reproducible and scalable initiator free protocol. PMID- 27185635 TI - Interface Engineering of Organic Schottky Barrier Solar Cells and Its Application in Enhancing Performances of Planar Heterojunction Solar Cells. AB - In this work, we describe the performance of organic Schottky barrier solar cells with the structure of ITO/molybdenum oxide (MoOx)/boron subphthalocyanine chloride (SubPc)/bathophenanthroline (BPhen)/Al. The SubPc-based Schottky barrier solar cells exhibited a short-circuit current density (Jsc) of 2.59 mA/cm(2), an open-circuit voltage (Voc) of 1.06 V, and a power conversion efficiency (PCE) of 0.82% under simulated AM1.5 G solar illumination at 100 mW/cm(2). Device performance was substantially enhanced by simply inserting thin organic hole transport material into the interface of MoOx and SubPc. The optimized devices realized a 180% increase in PCE of 2.30% and a peak Voc as high as 1.45 V was observed. We found that the improvement is due to the exciton and electron blocking effect of the interlayer and its thickness plays a vital role in balancing charge separation and suppressing quenching effect. Moreover, applying such interface engineering into MoOx/SubPc/C60 based planar heterojunction cells substantially enhanced the PCE of the device by 44%, from 3.48% to 5.03%. Finally, we also investigated the requirements of the interface material for Schottky barrier modification. PMID- 27185637 TI - Component of Caramel Food Coloring, THI, Causes Lymphopenia Indirectly via a Key Metabolic Intermediate. AB - Caramel color is widely used in the food industry, and its many variations are generally considered to be safe. It has been known for a long time that THI (2 acetyl-4-(tetrahydroxybutyl)imidazole), a component of caramel color III, causes lymphopenia in animals through sphingosine 1-phosphate (S1P) lyase (S1PL) inhibition. However, this mechanism of action has not been fully validated because THI does not inhibit S1PL in vitro. To reconcile this situation, we examined molecular details of THI mechanism of action using "smaller" THI derivatives. We identified a bioactive derivative, A6770, which has the same lymphopenic effect as THI via S1PL inhibition. In the case of A6770 we observe this effect both in vitro and in vivo, and demonstrate that A6770 is phosphorylated and inhibits S1PL in the same way as 4-deoxypyridoxine. In addition, A6770 was detected in rat plasma following oral administration of THI, suggesting that A6770 is a key metabolic intermediate of THI. PMID- 27185638 TI - GSTP1 Is a Driver of Triple-Negative Breast Cancer Cell Metabolism and Pathogenicity. AB - Breast cancers possess fundamentally altered metabolism that fuels their pathogenicity. While many metabolic drivers of breast cancers have been identified, the metabolic pathways that mediate breast cancer malignancy and poor prognosis are less well understood. Here, we used a reactivity-based chemoproteomic platform to profile metabolic enzymes that are enriched in breast cancer cell types linked to poor prognosis, including triple-negative breast cancer (TNBC) cells and breast cancer cells that have undergone an epithelial mesenchymal transition-like state of heightened malignancy. We identified glutathione S-transferase Pi 1 (GSTP1) as a novel TNBC target that controls cancer pathogenicity by regulating glycolytic and lipid metabolism, energetics, and oncogenic signaling pathways through a protein interaction that activates glyceraldehyde-3-phosphate dehydrogenase activity. We show that genetic or pharmacological inactivation of GSTP1 impairs cell survival and tumorigenesis in TNBC cells. We put forth GSTP1 inhibitors as a novel therapeutic strategy for combatting TNBCs through impairing key cancer metabolism and signaling pathways. PMID- 27185639 TI - Discovery of Phosphorylated Peripherin as a Major Humoral Autoantigen in Type 1 Diabetes Mellitus. AB - A major goal in understanding autoimmune diseases is to define the antigens that elicit a self-destructive immune response, but this is a difficult endeavor. In an effort to discover autoantigens associated with type 1 diabetes (T1D), we used epitope surrogate technology that screens combinatorial libraries of synthetic molecules for compounds that could recognize disease-linked autoantibodies and enrich them from serum. Autoantibodies from one patient revealed a highly phosphorylated form of peripherin, a neuroendocrine filament protein, as a candidate T1D antigen. Peripherin antibodies were detected in 72% of donor patient sera. Further analysis revealed that the T1D-associated antibodies only recognized a dimeric conformation of peripherin. These data explain why peripherin was dismissed as an important T1D antigen previously. The discovery of this novel autoantigen would not have been possible using standard methods, such as hybridizing serum antibodies to recombinant protein arrays, highlighting the power of epitope surrogate technology for probing the mechanism of autoimmune diseases. PMID- 27185640 TI - Intraductal tubular neoplasms of the pancreas: an overview. AB - Intraductal lesions of the pancreas are an uncommon but increasingly recognized group of entities mainly because of advances in imaging technology. In the past, precise categorization and understanding of true pancreatic intraduct neoplasms were hampered not only by their relative rarity but also because of the plethora of terminology and criteria used in nomenclature and diagnosis. Although significant progress has been made in the characterization of some of these lesions, as exemplified by intraductal papillary mucinous neoplasms, understanding of the rare intraductal tubular adenoma (ITA) and intraduct tubular carcinoma (ITC) continues to evolve. By definition, these are a group of intraductal, radiologically detectable neoplasms that can progress to or be associated with invasive adenocarcinoma and, as such, are precursor lesions to pancreatic ductal adenocarcinoma. Their often shared clinical and radiological features make precise histological diagnosis essential for appropriate management and optimal outcome. We provide an overview of these neoplasms and highlight recent developments in the understanding of ITA and ITC which have led to ITA being considered a variant of gastric-type intraductal papillary mucinous neoplasms and ITC being encompassed within the intraductal tubulopapillary neoplasm category. We also emphasize the distinguishing histological features to aid diagnosis of these rare lesions. PMID- 27185641 TI - Analysis of prognosis in CLL: collaboration makes the difference. PMID- 27185642 TI - An international prognostic index for patients with chronic lymphocytic leukaemia (CLL-IPI): a meta-analysis of individual patient data. AB - BACKGROUND: The management of patients with chronic lymphocytic leukaemia is currently undergoing improvements due to novel therapies and a plethora of biological and genetic variables that add prognostic information to the classic clinical staging systems. We established an international consortium with the aim to create an international prognostic index for chronic lymphocytic leukaemia (CLL-IPI) that integrates the major prognostic parameters. METHODS: We used results from a systematic search of the Cochrane Haematological Malignancies Group of MEDLINE, Embase, and Central databases for prospective, clinical phase 2 and 3 trials of chronic lymphocytic leukaemia, published between Jan 1, 1950, and Dec 31, 2010, which identified 13 trials. We contacted the principal investigators of these 13 trials, of which eight agreed to include individual patient data. We used the individual patient data from these phase 3 trials from France, Germany, Poland, the UK, and the USA to create the full analysis dataset. The full analysis dataset was randomly divided, using a random sample procedure, into training and internal-validation datasets. We did a univariate analysis and multivariate analyses using 27 baseline factors and overall survival as an endpoint. We assigned weighted risk scores to each factor included in the final multivariable model. We assessed the discriminatory value using C-statistics and also the validity and reproducibility of the CLL-IPI by subgroup analysis. We used two additional datasets from the Mayo Clinic (Rochester, MN, USA; MAYO cohort) and the SCALE Scandinavian population-based case-control study (SCAN cohort) as the external-validation datasets. FINDINGS: 3472 treatment-naive patients were included in the full analysis dataset; 2308 were randomly segregated into the training dataset and 1164 into the internal-validation dataset. 838 patients were included in the MAYO cohort and 416 in the SCAN cohort. Median age of patients in the full analysis dataset was 61 years (range 27-86). Five independent prognostic factors were identified in the training dataset: TP53 status (no abnormalities vs del[17p] or TP53 mutation or both), IGHV mutational status (mutated vs unmutated), serum beta2-microglobulin concentration (<=3.5 mg/L vs >3.5 mg/L), clinical stage (Binet A or Rai 0 vs Binet B-C or Rai I-IV), and age (<=65 years vs >65 years). Using a weighted grading of the independent factors, a prognostic index was derived that identified four risk groups within the training dataset with significantly different overall survival at 5 years: low (93.2% [95% CI 90.5-96.0]), intermediate (79.3% [75.5-83.2]), high (63.3% [57.9-68.8]), and very high risk (23.3% [12.5-34.1]; log-rank test comparing survival across the four risk groups p<0.0001; C-statistic, c=0.723 [95% CI 0.684-0.752]). These risk groups were confirmed in the internal-validation and external-validation datasets. INTERPRETATION: The CLL-IPI combines genetic, biochemical, and clinical parameters into a prognostic model, discriminating four prognostic subgroups. The CLL-IPI will allow a more targeted management of patients with chronic lymphocytic leukaemia in clinical practice and in trials testing novel drugs. FUNDING: Jose Carreras Leukaemia Foundation. PMID- 27185643 TI - Potential Pitfalls in Estimating Viral Load Heritability. AB - In HIV patients, the set-point viral load (SPVL) is the most widely used predictor of disease severity. Yet SPVL varies over several orders of magnitude between patients. The heritability of SPVL quantifies how much of the variation in SPVL is due to transmissible viral genetics. There is currently no clear consensus on the value of SPVL heritability, as multiple studies have reported apparently discrepant estimates. Here we illustrate that the discrepancies in estimates are most likely due to differences in the estimation methods, rather than the study populations. Importantly, phylogenetic estimates run the risk of being strongly confounded by unrealistic model assumptions. Care must be taken when interpreting and comparing the different estimates to each other. PMID- 27185644 TI - Performance of the HSV OligoGen kit for the diagnosis of herpes simplex virus type 1 and 2. AB - PCR methods are nowadays between the most rapid and sensitive methods for screening and diagnosing herpes simplex virus (HSV) type 1 and 2. The aim of this study was to analyze the reliability, accuracy, and usefulness of the new assay HSV OligoGen kit in comparison with the Roche LightCycler HSV 1/2 Qual Kit assay for the detection of HSV in clinical samples. For this analysis, a prospective study was designed for detection of HSV-1 and HSV-2 including 110 ulcer specimens, 48 urine, 48 endocervical, 43 cerebral spinal fluids, 4 urethral and 3 pharyngeal swabs that were sent from a regional STI clinic or an Intensive Clinical Unit, both in Seville, Spain. In comparison to the Roche LightCycler HSV 1/2 Qual Kit assay, sensitivity, specificity, positive and negative predicative values, and kappa value for HSV detection using the HSV OligoGen kit were 96.2%, 100%, 100%, 98.3%, and 0.97 for HSV-1, respectively. For HSV-2, the corresponding values were 98.3%, 100%, 100%, 99.5%, and 0.98, respectively. Statistical data obtained in this study confirms the usefulness and reliable results of this new assay. PMID- 27185645 TI - Real time application of whole genome sequencing for outbreak investigation - What is an achievable turnaround time? AB - Whole genome sequencing (WGS) is increasingly employed in clinical settings, though few assessments of turnaround times (TAT) have been performed in real time. In this study, WGS was used to investigate an unfolding outbreak of vancomycin resistant Enterococcus faecium (VRE) among 3 patients in the ICU of a tertiary care hospital. Including overnight culturing, a TAT of just 48.5 h for a comprehensive report was achievable using an Illumina Miseq benchtop sequencer. WGS revealed that isolates from patient 2 and 3 differed from that of patient 1 by a single nucleotide polymorphism (SNP), indicating nosocomial transmission. However, the unparalleled resolution provided by WGS suggested that nosocomial transmission involved two separate events from patient 1 to patient 2 and 3, and not a linear transmission suspected by the time line. Rapid TAT's are achievable using WGS in the clinical setting and can provide an unprecedented level of resolution for outbreak investigations. PMID- 27185647 TI - Tuning the Receding Contact Angle on Hydrogels by Addition of Particles. AB - Control of the swelling, chemical functionalization, and adhesivity of hydrogels are finding new applications in a wide range of material systems. We investigate experimentally the effect of adsorbed particles on hydrogels on the depinning of contact lines. In our experiments, a water drop containing polystyrene microspheres is deposited on a swelling hydrogel, which leads to the drop absorption and particle deposition. Two regimes are observed: a decreasing drop height with a pinned contact line followed by a receding contact line. We show that increasing the particles concentration increases the duration of the first regime and significantly decreases the total absorption time. The adsorbed particles increase the pinning force at the contact line. Finally, we develop a method to measure the receding contact angle with the consideration of the hydrogel swelling. PMID- 27185646 TI - Hierarchical Porous LiNi1/3Co1/3Mn1/3O2 Nano-/Micro Spherical Cathode Material: Minimized Cation Mixing and Improved Li(+) Mobility for Enhanced Electrochemical Performance. AB - Although being considered as one of the most promising cathode materials for Lithium-ion batteries (LIBs), LiNi1/3Co1/3Mn1/3O2 (NCM) is currently limited by its poor rate performance and cycle stability resulting from the thermodynamically favorable Li(+)/Ni(2+) cation mixing which depresses the Li(+) mobility. In this study, we developed a two-step method using fluffy MnO2 as template to prepare hierarchical porous nano-/microsphere NCM (PNM-NCM). Specifically, PNM-NCM microspheres achieves a high reversible specific capacity of 207.7 mAh g(-1) at 0.1 C with excellent rate capability (163.6 and 148.9 mAh g(-1) at 1 C and 2 C), and the reversible capacity retention can be well maintained as high as 90.3% after 50 cycles. This excellent electrochemical performance is attributed to unique hierarchical porous nano-/microsphere structure which can increase the contact area with electrolyte, shorten Li(+) diffusion path and thus improve the Li(+) mobility. Moreover, as revealed by XRD Rietveld refinement analysis, a negligible cation mixing (1.9%) and high crystallinity with a well-formed layered structure also contribute to the enhanced C-rates performance and cycle stability. On the basis of our study, an effective strategy can be established to reveal the fundamental relationship between the structure/chemistry of these materials and their properties. PMID- 27185648 TI - Biomechanical Evaluation of a Novel Integrated C1 Laminar Hook Combined with C1 C2 Transarticular Screws for Atlantoaxial Fusion: An In Vitro Human Cadaveric Study. AB - OBJECTIVE: To evaluate the acute stability of a novel integrated C1 laminar hook (H) combined with a C1-C2 transarticular screw (TAS) with established techniques. METHODS: A novel integrated C1 laminar hook was tested. Seven human cadaveric cervical spines (C0-C3) were used. The range of motion (ROM) of C1-C2 during flexion-extension, lateral bending, and axial rotation were recorded. The specimens were tested under the following conditions: intact, destabilized (using a type II odontoid fracture model), and destabilized but with internal fixation. The following screw systems were used: bilateral C1-C2 TAS combined with the Gallie (G) technique (TAS+G), C1-C2 TAS combined with a novel integrated C1 laminar hook (TAS+H), C1 lateral mass screw and C2 pedicle screws (C2PS+C1LMS), and novel integrated C1 laminar hook combined with C2 pedicle screws (C2PS+H). The TASs were always inserted after the C2PSs. The C2PS+C1LMS and C2PS+H tests were performed alternatively, as were the TAS+G and TAS+H tests. RESULTS: All fixation constructs greatly improved acute atlantoaxial stability, with no significant difference among TAS+H, TAS+G, and C2PS+C1LMS (all P > 0.05). C2PS+H showed the greatest C1-C2 ROM in axial rotation, significantly different from TAS+G, C2PS+C1LMS, and TAS+H fixation models (all P < 0.05). However, there were no significant differences between C2PS+H and the other 3 models in flexion extension and lateral bending (all P > 0.05). CONCLUSIONS: The TAS+H technique can achieve acute stability comparable to that with the TAS+G technique for treating C1-C2 instability. The C2PS+H is a promising alternative, although it provides less stability in axial rotation than TAS+G, TAS+H, or C2PS+C1LMS. PMID- 27185649 TI - Intradural Extramedullary Capillary Hemangioma in the Upper Cervical Spine: First Report. AB - BACKGROUND: The occurrence of intradural extramedullary capillary hemangiomas is exceedingly rare. To date, only 39 cases of intradural extramedullary capillary hemangiomas have been reported in the English literature, and all of these cases have been described at the lumbar and thoracic spinal levels. To our knowledge, this report is the first case of capillary hemangiomas of the cervical spine in the literature. In general, this entity is misdiagnosed preoperatively as a neoplasm. CASE DESCRIPTION: A 29-year-old man presented with neck pain and progressive gait disturbance, and was diagnosed with an intradural extramedullary capillary hemangioma in the cervical region. CONCLUSIONS: Although rare, our case demonstrates that capillary hemangioma should be considered in the differential diagnosis of intradural extramedullary tumor of the cervical spine. PMID- 27185650 TI - Posttreatment Apparent Diffusion Coefficient Changes in the Periresectional Area in Patients with Glioblastoma. AB - BACKGROUND: Although targeted by radiotherapy, recurrence in glioblastoma occurs mainly periresectionally owing to tumor infiltration. An increase in the apparent diffusion coefficient (ADC) has been shown in the large high-T2 area on magnetic resonance imaging posttreatment; however, until now ADC has not been investigated directly in the more relevant periresectional area. METHODS: Histogram analysis was used to assess periresectional ADC values in patients with glioblastoma postradiotherapy versus preradiotherapy. Periresectional ADC values starting at 0 5 mm in 5-mm increments up to 20-25 mm were extracted and compared using 2-way repeated-measurements analysis of variance. RESULTS: Mean ADC values directly adjacent to the resection area (0-5 mm) were significantly higher postradiotherapy compared with preradiotherapy (P = .017). ADC values in the 0- to 5-mm region were also higher than those in 5- to 10-, 10- to 15-, and 15- to 20-mm regions (P < .05). Regional standard deviations in ADC values were higher postradiotherapy compared with preradiotherapy for the 0- to 5-mm region up to the 15- to 20-mm region, inclusive (P < .05); however, Cox regression analysis showed no survival benefits from the increased ADC in the 0- to 5-mm region postradiotherapy. CONCLUSIONS: Increased ADC values, representing a decrease in infiltrative tumor load, were demonstrated in a limited direct periresectional area. This finding adds to previous studies evaluating ADC response in the larger high-T2 area in relation to survival. PMID- 27185651 TI - Mirror Aneurysms Among Multiple Aneurysms: Lesser of the Two Evils. AB - BACKGROUND: To highlight the management nuances in addressing mirror aneurysms (MirAns) in a subset of multiple aneurysms. METHODS: A retrospective study was carried out and all multiple intracranial aneurysms (n = 70) over 9 years were identified. Exclusion criteria were associated arteriovenous malformations, moyamoya disease, and either traumatic or mycotic aneurysms or those managed by endovascular approach alone. Patients were grouped as MirAn and nonmirror aneurysms (nMirAns). Outcome was assessed by Glasgow Outcome Score at 1 month. The Pearson chi(2) test or Fisher exact test were used to establish association. RESULTS: MirAns (n = 17) accounted for 2.1% of all intracranial aneurysms and 24.3% of multiple aneurysms. Female predilection was eminent in the MirAn group (3.25:1) compared with the nMirAn group (2.5:1). The middle cerebral artery (n = 6) followed by the internal carotid artery-posterior communicating artery (n = 5) were the most common sites of the MirAns. There was no significant difference between the 2 groups for hypertension or age (MirAn, 52 years [+/- 11.231]; hypertension, 52.9%; nMirAn, 48.58 years [+/- 12.97]; hypertension, 54.7%). There was a definite trend towards less intraoperative rupture (MirAn, 4/17; nMirAn, 27/53; P = 0.048), decreased intraoperative vasospasm (MirAn, 1; nMirAn, 11) in the MirAn group. Development of infarct was significantly less in the MirAn group (P = 0.027) with a better outcome (13 in MirAn and 26 in nMirAn had good outcome; P = 0.048). CONCLUSIONS: MirAns are not significantly associated with risk factors such as age, hypertension, and diabetes. Intraoperative rupture, vasospasm, and infarct are less common, with a tendency towards better neurologic outcome compared with nMirAns. PMID- 27185652 TI - Implementing Routine Head Circumference Measurements in Addis Ababa, Ethiopia: Means and Challenges. AB - OBJECTIVE: A substantial number of infants in Ethiopia suffer from hydrocephalus. Neurosurgical expertise has until recently been virtually nonexistent in the country; however, since 2006, a neurosurgery training program has been established in Addis Ababa, where hydrocephalus surgery now is performed in 3 hospitals. Our experience is that hydrocephalus is diagnosed and treatment is too late to avoid severe brain damage. Introducing routine head circumference (HC) measurements can ease the detection of hydrocephalus and thus lead to earlier diagnosis, thereby reducing the brain damage caused by the condition. The present pilot project had two major aims: to get the process of implementation started and to gain experience with how this implementation best can be achieved. METHODS: We educated and encouraged the nurse staff members of 12 randomly selected health (mother and child) clinics in Addis Ababa in performing HC measurements, using a recently developed Ethiopian HC chart. Much of the work was related to follow-up. A local Ethiopian healthcare worker was employed to lead the follow-up and to continue the implementation in the remaining 14 clinics. RESULTS: During our attempted implementation of routine HC measuring, we encountered a line of administrational, cultural, infrastructural, and didactic problems and challenges, which are discussed. CONCLUSIONS: The experience we have gained during this pilot project will be used in further development and implementation of routine HC measuring throughout Ethiopia. These experiences may be of interest and use to others wanting to introduce similar routines in low income countries. PMID- 27185654 TI - A Challenge for Leadership: Elevating Awareness Versus Tolerating Ignorance. PMID- 27185653 TI - Presigmoid Approach to Vertebrobasilar Artery Aneurysms: A Series of 31 Patients and Review of the Literature. AB - OBJECTIVE: The presigmoid approach can be used to treat vertebrobasilar artery aneurysms when circumstances require more operative exposure. High morbidity and mortality in these cases have been reported. In this study, we describe our modified presigmoid approach for vertebrobasilar artery aneurysms and our clinical results. METHODS: This series includes patients with vertebrobasilar aneurysms clipped via the modified presigmoid approach at the Department of Neurosurgery at Helsinki University Hospital from 1998 to 2014. Data were collected from the operating record books, patients' medical records, and a radiologic database server. RESULTS: Thirty-three presigmoid procedures of 31 patients were performed to treat 34 aneurysms (14 ruptured, 20 unruptured). The aneurysms had a mean distance from the posterior clinoid process to the aneurysm neck of 12.2 mm (range, 0-26.6 mm). A favorable outcome was achieved in 21 patients (64%). A favorable outcome was achieved in 74% of unruptured and good grade patients, whereas favorable outcome was achieved in only 36% of poor-grade patients. Complete or near-complete occlusion was achieved in 79%. Larger aneurysms, fusiform morphology, and anterior dome projection had lower occlusion rates. CONCLUSIONS: We have described our experiences of using the presigmoid approach to treat vertebrobasilar aneurysms. The clinical and radiographic results are acceptable given the complex location and configuration of the treated aneurysms. Unfavorable outcomes are related to the poor admission Hunt and Hess grade, aneurysm morphology, and aneurysm size. PMID- 27185655 TI - Stokes and anti-Stokes luminescence in Tm(3+)/Yb(3+)-doped Lu3Ga5O12 nano garnets: a study of multipolar interactions and energy transfer dynamics. AB - Nanocrystalline Lu3Ga5O12 garnets doped with Tm(3+)/Yb(3+) ions have been synthesized by a low cost and environmentally benign sol-gel technique and characterized for their structural, Stokes and anti-Stokes luminescence properties. The diffuse reflectance spectra of doped Lu3Ga5O12 nano-garnets have been measured to derive the partial energy level structure of Tm(3+) and Yb(3+) ions and possible energy transfer channels between them. Upon laser excitation at 473 nm, weak red and intense near-infrared Stokes emissions have been observed in the nano-garnets. The decay curves of (3)H4 and (1)G4 levels of Tm(3+) ions and the (2)F5/2 level of Yb(3+) ions have been measured upon resonant laser excitation and are found to be non-exponential in nature due to multipolar interactions. In order to know the kind of multipolar interaction among optically active ions, the decay curves are analyzed through the generalized Yokota Tanimoto model. Moreover, under 970 nm laser excitation, intense blue anti-Stokes emission is observed by the naked eye in Tm(3+)-Yb(3+) co-doped Lu3Ga5O12 nano garnets. The results show that as-synthesized nano-garnets may be useful in the field of phosphors and photonics. PMID- 27185656 TI - Self-current induced spin-orbit torque in FeMn/Pt multilayers. AB - Extensive efforts have been devoted to the study of spin-orbit torque in ferromagnetic metal/heavy metal bilayers and exploitation of it for magnetization switching using an in-plane current. As the spin-orbit torque is inversely proportional to the thickness of the ferromagnetic layer, sizable effect has only been realized in bilayers with an ultrathin ferromagnetic layer. Here we demonstrate that, by stacking ultrathin Pt and FeMn alternately, both ferromagnetic properties and current induced spin-orbit torque can be achieved in FeMn/Pt multilayers without any constraint on its total thickness. The critical behavior of these multilayers follows closely three-dimensional Heisenberg model with a finite Curie temperature distribution. The spin torque effective field is about 4 times larger than that of NiFe/Pt bilayer with a same equivalent NiFe thickness. The self-current generated spin torque is able to switch the magnetization reversibly without the need for an external field or a thick heavy metal layer. The removal of both thickness constraint and necessity of using an adjacent heavy metal layer opens new possibilities for exploiting spin-orbit torque for practical applications. PMID- 27185657 TI - Role of the mTOR Signalling Pathway in Experimental Rabbit Vein Grafts. AB - BACKGROUND: Coronary artery bypass grafting is employed for the treatment of multiple-vessel lesions. Studies have shown that continued maladaptive remodelling expedites atherosclerosis and that excessive remodelling leads to graft restenosis. However, few studies have focussed on mechanistic target of rapamycin (mTOR) signalling involved during remodelling of transplanted veins. METHODS: Rabbits were randomly allocated to groups undergoing vein-graft restenosis or sham surgery. At 1, 3, 7, 14, 28 and 90 days after surgery, we removed bypassed grafts and placed them in groups named T1, T2, T3, T4, T5 and T6, respectively. Group T0 denoted the control group. Analysis included vessel thickness, electron microscope data, TUNEL staining, and expression of the proliferation-associated gene proliferating cell nuclear antigen (PCNA). We chose specific time-points of gene expression, and then observed changes in the mTOR signalling. RESULTS: The early stage of vein grafting (one to three days after surgery) led to apoptosis and degradation of the extracellular matrix. Seven days after surgery, cells began to proliferate. RICTOR expression in mTOR complex 2 (mTORC2) and that of its downstream substrate protein kinase C was enhanced in the early stage (T1 and T3), and was higher in T1. mTORC1's upstream gene regulation decreased in T1 and increased in T3. Its downstream genes eIF4b and 4E BP showed similar changes. Expression of eIF4e and eIF4b increased, and led to an increase in protein composition. CONCLUSIONS: After transplantation, mTORC1 function and its upstream and downstream genes were inhibited on the first day after grafting, but mTORC2 function was enhanced. One week after surgery, mTORC2 was still overexpressed when mTORC1 function had recovered and became enhanced. Hence, mTORC2 plays a major role in arterialisation of veins. PMID- 27185658 TI - Roles of T-cell Immunoglobulin and Mucin Domain Genes and Toll-like Receptors in Wheezy Children with Mycoplasma pneumoniae Pneumonia. AB - BACKGROUND: The study aimed to explore possible factors influencing wheezing in children with Mycoplasma pneumoniae pneumonia (MPP). METHODS: The study included 84 children with MPP, who were divided into two groups: wheezy group (n=40) and non-wheezy group (n=44), along with 30 age-matched healthy controls. T-cell immunoglobulin and mucin domain gene (Tim) 1, 3 and Toll-like receptor (TLR) 2, 4 were evaluated using RT-PCR. Serum IL-10, TNF-alpha, IFN-gamma and IgE were assessed by enzyme-linked immunosorbent assay. Peripheral blood eosinophil (EOS) was measured by an automated haematology. RESULTS: Children with MPP had markedly increased TLR2, TLR4, Tim1, IL-10, TNF-alpha, IgE and EOS, and decreased IFN gamma than the healthy controls. In the presence of MPP, wheezy children had significantly elevated TLR2, Tim1, Tim3, TNF-alpha, IgE and EOS than non-wheezy children. In wheezy children with MPP, MP-specific antibody titre was positively correlated with TLR2 and TIM1, and negatively correlated with IFN-gamma. IgE was positively correlated with TLR2, TLR4 and Tim1, while EOS was positively correlated with Tim1 and Tim3. CONCLUSION: TLR2, Tim1, Tim3, TNF-alpha, IgE and EOS play a role in MPP-related wheezing in children. The role of IgE might be associated with TLR2 and Tim1, and the role of EOS might be associated with Tim1 and Tim3. PMID- 27185659 TI - Imperatorin exerts antiallergic effects in Th2-mediated allergic asthma via induction of IL-10-producing regulatory T cells by modulating the function of dendritic cells. AB - Imperatorin is a furanocoumarin compound which exists in many medicinal herbs and possesses various biological activities. Herein, we investigated the antiallergic effects of imperatorin in asthmatic mice and explored the immunomodulatory actions of imperatorin on immune cells. We used a murine model of ovalbumin (OVA) induced asthma to evaluate the therapeutic potential of imperatorin. Additionally, bone marrow-derived dendritic cells (DCs; BMDCs) were used to clarify whether imperatorin exerts an antiallergic effect through altering the ability of DCs to regulate T cells. Oral administration of imperatorin to OVA sensitized and -challenged mice decreased serum OVA-specific immunoglobulin E (IgE) production, attenuated the airway hyperresponsiveness (AHR), and alleviated airway inflammation in a dose-dependent manner. Notably, secretions of Th2 cytokines and chemokines were reduced, and numbers of interleukin (IL)-10 producing regulatory T cells (Tregs) increased in imperatorin-treated mice. Imperatorin inhibited proinflammatory cytokines and IL-12 production but enhanced IL-10 secretion by lipopolysaccharide (LPS)-stimulated BMDCs. Compared to fully mature DCs, imperatorin-treated DCs expressed high levels of the inducible costimulatory ligand (ICOSL) and Jagged1 molecules, and had the regulatory capacity to promote the generation of IL-10-producing CD4(+) T cells in vitro. Additionally, imperatorin directly suppressed activated CD4(+) T-cell proliferation and cytokine production. Imperatorin may possess therapeutic potential against Th2-mediated allergic asthma not only via stimulating DC induction of Tregs but also via direct inhibition of Th2 cell activation. These findings provide new insights into how imperatorin affects the Th2 immune response and the development of imperatorin as a Treg-type immunomodulatory agent to treat allergic asthma. PMID- 27185660 TI - [Assessment of a 3D digital orthoptic test platform]. AB - PURPOSE: To compare standard orthoptic tests with a novel digital 3D orthoptic platform, 3DeltaEasy((c)) from Orthoptica((r)). MATERIALS AND METHODS: This study tests the 3D digital orthoptics platform, 3DeltaEasy((c)) from Orthoptica((r)) and compares it to the corresponding standard orthoptic tests. This platform consists of a computer equipped with dedicated software, a video projector and 3D liquid crystal glasses. Three tests were compared: Wirt test, measurement of horizontal and vertical phorias, and the horizontal fusional amplitude in convergence and divergence. A total of 102 subjects, 53 males (52 %) and 49 females (48 %), aged between 9 years and 72 years (mean age 33+/-16.4 years) were examined at the ophthalmologic department of the Brest Hospital (France) and included in this observational cross-sectional study. Subjects recruited in this study were patients requiring orthoptic screening or therapy. Patients without their optimal visual corrections were excluded. All patients underwent both ophthalmological and orthoptic examination including Wirt fly stereotest with polarizing spectacles, cover tests to evaluate and measure the horizontal and vertical deviation of the lines of sight, horizontal vergence ranges using prism bar and their equivalent tests implemented in the digital 3D orthoptic tests 3DeltaEasy((c)) from Orthoptica((r)). RESULTS: All data were processed using MedCalc Statistical Software version 14.12.0 (MedCalc Software bvba, Ostend, Belgium). The main result of this study is that 3DeltaEasy((c)) and the classical Wirt test are correlated (Spearman's coefficient of rank correlation: rho=0.74; P<0.0001), cover tests are equivalent for intermediate and far vision (paired t test; P=0.46 and P=0.51), and horizontal and vertical vergence range are comparable for distance vision (paired t-test; P=0.34 and P=0.94). CONCLUSION: New digital 3D tools could easily substitute for some orthoptic tests with better ergonomics. Eventually, by increasing the number of tests performed, it could substitute for nearly all tests. PMID- 27185661 TI - [Eales' disease]. AB - The syndrome of recurrent vitreous hemorrhages in young men was described for the first time by Henry Eales in 1880. The association with a clinical manifestation of ocular inflammation was reported 5years later. Eales disease affects young adults who present with ischemic retinal vasculitis, with the peripheral retina most commonly affected. Most cases have been reported in South Asia. Although the etiology of this abnormality is unknown, it may be related to an immune sensitivity to Mycobacterium tuberculosis antigens. Its pathogenesis is related to extensive ischemia that affects the retina, secondary to an obliterative retinal vasculopathy with release of angiogenic factors of the VEGF type. Involvement of the retina is the hallmark of the disease, which manifests as follows: periphlebitis, retinal capillary ischemia most often affecting the periphery with secondary proliferative retinopathy and retinal and/or papillary neovascularization, recurrent vitreous hemorrhages and tractional retinal detachment. These complications are potentially blinding. The natural history of Eales disease varies, with temporary or permanent remission in some cases and continuous progression in others. Progression is often bilateral, which necessitates regular follow-up. The treatment of Eales disease depends on the stage of the disease and is not well defined. Observation only, pars plana vitrectomy surgery and/or intravitreal injections of anti-VEGF are recommended in cases of vitreous hemorrhage, associated with corticosteroids when retinal vasculitis is present. Laser pan-retinal photocoagulation is necessary when neovascularization is present. PMID- 27185662 TI - [Electronic eikonometer: Measurement tests displayed on stereoscopic screen]. AB - We propose the presentation on a stereoscopic screen of the electronic eikonometer tests intended for analysis and measurement of perceptual effects of binocular disparity. These tests, so-called "built-in magnification tests" are constructed according to the same principle as those of preceding eikonometers (disparity variation parameters being included in each test presentation, which allows, for test observation and measurements during the examination, the removing of any intermediate optical system). The images of these tests are presented separately to each eye, according to active or passive stereoscopic screen technology: (1) Ogle Spatial Test to measure aniseikonia; (2) Fixation Disparity test: binocular nonius; (3) retinal correspondence test evaluated by nonius horopter; (4) stereoscopic test using Julesz' random-dot stereograms (RDS). All of these tests, with their variable parameters included, are preprogrammed by means of an associated mini-computer. This new system (a single screen for the presentation of tests for the right eye and left eye) will be much simpler to reproduce and install for all practitioners interested in the functional exploration of binocular vision. We develop the suitable methodology adapted to each type of examination, as well as manipulations to be performed by the operator. We then recall the possibilities for reducing aniseikonia thanks to some theoretical studies previously performed by matrix calculation of the size of the retinal images for different types of eye (emmetropia, axial or conformation anisometropia, aphakia) and for different means of correction (glasses, contact lenses, implants). Software for achieving these different tests is available, on request, at this address: eiconometre.electronique@gmail.com. PMID- 27185664 TI - Australian GPs warn patients of funding cuts through prescription campaign. PMID- 27185663 TI - Increased aerobic glycolysis is important for the motility of activated VSMC and inhibited by indirubin-3'-monoxime. AB - Increased aerobic glycolysis is a recognized feature of multiple cellular phenotypes and offers a potential point for drug interference, as pursued by anti tumor agents targeting the Warburg effect. This study aimed at examining the role of aerobic glycolysis for migration of vascular smooth muscle cells (VSMC) and its susceptibility to the small molecule indirubin-3'-monoxime (I3MO). Activation of VSMC with platelet-derived growth factor (PDGF) resulted in migration and increased glycolytic activity which was accompanied by an increased glucose uptake and hexokinase (HK) 2 expression. Inhibition of glycolysis or hexokinase by pharmacological agents or siRNA-mediated knockdown significantly reduced the migratory behavior in VSMC without affecting cell viability or early actin cytoskeleton rearrangement. I3MO, previously recognized as inhibitor of VSMC migration, was able to counteract the PDGF-activated increase in glycolysis and HK2 abundance. Activation of signal transducer and activator of transcription (STAT) 3 could be identified as crucial event in upregulation of HK2 and glycolytic activity in PDGF-stimulated VSMC and as point of interference for I3MO. I3MO did not inhibit hypoxia-inducible factor (HIF)1alpha-dependent transcription nor influence miRNA 143 levels, other potential regulators of HK2 levels. Overall, we demonstrate that increased aerobic glycolysis is an important factor for the motility of activated VSMC and that the anti-migratory property of I3MO may partly depend on impairment of glycolysis via a compromised STAT3/HK2 signaling axis. PMID- 27185665 TI - Prospect of quantum anomalous Hall and quantum spin Hall effect in doped kagome lattice Mott insulators. AB - Electronic states with non-trivial topology host a number of novel phenomena with potential for revolutionizing information technology. The quantum anomalous Hall effect provides spin-polarized dissipation-free transport of electrons, while the quantum spin Hall effect in combination with superconductivity has been proposed as the basis for realizing decoherence-free quantum computing. We introduce a new strategy for realizing these effects, namely by hole and electron doping kagome lattice Mott insulators through, for instance, chemical substitution. As an example, we apply this new approach to the natural mineral herbertsmithite. We prove the feasibility of the proposed modifications by performing ab-initio density functional theory calculations and demonstrate the occurrence of the predicted effects using realistic models. Our results herald a new family of quantum anomalous Hall and quantum spin Hall insulators at affordable energy/temperature scales based on kagome lattices of transition metal ions. PMID- 27185666 TI - Compartment syndrome in a patient treated with perineural liposomal bupivacaine (Exparel). AB - Acute compartment syndrome is a condition that may result in sensorimotor deficits and loss of function of the affected limb as a result of ischemic injury. It is considered a surgical emergency and prompt diagnosis and treatment results in more favorable outcomes. The use of regional anesthesia is controversial in patients at risk for compartment syndrome due to concern of its potential to mask symptoms of the condition. A 44-year-old African American male presented to surgery for open reduction and internal fixation of a comminuted distal radius fracture. As part of an off-label, investigator-initiated, and institutional review board-approved study, he received a perineural injection of liposomal bupivacaine (Exparel) around the median, ulnar, and radial nerves at the level of the proximal forearm. The following morning, his initial complaints of numbness and incisional pain progressively evolved into worsening numbness, diffuse discomfort, and pain with passive movement. A diagnosis of compartment syndrome was made and he underwent an emergency fasciotomy. The diagnosis of compartment syndrome requires a high index of suspicion and prompt treatment. This patient's changing pattern of symptoms-rather than his pain complaints alone resulted in the diagnosis of compartment syndrome treated with emergent fasciotomy in spite of finger numbness that was initially attributed to the liposomal bupivacaine. While the use of liposomal bupivacaine did not preclude the diagnosis of compartment syndrome in our patient, it should be used with caution in patients at risk for compartment syndrome until additional data, particularly regarding block characteristics, are available. PMID- 27185667 TI - Improving the quality of the operating room to intensive care unit handover at an urban teaching hospital through a bundled intervention. AB - STUDY OBJECTIVE: To evaluate the efficacy of a bundled intervention to improve the quality of the operating room to intensive care unit (ICU) clinical handover. DESIGN: Prospective, interventional study. SETTING: An urban, public teaching hospital with more than 1500 direct postoperative ICU admissions each year. INTERVENTIONS: A bundled intervention to include the addition of a direct anesthesia provider to ICU nurse telephone report, a mnemonic to standardize the handover process, and improved template for postoperative documentation by the anesthesia team. MEASUREMENTS: Preintervention (baseline) and postintervention survey data were solicited from key stakeholders, which included anesthesia providers and ICU nursing staff. MAIN RESULTS: Anesthesia provider and ICU nursing staff satisfaction levels rose significantly following implementation of the bundled intervention. In addition, perceived effectiveness of the handover process and note increased significantly. The satisfaction level of the ICU nurses with respect to the phone report received before patient arrival in the ICU nearly doubled. CONCLUSIONS: The implementation of a bundled handover intervention was associated with increased stakeholder satisfaction as well as a perception of increased efficacy and quality of the overall handover process and postoperative anesthesia documentation. PMID- 27185668 TI - Median effective concentration of remifentanil in target controlled infusion for smooth tracheal extubation during emergence from general anesthesia in elderly patients. AB - STUDY OBJECTIVE: To determine the median effective concentration (EC50) of remifentanil during targeted-controlled infusion for smooth tracheal extubation during emergence from total intravenous anesthesia in elderly patients. DESIGN: Prospective, Dixon up-and-down method. SETTING: Postoperative emergence. PATIENTS: Twenty-four American Society of Anesthesiologists grade I-II female elderly patients undergoing elective jaw cyst surgery. INTERVENTIONS: The EC50 of remifentanil for smooth emergence was calculated by the Dixon up-and-down method. MEASUREMENTS: The EC50 and 95% confidence intervals were analyzed by probit analysis using logistic regression. Vital signs (mean arterial pressure, heart rate, oxygen saturation, and end-tidal carbon dioxide partial pressure), postanesthesia recovery score, visual analogue pain scale, and adverse effects were monitored. Mean arterial pressure and heart rate were compared between patients with smooth extubation vs those with failed smooth extubation. MAIN RESULTS: The Dixon up-and-down method showed that the EC50 of remifentanil for smooth tracheal extubation during emergency from anesthesia was 0.94 ng/mL in female elderly patients. The probit analysis showed that the EC50 of remifentanil was 0.99 ng/mL (95% confidence interval, 0.52-1.51 ng/mL). Heart rate and mean arterial pressure were significantly lower in patients with smooth extubation as compared with those with failed smooth extubation at 0 minute (at extubation) as well as 1 and 5 minutes after extubation (P< .05). CONCLUSIONS: Target infusion of remifentanil at 0.94 ng/mL could effectively inhibit tracheal extubation related cough response and cardiovascular responses in 50% of the female elderly patients without delaying recovery from anesthesia, which could ensure smooth tracheal extubation during emergence from anesthesia. PMID- 27185669 TI - Opioid consumption in total knee arthroplasty patients: a retrospective comparison of adductor canal and femoral nerve continuous infusions in the presence of a sciatic nerve catheter. AB - OBJECTIVE: To compare opioid consumption among patients who receive a continuous adductor canal block (ACB) versus continuous femoral nerve block (FB) for total knee arthroplasty analgesia in the presence of an intermittent sciatic nerve catheter (iSB). DESIGN: Matched cohort retrospective study. SETTING: Mayo Clinic, Jacksonville, FL. PATIENTS: Ninety patient charts were included in this study: 45 patients with continuous ACB/iSB and 45 with continuous FB/iSB. Patients were matched according to mean preoperative opioid consumption and pain scores, BMI, age, and gender. MEASUREMENTS: The primary outcome of the study was postoperative on-demand opioid consumption on postoperative days 0 (POD 0), 1 (POD 1), and 2 (POD 2). Secondary outcomes included postoperative Visual Analog Scale (VAS) scores for anterior and posterior knee pain, incidence of nausea and pruritus, need for intravenous rescue opioid, and need for catheter bolus by a physician. MAIN RESULTS: On POD 0, mean opioid consumption in milligrams of oral morphine equivalent [mean+/-SD (95% CI)] was 43.98mg+/-33.36 (33.96, 54) in the ACB/iSB group vs 38.45mg+/-30.99 (29.14, 47.76) in the FB/iSB group, respectively (P=.42); on POD 1, 74.96mg+/-37.23 (63.78, 86.14) vs 72.40mg+/-62.34 (53.67, 91.13) (P=.81); on POD 2, 28.19mg+/-17.69 (22.87, 33.51) vs 31.84mg+/-23.09 (24.90, 38.78) (P=.40). On POD 1, median anterior knee VAS scores at rest were equivalent in both the ACB/iSB and FB/iSB groups (1 vs 1, respectively, P=.46); however, patients in the ACB/iSB group were more likely to have higher anterior knee pain scores with movement (4 vs 1, P=.002). CONCLUSION: In the first 2 days after a total knee arthroplasty, opioid consumption in patients with continuous ACB/iSB was not significantly different from patients receiving continuous FB/iSB. Continuous adductor canal block appears to provide adequate analgesia when compared to continuous femoral blockade. PMID- 27185671 TI - Endotracheal intubation training for clinical trainees in Japan-is the anesthesiology training not necessary? PMID- 27185670 TI - Remifentanil and worse patient-reported outcomes regarding postoperative pain management after thyroidectomy. AB - BACKGROUND: Intraoperative remifentanil has been associated with postoperative hyperalgesia, higher visual analogic pain scores, and increased postoperative morphine consumption. However, this has not been investigated from patient's perspective by using a patient-reported outcomes (PROs) approach with a validated questionnaire. METHODS: We joined the largest prospective observational study on postoperative pain, PAIN OUT Project (NCT02083835), and collected data for 2 years. We studied the effects of remifentanil (R+) vs nonremifentanil (R-) anesthesia on PROs regarding their pain management after elective thyroidectomy. We selected 5 primary PROs (worst pain experienced, time spent in severe pain, relief received by treatment, satisfaction about pain management, wish for more pain treatment) and five secondary PROs (drowsiness, itching, nausea, dizziness, waking up due to pain) from the validated International Pain Outcomes questionnaire. RESULTS: The analysis included 317 patients, 208 in the R+ group (65.6%) and 109 in the R- group (34.4%), the latter receiving fentanyl as intraoperative opioid. Although the R+ group received more frequently intraoperative nonopioids (202/208, 97.1% vs 86/109, 78.9%; P < .0001) and opioids (184/208, 88.5% vs 38/109, 34.9%; P < .001), it reported higher worst pain (5.1+/-2.1 vs 4.3+/-2.1, P < .005), lower satisfaction (7.4+/-2.0 vs 8.1+/ 2.1, P < .001), and worse results in 4 secondary PROs. A sensitivity analysis performed matching 67 couples of patients yielded similar results in primary PROs. CONCLUSIONS: Our study suggests that remifentanil-based anesthesia is associated with worse pain-related PROs in patients undergoing thyroidectomy despite more frequent intraoperative analgesic administration. This study adds further evidence to the growing literature about opioid- and remifentanil-induced hyperalgesia. PMID- 27185672 TI - The ultrasound-guided continuous transmuscular quadratus lumborum block is an effective analgesia for total hip arthroplasty. PMID- 27185673 TI - Anesthesia management and sugammadex experience in a neonate for Galen vein aneurysm. PMID- 27185675 TI - Opioids and postoperative shivering. PMID- 27185674 TI - Near-infrared spectroscopy provides continuous monitoring of compromised lower extremity perfusion during cardiac surgery. AB - Near-infrared spectroscopy (NIRS) is more frequently used to monitor regional oxygenation/perfusion of the cerebral and somatorenal vascular bed during congenital heart surgery. However, NIRS probes can be placed elsewhere to assess regional perfusion. We report the intraoperative use of NIRS probes on both calves of an infant to continuously monitor changes in the regional oxygenation/perfusion of a lower extremity whose perfusion was compromised after femoral arterial line placement. The NIRS trend of the compromised limb was compared with the contralateral limb throughout congenital heart surgery including the period on cardiopulmonary bypass (CPB). Our case report illustrates that NIRS technology can be used to monitor ongoing lower extremity vascular compromise during congenital heart surgery when it is not practical to directly access and continuously assess the limb. Transient vascular compromise after invasive femoral arterial line or sheath placement for cardiac catheterization in small infants is not infrequent. NIRS technology in such circumstances may help to decide whether watchful waiting is acceptable or immediate interventions are indicated. Continuous NIRS monitoring showed that limb regional oxygenation remained depressed during CPB but dramatically increased in the post-CPB period. PMID- 27185676 TI - Shaving and clopidogrel in elderly: shouldwe be worried? PMID- 27185677 TI - Comparison of the C-MAC video laryngoscope to a flexible fiberoptic scope for intubation with cervical spine immobilization. AB - STUDY OBJECTIVE: To compare the C-MAC video laryngoscope to the standard flexible fiberoptic scope (FFS) with an eye piece (but without a camera or a video screen) for intubation of patients undergoing cervical spine surgery with manual inline stabilization. The primary end point was the time to achieve successful tracheal intubation. Secondary end points included glottic view at intubation and number of intubation attempts. DESIGN: Prospective, randomized, single-blinded study. SETTING: Cedars Sinai Medical Center in Los Angeles, CA. PATIENTS: One hundred forty patients (American Society of Anaesthesiologists physical status I-III), aged 18 to 80years undergoing elective cervical spine surgery. INTERVENTION: Patients were prospectively randomized to undergo tracheal intubation using either an FFS (n=70) or the C-MAC video laryngoscope (n=70). MEASUREMENTS: After performing a preoperative airway evaluation, patients underwent a standardized induction sequence. The glottic view was assessed at the time of tracheal tube placement using the Cormack-Lehane and percentage of glottic opening scoring systems. In addition, the time required for successful insertion of the tracheal tube, number of intubation attempts to secure the airway, the need for adjuvant airway devices, hemodynamic changes, adverse events, and any airway-related trauma were recorded. MAIN RESULTS: The glottic view at the time of intubation did not differ significantly with the 2 devices; however, the C-MAC facilitated more rapid tracheal intubation compared with the FFS (P=.001). The peak heart rate response following insertion of the tracheal tube was also reduced (P=.004) in the C-MAC (vs FFS) group. CONCLUSION: The C-MAC may offer an advantage over the FFS with respect to the time required to obtain glottic view and successful placement of the tracheal tube in patients requiring cervical spine immobilization. PMID- 27185678 TI - Anesthesia care for subcutaneous implantable cardioverter/defibrillator placement: a single-center experience. AB - BACKGROUND: The recently approved subcutaneous implantable cardioverter/defibrillator (S-ICD) uses a single extrathoracic subcutaneous lead to treat life-threatening ventricular arrhythmias, such as ventricular tachycardia and ventricular fibrillation. This is different from conventional transvenous ICDs, which are typically implanted under sedation. Currently, there are no reports regarding the anesthetic management of patients undergoing S-ICD implantation. STUDY OBJECTIVES: This study describes the anesthetic management and outcomes in patients undergoing S-ICD implantation and defibrillation threshold (DFT) testing. METHODS: The study population consists of 73 patients who underwent S-ICD implantation. General anesthesia (n = 69, 95%) or conscious/deep sedation (n = 4, 5%) was used for device implantation. MEASUREMENTS: Systolic blood pressure (SBP) and heart rate were recorded periprocedurally for S-ICD implantation and DFTs. Major adverse events were SBP <90 mm Hg refractory to vasopressor agents, significant bradycardia (heart rate <45 beats per minute) requiring pharmacologic intervention and, "severe" pain at the lead tunneling site and the S-ICD generator insertion site based on patient perception. INTERVENTIONS: Of the 73 patients, 39 had SBP <90 mm Hg (53%), and intermittent boluses of vasopressors and inotropes were administered with recovery of SBP. In 2 patients, SBP did not respond, and the patients required vasopressor infusion in the intensive care unit. MAIN RESULTS: Although the S-ICD procedure involved extensive tunneling and a mean of 2.5 +/- 1.7 DFTs per patient, refractory hypotension was a major adverse event in only 2 patients. The mean baseline SBP was 132.5 +/- 22.0 mm Hg, and the mean minimum SBP during the procedure was 97.3 +/- 9.2 mm Hg (P < .01). There was also a mean 13-beats per minute decrease in heart rate (P < .01), but no pharmacologic intervention was required. Eight patients developed "severe" pain at the lead tunneling and generator insertion sites and were adequately managed with intravenous morphine. CONCLUSIONS: Among a heterogeneous population, anesthesiologists can safely manage patients undergoing S-ICD implantation and repeated DFTs without wide swings in SBP and with minimal intermittent pharmacologic support. PMID- 27185679 TI - Anesthetic management of an ex utero intrapartum treatment procedure: a novel balanced approach. AB - Ex utero intrapartum treatment (EXIT) procedures are therapeutic interventions for fetuses with life-threatening airway abnormalities and/or other prenatally diagnosed congenital malformations requiring immediate neonatal extracorporeal membrane oxygenation support. Although certain anesthetic goals are common among EXIT procedures, many different approaches to their management have been described in the literature. Herein, we present a novel anesthetic approach to an EXIT procedure for fetal micrognathia and retrognathia. We also review the indications and anesthetic considerations for these procedures and highlight the need for multidisciplinary collaboration to optimize clinical outcomes. PMID- 27185680 TI - Oral mask ventilation is more effective than face mask ventilation after nasal surgery. AB - OBJECTIVE: To evaluate and compare the face mask (FM) and oral mask (OM) ventilation techniques during anesthesia emergence regarding tidal volume, leak volume, and difficult mask ventilation (DMV) incidence. DESIGN: Prospective, randomized, crossover study. SETTING: Operating room, training and research hospital. SUBJECTS: American Society of Anesthesiologists physical status I and II adult patients scheduled for nasal surgery. INTERVENTIONS: Patients in group FM-OM received FM ventilation first, followed by OM ventilation, and patients in group OM-FM received OM ventilation first, followed by FM ventilation, with spontaneous ventilation after deep extubation. The FM ventilation was applied with the 1-handed EC-clamp technique. The OM was placed only over the mouth, and the 1-handed EC-clamp technique was used again. A child's size FM was used for the OM ventilation technique, the mask was rotated, and the inferior part of the mask was placed toward the nose. MEASUREMENTS: The leak volume (MVleak), mean airway pressure (Pmean), and expired tidal volume (TVe) were assessed with each mask technique for 3 consecutive breaths. A mask ventilation grade >=3 was considered DMV. MAIN RESULTS: DMV occurred more frequently during FM ventilation (75% with FM vs 8% with OM). In the FM-first sequence, the mean TVe was 249+/ 61mL with the FM and 455+/-35mL with the OM (P=.0001), whereas in the OM-first sequence, it was 276+/-81mL with the FM and 409+/-37mL with the OM (P=.0001). Regardless of the order used, the OM technique significantly decreased the MVleak and increased the TVe when compared to the FM technique. CONCLUSION: During anesthesia emergence after nasal surgery the OM may offer an effective ventilation method as it decreases the incidence of DMV and the gas leak around the mask and provides higher tidal volume delivery compared with FM ventilation. PMID- 27185681 TI - Comparison of three video laryngoscopy devices to direct laryngoscopy for intubating obese patients: a randomized controlled trial. AB - STUDY OBJECTIVE: To compare three different video laryngoscope devices (VL) to standard direct laryngoscopy (DL) for tracheal intubation of obese patients undergoing bariatric surgery. HYPOTHESIS: VL (vs DL) would reduce the time required to achieve successful tracheal intubation and improve the glottic view. DESIGN: Prospective, randomized and controlled. SETTING: Preoperative/operating rooms and postanesthesia care unit. PATIENTS: One hundred twenty-one obese patients (ASA physical status I-III), aged 18 to 80 years, body mass index (BMI) >30 kg/m(2) undergoing elective bariatric surgery. INTERVENTION: Patients were prospectively randomized assigned to one of 4 different airway devices for tracheal intubation: standard Macintosh (Mac) blade (DL); Video-Mac VL; Glide Scope VL; or McGrath VL. MEASUREMENTS: After performing a preoperative airway evaluation, patients underwent a standardized induction sequence. The glottic view was graded using the Cormack Lehane and percentage of glottic opening (POGO) scoring systems at the time of tracheal intubation. Times from the blade entering the patient's mouth to obtaining a glottic view, placement of the tracheal tube, and confirmation of an end-tidal CO2 waveform were recorded. In addition, intubation attempts, adjuvant airway devices, hemodynamic changes, adverse events, and any airway-related trauma were recorded. MAIN RESULTS: All three VL devices provided improved glottic views compared to standard DL (p < 0.05). Video Mac VL and McGrath also significantly reduced the time required to obtain the glottic view. Video-Mac VL significantly reduced the time required for successful placement of the tracheal tube (vs DL and the others VL device groups). The Video Mac and GlideScope required fewer intubation attempts (P< .05) and less frequent use of ancillary intubating devices compared to DL and the McGrath VL. CONCLUSION: Video-Mac and GlideScope required fewer intubation attempts than standard DL and the McGrath device. The Video-Mac also significantly reduced the time needed to secure the airway and improved the glottic view compared to standard DL. PMID- 27185683 TI - Incidence and risk factors for early postoperative reintubations. AB - STUDY OBJECTIVE: Reintubations are associated with significantly increased morbidity and mortality, increased hospital length of stay, and increased cost. Our aim was to assess the national incidence and associated risk factors for unanticipated early postoperative reintubations. DESIGN: Using the National Anesthesia Clinical Outcomes Registry (NACOR) from 2010 to 2014, multivariate logistic regression was fitted to determine if various patient, surgical, intraoperative, or provider data were associated with unanticipated early postoperative reintubations. SETTING: NACOR from 2010 to 2014. PATIENTS: A total of 2,970,904 cases were included. Multivariate analysis controlled for patient age, sex, and American Society of Anesthesiologists (ASA) Physical Status. INTERVENTIONS: None. MEASUREMENTS: We report odds ratios (ORs) and 95% confidence intervals (CIs) for the relative odds of an association of predictor variable with reintubations. MAIN RESULTS: The incidence of unanticipated early postoperative reintubations from the NACOR database was 0.061%. Overall, reintubations were more likely in the extremes of age (age under 1 year had OR = 3.46, 95% confidence interval [CI] = 2.64-4.52 and age 80+ has OR = 1.80, 95% CI = 1.50-2.15 when compared with age 19-49 years), patients with ASA Physical Status 3 and 4 (OR = 4.06, 95% CI = 3.38-4.86 and OR = 8.65, 95% CI = 7.11-10.52, respectively, when compared with ASA 1), longer case duration (180-360 minutes OR = 13.87, 95% CI = 10.7-17.98 when compared with cases less than 60 minute duration), and cases that had a resident trainee present (OR = 1.22, 95% CI = 1.03-1.44 when compared with no resident present). Thoracic and vascular surgical procedures had the highest rates of reintubation when compared with general surgery (OR = 3.47, 95% CI = 2.81-4.28 and OR = 1.51, 95% CI = 1.24-1.82, respectively). CONCLUSIONS: A number of risk factors correlate with an increased risk of unanticipated early postoperative reintubations, including extremes of age, patients with greater medical comorbidities, longer operations, and patients undergoing thoracic procedures. PMID- 27185682 TI - Benefit of sugammadex on lung ventilation evaluated with electrical impedance tomography in a morbidly obese patient undergoing bariatric surgery. PMID- 27185684 TI - The comparison of insertion depth for orotracheal intubation between standard polyvinyl chloride tracheal tubes and straight reinforced tracheal tubes. AB - STUDY OBJECTIVE: To investigate whether these properties of reinforced tubes cause difference in insertion depth compared to standard polyvinyl chloride tracheal tubes. DESIGN: A randomized controlled trial. SETTING: Operation room. MATERIALS: Standard polyvinyl chloride tracheal tubes, reinforced tubes. INTERVENTIONS: Seventy-six adult patients undergoing surgery under general anesthesia were randomly allocated with standard tube (n=38) or reinforced tube (n=38) intubation. The endotracheal tube was fixed at the right canine with a predetermined insertion depth using the formula: endotracheal tube insertion length (cm)=0.1977 * [body height (cm)] - 12.7423. MEASUREMENTS: The distances between the tracheal tube tip and the carina using fiberoptic bronchoscope. MAIN RESULTS: The mean tip-to-carina distance of reinforced tube was about 1.2cm longer than that of standard tube (P<.001). CONCLUSIONS: The insertion depth of straight reinforced tracheal tubes can be shorter than that of standard polyvinyl chloride tracheal tubes due to different tube pathways in the upper airway. PMID- 27185685 TI - Prone position results in enhanced pressor response to ephedrine compared with supine position during general anesthesia. AB - STUDY OBJECTIVE: To elucidate and compare the pressor response to ephedrine in the prone or supine position during general anesthesia (GA). DESIGN: Prospective cohort study. SETTING: Department of General Surgery or Spine Surgery, Zhongda Hospital, Southeast University, Nanjing, China. PATIENTS: Fifty-six patients who were scheduled to undergo elective surgery in the supine or prone position (n = 28 each) and using a generic GA protocol. INTERVENTIONS: During surgery, the patients received intravenous (IV) ephedrine when their systolic blood pressure (SBP) decreased to 90 to 110 mm Hg. MEASUREMENTS: Hemodynamic changes were measured at 1-minute intervals for 10 minutes and were compared with baseline. MAIN RESULTS: Forty-nine patients (23 in the prone position and 26 in the supine position) completed the study. There were no significant differences between the groups with regard to demographic characteristics, hemodynamic parameters, end tidal concentration of sevoflurane, and dose of propofol and remifentanil (all P> .05). After the bolus injection of ephedrine, a significant increase in SBP was observed in both groups compared to baseline, but the duration and magnitude of the increase in SBP were longer and greater in the prone position than in the supine position. The magnitude of increase of the mean blood pressure was significantly greater in the prone position compared to the supine position at 2 to 7 minutes after ephedrine injection. Ephedrine could cause significant increase in diastolic blood pressure 2 minutes after IV injection, which could last until at least 9 minutes in the prone position group compared to only for 5 minutes in the supine position group (all P< .05). CONCLUSION: Compared to the supine position, the prone position could augment the pressor response to IV ephedrine during GA. Further studies are recommended to identify its association with other confounding factors such as surgery type or duration, patient history of cardiovascular disease, or patient hydration status. PMID- 27185686 TI - Flow rates through intravenous access devices: an in vitro study. AB - STUDY OBJECTIVE: Fluid administration using intravenous (IV) access devices is required in many settings. There are a lack of quantitative data comparing traditional cannulas and modern access devices. We aimed to investigate flow rates through modern intravenous access devices using an in vitro system. DESIGN: This is an experimental study. SETTING AND MEASUREMENTS: Rates of flow of intravenous fluids (crystalloid and colloid) were measured through various access devices using a uroflowmeter. Standardized conditions and repeat measurements ensured validity. Fluid was administered with or without the addition of a pressure bag and needle-free valve. MAIN RESULTS: Increasing the size of cannulas improved flow. Fourteen-gauge cannulas had significantly higher mean flow rates compared to 14G central venous lines in all conditions (136% higher with no pressure bag/valve; 95% CI, +130% to +152%; P < .001). Both the emergency infusion device and rapid infusion catheter produced significantly increased mean flows compared to a 14G cannula (12% higher for emergency infusion catheter; 95% CI, +7% to +15%; P = .008, and 15% higher for rapid infusion catheter; 95% CI, +12% to +21%; P = .004). The needle-free valve significantly impaired flow on 16G and wider IV access devices (36% lower with no pressure bag using 14G cannula; 95% CI, -29% to -46%; P = .003), but flow reductions in narrower IV access were insignificant. Pressure bags significantly improved flow in all devices, in all combinations. CONCLUSIONS: Flow rates in IV devices can be maximized by pressure bag use and removal of needle-free valves. The rapid infusion catheter and emergency infusion catheter allow some increase in flow over a 14G cannula. Familiarity with varying flow rates across IV access devices could better inform clinical decisions. PMID- 27185687 TI - Estimating the number of difficult airway carts needed in an operating suite: Resource planning without compromising patient safety. AB - STUDY OBJECTIVE: To determine the number of difficult airway (DA) carts required based on the number of anesthetising locations and patients risk of DA. DESIGN: Binomial distributions. SETTING AND PATIENTS: Various hypothetical settings and patient cohorts. INTERVENTIONS AND MEASUREMENTS: Binomial distributions were used to calculate the number of distinct combinations of DAs by number of anesthetising locations assuming an average risk of 10%. The 'at least' number of DAs was calculated using cumulative probabilities of having exactly two plus more than 2 DAs up to the total number of simultaneously started anesthetising locations or until the cumulative probability exceeds the 50% threshold, therefore being more likely than not. MAIN RESULTS: The probability of encountering concurrent DAs increases as the number of simultaneously started anesthetising locations increases. For at least 2 concurrent DAs, the probability first exceeds 50% at 17 locations. The corresponding thresholds for at least 3 and 4 concurrent DAs, are 27 and 37 locations respectively. The probability of at least 2 concurrent DAs will exceed 50% when approximately 17 anesthetising sites are started simultaneously and a 10% worst case risk is assumed. CONCLUSIONS: With continuing resource constraints, proper planning of human and capital resources for DAs needs to be addressed without compromising patient safety. It is recommended that every block of 15-20 sites be equipped with a DA cart, that anaesthesia groups develop and rehearse DA algorithms with available equipment, and that preoperative anaesthesia clinics be used to identify DA therefore providing logistical leverage. PMID- 27185688 TI - Another cause of damage to tracheal tube cuff during nasotracheal intubation. PMID- 27185689 TI - Ventilation failure due to recanalization of a tracheostomy orifice during the induction of anesthesia. PMID- 27185690 TI - Pneumothorax after tracheostomy closure with successful nonsurgical management. AB - A 3-year-old girl presented for routine closure of her tracheostomy site. She was intubated easily for the procedure, and the wound was closed with a drain in place. In recovery, the mother noticed fullness in the patient's submandibular region, and on examination, the girl had subcutaneous emphysema in the neck bilaterally. She returned to the operating room for exploration, and air was released from the surgical site. The wound was again closed with a drain in place, and the patient was extubated uneventfully. After arriving to the pediatric intensive care unit for monitoring, the patient acutely developed respiratory distress and was found to have pneumomediastinum and pneumothorax and was emergently intubated. She was observed closely, and the following day, the pneumothorax improved, and she successfully extubated without further complication. PMID- 27185691 TI - Transversus abdominal plane and rectus sheath block combination for intractable anterior cutaneous nerve entrapment syndrome after severe cholecystitis. PMID- 27185692 TI - Postoperative extradural hematoma of the cervical spine: a rare but avoidable complication. PMID- 27185693 TI - A liquid crystal display monitor failure of a McGRATH video laryngoscope. PMID- 27185694 TI - Intrinsic positive end-expiratory pressure during ventilation through small endotracheal tubes during general anesthesia: incidence, mechanism, and predictive factors. AB - STUDY OBJECTIVE: To assess the safety of mechanical ventilation and effectiveness of extrinsic positive end-expiratory pressure (PEEP) (PEEPe) in improving peripheral oxygen saturation (SpO2) during direct microlaryngeal laser surgery; to assess the incidence, amount, and nature (dynamic hyperinflation or airflow obstruction) of ensuing intrinsic PEEP (PEEPi); and to find a surrogate PEEPi indicator. DESIGN: Quasiexperimental. SETTING: S. Raffaele Hospital (Milano), November 2009 to December 2010. PATIENTS: Fifty-two adults scheduled for direct microlaryngeal laser surgery. Exclusion criterion is pregnancy. INTERVENTIONS: Twenty-one percent O2 mechanical ventilation through 4.5- to 5.5-mm internal diameter endotracheal tubes; in 29 patients, after measurement of PEEPi, an identical amount of PEEPe was added; and PEEPi. MEASUREMENTS: SpO2, peak (Pawpeak) and plateau (Pawplateau) airway pressure, and end-expiratory carbon dioxide were measured every 5 minutes. Respiratory compliance (Crs) was computed. PEEPi was measured (end-expiratory occlusion method). MAIN RESULTS: PEEPi >=5 cm H2O occurred in 14 patients (27%) after intubation, in 16 (30%) at the beginning, and in 14 (27.3%) at the end of surgery. Thirty-one patients (59.4%) exhibited PEEPi >=5 cm H2O on at least 1 time point. PEEPi at the beginning of surgery was positively correlated with Pawplateau, Crs, tidal volume, and body mass index. Body mass index was the only predictor for the occurrence of PEEPi >=5 cm H2O. At the beginning of surgery, the Pawplateau receiver operating characteristic curve predicting PEEPi >=5 cm H2O had area under the receiver operating characteristic curve of 0.85; best cutoff value of 15.5 cm H2O (sensitivity, 88.9%; specificity, 75%; correctly classified cases, 86.1%). When PEEPe was applied, in 23 cases (82.1%), total PEEP equaled PEEPe+ PEEPi; in 3 (10.7%), it was lower; and in 2 (7.1%), it was higher. Application of PEEPe increased SpO2 (P< .05) and Crs (P< .05). CONCLUSIONS: During ventilation through small endotracheal tubes, PEEPi (mostly due to dynamic hyperinflation) is common. Hemodynamic complications, barotrauma, and O2 desaturation (reversible with PEEPe) are rare. Pawplateau provided by ventilators is useful in suspecting and monitoring the occurrence of PEEPi and allows detection of lung overdistension as PEEPe is applied. PMID- 27185695 TI - Reliability of a faculty evaluated scoring system for anesthesiology resident applicants (Original Investigation). AB - STUDY OBJECTIVE: To assess reliability and reproducibility of a recently instituted anesthesiology resident applicant interview scoring system at our own institution. DESIGN: Retrospective evaluation of 2 years of interview data with a newly implemented scoring system using randomly assigned interviewing faculty. SETTING: Interview scoring evaluations were completed as standard practice in a large academic anesthesiology department. SUBJECTS: All anesthesiology resident applicants interviewed over the 2013/14 and 2014/15 seasons by a stable cohort of faculty interviewers. Data collection blinded for both interviewers and interviewees. INTERVENTIONS: None for purposes of study - collation of blinded data already used as standard practice during interview process and analysis. MEASUREMENTS: None specific to study. MAIN RESULTS: Good inter-rater faculty reliability of interview scoring (day-of) and excellent inter-faculty reliability of application review (pre-interview). CONCLUSIONS: Development of a department specific interview scoring system including many elements beyond traditional standardized tests shows good-excellent reliability of faculty scoring of both the interview itself (including non-technical skills) and the application resume. PMID- 27185696 TI - A comparison of the I-Gel supraglottic device with endotracheal intubation for bronchoscopic lung volume reduction coil treatment. AB - STUDY OBJECTIVE: To compare the use of the I-gel airway with orotracheal intubation (OTI) for bronchoscopic lung volume reduction (BLVR) coil treatment in patients with severe chronic obstructive pulmonary disease (COPD) with heterogeneous emphysema, since it has been proved that supraglottic airways have lower incidence of postoperative respiratory complaints compared to OTI. DESIGN: A comparative, prospective observational study was designed to assess the use of the I-gel airway compared with the OTI. SETTING: Bronchoscopy room at the University Hospital Fundacion Jimenez Diaz, Madrid. Tertiary care center. PATIENTS: Thirty-three procedures were carried out in 22 patients diagnosed with COPD with severe heterogeneous emphysema undergoing BLVR coil treatment under general anaesthesia. INTERVENTION: Seventeen procedures were carried out with I gel and 16 with endotracheal tube. Airway device choice was left to the attendant anesthesiologist. MEASUREMENTS: Tidal volume, peak pressure, and the presence of gas leaks were compared. Adverse events during the procedure and within the first 3 hours later were also recorded. MAIN RESULTS: Ventilation parameters obtained showed no significant differences. Mean tidal volume was 466.6 +/- 28.2 mL and 478.7 +/- 34.0 mL (P > .05), mean peak pressure was 17.9 +/- 2.5 cmH2O and 19.4 +/- 2.4 cmH2O (P > .05) and mean gas leaks was 71 +/- 17.6 mL and 79 +/- 15.5 mL (P > .05) for I-gel group (IgelG) and endotracheal tube group respectively. No serious complications were reported. One case of pneumothorax was reported in the endotracheal tube group, which was resolved with a chest drainage tube without further complications. CONCLUSION: The I-gel airway ensures appropriate ventilation and makes the use of the flexible fiberoptic bronchoscope quite easy. Therefore, we consider that the I-gel device is an effective and safe alternative to classical OTI for airway management in COPD patients with severe heterogeneous emphysema undergoing BLVR coil treatment. PMID- 27185697 TI - Hemiparesis after general anesthesia in a patient with migraine with unilateral motor symptoms. AB - DESIGN: This is a case report. SETTING: The setting is at a postoperative recovery area. PATIENTS: A 52-year-old woman with a history of migraine with unilateral motor symptoms developed hemiparesis after undergoing general anesthesia for total thyroidectomy. INTERVENTIONS: No interventions were performed. MEASUREMENTS/MAIN RESULTS: Head computed tomography and magnetic resonance imaging were normal. Laboratory studies including basic metabolic panel and complete blood count were also within normal limits. CONCLUSIONS: General anesthesia may be a trigger for hemiplegic migraine syndromes; however, it behooves the practitioner to rule out acute neurologic and metabolic events before making this diagnosis. PMID- 27185698 TI - Patient preference for the pre-anesthesia evaluation: Telephone versus in-office assessment. AB - STUDY OBJECTIVE: Pre-anesthesia evaluation (PAE) is designed to reduce patient and family anxiety, identify pre-existing health issues, avoid surgical delays, minimize costs, and tailor an anesthetic plan. If PAE requires a clinic visit, patients must take time off work and may incur travel and childcare costs. A telephone-based Preoperative Assessment Clinic can minimize patient inconvenience, while maintaining high-quality patient care and improving efficiency. We assessed patient satisfaction with a telephone PAE and determined whether patients preferred a telephone PAE or a conventional clinic visit. DESIGN: Prospective, institutional review board-approved study. SETTING: University hospital. PATIENTS: We conducted an IRB-approved telephone survey of 75 adult, post-operative patients. INTERVENTIONS: Telephone survey. MEASUREMENTS: Patients were asked about their preference for a telephone PAE over an in-person evaluation. Survey questions included assessment of patient satisfaction with their anesthesia evaluation, operation, and anesthetic delivered. Delays and day of surgery cancellations were reviewed. MAIN RESULTS: The majority (97%) of patients stated they preferred a telephone PAE. Patient satisfaction was unaffected by driving distance (30+/-54 mi), ASA physical status or duration of surgery (169+/-159 min). Even patients who were not satisfied with their anesthetic (N=5) still preferred the telephone-based PAE. No increase in surgical delays or cancellation was noted. CONCLUSION: The majority of patients in this survey preferred a telephone PAE. Given the large catchment area of our hospital of nine counties, telephone-based interviews add to patient convenience and likely increase compliance with the PAE. Even patients who live in close proximity to our hospital (<5 mi) preferred a telephone assessment. A telephone based PAE provides high patient satisfaction over a traditional office visit while increasing patient convenience. Larger studies are necessary to ensure that telephone PAEs compare well with in-person examinations. PMID- 27185699 TI - A randomized placebo-controlled study of preoperative pregabalin for postoperative analgesia in patients with spinal surgery. AB - STUDY OBJECTIVE: To determine whether single preoperative administration of 2 different doses of pregabalin (75 and 150 mg) could decrease postoperative pain intensity and opioid consumption following posterior lumbar interbody fusion surgery. DESIGN: Prospective, randomized, active placebo-controlled, double blinded study. SETTING: Postoperative recovery area and patients' room. PATIENTS: Ninety-seven adult, American Society of Anesthesiologists physical status 1 and 2 patients. INTERVENTIONS: Patients were randomly assigned to receive diazepam 5 mg as an active placebo (D5), pregabalin 75 mg (P75), or pregabalin 150 mg (P150). The study drug was orally administered 2 hours prior to surgery and a standard anesthetic technique was used. Postoperative pain was managed using intravenous patient-controlled analgesia with morphine. MEASUREMENT: The visual analog scale at rest was used to measure pain intensity immediately after extubation at the postanesthesia care unit, and then 2, 4, 6, 12, 18, 24, 36, and 48 hours after surgery. Morphine consumption and adverse effects were assessed until 48 hours after surgery. MAIN RESULTS: The visual analog scale score at rest was lower in the P150 group than in the D5 group until 2 hours after surgery. Morphine consumption was lower in the P150 group than in the D5 from 0 to 12 hours after surgery. CONCLUSIONS: Single preoperative administration of 150 mg of pregabalin 2 hours prior to surgery reduced postoperative pain intensity and morphine consumption compared with 5 mg diazepam in patients who underwent posterior lumbar interbody fusion. PMID- 27185700 TI - Major complications of regional anesthesia in 11 teaching hospitals of China: a prospective survey of 106,569 cases. AB - STUDY OBJECTIVE: To determine the incidence of major complications in patients undergoing regional anesthesia (RA) in China. DESIGN: Multicenter prospective survey. SETTING: Eleven teaching hospitals in China. PATIENTS AND INTERVENTIONS: A total of 106,569 patients undergoing RA from April 1, 2009, to April 30, 2011, were involved. MEASUREMENT: Information on patients, types of surgery, and RA techniques was collected with a standardized chart. After RA, the patients were followed up by an investigator in each center for 1 to 3 weeks according to the patient's condition. Data were integrated and analyzed with a structured query language server system. MAIN RESULTS: Among the patients undergoing RA, 37 developed major complications, including Horner syndrome (n = 9; 0.84/10,000), recurrent laryngeal nerve blockade (n = 6; 0.56/10,000), cardiac arrest (n = 1; 0.09/10,000), hematoma (n = 2; 0.19/10,000), seizures (n = 5; 0.46/10,000), catheter break (n = 1; 0.09/10,000), paraplegia (n = 1; 0.09/10,000), cauda equina syndrome (n = 2; 0.19/10,000), and extensive neuraxial block (n = 10; 0.94/10,000). The incidence of major RA complications varied from 0.8/10,000 to 18.8/10,000 among centers and was highest in cervical plexum block. Plastic surgery had the highest incidence of complications (19.0/10,000), most of which were recurrent extensive neuraxial block. The total incidence of major RA complications was 3.47/10,000. CONCLUSION: This large, multicenter, prospective survey revealed the incidence of major complications after RA in China's hospitals. Although severe complication like cardiac arrest is rare, it is distressing and challenging. Hence, there is still a room to improve on daily basis to further reduce complications related to RA. PMID- 27185701 TI - Comparative efficacy of stellate ganglion block with bupivacaine vs pulsed radiofrequency in a patient with refractory ventricular arrhythmias. AB - There is increasing interest in interventional therapies targeting the cardiac sympathetic nervous system to suppress ventricular arrhythmias. In this case report, we describe an 80-year-old patient with ischemic cardiomyopathy and multiple implantable cardioverter-defibrillator shocks due to refractory ventricular tachycardia and ventricular fibrillation who was unable to continue biweekly stellate ganglion block procedures using bupivacaine 0.25% for suppression of his arrhythmias. He had previously failed antiarrhythmic drug therapy with amiodarone, catheter ablation, and attempted surgical autonomic denervation. He underwent pulsed radiofrequency treatment (3 lesions, 2 minutes each, temperature 42 degrees C, 2-Hz frequency, 20-millisecond pulse width) of the left stellate ganglion resulting in persistent arrhythmia suppression for more than 12 months duration. This represents the first report of a pulsed radiofrequency stellate ganglion lesion providing long-term suppression of ventricular arrhythmias. Further study of this technique in patients with refractory ventricular tachycardia or ventricular fibrillation is warranted. PMID- 27185702 TI - Two methods for teaching basic upper airway sonography. AB - STUDY OBJECTIVE: The purpose of this study was to evaluate and compare hands-on gel phantom versus instructional video teaching methods to improve anesthesia residents and staff members' ability to correctly identify airway structures using ultrasound on a human volunteer. DESIGN: Randomized, controlled trial. SETTING: Simulation laboratory. STUDY SUBJECTS: Fifty-four anesthesiology resident and staff members (27 anesthesiologists and 27 anesthesiology residents) at the University of Wisconsin-Madison. INTERVENTIONS: Study subjects were randomized into one of three groups: control (standard medical knowledge), video training, or gel phantom training. After providing study instructions and training (if relevant), study subjects were asked to perform sonoanatomy identification of the thyroid cartilage, cricoid cartilage, cricothyroid membrane, and the tracheal rings in both the transverse and longitudinal views. Study subjects then returned 14 to 24 days following initial assessment for evaluation of skills retention. They were again instructed to identify the same airway structures as during the initial assessment with scoring performed by the same assessor. MAIN RESULTS: All group characteristics were similar at baseline and follow-up. Both training tools produced a learning effect at baseline and follow-up compared to standard anesthesia training. No differences in overall airway structure identification success between groups receiving video versus gel airway phantom training were observed. CONCLUSIONS: Use of either a low cost, airway gel phantom training model for hands-on training or a simple instructional teaching video can be used in a single training session to improve staff anesthesiologist and anesthesia resident knowledge and skills for ultrasound identification of upper airway anatomy. PMID- 27185703 TI - Potential mechanism of arytenoid dislocation following insertion of a calibrating orogastric tube. PMID- 27185704 TI - A peer-designed selective in anesthesiology, critical care, and perioperative medicine for first- and second-year medical students. AB - STUDY OBJECTIVE: The objective of this study was to design and implement a preclinical elective (termed selective) in anesthesiology, critical care, and perioperative medicine and to report survey results assessing the impact of the selective on first- and second-year medical students' understanding of basic concepts, comfort with procedural skills, and interest in the specialty. DESIGN: Preinvention and postintervention survey evaluation was used as the design of this study. SETTING: The study was conducted at Mayo Medical School and Mayo Clinic. PARTICIPANTS: The participants in this study are first- and second-year medical students. INTERVENTIONS: A 1-week introductory anesthesiology curriculum was developed to include didactic sessions, shadowing experiences, lunch and dinner panels, mentorship and networking opportunities, and procedural workshops in airway management, ultrasound, and vascular access techniques. MEASUREMENTS: Preselective and postselective surveys using a 10-point scale (1, strongly disagree; 10, strongly agree) were administered 1 week before and after the selective. MAIN RESULTS: A total of 8 students participated in the selective, with a 100% survey response rate. Students reported significant increases for all survey questions regarding basic concepts and skills. The largest increases were reported in comfort with airway management skills, understanding of the perioperative surgical home model, and vascular access skills. All participants indicated a higher likelihood of pursuing anesthesiology as a career and attributed their increased interest in anesthesiology to the selective. CONCLUSIONS: This new selective was successful in giving first- and second-year medical students a comprehensive overview of anesthesiology and increasing medical student interest in the specialty. The success of this selective leads to promising belief that similar peer-designed educational experiences can be developed at other medical schools to improve education and interest in this area of medicine. PMID- 27185705 TI - Transversus abdominis plane block as the primary anesthetic for peritoneal dialysis catheter surgery. AB - STUDY OBJECTIVE: The primary goal of this study was to determine whether transversus abdominis plane (TAP) blocks were effective as the primary anesthetic technique for insertion and/or removal of peritoneal dialysis catheters. DESIGN: This study is a descriptive case series investigation. SETTING: Operating rooms at a tertiary care academic medical center. PATIENTS: Twenty-four patients, American Society of Anesthesiologists (ASA) physical status 3 and 4, were included in this study. INTERVENTIONS: Patients who had received a TAP block preoperatively for open surgical insertion or removal of a peritoneal dialysis catheter over a 26-month period with the intent of the block to serve as the primary anesthetic were included in this study. MEASUREMENTS: Preoperative and intraoperative sedative medications and local anesthetic medications were analyzed. The primary outcome of the study was the ability of the TAP block to provide surgical anesthesia as determined by a lack of need to convert to general anesthesia (defined by placement of an airway device, use of volatile anesthetics, intraoperative propofol infusion dose equal to or greater than 100 MUg kg(-1) min(-1)). Secondary outcomes included analysis of any complications from the higher concentrations of local anesthetics required for surgical block. MANI RESULTS: Of 24 patients, 21 underwent the procedure without conversion to general anesthesia as defined above. No complications related to local anesthetics were found. CONCLUSION: Transversus abdominis plane blockade can be successful at serving as the primary anesthetic modality for the insertion and/or removal of a peritoneal dialysis catheter by open-surgical approach. There were no systemic toxic effects or other complications recorded. PMID- 27185706 TI - Airway protection using a modified nasopharyngeal tube after orthognathic surgery. PMID- 27185707 TI - A universal Echosupport can fix a technique of ultrasound-guided continuous femoral nerve block. PMID- 27185708 TI - Perforation of the superior vena cava 5 days after insertion of a central venous catheter through the left internal jugular vein. AB - We describe a very rare case of an indwelling central venous catheter (CVC) through the left internal jugular vein that perforated the superior vena cava (SVC) wall postoperatively, although the CVC was placed in the appropriate position preoperatively. Three days after CVC insertion, a chest radiograph showed that the CVC tip had moved from the lower SVC to the upper SVC. Five days after the insertion, computed tomography showed SVC perforation and the resulting hydrothorax. In cases of CVC insertion through the left side, the CVC tip should not be placed in the upper SVC (zone B). Considering individual clinical factors and the indwelling period for the CVC, the left innominate vein (zone C) may be a suitable site for the left-sided CVC tip to reduce the risk of SVC perforation. PMID- 27185710 TI - Pectoral nerves block for a contraction of the latissimus dorsi muscle. PMID- 27185709 TI - Multiple anesthetics for a patient with stiff-person syndrome. AB - Stiff-person syndrome is a progressive disease of muscle rigidity and spasticity due to a deficiency in the production of gamma-aminobutyric acid. Because of the rarity of the condition, little is known about effects of anesthesia on patients with stiff-person syndrome. This report describes the clinical course for a single patient with stiff-person syndrome who received general anesthesia on 3 separate occasions. Her anesthetics included use of both neuromuscular blockade and volatile agents. Unlike several previous reports regarding anesthesia and stiff-person syndrome, the postoperative period for this patient did not require prolonged intubation or result in any residual weakness. PMID- 27185711 TI - Need for a new evaluation scale for the efficacy of ventilation with supraglottic devices. PMID- 27185712 TI - The use of inhaled sevoflurane during operative hysteroscopy is associated with increased glycine absorption compared to intravenous propofol for maintenance of anesthesia. AB - STUDY OBJECTIVE: To compare the effects of anesthesia maintenance drugs (inhaled sevoflurane versus intravenous propofol) used in general anesthesia on the absorption of glycine 1.5% solution during hysteroscopy. DESIGN: Prospective comparative study. SETTING: Tertiary care university hospital. PATIENTS: One hundred fifteen women undergoing hysteroscopy. INTERVENTIONS: Women were assigned to receive general anesthesia with inhaled sevoflurane (n = 77) or intravenous propofol (n = 38) to maintain anesthesia. MEASUREMENTS: The primary endpoint was clinically relevant glycine 1.5% absorption (>1000 mL), while secondary endpoints were the median of glycine absorption, operative time, complications and the incidence of discontinuation of the hysteroscopic procedure due to excessive glycine 1.5% absorption. MAIN RESULTS: Maintenance with sevoflurane produced significantly increased absorption of glycine 1.5% solution compared to intravenous anesthesia (264 vs 202 mL, P = .007). Clinically relevant absorption rates (>1000 mL) were observed in the sevoflurane group (P = .04) while none of the women receiving intravenous anesthesia reached this absorption level. No cases of severe post-operative hyponatremia (Na(1+)<125 mmol/L) or adverse events derived from glycine 1.5% absorption were reported. No major complications (such as perforations, severe hemorrhage or infection) were presented during the interventions. CONCLUSIONS: The results of the present study show that the use of inhaled sevoflurane is associated with significantly increased glycine 1.5% absorption compared to intravenous propofol for the maintenance of anesthesia. However, further randomized controlled trials are needed to assess the possible mechanisms and risk factors involved in the higher absorption induced by sevoflurane. PMID- 27185713 TI - Dexmedetomidine suppresses intractable hiccup during anesthesia for cochlear implantation. AB - We report on the successful use of dexmedetomidine to treat persistent intractable hiccup in a child who underwent cochlear implantation under sevoflurane-fentanyl anesthesia. PMID- 27185714 TI - A rare combination of undiagnosed hypertrophic cardiomyopathy revealed by intraoperative anaphylaxis resulting in acute left ventricular outflow obstruction and cardiac arrest. AB - A 75-year-old female presented for left total hip reimplantation and suffered pulseless electrical activity arrest upon lateral positioning and administering vancomycin. Resuscitation was achieved according to Advanced Cardiac Life Support protocol. Post-event echocardiography showed hypertrophic cardiomyopathy with asymmetrical septal thickening, an under-filled left ventricle, dynamic left ventricular outflow obstruction, and severe mitral regurgitation related to systolic anterior motion of the mitral valve. Laboratory analysis showed a tryptase level of 209 ng/mL. After multispecialty evaluation, it was concluded that the patient's arrest was due to vancomycin anaphylaxis in the setting of previously undiagnosed hypertrophic cardiomyopathy leading to acute left ventricular outflow tract obstruction. After medical optimization of the patient's cardiomyopathy and an evaluation of potential intraoperative allergic triggers, the patient underwent a successful hip reimplantation without incident. This case presents a novel combination of events leading to intraoperative cardiac arrest. Rapid identification and an understanding of the cause(s) of cardiac arrest in this setting are critical for effective perioperative care. PMID- 27185716 TI - Electroconvulsive therapy for depression following acute coronary syndromes: a concern for the anesthesiologist. AB - The prevalence of depression in patients with cardiovascular disease is higher than general population and especially following an acute coronary syndrome (ACS), a significant number of patients report a wide spectrum of behavioral and mood changes attributable to clinical depression. Treatment of depression following ACS event is particularly challenging since most of the therapeutic modalities are associated with increasing the systemic sympathetic tone from neurogenic or pharmacologic sources. Increased activity of the adrenergic and catecholamine activity may further deter the myocardial oxygen supply and demand therefore treating depression should be carefully evaluated for its risk benefit ratio. Electroconvulsive therapy (ECT) is recommended for patients with severe depression, in whom behavioral and pharmacologic treatments have failed. Patients who refuse to take medications or present with any psychological emergency such as harming self or others, are also candidates for ECT. ECT is also associated with sudden surges of catecholamines and may cause recurrent myocardial ischemia and fatal dysrhythmias in patients convalescing from an ACS event. Herein, we provide an overview and practical guidelines for management of patients presented for ECT following ACS. PMID- 27185715 TI - The Easytube for airway management: a systematic review of clinical and simulation studies. AB - STUDY OBJECTIVE: Endotracheal intubation is considered the criterion-standard technique for securing the airway. Supraglottic airway devices (SADs) represent a major advance in airway management and are recommended by the guidelines in difficult situations such as Advanced Life Support and "cannot ventilate-cannot intubate" scenarios. The Easytube (EzT) is an SAD introduced a decade ago but not included yet in the above guidelines. DESIGN: Systematic review of MEDLINE and EMBASE according to PRISMA guidelines available up to January 12, 2016. SETTING: We collected experimental and clinical evidence regarding EzT positioning performed by medial students, anesthesiologists, paramedics, or nurses. PATIENTS: Manikins, cadavers, or patients. INTERVENTIONS: EzT positioning in both clinical and simulation studies, both under standard and under difficult scenarios. MEASUREMENTS: Time to insertion and time to ventilation, success rate and operator's assessment of the device, change in ventilatory parameters, and major complications. MAIN RESULTS: Fifteen manuscripts were found: 6 prospective clinical studies and 9 conducted under experimental conditions (7 with a simulator and 2 on cadavers). The EzT inserted by both inexperienced and experienced personnel in most studies had high success rate, and it showed excellent results also during simulated cardiopulmonary resuscitation and in difficult airway scenarios. The EzT had better ventilatory parameters as compared with the Combitube and showed great airway sealing capacity, comparable to the Combitube and to the laryngeal mask airway and superior to other SADs. EzT allowed the insertion of large nasogastric tubes and has only mild adverse effects like other SADs. No major complications were described. CONCLUSION: The EzT appears to be a safe and a good alternative to established SADs. It may be considered among SADs by future guidelines on Advanced Life Support and "cannot ventilate-cannot intubate" scenarios. PMID- 27185717 TI - Use of a videolaryngoscope with a tube guide for metal stent placement to subglottic tracheal tumor. PMID- 27185718 TI - Do mask aperture bars of extraglottic airway devices prevent prolapse of epiglottis causing airway obstruction? A randomized crossover trial in anesthetized adult patients. AB - STUDY OBJECTIVE: The study objective is to determine whether extraglottic airway devices (EADs) with or without mask aperture bars (MABs) result in similar anatomical positions in patients undergoing surgery. DESIGN: Prospective, randomized, crossover comparison of four extraglottic airway devices. SETTING: Operating theatre at a large teaching hospital. PATIENTS: Eighty consenting patients scheduled to undergo surgery with general anesthesia. INTERVENTIONS: Patients were randomly allocated to receive anesthesia with one of four tested EADs. Two versions of each EAD were inserted in random order; one with and one without MABs. MEASUREMENTS AND MAIN RESULTS: Endoscopic evaluation did not demonstrate any difference between the EADs with or without MABs. Contact between MABs and arytenoids (n=15) and herniation of arytenoids (n=7) was restricted to the Cobra-group patients. In nine patients the epiglottis made contact with a MAB, although this contact was very limited and often unilateral. CONCLUSION: This study demonstrated that the anatomical position of the four tested single use EADs is similar with or without mask aperture bars. We therefore question whether MABs have a protective role in prevention of airway occlusion and whether MABs are essential components. In the overall majority of EADs with MABs, the latter did not prevent contact with the epiglottis. Contact and herniation of the laryngeal structures are seen more frequently when more than two MABs are present. PMID- 27185719 TI - National incidences and predictors of inefficiencies in perioperative care. AB - STUDY OBJECTIVE: The operating room suite can be one of the most costly units within the hospital. Some of these costs stem from postoperative unplanned admissions, case cancellations, case delays, and extended recovery room times. The objective is to determine the clinical predictors of these operating room inefficiencies. DESIGN: Retrospective data analysis. SETTING: Operating room, postoperative recovery area. PATIENTS: Surgical patients whose perioperative data were reported to the Anesthesia Quality Institute's National Anesthesia Clinical Outcomes Registry from 2010 to 2015. INTERVENTIONS: We identified all cases that reported unplanned admissions, case cancellations, case delays, and extended recovery room times. MEASUREMENTS: Patient demographics, intraoperative characteristics, and provider information were collected for each case. Univariate and multivariate logistic regressions were fitted to determine if these various characteristics were associated with the outcomes of interest. MAIN RESULTS: The incidence of unplanned admissions (0.18%), case cancellations (0.05%), extended recovery room stays (1.12%), and case delays (14.43%) were reported. A positive predictor for unplanned admissions included elderly patients (odds ratio [OR], 1.34; 95% confidence interval [CI], 1.16-1.48), whereas cases not performed under general anesthesia had lower rates (P<.001). For case cancellations, higher American Society of Anesthesiologists classes had the highest risk (OR, 2.17; 95% CI, 1.81-2.60). Longer cases and elderly patients are the main predictors for extended postanesthetic care unit stays among all surgeries (OR, 1.54; 95% CI, 1.47-1.62; OR, 1.42; 95% CI, 1.34-1.50, respectively). Pediatric patients and monitored anesthetic care cases had highest odds for case delays (OR, 3.02; 95% CI, 2.93-3.11; OR, 4.98; 95% CI, 4.88-5.07, respectively). CONCLUSIONS: This study reports the national incidence and various clinical predictors for these 4 operating room metrics. This can serve as both a resource for operating room managers to compare their practice to national trends and a tool for strategically identifying at-risk surgical cases. PMID- 27185720 TI - Rett syndrome: a concern for the anesthesiologists. PMID- 27185721 TI - Cardiovascular safety of hydroxypropyl-beta-cyclodextrin-diclofenac in the management of acute postsurgical pain: a pooled analysis of 2 randomized, double blind, placebo- and active comparator-controlled phase III clinical trials. AB - STUDY OBJECTIVE: Long-term use of nonsteroidal anti-inflammatory drugs, including selective and nonselective cyclooxygenase inhibitors, has been suggested to be associated with cardiovascular (CV) safety risks. Data are limited regarding CV risks associated with short-term nonsteroidal anti-inflammatory drug use, including injectable formulations, although it has been suggested that even a single dose may increase CV adverse event (AE) risk. The objective of this study was to examine the CV safety of an injectable diclofenac formulation solubilized with hydroxypropyl-beta-cyclodextrin (HPbetaCD) when given for <=5days postoperatively. DESIGN: A pooled analysis of CV AEs from 2 pivotal phase III clinical trials examining the efficacy and safety of intravenous (IV) HPbetaCD diclofenac vs placebo and the active comparator ketorolac was conducted. SETTING: Postoperative, with treatment initiated in the postanesthesia care unit <=6hours postsurgery. PATIENTS: Overall, 608 abdominal/pelvic and orthopedic surgery patients met inclusion criteria and received >=1 study medication dose. INTERVENTIONS: Patients received either HPbetaCD-diclofenac, ketorolac, or placebo via IV bolus injection every 6hours, for <=5days postsurgery. MEASUREMENTS: CV AEs, reported by study investigators, were evaluated through the treatment period and follow-up (<=37days after last study medication dose), and relative CV AE risks were estimated. MAIN RESULTS: IV HPbetaCD-diclofenac was not associated with increased treatment-emergent CV AE incidence vs placebo (11.6% vs 12.2%; relative risk, 0.96 [95% confidence interval, 0.56-1.62]). Serious CV AEs as well as treatment-related AEs were uncommon, and there were no reports of myocardial infarction or cerebrovascular accident. CV AEs were uncommon during the follow-up period, occurring in 1.3%, 0%, and 1.4% of patients in the HPbetaCD diclofenac, ketorolac, and placebo groups, respectively. CONCLUSIONS: Although a longer duration follow-up study in a larger patient population would expand our understanding of potential CV risks, the present analysis suggests that postoperative use of HPbetaCD-diclofenac does not present an added CV safety risk over placebo. PMID- 27185722 TI - Anesthetic management of donor nephrectomy for a recipient with history of malignant hyperthermia: avoiding a transferred trigger. AB - We describe a case of living unrelated renal transplantation from a non-malignant hyperthermia (MH) susceptible donor to an MH-susceptible recipient, along with its intraoperative and perioperative considerations. The renal transplant recipient reported a personal history of MH requiring intensive care unit admission. A nontriggering anesthetic was therefore chosen for the unrelated donor to avoid possible triggering via the transplanted kidney to the MH susceptible recipient. This case provides a unique opportunity to review the concepts of antigen transfer related to transplant anesthesia, as well as the importance of communication among anesthesia and surgical teams to promote patient safety. PMID- 27185723 TI - Use of the new supraglottic device "Ambu AuraGain" in clinical settings. PMID- 27185724 TI - Asystole during lumbar discectomy: a case report. AB - Hemodynamic derangements have been reported after surgery involving upper cervical spine. Similar observations, however, are rare during a lumbar spine surgery. We share our experience in a patient who had 2 episodes of bradycardia leading to transient asystole while undergoing lumbar discectomy for prolapsed intervertebral disc. The risk of life-threatening hemodynamic disturbances during seemingly uncomplicated surgery in prone position has been emphasized. PMID- 27185725 TI - The efficacy of labetalol vs dexmedetomidine for attenuation of hemodynamic stress response to laryngoscopy and endotracheal intubation. AB - OBJECTIVE: To assess the effectiveness of labetalol vs dexmedetomidine for attenuation of hemodynamic stress response to laryngoscopy and endotracheal intubation. DESIGN: Prospective, randomized, controlled, observer-blinded study. SETTING: This study was carried out in Tanta University Hospital. PATIENTS: Ninety patients of both sexes; American Society of Anesthesiologists physical status I and II; age range from 20 to 60 years; scheduled for elective surgery under general anesthesia. INTERVENTIONS: Patients were divided into 3 groups (30 each). Group A received 1 MUg/kg of dexmedetomidine as intravenous (IV) infusion, group B received labetalol 0.25mg/kg IV, and group C received 10mL saline IV. MEASUREMENTS: The groups were compared for heart rate (HR), mean arterial pressure (MAP), and rate pressure product (RPP). Hemodynamic parameters were recorded during the preinduction; after induction; at intubation; and at 1, 3, 5, 10, and 15minutes. The primary outcomes were hemodynamic changes (HR, MBP, and RPP), and the secondary outcome was propofol dose requirement for induction of general anaesthesia. RESULTS: Significant decrease (P < .05) in HR, MBP, and RPP in groups A and B in comparison with group C and in group A in comparison with group B. Just before intubation, there was a significant decrease (P < .05) in HR, MBP, and RPP in groups A and B in comparison with group C. In group C, there was a significant increase in HR, MBP, and RPP at all points when compared with the baseline. In group A, the mean propofol induction dose (mg) was statistically significantly low as compared with that in groups B and C. CONCLUSION: Dexmedetomidine attenuates the hemodynamic stress response to laryngoscopy and intubation more effectively compared with labetalol without any deleterious effects. Furthermore, dexmedetomidine decreases dose of propofol for induction of anesthesia as guided by bispectral index. PMID- 27185726 TI - Bone cement implantation syndrome: a delayed postoperative presentation. AB - Bone cement implantation syndrome (BCIS) is a well-known entity but is poorly understood and rarely reported. It is an important cause of perioperative morbidity and mortality in the patient undergoing cemented hip arthroplasty. BCIS is characterized by hypotension, hypoxia, cardiac arrhythmias, and increased pulmonary vascular resistance and can lead to eventual cardiac arrest if not managed properly. We hereby report a case of delayed presentation of BCIS following cemented right hip arthroplasty. PMID- 27185727 TI - Preanesthetic evaluation of a patient with a deep brain stimulator: a practical guide and checklist for patient safety. AB - As the patient population with deep brain stimulators grows, medical personnel need to be comfortable managing these patients because they will likely encounter them in practice. Caring for a patient with a deep brain stimulator during surgery or a procedure requires technical knowledge of the device and its possible interactions in order to take the correct precautionary measures. Here we discuss the key issues and questions that should be covered in every preanesthetic evaluation visit of a patient with a deep brain stimulator along with an evaluation checklist. PMID- 27185728 TI - Inclusion body myositis and anesthesia: a case series. AB - STUDY OBJECTIVE: Inclusion body myositis is a painless inflammatory myopathy affecting older adults. It manifests as progressive muscle atrophy and weakness, typically affecting proximal lower extremity muscles initially but insidiously progressing to affect other muscles, including bulbar (oropharyngeal) muscles and the diaphragm, and leading to dysphagia and respiratory insufficiency. This study reviews the perioperative outcomes of patients with inclusion body myositis who received general anesthesia. DESIGN: Observational retrospective study. SETTING: Academic tertiary referral center. PATIENTS: Patients with inclusion body myositis from October 1, 2009, to September 30, 2015, undergoing procedures requiring general anesthesia. INTERVENTIONS: Perioperative health records were reviewed. MEASUREMENTS: Perioperative outcomes and complications were assessed, with emphasis on respiratory complications and unexpected reactions to succinylcholine and nondepolarizing neuromuscular blocking drugs. MAIN RESULTS: Sixteen patients with inclusion body myositis underwent 18 procedures requiring general anesthesia. Succinylcholine was used during induction in 6 cases (33.3%) and nondepolarizing neuromuscular blocking drugs in 11 cases (61.1%). For 13 patients (72.2%), the trachea was extubated at the end of surgery, and none had postoperative respiratory complications. The 5 patients who continued to have tracheal intubation were expected to require continuous mechanical ventilation postoperatively. Three patients died within 30 days of surgery. One patient underwent a tracheostomy for planned long-term mechanical ventilation but life support was withdrawn after 22 days, and 2 severely deconditioned patients died at 11 and 15 days following general anesthesia for endoscopic procedures. CONCLUSIONS: Our patients with inclusion body myositis had uneventful perioperative outcomes following general anesthesia with depolarizing and nondepolarizing muscle relaxants. The small patient cohort in our series precludes a definitive conclusion regarding the safety of anesthetic agents in this patient population. PMID- 27185729 TI - One-lung ventilation in tracheostomized patients: our experience with EZ-Blocker. PMID- 27185730 TI - Gastric tube-guided insertion of laryngeal tube suction. PMID- 27185731 TI - Gestational hypertension and chronic hypertension on the risk of diabetes among gestational diabetes women. AB - AIMS: We aimed to examine the association of gestational hypertension and chronic hypertension at the inter-conception examination with type 2 diabetes risk among women with a history of gestational diabetes. METHODS: We conducted a population based study among 1261 women who had a history of gestational diabetes at 1 5years after delivery in Tianjin, China. Logistic regression or Cox regression was used to assess the associations of gestational hypertension and chronic hypertension at the inter-conception examination with pre-diabetes and type 2 diabetes risks. RESULTS: Gestational diabetic women who had a history of gestational hypertension but did not use antihypertensive drugs during pregnancy had a 3.94-fold higher risk (95% CI: 1.94-8.02) of developing type 2 diabetes compared with those who were normotensive in index pregnancy. Compared with gestational diabetic women who had normal blood pressure at the inter-conception examination, hypertensive women at the inter-conception examination were 3.38 times (95% CI: 1.66-6.87) and 2.97 times (95% CI: 1.75-5.05) more likely to develop diabetes and prediabetes, respectively. The odds ratios of type 2 diabetes and prediabetes associated with each 5mmHg increase in systolic blood pressure were 1.25 (95% CI: 1.03-1.51) and 1.20 (95% CI: 1.06-1.35). Each 5mmHg increase in diastolic blood pressure contributed to a 1.49-fold higher risk (95% CI: 1.18-1.88) for type 2 diabetes and a 1.42-fold higher risk (95% CI: 1.22 1.65) for prediabetes. CONCLUSIONS: For women with prior gestational diabetes, gestational hypertension and chronic hypertension at the inter-conception examination were risk factors for type 2 diabetes. PMID- 27185733 TI - Fatal Neonatal Peritoneal Candidiasis Mimicking Mucormycosis-A Case Report and Review of Literature. AB - Candida species have been implicated as significant contributors to morbidity in the neonatal period and are associated with 25-50% of mortality in invasive neonatal candidiasis. Peritoneal candidiasis, being paucisymptomatic, cannot often be correctly identified in a preterm neonate. The correct approach to diagnosis of neonatal peritoneal candidiasis is taking into account the epidemiology along with a strong clinical suspicion and appropriate timely diagnostic interventions. We report a case of fatal neonatal peritoneal candidiasis which was misdiagnosed as mucormycosis. PMID- 27185732 TI - The Drosophila HNF4 nuclear receptor promotes glucose-stimulated insulin secretion and mitochondrial function in adults. AB - Although mutations in HNF4A were identified as the cause of Maturity Onset Diabetes of the Young 1 (MODY1) two decades ago, the mechanisms by which this nuclear receptor regulates glucose homeostasis remain unclear. Here we report that loss of Drosophila HNF4 recapitulates hallmark symptoms of MODY1, including adult-onset hyperglycemia, glucose intolerance and impaired glucose-stimulated insulin secretion (GSIS). These defects are linked to a role for dHNF4 in promoting mitochondrial function as well as the expression of Hex-C, a homolog of the MODY2 gene Glucokinase. dHNF4 is required in the fat body and insulin producing cells to maintain glucose homeostasis by supporting a developmental switch toward oxidative phosphorylation and GSIS at the transition to adulthood. These findings establish an animal model for MODY1 and define a developmental reprogramming of metabolism to support the energetic needs of the mature animal. PMID- 27185736 TI - Memory-enhancing effects of Cuscuta japonica Choisy via enhancement of adult hippocampal neurogenesis in mice. AB - It is generally accepted that functional and structural changes within the hippocampus are involved in learning and memory and that adult neurogenesis in this region may modulate cognition. The extract of Cuscuta japonica Choisy (CJ) is a well-known traditional Chinese herbal medicine that has been used since ancient times as a rejuvenation remedy. The systemic effects of this herb are widely known and can be applied for the treatment of a number of physiological diseases, but there is a lack of evidence describing its effects on brain function. Thus, the present study investigated whether CJ would enhance memory function and/or increase hippocampal neurogenesis using mice orally administered with CJ water extract or vehicle for 21days. Performance on the novel object recognition and passive avoidance tests revealed that treatment with CJ dose dependently improved the cognitive function of mice. Additionally, CJ increased the Ki-67-positive proliferating cells and the number of doublecortin-stained neuroblasts in the dentate gyrus (DG) of the hippocampus, and double labeling with 5-bromo-2-deoxyuridine and neuronal specific nuclear protein showed that CJ increased the number of mature neurons in the DG. Finally, CJ resulted in the upregulated expression of neurogenic differentiation factor, which is essential for the maturation and differentiation of granule cells in the hippocampus. Taken together, the present findings indicate that CJ stimulated neuronal cell proliferation, differentiation, and maturation, which are all processes associated with neurogenesis. Additionally, these findings suggest that CJ may improve learning and memory via the enhancement of adult hippocampal neurogenesis. PMID- 27185735 TI - Is there an association between hypercholesterolemia and depression? Behavioral evidence from the LDLr(-/-) mouse experimental model. AB - Although epidemiological studies have reported an association between hypercholesterolemia and mood disorders, there is a lack of data regarding depressive-like behavior in animal models of hypercholesterolemia. To address these questions, we assessed depressive-like behavior and hippocampal and cortical monoaminergic metabolism in three-month-old, low-density lipoprotein receptor knockout (LDLr(-/-)) and C57BL/6 wild-type mice. The LDLr(-/-) mice exhibited depressive-like behavior in the sucrose preference test, splash test, and tail suspension test. Increased monoamine oxidase (MAO) A and B activity was evidenced in the hippocampus of LDLr(-/-) mice. Furthermore, to address whether or not cholesterol modulates MAO activity, we exposed SH-SY5Y human neuroblastoma cells to human isolated low-density lipoprotein (LDL). Notably, LDL increased the activity of MAO-A and stimulated the reactive species generation in vitro. These findings indicate that depressive-like behavior in hypercholesterolemic mice is accompanied by alterations in the monoaminergic metabolism, providing new evidence about the association between hypercholesterolemia and depression. PMID- 27185737 TI - The optimal timing of stimulation to induce long-lasting positive effects on episodic memory in physiological aging. AB - Episodic memory displays the largest degree of age-related decline. A noninvasive brain stimulation technique that can be used to modulate memory in physiological aging is transcranial Direct Current Stimulation (tDCS). However, an aspect that has not been adequately investigated in previous studies is the optimal timing of stimulation to induce long-lasting positive effects on episodic memory function. Our previous studies showed episodic memory enhancement in older adults when anodal tDCS was applied over the left lateral prefrontal cortex during encoding or after memory consolidation with or without a contextual reminder. Here we directly compared the two studies to explore which of the tDCS protocols would induce longer-lasting positive effects on episodic memory function in older adults. In addition, we aimed to determine whether subjective memory complaints would be related to the changes in memory performance (forgetting) induced by tDCS, a relevant issue in aging research since individuals with subjective memory complaints seem to be at higher risk of later memory decline. The results showed that anodal tDCS applied after consolidation with a contextual reminder induced longer-lasting positive effects on episodic memory, conceivably through reconsolidation, than anodal tDCS during encoding. Furthermore, we reported, providing new data, a moderate negative correlation between subjective memory complaints and forgetting when anodal tDCS was applied after consolidation with a contextual reminder. This study sheds light on the best-suited timing of stimulation to induce long-lasting positive effects on memory function and might help the clinicians to select the most effective tDCS protocol to prevent memory decline. PMID- 27185738 TI - Differential response to anodal tDCS and PAS is indicative of impaired focal LTP like plasticity in schizophrenia. AB - Increasing evidence suggests that neural plasticity impairments, observed in schizophrenia patients, are driven by dysfunctional integration of neural signaling. However, what is less clear is whether this impairment is resultant from a general deficit in plastic induction or whether a specific plastic mechanism is affected. In the current study we aimed to assess whether schizophrenia has a selective impact on focal or non-focal plasticity induction. To pursue this goal we utilized two non-invasive stimulation techniques that differ in the mechanism of long-term potentiation (LTP)-like plasticity induction: focal paired associative stimulation (PAS) and non-focal anodal transcranial direct current stimulation (a-tDCS). 20 schizophrenia patients and 20 matched healthy controls received PAS and a-tDCS in two separate sessions. Cortical excitability and cortical plasticity were assessed by transcranial magnetic stimulation (TMS)-elicited motor evoked potentials (MEP). In both study groups, non-focal a-tDCS resulted in a significant increase of mean MEP magnitude indicating the successful induction of non-focal LTP-like plasticity. In contrast, an increase in mean MEP magnitude following PAS was only observed in the control group, suggesting impaired focal LTP-like plasticity in schizophrenia. Additionally, we observed significantly impaired short-latency intracortical inhibition (SICI) in schizophrenia. This is the first study to comparatively evaluate non-focal and focal plasticity mechanisms in schizophrenia patients. The differential patterns of LTP-like plasticity responses indicate that reduced plasticity in schizophrenia could be ascribed to impairments in spatially and temporally restricted signal integration. This impairment, coupled with an observed reduction of inhibitory circuit efficacy, might further contribute to impairments in coordinating focal signals. PMID- 27185734 TI - Molecular and cellular pathophysiology of preclinical Alzheimer's disease. AB - Although the two pathological hallmarks of Alzheimer's disease (AD), senile plaques composed of amyloid-beta (Abeta) peptides and neurofibrillary tangles (NFTs) consisting of hyperphosphorylated tau, have been studied extensively in postmortem AD and relevant animal and cellular models, the pathogenesis of AD remains unknown, particularly in the early stages of the disease where therapies presumably would be most effective. We and others have demonstrated that Abeta plaques and NFTs are present in varying degrees before the onset and throughout the progression of dementia. In this regard, aged people with no cognitive impairment (NCI), mild cognitive impairment (MCI, a presumed prodromal AD transitional state, and AD all present at autopsy with varying levels of pathological hallmarks. Cognitive decline, a requisite for the clinical diagnosis of dementia associated with AD, generally correlates better with NFTs than Abeta plaques. However, correlations are even higher between cognitive decline and synaptic loss. In this review, we illustrate relevant clinical pathological research in preclinical AD and throughout the progression of dementia in several areas including Abeta and tau pathobiology, single population expression profiling of vulnerable hippocampal and basal forebrain neurons, neuroplasticity, neuroimaging, cerebrospinal fluid (CSF) biomarker studies and their correlation with antemortem cognitive endpoints. In each of these areas, we provide evidence for the importance of studying the pathological hallmarks of AD not in isolation, but rather in conjunction with other molecular, cellular, and imaging markers to provide a more systematic and comprehensive assessment of the multiple changes that occur during the transition from NCI to MCI to frank AD. PMID- 27185740 TI - Kinematic Effects of Nickel-Titanium Instruments with Reciprocating or Continuous Rotation Motion: A Systematic Review of In Vitro Studies. AB - INTRODUCTION: This review aimed to compare the kinematic effect of nickel titanium instruments with reciprocating and continuous rotation motion for cyclic fatigue resistance, shaping ability, apical debris extrusion, and dentinal defects or cracks. METHOD: Articles were selected for inclusion in this review if they fulfilled all of the following criteria: described in vitro studies performed on either extracted human teeth or an artificial canal model, assessed both reciprocating and rotary instruments, compared reciprocating files and rotary files for the kinematics of files, and evaluated reciprocating and rotary files regarding the aim of this study. The electronic search was undertaken in MEDLINE, Cochrane database, and manual searches, including journals, reference lists, and other reviews. RESULTS: Twelve studies were chosen for cyclic fatigue, 19 studies for shaping ability, 14 studies for apical debris extrusion, and 13 studies for dentinal defects or cracks. Most of the studies showed that reciprocating motion had a higher resistance to cyclic fatigue. Nine studies from the shaping studies reported less canal transportation by using the reciprocating motion than the continuous rotation. The reciprocating instruments tended to extrude more dentin debris than the continuous rotating instruments, but many of the studies showed conflicting results. In addition, 2 studies from the defects or cracks studies claimed the reciprocating motion produced more dentinal defects than the continuous rotating motion. CONCLUSIONS: Instruments with reciprocating motion seemed to have better resistance to cyclic fatigue with less canal transportation tendency than the instruments with continuous rotating motion. PMID- 27185739 TI - Acute alcohol exposure during neurulation: Behavioral and brain structural consequences in adolescent C57BL/6J mice. AB - Prenatal alcohol exposure (PAE) can induce physical malformations and behavioral abnormalities that depend in part on thedevelopmental timing of alcohol exposure. The current studies employed a mouse FASD model to characterize the long-term behavioral and brain structural consequences of a binge-like alcohol exposure during neurulation; a first-trimester stage when women are typically unaware that they are pregnant. Time-mated C57BL/6J female mice were administered two alcohol doses (2.8g/kg, four hours apart) or vehicle starting at gestational day 8.0. Male and female adolescent offspring (postnatal day 28-45) were then examined for motor activity (open field and elevated plus maze), coordination (rotarod), spatial learning and memory (Morris water maze), sensory motor gating (acoustic startle and prepulse inhibition), sociability (three-chambered social test), and nociceptive responses (hot plate). Regional brain volumes and shapes were determined using magnetic resonance imaging. In males, PAE increased activity on the elevated plus maze and reduced social novelty preference, while in females PAE increased exploratory behavior in the open field and transiently impaired rotarod performance. In both males and females, PAE modestly impaired Morris water maze performance and decreased the latency to respond on the hot plate. There were no brain volume differences; however, significant shape differences were found in the cerebellum, hypothalamus, striatum, and corpus callosum. These results demonstrate that alcohol exposure during neurulation can have functional consequences into adolescence, even in the absence of significant brain regional volumetric changes. However, PAE-induced regional shape changes provide evidence for persistent brain alterations and suggest alternative clinical diagnostic markers. PMID- 27185742 TI - Effects of applied potential and the initial gap between electrodes on localized electrochemical deposition of micrometer copper columns. AB - Micrometer copper columns were fabricated via a technology named localized electrochemical deposition (LECD). This paper studies the effects of applied potential and the initial gap between electrodes on the LECD process. The surface and cross sectional morphologies, as well as the average deposition rate were investigated to evaluate the quality of the deposited copper columns. Results demonstrated that the copper columns tended to be cylinder-shape with few voids inside at lower potential (<2.4 V). Whereas,the copper columns tended to be dendriform-shape with lots of voids inside at larger potential (>2.8 V). The average deposition rate increased with the raise of potential. In addition, the copper columns tended to be cylinder-shape with the initial gap between electrodes to be 10 MUm or below. However, the copper columns tended to be cone shape when the initial gap between electrodes became larger (35 MUm or above). The number of voids inside the copper column and the average deposition rate both decreased with the increase of the initial gap. Moreover, the process of LECD under varied electric field has also been simulated using COMSOL software, and the formation of cylindrical and conical copper columns was further explained based on the electric field distribution at the cathode. PMID- 27185743 TI - Reply. PMID- 27185741 TI - Elizabethkingia anophelis bacteremia is associated with clinically significant infections and high mortality. AB - Unlike Elizabethkingia meningoseptica, the clinical importance of E. anophelis is poorly understood. We determined the clinical and molecular epidemiology of bacteremia caused by Elizabethkingia-like species from five regional hospitals in Hong Kong. Among 45 episodes of Elizabethkingia-like bacteremia, 21 were caused by Elizabethkingia, including 17 E. anophelis, three E. meningoseptica and one E. miricola; while 24 were caused by other diverse genera/species, as determined by 16S rRNA gene sequencing. Of the 17 cases of E. anophelis bacteremia, 15 (88%) were clinically significant. The most common diagnosis was pneumonia (n = 5), followed by catheter-related bacteremia (n = 4), neonatal meningitis (n = 3), nosocomial bacteremia (n = 2) and neutropenic fever (n = 1). E. anophelis bacteremia was commonly associated with complications and carried 23.5% mortality. In contrast, of the 24 episodes of bacteremia due to non Elizabethkingia species, 16 (67%) were clinically insignificant. Compared to non Elizabethkingia bacteremia, Elizabethkingia bacteremia was associated with more clinically significant infections (P < 0.01) and positive cultures from other sites (P < 0.01), less polymicrobial bacteremia (P < 0.01), and higher complication (P < 0.05) and mortality (P < 0.05) rates. Elizabethkingia bacteremia is predominantly caused by E. anophelis instead of E. meningoseptica. Elizabethkingia bacteremia, especially due to E. anophelis, carries significant morbidity and mortality, and should be considered clinically significant unless proven otherwise. PMID- 27185744 TI - FRET-Protease-Coupled Peptidyl-Prolyl cis-trans Isomerase Assay: New Internally Quenched Fluorogenic Substrates for High-Throughput Screening. AB - In this work, a sensitive and convenient protease-based fluorimetric high throughput screening (HTS) assay for determining peptidyl-prolyl cis-trans isomerase activity was developed. The assay was based on a new intramolecularly quenched substrate, whose fluorescence and structural properties were examined together with kinetic constants and the effects of solvents on its isomerization process. Pilot screens performed using the Library of Pharmacologically Active Compounds (LOPAC) and cyclophilin A (CypA), as isomerase model enzyme, indicated that the assay was robust for HTS, and that comparable results were obtained with a CypA inhibitor tested both manually and automatically. Moreover, a new compound that inhibits CypA activity with an IC50 in the low micromolar range was identified. Molecular docking studies revealed that the molecule shows a notable shape complementarity with the catalytic pocket confirming the experimental observations. Due to its simplicity and precision in the determination of extent of inhibition and reaction rates required for kinetic analysis, this assay offers many advantages over other commonly used assays. PMID- 27185745 TI - Tackling causes and costs of ED presentation for American football injuries: a population-level study. AB - BACKGROUND: American tackle football is the most popular high-energy impact sport in the United States, with approximately 9 million participants competing annually. Previous epidemiologic studies of football-related injuries have generally focused on specific geographic areas or pediatric age groups. Our study sought to examine patient characteristics and outcomes, including hospital charges, among athletes presenting for emergency department (ED) treatment of football-related injury across all age groups in a large nationally representative data set. METHODS: Patients presenting for ED treatment of injuries sustained playing American tackle football (identified using International Classification of Diseases, Ninth Revision, Clinical Modification code E007.0) from 2010 to 2011 were studied in the Nationwide Emergency Department Sample. Patient-specific injuries were identified using the primary International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code and categorized by type and anatomical region. Standard descriptive methods examined patient demographics, diagnosis categories, and ED and inpatient outcomes and charges. RESULTS: During the study period 397363 football players presented for ED treatment, 95.8% of whom were male. Sprains/strains (25.6%), limb fractures (20.7%), and head injuries (including traumatic brain injury; 17.5%) represented the most presenting injuries. Overall, 97.9% of patients underwent routine ED discharge with 1.1% admitted directly and fewer than 11 patients in the 2-year study period dying prior to discharge. The proportion of admitted patients who required surgical interventions was 15.7%, of which 89.9% were orthopedic, 4.7% neurologic, and 2.6% abdominal. Among individuals admitted to inpatient care, mean hospital length of stay was 2.4days (95% confidence interval, 2.2-2.6) and 95.6% underwent routine discharge home. The mean total charge for all patients was $1941 (95% confidence interval, $1890 $1992) with substantial injury type-specific variability. Overall, at the US population, estimated total charges of $771299862 were incurred over the 2-year period. CONCLUSION: In this nationally representative sample, most ED-treated injuries associated with football were not acutely life threatening and very few required major therapeutic intervention. This study provides a cross-sectional overview of ED presentation for acute football-related injury across age groups at the population level in recent years. Longitudinal studies may be warranted to examine associations between the patterns of injury observed in this study and long-term outcomes among American tackle football players. PMID- 27185747 TI - Blood Pressure Measurement in the Post-SPRINT Era: A Canadian Perspective. PMID- 27185746 TI - Masked Hypertension and Incident Clinic Hypertension Among Blacks in the Jackson Heart Study. AB - Masked hypertension, defined as nonelevated clinic blood pressure (BP) and elevated out-of-clinic BP may be an intermediary stage in the progression from normotension to hypertension. We examined the associations of out-of-clinic BP and masked hypertension using ambulatory BP monitoring with incident clinic hypertension in the Jackson Heart Study, a prospective cohort of blacks. Analyses included 317 participants with clinic BP <140/90 mm Hg, complete ambulatory BP monitoring, who were not taking antihypertensive medication at baseline in 2000 to 2004. Masked daytime hypertension was defined as mean daytime blood pressure >=135/85 mm Hg, masked night-time hypertension as mean night-time BP >=120/70 mm Hg, and masked 24-hour hypertension as mean 24-hour BP >=130/80 mm Hg. Incident clinic hypertension, assessed at study visits in 2005 to 2008 and 2009 to 2012, was defined as the first visit with clinic systolic/diastolic BP >=140/90 mm Hg or antihypertensive medication use. During a median follow-up of 8.1 years, there were 187 (59.0%) incident cases of clinic hypertension. Clinic hypertension developed in 79.2% and 42.2% of participants with and without any masked hypertension, 85.7% and 50.4% with and without masked daytime hypertension, 79.9% and 43.7% with and without masked night-time hypertension, and 85.7% and 48.2% with and without masked 24-hour hypertension, respectively. Multivariable adjusted hazard ratios (95% confidence interval) of incident clinic hypertension for any masked hypertension and masked daytime, night-time, and 24-hour hypertension were 2.13 (1.51-3.02), 1.79 (1.24-2.60), 2.22 (1.58-3.12), and 1.91 (1.32-2.75), respectively. These findings suggest that ambulatory BP monitoring can identify blacks at increased risk for developing clinic hypertension. PMID- 27185749 TI - What Is the Significance of Masked Hypertension Versus Incident Hypertension in Blacks? PMID- 27185750 TI - Mechanisms of Hypertension and Renal Injury During Vascular Endothelial Growth Factor Signaling Inhibition. PMID- 27185748 TI - Renal Denervation Improves Exaggerated Sympathoexcitation in Rats With Heart Failure: A Role for Neuronal Nitric Oxide Synthase in the Paraventricular Nucleus. AB - Renal denervation (RDN) has been postulated to reduce sympathetic drive during heart failure (HF), but the central mechanisms are not completely understood. The purpose of the present study was to assess the contribution of neuronal nitric oxide synthase (nNOS) within the paraventricular nucleus (PVN) in modulating sympathetic outflow in rats with HF that underwent RDN. HF was induced in rats by ligation of the left coronary artery. Four weeks after surgery, bilateral RDN was performed. Rats with HF had an increase in FosB-positive cells in the PVN with a concomitant increase in urinary excretion of norepinephrine, and both of these parameters were ameliorated after RDN. nNOS-positive cells immunostaining, diaphorase staining, and nNOS protein expression were significantly decreased in the PVN of HF rats, findings that were ameliorated by RDN. Microinjection of nNOS inhibitor N(G)-monomethyl l-arginine into the PVN resulted in a blunted increase in lumbar sympathetic nerve activity (11+/-2% versus 24+/-2%) in HF than in sham group. This response was normalized after RDN. Stimulation of afferent renal nerves produced a greater activation of PVN neurons in rats with HF. Afferent renal nerve stimulation elicited a greater increase in lumbar sympathetic nerve activity in rats with HF than in sham rats (45+/-5% versus 22+/-2%). These results suggest that intact renal nerves contribute to the reduction of nNOS in the PVN, resulting in the activation of the neurons in the PVN of rats with HF. RDN restores nNOS and thus attenuates the sympathoexcitation commonly observed in HF. PMID- 27185752 TI - Post-Control of Hypertension in Pregnancy Study (CHIPS): What Is the Optimal Strategy to Manage Hypertension During Pregnancy? PMID- 27185751 TI - Adipocyte (Pro)Renin-Receptor Deficiency Induces Lipodystrophy, Liver Steatosis and Increases Blood Pressure in Male Mice. AB - Adipose tissue dysfunction related to obesity is overwhelmingly associated with increased risk of developing cardiovascular diseases. In the setting of obesity, (pro)renin receptor (PRR) is increased in adipose tissue of mice. We sought to determine the physiological consequences of adipocyte-PRR deficiency using adiponectin-Cre mice. We report a unique model of adipocyte-PRR-deficient mice (PRR(Adi/Y)) with almost no detectable white adipose tissues. As a consequence, the livers of PRR(Adi/Y) mice were enlarged and demonstrated a marked accumulation of lipids. Adipocyte-specific deficiency of PRR increased systolic blood pressure and the concentration of soluble PRR in plasma. To determine whether adipocyte-PRR was involved in the development of obesity-induced hypertension, mice were fed a low-fat or a high-fat diet for 16 weeks. Adipocyte PRR-deficient mice were resistant to diet-induced obesity. Both high-fat- and low fat-fed PRR(Adi/Y) mice had elevated insulin levels. Interestingly, adipocyte-PRR deficiency improved glucose tolerance in high-fat-fed PRR(Adi/Y) mice. In response to feeding either low-fat or high-fat diets, systolic blood pressure was greater in PRR(Adi/Y) mice than in control mice. High-fat feeding elevated soluble PRR concentration in control and PRR(Adi/Y) mice. In vitro knockdown of PRR by siRNA significantly decreased mRNA abundance of PPARgamma (peroxisome proliferator-activated receptor gamma), suggesting an important role for PRR in adipogenesis. Our data indicate that adipocyte-PRR is involved in lipid homeostasis and glucose and insulin homeostasis, and that soluble PRR may be a predictor of metabolic disturbances and play a role in systolic blood pressure regulation. PMID- 27185753 TI - WITHDRAWN: Impact of Initial Antibiotic Selection on Adverse Outcomes Among Patients With Severe Sepsis and Septic Shock. AB - The Publisher regrets that this article is an accidental duplication of an article that has already been published in Crit Care Med, 43 (2015) 263, http://dx.doi.org/10.1097/01.ccm.0000474875.35054.b3. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. PMID- 27185755 TI - End coming for misunderstood CMA House. PMID- 27185754 TI - Biases in detection of apparent "weekend effect" on outcome with administrative coding data: population based study of stroke. AB - OBJECTIVES: To determine the accuracy of coding of admissions for stroke on weekdays versus weekends and any impact on apparent outcome. DESIGN: Prospective population based stroke incidence study and a scoping review of previous studies of weekend effects in stroke. SETTING: Primary and secondary care of all individuals registered with nine general practices in Oxfordshire, United Kingdom (OXVASC, the Oxford Vascular Study). PARTICIPANTS: All patients with clinically confirmed acute stroke in OXVASC identified with multiple overlapping methods of ascertainment in 2002-14 versus all acute stroke admissions identified by hospital diagnostic and mortality coding alone during the same period. MAIN OUTCOMES MEASURES: Accuracy of administrative coding data for all patients with confirmed stroke admitted to hospital in OXVASC. Difference between rates of "false positive" or "false negative" coding for weekday and weekend admissions. Impact of inaccurate coding on apparent case fatality at 30 days in weekday versus weekend admissions. Weekend effects on outcomes in patients with confirmed stroke admitted to hospital in OXVASC and impacts of other potential biases compared with those in the scoping review. RESULTS: Among 92 728 study population, 2373 episodes of acute stroke were ascertained in OXVASC, of which 826 (34.8%) mainly minor events were managed without hospital admission, 60 (2.5%) occurred out of the area or abroad, and 195 (8.2%) occurred in hospital during an admission for a different reason. Of 1292 local hospital admissions for acute stroke, 973 (75.3%) were correctly identified by administrative coding. There was no bias in distribution of weekend versus weekday admission of the 319 strokes missed by coding. Of 1693 admissions for stroke identified by coding, 1055 (62.3%) were confirmed to be acute strokes after case adjudication. Among the 638 false positive coded cases, patients were more likely to be admitted on weekdays than at weekends (536 (41.0%) v 102 (26.5%); P<0.001), partly because of weekday elective admissions after previous stroke being miscoded as new stroke episodes (267 (49.8%) v 26 (25.5%); P<0.001). The 30 day case fatality after these elective admissions was lower than after confirmed acute stroke admissions (11 (3.8%) v 233 (22.1%); P<0.001). Consequently, relative 30 day case fatality for weekend versus weekday admissions differed (P<0.001) between correctly coded acute stroke admissions and false positive coding cases. Results were consistent when only the 1327 emergency cases identified by "admission method" from coding were included, with more false positive cases with low case fatality (35 (14.7%)) being included for weekday versus weekend admissions (190 (19.5%) v 48 (13.7%), P<0.02). Among all acute stroke admissions in OXVASC, there was no imbalance in baseline stroke severity for weekends versus weekdays and no difference in case fatality at 30 days (adjusted odds ratio 0.85, 95% confidence interval 0.63 to 1.15; P=0.30) or any adverse "weekend effect" on modified Rankin score at 30 days (0.78, 0.61 to 0.99; P=0.04) or one year (0.76, 0.59 to 0.98; P=0.03) among incident strokes. CONCLUSION: Retrospective studies of UK administrative hospital coding data to determine "weekend effects" on outcome in acute medical conditions, such as stroke, can be undermined by inaccurate coding, which can introduce biases that cannot be reliably dealt with by adjustment for case mix. PMID- 27185757 TI - CIHR hikes grants to young researchers. PMID- 27185756 TI - Multilesional cutaneous leishmaniasis. PMID- 27185759 TI - Patents, profit and the public good: the caseof a 19th-century artificial limb manufacturer. PMID- 27185758 TI - A four-month-old boy with bilateral undescended testes. PMID- 27185760 TI - Consensus mounts for national drug formulary. PMID- 27185761 TI - Fort McMurray evacuates patients in "surreal" flight. PMID- 27185762 TI - International legal barriers to Canada's marijuana plans. PMID- 27185763 TI - The weekend effect: now you see it, now you don't. PMID- 27185764 TI - Making evidence based medicine work for individual patients. PMID- 27185766 TI - Historical Review: Problematic Malaria Prophylaxis with Quinine. AB - Quinine, a bitter-tasting, short-acting alkaloid drug extracted from cinchona bark, was the first drug used widely for malaria chemoprophylaxis from the 19th century. Compliance was difficult to enforce even in organized groups such as the military, and its prophylaxis potential was often questioned. Severe adverse events such as blackwater fever occurred rarely, but its relationship to quinine remains uncertain. Quinine prophylaxis was often counterproductive from a public health viewpoint as it left large numbers of persons with suppressed infections producing gametocytes infective for mosquitoes. Quinine was supplied by the first global pharmaceutical cartel which discouraged competition resulting in a near monopoly of cinchona plantations on the island of Java which were closed to Allied use when the Japanese Imperial Army captured Indonesia in 1942. The problems with quinine as a chemoprophylactic drug illustrate the difficulties with medications used for prevention and the acute need for improved compounds. PMID- 27185765 TI - Lethality of First Contact Dysentery Epidemics on Pacific Islands. AB - Infectious diseases depopulated many isolated Pacific islands when they were first exposed to global pathogen circulation from the 18th century. Although the mortality was great, the lack of medical observers makes determination of what happened during these historical epidemics largely speculative. Bacillary dysentery caused by Shigella is the most likely infection causing some of the most lethal island epidemics. The fragmentary historical record is reviewed to gain insight into the possible causes of the extreme lethality that was observed during first-contact epidemics in the Pacific. Immune aspects of the early dysentery epidemics and postmeasles infection resulting in subacute inflammatory enteric disease suggest that epidemiologic isolation was the major lethality risk factor on Pacific islands in the 19th century. Other possible risk factors include human leukocyte antigen homogeneity from a founder effect and pathogen induced derangement of immune tolerance to gut flora. If this analysis is correct, then Pacific islands are currently at no greater risk of emerging disease epidemics than other developing countries despite their dark history. PMID- 27185767 TI - Landscape Fragmentation as a Risk Factor for Buruli Ulcer Disease in Ghana. AB - Land cover and its change have been linked to Buruli ulcer (BU), a rapidly emerging tropical disease. However, it is unknown whether landscape structure affects the disease prevalence. To examine the association between landscape pattern and BU presence, we obtained land cover information for 20 villages in southwestern Ghana from high resolution satellite images, and analyzed the landscape pattern surrounding each village. Eight landscape metrics indicated that landscape patterns between BU case and reference villages were different (P < 0.05) at the broad spatial extent examined (4 km). The logistic regression models showed that landscape fragmentation and diversity indices were positively associated with BU presence in a village. Specifically, for each increase in patch density and edge density by 100 units, the likelihood of BU presence in a village increased 2.51 (95% confidence interval [CI] = 1.36-4.61) and 4.18 (95% CI = 1.63-10.76) times, respectively. The results suggest that increased landscape fragmentation may pose a risk to the emergence of BU. PMID- 27185770 TI - US launches $121m microbiome initiative. PMID- 27185769 TI - Nanoparticle-Based Histidine-Rich Protein-2 Assay for the Detection of the Malaria Parasite Plasmodium falciparum. AB - A nanoparticle-based assay for detection and quantification of Plasmodium falciparum histidine-rich protein 2 (HRP2) in urine and serum is reported. The assay uses magnetic beads conjugated with anti-HRP2 antibody for protein capture and concentration, and antibody-conjugated quantum dots for optical detection. Western blot analysis demonstrated that magnetic beads allow the concentration of HRP2 protein in urine by 20-fold. The concentration effect was achieved because large volume of urine can be incubated with beads, and magnetic separation can be easily performed in minutes to isolate beads containing HRP2 protein. Magnetic beads and quantum dots conjugated to anti-HRP2 antibodies allows the detection of low concentrations of HRP2 protein (0.5 ng/mL), and quantification in the range of 33-2,000 ng/mL corresponding to the range associated with non-severe to severe malaria. This assay can be easily adapted to a noninvasive point-of-care test for classification of severe malaria. PMID- 27185768 TI - Evaluation of Commercially Available Assays for Diagnosis of Acute Dengue in Schoolchildren During an Epidemic Period in Medellin, Colombia. AB - During an active surveillance study in school children in Medellin, we assessed the performance of two diagnostic strategies for dengue virus. A total of 41 patients with suspected dengue acute infection were evaluated. Diagnostic strategies consisted of one combining Panbio((r)) Dengue virus IgM and IgG Capture ELISAs (enzyme-linked immunosorbent assays) with reverse transcriptase polymerase chain reaction (RT-PCR) and another using a commercial rapid SD Bioline Dengue Duo (IgG/IgM + NS1 Ag) test. These two strategies were compared with the enzyme-linked immunospot microneutralization test (ELISPOT-MNT). The sensitivity and specificity were 53.9% and 80.0% for the combination of Panbio((r)) ELISAs and RT-PCR tests, and 30.8% and 73.3% for the SD Bioline Duo test, respectively. ELISPOT-MNT detected 16.4% additional cases and revealed the presence of neutralizing antibodies in all the acute samples, evidencing that they were all secondary infections. In contrast, Panbio((r)) and SD Dengue Duo rapid tests only classified 23.0% and 26.9% of the cases as secondary dengue infections, respectively. Cohen's kappa coefficient and McNemar's association tests demonstrated a significant disagreement between the two diagnostic strategies and ELISPOT-MNT. Overall, these results evidence the relatively poor performances of commercial assays for the diagnosis of acute and secondary dengue infections, compared with ELISPOT-MNT, and raise concern about the accuracy of these assays for the diagnostic of dengue in endemic areas. PMID- 27185771 TI - Total or free, that is the question. PMID- 27185772 TI - T-cells fighting B-cell lymphoproliferative malignancies: the emerging field of CD19 CAR T-cell therapy. AB - CAR T-cells are autologous T-cells transduced with a chimeric antigen receptor (CAR). The CAR contains an antigen recognition part (originating from an antibody), a T-cell receptor transmembrane and cytoplasmic signalling part, and one or more co-stimulatory domains. While CAR T-cells can be directed against any tumour target, most experience thus far has been obtained with targeting of the B cell antigen CD19 that is expressed by B-cell acute lymphocytic leukaemia, chronic lymphocytic leukaemia and other B-cell lymphomas. The first clinical results are promising, although there are profound differences in response between patients with different haematological malignancies. Treatment-related side effects have been observed that require specific management. This review will explain the mechanism of action, summarise the experience to date and point out future directions for this hopeful new addition to the therapeutic armamentarium in the treatment of lymphoproliferative B-cell malignancies. PMID- 27185773 TI - Success rate of thyroid remnant ablation for differentiated thyroid cancer based on 5550 MBq post-therapy scan. AB - BACKGROUND: Success rate of thyroid remnant ablation in patients with low-risk differentiated thyroid cancer (DTC) is commonly based on measurement of serum thyroglobulin levels and 185 MBq (5 mCi) diagnostic 131I scanning or neck ultrasound, performed 6-9 months after ablation. In the present study, we report the rates of successful 131I ablation based on a 5550 MBq (150 mCi) post-therapy scan performed 6-9 months after ablation. METHODS: Retrospective cohort study of 77 adult patients with DTC, stage T1-T3, N0 or N1, M0, demonstrating thyroid remnant uptake one week after a 2775 MBq (75 mCi) ablation dose. Six to nine months later, all patients received a 5550 MBq dose of 131I, followed by a post- therapy scan after one week. Complete thyroid ablation was defined as no thyroid remnant uptake and a thyroglobulin level < 0.2 MUg/l after thyroid hormone withdrawal. RESULTS: Thyroid ablation was complete in 20 patients (26%). Forty eight patients (62%) demonstrated persistent remnant uptake. This was associated with thyroglobulin levels > 0.2 MUg/l in 24/48, and positive thyroglobulin antibodies in 4/48 patients. CONCLUSION: Thyroid remnant ablation success assessed by 5550 MBq post-therapy scanning was much lower than reported in studies evaluating ablation success based on 185 MBq diagnostic 131I scanning or neck ultrasound. The latter techniques may be too inaccurate to detect thyroid remnants and thus may not be sufficiently reliable to predict long-term disease outcome. PMID- 27185774 TI - The influence of oral contraceptives on overnight 1 mg dexamethasone suppression test. AB - BACKGROUND: In suspected hypercortisolism, the 1 mg dexamethasone suppression test is the usual initial test. In fertile women, false-positive test results are often due to the use of oral contraceptives. By elevating cortisol-binding globulin these contraceptives increase the total serum cortisol concentration. The aim of this study was to assess the duration and degree of influence of oral contraceptives on the low-dose dexamethasone suppression test. METHODS: Thirteen healthy female volunteers without symptoms or signs of overt hypercortisolism, aged 18-55 years, who were using oral contraceptives, underwent a 1 mg dexamethasone suppression test. Tests were repeated one and six weeks after withdrawal of the contraceptive. In addition, 24-hour urinary cortisol excretion and late-night salivary cortisol were measured. RESULTS: Of the 13 volunteers (62%) eight had inadequate suppression of cortisol by 1 mg dexamethasone while using oral contraceptives. One week after the contraceptive was withdrawn, the number of false-positive results significantly decreased to 1 (8%, p < 0.02). Six weeks after discontinuation, all tests were normal. None of the 24-hour urinary cortisol samples and just one late-night salivary cortisol level was elevated. CONCLUSION: The results of the 1 mg dexamethasone suppression test performed one week after cessation of oral contraceptives are accurate in almost all subjects. In case of inadequate suppression, a second test may be performed after six weeks. In this manner the 1 mg dexamethasone suppression test can reliably be done at the end of a seven-day break from contraceptive use in nearly all cases. PMID- 27185775 TI - Guideline-related barriers to optimal prescription of oral anticoagulants in primary care. AB - Guidelines provide recommendations for antithrombotic treatment to prevent stroke in people with atrial fibrillation, but oral anticoagulant prescriptions in Dutch primary care are often discordant with these recommendations. Suboptimal guideline features (i.e. format and content) have been suggested as a potential explanatory factor for this type of discordance. Therefore, we systematically appraised features of the Dutch general practitioners' (NHG) atrial fibrillation guideline to identify guidelinerelated barriers that may hamper its use in practice. We appraised the guideline's methodological rigour and transparency using the Appraisal of Guidelines, Research and Evaluation (AGREE) II tool. Additionally, we used the Guideline Implementability Appraisal (GLIA) tool to assess the key recommendations on oral anticoagulant prescription. The editorial independence of the guideline group scored highly (88%); scores for other aspects of the guideline's methodological quality were acceptable, ranging from 53% for stakeholder involvement to 67% for clarity of presentation. At the recommendation level, the main implementation obstacles were lack of explicit statements on the quality of underlying evidence, lack of clarity around the strength of recommendations, and the use of ambiguous terms which may hamper operationalisation in electronic systems. Based on our findings we suggest extending stakeholder involvement in the guideline development process, standardising the layout and language of key recommendations, providing monitoring criteria, and preparing electronic implementation parallel with guideline development. We expect this to contribute to optimising the NHG atrial fibrillation guideline, facilitating its implementation in practice, and ultimately to improving antithrombotic treatment and stroke prevention in people with atrial fibrillation. PMID- 27185777 TI - Answer to Photo Quiz: Acute-onset breathlessness after a radiological procedure. PMID- 27185776 TI - Acute-onset breathlessness after a radiological procedure. PMID- 27185778 TI - A haemodialysis patient with progressive leg pain. PMID- 27185779 TI - Answer to Photo Quiz: A haemodialysis patient with progressive leg pain. PMID- 27185780 TI - Things are not always what they seem (other causes of hepato-splenic nodules). PMID- 27185781 TI - Answer to Photo Quiz: Things are not always what they seem (other causes of hepato-splenic nodules). PMID- 27185783 TI - Behcet's disease: ethnicity and associated conditions. PMID- 27185782 TI - Leptospiral meningitis in adults. PMID- 27185784 TI - How Brexit might affect public health. PMID- 27185785 TI - Merozoite Antigens of Plasmodium falciparum Elicit Strain-Transcending Opsonizing Immunity. AB - It is unclear whether naturally acquired immunity to Plasmodium falciparum results from the acquisition of antibodies to multiple, diverse antigens or to fewer, highly conserved antigens. Moreover, the specific antibody functions required for malaria immunity are unknown, and hence informative immunological assays are urgently needed to address these knowledge gaps and guide vaccine development. In this study, we investigated whether merozoite-opsonizing antibodies are associated with protection from malaria in a strain-specific or strain-transcending manner by using a novel field isolate and an immune plasma matched cohort from Papua New Guinea with our validated assay of merozoite phagocytosis. Highly correlated opsonization responses were observed across the 15 parasite strains tested, as were strong associations with protection (composite phagocytosis score across all strains in children uninfected at baseline: hazard ratio of 0.15, 95% confidence interval of 0.04 to 0.63). Opsonizing antibodies had a strong strain-transcending component, and the opsonization of transgenic parasites deficient for MSP3, MSP6, MSPDBL1, or P. falciparum MSP1-19 (PfMSP1-19) was similar to that of wild-type parasites. We have provided the first evidence that merozoite opsonization is predominantly strain transcending, and the highly consistent associations with protection against diverse parasite strains strongly supports the use of merozoite opsonization as a correlate of immunity for field studies and vaccine trials. These results demonstrate that conserved domains within merozoite antigens targeted by opsonization generate strain-transcending immune responses and represent promising vaccine candidates. PMID- 27185786 TI - Crude Preparations of Helicobacter pylori Outer Membrane Vesicles Induce Upregulation of Heme Oxygenase-1 via Activating Akt-Nrf2 and mTOR-IkappaB Kinase NF-kappaB Pathways in Dendritic Cells. AB - Helicobacter pylori sheds outer membrane vesicles (OMVs) that contain many surface elements of bacteria. Dendritic cells (DCs) play a major role in directing the nature of adaptive immune responses against H. pylori, and heme oxygenase-1 (HO-1) has been implicated in regulating function of DCs. In addition, HO-1 is important for adaptive immunity and the stress response. Although H. pylori-derived OMVs may contribute to the pathogenesis of H. pylori infection, responses of DCs to OMVs have not been elucidated. In the present study, we investigated the role of H. pylori-derived crude OMVs in modulating the expression of HO-1 in DCs. Exposure of DCs to crude H. pylori OMVs upregulated HO 1 expression. Crude OMVs obtained from a cagA-negative isogenic mutant strain induced less HO-1 expression than OMVs obtained from a wild-type strain. Crude H. pylori OMVs activated signals of transcription factors such as NF-kappaB, AP-1, and Nrf2. Suppression of NF-kappaB or Nrf2 resulted in significant attenuation of crude OMV-induced HO-1 expression. Crude OMVs increased the phosphorylation of Akt and downstream target molecules of mammalian target of rapamycin (mTOR), such as S6 kinase 1 (S6K1). Suppression of Akt resulted in inhibition of crude OMV induced Nrf2-dependent HO-1 expression. Furthermore, suppression of mTOR was associated with inhibition of IkappaB kinase (IKK), NF-kappaB, and HO-1 expression in crude OMV-exposed DCs. These results suggest that H. pylori-derived OMVs regulate HO-1 expression through two different pathways in DCs, Akt-Nrf2 and mTOR-IKK-NF-kappaB signaling. Following this induction, increased HO-1 expression in DCs may modulate inflammatory responses in H. pylori infection. PMID- 27185787 TI - Iron Limitation Triggers Early Egress by the Intracellular Bacterial Pathogen Legionella pneumophila. AB - Legionella pneumophila is an intracellular bacterial pathogen that replicates in alveolar macrophages, causing a severe form of pneumonia. Intracellular growth of the bacterium depends on its ability to sequester iron from the host cell. In the L. pneumophila strain 130b, one mechanism used to acquire this essential nutrient is the siderophore legiobactin. Iron-bound legiobactin is imported by the transport protein LbtU. Here, we describe the role of LbtP, a paralog of LbtU, in iron acquisition in the L. pneumophila strain Philadelphia-1. Similar to LbtU, LbtP is a siderophore transport protein and is required for robust growth under iron-limiting conditions. Despite their similar functions, however, LbtU and LbtP do not contribute equally to iron acquisition. The Philadelphia-1 strain lacking LbtP is more sensitive to iron deprivation in vitro Moreover, LbtP is important for L. pneumophila growth within macrophages while LbtU is dispensable. These results demonstrate that LbtP plays a dominant role over LbtU in iron acquisition. In contrast, loss of both LbtP and LbtU does not impair L. pneumophila growth in the amoebal host Acanthamoeba castellanii, demonstrating a host-specific requirement for the activities of these two transporters in iron acquisition. The growth defect of the DeltalbtP mutant in macrophages is not due to alterations in growth kinetics. Instead, the absence of LbtP limits L. pneumophila replication and causes bacteria to prematurely exit the host cell. These results demonstrate the existence of a preprogrammed exit strategy in response to iron limitation that allows L. pneumophila to abandon the host cell when nutrients are exhausted. PMID- 27185788 TI - Bile Acids Function Synergistically To Repress Invasion Gene Expression in Salmonella by Destabilizing the Invasion Regulator HilD. AB - Salmonella spp. are carried by and can acutely infect agricultural animals and humans. After ingestion, salmonellae traverse the upper digestive tract and initiate tissue invasion of the distal ileum, a virulence process carried out by the type III secretion system encoded within Salmonella pathogenicity island 1 (SPI-1). Salmonellae coordinate SPI-1 expression with anatomical location via environmental cues, one of which is bile, a complex digestive fluid that causes potent repression of SPI-1 genes. The individual components of bile responsible for SPI-1 repression have not been previously characterized, nor have the bacterial signaling processes that modulate their effects been determined. Here, we characterize the mechanism by which bile represses SPI-1 expression. Individual bile acids exhibit repressive activity on SPI-1-regulated genes that requires neither passive diffusion nor OmpF-mediated entry. By using genetic methods, the effects of bile and bile acids were shown to require the invasion gene transcriptional activator hilD and to function independently of known upstream signaling pathways. Protein analysis techniques showed that SPI-1 repression by bile acids is mediated by posttranslational destabilization of HilD. Finally, we found that bile acids function synergistically to achieve the overall repressive activity of bile. These studies demonstrate a common mechanism by which diverse environmental cues (e.g., certain short-chain fatty acids and bile acids) inhibit SPI-1 expression. These data provide information relevant to Salmonella pathogenesis during acute infection in the intestine and during chronic infection of the gallbladder and inform the basis for development of therapeutics to inhibit invasion as a means of repressing Salmonella pathogenicity. PMID- 27185789 TI - Use of Attenuated but Metabolically Competent Salmonella as a Probiotic To Prevent or Treat Salmonella Infection. AB - Salmonella enterica is among the most burdensome of foodborne disease agents. There are over 2,600 serovars that cause a range of disease manifestations ranging from enterocolitis to typhoid fever. While there are two vaccines in use in humans to protect against typhoid fever, there are none that prevent enterocolitis. If vaccines preventing enterocolitis were to be developed, they would likely protect against only one or a few serovars. In this report, we tested the hypothesis that probiotic organisms could compete for the preferred nutrient sources of Salmonella and thus prevent or treat infection. To this end, we added the fra locus, which encodes a utilization pathway for the Salmonella specific nutrient source fructose-asparagine (F-Asn), to the probiotic bacterium Escherichia coli Nissle 1917 (Nissle) to increase its ability to compete with Salmonella in mouse models. We also tested a metabolically competent, but avirulent, Salmonella enterica serovar Typhimurium mutant for its ability to compete with wild-type Salmonella The modified Nissle strain became more virulent and less able to protect against Salmonella in some instances. On the other hand, the modified Salmonella strain was safe and effective in preventing infection with wild-type Salmonella While we tested for efficacy only against Salmonella Typhimurium, the modified Salmonella strain may be able to compete metabolically with most, if not all, Salmonella serovars, representing a novel approach to control of this pathogen. PMID- 27185790 TI - Endothelial Cell Response to Fusobacterium nucleatum. AB - Vascular response is an essential aspect of an effective immune response to periodontal disease pathogens, as new blood vessel formation contributes to wound healing and inflammation. Gaining a greater understanding of the factors that affect vascular response may then contribute to future breakthroughs in dental medicine. In this study, we have characterized the endothelial cell response to the common bacterium Fusobacterium nucleatum, an important bridging species that facilitates the activity of late colonizers of the dental biofilm. Endothelial cells were infected with Fusobacterium nucleatum (strain 25586) for periods of 4, 12, 24, or 48 h. Cell proliferation and tube formation were analyzed, and expression of adhesion molecules (CD31 and CD34) and vascular endothelial growth factor (VEGF) receptors 1 and 2 was measured by fluorescence-activated cell sorter (FACS) analysis. Data indicate that F. nucleatum impaired endothelial cell proliferation and tube formation. The findings suggest that the modified endothelial cell response acts as a mechanism promoting the pathogenic progression of periodontal diseases and may potentially suggest the involvement of periodontopathogens in systemic diseases associated with periodontal inflammation. PMID- 27185792 TI - Visitors are using US website to search for high prescribing doctors. PMID- 27185793 TI - Changes in poisonings among adolescents in the UK between 1992 and 2012: a population based cohort study. AB - BACKGROUND: Poisonings are a common cause of morbidity and mortality among adolescents. Yet surveillance data indicating current incidence rates (IRs) and time trends are lacking, making policy development and service planning difficult. We utilised population based primary care data to estimate adolescent poisoning rates according to intent across the UK. METHODS: A cohort study of 1 311 021 adolescents aged 10-17 years, between 1992 and 2012, was conducted using routine primary care data from The Health Improvement Network. IRs and adjusted IRRs with 95% CIs were calculated for all poisonings, intentional, unintentional, unknown intent and alcohol related poisonings, by age, sex, calendar time and socioeconomic deprivation. RESULTS: Overall poisoning incidence increased by 27% from the period 1992-1996 to 2007-2012, with the largest increases in intentional poisonings among females aged 16-17 years (IR 391.4/100 000 person years (PY), CI 328.9 to 465.7 for age 17 years in 1992-1996; 767.0/100 000 PY, CI 719.5 to 817.7 in 2007-2012) and alcohol related poisonings in females aged 15-16 years (IR 65.7/100 000 PY, CI 43.3 to 99.8 rising to 130.0/100 000 PY, CI 110.0 to 150.0 for age 15 years). A strong socioeconomic gradient for all poisonings persisted over time, with higher rates among the more deprived (IRR 2.63, CI 2.41 to 2.88 for the most vs least deprived quintile in 2007-2012). CONCLUSIONS: Adolescent poisonings, especially intentional poisonings, have increased substantially over time and remain associated with health inequalities. Social and psychological support for adolescents should be targeted at more deprived communities, and child and adolescent mental health and alcohol support service provision should be commissioned to reflect the changing need. PMID- 27185791 TI - Clustered Intracellular Salmonella enterica Serovar Typhimurium Blocks Host Cell Cytokinesis. AB - Several bacterial pathogens and viruses interfere with the cell cycle of their host cells to enhance virulence. This is especially apparent in bacteria that colonize the gut epithelium, where inhibition of the cell cycle of infected cells enhances the intestinal colonization. We found that intracellular Salmonella enterica serovar Typhimurium induced the binucleation of a large proportion of epithelial cells by 14 h postinvasion and that the effect was dependent on an intact Salmonella pathogenicity island 2 (SPI-2) type 3 secretion system. The SPI 2 effectors SseF and SseG were required to induce binucleation. SseF and SseG are known to maintain microcolonies of Salmonella-containing vacuoles close to the microtubule organizing center of infected epithelial cells. During host cell division, these clustered microcolonies prevented the correct localization of members of the chromosomal passenger complex and mitotic kinesin-like protein 1 and consequently prevented cytokinesis. Tetraploidy, arising from a cytokinesis defect, is known to have a deleterious effect on subsequent cell divisions, resulting in either chromosomal instabilities or cell cycle arrest. In infected mice, proliferation of small intestinal epithelial cells was compromised in an SseF/SseG-dependent manner, suggesting that cytokinesis failure caused by S Typhimurium delays epithelial cell turnover in the intestine. PMID- 27185795 TI - Absence of Association between Polymorphisms in the RING E3 Ubiquitin Protein Ligase Gene and Ex Vivo Susceptibility to Conventional Antimalarial Drugs in Plasmodium falciparum Isolates from Dakar, Senegal. AB - The RING E3 ubiquitin protein ligase is crucial for facilitating the transfer of ubiquitin. The only polymorphism identified in the E3 ubiquitin protein ligase gene was the D113N mutation (62.5%) but was not significantly associated with the 50% inhibitory concentration (IC50) of conventional antimalarial drugs. However, some mutated isolates (D113N) present a trend of reduced susceptibility to piperaquine (P = 0.0938). To evaluate the association of D113N polymorphism with susceptibility to antimalarials, more isolates are necessary. PMID- 27185794 TI - Prospective Study of Plasmodium vivax Malaria Recurrence after Radical Treatment with a Chloroquine-Primaquine Standard Regimen in Turbo, Colombia. AB - Plasmodium vivax recurrences help maintain malaria transmission. They are caused by recrudescence, reinfection, or relapse, which are not easily differentiated. A longitudinal observational study took place in Turbo municipality, Colombia. Participants with uncomplicated P. vivax infection received supervised treatment concomitantly with 25 mg/kg chloroquine and 0.25 mg/kg/day primaquine for 14 days. Incidence of recurrence was assessed over 180 days. Samples were genotyped, and origins of recurrences were established. A total of 134 participants were enrolled between February 2012 and July 2013, and 87 were followed for 180 days, during which 29 recurrences were detected. The cumulative incidence of first recurrence was 24.1% (21/87) (95% confidence interval [CI], 14.6 to 33.7%), and 86% (18/21) of these events occurred between days 51 and 110. High genetic diversity of P. vivax strains was found, and 12.5% (16/128) of the infections were polyclonal. Among detected recurrences, 93.1% (27/29) of strains were genotyped as genetically identical to the strain from the previous infection episode, and 65.5% (19/29) of infections were classified as relapses. Our results indicate that there is a high incidence of P. vivax malaria recurrence after treatment in Turbo municipality, Colombia, and that a large majority of these episodes are likely relapses from the previous infection. We attribute this to the primaquine regimen currently used in Colombia, which may be insufficient to eliminate hypnozoites. PMID- 27185796 TI - Pharmacokinetics of Vancomycin in Elderly Patients Aged over 80 Years. AB - Since the 1950s, vancomycin has remained a reference treatment for severe infections caused by Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus Vancomycin is a nephrotoxic and ototoxic drug mainly eliminated through the kidneys. It has a large interindividual pharmacokinetic variability, which justifies monitoring its plasma concentrations in patients. This is especially important in patients aged over 80 years, who frequently have renal impairment. However, the pharmacokinetics of vancomycin in this population is very poorly described in the literature. The objective of this work was to propose a model able to predict the pharmacokinetics of vancomycin in very elderly people. First, a population pharmacokinetic model was carried out using the algorithm NPAG (nonparametric adaptive grid) on a database of 70 hospitalized patients aged over 80 years and treated with vancomycin. An external validation then was performed on 41 patients, and the predictive capabilities of the model were assessed. The model had two compartments and six parameters. Body weight and creatinine clearance significantly influenced vancomycin volume of distribution and body clearance, respectively. The means (+/- standard deviations) of vancomycin volume of distribution and clearance were 36.3 +/- 15.2 liter and 2.0 +/- 0.9 liter/h, respectively. In the validation group, the bias and precision were -0.75 mg/liter and 8.76 mg/liter for population predictions and -0.39 mg/liter and 2.68 mg/liter for individual predictions. In conclusion, a pharmacokinetic model of vancomycin in a very elderly population has been created and validated for predicting plasma concentrations of vancomycin. PMID- 27185797 TI - NDM-4- and NDM-5-Producing Klebsiella pneumoniae Coinfection in a 6-Month-Old Infant. PMID- 27185798 TI - Effect of Obesity on the Population Pharmacokinetics of Meropenem in Critically Ill Patients. AB - Severe pathophysiological changes in critical illness can lead to dramatically altered antimicrobial pharmacokinetics (PK). The additional effect of obesity on PK potentially increases the challenge for effective dosing. The aim of this prospective study was to describe the population PK of meropenem for a cohort of critically ill patients, including obese and morbidly obese patients. Critically ill patients prescribed meropenem were recruited into the following three body mass index (BMI) groups: nonobese (18.5 to 29.9 kg/m(2)), obese (30.0 to 39.9 kg/m(2)), and morbidly obese (>=40 kg/m(2)). Serial plasma samples were taken, and meropenem concentrations were determined using a validated chromatographic method. Population PK analysis and Monte Carlo dosing simulations were undertaken with Pmetrics. Nineteen critically ill patients with different BMI categories were enrolled. The patients' mean +/- standard deviation (SD) age, weight, and BMI were 49 +/- 15.9 years, 95 +/- 22.0 kg, and 33 +/- 7.0 kg/m(2), respectively. A two-compartment model described the data adequately. The mean +/- SD parameter estimates for the final covariate model were as follows: clearance (CL), 15.5 +/- 6.0 liters/h; volume of distribution in the central compartment (V1), 11.7 +/- 5.8 liters; intercompartmental clearance from the central compartment to the peripheral compartment, 25.6 +/- 35.1 liters h(-1); and intercompartmental clearance from the peripheral compartment to the central compartment, 8.32 +/- 12.24 liters h(-1) Higher creatinine clearance (CLCR) was associated with a lower probability of target attainment, with BMI having little effect. Although obesity was found to be associated with an increased V1, dose adjustment based on CLCR appears to be more important than patient BMI. PMID- 27185799 TI - Isavuconazole Population Pharmacokinetic Analysis Using Nonparametric Estimation in Patients with Invasive Fungal Disease (Results from the VITAL Study). AB - Isavuconazonium sulfate (Cresemba; Astellas Pharma Inc.), a water-soluble prodrug of the triazole antifungal agent isavuconazole, is available for the treatment of invasive aspergillosis (IA) and invasive mucormycosis. A population pharmacokinetic (PPK) model was constructed using nonparametric estimation to compare the pharmacokinetic (PK) behaviors of isavuconazole in patients treated in the phase 3 VITAL open-label clinical trial, which evaluated the efficacy and safety of the drug for treatment of renally impaired IA patients and patients with invasive fungal disease (IFD) caused by emerging molds, yeasts, and dimorphic fungi. Covariates examined were body mass index (BMI), weight, race, impact of estimated glomerular filtration rate (eGFR) on clearance (CL), and impact of weight on volume. PK parameters were compared based on IFD type and other patient characteristics. Simulations were performed to describe the MICs covered by the clinical dosing regimen. Concentrations (n = 458) from 136 patients were used to construct a 2-compartment model (first-order absorption compartment and central compartment). Weight-related covariates affected clearance, but eGFR did not. PK parameters and intersubject variability of CL were similar across different IFD groups and populations. Target attainment analyses demonstrated that the clinical dosing regimen would be sufficient for total drug area under the concentration-time curve (AUC)/MIC targets ranging from 50.5 for Aspergillus spp. (up to the CLSI MIC of 0.5 mg/liter) to 270 and 5,053 for Candida albicans (up to MICs of 0.125 and 0.004 mg/liter, respectively) and 312 for non-albicans Candida spp. (up to a MIC of 0.125 mg/liter). The estimations for Candida spp. were exploratory considering that no patients with Candida infections were included in the current analyses. (The VITAL trial is registered at ClinicalTrials.gov under number NCT00634049.). PMID- 27185800 TI - Mutations in pepQ Confer Low-Level Resistance to Bedaquiline and Clofazimine in Mycobacterium tuberculosis. AB - The novel ATP synthase inhibitor bedaquiline recently received accelerated approval for treatment of multidrug-resistant tuberculosis and is currently being studied as a component of novel treatment-shortening regimens for drug susceptible and multidrug-resistant tuberculosis. In a limited number of bedaquiline-treated patients reported to date, >=4-fold upward shifts in bedaquiline MIC during treatment have been attributed to non-target-based mutations in Rv0678 that putatively increase bedaquiline efflux through the MmpS5 MmpL5 pump. These mutations also confer low-level clofazimine resistance, presumably by a similar mechanism. Here, we describe a new non-target-based determinant of low-level bedaquiline and clofazimine cross-resistance in Mycobacterium tuberculosis: loss-of-function mutations in pepQ (Rv2535c), which corresponds to a putative Xaa-Pro aminopeptidase. pepQ mutants were selected in mice by treatment with clinically relevant doses of bedaquiline, with or without clofazimine, and were shown to have bedaquiline and clofazimine MICs 4 times higher than those for the parental H37Rv strain. Coincubation with efflux inhibitors verapamil and reserpine lowered bedaquiline MICs against both mutant and parent strains to a level below the MIC against H37Rv in the absence of efflux pump inhibitors. However, quantitative PCR (qPCR) revealed no significant differences in expression of Rv0678, mmpS5, or mmpL5 between mutant and parent strains. Complementation of a pepQ mutant with the wild-type gene restored susceptibility, indicating that loss of PepQ function is sufficient for reduced susceptibility both in vitro and in mice. Although the mechanism by which mutations in pepQ confer bedaquiline and clofazimine cross-resistance remains unclear, these results may have clinical implications and warrant further evaluation of clinical isolates with reduced susceptibility to either drug for mutations in this gene. PMID- 27185801 TI - Discovery of a Broad-Spectrum Antiviral Compound That Inhibits Pyrimidine Biosynthesis and Establishes a Type 1 Interferon-Independent Antiviral State. AB - Viral emergence and reemergence underscore the importance of developing efficacious, broad-spectrum antivirals. Here, we report the discovery of tetrahydrobenzothiazole-based compound 1, a novel, broad-spectrum antiviral lead that was optimized from a hit compound derived from a cytopathic effect (CPE) based antiviral screen using Venezuelan equine encephalitis virus. Compound 1 showed antiviral activity against a broad range of RNA viruses, including alphaviruses, flaviviruses, influenza virus, and ebolavirus. Mechanism-of-action studies with metabolomics and molecular approaches revealed that the compound inhibits host pyrimidine synthesis and establishes an antiviral state by inducing a variety of interferon-stimulated genes (ISGs). Notably, the induction of the ISGs by compound 1 was independent of the production of type 1 interferons. The antiviral activity of compound 1 was cell type dependent with a robust effect observed in human cell lines and no observed antiviral effect in mouse cell lines. Herein, we disclose tetrahydrobenzothiazole compound 1 as a novel lead for the development of a broad-spectrum, antiviral therapeutic and as a molecular probe to study the mechanism of the induction of ISGs that are independent of type 1 interferons. PMID- 27185804 TI - Antimicrobial Susceptibility of Neisseria gonorrhoeae in Bangladesh (2014 Update). PMID- 27185802 TI - In Vitro Emergence of High Persistence upon Periodic Aminoglycoside Challenge in the ESKAPE Pathogens. AB - Health care-associated infections present a major threat to modern medical care. Six worrisome nosocomial pathogens-Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.-are collectively referred to as the "ESKAPE bugs." They are notorious for extensive multidrug resistance, yet persistence, or the phenotypic tolerance displayed by a variant subpopulation, remains underappreciated in these pathogens. Importantly, persistence can prevent eradication of antibiotic sensitive bacterial populations and is thought to act as a catalyst for the development of genetic resistance. Concentration- and time-dependent aminoglycoside killing experiments were used to investigate persistence in the ESKAPE pathogens. Additionally, a recently developed method for the experimental evolution of persistence was employed to investigate adaptation to high-dose, extended-interval aminoglycoside therapy in vitro We show that ESKAPE pathogens exhibit biphasic killing kinetics, indicative of persister formation. In vitro cycling between aminoglycoside killing and persister cell regrowth, evocative of clinical high-dose extended-interval therapy, caused a 37- to 213-fold increase in persistence without the emergence of resistance. Increased persistence also manifested in biofilms and provided cross-tolerance to different clinically important antibiotics. Together, our results highlight a possible drawback of intermittent, high-dose antibiotic therapy and suggest that clinical diagnostics might benefit from taking into account persistence. PMID- 27185803 TI - Antiviral Activity of Favipiravir (T-705) against a Broad Range of Paramyxoviruses In Vitro and against Human Metapneumovirus in Hamsters. AB - The clinical impact of infections with respiratory viruses belonging to the family Paramyxoviridae argues for the development of antiviral therapies with broad-spectrum activity. Favipiravir (T-705) has demonstrated potent antiviral activity against multiple RNA virus families and is presently in clinical evaluation for the treatment of influenza. Here we demonstrate in vitro activity of T-705 against the paramyxoviruses human metapneumovirus (HMPV), respiratory syncytial virus, human parainfluenza virus, measles virus, Newcastle disease virus, and avian metapneumovirus. In addition, we demonstrate activity against HMPV in hamsters. T-705 treatment inhibited replication of all paramyxoviruses tested in vitro, with 90% effective concentration (EC90) values of 8 to 40 MUM. Treatment of HMPV-challenged hamsters with T-705 at 200 mg/kg of body weight/day resulted in 100% protection from infection of the lungs. In all treated and challenged animals, viral RNA remained detectable in the respiratory tract. The observation that T-705 treatment had a significant effect on infectious viral titers, with a limited effect on viral genome titers, is in agreement with its proposed mode of action of viral mutagenesis. However, next-generation sequencing of viral genomes isolated from treated and challenged hamsters did not reveal (hyper)mutation. Polymerase activity assays revealed a specific effect of T-705 on the activity of the HMPV polymerase. With the reported antiviral activity of T 705 against a broad range of RNA virus families, this small molecule is a promising broad-range antiviral drug candidate for limiting the viral burden of paramyxoviruses and for evaluation for treatment of infections with (re)emerging viruses, such as the henipaviruses. PMID- 27185805 TI - Isolation and Characterization of Escherichia coli Sequence Type 131 and Other Antimicrobial-Resistant Gram-Negative Bacilli from Clinical Stool Samples from Veterans. AB - Emerging multidrug-resistant (MDR) Gram-negative bacilli (GNB), including Escherichia coli sequence type 131 (ST131) and its resistance-associated H30 subclone, constitute an ever-growing public health threat. Their reservoirs and transmission pathways are incompletely defined. To assess diarrheal stools as a potential reservoir for ST131-H30 and other MDR GNB, we cultured 100 clinical stool samples from a Veterans Affairs Medical Center clinical laboratory (October to December 2011) for fluoroquinolone- and extended-spectrum cephalosporin (ESC) resistant E. coli and other GNB, plus total E. coli We then characterized selected resistant and susceptible E. coli isolates by clonal group, phylogenetic group, virulence genotype, and pulsotype and screened all isolates for antimicrobial resistance. Overall, 79 of 100 stool samples yielded GNB (52 E. coli; 48 other GNB). Fifteen samples yielded fluoroquinolone-resistant E. coli (10 were ST131, of which 9 were H30), 6 yielded ESC-resistant E. coli (2 were ST131, both non-H30), and 31 yielded susceptible E. coli (1 was ST131, non-H30), for 13 total ST131-positive samples. Fourteen non-E. coli GNB were ESC resistant, and three were fluoroquinolone resistant. Regardless of species, almost half (46%) of the fluoroquinolone-resistant and/or ESC-resistant non-E. coli GNB were resistant to at least three drug classes. Fecal ST131 isolates closely resembled reference clinical ST131 isolates according to virulence genotypes and pulsed field gel electrophoresis (PFGE) profiles. Thus, a substantial minority (30%) of veterans with diarrhea who undergo stool testing excrete antibiotic-resistant GNB, including E. coli ST131. Consequently, diarrhea may pose transmission risks for more than just diarrheal pathogens and may help disseminate clinically relevant ST131 strains and other MDR GNB within hospitals and the community. PMID- 27185806 TI - Immunoassay Analysis of Kanamycin in Serum Using the Tobramycin Kit. AB - Kanamycin is one of the aminoglycosides used in the treatment of multidrug resistant tuberculosis. Blood concentrations of kanamycin are predictive for the treatment efficacy and the occurrence of side effects, and dose adjustments can be needed to optimize therapy. However, an immunoassay method for the quantification of kanamycin is not commercially available. We modified the existing tobramycin immunoassay to analyze kanamycin. This modified method was tested in a concentration range of 0.3 to 80.0 mg/liter for inaccuracy and imprecision. In addition, the analytical results of the immunoassay method were compared to those obtained by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) analytical method using Passing and Bablok regression. Within-day imprecision varied from 2.3 to 13.3%, and between-day imprecision ranged from 0.0 to 11.3%. The inaccuracy ranged from -5.2 to 7.6%. No significant cross reactivity with other antimicrobials and antiviral agents was observed. The results of the modified immunoassay method were comparable with the LC-MS/MS analytical outcome. This new immunoassay method enables laboratories to perform therapeutic drug monitoring of kanamycin without the need for complex and expensive LC-MS/MS equipment. PMID- 27185808 TI - Pharmacokinetics of Tedizolid in Morbidly Obese and Covariate-Matched Nonobese Adults. AB - Tedizolid is a novel oxazolidinone antimicrobial administered in its prodrug form, tedizolid phosphate, as a fixed once-daily dose. The pharmacokinetics of tedizolid has been studied in a relatively small proportion of morbidly obese (body mass index [BMI] of >=40 kg/m(2)) adults through population analyses with sparse sampling. The current study compared the intensively sampled plasma pharmacokinetics of tedizolid phosphate and tedizolid in 9 morbidly obese and 9 age-, sex-, and ideal body weight-matched nonobese (BMI, 18.5 to 29.9 kg/m(2)) healthy adult (18 to 50 years of age) volunteers after administration of a single intravenous dose of tedizolid phosphate. The median (range) weights were 72.6 kg (58.9 to 89.5 kg) and 117 kg (102 to 176 kg) for the mostly female (77.8%) nonobese and morbidly obese adults, respectively. Tedizolid phosphate concentrations were below the limit of quantitation in a majority of subjects after the 2-h time point. The tedizolid median (range) maximum concentration of drug in plasma (Cmax) and area under the concentration-time curve from 0 h to infinity (AUC0-infinity) were 2.38 (1.28 to 3.99) mg/liter and 26.3 (18.4 to 43.2) h . mg/liter, respectively, for morbidly obese subjects, and these were nonsignificantly different (P >= 0.214) from the values for nonobese subjects. Similarly, the volumes of distribution (Vz) (P = 0.110) and clearance (CL) values (P = 0.214) were comparable between groups. Nearly identical (P = 0.953) median tedizolid half-lives of approximately 12 h were observed for both groups. Tedizolid Vz and CL scaled with body weight, but not proportionately. The small and nonsignificant differences in tedizolid AUC0-infinity values between morbidly obese and nonobese subjects suggest that dose modification is not necessary for morbidly obese adults. (This study has been registered at ClinicalTrials.gov under number NCT02342418.). PMID- 27185807 TI - In Vivo Rectal Mucosal Barrier Function Imaging in a Large-Animal Model by Using Confocal Endomicroscopy: Implications for Injury Assessment and Use in HIV Prevention Studies. AB - Injury occurring on the surface of the rectal mucosal lining that causes defects in barrier function may result in increased risk for transmission of infection by HIV and other pathogens. Such injury could occur from microbicidal or other topical agents, mechanical trauma during consensual or nonconsensual intercourse, or inflammatory conditions. Tools for evaluation of rectal mucosal barrier function for assessing the mucosa under these conditions are lacking, particularly those that can provide in vivo structural and functional barrier integrity assessment and are adaptable to longitudinal imaging. We investigated confocal endomicroscopy (CE) as a means for in vivo imaging of the rectal epithelial barrier in the ovine model following spatially confined injury to the surface at a controlled site using a topical application of the microbicide test agent benzalkonium chloride. Topical and intravenous (i.v.) fluorescent probes were used with CE to provide subcellular resolution imaging of the mucosal surface and assessment of barrier function loss. A 3-point CE grading system based on cellular structure integrity and leakage of dye through the mucosa showed significant differences in score between untreated (1.19 +/- 0.53) and treated (2.55 +/- 0.75) tissue (P < 0.0001). Histological grading confirmed findings of barrier compromise. The results indicate that CE is an effective means for detecting epithelial injury and barrier loss following localized trauma in a large-animal model. CE is promising for real-time rectal mucosal evaluation after injury or trauma or topical application of emerging biomedical prevention strategies designed to combat HIV. PMID- 27185809 TI - Facility distance and child mortality: a multi-country study of health facility access, service utilization, and child health outcomes. AB - Background: Access to health facilities remains limited in many resource-poor settings, and women and their children often have to travel far to seek care. However, data on distance are scarce, and it is unclear whether distance is associated with worse child health outcomes. We estimate the relationships between distance to facility, service utilization and child mortality in low- and middle-income countries. Methods: Population-representative data are pooled from 29 demographic and health surveys across 21 low- and middle-income countries. Multivariable logistic models and meta-analysis regressions are used to estimate associations between facility distance, child mortality, and health care utilization in the pooled sample as well as for each survey. Results: Compared with children who live within 1 km of a facility, children living within 2 km, 3 km, and 5 km of a facility have a 7.7% [95% confidence interval (CI): 0.927 - 1.251], 16.3% (95% CI: 1.020 - 1.327) and 25% (95% CI: 1.087 - 1.439) higher odds of neonatal mortality, respectively; children living farther than 10 km have a 26.6% (95% CI: 1.108 - 1.445) higher odds of neonatal mortality. Women living farther than 10 km from a facility have a 55.3% lower odds of in-facility delivery compared with women who live within 1 km [odds ratio (OR): 0.447; 95% CI: 0.394 - 0.508]. Conclusions: Even relatively small distances from health facilities are associated with substantial mortality penalties for children. Policies that reduce travel distances and travel times are likely to increase utilization of health services and reduce neonatal mortality. PMID- 27185811 TI - Profile: The Rusinga Health and Demographic Surveillance System, Western Kenya. AB - The health and demographic surveillance system on Rusinga Island, Western Kenya, was initiated in 2012 to facilitate a malaria intervention trial: the SolarMal project. The project aims to eliminate malaria from Rusinga Island using the nationwide adopted strategy for malaria control (insecticide-treated bed nets and case management) augmented with mass trapping of anopheline mosquitoes. The main purpose of the health and demographic surveillance is to measure the effectiveness of the trial on clinical malaria incidence, and to monitor demographic, environmental and malaria-related data variables. At the end of 2014, the 44 km(2) island had a population of approximately 25 000 individuals living in 8746 residential structures. Three times per year, all individuals are followed up and surveyed for clinical malaria. Following each round of surveillance, a randomly selected cross-section of the population is subject to a rapid diagnostic test to measure malaria. Additionally, extensive monitoring of malaria vectors is performed. Data collection and management are conducted using the OpenHDS platform, with tablet computers and applications with advanced software connected to a centralized database. Besides the general demographic information, other health-related data are collected which can be used to facilitate a range of other studies within and outside the current project. Access to the core dataset can be obtained on request from the authors. PMID- 27185812 TI - National findings regarding health IT use and participation in health care delivery reform programs among office-based physicians. AB - OBJECTIVE: Our objective was to characterize physicians' participation in delivery and payment reform programs over time and describe how participants in these programs were using health information technology (IT) to coordinate care, engage patients, manage patient populations, and improve quality. MATERIALS AND METHODS: A nationally representative cohort of physicians was surveyed in 2012 (unweighted N = 2567) and 2013 (unweighted N = 2399). Regression analyses used those survey responses to identify associations between health IT use and participation in and attrition from patient-centered medical homes (PCMHs), accountable care organizations (ACOs), and pay-for-performance programs (P4Ps). RESULTS: In 2013, 45% of physicians participated in PCMHs, ACOs, or P4Ps. While participation in each program increased (P < .05) between 2012 and 2013, program attrition ranged from 31-40%. Health IT use was associated with greater program participation (RR = 1.07-1.16). PCMH, ACO, and P4P participants were more likely than nonparticipants to perform quality improvement and patient engagement activities electronically (RR = 1.09-1.14); only ACO participants were more likely to share information electronically (RR = 1.07-1.09). DISCUSSION: Participation in delivery and payment reform programs increased between 2012 and 2013. Participating physicians were more likely to use health IT. There was significant attrition from and switching between PCMHs, ACOs, and P4Ps. CONCLUSION: This work provides the basis for understanding physician participation in and attrition from delivery and payment reform programs, as well as how health IT was used to support those programs. Understanding health IT use by program participants may help to identify factors enabling a smooth transition to alternative payment models. PMID- 27185814 TI - Concussions and suicide. PMID- 27185815 TI - Concussions and suicide. PMID- 27185810 TI - Variation in worldwide incidence of amyotrophic lateral sclerosis: a meta analysis. AB - Background: To assess the worldwide variation of amyotrophic lateral sclerosis (ALS) incidence, we performed a systematic review and meta-analysis of population based data published to date. Methods: We reviewed Medline and Embase up to June 2015 and included all population-based studies of newly diagnosed ALS cases, using multiple sources for case ascertainment. ALS crude and standardized incidence (on age and sex using the US 2010 population) were calculated. Random effect meta-analysis and meta-regression were performed using the subcontinent as the main study level covariate. Sources of heterogeneity related to the characteristics of the study population and the study methodology were investigated. Results: Among 3216 records, 44 studies were selected, covering 45 geographical areas in 11 sub-continents. A total of 13 146 ALS cases and 825 million person-years of follow-up (PYFU) were co-nsidered. The overall pooled worldwide crude ALS incidence was at 1.75 (1.55-1.96)/100 000 PYFU; 1.68 (1.50 1.85)/100 000 PYFU after standardization. Heterogeneity was identified in ALS standardized incidence between North Europe [1.89 (1.46-2.32)/100 000 PYFU] and East Asia [0.83 (0.42-1.24)/100 000 PYFU, China and Japan P = 0.001] or South Asia [0.73 (0.58-0.89)/100 000/PYFU Iran, P = 0.02]. Conversely, homogeneous rates have been reported in populations from Europe, North America and New Zealand [pooled ALS standardized incidence of 1.81 (1.66-1.97)/100 000 PYFU for those areas]. Conclusion: This review confirms a heterogeneous distribution worldwide of ALS, and sets the scene to sustain a collaborative study involving a wide international consortium to investigate the link between ancestry, environment and ALS incidence. PMID- 27185816 TI - Carboxy-THC in Washed Hair: Still the Reliable Indicator of Marijuana Ingestion. AB - The presence of the metabolite 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (C THC) in hair is generally accepted as the definitive proof of delta-9 tetrahydrocannabinol (THC) ingestion. During hair analysis, the removal of any potential C-THC external contamination that could result from marijuana smoke or close personal contact via a wash procedure is critical. Here, we performed a series of experiments to demonstrate that C-THC is the reliable indicator of marijuana ingestion when paired with the correct washing procedure to remove potential external contamination. PMID- 27185818 TI - Determination of Dextromethorphan in Oral Fluid by LC-MS-MS. AB - Dextromethorphan (DXM) is an antitussive drug found in commonly used nonprescription cold and cough medications. At low doses, DXM is a safe drug that does not produce adverse reactions. However, abuse of DXM has been reported among adolescents and young adults using the drug at higher doses. DXM is not a scheduled drug in the USA, and the primary reason for its abuse is the ease of availability. DXM is available to purchase in the form of over-the-counter cough medications, such as Robitussin((r)) and Coricidin((r)), or it can be purchased over the Internet in the form of a powder. In this research work, we developed an LC-MS-MS method that can quantify DXM and dextrorphan (DXO) in oral fluid in a high-throughput toxicology laboratory setting. The developed method was validated according to the Scientific Working Group for Forensic Toxicology guidelines. The linear dynamic range was 5-100 ng/mL with a lowest limit of quantitation (LLOQ) of 5.0 ng/mL for DXM and DXO. Overall, the results of the accuracy and the precision values were within the acceptance criteria for both drugs. In addition, selectivity, matrix effect and recovery were calculated for the LC-MS-MS method. Authentic samples (n = 59) were tested to evaluate the applicability of the method. Thirty samples were found to be positive for DXM and DXO and two samples were found to be positive for DXM only. PMID- 27185817 TI - Simultaneous Analysis of Cannabinoid and Synthetic Cannabinoids in Dietary Supplements Using UPLC with UV and UPLC-MS-MS. AB - The primary purpose of this study was to develop and validate a method based on UPLC with UV and UPLC-MS-MS for the simultaneous analysis of different cannabinoids and synthetic cannabinoids in food as well as in herbal and dietary supplements. The limits of detection and quantitation of the method ranged from 0.1 to 0.3 and 0.3 to 0.9 MUg/mL by UPLC with UV, respectively. The coefficient of determination was >0.999; the intra- and interday precision of the method were 0.1-3.7 and 0.9-4.1%, respectively. The intra- and interday accuracy were 94.8 103.1 and 98.3-100.9%, respectively. The mean recoveries of nine cannabinoids obtained from tablet samples ranged from 81.1 to 105.4%. The mean extraction recoveries of nine target cannabinoids obtained from various types of samples (tablets, capsules, powders, liquids, cookies and candies) ranged from 82.26 to 112.40%. The relative standard deviation (RSD) of the stability of the prepared sample solutions was <1.80%. Identification and quantification of the nine cannabinoids were accomplished by ion spray UPLC-MS-MS using multiple reaction monitoring. The UPLC-MS-MS method was validated for linearity (R(2) > 0.99); the precision was 0.1-4.0% (intraday) and 0.1-2.8% (interday), and the accuracy was 98.0-103.5% (intraday) and 97.1-103.2% (interday). The mean extraction recoveries of six types of samples were 82.2-114.5% and the RSD of stability was <6.54%, complying with the established international guidelines. The results indicated that the method can be used for rapid and accurate screening of cannabinoids present in food. PMID- 27185819 TI - Evaluation of Postmortem Drug Concentrations in Bile Compared with Blood and Urine in Forensic Autopsy Cases. AB - For drug screening and pharmaco-/toxicokinetic analysis, bile as a major drug excretion route in addition to urine may be used in forensic autopsy cases; however, there are limited published data on correlations between bile and blood or urine drug concentrations. The present study retrospectively investigated drug concentrations in bile, compared with blood and urine concentrations, reviewing forensic autopsy cases during 6 years (January 2009-December 2014). Drugs were analyzed using automated gas chromatography-mass spectrometry following solid liquid phase extraction. Compared with peripheral blood concentrations, bile concentrations were higher for most drugs; however, caffeine concentrations were similar. Bile concentrations were mostly lower than urine concentrations for amphetamines, caffeine and methylephedrine, but were usually similar to or higher for other drugs. Significant correlations were detected between bile and peripheral blood concentrations for amphetamines, several cold remedies, phenobarbital, phenothiazine derivatives and diazepam, as well as between bile and urine concentrations for amphetamines, caffeine, diphenhydramine, phenobarbital and promethazine derivatives. These findings suggest that bile can provide supplemental data useful in routine forensic toxicology, for the spectrum of drugs mentioned above, as well as for investigating pharmaco-/toxicokinetics and postmortem redistribution when analyzed in combination with drug concentrations at other sites. PMID- 27185820 TI - Ultrafast Screening of Synthetic Cannabinoids and Synthetic Cathinones in Urine by RapidFire-Tandem Mass Spectrometry. AB - Screening for emerging drugs of abuse, specifically synthetic cathinones and synthetic cannabinoids, is difficult for high-throughput laboratories as immunoassay kits are often unavailable. Consequently, most laboratories employ liquid chromatography-tandem mass spectrometry (LC-MS-MS) screening, which can be complex and time consuming as these techniques may require involved sample preparation and lengthy analysis times. The increasing demand for novel psychoactive substance testing necessitates alternative screening methods that are sensitive, fast and versatile. The RapidFire tandem mass spectrometry system (RF-MS-MS) provides a rapid and highly specific screen for these emerging drugs of abuse with minimal sample preparation and an instrumental analysis time of <14 s per sample. Presented here are two RF-MS-MS screening methods used to analyze 28 emerging drugs of abuse, 14 synthetic cannabinoids and 14 synthetic cathinones, in urine with run times of 9 and 12.6 s, respectively. Sample preparation and hydrolysis were performed in a 96-well plate with one multiple reaction monitoring transition used for the identification of each compound. Eighteen thousand urine specimens were screened by liquid-liquid extraction followed by LC-MS-MS analysis, and the results were compared with those obtained using the RF-MS-MS screening method. The analytical data illustrate the advantages of the RF-MS-MS methods. PMID- 27185821 TI - Twenty-One Cases Involving Alpha-Pyrrolidinovalerophenone (alpha-PVP). AB - Twenty-one cases involving alpha-pyrrolidinovalerophenone (alpha-PVP) were submitted between 2012 and 2015 to the Western Department of Forensic Science Laboratory. Eighteen suspected impaired driving cases were determined to have alpha-PVP concentrations <0.005-0.09 mg/L. Three fatalities during this period were determined to have alpha-PVP concentrations ranging from 0.03 to >20 mg/L. Human use of synthetic cathinones like alpha-PVP has been reported to induce psychological effects such as delusions, paranoia, hallucinations and deleterious cardiovascular effects. Quantitation was performed using a liquid-liquid extraction with detection by liquid chromatography triple quadrupole mass spectrometry using electrospray ionization in a multiple reaction monitoring mode. The reported behaviors in the 18 suspected impaired driving cases ranged from central nervous system depression to eluding officers in a high speed chase. The mean and median DUID alpha-PVP concentrations were both 0.030 mg/L. The alpha PVP concentrations in the three fatalities were determined to be 0.033, 0.054 and present >20 mg/L. In 18 DUID cases, only 4 cases reported side effects consistent with synthetic cathinones. Two of the three fatalities indicated histories of bath salt and/or recreational drug use. At this time, no correlation can be determined between side effects and alpha-PVP concentrations. PMID- 27185826 TI - Pseudomonas aeruginosa AmrZ Binds to Four Sites in the algD Promoter, Inducing DNA-AmrZ Complex Formation and Transcriptional Activation. AB - During late stages of cystic fibrosis pulmonary infections, Pseudomonas aeruginosa often overproduces the exopolysaccharide alginate, protecting the bacterial community from host immunity and antimicrobials. The transcription of the alginate biosynthesis operon is under tight control by a number of factors, including AmrZ, the focus of this study. Interestingly, multiple transcription factors interact with the far-upstream region of this promoter (PalgD), in which one AmrZ binding site has been identified previously. The mechanisms of AmrZ binding and subsequent activation remain unclear and require more-detailed investigation. In this study, in-depth examinations elucidated four AmrZ binding sites, and their disruption eliminated AmrZ binding and promoter activation. Furthermore, our in vitro fluorescence resonance energy transfer experiments suggest that AmrZ holds together multiple binding sites in PalgD and thereafter induces the formation of higher-order DNA-AmrZ complexes. To determine the importance of interactions between those AmrZ oligomers in the cell, a DNA phasing experiment was performed. PalgD transcription was significantly impaired when the relative phase between AmrZ binding sites was reversed (5 bp), while a full-DNA-turn insertion (10 bp) restored promoter activity. Taken together, the investigations presented here provide a deeper mechanistic understanding of AmrZ mediated binding to PalgD IMPORTANCE: Overproduction of the exopolysaccharide alginate provides protection to Pseudomonas aeruginosa against antimicrobial treatments and is associated with chronic P. aeruginosa infections in the lungs of cystic fibrosis patients. In this study, we combined a variety of microbiological, genetic, biochemical, and biophysical approaches to investigate the activation of the alginate biosynthesis operon promoter by a key transcription factor named AmrZ. This study has provided important new information on the mechanism of activation of this extremely complex promoter. PMID- 27185825 TI - F420H2 Is Required for Phthiocerol Dimycocerosate Synthesis in Mycobacteria. AB - Phthiocerol dimycocerosates (PDIM) are a group of cell surface-associated apolar lipids of Mycobacterium tuberculosis and closely related mycobacteria, such as Mycobacterium bovis and Mycobacterium leprae A characteristic methoxy group of these lipids is generated from the methylation of a hydroxyl group of the direct precursors, the phthiotriols. The precursors arise from the reduction of phthiodiolones, the keto intermediates, by a ketoreductase. The putative phthiodiolone ketoreductase (PKR) is encoded by Rv2951c in M. tuberculosis and BCG_2972c in M. bovis BCG, and these open reading frames (ORFs) encode identical amino acid sequences. We investigated the cofactor requirement of the BCG_2972c protein. A comparative analysis based on the crystallographic structures of similar enzymes identified structural elements for binding of coenzyme F420 and hydrophobic phthiodiolones in PKR. Coenzyme F420 is a deazaflavin coenzyme that serves several key functions in pathogenic and nonpathogenic mycobacteria. We found that an M. bovis BCG mutant lacking F420-dependent glucose-6-phosphate dehydrogenase (Fgd), which generates F420H2 (glucose-6-phosphate + F420 -> 6 phosphogluconate + F420H2), was devoid of phthiocerols and accumulated phthiodiolones. When the mutant was provided with F420H2, a broken-cell slurry of the mutant converted accumulated phthiodiolones to phthiocerols; F420H2 was generated in situ from F420 and glucose-6-phosphate by the action of Fgd. Thus, the reaction mixture was competent in reducing phthiodiolones to phthiotriols (phthiodiolones + F420H2 -> phthiotriols + F420), which were then methylated to phthiocerols. These results established the mycobacterial phthiodiolone ketoreductase as an F420H2-dependent enzyme (fPKR). A phylogenetic analysis of close homologs of fPKR revealed potential F420-dependent lipid-modifying enzymes in a broad range of mycobacteria. IMPORTANCE: Mycobacterium tuberculosis is the causative agent of tuberculosis, and phthiocerol dimycocerosates (PDIM) protect this pathogen from the early innate immune response of an infected host. Thus, the PDIM synthesis system is a potential target for the development of effective treatments for tuberculosis. The current study shows that a PDIM synthesis enzyme is dependent on the coenzyme F420 F420 is universally present in mycobacteria and absent in humans. This finding expands the number of experimentally validated F420-dependent enzymes in M. tuberculosis to six, each of which helps the pathogen to evade killing by the host immune system, and one of which activates an antituberculosis drug, PA-824. This work also has relevance to leprosy, since similar waxy lipids are found in Mycobacterium leprae. PMID- 27185827 TI - Amyloid Structures as Biofilm Matrix Scaffolds. AB - Recent insights into bacterial biofilm matrix structures have induced a paradigm shift toward the recognition of amyloid fibers as common building block structures that confer stability to the exopolysaccharide matrix. Here we describe the functional amyloid systems related to biofilm matrix formation in both Gram-negative and Gram-positive bacteria and recent knowledge regarding the interaction of amyloids with other biofilm matrix components such as extracellular DNA (eDNA) and the host immune system. In addition, we summarize the efforts to identify compounds that target amyloid fibers for therapeutic purposes and recent developments that take advantage of the amyloid structure to engineer amyloid fibers of bacterial biofilm matrices for biotechnological applications. PMID- 27185828 TI - Regulatory Requirements for Staphylococcus aureus Nitric Oxide Resistance. AB - The ability of Staphylococcus aureus to resist host innate immunity augments the severity and pervasiveness of its pathogenesis. Nitric oxide (NO) is an innate immune radical that is critical for the efficient clearance of a wide range of microbial pathogens. Exposure of microbes to NO typically results in growth inhibition and induction of stress regulons. S. aureus, however, induces a metabolic state in response to NO that allows for continued replication and precludes stress regulon induction. The regulatory factors mediating this distinctive response remain largely undefined. Here, we employ a targeted transposon screen and transcriptomics to identify and characterize five regulons essential for NO resistance in S. aureus: three virulence regulons not formerly associated with NO resistance, SarA, CodY, and Rot, as well as two regulons with established roles, Fur and SrrAB. We provide new insights into the contributions of Fur and SrrAB during NO stress and show that the S. aureus DeltasarA mutant, the most sensitive of the newly identified mutants, exhibits metabolic dysfunction and widespread transcriptional dysregulation following NO exposure. Altogether, our results broadly characterize the regulatory requirements for NO resistance in S. aureus and suggest an intriguing overlap between the regulation of NO resistance and virulence in this well-adapted human pathogen. IMPORTANCE: The prolific human pathogen Staphylococcus aureus is uniquely capable of resisting the antimicrobial radical nitric oxide (NO), a crucial component of the innate immune response. However, a complete understanding of how S. aureus regulates an effective response to NO is lacking. Here, we implicate three central virulence regulators, SarA, CodY, and Rot, as major players in the S. aureus NO response. Additionally, we elaborate on the contribution of two regulators, SrrAB and Fur, already known to play a crucial role in S. aureus NO resistance. Our study sheds light on a unique facet of S. aureus pathogenicity and demonstrates that the transcriptional response of S. aureus to NO is highly pleiotropic and intrinsically tied to metabolism and virulence regulation. PMID- 27185830 TI - Implementing Intellectual Property of Pharmaceuticals in Middle-Income Countries: A Case Study of Patent Regulation in Brazil. AB - The protection of pharmaceutical intellectual property (IP) rights is one of the most controversial debates in contemporary public health as countries have to balance incentives for drug development with the necessity of providing life saving drugs. Compliance with IP protections is mandatory for members of the World Trade Organization (WTO). However, because of the costs associated with IP implementation we should expect late and/or poor implementation in middle-income countries. Surprisingly, this was not the case in Brazil. The country not only just fully implemented the WTO's requirement but declined the grace period granted for countries to adapt and included extra IP protections, going against a coalition of local industrialists and activists. Notwithstanding, as the consequences of IP regulations unfolds, Brazil also promoted new alliances that tailored and adjusted the regulations toward public health. We demonstrate that arguments of foreign pressure and lobbying are exaggerated and call attention to domestic shifts, long-term processes of regulatory decision, and political dynamics happening at the local level. By analyzing the case of Brazil, we provide a nuanced contribution to the discussion of IP implementation in middle income countries and call attention to new models of government-society interactions in regulatory policy. PMID- 27185829 TI - Identification of a Lipoteichoic Acid Glycosyltransferase Enzyme Reveals that GW Domain-Containing Proteins Can Be Retained in the Cell Wall of Listeria monocytogenes in the Absence of Lipoteichoic Acid or Its Modifications. AB - Listeria monocytogenes is a foodborne Gram-positive bacterial pathogen, and many of its virulence factors are either secreted proteins or proteins covalently or noncovalently attached to the cell wall. Previous work has indicated that noncovalently attached proteins with GW (glycine-tryptophan) domains are retained in the cell wall by binding to the cell wall polymer lipoteichoic acid (LTA). LTA is a glycerol phosphate polymer, which is modified in L. monocytogenes with galactose and d-alanine residues. We identified Lmo0933 as the cytoplasmic glycosyltransferase required for the LTA glycosylation process and renamed the protein GtlA, for glycosyltransferase LTA A Using L. monocytogenes mutants lacking galactose or d-alanine modifications or the complete LTA polymer, we show that GW domain proteins are retained within the cell wall, indicating that other cell wall polymers are involved in the retention of GW domain proteins. Further experiments revealed peptidoglycan as the binding receptor as a purified GW domain fusion protein can bind to L. monocytogenes cells lacking wall teichoic acid (WTA) as well as purified peptidoglycan derived from a wild-type or WTA negative strain. With this, we not only identify the first enzyme involved in the LTA glycosylation process, but we also provide new insight into the binding mechanism of noncovalently attached cell wall proteins. IMPORTANCE: Over the past 20 years, a large number of bacterial genome sequences have become available. Computational approaches are used for the genome annotation and identification of genes and encoded proteins. However, the function of many proteins is still unknown and often cannot be predicted bioinformatically. Here, we show that the previously uncharacterized Listeria monocytogenes gene lmo0933 likely codes for a glycosyltransferase required for the decoration of the cell wall polymer lipoteichoic acid (LTA) with galactose residues. Using L. monocytogenes mutants lacking LTA modifications or the complete polymer, we show that specific cell wall proteins, often associated with virulence, are retained within the cell wall, indicating that additional cell wall polymers are involved in their retention. PMID- 27185832 TI - Correction: TspanC8 tetraspanins regulate ADAM10/Kuzbanian trafficking and promote Notch activation in flies and mammals. PMID- 27185831 TI - How Mesp1 makes a move. AB - The transcription factors Mesp1 and Mesp2 have essential roles in the migration and specification of multipotent progenitor cells at the onset of cardiogenesis. Chiapparo et al. (2016. J. Cell Biol http://dx.doi.org/10.1083/jcb.201505082) identify common Mesp functions in fate specification and Mesp1-specific targets controlling the speed and direction of progenitor cell migration. PMID- 27185835 TI - The structured core of human beta tubulin confers isotype-specific polymerization properties. AB - Diversity in cytoskeleton organization and function may be achieved through variations in primary sequence of tubulin isotypes. Recently, isotype functional diversity has been linked to a "tubulin code" in which the C-terminal tail, a region of substantial sequence divergence between isotypes, specifies interactions with microtubule-associated proteins. However, it is not known whether residue changes in this region alter microtubule dynamic instability. Here, we examine recombinant tubulin with human beta isotype IIB and characterize polymerization dynamics. Microtubules with betaIIB have catastrophe frequencies approximately threefold lower than those with isotype betaIII, a suppression similar to that achieved by regulatory proteins. Further, we generate chimeric beta tubulins with native tail sequences swapped between isotypes. These chimeras have catastrophe frequencies similar to that of the corresponding full-length construct with the same core sequence. Together, our data indicate that residue changes within the conserved beta tubulin core are largely responsible for the observed isotype-specific changes in dynamic instability parameters and tune tubulin's polymerization properties across a wide range. PMID- 27185833 TI - Mesp1 controls the speed, polarity, and directionality of cardiovascular progenitor migration. AB - During embryonic development, Mesp1 marks the earliest cardiovascular progenitors (CPs) and promotes their specification, epithelial-mesenchymal transition (EMT), and cardiovascular differentiation. However, Mesp1 deletion in mice does not impair initial CP specification and early cardiac differentiation but induces cardiac malformations thought to arise from a defect of CP migration. Using inducible gain-of-function experiments during embryonic stem cell differentiation, we found that Mesp2, its closest homolog, was as efficient as Mesp1 at promoting CP specification, EMT, and cardiovascular differentiation. However, only Mesp1 stimulated polarity and directional cell migration through a cell-autonomous mechanism. Transcriptional analysis and chromatin immunoprecipitation experiments revealed that Mesp1 and Mesp2 activate common target genes that promote CP specification and differentiation. We identified two direct Mesp1 target genes, Prickle1 and RasGRP3, that are strongly induced by Mesp1 and not by Mesp2 and that control the polarity and the speed of cell migration. Altogether, our results identify the molecular interface controlled by Mesp1 that links CP specification and cell migration. PMID- 27185834 TI - Diaphanous formin mDia2 regulates CENP-A levels at centromeres. AB - Centromeres of higher eukaryotes are epigenetically defined by centromere protein A (CENP-A), a centromere-specific histone H3 variant. The incorporation of new CENP-A into centromeres to maintain the epigenetic marker after genome replication in S phase occurs in G1 phase; however, how new CENP-A is loaded and stabilized remains poorly understood. Here, we identify the formin mDia2 as essential for stable replenishment of new CENP-A at centromeres. Quantitative imaging, pulse-chase analysis, and high-resolution ratiometric live-cell studies demonstrate that mDia2 and its nuclear localization are required to maintain CENP A levels at centromeres. Depletion of mDia2 results in a prolonged centromere association of holiday junction recognition protein (HJURP), the chaperone required for CENP-A loading. A constitutively active form of mDia2 rescues the defect in new CENP-A loading caused by depletion of male germ cell Rac GTPase activating protein (MgcRacGAP), a component of the small GTPase pathway essential for CENP-A maintenance. Thus, the formin mDia2 functions downstream of the MgcRacGAP-dependent pathway in regulating assembly of new CENP-A containing nucleosomes at centromeres. PMID- 27185836 TI - Asterless is required for centriole length control and sperm development. AB - Centrioles are the foundation of two organelles, centrosomes and cilia. Centriole numbers and functions are tightly controlled, and mutations in centriole proteins are linked to a variety of diseases, including microcephaly. Loss of the centriole protein Asterless (Asl), the Drosophila melanogaster orthologue of Cep152, prevents centriole duplication, which has limited the study of its nonduplication functions. Here, we identify populations of cells with Asl-free centrioles in developing Drosophila tissues, allowing us to assess its duplication-independent function. We show a role for Asl in controlling centriole length in germline and somatic tissue, functioning via the centriole protein Cep97. We also find that Asl is not essential for pericentriolar material recruitment or centrosome function in organizing mitotic spindles. Lastly, we show that Asl is required for proper basal body function and spermatid axoneme formation. Insights into the role of Asl/Cep152 beyond centriole duplication could help shed light on how Cep152 mutations lead to the development of microcephaly. PMID- 27185837 TI - DSCR1 is required for both axonal growth cone extension and steering. AB - Local information processing in the growth cone is essential for correct wiring of the nervous system. As an axon navigates through the developing nervous system, the growth cone responds to extrinsic guidance cues by coordinating axon outgrowth with growth cone steering. It has become increasingly clear that axon extension requires proper actin polymerization dynamics, whereas growth cone steering involves local protein synthesis. However, molecular components integrating these two processes have not been identified. Here, we show that Down syndrome critical region 1 protein (DSCR1) controls axon outgrowth by modulating growth cone actin dynamics through regulation of cofilin activity (phospho/dephospho-cofilin). Additionally, DSCR1 mediates brain-derived neurotrophic factor-induced local protein synthesis and growth cone turning. Our study identifies DSCR1 as a key protein that couples axon growth and pathfinding by dually regulating actin dynamics and local protein synthesis. PMID- 27185839 TI - When the Minimal Becomes Measurable. PMID- 27185840 TI - Reply to C.S. Hourigan et al. PMID- 27185838 TI - Validation of a Prediction Tool for Chemotherapy Toxicity in Older Adults With Cancer. AB - PURPOSE: Older adults are at increased risk for chemotherapy toxicity, and standard oncology assessment measures cannot identify those at risk. A predictive model for chemotherapy toxicity was developed (N = 500) that consisted of geriatric assessment questions and other clinical variables. This study aims to externally validate this model in an independent cohort (N = 250). PATIENTS AND METHODS: Patients age >= 65 years with a solid tumor, fluent in English, and who were scheduled to receive a new chemotherapy regimen were recruited from eight institutions. Risk of chemotherapy toxicity was calculated (low, medium, or high risk) on the basis of the prediction model before the start of chemotherapy. Chemotherapy-related toxicity was captured (grade 3 [hospitalization indicated], grade 4 [life threatening], and grade 5 [treatment-related death]). Validation of the prediction model was performed by calculating the area under the receiver operating characteristic curve. RESULTS: The study sample (N = 250) had a mean age of 73 years (range, 65 to 94 [standard deviation, 5.8]). More than one half of patients (58%) experienced grade >= 3 toxicity. Risk of toxicity increased with increasing risk score (36.7% low, 62.4% medium, 70.2% high risk; P < .001). The area under the curve of the receiver-operating characteristic curve was 0.65 (95% CI, 0.58 to 0.71), which was not statistically different from the development cohort (0.72; 95% CI, 0.68 to 0.77; P = .09). There was no association between Karnofsky Performance Status and chemotherapy toxicity (P = .25). CONCLUSION: This study externally validated a chemotherapy toxicity predictive model for older adults with cancer. This predictive model should be considered when discussing the risks and benefits of chemotherapy with older adults. PMID- 27185841 TI - Obvious Pitfall in the Estimation of Renal Dysfunction. PMID- 27185842 TI - Paclitaxel, Ifosfamide, and Cisplatin Efficacy for First-Line Treatment of Patients With Intermediate- or Poor-Risk Germ Cell Tumors. AB - PURPOSE: Paclitaxel, ifosfamide, and cisplatin (TIP) achieved complete responses (CRs) in two thirds of patients with advanced germ cell tumors (GCTs) who relapsed after first-line chemotherapy with cisplatin and etoposide with or without bleomycin. We tested the efficacy of first-line TIP in patients with intermediate- or poor-risk disease. PATIENTS AND METHODS: In this prospective, multicenter, single-arm phase II trial, previously untreated patients with International Germ Cell Cancer Collaborative Group poor-risk or modified intermediate-risk GCTs received four cycles of TIP (paclitaxel 240 mg/m(2) over 2 days, ifosfamide 6 g/m(2) over 5 days with mesna support, and cisplatin 100 mg/m(2) over 5 days) once every 3 weeks with granulocyte colony-stimulating factor support. The primary end point was the CR rate. RESULTS: Of the first 41 evaluable patients, 28 (68%) achieved a CR, meeting the primary efficacy end point. After additional accrual on an extension phase, total enrollment was 60 patients, including 40 (67%) with poor risk and 20 (33%) with intermediate risk. Thirty-eight (68%) of 56 evaluable patients achieved a CR and seven (13%) achieved partial responses with negative markers (PR-negative) for a favorable response rate of 80%. Five of seven achieving PR-negative status had seminoma and therefore did not undergo postchemotherapy resection of residual masses. Estimated 3-year progression-free survival and overall survival rates were 72% (poor risk, 63%; intermediate risk, 90%) and 91% (poor risk, 87%; intermediate risk, 100%), respectively. Grade 3 to 4 toxicities consisted primarily of reversible hematologic or electrolyte abnormalities, including neutropenic fever in 18%. CONCLUSION: TIP demonstrated efficacy as first-line therapy for intermediate- and poor-risk GCTs with an acceptable safety profile. Given higher rates of favorable response, progression-free survival, and overall survival compared with prior first-line studies, TIP warrants further study in this population. PMID- 27185844 TI - Reply to C.S. Hourigan et al. PMID- 27185846 TI - Top 50 Most-Cited Journal of Clinical Oncology Articles From 2013. PMID- 27185843 TI - Randomized Phase II Study of Trabectedin and Doxorubicin Compared With Doxorubicin Alone as First-Line Treatment in Patients With Advanced Soft Tissue Sarcomas: A Spanish Group for Research on Sarcoma Study. AB - PURPOSE: Doxorubicin and trabectedin are considered active drugs in soft tissue sarcoma (STS). The combination of both drugs was hypothesized to be advantageous and safe on the basis of preclinical evidence and a previous phase I trial, respectively. The aim of this study was to compare the clinical outcome of trabectedin plus doxorubicin with doxorubicin as first-line treatment of advanced STS patients. PATIENTS AND METHODS: In this open-label randomized phase II trial, the main end point was progression-free survival (PFS). Trabectedin 1.1 mg/m(2) in a 3-hour infusion plus doxorubicin 60 mg/m(2) as the experimental arm and doxorubicin 75 mg/m(2) as the control arm were administered for up to six cycles. Translational research was planned to correlate the expression of apoptotic and DNA repair genes with clinical outcome. RESULTS: In 115 randomly assigned patients, the median PFS was 5.5 months in the control arm and 5.7 months in the experimental arm (hazard ratio, 1.16; 95% CI, 0.79 to 1.71; P = .45) in the intent-to-treat analysis. The trial was stopped for futility after the interim analysis, because the results in the experimental arm showed the risk reduction for the main end point to be < 9.64%. The proportion of patients with grade 3 or 4 thrombocytopenia, asthenia, and liver toxicity was significantly higher in the experimental arm. FAS and p53 were shown to be prognostic factors for PFS (7.0 months if FAS+ and p53-; 3.4 months if FAS+/p53+ or FAS-/p53-; and 0.7 months if FAS- and p53+; P < .001) and for overall survival. CONCLUSION: Trabectedin plus doxorubicin did not show superiority over doxorubicin alone as first-line treatment of advanced STS. The prognostic role of apoptotic key genes, FAS and p53, was shown to be robust enough to continue this research line. PMID- 27185847 TI - Renal Dysfunction Has Statistically and Clinically Significant Deleterious Effects on Anticancer Drug Safety. PMID- 27185845 TI - Reply to V. Launay-Vacher, T. Shimokata et al, and C. Porta et al. PMID- 27185848 TI - Reply to H. Laubli et al. PMID- 27185850 TI - Still Refining Adjuvant Endocrine Therapy in Premenopausal Women: Not Too Much, Not Too Little. PMID- 27185849 TI - Minimal Treatment of Low-Risk, Pediatric Lymphocyte-Predominant Hodgkin Lymphoma: A Report From the Children's Oncology Group. AB - PURPOSE: Children's Oncology Group study AHOD03P1 was designed to determine whether excellent outcomes can be maintained for patients with low-risk, pediatric lymphocyte-predominant Hodgkin lymphoma (LPHL) with a strategy of resection alone or minimal chemotherapy. PATIENTS AND METHODS: Patients with stage IA LPHL in a single node that was completely resected were observed without further therapy; recurrences were treated with three cycles of doxorubicin/vincristine/prednisone/cyclophosphamide (AV-PC). Patients with unresected stage IA or stage IIA LPHL were treated with three cycles of AV-PC. Patients with less than a complete response (CR) to AV-PC received 21-Gy involved field radiation therapy (IFRT). RESULTS: A total of 183 eligible patients were enrolled; 178 were evaluable. Of these, 52 patients underwent complete resection of a single node. There were 13 relapses at a median of 11.5 months; 5-year event free survival (EFS) was 77% (range, 62% to 87%). A total of 135 patients received AV-PC; 126 were treated at diagnosis and nine at relapse after surgery alone. Eleven patients receiving AV-PC had less than CR and received IFRT. Fourteen first events occurred among 135 patients (12 relapses and two second malignancies). Two relapses occurred in patients who had received IFRT. Five-year EFS was 88.8% (95% CI, 81.8% to 93.2%). Five-year EFS for the entire cohort was 85.5% (95% CI, 79.2% to 90.1%); overall survival was 100%. CONCLUSION: Some 75% of highly selected pediatric patients with LPHL may be spared chemotherapy after surgical resection alone. Pediatric LPHL has excellent EFS with chemotherapy that is less intensive than standard regimens; > 90% of patients can avoid radiation therapy. The salvage rate for the few relapses is high, with 100% survival overall. PMID- 27185851 TI - Antimetastatic Properties of Low Molecular Weight Heparin. PMID- 27185852 TI - Harmonization of Renal Function Assessment Is Needed Throughout the Whole Process of Anticancer Drug Development. PMID- 27185853 TI - A neuroprotective role for microglia in prion diseases. AB - Microglial activation is a hallmark of most neurodegenerative disorders, and is particularly conspicuous in prion diseases. However, the role of microglia, which function as both primary immune effector cells and professional phagocytes in the central nervous system, remains contentious in the context of neurodegeneration. Here, we evaluated the effect of microglial depletion/deficiency on prion pathogenesis. We found that ganciclovir-mediated microglial ablation on tga20/CD11b-thymidine kinase of Herpes simplex virus (HSVTK) cerebellar organotypic cultured slices markedly aggravated prion-induced neurotoxicity. A similar deterioration of disease was recapitulated in in vivo microglial depletion in prion-infected tga20/CD11b-HSVTK mice. Additionally, deficiency of microglia in interleukin 34 knockout (IL34(-/-)) mice again resulted in significantly augmented proteinase K-resistant prion protein deposition and accelerated prion disease progression. These results provide unambiguous evidence for a general protective role of microglia in prion pathogenesis. PMID- 27185854 TI - The transcription factor Zeb2 regulates development of conventional and plasmacytoid DCs by repressing Id2. AB - Plasmacytoid dendritic cells (DCs [pDCs]) develop from pre-pDCs, whereas two lineages of conventional DCs (cDCs; cDC1s and cDC2s) develop from lineage committed pre-cDCs. Several transcription factors (TFs) have been implicated in regulating the development of pDCs (E2-2 and Id2) and cDC1s (Irf8, Id2, and Batf3); however, those required for the early commitment of pre-cDCs toward the cDC2 lineage are unknown. Here, we identify the TF zinc finger E box-binding homeobox 2 (Zeb2) to play a crucial role in regulating DC development. Zeb2 was expressed from the pre-pDC and pre-cDC stage onward and highly expressed in mature pDCs and cDC2s. Mice conditionally lacking Zeb2 in CD11c(+) cells had a cell-intrinsic reduction in pDCs and cDC2s, coupled with an increase in cDC1s. Conversely, mice in which CD11c(+) cells overexpressed Zeb2 displayed a reduction in cDC1s. This was accompanied by altered expression of Id2, which was up regulated in cDC2s and pDCs from conditional knockout mice. Zeb2 chromatin immunoprecipitation analysis revealed Id2 to be a direct target of Zeb2. Thus, we conclude that Zeb2 regulates commitment to both the cDC2 and pDC lineages through repression of Id2. PMID- 27185855 TI - A nonsense mutation in the DNA repair factor Hebo causes mild bone marrow failure and microcephaly. AB - Inherited bone marrow failure syndromes are human conditions in which one or several cell lineages of the hemopoietic system are affected. They are present at birth or may develop progressively. They are sometimes accompanied by other developmental anomalies. Three main molecular causes have been recognized to result in bone marrow failure syndromes: (1) defects in the Fanconi anemia (FA)/BRCA DNA repair pathway, (2) defects in telomere maintenance, and (3) abnormal ribosome biogenesis. We analyzed a patient with mild bone marrow failure and microcephaly who did not present with the typical FA phenotype. Cells from this patient showed increased sensitivity to ionizing radiations and phleomycin, attesting to a probable DNA double strand break (dsb) repair defect. Linkage analysis and whole exome sequencing revealed a homozygous nonsense mutation in the ERCC6L2 gene. We identified a new ERCC6L2 alternative transcript encoding the DNA repair factor Hebo, which is critical for complementation of the patient's DNAdsb repair defect. Sequence analysis revealed three structured regions within Hebo: a TUDOR domain, an adenosine triphosphatase domain, and a new domain, HEBO, specifically present in Hebo direct orthologues. Hebo is ubiquitously expressed, localized in the nucleus, and rapidly recruited to DNAdsb's in an NBS1-dependent manner. PMID- 27185856 TI - Bridging channel dendritic cells induce immunity to transfused red blood cells. AB - Red blood cell (RBC) transfusion is a life-saving therapeutic tool. However, a major complication in transfusion recipients is the generation of antibodies against non-ABO alloantigens on donor RBCs, potentially resulting in hemolysis and renal failure. Long-lived antibody responses typically require CD4(+) T cell help and, in murine transfusion models, alloimmunization requires a spleen. Yet, it is not known how RBC-derived antigens are presented to naive T cells in the spleen. We sought to answer whether splenic dendritic cells (DCs) were essential for T cell priming to RBC alloantigens. Transient deletion of conventional DCs at the time of transfusion or splenic DC preactivation before RBC transfusion abrogated T and B cell responses to allogeneic RBCs, even though transfused RBCs persisted in the circulation for weeks. Although all splenic DCs phagocytosed RBCs and activated RBC-specific CD4(+) T cells in vitro, only bridging channel 33D1(+) DCs were required for alloimmunization in vivo. In contrast, deletion of XCR1(+)CD8(+) DCs did not alter the immune response to RBCs. Our work suggests that blocking the function of one DC subset during a narrow window of time during RBC transfusion could potentially prevent the detrimental immune response that occurs in patients who require lifelong RBC transfusion support. PMID- 27185857 TI - Two distinct voltage-sensing domains control voltage sensitivity and kinetics of current activation in CaV1.1 calcium channels. AB - Alternative splicing of the skeletal muscle CaV1.1 voltage-gated calcium channel gives rise to two channel variants with very different gating properties. The currents of both channels activate slowly; however, insertion of exon 29 in the adult splice variant CaV1.1a causes an ~30-mV right shift in the voltage dependence of activation. Existing evidence suggests that the S3-S4 linker in repeat IV (containing exon 29) regulates voltage sensitivity in this voltage sensing domain (VSD) by modulating interactions between the adjacent transmembrane segments IVS3 and IVS4. However, activation kinetics are thought to be determined by corresponding structures in repeat I. Here, we use patch-clamp analysis of dysgenic (CaV1.1 null) myotubes reconstituted with CaV1.1 mutants and chimeras to identify the specific roles of these regions in regulating channel gating properties. Using site-directed mutagenesis, we demonstrate that the structure and/or hydrophobicity of the IVS3-S4 linker is critical for regulating voltage sensitivity in the IV VSD, but by itself cannot modulate voltage sensitivity in the I VSD. Swapping sequence domains between the I and the IV VSDs reveals that IVS4 plus the IVS3-S4 linker is sufficient to confer CaV1.1a-like voltage dependence to the I VSD and that the IS3-S4 linker plus IS4 is sufficient to transfer CaV1.1e-like voltage dependence to the IV VSD. Any mismatch of transmembrane helices S3 and S4 from the I and IV VSDs causes a right shift of voltage sensitivity, indicating that regulation of voltage sensitivity by the IVS3-S4 linker requires specific interaction of IVS4 with its corresponding IVS3 segment. In contrast, slow current kinetics are perturbed by any heterologous sequences inserted into the I VSD and cannot be transferred by moving VSD I sequences to VSD IV. Thus, CaV1.1 calcium channels are organized in a modular manner, and control of voltage sensitivity and activation kinetics is accomplished by specific molecular mechanisms within the IV and I VSDs, respectively. PMID- 27185858 TI - TRPM7 is a molecular substrate of ATP-evoked P2X7-like currents in tumor cells. AB - Within the ion channel-coupled purine receptor (P2X) family, P2X7 has gained particular interest because of its role in immune responses and in the growth control of several malignancies. Typical hallmarks of P2X7 are nonselective and noninactivating cation currents that are elicited by high concentrations (0.1-10 mM) of extracellular ATP. Here, we observe spurious ATP-induced currents in HEK293 cells that neither express P2X7 nor display ATP-induced Ca(2+) influx or Yo-Pro-1 uptake. Although the biophysical properties of these ionic currents resemble those of P2X7 in terms of their reversal potential close to 0 mV, nonrectifying current-voltage relationship, current run-up during repeated ATP application, and augmentation in bath solutions containing low divalent cation (DIC) concentrations, they are poorly inhibited by established P2X7 antagonists. Because high ATP concentrations reduce the availability of DICs, these findings prompted us to ask whether other channel entities may become activated by our experimental regimen. Indeed, a bath solution with no added DICs yields similar currents and also a rapidly inactivating Na(+)-selective conductance. We provide evidence that TRPM7 and ASIC1a (acid-sensing ion channel type Ia)-like channels account for these noninactivating and phasic current components, respectively. Furthermore, we find ATP-induced currents in rat C6 glioma cells, which lack functional P2X receptors but express TRPM7. Thus, the observation of an atypical P2X7-like conductance may be caused by the activation of TRPM7 by ATP, which scavenges free DICs and thereby releases TRPM7 from permeation block. Because TRPM7 has a critical role in controlling the intracellular Mg(2+) homeostasis and regulating tumor growth, these data imply that the proposed role of P2X7 in C6 glioma cell proliferation deserves reevaluation. PMID- 27185861 TI - 'Two Minds with but a Single Thought ...'. PMID- 27185859 TI - Endothelial HO-1 induction by model TG-rich lipoproteins is regulated through a NOX4-Nrf2 pathway. AB - Circulating levels of chylomicron remnants (CMRs) increase postprandially and their composition directly reflects dietary lipid intake. These TG-rich lipoproteins likely contribute to the development of endothelial dysfunction, albeit via unknown mechanisms. Here, we investigated how the FA composition of CMRs influences their actions on human aortic endothelial cells (HAECs) by comparing the effects of model CMRs-artificial TG-rich CMR-like particles (A CRLPs)-containing TGs extracted from fish, DHA-rich algal, corn, or palm oils. HAECs responded with distinct transcriptional programs according to A-CRLP TG content and oxidation status, with genes involved in antioxidant defense and cytoprotection most prominently affected by n-3 PUFA-containing A-CRLPs. These particles were significantly more efficacious inducers of heme oxygenase-1 (HO-1) than n-6 PUFA corn or saturated FA-rich palm CRLPs. Mechanistically, HO-1 induction by all CRLPs requires NADPH oxidase 4, with PUFA-containing particles additionally dependent upon mitochondrial reactive oxygen species. Activation of both p38 MAPK and PPARbeta/delta culminates in increased nuclear factor erythroid 2-related factor 2 (Nrf2) expression/nuclear translocation and HO-1 induction. These studies define new molecular pathways coupling endothelial cell activation by model CMRs with adaptive regulation of Nrf2-dependent HO-1 expression and may represent key mechanisms through which dietary FAs differentially impact progression of endothelial dysfunction. PMID- 27185862 TI - T cell adhesion triggers an early signaling pole distal to the immune synapse. AB - The immunological synapse forms at the interface between a T cell and an antigen presenting cell after foreign antigen recognition. The immunological synapse is considered to be the site where the signaling cascade leading to T lymphocyte activation is triggered. Here, we show that another signaling region can be detected before formation of the synapse at the opposite pole of the T cell. This structure appears during the first minute after the contact forms, is transient and contains all the classic components that have been previously described at the immunological synapse. Its formation is independent of antigen recognition but is driven by adhesion itself. It constitutes a reservoir of signaling molecules that are potentially ready to be sent to the immunological synapse through a microtubule-dependent pathway. The antisynapse can thus be considered as a pre-synapse that is triggered independently of antigen recognition. PMID- 27185860 TI - Partitioning-Defective 1a/b Depletion Impairs Glomerular and Proximal Tubule Development. AB - The kidney is a highly polarized epithelial organ that develops from undifferentiated mesenchyme, although the mechanisms that regulate the development of renal epithelial polarity are incompletely understood. Partitioning-defective 1 (Par1) proteins have been implicated in cell polarity and epithelial morphogenesis; however, the role of these proteins in the developing kidney has not been established. Therefore, we studied the contribution of Par1a/b to renal epithelial development. We examined the renal phenotype of newborn compound mutant mice carrying only one allele of Par1a or Par1b. Loss of three out of four Par1a/b alleles resulted in severe renal hypoplasia, associated with impaired ureteric bud branching. Compared with kidneys of newborn control littermates, kidneys of newborn mutant mice exhibited dilated proximal tubules and immature glomeruli, and the renal proximal tubular epithelia lacked proper localization of adhesion complexes. Furthermore, Par1a/b mutants expressed low levels of renal Notch ligand Jag1, activated Notch2, and Notch effecter Hes1. Together, these data demonstrate that Par1a/b has a key role in glomerular and proximal tubule development, likely via modulation of Notch signaling. PMID- 27185863 TI - Retinoic-acid-mediated HRas stabilization induces neuronal differentiation of neural stem cells during brain development. AB - Ras signaling is tightly regulated during neural stem cell (NSC) differentiation, and defects in this pathway result in aberrant brain development. However, the mechanism regulating Ras signaling during NSC differentiation was unknown. Here, we show that stabilized HRas specifically induces neuronal differentiation of NSCs. Lentivirus-mediated HRas overexpression and knockdown resulted in stimulation and inhibition, respectively, of NSC differentiation into neuron in the ex vivo embryo. Retinoic acid, an active metabolite of vitamin A, promoted neuronal differentiation of NSCs by stabilizing HRas, and HRas knockdown blocked the retinoic acid effect. Vitamin-A-deficient mice displayed abnormal brain development with reduced HRas levels and a reduced thickness of the postmitotic region containing differentiated neurons. All of these abnormal phenotypes were rescued with the restoration of HRas protein levels achieved upon feeding with a retinoic-acid-supplemented diet. In summary, this study shows that retinoic acid stabilizes HRas protein during neurogenesis, and that this is required for NSC differentiation into neurons and murine brain development. PMID- 27185864 TI - Cdk-dependent phosphorylation regulates TRF1 recruitment to PML bodies and promotes C-circle production in ALT cells. AB - TRF1, a duplex telomeric DNA binding protein, is implicated in homologous recombination-based alternative lengthening of telomeres, known as ALT. However, how TRF1 promotes ALT activity has yet to be fully characterized. Here we report that Cdk-dependent TRF1 phosphorylation on T371 acts as a switch to create a pool of TRF1, referred to as (pT371)TRF1, which is recruited to ALT-associated PML bodies (APBs) in S and G2 phases independently of its binding to telomeric DNA. We find that phosphorylation of T371 is essential for APB formation and C-circle production, both of which are hallmarks of ALT. We show that the interaction of (pT371)TRF1 with APBs is dependent upon ATM and homologous-recombination promoting factors Mre11 and BRCA1. In addition, (pT371)TRF1 interaction with APBs is sensitive to transcription inhibition, which also reduces DNA damage at telomeres. Furthermore, overexpression of RNaseH1 impairs (pT371)TRF1 recruitment to APBs in the presence of campothecin, an inhibitor that prevents topoisomerase I from resolving RNA-DNA hybrids. These results suggest that transcription associated DNA damage, perhaps arising from processing RNA-DNA hybrids at telomeres, triggers (pT371)TRF1 recruitment to APBs to facilitate ALT activity. PMID- 27185865 TI - CEP295 interacts with microtubules and is required for centriole elongation. AB - Centriole duplication is a tightly ordered process during which procentrioles are assembled in G1-S and elongate during S and G2. Here, we show that human CEP295 (Drosophila Ana1) is not essential for initial cartwheel assembly, but is required to build distal half centrioles during S and G2. Using super-resolution and immunogold electron microscopy, we demonstrate that CEP295 is recruited to the proximal end of procentrioles in early S phase, when it is also localized at the centriolar microtubule wall that surrounds the human SAS6 cartwheel hub. Interestingly, depletion of CEP295 not only inhibits the recruitments of POC5 and POC1B to the distal half centrioles in G2, resulting in shorter centrioles, it also blocks the post-translational modification of centriolar microtubules (e.g. acetylation and glutamylation). Importantly, our results indicate that CEP295 directly interacts with microtubules, and that excess CEP295 could induce the assembly of overly long centrioles. Furthermore, exogenous expression of the N terminal domain of CEP295 exerts a dominant-negative effect on centriole elongation. Collectively, these findings suggest that CEP295 is essential for building the distal half centrioles and for post-translational modification of centriolar microtubules. PMID- 27185866 TI - Long-term glucocorticoid effect on bone mineral density in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. AB - INTRODUCTION: Patients with 21-hydroxylase deficiency (21OHD) assume a lifelong glucocorticoid (GC) therapy. Excessive GC treatment increases the risk of osteoporosis and bone fractures, even though the role of substitutive therapy is not fully established: we analyzed the effect of GC dose on bone metabolism and bone mineral density (BMD) over time in patients with 21OHD. METHODS: We studied bone metabolism markers and BMD in 38 adult patients with 21OHD (19-47 years, 24 females and 14 males) and 38 matched healthy control. In 15 patients, BMD data were available at both baseline and after a long-term follow-up. RESULTS: BMD was lower in patients than in controls at lumbar spine (0.961+/-0.1g/cm(2) vs 1.02+/ 0.113g/cm(2), P=0.014) and femur neck (0.736+/-0.128g/cm(2) vs 0.828+/ 0.103g/cm(2), P=0.02); otherwise, after height correction, only femoral neck BMD was lower in patients (0.458+/-0.081g/cm(2) vs 0.498+/-0.063g/cm(2), P=0.028). In those 21OHD subjects with at least 10 years follow-up, we observed an increase in lumbar BMD (P=0.0429) and a decrease in femur neck BMD values (P=0.004). Cumulative GC dose was not related to bone metabolism or BMD. No patient experienced clinical fragility fractures. CONCLUSIONS: BMD values are decreased in patients with 21OHD, which are in part explained by decreased height, but not by the dose of glucocorticoids. Nevertheless, bone status should be carefully monitored in patients with 21OHD. PMID- 27185868 TI - Polymorphisms in MEN1 and DRD2 genes are associated with the occurrence and characteristics of pituitary adenomas. AB - OBJECTIVE: Although pituitary adenomas (PAs) affect a significant proportion of the population, only a fraction have the potential to become clinically relevant during an individual's lifetime, causing hormonal imbalance or complications due to mass effect. The overwhelming majority of cases are sporadic and without a clear familial history, and the genotype-phenotype correlation in PA patients is poorly understood. Our aim was to investigate the involvement of genes known for their role in familial cases on drug response and tumor suppression in the development and pathology of PAs in a patient group from Latvia. DESIGN: The study included 143 cases and 354 controls, we investigated the role of single nucleotide polymorphisms (SNPs) in seven genes (SSTR2, SSTR5, DRD2, MEN1, AIP, GNAS, and PRKAR1A) associated with pituitary tumor occurrence, phenotype, and clinical symptoms. METHODS: Genotyping of 96 tag and nonsynonymous SNPs was performed in the genomic regions of interest. RESULTS: We discovered a significant association (OR=17.8, CI 0.95=2.18-145.5, P=0.0002) between a rare MEN1 mutation (rs2959656) and clinically active adenoma in our patients. Additionally, rs7131056 at DRD2 was associated with a higher occurrence of extrasellar growth in patients with prolactinoma and somatotropinoma (OR=2.79, CI 0.95=1.58-4.95, P=0.0004). CONCLUSIONS: rs2959656, a nonsynonymous variant in MEN1, is associated with the development of clinically active PA. Furthermore, rs7131056 in DRD2 contributes to either faster growth of the adenoma or reduced symptomatic presentation, allowing PAs to become larger before detection. PMID- 27185867 TI - Molecular CYP21A2 diagnosis in 480 Brazilian patients with congenital adrenal hyperplasia before newborn screening introduction. AB - BACKGROUND: Most congenital adrenal hyperplasia (CAH) patients carry CYP21A2 mutations derived from conversion events involving the pseudogene, and the remaining carry new mutations. OBJECTIVE: To review causal mutations and genotype phenotype correlation in 480 Brazilian patients. METHODS: DNA was extracted from 158 salt-wasters (SWs), 116 simple virilizing (SV), and 206 nonclassical (NC) patients. Fourteen point mutations were screened by allele-specific PCR, large rearrangements by Southern blotting/MLPA, and sequencing was performed in those with incomplete genotype. The gene founder effect was analyzed by microsatellite studies. Patients were divided into six genotypes (Null; A: <2%; B: 3-7%; C: >20% of residual enzymatic activity (EA); D: unknown EA; E: incomplete genotype). RESULTS: Targeted methodologies defined genotype in 87.6% of classical and in 80% of NC patients and the addition of sequencing in 100 and 83.5%, respectively. The most frequent mutations were p.V281L (26.6% of alleles), IVS2-13A/C>G (21.1%), and p.I172N (7.5%); seven rare mutations and one novel mutation (p.E351V) were identified. Gene founder effect was observed in all but one (p.W19X) mutation. Null, A, B, and C genotypes correlated with SW (88%), SW (70%), SV (98%), and NC forms (100%), respectively. In group D, the p.E351V mutation correlated with classical form and group E comprised exclusively NC-patients. ACTH-stimulated 17OHP level of 44.3ng/mL was the best cutoff to identify NC-patients carrying severe mutations. CONCLUSIONS: We identified a good genotype-phenotype correlation in CAH, providing useful data regarding prediction of disease's severity; moreover, we suggest that ACTH-stimulated 17OHP levels could predict carrier status for severe mutations. Sequencing is essential to optimize molecular diagnosis in Brazilian CAH patients. PMID- 27185869 TI - Insulin resistance as a predictor of venous thromboembolism in breast cancer. PMID- 27185870 TI - New drugs for medullary thyroid cancer: new promises? AB - Medullary thyroid cancer (MTC) is a rare tumor arising from the calcitonin producing parafollicular C cells of the thyroid gland, occurring either sporadically or alternatively in a hereditary form based on germline RET mutations in approximately one-third of cases. Historically, patients with advanced, metastasized MTC have had a poor prognosis, partly due to limited response to conventional chemotherapy and radiation therapy. In the past decade, however, considerable progress has been made in identifying key genetic alterations and dysregulated signaling pathways paving the way for the evaluation of a series of multitargeted kinase inhibitors that have started to meaningfully impact clinical practice. Two drugs, vandetanib and cabozantinib, are now approved in the US and EU for use in advanced, progressive MTC, with additional targeted agents also showing promise or awaiting results from clinical trials. However, the potential for toxicities with significant reduction in quality of life and lack of curative outcomes has to be carefully weighed against potential for benefit. Despite significant PFS prolongation observed in randomized clinical trials, most patients even with metastatic disease enjoy indolent courses with slow progression observed over years, wherein watchful waiting is still the preferred strategy. As advanced, progressive MTC is a rare and complex disease, a multidisciplinary approach centered in specialized centers providing interdisciplinary expertise in the individualization of available therapeutic options is preferred. In this review, we summarize current concepts of the molecular pathogenesis of advanced MTC and discuss results from clinical trials of targeted agents and also cytotoxic chemotherapy in the context of clinical implications and future perspectives. PMID- 27185871 TI - Mortality in acromegaly: a 20-year follow-up study. AB - OBJECTIVE: It is unclear whether mortality still is increased in acromegaly and whether there are gender-related differences. We dynamically assessed outcome during long-term follow-up in our nationwide cohort. PATIENTS AND METHODS: We studied standardized mortality ratios (SMRs) relative to the general population and causes of death in acromegaly (n=333) compared with age- and gender-matched controls (n=4995). RESULTS: During 20 (0-33) years follow-up, 113 (34%) patients (n=333, 52% women) and 1334 (27%) controls (n=4995) died (P=0.004). SMR (1.9, 95% CI: 1.53-2.34, P<0.001) and all-cause mortality (OR 1.6, 95% CI: 1.2-2.2, P<0.001) were increased in acromegaly. Overall distribution of causes of death (P<0.001) differed between patients and controls but not cardiovascular (34% vs 33%) or cancer deaths (27% vs 27%). In acromegaly, but not in controls, causes of deaths shifted from 44% cardiovascular and 28% cancer deaths during the first decade, to 23% cardiovascular and 35% cancer deaths during the next two decades. In acromegaly, cancer deaths were mostly attributed to pancreatic adenocarcinoma (n=5), breast (n=4), lung (n=3) and colon (n=3) carcinoma. In acromegaly, men were younger than women at diagnosis (median 44.5 vs 50 years, P<0.001) and death (67 vs 76 years, P=0.0015). Compared with controls, women (36% vs 25%, P<0.01), but not men (31% vs 28%, P=0.44), had increased mortality. CONCLUSIONS: In acromegaly, men are younger at diagnosis and death than women. Compared with controls, mortality is increased during 20 years of follow-up, especially in women. Causes of deaths shift from predominantly cardiovascular to cancer deaths. PMID- 27185872 TI - IGF2 and IGF1R in pediatric adrenocortical tumors: roles in metastasis and steroidogenesis. AB - Deregulation of the IGF system observed in human tumors indicates a role in malignant cell transformation and in tumor cell proliferation. Although overexpression of the IGF2 and IGF1R genes was described in adrenocortical tumors (ACTs), few studies reported their profiles in pediatric ACTs. In this study, the IGF2 and IGF1R expression was evaluated by RT-qPCR according to the patient's clinical/pathological features in 60 pediatric ACT samples, and IGF1R protein was investigated in 45 samples by immunohistochemistry (IHC). Whole transcriptome and functional assays were conducted after IGF1R inhibition with OSI-906 in NCI-H295A cell line. Significant IGF2 overexpression was found in tumor samples when compared with non-neoplastic samples (P<0.001), significantly higher levels of IGF1R in patients with relapse/metastasis (P=0.031) and moderate/strong IGF1R immunostaining in 62.2% of ACTs, but no other relationship with patient survival and clinical/pathological features was observed. OSI-906 treatment downregulated genes associated with MAPK activity, induced limited reduction of cell viability and increased the apoptosis rate. After 24h, the treatment also decreased the expression of genes related to the steroid biosynthetic process, the protein levels of the steroidogenic acute regulatory protein (STAR), and androgen secretion in cell medium, supporting the role of IGF1R in steroidogenesis of adrenocortical carcinoma cells. Our data showed that the IGF1R overexpression could be indicative of aggressive ACTs in children. However, in vitro treatments with high concentrations of OSI-906 (>1MUM) showed limited reduction of cell viability, suggesting that OSI-906 alone could not be a suitable therapy to abolish carcinoma cell growth. PMID- 27185873 TI - AMPK Phosphorylates Desnutrin/ATGL and Hormone-Sensitive Lipase To Regulate Lipolysis and Fatty Acid Oxidation within Adipose Tissue. AB - The role of AMP-activated protein kinase (AMPK) in promoting fatty acid (FA) oxidation in various tissues, such as liver and muscle, has been well understood. However, the role of AMPK in lipolysis and FA metabolism in adipose tissue has been controversial. To investigate the role of AMPK in the regulation of adipose lipolysis in vivo, we generated mice with adipose-tissue-specific knockout of both the alpha1 and alpha2 catalytic subunits of AMPK (AMPK-ASKO mice) by using aP2-Cre and adiponectin-Cre. Both models of AMPK-ASKO ablation show no changes in desnutrin/ATGL levels but have defective phosphorylation of desnutrin/ATGL at S406 to decrease its triacylglycerol (TAG) hydrolase activity, lowering basal lipolysis in adipose tissue. These mice also show defective phosphorylation of hormone-sensitive lipase (HSL) at S565, with higher phosphorylation at protein kinase A sites S563 and S660, increasing its hydrolase activity and isoproterenol stimulated lipolysis. With higher overall adipose lipolysis, both models of AMPK ASKO mice are lean, having smaller adipocytes with lower TAG and higher intracellular free-FA levels. Moreover, FAs from higher lipolysis activate peroxisome proliferator-activated receptor delta to induce FA oxidative genes and increase FA oxidation and energy expenditure. Overall, for the first time, we provide in vivo evidence of the role of AMPK in the phosphorylation and regulation of desnutrin/ATGL and HSL and thus adipose lipolysis. PMID- 27185874 TI - Evidence for Multiple Mediator Complexes in Yeast Independently Recruited by Activated Heat Shock Factor. AB - Mediator is an evolutionarily conserved coactivator complex essential for RNA polymerase II transcription. Although it has been generally assumed that in Saccharomyces cerevisiae, Mediator is a stable trimodular complex, its structural state in vivo remains unclear. Using the "anchor away" (AA) technique to conditionally deplete select subunits within Mediator and its reversibly associated Cdk8 kinase module (CKM), we provide evidence that Mediator's tail module is highly dynamic and that a subcomplex consisting of Med2, Med3, and Med15 can be independently recruited to the regulatory regions of heat shock factor 1 (Hsf1)-activated genes. Fluorescence microscopy of a scaffold subunit (Med14)-anchored strain confirmed parallel cytoplasmic sequestration of core subunits located outside the tail triad. In addition, and contrary to current models, we provide evidence that Hsf1 can recruit the CKM independently of core Mediator and that core Mediator has a role in regulating postinitiation events. Collectively, our results suggest that yeast Mediator is not monolithic but potentially has a dynamic complexity heretofore unappreciated. Multiple species, including CKM-Mediator, the 21-subunit core complex, the Med2-Med3-Med15 tail triad, and the four-subunit CKM, can be independently recruited by activated Hsf1 to its target genes in AA strains. PMID- 27185875 TI - Brg1 Enables Rapid Growth of the Early Embryo by Suppressing Genes That Regulate Apoptosis and Cell Growth Arrest. AB - SWI/SNF (switching/sucrose nonfermenting)-dependent chromatin remodeling establishes coordinated gene expression programs during development, yet important functional details remain to be elucidated. We show that the Brg1 (Brahma-related gene 1; Smarca4) ATPase is globally expressed at high levels during postimplantation development and its conditional ablation, beginning at gastrulation, results in increased apoptosis, growth retardation, and, ultimately, embryonic death. Global gene expression analysis revealed that genes upregulated in Rosa26CreERT2; Brg1(flox/flox) embryos (here referred to as Brg1(d/d) embryos to describe embryos with deletion of the Brg1(flox/flox) alleles) negatively regulate cell cycle progression and cell growth. In addition, the p53 (Trp53) protein, which is virtually undetectable in early wild-type embryos, accumulated in the Brg1(d/d) embryos and activated the p53-dependent pathways. Using P19 cells, we show that Brg1 and CHD4 (chromodomain helicase DNA binding protein 4) coordinate to control target gene expression. Both proteins physically interact and show a substantial overlap of binding sites at chromatin accessible regions adjacent to genes differentially expressed in the Brg1(d/d) embryos. Specifically, Brg1 deficiency results in reduced levels of the repressive histone H3 lysine K27 trimethylation (H3K27me3) histone mark and an increase in the amount of open chromatin at the regulatory region of the p53 and p21 (Cdkn1a) genes. These results provide insights into the mechanisms by which Brg1 functions, which is in part via the p53 program, to constrain gene expression and facilitate rapid embryonic growth. PMID- 27185877 TI - Heregulin/ErbB3 Signaling Enhances CXCR4-Driven Rac1 Activation and Breast Cancer Cell Motility via Hypoxia-Inducible Factor 1alpha. AB - The growth factor heregulin (HRG), a ligand of ErbB3 and ErbB4 receptors, contributes to breast cancer development and the promotion of metastatic disease, and its expression in breast tumors has been associated with poor clinical outcome and resistance to therapy. In this study, we found that breast cancer cells exposed to sustained HRG treatment show markedly enhanced Rac1 activation and migratory activity in response to the CXCR4 ligand SDF-1/CXCL12, effects mediated by P-Rex1, a Rac-guanine nucleotide exchange factor (GEF) aberrantly expressed in breast cancer. Notably, HRG treatment upregulates surface expression levels of CXCR4, a G protein-coupled receptor (GPCR) implicated in breast cancer metastasis and an indicator of poor prognosis in breast cancer patients. A detailed mechanistic analysis revealed that CXCR4 upregulation and sensitization of the Rac response/motility by HRG are mediated by the transcription factor hypoxia-inducible factor 1alpha (HIF-1alpha) via ErbB3 and independently of ErbB4. HRG caused prominent induction in the nuclear expression of HIF-1alpha, which transcriptionally activates the CXCR4 gene via binding to a responsive element located in positions -1376 to -1372 in the CXCR4 promoter, as revealed by mutagenesis analysis and chromatin immunoprecipitation (ChIP). Our results uncovered a novel function for ErbB3 in enhancing breast cancer cell motility and sensitization of the P-Rex1/Rac1 pathway through HIF-1alpha-mediated transcriptional induction of CXCR4. PMID- 27185876 TI - Berardinelli-Seip Congenital Lipodystrophy 2/Seipin Is Not Required for Brown Adipogenesis but Regulates Brown Adipose Tissue Development and Function. AB - Brown adipose tissue (BAT) plays a unique role in regulating whole-body energy homeostasis by dissipating energy through thermogenic uncoupling. Berardinelli Seip congenital lipodystrophy (BSCL) type 2 (BSCL2; also known as seipin) is a lipodystrophy-associated endoplasmic reticulum membrane protein essential for white adipocyte differentiation. Whether BSCL2 directly participates in brown adipocyte differentiation, development, and function, however, is unknown. We show that BSCL2 expression is increased during brown adipocyte differentiation. Its deletion does not impair the classic brown adipogenic program but rather induces premature activation of differentiating brown adipocytes through cyclic AMP (cAMP)/protein kinase A (PKA)-mediated lipolysis and fatty acid and glucose oxidation, as well as uncoupling. cAMP/PKA signaling is physiologically activated during neonatal BAT development in wild-type mice and greatly potentiated in mice with genetic deletion of Bscl2 in brown progenitor cells, leading to reduced BAT mass and lipid content during neonatal brown fat formation. However, prolonged overactivation of cAMP/PKA signaling during BAT development ultimately causes apoptosis of brown adipocytes through inflammation, resulting in BAT atrophy and increased overall adiposity in adult mice. These findings reveal a key cell autonomous role for BSCL2 in controlling BAT mass/activity and provide novel insights into therapeutic strategies targeting cAMP/PKA signaling to regulate brown adipocyte function, viability, and metabolic homeostasis. PMID- 27185878 TI - Novel MicroRNA Regulators of Atrial Natriuretic Peptide Production. AB - Atrial natriuretic peptide (ANP) has a central role in regulating blood pressure in humans. Recently, microRNA 425 (miR-425) was found to regulate ANP production by binding to the mRNA of NPPA, the gene encoding ANP. mRNAs typically contain multiple predicted microRNA (miRNA)-binding sites, and binding of different miRNAs may independently or coordinately regulate the expression of any given mRNA. We used a multifaceted screening strategy that integrates bioinformatics, next-generation sequencing data, human genetic association data, and cellular models to identify additional functional NPPA-targeting miRNAs. Two novel miRNAs, miR-155 and miR-105, were found to modulate ANP production in human cardiomyocytes and target genetic variants whose minor alleles are associated with higher human plasma ANP levels. Both miR-155 and miR-105 repressed NPPA mRNA in an allele-specific manner, with the minor allele of each respective variant conferring resistance to the miRNA either by disruption of miRNA base pairing or by creation of wobble base pairing. Moreover, miR-155 enhanced the repressive effects of miR-425 on ANP production in human cardiomyocytes. Our study combines computational, genomic, and cellular tools to identify novel miRNA regulators of ANP production that could be targeted to raise ANP levels, which may have applications for the treatment of hypertension or heart failure. PMID- 27185879 TI - Regulation of KAT6 Acetyltransferases and Their Roles in Cell Cycle Progression, Stem Cell Maintenance, and Human Disease. AB - The lysine acetyltransferase 6 (KAT6) histone acetyltransferase (HAT) complexes are highly conserved from yeast to higher organisms. They acetylate histone H3 and other nonhistone substrates and are involved in cell cycle regulation and stem cell maintenance. In addition, the human KAT6 HATs are recurrently mutated in leukemia and solid tumors. Therefore, it is important to understand the mechanisms underlying the regulation of KAT6 HATs and their roles in cell cycle progression. In this minireview, we summarize the identification and analysis of the KAT6 complexes and discuss the regulatory mechanisms governing their enzymatic activities and substrate specificities. We further focus on the roles of KAT6 HATs in regulating cell proliferation and stem cell maintenance and review recent insights that aid in understanding their involvement in human diseases. PMID- 27185880 TI - Occludin S471 Phosphorylation Contributes to Epithelial Monolayer Maturation. AB - Multiple organ systems require epithelial barriers for normal function, and barrier loss is a hallmark of diseases ranging from inflammation to epithelial cancers. However, the molecular processes regulating epithelial barrier maturation are not fully elucidated. After contact, epithelial cells undergo size reductive proliferation and differentiate, creating a dense, highly ordered monolayer with high resistance barriers. We provide evidence that the tight junction protein occludin contributes to the regulation of epithelial cell maturation upon phosphorylation of S471 in its coiled-coil domain. Overexpression of a phosphoinhibitory occludin S471A mutant prevents size-reductive proliferation and subsequent tight junction maturation in a dominant manner. Inhibition of cell proliferation in cell-contacted but immature monolayers recapitulated this phenotype. A kinase screen identified G-protein-coupled receptor kinases (GRKs) targeting S471, and GRK inhibitors delayed epithelial packing and junction maturation. We conclude that occludin contributes to the regulation of size-reductive proliferation and epithelial cell maturation in a phosphorylation-dependent manner. PMID- 27185881 TI - Determinants of Sir2-Mediated, Silent Chromatin Cohesion. AB - Cohesin associates with distinct sites on chromosomes to mediate sister chromatid cohesion. Single cohesin complexes are thought to bind by encircling both sister chromatids in a topological embrace. Transcriptionally repressed chromosomal domains in the yeast Saccharomyces cerevisiae represent specialized sites of cohesion where cohesin binds silent chromatin in a Sir2-dependent fashion. In this study, we investigated the molecular basis for Sir2-mediated cohesion. We identified a cluster of charged surface residues of Sir2, collectively termed the EKDK motif, that are required for cohesin function. In addition, we demonstrated that Esc8, a Sir2-interacting factor, is also required for silent chromatin cohesion. Esc8 was previously shown to associate with Isw1, the enzymatic core of ISW1 chromatin remodelers, to form a variant of the ISW1a chromatin remodeling complex. When ESC8 was deleted or the EKDK motif was mutated, cohesin binding at silenced chromatin domains persisted but cohesion of the domains was abolished. The data are not consistent with cohesin embracing both sister chromatids within silent chromatin domains. Transcriptional silencing remains largely intact in strains lacking ESC8 or bearing EKDK mutations, indicating that silencing and cohesion are separable functions of Sir2 and silent chromatin. PMID- 27185882 TI - Nitric Oxide Suppresses beta-Cell Apoptosis by Inhibiting the DNA Damage Response. AB - Nitric oxide, produced in pancreatic beta cells in response to proinflammatory cytokines, plays a dual role in the regulation of beta-cell fate. While nitric oxide induces cellular damage and impairs beta-cell function, it also promotes beta-cell survival through activation of protective pathways that promote beta cell recovery. In this study, we identify a novel mechanism in which nitric oxide prevents beta-cell apoptosis by attenuating the DNA damage response (DDR). Nitric oxide suppresses activation of the DDR (as measured by gammaH2AX formation and the phosphorylation of KAP1 and p53) in response to multiple genotoxic agents, including camptothecin, H2O2, and nitric oxide itself, despite the presence of DNA damage. While camptothecin and H2O2 both induce DDR activation, nitric oxide suppresses only camptothecin-induced apoptosis and not H2O2-induced necrosis. The ability of nitric oxide to suppress the DDR appears to be selective for pancreatic beta cells, as nitric oxide fails to inhibit DDR signaling in macrophages, hepatocytes, and fibroblasts, three additional cell types examined. While originally described as the damaging agent responsible for cytokine-induced beta-cell death, these studies identify a novel role for nitric oxide as a protective molecule that promotes beta-cell survival by suppressing DDR signaling and attenuating DNA damage-induced apoptosis. PMID- 27185884 TI - Using the Ubiquitin-modified Proteome to Monitor Distinct and Spatially Restricted Protein Homeostasis Dysfunction. AB - Protein homeostasis dysfunction has been implicated in the development and progression of aging related human pathologies. There is a need for the establishment of quantitative methods to evaluate global protein homoeostasis function. As the ubiquitin (ub) proteasome system plays a key role in regulating protein homeostasis, we applied quantitative proteomic methods to evaluate the sensitivity of site-specific ubiquitylation events as markers for protein homeostasis dysfunction. Here, we demonstrate that the ub-modified proteome can exceed the sensitivity of engineered fluorescent reporters as a marker for proteasome dysfunction and can provide unique signatures for distinct proteome challenges which is not possible with engineered reporters. We demonstrate that combining ub-proteomics with subcellular fractionation can effectively separate degradative and regulatory ubiquitylation events on distinct protein populations. Using a recently developed potent inhibitor of the critical protein homeostasis factor p97/VCP, we demonstrate that distinct insults to protein homeostasis function can elicit robust and largely unique alterations to the ub-modified proteome. Taken together, we demonstrate that proteomic approaches to monitor the ub-modified proteome can be used to evaluate global protein homeostasis and can be used to monitor distinct functional outcomes for spatially separated protein populations. PMID- 27185886 TI - Bromodeoxyuridine does not contribute to sister chromatid exchange events in normal or Bloom syndrome cells. AB - Sister chromatid exchanges (SCEs) are considered sensitive indicators of genome instability. Detection of SCEs typically requires cells to incorporate bromodeoxyuridine (BrdU) during two rounds of DNA synthesis. Previous studies have suggested that SCEs are induced by DNA replication over BrdU-substituted DNA and that BrdU incorporation alone could be responsible for the high number of SCE events observed in cells from patients with Bloom syndrome (BS), a rare genetic disorder characterized by marked genome instability and high SCE frequency. Here we show using Strand-seq, a single cell DNA template strand sequencing technique, that the presence of variable BrdU concentrations in the cell culture medium and in DNA template strands has no effect on SCE frequency in either normal or BS cells. We conclude that BrdU does not induce SCEs and that SCEs detected in either normal or BS cells reflect DNA repair events that occur spontaneously. PMID- 27185885 TI - G-rich telomeric and ribosomal DNA sequences from the fission yeast genome form stable G-quadruplex DNA structures in vitro and are unwound by the Pfh1 DNA helicase. AB - Certain guanine-rich sequences have an inherent propensity to form G-quadruplex (G4) structures. G4 structures are e.g. involved in telomere protection and gene regulation. However, they also constitute obstacles during replication if they remain unresolved. To overcome these threats to genome integrity, organisms harbor specialized G4 unwinding helicases. In Schizosaccharomyces pombe, one such candidate helicase is Pfh1, an evolutionarily conserved Pif1 homolog. Here, we addressed whether putative G4 sequences in S. pombe can adopt G4 structures and, if so, whether Pfh1 can resolve them. We tested two G4 sequences, derived from S. pombe ribosomal and telomeric DNA regions, and demonstrated that they form inter- and intramolecular G4 structures, respectively. Also, Pfh1 was enriched in vivo at the ribosomal G4 DNA and telomeric sites. The nuclear isoform of Pfh1 (nPfh1) unwound both types of structure, and although the G4-stabilizing compound Phen DC3 significantly enhanced their stability, nPfh1 still resolved them efficiently. However, stable G4 structures significantly inhibited adenosine triphosphate hydrolysis by nPfh1. Because ribosomal and telomeric DNA contain putative G4 regions conserved from yeasts to humans, our studies support the important role of G4 structure formation in these regions and provide further evidence for a conserved role for Pif1 helicases in resolving G4 structures. PMID- 27185887 TI - Mutational analysis of the Potyviridae transcriptional slippage site utilized for expression of the P3N-PIPO and P1N-PISPO proteins. AB - The Potyviridae comprise the largest and most important family of RNA plant viruses. An essential overlapping ORF, termed pipo, resides in an internal region of the main polyprotein ORF. Recently, expression of pipo was shown to depend on programmed transcriptional slippage at a conserved GAAAAAA sequence, resulting in the insertion of an extra A into a proportion of viral transcripts, fusing the pipo ORF in frame with the 5' third of the polyprotein ORF. However, the sequence features that mediate slippage have not been characterized. Using a duplicate copy of the pipo slip site region fused into a different genomic location where it can be freely mutated, we investigated the sequence requirements for transcriptional slippage. We find that the leading G is not strictly required, but increased flanking sequence GC content correlates with higher insertion rates. A homopolymeric hexamer is optimal for producing mainly single-nucleotide insertions. We also identify an overabundance of G to A substitutions immediately 3'-adjacent to GAAAAAA in insertion-free transcripts, which we infer to result from a 'to-fro' form of slippage during positive-strand synthesis. Analysis of wild-type and reverse complement sequences suggests that slippage occurs preferentially during synthesis of poly(A) and therefore occurs mainly during positive-strand synthesis. PMID- 27185888 TI - In vivo evidence for translesion synthesis by the replicative DNA polymerase delta. AB - The intolerance of DNA polymerase delta (Poldelta) to incorrect base pairing contributes to its extremely high accuracy during replication, but is believed to inhibit translesion synthesis (TLS). However, chicken DT40 cells lacking the POLD3 subunit of Poldelta are deficient in TLS. Previous genetic and biochemical analysis showed that POLD3 may promote lesion bypass by Poldelta itself independently of the translesion polymerase Polzeta of which POLD3 is also a subunit. To test this hypothesis, we have inactivated Poldelta proofreading in pold3 cells. This significantly restored TLS in pold3 mutants, enhancing dA incorporation opposite abasic sites. Purified proofreading-deficient human Poldelta holoenzyme performs TLS of abasic sites in vitro much more efficiently than the wild type enzyme, with over 90% of TLS events resulting in dA incorporation. Furthermore, proofreading deficiency enhances the capability of Poldelta to continue DNA synthesis over UV lesions both in vivo and in vitro These data support Poldelta contributing to TLS in vivo and suggest that the mutagenesis resulting from loss of Poldelta proofreading activity may in part be explained by enhanced lesion bypass. PMID- 27185889 TI - CTLPScanner: a web server for chromothripsis-like pattern detection. AB - Chromothripsis is a recently observed phenomenon in cancer cells in which one or several chromosomes shatter into pieces with subsequent inaccurate reassembly and clonal propagation. This type of event generates a potentially vast number of mutations within a relatively short-time period, and has been considered as a new paradigm in cancer development. Despite recent advances, much work is still required to better understand the molecular mechanisms of this phenomenon, and thus an easy-to-use tool is in urgent need for automatically detecting and annotating chromothripsis. Here we present CTLPScanner, a web server for detection of chromothripsis-like pattern (CTLP) in genomic array data. The output interface presents intuitive graphical representations of detected chromosome pulverization region, as well as detailed results in table format. CTLPScanner also provides additional information for associated genes in chromothripsis region to help identify the potential candidates involved in tumorigenesis. To assist in performing meta-data analysis, we integrated over 50 000 pre-processed genomic arrays from The Cancer Genome Atlas and Gene Expression Omnibus into CTLPScanner. The server allows users to explore the presence of chromothripsis signatures from public data resources, without carrying out any local data processing. CTLPScanner is freely available at http://cgma.scu.edu.cn/CTLPScanner/. PMID- 27185892 TI - 3D-GNOME: an integrated web service for structural modeling of the 3D genome. AB - Recent advances in high-throughput chromosome conformation capture (3C) technology, such as Hi-C and ChIA-PET, have demonstrated the importance of 3D genome organization in development, cell differentiation and transcriptional regulation. There is now a widespread need for computational tools to generate and analyze 3D structural models from 3C data. Here we introduce our 3D GeNOme Modeling Engine (3D-GNOME), a web service which generates 3D structures from 3C data and provides tools to visually inspect and annotate the resulting structures, in addition to a variety of statistical plots and heatmaps which characterize the selected genomic region. Users submit a bedpe (paired-end BED format) file containing the locations and strengths of long range contact points, and 3D-GNOME simulates the structure and provides a convenient user interface for further analysis. Alternatively, a user may generate structures using published ChIA-PET data for the GM12878 cell line by simply specifying a genomic region of interest. 3D-GNOME is freely available at http://3dgnome.cent.uw.edu.pl/. PMID- 27185891 TI - Mapping DNA polymerase errors by single-molecule sequencing. AB - Genomic integrity is compromised by DNA polymerase replication errors, which occur in a sequence-dependent manner across the genome. Accurate and complete quantification of a DNA polymerase's error spectrum is challenging because errors are rare and difficult to detect. We report a high-throughput sequencing assay to map in vitro DNA replication errors at the single-molecule level. Unlike previous methods, our assay is able to rapidly detect a large number of polymerase errors at base resolution over any template substrate without quantification bias. To overcome the high error rate of high-throughput sequencing, our assay uses a barcoding strategy in which each replication product is tagged with a unique nucleotide sequence before amplification. This allows multiple sequencing reads of the same product to be compared so that sequencing errors can be found and removed. We demonstrate the ability of our assay to characterize the average error rate, error hotspots and lesion bypass fidelity of several DNA polymerases. PMID- 27185890 TI - QuadBase2: web server for multiplexed guanine quadruplex mining and visualization. AB - DNA guanine quadruplexes or G4s are non-canonical DNA secondary structures which affect genomic processes like replication, transcription and recombination. G4s are computationally identified by specific nucleotide motifs which are also called putative G4 (PG4) motifs. Despite the general relevance of these structures, there is currently no tool available that can allow batch queries and genome-wide analysis of these motifs in a user-friendly interface. QuadBase2 (quadbase.igib.res.in) presents a completely reinvented web server version of previously published QuadBase database. QuadBase2 enables users to mine PG4 motifs in up to 178 eukaryotes through the EuQuad module. This module interfaces with Ensembl Compara database, to allow users mine PG4 motifs in the orthologues of genes of interest across eukaryotes. PG4 motifs can be mined across genes and their promoter sequences in 1719 prokaryotes through ProQuad module. This module includes a feature that allows genome-wide mining of PG4 motifs and their visualization as circular histograms. TetraplexFinder, the module for mining PG4 motifs in user-provided sequences is now capable of handling up to 20 MB of data. QuadBase2 is a comprehensive PG4 motif mining tool that further expands the configurations and algorithms for mining PG4 motifs in a user-friendly way. PMID- 27185893 TI - incaRNAfbinv: a web server for the fragment-based design of RNA sequences. AB - In recent years, new methods for computational RNA design have been developed and applied to various problems in synthetic biology and nanotechnology. Lately, there is considerable interest in incorporating essential biological information when solving the inverse RNA folding problem. Correspondingly, RNAfbinv aims at including biologically meaningful constraints and is the only program to-date that performs a fragment-based design of RNA sequences. In doing so it allows the design of sequences that do not necessarily exactly fold into the target, as long as the overall coarse-grained tree graph shape is preserved. Augmented by the weighted sampling algorithm of incaRNAtion, our web server called incaRNAfbinv implements the method devised in RNAfbinv and offers an interactive environment for the inverse folding of RNA using a fragment-based design approach. It takes as input: a target RNA secondary structure; optional sequence and motif constraints; optional target minimum free energy, neutrality and GC content. In addition to the design of synthetic regulatory sequences, it can be used as a pre processing step for the detection of novel natural occurring RNAs. The two complementary methodologies RNAfbinv and incaRNAtion are merged together and fully implemented in our web server incaRNAfbinv, available at http://www.cs.bgu.ac.il/incaRNAfbinv. PMID- 27185894 TI - CHOPCHOP v2: a web tool for the next generation of CRISPR genome engineering. AB - In just 3 years CRISPR genome editing has transformed biology, and its popularity and potency continue to grow. New CRISPR effectors and rules for locating optimum targets continue to be reported, highlighting the need for computational CRISPR targeting tools to compile these rules and facilitate target selection and design. CHOPCHOP is one of the most widely used web tools for CRISPR- and TALEN based genome editing. Its overarching principle is to provide an intuitive and powerful tool that can serve both novice and experienced users. In this major update we introduce tools for the next generation of CRISPR advances, including Cpf1 and Cas9 nickases. We support a number of new features that improve the targeting power, usability and efficiency of CHOPCHOP. To increase targeting range and specificity we provide support for custom length sgRNAs, and we evaluate the sequence composition of the whole sgRNA and its surrounding region using models compiled from multiple large-scale studies. These and other new features, coupled with an updated interface for increased usability and support for a continually growing list of organisms, maintain CHOPCHOP as one of the leading tools for CRISPR genome editing. CHOPCHOP v2 can be found at http://chopchop.cbu.uib.no. PMID- 27185896 TI - iPARTS2: an improved tool for pairwise alignment of RNA tertiary structures, version 2. AB - Since its first release in 2010, iPARTS has become a valuable tool for globally or locally aligning two RNA 3D structures. It was implemented by a structural alphabet (SA)-based approach, which uses an SA of 23 letters to reduce RNA 3D structures into 1D sequences of SA letters and applies traditional sequence alignment to these SA-encoded sequences for determining their global or local similarity. In this version, we have re-implemented iPARTS into a new web server iPARTS2 by constructing a totally new SA, which consists of 92 elements with each carrying both information of base and backbone geometry for a representative nucleotide. This SA is significantly different from the one used in iPARTS, because the latter consists of only 23 elements with each carrying only the backbone geometry information of a representative nucleotide. Our experimental results have shown that iPARTS2 outperforms its previous version iPARTS and also achieves better accuracy than other popular tools, such as SARA, SETTER and RASS, in RNA alignment quality and function prediction. iPARTS2 takes as input two RNA 3D structures in the PDB format and outputs their global or local alignments with graphical display. iPARTS2 is now available online at http://genome.cs.nthu.edu.tw/iPARTS2/. PMID- 27185895 TI - Alternative splicing affects the subcellular localization of Drosha. AB - The RNase III enzyme Drosha is a key factor in microRNA (miRNA) biogenesis and as such indispensable for cellular homeostasis and developmental processes. Together with its co-factor DGCR8, it converts the primary transcript (pri-miRNA) into the precursor hairpin (pre-miRNA) in the nucleus. While the middle and the C-terminal domain are crucial for pri-miRNA processing and DGCR8 binding, the function of the N-terminus remains cryptic. Different studies have linked this region to the subcellular localization of Drosha, stabilization and response to stress. In this study, we identify alternatively spliced Drosha transcripts that are devoid of a part of the arginine/serine-rich (RS-rich) domain and expressed in a large set of human cells. In contrast to their expected habitation, we find two isoforms also present in the cytoplasm, while the other two isoforms reside exclusively in the nucleus. Their processing activity for pri-miRNAs and the binding to co-factors remains unaltered. In multiple cell lines, the endogenous mRNA expression of the Drosha isoforms correlates with the localization of endogenous Drosha proteins. The pri-miRNA processing efficiency is not significantly different between groups of cells with or without cytoplasmic Drosha expression. In summary, we discovered novel isoforms of Drosha with differential subcellular localization pointing toward additional layers of complexity in the regulation of its activity. PMID- 27185897 TI - Combined PET/MRI: Multimodality insights into acute stroke hemodynamics. PMID- 27185898 TI - Thalamic amnesia after infarct: The role of the mammillothalamic tract and mediodorsal nucleus. PMID- 27185899 TI - Blowing the whistle on sports concussions: Will the risk of dementia change the game? PMID- 27185900 TI - Journal Club: Time trends in incidence, case fatality, and mortality of intracerebral hemorrhage. PMID- 27185901 TI - Clinical Reasoning: Heart to swallow. PMID- 27185902 TI - Teaching NeuroImages: Limbic encephalitis associated with relapsing polychondritis. PMID- 27185903 TI - Combination Nicotine Metered Dose Inhaler and Nicotine Patch for Smoking Cessation: A Randomized Controlled Trial. AB - INTRODUCTION: In order to replicate the rewarding effects of smoking, nicotine replacement therapies must deliver nicotine via the pulmonary route. We aimed to measure the efficacy of a simple pressurized metered dose inhaler containing nicotine combined with a nicotine patch for smoking cessation. METHODS: Double blind randomized placebo-controlled, parallel group trial conducted at the University of Otago, Wellington, New Zealand. Five-hundred two adults (>=18 years) who smoked at least nine cigarettes per day, with a Fagerstrom Test for Nicotine Dependence >=3 who wanted to quit, were randomized (1:1). INTERVENTIONS: active nicotine pressurized metered dose inhaler (pMDI) plus active nicotine patch, versus placebo pMDI plus active nicotine patch. Subjects were instructed to use the aerosols for 6 months when they felt an urge to smoke and the patches daily for 5 months, reduce their smoking and quit by the end of the fourth week. Subjects were followed for 7 months. The primary outcome was prolonged 6 month not smoked on 7 consecutive days, analyzed by intention-to-treat. RESULTS: For the primary outcome, 78/246 (31.71%) in the active group versus 46/256 (17.97%) in the control group were abstinent (odds ratio 2.12, 95% confidence interval 1.40 to 3.23). Adverse events were reported by 245/246 (99.6%) and 247/256 (96.5%) subjects in the active and control groups, respectively. Mild coughing which decreased with regular use was common with the nicotine aerosols. CONCLUSION: Inhaled nicotine from a metered dose inhaler combined with a nicotine patch substantially improves abstinence for 6 months amongst adult nicotine dependant smokers wanting to quit. IMPLICATIONS: In 2012, we published a systematic review of the use nicotine by inhalation in this journal. At that time we were unable to find any studies that had measured the effects of nicotine delivery by pMDI on smoking cessation, and we are not aware of any since 2012. Our study is the first to look at nicotine by pMDI in smoking cessation. The present trial demonstrates that a simple nonproprietary nicotine inhaler, using relatively inexpensive standard technology, increases smoking cessation rates over and above nicotine patch therapy, and could usefully enhance nicotine replacement in smoking cessation treatment. PMID- 27185904 TI - Does high muscle temperature accentuate skeletal muscle injury from eccentric exercise? AB - Hyperthermia is suspected of accentuating skeletal muscle injury from novel exercise, but this has not been well studied. This study examined if high muscle temperatures alters skeletal muscle injury induced by eccentric exercise (ECC). Eight volunteers (age, 22.5 +/- 4.1 year; height, 169.5 +/- 10.8 cm; body mass, 76.2 +/- 12.6 kg), serving as their own control, and who were not heat acclimatized, completed two elbow flexor ECC trials; in one trial the biceps were heated >40 degrees C (HEAT) and in the other trial there was no heating (NON). HEAT was applied with shortwave diathermy (100 W) for 15 min immediately before the first ECC bout and for 2 min in between each bout. Individuals were followed for 10 days after each ECC session, with a 6-week washout period between arms. The maximal voluntary isometric contraction decreased by 41 +/- 17% and 46 +/- 20% in the NON and HEAT trials, respectively. Bicep circumference increased by 0.07 +/- 0.08 mm (4%, P = 0.04) and relaxed range of motion decreased by 11.5 +/- 8.2 degrees (30%, P < 0.001) in both trials. Serum creatine kinase peaked 72-h following ECC (NON: 6289 +/- 10407; HEAT: 5486 +/- 6229 IU L(-1), 38-fold increase, P < 0.01) as did serum myoglobin (NON: 362 +/- 483; HEAT: 355 +/- 373 MUg L(-1), 13-fold increase, P < 0.03). Plasma HSP 70 was higher (P < 0.02) in HEAT after 120-h of recovery. There were no differences between treatments for plasma HSP27 and interleukins 1beta, 6, and 10. The results indicate that >40 degrees C muscle temperature does not alter skeletal muscle injury or functional impairments induced by novel ECC. PMID- 27185905 TI - Dietary salt regulates uroguanylin expression and signaling activity in the kidney, but not in the intestine. AB - The peptide uroguanylin (Ugn) is expressed at significant levels only in intestine and kidney, and is stored in both tissues primarily (perhaps exclusively) as intact prouroguanylin (proUgn). Intravascular infusion of either Ugn or proUgn evokes well-characterized natriuretic responses in rodents. Furthermore, Ugn knockout mice display hypertension and salt handling deficits, indicating that the Na(+) excretory mechanisms triggered when the peptides are infused into anesthetized animals are likely to operate under normal physiological conditions, and contribute to electrolyte homeostasis in conscious animals. Here, we provide strong corroborative evidence for this hypothesis, by demonstrating that UU gnV (the rate of urinary Ugn excretion) approximately doubled in conscious, unrestrained rats consuming a high-salt diet, and decreased by ~15% after salt restriction. These changes in UU gnV were not associated with altered plasma proUgn levels (shown here to be an accurate index of intestinal proUgn secretion). Furthermore, enteric Ugn mRNA levels were unaffected by salt intake, whereas renal Ugn mRNA levels increased sharply during periods of increased dietary salt consumption. Together, these data suggest that diet-evoked Ugn signals originate within the kidney, rather than the intestine, thus strengthening a growing body of evidence against a widely cited hypothesis that Ugn serves as the mediator of an entero-renal natriuretic signaling axis, while underscoring a likely intrarenal natriuretic role for the peptide. The data further suggest that intrarenal Ugn signaling is preferentially engaged when salt intake is elevated, and plays only a minor role when salt intake is restricted. PMID- 27185906 TI - Skeletal muscle IL-6 and regulation of liver metabolism during high-fat diet and exercise training. AB - Interleukin (IL)-6 is released from skeletal muscle (SkM) during exercise and has been shown to affect hepatic metabolism. It is, however, unknown whether SkM IL-6 is involved in the regulation of exercise training-induced counteraction of changes in carbohydrate and lipid metabolism in the liver in response to high-fat diet (HFD) feeding. Male SkM-specific IL-6 KO (MKO) and Floxed mice were subjected to Chow diet, HFD or HFD combined with exercise training (HFD ExTr) for 16 weeks. Hepatic phosphoenolpyruvate carboxykinase (PEPCK) protein content decreased with both HFD and HFD ExTr in Floxed mice, but increased in IL-6 MKO mice on HFD In addition, the intrahepatic glucose concentration was in IL-6 MKO mice higher in HFD than chow. Within HFD ExTr mice, hepatic glucose-6-phosphatase (G6Pase) 36 kDa protein content was higher in IL-6 MKO than Floxed mice. Hepatic pyruvate dehydrogenase kinase (PDK) 4 and PDK2 protein content was in Floxed mice lower in HFD ExTr than Chow. In addition, hepatic ACC1-phosphorylation was higher and ACC1 protein lower in HFD Together this suggests that SkM IL-6 regulates hepatic glucose metabolism, but does not seem to be of major importance for the regulation of oxidative capacity or lipogenesis in liver during HFD or HFD combined with exercise training. PMID- 27185907 TI - Soft, thin skin-mounted power management systems and their use in wireless thermography. AB - Power supply represents a critical challenge in the development of body integrated electronic technologies. Although recent research establishes an impressive variety of options in energy storage (batteries and supercapacitors) and generation (triboelectric, piezoelectric, thermoelectric, and photovoltaic devices), the modest electrical performance and/or the absence of soft, biocompatible mechanical properties limit their practical use. The results presented here form the basis of soft, skin-compatible means for efficient photovoltaic generation and high-capacity storage of electrical power using dual junction, compound semiconductor solar cells and chip-scale, rechargeable lithium ion batteries, respectively. Miniaturized components, deformable interconnects, optimized array layouts, and dual-composition elastomer substrates, superstrates, and encapsulation layers represent key features. Systematic studies of the materials and mechanics identify optimized designs, including unusual configurations that exploit a folded, multilayer construct to improve the functional density without adversely affecting the soft, stretchable characteristics. System-level examples exploit such technologies in fully wireless sensors for precision skin thermography, with capabilities in continuous data logging and local processing, validated through demonstrations on volunteer subjects in various realistic scenarios. PMID- 27185908 TI - Mammalian African trypanosome VSG coat enhances tsetse's vector competence. AB - Tsetse flies are biological vectors of African trypanosomes, the protozoan parasites responsible for causing human and animal trypanosomiases across sub Saharan Africa. Currently, no vaccines are available for disease prevention due to antigenic variation of the Variant Surface Glycoproteins (VSG) that coat parasites while they reside within mammalian hosts. As a result, interference with parasite development in the tsetse vector is being explored to reduce disease transmission. A major bottleneck to infection occurs as parasites attempt to colonize tsetse's midgut. One critical factor influencing this bottleneck is the fly's peritrophic matrix (PM), a semipermeable, chitinous barrier that lines the midgut. The mechanisms that enable trypanosomes to cross this barrier are currently unknown. Here, we determined that as parasites enter the tsetse's gut, VSG molecules released from trypanosomes are internalized by cells of the cardia the tissue responsible for producing the PM. VSG internalization results in decreased expression of a tsetse microRNA (mir-275) and interferes with the Wnt signaling pathway and the Iroquois/IRX transcription factor family. This interference reduces the function of the PM barrier and promotes parasite colonization of the gut early in the infection process. Manipulation of the insect midgut homeostasis by the mammalian parasite coat proteins is a novel function and indicates that VSG serves a dual role in trypanosome biology-that of facilitating transmission through its mammalian host and insect vector. We detail critical steps in the course of trypanosome infection establishment that can serve as novel targets to reduce the tsetse's vector competence and disease transmission. PMID- 27185909 TI - LAP-like process as an immune mechanism downstream of IFN-gamma in control of the human malaria Plasmodium vivax liver stage. AB - IFN-gamma is a major regulator of immune functions and has been shown to induce liver-stage Plasmodium elimination both in vitro and in vivo. The molecular mechanism responsible for the restriction of liver-stage Plasmodium downstream of IFN-gamma remains uncertain, however. Autophagy, a newly described immune defense mechanism, was recently identified as a downstream pathway activated in response to IFN-gamma in the control of intracellular infections. We thus hypothesized that the killing of liver-stage malarial parasites by IFN-gamma involves autophagy induction. Our results show that whereas IFN-gamma treatment of human hepatocytes activates autophagy, the IFN-gamma-mediated restriction of liver stage Plasmodium vivax depends only on the downstream autophagy-related proteins Beclin 1, PI3K, and ATG5, but not on the upstream autophagy-initiating protein ULK1. In addition, IFN-gamma enhanced the recruitment of LC3 onto the parasitophorous vacuole membrane (PVM) and increased the colocalization of lysosomal vesicles with P. vivax compartments. Taken together, these data indicate that IFN-gamma mediates the control of liver-stage P. vivax by inducing a noncanonical autophagy pathway resembling that of LC3-associated phagocytosis, in which direct decoration of the PVM with LC3 promotes the fusion of P. vivax compartments with lysosomes and subsequent killing of the pathogen. Understanding the hepatocyte response to IFN-gamma during Plasmodium infection and the roles of autophagy-related proteins may provide an urgently needed alternative strategy for the elimination of this human malaria. PMID- 27185910 TI - Resistance to docetaxel in prostate cancer is associated with androgen receptor activation and loss of KDM5D expression. AB - The androgen receptor (AR) plays an essential role in prostate cancer, and suppression of its signaling with androgen deprivation therapy (ADT) has been the mainstay of treatment for metastatic hormone-sensitive prostate cancer for more than 70 y. Chemotherapy has been reserved for metastatic castration-resistant prostate cancer (mCRPC). The Eastern Cooperative Oncology Group-led trial E3805: ChemoHormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) showed that the addition of docetaxel to ADT prolonged overall survival compared with ADT alone in patients with metastatic hormone-sensitive prostate cancer. This finding suggests that there is an interaction between AR signaling activity and docetaxel sensitivity. Here we demonstrate that the prostate cancer cell lines LNCaP and LAPC4 display markedly different sensitivity to docetaxel with AR activation, and RNA-seq analysis of these cell lines identified KDM5D (lysine-specific demethylase 5D) encoded on the Y chromosome as a potential mediator of this sensitivity. Knocking down KDM5D expression in LNCaP leads to docetaxel resistance in the presence of dihydrotestosterone. KDM5D physically interacts with AR in the nucleus, and regulates its transcriptional activity by demethylating H3K4me3 active transcriptional marks. Attenuating KDM5D expression dysregulates AR signaling, resulting in docetaxel insensitivity. KDM5D deletion was also observed in the LNCaP-derived CRPC cell line 104R2, which displayed docetaxel insensitivity with AR activation, unlike parental LNCaP. Dataset analysis from the Oncomine database revealed significantly decreased KDM5D expression in CRPC and poorer prognosis with low KDM5D expression. Taking these data together, this work indicates that KDM5D modulates the AR axis and that this is associated with altered docetaxel sensitivity. PMID- 27185911 TI - Empirical redefinition of comprehensive health and well-being in the older adults of the United States. AB - The World Health Organization (WHO) defines health as a "state of complete physical, mental and social well-being and not merely the absence of disease or infirmity." Despite general acceptance of this comprehensive definition, there has been little rigorous scientific attempt to use it to measure and assess population health. Instead, the dominant model of health is a disease-centered Medical Model (MM), which actively ignores many relevant domains. In contrast to the MM, we approach this issue through a Comprehensive Model (CM) of health consistent with the WHO definition, giving statistically equal consideration to multiple health domains, including medical, physical, psychological, functional, and sensory measures. We apply a data-driven latent class analysis (LCA) to model 54 specific health variables from the National Social Life, Health, and Aging Project (NSHAP), a nationally representative sample of US community-dwelling older adults. We first apply the LCA to the MM, identifying five health classes differentiated primarily by having diabetes and hypertension. The CM identifies a broader range of six health classes, including two "emergent" classes completely obscured by the MM. We find that specific medical diagnoses (cancer and hypertension) and health behaviors (smoking) are far less important than mental health (loneliness), sensory function (hearing), mobility, and bone fractures in defining vulnerable health classes. Although the MM places two-thirds of the US population into "robust health" classes, the CM reveals that one-half belong to less healthy classes, independently associated with higher mortality. This reconceptualization has important implications for medical care delivery, preventive health practices, and resource allocation. PMID- 27185912 TI - Coronavirus receptor switch explained from the stereochemistry of protein carbohydrate interactions and a single mutation. AB - Hemagglutinin-esterases (HEs) are bimodular envelope proteins of orthomyxoviruses, toroviruses, and coronaviruses with a carbohydrate-binding "lectin" domain appended to a receptor-destroying sialate-O-acetylesterase ("esterase"). In concert, these domains facilitate dynamic virion attachment to cell-surface sialoglycans. Most HEs (type I) target 9-O-acetylated sialic acids (9-O-Ac-Sias), but one group of coronaviruses switched to using 4-O-Ac-Sias instead (type II). This specificity shift required quasisynchronous adaptations in the Sia-binding sites of both lectin and esterase domains. Previously, a partially disordered crystal structure of a type II HE revealed how the shift in lectin ligand specificity was achieved. How the switch in esterase substrate specificity was realized remained unresolved, however. Here, we present a complete structure of a type II HE with a receptor analog in the catalytic site and identify the mutations underlying the 9-O- to 4-O-Ac-Sia substrate switch. We show that (i) common principles pertaining to the stereochemistry of protein carbohydrate interactions were at the core of the transition in lectin ligand and esterase substrate specificity; (ii) in consequence, the switch in O-Ac-Sia specificity could be readily accomplished via convergent intramolecular coevolution with only modest architectural changes in lectin and esterase domains; and (iii) a single, inconspicuous Ala-to-Ser substitution in the catalytic site was key to the emergence of the type II HEs. Our findings provide fundamental insights into how proteins "see" sugars and how this affects protein and virus evolution. PMID- 27185914 TI - Genetic analysis of Vibrio parahaemolyticus intestinal colonization. AB - Vibrio parahaemolyticus is the most common cause of seafood-borne gastroenteritis worldwide and a blight on global aquaculture. This organism requires a horizontally acquired type III secretion system (T3SS2) to infect the small intestine, but knowledge of additional factors that underlie V. parahaemolyticus pathogenicity is limited. We used transposon-insertion sequencing to screen for genes that contribute to viability of V. parahaemolyticus in vitro and in the mammalian intestine. Our analysis enumerated and controlled for the host infection bottleneck, enabling robust assessment of genetic contributions to in vivo fitness. We identified genes that contribute to V. parahaemolyticus colonization of the intestine independent of known virulence mechanisms in addition to uncharacterized components of T3SS2. Our study revealed that toxR, an ancestral locus in Vibrio species, is required for V. parahaemolyticus fitness in vivo and for induction of T3SS2 gene expression. The regulatory mechanism by which V. parahaemolyticus ToxR activates expression of T3SS2 resembles Vibrio cholerae ToxR regulation of distinct virulence elements acquired via lateral gene transfer. Thus, disparate horizontally acquired virulence systems have been placed under the control of this ancestral transcription factor across independently evolved human pathogens. PMID- 27185913 TI - Immunization with a heat-killed preparation of the environmental bacterium Mycobacterium vaccae promotes stress resilience in mice. AB - The prevalence of inflammatory diseases is increasing in modern urban societies. Inflammation increases risk of stress-related pathology; consequently, immunoregulatory or antiinflammatory approaches may protect against negative stress-related outcomes. We show that stress disrupts the homeostatic relationship between the microbiota and the host, resulting in exaggerated inflammation. Repeated immunization with a heat-killed preparation of Mycobacterium vaccae, an immunoregulatory environmental microorganism, reduced subordinate, flight, and avoiding behavioral responses to a dominant aggressor in a murine model of chronic psychosocial stress when tested 1-2 wk following the final immunization. Furthermore, immunization with M. vaccae prevented stress induced spontaneous colitis and, in stressed mice, induced anxiolytic or fear reducing effects as measured on the elevated plus-maze, despite stress-induced gut microbiota changes characteristic of gut infection and colitis. Immunization with M. vaccae also prevented stress-induced aggravation of colitis in a model of inflammatory bowel disease. Depletion of regulatory T cells negated protective effects of immunization with M. vaccae on stress-induced colitis and anxiety-like or fear behaviors. These data provide a framework for developing microbiome- and immunoregulation-based strategies for prevention of stress-related pathologies. PMID- 27185915 TI - Neural circuits underlying mother's voice perception predict social communication abilities in children. AB - The human voice is a critical social cue, and listeners are extremely sensitive to the voices in their environment. One of the most salient voices in a child's life is mother's voice: Infants discriminate their mother's voice from the first days of life, and this stimulus is associated with guiding emotional and social function during development. Little is known regarding the functional circuits that are selectively engaged in children by biologically salient voices such as mother's voice or whether this brain activity is related to children's social communication abilities. We used functional MRI to measure brain activity in 24 healthy children (mean age, 10.2 y) while they attended to brief (<1 s) nonsense words produced by their biological mother and two female control voices and explored relationships between speech-evoked neural activity and social function. Compared to female control voices, mother's voice elicited greater activity in primary auditory regions in the midbrain and cortex; voice-selective superior temporal sulcus (STS); the amygdala, which is crucial for processing of affect; nucleus accumbens and orbitofrontal cortex of the reward circuit; anterior insula and cingulate of the salience network; and a subregion of fusiform gyrus associated with face perception. The strength of brain connectivity between voice selective STS and reward, affective, salience, memory, and face-processing regions during mother's voice perception predicted social communication skills. Our findings provide a novel neurobiological template for investigation of typical social development as well as clinical disorders, such as autism, in which perception of biologically and socially salient voices may be impaired. PMID- 27185917 TI - Instability of Helios-deficient Tregs is associated with conversion to a T effector phenotype and enhanced antitumor immunity. AB - Expression of the transcription factor Helios by Tregs ensures stable expression of a suppressive and anergic phenotype in the face of intense inflammatory responses, whereas Helios-deficient Tregs display diminished lineage stability, reduced FoxP3 expression, and production of proinflammatory cytokines. Here we report that selective Helios deficiency within CD4 Tregs leads to enhanced antitumor immunity through induction of an unstable phenotype and conversion of intratumoral Tregs into T effector cells within the tumor microenvironment. Induction of an unstable Treg phenotype is associated with enhanced production of proinflammatory cytokines by tumor-infiltrating but not systemic Tregs and significantly delayed tumor growth. Ab-dependent engagement of Treg surface receptors that result in Helios down-regulation also promotes conversion of intratumoral but not systemic Tregs into T effector cells and leads to enhanced antitumor immunity. These findings suggest that selective instability and conversion of intratumoral CD4 Tregs through genetic or Ab-based targeting of Helios may represent an effective approach to immunotherapy. PMID- 27185916 TI - Phosphorylation of spore coat proteins by a family of atypical protein kinases. AB - The modification of proteins by phosphorylation occurs in all life forms and is catalyzed by a large superfamily of enzymes known as protein kinases. We recently discovered a family of secretory pathway kinases that phosphorylate extracellular proteins. One member, family with sequence similarity 20C (Fam20C), is the physiological Golgi casein kinase. While examining distantly related protein sequences, we observed low levels of identity between the spore coat protein H (CotH), and the Fam20C-related secretory pathway kinases. CotH is a component of the spore in many bacterial and eukaryotic species, and is required for efficient germination of spores in Bacillus subtilis; however, the mechanism by which CotH affects germination is unclear. Here, we show that CotH is a protein kinase. The crystal structure of CotH reveals an atypical protein kinase-like fold with a unique mode of ATP binding. Examination of the genes neighboring cotH in B. subtilis led us to identify two spore coat proteins, CotB and CotG, as CotH substrates. Furthermore, we show that CotH-dependent phosphorylation of CotB and CotG is required for the efficient germination of B. subtilis spores. Collectively, our results define a family of atypical protein kinases and reveal an unexpected role for protein phosphorylation in spore biology. PMID- 27185918 TI - Range expansions transition from pulled to pushed waves as growth becomes more cooperative in an experimental microbial population. AB - Range expansions are becoming more frequent due to environmental changes and rare long-distance dispersal, often facilitated by anthropogenic activities. Simple models in theoretical ecology explain many emergent properties of range expansions, such as a constant expansion velocity, in terms of organism-level properties such as growth and dispersal rates. Testing these quantitative predictions in natural populations is difficult because of large environmental variability. Here, we used a controlled microbial model system to study range expansions of populations with and without intraspecific cooperativity. For noncooperative growth, the expansion dynamics were dominated by population growth at the low-density front, which pulled the expansion forward. We found these expansions to be in close quantitative agreement with the classical theory of pulled waves by Fisher [Fisher RA (1937) Ann Eugen 7(4):355-369] and Skellam [Skellam JG (1951) Biometrika 38(1-2):196-218], suitably adapted to our experimental system. However, as cooperativity increased, the expansions transitioned to being pushed, that is, controlled by growth and dispersal in the bulk as well as in the front. Given the prevalence of cooperative growth in nature, understanding the effects of cooperativity is essential to managing invading species and understanding their evolution. PMID- 27185919 TI - On the unsupervised analysis of domain-specific Chinese texts. AB - With the growing availability of digitized text data both publicly and privately, there is a great need for effective computational tools to automatically extract information from texts. Because the Chinese language differs most significantly from alphabet-based languages in not specifying word boundaries, most existing Chinese text-mining methods require a prespecified vocabulary and/or a large relevant training corpus, which may not be available in some applications. We introduce an unsupervised method, top-down word discovery and segmentation (TopWORDS), for simultaneously discovering and segmenting words and phrases from large volumes of unstructured Chinese texts, and propose ways to order discovered words and conduct higher-level context analyses. TopWORDS is particularly useful for mining online and domain-specific texts where the underlying vocabulary is unknown or the texts of interest differ significantly from available training corpora. When outputs from TopWORDS are fed into context analysis tools such as topic modeling, word embedding, and association pattern finding, the results are as good as or better than that from using outputs of a supervised segmentation method. PMID- 27185920 TI - AtVPS41-mediated endocytic pathway is essential for pollen tube-stigma interaction in Arabidopsis. AB - In flowering plants, extensive male-female interactions are required for successful fertilization in which various signaling cascades are involved. Prevacuolar compartments (PVC) and vacuoles are two types of subcellular compartments that terminate signal transduction by sequestrating signaling molecules in yeast and mammalian cells; however, the manner in which they might be involved in male-female interactions in plants is unknown. In this study, we identified Arabidopsis thaliana vacuolar protein sorting 41 (AtVPS41), encoded by a single-copy gene with sequence similarity to yeast Vps41p, as a new factor controlling pollen tube-stigma interaction. Loss of AtVPS41 function disrupted penetration of pollen tubes into the transmitting tissue and thus led to failed male transmission. In the pollen tubes, AtVPS41 protein is associated with PVCs and the tonoplast. We demonstrate that AtVPS41 is required for the late stage of the endocytic pathway (i.e., endomembrane trafficking from PVCs to vacuoles) because internalization of cell-surface molecules was normal in the vps41 deficient pollen tubes, whereas PVC-to-vacuole trafficking was impaired. We further show that the CHCR domain is required for subcellular localization and biological functioning of AtVPS41. These results indicate that the AtVPS41 mediated late stage of the endocytic pathway is essential for pollen tube-stigma interaction in Arabidopsis. PMID- 27185922 TI - Evaluating the privacy properties of telephone metadata. AB - Since 2013, a stream of disclosures has prompted reconsideration of surveillance law and policy. One of the most controversial principles, both in the United States and abroad, is that communications metadata receives substantially less protection than communications content. Several nations currently collect telephone metadata in bulk, including on their own citizens. In this paper, we attempt to shed light on the privacy properties of telephone metadata. Using a crowdsourcing methodology, we demonstrate that telephone metadata is densely interconnected, can trivially be reidentified, and can be used to draw sensitive inferences. PMID- 27185921 TI - Biodiversity enhances reef fish biomass and resistance to climate change. AB - Fishes are the most diverse group of vertebrates, play key functional roles in aquatic ecosystems, and provide protein for a billion people, especially in the developing world. Those functions are compromised by mounting pressures on marine biodiversity and ecosystems. Because of its economic and food value, fish biomass production provides an unusually direct link from biodiversity to critical ecosystem services. We used the Reef Life Survey's global database of 4,556 standardized fish surveys to test the importance of biodiversity to fish production relative to 25 environmental drivers. Temperature, biodiversity, and human influence together explained 47% of the global variation in reef fish biomass among sites. Fish species richness and functional diversity were among the strongest predictors of fish biomass, particularly for the large-bodied species and carnivores preferred by fishers, and these biodiversity effects were robust to potentially confounding influences of sample abundance, scale, and environmental correlations. Warmer temperatures increased biomass directly, presumably by raising metabolism, and indirectly by increasing diversity, whereas temperature variability reduced biomass. Importantly, diversity and climate interact, with biomass of diverse communities less affected by rising and variable temperatures than species-poor communities. Biodiversity thus buffers global fish biomass from climate change, and conservation of marine biodiversity can stabilize fish production in a changing ocean. PMID- 27185923 TI - A lead isotope perspective on urban development in ancient Naples. AB - The influence of a sophisticated water distribution system on urban development in Roman times is tested against the impact of Vesuvius volcanic activity, in particular the great eruption of AD 79, on all of the ancient cities of the Bay of Naples (Neapolis). Written accounts on urbanization outside of Rome are scarce and the archaeological record sketchy, especially during the tumultuous fifth and sixth centuries AD when Neapolis became the dominant city in the region. Here we show that isotopic ratios of lead measured on a well-dated sedimentary sequence from Neapolis' harbor covering the first six centuries CE have recorded how the AD 79 eruption was followed by a complete overhaul of Neapolis' water supply network. The Pb isotopic signatures of the sediments further reveal that the previously steady growth of Neapolis' water distribution system ceased during the collapse of the fifth century AD, although vital repairs to this critical infrastructure were still carried out in the aftermath of invasions and volcanic eruptions. PMID- 27185925 TI - Clouds at Barbados are representative of clouds across the trade wind regions in observations and climate models. AB - Trade wind regions cover most of the tropical oceans, and the prevailing cloud type is shallow cumulus. These small clouds are parameterized by climate models, and changes in their radiative effects strongly and directly contribute to the spread in estimates of climate sensitivity. This study investigates the structure and variability of these clouds in observations and climate models. The study builds upon recent detailed model evaluations using observations from the island of Barbados. Using a dynamical regimes framework, satellite and reanalysis products are used to compare the Barbados region and the broader tropics. It is shown that clouds in the Barbados region are similar to those across the trade wind regions, implying that observational findings from the Barbados Cloud Observatory are relevant to clouds across the tropics. The same methods are applied to climate models to evaluate the simulated clouds. The models generally capture the cloud radiative effect, but underestimate cloud cover and show an array of cloud vertical structures. Some models show strong biases in the environment of the Barbados region in summer, weakening the connection between the regional biases and those across the tropics. Even bearing that limitation in mind, it is shown that covariations of cloud and environmental properties in the models are inconsistent with observations. The models tend to misrepresent sensitivity to moisture variations and inversion characteristics. These model errors are likely connected to cloud feedback in climate projections, and highlight the importance of the representation of shallow cumulus convection. PMID- 27185927 TI - Correction for Buhrman et al., Quantum communication complexity advantage implies violation of a Bell inequality. PMID- 27185924 TI - Striatal cholinergic interneurons generate beta and gamma oscillations in the corticostriatal circuit and produce motor deficits. AB - Cortico-basal ganglia-thalamic (CBT) neural circuits are critical modulators of cognitive and motor function. When compromised, these circuits contribute to neurological and psychiatric disorders, such as Parkinson's disease (PD). In PD, motor deficits correlate with the emergence of exaggerated beta frequency (15-30 Hz) oscillations throughout the CBT network. However, little is known about how specific cell types within individual CBT brain regions support the generation, propagation, and interaction of oscillatory dynamics throughout the CBT circuit or how specific oscillatory dynamics are related to motor function. Here, we investigated the role of striatal cholinergic interneurons (SChIs) in generating beta and gamma oscillations in cortical-striatal circuits and in influencing movement behavior. We found that selective stimulation of SChIs via optogenetics in normal mice robustly and reversibly amplified beta and gamma oscillations that are supported by distinct mechanisms within striatal-cortical circuits. Whereas beta oscillations are supported robustly in the striatum and all layers of primary motor cortex (M1) through a muscarinic-receptor mediated mechanism, gamma oscillations are largely restricted to the striatum and the deeper layers of M1. Finally, SChI activation led to parkinsonian-like motor deficits in otherwise normal mice. These results highlight the important role of striatal cholinergic interneurons in supporting oscillations in the CBT network that are closely related to movement and parkinsonian motor symptoms. PMID- 27185926 TI - BPTF transduces MITF-driven prosurvival signals in melanoma cells. AB - Microphthalmia-associated transcription factor (MITF) plays a critical and complex role in melanocyte transformation. Although several downstream targets of MITF action have been identified, the precise mechanisms by which MITF promotes melanocytic tumor progression are incompletely understood. Recent studies identified an oncogenic role for the bromodomain plant homeodomain finger transcription factor (BPTF) gene in melanoma progression, in part through activation of BCL2, a canonical target of MITF signaling. Analysis of the BPTF promoter identified a putative MITF-binding site, suggesting that MITF may regulate BPTF expression. Overexpression of MITF resulted in up-regulation of BPTF in a panel of melanoma and melanocyte cell lines. shRNA-mediated down regulation of MITF in melanoma cells was accompanied by down-regulation of BPTF and BPTF-regulated genes (including BCL2) and resulted in reduced proliferative capacity of melanoma cells. The suppression of cell growth mediated by MITF silencing was rescued by overexpression of BPTF cDNA. Binding of MITF to the BPTF promoter was demonstrated using ChIP analysis. MITF overexpression resulted in direct transcriptional activation of BPTF, as evidenced by increased luciferase activity driven by the BPTF promoter. These results indicate that BPTF transduces key prosurvival signals driven by MITF, further supporting its important role in promoting melanoma cell survival and progression. PMID- 27185928 TI - Isoprene photochemistry over the Amazon rainforest. AB - Isoprene photooxidation is a major driver of atmospheric chemistry over forested regions. Isoprene reacts with hydroxyl radicals (OH) and molecular oxygen to produce isoprene peroxy radicals (ISOPOO). These radicals can react with hydroperoxyl radicals (HO2) to dominantly produce hydroxyhydroperoxides (ISOPOOH). They can also react with nitric oxide (NO) to largely produce methyl vinyl ketone (MVK) and methacrolein (MACR). Unimolecular isomerization and bimolecular reactions with organic peroxy radicals are also possible. There is uncertainty about the relative importance of each of these pathways in the atmosphere and possible changes because of anthropogenic pollution. Herein, measurements of ISOPOOH and MVK + MACR concentrations are reported over the central region of the Amazon basin during the wet season. The research site, downwind of an urban region, intercepted both background and polluted air masses during the GoAmazon2014/5 Experiment. Under background conditions, the confidence interval for the ratio of the ISOPOOH concentration to that of MVK + MACR spanned 0.4-0.6. This result implies a ratio of the reaction rate of ISOPOO with HO2 to that with NO of approximately unity. A value of unity is significantly smaller than simulated at present by global chemical transport models for this important, nominally low-NO, forested region of Earth. Under polluted conditions, when the concentrations of reactive nitrogen compounds were high (>1 ppb), ISOPOOH concentrations dropped below the instrumental detection limit (<60 ppt). This abrupt shift in isoprene photooxidation, sparked by human activities, speaks to ongoing and possible future changes in the photochemistry active over the Amazon rainforest. PMID- 27185929 TI - Structure of faustovirus, a large dsDNA virus. AB - Many viruses protect their genome with a combination of a protein shell with or without a membrane layer. Here we describe the structure of faustovirus, the first DNA virus (to our knowledge) that has been found to use two protein shells to encapsidate and protect its genome. The crystal structure of the major capsid protein, in combination with cryo-electron microscopy structures of two different maturation stages of the virus, shows that the outer virus shell is composed of a double jelly-roll protein that can be found in many double-stranded DNA viruses. The structure of the repeating hexameric unit of the inner shell is different from all other known capsid proteins. In addition to the unique architecture, the region of the genome that encodes the major capsid protein stretches over 17,000 bp and contains a large number of introns and exons. This complexity might help the virus to rapidly adapt to new environments or hosts. PMID- 27185930 TI - In-drop capillary spooling of spider capture thread inspires hybrid fibers with mixed solid-liquid mechanical properties. AB - An essential element in the web-trap architecture, the capture silk spun by ecribellate orb spiders consists of glue droplets sitting astride a silk filament. Mechanically this thread presents a mixed solid-liquid behavior unknown to date. Under extension, capture silk behaves as a particularly stretchy solid, owing to its molecular nanosprings, but it totally switches behavior in compression to now become liquid-like: It shrinks with no apparent limit while exerting a constant tension. Here, we unravel the physics underpinning the unique behavior of this "liquid wire" and demonstrate that its mechanical response originates in the shape-switching of the silk filament induced by buckling within the droplets. Learning from this natural example of geometry and mechanics, we manufactured programmable liquid wires that present previously unidentified pathways for the design of new hybrid solid-liquid materials. PMID- 27185932 TI - Laser-assisted direct ink writing of planar and 3D metal architectures. AB - The ability to pattern planar and freestanding 3D metallic architectures at the microscale would enable myriad applications, including flexible electronics, displays, sensors, and electrically small antennas. A 3D printing method is introduced that combines direct ink writing with a focused laser that locally anneals printed metallic features "on-the-fly." To optimize the nozzle-to-laser separation distance, the heat transfer along the printed silver wire is modeled as a function of printing speed, laser intensity, and pulse duration. Laser assisted direct ink writing is used to pattern highly conductive, ductile metallic interconnects, springs, and freestanding spiral architectures on flexible and rigid substrates. PMID- 27185933 TI - Ocean dynamics, not dust, have controlled equatorial Pacific productivity over the past 500,000 years. AB - Biological productivity in the equatorial Pacific is relatively high compared with other low-latitude regimes, especially east of the dateline, where divergence driven by the trade winds brings nutrient-rich waters of the Equatorial Undercurrent to the surface. The equatorial Pacific is one of the three principal high-nutrient low-chlorophyll ocean regimes where biological utilization of nitrate and phosphate is limited, in part, by the availability of iron. Throughout most of the equatorial Pacific, upwelling of water from the Equatorial Undercurrent supplies far more dissolved iron than is delivered by dust, by as much as two orders of magnitude. Nevertheless, recent studies have inferred that the greater supply of dust during ice ages stimulated greater utilization of nutrients within the region of upwelling on the equator, thereby contributing to the sequestration of carbon in the ocean interior. Here we present proxy records for dust and for biological productivity over the past 500 ky at three sites spanning the breadth of the equatorial Pacific Ocean to test the dust fertilization hypothesis. Dust supply peaked under glacial conditions, consistent with previous studies, whereas proxies of export production exhibit maxima during ice age terminations. Temporal decoupling between dust supply and biological productivity indicates that other factors, likely involving ocean dynamics, played a greater role than dust in regulating equatorial Pacific productivity. PMID- 27185931 TI - Severe adult malaria is associated with specific PfEMP1 adhesion types and high parasite biomass. AB - The interplay between cellular and molecular determinants that lead to severe malaria in adults is unexplored. Here, we analyzed parasite virulence factors in an infected adult population in India and investigated whether severe malaria isolates impair endothelial protein C receptor (EPCR), a protein involved in coagulation and endothelial barrier permeability. Severe malaria isolates overexpressed specific members of the Plasmodium falciparum var gene/PfEMP1 (P. falciparum erythrocyte membrane protein 1) family that bind EPCR, including DC8 var genes that have previously been linked to severe pediatric malaria. Machine learning analysis revealed that DC6- and DC8-encoding var transcripts in combination with high parasite biomass were the strongest indicators of patient hospitalization and disease severity. We found that DC8 CIDRalpha1 domains from severe malaria isolates had substantial differences in EPCR binding affinity and blockade activity for its ligand activated protein C. Additionally, even a low level of inhibition exhibited by domains from two cerebral malaria isolates was sufficient to interfere with activated protein C-barrier protective activities in human brain endothelial cells. Our findings demonstrate an interplay between parasite biomass and specific PfEMP1 adhesion types in the development of adult severe malaria, and indicate that low impairment of EPCR function may contribute to parasite virulence. PMID- 27185934 TI - Elevated CO2 maintains grassland net carbon uptake under a future heat and drought extreme. AB - Extreme climatic events (ECEs) such as droughts and heat waves are predicted to increase in intensity and frequency and impact the terrestrial carbon balance. However, we lack direct experimental evidence of how the net carbon uptake of ecosystems is affected by ECEs under future elevated atmospheric CO2 concentrations (eCO2). Taking advantage of an advanced controlled environment facility for ecosystem research (Ecotron), we simulated eCO2 and extreme cooccurring heat and drought events as projected for the 2050s and analyzed their effects on the ecosystem-level carbon and water fluxes in a C3 grassland. Our results indicate that eCO2 not only slows down the decline of ecosystem carbon uptake during the ECE but also enhances its recovery after the ECE, as mediated by increases of root growth and plant nitrogen uptake induced by the ECE. These findings indicate that, in the predicted near future climate, eCO2 could mitigate the effects of extreme droughts and heat waves on ecosystem net carbon uptake. PMID- 27185935 TI - A binding site outside the canonical PDZ domain determines the specific interaction between Shank and SAPAP and their function. AB - Shank and SAPAP (synapse-associated protein 90/postsynaptic density-95-associated protein) are two highly abundant scaffold proteins that directly interact with each other to regulate excitatory synapse development and plasticity. Mutations of SAPAP, but not other reported Shank PDZ domain binders, share a significant overlap on behavioral abnormalities with the mutations of Shank both in patients and in animal models. The molecular mechanism governing the exquisite specificity of the Shank/SAPAP interaction is not clear, however. Here we report that a sequence preceding the canonical PDZ domain of Shank, together with the elongated PDZ BC loop, form another binding site for a sequence upstream of the SAPAP PDZ binding motif, leading to a several hundred-fold increase in the affinity of the Shank/SAPAP interaction. We provide evidence that the specific interaction afforded by this newly identified site is required for Shank synaptic targeting and the Shank-induced synaptic activity increase. Our study provides a molecular explanation of how Shank and SAPAP dosage changes due to their gene copy number variations can contribute to different psychiatric disorders. PMID- 27185936 TI - Cryo-EM reveals the steric zipper structure of a light chain-derived amyloid fibril. AB - Amyloid fibrils are proteinaceous aggregates associated with diseases in humans and animals. The fibrils are defined by intermolecular interactions between the fibril-forming polypeptide chains, but it has so far remained difficult to reveal the assembly of the peptide subunits in a full-scale fibril. Using electron cryomicroscopy (cryo-EM), we present a reconstruction of a fibril formed from the pathogenic core of an amyloidogenic immunoglobulin (Ig) light chain. The fibril density shows a lattice-like assembly of face-to-face packed peptide dimers that corresponds to the structure of steric zippers in peptide crystals. Interpretation of the density map with a molecular model enabled us to identify the intermolecular interactions between the peptides and rationalize the hierarchical structure of the fibril based on simple chemical principles. PMID- 27185937 TI - Pravastatin ameliorates placental vascular defects, fetal growth, and cardiac function in a model of glucocorticoid excess. AB - Fetoplacental glucocorticoid overexposure is a significant mechanism underlying fetal growth restriction and the programming of adverse health outcomes in the adult. Placental glucocorticoid inactivation by 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) plays a key role. We previously discovered that Hsd11b2(-/-) mice, lacking 11beta-HSD2, show marked underdevelopment of the placental vasculature. We now explore the consequences for fetal cardiovascular development and whether this is reversible. We studied Hsd11b2(+/+), Hsd11b2(+/ ), and Hsd11b2(-/-) littermates from heterozygous (Hsd11b(+/-)) matings at embryonic day (E)14.5 and E17.5, where all three genotypes were present to control for maternal effects. Using high-resolution ultrasound, we found that umbilical vein blood velocity in Hsd11b2(-/-) fetuses did not undergo the normal gestational increase seen in Hsd11b2(+/+) littermates. Similarly, the resistance index in the umbilical artery did not show the normal gestational decline. Surprisingly, given that 11beta-HSD2 absence is predicted to initiate early maturation, the E/A wave ratio was reduced at E17.5 in Hsd11b2(-/-) fetuses, suggesting impaired cardiac function. Pravastatin administration from E6.5, which increases placental vascular endothelial growth factor A and, thus, vascularization, increased placental fetal capillary volume, ameliorated the aberrant umbilical cord velocity, normalized fetal weight, and improved the cardiac function of Hsd11b2(-/-) fetuses. This improved cardiac function occurred despite persisting indications of increased glucocorticoid exposure in the Hsd11b2(-/-) fetal heart. Thus, the pravastatin-induced enhancement of fetal capillaries within the placenta and the resultant hemodynamic changes correspond with restored fetal cardiac function. Statins may represent a useful therapeutic approach to intrauterine growth retardation due to placental vascular hypofunction. PMID- 27185938 TI - Leukotriene E4 elicits respiratory epithelial cell mucin release through the G protein-coupled receptor, GPR99. AB - Cysteinyl leukotrienes (cysLTs), leukotriene C4 (LTC4), LTD4, and LTE4 are proinflammatory lipid mediators with pathobiologic function in asthma. LTE4, the stable cysLT, is a weak agonist for the type 1 and type 2 cysLT receptors (CysLTRs), which constrict airway smooth muscle, but elicits airflow obstruction and pulmonary inflammation in patients with asthma. We recently identified GPR99 as a high-affinity receptor for LTE4 that mediates cutaneous vascular permeability. Here we demonstrate that a single intranasal exposure to extract from the respiratory pathogen Alternaria alternata elicits profound epithelial cell (EpC) mucin release and submucosal swelling in the nasal mucosa of mice that depends on cysLTs, as it is absent in mice deficient in the terminal enzyme for cysLT biosynthesis, LTC4 synthase (LTC4S). These mucosal changes are associated with mast cell (MC) activation and absent in MC-deficient mice, suggesting a role for MCs in control of EpC function. Of the three CysLTRs, only GPR99-deficient mice are fully protected from EpC mucin release and swelling elicited by Alternaria or by intranasal LTE4 GPR99 expression is detected on lung and nasal EpCs, which release mucin to doses of LTE4 one log lower than that required to elicit submucosal swelling. Finally, mice deficient in MCs, LTC4S, or GPR99 have reduced baseline numbers of goblet cells, indicating an additional function in regulating EpC homeostasis. These results demonstrate a novel role for GPR99 among CysLTRs in control of respiratory EpC function and suggest that inhibition of LTE4 and of GPR99 may have therapeutic benefits in asthma. PMID- 27185939 TI - Target shape dependence in a simple model of receptor-mediated endocytosis and phagocytosis. AB - Phagocytosis and receptor-mediated endocytosis are vitally important particle uptake mechanisms in many cell types, ranging from single-cell organisms to immune cells. In both processes, engulfment by the cell depends critically on both particle shape and orientation. However, most previous theoretical work has focused only on spherical particles and hence disregards the wide-ranging particle shapes occurring in nature, such as those of bacteria. Here, by implementing a simple model in one and two dimensions, we compare and contrast receptor-mediated endocytosis and phagocytosis for a range of biologically relevant shapes, including spheres, ellipsoids, capped cylinders, and hourglasses. We find a whole range of different engulfment behaviors with some ellipsoids engulfing faster than spheres, and that phagocytosis is able to engulf a greater range of target shapes than other types of endocytosis. Further, the 2D model can explain why some nonspherical particles engulf fastest (not at all) when presented to the membrane tip-first (lying flat). Our work reveals how some bacteria may avoid being internalized simply because of their shape, and suggests shapes for optimal drug delivery. PMID- 27185942 TI - Correction for Bryant et al., Detecting affiliation in colaughter across 24 societies. PMID- 27185940 TI - S-adenosyl methionine is necessary for inhibition of the methyltransferase G9a by the lysine 9 to methionine mutation on histone H3. AB - Lysine to methionine (K-to-M) mutations in genes encoding histone H3 are thought to drive a subset of pediatric brain and bone cancers. These high-frequency K-to M mutations occur at sites of methylation on histone H3, and tumors containing the mutant histones exhibit a global loss of specific histone methylation marks. Previous studies showed that K-to-M mutant histones, also known as oncohistones, are potent orthosteric inhibitors of specific Su(var)3-9, Enhancer-of-zeste, Trithorax (SET) domain methyltransferases. However, the biochemical and biophysical details of the interaction between K-to-M mutant histones and the respective SET domain methyltransferases are currently unknown. Here, we use the histone H3K9-directed methyltransferase G9a as a model to explore the mechanism of inhibition by K-to-M oncohistones. X-ray cocrystal structures revealed that the K9M residue of histone H3 occupies the active site cavity of G9a, and kinetic analysis indicates competitive inhibition of G9a by histone H3K9M. Additionally, we find that the cofactor S-adenosyl methionine (SAM) is necessary for stable interaction between G9a and H3K9M histone. Consistent with the formation of a ternary complex, we find that the inhibitory peptide is uncompetitive with regard to SAM. These data and others indicate that K-to-M oncohistones promote global loss of specific lysine methylation through sequestration and inhibition of SAM bound SET domain methyltransferases. PMID- 27185941 TI - Memories of unethical actions become obfuscated over time. AB - Despite our optimistic belief that we would behave honestly when facing the temptation to act unethically, we often cross ethical boundaries. This paper explores one possibility of why people engage in unethical behavior over time by suggesting that their memory for their past unethical actions is impaired. We propose that, after engaging in unethical behavior, individuals' memories of their actions become more obfuscated over time because of the psychological distress and discomfort such misdeeds cause. In nine studies (n = 2,109), we show that engaging in unethical behavior produces changes in memory so that memories of unethical actions gradually become less clear and vivid than memories of ethical actions or other types of actions that are either positive or negative in valence. We term this memory obfuscation of one's unethical acts over time "unethical amnesia." Because of unethical amnesia, people are more likely to act dishonestly repeatedly over time. PMID- 27185943 TI - The need to respect nature and its limits challenges society and conservation science. AB - Increasing human population interacts with local and global environments to deplete biodiversity and resources humans depend on, thus challenging societal values centered on growth and relying on technology to mitigate environmental stress. Although the need to address the environmental crisis, central to conservation science, generated greener versions of the growth paradigm, we need fundamental shifts in values that ensure transition from a growth-centered society to one acknowledging biophysical limits and centered on human well-being and biodiversity conservation. We discuss the role conservation science can play in this transformation, which poses ethical challenges and obstacles. We analyze how conservation and economics can achieve better consonance, the extent to which technology should be part of the solution, and difficulties the "new conservation science" has generated. An expanded ambition for conservation science should reconcile day-to-day action within the current context with uncompromising, explicit advocacy for radical transitions in core attitudes and processes that govern our interactions with the biosphere. A widening of its focus to understand better the interconnectedness between human well-being and acknowledgment of the limits of an ecologically functional and diverse planet will need to integrate ecological and social sciences better. Although ecology can highlight limits to growth and consequences of ignoring them, social sciences are necessary to diagnose societal mechanisms at work, how to correct them, and potential drivers of social change. PMID- 27185945 TI - Open chromatin reveals the functional maize genome. AB - Cellular processes mediated through nuclear DNA must contend with chromatin. Chromatin structural assays can efficiently integrate information across diverse regulatory elements, revealing the functional noncoding genome. In this study, we use a differential nuclease sensitivity assay based on micrococcal nuclease (MNase) digestion to discover open chromatin regions in the maize genome. We find that maize MNase-hypersensitive (MNase HS) regions localize around active genes and within recombination hotspots, focusing biased gene conversion at their flanks. Although MNase HS regions map to less than 1% of the genome, they consistently explain a remarkably large amount (~40%) of heritable phenotypic variance in diverse complex traits. MNase HS regions are therefore on par with coding sequences as annotations that demarcate the functional parts of the maize genome. These results imply that less than 3% of the maize genome (coding and MNase HS regions) may give rise to the overwhelming majority of phenotypic variation, greatly narrowing the scope of the functional genome. PMID- 27185944 TI - Transient neuronal coactivations embedded in globally propagating waves underlie resting-state functional connectivity. AB - Resting-state functional connectivity (FC), which measures the correlation of spontaneous hemodynamic signals (HemoS) between brain areas, is widely used to study brain networks noninvasively. It is commonly assumed that spatial patterns of HemoS-based FC (Hemo-FC) reflect large-scale dynamics of underlying neuronal activity. To date, studies of spontaneous neuronal activity cataloged heterogeneous types of events ranging from waves of activity spanning the entire neocortex to flash-like activations of a set of anatomically connected cortical areas. However, it remains unclear how these various types of large-scale dynamics are interrelated. More importantly, whether each type of large-scale dynamics contributes to Hemo-FC has not been explored. Here, we addressed these questions by simultaneously monitoring neuronal calcium signals (CaS) and HemoS in the entire neocortex of mice at high spatiotemporal resolution. We found a significant relationship between two seemingly different types of large-scale spontaneous neuronal activity-namely, global waves propagating across the neocortex and transient coactivations among cortical areas sharing high FC. Different sets of cortical areas, sharing high FC within each set, were coactivated at different timings of the propagating global waves, suggesting that spatial information of cortical network characterized by FC was embedded in the phase of the global waves. Furthermore, we confirmed that such transient coactivations in CaS were indeed converted into spatially similar coactivations in HemoS and were necessary to sustain the spatial structure of Hemo-FC. These results explain how global waves of spontaneous neuronal activity propagating across large-scale cortical network contribute to Hemo-FC in the resting state. PMID- 27185947 TI - Transactional information is remarkably revelatory. PMID- 27185946 TI - Phasic dopamine release in the medial prefrontal cortex enhances stimulus discrimination. AB - Phasic dopamine (DA) release is believed to guide associative learning. Most studies have focused on projections from the ventral tegmental area (VTA) to the striatum, and the action of DA in other VTA target regions remains unclear. Using optogenetic activation of VTA projections, we examined DA function in the medial prefrontal cortex (mPFC). We found that mice perceived optogenetically induced DA release in mPFC as neither rewarding nor aversive, and did not change their previously learned behavior in response to DA transients. However, repetitive temporal pairing of an auditory conditioned stimulus (CS) with mPFC DA release resulted in faster learning of a subsequent task involving discrimination of the same CS against unpaired stimuli. Similar results were obtained using both appetitive and aversive unconditioned stimuli, supporting the notion that DA transients in mPFC do not represent valence. Using extracellular recordings, we found that CS-DA pairings increased firing of mPFC neurons in response to CSs, and administration of D1 or D2 DA-receptor antagonists in mPFC during learning impaired stimulus discrimination. We conclude that DA transients tune mPFC neurons for the recognition of behaviorally relevant events during learning. PMID- 27185948 TI - Tissue-specific dynamin-1 deletion at the calyx of Held decreases short-term depression through a mechanism distinct from vesicle resupply. AB - Dynamin is a large GTPase with a crucial role in synaptic vesicle regeneration. Acute dynamin inhibition impairs neurotransmitter release, in agreement with the protein's established role in vesicle resupply. Here, using tissue-specific dynamin-1 knockout [conditional knockout (cKO)] mice at a fast central synapse that releases neurotransmitter at high rates, we report that dynamin-1 deletion unexpectedly leads to enhanced steady-state neurotransmission and consequently less synaptic depression during brief periods of high-frequency stimulation. These changes are also accompanied by increased transmission failures. Interestingly, synaptic vesicle resupply and several other synaptic properties remain intact, including basal neurotransmission, presynaptic Ca(2+) influx, initial release probability, and postsynaptic receptor saturation and desensitization. However, acute application of Latrunculin B, a reagent known to induce actin depolymerization and impair bulk and ultrafast endocytosis, has a stronger effect on steady-state depression in cKO than in control and brings the depression down to a control level. The slow phase of presynaptic capacitance decay following strong stimulation is impaired in cKO; the rapid capacitance changes immediately after strong depolarization are also different between control and cKO and sensitive to Latrunculin B. These data raise the possibility that, in addition to its established function in regenerating synaptic vesicles, the endocytosis protein dynamin-1 may have an impact on short-term synaptic depression. This role comes into play primarily during brief high-frequency stimulation. PMID- 27185950 TI - Time discounting and criminal behavior. AB - One of the most basic predictions of almost any model of crime is that individual time preferences matter. However, empirical evidence on this fundamental property is essentially nonexistent. To our knowledge, this paper provides the first pieces of evidence on the link between time discounting and crime. We use a unique dataset that combines a survey-based measure of time discount rates (at age 13) with detailed longitudinal register data on criminal behavior spanning over 18 y. Our results show that individuals with short time horizons have a significantly higher risk of criminal involvement later in life. The magnitude of the relationship is substantial and corresponds to roughly one-third of the association between intelligence and crime. PMID- 27185952 TI - Role of updraft velocity in temporal variability of global cloud hydrometeor number. AB - Understanding how dynamical and aerosol inputs affect the temporal variability of hydrometeor formation in climate models will help to explain sources of model diversity in cloud forcing, to provide robust comparisons with data, and, ultimately, to reduce the uncertainty in estimates of the aerosol indirect effect. This variability attribution can be done at various spatial and temporal resolutions with metrics derived from online adjoint sensitivities of droplet and crystal number to relevant inputs. Such metrics are defined and calculated from simulations using the NASA Goddard Earth Observing System Model, Version 5 (GEOS 5) and the National Center for Atmospheric Research Community Atmosphere Model Version 5.1 (CAM5.1). Input updraft velocity fluctuations can explain as much as 48% of temporal variability in output ice crystal number and 61% in droplet number in GEOS-5 and up to 89% of temporal variability in output ice crystal number in CAM5.1. In both models, this vertical velocity attribution depends strongly on altitude. Despite its importance for hydrometeor formation, simulated vertical velocity distributions are rarely evaluated against observations due to the sparsity of relevant data. Coordinated effort by the atmospheric community to develop more consistent, observationally based updraft treatments will help to close this knowledge gap. PMID- 27185949 TI - Natural mutations in a Staphylococcus aureus virulence regulator attenuate cytotoxicity but permit bacteremia and abscess formation. AB - Staphylococcus aureus is a major bacterial pathogen, which causes severe blood and tissue infections that frequently emerge by autoinfection with asymptomatically carried nose and skin populations. However, recent studies report that bloodstream isolates differ systematically from those found in the nose and skin, exhibiting reduced toxicity toward leukocytes. In two patients, an attenuated toxicity bloodstream infection evolved from an asymptomatically carried high-toxicity nasal strain by loss-of-function mutations in the gene encoding the transcription factor repressor of surface proteins (rsp). Here, we report that rsp knockout mutants lead to global transcriptional and proteomic reprofiling, and they exhibit the greatest signal in a genome-wide screen for genes influencing S. aureus survival in human cells. This effect is likely to be mediated in part via SSR42, a long-noncoding RNA. We show that rsp controls SSR42 expression, is induced by hydrogen peroxide, and is required for normal cytotoxicity and hemolytic activity. Rsp inactivation in laboratory- and bacteremia-derived mutants attenuates toxin production, but up-regulates other immune subversion proteins and reduces lethality during experimental infection. Crucially, inactivation of rsp preserves bacterial dissemination, because it affects neither formation of deep abscesses in mice nor survival in human blood. Thus, we have identified a spontaneously evolving, attenuated-cytotoxicity, nonhemolytic S. aureus phenotype, controlled by a pleiotropic transcriptional regulator/noncoding RNA virulence regulatory system, capable of causing S. aureus bloodstream infections. Such a phenotype could promote deep infection with limited early clinical manifestations, raising concerns that bacterial evolution within the human body may contribute to severe infection. PMID- 27185953 TI - Structural characterization of the ternary complex that mediates termination of NF-kappaB signaling by IkappaBalpha. AB - The transcription factor NF-kappaB is used in many systems for the transduction of extracellular signals into the expression of signal-responsive genes. Published structural data explain the activation of NF-kappaB through degradation of its dedicated inhibitor IkappaBalpha, but the mechanism by which NF-kappaB mediated signaling is turned off by its removal from the DNA in the presence of newly synthesized IkappaBalpha (termed stripping) is unknown. Previous kinetic studies showed that IkappaBalpha accelerates NF-kappaB dissociation from DNA, and a transient ternary complex between NF-kappaB, its cognate DNA sequence, and IkappaBalpha was observed. Here we structurally characterize the >100-kDa ternary complex by NMR and negative stain EM and show a modeled structure that is consistent with the measurements. These data provide a structural basis for previously unidentified insights into the molecular mechanism of stripping. PMID- 27185951 TI - Chemo-mechanical pushing of proteins along single-stranded DNA. AB - Single-stranded (ss)DNA binding (SSB) proteins bind with high affinity to ssDNA generated during DNA replication, recombination, and repair; however, these SSBs must eventually be displaced from or reorganized along the ssDNA. One potential mechanism for reorganization is for an ssDNA translocase (ATP-dependent motor) to push the SSB along ssDNA. Here we use single molecule total internal reflection fluorescence microscopy to detect such pushing events. When Cy5-labeled Escherichia coli (Ec) SSB is bound to surface-immobilized 3'-Cy3-labeled ssDNA, a fluctuating FRET signal is observed, consistent with random diffusion of SSB along the ssDNA. Addition of Saccharomyces cerevisiae Pif1, a 5' to 3' ssDNA translocase, results in the appearance of isolated, irregularly spaced saw-tooth FRET spikes only in the presence of ATP. These FRET spikes result from translocase-induced directional (5' to 3') pushing of the SSB toward the 3' ssDNA end, followed by displacement of the SSB from the DNA end. Similar ATP-dependent pushing events, but in the opposite (3' to 5') direction, are observed with EcRep and EcUvrD (both 3' to 5' ssDNA translocases). Simulations indicate that these events reflect active pushing by the translocase. The ability of translocases to chemo-mechanically push heterologous SSB proteins along ssDNA provides a potential mechanism for reorganization and clearance of tightly bound SSBs from ssDNA. PMID- 27185955 TI - Prevalent vegetation growth enhancement in urban environment. AB - Urbanization, a dominant global demographic trend, leads to various changes in environments (e.g., atmospheric CO2 increase, urban heat island). Cities experience global change decades ahead of other systems so that they are natural laboratories for studying responses of other nonurban biological ecosystems to future global change. However, the impacts of urbanization on vegetation growth are not well understood. Here, we developed a general conceptual framework for quantifying the impacts of urbanization on vegetation growth and applied it in 32 Chinese cities. Results indicated that vegetation growth, as surrogated by satellite-observed vegetation index, decreased along urban intensity across all cities. At the same time, vegetation growth was enhanced at 85% of the places along the intensity gradient, and the relative enhancement increased with urban intensity. This growth enhancement offset about 40% of direct loss of vegetation productivity caused by replacing productive vegetated surfaces with nonproductive impervious surfaces. In light of current and previous field studies, we conclude that vegetation growth enhancement is prevalent in urban settings. Urban environments do provide ideal natural laboratories to observe biological responses to environmental changes that are difficult to mimic in manipulative experiments. However, one should be careful in extrapolating the finding to nonurban environments because urban vegetation is usually intensively managed, and attribution of the responses to diverse driving forces will be challenging but must be pursued. PMID- 27185956 TI - KdgF, the missing link in the microbial metabolism of uronate sugars from pectin and alginate. AB - Uronates are charged sugars that form the basis of two abundant sources of biomass-pectin and alginate-found in the cell walls of terrestrial plants and marine algae, respectively. These polysaccharides represent an important source of carbon to those organisms with the machinery to degrade them. The microbial pathways of pectin and alginate metabolism are well studied and essentially parallel; in both cases, unsaturated monouronates are produced and processed into the key metabolite 2-keto-3-deoxygluconate (KDG). The enzymes required to catalyze each step have been identified within pectinolytic and alginolytic microbes; yet the function of a small ORF, kdgF, which cooccurs with the genes for these enzymes, is unknown. Here we show that KdgF catalyzes the conversion of pectin- and alginate-derived 4,5-unsaturated monouronates to linear ketonized forms, a step in uronate metabolism that was previously thought to occur spontaneously. Using enzyme assays, NMR, mutagenesis, and deletion of kdgF, we show that KdgF proteins from both pectinolytic and alginolytic bacteria catalyze the ketonization of unsaturated monouronates and contribute to efficient production of KDG. We also report the X-ray crystal structures of two KdgF proteins and propose a mechanism for catalysis. The discovery of the function of KdgF fills a 50-y-old gap in the knowledge of uronate metabolism. Our findings have implications not only for the understanding of an important metabolic pathway, but also the role of pectinolysis in plant-pathogen virulence and the growing interest in the use of pectin and alginate as feedstocks for biofuel production. PMID- 27185954 TI - Variants within the SP110 nuclear body protein modify risk of canine degenerative myelopathy. AB - Canine degenerative myelopathy (DM) is a naturally occurring neurodegenerative disease with similarities to some forms of amyotrophic lateral sclerosis (ALS). Most dogs that develop DM are homozygous for a common superoxide dismutase 1 gene (SOD1) mutation. However, not all dogs homozygous for this mutation develop disease. We performed a genome-wide association analysis in the Pembroke Welsh Corgi (PWC) breed comparing DM-affected and -unaffected dogs homozygous for the SOD1 mutation. The analysis revealed a modifier locus on canine chromosome 25. A haplotype within the SP110 nuclear body protein (SP110) was present in 40% of affected compared with 4% of unaffected dogs (P = 1.5 * 10(-5)), and was associated with increased probability of developing DM (P = 4.8 * 10(-6)) and earlier onset of disease (P = 1.7 * 10(-5)). SP110 is a nuclear body protein involved in the regulation of gene transcription. Our findings suggest that variations in SP110-mediated gene transcription may underlie, at least in part, the variability in risk for developing DM among PWCs that are homozygous for the disease-related SOD1 mutation. Further studies are warranted to clarify the effect of this modifier across dog breeds. PMID- 27185957 TI - Disease-modifying anti-rheumatic drugs and non-melanoma skin cancer in inflammatory arthritis patients: a retrospective cohort study. AB - OBJECTIVES: The aim was to determine the non-melanoma skin cancer (NMSC) risk in patients with RA or PsA exposed to MTX and other DMARDs. METHODS: Information on medication was collected on 405 patients with RA or PsA in two private rheumatology practices and was matched to comprehensive histologically confirmed cancer registry data for the years 1978-2005. Relative risks (RRs) were estimated by logarithmic binomial modelling, and standardized incidence ratios (SIRs) were calculated from year-, sex- and age-specific rates of NMSC for the local population. RESULTS: Compared with no MTX usage, any MTX usage was associated with a higher rate of at least one histopathologically confirmed NMSC (SIR 4.64, 95% CI: 0.67, 33.2). The SIR was 4.81 (95% CI: 3.60, 6.29) for those receiving a cumulative dose >8000 mg compared with SIR 2.31 (95% CI: 1.58, 2.36) for <5000 mg. An increased risk was shown for both basal cell carcinomas and squamous cell carcinomas, with an apparent dose-response relationship for basal cell carcinomas but not for squamous cell carcinomas. There was an increased risk of NMSC in patients taking CSA (RR = 2.51, 95% CI: 1.23, 5.13) and D-Pen (RR 3.49, 95% CI: 1.34, 4.63) in addition to MTX, but not for patients taking AZA or LEF. CONCLUSION: MTX, and concurrent MTX and CSA or D-Pen use, is associated with an increased risk of NMSC. These results should encourage greater clinical vigilance for NMSC in treated patients with RA and PsA. PMID- 27185959 TI - Characterizing the correlations between local phase fractions of gas-liquid two phase flow with wire-mesh sensor. AB - Understanding of flow patterns and their transitions is significant to uncover the flow mechanics of two-phase flow. The local phase distribution and its fluctuations contain rich information regarding the flow structures. A wire-mesh sensor (WMS) was used to study the local phase fluctuations of horizontal gas liquid two-phase flow, which was verified through comparing the reconstructed three-dimensional flow structure with photographs taken during the experiments. Each crossing point of the WMS is treated as a node, so the measurement on each node is the phase fraction in this local area. An undirected and unweighted flow pattern network was established based on connections that are formed by cross correlating the time series of each node under different flow patterns. The structure of the flow pattern network reveals the relationship of the phase fluctuations at each node during flow pattern transition, which is then quantified by introducing the topological index of the complex network. The proposed analysis method using the WMS not only provides three-dimensional visualizations of the gas-liquid two-phase flow, but is also a thorough analysis for the structure of flow patterns and the characteristics of flow pattern transition. This article is part of the themed issue 'Supersensing through industrial process tomography'. PMID- 27185958 TI - The relationship between three-dimensional knee MRI bone shape and total knee replacement-a case control study: data from the Osteoarthritis Initiative. AB - OBJECTIVE: There is growing understanding of the importance of bone in OA. Our aim was to determine the relationship between 3D MRI bone shape and total knee replacement (TKR). METHODS: A nested case-control study within the Osteoarthritis Initiative cohort identified case knees with confirmed TKR for OA and controls that were matched using propensity scores. Active appearance modelling quantification of the bone shape of all knee bones identified vectors between knees having or not having OA. Vectors were scaled such that -1 and +1 represented the mean non-OA and mean OA shapes. RESULTS: Compared to controls (n = 310), TKR cases (n = 310) had a more positive mean baseline 3D bone shape vector, indicating more advanced structural OA, for the femur [mean 0.98 vs 0.11; difference (95% CI) 1.10 (0.88, 1.31)], tibia [mean 0.86 vs -0.07; difference (95% CI) 0.94 (0.72, 1.16)] and patella [mean 0.95 vs 0.03; difference (95% CI) 0.92 (0.65, 1.20)]. Odds ratios (95% CI) for TKR per normalized unit of 3D bone shape vector for the femur, tibia and patella were: 1.85 (1.59, 2.16), 1.64 (1.42, 1.89) and 1.36 (1.22, 1.50), respectively, all P < 0.001. After including Kellgren-Lawrence grade in a multivariable analysis, only the femur 3D shape vector remained significantly associated with TKR [odds ratio 1.24 (1.02, 1.51)]. CONCLUSION: 3D bone shape was associated with the endpoint of this study, TKR, with femoral shape being most associated. This study contributes to the validation of quantitative MRI bone biomarkers for OA structure-modification trials. PMID- 27185960 TI - Interface and permittivity simultaneous reconstruction in electrical capacitance tomography based on boundary and finite-elements coupling method. AB - Electrical capacitance tomography (ECT) is a non-destructive detection technique for imaging the permittivity distributions inside an observed domain from the capacitances measurements on its boundary. Owing to its advantages of non contact, non-radiation, high speed and low cost, ECT is promising in the measurements of many industrial or biological processes. However, in the practical industrial or biological systems, a deposit is normally seen in the inner wall of its pipe or vessel. As the actual region of interest (ROI) of ECT is surrounded by the deposit layer, the capacitance measurements become weakly sensitive to the permittivity perturbation occurring at the ROI. When there is a major permittivity difference between the deposit and the ROI, this kind of shielding effect is significant, and the permittivity reconstruction becomes challenging. To deal with the issue, an interface and permittivity simultaneous reconstruction approach is proposed. Both the permittivity at the ROI and the geometry of the deposit layer are recovered using the block coordinate descent method. The boundary and finite-elements coupling method is employed to improve the computational efficiency. The performance of the proposed method is evaluated with the simulation tests. This article is part of the themed issue 'Supersensing through industrial process tomography'. PMID- 27185962 TI - Sensing flame structure by process tomography. AB - Non-intrusive visualization of the structure of flames can offer us many advantages in studying the reaction mechanisms of combustion and observing special distributions of the parameters required for the development of equipment such as jet engines and gas turbines. Process tomography is a relatively new technique for such a task, but is useful owing to its fast speed and capability of detecting signals related to ionizations caused by chemical reactions and thermal effects. Electric capacitance tomography (ECT) is one of the process tomographic techniques. ECT usually comprises a sensor array of electrodes that detect permittivity variations in the measuring zone, a data-logging device and a computer that controls data acquisition and carries out image reconstruction. There have been studies on ECT imaging of flames; however, ECT has not been exploited sufficiently to reveal the inner structure of the flames. In this study, a sensor with planar electrodes is created, and the associated three dimensional sensitivity map is generated by the finite-element method to detect flame structure. A series of experiments are carried out covering a range of feed rates of fuel and air. Data are collected by the ECT sensor and hardware. The results of the ECT reconstruction show good agreement with actual features, and the structure of the flame is found. This opens up a new route for the study of flames. This article is part of the themed issue 'Supersensing through industrial process tomography'. PMID- 27185961 TI - Reconstruction of velocity fields in electromagnetic flow tomography. AB - Electromagnetic flow meters (EMFMs) are the gold standard in measuring flow velocity in process industry. The flow meters can measure the mean flow velocity of conductive liquids and slurries. A drawback of this approach is that the velocity field cannot be determined. Asymmetric axial flows, often encountered in multiphase flows, pipe elbows and T-junctions, are problematic and can lead to serious systematic errors. Recently, electromagnetic flow tomography (EMFT) has been proposed for measuring velocity fields using several coils and a set of electrodes attached to the surface of the pipe. In this work, a velocity field reconstruction method for EMFT is proposed. The method uses a previously developed finite-element-based computational forward model for computing boundary voltages and a Bayesian framework for inverse problems. In the approach, the vz component of the velocity field along the longitudinal axis of the pipe is estimated on the pipe cross section. Different asymmetric velocity fields encountered near pipe elbows, solids-in-water flows in inclined pipes and in stratified or multiphase flows are tested. The results suggest that the proposed reconstruction method could be used to estimate velocity fields in complicated pipe flows in which the conventional EMFMs have limited accuracy. This article is part of the themed issue 'Supersensing through industrial process tomography'. PMID- 27185963 TI - A gradiometric version of contactless inductive flow tomography: theory and first applications. AB - The contactless inductive flow tomography (CIFT) is a measurement technique that allows reconstructing the flow of electrically conducting fluids by measuring the flow-induced perturbations of one or various applied magnetic fields and solving the underlying inverse problem. One of the most promising application fields of CIFT is the continuous casting of steel, for which the online monitoring of the flow in the mould would be highly desirable. In previous experiments at a small scale model of continuous casting, CIFT has been applied to various industrially relevant problems, including the sudden changes of flow structures in case of argon injection and the influence of a magnetic stirrer at the submerged entry nozzle. The application of CIFT in the presence of electromagnetic brakes, which are widely used to stabilize the flow in the mould, has turned out to be more challenging due to the extreme dynamic range between the strong applied brake field and the weak flow-induced perturbations of the measuring field. In this paper, we present a gradiometric version of CIFT, relying on gradiometric field measurements, that is capable to overcome those problems and which seems, therefore, a promising candidate for applying CIFT in the steel casting industry. This article is part of the themed issue 'Supersensing through industrial process tomography'. PMID- 27185964 TI - Electronic hardware design of electrical capacitance tomography systems. AB - Electrical tomography techniques for process imaging are very prominent for industrial applications, such as the oil and gas industry and chemical refineries, owing to their ability to provide the flow regime of a flowing fluid within a relatively high throughput. Among the various techniques, electrical capacitance tomography (ECT) is gaining popularity due to its non-invasive nature and its capability to differentiate between different phases based on their permittivity distribution. In recent years, several hardware designs have been provided for ECT systems that have improved its resolution of measurements to be around attofarads (aF, 10(-18) F), or the number of channels, that is required to be large for some applications that require a significant amount of data. In terms of image acquisition time, some recent systems could achieve a throughput of a few hundred frames per second, while data processing time could be achieved in only a few milliseconds per frame. This paper outlines the concept and main features of the most recent front-end and back-end electronic circuits dedicated for ECT systems. In this paper, multiple-excitation capacitance polling, a front end electronic technique, shows promising results for ECT systems to acquire fast data acquisition speeds. A highly parallel field-programmable gate array (FPGA) based architecture for a fast reconstruction algorithm is also described. This article is part of the themed issue 'Supersensing through industrial process tomography'. PMID- 27185966 TI - Multiphase permittivity imaging using absolute value electrical capacitance tomography data and a level set algorithm. AB - Multiphase flow imaging is a very challenging and critical topic in industrial process tomography. In this article, simulation and experimental results of reconstructing the permittivity profile of multiphase material from data collected in electrical capacitance tomography (ECT) are presented. A multiphase narrowband level set algorithm is developed to reconstruct the interfaces between three- or four-phase permittivity values. The level set algorithm is capable of imaging multiphase permittivity by using one set of ECT measurement data, so called absolute value ECT reconstruction, and this is tested with high-contrast and low-contrast multiphase data. Simulation and experimental results showed the superiority of this algorithm over classical pixel-based image reconstruction methods. The multiphase level set algorithm and absolute ECT reconstruction are presented for the first time, to the best of our knowledge, in this paper and critically evaluated. This article is part of the themed issue 'Supersensing through industrial process tomography'. PMID- 27185965 TI - Super-sensing through industrial process tomography. AB - In this introduction article, we present a brief overview of industrial process tomography. This will start by linking between the concept of industrial process tomography and super-sensing. This will follow with a brief introduction to various process tomography systems and in particular electrical tomography methods. This article is part of the themed issue 'Supersensing through industrial process tomography'. PMID- 27185967 TI - Super-sensing technology: industrial applications and future challenges of electrical tomography. AB - Electrical tomography is a relatively new imaging technique that can image the distribution of the passive electrical properties of an object. Since electrical tomography technology was proposed in the 1980s, the technique has evolved rapidly because of its low cost, easy scale-up and non-invasive features. The technique itself can be sensitive to all passive electrical properties, such as conductivity, permittivity and permeability. Hence, it has a huge potential to be applied in many applications. Owing to its ill-posed nature and low image resolution, electrical tomography attracts more attention in industrial fields than biomedical fields. In the past decades, there have been many research developments and industrial implementations of electrical tomography; nevertheless, the awareness of this technology in industrial sectors is still one of the biggest limitations for technology implementation. In this paper, the authors have summarized several representative applications that use electrical tomography. Some of the current tomography research activities will also be discussed. This article is part of the themed issue 'Supersensing through industrial process tomography'. PMID- 27185968 TI - Arts of electrical impedance tomographic sensing. AB - This paper reviews governing theorems in electrical impedance sensing for analysing the relationships of boundary voltages obtained from different sensing strategies. It reports that both the boundary voltage values and the associated sensitivity matrix of an alternative sensing strategy can be derived from a set of full independent measurements and sensitivity matrix obtained from other sensing strategy. A new sensing method for regional imaging with limited measurements is reported. It also proves that the sensitivity coefficient back projection algorithm does not always work for all sensing strategies, unless the diagonal elements of the transformed matrix, A(T)A, have significant values and can be approximate to a diagonal matrix. Imaging capabilities of few sensing strategies were verified with static set-ups, which suggest the adjacent electrode pair sensing strategy displays better performance compared with the diametrically opposite protocol, with both the back-projection and multi-step image reconstruction methods. An application of electrical impedance tomography for sensing gas in water two-phase flows is demonstrated. This article is part of the themed issue 'Supersensing through industrial process tomography'. PMID- 27185969 TI - The Main and Interactive Effects of Maternal Interpersonal Emotion Regulation and Negative Affect on Adolescent Girls' Borderline Personality Disorder Symptoms. AB - The transaction of adolescent's expressed negative affect and parental interpersonal emotion regulation are theoretically implicated in the development of borderline personality disorder (BPD). Although problem solving and support/validation are interpersonal strategies that foster emotion regulation, little is known about whether these strategies are associated with less BPD severity among adolescents. Adolescent girls (age 16; N = 74) and their mothers completed a conflict discussion task, and maternal problem solving, support/validation, and girls' negative affect were coded. Girls' BPD symptoms were assessed at four time points. A 3-way interaction of girls' negative affect, problem solving, and support/validation indicated that girls' negative affect was only associated with BPD severity in the context of low maternal support/validation and high maternal problem solving. These variables did not predict changes in BPD symptoms over time. Although high negative affect is a risk for BPD severity in adolescent girls, maternal interpersonal emotion regulation strategies moderate this link. Whereas maternal problem solving coupled with low support/validation is associated with a stronger negative affect BPD relation, maternal problem solving paired with high support/validation is associated with an attenuated relationship. PMID- 27185970 TI - Feature Augmentation via Nonparametrics and Selection (FANS) in High-Dimensional Classification. AB - We propose a high dimensional classification method that involves nonparametric feature augmentation. Knowing that marginal density ratios are the most powerful univariate classifiers, we use the ratio estimates to transform the original feature measurements. Subsequently, penalized logistic regression is invoked, taking as input the newly transformed or augmented features. This procedure trains models equipped with local complexity and global simplicity, thereby avoiding the curse of dimensionality while creating a flexible nonlinear decision boundary. The resulting method is called Feature Augmentation via Nonparametrics and Selection (FANS). We motivate FANS by generalizing the Naive Bayes model, writing the log ratio of joint densities as a linear combination of those of marginal densities. It is related to generalized additive models, but has better interpretability and computability. Risk bounds are developed for FANS. In numerical analysis, FANS is compared with competing methods, so as to provide a guideline on its best application domain. Real data analysis demonstrates that FANS performs very competitively on benchmark email spam and gene expression data sets. Moreover, FANS is implemented by an extremely fast algorithm through parallel computing. PMID- 27185971 TI - Comparison of the depth of tissue necrosis between double-freeze and single freeze nitrous oxide-based cryotherapy. AB - BACKGROUND: Cryotherapy is one the methods of treating cervical premalignant lesions. It is particularly suitable for low-resource countries because of it is relative cheaper, has low cost of maintenance, ease of use and that does not require electricity which is in short supply in many rural areas of developing countries where the incidence and mortality from cervical cancer is very high. In this study we compared single and double freezing on the cervices of women admitted for hysterectomy for benign conditions using Nitrous-based cryotherapy. MATERIALS AND METHODS: Patients admitted for elective hysterectomy for benign gynaecological conditions were randomized into two arms. The first group had single freeze cryotherapy while the second arm received double freeze cryotherapy. The cervices were examined 24 hours later to determine the depth of tissue necrosis. RESULTS: In this comparative study, the depth of tissue necrosis was deeper with double freeze compared with single freeze. Also in both arms, the depth of necrosis was deeper on anterior lips than on posterior lips of the cervix. CONCLUSION: Double freeze technique achieve more depth of tissue necrosis than single-freeze on both anterior and posterior lips of the cervix. PMID- 27185972 TI - Effect of current glycemic control on qualitative body composition in sedentary ambulatory Type 2 diabetics. AB - BACKGROUND: Obesity and Type 2 diabetes mellitus are on rise with cause-effect relationship. Diabetics monitor blood sugar, neglecting qualitative body composition, leaving residual threat of ectopic fat unattended. We tried to correlate glycemic triad with parameters of body composition derived objectively by bioelectrical impedance analysis (BIA). MATERIALS AND METHODS: A sample of 78 under treatment sedentary Type 2 diabetics of either sex with known glycemic and lipidemic control from our city. Following baseline assessment measurement was done by instrument Omron Karada Scan (Model HBF-510, China) using the principle of tetra poplar BIA to derive parameters of body composition. We tried to correlate glycemic triad with these parameters, both directly as well as after defining them as per established cutoff norms. RESULTS: We found poor glycemic control in the study group (20% for Hb1AC), high body mass index, subcutaneous fat, visceral fat (VF), total body fat (TBF), and lesser mass of skeletal muscle in Type 2 diabetics. However, there were small, insignificant, and inconsistent difference of these parameters while directly correlating with the fasting blood sugar, postprandial blood sugar, and glycosylated hemoglobin. On qualitative assessment, the impact of glycemic control as per standard norms, the risk of high VF, high TBF, low skeletal muscle mass was though high (between 1 and 2) in Type 2 diabetics with poor glycemic control as compared to good glycemics, but each strength lacks statistical significance. CONCLUSION: BIA reveals that Type 2 diabetics have more ectopic fat on expense of skeletal muscle that do not correlate with current glycemic status, both quantitatively and qualitatively. Measurement of body composition can be included and subjects can be motivated for lifestyle modification strategies while managing metabolic derangements of Type 2 diabetes. PMID- 27185973 TI - Psychosocial needs of families of intensive care patients: Perceptions of nurses and families. AB - BACKGROUND: Admission to an intensive care unit (ICU) is not only stressful to the patients but the patients' family members. Families are believed not to receive their required attention because their needs are incorrectly and inaccurately evaluated by the health care team. Therefore, the present study aimed to examine the perceptions of ICU nurses and families regarding the psychosocial needs of families of intensive care patients. MATERIALS AND METHODS: This descriptive-analytical study was conducted on a randomly selected population of 80 nurses and 80 family members of ICU patients. Data were collected using a two-part questionnaire containing sociodemographic characteristics and the Critical Care Family Need Inventory (CCFNI). RESULTS: The rank order of the five most important CCFNI item needs identified by families were as follows: "To feel that the hospital personnel care about the patient", "to be assured that the best care possible is being given to the patient", "to have questions answered honestly", "to know specific facts concerning patient's progress", and "to be called at home about changes in the patient's condition." The top five CCFNI item needs identified by nurses were in the following order: "To be assured that the best care possible is being given to the patient", "to be told about transfer plans while they are being made", "to feel that the hospital personnel care about the patient", "to have questions answered honestly", and "to know specific facts concerning patient's progress." CONCLUSION: The present study showed there are similarities and dissimilarities between nurses and family members in their perceived importance of some family needs in the ICU. It can thus be inferred from our results that the participating nurses misestimated the needs of family members, attested by their wrong estimation of the most need statements. PMID- 27185974 TI - Management of ovarian cysts with percutaneous aspiration and methotrexate injection. AB - BACKGROUND: To evaluate ultrasonographic-guided cyst aspiration and methotrexate injection in the management of simple and endometriotic ovarian cysts in selected patients. SUBJECTS AND METHODS: This prospective study was conducted in the Department of Obstetrics and Gynaecology in Government Medical College and Hospital, Chandigarh, from November 2007 to October 2009. It included 132 female patients (age range, 15-72 years; mean, 38.7 years) with simple or endometriotic ovarian cysts (3.0-10.6 cm) at ultrasonic examinations. We performed puncture and aspiration followed by methotrexate injection into the cyst. All patients were followed for 12 months. None was lost to follow-up. RESULTS: At follow-up ultrasonography, cysts had disappeared in 120 patients (90.90%) and persisted in 12 patients (9%). No major complications were observed in our study population during or after the procedure. Only 10 patients reported mild pelvic pain, and four others reported dizziness or nausea during or after the procedure. Malignant cells were not found in any of the cases at cytologic examination. We did not observe any cases of infection after the procedure. CONCLUSION: Ultrasonography guided transabdominal aspiration of cyst fluid and subsequent methotrexate injection appears to be an alternative treatment for both simple and endometriotic ovarian cysts in selected cases. PMID- 27185975 TI - The predictors of psychiatric disorders among people living with epilepsy as seen in a Nigerian Tertiary Health Institution. AB - BACKGROUND: Mental disorders may complicate epilepsy which can further impair the quality of life of people living with this chronic neurological condition. The aim of this study was to determine the types of psychiatric disorders in patients with epilepsy and to determine the sociodemographic and clinical factors that may predict these psychiatric illnesses. MATERIALS AND METHODS: This is a descriptive cross-sectional study carried out over a period of 6 months at Abubakar Tafawa Balewa University Teaching Hospital, Bauchi, Nigeria. The Mini International Neuropsychiatric Interview was used to determine the psychological health of 74 consecutively recruited adult patients with epilepsy attending the psychiatric outpatients' clinic of the hospital. Psychiatric diagnoses were based on Diagnostic and Statistical Manual for Mental Disorders, 4(th) Edition criteria, and logistic regression analysis was done to determine variables that predict psychiatric disorder. RESULTS: Majority of the participants were male (67.6%) with their age ranging from 18 to 68 years and the mean age of 30.55 +/- 10.91 years. Thirty-three (44.6%) of our study respondents had psychiatric diagnoses that included major depressive disorder (21.6%), schizophrenia (17.6%), generalized anxiety disorder (4.1%), and hypomania (1.4%). Being unemployed (odds ratio [OR] = 3.24. 95% confidence interval [CI] = 1.15-9.10, P = 0.026) and short term seizure free period (OR = 0.19, 95% CI = 0.04-0.78, P = 0.022) were the variables found to be predictive of psychiatric diagnoses. CONCLUSIONS: The study revealed that a large percentage of people living with epilepsy develop mental disorders which can further increase the burden and worsen the quality of life of patients with this chronic debilitating condition. PMID- 27185976 TI - Ascorbic acid treatment elevates follicle stimulating hormone and testosterone plasma levels and enhances sperm quality in albino Wistar rats. AB - BACKGROUND: Infertility issues have been linked to the effect of oxidative reaction in the reproductive system. This study evaluated the effect of ascorbic acid, on fertility parameters of male albino Wistar rats was studied. MATERIALS AND METHODS: Eighteen albino Wistar rats weighed between 178 g and 241 g were used, randomly assigned into three groups. Group 1 was the control group; oral gavaged 5 ml of distilled water; Groups 2 and 3 were administered medium dose (250 mg/kg) and high dose of ascorbic acid (400 mg/kg), respectively; twice daily for 21 days. Blood samples were obtained by cardiac puncture, and blood serum was obtained for hormonal assay, and the testes were harvested for sperm analysis. RESULTS: Follicle stimulating hormone levels significantly increased in the high dose group as compared to both the control and medium dose groups. Luteinizing hormone levels in the medium dose group decreased significantly as compared to the control group. Testosterone significantly increased in both the medium- and high-dose groups as compared to the control group. Sperm motility increased significantly in the high-dose group as compared to both control and medium-dose groups. Percentage sperm concentration decreased significantly in the medium-dose group when compared to the control and increased significantly in the high-dose group as compared to the medium-dose group. For percentage normal morphology, there was a dose-dependent increase in the test groups when compared to control group. CONCLUSION: These results are indicative of a positive influence of ascorbic acid on male fertility modulators and may therefore, serve as a potential adjuvant treatment for male infertility cases. PMID- 27185977 TI - Assessment of maternal risk factors associated with low birth weight neonates at a tertiary hospital, Nanded, Maharashtra. AB - BACKGROUND: To assess the maternal risk factors associated with low birth weight (LBW) neonates at a tertiary hospital, Nanded, Maharashtra. MATERIALS AND METHODS: This study was carried out in a tertiary care hospital in Nanded city of Maharashtra between January 2014 and July 2014 among 160 cases (LBW-birth weight <=2499 g) and 160 controls (normal birth weight-birth weight >2499. Data collection was done by using predesigned questionnaire and also related health documents were checked and collected the expected information during the interview after obtaining informed consent from mothers. The data were analyzed by Epi Info 7 Version. RESULTS: The present study found the significant association among gestational age, sex of baby, type of delivery, maternal age, religion, education of mother and husband, occupation of mother and husband, type of family, maternal height, weight gain, hemoglobin level, planned/unplanned delivery, bad obstetric history, interval between pregnancies, previous history of LBW, underlying disease, tobacco chewing, timing of first antenatal care (ANC) visit, total number of ANC visit, and iron and folic acid (IFA) tablets consumption with LBW. No significant association was found among maternal age, residence, caste, consanguinity of marriage, socioeconomic status, gravida, birth order, multiple pregnancy, and smoking with LBW in our study. CONCLUSION: It was concluded that hemoglobin level, weight gain during pregnancy, gestational age, planned/unplanned delivery, bad obstetric history, and IFA tablets consumption during pregnancy were independent risk factors for LBW. PMID- 27185978 TI - Cost-effectiveness of extracorporeal shock wave lithotripsy in a poor resource setting: The Okada, Nigeria experience. AB - BACKGROUND: The first extracorporeal shock wave lithotripsy (ESWL) used in Nigeria was at Igbinedion Hospital and Medical Research Centre (IHMRC), Okada in 1992 and it functioned for 6 consecutive years. The objectives of this study were to analyze the cost-effectiveness of the procedure and highlight the associated factors that led to its failure. METHODS: A retrospective study of medical records and publications associated with the use of ESWL at IHMRC, Okada, for the period of 1992 to 1998. The study was conducted between January 2003 and November 2008. Unclassified authentic information relating to the use of ESWL and treatment of upper urinary tract stones was obtained from the IHMRC Okada and some government hospitals on hospital bills. Relevant documents in public domains related to the national and international wages and emoluments of medical workers and socioeconomic development of Nigeria within the time the ESWL functioned were studied. RESULT: A total of 32 patients were treated with 51 treatment sessions which is an average of nine patients per year and an average of two treatment sessions per patient were involved. The reasons for the low patronage were the extremely low stone formation rate of Nigerians, poverty, and out-of-pocket payment system. In addition, each treatment session of ESWL at Okada cost an average of $681.8 compared to $227.3 for open nephrolithotomy in a nearby high profile teaching hospital. The IHMRC, Okada, paid an average annual salary of ?180,000 ($8,181.8) for each medical consultant compared to ?120,000 ($5,454.5) paid by federal teaching hospitals in Nigeria within the period. Expatriate consultant doctors from Europe and USA who initially manned the lithotriptor at IHMRC, Okada, were paid much higher salaries. Average annual income of $5,909 for each of the 6 years amounting to a total of $34,771.7 for the six years was realized which could not maintain staff salaries in the hospital leading to staff emigration, decline of the hospital services, and eventual closure of the ESWL procedure center in the hospital in 1998. CONCLUSION: ESWL at Okada was not cost effective both to patients and the hospital management. Despite these, ESWL is desirable in poor-resource countries because of its noninvasiveness, low morbidity, and usability in patients who are unfit for open surgery. Purchasing high technological medical equipment as commodities by sub-Saharan Africans without considering the prevalence of diseases they are meant to cater for, their maintenance for steady function during useful lifespan, their cost-effectiveness and how to recoup the money spent on investments depletes the scarce foreign exchange reserve of the home countries and is eventually counterproductive as exemplified by this case. PMID- 27185979 TI - Quality of life among human immunodeficiency virus-1 infected and human immunodeficiency virus-1/hepatitis C virus co-infected individuals in Iranian patients. AB - BACKGROUND: The aim of this study was to compare the quality of life (QOL) of people infected with both hepatitis C virus (HCV) and human immunodeficiency virus (HIV). The study design was a cross sectional descriptive survey, using self administered questionnaires. MATERIALS AND METHODS: A convenience sample of 242 patients (131 of them HIV/HCV), Iranian adults (aged 18-57) living with HIV/AIDS, was recruited from outpatient referring to Imam Khomeini Hospital behavioral counseling center in Tehran city, Iran. The instruments included the Multidimensional QOL HIV (MQoL HIV) and a demographic section. RESULTS: The majority of the samples were male and single. The mean age was 36.52 years (standard deviation = 8.5). HIV mono infected patients reported higher scores in social support and physical functioning, but lower scores in physical health compared with HIV/HCV co infected individuals. There was no significant difference in overall MQOL HIV score between HIV and HIV/HCV patients. CONCLUSION: Future studies will need to explore the impact of HCV on HIV infected individuals' QOL. PMID- 27185980 TI - Immunohistochemical profile of uterine leiomyomas; a comparison between different subtypes. AB - BACKGROUND: Of all Smooth muscle tumours originating from uterus are leiomyomas are the most common ones. Benign nature and smooth muscle origination of leiomyomas can be easily documented via histological examination. In present study it was tried to examine immunohistochemical profile of leiomyomas with different subtypes. MATERIAL AND METHODS: In this cross-sectional study 64 cases of smooth muscle tumors originating from uterus were included in study. As a control group 12 cases of conventional leiomyomas were selected. Then estrogen receptor, progesterone receptor, p53 and ki-67 were assessed. Statistical analysis was conducted using SPSS 16.0. RESULTS: P 53 and ki-67 antibody status was diffusely positive in 12 out of 24 cases (50%) of leiomyosarcomas. Leiomyomas with bizzare nuclei were stained with Ki67 proliferative marker less than those in obviously malignant cases (P < 0.001). Estrogen and progesterone receptors had a reverse correlation with tumours malignancy potential. CONCLUSION: Since p53 is known as an important inhibitory trigger for proliferative cycle of cells, in current study it was concluded that p53 inhibitory role decreases as malignancy potential increases, also tumors dependence on steroids via steroid receptors decreases as malignancy potential increases. PMID- 27185981 TI - Intraventricular cerebrospinal fluid pulsation artifacts on low-field magnetic resonance imaging: Potential pitfall in diagnosis? AB - BACKGROUND: Intraventricular cerebrospinal fluid (CSF) pulsation artifact can pose a diagnostic problem in fluid-attenuated inversion recovery (FLAIR) brain magnetic resonance images (MRI) appearing as intraventricular hyperintensity. The extent of this challenge among radiologists in Africa using low-field MRI systems is relatively sparsely documented in the literature. The purpose of this study was to identify the presence and frequency of ventricular CSF pulsation artifact (VCSFA) on FLAIR axial brain images with a low-field MR system. MATERIALS AND METHODS: FLAIR axial images were obtained on a low-field 0.3T unit (6000 ms/108 ms/2 [repetition time/echo time/excitations], inversion time = 1700 ms, field of view = 28 cm, matrix = 195 * 256, and 6 mm contiguous sections). Two experienced radiologists independently rated VCSFA in the lateral, third, and fourth ventricles in 202 consecutive patients (age range 1-100 years) referred for brain MR for various indications. We reviewed the pattern of artifacts, to determine its relationship to age, gender, and third ventricular size. RESULTS: The low field FLAIR MR brain images of 33 patients (16.3%) showed VCSFA in at least one ventricular cavity. The fourth ventricle was the most common site of VCSFA (n = 10), followed by the third ventricle (n = 8) and the lateral ventricles (n = 7). Eight patients had VCSFA in multiple locations, one of them in all ventricles. A smaller third ventricular size and, to a lesser extent, younger age was significantly associated with VCSFA. CSF Pulsation of VCSFA did not occur across the brain parenchyma in the phase encoding direction. CONCLUSION: VCSFA may mimic pathology on low-field axial FLAIR brain images and are more common in young patients with smaller ventricular size. Although these artifacts are less frequently observed at lower magnetic field strengths, their recognition on low field MRI systems is important in avoiding a misdiagnosis. PMID- 27185982 TI - Plasma levels of inflammatory cytokines in adult Nigerians with the metabolic syndrome. AB - BACKGROUND: The aim of this study is to determine the plasma levels of interleukin 6 (IL-6), tumor necrotic factor alpha (TNF-alpha, and C-reactive protein (CRP) in adult Nigerians with the metabolic syndrome and to determine the relationship between components of the metabolic syndrome and CRP in adult Nigerians. SUBJECTS AND METHODS: This was a case-control study of fifty adult men and women with the metabolic syndrome, and fifty age- and sex-matched males and females without the metabolic syndrome. Metabolic syndrome was defined based on the National Cholesterol Education Programme-Adult Treatment Panel III criteria. Written informed consent was obtained from the participants. Blood pressure and anthropometry measurements were taken and venous blood was collected after an overnight fast. The Ethics Committee of the Lagos University Teaching Hospital, Lagos, Nigeria, approved the study protocol. Comparisons of continuous variables and categorical variables were done using the Student's t-test and Chi-square test, respectively. Regression analysis was used to determine the associations between variables. Statistical significance was set at P< 0.05. RESULTS: The age- and sex-matched males and females with and without the metabolic syndrome did not differ in their sociodemographic characteristics. They however differed in some clinical and laboratory parameters such as diastolic blood pressure (P = 0.048), waist circumference (P = 0.002), body mass index (P = 0.012), waist/hip ratio (P = 0.023), high density lipoprotein (HDL) (P = 0.012), and insulin resistance (IR) (P = 0.042). There was a statistically significant increase in the inflammatory marker, CRP (P = 0.019), the cytokines, IL6 (P = 0.040), and TNF-alpha (P = 0.031) between the subjects with and without metabolic syndrome. There was also a significant association between CRP, waist circumference, IR, and HDL in the metabolic syndrome (P < 0.05). CONCLUSION: Plasma levels of inflammatory cytokines are raised in metabolic syndrome and this may provide novel strategies for the management of metabolic syndrome and related disorders. PMID- 27185983 TI - Effects of adenotonsillar hypertrophy corrective surgery on nocturnal enuresis of children. AB - BACKGROUND: Nocturnal enuresis is considered a common urological complaint especially among children. Respiratory obstructive diseases have been one of the possible etiologies of such a condition. The most common type of upper respiratory obstructive diseases in childhood is adenotonsillar hypertrophy. In this study, it was tried to estimate the prevalence of nocturnal enuresis in adenotonsillar hypertrophy as an upper obstructive airway disease and cure rate after corrective operation. MATERIALS AND METHODS: In this longitudinal study, 184 children with adenotonsillar hypertrophy as case group and 200 healthy children as control group were randomly compared for nocturnal enuresis incidence and risk factors. Then they were followed after 6 months to estimate the cure rate after corrective operation. RESULTS: In case group, nocturnal enuresis was more common than control group (26% vs. 17%, P = 0.1). Factors which had a role in enuresis in case group were family history (P = 0.03) and male sex (P = 0.05). Three months after surgery, 48% of children totally cured from enuresis (P = 0.001) and 71% cured both partially or totally (P = 0.03). The response rate after moderate obstruction relieving was 100% while that in severe cases was 60% (P = 0.2). CONCLUSIONS: Nocturnal enuresis due to upper obstructive airway disease occurs more in male and in the presence of family history. The cure rate after 6 months of operation was more prominent in moderate obstruction which suggests enuresis in severe airway obstruction may need a longer time to subside. Cure rate of primary enuresis due to obstructive airway disease after 6 months of relieving was 48% in children over 5 years old. PMID- 27185984 TI - Ovarian hyperstimulation syndrome in a spontaneous pregnancy: A potential for missed-diagnosis. AB - Ovarian hyperstimulation syndrome (OHSS) with the natural ovulatory cycle is extremely rare. We report a case of severe OHSS associated with a spontaneous normal singleton pregnancy in a 23-year-old woman presenting with severe abdominal pain, vomiting, and dyspnea. Ultrasonography revealed 10 weeks viable intra-uterine single fetus with bilateral multilocular cystic ovarian masses and ascites. She had supportive therapy inclusive of oral bromocriptine with complete resolution of OHSS and an eventual uncomplicated normal vaginal delivery at 39 weeks of pregnancy. PMID- 27185985 TI - Existence of constants in regular splicing languages. AB - In spite of wide investigations of finite splicing systems in formal language theory, basic questions, such as their characterization, remain unsolved. It has been conjectured that a necessary condition for a regular language L to be a splicing language is that L must have a constant in the Schutzenberger sense. We prove this longstanding conjecture to be true. The result is based on properties of strongly connected components of the minimal deterministic finite state automaton for a regular splicing language. Using constants of the corresponding languages, we also provide properties of transitive automata and pathautomata. PMID- 27185986 TI - Tuberculosis therapy in Mumbai: Critical importance of drug-susceptibility testing. PMID- 27185987 TI - Possible impact of the standardized Category IV regimen on multidrug-resistant tuberculosis patients in Mumbai. AB - BACKGROUND: Treatment of multidrug-resistant tuberculosis (MDR-TB) in the Programmatic Management of Drug-resistant TB program involves a standard regimen with a 6-month intensive phase and an 18-month continuation phase. However, the local drug resistance patterns in high MDR regions such as Mumbai may not be adequately reflected in the design of the regimen for that particular area. SETTING: The study was carried out at a private Tertiary Level Hospital in Mumbai in a mycobacteriology laboratory equipped to perform the second-line drug susceptibility testing (DST). OBJECTIVE: We attempted to analyze the impact of prescribing the standardized Category IV regimen to all patients receiving a DST at our mycobacteriology laboratory. MATERIALS AND METHODS: All samples confirmed to be MDR-TB and tested for the second-line drugs at Hinduja Hospital's Mycobacteriology Laboratory in the year 2012 were analyzed. RESULTS: A total of 1539 samples were analyzed. Of these, 464 (30.14%) were MDR-TB, 867 (56.33%) were MDR with fluoroquinolone resistance, and 198 (12.8%) were extensively drug resistant TB. The average number of susceptible drugs per sample was 3.07 +/- 1.29 (assuming 100% cycloserine susceptibility). Taking 4 effective drugs to be the cut or an effective regimen, the number of patients receiving 4 or more effective drugs from the standardized directly observed treatment, short-course plus regimen would be 516 (33.5%) while 66.5% of cases would receive 3 or less effective drugs. CONCLUSION: Our study shows that a high proportion of patients will have resistance to a number of the first- and second-line drugs. Local epidemiology must be factored in to avoid amplification of resistance. PMID- 27185989 TI - Management of chronic empyema with unexpandable lung in poor surgical risk patients using an empyema tube. AB - OBJECTIVES: High preoperative risk precludes decortication and other surgical interventions in some patients with chronic empyema. We manage such patients by converting the chest tube into an "empyema tube," cutting the tube near the skin and securing the end with a sterile clip to allow for open pleural drainage. The patient is followed serially, and the tube gradually withdrawn based on radiological resolution and amount of drainage. METHODS: Between 2010 and 2014, patients with chronic empyema and unexpandable lung, deemed high-risk surgical candidates, had staged chest tube removal, and were included for the study. The volume of fluid drained, culture results, duration of drainage, functional status, and comorbidities were recorded. MEASUREMENTS AND RESULTS: Eight patients qualified. All had resolution of infection. The tube was removed after an average of 73.6 +/- 49.73 (95% confidence interval [CI]) days. The mean duration of antibiotic treatment was 5.37 +/- 1.04 (95% CI) weeks. None required surgery or experienced complications from an empyema tube. CONCLUSION: A strategy of empyema tube drainage with staged removal is an option in appropriately selected patients with chronic empyema, unexpandable lung, and poor surgical candidacy. PMID- 27185988 TI - Relationship of epidermal growth factor receptor activating mutations with histologic subtyping according to International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society 2011 adenocarcinoma classification and their impact on overall survival. AB - BACKGROUND: There is limited Indian data on epidermal growth factor receptor (EGFR) gene activating mutations (AMs) prevalence and their clinicopathologic associations. The current study aimed to assess the relationship between EGFR AM and histologic subtypes and their impact on overall survival (OS) in a North Indian cohort. PATIENTS AND METHODS: Retrospective analysis of nonsmall cell lung cancer patients who underwent EGFR mutation testing (n = 186) over 3 years period (2012-2014). EGFR mutations were tested using polymerase chain reaction amplification and direct sequencing. Patients were classified as EGFR AM, EGFR wild type (WT) or EGFR unknown (UKN). Histologically adenocarcinomas (ADC) were further categorized as per the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society-2011 classification. RESULTS: Overall EGFR AM prevalence was 16.6%. The ratio of exon 19 deletions to exon 21 L858R mutations was 3.17:1. Female sex (P = 0.002), never smoking status (P = 0.002), metastatic disease (P = 0.032), and nonsolid subtype of ADC (P = 0.001) were associated with EGFR AM on univariate logistic regression analysis (LRA). On multivariate LRA, solid ADC was negatively associated with EGFR AM. Median OS was higher in patients with EGFR AM (750 days) as compared to EGFR-WT (459 days) or EGFR-UKN (291 days) for the overall population and in patients with Stage IV disease (750 days vs. 278 days for EGFR-WT, P = 0.024). On univariate Cox proportional hazard (CPH) analysis, smoking, poor performance status (Eastern Cooperative Oncology Group >= 2), EGFR-UKN status, and solid ADC were associated with worse OS while female sex and lepidic ADC had better OS. On multivariate CPH analysis, lepidic ADC (hazard ratio [HR] =0.12) and EGFR-WT/EGFR UKN (HR = 2.39 and HR = 3.30 respectively) were independently associated with OS in separate analyses. CONCLUSIONS: Histologic subtyping of ADC performed on small biopsies is independently associated with EGFR AM and with better OS. EGFR AM presence is a positive prognostic factor for OS. PMID- 27185990 TI - A randomized, double-blind study comparing the efficacy and safety of a combination of formoterol and ciclesonide with ciclesonide alone in asthma subjects with moderate-to-severe airflow limitation. AB - CONTEXT: The combination of inhaled corticosteroids (ICS) and long-acting beta agonists (LABA) is widely used in the treatment of moderate-to-severe asthma uncontrolled by ICS alone. AIMS: To evaluate the efficacy and safety of a new ICS LABA combination inhaler containing Formoterol (F) and Ciclesonide (C). SETTINGS AND DESIGN: A double-blind, double-dummy, parallel group fashion, multi-centric study. SUBJECTS AND METHODS: A total of 169 asthma patients received Ciclesonide 80 MUg once daily during a 4-week run-in period, after which, they were randomized to receive either C (80 MUg) or a combination of F (4.5 MUg) and C (80 MUg) (FC) both delivered through a hydro-fluro-alkane pressurized-metered-dose inhaler as 1 puff twice daily, for 6 weeks. STATISTICAL ANALYSIS USED: Inter group differences were compared using t-test for independent samples at a significance level of 5%. RESULTS: From baseline, the improvements in forced expiratory volume in 1 s at 1, 3, and 6 weeks was significantly higher in the FC group compared to Group C (110 ml vs. 40 ml, 140 ml vs. 20 ml, and 110 ml vs. 40 ml, respectively, all P < 0.05). From baseline, the improvements in mean morning peak expiratory flow at 1, 3, and 6 weeks was significantly higher in the FC group compared to Group C (17 L/min vs.-3 L/min, 22 L/min vs. 3 L/min, and 30 ml vs. 8 L/min respectively, all P < 0.05). The changes in symptom scores were similar in both the groups. The adverse events in the FC group were not significantly different from those in the C group. CONCLUSIONS: FC provides better improvement than C alone in terms of lung function and symptoms without increased risk of adverse events in asthma patients. PMID- 27185991 TI - Clinical profile, etiology, and management of hydropneumothorax: An Indian experience. AB - INTRODUCTION: Hydropneumothorax is an abnormal presence of air and fluid in the pleural space. Even though the knowledge of hydro-pneumothorax dates back to the days of ancient Greece, not many national or international literatures are documented. AIM: To study clinical presentation, etiological diagnosis, and management of the patients of hydropneumothorax. MATERIALS AND METHODS: Patients admitted in a tertiary care hospital with diagnosis of hydropneumothorax between 2012 and 2014 were prospectively studied. Detailed history and clinical examination were recorded. Blood, pleural fluid, sputum investigations, and computed tomography (CT) thorax (if necessary) were done. Intercostal drainage (ICD) tube was inserted and patients were followed up till 3 months. RESULTS: Fifty-seven patients were studied. Breathlessness, anorexia, weight loss, and cough were the most common symptoms. Tachypnea was present in 68.4% patients. Mean PaO2 was 71.7 mm of Hg (standard deviation +/-12.4). Hypoxemia was present in 35 patients (61.4%). All patients had exudative effusion. Etiological diagnosis was possible in 35 patients by initial work-up and 22 required CT thorax for arriving at a diagnosis. Tuberculosis (TB) was etiology in 80.7% patients, acute bacterial infection in 14%, malignancy in 3.5%, and obstructive airway disease in 1.8%. All patients required ICD tube insertion. ICD was required for 24.8 days (+/-13.1). CONCLUSION: Most patients presented with symptoms and signs of cardiorespiratory distress along with cough, anorexia, and weight loss. Extensive pleural fluid analysis is essential in establishing etiological diagnosis. TB is the most common etiology. ICD for long duration with antimicrobial chemotherapy is the management. PMID- 27185992 TI - Comparison of oral montelukast with oral zileuton in acute asthma: A randomized, double-blind, placebo-controlled study. AB - BACKGROUND: Leukotriene modifiers have an established role in the management of chronic asthma but their role in acute asthma is still under evaluation. OBJECTIVE: To study and compare the effects of oral montelukast with oral zileuton in acute asthma. MATERIALS AND METHODS: This study included 120 asthmatics and was conducted from September 2012 to March 2014. Patients were randomized into three different groups to receive montelukast or zileuton or placebo in addition to standard treatment for asthma exacerbation. Peak expiratory flow rate (PEFR) values, details of rescue medication and vital signs were recorded at 6 h, 12 h, 24 h, and 48 h of drug or placebo administration and at discharge. Additional recording was done in the morning (8-10 am) following admission. The primary endpoint was the mean PEFR of each group at these time points; the secondary end point being the need for rescue medications. RESULTS: The mean PEFR recordings of the three study groups - placebo, montelukast, and zileuton - respectively, at various time points were as follows: at 6 h (223.25 +/- 90.40, 199.00 +/- 82.52, 233.75 +/- 84.05; P = 0.240); at 12 h (271.00 +/- 109.38, 251.50 +/- 101.44, 309.50 +/- 129.63; P = 0.048); at 24 h (288.25 +/- 114.26, 269.00 +/- 107.51, 324.50 +/- 127.88; P = 0.080); and at 48 h (295.00 +/- 114.80, 293.50 +/- 113.24, 344.75 +/- 119.91; P = 0.015); discharge (305.00 +/- 118.56, 305.25 +/- 119.51, 361.25 +/- 119.70; P = 0.010). The mean PEFR for the three study groups at 8-10 am on the morning following admission was 268.75 +/- 111.43, 252.50 +/- 99.99, 306.75 +/- 114.44; P = 0.047. Total rescue doses needed were 10, 1, and 0, respectively (P = 0.049). CONCLUSION: Zileuton is better than montelukast as an additional drug in acute asthma and results in significant improvement in lung function, and reduction in the need for rescue medications. PMID- 27185993 TI - Bronchoalveolar lavage cellular analyses in conjunction with high-resolution computed tomography imaging as a diagnostic intervention for patients with suspected interstitial lung disease. AB - BACKGROUND: Bronchoalveolar lavage (BAL) has gained acceptance for diagnosis of Interstitial lung disease (ILD). The advent of high-resolution computed tomography (HRCT) has reduced the clinical utility of BAL. This work has utilized the recommendations of the American Thoracic Society (ATS) to optimize BAL and the findings have been associated with clinical examination and HRCT to precisely narrow down the cause of ILD. MATERIALS AND METHODS: BAL was performed on ILD suspects at the target site chosen based on HRCT. The procedure, transport, processing, and analysis of BAL fluid were performed as per the ATS guidelines. The clinical data, HRCT findings and BAL report were used to narrow down the diagnosis of ILD. The statistical analysis was performed to assess the significance. RESULTS: The BAL procedure was optimized as per the recommendations of the ATS. In a cohort of 50 patients, Idiopathic pulmonary fibrosis, (8) hypersensitivity pneumonitis, (17) connective tissue disorder, (9) sarcoidosis, (3) pneumoconiosis, (5) acute respiratory distress syndrome, (2) eosinophilic lung disease (2) and lymphangitic carcinomatosa, (2) aspiration bronchiolitis (1) and pulmonary histiocytosis (1) were diagnosed. Statistically significant variation in differential counts was found in different ILDs. The different ILDs were classified based on the criteria described by the ATS. CLINICAL SIGNIFICANCE: BAL along with clinical and HRCT findings improved the diagnostic accuracy by incorporating, the acute or chronic nature of the disease and the cause for acute exacerbation, which helped in the better management of ILDs. PMID- 27185995 TI - Postcorrective surgery improvement of nocturnal hypoxemia in a case of partial anomalous pulmonary venous connection and aberrant hepatic vein drainage. AB - Partial anomalous pulmonary venous connection (PAPVC) is a rare congenital anomaly that leads to an anatomical left-to-right shunt. Termination of the intrahepatic inferior vena cava (IVC) with its azygos continuation associated with the hepatic venous connection to the left atrium (LA) is also a rare congenital anomaly that results in an anatomical right-to-left shunt. A 65-year old male presented with severe dyspnea on exertion and pedal edema. He was further diagnosed at our clinic and was found to have both the aforementioned congenital abnormalities, creating a bidirectional shunt. On further investigation, he was found to have nocturnal hypoxemia on overnight oximetry. The patient was successfully treated via surgical corrections of the congenital anomalies leading to symptomatic improvement as well as the resolution of nocturnal hypoxemia. PMID- 27185994 TI - Imaging of spaces of neck and mediastinum by endoscopic ultrasound. AB - Endoscopic ultrasound (EUS) of the mediastinum was pioneered by gastroenterologists, and it was taken up by pulmonologists when the smaller diameter endobronchial ultrasound (EBUS) scope was designed after a few years. The pulmonologists' approach remained largely confined to entry from the trachea, but they soon realized that the esophagus was an alternative route of entry by the EBUS scope. The new generations of interventionists are facing the challenge of learning two techniques (EUS and EBUS) from two routes (esophagus and trachea). The International Association for the Study of Lung Cancer (IASLC) proposed a classification of mediastinal lymph nodes at different stations that lie within the boundaries of specific spaces. These interventionists need clear definitions of landmarks and clear techniques to identify the spaces. There are enough descriptions of spaces of the neck and the mediastinum in the literature, yet the topic mentioned above has never been discussed separately. The anatomical structures, landmarks, and boundaries of spaces will be important to interventionists in the near future during performances of endosonography. This article combines the baseline anatomy of the spaces with the actual imaging during EUS. PMID- 27185996 TI - Whistle lower-better late than never. AB - 16 years old boy with childhood history of chronic respiratory symptoms requiring several admissions presented with recent worsening of symptoms. Chest x-ray showed left lower lobe collapse and flexible bronchoscopy revealed stenosis of left main bronchus. Foreign body was seen beyond the stenosis, which was removed after dilatation of narrowed bronchus under general anesthesia using rigid bronchoscopy. Patient's father gave a history of aspiration of whistle 14 years ago, which had then been removed. Patient is now free of symptoms after removal of foreign body. PMID- 27185997 TI - Osler-Weber-Rendu disease: A rare cause of recurrent hemoptysis. AB - Osler-Weber-Rendu disease, also known as hereditary hemorrhagic telangiectasia, is a rare autosomal dominant condition causing systemic fibrovascular dysplasia. It has an incidence of 1-2/100,000. Phenotypic variation is extreme ranging from asymptomatic to severely symptomatic, from cases with no or few mucocutaneous lesions to those with diffuse cutaneous telangiectasia. We discuss a case of Osler-Weber-Rendu disease causing diffuse cutaneous telangiectasia and hemoptysis. The patient presented with complaints of hemoptysis and was extensively examined and investigated before being diagnosed with Osler-Weber Rendu disease. We successfully managed the patient's hemoptysis by bronchial artery embolization. This case emphasizes the need for careful examination and investigation and to consider such rare diseases when all the common causes of hemoptysis are ruled out. An early and proper diagnosis will lead to more effective management of such a rare disease with few treatment options available. PMID- 27185998 TI - Congenital lobar emphysema: Pitfalls in diagnosis. AB - Congenital lobar emphysema (CLE) is a rare but life-threatening congenital anomaly leading to respiratory distress in early childhood. Diagnosis requires a strong clinical suspicion. We report a case of a 31/2-month-old infant who was initially diagnosed with pneumonia requiring multiple hospital admissions. After computed tomography of the thorax, a diagnosis on CLE was made. The child was planned for surgery in the next available routine operation theatre. However, suddenly in the evening, she developed respiratory distress and needed emergency surgical intervention. The child improved dramatically after surgery, and the postoperative period was uneventful. Early diagnosis and treatment in such cases can lead to dramatic results. PMID- 27185999 TI - Bronchocentric granulomatosis with extensive cystic lung disease in tuberculosis: An unusual presentation. AB - Tuberculosis is known to cause both cystic lung disease and bronchocentric granulomatosis (BCG). However, both are rare manifestations of this common disease. We report a case of BCG with extensive cystic lung disease in a young female who presented with fever, weight loss, and recurrent pneumothoraces with respiratory failure. Early diagnosis and treatment are imperative, as appropriate therapy may be life-saving in such cases. PMID- 27186000 TI - Delayed diagnosis of endobronchial mucoepidermoid carcinoma in a 29-year-old male. AB - Mucoepidermoid carcinoma (MEC) is an uncommon primary lung tumor. It usually involves large airways and presents clinically and radiologically with nonspecific features. Because of nonspecific presentation diagnosis is frequently delayed. We report the case of a 29-year-old male patient wherein a clinico radiological consideration of tuberculosis (TB) led to a prolonged treatment with anti-TB medications without response. Flexible bronchoscopic biopsy confirmed the diagnosis of MEC following that the patient underwent curative surgical resection. PMID- 27186001 TI - A case of synchronous isolated thyroid metastasis from a primary lung cancer presenting as thyroid primary: Diagnostic challenge! AB - The thyroid metastasis from any primary is rare, and usually is a late event and presents as a thyroid swelling. Further, the diagnosis of a metastatic lesion in a patient with no antecedent history of any malignancy can be very challenging. Recently, a patient presented to us with a history of diagnostic evaluation suggesting a primary thyroid malignancy with a synchronous lung primary. After surgery for the thyroid swelling, final histopathology revealed a metastatic lesion from a lung primary. Here, we discuss this rare case of isolated synchronous thyroid metastasis from a lung primary and review the relevant literature. PMID- 27186002 TI - Idiopathic bilateral diaphragmatic dysfunction as a cause of dyspnea. AB - Diaphragmatic paralysis is an unusual and often underrecognized cause of dyspnea. We present a case of bilateral diaphragmatic paralysis with no identifiable etiology. Our patient is a 73-year-old female with a history of smoking who presented with dyspnea and orthopnea. She was treated for obstructive lung disease with no improvement in dyspnea despite adequate therapy. She had pulmonary function tests (PFTs) that revealed marked decrease in vital capacity and was unable to perform lung volume maneuvers supine due to marked dyspnea. The maximal inspiratory pressure was 37 in the upright position and decreased to 27 in the supine position. She was given a presumptive diagnosis of idiopathic bilateral diaphragmatic dysfunction. Given the history, physical exam, and PFT findings, we felt that the patient did not need further invasive testing. The patient was treated with noninvasive mechanical ventilation due to hypercapnia and her symptoms improved. PMID- 27186003 TI - Is bronchoalveolar lavage a game changer in the diagnosis of interstitial lung disease? PMID- 27186005 TI - Is there a role of immunosenescence in the pathogenesis of malignant mesothelioma? A case study. PMID- 27186004 TI - "Crazy-paving" pattern: A characteristic presentation of pulmonary alveolar proteinosis and a review of the literature from India. PMID- 27186006 TI - Young onset hemoptysis: A rare cause of pulmonary arterial aneurysm. PMID- 27186007 TI - Scrub typhus presenting as pneumonia in a 12-year-old girl. PMID- 27186008 TI - A rare case of tubercular pansinusitis with orbital and intracranial extension. PMID- 27186009 TI - Latent tuberculosis. PMID- 27186010 TI - Response to transbronchial lung biopsy in diffuse parenchymal lung disease: Question still remains whether to go for surgical lung biopsy or not? PMID- 27186011 TI - Noninvasive ventilation outside Intensive Care Unit in India: Too many problems to counter. PMID- 27186012 TI - Metabolic activity of neutrophils is elevated in chronic obstructive pulmonary disease: Are we sure? PMID- 27186013 TI - Response to Metabolic activity of neutrophils is elevated in COPD. PMID- 27186014 TI - Not cysticercosis. PMID- 27186015 TI - Molecular characterization of CONSTANS-Like (COL) genes in banana (Musa acuminata L. AAA Group, cv. Grand Nain). AB - The CONSTANS (CO) family is an important regulator of flowering in photoperiod sensitive plants. But information regarding their role in day neutral plants is limited. We report identification of nine Group I type CONSTANS-like (COL) genes of banana and their characterization for their age dependent, diurnal and tissue specific expression. Our studies show that the Group I genes are conserved in structure to members in other plants. Expression of these genes shows a distinct circadian regulation with a peak during light period. Developmental stage specific expression reveals high level transcript accumulation of two genes, MaCOL3a and MaCOL3b, well before flowering and until the initiation of flowering. A decrease in their transcript levels after initiation of flowering is followed by an increase in transcription of other members that coincides with the continued development of the inflorescence and fruiting. CO binding cis-elements are observed in at least three FT -like genes in banana suggesting possible CO-FT interactions that might regulate flowering. Distinct tissue specific expression patterns are observed for different family members in mature leaves, apical inflorescence, bracts, fruit skin and fruit pulp suggesting possible roles other than flowering. This is the first exhaustive study of the COL genes belonging to Group I of banana. PMID- 27186016 TI - Evaluation of antimutagenic and protective effects of Parkinsonia aculeata L. leaves against H2O2 induced damage in pBR322 DNA. AB - The in vitro antimutagenic and DNA protecting potential of organic (methanol, hexane, n-butanol) and aqueous extract/fractions of Parkinsonia aculeata L. (Fabaceae) was investigated by employing Ames assay and DNA nicking assay. DNA damage by hydroxyl radicals was effectively inhibited by all the extract/fractions. A marked antimutagenic effect was observed against 4-Nitro-o phenylenediamine and sodium azide (direct acting mutagens) and 2-Aminofluorene (indirect acting mutagen) in TA98 and TA100 strains of Salmonella typhimurium. In Ames assay, two different modes of experiments i.e. pre-incubation and co incubation were performed and it was observed that all the extract/fractions showed better results in the pre-incubation as compared to co- incubation mode. Out of all the extract/fractions tested, n-butanol fraction was found to be the most effective in preventing DNA damage and inhibiting mutagenesis. UHPLC analysis of extract/fractions revealed presence of polyphenols such as gallic acid, catechin, chlorogenic acid, caffeic acid, umbelliferone, coumaric acid, rutin, and ellagic acid etc. DNA protecting and antimutagenic activity of this plant could be attributed to presence of these polyphenols. The results of this study indicate the presence of potent antioxidant factors in Parkinsonia aculeata L, which are being explored further for their mechanism of action. PMID- 27186017 TI - Genome- wide characterization of Nuclear Factor Y (NF-Y) gene family of sorghum [Sorghum bicolor (L.) Moench]: a bioinformatics approach. AB - Nuclear factor Y (NF-Y) is a heterotrimeric transcription factor (TF) complex with preferential binding to CCAAT elements of promoters, regulating gene expression in most of the higher eukaryotes. The availability of plant genome sequences have revealed multiple number of genes coding for the three subunits, namely NF-YA, NF-YB and NF-YC in contrast to single NF-Y gene for each subunit reported in yeast and animals. A total of 33 NF-YTF comprising of 8 NF-YA, 11 NF YB and 14 NF-YC subunits were accessed from the sorghum genome. The bioinformatic characterization of NF-Y gene family of sorghum for gene structure, chromosome location, protein motif, phylogeny, gene duplication and in-silico expression under abiotic stresses have been attempted in the present study. The identified SbNF-Y genes are distributed on all the 10 chromosomes of sorghum with variability in the frequency and 18 out of 33 SbNF-Ys were found to be intronless. Segmental duplication event was found to be predominant feature based on gene duplication pattern study. Several orthologs and paralogs groups were disclosed through the comprehensive phylogenetic analysis of SbNF-Y proteins along with 36 Arabidopsis and 28 rice NF-Y proteins. In-silico expression analysis under abiotic stresses using rice transcriptome data revealed several of the sorghum NF-Y genes to be associated with salt, drought, cold and heat stresses. PMID- 27186018 TI - Agrobacterium-mediated genetic transformation of commercially elite rice restorer line using nptII gene as a plant selection marker. AB - Transformation of commercially important indica cultivars remains challenging for the scientific community even though Agrobacterium-mediated transformation protocols for a few indica rice lines have been well established. We report successful transformation of a commercially important restorer line JK1044R of indica rice hybrid JKRH 401. While following existing protocol, we optimized several parameters for callusing, regeneration and genetic transformation of JK1044R. Calli generated from the rice scutellum tissue were used for transformation by Agrobacterium harboring pCAMBIA2201. A novel two tire selection scheme comprising of Geneticin (G418) and Paramomycin were deployed for selection of transgenic calli as well as regenerated plantlets that expressed neomycin phosphotransferase-II gene encoded by the vector. One specific combination of G418 (30 mg l(-1)) and Paramomycin (70 mg l(-1)) was very effective for calli selection. Transformed and selected calli were detected by monitoring the expression of the reporter gene uidA (GUS). Regenerated plantlets were confirmed through PCR analysis of nptII and gus genes specific primers as well as dot blot using gus gene specific as probe. PMID- 27186019 TI - Biolistic transformation of Scoparia dulcis L. AB - Here, we report for the first time, the optimized conditions for microprojectile bombardment-mediated genetic transformation in Vassourinha (Scoparia dulcis L.), a Plantaginaceae medicinal plant species. Transformation was achieved by bombardment of axenic leaf segments with Binary vector pBI121 harbouring beta glucuronidase gene (GUS) as a reporter and neomycin phosphotransferase II gene (npt II) as a selectable marker. The influence of physical parameters viz., acceleration pressure, flight distance, gap width & macroprojectile travel distance of particle gun on frequency of transient GUS and stable (survival of putative transformants) expressions have been investigated. Biolistic delivery of the pBI121 yielded the best (80.0 %) transient expression of GUS gene bombarded at a flight distance of 6 cm and rupture disc pressure/acceleration pressure of 650 psi. Highest stable expression of 52.0 % was noticed in putative transformants on RMBI-K medium. Integration of GUS and npt II genes in the nuclear genome was confirmed through primer specific PCR. DNA blot analysis showed more than one transgene copy in the transformed plantlet genomes. The present study may be used for metabolic engineering and production of biopharmaceuticals by transplastomic technology in this valuable medicinal plant. PMID- 27186020 TI - Expression of an endochitinase gene from Trichoderma virens confers enhanced tolerance to Alternaria blight in transgenic Brassica juncea (L.) czern and coss lines. AB - An endochitinase gene 'ech42' from the biocontrol fungus 'Trichoderma virens' was introduced to Brassica juncea (L). Czern and Coss via Agrobaterium tumefaciens mediated genetic transformation method. Integration and expression of the 'ech42' gene in transgenic lines were confirmed by PCR, RT-PCR and Southern hybridization. Transgenic lines (T1) showed expected 3:1 Mendelian segregation ratio when segregation analysis for inheritance of transgene 'hpt' was carried out. Fluorimetric analysis of transgenic lines (T0 and T1) showed 7 fold higher endochitinase activity than the non-transformed plant. Fluorimetric zymogram showed presence of endochitinase (42 kDa) in crude protein extract of transgenic lines. In detached leaf bioassay with fungi Alternaria brassicae and Alternaria brassicicola, transgenic lines (T0 and T1) showed delayed onset of lesions as well as 30-73 % reduction in infected leaf area compared to non-transformed plant. PMID- 27186021 TI - DUF538 protein superfamily is predicted to be chlorophyll hydrolyzing enzymes in plants. AB - The possible hydrolytic activity towards chlorophyll molecules was predicted for DUF538 protein superfamily in plants. It was examined by using computational as well as experimental tools including in vitro chlorophyll degradation, antioxidant compounds production and in vivo real-time gene expression tests. Comparison of the computational data with the experimental results indicated that DUF538 proteins might be chlorophyll hydrolyzing enzyme (most probably carboxyesterase) which degrade chlorophyll molecules (66 % per 12 hrs) to produce new compounds (1.8 fold per 12 hrs) with antioxidant properties. The relevance of DUF538 gene expression level with the chlorophyll contents (2.8 fold increase per chlorophyll content of 50 %) of the drought-stressed leaves showed that chlorophyll degradation by DUF538 is most probably induced in response to stress stimuli. Despite membranous chlorophyll catabolic pathways, DUF538-dependent reactions is predicted to be occurred in the cytosol of the under stressed plants. We addressed as to whether chlorophyll breakdown to antioxidant compounds by DUF538 is a defense mechanism of plants against stress stimuli, in vivo? This question is going to be investigated in our next research project. PMID- 27186022 TI - Genetic variation assessment of acid lime accessions collected from south of Iran using SSR and ISSR molecular markers. AB - Iran has a long history of acid lime cultivation and propagation. In this study, genetic variation in 28 acid lime accessions from five regions of south of Iran, and their relatedness with other 19 citrus cultivars were analyzed using Simple Sequence Repeat (SSR) and Inter-Simple Sequence Repeat (ISSR) molecular markers. Nine primers for SSR and nine ISSR primers were used for allele scoring. In total, 49 SSR and 131 ISSR polymorphic alleles were detected. Cluster analysis of SSR and ISSR data showed that most of the acid lime accessions (19 genotypes) have hybrid origin and genetically distance with nucellar of Mexican lime (9 genotypes). As nucellar of Mexican lime are susceptible to phytoplasma, these acid lime genotypes can be used to evaluate their tolerance against biotic constricts like lime "witches' broom disease". PMID- 27186023 TI - Evaluation of genetic diversity amongst Descurainia sophia L. genotypes by inter simple sequence repeat (ISSR) marker. AB - Descurainia sophia is a valuable medicinal plant in family of Brassicaceae. To determine the range of diversity amongst D. sophia in Iran, 32 naturally distributed plants belonging to six natural populations of the Iranian plateau were investigated by inter-simple sequence repeat (ISSR) markers. The average percentage of polymorphism produced by 12 ISSR primers was 86 %. The PIC values for primers ranged from 0.22 to 0.40 and Rp values ranged between 6.5 and 19.9. The relative genetic diversity of the populations was not high (Gst =0.32). However, the value of gene flow revealed by the ISSR marker was high (Nm = 1.03). UPGMA clustering method based on Jaccard similarity coefficient grouped the genotypes into two major clusters. Graph results from Neighbor-Net Network generated after a 1000 bootstrap test using Jaccard coefficient, and STRUCTURE analysis confirmed the UPGMA clustering. The first three PCAs represented 57.31 % of the total variation. The high levels of genetic diversity were observed within populations, which is useful in breeding and conservation programs. ISSR is found to be an eligible marker to study genetic diversity of D. sophia. PMID- 27186024 TI - Assessment of genetic diversity of Saltol QTL among the rice (Oryza sativa L.) genotypes. AB - Eight Saltol quantitative trait locus (QTL) linked simple sequence repeat (SSR) markers of rice (Oryza sativa L.) were used to study the polymorphism of this QTL in 142 diverse rice genotypes that comprised salt tolerant as well as sensitive genotypes. The SSR profiles of the eight markers generated 99 alleles including 20rare alleles and 16 null alleles. RM8094 showed the highest number (13) of alleles followed by RM3412 (12), RM562 (11), RM493 (9) and RM1287 (8) while as, RM10764 and RM10745 showed the lowest number (6) of alleles. Based on the highest number of alleles and PIC value (0.991), we identified RM8094 as suitable marker for discerning salt tolerant genotypes from the sensitive ones. Based upon the haplotype analysis using FL478 as a reference (salt tolerant genotypes containing Saltol QTL), we short listed 68 rice genotypes that may have at least one allele of FL478 haplotype. Further study may confirm that some of these genotypes might have Saltol QTL and can be used as alternative donors in salt tolerant rice breeding programmes. PMID- 27186025 TI - Polymorphism analysis in advanced mutant population of oat (Avena sativa L.) using ISSR markers. AB - Present investigation was carried out to evaluate genetic diversity among 38 M6 population of oat cv. JO-1. To validate the observed morpho-physiological variations, these lines were analyzed with 21 ISSR primers. A total of 132 loci were amplified by these 21 ISSR markers and 116 loci were found to be polymorphic (87.87 %). The genetic similarity coefficient values among 39 oat genotypes based on ISSR analysis ranged from 0.305 to 0.957. The cluster analysis divided the oat genotypes into two groups. Mutants JMO 81 and JMO 82 were found to be most divergent, hence can be used as parents in breeding program for the development of superior cultivars. PMID- 27186026 TI - In vitro evaluation of excess copper affecting seedlings and their biochemical characteristics in Carthamus tinctorius L. (variety PBNS-12). AB - The present study was focused to recognize the changes in the Safflower (Carthamus tinctorius L. variety PBNS-12), when exposed to different concentration of copper (25, 50 and 100 MUM) along with control (0.5 MUM) for 10 and 20 days. This experiment used Hoagland's nutrient solution to meet the external nutrient conditions, which includes micro and macronutrients equivalent to soil solution with copper sulphate (CuSO4. 5H2O) as a metal stress. The plant samples were harvested after 10 and 20 days. The effect of increased concentrations of copper was indicated by the reduction in overall growth with reduced fresh and dry weight. Copper stress caused significant increase in the non- enzymatic antioxidants (polyphenols and flavonoids) in leaves of treated safflower seedlings as compared to the control. Also, enhanced accumulation of proline was observed in the safflower leaves. In response to excess copper concentration, the level of MDA content was found to be increased. The results showed that the copper has time and dose-dependent effects on safflower seedlings. PMID- 27186027 TI - In vitro propagation, micromorphological studies and ex vitro rooting of cannon ball tree (Couroupita guianensis aubl.): a multipurpose threatened species. AB - In vitro propagation methods using seeds and nodal segments of a 21-year old Couroupita guianensis - a medicinally important but threatened tree have been developed. Hundred percent of the seeds germinated on half strength Murashige and Skoog (MS) medium with 2.0 mg l(-1) indole-3 butyric acid (IBA). Nodal segments were found most suitable for the establishment of cultures. About 90 % explants responded and 4.1 +/- 0.23 shoots per node were induced after five weeks of inoculation on MS medium +4.0 mg l(-1) 6-benzylaminopurine (BAP). Further shoot multiplication was achieved by repeated transfer of mother explants and subculturing of in vitro produced shoots on fresh medium. Maximum number (8.2 +/- 0.17) of shoots were regenerated on MS medium with 1.0 mg l(-1) each of BAP and Kinetin (Kin) + 0.5 mg l(-1) alpha-naphthalene acetic acid (NAA) with additives (50 mg l(-1) of ascorbic acid and 25 mg l(-1) each of adenine sulphate, L arginine and citric acid). The multiplied shoots rooted (4.3 +/- 0.26 roots/shoot) on half strength MS medium with 2.5 mg l(-1) IBA. All the shoots were rooted ex vitro when pulse treated with 400 mg l(-1) of IBA for five min with an average of 7.3 +/- 0.23 roots per shoot. Nearly 86 % of these plantlets were acclimatized within 7-8 weeks and successfully transferred in the field. Biologically significant developmental changes were observed during acclimation particularly in leaf micromorphology in terms of changes in stomata, veins and vein-islets, and trichomes. This study helps in understanding the response by the plants towards outer environmental conditions during acclimatization. This is the first report on micropropagation of C. guianensis, which could be used for the large-scale multiplication, restoration and conservation of germplasm of this threatened and medicinally important tree. PMID- 27186028 TI - Mass propagation of Plectranthus bourneae Gamble through indirect organogenesis from leaf and internode explants. AB - The present study describes the plant propagation via indirect organogenesis from in vitro derived leaf and internode explants of Plectranthus bourneae, an endemic plant to south India. Leaf and internodal explants successfully callused on Murashige and Skoog medium (MS) supplemented with different concentrations of auxins [2,4-D (2,4-dichlorophenoxyacetic acid), NAA (alpha-naphthalene acetic acid), IAA (indole-3 acetic acid), IBA (indole-3-butyric acid) and PIC (Picloram); 0.1-2.0 mg/l] in combination with BA (6-benzyladenine) (0.5 mg/l). Maximum callus induction (98 %) was achieved from leaf explant followed by internodal explant (89 %) at 1.0 mg/l NAA, 0.5 mg/l BA. Leaf derived callus showed better shoot regeneration (29.71 shoots) on MS medium containing 1.0 mg/l KN (kinetin), 0.7 mg/l NAA, and 50 mg/l CH (casein hydrolysate) followed by internodal callus (19.71). A maximum of 19.14 roots/shoot was observed at 1.0 mg/l IBA. The rooted plantlets were successfully hardened and transferred to greenhouse condition with 80 % survival. This system could be utilized for large scale multiplication of P. bourneae by tissue culture. PMID- 27186029 TI - Determining the most effective traits to improve saffron (Crocus sativus L.) yield. AB - To determine the effective traits to improve saffron yield, a split plot design based on RBCD was done in Mashhad region in Iran for three years (2012-2014). The results showed that all traits except number of daughter corm, fresh weight of daughter corm and dry leaf weight had low general heritability. Results of genotypic and phenotypic coefficients of variation and genetic advance demonstrated that the majority of traits had a low diversity and the selection did not have any effect in improving the traits. As a result, the best way to increase saffron yield is improvement of farm management. It was also found that saffron yield had the highest phenotypic and genotypic correlations with fresh and dry weight of daughter corm and dry and fresh flower weight. Therefore, the efforts to improve these traits will increase saffron yield. According to the present study 5-Jun to 5-Jul was found to be the best sowing date for planting saffron. Also, the Mashhad and Torbat ecotypes were the best ecotypes in this study. Phenotypic and genotypic path analysis showed that in the first step three traits number of daughter corm, fresh flower weight and flower number and in the second step traits fresh weight of daughter corm, dry flower weight and dry leaf weight interred to the regression model and had the highest positive direct and indirect effects on saffron yield. Mainly, it can be derived that the implementation of correct farm management including appropriate sowing date, saffron ecotypes, proper density, bigger and higher quality saffron corm can play an important role in improving yield components and subsequently increasing saffron yield. PMID- 27186030 TI - Computational approaches for classification and prediction of P-type ATPase substrate specificity in Arabidopsis. AB - As an extended gamut of integral membrane (extrinsic) proteins, and based on their transporting specificities, P-type ATPases include five subfamilies in Arabidopsis, inter alia, P4ATPases (phospholipid-transporting ATPase), P3AATPases (plasma membrane H(+) pumps), P2A and P2BATPases (Ca(2+) pumps) and P1B ATPases (heavy metal pumps). Although, many different computational methods have been developed to predict substrate specificity of unknown proteins, further investigation needs to improve the efficiency and performance of the predicators. In this study, various attribute weighting and supervised clustering algorithms were employed to identify the main amino acid composition attributes, which can influence the substrate specificity of ATPase pumps, classify protein pumps and predict the substrate specificity of uncharacterized ATPase pumps. The results of this study indicate that both non-reduced coefficients pertaining to absorption and Cys extinction within 280 nm, the frequencies of hydrogen, Ala, Val, carbon, hydrophilic residues, the counts of Val, Asn, Ser, Arg, Phe, Tyr, hydrophilic residues, Phe-Phe, Ala-Ile, Phe-Leu, Val-Ala and length are specified as the most important amino acid attributes through applying the whole attribute weighting models. Here, learning algorithms engineered in a predictive machine (Naive Bays) is proposed to foresee the Q9LVV1 and O22180 substrate specificities (P-type ATPase like proteins) with 100 % prediction confidence. For the first time, our analysis demonstrated promising application of bioinformatics algorithms in classifying ATPases pumps. Moreover, we suggest the predictive systems that can assist towards the prediction of the substrate specificity of any new ATPase pumps with the maximum possible prediction confidence. PMID- 27186031 TI - Profiling expression of lipoxygenase in cucumber during compatible and incompatible plant-pathogen interactions. AB - We compared lipoxygenase (LOX) expression in cucumber in response to host and non host pathogens. Our results displayed significant difference in expression of LOX between compatible and incompatible interaction at 12, 24 and 48 h after inoculation. Moreover, LOX expression at 72 h after inoculation was similar in both compatible and incompatible interaction. It seems that early induction of LOX plays a crucial role in plant defense against pathogens. PMID- 27186032 TI - Challenges in the Surgical Treatment of Retroperitoneal Sarcomas. AB - The objective of this study is to assess long-term prognosis and patterns of failure in patients with retroperitoneal sarcoma who underwent surgery with curative intent at a single institution. We also provide a thorough review of the literature including several series and widely variable data regarding local and distant failure. During a 25-year period (1988-2013), 45 consecutive patients who underwent surgery for retroperitoneal sarcoma at a single referral center were reviewed retrospectively. We recorded and analyzed the presenting symptoms, type of surgical excision, and the 5-year survival rate as well as the local recurrence rate of patients with complete tumor resection. Overall survival is significantly diminished in patients in whom resection margins are not adequate. In our series, 5-year recurrence rate for patients with complete and incomplete resection of the tumor was 30.76 and 68.42 %, respectively. The 5-year survival rate was 51.12 %, and the 5-year survival rate according to type of resection was 76.93 % for complete and 15.79 % for incomplete resections. Local recurrence after first surgery and high-grade malignancy are associated with poor survival. The role of radiation therapy and chemotherapy in the treatment of retroperitoneal sarcoma (RPS) should be investigated further. Complete en bloc resection of the tumor mass and adjacent structures is the single most important factor that improves survival. PMID- 27186033 TI - Literature Analysis of the Treatment of Benign Esophageal Disease with Stent. AB - To analyze the efficacy and safety of benign esophageal disease used biodegradable (BD) stent or metal stent. The English literatures of benign esophageal disease that were treated by biodegradable or metal stents implantation were retrieved and summarized. In all 323 benign esophageal disease, the most common etiologies were benign refractory stricture, surgical anastomotic stricture and esophageal fistula/leak/perforation, but the main characteristics between the two groups were not significantly different. One hundred fifty-four cases were completely healed by using BD stents or self-expandable metal stents (SEMS) (47.7 %). Clinical success was achieved in 47.7 % of all patients and there was no significant difference between BD stents (51 %) and SEMS (46.2 %) (P = 0.472), while stent migration occurred more frequently with SEMS (33.9 %) than with BD stent (19.6 %) (P <= 0.05), and tissue in- or overgrowth occurred more frequently with SEMS (22.2 %) than with BD stents (8.8 %) (P <= 0.05). Furthermore, the time about degradation of BD stents in esophageal was longer than removal of SEMS from the esophagus (P <= 0.05). Placement of BD stents or SEMS provides effective and safe relief for benign esophageal disease. Clinical success and mortality were not significantly different. BD stents offers an advantage of fewer complications. Although stent placement is a viable strategy in patients with benign esophageal disease, the ideal treatment strategy and further randomized trials with large number of patients are needed. PMID- 27186034 TI - Heme Oxygenase-1 Promoter Polymorphism Protects Liver Allograft. AB - Heme oxygenase-1 has been identified to protect allograft from ischemia/reperfusion and immunologic rejection. Activity of heme oxygenase-1 is regulated by a guanine-thymine dinucleotide length polymorphism in the heme oxygenase-1 gene promoter. In this study, we aimed to explore the impact of the heme oxygenase-1 gene promoter polymorphism of donors and recipients on the orthotopic liver graft function after transplantation. Sixty recipients and their accompanying donors of orthotopic liver allografts were included retrospectively in this study. Heme oxygenase-1 gene promoter polymorphism was assessed using genomic DNA isolated from cryopreserved splenocytes or peripheral blood mononuclear cells and analyzed by genetic analyzer. Small allele of the donor heme oxygenase-1 gene polymorphism significantly prolonged the graft survival (p = 0.017). Recipients of allografts from a class of small-allele carrier had significantly lower serum total bilirubin compared with recipients of a nonclass small-allele donor liver (p < 0.01). Additionally, in recipients of small-carrier allografts, cold ischemia time (<10 h or >=10 h) did not affect the total bilirubin significantly. Our study suggested a protective function of donor derived heme oxygenase-1 gene promoter polymorphism on orthotopic liver allograft function after transplantation. PMID- 27186035 TI - Evaluation of Factors Affecting the Type of Gallstone. AB - The aim of this study is to determine the factors affecting the formation of the gallstone types of cholesterol and pigment stones. This descriptive and retrospective study comprised 164 patients who underwent cholecystectomy. Research data were obtained using a data collection form with 34 questions developed by the researchers based on the relevant literature. Statistical analysis of the data was made on SPSS 15.0 software using the percentage assessment method and chi-square test. Advanced statistical analysis of the data was performed using multivariate logistic regression. Cholesterol stone was found to form in individuals with anemia, those going through the menopause, and those consuming liquid oil and not undertaking exercise. The risk of pigment stone formation was found to be higher in the obese and those with liver disease and who do not consume milk. From the results of the study, it was determined that the dietary habits, chronic diseases, and lifestyle behaviors of individuals could be effective factors in the formation of cholesterol and/or pigment stone. PMID- 27186036 TI - Rational Hyperoxia in the Perioperative Period: a Safe and Effective Tool in the Reduction of SSI. AB - Oxygen supplemented at a concentration higher than 40-50 % for at least 2 h perioperatively is expected to reduce surgical site infections (SSI). Although supplementation of 80 % of oxygen perioperatively has shown to reduce SSI in various studies, this concentration is known to be associated with airway complications. This study was taken up to assess the efficacy of 60 %, i.e. <80 and >50 %, inspired oxygen supplemented perioperatively in reducing SSI. One hundred and eighty-eight patients who underwent elective class I and II surgeries were studied. Patients were divided equally into two groups and subgroups and matched for age, sex, type of surgeries, etc. The control group received 30 % and the study group received 60 % oxygen supplementation perioperatively for 2 h. Wounds were observed for the development of SSI. 8/94 patients in the study group and 13/94 patients in the control group developed SSI (p < 0.01). The results indicate a relative risk of 1.62, risk difference of 0.0531 and attributable risk of 38.42 %. Hence, it may be concluded that perioperative oxygen supplementation at 60 % concentration reduces SSI. PMID- 27186037 TI - A Review on the History of 'Thyroid Surgery'. AB - The history of thyroid surgery is both interesting and illustrative. The ambitions of a thyroid surgeon have evolved along the length of time. The objective of this article is to give an idea about the evolution of thyroid surgery thus giving inspiration to future surgeons in their quest for a perfect technique, which would take into consideration disease elimination and maintenance of physiology and cosmesis. The history of thyroid surgery back to as early as 952 AD, when Albucasis first performed the surgery. Thereafter, the course of this surgery had its crests and troughs. At one point of time, surgeons refused to perform this surgery because of the complications. But later on, surgeons like Billroth and Kocher gave this procedure a new leash of life, after which this surgery became popular and underwent numerous modifications to where now it stands. History reveals that thyroid surgery has travelled a long path in time. From an operation which once was considered dreadful to the present times when techniques are being tried to make the incision as small as possible. The quest is still on to develop the perfect technique. PMID- 27186038 TI - Circumcaval Ureter-the Paradigm Shift in Diagnosis and Management. AB - An anomalous development of infra-renal inferior vena cava leads to circumcaval ureter or preureteral vena cava, a rare congenital anomaly with an autopsy incidence of 0.9 per 1000. We present a case of circumcaval ureter and review the literature with a special emphasis on the paradigm shift seen during the last decade, in diagnostic and management strategies. PMID- 27186041 TI - Mass in the Left Iliac Fossa-a Diagnostic Dilemma. AB - Clinical diagnosis of abdominal masses remains a challenge to this day; in spite of the availability of advanced imaging facilities, we fail to reach a definitive diagnosis in a few cases and have to resort to a laparotomy, which reveals unexpected findings. We present a case of a 70-year-old lady who presented with pain abdomen and loss of appetite for 3 months; clinical examination revealed a fixed intra-abdominal firm to hard mass in the left iliac fossa. CT scan of the abdomen showed a large cystic hypodense lesion in the left iliac, lumbar and hypogastric region with no definite organ of origin. The patient underwent an exploratory laparotomy and in toto excision of the cyst; on opening the cyst wall, we found multiple daughter cysts in a pool of thick, purulent fluid. Microscopic examination confirmed the presence of a hydatid cyst Primary peritoneal hydatid cysts are a rare entity and constitute around 2 % of hydatid cysts found in the human body. Very few cases of primary peritoneal hydatid cyst have been reported from non-endemic areas, and this case report highlights the need to maintain a high index of suspicion while evaluating cystic abdominal swellings. PMID- 27186039 TI - Hurthle Cell Lesion: Controversies, Challenges, and Debates. AB - Hurthle cell lesion is one of the most questionable clinico-pathological entities in most of its aspects. Literature has used the terms oncocytic, oxyphilic, Hurthle, and Ashkanazy interchangeably; what does each term denote? Who first described these cells? What is the cell of origin? How much Hurthle cells should be present to define the lesion as Hurthle cell one? Is it possible to differentiate hyperplastic from neoplastic and benign from malignant Hurthle cell lesion on a non-histopathologic ground? Does it belong to follicular or to papillary neoplasms or should it be classified separately? Can we anticipate its clinical behavior or predict its outcome? How can we manage? We will try to answer these questions in light of the ongoing relevant arguments with the aim of resolving some uncertainties and suggesting how to solve others. PMID- 27186040 TI - Extraosseous Ewing Sarcoma: Diagnosis, Prognosis and Optimal Management. AB - Extraosseous Ewing sarcomas (EESs) are rare tumours originating from soft tissues. Their clinical picture depends mainly on the primary site of the sarcoma. Patient characteristics and outcomes seem to be different in EES compared to patients with skeletal Ewing sarcoma, with implications for patient care and prognosis. However, multimodality therapeutic strategies are recommended for all types of the Ewing tumour family. The available diagnostic tools include ultrasonographic evaluation and computed tomography (CT) or magnetic resonance imaging as well as histopathologic and immunohistochemical tissue examination. Several histologic and genetic biomarkers have been established, although their utilization needs to be further tested by larger prospective studies. Regarding localized disease, the recommended treatment remains surgery. However, chemotherapy can be added to achieve improved survival, with neoadjuvant regimens showing more promising results than adjuvant regimens. Radiotherapy is an option to obtain local control, although its complications have reduced its utilization. In metastatic or recurrent disease, systematic chemotherapy improves survival. PMID- 27186042 TI - Laparoscopic Management of Hilar Cholangiocarcinoma: a Case Report. AB - The only option for cure of Klatskin's tumour is surgical excision. The radicality of the procedure is determined by the extent of the tumour and functional parameters of the patient. Complete laparoscopic resection of hilar cholangiocarcinoma with biliary reconstruction is a challenging procedure. The main aim is to achieve pathological negative margins, complete lymph node retrieval and enterobiliary bypass. We present a case report of a patient with hilar cholangiocarcinoma managed laparoscopically. The nodal yield was nine. On 6 month follow-up, the patient was symptom free. The main aim is to study the feasibility of performing this complex procedure completely laparoscopically. PMID- 27186043 TI - Rapid Remission of Psoriasis After Sleeve Gastrectomy. AB - Psoriasis is a multifactorial, inflammatory chronic skin condition affecting 1-3 % of the population worldwide. Obesity is more common in patients with psoriasis. Psoriasis and obesity are linked via a mechanism of chronic inflammation. There are reports on improvement of psoriasis after obesity surgery. Role of sleeve gastrectomy in psoriasis improvement is not fully elucidated yet. In this article, we describe two obese patients with psoriasis who had improvement of their skin lesions 1 month after sleeve gastrectomy. To our knowledge, this is the first report of psoriasis remission after sleeve gastrectomy in current medical literature. PMID- 27186045 TI - Primary Malignant Melanoma of Vagina Treated by Total Pelvic Exenteration. AB - Primary malignant melanoma of vagina is a rare variant of melanoma and usually associated with a grave prognosis. Radical surgery is the only treatment option with reasonable loco regional control. A case of primary malignant melanoma involving whole of vagina infiltrating urethra and reaching up to vulva was treated by surgery and postoperative radiotherapy. The tumor was infiltrating bladder and rectum reaching the anal sphincter. Total pelvic exenteration was done to achieve tumor-free surgical margins. One year after treatment, patient is disease free. PMID- 27186044 TI - Duplication of Vermiform Appendix. AB - The vermiform appendix is a tubular, narrow, worm-shaped part of the alimentary canal that lies near the ileocecal junction and communicates with the caecum. Duplication of the vermiform appendix is rare, with a reported incidence of 0.004 %. Till now, fewer than 100 cases have been reported. We present a case of an 8 year-old male child with duplex appendix who presented to the emergency department of our institution with features of acute appendicitis. PMID- 27186046 TI - Giant Vesical Calculus Formation as a Complication of Augmentation Cystoplasty. AB - A 44-year-old female presented with the history of recurrent UTI and intermittent hematuria. She underwent augmentation ileocystoplasty for small capacity bladder 19 years back. Patient was on clean intermittent catheterization (CIC) since then. Abdominal radiograph and ultrasonography showed the large vesical calculus. Open cystolithotomy was done, and a yellowish brown hard stone weighing 1025 g was removed. Chemical analysis revealed struvite stone. Postoperative period was uneventful. Regular bladder wash, lifelong surveillance and follow-up is advisable. PMID- 27186047 TI - Culinary Medicine-Jalebi Adhesions. AB - Culinary terms have been used to describe anatomy (bean-shaped kidneys), pathology (strawberry gall bladder), clinical signs (cafe-au-lait spots), radiological images (sausage-shaped pancreas), etc. While Indian cuisine is popular all over the world, no Indian dish finds mention in medical terminology. In intra-abdominal adhesions, sometimes, the intestinal loops are so densely adherent that it is difficult to make out proximal from distal and it is impossible to separate them without injuring the bowel resulting in spill of contents-resection is the only option (Fig. 1). Jalebi, an Indian dessert, has a single long tubular strip of fried batter filled with sugary syrup so intertwined that it is impossible to discern its ends; if broken, the syrup spills out-the best way to relish it is to chew the whole piece (Fig. 2). Because of these similarities between them, I propose to name dense intra-abdominal adhesions as 'jalebi adhesions.' PMID- 27186048 TI - Telementoring: an Overview and Our Preliminary Experience in the Setting Up of a Cost-effective Telementoring Facility. AB - Telementoring as a subset of telemedicine has evolved over the past few years, but it is yet to be utilized to its full potential. The technology holds promise in bridging divides of distance and enables far-flung areas to be mentored in operative advances. It thus has a special bearing in countries like India where health care is short staffed and many areas lack availability of quality care. We describe the setting up of a telementoring facility at our centre. As against a 'routine' facility with dedicated equipments which cost heavily, our facility was set up using mostly equipments commonly available in an operating room. The facility is presently functional and allows telementoring through an encrypted Web-based service. Our set-up design can be emulated in centres with financial constraint and can help raise the standard of surgical care. PMID- 27186049 TI - Sleeve Right Lower Lobectomy: a Rarely Performed Extended Resection. AB - Sleeve resection is a valid option in the surgical treatment of lung tumors, avoiding large resection. To ensure a good functional result and avoid post operative complications like recent broncho-pleural fistulas and long-term stenosis, anastomosis between bronchi must be well performed. We report two cases of sleeve resection of the right lower lobe and show how we managed caliber discrepancy between the middle lobe bronchus and the truncus intermedius. PMID- 27186050 TI - The Legacy of Yasargil: the Father of Modern Neurosurgery. PMID- 27186051 TI - The "Pygmalion Effect" and Surgical Mentoring. PMID- 27186052 TI - Local and Oral Antibiotics with Avoidance of Constipation (LOABAC) Treatment for Anal Fissure: a New Concept in Conservative Management. PMID- 27186053 TI - Longitudinal Pancreatico-Jejunostomy Vs lateral Pancreatico-Gastrostomy as a Drainage Procedure for Pain Relieve in Chronic Pancreatitis Done in a Tertiary Referral Centre of Eastern India. PMID- 27186055 TI - Under-Utilization of Implantable Cardioverter Defibrillators in Patients with Heart Failure - The Current State of Sudden Cardiac Death Prophylaxis. AB - BACKGROUND: Despite ACC/AHA guidelines indicating implantable cardioverter defibrillator (ICD) as class I therapy for primary prevention of sudden cardiac death in patients with EF<=35%, ICD utilization rates in real world practice have been low. OBJECTIVE: To determine the rate of ICD implantation at a tertiary care academic center and to assess the reasons for under-utilization of the same. METHODS: Review of a prospectively collected database which included all patients diagnosed with an EF<=35% was performed to assess the rate of ICD implantation and mortality. Reasons for non-implantation of ICD were then assessed from detailed chart review. RESULTS: A total of 707 patients (age 69.4 +/- 14.1 years) with mean EF of 26+/-7% were analyzed. Only 28% (200/707) of patients had ICDs implanted. Mortality was lower in the group with ICD (25% vs 37%, p=0.004). When patients who either died or were lost to follow-up prior to 2005 were excluded, ICD utilization rate was still low at 37.6%. The most common reason for non implantation of ICD was physicians not discussing this option with their patients. Patient refusal was the second most common reason. CONCLUSIONS: ICD Implantation rates for primary prevention of SCD in patients with EF<=35% is low. Physician and patient education should be addressed to improve the utilization rates. PMID- 27186056 TI - Arthroplasty of the shoulder joint. PMID- 27186057 TI - Accuracy of patient-specific instrumentation in anatomic and reverse total shoulder arthroplasty. AB - PURPOSE: Glenoid component malposition is associated with poor function and early failure of both anatomic and reverse total shoulder arthroplasty. Glenoid positioning is challenging particularly in the setting of bone loss or deformity. Recently, the use of computer assistance has been shown to reduce implantation error. The aim of this study is to evaluate the accuracy of patient-specific instrumentation in cases of anatomic and reverse shoulder replacement in vivo. METHODS: Twenty patients underwent total shoulder arthroplasty using a computed tomography (CT)-based patient-specific instrumentation (PSI) system, ten anatomic and ten reverse. Preoperative three-dimensional digital templating of glenoid component position was undertaken and surgery then performed using a custom-made guide. Postoperative CT scans were used to compare final implanted component position to the preoperatively planned position in the same patient. RESULTS: Final component position and orientation closely reflected the preoperatively templated position. Mean deviation in the glenoid version from planned was 1.8 degrees +/-1.9 degrees (range, 0.1 degrees -7.3 degrees ). Mean deviation in inclination was 1.3 degrees +/-1.0 degrees (range, 0.2 degrees -4.5 degrees ). Mean deviation in position on the glenoid face was 0.5 +/- 0.3 mm (range, 0.0-1.3 mm) in the anteroposterior plane and 0.8 +/- 0.5 mm (range, 0.0-1.9 mm) in the superoinferior plane. Actual achieved version was within 7 degrees of neutral in all cases except for one where it was deliberately planned to be outside of this range. CONCLUSION: PSI in both anatomic and reverse shoulder arthroplasty is highly accurate in guiding glenoid component implantation in vivo. The system can reliably correct bony deformity. PMID- 27186058 TI - Observation of initial postoperative radiolucent lines using a modern pegged glenoid design. AB - PURPOSE: Glenoid component loosening remains a common mode of failure for total shoulder arthroplasty and has inspired improvements in implant design, instrumentation, and surgical technique. The purpose of this manuscript was to evaluate the incidence of radiolucent lines and glenoid seating on initial postoperative radiographs using a modern pegged-glenoid design, instrumentation, and surgical technique. MATERIALS AND METHODS: We performed a retrospective analysis of a consecutive series of 100 pegged-glenoid total shoulder replacements. In cases of excessive glenoid version, the glenoid was asymmetrically reamed to recreate more normal version. Initial postoperative radiographs were evaluated for the presence of radiolucent lines and completeness of glenoid seating. The preoperative glenoid version measured on axial computed tomography (CT) scans was used to compare differences in version among those with complete and incompletely seated glenoids. RESULTS: The rate of radiolucent lines observed on postoperative radiographs was 0%. Complete glenoid seating (Grade A) was observed in 81 patients (observer 1) and 82 patients (observer 2). Measurements of preoperative CT scans found a higher percentage of abnormal glenoid version for incompletely seated glenoids (47%) than completely seated glenoids (34%) but no significant difference (P = 0.327). The mean preoperative glenoid retroversion for incompletely seated glenoids was 12.1 degrees and 9.1 degrees for completely seated glenoids (P = 0.263). CONCLUSIONS: Modern surgical techniques, surgical instrumentation, and peg glenoid design have facilitated the ability to eliminate radiolucent lines on initial postoperative radiographs with high rates of complete seating of glenoid components. Incomplete seating may be related to incomplete correction of glenoid version. PMID- 27186054 TI - Intensive Care in India: The Indian Intensive Care Case Mix and Practice Patterns Study. AB - AIMS: To obtain information on organizational aspects, case mix and practices in Indian Intensive Care Units (ICUs). PATIENTS AND METHODS: An observational, 4-day point prevalence study was performed between 2010 and 2011 in 4209 patients from 124 ICUs. ICU and patient characteristics, and interventions were recorded for 24 h of the study day, and outcomes till 30 days after the study day. Data were analyzed for 4038 adult patients from 120 ICUs. RESULTS: On the study day, mean age, Acute Physiology and Chronic Health Evaluation (APACHE II) and sequential organ failure assessment (SOFA) scores were 54.1 +/- 17.1 years, 17.4 +/- 9.2 and 3.8 +/- 3.6, respectively. About 46.4% patients had >=1 organ failure. Nearly, 37% and 22.2% patients received mechanical ventilation (MV) and vasopressors or inotropes, respectively. Nearly, 12.2% patients developed an infection in the ICU. About 28.3% patients had severe sepsis or septic shock (SvSpSS) during their ICU stay. About 60.7% patients without infection received antibiotics. There were 546 deaths and 183 terminal discharges (TDs) from ICU (including left against medical advice or discharged on request), with ICU mortality 729/4038 (18.1%). In 1627 patients admitted within 24 h of the study day, the standardized mortality ratio was 0.67. The APACHE II and SOFA scores, public hospital ICUs, medical ICUs, inadequately equipped ICUs, medical admission, self-paying patient, presence of SvSpSS, acute respiratory failure or cancer, need for a fluid bolus, and MV were independent predictors of mortality. CONCLUSIONS: The high proportion of TDs and the association of public hospitals, self-paying patients, and inadequately equipped hospitals with mortality has important implications for critical care in India. PMID- 27186059 TI - Blood transfusion after total shoulder arthroplasty: Which patients are at high risk? AB - PURPOSE: There are multiple reported risk factors and a wide range of reported blood transfusion rates for total shoulder arthroplasty (TSA). There are no evidence-based guidelines for blood transfusions in TSA patients. MATERIALS AND METHODS: We utilized the Nationwide Inpatient Sample to analyze 51,191 patients undergoing TSA between 1998 and 2011. The purpose was to describe the incidence and identify the preoperative factors that are independently associated with blood transfusion after TSA. In addition, we studied the association of blood transfusions with certain variables such as length of stay (LOS), total charges, and payer status. RESULTS: The blood transfusion rate in our study was 6.1%. There was no difference in the rate of blood transfusions over the study period (P < 0.001). In our logistic regression model, significant associations were found with increased age (odds ratio [OR] =1.03), white race (OR = 1.05), higher Charlson-Deyo score (OR = 1.12), presence of ischemic heart disease (OR = 1.24), blood loss anemia (OR = 1.65), female gender (OR = 1.94), presence of coagulation disorders (OR = 2.25), and presence of deficiency anemia (OR = 3.5). Patients receiving a blood transfusion had higher total charges, a longer hospital LOS, and were more likely to be Medicare payers (P < 0.001). CONCLUSIONS: Our study found five clinically significant risk factors for blood transfusions for TSA: female gender, ischemic heart disease, deficiency anemia, coagulation disorder, and blood loss anemia. Patients with these risk factors should be considered higher risk for requiring a blood transfusion after TSA and counseled appropriately. LEVEL OF EVIDENCE: Level II, retrospective cohort study, prognostic study. PMID- 27186061 TI - Reconstruction of the elbow and forearm for Ewing sarcoma of ulna: A new biological technique. AB - Primary bone tumors around the elbow represent <1% of all the skeletal tumors. Surgery with or without adjuvant therapy (radiotherapy, chemotherapy) is the treatment of choice for malignant tumors. Reconstruction of the elbow and forearm in malignant tumors is challenging as it involves a complex interplay between multiple joints which need to be stabilized for the optimal functional outcome. We describe a new technique for the reconstruction of the elbow after resection of a proximal ulna tumor with articular radio-ulnar synostosis with the creation of a single bone forearm. We attempted to achieve a mobile elbow and stable wrist joint with the radio-ulnar union at the proximal articular surface of the ulna resulting in a single bone forearm. The procedure involves an oblique osteotomy preserving the olecranon process (after taking adequate margins based on oncological principles) and its articular cartilage along with the attachment of the triceps tendon. Then the radial head was partially denuded of its cartilage using a burr, leaving cartilage only on the volar side, and then fused to the remnant olecranon. Osteosynthesis was done using compression screw and tension band wiring. The advantages of this procedure are that the mobility at wrist and elbow are retained, it requires minimal hardware and allows for primary closure of the wound. PMID- 27186060 TI - Rotator cuff tears after total shoulder arthroplasty in primary osteoarthritis: A systematic review. AB - Rotator cuff tears have been reported to be uncommon following total shoulder arthroplasty (TSA). Postoperative rotator cuff tears can lead to pain, proximal humeral migration, and glenoid component loosening. The purpose of this paper was to evaluate the incidence of post-TSA rotator cuff tears or dysfunction in osteoarthritic patients. A systematic review of multiple databases was performed using preferred reporting items for systematic reviews and meta-analyses guidelines. Levels I-IV evidence clinical studies of patients with primary osteoarthritis with a minimum 2-year follow-up were included. Fifteen studies with 1259 patients (1338 shoulders) were selected. Student's t-tests were used with a significant alpha value of 0.05. All patients demonstrated significant improvements in motion and validated clinical outcome scores (P < 0.001). Radiographic humeral head migration was the most commonly reported data point for extrapolation of rotator cuff integrity. After 6.6 +/- 3.1 years, 29.9 +/- 20.7% of shoulders demonstrated superior humeral head migration and 17.9 +/- 14.3% migrated a distance more than 25% of the head. This was associated with an 11.3 +/- 7.9% incidence of postoperative superior cuff tears. The incidence of radiographic anterior humeral head migration was 11.9 +/- 15.9%, corresponding to a 3.0 +/- 13.6% rate of subscapularis tears. We found an overall 1.2 +/- 4.5% rate of reoperation for cuff injury. Nearly all studies reported indirect markers of rotator cuff dysfunction, such as radiographic humeral head migration and clinical exam findings. This systematic review suggests that rotator cuff dysfunction following TSA may be more common than previously reported. IV, systematic review of Levels I-IV studies. PMID- 27186063 TI - Case report of bisphosphonate-associated atypical scapular fracture and brief literature review. PMID- 27186062 TI - Osteochondritis dissecans on the medial aspect of the humeral head. AB - The case of a 29-year-old man who had osteochondritis dissecans on the medial aspect of the humeral head is reported. Repetitive micro-trauma at a low elevated arm position was thought to have induced the osteochondral lesion. PMID- 27186064 TI - African-American and Latino Parents' Attitudes and Beliefs Regarding Adolescent Fighting and Its Prevention. AB - Adolescent fighting affects 25% of youth, with the highest rates among African Americans and Latinos but little is known about parental views on youth fighting. The purpose of this study was to examine African-American and Latino parents' perspectives on adolescent fighting and methods to prevent fighting. We conducted four focus groups with parents of African-American and Latino urban adolescents. Focus groups were stratified by race/ethnicity and fighting status. Groups were audiotaped, transcribed, and analyzed by three independent coders using thematic content analysis. Seventy-six percent of the 17 participants were female. Latino parents condoned fighting only as a last resort, and taught children about consequences of fighting, emotional regulation, and non-violent conflict resolution strategies. African-American parents endorsed teaching non-violent strategies, but expressed some doubts about their effectiveness. African-American parents also suggested corporal punishment, but acknowledged that this may not be an optimal long-term strategy. Positive role modeling and involvement by teachers and other adults were cited as having important roles in fighting prevention. Suggested interventions included teaching adolescents non-violent conflict resolution skills, anger management, and alternatives to fighting. Parents recommended that violence prevention programs incorporate the experiences of former fighters and be tailored to community needs. Study findings suggest that youth violence-prevention programs may benefit from addressing parental attitudes towards fighting and parent-child communication about fighting, teaching adolescents non-violent conflict-resolution skills, and tailoring programs by race/ethnicity. Promoting positive modeling and involvement by teachers and other adults also may be beneficial. PMID- 27186065 TI - Large-Vessel Sealing in Laparoscopic Colectomy with an Ultrasonic Device. AB - BACKGROUND AND OBJECTIVE: The Harmonic ACE+7 Shears with Advanced Hemostasis Mode (Ethicon, Somerville, NJ, USA) is an ultrasonic device designed to transect and seal vessels up to 7 mm in diameter. The device applies an algorithm that optimizes ultrasonic energy delivery combined with a longer sealing cycle. The purpose of this study was to assess the initial clinical experience with the Harmonic device by evaluating large-vessel sealing during laparoscopic colectomy in consecutive cases. METHODS: This prospective, multicenter, observational series involved 40 adult patients who were to undergo elective laparoscopic colectomy where dissection and transection of the inferior mesenteric artery was indicated. The primary study endpoint was first-pass hemostasis, defined as a single activation of the Advanced Hemostasis Mode to transect and seal the inferior mesenteric artery. The use of any additional energy device or hemostatic product to establish or maintain hemostasis was noted. Patients were observed after surgery for ~4 weeks for adverse events that were considered to be related to the study procedure or study device. Descriptive statistical analyses were performed for study endpoints. RESULTS: Forty patients underwent the laparoscopic colectomy procedure. First-pass hemostasis of the inferior mesenteric artery was achieved and maintained in all 40 patients, with no required additional hemostatic measures. Exposure of the vessel was reported as skeletonized in 22 of 40 (55%) patients. Mean transection time was 21.9 +/- 7.4 s. One adverse event (postoperative anemia) was considered possibly related to the study device. CONCLUSION: In this initial clinical consecutive series, the device demonstrated successful transection and sealing of the large mesenteric vessels during laparoscopic colorectal surgery. PMID- 27186066 TI - Hiatal Hernia Repair with Novel Biological Graft Reinforcement. AB - BACKGROUND AND OBJECTIVES: Hiatal hernias are repaired laparoscopically with increasing use of reinforcement material. Both synthetic and biologically derived materials reduce the recurrence rate compared to primary crural repair. Synthetic mesh introduces complications, such as mesh erosion, fibrosis, and infection. Urinary bladder matrix (UBM) represents a biologically derived material for use in hiatal hernia repair reinforcement with the potential to improve durability of repair without incurring the risks of other reinforcement materials. METHODS: The 15 cases presented involved hiatal hernia repair with primary crural repair with UBM reinforcement and fundoplication. Patients were followed for an average of 3 years, and were assessed with upper gastrointestinal (GI) series, endoscopy, and assessments of subjective symptoms of gastroesophageal reflux disease (GERD). RESULTS: Hernia diameters averaged 6 cm. Each repair was successful and completed laparoscopically. UBM exhibited favorable handling characteristics when placed as a horseshoe-type graft sutured to the crura. One patient underwent endoscopic balloon dilatation of a mild postoperative stenosis that resolved. No other complications occurred. In more than 3 years of follow-up, there have been no recurrences or long-term complications. GERD-health-related quality of life (HRQL) scores averaged 6 (range, 0-12, of a possible 50), indicating little reflux symptomatology. Follow-up upper GI series were obtained in 9 cases and showed intact repairs. An upper endoscopy was performed in 8 patients and showed no recurrences. CONCLUSION: Surgeons may safely use laparoscopic fundoplication with UBM reinforcement for successful repair of hiatal hernias. In this series, repairs with UBM grafts have been durable at 3 years of follow-up and may serve as an alternative to synthetic mesh reinforcement of hiatal hernia repairs. PMID- 27186067 TI - Retroperitoneal Approach in Single-Port Laparoscopic Hysterectomy. AB - BACKGROUND AND OBJECTIVES: In single-port laparoscopic hysterectomy(SP-LH), ligation of the uterine artery is a fundamental step. We analyzed the effectiveness and safety of 2 different surgical approaches to ligate the uterine artery in SP-LH for women with uterine myomas or adenomyosis. METHODS: A single surgeon (TJ Kim) performed 36 retroperitoneal single-port laparoscopic hysterectomies (SP-rH) from September 1st 2012 to April 30th 2013. We compared these cases with 36 cases of conventional single-port laparoscopic abdominal hysterectomy (SP-aH) performed by the same surgeon from November 1st 2011 to July 31th 2012 (historic control). In the SP-rH cases, the retroperitoneal space was developed to identify the uterine artery; then, it was ligated where it originates from the internal iliac artery. RESULTS: Estimated blood loss (EBL) was decreased in the SP-rH group compared with the SP-aH group (100 mL vs 200 mL; P = .023). The median total operative time was shorter in the SP-rH group (75 minutes vs 93 minutes; P < .05). The operative time of the Scope I phase, including ligation of the utero-ovarian (or infundibulopelvic) ligament, round ligament, uterine artery, and detachment of the bladder, was longer in the SP-rH group compared with that in the SP-aH group (26.0 minutes vs 24 minutes; P = .043). However, the operative time of the Scope II phase, including detachment of the uterosacral-cardinal ligament, vaginal cutting, and uterus removal, was shorter in the SP-rH group (19.5 minutes vs 30 minutes; P < .05). Operative complications were not significantly different between the groups (P = .374). CONCLUSION: Although SP-rH may be considered technically difficult, it can be performed safely and efficiently with surgical outcomes comparable to those of SP aH. PMID- 27186068 TI - Transanal Total Mesorectal Excision With Single-Incision Laparoscopy for Rectal Cancer. AB - BACKGROUND AND OBJECTIVES: There has been great enthusiasm for the technique of transanal total mesorectal excision. Coupled with this procedure, we performed single-incision laparoscopic surgery for left colon mobilization. This is a description of our initial experience with the combined approach. METHODS: Patients with distal or mid rectal cancer were included. The operation was performed by 2 teams: one team performed the single-incision mobilization of the left colon via the right lower quadrant ileostomy site, and the other team performed the total mesorectal excision with a transanal platform. RESULTS: During the study period, 10 patients (5 men) with cancer of the rectum underwent the surgery. The mean age was 62.2 +/- 11.1 years, and the mean body mass index was 23.4 +/- 3.2 kg/m(2). The tumor's mean distance from the anal verge was 5.1 +/- 2.5 cm. The median operating time was 247.5 minutes (range, 188-462 minutes). The mean estimated blood loss was 124 +/- 126 mL (range, 10-188 mL). Conversion to multiport laparoscopy was needed in one case (10%). Postoperative pain, as reflected by the pain score, was minimal. The mean number of lymph nodes harvested was 15.6 +/- 3.8. All specimens had clear distal and circumferential radial margins. The overall complication rate was 10%. CONCLUSION: Our experience showed transanal total mesorectal excision with single-incision laparoscopy to be a feasible option for rectal cancer. Patients reported minimal postoperative pain. Further studies on the long-term outcome are warranted. PMID- 27186069 TI - Laparoscopic Extracorporeal Appendectomy in Overweight and Obese Children. AB - BACKGROUND AND OBJECTIVES: To compare surgical outcomes of overweight and obese patients with acute appendicitis who have undergone single-port extracorporeal laparoscopically assisted appendectomy (SP) with those who have had conventional 3-port laparoscopic appendectomy (TP). METHODS: This single-center retrospective chart review included patients 21 years of age and younger with a preoperative diagnosis of appendicitis who underwent laparoscopic appendectomy from January 2010 through December 2015. Cases of gangrenous and perforated appendicitis were excluded. Subgroup analyses of patients with acute appendicitis were performed. Operative time (OT), length of stay (LOS), and cost were compared between groups stratified by body mass index (BMI) and operative technique. RESULTS: A total of 625 appendectomies were performed-457 for acute appendicitis. Sixty-eight patients were overweight. The SP technique (n = 30) had shorter OT (median minutes, 41 vs 68; P < .001), lower cost (median , $5741 vs $8530; P < .001), and shorter LOS (median hours, 16 vs 19; P = .045) than the TP technique had (n = 38). Seventy patients were obese: 19 were treated with SP and 51 with TP. LOS did not differ significantly between the SP and TP groups, but subjects treated with SP had shorter OT (median minutes, 39 vs 63; P < .001) and lower cost (median, $6401 vs $8205; P = .043). CONCLUSIONS: The SP technique for acute appendicitis was found to have a significantly shorter OT and lower cost in all weight groups. There were minimal differences in LOS. SP should be considered in patients with acute appendicitis, regardless of their weight. PMID- 27186071 TI - Evaluation of treatment for dry eye with 2-hydroxyestradiol using a dry eye rat model. AB - PURPOSE: 2-hydroxy estradiol (2-OHE2) is a catechol derivative of 17beta Estradiol (E2) and it is synthesized from E2 catalyzed by cytochrome P4501A1. Previous studies reported that 2-OHE2 is a physiologic antioxidant in lipoproteins, liver microsomes, and the brain. Catechol derivatives show an anti inflammatory effect through the inhibition of prostaglandin endoperoxide synthase (PGS) activity. Corneal erosion caused by dry eye is related to an increase in oxidative stress and inflammation in ocular surface cells. We investigated the therapeutic effects of 2-OHE2 on corneal damage caused by dry eye. METHODS: Steroidal radical scavenging activity was confirmed through the electron spin resonance (ESR) method. PGS activity was measured using the COX Fluorescent Activity Assay Kit. To evaluate the effect of 2-OHE2 on the treatment for dry eye, 2-OHE2 was applied as an eye drop experiment using dry eye model rats. RESULTS: 2-OHE2 scavenged tyrosyl radical and possibly suppressed oxidative stress in corneal epithelial cells. In addition, 2-OHE2 inhibited PGS activity, and 2-OHE2 is probably a competitive inhibitor of PGS. Corneal PGS activity was upregulated in the dry eye group. Therefore, 2-OHE2 eye drops improved corneal erosion in dry eye model rats. CONCLUSIONS: 2-OHE2 is a candidate for the treatment of dry eye through the suppression of inflammation and oxidative stress in the cornea. PMID- 27186072 TI - Long-term outcomes in chronic obstructive pulmonary disease patients: exploring the effects of inhalatory devices and their influence on the outcome. AB - PURPOSE: Numerous systematic reviews have examined the outcomes in patients with chronic obstructive pulmonary disease managed with different therapeutic strategies. However, no such studies have specifically focused on the effect of inhalation devices. METHODS: A standard PubMed search was carried out in which we identified all randomized placebo-controlled trials conducted in patients with moderate-to-severe or severe chronic obstructive pulmonary disease. The clinical end points were exacerbations rate, incidence of pneumonia, and mortality. Meta regression was employed to assess the effect of the device. For the incidence of exacerbations, an equivalence analysis was also carried out. RESULTS: A total of 37 studies were analyzed. Four different devices were used across these trials (Respimat((r)), HandiHaler((r)), Diskus, and Turbuhaler((r))). Our meta regression analysis failed to show any significant difference between devices with regard to exacerbation rate. Equivalence was shown for some comparisons (HandiHaler((r)) vs Respimat((r))), but not for others. In analyzing mortality, Respimat((r)) was shown to worsen this end point in comparison with Turbuhaler((r)) and HandiHaler((r)). Moreover, Turbuhaler((r)) showed a protective effect over Diskus in the incidence of pneumonia. CONCLUSION: The results of our analysis represent the first attempt to explore the effect of the type of device on long-term outcomes. One important limitation was that most drugs were associated with one particular device, and so the effects of drugs and devices could not be reliably differentiated from one another. PMID- 27186070 TI - Tenascin-C promotes angiogenesis in fibrovascular membranes in eyes with proliferative diabetic retinopathy. AB - PURPOSE: We previously demonstrated that tenascin-C was highly expressed in the fibrovascular membranes (FVMs) of patients with proliferative diabetic retinopathy (PDR). However, its role in the pathogenesis of FVMs has not been determined. The purpose of this study was to investigate what role tenascin-C plays in the formation and angiogenesis of FVMs. METHODS: The level of tenascin-C was determined by sandwich enzyme-linked immunosorbent assay in the vitreous samples collected from patients with PDR and with a macular hole as control. The locations of tenascin-C, alpha- smooth muscle actin (SMA), CD34, glial fibrillary acidic protein (GFAP), and integrin alphaV in the FVMs from PDR patients were determined by immunohistochemistry. We also measured the in vitro expression of the mRNA and protein of tenascin-C in vascular smooth muscle cells (VSMCs) stimulated by interleukin (IL)-13. The effects of tenascin-C on cell proliferation, migration, and tube formation were determined in human retinal endothelial cells (HRECs) in culture. RESULTS: The mean vitreous levels of tenascin-C were significantly higher in patients with PDR than in patients with a macular hole (p<0.001). Double immunofluorescence analyses of FVMs from PDR patients showed that tenascin-C co-stained FVMs with alpha-SMA, CD34, and integrin alphaV but not with GFAP. In addition, IL-13 treatment increased both the expression and secretion of tenascin-C by VSMCs in a dose-dependent manner. Tenascin-C exposure promoted proliferation, migration, and tube formation in HRECs. Tenascin-C neutralizing antibody significantly blocked the tube formation by HRECs exposed to VSMC-IL-13-conditioned medium. CONCLUSIONS: Our findings suggest that tenascin-C is secreted from VSMCs and promotes angiogenesis in the FVMs associated with PDR. PMID- 27186073 TI - Patient considerations in the use of transdermal iontophoretic fentanyl for acute postoperative pain. AB - Opioids are commonly used in the management of moderate-to-severe postoperative pain. Patient-controlled analgesic techniques are recognized as preferred administration methods. Previously, research has focused on intravenously administered opioids via a programmable pump. More recently, an iontophoretic transdermal system (ITS), which is patient controlled, has been developed. The focus of this review is on pain management using the fentanyl ITS during the 24 72-hour time period immediately following surgery. Fentanyl ITS offers a needle free alternative to traditional intravenous (IV) patient-controlled analgesia (PCA) system that is as effective and safe as IV PCA. This system is easy to use for both patients and nurses. The use of fentanyl ITS is generally associated with a better ease-of-care profile, including a greater ease of mobility, from a patients' perspective when compared with morphine IV PCA. PMID- 27186075 TI - Retrospective analysis of quality improvement when using liposome bupivacaine for postoperative pain control. AB - BACKGROUND/OBJECTIVE: Liposome bupivacaine, a prolonged-release bupivacaine formulation, recently became available at the Naval Medical Center San Diego (NMCSD); before availability, postsurgical pain for large thoracic/abdominal procedures was primarily managed with opioids with/without continuous thoracic epidural (CTE) anesthesia. This retrospective chart review was part of a clinical quality initiative to determine whether postsurgical outcomes improved after liposome bupivacaine became available. METHODS: Data from patients who underwent laparotomy, sternotomy, or thoracotomy at NMCSD from May 2013 to May 2014 (after liposome bupivacaine treatment became available) were compared with data from patients who underwent these same procedures from December 2011 to May 2012 (before liposome bupivacaine treatment became available). Collected data included demographics, postoperative pain control methods, opioid consumption, perioperative pain scores, and lengths of intensive care unit and overall hospital stays. RESULTS: Data from 182 patients were collected: 88 pre-liposome bupivacaine (laparotomy, n=52; sternotomy, n=26; and thoracotomy, n=10) and 94 post-liposome bupivacaine (laparotomy, n=49; sternotomy, n=31; and thoracotomy, n=14) records. Mean hospital stay was 7.0 vs 5.8 days (P=0.009) in the pre- and post-liposome bupivacaine groups, respectively, and mean highest reported postoperative pain score was 7.1 vs 6.2 (P=0.007), respectively. No other significant between-group differences were observed for the overall population. In the laparotomy subgroup, there was a reduction in the proportion of patients who received CTE anesthesia post-liposome bupivacaine (22% [11/49] vs 35% [18/52] pre-liposome bupivacaine). CONCLUSION: Surgeons and anesthesiologists have changed the way they manage postoperative pain since the time point that liposome bupivacaine was introduced at NMCSD. Our findings suggest that utilization of liposome bupivacaine may be a useful alternative to epidural anesthesia. PMID- 27186074 TI - Idiopathic intracranial hypertension, hormones, and 11beta-hydroxysteroid dehydrogenases. AB - Idiopathic intracranial hypertension (IIH) results in raised intracranial pressure (ICP) leading to papilledema, visual dysfunction, and headaches. Obese females of reproductive age are predominantly affected, but the underlying pathological mechanisms behind IIH remain unknown. This review provides an overview of pathogenic factors that could result in IIH with particular focus on hormones and the impact of obesity, including its role in neuroendocrine signaling and driving inflammation. Despite occurring almost exclusively in obese women, there have been a few studies evaluating the mechanisms by which hormones and adipokines exert their effects on ICP regulation in IIH. Research involving 11beta-hydroxysteroid dehydrogenase type 1, a modulator of glucocorticoids, suggests a potential role in IIH. Improved understanding of the complex interplay between adipose signaling factors such as adipokines, steroid hormones, and ICP regulation may be key to the understanding and future management of IIH. PMID- 27186077 TI - Cardiac dysfunction among soft tissue sarcoma patients in Denmark. AB - PURPOSE: Soft tissue sarcoma (STS) patients may experience post-treatment cardiotoxicity, yet no population-based data exist. We examined the incidence of left ventricular ejection fraction (LVEF) decline, heart failure, and cardiac death following STS diagnosis among adults, using Danish patient registries and medical record review. PATIENTS AND METHODS: LVEF decline was examined in a regional cohort of STS patients diagnosed during 1997-2011 in Western Denmark for whom cardiac imaging data were available. LVEF decline was defined as an absolute decline from baseline to follow-up of 10% or more, or, where baseline imaging was not available, a decline below the lower limit of normal (or 40%) for a follow-up LVEF. Heart failure and cardiac death were investigated in a national Danish cohort of all STS patients diagnosed from 2000 to 2009. We followed patients from STS diagnosis until heart failure, cardiac death, emigration or December 31, 2012 (whichever occurred first). RESULTS: The incidence rate of LVEF decline for the regional cohort with follow-up data (N=100, five events) or baseline and follow up measurements (N=75, 19 events) was 16.8 (95% confidence interval [CI]: 7.0 40.3) and 108 (95% CI: 69-170), respectively, per 1,000 person-years. In the national cohort (N=1,187), the incidence of heart failure (40 events) and cardiac death (15 events) was 7.3 (95% CI: 5.4-10.0) and 2.7 (95% CI: 1.6-4.5), respectively, per 1,000 person-years. The strongest predictors of heart failure were doxorubicin treatment (hazard ratio [HR] =2.2, 95% CI: 0.5-10.2) and pre existing cardiovascular disease (HR=6.3, 95% CI: 0.98-40.6). CONCLUSION: LVEF decline occurred more frequently compared to heart failure or cardiac death in a nationally representative cohort of Danish STS patients. PMID- 27186076 TI - Modulation of breast cancer cell viability by a cannabinoid receptor 2 agonist, JWH-015, is calcium dependent. AB - INTRODUCTION: Cannabinoid compounds, both nonspecific as well as agonists selective for either cannabinoid receptor 1 (CB1) or cannabinoid receptor 2 (CB2), have been shown to modulate the tumor microenvironment by inducing apoptosis in tumor cells in several model systems. The mechanism of this modulation remains only partially delineated, and activity induced via the CB1 and CB2 receptors may be distinct despite significant sequence homology and structural similarity of ligands. METHODS: The CB2-selective agonist JWH-015 was used to investigate mechanisms downstream of CB2 activation in mouse and human breast cancer cell lines in vitro and in a murine mammary tumor model. RESULTS: JWH-015 treatment significantly reduced primary tumor burden and metastasis of luciferase-tagged murine mammary carcinoma 4T1 cells in immunocompetent mice in vivo. Furthermore, JWH-015 reduced the viability of murine 4T1 and human MCF7 mammary carcinoma cells in vitro by inducing apoptosis. JWH-015-mediated reduction of breast cancer cell viability was not dependent on Galphai signaling in vitro or modified by classical pharmacological blockade of CB1, GPR55, TRPV1, or TRPA1 receptors. JWH-015 effects were calcium dependent and induced changes in MAPK/ERK signaling. CONCLUSION: The results of this work characterize the actions of a CB2-selective agonist on breast cancer cells in a syngeneic murine model representing how a clinical presentation of cancer progression and metastasis may be significantly modulated by a G-protein-coupled receptor. PMID- 27186078 TI - Incidence of anemia in patients diagnosed with solid tumors receiving chemotherapy, 2010-2013. AB - PURPOSE: The purpose of this study was to evaluate and characterize the risk of anemia during the course of chemotherapy among patients with five common types of solid tumors. PATIENTS AND METHODS: Patients diagnosed with incident cancers of breast, lung, colon/rectum, stomach, and ovary who received chemotherapy were identified from Kaiser Permanente Southern California Health Plan (2010-2012). All clinical data were collected from the health plan's electronic medical records. Incidence proportions of patients developing anemia and 95% confidence intervals were calculated overall and by anemia severity and type, as well as by stage at cancer diagnosis, and by chemotherapy regimen and cycle. RESULTS: A total of 4,426 patients who received chemotherapy were included. Across cancers, 3,962 (89.5%) patients developed anemia during the course of chemotherapy (normocytic 85%, macrocytic 10%, microcytic 5%; normochromic 47%, hyperchromic 44%, hypochromic 9%). The anemia grades were distributed as follows: 58% were grade 1, 34% grade 2, 8% grade 3, and <1% grade 4. The incidence of grade 2+ anemia ranged from 26.3% in colorectal cancer patients to 59.2% in ovarian cancer patients. Incidence of grade 2+ anemia increased from 29% in stage I to 49% in stage IV. Incidence of grade 2+ anemia varied from 18.2% in breast cancer patients treated with cyclophosphamide + docetaxel regimen to 59.7% in patients with ovarian cancer receiving carboplatin + paclitaxel regimen. CONCLUSION: The incidence of moderate-to-severe anemia (hemoglobin <10 g/dL) remained considerably high in patients with solid tumors receiving chemotherapy. The risk of anemia was greater in patients with distant metastasis. PMID- 27186080 TI - Profile of olaparib in the treatment of advanced ovarian cancer. AB - Olaparib is a poly(ADP-ribose) polymerase inhibitor that received accelerated approval from the US Food and Drug Administration as monotherapy for patients with germline BRCA mutations and ovarian cancer treated with three or more prior lines of chemotherapy. This article summarizes the mechanism of poly(ADP-ribose) polymerase inhibition, therapeutic profile and uses of olaparib, and current and ongoing literature pertaining to olaparib in advanced ovarian cancer. PMID- 27186079 TI - Exploring the versatility of gingiva-colored composite. AB - Gingival recession has a diverse etiology. The consequences may include gingivitis, periodontitis, and hypersensitivity. Whereas the management can include surgical treatment options, sometimes a more conservative, yet still esthetic approach may be required. The use of gingiva-colored composites provides one such alternative and can be applied to varying presentations of the problem. While surgical treatment can be successful in re-creating favorable esthetic anatomy as well as achieving accurate tissue contour in cases when minor amounts of tissue are reconstructed, long-term results vary because of the vascularity and complexity of the interdental space. Factors such as cost, healing time, discomfort, and variable long-term results make surgery an unpopular choice. If tooth-colored restorative materials are utilized to restore cervical tooth exposure as a result of severe recession, the disproportionate appearance of the visible crown may give a dissatisfying result. Gingiva-colored composite provides dental practitioners with a versatile material that can be used to directly restore cervical defects caused by gingival recession, thus correcting the appearance of the gingival anatomy. It offers a treatment option that may increase patient satisfaction through the provision of a cost-effective, minimally invasive solution with highly esthetic results. PMID- 27186081 TI - Progressive symmetric vertical macular wide angioid streak-like lacquer crack. AB - PURPOSE: We report an unusual case of bilateral vertical lacquer crack with no history of ocular trauma and with progressive marked enlargement and consequent visual loss. METHODS: Three-year follow-up was completed using best-corrected visual acuity, serial fundus photographs, intravenous fluorescein angiography, and optical coherence tomography. RESULTS: We report the occurrence of lacquer crack in a 43-year-old woman with no history of trauma except for laser in situ keratomileusis surgery for mild myopia (as reported by the patient) in the past 5 years and habitual ocular rubbing. Lacquer crack started in the right eye and became evident 1 year later in the left eye. Serial photography after repeated intravitreal injections of ranibizumab for subfoveal choroidal new vessel showed the lacquer crack widened gradually in both eyes. Axial length measurement revealed the presence of high myopia. Best-corrected visual acuity dropped to 20/200 bilaterally. CONCLUSION: We hypothesize that a thin Bruch's membrane in high myopia is prone for small rupture initially either spontaneously or following laser in situ keratomileusis and subsequent widening of the rupture by oculopression and intravitreal injections from rise in intraocular pressure. PMID- 27186082 TI - Lyme disease caused by Borrelia burgdorferi with two homeologous 16S rRNA genes: a case report. AB - Lyme disease (LD), the most common tick-borne disease in North America, is believed to be caused exclusively by Borrelia burgdorferi sensu stricto and is usually diagnosed by clinical evaluation and serologic assays. As reported previously in a peer-reviewed article, a 13-year-old boy living in the Northeast of the USA was initially diagnosed with LD based on evaluation of his clinical presentations and on serologic test results. The patient was treated with a course of oral doxycycline for 28 days, and the symptoms resolved. A year later, the boy developed a series of unusual symptoms and did not attend school for 1 year. A LD specialist reviewed the case and found the serologic test band patterns nondiagnostic of LD. The boy was admitted to a psychiatric hospital. After discharge from the psychiatric hospital, a polymerase chain reaction test performed in a winter month when the boy was 16 years old showed a low density of B. burgdorferi sensu lato in the blood of the patient, confirmed by partial 16S rRNA (ribosomal RNA) gene sequencing. Subsequent DNA sequencing analysis presented in this report demonstrated that the spirochete isolate was a novel strain of B. burgdorferi with two homeologous 16S rRNA genes, which has never been reported in the world literature. This case report shows that direct DNA sequencing is a valuable tool for reliable molecular diagnosis of Lyme and related borrelioses, as well as for studies of the diversity of the causative agents of LD because LD patients infected by a rare or novel borrelial variant may produce an antibody pattern that can be different from the pattern characteristic of an infection caused by a typical B. burgdorferi sensu stricto strain. PMID- 27186084 TI - Functional role of the nicotinic arm of the acetylcholine regulatory axis in human B-cell lines. AB - We studied the involvement of nicotinic acetylcholine receptors (nAChRs) in the inflammation-related activity of human B-cell lines. Activation of nAChRs in Daudi cells with epibatidine abolished the pansorbin-dependent upregulation of the pro-inflammatory marker Cox-2 both at the mRNA and protein levels, indicating that the nicotinergic signaling suppresses B-cell activation. While the anti inflammatory action on B-cells was mediated predominantly through alpha7 nAChR, as could be judged from abolishing epibatidine effects with methyllycaconitine, both alpha7 and non-alpha7 nAChRs, such as alpha2-containing receptors, were involved in regulation of B-cell apoptosis. The net effect was antiapoptotic. To determine the role of nAChRs in regulating B-cell activation/plasmacytic differentiation, we measured changes in the CD38, CD138 and Bcl-6 gene expression. Epibatidine significantly (P < 0.05) upregulated CD38 at the transcriptional level and CD138 and Bcl-6 - at the translational levels. AR R17779 significantly (P < 0.05) increased the protein levels of CD38 and CD138. In both cases, the effect of epibatidine was abolished with Mec, and that of AR R17779 - by MLA, demonstrating a functional role of nAChRs in regulating Daudi cell differentiation. The obtained results revealed distinct contributions of alpha7 and non-alpha7 nAChRs to regulation of B-cell activation/differentiation, and suggested that signaling through the nicotinic arm of acetylcholine regulatory axis is important for B-cell involvement in inflammation. PMID- 27186085 TI - Effect of antiretroviral drugs on the pharmacodynamics of gliclazide with respect to glucose-insulin homeostasis in animal models. AB - The objective of this study was to investigate the effect of oral administration of antiretroviral drugs (indinavir, ritonavir, atazanavir, efavirenz and nevirapine) on the pharmacodynamics of gliclazide in rats (normal and diabetic) and rabbits with respect to glucose-insulin homeostasis to evaluate the safety and effectiveness of the combinations. Blood samples were collected at regular time intervals in rats from retro orbital puncture and by marginal ear vein puncture in rabbits. All the blood samples were analyzed for blood glucose by glucose oxidase-peroxidase method and insulin by a radio immuno assay method. The insulin resistance index and beta-cell function were determined by a homeostasis model assessment. Indinavir and ritonavir alone had significant impact on glucose insulin homeostasis in animal models among the antiretroviral drugs used in our study. In combination, indinavir and efavirenz significantly reduced the activity of gliclazide, while ritonavir and atazanavir significantly increased the activity of gliclazide. However, nevirapine had no significant effect on the activity of gliclazide. From this study we conclude that glucose-insulin homeostasis disorders associated with antiretroviral drugs are not class specific, but are drug-specific. So care should be taken when indinavir, ritonavir, atazanavir and efavirenz are prescribed for diabetic patients. PMID- 27186083 TI - Differential pharmacology and clinical utility of empagliflozin in type 2 diabetes. AB - With rates of obesity and diabetes rising across the world, effective therapies to treat hyperglycemia and its associated comorbidities continue to be in demand. Empagliflozin is a highly selective sodium glucose transporter-2 inhibitor that improves serum glucose levels by inducing glucosuria. Taken orally, it is rapidly absorbed with linear pharmacokinetics consistent in Asian and Caucasian populations. Empagliflozin treatment demonstrates consistent reductions in hemoglobin A1c, fasting plasma glucose, body weight, and blood pressure in individuals with type 2 diabetes. Improvements in glycemic control and metabolic end points are evident with empagliflozin monotherapy, as add-on to oral hypoglycemics or add-on to insulin. The nonglycemic effects of empagliflozin with consistent improvements in blood pressure, body weight, and waist circumference provide additional rationale for use in patients with type 2 diabetes. Moreover, treatment with empagliflozin has recently shown significant reductions in both microvascular and macrovascular complications of diabetes. PMID- 27186086 TI - Pilot safety evaluation of varenicline for the treatment of methamphetamine dependence. AB - Despite the worldwide extent of methamphetamine dependence, no medication has been shown to effectively treat afflicted individuals. One relatively unexplored approach is modulation of cholinergic system function. Animal research suggests that enhancement of central cholinergic activity, possibly at nicotinic acetylcholine receptors (nAChRs), can reduce methamphetamine-related behaviors. Further, preliminary findings indicate that rivastigmine, a cholinesterase inhibitor, may reduce craving for methamphetamine after administration of the drug in human subjects. We therefore performed a double-blind, placebo controlled, crossover pilot study of the safety and tolerability of varenicline in eight methamphetamine-dependent research subjects. Varenicline is used clinically to aid smoking cessation, and acts as a partial agonist at alpha4b2 nAChRs with full agonist properties at alpha7 nAChRs. Oral varenicline dose was titrated over one week to reach 1 mg twice daily, and then was co-administered with 30 mg methamphetamine, delivered in 10 intravenous (iv) infusions of 3 mg each. Varenicline was found to be safe in combination with iv methamphetamine, producing no cardiac rhythm disturbances or alterations in vital sign parameters. No adverse neuropsychiatric sequelae were detected either during varenicline titration or following administration of methamphetamine. The results suggest that varenicline warrants further investigation as a potential treatment for methamphetamine dependence. PMID- 27186087 TI - Cystone - An ayurvedic polyherbal formulation inhibits adherence of uropathogenic E. coli and modulates H2O2-induced toxicity in NRK-52E cells. AB - Gentamicin is a widely used antibiotic for the treatment of adverse urinary tract infections (UTI), which in turn causes nephrotoxicity to uroepithelial cells and hence an alternative safe herbal remedy is much desired to compensate these toxic effects. The bacterial adhesion to the uroepithelial cells is the primary step in UTI and it induces various immunogenic reactions leading to the generation of reactive oxygen species (ROS), which are detrimental to the cells survival. Inhibition of bacterial adherence to urinary tract epithelial cells has been assumed to account for the beneficial action ascribed to cystone (an ayurvedic polyherbal formulation) in the prevention of UTI. In this study, we have examined the effect of cystone on the adherence of pathogenic [2-(14)C]-acetate labeled Escherichia coli (MTCC-729) to rat proximal renal tubular cells (NRK-52E cells). Further, the antioxidant property of cystone was studied using hydrogen peroxide (400 MUM) as a pro-oxidant in NRK-52E cells. The results showed that cystone inhibited the adherence of E. coli to NRK-52E cells significantly. Additionally cystone effectively combats the toxicity induced by H2O2 in NRK-52E cells. The cytoprotective effect of cystone is brought about by inhibiting lipid peroxidation by 36% in cells treated with cystone compared to H2O2-treated cells without cystone. The antioxidant enzymes catalase, glutathione were increased by 53% and 68% respectively and superoxide dismutase activity was increased 3-fold. The glutathione content was significantly increased by 2.4-fold in NRK-52E cells treated with cystone compared to H2O2 control group. These results suggest that cystone effectively inhibits bacterial adherence to NRK-52E cells and attenuates H2O2-induced toxicity in NRK-52E cells by inhibiting lipid peroxidation and increasing the antioxidant defense mechanism. PMID- 27186088 TI - Potential antidiabetic and antioxidant activities of Morus indica and Asystasia gangetica in alloxan-induced diabetes mellitus. AB - Herbal drugs are frequently considered to be less toxic and also free from side effects, than synthetic ones. Hence, the present study was designed to investigate one such combination of herbal drugs, Asystasia gangetica and Morus indica for their antidiabetic and antioxidant potential against alloxan-induced diabetes in albino rats. The effect of both individual and a combination of Asystasia gangetica and Morus indica on blood glucose and liver glycogen were studied in the diabetic rats. The study also assessed for the effect of selected plant extracts for their effect on Superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and Lipid peroxidation (LPO) in the homogenates of the pancreas. The results of the present study attests significant antidiabetic and antioxidant potential for the selected plants individually and also in combination as a prominent decrease in blood glucose and liver glycogen was observed in the rats treated with the extracts of the selected plants. Similarly, the levels of the protective antioxidant enzymes like SOD, CAT and GSH were increased along with decrease in the LPO levels. The present study provides a scientific evidence for antidiabetic and antioxidant potential of Asystasia gangetica and Morus indica. Further studies to isolate bioactive compounds will pave the way to identify potential lead compounds for developing safe and efficacious antidiabetic agents. PMID- 27186089 TI - Cardioprotective and beta-adrenoceptor antagonistic activity of a newly synthesized aryloxypropanolamine derivative PP-36. AB - The present study was performed to evaluate the cardioprotective effects and pharmacological characterization of newly synthesized beta-adrenoreceptor antagonists 3-(3-tert-butylamino-2-hydroxypropoxy)-4-methoxybenzaldehyde (PP-36) in the rat model of coronary artery occlusion and reperfusion. Pre-ischemic administration (20 minutes before coronary occlusion) of PP-36 showed cardioprotective effects against ischemia/reperfusion injury in rats. PP-36 (6 mg kg(-1)) significantly reduced arrhythmia score (6.33 +/- 0.55, P < 0.05), infarct size/left ventricle size (38.9 +/- 3.2, P < 0.05) and no mortality compared to vehicle-treated control group (14.17 +/- 1.83, 44.9 +/- 4.6 and 17% respectively). In-vitro studies in rat isolated right atria, guinea-pig trachea and rat distal colon preparations, were carried out to investigate the potency of PP-36 towards different beta-adrenoceptor subtypes. pA2/pKB values of PP-36 for beta1-beta2-and beta3-adrenoceptors were 6.904 +/- 0.190, 6.44 +/- 0.129 and 5.773 +/- 0.129, respectively. In conclusion, PP-36 is a beta-adrenoceptor antagonist possessing potent anti-arrhythmic and cardioprotective effects against ischemia/reperfusion injury in rats. PMID- 27186092 TI - Nephroprotection of lacidipine against gentamycin-induced nephrotoxicity in albino rats. AB - AIM: Gentamycin, a widely-used aminoglycoside antibiotic, is recognized as possessing significant nephrotoxic potential in human beings. Gentamycin-induced nephrotoxicity is suggested to be mediated via reactive oxygen species. The present study investigated the possible antioxidant nephroprotective effect of lacidipine as a calcium-channel blocker in a gentamycin-induced nephrotoxicity model in albino rats. METHODS: Albino rats were divided into 3 groups. Group 1 received normal saline. Group 2 received gentamycin 80 mg/kg intraperitoneally for 14 days. Group 3 received lacidipine 1 mg/kg intraperitoneally 3 days before and 14 days concurrently with gentamycin. This dose does not affect the blood pressure of rats, as evidenced in the pilot study. RESULTS: Gentamycin-induced nephrotoxicity was evidenced by a marked reduction in creatinine clearance. Treatment with lacidipine improved creatinine clearance compared to the gentamycin-treated group. In addition, it reduced thiobarbituric acid reactive substance, as an index of lipid peroxidation, with significant increases in superoxide dismutase enzyme in erythrocyte lysates and kidney catalase enzyme activities. CONCLUSION: This study recommends the use of lacidipine in prophylaxis against gentamycin-induced nephrotoxicity. PMID- 27186091 TI - Effect of amlodipine, a calcium channel antagonist, on gonadal steroid of male Wistar albino rats. AB - This study was carried out to investigate the effect of prolonged intake of calcium-channel blocker amlodipine, an antihypertensive drug on gonadal steroid hormone (testosterone) of male albino rats. Three different concentrations of amlodipine (0.01, 0.02 and 0.03 mg/kg body weight) was administered orally to three different groups (B, C, and D) of experimental male Wistar albino rats (n = 8) for six weeks. Group A rats were fed normal diet without amlodipine (n = 8) served as the control. The administration of amlodipine significantly reduced testosterone level in the following order, group A (0.22 +/- 0.01) > B (0.18 +/- 0.01) > C (0.14 +/- 0.01) > D (0.10 +/- 0.01). The reduction in testosterone levels corresponded with an increase in the concentration of amlodipine administered to male Wistar albino rats. The observation in this study reveals that long-term treatment of male Wistar rats with calcium-channel blocker and antihypertensive (amlodipine) produces a significant reduction in the level of testosterone a hormone associated with decreased ability of men to enjoy sex and to develop good quality erections. There is the need for a large scale study to investigate the potential effect of long-term antihypertensive therapy with amlodipine on sexual dysfunction in men. PMID- 27186090 TI - Effects of an oral dose of l-glutamic acid on circulating neurotransmitters: Possible roles of the C1(Ad) and the A5(NA) pontomedullary nuclei. AB - OBJECTIVE: Investigation of the effects of an oral administration of a small dose of l-glutamic acid on the two peripheral sympathetic branches (neural and adrenal) of the autonomic nervous system. RESEARCH DESIGN AND METHODS: Circulating neurotransmitters and cardiovascular parameters were assessed in 28 healthy volunteers before and after the administration of 500 mg of l-glutamic acid or placebo. RESULTS: The drug triggered a significant and sustained enhancement of the noradrenaline and dopamine circulating levels which were paralleled and positively correlated with the diastolic blood pressure increases. Conversely, both platelet and plasma serotonin showed significant falls throughout the test. Significant positive correlations were registered between noradrenaline, dopamine, and noradrenaline/dopamine ratio versus diastolic blood pressure but not versus systolic blood pressure or heart rate. CONCLUSION: The above results allowed us to postulate that the drug provoked a significant enhancement of peripheral neural sympathetic activity and the reduction of adrenal sympathetic and parasympathetic drives. Both sympathetic branches are positively correlated with the A5 noradrenergic and the C1 adrenergic pontomedullary nuclei, which interchange inhibitory axons that act at post synaptic alpha2 inhibitory autoreceptors. In addition, we discussed the mechanisms able to explain why the drug acted preferentially at the A5 noradrenergic rather than the C1 adrenergic nuclei. PMID- 27186093 TI - Pharmacological modulation of brain levels of glutamate and GABA in rats exposed to total sleep deprivation. AB - Modulation of gamma-aminobutyric acid (GABA) and glutamate by selected antidepressants and anticonvulsants could play a beneficial role in total sleep deprivation (TSD) caused by depressed mood. In the present study, albino rats were exposed to TSD for five days. On the sixth day, the brains were removed, and GABA and glutamate levels were measured in the prefrontal cortex and thalamus to identify TSD-induced changes in untreated rats and in rats treated with carbamazepine 40 mg/kg intraperitoneally (IP), fluoxetine 20 mg/kg IP, or desipramine 10 mg/kg IP. Carbamazepine and fluoxetine significantly increased GABA and reduced glutamate levels in both brain areas. Desipramine administration did not affect GABA or glutamate concentrations in the tested brain areas; levels were comparable with those induced by TSD without treatment. These results suggest that administration of carbamazepine or fluoxetine could have a beneficial effect by increasing GABA levels during TSD. PMID- 27186094 TI - Pharmacogenomics of chronic hepatitis C therapy with genome-wide association studies. AB - Chronic hepatitis C (CHC) is a liver disease characterized by infection with the hepatitis C virus (HCV) persisting for more than six months. Patients with CHC often stop pursuing the pegylated interferon (peg-IFN) and ribavirin (RBV) treatment because of the high cost and associated adverse effects. Therefore, it is highly desirable, both clinically and economically, to establish the determinants of response to distinguish responders from nonresponders, and to predict the possible outcomes of the peg-IFN and RBV treatments. The aim of this study was to review recent data on the pharmacogenomics of the drug efficacy of IFN in CHC patients. Single nucleotide polymorphisms (SNPs) can be used to understand the relationship between genetic inheritance and IFN therapeutic response. In the recent advent of scientific research, the genome-wide association study (GWAS), which is an alternative to the candidate-gene approach, is widely utilized to examine hundreds of thousands of SNPs by high-throughput genotyping technologies. In addition to the candidate-gene approach, the GWAS approach has recently been employed to study the determinants of HCV's response to therapy. Several recent findings have demonstrated that some SNPs in the interleukin 28B gene are closely associated with IFN responsiveness. These results promise to lead to mechanistic findings related to IFN responsiveness in this disease, and will probably have major contributions for individualized medicine and therapeutic decision making. PMID- 27186096 TI - Clinical evaluation of a novel herbal dental cream in plaque formation: a double blind, randomized, controlled clinical trial. AB - BACKGROUND: The aim of this study was to evaluate the efficacy and safety of herbal dental cream in comparison to fluoride dental cream. OBJECTIVES: Clinical evaluation of a novel herbal dental cream in plaque formation: a double-blind, randomized, controlled clinical trial. METHODS: One hundred and two patients with established dental plaque were randomly assigned to either herbal dental group or fluoride dental group for six weeks in a double-blind design. Improvement in plaque index, oral hygiene status, bleeding index, and gingival index was evaluated in these patients along with microbiological study. RESULTS: Results indicated a significant reduction in plaque index, gingival index, oral hygiene index, and microbial growth in both groups. Difference between the groups was not significant. There was no significant change in bleeding index. No adverse events were reported and both the dental creams were well tolerated. CONCLUSION: The finding of this preliminary study indicates that herbal dental cream is as safe and effective as fluoride dental cream, but not superior to it. PMID- 27186095 TI - The influence of dexamethasone and the role of some antioxidant vitamins in the pathogenesis of experimental bronchial asthma. AB - BACKGROUND: Bronchial asthma is a disease characterized by paroxysmal and reversible obstruction of the airways. The imbalance between the oxidant and antioxidant system that is called oxidative stress is critical in asthma pathogenesis. It is likely, therefore, that antioxidants may be effective in the treatment of asthma. Systemic treatment with glucocorticoids has been reported to inhibit smooth muscle hypercontraction which may account partially for their beneficial effects in the treatment of asthma. OBJECTIVE: The present study was conducted in order to study the effect of dexamethasone and some antioxidant vitamins on interleukin-4 (IL-4), immunoglobulin E (IgE) and heat shock protein 70 (Hsp70) in bronchial asthma in rats, and to recognize their possible beneficial role. METHOD: The study was conducted on 60 adult male albino rats randomly divided into 4 groups (15 for each group): including normal control group (group A); asthma model group where rats were sensitized by ovalbumin and challenged with antigen aerosol producing bronchial asthma (group B); asthma model group treated with antioxidant vitamins (vitamin E and vitamin C) (group C); asthma model group treated with dexamethasone (group D). Blood and lung samples were collected from all groups. RESULTS AND CONCLUSION: Our results revealed a significant decrease of serum reduced glutathione (GSH) levels among groups B, C and D as compared to group A, while there was a significant increase in group C and D as compared to group B. Antioxidant and dexamethasone treatment resulted in a significant decrease of serum IL-4, malondialdehyde (MDA), and serum IgE levels in group C and D as compared to group B. Antioxidant treatment resulted in a significant decrease of serum Hsp70 level as compared to group B, while dexamethasone treatment resulted in a significant increase of serum Hsp70 level as compared to group B. This study suggests that it is likely that a combination of antioxidant vitamins may be effective in the treatment of asthma, considering their reported effects on lowering MDA, IL-4, and IgE levels, and the similar beneficial effects of dexamethasone in addition to increasing the expression of Hsp70 in the studied model of bronchial asthma. PMID- 27186097 TI - Effect of breastfeeding piperine on the learning of offspring mice: interaction with caffeine and diazepam. AB - Piperine, the main alkaloid of black pepper (Piper nigrum), has been suggested to display several pharmacological properties, including pain relief, anticonvulsant, antidepressant-like, antianxiety, sedative, and anti-inflammatory effects. This study was designed to investigate the effect of piperine on learning in mice and the interaction of the effect with caffeine and diazepam. Piperine (100 mg/kg intraperitoneally) was injected into the mouse mothers or nursing dams during breastfeeding for 25 days at five-day intervals. After feeding the newborn mice, their learning was evaluated using a step-through passive avoidance task. Mouse learning was assessed 1 hr and 24 hr and 1 week after a training session. Piperine increased learning in the first (1 hr: 243.33 s vs 55.17 s, P = 0.002) and third assessments (1 week: 226 s vs 97 s, P < 0.05) post-training, but no significant change was seen at the second (24 hr) assessment. Piperine improved the effect of a low dose of caffeine (25 mg/kg intraperitoneally after a shock of 2 s duration) in a first assessment (295.17 s vs 149.17 s, P = 0.026) compared to a higher dose of caffeine. Piperine reversed diazepam (1 mg/kg intraperitoneally) suppression of learning 24 hours after training by a 4 s shock (298 s vs 135.67 s, P = 0.03). According to the results, piperine alone significantly increased learning 1 hour and 1 week after training assessments, and learning can be improved in the short term when followed by piperine administration. It was also shown that piperine can potentiate the effect of a low dose of caffeine and can reverse the effect of diazepam. PMID- 27186099 TI - Cytoprotective effect of Semecarpus anacardium against toxicity induced by Streptozotocin in rats. AB - Leakage of cellular enzymes into the plasma is a clear indication of cell damage. When liver plasma membrane is damaged, a variety of enzymes normally located in the cytosol are released into the blood stream and their estimation is a quantitative marker for the extent of damage. The cytoprotective effect of Semecarpus anacardium was evaluated in rats that were rendered diabetic by administration of streptozotocin at a dose of 50 mg/kg body weight. The activities of the marker enzymes were assayed in the serum, liver and kidney. The indicators of renal damage such as urea, uric acid and creatinine were assayed in addition to the blood profile. The results of the present study reveal that Semecarpus anacardium was able to reverse the levels of the marker enzymes, and protect the kidney by reverting back to the normal levels of urea, uric acid, and creatinine. The abnormal blood parameters were also reverted to near normal levels indicating the drug's cytoprotective effect. PMID- 27186098 TI - Current and emerging therapies for the treatment of osteoporosis. AB - Osteoporosis represents a weakening of bone tissue due to an imbalance in the dynamic processes of bone formation and bone resorption that are continually ongoing within bone tissue. Most currently available osteoporosis therapies are antiresorptive agents. Over the past decade, bisphosphonates, notably alendronate and risedronate, have become the dominant agents with newer bisphosphonates such as ibandronate and zoledronic acid following a trend of less frequent dosing regimens. Synthetic estrogen receptor modulators (SERMs) continue to be developed as drugs that maintain the bone-protective effects of estrogen while avoiding its associated adverse side effects. Currently available agents of this class include raloxifene, the only SERM available in the United States (US), and lasofoxifene and bazedoxifene, available in Europe. Calcitonin, usually administered as a nasal spray, completes the list of currently approved antiresorptive agents, while parathyroid hormone analogs represent the only anabolic agents currently approved in both the US and Europe. Strontium ranelate is an additional agent available in Europe but not the US that has both anabolic and antiresorptive activity. New agents expected to further expand therapeutic options include denosumab, a monoclonal antibody inhibitor of the resorptive enzyme cathepsin K, which is in the final stages of Food and Drug Administration approval. Other agents in preclinical development include those targeting specific molecules of the Wnt/beta-catenin pathway involved in stimulating bone formation by osteoblast cells. This review discusses the use of currently available agents as well as highlighting emerging agents expected to bring significant changes to the approach to osteoporosis therapy in the near future. PMID- 27186101 TI - Recent advances in the treatment of multiple sclerosis. AB - Multiple sclerosis (MS) is a chronic inflammatory, immune-mediated, demyelinating, neurodegenerative disorder of the central nervous system. Despite the lack of an etiologic factor, it has been consistently demonstrated that the immune system plays a crucial role in the pathogenesis of MS. The traditional description of immunopathogenesis of MS suggests a preferential CD4+ TH1 cell activity causing tissue damage by the release of pro-inflammatory cytokines and subsequent demyelination and axonal loss. Recent evidence, however, suggests that other immune cells including TH17 cells, CD8+ effector T cells, CD4+ CD25+ regulatory T cells, and B cells may play a prominent role in MS immunopathology. A better understanding of the molecular and cellular components of the immunopathogenesis of MS is allowing the development of novel therapies. PMID- 27186100 TI - Effect of combined therapy of diabinese and nicotinic acid on liver enzymes in rabbits with dithizone-induced diabetes. AB - The effects of diabinese, a known antidiabetic drug, and the combined effects of diabinese and nicotinic acid, a vitamin and antilipidemic drug, were studied in rabbits with dithizone-induced diabetes. Side effects of diabinese include hypoglycemia and liver toxicity. Dithizone was used to induce partial experimental diabetes and to increase blood glucose significantly (P < 0.05) by 31.3%, 23.5%, 19.5, 24.7%, and 23.9% in groups A (single therapy of diabinese 10 mg/kg body weight), B (10 mg of diabinese and nicotinic acid 150 mg/kg), C (10 mg diabinese and nicotinic acid 200 mg/kg), D (10 mg diabinese and nicotinic acid 250 mg/kg) and E control (distilled water 5 mL), respectively. Dithizone administration also increased bilirubin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels by 28.9%-35.6%, 41.2%-54.8%, 40.1%-46.1%, and 60.9%-68.4%, respectively. Diabinese monotherapy reduced bilirubin levels, while combined therapy reduced glucose, ALP, AST, and ALT levels more than single therapy. Reduction from the hyperglycemic level 48 hours after drug administration was 20.0%, 24.6%, 41.0%, and 42.0% for groups A, B, C, and D, respectively, and was concentration-dependent. Also, combined therapy produced a significant (P < 0.05) decrease in AST and ALT levels, especially at 72 hours after drug administration, but did not affect ALP levels. No significant changes in glucose, bilirubin, ALP, AST, and ALT levels were observed in Group E (control). This study shows that liver toxicity and the hypoglycemic side effects of diabinese could be managed by the concomitant administration of nicotinic acid. PMID- 27186102 TI - Angiotensin (1-7)/Mas receptor axis activation ameliorates the changes in fatty acid composition in diabetic rats with nephropathy. AB - Diabetes mellitus is often associated with altered fatty acids composition. This study was designed to investigate the role of angiotensin (Ang) (1-7)/Mas receptor in improving fatty acids composition in streptozotocin (STZ)-induced diabetic nephropathy (DN) in rats. Rats treated with STZ (50 mg/kg, i.p. once) developed DN after 8 weeks. Fatty acid composition was estimated in renal cortical tissue by gas chromatography. Treatment with Ang (1-7), A-779, and Ang (1-7) plus A-779 was given from week 4 to week 8. Diabetic rats exhibited a significant increase in levels of saturated fatty acids and a significant decrease in levels of polyunsaturated fatty acids (PUFAs). Treatment with Ang (1 7) significantly attenuated these diabetes-induced changes. In diabetic rats, prior administration of A-779 significantly attenuated the increase in PUFAs produced by Ang (1-7); however, for saturated fatty acids, A-779 significantly blocked the decrease in palmitic acid only. Our study, for the first time, documented that endogenous Ang (1-7) modulates fatty acid composition in rats. Further, treatment with Ang (1-7) significantly attenuated diabetes-induced changes in fatty acids composition. This may be an additional mechanism implying the renoprotective role of Ang (1-7) in diabetic rats. PMID- 27186104 TI - Complexation of amphotericin B and curcumin with serum albumins: solubility and effect on erythrocyte membrane damage. AB - Amphotericin and curcumin are known to form complexes with albumins individually. In-silico analysis shows that amphotericin B and curcumin have separate binding regions on human serum albumin and bovine serum albumin. The complex formed with albumin in the presence of both amphotericin and curcumin is water soluble, and it retains antifungal activity. Interestingly, it was found that the presence of curcumin in the complex significantly delayed the red cell lysis by amphotericin B, indicating the possibility of moderating the toxic side effects of the drug using curcumin. Furthermore, since the presumed ternary complex is stable and water soluble, its potential use in the treatment of visceral leishmaniasis (kala azar) and systemic fungal infections needs to be evaluated. PMID- 27186103 TI - Effects of insulin resistance and testosterone on the participation of cyclooxygenase isoforms in vascular reactivity. AB - Testosterone plays an important role in mediating hypertension and altered vascular reactivity associated with insulin resistance. In addition to other pathways, testosterone-dependent changes in aortic cyclooxygenase (COX-2) mRNA levels affect blood pressure following insulin resistance. However their effects on vascular tone are unclear. We studied the changes in contraction response to phenylephrine (PE) in the aorta and superior mesenteric artery (SMA) from intact and gonadectomized fructose-fed rats. Constriction response to PE was studied in tissues incubated with the COX-1 and COX-2-selective antagonists, SC-560 and NS 398, respectively, and indomethacin, in addition to assessing its role in endothelium-dependent relaxation. Finally changes in COX-2 protein expression and plasma thromboxane A2 (TXA2), a downstream vasoconstrictor metabolite of COX-2, were measured. In fructose-fed rats, castration prevented the increase in blood pressure but not insulin resistance. The involvement of COX-2 in mediating the alpha-adrenergic vasoconstriction was higher in intact rat aorta compared to COX 1, which was prevented by castration. However, in the SMA, COX-2 participation was dependent on testosterone alone. Fructose-induced attenuation of endothelial relaxation was restored by indomethacin, which suggests a pro-vasoconstrictor role for COX. Both diet and testosterone did not alter vascular COX-2 expression thus suggesting the involvement of downstream testosterone-dependent pathways. This is supported by increased plasma TXA2 in the castrated rats compared to intact rats. Isoform-specific actions of COX are tissue-selective in states of insulin resistance and involve potential testosterone-dependent downstream targets. Further studies are needed to investigate the role of androgens and insulin resistance in vascular arachidonic acid metabolism. PMID- 27186105 TI - Role of calcium in morphine dependence and naloxone-precipitated withdrawal in mice. AB - PURPOSE: To explore the role of calcium in morphine withdrawal syndrome using various agents affecting calcium levels in cytoplasm. METHODS: Mice were rendered dependent on morphine by subcutaneous injection of morphine, and withdrawal was induced 4 hours later by injecting the opioid antagonist, naloxone. Mice were observed for 30 minutes for signs of withdrawal, ie, characteristic jumping, hyperactivity, urination, and diarrhea. Various calcium channel blockers were injected intraperitoneally 30 minutes before naloxone to evaluate their influence on the severity of the withdrawal syndrome. We also tested the effect of combination levodopa-carbidopa pretreatment and its interaction with a selective alpha-1 blocker, terazosin, on naloxone-precipitated withdrawal in mice acutely dependent on morphine. RESULTS: A significant dose-dependent attenuation of naloxone-induced morphine withdrawal syndrome was observed with calcium channel blockers, ie, verapamil 20 mg/kg (P < 0.05) and diltiazem 30 mg/kg (P < 0.01). Combination levodopa-carbidopa pretreatment facilitated the morphine withdrawal syndrome, and this was found to be blocked by terazosin, although not to a statistically significant (P > 0.05) extent. CONCLUSION: The results indicate that calcium plays an important role in the genesis of morphine dependence and withdrawal, and suggest the usefulness of calcium channel blockers in the management of morphine withdrawal syndrome. PMID- 27186106 TI - Investigational new drugs in the treatment of inflammatory bowel disease: a review. AB - The unraveling of the immuno-pathobiology of inflammatory bowel disease (IBD) in the past three decades has ushered in a new era of translational medicine. The biotechnology revolution has resulted in a paradigm shift in how clinicians view and treat IBD. Anti-tumor necrosis factor (TNF)-alpha strategies using infliximab and adalimumab currently dominate the therapeutic arena. Better understanding of how these biologicals work is driving the quest for loftier therapeutic goals of achieving mucosal healing, sustaining deep remission, and even modifying the natural history of IBD. However, not all patients respond to anti-TNF drugs. Immune-mediated adverse reactions and loss of efficacy with time also limit their use. There are many investigational drugs undergoing active clinical trials. Many have not fulfilled their early promises but some are potentially making the transition from bench to trial and to the bedside in the near future. Clinicians and investigators need to underpin our excitement with caution for the unknown long-term consequences of modulating cytokines and selective adhesion molecules in human. Here we provide an overview of investigational new drugs and other therapeutic strategies currently undergoing clinical trials in IBD. PMID- 27186108 TI - Preparation of ultrasound microbubbles crosslinked to albumin nanoparticles packaged with tissue-type plasminogen activator gene plasmid and method of in vivo transfection. AB - AIMS: To observe the effect of constructed ultrasound microbubble crosslinked to albium nanoparticles packaged with tissue-type plasminogen activator (tPA) gene plasmid on the in vivo transfection. METHODS: The rabbits were chosen for all experiments. A highly expressive gene plasmid for tPA was constructed and packaged into a prepared nanoparticle with bovine serum albumin (BSA). This albium nanoparticle packaged with tPA gene plasmid was crosslinked to an ultrasound microbubble prepared with BSA and sucrose to form a nano-targeting vector system for tPA gene transfection. The transfection and effective expression of tPA in heart, liver, leg skeletal muscle and the cervical rib were detected with polyclonal antibodies to tPA using immunohistochemical method; the tPA level and D-dimer content of blood were also tested. RESULTS: The expression of tPA could be seen in the tissues mentioned above, with the increase in blood tPA level and D-dimer content from 0.20 +/- 0.05 ug/L and 81.76 +/- 9.84 ug/L before the operation, to the higher levels of 0.44 +/- 0.05 ug/L and 669.28 +/- 97.74 ug/L after transfection. CONCLUSION: The nano-targeting vector system for tPA gene was contructed successfully. This provides a new theory and experimental method for the nano-targeted transgene. PMID- 27186107 TI - Novel compounds in the treatment of lung cancer: current and developing therapeutic agents. AB - Lung cancer is the leading cause of cancer-related death in the United States. Though incremental advances have been made in the treatment of this devastating disease during the past decade, new therapies are urgently needed. Traditional cytotoxic agents have been combined with other modalities with improved survival for early-stage patients. Newer cytotoxic agents targeting the same or different mechanisms have been developed at different stages. Optimization of various chemotherapy regimens in different settings is one of the aims of current clinical trials. Some predictive biomarkers (eg, excision repair cross complementing 1, ERCC1) and histotypes (eg, adenocarcinoma) are found to be associated with resistance/response to some cytotoxic drugs. Another notable advance is the addition of targeted therapy to lung cancer treatment. Targeted agents such as erlotinib and bevacizumab have demonstrated clinical benefits and gained Food and Drug Administration approval for lung cancer. More agents targeting various signaling pathways critical to lung cancer are at different stages of development. Along with the effort of new targeted drug discovery, biomarkers such as epidermal growth factor receptor and anaplastic lymphoma kinase mutations have proven useful for patient selection, and more predictive biomarkers have been actively evaluated in non-small cell lung cancer. The paradigm of lung cancer treatment has shifted towards biomarker-based personalized medicine. PMID- 27186109 TI - Comparison of the effects of the oral anticancer platinum(IV) complexes oxoplatin and metabolite cis-diammine-tetrachlorido-platinum(IV) on global gene expression of NCI-H526 cells. AB - Platinum(IV) coordination complexes like oxoplatin (cis,cis,trans-diammine dichlorido-dihydroxido-platinum[IV]) show high stability and therefore can be utilized orally for outpatient care. Although oxoplatin is capable of binding directly to DNA after prolonged incubation, platinum(IV) agents are considered to be largely inert prodrugs that are converted to highly cytotoxic platinum(II) compounds by reducing substances, enzymes, or microenviron-mental conditions. Reaction of oxoplatin with 0.1 M hydrogen chloride mimicking gastric acid yields cis-diammine-tetrachlorido-platinum(IV) (DATCP[IV]), which exhibits two-fold increased activity. The presence of chlorides as ligands in the axial position results in a high reduction potential that favors transformation to platinum(II) complexes. In this study, the intracellular effect of the highly reactive tetrachlorido derivative was investigated in comparison with an equipotent dose of cisplatin. Genome-wide expression profiling of NCI-H526 small cell lung cancer cells treated with these platinum species revealed clear differences in the expression pattern of affected genes and concerned cellular pathways between DATCP(IV) and cisplatin. Application of DATCP(IV) resulted in extensive downregulation of protein and ATP synthesis, cell cycle regulation, and glycolysis, in contrast to cisplatin, which preferentially targeted glutathione conjugation, pyruvate metabolism, citric acid cycle, and the metabolism of amino acids and a range of carbohydrates. Thus, the oxoplatin metabolite DATCP(IV) constitutes a potent cytotoxic derivative that may be produced by gastric acid or acidic areas prevailing in larger solid tumors, depending on the respective pharmaceutical formulation of oxoplatin. Furthermore, DATCP(IV) exhibits intracellular effects that are clearly different from the expected reduced product cisplatin(II). In conclusion, activation of the platinum(IV) complex oxoplatin seems to involve the generation of a cytotoxic six-coordinate species, dependent on prevailing conditions, and its effects need to be considered in addition to the effects of the potential final platinum(II) product. PMID- 27186110 TI - Effects of single-dose morning and evening administration of pravastatin on antioxidant markers in cholesterol-fed rabbits. AB - BACKGROUND: Accurate timing of statin administration is considered important to obtain the best hypolipidemic effect. Pravastatin is one of the currently prescribed hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, and was chosen in this study to evaluate its antioxidant effect when administered as a single daily dose in the morning versus evening in cholesterol-fed rabbits. METHODS: This 12-week study was performed in New Zealand rabbits, divided into four groups (n = 6 each), ie, normocholesterolemic controls; cholesterol 1% diet, nontreated ; cholesterol 1% diet treated with pravastatin in the morning; and cholesterol 1% diet treated with pravastatin in the evening. Plasma total cholesterol levels, superoxide dismutase enzyme levels in erythrocyte lysates, thiobarbituric acid-reactive substance content, catalase, and glutathione enzyme activity in liver homogenates from the tested rabbits were measured. RESULTS: Both morning and evening treatment with pravastatin significantly improved all the measured antioxidant markers in comparison with nontreated cholesterol-fed rabbits. However, results obtained with evening dosing were better than with morning dosing. CONCLUSION: The antioxidant profile of pravastatin is better when the drug is administered in the evening rather than in the morning. PMID- 27186111 TI - The essential oils component p-cymene induces proton leak through Fo-ATP synthase and uncoupling of mitochondrial respiration. AB - Essential oils can be used as antimicrobial, antioxidant, and anticarcinogenic agents or to preserve and give flavors to foods. The activity of phenolic-rich essential oils has been observed in fractions containing thymol and carvacrol which show synergistic effects with their precursor p-cymene. Their mode of action is related to several targets in the cell but specific mechanisms of activity and cytotoxic effects remain poorly characterized. Given the importance of mitochondria for cellular functions and their critical role in a vast number of diseases, this work evaluated the effects of p-cymene on mitochondrial functions. It was observed that p-cymene did not change the oxygen consumption by respiratory chain (state 2 respiration). However, p-cymene decreased the mitochondrial membrane potential (Deltapsi), depressed the rate of ADP phosphorylation (state 3), and stimulated the oxygen consumption after phosphorylation of ADP (state 4). The respiratory control ratio (state 3/state 4) was decreased as a consequence of the inhibition of state 3 and stimulation of state 4 respiration but the ADP/O index remained unaltered as well as the mitochondrial Ca(2+) fluxes. Moreover, p-cymene did not induce mitochondrial membrane disruption but depressed the Deltapsi, and the stimulatory effect observed on state 4, similar to the effect observed on state 2 respiration plus ATP, was inhibited by oligomycin. These effects suggest that p-cymene allows a proton leak through the Fo fraction of the phosphorylative system, changing the mitochondrial proton motive force and ATP synthesis capacity. Therefore, these data suggest mitochondria as a target for p-cymene toxicity action mechanisms. PMID- 27186112 TI - Restoration of renal hemodynamics and functions during black cumin (Nigella sativa) administration in streptozotocin-induced diabetic rats. AB - BACKGROUND: Black cumin (Nigella sativa) is an ancient herbal medicine recommended by the World Health Organization. The antioxidant and antihyperglycemic effects of black cumin are well established. Amelioration of renal dysfunction in nephrotoxic rats with black cumin treatment has also been noted. However, the effect of black cumin treatment on renal dysfunction in diabetes mellitus has not been clarified. In this study, the effect of black cumin oil (BC) on changes in renal dysfunction and renal hemodynamics in streptozotocin-induced diabetic rats was evaluated. METHODS: The experiments were performed in male Sprague Dawley rats, divided into four groups (seven in each group): (1) normal rats given tap water (CON); (2) normal rats administered with BC (CON-BC); (3) diabetic rats given tap water only (STZ); and (4) diabetic rats administered with BC (STZ-BC). Diabetes mellitus was induced in the rats by an injection of streptozotocin. BC was given orally at the dose of 1000 mg/kg body weight to the rat in either CON-BC or STZ-BC every day for 8 weeks. Renal hemodynamics and functions in each rat were studied. RESULTS: Renal hemodynamic changes in STZ-BC rats appeared to increase in terms of glomerular filtration rate, effective renal plasma flow, and effective renal blood flow, while renal vascular resistance and filtration fraction were decreased in comparison with diabetic rats given tap water only (STZ). An improvement of renal tubular dysfunction in STZ-BC rats was indicated by the decreases in fractional excretion of water and Mg(++). CONCLUSION: An administration of BC can restore changes in renal hemodynamics and renal dysfunction in streptozotocin-induced diabetic rats. PMID- 27186114 TI - Hibiscus sabdariffa L., roselle calyx, from ethnobotany to pharmacology. AB - Using MEDLINE and SCOPUS databases, a review of the literature from the pioneering study of 1991 until 2010 was performed on the effects on biological models of Hibiscus sabdariffa L. roselle calyx, its extracts mainly in polar solvents, or pure components found in extracts, as well as their possible relationship to these effects. Three relevant effects on lipid metabolism, antihypertensive activity, and apoptosis were observed. Our chronological review of the studies mentioned in the literature provides another opportunity to see how humans compile scientific knowledge of a chemical structure-physiological activity relationship starting from an ethnobotanical-ethnopharmagognosy contribution. The chemical components that are the main active principles in the physiological activities of Hibiscus sabdariffa L. calyx are anthocyanins and polyphenols (protocatechuic acid and quercetin). Advances have also been made in the elucidation of action mechanisms. Additionally, it has become clear that the lack of standardization in terms of chemical components of the material arising from Hibiscus sabdariffa L. used in testing on biological models imposes limits on the possibility of carrying out comparative analyses between studies. Fortunately, more recent studies are overcoming this obstacle by reporting component concentrations of assumed active principles; however, complete analysis of the extract, if this is to be considered as a therapeutic agent, is not commonly reported in the aforesaid studies. If one of the eventual scenarios for Hibiscus sabdariffa L. calyx is as a therapeutic agent in communities with economic limitations, then studies of a pharmacological nature should guarantee the effectiveness, safety, and tolerability of this material, which is widely accepted to be associated with chemical complexity, thus making this knowledge necessary. PMID- 27186113 TI - Flavonoids as GABAA receptor ligands: the whole story? AB - Benzodiazepines are the most widely prescribed class of psychoactive drugs in current therapeutic use, despite the important unwanted side effects that they produce, such as sedation, myorelaxation, ataxia, amnesia, and ethanol and barbiturate potentiation and tolerance. They exert their therapeutic effects via binding to the benzodiazepine binding site of gamma-aminobutyric acid (GABA) type A receptors, and allosterically modulating the chloride flux through the ion channel complex. First isolated from plants used as tranquilizers in folkloric medicine, some natural flavonoids have been shown to possess selective affinity for the benzodiazepine binding site with a broad spectrum of central nervous system effects. Since the initial search for alternative benzodiazepine ligands amongst the flavonoids, a list of successful synthetic derivatives has been generated with enhanced activities. This review provides an update on research developments that have established the activity of natural and synthetic flavonoids on GABA type A receptors. Flavonoids are prominent drugs in the treatment of mental disorders, and can also be used as tools to study modulatory sites at GABA type A receptors and to develop GABA type A selective agents further. PMID- 27186115 TI - Antiarthritic effect of aqueous and ethanolic leaf extracts of Pistia stratiotes in adjuvant-induced arthritis in Sprague-Dawley rats. AB - BACKGROUND: Pistia stratiotes has been used effectively to treat a number of inflammatory conditions. This study aims to determine the antiarthritic effect of aqueous and ethanolic leaf extracts of P. stratiotes. METHODS: Arthritis was induced in Sprague-Dawley rats, paw swelling was measured, and arthritis indices were estimated in rats treated with aqueous and ethanolic leaf extracts of P. stratiotes (AQ PSE and ET PSE, respectively), methotrexate, diclofenac, dexamethasone, and normal saline-treated rats. Radiologic imaging, hematological assessment of red and white blood cells, C-reactive protein and erythrocyte sedimentation rate, as well as histopathological studies were also done. The data were analyzed using GraphPad Prism 5. RESULTS: The 30, 100, and 300 mg/kg doses of AQ PSE and the 30 and 100 mg/kg doses of ET PSE caused a significant (P <= 0.05-0.001) reduction in ipsilateral paw swelling, similar to the effects of methotrexate, dexamethasone, and diclofenac. Only the 30 mg/kg dose of AQ PSE caused a significant (P <= 0.01) reduction in contralateral paw swelling. Arthritic indices reduced significantly (P <= 0.05-0.001) at all drug doses, except for the 100 and 300 mg/kg doses of ET PSE. White blood cell levels decreased significantly (P <= 0.05-0.01) in arthritic rats treated with the 30 mg/kg dose of AQ PSE and those treated with methotrexate. Erythrocyte sedimentation rate and C-reactive protein levels were significantly (P <= 0.01 0.001) lower in all the treatment groups except for the rats treated with AQ PSE 300 mg/kg and ET PSE 100 and 300 mg/kg doses. The arthritic animals treated with 30 mg/kg of the aqueous extract showed no inflammatory changes in the ipsilateral paw, while the contralateral paw showed only foci of mild chronic inflammatory changes, as seen with the reference drug treatment in histopathological studies. CONCLUSION: This study establishes that aqueous and ethanolic extracts of P. stratiotes have antiarthritic activity in Sprague-Dawley rats with induced arthritis. The aqueous extract had better activity than the ethanolic extract. PMID- 27186116 TI - A quantitative way to estimate clinical off-target effects for human membrane brain targets in CNS research and development. AB - Although many preclinical programs in central nervous system research and development intend to develop highly selective and potent molecules directed at the primary target, they often act upon other off-target receptors. The simple rule of taking the ratios of affinities for the candidate drug at the different receptors is flawed since the affinity of the endogenous ligand for that off target receptor or drug exposure is not taken into account. We have developed a mathematical receptor competition model that takes into account the competition between active drug moiety and the endogenous neurotransmitter to better assess the off-target effects on postsynaptic receptor activation under the correct target exposure conditions. As an example, we investigate the possible functional effects of the weak off-target effects for dopamine-1 receptor (D1R) in a computer simulation of a dopaminergic cortical synapse that is calibrated using published fast-cyclic rodent voltammetry and human imaging data in subjects with different catechol-O-methyltransferase genotypes. We identify the conditions under which off-target effects at the D1R can lead to clinically detectable consequences on cognitive tests, such as the N-back working memory test. We also demonstrate that certain concentrations of dimebolin (Dimebon), a recently tested Alzheimer drug, can affect D1R activation resulting in clinically detectable cognitive decrease. This approach can be extended to other receptor systems and can improve the selection of clinical candidate compounds by potentially dialing out harmful off-target effects or dialing-in beneficial off-target effects in a quantitative and controlled way. PMID- 27186117 TI - The efficacy of stingless bee honey for the treatment of bacteria-induced conjunctivitis in guinea pigs. AB - The efficacy of the conjunctival application of a crude concentration of stingless bee honey (SBH) for the treatment of bacterial conjunctivitis was investigated in an animal model. Bacterial conjunctivitis caused by Staphylococcus aureus or Pseudomonas aeruginosa was induced in Hartley guinea pigs. The conjunctival application of SBH or gentamicin was used for treatment, and the results of this treatment were compared with control values. Inflammatory signs, duration of infection (ie, positive culture), and time for the complete resolution of infection with S. aureus or P. aeruginosa were shortened by the conjunctival application of 1 drop (70 uL) of crude SBH twice daily. The potency of SBH was comparable with that of gentamicin. SBH may be a rational agent for the treatment of infective conjunctivitis in humans; it is inexpensive and commonly available to the rural population. PMID- 27186118 TI - Oseltamivir reduces hippocampal abnormal EEG activities after a virus infection (influenza) in isoflurane-anesthetized rats. AB - BACKGROUND: Oseltamivir phosphate (OP, Tamiflu((r))) is a widely used drug in the treatment of influenza with fever. However, case reports have associated OP intake with sudden abnormal behaviors. In rats infected by the influenza A virus (IAV), the electroencephalogram (EEG) displayed abnormal high-voltage amplitudes with spikes and theta oscillations at a core temperature of 39.9 degrees C to 41 degrees C. Until now, there has been no information describing the effect of OP on intact brain hippocampal activity of IAV-infected animals during hyperthermia. OBJECTIVE: The aim of the present study was to examine the effect of OP on abnormal EEG activities in the hippocampus using the rat model of influenza associated encephalopathy. METHODS: Male Wistar rats aged 3 to 4 weeks were used for the study. Influenza A/WSN/33 strain (1 * 10(5) plaque forming unit in PBS, 60 uL) was applied intranasally to the rats. To characterize OP effects on the IAV-infected rats, EEG activity was studied more particularly in isoflurane anesthetized IAV-infected rats during hyperthermia. RESULTS: We found that the hippocampal EEG of the OP-administered (10 mg/kg) IAV-infected rats showed significant reduction of the high-voltage amplitudes and spikes, but the theta oscillations, which had been observed only at >40 degrees C in OP non administered rats, appeared at 38 degrees C core temperature. Atropine (30 mg/kg) blocked the theta oscillations. CONCLUSION: Our data suggest that OP efficiently reduces the abnormal EEG activities after IAV infection during hyperthermia. However, OP administration may stimulate ACh release in rats at normal core temperature. PMID- 27186119 TI - The extracellular signal-regulated kinase (ERK) pathway: a potential therapeutic target in hypertension. AB - Hypertension is a risk factor for myocardial infarction, stroke, renal failure, heart failure, and peripheral vascular disease. One feature of hypertension is a hyperresponsiveness to contractile agents, and inhibition of vasoconstriction forms the basis of some of the treatments for hypertension. Hypertension is also associated with an increase in the growth and proliferation of vascular smooth muscle cells, which can lead to a thickening of the smooth muscle layer of the blood vessels and a reduction in lumen diameter. Targeting both the enhanced contractile responses, and the increased vascular smooth muscle cell growth could potentially be important pharmacological treatment of hypertension. Extracellular signal-regulated kinase (ERK) is a member of the mitogen-activated protein kinase family that is involved in both vasoconstriction and vascular smooth muscle cell growth and this, therefore, makes it attractive therapeutic target for treatment of hypertension. ERK activity is raised in vascular smooth muscle cells from animal models of hypertension, and inhibition of ERK activation reduces both vascular smooth muscle cell growth and vasoconstriction. This review discusses the potential for targeting ERK activity in the treatment of hypertension. PMID- 27186120 TI - Investigational agents in the treatment of Parkinson's disease: focus on safinamide. AB - The authors review management issues in Parkinson's disease (PD) and provide an overview of the current pharmacological management strategies, with a specific focus on safinamide. Current therapeutic management of PD largely involves strategies to optimize the replacement of deficient dopamine, using levodopa, dopamine agonists, and inhibitors of dopamine-metabolizing enzymes. Currently under investigation for use in the treatment of PD, safinamide has multiple modes of action including monoamine oxidase B inhibition. It is well absorbed orally, has a long plasma half-life, and does not have liver enzyme-inducing or liver enzyme-inhibiting activity. Peak plasma concentration occurs 2-4 hours after single oral doses. Safinamide as monotherapy and as an adjunct to dopamine agonists improves Unified Parkinson's Disease Rating Scale motor scores. One randomized, placebo-controlled trial involving 168 patients given a median safinamide dose of 70 mg/day (range 40-90 mg/day) significantly increased the proportion of responders - defined as patients improving their Unified Parkinson's Disease Rating Scale motor scores by 30% or more from baseline - after 3 months (37.5% for safinamide versus 21.4% for placebo; P < 0.05). Safinamide increased "on" time with no or minor dyskinesia compared with the placebo in another trial, but dyskinesia severity was not reduced. Safinamide was well tolerated, with an adverse effect profile similar to that of the placebo. Further Phase III trial data for safinamide efficacy is awaited, and will be of interest in a comparison with other developments in PD therapeutics: modified formulations of available compounds, new drug classes such as adenosine receptor antagonists, and gene-based therapies. PMID- 27186121 TI - Reduction in cancer risk by selective and nonselective cyclooxygenase-2 (COX-2) inhibitors. AB - We conducted a series of epidemiologic studies to evaluate the chemopreventive effects of aspirin, ibuprofen, and selective cyxlooxygenase-2 (COX-2) inhibitors (coxibs) against cancers of the breast, colon, prostate, and lung. Composite results across all four cancer sites revealed that regular intake of 325 mg aspirin, 200 mg ibuprofen, or standard dosages of coxibs (200 mg celecoxib or 25 mg rofecoxib) produced risk reductions of 49%, 59%, and 64%, respectively. Use of coxibs for at least 2 years was associated with risk reductions of 71%, 70%, 55%, and 60% for breast cancer, colon cancer, prostate cancer and lung cancer, respectively. Effects of ibuprofen were similar to selective coxibs, and slightly stronger than aspirin. These observed effects are consistent with the relative COX-2 selectivity of ibuprofen, coxibs, and aspirin. Acetaminophen, an analgesic without COX-2 activity, had no effect. Overexpression of COX-2 and increased prostaglandin biosynthesis correlates with carcinogenesis and metastasis at most anatomic sites. These results indicate that regular intake of nonselective or selective COX-2 inhibiting agents protects against the development of major forms of cancer. PMID- 27186122 TI - Investigational agents in metastatic basal cell carcinoma: focus on vismodegib. AB - Vismodegib (GDC-0449, 2-chloro-N-(4-chloro-3-(pyridin-2-yl)phenyl)-4 (methylsulfonyl)benzamide, ErivedgeTM) is a novel first-in-human, first-in class, orally bio-available Hedgehog pathway signaling inhibitor of the G-protein coupled receptor-like protein smoothened (SMO) which was approved in the United States on January 2012. This signaling pathway is involved in the carcinogenesis of several types of tumor, as exemplified by basal cell carcinoma. This review focuses on the role of the Hedgehog pathway in the pathogenesis of basal cell carcinoma, the pharmacology and the clinical activity of vismodegib, as well as a brief summary of investigational agents in development targeting this pathway. PMID- 27186123 TI - Action of AferBio (fermented food) in a rat inflammatory model. AB - BACKGROUND: AferBio is a fermented prebiotic food that contains beta-glucans, which are oligosaccharides capable of stimulating the proliferation of beneficial bacteria in the gastrointestinal tract. The aim of this study was to evaluate the possible effects of this functional food on the inflammatory response in rats. METHODS AND RESULTS: AferBio (900 mg/kg) inhibited edema formation by 34% compared to the control group. We also observed inhibition of the primary and secondary reactions of inflammation after the injection of Freund's adjuvant in the animals fed AferBio. Daily administration of AferBio for 6 d inhibited the formation of granulomatous tissue by 37%; additionally, inhibition of 31% of neutrophil migration downstream of carrageenan-induced peritonitis was observed. An ulcerogenic potency assay revealed that indomethacin produced a higher number of lesions compared to treatment with AferBio. Anti-inflammatory potency analysis showed that indomethacin inhibited 39% of carrageenan-induced edema but produced a higher number of lesions. However, animals treated with AferBio had areas of hyperemia without ulcerative lesions and 21% of edema was inhibited. CONCLUSION: Based on the results obtained in this study, AferBio appears to have anti inflammatory activity during acute and chronic inflammatory processes. PMID- 27186124 TI - The pharmacology and therapeutic potential of (-)-huperzine A. AB - (-)-Huperzine A (1) is an alkaloid isolated from a Chinese club moss. Due to its potent neuroprotective activities, it has been investigated as a candidate for the treatment of neurodegenerative diseases, including Alzheimer's disease. In this review, we will discuss the pharmacology and therapeutic potential of (-) huperzine A (1). Synthetic studies of (-)-huperzine A (1) aimed at enabling its development as a pharmaceutical will be described. PMID- 27186125 TI - Ouabain inhibits monocyte activation in vitro: prevention of the proinflammatory mCD14(+)/CD16(+) subset appearance and cell-size progression. AB - Classically described as a potent inhibitor of the sodium-potassium adenosine triphosphatase enzyme, ouabain has been further shown to act as an effective immunomodulator in mammals. Recently, our group showed that this hormone downregulates membrane CD14 (mCD14) in human monocytes, though it is not known whether monocyte activation status could modify ouabain influence. Hence, we aimed to investigate ouabain effect during monocyte activation in vitro, analyzing mCD14, CD16 and CD69 expression in total monocytes after two periods of adhesion (2 hours and 24 hours) or in small and large monocyte subpopulations separately. Ouabain (100 nM) inhibited monocyte-size increase, characteristic of activation, only when added to cells immediately after 2 hours' adhesion. Moreover, downregulation of both mCD14 and CD16 expression by ouabain was more effective in small monocytes and in cells after 2 hours' adhesion. Since monocytes after 24 hours' adhesion showed no lack of ouabain binding and no CD69 upregulation, it seems that ouabain is somehow incapable of triggering an appropriate cell-signaling induction once monocytes become activated. Furthermore, though p38 MAPK activation was crucial for the impairment in cell size progression induced by ouabain, its inhibition did not alter ouabain-induced CD69 upregulation, suggesting that other molecules may participate in the response to this hormone by monocytes. Our data suggest that ouabain inhibits monocyte activation in vitro, preventing both cell-size increase and the appearance of the proinflammatory mCD14(+)/CD16(+) subpopulation. Thus, the findings suggest that individuals suffering from disorders commonly associated with high ouabain plasma levels, like hypertension, may present defective monocyte activation under inflammation or infection. PMID- 27186126 TI - The therapeutic potential of RORgamma modulators in the treatment of human disease. AB - Nuclear receptors (NR) are ligand-regulated transcription factors that bind DNA in proximity to their target genes and exert their effects as a result of binding by small molecule ligands such as sterols, lipids, fatty acids, retinoids, and steroid hormones. The retinoic acid receptor-related orphan receptors or RORs (NR1F1-NR1F3) are nuclear receptors that regulate multiple cellular processes, including metabolism, cellular differentiation, and apoptosis, in a range of tissues and organs. These receptors bind as monomers to ROR response elements commonly called ROREs present in promoter regions of target genes and tether chromatin remodeling enzymes, facilitating recruitment of transcription machinery. Several recent reports have highlighted the potential role for RORs in human disease, and more importantly, studies have demonstrated that these receptors can be modulated by exogenous synthetic ligands, paving the way for development of novel therapeutics. Here we review the current status of synthetic ligand development as well as the structural aspects governing modulation of ROR signaling pathways as they relate to metabolic diseases and autoimmune disorders. PMID- 27186127 TI - Efficacy of ipamorelin, a ghrelin mimetic, on gastric dysmotility in a rodent model of postoperative ileus. AB - BACKGROUND: Delayed gastric emptying is a common disorder with few effective therapeutic options. The goal of this study was to investigate whether ipamorelin, a synthetic peptidomimetic that acts on the ghrelin receptor, accelerates gastric emptying in a rodent model of gastroparesis induced by abdominal surgery and intestinal manipulation. METHODS: Fasted adult male rats were subjected to laparotomy and intestinal manipulation. Following the surgery rats received ipamorelin (0.014-0.14 umol/kg) or vehicle control via intravenous administration. Gastric emptying was measured by the percent of total recovered radioactivity remaining in the stomach 15 minutes after intragastric gavage of 1.5 mL of (99m)Tc (technicium-99m) sulfur colloid in 0.5% methylcellulose. In a separate group of rats subjected to laparotomy and intestinal manipulation, the gastric fundus was isolated and tissue segments were suspended in an organ bath to assess the effect of ipamorelin (1 uM) on gastric smooth muscle contractility induced by acetylcholine and electrical field stimulation. RESULTS: Abdominal surgery caused a delay in gastric emptying with 78% +/- 5% of the meal remaining in the stomach in vehicle controls. Ipamorelin (0.014 umol/kg intravenous) resulted in a significant acceleration (P < 0.05 vs vehicle-treated rat) of gastric emptying with 52% +/- 11% of the meal remaining in the stomach compared to nonsurgical control animals with 44% +/- 6%. Following abdominal surgery and intestinal manipulation, isolated preparations of gastric smooth muscle exhibited a marked inhibition of acetylcholine and electrical field stimulation-induced contractile responses, which were reversed by ipamorelin and ghrelin. CONCLUSION: These results suggest that ipamorelin accelerates gastric emptying in a rodent model of postoperative ileus through the stimulation of gastric contractility by activating a ghrelin receptor-mediated mechanism involving cholinergic excitatory neurons. PMID- 27186128 TI - The anticancer activity of dichloromethane crude extract obtained from Calea pinnatifida. AB - The genus Calea is reported for many biological activities such as antiinflammatory, antiplasmodial, antifungal, antimicrobial, and cytotoxic activities. Most of the pharmacological activities are credited to germacranolides, a sesquiterpene lactone common to this genus. Dried aerial parts of Calea pinnatifida Banks were extracted with dichloromethane, which generated the dichloromethane crude extract (DCE). The main purpose of this study was to evaluate the anticancer activity of DCE performed in sulforhodamine B cytotoxicity in vitro assay against human cancer cell lines and in vivo Ehrlich models. The DCE showed a high potency and selectivity for the melanoma and kidney cell line. Two in vivo assays were also conducted in the Ehrlich ascites tumor and Ehrlich solid tumor. In the Ehrlich ascites tumor assay, the treatment with DCE increased survival rates at the highest dose (200 mg/kg). Interestingly, in the Ehrlich solid tumor, by increasing the number of treatments from one to three times a week, the tumor growth was inhibited by a lower dose (100 mg/kg). These results encouraged follow-up studies with C. pinnatifida in order to identify the active principles and to determine the anticancer mechanism of action. PMID- 27186129 TI - Effectiveness of nootropic drugs with cholinergic activity in treatment of cognitive deficit: a review. AB - Nootropics represent probably the first "smart drugs" used for the treatment of cognitive deficits. The aim of this paper is to verify, by a systematic analysis of the literature, the effectiveness of nootropics in this indication. The analysis was limited to nootropics with cholinergic activity, in view of the role played by acetylcholine in learning and memory. Acetylcholine was the first neurotransmitter identified in the history of neuroscience and is the main neurotransmitter of the peripheral, autonomic, and enteric nervous systems. We conducted a systematic review of the literature for the 5-year period 2006-2011. From the data reported in the literature, it emerges that nootropics may be an effective alternative for strengthening and enhancing cognitive performance in patients with a range of pathologies. Although nootropics, and specifically the cholinergic precursors, already have a long history behind them, according to recent renewal of interest, they still seem to have a significant therapeutic role. Drugs with regulatory indications for symptomatic treatment of Alzheimer's disease, such as cholinesterase inhibitors and memantine, often have transient effects in dementia disorders. Nootropics with a cholinergic profile and documented clinical effectiveness in combination with cognate drugs such as cholinesterase inhibitors or alone in patients who are not suitable for these inhibitors should be taken into account and evaluated further. PMID- 27186131 TI - Morphine treatment alters nucleotidase activities in rat blood serum. AB - Morphine has been widely used in neonatal pain management. However, this treatment may produce adaptive changes in several physiologic systems. Our laboratory has demonstrated that morphine treatment in neonate rats alters nucleoside triphosphate diphosphohydrolase (NTPDase) activity and gene expression in central nervous system structures. Considering the relationship between the opioid and purinergic systems, our aim was to verify whether treatment with morphine from postnatal days 8 (P8) through 14 (P14) at a dose of 5 ug per day alters NTPDase and 5'-nucleotidase activities in rat serum over the short, medium, and long terms. After the in vivo assay, the morphine group showed increased hydrolysis of all nucleotides at P30, and a decrease in adenosine 5' diphosphate hydrolysis at P60. Moreover, we found that nucleotidase activities change with age; adenosine 5'-triphosphate hydrolysis activity was lower at P16, and adenosine 5'-monophosphate hydrolysis activity was higher at P60. These changes are very important because these enzymes are the main regulators of blood nucleotide levels and, consequently, nucleotide signaling. Our findings showed that in vivo morphine treatment alters nucleotide hydrolysis in rat blood serum, suggesting that purine homeostasis can be influenced by opioid treatment during the neonatal period. PMID- 27186130 TI - Hedgehog signaling pathway and its targets for treatment in basal cell carcinoma. AB - Basal cell carcinoma (BCC) of the skin is the most common type of cancer and accounts for up to 40% of all cancers in the US, with a growing incidence rate over recent decades in all developed countries. Surgery is curative for most patients, although it leaves unaesthetic scars, but those that develop locally advanced or metastatic BCC require different therapeutic approaches. Furthermore, patients with BCC present a high risk of developing additional tumors. The increasing economic burden and the morbidity of BCC render primary interest in the development of targeted treatments for this disease. Among the molecular signals involved in the development of BCC, the critical role of the morphogenetic Hedgehog (Hh) pathway has become evident. This pathway is found altered and activated in almost all BCCs, both sporadic and inherited. Given the centrality of the Hh pathway in the pathophysiology of BCC, the primary efforts to identify molecular targets for the topical or systemic treatment of this cancer have focused on the Hh components. Several Hh inhibitors have been so far identified - from the first identified natural cyclopamine to the recently Food and Drug Administration-approved synthetic vismodegib - most of which target the Hh receptor Smoothened (either its function or its translocation to the primary cilium). Other molecules await further characterization (bisamide compounds), while drugs currently approved for other diseases such as itraconazole (an antimicotic agent) and vitamin D3 have been tested on BCC with encouraging results. The outcomes of the numerous ongoing clinical trials are expected to expand the field in the very near future. Further research is needed to obtain drugs targeting downstream components of the Hh pathway (eg, Gli) or to exploit combinatorial therapies (eg, with phosphatidylinositol 3-kinase inhibitors or retinoids) in order to overcome potential drug resistance. PMID- 27186132 TI - Role of GLUT4 on angiotensin 2-induced systemic and renal hemodynamics. AB - Cross-talk between insulin and the renin angiotensin system signaling system shows that angiotensin 2 (A2) negatively modulates insulin signaling by stimulating multiple serine phosphorylation events in the early stages of the insulin-signaling cascade; however, the biological actions of A2 on insulin sensitivity remain controversial. Preservation of glucose transporter 4 (GLUT4) expression during hypertension has been shown to prevent the increased vascular reactivity associated with hypertension. This study tested the hypothesis that GLUT4 contributes to the renal actions of A2. In the euvolemic anesthetized rat, acute infusion of the GLUT4 antagonist, indinavir (1 mg/kg/minute), enhanced an A2-induced increase in mean arterial blood pressure (MABP) (P < 0.01), but attenuated an A2-induced increase in medullary blood flow (MBF) and glomerular filtration rate (P < 0.01). Insulin, a GLUT4 activator (20 mU/kg/minute and 40 mU/kg/minute), decreased basal MABP and urine volume (P < 0.05), but it increased MBF, and these effects were reversed and blunted by indinavir. Subchronic indinavir treatment (80 mg/kg/day orally for 15 days) did not affect A2-induced changes in MABP, cortical blood flow, and MBF, but significantly decreased basal MBF (P < 0.01) and global kidney perfusion (P < 0.05). We concluded that acute but not subchronic inhibition of GLUT4 alters A2-induced changes in systemic and renal hemodynamics by attenuating A2-induced increase in MBF and glomerular filtration rate. PMID- 27186133 TI - Pharmacology and rationale for imatinib in the treatment of scleroderma. AB - Systemic sclerosis (scleroderma) is a chronic, multisystem, fibrotic disease. Although the pathogenesis is not completely understood, early vascular damage leads to an inflammatory reaction and a severe fibrotic response. Therapy of systemic sclerosis is still not convincing and is mainly restricted to the management of organ complications. A wide choice of immunosuppressive and antifibrotic drugs has been used to try to modify the course of the disease, but significant breakthroughs are still lacking. Imatinib is a tyrosine kinase inhibitor known to regulate growth, proliferation, and differentiation as well as apoptosis of cells and is already widely used for several malignancies, eg, chronic myeloid leukemia and gastrointestinal stromal tumors. It has been used in preclinical as well as clinical studies to modulate the fibrotic process in patients with systemic sclerosis. This is based on its activity to interfere selectively with both the transforming growth factor-beta and platelet-derived growth factor signaling pathway. Preclinical studies in mouse models of scleroderma showed significant anti-inflammatory and antifibrotic effects; however, several clinical, proof-of-concept trials have not yet confirmed these initially promising results. PMID- 27186135 TI - Progress toward therapeutic potential for AFQ056 in Fragile X syndrome. AB - Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and the leading single-gene cause of autism. It is caused by the lack of production of the Fragile X mental retardation protein (FMRP), resulting in cognitive deficits, hyperactivity, and autistic behaviors. Breakthrough advances in potential therapy for FXS followed the discovery that aberrant group 1 metabotropic glutamate receptor (mGluR) signaling is an important constituent of the pathophysiology of the syndrome. Research has indicated that upon neuronal stimulation, FMRP acts downstream of group 1 mGluRs (mGluRs1/5) to inhibit protein synthesis, long-term depression, and alpha-amino-3-hydroxy-5-methyl-4 isoxazolepropionic acid receptor internalization. To offset the deficits caused by the lack of FMRP, many pharmaceutical companies have designed medicinal drugs to target the unrestrained stimulation of mGluR5 signaling in FXS. Indeed, promising results from animal and clinical studies suggest that mGluR5 antagonists such as AFQ056 can successfully correct many of the deficits in FXS. In this review, we cover the animal studies performed to date that test the role of AFQ056 as a selective mGluR5 antagonist to alleviate the phenotypes of FXS. PMID- 27186136 TI - Uptake of tenofovir and emtricitabine into non-monocytic female genital tract cells with and without hormonal contraceptives. AB - BACKGROUND: Pre-exposure prophylaxis is becoming a strategic component used to control the human immunodeficiency virus (HIV-1) epidemic. The goal of this study was to characterize intracellular uptake of tenofovir and emtricitabine using five surrogate cell lines of the female genital tract and determine whether exogenous hormones influence their uptake. METHODS: Surrogate cell lines, ie, THP 1 (representing macrophages), BC-3 (CD8+), Ect1/E6E7 (squamous epithelial), HeLa (CD4+), and TF-1 (dendritic), were incubated for one hour with tenofovir and emtricitabine to assess uptake. In separate experiments, ethinyl estradiol (EE) and etonogestrel (ET) individually and together (EE/ET) were added prior to, simultaneously, and after incubation. Intracellular phosphorylated tenofovir and emtricitabine were quantified using validated tandem mass spectrometry methods. RESULTS: HeLa and Ect1/E6E7 cells showed significantly increased uptake relative to THP-1 controls for both antiretrovirals. Individually, ethinyl estradiol and etonogestrel significantly altered antiretroviral uptake across all cell lines, except Ect1/E6E7 for tenofovir and HeLa for emtricitabine. Cellular uptake of tenofovir and emtricitabine in BC-3 and TF-1 cells were significantly lower when dosed one hour prior to EE/ET administration compared with each antiretroviral administered in the absence of EE/ET (tenofovir, 80 versus 470 fmol/10(6) for BC 3 and 77 versus 506 fmol/10(6) cells for TF-1; emtricitabine, 36 versus 12 fmol/10(6) for BC-3 and 75 versus 5 fmol/10(6) cells for TF-1; P < 0.01 for each). CONCLUSION: These data suggest that intracellular uptake of tenofovir and emtricitabine within the female genital tract varies by cell type and in the presence of hormonal contraceptives. The potential clinical implications of these findings should be further evaluated in vivo. PMID- 27186137 TI - Effect of anions or foods on absolute bioavailability of calcium from calcium salts in mice by pharmacokinetics. AB - We studied the absolute bioavailability of calcium from calcium L-lactate in mice using pharmacokinetics, and reviewed the absolute bioavailability of calcium from three other calcium salts in mice previously studied: calcium chloride, calcium acetate, and calcium ascorbate. The results showed that calcium metabolism is linear between intravenous administration of 15 mg/kg and 30 mg/kg, and is not affected by anions. Results after oral calcium administration of 150 mg/kg showed that the intestinal absorption process was significantly different among the four calcium salts. The rank of absolute bioavailability of calcium was calcium ascorbate > calcium L-lactate >= calcium acetate > calcium chloride. The mean residence time (MRTab) of calcium from calcium ascorbate (32.2 minutes) in the intestinal tract was much longer than that from calcium L-lactate (9.5 minutes), calcium acetate (15.0 minutes) and calcium chloride (13.6 minutes). Furthermore, the foods di-D-fructo-furanose-1,2':2,3'-dianhydride, sudachi (Citrus sudachi) juice, and moromi-su (a Japanese vinegar) increased the absolute bioavailability of calcium from calcium chloride by 2.46-fold, 2.86-fold, and 1.23-fold, respectively, and prolonged MRTab by 48.5 minutes, 43.1 minutes, and 44.9 minutes, respectively. In conclusion, the prolonged MRTab of calcium in the intestinal tract by anion or food might cause the increased absorbability of calcium. PMID- 27186134 TI - Curcumin: a natural substance with potential efficacy in Alzheimer's disease. AB - Curcumin is a component of turmeric, a spice used in many types of cooking. Epidemiological evidence suggesting that populations that eat food with a substantial amount of curcumin were at lower risk of Alzheimer's disease (AD) led to the idea that this compound might have a neuroprotective effect. Curcumin has substantial antioxidant and anti-inflammatory effects, and is being used as a potential preventative agent or treatment for many types of cancer. There is evidence to suggest that the addition of curcumin to cultured neuronal cells decreases brain inflammation and protects against beta-amyloid-induced neurotoxicity. Curcumin also protects against toxicity when beta-amyloid is administered to produce animal models of AD. Curcumin decreases beta-amyloid formation from amyloid precursor protein, and also inhibits aggregation of beta amyloid into pleated sheets. Studies in transgenic mice with overproduction of beta-amyloid demonstrate a neuroprotective effect of curcumin as well. Cognitive function was also improved in these animal models. Clinical trials of curcumin in AD have not been very promising. It is possible that this is due to poor oral bioavailability of curcumin in humans, and thus several approaches are being developed to improve delivery systems or to create analogs that will mimic the neuroprotective effects and easily reach the brain. The lack of efficacy of curcumin in humans with AD may also result from treating for too short a time or starting treatment too late in the course of the disease, where substantial neuronal death has already occurred and cannot be reversed. Curcumin may be beneficial in protecting against development or progression of AD if taken over the long term and started before symptoms of AD become apparent. PMID- 27186138 TI - Clevidipine resistance in a patient taking aripiprazole and methylphenidate. AB - Various factors may be responsible for blood pressure alterations during perioperative care. When these physiologic alterations require treatment, several therapeutic options are available. Clevidipine is an ultrashort-acting, intravenous L-type calcium channel antagonist of the dihydropyridine class. Anecdotal experience has demonstrated its efficacy in various clinical scenarios in the pediatric population. We report apparent resistance to the vasodilatory effects of clevidipine in a 13-year-old girl who presented for anesthetic care during posterior spinal fusion for neuromuscular scoliosis whose chronic medication regimen included aripiprazole and methylphenidate for the treatment of depression and attention-deficit/hyperactivity disorder. We discuss the potential interaction of aripiprazole and methylphenidate with the calcium channel antagonists and cellular mechanisms responsible for the resistance to the vasodilatory effects of clevidipine. PMID- 27186139 TI - BiochronomerTM technology and the development of APF530, a sustained release formulation of granisetron. AB - Granisetron and other 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists are first-line agents for preventing chemotherapy-induced nausea and vomiting (CINV). Current treatment guidelines prefer the longer-acting agent, palonosetron, for CINV prevention in some chemotherapy regimens. A new granisetron formulation, APF530, has been developed as an alternative long-acting agent. APF530 utilizes Biochronomer(TM) technology to formulate a viscous tri(ethylene glycol) poly(orthoester)-based formulation that delivers - by single subcutaneous (SC) injection - therapeutic granisetron concentrations over 5 days. The poly(orthoester) polymer family contain an orthoester linkage; these bioerodible polymer systems are specifically designed for controlled, sustained drug delivery. Pharmacokinetics and pharmacodynamics of APF530 250, 500, or 750 mg SC (granisetron 5, 10, or 15 mg, respectively) administered 30-60 minutes before chemotherapy were evaluated in two Phase II trials in cancer patients receiving moderately (MEC) or highly (HEC) emetogenic chemotherapy. Pharmacokinetics were dose proportional, with slow granisetron absorption and elimination. Both trials demonstrated similar results for median half-life, time to maximum concentration, and exposure for APF530 250 and 500 mg, with no differences between patients receiving MEC or HEC. A randomized Phase III trial demonstrated noninferiority of APF530 500 mg SC (granisetron 10 mg) to intravenous palonosetron 0.25 mg in preventing CINV in patients receiving MEC or HEC in acute (0-24 hours) and delayed (24-120 hours) settings, with activity over 120 hours. Mean maximum granisetron plasma concentrations were 10.8 and 17.8 ng/mL, and mean half-lives were 30.8 and 35.9 hours after SC administration of APF530 250 and 500 mg, respectively. Therapeutic granisetron concentrations were maintained for greater than 120 hours (5 days) in both APF530 dose groups. These data suggest that APF530 - an SC-administered formulation of granisetron delivered via Biochronomer technology - represents an effective treatment option for the prevention of both acute and delayed CINV in patients receiving either MEC or HEC. PMID- 27186140 TI - Single exposure of dopamine D1 antagonist prevents and D2 antagonist attenuates methylphenidate effect. AB - Methylphenidate (MPD) is a readily prescribed drug for the treatment of attention deficit hyperactivity disorder (ADHD) and moreover is used illicitly by youths for its cognitive-enhancing effects and recreation. MPD exposure in rodents elicits increased locomotor activity. Repetitive MPD exposure leads to further augmentation of their locomotor activity. This behavioral response is referred to as behavioral sensitization. Behavioral sensitization is used as an experimental marker for a drug's ability to elicit dependence. There is evidence that dopamine (DA) is a key player in the acute and chronic MPD effect; however, the role of DA in the effects elicited by MPD is still debated. The objective of this study was to investigate the role of D1 and/or D2 DA receptors in the acute and chronic effect of MPD on locomotor activity. The study lasted for 12 consecutive days. Seven groups of male Sprague Dawley((r)) rats were used. A single D1 or D2 antagonist was given before and after acute and chronic MPD administration. Single injection of D1 DA antagonist was able to significantly attenuate the locomotor activity when given prior to the initial MPD exposure and after repetitive MPD exposure, while the D2 DA antagonist partially attenuated the locomotor activity only when given before the second MPD exposure. The results show the role, at least in part, of the D1 DA receptor in the mechanism of behavioral sensitization, whereas the D2 DA receptor only partially modulates the response to acute and chronic MPD. PMID- 27186141 TI - Antihyperalgesic effects of ProTx-II, a Nav1.7 antagonist, and A803467, a Nav1.8 antagonist, in diabetic mice. AB - The present study investigated the effects of intrathecal administration of ProTx II (tarantula venom peptide) and A803467 (5-[4-chloro-phenyl]-furan-2-carboxylic acid [3,5-dimethoxy-phenyl]-amide), selective Nav1.7 and Nav1.8 antagonists, respectively, on thermal hyperalgesia in a painful diabetic neuropathy model of mice. Intrathecal administration of ProTx-II at doses from 0.04 to 4 ng to diabetic mice dose-dependently and significantly increased the tail-flick latency. Intrathecal administration of A803467 at doses from 10 to 100 ng to diabetic mice also dose-dependently and significantly increased the tail-flick latency. However, intrathecal administration of either ProTx-II (4 ng) or A803467 (100 ng) had no effect on the tail-flick latency in nondiabetic mice. The expression of either the Nav1.7 or Nav1.8 sodium channel protein in the dorsal root ganglion in diabetic mice was not different from that in nondiabetic mice. The present results suggest that ProTx-II and A803467, highly selective blockers of Nav1.7 and Nav1.8 sodium channels, respectively, in the spinal cord, can have antihyperalgesic effects in diabetic mice. PMID- 27186142 TI - Current knowledge on the neuroprotective and neuroregenerative properties of citicoline in acute ischemic stroke. AB - Ischemic stroke is one of the leading causes of long-lasting disability and death. Two main strategies have been proposed for the treatment of ischemic stroke: restoration of blood flow by thrombolysis or mechanical thrombus extraction during the first few hours of ischemic stroke, which is one of the most effective treatments and leads to a better functional and clinical outcome. The other direction of treatment, which is potentially applicable to most of the patients with ischemic stroke, is neuroprotection. Initially, neuroprotection was mainly targeted at protecting gray matter, but during the past few years there has been a transition from a neuron-oriented approach toward salvaging the whole neurovascular unit using multimodal drugs. Citicoline is a multimodal drug that exhibits neuroprotective and neuroregenerative effects in a variety of experimental and clinical disorders of the central nervous system, including acute and chronic cerebral ischemia, intracerebral hemorrhage, and global cerebral hypoxia. Citicoline has a prolonged therapeutic window and is active at various temporal and biochemical stages of the ischemic cascade. In acute ischemic stroke, citicoline provides neuroprotection by attenuating glutamate exitotoxicity, oxidative stress, apoptosis, and blood-brain barrier dysfunction. In the subacute and chronic phases of ischemic stroke, citicoline exhibits neuroregenerative effects and activates neurogenesis, synaptogenesis, and angiogenesis and enhances neurotransmitter metabolism. Acute and long-term treatment with citicoline is safe and in most clinical studies is effective and improves functional outcome. PMID- 27186143 TI - Aryl hydrocarbon receptor antagonism and its role in rheumatoid arthritis. AB - Although rheumatoid arthritis (RA) is the most common autoimmune disease, affecting approximately 1% of the population worldwide, its pathogenic mechanisms are poorly understood. Tobacco smoke, an environmental risk factor for RA, contains several ligands of aryl hydrocarbon receptor (Ahr), also known as dioxin receptor. Ahr plays critical roles in the immune system. We previously demonstrated that Ahr in helper T-cells contributes to development of collagen induced arthritis, a mouse model of RA. Other studies have shown that cigarette smoke condensate and pure Ahr ligands exacerbate RA by altering bone metabolism and inducing proinflammatory responses in fibroblast-like synoviocytes. Consistent with these findings, several Ahr antagonists such as alpha naphthoflavone, resveratrol, and GNF351 reverse the effect of Ahr ligands in RA pathogenesis. In this review, we summarize the current knowledge of Ahr function in the immune system and the potential clinical benefits of Ahr antagonism in treating RA. PMID- 27186145 TI - Changes in blood biochemical markers before, during, and after a 2-day ultramarathon. AB - We studied changes in blood markers of 18 nonprofessional, middle-aged runners of a 2-day, 130 km ultramarathon. Blood was sampled at baseline, after the goals on the first and second day, and at three time points (1, 3, and 5/6 days) after the race. Blood indices showed three patterns. First pattern indices showed essentially no changes after the two goals and after the race, including red blood cell indices, gamma-glutamyl transferase, and tumor necrosis factor-alpha. Second pattern markers, including the majority of indices, were elevated during the race (and also after the race for some parameters) and then returned to baseline afterward, including hemolysis/red blood cell destruction markers (indirect bilirubin) and an iron reservoir index (ferritin), muscle damage parameters (uric acid, creatine kinase, lactate dehydrogenase, and aspartate aminotransferase), renal function markers (creatinine and blood urea nitrogen), liver injury index (alanine aminotransferase), lipid metabolism indices (free fatty acid), reactive oxygen species and inflammation parameters (white blood cells, interleukin-6, and C-reactive protein), and energy production and catecholamines (adrenaline, noradrenaline, and dopamine). Third pattern index of a lipid metabolism marker - triglyceride - decreased during the race periods and started returning to baseline from then onward. Some hormonal markers such as insulin, leptin, and adiponectin showed unique patterns. These findings appeared informative for nonprofessional athletes to know about an optimal physical activity level, duration, and total exercise for elevating physical performance and monitoring physical/mental conditioning as well as for prevention of overtraining and physical injuries. PMID- 27186146 TI - Coping with occupational stress: the role of optimism and coping flexibility. AB - The current study aimed at measuring whether coping flexibility is a reliable and valid construct in a UK sample and subsequently investigating the association between coping flexibility, optimism, and psychological health - measured by perceived stress and life satisfaction. A UK university undergraduate student sample (N=95) completed an online questionnaire. The study is among the first to examine the validity and reliability of the English version of a scale measuring coping flexibility in a Western population and is also the first to investigate the association between optimism and coping flexibility. The results revealed that the scale had good reliability overall; however, factor analysis revealed no support for the existing two-factor structure of the scale. Coping flexibility and optimism were found to be strongly correlated, and hierarchical regression analyses revealed that the interaction between them predicted a large proportion of the variance in both perceived stress and life satisfaction. In addition, structural equation modeling revealed that optimism completely mediated the relationship between coping flexibility and both perceived stress and life satisfaction. The findings add to the occupational stress literature to further our understanding of how optimism is important in psychological health. Furthermore, given that optimism is a personality trait, and consequently relatively stable, the study also provides preliminary support for the potential of targeting coping flexibility to improve psychological health in Western populations. These findings must be replicated, and further analyses of the English version of the Coping Flexibility Scale are needed. PMID- 27186144 TI - The pathophysiology of thrombocytopenia in chronic liver disease. AB - Thrombocytopenia is the most common hematological abnormality encountered in patients with chronic liver disease (CLD). In addition to being an indicator of advanced disease and poor prognosis, it frequently prevents crucial interventions. Historically, thrombocytopenia has been attributed to hypersplenism, which is the increased pooling of platelets in a spleen enlarged by congestive splenomegaly secondary to portal hypertension. Over the past decade, however, there have been significant advances in the understanding of thrombopoiesis, which, in turn, has led to an improved understanding of thrombocytopenia in cirrhosis. Multiple factors contribute to the development of thrombocytopenia and these can broadly be divided into those that cause decreased production, splenic sequestration, and increased destruction. Depressed thrombopoietin levels in CLD, together with direct bone marrow suppression, result in a reduced rate of platelet production. Thrombopoietin regulates both platelet production and maturation and is impaired in CLD. Bone marrow suppression can be caused by viruses, alcohol, iron overload, and medications. Splenic sequestration results from hypersplenism. The increased rate of platelet destruction in cirrhosis also occurs through a number of pathways: increased shear stress, increased fibrinolysis, bacterial translocation, and infection result in an increased rate of platelet aggregation, while autoimmune disease and raised titers of antiplatelet immunoglobulin result in the immunologic destruction of platelets. An in-depth understanding of the complex pathophysiology of the thrombocytopenia of CLD is crucial when considering treatment strategies. This review outlines the recent advances in our understanding of thrombocytopenia in cirrhosis and CLD. PMID- 27186148 TI - Midostaurin: an emerging treatment for acute myeloid leukemia patients. AB - Acute myeloid leukemia (AML) is a hematologic malignancy that carries a poor prognosis and has garnered few treatment advances in the last few decades. Mutation of the internal tandem duplication (ITD) region of fms-like tyrosine kinase (FLT3) is considered high risk for decreased response and overall survival. Midostaurin is a Type III receptor tyrosine kinase inhibitor found to inhibit FLT3 and other receptor tyrosine kinases, including platelet-derived growth factor receptors, cyclin-dependent kinase 1, src, c-kit, and vascular endothelial growth factor receptor. In preclinical studies, midostaurin exhibited broad-spectrum antitumor activity toward a wide range of tumor xenografts, as well as an FLT3-ITD-driven mouse model of myelodysplastic syndrome (MDS). Midostaurin is orally administered and generally well tolerated as a single agent; hematologic toxicity increases substantially when administered in combination with standard induction chemotherapy. Clinical trials primarily have focused on relapsed/refractory AML and MDS and included single- and combination agent studies. Administration of midostaurin to relapsed/refractory MDS and AML patients confers a robust anti-blast response sufficient to bridge a minority of patients to transplant. In combination with histone deacetylase inhibitors, responses appear comparable to historic controls, while the addition of midostaurin to standard induction chemotherapy may prolong survival in FLT3-ITD mutant patients. The response of some wild-type (WT)-FLT3 patients to midostaurin therapy is consistent with midostaurin's ability to inhibit WT-FLT3 in vitro, and also may reflect overexpression of WT-FLT3 in those patients and/or off-target effects such as inhibition of kinases other than FLT3. Midostaurin represents a well-tolerated, easily administered oral agent with the potential to bridge mutant and WT-FLT3 AML patients to transplant and possibly deepen response to induction chemotherapy. Ongoing studies are investigating midostaurin's role in pretransplant induction and posttransplant consolidation therapy. PMID- 27186147 TI - Neurophysiological basis of rapid eye movement sleep behavior disorder: informing future drug development. AB - Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by a history of recurrent nocturnal dream enactment behavior and loss of skeletal muscle atonia and increased phasic muscle activity during REM sleep: REM sleep without atonia. RBD and associated comorbidities have recently been identified as one of the most specific and potentially sensitive risk factors for later development of any of the alpha-synucleinopathies: Parkinson's disease, dementia with Lewy bodies, and other atypical parkinsonian syndromes. Several other sleep-related abnormalities have recently been identified in patients with RBD/Parkinson's disease who experience abnormalities in sleep electroencephalographic frequencies, sleep-wake transitions, wake and sleep stability, occurrence and morphology of sleep spindles, and electrooculography measures. These findings suggest a gradual involvement of the brainstem and other structures, which is in line with the gradual involvement known in these disorders. We propose that these findings may help identify biomarkers of individuals at high risk of subsequent conversion to parkinsonism. PMID- 27186150 TI - Deaf adolescents in a hearing world: a review of factors affecting psychosocial adaptation. AB - Adolescence has long been viewed as a time of rapid change in many domains including physical, cognitive, and social. Adolescents must adapt based on developing skills and needs and acclimate to growing environmental pressures. Deaf adolescents are often faced with the additional challenge of managing these adaptations in a hearing world, where communication and access to information, especially about their social world, are incomplete at best and nonexistent at worst. This article discusses the research on several factors that influence a deaf adolescent's adaptation, including quality of life, self-concept, and identity development. Gaps in our knowledge are pointed out with suggestions for future research programs that can facilitate optimal development in adolescents who are deaf. PMID- 27186149 TI - Psychological predictors of headache remission in children and adolescents. AB - OBJECTIVE: Longitudinal studies on headaches often focus on the identification of risk factors for headache occurrence or "chronification". This study in particular examines psychological variables as potential predictors of headache remission in children and adolescents. METHODS: Data on biological, social, and psychological variables were gathered by questionnaire as part of a large population-based study (N=5,474). Children aged 9 to 15 years who suffered from weekly headaches were selected for this study sample, N=509. A logistic regression analysis was conducted with remission as the dependent variable. In the first step sex, age, headache type, and parental headache history were entered as the control variables as some data already existed showing their predictive power. Psychological factors (dysfunctional coping strategies, internalizing symptoms, externalizing symptoms, anxiety sensitivity, somatosensory amplification) were entered in the second step to evaluate their additional predictive value. RESULTS: Highly dysfunctional coping strategies reduced the relative probability of headache remission. All other selected psychological variables reached no significance, ie, did not contribute additionally to the explanation of variance of the basic model containing sex and headache type. Surprisingly, parental headache and age were not predictive. The model explained only a small proportion of the variance regarding headache remission (R(2) =0.09 [Nagelkerke]). CONCLUSION: Successful coping with stress in general contributed to remission of pediatric headache after 2 years in children aged between 9 and 15 years. Psychological characteristics in general had only small predictive value. The issue of remission definitely needs more scientific attention in empirical studies. PMID- 27186151 TI - Development of a novel sports medicine rotation for emergency medicine residents. AB - Musculoskeletal complaints are the most common reason for patients to visit a physician, yet competency in musculoskeletal medicine is invariably reported as a deficiency in medical education in the USA. Sports medicine clinical rotations improve both medical students' and residents' musculoskeletal knowledge. Despite the importance of this knowledge, a standardized sports medicine curriculum in emergency medicine (EM) does not exist. Hence, we developed a novel sports medicine rotation for EM residents to improve their musculoskeletal educational experience and to improve their knowledge in musculoskeletal medicine by teaching the evaluation and management of many common musculoskeletal disorders and injuries that are encountered in the emergency department. The University of Arizona has two distinct EM residency programs, South Campus (SC) and University Campus (UC). The UC curriculum includes a traditional 4-week orthopedic rotation, which consistently rated poorly on evaluations by residents. Therefore, with the initiation of a new EM residency at SC, we replaced the standard orthopedic rotation with a novel sports medicine rotation for EM interns. This rotation includes attendance at sports medicine clinics with primary care and orthopedic sports medicine physicians, involvement in sport event coverage, assigned reading materials, didactic experiences, and an on-call schedule to assist with reductions in the emergency department. We analyzed postrotation surveys completed by residents, postrotation evaluations of the residents completed by primary care sports medicine faculty and orthopedic chief residents, as well as the total number of dislocation reductions performed by each graduating resident at both programs over the last 5 years. While all residents in both programs exceeded the ten dislocation reductions required for graduation, residents on the sports medicine rotation had a statistically significant higher rate of satisfaction of their educational experience when compared to the traditional orthopedics rotation. All SC residents successfully completed their sports medicine rotation, had completed postrotation evaluations by attending physicians, and had no duty hour violations while on sports medicine. In our experience, a sports medicine rotation is an effective alternative to the traditional orthopedics rotation for EM residents. PMID- 27186152 TI - Ramadan fasting is not usually associated with the risk of cardiovascular events: A systematic review and meta-analysis. AB - Over one billion Muslims worldwide fast during the month of Ramadan. Ramadan fasting brings about some changes in the daily lives of practicing Muslims, especially in their diet and sleep patterns, which are associated with the risk of cardiovascular diseases. Over the years, many original studies have made the effort to identify the possible impact of the Ramadan fast on cardiovascular diseases. This systematic review and meta-analysis is an attempt to present the summary of key findings from those articles and an appraisal of selected literature. A systematic search using keywords of ";Ramadan fasting" and ";cardiovascular diseases" was conducted in primary research article and gray literature repositories, in combination with hand searching and snow balling. Fifteen studies were finally selected for data extraction on the outcomes of stroke, myocardial infarction, and congestive heart failure. The analysis revealed that the incidence of cardiovascular events during the Ramadan fast was similar to the nonfasting period. Ramadan fast is not associated with any change in incidence of acute cardiovascular disease. PMID- 27186153 TI - The association between physical activity and overweight and obesity in a population of children at high and low altitudes in Southwestern Saudi Arabia. AB - OBJECTIVE: To assess the relationship between overweight and obesity and physical activity in Saudi children born and permanently domiciled at high and low altitudes in Southwestern Saudi Arabia. SUBJECTS AND METHODS: A cross-sectional study of 145 healthy Saudi children aged 10-15 years who were born and lived permanently at high altitude (3000-3100 m) and 154 healthy Saudi children of comparable age who were born and lived permanently at a relatively low altitude (500 m) was conducted. For each subject selected, body weight and body height were measured using an Avery beam weighing scale and a stadiometer, respectively. Body mass index (BMI) was calculated using the equation BMI = (weight [kg]/height [m(2)]). Physical activity scores were determined using International Physical Activity Questionnaire-Short Form-A. Resting radial pulse rate (beat/minutes) was determined clinically. RESULTS: Physical activity was significantly and inversely associated with overweight and obesity in boys at both high (chi(2) = 15.8, P< 0.001) and low (chi(2) = 14.7, P< 0.001) altitudes, but there was no clear trend for girls at either altitude. The lack of association between physical activity and overweight and obesity in girls was attributed to the low and homogeneous level of physical activity. CONCLUSION: Physical activity should be encouraged as a strategy for weight reduction in the overweight and the obese and the prevention of overweight and obesity in Saudi children at high and low altitudes. PMID- 27186154 TI - Proportion and determinants of tuberculosis among human immunodeficiency virus positive patients attending the antiretroviral therapy center attached to a Medical College in South India. AB - BACKGROUND: The human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) pandemic has caused a re-emergence of tuberculosis (TB). In persons infected with both HIV and TB, the lifetime risk of developing TB disease is 50 70% compared to 10% in HIV-negative individuals. India has world's 3(rd) highest HIV burden and is also one of the countries endemic for TB, so the country faces a dual epidemic of HIV and TB. OBJECTIVES: To find out the proportion and determinants of TB in HIV-positive subjects. SUBJECTS AND METHODS: This study was undertaken at the ART center from June 01, 2012, to May 31, 2013. HIV-positive subjects aged above 15 years who had been on antiretroviral therapy (ART) for more than 6 months were included in the study. Nonprobability purposive sampling was adopted. A predesigned semi-structured questionnaire was used to obtain data. RESULTS: A total of 536 HIV-positive people were interviewed, 58.8% of whom were males, 79.1% were Hindu, 61.0% had up to high school education, and 57% were unskilled laborers. About 63% were married, 40% were from the upper lower class, and 60% were from urban areas. For the majority (89.1%), the probable mode of transmission of HIV was by the heterosexual route. TB co-infection was present in 38.4% subjects. The most common form of TB was extra-pulmonary in subjects on antituberculous treatment (47.3%) and among old cases (57.6%). On bivariate analysis, 136 (42.4%) married subjects and those from rural areas were more commonly affected by TB compared to subjects who were unmarried and from urban areas with odds ratio (OR): 1.555, confidence interval (CI): 1.077-2.246 and OR: 1.523, CI: 1.061-2.185, respectively. The proportion of TB was high among subjects who lived in overcrowded houses 130 (44.2%), and who had a habit of alcohol use compared to others with OR: 1.731, CI: 1.734-2.179 and OR: 1.524, CI: 1.045-2.223, respectively. Logistic regression analysis showed that TB among people living with HIV/AIDS was highest in persons living in overcrowded houses (OR: 1.706, CI: 1.185-2.458) and those who consumed alcohol (OR: 1.605, CI: 1.090 2.362). CONCLUSIONS: Demographic factors like male gender, middle age, living in the rural areas, consumption of alcohol, and living in overcrowded houses were found with a higher proportion of TB. The use of highly active ART appeared to progressively decrease but did not completely eliminate the risk of TB. PMID- 27186155 TI - Can the management of blood sugar levels in gestational diabetes mellitus cases be an indicator of maternal and fetal outcomes? The results of a prospective cohort study from India. AB - BACKGROUND: Gestational diabetes mellitus (GDM) is emerging as an important public health problem in India owing to its increasing prevalence since the last decade. The issue addressed in the study was whether the management of blood sugar levels in GDM cases can predict maternal and fetal outcomes. MATERIALS AND METHODS: A prospective cohort study was done for 1 year from October 1, 2013, to September 31, 2014, at 652 diabetic screening units as a part of the Gestational Diabetes Prevention and Control Project approved by the Indian Government in the district of Kanpur, state of Uttar Pradesh. A total of 57,108 pregnant women were screened during their 24-28(th) weeks of pregnancy by impaired oral glucose test. All types of maternal and perinatal outcomes were followed up in both GDM and non GDM categories in the 2(nd) year (2013-2014) after blood sugar levels were controlled. RESULTS: It was seen that for all kinds of maternal and fetal outcomes, the differences between GDM cases and non-GDM cases were highly significant (P < 0.0001, relative risk >1 in every case). Moreover, perinatal mortality also increased significantly from 5.7% to 8.9% when blood sugar levels increased from 199 mg/dl and above. Perinatal and maternal outcomes in GDM cases were also significantly related to the control of blood sugar levels (P < 0.0001). CONCLUSION: Blood sugar levels can be an indicator of maternal and perinatal morbidity and mortality in GDM cases, provided unified diagnostic criteria are used by Indian laboratories. However, to get an accurate picture on this issue, all factors need further study. PMID- 27186156 TI - Gender inequality in acute coronary syndrome patients at Omdurman Teaching Hospital, Sudan. AB - BACKGROUND: Gender differences among patients with the acute coronary syndrome is still being debated, no research has been done on gender inequality among coronary syndrome patients in Sudan. OBJECTIVES: To study gender differences in presentation, management, and outcomes of acute coronary syndrome in Sudan. SUBJECTS AND METHODS: This cross-sectional descriptive longitudinal study was conducted in Omdurman Teaching Hospital between July 2014 and August 2015. Patients were invited to sign a written informed consent form, were interviewed and examined by a physician, and then followed during their hospital stay. Information collected includes coronary risk factors, vital signs, echocardiography findings, arrhythmias, heart failure, cardiogenic shock, and death. The Ethical Committee of Omdurman Teaching Hospital approved the research. RESULTS: A total of 197 consecutive acute coronary syndrome patients were included, 43.1% were females. A significant statistical difference was evident between males and females regarding the type of acute coronary syndrome, its presentation, and time of presentation to the hospital, smoking, and receipt of thrombolysis (P < 0.05). No differences were found with regard to age, hypertension, diabetes, family history of myocardial infarction, percutaneous coronary intervention, and in-hospital acute coronary complications (P > 0.05). CONCLUSION: Women were less likely to receive thrombolytic therapy, present with chest pain, and diagnosed with ST-segment elevation myocardial infarction. No gender differences were found in acute coronary syndrome risk factors apart from smoking, which was more common in males, and there were no differences between males and females as regards in-hospital complications. PMID- 27186158 TI - Preconception care in Saudi women with diabetes mellitus. AB - BACKGROUND: The rate of preexisting diabetes mellitus (DM) in Saudi Arabia is one of the highest in the world. The role of preconception care (PCC) is well established as a means of improving pregnancy outcomes in DM. OBJECTIVES: To assess the rate of preconception counseling, the level of PCC knowledge, and the rate of unplanned pregnancies in Saudi women with DM. MATERIALS AND METHODS: A cross-sectional study was conducted among 355 Saudi women aged 18-49 years with self-reported DM. The study questionnaire contained variables about the provision of preconception counseling, knowledge of PCC facts, and the number of unplanned pregnancies after developing DM. The level of PCC knowledge was evaluated using a modified Likert scale. Statistical Package for Social Sciences 20 was used for statistical analysis. Descriptive statistics, mean and standard deviation, and percentages were calculated; t-test was used for statistical significance. RESULTS: About one-third of the participants had received preconception counseling after being diagnosed with DM. Counseling on PCC for older and married participants was significantly less. Of the 355 participants, 42.8% had little or no PCC knowledge. All pregnancies that occurred after developing DM were unplanned. CONCLUSIONS: The rate of preconception counseling, the level of PCC knowledge in the studied Saudi women with DM is suboptimal, and none of the pregnancies that occurred after developing DM was planned. The study highlights the need for PCC programs that target all Saudi women of child-bearing age with DM, and their families starting at the age of puberty and at diagnosis of type 2DM, to optimize women's health and improve pregnancy outcomes. PMID- 27186159 TI - The unexpected truth about dates and hypoglycemia. AB - BACKGROUND: Dates are a concentrated source of essential nutrients, vitamins, minerals, and carbohydrates (CHOs), which are necessary for the maintenance of optimum health. Most of the CHOs in dates come from sugars including glucose and fructose. Dates are commonly consumed in Saudi Arabia, particularly at the time of breaking the fast to provide instant energy and maintain blood sugar level. However, dates may cause hypoglycemia in a rare condition named as heredity fructose intolerance (HFI), and a few families have been to see us with a history of that nature. This is to report the preliminary results of an on-going study of a group of patients who get symptoms of hypoglycemia following the ingestion of dates and have suffered for years without an accurate diagnosis. METHODOLOGY: This report is based on three patients, from the same family, living in a date growing region of the Kingdom of Saudi Arabia (KSA). The patients had been to several medical centers without getting any definite answers or diagnosis until they were referred to the Gastroenterology Clinic of King Fahd Hospital of the University, Al-Khobar, KSA. The data were obtained by careful history and laboratory investigations, and a final diagnosis of HFI made on fructose intolerance test (FIT). RESULTS: The patients reported that they had avoided eating dates because of various symptoms, such as bloating, nausea, and even hypoglycemia when larger amounts were consumed. Their other symptoms included sleepiness, sweating, and shivering. After full examinations and necessary laboratory tests based on the above symptoms, FIT was performed and the patients were diagnosed with HFI. They were referred to a dietitian who advised a fructose free diet. They felt well and were free of symptoms. CONCLUSION: HFI may remain undiagnosed until adulthood and may lead to disastrous complications and even death. The diagnosis can only be suspected after a careful dietary history is taken supported by FIT. This can prevent serious complications. Restricting dietary fructose may give relief from symptoms in a high proportion of patients with this disorder. PMID- 27186157 TI - Seroprevalence of erythrovirus B19 in Saudi pregnant women. AB - BACKGROUND: Erythrovirus B19 infection is associated with clinical symptoms that range from mild to severe. The common clinical presentation of B19 virus (B19V) infection is erythema infectiosum, arthropathy, aplastic crisis, and fetal infection. Infection in seronegative pregnant women can lead to fetal hydrops. OBJECTIVES: To determine the seroprevalence of immunoglobulin G (IgG) to erythrovirus B19 in Saudi pregnant women in the cities of Makkah and Jeddah in Saudi Arabia. MATERIALS AND METHODS: A total of 364 blood (serum) samples were tested for erythrovirus B19-specific-IgG antibody in Saudi pregnant women in the cities of Makkah and Jeddah in Saudi Arabia. RESULTS: Erythrovirus B19-specific IgG antibodies were detected in 182/364 (50%) of Saudi pregnant women of different age groups. CONCLUSION: This study indicated that B19V is clearly circulating in the community in a way that is similar to what is found in most nontemperate countries. PMID- 27186161 TI - Author's Reply. PMID- 27186160 TI - Vitamin D for infants. PMID- 27186162 TI - Esophageal eosinophilia in secondary adrenal insufficiency. PMID- 27186163 TI - Erratum: Control of type 2 diabetes in King Abdulaziz Housing City (Iskan) population, Saudi Arabia. AB - [This corrects the article on p. 1 in vol. 23, PMID: 26929722.]. PMID- 27186165 TI - Retraction: Non-specific Immune Response of Rainbow Trout (Oncorhynchus Mykiss) by Dietary Heat-inactivated Potential Probiotics. Immune Network 2008;8(3):67-74. PMID- 27186164 TI - Identification of brain-enriched proteins in the cerebrospinal fluid proteome by LC-MS/MS profiling and mining of the Human Protein Atlas. AB - BACKGROUND: Cerebrospinal fluid (CSF) is a proximal fluid which communicates closely with brain tissue, contains numerous brain-derived proteins and thus represents a promising fluid for discovery of biomarkers of central nervous system (CNS) diseases. The main purpose of this study was to generate an extensive CSF proteome and define brain-related proteins identified in CSF, suitable for development of diagnostic assays. METHODS: Six non-pathological CSF samples from three female and three male individuals were selected for CSF analysis. Samples were first subjected to strong cation exchange chromatography, followed by LC-MS/MS analysis. Secreted and membrane-bound proteins enriched in the brain tissues were retrieved from the Human Protein Atlas. RESULTS: In total, 2615 proteins were identified in the CSF. The number of proteins identified per individual sample ranged from 1109 to 1421, with inter-individual variability between six samples of 21 %. Based on the Human Protein Atlas, 78 brain-specific proteins found in CSF samples were proposed as a signature of brain-enriched proteins in CSF. CONCLUSION: A combination of Human Protein Atlas database and experimental search of proteins in specific body fluid can be applied as an initial step in search for disease biomarkers specific for a particular tissue. This signature may be of significant interest for development of novel diagnostics of CNS diseases and identification of drug targets. PMID- 27186166 TI - Effects of metformin and sitagliptin on glycolipid metabolism in type 2 diabetic rats on different diets. AB - INTRODUCTION: The aim of the study was to investigate the effects of metformin and sitagliptin on glycolipid metabolism in type 2 diabetes after different diets. MATERIAL AND METHODS: Seventy Male Sprague Dawley rats were fed with a high fat diet followed by streptozotocin treatment to induce type 2 diabetes. Then all rats were randomly divided into a control group, a metformin group (200 mg/kg), and a sitagliptin group (10 mg/kg). Each group was further divided into 4 groups receiving one load of high carbohydrate diet (45% glucose, 4.5 ml/kg), high fat diet (20% lipid emulsion, 4.5 ml/kg), high protein diet (20% whey protein, 10 ml/kg) or mixed meal, respectively. The caloric densities were all 33 kJ/kg. Postprandial blood glucose (P2BG), triglyceride (TG), glucagon-like peptide-1 (GLP-1), glucagon and insulin levels were measured. RESULTS: In the high carbohydrate group, sitagliptin was more efficient in lowering P2BG compared with metformin (p < 0.05). In the high-fat group, metformin was more powerful in lowering TG (p < 0.05) and P2BG (p < 0.05) levels because of its improvement of insulin sensitivity. In the high protein diet group, metformin did not reduce the P2BG level (p > 0.05), although it did reduce the TG level (p < 0.05). In the mixed diet group, metformin was more efficient in lowering P2BG (p < 0.05) but had a similar effect on TG (p > 0.05) compared with sitagliptin. CONCLUSIONS: In the type 2 diabetic model, metformin and sitagliptin have different effects on glycolipid metabolism after different diets. If it is proved in type 2 diabetic patients, then different medicines may be recommended according to different diets in order to improve glycolipid metabolism. PMID- 27186168 TI - Remote effect of kidney ischemia-reperfusion injury on pancreas: role of oxidative stress and mitochondrial apoptosis. AB - INTRODUCTION: Recent studies have demonstrated remote effects of renal ischemia/reperfusion (IR) injury on some organs such as brain, liver, and lungs. Oxidative stress is reported to be the cornerstone in such ischemic conditions. Associated apoptosis is also reported in remote lung, liver and myocardial injury after acute kidney injury. So, we postulated that renal IR may affect the pancreas by its remote effect. Oxidative stress and mitochondrial mediated apoptosis may play a crucial role in this injury. We investigated the effects of kidney IR on pancreatic exocrine and endocrine functions, antioxidant enzyme activity, and apoptosis. MATERIAL AND METHODS: The protective effect of vitamin C was also investigated. The animals were submitted to non-traumatic bilateral renal IR, sham operation or treatment with vitamin C after IR. Rats were sacrificed on the 1(st), 3(rd), and 7(th) days of the experiment to evaluate the parameters of oxidative stress (catalase, lipid peroxidase, reduced glutathione and superoxide dismutase), pancreatic endocrine and exocrine function (amylase, insulin and fasting blood glucose), renal functions (serum creatinine and blood urea nitrogen), cellular injury and apoptotic markers (Bcl-2, Bax and caspase-3). RESULTS: Kidney I/R significantly increased the renal and pancreatic functions at 1, 3 and 7 days, while fasting insulin was significantly increased at day 3 after ischemia. Moreover, I/R significantly increased the studied oxidative stress markers and decreased the antioxidant capacity in pancreatic tissues. In addition, renal I/R induced numerous histopatological lesions in pancreatic tissues and increased the apoptosis-related genes. Treating the rats with vitamin C (100 mg/kg) significantly restored the renal and pancreatic functions, improved the pancreatic antioxidant capacity and protected the pancreatic tissues from apoptotic necrosis. CONCLUSIONS: The results suggested that bilateral renal ischemia for 45 min caused significant impairment of pancreatic function and structure as indicators of acute pancreatitis. While IR enhances oxidative stress and apoptosis, vitamin C appears to play a cytoprotective role. PMID- 27186167 TI - Morphofunctional renal alterations in rats induced by intrauterine hyperglycemic environment. AB - INTRODUCTION: The renal development of rats begins in intrauterine life, finishing by 15 days after birth. Diabetes and other diseases during pregnancy can cause systemic changes in the offspring. We evaluated the structural and functional renal alterations of the offspring from diabetic mothers. MATERIAL AND METHODS: Pregnant rats were separated and 1, 7, 30 and 90 days-old (DO) pups were divided into groups according to the treatment that the mothers received: G1: control, G2: untreated diabetic and G3: insulin-treated diabetic. The kidneys from offspring at 1, 7 and 30 DO were removed for immunohistochemical and histological studies. Furthermore, blood and urine samples were collected from animals at 30 DO to determine the glomerular filtration rate (GFR) by creatinine clearance, and the animals at 90 DO were subjected to blood pressure measurement by plethysmography. RESULTS: Our results show an increase of PCNA(+) glomerular cells at 7 DO and a reduction in 30 DO animals as well as increased alpha-smooth muscle actin (alpha-SMA) tubulointerstitial expression at 1 and 7 DO in animals from G2, when compared with controls. The adult offspring from G2 showed reduced GFR and increased blood pressure. CONCLUSIONS: Maternal diabetes may have induced programming of renal damage in offspring of hyperglycemic mothers, which may have contributed to the impairment of renal function. PMID- 27186169 TI - Mutations in NEBL encoding the cardiac Z-disk protein nebulette are associated with various cardiomyopathies. AB - INTRODUCTION: Transgenic mice overexpressing mutated NEBL, encoding the cardiac specific Z-disk protein nebulette, develop severe cardiac phenotypes. Since cardiomyopathies are commonly familial and because mutations in a single gene may result in variable phenotypes, we tested the hypothesis that NEBL mutations are associated with cardiomyopathy. MATERIAL AND METHODS: We analyzed 389 patients, including cohorts of patients with dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), and left ventricular non-compaction cardiomyopathy (LVNC). The 28 coding exons of the NEBL gene were sequenced. Further bioinformatic analysis was used to distinguish variants. RESULTS: In total, we identified six very rare heterozygous missense mutations in NEBL in 7 different patients (frequency 1.8%) in highly conserved codons. The mutations were not detectable in 320 Caucasian sex-matched unrelated individuals without cardiomyopathy and 192 Caucasian sex-matched blood donors without heart disease. Known cardiomyopathy genes were excluded in these patients. The mutations p.H171R and p.I652L were found in 2 HCM patients. Further, p.Q581R and p.S747L were detected in 2 DCM patients, while the mutation p.A175T was identified independently in two unrelated patients with DCM. One LVNC patient carried the mutation p.P916L. All HCM and DCM related mutations were located in the nebulin-like repeats, domains responsible for actin binding. Interestingly, the mutation associated with LVNC was located in the C-terminal serine-rich linker region. CONCLUSIONS: Our data suggest that NEBL mutations may cause various cardiomyopathies. We herein describe the first NEBL mutations in HCM and LVNC. Our findings underline the notion that the cardiomyopathies are true allelic diseases. PMID- 27186170 TI - Impact of I/D polymorphism of ACE gene on risk of development and course of chronic obstructive pulmonary disease. AB - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) affects more than 10% of the world's population over 40 years of age. The main exogenous risk factor is cigarette smoking; however, only 20% of smokers develop COPD, indicating that some other factors, e.g. genetic, may play an important role in the disease pathogenesis. Recent research indicates that ACE (angiotensin-converting enzyme) may be a susceptibility gene for asthma or COPD. The aim of our study was to determine the influence of I/D (insertion/deletion) polymorphism of the ACE gene (AluYa5, rs4646994) on the risk and course of COPD. MATERIAL AND METHODS: We investigated ACE I/D polymorphism in 206 COPD and 165 healthy Caucasian subjects. RESULTS: In the generalized linear model (GLZ) analysis of the influence of selected factors on presence of COPD we found a significant independent effect for male sex (repeatedly increases the risk of COPD, OR = 7.7, p = 0.049), as well as smoking or lower body mass index, but only in combination with older age (OR = 0.96, p = 0.003 and OR = 1.005, p = 0.04 respectively). Interestingly, analysis of factors which may influence the risk of a higher number of exacerbations demonstrated that occurrence of DD genotype, but only in men, is associated with a lower risk (OR = 0.7, p = 0.03) of this complication. CONCLUSIONS: We suggest that ACE may not be a susceptibility gene for the origin of COPD but a disease-modifying gene. Since the impact of I/D polymorphism of the ACE gene on COPD risk is moderate or negligible, other molecular changes, that will help predict the development of this disease, should still be sought. PMID- 27186172 TI - Indirect costs of inflammatory bowel diseases: Crohn's disease and ulcerative colitis. A systematic review. AB - INTRODUCTION: Crohn's disease and ulcerative colitis are lifelong illnesses which have a significant impact on quality of life and personal burden through a reduction in the ability to work, sick leave and restrictions of leisure time. The aim of this study was to conduct a systematic review of the indirect costs of Crohn's disease and ulcerative colitis. MATERIAL AND METHODS: The search was carried out in Medline, EMBASE, the Centre for Reviews and Dissemination, and reference lists of identified articles and reference lists of identified articles were also handsearched. All costs were adjusted to 2013 USD values by using the consumer price index and purchasing power parity. Identified studies were then analysed in order to assess their heterogeneity and possibility of inclusion in the meta-analysis. RESULTS: Eleven of the identified publications presented indirect costs of Crohn's disease or ulcerative colitis. The range of estimated yearly indirect costs per patient was large, from $1 159.09 for loss of earnings to $14 135.64 for lost productivity and sick leave for Crohn's disease. The values for ulcerative colitis ranged from $926.49 to $6 583.17. Because of the imprecise definition of methods of indirect cost calculations as well as heterogeneity of indirect cost components, a meta-analysis was not performed. CONCLUSIONS: The indirect costs of ulcerative colitis seem to be slightly lower than in the case of Crohn's disease. A small number of studies referring to indirect costs of Crohn's disease and ulcerative colitis were identified, which indicates the need to conduct further investigations on this problem. PMID- 27186171 TI - Association analysis of the COL1A1 polymorphism with bone mineral density and prevalent fractures in Polish postmenopausal women with osteoporosis. AB - INTRODUCTION: Polymorphism in the promoter region of collagen type 1alpha (COL1A1) +1245G/T (Sp1, rs1800012) was in some studies shown to be relevant for bone mineral density (BMD) and low-energy fracture prediction. The aim of the study was to confirm this finding in a group of postmenopausal women diagnosed with osteoporosis. MATERIAL AND METHODS: We investigated 311 Caucasian women (mean age: 65.2 +/-9.39 years) either after low-energy fractures (regardless of the location) or meeting World Health Organization (WHO) criteria for osteoporosis. All patients underwent clinical examination in order to exclude secondary osteoporosis; hip and lumbar spine DEXA was performed (Lunar). The three genotypes of Sp1 polymorphism were determined by RFLP (restriction fragment length polymorphism). RESULTS: Distribution of COL1A1 genotypes (SS/Ss/ss) agreed with Hardy-Weinberg equilibrium. No relation between COL1A1 genotypes and hip/L1 L4 BMD was found. Fractures were reported in 26.3% of women. Prevalence of low energy fractures, regardless of the type, was 50.0% in ss genotype carriers, 26.4% in SS homozygotes and 23.7% in Ss heterozygotes. There was no statistically significant recessive or dominant effect of any Sp1 genotype on fracture prevalence (p = 0.613). CONCLUSIONS: We failed to observe that COL1A1 Sp 1 genotypes contribute to BMD determination or are associated with prevalent low energy fractures in a Polish cohort of postmenopausal osteoporotic women. PMID- 27186173 TI - The association of clinical indication for exercise stress testing with all-cause mortality: the FIT Project. AB - INTRODUCTION: We hypothesized that the indication for stress testing provided by the referring physician would be an independent predictor of all-cause mortality. MATERIAL AND METHODS: We studied 48,914 patients from The Henry Ford Exercise Testing Project (The FIT Project) without known congestive heart failure who were referred for a clinical treadmill stress test and followed for 11 +/-4.7 years. The reason for stress test referral was abstracted from the clinical test order, and should be considered the primary concerning symptom or indication as stated by the ordering clinician. Hierarchical multivariable Cox proportional hazards regression was performed, after controlling for potential confounders including demographics, risk factors, and medication use as well as additional adjustment for exercise capacity in the final model. RESULTS: A total of 67% of the patients were referred for chest pain, 12% for shortness of breath (SOB), 4% for palpitations, 3% for pre-operative evaluation, 6% for abnormal prior testing, and 7% for risk factors only. There were 6,211 total deaths during follow-up. Compared to chest pain, those referred for palpitations (HR = 0.72, 95% CI: 0.60 0.86) and risk factors only (HR = 0.72, 95% CI: 0.63-0.82) had a lower risk of all-cause mortality, whereas those referred for SOB (HR = 1.15, 95% CI: 1.07 1.23) and pre-operative evaluation (HR = 2.11, 95% CI: 1.94-2.30) had an increased risk. In subgroup analysis, referral for palpitations was protective only in those without coronary artery disease (CAD) (HR = 0.75, 95% CI: 0.62 0.90), while SOB increased mortality risk only in those with established CAD (HR = 1.25, 95% CI: 1.10-1.44). CONCLUSIONS: The indication for stress testing is an independent predictor of mortality, showing an interaction with CAD status. Importantly, SOB may be associated with higher mortality risk than chest pain, particularly in patients with CAD. PMID- 27186174 TI - The diagnostic value of supine blood pressure in hypertension. AB - INTRODUCTION: Correct blood pressure (BP) measurement is crucial in the diagnosis of arterial hypertension (AH), and controversy exists whether supine BP should be treated as equal to sitting BP. The aim of this study was to evaluate the relation of supine BP to sitting BP and ambulatory BP with regard to identification of diagnostic cut-offs for hypertension. MATERIAL AND METHODS: This study included 280 patients with AH (mean age: 44.3 +/-10.6 years). The following measurements of BP were performed and analyzed: 1) sitting office blood pressure measurement (OSBP and ODBP); 2) supine BP (supSBP and supDBP), measured automatically (5 times with a 2-minute interval) during evaluation by the Niccomo device (Medis, Germany); 3) 24-hour ambulatory blood pressure (ABP) monitoring. RESULTS: The mean supSBP and supDBP were found to be lower than OSBP and ODBP (130.9 +/-14.2 vs. 136.6 +/-15.5 mm Hg and 84.8 +/-9.4 vs. 87.8 +/-10.2 mm Hg, respectively; p < 0.000001). The correlations between ABP and supBP/OBP were moderate and strong (correlation coefficients in range 0.55-0.76). The ROC analysis revealed that mean supBP >= 130/80 mm Hg was more precise than OBP >= 140/90 mm Hg in diagnosing hypertension (AUC: 0.820 vs. 0.550; sensitivity 80.7% vs. 57.4%; specificity 83.2% vs. 52.7%; p < 0.0001) and the additive value derived mostly from its higher predictive power of identifying patients with increased night-time BP. CONCLUSIONS: In young and middle-aged hypertensive patients the blood pressure during a 10-minute supine rest was lower than in the sitting position. The supine blood pressure >= 130/80 mm Hg was found to be a specific and sensitive threshold for hypertension. PMID- 27186175 TI - Red cell distribution width and end-organ damage in patients with systo-diastolic hypertension. AB - INTRODUCTION: Both end-organ damage and high red cell distribution width (RDW) values are associated with adverse cardiovascular events, inflammatory status, and neurohumoral activation in hypertensive disease and in the general population. In this study, we investigated the relationship between RDW and end organ damage in hypertensive patients. MATERIAL AND METHODS: The 446 systo diastolic hypertensive patients included in the study received 24-hour ambulatory blood pressure monitoring. Left ventricular mass index, glomerular filtration rate, and microalbuminuria were measured to identify end-organ damage. High sensitivity C-reactive protein (hs-CRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels of all patients were also examined. RESULTS: The mean age of the participants was 49.96 +/-11.04 years. The mean RDW was 13.06 +/ 1.05%. Red cell distribution width was positively correlated with left ventricular myocardial index (LVMI), urinary albumin, hs-CRP, and NT-proBNP (r = 0.298, p < 0.001; r = 0.228, p < 0.001; r = 0.337, p < 0.001; r = 0.277, p < 0.001, respectively), while RDW was negatively correlated with eGFR (r = -0.153, p < 0.001). Additionally, while there was a positive correlation between RDW and 24-h systolic blood pressure, no correlation was found between RDW and 24-h diastolic blood pressure (r = 0.132, p = 0.006 and r = 0.017, p = 0.725, respectively). Multiple linear regression analysis revealed that RDW levels were independently associated with eGFR, LVMI, and severity of albuminuria (beta = 0.126, p = 0.010; beta = -0.149, p = 0.002; beta = 0.114, p = 0.035). CONCLUSIONS: High RDW levels in systo-diastolic hypertensive patients were found to be an independent predictor of end-organ damage. PMID- 27186176 TI - Quality of life in patients with coronary heart disease after myocardial infarction and with ischemic heart failure. AB - INTRODUCTION: Quality of life measures are useful when interventions or treatments are indicated for several reasons such as improvement of physical functioning, pain relief, to estimate the effectiveness of therapies or to predict mortality. The aim of the current study was to describe quality of life in patients with stable coronary artery disease, myocardial infarction and heart failure and to evaluate the relationship between depression and health-related quality of life. MATERIAL AND METHODS: Patients after STEMI, with stable coronary artery disease, and heart failure (n = 332) completed the MacNew Heart Disease Health-related Quality of Life Questionnaire and the Hospital Anxiety and Depression Scale. RESULTS: Patients with myocardial infarction had significantly higher scores than patients with stable coronary artery disease or heart failure on the MacNew global scale (p < 0.001) and the physical (p < 0.001), emotional (p < 0.001) and social (p < 0.001) subscales. The anxiety scores were significantly higher in the group of patients with stable coronary artery disease than in patients with myocardial infarction (p < 0.05). The depression scores were significantly higher in patients with heart failure (p < 0.01). CONCLUSIONS: In patients with stable CAD, anxiety correlated mainly with symptoms, i.e. angina, than with the history of MI. Patients with symptoms of angina react to the illness with anxiety more than depression, whereas patients with heart failure with dyspnea react to the illness with depressive symptoms more than anxiety. In patients after MI and with stable CAD, cognitive-behavioral techniques could be useful to quickly reduce the level of anxiety, while patients with heart failure require long-term support therapy to reduce the risk of depressive symptoms. PMID- 27186177 TI - Correlation between B type natriuretic peptide and metabolic risk factors. AB - INTRODUCTION: It has been shown that B type natriuretic peptide (BNP) level can indicate cardiovascular disease. However, the association between BNP and metabolic risk factors is unknown. The aim of this study was to investigate the correlation between N-terminal pro-B type natriuretic peptide (NT-proBNP) and metabolic risk factors. MATERIAL AND METHODS: A total of 11,508 subjects were selected from those who underwent health examinations in our hospital. NT-proBNP, waist circumference, blood pressure, fasting plasma glucose and lipid profile were measured. The level of NT-proBNP was measured and classified into four stratifications (BNP >= 20 pg/ml, >= 40 pg/ml, >= 60 pg/ml, and >= 80 pg/ml) to analyze the relationship between BNP and metabolic risk factors. RESULTS: B type natriuretic peptide increased gradually with increasing age (p < 0.001). The BNP levels were significantly higher in women than in men (p < 0.001). Multivariate regression analysis showed a positive association between NT-proBNP levels and systolic blood pressure (p < 0.001), fasting plasma glucose (p < 0.05), and total cholesterol (p < 0.001 in women). The NT-proBNP levels were inversely associated with diastolic blood pressure, waist circumference, triglyceride, high-density lipoprotein, and LDL cholesterol. Logistic regression analysis demonstrated a close relationship between NT-proBNP and systolic blood pressure, fasting plasma glucose, and total cholesterol. In the BNP >= 60 pg/ml group, odds ratio (OR) values were 1.80, 1.56 and 1.54 (female) and 3.74, 1.59 and 1.51 (male), respectively. In the BNP >= 80 pg/ml group, OR values were 2.45, 1.65 and 1.84 (female) and 4.61, 1.66 and 1.75 (male), respectively. CONCLUSIONS: NT-proBNP was independently associated with the main metabolic risk factors (systolic blood pressure, fasting plasma glucose, and total cholesterol). These findings suggest that the combined determination of NT-proBNP and the main metabolic risk factors could be important in assessing cardiovascular morbidity. PMID- 27186178 TI - Plasma B-type natriuretic peptide levels are poorly related to the occurrence of ischemia or ventricular arrhythmias during symptom-limited exercise in low-risk patients. AB - INTRODUCTION: The usefulness of B-type natriuretic peptide (BNP) as a marker of ischemia is controversial. BNP levels have predicted arrhythmias in various settings, but it is unknown whether they are related to exercise-induced ischemic ventricular arrhythmias. MATERIAL AND METHODS: We analyzed in 63 patients (64 +/ 14 years, 65% male, 62% with known coronary disease) undergoing exercise stress single-photon emission computed tomography (SPECT) the association between plasma BNP values (before and 15 min after exercise) and the occurrence of ischemia or ventricular arrhythmias during the test. RESULTS: Exercise test (8.1 +/-2.7 min, 7.4 +/-8.1 metabolic equivalents, 82 +/-12% of maximal predicted heart rate) induced reversible perfusion defects in 23 (36%) patients. Eight (13%) patients presented significant arrhythmias (>= 7 ventricular premature complexes/min, couplets, or non-sustained ventricular tachycardia during exercise or in the first minute of recovery). Median baseline BNP levels were 17.5 (12.4-66.4) pg/ml in patients developing scintigraphic ischemia and 45.6 (13.2-107.4) pg/ml in those without ischemia (p = 0.137). The BNP levels increased after exercise (34.4 (15.3-65.4)% increment over baseline, p < 0.001), but the magnitude of this increase was not related to SPECT positivity (35.7 (18.8-65.4)% vs. 27.9 (5.6 64.0)% in patients with and without ischemia, respectively, p = 0.304). No significant association was found between BNP values (at baseline or their change during the test) and ventricular arrhythmias. CONCLUSIONS: Plasma BNP values - at baseline or after exercise - were not associated with myocardial ischemia or with ventricular arrhythmia during exercise SPECT. These results highlight the limited usefulness of this biomarker to assess acute ischemia. PMID- 27186179 TI - Impact of septal flash and left ventricle contractile reserve on positive remodeling during 1 year cardiac resynchronization therapy: the multicenter ViaCRT study. AB - INTRODUCTION: Cardiac resynchronization therapy (CRT) has been shown to improve outcomes in patients with systolic heart failure (HFREF). However, the relatively high non-responder rate results in a need for more precise qualification for CRT. The ViaCRT study was designed to determine the role of contractile reserve and dyssynchrony parameters in predicting CRT response. The purpose of this analysis was to determine the effect of baseline septal flash and contractile reserve (CR) on clinical and echocardiographic parameters of response to CRT in 12-month follow-up. MATERIAL AND METHODS: One hundred thirty-three guideline-selected CRT candidates (both ischemic and non-ischemic heart failure with reduced ejection fraction) were enrolled in the study. Baseline study population characteristics were: left ventricle ejection fraction (LVEF) 25 +/-6%, QRS 165 +/-25 ms, NYHA class III (90%) and IV (10%). RESULTS: In subjects with septal flash (SF) registered before CRT implantation improvement in LVEF (14 +/-2% vs. 8 +/-1%, p < 0.05) and left ventricle (LV) systolic (63 +/-10 ml vs. 36 +/-6 ml, p < 0.05) and diastolic (46 +/-10 ml vs. 32 +/-7, p < 0.05) volumes was more pronounced than in patients without SF. In patients with CR (defined as LVEF increase by 20% or 4 viable segments) improvement in echo parameters was not significantly different then in the CR- group. Neither SF nor CR was associated with improvement in NYHA class. Subgroup analysis revealed that only in non-ischemic HF patients is presence of septal flash associated with LV function improvement after CRT. CONCLUSIONS: In non-ischemic HF patients septal flash is a helpful parameter in prediction of LV remodeling after 12 months of resynchronization therapy. PMID- 27186180 TI - Comparison of results of endovascular stenting and bypass grafting for TransAtlantic Inter-Society (TASC II) type B, C and D iliac occlusive disease. AB - INTRODUCTION: The priority use of endovascular techniques in the management of aortoiliac occlusive disease has increased in the last decade. The aim of the present article is to report 1- and 2-year results of iliac artery stenting (IAS) and aortoiliac grafting in the management of patients with TASC II type B, C and D iliac lesions and chronic limb ischaemia. MATERIAL AND METHODS: In this prospective, non-randomised, one-centre clinical study, iliac artery stents and vascular grafts used for the treatment of patients with symptomatic lesions in the iliac artery were evaluated. This study enrolled 2 groups: 54 patients in the stent group and 47 patient in the surgery group. RESULTS: The primary patency rates at 1 and 2 years were 83% and 79.9% after IAS and 97.1% and 97.1% after surgical reconstruction, respectively (p = 0.015). The assisted primary stent patency at 1 and 2 years was 87.9% and 78.2%, respectively. The complication rate was 7.4% in the stent group and 6.3% in the surgery group. There was no perioperative mortality in either group. CONCLUSIONS: Our results reveal that patients with severe aortoiliac occlusive disease (TASC II types B, C and D) can be treated with IAS or surgically with satisfactory results. Iliac artery stenting is associated with decreased primary patency compared with the surgery group. Iliac artery stenting should be considered with priority in elderly patients or in patients with severe comorbidities. PMID- 27186181 TI - Analysis of adverse events of sunitinib in patients treated for advanced renal cell carcinoma. AB - INTRODUCTION: Treatment of the metastatic stage of renal cell carcinoma is specific because classical chemotherapy is not applicable here. The treatment is mainly based on molecularly targeted drugs, including inhibitors of tyrosine kinases. In many cases the therapy takes many months, and patients often report to general practitioners due to adverse events. In this article, the effectiveness and side effects of one of these drugs are presented. The aim of the study was to analyse of the toxicity and safety of treatment with sunitinib malate in patients with clear cell renal cell carcinoma in the metastatic stage. MATERIAL AND METHODS: Adverse events were analyzed using retrospective analysis of data collected in a group of 39 patients treated in the Department of Systemic and Generalized Malignancies in the Cancer Center in Krakow, Poland. RESULTS: Toxicity of treatment affected 50% of patients. The most common side effects observed were hypertension, thrombocytopenia, stomatitis, diarrhea and weakness. Grade 3 serious adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) version 4 affected up to 10% of patients. The most common serious adverse events were hypertension and fatigue. CONCLUSIONS: Sunitinib malate is characterized by a particular type of toxicity. Knowledge of the types and range of adverse events of this drug is an important part of oncological and internal medicine care. PMID- 27186182 TI - Esophageal capsule endoscopy is not the optimal technique to determine the need for primary prophylaxis in patients with cirrhosis. AB - INTRODUCTION: Capsule endoscopy has been suggested as a potential alternative to endoscopy for detection of esophagogastric varices and severe portal hypertensive gastropathy (PHG). The aim of the study was to determine whether PillCam esophageal capsule endoscopy could replace endoscopy for screening purposes. MATERIAL AND METHODS: Sixty-two patients with cirrhosis with no previous variceal bleeding had PillCam capsule endoscopy and video endoscopy performed on the same day. Sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of capsule endoscopy were compared to endoscopy for the presence and severity of esophageal and gastric varices, PHG and the need for primary prophylaxis. Patients' preference was assessed by a questionnaire. RESULTS: Four (6%) patients were unable to swallow the capsule. Sensitivity, specificity, PPV and NPV of capsule endoscopy for detecting any esophageal varices (92%, 50%, 92%, 50%), large varices (55%, 91%, 75%, 80%), variceal red signs (58%, 87%, 69%, 80%), PHG (95%, 50%, 95%, 50%), and the need for primary prophylaxis (91%, 57%, 78%, 80%) were not optimal, with only moderate agreement (kappa) between capsule and upper GI endoscopy. Had only a capsule endoscopy been performed, 12 (21.4%) patients would have received inappropriate treatment. Capsule endoscopy also failed to detect (0/13) gastric varices. The majority of patients ranked capsule endoscopy as more convenient (69%) and their preferred (61%) method. CONCLUSIONS: Despite the preference expressed by patients for capsule endoscopy, we believe that upper GI endoscopy should remain the preferred screening method for primary prophylaxis. PMID- 27186183 TI - Prognostic and diagnostic value of procalcitonin in the post-transplant setting after liver transplantation. AB - INTRODUCTION: The aim of the study was to assess the diagnostic accuracy of procalcitonin (PCT) as a marker for complications and as a prognostic factor for mortality after liver transplantation. MATERIAL AND METHODS: Liver transplant patients between January 2007 and April 2011 were prospectively included in the study. Procalcitonin serum concentration was recorded before, 6 h after reperfusion and then daily. Postoperative clinical course was prospectively analyzed from admission to discharge. Main surgical data such as operating procedure, type of reperfusion, operating and ischemic times, high urgency (HU) status and MELD score at the time of transplantation were also recorded. RESULTS: Sixteen patients with initial PCT > 5 ng/ml suffered >= 1 complication (p = 0.03). However, there was no association between the level of the 1(st) peak PCT and the further postoperative course or the occurrence of complications. Patients in whom a 2(nd) PCT peak occurred had a significantly higher risk for a complicated course, for a complicated sepsis course and for mortality (p < 0.0001). Warm ischemic time over 58 min, operating time over 389 min and HU status were significant independent factors for a complicated postoperative course (p < 0.001, p < 0.001 and p = 0.03 respectively). CONCLUSIONS: Based on our results, we believe that PCT course and the occurrence of a 2(nd) peak seem to possess important diagnostic and prognostic power in the post-transplant setting after liver transplantation. PMID- 27186184 TI - Multidisciplinary rehabilitation and steroids in the management of multiple sclerosis relapses: a randomized controlled trial. AB - INTRODUCTION: Periodic relapses are one of the main characteristics of multiple sclerosis (MS), from which recovery is often incomplete despite high-dose methylprednisolone (HDMP) treatment. The aim of our study was to evaluate the potential benefits of short-term HDMP combined with multidisciplinary rehabilitation (MDR) in persons with MS in relapse in order to assess whether combination of steroid therapy with MDR is more beneficial than steroid therapy alone. MATERIAL AND METHODS: This investigation was conducted as a randomized controlled trial. The MS patients were eligible if they had an established diagnosis and relapse requiring application of HDMP. Forty-nine patients were included in the study and randomized to control and treatment groups, and 37 completed the study. High-dose methylprednisolone was administered to all patients. The treatment group additionally underwent an MDR program over a 3-week period. All outcome measures were completed at baseline and 1 and 3 months later. RESULTS: The Expanded Disability Status Scale (EDSS) and Functional Independence Measure (FIM) motor scores improved statistically significantly 1 month after HDMP, in both treatment and control groups. During the study period, in the treatment group, a sustained large effect size (ES) was found for both physical and mental composite scores of Multiple Sclerosis Quality of Life-54 (MSQoL-54), while in the controls, a sustained moderate ES was demonstrated only for physical composite score. CONCLUSIONS: Our findings suggest that MDR improves MS relapse outcome. PMID- 27186185 TI - Evaluation of sural nerve automated nerve conduction study in the diagnosis of peripheral neuropathy in patients with type 2 diabetes mellitus. AB - INTRODUCTION: New tests for improved diagnosis of diabetic peripheral neuropathy (DPN) are useful. MATERIAL AND METHODS: We evaluated the utility of automated nerve conduction study (NCS) of the sural nerve with a new portable device for the diagnosis of DPN in patients with type 2 diabetes mellitus (T2DM). This study included 114 T2DM patients (58 men) with mean age 64.60 +/-8.61 years. Exclusion criteria were B12 depletion, alcohol abuse and other causes of peripheral neuropathy. The reference method was the Neuropathy Disability Score (NDS) with a threshold NDS >= 3. Sural nerve automated NCS was carried out with the portable NC-stat DPNCheck device. Sensory nerve conduction velocity and sensory nerve action potential amplitude were measured bilaterally. Automated NCS was considered abnormal when >= 1 of the two aforementioned neurophysiological parameters was abnormal in at least one leg. RESULTS: Examination with NC-stat DPNCheck exhibited 90.48% sensitivity, 86.11% specificity, 79.17% positive predictive value (PPV) and 93.94% negative predictive value (NPV). The positive likelihood ratio (LR+) was 6.51 and the negative likelihood ratio (LR-) was 0.11. CONCLUSIONS: Sural nerve automated NCS with the NC-stat DPNCheck device exhibits high sensitivity and specificity for the diagnosis of DPN in T2DM. PMID- 27186186 TI - The impact of excessive maternal weight on the nutritional status of the fetus - the role of leptin. AB - INTRODUCTION: Assessment of leptin concentration in the blood of pregnant women (leptin concentration - Lc) and in their newborns, according to their nutritional status. MATERIAL AND METHODS: Pregnant women (n = 42) were divided into normal body mass (NBM) and excessive body mass (EBM) groups. Neonates were divided into AGA (eutrophic) and LGA (macrosomic) groups. Leptin concentraction was studied in 4 subgroups: NBM/AGA, NBM/LGA, EBM/AGA, EBM/LGA. RESULTS: Mothers: A significant correlation was found between maternal Lc and body mass index (BMI) (r = 0.75, p < 0.001). Maternal Lc was 3 times higher than neonatal Lc (p < 0.00001). The NBM mothers showed lower Lc compared to EBM mothers (p = 0.000018). Leptin concentration values in NBM/LGA and NBM/AGA mothers were similar (p = 0.6775). Newborns: Correlations were found between Lc and ponderal index (PI) (r = 0.67, p < 0.001), weight (r = 0.43, p = 0.004) and placental weight (r = 0.56, p < 0.001). Girls presented higher Lc than boys (p = 0.0338). In LGA groups, newborns born to EBM mothers presented higher Lc than those born to NBM mothers (p = 0.0013). In both AGA groups, Lc was similar (AGA/EBM vs. AGA/NBM p = 0.1619). The highest Lc and the largest placentas were found in the group of LGA newborns born to EBM mothers. CONCLUSIONS: Leptin concentration positively correlates with BMI in pregnant women, with PI and female sex in newborns as well as with placental weight. The nutritional status of fetuses does not affect the Lc of their non obese mothers. The LGA neonates born to EBM women demonstrate higher Lc than LGA neonates born to NBM mothers, whereas Lc of AGA neonates is similar regardless of the nutritional status of their mothers. PMID- 27186187 TI - Predictors of deterioration of lung function in Polish children with cystic fibrosis. AB - INTRODUCTION: Severity of lung disease varies in patients with the same CFTR genotype. It suggests that other factors affect the severity of cystic fibrosis (CF). The aim of the study was to identify risk factors that determine lung function decline in Polish cystic fibrosis children. MATERIAL AND METHODS: The follow-up time was no less than 5 years of respiratory status observation based on the forced expiratory volume in 1 s value (FEV1). The socio-economic data, perinatal interview, presence of meconium ileus (MI), time of CF diagnosis, initiation of tobramycin inhalation solution (TIS), pancreatic function, sensitization to Aspergillus fumigatus, presence of impaired glucose tolerance (IGT) or diabetes mellitus, chronic bacterial colonization and number of exacerbations and hospitalizations were assessed. RESULTS: The mean age of 61 included children was 13.3 +/-7.6 years. Delta F508 homozygosity was detected in 45.9%, 44.3% were delta F508 heterozygous, and 9.8% had other genotypes. FEV1 decline was observed among 20% of patients; the rest of the patients presented stable values of FEV1 during at least 5 years of observation. The most significant predictors related to the decline of FEV1 were presentation of MI (p = 0.0344), IGT (p = 0.0227), number of exacerbations (p = 0.0288), and early Pseudomonas aeruginosa (PA) chronic colonization (p = 0.0165) followed by late TIS initiation after the first detection of PA (p=0.0071). Neither time of diagnosis nor type of CFTR mutation was statistically significant as a predictor of lung deterioration. CONCLUSIONS: The presence of MI, IGT, chronic PA colonization, and number of exacerbations are risk factors for lung function deterioration. PMID- 27186189 TI - High prevalence of chronic hepatitis D virus infection in Eastern Turkey: urbanization of the disease. AB - INTRODUCTION: Both hepatitis B virus (HBV) and hepatitis D virus (HDV) infection play an increasingly important role in liver diseases. The main objective of this study was to investigate the socio-epidemiological, laboratory and radiological aspects of both HBV and HDV infection near the Iranian border of Turkey. MATERIAL AND METHODS: The study included 3352 patients with HBV and HDV infection. Socioepidemiological, laboratory and radiological aspects of the study subjects were retrospectively examined. Comorbid metabolic diseases were not assessed due to the retrospective design of the study. RESULTS: Most of the study subjects were HBe antigen negative. No significant difference in terms of HBV-DNA levels or HBe antigen seropositivity was detected between the city centre and rural areas (p > 0.005). The mean HBV-DNA level in the anti-HDV-positive group was significantly lower than in the anti-HDV-negative group (p < 0.001). The rate of HDV-RNA positivity in women was higher than in their male counterparts (p = 0.017). Anti-HDV-IgG was detected in 18.4% of tested subjects who came from an urban area. In contrast, 12.5% of subjects of the rural group had a positive result for anti-HDV-IgG. Among 134 ultrasonographically evaluated delta hepatitis patients, 37.3% had liver cirrhosis. On the other hand, in 1244 patients with hepatitis B monoinfection, there were 90 patients with liver cirrhosis. Radiologically, the rate of hepatic steatosis in delta hepatitis patients was lower than in those with HBV monoinfection. CONCLUSIONS: Hepatitis D virus infection was particularly prevalent among the urban population as well as in female subjects. More broadly, the current observations are the first to suggest an inverse correlation between delta hepatitis and ultrasonography-proven hepatic steatosis. PMID- 27186188 TI - Usefulness of inflammatory biomarkers in discriminating between bacterial and aseptic meningitis in hospitalized children from a population with low vaccination coverage. AB - INTRODUCTION: Neisseria meningitidis and Streptococcus pneumoniae are the most frequent pathogens responsible for meningitis beyond the neonatal period. Aseptic meningitis is a disabling condition, but bacterial meningitis if left untreated is 100% fatal. The aim of the study was to analyze the usefulness of biochemical and hematological parameters in distinguishing between bacterial and non bacterial meningitis in children with meningitis from a population with low rates of vaccination against S. pneumoniae and N. meningitidis. MATERIAL AND METHODS: This study is a retrospective chart review of children hospitalized with meningitis. In patients with aseptic and bacterial meningitis the following parameters were compared: C-reactive protein, D-dimers, fibrinogen, glucose level, and leukocyte level, and in cerebrospinal fluid, protein, glucose, and leukocyte concentrations were analyzed. Number of points in the Bacterial Meningitis Score (BMS) was calculated. The predictive value of each parameter to distinguish between bacterial and aseptic meningitis was evaluated. RESULTS: In total, 129 patients were included in the study: 65 diagnosed with bacterial meningitis and 64 with aseptic meningitis. Bacterial and aseptic meningitis were statistically significantly different based on each analyzed parameter (p < 0.000001). Among children with aseptic meningitis 42 (66%) scored 0 points in the BMS, while all the children with bacterial meningitis had at least one point. CONCLUSIONS: In children with meningitis inflammatory biomarkers differ statistically significantly depending on the etiology - bacterial or aseptic. Serum concentration of C-reactive protein higher than 80 mg/dl is a useful marker of bacterial etiology of meningitis. A high Bacterial Meningitis Score is indicative for bacterial meningitis. PMID- 27186190 TI - Five years of experience with rituximab plus high-dose dexamethasone for relapsed/refractory chronic lymphocytic leukemia. AB - INTRODUCTION: High-dose methylprednisolone (HDMP) in combination with rituximab is active in the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL), but serious infections are frequent. Recently published data suggested that high-dose dexamethasone might be equally effective as HDMP despite a lower cumulative dose. MATERIAL AND METHODS: We performed retrospective analysis of 60 patients with relapsed/refractory CLL (median age: 66 years; range: 37-86) treated with rituximab plus dexamethasone (R-dex) at a single tertiary center between September 2008 and October 2012. The schedule of R-dex consisted of rituximab 500 mg/m(2) i.v. day 1 (375 mg/m(2) in cycle 1) and dexamethasone 40 mg orally on days 1-4 and 10-13 repeated every 3 weeks for a maximum of 8 cycles. Unfavorable prognostic features were frequent (Rai stages III/IV in 67%, unmutated IgVH 82%, del 11q 43%, TP53 mutation/deletion 23%, bulky lymphadenopathy 58% of patients). RESULTS: Overall response (OR)/complete remission (CR) was achieved in 75/3%. At the median follow-up of 21 months, median progression-free survival (PFS) was 8 months, median time to next treatment 12.9 months and median overall survival 25.5 months. Refractoriness to fludarabine (p = 0.04) and age >= 65 years (p = 0.03) were significant predictors of shorter PFS. R-dex was successfully used for debulking before allogenic stem cell transplantation in 7 patients (12%). Serious (CTCAE grade III/IV) infections occurred in 27% of patients; 20% of patients developed steroid diabetes requiring temporary short-acting insulin. CONCLUSIONS: Our results show that R-dex is an active and well-tolerated regimen for patients with relapsed/refractory CLL; however, major infections remain frequent despite combined antimicrobial prophylaxis. PMID- 27186191 TI - Cardiotoxicity of anthracycline therapy: current perspectives. AB - Anthracyclines, especially doxorubicin and daunorubicin, are the drugs of first choice in the treatment of patients with hematologic malignancies, soft-tissue sarcomas, and solid tumors. Unfortunately, the use of anthracyclines is limited by their dose-dependent and cumulative cardiotoxicity. The molecular mechanism responsible for anthracycline-induced cardiotoxicity remains poorly understood, although experimental and clinical studies have shown that oxidative stress plays the main role. Hence, antioxidant agents, especially dexrazoxane, and also other drug classes (statins, beta-blockers) proved to have a beneficial effect in protecting against anthracycline-induced cardiotoxicity. According to previous clinical trials, the major high-risk factors for anthracycline-induced cardiotoxicity are age, body weight, female gender, radiotherapy, and other diseases such as Down syndrome, familial dilated cardiomyopathy, diabetes and hypertension. Consequently, further studies are needed to elucidate the molecular pathogenesis of anthracycline-induced cardiotoxicity and also to discover new cardioprotective agents against anthracycline-induced cardiotoxicity. PMID- 27186194 TI - How much does care in palliative care wards cost in Poland? AB - INTRODUCTION: The main task of palliative care units is to provide a dignified life for people with advanced progressive chronic disease through appropriate symptom management, communication between medical specialists and the patient and his family, as well as the coordination of care. Many palliative care units struggle with low incomes from the National Health Fund (NHF), which causes serious economic problems. The aim of the study was to estimate of direct and administrative costs of care and the actual cost per patient per day in selected palliative care units and comparison of the results to the valuation of the NHF. MATERIAL AND METHODS: The study of the costs of hospitalization of 175 patients was conducted prospectively in five palliative care units (PCUs). The costs directly associated with care were recorded on the specially prepared forms in each unit and also personnel and administrative costs provided by the accounting departments. RESULTS: The total costs of analyzed units amounted to 209 002 EUR (898 712 PLN), while the payment for palliative care services from the NHF amounted to 126 010 EUR (541 844 PLN), which accounted for only 60% of the costs incurred by the units. The average cost per person per day of hospitalization, calculated according to the actual duration of hospitalization in the unit, was 83 EUR (357 PLN), and the average payment from the NHF was 52.8 EUR (227 PLN). Underpayment per person per day was approximately 29.2 EUR (125 PLN). CONCLUSIONS: The study showed a significant difference between the actual cost of palliative care units and the level of refund from the NHF. Based on the analysis of costs, the application has been submitted to the NHF to change the reimbursement amount of palliative care services in 2013. PMID- 27186192 TI - The role of micronutrients in the risk of urinary tract cancer. AB - Prostate, bladder and kidney cancers remain the most common urological malignancies worldwide, and the prevention and treatment of these diseases pose a challenge to clinicians. In recent decades, many studies have been conducted to assess the association between supplementation with selected vitamins and elements and urinary tract tumour initiation and development. Here, we review the relationship between vitamins A, B, D, and E, in addition to calcium, selenium, and zinc, and the risk of developing prostate, kidney and bladder cancer. A relatively consistent body of evidence suggests that large daily doses of calcium (> 2,000 mg/day) increase the risk of prostate cancer. Similarly, supplementation with 400 IU/day of vitamin E carries a significant risk of prostate cancer. However, there have been many conflicting results regarding the effect of these nutrients on kidney and bladder neoplasms. Moreover, the role of other compounds in urinary tract carcinogenesis needs further clarification. PMID- 27186193 TI - Practical approach to management of chronic lymphocytic leukemia. AB - Revolutionary progress has recently changed the landscape of chronic lymphocytic leukemia (CLL). Powerful prognostic factors, especially p53 mutation and/or deletion and IGHV mutation status, have refined individual patient prognosis. Purine analogs and monoclonal antibodies paved the way from palliative treatment to chemoimmunotherapy capable of eradication of minimal residual disease and prolongation of survival. Obinutuzumab (GA-101) and ofatumumab have been recently approved for the treatment of comorbid patients. Bendamustine is available for first-line treatment of patients ineligible for fludarabine, cyclophosphamide, and rituximab (FCR). High-dose glucocorticoids combined with rituximab represent a promising option for refractory CLL; ofatumumab is approved for fludarabine- and alemtuzumab-refractory patients. Allogeneic stem cell transplantation is the only curative option but is feasible in a highly selected group of patients only. The novel small molecule inhibitors ibrutinib and idelalisib have been recently approved for relapsed/refractory CLL. This review provides practical advice for diagnosis, prognostication and treatment of CLL. PMID- 27186196 TI - Effects of stress management program on the quality of nursing care and intensive care unit nurses. AB - BACKGROUND: High level of stress in intensive care unit nurses affects the quality of their nursing care. Therefore, this study aimed to determine the effects of a stress management program on the quality of nursing care of intensive care unit nurses. MATERIALS AND METHODS: This study is a randomized clinical trial that was conducted on 65 nurses. The samples were selected by stratified sampling of the nurses working in intensive care units 1, 2, 3 in Al Zahra Hospital in Isfahan, Iran and were randomly assigned to two groups. The intervention group underwent an intervention, including 10 sessions of stress management that was held twice a week. In the control group, placebo sessions were held simultaneously. Data were gathered by demographic checklist and Quality Patient Care Scale before, immediately after, and 1 month after the intervention in both groups. Then, the data were analyzed by Student's t-test, Mann-Whitney, Chi-square, Fisher's exact test, and analysis of variance (ANOVA) through SPSS software version 18. RESULTS: Mean scores of overall and dimensions of quality of care in the intervention group were significantly higher immediately after and 1 month after the intervention, compared to pre-intervention (P < 0.001). The results showed that the quality of care in the intervention group was significantly higher immediately after and 1 month after the intervention, compared to the control group (P < 0.001). CONCLUSIONS: As stress management is an effective method to improve the quality of care, the staffs are recommended to consider it in improvement of the quality of nursing care. PMID- 27186195 TI - Strangulation and necrosis of right hemicolon as an extremely rare complication of Spigelian hernia. PMID- 27186197 TI - The effects of two methods of reflexology and stretching exercises on the severity of restless leg syndrome among hemodialysis patients. AB - BACKGROUND: Restless leg syndrome prevalence is high among the patients undergoing hemodialysis. Due to several side effects of medicational treatments, the patients prefer non-medicational methods. Therefore, the present study aimed to investigate the effects of two methods of reflexology and stretching exercises on the severity of restless leg syndrome among patients undergoing hemodialysis. MATERIALS AND METHODS: This study is a randomized clinical trial that was done on 90 qualified patients undergoing hemodialysis in selected hospitals of Isfahan, who were diagnosed with restless leg syndrome through standard restless leg syndrome questionnaire. They were randomly assigned by random number table to three groups: Reflexology, stretching exercises, and control groups through random allocation. Foot reflexology and stretching exercises were conducted three times a week for 30-40 min within straight 4 weeks. Data analysis was performed by SPSS version 18 using descriptive and inferential statistical analyses [one way analysis of variance (ANOVA), paired t-test, and least significant difference (LSD) post hoc test]. RESULTS: There was a significant difference in the mean scores of restless leg syndrome severity between reflexology and stretching exercises groups, compared to control (P < 0.001), but there was no significant difference between the two study groups (P < 0.001). Changes in the mean score of restless leg syndrome severity were significantly higher in reflexology and stretching exercises groups compared to the control group (P < 0.001), but it showed no significant difference between reflexology massage and stretching exercises groups. CONCLUSIONS: Our obtained results showed that reflexology and stretching exercises can reduce the severity of restless leg syndrome. These two methods of treatment are recommended to the patients. PMID- 27186198 TI - The relationship between personality traits and sexual self-esteem and its components. AB - BACKGROUND: Women's sexual self-esteem is one of the most important factors that affect women's sexual satisfaction and their sexual anxiety. Various aspects of sexual life are blended with the entire personality. Determining the relationship between personality traits and self-concept aspects such as sexual self-esteem leads to better understanding of sexual behavior in people with different personality traits and helps in identifying the psychological variables affecting their sexual performance. The aim this study was to determine the relationship between personality traits and sexual self-esteem. MATERIALS AND METHODS: This correlation study was performed on 127 married women who referred to selected health care centers of Mashhad in 2014-2015. Data collection tools included NEO personality inventory dimensions and Zeanah and Schwarz sexual self-esteem questionnaire. Data were analyzed through Pearson correlation coefficient test and stepwise regression model. RESULTS: The results of Pearson correlation test showed a significant relationship between neuroticism personality dimension (r = 0.414), extroversion (r = 0.363), agreeableness (r = 0.420), and conscientiousness (r = 0.364) with sexual self-esteem (P < 0.05). The relationship between openness with sexual self-esteem was not significant (P > 0.05). In addition, based on the results of the stepwise regression model, three dimensions of agreeableness, neuroticism, and extraversion could predict 27% of the women's sexual self-esteem variance. CONCLUSIONS: The results showed a correlation between women's personality characteristics and their sexual self esteem. Paying attention to personality characteristics may be important to identify at-risk group or the women having low sexual self-esteem in premarital and family counseling. PMID- 27186199 TI - Physical violence against health care workers: A nationwide study from Iran. AB - BACKGROUND: Workplace violence is a serious and problematic phenomenon in health care settings. Research shows that health care workers are at the highest risk of such violence. The aim of this study was to address the frequency of physical violence against Iranian health personnel, their response to such violence, as well as the contributing factors to physical violence. MATERIALS AND METHODS: A cross-sectional study was conducted in 2011, in which 6500 out of 57,000 health personnel working in some teaching hospitals were selected using multi-stage random sampling. Data were collected using the questionnaire of "Workplace Violence in the Health Sector" developed by the International Labor Organization, the International Council of Nurses, the World Health Organization, and the Public Services International. RESULTS: The findings revealed that 23.5% of the participants were exposed to physical violence in the 12 months prior to the study. Nurses were the main victims of physical violence (78%) and patients' families were the main perpetrators of violence (56%). The most common reaction of victims to physical violence was asking the aggressor to stop violence (45%). Lack of people's knowledge of employees' tasks was the most common contributing factor to physical violence (49.2%). CONCLUSIONS: Based on the results, legislating appropriate laws in order to prevent and control violence in the workplace is necessary. Moreover, developing educational programs to manage the incidence of physical violence should be on health centers' agenda. PMID- 27186200 TI - The perception of primiparous mothers of comfortable resources in labor pain (a qualitative study). AB - BACKGROUND: Natural delivery is the most painful event that women experience in their lifetime. That is why labor pain relief has long been as one of the most important issues in the field of midwifery. Thus, the present study aims to explore the perception of primiparous mothers on comfortable resources for labor pain. MATERIALS AND METHODS: In the present study, qualitative content analysis technique was used. The participants had singleton pregnancy with normal vaginal delivery. These women referred to the Imam Javad Health Center within 3-5 days after delivery for screening thyroid of their babies. RESULTS: During the content analysis process, five themes emerged that indicated the nature and dimensions of the primiparous mothers' perception of comfortable resources. These themes were: "religious and spiritual beliefs," "use of analgesic methods" (medicinal and non medicinal), "support and the continuous attendance of midwife and delivery room personnel," "family's and husband's support during pregnancy and in vaginal delivery encouragement," and finally "lack of familiarity with the delivery room and lack of awareness about structured delivery process." CONCLUSIONS: The results showed that mothers received more comfort from human resources than from the environment and modern equipment. Despite the need for specialized midwife with modern technical facilities, this issue shows the importance of highlighting the role of midwife and humanistic midwife care. Therefore, considering midwives and the standardization of human resources in health centers are more important than physical standardization. This will result in midwife interventions being performed with real understanding of the patients' needs. PMID- 27186201 TI - The effect of inhalation aromatherapy with damask rose (Rosa damascena) essence on the pain intensity after dressing in patients with burns: A clinical randomized trial. AB - BACKGROUND: Pain is one of the common problems encountered by patients with burns, which increases after each dressing. This study aimed to investigate the effect of inhalation aromatherapy with damask rose essence on the pain of patients with burns that is caused after dressing. MATERIALS AND METHODS: A randomized clinical trial was conducted on 50 patients with second- and third degree burn wounds. The baseline pain of the patients was assessed 30 min before they entered into the dressing room on the first and second days of intervention. The patients in the experimental group inhaled five drops of damask rose essence 40% in distilled water, while those in the control group inhaled five drops of distilled water as placebo. The pain intensity was assessed using Visual Analogue Scale at 15 and 30 min after the patients exited from the dressing room. Data were analyzed by SPSS (version 18) using descriptive and inferential statistics. RESULTS: There was significant difference between the mean of pain intensity before and after intervention at 15 and 30 min after dressing (P < 0.001). Moreover, there was significant difference in reduction of pain intensity before and after aromatherapy in the experimental group (P < 0.05). Also, there was a significant reduction in severity of pain after dressing in the experimental group compared with the control group (P < 0.05). CONCLUSIONS: Inhalation aromatherapy with damask rose could be effective for relieving the pain caused after dressing in patients with burns. Therefore, it could be suggested as a complementary therapy in burn patients for pain relief. PMID- 27186202 TI - Investigating the effect of therapeutic touch on the intensity of acute chemotherapy-induced vomiting in breast cancer women under chemotherapy. AB - BACKGROUND: Nausea and vomiting are the worst and the most prevalent complications experienced by 70-80% of patients. Complementary treatments including therapeutic touch are cost-effective and low-risk, independent nursing interventions. Present research aims at investigating the effect of therapeutic touch on the intensity of acute chemotherapy-induced vomiting in these patients. MATERIALS AND METHODS: As a single-blind, randomized clinical trial, the present research was carried out on women with breast cancer undergoing chemotherapy in Isfahan, Iran. The subjects were divided into three groups of control, placebo, and intervention. The intervention was applied to each patient once for 20 min on the aura (human energy field) focusing on solar chakra. Data gathering instruments included demographic questionnaire and acute vomiting intensity scale. RESULTS: There was a significant difference among the three groups (and also after the intervention) (P < 0.0001). Paired comparisons among the groups using Mann-Whitney test showed that there was a statistically significant difference between the control group and the intervention group and between the control group and the placebo group (P < 0.0001). However, there was no significant difference between the placebo and intervention groups (P = 0.07). CONCLUSIONS: Therapeutic touch was effective in reducing vomiting in the intervention group. However, the patients experienced lower-intensity vomiting which may be because of presence of a therapist and probably the reduced anxiety related to an additional intervention. So, further research is recommended considering the placebo group and employing another person in addition to the therapist, who is not skilled for this technique. PMID- 27186203 TI - Contextual factors affecting autonomy for patients in Iranian hospitals: A qualitative study. AB - BACKGROUND: Consideration of patient autonomy is an essential element in individualized, patient-centered, ethical care. Internal and external factors associated with patient autonomy are related to culture and it is not clear what they are in Iran. The aim of this study was to explore contextual factors affecting the autonomy of patients in Iranian hospitals. MATERIALS AND METHODS: This was a qualitative study using conventional content analysis methods. Thirty four participants (23 patients, 9 nurses, and 2 doctors) from three Iranian teaching hospitals, selected using purposive sampling, participated in semi structured interviews. Unstructured observation and filed notes were other methods for data collection. The data were subjected to qualitative content analysis and analyzed using the MAXQDA-10 software. RESULTS: Five categories and sixteen subcategories were identified. The five main categories related to patient autonomy were: Intrapersonal factors, physical health status, supportive family and friends, communication style, and organizational constraints. CONCLUSIONS: In summary, this study uncovered contextual factors that the care team, managers, and planners in the health field should target in order to improve patient autonomy in Iranian hospitals. PMID- 27186204 TI - The association between abdominal obesity and characteristics of migraine attacks in Iranian adults. AB - BACKGROUND: Migraine is a primary headache disorder that affects the neurovascular system. Recent studies have shown that migraine patients with general obesity have higher characteristics of migraine attacks compared with normal weight patients, but data on central obesity are scarce. This study was done to assess the relationship between central obesity and the characteristics of migraine attacks in migraine patients. MATERIALS AND METHODS: This cross sectional study was conducted on 129 migraine patients (28 men and 101 women), aged 15-67 years, in Isfahan, Iran. Anthropometric measurements such as waist circumference (WC), hip circumference (HC), waist-hip ratio (WHR) and waist height ratio (WHtR), as well as characteristics of migraine attacks such as severity, frequency, duration, and headache diary result (HDR) was determined for each participant. Linear regression was used to examine the association between anthropometric measurements and characteristics of migraine attacks. P value less than 0.05 was considered significant. RESULTS: WC, WHR, and WHtR were positively associated with the severity (P-value: WC: 0.002, WHR: 0.002, WHtR: 0.001) and frequency (P-value: WC: 0.006, WHR: 0.01, WHtR: 0.002) of migraine attacks. Moreover, we found a significant association between WC (P = 0.001), WHR (P = 0.004), and WHtR (P < 0.001) with HDR. No significant relationship was observed between central obesity indicators and duration of migraine attacks. CONCLUSIONS: Central obesity indicators were positively associated with the severity and frequency of migraine attacks as well as HDR, but not with duration of attacks. Based on our findings, it can be concluded that weight loss may decrease the characteristics of migraine attacks. PMID- 27186205 TI - Bitter experiences of elderly parents of children with intellectual disabilities: A phenomenological study. AB - BACKGROUND: It is predicted that over the next 30 years, there will be a significant increase in the number of elderly parents who care for their children with intellectual disability. This paper is part of a larger qualitative study which investigated the unpleasant experiences of these parents. MATERIALS AND METHODS: A phenomenological approach was adopted and data were collected through unstructured in-depth interviews with elderly parents of children with intellectual disability. The data were analyzed using Colaizzi's seven-step method. RESULTS: "Bitterness" is one of the four emergent themes extracted in this study which has five theme clusters: inappropriate behavior toward the child in the society, the society's failure to support the child with intellectual disability, sorrows experienced by parents, the child's problems, and barriers in the care of the child with intellectual disability. One significant barrier in the last theme cluster is limitations due to aging. CONCLUSIONS: The findings of this study suggest that the elderly parents of children with intellectual disability experience many sorrows and unpleasant feelings, but they mostly consider the social factors as the cause of problems and not the presence of the child. The results also indicate that older parents cannot look after the child as before in their old age; so, future well-designed studies are required for identification of the process of supporting them. PMID- 27186206 TI - Validity and reliability of the persian version of templer death anxiety scale in family caregivers of cancer patients. AB - BACKGROUND: Due to increasing recognition of the importance of death anxiety for understanding human nature, it is important that researchers who investigate death anxiety have reliable and valid methodology to measure. The purpose of this study was to evaluate the validity and reliability of the Persian version of Templer Death Anxiety Scale (TDAS) in family caregivers of cancer patients. MATERIALS AND METHODS: A sample of 326 caregivers of cancer patients completed a 15-item questionnaire. Principal components analysis (PCA) followed by a varimax rotation was used to assess factor structure of the DAS. The construct validity of the scale was assessed using exploratory and confirmatory factor analyses. Convergent and discriminant validity were also examined. Reliability was assessed with Cronbach's alpha coefficients and construction reliability. RESULTS: Based on the results of the PCA and consideration of the meaning of our items, a three factor solution, explaining 60.38% of the variance, was identified. A confirmatory factor analysis (CFA) then supported the adequacy of the three domain structure of the DAS. Goodness-of-fit indices showed an acceptable fit overall with the full model {chi(2)(df) = 262.32 (61), chi(2)/df = 2.04 [adjusted goodness of fit index (AGFI) = 0.922, parsimonious comparative fit index (PCFI) = 0.703, normed fit Index (NFI) = 0.912, CMIN/DF = 2.048, root mean square error of approximation (RMSEA) = 0.055]}. Convergent and discriminant validity were shown with construct fulfilled. The Cronbach's alpha and construct reliability were greater than 0.70. CONCLUSIONS: The findings show that the Persian version of the TDAS has a three-factor structure and acceptable validity and reliability. PMID- 27186207 TI - An investigation on the quality of midwifery services from the viewpoint of the clients in Isfahan through SERVQUAL model. AB - BACKGROUND: Quality of care is of great importance in health services as these services have the important mission to preserve health, and to give care to the society. The present study aimed to investigate the quality of midwifery services from the viewpoint of the clients, under coverage of health care centers in Isfahan, through SERVQUAL model. MATERIALS AND METHODS: This descriptive and analytical study was conducted on 218 subjects in 2014. Study population comprised the women referring to midwifery services clinics in health care centers in Isfahan. Data of the subjects (n = 218) were collected by SERVQUAL model containing the dimensions of tangibles, reliability, responsiveness, assurance, and empathy. Data were analyzed by paired t-test, Spearman and Pearson correlation coefficients, and independent t-test through SPSS 20. RESULTS: There was a negative gap in all five relevant dimensions of giving services. The widest gap was in the mean of dimension of tangibles (-1.5), and the narrowest gap was in the dimension of assurance (-0.9). There was no significant association between the scores of expectations and perceptions, and age, education level, occupation, and marital status. CONCLUSIONS: The obtained negative gap showed that the level of service receivers' perception from existing condition was far from their expectation, and there was a wide gap between attaining their satisfaction with midwifery services and their expectation and reaching their appropriate level of services. PMID- 27186208 TI - Iran's health policymakers' views on barriers and facilitators of nurse prescribing in their context: A qualitative study. AB - BACKGROUND: In most countries, one of the main reasons for developing more advanced roles for nurses is to improve access to care in the context of limited number of doctors. It is considered that the introduction of major policy initiatives, such as nurse prescribing, requires high-level discussion and policy development to ensure successful implementation. This study aimed to identify the barriers and facilitators of nurse prescribing based on policymakers' views in Iran. MATERIALS AND METHODS: This qualitative study was based on conventional content analysis approach. A purposeful sample of 14 participants were recruited, including 6 members of the Nursing Board, 6 members of the Iranian Nursing Organization, and 2 senior employees of Iran's Ministry of Health and Medical Education. Data were gathered through in-depth semi-structured interviews. Interviews were audio-recorded and transcribed verbatim. RESULTS: The four emerged categories as facilitators of nurse prescribing were labeled "positive views of health policymakers," "human resources capabilities," "non-medical prescribing experiences," and "governmental and non-governmental organizational activities." The four extracted categories as barriers of nurse prescribing were "socio-cultural factors," "organizational factors," "educational barriers," and "human barriers." CONCLUSIONS: Barriers and facilitating factors should be considered in order to bring about organizational policy changes and improve perspectives. Nurse prescribing requires the efforts of involved managers and authorities for development and modernization. The results of this study can serve as a compressed resource for policymakers and managers to identify the effective issues on nurse prescribing and can help them to plan for the implementation of nurse prescribing. PMID- 27186209 TI - Effect of head nurse empowerment program on staff nurses' job satisfaction at two educational hospitals in Rasht, Iran. AB - BACKGROUND: Job satisfaction of nurses is an important concept in nursing profession because it influences nursing care. Head nurses play a crucial role in the job satisfaction of nurse staffs. The current study, therefore, aimed to investigate the effect of Head Nurse Empowerment Program (HNEP) on job satisfaction of nurses. MATERIALS AND METHODS: This quasi-experimental study was conducted at two educational hospitals in Rasht, Iran. Of 160 staff nurses who were working in eight medical-surgical wards and two Intensive Care Units, 60 were recruited using simple random sampling method. The samples were randomly assigned to control and experimental groups. The HNEP was applied to promote the management skills among nurses, which included technical, communicational, perceptional, and diagnostic skills. The data were collected using nurses' job satisfaction questionnaire and analyzed using the Mann-Whitney and Wilcoxon Singed Ranks tests. P < 0.05 was set as the significance level. RESULTS: There was a significant difference in the job satisfaction of nurse staff within the experimental group on comparing pre- and post-HNEP phases [78 (65.50) vs. 78 (65.50); P < 0.001]. The job satisfaction also differed between the control and experimental groups [60 (82.25) vs. 128.5 (51.75); P < 0.001]. However, no significant difference [62 (78.75) vs. 60 (82.25); P = 0.129] was found within the control group. The number of satisfied nurse staffs increased in the experimental group from approximately 25% to 76% after HNEP. CONCLUSIONS: The HNEP can be used as a promoting tool in the nursing profession. Increasing head nurses' management skills can result in job satisfaction among the staff nurses. PMID- 27186211 TI - Effect of peer education on the noise management in Iranian neonatal intensive care unit. AB - BACKGROUND: Advancements in neonatal intensive care unit (NICU) science and technology have increased the survival rate of preterm infants. Despite these advances, they are still facing with neurobehavioral problems. Noise level in NICU is a potential source of stress for preterm infants. It should be decreased to the standard level as much as possible. The purpose of this study was to evaluate the effect of peer education on the performance of staff in noise management in the NICU. MATERIALS AND METHODS: A pre-post test quasi-experimental design was used. Fifty-eight staff members (nurses and physicians) participated in this study. Sound pressure levels were measured before and after the intervention. Peer education program formed the intervention. The staff performance in noise management was evaluated before and after the intervention by using a questionnaire. Data analysis was done by using t-test. RESULTS: The results of the study showed that the mean sound level in different environments significantly decreased after the intervention. It reached from 86.7 to 74.9 dB in the center of unit and from 68.2 to 48.50 dB in the infants' bedside (P < 0.0001). The mean score of the staff performance in noise management significantly increased after the intervention, compared to the pre-intervention score. It increased from 74.6 to 83.4 (P < 0.0001). CONCLUSIONS: Peer education was found to be successful in noise management because behavioral changes were done to avoid generating unnecessary noise by the staff. PMID- 27186210 TI - Effective strategies for reducing maternal mortality in Isfahan University of Medical Sciences, 2014. AB - BACKGROUND: Maternal mortality rate is among the most important health indicators. This indicator is a function of factors that are related to pregnant women; these factors include economic status, social and family life of the pregnant woman, human resources, structure of the hospitals and health centers, and management factors. Strategic planning, with a comprehensive analysis and coverage of all causes of maternal mortality, can be helpful in improving this indicator. MATERIALS AND METHODS: This research is a descriptive exploratory study. After needs assessment and review of the current situation through eight expert panel meetings and evaluating the organization's internal and external environment, the strengths, weaknesses, threats, and opportunities of maternal mortality reduction were determined. Then, through mutual comparison of strengths/opportunities, strengths/threats, weaknesses/opportunities, and weaknesses/threats, WT, WO, ST, and SO strategies and suggested activities of the researchers for reducing maternal mortality were developed and dedicated to the areas of education, research, treatment, and health, as well as food and drug administration to be implemented. RESULTS: In the expert panel meetings, seven opportunity and strength strategies, eight strength and threat strategies, five weakness and threat strategies, and seven weakness and opportunity strategies were determined and a strategic plan was developed. CONCLUSIONS: Dedication of the developed strategies to the areas of education, research, treatment, and health, as well as food and drug administration has coordinated these areas to develop Ministry of Health indicators. In particular, it emphasizes the key role of university management in improving the processes related to maternal health. PMID- 27186212 TI - The effect of nitric oxide releasing cream on healing pressure ulcers. AB - BACKGROUND: Pressure ulcer is one of the main concerns of nurses in medical centers around the world, which, if untreated, causes irreparable problems for patients. In recent years, nitric oxide (NO) has been proposed as an effective method for wound healing. This study was conducted to determine the effect of nitric oxide on pressure ulcer healing. MATERIALS AND METHODS: In this clinical trial, 58 patients with pressure ulcer at hospitals affiliated to Ahvaz Jundishapur University of Medical Sciences were homogenized and later divided randomly into two groups of treatment (nitric oxide cream; n = 29) and control (placebo cream; n = 29). In this research, the data collection tool was the Pressure Ulcer Scale for Healing (PUSH). At the outset of the study (before using the cream), the patients' ulcers were examined weekly in terms of size, amount of exudates, and tissue type using the PUSH tool for 3 weeks. By integrating these three factors, wound healing was determined. Data were analyzed using SPSS. RESULTS: Although no significant difference was found in terms of the mean of score size, the amount of exudates, and the tissue type between the two groups, the mean of total score (healing) between the two groups was statistically significant (P = 0.04). CONCLUSIONS: Nitric oxide cream seems to accelerate wound healing. Therefore, considering its easy availability and cost-effectiveness, it can be used for treating pressure ulcers in the future. PMID- 27186213 TI - The effects of progressive muscular relaxation and breathing control technique on blood pressure during pregnancy. AB - BACKGROUND: Hypertensive disorders in pregnancy are the main cause of maternal and fetal mortality; however, they have no definite effective treatment. The researchers aimed to study the effects of progressive muscular relaxation and breathing control technique on blood pressure (BP) during pregnancy. MATERIALS AND METHODS: This three-group clinical trial was conducted in Mashhad health centers and governmental hospitals. Sixty pregnant (after 20 weeks of gestational age) women with systolic BP >= 135 mmHg or diastolic BP >= 85 mmHg were assigned to three groups. Progressive muscular relaxation and breathing control exercises were administered to the two experimental groups once a week in person and in the rest of the days by instructions given on a CD for 4 weeks. BP was checked before and after the interventions. BP was measured before and after 15 min subjects' waiting without any especial intervention in the control group. RESULTS: After 4 weeks of intervention, the systolic (by a mean of 131.3 to 117.2, P = 0.001 and by a mean of 131.05 to 120.5, P = 0.004, respectively) and diastolic (by a mean of 79.2 to 72.3, P = 0.001 and by a mean of 80.1 to 76.5, P = 0.047, respectively) BPs were significantly decreased in progressive muscular relaxation and breathing control groups, but they were not statistically significant in the control group. CONCLUSIONS: The interventions were effective on decreasing systolic and diastolic BP to normal range after 4 weeks in both the groups. The effects of both the interventions were more obvious on systolic BP compared to diastolic BP. PMID- 27186215 TI - Expiratory rib cage compression, endotracheal suctioning, and vital signs. PMID- 27186214 TI - Effects of thoracic squeezing on airway secretion removal in mechanically ventilated patients. AB - BACKGROUND: Accumulation of secretions in the airways of patients with an endotracheal tube and mechanical ventilation will have serious consequences. One of the most common methods of airway clearance is endotracheal suctioning. In order to facilitate discharge of airway secretion resulting in promotion of gas exchange, chest physiotherapy techniques can be used at the time of expiration before suction. MATERIALS AND METHODS: In this clinical trial with a cross-over design, 50 mechanically ventilated patients admitted to intensive care units (ICUs) were randomly divided into two groups of thoracic squeezing. In each patient, two interventions of endotracheal suctioning were conducted, one with and the other without thoracic squeezing during exhalation, with a 3 h gap between the two interventions and an elapse of three respiratory cycles between the number of compressions. Sputum secreted was collected in a container connected to a suction catheter and weighed. Data were recorded in data gathering forms and analyzed using descriptive and inferential statistics (Wilcoxon and independent t-test, Chi-square) in SPSS version 16. RESULTS: Findings showed that the mean weight of the suction secretions removed from airway without thoracic squeezing was 1.35 g and that of suction secretions removed by thoracic squeezing was 1.94 g. Wilcoxon test showed a significant difference regarding the rate of secretion between the two techniques (P = 0.003). CONCLUSIONS: According to the study findings, endotracheal suction with thoracic squeezing on expiration helps airway secretion discharge more than suction alone in patients on mechanical ventilators and can be used as an effective method. PMID- 27186216 TI - Diffuse alveolar hemorrhage and recombinant factor VIIa treatment in pediatric patients. AB - Diffuse alveolar hemorrhage (DAH) is a life-threatening pulmonary complication in patients with hematologic malignancies or autoimmune disorders. The current treatment options, which include corticosteroids, transfusions, extracorporeal membrane oxygenation (ECMO), and immunosuppressants, have been limited and largely unsuccessful. Recombinant activated factor VII (rFVIIa) has been successfully administered, either systemically or bronchoscopically, to adults for the treatment of DAH, but there are few data on its use in pediatric patients. The current literature in the PubMed database was reviewed to evaluate the efficacy and risk of rFVIIa treatment for DAH in pediatric patients. This review discusses the diagnosis and treatment of DAH, as well as a new treatment paradigm that includes rFVIIa. Additionally, the risks and benefits of off-label use of rFVIIa in pediatric patients are discussed. PMID- 27186217 TI - Reference values of lead in blood and related factors among Korean adolescents: the Korean National Health and Nutrition Examination Survey 2010-2013. AB - PURPOSE: This study aimed to assess the reference values and factors influencing blood lead levels among Korean adolescents. METHODS: The study population consisted of 1,585 adolescents (801 males, 784 females; aged 10-19 years) who participated in the Korea National Health and Nutrition Examination Survey 2010 2013. We analyzed blood lead concentrations in relation to demographic/lifestyle characteristics for all participants. "Reference values" of blood lead levels were calculated as the upper limit of the 95% confidence interval of the 95th percentile. RESULTS: The average "reference value" for blood lead concentrations among Korean adolescents was 2.25 ug/dL (2.49 ug/dL for males, 2.07 ug/dL for females), and the geometric mean of the blood lead concentrations was 1.34 ug/dL. Males had higher blood lead concentrations than females (male, 1.48 ug/dL; female, 1.19 ug/dL; P<0.001). Elementary school students had higher blood lead concentrations than junior and senior high school students (1.44 ug/dL vs. 1.31 ug/dL, P<0.001). Participants living in detached houses had higher blood lead concentrations than those living in apartments (P<0.001) and current smokers had higher concentrations than nonsmokers or participants with secondhand smoke exposure (P<0.05). Additionally, participants with excessive alcohol consumption had higher levels than non-drinkers (P<0.001). CONCLUSION: This study provides national reference data on blood lead concentrations stratified by demographic and lifestyle factors among Korean adolescents. Further studies are needed to elucidate the relationship between increased lead exposure and demographic factors including type of housing. PMID- 27186219 TI - Diagnostic value of the Vesikari Scoring System for predicting the viral or bacterial pathogens in pediatric gastroenteritis. AB - PURPOSE: To evaluate the diagnostic value of the Vesikari Scoring System (VSS) as an early predictor of pathogens in children with acute gastroenteritis (AG). METHODS: In this retrospective study, the VSS score, absolute neutrophil count (ANC), and C-reactive protein (CRP) levels were analyzed in 107 hospitalized children with AG, aged 6 months to 17 years. Patients were divided into nonspecific, viral, and bacterial groups according to the pathogens detected using a multiplex polymerase chain reaction (PCR) test. RESULTS: Patients in the bacterial group had significantly higher CRP values and VSS scores compared to those in the viral group and significantly higher VSS scores compared to those in the nonspecific group (P<0.05). Patients in the viral group had significantly higher VSS scores than those in the nonspecific group (P<0.05). Logistic regression analysis revealed that VSS was the most effective diagnostic tool for predicting the type of pathogen (P<0.05). The area under the receiver operating characteristics curve of VSS was significantly greater than that for ANC and CRP (P<0.05). At a cutoff point of 10 in the VSS, an acceptable diagnostic accuracy could be achieved for distinguishing between bacterial and viral pathogens in AG. CONCLUSION: VSS can be considered a useful and reliable infectious marker for pediatric gastroenteritis. VSS may be a good early predictor of the type of pathogen, enabling development of a treatment plan before results from a stool culture or PCR test are available. PMID- 27186218 TI - Recent viral pathogen in acute gastroenteritis: a retrospective study at a tertiary hospital for 1 year. AB - PURPOSE: Viral gastroenteritis among children is mainly caused by rotavirus, norovirus, astrovirus, or adenovirus strains. However, changing socioeconomic conditions and a rotavirus vaccination program may be affecting the prevalence of these viral infections. Therefore, we aimed to elucidate the season-specific trends in viral infections for facilitating prophylaxis and surveillance in our region. METHODS: We evaluated 345 pediatric patients (203 males, 142 females; age, 1 month to 16 years) who visited the CHA Bundang Medical Center because of gastroenteric symptoms between June 2014 and May 2015. The specimens were simultaneously tested for norovirus, rotavirus, astrovirus, and adenovirus via multiplex reverse transcription polymerase chain reaction. Clinical characteristics of patients were analyzed retrospectively. RESULTS: The most common virus was norovirus, followed by rotavirus, adenovirus, and astrovirus. Of all viral infections, 45.2% occurred mainly between 6 and 24 months of age; in particular, norovirus infection mostly occurred in all age groups except those below 6 months of age, when rotavirus was most prevalent. In addition, seasonal variation was observed, such as norovirus infection from December to February, rotavirus infection from February to April, and adenovirus infection from July to October. CONCLUSION: Our results showed that the most common cause of acute pediatric viral gastroenteritis had changed from rotavirus to norovirus in our patients, because of effective rotaviral vaccination. We recommend the management of food and personal hygiene in accordance with age or seasons as well as active vaccination for preventing viral gastroenteritis. PMID- 27186220 TI - A nationwide study of children and adolescents with pneumonia who visited Emergency Department in South Korea in 2012. AB - PURPOSE: Acute respiratory infection, particularly pneumonia, is the most common cause of hospitalization and death among children in developing nations. This study aimed to investigate the characteristics of children and adolescents with pneumonia who visited Emergency Department (ED) in South Korea in 2012. METHODS: We analyzed National Emergency Department Information System (NEDIS) records from 146 EDs in South Korea for all pediatric patients aged <=18 years who were diagnosed with pneumonia between January and December 2012. RESULTS: Among 38,415 subjects, the male-to-female ratio was 1:0.8. Patients aged <12 months comprised 18.0% of the study population; those aged 1 to 3 years, 54.4%; those aged 4 to 6 years, 16.8%; those aged 7 to 12 years, 7.4%; and those aged 13 to 18 years, 3.4%. Presentation rates were highest in April, followed by January, March, and May. The hospital admission rate was 43.5%, of which 2.6% were in intensive care units. The mortality rate was 0.02%. Based on the International Classification of Diseases, 10th Revision, diagnostic codes, the types of pneumonia according to cause were viral pneumonia (29.0%), bacterial pneumonia (5.3%), Mycoplasmal pneumonia (4.5%), aspiration pneumonia (1.3%), and pneumonia of unknown origin (59.3%). CONCLUSION: Despite the limited data due to the ED data from the NEDIS lacking laboratory results and treatment information, this study reflects well the outbreak patterns among children and adolescents with pneumonia. Our results provide a basis for future studies regarding ED treatment for children and adolescents with pneumonia. PMID- 27186222 TI - Acute tubular necrosis as a part of vancomycin induced drug rash with eosinophilia and systemic symptoms syndrome with coincident postinfectious glomerulonephritis. AB - Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially fatal condition characterized by skin rash, fever, eosinophilia, and multiorgan involvement. Various drugs may be associated with this syndrome including carbamazepine, allopurinol, and sulfasalazine. Renal involvement in DRESS syndrome most commonly presents as acute kidney injury due to interstitial nephritis. An 11-year-old boy was referred to the Children's Hospital of Pusan National University because of persistent fever, rash, abdominal distension, generalized edema, lymphadenopathy, and eosinophilia. He previously received vancomycin and ceftriaxone for 10 days at another hospital. He developed acute kidney injury with nephrotic range proteinuria and hypocomplementemia. A subsequent renal biopsy indicated the presence of acute tubular necrosis (ATN) and late exudative phase of postinfectious glomerulonephritis (PIGN). Systemic symptoms and renal function improved with corticosteroid therapy after the discontinuation of vancomycin. Here, we describe a biopsy-proven case of severe ATN that manifested as a part of vancomycin-induced DRESS syndrome with coincident PIGN. It is important for clinicians to be aware of this syndrome due to its severity and potentially fatal nature. PMID- 27186221 TI - Usefulness of neutrophil-lymphocyte ratio in young children with febrile urinary tract infection. AB - PURPOSE: Acute pyelonephritis (APN) is a serious bacterial infection that can cause renal scarring in children. Early identification of APN is critical to improve treatment outcomes. The neutrophil-lymphocyte ratio (NLR) is a prognostic marker of many diseases, but it has not yet been established in urinary tract infection (UTI). The aim of this study was to determine whether NLR is a useful marker to predict APN or vesicoureteral reflux (VUR). METHODS: We retrospectively evaluated 298 pediatric patients (age<=36 months) with febrile UTI from January 2010 to December 2014. Conventional infection markers (white blood cell [WBC] count, erythrocyte sedimentation rate [ESR], C-reactive protein [CRP]), and NLR were measured. RESULTS: WBC, CRP, ESR, and NLR were higher in APN than in lower UTI (P<0.001). Multiple logistic regression analyses showed that NLR was a predictive factor for positive dimercaptosuccinic acid (DMSA) defects (P<0.001). The area under the receiver operating characteristic (ROC) curve was high for NLR (P<0.001) as well as CRP (P<0.001) for prediction of DMSA defects. NLR showed the highest area under the ROC curve for diagnosis of VUR (P<0.001). CONCLUSION: NLR can be used as a diagnostic marker of APN with DMSA defect, showing better results than those of conventional markers for VUR prediction. PMID- 27186224 TI - Blood glucose level after febrile convulsion. PMID- 27186223 TI - Complete occlusion of the right middle cerebral artery associated with Mycoplasma pneumoniae pneumonia. AB - We report a case of a 5-year-old girl who developed left hemiparesis and left facial palsy, 6 days after the initiation of fever and respiratory symptoms due to pneumonia. Chest radiography, conducted upon admission, showed pneumonic infiltration and pleural effusion in the left lung field. Brain magnetic resonance imaging showed acute ischemic infarction in the right middle cerebral artery territory. Brain magnetic resonance angiography and transfemoral cerebral angiography revealed complete occlusion of the right middle cerebral artery. Mycoplasma pneumoniae infection was identified by a 4-fold increase in IgG antibodies to M. pneumoniae between acute and convalescent sera by enzyme-linked immunosorbent assay. Fibrinogen and D-dimer levels were elevated, while laboratory exams in order to identify other predisposing factors of pediatric stroke were all negative. This is the first reported pediatric case in English literature of a M. pneumoniae-associated cerebral infarction involving complete occlusion of the right middle cerebral artery. PMID- 27186225 TI - Cognitive impairment in childhood onset epilepsy: up-to-date information about its causes. AB - Cognitive impairment associated with childhood-onset epilepsy is an important consequence in the developing brain owing to its negative effects on neurodevelopmental and social outcomes. While the cause of cognitive impairment in epilepsy appears to be multifactorial, epilepsy-related factors such as type of epilepsy and underlying etiology, age at onset, frequency of seizures, duration of epilepsy, and its treatment are considered important. In recent studies, antecedent cognitive impairment before the first recognized seizure and microstructural and functional alteration of the brain at onset of epilepsy suggest the presence of a common neurobiological mechanism between epilepsy and cognitive comorbidity. However, the overall impact of cognitive comorbidity in children with epilepsy and the independent contribution of each of these factors to cognitive impairment have not been clearly delineated. This review article focuses on the significant contributors to cognitive impairment in children with epilepsy. PMID- 27186226 TI - Modification of nutrition strategy for improvement of postnatal growth in very low birth weight infants. AB - PURPOSE: To identify the effects of modified parenteral nutrition (PN) and enteral nutrition (EN) regimens on the growth of very low birth weight (VLBW) infants. METHODS: The study included VLBW infants weighing <1,500 g, admitted to Chungnam National University Hospital between October 2010 and April 2014, who were alive at the time of discharge. Subjects were divided according to 3 periods: period 1 (n=37); prior to the PN and EN regimen being modified, period 2 (n=50); following the PN-only regimen modification, period 3 (n=37); following both PN and EN regimen modification. The modified PN regimen provided 3 g/kg/day of protein and 1 g/kg/day of lipid on the first day of life. The modified EN regimen provided 3.5-4.5 g/kg/day of protein and 150 kcal/kg/day of energy. We investigated growth rate, anthropometric measurements at 40 weeks postconceptional age (PCA) and the incidence of extrauterine growth restriction (EUGR) at 40 weeks PCA. RESULTS: Across the 3 periods, clinical characteristics, including gestational age, anthropometric measurements at birth, multiple births, sex, Apgar score, surfactant use and PDA treatment, were similar. Growth rates for weight and height, from time of full enteral feeding to 40 weeks PCA, were higher in period 3. Anthropometric measurements at 40 weeks PCA were greatest in period 3. Incidence of weight, height and head circumference EUGR at 40 weeks PCA decreased in period 3. CONCLUSION: Beginning PN earlier, with a greater supply of protein and energy during PN and EN, is advantageous for postnatal growth in VLBW infants. PMID- 27186228 TI - Prediction of nonresponsiveness to medium-dose intravenous immunoglobulin (1 g/kg) treatment: an effective and safe schedule of acute treatment for Kawasaki disease. AB - PURPOSE: Medium-dose (1 g/kg) intravenous immunoglobulin (IVIG) is effective in the majority of patients with Kawasaki disease (KD) but some patients who do not respond to medium-dose IVIG are at high risk for the development of coronary artery lesions (CALs). The purpose of this study was to identify the clinical predictors associated with unresponsiveness to medium-dose IVIG and the development of CALs. METHODS: A retrospective study was performed in 91 children with KD who were treated with medium-dose IVIG at our institution from January 2004 to December 2013. We classified the patients into responders (group 1; n=68) and nonresponders (group 2; n=23). We compared demographic, laboratory, and echocardiographic data between the 2 groups. RESULTS: Multivariate logistic regression analysis identified 6 variables as predictors for resistance to medium dose IVIG. We generated a predictive scoring system assigning 1 point each for percentage of neutrophils >=65%, C-reactive protein>=100 mg/L, aspartate aminotransferase>=100 IU/L, and alanine aminotransferase>=100 IU/L, as well as 2 points for less than 5 days of illness, and serum sodium level<=136 mmol/L. Using a cutoff point of >=4 with this scoring system, we could predict nonresponsiveness to medium-dose IVIG with 74% sensitivity and 71% specificity. CONCLUSION: If a patient has a low-risk score in this system, medium-dose IVIG can be recommended as the initial treatment. Through this process, we can minimize the adverse effects of high-dose IVIG and incidence of CALs. PMID- 27186227 TI - Usefulness of anterior uveitis as an additional tool for diagnosing incomplete Kawasaki disease. AB - PURPOSE: There are no specific tests for diagnosing Kawasaki disease (KD). Additional diagnostic criteria are needed to prevent the delayed diagnosis of incomplete Kawasaki disease (IKD). This study compared the frequency of coronary artery lesions (CALs) in IKD patients with and without anterior uveitis (AU) and elucidated whether the finding of AU supported the diagnosis of IKD. METHODS: This study enrolled patients diagnosed with IKD at The Catholic University of Korea, Uijeongbu St. Mary's Hospital from January 2010 to December 2014. The patients were divided into 2 groups: group 1 included patients with IKD having AU; and group 2 included patients with IKD without AU. We analyzed the demographic and clinical data (age, gender, duration of fever, and the number of diagnostic criteria), laboratory results, and echocardiographic findings. RESULTS: Of 111 patients with IKD, 41 had uveitis (36.98%, group 1) and 70 did not (63.02%, group 2). Patients in group 1 had received a diagnosis and treatment earlier, and had fewer CALs (3 of 41, 1.7%) than those in group 2 (20 of 70, 28.5%) (P=0.008). All 3 patients with CALs in group 1 had coronary dilatation, while patients with CALs in group 2 had CALs ranging from coronary dilatation to giant aneurysm. CONCLUSION: The diagnosis of IKD is challenging but can be supported by the presence of features such as AU. Group 1 had a lower risk of coronary artery disease than group 2. Therefore, the presence of AU is helpful in the early diagnosis and treatment of IKD and can be used as an additional diagnostic tool. PMID- 27186229 TI - Correlation of B-type natriuretic peptide levels and echocardiographic parameters in preterm infants with patent ductus arteriosus. AB - PURPOSE: This study aimed to evaluate the correlation, according to postnatal age, between plasma B-type natriuretic peptide (BNP) levels and echocardiographic parameters for the assessment of patent ductus arteriosus (PDA) in preterm infants with respiratory distress. METHODS: We enrolled 42 preterm infants with respiratory distress who underwent serial echocardiographic evaluation with simultaneous plasma BNP measurements until ductal closure. The correlations between BNP levels and the following 4 representative echocardiographic parameters were studied: diameter of the ductus arteriosus (DA), ratio of the left atrial diameter to the aortic diameter (LA/Ao), ratio of the PDA diameter to the infant's left pulmonary artery diameter (PDA/LPA), and the antegrade diastolic flow of LPA (DFLPA). RESULTS: BNP levels were significantly correlated to the magnitude of the ductal shunt, comprising the DA diameter, PDA/LPA ratio, LA/Ao ratio, and antegrade DFLPA for the overall study period. The earliest significant correlation, starting from postnatal day 2, was observed between the LA/Ao ratio and BNP levels. The PDA/LPA ratio and the antegrade DFLPA showed significant correlations with BNP levels postnatal day 3 onward, and with the DA diameter, postnatal day 5 onward. CONCLUSION: BNP levels and echocardiographic parameters showed a positive correlation, but the significance of the correlations differed according to the postnatal age, especially during the first few days of life. PMID- 27186230 TI - Subclinical left ventricular dysfunction in children after hematopoietic stem cell transplantation for severe aplastic anemia: a case control study using speckle tracking echocardiography. AB - PURPOSE: Severe aplastic anemia (SAA), a fatal disease, requires multiple transfusion, immunosuppressive therapy, and finally, hematopoietic stem cell transplantation (HSCT) as the definitive treatment. We hypothesized that iron overloading associated with multiple transfusions and HSCTrelated complications may adversely affect cardiac function. Left ventricular (LV) function was assessed in children after HSCT for SAA. METHODS: Forty-six consecutive patients with a median age of 9.8 years (range, 1.5-18 years), who received HSCT for SAA and who underwent comprehensive echocardiography before and after HSCT, were included in this study. The data of LV functional parameters obtained using conventional echocardiography, tissue Doppler imaging (TDI), and speckle-tracking echocardiography (STE) were collected from pre- and post-HSCT echocardiography. These data were compared to those of 40 age-matched normal controls. RESULTS: In patients, the LV ejection fraction, shortening fraction, end-diastolic dimension, mitral early diastolic E velocity, TDI mitral septal E' velocity, and STE LV longitudinal systolic strain rate (SSR) decreased significantly after HSCT. Compared to normal controls, patients had significantly lower post-HSCT early diastolic E velocity and E/A ratio. On STE, patients had significantly decreased LV deformational parameters including LV longitudinal systolic strain (SS), SSR, and diastolic SR (DSR), and circumferential SS and DSR. Serum ferritin levels showed weak but significant correlations (P<0.05) with LV longitudinal SS and SSR and circumferential SS and DSR. CONCLUSION: Subclinical LV dysfunction is evident in patients after HSCT for SAA, and was associated with increased iron load. Serial monitoring of cardiac function is mandatory in this population. PMID- 27186231 TI - Concomitant use of corticosteroid and antimicrobials for liver abscesses in patients with chronic granulomatous disease. AB - Chronic granulomatous disease (CGD) is a rare inherited disorder caused by defective nicotinamide adenine dinucleotide phosphate oxidase enzyme and characterized by recurrent bacterial and fungal infections. Although liver abscess is a common manifestation of CGD, its management in CGD patients is not well-defined. In addition, the generalized guidelines for treating liver abscesses do not necessarily apply to CGD patients. Corticosteroids are commonly used to control granulomatous complications, such as inflammatory gastrointestinal and genitourinary lesions, in patients with CGD, Corticosteroids have also been used in combination with antimicrobials to treat refractory infections in patients with CGD. Because corticosteroids are capable of suppressing symptomatic inflammation, all potential infections must be adequately controlled prior to corticosteroid initiation. We report 3 typical CGD cases with liver abscesses refractory to conventional treatments that were successfully treated with the concomitant use of corticosteroid and antimicrobials. It remains unclear whether corticosteroid therapy is required for liver abscesses in CGD refractory to conventional treatments. However, based on our observations, use of corticosteroids in combination with optimal antimicrobials should be considered for refractory liver abscesses in CGD. PMID- 27186232 TI - Deficiency of antidiuretic hormone: a rare cause of massive polyuria after kidney transplantation. AB - A 15-year-old boy, who was diagnosed with Alport syndrome and end-stage renal disease, received a renal transplant from a living-related donor. On postoperative day 1, his daily urine output was 10,000 mL despite normal graft function. His laboratory findings including urine, serum osmolality, and antidiuretic hormone levels showed signs similar to central diabetes insipidus, so he was administered desmopressin acetate nasal spray. After administering the desmopressin, urine specific gravity and osmolality increased abruptly, and daily urine output declined to the normal range. The desmopressin acetate was tapered gradually and discontinued 3 months later. Graft function was good, and urine output was maintained within the normal range without desmopressin 20 months after the transplantation. We present a case of a massive polyuria due to transient deficiency of antidiuretic hormone with the necessity of desmopressin therapy immediately after kidney transplantation in a pediatric patient. PMID- 27186233 TI - The effect of interaction between Melanocortin-4 receptor polymorphism and dietary factors on the risk of metabolic syndrome. AB - BACKGROUND: Controversial data is available on the effect of the Melanocortin-4 receptor (MC4R) gene variation on metabolic syndrome (MetS) and ineffectiveness of diet in managing MetS. Effects of the interaction between MC4R polymorphism and dietary factors on MetS were investigated in this study. METHODS: Subjects of this nested case-control study were selected from among participants of Tehran Lipid and Glucose Study. Each case (n = 815) was pair matched randomly with a control by age (+/-5 years) and sex from among those who had not developed >=1 MetS components at the time that the corresponding case developed MetS. Dietary patterns were determined using factor analysis on 25 foods groups using a valid and reliable, 168-item semi-quantitative food frequency questionnaire (FFQ). MC4R rs12970134 were genotyped by Tetra-Primer ARMS-polymerase chain reaction analysis. Adjusted conditional logistic regression was used to estimate the interactions of SNP with quartiles of dietary factors in relation to MetS. MetS was defined by the modified National Cholesterol Education Program/Adult Treatment panel III. RESULTS: Two dietary patterns were extracted. The healthy dietary pattern was loaded heavily on vegetables, legumes, low fat dairy, whole grains, liquid oils and fruits; the western dietary pattern consisted of a high intake of soft drinks, fast foods, sweets, solid oils, red meats, salty snacks, refined grains, high fat dairy, tea and coffee, eggs and poultry. Among A allele carriers, being in the highest quartiles of western dietary pattern score and saturated fatty acid intake had an increased risk of MetS, compared to those in the lowest quartile (P trend = 0.007). Saturated fatty acid intake could modulate the association of A allele carriers of MC4R with MetS (P interaction = 0.03). A significant interaction was observed between rs12970134 with total fat and iron intake on the risk of abdominal obesity (P interaction < 0.05). CONCLUSION: Our findings suggest an interaction between rs12970134 and western dietary pattern, fat and vegetable intakes on the risk of MetS or its components. PMID- 27186235 TI - Price and affordability of direct-acting antiviral regimens for hepatitis C virus in the United States. AB - Hepatitis C virus is a serious infection causing cirrhosis, liver cancer, and death. The recent development of direct-acting antivirals has dramatically improved tolerability of treatment and rates of cure. However, the high price of these medications has often limited access to care and resulted in rationing of medications in the United States to those with advanced liver disease, access to specialist care, and without active substance use. This review assesses the way pharmaceutical prices are established and how pricing of directly acting antiviral regimens in the United States has impacted access to treatment for hepatitis C virus. PMID- 27186236 TI - Optimization and in vitro antiproliferation of Curcuma wenyujin's active extracts by ultrasonication and response surface methodology. AB - BACKGROUND: Curcuma wenyujin, a member of the genus Curcuma, has been widely prescribed for anti-cancer therapy. Multiple response surface optimization has attracted a great attention, while, the research about optimizing three or more responses employing response surface methodology (RSM) was very few. RESULTS: RSM and desirability function (DF) were employed to get the optimum ultrasonic extraction parameters, in which the extraction yields of curdione, furanodienone, curcumol and germacrone from C. wenyujin were maximum. The yields in the extract were accurately quantified using the validated high performance liquid chromatography method with a good precision and accuracy. The optimization results indicated that the maximum combined desirability 97.1 % was achieved at conditions as follows: liquid-solid ratio, 8 mL g(-1); ethanol concentration, 70 % and ultrasonic time, 20 min. The extraction yields gained from three verification experiments were in fine agreement with those of the model's predictions. The surface morphologies of the sonication-treated C. wenyujin were loose and rough. The extract of C. wenyujin presented obvious antiproliferative activities against RKO and HT-29 cells in vitro. CONCLUSION: Response surface methodology was successfully applied to model and optimize the ultrasonic extraction of four bioactive components from C. wenyujin for antiproliferative activitiy.Graphical abstract. PMID- 27186237 TI - Erratum to: Satisfaction with primary care and mental health care among individuals with severe mental illness in a rural area: a seven-year follow-up study of a clinical cohort. AB - [This corrects the article DOI: 10.1186/s13033-016-0064-8.]. PMID- 27186234 TI - Cellular immune response to hepatitis-C-virus in subjects without viremia or seroconversion: is it important? AB - Hepatitis C Virus (HCV) causes chronic infection and represents a global health burden. To date, there is no licensed vaccine for HCV. The high viral replication rate and the existence of several HCV genotypes and quasispecies hamper the development of an effective universal vaccine. In this regard, the current HCV vaccine candidates show genotype-specific protection or narrow cross reactivity against other genotypes. Importantly, HCV spontaneous clearance occurs in 15-50 % of infected subjects, indicating that natural resistance to chronic infection exists. This phenomenon was demonstrated among humans and chimpanzees and continues to motivate researchers attempting to develop an effective HCV vaccine. However, what constitutes a protective immune response or correlate of protection against HCV infection is still vague. Additionally, the mechanisms behind successful HCV clearance suggest the coordination of several arms of the immune system, with cell-mediated immunity (CMI) playing a crucial role in this process. By contrast, although neutralizing antibodies have been identified, they are isolate-specific and poorly correlate with viral clearance. Antigen-specific CD4 T cells, instead, correlate with transient decline in HCV viremia and long lasting control of the infection. Unfortunately, HCV has been very successful in evading host immune mechanisms, leading to complications such as liver fibrosis, cirrhosis and hepatocellular carcinoma. Interestingly, CMI to HCV antigens were shown among exposed individuals without viremia or seroconversion, suggesting the clearance of prior HCV infection(s). These individuals include family members living with HCV-infected subjects, healthcare workers, IV drug users, and sexual contacts. The correlates of protection could be closely monitored among these individuals. This review provides a summary of HCV-specific immune responses in general and of CMI in particular in these cohorts. The importance of these CMI responses are discussed. PMID- 27186240 TI - Dedifferentiated liposarcoma of the adult male breast. AB - A 66-year-old male presented with a right breast mass, enlarging insidiously over a one-year period after trauma to the site. After the findings were attributed to glandular injury and hematoma, the patient eventually underwent mammographic and ultrasonographic evaluation that demonstrated masses in the breast and the axilla. A subsequent ultrasound-guided biopsy of the breast mass yielded a diagnosis of fibromatosis. However, the imaging features were suggestive of malignancy. Surgical resection was performed and revealed dedifferentiated liposarcoma-a neoplasm with components of well- and poorly differentiated liposarcoma as well as nonlipomatous sarcoma. This tumor type is primarily described in the retroperitoneum and limbs and is especially rare in the breast. We report an unusual case of multifocal primary dedifferentiated liposarcoma involving the breast in a man. PMID- 27186238 TI - Decoding the complete arsenal for cellulose and hemicellulose deconstruction in the highly efficient cellulose decomposer Paenibacillus O199. AB - BACKGROUND: The search for new enzymes and microbial strains to degrade plant biomass is one of the most important strategies for improving the conversion processes in the production of environment-friendly chemicals and biofuels. In this study, we report a new Paenibacillus isolate, O199, which showed the highest efficiency for cellulose deconstruction in a screen of environmental isolates. Here, we provide a detailed description of the complex multi-component O199 enzymatic system involved in the degradation of lignocellulose. RESULTS: We examined the genome and the proteome of O199 grown on complex lignocellulose (wheat straw) and on microcrystalline cellulose. The genome contained 476 genes with domains assigned to carbohydrate-active enzyme (CAZyme) families, including 100 genes coding for glycosyl hydrolases (GHs) putatively involved in cellulose and hemicellulose degradation. Moreover, 31 % of these CAZymes were expressed on cellulose and 29 % on wheat straw. Proteomic analyses also revealed a complex and complete set of enzymes for deconstruction of cellulose (at least 22 proteins, including 4 endocellulases, 2 exocellulases, 2 cellobiohydrolases and 2 beta glucosidases) and hemicellulose (at least 28 proteins, including 5 endoxylanases, 1 beta-xylosidase, 2 xyloglucanases, 2 endomannanases, 2 licheninases and 1 endo beta-1,3(4)-glucanase). Most of these proteins were secreted extracellularly and had numerous carbohydrate-binding domains (CBMs). In addition, O199 also secreted a high number of substrate-binding proteins (SBPs), including at least 42 proteins binding carbohydrates. Interestingly, both plant lignocellulose and crystalline cellulose triggered the production of a wide array of hydrolytic proteins, including cellulases, hemicellulases, and other GHs. CONCLUSIONS: Our data provide an in-depth analysis of the complex and complete set of enzymes and accessory non-catalytic proteins-GHs, CBMs, transporters, and SBPs-implicated in the high cellulolytic capacity shown by this bacterial strain. The large diversity of hydrolytic enzymes and the extracellular secretion of most of them supports the use of Paenibacillus O199 as a candidate for second-generation technologies using paper or lignocellulosic agricultural wastes. PMID- 27186241 TI - Radiographic findings of Proteus Syndrome. AB - The extremely rare Proteus Syndrome is a hamartomatous congenital syndrome with substantial variability between clinical patient presentations. The diagnostic criteria consist of a multitude of clinical findings including hemihypertrophy, macrodactyly, epidermal nevi, subcutaneous hamartomatous tumors, and bony abnormalities. These clinical findings correlate with striking radiographic findings. PMID- 27186239 TI - Investigating the effects of copy number variants on reading and language performance. AB - BACKGROUND: Reading and language skills have overlapping genetic bases, most of which are still unknown. Part of the missing heritability may be caused by copy number variants (CNVs). METHODS: In a dataset of children recruited for a history of reading disability (RD, also known as dyslexia) or attention deficit hyperactivity disorder (ADHD) and their siblings, we investigated the effects of CNVs on reading and language performance. First, we called CNVs with PennCNV using signal intensity data from Illumina OmniExpress arrays (~723,000 probes). Then, we computed the correlation between measures of CNV genomic burden and the first principal component (PC) score derived from several continuous reading and language traits, both before and after adjustment for performance IQ. Finally, we screened the genome, probe-by-probe, for association with the PC scores, through two complementary analyses: we tested a binary CNV state assigned for the location of each probe (i.e., CNV+ or CNV-), and we analyzed continuous probe intensity data using FamCNV. RESULTS: No significant correlation was found between measures of CNV burden and PC scores, and no genome-wide significant associations were detected in probe-by-probe screening. Nominally significant associations were detected (p~10(-2)-10(-3)) within CNTN4 (contactin 4) and CTNNA3 (catenin alpha 3). These genes encode cell adhesion molecules with a likely role in neuronal development, and they have been previously implicated in autism and other neurodevelopmental disorders. A further, targeted assessment of candidate CNV regions revealed associations with the PC score (p~0.026-0.045) within CHRNA7 (cholinergic nicotinic receptor alpha 7), which encodes a ligand gated ion channel and has also been implicated in neurodevelopmental conditions and language impairment. FamCNV analysis detected a region of association (p~10( 2)-10(-4)) within a frequent deletion ~6 kb downstream of ZNF737 (zinc finger protein 737, uncharacterized protein), which was also observed in the association analysis using CNV calls. CONCLUSIONS: These data suggest that CNVs do not underlie a substantial proportion of variance in reading and language skills. Analysis of additional, larger datasets is warranted to further assess the potential effects that we found and to increase the power to detect CNV effects on reading and language. PMID- 27186243 TI - Tumor track seeding: A new complication of fiducial marker insertion. AB - In the United States, lung cancer is the leading cause of cancer-related death. Candidates for tumor ablation using CyberKnife(r) require fiducial placement in or near the target tumor to achieve precision. Placing these reference points may lead to complications including pneumothorax and/or hemorrhage. We report a new complication: the appearance of metastatic foci along the track of the fiducial marker. Since the marker was inserted by traversing the original primary tumor, we hypothesize that malignant cells were seeded along the track. In light of this new complication, current techniques for the insertion of fiducial markers should consider a peripheral approach when possible to avoid tracking of malignant cells. PMID- 27186244 TI - Conservatively treated Type B intramural hematoma: Progression into acute aortic dissection followed by spontaneous resolution, assessed by CT. AB - This case report shows the full spectrum evolution of type B intramural hematoma under conservative treatment, with initial progression into a true aortic dissection, followed by extremely rare near-complete healing of the dissection at followup. PMID- 27186242 TI - Primary renal carcinoid tumor: A radiologic review. AB - Carcinoid tumor is the classic famous anonym of neuroendocrine neoplasms. Primary renal carcinoid tumors are extremely rare, first described by Resnick and colleagues in 1966, with fewer than a total of 100 cases reported in the literature. Thus, given the paucity of cases, the clinical and histological behavior is not well understood, impairing the ability to predict prognosis. Computed tomography and (occasionally) octreotide studies are used in the diagnosis and followup of these rare entites. A review of 85 cases in the literature shows that no distinctive imaging features differentiate them from other primary renal masses. The lesions tend to demonstrate a hypodense appearance and do not usually enhance in the arterial phases, but can occasionally calcify. Octreotide scans do not seem to help in the diagnosis; however, they are more commonly used in the postoperative followup. In addition, we report a new case of primary renal carcinoid in a horseshoe kidney. PMID- 27186245 TI - Duodenal lymphangitis carcinomatosa: A rare case. AB - Duodenal lymphangitis carcinomatosa has been sporadically described, and little attention has been paid so far. To our knowledge, no data on radiological findings for this rare entity has been published. We report a case of duodenal lymphangitis carcinomatosa secondary to gallbladder mass in a 44-year-old Indian man to focus on the radiological diagnosis, which was further confirmed by endoscopic-guided biopsy and immunohistochemical analysis. PMID- 27186246 TI - Cavernous hemangioma with extensive sclerosis masquerading as intrahepatic cholangiocarcinoma - A pathologist's perspective. AB - A patient presented with an acute episode of bright red blood in her stool. The incidental liver mass seen in segment 4 was suspected to represent a cholangiocarcinoma due to associated mild intrahepatic biliary ductal dilatation and suspicion for capsular retraction. Pathology confirmed that this lesion represented a sclerosing hemangioma. This case report corroborates prior observations that degenerative changes in hemangiomas-sclerosis, narrowing of vascular channels, thrombosis, infarct, hemorrhage-may produce atypical radiographic findings. Since these atypical radiographic features may suggest a primary or metastatic malignancy, the protean appearance of hemangiomas remains an important consideration in the evaluation of hepatic masses. PMID- 27186247 TI - Femoroacetabular impingement: A classic case of cam-type impingement in a 21-year old soldier. AB - We describe a case of femoroacetabular impingement (FAI) in a 21-year-old male U.S. Army Private. Pre-operative radiographs demonstrated a dysplastic bump at the right head-neck junction. The patient underwent arthroscopy and resection of the bump, resulting in a improved contour of the femoral head-neck junction. After standard recovery, he is now able to ambulate and flex his right hip without pain and has returned to full duty. PMID- 27186248 TI - Breast metastasis in an adult woman with alveolar rhabdomyosarcoma of the ethmoid sinus. AB - A new breast mass was identified in an adult woman undergoing treatment for a known ethmoid sinus alveolar rhabdomyosarcoma. Histopathological evaluation revealed alveolar rhabdomyosarcoma metastatic to the breast. Alveolar rhabdomyosarcoma, primarily described in adolescents and especially rare in adults, can uncommonly metastasize to the breast. PMID- 27186249 TI - Neonatal adenomyomatosis of the gallbladder: An incidental finding at 12 hours of life. AB - Adenomyomatosis of the gallbladder, although relatively common in adults, is a rare entity in the pediatric age group. Controversy still exists as to whether or not to perform followup ultrasound, as there is a questionable increased risk of gallbladder carcinoma in adults. We present a case of neonatal adenomyomatosis that was diagnosed at 12 hours of life in a term newborn. PMID- 27186250 TI - Lumbar spine chordoma. AB - Chordoma is a rare tumor arising from notochord remnants in the spine. It is slow growing, which makes it difficult to diagnose and difficult to follow up after treatment. Typically, it occurs in the base of the skull and sacrococcygeal spine; it rarely occurs in other parts of the spine. CT-guided biopsy of a suspicious mass enabled diagnosis of lumbar spine chordoma. PMID- 27186251 TI - Langerhans cell histiocytosis of the sacrum. AB - Langerhans cell histiocytosis is a rare disease with a wide spectrum of clinical presentations. It is a multisystemic disease with organ system involvement ranging from simple-where it involves only one organ-to widespread progressive disease. Although it can affect any age group, the peak incidence is between 1 and 3 years of age. PMID- 27186253 TI - Radiologic evaluation of postoperative gastropericardial fistula. AB - Laparoscopic Nissen fundoplication is the current standard surgical option for complicated GERD and symptomatic hiatal hernia. Though comparable in safety, short-term efficacy, and patient satisfaction when compared with open operation, laparoscopic Nissen fundoplication has demonstrated shorter hospital stays and recuperative times. Commonly reported complications include gastric or esophageal injury, splenic injury, pneumothorax, bleeding, pneumonia, fever, wound infections, and dysphagia. We present an unusual case of gastropericardial fistula that developed as a late complication of laparoscopic Nissen fundoplication performed 4 years earlier. PMID- 27186254 TI - Migration of trochanteric cerclage cable debris to the knee joint. AB - Migrating orthopedic hardware has widely been reported in the literature. Most reported cases of migrating hardware involve smooth Kirschner wires or loosening/fracture of hardware involved with joint stabilization/fixation. It is unusual for hardware to migrate within the soft tissues. In some cases, smooth Kirschner wires have migrated within the thoracic cage-a proposed mechanism for this phenomenon is the negative intrathoracic pressure. While wires have also been reported to gain access to circulation, transporting them over larger distances, the majority of broken or retained wires remain local. We report a case of a 34-year-old man in whom numerous fragments of braided cable migrated from the hip to the knee. PMID- 27186252 TI - Intrahepatic ovulation. AB - Ectopic ovaries are a rare finding in the literature, with fewer than 50 published cases to date. This phenomenon has been found in the omentum, bladder, mesentery, and uterus; attached to the colon; inside the left labia majora; and in the kidney. Various etiologies have been proposed, including postsurgical or postinflammatory transplantation, malignant origins, and abnormal embryologic development. We report the ultrasonographic, computed tomographic (CT), and magnetic resonance (MR) imaging of, what is to the best of our knowledge, the first case of an intrahepatic ectopic ovary. PMID- 27186255 TI - Morel-Lavallee lesion of the elbow with ultrasound and MRI correlation. AB - Morel-Lavallee lesions are hemolymphatic, nonanatomic fluid collections that result from a separation of the subcutaneous tissue from the underlying fascia. Ultrasound and MRI characteristics of such lesions have been previously described and can be helpful in establishing a diagnosis and guiding clinical management. We present a case of a Morel-Lavallee lesion of the elbow, with ultrasound and MRI correlation, which has not been reported in the radiology literature heretofore. PMID- 27186256 TI - Deep soft-tissue leiomyoma of the forearm mimicking a primary bone tumor of the ulna. AB - Leiomyomas of the soft tissues are rare in general, and extremely uncommon in the forearm. In general, leiomyomas are benign soft-tissue tumors that occur where smooth muscles are present. We present a case of soft-tissue leiomyoma of the forearm eroding the midshaft of the ulna, with emphasis on radiological diagnosis and histopathological correlation. PMID- 27186257 TI - Tuberculous peritonitis. AB - Tuberculous peritonitis is a serious condition with rising prevalence in recent years. It is especially common in those patients with risk factors such as an immunocompromised state, chronic kidney disease, or cirrhosis/liver disease. Spread is typically hematogenous from pulmonary foci. We report on a 34-year-old man who presented with initial complaints of cough, low-grade fevers, abdominal pain, and nausea/vomiting. Chest x-ray showed a cluster of nodular opacities on the right upper lobe, and a CT scan showed diffuse thickening and nodularity of the omentum with prominent mesenteric lymph nodes, consistent with tuberculous peritonitis. PMID- 27186258 TI - Novel, congenital iliac arterial anatomy: Absent common iliac arteries and left internal iliac artery. AB - Congenital anomalies of the iliac arterial system are rare and can be associated with ischemia. With an increase in vascular imaging and interventions, such anomalies are likely to be encountered with greater frequency. We present the case of a 25-year-old female who was incidentally found to have absence of the common iliac arteries bilaterally and the left internal iliac artery, a constellation not previously reported in the literature. We present relevant imaging findings, review embryonic vascular development, and discuss potential clinical implications. PMID- 27186259 TI - Bilateral lower-extremity numbness and ataxia in a young female runner. AB - Inferior vena cava (IVC) absence is thought to have either embryologic or developmental etiologies, depending on the degree of absence. Entire absence of the IVC is thought to be due to embryologic insult, whereas recent studies propose that infrarenal IVC absence is developmental, secondary to perinatal thrombosis. Here we report on an adolescent woman with infrarenal absence of IVC and common iliac veins. Clinically, she presented with bilateral lower-extremity numbness and ataxia following strenuous exercise (running > 1 mile). Symptoms resolved with 30 seconds of rest. Radiographically, MRI revealed extensive collateral vasculature that had developed within the paravertebral soft tissues and epidural space of the spinal canal; these collaterals coursed through the neural foramina and caused moderate stenosis at L4/5 and L5/S1. PMID- 27186260 TI - Multimodal Nonlinear Optical Imaging of Live Cells Using Plasmon-Coupled DNA Mediated Gold Nanoprism Assembly. AB - Multiphoton excitation microscopy techniques are the emerging nonlinear optical (NLO) imaging methods to watch the biological world due its ability to penetrate deep into living tissues. Driven by the need to develop multimodal NLO imaging probe, current article reports the design of DNA-mediated gold nanoprisms assembly based optical antennas to enhance multiphoton imaging capability in biological II window. Reported experimental data show a unique way to enhance second harmonic generation (SHG) and two-photon fluorescence (TPF) properties by several orders of magnitudes via plasmon coupled organization into gold nanoprism assembly structures. Experimental and theoretical modeling data using finite difference time domain (FDTD) simulations indicate that huge enhancement of SHG and TPF properties are mainly due to the electric quadrupole contribution and electric field enhancement. Using 1100 nm biological II window light, reported results demonstrated that antibody conjugated assembly structures are capable of exhibiting highly selective and very bright multimodal SHG and TPF imaging of human Hep G2 liver cancer cells. PMID- 27186261 TI - Human lung cancer-derived microparticles enhanced angiogenesis and growth of hepatoma cells in rodent lung parenchyma. AB - This study tested the hypothesis that human lung cancer-derived microparticles (LcD-MPs) played an important role in tumor angiogenesis and growth. Fischer 344 rats (F344, n=18) were equally categorized into group 1 [Sham Control (3.0 mL normal saline intravenous injection (IV))], group 2 [hepatoma cell line (2.0 x 10(6) cells, IV)], and group 3 [hepatoma cell line + LcD-MPs (3.0 x 10(6), IV)]. Animals were euthanized by day 28 after hepatoma cells transfusion. Our result showed that the gross pathology confirmed growth of hepatoma cell line in lung parenchyma. The size and weight of the lungs were significantly increased in group 2 and further elevated in group 3 than in group 1 (all p<0.001). Histopathological analysis demonstrated that the lung crowded score and number of small vessel exhibited an identical pattern, whereas the number of alveolar sacs showed an opposite pattern compared to that of total lung weight among the three groups (all p<0.0001). The cellular expressions of CD34(+), CXCR4(+), c-Kit(+), CK19(+), VEGF(+) and vimentin+ cells in lung parenchyma exhibited an identical pattern compared to those of total lung weight among all groups (all p<0.001). The protein expressions of apoptotic (Bax, cleaved caspase-3 and c-PARP), fibrotic (Smad3, TGF-beta), and tumor suppression (PTEN) biomarkers showed an identical pattern, whereas that of anti-apoptotic (Bcl-2) and anti-fibrotic (Smad1/5, BMP-2) biomarkers were displayed an opposite pattern compared to that of total lung weight among all groups (all p<0.001). The MPs could enhance angiogenesis and accelerated hepatoma cell growth in rodent lung parenchyma. PMID- 27186262 TI - Overexpression of variant PNPLA3 gene at I148M position causes malignant transformation of hepatocytes via IL-6-JAK2/STAT3 pathway in low dose free fatty acid exposure: a laboratory investigation in vitro and in vivo. AB - Epidemiological survey identified that the variant patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene at I148M position exerts direct effect in promoting hepatocellular carcinoma (HCC) under extraneous oxidative stress by interaction with obesity. However, the mechanism is still unknown. HepG2 cells were overexpressed by transinfection of PNPLA3 with wild-type 148I (PNPLA3(WT)) and mutant 148M (PNPLA3(I148M)), respectively. Variation in metabolic indicators, hepatic steatosis, biological behaviors and signaling molecules related to cancer promotion was measured in hepatocytes using low-dose free fatty acid (FFA) exposure. Effect of PNPLA3(I148M) on xenograft biology and its interaction with dietary obesity were also evaluated in animal study. Cells overexpresssing PNPLA3(I148M) in low-dose FFA incubation showed more proliferation, migration, invasion, and less apoptosis (P<0.05). Low-dose FFA specifically activated JAK2/STAT3 phosphorylation of PNPLA3(I148M) cells via upregulation of interleukin 6. Animal study showed high-fat diet accelerated growth of xenografts derived from PNPLA3(I148M) cells incubated in low-dose FFA. In low oxidative stress, PNPLA3(I148M) initiated the hepatocyte malignant transformation through the activation of inflammation-mediated JAK/STAT pathway. Dietary obesity amplified the growth of tumor from PNPLA3(I148M) cells by interaction with local FFA incubation. Anti-inflammation and weight loss might be potential approaches for preventing HCC in high-risk population carrying PNPLA3 variant. PMID- 27186263 TI - An additive effect of eplerenone to ACE inhibitor on slowing the progression of diabetic nephropathy in the db/db mice. AB - Although blockade of the renin-angiotensin-system (RAS) has become standard therapy for diabetic nephropathy (DN), decline in kidney function towards end stage renal disease is seen in many patients. Elevated plasma aldosterone often accompanies RAS blockade by a phenomenon known as "aldosterone escape" and activates the mineralocorticoid receptor (MR). We therefore examined whether addition of the MR antagonist eplerenone to an ACEI would enhance the efficacy in slowing the progression of DN. Untreated uninephrectomized diabetic db/db mice developed progressive albuminuria and glomerulosclerosis between weeks 18 and 22, associated with decreased number of podocytes and increased renal expression of fibrotic markers. The therapeutic effect of eplerenone at 100 mg/kg BW/d on albuminuria, podocyte injury and renal fibrosis was similar to that of enalapril given alone at maximally effective doses. Adding eplerenone to enalapril resulted in further reduction in these measurements. Renal expressions of TNF-alpha, MCP 1, Nox2 and p47phox and renal TBARS levels, markers of inflammation and oxidative stress, were increased during disease progression in diabetic mice, which were reduced by eplerenone or enalapril given alone and further reduced by the two drugs given in combination. However, there were no treatment related effects on plasma K+. Our results suggest that eplerenone is effective in slowing the progression of DN in db/db mice and that the effect is additive to an ACEI. The addition of an MR antagonist void of effects on plasma K+ to an ACEI may offer additional renoprotection in progressive DN via blocking the effects of aldosterone due to escape or diabetes-induction. PMID- 27186264 TI - Homoharringtonine delivered by high proportion PEG of long- circulating liposomes inhibits RPMI8226 multiple myeloma cells in vitro and in vivo. AB - Multiple myeloma (MM) remains an incurable disease in most patients. Homoharringtonine (HHT) is a natural alkaloid produced by various Cephalotaxus species, and is approved by the United States of America Food and Drug Administration to treat patients with acute and chronic myeloid lymphoma. The aim of this study was to develop the high proportion polyethyleneglycol (PEG) of long circulating HHT liposomes (LCL-HHT-H-PEG) and investigate its therapeutic applicability in vitro and in vivo against RPMI8226 MM. The optimized formulation of LCL-HHT-H-PEG showed a higher association with cytotoxicity against MM RPMI8226 cells than those of low proportion PEG of long-circulating HHT liposomes, liposome-encapsulated-HHT, micelle-HHT, and HHT in vitro. Therapeutic experiments in severe combined immunodeficient mice implanted with MM RPMI8226 cells by the subcutaeous route showed the significant inhibition of tumor growth in LCL-HHT-H-PEG group compared with the HHT group, and other control groups. The analysis of flow cytometry and transmission electron microscopy indicated that LCL-HHT-H-PEG exerted the cytotoxicity against MM by inducing the MM apoptosis in vitro and in vivo. This study suggests that our developed LCL-HHT-H-PEG may be regarded as a promising nano-device to deliver anti-MM drug HHT for treatment of MM patients. PMID- 27186265 TI - Na(+)/Ca(2+) exchanger 1 (NCX-1) mediates the anti-apoptotic effect of Akt1 in neonatal rat cardiomyocytes during ischemia/reperfusion. AB - The purpose of this study was to investigate the anti-apoptotic role of Akt1 gene in neonatal rat cardiomyocytes and the relationship with Na(+)/Ca(2+) exchanger 1 (NCX1) during ischemia/reperfusion (IR). The cultured original rat cardiomyocytes were randomly divided into five groups: normal control group (C group), hypoxia/reoxygenation group (HR group), the control vector pLVX-EGFP-3FLAG group (CV group), the gene pLVX-EGFP-3FLAG-Akt1 transfection group (A group), and Akt1 inhibitor LY294002 group (LY group). Cardiomyocyte vitality was determined using MTT, and the apoptosis was determined by TUNEL to verify the anti-apoptotic role of Akt1. The mRNA levels of Akt1 and NCX1 were determined by RT-PCR, the protein expression of Akt1, p-Akt1, NCX1 and the apoptotic proteins of mitochondrial pathway cytochrome C (Cyto C) and caspase-9 were measured by Western blot. As a result, transfected Akt1 (A group) showed increased myocardial cell viability and reduced apoptosis, with increase in Akt1 expression and decrease in NCX1 expression. The levels of apoptotic proteins Cyto C and caspase-9 also declined. This study demonstrated that lentivirus-mediated transfection of Akt1 played an anti-apoptotic role during IR of rat cardiomyocytes, via inhibition of NCX1 and other mitochondrial proteins. PMID- 27186266 TI - Fabrication and clinical application of easy-to-operate pre-cured CPC/rhBMP-2 micro-scaffolds for bone regeneration. AB - Bone tissue engineering scaffolds loading growth factors have been considered as the most perspective among all bone substitutes, yet little progress of its clinical translation has been made. The concept of "micro-scaffolds" was proposed in this study to provide a trajectory to the clinical translation of porous scaffolds. Combining CPC and rhBMP-2, a pre-cured CPC/rhBMP-2 micro-scaffold has been successfully developed and further applied as an easy-to-operate filler for bone regeneration in a pilot clinical study. The results demonstrated superior overall performances of CPC/rhBMP-2 microffolds to traditional therapies, with not only shortened repairing time and improved repairing qualities, but also the potential in treating fractures that are most challenging for current therapies. This pilot clinical study of CPC/rhBMP-2 microffolds further promoted the clinical translation of porous scaffolds for bone regeneration, and provided new insights for future development of artificial bone substitutes. PMID- 27186267 TI - Early protective role of MST1 knockdown in response to experimental diabetic nephropathy. AB - Diabetic nephropathy (DN) is a progressive kidney disease caused by the damage of capillaries in kidney's glomeruli. Mammalian Sterile 20-like kinase 1 (MST1) has been reported to play an important role in many disease, such as diabetes, cardiac disease and ect. However, the potential role of MST1 pathway in DN has not been fully evaluated. In this study, we hypothesized that MST1 could be involved in DN, and MST1 knockdown would attenuate the DN injury in experimental diabetic nephropathy induced by streptozotocin (STZ). The sieving method was used to generate primary cultures of rat podocytes, and cultured according to the previous reports. The clinical data were analyzed for vein specimens from ESRD. Real-time quantitative PCR was used to examine the mRNA levels. Immuno fluorescence assay was used for primary podocyte in vitro. Lectrophoretic mobility shift assay was used for DNA binding activity of NF-kappaB. HE staining for histological examination and western blot assay for protein expression were employed. The average GBM thickness (GBMT) was measured By using the electron microscopy. In vitro, MST1 level increased significantly in primary rat podocyte cultured in hyperglycemia condition. In vivo experiment, diabetes induced by a single STZ injection (50 mg/kg) in SD rats. Knockdown of MST1 expression by lentiviral mediated gene transfer partly reduced the proteinuria and the level of FASL, and improved the pathological changes of the diabetic kidney. In conclusion, the MST1 could be involved in DN pathogenesis and may serve as the target for development of new therapies for DN. PMID- 27186268 TI - The impact of different methods of DNA extraction on microbial community measures of BALF samples based on metagenomic data. AB - PURPOSE: It is a challenge to find a better microorganisms DNA extraction method for samples taken from the lower airways for metagenomic sequencing, as the concentrations of bacteria in the alveoli and small airways are likely considerably less than that of the mouth or lower digestive tract. Background DNA from the host, and extraction biases can significantly interfere with microbiota assessment and increase the cost of sequencing. This study aimed to develop an optimized DNA extraction method, which would enable a higher concentration of microbial DNA to be extracted from the samples. METHODS: We compared the microbiota profiles of the lower airway communities in twelve individuals with IIP. DNA was extracted using three different extraction methods: QIAamp UCP PurePathogen Blood Kit named kit3 in this study, QIAamp UCP Pathogen Mini Kit named kit2, and QIAamp DNA Microbiome Kit named kit1. DNA libraries were constructed according to the manufacturer's instructions (Illumina). The same workflows from Illumina were used to perform cluster generation, template hybridization, isothermal amplification, linearization, blocking, denaturing, and hybridization of the sequencing primers. Raw data was uploaded to MG-RAST v3 and analyzed. RESULTS: A great number of bacterium inhabits the lower airways of patients with IIP, though there is no airway infection. More bacterium was found in mouth or upper airway. DNA concentrations of DNA samples isolated with kit1 with Benzonase were significantly lower than those isolated with the other two kits for BALF and mouthwash samples. Moreover, the ratio of human genome in clean reads of samples isolated with kit1 with Benzonase was remarkably smaller than those isolated with kit2 and kit3. The relative abundance of total bacteria, the total number of taxa, and the relative abundance of taxa in BALF samples as opposed to mouthwash samples with kit1 were significantly higher than for those extracted the other kits. CONCLUSION: A microbial DNA extraction method with pretreatment of depletion of host nucleic acid by Benzonase can enable a higher yield of microbial DNA from samples with a higher fraction of host cells to be obtained. The lower airways of patients with IIP without airway infection were inhabited by a great number of bacterium. PMID- 27186269 TI - Angiotensin II is related to the acute aortic dissection complicated with lung injury through mediating the release of MMP9 from macrophages. AB - BACKGROUND: Acute aortic dissection (AAD) patients usually show concurrent lung injury mainly featured by hyoxemia. To date, no effective treatment method has been established for the AAD complicated with acute lung injury (ALI). Matrix metalloproteinases (MMPs), especially MMP2 and MMP9, have been considered to be closely related to the onset of aortic disease including AAD. To investigate the roles of MMP in the pathogenesis of AAD complicated with ALI, we determined the expression of MMP2 and MMP9 in serum and lung tissues of AAD patients. In addition, a new rat model of AAD complicated with ALI was established to investigate the pathogenesis of such complicated conditions. METHODS AND RESULTS: Angiotensin II (Ang II) and MMP9 were up-regulated in the AAD complicated with ALI patients compared to those of the AAD without ALI patients, normal individuals and the patients with non-ruptured aneurysm. Besides, massive macrophages with MMP9 expression was noticed in the lung tissues in the AAD complicated with ALI patients. On this basis, AAD complicated with ALI rat model was established based on BAPN feeding and infusion of Ang II. Obvious lung injury was observed in the BAPN+Ang II group compared to that of the BAPN group, together with macrophage accumulation in lung tissues, as well as over-expression of MMP9 in lung tissues. After interference of MMP antagonist, a large number of macrophages were still accumulated in the lung tissues, but the lung injury was obviously attenuated. After the interference of AT1 receptor, the number of macrophages in the lung tissues was obviously decreased and the lung injury was obviously relieved. CONCLUSIONS: Ang II is closely related to the lung injury at the early stage of AAD through mediating the release of MMP9 in the macrophages in the lung tissues. PMID- 27186270 TI - Anesthetic isoflurane attenuates activated microglial cytokine-induced VSC4.1 motoneuronal apoptosis. AB - Isoflurane (ISO) exhibits neuroprotective effects against inflammation and apoptosis. However, the role of ISO in motoneuronal apoptosis induced by activated microglia remains poorly studied. We investigated the protective effects of ISO on the apoptosis of ventral spinal cord 4.1 (VSC4.1) motoneurons induced by lipopolysaccharide (LPS)-activated BV-2 microglia. Results indicated that ISO inhibited NF-kappaB activation and pro-inflammatory cytokine release in LPS-treated BV-2 microglia. Conditioned medium (CM) from activated BV-2 cells treated by ISO directly prevented VSC4.1 motoneurons from LPS-CM-induced neuronal apoptosis, as determined by the following: reductions in caspase-8, caspase-9, and caspase-3 activities; downregulation of pro-apoptotic procaspase-8, cleaved (cl)-caspase-8, procaspase-9, cl-caspase-9, caspase-3, cl-caspase-3, Bid, Bax, and cytochrome c expression; and upregulation of anti-apoptotic Bcl-2 expression in LPS-CM-cultured VSC4.1 motoneurons. Findings demonstrated that ISO inhibits BV 2 microglia activation and alleviates VSC4.1 motoneuronal apoptosis induced by microglial activation. These effects suggest that ISO can be used as an alternative agent for reducing neuronal apoptosis. PMID- 27186271 TI - Evaluation of nestin or osterix promoter-driven cre/loxp system in studying the biological functions of murine osteoblastic cells. AB - OBJECTIVE: To compare Osterix and Nestin-Cre/Loxp system in studying the biological functions of murine osteoblastic cells including primary osteoblasts (OBs) and osteolineage mesenchymal progenitor cells (MPCs). METHODS: We isolated primary osteoblasts (OBs) from neonatal Nestin-cre-R26-loxP-YFP (Nes-OBs) and Osterix-cre-R26-loxP-YFP (Osx-OBs) mice and bone marrow mesenchymal stromal cells (BMMSCs) from the adults (termed as Nes-BMMSCs and Osx-BMMSCs). Then we detected the percentage of YFP(+) subpopulation in Nes/Osx-OBs and the percentage of CD45( )YFP(+) progenitor population in Nes/Osx-BMMSCs and sorted them out (termed as Nes/Osx-YFP(+) OBs and Nes/Osx-CD45(-)YFP(+) MPCs) by using the sorting machine. We also analyzed the expression of surface antigens on Nes/Osx-YFP(+) OBs and Nes/Osx-CD45(-)YFP(+) MPCs by Flow cytometry. PDGF-BB induced proliferation of Nes/Osx-YFP(+) OBs and Nes/Osx-CD45(-)YFP(+) MPCs was measured by H3-Thymidine incorporation assay. We then did OB maturation and mineralization assays of Nes/Osx-YFP(+) OBs and CFU and multi-lineage differentiation assays of Nes/Osx CD45(-)YFP(+) MPCs. RESULTS: YFP(+)% in Nes-OBs and Osx-OBs and CD45(-)YFP(+)% in Nes-BMMSCs and Osx-BMMSCs was respectively 5.56%+/-3.56% (n=5), 10.12%+/-2.7% (n=4), 1.29%+/-0.98% (n=13) and 16.38%+/-6.98% (n=17). Both Nes-YFP(+) OBs and Osx-YFP(+) OBs were positive for CD51. Nes/Osx-CD45(-)YFP(+) MPCs were positive for CD51, CD105 and Sca1, and negative for CD31 and CD45. PDGFR expression in Osx YFP(+) OBs was a bit higher than that in Nes-YFP(+) OBs, and slightly higher in Osx-CD45(-)YFP(+) MPCs than in Nes-CD45(-)YFP(+) MPCs. Proliferation ability of Nes/Osx-YFP(+) OBs increased dramatically after stimulated with PDGF-BB for 48 h, while it was not statistically significant that PDGF-BB induced the increase of proliferation ability in either Nes-CD45(-)YFP(+) MPCs or Osx-CD45(-)YFP(+) MPCs. We observed that no significant difference of OB maturation and mineralization ability existed between Nes-YFP(+) OBs and Osx-YFP(+) OBs, and there was little difference of self-renewal and multi-lineage differentiation potential between Nes-CD45(-)YFP(+) MPCs and Osx-CD45(-)YFP(+) MPCs, either. CONCLUSION: Both Nestin and Osterix could be selected as useful markers for the osteoblastic cells, while Osterix was a prior choice due to larger number of Osterix expressing cells than Nestin-expressing cells in distinct subpopulations of bone forming cells. PMID- 27186272 TI - Enhanced penetration of exogenous EPCs into brains of APP/PS1 transgenic mice. AB - The aim of this study was to investigate the repair function of exogenous Endothelial progenitor cells (EPCs) for brain microvascular damage of the APP/PS1 transgenic mouse model of Alzheimer's disease (AD). This study used a density gradient centrifugation method to isolate mononuclear cells (MNCs) from mouse bone marrow, which were subsequently seeded and cultured. Cells were characterized by morphology and detection of the surface markers CD34 and CD133 at different time points by immunofluorescence (IF) and flow cytometry (FCM). Then, EPCs were transfected with GFP adenoviral vectors (GFP-EPCs). Wild-type (WT) and APP/PS1 transgenic mice both received GFP-EPCs injection through the tail vein, and using a PBS buffer injection as the control. Seven days later, the animals' brain tissue was isolated. Expression of GFP was detected by quantitative polymerase chain reaction (qPCR) and western-blot (WB), while the fluorescence of GFP within the brains of mice was observed under a fluorescence microscope. Higher mRNA and protein expression of GFP, accompanied with increased green fluorescence, were detected in the brain of GFP-EPCs-injected APP/PS1 mice, as compared with GFP-EPCs-injected WT mice. The results show that the APP/PS1 transgenic mouse model of AD exhibited enhanced penetration of exogenous EPCs into brains than the WT mice. PMID- 27186273 TI - microRNA-141 inhibits thyroid cancer cell growth and metastasis by targeting insulin receptor substrate 2. AB - microRNA-141 (miR-141), a member of the miR-200 family, and has been reported to involve in tumor initiation and development in many types of cancers. However, the function and underlying molecular mechanism of miR-141 in thyroid cancer remains unclear. Therefore, the aim of this study is to identify its expression, function, and molecular mechanism in thyroid cancer. In this study, we found that miR-141 expression levels were downregulated in human thyroid cancer specimens compared to the adjacent normal tissues, and its expression were strongly correlated with clinical stages and lymph node metastases. Function assays showed that overexpression of miR-141 inhibited cell proliferation, induced cell apoptosis, and decreased migration, invasion in thyroid cancer cells, as well as tumor growth in nude mice. Moreover, insulin receptor substrate 2 (IRS2), a known oncogene, was confirmed as a direct target of miR-141, and IRS2 expression levels were upregulated in thyroid cancer, and its expression were inversely correlated with miR-141 expression levels in human thyroid cancer specimens. Forced expression of IRS2 reversed the inhibition effect induced by miR-141 overexpression in thyroid cancer cells. Taken together, our study provides the first evidence that miR-141 suppressed thyroid cancer cell growth and metastasis through inhibition of IRS2. Thus, miR-141 might serve as a promising therapeutic strategy for thyroid cancer treatment. PMID- 27186274 TI - MicroRNA-217 inhibits cell proliferation and invasion by targeting Runx2 in human glioma. AB - MircroRNA-217 (miR-217) has been showed to involve in the initiation and development of human cancers, and is recognize as a tumor suppressor miRNA in several tumors. However, the clinical significance and its underlying role in human glioma remain unclear. Herein, we found that the expression of miR-217 was significantly down-regulated in glioma tissues as compared with adjacent normal brain tissues. Clinical association analysis disclosed that low-expression of miR 217 was evidently negative associated with advanced tumor stage (grade III + IV) in glioma. Further function assays showed that miR-217 inhibited proliferation, colony formation, invasion and migration of glioma cells. Notably, runt-related transcription factors 2 (Runx2) was identified as a functional target of miR-217 in glioma. Furthermore, an inverse correlation between miR-217 and Runx2 expression was observed in glioma tissues. Downregulation of Runx2 has similar with inhibition effect of overexpression of miR-217, and upregulation of Runx2 reversed the effects of overexpressing of miR-217. Taken together, these results suggest a critical role of miR-217 in suppressing proliferation, migration, and invasion of glioma by targeting Runx2. PMID- 27186275 TI - miR-132 targeting E2F5 suppresses cell proliferation, invasion, migration in ovarian cancer cells. AB - Accumulating evidence showed that microRNA-132 (miR-132) are involved in development and progression of several types of cancers, however, the function and underlying molecular mechanism of miR-132 in ovarian cancer remains unclear. In this study we investigated the biological roles and molecular mechanism of miR 132 in ovarian cancer. Here, we found that that the expression levels of miR-132 were dramatically decreased in ovarian cancer cell lines and clinical ovarian cancer tissue samples. Then, we found that introduction of miR-132 significantly suppressed the proliferation, colony formation, migration and invasion of ovarian cancer cells. Mechanism investigation revealed that miR-132 inhibited the expression of transcription factor E2F5 by specifically targeting its mRNA 3'UTR. Moreover, the expression level of E2F5 was significantly increased in ovarian cancer tissues than in the adjacent normal tissues, and its expression was inversely correlated with miR-132 expression in clinical ovarian cancer tissues. Additionally, silencing E2F5 was able to inhibit the proliferation, colony formation, migration and invasion of ovarian cancer cells, parallel to the effect of miR-132 overexpression on the ovarian cancer cells. Meanwhile, overexpression of E2F5 reversed the inhibition effect mediated by miR-132 overexpression. These results indicate that miR-132 suppresses the cell proliferation, invasion, migration in ovarian cancer cells by targeting E2F5. PMID- 27186276 TI - Methylation-mediated loss of SFRP2 enhances melanoma cell invasion via Wnt signaling. AB - Wnt signaling plays an essential role in the initiation and progression of melanoma tumors. The Secreted Frizzled Related Proteins (SFRPs) are a family of proteins that suppress Wnt signaling. The methylation of SFRPs reduces their activity, and hence augments Wnt signaling. However, whether the methylation of SFRP2, a member of SFRPs, may be involved in the pathogenesis of melanoma is not known. Here we investigated the expression levels of SFRP2 in melanoma specimens. We found that SFRP2 mRNA wassignificantly decreased and methylation of SFRP2 gene was significantly increased in malignant melanoma tumors ascompared to the paired adjacent non-tumor tissue. Moreover, SFRP2 expression was significantly decreased in the malignant melanoma celllines, HTB63, A2058 and A375, but not in the non transformed melanocyte cell line, Hermes 3A. The demethylation of SFRP2 gene by 5'-aza-deoxycytidine (5-aza-dCyd) in melanoma cell lines restored SFRP2 expression, at both mRNA and protein levels, and suppressed cell invasion. Furthermore, the demethylation of SFRP2 geneappeared to inhibit nuclear retention of a key Wnt signaling factor, beta-catenin, in melanoma cell lines. Together, these data suggest that SFRP2may function as a melanoma invasion suppressor byinterfering with Wnt signaling, and the methylation of SFRP2 gene may promote pathogenesis of melanoma. PMID- 27186277 TI - Diaphragm contractile dysfunction causes by off-target low-dose irradiation. AB - BACKGROUND: Diaphragm is a primary inspiratory muscle and often receives off target dose in patients with thoracic radiotherapy, and whether acute effect of low dose irradiation would cause contractile dysfunction of the diaphragm remains unclear. We use a rat model to investigate the effect of low-dose irradiation on diaphragm contractile function in the current study. METHODS: The radiation dose distributions in patients with esophageal cancer receiving radiotherapy were calculated to determine the dose received by the off-target diaphragm area. Rats were randomly assigned to an irradiated or a non-irradiated control group (n = 10 per group). A single-fraction of 5 Gy radiation was then delivered to the diaphragms of Sprague-Dawley rats in the irradiated group. The control group received sham irradiation (0 Gy). Rats were sacrificed 24 hours after the irradiation procedures and diaphragms were removed en bloc for contractile function assessment, oxidative injury and DNA damage analysis. Oxidative injury was determined by analyzing concentration of protein carbonyls and DNA damage was determined by analyzing retention of gammaH2AX foci in nuclei of diaphragmatic tissue. RESULTS: At 24 hours after delivery of a single dose of 5 Gy radiation, specific twitch (p = 0.03) and tetanus tension (p = 0.02) were significantly lower in the irradiated group than in the control group. The relative force frequency curves showed a significant downward shift in the irradiated group. Protein carbonyl level (p < 0.01) and percentage of gammaH2AX-positive diaphragm muscle cells were significantly higher in the irradiated group than in the control group 24 hours after irradiation (58% vs. 30%, p = 0.01). CONCLUSIONS: Off-target low dose irradiation could induce acute contractile dysfunction of the diaphragm which was related to radiation-induced direct DNA and indirect oxidative damage. PMID- 27186278 TI - EphA2 silencing promotes growth, migration, and metastasis in salivary adenoid cystic carcinoma: in vitro and in vivo study. AB - EphA2 is associated with tumor growth and distant metastasis in numerous human tumors. Considering the controversial effects of EphA2 in different tumors and the lack of reports in salivary adenoid cystic carcinoma (SACC), we evaluated the effects of EphA2 inhibition by short hairpin RNA on SACC through in vivo and in vitro researches for the first time. Real-time reverse transcriptase-PCR and western blot analysis were conducted to verify the interference effect on SACC cells. Using Cell Counting Kit-8, wound healing, Transwell and Matrigel adhesion assays, we confirm that inhibition of EphA2 promotes the migration, invasion and adhesion ability of SACC cells. In vivo research, we prove that silencing of EphA2 significantly accelerates tumor growth and lung metastasis ability by establishing xenograft models in mice, including subcutaneous inoculation and tail vein injection. In addition, immunostaining of EphA2, E-cadherin and Slug from 40 specimens and in vitro simulation of perineural invasion (PNI) assay imply that suppression of EphA2 partially contribute to epithelial-mesenchymal transition and enhancement of PNI in SACC. In conclusion, all the data suggest that EphA2 may act as a tumor suppressor in SACC progression. PMID- 27186279 TI - Restoration of murine femoral segmental defect using CTGF-overexpressing MC3T3-E1 cells. AB - Connective tissue growth factor (CTGF) is a member of the CCN super family and is reported to widely participate in bone development and regeneration. This study aimed to restore murine femoral segmental defect using CTGF-overexpressing MC3T3 E1 cells. MC3T3-E1 cells were transinfected by lenti-CTGF (LvCTGF) and lenti negative control (LvNC) virus to obtain stably transinfected cells. Real-time PCR, Western blot, alkaline phosphatase activity assay, and alizarin red staining demonstrated that the overexpression of CTGF enhanced osteogenesis in vitro. Cell migration assay results showed that LvCTGF cells expressed higher migration ability than LvNC cells, while CCK-8 assay revealed no significant difference in cell proliferation. The LvCTGF and LvNC cells were then seeded into a chitosan/beta-TCP scaffold and were used to restore a murine femoral segmental defect. Samples were harvested by the end of 2 and 5 weeks respectively. Micro-CT analysis and Masson's trichrome staining results showed that the LvCTGF-scaffold group expressed better bone healing compared with the LvNC-scaffold and scaffold only groups. CTGF-overexpressed cells serve as an efficient source of seeding cells for bone regeneration. PMID- 27186280 TI - Bone marrow derived mesenchymal stem cells alleviated brain injury via down regulation of interleukin-1beta in focal cerebral ischemic rats. AB - Interleukin-1beta (IL-1beta) plays an important role in brain injury after focal ischemia, and bone marrow-derived mesenchymal stem cells (BMSCs) are capable of reducing the expression of IL-1beta, we investigated the effects of BMSCs transplantation on brain edema and cerebral infarction as well as the underlying mechanisms via IL-1beta. Male Sprague-Dawley rats were randomly divided into five groups: Normal + phosphate-buffered saline (PBS), middle cerebral artery occlusion (MCAO) + PBS, Normal + BMSCs, MCAO + BMSCs and MCAO + IL-1ra (an antagonist of IL-1beta). BMSCs were transplanted 24 hours after MCAO, and brain edema was evaluated by Magnetic Resonance Imaging (MRI) and brain water content method after BMSCs transplantation. The expression of NeuN and AQP4 was analyzed by immunofluorescence staining. Protein level of AQP4 and IL-1beta was detected by western blot analysis 48 hours after transplantation. The results showed that BMSCs transplantation reduced brain edema by measurement of brain water content and ADC Value of MRI, as well as the expression of AQP4 and IL-1beta. It was also found that BMSCs transplantation could alleviate the cerebral infarction volume and neuronal damage. Both the brain edema and the cerebral infarction were associated with IL-1beta expression. In conclusion, BMSCs transplantation was capable of alleviating brain edema as well as reducing cerebral infarction via down-regulation of IL-1beta expression, thus repair the injured brain in focal cerebral ischemic rats. PMID- 27186281 TI - Deregulation of MicroRNA-375 inhibits cancer proliferation migration and chemosensitivity in pancreatic cancer through the association of HOXB3. AB - BACKGROUND: The expression pattern and regulatory effect of microRNA-375 (miR 375) in human pancreatic cancer was explored. METHODS: Gene expression of miR-375 was compared between pancreatic tumors and non-tumorous pancreatic tissues, as well as pancreatic cancer cell lines and normal epithelial cells. MiR-375 was downregulated in pancreatic cancer cell lines, Capan-1 and PANC-1 cells, to assess possible tumor suppressive effects on cancer proliferation, migration, cisplatin chemosensitivity and in vivo growth of tumor explant. The regulation of miR-375 on its target gene, homeobox B3 (HOXB3) gene, was assessed though luciferase activity assay and qRT-PCR. HOXB3 was also downregulated in Capan-1 and PANC-1 cells to assess its functional correlation with miR-375 on cancer regulation. RESULTS: MiR-375 was upregulated in pancreatic tumors and pancreatic cancer cell lines. MiR-375 downregulation had tumor suppressive effects in Capan 1 and PANC-1 cells by reducing cancer proliferation & migration, increasing cisplatin sensitivity and inhibiting in vivo tumor explant growth. HOXB3 was directly bound by miR-375, and was negatively regulated by miR-375 in pancreatic cancer cells. Subsequent HOXB3 downregulation reversed the suppression of miR-375 downregulation on cancer proliferation, migration and cisplatin chemosensitivity in pancreatic cancer. CONCLUSION: MiR-375 is an oncogene in pancreatic cancer. Deregulation of miR-375 is inhibitory to the development of pancreatic cancer, and reversely regulated by HOXB3. PMID- 27186282 TI - Privacy and security in the era of digital health: what should translational researchers know and do about it? AB - The rapid growth in the availability and incorporation of digital technologies in almost every aspect of our lives creates extraordinary opportunities but brings with it unique challenges. This is especially true for the translational researcher, whose work has been markedly enhanced through the capabilities of big data aggregation and analytics, wireless sensors, online study enrollment, mobile engagement, and much more. At the same time each of these tools brings distinctive security and privacy issues that most translational researchers are inadequately prepared to deal with despite accepting overall responsibility for them. For the researcher, the solution for addressing these challenges is both simple and complex. Cyber-situational awareness is no longer a luxury-it is fundamental in combating both the elite and highly organized adversaries on the Internet as well as taking proactive steps to avoid a careless turn down the wrong digital dark alley. The researcher, now responsible for elements that may/may not be beyond his or her direct control, needs an additional level of cyber literacy to understand the responsibilities imposed on them as data owner. Responsibility lies with knowing what you can do about the things you can control and those you can't. The objective of this paper is to describe the data privacy and security concerns that translational researchers need to be aware of, and discuss the tools and techniques available to them to help minimize that risk. PMID- 27186283 TI - Barcoded sequencing reveals diverse intrauterine microbiomes in patients suffering with endometrial polyps. AB - Results of this study showed that the bacterial composition in vagina (V) greatly differed from intrauterine microbiome (I). Microbiomes were present in all intrauterine samples of healthy women (Group H (I)) and patients with endometrial polyps (EP) (including Group EP (I) and Group EP/chronic endometritis (CE) (I)). Indeed, the intrauterine bacteria population in Group EP/CE (I) were more diverse than those in Groups EP (I) and H (I). The result also confirmed the bacterial composition differences between vagina and uterus as well as the intrauterine microbiome alteration in the patients, compared to the healthy. Although bacteria of Proteobacteria, Firmicutes and Actinobacteria, dominated the intrauterine microbiome in all samples, however, proportions of Firmicutes from Group EP/CE (I) and Group EP (I) were much higher than that from Group H (I), in contrast, the proportions of Proteobacteria were far lower than the healthy. At the genus level, compared to Group H (I), it is found that proportions of Lactobacillus, Gardnerella, Bifidobacterium, Streptococcus, and Alteromonas were significantly higher, and that of Pseudomonas were significantly lower in Group EP/CE (I) or Group EP (I). In addition, lower proportions of Enterobacter and Sphingomonas and a higher proportion of Prevotella were also observed in Group EP/CE (I). In conclusion, uterine microbiomes between patients with EP and the healthy are significantly different and all the potentially important variation of uterine microbes may cause EP, but not definitively related to CE. Further experiments should be performed to test these relationships to endometritis occurrence. PMID- 27186284 TI - The combination of tacrolimus and entecavir improves the remission of HBV associated glomerulonephritis without enhancing viral replication. AB - BACKGROUND: Tacrolimus inhibits hepatitis B virus entry into hepatocytes through targeting the HBV receptor, sodium taurocholate cotransporting polypeptide. This study was performed to evaluate the efficacy and safety of Tacrolimus combined with entecavir antiviral therapy for HBV-associated glomerulonephritis patients with biopsy-proven membranous nephropathy. METHOD: A cohort of 42 patients was enrolled in this retrospective study. Twenty-three patients received Tacrolimus (0.05 mg/kg/day) in combination entecavir over 24 weeks, whereas the other 19 patients only received entecavir monotherapy. RESULTS: The probability of proteinuria remission in the Tacrolimus+entecavir group was 69 and 87% after 12 and 24 weeks, whereas was only 26 and 42%, respectively, in the entecavir group. The mean time to partial or complete remission was 18.6 weeks in the Tacrolimus+entecavir group and 34.3 weeks in the entecavir group (P<0.001). A decrease in the HBV DNA titer was observed in all patients with active HBV replication. None of the HBV carriers in the Tacrolimus+entecavir group showed evidence of HBV reactivation. The serum creatinine and alanine aminotransferase levels remained stable in both groups. The Tacrolimus target trough concentration was 5-10 ng/mL. CONCLUSION: Tacrolimus combined with entecavir rapidly and effectively induced remission of HBV-GN in Chinese adults. Furthermore, Tacrolimus may have a synergistic antiviral effect with entecavir. PMID- 27186286 TI - Houttuynia cordata Thunb reverses oxaliplatin-induced neuropathic pain in rat by regulating Th17/Treg balance. AB - Oxaliplatin is a widely used anti-advanced colorectal cancer drug, while it could induce neuropathy. Houttuynia cordata Thunb (HCT) has a wide range of biological activities, such as anti-inflammation, anti-cancer, and immune regulation. In the present study, we investigated the effect of HCT on oxaliplatin-induced neuropathy in rat models. HCT (1000 mg/kg/day) significantly decreased the number of withdrawal responses and the withdrawal latency in oxaliplatin-treated rats. HCT could down-regulated the serum levels of Interleukin-6 (IL-6) and macrophage inflammatory protein1-alpha (MIP-1alpha) in oxaliplatin-treated rats. Th17/Treg balance was reversed by HCT in oxaliplatin-treated rats by regulating PI3K/Akt/mTOR signaling pathway. The present results suggest that HCT is useful as a therapeutic drug for oxaliplatin-induced neuropathic pain. PMID- 27186285 TI - Effect of the BRCA1-SIRT1-EGFR axis on cisplatin sensitivity in ovarian cancer. AB - There is accumulating evidence that breast cancer 1 (BRCA1), sirtuin 1 (SIRT1), and epidermal growth factor receptor (EGFR) help to modulate cisplatin cytotoxicity. The role of dynamic crosstalk among BRCA1, SIRT1, and EGFR in cisplatin sensitivity remains largely unknown. We found that BRCA1, SIRT1, and EGFR levels were increased in cisplatin-resistant ovarian cancers compared with those in cisplatin-sensitive ovarian cancers. Hypomethylation in the BRCA1 promoter was associated with BRCA1 activation, significantly elevated SIRT1 levels, decreased nicotinamide adenine dinucleotide (NAD)-mediated SIRT1 activity, and decreased EGFR levels. Treatment with 5 and 10 MUg/ml cisplatin induced a gradual increase in BRCA1 and SIRT1 levels and a gradual decrease in NAD levels and NAD-mediated SIRT1 activity, whereas EGFR levels were increased or decreased by treatment with 5 or 10 MUg/ml cisplatin, respectively. The overexpression of SIRT1 or the enhancement of SIRT1 activity synergistically enhanced the BRCA1-mediated effects on EGFR transcription. In contrast, the knockdown of SIRT1 or the inhibition of SIRT1 activity inhibited the BRCA1 mediated effects on EGFR transcription. BRCA1 regulates EGFR through a BRCA1 mediated balance between SIRT1 expression and activity. Those results improve our understanding of the basic molecular mechanism underlying BRCA1-related cisplatin resistance in ovarian cancer. PMID- 27186288 TI - Over-expression of HSPA12B protects mice against myocardium ischemic/reperfusion injury through a PPARgamma-dependent PI3K/Akt/eNOS pathway [Retraction]. AB - [This retracts the article on p. 2724 in vol. 7, PMID: 26885270.]. PMID- 27186287 TI - CMD kinetics and regenerative medicine. AB - The author's theory of the cell memory disc (CMD) offers a radical and holistic picture of the cell from both functional and structural perspectives. Despite all of the attention that has been focused on different regenerative strategies, several serious CMD-based obstacles still remain that make current cell therapies inherently unethical, harmful, and largely ineffective from a clinical viewpoint. Accordingly, unless there is a real breakthrough in finding an alternative or complementary approach to overcome these barriers, all of the discussion regarding cell-based therapies may be fruitless. Hence, this paper focuses on the issue of CMD kinetics in an attempt to provide a fresh perspective on regenerative medicine. PMID- 27186289 TI - NPGPx (GPx7): a novel oxidative stress sensor/transmitter with multiple roles in redox homeostasis. AB - NPGPx (GPx7) is a member of the glutathione peroxidase (GPx) family without any GPx activity. GPx7 displays a unique function which serves as a stress sensor/transmitter to transfer the signal to its interacting proteins by shuttling disulfide bonds in response to various stresses. In this review, we focus on the exceptional structural and biochemical features of GPx7 compared to other 7 family members and described how GPx7 regulates the diverse signaling targets including GRP78, PDI, CPEB2, and XRN2, and their different roles in unfolded protein response, oxidative stress, and non-targeting siRNA stress response, respectively. The phenotypes associated with GPx7 deficiency in mouse or human including ROS accumulations, highly elevated cancer incidences, auto immune disorders, and obesity are also revealed in this paper. Finally, we compare GPx8 with GPx7, which shares the highest structural similarity but different biological roles in stress response. These insights have thus provided a more comprehensive understanding of the role of GPx7 in the maintenance of redox homeostasis. PMID- 27186290 TI - Galectin-1 mediates TGF-beta-induced transformation from normal fibroblasts into carcinoma-associated fibroblasts and promotes tumor progression in gastric cancer. AB - Rcinoma-associated fibroblasts (CAFs) are a major constituent of the tumor microenvironment. Cancer cells can induce the transformation from normal fibroblasts (NFs) into CAFs, reciprocally, CAFs promote tumor invasion and proliferation. TGF-beta has been the mostly accepted factor to fuel NFs transformation into CAFs. Galectin-1 (Gal1) is highly upregulated in CAFs of multiple human cancers, and overexpression of Gal1 in CAFs promotes tumor progression. The effect of Gal1 on TGF-beta-induced CAFs activation has not yet been established in gastric cancer (GC). In this study, we show that Gal1 expression in stroma is positively related to TGF-beta in epithelial cells by retrospective analysis of GC patient samples. Meanwhile, conditioned media (CMs) from gastric cancer cells induce expression of both Gal1 and the CAFs marker alpha smooth muscle actin (alpha-SMA) in NFs via TGF-beta secretion. Knockdown of Gal1 prevents TGF-beta-induced the conversion of NFs to CAFs. CMs from fibroblasts overexpressing Gal1 inhibits cancer cells apoptosis, promotes migration and invasion in vitro. Thus, Gal1 is significantly involved in the development of tumor-promoting microenvironment by enhancing TGF-beta signaling in a positive feedback loop. Targeting Gal1 in tumor stroma should be considered as a potential therapeutic target for GC. PMID- 27186293 TI - The therapeutic response of CDDO-Me in the esophageal squamous cell carcinoma (ESCC) cells is mediated by CaMKIIalpha. AB - CDDO-Me has exhibited a potent anticancer effect in human esophageal squamous cell carcinoma (ESCC) cells in our previous study, but the molecular interactome remains elusive. We applied the approach of stable-isotope labeling by amino acids in cell culture (SILAC) to assess the proteomic responses of CDDO-Me treatment in human ESCC Ec109 cells. The data were subsequently validated using Western blot assay. The results of our study revealed that CDDO-Me increased the expression level of 543 protein molecules, but decreased the expression level of 709 protein molecules in Ec109 cells. Among these modulated protein molecules, calcium/calmodulin-dependent protein kinase type II subunit alpha (CaMKIIalpha) was highly expressed in all tested ESCC cell lines, whereas its expression levels were substantially lower in normal control cell line. Its silencing by small interfering RNA inhibited CDDO-Me induced apoptosis and autophagy in ESCC cells. Collectively, these data demonstrate that the therapeutic response of CDDO-Me in the human ESCC cells is mediated by CaMKIIalpha. PMID- 27186292 TI - Electrospun nanofibrous sheets of collagen/elastin/polycaprolactone improve cardiac repair after myocardial infarction. AB - Electrospun nanofibrous sheets get increasing attention in myocardial infarction (MI) treatment due to their good cytocompatibility to deliver transplanted stem cells to infarcted areas and due to mechanical characteristics to support damaged tissue. Cardiac extracellular matrix is essential for implanted cells since it provides the cardiac microenvironment. In this study, we hypothesized high concentrations of cardiac nature protein (NP), namely elastin and collagen, in hybrid polycaprolactone (PCL) electrospun nanofibrous sheets could be effective as cardiac-mimicking patch. Optimal ratio of elastin and collagen with PCL in electrospun sheets (80% NP/PCL) was selected based on cytocompatibility and mechanical characteristics. Bone-marrow (BM) c-kit(+) cells anchoring onto NP/PCL sheets exhibited increased proliferative capacity compared with those seeded on PCL in vitro. Moreover, we examined the improvement of cardiac function in MI mice by cell-seeded cardiac patch. Green Fluorescent Protein (GFP)-labeled BM c kit(+) cells were loaded on 80% NP/PCL sheets which was transplanted into MI mice. Both 80% NP/PCL and c-kit(+)-seeded 80% NP/PCL effectively improved cardiac function after 4 weeks of transplantation, with reduced infarction area and restricted LV remodeling. C-kit(+)-seeded 80% NP/PCL was even superior to the 80% NP/PCL alone and both superior to PCL. GFP(+) cells were identified both in the sheets and local infarcted area where transplanted cells underwent cardiac differentiation after 4 weeks. To the best of our knowledge, this is the first report that sheets with high concentrations of nature proteins loaded with BM c kit(+) cells might be a novel promising candidate for tissue-engineered cardiac patch to improve cardiac repair after MI. PMID- 27186291 TI - miR-3646 promotes cell proliferation, migration, and invasion via regulating G2/M transition in human breast cancer cells. AB - MicroRNAs (miRNAs) are small non-coding RNAs that are often located in genomic breakpoint regions and play a critical role in regulating a variety of the cellular processes in human cancer. miR-3646 has been reported to take part in tumorigenic progression in breast and bladder cancer, but its potential functions and exact mechanistic roles in breast cancer are still unclear. The objective of this study was to investigate the role of miR-3646 in breast cancer growth and metastasis using both bioinformatic and experimental approaches. Before starting the bench work, we conducted a bioinformatic study to predict the target genes regulated by miR-3646 using a panel of different algorithms. The results showed that miR-3646 might regulate a large number of genes that are related to cell growth, proliferation, metabolis, transport, and apoptosis and some were cancer related genes. We found that the expression level of miR-3646 was significantly upregulated in breast cancer cells and tissues compared with normal breast cells and no tumor tissues. Subsequently, the MTT and colony formation assay results showed that up-regulation of miR-3646 promoted the cell viability and proliferation. Our results also showed that down-regulation of miR-3646 arrested the cells in G2/M phase in MCF7 and MDA-MB-231 cells which was accompanied by the down-regulation of CDK1/CDC2 and cyclin B1 and upregulation of p21Waf1/Cip1, p27 Kip1, and p53, suggesting that down-regulation of miR-3646 induces G2/M arrest through activation of the p53/p21/CDC2/cyclin B1 pathway. In addition, overexpression of miR-3646 promoted migration and invasion of MCF7 and MDA-MB-231 cells. Taken together, miR-3646 is a potential oncogene in breast cancer and it may represent a new niomarker in the diagnosis and prediction of prognosis and therapeutic response. PMID- 27186294 TI - The antitumor activity study of ginsenosides and metabolites in lung cancer cell. AB - Ginseng and its components exert various biological effects, including antioxidant, anti-carcinogenic, anti-mutagenic, and antitumor activity. Ginsenosides are the main biological components of ginseng. Protopanaxadiol (PPD) and protopanaxatriol (PPT) are two metabolites of ginsenosides. However, the difference between these compounds in anti-lung cancer is unclear. The present study aimed to evaluate the antitumor activity of PPD, PPT, Ginsenosides-Rg3 (G Rg3) and Ginsenosides-Rh2 (G-Rh2) in lung cancer cell. After treatment with cisplatin, PPD, PPT, G-Rg3 or G-Rh2, the viability, apoptosis level and invasiveness of lung cell lines (A549 cell, a lung adenocarcinoma cell line and SK-MES-1 cell, a lung squamous cell line) in vitro were analyzed by Cell Counting Kit-8 (CCK8), Annexin V/PI apoptosis and Matrigel invasion assays, respectively. Here we found that all these compounds led to significant decreases of viability and invasiveness and an obvious increase of apoptosis of A549 and SK-MES-1 cells. Among these, the viability of SK-MES-1 cell treated with PPT was decreased to 66.8%, and this effect was closest to Cisplatin. G-Rg3 had the highest stimulatory effect on apoptosis, and PTT had the highest inhibitory effect on cell invasiveness in A549 and SK-MES-1 cells. These results indicate that both ginsenosides and two metabolites have antitumor activity on lung cancer cell in vitro. However, PPT is more powerful for inhibiting the viability and invasiveness of lung cancer cell, especially lung squamous cell. G-Rg3 has the best pro-apoptosis effects. This study provides a scientific basis for potential therapeutic strategies targeted to lung cancer by further structure modification. PMID- 27186295 TI - CXCL12/CXCR4 axis induces proliferation and invasion in human endometrial cancer. AB - OBJECTIVE: Since that we have previously found CXCL12/CXCR4, an important biological axis is highly transcribed in several cancer cells. We aim to investigate whether CXCL12/CXCR4 axis regulates critical processes in neoplastic transformation that affects endometrial cancer cell biology. METHODS: The expression levels of CXCR4 were analyzed in human normal endometrial tissue, simple hyperplasia, atypical hyperplasia and endometrial cancer cells by immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT PCR). Serum CXCL12 was measured by Enzyme-Linked Immunosorbent Assay (ELISA) in Ishikawa endometrial cancer cell line. To study the biological function of CXCL12/CXCR4 in endometrial cancer, short interfering RNA silencing of CXCR4 was established to analyze the roles of CXCL12/CXCR4 in proliferation, migration, invasion and apoptosis of Ishikawa cells in vitro. RESULTS: The expression level of CXCR4 in endometrial cancer tissue was higher as compared to atypical hyperplasia, simple hyperplasia and normal cycling endometrium cells. Ishikawa cells secreted CXCL12 spontaneously and continuously for 96 hrs in culture. The proliferation, migration and invasion of Ishikawa cells was significantly induced, and the apoptosis was significantly reduced by CXCL12 in combination with CXCR4. Moreover, CXCR4 silencing could significantly antagonize all these functions. CONCLUSIONS: CXCL12/CXCR4 axis plays an important role in the proliferation, invasion and metastasis of endometrial cancer, indicating that CXCR4 could be the target for the treatment of endometrial cancer. PMID- 27186296 TI - The role of JAK/STAT3 signaling pathway on apoptosis of lung adenocarcinoma cell line PC-9 induced by icotinib. AB - OBJECTIVE: The aim of this study is to estimate the role of JAK/STAT3 signaling pathway on apoptosis of lung adenocarcinoma induced by icotinib. METHODS: EGFR mutation was detected in lung adenocarcinoma cell line PC-9 by ARMS assay; The inhibitory rates of cell proliferation of PC-9 cells which were exposed to different concentrations of icotinib (0~100 MUMol/L) for different time (24~72 h) respectively were evaluated by MTT assay; Apoptosis of PC-9 cells exposed to different concentrations of icotinib (0, 0.1, 1 and 10 MUMol/L) for 48 h were evaluated by TUNEL assay; JAK2, STAT3, Bcl-2, Bax mRNA expressions were evaluated by Real-time PCR assay; The protein levels of P-STAT3 and IL-6 were evaluated by Western-blot assay. RESULTS: Human lung adenocarcinoma cell line PC-9 had an exon 19 deletion mutation in EGFR gene; Followed by treatment of icotinib, the proliferation of PC-9 cells were all inhibited significantly, especially in 48 and 72 h (P<0.01) in all concentrations; The inhibitory rates of cell proliferation in different treating time had statistical significance (P<0.01); Cell apoptosis in different concentrations were increased significantly (P<0.05); Along with the increasing concentrations, gene expression levels of JAK2, STAT3 and Bcl-2 decreased significantly (P<0.05), Bax increased significantly (P<0.05), JAK2/STAT3 ratios increased significantly (P<0.01), and Bcl-2/bax ratios decreased significantly (P<0.01); P-STAT3 and IL-6 protein levels were inhibited significantly in higher concentration. CONCLUSIONS: JAK/STAT3 signaling pathway participates in apoptosis of PC-9 cells induced by icotinib. The most likely mechanism is icotinib inhibited the gene expression levels of JAK2, STAT3 and Bcl 2, so with the P-STAT3 and IL-6 protein levels, and mediated gene Bax overexpression. PMID- 27186297 TI - Abate Cytochrome C induced apoptosome to protect donor liver against ischemia reperfusion injury on rat liver transplantation model. AB - OBJECTIVE: Aim of this study is to protect donor liver against ischemia reperfusion injury by abating Cytochrome C induced apoptosome on rat model. METHODS: A total of 25 clean SD inbred male rats were used in this research. The rats in ischemia-reperfusion injury group (I/R group, n=5) were under liver transplantation operation; rats in dichloroacetate diisopropylamine group (DADA group, n=5) were treated DADA before liver transplantation; control group (Ctrl group, n=5); other 10 rats were used to offer donor livers. RESULTS: In DADA therapy group, Cytochrome C expression in donor hepatocellular cytoplasm was detected lower than that in I/R group. And the Cytochrome C induced apoptosome was also decreased in according to the lower expressions of Apaf-1 and Caspase3. Low level of cleaved PARP expression revealed less apoptosis in liver tissue. The morphology of donor liver mitochondria in DADA group was observed to be slightly edema but less than I/R group after operation 12 h. The liver function indexes of ALT and AST in serum were tested, and the results in DADA group showed it is significantly lower than I/R group after operation 12 h. The inflammation indexes of IL-6 and TNF-alpha expressions in DADA group were significantly lower than that in I/R group after operation 24 h. CONCLUSION: The dichloroacetate diisopropylamine treatment could protect the hepatocellular mitochondria in case of the spillage of Cytochrome C induced apoptosome, and protect the liver against ischemia-reperfusion injury. Thus, it may be a method to promote the recovery of donor liver function after transplantation. PMID- 27186298 TI - MicroRNA-183 correlates cancer prognosis, regulates cancer proliferation and bufalin sensitivity in epithelial ovarian caner. AB - Background we intended to explore the functional implication of microRNA-183 (miR 183) in predicting clinical prognosis and regulating cancer proliferation and bufalin sensitivity in epithelial ovarian cancer (EOC). Methods In 75 EOC patients, miR-183 expression was examined, by quantitative RT-PCR (qRT-PCR), between paired EOC tumors and adjacent normal tissues, and between tumor samples from patients at early clinical stages and those at advanced clinical stages. The association of serum miR-183 and patients' clinicopathological variables were examined. The overall survival (OS) was estimated by Kaplan-Meier model. And the possibility of miR-183 as a prognostic biomarker for EOC was examined by cox proportional hazard regression model. In EOC cell lines SKOV3 and ES-2 cells, lentiviral transduction was conducted to genetically suppress miR-183. The effect of miR-183 downregulation on EOC in vitro growth, bufalin sensitivity and in vivo tumorigenicity were examined. Results MiR-183 was highly expressed in EOC tumors, as well ass in patients at advanced clinical stages. Serum miR-183 was significantly associated with major clinicopathological variables in EOC patients, such as clinical stage and lymph node metastases. High level of serum miR-183 was associated with poor OS in EOC patients, and proved to be a potential biomarker for EOC. In EOC cell lines, functional assays demonstrated that miR-183 downregulation inhibited cancer proliferation, enhanced bufalin sensitivity and reduced tumorigenicity in vivo. Conclusion MiR-183 may be a prognostic biomarker for EOC, and inhibiting miR-183 may have therapeutic effect to inhibit tumor growth in EOC. PMID- 27186299 TI - Overexpression of GOLPH3 is associated with poor survival in Non-small-cell lung cancer. AB - As a highly conserved protein of the Golgi apparatus, Golgi phosphoprotein 3 (GOLPH3) has been shown to be involved in tumorigenesis. This study aims to explore the expression and significance of GOLPH3 in non-small-cell lung cancer (NSCLC). We found that GOLPH3 expression was significantly elevated in NSCLC tissues when compared with adjacent lung tissues (p<0.01). Moreover, GOLPH3 expression was significantly associated with histological type (p<0.01), differentiation (p<0.01), and lymph node metastasis (p<0.05). Kaplan-Meier survival analysis showed that overall survival of patients with high expression of GOLPH3 was significantly shorter (n=100, p<0.05). In addition, GOLPH3 knock down in two independent NSCLC cell lines inhibited cell viability through the induction of cell cycle arrest and apoptosis. In conclusion, GOLPH3 is closely related to the progression in NSCLC and could be served as a potential prognostic biomarker and therapeutic target for NSCLC. PMID- 27186300 TI - The mechanism of acetylcholine receptor in binding MuSK in myasthenia gravis and the role of HSP90 molecular chaperone. AB - As an autoimmune disease, myasthenia gravis is caused by the dysfunction of neural transmission. Acetylcholine is known to exert its function after entering into synaptic cleft through binding onto postsynaptic membrane. The role of acetylcholine in binding MuSK in myasthenia gravis, however, remains unknown. A total of 38 myasthenia gravis patients and 27 healthy controls were included in this study for the detection of the expression of MuSK using immunofluorescent method. Expression of both MuSK and interleukin-6 (IL-6) were measured by Western blot, followed by the correlation analysis between heat shock protein 90 (HSP90) and IL-6 which were measured by enzyme-linked immunosorbent assay (ELISA). In myasthenia gravis patients, MuSK was co-localized with acetylcholine at the postsynaptic membrane. Such accumulation of MuSK, however, did not occur in normal people. Meanwhile we also observed elevated expression of IL-6 in myasthenia gravis patients (p<0.05). ELISA assay showed higher expression of HSP90 in patients. Further signaling pathway screening revealed the activation of IL-6-mediated pathways including STAT3 and SPH2. In conclusion, MuSK was co localized with acetylcholine in myasthenia gravis patients, with elevated expression. HSP90 in disease people can activate IL-6 mediated signaling pathways. PMID- 27186301 TI - Cardiomyocyte specific deletion of PP2A causes cardiac hypertrophy. AB - Cardiac hypertrophy is a common pathological alteration in heart disease, which has been reported to be connected with serine/threonine protein phosphatases that control the dephosphorylation of a variety of cardiac proteins. Herein, we generated protein phosphatase type 2A knockout expressing a tamoxifen-inducible Cre recombinase protein fused to two mutant estrogen-receptor ligand-binding domains (MerCreMer) under the control of the a-myosin heavy chain promoter. Cardiac function of mice was determined by echocardiography. Decrease in PP2A activity leads to increased cardiomyocyte hypertrophy and fibrosis. Loss of PP2ACalpha leads to the heart failure, including the changes of EF, FS, LV, ANP and BNP. On the molecular level, knockout mice shows increased expression of B55a and B56e at 60 days after tamoxifen injection. Additionally, the regulation of the Akt/GSK3beta/beta-catenin pathway is severely disturbed in knockout mice. In conclusion, cardiomyocyte specific deletion of PP2A gene causes the cardiac hypertrophy. We will use the knockout mice to generate a type of cardiomyocyte hypertrophy mouse model with myocardial fibrosis. PMID- 27186302 TI - miR-141 modulates osteoblastic cell proliferation by regulating the target gene of lncRNA H19 and lncRNA H19-derived miR-675. AB - Increasing evidence has reported the significant roles of lncRNA or miRNAs in the biology of various diseases. This study was aimed to elucidate the potential roles of miR-141 and lncRNA H19 and H19-derived miR-675 in regulating osteoblasts proliferation and apoptosis and to explore its potential mechanism. miR-141 mimic or miR-141 inhibitor or siRNA-H19 or miR-675 inhibitor was transfected into human hFOB1.19 cells. The effects or miR-141 expression on H19 or miR-675 expression, on osteoblasts proliferation and apoptosis were analyzed. Moreover, effects of H19 and miR-675 expression on cell proliferation were also analyzed. The results showed that miR-141 was down-regulated in both hFOB1.19 cells and osteosarcoma tissues. The overexpressed miR-141 suppressed H19 and miR-675 expression in hFOB1.19 cells. Besides, miR-141 suppression significantly increased cell viability but this effect was blocked by silencing H19 or miR-675 inhibitor, which is similar to the effects on VEGF and IGF2 expression. Furthermore, miR-141 overexpression induced osteoblasts apoptosis, but decreased the levels of caspase 3 and the Bcl-2/Bax ratio. Taken together, our study revealed that tumor suppressor miR-141 overexpression suppressed osteoblasts proliferation but induced apoptosis through down-regulating H19 or miR-675 in osteosarcoma. This study may provide theoretical basis for illustrating the interaction between lncRNA and miRNAs in osteosarcoma and for the therapeutic target of miR-141 in osteosarcoma treatment. PMID- 27186303 TI - IER5 promotes irradiation- and cisplatin-induced apoptosis in human hepatocellular carcinoma cells. AB - PURPOSE: To elucidate the mechanisms of the immediate-early response gene 5 (IER5) effect on the apoptosis induced by irradiation and cisplatin (CDDP) in human hepatocellular carcinoma (HepG2) cells. METHODS: We generated IER5 overexpression stable cells (HepG2/IER5) using Lipofectamine 2000 transfection HepG2 cells. Cell apoptosis was induced by irradiation and cisplatin treatments, and cell proliferation (viability) and apoptosis were evaluated by MTT and flow cytometry assays. Protein expression was determined by Western blot. RESULTS: The growth of the IER5 overexpression cells was significantly inhibited after six days of (60)Co gamma-irradiation exposure (p<0.01) compared with the cell growth of vector control cells. Furthermore, the HepG2/IER5 cells were arrested at the G2/M phases. We also found that the expression of phospho-Akt was reduced, and the levels of cleaved caspase-3 and PARP were increased after the treatment of HepG2/IER5 cells with gamma-irradiation and cisplatin. CONCLUSION: Our results suggest that the overexpression of IER5 can inhibit cell growth and enhance the cell apoptosis induced by exposure to radiation or cisplatin. The overexpression of IER5 can be utilized as a targeting strategy to improve the outcomes of radiotherapy used for the treatment of patients with liver cancer. PMID- 27186304 TI - Genome-wide association study identified PLCE1- rs2797992 and EGFR- rs6950826 were associated with TP53 expression in the HBV-related hepatocellular carcinoma of Chinese patients in Guangxi. AB - OBJECTIVE: The genome-wide association approach was employed to explore the association between single nucleotide polymorphisms (SNPs) and TP53 expression in the HBV-related hepatocellular carcinoma (HCC) of Chinese patients in Guangxi. METHODS: 403 HBV-related HCC patients were recruited into this study and classified according to the TP53 expression in the cancer by immunohistochemistry. DNA was extracted from the cancer and genotyped with the Human ExomeBeadChip 12v1-1 system; quality control and principal-component analysis (PCA) were applied for data analysis. RESULTS: The Genome-wide association analysis indicated that rs2797992 with a P value of 4.35 * 10(-5) locus in PLCE1 gene and rs6950826 with a P value of 2.2 * 10(-3) locus in EGFR gene were associated with TP53 expression in the HCC. A allele of rs2797992 predicted a decreased risk for TP53 expression in HCC. In contrast, A allele of rs6950826 increased the risk for TP53 expression. There was no strong LD locus in the tested regions. PLCE1 and EGFR were associated with TP53 in pathway and at HCC mRNA level. CONCLUSION: rs2797992 of PLCE1 gene and rs6950826 of EGFR gene are associated with TP53 expression, but not with the prognosis of HBV-related HCC in HBV-related HCC of Chinese patients in Guangxi. PMID- 27186305 TI - MicroRNA-145 regulates platelet-derived growth factor-induced human aortic vascular smooth muscle cell proliferation and migration by targeting CD40. AB - The objective of this study is to investigate the expression of microRNA (miR) 145 in human aortic vascular smooth muscle cells (VSMCs) and the effect of miR 145 in the biological behavior and expression of CD40 in VSMCs. Cells were treated with either miR-145 or miR-145 inhibitor. Cell proliferation was analyzed by a colony formation assay and a methyl thiazolyl tetrazolium assay. Cell migration and invasion were assessed using a transwell assay, an invasion assay, and a wound healing assay. A luciferase reporter assay was used to detect the interaction between miR-145 and CD40. Expression of alpha-SMA, calponin, osteopontin (OPN), epiregulin, activator protein-1 (AP-1) and CD40 was measured using real-time RT-PCR for mRNA levels and Western blotting for protein levels. Overexpression of miR-145 significantly inhibited VSMC proliferation, invasion and migration. Furthermore, OPN, epiregulin, AP-1 and CD40 expression at the mRNA and protein levels was down-regulated by overexpression of miR-145. However, alpha-SMA and calponin expression at the mRNA and protein levels was up-regulated by overexpression of miR-145. In addition, the luciferase reporter assay showed that CD40 may be a direct target gene of miR-145 in VSMC initiation and development. Moreover, these data demonstrate that the up-regulation of CD40 is critical for miR-145-mediated inhibitory effects on platelet-derived growth factor-induced cell proliferation and migration in human VSMCs. In summary, CD40, a direct target of miR-145, reverses the inhibitory effects of miR-145. These results suggest that the specific modulation of miR-145 in human VSMCs may be an attractive approach for the treatment of proliferative vascular diseases. PMID- 27186306 TI - MicroRNA-544 inhibits glioma proliferation, invasion and migration but induces cell apoptosis by targeting PARK7. AB - Glioma is a common type of primary brain tumor. The survival rate in people with malignant gliomas is extremely low associated with the lack of effective treatment. Here, we firstly observed that miR-544 expression is downregulated in glioma tissues and its overexpression in glioma cell line dramatically reduces cell proliferation, migration and invasion. In addition, we found that the tumor growth in nude mouse was as well inhibited by miR-544 overexpressed in glioma cell. Our further investigation showed that the inhibitor role of miR-544 in tumor development was related to the downregulated expression of Park7 gene which has been demonstrated as a functional downstream target of miR-544. Thus, our discovery suggested that miR-544 might used as a therapeutic reagent for the treatment of glioma in the future. PMID- 27186307 TI - Effects of combined delivery of extremely low frequency electromagnetic field and magnetic Fe3O4 nanoparticles on hepatic cell lines. AB - Magnetic Fe3O4 nanoparticles (MNPs) have shown promise as drug carriers for treating lung and liver tumors in vivo. However, little is known about the combined delivery of these MNPs with a second approach, extremely low frequency electro-magnetic field (ELFF) exposure, which has been shown to have value for in vitro treatment of tumor cells. Here, ELFF and MNPs were combined to treat healthy (HL-7702) and cancerous (Bel-7402, HepG2) hepatic cells lines to explore the potential therapeutic effects, bio-mechanisms, and potential toxicity of a combined drug-free treatment in vitro. Flow cytometry for anti-AFP (alpha fetal protein) antibody, which coated the MNPs, indicated that the combined treatment induced Bel-7402 and HepG2 hepatoma cells lines into early apoptosis, without significant effects on healthy hepatic cells. This effect appeared to be mediated through cellular membrane ion metabolism. The presence of AFP-loaded MNPs strengthened the effects of ELFF on tumor cells, inducing a higher frequency of early apoptosis, while having minimal toxic effects on healthy HL-7702 cells. Western blotting revealed that the apoptosis-triggering BCL proteins were up regulated in hepatoma cells compared to healthy cells. Flow cytometry and patch clamp studies revealed that this resulted from a higher MNP uptake ratio and greater cellular membrane ion exchange current in tumor cells compared to HL-7702 cells. Further, patch-clamp results showed that combining MNPs with ELFF treatment induces cells into early apoptosis through an ion metabolism disturbance in cells, similar to ELFF treatment. In brief, the combination of ELFF and MNPs had beneficial effects on tumor cells without significant toxicity on healthy cells, and these effects were associated with cellular MNP uptake. PMID- 27186308 TI - miRNA-296-3p modulates chemosensitivity of lung cancer cells by targeting CX3CR1. AB - Lung cancer is the most common type of cancer-related death in developed countries. MicroRNAs (miRNAs) are small non-coding RNAs, which regulates gene expression in cancer. Recent studies demonstrate that the microRNA-293-3p (miR 293-3p) may play as an oncogene or a tumor suppressor. However, its expression and roles in non-small cell lung cancer (NSCLC) is not known. In this study, our purpose is to investigate the expression and roles of miR-296-3p in NSCLC. The findings indicated that miR296-3p inhibited NSCLC cell proliferation, enhance the drug resistance, and apoptosis. Data of luciferase reporter assays demonstrated that the CX3CR1 gene was a direct regulator of tumorsuppressive miR296-3p. Moreover, overexpressed CX3CR1 was confirmed in NSCLC clinical specimens. Inhibition of CX3CR1 could inhibit cancer cellular survival and increase chemotherapy sensitivity. There was a negative relationship between miR296-3p and CX3CR1 expression in NSCLC tissues. Our study elucidates that miR296-3p plays a suppressive role in NSCLC by inhibiting CX3CR1 expression. PMID- 27186309 TI - Distribution of pancreatic B cell imaging agent (99m)Tc-DTPA-NGN2 in the body and animal experimental research on pancreatic B cell functional imaging. AB - PURPOSE: To explore the feasibility of the application of (99m)Tc-DTPA Nateglinide as a nuclear medicine imaging agent for evaluating pancreatic B cell function. METHODS: (1) Distribution of the experiment: Forty-two mice were selected and divided into seven groups. Each mice was injected with 3.7 MBq (100 MUCi) of (99m)Tc-DTPA-NGN2 from the vena caudalis and was sacrificed by bloodletting at five minutes, 15 minutes, 30 minutes, one hour, two hours, four hours and six hours, respectively. Then, their tissues and organs such as the heart, liver, spleen, brain, kidneys, bones, small bowels, stomach and pancreas,and blood were collected, weighted, and their radioactivity was tested. Subsequently, the percentage injection dose rate (%ID/g) per gram of tissue was calculated. (2) Imaging experiment: Thirty-five mice were selected and divided into seven groups. Each was injected with 18.5 MBq (100 MUCi) of (99m)Tc-DTPA NGN2 from the vena caudalis and imaging were conducted at the same time as above. (3) Forty-eight Wistar rats were attained and randomly divided into four groups. The first group served as the healthy control group, while the second, third and fourth groups were diabetic model groups induced by intraperitoneally injecting STZ at different doses. Each group was injected with (99m)Tc-DTPA-Nateglinide from the vena caudalis, and radiological evaluations were conducted at 30 minutes, one hour, 1.5 hours and two hours, respectively. The data obtained were estimated using a correlation comparison with the levels of insulin and immunohistochemical count of beta cells. RESULTS: The (99m)Tc-DTPA-Nateglinide demonstrated good imaging in the pancreases of mice and rats, and was positively correlated to the level of insulin and the number of pancreatic beta cells. CONCLUSION: Pancreatic beta cell imaging using (99m)Tc-DTPA-Nateglinide may be a method to evaluate pancreatic beta cell function. PMID- 27186310 TI - Phenylbutyrate prevents disruption of blood-spinal cord barrier by inhibiting endoplasmic reticulum stress after spinal cord injury. AB - This study aims to investigate the role of endocytoplasmic reticulum (ER) stress induced by spinal cord injury (SCI) in blood-spinal cord barrier (BSCB) disruption and the effect of phenylbutyrate (PBA) on BSCB disruption after SCI. After a moderate contusion injury at the T9 level of spinal cord with a vascular clip, PBA was immediately administered into injured rat via intraperitoneal injection (100 mg/kg) and then further treated once a day for 2 weeks for behavior test. Spinal cord was collected at 1 day post-injury for evaluation of the effects of ER stress and PBA on BSCB disruption after SCI. PBA significantly attenuated BSCB permeability and degradation of tight junction molecules such as P120, beta-catenin, Occludin and Claudin5 at 1 day after injury and improved functional recovery in the rat model of trauma. The BSCB protective effect of PBA is related to the inhibition of ER stress induced by SCI. In addition, PBA significantly inhibited the increase of ER stress markers and prevents loss of tight junction and adherens junction proteins in TG-treated human brain microvascular endothelial cells (HBMEC). Taken together, our data demonstrate that therapeutic strategies targeting ER stress may be suitable for the therapy of preserving BSCB integrity after SCI. PBA may be a new candidate as a therapeutic agent for protecting SCI by a compromised BSCB. PMID- 27186311 TI - Radiofrequency ablation for postsurgical thyroid removal of differentiated thyroid carcinoma. AB - Differentiated thyroid carcinoma (DTC) is the most common endocrine malignancy. Surgical removal with radioactive iodine therapy is recommended for recurrent thyroid carcinoma, and the postsurgical thyroid removal is critical. This study evaluated the clinical values of radiofrequency ablation (RFA) in the postsurgical thyroid removal for DTC. 35 DTC patients who had been treated by subtotal thyroidectomy received RFA for postsurgical thyroid removal. Before and two weeks after RFA, the thyroid was examined by ultrasonography and (99m)TcO4 ( ) thyroid imaging, and the serum levels of free triiodothyronine (FT3), free thyroxin (FT4), thyroid stimulating hormone (TSH) and thyroglobulin (Tg) were detected. The efficacy and complications of RFA were evaluated. Results showed that, the postsurgical thyroid removal by RFA was successfully performed in 35 patients, with no significant complication. After RFA, the average largest diameter and volume were significantly decreased in 35 patients (P > 0.05), and no obvious contrast media was observed in ablation area in the majority of patients. After RFA, the serum FT3, FT4 and Tg levels were markedly decreased (P < 0.05), and TSH level was significantly increased (P < 0.05). After RFA, radioiodine concentration in the ablation area was significantly reduced in the majority of patients. The reduction rate of thyroid update was 0.69+/-0.20%. DTC staging and interval between surgery and RFA had negative correlation (Pearson coefficient = -0.543; P = 0.001), with no obvious correlation among others influential factors. RFA is an effective and safe method for postsurgical thyroid removal of DTC. PMID- 27186312 TI - MiR-129-5p-mediated Beclin-1 suppression inhibits endothelial cell autophagy in atherosclerosis. AB - Endothelial cell injury and subsequent death play an essential role in the pathogenesis of atherosclerosis. Autophagy of endothelial cells antagonizes the development of atherosclerosis, whereas the underlying molecular mechanisms are unclear. MicroRNA-129-5p (miR-129-5p) is a well-defined tumor suppressorin some types of cancer, while it is unknown whether miR-129-5p may also play a role in the development of atherosclerosis. Here, we addressed this question in the current study. We examined the levels of endothelial cell autophagy in ApoE (-/-) mice suppled with high-fat diet (HFD), a mouse model for atherosclerosis (simplified as HFD mice). We analyzed the levels of Beclin-1 and the levels of miR-129-5p in the purified CD31+ endothelial cells from mouse aorta. Prediction of the binding between miR-129-5p and 3'-UTR of Beclin-1 mRNA was performed by bioinformatics analyses and confirmed by a dual luciferase reporter assay. The effects of miR-129-5p were further analyzed in an in vitro model using oxidized low-density lipoprotein (ox-LDL)-treated human aortic endothelial cells (HAECs). We found that HFD mice developed atherosclerosisin 12 weeks, while the control ApoE (-/-) mice that had received normal diet (simplified as CTL mice) did not. Compared to CTL mice, HFD mice had significantly lower levels of endothelial cell autophagy, resulting from decreases in Beclin-1 protein, but not mRNA. The decreases in Beclin-1 in endothelial cells were due to HFD-induced increases inmiR-129-5p, which suppressed the translation of Beclin-1 mRNA via 3'-UTR binding. These in vivo findings were reproduced in vitro on ox-LDL-treated HAECs. Together, these data suggest that upregulation of miR-129-5p by HFD may impair the protective effects of endothelial cell autophagy against development of atherosclerosis through suppressing protein translation of Beclin-1. PMID- 27186314 TI - Sestrin2 expression is a favorable prognostic factor in patients with non-small cell lung cancer. AB - The purpose of this study was to evaluate the prognostic value of Sestirn2 in patients with non-small cell lung cancer (NSCLC). Quantitative real-time ( RT PCR) and western blot were performed to investigate the mRNA and protein expression of Sestirn2 in NSCLC and corresponding non-cancerous tissues. Immunohistochemistry was used to detect the expression of Sestirn2 in 210 NSCLC tissue samples. Overall survival was calculated by the Kaplan-Meier method and analyzed by the log-rank test between different groups. The results indicated that the Sestirn2 expression was significantly lower in NSCLC tissues than the corresponding non-cancerous lung tissues. Low Sestirn2 expression was related to poor tumor differentiation, advanced TNM stage, and lymph node metastasis. Patients with high Sestirn2 expression had longer overall survival than those with low expression levels, which was consistent with the results of the subgroup analysis. Multivariate analysis showed that high Sestirn2 expression was a favorable prognostic factor for NSCLC patients. Our study indicated that Sestirn2 could play an important role in the observation of prognosis in NSCLC and might be a valuable marker for predicting the treatment outcome in patients with NSCLC. PMID- 27186313 TI - microRNA-22 attenuates neuronal cell apoptosis in a cell model of traumatic brain injury. AB - Traumatic brain injury (TBI) is a major cause of injury-related deaths, and the mechanism of TBI has become a research focus, but little is known about the mechanism of microRNAs in TBI. The aim of this study is the role of microRNA-22 (miR-22) in TBI-induced neuronal cell apoptosis. Rat cortical neurons were cultured and the TBI model was induced by scratch injury in vitro, before which miR-22 level was altered by transfection of agomir or antagomir. Lactate dehydrogenase (LDH) release and TUNEL assays were performed to examine neuronal cell injury and apoptosis. The activity of caspase 3 (CASP3) and level changes of several apoptosis factors including B-cell lymphoma 2 (BCL2), BCL2-associated X protein (BAX), phosphatase and tensin homolog (PTEN) and v-AKT murine thymoma viral oncogene homolog 1 (AKT1) were detected. Results showed that TBI model cells possessed a downregulated miR-22 level (P < 0.001) and more LDH release and apoptotic cells indicating the aggravated neuronal cell injury and apoptosis induced by TBI. miR-22 agomir attenuated neuronal cell injury and apoptosis of the TBI model. It also caused the corresponding changes in CASP3 activity and other apoptosis factors, with cleaved CASP3, BAX and PTEN inhibited and BCL2 and phosphorylated AKT1 promoted, while miR-22 antagomir had the opposite effects. So miR-22 has neuroprotective roles of attenuating neuronal cell injury and apoptosis induced by TBI, which may be associated with its regulation on apoptosis factors. This study reveals miR-22 as a potential approach to TBI treatment and detailed mechanism remains to be uncovered. PMID- 27186316 TI - miR-128 modulates hepatocellular carcinoma by inhibition of ITGA2 and ITGA5 expression [Retraction]. AB - [This retracts the article on p. 1564 in vol. 7, PMID: 26550456.]. PMID- 27186315 TI - Icariin exerts estrogen-like activity in ameliorating EAE via mediating estrogen receptor beta, modulating HPA function and glucocorticoid receptor expression. AB - BACKGROUND: Estrogen exerts neuroprotective and anti-inflammatory effects in EAE and multiple sclerosis (MS), but its clinical application is hindered due to side effects and risk of tumor. Phytoestrogen structurally or functionally mimics estrogen with fewer side effects than endogenous estrogen. Icariin (ICA), an active component of Epimedium extracts, demonstrates estrogen-like neuroprotective effects. However, it is unclear whether ICA is effective in EAE and what are the underlying mechanisms. OBJECTIVE: To determine the therapeutic effects of ICA in EAE and explore the possible mechanisms. METHODS: C57BL/6 EAE mice were treated with Diethylstilbestrol, different dose of ICA and mid-dose ICA combined with ICI 182780. The clinical scores and serum Interleukin-17 (IL-17), Corticosterone (CORT) concentrations were then analyzed. Western blot were performed to investigate the expressions of glucocorticoid receptor (GR), estrogen receptor alpha (ERalpha) and ERbeta in the cerebral white matter of EAE mice. RESULTS: High dose ICA is equally effective in ameliorating neurological signs of EAE as estrogen. Estrogen and ICA has no effects on serum concentrations of IL-17 in EAE. While the CORT levels were decreased by ICA at mid or high doses, the expressions of GR, ERalpha and ERbeta were up-regulated by estrogen or different doses of ICA in a dosedependent manner. Estrogen induced the elevation of ERalpha more markedly than ICA. In contrast, ICA at mid and high doses promoted ERbeta more significantly than estrogen. CONCLUSION: ICA exerts estrogen like activity in ameliorating EAE via mediating ERbeta, modulating HPA function and up-regulating the expression of GR in cerebral white matter. ICA may be a promising therapeutic option for MS. PMID- 27186317 TI - Optogenetics for neurodegenerative diseases. AB - Neurodegenerative diseases are devastating conditions that lead to progressive degeneration of neurons. Neurodegeneration may result in ataxia, dementia, and muscle atrophies, etc. Despite enormous research efforts that have been made, there is lack of effective therapeutic interventions for most of these diseases. Optogenetics is a recently developed novel technique that combines optics and genetics to modulate the activity of specific neurons. Optogenetics has been implemented in various studies including neuropsychiatric disorders and neurodegenerative diseases. This review focuses on the recent advance in using this technique for the studies of common neurodegenerative diseases. PMID- 27186318 TI - Neuroprotective effect of lidocaine: is there clinical potential? AB - Local anesthetic lidocaine has been shown to be protective in animal models of focal and global ischemia as well as in in vitro hypoxic models. Lidocaine has been tested in patients for its potential protective effect on postoperative cognitive dysfunction. This mini-review summarizes the laboratory and clinical evidences and discusses its clinical applications as neuroprotective agent. PMID- 27186320 TI - Role of autophagy in megakaryocyte differentiation and platelet formation. AB - Autophagy is a conserved biological process for digestion and recycling of cytoplasmic constituents in eukaryotic cells. Autophagy may trigger cell death or promote cell survival following various forms of stress. The emerging roles of autophagy in megakaryopoiesis, thrombopoiesis, and platelet function have been uncovered using not only in vitro and in vivo genetic models, but also in clinical observations of autophagic structure in patients with thrombocytopenic disorders. Inhibition of autophagy in early stage of megakaryocyte differentiation appears to impede megakaryocyte maturation, reduce platelet formation, and affect platelet function, whereas autophagic deficiency in mature megakaryocytes gives rise to abnormal platelet activation and function without changing platelet size and number. On the other hand, induction of autophagy by rapamycin in megakaryocytes exhibited substantial therapeutic benefits in patients with immune thrombocytopenic purpura (ITP). This mini-review is to highlight recent progresses in understanding the regulation of autophagy in megakaryopoiesis, thrombopoiesis and platelet function to bridge the gap between autophagy and megakaryocyte/platelet pathophysiology. PMID- 27186321 TI - Intracellular zinc distribution in mitochondria, ER and the Golgi apparatus. AB - Zinc (Zn(2+)) is required for numerous cellular functions. As such, the homeostasis and distribution of intracellular zinc can influence cellular metabolism and signaling. However, the exact distribution of free zinc within live cells remains elusive. Previously we showed the release of zinc from thapsigargin/IP3-sensitive endoplasmic reticulum (ER) storage in cortical neurons. In the present study, we investigated if other cellular organelles also contain free chelatable zinc and function as organelle storage for zinc. To identify free zinc within the organelles, live cells were co-stained with Zinpyr 1, a zinc fluorescent dye, and organelle-specific fluorescent dyes (MitoFluor Red 589: mitochondria; ER Tracker Red: endoplasmic reticulum; BODIPY TR ceramide: Golgi apparatus; Syto Red 64: nucleus). We examined organelles that represent potential storing sites for intracellular zinc. We showed that zinc fluorescence staining was co-localized with MitoFluor Red 589, ER Tracker Red, and BODIPY TR ceramide respectively, suggesting the presence of free zinc in mitochondria, endoplasmic reticulum, and the Golgi apparatus. On the other hand, cytosol and nucleus had nearly no detectable zinc fluorescence. It is known that nucleus contains high amount of zinc binding proteins that have high zinc binding affinity. The absence of zinc fluorescence suggests that there is little free zinc in these two regions. It also indicates that the zinc fluorescence detected in mitochondria, ER and Golgi apparatus represents free chelatable zinc. Taken together, our results support that these organelles are potential zinc storing organelles during cellular zinc homeostasis. PMID- 27186319 TI - The mitochondria-targeted antioxidant MitoQ attenuates liver fibrosis in mice. AB - Oxidative stress plays an essential role in liver fibrosis. This study investigated whether MitoQ, an orally active mitochondrial antioxidant, decreases liver fibrosis. Mice were injected with corn oil or carbon tetrachloride (CCl4, 1:3 dilution in corn oil; 1 ul/g, ip) once every 3 days for up to 6 weeks. 4 Hydroxynonenal adducts increased markedly after CCl4 treatment, indicating oxidative stress. MitoQ attenuated oxidative stress after CCl4. Collagen 1alpha1 mRNA and hydroxyproline increased markedly after CCl4 treatment, indicating increased collagen formation and deposition. CCl4 caused overt pericentral fibrosis as revealed by both the sirius red staining and second harmonic generation microscopy. MitoQ blunted fibrosis after CCl4. Profibrotic transforming growth factor-beta1 (TGF-beta1) mRNA and expression of smooth muscle alpha-actin, an indicator of hepatic stellate cell (HSC) activation, increased markedly after CCl4 treatment. Smad 2/3, the major mediator of TGF-beta fibrogenic effects, was also activated after CCl4 treatment. MitoQ blunted HSC activation, TGF-beta expression, and Smad2/3 activation after CCl4 treatment. MitoQ also decreased necrosis, apoptosis and inflammation after CCl4 treatment. In cultured HSCs, MitoQ decreased oxidative stress, inhibited HSC activation, TGF beta1 expression, Smad2/3 activation, and extracellular signal-regulated protein kinase activation. Taken together, these data indicate that mitochondrial reactive oxygen species play an important role in liver fibrosis and that mitochondria-targeted antioxidants are promising potential therapies for prevention and treatment of liver fibrosis. PMID- 27186322 TI - Zinc wave during the treatment of hypoxia is required for initial reactive oxygen species activation in mitochondria. AB - Mitochondrial reactive oxygen species (ROS) are known to accumulate during chemical hypoxia, causing adverse effects on cell function and survival. Recent studies show important role zinc accumulation plays in dysfunction associated with hypoxia. It is well known that ROS accumulation also plays a major role in cellular damage by hypoxia. In this study, fluorescent imaging and pharmacological methods were used in live HeLa cells to determine role of zinc in initial ROS accumulation in mitochondria during chemical hypoxia (oxygen glucose depravation with 4 mM sodium dithionite). Accumulation of both was observed as a very rapid phenomenon with initial rapid zinc increase (zinc wave) within 60 seconds of hypoxia onset and ROS increase within 4.5 minutes. Zinc chelation with TPEN removed the initial zinc wave which in turn abolished ROS accumulation. Influx of exogenous zinc induced rapid ROS accumulation. Inhibition of NADPH oxidase with apocynin, a NADPH oxidase inhibitor, showed significant and prolonged reduction in zinc induced ROS accumulation. We proposed a novel mechanism of intracellular zinc increase that activates NADPH oxidase which in turn triggers mitochondrial ROS production. PMID- 27186323 TI - DNA methylation and genetic polymorphisms of the Leptin gene interact to influence lung function outcomes and asthma at 18 years of age. AB - The leptin gene (LEP) plays a regulatory role in satiety, inflammation, and allergy. Prior findings linking leptin to asthma motivated us to investigate whether DNA methylation (DNA-M) of CpG (cytosine-phosphate-guanine) sites in concert with single nucleotide polymorphisms (SNPs) of LEP can explain the risk of asthma and lung function. Methylation of CpG sites was assessed using the Illumina Infinium Human Methylation 450 beadchip in blood samples collected from 10- and 18-year-old boys and girls from the Isle of Wight (IOW) birth cohort (UK). Four LEP SNPs were genotyped. Linear and log linear models were used for the analysis, adjusting for false discovery rate (FDR). The analyses were repeated in the BAMSE cohort (Sweden). In the IOW study, the interaction of cg00666422 and rs11763517 (CT vs TT and CC) was associated with FEV1 (FDR adjusted p-value: 0.03), FEV1/FVC ratio (FDR-adjusted p-value: 0.0096), and FEF25 75% (FDR-adjusted p-value: 0.00048) such that they decreased with increasing DNA M. The interaction of the same CpG-SNP pair was also associated with increased risk of asthma at age 18. We replicated the findings for FEV1/FVC and FEF25-75% in a smaller sample of 34 participants at age 10. Regarding the BAMSE cohort, although, the interaction of cg00666422 and rs11763517 on lung function were not significant, the direction of the effect was the same as in IOW cohort. Thus, penetrance of LEP genotype seems to be modified by methylation at cg00666422 and is linked to airway obstruction and asthma. PMID- 27186324 TI - Telomere length measurement by a novel Luminex-based assay: a blinded comparison to Southern blot. AB - Telomere length (TL) is a potential biomarker of aging and age-related disease risk. We recently published a novel Luminex-based method for high-throughput, low cost TL measurement. Here we describe a blinded comparison of the Luminex method to Southern blot, the most precise TL measurement method. Luminex and Southern blot measurements for the same 50 DNA samples were taken in two independent laboratories; each sample was measured twice, several months apart. The inter assay CV for Luminex ranged from 5.5 to 9.1 (depending on CV estimation method), and Southern blot CV from 1.0 to 1.7. Both measures were inversely associated with age. The correlation between the repeated measurements was 0.66 for Luminex and 0.97 for Southern blot. The correlation between Southern blot and Luminex was 0.65 in round 1 and 0.75 in round 2, and the relationship showed no evidence of non-linearity. Our results demonstrate that the Luminex assay is a valid and reproducible method for high-throughput TL measurement. The Luminex assay involves no DNA amplification, which may make Luminex an attractive alternative to PCR-based TL measurement. PMID- 27186325 TI - GNAS gene mutation may be present only transiently during colorectal tumorigenesis. AB - Mutations of the gene GNAS have been shown to activate the adenylate cyclase gene and lead to constitutive cAMP signaling. Several preliminary reports have suggested a role for GNAS gene mutations during colorectal carcinogenesis, particularly mucinous carcinomas. The aim of this study was to clarify the incidence of GNAS mutations in adenomas (tubular, tubulovillous, and villous), carcinomas with residual adenoma, and carcinomas, and to relate these findings to mutations of the KRAS gene and to the mucinous status of the tumors. We used standard PCR techniques and direct gene sequencing to evaluate tumors for gene mutations. No GNAS mutations were identified in 25 tubular adenomas, but were present in 6.4% of tubulovillous adenomas and 11.2% of villous adenomas. A GNAS mutation was found in 9.7% of the benign portion of carcinoma with residual adenoma, but in none of 86 carcinomas. A similar trend was seen for KRAS mutation across the five groups of tumors. GNAS mutations may function as an important driver mutation during certain phases of colorectal carcinogenesis, but may then be lost once the biological advantage gained by the mutated gene is no longer necessary to sustain or advance tumor development. PMID- 27186326 TI - Placental genetic variations in circadian clock-related genes increase the risk of placental abruption. AB - The genetic architecture of placental abruption (PA) remains poorly understood. We examined variations in SNPs of circadian clock-related genes in placenta with PA risk. We also explored placental and maternal genomic contributions to PA risk. Placental genomic DNA samples were isolated from 280 PA cases and 244 controls. Genotyping was performed using the Illumina Cardio-MetaboChip. We examined 116 SNPs in 13 genes known to moderate circadian rhythms. Logistic regression models were fit to estimate odds ratios (ORs). The combined effect of multiple SNPs on PA risk was estimated using a weighted genetic risk score. We examined independent and joint associations of wGRS derived from placental and maternal genomes with PA. Seven SNPs in five genes (ARNTL2, CRY2, DEC1, PER3 and RORA), in the placental genome, were associated with PA risk. Each copy of the minor allele (G) of a SNP in the RORA gene (rs2899663) was associated with a 30% reduced odds of PA (95% CI 0.52-0.95). The odds of PA increased with increasing placental-wGRS (Ptrend<0.001). The ORs were 1.00, 2.16, 3.24 and 4.48 across quartiles. Associations persisted after the maternal-wGRS was included in the model. There was evidence of an additive contribution of placental and maternal genetic contributions to PA risk. Participants with placental- and maternal-wGRS in the highest quartile, compared with those in the lowest quartile, had a 15.57 fold (95% CI 3.34-72.60) increased odds of PA. Placental variants in circadian clock-related genes are associated with PA risk; and the association persists after control of genetic variants in the maternal genome. PMID- 27186327 TI - Association analysis of a chemo-response signature identified within The Cancer Genome Atlas aimed at predicting genetic risk for chemo-response in ovarian cancer. AB - BACKGROUND: A gene signature associated with chemo-response in ovarian cancer was created through integration of biological data in The Cancer Genome Atlas (TCGA) and validated in five independent microarray experiments. Our study aimed to determine if single nucleotide polymorphisms (SNPs) within the 422-gene signature were associated with a genetic predisposition to platinum-based chemotherapy response in serous ovarian cancer. METHODS: An association analysis between SNPs within the 422-gene signature and chemo-response in serous ovarian cancer was performed under the log-additive genetic model using the 'SNPassoc' package within the R environment (p<0.0001). Subsequent validation of statistically significant SNPs was done in the Ovarian Cancer Association Consortium (OCAC) database. RESULTS: 19 SNPs were found to be associated with chemo-response with statistical significance. None of the SNPs found significant in TCGA were validated within OCAC for the outcome of interest, chemo-response. CONCLUSIONS: SNPs associated with chemo-response in ovarian cancer within TGCA database were not validated in a larger database of patients and controls from OCAC. New strategies integrating somatic and germline information may help to characterize genetic predictors for treatment response in ovarian cancer. PMID- 27186328 TI - Genes, environment and gene expression in colon tissue: a pathway approach to determining functionality. AB - Genetic and environmental factors have been shown to work together to alter cancer risk. In this study we evaluate previously identified gene and lifestyle interactions in a candidate pathway that were associated with colon cancer risk to see if these interactions altered gene expression. We analyzed non-tumor RNA seq data from 144 colon cancer patients who had genotype, recent cigarette smoking, diet, body mass index (BMI), and recent aspirin/non-steroidal anti inflammatory use data. Using a false discovery rate of 0.1, we evaluated differential gene expression between high and low levels of lifestyle exposure and genotypes using DESeq2. Thirteen pathway genes and 17 SNPs within those genes were associated with altered expression of other genes in the pathway. BMI, NSAIDs use and dietary components of the oxidative balance score (OBS) also were associated with altered gene expression. SNPs previously identified as interacting with these lifestyle factors, altered expression of pathway genes. NSAIDs interacted with 10 genes (15 SNPs) within those genes to alter expression of 28 pathway genes; recent cigarette smoking interacted with seven genes (nine SNPs) to alter expression of 27 genes. BMI interacted with FLT1, KDR, SEPN1, TERT, TXNRD2, and VEGFA to alter expression of eight genes. Three genes (five SNPs) interacted with OBS to alter expression of 12 genes. These data provide support for previously identified lifestyle and gene interactions associated with colon cancer in that they altered expression of key pathway genes. The need to consider lifestyle factors in conjunction with genetic factors is illustrated. PMID- 27186329 TI - Genetic polymorphism at codon 546 of the human RAD17 contributes to the risk for esophageal squamous cell carcinoma. AB - Human RAD17, a human homolog of the Schizosaccharomyces pombe cell cycle checkpoint gene RAD17, plays a significant role in activating checkpoint signals in response to DNA damage. We evaluated the association of hRAD17 Leu546Arg (rs1045051), a missense single nucleotide polymorphism, with the risk of esophageal squamous cell carcinoma in relation to smoking and alcohol consumption history in 154 esophageal squamous cell carcinoma male patients and 695 cancer free male controls by a case-control study conducted in Japan. The results showed that the hRAD17 Arg/Arg genotype compared to the Leu/Leu and Leu/Arg genotypes was significantly associated with the risk of the esophageal squamous cell carcinoma with an adjusted odds ratios of 2.22 (95% CI: 1.19-4.16 P=0.013). In stratified studies, the risk of esophageal squamous cell carcinoma was markedly higher in light drinkers (less than 23 g ethanol/day) with the Arg/Arg genotype than in heavy drinkers (excess of 23 g ethanol/day) with the Arg/Arg genotype (OR=2.83, 95% CI: 1.05-7.61, P=0.04). We concluded that the genetic variant of hRAD17 Leu546Arg polymorphism exerts a significant effect on esophageal squamous cell carcinoma risk among Japanese men. PMID- 27186330 TI - Dyslipidemia, insulin resistance and dietary fat intake in obese and normal weight adolescents: the role of uncoupling protein 2 -866G/A gene polymorphism. AB - Obesity in adolescents has been associated with increased cardiovascular risk factors such as dyslipidemia and insulin resistance. Several factors have been proposed to be associated with cardiovascular risk factors in adolescents including dietary habit, physical activity and genetic. This study was aimed to evaluate the interaction between genetic variation and dietary intake on cardiovascular metabolic risk factors in obese and normal weight adolescents. The UCP2 gene was chosen because it was previously correlated with dietary intake and cardiovascular risk factors. This study is a case control study done in 10 senior high school in Yogyakarta. Subjects were obese and normal weight adolescents taken from an obesity screening with age ranged between 16 and 18 years old. Dyslipidemia was observed by measuring total cholesterol, triglyceride, LDL dan HDL level while insulin resistance was determined by calculating fasting glucose and insulin level. Lipid profile, glucose and insulin level were measured after 8 hours of fasting. UCP2 -866G/A gene polymorphism were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results show that obese adolescents had significantly higher blood pressure, total cholesterol, LDL, triglyceride, insulin level and lower HDL level than their normal weight counterparts (all p<0.001). In obese adolescents, UCP2 -866G/A was associated with blood pressure (p=0.025), total cholesterol level (p=0.025), LDL (p=0.024) level and HOMA IR (p<0.001) but not with dietary fat intake (p=0.386). Additionally, subjects with UCP2 -866G/A gene polymorphism and high dietary fat intake had lower risk on obesity compared to those without UCP2 -866G/A gene polymorphism and low dietary fat intake. We conclude that the UCP2 -866G/A was associated with dyslipidemia, insulin resistance in obese adolescents. Additionally, we also observed the interaction between UCP2 -866G/A gene polymorphism and dietary intake on the risk of obesity. PMID- 27186331 TI - Prevalence of common vitamin D receptor gene polymorphisms in HIV-infected and uninfected South Africans. AB - BACKGROUND: Host genetic factors may a play role in susceptibility to infection. Vitamin-D is an immunomodulator that may play a role in HIV infection. Vitamin-D action is mediated by the vitamin-D receptor. We establish prevalence of ApaI, BsmI, FokI and TaqI polymorphisms (VDRPs) amongst a black southern African HIV+ve population and investigate polymorphic differences between HIV+ve and -ve people. METHODS: Seventy-nine sex and age-group matched HIV+ve patients of African origin initiating antiretroviral therapy (ART) and 79 HIV-ve participants, also of African origin, were recruited from a public sector HIV testing and treatment clinic and investigated for the 4 polymorphisms. The genotype frequencies were compared, odds ratios and 95% confidence intervals of the association of HIV status and each genotype were calculated. Both dominant, co-dominant, recessive and allele models were tested. RESULTS: We found no evidence of difference in distribution and association between HIV infection and the genotypes of the BsmI, FokI and TaqI VDR polymorphisms. The genotype distributions were consistent with Hardy-Weinberg equilibrium for these genotypes. The ApaI genotype showed differences in distribution by HIV status in the dominant and co-dominant models. However this finding is cautiously stated as the ApaI genotype violated the Hardy Weinberg equilibrium and frequency of the minor variant was unexpectedly low in this population. CONCLUSION: We do not show convincing differences in distribution of the VDR genotypes among HIV+ve and HIV-ve black southern African persons. Future studies need to be replicated in larger study populations as understanding polymorphic differences and similarities may offer insights into the different susceptibility and progression of HIV in southern African populations. PMID- 27186332 TI - Soluble vascular endothelial growth factor receptors 2 (sVEGFR-2) and 3 (sVEGFR 3) and breast cancer risk in the Swedish Mammography Cohort. AB - Vascular endothelial growth factor (VEGF) is a signalling protein that has been established as a contributor to tumor angiogenesis, and expression of VEGF and its soluble receptors (sVEGFR2 and sVEGFR3) have been demonstrated in breast cancer cells. However, no prospective studies have examined the association between prediagnostic sVEGFR levels and breast cancer risk. We conducted a prospective case-control study nested within the Swedish Mammography Cohort examining the association between sVEGFR2 and 3 levels and breast cancer risk. The analysis included 69 incident breast cancer cases diagnosed after blood collection and 719 controls. Logistic regression models were used to calculate odds ratios and 95% confidence intervals. After adjustment for breast cancer risk factors, sVEGFR2 levels were associated with breast cancer risk (OR=1.28; 95% CI=1.06-1.56 per 1000 ng/L increase in concentration) while sVEGFR3 levels were not related to such risk (OR=1.00; 95% CI=0.93-1.07). Our results suggest that sVEGFR2 levels may be positively associated with breast cancer risk, however future studies with larger case groups are necessary to confirm this association. PMID- 27186334 TI - Karyotype and genome size in Euterpe Mart. (Arecaceae) species. AB - Euterpe (Martius, 1823), a genus from Central and South America, has species with high economic importance in Brazil, because of their palm heart and fruits, known as acai berries. Breeding programs have been conducted to increase yield and establish cultivation systems to replace the extraction of wild material. These programs need basic information about the genome of these species to better explore the available genetic variability. The aim of this study was to compare Euterpe edulis (Martius, 1824), Euterpe oleracea (Martius, 1824) and Euterpe precatoria (Martius, 1842), with regard to karyotype, type of interphase nucleus and nuclear DNA amount. Metaphase chromosomes and interphase nuclei from root tip meristematic cells were obtained by the squashing technique and solid stained for microscope analysis. The DNA amount was estimated by flow cytometry. There were previous reports on the chromosome number of Euterpe edulis and Euterpe oleracea, but chromosome morphology of these two species and the whole karyotype of Euterpe precatoria are reported for the first time. The species have 2n=36, a number considered as a pleisomorphic feature in Arecoideae since the modern species, according to floral morphology, have the lowest chromosome number (2n=28 and 2n=30). The three Euterpe species also have the same type of interphase nuclei, classified as semi-reticulate. The species differed on karyotypic formulas, on localization of secondary constriction and genome size. The data suggest that the main forces driving Euterpe karyotype evolution were structural rearrangements, such as inversions and translocations that alter chromosome morphology, and either deletion or amplification that led to changes in chromosome size. PMID- 27186333 TI - Screening and chromosome localization of two cotton BAC clones. AB - Two bacterial artificial chromosome (BAC) clones (350B21 and 299N22) of Pima 90 53 cotton [Gossypium barbadense Linnaeus, 1753 (2n=4x=52)] were screened from a BAC library using SSR markers. Strong hybridization signals were detected at terminal regions of all A genome (sub-genome) chromosomes, but were almost absent in D genome (sub-genome) chromosomes with BAC clone 350B21 as the probe. The results indicate that specific sequences, which only exist at the terminal parts of A genome (sub-genome) chromosomes with a huge repeat number, may be contained in BAC clone 350B21. When utilizing FISH with the BAC clone 299N22 as probe, a pair of obvious signals was detected on chromosome 13 of D genome (sub-genome), while strong dispersed signals were detected on all A genome (sub-genome) chromosomes. The results showed that peculiar repetitive sequence, which was distributed throughout all A genome (sub-genome) chromosomes, may exist in BAC clone 299N22. The absence of the repetitive sequences, which exist in the two BAC clones, in D genome may account for the genome-size variation between A and D genomes. In addition, the microcolinearity analysis of the clone 299N22 and its homologous region on Gossypium raimondii Ulbrich, 1932 chromosome 13 (D513) indicated that the clone 299N22 might come from A sub-genome of sea island cotton (Gossypium barbadense), and a huge number of small deletions, illegitimate recombination, translocation and rearrangements may have occurred during the genus evolution. The two BAC clones studied here can be used as cytological markers but will be also be helpful to research in cotton genome evolution and comparative genomics. PMID- 27186335 TI - A chromosomal analysis of three species of Timarcha (Coleoptera, Chrysomelidae, Chrysomelinae). AB - The karyotypes of three species of Timarcha Latreille, 1829 have been analysed. Timarcha (Metallotimarcha) metallica (Laicharting, 1781), has 18 + Xyp male meioformula and 2n = 38 chromosomes, similar to those found in the two species of subgenus Americanotimarcha Jolivet, 1948, in agreement with morphological and molecular phylogenetic grounds. Timarcha (Timarcha) carmelenae Petitpierre, 2013 displays 9 + Xyp and 2n = 20 chromosomes as in morphologically related Andalusian species, whereas Timarcha (Timarcha) parvicollis ssp. seidlitzi Kraatz, 1879 shows 11 + Xyp and 2n = 24 chromosomes, clearly differing from the previous species. These results are discussed in order to get an insight into the main trends of the chromosomal evolution in Timarcha. PMID- 27186336 TI - Chromosomal evidence of species status and evolutionary relationships of the black fly Prosimulium petrosum (Diptera, Simuliidae) in Armenia. AB - The karyotype of Armenian populations of the black fly Prosimulium petrosum Rubtsov, 1955 was characterized and compared with that of all other chromosomally known Palearctic members of the Prosimulium hirtipes group. Analysis of the polytene chromosomes established that Prosimulium petrosum is most closely related to European populations of Prosimulium latimucro (Enderlein, 1925) with which it shares an identical fixed chromosomal banding sequence. Its validity as a species, separate from Prosimulium latimucro, is based on its unique sex differential sections in the expanded centromere region of chromosome I, in agreement with the unique structural configuration of the hypostomal teeth of its larvae. Prosimulium petrosum and Prosimulium latimucro, therefore, are homosequential species, demonstrating the value of a combined chromosomal and morphological approach in determining species status. PMID- 27186337 TI - Sex chromosome diversity in Armenian toad grasshoppers (Orthoptera, Acridoidea, Pamphagidae). AB - Although previous cytogenetic analysis of Pamphagidae grasshoppers pointed to considerable karyotype uniformity among most of the species in the family, our study of species from Armenia has discovered other, previously unknown karyotypes, differing from the standard for Pamphagidae mainly in having unusual sets of sex chromosomes. Asiotmethis turritus (Fischer von Waldheim, 1833), Paranocaracris rubripes (Fischer von Waldheim, 1846), and Nocaracris cyanipes (Fischer von Waldheim, 1846) were found to have the karyotype 2n?=16+neo-XY and 2n?=16+neo-XX, the neo-X chromosome being the result of centromeric fusion of an ancient acrocentric X chromosome and a large acrocentric autosome. The karyotype of Paranothrotes opacus (Brunner von Wattenwyl, 1882) was found to be 2n?=14+X1X2Y and 2n?=14+X1X1X2X2., the result of an additional chromosome rearrangement involving translocation of the neo-Y and another large autosome. Furthermore, evolution of the sex chromosomes in these species has involved different variants of heterochromatinization and miniaturization of the neo-Y. The karyotype of Eremopeza festiva (Saussure, 1884), in turn, appeared to have the standard sex determination system described earlier for Pamphagidae grasshoppers, 2n?=18+X0 and 2n?=18+XX, but all the chromosomes of this species were found to have small second C-positive arms. Using fluorescent in situ hybridization (FISH) with 18S rDNA and telomeric (TTAGG)n DNA repeats to yield new data on the structural organization of chromosomes in the species studied, we found that for most of them, clusters of repeats homologous to 18S rDNA localize on two, three or four pairs of autosomes and on the X. In Eremopeza festiva, however, FISH with labelled 18S rDNA painted C-positive regions of all autosomes and the X chromosome; clusters of telomeric repeats localized primarily on the ends of the chromosome arms. Overall, we conclude that the different stages of neo-Y degradation revealed in the Pamphagidae species studied make the family a very promising and useful model for studying sex chromosome evolution. PMID- 27186338 TI - Identification of homogeneously staining regions by G-banding and chromosome microdissection, and FISH marker selection using human Alu sequence primers in a scleractinian coral Coelastrea aspera Verrill, 1866 (Cnidaria). AB - Karyotype analysis was performed on the scleractinian coral Coelastrea aspera Verrill, 1866, commonly found along temperate coasts in Japan (30-35 degrees N) and in coastal waters in the Indian and Pacific oceans. G-banding of Coelastrea aspera was successfully performed, although the banding pattern was not as clear as that in mammals. The karyogram clearly revealed that this coral had a homogeneously staining region (hsr) in chromosome 11. This hsr consisted of ribosomal RNA (rRNA) related genes, which was demonstrated by fluorescence in situ hybridization (FISH) with probes generated using 28S ribosomal DNA (rDNA) primers and those generated through chromosome microdissection. In addition, we conducted silver-stained nucleolus organizer region (Ag-NOR) analysis and found Ag depositions in the interphase nuclei but not on rRNA gene loci and hsr(s) in the mitotic stage. The hsr of this coral was observed in approximately 50% of the metaphase spreads analyzed. This may explain the diversity of coral rDNA based on the molecular study of sequence analysis. Furthermore, it was discovered that human telomere and Alu repeated sequences were present in this Coelastrea aspera. Probes derived from human Alu sequences are expected to play an important role in the classification of corals. Overall, our data can be of great value in discriminating among scleractinian coral species and understanding their genetics, including chromosomal evolution. PMID- 27186339 TI - Evolutionary trends in the family Curimatidae (Characiformes): inferences from chromosome banding. AB - The family Curimatidae is a fish group usually considered chromosomally conserved in their diploid number. However, some studies show small changes in the karyotype microstructure, and the presence of B chromosomes, indicating a chromosomal diversification within the group, even if structural changes in the karyotypes are not visible. Few studies associate this trait with an evolutionary pattern within the family. This study aimed to characterize the karyotype, nucleolus organizer regions (NORs), and heterochromatin distribution of six species of Curimatidae of the genera Cyphocharax Fowler, 1906 and Steindachnerina Fowler, 1906: Cyphocharax voga (Hensel, 1870), Cyphocharax spilotus (Vari, 1987), Cyphocharax saladensis (Meinken, 1933), Cyphocharax modestus (Fernandez-Yepez, 1948), Steindachnerina biornata (Braga et Azpelicueta, 1987) and Steindachnerina insculpta (Fernandez-Yepez, 1948) and contribute data to a better understanding of the mechanisms involved in the chromosomal evolution of this group of fish. All specimens had 2n=54, m-sm, and B microchromosomes. Five species exhibited single NORs, except for Steindachnerina biornata, which showed a multiple pattern of ribosomal sites. NORs were chromomycin A3 positive (CMA3 (+)) and 4'-6-diamino 2-phenylindole (DAPI(-)) negative, exhibiting differences in the pair and chromosomal location of each individual of the species. FISH with 5S rDNA probe revealed sites in the pericentrometic position of a pair of chromosomes of five species. However, another site was detected on a metacentric chromosome of Cyphocharax spilotus. Heterochromatin distributed both in the pericentromeric and some terminal regions was revealed to be CMA3 (+)/DAPI(-). These data associated with the previously existing ones confirm that, although Curimatidae have a very conservative karyotype macrostructure, NORs and heterochromatin variability are caused by mechanisms of chromosome alterations, such as translocations and/or inversions, leading to the evolution and diversification of this group of fish. PMID- 27186340 TI - The contribution of cytogenetics and flow cytometry for understanding the karyotype evolution in three Dorstenia (Linnaeus, 1753) species (Moraceae). AB - Chromosome morphometry and nuclear DNA content are useful data for cytotaxonomy and for understanding the evolutionary history of different taxa. However, the chromosome number is the only karyotype aspect reported for the species of Dorstenia so far. In this study, the nuclear genome size of Dorstenia arifolia (Lamarck, 1786), Dorstenia bonijesu (Carauta & C. Valente, 1983) and Dorstenia elata (Hooker, 1840) was evaluated and their karyotype morphometry accomplished, with the aim of verifying the potential of those parameters to understand evolutionary issues. Mean nuclear 2C value ranged from 2C = 3.49 picograms (pg) for Dorstenia elata to 2C = 5.47 pg for Dorstenia arifolia, a variation of +/- 1.98 pg. Even though showing a marked difference in 2C value, the three species exhibited the same 2n = 32. Corroborating the flow cytometry data, differences in chromosome morphology were found among the karyotypes of the species investigated. Based on this and the only phylogeny proposed for Dorstenia thus far, structural rearrangements are related to the karyotype variations among the three species. Besides, the karyological analysis suggests a polyploid origin of the Dorstenia species studied here. PMID- 27186341 TI - Karyotype of three Lonchophylla species (Chiroptera, Phyllostomidae) from Southeastern Brazil. AB - Lonchophylla Thomas, 1903 is a Neotropical bat genus that comprises 12 species, with little cytogenetic information available. Here we present the description of the karyotype of three species collected in Southeastern Brazil. Lonchophylla bokermanni Sazima, Vizotto & Taddei, 1978, Lonchophylla dekeyseri Taddei, Vizotto & Sazima, 1983, and Lonchophylla peracchii Dias, Moratelli & Esberard, 2013 showed the same diploid number 2n = 28 and the same autosomal fundamental number FNa = 50, in both Lonchophylla bokermanni and Lonchophylla peracchii. We observed that the karyotypes were also cytogenetically similar when we compared the studied species with other species within the same genus. It is therefore not possible to differentiate the species using only karyotypes with conventional staining. However, this information increases the knowledge of the genus and can be one more important character for a better phylogenetic comprehension of this taxon. PMID- 27186342 TI - Refinement of the karyological aspects of Psidium guineense (Swartz, 1788): a comparison with Psidium guajava (Linnaeus, 1753). AB - Euploidy plays an important role in the evolution and diversification of Psidium Linnaeus, 1753. However, few data about the nuclear DNA content, chromosome characterization (morphometry and class) and molecular markers have been reported for this genus. In this context, the present study aims to shed light on the genome of Psidium guineense Swartz, 1788, comparing it with Psidium guajava Linnaeus, 1753. Using flow cytometry, the nuclear 2C value of Psidium guineense was 2C = 1.85 picograms (pg), and the karyotype showed 2n = 4x = 44 chromosomes. Thus, Psidium guineense has four chromosome sets, in accordance with the basic chromosome number of Psidium (x = 11). In addition, karyomorphometric analysis revealed morphologically identical chromosome groups in the karyotype of Psidium guineense. The high transferability of microsatellites (98.6%) further corroborates with phylogenetic relationship between Psidium guajava and Psidium guineense. Based on the data regarding nuclear genome size, karyotype morphometry and molecular markers of Psidium guineense and Psidium guajava (2C = 0.95 pg, 2n = 2x = 22 chromosomes), Psidium guineense is a tetraploid species. These data reveal the role of euploidy in the diversification of the genus Psidium. PMID- 27186343 TI - Chromosomal variation in Argentine populations of Akodon montensis Thomas, 1913 (Rodentia, Cricetidae, Sigmodontinae). AB - The genus Akodon Meyen, 1833 is one of the most species-rich among sigmodontine rodents and has great chromosome variability. Akodon montensis has a relatively broad distribution in South America, and Argentine populations are located in the southernmost region of its range. Brazilian populations have important chromosomal variability, but cytogenetic data from Argentina are scarce. We performed a chromosome characterization of natural populations of Akodon montensis using conventional staining, C-banding, Ag-NORs and base-specific fluorochromes. A total of 31 specimens from five localities of Misiones Province, in Argentina, were analyzed. The 2n=24 chromosomes was the most frequently observed karyotype. However, five individuals presented 25 chromosomes due to a supernumerary B-chromosome; and one individual had 2n=26 due to one B plus a trisomy for chromosome 11. Additionally, two XY females and two variants of the X chromosomes were found. C-positive centromeric bands occurred in all chromosomes; additional C-bands were observed in some autosomes, the X, Y and B chromosomes. Ag-NORs were observed in five autosomes, and the B chromosome was frequently marked. Fluorochrome banding was similar among karyotypes of the analyzed populations. Comparisons of cytogenetic data among populations of Argentina and Brazil showed the presence of high intraspecific variability in Akodon montensis and some differences among regions. PMID- 27186344 TI - Cytogenetic characterization and B chromosome diversity in direct-developing frogs of the genus Oreobates (Brachycephaloidea, Craugastoridae). AB - Oreobates Jimenez de la Espada, 1872 is a large group of South American frogs with terrestrial reproduction and direct development, located in the superfamily Brachycephaloidea. About 260 brachycephaloidean species have been cytogenetically studied so far, at least with standard techniques. However, this information represents fewer than 17% species of the family Craugastoridae Hedges, Duellman & Heinicke, 2008, where the genus Oreobates is included. In the present work, using a diversity of standard and molecular techniques, we describe the karyotype of Oreobates barituensis Vaira & Ferrari, 2008, Oreobates berdemenos Pereyra, Cardozo, Baldo & Baldo, 2014 and Oreobates discoidalis (Peracca, 1895), from northwestern Argentina. The three species analyzed showed a diploid karyotype with 2n = 22 biarmed chromosomes, fundamental number (FN) = 44, nucleolus organizer regions (NORs) located pericentromerically on pair 7, and a centromeric and pericentromeric C-banding pattern. We observed variations in the chromosome number in Oreobates barituensis due the presence of two morphs of B chromosomes, one medium-sized telocentric (BT) and another subtelocentric and smaller (Bst). Both B chromosomes are mitotically stable and were recorded in all somatic and germinal cells analyzed. The BT chromosome occurred at a maximum of one per individual (2n = 22+BT), and the other one was observed single (2n = 22 + Bst) or as a pair in two doses (2n = 22 + 2BT). We additionally observed other supernumerary chromosomes in the three species analyzed, all of them euchromatic, small, dot-shaped and with instability during mitoses, showing a frequency of occurrence below 50% in studied specimens. The occurrence of polymorphic and spontaneous chromosomal rearrangements and supernumerary chromosomes is a recurrent feature reported in frogs with terrestrial habits (Brachycephaloidea and Hemiphractidae Peters, 1862), which suggests that Brachycephaloidea may be a promising group for studying the origin and maintenance of B chromosomes in anurans. PMID- 27186345 TI - Chromosomal mapping of tandem repeats in the Yesso Scallop, Patinopecten yessoensis (Jay, 1857), utilizing fluorescence in situ hybridization. AB - Construction of cytogenetic maps can provide important information for chromosome identification, chromosome evolution and genomic research. However, it hasn't been conducted in many scallop species yet. In the present study, we attempted to map 12 fosmid clones containing tandem repeats by fluorescence in situ hybridization (FISH) in the Yesso scallop Patinopecten yessoensis (Jay, 1857). The results showed 6 fosmid clones were successfully mapped and distributed in 6 different pairs of chromosomes. Three clones were respectively assigned to a pair of metacentric chromosomes, a pair of submetacentric chromosomes and a pair of telocentric chromosomes and the remaining 3 clones showed their loci on three different pairs of subtelocentric chromosomes by co-hybridization. In summary, totally 8 pairs of chromosomes of the Yesso scallop were identified by 6 fosmid clones and two rDNA probes. Furthermore, 6 tandem repeats of 5 clones were sequenced and could be developed as chromosome specific markers for the Yesso scallop. The successful localization of fosmid clones will undoubtedly facilitate the integration of linkage groups with cytogenetic map and genomic research for the Yesso scallop. PMID- 27186346 TI - Karyological investigations and new chromosome number reports in Bellevalia Lapeyrouse, 1808 and Muscari Miller, 1758 (Asparagaceae) from Algeria. AB - Karyological investigations were carried out on four species of Bellevalia Lapeyrouse, 1808 and Muscari Miller, 1758 (Asparagaceae) sampled in contrasting bioclimatic conditions of Algeria. The endemic Bellevalia mauritanica Pomel, 1874 was found to have a tetraploid cytotype 2n = 4x = 16 and an octoploid 2n = 8x = 32 which is a new report. The chromosome number 2n = 2x = 18 in Muscari comosum (Linnaeus, 1753) Miller, 1768 and Muscari maritimum Desfontaines, 1798 was in conformity with earlier reports. The latter species reveals a lesser bimodality of the karyotype. Within Muscari neglectum Gussone ex Tenore, 1842 pentaploid (2n = 5x = 45), hexaploid (2n = 6x = 54) and very rare octoploid cytotype (2n = 8x = 72) have been reported in Algeria. Principal component analysis performed on basis of karyotype parameters, showed a segregation of the different cytotypes. This study provides new karyological information, which is discussed in a taxonomic context. PMID- 27186347 TI - A chromosomal analysis of eleven species of Gyrinidae (Coleoptera). AB - Karyotypes are presented for 10 species of Gyrinus Geoffroy, 1762: Gyrinus minutus Fabricius, 1798, Gyrinus caspius Menetries, 1832, Gyrinus paykulli Ochs, 1927, Gyrinus distinctus Aube, 1836 var. fairmairei Regimbart, 1883, Gyrinus marinus Gyllenhal, 1808, Gyrinus natator (Linnaeus, 1758), Gyrinus opacus Sahlberg, 1819, Gyrinus substriatus Stephens, 1869, Gyrinus suffriani Scriba, 1855, Gyrinus urinator Illiger, 1807 and for Orectochilus villosus (Muller, 1776) (Coleoptera: Gyrinidae). The 10 Gyrinus species have karyotypes comprising 13 pairs of autosomes plus sex chromosomes which are X0 (?), XX (?), with the X chromosomes the longest in the nucleus. Orectochilus villosus has 16 pairs of autosomes plus X0, XX sex chromosomes. The data obtained by Saxod and Tetart (1967) and Tetart and Saxod (1968) for five of the Gyrinus species are compared with our results. Saxod and Tetart considered the X chromosome to be the smallest in the nucleus in all cases, and this is considered to result from confusion arising from uneven condensation of some of the chromosomes. Small differences between the chromosomes of different Gyrinus species have been detected, but not between Greenland and Swedish populations of Gyrinus opacus, nor between typical Gyrinus distinctus from France and Gyrinus distinctus var. fairmairei from Kuwait. PMID- 27186348 TI - Discovery of gastric inhibitory polypeptide and its subsequent fate: Personal reflections. AB - The present review focuses initially on experimental studies that were designed to identify acid inhibitory factors, referred to as 'enterogastrones,' that ultimately led to the isolation of gastric inhibitory polypeptide (GIP), a 42 amino acid polypeptide. GIP was shown to inhibit acid secretion in animal models, as well as stimulating gastric somatostatin secretion. However, its role in human gastric physiology is unclear. Further studies showed that GIP strongly stimulated the secretion of insulin, in the presence of elevated glucose, and this 'incretin' action is now considered to be its most important; an alternative for the GIP acronym, glucose-dependent insulinotropic polypeptide, was therefore introduced. In the 1970s, GIP purified by conventional chromatography was shown by high-performance liquid chromatography to consist largely of GIP 1-42 and GIP 3-42. It was later shown that dipeptidyl peptidase 4 was a physiologically relevant enzyme responsible for this conversion, as well as the similar metabolism of the second incretin, glucagon-like peptide-1. Dipeptidyl peptidase 4 inhibitors are currently in use as type 2 diabetes therapeutics, and studies on islet transplantation in rodent models of type 1 diabetes have shown that dipeptidyl peptidase-4 inhibitor treatment reduces graft rejection. Additional studies on C-terminally shortened forms of GIP have shown that GIP 1-30 and a dipeptidyl peptidase-4-resistant form (D-Ala(2) GIP 1-30) are equipotent to the intact polypeptide in vitro, and administration of D-Ala(2) GIP 1-30 to diabetic rodents greatly improved glucose tolerance and reduced apoptotic cell death in islet beta-cells. There are probably therefore further clinically useful effects of GIP that require investigation. PMID- 27186349 TI - Searching for the physiological role of glucose-dependent insulinotropic polypeptide. AB - Glucose-dependent insulinotropic polypeptide (GIP) was established as a gut hormone more than 40 years ago, and there is good experimental support for its role as an incretin hormone although deletion of the GIP receptor or the GIP cells or GIP receptor mutations have only minor effects on glucose metabolism. Unlike the related hormone, GLP-1, GIP stimulates the secretion of glucagon, which in healthy individuals may help to stabilize glucose levels, but in people with type 2 diabetes may contribute to glucose intolerance. A role in lipid metabolism is supported by numerous indirect observations and by resistance to diet-induced obesity after deletion of the GIP receptor. However, a clear effect on lipid clearance could not be identified in humans, raising doubt about its importance. The GIP receptor is widely expressed in the body and also appears to be expressed on bone cells, and experimental studies in rodent point to effects on bone metabolism. Recent studies revealed pronounced inhibitory effects of GIP on bone resorption markers in humans and suggest that GIP may be (one of the) gastrointestinal regulators of bone turn-over. In support of this, a loss-of function GIP receptor mutation in humans is associated with a marked increase in fracture risk. The lack of a reliable GIP receptor antagonist contributes to the uncertainty regarding the physiological role of GIP. PMID- 27186350 TI - Mechanisms underlying glucose-dependent insulinotropic polypeptide and glucagon like peptide-1 secretion. AB - The incretin hormones, glucose-dependent insulinotropic peptide and glucagon-like peptide-1, are secreted from intestinal K- and L cells, respectively, with the former being most abundant in the proximal small intestine, whereas the latter increase in number towards the distal gut. Although an overlap between K- and L cells can be observed immunohistochemically or in murine models expressing fluorescent markers under the control of the two hormone promoters, the majority (>80%) of labeled cells seems to produce only one of these hormones. Transcriptomic analysis showed a close relationship between small intestinal K- and L cells, and glucose sensing mechanisms appear similar in both cell types with a predominant role of electrogenic glucose uptake through sodium-coupled glucose transporter 1. Similarly, both cell types produce the long-chain fatty acid sensing G-protein-coupled receptors, FFAR1 (GPR40) and FFAR4 (GPR120), but differ in the expression/functionality of other lipid sensing receptors. GPR119 and FFAR2/3, for example, have clearly documented roles in glucagon-like peptide 1 secretion, whereas agonists for the endocannabinoid receptor type 1 have been found to show largely selective inhibition of glucose-dependent insulinotropic peptide secretion. In conclusion, although K- and L cell populations overlap and share key molecular nutrient-sensing mechanisms, subtle differences between the responsiveness of the different cell types might be exploited to differentially modulate glucose-dependent insulinotropic peptide or glucagon-like peptide-1 secretion. PMID- 27186351 TI - Mechanisms of fat-induced gastric inhibitory polypeptide/glucose-dependent insulinotropic polypeptide secretion from K cells. AB - Gastric inhibitory polypeptide/glucose-dependent insulinotropic polypeptide (GIP) is one of the incretins, which are gastrointestinal hormones released in response to nutrient ingestion and potentiate glucose-stimulated insulin secretion. Single fat ingestion stimulates GIP secretion from enteroendocrine K cells; chronic high fat diet (HFD) loading enhances GIP secretion and induces obesity in mice in a GIP-dependent manner. However, the mechanisms of GIP secretion from K cells in response to fat ingestion and GIP hypersecretion in HFD-induced obesity are not well understood. We generated GIP-green fluorescent protein knock-in (GIP (gfp/+)) mice, in which K cells are labeled by enhanced GIP-green fluorescent protein. Microarray analysis of isolated K cells from GIP (gfp/+) mice showed that both fatty acid-binding protein 5 and G protein-coupled receptor 120 are highly expressed in K cells. Single oral administration of fat resulted in significant reduction of GIP secretion in both fatty acid-binding protein 5- and G protein-coupled receptor 120-deficient mice, showing that fatty acid-binding protein 5 and G protein-coupled receptor 120 are involved in acute fat-induced GIP secretion. Furthermore, the transcriptional factor, regulatory factor X6 (Rfx6), is highly expressed in K cells. In vitro experiments using the mouse enteroendocrine cell line, STC-1, showed that GIP messenger ribonucleic acid levels are upregulated by Rfx6. Expression levels of Rfx6 messenger ribonucleic acid as well as that of GIP messenger ribonucleic acid were augmented in the K cells of HFD-induced obese mice, in which GIP content in the small intestine is increased compared with that in lean mice fed a control diet. These results suggest that Rfx6 is involved in hypersecretion of GIP in HFD-induced obese conditions by increasing GIP gene expression. PMID- 27186352 TI - Carbohydrate-induced secretion of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1. AB - Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are the incretin hormones secreted from enteroendocrine K-cells and L cells, respectively, by oral ingestion of various nutrients including glucose. K cells, L-cells and pancreatic beta-cells are glucose-responsive cells with similar glucose-sensing machinery including glucokinase and an adenosine triphosphate-sensitive K(+) channel comprising KIR6.2 and sulfonylurea receptor 1. However, the physiological role of the adenosine triphosphate-sensitive K(+) channel in GIP secretion in K-cells and GLP-1 secretion in L-cells is not elucidated. Recently, it was reported that GIP and GLP-1-producing cells are present also in pancreatic islets, and islet-derived GIP and GLP-1 contribute to glucose-induced insulin secretion from pancreatic beta-cells. In this short review, we focus on GIP and GLP-1 secretion by monosaccharides, such as glucose or fructose, and the role of the adenosine triphosphate-sensitive K(+) channel in GIP and GLP-1 secretion. PMID- 27186353 TI - Alternative form of glucose-dependent insulinotropic polypepide and its physiology. AB - Glucose-dependent insulinotropic polypepide (GIP) was first extracted from porcine gut mucosa and identified as "incretin" decades ago. Though early studies have shown the possible GIP isoforms by gel filtration profiles from porcine or human intestinal extracts analyzed by radioimmunoassay (RIA), GIP is currently believed to consist of 42 amino acids (GIP1-42), which are released from gut K cells and promote postprandial insulin release. In fact, GIP1-42 is usually processed from proGIP by the action of prohormone convertase (PC) 1/3 in the gut. GIP expression is occasionally found in the intestinal glucagon-like peptide-1 secreting cells, suggesting gene expression of both GIP and proglucagon can co exist in identical cells. However, GIP1-42 immunoreactivity is rarely found in alpha-cells or other pancreatic endocrine cells of wild-type mammals. Interestingly, we found that short-form GIP1-30 is expressed in and released from pancreatic alpha-cells and a subset of enteroendocrine cells through proGIP processing by PC2. GIP1-30 is also insulinotropic and modulates glucose stimulated insulin secretion in a paracrine manner. It is also suggested that short-form GIP1-30 possibly plays a crucial role for the islet development. It has not been well elucidated whether expression of GIP1-30 is modulated in the diabetic status, and whether GIP1-30 might have therapeutic potentials. Our preliminary data suggest that short-form GIP1-30 might play important roles in glucose metabolism. PMID- 27186354 TI - beta-Cell glutamate signaling: Its role in incretin-induced insulin secretion. AB - Insulin secretion from the pancreatic beta-cell (referred to as beta-cell hereafter) plays a central role in glucose homeostasis. Impaired insulin secretion is a major factor contributing to the development of diabetes and, therefore, is an important target for treatment of the disease. Cyclic adenosine monophosphate is a key second messenger in beta-cells that amplifies insulin secretion. Incretins released by the gut potentiate insulin secretion through cyclic adenosine monophosphate signaling in beta-cells, which is the basis for the incretin-based diabetes therapies now being used worldwide. Despite its importance, the interaction between glucose metabolism and incretin/cyclic adenosine monophosphate signaling in beta-cells has long been unknown. A recent study showed that cytosolic glutamate produced by glucose metabolism in beta cells is a key signal in incretin-induced insulin secretion. Here we review the physiological and pathophysiological roles of beta-cell glutamate signaling in incretin-induced insulin secretion. PMID- 27186355 TI - Glucagon-like peptide-1 and cholecystokinin production and signaling in the pancreatic islet as an adaptive response to obesity. AB - Precise control of blood glucose is dependent on adequate beta-cell mass and function. Thus, reductions in beta-cell mass and function lead to insufficient insulin production to meet demand, and result in diabetes. Recent evidence suggests that paracrine signaling in the islet might be important in obesity, and disruption of this signaling could play a role in the pathogenesis of diabetes. For example, we recently discovered a novel islet incretin axis where glucagon like peptide-1 regulates beta-cell production of another classic gut hormone, cholecystokinin. This axis is stimulated by obesity, and plays a role in enhancing beta-cell survival. In the present review, we place our observations in the wider context of the literature on incretin regulation in the islet, and discuss the potential for therapeutic targeting of these pathways. PMID- 27186356 TI - Is GLP-1 a hormone: Whether and When? AB - Glucagon-like peptide-1 (GLP-1) is a product of proglucagon cleavage synthesized in L cells in the intestinal mucosa, alpha-cells in the pancreatic islet, and neurons in the nucleus of the solitary tract. GLP-1 is essential for normal glucose tolerance and acts through a specific GLP-1 receptor that is expressed by islet beta-cells as well as other cell types. Because plasma concentrations of GLP-1 increase following meal ingestion it has been generally presumed that GLP-1 acts as a hormone, communicating information from the intestine to the endocrine pancreas through the circulation. However, there are a number of problems with this model including low circulating concentrations of GLP-1 in plasma, limited changes after meal ingestion and rapid metabolism in the plasma. Moreover, antagonism of systemic GLP-1 action impairs insulin secretion in the fasting state, suggesting that the GLP-1r is active even when plasma GLP-1 levels are low and unchanging. Consistent with these observations, deletion of the GLP-1r from islet beta-cells causes intolerance after IP or IV glucose, challenges that do not induce GLP-1 secretion. Taken together, these data support a model whereby GLP-1 acts through neural or paracrine mechanisms to regulate physiologic insulin secretion. In contrast, bariatric surgery seems to be a condition in which circulating GLP-1 could have an endocrine effect. Both gastric bypass and sleeve gastrectomy are associated with substantial increases in postprandial GLP-1 release and in these conditions interference with GLP-1r signaling has a significant impact on glucose regulation after eating. Thus, with either bariatric surgery or treatment with long-acting GLP-1r agonists, circulating peptide mediates insulinotropic activity. Overall, a case can be made that physiologic actions of GLP-1 are not hormonal, but that an endocrine mechanism of GLP-1r activation can be co-opted for therapeutics. PMID- 27186357 TI - Long-acting glucagon-like peptide-1 receptor agonists have direct access to and effects on pro-opiomelanocortin/cocaine- and amphetamine-stimulated transcript neurons in the mouse hypothalamus. AB - Liraglutide is a glucagon-like peptide-1 receptor (GLP-1R) agonist marketed for the treatment of type 2 diabetes. Besides lowering blood glucose, liraglutide reduces bodyweight, and has recently also been approved for the obesity indication. Acutely, GLP-1 markedly reduces gastric emptying, and this effect was previously believed to at least partly explain the effect on bodyweight loss. However, recent studies in both humans and animals have shown that GLP-1R agonists, such as liraglutide, that lead to pharmacological concentrations for 24 h/day only have a minor effect on gastric emptying; such an effect is unlikely to have lasting effects on appetite reduction. Liraglutide has been shown to have direct effects in the arcuate nucleus of the rodent brain, activating pro opiomelanocortin neurons and increasing levels of the cocaine- and amphetamine stimulated transcript neuropeptide messenger ribonucleic acid, which correlate nicely to clinical studies where liraglutide was shown to increase feelings of satiety. However, despite the lack of a GLP-1R on agouti-related peptide/neuropeptide Y neurons, liraglutide also was able to prevent a hunger associated increase in agouti-related peptide and neuropeptide Y neuropeptide messenger ribonucleic acid, again with a strong correlation to clinical studies that document reduced hunger feelings in patients while taking liraglutide. Studies using fluorescent labeled liraglutide, as well as other GLP-1R agonists, and analysis using single-plane illumination microscopy show that such medium sized peptide-based compounds can directly access not only circumventricular organs of the brain, but also directly access discrete regions in the hypothalamus. The direct effects of long-acting GLP-1R agonists in the hypothalamus are likely to be an important new pathway in understanding GLP-1R agonist mediated weight loss. PMID- 27186358 TI - Neural effects of gut- and brain-derived glucagon-like peptide-1 and its receptor agonist. AB - Glucagon-like peptide-1 (GLP-1) is derived from both the enteroendocrine L cells and preproglucagon-expressing neurons in the nucleus tractus solitarius (NTS) of the brain stem. As GLP-1 is cleaved by dipeptidyl peptidase-4 yielding a half life of less than 2 min, it is plausible that the gut-derived GLP-1, released postprandially, exerts its effects on the brain mainly by interacting with vagal afferent neurons located at the intestinal or hepatic portal area. GLP-1 neurons in the NTS widely project in the central nervous system and act as a neurotransmitter. One of the physiological roles of brain-derived GLP-1 is restriction of feeding. GLP-1 receptor agonists have recently been used to treat type 2 diabetic patients, and have been shown to exhibit pleiotropic effects beyond incretin action, which involve brain functions. GLP-1 receptor agonist administered in the periphery is stable because of its resistance to dipeptidyl peptidase-4, and is highly likely to act on the brain by passing through the blood-brain barrier (BBB), as well as interacting with vagal afferent nerves. Central actions of GLP-1 have various roles including regulation of feeding, weight, glucose and lipid metabolism, cardiovascular functions, cognitive functions, and stress and emotional responses. In the present review, we focus on the source of GLP-1 and the pathway by which peripheral GLP-1 informs the brain, and then discuss recent findings on the central effects of GLP-1 and GLP-1 receptor agonists. PMID- 27186359 TI - Glucagon-like peptide-1: The missing link in the metabolic clock? AB - Circadian expression of clock genes in peripheral tissues is critical to the coordinated regulation of intestinal digestive and absorptive functions, insulin secretion, and peripheral tissue nutrient deposition during periods of nutrient ingestion, thereby preventing metabolic dysregulation. As glucagon-like peptide-1 is a key incretin hormone that regulates glucose-dependent insulin secretion, we hypothesized that this intestinal hormone is a player in the peripheral metabolic clock, linking nutrient ingestion to insulin secretion. We have now established that secretion of glucagon-like peptide-1 from the intestinal L cell shows a rhythmic pattern in rats and humans in vivo that is altered by circadian disruptors, such as constant light exposure, consumption of a Western diet and feeding at inappropriate times (i.e., during the light period in rodents). Interestingly, the alterations in the rhythm of the glucagon-like peptide-1 secretory responses were found to parallel the changes in the pattern of insulin responses in association with significant impairments in glucose tolerance. Furthermore, we have detected circadian clock gene expression, and showed circadian secretion of glucagon-like peptide-1 from both the murine and human L cell in vitro. These findings demonstrate that glucagon-like peptide-1 is a functional component of the peripheral metabolic clock, and suggest that altered release of glucagon-like peptide-1 might play a role in the metabolic perturbations that result from circadian disruption. PMID- 27186360 TI - Novel extrapancreatic effects of incretin. AB - The hormonal factors implicated as transmitters of signals from the gut to pancreatic beta-cells are referred to as incretins. Gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are incretins. In addition to the insulinotropic effects, we have shown, using the GIP receptor and GLP-1 receptor-deficient mice, that GIP and GLP-1 have direct actions on adipocytes and the kidney, respectively. Because GIP receptors and GLP-1 receptors are differentially expressed in a tissue-specific manner, GIP and GLP-1 have specific physiological activities, and further comprehensive characterization of the extrapancreatic actions of GIP and GLP-1 is anticipated, as dipeptidyl peptidase IV inhibitors activate both GIP and GLP-1 signaling. PMID- 27186361 TI - Anti-atherogenic and anti-inflammatory properties of glucagon-like peptide-1, glucose-dependent insulinotropic polypepide, and dipeptidyl peptidase-4 inhibitors in experimental animals. AB - We reported that native incretins, liraglutide and dipeptidyl peptidase-4 inhibitors (DPP-4i) all confer an anti-atherosclerotic effect in apolipoprotein E null (Apoe (-/-)) mice. We confirmed the anti-atherogenic property of incretin related agents in the mouse wire injury model, in which the neointimal formation in the femoral artery is remarkably suppressed. Furthermore, we showed that DPP 4i substantially suppresses plaque formation in coronary arteries with a marked reduction in the accumulation of macrophages in cholesterol-fed rabbits. DPP-4i showed an anti-atherosclerotic effect in Apoe (-/-) mice mainly through the actions of glucagon-like peptide-1 and glucose-dependent insulinotropic polypepide. However, the dual incretin receptor antagonists partially attenuated the suppressive effect of DPP-4i on atherosclerosis in diabetic Apoe (-/-) mice, suggesting an incretin-independent mechanism. Exendin-4 and glucose-dependent insulinotropic polypepide elicited cyclic adenosine monophosphate generation, and suppressed the lipopolysaccharide-induced gene expression of inflammatory molecules, such as interleukin-1beta, interleukin-6 and tumor necrosis factor alpha, in U937 human monocytes. This suppressive effect, however, was attenuated by an inhibitor of adenylate cyclase and mimicked by 8-bromo-cyclic adenosine monophosphate or forskolin. DPP-4i substantially suppressed the lipopolysaccharide-induced expression of inflammatory cytokines without affecting cyclic adenosine monophosphate generation or cell proliferation. DPP-4i more strongly suppressed the lipopolysaccharide-induced gene expression of inflammatory molecules than incretins, most likely through inactivation of CD26. Glucagon-like peptide-1 and glucose-dependent insulinotropic polypepide suppressed oxidized low-density lipoprotein-induced macrophage foam cell formation in a receptor-dependent manner, which was associated with the downregulation of acyl-coenzyme A cholesterol acyltransferase-1 and CD36, as well as the up-regulation of adenosine triphosphate-binding cassette transporter A1. Our studies strongly suggest that incretin-related agents have favorable effects on macrophage-driven atherosclerosis in experimental animals. PMID- 27186362 TI - Engineering the gut for insulin replacement to treat diabetes. AB - The gut epithelium's large surface area, its direct exposure to ingested nutrients, its vast stem cell population and its immunotolerogenic environment make it an excellent candidate for therapeutic cells to treat diabetes. Thus, several attempts have been made to coax immature gut cells to differentiate into insulin-producing cells by altering the expression patterns of specific transcription factors. Furthermore, because of similarities in enteroendocrine and pancreatic endocrine cell differentiation pathways, other approaches have used genetically engineered enteroendocrine cells to produce insulin in addition to their endogenous secreted hormones. Several studies support the utility of both of these approaches for the treatment of diabetes. Converting a patient's own gut cells into meal-regulated insulin factories in a safe and immunotolerogenic environment is an attractive approach to treat and potentially cure diabetes. Here, we review work on these approaches and indicate where we feel further advancements are required. PMID- 27186363 TI - Contribution of the distal small intestine to metabolic improvement after bariatric/metabolic surgery: Lessons from ileal transposition surgery. AB - Roux-en Y gastric bypass is a highly effective bariatric/metabolic surgical procedure that can induce robust weight loss and even remission of type 2 diabetes. One of the characteristic consequences of Roux-en Y gastric bypass is the expedited nutrient delivery to the distal small intestine, where L-cells are abundant and bile acid reabsorption occurs. To examine the role of the distal small intestine in isolation from other components of Roux-en Y gastric bypass, the ileal transposition (IT) surgery has been used in various rat models. IT relocates the distal ileal segment to the upper jejunum distal to the ligament of Treitz without any other alterations in the gastrointestinal anatomy. Therefore, IT exposes the distal ileal tissue to ingested nutrients after a meal faster than the normal condition. Although there is some inconsistency in the effect of IT according to different types of rat models and different types of surgical protocols, IT typically improved glucose tolerance, increased insulin sensitivity and induced weight loss, and the findings were more prominent in obese diabetic rats. Suggested mechanisms for the metabolic improvements after IT include increased L-cell secretion (e.g., glucagon-like peptides and peptide YY), altered bile acid metabolism, altered host-microbial interaction, attenuated metabolic endotoxemia and many others. Based on the effect of IT, we can conclude that the contribution of the distal small intestine to the metabolic benefits of bariatric/metabolic surgery is quite considerable. By unveiling the mechanism of action of IT, we might revolutionize the treatment for obesity and type 2 diabetes. PMID- 27186364 TI - Incretin-based drugs for type 2 diabetes: Focus on East Asian perspectives. AB - Type 2 diabetes in East Asians is characterized primarily by beta-cell dysfunction, and with less adiposity and less insulin resistance compared with that in Caucasians. Such pathophysiological differences can determine the appropriate therapeutics for the disease. Incretins, glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1, are secreted in response to meal ingestion, and enhance insulin secretion glucose-dependently. Incretin based drugs, dipeptidyl peptidase-4 inhibitors (DPP-4i) and glucagon-like peptide 1 receptor agonists, that ameliorate beta-cell dysfunction with limited hypoglycemia risk are now widely used in type 2 diabetes management. Recent meta analyses of clinical trials on DPP-4i and glucagon-like peptide-1 receptor agonists found that the drugs were more effective in Asians, most likely because of amelioration of beta-cell dysfunction. In addition, we found increased glycated hemoglobin-lowering effects of DPP-4i to be associated with intake of fish in type 2 diabetes, which suggests that dietary customs of East Asians might also underlie the greater efficacy of DPP-4i. Despite the limited risk, cases of severe hypoglycemia were reported for DPP-4i/sulfonylureas combinations. Importantly, hypoglycemia was more frequent in patients also receiving glibenclamide or glimepiride, which activate exchange protein directly activated by cyclic adenosine monophosphate 2, a critical mediator of incretin signaling, and was less frequent in patients receiving gliclazide, which does not activate exchange protein directly activated by cyclic adenosine monophosphate 2. Prevention of insulin-associated hypoglycemia by DPP-4i has gained attention with regard to the enhancement of hypoglycemia-induced glucagon secretion by insulinotropic polypeptide, but remains to be investigated in East Asians. Despite the safety issues, which are paramount and must be carefully monitored, the incretin-based drugs could have potential as a first choice therapy in East Asian type 2 diabetes patients. PMID- 27186365 TI - Spinal manipulative therapy, Graston technique(r) and placebo for non-specific thoracic spine pain: a randomised controlled trial. AB - BACKGROUND: Few controlled trials have assessed the efficacy of spinal manipulative therapy (SMT) for thoracic spine pain. No high quality trials have been performed to test the efficacy and effectiveness of Graston Technique(r) (GT), an instrument-assisted soft tissue therapy. The objective of this trial was to determine the efficacy of SMT and GT compared to sham therapy for the treatment of non-specific thoracic spine pain. METHODS: People with non-specific thoracic pain were randomly allocated to one of three groups: SMT, GT, or a placebo (de-tuned ultrasound). Each participant received up to 10 supervised treatment sessions at Murdoch University chiropractic student clinic over a 4 week period. The participants and treatment providers were not blinded to the treatment allocation as it was clear which therapy they were receiving, however outcome assessors were blinded and we attempted to blind the participants allocated to the placebo group. Treatment outcomes were measured at baseline, 1 week, and at one, three, six and 12 months. Primary outcome measures included a modified Oswestry Disability Index, and the Visual Analogue Scale (VAS). Treatment effects were estimated with intention to treat analysis and linear mixed models. RESULTS: One hundred and forty three participants were randomly allocated to the three groups (SMT = 36, GT = 63 and Placebo = 44). Baseline data for the three groups did not show any meaningful differences. Results of the intention to treat analyses revealed no time by group interactions, indicating no statistically significant between-group differences in pain or disability at 1 week, 1 month, 3 months, 6 months, or 12 months. There were significant main effects of time (p < 0.01) indicating improvements in pain and disability from baseline among all participants regardless of intervention. No significant adverse events were reported. CONCLUSION: This study indicates that there is no difference in outcome at any time point for pain or disability when comparing SMT, Graston Technique(r) or sham therapy for thoracic spine pain, however all groups improved with time. These results constitute the first from a fully powered randomised controlled trial comparing SMT, Graston technique(r) and a placebo. TRIAL REGISTRATION: This trial was registered with the Australia and New Zealand Clinical Trials Registry on the 7(th) February, 2008. TRIAL NUMBER: ACTRN12608000070336. PMID- 27186366 TI - Protein changes in abalone foot muscle from three geographical populations of Haliotis diversicolor based on proteomic approach. AB - Using two-dimensional gel electrophoresis, the foot muscle proteome of three geographical populations of Haliotis diversicolor were examined, with a total of 922 +/- 21 protein spots detected in the Japanese population (JJ), 904 +/- 25.6 in the Taiwanese population (TT), and 936 +/- 16.2 in the Vietnamese population (VV). Of these, 254 spots showed differential expression and 85 protein spots percentage volumes varied more than twofold. Both "genotype" and "spot" analysis of variance approaches significantly showed differences among the three populations. Hierarchical clustering analysis showed that TT and VV clustered together followed by clustering with JJ, which is consistent with their geographical location. Following matrix-assisted laser desorption/ionization time of-flight mass spectrometry, 30 differentially expressed proteins involved in major biological processes including energy production and storage and stress response were identified. Of these proteins, proteins pertaining to muscle contraction and muscle protein regulation showed highest expression levels in VV samples. Proteins involved in energy production and storage, including ATP synthase beta subunit, fructose-1,6-bisphosphate aldolase, arginine kinase, enolase, triosephosphate isomerase, and tauropine dehydrogenase, showed diverse expression patterns among the three populations. For stress-responsive proteins, the expression of heat shock protein 70 was JJ > VV > TT. The expression pattern of Cu/Zn-superoxide dismutase was JJ > VV > TT. Overall, these results may aid in the detection of new differentially expressed proteins within three different abalone populations. PMID- 27158444 TI - Adrenocorticotropic hormone gel in the treatment of systemic lupus erythematosus: A retrospective study of patients. AB - OBJECTIVES: Acthar Gel is a long-acting formulation of adrenocorticotropic hormone (ACTH) with anti-inflammatory effects thought to be mediated in part through melanocortin receptor activation. This study was initiated to understand the role of Acthar Gel in SLE treatment in rheumatology practices. METHODS: This is a retrospective case series of nine adult female patients treated with Acthar Gel for at least six months at five academic centers. Treating physicians completed a one-page questionnaire on lupus medications, disease activity, and outcomes. Clinical response was defined using SLEDAI 2K and improvement in the clinical manifestation(s) being treated. RESULTS: The most common clinical SLE manifestations/indications requiring therapy with Acthar Gel were arthritis, rash, and inability to taper corticosteroids. The mean SLEDAI 2K score at baseline was 5.8 +/- 5.0 (range 0-16). Six patients were concomitantly treated with corticosteroids (mean dose 18.3mg/day). All patients were on background SLE medications including immunosuppressives. Seven of nine patients had an overall improvement, with a decrease in SLEDAI 2K from 5.8 +/- 5.0 at baseline to 3.5 +/- 2.7 (range 0-8); four of five patients had improvement or resolution in arthritis, and one of two patients had resolution of inflammatory rash. Four patients discontinued corticosteroids and one patient tapered below 50% of the initial dose by 3 months of treatment with Acthar Gel. No adverse events were reported. CONCLUSIONS: This study suggests a role for Acthar Gel as an alternative to corticosteroids in the treatment of SLE. Acthar Gel appears to be safe and well-tolerated after 6 months of treatment, with a significant reduction in disease activity. PMID- 27186367 TI - Do relaxed selection and habitat temperature facilitate biased mitogenomic introgression in a narrowly endemic fish? AB - Introgression might be exceptionally common during the evolution of narrowly endemic species. For instance, in the springs of the small and isolated Cuatro Cienegas Valley, the mitogenome of the cichlid fish Herichthys cyanoguttatus could be rapidly introgressing into populations of the trophically polymorphic H. minckleyi. We used a combination of genetic and environmental data to examine the factors associated with this mitochondrial introgression. A reduced representation library of over 6220 single nucleotide polymorphisms (SNPs) from the nuclear genome showed that mitochondrial introgression into H. minckleyi is biased relative to the amount of nuclear introgression. SNP assignment probabilities also indicated that cichlids with more hybrid ancestry are not more commonly female providing no support for asymmetric backcrossing or hybrid induced sex-ratio distortion in generating the bias in mitochondrial introgression. Smaller effective population size in H. minckleyi inferred from the SNPs coupled with sequences of all 13 mitochondrial proteins suggests that relaxed selection on the mitogenome could be facilitating the introgression of "H. cyanoguttatus" haplotypes. Additionally, we showed that springs with colder temperatures had greater amounts of mitochondrial introgression from H. cyanoguttatus. Relaxed selection in H. minckleyi coupled with temperature-related molecular adaptation could be facilitating mitogenomic introgression into H. minckleyi. PMID- 27186369 TI - Meta-analysis of proportion estimates of Extended-Spectrum-Beta-Lactamase producing Enterobacteriaceae in East Africa hospitals. AB - BACKGROUND: A high proportion of Extended-Spectrum-Beta-Lactamase (ESBL) producing Enterobacteriaceae is causing common infections in all regions of the world. The burden of antibiotic resistance due to ESBL in East Africa is large but information is scarce and thus it is unclear how big the problem really is. To gain insight into the magnitude and molecular epidemiology of ESBL-producing Enterobacteriaceae in East Africa a literature search was performed in PubMed on 31 July 2015 to retrieve articles with relevant information on ESBL. METHODS AND RESULTS: Meta-analysis was performed to determine overall proportion estimate of ESBL-producing Enterobacteriaceae. A total of 4076 bacterial isolates were included in the analysis. The overall pooled proportion of ESBL-producing Enterobacteriaceae among included surveys done in East African hospitals was found to be 0.42 (95 % CI: 0.34-0.50). Heterogeneity (I(2)) between countries' proportions in ESBL was significantly high (96.95 % and p < 0.001). The frequently detected genes encoding ESBL were CTX-M, TEM, SHV and OXA while the most infrequent reported genes were KPC and NDM. CONCLUSION: The available studies show a very wide variation in resistance due to ESBL between countries. This highlights a need for active surveillance systems which can help understand the actual epidemiology of ESBL, aid in formulating national or regional guidelines for proper screening of ESBL, and support developing standardized approaches for managing patients colonized with ESBL. PMID- 27186370 TI - Protocol of the Belgian food consumption survey 2014: objectives, design and methods. AB - BACKGROUND: Dietary patterns are one of the major determinants as far as health and burden of disease is concerned. Food consumption data are essential to evaluate and develop nutrition and food safety policies. The last national food consumption survey in Belgium took place in 2004 among the Belgian population aged 15 years and older. Since dietary habits are prone to change over time a new Belgian National Food Consumption Survey (BNFCS2014) was conducted in 2014-2015. METHODS: The BNFCS2014 is a cross-sectional study. A representative sample (n = 3200) of the Belgian population aged 3 to 64 years old was randomly selected from the National Population Register following a multistage stratified sampling procedure. Data collection was divided equally over the four seasons and days of the week in order to incorporate seasonal effects and day-to-day variation in food intake. Information on food intake was collected in adults with two non consecutive 24-h dietary recalls (using the GloboDiet(r) software). In children food intake was collected with two non-consecutive one-day food diaries followed by a completion interview with GloboDiet. Additional data on socio-demographic characteristics, eating habits, lifestyle, food safety (at household level), physical activity and sedentary behaviour were collected with a face-to-face questionnaire using a computer-assisted personal interviewing technique. In the time between the two visits, participants were asked to complete a self administered food frequency questionnaire and health questionnaire. Height, weight and waist circumference were measured. In addition, children and adolescents were asked to wear an accelerometer and keep a logbook for seven consecutive days to objectively measure physical activity and sedentary behaviour. CONCLUSION: The main objective of the BNFCS2014 is to evaluate the habitual food, energy and nutrient intake in the Belgian population and to compare these with recommendations from the national dietary guidelines. A second objective is to monitor eating habits and food safety aspects of the food consumption in Belgium. The results of this dietary monitoring survey, together with the information on the level of physical activity, may underpin future nutrition, food safety and physical activity policies at national and European level. PMID- 27186371 TI - Effectiveness, safety and tolerability of a complex homeopathic medicinal product in the prevention of recurrent acute upper respiratory tract infections in children: a multicenter, open, comparative, randomized, controlled clinical trial. AB - BACKGROUND: The present study was initiated to investigate the effectiveness, safety and tolerability of complex homeopathic CalSuli-4-02 tablets on prevention of recurrent acute upper respiratory tract infections (URTIs) in children, in comparison to another complex homeopathic product. METHODS: The study was designed as a prospective, multicenter, randomized, open, clinical trial with two parallel treatment groups at four outpatient pediatric clinics in Russia. Children aged <= 6 years with susceptibility to acute URTIs (>= three occasions during the last 6 months) were randomized to receive either CalSuli-4-02 or a comparator homeopathic product (control group) for 3 weeks. Primary outcome was the frequency of acute URTIs after 3 and 6 months post-treatment follow-up. Secondary endpoints were changes in complaints and symptoms (total and individual scores), treatment satisfaction, antibiotic use, safety and tolerability. RESULTS: The intention-to-treat analysis involved 200 children (CalSuli-4-02: N = 99, CONTROL: N = 101). In both treatment groups, the median number of acute URTIs was one for 3 months and two, respectively, for the full 6 months post-treatment (Relative Risk: 0.86 (95 %-CI: 0.72-1.03), p = 0.1099). Seasons had no influence on the outcome. At the end of study, CalSuli-4-02 had overall higher odds of getting lower complaints severity total score (Odds ratio: 1.99 (95 %-CI: 1.31 3.02), p = 0.0012) and showing symptom improvement (Odds ratio: 1.93 (95 %-CI: 1.25-3.00), p = 0.0033). Specifically, the complaint "appetite disorder" and the symptom "child's activities" significantly improved more in the CalSuli-4-02 group (p = 0.0135 and p = 0.0063, respectively). Antibiotic use was decreased in both treatment groups at the study end. Overall assessment for satisfaction with and tolerability of treatment was higher with CalSuli-4-02. A low number of non serious adverse drug reactions was reported (CalSuli-4-02: N = 4, CONTROL: N = 1). CONCLUSIONS: Both complex homeopathic products led to a comparable reduction of URTIs. In the CalSuli-4-02 group, significantly less URTI-related complaints and symptoms and higher treatment satisfaction and tolerability were detected. The observation that the use of antibiotics was reduced upon treatment with the complex homeopathic medications, without the occurrence of complications, is interesting and warrants further investigations on the potential of CalSuli-4-02 as an antibiotic sparing option. CLINICAL TRIAL REGISTRATION NUMBER: Roszdravnadzor: Study No 164-563. PMID- 27186372 TI - Do female dieters have an "eating disorder" self-schema? AB - BACKGROUND: The processing of schema-related information is important in the maintenance of specific eating disorder (ED)-related belief systems and psychopathology. To date, most research on differences in the processing of ED schematic information has used interview or self-report questionnaire measures. Dieting is a known risk factor for EDs and dieters have been included in some studies. However, they have not been compared with non-dieters on a novel, objective measure of ED related schema processing. METHODS: The current study recruited healthy female volunteers from the community and divided them into dieting (n = 25) and non-dieting (n = 24) groups using rigorous criteria. ED self schemas with content unrelated to eating, weight and shape were measured using a self-schema processing task. RESULTS: Dieters endorsed significantly more ED relevant words compared to non-dieters, whereas non-dieters rejected significantly more ED relevant words compared to dieters. Reaction times to endorsements and rejections were non-significant when the two groups were compared. In a surprise recall task, dieters recalled significantly more ED relevant words. CONCLUSION: The results of this study support the presence of ED self-schemas with negative content unrelated to eating, weight and shape in otherwise healthy dieters. Implications for future research and the early identification of individuals vulnerable to EDs are discussed. PMID- 27186373 TI - Erratum to: Orthorexia nervosa and self-attitudinal aspects of body image in female and male university students. AB - [This corrects the article DOI: 10.1186/s40337-015-0038-2.]. PMID- 27186374 TI - Expression of IFITM1 as a prognostic biomarker in resected gastric and esophageal adenocarcinoma. AB - BACKGROUND: There is an increasing amount of reports on IFITM1 (interferon inducible transmembrane protein 1) in various malignancies. The aim of this study was to examine the expression of IFITM1 and its prognostic significance in gastroesophageal adenocarcinoma. METHODS: Tissue samples were obtained from a consecutive cohort of 174 patients surgically treated between 2006 and 2010 for gastroesophageal (gastric, gastroesophageal junction and esophageal) adenocarcinoma, not subjected to neoadjuvant therapy. Expression of IFITM1 was examined using immunohistochemistry on tissue microarrays of primary tumors and paired samples of adjacent normal epithelium, intestinal metaplasia and lymph node metastases. RESULTS: Expression of IFITM1 was significantly elevated in primary tumors and lymph node metastases compared to adjacent normal epithelium and intestinal metaplasia, regardless of tumor location. Overexpression of IFITM1 was associated with M0-disease (no distant metastases). In gastric cancer IFITM1 expression was significantly associated with improved TTR (time to recurrence) in Kaplan-Meier analysis and Cox regression, both in the unadjusted analysis (HR 0.33, 95 % CI 0.12-0.88) and in the adjusted analysis (HR 0.32, 95 % CI 0.12 0.87) but there was no significant impact on OS (overall survival). In esophageal adenocarcinoma expression of IFITM1 had no impact on TTR or OS in Kaplan-Meier analyses, but in the adjusted Cox regression IFITM1 expression had a negative impact on both TTR (HR 3.05, 95 % CI 1.09-8.53) and OS (HR 2.71, 95 % CI 1.11 6.67). CONCLUSIONS: IFITM1 was overexpressed in gastroesophageal adenocarcinoma and associated with M0-disease. In gastric cancer IFITM1 expression had a positive impact on TTR but in esophageal cancer it seemed to have an adverse impact on survival. The reason for the diverging prognostic impact of IFITM1 in esophageal and gastric cancer is unclear and warrants further studies. PMID- 27186375 TI - Land or sea? Foraging area choice during breeding by an omnivorous gull. AB - BACKGROUND: Generalist predators may vary their diet and use of habitat according to both internal state (e.g. breeding stage) and external (e.g. weather) factors. Lesser black-backed gulls Larus fuscus (Linnaeus 1758) are dietary generalists, foraging in both terrestrial and marine habitats during breeding. We investigate what affects the gulls' propensity to forage at sea or on land. We assess the importance of terrestrial foraging to gulls in the Baltic Sea (sub. sp. L. f. fuscus), looking especially at their use of agricultural fields. RESULTS: Through the GPS tracking of 19 individuals across 3 years we tracked 1038 foraging trips and found that 21.2 % of foraging trips were predominantly terrestrial, 9.0 % were a mix of terrestrial and marine, and 68.5 % were exclusively marine. Terrestrial trips were (1) more frequent when departing around sunrise, whereas marine trips occurred throughout the day. Additionally, trips with mostly land based foraging decreased as the breeding season progressed, suggesting dietary switching coincident with the onset of chick provisioning. (2) During cloudy and cold conditions terrestrial foraging trips were more likely. (3) We found no differences between sexes in their land-based foraging strategy. (4) Gull individuals showed great variation in foraging strategy. Using observations of agricultural fields, carried out for one year, we found that (5) gulls preferentially foraged on fields with short vegetation, and there was a positive association with occurrence of waders and other species of gulls. (6) The availability and use of these preferred fields decreased through the breeding period. CONCLUSIONS: This study found high prevalence of terrestrial foraging during early breeding as well as support for dietary switching early in the breeding season. The overall tendency for marine or terrestrial foraging was consistent within individuals, with gull identity accounting for much of the variation observed in foraging trips. Our results suggest that anthropogenic terrestrial food sources may play a role in the low breeding success of these gulls through either variation in quantity and/or quality. Finally, our study demonstrates the potential of combining data from GPS-tracking of individual animals with the 'ground-truthing' of habitat visited to elucidate the otherwise nebulous behavior of a generalist predator. PMID- 27186376 TI - Diagnosis of perinuclear anti-neutrophil cytoplasmic antibody-associated microscopic polyangiitis in silicotics: case report. AB - BACKGROUND: An association between silica exposure and autoimmune diseases including rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus, and anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis has been made. CASE PRESENTATION: A 56-year-old male presented with silicosis and had an occupational history of precious metal processing for 30 years and a 30 pack year smoking history. The patient was diagnosed with pneumoconiosis and received compensation. No other complications were reported for pneumoconiosis. The patient suddenly presented with a non-specific headache for several days and microscopic hematuria was identified upon examination in the outpatient clinic. Following several weeks, the patient presented with aggravated dyspnea and hemoptysis, and his Modification of Diet in Renal Disease estimated glomerular filtration rate indicated acute kidney injury. Diagnostic analysis revealed perinuclear ANCA-associated microscopic polyangiitis (p-ANCA-associated MPA). CONCLUSION: Exposure to silica dust was likely one of the cause of p-ANCA associated MPA. Possible pathogenic mechanisms of autoimmune diseases in silicotics and emphasis of the necessity for early diagnosis are discussed. PMID- 27186377 TI - Erratum to: Impact of an integrated obesity management system on patient's care - research protocol. AB - [This corrects the article DOI: 10.1186/s40608-014-0019-z.]. PMID- 27186378 TI - Fatal cardiovascular instability secondary to hypercalcaemia and intracellular calcium deposition complicating T-cell leukaemia-lymphoma. AB - Adult T-cell leukaemia-lymphoma is a rare haematological malignancy, which can cause severe hypercalcaemia and metastatic calcification resulting in life threatening arrhythmias. PMID- 27186379 TI - Rare times rare: The hyponatremia, rhabdomyolysis, anterior compartment syndrome sequence. AB - Primary polydipsia occurs in up to 25% of patients with chronic psychiatric disorders (especially schizophrenia), related to the disease, its treatment or both. Urine output fails to match intake >10 L/day and water intoxication may develop. Rhabdomyolysis is a rare complication of hyponatremia, and an acute anterior compartment syndrome of the leg, an emergency, may be very rarely associated. PMID- 27186380 TI - Intoxication with alcohol: An underestimated trigger of Brugada syndrome? AB - Alcohol intoxication is a potentially under-recognised precipitant of Brugada syndrome. Higher pre-cordial electrocardiogram lead placement increases sensitivity of detecting the Brugada pattern. PMID- 27186381 TI - Rare and unusual clinicopathologic presentation of renal AL amyloidosis. AB - Rarely, renal light chain (AL) amyloidosis may present without significant proteinuria owing to glomerular sparing and amyloid deposition confined to the vasculature and tubulointerstitium. PMID- 27186382 TI - Care Instability in Nursing Homes; A Qualitative Study. AB - BACKGROUND: The use of long-term care services has risen and this trend is expected to continue as the population reaches old age. OBJECTIVES: This study was performed to assess the caring conditions in nursing homes. PATIENTS AND METHODS: This study was conducted with a qualitative approach using conventional qualitative content analysis. The study was conducted on 23 Iranian participants including 14 elders and 9 caregivers. Data was collected with unstructured interviews and continued to the point of data saturation. Analysis of data was performed continually and concurrently with data collection through a comparative method. RESULTS: Three themes emerged from 595 open codes including care as unpleasant task, sustained care and insufficient resources. Ten subthemes indicated participants' experiences and understanding of caring conditions in a nursing home. CONCLUSIONS: The prevailing given care was the routine one with a focus on physical aspects, although there was some psychological care given to the older people. The findings of this research are guidelines for managers and care planners in nursing homes who should pay attention to physical and psychological care needs of older people. In addition, it is important to pay close attention to the needs of caregivers and provision of instructions for treatment, supervision and education of caregivers and medical students to provide a better care. PMID- 27186383 TI - Health Information Management System for Elderly Health Sector: A Qualitative Study in Iran. AB - BACKGROUND: There are increasing change and development of information in healthcare systems. Given the increase in aging population, managers are in need of true and timely information when making decision. OBJECTIVES: The aim of this study was to investigate the current status of the health information management system for the elderly health sector in Iran. MATERIALS AND METHODS: This qualitative study was conducted in two steps. In the first step, required documents for administrative managers were collected using the data gathering form and observed and reviewed by the researcher. In the second step, using an interview guide, the required information was gathered through interviewing experts and faculty members. The convenience, purposeful and snowball sampling methods were applied to select interviewees and the sampling continued until reaching the data saturation point. Finally, notes and interviews were transcribed and content analysis was used to analyze them. RESULTS: The results of the study showed that there was a health information management system for the elderly health sector in Iran. However, in all primary health care centers the documentation of data was done manually; the data flow was not automated; and the analysis and reporting of data are also manually. Eventually, decision makers are provided with delayed information. CONCLUSIONS: It is suggested that the steward of health in Iran, the ministry of health, develops an appropriate infrastructure and finally puts a high priority on the implementation of the health information management system for elderly health sector in Iran. PMID- 27186384 TI - Population-Based Preference Weights for the EQ-5D Health States Using the Visual Analogue Scale (VAS) in Iran. AB - BACKGROUND: Health-related quality of life (HRQoL) is used as a measure to valuate healthcare interventions and guide policy making. The EuroQol EQ-5D is a widely used generic preference-based instrument to measure Health-related quality of life. OBJECTIVES: The objective of this study was to develop a value set of the EQ-5D health states for an Iranian population. PATIENTS AND METHODS: This study is a cross-sectional study of Iranian populations. Our sample from Iranian populations consists out of 869 participants, who were selected for this study using a stratified probability sampling method. The sample was taken from individuals living in the city of Tehran and was stratified by age and gender from July to November 2013. Respondents valued 13 health states using the visual analogue scale (VAS) of the EQ-5D. Several fixed effects regression models were tested to predict the full set of health states. We selected the final model based on the logical consistency of the estimates, the sign and magnitude of the regression coefficients, goodness of fit, and parsimony. We also compared predicted values with a value set from similar studies in the UK and other countries. RESULTS: Our results show that the HRQoL does not vary among socioeconomic groups. Models at the individual level resulted in an additive model with all coefficients being statistically significant, R(2) = 0.55, a value of 0.75 for the best health state (11112), and a value of -0.074 for the worst health state (33333). The value set obtained for the study sample remarkably differs from those elicited in developed countries. CONCLUSIONS: This study is the first estimate for the EQ-5D value set based on the VAS in Iran. Given the importance of locally adapted value set the use of this value set can be recommended for future studies in Iran and In the EMRO regions. PMID- 27186385 TI - The Most Common Herbs to Cure the Most Common Oral Disease: Stomatitis Recurrent Aphthous Ulcer (RAU). AB - CONTEXT: Recurrent aphthous ulcer (RAU) is an oral disease and the most common oral lesion, with 2% to 66% of the world's population infected annually. Its prevalence is about 25% in Tehran and 27.6% in Mashhad. The etiology of RAU is multifactorial. Aphthous risk factors include: immunological factors, psychological factors, stress, trauma, sensitivity, family history, blood disorders, malnutrition, and use of certain medications, It should be noted that the best treatment for RAU is the topical application of drugs. The use of topical treatments is recommended not only because the drug can directly impact the source of the disease, but also systemic side effects of the drug are reduced. Treatment of RAU has been considered in Iranian traditional medicine (ITM), and is covered in therapeutic books. The use of herbs in RAU has a centuries-old history; accordingly, extensive research should be conducted for this treatment of the disease. EVIDENCE ACQUISITION: Iranian medical sources were reviewed and effective plants used in the traditional treatment of RAU were found and compared with new findings. Finally, we have created a table listing the plants that are part of the therapeutic protocol for RAU. RESULTS: Based on this article we can explain some of traditional pharmacological effects of plants and how these plants can be a source for a cure. CONCLUSIONS: The plants listed can be used as a prediction of RAU management. Of course, there are is no evidence for curing RAU by some of these plants in allopathic medicine, and the further investigations in this area could lead to the discovery of a new drug. PMID- 27186386 TI - Turbulent Atmosphere-Based Dominant Management Behavior of the Head Nurses in Clinical Wards: A Qualitative Study. AB - BACKGROUND: Nursing management is the most important aspect for providing high quality nursing care. Therefore, skillful nursing managers, such as head nurses, are required to accomplish this goal. High-quality nursing care is one of the most important principles of health organizations to ensure society's health. OBJECTIVES: The goal of the conventional content analysis is to explain the dominant experienced-based behavior of the head nurses in clinical wards. MATERIALS AND METHODS: This study was conducted by applying a quality study approach with a common content analysis model (Granheim and Lundmen). The participants were 25 head nurses who were working in the wards of various hospitals in Zahedan City. They were selected via the purposeful sampling method. The data were collected thoroughly and continued until a saturation stage was reached. RESULTS: The result of data analysis was the theme "turbulent atmosphere based management," which consists of five categories as follows: the work culture of the ward, job burnout, negligent evaluation, job conflict, and decision making with limited effects. CONCLUSIONS: The analysis of the findings of the present study through considering the defined categories demonstrated that, to modify and correct the turbulent atmosphere-based management, several important measures are required and need to be continually monitored. PMID- 27186387 TI - A Proper Enteral Nutrition Support Improves Sequential Organ Failure Score and Decreases Length of Stay in Hospital in Burned Patients. AB - BACKGROUND: Severe burned patients developed metabolic imbalances and systemic inflammatory response syndrome (SIRS), which can lead to malnutrition, impaired immunologic response, multiple organ failure and death. Studies have shown that providing an early and adequate nutrition support can lower hypermetabolic response and improve the outcome. Unfortunately, little emphasis has been given to the role of nutritional support, especially for demonstrating the importance of a proper nutritional support in determining the outcome of critically burned patients. OBJECTIVES: This study was designed to determine the possible protective effect of early and adequate nutrition support on sequential organ failure assessment (SOFA) score and length of stay (LOS) in hospital, in thermal burn victims. PATIENTS AND METHODS: Thirty patients with severe thermal burn (More than 20% of total body surface area [TBSA] burn), on the first day in the intensive care unit, joined this double-blinded randomized controlled clinical trial. Patients were randomly divided into two groups: control group (group C, 15 patients) received hospital routine diet (liquid and chow diet, ad libitum) while intervention group (group I, 15 patients) received commercially prepared solution, with oral or tube feeding. The caloric requirement for these patients was calculated, according to the Harris-Benedict formula. The SOFA score was also measured on admission (SOFA0), day 2 (SOFA1), day 5 (SOFA2) and day 9 (SOFA3), consequently. The difference between the last measurement (SOFA3) and day 2 (SOFA1) was calculated. RESULTS: The results showed that there was a significant change between SOFA3 and SOFA1, {-1[(-1) - 0], P = 0.013 vs. -1 [(-2) - 0], P = 0.109}. Mean LOS in hospital, for patients consuming commercial standard food, also proved to be shorter than those consuming hospital routine foods (17.64 +/- 8.2 vs. 23.07 +/- 11.89). CONCLUSIONS: This study shows that an adequate nutritional support, in patients with severe burn injury, can improve SOFA score. It is also more cost-effective, resulting in a shorter LOS in hospital. PMID- 27186388 TI - Distal Femur Morphology of Iranian Population and Correlation With Current Prostheses. AB - BACKGROUND: Maintaining proper size and rotation of components of total knee arthroplasty is mandatory for optimal longevity. Ethnical differences may affect the fitness of prostheses that were manufactured mainly based on Caucasian dimensions. OBJECTIVES: To evaluate the distal femur morphology of the Iranian population at the level of standard cuts simulated via computed tomography. PATIENTS AND METHODS: During 2013, 150 consecutive patients (96 males and 54 females) from the outpatient Department of Orthopedic Surgery of Rasoul Akram Hospital with knee CT scans were studied. We entered cases with apparent normal extremity alignment and bone maturity. Exclusion criteria were history of fracture or conditions affecting knee profile. Standard cuts were simulated on the CT scan using the Marco Pacs program. For each bone, anteroposterior (AP), mediolateral (ML), and aspect ratio (ML/AP) were measured. Values were compared with the sizing of four currently available prostheses. RESULTS: The mean age of the patients was 43 years (range: 17 to 80). All isolated parameters were higher in men significantly (P < 0.001). However, the aspect ratio did not show any significant difference (1.51 +/- 0.11 vs 1.46 +/- 0.1), suggestive of a similar configuration of distal femur profiles between genders. Ultimately, close correlations were observed among simulated cuts and size-matched femoral components of the prostheses. For females, however, components were mostly overhang mediolaterally except for one gender-specific subset. Decrement in the aspect ratio for larger knees was another mismatch with current prostheses that preserve an almost constant ratio throughout all sizes. CONCLUSIONS: Our findings may be applied by manufacturers to design prostheses more compatible with Asian populations. Alterations to the shape of components should be considered to provide optimal coverage. PMID- 27186389 TI - An Evidence-Based Review on Medicinal Plants Used as Insecticide and Insect Repellent in Traditional Iranian Medicine. AB - CONTEXT: Insects can be the cause of major ecological problems; they can transmit microbes and parasites that affect humans, and damage food crops, trees, and homes. The total economic cost of insect-related damage and disease is immeasurable. In traditional Iranian medicine (TIM), several medicinal plants have been identified as insecticides or insect repellents, but many of them are still unknown. Therefore, the aim of this study was to review the insecticidal or insect repellent activity of certain medicinal plants described in TIM. EVIDENCE ACQUISITION: Information about medicinal plants proposed as insecticides and insect repellents in the TIM was collected from the TIM literature, and searched in modern medical databases to find studies that confirmed their efficacy. RESULTS: Modern investigations have supported the claims of the insecticidal activity of several plants, including Allium sativum, Artemisia absinthium, Citrullus colocynthis, Laurus nobilis, Mentha pulegium, Myrtus communis, Nerium oleander, Ocimum basilicum, and Origanum majorana. However, in the cases of plants like Iris florentina and Malva sylvestris, there is not enough evidence in modern medicine to prove their effectiveness with regard to their insecticidal and insect repellent activities. CONCLUSIONS: This study confirmed the Iranian traditional medicine claims of the insecticidal and insect repellent activity of certain plants. Further pharmacological and clinical studies are recommended to evaluate the overall efficacy and possible mechanisms underlying these herbs. PMID- 27186390 TI - Evaluation of Association of ADRA2A rs553668 and ACE I/D Gene Polymorphisms with Obesity Traits in the Setapak Population, Malaysia. AB - BACKGROUND: alpha-adrenergic receptor 2A (ADRA2A) and angiotensin-converting enzyme (ACE) genes have been variably associated with obesity and its related phenotypes in different populations worldwide. OBJECTIVES: This cross-sectional study aims to investigate the association of adrenergic receptor alpha2A (ADRA2A) rs553668 and angiotensin-converting enzyme (ACE) I/D single nucleotide polymorphisms (SNPs) with obesity traits (body mass index-BMI; waist-hip ratio WHR; total body fat percentage - TBF) in a Malaysian population. MATERIALS AND METHODS: Demographic and clinical variables were initially collected from 230 subjects via convenience sampling among residents and workers in Setapak, Malaysia, but in the end only 214 multi-ethnic Malaysians (99 males; 45 Malays, 116 ethnic Chinese, and 53 ethnic Indians) were available for statistical analysis. Genotyping was performed by polymerase chain reaction using DNA extracted from mouthwash samples. RESULTS: The overall minor allele frequencies (MAFs) for ADRA2A rs553668 and ACE I/D were 0.55 and 0.56, respectively. Allele distribution of ACE I/D was significantly associated with ethnicity and WHR class. Logistic regression analysis showed that subjects with the ACE II genotype and I allele were, respectively, 2.15 and 1.55 times more likely to be centrally obese, but when adjusted for age and ethnicity, this association was abolished. Covariate analysis controlling for age, gender, and ethnicity also showed similar results, where subjects carrying the II genotype or I allele did not have significantly higher WHR. Combinatory genotype and allele analysis for ADRA2A rs553668 and ACE I/D showed that subjects with both ADRA2A rs553668 GG and ACE I/D II genotypes had significant lowest WHR compared to other genotype combinations. CONCLUSIONS: The ACE II genotype might be a protective factor against central adiposity risk among the Malaysian population when in combination with the ADRA2A rs553668 GG genotype. PMID- 27186391 TI - MicroRNA-338-3p suppresses metastasis of lung cancer cells by targeting the EMT regulator Sox4. AB - Metastasis remains the leading cause of the majority of cancer-related mortality. MicroRNAs (miRNAs) have frequently emerged as tumor metastatic regulator by acting on multiple signaling pathways. In the present study, we demonstrated that miR-338-3p was significantly downregulated in highly metastatic NSCLC cell lines and clinical metastatic tissues. Then, we found that introduction of miR-338-3p significantly suppressed the migration and invasion of lung cancer cells both in vitro and in vivo, suggesting that miR-338-3p may be a novel tumor suppressor. Further studies indicated that the EMT-related transcription factor Sox4 was one direct target gene of miR-338-3p, evidenced by the direct binding of miR-338-3p with the 3'untranslated region (3'UTR) of Sox4. Furthermore, miR-338-3p could decrease the expression of Sox4 both at mRNA and protein levels. Notably, the EMT marker E-cadherin or vimentin, a downstream regulator of Sox4, was also down regulated or up-regulated upon miR-338-3p treatment. Additionally, over expressing or silencing Sox4 could elevate or inhibit the migration and invasion of lung cancer cells, parallel to the effect of miR-338-3p on the lung cancer cells. Meanwhile, knockdown of Sox4 reversed the enhanced migration and invasion mediated by miR-338-3p. These results indicated that miR-338-3p suppressed the migration and invasion of NSCLC cells through targeting Sox4 involving in the EMT process. Thus, our finding provides new insight into the mechanism of NSCLC progression. Therapeutically, miR-338-3p may serve as a potential target in the treatment of human lung cancer. PMID- 27186392 TI - MicroRNA-10b regulates epithelial-mesenchymal transition by modulating KLF4/Notch1/E-cadherin in cisplatin-resistant nasopharyngeal carcinoma cells. AB - Epithelial-mesenchymal transition (EMT) is an initiating event in tumor cell invasion and metastasis that contributes to therapeutic resistance to compounds including cisplatin. MicroRNAs (miRNAs) have been associated with EMT as well as resistance to standard therapies. However, the underlying mechanisms by which miRNAs control the development of resistance to cisplatin (DDP), and the accompanying EMT-like properties are required to elucidate. Here we show that microRNA-10b (miR-10b) is up-regulated in HNE1/DDP cells, and inhibition of miR 10b expression reversed the EMT phenotype. However, over-expression of miR-10b was able to promote the acquisition of an EMT phenotype in HNE1 cells. Additionally, we identified that miR-10b expression inversely correlates with KLF4, which then controls expression of Notch1. Knock-down of Notch1 inhibited cell migration, invasion, and reversed EMT in HNE1/DDP cells, which was dependent on miR-10b. In summary, our results reveal that miR-10b regulates EMT by modulating KLF4/Notch1/E-cadherin expression, which promotes invasion and migration of nasal pharyngeal carcinoma cells. PMID- 27186393 TI - Anti-CD40 antibody and toll-like receptor 3 ligand restore dendritic cell mediated anti-tumor immunity suppressed by morphine. AB - The influence of morphine on host immunity and the underlying mechanism are still unclear. In the current study, we investigated the influence of morphine on dendritic cells (DCs), its possible mechanism of action, and the molecules that could reverse these effects. Morphine suppressed DC maturation, antigen presenting abilities, and the ability to activate antigen-specific CD8(+) T cells. Morphine-treated DCs also secreted higher concentrations of IL-10, but lower IL-6 and TNF-alpha. Morphine-treated DCs showed decreased ERK1/2 phosphorylation and reduced p38 dephosphorylation. The in vivo administration of immuno-modulators, anti-CD40 Ab and TLR3 ligand-poly(I:C), enhanced antigen specific immunity, promoted the anti-tumor effects, and prolonged the survival of morphine-treated, tumor-bearing mice by promoting the maturation and function of BMM-derived DCs by enhancing ERK1/2 phosphorylation and p38 dephosphorylation. We concluded that morphine can inhibit DC-mediated anti-tumor immunity by suppressing DC maturation and function. Immuno-modulators, such as anti-CD40 Abs and TLR agonists, can restore the DC-mediated anti-tumor immunity. Use of immuno modulators could serve as a useful approach to overcome the immunocompromised state generated by morphine. PMID- 27186394 TI - MiR-326 regulates cell proliferation and migration in lung cancer by targeting phox2a and is regulated by HOTAIR. AB - Recent findings indicate that microRNAs (miRNAs) play a crucial role in lung cancer development, progression and regression. In our previous study, we identified miR-326 is down-regulated in lung cancer. However, the role of miR-326 hasn't been revealed yet. The aim of the current study is to investigate the function and regulation mechanism of miR-326 in lung cancer. MTT assays, Transwell migration assays and xenograft model in nude mice were carried to detect the effects of miR-326 on cell proliferation, migration and tumor growth in nude mice. Flow cytometry was used to analyze the effects of miR-326 on cell cycle and apoptosis. By using siRNAs and luciferase assays, we also demonstrated that Phox2a is a functional target of miR-326, and that miR-326 is regulated by long non-coding RNA HOTAIR through silencing HOTAIR. Enforced expression of miR 326 inhibited cell proliferation and migration in vitro and tumor growth in nude mice, decreased proportion of cells in S phase and increased cell apoptosis in both A549 and H838 cells. In addition, we found miR-326 bound to 3'UTR of Phox2a but not KLF3, and enforced expression of miR-326 decreased accumulation of Phox2a in both A549 and H838. Moreover, exogenous expression of Phox2a compromised inhibitory effects of miR-326 on cell proliferation and migration. We also found silencing of HOTAIR caused increased expression of miR-326. miR-326 regulates cell proliferation and migration in lung cancer by targeting Phox2a and is regulated by HOTAIR. PMID- 27186395 TI - Methyl jasmonate induces apoptosis and pro-apoptotic autophagy via the ROS pathway in human non-small cell lung cancer. AB - Methyl jasmonate (MJ) is a botanical hormone that serves as a signal transduction intermediate and regulates cell death in stressed plants. MJ induces cell cycle arrest, apoptosis and non-apoptotic cell death selectively in cancer cells. However, the underlying mechanism of MJ-induced apoptosis remains unclear. In this study, we examined the molecular mechanism through which MJ induces apoptosis in human non-small cell lung cancer (NSCLC). We found that MJ triggered apoptosis via the DDIT3-TNFRSF10B-CASP axis. MJ treatment significantly decreased the expression of CFLAR (CASP8 and FADD-like apoptosis regulator, an inhibitor of CASP8) in NSCLC cells, and ectopic expression of CFLAR partly protected cells from MJ-induced apoptosis. MJ also induced pro-apoptotic autophagy in NSCLC cells. Importantly, inhibition of ROS suppressed both MJ-induced apoptosis and autophagy. Taken together, MJ induces apoptosis and pro-apoptotic autophagy in NSCLC cells through the ROS pathway. Thus, MJ and its derivative treatment may serve as a novel chemotherapeutic strategy for cancer therapy. PMID- 27186396 TI - Cancer-associated fibroblasts promote endometrial cancer growth via activation of interleukin-6/STAT-3/c-Myc pathway. AB - Cancer-associated fibroblasts (CAFs) secrete various pro-tumorigenic cytokines, yet the role of these cytokines in the progression of endometrial cancer remains unclear. We found that CAFs isolated from human endometrial cancer (EC) tissues secreted high levels of interleukin-6 (IL-6), which promotes EC cell proliferation in vitro. Neutralizing IL-6 in CAF-conditioned media reduced (47% inhibition) while IL-6 recombinant protein increased cell proliferation (~2.4 fold) of both EC cell lines and primary cultures. IL-6 receptors (IL-6R and gp130) were expressed only in EC epithelial cells but not in CAF, indicating a one-way paracrine signaling. In the presence of CAF-conditioned media, Janus kinase/signal transducers and activators of transcription (JAK/STAT3) pathway was activated in EC cells. Treatment with JAK and STAT3 specific inhibitors, AD412 and STATTIC, respectively, significantly abrogated CAF-mediated cell proliferation, indicating the role of IL-6 activation in EC cell proliferation. We further showed that one of STAT-3 target genes, c-Myc, was highly induced in EC cells after exposure to CAF-conditioned medium at both mRNA (>105-fold vs. control) and protein level (>2-fold vs. control). EC cell proliferation was dependent on c-Myc expression, as RNAi-mediated c-Myc down-regulation led to a significant 46% reduction in cell viability when compared with scrambled control. Interestingly, CAF-conditioned media failed to promote proliferation in EC cells with reduced c-Myc expression, suggesting that CAF-mediated cell proliferation was also dependent on c-Myc expression. Subcutaneous tumor xenograft model showed that EC cells grew at least 1.4 times larger when co-injected with CAF, when compared to those injected with EC cells alone. Mice injected with EC cells with down-regulated c-Myc expression, however, showed at least 2.5 times smaller tumor compared to those in control group. Notably, there was no increase of tumor size when co-injected with CAFs. Further immunohistochemical staining on human tissues showed positive expression of IL-6 receptors, phosphorylated-STAT3 and c-Myc in human EC tissues with less signals in benign endometrium. Taken together, our data suggests that IL-6 secreted by CAF induces c-Myc expression to promote EC proliferation in vitro and in vivo. IL-6 pathway can be a potential target to disrupt tumor-stroma interaction in endometrial cancer progression. PMID- 27186397 TI - A placental growth factor-positively charged peptide potentiates the antitumor activity of interferon-gamma in human brain glioblastoma U87 cells. AB - Interferons have been marketed to treat hematological malignancies, but their efficacy in the treatment of solid tumors has been significantly hindered by low antitumor efficacy and numerous side effects. We used a "cDNA in-frame fragment" library screening method to identify short cDNA peptides that potentiate the anti tumor activity of interferons. In this study, we synthesized a hybrid molecule by fusing a short positively charged peptide derived from placental growth factor-2 to the C-terminus of human IFNgamma. Using the human brain glioblastoma U87 cell line as a model system, we found that the hybrid interferon exhibited significantly higher activity than did the wild-type IFNgamma in inhibiting tumor cell growth. As compared with the unmodified IFNgamma, the hybrid interferon was better at inhibiting cell invasion in a matri-gel assay and at decreasing tumor colony formation. The enhanced antitumor activity of the synthetic interferon was correlated with the activation of interferon pathway genes and the blockade of tumor cell division at the S-G2/M phase. This study demonstrates the potential of a synthetic IFNgamma for use as a novel antitumor agent. PMID- 27186398 TI - Guggulsterone-induced apoptosis in cholangiocarcinoma cells through ROS/JNK signaling pathway. AB - Cholangiocarcinoma (CCA), the most common biliary tract malignancy, is arising from the bile duct epithelium with the global significantly increased morbidity and mortality. Here, we showed the effect of guggulsterone, a steroid found in the resin of the guggul plant, on human HuCC-T1 and RBE CCA cells. Exposure to various concentrations of guggulsterone for multiple action time resulted in significant apoptosis in the CCA cells via activating both extrinsic and intrinsic pathways. Furthermore, we demonstrated that the apoptosis of CCA cells was induced by Reactive oxygen species (ROS) mediated JNK signaling pathway. Consistently, inhibition of JNK activity, overexpression of JBD, its binding protein or reduction of ROS by overexpression of catalase, all decreased apoptotic cells. Our results also revealed that guggulsterone-induced apoptosis was coupled with endoplasmic reticulum stress (ERS) in CHOP-dependent pathway. Downregulation of CHOP instead of other ERS markers could inhibit CCA cell apoptosis. Taken together, our results showed that guggulsterone could induce apoptosis of human CCA cells through ROS/JNK signaling pathway, indicating that guggulsterone could be important for the clinical therapy of CCA. PMID- 27186399 TI - Androgen receptor expands the population of cancer stem cells in upper urinary tract urothelial cell carcinoma cells. AB - Androgen receptor (AR) affects the development and progression of upper urinary tract urothelial cell carcinoma (UUTUC). However, the regulatory mechanism exerted by AR to affect UUTUC cells remains unclear. Here we investigated whether AR promotes UUTUC development and progression, possibly by expanding the population of cancer stem cells (CSCs), which are a particular population of cells within cancer cells responsible for tumor initiation, drug resistance and metastasis. We compared UUTUC cells with or without the addition of AR on their CSC population with flow cytometry, colony formation and sphere formation assay to determine the effect of AR on CSC activity, and real-time PCR was used to detect the expression stemness genes and miRNAs. In vivo tumor formation was evaluated with the implantation of cancer cells in nude mice. We found that the addition of AR in UUTUC cells, significantly increased the population of CSC, clonogenicity, sphere formation and the expression of stemness genes (Oct4, Bmi1 and Nanog), altered CSC-related miRNA profile, as well as promoted epithelial mesenchymal transition (EMT). And AR inhibitor, enzalutamide was shown to suppress AR's effect on tumorsphere formation. Furthermore, in an immune deficient mouse model, the addition of AR in UUTUC cells also increased the tumor formation capacity. This study will help us better understand the extent to which AR contributes to UUTUC progression by expanding their CSC population and capacity. Our findings could explain high incidence of UUTUC observed in males. And targeting AR may lead to novel therapeutic approaches for genetically diversified urothelial carcinomas in precision medicine era. PMID- 27186400 TI - Overexpression and oncogenic function of HMGA2 in endometrial serous carcinogenesis. AB - The high-mobility group A protein 2 (HMGA2) is a non-histone chromatin factor highly expressed in fetal tissue and malignant tumors but rarely detected within normal adult tissues. The clinical implications and biological functions of HMGA2 in endometrial carcinoma are largely unknown. Here we report that HMGA2 expression was barely detected in benign endometrium samples (2 of 28 samples). However, HMGA2 expression increased significantly from precancerous lesion endometrial glandular dysplasia (7 of 17, 41.2%), to serous endometrial intraepithelial carcinoma (5 of 8, 62.5%) and to full blown endometrial serous carcinoma (39 of 59, 66.1%). Functional characterization of HMGA2 revealed that the gene has both tumor growth promotion and metastasis. In addition, HMGA2 induced epithelial-mesenchymal transition (EMT) through modulation vimentin and beta-catenin. Furthermore, HMGA2 overexpression started from endometrial serous precancers, non-invasive cancers, as well as in full blown carcinomas in a p53 knockout mouse model we recently established in our laboratory. Our findings suggest that HMGA2 may serve as a useful diagnostic marker in the assessment of endometrial serous cancer and its precursor lesions. PMID- 27186401 TI - Deregulated miR-296/S100A4 axis promotes tumor invasion by inducing epithelial mesenchymal transition in human ovarian cancer. AB - S100A4 represents an important member of the S100 family of small calcium-binding proteins. Increased expression of S100A4 has been observed in chronic inflammatory and autoimmune diseases, such as idiopathic inflammatory myopathies. The majority of studies of S100A4 are focused on cancer research; however, the oncogenic roles of S100A4 in epithelial ovarian cancer (EOC) remain largely unexplored. In this study, S100A4 expression is significantly up-regulated in ovarian cancer and associated with the clinical stage of EOC patients. Attenuation of S100A4 expression results in decreased cell mobility and metastatic capacity, whereas overexpression of S100A4 enhanced the invasive ability of EOC cells. Then by an integrated informatics analysis and luciferase reporter assay, we identify that miR-296 is a critical upstream regulator of S100A4. In addition, deregulated miR-296/S100A4 axis facilitates epithelial mesenchymal transition (EMT) process as demonstrated by altered expression of EMT related markers. In conclusion, our study reveals that deregulated miR-296/S100A4 promotes tumor progression in EOC, and provides evidence that miR-296/S100A4 axis related signaling may represent a potential target for EOC therapy. PMID- 27186402 TI - SIAH2 protein expression in breast cancer is inversely related with ER status and outcome to tamoxifen therapy. AB - Our previous study demonstrated that high mRNA levels for Seven in Absentia Homolog 2 (SIAH2) correlated with high Estrogen Receptor (ER) mRNA levels and with longer progression-free survival (PFS) after first-line tamoxifen. Others showed high SIAH2 protein levels in ER-negative breast cancer associated with an unfavorable relapse-free survival. In the current study, we investigated SIAH2 protein expression to clarify the discrepancy between protein and mRNA findings and to determine its diagnostic value in breast cancer patients. Tissue microarrays (TMAs) containing core specimens of primary breast tumors were immunohistochemically stained for SIAH2 protein. The TMAs analyzed a cohort of 746 patients with primary breast cancer (PBC) and a cohort of 245 patients with ER-positive metastatic breast cancer (MBC) treated with first-line tamoxifen. SIAH2 staining was scored for intensity and proportion of positive tumor cells and evaluated for its relationship with metastasis-free survival (MFS) and PFS. Multivariate survival analyses included traditional prognostic or predictive factors, respectively. The PBC-cohort had 263 patients with high SIAH2 protein expression and decreased expression of ER protein and mRNA levels (P = 0.005 and P = 0.003, respectively). High SIAH2 levels correlated with significant unfavorable MFS in lymph node negative, ER-positive breast cancer patients. The MBC-cohort had 86 patients with increased SIAH2 protein expression. High SIAH2 expression was associated with an unfavorable PFS after first-line tamoxifen in multivariate analyses (HR = 1.45; 95% CI, 1.07-1.96; P = 0.015). In conclusion, SIAH2 protein expression is especially observed in ER-negative tumors. Its prognostic value in breast cancer does not add to current prognostic markers. The proportion of SIAH2-positive cells can be used as biomarker to predict tamoxifen treatment failure in MBC patients. PMID- 27186403 TI - Long non-coding RNA Linc00152 is a positive prognostic factor for and demonstrates malignant biological behavior in clear cell renal cell carcinoma. AB - Accumulating evidence demonstrates that lncRNAs play important roles in regulating gene expression and are involved in various pathological processes. In the present study, we screened the lncRNAs profile in clear cell renal cell carcinoma (ccRCC) from The Cancer Genome Atlas (TCGA) database, and got linc00152, a differentially expressed lncRNA that haven't been reported in ccRCC. To further explore its role in ccRCC, the level of Linc00152 was detected in 77 paired ccRCC tissues and renal cancer cell lines by qRT-PCR, and its association with overall survival was assessed by statistical analysis. Linc00152 expression was significantly up-regulated in cancerous tissues and cell lines compared with normal counterparts, and high Linc00152 expression was closely associated with advanced TNM stage. Moreover, Linc00152 was found to be able to serve as an independent predictor of overall survival. Further experiments demonstrated that overexpression of Linc00152 can significantly promote cell proliferation and invasion, inhibit cell cycle arrest in G1 phase and dramatically decrease apoptosis in both 786O and Caki-2 cell lines, whereas the opposite results were observed with attenuated Linc00152 expression. Our data suggest that Linc00152 is a novel molecule involved in ccRCC progression as well as a potential prognostic biomarker and therapeutic target. PMID- 27186404 TI - Transient fasting enhances replication of oncolytic herpes simplex virus in glioblastoma. AB - Short-term nutritional restriction (fasting) has been shown to enhance the efficacy of chemotherapy by sensitizing cancer cells and protecting normal cells in a variety of cancer models, including glioblastoma (GBM). Cancer cells, unlike normal cells, respond to fasting by promoting oncogenic signaling and protein synthesis. We hypothesized that fasting would increase the replication of oncolytic herpes simplex virus (oHSV) in GBM. Patient-derived GBM cell lines were fasted by growth in glucose and fetal calf serum restricted culture medium. "Transient fasting", 24-hour fasting followed by 24-hour recovery in complete medium, increased late virus gene expression and G47Delta yields about 2-fold in GBM cells, but not in human astrocytes, and enhanced G47Delta killing of GBM cells. Mechanistically, "transient fasting" suppressed phosphorylation of the subunit of eukaryotic initiation factor 2alpha (eIF2alpha) and c-Jun N-terminal kinases (JNK) in GBM cells, but not in astrocytes. Pharmacological inhibition of JNK also increased G47Delta yield. In vivo, transient fasting (48-hour food restriction and 24-hour recovery) doubled luciferase activity after intratumoral G47Delta-US11fluc injection into orthotopic GBM xenografts. Thus, "transient fasting" increases G47Delta replication and oncolytic activity in human GBM cells. These results suggest that "transient fasting" may be effectively combined to enhance oncolytic HSV therapy of GBM. PMID- 27186406 TI - Hydroxylated collagen peptide in urine as biomarker for detecting colorectal liver metastases. AB - The clinical efficacy of carcinoembryonic antigen (CEA) as a marker of colorectal liver metastasis is limited, motivating a search for new biomarkers. Recently, urine proteomic analysis revealed AGPP(-OH)GEAGKP(-OH)GEQGVP(-OH)GDLGAP(-OH)GP (AGP), a promising peptide for this application. This study aimed to determine whether combining urine AGP testing with serum CEA analyses improves the sensitivity of detecting colorectal liver metastases. Urine samples from 100 patients with CRLM were collected prospectively and compared to three control groups: healthy kidney donors, patients who were relapse-free for 24 months after curative CRLM surgery, and primary colorectal cancer patients. A stable isotope labeled peptide standard was used to quantify the abundance of AGP in urine samples by selective reaction monitoring. Combined testing of urine AGP levels and serum CEA levels revealed a significantly increased sensitivity compared to CEA alone (85% vs. 68%, P<0.001; specificity 84% and 91%, respectively). No correlation was found between CEA and AGP-positive test results within individual patients (r(2) = 0.08). Urine AGP testing was negative in the three control groups. These results indicate that collagen-derived urine AGP peptide with a specific hydroxylation pattern combined with serum CEA levels may significantly improve the detection of colorectal liver metastases in patients at risk. PMID- 27186405 TI - HPV E6/p53 mediated down-regulation of miR-34a inhibits Warburg effect through targeting LDHA in cervical cancer. AB - MicroRNAs (miRNA) play crucial roles in regulating cell proliferation, differentiation and developmental timing. Aberrantly expressed miRNAs have recently emerged as key regulators of metabolism. However, little is known about its role in tumor metabolism of cervical cancer. In this study, we determined the oncogenic effects of miRNAs on Warburg effect, a metabolic phenotype that allows cancer cells to utilize glucose even under aerobic conditions. A gain-of-function study was performed in 12 down-regulated miRNAs that frequently reported in cervical cancer. We found that miR-34a plays a suppressive role in Warburg effect as evidenced by decreased lactate production and glucose consumption. Knockdown of oncoprotein E6 expression of human papillomavirus in SiHa and HeLa cells by siRNAs lead to an increased protein level of p53, decreased level of miR-34a, as well as reduced Warburg effect. Subsequently, lactate dehydrogenase A (LDHA), which catalyzes the last key step in glycolysis, was identified as a direct target of miR-34a. Silencing of LDHA or introduction of miR-34a significantly attenuated colony formation ability and invasive capacity of SiHa and HeLa cells, and these effects were fully compromised by reintroduction of LDHA. In conclusion, our findings demonstrated that deregulated miR-34a/LDHA axis induced by HPV E6/p53 signaling facilitates tumor growth and invasion through regulating Warburg effect in cervical cancer, and provided new insights into the mechanism by which miR-34a contributes to the development and progression of cervical cancer. PMID- 27186407 TI - The increased excretion of urinary orosomucoid 1 as a useful biomarker for bladder cancer. AB - Improving the early detection rate and prediction of bladder cancer remains a great challenge in management of this disease. To examine the value of urinary orosomucoid 1 (ORM1) for the early detection and surveillance of bladder cancer, two-dimensional differential gel electrophoresis (2-DE) and matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF/TOFMS) were applied to identify the differently expressed proteins in urine between bladder cancer and healthy controls. Thirteen different proteins including ORM1 were identified. After verification by western blotting, the ORM1 expressions were quantified in 186 urine samples by enzyme-linked immunosorbent assay (ELISA) correcting for creatinine expression. ELISA quantification showed the urinary ORM1-Cr was found to be higher in bladder cancer patients compared to controls and benign cases (7172.23+/-3049.67 versus 2243.16+/-969.01, 2493.48+/-830.37 ng/ml, respectively, P<0.0001). Furthermore, the pearson correlation analysis indicated that urinary ORM1 had high positive correlation with the pathology classification of bladder cancer. Receiver operating characteristic (ROC) analysis was used to calculate the cut-off value for early diagnosis of bladder cancer, and rendered an optimum cut-off value of 3912.97 ng/mg corresponding to 91.96% sensitivity and 94.34% specificity. Moreover, a cut-off value with 7351.28 ng/mg was utilized to distinguish infiltrating urothelial carcinoma from bladder cancer patients corresponding to 91.89% sensitivity and 90.67% specificity. In conclusion, our findings suggested the elevated urinary ORM1 could be a useful biomarker for bladder cancer. Further research is warranted to elucidate the pathogenic mechanisms of elevated ORM1. PMID- 27186408 TI - Association of CYP8A1 (Prostacyclin I2 synthase) polymorphism rs5602 with breast cancer in Mexican woman. AB - Breast cancer (BCa) is the most common cancer in Mexican women. Certain risk factors, such as environmental and lifestyle factors have been implicated in BCa initiation and progression. Moreover, genetic factors, such as single nucleotide polymorphisms (SNPs) of the P450 system, have been reported in BCa. In this report, and for the first time in the literature, we analyzed the rs5602 (67730 T > C) polymorphism in the CYP8A1 in patients with BCa and in healthy Mexican women to identify a potential risk between this polymorphism and BCa. Leukocyte cells from 38 control patients and tissue from radical mastectomy surgeries in 64 BCa patients were used for polymorphism analysis using an allelic discrimination assay with TaqMan probes. Links with clinic-pathological characteristics were also analyzed. Statistical analysis was performed using the standard chi(2) or Fisher exact test statistic. All CYP8A1 genotypes were detected in patients with BCa and the controls. Significant differences were observed in the distribution of CYP8A1 genotypes between the patients and controls (P=0.0008) and allele C was significantly associated with BCa risk (OR 2.08, 95% CI 1.166-3.72, P=0.0178). All polymorphism frequencies were in Hardy-Weinberg Equilibrium (HWE) in the controls (P > 0.05). We found that variant 67730 T > C was significantly associated with an increased risk of BCa (P < 0.05). We not observed an association of the TT and TC + CC genotypes with the clinical stage, BIRADS, estrogen receptor (ER) status, progesterone receptor (PR) status, HER2 status, p53 status, CD34 status, metastasis or therapy use. These results indicate that the CYP8A1 rs5602 SNP is a possible risk factor for BCa in Mexican women. This study showed an association between the CYP8A1 polymorphism and BCa risk in a Mexican population. PMID- 27186409 TI - Potentiation of chemotherapeutics by bromelain and N-acetylcysteine: sequential and combination therapy of gastrointestinal cancer cells. AB - Intraperitoneal chemotherapy together with cytoreductive surgery is the standard of care for a number of peritoneal surface malignancies. However, this approach fails to maintain the complete response and disease recurs due to microscopic residual disease. Although safer than systemic chemotherapy regimens, locoregional treatment with chemotherapeutics can induce toxicity which is a major concern affecting the patient's treatment protocol and outcome. For an enhanced treatment efficacy, efforts should be made to maximize cytotoxic effects of chemotherapeutic agents on tumor cells while minimizing their toxic effects on host cells. Bromelain and N-acetylcysteine are two natural agents with good safety profiles shown to have anti-cancer effects. However, their interaction with chemotherapeutics is unknown. In this study, we investigated if these agents have the potential to sensitize in vitro gastrointestinal cancer models to cisplatin, paclitaxel, 5-fluorouracil, and vincristine. The drug-drug interaction was also analyzed. Our findings suggest that combination of bromelain and N acetylcysteine with chemotherapeutic agents could give rise to an improved chemotherapeutic index in therapeutic approaches to peritoneal surface malignancies of gastrointestinal origin so that maximum benefits could result from less toxic and more patient-friendly doses. This represents a potentially efficacious strategy for the enhancement of microscopic cytoreduction and is a promising area for future research. PMID- 27186410 TI - Podoplanin - a small glycoprotein with many faces. AB - Podoplanin is a small membrane glycoprotein with a large number of O-glycoside chains and therefore it belongs to mucin-type proteins. It can be found on the surface of many types of normal cells originating from various germ layers. It is present primarily on the endothelium of lymphatic vessels, type I pneumocytes and glomerular podocytes. Increased levels of podoplanin or its neo-expression have been found in numerous types of human carcinomas, but it is especially common in squamous cell carcinomas, such as cervical, larynx, oral cavity, skin and lung cancer. This small sialomucin is also seen on the surface of cancer-associated fibroblasts (CAFs) in lung adenocarcinomas, as well as in breast and pancreatic tumors. In most cancers, a high level of podoplanin expression, both in cancer cells, as well as in CAFs, is correlated with an increased incidence of metastasis to lymph nodes and shorter survival time of patients. Little is known about the biological role of podoplanin, however research carried out on mice with a knock-out gene of this glycoprotein shows that the presence of podoplanin determines normal development of lungs, the lymphatic system and heart. Podoplanin on cancer cells and CAFs seems to play an important role in the development and progression of various cancers. However, its role in these processes is both unclear and controversial. In this review, the role of podoplanin in both physiological processes and carcinogenesis is discussed. PMID- 27186411 TI - Multifunctional DDX3: dual roles in various cancer development and its related signaling pathways. AB - DEAD-box RNA helicase 3 (DDX3) is a highly conserved family member of DEAD-box protein, which is a cluster of ATP-dependent and the largest family of RNA helicase. DEAD-box family is characterized by the regulation of ATPase and helicase activities, the modulation of RNA metabolism, and the actors of RNA binding proteins or molecular chaperones to interact with other proteins or RNA. For DDX3, it exerts its multifaceted roles in viral manipulation, stress response, hypoxia, radiation response and apoptosis, and is closely related to cancer development and progression. DDX3 has dual roles in different cancer types and can act as either an oncogene or tumor suppressor gene during cancer progression. In the present review, we mainly provide an overview of current knowledge on dual roles of DDX3 in various types of cancer, including breast cancer, lung cancer, colorectal cancer, hepatocellular carcinoma, oral squamous cell carcinoma, Ewing sarcoma, glioblastoma multiforme and gallbladder carcinoma, and illustrate the regulatory mechanisms for leading these two controversial biological effects. Furthermore, we summarize the essential signaling pathways that DDX3 participated, especially the Wnt/beta-catenin signaling and EMT related signaling (TGF-beta, Notch, Hedgehog pathways), which are crucial to DDX3 mediated cancer metastasis process. Thoroughly exploring the dual roles of DDX3 in cancer development and the essential signaling pathways it involved, it will help us open new perspectives to develop novel promising targets to elevate therapeutic effects and facilitate the "Personalized medicine" or "Precision medicine" to come into clinic. PMID- 27186413 TI - PTTG promotes invasion in human breast cancer cell line by upregulating EMMPRIN via FAK/Akt/mTOR signaling. AB - Pituitary tumor transforming gene (PTTG) is a novel oncogene that is expressed at higher level in most of the tumors. PTTG overexpression correlates with lymph node infiltration and a higher degree of tumor recurrence in breast cancer. However, the cellular functions and precise signals elicited by PTTG in breast cancer are not fully understood. Here, we established a breast cancer cell line which stably overexpressed PTTG. In vitro experiments showed that overexpression of PTTG in MCF-7 cells was associated with enhanced cell migration and invasion as well as EMT. Our results also demonstrated that PTTG overexpression correlated with elevated EMMPRIN level, which mediated the enhanced cell migration, invasion and EMT. Moreover, our findings suggested that PTTG enhances metastatic potential of breast cancer cells by inducing EMMPRIN through activating FAK/Akt/mTOR pathway. Our findings may lead to a better understanding of the biological effect of PTTG and provide mechanistic insights for developing potential therapeutic strategies for inhibiting the invasion and metastasis of breast cancer. PMID- 27186412 TI - CD19 chimeric antigen receptor (CD19 CAR)-redirected adoptive T-cell immunotherapy for the treatment of relapsed or refractory B-cell Non-Hodgkin's Lymphomas. AB - Recovery rates for B-cell Non-Hodgkin's Lymphoma (NHL) are up to 70% with current standard-of-care treatments including rituximab (chimeric anti-CD20 monoclonal antibody) in combination with chemotherapy (R-CHOP). However, patients who do not respond to first-line treatment or develop resistance have a very poor prognosis. This signifies the need for the development of an optimal treatment approach for relapsed/refractory B-NHL. Novel CD19- chimeric antigen receptor (CAR) T-cell redirected immunotherapy is an attractive option for this subset of patients. Anti-CD19 CAR T-cell therapy has already had remarkable efficacy in various leukemias as well as encouraging outcomes in phase I clinical trials of relapsed/refractory NHL. In going forward with additional clinical trials, complementary treatments that may circumvent potential resistance mechanisms should be used alongside anti-CD19 T-cells in order to prevent relapse with resistant strains of disease. Some such supplementary tactics include conditioning with lymphodepletion agents, sensitizing with kinase inhibitors and Bcl-2 inhibitors, enhancing function with multispecific CAR T-cells and CD40 ligand-expressing CAR T-cells, and safeguarding with lymphoma stem cell-targeted treatments. A therapy regimen involving anti-CD19 CAR T-cells and one or more auxiliary treatments could dramatically improve prognoses for patients with relapsed/refractory B-cell NHL. This approach has the potential to revolutionize B-NHL salvage therapy in much the same way rituximab did for first-line treatments. PMID- 27186414 TI - IL-17 induces EMT via Stat3 in lung adenocarcinoma. AB - Epithelial-mesenchymal transition (EMT) plays a vital role in lung inflammatory diseases, including lung cancer. However, the role and mechanism of action of the proinflammatory cytokine IL-17 in EMT in lung adenocarcinoma remain unresolved. In our study, we discovered that the expression of N-cadherin, Vimentin, Snail1, Snail2, and Twist1 was positively correlated with IL-17 expression, while E cadherin expression was negatively correlated with IL-17 expression in human lung adenocarcinoma tissues. Moreover, we confirmed that IL-17 promoted EMT in A549 and Lewis lung carcinoma (LLC) cells in vitro by upregulating N-cadherin, Vimentin, Snail1, Snail2, and Twist1 expression and downregulating E-cadherin expression. Stat3 was activated in IL-17-treated A549 and LLC cells, and Stat3 inhibition or siRNA knockdown notably reduced IL-17-induced EMT in A549 and LLC cells. Thus, IL-17 promotes EMT in lung adenocarcinoma via Stat3 signaling; these observations suggest that targeting IL-17 and EMT are potential novel therapeutic strategies for lung cancer. PMID- 27186415 TI - Plasma LUNX mRNA, a non-invasive specific biomarker for diagnosis and prognostic prediction of non-small cell lung cancer. AB - Lung cancer is the most common cancer worldwide. However, no specific biomarker has been found in diagnosis and evaluation of therapeutic efficacy for lung cancer. The human lung-specific X protein gene (LUNX) was recently identified with a feature of lung tissue specificity. We applied the fluorescent quantitative polymerase chain reaction method to examine LUNX mRNA in plasma and peripheral blood mononuclear cells (PBMC) in patients with non-small cell lung cancer (NSCLC), benign lung diseases, extrapulmonary tumors, and healthy subjects. The results showed that LUNX mRNA in both of plasma and PBMC were significantly higher in lung cancer patients compared to other groups. In plasma, there were higher sensitivity and negative predictive value of LUNX mRNA than in PBMC. Patients with III~IV stages of lung cancer had more LUNX mRNA in plasma than the early stage of lung cancer sufferers. After a period of therapy, significant reductions of plasma LUNX mRNA in patients with I and II stages of lung cancer were found. Levels of plasma LUNX mRNA in patients who had succeeded to respond to therapy decreased compared to prior treatment. On the other hand, the post-treatment level was obviously increased in patients that had failed to respond to therapy. Patients with negative plasma LUNX mRNA after therapy displayed a favorable prognosis and survival rate. These preliminary data suggested that cell-free LUNX mRNA in plasma as a non-invasive biomarker, is superior to peripheral intracellular LUNX mRNA, and plays a critical role in specific diagnosis and prognostic prediction of non-small cell lung cancer. PMID- 27186417 TI - PFKL/miR-128 axis regulates glycolysis by inhibiting AKT phosphorylation and predicts poor survival in lung cancer. AB - MicroRNAs (miRNAs) affect cancer cell glucose metabolism by targeting mRNAs of diverse enzymes that have been implicated in oxidative phosphorylation (OXPHOS) and glycolytic pathways. However, the mechanisms that underlie miRNA-mediated regulation of phosphofructokinase (PFK), a key rate-limiting enzyme in glycolysis, remain largely unknown. Here, we show that miR-128 directly targets PFK liver type (PFKL) in lung cancer cells and regulates endogenous expression of PFKL at both the mRNA and protein levels. In line with this, overexpression of miR-128 decreased glucose uptake and lactate production, as well as increased cellular ATP content. Interestingly, knockdown of miR-128 was shown to promote lung cancer cell growth and colony formation. Moreover, we observed that miR-128 expression inversely correlated with PFKL mRNA levels in clinic lung cancer samples and that increased PFKL expression predicted poor overall survival in lung cancer patients. Mechanistically, we showed that miR-128 regulates PFKL via a feedback loop that involves inhibition of the AKT signaling pathway. Together, our results suggest that miR-128 acts as a metabolic regulator in lung cancer cells that may be therapeutically exploited. PMID- 27186416 TI - Mesenchymal stem cell-derived exosomes facilitate nasopharyngeal carcinoma progression. AB - Mesenchymal stem cells (MSCs), which are capable of differentiating into multiple cell types, are reported to exert multiple effects on tumor development. However, the relationship between MSCs and nasopharyngeal carcinoma (NPC) cells remains unclear. Exosomes are small membrane vesicles that can be released by several cell types, including MSCs. Exosomes, which can carry membrane and cytoplasmic constituents, have been described as participants in a novel mechanism of cell-to cell communication. In the present study, we investigated the mechanisms underlying the interaction between MSCs and NPC cells. The data showed that MSCs secreted 40-100 nm heterogeneous small vesicles, which were defined as exosomes. Incubation of NPC cells with MSC-derived exosomes resulted in the uptake of exosomes by the cells, which promoted their proliferation, migration and tumorigenesis. After an extended treatment duration, the tumor cells showed morphological changes and significant changes in the expression of epithelial mesenchymal transition (EMT) markers. Moreover, we found that FGF19 was highly expressed in MSC-exosomes and that exosomes stimulated NPC progression by activating the FGF19-FGFR4-dependent ERK signaling cascade and by modulating the EMT. All of these data indicated that exosomes participate in a novel mechanism by which MSCs influence NPC progression. PMID- 27186418 TI - PRAS40 deregulates apoptosis in Ewing sarcoma family tumors by enhancing the insulin receptor/Akt and mTOR signaling pathways. AB - EWS expression in Ewing sarcoma family tumors (ESFTs) is decreased due to the haploinsufficiency elicited by chromosomal translocation. The abnormal expression levels of EWS and its downstream factors contribute to the manifestation of ESFTs. Previously, we reported that increased Proline-rich Akt substrate of 40 kDa (PRAS40), which is encoded by an EWS mRNA target, promotes the development of ESFTs. However, the mechanism remains elusive. To clarify the role of PRAS40 in ESFTs, we silenced PRAS40 expression in ESFT cells using siRNAs and found increased levels of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells. Cleaved caspase 3 levels and cytochrome C release were increased simultaneously. Furthermore, with PRAS40 knockdown, the phosphorylation of Akt and mTOR downstream factors, i.e., S6K and S6, was attenuated notably. Ectopic expression of PRAS40 increased Akt and S6 phosphorylation. Activation of Akt only partially reversed the apoptosis induced by PRAS40 knockdown, and downregulation of S6 phosphorylation by PRAS40 silencing could not be sufficiently restored via Akt activation. Searching the upstream factors in this pathway, the autophosphorylation of insulin receptor (IR) was found to be inhibited significantly by PRAS40 silencing but increased by PRAS40 overexpression. Therefore, PRAS40 may enhance IR phosphorylation to facilitate Akt and mTOR signaling leading to the apoptosis deregulation in ESFTs. Moreover, in vivo results confirmed that PRAS40 deletion suppressed the growth of ESFT xenografts and downregulated IR and S6 phosphorylation. Our findings suggest a novel functioning model for PRAS40, which represents a novel therapeutic target for ESFTs. PMID- 27186419 TI - Quercetin induces bladder cancer cells apoptosis by activation of AMPK signaling pathway. AB - Quercetin, a natural existing polyphenol compound, has shown anticancer capacity for liver, breast, nasopharyngeal and prostate carcinoma but has not been clinically approved yet. This might be due to lack of clear mechanistic picture. Bladder cancer is one of the most common cancers of the urinary tract in the world. In China, bladder cancer has the highest rate of incidence out of all malignancies of the urinary system. The anticancer application of quercetin on bladder cancer has not been investigated either. This study was aimed to examine the mechanisms of quercetin on inhibition of bladder cancer. First, two human and one murine bladder cancer cell lines were tested in vitro for inhibitory sensitivity by MTT and cologenic assays. Second, AMPK pathway including 4E-BP1 and S6K were examined by western blot. Quercetin induces apoptosis and inhibits migration. We are the first to show that quercetin displays potent inhibition on bladder cancer cells via activation of AMPK pathway. PMID- 27186420 TI - Over expression of hyaluronan promotes progression of HCC via CD44-mediated pyruvate kinase M2 nuclear translocation. AB - Hyaluronan is expressed in hepatocellular carcinoma (HCC) as HCC generally arises from a cirrhotic liver in which excessive production and accumulation of HA leads to developing cirrhosis. Though it has been suggested HA is involved in progression of HCC, the mechanisms underlying the connection between HA and HCC progression are unclear. Since increased aerobic glycolysis is a metabolic trait of malignant cells and HA-CD44 can modulate glucose metabolism, we aim to investigate the roles of PKM2, a key enzyme in glucose metabolism, in the HA-CD44 axis facilitated the progress of HCC. We shown PKM2 was required for HA-promoted HCC progression, which was not modulated by PKM2 kinase activity but by nuclear translocation of PKM2. PKM2 translocation was Erk (Thr202/Tyr204) phosphorylation dependent, which functioned at the downstream of HA-CD44 binding. Furthermore, elevated HA expression significantly correlated with PKM2 nuclear location and was an independent factors predicting poor HCC prognosis. In conclusions PKM2 nuclear translocation is required for mediating the described HA biological effects on HCC progression and our results imply that inhibition of HA may have therapeutic value in treating HCC. PMID- 27186421 TI - MiR-654-5p attenuates breast cancer progression by targeting EPSTI1. AB - MicroRNAs (miRNAs) dysregulation is a common event in a variety of human diseases including breast cancer. However, clinical relevance and biological role of miR 654-5p in the progression of breast cancer remain greatly elusive. Herein, the expression levels of miR-654-5p were aberrantly downregulated in human breast cancer specimens and four breast cancer cell lines. Low expression of miR-654-5p was strongly associated with advanced TNM stage and lymph node metastasis as well as a poor survival. Functional analysis showed that miR-654-5p overexpression inhibited cell growth and invasion, and induced cell apoptosis in two aggressive breast cancer cells. Further studies demonstrated that Epithelial stromal interaction 1 (EPSTI1) was a direct target gene of miR-654-5p and showed an inverse correlation with miR-654-5p expression. Forced expression of EPSTI1 could abrogate the inhibitory effect of miR-654-5p on the growth and invasion of breast cancer cells as well as apoptosis-induced ability. In conclusion, the present study highlights that miR-654-5p acts as a tumor suppressor in breast cancer through directly targeting EPSTI1, and their functional regulation may open a novel avenue with regard to the therapeutic target for breast cancer. PMID- 27186422 TI - Successful establishment of patient-derived tumor xenografts from gastrointestinal stromal tumor-a single center experience. AB - Patient-derived tumor xenografts (PDTX) generally represent a kind of more reliable model of human disease, by which a potential drugs' preclinical efficacy could be evaluated. To date, no stable gastrointestinal stromal tumor (GIST) PDTX models have been reported. In this study, we aimed to establish stable GIST PDTX models and to evaluate whether these models accurately reflected the histological feature of the corresponding patient tumors and create a reliable GIST PDTX models for our future experiment. By engrafting fresh patient GIST tissues into immune-compromised mice (BALB/c athymic mice), 4 PDTX models were established. Histological features were assessed by a qualified pathologist based on H&E staining, CD117 and DOG-1. We also conduct whole exome sequencing(WES) for the 4 established GIST PDTX models to test if the model still harbored the same mutation detected in corresponding patient tumors and get a more intensive vision for the genetic profile of the models we have established, which will help a lot for our future experiment. To explore the tumorigenesis mechanism for GIST, we also have a statistical analysis for the genes detected as nonsynchronous-mutated simultaneously in 4 samples. All 4 GIST PDTX models retained the histological features of the corresponding human tumors, with original morphology type and positive stains for CD117 and DOG-1. Between the GIST PDTX models and their parental tumors, a same mutation site was detected, which confirmed the genetic consistency. The stability of molecular profiles observed within the GIST PDTX models provides confidence in the utility and translational significance of these models for in vivo testing of personalized therapies. To date, we conducted the first study to successfully establish a GIST PDTX model whose genetic profiles were revealed by whole exome sequencing. Our experience could be of great use. PMID- 27186423 TI - Plasma levels of miRNA-155 as a powerful diagnostic marker for dedifferentiated liposarcoma. AB - Atypic lipomatous tumors (ALT) and dedifferentiated liposarcomas (DDLS) are closely related liposarcoma subtypes, often difficult to distinguish but they exhibit an entirely different clinical outcome. Recently discovered regulatory functions of miRNAs in liposarcoma progression prompted us to investigate miRNAs as potential diagnostic biomarkers in liposarcoma with a main focus on circulating miRNAs for fast and reliable differential diagnosis. Tumor and blood samples of 35 patients with lipomatous lesions collected between June 2011 and September 2014 were analyzed by qRT-PCR. They included 10 lipomas, 7 ALT, 5 DDLS and 13 myxoid liposarcomas (MLS). Ten samples of normal fat tissue and blood from 20 healthy volunteers were used as controls. A meta-analysis of public data on miRNA expression in liposarcoma revealed 9 miRNAs with potential diagnostic power. Out of these, miRNA-155 was found significantly elevated in the circulation of DDLS patients as compared to the plasma levels detected in all other liposarcoma subtypes and in healthy subjects. miRNA-155 levels in the plasma samples correlated significantly (r=0.41, p=0.02) with those in corresponding tumor extracts. This correlation was even more pronounced in an analysis of plasma and tumor extracts of malignant liposarcoma subtypes alone (r=0.51, p=0.02). Receiver operating characteristic analysis indicated that plasma miRNA-155 levels have a high diagnostic accuracy for distinguishing DDLS from healthy subjects (AUC=0.91, p=0.005) and from lipomas (AUC=0.86, p=0.02), MLS (AUC=0.92, p=0.006) and most importantly ALT (AUC=0.91, p=0.01) patients. In conclusion, this study identified miRNA-155 as a first blood biomarker for the differential diagnosis of DDLS. PMID- 27186424 TI - DNA methylation of oxidative stress genes and cancer risk in the Normative Aging Study. AB - Oxidative stress (OS) is a primary mechanism of carcinogenesis, and methylation of genes related to it may play a role in cancer development. In this study, we examined the prospective association between blood DNA methylation of four oxidative stress genes and cancer incidence. Our study population included a total of 582 participants in the Normative Aging Study (NAS) who had blood drawn during 1-4 visits from 1999-2012 (mean follow up 9.0 years). Promoter DNA methylation of CRAT, iNOS, OGG1 and GCR in blood leukocytes was measured using pyrosequencing. We used Cox regression models to examine prospective associations between cancer incidence and both methylation at the baseline visit and methylation rate of changes over time. Baseline OGG1 methylation was associated with higher risk of all-cancer (HR: 1.43, 95% CI: 1.15-1.78) and prostate cancer (HR: 1.52, 95% CI: 1.03-2.25) incidence. Compared with participants remaining cancer-free, those who eventually developed cancer had significantly accelerated CRAT methylation (p = 0.04) and decelerated iNOS methylation (p<0.01) over time prior to cancer diagnosis. Accelerated CRAT methylation was associated with higher all-cancer incidence (HR: 3.88, 95% CI: 1.06-14.30), whereas accelerated iNOS methylation was associated with lower all-cancer incidence (HR: 0.08, 95% CI 0.02-0.38). Our results suggest that methylation and its dynamic change over time in OS-related genes, including OGG1, CRAT and iNOS, may play an important role in carcinogenesis. These results can potentially facilitate the development of early detection biomarkers and new treatments for a variety of cancers. PMID- 27186426 TI - Paradoxical role of SOX2 in gastric cancer. AB - Sox2 is a critical regulator of embryogenesis and necessary for cellular reprogramming. It also plays an important role in tissue homeostasis and regeneration, maintaining the population of undifferentiated adult stem cells. Like various developmental and stem cell genes, SOX2 is aberrantly expressed and amplified in several human cancers. Moreover, functional studies have shown that it regulates many biological processes including cell proliferation, apoptosis, self-renewal and invasion. While it is oncogenic in most cancers, SOX2 activity is controversial in gastric cancer, where it might behave as a tumor suppressor in some situations. In this review, we discuss its role in cancer biology, with particular attention to what is known about the involvement of SOX2 in gastric cancer biology. PMID- 27186425 TI - The life and works of S100P - from conception to cancer. AB - Since its discovery in 1992, the small, 10.4 kDa calcium-binding protein S100P has gained the attention of researchers from different scientific fields due to its potential roles in both healthy and neoplastic tissues. Although not ubiquitously expressed, in tissues where it is present, S100P is associated with distinct changes in cellular behaviour. In this review we have summarized the evolutionary history of S100P, its expression and involvement in implantation and human embryonic development, as well as important functions in normal tissue and cancer. Finally, we have demonstrated its pivotal role as a potential diagnostic and therapeutic target, which opens promising avenues for further fruitful research on S100P. PMID- 27186427 TI - Anti-tumor efficacy of BEZ235 is complemented by its anti-angiogenic effects via downregulation of PI3K-mTOR-HIF1alpha signaling in HER2-defined breast cancers. AB - Activation of the PI3K-mTOR pathway via HER2: HER3-mediated signaling in HER2+ breast cancers pose one of the major threats towards the success of trastuzumab. First, trastuzumab cannot perturb survival/proliferative signals following HER2: HER3 heterodimerization in HER2+ tumor cells. Second, trastuzumab treatment has been reported to cause drug-mediated resistance in over 50% of HER2+ breast cancers. We have reported that treatment with an anti-angiogenic drug imparted a significant anti-tumor advantage when combined with trastuzumab plus pertuzumab in the trastuzumab-resistant model of HER2+ breast cancers (PMID: 23959459). The very fact as revealed by our study that an inclusion of anti-angiogenic drug conferred a significant anti-tumor advantage when combined with dual anti-HER2 therapy clearly indicated a critical and indispensable role of angiogenesis in these tumors. Hence, we hypothesized that BEZ235 a dual PI3K/mTOR inhibitor will have an effect on the tumor as well as the angiogenic stromal compartments. In vitro and in vivo efficacy of BEZ235 was determined in HER2+ trastuzumab sensitive, trastuzumab-resistant and HER2 amplified/PIK3CA mutated cell lines. BEZ235 alone and in combination with trastuzumab was tested on the tumor as well as stromal compartments. AKT-mTOR signal was suppressed following BEZ235 treatment in a concentration and time-dependent manner. AnnexinV, cl-CASPASE3, SURVIVIN and p-FOXO1 indicated that BEZ235-induced cell death occurred predominantly via an apoptotic pathway. Heregulin-induced HIF1alpha synthesis was also significantly decreased. Oncoprint data (cBioPortal) representing PAM50 Her2 enriched tumors (TCGA, Nature 2012) and Her2-positive breast tumors (TCGA, cell 2015) showed 91.4% genetic alterations and 79.2% genetic alterations in a set of four genes comprised of PIK3CA, ERBB2, VEGFA and HIF1alpha. The co-occurrence of HIF1alpha with VEGFA in PAM50 Her2 enriched tumors (TCGA, Nature 2012) and the co occurrence of HIF1alpha with VEGFA pair as well as HIF1alpha with PIK3CA pair in Her2-positive breast tumors (TCGA, cell 2015) were found statistically significant. In xenograft models, BEZ235 blocked tumor growth and decreased Ki67, CD31, p-AKT, p-S6RP, p-4EBP1 IHC-expressions. These decreases were more pronounced when BEZ235 was combined with trastuzumab in HER2+/trastuzumab sensitive, trastuzumab-resistant and HER2+/PIK3CA mutated models. We demonstrated that combined targeting of HER2 and the PI3K-AKT-mTOR pathway is superior to HER2 directed therapy alone. Mechanistically the inhibition of tumor-induced angiogenesis by BEZ235 caused by the down-regulation of PI3K-mTOR-HIF1alpha signaling irrespective of the trastuzumab-sensitivity status of HER2+ breast cancers proving evidence for the first time that the inhibition of angiogenesis is an important component of the anti-tumor efficacy of BEZ235 in HER2 defined breast cancers. PMID- 27186428 TI - A novel microtubule inhibitor, MT3-037, causes cancer cell apoptosis by inducing mitotic arrest and interfering with microtubule dynamics. AB - We investigated the anticancer potential of a new synthetic compound, 7-(3 fluorophenyl)-4-methylpyrido-[2,3-d]pyrimidin-5(8H)-one (MT3-037). We found that MT3-037 effectively decreased the cancer cell viability by inducing apoptosis. MT3-037 treatments led to cell cycle arrest at M phase, with a marked increase in both expression of cyclin B1 and cyclin-dependent kinase 1 (CDK1) as well as in CDK1 kinase activity. Key proteins that regulate mitotic spindle dynamics, including survivin, Aurora A/B kinases, and polo-like kinase 1 (PLK1), were activated in MT3-037-treated cells. MT3-037-induced apoptosis was accompanied by activation of a pro-apoptotic factor, FADD, and the inactivation of apoptosis inhibitors, Bcl-2 and Bcl-xL, resulting in the cleavage/activation of caspases. The activation of c-Jun N-terminal kinase (JNK) was associated with MT3-037 induced CDK1 and Aurora A/B activation and apoptosis. Immunofluorescence staining of tubulin indicated that MT3-037 altered tubulin networks in cancer cells. Moreover, an in vitro tubulin polymerization assay revealed that MT3-037 inhibited the tubulin polymerization by direct binding to tubulin. Molecular docking studies and binding site completion assays revealed that MT3-037 binds to the colchicine-binding site. Furthermore, MT3-037 significantly inhibited the tumor growth in both MDAMB-468 and Erlotinib-resistant MDA-MB-468 xenograft mouse models. In addition, MT3-037 inhibited the angiogenesis and disrupted the tube formation by human endothelial cells. Our study demonstrates that MT3-037 is a potential tubulin-disrupting agent for antitumor therapy. PMID- 27186429 TI - Chronic oxidative stress increases the integration frequency of foreign DNA and human papillomavirus 16 in human keratinocytes. AB - Cervical cancer is the second most common cancer, and the fourth most common cause of cancer death in women worldwide. Nearly all of these cases are caused by high-risk HPVs (HR HPVs), of which HPV16 is the most prevalent type. In most cervical cancer specimens, HR HPVs are found integrated into the human genome, indicating that integration is a key event in cervical tumor development. An understanding of the mechanisms that promote integration may therefore represent a unique opportunity to intercept carcinogenesis. To begin identifying these mechanisms, we tested the hypothesis that chronic oxidative stress (OS) induced by virus- and environmentallymediated factors can induce DNA damage, and thereby increase the frequency with which HPV integrates into the host genome. We found that virus-mediated factors are likely involved, as expression of E6*, a splice isoform of HPV16 E6, increased the levels of reactive oxygen species (ROS), caused oxidative DNA damage, and increased the frequency of plasmid DNA integration as assessed by colony formation assays. To assess the influence of environmentally induced chronic OS, we used L-Buthionine-sulfoximine (BSO) to lower the level of the intracellular antioxidant glutathione. Similar to our observations with E6*, glutathione depletion by BSO also increased ROS levels, caused oxidative DNA damage and increased the integration frequency of plasmid DNA. Finally, under conditions of chronic OS, we were able to induce and characterize a few independent events in which episomal HPV16 integrated into the host genome of cervical keratinocytes. Our results support a chain of events leading from induction of oxidative stress, to DNA damage, to viral integration, and ultimately to carcinogenesis. PMID- 27186431 TI - Prognostic significance of ubiquinol-cytochrome c reductase hinge protein expression in patients with clear cell renal cell carcinoma. AB - Ubiquinol-cytochrome c reductase hinge protein (UQCRH), as a connecter between cytochrome c1 with cytochrome c in complex III of respiratory chain, is top ranked hypermethylated gene in clear cell renal cell carcinoma (ccRCC). This study aims to evaluate the impact of UQCRH on recurrence and survival of 424 ccRCC patients enrolled retrospectively from a single institution after surgical resection using immunohistochemistry method. UQCRH was specifically downregulated in ccRCC, compared with papillary and chromophobe RCC. Moreover, patients with low UQCRH were prone to possess high T stage and TNM stage and associated with poor survival and early recurrence. UQCRH remained an independent favorable prognosticator for OS (Hazard rate [HR]: 0.510, 95% CI: 0.328-0.795, p=0.003) and RFS (HR: 0.506, 95% CI: 0.334-0.767, p=0.001) adjusting with other well established factors using backward Cox model. Furthermore, in stratified subgroups, patients with low UQCRH had an increased risk of recurrence (HR: 0.452, 95% CI: 0.261-0.783, p=0.005) and mortality (HR: 0.386, 95% CI: 0.205 0.726, p=0.003) in subgroup of early TNM stage. Taken together, UQCRH is a potential independent favorable prognostic factor for recurrence and survival of patients with ccRCC after nephrectomy. PMID- 27186430 TI - ALDH2 modulates autophagy flux to regulate acetaldehyde-mediated toxicity thresholds. AB - A polymorphic mutation in the acetaldehyde dehydrogenase 2 (ALDH2) gene has been epidemiologically linked to the high susceptibility to esophageal carcinogenesis for individuals with alcohol use disorders. Mice subjected to alcohol drinking show increased oxidative stress and DNA adduct formation in esophageal epithelia where Aldh2 loss augments alcohol-induced genotoxic effects; however, it remains elusive as to how esophageal epithelial cells with dysfunctional Aldh2 cope with oxidative stress related to alcohol metabolism. Here, we investigated the role of autophagy in murine esophageal epithelial cells (keratinocytes) exposed to ethanol and acetaldehyde. We find that ethanol and acetaldehyde trigger oxidative stress via mitochondrial superoxide in esophageal keratinocytes. Aldh2-deficient cells appeared to be highly susceptible to ethanol- or acetaldehyde-mediated toxicity. Alcohol dehydrogenase-mediated acetaldehyde production was implicated in ethanol-induced cell injury in Aldh2 deficient cells as ethanol-induced oxidative stress and cell death was partially inhibited by 4-methylpyrazole. Acetaldehyde activated autophagy flux in esophageal keratinocytes where Aldh2 deficiency increased dependence on autophagy to cope with ethanol-induced acetaldehyde-mediated oxidative stress. Pharmacological inhibition of autophagy flux by chloroquine stabilized p62/SQSTM1, and increased basal and acetaldehyde mediate oxidative stress in Aldh2 deficient cells as documented in monolayer culture as well as single-cell derived three-dimensional esophageal organoids, recapitulating a physiological esophageal epithelial proliferation differentiation gradient. Our innovative approach indicates, for the first time, that autophagy may provide cytoprotection to esophageal epithelial cells responding to oxidative stress that is induced by ethanol and its major metabolite acetaldehyde. Defining autophagymediated cytoprotection against alcohol-induced genotoxicity in the context of Aldh2 deficiency, our study provides mechanistic insights into the tumor suppressor functions of ALDH2 and autophagy in alcohol-related esophageal carcinogenesis. PMID- 27186432 TI - M2698 is a potent dual-inhibitor of p70S6K and Akt that affects tumor growth in mouse models of cancer and crosses the blood-brain barrier. AB - Dysregulated PI3K/Akt/mTOR (PAM) pathway signaling occurs in ~30% of human cancers, making it a rational target for new therapies; however, the effectiveness of some PAM pathway inhibitors, such as mTORC rapalogs, may be compromised by a compensatory feedback loop leading to Akt activation. In this study, the p70S6K/Akt dual inhibitor, M2698 (previously MSC2363318A), was characterized as a potential anti-cancer agent through examination of its pharmacokinetic, pharmacodynamic and metabolic properties, and anti-tumor activity. M2698 was highly potent in vitro (IC50 1 nM for p70S6K, Akt1 and Akt3 inhibition; IC50 17 nM for pGSK3beta indirect inhibition) and in vivo (IC50 15 nM for pS6 indirect inhibition), and relatively selective (only 6/264 kinases had an IC50 within 10-fold of p70S6K). Orally administered M2698 crossed the blood-brain barrier in rats and mice, with brain tumor exposure 4-fold higher than non disease brain. Dose-dependent inhibition of target substrate phosphorylation was observed in vitro and in vivo, indicating that M2698 blocked p70S6K to provide potent PAM pathway inhibition while simultaneously targeting Akt to overcome the compensatory feedback loop. M2698 demonstrated dose-dependent tumor growth inhibition in mouse xenograft models derived from PAM pathway-dysregulated human triple-negative (MDA-MB-468) and Her2-expressing breast cancer cell lines (MDA-MB 453 and JIMT-1), and reduced brain tumor burden and prolonged survival in mice with orthotopically implanted U251 glioblastoma. These findings highlight M2698 as a promising PAM pathway inhibitor whose unique mechanism of action and capacity to pass the blood-brain barrier warrant clinical investigation in cancers with PAM pathway dysregulation, and those with central nervous system involvement. PMID- 27186433 TI - Bruceine D induces apoptosis in human chronic myeloid leukemia K562 cells via mitochondrial pathway. AB - Chronic myeloid leukemia (CML), an acquired malignant myeloproliferative disorder of hematopoietic stem cells, is one of the three most common forms of leukemia. In this study, we investigated the effects of bruceine D, which have been isolated from Brucea javanica (L.) Merr. on human chronic myeloid leukemia K562 cells. MTT assay was used to evaluate cell growth inhibition. Flow cytometry was performed to analyze mitochondrial membrane potential (DeltaPsim). Western blot was applied to detect expression of cytochrome c, caspases-9, -3, PARP and other proteins. Bruceine D exhibited potent cytotoxicity to K562 cells with IC50 of 6.37 +/- 0.39 MUM. It led to loss of DeltaPsim, release of cytochrome c, activation of caspases-9, -3 and cleavage of PARP, which suggested that bruceine D induced apoptosis of K562 cells through mitochondrial pathway. In addition, bruceine D inhibited the phosphorylation of AKT and ERK. It's indicative that the potent anticancer activity of bruceine D be related to MAPK and PI3K pathways. PMID- 27186435 TI - In vitro and in vivo antiangiogenic activity of desacetylvinblastine monohydrazide through inhibition of VEGFR2 and Axl pathways. AB - Tumor angiogenic process is regulated by multiple proangiogenic pathways, such as vascular endothelial growth factor receptor 2 (VEGFR2) and Axl receptor tyrosine kinase (Axl). Axl is one of many important factors involved in anti-VEGF resistance. Inhibition of VEGF/VEGFR2 signaling pathway alone fails to block tumor neovascularization. Therefore, discovery of novel agents targeting multiple angiogenesis pathways is in demand. Desacetylvinblastine monohydrazide (DAVLBH), a derivative of vinblastine (VLB), has been reported exhibit an anticancer activity via its cytotoxic effect. However, little attention has been paid to the antiangiogenic properties of DAVLBH. Here, we firstly reported that DAVLBH exerted a more potent antiangiogenic effect than VLB in vitro and in vivo, which was associated with inactivation of VEGF/VEGFR2 and Gas6/Axl signaling pathways. We found that DAVLBH inhibited VEGF- and Gas6-induced HUVECs proliferation, migration, tube formation and vessel sprouts formation in vitro and ex vivo. It significantly inhibited in vivo tumor angiogenesis and tumor growth in HeLa xenografts. It also inhibited Gas6-induced pericytes recruitment to endothelial tubes accompanied with a decrease in expression and activation of Axl. Besides, it could block the compensatory up-regulating expression and activation of Axl in response to bevacizumab treatment in HUVECs. Taken together, our results suggest that DAVLBH potently inhibits angiogenesis-mediated tumor growth through blockage of the activation of VEGF/VEGFR2 and Gas6/Axl pathways and it might serve as a promising antiangiogenic agent for the cancer therapy. PMID- 27186437 TI - Erratum: Upregulation of H19 indicates a poor prognosis in gallbladder carcinoma and promotes epithelial-mesenchymal transition. AB - [This corrects the article on p. 15 in vol. 6, PMID: 27073719.]. PMID- 27186434 TI - Regulation of therapeutic resistance in cancers by receptor tyrosine kinases. AB - In response to DNA damage lesions due to cellular stress, DNA damage response (DDR) pathways are activated to promote cell survival and genetic stability or unrepaired lesion-induced cell death. Current cancer treatments predominantly utilize DNA damaging agents, such as irradiation and chemotherapy drugs, to inhibit cancer cell proliferation and induce cell death through the activation of DDR. However, a portion of cancer patients is reported to develop therapeutic resistance to these DDR-inducing agents. One significant resistance mechanism in cancer cells is oncogenic kinase overexpression, which promotes cell survival by enhancing DNA damage repair pathways and evading cell cycle arrest. Among the oncogenic kinases, overexpression of receptor tyrosine kinases (RTKs) is reported in many of solid tumors, and numerous clinical trials targeting RTKs are currently in progress. As the emerging trend in cancer treatment combines DNA damaging agents and RTK inhibitors, it is important to understand the substrates of RTKs relative to the DDR pathways. In addition, alteration of RTK expression and their phosphorylated substrates can serve as biomarkers to stratify patients for combination therapies. In this review, we summarize the deleterious effects of RTKs on the DDR pathways and the emerging biomarkers for personalized therapy. PMID- 27186436 TI - Tumour-specific metabolic adaptation to acidosis is coupled to epigenetic stability in osteosarcoma cells. AB - The glycolytic-based metabolism of cancers promotes an acidic microenvironment that is responsible for increased aggressiveness. However, the effects of acidosis on tumour metabolism have been almost unexplored. By using capillary electrophoresis with time-of-flight mass spectrometry, we observed a significant metabolic difference associated with glycolysis repression (dihydroxyacetone phosphate), increase of amino acid catabolism (phosphocreatine and glutamate) and urea cycle enhancement (arginino succinic acid) in osteosarcoma (OS) cells compared with normal fibroblasts. Noteworthy, metabolites associated with chromatin modification, like UDP-glucose and N(8)-acetylspermidine, decreased more in OS cells than in fibroblasts. COBRA assay and acetyl-H3 immunoblotting indicated an epigenetic stability in OS cells than in normal cells, and OS cells were more sensitive to an HDAC inhibitor under acidosis than under neutral pH. Since our data suggest that acidosis promotes a metabolic reprogramming that can contribute to the epigenetic maintenance under acidosis only in tumour cells, the acidic microenvironment should be considered for future therapies. PMID- 27186439 TI - Prognostic value of FDG PET/CT-based metabolic tumor volumes in metastatic triple negative breast cancer patients. AB - FDG PET/CT-based measures of tumor burden show promise to predict survival in patients with metastatic breast cancer, but the patient populations studied so far are heterogeneous. The reports may have been confounded by the markedly different prognosis of the various subtypes of breast cancer. The purpose of this study is to evaluate the correlation between tumor burden on FDG PET/CT and overall survival (OS) in patients within a defined population: metastatic triple negative breast cancer (MTNBC). FDG PET/CT scans of 47 consecutive MTNBC patients (54+/-12 years-old) with no other known malignancies were analyzed. A total 393 lesions were identified, and maximum standardized uptake value (SUVmax), mean SUV, metabolic tumor volume (MTV), total lesion number (TLN) and total lesion glycolysis (TLG), were measured and correlated with patient survival by Mantel Cox tests and Cox regression analysis. At a median follow-up time of 12.4 months, 41 patients died with a median OS of 12.1 months. Patients with MTV less than 51.5 ml lived nearly three times longer (22 vs 7.1 months) than those with a higher MTV (chi(2)=21.3, P<0.0001). In a multivariate Cox regression analysis only TLN and MTV were significantly correlated with survival. Those with an MTV burden in the 75(th) percentile versus the 25(th) percentile had a hazard ratio of 6.94 (p=0.001). In patients with MTNBC, MTV appears to be a strong prognostic factor. If validated in prospective studies, MTV may be a valuable tool for risk stratification of MTNBC patients in clinical trials and to guide patient management. PMID- 27186438 TI - PET imaging of in vivo caspase-3/7 activity following myocardial ischemia reperfusion injury with the radiolabeled isatin sulfonamide analogue [(18)F]WC-4 116. AB - The utility of [(18)F]WC-4-116, a PET tracer for imaging caspase-3 activation, was evaluated in an animal model of myocardial apoptosis. [(18)F]WC-4-116 was injected into rats at 3 hours after a 30 min period of ischemia induced by temporary occlusion of the left anterior descending coronary artery in Sprague Dawley rats. [(18)F]WC-4-116 uptake was quantified by 1) autoradiography, 2) microPET imaging studies, and 3) post-PET biodistribution studies. MicroPET imaging also assessed uptake of the non-caspase-3-targeted tracer [(18)F]ICMT-18 at 3 hours postischemia. Enzyme assays and Western blotting assessed caspase-3 activation in both at-risk and not-at-risk regions. Caspase-3 enzyme activity increased in the at-risk but not in the not-at-risk myocardium. Quantitative autoradiographic analysis of [(18)F]WC-4-116 demonstrated nearly 2-fold higher uptake in the ischemia-reperfusion (IR) versus sham animals. [(18)F]WC-4-116 microPET imaging studies demonstrated that the IR animals was similarly elevated in relation to sham. [(18)F]ICMT-18 uptake did not increase in at-risk myocardium despite evidence of caspase-3 activation. Biodistribution studies with [(18)F]WC 4-116 confirmed the microPET findings. These data indicate that the caspase-3-PET tracer [(18)F]WC-4-116 can noninvasively image in vivo caspase activity during myocardial apoptosis and may be useful for clinical imaging in humans. PMID- 27186440 TI - What role for radiobiphosphonates bone scintigraphy in the monitoring of an unusual bone giant cell tumor: a case report and literature review. AB - We report the case of 24 years old female patient, followed since ten years ago for bone giant cell tumor (GCT) of the right knee, which was complicated by pulmonary metastases. Surgical treatment and pulmonary metastasectomies have not allowed definitive cure of this disease with the appearance of metachronous bone lesions after eight years of evolution. The literature review confirms the originality of this observation: the age of the patient, the initial and metastasis locations and the occurrence of lung metastases with unfavorable prognosis. Through this clinical case, the authors highlight the role of radiobiphosphonates bone scintigraphy in detecting synchronous or metachronous bone lesions, and in monitoring of these locations under medical treatment. PMID- 27186441 TI - Good manufacturing practice production of [(68)Ga]Ga-ABY-025 for HER2 specific breast cancer imaging. AB - Therapies targeting human epidermal growth factor receptor type 2 (HER2) have revolutionized breast cancer treatment, but require invasive biopsies and rigorous histopathology for optimal patient stratification. A non-invasive and quantitative diagnostic method such as positron emission tomography (PET) for the pre-therapeutic determination of the presence and density of the HER2 would significantly improve patient management efficacy and treatment cost. The essential part of the PET methodology is the production of the radiopharmaceutical in compliance with good manufacturing practice (GMP). The use of generator produced positron emitting (68)Ga radionuclide would provide worldwide accessibility of the agent. GMP compliant, reliable and highly reproducible production of [(68)Ga]Ga-ABY-025 with control over the product peptide concentration and amount of radioactivity was accomplished within one hour. Two radiopharmaceuticals were developed differing in the total peptide content and were validated independently. The specific radioactivity could be kept similar throughout the study, and it was 6-fold higher for the low peptide content radiopharmaceutical. Intrapatient comparison of the two peptide doses allowed imaging optimization. The high peptide content decreased the uptake in healthy tissue, in particular liver, improving image contrast. The later imaging time points enhanced the contrast. The combination of high peptide content radiopharmaceutical and whole-body imaging at 2 hours post injection appeared to be optimal for routine clinical use. PMID- 27186443 TI - In vivo injection of alpha-bungarotoxin to improve the efficiency of motor endplate labeling. AB - INTRODUCTION: Motor endplates are composed of a motor neuron terminal and muscle fiber and are distributed in skeletal muscle, causing muscle contraction. However, traditional motor endplate staining methods are limited to the observation of partial skeletal muscle. The procedure was time-consuming due to strict incubation conditions, and usually provided unsatisfactory results. We explored a novel method to label motor endplate rapidly by in vivo injection of fluorescent alpha-bungarotoxin. METHODS: Fifty-two mice were randomly divided into two groups, an experiment group (n = 50), and a contrast group (n = 2). In experiment group, alpha-bungarotoxin was injected via the caudal vein. The injection dosages were designated as 0.1, 0.2, 0.3, 0.4, and 0.5 MUg/g. The experimental mice were divided into five subgroups of ten mice per group. The contrast group was only injected with 200 MUL normal saline solution. Bilateral gastrocnemius were acquired for microscope analysis and optical clearing to seek specific fluorescent signal. RESULTS: A dose of 0.3 MUg/g of alpha-bungarotoxin with 1 h conjugation time could display the number and structure of motor endplate in plane view. Compared with the traditional procedure, this method was rapid, convenient, and time-saving. Combined with the optical clearing technique, spatial distribution could also be seen, helping to better understand the stereoscopic view of motor endplate position in skeletal muscle. CONCLUSIONS: In vivo injection of alpha-bungarotoxin proved effective for studying motor endplate in skeletal muscle. PMID- 27186442 TI - Is peripheral paraneoplastic neurological syndrome possible in primary brain tumors? AB - INTRODUCTION: Systemic malignant diseases cause the induction of autoimmunity, for example, paraneoplastic syndromes. There are no proofs of paraneoplastic syndromes in primary brain tumors. The aim of the study was to evaluate the involvement of the peripheral nervous system, together with an assessment of onconeuronal and antineural antibodies as indicators of humoral immune response against nervous system in patients with primary brain tumors. MATERIALS AND METHODS: Clinical examinations, electrophysiological studies of peripheral nerves (motor and sensory conduction velocity studies, conduction velocity distribution tests, thermal and vibratory quantitative sensory tests, and sympathetic skin response tests) and muscles, blood sampling collection (assessment of onconeuronal, and antineural antibodies) were performed on 33 patients with newly recognized primary brain tumors within 2-4 days after their admission to our department. RESULTS: We revealed statistically significant changes of peripheral nerves, more pronounced in the peroneal nerve in standard and conduction velocity distribution tests, as well as in sympathetic skin responses. We revealed significantly higher vibratory thresholds, and pain thresholds for cold and warm in the upper and lower limbs in the study group than in the controls. In five patients, we have identified anti-neuroendothelium, anti-GFAP, anti-MAG, anti PCNA, and anti-Ro52 antibodies. CONCLUSIONS: In patients with primary brain tumors, electrophysiological changes in peripheral nerves, together with the presence of the antineural antibodies suggest an autoimmune humoral response, and make the diagnosis of paraneoplastic neurological syndrome possible. PMID- 27186444 TI - Prognostic significance of carotid and vertebral ultrasound in ischemic stroke patients. AB - OBJECTIVES: The ultrasound investigation of carotid and vertebral arteries is routinely performed in stroke patients to determine the etiopathogenetic classification and possible need of revascularization. However, the medium and long-term prognostic implications of carotid and vertebral ultrasound in ischemic stroke patients are not yet known. METHODS: This study included 309 ischemic stroke patients (mean age 76.3; 160 men). They all had undergone carotid and vertebral ultrasound (carotid stenoses were measured according to the European Carotid Surgery Trial [ECST] method). After a median interval of 9.4 months, a telephone follow-up was performed to determine their outcome. Dependency or death (modified Rankin scale-mRS >2) and all cause mortality were the study end-points. RESULTS: At follow-up, 158 patients had a mRS >2. In multivariate analysis, of 13 variables univariately predictive of dependency or death, only National Institutes of Health Stroke Scale (NIHSS) score (P < 0.0001), age (P < 0.0001) and ipsi- or contralateral carotid stenosis >=60% (O.R. 3.5, 95% C.I. 1.5-8.6, P = 0.006) remained associated with a mRS >2. Sixty-nine patients had died. In a Cox proportional hazards regression, of 10 variables univariately predictive of mortality, only NIHSS score (P < 0.0001), age (P = 0.003), total anterior circulation syndrome (P = 0.004), vertebral Doppler abnormalities (O.R. 2.2, 95% C.I. 1.3-3.6, P = 0.006), male sex (P = 0.02), and hypercholesterolemia (P = 0.04, inverse relationship) remained associated with mortality. CONCLUSIONS: In stroke patients, carotid stenoses >=60%, ipsi- or contralateral to cerebral lesions, were associated with an increased medium and long-term probability of dependency or death, and abnormalities of vertebrobasilar flow were a significant indicator of death risk, independent of stroke severity and age. PMID- 27186445 TI - Ventilation-Based Decellularization System of the Lung. AB - The demand for donated organs greatly exceeds the availability. Alternatives to organ donation, such as laboratory-engineered organs, are therefore being developed. One approach is to decellularize the organ and reseed it with selected cells, ideally from the organ recipient. Organ decellularization has typically been attempted by the administration of detergents into vessels such as the portal vein in the liver. However, in the case of the lung, the airway provides another potential administration route, because it has a wide contact area between cells and detergents in the tracheal tree and alveoli. In the present study, we introduce a novel ventilation-based decellularization system for the lung and compare its efficacy to ordinary decellularization systems administering detergent through the pulmonary artery. Rat lungs were decellularized using 500 mL of 3-[(3-cholamidopropyl) dimethylammonio]-1-Propanesulfonate (CHAPS) decellularization solution administrated through the pulmonary artery (vessel group) or through the trachea (airway group). The vessel group was infused CHAPS solution using a gravitational pressure head of 20 cmH2O. The airway group was infused with the detergent using negative pressure and positive end-expiratory pressure, for a volume 10cc with each inspiration in a bioreactor. Pathological and immunohistochemical findings indicated that components of the extracellular matrix (ECM), including proteoglycans, elastic fibers, fibronectin, and laminin, were more decreased in the airway group than in the vessel group. Western blot analysis showed that MHC class I antigen and beta-actin were not detected in both decellularized groups. A collagen assay showed that collagen was 70% preserved in both groups compared to native lung. Glycosaminoglycan (GAG) and DNA assays showed that GAG and DNA contents were strongly diminished in both decellularized groups, but those contents were smaller in the airway group than in the vessel group. Accordingly, the alveolar wall was thinner on electron microscopy, and DNA remnants were not observed in the airway group. Infusion of red blood cells indicated that capillary walls were preserved without blood leakage in both groups. In conclusion, we describe a novel approach for decellularization through the airway that represents a more stringent method for both DNA and ECM removal, with capillary wall preservation. PMID- 27186446 TI - Novel Links between Troubled Marriages and Appetite Regulation: Marital Distress, Ghrelin, and Diet Quality. AB - Distressed marriages enhance risk for health problems; appetite dysregulation is one potential mechanistic pathway. Research suggests that ghrelin and leptin, appetite-relevant hormones connected to shorter and longer-term energy balance, may differentially affect people with a higher versus lower body mass index (BMI). During this double-blind randomized crossover study, both members of a couple (N=86 participants) ate a standardized meal at the beginning of two visits. Observational recordings of a marital conflict assessed marital distress. Ghrelin and leptin were sampled pre-meal and post-meal at 2, 4, and 7 hours. Diet quality was measured using the USDA 24-Hour Multiple-Pass Approach. People in more distressed marriages had higher post-meal ghrelin (but not leptin) and a poorer quality diet than those in less distressed marriages, but only among participants with a lower BMI. These effects were consistent for both spouses. Ghrelin and diet quality may link marital distress to its corresponding negative health effects. PMID- 27186447 TI - Molecular Imaging in Genetic Medicine. AB - The field of biomedical imaging has made significant advances in recent times. This includes extremely high-resolution anatomic imaging and functional imaging of physiologic and pathologic processes as well as novel modalities in optical imaging to evaluate molecular features within the cellular environment. The latter has made it possible to image phenotypic markers of various genotypes that are implicated in human development, behavior, and disease. This article discusses the role of molecular imaging in genetic and precision medicine. PMID- 27186448 TI - Demographics of Lower Limb Amputations in the Pakistan Military: A Single Center, Three-Year Prospective Survey. AB - INTRODUCTION : The Pakistan military has been actively engaged in the war against terror for more than a decade. Many officers and soldiers have lost their limbs in this war. But the data on traumatic lower limb amputations in Pakistan is sparse. The aim of this study is to prospectively document the epidemiological profile of lower limb military amputees presenting at the largest rehabilitation centre of Pakistan over a three-year period. MATERIALS & METHODS : A prospective three-year survey was conducted at the Armed Forces Institute of Rehabilitation Medicine (AFIRM), Pakistan. One hundred twenty-three consecutive patients with lower limb amputations were enrolled in the survey. The demographic data, etiology, associated injuries, complications profile, and type of prosthesis provided were documented. The data analysis was done using the statistical analysis tool SPSS V 20 (IBM(r),NY, USA). RESULTS : All patients were male. Most had traumatic amputation (119), were between 20-40 years (106), with unilateral amputation (115). Mine blast injury was the leading cause in 73 (59.3%) and most (58.5%) were fitted with modular prosthesis. Transtibial amputation was the commonest level (65), followed by transfemoral (30). The time of surgical amputation was not documented in 87% of the patients. Half of the patients (54%) had associated injuries. Seventy-nine patients had at least one complication with phantom pain being the commonest in 25% cases. CONCLUSIONS : This is the largest prospective demographic survey of lower limb amputees in Pakistan military to date. Scores of soldiers and civilians in Pakistan have suffered lower limb amputation. The availability of demographic data can improve the trauma and rehabilitation services for better understanding and management of such cases. There is a need to conduct large scale community-based epidemiological surveys to direct future policies and develop amputee rehabilitation services in the public sector. PMID- 27186449 TI - Patterns of Care and Outcomes of Adjuvant Radiotherapy for Meningiomas: A Surveillance, Epidemiology, and End Results and Medicare Linked Analysis. AB - BACKGROUND: The role of adjuvant stereotactic radiosurgery (SRS) and fractionated radiotherapy (XRT) are unknown in patients with resected meningiomas. OBJECTIVE: To identify patterns of care and outcomes of adjuvant radiotherapy for meningiomas in the Linked Surveillance, Epidemiology, and End Results (SEER) Medicare data. METHODS: A total of 1,964 patients older than 66 years included in the SEER-Medicare data, who were diagnosed with meningioma, and underwent craniotomy were included for analysis. RESULTS: Patients were less likely to receive adjuvant therapy if they were older than 75 (OR 0.730, 95% CI 0.548 0.973), female sex (OR 0.731, 95% CI 0.547-0.978), or unmarried (OR 0.692, 95% CI 0.515-0.929). Patients were more likely to receive adjuvant treatment for Grade II/III tumors (OR 5.586, 95% CI 2.135-13.589), tumors over 5 cm (OR 1.850, 95% CI 1.332-2.567), or partial resection (OR 3.230, 95% CI 2.327-4.484). Yearly between 2000 and 2009, 10.65 - 19.77% of patients received adjuvant therapy. Although no survival benefit was seen with the addition of adjuvant therapy (p = 0.1236), the subgroup of patients receiving SRS had a decreased risk of death compared to those receiving surgery alone (aHR 0.544, 95% CI 0.318 - 0.929). CONCLUSION: Utilization of adjuvant XRT and SRS remained stable between 2000 and 2010. Male sex, young age, marriage, partial resection, Grade II/III tumors, and large tumors predicted the use of adjuvant therapy. For all patients, SRS decreased the risk of death compared to craniotomy alone. PMID- 27186450 TI - Sweet Syndrome Associated with Upper Respiratory Infection and Amoxicillin Use. AB - Sweet syndrome (acute febrile neutrophilic dermatosis) is an uncommon dermatologic eruption characterized by acute onset of painful papules, plaques or nodules on the skin that are red, blue, or violaceous in color. It has been associated with various infections, medications, and malignancies. Here we report the case of a middle-aged male who presents with Sweet syndrome after an upper resipiratory infection and while using amoxicillin. We also review the diagnostic criteria, laboratory testing, and treatment options. PMID- 27186452 TI - Fetal MRI as Complementary Study of Congenital Cystic Adenomatoid Malformation During Pregnancy: A Single Case Report. AB - Fetal lung masses are rare findings in prenatal ultrasound scanning in general population, of which congenital cystic adenomatoid malformation is the most commonly diagnosed type. This paper reports a single case of congenital cystic adenomatoid malformation detected at our hospital and the subsequent clinical follow-up using ultrasound scanning and fetal magnetic resonance imaging. PMID- 27186451 TI - Standardized Photographic Views in Oculoplastic Surgery: How to Capture Quality Images Outside a Photographic Studio. AB - Purpose The aim of this paper is to demonstrate fundamental photographic techniques and standardized views in oculoplastic disease and surgery outside of a photographic studio. Methods A Canon EOS 60D digital single lens reflex (DSLR) camera, which was fitted with a Canon EF-S 60 mm USM macro lens, was used to photograph the subject. A Canon MR-14EX Macro Ringlite was used to illuminate the subject. Informed written consent was obtained for publication of the photographs used in this study. The photographs were taken in an ophthalmology clinic using standardized photographic settings at various magnification ratios. The magnification ratios were recalibrated and adjusted to accommodate the smaller sensor size in-line with standardized medical photography guidelines. Results We present a series of core views for various oculoplastic and orbital disease presentations. Conclusions It is possible to capture quality standardized digital photographs in a busy clinical environment without the need for a dedicated photographic studio. PMID- 27186453 TI - Frameless Stereotactic Radiosurgery, a Feasible Alternative to the Frame-Based Technique for the Treatment of Refractory Trigeminal Neuralgia. AB - Classic trigeminal neuralgia (TN) causes severe facial pain. Several treatment options exist for classic TN refractory to medical therapy, including stereotactic radiosurgery (SRS). Most studies in the medical literature used a frame-based SRS technique. Improvements in linear accelerator-based treatment systems and image guidance have led to the use of frameless SRS as a safe and feasible alternative to the frame-based technique for the treatment of refractory TN. We present a case of refractory TN successfully treated with frameless SRS. PMID- 27186455 TI - Comparison of net ecosystem carbon exchange estimation in a mixed temperate forest using field eddy covariance and MODIS data. AB - Quantification of net ecosystem carbon exchange (NEE) between the atmosphere and vegetation is of great importance for regional and global studies of carbon balance. The eddy covariance technique can quantify carbon budgets and the effects of environmental controls for many forest types across the continent but it only provides integrated CO2 flux measurements within tower footprints and need to be scaled up to large areas in combination with remote sensing observations. In this study we compare a multiple-linear regression (MR) model which relates enhanced vegetation index and land surface temperature derived from the moderate resolution imaging spectroradiometer (MODIS), and photosynthetically active radiation with the site-level NEE, for estimating carbon flux exchange between the ecosystem and the environment at the deciduous-dominated Harvard Forest to three other methods proposed in the literature. Six years (2001-2006) of eddy covariance and MODIS data are used and results show that the MR model has the best performance for both training (2001-2004, R (2) = 0.84, RMSE = 1.33 g Cm(-2) day(-1)) and validation (2005-2006, R (2) = 0.76, RMSE = 1.54 g Cm(-2) day(-1)) datasets comparing to the other ones. It provides the potential to estimate carbon flux exchange across different ecosystems at various time intervals for scaling up plot-level NEE of CO2 to large spatial areas. PMID- 27186456 TI - Effects of the seasonal flooding on riparian soil seed bank in the Three Gorges Reservoir Region: a case study in Shanmu River. AB - INTRODUCTION: The water-level fluctuation in the Three Gorges Reservoir Region has changed dramatically as a result of the hydroelectric project for flood control and power generation. The riparian seasonal hydrological environment also has changed from summer flooding with winter drought to summer drought with winter flooding. The changes of riparian seed bank and vegetation were investigated to determine the effects of the seasonal flooding on the composition and spatial distribution of riparian soil seed bank and the similarity of seed bank to standing vegetation. CASE DESCRIPTION: We conducted intensive riparian soil sampling (525 samples) along altitude gradient in the Shanmu River, a tributary of the Yangzi River in the reservoir region of China. Seed bank density, species richness and composition of soil seed bank were examined using the seedling-emergence method. The seasonal hydrological conditions resulted in a decrease in species diversity and an increase in the distribution heterogeneity of the soil seed bank. The soil seed bank was composed of 48 species from 22 families and 40 genera. Most species were annual and perennial herbaceous Polygonaceae, Asteraceae, and Poaceae. Rumex dentatus was the predominant species accounting for 27.0 % of the total seeds. Diversity and composition of the seed bank changed along an altitude gradient and soil depth. Maximum species richness was found in the top soil layer at 165 m and 175 m above sea level. The mean overall seed density of the soil seed bank was 13,475.3 ind m(-2). Density and the number of seeds increased initially and then decreased with increased altitude. Maximum seed density (22,500.2 ind m(-2)) was found at 165 m above sea level in the intermediately flooded riverbank, with the seed number accounting for 27.8 % of the total soil seed bank. Average seed density declined significantly with soil depth. The similarity of seed bank to standing vegetation was relatively high. DISCUSSION AND EVALUATION: The environmental heterogeneity created by the wide range and seasonal flooding led to the changes in biodiversity and seed density along altitude gradient. The seasonal flooding also led to the increase in the similarity of seed bank to standing vegetation as their composition both degraded. CONCLUSIONS: The seasonal flooding due to the dam reshape the composition and spatial distribution of riparian soil seed bank and limit the vegetation to a grassland dominated by a few annuals and perennials in the Three Gorges Reservoir Region. PMID- 27186454 TI - Proximal tibial reconstruction with auto transplantation of the fibular growth plate: two case reports, describing the surgical technique. AB - INTRODUCTION: Tumors of the proximal tibia, in children, can affect the growth plate and pose a challenge to further reconstruction of the bone defects resulting from tumor resection. Reconstruction methods do not always compensate the potential for bone growth in this segment. We present a new surgical technique of bone reconstruction, based on the transposition of the ipsilateral fibula with its growth plate and the use of an internal sliding fixation device, without need for microsurgical technique. CASE DESCRIPTION: We report two patients with osteosarcoma of the proximal tibia affecting the growth cartilage who were treated with the new technique. DISCUSSION AND EVALUATION: In both cases, bone healing, hypertrophy and longitudinal growth of the transposed fibula were documented. CONCLUSIONS: This new technique preserves the blood supply of the auto-transplanted bone segment, maintaining physeal growth potential, with no need for microsurgery. The implant allows longitudinal bone growth, which was radiographically confirmed. LEVEL OF EVIDENCE: Case report, Level IV. PMID- 27186457 TI - Solving multi-customer FPR model with quality assurance and discontinuous deliveries using a two-phase algebraic approach. AB - A multi-customer finite production rate (FPR) model with quality assurance and discontinuous delivery policy was investigated in a recent paper (Chiu et al. in J Appl Res Technol 12(1):5-13, 2014) using differential calculus approach. This study employs mathematical modeling along with a two-phase algebraic method to resolve such a specific multi-customer FPR model. As a result, the optimal replenishment lot size and number of shipments can be derived without using the differential calculus. Such a straightforward method may assist practitioners who with insufficient knowledge of calculus in learning and managing the real multi customer FPR systems more effectively. PMID- 27186458 TI - Development and application of a direct method to observe the implant/bone interface using simulated bone. AB - BACKGROUND: Primary stability after implant placement is essential for osseointegration. It is important to understand the bone/implant interface for analyzing the influence of implant design on primary stability. In this study rigid polyurethane foam is used as artificial bone to evaluate the bone-implant interface and to identify where the torque is being generated during placement. METHODS: Five implant systems-Straumann-Standard (ST), Straumann-Bone Level (BL), Straumann-Tapered Effect (TE), Nobel Biocare-Branemark MKIII (MK3), and Nobel Biocare-Branemark MKIV (MK4)-were used for this experiment. Artificial bone blocks were prepared and the implant was installed. After placement, a metal jig and one side artificial bone block were removed and then the implant embedded in the artificial bone was exposed for observing the bone-implant interface. A digital micro-analyzer was used for observing the contact interface. RESULTS: The insertion torque values were 39.35, 23.78, 12.53, 26.35, and 17.79 N cm for MK4, BL, ST, TE, and MK3, respectively. In ST, MK3, TE, MK4, and BL the white layer areas were 61 * 103 MUm(2), 37 * 103 MUm(2), 103 * 103 MUm(2) in the tapered portion and 84 * 03 MUm(2) in the parallel portion, 134 * 103 MUm(2), and 98 * 103 MUm(2) in the tapered portion and 87 * 103 MUm(2) in the parallel portion, respectively. CONCLUSIONS: The direct observation method of the implant/artificial bone interface is a simple and useful method that enables the identification of the area where implant retention occurs. A white layer at the site of stress concentration during implant placement was identified and the magnitude of the stress was quantitatively estimated. The site where the highest torque occurred was the area from the thread crest to the thread root and the under and lateral aspect of the platform. The artificial bone debris created by the self-tapping blade accumulated in both the cutting chamber and in the space between the threads and artificial bone. PMID- 27186459 TI - Aggressive re-warming at 38.5 degrees C following deep hypothermia at 21 degrees C increases neutrophil membrane bound elastase activity and pro inflammatory factor release. AB - BACKGROUND: Cardiopulmonary bypass (CPB) is often performed under hypothermic condition. The effects of hypothermia and re-warming on neutrophil activity are unclear. This study aimed to compare the effects of different hypothermia and re warming regimens on neutrophil membrane bound elastase (MBE) activity and the release of pro-inflammatory factors from neutrophils. METHODS: Human neutrophils were exposed to different hypothermia and re-warming regimens. MBE activity and the release of interleukin (IL)-beta1, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha were measured. RESULTS: Neutrophil MBE activity was significantly reduced after 60-min moderate (28 degrees C) or deep (21 degrees C) hypothermic treatment. Compared with normothermic (37 degrees C) re-warming, aggressive re warming (38.5 degrees ) for 120 min following deep hypothermia (21 degrees C) dramatically increased neutrophil MBE activity (P < 0.05). Co-incubation of neutrophils with platelet-rich plasma further increased MBE activity significantly under all the tested temperature regimens. IL-beta1 release from neutrophils was significantly higher after deep hypothermia (21 degrees C) followed by normothermic (37 degrees C) re-warming than after moderate hypothermia (28 degrees C) followed by normothermic re-warming (P < 0.05). Aggressive re-warming (38.5 degrees ) following deep hypothermia significantly increased the release of IL-beta1, IL-8, and TNF-alpha from neutrophil compared with moderate re-warming (37 degrees C) (all P < 0.05). CONCLUSION: Aggressive re-warming following deep hypothermia may contribute to CPB-associated tissue injury by increasing neutrophil MBE activity and stimulating pro-inflammatory factor release, thus, should be avoided. The optimal hypothermic temperature of CPB should be determined based on patient clinical characteristics and surgery type. PMID- 27186460 TI - Non-conductive ferromagnets based on core double-shell nanoparticles for radio electric applications. AB - Two fabrication schemes of magnetic metal-polymer nanocomposites films are described. The nanocomposites are made of graphene-coated cobalt nanoparticles embedded in a polystyrene matrix. Scheme 1 uses non-covalent chemistry while scheme 2 involves covalent bonding with radicals. Preservation of the net-moment of cobalt and electrical insulation are achieved by means of a core double-shell structure of cobalt-graphene-polystyrene. The graphene shell has two functions: it is a protective layer against metal core oxidation and it serves as the functionalization surface for polymer grafting as well. The polystyrene shell is used as an insulating layer between nanoparticles and improves nanoparticles dispersion inside the polystyrene matrix. The theoretical maximum volume filling ratio estimated at ~30 % is almost reached. The nanocomposites are shown to undergo percolation behavior but retain low conductivity (<1 S/m) at the highest filling ratio reached ~25 % leading to extremely low losses (10(-3)) at high frequency. Such low conductivity values are combined with large magnetization, as high as 0.9 T. Ability for radiofrequency applications is discussed in regards to the obtained magnetization. PMID- 27186461 TI - Postoperative effects of laparoscopic sleeve gastrectomy in morbid obese patients with type 2 diabetes. AB - BACKGROUND: Laparoscopic Sleeve Gastrectomy has become one of the most popular bariatric surgery types and helps treating not only obesity but also endocrinological diseases related to obesity. Therefore we aimed to evaluate the effects of laparoscopic sleeve gastrectomy on the treatment of type 2 diabetes. METHODS: All patients, who underwent morbid obesity surgery during 2013-2014 and had a HbA1c >6 % were included in this prospective study. Demographical data, usage of oral antidiabetic drugs or insulin were recorded, and laboratory findings as HbA1c and fasting plasma glucose were evaluated preoperatively and postoperatively at the 6th and 12th months. Diabetes remission criteria were used to assess success of the surgical treatment. RESULTS: Totally 88 patients were included in this study. 55 patients were using oral antidiabetic drugs and 33 patients were using insulin. At the 6th month complete remission was observed in 80 (90.9 %), partial remission in 3 (3.4 %) and persistent diabetes in 5 (5.6 %) patients. At the 12th month complete remission was observed in 84 (95.4 %), partial remission in 1 (1.1 %) and persistent diabetes in 3 (3.4 %) patients. CONCLUSIONS: This study indicated that laparoscopic sleeve gastrectomy surgery achieved a complete remission of diabetes in 95.4 % patients having type 2 diabetes during a 1 year fallow up period. However, complete remission of type 2 diabetes has been reported as 80 % during long term fallow up in the literature. In our opinion this rate may change with longer follow up periods and studies involving more patients suffering type 2 diabetes. PMID- 27186462 TI - Meals of differing caloric content do not alter physical activity behavior during a subsequent simulated recess period in children. AB - OBJECTIVE: Research on adults and animals has demonstrated that chronic and acute overfeeding can alter physical activity behavior. However, there are no assessments of the acute effects of high-calorie (HC) meals on physical activity behavior in children. This is of importance as a typical school lunch is HC. If this type of meal negatively impacts subsequent physical activity behavior, the ability of post-lunch recess periods as a means to increase energy expenditure may be lessened. PURPOSE: To assess the effect of two meals of differing caloric content, HC and low calorie (LC), on children's subsequent physical activity behavior. METHODS: Nineteen healthy children (aged 6-10) completed two laboratory sessions where they were fed lunch with HC or LC content, but equivalent macronutrient distribution. Children had 15 min to consume as much of the meal as possible per session. Children consumed 659.5 +/- 101.3 kcal in the HC condition and 291.8 +/- 12.1 kcal in the LC condition. After the meal, children went to a gymnasium for 40 min. In the gymnasium children had free-choice access to obstacle courses, various sports equipment, and a table with sedentary activities. Children could play with any of the activities in any amount they wished for the entire activity session. Children's physical activity was monitored with accelerometers and that data was converted into caloric expenditure. Each child ate all meals and participated in the free-choice activity sessions with no other children present. RESULTS: Caloric expenditure during the free-choice activity sessions was not significantly different (p = 0.4) between the HC (89.2 +/- 27.3 kcals) and LC (83.4 +/- 34.9 kcals) conditions. However, caloric balance (kcals eaten-kcals expended) was 2.74-fold greater (p < 0.001) in the HC condition (Delta 570.3 +/- 92.2 kcals) than the LC condition (Delta 208.4 +/- 32.0 kcals). CONCLUSION: Children did not alter their physical activity behavior during a free-choice activity session after consuming a HC meal versus a LC meal. Because activity was not different across the two conditions, children had a much greater caloric surplus during the HC condition than the LC condition. PMID- 27186463 TI - Impact of urban contamination of the La Paz River basin on thermotolerant coliform density and occurrence of multiple antibiotic resistant enteric pathogens in river water, irrigated soil and fresh vegetables. AB - La Paz River in Andean highlands is heavily polluted with urban run-off and further contaminates agricultural lowlands and downstream waters at the Amazon watershed. Agricultural produce at this region is the main source of vegetables for the major Andean cities of La Paz and El Alto. We conducted a 1 year study, to evaluate microbial quality parameters and occurrence of multiple enteropathogenic bacteria (Enterohemorrhagic E. coli-EHEC, Enteroinvasive E. coli or Shigella-EIEC/Shigella, Enteroaggregative E. coli-EAEC, Enteropathogenic E. coli-EPEC Enterotoxigenic E. coli-ETEC and Salmonella) and its resistance to 11 antibiotics. Four sampling locations were selected: a fresh mountain water reservoir (un-impacted, site 1) and downstream sites receiving wastewater discharges (impacted, sites 2-4). River water (sites 1-4, N = 48), and soil and vegetable samples (site 3, N = 24) were collected during dry (April-September) and rainy seasons (October-March). Throughout the study, thermotolerant coliform density values at impacted sites greatly exceeded the guidelines for recreational and agricultural water uses. Seasonal differences were found for thermotolerant coliform density during dry season in water samples nearby a populated and hospital compound area. In contrast to the un-impacted site, where none of the tested enteropathogens were found, 100 % of surface water, 83 % of soil and 67 % of vegetable samples at impacted sites, were contaminated with at least one enteropathogen, being ETEC and Salmonella the most frequently found. ETEC isolates displayed different patterns of toxin genes among sites. The occurrence of enteropathogens was associated with the thermotolerant coliform density. At impacted sites, multiple enteropathogens were frequently found during rainy season. Among isolated enteropathogens, 50 % were resistant to at least two antibiotics, with resistance to ampicillin, nalidixic acid, trimethoprim sulfamethoxazole and tetracycline commonly present. Moreover, some Salmonella isolates were distinguished by their multi-resistance to >=8 antibiotics, within soil and vegetable samples. Overall, this study demonstrates that La Paz River-an affluent of the Amazon macrobasin-is heavily polluted along the year with a high density of thermotolerant coliforms and is a reservoir of multiple antibiotic resistant enteropathogens, present in river water, soil and vegetables. These data highlight health risk associated with food and waterborne diseases at the region. PMID- 27186464 TI - On meeting capital requirements with a chance-constrained optimization model. AB - This paper deals with a capital to risk asset ratio chance-constrained optimization model in the presence of loans, treasury bill, fixed assets and non interest earning assets. To model the dynamics of loans, we introduce a modified CreditMetrics approach. This leads to development of a deterministic convex counterpart of capital to risk asset ratio chance constraint. We pursue the scope of analyzing our model under the worst-case scenario i.e. loan default. The theoretical model is analyzed by applying numerical procedures, in order to administer valuable insights from a financial outlook. Our results suggest that, our capital to risk asset ratio chance-constrained optimization model guarantees banks of meeting capital requirements of Basel III with a likelihood of 95 % irrespective of changes in future market value of assets. PMID- 27186465 TI - Comparison of fuzzy AHP and fuzzy TODIM methods for landfill location selection. AB - Landfill location selection is a multi-criteria decision problem and has a strategic importance for many regions. The conventional methods for landfill location selection are insufficient in dealing with the vague or imprecise nature of linguistic assessment. To resolve this problem, fuzzy multi-criteria decision making methods are proposed. The aim of this paper is to use fuzzy TODIM (the acronym for Interactive and Multi-criteria Decision Making in Portuguese) and the fuzzy analytic hierarchy process (AHP) methods for the selection of landfill location. The proposed methods have been applied to a landfill location selection problem in the region of Casablanca, Morocco. After determining the criteria affecting the landfill location decisions, fuzzy TODIM and fuzzy AHP methods are applied to the problem and results are presented. The comparisons of these two methods are also discussed. PMID- 27186466 TI - An efficient method for tracking a magnetic target using scalar magnetometer array. AB - The position of a magnetic target can be obtained through magnetic anomaly which is measured by a magnetic sensor. Comparing with vector magnetic sensor, the measurement value of the scalar magnetic sensor is almost not influenced by its orientation in measurement coordinate axes. Therefore, scalar magnetic sensors can be easily assembled into an array. Based on analysis of the total scalar magnetic anomaly measured by scalar magnetometer, we present an efficient method for tracking a magnetic target using scalar magnetometer array. In this method, we separate the position information and magnetic moment information of magnetic target by matrix transformation. Then, we can obtain the position of the magnetic target in real time by a scalar magnetometer array and a particle swarm optimization algorithm. In addition, the magnetic moment of the target can be estimated when the target's position had been calculated. The simulation shows that the position of the target can be calculated accurately and the relative error of the position is <5 %. The calculated magnetic moment of the target is close to the theoretical value. In addition, execution time of each calculation is <1 s. Thus, the position of the magnetic target can be obtained in real-time through this method. PMID- 27186467 TI - Growth characteristics of freeze-tolerant baker's yeast Saccharomyces cerevisiae AFY in aerobic batch culture. AB - Saccharomyces cerevisiae AFY is a novel baker's yeast strain with strong freeze tolerance, and can be used for frozen-dough processing. The present study armed to clarify the growth characteristics of the yeast AFY. Aerobic batch culture experiments of yeast AFY were carried out using media with various initial glucose concentrations, and the culture process was analyzed kinetically. The growth of the yeast AFY exhibited a diauxic pattern with the first growth stage consuming glucose and the second growth stage consuming ethanol. The cell yield decreased with increasing initial glucose concentration in the first growth stage, and also decreased with increasing initial ethanol concentration in the second growth stage. In the initial glucose concentration range of 5.0-40.0 g/L, the simultaneous equations of Monod equation, Luedeking-Piret equation and pseudo Luedeking-Piret equation could be used to describe the concentrations of cell, ethanol and glucose in either of the two exponential growth phases. At the initial glucose concentrations of 5.0, 10.0 and 40.0 g/L, the first exponential growth phase had a maximal specific cell growth rate of 0.52, 0.98 and 0.99 h( 1), while the second exponential growth phase had a maximal specific cell growth rate of 0.11, 0.06 and 0.07 h(-1), respectively. It was indicated that the efficiency of the yeast production could be improved by reducing the ethanol production in the first growth stage. PMID- 27186468 TI - Dynamic mechanical response and a constitutive model of Fe-based high temperature alloy at high temperatures and strain rates. AB - The effects of strain rate and temperature on the dynamic behavior of Fe-based high temperature alloy was studied. The strain rates were 0.001-12,000 s(-1), at temperatures ranging from room temperature to 800 degrees C. A phenomenological constitutive model (Power-Law constitutive model) was proposed considering adiabatic temperature rise and accurate material thermal physical properties. During which, the effects of the specific heat capacity on the adiabatic temperature rise was studied. The constitutive model was verified to be accurate by comparison between predicted and experimental results. PMID- 27186469 TI - Effects of weather conditions, light conditions, and road lighting on vehicle speed. AB - Light conditions are known to affect the number of vehicle accidents and fatalities but the relationship between light conditions and vehicle speed is not fully understood. This study examined whether vehicle speed on roads is higher in daylight and under road lighting than in darkness, and determined the combined effects of light conditions, posted speed limit and weather conditions on driving speed. The vehicle speed of passenger cars in different light conditions (daylight, twilight, darkness, artificial light) and different weather conditions (clear weather, rain, snow) was determined using traffic and weather data collected on an hourly basis for approximately 2 years (1 September 2012-31 May 2014) at 25 locations in Sweden (17 with road lighting and eight without). In total, the data included almost 60 million vehicle passes. The data were cleaned by removing June, July, and August, which have different traffic patterns than the rest of the year. Only data from the periods 10:00 A.M.-04:00 P.M. and 06:00 P.M.-10:00 P.M. were used, to remove traffic during rush hour and at night. Multivariate adaptive regression splines was used to evaluate the overall influence of independent variables on vehicle speed and nonparametric statistical testing was applied to test for speed differences between dark-daylight, dark twilight, and twilight-daylight, on roads with and without road lighting. The results show that vehicle speed in general depends on several independent variables. Analyses of vehicle speed and speed differences between daylight, twilight and darkness, with and without road lighting, did not reveal any differences attributable to light conditions. However, vehicle speed decreased due to rain or snow and the decrease was higher on roads without road lighting than on roads with lighting. These results suggest that the strong association between traffic accidents and darkness or low light conditions could be explained by drivers failing to adjust their speed to the reduced visibility in dark conditions. PMID- 27186470 TI - Timing of carbohydrate ingestion did not affect inflammatory response and exercise performance during prolonged intermittent running. AB - BACKGROUND: Carbohydrate ingestion during exercise is known to attenuate exercise induced elevation of plasma IL-6 concentration. However, the influence of timing of carbohydrate ingestion remains unclear. PURPOSE: The present study investigated the influence of different timing of carbohydrate ingestion during a simulated soccer game on exercise performance, metabolic and inflammatory responses. METHODS: Seven active males performed 3 exercise trials in a randomized order. The exercise consisted of two consecutive bouts of 45 min running (4-16 km/h), separated with 15 min rest period between bouts. The subjects ingested carbohydrate gel (1.0 g/kg) immediately before the first bout of exercise (ONE), immediately before first and second bouts of exercise (0.5 g/kg for each ingestion) (TWO) or placebo immediately before exercise (PLA) Time course changes of maximal jump height, peak power output during 6-s maximal pedaling, perceived fatigue and heart rate (HR) were monitored. Blood samples were also drawn to determine blood glucose, serum insulin, free fatty acid (FFA), myoglobin (Mb), creatine kinase (CK) and plasma IL-6 concentrations. RESULTS: Blood glucose and serum insulin concentrations were significantly higher in the ONE trial after first bout of 45 min exercise compared with PLA trial (P < 0.05), while serum FFA concentration was significantly elevated in PLA compared with ONE and TWO trials after second bout of exercise (P < 0.05). However, changes of jump height, peak power output during 6-s maximal pedaling, perceived fatigue, HR, or indirect muscle damage (Mb, CK) and inflammatory (IL-6) markers were not significantly different among three trials (P > 0.05). CONCLUSIONS: The timing of carbohydrate ingestion did not affect exercise performance, exercise-induced muscle damage or inflammatory response during a simulated soccer game. PMID- 27186471 TI - Hybrid model for analysis of abnormalities in diabetic cardiomyopathy and diabetic retinopathy related images. AB - At present image processing methods hold a noteworthy position in unravelling various medical imaging challenges. The high risk disorders such as diabetic cardiomyopathy and diabetic retinopathy are considered as applications for proposed method. The dictum of this paper is on observing enhancement and segmentation of the cross sectional view of a blood capillary of a right coronary artery image of a diabetic patient and also retinal images. A hybrid model using hybrid morphological reconstruction technique as pre-processing with watershed segmentation method as post-processing is developed in this work. PMID- 27186472 TI - A comprehensive survey of the relationship between self-efficacy and performance for the governmental auditors. AB - As governmental auditing is involved in evaluating the legitimacy, economy, efficiency, and effectiveness of how the various administrative branches use their allocated resources to optimize the government's functions, it is expected that the performance of the auditors in charge are strongly influenced by their respective qualities such as self-efficacy and experience, etc. To further understand the factors that may enhance their performance and to ultimately provide practical recommendations for the audit authorities, we have surveyed about 50 % of all the governmental auditors in Taiwan. The result showed that any auditing experience and professionalization do positively influence the professional awareness, and acquired knowledge and skillset of an auditor can effectively improve his or her professional judgment. We also found that perceived ability, problem-solving skills, and resource sharing may significantly impact any performance involved. Our study provides a workable management guidelines for strengthening the self-efficacy of audit authorities in Taiwan. PMID- 27186473 TI - Obstacle avoidance planning of space manipulator end-effector based on improved ant colony algorithm. AB - With the development of aerospace engineering, the space on-orbit servicing has been brought more attention to many scholars. Obstacle avoidance planning of space manipulator end-effector also attracts increasing attention. This problem is complex due to the existence of obstacles. Therefore, it is essential to avoid obstacles in order to improve planning of space manipulator end-effector. In this paper, we proposed an improved ant colony algorithm to solve this problem, which is effective and simple. Firstly, the models were established respectively, including the kinematic model of space manipulator and expression of valid path in space environment. Secondly, we described an improved ant colony algorithm in detail, which can avoid trapping into local optimum. The search strategy, transfer rules, and pheromone update methods were all adjusted. Finally, the improved ant colony algorithm was compared with the classic ant colony algorithm through the experiments. The simulation results verify the correctness and effectiveness of the proposed algorithm. PMID- 27186474 TI - Biological screening of selected Pacific Northwest forest plants using the brine shrimp (Artemia salina) toxicity bioassay. AB - The brine shrimp (Artemia salina) bioassay was used to screen 211 methanol extracts from 128 species of Pacific Northwest plants in search of general cytotoxic activity. Strong toxicity (LC50 < 100 ug/ml) was found for 17 extracts from 13 species, with highest activity observed for Angelica arguta roots at <10 ug/ml. Notably, four species of cedar trees and one of juniper in the family Cupressaceae dominated this group with LC50 for heartwood extracts ranging from 15 to 89 ug/ml. Moderate toxicity (LC50 100-500 ug/ml) was found in 38 extracts from 27 species, while weak toxicity (LC50 500-1000 ug/ml) was detected for 17 extracts in 16 species. There were 139 extracts from 99 species that were non toxic (LC50 > 1000 ug/ml). Our subsequent studies of conifer heartwoods with strong activity confirm the assay's value for identifying new investigational leads for materials with insecticidal and fungicidal activity. PMID- 27186476 TI - Clinical utility of high-flow nasal cannula oxygen therapy for acute respiratory failure in patients with hematological disease. AB - A high-flow nasal cannula (HFNC) is a newly developed device that enables high flow oxygen therapy for patients with serious cardiopulmonary problems, but there are few data regarding its use in patients with hematological disease. The efficacy and tolerability of HFNCs for patients who developed ARF during the treatment of various hematological diseases was evaluated. Fifty-six patients underwent HFNC therapy during the last 2 years, and the causes of ARF were mainly pneumonia (n = 37) or acute congestive heart failure (n = 7). Only 11 patients (20 %) showed a good response to HFNC therapy, and remaining 45 patients (80 %) failed to respond to the initial HFNC therapy and, therefore, underwent second line therapy including endotracheal intubation with mechanical ventilation (n = 15), non-invasive positive pressure ventilation (n = 1), or narcotic palliation alone (n = 29). Thus, HFNC appear not to be a viable treatment option in 4 out of 5 patients in this cohort of patients with hematological disease, but it was well tolerated in most patients (96 %); no major complications except for nasal soreness (n = 2) were observed. Multivariate analysis showed that the cause of ARF (pneumonia, odds ratio 11.2, 95 % CI 1.76-71.5, p = 0.01) was the only risk factor for treatment failure. PMID- 27186477 TI - Solution of the Falkner-Skan wedge flow by a revised optimal homotopy asymptotic method. AB - In this paper, a revised optimal homotopy asymptotic method (OHAM) is applied to derive an explicit analytical solution of the Falkner-Skan wedge flow problem. The comparisons between the present study with the numerical solutions using (fourth order Runge-Kutta) scheme and with analytical solution using HPM-Pade of order [4/4] and order [13/13] show that the revised form of OHAM is an extremely effective analytical technique. PMID- 27186475 TI - Functional characterization of Rorippa indica defensin and its efficacy against Lipaphis erysimi. AB - Rorippa indica, a wild crucifer, has been previously reported as the first identified plant in the germplasm of Brassicaceae known to be tolerant towards the mustard aphid Lipaphis erysimi Kaltenbach. We herein report the full-length cloning, expression, purification and characterization of a novel R. indica defensin (RiD) and its efficacy against L. erysimi. Structural analysis through homology modeling of RiD showed longer alpha-helix and 3rd beta-sheet as compared to Brassica juncea defensin (BjD). Recombinant RiD and BjD was purified for studying its efficacy against L. erysimi. In the artificial diet based insect bioassay, the LC50 value of RiD against L. erysimi was found to be 9.099 +/- 0.621 ug/mL which is far lower than that of BjD (43.51 +/- 0.526 ug/mL). This indicates the possibility of RiD having different interacting partner and having better efficacy against L. erysimi over BjD. In the transient localization studies, RiD signal peptide directed the RiD: yellow fluorescent protein (YFP) fusion protein to the apoplastic regions which indicates that it might play a very important role in inhibiting nutrient uptake by aphids which follow mainly extracellular route to pierce through the cells. Hence, the present study has a significant implication for the future pest management program of B. juncea through the development of aphid tolerant transgenic plants. PMID- 27186478 TI - Inference of biological networks using Bi-directional Random Forest Granger causality. AB - The standard ordinary least squares based Granger causality is one of the widely used methods for detecting causal interactions between time series data. However, recent developments in technology limit the utilization of some existing implementations due to the availability of high dimensional data. In this paper, we are proposing a technique called Bi-directional Random Forest Granger causality. This technique uses the random forest regularization together with the idea of reusing the time series data by reversing the time stamp to extract more causal information. We have demonstrated the effectiveness of our proposed method by applying it to simulated data and then applied it to two real biological datasets, i.e., fMRI and HeLa cell. fMRI data was used to map brain network involved in deductive reasoning while HeLa cell dataset was used to map gene network involved in cancer. PMID- 27186479 TI - A case of pacemaker implantation in the patient with duplication of the left innominate vein: a case report. AB - INTRODUCTION: Duplication of the left innominate vein is a rare systemic venous anomaly defined as the coexistence of a retroaortic innominate vein and a normally positioned left innominate vein. We describe a successful case of pacemaker implantation in a patient with duplication of the left innominate vein via a retroaortic innominate vein. CASE DESCRIPTION: A 70-year-old mentally challenged man was admitted to our hospital because of bradycardia and an altered state of consciousness. Electrocardiogram indicated sinus arrest and junctional escape rhythm with a heart rate of 40 beats/min; hence, a pacemaker was implanted. Left subclavian venography showed two vessels that were connected to the superior vena cava: a narrow, normal positioned left innominate vein and a tortuous vein. The normally positioned left innominate vein was too narrow to pass through with a guide wire. Therefore, we chose the tortuous vein for implantation. However, the procedure was difficult because of the vein's tortuosity. Finally, leads at the right atrium and ventricle were successfully implanted using a steerable stylet. After the procedure, computed tomography showed two innominate veins: a retroaortic innominate vein and narrow left innominate vein that was a duplication of the left innominate vein. DISCUSSION AND EVALUATION: The exact embryogenesis of retroaortic innominate vein remains unknown and incidence of retroaortic innominate vein is very rare. But for cardiologists performing transvenous pacemaker insertion, the anomalous brachiocephalic vein may cause technical difficulty during a left arm approach. CONCLUSIONS: In cases in which subclavian venography shows a tortuous vein, cardiologists should consider the presence of a retroaortic innominate vein. PMID- 27186480 TI - Spatially and temporally continuous LAI datasets based on the mixed pixel decomposition method. AB - The leaf area index (LAI) is a key biophysical parameter that determines the state of plant growth. A global LAI has been routinely produced by the Moderate Resolution Imaging Spectro-radiometer (MODIS) and Advanced Very High Resolution Radiometer (AVHRR). However, the MODIS and AVHRR LAI products cannot be synchronized with the same spatial and temporal resolution. The LAI features are not discernible when a global LAI product is implemented at the regional scale because it has low resolution and different land cover types. To obtain high spatial and temporal resolution of LAI products, an empirical model based on the pixel scale was developed. The approach to generate a long (multi-decade) time series of a 1-km spatial resolution LAI normally integrates both AVHRR and MODIS datasets for different land cover types. In this paper, a regression-based model for generating a vegetation LAI was developed using the AVHRR Global Inventory Modelling and Mapping Studies Normalized Difference Vegetation Index (NDVI), MODIS LAI and land cover as input data; the model was evaluated by using relevant data from the same period data from 2000 to 2006. The results of this method show a good consistency in LAI values retrieved from the AVHRR NDVI and MODIS LAI. This simple method has no specific-limited data requirements and can provide improved spatial and temporal resolution in a region without ground data. PMID- 27186481 TI - An algorithm for space-time block code classification using higher-order statistics (HOS). AB - This paper proposes a novel algorithm for space-time block code classification, when a single antenna is employed at the receiver. The algorithm exploits the discriminating features provided by the higher-order cumulants of the received signal. It does not require estimation of channel and information of the noise. Computer simulations are conducted to evaluate the performance of the proposed algorithm. The results show the performance of the algorithm is good. PMID- 27186484 TI - A multivariate morphometric investigation to delineate stock structure of gangetic whiting, Sillaginopsis panijus (Teleostei: Sillaginidae). AB - This study was conducted to delineate the stock structure of Sillaginopsis paniijus based on morphometric characters of the species. A total of 194 specimens were collected from the Meghna, Tentulia and Baleswar rivers located in the southern coastal zone of Bangladesh. Data were subjected to univariate ANOVA, multivariate ANOVA, discriminate function analysis (DFA), and principal component analysis. Mean variations of ten morphometric characters; HD, HBD, LBD, PsOL, ED, SnL, SPrDL, HAF, LSDB and LPB showed significant differences (p < 0.05) among 27 morphometric traits that were selected for the study. In DFA, the overall assignments of individuals into their correctly classified original groups were 71.1 and 70.6 % for male and female, respectively. A scatter plot of the first two discriminant functions was used to visually depict the discrimination among the populations. The results showed different stocks of S. panijus in the rivers of Baleswar, Tentulia and Meghna in southwest coast of Bangladesh. PMID- 27186482 TI - Simeprevir with peginterferon/ribavirin for patients with hepatitis C virus genotype 1: high frequency of viral relapse in elderly patients. AB - PURPOSE: The tolerability and efficacy of simeprevir in combination with peginterferon and ribavirin in patients infected with hepatitis C virus (HCV) genotype 1 under actual clinical conditions were investigated. METHODS: A total of 176 patients with chronic HCV genotype 1 infection were treated with simeprevir for 12 weeks plus Peg-IFN/RBV for 24 weeks. Overall, 107 (60.7 %) patients were aged 60 years or more, and 16 (9 %) patients were aged 70 years or more. Treatment discontinuation, sustained virological response 12 (SVR12), and viral relapse were evaluated and compared between younger patients and elderly patients. RESULTS: The rates of undetectable HCV RNA at the end of treatment were 95.8, 100 and 93.1 % in treatment-naive, prior relapse, and prior non-responders, respectively. However, the rates of SVR12 were 82.4, 88.2 and 69.2 %, respectively. Especially in prior non-responders, viral relapse was relatively frequent. Treatment discontinuation and SVR12 were not different between patients aged <70 and >=70 years, but viral relapse after completing treatment was significantly more frequent in patients aged >=70 years (p = 0.012). CONCLUSIONS: In simeprevir with peginterferon and ribavirin therapy, viral relapse was relatively frequent. Especially in elderly patients, the relapse rate was high after completing treatment, instead of low frequency of discontinuation by the adverse events. PMID- 27186485 TI - Integral inequalities under beta function and preinvex type functions. AB - In the present paper, the notion of P-preinvex function is introduced and new integral inequalities for this kind of function along with beta function are establised. The work extends the results appeared in the literature. PMID- 27186487 TI - Multimodal game bot detection using user behavioral characteristics. AB - As the online service industry has continued to grow, illegal activities in the online world have drastically increased and become more diverse. Most illegal activities occur continuously because cyber assets, such as game items and cyber money in online games, can be monetized into real currency. The aim of this study is to detect game bots in a massively multiplayer online role playing game (MMORPG). We observed the behavioral characteristics of game bots and found that they execute repetitive tasks associated with gold farming and real money trading. We propose a game bot detection method based on user behavioral characteristics. The method of this paper was applied to real data provided by a major MMORPG company. Detection accuracy rate increased to 96.06 % on the banned account list. PMID- 27186483 TI - Amino acid composition in eyes from zebrafish (Danio rerio) and sardine (Sardina pilchardus) at the larval stage. AB - A comparative study was performed to identify differences in the amino acid composition of the eyes from zebrafish (Danio rerio) and sardine (Sardina pilchardus) larvae and their link to the environmental adaption of the species. Amino acids in the acidic hydrolysates of eyes from 11 zebrafish and 12 sardine were determined with the use of high-performance liquid chromatography involving precolumn derivatization with ortho-phthalaldehyde. Differences in the content of most amino acids were detected between zebrafish and sardine. These amino acids were aspartate, glutamate, serine, glycine, threonine, arginine, methionine, valine, phenylalanine, isoleucine, leucine and lysine. Of particular note, the percentage of methionine in zebrafish eyes was much higher than that in sardine, whereas the opposite was observed for glutamate and glycine. These results indicate that zebrafish and sardine likely have experienced differences in adaptation to environmental changes. We suggest that the amino acid composition of eyes represents a powerful tool to discriminate between species characterized by different lifestyle and inhabiting different environments. PMID- 27186486 TI - Oestrogens and oestrogen receptors in prostate cancer. AB - The role of androgens in prostate cancer is obvious due to the fact that androgen signalling is the main regulator of prostate growth and function. Androgen deprivation therapy is a mainstay treatment for advanced prostate cancer. However, prostate cancer often becomes androgen-independent, which in consequence leads to lethal and incurable disease. In addition, oestrogens play a crucial role in prostate cancer, especially in elder men in whom the overall ratio of oestrogens to androgens is increasing. This review summarizes the current knowledge on molecular mechanisms through which oestrogens are involved in prostate cancer development. We focused on commonly alternated molecular signalling pathways contributing to tumourgenesis in prostate cancer. PMID- 27186488 TI - Hermite-Hadamard type inequalities for n-times differentiable and geometrically quasi-convex functions. AB - By Holder's integral inequality, the authors establish some Hermite-Hadamard type integral inequalities for n-times differentiable and geometrically quasi-convex functions. PMID- 27186489 TI - A novel family VIII carboxylesterase hydrolysing third- and fourth-generation cephalosporins. AB - A metagenomic library was constructed from a soil sample of spindle tree rhizosphere. From this library, one clone with esterase activity was selected. The sequence analysis revealed an open reading frame (EstSTR1) encoded protein of 390 amino acids. EstSTR1 is a family VIII carboxylesterase and retains the S-X-X K motif conserved in both family VIII carboxylesterases and class C beta lactamases. The estSTR1 gene was overexpressed in E. coli and the recombinant protein was purified by purified by metal chelating affinity chromatography and size-exclusion chromatography. EstSTR1 hydrolysed p-nitrophenyl esters, exhibited the highest activity toward p-nitrophenyl butyrate. Furthermore, EstSTR1 could hydrolyse third- and fourth-generation cephalosporins (cefotaxime and cefepime) as well as first-generation cephalosporin (cephalothin). Site-directed mutagenesis studies revealed that a catalytic residue, Ser71, of EstSTR1 plays an essential role in hydrolysing both antibiotics and p-nitrophenyl esters. We demonstrate that a metagenome-derived carboxylesterase displays beta-lactam hydrolysing activities toward third- and fourth-generation cephalosporins. PMID- 27186491 TI - Development of the safety control framework for shield tunneling in close proximity to the operational subway tunnels: case studies in mainland China. AB - INTRODUCTION: China's largest cities like Beijing and Shanghai have seen a sharp increase in subway network development as a result of the rapid urbanization in the last decade. The cities are still expanding their subway networks now, and many shield tunnels are being or will be constructed in close proximity to the existing operational subway tunnels. The execution plans for the new nearby shield tunnel construction calls for the development of a safety control framework-a set of control standards and best practices to help organizations manage the risks involved. CASE DESCRIPTION: Typical case studies and relevant key technical parameters are presented with a view to presenting the resulting safety control framework. The framework, created through collaboration among the relevant parties, addresses and manages the risks in a systematic way based on actual conditions of each tunnel crossing construction. The framework consists of six parts: (1) inspecting the operational subway tunnels; (2) deciding allowed movements of the existing tunnels and tracks; (3) simulating effects of the shield tunneling on the existing tunnels; (4) doing preparation work; (5) monitoring design and information management; and (6) measures and activation mechanism of the countermeasures. The six components are explained and demonstrated in detail. DISCUSSION AND EVALUATION: In the end, discussions made involve construction and post-construction settlement of the operational tunnel, application of the remedial grouting to rectify excessive settlements of the operational tunnel, and use of the innovative tool of the optical fiber measurement for tunnel movement monitoring. CONCLUSIONS: It is concluded that the construction movement of the tunnel can be controlled within 15 mm when the shield machine is <7 m in excavation diameter. The post-construction settlement of the tunnel buried in the very soft ground is much greater than its construction settlement, and last several years until reaching a final stable state. Two cases are outlined to demonstrate the feasibility of using the remedial grouting to reduce the long-term settlement of the operational tunnels. The more and more segmental tunnels being constructed, there is an increasing need of the optical fiber measurement for tunnel movement monitoring in the near future. PMID- 27186490 TI - A meta-analysis of MMP-9 promoter -1562 C/T polymorphism on susceptibility of chronic periodontitis. AB - BACKGROUND: Although many studies have focused on the association of the MMP-9 promoter -1562 C/T polymorphism with the susceptibility and/or severity of chronic periodontitis (CP), results have been inconsistent. Therefore, a meta analysis of all eligible studies was performed to derive a more precise estimation of the association between this polymorphism and CP risk. METHODS: All relevant studies were identified through a database search in PubMed, Medline, and Web of Science. All the full-text studies with appropriate analytical design, published in English, which evaluated the association of MMP-9 promoter -1562C/T polymorphism with CP risk using validated genotyping methods, and with non duplicated data were selected for this study. A fixed-effect model was used to calculate pooled ORs in the absence of heterogeneity across included trials (P > 0.1 and I(2) < 50 %), otherwise the random-effect model was applied. RESULTS: In an overall meta-analysis, pooled ORs revealed that T variant in the MMP-9 promoter -1562 C/T polymorphism was associated with a significantly decreased risk for CP under all comparison models. In subgroup analyses by ethnicity, pooled ORs showed that a significant association of the MMP-9 promoter -1562 C/T polymorphism with CP risk was only detected in Caucasians and Asians but not in mixed population. In the subgroup analysis by severity of CP, pooled ORs indicated that T allele of the MMP-9 promoter -1562 C/T polymorphism was associated with decreased susceptibility to severe CP while there was no significant association between this polymorphism and moderate CP. CONCLUSIONS: Our meta-analysis showed that T allele in the MMP-9 promoter -1562 C/T polymorphism might be a protective factor for CP, especially in Caucasians and Asians. Moreover, there was a significant association of the MMP-9 promoter -1562 C/T polymorphism with decreased susceptibility to severe CP, while the allelic and/or genotype distributions of this polymorphism were not associated with moderate CP. PMID- 27186492 TI - Building an associative classifier with multiple minimum supports. AB - Classification is one of the most important technologies used in data mining. Researchers have recently proposed several classification techniques based on the concept of association rules (also known as CBA-based methods). Experimental evaluations on these studies show that in average the CBA-based approaches can yield higher accuracy than some of conventional classification methods. However, conventional CBA-based methods adopt a single threshold of minimum support for all items, resulting in the rare item problem. In other words, the classification rules will only contain frequent items if minimum support (minsup) is set as high or any combinations of items are discovered as frequent if minsup is set as low. To solve this problem, this paper proposes a novel CBA-based method called MMSCBA, which considers the concept of multiple minimum supports (MMSs). Based on MMSs, different classification rules appear in the corresponding minsups. Several experiments were conducted with six real-world datasets selected from the UCI Machine Learning Repository. The results show that MMSCBA achieves higher accuracy than conventional CBA methods, especially when the dataset contains rare items. PMID- 27186493 TI - Two dimensional analysis of low pressure flows in the annulus region between two concentric cylinders. AB - A numerical simulation of the steady two-dimensional laminar natural convection heat transfer for the gaseous low-pressure flows in the annulus region between two concentric horizontal cylinders is carried out. This type of flow occurs in "evacuated" solar collectors and in the receivers of the solar parabolic trough collectors. A finite volume code is used to solve the coupled set of governing equations. Boussinesq approximation is utilized to model the buoyancy effect. A correlation for the thermal conductivity ratio (k r = k eff/k) in terms of Knudsen number and the modified Rayleigh number is proposed for Prandtl number (Pr = 0.701). It is found that as Knudsen number increases then the thermal conductivity ratio decreases for a given Rayleigh number. Also, it is shown that the thermal conductivity ratio k r increases as Rayleigh number increases. It appears that there is no consistent trend for varying the dimensionless gap spacing between the inner and the outer cylinder ([Formula: see text]) on the thermal conductivity ratio (k r) for the considered spacing range. PMID- 27186494 TI - A comparative study in fixation methods of medial malleolus fractures between tension bands wiring and screw fixation. AB - OBJECTIVES: The aim of this study is to compare two methods of internal fixations of fractured medial malleolus which are simple screw fixation and tension band wiring. PATIENTS AND METHODS: Over 5 years we grouped 20 patients with fractured medial malleolus into two groups of operative treatments, group1 treated by malleolar screw fixation and group2 by tension band wiring. The patients were with same age group, gender, fracture type, and etiology. We use statistical analysis for make a comparative study between the two ways of surgical treatment. RESULTS: The mean time for radiologic bone union was 11.8 weeks in group1 patients and 9.4 weeks in group2 patients (P = 0.03). No patients had any sign of fixation failure or Kirschner wires migration. According to the modified ankle scoring system of Olerud and Molander, excellent and good results were achieved in 80 % in group1 patients and 90 % in group2 patients (P = 0.049). CONCLUSIONS: Tension-band wiring may be better treatment option for internal fixation of medial malleolar fractures than screw fixation. RECOMMENDATIONS: From these findings we recommend a further randomized clinical trial of larger number of cases and longer follow-up duration in order to regard tension-band wiring a better operative option for fixation of medial malleolar fractures. PMID- 27186495 TI - Circulating DNA addresses cancer monitoring in non small cell lung cancer patients for detection and capturing the dynamic changes of the disease. AB - PURPOSE: Monitoring of key markers for lung cancer detection and tracking of acquired drug resistance is critical for the management of the disease. We aim to ascertain the value of monitoring both total cell free DNA concentrations and mutant EGFR DNA content within diverse groups of individuals most vulnerable to the disease. METHODS: We proposed longitudinal monitoring of circulating DNA using digital PCR. Circulating DNA present in peripheral blood can be obtained non-invasively and provide timely disease status update. 25 heavy smokers and 50 patients undergoing TKI therapy were recruited. Peripheral blood specimens were taken at different time points and their circulating DNA were analyzed and quantified. RESULTS: Significant higher concentrations of total cell free DNA were detected when compared with healthy high-risk individuals. Levels were stable throughout the treatment cycles, which makes it potentially a useful tool for patient stratification. Concurrent mutant T790M DNA detection of lung cancer patients at baseline achieved 82 % concordance with matched tissue analysis. Samples initially negative for the T790M gene mutation that became positive during treatment were corroborated with a repeat biopsy. The results showed its usefulness for serial monitoring. CONCLUSION: Monitoring of circulating DNA addresses the need for disease detection and shows the ability to capture the dynamic changes of the disease. PMID- 27186496 TI - Maternal diabetes impairs oxidative and inflammatory response in murine placenta. AB - Placenta is the major exchange surface between mother and fetus and plays a pivotal role in fetal development. A better understanding of the mechanisms by which diabetes alters placental function may allow better management of diabetes pregnancies. In this study, we attempt to investigate the effect of diabetic milieu with and without malformation on placental function. In order to investigate the impact of diabetic pregnancy on oxidative stress, endothelial and vascular functions of placental tissue, we mated diabetic and non-diabetic female rats with normal male rats. At gestational day 17, we terminated pregnancy, assessed fetuses for malformations and isolated placenta for measurement of various parameters of placental function. Our results show that maternal diabetes induced a state of oxidative stress in placenta, which disrupts normal signaling, activating apoptosis, as well as perturbing endothelial and vascular placental functions. The coalescence of these insults on various levels of placental function could contribute to the pleiotropic nature of diabetes-induced placental stress. PMID- 27186497 TI - Mitigation of acrylamide by l-asparaginase from Bacillus subtilis KDPS1 and analysis of degradation products by HPLC and HPTLC. AB - The use of bacterial l-asparaginase (LA) is one of the alternative approaches for acrylamide reduction in food stuffs as it catalyzes the conversion of l asparagine to l-aspartic acid and ammonia. In present investigation, purification of extracellular LA from isolate of Bacillus subtilis sp. strain KDPS-1 was carried out by solid state fermentation process. The effects of solid substrates, initial moisture content, moistening agents, temperature, and incubation time on LA production was studied, and the highest asparaginase activity (47 IU/ml) was achieved in the medium having orange peel as substrate. The enzyme was purified to homogeneity by diethylaminoethyl (DEAE) cellulose ion exchange chromatography; with 84.89 % yield and 12.11 fold purity. LA showed stimulant activity against beta-mercaptoethanol and was greatly inhibited by Zn(2+) and Hg(2+) metal ions. Reduction of acrylamide in fried potatoes was detected by high performance liquid chromatography, which showed clear degradation of acrylamide by height and area (%) in the chromatograms of standard sample to that of the test sample. Hydrolysates analysis by high performance thin layer chromatography confirmed the test sample to be LA. PMID- 27186498 TI - The bizzare phenomenon of smokers' paradox in the immediate outcome post acute myocardial infarction: an insight into the Malaysian National Cardiovascular Database-Acute Coronary Syndrome (NCVD-ACS) registry year 2006-2013. AB - BACKGROUND: 'Smoker's paradox' is a controversial phenomenon of an unexpected favourable outcome of smokers post acute myocardial infarction. There are conflicting evidences from the literature so far. We investigate for the existence of this phenomenon in our post acute myocardial infarction patients. METHODS: We analysed 12,442 active smokers and 10,666 never-smokers diagnosed with STEMI and NSTEMI from the Malaysian National Cardiovascular Database-Acute Coronary Syndrome (NCVD-ACS) year 2006-2013 from 18 hospitals across Malaysia. Comparisons in the baseline characteristics, clinical presentation, in-hospital treatment and short term clinical outcome were made between the two groups. To compare the clinical outcome, an extensive multivariate adjustment was made to estimate the allcause mortality risk ratios for both groups. RESULTS: The active smokers were younger (smokers 53.7 years vs non-smokers 62.3 years P < 0.001) and had lower cardiovascular risk burden and other co-morbidities. STEMI is more common in smokers and intravenous thrombolysis was the main reperfusion therapy in both groups. Smokers had a higher rate of in-hsopital coronary revascularisation in NSTEMI group (21.6 % smokers vs 16.7 % non-smokers P < 0.001) but similar to non-smokers in the STEMI group. Multivariate adjusted mortality risk ratios showed significantly lower mortality risks of smokers at both in-hospital (RR 0.510 [95 % CI 0.442-0.613]) and 30-day post discharge (RR 0.534 [95 % CI 0.437-0.621]). CONCLUSION: Smoking seems to be associated with a favourable outcome post myocardial infarction. The phenomenon of 'smoker's paradox' is in fact a reality in our patients population. The definitive explanation for this unexpected protective effect of smoking remains unclear. PMID- 27186499 TI - Cervical myelopathy due to a solitary osteochondroma: a case report. AB - INTRODUCTION: Osteochondroma is the most common benign bone tumor. However, the incidence of osteochondroma in the spine is reported to be very rare. CASE DESCRIPTION: This report presents the case of a 57-year-old man who suffered from osteochondroma of the cervical spine. He had bilateral lower extremity pain for 3 years, developing pain of right upper extremity and gait disturbance. Plain radiographic images and computed tomography scans showed bony lesion in right C6/7 foramen and C6 lamina. Magnetic resonance images of whole spine showed severe compression of spinal cord at the C6/7 and spinal canal stenosis at the L3/4 level. First, we performed a surgery of the cervical spine, and removed the tumor covered with the cartilaginous cap. The pathological diagnosis of the tumor was osteochodroma. After the surgery, the symptoms on his right upper extremity improved smoothly. Because the bilateral lower extremity pain remained, a L3/4 partial laminectomy was performed 1 month later, and the symptom improved. At 1 year after his primary operation, we could not find a recurrence of the tumor. CONCLUSIONS: It is very important to perform a complete en bloc resection of the tumor (especially cartilaginous cap) to prevent the recurrence. PMID- 27186500 TI - Monitoring and behavior of unsaturated volcanic pyroclastic in the Metropolitan Area of San Salvador, El Salvador. AB - Field monitoring and laboratory results are presented for an unsaturated volcanic pyroclastic. The pyroclastic belongs to the latest plinian eruption of the Ilopango Caldera in the Metropolitan Area of San Salvador, and is constantly affected by intense erosion, collapse, slab failure, sand/silt/debris flowslide and debris avalanche during the rainy season or earthquakes. Being the flowslides more common but with smaller volume. During the research, preliminary results of rain threshold were obtained of flowslides, this was recorded with the TMS3 (a moisture sensor device using time domain transmission) installed in some slopes. TMS3 has been used before in biology, ecology and soil sciences, and for the first time was used for engineering geology in this research. This device uses electromagnetic waves to obtain moisture content of the soil and a calibration curve is necessary. With the behavior observed during this project is possible to conclude that not only climatic factors as rain quantity, temperature and evaporation are important into landslide susceptibility but also information of suction-moisture content, seepage, topography, weathering, ground deformation, vibrations, cracks, vegetation/roots and the presence of crust covering the surface are necessary to research in each site. Results of the field monitoring indicates that the presence of biological soil crusts a complex mosaic of soil, green algae, lichens, mosses, micro-fungi, cyanobacteria and other bacteria covering the slopes surface can protect somehow the steep slopes reducing the runoff process and mass wasting processes. The results obtained during the assessment will help explaining the mass wasting problems occurring in some pyroclastic soils and its possible use in mitigation works and early warning system. PMID- 27186501 TI - Biosorption of Congo Red from aqueous solution by crab shell residue: a comprehensive study. AB - The abundantly available bio waste, crab shell powder was used as an adsorbent for the removal of pollutants like Congo Red. The morphological, textural and chemical characterization of the biomass was done with SEM, XRD, EDS and FT-IR studies. The nature and mechanism of the process were determined from equilibrium, kinetic and thermodynamic studies. The results exhibited that the bio waste surface is fractured, rough and porous. It is composed of various surface functional groups which attracts organic pollutants. Equilibrium studies conclude Adsorption is a favorable process and it is a monolayer covering the surface. The maximum adsorption capacity, given by non-linear Langmuir isotherm was 124.9 mg/g. In kinetic studies pseudo-second order model best described the sorption kinetics compared to other models. Thermodynamic studies conclude that the process is spontaneous, endothermic and a physical adsorption. PMID- 27186502 TI - How eye movement and driving performance vary before, during, and after entering a long expressway tunnel: considering the differences of novice and experienced drivers under daytime and nighttime conditions. AB - INTRODUCTION: Driving environment in tunnels is quite different from the ordinary roadway sections, especially the entrance locations, which causes great difficulty in obtaining and interpreting information through fixations and saccades that are relevant to driving safety. Therefore, it is necessary to understand driver's visual behaviors while entering a tunnel so as to take the countermeasures for accident prevention. CASE DESCRIPTION: In order to identify the variation of driver's visual features during the process of tunnel entry, 18 participants were recruited to take part in a driving test conducted in real tunnel sections between Qipanguan toll and Jinshui toll of the G5 expressway in Shaanxi, China. During this test, the drivers' fixations, saccades and driving performances were captured for further analysis. DISCUSSION AND EVALUATION: The test data revealed that the driver's number of fixations, duration of fixations and number of saccades increased gradually at the transition zone. The number of fixations, duration of fixations and number of saccades then drop slightly until the end of the transition zone, and then rise just a little to a stable value after fully adapting to the driving conditions inside the tunnel. Meanwhile, the driver's number of saccades and saccade amplitude value decreased first, and then increased gradually until reaching a relatively stable value inside the tunnel. Additionally, drivers are more cautious at the transition zone, driving conservatively at lower speed, while decreasing their steering wheel angle and minimizing the vehicle's lateral deviation. Specially, novice drivers require a longer transition zone before tunnel entry compared to the experienced ones. Moreover, both novice and experienced drivers take more time to get prepared for tunnel entry while driving at night. CONCLUSION: Tunnel entrance section is far more dangerous, so drivers should be educated to get ready ahead for tunnel entry, drive cautiously at lower speed and pay full attention to the traffic flow conditions while driving through the tunnel, especially for the novice drivers in night tasks. Tunnel entrance is suggested to have easily identifiable frame design, with effective traffic signs placed at least 170 m before the entrance and gradually changeable LED lighting along the transition zone. All these suggestions provide insight into potential strategies for reducing and preventing traffic accidents and injuries at the tunnel locations. PMID- 27186503 TI - Improving the prediction of going concern of Taiwanese listed companies using a hybrid of LASSO with data mining techniques. AB - The purpose of this study is to establish rigorous and reliable going concern doubt (GCD) prediction models. This study first uses the least absolute shrinkage and selection operator (LASSO) to select variables and then applies data mining techniques to establish prediction models, such as neural network (NN), classification and regression tree (CART), and support vector machine (SVM). The samples of this study include 48 GCD listed companies and 124 NGCD (non-GCD) listed companies from 2002 to 2013 in the TEJ database. We conduct fivefold cross validation in order to identify the prediction accuracy. According to the empirical results, the prediction accuracy of the LASSO-NN model is 88.96 % (Type I error rate is 12.22 %; Type II error rate is 7.50 %), the prediction accuracy of the LASSO-CART model is 88.75 % (Type I error rate is 13.61 %; Type II error rate is 14.17 %), and the prediction accuracy of the LASSO-SVM model is 89.79 % (Type I error rate is 10.00 %; Type II error rate is 15.83 %). PMID- 27186504 TI - Analytical modeling of gas production rate in tight channel sand formation and optimization of artificial fracture. AB - Permeability variation in tight channel sand formation makes an important role in gas production. Based on the features of channel sand formation, a mathematical model has been established considering anisotropy of permeability. The analytical solutions were derived for productivity of both vertical wells and vertically fractured wells. Simulation results show that, gas production rate of anisotropic channel sand formation is less than that of isotropic formation. For vertically fractured well, artificial fracture direction, drainage radius, permeability ratio and fracture half-length have considerable influence on production rate. The optimum fracture direction should be deviated less than pi/8 from the maximum permeability direction (or the channel direction). In addition, the analytical model was verified by in situ measured data. The research provides theoretical basis for the development of tight channel sand gas reservoirs. PMID- 27186505 TI - Influence of salinity and temperature on uptake of perfluorinated carboxylic acids (PFCAs) by hydroponically grown wheat (Triticum aestivum L.). AB - Perfluoroalkyl substances (PFASs) have recently attracted increasing concerns due to their ubiquitous existence, adverse effects and persistence in environment. This study employed four perfluorinated carboxylic acids (PFCAs) to examine effects of salinity and temperature on the PFAS uptake in wheat, one of the major crops in the North China Plain. Wheat plants were grown in the spiked-PFCA hydroponic culture system at different salinities and temperatures. As expected, salinity and temperature significantly impacted the root uptake and translocation of wheat to four PFCAs, and the concentrations for each of PFCAs in wheat root and shoot increased with increasing salinity and temperature, respectively. PFCA concentrations at high salinity or high temperature were up to thrice those found at low salinity or low temperature. Except for perfluorobutanoic acid, the amount of PFCAs in root was always higher than that in shoot at the ranges of salinity and temperature tested. Additionally salinity and temperature were also capable of influencing the transfer factors (TFs) of four PFCAs, and significant increase was observed in the TFs in response to the increases in salinity and temperature. PMID- 27186506 TI - Effects of bloom-forming cyanobacterial extracellular polymeric substances on the adsorption of cadmium onto kaolinite: behaviors and possible mechanisms. AB - Cyanobacterial blooms result in high level of cyanobacterial extracellular polymeric substances (EPS) in water. The effects of bloom-forming cyanobacterial EPS on the distribution of Cd(II) in the interface between sediment and water is unknown. Clay is a main component in sediment. The effects of EPS, originated from a typical bloom-forming cyanobacterium Microcystis aeruginosa, on the adsorption and desorption characteristics of Cd(II) by kaolinite were investigated in this study. Results of XRD analysis indicated that cyanobacterial EPS bound on the surface of kaolinite. The composite of kaolinite + EPS showed higher adsorption capacity toward Cd(II) than pure kaolinite, and hydroxyl groups were involved in the adsorption processes. The data for the adsorption of Cd(II) by kaolinite are well fitted by both Langmuir model and Freundlich model, whereas only Freundlich model well describes the adsorption data of Cd(II) by the composite of kaolinite + EPS. The adsorption of Cd(II) onto kaolinite was an exothermic process, but it became an endothermic process after EPS incorporation. Results of desorption showed that EPS incorporation increased the adsorption of kaolinite toward Cd(II) through physical adsorption, ion exchange and complexation. PMID- 27186507 TI - Robot body self-modeling algorithm: a collision-free motion planning approach for humanoids. AB - Motion planning for humanoid robots is one of the critical issues due to the high redundancy and theoretical and technical considerations e.g. stability, motion feasibility and collision avoidance. The strategies which central nervous system employs to plan, signal and control the human movements are a source of inspiration to deal with the mentioned problems. Self-modeling is a concept inspired by body self-awareness in human. In this research it is integrated in an optimal motion planning framework in order to detect and avoid collision of the manipulated object with the humanoid body during performing a dynamic task. Twelve parametric functions are designed as self-models to determine the boundary of humanoid's body. Later, the boundaries which mathematically defined by the self-models are employed to calculate the safe region for box to avoid the collision with the robot. Four different objective functions are employed in motion simulation to validate the robustness of algorithm under different dynamics. The results also confirm the collision avoidance, reality and stability of the predicted motion. PMID- 27186508 TI - Results of screw fixation in Mason type II radial head fractures. AB - PURPOSE: The treatment of Mason type II fractures is controversial, and the aim of our study is to define the outcome of surgical treatment with screw fixation in the Mason type II radial head fracture. METHODS: The study was carried out between 2011 and 2015, and included 14 men and 9 women, with isolated Mason type II radial head fractures which were treated operatively with screw fixation. Cases involving the additional ligament injury or fractures in other areas, or having a follow-up period which is greater than 11 months were excluded. The clinical and radiological results of our patients were assessed, using the Mayo Elbow Performance Score (MEPS). RESULTS: The average MEPS was 95.86 points. 100 degree arcs of motion were attained by a total of 21 patients (91 %) for both flexion-extension and pronation-supination. Nevertheless, 2 patients (9 %) did not recover the 100 degree arcs for the flexion-extension. CONCLUSION: Anatomical reduction of type II radial head fractures through open surgery and fixation with screws can have favorable results. LEVEL OF EVIDENCE: Level IV, Retrospective design. PMID- 27186509 TI - Tuberculosis in infants: a retrospective study in China. AB - To describe the demographics, clinical characteristics and microbiologic findings of infant (<=2 years old) tuberculosis (TB) in a high TB burden country. Between Feb, 2007 and Jun, 2015, 115 TB infants who admitted to our hospital were enrolled in the study. Their clinicopathological characteristics were reviewed and analyzed. The mean age was 10.1 +/- 7.4 (SD) months, and 84 of 115 infants (73.0 %) were males. 23 patients (20.0 %) had isolated pulmonary TB, 18 patients (15.7 %) had pulmonary and extrapulmonary TB (EPTB), the remaining 74 patients (64.4 %) had exclusively EPTB. The most common site of EPTB was lymph node (n = 61), 54 cases were left axillary lymph node involvement. 49 of 51 patients (96.1 %) were validated by pathological examination, 5 of 57 patients (8.8 %) were positive on acid fast bacilli smear, and 27 of 103 patients (26.2 %) were confirmed by mycobacterial culture. 29 of 59 patients (49.2 %) were PPD positive, 14 of 30 patients (46.7 %) were T-SPOT.TB positive. The most common complaints of patients were lymph node swelling (53.0 %), fever (36.5 %), cough (28.7 %) and dyspnea (10.4 %). There was significant difference in the time before hospital admission among different types of tuberculosis (P < 0.01), fever was also a factor influencing the time (P < 0.05). In infants, the sensitivities of routine TB tests were low and emphasize the need for improved diagnostics; EPTB was more common than pulmonary TB, tuberculous lymphadenitis constituted a high proportion of EPTB; there appears to be an association between the incidence of axillary lymph node TB and BCG vaccination among infants in China. PMID- 27186510 TI - Treatment of limited-stage small cell lung cancer in the elderly, chemotherapy vs. sequential chemoradiotherapy vs. concurrent chemoradiotherapy: that's the question. AB - Chemotherapy is the mainstay of the treatment in limited disease (LD) and extended disease (ED) small cell lung cancer (SCLC) patients, while concurrent chemoradiotherapy (CRT) is the standard of care in healthy patients with LD. However, this intensive treatment is associated with significantly more toxicity in the subset of patients aged 70 years or more. To date, most of available data concerning CRT in elderly derived from retrospective analyzes, usually conducted on small samples of patients, poorly representative of this population. Modern CRT appears to confer a survival benefit compared to chemotherapy alone in a recent retrospective analysis conducted on elderly patients with LD-SCLC. Age alone should not be a contraindication for multimodality treatment in this subset of patients. PMID- 27186513 TI - Pros: concurrent chemo-radiotherapy remains the ideal treatment in fit patients with large volume unresectable stage III non-small cell lung cancer. AB - The debate of treating stage III, large volume non-small cell lung cancer (NSCLC) with definitive chemo-radiotherapy continues to be waged. A physically fit patient, having large volume and unresectable disease is the ideal candidate for this treatment approach. The ability of this patient population to successfully complete, and thereby benefit from an aggressive, combined treatment to improve local control and survival, drives the recommendation of treating oncologists for this approach. Until a phase III trial proves otherwise, concurrent chemo radiotherapy will remain the ideal treatment for fit patients having large volume unresectable stage III NSCLC. PMID- 27186514 TI - Cons: concurrent chemo-radiotherapy remains the ideal treatment in fit patients with inoperable large volume stage III non-small cell lung cancer. PMID- 27186512 TI - The role of epithelial to mesenchymal transition in resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer. AB - Inhibition of the epidermal growth factor receptor (EGFR) is an important strategy when treating non-small cell lung cancer (NSCLC) patients. However, intrinsic resistance or development of resistance during the course of treatment constitutes a major challenge. The knowledge on EGFR-directed tyrosine kinase inhibitors (TKIs) and their biological effect keeps increasing. Within the group of patients with EGFR mutations some benefit to a much higher degree than others, and for patients lacking EGFR mutations a subset experience an effect. Up to 70% of patients with EGFR mutations and 10-20% of patients without EGFR mutations initially respond to the EGFR-TKI erlotinib, but there is a severe absence of good prognostic markers. Despite initial effect, all patients acquire resistance to EGFR-TKIs. Multiple mechanisms have implications in resistance development, but much is still to be explored. Epithelial to mesenchymal transition (EMT) is a transcriptionally regulated phenotypic shift rendering cells more invasive and migratory. Within the EMT process lays a need for external or internal stimuli to give rise to changes in central signaling pathways. Expression of mesenchymal markers correlates to a bad prognosis and an inferior response to EGFR-TKIs in NSCLC due to the contribution to a resistant phenotype. A deeper understanding of the role of EMT in NSCLC and especially in EGFR-TKI resistance-development constitute one opportunity to improve the benefit of TKI treatment for the individual patient. Many scientific studies have linked the EMT process to EGFR TKI resistance in NSCLC and our aim is to review the role of EMT in both intrinsic and acquired resistance to EGFR-TKIs. PMID- 27186511 TI - Epigenetics in non-small cell lung cancer: from basics to therapeutics. AB - Lung cancer remains the number one cause of cancer-related deaths worldwide with 221,200 estimated new cases and 158,040 estimated deaths in 2015. Approximately 80% of cases are non-small cell lung cancer (NSCLC). The diagnosis is usually made at an advanced stage where the prognosis is poor and therapeutic options are limited. The evolution of lung cancer is a multistep process involving genetic, epigenetic, and environmental factor interactions that result in the dysregulation of key oncogenes and tumor suppressor genes, culminating in activation of cancer-related signaling pathways. The past decade has witnessed the discovery of multiple molecular aberrations that drive lung cancer growth, among which are epidermal growth factor receptor (EGFR) mutations and translocations involving the anaplastic lymphoma kinase (ALK) gene. This has translated into therapeutic agent developments that target these molecular alterations. The absence of targetable mutations in 50% of NSCLC cases and targeted therapy resistance development underscores the importance for developing alternative therapeutic strategies for treating lung cancer. Among these strategies, pharmacologic modulation of the epigenome has been used to treat lung cancer. Epigenetics approaches may circumvent the problem of tumor heterogeneity by affecting the expression of multiple tumor suppression genes (TSGs), halting tumor growth and survival. Moreover, it may be effective for tumors that are not driven by currently recognized druggable mutations. This review summarizes the molecular pathology of lung cancer epigenetic aberrations and discusses current efforts to target the epigenome with different pharmacological approaches. Our main focus will be on hypomethylating agents, histone deacetylase (HDAC) inhibitors, microRNA modulations, and the role of novel epigenetic biomarkers. Last, we will address the challenges that face this old-new strategy in treating lung cancer. PMID- 27186515 TI - Rebuttal from Prof. Kong and Dr. Rabatic. PMID- 27186516 TI - Rebuttal from Prof. Rodrigues. PMID- 27186518 TI - Erlotinib plus concurrent whole-brain radiation therapy for non-small cell lung cancers patients with multiple brain metastases. AB - Sequencing of the epidermal growth factor receptor (EGFR) gene to identify mutations in lung adenocarcinomas is routine in clinical practice. The use of tyrosine kinase inhibitors (TKIs) has transformed the management of patients with brain metastases harboring EGFR mutations, with improved response rates (RR) and survival. We evaluate the role of concurrent TKI therapy and radiotherapy in this group of patients, considering this data in the context of emerging concepts in this advancing field. PMID- 27186519 TI - Translational Lung Cancer Research is endorsed by the Brazilian Society of Thoracic Surgery. PMID- 27186517 TI - Prognostic value of the expression of estrogen receptor beta in patients with non small cell lung cancer: a meta-analysis. AB - BACKGROUND: Lung cancer remains the leading cause of cancer-related deaths in men and the second leading cause in women worldwide. It is becoming increasingly clear that estrogen and estrogen receptors are involved in the pathogenesis and development of lung cancer. However, observational studies on the prognostic role of estrogen receptor beta (ERbeta) in non-small cell lung cancer (NSCLC) are controversial. METHODS: To clarify the impact of ERbeta in NSCLC survival, we performed this meta-analysis that included eligible studies. The combined hazard ratios (HR) and their corresponding 95% confidence intervals (CIs) were calculated in terms of overall survival. RESULTS: A total of eleven studies with 3,300 patients were evaluable for this meta-analysis. Our results suggested that ERbeta overexpression had no relationship on survival of patients with NSCLC, the HR (95% CI) was 1.000 (0.954-1.047) overall. Moreover, there was no heterogeneity between the studies. CONCLUSIONS: ERbeta overexpression indicates no relationship of prognosis for patients with NSCLC. PMID- 27186520 TI - Retraction to platelets and their role in cancer evolution and immune system. AB - [This retracts the article on p. 713 in vol. 4, PMID: 26798580.]. PMID- 27186521 TI - Obstetrical, maternal characteristics and outcome of HIV-infected rapid progressor infants at Yaounde: a retrospective study. AB - BACKGROUND: Rapid progressors are exposed to HIV infection at an early stage of life, and the prognosis is poor without treatment. Reducing the proportion of infants who are rapid progressors, require strengthening strategies to achieve the highest level of performance for the PMTCT program. METHODS: This was a retrospective study carried out on HIV infected infants aged less than 12 months, clinically classified stage 4 (WHO) or having CD4 count <25%. We described maternal and obstetrical characteristics of HIV-infected rapid progressors using univariate and bivariate analysis. Patients' survival was monitored from the inclusion time to the end of the study. We then estimated their probability of survival with or without anti-retroviral (ARV) treatment from birth using the Kaplan-Meier method. RESULTS: The characteristics of the mothers of the 150 rapid progressors infants we included were: low level of education (OR=3.87; P=0.016), CD4 count less than 200/mm(3) (OR=43.3; P=0.000), absence of ARV prophylaxis (OR=6.02; P=0.043), or treatment with HAART (OR=5.74; P=0.000) during pregnancy. In the children, the most important findings were lack of co-trimoxazole prophylaxis (OR=11.61; P=0.000) and antiretroviral prophylaxis (OR=2.70; P=0.0344). The survival rate was 84.3% in infants who were receiving HAART as opposed to 43.3% in those who were not (P<0.05). CONCLUSIONS: HIV infected women who are eligible should start antiretroviral treatment prior to a pregnancy, in order to improve their immunological status. This measure associated to cotrimoxazole prophylaxis and ART could improve their survival. PMID- 27186522 TI - Surgical strategies for pediatric epilepsy. AB - Pediatric epilepsy is a debilitating condition that impacts millions of patients throughout the world. Approximately 20-30% of children with recurrent seizures have drug-resistant epilepsy (DRE). For these patients, surgery offers the possibility of not just seizure freedom but significantly improved neurocognitive and behavioral outcomes. The spectrum of surgical options is vast, ranging from outpatient procedures such as vagus nerve stimulation to radical interventions including hemispherectomy. The thread connecting all of these interventions is a common goal-seizure freedom, an outcome that can be achieved safely and durably in a large proportion of patients. In this review, we discuss many of the most commonly performed surgical interventions and describe the indications, complications, and outcomes specific to each. PMID- 27186525 TI - Chromosomal instability syndromes-the most classical and representative types of rare diseases. PMID- 27186523 TI - Emerging surgical therapies in the treatment of pediatric epilepsy. AB - In the approximately 1% of children affected by epilepsy, pharmacoresistance and early age of seizure onset are strongly correlated with poor cognitive outcomes, depression, anxiety, developmental delay, and impaired activities of daily living. These children often require multiple surgical procedures, including invasive diagnostic procedures with intracranial electrodes to identify the seizure-onset zone. The recent development of minimally invasive surgical techniques, including stereotactic electroencephalography (SEEG) and MRI-guided laser interstitial thermal therapy (MRgLITT), and new applications of neurostimulation, such as responsive neurostimulation (RNS), are quickly changing the landscape of the surgical management of pediatric epilepsy. In this review, the authors discuss these various technologies, their current applications, and limitations in the treatment of pediatric drug-resistant epilepsy, as well as areas for future research. The development of minimally invasive diagnostic and ablative surgical techniques together with new paradigms in neurostimulation hold vast potential to improve the efficacy and reduce the morbidity of the surgical management of children with drug-resistant epilepsy. PMID- 27186524 TI - Phenotypes and genotypes of the chromosomal instability syndromes. AB - As defined initially, chromosome instability syndromes (CIS) are a group of inherited conditions transmitted in autosomal recessive pattern characterised with both mental and physical development delay generally. They are also with other medical complications in individuals with CIS commonly including different degree of dysmorphics, organs/systems dys-function and high risk of cancer predisposition. Chromosomal breakage from CIS can be seen either in spontaneous breakage around 10-15% observed in Fanconi anemia or induced by clastogenic agents such as mitomycin (MMC), diepoxybutane (DEB). The spontaneous chromosome breakage is less common but it correlates with patient clinical severity. Relative high rates of some types of CIS can occur in certain ethnic groups. Individuals with CIS are commonly in childhood and these disorders are often lethal. Diagnosis is complicated usually because the symptoms presented from individuals with CIS may be varied and complex. Advances in molecular level have identified genes responsible for such group diseases/disorders demonstrated that CIS are characterized by the genome instability, defect in DNA repair mechanisms. Latest advances in high-throughput technologies have been increasing sequencing capabilities to facilitate more accurate data for such syndrome researches. CIS are the typical rare diseases and becoming more challenges in pediatrics clinic. In the last two decades, there were no many articles to review and analysis CIS together to comparing their phenotypes and genotypes. In this article, the similarity and differences of the phenotypes and genotypes of CIS were reviewed to understanding the whole profiles of CIS to assist laboratory genetic diagnostic services in CIS and for the confirmation from the clinical referrals. PMID- 27186526 TI - A case of Cushing ulcer in an 8-month-old patient with medulloblastoma. AB - The authors present the first case of a Cushing ulcer in an infant with medulloblastoma who, despite being administered stress ulcer prophylaxis, worsened after corticosteroids were initiated. An 8-month-old boy presented with progressive vomiting, lethargy, and decreased oral intake. Imaging revealed a heterogeneous fourth ventricular mass. Preoperatively, the patient was started on dexamethasone. The patient underwent an uncomplicated external ventricular drain placement and suboccipital craniotomy for resection of the lesion. The results of the pathological analysis were consistent with medulloblastoma. Postoperatively, the patient had melanotic stools, which were reported to be occurring for months prior to presentation. Two proximal duodenal bulb ulcers were found and required definitive surgical repair. The patient recovered from the acute postsurgical course after continued stress ulcer prophylaxis and is currently undergoing chemotherapy. PMID- 27186527 TI - An extremely rare case of metastatic retinoblastoma of parotids presenting as a massive swelling in a child. AB - Retinoblastoma (Rb) is a common childhood malignancy but bilateral Rb with metastasis to parotids is very uncommon. To the best of our knowledge, bilateral Rb metastasizing to parotids is very rare and this is the fifth such case reported in world literature till date in a 2-year-old male child who underwent exenteration of left eye for bilateral Rb and later developed recurrent metastasis to left parotid requiring parotidectomy. A year later he presented again with swelling left parotid region extending from occipital region reaching upto left anterior chest wall with intra-cranial extension on magnetic resonance imaging. Histopathological examination of the parotid swelling and immunohistochemistry showed metastasis from Rb. He was treated with chemotherapy followed by radiotherapy to local site and brain to which he responded well. Presently on regular follow up without any signs of locoregional and distal metastasis. Till date different types of primary parotid tumors have been reported in literature but a metastatic parotid tumor is extremely rare and therefore this case is being reported to highlight the extreme rarity, the diagnostic and therapeutic challenges, the highly aggressive nature and overall dismal prognosis of this disease entity. PMID- 27186528 TI - Periungual myiasis caused by wohlfahrtia magnifica mimicking an ingrown toenail. AB - Myiasis is the infestation of organs and tissues of human being or other vertebrate animals with dipterous larvae. Myiasis is generally rare in humans, especially in children. We present the first case of periungual myiasis by Wohlfahrtia magnifica in a 5-year-old female. Wohlfahrtia magnifica is an obligatory parasite, which has been described as cause of ophthalmomyiasis, otomyiasis, oral myiasis, vulvar myiasis and wound myiasis. Treatment of myiasis and ingrown toenail is generally non-operative although both entities can be serious and/or non-responsive to conservative therapy. PMID- 27186529 TI - The skinny on metabolic syndrome in adolescents. PMID- 27186530 TI - Delayed cord clamping in red blood cell alloimmunization: safe, effective, and free? AB - Hemolytic disease of the newborn (HDN), an alloimmune disorder due to maternal and fetal blood type incompatibility, is associated with fetal and neonatal complications related to red blood cell (RBC) hemolysis. After delivery, without placental clearance, neonatal hyperbilirubinemia may develop from ongoing maternal antibody-mediated RBC hemolysis. In cases refractory to intensive phototherapy treatment, exchange transfusions (ET) may be performed to prevent central nervous system damage by reducing circulating bilirubin levels and to replace antibody-coated red blood cells with antigen-negative RBCs. The risks and costs of treating HDN are significant, but appear to be decreased by delayed umbilical cord clamping at birth, a strategy that promotes placental transfusion to the newborn. Compared to immediate cord clamping (ICC), safe and beneficial short-term outcomes have been demonstrated in preterm and term neonates receiving delayed cord clamping (DCC), a practice that may potentially be effective in cases RBC alloimmunization. PMID- 27186531 TI - Sperm retrieval in adolescent males with Klinefelter syndrome: medical and ethical issues. PMID- 27186532 TI - Translational Pediatrics is indexed in PubMed/PubMed Central (PMC). PMID- 27186533 TI - Interdisciplinary Researches in Iran IV: The Road Map of Ocular Image Analysis Research Group. PMID- 27186535 TI - A Novel Thresholding Based Algorithm for Detection of Vertical Root Fracture in Nonendodontically Treated Premolar Teeth. AB - In this paper, an efficient algorithm is proposed for detection of vertical root fractures (VRFs) in periapical (PA), and cone-beam computed tomography (CBCT) radiographs of nonendodontically treated premolar teeth. PA and CBCT images are divided into some sub-categories based on the fracture space between the two fragments as small, medium, and large for PAs and large for CBCTs. These graphics are first denoised using the combination of block matching 3-D filtering, and principle component analysis model. Then, we proposed an adaptive thresholding algorithm based on the modified Wellner model to segment the fracture and canal. Finally, VRFs are identified with a high accuracy through applying continuous wavelet transform on the segmented radiographs and choosing the most optimal value for sub-images based on the lowest interclass variance. Performance of the proposed algorithm is evaluated utilizing the different tested criteria. Results illustrate that the range of specificity deviations for PA and CBCT radiographs are 99.69 +/- 0.22 and 99.02 +/- 0.77, respectively. Furthermore, the sensitivity changes from 61.90 to 77.39 in the case of PA and from 79.54 to 100 in the case of CBCT. Based on our statistical evaluation, the CBCT imaging has the better performance in comparison with PA ones, so this technique could be a useful tool for clinical applications in determining the VRFs. PMID- 27186536 TI - Radio Frequency Ultrasound Time Series Signal Analysis to Evaluate High-intensity Focused Ultrasound Lesion Formation Status in Tissue. AB - High-intensity focused ultrasound (HIFU) is a novel treatment modality used by scientists and clinicians in the recent decades. This modality has had a great and significant success as a noninvasive surgery technique applicable in tissue ablation therapy and cancer treatment. In this study, radio frequency (RF) ultrasound signals were acquired and registered in three stages of before, during, and after HIFU exposures. Different features of RF time series signals including the sum of amplitude spectrum in the four quarters of the frequency range, the slope, and intercept of the best-fit line to the entire power spectrum and the Shannon entropy were utilized to distinguish between the HIFU-induced thermal lesion and the normal tissue. We also examined the RF data, frame by frame to identify exposure effects on the formation and characteristics of a HIFU thermal lesion at different time steps throughout the treatment. The results obtained showed that the spectrum frequency quarters and the slope and intercept of the best fit line to the entire power spectrum both increased two times during the HIFU exposures. The Shannon entropy, however, decreased after the exposures. In conclusion, different characteristics of RF time series signal possess promising features that can be used to characterize ablated and nonablated tissues and to distinguish them from each other in a quasi-quantitative fashion. PMID- 27186534 TI - Quantitative Assessment of Retinopathy Using Multi-parameter Image Analysis. AB - A multi-parameter quantification method was implemented to quantify retinal vascular injuries in microscopic images of clinically relevant eye diseases. This method was applied to wholemount retinal trypsin digest images of diabetic Akita/+, and bcl-2 knocked out mice models. Five unique features of retinal vasculature were extracted to monitor early structural changes and retinopathy, as well as quantifying the disease progression. Our approach was validated through simulations of retinal images. Results showed fewer number of cells (P = 5.1205e-05), greater population ratios of endothelial cells to pericytes (PCs) (P = 5.1772e-04; an indicator of PC loss), higher fractal dimension (P = 8.2202e 05), smaller vessel coverage (P = 1.4214e-05), and greater number of acellular capillaries (P = 7.0414e-04) for diabetic retina as compared to normal retina. Quantification using the present method would be helpful in evaluating physiological and pathological retinopathy in a high-throughput and reproducible manner. PMID- 27186537 TI - Assessment of the Focal Hepatic Lesions Using Diffusion Tensor Magnetic Resonance Imaging. AB - The goal is assessing the diffusion magnetic resonance imaging (dMRI) method efficiency in characterizing focal hepatic lesions (FHLs). About 28-FHL patients were studied in Radiology and Clinical Imaging Department of our University Hospital using 1.5 Tesla MRI system between January 2010 and June 2011. Patients underwent hepatic MRI consisting of dynamic T1- and T2-weighted imaging. The dMRI was performed with b-values of 200 s/mm(2) and 600 s/mm(2). About 42 lesions measuring more than 1 cm were studied including the variation of the signal according to the b-value and the apparent diffusion coefficient (ADC). The diagnostic imaging reference was based on standard MRI techniques data for typical lesions and on histology after surgical biopsy for atypical lesions. About 38 lesions were assessed including 13 benign lesions consisting of 1 focal nodular hyperplasia, 8 angiomas, and 4 cysts. About 25 malignant lesions included 11 hepatocellular carcinoma, 9 hepatic metastases, 1 cholangiocarcinoma, and 4 lymphomas. dMRI of soft lesions demonstrated higher ADC of 2.26 +/- 0.75 mm(2)/s, whereas solid lesions showed lower ADC 1.19 +/- 0.33 mm(2)/s with significant difference (P = 0.05). Discrete values collections were noticed. These results were correlated to standard MRI and histological findings. Sensitivity of 93% and specificity of 84% were found in diagnoses of malignant tumors with an ADC threshold of 1.6 * 10(-3) mm(2)/s. dMRI is important characterization method of FHL. However, it should not be used as single criteria of hepatic lesions malignity. MRI, clinical, and biological data must be correlated. Significant difference was found between benign and solid malignant lesions without threshold ADC values. Hence, it is difficult to confirm ADC threshold differentiating the lesion classification. PMID- 27186538 TI - Synthesis and In vitro Evaluation of Electrodeposited Barium Titanate Coating on Ti6Al4V. AB - Osseointegration has been the concern of implantology for many years. Researchers have used various ceramic coatings for this purpose; however, piezoelectric ceramics (e.g., barium titanate [BTO]) are a novel field of interest. In this regard, BTO (BaTiO3) coating was fabricated by electrophoretic deposition on Ti6Al4V medical alloy, using sol-gel-synthesized nanometer BTO powder. Structure and morphologies were studied using X-ray diffraction and scanning electron microscopy (SEM), respectively. Bioactivity response of coated samples was evaluated by SEM and inductively coupled plasma (ICP) analysis after immersion in simulated body fluid (SBF). Cell compatibility was also studied via MTT assay and SEM imaging. Results showed homogenous coating with cubic structure and crystallite size of about 41 nm. SEM images indicated apatite formation on the coating after 7 days of SBF immersion, and ICP analysis approved ions concentration decrement in SBF. Cells showed flattened morphology in intimate contact with coating after 7 days of culture. Altogether, coated samples demonstrated appropriate bioactivity and biocompatibility. PMID- 27186539 TI - Multiple MTS Assay as the Alternative Method to Determine Survival Fraction of the Irradiated HT-29 Colon Cancer Cells. AB - A multiple colorimetric assay has been introduced to evaluate the proliferation and determination of survival fraction (SF) of irradiated cells. The estimation of SF based on the cell-growth curve information is the major advantage of this assay. In this study, the utility of multiple-MTS assay for the SF estimation of irradiated HT-29 colon cancer cells, which were plated before irradiation, was evaluated. The SF of HT-29 colon cancer cells under irradiation with 9 MV photon was estimated using multiple-MTS assay and colony assay. Finally, the correlation between two assays was evaluated. Results showed that there are no significant differences between the SF obtained by two assays at different radiation doses (P > 0.05), and the survival curves have quite similar trends. In conclusion, multiple MTS-assay can be a reliable method to determine the SF of irradiated colon cancer cells that plated before irradiation. PMID- 27186540 TI - Prediction of the Wrist Joint Position During a Postural Tremor Using Neural Oscillators and an Adaptive Controller. AB - The prediction of the joint angle position, especially during tremor bursts, can be useful for detecting, tracking, and forecasting tremors. Thus, this research proposes a new model for predicting the wrist joint position during rhythmic bursts and inter-burst intervals. Since a tremor is an approximately rhythmic and roughly sinusoidal movement, neural oscillators have been selected to underlie the proposed model. Two neural oscillators were adopted. Electromyogram (EMG) signals were recorded from the extensor carpi radialis and flexor carpi radialis muscles concurrent with the joint angle signals of a stroke subject in an arm constant-posture. The output frequency of each oscillator was equal to the frequency corresponding to the maximum value of power spectrum related to the rhythmic wrist joint angle signals which had been recorded during a postural tremor. The phase shift between the outputs of the two oscillators was equal to the phase shift between the muscle activation of the wrist flexor and extensor muscles. The difference between the two oscillators' output signals was considered the main pattern. Along with a proportional compensator, an adaptive neural controller has adjusted the amplitude of the main pattern in such a way so as to minimize the wrist joint prediction error during a stroke patient's tremor burst and a healthy subject's generated artificial tremor. In regard to the range of wrist joint movement during the observed rhythmic motions, a calculated prediction error is deemed acceptable. PMID- 27186541 TI - The law of therapeutic parsimony. PMID- 27186542 TI - The Draupadi of dyslipidemia: Familial hypercholesterolemia. PMID- 27186544 TI - Clinical, hormonal and radiological profile of 46XY disorders of sexual development. AB - BACKGROUND AND OBJECTIVES: 46 XY disorders of sexual development (DSD) cover a wide spectrum of phenotypes ranging from unambiguous female genitalia to ambiguous male genitalia with hypospadias or dysgenetic gonads. Management of these patients depends on the cause of DSD, degree of feminization, age at presentation, and gender orientation. The aim of this study was to evaluate the presentation and management of patients with 46XY DSD at our center. PATIENTS AND METHODS: All new and old patients of 46XY DSD attending the endocrine OPD in a period of 16 months were included in this study. Clinical, cytogenetic, hormonal, and radiological evaluation were done to identify the cause of DSD. RESULTS: Among 19 patients, eight were diagnosed with disorders of gonadal development (one with complete gonadal dysgenesis, four with partial gonadal dysgenesis, two with congenital bilateral anorchia, and one with ovotesticular DSD) and eight with disorders of androgen synthesis and action (one with complete androgen insensitivity syndrome [AIS], three with partial AIS and four with 5alpha reductase deficiency). In three patients, a definitive diagnosis could not be made. CONCLUSIONS: Management of patients with DSD depends on etiology, gender assignment, gender orientation, hormonal treatment, genital surgery, and consequent psychosocial implications. Due to the overlapping clinical and biochemical parameters in different subsets of DSD, only a preliminary etiological diagnosis can be made in some cases. Genetic studies with long-term follow-up are required for an accurate diagnosis. PMID- 27186543 TI - Efficacy and safety of biphasic insulin aspart and biphasic insulin lispro mix in patients with type 2 diabetes: A review of the literature. AB - Type 2 diabetes (T2D) represents an escalating burden worldwide, particularly in China and India. Compared with Caucasians, Asian people with diabetes have lower body mass index, increased visceral adiposity, and postprandial glucose (PPG)/insulin resistance. Since postprandial hyperglycemia contributes significantly to total glycemic burden and is associated with heightened cardiovascular risk, targeting PPG early in T2D is paramount. Premixed insulin regimens are widely used in Asia due to their convenience and effectiveness. Data from randomized controlled trials and observational studies comparing efficacy and safety of biphasic insulin aspart 30 (BIAsp 30) with biphasic insulin lispro mix (LM 25/50) and versus other insulin therapies or oral antidiabetic drugs (OADs) in T2D demonstrated that BIAsp 30 and LM 25/50 were associated with similar or greater improvements in glycemic control versus comparator regimens, such as basal-bolus insulin, in insulin-naIve, and prior insulin users. Studies directly comparing BIAsp 30 and LM 25 provided conflicting glycemic control results. Safety data generally showed increased hypoglycemia and weight gain with premixed insulins versus basal-bolus insulin or OADs. However, large observational trials documented improvements in glycated hemoglobin, PPG, and hypoglycemia with BIAsp 30 in multi-ethnic patient populations. In summary, this literature review demonstrates that premixed insulin regimens are an appropriate and effective treatment choice in T2D. PMID- 27186545 TI - Outcome and preferences in female-to-male subjects with gender dysphoria: Experience from Eastern India. AB - CONTEXT: Awareness of gender dysphoria (GD) and its treatment is increasing. There is paucity of scientific data from India regarding the therapeutic options being used for alleviating GD, which includes psychotherapy, hormone, and surgical treatments. AIM: To study the therapeutic options including psychotherapy, hormone, and surgical treatments used for alleviating GD. SETTINGS AND DESIGN: This is a retrospective study of treatment preferences and outcome in 18 female-to-male (FTM) transgender subjects who presented to the endocrine clinic. RESULTS: The mean follow-up was 1.6 years and only one subject was lost to follow-up after a single visit. All subjects desiring treatment had regular counseling and medical monitoring. All FTM subjects were cross-dressing. Seventeen (94.4%) FTM subjects were receiving cross-sex hormone therapy, in the form of testosterone only (61.1%) or gonadotropin-releasing hormone (GnRH) agonist in combination with testosterone (11.1%) or medroxyprogesterone acetate (MPA) depot in combination with testosterone (22.2%). FTM subjects preferred testosterone or testosterone plus MPA; very few could afford GnRH therapy. Testosterone esters injection was preferred by most (72.2%) subjects as it was most affordable while 22.2% chose 3 monthly injections of testosterone undecanoate for convenience and better symptomatic improvement, but it was more expensive. None preferred testosterone gels because of cost and availability concerns. About 33.3% of our subjects underwent mastectomy, 38.9% had hysterectomy with bilateral salpingo-oophorectomy, and only one subject underwent phalloplasty. About 16.7% of FTM subjects presented with prior mastectomy depicting a high prevalence of unsupervised or poorly supervised surgeries not following protocol wise approach. CONCLUSION: Notwithstanding of advances in Standards of Care in the Western world, there is lack of awareness and acceptance in the FTM subjects, about proper and timely protocol-wise management options leading to suboptimal physical, social, and sexual results. PMID- 27186546 TI - Th1/Th2 cytokines in Type 1 diabetes: Relation to duration of disease and gender. AB - BACKGROUND: T-cells are important in the pathogenesis of Type 1 diabetes (T1D). However, the exact role of T-cell subpopulations in this pathway remains unknown. The purpose of this study was to assess the expression pattern of T helper 1 (Th1) interferon-gamma (IFN-gamma) and Th2 interleukin-4 (IL-4) cytokines and their relationship with sex and disease duration in T1D patients. MATERIALS AND METHODS: This study was conducted on 21 T1D patients and 22 healthy subjects. Gene expression analysis of peripheral blood mononuclear cells (PBMCs) was performed using real-time reverse transcriptase polymerase chain reaction. RESULTS: IFN-gamma gene expression was significantly lower in T1D patients compared with controls (P < 0.05). Conversely, IL-4 mRNAs were significantly increased in the PBMCs from patients as compared to controls (P < 0.05). There was no significant difference in the expression of IL-4 and IFN-gamma between men and women with T1D (P > 0.05) while IL-4 mRNA expression in male patients was about 1.9 folds higher than female patients. Moreover, IFN-gamma mRNA expression in female patients was about 1.8 folds lower than male patients. Patients were divided into two groups regarding their disease duration: <10 years and >10 years. A significant increase in the IL-4 expression was observed between two groups of patients compared to controls (P < 0.0001). Conversely, there was a significant difference in the expression of IFN-gamma only between patients with more than 10 years of disease duration (P = 0.02). CONCLUSION: These data propose supplementary implications for the role of Th1/Th2 imbalance in T1D immunopathogenesis. Moreover, factors such as sex and disease duration may have some influence on cytokine mRNA expression. PMID- 27186547 TI - Effect of maternal and neonatal factors on cord blood thyroid stimulating hormone. AB - BACKGROUND: Congenital hypothyroidism (CH) is most common preventable cause of mental retardation in children. Cord blood Thyroid Stimulating Hormone (CBTSH) level is an accepted screening tool for CH. OBJECTIVES: To study CBTSH profile in neonates born at tertiary care referral center and to analyze the influence of maternal and neonatal factors on their levels. DESIGN: Cross retrospective sectional study. METHODS: Study population included 979 neonates (males = 506 to females = 473). The CBTSH levels were estimated using electrochemiluminescence immunoassay on Cobas analyzer. Kit based cut-offs of TSH level were used for analysis. All neonates with abnormal CBSTH levels, were started on levothyroxine supplementation 10 MUg/Kg/day and TSH levels were reassessed as per departmental protocol. RESULTS: The mean CBTSH was 7.82 MUIU/mL (Range 0.112 to 81.4, SD = 5.48). The mean CBTSH level was significantly higher in first order neonates, neonates delivered by assisted vaginal delivery and normal delivery, delivered at term or preterm, neonates with APGAR score <5 and those needing advanced resuscitation after birth. The CBTSH level >16.10 and <1.0 MUIU/mL was found in 4.39 % and 1.02 % neonates respectively. The prevalence rate of CBTSH level >16.1 MUIU/mL was significantly higher in neonates delivered by assisted vaginal delivery and normal delivery, term and preterm neonates, APAGR score of <5, presence of fetal distress, need for resuscitation beyond initial steps and in those with birth weight of <1.5 Kg. Three neonates were confirmed to have CH after retesting of TSH level. CONCLUSIONS: The CBTSH estimation is an easy, non invasive method for screening for CH. The cutoff level of CB TSH (MUIU/mL) >16.10 and <1.0 led to a recall of 5.41% of neonates which is practicable given the scenario in our Country. The mode of delivery and perinatal stress factors have a significant impact on CBTSH levels and any rise to be seen in the light of these factors. The prevalence rate of CH after recall was ~3 in 1000 live births. PMID- 27186548 TI - Leptin and body mass index in polycystic ovary syndrome. AB - OBJECTIVE: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with obesity. Human and animal studies showed a direct relationship between leptin level and obesity, however, results from different studies were mixed. This study investigated the status of leptin level in PCOS and its relationship with body mass index (BMI) in a group of Iranian women with PCOS. METHODS: In this cross-sectional study, 40 women with PCOS and 36 healthy women were assigned to experimental and control groups, respectively. Those in the PCOS group were not prescribed any medications for 3 months prior to the study. Fasting blood samples were then collected during the 2(nd) or 3(rd) day of menstruation for laboratory measurement of serum total leptin, blood glucose (fasting blood sugar), serum insulin, follicle-stimulating hormone, and luteinizing hormone (LH). RESULTS: Mean BMI of the PCOS and control groups were 26.62 +/- 4.03 kg/m(2) and 23.52 +/- 2.52 kg/m(2), respectively (P = 0.006). The mean total leptin in the PCO group was also 10.69 +/- 5.37 ng/mL and 5.73 +/- 2.36 ng/mL in the control group (P = 0.0001). A significant relationship was found between leptin level and BMI as well as LH level among women with PCOS (P < 0.05). However, there was no significant correlation between leptin and insulin (P > 0.05). CONCLUSION: The results of this study indicated an increased leptin level among women with PCOS that positively associated with BMI and LH. PMID- 27186550 TI - Efficacy and safety of Vitamin D supplementation during pregnancy: A randomized trial of two different levels of dosing on maternal and neonatal Vitamin D outcome. AB - INTRODUCTION: Pregnant women represent a typical group susceptible to dietary and mineral deficiencies. This study was sought to assess the efficacy and safety of various doses of 25-hydroxyvitamin D (25[OH]D) supplementation during pregnancy and ratify the inadequacy of the recommended daily allowance for Vitamin D in vulnerable groups. MATERIALS AND METHODS: A total of 100 pregnant women were included in this open-label, parallel group, prospective, randomized, and controlled trial. Study subjects were assigned to four treatment groups: Group 1 (n = 26), 1000 IU of Vitamin D daily; Group 2 (n = 21), 30,000 IU of Vitamin D monthly; Group 3 (n = 27), 2000 IU of Vitamin D daily; and Group 4 (n = 26), 60,000 IU Vitamin D monthly. Group 1 and 2 were further analyzed together as Group 1K (1000 IU daily and 30,000 IU monthly), and Group 3 and 4 as Group 2K (2000 IU daily and 60,000 IU monthly). The analysis was done on an intention to treat basis. RESULTS: A total of 87 patients completed the study; 21 in Group 1, 25 in Group 2, 18 in Group 3, and 23 in Group 4. The levels of 25(OH)D at baseline ranged from 1.3 to 58.0 with a mean of 24.2 +/- 15.1 ng/ml. Postsupplementation, 25(OH)D levels ranged from 11.5 to 70.3 with a mean of 40.2 +/- 12.2 ng/ml. The postsupplementation levels of 25(OH)D were higher in Group 2K (42.86 +/- 12.83) than in Group 1K (36.96 +/- 10.56) with P value of 0.023. CONCLUSION: We concluded that Vitamin D supplementation with 2000 IU/day or 60,000 IU/month is very effective and safe in achieving Vitamin D sufficiency in pregnant women. PMID- 27186549 TI - Adherence to diabetes care processes at general practices in the National Capital Region-Delhi, India. AB - AIM: To assess the level of adherence to diabetes care processes, and associated clinic and patient factors at general practices in Delhi, India. METHODS: We interviewed physicians (n = 23) and patients with diabetes (n = 406), and reviewed patient charts at general practices (government = 5; private = 18). We examined diabetes care processes, specifically measurement of weight, blood pressure (BP), glycated hemoglobin (HbA1c), lipids, electrocardiogram, dilated eye, and a foot examination in the last one year. We analyzed clinic and patient factors associated with a number of care processes achieved using multilevel Poisson regression model. RESULTS: The average number of clinic visits per patient was 8.8/year (standard deviation = 5.7), and physicians had access to patient's previous records in only 19.7% of patients. Dilated eye exam, foot exam, and electrocardiogram were completed in 7.4%, 15.1%, and 29.1% of patients, respectively. An estimated 51.7%, 88.4%, and 28.1% had >=1 measurement of HbA1c, BP, and lipids, respectively. Private clinics, physician access to patient's previous records, use of nonphysicians, patient education, and the presence of diabetes complication were positively associated with a number of care processes in the multivariable model. CONCLUSION: Adherence to diabetes care processes was suboptimal. Encouraging implementation of quality improvement strategies like Chronic Care Model elements at general practices may improve diabetes care. PMID- 27186551 TI - Awareness among tertiary care doctors about Pharmacovigilance Programme of India: Do endocrinologists differ from others? AB - BACKGROUND AND OBJECTIVES: Reporting adverse drug reactions (ADRs) associated with drug use is an important factor in patient safety. Majority of ADRs are preventable through improved prescribing and monitoring. Endocrinologists prescribe drugs with actions on almost all organs and for relatively longer durations. ADR are expected following the use of these drugs. Pharmacovigilance is the study of drug-related adverse effects aimed at protecting patients and public from drug-related harms. The concept of pharmacovigilance is relatively new in India, and this survey is an attempt to explore awareness among doctors of an establishing institution of national importance. MATERIALS AND METHODS: The survey was conducted on faculty and resident doctors by administering a written structured questionnaire in a voluntary manner. The questionnaire contained questions meant to evaluate their awareness, understanding, and misconception about ADR reporting. Identity of the responder was kept confidential. RESULTS: A total of 106 (faculty = 56; residents = 50) participated in survey. The most common cause cited for not reporting an ADR was "do not know how to report" by 64.15%. Majority of them (64%) had no information about the Pharmacovigilance Programme of India (PvPI), and only few (8.5%) had actually reported or published an ADR. INTERPRETATION AND CONCLUSIONS: ADRs are major public health problem that needs to be addressed at all levels of health care. High index of clinical suspicion are crucial for their timely detection and management. Various educational interventions have shown to improve medical professionals' awareness, understanding about ADRs and in their reporting behavior. PvPI is an important initiative toward ensuring patient safety. PMID- 27186553 TI - Study of differences in presentation, risk factors and management in diabetic and nondiabetic patients with acute coronary syndrome. AB - OBJECTIVES: To compare clinical characteristics, treatment, and utilization of evidence-based medicines at discharge from hospital in acute coronary syndrome (ACS) patients with or without diabetes at a tertiary care cardiac center in India. METHODS: We performed an observational study in consecutive patients discharged following management of ACS. We obtained demographic details, comorbid conditions, and cardiovascular risk factors, physical and biochemical parameters, and management. Descriptive statistics are reported. RESULTS: We enrolled 100 patients (diabetics = 28) with mean age of 59.0 +/- 10.8 years (diabetics 59.3 +/ 11.6, nondiabetics 58.9 +/- 8.5). Forty-nine patients had ST-elevation myocardial infarction (STEMI) (diabetics = 14, 28.7%) while 51 had nonSTEMI/unstable angina (diabetics = 14, 27.4%) (P = nonsignificant). Among diabetics versus nondiabetics there was greater prevalence (%) of hypertension (78.6% vs. 44.4%), obesity (25.0% vs. 8.3%), abdominal obesity (85.7% vs. 69.4%) and sedentary activity (89.2% vs. 77.8%), and lower prevalence of smoking/tobacco use (10.7% vs. 25.0%) (P < 0.05). In STEMI patients 28 (57.1%) were thrombolysed (diabetes 17.8% vs. 31.9%), percutaneous coronary interventions (PCI) was in 67.8% diabetics versus 84.7% nondiabetics and coronary bypass surgery in 21.4% versus 8.3%. At discharge, in diabetics versus nondiabetics, there was similar use of angiotensin converting enzyme inhibitors (67.9% vs. 69.4%) and statins (100.0% vs. 98.6%) while use of dual antiplatelet therapy (85.7% vs. 95.8%) and beta-blockers (64.3% vs. 73.6%) was lower (P < 0.05). CONCLUSIONS: Diabetic patients with ACS have greater prevalence of cardiometabolic risk factors (obesity, abdominal obesity, and hypertension) as compared to nondiabetic patients. Less diabetic patients undergo PCIs and receive lesser dual anti platelet therapy and beta-blockers. PMID- 27186552 TI - Evaluation of oxidative stress and thyroid hormone status in hemodialysis patients in Gorgan. AB - AIMS: The aim of this study focused on serum malondialdehyde (MDA) levels and erythrocyte superoxide dismutase (SOD) and catalase (CAT) activities in hemodialysis patients and compared with control groups. MATERIALS AND METHODS: Forty-five hemodialyzed patients and 45 control groups recruited in this study. Serum creatinine and urea, thyroid hormones (THs) levels and erythrocyte antioxidant enzyme activities were determined. RESULTS: Hemodialysis (HD) patients showed higher levels of MDA than control groups (P < 0.01), but the levels of thyroxin (T3), free triiodothyronine (fT3), and free thyroxin (fT4), SOD and CAT were low in HD patients (P < 0.01). Serum T3, fT3, and fT4 levels were significantly negative correlated with MDA (P < 0.01). CONCLUSION: It is concluded that serum lipid peroxidation is markedly increased in HD patients. This means that elevated reactive oxygen species may interact with the lipid molecules in HD patients. HD may cause significant changes in TH levels. Thyroid stimulating hormone level in HD patients is slightly similar to that of control groups. This suggests that thyroid is able to resynthesize for hormonal urinary losses. PMID- 27186554 TI - Estimation of thyroglobulin in lymph node aspirates: Pilot experience from a tertiary referral cancer center. AB - BACKGROUND: Assessment of cervical lymph node involvement in patients with thyroid cancer either during preoperative surgical mapping or detection of recurrences during follow-up is a crucial step in the management of differentiated thyroid cancers (DTCs). In most patients, fine needle aspiration cytology (FNAC) confirms the presence of metastasis in lymph node. However, in cases of paucicellular lymph node aspirate or discordant sonogram and cytology results, thyroglobulin (Tg) measurement in the lymph node aspirate (FNA-Tg) is useful and a value >1 ng/ml is considered consistent with metastatic disease. CONTEXT: The addition of FNAC to the US improves the specificity, but 5-10% are nondiagnostic and 6-8% rate of false-negative results. Several studies have reported that the detection of Tg in FNA-needle washes improves the evaluation of suspicious lymph nodes in patients with DTC.Data from Indian centers on FNA-Tg are limited. AIMS: We piloted the utility of FNA-Tg in patients with sonographically suspicious cervical lymph node enlargement in the setting of suspicious thyroid nodule or in the follow-up of thyroid cancer. SETTINGS AND DESIGN: Prospective data collection. RESULTS: We measured Tg in 13 lymph node aspirates (12 patients, 10 females) among whom 4 patients had a total thyroidectomy and 1 had a hemithyroidectomy. Eight of the 13 lymph node aspirates had FNA-Tg values >150 ng/ml, all of them had unequivocal malignant cytology and four among them had proven metastatic DTC on surgical pathology. The median FNA Tg of the patients with malignant cytology was 7550 ng/ml with a range of 162 30,000 ng/ml. Among the remaining 5 lymph node aspirate, 2 lymph nodes showed cytological features suggestive of reactive lymphadenitis (FNA-Tg <0.2 ng/ml) and were not operated, 1 had a high-grade malignancy consistent with anaplastic thyroid cancer (FNA-Tg <0.2 ng/ml), and 2 had nondiagnostic cytology (one had non caseating granuloma on surgical pathology [FNA-Tg 1.3 ng/ml] and in the other patient [FNA-Tg <0.2 ng/ml] surgical intervention was deferred). CONCLUSIONS: FNA Tg was concordant with positive cytology in all patients with DTC and may serve as a useful tool in patients with negative and nondiagnostic cytology to guide surgical management. PMID- 27186555 TI - Current practices in the diagnosis and management of gestational diabetes mellitus in India (WINGS-5). AB - AIM: To obtain information on existing practices in the diagnosis and management of gestational diabetes mellitus (GDM) among physicians/diabetologists/endocrinologists and obstetricians/gynecologists (OB/GYNs) in India. METHODS: Details regarding diagnostic criteria used, screening methods, management strategies, and the postpartum follow-up of GDM were obtained from physicians/diabetologists/endocrinologists and OB/GYNs across 24 states of India using online/in-person surveys using a structured questionnaire. RESULTS: A total of 3841 doctors participated in the survey of whom 68.6% worked in private clinics. Majority of OB/GYNs (84.9%) preferred universal screening for GDM, and screening in the first trimester was performed by 67% of them. Among the OB/GYNs, 600 (36.7%) reported using the nonfasting 2 h criteria for diagnosing GDM whereas 560 (29.4%) of the diabetologists/endocrinologists reported using the same. However, further questioning on the type of blood sample collected and the glucose load used revealed that, in reality, only 208 (12.7%) and 72 (3.8%), respectively, used these criteria properly. The survey also revealed that the International Association of Diabetes and Pregnancy Study Groups criteria was followed properly by 299 (18.3%) of OB/GYNs and 376 (19.7%) of physicians/diabetologists/endocrinologists. Postpartum oral glucose tolerance testing was advised by 56% of diabetologists and 71.6% of OB/GYNs. CONCLUSION: More than half of the physicians/diabetologists/endocrinologists and OB/GYNs in India do not follow any of the recommended guidelines for the diagnosis of GDM. This emphasizes the need for increased awareness about screening and diagnosis of GDM both among physicians/diabetologists/endocrinologists and OB/GYNs in India. PMID- 27186556 TI - Insulin degludec aspart: One-year real world experience. AB - BACKGROUND: This retrospective analysis describes the use of insulin degludec aspart (IDegAsp) in India. MATERIAL AND METHODS: All subjects who had received IDegAsp for 52 weeks at two endocrine centers were included in this study. RESULTS: Forty-eight subjects (40 men), with mean age of 54.33 +/- 9.63 years and mean duration of diabetes of 6.33 +/- 2.96 years, started IDegAsp as insulin of initiation (16), as an intensification regime (4), as de-escalation from basal bolus therapy (16), or as switch from premixed insulin (12). The dose of IDegAsp fell from 43.17 +/- 21.18 U/day or 0.56 +/- 0.23 U/kg to 37.75 +/- 17.13U/day (0.51 +/- 0.12 U/kg) at 24 weeks and 41.41 +/- 15.33 U/day (0.56 +/- 0.17 U/kg) at 52 weeks. Hemoglobin A1c (HbA1c), which was 9.52 +/- 1.27% at the start of therapy, fell to 7.51 +/- 0.46% at 26 weeks and to 7.48 +/- 0.40% at 52 weeks. Fasting plasma glucose fell from 154.08 +/- 33.30 mg% to 108.58 +/- 22.26 mg% at 26 weeks and 102.17 +/- 12.79 mg% at 52 weeks. Of the 48 subjects, 39 (81.25%) achieved a target of HbA1c <7.0% at both 26 and 52 weeks. No episode of hypoglycemia was reported in the 4 weeks preceding the analysis. CONCLUSION: This communication highlights the efficacy, safety, and tolerability, while providing insight into the usage patterns of IDegAsp. PMID- 27186558 TI - Association of type 1 diabetes mellitus and autoimmune disorders in Brazilian children and adolescents. AB - CONTEXT: Type 1 diabetes mellitus (T1DM) is caused by an immune-mediated destruction of pancreatic beta cells. Other autoimmune diseases can be observed in association with T1DM. The screening for celiac disease (CD) and Hashimoto's thyroiditis is necessary due to the increased prevalence of these pathologies in T1DM patients. AIMS: This study aimed to investigate the prevalence of autoimmune markers for pancreatitis, thyroiditis, and CD in racially admixtured children and adolescents with T1DM. SETTINGS AND DESIGN: Cross-sectional clinic-based study. METHODS: Seventy-one patients with T1DM (average: 11.6 +/- 5.1 years). In all patients, the following antibodies were surveyed: Anti-glutamic acid decarboxylase (anti-GAD), immunoglobulin A (IgA) anti-transglutaminase (anti tTG), Antithyroglobulin (AAT), anti-thyroid peroxidase (anti-TPO), and IgA. STATISTICAL ANALYSIS USED: The quantitative variables were expressed as a mean and standard deviation and the qualitative variables in contingency tables. Student's t-test and chi(2) tests were used to assess the differences between the groups. The level of significance was established as P < 0.05. RESULTS: The prevalence of anti-GAD antibodies was 5.9%; anti-tTG IgA, 7.4%; anti-TPO, 11.8%; and AAT, 11.8%. CONCLUSIONS: Children and adolescents with T1DM have increased the prevalence of antithyroid and CD-related antibodies. The positivity for anti GAD and antithyroid antibodies was less frequent than in other studies. The prevalence of anti-tTG antibodies was similar to the literature. PMID- 27186557 TI - Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus from India. AB - BACKGROUND: This post hoc analysis evaluated the efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus (T2DM) from India. METHODS: Changes from baseline in HbA1c, fasting plasma glucose (FPG), body weight, and blood pressure (BP) with canagliflozin 100 and 300 mg were evaluated in a subgroup of patients from India (n = 124) from 4 randomized, double-blind, placebo- and active-controlled, Phase 3 studies (N = 2313; Population 1). Safety was assessed based on adverse event (AE) reports in these patients and in a broader subgroup of patients from India (n = 1038) from 8 randomized, double-blind, placebo- and active-controlled, Phase 3 studies (N = 9439; Population 2). RESULTS: Reductions in HbA1c with canagliflozin 100 and 300 mg were -0.74% and -0.88%, respectively, in patients from India, and -0.81% and -1.00%, respectively, in the 4 pooled Phase 3 studies. In the Indian subgroup, both canagliflozin doses provided reductions in FPG, body weight, and BP that were consistent with findings in the overall population. The incidence of overall AEs in patients from India was generally similar with canagliflozin 100 and 300 mg and noncanagliflozin. The AE profile in patients from India was generally similar to the overall population, with higher rates of genital mycotic infections and osmotic diuresis-related and volume depletion related AEs with canagliflozin versus noncanagliflozin. CONCLUSION: Canagliflozin provided glycemic control, body weight reduction, and was generally well tolerated in patients with T2DM from India. PMID- 27186559 TI - Prevalence of hypothyroidism in pregnancy: An epidemiological study from 11 cities in 9 states of India. AB - BACKGROUND: A previous hospital based study from Delhi revealed a high prevalence of hypothyroidism in pregnant women. Several other studies with small sample size also indicate a rising trend of prevalence of hypothyroidism during pregnancy in India. OBJECTIVE: To assess prevalence of hypothyroidism in pregnant women from various states/cities across India. MATERIALS AND METHODS: This was a cross sectional multicenter study conducted at Allahabad (Uttar Pradesh), Bengaluru (Karnataka), Chennai (Tamil Nadu), Kolkata (West Bengal), Hyderabad (Telangana), Nasik (Maharashtra), Rohtak (Haryana), Pune (Maharashtra), New Delhi (Delhi), Srinagar (Kashmir), and Vizag (Andhra Pradesh) enrolling 2599 pregnant women. Estimation of thyroid stimulating hormone (TSH), free T4, and antithyroid peroxidase (TPO) antibodies was carried out using Roche modular kit using ECLIA technology in a central laboratory. RESULTS: We found in our study population that 13.13% of pregnant women have hypothyroidism (n = 388), using a cutoff TSH level of 4.5 MUIU/ml. This prevalence was much higher using the American Thyroid Association criteria. Anti-TPO antibodies were positive in 20.74% of all pregnant women (n = 613), whereas 40% (n = 155) of hypothyroid pregnant women were positive for anti-TPO antibodies. CONCLUSION: This study concludes that there is a high prevalence of hypothyroidism (13.13%), majority being subclinical in pregnant women during the first trimester from India and universal screening of hypothyroidism may be desirable in our country. PMID- 27186560 TI - Vitamin D supplementation reduces thyroid peroxidase antibody levels in patients with autoimmune thyroid disease: An open-labeled randomized controlled trial. AB - BACKGROUND AND AIMS: Although Vitamin D deficiency has been linked to autoimmune thyroid disorders (AITD), the impact of Vitamin D supplementation on thyroid autoimmunity is not known. This study aimed to evaluate the impact of Vitamin D supplementation on thyroid autoimmunity (thyroid peroxidase antibody [TPO-Ab] titers) in patients with newly diagnosed AITD in a randomized controlled trial. MATERIALS AND METHODS: One hundred two patients with newly diagnosed AITD (TPO-Ab > 34 kIU/L and/or sonographic evidence of thyroiditis) patients were randomized into Group-1 (intervention group) and Group-2 (control group). Group-1 received cholecalciferol 60,000 IU weekly and calcium 500 mg/day for 8 weeks; Group-2 received calcium 500 mg/day for 8 weeks. Responders were defined as >=25% fall in TPO-Ab titers. Individuals with at least 3-month follow-up were analyzed. Trial is registered at ctri.nic.in (CTRI/2015/04/005713). RESULTS: Data from 100 AITD patients (68 with thyroid stimulating hormone [TSH] <=10 mIU/L, 32 with TSH > 10 mIU/L), 93% having Vitamin D insufficiency, were analyzed. TPO-Ab titers were highest among patients in the lowest 25-hydroxyvitamin D quartile (P = 0.084). At 3 months follow-up, there was significant fall in TPO-Ab in Group-1 (-46.73%) as compared to Group-2 (-16.6%) (P = 0.028). Sixty-eight percentage patients in Group-1 were responders compared to 44% in Group-2 (P = 0.015). Kaplan-Meier analysis revealed significantly higher response rate in Group-1 (P = 0.012). Significantly greater reduction in TPO-Ab titers was observed in AITD with TSH <= 10 mIU/L compared to TSH > 10 mIU/L. Cox regression revealed Group-1 followed by TPO-Ab and free tetraiodothyronine levels to be a good predictor of response to therapy (P = 0.042, 0.069, and 0.074, respectively). CONCLUSION: Vitamin D supplementation in AITD may have a beneficial effect on autoimmunity as evidence by significant reductions in TPO-Ab titers. PMID- 27186561 TI - Bilateral inferior petrosal sinus sampling using vasopressin. AB - CONTEXT: Anatomical localization of pituitary adenoma can be challenging in adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome, and bilateral inferior petrosal sinus sampling (BIPSS) is considered gold standard in this regard. Stimulation using corticotrophin-releasing hormone (CRH) improves the sensitivity of BIPSS, however, same is not easily available in India. Therefore, we undertook this study of BIPPS using vasopressin as agent for stimulation owing to its ability to stimulate V3 receptors present on corticotrophs. AIMS: To study the tumor localization and lateralization in difficult to localize cases of ACTH dependent Cushing's syndrome by bilateral inferior petrosal sinus sampling using vasopressin for corticotroph stimulation. SETTINGS AND DESIGN: Prospective observational study. SUBJECTS AND METHODS: Six patients (5 females) meeting inclusion criteria underwent BIPSS using vasopressin for stimulation. RESULTS: All six patients had nonsuppressible overnight and low dose dexamethasone suppression test with elevated plasma ACTH levels suggestive of ACTH-dependent Cushing's syndrome. High dose dexamethasone suppression test showed suppressible cortisol in two cases, and microadenoma was seen in two patients on magnetic resonance imaging pituitary. Contrast enhanced computed tomography of the abdomen showed left adrenal hyperplasia in one case and anterior mediastinal mass with bilateral adrenal hyperplasia another. Using BIPSS four patients were classified as having Cushing's disease that was confirmed histopathologically following surgery. Of the remaining two, one had primary pigmented nodular adrenocortical disease, and another had thymic carcinoid with ectopic ACTH production as the cause of Cushing's syndrome. No serious adverse events were noted. CONCLUSIONS: Vasopressin may be used instead of CRH and desmopressin for stimulation in BIPSS. PMID- 27186562 TI - The Mahabharata and reproductive endocrinology. AB - This communication approaches the Mahabharata through the prism of reproductive endocrinology. Descriptions of episodes related to reproduction are listed here, to provide fodder for the endocrinologically minded brain. The cases described here are perhaps, the first documented observations of fetal orgasm, pseudocyesis and assisted reproductive technology, including assisted insemination by donor, induction of ovulation, and in vitro fertilization as well as precocious growth and intersex. We do not presume to offer a definite explanation for these interesting episodes from the Mahabharata. We do, however, hope to stimulate interest in ancient Indian literature, and encourage a literary "forensic endocrine" analysis of events relevant to our specialty. PMID- 27186563 TI - Flexibility in insulin prescription. AB - This communication explores the concept of flexibility, a propos insulin preparations and insulin regimes used in the management of type 2 diabetes. The flexibility of an insulin regime or preparation is defined as their ability to be injected at variable times, with variable injection-meal time gaps, in a dose frequency and quantum determined by shared decision making, with a minimal requirement of glucose monitoring and health professional consultation, with no compromise on safety, efficiency and tolerability. The relative flexibility of various basal, prandial and dual action insulins, as well as intensive regimes, is compared. The biopsychosocial model of health is used to assess the utility of different insulins while encouraging a philosophy of flexible insulin usage. PMID- 27186564 TI - National List of Essential Medicines, 2015: Endocrinology perspective. PMID- 27186565 TI - HbA1c for diabetes screening in acute coronary syndrome: National Institute for Health and Care Excellence criteria and universal screening. PMID- 27186566 TI - Determination of the potency of a novel saw palmetto supercritical CO2 extract (SPSE) for 5alpha-reductase isoform II inhibition using a cell-free in vitro test system. AB - BACKGROUND: The nicotinamide adenine dinucleotide phosphate-dependent membrane protein 5alpha-reductase catalyses the conversion of testosterone to the most potent androgen - 5alpha-dihydrotestosterone. Two 5alpha-reductase isoenzymes are expressed in humans: type I and type II. The latter is found primarily in prostate tissue. Saw palmetto extract (SPE) has been used extensively in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH). The pharmacological effects of SPE include the inhibition of 5alpha-reductase, as well as anti-inflammatory and antiproliferative effects. Clinical studies of SPE have been inconclusive - some have shown significant results, and others have not - possibly the result of varying bioactivities of the SPEs used in the studies. PURPOSE: To determine the in vitro potency in a cell-free test system of a novel SP supercritical CO2 extract (SPSE), an inhibitor of the 5alpha-reductase isoenzyme type II. MATERIALS AND METHODS: The inhibitory potency of SPSE was compared to that of finasteride, an approved 5alpha-reductase inhibitor, on the basis of the enzymatic conversion of the substrate androstenedione to the 5alpha-reduced product 5alpha-androstanedione. RESULTS: By concentration-dependent inhibition of 5alpha-reductase type II in vitro (half-maximal inhibitory concentration 3.58+/-0.05 MUg/mL), SPSE demonstrated competitive binding toward the active site of the enzyme. Finasteride, the approved 5alpha-reductase inhibitor tested as positive control, led to 63%-75% inhibition of 5alpha-reductase type II. CONCLUSION: SPSE effectively inhibits the enzyme that has been linked to BPH, and the amount of extract required for activity is comparatively low. It can be confirmed from the results of this study that SPSE has bioactivity that promotes prostate health at a level that is superior to that of many other phytotherapeutic extracts. The bioactivity of SPSE corresponds favorably to that reported for the hexane extract used in a large number of positive BPH clinical trials, as well as to finasteride, the established standard of therapy among prescription drugs. Future in vitro and clinical trials involving SPEs would be useful for elucidating their comparative differences, as well as appropriate patient selection for their use. PMID- 27186567 TI - A comparative study of postoperative pain for open thyroidectomy versus bilateral axillo-breast approach robotic thyroidectomy using a self-reporting application for iPad. AB - PURPOSE: Postoperative pain for robotic thyroid surgeries including bilateral axillo-breast approach (BABA) has not been well studied. In this study, we have developed a self-reporting application (SRA) for iPad and prospectively collected pain scores from open thyroidectomy (OT) and BABA robotic thyroidectomy (RT) patients. METHODS: Female patients who underwent total thyroidectomy for papillary thyroid carcinoma were included. Patients recorded pain scores for throat, anterior neck, posterior neck, chest, and back on postoperative days 1, 2, and 3. Once discharged, on postoperative day 14, a survey was also conducted on satisfaction of SRA and cosmesis. RESULTS: A total of 54 patients were enrolled (27 BABA RT and 27 OT). There were no significant differences between the 2 groups in clinicopathological characteristics and postoperative complication rates. Postoperative pain scores at days 1, 2, 3, and 14 were not significantly different between the groups for throat, anterior neck, posterior neck, or back. Postoperative analgesic requirements were similar between the 2 groups. Wound satisfaction scores were significantly higher in the BABA RT group (BABA RT 7.4 vs. OT 5.7; P = 0.016). Satisfaction scores for the usefulness of SRA were above 7.2 for all four questionnaire items on the 10-point scale. CONCLUSION: Postoperative pain for BABA RT is equivalent to OT but offers greater cosmetic satisfaction for patients. A mobile device application such as SRA may facilitate proper assessment and management of pain in postoperative patients. PMID- 27186568 TI - The rat choledochojejunostomy model for microsurgical training. AB - PURPOSE: The feasibility of a rat choledochojejunostomy (CJ) training model was investigated, as an introductory model to microsurgery for general surgeons. METHODS: Roux-en-Y CJ was performed on 20 rats. Interrupted 10-0 prolene sutures were used to perform CJ. The animals were observed for 7 days and sacrificed and examined. RESULTS: The rats were divided into 2 groups of 10 based on surgical order. The CJ time showed a significant decrease from 36.2 +/- 5.6 minutes in group 1 to 29.4 +/- 5.7 minutes in group 2 (P = 0.015). The bile leakage rate was 40% in group 1 and 10% in group 2. The survival time was 5.4 +/- 2.2 days in group 1 and 7 days in group 2 (P = 0.049). CONCLUSION: The rat CJ training model is a feasible introductory model for general surgeons with no previous experience in microsurgery. PMID- 27186569 TI - Prognostic significance of intraoperative macroscopic serosal invasion finding when it shows a discrepancy in pathologic result gastric cancer. AB - PURPOSE: Depth of wall invasion is an important prognostic factor in patients with gastric cancer, whereas the prognostic significance of intraoperative macroscopic serosal invasion (mSE) findings remain unclear when they show a discrepancy in pathologic findings. This study, therefore, assessed the prognostic significance of mSE. METHODS: Data from cohort of 2,835 patients with resectable gastric cancer who underwent surgery between 1990 and 2010 were retrospectively reviewed. RESULTS: The overall accuracy of mSE and pathologic results was 83.4%. The accuracy of mSE was 75.5% in pT2. On the other hand, the accuracy of pT3 dropped to 24.5%. According to mSE findings (+/-), the 5-year disease-specific survival (DSS) rate differed significantly in patients with pT2 (+; 74.2% vs. -; 92.0%), pT3 (+; 76.7% vs. -; 91.8%) and pT4a (+; 51.3% vs. -; 72.8%) (P < 0.001 each), but not in patients with T1 tumor. Multivariate analysis showed that mSE findings (hazard ratio [HR], 2.275; 95% confidence interval [CI], 1.148-4.509), tumor depth (HR, 6.894; 95% CI, 2.325-20.437), nodal status (HR, 5.206; 95% CI, 2.298-11.791), distant metastasis (HR, 2.881; 95% CI, 1.388 6.209), radical resection (HR, 2.002; 95% CI, 1.017-3.940), and lymphatic invasion (HR, 2.713; 95% CI, 1.424-5.167) were independent predictors of 5-year DSS rate. CONCLUSION: We observed considerable discrepancies between macroscopic and pathologic diagnosis of serosal invasion. However, macroscopic diagnosis of serosal invasion was independently prognostic of 5-year DSS. It suggests that because the pathologic results could not be perfect and the local inflammatory change with mSE(+) could affect survival, a combination of mSE(+/-) and pathologic depth may be predictive of prognosis in patients with gastric cancer. PMID- 27186570 TI - Risk factors for cancer recurrence or death within 6 months after liver resection in patients with colorectal cancer liver metastasis. AB - PURPOSE: The aim of this study was to find risk factors for early recurrence (ER) and early death (ED) after liver resection for colorectal cancer liver metastasis (CRCLM). METHODS: Between May 1990 and December 2011, 279 patients underwent liver resection for CRCLM at Korea University Medical Center. They were assigned to group ER (recurrence within 6 months after liver resection) or group NER (non ER; no recurrence within 6 months after liver resection) and group ED (death within 6 months after liver resection) or group NED (alive > 6 months after liver resection). RESULTS: The ER group included 30 patients (10.8%) and the NER group included 247 patients (89.2%). The ED group included 18 patients (6.6%) and the NED group included 253 patients (93.4%). Prognostic factors for ER in a univariate analysis were poorly differentiated colorectal cancer (CRC), synchronous metastasis, >=5 cm of liver mass, >=50 ng/mL preoperative carcinoembryonic antigen level, positive liver resection margin, and surgery alone without perioperative chemotherapy. Prognostic factors for ED in a univariate analysis were poorly differentiated CRC, positive liver resection margin, and surgery alone without perioperative chemotherapy. Multivariate analysis showed that poorly differentiated CRC, >=5-cm metastatic tumor size, positive liver resection margin, and surgery alone without perioperative chemotherapy were independent risk factors related to ER. For ED, poorly differentiated CRC, positive liver resection margin, and surgery alone without perioperative chemotherapy were risk factors in multivariate analysis. CONCLUSION: Complete liver resection with clear resection margin and perioperative chemotherapy should be carefully considered when patients have the following preoperative risk factors: metastatic tumor size >= 5 cm and poorly differentiated CRC. PMID- 27186571 TI - Early results with the Mutaf technique: a novel off-midline approach in pilonidal sinus surgery. AB - PURPOSE: The objective of the present study was to compare different off-midline techniques in terms of their advantages and disadvantages. METHODS: A total of 81 patients were included in this prospective, controlled, randomized study. Patients in group 1 were treated with the Limberg flap, and patients in group 2 were treated with Mutaf technique. Patients were followed up for 9 months postsurgically and assessed at regular intervals. RESULTS: A total of 41 and 40 patients received surgical treatment with Limberg or Mutaf techniques, respectively. The 2 groups were similar in terms of age, gender, body mass index, and Tezel pilonidal sinus classification. Also, the 2 groups were comparable with regard to the frequency of preoperative discharge from the wound site, history of abscess formation, and the resultant antibiotic use. Early results showed similar recurrence rates and surgical-site complications between the 2 groups. Although a lower visual analogue scale score was found in group 2 at postoperative day 1, seroma persistence, time to withdrawal of surgical drains, and wound healing were more prolonged. CONCLUSION: In this study, Mutaf technique was comparable to Limberg flap in the treatment of pilonidal sinus. Therefore, Mutaf technique may be offered as a viable surgical therapeutic option among off-midline closure approaches. PMID- 27186572 TI - Balloon-assisted maturation for arteriovenous fistula maturation failure: an early period experience. AB - PURPOSE: Balloon-assisted maturation (BAM) is emerging as a salvage management for arteriovenous fistula maturation failure (AVF MF). However, BAM is a relatively new, yet controversial technique for AVF maturation. Therefore, we evaluated the effectiveness of BAM for AVF MF. METHODS: Between January 2012 and December 2014, 249 AVFs were created. The total MF rate was 24.8%. But, only 110 AVFs were enrolled, including 74 brachiocephalic (BC) AVFs and 36 radiocephalic (RC) AVFs. The follow-up period was 12 months. Among those, there were 42 MFs (22 BC AVFs and 20 RC AVFs) and 68 maturation successes (MS) (52 BC AVFs and 16 RC AVFs). BAM was involved in MF group. We compared the clinical characteristics, AVF flows, and AVF flow ratios of MF and MS groups. Also, we evaluated the etiology, management, and result of MF. RESULTS: There was no difference in clinical characteristics between MF and MS groups. In MF group, 39 balloon angioplasties (BAs) for 42 AVF MFs were performed. Number of BA was 1.45 +/- 0.57 and duration of BA was 21.30 +/- 21.24 weeks. BAM rate was 46.2%. For 1 year after AVF creation, AVF flows of MS group were significantly larger than those of MF group (P < 0.05) but there was no difference in AVF flow ratio between MF and MS groups (P > 0.05). CONCLUSION: BA for AVF MF is a relatively applicable and effective modality. Although a large volume study is necessary, we suggest BAM is an effective salvage management for AVF MF. PMID- 27186573 TI - Intraoperative indocyanine green angiography for the objective measurement of blood flow. AB - PURPOSE: Intraoperative assessment of tissue perfusion is important to predict wound healing or improvement of symptoms in patients with peripheral arterial disease (PAD) or vascular trauma. There is no widely accepted standard for intraoperative measurement of tissue perfusion. Here, we report the use of indocyanine green (ICG)-based angiography to determine the blood flow in patients with PAD and vascular trauma. METHODS: The SPY fluorescent imaging system was utilized. A dose of 3-5 mL of ICG (2.5 mg/mL) was injected intravenously followed by a 10 mL normal saline flush. The SPY imaging system was used to quantitatively assess perfusion. During the study period, the SPY imaging system was applied in 4 patients with PAD and one patient with vascular trauma. RESULTS: In 3 patients with PAD associated with an ischemic wound, complete wound healing was achieved with the indication of viable tissue by the SPY system. In one patient with severe claudication in both lower extremities, the ICG angiography was used to determine the increased blood flow after revascularization. In the case of vascular trauma, this imaging system enabled the delineation of viability of the injured tissue. CONCLUSION: ICG angiography can determine the surface tissue viability in PAD patients. In cases of severe vascular trauma,the SPY system can be used to determine tissue perfusion. Further study is warranted to define the definite utility of this technology to assess perfusion, response to revascularization, and potentially, to predict the likelihood of wound healing. PMID- 27186574 TI - Associating microwave ablation and portal vein ligation for staged hepatectomy for the treatment of huge hepatocellular carcinoma with cirrhosis. AB - Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) could induce extensive and rapid future liver remnant hypertrophy. However, the morbidity for ALPPS is very high. This paper reports a modified ALPPS (associating microwave ablation and portal vein ligation for staged hepatectomy, AMAPS), which was successfully applied in the treatment of huge hepatocellular carcinoma with cirrhosis, and the procedure of operation was greatly simplified. Hence, AMAPS is feasible and safe in selected patients with primary hepatocellular carcinoma and cirrhosis. PMID- 27186575 TI - IgG4-related disease of the rectum. AB - IgG4-related disease is a relatively new disease entity characterized by elevated serum IgG4 levels and marked infiltration of IgG4-positive plasma cells in lesions. Organ enlargement or nodular lesions consisting of abundant infiltration of lymphocytes and IgG4-positive plasma cells and fibrosis are seen in various organs throughout. We encountered a patient with an inflammatory pseudotumor of the rectum, which was histopathologically confirmed to be an IgG4-related disease. The patient was a 28-year-old woman who had constipation for 3 months. The endoluminal ultrasonography showed a lesion that was heterogeneous and low echogenic in lower rectum. The result of colonoscopic biopsy findings was of chronic proctitis with lymphoid aggregates. For a confirmative diagnosis, excision was performed. Histopathological examination represented plasma cell infiltration and fibrosis. Immunohistochemistry revealed prominence of IgG4 positive plasma cells and confirmed the diagnosis of IgG4-related disease. The patient is currently under observation on low-dose oral prednisolone without relapse. PMID- 27186576 TI - Probable Buruli Ulcer Disease in Honduras. PMID- 27186577 TI - Acute Kidney Injury Is Common in Pediatric Severe Malaria and Is Associated With Increased Mortality. AB - Background. Acute kidney injury (AKI) is a well recognized complication of severe malaria in adults, but the incidence and clinical importance of AKI in pediatric severe malaria (SM) is not well documented. Methods. One hundred eighty children aged 1 to 10 years with SM were enrolled between 2011 and 2013 in Uganda. Kidney function was monitored daily for 4 days using serum creatinine (Cr). Acute kidney injury was defined using the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Blood urea nitrogen (BUN) and Cr were assessed using i-STAT, and cystatin C (CysC) was measured by enzyme-linked immunosorbent assay. Results. Eighty-one (45.5%) children had KDIGO-defined AKI in the study: 42 (51.9%) stage 1, 18 (22.2%) stage 2, and 21 (25.9%) stage 3. Acute kidney injury evolved or developed in 50% of children after admission of hospital. There was an increased risk of AKI in children randomized to inhaled nitric oxide (iNO), with 47 (54.0%) of children in the iNO arm developing AKI compared with 34 (37.4%) in the placebo arm (relative risk, 1.36; 95% confidence interval [CI], 1.03-1.80). Duration of hospitalization increased across stages of AKI (P = .002). Acute kidney injury was associated with neurodisability at discharge in the children receiving placebo (25% in children with AKI vs 1.9% in children with no AKI, P = .002). Mortality increased across stages of AKI (P = .006) in the placebo arm, reaching 37.5% in stage 3 AKI. Acute kidney injury was not associated with neurodisability or mortality at discharge in children receiving iNO (P > .05 for both). Levels of kidney biomarkers were predictive of mortality with areas under the curves (AUCs) of 0.80 (95% CI, .65-.95; P = .006) and 0.72 (95% CI, .57-.87; P < .001), respectively. Admission levels of CysC and BUN were elevated in children who died by 6 months (P < .0001 and P = .009, respectively). Conclusions. Acute kidney injury is an underrecognized complication in young children with SM and is associated with increased mortality. PMID- 27186578 TI - Detection of Bacteriuria by Canine Olfaction. AB - Background. Urinary tract infections (UTIs) are a significant medical problem , particularly for patients with neurological conditions and the elderly. Detection is often difficult in these patients, resulting in delayed diagnoses and more serious infections such as pyelonephritis and life-threatening sepsis. Many patients have a higher risk of UTIs because of impaired bladder function, catheterization, and lack of symptoms. Urinary tract infections are the most common nosocomial infection; however, better strategies are needed to improve early detection of the disease. Methods. In this double-blinded, case-control, validation study, we obtained fresh urine samples daily in a consecutive case series over a period of 16 weeks. Dogs were trained to distinguish urine samples that were culture-positive for bacteriuria from those of culture-negative controls, using reward-based clicker and treat methods. Results. Samples were obtained from 687 individuals (from 3 months to 92 years of age; 86% female and 14% male; 34% culture-positive and 66% culture-negative controls). Dogs detected urine samples positive for 100 000 colony-forming units/mL Escherichia coli (N = 250 trials; sensitivity 99.6%, specificity 91.5%). Dilution of E coli urine with distilled water did not affect accuracy at 1% (sensitivity 100%, specificity 91.1%) or 0.1% (sensitivity 100%, specificity 93.6%) concentration. Diagnostic accuracy was similar to Enterococcus (n = 50; sensitivity 100%, specificity 93.9%), Klebsiella (n = 50; sensitivity 100%, specificity 95.1%), and Staphylococcus aureus (n = 50; sensitivity 100%, specificity 96.3%). All dogs performed with similarly high accuracy: overall sensitivity was at or near 100%, and specificity was above 90%. Conclusions. Canine scent detection is an accurate and feasible method for detection of bacteriuria. PMID- 27186579 TI - Pre-existence and Persistence of Resistant Minority Hepatitis C Virus Variants in Genotype 1-Infected Patients Treated With Simeprevir/Peginterferon/Ribavirin. AB - Background. The pre-existence of minority hepatitis C virus (HCV) variants and their impact on treatment outcome, as well as the persistence of emerging resistant variants posttreatment in patients failing treatment with simeprevir/peginterferon/ribavirin (SMV/PR), were assessed by deep sequencing (DS). Methods. Population sequencing (PS) and Illumina DS were performed on HCV genotype 1 isolates from patients treated with SMV/PR in Phase 2b (PILLAR [NCT00882908] and ASPIRE [NCT00980330]) and Phase 3 (QUEST-1 [NCT01289782], QUEST 2 [NCT01290679], and PROMISE [NCT01281839]) trials. Results. Minority polymorphisms (ie, detected pretreatment by DS only) reducing SMV activity in vitro were uncommon (3.6%, 19 of 534 patients). These SMV-resistant minority polymorphisms were detected in similar proportions of patients achieving (3.7%) and not achieving (3.3%) sustained virologic response with SMV/PR and generally did not emerge as major variants at time of failure. SMV-resistant variants emerging at time of failure were no longer detected at end of study in 69.3% and 52.0% of the patients by PS and DS, respectively. Conclusions. Minority polymorphisms did not impact outcome of SMV/PR treatment. The majority of emerging variants that became undetectable at end of study by PS were also undetectable by DS. These results suggest no added value of DS for clinical usage of SMV. PMID- 27186580 TI - Novel Highly Pathogenic Avian H5 Influenza A Viruses in Live Poultry Markets, Wuxi City, China, 2013-2014. AB - During 12 recent months of periodic influenza virus surveillance at 9 live poultry markets in Wuxi City China, we identified multiple highly pathogenic H5N6, H5N8, H5N2, and H5N1 avian influenza viruses. The variety of potentially pandemic viruses in this low-risk area is disconcerting and portends an increased pandemic threat. PMID- 27186581 TI - Cryptococcal Antigenemia in Nigerian Patients With Advanced Human Immunodeficiency Virus: Influence of Antiretroviral Therapy Adherence. AB - Background. Cryptococcal meningitis has a high mortality in human immunodeficiency virus (HIV)-infected persons in Africa. This is preventable with early screening and preemptive therapy. We evaluated the prevalence of cryptococcal disease by antigen testing, possible associated factors, and outcomes in HIV-infected patients being managed in a tertiary hospital in Lagos, Nigeria. Methods. Sera were collected from 214 consenting HIV-infected participants with CD4(+) counts <250 cells/mm(3), irrespective of their antiretroviral therapy (ART) status, between November 2014 and May 2015. A cryptococcal antigen (CrAg) lateral flow assay was used for testing. Pertinent clinical data were obtained from patients and their case notes. Results. Of the 214 participants, females (124; 57.9%) outnumbered males. Mean age was 41.3 +/- 9.4 (standard deviation) years. The majority (204; 95.3%) were ART experienced. The median CD4(+) cell count was 160 cells/mm(3) (interquartile range, 90-210). The overall seroprevalence of cryptococcal antigenemia was 8.9% (19 of 214); 6 of 61 (9.8%) in those with CD4(+) cell counts <100 cells/mm(3), 4 of 80 (5.0%) in the 100-200 group, and 9 of 73 (12.3%) in 200-250 cells/mm(3) group. Among ART naive patients, 1 of 10 (10%) was CrAg positive. Twenty-seven of 214 (12.6%) had associated oral thrush. Potential baseline meningitis symptoms (3 of 214 [1.4%] experienced neck pain or stiffness and 21 of 214 [9.8%] experienced headache) were common in the study group, but the result was not statistically significant in relation to CrAg positivity. Two of 19 (10.5%) CrAg-positive patients died, 10 of 19 (52.6%) were lost to follow up, and 7 of 19 (36.8%) were alive. Empirical fluconazole was routinely given to those with low CD4 counts <100 cells/mm(3), which was unrelated to CrAg positivity (P = .018). Conclusions. We report a prevalence of 8.9% cryptococcal antigenemia in a setting where first-line antifungals are not readily available. We recommend CrAg screening for HIV infected patients, even for patients on ART. PMID- 27186583 TI - Infectious Diseases (ID) Learning Unit: How Rapidly to Evaluate for Active Tuberculosis Disease in Low-Prevalence Settings. AB - With declining tuberculosis (TB) incidence in low-prevalence settings, many clinicians are likely unaware that the approach to diagnosing active TB is evolving with newer technologies. Rapid molecular assays are commercially available, and more are likely to enter the market in the coming years. These tests, such as the Xpert MTB/RIF, which can detect TB and drug-resistance in 2 hours, are increasingly used in settings with higher TB prevalence; however, uptake has been slower in low-prevalence settings. Newer algorithms incorporating rapid TB diagnostics have the ability to alter current clinical and infection control practice patterns. In this learning unit, we review current and newly available tests for the detection of active TB disease and their usage in low prevalence settings. PMID- 27186582 TI - Shedding of Hepatitis C Virus in Semen of Human Immunodeficiency Virus-Infected Men. AB - Background. The epidemic of sexually transmitted hepatitis C virus (HCV) infection among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) has been documented for over a decade. Despite this, there is no consensus as to the risk factors for sexual acquisition of HCV in these men. Methods. We obtained paired semen and blood samples at 2-week intervals from HIV infected MSM with recent and chronic HCV infection and quantified HCV in semen. Results. Hepatitis C virus was quantified in 59 semen specimens from 33 men. Hepatitis C virus was shed in 16 (27%) of semen specimens from 11 (33%) of the men. Median HCV viral load (VL) in semen was 1.49 log10 IU/mL. Hepatitis C virus VL in blood was significantly higher at the time of HCV shedding in semen than when HCV shedding in semen was not detected (P = .002). Furthermore, there was a significant correlation between the HCV VL in blood and semen overall (rs = 0.41; P = .001), and in the subgroup with recent HCV infection (rs = 0.37; P = .02), but not in the subgroup with chronic HCV infection (rs = 0.34; P = .1). Conclusions. One third of HIV-infected MSM coinfected with HCV shed HCV into their semen. Based on the HCV VL in semen in this study, an average ejaculate would deliver up to 6630 IU of virus into the rectum of the receptive partner. Therefore, our data strongly support that condoms should be used during anal intercourse among MSM to prevent transmission of HCV. PMID- 27186584 TI - Human Immunodeficiency Virus/Hepatitis C Virus Coinfection in Spain: Prevalence and Patient Characteristics. AB - Background. The purpose of this study was to assess the prevalence of anti hepatitis C virus (HCV) antibodies (Abs) and active HCV infection in human immunodeficiency virus (HIV)-infected (HIV+) patients in Spain in 2015. This was a cross-sectional study. Methods. The study was performed in 41 centers in 2015. Sample size was estimated for an accuracy of 2%, the number of patients from each hospital was determined by proportional allocation, and patients were selected using simple random sampling. Results. The reference population was 35 791 patients, and the sample size was 1867 patients. Hepatitis C virus serostatus was known in 1843 patients (98.7%). Hepatitis C virus-Abs were detected in 695 patients (37.7%), in whom the main route of HIV acquisition was injection drug use (75.4%). Of these 695 patients, 402 had HCV RNA, 170 had had a sustained viral response (SVR) after anti-HCV therapy, and 102 cleared HCV spontaneously. Hepatitis C virus-ribonucleic acid results were unknown in 21 cases. Genotype distribution (known in 367 patients) was 1a in 143 patients (39.0%), 4 in 90 (24.5%) patients, 1b in 69 (18.8%) patients, 3 in 57 (15.5%) patients, 2 in 5 (1.4%) patients, and mixed in 3 (0.8%) patients. Liver cirrhosis was present in 93 patients (23.1%) with active HCV infection and in 39 (22.9%) patients with SVR after anti-HCV therapy. Conclusions. The prevalence of HCV-Abs and active HCV infection in HIV+ patients in Spain is 37.7% and 22.1%, respectively; these figures are significantly lower than those recorded in 2002 and 2009. The predominant genotypes in patients with active HCV infection were 1a and 4. A high percentage of patients had cirrhosis. Cirrhosis is also common in patients with SVR after anti-HCV therapy. PMID- 27186585 TI - Risk of Cardiovascular Events Among Patients Initiating Efavirenz-Containing Versus Efavirenz-Free Antiretroviral Regimens. AB - Background. Efavirenz (EFV), an antiretroviral medication used to treat human immunodeficiency virus (HIV) infection, can increase lipid levels. Because hyperlipidemia is associated with increased risk for cardiovascular (CV) events, this study compared the risk of CV events in patients initiating EFV-containing vs EFV-free antiretroviral regimens. Methods. Antiretroviral-naive HIV-positive (HIV+) patients ages 18-64 were selected from commercial and Medicaid insurance claims databases. Patients with >=1 claim for antiretroviral medications between January 1, 2007 and December 31, 2013 were classified into 2 cohorts: EFV containing or EFV-free regimens. Patients were required to have 6 months of continuous enrollment before initiation, with no evidence of a CV event during this time. Patients were observed from initiation until the occurrence of a CV event, disenrollment, or study end. Cardiovascular events were identified through diagnosis or procedure codes for myocardial infarction, stroke, percutaneous coronary intervention, or coronary artery bypass graft. We calculated unadjusted incidence rates (IRs) and fit propensity-score-weighted Cox proportional hazards models. Results. There were 22 212 patients (11 978 EFV-containing and 10 234 EFV-free) identified in the commercial database and 7400 patients identified (2943 EFV-containing and 4457 EFV-free) in the Medicaid database. Cardiovascular events were rare (commercial IR = 396 per 100 000 person-years; Medicaid IR = 973 per 100 000 person-years). In propensity-score-weighted models, hazards of CV events were significantly lower for EFV-containing regimens in the commercial database (hazard ratio [HR] = 0.68; 95% confidence interval [CI], .49-.93) No significant difference was found in the Medicaid database (HR = 0.83; 95% CI, .58 1.19). Conclusions. This analysis found no evidence of increased risk of CV events among HIV+ patients initiating EFV-containing regimens. PMID- 27186586 TI - Delayed Diagnosis, Leprosy Reactions, and Nerve Injury Among Individuals With Hansen's Disease Seen at a United States Clinic. AB - Background. Hansen's disease (HD), or leprosy, is uncommon in the United States. We sought to describe the characteristics of patients with HD in a US clinic, including an assessment of delays in diagnosis and HD reactions, which have both been associated with nerve damage. Methods. A retrospective chart review was conducted on patients seen at an HD clinic in the southern United States between January 1, 2002 and January 31, 2014. Demographic and clinical characteristics were summarized, including delays in diagnosis, frequency of reactions, and other complications including peripheral neuropathy. Results. Thirty patients were seen during the study time period. The majority of patients were male (73%) and had multibacillary disease (70%). Brazil, Mexico, and the United States were the most frequent of the 14 countries of origin. Hansen's disease "reactions", severe inflammatory complications, were identified among 75% of patients, and nerve damage was present at diagnosis in 36% of patients. The median length of time between symptom onset and diagnosis was long at 12 months (range, 1-96), but no single factor was associated with a delay in diagnosis. Conclusions. The diagnosis of HD was frequently delayed among patients referred to our US clinic. The high frequency of reactions and neuropathy at diagnosis suggests that further efforts at timely diagnosis and management of this often unrecognized disease is needed to prevent the long-term sequelae associated with irreversible nerve damage. PMID- 27186587 TI - Measles Outbreak Associated With Low Vaccine Effectiveness Among Adults in Pohnpei State, Federated States of Micronesia, 2014. AB - Background. A measles outbreak in Pohnpei State, Federated States of Micronesia in 2014 affected many persons who had received >=1 dose of measles-containing vaccine (MCV). A mass vaccination campaign targeted persons aged 6 months to 49 years, regardless of prior vaccination. Methods. We evaluated vaccine effectiveness (VE) of MCV by comparing secondary attack rates among vaccinated and unvaccinated contacts after household exposure to measles. Results. Among 318 contacts, VE for precampaign MCV was 23.1% (95% confidence interval [CI], 425 to 87.3) for 1 dose, 63.4% (95% CI, -103 to 90.6) for 2 doses, and 95.9% (95% CI, 45.0 to 100) for 3 doses. Vaccine effectiveness was 78.7% (95% CI, 10.1 to 97.7) for campaign doses received >=5 days before rash onset in the primary case and 50.4% (95% CI, -52.1 to 87.9) for doses received 4 days before to 3 days after rash onset in the primary case. Vaccine effectiveness for most recent doses received before 2010 ranged from 51% to 57%, but it increased to 84% for second doses received in 2010 or later. Conclusions. Low VE was a major source of measles susceptibility in this outbreak; potential reasons include historical cold chain inadequacies or waning of immunity. Vaccine effectiveness of campaign doses supports rapid implementation of vaccination campaigns in outbreak settings. PMID- 27186588 TI - Salmonella enterica Subspecies diarizonae Maxillary Sinusitis in a Snake Handler: First Report. AB - In this study, we report the first case of reptile-associated maxillary sinusitis due to Salmonella enterica subspecies diarizonae in a snake handler and the third case of salmonella-associated sinusitis worldwide. The case highlights the potential of respiratory transmission and atypical salmonellosis presentations. PMID- 27186590 TI - The "100 Days Cough" Was Not Originally Whooping Cough. PMID- 27186589 TI - Implementation of Xpert MTB/RIF in Uganda: Missed Opportunities to Improve Diagnosis of Tuberculosis. AB - Background. The effect of Xpert MTB/RIF (Xpert) scale-up on patient outcomes in low-income settings with a high tuberculosis (TB) burden has not been established. We sought to characterize the effectiveness of Xpert as implemented across different levels of the healthcare system in Uganda. Methods. We reviewed laboratory records from 2012 to 2014 at 18 health facilities throughout Uganda. In 8 facilities, Xpert had been implemented onsite since 2012, and in 10 sites Xpert was available as an offsite referral test from another facility. We describe Xpert testing volumes by facility, Xpert and smear microscopy results, and downtime due to malfunction and cartridge stockouts. We compare TB treatment initiation as well as time to treatment between facilities implementing Xpert and those that did not. Results. The median number of Xpert assays run at implementing facilities was 25/month (interquartile range [IQR], 10-63), amounting to 8% of total capacity. Among 1251 assays run for a new TB diagnosis, 19% were positive. Among 1899 patients with smear-negative presumptive TB, the proportion starting TB treatment was similar between Xpert facilities (11%; 95% confidence interval [CI], 9%-13%) and non-Xpert facilities (9%; 95% CI, 8%-11%; P = .325). In Xpert facilities, a positive Xpert preceded TB treatment initiation in only 12 of 70 (17%) smear-negative patients initiated on treatment. Conclusions. Xpert was underutilized in Uganda and did not significantly increase the number of patients starting treatment for TB. Greater attention must be paid to appropriate implementation of novel diagnostic tests for TB if these new tools are to impact patient important outcomes. PMID- 27186591 TI - Idebenone for Leber's hereditary optic neuropathy. AB - Idebenone is a rapidly absorbed, safe and well-tolerated drug and is currently the only clinically proven treatment option for Leber's hereditary optic neuropathy (LHON) patients. Idebenone (Raxone(r)) is approved by the European Medicines Agency for the treatment of LHON and has been available on the European market since 2015. Due to its molecular mode of action of bypassing the defective mitochondrial complex I, idebenone leads to improved energy supply and a functional recovery of retinal ganglion cells during the acute stage of the disease, thereby preventing further vision loss and promoting recovery of vision. Thus, commencing treatment shortly after the onset of symptoms is likely to have the best therapeutic effect, a hypothesis that is supported by the available clinical data. PMID- 27186592 TI - PCSK9 inhibitors: monoclonal antibodies for the treatment of hypercholesterolemia. AB - In 2015 the U.S. Food and Drug Administration approved the first two proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, alirocumab (Praluent(r); Sanofi/ Regeneron) and evolocumab (Repatha(r); Amgen), for use in patients with heterozygous and homozygous familial hypercholesterolemia and for patients intolerant of statins or those with a major risk of cardiovascular disease (CVD) but unable to lower their LDL cholesterol (LDL-C) to optimal levels with statins and ezetimibe. Numerous randomized clinical trials have demonstrated that these inhibitors cause a fall in LDL-C levels of 50-60% as well as causing a decline in lipoprotein(a) and an increase in HDL cholesterol. They are effective in reducing levels of LDL-C to 1.8 mmol/L or less in almost all patients in the groups listed above except for those with homozygous familial hypercholesterolemia. In the latter case, many patients will still have LDL-C levels well above optimal levels despite the use of statins and a PCSK9 inhibitor. To date these inhibitors have not caused major adverse effects. However, the results of ongoing long-term randomized clinical trials are needed to determine whether they cause a significant reduction in CVD events including deaths from CVD. These studies will also demonstrate whether the PCSK9 inhibitors have any unexpected adverse effects and/or effects resulting from the loss of PCSK9 functions at other sites in the body, in particular regarding neurocognition. A further major concern is the high cost of PCSK9 inhibitors and their effect on healthcare costs and health insurance premiums. PMID- 27186593 TI - The impact of SPRINT on the future treatment of hypertension: a mini review. AB - Blood pressure (BP) control is associated with a significant decrease in the risk of coronary artery disease (CAD), stroke and chronic kidney disease (CKD), and U.S. treatment guidelines in 2003 and 2007 recommended a BP reduction to <140/90 mmHg for uncomplicated hypertension and to <130/80 mmHg for hypertension complicated by CAD, diabetes mellitus (DM) or CKD. In hopes of further decreasing the adverse effects of hypertension, more aggressive lowering of systolic blood pressure (SBP) was tested. However, this aggressive control of SBP did not materialize in additional cardiac benefits, and in fact resulted in worsening of cardiovascular and renal complications with the exception of stroke. These findings led national committees in 2014 and 2015 to draw up new guidelines recommending a relaxation of BP control based on recent clinical evidence, until publication of SPRINT. This National Institutes of Health (NIH)-sponsored study showed that aggressive SBP lowering to <120 mmHg was beneficial in further decreasing the risk of CVD, CVD mortality and strokes. The results of this study will most likely lead to the revision of current guidelines and to the recommendation of stricter BP control. However, the results of SPRINT are not final and still are in contrast with other recent studies. Until new guidelines become available, we should follow the current ones, or move closer to older guidelines depending on the clinical situation. A return to BP <140/90 mmHg for older subjects or uncomplicated hypertension and to <130/80 mmHg for hypertension complicated by CAD, DM and CKD may be appropriate. PMID- 27186594 TI - Duchenne muscular dystrophy drugs face tough path to approval. AB - Highly anticipated as new disease-modifying treatments for Duchenne muscular dystrophy (DMD), therapeutics by BioMarin Pharmaceutical (KyndrisaTM; drisapersen) and Sarepta Therapeutics (eteplirsen; AVI-4658) both recently received negative FDA reviews and are now facing battles for approval in the U.S. At present, BioMarin is committed to working with the FDA to forge a pathway to approval following the failure of its NDA, while Sarepta awaits the formal decision on its NDA, which is expected by late May 2016. Despite the critical nature of both reviews, analysts consider that there is still a narrow possibility of approval of both drugs. According to Consensus forecasts from Thomson Reuters Cortellis for Competitive Intelligence, Kyndrisa is forecast to achieve sales of USD 533.71 million in 2021. PMID- 27186595 TI - Pharma Pricing & Market Access Europe 2016--Health Network Communications' Tenth Annual Conference (February 23-25, 2016--London, UK). AB - Tighter national budgets and escalating drug prices continue to present challenges for pharmaceutical market access strategies and societal cost of care. As pharmaceutical companies and medical governmental advisory organizations enter tougher negotiations, hospital trusts and other dispensary firms face barriers to receiving the best medical treatment, and as a result patient access is limited. The 2016 HealthNetwork Communications' Pharma Pricing & Market Access Europe meeting brought together pharmaceutical, medical governmental advisory and stakeholders and market access/pricing consultants, to encourage discussions and negotiations into how to improve the drug pricing system and consequential market access strategies while achieving the respective reimbursement and affordability objectives. PMID- 27186596 TI - Evidence 2016--A Health Network Communications Conference (February 24-25, 2016- London, UK). AB - Defining, standardizing and interpreting are the keys to evidence use throughout healthcare and at each point in the care decision process. The generation of evidence at each step is also critical to define and constitute value from the information gathered, and not gathered, for each stakeholder in the care pathway. Health Network Communications' Evidence 2016 conference provided the opportunity for attendees to consider diverse evidence methodologies globally and their wide ranging use, from economic modeling initiatives, to framing value assessments in health technology assessments, to leveraging real-world data to support market access. PMID- 27186597 TI - Novel reduced graphene oxide-glycol chitosan nanohybrid for the assembly of an amperometric enzyme biosensor for phenols. AB - A novel water-soluble graphene derivative was prepared from graphene oxide via a two-step modification approach. Graphene oxide was first functionalised with reactive epoxy groups by covalent modification with (3 glycidyloxypropyl)trimethoxysilane and further cross-linked with glycol chitosan. This graphene derivative was characterized using different microscopy and physicochemical methods and employed as a coating material for a glassy carbon electrode. The nanostructured surface was used as a support for the covalent immobilization of the enzyme laccase through cross-linking with glutaraldehyde. The enzyme electrode was tested for the amperometric detection of different phenolic compounds, which displayed excellent analytical behaviour toward catechol with a linear range of response from 200 nM to 15 MUM, sensitivity of 93 mA M(-1) cm(-2), and low detection limit of 76 nM. The enzyme biosensor showed high stability when stored at 4 degrees C under dry conditions and was successfully employed to quantify the total phenolic compounds in commercial herbal tea samples. PMID- 27186598 TI - Freezing and melting line invariants of the Lennard-Jones system. AB - The invariance of several structural and dynamical properties of the Lennard Jones (LJ) system along the freezing and melting lines is interpreted in terms of isomorph theory. First the freezing/melting lines of the LJ system are shown to be approximated by isomorphs. Then we show that the invariants observed along the freezing and melting isomorphs are also observed on other isomorphs in the liquid and crystalline phases. The structure is probed by the radial distribution function and the structure factor and dynamics are probed by the mean-square displacement, the intermediate scattering function, and the shear viscosity. Studying these properties with reference to isomorph theory explains why the known single-phase melting criteria hold, e.g., the Hansen-Verlet and the Lindemann criteria, and why the Andrade equation for the viscosity at freezing applies, e.g., for most liquid metals. Our conclusion is that these empirical rules and invariants can all be understood from isomorph theory and that the invariants are not peculiar to the freezing and melting lines, but hold along all isomorphs. PMID- 27186600 TI - Chemical energy dissipation at surfaces under UHV and high pressure conditions studied using metal-insulator-metal and similar devices. AB - Metal heterostructures have been used in recent years to gain insights into the relevance of energy dissipation into electronic degrees of freedom in surface chemistry. Non-adiabaticity in the surface chemistry results in the creation of electron-hole pairs, the number and energetic distribution of which need to be studied in detail. Several types of devices, such as metal-insulator-metal, metal semiconductor and metal-semiconductor oxide-semiconductor, have been used. These devices operate by spatially separating the electrons from the holes, as an internal barrier allows only - or at least favours - transport from the top to the back electrode for one kind of carrier. An introduction into the matter, a survey of the literature and a critical discussion of the state of research is attempted. PMID- 27186599 TI - A DFT study of 2-aminopurine-containing dinucleotides: prediction of stacked conformations with B-DNA structure. AB - The fluorescence properties of dinucleotides incorporating 2-aminopurine (2AP) suggest that the simplest oligonucleotides adopt conformations similar to those found in duplex DNA. However, there is a lack of structural data for these systems. We report a density functional theory (DFT) study of the structures of 2AP-containing dinucleotides (deoxydinucleoside monophosphates), including full geometry optimisation of the sugar-phosphate backbone. Our DFT calculations employ the M06-2X functional for reliable treatment of dispersion interactions and include implicit aqueous solvation. Dinucleotides with 2AP in the 5'-position and each of the natural bases in the 3'-position are examined, together with the analogous 5'-adenine-containing systems. Computed structures are compared in detail with typical B-DNA base-step parameters, backbone torsional angles and sugar pucker, derived from crystallographic data. We find that 2AP-containing dinucleotides adopt structures that closely conform to B-DNA in all characteristic parameters. The structures of 2AP-containing dinucleotides closely resemble those of their adenine-containing counterparts, demonstrating the fidelity of 2AP as a mimic of the natural base. As a first step towards exploring the conformational heterogeneity of dinucleotides, we also characterise an imperfectly stacked conformation and one in which the bases are completely unstacked. PMID- 27186601 TI - New Fe(iii) and Co(ii) salen complexes with pendant distamycins: selective targeting of cancer cells by DNA damage and mitochondrial pathways. AB - Minor groove binding distamycin like moieties were conjugated with core salens and the corresponding Fe(iii) and Co(ii) complexes were synthesized. Herein, we have shown efficient DNA minor groove binding specificities along with excellent DNA cleavage capacities with metallosalen conjugates. The metal complexes showed toxicity toward various cancer cells over normal cells with high specificity. Interestingly, the Co(ii) complexes exhibited greater activity than the Fe(iii) complexes in accordance with the stronger affinity of the former in the biophysical studies. Active DNA damage, and prominent nuclear condensation along with the release of cytochrome-c from the mitochondria unanimously showed that the metal complexes followed apoptotic pathways to induce cell death. PMID- 27186602 TI - A novel multi-biofunctional protein from brown rice hydrolysed by endo/endo exoproteases. AB - Brown rice, which is a less allergenic food grain and contains essential amino acids, was hydrolysed by bromelain and PROTEASE FP51(r) to improve its functionalities and taste for food applications. The hydrolysate prepared by bromelain (eb-RPH) had high protein solubility, surface hydrophobicity, low molecular weight peptides, hydrophobic amino acids (leucine, valine and glycine) and flavor amino acids (glutamic acid and aspartic acid). The eb-RPH exhibited higher 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis 3 ethylbenzthiazoline-6-sulfonic (ABTS(+)) radical-scavenging activities of 76.62% and 52.96%, respectively, and possessed a better foaming capacity (221.76%) and emulsifying capacity (32.34%) than the hydrolysate prepared by PROTEASE FP51(r) (ep-RPH) did. The eb-RPH gave the desired taste, which is attributed to volatile flavor compounds (benzaldehyde, benzeneacetaldehyde and 2-acetyl-1-pyrroline) and non-volatile flavor compounds, such as monosodium glutamate, 5'-guanosine monophosphate and 5'-inosine monophosphate (0.07, 0.03 and 0.05 mg mL(-1), respectively). Brown rice peptides generated by bromelain were novel bioactive peptides with multifunctional properties. PMID- 27186603 TI - Application of isothermal titration calorimetry as a tool to study natural product interactions. AB - Covering: up to February 2015Over the past twenty-five years, isothermal titration calorimetry (ITC) has become a potent tool for the study a great variety of molecular interactions. This technique is able to provide a complete thermodynamic profile of an interaction process in a single experiment, with a series of advantages in comparison to other comparable techniques, such as less amount of sample or no need of chemical modification or labelling. It is thus not surprising that ITC has been applied to study the manifold types of interactions of natural products to get new insights into the molecular key factors implied in the complexation process of this type of compounds. This review provides an overview over the applications of ITC as a potent tool to investigate interactions of natural products with proteins, nucleic acids, oligosaccharides, and other types of receptors. The examples have been selected depending on the impact that this technique had during the investigation and revision of the interactions involved in the bioactivity of a compound, lead optimization or technical applications. PMID- 27186604 TI - Analysis of alcohol-induced DNA damage in Escherichia coli by visualizing single genomic DNA molecules. AB - Consumption of alcohol injures DNA, and such damage is considered to be a primary cause for the development of cancer and many other diseases essentially due to reactive oxygen species generated from alcohol. To sensitively detect alcohol induced DNA lesions in a biological system, we introduced a novel analytical platform for visualization of single genomic DNA molecules using E. coli. By fluorescently labelling the DNA lesions, our approach demonstrated, with the highest sensitivity, that we could count the number of DNA lesions induced by alcohol metabolism in a single bacterial cell. Moreover, our results showed a linear relationship between ethanol concentration and the number of DNA lesions: 0.88 lesions per 1% ethanol. Using this approach, we quantitatively analysed the DNA damage induced by exposure to alcoholic beverages such as beer (5% ethanol), rice wine (13%), soju (20%), and whisky (40%). PMID- 27186605 TI - Enzymatically catalytic signal tracing by a glucose oxidase and ferrocene dually functionalized nanoporous gold nanoprobe for ultrasensitive electrochemical measurement of a tumor biomarker. AB - A nanoporous gold nanosphere (pAu NS) was synthesized to load high-content glucose oxidase (GOx) and ferrocene (Fc) for the successful preparation of a new gold nanoprobe. After the specific recognition of the tumor biomarker of carcinoembryonic antigen (CEA) at a gold electrode based aptasensor, this GOx and Fc dually functionalized pAu NS nanoprobe was further used for sandwich immunoreaction and signal tracing. Based on the Fc-mediated GOx-catalytic reaction, the gold nanoprobes quantitatively captured onto the electrode surface produced a sensitive electrochemical signal corresponding to the protein recognition events, which led to the development of a new biosensing method for CEA measurement. Both the high loading of GOx and Fc on the pAu NS nanocarrier and the enzymatically catalytic reaction of the nanoprobe greatly amplify the electrochemical signal; meanwhile, the immobilization of the Fc mediator on this enzyme nanoprobe and the highly specific aptamer recognition drastically decrease the background current, resulting in the achievement of ultrahigh sensitivity of the method. Under optimum conditions, this method shows an excellent analytical performance including a wide linear relationship of five-order of magnitude and a low detection limit down to 0.45 pg mL(-1). Thus this pAu NS based gold nanoprobe and the proposed immunoassay method provide great potential for practical applications. PMID- 27186606 TI - A multi-responsive turn-on flurogenic probe to sense Zn(2+), Cd(2+) and Pb(2+): left-right-center emission signal swing. AB - A versatile new fluorogenic Schiff base probe (L) has been synthesized by the reaction of quinoline-2-carbohydrazide (which acts as the chelating site) and 4 dimethylamino cinnamaldehyde (which acts as the signaling unit). L can sense three of the most biologically and environmentally important metal ions, Zn(2+), Cd(2+) and Pb(2+), among various tested metal ions through selective TURN-ON fluorescence responses in physiological pH. Interestingly, L can not only sense Zn(2+), Cd(2+) and Pb(2+) fluorometrically in physiological conditions but can also distinguish one from another by exhibiting individual intrinsic left-right center TURN-ON emission signal swings. These selective fluorescence responses were explained by a chelation-enhanced fluorescence (CHEF) mechanism. Theoretical calculations were carried out to ascertain the preferred L-metal ion binding mode. PMID- 27186607 TI - Endonuclease IV cleaves apurinic/apyrimidinic sites in single-stranded DNA and its application for biosensing. AB - Endonuclease IV (Endo IV), as a DNA repairing enzyme, plays a crucial role in repairing damaged DNA comprising abasic sites to maintain genomic integrity. The cleaving capability of Endo IV to apurinic/apyrimidinic sites (AP) in single stranded DNA (ssDNA) was demonstrated. It was found that Endo IV has considerably high cleaving activity to AP sites in ssDNA compared with that in double-stranded DNA (dsDNA). The unique feature of Endo IV in cleaving AP sites in ssDNA was further applied to construct a novel dual signal amplified sensing system for highly sensitive enzyme and protein detection by a combination of exonuclease III (Exo III)-aided cyclic amplification reaction and a rolling circle replication (RCR) technique, which showed a good sensing performance with a detection limit of 0.008 U mL(-1) for Endo IV and 2.5 pM for streptavidin. In addition, the developed method had considerably high specificity for Endo IV and streptavidin over other potential interferences. The developed strategy indeed provides a novel platform for protein and enzyme assays and may find a broad spectrum of applications in bioanalysis, disease diagnosis, and drug development. PMID- 27186608 TI - In Memoriam: Professor Camille-Georges Wermuth. PMID- 27186609 TI - Synthesis of alpha-diazo-beta-keto esters, phosphonates and sulfones via acylbenzotriazole-mediated acylation of a diazomethyl anion. AB - We report a method for the synthesis of alpha-diazo-beta-keto esters, phosphonates and sulfones via acylation of corresponding diazomethyl anions with N-acylbenzotriazoles. The N-o-amino-acylbenzotriazoles exhibited an unprecedented transphosphorylation reaction leading to diazoacetyl phenylphosphoramidates. PMID- 27186610 TI - Response. PMID- 27186611 TI - Response. PMID- 27186612 TI - Response. PMID- 27186614 TI - [In memory of Tamata Oskarovna Faller (1920-2015)]. PMID- 27186613 TI - [Awake craniotomy]. AB - Awake craniotomy is a neurosurgical intervention aimed at identifying and preserving the eloquent functional brain areas during resection of tumors located near the cortical and subcortical language centers. This article provides a review of the modern literature devoted to the issue. The anatomical rationale and data of preoperative functional neuroimaging, intraoperative electrophysiological monitoring, and neuropsychological tests as well as the strategy of active surgical intervention are presented. Awake craniotomy is a rapidly developing technique aimed at both preserving speech and motor functions and improving our knowledge in the field of speech psychophysiology. PMID- 27186615 TI - EAPCI focus on the WEAPCI survey on radiation exposure and regulations in European catheterisation laboratories Julinda Mehilli, Chairwoman. PMID- 27186616 TI - Walking with patients is a privilege. PMID- 27186617 TI - The key is in the name. PMID- 27186618 TI - Chemotherapy of mantle cell lymphoma relapsed or refractory chronic lymphocytic leukaemia. PMID- 27186619 TI - COMMON STEM--(-)terol. PMID- 27186620 TI - vilanterol + fluticasone (RELVAR Ellipta). Asthma and COPD: yet another beta-2 agonist and corticosteroid combination. AB - As expected, the vilanterol + fluticasone combination increases the risk of pneumonia in patients with COPD. PMID- 27186621 TI - Olodaterol (Striverdi Respimat). COPD: just another beta-2 agonist. PMID- 27186622 TI - Venlafaxine: more dangerous than most "selective" serotonergic antidepressants. AB - Venlafaxine is a serotonergic and noradrenergic antidepressant. It shares the same serotonergic adverse effects as the "selective" serotonin reuptake inhibitor (SSRI) antidepressants while in addition provoking noradrenergic adverse effects, in particular cardiovascular disorders, yet offers no demonstrated advantages over SSRIs in terms of efficacy. Several cohort studies using data from a UK database have shown that venlafaxine overdoses are more frequently fatal than SSRI overdoses. Several meta-analyses of more than 70 published and unpublished randomised clinical trials, including about 7000 patients in total, have shown that treatment discontinuation due to adverse effects is more common with venlafaxine than with SSRI antidepressants. Venlafaxine can provoke dose dependent blood pressure elevation, sometimes requiring treatment discontinuation. Exposure to venlafaxine during the second and third trimesters of pregnancy increases the risk of pre-eclampsia and eclampsia. A cohort study in about 50 elderly patients and analysis of several hundred reported suicide attempts by venlafaxine overdose demonstrated a risk of QT interval prolongation, which can lead to torsades de pointes, an unusual and potentially fatal type of ventricular tachycardia. Large British and Danish cohort studies found no increased risk of sudden cardiac death with venlafaxine compared with other antidepressants. However, since only 3.5% and 7% of the patients were using venlafaxine, the statistical power of these studies was relatively low. In practice, the data available as of mid-2015 from clinical trials and epidemiological studies confirm the harms foreseeable from venlafaxine's pharmacological properties: a higher risk of cardiovascular adverse effects and of fatal overdoses than with most SSRI antidepressants. Since venlafaxine and SSRI antidepressants have similar and limited efficacy, venlafaxine is best avoided. An SSRI anti-depressant is a more reasonable option, with the exception of citalopram and escitalopram which also expose patients to more cardiovascular adverse effects. PMID- 27186623 TI - Citalopram, escitalopram: no more effective than other SSRIs, but more toxic. PMID- 27186624 TI - Allergic rhinitis during pregnancy. AB - During pregnancy, the first-choice drugs for allergic rhinitis are nasal or oral "non-sedating" antihistamines without antimuscarinic activity, in particular cetirizine, or loratadine after the first trimester. PMID- 27186625 TI - Drugs to avoid in pregnant women with allergies. PMID- 27186626 TI - Towards better patient care: drugs to avoid in 2016. AB - To help healthcare professionals and patients choose high-quality treatments that minimize the risk of adverse effects, in early 2016 we updated our list of drugs to avoid. Prescrire's assessments of the harm-benefit balance of new drugs and indications are based on a rigorous procedure that includes a systematic and reproducible literature search, identification of patient-relevant outcomes, prioritisation of the supporting data based on the strength of evidence, comparison with standard treatments, and an analysis of both known and potential adverse effects. This 2016 review of medications examined by Prescrire over a six year period, from 2010 to 2015, identified 74 drugs that are more harmful than beneficial in all the indications for which they have been authorised in France. In most cases, when drug therapy is really necessary, other drugs with a better harm-benefit balance are available. Even in serious situations, when no effective treatment exists, there is no justification for prescribing a drug with no proven efficacy that provokes severe adverse effects. It may be acceptable to test these drugs in clinical trials, but patients must be informed of the uncertainty over their harm-benefit balance, and the trial design must be relevant. Tailored supportive care is the best option when there are no available treatments capable of improving prognosis or quality of life, beyond the placebo effect. PMID- 27186627 TI - Notable changes in the 2016 update: citalopram, escitalopram, diclofenac added to the list of drugs to avoid. PMID- 27186628 TI - PCOS, breast hypoplasia and low milk supply: A case study. PMID- 27186629 TI - Metal-Free, Visible Light-Photocatalyzed Synthesis of Benzo[b]phosphole Oxides: Synthetic and Mechanistic Investigations. AB - Highly functionalized benzo[b]phosphole oxides were synthesized from reactions of arylphosphine oxides with alkynes under photocatalytic conditions by using eosin Y as the catalyst and N-ethoxy-2-methylpyridinium tetrafluoroborate as the oxidant. The reaction works under mild conditions and has a broad substrate scope. Mechanistic investigations have been undertaken and revealed the formation of a ground state electron donor-acceptor complex (EDA) between eosin (the photocatalyst) and the pyridinium salt (the oxidation agent). This complex, which has been fully characterized both in the solid state and in solution, turned out to exhibit a dual role, i.e., the oxidation of the photocatalyst and the formation of the initiating radicals, which undergoes an intramolecular reaction avoiding the classical diffusion between the two reactants. The involvement of ethoxy and phosphinoyl radicals in the photoreaction has unequivocally been evidenced by EPR spectroscopy. PMID- 27186630 TI - The effect of lifestyle-based education to women and their husbands on the anxiety and depression during pregnancy: a randomized controlled trial. AB - OBJECTIVE: The aim of this study was to determine the effect of lifestyle-based education to women and their husbands on anxiety and depression during pregnancy. METHOD: This controlled trial was conducted on 189 pregnant women. Participants were allocated into three groups through block randomization. In the first intervention group, both women and their husbands, and in the second one, only women received the lifestyle-based education. In the control group, women received only the routine care. Edinburgh depression and Spielberger anxiety questionnaires were completed at baseline and 8 weeks after it. RESULTS: Compared to the control group, significant reductions were observed in the scores of depression (adjusted difference: -4.7; 95% CI: -5.9 to -3.4), state anxiety ( 8.1; -11.3 to -4.9) and trait anxiety (-8.3; -11.9 to -5.0) in the first intervention group, and in the scores of depression (-2.9; -4.1 to -1.6), state anxiety (-4.3; -7.5 to -1.1) and trait anxiety (-5.5; 95% CI: -8.7 to -2.3) in the second intervention group. Comparing the two intervention groups, mean scores of depression and state anxiety were significantly lower in the first group. CONCLUSION: Results suggested the positive effect of lifestyle education to women and their husbands on depression and anxiety during pregnancy. PMID- 27186632 TI - Dimetallaborane analogues of the octaboranes of the type Cp2M2B6H10: structural variations with changes in the skeletal electron count. AB - The structures and energetics of the complete series of hydrogen-rich dimetallaboranes Cp2M2B6H10 and Cp*2M2B6H10 (Cp = eta(5)-C5H5; Cp* = eta(5) Me5C5; M = Pd, Pt; Rh, Ir; Ru, Os; Re; Mo, W; Ta), including the experimentally known Cp*2Rh2B6H10 and Cp*2W2B6H10 (Cp* = eta(5)-Me5C5), have been investigated by density functional theory. The lowest energy structures of the hyperelectronic Cp2M2B6H10 (M = Pd, Pt; Rh, Ir) systems have central M2B6 frameworks with a hexagonal open face similar to the B8 networks in arachno-B8H14 and nido-B8H12. The two lowest energy structures for Cp2Rh2B6H10 and Cp*2Rh2B6H10, lying within 1 kcal mol(-1) of energy, differ only in the locations of the bridging hydrogen atoms around the hexagonal hole consistent with the experimentally observed fluxionality of the hydrogen atoms in Cp*2Rh2B6H10. Most of the lowest energy Cp2M2B6H10 (M = Ru, Os) structures also have a central M2B6 framework similar to B8H12, typically with such additional features as an additional metal-metal bond or a formal metal-metal double bond. A common motif for the low-energy structures of the hypoelectronic Cp2M2B6H10 (M = Re; Mo, W; Ta) systems, including the experimentally known Cp*2W2B6H10, is a central M2B4 octahedron with its two M2B faces capped by the remaining boron atoms and with four M-B edges bridged by hydrogen atoms. Such structures can also be considered as oblatonido structures derived from the experimentally known 9-vertex oblatocloso Cp*2Re2B7H7 structure by removal of the unique degree 4 vertex atom. PMID- 27186631 TI - Effect of treatment with simvastatin on bone microarchitecture of the femoral head in an osteoporosis animal model. AB - The objective of this study was to evaluate the microarchitecture and trabecular bone strength at the distal region of the femur, and its biomechanical properties with simvastatin administration with two different doses in ovariectomized (OVX) rats. Ninety rats were divided into six groups to evaluate treatment with the simvastatin drug (n = 15): SH (Sham surgery), SH-5 (5 mg simvastatin), SH-20 (20 mg simvastatin), OVX, OVX-5, and OVX-20. Euthanasia was performed at three different times, five animals per period: 7, 14, and 28 days. The effectiveness of the treatments was evaluated by mechanical testing and histomorphometric analysis of the femurs. The results of analysis by the linear model of mixed effects showed 20 mg of simvastatin results in increased trabecular bone after 14 days (P = 0.039) of ingestion in ovariectomized animals. However, ingestion of 5 mg of simvastatin is able to sensitize the trabecular bone only at 28 days (P = 0.005) of ingestion. In the mechanical tests stiffness improves within 28 days (P = 0.003). Regarding maximum strength, no statistical differences were observed. According to these results, it can be concluded that for a decrease in oral intake, longer treatment times are required. Microsc. Res. Tech. 79:684-690, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27186633 TI - Post-synthetic modification of an amino-functionalized metal-organic framework for highly efficient enrichment of N-linked glycopeptides. AB - A maltose-functionalized metal-organic framework (MOF), MIL-101(Cr)-maltose, was developed via a simple two step post-synthetic modification of MIL-101(Cr)-NH2. With the use of this nanomaterial, 33 glycopeptides were detected from the digest of human immunoglobulin G, demonstrating its high efficiency in glycoproteomic analysis. More importantly, the generic functionalization route from amino derived MOFs opens a new perspective in material design in sample preparation. PMID- 27186634 TI - Fixed-dose combinations of drugs versus single-drug formulations for treating pulmonary tuberculosis. AB - BACKGROUND: People who are newly diagnosed with pulmonary tuberculosis (TB) typically receive a standard first-line treatment regimen that consists of two months of isoniazid, rifampicin, pyrazinamide, and ethambutol followed by four months of isoniazid and rifampicin. Fixed-dose combinations (FDCs) of these drugs are widely recommended. OBJECTIVES: To compare the efficacy, safety, and acceptability of anti-tuberculosis regimens given as fixed-dose combinations compared to single-drug formulations for treating people with newly diagnosed pulmonary tuberculosis. SEARCH METHODS: We searched the Cochrane Infectious Disease Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL, published in the Cochrane Library, Issue 11 2015); MEDLINE (1966 to 20 November 2015); EMBASE (1980 to 20 November 2015); LILACS (1982 to 20 November 2015); the metaRegister of Controlled Trials; and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), without language restrictions, up to 20 November 2015. SELECTION CRITERIA: Randomized controlled trials that compared the use of FDCs with single-drug formulations in adults (aged 15 years or more) newly diagnosed with pulmonary TB. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, and assessed the risk of bias and extracted data from the included trials. We used risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data with 95% confidence intervals (CIs). We attempted to assess the effect of treatment for time-to-event measures with hazard ratios and their 95% CIs. We used the Cochrane 'Risk of bias' assessment tool to determine the risk of bias in included trials. We used the fixed-effect model when there was little heterogeneity and the random-effects model with moderate heterogeneity. We used an I2 statistic value of 75% or greater to denote significant heterogeneity, in which case we did not perform a meta-analysis. We assessed the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: We included 13 randomized controlled trials (RCTs) in the review, which enrolled 5824 participants. Trials were published between 1987 and 2015 and included participants in treatment with newly diagnosed pulmonary TB in countries with high TB prevalence. Only two trials reported the HIV status of included participants.Overall there is little or no difference detected between FDCs and single-drug formulations for most outcomes reported. We did not detect a difference in treatment failure between FDCs compared with single-drug formulations (RR 1.28, 95% CI 0.82 to 2.00; 3606 participants, seven trials, moderate quality evidence). Relapse may be more frequent in people treated with FDCs compared to single-drug formulations, although the confidence interval (CI) includes no difference (RR 1.28, 95% CI 1.00 to 1.64; 3621 participants, 10 trials, low quality evidence). We did not detect any difference in death between fixed-dose and single-drug formulation groups (RR 0.96, 95% CI 0.67 to 1.39; 4800 participants, 11 trials, moderate quality evidence).When we compared FDCs with single-drug formulations we found little or no difference for sputum smear or culture conversion at the end of treatment (RR 0.99, 95% CI 0.96 to 1.02; 2319 participants, seven trials, high quality evidence), for serious adverse events (RR 1.45, 95% CI 0.90 to 2.33; 3388 participants, six trials, moderate quality evidence), and for adverse events that led to discontinuation of therapy (RR 0.96, 95% CI 0.56 to 1.66; 5530 participants, 13 trials, low quality evidence).We conducted a sensitivity analysis excluding studies at high risk of bias and this did not alter the review findings. AUTHORS' CONCLUSIONS: Fixed-dose combinations and single-drug formulations probably have similar effects for treating people with newly diagnosed pulmonary TB. PMID- 27186635 TI - Supplemental Breast Cancer Screening With Molecular Breast Imaging for Women With Dense Breast Tissue. AB - OBJECTIVE: Molecular breast imaging was implemented in routine clinical practice at a large community-based breast imaging center. The aim of this study was to retrospectively assess the clinical performance of molecular breast imaging as a supplementary screening tool for women with dense breast tissue. MATERIALS AND METHODS: Women with dense breasts and negative mammography results who subsequently underwent screening with 300 MBq (8 mCi) (99m)Tc-sestamibi molecular breast imaging were retrospectively analyzed. Outcome measures included cancer detection rate, recall rate, biopsy rate, and positive predictive values (PPVs). RESULTS: Molecular breast imaging screening of 1696 women in this study resulted in the detection of 13 mammographically occult malignancies, of which 11 were invasive, one was node positive, and one had unknown node positivity. The lesion size ranged from 0.6 to 2.4 cm, with a mean of 1.1 cm. The incremental cancer detection rate was 7.70/00 (95% CI, 4.5-13.10/00), the recall rate was 8.4% (95% CI, 7.2-9.8%), and the biopsy rate was 3.7% (95% CI, 2.9%-4.7%). The PPV for recall (PPV 1) was 9.1% (95% CI, 5.4-15.0%), and the PPV for biopsy (PPV 3) was 19.4% (95% CI, 11.4-30.9%). CONCLUSION: When incorporated into a community-based clinical practice environment, molecular breast imaging yielded a high incremental cancer detection rate of 7.70/00 at an acceptable radiation dose. These results show the utility of molecular breast imaging as a supplementary screening tool to mammography for women with dense breasts. PMID- 27186636 TI - Evaluation of Heavy Metal Removal from Wastewater in a Modified Packed Bed Biofilm Reactor. AB - For the effective application of a modified packed bed biofilm reactor (PBBR) in wastewater industrial practice, it is essential to distinguish the tolerance of the system for heavy metals removal. The industrial contamination of wastewater from various sources (e.g. Zn, Cu, Cd and Ni) was studied to assess the impacts on a PBBR. This biological system was examined by evaluating the tolerance of different strengths of composite heavy metals at the optimum hydraulic retention time (HRT) of 2 hours. The heavy metal content of the wastewater outlet stream was then compared to the source material. Different biomass concentrations in the reactor were assessed. The results show that the system can efficiently treat 20 (mg/l) concentrations of combined heavy metals at an optimum HRT condition (2 hours), while above this strength there should be a substantially negative impact on treatment efficiency. Average organic reduction, in terms of the chemical oxygen demand (COD) of the system, is reduced above the tolerance limits for heavy metals as mentioned above. The PBBR biological system, in the presence of high surface area carrier media and a high microbial population to the tune of 10 000 (mg/l), is capable of removing the industrial contamination in wastewater. PMID- 27186638 TI - Chemical Records in Snowpits from High Altitude Glaciers in the Tibetan Plateau and Its Surroundings. AB - Glaciochemistry can provide important information about climatic change and environmental conditions, as well as for testing regional and global atmospheric trace transport models. In this study, delta18O and selected chemical constituents records in snowpits collected from eight glaciers in the Tibetan Plateau and adjacent areas have been investigated. Drawing on the integrated data, our study summarized the seasonal and spatial characteristics of snow chemistry, and their potential sources. Distinct seasonal patterns of delta18O values in snowpits indicated more negative in the south TP controlled by Indian monsoon, and less negative in the north TP and Tien Shan. Overall increasing concentrations of microparticles and crustal ions from south to north indicated a strength of dust deposition on glaciers from semi-arid and arid regions. Principal component analysis and air mass trajectories suggested that chemical constituents were mainly attributable to crustal sources as demonstrated by the high concentrations of ions occurring during the non-monsoon seasons. Nevertheless, other sources, such as anthropogenic pollution, played an important role on chemical variations of glaciers near the human activity centers. This study concluded that air mass transport from different sources played important roles on the spatial distributions and seasonality of glaciochemistry. PMID- 27186637 TI - Characterization and Comparison of the CPK Gene Family in the Apple (Malus * domestica) and Other Rosaceae Species and Its Response to Alternaria alternata Infection. AB - As one of the Ca2+ sensors, calcium-dependent protein kinase (CPK) plays vital roles in immune and stress signaling, growth and development, and hormone responses, etc. Recently, the whole genome of apple (Malus * domestica), pear (Pyrus communis), peach (Prunus persica), plum (Prunus mume) and strawberry (Fragaria vesca) in Rosaceae family has been fully sequenced. However, little is known about the CPK gene family in these Rosaceae species. In this study, 123 CPK genes were identified from five Rosaceae species, including 37 apple CPKs, 37 pear CPKs, 17 peach CPKs, 16 strawberry CPKs, and 16 plum CPKs. Based on the phylogenetic tree topology and structural characteristics, we divided the CPK gene family into 4 distinct subfamilies: Group I, II, III, and IV. Whole-genome duplication (WGD) or segmental duplication played vital roles in the expansion of the CPK in these Rosaceae species. Most of segmental duplication pairs in peach and plum may have arisen from the gamma triplication (~140 million years ago [MYA]), while in apple genome, many duplicated genes may have been derived from a recent WGD (30~45 MYA). Purifying selection also played a critical role in the function evolution of CPK family genes. Expression of apple CPK genes in response to apple pathotype of Alternaria alternata was verified by analysis of quantitative real-time RT-PCR (qPCR). Expression data demonstrated that CPK genes in apple might have evolved independently in different biological contexts. The analysis of evolution history and expression profile laid a foundation for further examining the function and complexity of the CPK gene family in Rosaceae. PMID- 27186640 TI - Correction: Characterisation of Mesothelioma-Initiating Cells and Their Susceptibility to Anti-Cancer Agents. AB - [This corrects the article DOI: 10.1371/journal.pone.0119549.]. PMID- 27186639 TI - In-Depth Analysis of HA and NS1 Genes in A(H1N1)pdm09 Infected Patients. AB - In March/April 2009, a new pandemic influenza A virus (A(H1N1)pdm09) emerged and spread rapidly via human-to-human transmission, giving rise to the first pandemic of the 21th century. Influenza virus may be present in the infected host as a mixture of variants, referred to as quasi-species, on which natural and immune driven selection operates. Since hemagglutinin (HA) and non-structural 1 (NS1) proteins are relevant in respect of adaptive and innate immune responses, the present study was aimed at establishing the intra-host genetic heterogeneity of HA and NS1 genes, applying ultra-deep pyrosequencing (UDPS) to nasopharyngeal swabs (NPS) from patients with confirmed influenza A(H1N1)pdm09 infection. The intra-patient nucleotide diversity of HA was significantly higher than that of NS1 (median (IQR): 37.9 (32.8-42.3) X 10(-4) vs 30.6 (27.4-33.6) X 10(-4) substitutions/site, p = 0.024); no significant correlation for nucleotide diversity of NS1 and HA was observed (r = 0.319, p = 0.29). Furthermore, a strong inverse correlation between nucleotide diversity of NS1 and viral load was observed (r = - 0.74, p = 0.004). For both HA and NS1, the variants appeared scattered along the genes, thus indicating no privileged mutation site. Known polymorphisms, S203T (HA) and I123V (NS1), were observed as dominant variants (>98%) in almost all patients; three HA and two NS1 further variants were observed at frequency >40%; a number of additional variants were detected at frequency <6% (minority variants), of which three HA and four NS1 variants were novel. In few patients multiple variants were observed at HA residues 203 and 222. According to the FLUSURVER tool, some of these variants may affect immune recognition and host range; however, these inferences are based on H5N1, and their extension to A(H1N1)pdm09 requires caution. More studies are necessary to address the significance of the composite nature of influenza virus quasi-species within infected patients. PMID- 27186641 TI - Elevated Serum ADA Activity as a Marker for Diagnosis and Prognosis of Visceral Leishmaniasis and Post Kala-Azar Dermal Leishmaniasis in Indian Patients. AB - Serum adenosine deaminase (ADA) activity increases in diseases where cellular immunity is involved. Since cell-mediated immune responses play a paramount role in the pathogenesis and healing of the visceral leishmaniasis, therefore, the present study was undertaken to evaluate the serum ADA activity in different pathological conditions. Adenosine deaminase was determined in sera of active visceral leishmaniasis (VL) patients (n = 39), active postkala-azar dermal leishmaniasis (PKDL) cases (n = 34) at the point of diagnosis and after treatment stages along with healthy controls (n = 30), endemic healthy subjects (n = 34) and endemic asymptomatic subjects (n = 34).Our in-vitro result revealed that monocytes secrete significant ADA level in response to Leishmania donovani (L.donovani) stimulation. The serum ADA activity in active VL and PKDL subjects were found to be significantly higher than that of respective treated cases and healthy controls. We also observed a marginal number (17.6%) of endemic asymptomatic subjects showed elevated serum ADA activity. Further, the ADA activity in PKDL was found to be decreased gradually during the different phases of treatment. Interestingly, 2 out of 32 treated VL cases found to have high serum ADA activity during follow up period were relapsed within few days. These results suggest the possibility of ADA as a marker of clinical pathogenesis and can be used as a surrogate marker in the diagnosis and prognosis of VL and PKDL. PMID- 27186642 TI - Modulation in Persistent Organic Pollutant Concentration and Profile by Prey Availability and Reproductive Status in Southern Resident Killer Whale Scat Samples. AB - Persistent organic pollutants (POPs), specifically PCBs, PBDEs, and DDTs, in the marine environment are well documented, however accumulation and mobilization patterns at the top of the food-web are poorly understood. This study broadens the understanding of POPs in the endangered Southern Resident killer whale population by addressing modulation by prey availability and reproductive status, along with endocrine disrupting effects. A total of 140 killer whale scat samples collected from 54 unique whales across a 4 year sampling period (2010-2013) were analyzed for concentrations of POPs. Toxicant measures were linked to pod, age, and birth order in genotyped individuals, prey abundance using open-source test fishery data, and pregnancy status based on hormone indices from the same sample. Toxicant concentrations were highest and had the greatest potential for toxicity when prey abundance was the lowest. In addition, these toxicants were likely from endogenous lipid stores. Bioaccumulation of POPs increased with age, with the exception of presumed nulliparous females. The exceptional pattern may be explained by females experiencing unobserved neonatal loss. Transfer of POPs through mobilization of endogenous lipid stores during lactation was highest for first-borns with diminished transfer to subsequent calves. Contrary to expectation, POP concentrations did not demonstrate an associated disruption of thyroid hormone, although this association may have been masked by impacts of prey abundance on thyroid hormone concentrations. The noninvasive method for measuring POP concentrations in killer whales through scat employed in this study may improve toxicant monitoring in the marine environment and promote conservation efforts. PMID- 27186644 TI - Effect of tumor necrosis factor-alpha inhibitors on ambulatory 24-h blood pressure. AB - Tumor necrosis factor alpha (TNF-alpha) inhibitors are increasingly being used in inflammatory rheumatic diseases (IRD). The risk of cardiovascular disease is elevated in patients with IRD and TNF-alpha inhibitors reduce this risk. We assessed whether the beneficial effect of TNF-alpha inhibitors on cardiovascular risk is mediated by blood pressure reduction. We measured blood pressure levels with 24-h ambulatory blood pressure measurements device in patients with IRD before and 3 months after treatment with TNF-alpha inhibitors. The study population consisted of 15 subjects (6 men; mean age 45.9 +/- 14.1 years). Most patients had either rheumatoid arthritis or psoriatic arthritis and adalimumab was the most common TNF-alpha inhibitor used. Mean 24-h systolic and diastolic blood pressure levels remained the same after treatment (121 +/- 12/66 +/- 7 before and 123 +/- 11/67 +/- 10 mm Hg after; p = 0.88 and 0.66, respectively). The study demonstrates that TNF-alpha inhibitors have no effect on blood pressure levels. PMID- 27186643 TI - Impaired Ethanol-Induced Sensitization and Decreased Cannabinoid Receptor-1 in a Model of Posttraumatic Stress Disorder. AB - BACKGROUND AND PURPOSE: Impaired striatal neuroplasticity may underlie increased alcoholism documented in those with posttraumatic stress disorder (PTSD). Cannabinoid receptor-1 (CB1) is sensitive to the effects of ethanol (EtOH) and traumatic stress, and is a critical regulator of striatal plasticity. To investigate CB1 involvement in the PTSD-alcohol interaction, this study measured the effects of traumatic stress using a model of PTSD, mouse single-prolonged stress (mSPS), on EtOH-induced locomotor sensitization and striatal CB1 levels. METHODS: Mice were exposed to mSPS, which includes: 2-h restraint, 10-min group forced swim, 15-min exposure to rat bedding odor, and diethyl ether exposure until unconsciousness or control conditions. Seven days following mSPS exposure, the locomotor sensitizing effects of EtOH were assessed. CB1, post-synaptic density-95 (PSD95), and dopamine-2 receptor (D2) protein levels were then quantified in the dorsal striatum using standard immunoblotting techniques. RESULTS: Mice exposed to mSPS-EtOH demonstrated impaired EtOH-induced locomotor sensitization compared to Control-EtOH mice, which was accompanied by reduced striatal CB1 levels. EtOH increased striatal PSD95 in control and mSPS-exposed mice. Additionally, mSPS-Saline exposure increased striatal PSD95 and decreased D2 protein expression, with mSPS-EtOH exposure alleviating these changes. CONCLUSIONS: These data indicate that the mSPS model of PTSD blunts the behavioral sensitizing effects of EtOH, a response that suggests impaired striatal neuroplasticity. Additionally, this study demonstrates that mice exposed to mSPS and repeated EtOH exposure decreases CB1 in the striatum, providing a mechanism of interest for understanding the effects of EtOH following severe, multimodal stress exposure. PMID- 27186647 TI - Silicon Oxycarbide/Carbon Nanohybrids with Tiny Silicon Oxycarbide Particles Embedded in Free Carbon Matrix Based on Photoactive Dental Methacrylates. AB - A new facile scalable method has been developed to synthesize silicon oxycarbide (SiOC)/carbon nanohybrids using difunctional dental methacrylate monomers as solvent and carbon source and the silane coupling agent as the precursor for SiOC. The content (from 100% to 40% by mass) and structure (ratio of disordered carbon over ordered carbon) of the free carbon matrix have been systematically tuned by varying the mass ratio of methacryloxypropyltrimethoxysilane (MPTMS) over the total mass of the resin monomers from 0.0 to 6.0. Compared to the bare carbon anode, the introduction of MPTMS significantly improves the electrochemical performance as a lithium-ion battery anode. The initial and cycled discharge/charge capacities of the SiOC/C nanohybrid anodes reach maximum with the MPTMS ratio of 0.50, which displays very good rate performance as well. Detailed structures and electrochemical performance as lithium-ion battery anodes have been systematically investigated. The structure-property correlation and corresponding mechanism have been discussed. PMID- 27186646 TI - Disc height loss and restoration via injectable hydrogel influences adjacent segment mechanics in-vitro. AB - BACKGROUND: Height loss can have a profound influence on the local mechanical environment of the disc. While disc height loss is incorporated into scales of degeneration, its direct influence on spine kinematics is unclear. Further, there is a need for minimally invasive techniques to restore disc height; injectable hydrogels are a potential solution. Tandem investigation of disc height loss and subsequent restoration will enhance understanding of spine dysfunction and aberrant movement. METHODS: Twenty porcine spine specimens with two functional segments were tested in repeated flexion and extension. Relative angular displacement of each segment was measured with full specimen disc height, disc height loss in one of the segments (superior or inferior), and disc height restoration via hydrogel injection. FINDINGS: Disc height loss decreased the range of motion at the affected segment and increased the range of motion at the adjacent segment. Relative angular displacement decreased at the affected segment by 13.8% (SD=5.3%) and 4.5% (SD=2.1%) for specimens with height loss in the superior and inferior discs respectively. Hydrogel injection was able to restore segmental kinematics to the pre-injury state, with 12.7% (SD=5.5%) and 6.4% (SD=4.2%) of motion regained at the affected segment for superior and inferior disc height loss specimens respectively. INTERPRETATION: Acute disc height loss reduces motion at an affected segment, while increasing motion at an adjacent segment in-vitro; relative motion appears to be governed by local stiffness. Injectable hydrogels show promise in their ability to restore kinematics to segments with disc height loss. PMID- 27186648 TI - A new coumarin from the roots of Micromelum minutum. AB - A new coumarin, minutuminolate (1), together with eleven known coumarins (2-12), was isolated from the roots of Micromelum minutum. The structures of these compounds were established on the basis of their 1D and 2D NMR spectroscopic data. Compounds 2, 5, 10, 11 and 12 showed cytotoxicity against KB cell line. In addition, compounds 2, 3, 4, 7, 11 and 12 also showed weak cytotoxicity against NCI-H187 cell line. PMID- 27186645 TI - Prioritizing Surgical Care on National Health Agendas: A Qualitative Case Study of Papua New Guinea, Uganda, and Sierra Leone. AB - BACKGROUND: Little is known about the social and political factors that influence priority setting for different health services in low- and middle-income countries (LMICs), yet these factors are integral to understanding how national health agendas are established. We investigated factors that facilitate or prevent surgical care from being prioritized in LMICs. METHODS AND FINDINGS: We undertook country case studies in Papua New Guinea, Uganda, and Sierra Leone, using a qualitative process-tracing method. We conducted 74 semi-structured interviews with stakeholders involved in health agenda setting and surgical care in these countries. Interviews were triangulated with published academic literature, country reports, national health plans, and policies. Data were analyzed using a conceptual framework based on four components (actor power, ideas, political contexts, issue characteristics) to assess national factors influencing priority for surgery. Political priority for surgical care in the three countries varies. Priority was highest in Papua New Guinea, where surgical care is firmly embedded within national health plans and receives significant domestic and international resources, and much lower in Uganda and Sierra Leone. Factors influencing whether surgical care was prioritized were the degree of sustained and effective domestic advocacy by the local surgical community, the national political and economic environment in which health policy setting occurs, and the influence of international actors, particularly donors, on national agenda setting. The results from Papua New Guinea show that a strong surgical community can generate priority from the ground up, even where other factors are unfavorable. CONCLUSIONS: National health agenda setting is a complex social and political process. To embed surgical care within national health policy, sustained advocacy efforts, effective framing of the problem and solutions, and country-specific data are required. Political, technical, and financial support from regional and international partners is also important. PMID- 27186649 TI - Association between presence of pneumonia and pressure ulcer formation following traumatic spinal cord injury. AB - OBJECTIVE: To determine if the presence of pneumonia and pressure ulcers are associated in individuals with an acute spinal cord injury during acute care and rehabilitation hospitalizations. DESIGN: Retrospective, secondary analyses of data obtained from the Spinal Cord Injury Model Systems enrolled from 1993 until 2006 Setting: Acute care hospitalization and inpatient rehabilitation facilities Participants: A cohort of individuals hospitalized in acute care (n = 3,098) and inpatient rehabilitation (n = 1,768) was included in the analysis. Frequencies of pressure ulcer formation and episodes of pneumonia were noted in both settings. INTERVENTIONS: Not applicable. OUTCOME MEASURES: Pressure ulcer formation and diagnosis of pneumonia Results: The development of pressure ulcers, including stage I, was 20.3% acute care and 21.1% during in inpatient rehabilitation. Multivariate logistic regression analyses revealed a significant association of pneumonia with occurrence of pressure ulcers (P <= 0.001, OR = 2.3 and 2.2 respectively), the American Spinal Injury Association Impairment Scale grades (P < 0.001), and utilization of mechanical ventilation (P < 0.01) in both settings. CONCLUSION: A higher presence of pressure ulcers was found in individuals with pneumonia, after adjusting for injury severity, age, sex, and utilization of mechanical ventilation. Impaired inflammatory response and decreased mobility in individuals with pneumonia may predispose these individuals to develop pressure ulcers. Surveillance and preventive measures for pressure ulcers should be rigorous in individuals with SCI and pneumonia. PMID- 27186650 TI - Social anxiety following traumatic brain injury: an exploration of associated factors. AB - Social anxiety (SA) following traumatic brain injury (TBI) has the potential to affect an individual's general psychological well-being and social functioning, however little research has explored factors associated with its development. The present study used hierarchical multiple regression to investigate the demographic, clinical and psychological factors associated with SA following TBI. A sample of 85 people who experienced TBI were recruited through social media websites and brain injury services across the North-West of England. The overall combined biopsychosocial model was significant, explaining 52-54.3% of the variance in SA (across five imputations of missing data). The addition of psychological variables (self-esteem, locus of control, self-efficacy) made a significant contribution to the overall model, accounting for an additional 12.2 13% of variance in SA above that explained by demographic and clinical variables. Perceived stigma was the only significant independent predictor of SA (B = .274, p = .005). The findings suggest that psychological variables are important in the development of SA following TBI and must be considered alongside clinical factors. Furthermore, the significant role of stigma highlights the need for intervention at both an individualised and societal level. PMID- 27186651 TI - Erratum: Chromatin-associated degradation is defined by UBXN-3/FAF1 to safeguard DNA replication fork progression. PMID- 27186652 TI - Self-Assembled Epitaxial Au-Oxide Vertically Aligned Nanocomposites for Nanoscale Metamaterials. AB - Metamaterials made of nanoscale inclusions or artificial unit cells exhibit exotic optical properties that do not exist in natural materials. Promising applications, such as super-resolution imaging, cloaking, hyperbolic propagation, and ultrafast phase velocities have been demonstrated based on mostly micrometer scale metamaterials and few nanoscale metamaterials. To date, most metamaterials are created using costly and tedious fabrication techniques with limited paths toward reliable large-scale fabrication. In this work, we demonstrate the one step direct growth of self-assembled epitaxial metal-oxide nanocomposites as a drastically different approach to fabricating large-area nanostructured metamaterials. Using pulsed laser deposition, we fabricated nanocomposite films with vertically aligned gold (Au) nanopillars (~20 nm in diameter) embedded in various oxide matrices with high epitaxial quality. Strong, broad absorption features in the measured absorbance spectrum are clear signatures of plasmon resonances of Au nanopillars. By tuning their densities on selected substrates, anisotropic optical properties are demonstrated via angular dependent and polarization resolved reflectivity measurements and reproduced by full-wave simulations and effective medium theory. Our model predicts exotic properties, such as zero permittivity responses and topological transitions. Our studies suggest that these self-assembled metal-oxide nanostructures provide an exciting new material platform to control and enhance optical response at nanometer scales. PMID- 27186653 TI - Highly Enantioselective Iridium-Catalyzed Hydrogenation of Cyclic Enamides. AB - The MaxPHOX-Ir catalyst system provided the highest selectivity ever reported for the reduction of cyclic enamides derived from alpha- and beta-tetralones. This result indicates that iridium catalysts are also proficient in reducing alkenes bearing metal-coordinating groups. In the present system, selectivity was pressure-dependent: In most cases, a decrease in the H2 pressure to 3 bar resulted in an increase in enantioselectivity. Moreover, the process can be carried out in environmentally friendly solvents, such as methanol and ethyl acetate, with no loss of selectivity. PMID- 27186655 TI - Influence of dietary protein on serum metabolites and antioxidant status: A study in Chrysolophus amherstiae. AB - This experiment was conducted to study the effect of feeding graded levels of dietary crude protein (CP) on serum biochemical profile of Lady Amherst's pheasants (LAP). Eighteen male LAP were randomly distributed into three groups of six each in an experiment based on completely randomized design. The CP content of the diets was 13.4%, 16.5%, and 19.1%, in groups I, II, and III, respectively. Serum concentrations of uric acid was lowest (P < 0.05) in group I. Relationship between serum concentration of uric acid and nitrogen intake was linear (R(2) = 0.39, P < 0.01). Concentrations of other serum metabolites and enzymes were similar among the groups. Serum concentration of triiodothyronine (T3 ) was highest (P < 0.05) in group I, followed by groups II and III. Total antioxidant capacity (TAC) of serum was lower (P < 0.007), whereas serum concentration of malondialdehyde (MDA) was higher (P < 0.001) in group I as compared to groups II and III. Regression of serum concentration of TAC (R(2) = 0.74, P < 0.01) and MDA (R(2) = 0.39, P < 0.05) was polynomial. Heterophil to lymphocyte ratio was higher (P < 0.007) in group I as compared to groups II and III. Relationship between H/L ratio and nitrogen intake was polynomial (R(2) = 0.69, P < 0.05). Cell mediated immune response measured as foot web index was similar among the groups. Based upon the results, it was concluded that a diet containing 16.5% crude protein would be optimum for improving antioxidant defense and the ability of Lady Amherst's pheasant to combat stress. Zoo Biol. 35:346-354, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27186654 TI - Development of a new therapeutic technique to direct stem cells to the infarcted heart using targeted microbubbles: StemBells. AB - Successful stem cell therapy after acute myocardial infarction (AMI) is hindered by lack of engraftment of sufficient stem cells at the site of injury. We designed a novel technique to overcome this problem by assembling stem cell microbubble complexes, named 'StemBells'. StemBells were assembled through binding of dual-targeted microbubbles (~3MUm) to adipose-derived stem cells (ASCs) via a CD90 antibody. StemBells were targeted to the infarct area via an ICAM-1 antibody on the microbubbles. StemBells were characterized microscopically and by flow cytometry. The effect of ultrasound on directing StemBells towards the vessel wall was demonstrated in an in vitro flow model. In a rat AMI reperfusion model, StemBells or ASCs were injected one week post-infarction. A pilot study demonstrated feasibility of intravenous StemBell injection, resulting in localization in ICAM-1-positive infarct area three hours post-injection. In a functional study five weeks after injection of StemBells cardiac function was significantly improved compared with controls, as monitored by 2D echocardiography. This functional improvement neither coincided with a reduction in infarct size as determined by histochemical analysis, nor with a change in anti- and pro-inflammatory macrophages. In conclusion, the StemBell technique is a novel and feasible method, able to improve cardiac function post-AMI in rats. PMID- 27186656 TI - Targeting the Breast Cancer Kinome. AB - Protein kinases are highly tractable targets for the treatment of many cancers including breast cancer, due to their essential role in tumor cell proliferation and survival. Sequencing of the breast cancer genome and transcriptome has defined breast cancer as a heterogeneous disease that is classified into five molecular subtypes: luminal A, luminal B, HER2-enriched, basal-like, and claudin low. Each subtype displays a unique expression profile of protein kinases that can be targeted by small molecule kinase inhibitors or biologics. An understanding of genomic changes, including mutations or copy number variations, for specific protein kinases and dependencies on kinases across breast cancer subtypes is allowing for a more rational design of targeted breast cancer therapies. While specific kinase inhibitors have had success in the clinic, including the CDK4/6 inhibitor palbociclib in combination with aromatase inhibitors in luminal breast cancer, patients often become resistant to treatment. An understanding of the mechanisms allowing cells to bypass targeted kinase inhibition has led to the development of combination therapies that are more durable in pre-clinical studies. However, the heterogeneity of resistance mechanisms and rapid adaptability of the kinome through feedback regulation greatly inhibit the long-term efficacy of combination kinase inhibitor therapies. It is becoming apparent that epigenetic inhibitors, such as HDAC and BET bromodomain inhibitors can block the transcriptional adaptability of tumor cells to kinase inhibitors and prevent the onset of resistance. Such novel combination therapies are currently showing promise in preclinical studies to markedly increase the durability of kinase inhibitors in breast cancer. J. Cell. Physiol. 232: 53-60, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27186657 TI - Multiepitope Templates Imprinted Particles for the Simultaneous Capture of Various Target Proteins. AB - To achieve the simultaneous capture of various target proteins, the multiepitope templates imprinted particles were developed by phase inversion-based poly(ether sulfone) (PES) self-assembly. Herein, with the top three high-abundance proteins in the human plasma, serum albumin, immunoglobulin G, and transferrin, as the target proteins, their N-terminal peptides were synthesized as the epitope templates. After the preorganization of three epitopes and PES in dimethylacetamide, the multiepitope templates imprinted particles were formed in water through self-assembly, by which the simultaneous recognition of three target proteins in human plasma was achieved with high selectivity. Furthermore, the binding kinetics study proved that the adsorption mechanism in this imprinting system toward three epitope templates was the same as that on the single-epitope imprinting polymer. These results demonstrate that our proposed multiepitope templates imprinting strategy might open a new era of artificial antibodies to achieve the recognition of various targets simultaneously. PMID- 27186658 TI - Ecological Importance of Small-Diameter Trees to the Structure, Diversity and Biomass of a Tropical Evergreen Forest at Rabi, Gabon. AB - Tropical forests have long been recognized for their biodiversity and ecosystem services. Despite their importance, tropical forests, and particularly those of central Africa, remain understudied. Until recently, most forest inventories in Central Africa have focused on trees >=10 cm in diameter, even though several studies have shown that small-diameter tree population may be important to demographic rates and nutrient cycling. To determine the ecological importance of small-diameter trees in central African forests, we used data from a 25-ha permanent plot that we established in the rainforest of Gabon to study the diversity and dynamics of these forests. Within the plot, we censused 175,830 trees >=1 cm dbh from 54 families, 192 genera, and 345 species. Average tree density was 7,026 trees/ha, basal area 31.64 m2/ha, and above-ground biomass 369.40 Mg/ha. Fabaceae, Ebenaceae and Euphorbiaceae were the most important families by basal area, density and above-ground biomass. Small-diameter trees (1 cm >= dbh <10 cm) comprised 93.7% of the total tree population, 16.5% of basal area, and 4.8% of the above-ground biomass. They also had diversity 18% higher at family level, 34% higher at genus level, and 42% higher at species level than trees >=10 cm dbh. Although the relative contribution of small-diameter trees to biomass was comparable to other forests globally, their contribution to forest density, and diversity was disproportionately higher. The high levels of diversity within small-diameter classes may give these forests high levels of structural resilience to anthropogenic/natural disturbance and a changing climate. PMID- 27186659 TI - Effect of catechins on fattening performance, meat quality, some antioxidant and blood parameters and fattening costs in Japanese quail (Coturnix coturnix japonica). AB - The aim of this study was to investigate the effect of dietary supplementation of green tea (Camellia sinensis) catechins in quail (Coturnix coturnix japonica). Quail were fed with a basal diet, and the treatment groups were fed on the basal diet with 1.25 or 2.50 g/kg catechin supplementation for 30 d. Fattening performance and meat quality of the quail were estimated. Serum total antioxidant status (TAS), plasma and liver malondialdehyde (MDA) and some serum biochemical parameters were measured. The results showed that catechin supplementation did not affect live weight, feed intake, feed conversion ratio, carcass weight, carcass dressing or the nutrient composition of breast and thigh meats. The water holding capacity (WHC) of breast meat was increased in the 2.50 g/kg catechin treatment. Catechin supplementation increased the serum TAS, but decreased plasma MDA and liver MDA concentration as well as serum glucose and total cholesterol levels. Serum triglyceride and total protein levels were not affected by catechin supplementation. In conclusion, catechins have effective antioxidant hypoglycaemic and hypocholesterolaemic properties, as well as having the potential to increase meat quality in fattening quail. On the other hand, catechin supplementation did not have any negative effect on the fattening performance, meat nutrient composition and fattening costs in fattening quail. PMID- 27186660 TI - Effect of Assembly pH on Polyelectrolyte Multilayer Surface Properties and BMP-2 Release. AB - The effect of solution pH during layer-by-layer assembly of polyelectrolyte multilayer (PEM) coatings on properties relevant to orthopedic implant success was investigated. Bone morphogenetic protein 2 (BMP-2), a potent osteoconductive growth factor, was adsorbed onto the surface of anodized titanium, and PEM coatings prepared from solutions of poly-l-histidine and poly(methacrylic acid) were built on top of the BMP-2. High levels of BMP-2 released over several months were achieved. Approximately 2 MUg/cm(2) of BMP-2 were initially adsorbed on the anodized titanium and a pH-dependent release behavior was observed, with more stable coatings assembled at pH = 6-7. Three different diffusion regimes could be determined from the release profiles: an initial burst release, a sustained release regime, and a depletion regime. BMP-2 was shown to maintain bioactivity after release from a PEM and the presence of a PEM was shown to preserve BMP-2 structure. No visible change was observed in surface roughness as the assembly pH was varied, whereas the surface energy decreased for samples prepared at more basic pH. These results indicate that the initial BMP-2 layer affects PEM surface structure, but not the functional groups exposed on the surface. PMID- 27186661 TI - Self-Diffusiophoresis of Janus Catalytic Micromotors in Confined Geometries. AB - The self-diffusiophoresis of Janus catalytic micromotors (JCMs) in confined environment is studied using direct numerical simulations. The simulations revealed that, on average, the translocation of a JCM through a short pore is moderately slowed down by the confinement. This slowdown is far weaker compared to the transport of particles through similar pores driven by forces induced by external means or passive diffusiophoresis. Pairing of two JCMs facilitates the translocation of the one JCM entering the pore first but slows down the second JCM. Depending on its initial orientation, a JCM near the entrance of a pore can exhibit different rotational motion, which determines whether it can enter the pore. Once a JCM enters a narrow pore, it can execute a self-alignment process after which it becomes fully aligned with the pore axis and moves to the center line of the pore. Analysis of these results showed that, in addition to hydrodynamic effect, the translation and rotation of JCM is also affected by the "chemical effects", i.e., the modification of the chemical species concentration around a JCM by confining walls and neighboring JCMs. These chemical effects are unique to the self-diffusiophoresis of JCMs and should be considered in design and operations of JCMs in confined environment. PMID- 27186662 TI - Direct Diastereo- and Enantioselective Vinylogous Michael Additions of Linear Enones. AB - A direct vinylogous Michael addition using linear vinylogous Michael donors has been developed. Notably, even gamma-substituted Michael donors cleanly afforded gamma-alkylated products in high yield and ee by this method. Moreover, control experiments revealed that, for these and related linear vinylogous Michael donors, the size of the Michael acceptor strongly influences whether alpha- or gamma-alkylation occurs, not simply blocking effects of cocatalysts as suggested previously. PMID- 27186663 TI - Controlling the Ratio between Native-Like, Non-Native-Like, and Aggregated beta Lactoglobulin after Heat Treatment. AB - The amount of heat-denatured whey protein is typically determined by pH 4.6 precipitation. Using this method, a significant amount of nondenatured protein was reported even after long heating times. Apparently, a fraction of the unfolded protein refolds into the "native" state rather than form aggregates. This fact is known and has been explained using kinetic models. How the conditions affect the refolding and aggregation is, however, not fully understood. Therefore, this study investigates the unfolding, refolding, and aggregation process of beta-lactoglobulin using circular dichroism and size exclusion chromatography to characterize different folding variants and to quantify their content. The proteins remaining in solution at pH 4.6 were confirmed to be native-like. The nonaggregated fraction contains proteins with a native-like and two types of non-native-like conformations. The nonaggregated fraction increased with decreasing temperature (60-90 degrees C) and concentration (1-50 g/L) and increasing electrostatic repulsion (pH 7-8; 0-50 mM). The native-like fraction in the nonaggregated fraction was independent of pH, ionic strength, and concentration but increased with decreasing temperature. PMID- 27186665 TI - Improved pharmacokinetics and antihyperlipidemic efficacy of rosuvastatin-loaded nanostructured lipid carriers. AB - In the present study, rosuvastatin calcium-loaded nanostructured lipid carriers were developed and optimized for improved efficacy. The ROS-Ca-loaded NLC was prepared using melt emulsification ultrasonication technique and optimized by Box Behnken statistical design. The optimized NLC composed of glyceryl monostearate (solid lipid) and capmul MCM EP (liquid lipid) as lipid phase (3% w/v), poloxamer 188 (1%) and tween 80 (1%) as surfactant. The mean particle size, polydispersity index (PDI), zeta potential (zeta) and entrapment efficiency (%) of optimized NLC formulation was observed to be 150.3 +/- 4.67 nm, 0.175 +/- 0.022, -32.9 +/- 1.36 mV and 84.95 +/- 5.63%, respectively. NLC formulation showed better in vitro release in simulated intestinal fluid (pH 6.8) than API suspension. Confocal laser scanning showed deeper permeation of formulation across rat intestine compared to rhodamine B dye solution. Pharmacokinetic study on female albino Wistar rats showed 5.4-fold increase in relative bioavailability with NLC compared to API suspension. Optimized NLC formulation also showed significant (p < 0.01) lipid lowering effect in hyperlipidemic rats. Therefore, NLC represents a great potential for improved efficacy of ROS-Ca after oral administration. PMID- 27186666 TI - Cavity Femtochemistry: Manipulating Nonadiabatic Dynamics at Avoided Crossings. AB - Molecular potential energy surfaces can be actively manipulated by light. This is usually done by strong classical laser light but was recently demonstrated for the quantum field in an optical cavity. The photonic vacuum state of a localized cavity mode can be strongly mixed with the molecular degrees of freedom to create hybrid field-matter states known as polaritons. We simulate the avoided crossing of sodium iodide in a cavity by incorporating the quantized cavity field into the nuclear wave packet dynamics calculation. The quantized field is represented on a numerical grid in quadrature space, thus avoiding the limitations set by the rotating wave approximation (RWA) when the field is expanded in Fock space. This approach allows the investigation of cavity couplings in the vicinity of naturally occurring avoided crossings and conical intersections, which is too expensive in the fock space expansion when the RWA does not apply. Numerical results show how the branching ratio between the covalent and ionic dissociation channels can be strongly manipulated by the optical cavity. PMID- 27186664 TI - Accelerated Discovery of Thermoelectric Materials: Combinatorial Facility and High-Throughput Measurement of Thermoelectric Power Factor. AB - A series of processes have been developed to facilitate the rapid discovery of new promising thermoelectric alloys. A novel combinatorial facility where elements are wire-fed and laser-melted was designed and constructed. Different sample compositions can be achieved by feeding different element wires at specific rates. The composition of all the samples prepared was tested by energy dispersive X-ray spectroscopy (EDS). Then, their thermoelectric properties (power factor) at room temperature were screened in a specially designed new high throughput setup. After the screening, the thermoelectric properties can be mapped with the possibility of identifying compositional trends. As a proof-of concept, a promising thermoelectric ternary system, Al-Fe-Ti, has been identified, demonstrating the capability of this accelerated approach. PMID- 27186667 TI - Decimetre-scale multicellular eukaryotes from the 1.56-billion-year-old Gaoyuzhuang Formation in North China. AB - Fossils of macroscopic eukaryotes are rarely older than the Ediacaran Period (635 541 million years (Myr)), and their interpretation remains controversial. Here, we report the discovery of macroscopic fossils from the 1,560-Myr-old Gaoyuzhuang Formation, Yanshan area, North China, that exhibit both large size and regular morphology. Preserved as carbonaceous compressions, the Gaoyuzhuang fossils have statistically regular linear to lanceolate shapes up to 30 cm long and nearly 8 cm wide, suggesting that the Gaoyuzhuang fossils record benthic multicellular eukaryotes of unprecedentedly large size. Syngenetic fragments showing closely packed ~10 MUm cells arranged in a thick sheet further reinforce the interpretation. Comparisons with living thalloid organisms suggest that these organisms were photosynthetic, although their phylogenetic placement within the Eukarya remains uncertain. The new fossils provide the strongest evidence yet that multicellular eukaryotes with decimetric dimensions and a regular developmental program populated the marine biosphere at least a billion years before the Cambrian Explosion. PMID- 27186679 TI - Regulation of Rap GTPases in mammalian neurons. AB - Small GTPases are central regulators of many cellular processes. The highly conserved Rap GTPases perform essential functions in the mammalian nervous system during development and in mature neurons. During neocortical development, Rap1 is required to regulate cadherin- and integrin-mediated adhesion. In the adult nervous system Rap1 and Rap2 regulate the maturation and plasticity of dendritic spine and synapses. Although genetic studies have revealed important roles of Rap GTPases in neurons, their regulation by guanine nucleotide exchange factors (GEFs) that activate them and GTPase activating proteins (GAPs) that inactivate them by stimulating their intrinsic GTPase activity is just beginning to be explored in vivo. Here we review how GEFs and GAPs regulate Rap GTPases in the nervous system with a focus on their in vivo function. PMID- 27186676 TI - Development of Purine-Based Hydroxamic Acid Derivatives: Potent Histone Deacetylase Inhibitors with Marked in Vitro and in Vivo Antitumor Activities. AB - In the present study, a series of novel histone deacetylase (HDAC) inhibitors using the morpholinopurine as the capping group were designed and synthesized. Several compounds demonstrated significant HDAC inhibitory activities and antiproliferative effects against diverse human tumor cell lines. Among them, compound 10o was identified as a potent class I and class IIb HDAC inhibitor with good pharmaceutical profile and druglike properties. Western blot analysis further confirmed that 10o more effectively increased acetylated histone H3 than panobinostat (LBH-589) and vorinostat (SAHA) at the same concentration in vitro. In in vivo efficacy evaluations of HCT116, MV4-11, Ramos, and MM1S xenograft models, 10o showed higher efficacy than SAHA or LBH-589 without causing significant loss of body weight and toxicity. All the results indicated that 10o could be a suitable candidate for treatment of both solid and hematological cancer. PMID- 27186678 TI - Biological characteristics of renal cancer cells after CTP-mediated cancer suppressor gene NPRL2 protein treatment. AB - Nitrogen permease regulator like-2 (NPRL2) has been proved to be a useful suppressor gene in treating many cancers containing renal cancer based on experiments. Transgenic technology which transfect exogenous NPRL2 gene into cancer cell was used in these experiments. However, this technology has defects, such as gene mutation and loss. Cytoplasmic transduction peptide (CTP) can be used to avoid these defects because it can directly mediate proteins to penetrate cell membrane and specifically locate in cytoplasm. In this article, CTP was used to directly mediate NPRL2 protein into the renal cancer cell line 786-O, then cell proliferation was detected by the CCK-8 method, cell cycle and apoptosis were detected by flow cytometry, cell invasion and migration ability were detected by the Transwell assay. Bcl-xl, Cyt-c and caspase-3 were detected by real-time fluorescent quantitative PCR and Western blot for the analysis of the related mechanism. The result showed that CTP successfully mediated NPRL2 protein into renal cancer cells and the growth of cells was significantly inhibited. The mechanism may be NPRL2 down-regulating the expression of Bcl-xl which can up regulate Cyt-c and further activate caspase-3, and then a cascade reaction is caused for cell apoptosis on the classic mitochondrial apoptosis pathway. PMID- 27186677 TI - MicroRNA-544 down-regulates both Bcl6 and Stat3 to inhibit tumor growth of human triple negative breast cancer. AB - Triple negative breast cancer lacking estrogen receptor (ER), progesterone receptor and Her2 account for account for the majority of the breast cancer deaths, due to the lack of specific gene targeted therapy. Our current study aimed to investigate the role of miR-544 in triple negative breast cancer. Endogenous levels of miR-544 were significantly lower in breast cancer cell lines than in human breast non-tumorigenic and mammary epithelial cell lines. We found that miR-544 directly targeted the 3'-untranslated region (UTR) on both Bcl6 and Stat3 mRNAs, and overexpression of miR-544 in triple negative breast cancer cells significantly down-regulated expressions of Bcl6 and Stat3, which in turn severely inhibited cancer cell proliferation, migration and invasion in vitro. Employing a mouse xenograft model to examine the in vivo function of miR-544, we found that expression of miR-544 significantly repressed the growth of xenograft tumors. Our current study reported miR-544 as a tumor-suppressor microRNA particularly in triple negative breast cancer. Our data supported the role of miR 544 as a potential biomarker in developing gene targeted therapies in the clinical treatment of triple negative breast cancer. PMID- 27186680 TI - Benchmark Quantum Mechanical Calculations of Vibrationally Resolved Cross Sections and Rate Constants on ab Initio Potential Energy Surfaces for the F + HD Reaction: Comparisons with Experiments. AB - Quantum scattering calculations within the time-independent approach in an extended interval of energies were performed for the title reaction on four ab initio potential energy surfaces. The calculated integral cross sections, vibrational branching ratios, and rate constants are compared with scattering experiments as well as with chemical kinetics rate data available for this system for both the HF and DF channels. The calculations on the CSZ (J. Chem. Phys. 2015, 142, 024303) and LWAL (J. Chem. Phys. 2007, 127, 174302) surfaces are in close agreement between them and reproduce satisfactorily the experimental measurements. The agreement with the experiments is improved with respect to calculations on the earlier SW (J. Chem. Phys. 1996, 104, 6515) and FXZ (J. Chem. Phys. 2008, 129, 011103) surfaces. The results presented here witness the remarkable progress made by quantum chemistry calculations in describing the interatomic interactions governing the dynamics and kinetics of this reaction. They also suggest that comparison with translationally and rotationally averaged experimental observables is not sufficient to assess the relative accuracy of highly accurate potential energy surfaces. The dynamics and kinetics calculations show that temperatures lower than 50 K or molecular beam energy spread below 1 meV must be reached to discriminate the accuracy of the LWAL and the CSZ surfaces. PMID- 27186682 TI - Primary Effusion Lymphoma (PEL)-Like Lymphoma in a Child With Congenital Immunodeficiency. AB - Primary effusion lymphoma (PEL) is a rare lymphoma that occurs more frequently in immunocompromised adults and has a poor survival. We report a 9-year-old female with combined immunodeficiency with an Epstein-Barr virus positive/human herpes virus 8 negative PEL-like lymphoma. The treatment with systemic chemotherapy for non-Hodgkin lymphoma, zidovudine, and interferon-alpha failed to control disease progression. This is the first reported pediatric case of PEL-like lymphoma. Increased diagnostic awareness and more effective treatment strategies are needed for this rare lymphoma. PMID- 27186684 TI - A Qualitative Comparison of Susceptibility and Behavior in Recreational and Occupational Risk Environments: Implications for Promoting Health and Safety. AB - Although internal factors that influence risk are frequently studied to understand human behavior, external factors, including social, cultural, and institutional factors, should be better utilized to inform ways to efficiently target, tailor, and promote safety messaging to at-risk populations. Semi structured interviews obtained data from 37 motorcyclists and 18 mineworkers about their risk perceptions and behaviors within their respective dynamic environments. A comparative thematic analysis revealed information about external factors that influence risk perceptions and behaviors. Results support the importance of qualitative approaches for assessing and targeting individuals' risk perceptions and behaviors. In addition, segmenting at-risk subgroups within target populations and tailoring messages for these at-risk groups is critical for safety behavior modification. Practitioners should utilize strategic, culture centric risk communication that takes into account external factors when determining when, who, and what to communicate via health promotion activities to more accurately disseminate valid, empathetic, and engaging communication with a higher level of fidelity. PMID- 27186685 TI - Experimental study of liquid carbon. AB - Direct measurements of the functional dependencies of the electric resistivity and the molar volume on enthalpy and pressure have been performed for graphite and liquid carbon. It has been found that for graphite at the pressures P ? 1 GPa the isochoric temperature coefficient of resistance is positive, while for liquid carbon it is negative over the entire pressure range investigated where P = 0.5-3.5 GPa. These observations probably indicate that graphite is a metal whereas liquid carbon is not a metal, so that the melting of graphite under such pressures coincides with a metal-to-nonmetal transition. PMID- 27186683 TI - Mortality Reduction and Long-Term Compliance with Surviving Sepsis Campaign: A Nationwide Multicenter Study. AB - PURPOSE: To determine the long-term degree of compliance with the Surviving Sepsis Campaign (SSC) bundles and related outcomes after an educational program in septic patients admitted to a network of intensive care units (ICU). METHODS: Prospective, observational, multicenter study in several ICUs during a 5-month period for evaluating the degree of compliance with the SSC bundles of resuscitation in the first 6 h (B6H) and management in the following 24 h (B24H). We compared the findings with those from a historical cohort at the same ICUs after an educational program (EDUSEPSIS) 5 years earlier. RESULTS: The study cohort comprised 231 episodes of severe sepsis and the historical cohort included 217. In the current cohort, we found a better compliance with B6H compared with the historical cohort (27.7% vs. 9.7%, P < 0.001), and lower compliance with B24H (4.3% vs. 12.9%, P < 0.001). ICU and in-hospital mortalities were reduced from 37.3% to 27.1% (P = 0.02) and from 45.3% to 36.7% (P = 0.06), respectively. This reduction occurred linearly with the number of B6H items completed (P for trend <0.001). All B6H measures were individually associated with lower ICU mortality. Measurement of plasma lactate, blood cultures, and administration of broad spectrum antibiotics were associated with lower in-hospital mortality. No benefit was observed regarding B24H. CONCLUSIONS: Our study confirmed that an educational campaign aimed at early recognition and management of patients with severe sepsis improves compliance with management recommendations and hospital survival in the long term. PMID- 27186686 TI - Prediction of powdered activated carbon doses for 2-MIB removal in drinking water treatment using a simplified HSDM approach. AB - The addition of powdered activated carbon (PAC) is an effective measure to cope with seasonal taste and odor (T&O) problems caused by 2-methylisoborneol (2-MIB) and trans-1, 10-dimethyl-trans-9-decalol (geosmin) in drinking water. Some T&O problems are episodic in nature, and generally require rapid responses. This paper proposed a simplified approach for the application of the homogenous surface diffusion model (HSDM) to predict the appropriate PAC doses for the removal of 2-MIB. Equilibrium and kinetic experiments were performed for 2-MIB adsorption onto five PACs in three source waters. The simplified HSDM approach was compared with the experimental data, by assigning the Freundlich 1/n value in the range of 0.1-1.0 and obtaining the Freundlich equilibrium parameter K value through a 6-hr adsorption kinetic test. The model describes the kinetic adsorption data very well for all of the tested PACs in different source waters. The results were validated using the data obtained from one full scale water treatment plant, and the differences between the predicted and observed results were within 10% range. This simplified HSDM approach may be applied for the rapid determination of PAC doses for water treatment plants when faced with 2-MIB episodes in source waters. PMID- 27186687 TI - Development of new transition metal oxide catalysts for the destruction of PCDD/Fs. AB - Various transition metal oxide and vanadium-containing multi-metallic oxide catalysts were developed for the destruction of PCDD/Fs (polychlorinated dibenzo p-dioxins and furans). A stable PCDD/Fs generating system was installed to support the catalytic destruction tests in this study. Nano-titania supported vanadium catalyst (VOx/TiO2) showed the highest activity, followed by CeOx, MnOx, WOx and finally MoOx. Multi-metallic oxide catalysts, prepared by doping WOx, MoOx, MnOx and CeOx into VOx/TiO2 catalysts, showed different activities on the decomposition of PCDD/Fs. The highest destruction efficiency of 92.5% was observed from the destruction test over VOxCeOx/TiO2 catalyst. However, the addition of WOx and MoOx even played a negative role in multi-metallic VOx/TiO2 catalysts. Characterizations of transition metal oxides and multi-metallic VOx/TiO2 catalysts were also investigated with XRD and TPR. After the catalysts were used, the conversion from high valent metals to low valence states was observed by XPS. PMID- 27186688 TI - Association of cadmium in urine and blood with age in a general population with low environmental exposure. AB - A recent study reported a nonlinear and nonmonotonic relationship between urinary cadmium (U-Cd) and age and questioned the long-held view that U-Cd is a reliable biomarker of Cd body burden at low exposure levels. In order to reassess the significance of U-Cd as biomarker of Cd body burden, we studied the lifetime trend of U-Cd as functions of diuresis in a cross-sectional study. Cadmium was measured with an inductively coupled plasma mass spectrometer (ICP-MS) for the general population taking part in the Metals and Health Survey in Jiangsu (MHSJ), China, with ages ranging from 2.8 to 86.8 years (n = 1235). Variations in U-Cd and B-Cd with age were modeled using natural cubic splines. Factors associated with U-Cd were analyzed with Pearson correlation and linear regression models. As results, nonsmoking men had peak U-Cd at approximately 60 years, after which it decreased. In nonsmoking women, U-Cd increased from 2.8 years to 50 years, then leveled off. In both genders, B-Cd increased from birth to approximately 30 years and then leveled off. U-Cd, expressed in per liter, was consistently associated with B-Cd and U-creatinine, regardless of smoking status. U-Cd and B-Cd were not significantly higher in former smokers than never smokers. Our study suggests that individual U-Cd level are correlated with B-Cd and U-creatinine, and needed to be appropriately adjusted for B-Cd and U-creatinine, when it is used for a biomarker of kidney burden of Cd. PMID- 27186689 TI - Nontarget approach for environmental monitoring by GC * GC-HRTOFMS in the Tokyo Bay basin. AB - In this study, we developed an approach for sequential nontarget and target screening for the rapid and efficient analysis of multiple samples as an environmental monitoring using a comprehensive two-dimensional gas chromatograph coupled to a high resolution time-of-flight mass spectrometer (GC * GC-HRTOFMS). A key feature of the approach was the construction of an accurate mass spectral database learned from the sample via nontarget screening. To enhance the detection power in the nontarget screening, a global spectral deconvolution procedure based on non-negative matrix factorization was applied. The approach was applied to the monitoring of rivers in the Tokyo Bay basin. The majority of the compounds detected by the nontarget screening were alkyl chain-based compounds (55%). In the quantitative target screening based on the output from the nontarget screening, particularly high levels of organophosphorus flame retardants (median concentrations of 31, 116 and 141 ng l(-1) for TDCPP, TCIPP and TBEP, respectively) were observed among the target compounds. Flame retardants used for household furniture and building materials were detected in river basins where buildings and arterial traffic were dominated. The developed GC * GC-HRTOFMS approach was efficient and effective for environmental monitoring and provided valuable new information on various aspects of monitoring in the context of environmental management. PMID- 27186690 TI - Phytoremediation of lead using Ipomoea aquatica Forsk. in hydroponic solution. AB - Ipomoea aquatica Forsk., an aquatic macrophyte, was assessed for its ability to accumulate lead (Pb) by exposing it to graded concentrations of this metal. Accumulation of Pb was the highest in root followed by that in stem and leaf with translocation factor (TF) values of less than unity. On the other hand, all bioconcentration factor (BCF) values in root, stem and leaf were greater than unity. Furthermore, exposure to Pb concentrations over about 20 mg L(-1) induced colour changes in the basal portion of stem which had significantly higher Pb accumulation than that in the unaffected apical part. This resulted in sequestration of excess metal in affected stem tissue, which could take up Pb by the process of caulofiltration or shoot filtration, and served as a secondary reservoir of Pb in addition to the root. The apical parts contained less lead and could regrow roots from nodes and survive when kept in Pb-free medium. The ability of the plant to store Pb in its root and lower part of stem coupled with its ability to propagate by fragmentation through production of adventitious roots and lateral branches from nodes raises the possibility of utilizing Ipomoea aquatica for Pb phytoremediation from liquid effluent. PMID- 27186691 TI - Ocular findings in a patient with Cockayne syndrome with two mutations in the ERCC6 gene. AB - BACKGROUND: Cockayne syndrome is a rare, autosomal recessive, multisystem disorder that causes a senile appearance. Ophthalmic abnormalities are frequently present. Here, we report a wide range of ocular findings in a child with Cockayne syndrome. MATERIALS AND METHODS: The systemic and ocular findings were reviewed. A mutation analysis was performed in the patient and her parents. RESULTS: The patient underwent a complete ocular examination. Both eyes had low visual acuity, corneal epithelial degeneration, punctate opacities of the lens, and retina disorders. The systemic findings included growth deficiency and a senile appearance. Gene analysis showed mutations in exons 4 and 18 of the ERCC6 gene. CONCLUSION: Multiple ocular abnormalities were observed in a patient with Cockayne syndrome. A detailed ophthalmic evaluation of children with Cockayne syndrome is advised. PMID- 27186693 TI - Systems-level analysis of genome wide association study results for a pilot juvenile idiopathic arthritis family study. AB - Genome wide association studies (GWAS) determine susceptibility profiles for complex diseases. In this study, GWAS was performed in 26 patients with oligo and rheumatoid factor negative polyarticular juvenile idiopathic artritis (JIA) and their healthy parents by Affymetrix 250K SNP arrays. Biological function and pathway enrichment analysis was done. This is the first GWAS reported for JIA families from the eastern Mediterranean population. Enrichment of FcgammaR mediated phagocytosis pathway and response to various stimuli were the leading discoveries, along with the presentation of the strong interaction of JIA associated genes with HLA cluster in the co-expression network. The co-expression network also presented the direct interaction of a gene in FcgammaRmediated phagocytosis pathway, namely GAB2, with BLK, CDH13, IL4R and MICA. The systems biology approach helped us to investigate the interactions between the identified genes and biological pathways and molecular functions, expanding our understanding of JIA pathogenesis at molecular level. PMID- 27186696 TI - Serum vitamin B12, folic acid, and homocysteine levels in children with febrile seizure. AB - The aim of this study is to investigate the associations between febrile seizure and serum levels of vitamin B12, folic acid, and homocysteine. One hundred and four children who presented with febrile seizure and 75 controls who presented with febrile illness unaccompanied by seizure were enrolled into the study. Mean levels of vitamin B12, folic acid and homocysteine were compared between two groups. Mean vitamin B12 level in the febrile seizure group was significantly lower than the control group. The febrile seizure patients with 3 or more had significantly lower serum folic acid than the subgroups with two or one episode only. Serum concentrations of folic acid were significantly lower in the febrile seizure subgroup with body temperature 37.5-39.0C at time of convulsion. Low serum vitamin B12 may reduce a child's threshold for seizure and may be a risk factor for febrile seizure. Low serum folic acid level may be predisposed to recurrent febrile seizure. PMID- 27186697 TI - Incidence and follow-up outcomes of developmental hip dysplasia of newborns in the Western Mediterranean Region. AB - The aim of our study was to determine the incidence of developmental hip dysplasia (DHD) in the Western Mediterranean Region of Turkey and evaluate follow up results of physiologically immature hips classified as type 2 according to Graf classification. Ultrasononographic examinations of the hips were performed using Graf's technique on 1162 infants (2324 hips) referred to our clinic for hip ultrasounds between March 2013 and March 2014. DHD was detected in 1.36% of 1162 infants. Among infants who were brought into repetitive follow-ups, 191 out of type 2a hip displasias of 201 infants were improved to type 1 and 10 type 2a hip dysplasias worsened. Sonographically worsened tip 2a group consisted of 4 type 2b, 6 type 2c DHDs. Hip ultrasound performed during neonatal period and infancy in the detection of developmental hip dysplasias and follow-up of hip dysplasias diagnosed as type 2a convey importance because of sonographically detected potential deterioration. PMID- 27186698 TI - Prognostic factors and treatment results of pediatric Hodgkin's lymphoma: A single center experience. AB - The aim of this study was to assess the demographic, clinic data, prognostic factors and treatment/follow-up results of children who were diagnosed with Hodgkin lymphoma and followed in our center of Pediatric Oncology, Kocaeli University Medical Faculty, Kocaeli, Turkey, for 10 years. This retrospective study evaluated 41 patients with Hodgkin lymphoma who were younger than 18 years old. All patients were treated with risked adapted ABVD (Adriamycin, Bleomycin, Vincristine, Dacarbazine) chemotherapy and also received involved field radiotherapy. Thirty-two patients (78%) were males and 9 (22%) were females, with a mean age of 10.7+/-4.0 years. The histopathological diagnosis was mixed cellular type in 51.2% of the patients. B symptoms (unexplained fever, unexplained weight loss, drenching night sweats) were present in 53.7% of the patients and 36.6% of the patients were at advanced stage at the time of the diagnosis. The 3-year overall and event-free survival rates were 88% and 5-year overall and event-free survival rates were 88%, 78%. Age, stage, treatment risk groups, presence of B symptoms and hematological parameters had no significant effect on overall and event-free survival in univariate analysis while bulky disease was the only significant factor on overall survival. Our treatment policy was succesful regarding the similar survival rates in the treatment risk groups, however novel treatment strategies adopting the early response with the reduction of adverse effects are planned in the near future. PMID- 27186699 TI - Predictive factor for first wheezing episode. AB - The aim of study was to evaluate various risk in patients who were hospitalized with moderate to severe virus-induced wheezing. Infants hospitalized with virus induced wheezing were enrolled in the study. Respiratory viruses were detected in nasopharyngeal swab and total IgE levels and skin prick tests were performed in all patients. The mean age of the patients was 11.2+/-9 months. The most common detected viral agents were Respiratory Syncytial Virus, (33.6%), Influenza virus (16.3.%). Children with positive family history of atopy had their first virus induced wheezing at an earlier age (9.0 +/-7.8 months) than the others (14.2+/ 10.8 months), (p=0.007). Atopy and viral etiology did not significantly influence clinical severity of the disease. Although children with positive parental history of atopy experience first virus-induced wheezing at an earlier age, personal atopy was not found as a risk factor for predicting the severity of the first virus-induced wheezy episode. PMID- 27186700 TI - Is compliance with gluten-free diet sufficient? Diet composition of celiac patients. AB - This study was planned to investigate the amount and content of foods consumed by child patients with celiac disease on a long-term gluten-free diet. Children aged 3-18 years who were diagnosed with celiac disease according to ESPGHAN criteria and were compliant to the gluten-free diet for at least one year were included. Age and gender matched healthy children were included as the control group. Food consumption records including the amount and content of the foods consumed for a total of three days were obtained. Once the records had been completed on the food consumption form, quantity analysis was again performed by the same dietician. Energy and other nutritional elements taken in through foodstuffs consumed by the patient and control groups were calculated using the Nutrition Data System for Research Package; these results were shown as mean +/- standard deviation (x +/-SD) and the values compared. The study consisted of 28 patients with a mean age of 10.3 +/- 4.6 and 25 healthy controls with a mean age of 9.5 +/ 3.4. Average age at diagnosis in the patient group was 6.7 +/- 4.3 and mean duration of gluten-free diet was 4.0 +/- 3.3 years. Children with celiac disease on a gluten-free diet had significantly lower daily energy intake levels compared to the healthy controls (p<0.05). The proportional fat consumption was significantly higher in the patient group compared to the controls (p<0.05). Moreover, proportional carbohydrate and protein, vitamin E and vitamin B1, and microelements such as magnesium, phosphorus and zinc consumptions were significantly lower in celiac group with respect to v-control group. Solely determining compliance to the gluten free diet might be inadequate in the follow up of children with celiac disease, adequacy of the nutritional content in terms of macro and micronutrients of celiac disease patients is also important. PMID- 27186701 TI - Clinical features and long-term outcomes of idiopathic urethrorrhagia. AB - The aim of this study was to describe the clinical features and long-term outcome of the patients who were treated at our institution for idiopathic urethrorrhagia. The data of 10 male patients, who underwent cystoscopy between October 2010 and March 2013 due to urethrorrhagia, were evaluated retrospectively. Ten male patients aged between 8 and 16 years at first submission. Four patients (40%) had low voiding frequency (2-3 per day). Three of the four patients had abnormal uroflowmetry/EMG findings. Cystoscopy was done in all patients which revealed bulbar urethral inflammation and hemorrhage in all. Symptoms were not resolved on three of the patients who were under observation, having symptoms on average for 29.6+/-10.5 months. Complete resolution developed in the other seven patients. Six of the patients' symptoms were resolved soon after cystoscopy. In the patients' with or without normal uroflowmetry/EMG findings urethrorrhagia resolution rates were 86% and 33%, respectively. In the evaluation of urethrorrhagia; detailed history taking, basic laboratory investigation and cystoscopy are enough. The typical patients may be treated expectantly. In our opinion, it seems that dysfunctional voiding and infrequent voiding might cause delayed remission and/or recurrence of urethrorrhagia. Even though, it does not effect the treatment, in the persistent cases, confirmation of diagnosis by cystoscopy helps to lessen the anxiety of the family and might decrease the use of many unnecessary diagnostic tools in the long term follow ups. PMID- 27186702 TI - Pyloric atresia-junctional epidermolysis bullosa syndrome showing novel c.4505 4508insACTC mutations in integrin b4 gene (ITGB4). AB - Epidermolysis bullosa (EB) is a group of inherited blistering skin diseases that vary widely in their pathogenesis and severity. It has been divided into distinct subtypes depending on the level of tissue separation in the dermal- epidermal basement membrane zone. There are four main categories of EB: simplex, junctional, dystrophic and Kindler syndrome. Junctional epidermolysis bullosa with pyloric atresia (JEB-PA) is a rare autosomal recessive form and characterized by severe mucocutaneous blisters and gastric outlet obstruction. Most of the mutations in JEP-PA are associated with the alpha6beta4 integrin genes (ITGA6, ITGB4,). Herein, we present a female newborn with lethal JEB-PA caused by a novel beta4 integrin mutation. PMID- 27186704 TI - Pyridoxine-dependent epilepsy in two Turkish patients in Turkey and review of the literature. AB - Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive enzyme defect in the vitamin B6 metabolism characterized by intractable seizures which are usually resistant to all antiepileptic drugs but respond to pharmacological doses of pyridoxine. We present the clinical and molecular genetic findings of two patients with c.1597_1597delG mutations in ALDH7A1 gene. There are different clinical phenotypes in PDE: patients with complete seizure control with pyridoxine and normal development (group 1), patients with complete seizure control with pyridoxine and development delay (group 2), and patients with persistent seizures despite pyridoxine treatment and with development delay (group 3). Our two patients have persistant seizure despite pyridoxine treatment and with development delay. Pyridoxine-dependent epilepsy can be identified in any neonate with signs of encephalopathy and refractory seizures, with no evidence of hypoxic-ischemic damage or other underlying metabolic disturbance. Neurodevelopmental outcomes of patients with PDE is multifactorial; early diagnosis and treatment of these patients is vital. PMID- 27186703 TI - Two Turkish siblings with MEGDEL syndrome due to novel SERAC1 gene mutation. AB - Association of 3-methylglutaconic aciduria with impaired oxidative phosphorylation, deafness, encephalopathy, leigh-like lesions on brain imaging, progressive spasticity and dystonia defined as a distinct entity under the name of MEGDEL syndrome. It is an autosomal recessive disorder due to mutation in the serine active site-containing protein 1 (SERAC1). SERAC1 is localized at the interface between the mitochondria and the endoplasmic reticulum in the mitochondria-associated membrane fraction that is essential for phospholipid exchange. It was identified as a key player in the phosphatidylglycerol remodeling that is essential for both mitochondrial function and intracellular cholesterol trafficking. Here we report two new Turkish sibling patients affected with MEGDEL syndrome due to SERAC1 gene mutation. The patients were presented with 3-methylglutaconic acid and 3-methylglutaric aciduria, microcephaly, growth retardation, dysmorphic features, severe sensorineural deafness, progressive spasticity, dystonia, seizures, basal ganglia involvement. Metabolic acidosis, mild hyperammonemia and lactic acidemia were accompanied with clinical findings in newborn period. PMID- 27186705 TI - Acute colchicine intoxication complicated with complete AV block. AB - Colchicine, is an old and well-known drug, used for treatment of rheumatic diseases. Nausea, vomiting, abdominal pain, and diarrhea are the clinical symptoms of colchicine poisoning. Cardiotoxicity can lead to mortality. We report a case of colchicine intoxication complicated with complete heart block. A 9-year old patient ingesting colchicine 0.4-0.5 mg/kg was transferred because of elevation of liver enzymes, and deterioration of kidney functions and cytopenia. History of colchicine ingestion had been unknown at time of admission. After initial fluid and electrolyte treatment electrolyte imbalance ameliorated but kidney and liver functions worsened. In the third day of admission (7th day of ingestion), she confessed taking colchicine pills. Her state of consciousness became comatose and endotracheal intubation required. She developed complete heart block requiring temporary transvenous pacemaker implantation in the fifth day of admission. One day after pacemaker implantation, cardiopulmonary arrest developed again and remained completely unresponsive to CPR, and died. Cardiotoxicity of colchicine is leading cause of mortality. Tachycardia and conduction anomalies are not rare, but complete AV block in pediatric patient has never been reported. Although underlying mechanism is not known colchicine may have a direct toxic effect on conduction. PMID- 27186706 TI - Optic neuritis as a presenting symptom of Mycoplasma pneumoniae infection. AB - A broad range of neurologic disorders has been described in children infected with Mycoplasma pneumoniae, of which encephalitis is among the most common. In contrast, the association between optic neuritis and Mycoplasma pneumoniae infection has been rarely described in children. We report a case of a 12-year old girl who was seropositive for antibodies against Mycoplasma pneumoniae and presented with optic neuritis without respiratory symptoms or other neurologic findings. PMID- 27186707 TI - Cetirizine and albendazole induced dystonia in a child. AB - Drug-induced dystonic reactions are a common presentation to the Pediatric Emergency Department frequently with antiemetics, antidepressants, dopamineblocking agents and antipyschotics. We report a case of generalized form of dystonia after taking albendazole and cetirizine. There is only one case with albendazole induced and two cases with cetirizine induced dystonia in the literature. PMID- 27186708 TI - A case of xanthogranulomatous pyelonephritis mimicking Wilms tumor. AB - Xanthogranulomatous pyelonephritis (XGPN) is a very rare, unusual variant of pyelonephritis characterized by destruction of renal parenchyma. It usually occurs in adults with a history of recurrent urinary tract infections. The condition is rare in children and the disease can imitate renal tumors. Here, we describe a 12-year-old boy who presented with abdominal pain. He did not have any history of urinary tract infection. Computed tomography and magnetic resonance imaging showed a cystic lesion in the left upper kidney. The patient underwent radical nephrectomy with a provisional diagnosis of Wilms tumor however histopathological examination of specimen revealed XGPN. Xanthogranulomatous pyelonephritis should be kept in mind in the differential diagnosis of renal lesions in childhood, during surgery if any suspicion from the diagnosis, a frozen biopsy should have been taken. PMID- 27186709 TI - Embolization of a complex pulmonary arteriovenous fistula and coarctation treatment with covered stent at the same session. AB - Pulmonary arteriovenous fistula (PAVF) are rare malformations that may cause serious complications such as paradoxical embolism, stroke, pulmonary hemorrhage and hemoptysis. Accompanying cardiac malformations such as aortic coarctation were not reported previously. Here we present a case of complex PAVF associated with aortic coarctation. The patient was treated successfully by transcatheter embolization of PAVF with amplatzer vascular plug I and II and implantation of a covered CP stent for coarctation at the same session. PMID- 27186710 TI - A neonate with intestinal volvulus without malrotation exhibiting early jaundice with a suspected fetal onset. AB - Intestinal volvulus without malrotation is a rare disease that causes volvulus of the small intestine despite normal intestinal rotation and fixation. We encountered a neonate with this disease who developed early jaundice and was suspected to have a fetal onset. This patient was characterized by early jaundice complicating intestinal volvulus without malrotation and is considered to have exhibited reduced fetal movement and early jaundice as a result of volvulus, necrosis, and hemorrhage of the small intestine in the fetal period. If abdominal distention accompanied by early jaundice is noted in a neonate, intestinal volvulus without malrotation and associated intraabdominal hemorrhage should be suspected and promptly treated. PMID- 27186711 TI - Early rehabilitation of a child with intensive care unit acquired weakness secondary to membranoproliferative glomerulonephritis: A case report. AB - Intensive care unit acquired weakness presents with flaccid paralysis of the extremities and difficulty of weaning from the ventilator and it has occasionally been reported in children. We report the early rehabilitation of a 12-year-old girl with membranoproliferative glomerulonephritis who developed intensive care unit acquired weakness. She underwent an intensive rehabilitation procedure which included assistive range of motion, bed mobility, airway clearance and breathing techniques, neuromuscular electrical stimulation (NMES) to the quadriceps muscles and resistive therapeutic band exercises. Following the rehabilitation program, muscle strength (Medical Research Council sum score), ambulation (Functional Ambulation Category) and activity (Wee FIM) scores increased significantly. PMID- 27186712 TI - A tale of 2 ADFs: differences in the effectiveness of abuse-deterrent formulations of oxymorphone and oxycodone extended-release drugs. AB - The introduction of extended-release opioid analgesics helped initiate an epidemic of prescription opioid abuse in the United States. To make access to the drug by crushing or dissolution more difficult, abuse-deterrent formulations (ADFs) of OxyContin (Purdue Pharma, Stamford, CT) and Opana ER (Endo Pharmaceuticals Inc., Malvern, PA), which use the same foundation technology (Intac, Grunenthal, Aachen, Germany), were introduced in 2010 and 2012, respectively. To examine their relative effectiveness, we used a structured survey of 12,124 individuals entering treatment for opioid use disorder followed by a more focused online survey with a subset of these patients (N = 129) using both structured and open-ended questions. Data showed that the OxyContin ADF was highly effective in reducing nonoral abuse (91.4% before the ADF, 47.9% afterwards), particularly with insufflation (78%-28.8%) and intravenous injection of the active drug (42.7%-21.4%). However, although the Opana ER ADF was effective in reducing insufflation (80%-37.1%), injection (60.0%-51.4%), and overall nonoral abuse (94.3%-77.1%), it showed no significant decrease over time. Bearing in mind that the Opana ER sample was smaller in size than that for OxyContin, our results nonetheless suggest disparate outcomes resulting from the introduction of the ADFs, which could indicate that an ADF's effectiveness may be drug-specific. Given the public health impact of prescription opioids and the considerable effort being expended to develop ADFs as a partial solution to the problem, our preliminary studies suggest that each ADF must be evaluated on its own merits even if the same proprietary technology is used. PMID- 27186714 TI - When and how to start prophylaxis in boys with severe hemophilia without inhibitors: communication from the SSC of the ISTH. PMID- 27186713 TI - Dissociation between the relief of skeletal pain behaviors and skin hypersensitivity in a model of bone cancer pain. AB - Recent studies have suggested that in humans and animals with significant skeletal pain, changes in the mechanical hypersensitivity of the skin can be detected. However, whether measuring changes in skin hypersensitivity can be a reliable surrogate for measuring skeletal pain itself remains unclear. To explore this question, we generated skeletal pain by injecting and confining GFP transfected NCTC 2472 osteosarcoma cells unilaterally to the femur of C3H male mice. Beginning at day 7 post-tumor injection, animals were administered vehicle, an antibody to the P2X3 receptor (anti-P2X3) or anti-NGF antibody. Pain and analgesic efficacy were then measured on days 21, 28, and 35 post-tumor injection using a battery of skeletal pain-related behaviors and von Frey assessment of mechanical hypersensitivity on the plantar surface of the hind paw. Animals with bone cancer pain treated with anti-P2X3 showed a reduction in skin hypersensitivity but no attenuation of skeletal pain behaviors, whereas animals with bone cancer pain treated with anti-NGF showed a reduction in both skin hypersensitivity and skeletal pain behaviors. These results suggest that although bone cancer can induce significant skeletal pain-related behaviors and hypersensitivity of the skin, relief of hypersensitivity of the skin is not always accompanied by attenuation of skeletal pain. Understanding the relationship between skeletal and skin pain may provide insight into how pain is processed and integrated and help define the preclinical measures of skeletal pain that are predictive end points for clinical trials. PMID- 27186716 TI - Divide and conquer: Salmonella move into both daughter cells during mitosis. PMID- 27186717 TI - Neurochemical biomarkers in the diagnosis of frontotemporal lobar degeneration: an update. AB - Frontotemporal lobar degeneration (FTLD) is a spectrum of rare neurodegenerative diseases with overlapping symptoms and neuropathology. It includes the behavioral variant of frontotemporal dementia (bvFTD), the semantic and non-fluent variant of primary progressive aphasia (svPPA and nfvPPA), FTD with motor neuron disease (FTD-MND), progressive supranuclear palsy, and corticobasal syndrome. The diagnosis of the FTLD spectrum of diseases is based on clinical symptoms which hampers the differentiation of the diseases among each other and with other disorders that show a similar clinical appearance resulting in a high rate of misdiagnoses. This highlights the need for objective and selective measures in the diagnostic criteria and there is extensive research on neurochemical biomarkers in FTLD as one option to address this unmet clinical need. Here, we review the advances in CSF biomarker research in FTLD in the last 2 years with regard to the validation of previously suggested and identification of new biomarker candidates for the differential diagnosis of FTLD. New biomarkers for frontotemporal lobar degeneration (FTLD) are urgently needed to support differential diagnosis within the disease spectrum and with related neurodegenerative diseases such as Alzheimer disease (AD). Here, we review the advances in cerebrospinal fluid biomarker research in FTLD and provide a list of promising candidate markers. PMID- 27186718 TI - Facile Cell Sheet Harvest and Translocation Mediated by a Thermally Expandable Hydrogel with Controlled Cell Adhesion. AB - Facile cell sheet translocation system is developed based on a thermally expandable hydrogel with modular cell adhesion favorable for both robust cell sheet formation and harvest. Efficient translocation is achieved at moderate cell substrate interaction, which can be tuned by two-step reactions of mussel inspired coating. PMID- 27186715 TI - The impact of prescribed opioids on CD4 cell count recovery among HIV-infected patients newly initiating antiretroviral therapy. AB - OBJECTIVES: Certain prescribed opioids have immunosuppressive properties, yet their impact on clinically relevant outcomes, including antiretroviral therapy (ART) response among HIV-infected patients, remains understudied. METHODS: Using the Veterans Aging Cohort Study data, we conducted a longitudinal analysis of 4358 HIV-infected patients initiating ART between 2002 and 2010 and then followed them for 24 months. The primary independent variable was prescribed opioid duration, categorized using pharmacy data as none prescribed, short-term (< 90 days) and long-term (>= 90 days). Outcomes included CD4 cell count over time. Analyses adjusted for demographics, comorbid conditions, ART type and year of initiation, and overall disease severity [ascertained with the Veterans Aging Cohort Study (VACS) Index]. Sensitivity analyses examined whether effects varied according to baseline CD4 cell count, achievement of viral load suppression, and opioid properties (i.e. dose and known immunosuppressive properties). RESULTS: Compared to those with none, patients with short-term opioids had a similar increase in CD4 cell count (mean rise per year: 74 vs. 68 cells/MUL; P = 0.11), as did those with long-term prescribed opioids (mean rise per year: 74 vs. 75 cells/MUL; P = 0.98). In sensitivity analysis, compared with no opioids, the effects of short-term prescribed opioids were statistically significant among those with a baseline CD4 cell count >= 500 cells/MUL (mean rise per year: 52 cells/MUL for no opioids vs. 20 cells/MUL for short-term opioids; P = 0.04); findings were otherwise unchanged. CONCLUSIONS: Despite immunosuppressive properties intrinsic to opioids, prescribed opioids appeared to have no effect on CD4 cell counts over 24 months among HIV-infected patients initiating ART. PMID- 27186720 TI - Re: Partial vs Radical Nephrectomy for T1 Renal Tumours: An Analysis from the British Association of Urological Surgeons Nephrectomy Audit. PMID- 27186719 TI - Nicotinamide phosphoribosyltransferase (Nampt) in carcinogenesis: new clinical opportunities. AB - INTRODUCTION: Nicotinamide phosphoribosyltransferase (Nampt) is the rate-limiting enzyme that catalyzes the first step in the mammalian nicotinamide adenine dinucleotide (NAD) salvage pathway. Aberrant NAD metabolism was associated with oncogenic signal transduction, suggesting the critical roles of Nampt in tumorigenesis and metastasis. Additionally, Nampt can be secreted out of the cell, and this extracellular form of Nampt (eNampt) was shown to induce inflammation and angiogenesis due to its cytokine activity, which may also be involved in carcinogenesis. AREAS COVERED: This article reviews recent advances in the studies of Nampt in carcinogenesis, with a special highlight on Nampt inhibitors and future clinical application, including cancer diagnosis, prognosis and therapy. Expert commentary: Nampt not only maintains the balance of cellular metabolism, but also has a profound influence on multiple aspects of carcinogenesis. Therefore, elucidation of these mechanisms opens the door for future clinical applications targeting this protein. Additional studies are needed to address important questions including the relationship between extracellular Nampt and carcinogenesis. PMID- 27186721 TI - Re: Renal Tumor Biopsy for Small Renal Masses: A Single-Center 13-Year Experience. PMID- 27186722 TI - Re: Recurrence Patterns after Open and Robot-Assisted Radical Cystectomy for Bladder Cancer. PMID- 27186723 TI - Re: Radiofrequency Ablation of Functioning Adrenal Adenomas: Preliminary Clinical and Laboratory Findings. PMID- 27186724 TI - Re: Small (< 4 cm) Renal Masses: Differentiation of Angiomyolipoma without Visible Fat from Renal Cell Carcinoma Using Unenhanced and Contrast-Enhanced CT. PMID- 27186725 TI - Re: Solid Renal Cell Carcinoma Measuring Water Attenuation (-10 to 20 HU) on Unenhanced CT. PMID- 27186726 TI - Re: Oncologic Outcomes following Robot-Assisted Radical Cystectomy with Minimum 5 Year Follow-up: The Roswell Park Cancer Institute Experience. PMID- 27186727 TI - Re: Prognostic Factors and Risk Groups in T1G3 Non-Muscle-Invasive Bladder Cancer Patients Initially Treated with bacillus Calmette-Guerin: Results of a Retrospective Multicenter Study of 2451 Patients. PMID- 27186728 TI - Re: Long-Term Follow-up of a Randomized Trial of Radiation with or without Androgen Deprivation Therapy for Localized Prostate Cancer. PMID- 27186729 TI - Re: Androgen Receptor Splice Variant 7 and Efficacy of Taxane Chemotherapy in Patients with Metastatic Castration-Resistant Prostate Cancer. PMID- 27186730 TI - Re: Impact of a Genomic Classifier of Metastatic Risk on Postprostatectomy Treatment Recommendations by Radiation Oncologists and Urologists. PMID- 27186731 TI - Re: Trends in Prostate-Specific Antigen Screening, Prostate Biopsies, Urology Visits, and Prostate Cancer Treatments from 2000 to 2012. PMID- 27186732 TI - Re: Diclofenac Suppository as a Preemptive Analgesia in Ultrasound-Guided Biopsy of Prostate: Randomized Controlled Trial. PMID- 27186733 TI - Re: Role of Surgical Resection for Refractory Germ Cell Tumors. PMID- 27186734 TI - Re: EAU Guidelines on Penile Cancer: 2014 Update. PMID- 27186735 TI - Re: Modular Flexible Ureteroscopy and Holmium Laser Lithotripsy for the Treatment of Renal and Proximal Ureteral Calculi: A Single-Surgeon Experience of 382 Cases. PMID- 27186736 TI - Re: Impact of Retrograde Flexible Ureteroscopy and Intracorporeal Lithotripsy on Kidney Functional Outcomes. PMID- 27186737 TI - Re: The Efficacy of Peritubal Analgesic Infiltration in Postoperative Pain following Percutaneous Nephrolithotomy-A Prospective Randomized Controlled Study. PMID- 27186738 TI - Re: Age-Related Delay in Urinary Stone Clearance in Elderly Patients with Solitary Proximal Ureteral Calculi Treated by Extracorporeal Shock Wave Lithotripsy. PMID- 27186739 TI - Re: Tubeless versus Standard PCNL in Geriatric Population. PMID- 27186741 TI - Re: Outcomes of the Endoscopic Treatment of Bladder Neck Contractures in the Orthotopic Neobladder. PMID- 27186740 TI - Re: The Surgical Learning Curve for One-Stage Anterior Urethroplasty: A Prospective Single-Surgeon Study. PMID- 27186742 TI - Re: Long-Term Artificial Urinary Sphincter Outcomes following a Prior Rectourethral Fistula Repair. PMID- 27186743 TI - Re: The Prevention and Management of Noninfectious Complications of Penile Implants. PMID- 27186744 TI - Re: Penile Amputation: Cosmetic and Functional Results. PMID- 27186745 TI - Re: How Slow is Too Slow? Correlation of Operative Time to Complications: An Analysis from the Tennessee Surgical Quality Collaborative. PMID- 27186746 TI - Re: Penile Prosthesis First and Replacement Surgeries: Analysis of Patient and Partner Satisfaction. PMID- 27186747 TI - Re: Evaluation of the Treatment of Congenital Penile Curvature including Psychosexual Assessment. PMID- 27186748 TI - Re: Long-Term Changes in Renal Function Outcomes following Radical Cystectomy and Urinary Diversion. PMID- 27186749 TI - Re: Management of Complications of Mesh Surgery. PMID- 27186750 TI - Re: Health-Related Quality of Life and Outcomes after Surgical Treatment of Complications from Vaginally Placed Mesh. PMID- 27186751 TI - Re: Long-Term Functional Outcomes after Artificial Urinary Sphincter Implantation in Men with Stress Urinary Incontinence. PMID- 27186752 TI - Re: Creating a Gold Standard Surgical Procedure: The Development and Implementation of TVT: Ulf Ulmsten Memorial Lecture 2014. PMID- 27186753 TI - Re: Involvement of beta3-Adrenoceptors in the Inhibitory Control of Cholinergic Activity in Human Bladder: Direct Evidence by [3H]-Acetylcholine Release Experiments in the Isolated Detrusor. PMID- 27186754 TI - Re: Conversion of Urodynamic Pressures Measured Simultaneously by Air-Charged and Water-Filled Catheter Systems. PMID- 27186755 TI - Re: Risk Factors for Recurrence after Le Fort Colpocleisis for Severe Pelvic Organ Prolapse in Elderly Women. PMID- 27186756 TI - Re: Underweight Body Mass Index is a Risk Factor of Mortality in Outpatients with Nocturia in Japan. PMID- 27186757 TI - Re: The Risk of Fall and Fracture with the Initiation of a Prostate-Selective alpha Antagonist: A Population Based Cohort Study. PMID- 27186759 TI - Re: Analyzing why Men Seek Treatment for Lower Urinary Tract Symptoms and Factors Associated with Nonimprovement. PMID- 27186758 TI - Re: Impact of Metabolic Syndrome on Response to Medical Treatment of Benign Prostatic Hyperplasia. PMID- 27186760 TI - Re: Treatment of Benign Prostatic Hyperplasia Using Transurethral Split of the Prostate with a Columnar Balloon Catheter. PMID- 27186761 TI - Re: When One Becomes More: Minimum Renal Artery Length in Laparoscopic Live Donor Nephrectomy. PMID- 27186763 TI - Re: Therapeutic Hypothermia in Deceased Organ Donors and Kidney-Graft Function. PMID- 27186762 TI - Re: Unintended Consequences of the New National Kidney Allocation Policy in the United States. PMID- 27186764 TI - Re: Comparative Analysis of Tunical Plication vs. Intralesional Injection Therapy for Ventral Peyronie's Disease. PMID- 27186765 TI - Re: Topical Treatment for Acute Phase Peyronie's Disease Utilizing a New Gel, H 100: A Randomized, Prospective, Placebo-Controlled Pilot Study. PMID- 27186766 TI - Re: An Analysis of Case Logs from American Urologists in the Treatment of Peyronie's Disease. PMID- 27186767 TI - Re: Psychological Treatment Trials for Hypoactive Sexual Desire Disorder: A Sexual Medicine Critique and Perspective. PMID- 27186768 TI - Re: Women's Endorsement of Models of Sexual Response: Correlates and Predictors. PMID- 27186769 TI - Re: Comparison of Microdissection Testicular Sperm Extraction, Conventional Testicular Sperm Extraction, and Testicular Sperm Aspiration for Nonobstructive Azoospermia: A Systematic Review and Meta-Analysis. PMID- 27186770 TI - Re: Salvage Micro-Dissection Testicular Sperm Extraction; Outcome in Men with Non Obstructive Azoospermia with Previous Failed Sperm Retrievals. PMID- 27186771 TI - Re: Outcomes of Microdissection Testicular Sperm Extraction in Men with Nonobstructive Azoospermia Due to Maturation Arrest. PMID- 27186772 TI - Re: Single Human Sperm Cryopreservation Method Using Hollow-Core Agarose Capsules. PMID- 27186773 TI - Re: Fourteen Babies Born after Round Spermatid Injection into Human Oocytes. PMID- 27186774 TI - Re: Tracking Trends in Provider Reimbursements and Patient Obligations. PMID- 27186775 TI - Re: Trends in National Institutes of Health Funding for Clinical Trials Registered in ClinicalTrials.gov. PMID- 27186776 TI - Re: Changes in Burnout and Satisfaction with Work-Life Balance in Physicians and the General US Working Population between 2011 and 2014. PMID- 27186777 TI - Re: Utility of the Distal Ureteral Diameter on VCUG for Grading VUR. PMID- 27186778 TI - Re: Predictive Value of Specific Ultrasound Findings when Used as a Screening Test for Abnormalities on VCUG. PMID- 27186779 TI - Re: Imaging and Surgical Utilization for Pediatric Cystinuria Patients: A Single Institution Cohort Study. PMID- 27186780 TI - Re: Safety and Efficacy of Staged Pelvic Osteotomies in the Modern Treatment of Cloacal Exstrophy. PMID- 27186781 TI - Re: Abdominal Wall Dysfunction in Adult Bladder Exstrophy: A Treatable but Under Recognized Problem. PMID- 27186782 TI - Re: RNA-Seq of Single Prostate CTCs Implicates Noncanonical Wnt Signaling in Antiandrogen Resistance. PMID- 27186783 TI - Re: AKAP3 Degradation in Sperm Capacitation is Regulated by its Tyrosine Phosphorylation. PMID- 27186784 TI - Re: Tumour-Suppressive MicroRNA-29s Directly Regulate LOXL2 Expression and Inhibit Cancer Cell Migration and Invasion in Renal Cell Carcinoma. PMID- 27186786 TI - N-acetylcysteine eradicates Pseudomonas aeruginosa biofilms in bone cement. AB - Biofilm is an example of bacterial group behavior. We investigated the effect of N-acetylcysteine (NAC) alone and in combination with ciprofloxacin on Pseudomonas aeruginosa biofilm formation. Four groups (each contains six molds) of standardized bone cement molds were infected. NAC, ciprofloxacin each alone, and NAC/ciprofloxacin combination were evaluated in point of inhibiting and eradicating biofilm capacity using microbiological and electron microscopical evaluation techniques. Microbial counts and electron microscopical observations showed that the effect of NAC and ciprofloxacin combination on biofilm formation in bone cement is valuable. NAC enhances the beneficial effect of ciprofloxacin when used in combination with it in bone cement. SCANNING 38:766-770, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27186787 TI - Controlled Permeability in Porous Polymer Nanocapsules Enabling Size- and Charge Selective SERS Nanoprobes. AB - Nanoprobes for surface-enhanced Raman scattering (SERS) were prepared by creating nanorattles, or yolk-shell structures, containing gold or silver nanoparticles entrapped in porous hollow polymer nanocapsules. Controlled permeability of the shells of nanocapsules, achieved by controlling the pore size and/or shell surface functionalization, resulted in size- and charge-selective SERS analyses. For example, a trace amount of phenanthroline, a model analyte, was detected in human blood plasma without preprocessing of plasma samples. Comparison with commercially available nanoparticles showed superior performance of the newly prepared nanorattle structures. PMID- 27186788 TI - Potential role for psychological skills training in emergency medicine: Part 1 - Introduction and background. AB - Psychological skills training (PST) is the systematic acquisition and practice of different psychological techniques to improve cognitive and technical performance. This training consists of three phases: education, skills acquisition and practice. Some of the psychological skills developed in this training include relaxation techniques, focusing and concentration skills, positive 'self-suggestion' and visualisation exercises. Since the middle of the 20th century, PST has been successfully applied by athletes, performing artists, business executives, military personnel and other professionals in high-risk occupations. Research in these areas has demonstrated the breadth and depth of the training's effectiveness. Despite the benefits realised in other professions, medicine has only recently begun to explore certain elements of PST. The present paper reviews the history and evidence behind the concept of PST. In addition, it presents some aspects of PST that have already been incorporated into medical training as well as implications for developing more comprehensive programmes to improve delivery of emergency medical care. PMID- 27186789 TI - Atomized Human Amniotic Mesenchymal Stromal Cells for Direct Delivery to the Airway for Treatment of Lung Injury. AB - BACKGROUND: Current treatment regimens for inhalation injury are mainly supportive and rely on self-regeneration processes for recovery. Cell therapy with mesenchymal stromal cells (MSCs) is increasingly being investigated for the treatment of inhalation injury. Human amniotic MSCs (hAMSCs) were used in this study due to their potential use in inflammatory and fibrotic conditions of the lung. This study aimed at demonstrating that hAMSCs can be atomized with high viability, for the purpose of achieving a more uniform distribution of cells throughout the lung. Another aim of this study was to set ground for future application to healthy and diseased lungs by demonstrating that hAMSCs were able to survive after being sprayed onto substrates with different stiffness. METHODS: Two methods of atomization were evaluated, and the LMA MAD780 device was selected for atomizing hAMSCs for optimized delivery. To mimic the stiffness of healthy and diseased lungs, gelatin gel (10% w/v) and tissue culture plastic were used as preliminary models. Poly-l-lysine (PLL) and collagen I coatings were used as substrates on which the hAMSCs were cultured after being sprayed. RESULTS: The feasibility of atomizing hAMSCs was demonstrated with high cell viability (81 +/- 3.1% and 79 +/- 11.6% for cells sprayed onto plastic and gelatin, respectively, compared with 85 +/- 4.8% for control/nonsprayed cells) that was unaffected by the different stiffness of substrates. The presence of the collagen I coating on which the sprayed cells were cultured yielded higher cell proliferation compared with both PLL and no coating. The morphology of sprayed cells was minimally compromised in the presence of the collagen I coating. CONCLUSIONS: This study demonstrated that hAMSCs are able to survive after being sprayed onto substrates with different stiffness, especially in the presence of collagen I. Further studies may advance the effectiveness of cell therapy for lung regeneration. PMID- 27186790 TI - In Situ Catalyst Modification in Atom Transfer Radical Reactions with Ruthenium Benzylidene Complexes. AB - Ruthenium benzylidene complexes are well-known as olefin metathesis catalysts. Several reports have demonstrated the ability of these catalysts to also facilitate atom transfer radical (ATR) reactions, such as atom transfer radical addition (ATRA) and atom transfer radical polymerization (ATRP). However, while the mechanism of olefin metathesis with ruthenium benzylidenes has been well studied, the mechanism by which ruthenium benzylidenes promote ATR reactions remains unknown. To probe this question, we have analyzed seven different ruthenium benzylidene complexes for ATR reactivity. Kinetic studies by (1)H NMR revealed that ruthenium benzylidene complexes are rapidly converted into new ATRA active, metathesis-inactive species under typical ATRA conditions. When ruthenium benzylidene complexes were activated prior to substrate addition, the resulting activated species exhibited enhanced kinetic reactivity in ATRA with no significant difference in overall product yield compared to the original complexes. Even at low temperature, where the original intact complexes did not catalyze the reaction, preactivated catalysts successfully reacted. Only the ruthenium benzylidene complexes that could be rapidly transformed into ATRA active species could successfully catalyze ATRP, whereas other complexes preferred redox-initiated free radical polymerization. Kinetic measurements along with additional mechanistic and computational studies show that a metathesis inactive ruthenium species, generated in situ from the ruthenium benzylidene complexes, is the active catalyst in ATR reactions. Based on data from (1) H, (13)C, and (31)P NMR spectroscopy and X-ray crystallography, we suspect that this ATRA-active species is a RuxCly(PCy3)z complex. PMID- 27186791 TI - Arsenic Speciation in Bituminous Coal Fly Ash and Transformations in Response to Redox Conditions. AB - The risk of the mobilization of coal ash into the environment has highlighted the need for the assessment of the environmental behavior of coal ash, particularly with respect to toxic trace elements such as arsenic (As). Here, we examined As speciation in coal fly ash samples and transformations in response to aquatic redox conditions. X-ray absorption spectroscopy indicated that 92-97% of total As occurred as As(V), with the remainder present as As(III). Major As-bearing hosts in unamended ashes were glass, iron (oxyhydr)oxides, and calcium arsenate. Oxic leaching resulted in immediate As mobilization to the aqueous phase, reprecipitation of As-iron ferrihydrite, and As adsorption to mineral surfaces. Under anoxic conditions, the (reductive) dissolution of As-bearing phases such as iron ferrihydrite resulted in increased dissolved As compared to oxic conditions and reprecipitation of iron arsenate. Overall, As in coal ash is not environmentally stable and can participate in local biogeochemical cycles. PMID- 27186792 TI - Terlipressin given by continuous intravenous infusion or by intravenous boluses: Is there already an answer? PMID- 27186794 TI - Imaging of Arthroplasties: Improved Image Quality and Lesion Detection With Iterative Metal Artifact Reduction, a New CT Metal Artifact Reduction Technique. AB - OBJECTIVE: The purpose of this study was to compare iterative metal artifact reduction (iMAR), a new single-energy metal artifact reduction technique, with filtered back projection (FBP) in terms of attenuation values, qualitative image quality, and streak artifacts near shoulder and hip arthroplasties and observer ability with these techniques to detect pathologic lesions near an arthroplasty in a phantom model. MATERIALS AND METHODS: Preoperative and postoperative CT scans of 40 shoulder and 21 hip arthroplasties were reviewed. All postoperative scans were obtained using the same technique (140 kVp, 300 quality reference mAs, 128 * 0.6 mm detector collimation) on one of three CT scanners and reconstructed with FBP and iMAR. The attenuation differences in bones and soft tissues between preoperative and postoperative scans at the same location were compared; image quality and streak artifact for both reconstructions were qualitatively graded by two blinded readers. Observer ability and confidence to detect lesions near an arthroplasty in a phantom model were graded. RESULTS: For both readers, iMAR had more accurate attenuation values (p < 0.001), qualitatively better image quality (p < 0.001), and less streak artifact (p < 0.001) in all locations near arthroplasties compared with FBP. Both readers detected more lesions (p <= 0.04) with higher confidence (p <= 0.01) with iMAR than with FBP in the phantom model. CONCLUSION: The iMAR technique provided more accurate attenuation values, better image quality, and less streak artifact near hip and shoulder arthroplasties than FBP; iMAR also increased observer ability and confidence to detect pathologic lesions near arthroplasties in a phantom model. PMID- 27186793 TI - Fishing for Fetal Alcohol Spectrum Disorders: Zebrafish as a Model for Ethanol Teratogenesis. AB - Fetal Alcohol Spectrum Disorders (FASD) describes a wide array of ethanol-induced developmental defects, including craniofacial dysmorphology and cognitive impairments. It affects ~1 in 100 children born in the United States each year. Due to the pleiotropic effects of ethanol, animal models have proven critical in characterizing the mechanisms of ethanol teratogenesis. In this review, we focus on the utility of zebrafish in characterizing ethanol-induced developmental defects. A growing number of laboratories have focused on using zebrafish to examine ethanol-induced defects in craniofacial, cardiac, ocular, and neural development, as well as cognitive and behavioral impairments. Growing evidence supports that genetic predisposition plays a role in these ethanol-induced defects, yet little is understood about these gene-ethanol interactions. With a high degree of genetic amenability, zebrafish is at the forefront of identifying and characterizing the gene-ethanol interactions that underlie FASD. Because of the conservation of gene function between zebrafish and humans, these studies will directly translate to studies of candidate genes in human populations and allow for better diagnosis and treatment of FASD. PMID- 27186795 TI - Oral versus vaginal prostaglandin for labor induction. AB - OBJECTIVE: To compare the efficacy and safety of oral prostaglandin (PG) in solution versus vaginal PG gel for labor induction. DESIGN: A retrospective study. METHODS: Data from original obstetric records at a university hospital in Sweden 2012-2013. RESULTS: In all women, oral PG resulted in vaginal birth (VB) < 24 h in 66% compared to 80% with vaginal PG (p < 0.001), and cesarean section (CS) in 19% versus 32% (p = 0.02). In primiparous women, oral PG was followed by VB <24 h in 54% compared to 71% (p = 0.01), and CS in 25% versus 41% (p = 0.03). In women with an unripe cervix, oral PG lead to VB <24 h in 66% compared to 79% (p = 0.01), and CS in 21% versus 33% (p = 0.04). Despite a longer induction to vaginal delivery interval with oral PG, the rates of obstetric bleeding, chorioamnionitis, and neonatal asphyxia were not increased. CONCLUSIONS: Oral PG in solution was less effective than vaginal PG gel in achieving VB <24 h. However, oral PG was safer, since it resulted in fewer CSs without increasing maternal morbidity or neonatal asphyxia. PMID- 27186796 TI - Metabolic disposition and biological significance of simple phenols of dietary origin: hydroxytyrosol and tyrosol. AB - Hydroxytyrosol and tyrosol are dietary phenolic compounds present in virgin olive oil and wine. Both compounds are also endogenously synthesized in our body as byproducts of dopamine and tyramine metabolisms, respectively. Over the last decades, research into hydroxytyrosol and tyrosol has experienced an increasing interest due to the role that these compounds may play in the prevention of certain pathologies (e.g. cardiovascular, metabolic, neurodegenerative diseases and cancer). The translation of promising in vitro and in vivo biological effects from preclinical studies to the context of human disease prevention initially depends on whether the dose ingested becomes available at the site of action. In this regard, information regarding the bioavailability and metabolic disposition of hydroxytyrosol and tyrosol is of most importance to evaluate the impact they may have on human health. In this review, we discuss and summarize the state of the art of the scientific evidence regarding the processes of absorption, distribution, metabolism and excretion of both hydroxytyrosol and tyrosol. We also examine the impact of these compounds and their metabolites on biological activity in terms of beneficial health effects. Finally, we evaluate the different analytical approaches that have been developed to measure the plasma and urinary levels of hydroxytyrosol, tyrosol and their metabolites. PMID- 27186797 TI - Reactions of Atmospheric Particulate Stabilized Criegee Intermediates Lead to High-Molecular-Weight Aerosol Components. AB - Aging of organic aerosol particles is one of the most poorly understood topics in atmospheric aerosol research. Here, we used an aerosol flow tube together with an iodide-adduct high-resolution time-of-flight chemical-ionization mass spectrometer equipped with a Filter Inlet for Gases and AEROsols (FIGAERO-HRToF CIMS) to investigate heterogeneous ozonolysis of oleic acid (OL), developing a comprehensive oxidation mechanism with observed products. In addition to the well known first-generation C9 products including nonanal, nonanoic acid, azelaic acid, and 9-oxononanoic acid, the iodide-adduct chemical ionization permitted unambiguous determination of a large number of high-molecular-weight particulate products up to 670 Da with minimum amounts of fragmentation. These high-molecular weight products are characterized by a fairly uniform carbon oxidation state but stepwise addition of a carbon backbone moiety, and hence continuous decrease in the volatility. Our results demonstrate that heterogeneous oxidation of organic aerosols has a significant effect on the physiochemical properties of organic aerosols and that reactions of particulate SCIs from ozonolysis of an unsaturated particulate species represent a previously underappreciated mechanism that lead to formation of high-molecular-weight particulate products that are stable under typical atmospheric conditions. PMID- 27186798 TI - Association between asthma and dysphonia: A population-based study. AB - OBJECTIVE: We investigated whether asthma predisposes patients to organic laryngeal lesions or increases dysphonia in those without organic laryngeal lesions. METHODS: We performed a cross-sectional study with data from the Korea National Health and Nutrition Examination Survey; 19,330 subjects from 2008 through 2011 were included. The associations of asthma with organic laryngeal lesions and dysphonia were analyzed using a simple/multiple logistic regression analysis with complex sampling while adjusting for confounding factors (age, sex, smoking status, stress level, and body mass index) that could contribute to dysphonia. RESULTS: Compared with non-asthma participants, the asthma patients tended to be older and female and to have higher stress levels. These factors were associated with dysphonia (Age, AOR = 1.20, 95% CI = 1.14 = 1.23, P < 0.001; female, AOR = 1.70, 95% CI = 1.33-2.17, P < 0.001; higher stress, AOR = 1.44, 95% CI = 1.23-1.69, P < 0.001). Asthma itself was also associated with dysphonia. Compared with non-asthma participants, asthma patients who had not taken asthma medication recently showed a higher AOR (1.62; 95% CI = 1.0-2.42) for dysphonia, and asthma patients who had taken asthma medication recently showed the highest adjusted odds ratio for dysphonia (AOR = 1.97; 95% confidence interval, CI = 1.28 3.02, P = 0.001). On multiple logistic regression analysis, vocal nodules, laryngeal polyps, and laryngitis were not associated with asthma (all P > 0.05). CONCLUSIONS: Asthma patients are predisposed to subjective dysphonia due to demographic and clinical characteristics (older age, female, and higher stress level) as well as to asthma itself. However, asthma was not associated with organic laryngeal lesions in this study. PMID- 27186800 TI - Strong and Tunable Spin-Orbit Coupling in a Two-Dimensional Hole Gas in Ionic Liquid Gated Diamond Devices. AB - Hydrogen-terminated diamond possesses due to transfer doping a quasi-two dimensional (2D) hole accumulation layer at the surface with a strong, Rashba type spin-orbit coupling that arises from the highly asymmetric confinement potential. By modulating the hole concentration and thus the potential using an electrostatic gate with an ionic-liquid dielectric architecture the spin-orbit splitting can be tuned from 4.6-24.5 meV with a concurrent spin relaxation length of 33-16 nm and hole sheet densities of up to 7.23 * 10(13) cm(-2). This demonstrates a spin-orbit interaction of unprecedented strength and tunability for a 2D hole system at the surface of a wide band gap semiconductor. With a spin relaxation length that is experimentally accessible using existing nanofabrication techniques, this result suggests that hydrogen-terminated diamond has great potential for the study and application of spin transport phenomena. PMID- 27186799 TI - Greazy: Open-Source Software for Automated Phospholipid Tandem Mass Spectrometry Identification. AB - Lipid identification from data produced with high-throughput technologies is essential to the elucidation of the roles played by lipids in cellular function and disease. Software tools for identifying lipids from tandem mass (MS/MS) spectra have been developed, but they are often costly or lack the sophistication of their proteomics counterparts. We have developed Greazy, an open source tool for the automated identification of phospholipids from MS/MS spectra, that utilizes methods similar to those developed for proteomics. From user-supplied parameters, Greazy builds a phospholipid search space and associated theoretical MS/MS spectra. Experimental spectra are scored against search space lipids with similar precursor masses using a peak score based on the hypergeometric distribution and an intensity score utilizing the percentage of total ion intensity residing in matching peaks. The LipidLama component filters the results via mixture modeling and density estimation. We assess Greazy's performance against the NIST 2014 metabolomics library, observing high accuracy in a search of multiple lipid classes. We compare Greazy/LipidLama against the commercial lipid identification software LipidSearch and show that the two platforms differ considerably in the sets of identified spectra while showing good agreement on those spectra identified by both. Lastly, we demonstrate the utility of Greazy/LipidLama with different instruments. We searched data from replicates of alveolar type 2 epithelial cells obtained with an Orbitrap and from human serum replicates generated on a quadrupole-time-of-flight (Q-TOF). These findings substantiate the application of proteomics derived methods to the identification of lipids. The software is available from the ProteoWizard repository: http://tiny.cc/bumbershoot-vc12-bin64 . PMID- 27186801 TI - Piceatannol increases the expression of hepatocyte growth factor and IL-10 thereby protecting hepatocytes in thioacetamide-induced liver fibrosis. AB - Piceatannol is a polyphenolic analog of resveratrol that selectively inhibits the non-receptor tyrosine kinase-Syk. This study investigates the potential ability of piceatannol to attenuate liver fibrosis and protect hepatocytes from injury. Thioacetamide was injected in adult male mice (100 mg/kg, i.p., 3 times/week) for 8 weeks. Piceatannol (1 or 5 mg/kg per day) was administered by oral gavage during the last 4 weeks. Liver function biomarkers, tissue malondialdehyde (MDA), cytokeratin-18 (CK18), hepatocyte growth factor (HGF), and interleukin-10 (IL-10) were measured. Necroinflammation, fibrosis, expression of transforming growth factor (TGF)-beta1, and alpha-smooth muscle actin (SMA) were scored by histopathological examination and immunohistochemistry. Obtained results showed ability of piceatannol (1 mg/kg) to restore liver function and reduce inflammation. It significantly (p < 0.001) reduced MDA, CK18, TGF-beta1, and alpha-SMA expression, and increased HGF and IL-10. It can be concluded that piceatannol at low dose can inhibit TGF-beta1 induced hepatocytes apoptosis and exerts an anti-inflammatory effect attenuating fibrosis progression. PMID- 27186802 TI - Switching of Slow Magnetic Relaxation Dynamics in Mononuclear Dysprosium(III) Compounds with Charge Density. AB - The symmetry around a Dy ion is recognized to be a crucial parameter dictating magnetization relaxation dynamics. We prepared two similar square-antiprismatic complexes, [Dy(LOMe)2(H2O)2](PF6) (1) and Dy(LOMe)2(NO3) (2), where LOMe = [CpCo{P(O)(O(CH3))2}3], including either two neutral water molecules (1) or an anionic nitrate ligand (2). We demonstrated that in this case relaxation dynamics is dramatically affected by the introduction of a charged ligand, stabilizing the easy axis of magnetization along the nitrate direction. We also showed that the application of either a direct-current field or chemical dilution effectively stops quantum tunneling in the ground state of 2, thereby increasing the relaxation time by over 3 orders of magnitude at 3.5 K. PMID- 27186803 TI - Microvascular fluid cup: sturdy in the healthy, but bottomless in septic shock. PMID- 27186805 TI - Electric-Field-Induced Nanoscale Surface Patterning in Mexylaminotriazine Functionalized Molecular Glass Derivatives. AB - Nanoscale surface patterns were observed in thin films of mexylaminotriazine functionalized glasses containing polar groups upon the application of an electric field at temperatures over their glass transition temperatures (Tg). This phenomenon occurred due to the surface deformation process initiated by external electric field instabilities on the films. The minimal surface deformation temperature (Tdewet) relative to Tg was found to increase as a function of the polarity of the substituents and the surface pattern roughness was observed to increase linearly with temperature for a fixed electric field and exposure time. Reversal of the electrical field polarity and the use of both hydrophilic and hydrophobic substrates did not significantly change the surface deformation behavior of the films, which is due to the deposition of charges at the free interface. The application of a mask between the electric field electrodes allowed to selectively pattern areas that are exposed. Furthermore, it was observed that this surface deformation behavior was reversible, since heating the films to a temperature above Tg in the absence of an electric field caused the erasure of all surface patterns. PMID- 27186806 TI - Tetrahydroquinolines via Stereospecific [3 + 3]-Annulation of Donor-Acceptor Cyclopropanes with Nitrosoarenes. AB - A stereospecific [3 + 3]-annulation of donor-acceptor cyclopropanes with nitrosoarenes under the influence of MgBr2 as a stoichiometric Lewis acid and reagent offers a novel approach to various structurally diverse C-8-brominated tetrahydroquinolines. In these cascades C-C, C-N, and C-Br bonds are formed. The reactions are easy to conduct and proceed under mild conditions, and the products can readily be further functionalized, rendering the method highly valuable. PMID- 27186807 TI - Anti-Food Allergic Activity of Sulfated Polysaccharide from Gracilaria lemaneiformis is Dependent on Immunosuppression and Inhibition of p38 MAPK. AB - Polysaccharides from Gracilaria lemaneiformis in particular possess various bioactive functions, but their antiallergic activity remains incompletely defined. Sulfated polysaccharide from Gracilaria lemaneiformis (GLSP) was obtained by water extraction and ethanol precipitation followed by column chromatography. BALB/c mice, RBL-2H3, and KU812 cells were used for verifying the anti food allergic activity of GLSP. According to the results of mice experiment, GLSP was able to alleviate allergy symptoms, to reduce TM-specific IgE and IgG1, to suppress Th2 cell polarization, and to promote the function of regulatory T (Treg) cells. In addition, GLSP had the ability to inhibit the function of RBL 2H3 cells. Furthermore, GLSP inhibited the activation of KU812 via suppression of p38 mitogen-activated protein kinase (MAPK). In conclusion, immunosuppression as well as the reduction in the level of p38 MAPK may contribute to GLSP's putative activity against food allergy. GLSP may be used as a functional food component for allergic patients. PMID- 27186809 TI - The impact of updated NICE guidelines on biologic treatment of ulcerative colitis: reflections on past practices, the changing present and implications for the future. PMID- 27186808 TI - Peptoid Library Agar Diffusion (PLAD) Assay for the High-Throughput Identification of Antimicrobial Peptoids. AB - Rapid emergence of antimicrobial resistant organisms necessitates equally rapid methods for the development of new antimicrobial compounds. Of recent interest have been mimics of antimicrobial peptides known as antimicrobial peptoids, which exhibit similar potency to the former but with improved proteolytic stability. Presented herein is a high-throughput method to screen libraries of antimicrobial peptoids immobilized on beads embedded into solid media. Termed the peptoid library agar diffusion (PLAD) assay, this assay allows for individual chemical manipulation of two identical peptoid strands. One strand can be released to diffuse out from a solid support bead and interact with the microorganism during screening. The other strand can be cleaved after screening from beads showing strong antimicrobial activity and analyzed by mass spectrometry to deconvolute the structure of the peptoid. This method was applied to a small library of peptoids to identify an antimicrobial peptoid with modest efficacy against the ESKAPE pathogens. PMID- 27186804 TI - Modeling Molecular Interactions in Water: From Pairwise to Many-Body Potential Energy Functions. AB - Almost 50 years have passed from the first computer simulations of water, and a large number of molecular models have been proposed since then to elucidate the unique behavior of water across different phases. In this article, we review the recent progress in the development of analytical potential energy functions that aim at correctly representing many-body effects. Starting from the many-body expansion of the interaction energy, specific focus is on different classes of potential energy functions built upon a hierarchy of approximations and on their ability to accurately reproduce reference data obtained from state-of-the-art electronic structure calculations and experimental measurements. We show that most recent potential energy functions, which include explicit short-range representations of two-body and three-body effects along with a physically correct description of many-body effects at all distances, predict the properties of water from the gas to the condensed phase with unprecedented accuracy, thus opening the door to the long-sought "universal model" capable of describing the behavior of water under different conditions and in different environments. PMID- 27186810 TI - The Raman-Derived Carbonization Continuum: A Tool to Select the Best Preserved Molecular Structures in Archean Kerogens. AB - The search for indisputable traces of life in Archean cherts is of prime importance. However, their great age and metamorphic history pose constraints on the study of molecular biomarkers. We propose a quantitative criterion to document the thermal maturity of organic matter in rocks in general, and Archean rocks in particular. This is definitively required to select the best candidates for seeking non-altered sample remnants of life. Analysis of chemical (Raman spectroscopy, (13)C NMR, elemental analysis) and structural (HRTEM) features of Archean and non-Archean carbonaceous matter (CM) that was submitted to metamorphic grades lower than, or equal to, that of greenschist facies showed that these features had all undergone carbonization but not graphitization. Raman derived quantitative parameters from the present study and from literature spectra, namely, R1 ratio and FWHM-D1, were used to draw a carbonization continuum diagram showing two carbonization stages. While non-Archean samples can be seen to dominate the first stage, the second stage mostly consists of the Archean samples. In this diagram, some Archean samples fall at the boundary with non-Archean samples, which thus demonstrates a low degree of carbonization when compared to most Archean CM. As a result, these samples constitute candidates that may contain preserved molecular signatures of Archean CM. Therefore, with regard to the search for the oldest molecular traces of life on Earth, we propose the use of this carbonization continuum diagram to select the Archean CM samples. KEY WORDS: Archean-Early life-Kerogen-Raman spectroscopy-Carbonization. Astrobiology 16, 407-417. PMID- 27186821 TI - Usnic Acid Derivatives with Cytotoxic and Antifungal Activities from the Lichen Usnea longissima. AB - Eight usnic acid derivatives, that is, usenamines A-F (1-6), usone (7), and isousone (8), together with the known (+)-usnic acid (9), were isolated from the lichen Usnea longissima. Their structures were elucidated using 1D and 2D NMR and MS data, and the absolute configurations of compounds 1 and 2 were defined by single-crystal X-ray diffraction analyses. Compounds 1, 2, and 8 showed inhibitory effects on the growth of human hepatoma HepG2 cells with IC50 values of 6.0-53.3 MUM compared with methotrexate as the positive control, which had an IC50 value of 15.8 MUM. Furthermore, 1 induced apoptosis of HepG2 cells in a dose dependent manner at concentrations of 0-15.0 MUM. The isolated compounds were also evaluated for their antifungal and antibacterial activities, with 7 and 8 exhibiting weak inhibitory effects on fungal Trichophyton rubrum spp. with an MIC value of 41.0 MUM. PMID- 27186822 TI - Clinical Outcomes of 1 kHz Subperception Spinal Cord Stimulation in Implanted Patients With Failed Paresthesia-Based Stimulation: Results of a Prospective Randomized Controlled Trial. AB - BACKGROUND: Pain relief via spinal cord stimulation (SCS) has historically revolved around producing paresthesia to replace pain, with success measured by the extent of paresthesia-pain overlap. In a recent murine study, by Shechter et al., showed the superior efficacy of high frequency SCS (1 kHz and 10 kHz) at inhibiting the effects of mechanical hypersensitivity compared to sham or 50 Hz stimulation. In the same study, authors report there were no differences in efficacy between 1 kHz and 10 kHz delivered at subperception stimulation strength (80% of motor threshold). Therefore, we designed a randomized, 2 * 2 crossover study of low frequency supra-perception SCS vs. subperception SCS at 1 kHz frequency in order to test whether subperception stimulation at 1 kHz was sufficient to provide effective pain relief in human subjects. METHODS: Twenty two subjects with SCS, and inadequate pain relief based on numeric pain rating scale (NPRS) scores (>5) were enrolled, and observed for total of seven weeks (three weeks of treatment, one week wash off, and another three weeks of treatment). Subjects were asked to rate their pain on NPRS as a primary efficacy variable, and complete the Oswestry Disability Index (ODI) and Patient's Global Impression of Change (PGIC) as secondary outcome measures. RESULTS: Out of 22 subjects that completed the study, 21 subjects (95%) reported improvements in average, best, and worst pain NPRS scores. All NPRS scores were significantly lower with subperception stimulation compared to paresthesia-based stimulation (p < 0.01, p < 0.05, and p < 0.05, respectively). As with NPRS scores, the treatment effect of subperception stimulation was significantly greater than that of paresthesia based stimulation on ODI scores (p = 3.9737 * 10-5 ) and PGIC scores (p = 3.0396 * 10-5 ). PMID- 27186824 TI - College Students' Drinking and Posting About Alcohol: Forwarding a Model of Motivations, Behaviors, and Consequences. AB - College drinking continues to remain a public health problem that has been exacerbated by alcohol-related posts on social networking sites (SNSs). Although existing research has linked alcohol consumption, alcohol posts, and adverse consequences to one another, comprehensive explanations for these associations have been largely unexplored. Thus, we reasoned that students' personal motivations (i.e., espousing an alcohol identity, needing entertainment, and adhering to social norms) influence their behaviors (i.e., alcohol consumption and alcohol-related posting on SNSs), which can lead to alcohol problems. Using structural equation modeling, we analyzed data from 364 undergraduate students and found general support for our model. In particular, espousing an alcohol identity predicted alcohol consumption and alcohol-related SNS posting, needing entertainment predicted alcohol consumption but not alcohol-related SNS posting, and adhering to social norms predicted alcohol-related SNS posting but not alcohol consumption. In turn, alcohol consumption and alcohol-related SNS posting predicted alcohol problems. It is surprising that alcohol-related SNS posting was a stronger predictor of alcohol problems than alcohol consumption. We discuss the findings within their applied applications for college student health. PMID- 27186823 TI - Neutrophil maturation rate determines the effects of dipeptidyl peptidase 1 inhibition on neutrophil serine protease activity. AB - BACKGROUND AND PURPOSE: Neutrophil serine proteases (NSPs) are activated by dipeptidyl peptidase 1 (DPP1) during neutrophil maturation. The effects of neutrophil turnover rate on NSP activity following DPP1 inhibition was studied in a rat pharmacokinetic/pharmacodynamic model. EXPERIMENTAL APPROACH: Rats were treated with a DPP1 inhibitor twice daily for up to 14 days; NSP activity was measured in onset or recovery studies, and an indirect response model was fitted to the data to estimate the turnover rate of the response. KEY RESULTS: Maximum NSP inhibition was achieved after 8 days of treatment and a reduction of around 75% NSP activity was achieved at 75% in vitro DPP1 inhibition. Both the rate of inhibition and recovery of NSP activity were consistent with a neutrophil turnover rate of between 4-6 days. Using human neutrophil turnover rate, it is predicted that maximum NSP inhibition following DPP1 inhibition takes around 20 days in human. CONCLUSIONS AND IMPLICATIONS: Following inhibition of DPP1 in the rat, the NSP activity was determined by the amount of DPP1 inhibition and the turnover of neutrophils and is thus supportive of the role of neutrophil maturation in the activation of NSPs. Clinical trials to monitor the effect of a DPP1 inhibitor on NSPs should take into account the delay in maximal response on the one hand as well as the potential delay in a return to baseline NSP levels following cessation of treatment. PMID- 27186825 TI - Open framework metal chalcogenides as efficient photocatalysts for reduction of CO2 into renewable hydrocarbon fuel. AB - Open framework metal chalcogenides are a family of porous semiconducting materials with diverse chemical compositions. Here we show that these materials containing covalent three-dimensional superlattices of nanosized supertetrahedral clusters can function as efficient photocatalysts for the reduction of CO2 to CH4. Unlike dense semiconductors, metal cations are successfully incorporated into the channels of the porous semiconducting materials to further tune the physical properties of the materials such as electrical conductivity and band gaps. In terms of the photocatalytic properties, the metal-incorporated porous chalcogenides demonstrated enhanced solar energy absorption and higher electrical conductivity and improved photocatalytic activity. PMID- 27186827 TI - Report from the 42(nd) congress of the Neurootological and Equilibriometric Society. PMID- 27186826 TI - Recurrence of Solid Pseudopapillary Neoplasms of the Pancreas: Results of a Nationwide Study of Risk Factors and Treatment Modalities. AB - BACKGROUND: Solid pseudopapillary neoplasms of the pancreas (SPPN) can relapse very late, but little is known about risk factors for recurrence and optimal treatment. We aimed to identify risk factors for recurrence and to analyze treatment modalities in all French pediatric cases of SPPN over the past 20 years. MATERIAL AND METHODS: Data were collected from pediatric oncologists and surgeons, and also from adult pancreatic surgeons in order to identify late recurrences. RESULTS: Fifty-one patients (41 girls) were identified. Median age at diagnosis was 13.1 years [8.7-17.9]. Abdominal pain was the commonest presenting symptom (32/49, 65%). The tumor was located in the pancreatic head in 24 patients (47%). Preoperative biopsy or cytology was performed in 14 cases (28%). All patients were operated with a median of 23 days [0-163] after diagnosis. The rate of postoperative morbidity was 29%. With a median follow-up of 65 months [0.3-221], the overall and event-free survival was 100% and 71%, respectively. Seven patients (13.7%) relapsed with a median of 43 months [33-94] after initial surgery. Six were treated surgically, either alone (n = 3) or with perioperative chemotherapy (n = 2) or hyperthermic intraperitoneal chemotherapy (n = 1). One patient in whom further treatment was not feasible was still alive at last news. Risk factors for recurrence were positive surgical margins (P = 0.03) and age less than 13.5 years at diagnosis (P = 0.03). CONCLUSIONS: SPPN recurrence in this pediatric series was a rare and late event that did not undermine overall survival. Complete surgical removal of recurrent tumors appears to be the best option. PMID- 27186828 TI - Usefulness of ultrasound-computer-craniocorpography in different vestibular disorders. AB - INTRODUCTION: Vertigo is one of the most unpleasant symptoms. Two of the main points of the examinations are the vestibulospinal tests (Romberg test and Unterberger- Fukuda test) can be measured objectively by the ultrasound-computer craniocorpography. OBJECTIVES: Using ultrasound-markers on head and shoulders, the ultrasound-computer-craniocorpography can measure and analyze the numerical data of statokinetic tests. The study is comparing the parameters of the vestibulospinal tests in different vestibular disorders. PATIENTS AND METHODS: 84 patients were examined. The main parameters in the standing test are the longitudinal and sway, the torticollis angle, and the forehead covering. In the stepping test the main parameters were the longitudinal deviation, the lateral sway, the angular deviation, and the self-spin degree. The patients were divided on normal, unilateral and bilateral peripheral lesion and central lesion groups. RESULTS: The data of the longitudinal and lateral sway and the forehead covering in Romberg test are quite different in the normal and dizzy patients. CONCLUSIONS: Ultrasound-computer-craniocorpography is a useful method in the examination of the balance system disorders. The differential diagnostic value is not sufficient alone, we needs other investigations for the topical diagnosis of the vestibular system. PMID- 27186829 TI - Electrophysiology quantitative electroencephalography/low resolution brain electromagnetic tomography functional brain imaging (QEEG LORETA): Case report: Subjective idiopathic tinnitus - predominantly central type severe disabling tinnitus. AB - The clinical significance of QEEG LORETA data analysis performed sequentially within 6 months is presented in a case report of a predominantly central type severe disabling subjective idiopathic tinnitus (SIT) before and following treatment. The QEEG LORETA data is reported as Z-scores of z = +/- 2.54, p < 0.013. The focus is on demonstration of patterns of brain wave oscillations reflecting multiple brain functions in multiple ROIs in the presence of the tinnitus signal (SIT). The patterns of brain activity both high, middle and low frequencies are hypothesized to reflect connectivities within and between multiple neuronal networks in brain. The Loreta source localization non auditory ROI Images at the maximal abnormality in the very narrow band frequency spectra (24.21 Hz), showed the mathematically most probable underlying sources of the scalp recorded data to be greatest in the mid-cingulate, bilateral precuneus, cingulate and the bilateral caudate nucleus. Clinical correlation of the data with the history and course of the SIT is considered an objective demonstration of the affect, behavioral, and emotional component of the SIT. The correlation of the caudate activity, SIT as the traumatic event with the clinical course of PTSD, and the clinical diagnosis of PTSD is discussed. The clinical translation for patient care is highlighted in a SIT patient with multiple comorbidities by translation of QEEG/LORETA electrophysiologic data, as an adjunct to: provide an objectivity of patterns of brain wave activity in multiple regions of interest (ROIs) reflecting multiple brain functions, in response to and in the presence of the tinnitus signal, recorded from the scalp and analyzed with the metrics of absolute power, relative power, asymmetry, and coherence, for the subjective tinnitus complaint (SIT); 2) provide an increase in the accuracy of the tinnitus diagnosis; 3) assess/monitor treatment efficacy; 4) provide a rationale for selection of a combined tinnitus targeted therapy of behavioral, pharmacologic, sound therapy modalities of treatment attempting tinnitus relief; 5) provide insight into the medical significance of the SIT; 6) attempt discriminant function analysis for identification of a particular diagnostic clinical category of CNS neuropsychiatric disease; and 7) attempt to translate what is known of the neuroscience of sensation, brain function, QEEG/LORETA source localization, for the etiology and prognosis of the individual SIT patient. PMID- 27186830 TI - The effect of tinnitus on some psychoacoustical abilities in individuals with normal hearing sensitivity. AB - INTRODUCTION: Tinnitus is the perception of a sound without an external source. It can affect auditory perception abilities in individuals with normal hearing sensitivity. PURPOSE: The aim of the study was to determine the effect of tinnitus on psychoacoustic abilities in individuals with normal hearing sensitivity. MATERIALS AND METHODS: The study was conducted on twenty subjects with tinnitus and twenty subjects without tinnitus. Tinnitus group was again divided into mild and moderate tinnitus based on the tinnitus handicap inventory. DATA COLLECTION AND ANALYSIS: Differential limen of intensity, differential limen of frequency, gap detection test, modulation detection thresholds were done through the mlp toolbox in Matlab and speech in noise test was done with the help of Quick SIN in Kannada. RESULTS: RESULTS of the study showed that the clinical group performed poorly in all the tests except for differential limen of intensity. CONCLUSIONS: Tinnitus affects aspects of auditory perception like temporal resolution, speech perception in noise and frequency discrimination in individuals with normal hearing. This could be due to subtle changes in the central auditory system which is not reflected in the pure tone audiogram. PMID- 27186831 TI - Development and standardization of Morningness-Eveningness Questionnaire (MEQ) in the Indian language Kannada. AB - INTRODUCTION: A circadian rhythm is any biological process that displays an endogenous, entrainable, oscillation of about 24 hours; the rhythms driven by a circadian clock and sleep have been widely observed in plants, animals, fungi and cyanobacteria. The main aim of the current study was to translate and validate the Morningness-Eveningness Questionnaire (MEQ) to Kannada (MEQ-K). MATERIALS AND METHODS: The English version of MEQ was translated to Kannada using translation back-translation method. Further it was given to 30 native Kannada speakers for content validation. The final MEQ-Kannada version was then administered on 93 normal native Kannada speakers. Statistical analysis was carried out using SPSS 17.0 software. Statistics such as mean, standard deviation and variance and reliability statistics such as Cronbach's alpha score as well as item-total correlation were obtained. RESULTS: RESULTS showed that, MEQ-K has a Cronbach's alpha score of 0.870 which is considered to be of good reliability. It was also observed that, even after deletion of any one item from the MEQ-K, the Cronbach's alpha score remained the same. CONCLUSION: From the current results it can be stated that, MEQ-K is a reliable tool that can categorize Kannada speaking population into various circadian types. PMID- 27186832 TI - The effect of circadian rhythm on the perceived tinnitus severity: A preliminary study. AB - INTRODUCTION: Hearing sound that does not originate in the world outside the body is an experience every human has at one time or another in life. Circadian rhythm is common for all living organisms and nearly all physiological functions, especially sleep-wake cycles, exhibit circadian rhythmicity. A short survey conducted in the study center revealed that majority of the tinnitus subjects reported a difference in tinnitus severity across the day. So the current study focused on finding out the influence of circadian rhythm on tinnitus severity. MATERIALS & METHODS: Study was conducted on 20 tinnitus subjects irrespective of age, gender, hearing status and type of tinnitus. Kannada version of MEQ was given to all the subjects to classify them to various circadian types. A visual analog scale was also given to rate the severity of the tinnitus in the morning and evening. RESULTS: The result of the current study states that, there was a significant difference in the tinnitus severity for moderate morning type individuals in the morning and evening and not for the intermediate group. CONCLUSION: So we can conclude that, circadian rhythm has a strong association with the severity of the tinnitus. PMID- 27186833 TI - Comparative analysis of vocabulary in children with cochlear implants. AB - INTRODUCTION: The use of tests assessing the speech of patients who underwent cochlear implant (CI) surgery is warranted to increase knowledge on the development of these patients' language skills. The ABFW Child Language Test evaluates vocabulary, phonology, fluency, and pragmatics and can be administered to these children. OBJECTIVE: To evaluate the vocabulary of children using CI. METHOD: This study included 16 children who underwent CI surgery between 1-4 years and 11 months old. Patients were divided into five groups according to age upon CI activation. RESULTS: In comparison with the age of brain's auditory development vs. chronological age of hearing children, all children using CI performed better. The comparison between children using unilateral CI and bilateral CI showed that those using bilateral CI had better results. When we compared children's performance considering the chronological age of deaf and hearing children, hearing children performed better. However, there were similar results when patients effectively used their CI and attended auditory rehabilitation sessions. CONCLUSION: In our study, the vocabulary of children using CI is similar to the vocabulary of hearing children. PMID- 27186834 TI - Diagnostic utility of Stenger test: reappraisal of its value. AB - OBJECTIVE: Nonorganic hearing loss (NOHL) is a lack of consistency in audiological testing. Although NOHL is relatively rare, it is important to identify suspicious patients. This study was designed to evaluate the effectiveness of Stenger test and acoustic reflexes test (ART) in the evaluation of patients with suspicious of unilateral NOHL. STUDY DESIGN: A prospective study Methods: In this study, 474 adult patients with suspicious unilateral profound or total hearing loss were included. Pure tone audiometry (PTA), speech audiometry, Stenger test, ART and click-evoked auditory brainstem response (ABR) measurements were performed. The sensitivity, specificity and predictive values of the Stenger test and ART for unilateral, profound to total NOHL were assessed by comparing these with the results of ABR. RESULTS: The sensitivity and specificity of the Stenger test in verifying unilateral, profound hearing loss were 99% and 57%, respectively. The positive and negative predictive values of the test were 88% and 97%, respectively. The sensitivity and specificity of the ART in verifying unilateral, profound hearing loss were 96% and 60% at 1000 Hz and 98% and 60% at 2000 Hz, respectively. The positive and negative predictive values of the ART were 50% and 97% at 1000 Hz, and 75% and 97% at 2000 Hz, respectively. CONCLUSION: The Stenger test and ART are widely used for the evaluation of unilateral or asymmetrical NOHL. In our opinion, these tests are significantly powerful. More difficult cases require ABR to verify nonorganic hearing loss and to exclude specific diagnoses that may imitate NOHL. PMID- 27186835 TI - Effectiveness of residual inhibition therapy. AB - INTRODUCTION: Tinnitus is considered as one of the major symptom associated with many pathologies along with its presence in individuals with normal hearing. With varied cause and mechanism of its generation and increase in number of individuals with complaint of tinnitus, rehabilitation becomes crucial for Audiologists. OBJECTIVE: Study was undertaken to find the efficacy of Residual Inhibition Therapy as treatment procedure for unilateral tinnitus in individuals with normal hearing by comparing pre and post Residual Inhibition Therapy, Contra lateral Acoustic Reflexes and Tinnitus Handicap Inventory. MATERIALS AND METHODS: Ten subjects between the age range of 20-45 years were included for the study. Tinnitus pitch and intensity were matched and Residual Inhibition Therapy was provided. The Pre Residual Inhibition Therapy, contra-lateral acoustic reflexes and Tinnitus Handicap Inventory scores were compared to post Residual Inhibition Therapy, contra-lateral acoustic reflexes and Tinnitus Handicap Inventory scores. RESULTS AND CONCLUSION: Statistical analysis revealed no significant difference, however, elevated contra-lateral acoustics reflexes post Residual Inhibition Therapy were seen. Even though small sample size made it hard to conclude on the effectiveness of Residual Inhibition Therapy as treatment of tinnitus, elevated contralateral acoustic reflexes post Residual Inhibition Therapy pay way for further advanced studies on the same. PMID- 27186836 TI - Prevalence of hearing loss in newborns of mothers who had malaria and were treated with antimalaric drugs in pregnancy. AB - INTRODUCTION: Gestational malaria is related to very bad perinatal outcomes and antimalarial drugs used during pregnancy can be ototoxic to the fetus. OBJECTIVE: To determine the prevalence of hearing loss in newborns of mothers who had malaria and treated with antimalarial drugs during pregnancy. MATERIALS AND METHODS: Cross-sectional study which involved 35 newborns. All underwent neonatal hearing screening with otoacoustic emissions combined with automatic auditory brainstem response. Those who failed were referred to audiological diagnosis with evoked otoacoustic emissions and brainstem auditory evoked potential associated with tympanometry (1000 Hz). Data were obtained through interviews with the mothers' and analyzing the patient chart and the newborn, and underwent to statistical tests analysis of variance, equality of two proportions and Chi square test (p = 0.05). RESULTS: The infection by Plasmodium vivax and chloroquine treatment with the first quarter prevailed; 88.6% (n = 31) newborns passed the hearing screening and 11.4% (n = 4) failed, of these, 50% (n = 2) attended for diagnosis, being diagnosed with hearing loss. CONCLUSION: The prevalence of hearing loss in newborns of mothers who had vivax malaria and used chloroquine during pregnancy was 3%. PMID- 27186837 TI - Caffeine effect in vestibular system. AB - INTRODUCTION: Caffeine benefits and harms in health is a very controversial subject for a scientific research. METHODS: This is a systematic literature using PubMed database linking caffeine with the following keywords: 'vestibular', 'vertigo', 'vestibular function', 'caloric tests' e 'electronystagmography". RESULTS: Thirty articles were found and ten were analyzed for fulfill the inclusion criteria. These ten articles were grouped and then a separated in four groups, according to the approach. CONCLUSION: There is a need of further randomized and controlled studies to understand the vestibular system. PMID- 27186838 TI - Vestibular evoked myogenic potential: its use in Sudden Sensorineural Hearing Loss. AB - INTRODUCTION: Sudden sensorineural hearing loss (SHL) has uncertain origin and evolution. Vestibular evoked myogenic potential (VEMP) estimates of the vestibular pathway that can not be analyzed by the other entrance examinations, which can be helpful in diagnosing the extent of hearing damage in these patients. OBJECTIVES: To investigate the clinical applicability of VEMP in patients with SHL. METHODS: This is a systematic review. Searches were conducted in the databases PubMed/Medline, SciELO and LILACS. Data were tabulated. RESULTS: We found 45 articles, 15 of these made up the study by fitting either the inclusion factors. The objective of 60% of the studies was to determine whether the VEMP can be used as predictive hearing recovery Conclusion: VEMP may be useful as hearing recovery predictor in patients with sudden sensorineural hearing loss, justifying the implementation of such examination in this population. PMID- 27186839 TI - Hyperproduction of gamma-glutamyl transpeptidase from Bacillus licheniformis ER15 in the presence of high salt concentration. AB - BACKGROUND: Microbial gamma-glutamyl transpeptidases (GGTs) have been exploited in biotechnological, pharmaceutical, and food sectors for the synthesis of various gamma-glutamyl compounds. But, till date, no bacterial GGTs are commercially available in the market because of lower levels of production from various sources. In the current study, production of GGT from Bacillus licheniformis ER15 was investigated to achieve high GGT titers. RESULTS: Hyperproduction of GGT from B. licheniformis ER15 was achieved with 6.4-fold enhancement (7921.2 +/- 198.7 U/L) by optimization of culture medium following one-variable-at-a-time strategy and statistical approaches. Medium consisting of Na2HPO4: 0.32% (w/v); KH2PO4: 0.15% (w/v); starch: 0.1% (w/v); soybean meal: 0.5% (w/v); NaCl: 4.0% (w/v), and MgCl2: 5 mM was found to be optimal for maximum GGT titers. Maximum GGT titers were obtained, in the optimized medium at 37 degrees C and 200 rpm, after 40 h. It was noteworthy that GGT production was a linear function of sodium chloride concentration, as observed during response surface methodology. While investigating the role of NaCl on GGT production, it was found that NaCl drastically decreased subtilisin concentration and indirectly increasing GGT recovery. CONCLUSION: B. licheniformis ER15 is proved to be a potential candidate for large-scale production of GGT enzyme and its commercialization. PMID- 27186844 TI - Chemical-Bonding-Directed Hierarchical Assembly of Nanoribbon-Shaped Nanocomposites of Gold Nanorods and Poly(3-hexylthiophene). AB - Nanoribbon-shaped nanocomposites composed of conjugated polymer poly(3 hexylthiophene) (P3HT) nanoribbons and plasmonic gold nanorods (AuNRs) were crafted by a co-assembly of thiol-terminated P3HT (P3HT-SH) nanofibers with dodecanethiol-coated AuNRs (AuNRs-DDT). First, P3HT-SH nanofibers were formed due to interchain pi-pi stacking. Upon the addition of AuNRs-DDT, P3HT-SH nanofibers were transformed into nanoribbons decorated with the aligned AuNRs on the surface (i.e., nanoribbon-like P3HT/AuNRs nanocomposites). Depending on the surface coverage of the P3HT nanoribbons by AuNRs, these hierarchically assembled nanocomposites exhibited broadened and red-shifted absorption bands of AuNRs in nIR region due to the plasmon coupling of adjacent aligned AuNRs and displayed quenched photoluminescence of P3HT. Such conjugated polymer/plasmonic nanorod nanocomposites may find applications in fields, such as building blocks for complex superstructures, optical biosensors, and optoelectronic devices. PMID- 27186840 TI - Microbial Community Metabolic Modeling: A Community Data-Driven Network Reconstruction. AB - Metabolic network modeling of microbial communities provides an in-depth understanding of community-wide metabolic and regulatory processes. Compared to single organism analyses, community metabolic network modeling is more complex because it needs to account for interspecies interactions. To date, most approaches focus on reconstruction of high-quality individual networks so that, when combined, they can predict community behaviors as a result of interspecies interactions. However, this conventional method becomes ineffective for communities whose members are not well characterized and cannot be experimentally interrogated in isolation. Here, we tested a new approach that uses community level data as a critical input for the network reconstruction process. This method focuses on directly predicting interspecies metabolic interactions in a community, when axenic information is insufficient. We validated our method through the case study of a bacterial photoautotroph-heterotroph consortium that was used to provide data needed for a community-level metabolic network reconstruction. Resulting simulations provided experimentally validated predictions of how a photoautotrophic cyanobacterium supports the growth of an obligate heterotrophic species by providing organic carbon and nitrogen sources. J. Cell. Physiol. 231: 2339-2345, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27186845 TI - T2* Measurement bias due to concomitant gradient fields. AB - PURPOSE: To demonstrate that concomitant magnetic fields can cause significant spatially dependent biases in T2* relaxometry measurements with implications for clinical applications such as BOLD and dynamic susceptibility contrast-enhanced MRI. THEORY AND METHODS: After developing a theoretical framework for intravoxel dephasing and signal loss from concomitant magnetic fields, this framework and the effect of concomitant fields on T2* are validated with phantom experiments and numerical simulation. In lower leg and renal T2* mapping, we quantify measurement bias for imaging protocols with high gradient amplitude multiecho readouts, comparable to those used in clinical applications. RESULTS: Concordance between phantom experiment and numerical simulation validate the theoretical framework. Changes in T2* measured in the lower leg and kidney varied by up to 15% and 35%, respectively, as a result of concomitant gradient effects when compared with the control measurements. CONCLUSION: Concomitant magnetic fields produced by imaging gradient coils can cause clinically significant T2* mapping errors when high amplitude, long duration gradient waveforms are used. While we have shown that measurement biases can be quite large, modification of imaging parameters can potentially reduce concomitant field-induced measurement errors to acceptable levels. Magn Reson Med 77:1562-1572, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 27186846 TI - Bone engineering in dog mandible: Coculturing mesenchymal stem cells with endothelial progenitor cells in a composite scaffold containing vascular endothelial growth factor. AB - We sought to assess the effects of coculturing mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) in the repair of dog mandible bone defects. The cells were delivered in beta-tricalcium phosphate scaffolds coated with poly lactic co-glycolic acid microspheres that gradually release vascular endothelial growth factor (VEGF). The complete scaffold and five partial scaffolds were implanted in bilateral mandibular body defects in eight beagles. The scaffolds were examined histologically and morphometrically 8 weeks after implantation. Histologic staining of the decalcified scaffolds demonstrated that bone formation was greatest in the VEGF/MSC scaffold (63.42 +/- 1.67), followed by the VEGF/MSC/EPC (47.8 +/- 1.87) and MSC/EPC (45.21 +/- 1.6) scaffolds, the MSC scaffold (34.59 +/- 1.49), the VEGF scaffold (20.03 +/- 1.29), and the untreated scaffold (7.24 +/- 0.08). Hence, the rate of new bone regeneration was highest in scaffolds containing MSC, either mixed with EPC or incorporating VEGF. Adding both EPC and VEGF with the MSC was not necessary. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1767-1777, 2017. PMID- 27186847 TI - Disrupted trabecular bone micro-architecture in middle-aged male HIV-infected treated patients. AB - OBJECTIVES: HIV-infected individuals are at increased risk of incident fractures. Evaluation of trabecular bone micro-architecture is an important tool to assess bone strength, but its use has not yet been reported in middle-aged HIV-infected male individuals. The aim of the study was to compare bone micro-architecture between HIV-infected and HIV-uninfected men. METHODS: In this cross-sectional study, 53 HIV-infected male individuals with a mean (+/- standard deviation) age of 49 +/- 9 years who had been receiving antiretroviral therapy including tenofovir disoproxil fumarate (DF) for at least 60 months were compared with 50 HIV-uninfected male controls, matched for age and ethnic origin. We studied the volumetric bone density and micro-architecture of the radius and tibia using high resolution peripheral quantitative computed tomography (HR-p QCT). RESULTS: Volumetric trabecular bone density was 17% lower in the tibia (P < 10(-4) ) and 16% lower in the radius (P < 10(-3) ) in HIV-infected patients compared with controls. By contrast, the cortical bone density was normal at both sites. The tibial trabecular micro-architecture differed markedly between patients and controls: bone volume/total volume (BV/TV) and trabecular number were each 13% lower (P < 10(-4) for both). Trabecular separation and inhomogeneity of the network were 18% and 24% higher in HIV-infected patients than in controls, respectively. The radial BV/TV and trabecular thickness were each 13% lower (P < 10(-3) and 10(-2) , respectively). Cortical thickness was not different between the two groups. CONCLUSIONS: The findings of lower volumetric trabecular bone density and disrupted trabecular micro-architectural parameters in middle-aged male HIV-infected treated patients help to explain bone frailty in these patients. PMID- 27186848 TI - Intuition: A Concept Analysis. AB - PURPOSE: The purpose of this article is to conceptually examine intuition; identify the importance of intuition in nursing education, clinical practice, and patient care; encourage acceptance of the use of intuition; and add to the body of nursing knowledge. BACKGROUND: Nurses often report using intuition when making clinical decisions. Intuition is a rapid, unconscious process based in global knowledge that views the patient holistically while synthesizing information to improve patient outcomes. However, with the advent of evidence-based practice (EBP), the use of intuition has become undervalued in nursing. REVIEW METHODS: Walker and Avant's framework was used to analyze intuition. A literature search from 1987 to 2014 was conducted using the following keywords: intuition, intuition and nursing, clinical decision making, clinical decision making and intuition, patient outcomes, EBP, and analytical thinking. RESULTS: The use of intuition is reported by nurses, but is not legitimized within the nursing profession. Defining attributes of intuition are an unconscious, holistic knowledge gathered without using an analytical process and knowledge derived through synthesis, not analysis. Consequences include verification of intuition through an analytical process and translating that knowledge into a course of action. CONCLUSION: This article supports the use of intuition in nursing by offering clarity to the concept, adds to the nursing knowledge base, encourages a holistic view of the patient during clinical decision making, and encourages nurse educators to promote the use of intuition. PMID- 27186849 TI - Stereotactic radiosurgery for intracranial metastases: linac-based and gamma dedicated unit approach. AB - INTRODUCTION: For intracranial metastases, the role of stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy is well recognized. AREAS COVERED: Historically, the first technology, for stereotactic device able to irradiate a brain tumor volume, was Gamma Knife(r) (GK). Due to the technological advancement of linear accelerator (Linac), there was a continuous increasing interest in SRS Linac-based applications. In those decades, it was assumed a superiority of GK compared to SRS Linac-based for brain tumor in terms of dose conformity and rapid fall-off dose close to the target. Expert commentary: Recently, due to the Linac technologic advancement, the choice of SRS GK-based is not necessarily so exclusive. The current review discussed in details the technical and clinical aspects comparing the two approaches for brain metastases. PMID- 27186850 TI - Demonstration of Trophozoites of G. Lamblia in Ileal Mucosal Biopsy Specimens May Reveal Giardiasis in Patients With Significantly Inflamed Parasite-free Duodenal Mucosa. AB - In the majority of individuals, infestation with trophozoites of Giardia lamblia (synonymous G. duodenalis or G. intestinalis) leads to a self-limited disease. Whereas most duodenal biopsies with chronic giardiasis show little or no inflammatory reaction, some patients may develop a severe disease with significant mucosal inflammation and various degrees of villous blunting. Occasionally, the histologic changes may resemble those of celiac disease. In this paper, we describe 11 patients, 5 of them female, with chronic giardiasis and demonstrable G. lamblia in ileal biopsies. The median age was 45 years (35 to 62 y), with male patients being at least 10 years younger than female patients. All of the duodenal biopsies showed at least mild villous blunting (grading: mild, marked, or total). In the mucosa an increased number of plasma cells and lymphocytes was observed. Furthermore, varying numbers of granulocytes were found in the lamina propria and in the epithelial layer. In 1 case only, the number of intraepithelial lymphocytes was >40/100 epithelial cells thus mirroring the histologic picture of celiac disease with a flat mucosa (with negative celiac disease-specific serological findings). Interestingly enough, all mucosal biopsy specimens from the duodenum were parasite free. Therefore, giardiasis could only be revealed by the demonstration of trophozoites of G. lamblia in biopsy specimens from the terminal ileum, which had been taken simultaneously or several weeks later. In contrast to duodenal biopsies, the ileal mucosa appeared either normal or only mildly inflamed in this setting. All patients but 1 were symptomatic, with chronic diarrhea being the leading symptom. Symptoms resolved after antibiotic therapy. This study demonstrates that giardiasis may be associated with a significant duodenal pathology in biopsy specimens without discernible parasites. In the cases described here infestation with G. lamblia was only proven histologically by examination of mucosal biopsy specimens taken from the terminal ileum. PMID- 27186852 TI - Anatomic Invasive Depth Predicts Delayed Cervical Lymph Node Metastasis of Tongue Squamous Cell Carcinoma. AB - Delayed cervical lymph node metastasis (CLNM) is the most negative prognostic factor of tongue squamous cell carcinoma (SCC). This study analyzed the relationship between clinicopathologic factors, including anatomic invasive depth (AID), and CLNM. A total of 212 patients with clinically node-negative (cN0) tongue SCC who had undergone partial glossectomy through the mouth were eligible for this retrospective study. The deepest portions where tongue SCC cells invaded as determined by microscopic analyses were classified into 5 categories, including epithelial and submucosal tissue, lateral extrinsic tongue muscle (ETM), intrinsic tongue muscles (ITM), paralingual and sublingual spaces, and medial ETM according to AID. We examined the relationship between clinicopathologic factors including AID and delayed CLNM. Multivariate analysis demonstrated that AID was an independent predictive factor for delayed CLNM (P=0.0022; odds ratio=7.1). Deeper invasion than ITM, including ITM, paralingual and sublingual spaces, and medial ETM, had high sensitivity and negative predictive value for delayed CLNM (94.4% and 95.7%, respectively). Precise elucidation of AID may be useful for the preoperative decision for performing elective neck dissection. None of 11 patients in whom the deepest portion where tumor invaded to lateral ETM (according to AID) showed delayed CLNM, although tongue SCC T4a tumor is defined by the presence of invasion of cancer cells to ETM. Tumors with invasion to lateral ETM might have to be excluded from the pathologic T4a category. PMID- 27186853 TI - Unusual Mismatch Repair Immunohistochemical Patterns in Endometrial Carcinoma. AB - Universal screening for Lynch syndrome through mismatch repair (MMR) immunohistochemistry (IHC) on tumor samples has brought to light several heterogenous MMR staining patterns. At our institution, a prospective study of universal Lynch syndrome screening using MMR IHC on 125 endometrial cancers (EC) led to the identification of subclonal loss of MMR protein expression within the tumor (n=9). We also interrogated the MMR staining patterns in MMR-deficient EC with concurrent endometrial intraepithelial neoplasia (EIN; n=14) and all mixed type ECs (n=14) to look for concordant or discordant profiles between the various components. MLH1 promoter methylation and microsatellite instability testing was performed on discordant subclones. Abrupt and complete subclonal loss of MMR expression was identified in 9 cases (7.2%; 7 subclonal MLH1/PMS2 loss, 1 subclonal loss of MLH1 and complete loss of PMS2, and 1 subclonal MSH6 loss). All subclonal MLH1 losses were associated with epigenetic silencing. In cases with concomitant EIN (n=14), 7 cases showed concordant MMR IHC between EC and EIN, and 4 cases showed MMR protein loss confined to the EC. The remaining 3 cases demonstrated subclonal staining in the EIN. In mixed tumors (n=14), subclonal or total MMR IHC deficiency was confined to endometrioid components. In summary, discrete subclonal loss of MMR protein expression occurs in up to 7.2% of EC and, in our experience, only in endometrioid components. Importantly, subclonal MLH1 MMR defects appear to be a biological phenomenon that can be explained by methylation and somatic events, without evidence of underlying germline alterations. PMID- 27186851 TI - Assessing p16 Status of Oropharyngeal Squamous Cell Carcinoma by Combined Assessment of the Number of Cells Stained and the Confluence of p16 Staining: A Validation by Clinical Outcomes. AB - Human papillomavirus-related oropharyngeal squamous cell carcinoma (OPSCC) has favorable prognosis relative to other head and neck squamous cell carcinomas. Criteria for predicting human papillomavirus status based upon p16 staining, including difficult cases with partial staining patterns, have been developed; however, clinical validation of these criteria and the clinical significance of partial p16 staining have not been reported. Eighty-one archival OPSCC cases were initially stained for p16 by immunohistochemistry with clone G175-405. The percentage of p16 cells and percentage of confluence of p16 cells were categorized as 25%, 26% to 75%, or >75%. Of all cases, 16 (20%) had partial p16 expression, with 26% to 75% p16 cells. Applying previously developed criteria of >75% p16 cells or >50% positive cells with >25% confluence, 48 (59%) patients were categorized p16 and demonstrated expected clinical characteristics and superior disease-free survival and overall survival (P<0.001) compared with p16 patients. By themselves, the partial staining patients had intermediate outcomes; however, separating the partial staining cases by degree of confluence showed that those with >75% confluence had superior disease-free survival (P=0.042). When the 16 original partial staining cases were re-stained with the alternative anti-p16 E6H4 clone, p16 status remained concordant for all cases, but only 3 of the 16 were interpreted as demonstrating partial staining. This report shows that the prevalence of partial p16 staining varies with the antibody utilized and clinically validates the application of a graded evaluation of both the number as well as confluence of positive cells for risk stratification of patients with OPSCC. PMID- 27186854 TI - INTERFACING INFANT MENTAL HEALTH KNOWLEDGE SYSTEMS: REFLECTIONS ON THE NARRATIVES OF LAY HOME VISITORS' EXPERIENCES OF LEARNING AND APPLYING RELATIONAL CONCEPTS OF DEVELOPMENT IN A SOUTH AFRICAN INTERVENTION PROGRAM. AB - The question of interfacing research and clinically generated knowledge in the field of infant mental health (IMH) with local cultural knowledge and belief systems has provoked extended discussion in recent years. This article explores convergences and divergences between current research-based, relational IMH mental health models and "community" knowledge held by a group of South African lay home visitors from a socioeconomically deprived township. These women were trained in a psychoanalytic and attachment-informed infant mental health program that promotes a relational model of infant development. They provide an intervention that supports high risk mother-infant relationships in the same locality. A two-tiered approach was taken to the analysis of the home visitor interviews and focused on the home visitors' constructed narratives of infant development posttraining as well as the personal impact of the training and work on the home visitors themselves. The study found that psychoanalytic and attachment-informed thinking about development makes sense to those operating within the local South African cultural context, but that the accommodation of this knowledge is a complex and challenging process. PMID- 27186855 TI - Subtle Interplay between Localized Magnetic Moments and Itinerant Electrons in LaAlO3/SrTiO3 Heterostructures. AB - Clarification of the role of magnetic ordering and scattering in two-dimensional electron gas has become increasingly important to understand the transport and magnetic behavior in the LaAlO3 (LAO)/SrTiO3 (STO) heterostructures. In this work, we report the sheet resistance of the LAO/STO heterostructures as functions of temperature, magnetic field, and field orientation. An unexpected resistance minimum was discovered at ~10 K under a sufficiently high in-plane magnetic field. An anisotropic magnetoresistance (MR) is clearly identified, indicating the presence of magnetic scattering which may be related to the interaction between itinerant electrons and localized magnetic moments in the LaAlO3/SrTiO3 heterostructures. It is believed that the high concentration of oxygen vacancies induced by the ultralow oxygen partial pressure during the deposition process plays a predominant role in the occurrence of the anisotropic MR. PMID- 27186857 TI - Factors limiting romantic relationship formation for individuals with early psychosis. AB - BACKGROUND: Although many young adults with early psychosis (EP) desire to engage in a romantic relationship, many report having difficulties in engaging in such a relationship. However, almost no research has been conducted on factors potentially explaining impairments in their ability to form romantic relationships. AIM: To compare an EP single young adult sample with single students or students in stable romantic relationships on factors that can cause difficulties in romantic relationship initiation processes METHODS: Cross sectional study comparing these three groups (n = 83) on self-esteem, attachment, social functioning and perceived difficulties in dating. RESULTS: No significant group differences were found on self-esteem, although lack of confidence was the second most frequent reason evoked by EP participants when asked why they were single. EP participants had greater attachment preoccupation than students involved in a relationship. Single EP individuals rated their social interaction abilities higher compared with single students, but did not engage in social interactions more often. Both single EP participants and single students had more negative perceptions of their intimacy abilities and fewer intimacy behaviours compared with participants involved in a relationship. CONCLUSIONS: Potential interventions to improve EP young adult's capacity to engage in romantic relationships could target perception of their interaction skills, preoccupation about being loved, negative perception of their intimacy abilities, frequency of intimacy related behaviours and lack of confidence. PMID- 27186856 TI - Visible-Light-Induced Olefin Activation Using 3D Aromatic Boron-Rich Cluster Photooxidants. AB - We report a discovery that perfunctionalized icosahedral dodecaborate clusters of the type B12(OCH2Ar)12 (Ar = Ph or C6F5) can undergo photo-excitation with visible light, leading to a new class of metal-free photooxidants. Excitation in these species occurs as a result of the charge transfer between low-lying orbitals located on the benzyl substituents and an unoccupied orbital delocalized throughout the boron cluster core. Here we show how these species, photo-excited with a benchtop blue LED source, can exhibit excited-state reduction potentials as high as 3 V and can participate in electron-transfer processes with a broad range of styrene monomers, initiating their polymerization. Initiation is observed in cases of both electron-rich and electron-deficient styrene monomers at cluster loadings as low as 0.005 mol%. Furthermore, photo-excitation of B12(OCH2C6F5)12 in the presence of a less activated olefin such as isobutylene results in the production of highly branched poly(isobutylene). This work introduces a new class of air-stable, metal-free photo-redox reagents capable of mediating chemical transformations. PMID- 27186858 TI - Association Between HbA1c Variability and Risk of Microvascular Complications in Adolescents With Type 1 Diabetes. AB - CONTEXT: There is a paucity of data regarding the association between glycosylated hemoglobin (HbA1c) variability and risk of microvascular complications in adolescents with type 1 diabetes (T1D). OBJECTIVE: To investigate the association between HbA1c variability and risk of microvascular complications in adolescents with T1D. DESIGN: Prospective cohort study from 1990 to 2014 (median follow-up, 8.1 y). SETTING: Tertiary pediatric hospital. PARTICIPANTS: A total of 1706 adolescents (aged 12-20 minimum diabetes duration 5 y) with median age of 15.9 years (interquartile range, 14.3-17.5) and diabetes duration of 8.1 years (6.3-10.8). MAIN OUTCOME MEASURES: Glycemic variability was computed as the SD of all HbA1c measurements (SD-HbA1c) after diagnosis. Retinopathy was detected using 7-field fundal photography, renal function assessed using albumin excretion rate, peripheral neuropathy detected using thermal and vibration threshold testing, and cardiac autonomic neuropathy (CAN) detected using time- and frequency-domain analyses of electrocardiogram recordings. Generalized estimating equations were used to examine the relationship between complications outcomes and HbA1c variability, after adjusting for known risk factors, including HbA1c, diabetes duration, blood pressure, and lipids. RESULTS: In multivariable analysis, SD-HbA1c was associated with early retinopathy (odds ratio [OR] 1.32; 95% confidence interval, 1.00 1.73), albuminuria (OR 1.81; 1.04-3.14), increased log10 albumin excretion rate (OR 1.10; 1.05-1.15) and CAN (OR 2.28; 1.23-4.21) but not peripheral neuropathy. CONCLUSIONS: Greater HbA1c variability predicts retinopathy, early nephropathy, and CAN, in addition to established risk factors, in adolescents with T1D. Minimizing long term fluctuations in glycemia may provide additional protection against the development of microvascular complications. PMID- 27186860 TI - Risk Stratification of Neck Lesions Detected Sonographically During the Follow-Up of Differentiated Thyroid Cancer. AB - CONTEXT: The European Thyroid Association (ETA) has classified posttreatment cervical ultrasound findings in thyroid cancer patients based on their association with disease persistence/recurrence. OBJECTIVE: The objective of the study was to assess this classification's ability to predict the growth and persistence of such lesions during active posttreatment surveillance of patients with differentiated thyroid cancer (DTC). DESIGN: This was a retrospective, observational study. SETTING: The study was conducted at a thyroid cancer center in a large Italian teaching hospital. PATIENTS: Center referrals (2005-2014) were reviewed and patients selected with pathologically-confirmed DTC; total thyroidectomy, with or without neck dissection and/or radioiodine remnant ablation; abnormal findings on two or more consecutive posttreatment neck sonograms; and subsequent follow-up consisting of active surveillance. Baseline ultrasound abnormalities (thyroid bed masses, lymph nodes) were classified according to the ETA system. Patients were divided into group S (those with one or more lesions classified as suspicious) and group I (indeterminate lesions only). We recorded baseline and follow-up clinical data through June 30, 2015. MAIN OUTCOMES: The main outcomes were patients with growth (>3 mm, largest diameter) of one or more lesions during follow-up and patients with one or more persistent lesions at the final visit. RESULTS: The cohort included 58 of the 637 DTC cases screened (9%). A total of 113 lesions were followed up (18 thyroid bed masses, 95 lymph nodes). During surveillance (median 3.7 y), group I had significantly lower rates than group S of lesion growth (8% vs 36%, P = .01) and persistence (64% vs 97%, P = .014). The median time to scan normalization was 2.9 years. CONCLUSIONS: The ETA's evidence-based classification of sonographically detected neck abnormalities can help identify papillary thyroid cancer patients eligible for more relaxed follow-up. PMID- 27186861 TI - Epidemiology and Health-Related Quality of Life in Hypoparathyroidism in Norway. AB - OBJECTIVE: The epidemiology of hypoparathyroidism (HP) is largely unknown. We aimed to determine prevalence, etiologies, health related quality of life (HRQOL) and treatment pattern of HP. METHODS: Patients with HP and 22q11 deletion syndrome (DiGeorge syndrome) were identified in electronic hospital registries. All identified patients were invited to participate in a survey. Among patients who responded, HRQOL was determined by Short Form 36 and Hospital Anxiety and Depression scale. Autoantibodies were measured and candidate genes (CaSR, AIRE, GATA3, and 22q11-deletion) were sequenced for classification of etiology. RESULTS: We identified 522 patients (511 alive) and estimated overall prevalence at 102 per million divided among postsurgical HP (64 per million), nonsurgical HP (30 per million), and pseudo-HP (8 per million). Nonsurgical HP comprised autosomal dominant hypocalcemia (21%), autoimmune polyendocrine syndrome type 1 (17%), DiGeorge/22q11 deletion syndrome (15%), idiopathic HP (44%), and others (4%). Among the 283 respondents (median age, 53 years [range, 9-89], 75% females), seven formerly classified as idiopathic were reclassified after genetic and immunological analyses, whereas 26 (37% of nonsurgical HP) remained idiopathic. Most were treated with vitamin D (94%) and calcium (70%), and 10 received PTH. HP patients scored significantly worse than the normative population on Short Form 36 and Hospital Anxiety and Depression scale; patients with postsurgical scored worse than those with nonsurgical HP and pseudo-HP, especially on physical health. CONCLUSIONS: We found higher prevalence of nonsurgical HP in Norway than reported elsewhere. Genetic testing and autoimmunity screening of idiopathic HP identified a specific cause in 21%. Further research is necessary to unravel the causes of idiopathic HP and to improve the reduced HRQOL reported by HP patients. PMID- 27186863 TI - Reply. PMID- 27186859 TI - Vitamin D Status Relates to Reproductive Outcome in Women With Polycystic Ovary Syndrome: Secondary Analysis of a Multicenter Randomized Controlled Trial. AB - CONTEXT: Experimental evidence supports a relevance of vitamin D (VitD) for reproduction; however, data in humans are sparse and inconsistent. OBJECTIVE: To assess the relationship of VitD status with ovulation induction (OI) outcomes in women with polycystic ovary syndrome (PCOS). DESIGN: A retrospective cohort. SETTING: Secondary analysis of randomized controlled trial data. PARTICIPANTS: Participants in the Pregnancy in PCOS I (PPCOS I) randomized controlled trial (n = 540) met the National Institutes of Health diagnostic criteria for PCOS. INTERVENTIONS: Serum 25OHD levels were measured in stored sera. MAIN OUTCOME MEASURES: Primary, live birth (LB); secondary, ovulation and pregnancy loss after OI. RESULTS: Likelihood for LB was reduced by 44% for women if the 25OHD level was < 30 ng/mL (<75 nmol/L; odds ratio [OR], 0.58 [0.35-0.92]). Progressive improvement in the odds for LB was noted at thresholds of >=38 ng/mL (>=95 nmol/L; OR, 1.42 [1.08-1.8]), >=40 ng/mL (>=100 nmol/L; OR, 1.51 [1.05-2.17]), and >=45 ng/mL (>=112.5 nmol/L; OR, 4.46 [1.27-15.72]). On adjusted analyses, VitD status was an independent predictor of LB and ovulation after OI. CONCLUSIONS: In women with PCOS, serum 25OHD was an independent predictor of measures of reproductive success after OI. Our data identify reproductive thresholds for serum 25OHD that are higher than recommended for the nonpregnant population. PMID- 27186862 TI - Microcystin-LR induces mitotic spindle assembly disorders in Vicia faba by protein phosphatase inhibition and not reactive oxygen species induction. AB - We aimed to reveal the mechanisms of mitotic spindle anomalies induced by microcystin-LR (MCY-LR), a cyanobacterial toxin in Vicia faba, a well-known model in plant cell and molecular biology. MCY-LR inhibits type 1 and 2A phosphoserine/threonine specific protein phosphatases (PP1 and PP2A) and induces reactive oxygen species (ROS) formation. The cytoskeleton is one of the main targets of the cyanotoxin during cytopathogenesis. Histochemical immunohistochemical and biochemical methods were used. A significant number of MCY-LR induced spindle alterations are described for the first time. Disrupted, multipolar spindles and missing kinetochore fibers were detected both in metaphase and anaphase cells. Additional polar microtubule (MT) bundles, hyperbundling of spindle MTs, monopolar spindles, C-S- shaped, additional and asymmetric spindles were detected in metaphase, while midplane kinetochore fibers were detected in anaphase cells only. Several spindle anomalies induced mitotic disorders, i.e. they occurred concomitantly with altered sister chromatid separation. Alterations were dependent on the MCY-LR dose and exposure time. Under long-term (2 and mainly 6 days') exposure they were detected in the concentration range of 0.1-20MUgmL(-1) MCY-LR that inhibited PP1 and PP2A significantly without significant ROS induction. Elevated peroxidase/catalase activities indicated that MCY-LR treated V. faba plants showed efficient defense against oxidative stress. Thus, although the elevation of ROS is known to induce cytoskeletal aberrations in general, this study shows that long-term protein phosphatase inhibition is the primary cause of MCY-LR induced spindle disorders. PMID- 27186864 TI - Dynamics of the Chiral Liquid Crystal 4'-Butyl-4-(S)-(2-methylbutoxy)azoxybenzene in the Isotropic, Cholesteric, and Solid Phases: A Fast Field-Cycling NMR Relaxometry Study. AB - (1)H NMR relaxometry was applied to investigate dynamic processes in the isotropic liquid, cholesteric, and crystalline phases of the chiral mesogen 4' butyl-4-(S)-(2-methylbutoxy)azoxybenzene (4ABO5*). To this aim, (1)H longitudinal relaxation rates were measured as a function of temperature (between 257 and 319 K) and Larmor frequency (from 10 kHz to 35 MHz by a fast field-cycling relaxometer and at 400 MHz by an NMR spectrometer). The NMR relaxation dispersion (NMRD) curves so obtained were analyzed in terms of models suitable for the description of dynamic processes in the different phases, thus quantitatively determining values of characteristic motional parameters. In particular, internal and overall rotations/reorientations, molecular translational diffusion, and collective motions contribute to relaxation in the isotropic and cholesteric phases, whereas, in the crystalline phase, relaxation is mainly determined by internal motions and molecular reorientations. The results were discussed and compared with those previously obtained on the same compound by dielectric relaxation spectroscopy. PMID- 27186865 TI - Quantifying the changes in survival inequality for Indigenous people diagnosed with cancer in Queensland, Australia. AB - The survival inequality faced by Indigenous Australians after a cancer diagnosis is well documented; what is less understood is whether this inequality has changed over time and what this means in terms of the impact a cancer diagnosis has on Indigenous people. Survival information for all patients identified as either Indigenous (n=3168) or non-Indigenous (n=211,615) and diagnosed in Queensland between 1997 and 2012 were obtained from the Queensland Cancer Registry, with mortality followed up to 31st December, 2013. Flexible parametric survival models were used to quantify changes in the cause-specific survival inequalities and the number of lives that might be saved if these inequalities were removed. Among Indigenous cancer patients, the 5-year cause-specific survival (adjusted by age, sex and broad cancer type) increased from 52.9% in 1997-2006 to 58.6% in 2007-2012, while it improved from 61.0% to 64.9% among non Indigenous patients. This meant that the adjusted 5-year comparative survival ratio (Indigenous: non-Indigenous) increased from 0.87 [0.83-0.88] to 0.89 [0.87 0.93], with similar improvements in the 1-year comparative survival. Using a simulated cohort corresponding to the number and age-distribution of Indigenous people diagnosed with cancer in Queensland each year (n=300), based on the 1997 2006 cohort mortality rates, 35 of the 170 deaths due to cancer (21%) expected within five years of diagnosis were due to the Indigenous: non-Indigenous survival inequality. This percentage was similar when applying 2007-2012 cohort mortality rates (19%; 27 out of 140 deaths). Indigenous people diagnosed with cancer still face a poorer survival outlook than their non-Indigenous counterparts, particularly in the first year after diagnosis. The improving survival outcomes among both Indigenous and non-Indigenous cancer patients, and the decreasing absolute impact of the Indigenous survival disadvantage, should provide increased motivation to continue and enhance current strategies to further reduce the impact of the survival inequalities faced by Indigenous people diagnosed with cancer. PMID- 27186867 TI - Diagnostic Yield of Triple-Rule-Out CT in an Emergency Setting. AB - OBJECTIVE: The objective of the present study is to quantify the diagnostic yield of triple-rule-out (TRO) CT for the evaluation of acute chest pain in emergency department patients. MATERIALS AND METHODS: All TRO CT studies performed at our institution from 2006 to 2015 were reviewed. Scans were performed on a 256-MDCT scanner, with the use of ECG gating and a biphasic contrast injection. Radiology reports were reviewed to identify diagnoses that could explain chest pain, including coronary and noncoronary diagnoses, and significant incidental findings that did not account for the patient's presentation. The total numbers of coronary and noncoronary diagnoses and incidental findings were calculated. RESULTS: Four of 1196 total cases that were identified were excluded from the study because of inadequate image quality. A total of 970 patients (81.4%) had a negative study result without a significant coronary or noncoronary diagnosis. A total of 139 patients (11.7%) had significant coronary artery disease (50% stenosis or greater). One hundred six patients (8.9%) had a noncoronary diagnosis that could explain chest pain (p < 0.02), most commonly pulmonary embolism (28 patients [2.3%]), aortic aneurysm (24 patients [2.0%]), or pneumonia (20 patients [1.7%]). Thirty cases (27.3%) of pulmonary embolism and aortic pathologic findings would not have been detected with coronary CT angiography because of unopacified right-side circulation or limited z-axis coverage. A total of 528 incidental findings not considered to explain chest pain were noted in 418 patients (35.1%). CONCLUSION: In 8.9% of patients, TRO CT detected a significant noncoronary diagnosis that could explain acute chest pain, including pathologic findings that would not be identified on dedicated coronary CT angiography. PMID- 27186866 TI - Can fetal left ventricular modified myocardial performance index predict adverse perinatal outcomes in intrahepatic cholestasis of pregnancy? AB - OBJECTIVE: To investigate fetal left ventricular function using the left ventricular modified myocardial performance index (mod-MPI) and E wave/A wave peak velocity (E/A) ratio, and to explore the success of mod-MPI in the prediction of adverse perinatal outcomes in intrahepatic cholestasis of pregnancy (ICP). METHODS: Forty-one ICP cases were compared with 41 gestational age-matched healthy controls. Opening and closing clicks of the mitral and aortic valves were used to define the three time periods [ejection time (ET), isovolumetric contraction time (ICT) and isovolumetric relaxation time (IRT)], which were employed in the calculation of mod-MPI [mod-MPI = (ICT + IRT)/ET]. The E/A ratio was calculated as well. RESULTS: Fetal left ventricular mod-MPI values were significantly higher in the ICP group compared to controls (0.56 +/- 0.09 versus 0.37 +/- 0.04, p < 0.001), whereas the E/A ratio was lower (0.62 +/- 0.11 versus 0.69 +/- 0.10, p = 0.011). The optimal cutoff level for mod-MPI in prediction of adverse perinatal outcomes was >0.48 [sensitivity: 81.8%, specificity: 67.6%, area under the curve (AUC): 0.750, 95% CI: 0.613-0.887, p = 0.008]. CONCLUSIONS: Fetuses of ICP cases have significant left ventricular dysfunction. Mod-MPI can be used in the prediction of adverse perinatal outcomes in ICP. PMID- 27186868 TI - In clinical care, volume matters. PMID- 27186869 TI - Surgical Management of Giant Cell Tumors in Temporomandibular Joint Region Involving Lateral Skull Base: A Multidisciplinary Approach. AB - PURPOSE: Giant cell tumors (GCTs) in the temporomandibular joint (TMJ) region invading the lateral skull base are relatively uncommon. The management of these lesions is still controversial because of their proximity to vital neurovascular structures. Although sporadically reported, the clinical outcomes of such disease after surgery are still largely unknown. MATERIALS AND METHODS: We retrospectively reviewed the records of 28 patients with resectable GCTs in the TMJ region involving the lateral skull base treated from 1994 to 2013. A multidisciplinary team, formed by oral and maxillofacial surgeons, neurosurgeons, and otorhinolaryngologists, had surgically treated all these patients by craniomaxillofacial resection. Clinical variables, different treatment modalities, and outcomes are compared. Representative cases also are presented. RESULTS: Our case series consisted of 15 male and 13 female patients with a median age of 41 years. The median follow-up duration for our series was 5.4 years (range, 0.8-18.5 years). The average tumor size measured 8.6 cm. Most of the GCTs (n = 19, 67.9%) extended through the skull base bones into the brain parenchyma and other surrounding soft tissues. Titanium meshes for cranioplasty of skull base bones was used in 9 patients (32.1%), whereas temporalis fascia (n = 5, 17.9%) or free flaps (n = 6, 21.4%) were used more frequently for duraplasty. A postoperative cerebrospinal fluid leak was found in only 1 patient. During follow-up, the local control rate reached 85.7%. Thoroughness of tumor resection (hazard ratio, 15.763; 95% confidence interval, 1.630-152.437; P = .017) was found to be associated with recurrence-free survival. CONCLUSIONS: Craniomaxillofacial surgery for GCTs in the TMJ region invading the skull base is feasible in selected patients. A meticulous plan via a multidisciplinary approach is mandatory for the success of such treatment. PMID- 27186870 TI - Is Alloplastic Temporomandibular Joint Reconstruction a Viable Option in the Surgical Management of Adult Patients With Idiopathic Condylar Resorption? AB - PURPOSE: Idiopathic condylar resorption (ICR) presents diagnostic and therapeutic challenges to practitioners because of the rarity of the condition, progressive deformity, and simultaneous involvement of skeletal, occlusal, and articular disorders. The objective of this study was to report clinical outcomes after prosthetic replacement of the temporomandibular joint (TMJ) for the management of ICR. PATIENTS AND METHODS: A retrospective analysis of patients with ICR managed by bilateral total TMJ replacement and concomitant mandibular advancement with or without maxillary surgery was performed using data gathered from medical records. The primary treatment outcomes of interest were 1) correction of anterior open bite malocclusion, 2) mandibular advancement, and 3) increase in posterior facial height. Secondary outcomes included subjective assessment of pain, dietary restrictions, and functional disability and objective evaluations of TMJ sounds, occlusal relation, mandibular range of motion, cranial nerve VII injury, and objectionable scarring. Radiographs were used to measure surgical change and relapse. RESULTS: Twenty-one patients met the inclusion criteria for this retrospective study. The average patient age was 25.6 years (range, 22 to 32 yr) and mean follow-up was 6.2 years (range, 5 to 12 yr). Mean mandibular advancement at the B point was 24.3 mm and mean change in occlusal plane was -10.2 degrees . Sixteen patients (76%) underwent maxillary orthognathic surgery for posterior downgrafting with rigid fixation and grafting. Long-term follow-up showed excellent stability of surgical movements with a decrease in TMJ and myofascial pain, headaches, and dietary restrictions. CONCLUSIONS: Patients with ICR can be effectively treated using total TMJ prostheses with maxillary orthognathic surgery when indicated for the correction of an associated dentofacial deformity. Use of alloplastic joint prostheses allows for the execution of large mandibular advancements in a predictable and accurate manner with a meaningful decrease in symptoms of TMJ dysfunction. PMID- 27186871 TI - Piezotome Rhinoplasty Reduces Postsurgical Morbidity and Enhances Patient Satisfaction: A Multidisciplinary Clinical Study. AB - PURPOSE: Experimental and clinical studies in various fields of oral and maxillofacial surgery suggest the use of piezotomes to reduce postsurgical morbidity and enhance healing. The aim of the study was to investigate if rhinoplasty surgery with piezotomes might decrease postsurgical morbidity and increase overall patient satisfaction when compared with rhinoplasty with traditional instruments and protocols. MATERIALS AND METHODS: In this prospective clinical study, patients in a cosmetic surgery department, ear-nose-throat (ENT) department, and the department for maxillofacial surgery, scheduled for cosmetic reductive rhinoplasty, underwent rhinoplasty with traditional instruments or an ultrasonic surgical device called a "piezotome." Before rhinoplasty, all patients were evaluated by the Rhinoplasty Outcome Evaluation (ROE) questionnaire. Staging for ecchymosis/edema and for pain was performed on the seventh day after surgery, and at 6 months after surgery, patients were again evaluated by the ROE score. Female and male patients aged between 24 and 57 years were included; patients had to be free of functional impairments of nasal breathing. Data were anonymized and evaluated with SPSS software (version 22.0; IBM, Armonk, NY) (1-way analysis of variance, Games-Howell post hoc test for primary and secondary outcome evaluation, Levene test of equal variances, t test, and Pearson correlation of primary and secondary outcome evaluation). RESULTS: Eighty-four patients were fully documented by ecchymosis/edema staging, pain staging, and ROE; of these, 51 women and 12 men underwent cosmetic rhinoplasty in a department of plastic and reconstructive surgery; an ENT department; or a department for maxillofacial surgery. A piezotome rhinoplasty was performed in 16 female and 5 male patients. Statistical evaluation verified that there were no significant differences between the three surgical disciplines when a rhinoplasty was performed with traditional instruments (P > .7), but showed that the use of ultrasonic surgical instruments significantly improved immediate postsurgical morbidity in terms of ecchymosis/edema and pain (P < .05), as well as ROE score after 6 months (P < .05). Correlation of ecchymosis/edema and pain with ROE score showed a significant difference (P <= .01) in favor of the piezotome. CONCLUSIONS: The use of ultrasonic surgical devices in reductive rhinoplasty decreases postsurgical morbidity and increases overall patient satisfaction significantly. The results of this study suggest piezotomes to be the surgical instrument of choice not only for oral surgical procedures, but also for cosmetic surgery on facial bones. PMID- 27186872 TI - Report of 2 Cases of Oropharyngeal Injury With the Use of Video Laryngoscopy Techniques. AB - Although the trend toward video laryngoscopy and away from direct laryngoscopy might be associated with a greater likelihood of successful intubation, appropriate training is necessary to prevent injuries. This report describes 2 instances of operator error that resulted in penetrating injury to the soft palate and presents a review of the literature. PMID- 27186873 TI - Postoperative Bleeding Following Dental Extractions in Patients Anticoagulated With Warfarin. AB - PURPOSE: The practicing dentist must frequently advise on the risks involved with dental extractions in the patient taking an anticoagulant. This study assessed the risk of bleeding in a large heterogeneous cohort of patients on warfarin treated by practitioners in training (dental students and junior staff in a teaching hospital). MATERIALS AND METHODS: This was a retrospective case-and control study of 439 patients on warfarin (1,022 extractions) and 439 matched controls (1,049 extractions). Patients with an international normalized ratio (INR) lower than 2.2 had no specific measures, those with an INR 2.2 to 4 received suturing and tranexamic acid mouthwash, and those with an INR higher than 4 did not undergo extraction. Bayesian methods were used to estimate posterior probabilities of bleeding. RESULTS: Of cases, 63% were men, 25% were older than 80 years, 40% had an INR lower than 2.2, and 9% had an INR higher than 3. Nine cases bled 0 to 10 days postoperatively, with 1 requiring admission and transfusion. Significant predictors of bleeding were INR and number of extractions (P < .001 for the 2 comparisons). There were no events of bleeding in controls or cases with an INR lower than 2.2 (95% credible interval [CrI] for difference, -0.7 to 1.6). The posterior mean of bleeding was 1% (CrI, 0.1-2.6) for an INR lower than 2.2, 2.3% (CrI, 0.9-4.5) for an INR of 2.2 to 3, and 8.4% (CrI, 3.5-15) for an INR higher than 3. CONCLUSION: Unselected patients taking an anticoagulant with an INR lower than 2.2 had a similar risk of bleeding as control patients. The risk was approximately 1 in 40 in those with an INR of 2.2 to 3, whereas the risk in patients with an INR higher than 3 was approximately 1 in 11. PMID- 27186874 TI - How Many Temporomandibular Joint Total Joint Alloplastic Implants Will Be Placed in the United States in 2030? AB - PURPOSE: The purpose of this study is to provide a statistical projection of the number of alloplastic temporomandibular joint (TMJ) total joint replacements (TJRs) that will be performed in the United States through the year 2030. MATERIALS AND METHODS: The program directors of all 101 Commission on Dental Accreditation-accredited oral and maxillofacial surgery training programs in the United States were surveyed online by use of a questionnaire developed using Redcap (Chicago, IL) over a 6-week period (February 2015-March 2015). The questionnaire included 19 questions related to each program's TMJ disorder and TMJ TJR curricula, as well as clinical experience. In addition, members of the American Society of Temporomandibular Joint Surgeons were surveyed online using Redcap and via direct survey forms. Moreover, requests for the total number of TMJ TJR devices produced and implanted during the same period were made to the 3 manufacturers of Food and Drug Administration-approved TMJ TJR devices in the United States. RESULTS: The response rate among program directors was 52.5%, and the total number of TMJ TJR devices implanted in oral and maxillofacial surgery programs in 2005 was 412. This total increased by 38% to 572 in 2014. Statistically, this projects an increase of 58% over the next 16 years to 902 TMJ TJR operations by 2030 (95% prediction limits, 768 and 1,037). The total number of TMJ TJR devices distributed by one manufacturer increased from 430 in the year 2000 to 1,004 in 2014 (133%). By use of these data, statistically over the next 16 years, the number of TMJ TJR devices distributed by this company is projected to be 1,658 (95% prediction limits, 1,380 and 1,935). CONCLUSIONS: The data presented in this study show an increasing demand for the use of TMJ TJR devices in the management of end-stage TMJ disorders to the year 2030. PMID- 27186875 TI - Implementation of a Zebrafish Health Program in a Research Facility: A 4-Year Retrospective Study. AB - In the past two decades, zebrafish (Danio rerio)-based research has contributed to significant scientific advances. Still, husbandry and health programs did not evolve at the same pace, as evidenced by the absence of general guidelines. Health monitoring is essential to animal welfare, to permit animal exchanges across facilities, to contribute to robust experimental results, and for data reproducibility. In this study, we report a health program implemented in a zebrafish research facility to prevent, monitor, and control pathogen, and disease dissemination. This program includes quarantine, routine health screening of sentinels, and nonroutine screenings of retired animals and sick/moribund individuals. An extensive list of clinical signs, lesions, and pathogens was monitored based on: daily observation of fish, necropsy, histology, and bacterial culture. The results indicate that the combined analysis of sentinels with the evaluation of sick/moribund animals enables a comprehensive description not only of pathogen prevalence but also of clinical and histopathologic lesions of resident animals. The establishment of a quarantine program revealed to be effective in the reduction of Pseudoloma neurophilia frequency in the main aquaria room. Finally, characterization of the colony health status based on this multiapproach program shows a low prevalence of lesions and pathogens in the facility. PMID- 27186876 TI - Ethanol and phenanthrene increase the biomass of fungal assemblages and decrease plant litter decomposition in streams. AB - Fungi, particularly aquatic hyphomycetes, have been recognized as playing a dominant role in microbial decomposition of plant litter in streams. In this study, we used a microcosm experiment with different levels of fungal diversity (species number and identity) using monocultures and combinations with up to five aquatic hyphomycete species (Articulospora tetracladia, Tricladium splendens, Heliscus submersus, Tetrachaetum elegans and Flagellospora curta) to assess the effects of ethanol and phenanthrene on three functional measures: plant litter decomposition, fungal biomass accrual and reproduction. Alder leaves were conditioned by fungi for 7days and then were exposed to phenanthrene (1mgL(-1)) dissolved in ethanol (0.1% final concentration) or ethanol (at the concentration used to solubilise phenanthrene) for further 24days. Exposure to ethanol alone or in combination with phenanthrene decreased leaf decomposition and fungal reproduction, but increased fungal biomass produced. All aspects of fungal activity varied with species number. Fungal activity in polycultures was generally higher than that expected from the sum of the weighted performances of participating species in monoculture, suggesting complementarity between species. However, the activity of fungi in polycultures did not exceed the activity of the most productive species either in the absence or presence of ethanol alone or with phenanthrene. PMID- 27186877 TI - Phthalates in dormitory and house dust of northern Chinese cities: Occurrence, human exposure, and risk assessment. AB - Phthalates are widely used chemicals in household products, which severely affect human health. However, there were limited studies emphasized on young adults' exposure to phthalates in dormitories. In this study, seven phthalates were extracted from indoor dust that collected in university dormitories in Harbin, Shenyang, and Baoding, in the north of China. Dust samples were also collected in houses in Harbin for comparison. The total concentrations of phthalates in dormitory dust in Harbin and Shenyang samples were significantly higher than those in Baoding samples. The total geometric mean concentration of phthalates in dormitory dust in Harbin was lower than in house dust. Di-(2-ethylhexyl) phthalate (DEHP) was the most abundant phthalate in both dormitory and house dust. The daily intakes of the total phthalates, carcinogenic risk (CR) of DEHP, hazard index (HI) of di-isobutyl phthalate (DiBP), dibutyl phthalate (DBP), and DEHP were estimated, the median values for all students in dormitories were lower than adults who live in the houses. Monte Carlo simulation was applied to predict the human exposure risk of phthalates. HI of DiBP, DBP, and DEHP was predicted according to the reference doses (RfD) provided by the United States Environmental Protection Agency (U.S.EPA) and the reference doses for anti androgenicity (RfD AA) developed by Kortenkamp and Faust. The results indicated that the risks of some students had exceeded the limitation, however, the measured results were not exceeded the limitation. Risk quotients (RQ) of DEHP were predicted based on China specific No Significant Risk Level (NSRL) and Maximum Allowable Dose Level (MADL). The predicted results of CR and RQ of DEHP suggested that DEHP could pose a health risk through intake of indoor dust. PMID- 27186879 TI - Corrigendum. PMID- 27186880 TI - Translation, Validation and Cross-Cultural Adaptation of a Simplified-Chinese Version of the Tegner Activity Score in Chinese Patients with Anterior Cruciate Ligament Injury. AB - AIMS: To translate the English version of Tegner Activity Score into a Simplified Chinese version (Tegner-C) and evaluate its psychometric properties. METHODS: Tegner-C was cross-culturally adapted according to established guidelines. The validity and reliability of Tegner-C were assessed in 78 participants, with 19-20 participants in each of the four groups: before anterior cruciate ligament reconstruction (pre-ACLR) group, 2-3 months after ACLR group, 3-12 months after ACLR group, and healthy control group. Each participant was asked to complete the Tegner-C and Chinese version of International Knee Documentation Committee Subjective Knee Form (IKDC-SKF-C) twice, with an interval of 5+/-2 days. Intra class correlation coefficient (ICC2, 1) was used to assess the reliability and Spearman's rank correlation was used for construct validity. RESULTS: The ICC2,1 was higher than 0.90 for all groups except in the pre-ACLR group, for which the ICC2,1 was 0.71 (0.41, 0.87) (All with p<0.001). The absolute reliability as evaluated by the smallest detectable change was 0.43, 2.12, 0.89, and 0.44 for the healthy control group, pre-ACLR group, 2-3 months after ACLR group, and 3-12 months after ACLR group, respectively. Neither a ceiling effect nor a floor effect was observed for any group. Significant difference was observed for both Tegner-C and IKDC-SKF-C scores between the control and the other three groups (all with p<0.001), and between pre-ACLR and the 2-3 months after ACLR group (p<0.001). CONCLUSIONS: Tegner-C demonstrated comparable psychometric properties to the original English version and thus is reliable and valid for Chinese speaking patients with ACL injury. PMID- 27186881 TI - Magnetic Resonance Imaging-Guided High-Intensity Focused Ultrasound Ablation of Uterine Fibroids: Effect of Bowel Interposition on Procedure Feasibility and a Unique Bowel Displacement Technique. AB - PURPOSE: To evaluate the effect of bowel interposition on assessing procedure feasibility, and the usefulness and limiting conditions of bowel displacement techniques in magnetic resonance imaging-guided high-intensity focused ultrasound (MR-HIFU) ablation of uterine fibroids. MATERIALS AND METHODS: Institutional review board approved this study. A total of 375 screening MR exams and 206 MR HIFU ablations for symptomatic uterine fibroids performed between August 2010 and March 2015 were retrospectively analyzed. The effect of bowel interposition on procedure feasibility was assessed by comparing pass rates in periods before and after adopting a unique bowel displacement technique (bladder filling, rectal filling and subsequent bladder emptying; BRB maneuver). Risk factors for BRB failure were evaluated using logistic regression analysis. RESULTS: Overall pass rates of pre- and post-BRB periods were 59.0% (98/166) and 71.7% (150/209), and in bowel-interposed cases they were 14.6% (7/48) and 76.4% (55/72), respectively. BRB maneuver was technically successful in 81.7% (49/60). Through-the-bladder sonication was effective in eight of eleven BRB failure cases, thus MR-HIFU could be initiated in 95.0% (57/60). A small uterus on treatment day was the only significant risk factor for BRB failure (B = 0.111, P = 0.017). CONCLUSION: The BRB maneuver greatly reduces the fraction of patients deemed ineligible for MR HIFU ablation of uterine fibroids due to interposed bowels, although care is needed when the uterus is small. PMID- 27186878 TI - Factors Associated with Halitosis in White-Collar Employees in Shanghai, China. AB - OBJECTIVE: To investigate the factors associated with halitosis in Chinese white collar employees. MATERIALS AND METHODS: Subjects in three randomly selected office buildings in Shanghai, China, were enrolled in this cross-sectional study using cluster random sampling. Oral malodor was assessed by measuring volatile sulfur compounds (VSCs) with a portable sulfide monitor. Subjects' oral health, including dental caries, periodontal status, and tongue coating, was evaluated clinically. A questionnaire was used to obtain information about participants' demographic characteristics, oral hygiene habits, and health behaviors. RESULTS: Of the 805 subjects invited to participate in this study, 720 were enrolled (89.4% response rate). Data from these subjects were used for statistical analyses. The prevalence of halitosis was 33.2%. In the final regression model, halitosis was significantly related to tongue coating thickness, periodontal pocket depth, no food consumption within 2 hours prior to oral examination, and less intake frequency of sweet foods. CONCLUSIONS: In this Chinese white-collar population, tongue coating and periodontal disease were associated with halitosis. Oral hygiene education should be provided at the population level to encourage the maintenance of oral health and fresh breath. Consumption of sweet foods may reduce VSC production, although this finding requires further investigation. PMID- 27186884 TI - Forests, Trees, and Micronutrient-Rich Food Consumption in Indonesia. AB - Micronutrient deficiency remains a serious problem in Indonesia with approximately 100 million people, or 40% of the population, suffering from one or more micronutrient deficiencies. In rural areas with poor market access, forests and trees may provide an essential source of nutritious food. This is especially important to understand at a time when forests and other tree-based systems in Indonesia are being lost at unprecedented rates. We use food consumption data from the 2003 Indonesia Demographic Health Survey for children between the ages of one and five years and data on vegetation cover from the Indonesian Ministry of Forestry to examine whether there is a relationship between different tree dominated land classes and consumption of micronutrient-rich foods across the archipelago. We run our models on the aggregate sample which includes over 3000 observations from 25 provinces across Indonesia as well as on sub-samples from different provinces chosen to represent the different land classes. The results show that different tree-dominated land classes were associated with the dietary quality of people living within them in the provinces where they were dominant. Areas of swidden/agroforestry, natural forest, timber and agricultural tree crop plantations were all associated with more frequent consumption of food groups rich in micronutrients in the areas where these were important land classes. The swidden/agroforestry land class was the landscape associated with more frequent consumption of the largest number of micronutrient rich food groups. Further research needs to be done to establish what the mechanisms are that underlie these associations. Swidden cultivation in is often viewed as a backward practice that is an impediment to food security in Indonesia and destructive of the environment. If further research corroborates that swidden farming actually results in better nutrition than the practices that replace it, Indonesian policy makers may need to reconsider their views on this land use. PMID- 27186882 TI - Molecular Mechanisms of Malignant Transformation by Low Dose Cadmium in Normal Human Bronchial Epithelial Cells. AB - Cadmium is a carcinogenic metal, the mechanisms of which are not fully understood. In this study, human bronchial epithelial cells were transformed with sub-toxic doses of cadmium (0.01, 0.05, and 0.1 MUM) and transformed clones were characterized for gene expression changes using RNA-seq, as well as other molecular measurements. 440 genes were upregulated and 47 genes were downregulated in cadmium clones relative to control clones over 1.25-fold. Upregulated genes were associated mostly with gene ontology terms related to embryonic development, immune response, and cell movement, while downregulated genes were associated with RNA metabolism and regulation of transcription. Several embryonic genes were upregulated, including the transcription regulator SATB2. SATB2 is critical for normal skeletal development and has roles in gene expression regulation and chromatin remodeling. Small hairpin RNA knockdown of SATB2 significantly inhibited growth in soft agar, indicating its potential as a driver of metal-induced carcinogenesis. An increase in oxidative stress and autophagy was observed in cadmium clones. In addition, the DNA repair protein O6 methylguanine-DNA-methyltransferase was depleted by transformation with cadmium. MGMT loss caused significant decrease in cell viability after treatment with the alkylating agent temozolomide, demonstrating diminished capacity to repair such damage. Results reveal various mechanisms of cadmium-induced malignant transformation in BEAS-2B cells including upregulation of SATB2, downregulation of MGMT, and increased oxidative stress. PMID- 27186883 TI - Nested Association Mapping of Stem Rust Resistance in Wheat Using Genotyping by Sequencing. AB - We combined the recently developed genotyping by sequencing (GBS) method with joint mapping (also known as nested association mapping) to dissect and understand the genetic architecture controlling stem rust resistance in wheat (Triticum aestivum). Ten stem rust resistant wheat varieties were crossed to the susceptible line LMPG-6 to generate F6 recombinant inbred lines. The recombinant inbred line populations were phenotyped in Kenya, South Africa, and St. Paul, Minnesota, USA. By joint mapping of the 10 populations, we identified 59 minor and medium-effect QTL (explained phenotypic variance range of 1% - 20%) on 20 chromosomes that contributed towards adult plant resistance to North American Pgt races as well as the highly virulent Ug99 race group. Fifteen of the 59 QTL were detected in multiple environments. No epistatic relationship was detected among the QTL. While these numerous small- to medium-effect QTL are shared among the families, the founder parents were found to have different allelic effects for the QTL. Fourteen QTL identified by joint mapping were also detected in single population mapping. As these QTL were mapped using SNP markers with known locations on the physical chromosomes, the genomic regions identified with QTL could be explored more in depth to discover candidate genes for stem rust resistance. The use of GBS-derived de novo SNPs in mapping resistance to stem rust shown in this study could be used as a model to conduct similar marker-trait association studies in other plant species. PMID- 27186885 TI - Cholera Incidence and Mortality in Sub-Saharan African Sites during Multi-country Surveillance. AB - BACKGROUND: Cholera burden in Africa remains unknown, often because of weak national surveillance systems. We analyzed data from the African Cholera Surveillance Network (www.africhol.org). METHODS/ PRINCIPAL FINDINGS: During June 2011-December 2013, we conducted enhanced surveillance in seven zones and four outbreak sites in Togo, the Democratic Republic of Congo (DRC), Guinea, Uganda, Mozambique and Cote d'Ivoire. All health facilities treating cholera cases were included. Cholera incidences were calculated using culture-confirmed cholera cases and culture-confirmed cholera cases corrected for lack of culture testing usually due to overwhelmed health systems and imperfect test sensitivity. Of 13,377 reported suspected cases, 34% occurred in Conakry, Guinea, 47% in Goma, DRC, and 19% in the remaining sites. From 0-40% of suspected cases were aged under five years and from 0.3-86% had rice water stools. Within surveillance zones, 0-37% of suspected cases had confirmed cholera compared to 27-38% during outbreaks. Annual confirmed incidence per 10,000 population was <0.5 in surveillance zones, except Goma where it was 4.6. Goma and Conakry had corrected incidences of 20.2 and 5.8 respectively, while the other zones a median of 0.3. During outbreaks, corrected incidence varied from 2.6 to 13.0. Case fatality ratios ranged from 0-10% (median, 1%) by country. CONCLUSIONS/SIGNIFICANCE: Across different African epidemiological contexts, substantial variation occurred in cholera incidence, age distribution, clinical presentation, culture confirmation, and testing frequency. These results can help guide preventive activities, including vaccine use. PMID- 27186886 TI - PD-1/CTLA-4 Blockade Inhibits Epstein-Barr Virus-Induced Lymphoma Growth in a Cord Blood Humanized-Mouse Model. AB - Epstein-Barr virus (EBV) infection causes B cell lymphomas in humanized mouse models and contributes to a variety of different types of human lymphomas. T cells directed against viral antigens play a critical role in controlling EBV infection, and EBV-positive lymphomas are particularly common in immunocompromised hosts. We previously showed that EBV induces B cell lymphomas with high frequency in a cord blood-humanized mouse model in which EBV-infected human cord blood is injected intraperitoneally into NOD/LtSz-scid/IL2Rgammanull (NSG) mice. Since our former studies showed that it is possible for T cells to control the tumors in another NSG mouse model engrafted with both human fetal CD34+ cells and human thymus and liver, here we investigated whether monoclonal antibodies that block the T cell inhibitory receptors, PD-1 and CTLA-4, enhance the ability of cord blood T cells to control the outgrowth of EBV-induced lymphomas in the cord-blood humanized mouse model. We demonstrate that EBV infected lymphoma cells in this model express both the PD-L1 and PD-L2 inhibitory ligands for the PD-1 receptor, and that T cells express the PD-1 and CTLA-4 receptors. Furthermore, we show that the combination of CTLA-4 and PD-1 blockade strikingly reduces the size of lymphomas induced by a lytic EBV strain (M81) in this model, and that this anti-tumor effect requires T cells. PD-1/CTLA-4 blockade markedly increases EBV-specific T cell responses, and is associated with enhanced tumor infiltration by CD4+ and CD8+ T cells. In addition, PD-1/CTLA-4 blockade decreases the number of both latently, and lytically, EBV-infected B cells. These results indicate that PD-1/CTLA-4 blockade enhances the ability of cord blood T cells to control outgrowth of EBV-induced lymphomas, and suggest that PD-1/CTLA-4 blockade might be useful for treating certain EBV-induced diseases in humans. PMID- 27186887 TI - PHASTpep: Analysis Software for Discovery of Cell-Selective Peptides via Phage Display and Next-Generation Sequencing. AB - Next-generation sequencing has enhanced the phage display process, allowing for the quantification of millions of sequences resulting from the biopanning process. In response, many valuable analysis programs focused on specificity and finding targeted motifs or consensus sequences were developed. For targeted drug delivery and molecular imaging, it is also necessary to find peptides that are selective-targeting only the cell type or tissue of interest. We present a new analysis strategy and accompanying software, PHage Analysis for Selective Targeted PEPtides (PHASTpep), which identifies highly specific and selective peptides. Using this process, we discovered and validated, both in vitro and in vivo in mice, two sequences (HTTIPKV and APPIMSV) targeted to pancreatic cancer associated fibroblasts that escaped identification using previously existing software. Our selectivity analysis makes it possible to discover peptides that target a specific cell type and avoid other cell types, enhancing clinical translatability by circumventing complications with systemic use. PMID- 27186889 TI - Regulatory aspects of human radiolabeled mass balance studies in oncology: concise review. AB - Human radiolabeled mass balance studies are performed to obtain information about the absorption, distribution, metabolism, and excretion of a drug in development. The main goals are to determine the route of elimination and major metabolic pathways. This review provides an overview of the current regulatory guidelines concerning human radiolabeled mass balance studies and discusses scientific trends seen in the last decade with a focus on mass balance studies of anticancer drugs. This paper also provides an overview of mass balance studies of anticancer agents that were executed in the last 10 years. PMID- 27186888 TI - Congruent pattern of accessibility identifies minimal pore gate in a non symmetric voltage-gated sodium channel. AB - Opening and closing of the central ion-conducting pore in voltage-dependent ion channels is gated by changes in membrane potential. Although a gate residue in the eukaryotic voltage-gated sodium channel has been identified, the minimal molecular determinants of this gate region remain unknown. Here, by measuring the closed- and open-state reactivity of MTSET to substituted cysteines in all the pore-lining helices, we show that the state-dependent accessibility is delineated by four hydrophobic residues at homologous positions in each domain. Introduced cysteines above these sites do not react with intracellular MTSET while the channels are closed and yet are rapidly modified while the channels are open. These findings, in conjunction with state-dependent metal cross-bridging, support the notion that the gate residues in each of the four S6 segments of the eukaryotic sodium channel form an occlusion for ions in the closed state and are splayed open on activation. PMID- 27186891 TI - Synthesis and Structure of Alkylzinc 3,5-Diphenylpyrazolates: Dramatic Influence of Steric and Solvent Effects. AB - The reaction of R2Zn (R = Et, (t)Bu) with 3,5-diphenylpyrazole results in the formation of three structurally diverse alkylzinc pyrazolates: a novel dinuclear tetrahydrofuran solvate, an unprecedented trimeric structure, and a spiro trinuclear aggregate. Structural analysis of the resulting complexes provides a new look at the aggregation and stabilization of alkylzinc species. PMID- 27186890 TI - Physiological constraints to climate warming in fish follow principles of plastic floors and concrete ceilings. AB - Understanding the resilience of aquatic ectothermic animals to climate warming has been hindered by the absence of experimental systems experiencing warming across relevant timescales (for example, decades). Here, we examine European perch (Perca fluviatilis, L.) from the Biotest enclosure, a unique coastal ecosystem that maintains natural thermal fluctuations but has been warmed by 5-10 degrees C by a nuclear power plant for over three decades. We show that Biotest perch grow faster and display thermally compensated resting cardiorespiratory functions compared with reference perch living at natural temperatures in adjacent waters. However, maximum cardiorespiratory capacities and heat tolerance limits exhibit limited or no thermal compensation when compared with acutely heated reference perch. We propose that while basal energy requirements and resting cardiorespiratory functions (floors) are thermally plastic, maximum capacities and upper critical heat limits (ceilings) are much less flexible and thus will limit the adaptive capacity of fishes in a warming climate. PMID- 27186892 TI - Early investigational tubulin inhibitors as novel cancer therapeutics. AB - INTRODUCTION: Microtubules represent one of the most logical and strategic molecular targets amongst the current targets for chemotherapy, alongside DNA. In the past decade, tubulin inhibitors as cancer therapeutics have been an area of focus due to the improved understanding and biological relevance of microtubules in cellular functions. Fueled by the objective of developing novel chemotherapeutics and with the aim of establishing the benefits of tubulin inhibition, several clinical trials have been conducted with others ongoing. AREA COVERED: At present, the antitubulin development pipeline contains an armful of agents under clinical investigation. This review focuses on novel tubulin inhibitors as cancer therapeutics. The article covers the agents which have completed the phase II studies along with the agents demonstrating promising results in phase I studies. EXPERT OPINION: Countless clinical trials evaluating the efficacy, safety and pharmacokinetics of novel tubulin inhibitors highlights the scientific efforts being paid to establish their candidature as cancer therapeutics. Colchicine binding site inhibitors as vascular disrupting agents (VDAs) and new taxanes appear to be the most likely agents for future clinical interest. Numerous agents have demonstrated clinical benefits in terms of efficacy and survival in phase I and II studies. However conclusive benefits can only be ascertained on the basis of phase III studies. PMID- 27186893 TI - Multiplexed, Patterned-Paper Immunoassay for Detection of Malaria and Dengue Fever. AB - Multiplex assays detect the presence of more than one analyte in a sample. For diagnostic applications, multiplexed tests save healthcare providers time and resources by performing many assays in parallel, minimizing the amount of sample needed and improving the quality of information acquired regarding the health status of a patient. These advantages are of particular importance for those diseases that present with general, overlapping symptoms, which makes presumptive treatments inaccurate and may put the patient at risk. For example, malaria and dengue fever are febrile illnesses transmitted through mosquito bites, and these common features make it difficult to obtain an accurate diagnosis by symptoms alone. In this manuscript, we describe the development of a multiplexed, patterned paper immunoassay for the detection of biomarkers of malaria and dengue fever: malaria HRP2, malaria pLDH, and dengue NS1 type 2. In areas coendemic for malaria and dengue fever, this assay could be used as a rapid, point-of-care diagnostic to determine the cause of a fever of unknown origin. The reagents required for each paper-based immunoassay are separated spatially within a three dimensional device architecture, which allows the experimental conditions to be adjusted independently for each assay. We demonstrate the analytical performances of paper-based assays for each biomarker and we show that there is no significant difference in performance between the multiplexed immunoassay and those immunoassays performed in singleplex. Additionally, we spiked individual analytes into lysed human blood to demonstrate specificity in a clinically relevant sample matrix. Our results suggest multiplex paper-based devices can be an essential component of diagnostic assays used at the point-of-care. PMID- 27186894 TI - Mapping the Transmission Functions of Single-Molecule Junctions. AB - Charge transport phenomena in single-molecule junctions are often dominated by tunneling, with a transmission function dictating the probability that electrons or holes tunnel through the junction. Here, we present a new and simple technique for measuring the transmission functions of molecular junctions in the coherent tunneling limit, over an energy range of 1.5 eV around the Fermi energy. We create molecular junctions in an ionic environment with electrodes having different exposed areas, which results in the formation of electric double layers of dissimilar density on the two electrodes. This allows us to electrostatically shift the molecular resonance relative to the junction Fermi levels in a manner that depends on the sign of the applied bias, enabling us to map out the junction's transmission function and determine the dominant orbital for charge transport in the molecular junction. We demonstrate this technique using two groups of molecules: one group having molecular resonance energies relatively far from EF and one group having molecular resonance energies within the accessible bias window. Our results compare well with previous electrochemical gating data and with transmission functions computed from first principles. Furthermore, with the second group of molecules, we are able to examine the behavior of a molecular junction as a resonance shifts into the bias window. This work provides a new, experimentally simple route for exploring the fundamentals of charge transport at the nanoscale. PMID- 27186895 TI - VR Online Dating: The New Safe Sex. PMID- 27186896 TI - The Virtual Threat Effect: A Test of Competing Explanations for the Effects of Racial Stereotyping in Video Games on Players' Cognitions. AB - Past research provides evidence that embodying a racially stereotyped African American video game character triggers stereotyped thinking among White players. However, the mechanisms through which virtual racial embodiment of a negatively stereotyped character in a video game impacts stereotyped thinking are still unknown. This study expands on past research and utilizes a between-subjects experimental design to test two possible theoretical explanations: the virtual threat effect and presence. On the one hand, embodying a negatively stereotyped African American character may elicit stereotyped thinking among White players due to the mere exposure to the threatening stereotype. According to this explanation, negative affective response to the threatening stimulus predicts stereotyping. On the other hand, the process of embodying, not just observing, the stereotyped African American character suggests that presence in the game may determine how impactful the game imagery is on White players' stereotyping of African Americans. In this case, level of presence would predict stereotyping. The findings of this study advance research by providing evidence of a psychological explanation for the negative effects of embodying a racially stereotyped video game character on players' race-related perceptions. We conceptualize the "virtual threat effect," which may be applied in additional contexts to understand how embodying stereotyped representations of outgroups in virtual environments may negatively affect individuals' perceptions and support of these groups. PMID- 27186897 TI - An Examination of Users' Influence in Online HIV/AIDS Communities. AB - A network perspective was adopted in this study to identify influential users in an online HIV community in China. Specifically, the indegree centrality, outdegree centrality, betweenness centrality, eigenvector centrality, and clustering coefficient of individuals were evaluated to measure the user influence in such a community. Moreover, this study examined how the digital divide, which is presently one of the major social equity issues in the information society, is associated with an individual's influence within the community. Two networks were formed on the basis of the behavioral data retrieved from the HIV community: the follower-followee network and the post-reply network. In the follower-followee network, members from areas with well-developed technologies demonstrated more connections, received more attention, and secured more critical positions in the network than their counterparts. However, such differences were insignificant in the post-reply network. PMID- 27186898 TI - Self- and Social Motivation to Interact with a Brand on Facebook: The Moderating Roles of Self-Expression and Brand Engagement in a Student Sample. AB - This study investigated the roles of self- and social motivation in interacting with a brand on Facebook. An online survey was conducted using 11 familiar global brands randomly selected from Interbrand's 100 Best Global Brands. The result demonstrated that congruence between actual/ideal self and personality of a brand (i.e., self-motivation) positively influenced users' interaction with a brand on Facebook. In this relationship, self-expressive motivation and brand engagement emerged as moderators. Additionally, social identity as a social motivation positively affected users' interaction with a brand. Although not all components of social motivation influenced users' interaction with a brand, this study showed that two exclusive motivations, self and social, positively influenced users' interaction with a brand on Facebook. Managerial and practical implications were also proposed for marketing a brand on Facebook. PMID- 27186899 TI - Examining Perceived Distance and Personal Authenticity as Mediators of the Effects of Ghost-Tweeting on Parasocial Interaction. AB - A number of high-profile public figures hire ghost-tweeters to post to their social media accounts on their behalf, but no research has examined how this social media practice can affect followers' feelings of connection to the public figures. College students (n = 132) participated in an online experiment to examine the effect of ghost-tweeting practices on parasocial interaction (PSI) with social media figures. Tweet authorship (use of a ghost-tweeter or not) was manipulated. Ghost-tweeting resulted in reduced PSI. Perceptions of distance, but not personal authenticity mediated this effect. However, authenticity and distance did serially mediate the relationship between ghost-tweeting and PSI. These findings shed light on the process of PSI with celebrities and other media figures on social network sites. PMID- 27186902 TI - Optically Active Porphyrin and Phthalocyanine Systems. AB - This review highlights and summarizes various optically active porphyrin and phthalocyanine molecules prepared using a wide range of structural modification methods to improve the design of novel structures and their applications. The induced chirality of some illustrative achiral bis-porphyrins with a chiral guest molecule is introduced because these systems are ideal for the identification and separation of chiral biologically active substrates. In addition, the relationship between CD signal and the absolute configuration of the molecule is analyzed through an analysis of the results of molecular modeling calculations. Possible future research directions are also discussed. PMID- 27186903 TI - Ag(I)-Catalyzed Indolization/C3-Functionalization Cascade of 2-Ethynylanilines via Ring Opening of Donor-Acceptor Cyclopropanes. AB - A AgSbF6-catalyzed cascade involving the ring opening of donor-acceptor cyclopropanes (DACs) preceded by the cyclization of N-protected 2-ethynylaniline is described. The method discloses a step-economy route to 2,3-disubstituted indole, where a Ag catalyst is found to trigger the cascade by activating both alkyne and DACs. Various functionalities at different ends of both substrates offer rapid access to 2,3-disubstituted indole derivatives in one pot in good to excellent yields. Elaboration of the cascade product to useful intermediates is also depicted. PMID- 27186904 TI - Using reverse docking for target identification and its applications for drug discovery. AB - INTRODUCTION: In contrast to traditional molecular docking, inverse or reverse docking is used for identifying receptors for a given ligand among a large number of receptors. Reverse docking can be used to discover new targets for existing drugs and natural compounds, explain polypharmacology and the molecular mechanism of a substance, find alternative indications of drugs through drug repositioning, and detecting adverse drug reactions and drug toxicity. AREAS COVERED: In this review, the authors examine how reverse docking methods have evolved over the past fifteen years and how they have been used for target identification and related applications for drug discovery. They discuss various aspects of target databases, reverse docking tools and servers. EXPERT OPINION: There are several issues related to reverse docking methods such as target structure dataset construction, computational efficiency, how to include receptor flexibility, and most importantly, how to properly normalize the docking scores. In order for reverse docking to become a truly useful tool for the drug discovery, these issues need to be adequately resolved. PMID- 27186905 TI - Conservative treatment of pediatric thoracic and lumbar spinal fractures: outcomes in the sagittal plane. AB - To assess sagittal plane spinopelvic balance and functional outcomes in a pediatric cohort of patients with a thoracic and/or a lumbar fracture treated conservatively. A multicentric study retrospectively reviewed radiological and functional outcomes (mean follow-up 49 months) of 48 patients (mean age 12 years) with thoracic and/or lumbar spinal fractures that occurred between 1996 and 2014. Demographic data and radiological spinopelvic parameters were analyzed. Functional outcome was evaluated by a telephone interview. First, a comparison between the initial and the last follow-up full-spine radiographs was performed for the assessment of bone remodeling and sagittal plane balance. Then, patients were classified into two groups (group 1: Risser<=2 and group 2, Risser>2) to assess the influence of skeletal maturity on the restoration of a correct sagittal balance. A total of 62% of the patients were at skeletal maturity at the final follow-up (Risser 4 and 5). Patients with a Risser grade of 2 or less had a higher remodeling potential. The mean residual local kyphosis in thoracic and lumbar fractures was, respectively, 8.2 degrees and 8.7 degrees . The mean thoracic global kyphosis remains stable at the last follow-up, in contrast to lumbar lordosis, which increased significantly. Sagittal plane global measurements on the basis of the C7-plumbline remained unchanged at the last follow-up. There was no change in the pelvic parameters, except for the sacral slope in the group 1 for patients with a lumbar fracture. The current study confirms a greater correction in younger patients (Risser<=2) in spinal fractures and reported that thoracic fractures have a higher remodeling potential than lumbar fracture. A local kyphosis of almost 10 degrees remained at the last follow-up. However, no deterioration in the sagittal plane balance was found. This suggests compensatory mechanisms in adjacent structures for children and adolescents and excludes the only hypothesis of bone remodeling. PMID- 27186906 TI - Morita-Baylis-Hillman Reaction of alpha,beta-Unsaturated Ketones with Allylic Acetates by the Combination of Transition-Metal Catalysis and Organomediation. AB - An intermolecular Morita-Baylis-Hillman (MBH) reaction of alpha,beta-unsaturated ketones with allylic acetates under the catalysis of 10 mol % of tetrakis(triphenylphosphine)palladium(0) and mediation of tributylphosphine has been developed in the presence of acetic acid, affording the desired alpha coupling products. The MBH reaction has the advantages of good tolerance to many functional groups, excellent regioselectivity and E-stereoselectivity, and moderate to good yields. PMID- 27186917 TI - Biochemical Response to a Moderate Running Bout in Participants With or Without a History of Acute Knee Injury. AB - CONTEXT: Individuals with an acute knee-injury history are 4 times more likely to develop knee osteoarthritis than those without a prior knee injury, and it is unknown why. Individuals with an injury history may exhibit aberrant changes in tissue turnover after physical activity (eg, running), which could lead to osteoarthritis, but this has yet to be determined among young, physically active individuals. OBJECTIVE: To determine collagen degradation and synthesis and inflammatory biomarker concentration levels before exercise and changes in response to an acute running bout in injured participants compared with healthy control participants. DESIGN: Cohort study. SETTING: Research laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of 22 physically active individuals between 18 and 25 years of age were recruited for the study: 11 injured participants (knee injury within 4 years of the study) who were medically cleared for physical activity and 11 matched healthy control participants. MAIN OUTCOME MEASURE(S): The independent variable was group (injured or control). Dependent variables were serum biomarker concentrations for cartilage oligomeric matrix protein, matrix metalloproteinase-13, proinflammatory marker interleukin-1beta, c terminal cross-linking telopeptide of type II collagen, and type II collagen synthesis marker. Each participant provided prerun and postrun blood samples for biomarker-concentration analysis. RESULTS: No group differences existed in serum biomarker concentrations before exercise or in serum biomarker changes from pre-exercise to postexercise. CONCLUSIONS: After an acute bout of moderate intensity running, young, active individuals in a high-risk postinjury population had similar biochemical responses as matched healthy controls. However, the external generalizability of these findings to other exercises and populations has yet to be determined. PMID- 27186920 TI - Long noncoding RNA MALAT1 as a potential novel biomarker in digestive system cancers: a meta-analysis. AB - BACKGROUND: MALAT1 (Metastasis-associated lung adenocarcinoma transcript 1), a newly discovered long non-coding RNA (lncRNA), has been reported to be overexpressed in various cancers. However, the clinical value of MALAT1 in digestive system cancers is unclear. This study was designed to investigate the potential value of MALAT1 as a prognostic biomarker in digestive system cancers. METHODS: We searched the MEDLINE, EMBASE and Cochrane Library databases. All studies that explored the correlation between lncRNA MALAT1 expression and survival in digestive system tumors were selected. A quantitative meta-analysis was performed for the correlation between lncRNA MALAT1 expression and survival in digestive system tumors. RESULTS: Five studies were eligible for analysis, which included 547 patients. Meta-analysis showed that high expression of MALAT1 could predict poor overall survival (OS) in digestive system cancers (pooled HR: 1.85, 95% CI: 1.41-2.43, p < 0.0001). For disease-free survival (DFS), elevated MALAT1 expression was also a significant predictor with a combined HR of 2.28 (95% CI: 1.42-3.67, p = 0.0007). CONCLUSIONS: lncRNA MALAT1 may serve as a potential novel prognostic biomarker in digestive system cancers. PMID- 27186918 TI - Comparison of Gastrointestinal and Rectal Temperatures During Recovery After a Warm-Weather Road Race. AB - CONTEXT: It has been well established that gastrointestinal temperature (TGI) tracks closely with rectal temperature (TREC) during exercise. However, the field use of TGI pills is still being examined, and little is known about how measurements obtained using these devices compare during recovery after exercise in warm weather. OBJECTIVE: To compare TGI and TREC in runners who completed an 11.3-km warm-weather road race and determine if runners with higher TGI and TREC present with greater passive cooling rates during recovery. DESIGN: Cross sectional study. SETTING: Field. PATIENTS OR OTHER PARTICIPANTS: Thirty recreationally active runners (15 men, 15 women; age = 39 +/- 11 years, weight = 68.3 +/- 11.7 kg, body fat = 19.2% +/- 5.0%). MAIN OUTCOME MEASURE(S): The TGI and TREC were obtained immediately after the race and during a 20-minute passive rest at the 2014 Falmouth Road Race (heat index = 26.2 degrees C +/- 0.9 degrees C). Temperatures were taken every 2 minutes during passive rest. The main dependent variables were mean bias and limits of agreement for TGI and TREC, using Bland-Altman analysis, and the 20-minute passive cooling rates for TGI and TREC. RESULTS: No differences were evident between TGI and TREC throughout passive rest (P = .542). The passive cooling rates for TGI and TREC were 0.046 +/ 0.031 degrees C.min(-1) and 0.060 +/- 0.036 degrees C.min(-1), respectively. Runners with higher TGI and TREC at the start of cooling had higher cooling rates (R = 0.682, P < .001 and R = 0.54, P = .001, respectively). The mean bias of TGI during the 20-minute passive rest was -0.06 degrees C +/- 0.56 degrees C with 95% limits of agreement of +/-1.09 degrees C. CONCLUSIONS: After participants completed a warm-weather road race, TGI provided a valid measure of body temperature compared with the criterion measure of TREC. Therefore, TGI may be a viable option for monitoring postexercise-induced hyperthermia, if the pill is administered prophylactically. PMID- 27186919 TI - Return to Play After Exertional Rhabdomyolysis. AB - OBJECTIVE: To outline a 4-phase progressive program that safely and successfully enabled athletes to return to sport without recurrence of exertional rhabdomyolysis symptoms. BACKGROUND: In January 2011, a large cluster of National Collegiate Athletic Association Division I football athletes were evaluated and treated for exertional rhabdomyolysis. After the athletes were treated, the athletic trainers and sports medicine providers were challenged to develop a safe return-to-play program because of the lack of specific reports in the medical literature to direct such activities. TREATMENT: A progressive 4-phase program based on existing recommendations, including guidelines for continued clinical and laboratory monitoring. CONCLUSIONS: Although the actual process of reintegrating players will differ based on each athlete's unique circumstances, this program provides a safe and effective foundation that can be modified based on the response to activity and sport. PMID- 27186921 TI - Contrast enhancement and elastography in endoscopic ultrasound: an update of clinical applications in pancreatic diseases. AB - It is well established that endoscopic ultrasound (EUS) is fundamental in the characterization of many diseases concerning different organs, i.e. pancreaticobiliary diseases, gastrointestinal pathologic conditions, and lymph nodes of unknown origin. It is also well known that many factors can hamper the accuracy of EUS, i.e. biliary stents, chronic pancreatitis, poor operator's expertise. These factors can also lead to suboptimal accuracy when cytological confirmation through EUS-fine needle aspiration (EUS-FNA) is indicated. In recent years, new technological tools have rapidly increased their clinical impact improving the diagnostic power of EUS and EUS-FNA. Among these new tools, the most investigated and useful ones are represented by contrast harmonic-EUS (CH EUS) and EUS-elastography (EUS-E). The purpose of this paper is to provide, through a review of the literature, an update of the applications of CH-EUS and EUS-E in the routine clinical practice in pancreatic diseases. We discussed the first reports and applications of these techniques in our previous review published in Minerva Medica. The applications of CH-EUS and EUS-E to the study of pancreatic diseases appear feasible and safe. The use of both techniques is very simple and does not require any relevant additional workload for the endoscopic personnel. CH-EUS is now considered an important and accurate tool in the diagnosis of solid pancreatic masses and in the differential diagnosis of pancreatic cystic lesions. CH-EUS targeted FNA is an active field of research. However the available studies show that CH-EUS increases FNA accuracy by a little extent, without statistical significance; moreover, CH-EUS FNA showed a trend toward being more efficient vs. simple EUS FNA (less needle passes and more abundance in cytological material) but this trend did not reach statistical significance. On the other hand, the clinical impact of EUS-E in terms of differential diagnosis of pancreatic masses is still under investigation. Chronic pancreatitis evaluation represents the most recent field of application of EUS-E that shows promising results. PMID- 27186922 TI - Long noncoding RNA H19 can predict a poor prognosis and lymph node metastasis: a meta-analysis in human cancer. AB - INTRODUCTION: A long non-coding RNA H19 has been reported to be aberrantly regulated in a wide range of cancers. This meta-analysis was performed to explore the potential value of H19 as a biomarker for cancer prognosis. EVIDENCE ACQUISTION: We searched the electronic databases PubMed and Web of Science (up to Apr 30, 2016) in attention to collect all relevant researches to identify the association of lncRNA H19 with overall survival (OS), disease free survival (DFS) and lymph node metastasis (LNM). EVIDENCE SYNTHESIS: Our findings revealed that high levels of H19 expression could predict poor OS (pooled HR: 1.19, 95% CI: 1.08-1.32, p=0.001) and LNM (pooled OR: 1.810, 95% CI: 1.27-2.59, p=0.001) in multiple cancers. CONCLUSIONS: This meta-analysis showed that overexpression of H19 might potentially serve as a reliable biomarker for poor prognosis in different types of cancers. PMID- 27186923 TI - Management of arrhythmogenic right ventricular cardiomyopathy. AB - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically determined heart muscle disorder, predisposing to sudden cardiac death (SCD), particularly in young patients and athletes. Pathological features include loss of myocytes and fibrofatty replacement of right ventricular myocardium; a biventricular involvement is often observed. The diagnosis of ARVC (prevalence 1:5.000 in the general population) does not rely on a single gold standard test but is achieved using a scoring system, proposed in 2010 by an International Task Force, which encompasses familial and genetic factors, ECG abnormalities, arrhythmias, and structural/functional ventricular alterations. The main goal of treatment is the prevention of SCD. Implantable cardioverter defibrillator (ICD) is the only proven "lifesaving" therapy; however, it is associated with a significant morbidity due to device-related complications and inappropriate ICD interventions. Other treatment options such as life style changes, antiarrhythmic drugs, beta-blockers and catheter ablation may reduce the arrhythmic burden and alleviate symptoms, without evident impact on prevention of SCD. Selection of patient candidates to ICD implantation is the most challenging issue in the clinical management of ARVC. This article reviews the current perspective on management of ARVC, focusing on clinical manifestations, diagnostic criteria, risk stratification and therapeutic strategies of affected patients. PMID- 27186924 TI - Endothelial monolayers on collagen-coated nanofibrous membranes: cell-cell and cell-ECM interactions. AB - Endothelial cells (ECs) form a monolayer lining over the entire vascular wall and play an important role in maintaining vascular homeostasis and cancer metastasis. Loss of proper endothelial function can lead to vascular diseases. Therefore, the endothelial monolayer is particularly important in tissue regeneration and mimicking vascular tissue in vitro. Numerous studies have described the effects of ECs on nanofibers made from a variety of synthetic polymer materials designed to mimic the extracellular matrix (ECM). However, little is known about maintaining the integrity of ECs in in vitro systems. Here we describe polycaprolactone nanofibrous membranes coated with collagen gel that overcome many limitations of conventional nanofibers used for engineering endothelia. We investigated cell-cell and cell-ECM junctional complexes using collagen-coated and conventional nanofibrous membranes. Conventional nanofibrous membranes alone did not form a monolayer with ECs, whereas collagen-coated nanofibrous membranes did. Several concentrations of collagen in the gel coating promoted the formation of cell-cell junctional complexes, facilitated the deposition of laminin, and increased the focal contact organization of ECs. These results suggest the possible use of collagen-coated nanofibrous membranes for vascular tissue engineering applications and a vascular platform for organ-on-a-chip systems. PMID- 27186925 TI - Migrainous vertigo and Meniere's disease: Is there a common genetic background? PMID- 27186926 TI - AAO HNS Tinnitus Miniseminar "Tinnitus Lessons Learned from Combat and Service". Summary 2015. PMID- 27186927 TI - The chemopreventive effect of Ginkgo biloba extract 761 against cisplatin ototoxicity: a pilot study. AB - OBJECTIVE: The purpose of this study was to evaluate, by using distortion product otoacoustic emission test, the action of Ginkgo biloba extract 761, which has a known antioxidant property, as a possible otoprotective against cisplatin induced hearing loss. This prospective and double blinded study was conducted on individuals that were to begin cisplatin treatment in a tertiary university center. They were randomized and allocated in two groups: control group (CG) (n = 07) receiving placebo and cisplatin and study group (SG) (n = 08) receiving Ginkgo biloba extract 761 (240 mg/day) and cisplatin. METHODS: This prospective study was conducted on individuals that were treated by cancer with cisplatin (CDDP) in a tertiary University center. Both groups were instructed to ingest the either placebo or Ginkgo biloba extract 761 before the first cisplatin dose. They were rated and followed up for approximately 90 days. The maximum cumulative cisplatin dosage was 300 mg/m(2). The ototoxic effect was measured with distortion product otoacoustic emissions. Distortion product otoacoustic emissions were recorded before the first cisplatin cycle, 30, 60 and 90 days after the treatment. The average of the amplitude of the signals were calculated and used for comparisons between the groups. RESULTS: Comparisons were made between baseline measurements and those recorded after maximum cumulative CDDP dose. The control group showed smaller distortion product otoacoustic emissions mean amplitudes and smaller signal/noise ratio than the study group (p < 0.05). CONCLUSION: Ginkgo biloba extract 761 probably has antioxidant properties, and might play otoprotective effect against cisplatin ototoxicity in these patients. PMID- 27186928 TI - Risk of hearing alterations in newborns of mothers treated for malaria. AB - INTRODUCTION: The antimalarial drugs can cause irreversible sensorineural hearing loss, and chloroquine phosphate use can be ototoxic to the fetus. OBJECTIVE: To compare the results of hearing screening in newborns of mothers treated for malaria in pregnancy with the results of newborns of mothers untreated and check for increased risk of hearing alterations in the group exposed to treatment. METHOD: Retrospective cohort study which involved 284 infants, 30 in the exposed group to malaria treatment and 254 in the unexposed group, matched for gestational age, birth weight and risk indicators for hearing. They underwent hearing screening by means of transient evoked otoacoustic emissions and/or auditory brainstem response automatic. The variables were collected in an interview with the parents in the health record and the screening database. RESULTS: The prevalence of fail in exposed group (6.7%) was significant when compared with the unexposed group (1.2%). The risk of failing in the hearing screening in the exposed group was 5.64 (CI 1.17 to 27.3). CONCLUSION: Newborns of mothers treated for malaria in pregnancy had a prevalence of fail in hearing screening at 6.7% and 5.64 higher chances to fail than newborns of untreated mothers. PMID- 27186929 TI - The impact of tinnitus on adult Nigerians: health related Quality of Life assessment of sufferers using the Hospital Anxiety and Depression Scale (HADS) and the RAND-36 item health survey 1.0 questionnaire. AB - BACKGROUND: Tinnitus is a distressing ailment with limited options for therapy and affecting the quality of life of sufferers. This study aims to investigate the impact of tinnitus on the health related quality of life, the psychological and emotional wellbeing of patients in our environment. PATIENTS AND METHODS: Consecutive patients with tinnitus presenting to the Otorhinolaryngology outpatient clinic of the Jos University Teaching Hospital and The Ear, Nose and Throat Clinic, Jos were assessed and administered the Hospital Anxiety and Depression Scale (HADS) and the RAND-36 item health survey 1.0 questionnaires. RESULTS: We studied 49 patients, age range 22- 79 years (mean = 36.8; median = 35.5; SD = +/- 12.7) consisting of 22 (44.9%) males and 27 (55.1%) females, male to female ratio of 1:1.2. Patients in the age range 31 to 40 were in the majority (n = 20; 40.4%). Depressive symptoms were recorded in 14 (28.6%) female patients and 11 (22.4%) male patients. Anxiety symptoms were recorded in 18 (36.7%) female patients and 16 (32.6%) male patients. 34 (69.4%) of our patients scored low on all QoL domains except pain levels irrespective of age or gender with statistically significant positive correlations between all the QoL domains studied for all patients (P-value 0.5). Univariate analysis shows statistically significant inverse correlation between emotional distress (anxiety and depression) scores and each of emotional wellbeing scores. CONCLUSIONS: Our study demonstrates high prevalence of tinnitus amongst the younger population in our region especially females with significant reduction in their HRQoL. This should help in raising the awareness of the impact of tinnitus on the QoL, psychological and emotional wellbeing of patients in our region with a view to improving outcome for tinnitus sufferers. We recommend a further study on a larger sample population to determine the socioeconomic impact of tinnitus on the Nigerian population. PMID- 27186930 TI - One-year prevalence and risk factors of tinnitus in children with otological problems. AB - INTRODUCTION: The present study was conducted to find one year prevalence and risk factors of tinnitus in the children (below 18 years) who reported with the ear or hearing related complaint to All India Institute of Speech and hearing, Mysore. METHODS: A retrospective case analysis was carried out by reviewing the case files of those who visited the institute during the above period. RESULTS: The results shown that the tinnitus prevalence was 5.24%. No gender difference was found in children with tinnitus. Further, 79.63% of the children with tinnitus had hearing loss. In addition, 30.23% of the children with tinnitus had mild degree of hearing loss followed by minimal, and moderate degree of hearing loss. Most of these children had conductive, and sensorineural type of hearing loss than mixed type of hearing loss. CONCLUSION: It can be concluded that hearing loss, gender, giddiness, and headache were found to be major risk factors. PMID- 27186932 TI - Prevalence of tinnitus in patients with different temporomandibular disorders symptoms. AB - OBJECTIVE: To compare the prevalence of tinnitus in temporomandibular disorder (TMD) patients affected by either jaw muscle pain, temporomandibular joint (TMJ) internal derangements, or TMJ arthrosis. METHODS: The presence of self-reported tinnitus was assessed in 250 consecutive TMD patients and correlation analysis was performed with clinical TMD signs and symptoms. RESULTS: Tinnitus prevalence in the TMD population was 30.4%. Any significant patterns of correlation were shown for the overall study group, despite a higher tinnitus prevalence in patients with (32.8%) than without masseter pain (24.8%; p = 0.176) as well as in those with (33.7%) than without TMJ arthrosis (26.1%; p = 0.082). Age-stratified analysis showed correlations with masseter pain in older patients (48.3% vs 16; p < 0.05), and with arthrosis in younger patients (57.1% vs 22.2%; p < 0.05). CONCLUSIONS: Any correlation patterns were shown between tinnitus and TMD. Age stratified analysis suggested possible hypotheses for a symptom-specific clinical correlation that should be assessed with future research. PMID- 27186931 TI - Comparison of otoacoustic emissions in patients with tinnitus having normal hearing versus mild hearing loss. AB - INTRODUCTION: Tinnitus is an auditory sensation whose source comes from external stimulus to the body. All studies that can help people with this disorder are very imperative. OBJECTIVE: This study investigates the cochlear function in patients with tinnitus, using Distortion Products Otoacoustic Emissions (DPOAE). MATERIAL AND METHODS: Ears where the subjects referred to feel the tinnitus were considered for the study group while other ears without this sensation of tinnitus acted as a control group. Fifty subjects suffering from unilateral or bilateral tinnitus with normal hearing sensitivity or mild hearing loss were recruited. RESULTS AND CONCLUSIONS: Where comparing the control and study group, the highest percentage of cases of DPOAE detected was in the control group, although these differences were not statistically significant. When the analyzed frequency is the same as the tinnitus frequency, the prevalence of detected DPOAE is in tinnitus ears (50.0 %). In ears where tinnitus was not perceived (73.5 %) a p value of 0.024 (< 0.05) was found, which means that the undetected DPOAE could be influenced by tinnitus. Based on the results, tinnitus might not be caused by changes in the outer hair cells but seems to be affected by that. PMID- 27186933 TI - Association between suppression of otoacoustic emissions and annoyance levels in tinnitus patients with normal hearing. AB - OBJECTIVE: To correlate the annoyance of tinnitus assessed by the Tinnitus Handicap Inventory and on a visual analogue scale with the evoked otoacoustic emission test result in tinnitus patients with normal hearing. STUDY DESIGN: Case control study. SETTING: Public tertiary hospital. SUBJECTS AND METHODS: The sample was initially based on a population of 80 subjects with tinnitus; 20 of them had normal hearing and normal evoked otoacoustic emission test results and comprised the study group. For the purpose of comparison, a control group was formed, which consisted of 17 subjects with no hearing complaints and normal hearing. The participants were submitted to hearing tests, immittance testing and tests for the evaluation of acoustic reflexes, distortion product otoacoustic emissions, transient evoked otoacoustic emissions (TEOAEs), and suppression of TEOAEs. The tests were performed in a sound-treated booth using a linear contralateral noise of 60 dB. The presence of suppression effects was defined when the response amplitude was 0.5 dB or higher. RESULTS: Abnormal evoked otoacoustic emission suppression test results were observed in 52.9% of tinnitus patients and in 32.4% of control subjects (p = 0.086). Suppression effects of TEOAEs were absent in 38.5% of subjects with minimal or mild discomfort and in 61.9% of subjects with moderate or severe discomfort (p = 0.183). CONCLUSION: It was not possible to associate the annoyance caused by tinnitus with the TEOAE suppression test results, although suppression effects were found to decrease with increasing annoyance. PMID- 27186934 TI - Access to hearing health service in Curitiba-PR for the elderly with hearing loss and tinnitus. AB - OBJECTIVE: To determine the incidence of complaints of hearing loss and tinnitus in a group of seniors and their access to hearing health services in the city of Curitiba. METHOD: 578 elderly, attending general practice clinic of two public hospitals in the city. Three questionnaires were applied: for user identification, to check for hearing loss/tinnitus and on access to hearing health services. RESULTS: Of the 578 subjects, 187 (31%) had hearing complaints and 112 (20%) had tinnitus; of these, 72% have never had an audiological evaluation, 12% received treatment for tinnitus without success, 16% reported having hearing aids, 14% had hearing aid devices managed by SUS; 76% of the sample showed the desire to carry out an assessment and be awarded hearing aids; 37% did not know where to seek help. CONCLUSION: The number of individuals with hearing complaints in the studied group is significant, as is the number of people with hearing complaints such as tinnitus who have never had a hearing examination. The access of people to public programs is deficient in this group. PMID- 27186935 TI - Clinical aspects of benign paroxysmal positional vertigo associated with migraine. AB - INTRODUCTION: Whether clinical features in patients with BPPV and migraine differ from patients with BPPV without migraine is unknown. OBJECTIVES: The aim of this study is to compare clinical aspects of patients with or without migraine. MATERIALS AND METHOD: 263 patients with BPPV were enrolled. Patients were investigated in terms of age, gender, symptoms, affected side, type of BPPV and the cure rate. Data were compared in patients with and without migraine. Mean values and standard deviations (+/- SD) were calculated. One way ANOVA test was used for the analysis. Significance was set at p < 0.005. RESULTS: 32 patients had migraine (11.4%). Gender ratio difference between groups was significant (4.2 vs. 1.3). Comparative analysis of average age between groups was not significant (p = 0.069; 38.50 +/- 11.52, 43.38 +/- 13.83). Majority of patients had symptoms less than 2 months and the difference was not significant (78.1% vs. 76%). Comparative analysis of cure rate of the therapeutic maneuvers between 2 groups was not significant (77% vs. 84%). CONCLUSION: Patients with BPPV may have associated migraine. However, this study does not indicate that the presence of migraine is a risk factor for BPPV for the cure since the therapeutic outcome is similar. PMID- 27186936 TI - Erratum. PMID- 27186937 TI - From Nano to Macro through Hierarchical Self-Assembly: The DNA Paradigm. AB - From atoms to molecules and bio-macromolecules, from organelles to cells, tissues, to the whole living system, nature shows us that the formation of complex systems with emergent properties originates from the hierarchical self assembly of single components in guided bottom-up processes. By using DNA as a fundamental building block with well-known self-recognition properties, scientists have developed design rules and physical-chemical approaches for the fully programmable construction of highly organized structures with nanosized features. This review highlights the basic principles of hierarchical self assembly in terms of type and number of distinguishable components and their interaction energies. Such general concepts are then applied to DNA-based systems. After a brief overview of the strategies used until now for the construction of individual DNA units, such as DNA tile motifs and origami structures, their self-association into assemblies of higher order is discussed. Particular emphasis is given to the forces involved in the self-assembly process, understanding and rational combination of which might help to coordinate the single elements of hierarchical structures both in space and time, thus advancing our efforts towards the creation of devices that mimic the complexity and functionality of natural systems. PMID- 27186938 TI - Clinical and safety outcomes of laparoscopic nephrectomy with renal autotransplantation for the loin pain-hematuria syndrome: a 14-year longitudinal cohort study. AB - OBJECTIVE: The objective of this study is to assess clinical and safety outcomes after laparoscopic nephrectomy with autotransplantation for loin pain-hematuria syndrome (LPHS). METHODS: We conducted telephone interviews using structured questionnaires and retrospectively reviewed data on all patients who underwent laparoscopic nephrectomy with autotransplantation for LPHS between January 2000 and May 2014. RESULTS: A total of 24 laparoscopic nephrectomies with renal autotransplantation of 21 patients with LPHS were reviewed. Eighty-three per cent were female with a mean age of 31 years. Postoperatively, graft loss resulting in subsequent nephrectomy occurred in two patients; However, no patients died (median follow-up = 22 months, range 5 to 78 months) or required dialysis (median follow-up = 10 months, range 0.2 to 178 months). There was no significant difference in estimated glomerular filtration rate (eGFR) before and after surgery (100 +/- 22 vs. 97 +/- 23 mL/min/1.73 m2 ; P = 0.37). Among 14 patients (16 autotransplantation) with telephone follow-up, 14 (88%) resulted in pain relief and no operation resulted in worsening pain. All procedures resulted in immediate pain relief; pain recurrence was reported after two procedures. However, those patients had pain-free period up to 36 months. The quality of life was better after 15 (94%) autotransplantation with higher employment rate (44% vs. 69%; P = 0.04). Two patients with graft loss reported better pain control and quality of life. CONCLUSIONS: Renal autotransplantation is a possible treatment option for LPHS refractory to conservative medical treatment. It can offer pain relief and better quality of life. Despite postoperative risk, it seems to be safe for survival and renal outcomes. PMID- 27186939 TI - A Pilot Study Assessing the Effects of Pallidal Deep Brain Stimulation on Sleep Quality and Polysomnography in Parkinson's Patients. AB - OBJECTIVE: Deep Brain Stimulation (DBS) is an established adjunctive surgical intervention to treat poorly controlled motor symptoms in Parkinson's disease (PD). Both surgical targets (the subthalamic nucleus and globus pallidus) have proven equally efficacious in treating motor symptoms but unique differences may exist in effects on nonmotor symptoms. Sleep dysfunction, a common disabling symptom in PD, has only been examined directly in the subthalamic target, demonstrating some beneficial changes in sleep quality. We aimed to explore sleep changes after pallidal stimulation; hypothesizing similar benefits would be seen. METHODS: We performed a prospective nonblinded clinical trial evaluating sleep in five PD patients already slated for pallidal DBS pre and six months postimplantation using validated sleep surveys and polysomnograms (PSGs). Surveys included the Epworth sleepiness scale, PD sleep scale, Insomnia severity index (ISI), and RLS severity scale. RESULTS: Most patients had notable improvements in sleep quality as measured by PSG metrics such as sleep efficiency and latency to sleep but they did not reach statistical significance. Most surveys reflected an improvement as well with the ISI scale showing the most promising trend post pallidal DBS (14.4 +/- 7.02 vs. 9.0 +/- 2.55; p = 0.07). CONCLUSION: In this small pilot trial, pallidal DBS failed to demonstrate statistically significant improvements in sleep metrics postimplantation but did reveal improving trends in several PSG measures including sleep efficiency and latency to sleep onset as well as sleep survey scores. A larger, blinded clinical trial is needed to more definitively determine whether pallidal DBS may benefit sleep. PMID- 27186940 TI - KIT polymorphisms were associated with the risk for head and neck squamous carcinoma in Chinese population. AB - KITLG/KIT pathway plays a vital role in multiple types of human cancer including head and neck squamous cell carcinoma (HNSCC). Genetic variations in KITLG and KIT may affect the expression or function of these genes, thereby modifying cancer risk. In this study, we evaluated the association of KITLG and KIT polymorphisms with HNSCC risk among Chinese population. Twenty-two tagging SNPs in KITLG and KIT genes were genotyped in a case-control study with 576 HNSCC patients and 1552 healthy controls. Logistic regression analyses revealed that an upstream SNP rs6554198 [additive model: adjusted odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.74-0.97, P = 0.019] and two intron SNPs rs2237025 (additive model: adjusted OR = 0.82, 95%CI = 0.70-0.95, P = 0.007), and rs17084687 (additive model: adjusted OR = 0.85, 95%CI = 0.73-0.99, P = 0.042) of KIT were significantly associated with the decreased risk of HNSCC. Combined analysis of the three SNPs showed that subjects carrying the protective alleles had decreased risk of HNSCC in a dose-response manner (Ptrend = 0.001). Furthermore, interaction analyses revealed a significant multiplicative interaction between rs17084687 and drinking on HNSCC risk (P = 0.012). Luciferase activity assay indicated that the allele A of potentially functional rs6554198 led to significantly lower transcription activity of KIT compared to the risk allele G. Summarily, our findings suggested that SNPs in KIT gene may play a role in genetic susceptibility to HNSCC, which may improve our understanding of the pathogenic mechanisms of this disease. (c) 2016 Wiley Periodicals, Inc. PMID- 27186941 TI - Morbidities in non-transfusion-dependent thalassemia. AB - Patients with non-transfusion-dependent thalassemia (NTDT) experience a wide array of clinical complications despite their independence from frequent, regular red blood cell (RBC) transfusions. According to the current understanding of NTDT, these clinical complications stem from the interaction of multiple pathophysiological factors: ineffective erythropoiesis, iron overload, and hypercoagulability. The state of chronic anemia and hypoxia-resulting from ineffective erythropoiesis and hemolysis-leads to the expansion of the erythroid marrow and extramedullary hematopoiesis. The chronic ineffective erythropoiesis also triggers increased intestinal iron absorption and deposition in the liver and endocrine glands despite the lack of transfusional iron load. Patients with NTDT also have a higher incidence of thromboembolic disease, pulmonary hypertension, and silent cerebral ischemia. The treatment of NTDT relies on occasional or more frequent blood transfusions for certain indications (severe infection, pregnancy, and surgery), iron chelation therapy, splenectomy, and hydroxyurea. Splenectomy is no longer routinely performed in all patients with NTDT in light of its association with increased risk of NTDT-related complications. This review focuses on the clinical morbidities associated with NTDT, summarizes the mainstays of treatment, and sheds light on future therapeutic directions in the field. PMID- 27186942 TI - Management of iron overload in hemoglobinopathies: what is the appropriate target iron level? AB - Patients with thalassemia become iron overloaded from increased absorption of iron, ineffective erythropoiesis, and chronic transfusion. Before effective iron chelation became available, thalassemia major patients died of iron-related cardiac failure in the second decade of life. Initial treatment goals for chelation therapy were aimed at levels of ferritin and liver iron concentrations associated with prevention of adverse cardiac outcomes and avoidance of chelator toxicity. Cardiac deaths were greatly reduced and survival was much longer. Epidemiological data from the general population draw clear associations between increased transferrin saturation (and, by inference, labile iron) and early death, diabetes, and malignant transformation. The rate of cancers now seems to be significantly higher in thalassemia than in the general population. Reduction in iron can reverse many of these complications and reduce the risk of malignancy. As toxicity can result from prolonged exposure to even low levels of excess iron, and survival in thalassemia patients is now many decades, it would seem prudent to refocus attention on prevention of long-term complications of iron overload and to maintain labile iron and total body iron levels within a normal range, if expertise and resources are available to avoid complications of overtreatment. PMID- 27186943 TI - Current recommendations for chelation for transfusion-dependent thalassemia. AB - Regular red cell transfusions used to treat thalassemia cause iron loading that must be treated with chelation therapy. Morbidity and mortality in thalassemia major are closely linked to the adequacy of chelation. Chelation therapy removes accumulated iron and detoxifies iron, which can prevent and reverse much of the iron-mediated organ injury. Currently, three chelators are commercially available -deferoxamine, deferasirox, and deferiprone--and each can be used as monotherapy or in combination. Close monitoring of hepatic and cardiac iron burden is central to tailoring chelation. Other factors, including properties of the individual chelators, ongoing transfusional iron burden, and patient preference, must be considered. Monotherapy generally is utilized if the iron burden is in an acceptable or near-acceptable range and the dose is adjusted accordingly. Combination chelation often is employed for patients with high iron burden, iron related organ injury, or where adverse effects of chelators preclude administration of an appropriate chelator dose. The combination of deferoxamine and deferiprone is the best studied, but increasing data are available on the safety and efficacy of newer chelator combinations, including deferasirox with deferoxamine and the oral-only combination of deferasirox with deferiprone. The expanding chelation repertoire should enable better control of iron burden and improved outcomes. PMID- 27186944 TI - Higher all-cause hospitalization among patients with chronic hepatitis C: the Chronic Hepatitis Cohort Study (CHeCS), 2006-2013. AB - In the United States, hospitalization among patients with chronic hepatitis C virus (HCV) infection is high. The healthcare burden associated with hospitalization is not clearly known. We analysed data from the Chronic Hepatitis Cohort Study, an observational cohort of patients receiving care at four integrated healthcare systems, collected from 2006 to 2013 to determine all-cause hospitalization rates of patients with chronic HCV infection and the other health system patients. To compare the hospitalization rates, we selected two health system patients for each chronic HCV patient using their propensity score (PS). Propensity score matching was conducted by site, gender, race, age and household income to minimize differences attributable to these characteristics. We also compared primary reason for hospitalization between chronic HCV patients and the other health system patients. Overall, 10 131 patients with chronic HCV infection and 20 262 health system patients were selected from the 1 867 802 health system patients and were matched by PS. All-cause hospitalization rates were 27.4 (27.0 27.8) and 7.4 (7.2-7.5) per 100 persons-year (PY) for chronic HCV patients and for the other health system patients, respectively. Compared to health system patients, hospitalization rates were significantly higher by site, gender, age group, race and household income among chronic HCV patients (P < 0.001). Compared to health system patients, chronic HCV patients were more likely to be hospitalized from liver-related conditions (RR = 24.8, P < 0.001). Hence, patients with chronic HCV infection had approximately 3.7-fold higher all-cause hospitalization rate than other health system patients. These findings highlight the incremental costs and healthcare burden of patients with chronic HCV infection associated with hospitalization. PMID- 27186945 TI - Single-Amino Acid Modifications Reveal Additional Controls on the Proton Pathway of [FeFe]-Hydrogenase. AB - The proton pathway of [FeFe]-hydrogenase is essential for enzymatic H2 production and oxidation and is composed of four residues and a water molecule. A computational analysis of this pathway in the [FeFe]-hydrogenase from Clostridium pasteurianum revealed that the solvent-exposed residue of the pathway (Glu282) forms hydrogen bonds to two residues outside of the pathway (Arg286 and Ser320), implying that these residues could function in regulating proton transfer. In this study, we show that substituting Arg286 with leucine eliminates hydrogen bonding with Glu282 and results in an ~3-fold enhancement of H2 production activity when methyl viologen is used as an electron donor, suggesting that Arg286 may help control the rate of proton delivery. In contrast, substitution of Ser320 with alanine reduces the rate ~5-fold, implying that it either acts as a member of the pathway or influences Glu282 to permit proton transfer. Interestingly, quantum mechanics/molecular mechanics and molecular dynamics calculations indicate that Ser320 does not play a structural role or indirectly influence the barrier for proton movement at the entrance of the channel. Rather, it may act as an additional proton acceptor for the pathway or serve in a regulatory role. While further studies are needed to elucidate the role of Ser320, collectively these data provide insights into the complex proton transport process. PMID- 27186947 TI - Detection of Human Papillomavirus Genotypes and Major BRCA Mutations in Familial Breast Cancer. AB - Breast cancer is a multistep disease and infection with a DNA virus could play a role in one or more of the steps in this pathogenic process. High-risk human papillomaviruses (HPVs) are the causative agents of several cancers. In this study, we investigated HPV genotypes associated with breast cancer and its relationship with BRCA mutation for the detection of familial breast cancer. We analyzed 84 formalin-fixed, paraffin-embedded tissue blocks from 38 familial breast cancer and 46 nonfamilial breast cancer samples by multiplex polymerase chain reaction and clinical parameters. Overall prevalence of HPV infection was 27 of 84: 10 (37.03%) HPV-16, 9 (29.62%) HPV-18, 4 (14.81%) HPV-11, 1 (3.7%) HPV 31, 1 (3.7%) HPV-33, and 2 (7.4%) HPV35. Furthermore, 17 mtDNA4977 deletions and 5 5382insC mutations were detected from 38 familial breast cancer samples. Our results demonstrate that infection with HPV was prevalent among Iranian women with familial breast cancer and the testing of mtDNA4977 deletions and 5382insC mutations in combination with clinical parameters as major risk factors can serve in the identification of familial breast cancer. PMID- 27186946 TI - Ginkgolide K protects the heart against endoplasmic reticulum stress injury by activating the inositol-requiring enzyme 1alpha/X box-binding protein-1 pathway. AB - BACKGROUND AND PURPOSE: Endoplasmic reticulum (ER) stress is increasingly recognized as an important causal factor of many diseases. Targeting ER stress has now emerged as a new therapeutic strategy for treating cardiovascular diseases. Here, we investigated the effects and underlying mechanism of ginkgolide K (1,10-dihydroxy-3,14-didehydroginkgolide, GK) on cardiac ER stress. EXPERIMENTAL APPROACH: Cell death, apoptosis and ER stress-related signalling pathways were measured in cultured neonatal rat cardiomyocytes, treated with the ER stress inducers tunicamycin, hydrogen peroxide and thapsigargin. Acute myocardial infarction was established using left coronary artery occlusion in mice, and infarct size was measured by triphenyltetrazolium chloride staining. Echocardiography was used to assess heart function and transmission electron microscopy for evaluating ER expansion. KEY RESULTS: Ginkgolide K (GK) significantly decreased ER stress-induced cell death in both in vitro and in vivo models. In ischaemic injured mice, GK treatment reduced infarct size, rescued heart dysfunction and ameliorated ER dilation. Mechanistic studies revealed that the beneficial effects of GK occurred through enhancement of inositol-requiring enzyme 1alpha (IRE1alpha)/X box-binding protein-1 (XBP1) activity, which in turn led to increased ER-associated degradation-mediated clearance of misfolded proteins and autophagy. In addition, GK was also able to partly repress the pro apoptotic action of regulated IRE1-dependent decay and JNK pathway. CONCLUSIONS AND IMPLICATIONS: In conclusion, GK acts through selective activation of the IRE1alpha/XBP1 pathway to limit ER stress injury. GK is revealed as a promising therapeutic agent to ameliorate ER stress for treating cardiovascular diseases. PMID- 27186953 TI - Anti-Diabetic Agent Sodium Tungstate Induces the Secretion of Pro- and Anti Inflammatory Cytokines by Human Kidney Cells. AB - Diabetic kidney disease (DKD) is the major cause of end stage renal disease. Sodium tungstate (NaW) exerts anti-diabetic and immunomodulatory activities in diabetic animal models. Here, we used primary cultures of renal proximal tubule epithelial cells derived from type-2-diabetic (D-RPTEC) and non-diabetic (N RPTEC) subjects as in vitro models to study the effects of NaW on cytokine secretion, as these factors participate in intercellular regulation of inflammation, cell growth and death, differentiation, angiogenesis, development, and repair, all processes that are dysregulated during DKD. In basal conditions, D-RPTEC cells secreted higher levels of prototypical pro-inflammatory IL-6, IL-8, and MCP-1 than N-RPTEC cells, in agreement with their diabetic phenotype. Unexpectedly, NaW further induced IL-6, IL-8, and MCP-1 secretion in both N- and D-RPTEC, together with lower levels of IL-1 RA, IL-4, IL-10, and GM-CSF, suggesting that it may contribute to the extent of renal damage/repair during DKD. Besides, NaW induced the accumulation of IkappaBalpha, the main inhibitor protein of one major pathway involved in cytokine production, suggesting further anti-inflammatory effect in the long-term. A better understanding of the mechanisms involved in the interplay between the anti-diabetic and immunomodulatory properties of NaW will facilitate future studies about its clinical relevance. J. Cell. Physiol. 232: 355-362, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27186954 TI - Mitomycin-C+fluoropyrimidines in heavily pretreated metastatic colorectal cancer: a systematic review and evidence synthesis. AB - Mitomycin-C (MMC) combined with fluoropyrimidines has historically been used for pretreated patients with some activity in this setting, in particular, as third line chemotherapy (CT) or beyond. We have evaluated the efficacy and safety of MMC-based therapy as a further line of CT in advanced colorectal cancer. Prospective or retrospective studies of MMC-based CT were included in the pooled analysis. PubMed, EMBASE, SCOPUS, Web of Science, the Cochrane Library database and CINAHL were searched systematically. The outcomes were progression-free survival, overall survival, overall response rate and grades 3-4 drug-related adverse events. Seventeen trials involving 681 patients were included in the analysis. Overall, the pooled average weighted progression-free survival and overall survival were 2.84 [95% confidence interval (CI) 2.5-3.1] and 7.47 (95% CI 6-8.9) months, respectively. The corresponding pooled overall response rate was 7.2% (95% CI 5.2-9.9%) and the pooled disease control rate was 38.7% (95% CI 31.7-46.3%). The G3-4 neutropenia and anaemia were the most frequent haematological toxicities (range 0-20%). Nonhaematological G3-4 toxicities were compatible with the associated agent. MMC with fluoropyrimidines represents a viable and active combination for pretreated metastatic colorectal cancer patients. It is thus an option when other agents have failed, or are unavailable or not indicated. PMID- 27186955 TI - The Feasibility of Physical Activity Interventions During the Intense Treatment Phase for Children and Adolescents with Cancer: A Systematic Review. AB - BACKGROUND: Physical activity may have benefits for children undergoing intense treatment for cancer, but such programmes are challenging to implement. This systematic review aimed to investigate the feasibly of physical activity interventions during intense cancer treatment for children and adolescents. PROCEDURE: A systematic search of seven electronic databases (Cumulative Index to Nursing and Allied Health Literature, Medical Literature Analysis and Retrieval System Online, Public/Publisher MEDLINE, Psychological Information Database, Sportsdiscuss, Excerpta Medica Database, Allied and Complementary Medicine Database) from 2005 to August 2015 was completed. The risk of bias was assessed using the Downs and Black Checklist and The Critical Review Form-Qualitative Studies. Results were summarised descriptively across eight domains of feasibility: acceptability, demand, implementation, adaptation, practicality, integration, expansion and limited efficiency testing (including effectiveness). RESULTS: Eleven quantitative studies and one qualitative study were identified for inclusion. Physical activity interventions were typically supervised, individualised programmes that prescribed a variety of activity types for hospital inpatients. There was evidence that physical activity interventions during the intense phase of cancer treatment were acceptable to parents and children, safe and successfully implemented. A trend of positive effects across all aspects of functioning was noted. Data were unavailable documenting feasibility for the domains of integration, adaptation and expansion. CONCLUSION: There is preliminary evidence that physical activity interventions are feasible, in that they are acceptable, safe and potentially beneficial for children with cancer but more work needs to be done to understand the most effective ways to implement these types of programmes. PMID- 27186956 TI - Simple and practical screening approach to identify HIV-infected individuals with depression or at risk of developing depression. AB - OBJECTIVES: Studies have shown that depression and other mental illnesses are under-diagnosed among HIV-infected individuals. The aim of this study was to evaluate the use of mental health history and questionnaire-based screening instruments to identify HIV-infected individuals at risk of depression. METHODS: The Beck Depression Inventory II (BDI-II) was used to assess the prevalence and severity of depressive symptoms among HIV-infected individuals attending two out patient clinics in Denmark. HIV-infected individuals with a BDI-II score >= 20 were offered a clinical evaluation by a consultant psychiatrist. The BDI-II score was compared to the outcome of mental health history review, and to results obtained using the European AIDS Clinical Society (EACS) two-item depression screening tool. RESULTS: A total of 501 HIV-infected individuals were included in the study. Symptoms of moderate/major depression (BDI-II score >= 20) were observed in 111 patients (22%); 65 of these patients consulted a psychiatrist, of whom 71% were diagnosed with a co-existing disorder. The BDI-II score was compared to the outcome of a mental health history review, and to results obtained using the European AIDS Clinical Society (EACS) two-item depression screening tool. The two questions showed a sensitivity and specificity of 95% and 68%, respectively, for diagnosis of current depression or risk of depression. A previous psychiatric history and substance abuse were independently associated with an increased risk of depression. CONCLUSIONS: We suggest that the mental health of HIV-infected individuals should be reviewed and a "risk-flag" three step approach should be used (1) to screen routinely with the two verbal questions suggested by the EACS, (2) to identify whether there is a risk of depression and then screen with the BDI-II, and (3) to identify whether there is still a risk and then perform a full evaluation and obtain an accurate psychiatric diagnosis by a psychiatrist. PMID- 27186957 TI - Gossypol-Capped Mitoxantrone-Loaded Mesoporous SiO2 NPs for the Cooperative Controlled Release of Two Anti-Cancer Drugs. AB - Mesoporous SiO2 nanoparticles, MP-SiO2 NPs, are functionalized with the boronic acid ligand units. The pores of the MP-SiO2 NPs are loaded with the anticancer drug mitoxantrone, and the pores are capped with the anticancer drug gossypol. The resulting two-drug-functionalized MP-SiO2 NPs provide a potential stimuli responsive anticancer drug carrier for cooperative chemotherapeutic treatment. In vitro experiments reveal that the MP-SiO2 NPs are unlocked under environmental conditions present in cancer cells, e.g., acidic pH and lactic acid overexpressed in cancer cells. The effective unlocking of the capping units under these conditions is attributed to the acidic hydrolysis of the boronate ester capping units and to the cooperative separation of the boronate ester bridges by the lactate ligand. The gossypol-capped mitoxantrone-loaded MP-SiO2 NPs reveals preferential cytotoxicity toward cancer cells and cooperative chemotherapeutic activities toward the cancer cells. The MCF-10A epithelial breast cells and the malignant MDA-MB-231 breast cancer cells treated with the gossypol-capped mitoxantrone-loaded MP-SiO2 NPs revealed after a time-interval of 5 days a cell death of ca. 8% and 60%, respectively. Also, the gossypol-capped mitoxantrone loaded MP-SiO2 NPs revealed superior cancer-cell death (ca. 60%) as compared to control carriers consisting of beta-cyclodextrin-capped mitoxantrone-loaded (ca. 40%) under similar loading of the mitoxantrone drug. The drugs-loaded MP-SiO2 NPs reveal impressive long-term stabilities. PMID- 27186958 TI - Relationship between obesity and hearing loss. AB - CONCLUSION: Underweight and severe obesity were associated with an increased prevalence of hearing loss in a Korean population. OBJECTIVE: The relationship between weight and hearing loss is unclear. This study, therefore, analyzed the relationship between hearing loss and body mass index (BMI) in a Korean population. METHODS: The prevalence and severity of hearing loss were assessed in 61 052 subjects who underwent health screening examinations, including hearing tests. Subjects were divided into five groups according to BMI (underweight, normal, overweight, obese, and severely obese). The relationships between the prevalence and severity of hearing loss and BMI were analyzed, after adjusting for the effects of age. RESULTS: The rates of mild or greater hearing loss in the underweight, normal, overweight, obese, and severely obese groups were 24.9%, 20.4%, 21.8%, 21.2%, and 24.1%, respectively. Mild severity of hearing loss was the most common in all five groups, followed by moderate, moderately severe, and severe hearing loss, in that order. Multivariate analysis, showed that the odds ratios of hearing loss in the severely obese, and underweight groups, compared with the normal group, were 1.312 and 1.282, respectively. PMID- 27186959 TI - External validation of risk stratification strategy in the use of renal ultrasonography in the evaluation of acute kidney injury. AB - BACKGROUND: Per the American College of Radiology Appropriateness Criteria, renal ultrasound is the most appropriate imaging examination to evaluate patients with acute kidney injury. However, recent studies suggest that renal ultrasound may be more selectively performed, which could lead to reductions in the use of medical imaging. OBJECTIVE: Evaluate a published risk stratification prediction model (the Licurse model) for using renal ultrasound in hospitalized patients with acute kidney injury. DESIGN: Prospective, observational cohort study. SETTING: A 793-bed, quaternary care, academic hospital. PATIENTS: All adult hospitalized patients who underwent renal ultrasound for the indication of acute kidney injury. INTERVENTION/EXPOSURE: None. MEASUREMENTS: Primary outcome was rate of hydronephrosis diagnosed on ultrasound. Secondary outcome was rate of hydronephrosis resulting in urologic intervention. RESULTS: Of 778 patients who underwent renal ultrasonography to evaluate acute kidney injury, hydronephrosis was present in 106 (13.6%); urologic intervention was performed in 23 patients (3.0%). The Licurse model had sensitivity of 91.3% (95% confidence interval [CI]: 73.2%-97.6%) for urologic intervention and 93.4% (95% CI: 87.2%-96.8%) for hydronephrosis, respectively. Specificity was low for urologic intervention (23.0% [95% CI: 20.2-26.2]) and hydronephrosis (25.1% [95% CI: 22.0-28.6]). We estimated that for 22.6% of patients, hydronephrosis could be ruled out based on clinical predictors. CONCLUSIONS: We found that the Licurse renal ultrasonography risk stratification model was sufficiently accurate in classifying patients at risk for ureteral obstruction among hospitalized patients with acute kidney injury. Journal of Hospital Medicine 2016;11:763-767. (c) 2016 Society of Hospital Medicine. PMID- 27186961 TI - DFT Study of the Reaction Mechanisms of Carbon Dioxide and its Isoelectronic Molecules CS2 and OCS Dissolved in Pyrrolidinium and Imidazolium Acetate Ionic Liquids. AB - The reaction mechanisms of CO2 and its isoelectronic molecules OCS and CS2 dissolved in N-butyl-N-methylpyrrolidinium acetate and in 1-butyl-3 methylimidazolium acetate were investigated by DFT calculations in "gas phase". The analysis of predicted multistep pathways allowed calculating energies of reaction and energy barriers of the processes. The major role played by the acetate anion in the degradation of the solutes CS2 and OCS as well as in the capture of OCS and CO2 by the imidazolium ring is highlighted. In both ionic liquids, this anion governs the conversion of CS2 into OCS and of OCS into CO2 through interatomic S-O exchanges between the anion and the solutes with formation of thioacetate anions. In imidazolium acetate, the selective capture of CS2 and OCS by the imidazolium ring competes with the S-O exchanges. From the calculated values of the energy barriers a basicity scale of the anions is proposed. The (13)C NMR chemical shifts of the predicted adducts were calculated and agree well with the experimental observations. It is argued that the scenario issued from the calculated pathways is shown qualitatively to be independent from the functionals and basis set used, constitute a valuable tool in the understanding of chemical reactions taking place in liquid phase. PMID- 27186962 TI - Youngest case of ductal carcinoma in situ arising within a benign phyllodes tumour: A case report. AB - INTRODUCTION: Phyllodes tumour (PT) is a rare tumour of the female breast. The tumour clinically and radiologically mimics the features of a fibroadenoma. Ductal carcinoma in situ (DCIS) in the epithelial component of PT is a very rare finding. PRESENTATION OF CASE: We present youngest ever case of a 23-year-old nulliparous woman with high-grade ductal carcinoma in situ arising within a benign phyllodes tumor. Macroscopically, it is a homogeneous tumour with solid components. Microscopically, it features typical leaf-like pattern with hypercellular stroma with high-grade ductal carcinoma in situ. DISCUSSION: To date, eight such rare cases of benign phyllodes tumour with ductal carcinoma in situ have been documented. We report the youngest case known in literature so far. CONCLUSION: As this is a very rare presentation, it poses several challenges in regard to both management and follow-up. PMID- 27186963 TI - Third trimester abnormal oral glucose tolerance test and adverse perinatal outcome. AB - OBJECTIVE: To compare perinatal outcome of women after third trimester oral glucose tolerance test (GTT) following normal glucose challenge test (GCT) stratified by test results. STUDY DESIGN: Retrospective cohort study of women delivered in a tertiary, university affiliated medical center (2007-2012). Inclusion criteria were women with a normal 50 g GCT (<140 mg/dl) followed by GTT, who delivered a live-born fetus >28 gestational weeks. Gestational diabetes mellitus (GDM) was defined as >=2 pathological values on GTT (Carpenter and Coustan's criteria). Perinatal outcome was stratified by GTT results: normal (if all 4 values were normal), single pathological value or GDM. Logistic regression analysis was utilized to adjust outcomes to potential confounders. RESULTS: Overall, 323 women met inclusion criteria. Of them, 277 (85.8%) had 4 normal values, 32 (9.9%) had a single pathological value and 14 (4.3%) had late-onset GDM. Infants of mothers diagnosed and treated as GDM had lower birth weights, compared to non-diabetics and those with a single pathological value GTT. Mothers with GTT >=1 pathological values had statistically insignificant higher rates of cesarean delivery. However, this difference was not significant after adjustment to potential confounders. CONCLUSION: Treatment of late-onset GDM may lead to lower birthweights, presumably due to glucose control. No association was found with cesarean delivery or neonatal outcome. PMID- 27186960 TI - Leaving Group Ability Observably Affects Transition State Structure in a Single Enzyme Active Site. AB - A reaction's transition state (TS) structure plays a critical role in determining reactivity and has important implications for the design of catalysts, drugs, and other applications. Here, we explore TS structure in the enzyme alkaline phosphatase using hybrid Quantum Mechanics/Molecular Mechanics simulations. We find that minor perturbations to the substrate have major effects on TS structure and the way the enzyme stabilizes the TS. Substrates with good leaving groups (LGs) have little cleavage of the phosphorus-LG bond at the TS, while substrates with poor LGs have substantial cleavage of that bond. The results predict nonlinear free energy relationships for a single rate-determining step, and substantial differences in kinetic isotope effects for different substrates; both trends were observed in previous experimental studies, although the original interpretations differed from the present model. Moreover, due to different degrees of phosphorus-LG bond cleavage at the TS for different substrates, the LG is stabilized by different interactions at the TS: while a poor LG is directly stabilized by an active site zinc ion, a good LG is mainly stabilized by active site water molecules. Our results demonstrate the considerable plasticity of TS structure and stabilization in enzymes. Furthermore, perturbations to reactivity that probe TS structure experimentally (i.e., substituent effects) may substantially perturb the TS they aim to probe, and thus classical experimental approaches such as free energy relations should be interpreted with care. PMID- 27186964 TI - Development of explicit diffraction corrections for absolute measurements of acoustic nonlinearity parameters in the quasilinear regime. AB - In absolute measurements of acoustic nonlinearity parameters, amplitudes of harmonics must be corrected for diffraction effects. In this study, we develop explicit multi-Gaussian beam (MGB) model-based diffraction corrections for the first three harmonics in weakly nonlinear, axisymmetric sound beams. The effects of making diffraction corrections on nonlinearity parameter estimation are investigated by defining "total diffraction correction (TDC)". The results demonstrate that TDC cannot be neglected even for harmonic generation experiments in the nearfield region. PMID- 27186965 TI - Spatial perspectives in the redox code-Mass spectrometric proteomics studies of moonlighting proteins. AB - The Redox Code involves specific, reversible oxidative changes in proteins that modulate protein tertiary structure, interactions, trafficking, and activity, and hence couple the proteome to the metabolic/oxidative state of cells. It is currently a major focus of study in cell biology. Recent studies of dynamic cellular spatial reorganization with MS-based subcellular-spatial-razor proteomics reveal that protein constituents of many subcellular structures, including mitochondria, the endoplasmic reticulum, the plasma membrane, and the extracellular matrix, undergo changes in their subcellular abundance/distribution in response to oxidative stress. These proteins are components of a diverse variety of functional processes spatially distributed across cells. Many of the same proteins are involved in response to suppression of DNA replication indicate that oxidative stress is strongly intertwined with DNA replication/proliferation. Both are replete with networks of moonlighting proteins that show coordinated changes in subcellular location and that include primary protein actuators of the redox code involved in the processing of NAD+ /NADH, NADP+ /NADPH, Cys/CySS, and GSH/GSSG redox couples. Small groups of key proteins such as {KPNA2, KPNB1, PCNA, PTMA, SET} constitute "spatial switches" that modulate many nuclear processes. Much of the functional response involves subcellular protein trafficking, including nuclear import/export processes, vesicle-mediated trafficking, the endoplasmic reticulum/Golgi pathway, chaperone-assisted processes, and other transport systems. This is not visible to measurements of total protein abundance by transcriptomics or proteomics. Comprehensive pictures of cellular function will require collection of data on the subcellular transport and local functions of many moonlighting proteins, especially of those with critical roles in spatial coordination across cells. The proteome-wide analysis of coordinated changes in abundance and trafficking of proteins offered by MS-based proteomics has a unique, crucial role to play in deciphering the complex adaptive systems that underlie cellular function. (c) 2016 Wiley Periodicals, Inc. Mass Spec Rev. PMID- 27186966 TI - A Self-Determination Perspective on Online Health Information Seeking: The Internet vs. Face-to-Face Office Visits With Physicians. AB - This study elucidates the experiential and motivational aspects of online health information beyond the theoretically limited instrumental perspective that dominates the extant literature. Based on a sample of 993 online health information seekers in India, the survey found that online health information seeking offers individuals greater autonomy, competence, and relatedness compared to face-to-face office visits with physicians. According to self-determination theory, individuals are motivated to act by a sense of volition and experience of willingness, validation of one's skills and competencies, and feeling of connection with others who shaped one's decisions. These 3 psychological needs, which motivate individuals to pursue what they innately seek as human beings, help explain why individuals turn online for health information. T tests showed that all 3 self-determination theory constructs -autonomy, competence, and relatedness-were higher for online health information seeking than for face-to face office visits with physicians. A regression analysis found that 2 variables, autonomy and relatedness, explained online health information seeking. Competence was not a significant factor, likely because of competency issues faced by individuals in interpreting, understanding, and making use of online health information. The findings, which do not suggest that online health information seeking would displace physicians as many have feared, offer promise for an integrated system of care. Office visits with physicians would necessarily evolve into an expanded communicative space of health information seeking instead of an alternative channel for health information. PMID- 27186967 TI - Interleukin 10 protects primary melanocyte by activation of Stat-3 and PI3K/Akt/NF-kappaB signaling pathways. AB - Vitiligo is a common melanocytopenic disorder of the skin, with acquired focal depigmentation. Normal human skin relies on melanocytes to provide photoprotection and thermoregulation by producing melanin. Interleukin 10 (IL-10) is a pleiotropic immunoregulatory cytokine drawing more and more researchers' attention. The present study was conducted to investigate the effects of IL-10 on melanocytes and elucidate the underlying mechanisms. We proved that IL-10 play no role in regulating melanogenesis of normal human foreskin-derived epidermal melanocytes (NHEM). IL-10 stimulation activated the JAK/Stat-3 and PI3K/Akt signaling pathways. Moreover, IL-10 treatment increased translocation of p65 NF kappaB into the nuclear compartment, and up-regulated expression of the pro survival proteins Bcl-2 and Bcl-xL. IL-10 restored anti-apoptotic proteins expression and suppressed cytochrome c release in H2O2-induced apoptosis. In conclusion, IL-10 may provide pro-survival cues to melanocytes and be applied in the treatment of vitiligo and other depigmenting disorders. PMID- 27186968 TI - Acute variegate porphyria presenting with reversible cerebral vasoconstriction. PMID- 27186969 TI - Mediated configural learning in rats. AB - Three experiments investigated mediated configural learning in male rats. In Experiment 1, after exposure to audio-visual compounds AX and BY, rats received trials where X was paired with shock, and Y was not. The idea that conditioning with X enables the evoked configural representation of AX to be linked to shock received support from the facts that while AX provoked more fear than BX, there was no difference between BY and AY. Similarly, Experiment 2 showed that after exposure to AX and BY, separate pairings of X and Y with shock resulted in more fear to AX and BY than AY and BX. In Experiment 3, rats in group consistent received separate exposures to A and X in Context C, and B and Y in D, while those in group inconsistent received A and X (and B and Y) in both C and D. After rats had received shocks in both C and D, rats in group consistent showed more fear to AX and BY than to BX and AY, but this was not the case in group inconsistent. These results indicate that configural representations, formed either by presenting auditory and visual stimuli as parts of a compound or in a shared context, are subject to a process of mediated learning. PMID- 27186970 TI - A donor-acceptor triptycene-coumarin hybrid dye featuring a charge separated excited state and AIE properties. AB - A triptycene-coumarin hybrid dye DCT-1 with a 1,4-dimethoxybenzene group as the electron donor and a coumarin fluorophore as the acceptor on the separated fins of a triptycene was synthesized. DCT-1 features a charge separated excited state with emissions sensitive to solvent polarities. Moreover, DCT-1 also exhibits aggregation-induced emission properties in water with excellent photostability and pH-stability for potential cell imaging applications. PMID- 27186971 TI - Huaiqihuang may protect from proteinuria by resisting MPC5 podocyte damage via targeting p-ERK/CHOP pathway. AB - The purpose of this study was to investigate the potential effects of Huaiqihuang (HQH) granule, a Chinese herbal medicine, in treating proteinuria and to reveal its possible mechanism. MPC5 podocytes were cultured in vitro at 37 degrees C and induced with tunicamycin (TM). The TM-induced cells were treated with HQH at different concentrations. The cell proliferation was detected using the MTT assay. The optimal effective dose of HQH for MPC5 cells was determined by the MTT assay and LDH assay respectively. The influences of HQH on the proteinuria related protein expression and the signaling pathway associated protein expression were also detected using quantitative reverse transcription PCR and Western blotting analysis. The results showed that the MPC5 cell model was successfully constructed in vitro. The HQH application could improve the harmful effects induced by TM on the MPC5 cells, including promoted cell proliferation and suppressed cell apoptosis. Furthermore, the protein expression, including podocin, nephrin, and synaptopodin was down-regulated by the TM treatment in the MPC5 cells. On contrary, the expression of these proteins was up-regulated after the HQH application. Also, the effect of TM on integrin alpha3 and integrin beta1 expressions was also reversed by the HQH treatment. Moreover, the HQH application decreased the expression of p-ERK and DNA-damage-inducible transcript 3 (DDIT3 or CHOP) in the MPC5 cells, which was opposite to the effect observed in the cells treated with TM. Taken together, our study suggest that HQH application may protect podocytes from TM damage by suppressing the p-ERK/CHOP signaling pathway. PMID- 27186972 TI - Thiol/disulfide homeostasis in patients with ankylosing spondylitis. AB - Ankylosing spondylitis (AS) is a chronic inflammatory disease. In many inflammatory diseases, increased production of pro-inflammatory cytokines is associated with an increase in oxidative stress mediators. Thiol/disulfide homeostasis is a marker for oxidative stress. The aim of this study was to examine the dynamic thiol/disulfide homeostasis in AS. Sixty-nine patients with AS and 60 age- and sex-matched controls were included in the study. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and visual analogue scale (VAS) were used to determine the disease activity. Native thiol, total thiol, and disulfide levels were measured with a novel automated method recently described by Erel and Neselioglu. The aforementioned method is also optionally manual spectrophotometric assay. The total thiol levels were significantly lower in the AS group compared with the control group (p = 0.03). When the patients were divided into active (n = 35) and inactive (n = 34) subgroups using BASDAI scores, the native plasma thiol and total thiol levels were significantly lower in the active AS patients compared to the inactive AS patients (p = 0.02, p = 0.03 respectively). There was a negative correlation between the plasma native thiol levels and VAS, BASDAI scores. Thiol/disulfide homeostasis may be used for elucidating the effects of oxidative stress in AS. Understanding the role of thiol/disulfide homeostasis in AS might provide new therapeutic intervention strategies for patients. PMID- 27186973 TI - Glutathione protects against hepatic injury in a murine model of primary Sjogren's syndrome. AB - Primary Sjogren's syndrome (pSS) is a systemic autoimmune disease which may cause complications such as hepatic dysfunction and injury. As an important antioxidant, reduced glutathione (GSH) has been reported protecting against hepatic injury induced by some diseases, but the role of GSH in pSS is poorly understood. This study aims at investigating the role of GSH in hepatic injury during pSS. A murine model of pSS, non-obese diabetic (NOD) mice, was used for GSH administration via tail intravenous injection. Enzyme-linked immunosorbent assay (ELISA) was performed to detect serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), as well as the levels of GSH, tumor necrosis factor, interleukin (IL) 10, integrin alpha M, IL1B, malondialdehyde, nicotinamide adenine dinucleotide phosphate oxidase 4, and superoxide dismutases in hepatocyte homogenates. Hematoxylin-eosin staining was performed to observe hepatic histology. The results showed that serum AST and ALT levels were up regulated in the NOD mice (p = 0.0021 and 0.0048), but were significantly recovered after the GSH administration (p = 0.0081 and 0.0263). The NOD mice exhibited disturbed hepatic tissue structure, which was attenuated by GSH. The GSH administration could also promote the production of GSH in the hepatocytes (p = 0.0264), and control the levels of inflammatory factors and oxidative stress related factors. These results indicate that GSH has significant effects on protecting against the hepatic injury during pSS, which may be associated with its regulation of the inflammatory factors and oxidative stress-related factors. This study suggests that GSH is a promising therapeutic strategy for controlling hepatic injury during pSS and offers valuable information for further research. PMID- 27186974 TI - Analysis of Image Gently Abdominal CT Protocol With the Use of Body Phantom Adapted to the Japanese Size. AB - OBJECTIVE: The purpose of this study was to analyze in detail the quality of abdominal CT images obtained using three protocols reported by Image Gently in 2014 (hereafter referred to as Image Gently 2014), with the use of a handmade body phantom adapted to typical body sizes of the Japanese population. Moreover, we converted the findings of Image Gently 2014 to match Japanese body sizes and referred to our converted findings as Image Gently Japan. MATERIALS AND METHODS: We scanned each phantom in a mechanical isocenter in accordance with the Image Gently 2014 abdominal imaging protocol. We changed the tube current-exposure time product per rotation from 25 to 250 mAs. The bowtie filter was set with a minimum FOV for the phantom size. We then analyzed the volume CT dose index (CTDIvol) measured CT number curve. We then used this CT number curve to calculate the CT number recommended by Image Gently Japan for each of the designated patient ages. RESULTS: The CTDIvol-measured CT number curve showed that, as the CTDIvol increased with each age, image noise decreased. When we assumed that the CTDIvol value for adults was 20 mGy, the measured CT number was 12.5 HU. We then multiplied each reduction coefficient by age (neonate and 1, 5, 10, and 15 years). The measured CT numbers for Image Gently Japan performed to attain limited dose reduction were 3.0, 3.9, 4.9, 6.0, and 9.0 HU, respectively, whereas those for Image Gently Japan performed to achieve moderate dose reduction were 3.3, 4.3, 5.3, 6.3, and 9.3 HU, respectively, and those for Image Gently Japan performed to attain aggressive dose reduction were 4.1, 5.1, 5.8, 6.8, and 9.5 HU, respectively. CONCLUSION: We analyzed the abdominal image quality demanded by Image Gently 2014, and we were able to adapt the results to the Japanese population and present them as our own Image Gently Japan recommendations. If the results of the present study become a foundation for scanning parameters for Japanese patients, we believe that they will eventually lead to a reduction in medical radiation exposure for this patient population. PMID- 27186976 TI - Using Dual Process Models to Examine Impulsivity Throughout Neural Maturation. AB - The multivariate construct of impulsivity is examined through neural systems and connections that comprise the executive functioning system. It is proposed that cognitive and behavioral components of impulsivity can be divided into two distinct groups, mediated by (1) the cognitive control system: deficits in top down cognitive control processes referred to as action/cognitive impulsivity and (2) the socioemotional system: related to bottom-up affective/motivational processes referred to as affective impulsivity. Examination of impulsivity from a developmental viewpoint can guide future research, potentially enabling the selection of more effective interventions for impulsive individuals, based on the cognitive components requiring improvement. PMID- 27186975 TI - The Time Course of Deafness and Retinal Degeneration in a Kunming Mouse Model for Usher Syndrome. AB - Usher syndrome is a group of autosomal recessive diseases characterized by congenital deafness and retinitis pigmentosa. In a mouse model for Usher syndrome, KMush/ush, discovered in our laboratory, we measured the phenotypes, characterized the architecture and morphology of the retina, and quantified the level of expression of pde6b and ush2a between postnatal (P) days 7, and 56. Electroretinograms and auditory brainstem response were used to measure visual and auditory phenotypes. Fundus photography and light microscopy were used to measure the architecture and morphology of the retina. Quantitative real-time PCR was used to measure the expression levels of mRNA. KMush/ush mice had low amplitudes and no obvious waveforms of Electroretinograms after P14 compared with controls. Thresholds of auditory brainstem response in our model were higher than those of controls after P14. By P21, the retinal vessels of KMush/ush mice were attenuated and their optic discs had a waxy pallor. The retinas of KMush/ush mice atrophied and the choroidal vessels were clearly visible. Notably, the architecture of each retinal layer was not different as compared with control mice at P7, while the outer nuclear layer (ONL) and other retinal layers of KMush/ush mice were attenuated significantly between P14 and P21. ONL cells were barely seen in KMush/ush mice at P56. As compared with control mice, the expression of pde6b and ush2a in KMush/ush mice declined significantly after P7. This study is a first step toward characterizing the progression of disease in our mouse model. Future studies using this model may provide insights about the etiology of the disease and the relationships between genotypes and phenotypes providing a valuable resource that could contribute to the foundation of knowledge necessary to develop therapies to prevent the retinal degeneration in patients with Usher Syndrome. PMID- 27186978 TI - Cell Type Preference of a Novel Human Derived Cell-Permeable Peptide dNP2 and TAT in Murine Splenic Immune Cells. AB - Cell-permeable peptides (CPPs) have been widely studied as an attractive drug delivery system to deliver therapeutic macromolecules such as DNA, RNA, and protein into cells. However, its clinical application is still limited and controversial due to the lack of a complete understanding of delivery efficiency in target cells. Previously we identified and characterized the novel and superior CPP, named dNP2, and here we comparatively analyzed intracellular delivery efficiency of dNP2 and TAT in various immune cells of mouse spleen to demonstrate their cell type preference. dNP2- or TAT-conjugated fluorescent proteins were most efficiently taken up by phagocytic cells such as dendritic cells and macrophages while little protein uptake was seen by lymphocytes including T cells, B cells, and NK cells. Interestingly CD8+ lymphoid dendritic cells and CD62LloCD44hi memory like T cell subsets showed significantly better uptake efficiency in vitro and in vivo relative to other dendritic cells or T cells, respectively. In addition, activated macrophages, T cells, and B cells took up the proteins more efficiently relative to when in the resting state. Importantly, only dNP2, not TAT, shows significant intracellular protein delivery efficiency in vivo. Collectively, this study provides important information regarding heterogeneous intracellular delivery efficiency of CPPs such as dNP2 and TAT with cell type preference in the spleen needed for its application in phagocytic cells or activated immune cells. PMID- 27186977 TI - TGF-beta Small Molecule Inhibitor SB431542 Reduces Rotator Cuff Muscle Fibrosis and Fatty Infiltration By Promoting Fibro/Adipogenic Progenitor Apoptosis. AB - Rotator cuff tears represent a large burden of muscle-tendon injuries in our aging population. While small tears can be repaired surgically with good outcomes, critical size tears are marked by muscle atrophy, fibrosis, and fatty infiltration, which can lead to failed repair, frequent re-injury, and chronic disability. Previous animal studies have indicated that Transforming Growth Factor-beta (TGF-beta) signaling may play an important role in the development of these muscle pathologies after injury. Here, we demonstrated that inhibition of TGF-beta1 signaling with the small molecule inhibitor SB431542 in a mouse model of massive rotator cuff tear results in decreased fibrosis, fatty infiltration, and muscle weight loss. These observed phenotypic changes were accompanied by decreased fibrotic, adipogenic, and atrophy-related gene expression in the injured muscle of mice treated with SB431542. We further demonstrated that treatment with SB431542 reduces the number of fibro/adipogenic progenitor (FAP) cells-an important cellular origin of rotator cuff muscle fibrosis and fatty infiltration, in injured muscle by promoting apoptosis of FAPs. Together, these data indicate that the TGF-beta pathway is a critical regulator of the degenerative muscle changes seen after massive rotator cuff tears. TGF-beta promotes rotator cuff muscle fibrosis and fatty infiltration by preventing FAP apoptosis. TGF-beta regulated FAP apoptosis may serve as an important target pathway in the future development of novel therapeutics to improve muscle outcomes following rotator cuff tear. PMID- 27186980 TI - Negative magnetoresistance without well-defined chirality in the Weyl semimetal TaP. AB - Weyl semimetals (WSMs) are topological quantum states wherein the electronic bands disperse linearly around pairs of nodes with fixed chirality, the Weyl points. In WSMs, nonorthogonal electric and magnetic fields induce an exotic phenomenon known as the chiral anomaly, resulting in an unconventional negative longitudinal magnetoresistance, the chiral-magnetic effect. However, it remains an open question to which extent this effect survives when chirality is not well defined. Here, we establish the detailed Fermi-surface topology of the recently identified WSM TaP via combined angle-resolved quantum-oscillation spectra and band-structure calculations. The Fermi surface forms banana-shaped electron and hole pockets surrounding pairs of Weyl points. Although this means that chirality is ill-defined in TaP, we observe a large negative longitudinal magnetoresistance. We show that the magnetoresistance can be affected by a magnetic field-induced inhomogeneous current distribution inside the sample. PMID- 27186979 TI - Positive Feedbacks Enhance Macroalgal Resilience on Degraded Coral Reefs. AB - Many reefs have shifted from coral and fish dominated habitats to less productive macroalgal dominated habitats, and current research is investigating means of reversing this phase shift. In the tropical Pacific, overfished reefs with inadequate herbivory can become dominated by the brown alga Sargassum polycystum. This alga suppresses recruitment and survival of corals and fishes, thus limiting the potential for reef recovery. Here we investigate the mechanisms that reinforce S. polycystum dominance and show that in addition to negatively affecting other species, this species acts in a self-reinforcing manner, positively promoting survival and growth of conspecifics. We found that survival and growth of both recruit-sized and mature S. polycystum fronds were higher within Sargassum beds than outside the beds and these results were found in both protected and fished reefs. Much of this benefit resulted from reduced herbivory within the Sargassum beds, but adult fronds also grew ~50% more within the beds even when herbivory did not appear to be occurring, suggesting some physiological advantage despite the intraspecific crowding. Thus via positive feedbacks, S. polycystum enhances its own growth and resistance to herbivores, facilitating its dominance (perhaps also expansion) and thus its resilience on degraded reefs. This may be a key feedback mechanism suppressing the recovery of coral communities in reefs dominated by macroalgal beds. PMID- 27186981 TI - Lack of Genotype and Phenotype Correlation in a Rice T-DNA Tagged Line Is Likely Caused by Introgression in the Seed Source. AB - Rice (Oryza sativa) is one of the most important crops in the world. Several rice insertional mutant libraries are publicly available for systematic analysis of gene functions. However, the tagging efficiency of these mutant resources-the relationship between genotype and phenotype-is very low. We used whole-genome sequencing to analyze a T-DNA-tagged transformant from the Taiwan Rice Insertional Mutants (TRIM) resource. The phenomics records for M0028590, one of the TRIM lines, revealed three phenotypes-wild type, large grains, and tillering dwarf-in the 12 T1 plants. Using the sequencing data for 7 plants from three generations of this specific line, we demonstrate that introgression from an indica rice variety might occur in one generation before the seed was used for callus generation and transformation of this line. In addition, the large-grain trait came from the GS3 gene of the introgressed region and the tillering dwarf phenotype came from a single nucleotide change in the D17 gene that occurred during the callus induction to regeneration of the transformant. As well, another regenerant showed completely heterozygous single-nucleotide polymorphisms across the whole genome. In addition to the known sequence changes such as T-DNA integration, single nucleotide polymorphism, insertion, deletion, chromosome rearrangement and doubling, spontaneous outcrossing occurred in the rice field may also explain some mutated traits in a tagged mutant population. Thus, the co segregation of an integration event and the phenotype should be checked when using these mutant populations. PMID- 27186982 TI - Synthesis of tetra- and octa-aurated heteroaryl complexes towards probing aromatic indoliums. AB - Polymetalated aromatic compounds are particularly challenging synthetic goals because of the limited thermodynamic stability of polyanionic species arising from strong electrostatic repulsion between adjacent carbanionic sites. Here we describe a facile synthesis of two polyaurated complexes including a tetra aurated indole and an octa-aurated benzodipyrrole. The imido trinuclear gold(I) moiety exhibits nucleophilicity and undergoes an intramolecular attack on a gold(I)-activated ethynyl to generate polyanionic heteroaryl species. Their computed magnetic properties reveal the aromatic character in the five-membered ring. The incorporation of the aurated substituents at the nitrogen atom can convert non-aromaticity in the parent indolium into aromaticity in the aurated one because of hyperconjugation. Thus, the concept of hyperconjugative aromaticity is extended to heterocycles with transition metal substituents. More importantly, further analysis indicates that the aurated substituents can perform better than traditional main-group substituents. This work highlights the difference in aromaticity between polymetalated aryls and their organic prototypes. PMID- 27186983 TI - Are There Spillover Effects from the GI Bill? The Mental Health of Wives of Korean War Veterans. AB - BACKGROUND: The Korean War GI Bill provided economic benefits for veterans, thereby potentially improving their health outcomes. However potential spillover effects on veteran wives have not been evaluated. METHODS: Data from wives of veterans eligible for the Korean War GI Bill (N = 128) and wives of non-veterans (N = 224) from the Health and Retirement Study were matched on race and coarsened birth year and childhood health using coarsened exact matching. Number of depressive symptoms in 2010 (average age = 78) were assessed using a modified, validated Center for Epidemiologic Studies-Depression Scale. Regression analyses were stratified into low (mother < 8 years schooling / missing data, N = 95) or high (mother >= 8 years schooling, N = 257) childhood socio-economic status (cSES) groups, and were adjusted for birth year and childhood health, as well as respondent's educational attainment in a subset of analyses. RESULTS: Husband's Korean War GI Bill eligibility did not predict depressive symptoms among veteran wives in pooled analysis or cSES stratified analyses; analyses in the low cSES subgroup were underpowered (N = 95, beta = -0.50, 95% Confidence Interval: ( 1.35, 0.35), p = 0.248, power = 0.28). CONCLUSIONS: We found no evidence of a relationship between husband's Korean War GI Bill eligibility and wives' mental health in these data, however there may be a true effect that our analysis was underpowered to detect. PMID- 27186985 TI - Fine-Tuning Ligand to Modulate the Magnetic Anisotropy in a Carboxylate-Bridged Dy2 Single-Molecule Magnet System. AB - A series of dinuclear Dy(III) compounds with the general formula [Dy2(MU2 anthc)4(anthc)2(L)2] (anthc(-) = 9-anthracenecarboxylate, L = 2,2'-bipyridyl (1), 1,10-phenanthroline (2), and 4,7-dimethyl-1,10-phenanthroline (3)) were synthesized and magnetically characterized. These compounds exhibit single molecule magnet (SMM) behavior in the absence of the direct-current field, which is rarely observed for carboxylate-bridged dinuclear Dy2 system. With the first coordination sphere of Dy(III) centers being fixed, the energy barrier was modulated by sequentially modifying the terminal neutral L ligands in this Dy2 system. Theoretical calculations revealed that the symmetry of the charge distribution surrounding the Dy(III) centers in 1-3 is the decisive factor to determine the relaxation of the SMMs. The combination of the larger charge distribution along the magnetic axis and lower charge distribution in the equatorial plane (hard plane) formed by five coplanar coordination atoms including two N atoms provided by an L ligand led to a strong easy-axis ligand field in these compounds. This work presents a rational method to modulate the dynamic magnetic relaxation of the lanthanide SMMs through fine-tuning electrostatic potential of the atoms on the hard plane. PMID- 27186984 TI - Transmission Dynamics of Zika Virus in Island Populations: A Modelling Analysis of the 2013-14 French Polynesia Outbreak. AB - Between October 2013 and April 2014, more than 30,000 cases of Zika virus (ZIKV) disease were estimated to have attended healthcare facilities in French Polynesia. ZIKV has also been reported in Africa and Asia, and in 2015 the virus spread to South America and the Caribbean. Infection with ZIKV has been associated with neurological complications including Guillain-Barre Syndrome (GBS) and microcephaly, which led the World Health Organization to declare a Public Health Emergency of International Concern in February 2015. To better understand the transmission dynamics of ZIKV, we used a mathematical model to examine the 2013-14 outbreak on the six major archipelagos of French Polynesia. Our median estimates for the basic reproduction number ranged from 2.6-4.8, with an estimated 11.5% (95% CI: 7.32-17.9%) of total infections reported. As a result, we estimated that 94% (95% CI: 91-97%) of the total population of the six archipelagos were infected during the outbreak. Based on the demography of French Polynesia, our results imply that if ZIKV infection provides complete protection against future infection, it would take 12-20 years before there are a sufficient number of susceptible individuals for ZIKV to re-emerge, which is on the same timescale as the circulation of dengue virus serotypes in the region. Our analysis suggests that ZIKV may exhibit similar dynamics to dengue virus in island populations, with transmission characterized by large, sporadic outbreaks with a high proportion of asymptomatic or unreported cases. PMID- 27186988 TI - GreA and GreB Enhance Expression of Escherichia coli RNA Polymerase Promoters in a Reconstituted Transcription-Translation System. AB - Cell-free environments are becoming viable alternatives for implementing biological networks in synthetic biology. The reconstituted cell-free expression system (PURE) allows characterization of genetic networks under defined conditions but its applicability to native bacterial promoters and endogenous genetic networks is limited due to the poor transcription rate of Escherichia coli RNA polymerase in this minimal system. We found that addition of transcription elongation factors GreA and GreB to the PURE system increased transcription rates of E. coli RNA polymerase from sigma factor 70 promoters up to 6-fold and enhanced the performance of a genetic network. Furthermore, we reconstituted activation of natural E. coli promoters controlling flagella biosynthesis by the transcriptional activator FlhDC and sigma factor 28. Addition of GreA/GreB to the PURE system allows efficient expression from natural and synthetic E. coli promoters and characterization of their regulation in minimal and defined reaction conditions, making the PURE system more broadly applicable to study genetic networks and bottom-up synthetic biology. PMID- 27186987 TI - Inferring RBP-Mediated Regulation in Lung Squamous Cell Carcinoma. AB - RNA-binding proteins (RBPs) play key roles in post-transcriptional regulation of mRNAs. Dysregulations in RBP-mediated mechanisms have been found to be associated with many steps of cancer initiation and progression. Despite this, previous studies of gene expression in cancer have ignored the effect of RBPs. To this end, we developed a lasso regression model that predicts gene expression in cancer by incorporating RBP-mediated regulation as well as the effects of other well-studied factors such as copy-number variation, DNA methylation, TFs and miRNAs. As a case study, we applied our model to Lung squamous cell carcinoma (LUSC) data as we found that there are several RBPs differentially expressed in LUSC. Including RBP-mediated regulatory effects in addition to the other features significantly increased the Spearman rank correlation between predicted and measured expression of held-out genes. Using a feature selection procedure that accounts for the adaptive search employed by lasso regularization, we identified the candidate regulators in LUSC. Remarkably, several of these candidate regulators are RBPs. Furthermore, majority of the candidate regulators have been previously found to be associated with lung cancer. To investigate the mechanisms that are controlled by these regulators, we predicted their target gene sets based on our model. We validated the target gene sets by comparing against experimentally verified targets. Our results suggest that the future studies of gene expression in cancer must consider the effect of RBP-mediated regulation. PMID- 27186989 TI - Spacers versus nebulizers in treatment of acute asthma - a prospective randomized study in preschool children. AB - OBJECTIVE: To compare administration of bronchodilators by nebulizers with delivery by metered dose inhalers (MDIs) with spacers and to evaluate the clinical effect of the treatment of acute asthma in preschool children. METHODS: A prospective randomized clinical trial in a pediatric emergency department (PED). Preschool children who were admitted for virus induced wheezing or acute asthma exacerbation were randomly allocated to receive bronchodilator treatment by nebulizer or by metered dose inhaler. The accompanying parents completed a questionnaire. RESULTS: The length of stay in the PED and the hospitalization rate were similar and no difference was seen in the parents' view of ease of use and device acceptance. Baseline data were similar for both groups apart from the family history of asthma and atopic disease that was greater in the nebulizer group. No significant differences were seen in heart rate, respiratory rate and oxygen saturation at baseline and after the treatment. According to the parents 40% of the participants had asthma diagnosis though up to 66% had some kind of asthma medication. CONCLUSIONS: Our data suggests that MDIs with spacers are at least as effective as nebulizers in the delivery of beta agonists to treat preschool children with virus induced wheezing or acute exacerbations of asthma in the PED. Parents may underestimate the gravity of their children's asthma. It is mandatory to provide adequate information to the staff and parents in order to treat pediatric acute asthma successfully. PMID- 27186990 TI - Nanoscale Skyrmions in a Nonchiral Metallic Multiferroic: Ni2MnGa. AB - Magnetic skyrmions belong to a set of topologically nontrivial spin textures at the nanoscale that have received increased attention due to their emergent behavior and novel potential spintronic applications. Discovering materials systems that can host skyrmions at room temperature in the absence of external magnetic field is of crucial importance not only from a fundamental aspect, but also from a technological point of view. So far, the observations of skyrmions in bulk metallic ferromagnets have been limited to low temperatures and to materials that exhibit strong chiral interactions. Here we show the formation of nanoscale skyrmions in a nonchiral multiferroic material, which is ferromagnetic and ferroelastic, Ni2MnGa at room temperature without the presence of external magnetic fields. By using Lorentz transmission electron microscopy in combination with micromagnetic simulations, we elucidate their formation, behavior, and stability under applied magnetic fields at room temperature. The formation of skyrmions in a multiferroic material with no broken inversion symmetry presents new exciting opportunities for the exploration of the fundamental physics of topologically nontrivial spin textures. PMID- 27186986 TI - Minimal Contribution of APOBEC3-Induced G-to-A Hypermutation to HIV-1 Recombination and Genetic Variation. AB - Although the predominant effect of host restriction APOBEC3 proteins on HIV-1 infection is to block viral replication, they might inadvertently increase retroviral genetic variation by inducing G-to-A hypermutation. Numerous studies have disagreed on the contribution of hypermutation to viral genetic diversity and evolution. Confounding factors contributing to the debate include the extent of lethal (stop codon) and sublethal hypermutation induced by different APOBEC3 proteins, the inability to distinguish between G-to-A mutations induced by APOBEC3 proteins and error-prone viral replication, the potential impact of hypermutation on the frequency of retroviral recombination, and the extent to which viral recombination occurs in vivo, which can reassort mutations in hypermutated genomes. Here, we determined the effects of hypermutation on the HIV 1 recombination rate and its contribution to genetic variation through recombination to generate progeny genomes containing portions of hypermutated genomes without lethal mutations. We found that hypermutation did not significantly affect the rate of recombination, and recombination between hypermutated and wild-type genomes only increased the viral mutation rate by 3.9 * 10-5 mutations/bp/replication cycle in heterozygous virions, which is similar to the HIV-1 mutation rate. Since copackaging of hypermutated and wild-type genomes occurs very rarely in vivo, recombination between hypermutated and wild type genomes does not significantly contribute to the genetic variation of replicating HIV-1. We also analyzed previously reported hypermutated sequences from infected patients and determined that the frequency of sublethal mutagenesis for A3G and A3F is negligible (4 * 10-21 and1 * 10-11, respectively) and its contribution to viral mutations is far below mutations generated during error prone reverse transcription. Taken together, we conclude that the contribution of APOBEC3-induced hypermutation to HIV-1 genetic variation is substantially lower than that from mutations during error-prone replication. PMID- 27186991 TI - Automatic detection of osteoporosis based on hybrid genetic swarm fuzzy classifier approaches. AB - OBJECTIVES: This study proposed a new automated screening system based on a hybrid genetic swarm fuzzy (GSF) classifier using digital dental panoramic radiographs to diagnose females with a low bone mineral density (BMD) or osteoporosis. METHODS: The geometrical attributes of both the mandibular cortical bone and trabecular bone were acquired using previously developed software. Designing an automated system for osteoporosis screening involved partitioning of the input attributes to generate an initial membership function (MF) and a rule set (RS), classification using a fuzzy inference system and optimization of the generated MF and RS using the genetic swarm algorithm. Fivefold cross-validation (5-FCV) was used to estimate the classification accuracy of the hybrid GSF classifier. The performance of the hybrid GSF classifier has been further compared with that of individual genetic algorithm and particle swarm optimization fuzzy classifiers. RESULTS: Proposed hybrid GSF classifier in identifying low BMD or osteoporosis at the lumbar spine and femoral neck BMD was evaluated. The sensitivity, specificity and accuracy of the hybrid GSF with optimized MF and RS in identifying females with a low BMD were 95.3%, 94.7% and 96.01%, respectively, at the lumbar spine and 99.1%, 98.4% and 98.9%, respectively, at the femoral neck BMD. The diagnostic performance of the proposed system with femoral neck BMD was 0.986 with a confidence interval of 0.942-0.998. The highest mean accuracy using 5-FCV was 97.9% with femoral neck BMD. CONCLUSIONS: The combination of high accuracy along with its interpretation ability makes this proposed automatic system using hybrid GSF classifier capable of identifying a large proportion of undetected low BMD or osteoporosis at its early stage. PMID- 27186992 TI - Water Determines the Structure and Dynamics of Proteins. AB - Water is an essential participant in the stability, structure, dynamics, and function of proteins and other biomolecules. Thermodynamically, changes in the aqueous environment affect the stability of biomolecules. Structurally, water participates chemically in the catalytic function of proteins and nucleic acids and physically in the collapse of the protein chain during folding through hydrophobic collapse and mediates binding through the hydrogen bond in complex formation. Water is a partner that slaves the dynamics of proteins, and water interaction with proteins affect their dynamics. Here we provide a review of the experimental and computational advances over the past decade in understanding the role of water in the dynamics, structure, and function of proteins. We focus on the combination of X-ray and neutron crystallography, NMR, terahertz spectroscopy, mass spectroscopy, thermodynamics, and computer simulations to reveal how water assist proteins in their function. The recent advances in computer simulations and the enhanced sensitivity of experimental tools promise major advances in the understanding of protein dynamics, and water surely will be a protagonist. PMID- 27186993 TI - Evaluation of the Toxicity and Antioxidant Activity of Redox Nanoparticles in Zebrafish (Danio rerio) Embryos. AB - Recently, we have been developing polymer and nanoparticle-based antioxidative nanotherapeutics. Our strategy is to eliminate overproduced reactive oxygen species (ROS), which are strongly related to various diseases. In order to facilitate the transition of the nanotherapeutics into clinical studies, we investigated the toxicity and antioxidant activity of our nanoparticles in a zebrafish model. In this study, zebrafish larvae were exposed to our highly ROS scavenging nanoparticle (RNP(O)), which was prepared using our original amphiphilic block copolymer, methoxy-poly(ethylene glycol)-b-poly[4-(2,2,6,6 tetramethylpiperidine-1-oxyl)oxymethylstyrene] (MeO-PEG-b-PMOT). When the larvae were exposed to 10-30 mM of low-molecular-weight (LMW) nitroxide radical (4 hydroxyl-2,2,6,6-tetramethylpiperidine-1-oxyl; TEMPOL), all were dead after 12 h, whereas no larva death was observed after exposure to RNP(O) at the same high concentrations. By staining mitochondria from the larvae, we found that LMW TEMPOL significantly induced mitochondrial dysfunction. In contrast, RNP(O) did not cause any significant reduction in the mitochondrial function of zebrafish larvae. It is important to reaffirm that RNP(O) treatment significantly enhanced survival of larvae treated with ROS inducers, confirming the antioxidant activity of RNP(O). Interestingly, RNP(O) exposure induced the expression of Nrf2 target gene (gstp1) in the larvae's intestines and livers. The results obtained in this study indicate that the antioxidative nanoparticle RNP(O) has great potential for clinical trials as it exhibits a potent therapeutic effect and extremely low toxicity to zebrafish embryos. PMID- 27186996 TI - [Surgical treatment of acute acromioclavicular dislocation. Preliminary report]. AB - INTRODUCTION: Determining what is the ideal acute management of type III lesions is controversial. The reconstruction of coracoclavicular ligaments is a fundamental part of the surgical management of these lesions. MATERIAL AND METHODS: The records of patients with acute acromioclavicular dislocation treated with open reduction and fixation with highly resistant sutures were reviewed. The preliminary results were assessed at the 3-month follow-up. RESULTS: Twelve patients were included, all of them males; mean age was 28 years. Three were Rockwood grade III, one grade IV, and 8 grade V. The mean time elapsed between the injury and the surgery was 9 days. According to the Constant scale 11 patients had excellent results and one had good results. Only one patient developed a seroma. Radiographic reduction was maintained in all patients. CONCLUSIONS: The anatomical reconstruction of coracoclavicular ligaments reduces complications considerably, especially when such reconstruction is made using materials with a grip strength similar to the one offered by native ligaments. PMID- 27186995 TI - Generation of the Methoxycarbonyl Radical by Visible-Light Photoredox Catalysis and Its Conjugate Addition with Electron-Deficient Olefins. AB - Visible-light photoredox-catalyzed fragmentation of methyl N-phthalimidoyl oxalate allows the direct construction of a 1,4-dicarbonyl structural motif by a conjugate addition of the methoxycarbonyl radical to reactive Michael acceptors. The regioselectivity of the addition of this alkoxyacyl radical species to electron-deficient olefins is heavily influenced by the electronic nature of the acceptor, behavior similar to that exhibited by nucleophilic alkyl radicals. PMID- 27186994 TI - Difference and Influence of Inactive and Active States of Cannabinoid Receptor Subtype CB2: From Conformation to Drug Discovery. AB - Cannabinoid receptor 2 (CB2), a G protein-coupled receptor (GPCR), is a promising target for the treatment of neuropathic pain, osteoporosis, immune system, cancer, and drug abuse. The lack of an experimental three-dimensional CB2 structure has hindered not only the development of studies of conformational differences between the inactive and active CB2 but also the rational discovery of novel functional compounds targeting CB2. In this work, we constructed models of both inactive and active CB2 by homology modeling. Then we conducted two comparative 100 ns molecular dynamics (MD) simulations on the two systems-the active CB2 bound with both the agonist and G protein and the inactive CB2 bound with inverse agonist-to analyze the conformational difference of CB2 proteins and the key residues involved in molecular recognition. Our results showed that the inactive CB2 and the inverse agonist remained stable during the MD simulation. However, during the MD simulations, we observed dynamical details about the breakdown of the "ionic lock" between R131(3.50) and D240(6.30) as well as the outward/inward movements of transmembrane domains of the active CB2 that bind with G proteins and agonist (TM5, TM6, and TM7). All of these results are congruent with the experimental data and recent reports. Moreover, our results indicate that W258(6.48) in TM6 and residues in TM4 (V164(4.56)-L169(4.61)) contribute greatly to the binding of the agonist on the basis of the binding energy decomposition, while residues S180-F183 in extracellular loop 2 (ECL2) may be of importance in recognition of the inverse agonist. Furthermore, pharmacophore modeling and virtual screening were carried out for the inactive and active CB2 models in parallel. Among all 10 hits, two compounds exhibited novel scaffolds and can be used as novel chemical probes for future studies of CB2. Importantly, our studies show that the hits obtained from the inactive CB2 model mainly act as inverse agonist(s) or neutral antagonist(s) at low concentration. Moreover, the hit from the active CB2 model also behaves as a neutral antagonist at low concentration. Our studies provide new insight leading to a better understanding of the structural and conformational differences between two states of CB2 and illuminate the effects of structure on virtual screening and drug design. PMID- 27186997 TI - [Treatment protocol in elderly patients with three- or four-fragment proximal humerus facture at a referral center located in an emerging economy]. AB - BACKGROUND: Proximal humerus fractures account for 4-5% of the fractures that occur among elderly people; they represent 45% of humerus fractures, and 13-16% of them are three- or four-fragment fractures. METHODS: Retrospective, observational, cross-sectional study of secondary data sources. The records of patients over 60 years of age with a diagnosis of three- or four-fragment proximal humerus fractures were analyzed. A non-probabilistic sampling technique of consecutive cases was used. The following variables were analyzed: age, sex, fragment number, limb involved and dominant limb, and treatment protocol. RESULTS: 118 patients were included, most of them females (83.9%), age range was 60-93 years, with a mean age of 73 years. Three-fragment fractures represented 63%, and four-fragment fractures 36%. The left limb was more frequently affected, accounting for 57%; 43% of cases were treated conservatively. Open reduction and internal fixation (ORIF) was performed in 39 cases with a tension band, in 22 patients with hemiarthroplasty, ORIF with a 4.5 T-plate in 5 patients, and ORIF with a LCP LISS plate in one patient. CONCLUSIONS: Female patients over 72 years of age underwent this kind of treatment more frequently. Surgical treatment accounted for 57%, unlike what the literature reports (20%). PMID- 27186998 TI - [Minimal invasive anterolateral ankle stabilization with a modified Hemi-Castaing technique]. AB - BACKGROUND: The lesions to the lateral ligaments of the ankle are a common sports related injury. There are multiple surgical technics to address the problem all with a common goal: achieve a proper stability of the ankle. The improvements in the minimal invasive technics as well as those in the materials to fixate bone tissue have also impacted the technics for lateral stabilization of the ankle. MATERIAL AND METHODS: We included all the patients with a diagnosis of lateral ankle instability which underwent surgery with a modify Hemi-Casting procedure with minimal invasive approach during the period between May 2004 and December 2007. We have an average follow-up of 30.3 months. RESULTS: Our patients presented a good outcome with an improvement in the Karlsson?s scale of 48.7 points (+/- 15.6) in the preoperative to 93.6 points (+/- 9.6) during follow-up. They returned to their sports activities after an average of 5.72 months (+/- 4.93). We used dynamic X-ray?s taken with the Telos system and achieved 81.9% of our patients presented an excellent and good personal satisfaction. CONCLUSIONS: The modifications to the Hemi-Castaing procedure to perform it with a minimal invasive technic are reproducible and provide us with another tool for the treatment of this pathology specially in the cases where there is no sufficient tissue to perform an anatomical repair. PMID- 27186999 TI - [Exposed distal radio-ulnar dislocation by dog bite. Reconstructive surgical technique using a soft tissue graft and a syndesmotic fixation implant. Case report]. AB - The main function of the forearm is the supination, which is achieved largely through the biomechanical characteristics and stability of the distal radio-ulnar joint. There are several surgical techniques for the treatment of distal radio ulnar dislocations isolated or associated with a fracture. We report the case of a canine trainer who was bitten at the wrist and distal forearm that came to the emergency department in where distal ulnar dislocation with muscle tendon exposure was diagnosed. Due to the offending agent and multiple soft tissue injuries the treatment with standard techniques was impossible. We describe the technique of treatment of this patient by placing autologous gracilis tendon graft, platelet rich plasma and two anchoring systems for ankle syndesmosis. Immobilization was maintained for six weeks with a subsequent rehabilitation and posterior valuation at 12, 18 and 28 weeks by the scale of MAYO, PRWE and DASH and finding a good result which implies the return to work and daily activities of the patient with minimal pain and limitation. PMID- 27187000 TI - [Total femoral replacement. Three case reports and literature review]. AB - INTRODUCTION: Currently hip and knee joint replacement were performed frequently at orthopedic centers. However, these surgeries do not last forever and thus revision procedures are required. The latter usually involve complications like bone loss that may compromise implant stability. METHODS: Three hip and knee arthroplasty revisions were performed from 2006 to 2011, which warranted the total replacement of the femur and the joints involved. The purpose of this paper is to describe our experience with these implants used in arthroplasty revision surgery. RESULTS: A standardized postoperative management protocol was used in all patients. They required debridement and specific antibiotic therapy. They had a significant improvement in the pain visual analog scale (VAS) (the score went from 8 to 2.3, p < 0.05) and in function, measured with the WOMAC score (from a preoperative score of 21.6 to 55, p < 0.05). CONCLUSIONS: Total femoral replacement is an infrequent, demanding and complex salvage surgery that represents an alternative to the disarticulation of the pelvic limb at the end stage of prosthetic disease. This is a feasible option used to improve patient functionality and decrease residual capacity for performing activities independently. PMID- 27187001 TI - [Spinal cord stimulation in teenager with complex regional pain syndrome for Lyme?s disease. Case report and review of the literature]. AB - Lyme disease is an emerging pathology in Mexico, producer of painful muscle skeletal either neurotic pain difficult to control. We present the case of a teenager girl who has complex regional pain type II of pelvic limb secondary to it, where it established a multidisciplinary management that finally was controlled with the placement of a spinal cord stimulator. We consider this as an unusual situation in an adolescent, as well as its evolution by 60 months where the literature only was reported in a few cases. PMID- 27187002 TI - [Relationship between angular deformity and primary osteoarthritis of the knee. Review article]. AB - BACKGROUND: Osteoarthritis of the knee is a common disease and angular deformities are usually associated to this degenerative affection. Secondary causes of angular deformities are well known in the scientific literature, but there are not many articles about the relationship between angular deformities and primary osteoarthritis. OBJECTIVE: To deepen in the relationship between angular deformities and primary osteoarthritis of the knee. METHOD: We conducted a literature review of a total of 300 articles in PubMed, Medline and Hinari locator information by EndNote, 52 of them were used and selected quotes to do the review, 47 of them in the last five years, including five books. DEVELOPMENT: A revision of important biochemical and biomechanics aspects were made in regards to the relationship between angular deformities and primary osteoarthritis of the knee. Causes of deformities according to the sagittal, coronal and rotational axis were taken into account. Factors related to deformities could be osseous or soft tissues of the knee joint. CONCLUSIONS: Deformities of the knee in patients suffering from primary osteoarthritis are common and there are osseous and soft tissues causes to justified the presence of these deformities. PMID- 27187003 TI - Quantifiable risk-benefit assessment of micronutrients: From theory to practice. AB - The EU Food Supplements Directive (2002/46/EC) mandates the determination of both maximum and minimum permitted levels (MPLs) for micronutrients. In order to determine MPLs which are feasible for particular population groups, a scientific approach should be used in which risk of high intake, risk of inadequacy and benefits are assessed in an integrated way taking all available data and severity and incidence of effect into account. In 2004, Renwick et al. (ILSI Europe) published a scientifically valid, flexible and pragmatic basis for a risk-benefit approach, which has been further developed here to make it a practical and quantifiable approach to be used by risk managers. The applicability of the approach is demonstrated using demo cases on iron and folate. The proposed approach has the capacity to utilize all relevant data available, including data from human studies, bioavailability data showing variability between specific forms of micronutrients and, in the case of animal studies, data on species comparability. The approach is therefore both practical and flexible, making it well suited to risk managers tasked with determining safe intake levels for micronutrients in different forms and for particular population groups. PMID- 27187004 TI - In-Phase Assembly of Slim DNA Lattices with Small Circular DNA Motifs via Short Connections of 11 and 16 Base Pairs. AB - Two kinds of stable motif were constructed: SAE (semi-crossover, antiparallel, even half-turns) tile from one small circular DNA molecule (42 or 64 nt) and two linear oligonucleotides; and DAE (double-crossover, antiparallel, even half turns) tile from one small circular DNA molecule (42 or 64 nt) and four linear oligonucleotides. With the SAE tiles, in-phase assembly of SAE-E (SAE tiles with even half-turns as connections (-E)) with the shortest -E of 11 base pairs (bp) generated homogeneous nanotubes with an average length of over 14 MUm and a diameter of 16-20 nm; with the DAE tiles, in-phase assembly of DAE-O (DAE tiles with odd half-turns as connections (-O)) with the shortest -O of 16 bp produced slim monolayer nanoyarns (25-30 nm wide), nanoscarfs (100-300 nm wide), and nanoribbons (~100 nm wide). Interestingly, a phenomenon we term "knitting nanoyarns" into nanoscarfs was observed. Finally a curvature mechanism according to the ring rotation directions is suggested to explain the formation of nanotubes, wavy nanoyarns, nanoscarfs, and nanoribbons. PMID- 27187005 TI - Calcineurin in a Crowded World. AB - Calcineurin is a Ser/Thr phosphatase that is important for key biological processes, including immune system activation. We previously identified a region in the intrinsically disordered regulatory domain of calcineurin that forms a critical amphipathic alpha-helix (the "distal helix") that is required for complete activation of calcineurin. This distal helix was shown to have a Tm close to that of human body temperature. Because the Tm was determined in dilute buffer, we hypothesized that other factors inherent to a cellular environment might modulate the stability of the distal helix. One such factor that contributes to stability in other proteins is macromolecular crowding. The cell cytoplasm is comprised of up to 400 g/L protein, lipids, nucleic acids, and other compounds. We hypothesize that the presence of such crowders could increase the thermal stability of the distal helix and thus lead to a more robust activation of calcineurin in vivo. Using biophysical and biochemical approaches, we show that the distal helix of calcineurin is indeed stabilized when crowded by the synthetic polymers dextran 70 and ficoll 70, and that this stabilization of the distal helix increases the activity of calcineurin. PMID- 27187007 TI - A Monoclonal Antibody That Discriminates Between SNAP-Tagged and CLIP-Tagged Proteins. AB - SNAP-tag technology allows recombinant proteins to be covalently labeled to O(6) benzylguanine (BG)-modified substrates with 1:1 stoichiometry. By attaching according fluorophores, this method is ideally suited for in vitro and in vivo imaging, as well as protein interaction analyses. Fluorophores modified with BG react with the SNAP-tag, whereas those modified with O(2)-benzylcytosine (BC) conjugate to a more recent derivative known as the CLIP-tag. The orthogonal substrate specificity of the SNAP- and CLIP-tags extends the range of applications by allowing double labeling. We previously developed a monoclonal antibody (mAb) that recognizes both tags. In this study, we describe a new mAb, which is specific for the SNAP-tag alone. Therefore, this mAb allows discrimination between SNAP- and CLIP-tags within a broad range of immunological methods, including enzyme-linked immunosorbent assays, western blotting, flow cytometry, and immunohistochemistry. PMID- 27187008 TI - Misoprostol versus ergometrine-oxytocin for preventing postpartum haemorrhage: a systematic review and meta-analysis of randomized controlled trials. AB - OBJECTIVE: To compare the effects of misoprostol versus ergometrine-oxytocin for postpartum haemorrhage (PPH) prevention, and provide important evidence to choose optimal agents for preventing PPH in developing countries. METHODS: The Cochrane Central Register of Controlled Trials, PubMed, EMbase, and ClinicalTrails.gov were searched from inception to 1st January 2016. Two authors independently extracted data and assessed risk of bias of studies according to Cochrane Handbook5.1.0. Meta-analysis was performed using RevMan5.2.4 software. RESULTS: A total of 4034 women from six randomized controlled trials (RCTs) were included. Meta-analyses showed that the PPH rate (7.6% vs. 4.2%, RR = 1.81, 95%CI (1.40, 2.35), P < 0.01), and the additional uterotonic therapy (19.2% vs. 10.5%, RR = 1.83, 95%CI (1.57, 2.14), P < 0.01) for misoprostol group were significantly higher than ergometrine-oxytocin group, respectively. But there was no significant difference of severe PPH rate between two groups (1.2% vs. 0.76%, RR = 1.55, 95%CI (0.78, 3.07), P = 0.21). The need for manual removal of placenta in misoprostol was only about one-third of ergometrine-oxytocin (0.5% vs. 1.4%, RR = 0.33, 95%CI (0.15, 0.76), P < 0.01). CONCLUSIONS: Misoprostol can be used in the third stage of labor for preventing PPH where sterilized syringe and trained midwife were absent, and ergoetrine-oxytocin could be deemed as alternative agent in low-resource setting due to recognized effect. As a result of limited evidence about these uterotonic agents, the more high-quality RCTs are needed to determine the potentials and harms of various uterotonic agents for preventing PPH in developing countries. PMID- 27187009 TI - Effects of walking on body composition in perimenopausal and postmenopausal women: a systematic review and meta-analysis. AB - OBJECTIVE: The aim of the study was to conduct a systematic review and meta analysis of randomized controlled trials that examined the effect of walking on body weight, body mass index (BMI), and body fat percentage in perimenopausal and postmenopausal women. METHODS: Two authors identified randomized controlled trials of interventions at least 4 weeks in duration that included at least one group with walking as the only treatment and a no-exercise control group. Participants were inactive at baseline. Weighted mean differences were calculated using the fixed-effects and random-effects models. Heterogeneity among trials was examined using the Q statistic and I methods. Potential publication bias was assessed through funnel plot inspection. RESULTS: Eight studies met the study inclusion criteria. Meta-analysis results showed statistically significant reductions in mean differences for BMI (-0.33 kg/m, 95% CI -0.62 to -0.04 kg/m), body weight (-1.14 kg, 95% CI -1.86 to -0.42 kg), and body fat percentage ( 2.36%, 95% CI -3.21% to -1.52%). The results were consistent in showing effects of walking on BMI (I = 11%), body weight (I = 20%), and body fat percentage (I = 0%). Funnel plots showed asymmetry for body composition. CONCLUSIONS: Walking interventions improved body composition in perimenopausal and postmenopausal women, which underscores the central role of walking as a physical activity for health promotion. PMID- 27187010 TI - Menopausal women requesting egg/embryo donation: examining health screening guidelines for assisted reproductive technology. AB - OBJECTIVE: As more postreproductive women opt to pursue pregnancy with advanced assisted reproductive technologies (ART), the menopausal practitioner will become more involved in counseling, screening, and referral of premenopausal, perimenopausal, and postmenopausal women for these services. This review was conducted with the aim of (1) evaluating ART screening practices as they pertain to postreproductive women, and (2) reviewing the outcomes of ART using oocyte donation in postreproductive women. METHODS: A total of 950 unique records were found on PubMed, Clinical Key, and Google Scholar. Of these, 252 records were screened for relevance based on their titles and abstracts. With further review of these 252 records, 93 full-text articles were assessed for eligibility, and 63 were excluded based on relevance to our study. Finally, 30 studies were included in our qualitative synthesis. RESULTS: Despite the increasing use of ART in postreproductive women, there are limited guidelines for determining candidacy with regard to maternal health, the most comprehensive of which are the guidelines from the American Society for Reproductive Medicine (ASRM). Although the American Society for Reproductive Medicine guidelines state that healthy women over 50 who are prepared for parenthood are candidates for ART through oocyte donation, they note that older women should be counseled as to the increased obstetric risk associated with advanced maternal age. With aging, particularly for those women who are menopausal and postmenopausal, the woman and her fetus, however, are at risk of increased morbidity and mortality as compared with younger, healthy pregnant women. Because national trends suggest that women are delaying childbearing, the cohort of postreproductive women looking toward ART using donor oocytes as a fertility option will expand and menopausal practitioners will often participate in the ART counseling of these women. CONCLUSIONS: Because maternal and fetal morbidity and mortality increase in postmenopausal women who become pregnant through ART, practitioners caring for this cohort should provide input into developing standardized, comprehensive guidelines for this population so that screening is consistent for all older women seeking this intervention and risks are objectively outlined and considered. PMID- 27187012 TI - The response to ospemifene in normal human breast tissue cultures. PMID- 27187017 TI - Computational model-informed design and bioprinting of cell-patterned constructs for bone tissue engineering. AB - Three-dimensional (3D) bioprinting is a rapidly advancing tissue engineering technology that holds great promise for the regeneration of several tissues, including bone. However, to generate a successful 3D bone tissue engineering construct, additional complexities should be taken into account such as nutrient and oxygen delivery, which is often insufficient after implantation in large bone defects. We propose that a well-designed tissue engineering construct, that is, an implant with a specific spatial pattern of cells in a matrix, will improve the healing outcome. By using a computational model of bone regeneration we show that particular cell patterns in tissue engineering constructs are able to enhance bone regeneration compared to uniform ones. We successfully bioprinted one of the most promising cell-gradient patterns by using cell-laden hydrogels with varying cell densities and observed a high cell viability for three days following the bioprinting process. In summary, we present a novel strategy for the biofabrication of bone tissue engineering constructs by designing cell-gradient patterns based on a computational model of bone regeneration, and successfully bioprinting the chosen design. This integrated approach may increase the success rate of implanted tissue engineering constructs for critical size bone defects and also can find a wider application in the biofabrication of other types of tissue engineering constructs. PMID- 27187011 TI - Estrogen therapy may counterbalance eutrophic remodeling of coronary arteries and increase bradykinin relaxation in a rat model of menopausal hypertension. AB - OBJECTIVE: Hypertension causes adverse remodeling and vasomotor alterations in coronaries. Hormones such as estrogen may help counterbalance some of these effects. The aim of this study was to analyze the effects of ovariectomy and estrogen therapy in a rat model of menopausal hypertension induced by angiotensin II (AII). METHODS: We investigated diameter, tone, and mechanics of intramural coronaries taken from ovariectomized female rats (n = 11) that received chronic AII treatment to induce hypertension, and compared the results with those found in female rats that were also given estrogen therapy (n = 11). The "hypertensive control" group (n = 11) underwent an abdominal sham operation, and received AII. After 4 weeks of AII treatment, side branches of left anterior descendent coronary (approximately 200 MUm in diameter) were isolated, cannulated with plastic microcannulas at both ends, and studied in vitro in a vessel chamber. The inner and outer diameter of the arteries were measured by microangiometry, and spontenuous tone, wall thickness, wall cross-sectional area, tangential stress, incremental distensibility, circumferential incremental elastic modulus, thromboxane agonist-induced tone, and bradykinin-induced dilation were calculated. RESULTS: In hypertension, intramural small coronaries show inward eutrophic remodeling after ovariectomy comparing with hypertensive controls. Estrogen therapy had an opposite effect on vessel diameter. Hormone therapy led to an increase in spontaneous tone, allowing for greater dilatative capacity. CONCLUSIONS: Estrogen may therefore be considered to counterbalance some of the adverse changes seen in the wall of intramural coronaries in the early stages of chronic hypertension. PMID- 27187018 TI - In-vitro and in-vivo evaluation of the anticancer activity of diruthenium-2, a new trithiolato arene ruthenium complex [(eta6-p-MeC6H4Pri)2Ru2(MU-S-p C6H4OH)3]Cl. AB - In the present study, we investigated the anticancer action of the trithiolato arene ruthenium complex, [(eta-p-MeC6H4Pr)2Ru2(MU-S-p-C6H4OH)3]Cl, named diruthenium-2, both in vitro and in vivo. The mechanism of antiproliferative, cytotoxic, and DNA-damaging activity, and the effect on expressions of cell cycle regulatory proteins were investigated using a WST-1-based proliferation assay, lactate dehydrogenase leakage assay, comet assay, flow cytometry, and western blot analysis. In-vivo anticancer activity was evaluated using Ehrlich tumor bearing NMRI mice. Diruthenium-2 inhibited the growth of all cancer cell lines used, the most sensitive being gastric (AGS), breast cancer (BT-549, MCF-7, MDA MB-231), and leukemic (HL-60, MOLT-4) cells. In MCF-7 cells, it caused a G1/S cell cycle arrest, along with an increase in the expression of protein p21 and cyclin B1. We also observed increased levels of MRN complex proteins, which, together with the results from the comet assay, indicate the formation of DNA double-strand breaks. In tumor-bearing mice, diruthenium-2 at doses of 3 and 5 mg/kg inhibits the growth of solid Ehrlich tumor, although weaker than cisplatin. However, it did not prolong the post-therapeutic survival. Our results suggest the in-vitro potential of diruthenium-2 should be further evaluated in studies using other in-vivo models. PMID- 27187020 TI - Parental Grief Following the Death of a Child from Cancer: The Ongoing Odyssey. AB - BACKGROUND: The death of a child is a devastating event that results in profound grief and significant psychosocial and physical morbidities in parents. The parental grief journey is a complex phenomenon necessitating the utilization of newer models of bereavement with a focus on relationships and exploration of parents' perceived meanings of the experience. OBJECTIVES: To further characterize the grief journey of parents whose child died from cancer in order to better identify parents who can benefit from additional bereavement support and design strategies to improve bereavement services for these parents. DESIGN: We conducted focus group sessions with 11 bereaved parents. The parents were given two prompts to describe their grief journey before and after their child's death, and their responses in a narrative form were audio-recorded. The responses were coded and studied independently by semantic content analysis. RESULTS: Collation and analysis of the coded responses to both prompts results in the emergence of four concepts from the parental narratives: (1) description of the grief trajectory and evolution of grief over time, (2) mechanisms of parental coping throughout the grief journey, (3) factors that exacerbate parental grief, and (4) sources of parental support throughout the grief journey. CONCLUSIONS: The narratives highlighted that parents whose child died of cancer experience a unique and evolving form of grief and they wish to continue their bond with the deceased child. We recommend that healthcare providers and institutions incorporate support systems into a comprehensive bereavement program for families of children who die from cancer. PMID- 27187019 TI - Suppressive effects on cell proliferation and motility in gastric cancer SGC-7901 cells by introducing ulinastatin in vitro. AB - Ulinastatin (UTI) is a kind of urinary trypsin inhibitor regulating broad spectrum proteases and is used widely in the treatment of inflammatory diseases. Some evidence has suggested that UTI has antitumor functions in human carcinomas, but its function in gastric cancer (GC) has not been discussed extensively. In this study, we investigated the effects of UTI on GC SGC-7901 cells in vitro by preincubating cells with the UTI. The expression of the related molecules, urokinase-type plasminogen activator (uPA), was investigated at both the mRNA and the protein stages. Activation of uPA was analyzed and the phosphorylation of ERK1/2 downstream uPA was detected. According to the results, UTI downregulated uPA expression and significantly suppressed the activation of uPA and the phosphorylation of ERK1/2. Furthermore, the SGC-7901 cells treated by UTI showed a significant decrease in cell proliferation and impairment of invasion and migration. However, no significant influence was observed on cell apoptosis. By ectopically expressing uPA in SGC-7901 cells, suppression effects of UTI were rescued. We suggest that UTI suppresses GC cell proliferation, motility, and at least partly conducted through uPA. Although the effects of UTI in GC cells need to be validated further, UTI represents a strong therapeutic strategy that is worth following up in GC treatment. PMID- 27187021 TI - Reverse engineering genius: historiometric studies of superlative talent. AB - Although genius has been defined in the dictionary as requiring an IQ above 140, this definition depends on an arbitrary methodological decision made by Lewis Terman for his longitudinal study of more than 1500 intellectually gifted children, a study that occupies four of the five volumes of Genetic Studies of Genius. Yet, only the second volume, by Catharine Cox, studied bona fide geniuses, by applying historiometric methods to 301 highly eminent creators and leaders. After defining historiometric research, I examine the difference between historical genius and intellectual giftedness with respect to heterogeneous intellects, personality differences, and early development and show that the actual relation between IQ and genius is small and heavily contingent on domain specific assessment, the operation of traits like persistence and openness to experience, and the impact of diversifying experiences, including both developmental adversity and subclinical psychopathology. Hence, the dictionary definition of "genius" has minimal, if any, justification. If, using historiometric methods, one works backward from recognized geniuses, such as those studied by Cox, one might not obtain the kind of sample that Terman obtained for his longitudinal study. The two methods produce two distinct subgroups of the larger population. PMID- 27187006 TI - Targeting vascular (endothelial) dysfunction. AB - : Cardiovascular diseases are major contributors to global deaths and disability adjusted life years, with hypertension a significant risk factor for all causes of death. The endothelium that lines the inner wall of the vasculature regulates essential haemostatic functions, such as vascular tone, circulation of blood cells, inflammation and platelet activity. Endothelial dysfunction is an early predictor of atherosclerosis and future cardiovascular events. We review the prognostic value of obtaining measurements of endothelial function, the clinical techniques for its determination, the mechanisms leading to endothelial dysfunction and the therapeutic treatment of endothelial dysfunction. Since vascular oxidative stress and inflammation are major determinants of endothelial function, we have also addressed current antioxidant and anti-inflammatory therapies. In the light of recent data that dispute the prognostic value of endothelial function in healthy human cohorts, we also discuss alternative diagnostic parameters such as vascular stiffness index and intima/media thickness ratio. We also suggest that assessing vascular function, including that of smooth muscle and even perivascular adipose tissue, may be an appropriate parameter for clinical investigations. LINKED ARTICLES: This article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc. PMID- 27187028 TI - Health utility of patients with Crohn's disease and ulcerative colitis: a systematic review and meta-analysis. AB - INTRODUCTION: The aim of this systematic review was to collect and summarize the current data on the utilities of patients with Crohn's disease (CD) and ulcerative colitis (UC). AREAS COVERED: A meta-analysis of the obtained utilities was performed using a random-effects model and meta-regression by the disease type and severity. A bootstrap analysis was performed as it does not require assumption on distribution of the data. The highest utility among patients with CD and UC was observed when the diseases were in remission. The meta-regression analysis showed that both disease severity and an instrument/method/questionnaire used to obtain utilities were significant predictors of utility. Utility was the lowest for severe disease and the highest for disease in remission, the association was more notable in patients with CD compared with UC. Expert commentary: The issue of patients' utility is important for healthcare decision makers but it has not been fully investigated and requires further study. PMID- 27187027 TI - Psychiatric and substance use disorders in HIV/hepatitis C virus (HCV)-coinfected patients: does HCV clearance matter? [Agence Nationale de Recherche sur le SIDA et les Hepatites Virales (ANRS) HEPAVIH CO13 cohort]. AB - OBJECTIVES: The objective of this nested study was to assess the prevalence of psychiatric disorders in a sample of HIV/hepatitis C virus (HCV)-coinfected patients according to their HCV status. METHODS: The nested cross-sectional study, untitled HEPAVIH-Psy survey, was performed in a subset of HIV/HCV coinfected patients enrolled in the French Agence Nationale de Recherche sur le SIDA et les Hepatites Virales (ANRS) CO13 HEPAVIH cohort. Psychiatric disorders were screened for using the Mini International Neuropsychiatric Interview (MINI 5.0.0). RESULTS: Among the 286 patients enrolled in the study, 68 (24%) had never received HCV treatment, 87 (30%) were treatment nonresponders, 44 (15%) were currently being treated and 87 (30%) had a sustained virological response (SVR). Of the 286 patients enrolled, 121 patients (42%) screened positive for a psychiatric disorder other than suicidality and alcohol/drug abuse/dependence, 40 (14%) screened positive for alcohol abuse/dependence, 50 (18%) screened positive for drug abuse/dependence, 50 (17.5%) were receiving an antidepressant treatment and 69 (24%) were receiving an anxiolytic. Patients with an SVR did not significantly differ from the other groups in terms of psychiatric disorders. Patients receiving HCV treatment screened positive less often for an anxiety disorder. The highest rate of drug dependence/abuse was among HCV treatment-naive patients. CONCLUSIONS: Psychiatric disorders were frequent in HIV/HCV-coinfected patients and their rates were comparable between groups, even for patients achieving an SVR. Our results emphasize the need for continuous assessment and care of coinfected patients, even after HCV clearance. Drug addiction remains an obstacle to access to HCV treatment. Despite the recent advent and continued development of directly acting antiviral agents (DAAs), it is still crucial to offer screening and comprehensive care for psychiatric and addictive disorders. PMID- 27187029 TI - GLOBAL PATTERNS OF LEPTOSPIRA PREVALENCE IN VERTEBRATE RESERVOIR HOSTS. AB - Leptospirosis is a widespread emerging bacterial zoonosis. As the transmission is believed to be predominantly waterborne, human incidence is expected to increase in conjunction with global climate change and associated extreme weather events. Providing more accurate predictions of human leptospirosis requires more detailed information on animal reservoirs that are the source of human infection. We evaluated the prevalence of Leptospira in vertebrates worldwide and its association with taxonomy, geographic region, host biology, ambient temperature, and precipitation patterns. A multivariate regression analysis with a meta analysis-like approach was used to analyze compiled data extracted from 300 Leptospira-related peer reviewed papers. A fairly uniform Leptospira infection prevalence of about 15% was found in the majority of mammalian families. Higher prevalence was frequently associated with species occupying urban habitats, and this may explain why climatic factors were not significantly correlated with prevalence as consistently as expected. Across different approaches of the multiple regression analyses, the variables most frequently correlated with Leptospira infection prevalence were the host's ability to swim, minimum ambient temperature, and methodologic quality of the study. Prevalence in carnivores was not associated with any climatic variable, and the importance of environmental risk factors were indicated to be of lesser consequence in nonhuman mammals. The dataset is made available for further analysis. PMID- 27187030 TI - MORTALITY DURING TREATMENT: FACTORS AFFECTING THE SURVIVAL OF OILED, REHABILITATED COMMON MURRES (URIA AALGE). AB - After major oil spills, hundreds to thousands of live stranded birds enter rehabilitative care. To target aspects of rehabilitative efforts for improvement and to evaluate which initial physical examination and biomedical parameters most effectively predict survival to release, medical records were examined from 913 Common Murres ( Uria aalge ; COMUs) oiled during the November 2001-January 2003 oil spill associated with the sunken S.S. Jacob Luckenbach off San Francisco, California, US. Results showed that 52% of all deaths occurred during the first 2 days of treatment. Birds stranding closest to the wreck had greater amounts of oil on their bodies than birds stranding farther away. More heavily oiled birds were in better clinical condition than birds with lesser amounts of oil, as shown by higher body mass (BM), packed cell volumes (PCV), total plasma protein (TP), and higher survival proportions. Additionally, BM, PCV, TP, and body temperature were positively correlated. For comparison, medical records from all nonoiled COMUs admitted for rehabilitation at the same facility during 2007-09 (n=468) were examined, and these variables were also found to be positively correlated. Oiled birds with BM under 750 g had approximately 5% lower PCV than BM-matched nonoiled COMUs. More heavily oiled COMUs may be in better condition than less oiled birds because heavily oiled birds must beach themselves immediately to avoid drowning and hypothermia, whereas lightly oiled birds may postpone beaching until exhausted due to extreme body catabolism. The strong relationship of PCV to BM regardless of oiling provides evidence that anemia commonly encountered in oiled seabirds may be a sequela to overall loss of body condition rather than solely due to toxic effects of oiling. Clinical information garnered in this study provides guidance for triage decisions during oil spills. PMID- 27187031 TI - WIND TURBINES CAUSE CHRONIC STRESS IN BADGERS (MELES MELES) IN GREAT BRITAIN. AB - A paucity of data exists with which to assess the effects of wind turbines noise on terrestrial wildlife, despite growing concern about the impact of infrasound from wind farms on human health and well-being. In 2013, we assessed whether the presence of turbines in Great Britain impacted the stress levels of badgers ( Meles meles ) in nearby setts. Hair cortisol levels were used to determine if the badgers were physiologically stressed. Hair of badgers living <1 km from a wind farm had a 264% higher cortisol level than badgers >10 km from a wind farm. This demonstrates that affected badgers suffer from enhanced hypothalamo-pituitary adrenal activity and are physiologically stressed. No differences were found between the cortisol levels of badgers living near wind farms operational since 2009 and 2012, indicating that the animals do not become habituated to turbine disturbance. Cortisol levels in the affected badgers did not vary in relation to the distance from turbines within 1 km, wind farm annual power output, or number of turbines. We suggest that the higher cortisol levels in affected badgers is caused by the turbines' sound and that these high levels may affect badgers' immune systems, which could result in increased risk of infection and disease in the badger population. PMID- 27187032 TI - EFFECT OF STORAGE TIME AND STORAGE CONDITIONS ON ANTIBODY DETECTION IN BLOOD SAMPLES COLLECTED ON FILTER PAPER. AB - Using filter paper to collect blood from wildlife for antibody analysis can be a powerful technique to simplify the collection, transport, and storage of blood samples. Despite these advantages, there are limited data that detail how long these samples can be stored and how storage conditions affect antibody longevity. We used blood samples collected on filter paper from coyotes experimentally infected with Yersinia pestis to determine optimum sample storage conditions over time. Blood samples collected on filter paper were stored for 454 d or more in four groups: 1) at ambient temperature and at ambient relative humidity, 2) at ambient temperature with desiccant, 3) at 4 C with desiccant, and 4) at -20 C with desiccant. Samples stored at 4 C or -20 C with desiccant had detectable antibody for a longer period of time than the samples stored at room temperature. PMID- 27187033 TI - ECOLOGIC DRIVERS AND POPULATION IMPACTS OF AVIAN TRICHOMONOSIS MORTALITY EVENTS IN BAND-TAILED PIGEONS (PATAGIOENAS FASCIATA) IN CALIFORNIA, USA. AB - : Avian trichomonosis, a disease typically caused by the protozoan parasite Trichomonas gallinae , is a well recognized cause of death in many avian species. In California, US, trichomonosis has caused periodic epidemics in Pacific Coast Band-tailed Pigeons ( Patagioenas fasciata monilis). We summarize reported mortality events and investigate ecologic drivers and population impacts associated with epidemic mortality due to trichomonosis in Band-tailed Pigeons. Between 1945 and 2014, 59 mortality events involving Band-tailed Pigeons were reported in California with the number of reported events increasing over time. Estimated mortality for these events was variable, ranging between 10 and 10,000 pigeons. Events were most-frequently reported in Monterey (19%; 11/59) and San Luis Obispo (8%; 5/59) counties. Events often started in January (32%; 9/28) and February (50%; 14/28) and lasted 5-68 d. Impacts of mortality events on pigeon populations were indicated by Breeding Bird Survey and Christmas Bird Count abundance indices, which showed a decline in outbreak years compared to nonoutbreak years. Environmental conditions most associated with outbreak years included higher average temperatures between January and March, the period most associated with mortality events, and lower average precipitation in December just prior to mortality events. In Monterey County, events tended to occur in winters following higher acorn production of coast live oaks ( Quercus agrifolia ) in the fall. Weather and food abundance could be related to increased transmission or enhanced viability of Trichomonas spp. Although estimated mortality due to avian trichomonosis was highly variable across years, cumulative losses were substantial and likely to have a negative impact on population size. PMID- 27187034 TI - MORTALITY OF SELECTED AVIAN ORDERS SUBMITTED TO A WILDLIFE DIAGNOSTIC LABORATORY (SOUTHEASTERN COOPERATIVE WILDLIFE DISEASE STUDY, USA): A 36-YEAR RETROSPECTIVE ANALYSIS. AB - To determine the relative importance of mortality factors for birds and to assess for patterns in avian mortality over time, we retrospectively examined data of birds submitted to the Southeastern Cooperative Wildlife Disease Study (SCWDS; http://vet.uga.edu/scwds ), US, from 1976 to 2012. During this period, SCWDS, a wildlife diagnostic laboratory, received 2,583 wild bird specimens, from the taxonomic orders Apodiformes, Caprimulgiformes, Cuculiformes, Passeriformes, and Piciformes, originating from 22 states. Data from 2,001 of these birds were analyzed using log-linear models to explore correlations between causes of mortality, taxonomic family, demography, geographic location, and seasonality. Toxicosis was the major cause of mortality, followed by trauma, bacterial infection, physiologic stress, viral infection, and other (mortality causes with low sample numbers and etiologies inconsistent with established categories). Birds submitted during fall and winter had a higher frequency of parasitic infections, trauma, and toxicoses, whereas birds submitted during the spring and summer were more likely to die of an infectious disease, physiologic stress, or trauma. We noted a decrease in toxicoses concurrent with an increase in bacterial infections and trauma diagnoses after the mid-1990s. Toxicosis was the most commonly diagnosed cause of death among adult birds; the majority of juveniles died from physiologic stress, trauma, or viral infections. Infectious agents were diagnosed more often within the families Cardinalidae and Fringilidae, whereas noninfectious etiologies were the primary diagnoses in the Bombycillidae, Parulidae, Sturnidae, Turdidae, and Icteridae. There are important inherent limitations in the examination of data from diagnostic labs, as submission of cases varies in timing, frequency, location, and species and is often influenced by several factors, including media coverage of high-profile mortality events. Notwithstanding, our data provide a rare opportunity to examine long-term, regional, and temporal patterns in causes of avian mortality, and they allow for the analysis of novel and rare mortality factors. PMID- 27187035 TI - Volumetric measurements of the inner ear in patients with Meniere's disease using three-dimensional magnetic resonance imaging. AB - CONCLUSION: This study described the lateralities of axial length of inner ear (ALIE), of the volume of inner ear (VIE) and age-related differences of the volume of inner ear components in patients with chronic rhinosinusitis (CRS). Age related differences were found in ALIE and the positive correlation in ALIE and the volume of the cochlea (VC) of the affected ear in patients with Meniere's disease (MD). OBJECTIVE: To identify side or sex-related differences in the ALIE, the length of the spiral canal of cochlea (LSCC), and the volume of components of the inner ear in MD and CRS. METHODS: Thirty-two with unilateral MD and 14 with CRS were included. Images were acquired with a 3.0-tesla unit using SPACE sequences. The ALIE was measured and the VIE, VC, the volume of the vestibule (VV), and of the semi-circular canals (VSC) were also measured. RESULTS: In CRS, ALIE of the right ear in males was significantly longer than in females. Patients younger than 60 years old with CRS had a significantly larger VIE, VC, and VSC than older than 60. In MD, the ALIE in older than 60 was longer than below 60. PMID- 27187036 TI - Physician predictions of length of stay of patients admitted with heart failure. AB - Physicians' ability to predict length of stay is understudied, particularly for patients with heart failure (HF) admissions. The objective of this prospective, observational cohort study was to measure the accuracy of inpatient physicians' predictions of length of stay at the time of admission of patients admitted to an academic tertiary care hospital with HF and to determine whether level of experience improves accuracy. The patients included 165 adults consecutively admitted with heart failure, about whom 415 predictions were made within 24 hours of admission. Mean and median lengths of stay were 10.9 and 8 days, respectively. The mean difference between predicted and actual length of stay was statistically significant for all groups: interns, -5.9 days (95% confidence interval [CI]: 8.2 to -3.6, P < 0.0001); residents, -4.3 days (95% CI: -6.0 to -2.7, P = 0.0001); attending cardiologists, -3.5 days (95% CI: -5.1 to -2.0, P < 0.0001). There were no differences in accuracy by level of experience (P = 0.61). Physicians, regardless of experience, underestimate length of stay of patients admitted with HF. Journal of Hospital Medicine 2016;11:642-645. (c) 2016 Society of Hospital Medicine. PMID- 27187037 TI - Effect of Simvastatin, Coenzyme Q10, Resveratrol, Acetylcysteine and Acetylcarnitine on Mitochondrial Respiration. AB - Some therapeutic and/or adverse effects of drugs may be related to their effects on mitochondrial function. The effects of simvastatin, resveratrol, coenzyme Q10, acetylcysteine, and acetylcarnitine on Complex I-, Complex II-, or Complex IV linked respiratory rate were determined in isolated brain mitochondria. The protective effects of these biologically active compounds on the calcium-induced decrease of the respiratory rate were also studied. We observed a significant inhibitory effect of simvastatin on mitochondrial respiration (IC50 = 24.0 MUM for Complex I-linked respiration, IC50 = 31.3 MUM for Complex II-linked respiration, and IC50 = 42.9 MUM for Complex IV-linked respiration); the inhibitory effect of resveratrol was found at very high concentrations (IC50 = 162 MUM for Complex I-linked respiration, IC50 = 564 MUM for Complex II-linked respiration, and IC50 = 1454 MUM for Complex IV-linked respiration). Concentrations required for effective simvastatin- or resveratrol-induced inhibition of mitochondrial respiration were found much higher than concentrations achieved under standard dosing of these drugs. Acetylcysteine and acetylcarnitine did not affect the oxygen consumption rate of mitochondria. Coenzyme Q10 induced an increase of Complex I-linked respiration. The increase of free calcium ions induced partial inhibition of the Complex I+II-linked mitochondrial respiration, and all tested drugs counteracted this inhibition. None of the tested drugs showed mitochondrial toxicity (characterized by respiratory rate inhibition) at drug concentrations achieved at therapeutic drug intake. Resveratrol, simvastatin, and acetylcarnitine had the greatest neuroprotective potential (characterized by protective effects against calcium induced reduction of the respiratory rate). PMID- 27187038 TI - Novel CDKL5 Mutations in Czech Patients with Phenotypes of Atypical Rett Syndrome and Early-Onset Epileptic Encephalopathy. AB - The X-linked CDKL5 gene, which encodes cyclin-dependent kinase-like 5 protein, has been implicated in early-onset encephalopathy and atypical Rett syndrome with early-onset seizures. The CDKL5 protein is a kinase required for neuronal development and morphogenesis, but its precise functions are still largely unexplored. Individuals with CDKL5 mutations present with severe global developmental delay, intractable epilepsy, and Rett-like features. A clear genotype-phenotype correlation has not been established due to an insufficient number of reported cases. The aim of this study was to analyse the CDKL5 gene in Czech patients with early-onset seizures and Rett-like features. We performed mutation screening in a cohort of 83 individuals using high-resolution melting analysis, DNA sequencing and multiplex ligation- dependent probe amplification. Molecular analyses revealed heterozygous pathogenic mutations in three girls with severe intellectual disability and intractable epilepsy starting at the age of two months. All three identified mutations, c.637G>A, c.902_977+29del105, and c.1757_1758delCT, are novel, thus significantly extending the growing spectrum of known pathogenic CDKL5 sequence variants. Our results support the importance of genetic testing of the CDKL5 gene in patients with early-onset epileptic encephalopathy and Rett-like features with early-onset seizures. This is the first study referring to molecular defects of CDKL5 in Czech cases. PMID- 27187040 TI - X-Chromosome Inactivation Analysis in Different Cell Types and Induced Pluripotent Stem Cells Elucidates the Disease Mechanism in a Rare Case of Mucopolysaccharidosis Type II in a Female. AB - Mucopolysaccharidosis type II (MPS II) is an X-linked lysosomal storage disorder resulting from deficiency of iduronate-2-sulphatase activity. The disease manifests almost exclusively in males; only 16 symptomatic heterozygote girls have been reported so far. We describe the results of X-chromosome inactivation analysis in a 5-year-old girl with clinically severe disease and heterozygous mutation p.Arg468Gln in the IDS gene. X inactivation analysed at three X chromosome loci showed extreme skewing (96/4 to 99/1) in two patient's cell types. This finding correlated with exclusive expression of the mutated allele. Induced pluripotent stem cells (iPSC) generated from the patient's peripheral blood demonstrated characteristic pluripotency markers, deficiency of enzyme activity, and mutation in the IDS gene. These cells were capable of differentiation into other cell types (cardiomyocytes, neurons). In MPS II iPSC clones, the X inactivation ratio remained highly skewed in culture conditions that led to partial X inactivation reset in Fabry disease iPSC clones. Our data, in accordance with the literature, suggest that extremely skewed X inactivation favouring the mutated allele is a crucial condition for manifestation of MPS II in females. This suggests that the X inactivation status and enzyme activity have a prognostic value and should be used to evaluate MPS II in females. For the first time, we show generation of iPSC from a symptomatic MPS II female patient that can serve as a cellular model for further research of the pathogenesis and treatment of this disease. PMID- 27187041 TI - Intracellular Delivery of Synthetic dsRNA to Leukemic Cells Induces Apoptotic and Necrotic Cell Death. AB - The type of tumour cell death dictates the type of adaptive immune response mounted against the tumours. In haematological malignancies such as acute myeloid leukaemia (AML), immune evasion due to the poor immunogenicity of leukemic cells is a major hurdle in generating an effective immune response. Transfection of synthetic dsRNA, poly I:C, into leukemic cells to trigger tumour cell death and enhance immunogenicity of the tumour is a promising immunotherapeutic approach. However, the temporal cell death kinetics of poly I:C-electroporated AML cells has not been thoroughly investigated. Electroporation of U937 cells, a human AML cell line, with a high dose of poly I:C resulted in cytotoxicity as early as 1 h post-transfection. Flow cytometric analysis revealed the temporal switch from early apoptosis to late apoptosis/secondary necrosis in poly I:C-electroporated cells in which the nuclear morphology at later time points was consistent with necrotic cell death. Our brief findings demonstrated the temporal cell death kinetics of dsRNA-transfected leukemic cells. This finding is an important development in the field of dsRNA immunotherapy for leukaemia as understanding the type of cell death elicited by transfected dsRNA will dictate the type of immune response to be directed against leukemic cells. PMID- 27187039 TI - TIMP4 Modulates ER-alpha Signalling in MCF7 Breast Cancer Cells. AB - Tissue inhibitor of metalloprotease 4 (TIMP4) contributes to poor prognosis in breast and other tumours. However, the mechanisms of how TIMP4 influences breast cancer cell behaviour are unknown. Our aim was to explore the signalling pathways modulated by TIMP4 in breast cancer cells. Human recombinant TIMP4 was added to MCF7 breast cancer cells and RNASeq was performed. TIMP4 RNASeq results were validated by RT-PCR. Network analyses of TIMP4-exposed cells showed that ER alpha, HIF1A and TGF-beta signalling were activated, whereas FOXO3 signalling was downregulated. ER-alpha protein levels were increased and concordantly, promoters of TIMP4-upregulated genes were significantly enriched in oestrogen-binding sites. We concluded that TIMP4 modulates multiple signalling pathways relevant in cancer in MCF7 cells, including the ER-alpha cascade. PMID- 27187042 TI - IgE anti-Haemophilus influenzae type b (Hib) antibodies detected in serum of Hib vaccinated asthmatic and non-asthmatic pediatric patients. AB - BACKGROUND: Haemophilus influenzae type b (Hib) bacterium causes severe illness in infants and children, but has largely been eliminated by introducing a universal Hib conjugate vaccine. While effects of certain vaccinations on atopic disease have been studied, little is known about the relationship between Hib vaccination and diseases of altered immunoglobulin E (IgE) regulation (asthma or atopy). As such, it is necessary to provide more evidence concerning Hib vaccination as a possible risk factor for atopic disease. METHODS: Total serum IgE and IgE-and IgG-anti-Hib antibody responses were studied in Hib vaccinated asthmatic (N.=14) and non-asthmatic children (N=26) (VaccZymeTM Human Anti Hib Enzyme Immunoassay Kit). Data are reported as mean optical density (OD) values. RESULTS: We found that: 1) total serum IgE levels were higher in asthmatic compared with non-asthmatic subjects (389+/-125 vs. 125+/-129, P<0.001); 2) IgE and IgG anti-Hib antibody responses were similar in both asthmatic and non asthmatic subjects (0.722+/-0.279 and 0.681+/-0.280, respectively; P=0.65; 0.450+/-0.505 and 0.573+/-0.779, respectively; P=0.580). CONCLUSIONS: The universal Hib vaccine antigen did not result in either increased IgE, or IgG anti Hib antibody responses in asthmatic or non-asthmatics subjects. Thus, in this cohort, no association between Hib vaccination and asthma status was identified. PMID- 27187043 TI - DNA Strand Replacement Mechanism in Molecular Beacons Encoded for the Detection of Cancer Biomarkers. AB - Signaling properties of a fluorescent hairpin oligonucleotide molecular beacon (MB) encoded to recognize protein survivin (Sur) mRNA have been investigated. The process of complementary target binding to SurMB with 20-mer loop sequence is spontaneous, as expected, and characterized by a high affinity constant (K = 2.51 * 10(16) M(-1)). However, the slow kinetics at room temperature makes it highly irreversible. To understand the intricacies of target binding to MB, a detailed kinetic study has been performed to determine the rate constants and activation energy Ea for the reaction at physiological temperature (37 degrees C). Special attention has been paid to assess the value of Ea in view of reports of negative activation enthalpy for some nucleic acid reactions that would make the target binding even slower at increasing temperatures in a non-Arrhenius process. The target-binding rate constant determined is k = 3.99 * 10(3) M(-1) s(-1) at 37 degrees C with Ea = 28.7 +/- 2.3 kcal/mol (120.2 +/- 9.6 kJ/mol) for the temperature range of 23 to 55 degrees C. The positive high value of Ea is consistent with a kinetically controlled classical Arrhenius process. We hypothesize that the likely contribution to the activation energy barrier comes from the SurMB stem melting (tm = 53.7 +/- 0.2 degrees C), which is a necessary step in the completion of target strand hybridization with the SurMB loop. A low limit of detection (LOD = 2 nM) for target tDNA has been achieved. Small effects of conformational polymorphs of SurMB have been observed on melting curves. Although these polymorphs could potentially cause a negative Ea, their effect on kinetic transients for target binding is negligible. No toehold preceding steps in the mechanism of target binding were identified. PMID- 27187045 TI - Three-Dimensional CAIPIRINHA SPACE TSE for 5-Minute High-Resolution MRI of the Knee. AB - OBJECTIVE: The aim of this study was to prospectively test the hypothesis that a 2-dimensional (2D) CAIPIRINHA (controlled aliasing in parallel imaging results in higher acceleration) sampling pattern facilitates 5-minute high spatial resolution 3-dimensional (3D) sampling perfection with application optimized contrast using different flip angle evolutions (SPACE) magnetic resonance imaging (MRI) of the knee with image quality similar or better than current 2D turbo spin echo (TSE) and 3D SPACE standards. MATERIALS AND METHODS: The study was approved by our institutional review board. Twenty asymptomatic subjects (12 men, 8 women; mean age, 42 years; age range, 24-65 years) underwent 3 T MRI of the knee. A 4 fold accelerated 3D SPACE TSE prototype with 2D CAIPIRINHA sampling pattern and 5 minute acquisition time was compared with commercially available 2-fold and 4 fold accelerated 3D SPACE and 2D TSE pulse sequences with acquisition times of 11 minutes and 15 seconds, 6 minutes and 30 seconds, as well as 9 minutes and 48 seconds, respectively. Outcome variables included image quality, anatomic visibility, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR). Statistical analysis included Friedman, repeated measures analysis of variances, and Cohen's weighted kappa tests. Bonferroni-corrected P values of 0.005 and less were considered statistically significant. RESULTS: Overall, image quality, visibility of anatomic structures, SNR, and CNR of 3D CAIPIRINHA SPACE were statistically similar to 2-fold accelerated 3D SPACE and significantly better than 4-fold accelerated 3D SPACE, which exhibited degrading parallel imaging artifacts. Compared with 2.5-mm 2D TSE images, 0.5-mm 3D CAIPIRINHA SPACE images showed statistically similar good edge sharpness and very good contrast resolution, and significantly less partial volume as well as absent chemical shift and pulsatile flow artifacts. Visibility of menisci, anterior cruciate ligament, posterior cruciate ligament, medial collateral ligament, and lateral collateral ligament was good to very good on 0.5-mm 3D CAIPIRINHA SPACE images as compared with good on 2.5-mm 2D TSE image (P < 0.005). The SNR of fat, fluid, and cartilage as well as CNR between cartilage, fluid, fat, posterior cruciate ligament, and menisci were minimally higher on 2.5-mm 2D TSE image (P < 0.005). Image quality, visibility of anatomic structures, SNR, and CNR of 2.5-mm 3D CAIPIRINHA SPACE and 2.5-mm 2D TSE images were good to very good without significant differences. CONCLUSIONS: Three-dimensional SPACE with 2D CAIPIRINHA sampling pattern enables high-quality 3D TSE MRI of the knee at an acquisition time of 5 minutes and image quality, visibility of anatomic structures, SNR, and CNR similar to conventional 3D SPACE and 2D TSE, both of which require approximately 10-minute acquisition times. PMID- 27187047 TI - Effects of closure versus non-closure of the visceral and parietal peritoneum at cesarean section: does it have any effect on postoperative vital signs? A prospective randomized study. AB - OBJECTIVE: To investigate the effect of peritonization at cesarean section on postoperative vital signs which was thought to be an indirect finding secondary to increased sympathetic activity originated from pain caused by stretched peritoneum. METHODS: One hundred and thirty-three pregnant women were randomized to four groups; Closure of parietal peritoneum only (group 1; n = 32), closure of visceral and parietal peritoneums (group 2; n = 32), no closure of peritoneums (group 3; n = 32) and closure of the visceral peritoneum only (group 4; n = 32). All participants were monitored for blood pressure, pulse activity and hourly urinary output during the first postoperative 24 h. Postoperative pain was measured using a Visual Analogue Scale 6th and 24th hours after surgery. Return of bowel function was measured from the end of the operation to the first passage of flatus. Operating time, pre- and postoperative hemoglobin, postoperative complications, length of hospital stay and postoperative urine osmolarity were noted. RESULTS: The mean surgery duration was significantly longer in group 2. Diuresis was found significantly decreased in group 2. Pulse rate and systolic and diastolic blood pressure were significantly higher in group 2. Closure of both peritoneums was associated with higher post-operative pain as assessed using Visual analogue scale score analyses in group 2. CONCLUSION: Both visceral and parietal membrane closure in cesarean section should be avoided in women with hypertensive disorders, renal function abnormalities and autonomic dysfunction because of increased postoperative pain and associated sympathetic overactivity. PMID- 27187046 TI - Dual-Energy Computed Tomography Angiography of the Head and Neck With Single Source Computed Tomography: A New Technical (Split Filter) Approach for Bone Removal. AB - OBJECTIVES: Dual-energy computed tomographic angiography (DE-CTA) has been demonstrated to improve the visualization of the head and neck vessels. The aim of this study was to test the potential of split-filter single-source dual-energy CT to automatically remove bone from the final CTA data set. MATERIALS AND METHODS: Dual-energy CTA was performed in 50 consecutive patients to evaluate the supra-aortic arteries, either to grade carotid artery stenosis or to rule out traumatic dissections. Dual-energy CTA was performed on a 128-slice single-source CT system equipped with a special filter array to separate the 120-kV spectrum into a high- and a low-energy spectrum for DE-based automated bone removal. Image quality of fully automated bone suppression and subsequent manual optimization was evaluated by 2 radiologists on maximum intensity projections using a 4-grade scoring system. The effect of image reconstruction with an iterative metal artifact reduction algorithm on DE postprocessing was tested using a 3-grade scoring system, and the time demand for each postprocessing step was measured. RESULTS: Two patients were excluded due to insufficient arterial contrast enhancement; in the remaining 48 patients, automated bone removal could be performed successfully. The addition of iterative metal artifact reduction algorithm improved image quality in 58.3% of the cases. After manual optimization, DE-CTA image quality was rated excellent in 7, good in 29, and moderate in 10 patients. Interobserver agreement was high (kappa = 0.85). Stenosis grading was not influenced using DE-CTA with bone removal as compared with the original CTA. The time demand for DE image reconstruction was significantly higher than for single-energy reconstruction (42.1 vs 20.9 seconds). CONCLUSIONS: Our results suggest that bone removal in DE-CTA of the head and neck vessels with a single-source CT is feasible and can be performed within acceptable time and moderate user interaction. PMID- 27187048 TI - Intricate Functions of Matrix Metalloproteinases in Physiological and Pathological Conditions. AB - Matrix metalloproteinases (MMPs) are a diverse group of proteolytic enzymes and play an important role in the degradation and remodeling of the extracellular matrix (ECM). In normal physiological conditions, MMPs are usually minimally expressed. Despite their low expression, MMPs have been implicated in many cellular processes ranging from embryological development to apoptosis. The activity of MMPs is controlled at three different stages: (1) transcription; (2) zymogen activation; and (3) inhibition of active forms by tissue inhibitor metalloproteinases (TIMPs). They can collectively degrade any component of ECM and basement membrane, and their excessive activity has been linked to numerous pathologies mainly including, but not limited to, tumor invasion and metastasis. The lack of information about several MMPs and the steady stream of new discoveries suggest that there is much more to be studied in this field. In particular, there is a need for controlling their expression in disease states. Various studies over the past 30 years have found that each MMP has a specific mode of activation, action, and inhibition. Drugs specifically targeting individual MMPs could revolutionize the treatment of a great number of health conditions and tremendously reduce their burden. In this review article, we have summarized the recent advances in understanding the role of MMPs in physiological and pathological conditions. J. Cell. Physiol. 231: 2599-2621, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27187049 TI - Validation of a plant-wide phosphorus modelling approach with minerals precipitation in a full-scale WWTP. AB - The focus of modelling in wastewater treatment is shifting from single unit to plant-wide scale. Plant-wide modelling approaches provide opportunities to study the dynamics and interactions of different transformations in water and sludge streams. Towards developing more general and robust simulation tools applicable to a broad range of wastewater engineering problems, this paper evaluates a plant wide model built with sub-models from the Benchmark Simulation Model No. 2-P (BSM2-P) with an improved/expanded physico-chemical framework (PCF). The PCF includes a simple and validated equilibrium approach describing ion speciation and ion pairing with kinetic multiple minerals precipitation. Model performance is evaluated against data sets from a full-scale wastewater treatment plant, assessing capability to describe water and sludge lines across the treatment process under steady-state operation. With default rate kinetic and stoichiometric parameters, a good general agreement is observed between the full scale datasets and the simulated results under steady-state conditions. Simulation results show differences between measured and modelled phosphorus as little as 4-15% (relative) throughout the entire plant. Dynamic influent profiles were generated using a calibrated influent generator and were used to study the effect of long-term influent dynamics on plant performance. Model-based analysis shows that minerals precipitation strongly influences composition in the anaerobic digesters, but also impacts on nutrient loading across the entire plant. A forecasted implementation of nutrient recovery by struvite crystallization (model scenario only), reduced the phosphorus content in the treatment plant influent (via centrate recycling) considerably and thus decreased phosphorus in the treated outflow by up to 43%. Overall, the evaluated plant-wide model is able to jointly describe the physico-chemical and biological processes, and is advocated for future use as a tool for design, performance evaluation and optimization of whole wastewater treatment plants. PMID- 27187050 TI - Sulfur-based denitrification: Effect of biofilm development on denitrification fluxes. AB - Elemental sulfur (S(o)) can serve as an electron donor for denitrification. However, the mechanisms and rates of S(o)-based denitrification, which depend on a biofilm development on a solid S(o) surface, are not well understood. We used completely-mixed reactors packed with S(o) chips to systematically explore the behavior of S(o)-based denitrification as a function of the bulk nitrate (NO3(-)) concentration and biofilm development. High-purity (99.5%) and agricultural-grade (90% purity) S(o) chips were tested to explore differences in performance. NO3(-) fluxes followed a Monod-type relationship with the bulk NO3(-) concentration. For high-purity S(o), the maximum NO3(-) flux increased from 0.4 gN/m(2)-d at 21 days to 0.9 g N/m(2)-d at around 100 days, but then decreased to 0.65 gN/m(2)-d at 161 days. The apparent (extant) half-saturation constant for NO3(-) KSapp, based on the bulk NO3(-) concentration and NO3(-) fluxes into the biofilm, increased from 0.1 mgN/L at 21 days to 0.8 mgN/L at 161 days, reflecting the increasing mass transfer resistance as the biofilm thickness increased. Nitrite (NO2(-)) accumulation became significant at bulk NO3(-) concentration above 0.2 mgN/L. The behavior of the agricultural-grade S(o) was very similar to the high-purity S(o). The kinetic behavior of S(o)-based denitrification was consistent with substrate counter-diffusion, where the soluble sulfur species diffuse from the S(o) particle into the base of the biofilm, while NO3(-) diffuses into the biofilm from the bulk. Initially, the fluxes were low due to biomass limitation (thin biofilms). As the biofilm thickness increased with time, the fluxes first increased, stabilized, and then decreased. The decrease was probably due to increasing diffusional resistance in the thick biofilm. Results suggest that fluxes comparable to heterotrophic biofilm processes can be achieved, but careful management of biofilm accumulation is important to maintain high fluxes. PMID- 27187051 TI - Assisted reproductive technology and perinatal outcomes: conventional versus discordant-sibling design. AB - OBJECTIVE: To compare risks of adverse perinatal outcomes between assisted reproductive technology (ART) and naturally conceived singleton births using a dual design approach. DESIGN: Discordant-sibling and conventional cross-sectional general population comparison. SETTING: Not applicable. PATIENT(S): All singleton live births, conceived naturally or via ART. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Birth weight, gestational age, low birth weight, preterm delivery, small for gestational age (SGA), low Apgar score. RESULT(S): A total of 32,762 (0.8%) of 3,896,242 singleton live births in the three states were conceived via ART. In 6,458 sibling pairs, ART-conceived singletons were 33 g lighter (adjusted beta = -33.40, 95% confidence interval [CI], -48.60, -18.21) and born half a day sooner (beta = -0.58, 95% CI, -1.02, -0.14) than singletons conceived naturally. The absolute risk of low birth weight and preterm birth was 6.8% and 9.7%, respectively, in the ART group and 4.9% and 7.9%, respectively, in the non-ART group. The odds of low birth weight were 33% higher (adjusted odds ratio [aOR] = 1.33; 95% CI, 1.13, 1.56) and 20% higher for preterm birth (aOR = 1.20; 95% CI, 1.07, 1.34). The odds of SGA and low Apgar score were not significantly different in both groups (aOR = 1.22; 95% CI, 0.88, 1.68; and aOR = 0.75; 95% CI, 0.54, 1.05, respectively). Results of conventional analyses were similar, although the magnitude of risk was higher for preterm birth (aOR, 1.51; 95% CI 1.46, 1.56). CONCLUSION(S): Despite some inflated risks in the general population comparison, ART remained associated with an increased likelihood of low birth weight and preterm birth when underlying maternal factors were kept constant using discordant-sibling comparison. PMID- 27187052 TI - The application of absolute quantitative (1)H NMR spectroscopy in drug discovery and development. AB - INTRODUCTION: The identification of a drug candidate and its structural determination is the most important step in the process of the drug discovery and for this, nuclear magnetic resonance (NMR) is one of the most selective analytical techniques. AREA COVERED: The present review illustrates the various perspectives of absolute quantitative (1)H NMR spectroscopy in drug discovery and development. It deals with the fundamentals of quantitative NMR (qNMR), the physiochemical properties affecting qNMR, and the latest referencing techniques used for quantification. The precise application of qNMR during various stages of drug discovery and development, namely natural product research, drug quantitation in dosage forms, drug metabolism studies, impurity profiling and solubility measurements is elaborated. To achieve this, the authors explore the literature of NMR in drug discovery and development between 1963 and 2015. It also takes into account several other reviews on the subject. EXPERT OPINION: qNMR experiments are used for drug discovery and development processes as it is a non-destructive, versatile and robust technique with high intra and interpersonal variability. However, there are several limitations also. qNMR of complex biological samples is incorporated with peak overlap and a low limit of quantification and this can be overcome by using hyphenated chromatographic techniques in addition to NMR. PMID- 27187053 TI - Influence of Complex Loading Conditions on Intervertebral Disc Failure. AB - STUDY DESIGN: High resolution imaging investigation of the failure of ovine lumbar intervertebral discs under complex loading. OBJECTIVE: To investigate how different loading combinations influence the mechanism and extent of intervertebral disc failure. SUMMARY OF BACKGROUND DATA: Even though there has been extensive research on how an intervertebral disc fails under various conditions, failure mechanisms remain unclear. In addition, the influence of different loading directions on the mode and extent of failure under complex loading was never systematically investigated. METHODS: Thirty ovine lumbar spinal segments were loaded in a newly developed, dynamic, 6-degree-of-freedom (6 DOF) disc loading simulator under five combinations of the following loading parameters: 0 degrees -13 degrees flexion, 0 degrees -10 degrees lateral bending, 0 degrees -4 degrees axial rotation, 0-800 N axial compression. A total of 1000 cycles at 2 Hz were done. After testing, imaging of the discs was performed in an ultra-high field magnetic resonance imaging (11.7 T) scanner and with a micro-computed tomography scanner. RESULTS: A total of 13 large endplate junction failures (EPJFs) occurred, of which all but one maintained an intact cartilaginous endplate. Ten out of 13 EPJFs occurred caudally. Four solely annulus failures occurred affecting only the outer posterior annulus. A herniation was not observed. The maximum moments measured in any group (median) were 52.5 N . m flexion, 16.5 N . m lateral bending, and 14.0 N . m axial rotation. CONCLUSION: Complex loading protocols could lead to EPJFs (76%) and annulus failures (24%) in vitro. The combination of flexion, lateral bending, axial rotation, and axial compression bears the highest risk for caudal EPJF. Flexion without lateral bending and vice versa has the lowest risk for failure. Both axial compression and axial rotation seem to have a smaller influence than flexion and lateral bending. It seems that a herniation requires an additional failure of the cartilaginous endplate, likely initiated by further axial compressive load. LEVEL OF EVIDENCE: 4. PMID- 27187054 TI - Maternal total T4 during the first half of pregnancy: physiologic aspects and the risk of adverse outcomes in comparison with free T4. AB - AIM: We aimed to investigate TT4 physiological aspects and associations with clinical end-points. BACKGROUND: Total T4 (TT4) has been suggested as a marker for maternal thyroid function during pregnancy because as compared to FT4 (i) TT4 measurement is not affected by binding protein interference, (ii) TT4 is considered to be more stable from the second trimester onwards, and (iii) TT4 better reflects changes in the hypothalamic-pituitary-thyroid axis. However, this is based on data from small studies, and, more importantly, it is unknown whether TT4 is associated with adverse pregnancy or child outcomes. METHODS: We selected 5647 mother-child pairs from a large population-based prospective cohort with data on maternal TSH, FT4 and TT4 during early pregnancy (median 13.2 weeks, 95% range 9.8-17.6). We used multivariable (non)linear and logistic regression models to study the association of maternal TT4 with pre-eclampsia, premature delivery, birthweight and offspring IQ and compare the results with previously obtained results for FT4. RESULTS: The change of mean TT4 levels was 27.5% compared to 20.2% for FT4. There was a log-linear association of TT4 and FT4 with TSH, but the explained variability of TSH was much lower for TT4 than for FT4 (R-squared TT4: 2.5% vs 8.0% for FT4). In contrast to FT4, there was no independent association of maternal TT4 with pre-eclampsia, premature delivery, birthweight or offspring IQ. CONCLUSION: Maternal TT4 levels are highly variable in the first half of pregnancy and are poorly related to maternal TSH. This study shows that maternal TT4 levels are either not associated, or not better associated as compared to FT4, with adverse pregnancy or child outcomes. This suggests that the maternal TT4 is inferior to FT4 in the assessment of maternal thyroid function during the first half of pregnancy. PMID- 27187055 TI - Inactivation of indicator organisms in wastewater treated by a high rate algal pond system. AB - AIMS: High rate algal ponds (HRAPs) have been suggested as replacements for waste stabilization ponds (WSPs) in Community Wastewater Management Systems (CWMS) used in rural South Australian (SA) towns. Treated effluent from CWMS is reused for irrigation. To manage the risk of human exposure to pathogens, the disinfection performance of HRAPs was validated using the common indicators Escherichia coli and F-RNA bacteriophage; aerobic spore-forming bacteria (ASFB) were used as indicators for protozoa. METHODS AND RESULTS: Using standard culture methods, the removal of the indicator organisms F-RNA bacteriophage, E. coli and ASFB by a HRAP at Kingston-on-Murray, SA, was measured. The mean log10 reduction values achieved for the F-RNA bacteriophage was 1.59 +/- 0.82 log10 PFU 100 ml(-1) and for E. coli it was 2.13 +/- 0.55 log10 E. coli MPN 100 ml(-1) . ASFB numbers in the treated pond effluent often exceeded those of the influent. CONCLUSIONS: The results show that HRAPs are able to remove viral and bacterial indicators to levels acceptable for subsurface irrigation of nonfood crops. Additionally, it was concluded that alternate environmental sources and the potential for regrowth made ASFB unsuitable indicators for pathogenic protozoa in natural pond systems. SIGNIFICANCE AND IMPACT OF THE STUDY: This study shows HRAPs would be suitable replacements for WSPs in CWMS schemes in regard to pathogen disinfection. Such demonstration of the treatment efficacy of HRAPs, together with their smaller land area requirements relative to WSPs, should facilitate their wider adoption in rural and remote communities. PMID- 27187056 TI - Motor Cortex Reorganization and Repetitive Transcranial Magnetic Stimulation for Pain-A Methodological Study. AB - OBJECTIVES: Somatotopic reorganization of primary motor cortex (M1) has been described in several neurological conditions associated with chronic pain. We hypothesized that such reorganization impacts on the mechanisms of M1 stimulation induced analgesia and may either compromise the treatment effect of or provide an alternative target site for repetitive transcranial magnetic stimulation (rTMS). The aim of the study was to compare pain relief following rTMS of the standard motor "hotspot" with that of the reorganized area. MATERIAL AND METHODS: We used TMS motor mapping in 30 patients to establish the location of the standard motor "hotspot" (site A) and an alternative site located in the reorganized area (site B), both within M1. Where TMS mapping was not possible (N = 8) we determined the location of the two sites using task-related fMRI. We compared the analgesic effect on neuropathic pain of 5 sessions of navigated rTMS applied over (i) site A, (ii) site B, and (iii) occipital fissure (SHAM stimulation site). Total Pain Relief (TOTPAR) was determined as the difference in average weekly pain scores between baseline and following each rTMS cycle, over three weeks. RESULTS: Data from 27 patients was analyzed. rTMS of sites A and B resulted in greater TOTPAR than that of SHAM. No difference was seen between sites A and B. Responders (>=15% pain relief) were seen in both groups, with partial overlap only. Addition of stimulation over site B improved the responder rate by 58% compared with site A. In an open-label extension study of five sessions of rTMS aimed at the optimized target site, 8/11 responders and 1/12 nonresponders reported pain relief. CONCLUSIONS: Cortical reorganization may provide a more effective stimulation target for rTMS in some individuals with neuropathic pain. PMID- 27187058 TI - Trophic transfer of silver nanoparticles from earthworms disrupts the locomotion of springtails (Collembola). AB - Understanding how nanomaterials are transferred through food chains and evaluating their resulting toxicity is important. However, limited research has been conducted on the toxic consequences of trophically transferred nanomaterials in terrestrial ecosystems. In this study, we documented the adverse effects of trophically transferred silver nanoparticles (AgNPs) in a soil-earthworm (Eisenia andrei)-Collembola (Lobella sokamensis) food chain. We exposed E. andrei to soil with AgNPs at concentrations of 50, 200, and 500MUg AgNPs/g soil dry weight and assessed their survival after 7days. Trophic-transfer containers were then prepared and E. andrei that survived the 7days test period were washed, killed in boiling water, and added to the containers with L. sokamensis. We noted negligible effects and low bioaccumulation at the lowest AgNP concentration (50MUg AgNPs/g soil dry weight) in earthworms and the L. sokamensis that fed on them. The highest concentration of AgNPs (500MUg AgNPs/g soil dry weight) resulted in juvenile earthworm mortality and increased transfer of AgNPs to Collembola, which subsequently inhibited their locomotion. To our knowledge, this is the first study to document the trophic transfer and adverse effects of AgNPs in a soil-earthworm-Collembola food chain, a common prey-decomposer interaction in soil ecosystems. PMID- 27187057 TI - Does Context Matter? Examining PRISM as a Guiding Framework for Context-Specific Health Risk Information Seeking Among Young Adults. AB - Research indicates that when people seek health information, they typically look for information about a specific symptom, preventive measure, disease, or treatment. It is unclear, however, whether general or disease-specific theoretical models best predict how people search for health information. We surveyed undergraduates (N = 963) at a large public southeastern university to examine health information seeking in two incongruent health contexts (sexual health and cancer) to test whether a general model would hold for specific topics that differed in their immediate personal relevance for the target population. We found that the planned risk information seeking model was statistically a good fit for the data. Yet multiple predicted paths were not supported in either data set. Certain variables, such as attitudes, norms, and affect, appear to be strong predictors of intentions to seek information across health contexts. Implications for theory building, research methodology, and applied work in health-related risk information seeking are discussed. PMID- 27187059 TI - Variations and factors that influence the formation of polychlorinated naphthalenes in cement kilns co-processing solid waste. AB - Pilot studies of unintentionally produced pollutants should be performed before waste being co-processed in cement kilns. Polychlorinated naphthalene (PCN) formation and emission from cement kilns co-processing sorted municipal solid waste, sewage sludge, and waste acid, however, have not previously been studied. Here, PCNs were analyzed in stack gas samples and solid samples from different stages of three cement production runs. PCN destruction efficiencies were higher when waste was co-processed (93.1% and 88.7% in two tests) than when waste was not co-processed (39.1%), so co-processing waste would not increase PCN outputs. The PCN concentrations were higher in particle samples from the C1 preheater and stages at back end of kiln than in particle samples from other stages, suggesting that cyclone preheater and back end of kiln should be focused for controlling PCN emissions. Besides that, based on the variation of PCN concentrations and corresponding operating conditions in different stages, the temperature, feeding materials, and chlorine content were suggested as the main factors influencing PCN formation. The PCN homologue and congener profiles suggested chlorination and dechlorination were the main PCN formation and decomposition pathways, and congeners CN-23, CN-46, and CN-59 appear to be appropriate indicators of PCNs emitted from coal-burning sources. PMID- 27187060 TI - A link between poor quality antimalarials and malaria drug resistance? PMID- 27187062 TI - New RESOLVE-Based Diffusional Kurtosis Imaging in MRI-Visible Prostate Cancer: Effect of Reduced b Value on Image Quality and Diagnostic Effectiveness. AB - OBJECTIVE: The purpose of this article was to investigate whether a new readout segmentation of long variable echo-trains (RESOLVE)-based diffusional kurtosis imaging (DKI) with reduced b value technique can affect image quality and diagnostic effectiveness in MRI-visible prostate cancer (PCA). SUBJECTS AND METHODS: Prostatic RESOLVE DKI (0-1400 s/mm2) was prospectively performed for 12 volunteers. The optimal protocol was then performed in 108 MRI-visible PCAs to determine whether it can compete against a preferred b-value set (0-2000 s/mm(2)) regarding image quality and diagnostic effectiveness. Images were interpreted by two independent radiologists using the prostate imaging reporting and data system (PI-RADS). Readers' concordance and diagnostic effectiveness were tested with the Fleiss kappa and area under the ROC curve (Az) analyses. RESULTS: A b value of 1400 s/mm(2) generated a larger apparent diffusion coefficient of gaussian distribution (Dapp) (1.35 +/- 0.31 vs 1.30 +/- 0.30 mm(2)/s; p < 0.001) and apparent kurtosis coefficient (Kapp) (1.11 +/- 0.26 vs 1.00 +/- 0.21; p < 0.001) in PCA than did a b value of 2000 s/mm(2). Interreader agreement using PI-RADS was relatively low when Dapp and Kapp maps were excluded from image interpretations (kappa = 0.39-0.41 vs kappa = 0.66-0.68 with Dapp and Kapp maps). Interreader agreement in staging PCA was relatively high (kappa > 0.80) and was not influenced by reducing the b value. The power of Dapp and Kapp to differentiate PCA from normal tissue (Az = 0.97-0.98), tissue with a Gleason score less than or equal to 3 + 4 from tissue with a Gleason score greater than 3 + 4 (Az = 0.77-0.82), and PCA stage lower than pT3 from stage pT3 and higher PCA (Az = 0.70-0.75) was not significantly degraded by reducing the b value. CONCLUSION: We found that b values significantly influenced image quality, PI RADS score, and DKI outputs but did not degrade the diagnostic effectiveness of DKI parameters to detect and classify PCA. PMID- 27187063 TI - Multipole moments for embedding potentials: Exploring different atomic allocation algorithms. AB - Polarizable quantum mechanical (QM)/molecular mechanics (MM)-embedding methods are currently among the most promising methods for computationally feasible, yet reliable, production calculations of localized excitations and molecular response properties of large molecular complexes, such as proteins and RNA/DNA, and of molecules in solution. Our aim is to develop a computational methodology for distributed multipole moments and their associated multipole polarizabilities which is accurate, computationally efficient, and with smooth convergence with respect to multipole order. As the first step toward this goal, we herein investigate different ways of obtaining distributed atom-centered multipole moments that are used in the construction of the electrostatic part of the embedding potential. Our objective is methods that not only are accurate and computationally efficient, but which can be consistently extended with site polarizabilities including internal charge transfer terms. We present a new way of dealing with well-known problems in relation to the use of basis sets with diffuse functions in conventional atomic allocation algorithms, avoiding numerical integration schemes. Using this approach, we show that the classical embedding potential can be systematically improved, also when using basis sets with diffuse functions, and that very accurate embedding potentials suitable for QM/MM embedding calculations can be acquired. (c) 2016 Wiley Periodicals, Inc. PMID- 27187061 TI - Serum vitamin D levels correlate to coronary artery disease severity: a retrospective chart analysis. AB - BACKGROUND: The pro-atherosclerotic nature of vitamin D deficiency has been shown to increase cardiovascular events. We further emphasized and evaluated the severity of coronary artery disease (CAD) with varying levels of vitamin D in relation to age, gender, ethnicity and baseline confounders. METHODS: A retrospective, single-center study of 9,399 patients admitted between 2005 and 2014 for chest pain who underwent coronary angiography. Patients without a vitamin D level, measured as 25-dihydroxyvitamin D (25[OH]D) were excluded from our study. 25(OH)D deficiency and insufficiency were defined by having serum concentration levels of less than 20 ng/ml and 20 to 29.9 ng/ml, respectively, while normal levels were defined as greater than or equal to 30 ng/ml. We assessed levels of 25(OH)D and extent of coronary disease with coronary angiography as obstructive CAD (left main stenosis of >=50% or any stenosis of >=70%), non-obstructive CAD (>=1 stenosis >=20% but no stenosis >=70%) and normal coronaries (no stenosis >20%). RESULTS: Among 9,399 patients, 1,311 qualified, of which 308 patients (23%) had normal 25(OH)D levels, 552 patients (42%) had 25(OH)D deficiency and 451 patients (35%) had 25(OH)D insufficiency. In an analysis of the extent of coronary disease, we identified 20% of patients having normal coronaries, 55% having obstructive CAD and 25% having non-obstructive CAD. Baseline clinical risk factors and co-morbidities did not differ between the groups. Patients with normal 25(OH)D levels were found to have normal coronaries compared to patients with 25(OH)D deficiency or insufficiency (OR: 7, 95% CI: 5.2 - 9.5, p < 0.0001). Comparing patients with normal 25(OH)D levels, patients with 25(OH)D deficiency or insufficiency (<29 ng/ml), 62% were found to have obstructive CAD (n = 624, OR: 2.9, 95% CI: 2.3-3.7, p < 0.0001) and 25% had non obstructive CAD (n = 249, OR: 1.5, 95% CI: 1.1-2, p = 0.02). CONCLUSION: Normal coronaries and CAD were shown to correlate with normal and low levels of 25(OH)D, respectively. There is an inverse relationship between the percentage of coronary artery occlusion and serum 25(OH)D concentrations. Vitamin D may provide benefits in risk stratification of patients with CAD and serve as a possible risk factor. PMID- 27187065 TI - Prevalence of Bovine Mastitis Pathogens in Bulk Tank Milk in China. AB - The objectives of this study were to estimate the herd prevalence of major mastitis pathogens in bulk tank milk (BTM) in China dairy herds, to determine the relationship between the presence of mastitis pathogens and bulk tank milk somatic cell counts (BTSCC), and to investigate the impact of different dairy cattle farming modes and region on bacterial species. BTM samples collected from 894 dairy herds in China were examined for the presence of mastitis pathogens. The Flinders Technology Associates (FTA) cards were used for BTM sample collection, storage, and transportation and bacterial DNA amplification by real time PCR. Among contagious pathogens, Staphylococcus aureus, Streptococcus agalactiae, and Streptococcus dysgalactiae were detected in 50.1, 92.2, and 72.3% of the 894 BTM samples, respectively. Among environmental pathogens, E. coli, Streptococcus uberis, Enterococcus spp., Klebsiella spp., Serratia marcescens, Corynebacterium bovis, and Arcanobacterium pyogenes were detected in 28.6, 8.9, 35.7, 20.0, 1.3, 17.0, and 67.2% of the BTM samples, respectively. Staphylococcal beta-lactamase gene was detected in 61.7% of the BTM samples. The presence of Staphylococcus aureus and Arcanobacterium pyogenes were significantly associated with high BTSCC, respectively. Significant differences were found in presence of Staphylococcus aureus, Streptococcus agalactiae, and Streptococcus dysgalactiae in BTM sampled from the small household farms, dairy-farming communities, and large-scaled dairy farms. There were significant differences in the presence of Streptococcus agalactiae, Streptococcus dysgalactiae, Arcanobacterium pyogenes, staphylococcal beta-lactamase gene, Staphylococcus spp., Klebsiella spp., Enterococcus spp., and Streptococcus uberis in BTM among Inner Mongolia, Heilongjiang, and Hebei province. In conclusion, contagious mammary pathogens are predominated among pathogens in BTM samples in China. PMID- 27187064 TI - Corpus luteum as a novel target of weight changes that contribute to impaired female reproductive physiology and function. AB - Obesity and malnutrition are associated with decreased fecundity in women. Impaired reproductive capacity in obese women is often attributed to anovulation. However, obese women with ovulatory cycles also have reduced fertility, but the etiology of their impaired reproduction is only partially understood. Accumulating evidence suggests that obesity directly impairs oocyte and embryo quality as well as endometrial receptivity. In obese women, urinary progesterone metabolite excretion is decreased, but in excess of what can be explained by suppressed gonadotropin secretion, suggesting that apart from its central effect obesity may directly affect progesterone (P4) production. These observations have led to the novel hypothesis that obesity directly affects corpus luteum (CL) function. Similarly, we hypothesize that weight loss may contribute to luteal dysfunction. Here, we propose a non-human primate model, the vervet monkey, to examine the effect of weight gain and loss on menstrual cycle parameters and CL gene expression. In this model, weight gain and loss did not significantly alter menstrual cyclicity; however, both induced alterations in the CL transcriptome. In the weight gain monkey, we observed that impaired mid-luteal P4 secretion was associated with downregulation of steroidogenic pathways in CL. Collectively, these preliminary findings support our hypothesis that weight gain and loss may contribute to CL dysfunction. The vervet model described and preliminary observations provide a basis for a larger study to address this important question. Understanding the mechanisms by which weight gain and loss contribute to reproductive dysfunction can assist in the development of targeted treatments to enhance women's reproductive capability when it is desired. ABBREVIATIONS: CL: corpus luteum; P4: progesterone; E2: estradiol; PDG: pregnanediol 3-glucoronide; LH: luteinizing hormone; FSH: follicle-stimulating hormone; GnRH: gonadotropin releasing hormone; BMI: body mass index; qrtPCR: quantitative real-time PCR; PGR: progesterone receptor; ART: assisted reproductive technology; IVF: in vitro fertilization; HPO: hypothalamic-pituitary-ovarian axis; MMPs: matrix metalloproteinases Gene symbols: LH receptor (LHGCR); cholesterol side-chain cleavage enzyme (CYP11A1); 3 beta-hydroxysteroid dehydrogenase type II (HSD3B2); steroidogenic acute regulatory protein (STAR); LDL receptor (LDLR); scavenger receptor B1 (SCARB1); ATP-binding cassette sub-family A member 1 (ABCA1); ATP binding cassette sub-family G member 1 (ABCG1); apolipoprotein A (APOA1); 24 dehydrocholesterol reductase (DHCR24); 3-hydroxy-3-methylglytaryl-CoA reductase (HMGCR); vascular endothelial growth factor A (VEGFA); vascular endothelial growth factor C (VEGFC); vascular endothelial growth factor receptor 1 (VEGFR1); and TIMP metallopeptidase inhibitor 1 (TIMP1); amphiregulin (AREG); epiregulin (EREG); CCAAT/enhancer binding protein alpha (CEBPBA); cAMP responsive element binding protein 3-like 1 (CREB3L1); ADAM metallopeptidase with thrombospodin type 1 motif 1 (ADAMTS1); matrix metallopeptidase 9 (MMP9); cytochrome b-245 beta polypeptide (CYBB or NOX2); NADH oxidase (NCF2 or NOXA2); Fc fragment of IgG receptor IIb (FCGR2B); Fc fragment of IgG receptor IIb (FCGR2C); ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1); RAB27A member RAS oncofamily (RAB27A); hydroxyprostaglandin dehydrogenase (HPGD); prostaglandin-endoperoxidase synthase 1 (PTGS1); integrin B2 (ITGB2); leukotriene A4 hydrolase (LTA4H); radixin (RDX); ezrin (EZR); nuclear receptor subfamily 5 group A member 2 (NR5A2). PMID- 27187066 TI - Activation of RhoA, but Not Rac1, Mediates Early Stages of S1P-Induced Endothelial Barrier Enhancement. AB - Compromised endothelial barrier function is a hallmark of inflammation. Rho family GTPases are critical in regulating endothelial barrier function, yet their precise roles, particularly in sphingosine-1-phosphate (S1P)-induced endothelial barrier enhancement, remain elusive. Confluent cultures of human umbilical vein endothelial cells (HUVEC) or human dermal microvascular endothelial cells (HDMEC) were used to model the endothelial barrier. Barrier function was assessed by determining the transendothelial electrical resistance (TER) using an electrical cell-substrate impedance sensor (ECIS). The roles of Rac1 and RhoA were tested in S1P-induced barrier enhancement. The results show that pharmacologic inhibition of Rac1 with Z62954982 failed to block S1P-induced barrier enhancement. Likewise, expression of a dominant negative form of Rac1, or knockdown of native Rac1 with siRNA, failed to block S1P-induced elevations in TER. In contrast, blockade of RhoA with the combination of the inhibitors Rhosin and Y16 significantly reduced S1P-induced increases in TER. Assessment of RhoA activation in real time using a fluorescence resonance energy transfer (FRET) biosensor showed that S1P increased RhoA activation primarily at the edges of cells, near junctions. This was complemented by myosin light chain-2 phosphorylation at cell edges, and increased F-actin and vinculin near intercellular junctions, which could all be blocked with pharmacologic inhibition of RhoA. The results suggest that S1P causes activation of RhoA at the cell periphery, stimulating local activation of the actin cytoskeleton and focal adhesions, and resulting in endothelial barrier enhancement. S1P-induced Rac1 activation, however, does not appear to have a significant role in this process. PMID- 27187067 TI - Engineering electrocatalytic activity in nanosized perovskite cobaltite through surface spin-state transition. AB - The activity of electrocatalysts exhibits a strongly dependence on their electronic structures. Specifically, for perovskite oxides, Shao-Horn and co workers have reported a correlation between the oxygen evolution reaction activity and the eg orbital occupation of transition-metal ions, which provides guidelines for the design of highly active catalysts. Here we demonstrate a facile method to engineer the eg filling of perovskite cobaltite LaCoO3 for improving the oxygen evolution reaction activity. By reducing the particle size to ~80 nm, the eg filling of cobalt ions is successfully increased from unity to near the optimal configuration of 1.2 expected by Shao-Horn's principle. Consequently, the activity is significantly enhanced, comparable to those of recently reported cobalt oxides with eg(~1.2) configurations. This enhancement is ascribed to the emergence of spin-state transition from low-spin to high-spin states for cobalt ions at the surface of the nanoparticles, leading to more active sites with increased reactivity. PMID- 27187068 TI - Simulating Flying Insects Using Dynamics and Data-Driven Noise Modeling to Generate Diverse Collective Behaviors. AB - We present a biologically plausible dynamics model to simulate swarms of flying insects. Our formulation, which is based on biological conclusions and experimental observations, is designed to simulate large insect swarms of varying densities. We use a force-based model that captures different interactions between the insects and the environment and computes collision-free trajectories for each individual insect. Furthermore, we model the noise as a constructive force at the collective level and present a technique to generate noise-induced insect movements in a large swarm that are similar to those observed in real world trajectories. We use a data-driven formulation that is based on pre recorded insect trajectories. We also present a novel evaluation metric and a statistical validation approach that takes into account various characteristics of insect motions. In practice, the combination of Curl noise function with our dynamics model is used to generate realistic swarm simulations and emergent behaviors. We highlight its performance for simulating large flying swarms of midges, fruit fly, locusts and moths and demonstrate many collective behaviors, including aggregation, migration, phase transition, and escape responses. PMID- 27187069 TI - Neuronal Allocation to a Hippocampal Engram. AB - The dentate gyrus (DG) is important for encoding contextual memories, but little is known about how a population of DG neurons comes to encode and support a particular memory. One possibility is that recruitment into an engram depends on a neuron's excitability. Here, we manipulated excitability by overexpressing CREB in a random population of DG neurons and examined whether this biased their recruitment to an engram supporting a contextual fear memory. To directly assess whether neurons overexpressing CREB at the time of training became critical components of the engram, we examined memory expression while the activity of these neurons was silenced. Chemogenetically (hM4Di, an inhibitory DREADD receptor) or optogenetically (iC++, a light-activated chloride channel) silencing the small number of CREB-overexpressing DG neurons attenuated memory expression, whereas silencing a similar number of random neurons not overexpressing CREB at the time of training did not. As post-encoding reactivation of the activity patterns present during initial experience is thought to be important in memory consolidation, we investigated whether post-training silencing of neurons allocated to an engram disrupted subsequent memory expression. We found that silencing neurons 5 min (but not 24 h) following training disrupted memory expression. Together these results indicate that the rules of neuronal allocation to an engram originally described in the lateral amygdala are followed in different brain regions including DG, and moreover, that disrupting the post training activity pattern of these neurons prevents memory consolidation. PMID- 27187072 TI - Direct Observation of Pressure-Driven Valence Electron Transfer in Ba3BiRu2O9, Ba3BiIr2O9, and Ba4BiIr3O12. AB - The hexagonal perovskites Ba3BiIr2O9, Ba3BiRu2O9, and Ba4BiIr3O12 all undergo pressure-induced 1% volume collapses above 5 GPa. These first-order transitions have been ascribed to internal transfer of valence electrons between bismuth and iridium/ruthenium, which is driven by external applied pressure because the reduction in volume achieved by emptying the 6s shell of bismuth upon oxidation to Bi(5+) is greater in magnitude than the increase in volume by reducing iridium or ruthenium. Here, we report direct observation of these valence transfers for the first time, using high-pressure X-ray absorption near-edge spectroscopy (XANES) measurements. Our data also support the highly unusual "4+" nominal oxidation state of bismuth in these compounds, although the possibility of local disproportionation into Bi(3+)/Bi(5+) cannot be definitively ruled out. Ab initio calculations reproduce the transition, support its interpretation as a valence electron transfer from Bi to Ir/Ru, and suggest that the high-pressure phase may show metallic behavior (in contrast to the insulating ambient-pressure phase). PMID- 27187070 TI - Phenome-Wide Association Study for Alcohol and Nicotine Risk Alleles in 26394 Women. AB - To identify novel traits associated with alleles known to predispose to alcohol and nicotine use, we conducted a phenome-wide association study (PheWAS) in a large multi-population cohort. We investigated 7688 African-Americans, 1133 Asian Americans, 14 081 European-Americans, and 3492 Hispanic-Americans from the Women's Health Initiative, analyzing alleles at the CHRNA3-CHRNA5 locus, ADH1B, and ALDH2 with respect to phenotypic traits related to anthropometric characteristics, dietary habits, social status, psychological traits, reproductive history, health conditions, and nicotine/alcohol use. In ADH1B trans population meta-analysis and population-specific analysis, we replicated prior associations with drinking behaviors and identified multiple novel phenome-wide significant and suggestive findings related to psychological traits, socioeconomic status, vascular/metabolic conditions, and reproductive health. We then applied Bayesian network learning algorithms to provide insight into the causative relationships of the novel ADH1B associations: ADH1B appears to affect phenotypic traits via both alcohol-mediated and alcohol-independent effects. In an independent sample of 2379 subjects, we also replicated the novel ADH1B associations related to socioeconomic status (household gross income and highest grade finished in school). For CHRNA3-CHRNA5 risk alleles, we replicated association with smoking behaviors, lung cancer, and asthma. There were also novel suggestive CHRNA3-CHRNA5 findings with respect to high-cholesterol medication use and distrustful attitude. In conclusion, the genetics of alcohol and tobacco use potentially has broader implications on physical and mental health than is currently recognized. In particular, ADH1B may be a gene relevant for the human phenome via both alcohol metabolism-related mechanisms and other alcohol metabolism-independent mechanisms. PMID- 27187071 TI - Bacterial Diversity and Community Structure in Korean Ginseng Field Soil Are Shifted by Cultivation Time. AB - Traditional molecular methods have been used to examine bacterial communities in ginseng-cultivated soil samples in a time-dependent manner. Despite these efforts, our understanding of the bacterial community is still inadequate. Therefore, in this study, a high-throughput sequencing approach was employed to investigate bacterial diversity in various ginseng field soil samples over cultivation times of 2, 4, and 6 years in the first and second rounds of cultivation. We used non-cultivated soil samples to perform a comparative study. Moreover, this study assessed changes in the bacterial community associated with soil depth and the health state of the ginseng. Bacterial richness decreased through years of cultivation. This study detected differences in relative abundance of bacterial populations between the first and second rounds of cultivation, years of cultivation, and health states of ginseng. These bacterial populations were mainly distributed in the classes Acidobacteria, Alphaproteobacteria, Deltaproteobacteria, Gammaproteobacteria, and Sphingobacteria. In addition, we found that pH, available phosphorus, and exchangeable Ca+ seemed to have high correlations with bacterial class in ginseng cultivated soil. PMID- 27187074 TI - Artificial Intelligence Procedures for Tree Taper Estimation within a Complex Vegetation Mosaic in Brazil. AB - Tree stem form in native tropical forests is very irregular, posing a challenge to establishing taper equations that can accurately predict the diameter at any height along the stem and subsequently merchantable volume. Artificial intelligence approaches can be useful techniques in minimizing estimation errors within complex variations of vegetation. We evaluated the performance of Random Forest(r) regression tree and Artificial Neural Network procedures in modelling stem taper. Diameters and volume outside bark were compared to a traditional taper-based equation across a tropical Brazilian savanna, a seasonal semi deciduous forest and a rainforest. Neural network models were found to be more accurate than the traditional taper equation. Random forest showed trends in the residuals from the diameter prediction and provided the least precise and accurate estimations for all forest types. This study provides insights into the superiority of a neural network, which provided advantages regarding the handling of local effects. PMID- 27187075 TI - When Wavelengths Collide: Bias in Cell Abundance Measurements Due to Expressed Fluorescent Proteins. AB - The abundance of bacteria in liquid culture is commonly inferred by measuring optical density at 600 nm. Red fluorescent proteins (RFPs) can strongly absorb light at 600 nm. Increasing RFP expression can falsely inflate apparent cell density and lead to underestimations of mean per-cell fluorescence by up to 10%. Measuring optical density at 700 nm would allow estimation of cell abundance unaffected by the presence of nearly all fluorescent proteins. PMID- 27187073 TI - Use of Extended Characteristics of Locomotion and Feeding Behavior for Automated Identification of Lame Dairy Cows. AB - This study was carried out to detect differences in locomotion and feeding behavior in lame (group L; n = 41; gait score >= 2.5) and non-lame (group C; n = 12; gait score <= 2) multiparous Holstein cows in a cross-sectional study design. A model for automatic lameness detection was created, using data from accelerometers attached to the hind limbs and noseband sensors attached to the head. Each cow's gait was videotaped and scored on a 5-point scale before and after a period of 3 consecutive days of behavioral data recording. The mean value of 3 independent experienced observers was taken as a definite gait score and considered to be the gold standard. For statistical analysis, data from the noseband sensor and one of two accelerometers per cow (randomly selected) of 2 out of 3 randomly selected days was used. For comparison between group L and group C, the T-test, the Aspin-Welch Test and the Wilcoxon Test were used. The sensitivity and specificity for lameness detection was determined with logistic regression and ROC-analysis. Group L compared to group C had significantly lower eating and ruminating time, fewer eating chews, ruminating chews and ruminating boluses, longer lying time and lying bout duration, lower standing time, fewer standing and walking bouts, fewer, slower and shorter strides and a lower walking speed. The model considering the number of standing bouts and walking speed was the best predictor of cows being lame with a sensitivity of 90.2% and specificity of 91.7%. Sensitivity and specificity of the lameness detection model were considered to be very high, even without the use of halter data. It was concluded that under the conditions of the study farm, accelerometer data were suitable for accurately distinguishing between lame and non-lame dairy cows, even in cases of slight lameness with a gait score of 2.5. PMID- 27187076 TI - Correction: First Evidence of Intraclonal Genetic Exchange in Trypanosomatids Using Two Leishmania infantum Fluorescent Transgenic Clones. AB - [This corrects the article DOI: 10.1371/journal.pntd.0003075.]. PMID- 27187078 TI - Topochemistry of Bowtie- and Star-Shaped Metal Dichalcogenide Nanoisland Formation. AB - A large number of experimental studies over the past few years observed the formation of unusual highly symmetric polycrystalline twinned nanoislands of transition metal dichalcogenides, resembling bowties or stars. Here, we analyze their morphology in terms of equilibrium and growth shapes. We propose a mechanism for these complex shapes' formation via collision of concurrently growing islands and validate the theory with phase-field simulations that demonstrate how highly symmetric structures can actually emerge from arbitrary starting conditions. Finally, we use first-principles calculations to propose an explanation of the predominance of high-symmetry polycrystals with 60 degrees lattice misorientation angles. PMID- 27187077 TI - Hippocampal volume in patients with asthma: Results from the Dallas Heart Study. AB - INTRODUCTION: Asthma is associated with an increased risk of mild cognitive impairment and dementia. Depression and oral corticosteroid use are associated with atrophy of the hippocampus and are common in asthma. However, minimal neuroimaging data are available in asthma patients. METHODS: We conducted a retrospective analysis of 1,287 adult participants from the Dallas Heart Study, an epidemiological sample of Dallas County residents. Study outcome variables were hippocampal volumes measured by FreeSurfer. ANOVA was used to examine a gender difference in hippocampal volumes. General Linear Models (GLM) were conducted to examine asthma diagnosis association with hippocampal volumes. RESULTS: The prevalence rate of asthma among our study sample was 10.8% with 9.6% in males and 11.7% in females. After controlling for demographic characteristics, participants with asthma had significantly smaller total, right, and left hippocampal volumes than those without asthma. The association of asthma with smaller hippocampal volume was significant among males but not among females. CONCLUSION: Hippocampal volume in a large and diverse sample of adults was significantly smaller in people with asthma as compared to those without asthma. These findings suggest that asthma may be associated with structural brain differences. Thus, medical illnesses without obvious direct neurodegenerative or even vascular involvement can be associated with brain changes. Because the hippocampus is a brain region involved in memory formation, these findings may have implications for treatment adherence that could have important implications for asthma treatment. Study limitations are the reliance on a self-reported asthma diagnosis and lack of additional asthma clinical information. PMID- 27187081 TI - PCSK1 Mutations and Human Endocrinopathies: From Obesity to Gastrointestinal Disorders. AB - Prohormone convertase 1/3, encoded by the PCSK1 gene, is a serine endoprotease that is involved in the processing of a variety of proneuropeptides and prohormones. Humans who are homozygous or compound heterozygous for loss-of function mutations in PCSK1 exhibit a variable and pleiotropic syndrome consisting of some or all of the following: obesity, malabsorptive diarrhea, hypogonadotropic hypogonadism, altered thyroid and adrenal function, and impaired regulation of plasma glucose levels in association with elevated circulating proinsulin-to-insulin ratio. Recently, more common variants in the PCSK1 gene have been found to be associated with alterations in body mass index, increased circulating proinsulin levels, and defects in glucose homeostasis. This review provides an overview of the endocrinopathies and other disorders observed in prohormone convertase 1/3-deficient patients, discusses the possible biochemical basis for these manifestations of the disease, and proposes a model whereby certain missense mutations in PCSK1 may result in proteins with a dominant negative action. PMID- 27187079 TI - An Oncogenic Virus Promotes Cell Survival and Cellular Transformation by Suppressing Glycolysis. AB - Aerobic glycolysis is essential for supporting the fast growth of a variety of cancers. However, its role in the survival of cancer cells under stress conditions is unclear. We have previously reported an efficient model of gammaherpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV)-induced cellular transformation of rat primary mesenchymal stem cells. KSHV-transformed cells efficiently induce tumors in nude mice with pathological features reminiscent of Kaposi's sarcoma tumors. Here, we report that KSHV promotes cell survival and cellular transformation by suppressing aerobic glycolysis and oxidative phosphorylation under nutrient stress. Specifically, KSHV microRNAs and vFLIP suppress glycolysis by activating the NF-kappaB pathway to downregulate glucose transporters GLUT1 and GLUT3. While overexpression of the transporters rescues the glycolytic activity, it induces apoptosis and reduces colony formation efficiency in softagar under glucose deprivation. Mechanistically, GLUT1 and GLUT3 inhibit constitutive activation of the AKT and NF-kappaB pro-survival pathways. Strikingly, GLUT1 and GLUT3 are significantly downregulated in KSHV infected cells in human KS tumors. Furthermore, we have detected reduced levels of aerobic glycolysis in several KSHV-infected primary effusion lymphoma cell lines compared to a Burkitt's lymphoma cell line BJAB, and KSHV infection of BJAB cells reduced aerobic glycolysis. These results reveal a novel mechanism by which an oncogenic virus regulates a key metabolic pathway to adapt to stress in tumor microenvironment, and illustrate the importance of fine-tuning the metabolic pathways for sustaining the proliferation and survival of cancer cells, particularly under stress conditions. PMID- 27187082 TI - DNA Transposition at Work. AB - DNA transposons are defined segments of DNA that are able to move from one genomic location to another. Movement is facilitated by one or more proteins, called the transposase, typically encoded by the mobile element itself. Here, we first provide an overview of the classification of such mobile elements in a variety of organisms. From a mechanistic perspective, we have focused on one particular group of DNA transposons that encode a transposase with a DD(E/D) catalytic domain that is topologically similar to RNase H. For these, a number of three-dimensional structures of transpososomes (transposase-nucleic acid complexes) are available, and we use these to describe the basics of their mechanisms. The DD(E/D) group, in addition to being the largest and most common among all DNA transposases, is the one whose members have been used for a wide variety of genomic applications. Therefore, a second focus of the article is to provide a nonexhaustive overview of transposon applications. Although several non transposon-based approaches to site-directed genome modifications have emerged in the past decade, transposon-based applications are highly relevant when integration specificity is not sought. In fact, for many applications, the almost perfect randomness and high frequency of integration make transposon-based approaches indispensable. PMID- 27187083 TI - Targeting and Treatment of Tumor Hypoxia by Newly Designed Prodrug Possessing High Permeability in Solid Tumors. AB - Tumor hypoxia, which is associated with poor prognosis in cancer, is known to lead to resistance to radiotherapy and anticancer chemotherapy. Impaired drug penetration in hypoxic regions has been recognized as an essential barrier to drug development in solid tumors. Here, we propose novel hypoxia-activated prodrugs, which drastically improved the penetration property of commonly used anticancer drugs in the hypoxic region. In this design, conventional anticancer drugs were modified with 2-nitroimidazole derivatives. The most important point of this study was that the prodrug designed formed a 6-membered cyclic structure to allow liberation of the active drug in the hypoxic region. This design markedly increased the selectivity of the hypoxia-targeted prodrug, resulting in significant reduction of adverse effects in the normoxic region. In vitro studies confirmed the selective activation under hypoxic conditions. In vivo studies showed drastic reduction of adverse effects associated with conventional anticancer drugs and improvement of the survival rate of mice. Immunofluorescence analyses confirmed that the designed prodrug had a tendency to localize at the hypoxic region, in contrast to conventional anticancer drugs, which localize only at the normoxic region. PMID- 27187080 TI - Maternal Hyperleptinemia Is Associated with Male Offspring's Altered Vascular Function and Structure in Mice. AB - Children of mothers with gestational diabetes have greater risk of developing hypertension but little is known about the mechanisms by which this occurs. The objective of this study was to test the hypothesis that high maternal concentrations of leptin during pregnancy, which are present in mothers with gestational diabetes and/or obesity, alter blood pressure, vascular structure and vascular function in offspring. Wildtype (WT) offspring of hyperleptinemic, normoglycemic, Leprdb/+ dams were compared to genotype matched offspring of WT control dams. Vascular function was assessed in male offspring at 6, and at 31 weeks of age after half the offspring had been fed a high fat, high sucrose diet (HFD) for 6 weeks. Blood pressure was increased by HFD but not affected by maternal hyperleptinemia. On a standard diet, offspring of hyperleptinemic dams had outwardly remodeled mesenteric arteries and an enhanced vasodilatory response to insulin. In offspring of WT but not Leprdb/+ dams, HFD induced vessel hypertrophy and enhanced vasodilatory responses to acetylcholine, while HFD reduced insulin responsiveness in offspring of hyperleptinemic dams. Offspring of hyperleptinemic dams had stiffer arteries regardless of diet. Therefore, while maternal hyperleptinemia was largely beneficial to offspring vascular health under a standard diet, it had detrimental effects in offspring fed HFD. These results suggest that circulating maternal leptin concentrations may interact with other factors in the pre- and post -natal environments to contribute to altered vascular function in offspring of diabetic pregnancies. PMID- 27187085 TI - Correction to Synthesis of Omphadiol and Pyxidatol C. PMID- 27187084 TI - Enhancing the Enrichment of Pharmacophore-Based Target Prediction for the Polypharmacological Profiles of Drugs. AB - PharmMapper is a web server for drug target identification by reversed pharmacophore matching the query compound against an annotated pharmacophore model database, which provides a computational polypharmacology prediction approach for drug repurposing and side effect risk evaluation. But due to the inherent nondiscriminative feature of the simple fit scores used for prediction results ranking, the signal/noise ratio of the prediction results is high, posing a challenge for predictive reliability. In this paper, we improved the predictive accuracy of PharmMapper by generating a ligand-target pairwise fit score matrix from profiling all the annotated pharmacophore models against corresponding ligands in the original complex structures that were used to extract these pharmacophore models. The matrix reflects the noise baseline of fit score distribution of the background database, thus enabling estimation of the probability of finding a given target randomly with the calculated ligand pharmacophore fit score. Two retrospective tests were performed which confirmed that the probability-based ranking score outperformed the simple fit score in terms of identification of both known drug targets and adverse drug reaction related off-targets. PMID- 27187086 TI - Disparities in cancer treatment among patients infected with the human immunodeficiency virus. AB - BACKGROUND: Patients with cancer who are infected with the human immunodeficiency virus (HIV) are less likely to receive cancer treatment compared with HIV uninfected individuals. However, to the authors' knowledge, the impact of insurance status and comorbidities is unknown. METHODS: Data from the National Cancer Data Base were used to study nonelderly adults diagnosed with several common cancers from 2003 to 2011. Cancer treatment was defined as chemotherapy, surgery, radiotherapy, or any combination during the first course of treatment. Multivariate logistic regression was used to examine associations between HIV status and lack of cancer treatment, and identify predictors for lack of treatment among HIV-infected patients. RESULTS: A total of 10,265 HIV-infected and 2,219,232 HIV-uninfected cases were included. In multivariate analysis, HIV infected patients with cancer were found to be more likely to lack cancer treatment for cancers of the head and neck (adjusted odds ratio [aOR], 1.48; 95% confidence interval [95% CI], 1.09-2.01), upper gastrointestinal tract (aOR, 2.62; 95% CI, 2.04-3.37), colorectum (aOR, 1.70; 95% CI, 1.17-2.48), lung (aOR, 2.46; 95% CI, 2.19-2.76), breast (aOR, 2.14; 95% CI, 1.16-3.98), cervix (aOR, 2.81; 95% CI, 1.77-4.45), prostate (aOR, 2.16; 95% CI, 1.69-2.76), Hodgkin lymphoma (aOR, 1.92; 95% CI, 1.66-2.22), and diffuse large B-cell lymphoma (aOR, 1.82; 95% CI, 1.65-2.00). Predictors of a lack of cancer treatment among HIV infected individuals varied by tumor type (solid tumor vs lymphoma), but black race and a lack of private insurance were found to be predictors for both groups. CONCLUSIONS: In the United States, HIV-infected patients with cancer appear to be less likely to receive cancer treatment regardless of insurance and comorbidities. To the authors' knowledge, the current study is the largest study of cancer treatment in HIV-infected patients with cancer in the United States and provides evidence of cancer treatment disparities even after controlling for differences with regard to insurance status and comorbidities. Further work should focus on addressing differential cancer treatment. Cancer 2016;122:2399 2407. (c) 2016 American Cancer Society. PMID- 27187087 TI - Construct and diagnostic validities of the Free and Cued Selective Reminding Test in the Alzheimer's disease spectrum. AB - INTRODUCTION: The Free and Cued Selective Reminding Test (FCSRT) is a memory test that controls attention and acquisition, by providing category cues in the learning process. Because it enables an assessment of memory not confounded by normal age-related changes in cognition and a high accuracy on Alzheimer's disease (AD) evaluation, it has been suggested by the International Working Group on AD. Our aim was to assess the construct related validity of the FCSRT in the AD spectrum disorders. METHOD: Patients were classified in two groups according to standard criteria: amnestic mild cognitive impairment (n = 100) and AD (n = 70). A matched control group (n = 101) of cognitively healthy subjects was included. The factorial structure of two models and respective construct and diagnostic validities were analyzed. RESULTS: Both models revealed adequate fit values. The appropriated convergent validity and the lack of discriminant validity support the two factors as measuring the same construct (memory ability). The recalls of the FCSRT enabled high classification accuracy and diagnostic validity for both pathological groups. CONCLUSIONS: This study represents a novel contribution regarding the adequacy of the FCSRT in terms of construct and diagnostic validities and shows the interest of including both immediate (learning) and delayed (retention) recalls. It gives also new possibilities regarding the use of the FCSRT in the memory assessment of AD spectrum disorders. PMID- 27187092 TI - A Randomized Trial on the Effect of Exercise Mode on Breast Cancer-Related Lymphedema. AB - PURPOSE: Breast cancer-related lymphedema is a common and debilitating side effect of cancer treatment. This randomized trial compared the effect of progressive resistance- or aerobic-based exercise on breast cancer-related lymphedema extent and severity, as well as participants' muscular strength and endurance, aerobic fitness, body composition, upper-body function, and quality of life. METHODS: Women with a clinical diagnosis of stable unilateral, upper-limb lymphedema secondary to breast cancer were randomly allocated to a resistance based (n = 21) or aerobic-based (n = 20) exercise group (12-wk intervention). Women were assessed preintervention, postintervention, and 12 wk postintervention, with generalized estimating equation models used to compare over time changes in each group's lymphedema (two-tailed P < 0.05). RESULTS: Lymphedema remained stable in both groups (as measured by bioimpedance spectroscopy and circumferences), with no significant differences between groups noted in lymphedema status. There was a significant (P < 0.01) time-group effect for upper-body strength (assessed using four to six repetition maximum bench press), with the resistance-based exercise group increasing strength by 4.2 kg (95% confidence interval [CI] = 3.2-5.2) postintervention compared with 1.2 kg (95% CI = -0.1 to 2.5) in the aerobic-based exercise group. Although not supported statistically, the aerobic-based exercise group reported a clinically relevant decline in number of symptoms postintervention (-1.5, 95% CI = -2.6 to 0.3), and women in both exercise groups experienced clinically meaningful improvements in lower-body endurance, aerobic fitness, and quality of life by 12 wk follow-up. DISCUSSION: Participating in resistance- or aerobic-based exercise did not change lymphedema status but led to clinically relevant improvements in function and quality of life, with findings suggesting that neither mode is superior with respect to lymphedema effect. As such, personal preferences, survivorship concerns, and functional needs are important and relevant considerations when prescribing exercise mode to those with secondary lymphedema. PMID- 27187094 TI - Strategic Priorities for Physical Activity Surveillance in the United States. AB - PURPOSE: Develop strategic priorities to guide future physical activity surveillance in the United States. METHODS: The Centers for Disease Control and Prevention and the American College of Sports Medicine convened a scientific roundtable of physical activity and measurement experts. Participants summarized the current state of aerobic physical activity surveillance for adults, focusing on practice and research needs in three areas: 1) behavior, 2) human movement, and 3) community supports. Needs and challenges for each area were identified. At the conclusion of the meeting, experts identified one overarching strategy and five strategic priorities to guide future surveillance. RESULTS: The identified overarching strategy was to develop a national plan for physical activity surveillance similar to the U.S. National Physical Activity Plan for promotion. The purpose of the plan would be to enhance coordination and collaboration within and between sectors, such as transportation and public health, and to address specific strategic priorities identified at the roundtable. These strategic priorities were used 1) to identify and prioritize physical activity constructs; 2) to assess the psychometric properties of instruments for physical activity surveillance; 3) to provide training and technical assistance for those collecting, analyzing, or interpreting surveillance data; 4) to explore accessing data from alternative sources; and 5) to improve communication, translation, and dissemination about estimates of physical activity from surveillance systems. CONCLUSION: This roundtable provided strategic priorities for physical activity surveillance in the United States. A first step is to develop a national plan for physical activity surveillance that would provide an operating framework from which to execute these priorities. PMID- 27187093 TI - Effect of Acute Exercise on Fatigue in People with ME/CFS/SEID: A Meta-analysis. AB - PURPOSE: A prominent symptom of myalgic encephalomyelitis, chronic fatigue syndrome, or systemic exertion intolerance disease (ME/CFS/SEID) is persistent fatigue that is worsened by physical exertion. Here the population effect of a single bout of exercise on fatigue symptoms in people with ME/CFS/SEID was estimated and effect moderators were identified. METHODS: Google Scholar was systematically searched for peer-reviewed articles published between February 1991 and May 2015. Studies were included where people diagnosed with ME/CFS/SEID and matched control participants completed a single bout of exercise and fatigue self-reports were obtained before and after exercise. Fatigue means, standard deviations, and sample sizes were extracted to calculate effect sizes and the 95% confidence interval. Effects were pooled using a random-effects model and corrected for small sample bias to generate mean Delta. Multilevel regression modeling adjusted for nesting of effects within studies. Moderators identified a priori were diagnostic criteria, fibromyalgia comorbidity, exercise factors (intensity, duration, and type), and measurement factors. RESULTS: Seven studies examining 159 people with ME/CFS/SEID met inclusion criteria, and 47 fatigue effects were derived. The mean fatigue effect was Delta = 0.73 (95% confidence interval = 0.24-1.23). Fatigue increases were larger for people with ME/CFS/SEID when fatigue was measured 4 h or more after exercise ended rather than during or immediately after exercise ceased. CONCLUSIONS: This preliminary evidence indicates that acute exercise increases fatigue in people with ME/CFS/SEID more than that in control groups, but effects were heterogeneous between studies. Future studies with no-exercise control groups of people with ME/CFS/SEID are needed to obtain a more precise estimate of the effect of exercise on fatigue in this population. PMID- 27187096 TI - Contralateral Repeated Bout Effect of Eccentric Exercise of the Elbow Flexors. AB - PURPOSE: This study compared the magnitude of the repeated bout effect (RBE) for different time intervals between two bouts of eccentric exercise of the elbow flexors to better understand the contralateral RBE (CL-RBE). METHODS: Untrained young men (22.0 +/- 1.8 yr) were allocated to either a control or one of seven CL RBE groups (n = 13 per group). The CL-RBE groups performed exercise consisting of 30 maximal isokinetic (30 degrees .s) eccentric contractions of the elbow flexors (ECC1) with either dominant or nondominant arm followed 0.5 h, 6 h, 12 h, 24 h (1 d), 7 d (1 wk), 28 d (4 wk), or 56 d (8 wk) by the same exercise (ECC2) using the opposite arm. The control group used the nondominant arm for ECC1 and ECC2 separated by 2 wk. RESULTS: Maximal voluntary concentric contraction torque, peak torque angle, range of motion, upper arm circumference, muscle soreness, ultrasound echo intensity, and plasma creatine kinase activity and myoglobin concentration changed (P < 0.05) after ECC1, without significant difference among the groups. Changes in all variables after ECC2 were smaller (P < 0.05) than those after ECC1 for the control, 1 d, 1 wk, and 4 wk groups, indicating the RBE. However, the changes were not significantly different between ECC1 and ECC2 for the 0.5 h, 6 h, 12 h, and 8 wk groups. The difference in the changes in all variables between ECC1 and ECC2 was smaller for the 1 d (70%), 1 wk (55%), and 4 wk (36%) than the control group (91%), and the magnitude of the CL-RBE was reduced with increasing the time between bouts from 1 d to 4 wk (P < 0.05). CONCLUSION: These results suggest that the CL-RBE lasts shorter than the ipsilateral RBE (>8 wk) and requires a day to be conferred. PMID- 27187097 TI - High-Intensity Interval Training for Cognitive and Mental Health in Adolescents. AB - PURPOSE: Emerging literature suggests that physical activity and fitness may have a positive effect on cognitive and mental health in adolescents. The purpose of the current study was to evaluate the efficacy of two high-intensity interval training (HIIT) protocols for improving cognitive and mental health outcomes (executive function, psychological well-being, psychological distress, and physical self-concept) in adolescents. METHODS: Participants (n = 65; mean age = 15.8 +/- 0.6 yr) were randomized to three conditions: aerobic exercise program (AEP; n = 21), resistance and aerobic program (RAP; n = 22), and control (n = 22). HIIT sessions (8-10 min per session) were delivered during physical education lessons or at lunchtime three times per week for 8 wk. Assessments were conducted at baseline and immediately postintervention to detect changes in executive function (trail making test), psychological well-being, psychological distress, and physical self-description by researchers blinded to treatment allocation. Intervention effects were examined using linear mixed models. Cohen's d effect sizes and clinical inference were also calculated. RESULTS: While results were not significant, small improvements in executive function (mean change (95% CI) -6.69 (-22.03, 8.64), d = -0.32) and psychological well-being (mean change (95% CI) 2.81 (-2.06, 7.68), d = 0.34) were evident in the AEP group; and moderate improvements in executive function (mean change (95% CI) 10.73 (-26.22, 4.76), d = -0.51), and small improvements in well-being (mean change (95% CI) 2.96 (-1.82, 7.75), d = 0.36) and perceived appearance (mean change (95% CI) 0.32 (-0.25, 0.86), d = 0.35), were observed for the RAP group. Mean feeling state scores improved from preworkout to postworkout in both HIIT conditions, with significant results for the AEP (P = 0.001). CONCLUSIONS: This study highlights the potential of embedding HIIT within the school day for improving cognitive and mental health among adolescents. PMID- 27187099 TI - Neutrophil Depletion Attenuates Muscle Injury after Exhaustive Exercise. AB - PURPOSE: The infiltration of macrophages in skeletal muscle during exhaustive exercise promotes inflammation, myofiber lesion, and muscle injury. Although neutrophils upregulate macrophage infiltration in skeletal muscles during exercise, the role of neutrophils in promoting muscle injury after exhaustive exercise remains unclear. In this study, we investigated the effects of preexercise neutrophil depletion with antineutrophil antibody treatment on muscle injury, inflammation, and macrophage infiltration after exhaustive exercise. METHODS: Male C57BL/6J mice were randomly assigned to four groups, namely, sedentary with control antibody (n = 10), sedentary with antineutrophil antibody (n = 10), exhaustive exercise with control antibody (n = 10), and exhaustive exercise with antineutrophil antibody (n = 10). The mice were given intraperitoneal injection of the antineutrophil antibody (anti-Ly-6G, clone 1A8) or the control antibody (anti-Ly-6G, clone 2A3), and remained inactive or performed exhaustive exercise on a treadmill 48 h after the injection. Twenty four hours after the exhaustive exercise, the gastrocnemius muscles were removed for histological and polymerase chain reaction (PCR) analyses. Infiltration of neutrophils and macrophages was evaluated with Ly-6G and F4/80 immunohistochemistry staining procedures. Muscle fiber injury was detected based on the number of IgG staining fiber. The mRNA expression levels of proinflammatory cytokines and chemokines were evaluated with real-time reverse transcription PCR. RESULTS: Exhaustive exercise increased neutrophil infiltration into the gastrocnemius muscle substantially by 3.1-fold and caused muscle injury, but these effects were markedly suppressed by preexercise treatment with antineutrophil antibody (neutrophil infiltration, 0.42-fold, and muscle injury, 0.18-fold). Treatment with antineutrophil antibody also decreased macrophage infiltration (0.44-fold) and mRNA expression of tumor necrosis factor-alpha (0.55 fold) and interleukin-6 (0.51-fold) in the skeletal muscle after exhaustive exercise. CONCLUSION: These results suggest that neutrophils contribute to exacerbating muscle injury by regulating inflammation through the induction of macrophage infiltration. PMID- 27187100 TI - Fitness during Breast Cancer Treatment and Recovery in an Athlete: A Case Study. AB - PURPOSE: This is a case study of an aerobically trained, multisport, female athlete (age = 39) diagnosed with stage IIIc human epidermal growth factor receptor 2 positive breast cancer. The focus of the study is on measures of cardiorespiratory fitness (VO2peak) through the course of cancer therapy. METHODS: A symptom-limited cardiopulmonary exercise tolerance test was performed to determine VO2peak. The tests were performed at five different time points: 1) at diagnosis of breast cancer and before initiating chemotherapy, 2) after completion of chemotherapy (5 months postdiagnosis), 3) 2.5 months after bilateral mastectomy surgery (9 months postdiagnosis), 4) immediately after radiation therapy (11 months postdiagnosis), and 5) recovery (32 months postdiagnosis). RESULTS: At diagnosis and before initiating chemotherapy, VO2peak was 50.1 mL O2.min.kg. The most precipitous decline in fitness, approximately 14%, was observed from initial diagnosis through the completion of chemotherapy. The subject regained 9% of her fitness after chemotherapy, despite an intervening mastectomy surgery. Radiation therapy was associated with an approximately 4% decline in fitness from her postmastectomy surgery value. Ultimately, 32 months after diagnosis and 22 months after the completion of radiation therapy, the subject was able to regain pretreatment fitness levels. CONCLUSION: The results of the case study describe the effects of undergoing extensive breast cancer therapy on measures of VO2peak for a highly aerobically trained, multisport athlete. In this case, exercise training reversed the decrement in measured VO2peak that occurred during cancer therapy. PMID- 27187101 TI - Intensity-Dependent Contribution of Neuromuscular Fatigue after Constant-Load Cycling. AB - PURPOSE: We tested the hypothesis that central and peripheral fatigue after constant-load cycling exercise would vary with exercise intensity and duration. METHODS: Twelve well-trained male cyclists (VO2max, 4.49 +/- 0.35 L.min) completed three constant-load cycling trials to the limit of tolerance in a randomized crossover design. Exercise intensities were set according to the respiratory responses to a preliminary ramp test to elicit cardiorespiratory and metabolic responses consistent with exercise in the severe and heavy exercise domains: 1) at power at VO2max (S+, 379 +/- 31 W), 2) at 60% of the difference between gas exchange threshold and VO2max (S-, 305 +/- 23 W), and 3) at the respiratory compensation point (RCP, 254 +/- 26 W). Pre- and postexercise twitch responses from the quadriceps to the electrical stimulation of the femoral nerve and magnetic stimulation of the motor cortex were recorded to assess neuromuscular and corticospinal function, respectively. RESULTS: Exercise time was 3.14 +/- 0.59, 11.11 +/- 1.86, and 42.14 +/- 9.09 min for S+, S-, and RCP, respectively. All trials resulted in similar reductions in maximum voluntary force (P = 0.61). However, the degree of peripheral fatigue varied in an intensity-dependent manner, with greater reductions in potentiated twitch force after S+ (-33% +/- 9%) compared with both S- (-16% +/- 9%, P < 0.001) and RCP trials (-11% +/- 9%, P < 0.001) and greater after S- compared with RCP (P < 0.05). For central fatigue, this trend was reversed, with smaller reductions in voluntary activation after S+ compared with RCP (-2.7% +/- 2.2% vs -9.0% +/- 4.7%, P < 0.01). CONCLUSION: These data suggest the magnitude of peripheral and central fatigue after locomotor cycling exercise is exacerbated with exercise intensity and duration, respectively. PMID- 27187102 TI - Head Impact Biomechanics in Women's College Soccer. AB - INTRODUCTION: There are limited nonlaboratory soccer head impact biomechanics data. This is surprising given soccer's global popularity. Epidemiological data suggest that female college soccer players are at a greater concussion injury risk than their male counterparts. Therefore, the purposes of our study were to quantify head impact frequency and magnitude during women's soccer practices and games in the National Collegiate Athletic Association and to characterize these data across event type, playing position, year on the team, and segment of game (first and second halves). METHODS: Head impact biomechanics were collected from female college soccer players (n = 22; mean +/- SD age = 19.1 +/- 0.1 yr, height = 168.0 +/- 3.5 cm, mass = 63.7 +/- 6.0 kg). We employed a helmetless head impact measurement device (X2 Biosystems xPatch) before each competition and practice across a single season. Peak linear and rotational accelerations were categorized based on impact magnitude and subsequently analyzed using appropriate nonparametric analyses. RESULTS: Overall, women's college soccer players experience approximately seven impacts per 90 min of game play. The overwhelming majority (~90%) of all head impacts were categorized into our mildest linear acceleration impact classification (10g-20g). Interestingly, a higher percentage of practice impacts in the 20g-40g range compared with games (11% vs 7%) was observed. CONCLUSION: Head impact biomechanics studies have provided valuable insights into understanding collision sports and for informing evidence-based rule and policy changes. These have included changing the football kickoff, ice hockey body checking ages, and head-to-head hits in both sports. Given soccer's global popularity, and the growing public concern for the potential long-term neurological implications of collision and contact sports, studying soccer has the potential to impact many athletes and the sports medicine professionals caring for them. PMID- 27187103 TI - Leisure-Time Physical Activity and the Risk of Suspected Bacterial Infections. AB - INTRODUCTION: The risk of upper respiratory tract viral infections is reduced with increased physical activity, but little information is available regarding bacterial infections. We examined the relationship between leisure-time physical activity and suspected bacterial infections. METHODS: Information on leisure-time physical activity was obtained from the 2007 and 2010 North Denmark Region Health Surveys of 18,874 Danes and linked to data from nationwide administrative registries. Suspected bacterial infections were determined based on filled prescriptions for antibiotics. Adjusted estimates were calculated using logistic regression models. RESULTS: During a 1-yr follow-up, 5368 participants filled at least one antibiotic prescription. There was a statistically significant difference between physical activity level and filling any antibiotic prescriptions among women (P = 0.003) but not among men (P = 0.191). Logistic regression analysis showed that compared with sedentary behavior, all levels of leisure-time physical activities lowered the likelihood of filling an antibiotic prescription. However, after multivariable adjustments, only estimates of low physical activity were significant (odds ratio [OR] = 0.90, 95% confidence interval [CI] = 0.82; 0.99). Multivariable adjusted subgroup analyses of suspected cystitis showed a decreased likelihood of engaging in low (OR = 0.79, 95% CI = 0.65-0.95) and moderate (OR = 0.68, 95% CI = 0.54-0.87) physical activity. CONCLUSION: Low leisure-time physical activity is associated with a statistically significant 10% lower risk of suspected bacterial infections during a 1-yr follow-up compared with sedentary behavior. Further, low and moderate levels of physical activity were associated with the statistically significant reduction of suspected cystitis. No reduction in suspected respiratory tract infections was statistically significant and associated with physical activity compared with sedentary behavior. PMID- 27187104 TI - The Relation of Arm Exercise Peak Heart Rate to Stress Test Results and Outcome. AB - PURPOSE: Arm exercise is an alternative to pharmacologic stress testing for >50% of patients unable to perform treadmill exercise, but no data exist regarding the effect of attained peak arm exercise heart rate on test sensitivity. Thus, the purpose of this investigation was to characterize the relationship of peak arm exercise heart rate responses to abnormal stress test findings, coronary revascularization, and mortality in patients unable to perform leg exercise. METHODS: From 1997 until 2002, arm cycle ergometer stress tests were performed in 443 consecutive veterans age 64.1 yr (11.0 yr) (mean (SD)), of whom 253 also underwent myocardial perfusion imaging (MPI). Patients were categorized by frequency distributions of quartiles of percentage age-predicted peak heart rate (APPHR), heart rate reserve (HRR), and peak heart rate-systolic blood pressure product (PRPP). Exercise-induced ST-segment depression, abnormal MPI findings, coronary revascularization, and 12.0-yr (1.3 yr) Kaplan-Meier all-cause and cardiovascular mortality plots were then characterized by quartiles of APPHR, HRR, and PRPP. RESULTS: A reduced frequency of abnormal arm exercise ECG results was associated only with the lowest quartile of APPHR (<=69%) and HRR (<=43%), whereas higher frequency of abnormal MPI findings exhibited an inverse relationship trend with lower APPHR (P = 0.10) and HRR (P = 0.12). There was a strong inverse association of APPHR, HRR, and PRPP with all-cause (all P <= 0.01) and cardiovascular (P < 0.05) mortality. The frequency of coronary revascularization was unrelated to APPHR or HRR. CONCLUSIONS: Arm exercise ECG stress test sensitivity is only reduced at <=69% APPHR or <=43% HRR, whereas arm exercise MPI sensitivity and referral for coronary revascularization after arm exercise stress testing are not adversely affected by even a severely blunted peak heart rate. However, both all-cause mortality and cardiovascular mortality are strongly and inversely related to APPHR and HRR. PMID- 27187106 TI - Synthesis of Organized Layered Carbon by Self-Templating of Dithiooxamide. AB - An unusual small molecule, dithiooxamide is used to produce nanostructured carbon via direct pyrolysis. The carbon shows a unique 2D-layer assembled structure and is in situ dual-heteroatom (N and S)-doped, meanwhile having relatively high surface area. These carbon materials can be further decorated with inorganic parts via a precomplexing approach. The functionalized carbon and the hybrid nanomaterials demonstrate remarkable performance for lithium-ion storage. PMID- 27187105 TI - Ischemic Preconditioning and Repeated Sprint Swimming: A Placebo and Nocebo Study. AB - PURPOSE: Ischemic preconditioning (IPC) has been shown to improve performance of exercises lasting 10-90 s (anaerobic) and more than 90 s (aerobic). However, its effect on repeated sprint performance has been controversial, placebo effect has not been adequately controlled, and nocebo effect has not been avoided. Thus, the IPC effect on repeated sprint performance was investigated using a swimming task and controlling placebo/nocebo effects. METHODS: Short-distance university swimmers were randomized to two groups. One group (n = 15, 24 +/- 1 yr [mean +/- SEM]) was exposed to IPC (ischemia cycles lasted 5 min) and control (CT) (no ischemia); another (n = 15, 24 +/- 1 yr) to a placebo intervention (SHAM) (ischemia cycles lasted 1 min) and CT. Seven subjects crossed over groups. Subjects were informed IPC and SHAM would improve performance compared with CT and would be harmless despite circulatory occlusion sensations. The swimming task consisted of six 50-m all-out efforts repeated every 3 min. RESULTS: IPC, in contrast with SHAM, reduced worst sprint time (IPC, 35.21 +/- 0.73 vs CT, 36.53 +/- 0.72 s; P = 0.04) and total sprints time (IPC, 203.7 +/- 4.60 vs CT, 206.03 +/- 4.57 s; P = 0.02), moreover augmented swimming velocity (IPC, 1.45 +/- 0.03 vs CT, 1.44 +/- 0.03 m.s; P = 0.049). Six of seven subjects who crossed over groups reduced total sprints time with IPC versus SHAM (delta = -3.95 +/- 1.49 s, P = 0.09). Both IPC and SHAM did not change blood lactate concentration (P = 0.20) and perceived effort (P = 0.22). CONCLUSION: IPC enhanced repeated sprint swimming performance in university swimmers, whereas a placebo intervention did not. PMID- 27187107 TI - Searching for the philosopher's stone: promising links between meditation and brain preservation. AB - In the context of an aging population and increased prevalence of dementia and other neurodegenerative diseases, developing strategies to decrease the negative effects of aging is imperative. The scientific study of meditation as a potential tool to downregulate processes implicated in brain aging is an emerging field, and a growing body of research suggests that mindfulness practices are beneficial for cerebral resilience. Adding further evidence to this notion, an increasing number of imaging studies report effects of meditation on brain structure that are consistent with our understanding of neuroprotection. Here, we review the published findings in this field of research addressing the question of whether meditation diminishes age-related brain degeneration. Altogether, although analyses are still sparse and based on cross-sectional data, study outcomes suggest that meditation might be beneficial for brain preservation-both with respect to gray and white matter-possibly by slowing down the natural (age related) decrease of brain tissue. Nevertheless, it should also be recognized that, until robust longitudinal data become available, there is no evidence for causation between meditation and brain preservation. This review includes a comprehensive commentary on limitations of the existing research and concludes with implications and directions for future studies. PMID- 27187109 TI - Corrigendum. PMID- 27187108 TI - Chronic pudendal neuromodulation using an implantable microstimulator improves voiding function in diabetic rats. AB - Objective: Few studies have investigated the feasibility of using chronic pudendal neuromodulation for improving voiding function in patients with diabetes who are also experiencing urinary retention. The present study investigated the effects of chronic electrical stimulation (ES) of the sensory branch of the pudendal nerve on voiding function in diabetic rats. Approach: A custom-made implantable microstimulation system was designed and manufactured for chronic implantation in normal control (NC) and diabetic rats. After three or six weeks of pudendal neuromodulation, the intravesical pressure, external urethral sphincter electromyograms (EUS-EMGs), and urine flow rate (UFR) of all rats were simultaneously recorded to assess the effects of chronic pudendal ES on voiding function. Morphological changes in pudendal axons were assessed through hematoxylin and eosin (H&E) staining. Significance: This study demonstrated the feasibility of using chronic pudendal neuromodulation for improving voiding function in diabetic rats. These results may facilitate the development of an advanced neural prosthesis for restoring bladder function in clinical settings. PMID- 27187110 TI - Molecular-Based Theory for Electron-Transfer Reorganization Energy in Solvent Mixtures. AB - Using statistical-field techniques, we develop a molecular-based dipolar self consistent-field theory (DSCFT) for charge solvation in liquid mixtures under equilibrium and nonequilibrium conditions, and apply it to compute the solvent reorganization energy of electron-transfer reactions. In addition to the nonequilibrium orientational polarization, the reorganization energy in liquid mixtures is also determined by the out-of-equilibrium solvent composition around the reacting species due to preferential solvation. Using molecular parameters that are readily available, the DSCFT naturally accounts for the dielectric saturation effect and the spatially varying solvent composition in the vicinity of the reacting species. We identify three general categories of binary solvent mixtures, classified by the relative optical and static dielectric permittivities of the solvent components. Each category of mixture is shown to produce a characteristic local solvent composition profile in the vicinity of the reacting species, which gives rise to the distinctive composition dependence of the reorganization energy that cannot be predicted using the dielectric permittivities of the homogeneous solvent mixtures. PMID- 27187111 TI - Usefulness of radiological findings for predicting cochlear implantation outcomes in children with cochlear nerve deficiency: a pilot study. AB - CONCLUSION: Children with CND received limited benefits from CIs and their results varied. The size of the vestibulocochlear nerve relative to the facial nerve could potentially be used as a predicator for CI outcomes in children with CND. OBJECTIVE: This study aimed to (1) retrospectively review the outcomes of cochlear implants (CIs) in children with cochlear nerve deficiency (CND) and (2) evaluate the clinical usefulness of radiological findings as predictors for post implantation outcomes. METHODS: Study participants included 10 children with bilateral CND and profound sensorineural hearing loss. The preoperative magnetic resonance imaging and temporal bone computed tomography scans were evaluated. Auditory processing capability and speech perception performance were measured with Categories of Auditory Performance (CAP) and Speech Intelligibility Rating (SIR) scales. Aided hearing thresholds with CI were measured. The relationships between CI outcomes and the sizes of vestibulocochlear nerve and cochlear nerve canal (CNC) were analysed. RESULTS: Although post-operative CAP scores and hearing thresholds significantly improved in children with CND, their results were worse than those measured in implanted children with normal cochlear nerve. No significant correlation was found between the CI outcomes and the vestibulocochlear nerve diameters or the CNC diameters in children with CND. However, children with larger vestibulocochlear-nerve-to-facial-nerve-ratios got better results. PMID- 27187113 TI - Severe Radiation Necrosis Successfully Treated With Bevacizumab in an Infant with Low-Grade Glioma and Tumor-Associated Intractable Trigeminal Neuralgia. AB - We present a unique case of radiation necrosis in a child with brain stem low grade glioma (LGG) presenting with trigeminal neuralgia. Despite extensive therapies, severe pain persisted. She received proton beam radiation with significant improvement. However, she developed radiation necrosis and hydrocephalus. Despite surgical correction of hydrocephalus, the patient remained critically ill. She was treated with dexamethasone and bevacizumab with rapid clinical improvement. Subsequent MRIs revealed almost complete resolution of the necrosis. This case illustrates the successful treatment of trigeminal neuralgia with radiation and a rare case of radiation necrosis in an LGG successfully treated with bevacizumab and dexamethasone. PMID- 27187114 TI - Hospital characteristics and 30-day all-cause readmission rates. AB - BACKGROUND: The Centers for Medicare and Medicaid Services (CMS) publicly reports hospital-wide all-cause readmission rates, which are key indicators of quality and waste. Understanding hospital characteristics that are associated with lower readmission rates is important. OBJECTIVES: The main objective of this article is to identify hospital characteristics associated with lower readmission rates. Specifically, we focus on the relationship between hospitalist staffing levels, the level of physician integration, and physician ownership with hospital-wide all-cause readmissions. METHODS: We rely on data from CMS, American Hospital Association Annual Survey Database, and Area Health Resource File. We use ordinary least square regression to assess the association between readmission rates and hospitalist staffing levels, physician integration, physician ownership, and the presence of a medical home model, while controlling for key organizational and market factors such as registered nurse (RN) staffing levels and competition. RESULTS: Higher hospitalist staffing levels, the fully integrated physician model, and physician ownership were associated with lower readmission rates. The addition of 1 hospitalist per general and surgical bed was associated with a 0.77 percentage-points decrease in adjusted 30-day all-cause readmission rates. Fully integrated hospitals had adjusted 30-day all-cause readmission rates 0.09 percentage points lower than non-fully integrated hospitals, and hospitals partially or fully owned by physicians had adjusted readmission rates 0.36 percentage points lower than non-physician-owned hospitals. CONCLUSIONS: Hospitals should focus on modifiable organizational factors that influence patient outcomes such as hospitalist and RN staffing levels and explore hospital-physician arrangements that result in the greatest alignment between hospital and physician incentives. Journal of Hospital Medicine 2016;11:682-687. (c) 2016 Society of Hospital Medicine. PMID- 27187112 TI - Nuclear Magnetic Resonance Structure of a Major Lens Protein, Human gammaC Crystallin: Role of the Dipole Moment in Protein Solubility. AB - A hallmark of the crystallin proteins is their exceptionally high solubility, which is vital for maintaining the high refractive index of the eye lens. Human gammaC-crystallin is a major gamma-crystallin whose mutant forms are associated with congenital cataracts but whose three-dimensional structure is not known. An earlier study of a homology model concluded that human gammaC-crystallin has low intrinsic solubility, mainly because of the atypical magnitude and fluctuations of its dipole moment. On the contrary, the high-resolution tertiary structure of human gammaC-crystallin determined here shows unequivocally that it is a highly soluble, monomeric molecule in solution. Notable differences between the orientations and interactions of several side chains are observed upon comparison to those in the model. No evidence of the pivotal role ascribed to the effect of dipole moment on protein solubility was found. The nuclear magnetic resonance structure should facilitate a comprehensive understanding of the deleterious effects of cataract-associated mutations in human gammaC-crystallin. PMID- 27187117 TI - Hibernating Squirrels: SIRTin Clues for Organ Protection after Ischemia Reperfusion. PMID- 27187120 TI - Is the "Triple Low" Association with Death Statistically Valid or Reflective of Clinical Practice? PMID- 27187119 TI - Proteomic Profiling Reveals Adaptive Responses to Surgical Myocardial Ischemia Reperfusion in Hibernating Arctic Ground Squirrels Compared to Rats. AB - BACKGROUND: Hibernation is an adaptation to extreme environments known to provide organ protection against ischemia-reperfusion (I/R) injury. An unbiased systems approach was utilized to investigate hibernation-induced changes that are characteristic of the hibernator cardioprotective phenotype, by comparing the myocardial proteome of winter hibernating arctic ground squirrels (AGS), summer active AGS, and rats subjected to I/R, and further correlating with targeted metabolic changes. METHODS: In a well-defined rodent model of I/R by deep hypothermic circulatory arrest followed by 3 or 24 h of reperfusion or sham, myocardial protein abundance in AGS (hibernating summer active) and rats (n = 4 to 5/group) was quantified by label-free proteomics (n = 4 to 5/group) and correlated with metabolic changes. RESULTS: Compared to rats, hibernating AGS displayed markedly reduced plasma levels of troponin I, myocardial apoptosis, and left ventricular contractile dysfunction. Of the 1,320 rat and 1,478 AGS proteins identified, 545 were differentially expressed between hibernating AGS and rat hearts (47% up-regulated and 53% down-regulated). Gene ontology analysis revealed down-regulation in hibernating AGS hearts of most proteins involved in mitochondrial energy transduction, including electron transport chain complexes, acetyl CoA biosynthesis, Krebs cycle, glycolysis, and ketogenesis. Conversely, fatty acid oxidation enzymes and sirtuin-3 were up-regulated in hibernating AGS, with preserved peroxisome proliferator-activated receptor-alpha activity and reduced tissue levels of acylcarnitines and ceramides after I/R. CONCLUSIONS: Natural cardioprotective adaptations in hibernators involve extensive metabolic remodeling, featuring increased expression of fatty acid metabolic proteins and reduced levels of toxic lipid metabolites. Robust up-regulation of sirtuin-3 suggests that posttranslational modifications may underlie organ protection in hibernating mammals. PMID- 27187121 TI - Not Really Triple Low? PMID- 27187122 TI - In Reply. PMID- 27187123 TI - All Work Hours Are Not Equal. PMID- 27187124 TI - In Reply. PMID- 27187125 TI - Specific or Nonspecific? There Is Very Little Light at the End of the Tunnel. PMID- 27187127 TI - Ultrasonographic Appearance of the Cricothyroid Membrane. PMID- 27187126 TI - In Reply. PMID- 27187128 TI - In Reply. PMID- 27187130 TI - In Reply. PMID- 27187129 TI - Effectiveness versus Efficacy of Calabadion and Sugammadex for Nondepolarizing Neuromuscular Blocking Agent Reversal. PMID- 27187131 TI - Should Deidentified Case Data Be Treated as Independent Data Points? PMID- 27187132 TI - In Reply. PMID- 27187143 TI - The effect of clinical setting on the unstimulated salivary flow rate. AB - OBJECTIVE: Unstimulated whole saliva (UWS) sialometry uses the spitting method to assess occurrence of hyposalivation. This study compares the UWS flow rates in volunteers sitting in a laboratory or in a clinical setting, in order to evaluate the influence of environment on salivary secretion. DESIGN: 25 healthy volunteers were recruited and divided into two groups to perform UWS sialometry under the two different settings (T1). Eleven weeks later, the participants repeated the same test (T2). At a unique time point and under the clinical setting, 18 patients complaining of xerostomia also performed the UWS sialometry; these values were used as control to corroborate findings. RESULTS: Different scenarios - laboratory one vs. clinical one - did not affect measurements of mean UWS flow rates. Both intra- and inter-individual variabilities, reported as standard error of the mean (SEM) and within-subject variance (WSV), resulted below the threshold of 0.1g/min. A significant difference was found between UWS flow rates from healthy volunteers and those from patients with xerostomia (p<0.05). Test/retest reliability showed a moderate correlation of datasets collected at the two time points from healthy volunteers (T1 vs. T2, 11 weeks later): under laboratory and clinical settings, Pearson's coefficients of correlation were r=0.62 and r=0.32, respectively. CONCLUSIONS: Type of environment did not influence UWS sialometry via spitting method, which appeared reliable for intra-day analysis of the salivary flow rate, although prone to physiological variations over time. PMID- 27187145 TI - Proteomic interrogation of the gut microbiota: potential clinical impact. PMID- 27187146 TI - Extension of the stability of anticancer drugs in pharmaceutical practice. PMID- 27187147 TI - Forget me not. AB - An enzyme called PKM zeta may have a role in long-term memory after all. PMID- 27187151 TI - The Flint Water Crisis Confirms That U.S. Drinking Water Needs Improved Risk Management. PMID- 27187148 TI - Ca(2+) entry into neurons is facilitated by cooperative gating of clustered CaV1.3 channels. AB - CaV1.3 channels regulate excitability in many neurons. As is the case for all voltage-gated channels, it is widely assumed that individual CaV1.3 channels behave independently with respect to voltage-activation, open probability, and facilitation. Here, we report the results of super-resolution imaging, optogenetic, and electrophysiological measurements that refute this long-held view. We found that the short channel isoform (CaV1.3S), but not the long (CaV1.3L), associates in functional clusters of two or more channels that open cooperatively, facilitating Ca(2+) influx. CaV1.3S channels are coupled via a C terminus-to-C-terminus interaction that requires binding of the incoming Ca(2+) to calmodulin (CaM) and subsequent binding of CaM to the pre-IQ domain of the channels. Physically-coupled channels facilitate Ca(2+) currents as a consequence of their higher open probabilities, leading to increased firing rates in rat hippocampal neurons. We propose that cooperative gating of CaV1.3S channels represents a mechanism for the regulation of Ca(2+) signaling and electrical activity. PMID- 27187152 TI - The interaction of personality profile and lactation differs between mothers of late preterm and term neonates. AB - Late preterm birth, a rapidly growing segment of premature deliveries, has the potential to cause deleterious effects on women's psycho-emotional experience of labor and the establishment of successful lactation. We compared personality traits by the Luscher Color Test, the mother-to-infant bonding attitudes by the Mother-to-Infant Bonding Scale (MIBS) and lactation outcome, between mothers of late preterm and at term infants. Our results indicated that mothers idealize their condition and wish to enjoy this magic and extraordinary time in spite of feeling stressed. However, late preterm mothers feel too sad and distressed to relax in their own space after the premature birth event. In addition, their total MIBS score (mean +/- SD) was significantly higher (1.364 versus 0.581; p 0.026), as related subscales: Dislike (p 0.005) and Disappointed (p 0.012). Finally, they significantly reduced breastfeeding rates from discharge (p < 0.0001), to the first (p < 0.001), the third (p = 0.002) and sixth postnatal month (p = 0.0002). We concluded that there is a relation between unconscious deep stress along with bonding limits of late preterm new mothers and impaired breastfeeding initiation and duration. PMID- 27187149 TI - A feedback amplification loop between stem cells and their progeny promotes tissue regeneration and tumorigenesis. AB - Homeostatic renewal of many adult tissues requires balanced self-renewal and differentiation of local stem cells, but the underlying mechanisms are poorly understood. Here we identified a novel feedback mechanism in controlling intestinal regeneration and tumorigenesis in Drosophila. Sox21a, a group B Sox protein, is preferentially expressed in the committed progenitor named enteroblast (EB) to promote enterocyte differentiation. In Sox21a mutants, EBs do not divide, but cannot differentiate properly and have increased expression of mitogens, which then act as paracrine signals to promote intestinal stem cell (ISC) proliferation. This leads to a feedback amplification loop for rapid production of differentiation-defective EBs and tumorigenesis. Notably, in normal intestine following damage, Sox21a is temporally downregulated in EBs to allow the activation of the ISC-EB amplification loop for epithelial repair. We propose that executing a feedback amplification loop between stem cells and their progeny could be a common mechanism underlying tissue regeneration and tumorigenesis. PMID- 27187153 TI - First evaluation of neustonic microplastics in Black Sea waters. AB - The Black Sea has a high risk of plastic pollution given the high river discharge of several industrialized countries into this semi-enclosed sea. Here, for the first time, the occurrence and distribution of microplastics are reported for the Black Sea. Microplastics were assessed from zooplankton samples taken during two cruises along the south eastern coast of the Black Sea in the November of 2014 and February of 2015. In each cruise neuston samples were collected at 12 stations using a WP2 net with 200 MUm mesh. Microplastics (0.2-5 mm) were found in 92% of the samples. The primary shapes were fibres (49.4%) followed by plastic films (30.6%) and fragments (20%), and no micro beads were found. Average microplastic concentration in November (1.2 +/- 1.1 * 10(3) par. m(-3)) was higher than in February (0.6 +/- 0.55 * 10(3) par. m(-3)). Reduced concentrations in February were possibly caused by increased mixing. The highest concentrations of microplastics were observed in offshore stations during November sampling. The heterogeneous spatial distribution (0.2 * 10(3)-3.3 * 10(3) par. m(-3) for all samples) and accumulation in some stations could be associated to transport and retention mechanisms linked with wind and the dynamics of the rim current, as well by different sources of plastic. There were no statistically significant differences in MP concentration between sampling stations and sampling periods (t test, p < 0.05).The relatively high microplastic concentrations suggest that Black Sea is a hotspot for microplastic pollution and there is an urgency to understand their origins, transportation and effects on marine life. PMID- 27187150 TI - Compensation for PKMzeta in long-term potentiation and spatial long-term memory in mutant mice. AB - PKMzeta is a persistently active PKC isoform proposed to maintain late-LTP and long-term memory. But late-LTP and memory are maintained without PKMzeta in PKMzeta-null mice. Two hypotheses can account for these findings. First, PKMzeta is unimportant for LTP or memory. Second, PKMzeta is essential for late-LTP and long-term memory in wild-type mice, and PKMzeta-null mice recruit compensatory mechanisms. We find that whereas PKMzeta persistently increases in LTP maintenance in wild-type mice, PKCiota/lambda, a gene-product closely related to PKMzeta, persistently increases in LTP maintenance in PKMzeta-null mice. Using a pharmacogenetic approach, we find PKMzeta-antisense in hippocampus blocks late LTP and spatial long-term memory in wild-type mice, but not in PKMzeta-null mice without the target mRNA. Conversely, a PKCiota/lambda-antagonist disrupts late LTP and spatial memory in PKMzeta-null mice but not in wild-type mice. Thus, whereas PKMzeta is essential for wild-type LTP and long-term memory, persistent PKCiota/lambda activation compensates for PKMzeta loss in PKMzeta-null mice. PMID- 27187156 TI - Editorial: Genomic selection with numerically small reference populations. PMID- 27187154 TI - AR-12 Inhibits Multiple Chaperones Concomitant With Stimulating Autophagosome Formation Collectively Preventing Virus Replication. AB - We have recently demonstrated that AR-12 (OSU-03012) reduces the function and ATPase activities of multiple HSP90 and HSP70 family chaperones. Combined knock down of chaperones or AR-12 treatment acted to reduce the expression of virus receptors and essential glucosidase proteins. Combined knock down of chaperones or AR-12 treatment inactivated mTOR and elevated ATG13 S318 phosphorylation concomitant with inducing an endoplasmic reticulum stress response that in an eIF2alpha-dependent fashion increased Beclin1 and LC3 expression and autophagosome formation. Over-expression of chaperones prevented the reduction in receptor/glucosidase expression, mTOR inactivation, the ER stress response, and autophagosome formation. AR-12 reduced the reproduction of viruses including Mumps, Influenza, Measles, Junin, Rubella, HIV (wild type and protease resistant), and Ebola, an effect replicated by knock down of multiple chaperone proteins. AR-12-stimulated the co-localization of Influenza, EBV and HIV virus proteins with LC3 in autophagosomes and reduced viral protein association with the chaperones HSP90, HSP70, and GRP78. Knock down of Beclin1 suppressed drug induced autophagosome formation and reduced the anti-viral protection afforded by AR-12. In an animal model of hemorrhagic fever virus, a transient exposure of animals to low doses of AR-12 doubled animal survival from ~30% to ~60% and suppressed liver damage as measured by ATL, GGT and LDH release. Thus through inhibition of chaperone protein functions; reducing the production, stability and processing of viral proteins; and stimulating autophagosome formation/viral protein degradation, AR-12 acts as a broad-specificity anti-viral drug in vitro and in vivo. We argue future patient studies with AR-12 are warranted. J. Cell. Physiol. 231: 2286-2302, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27187155 TI - Identification and measurement of staphylococcal enterotoxin-like protein I (SEll) secretion from Staphylococcus aureus clinical isolate. AB - AIMS: Staphylococcus aureus (Staph. aureus) produces a wide variety of staphylococcal enterotoxins (SEs) and staphylococcal enterotoxin-like (SEl) proteins, which are the most causative agents of staphylococcal food poisoning. In contrast to classical SEs (SEA to SEE), the relationship between the novel SEs/SEls (SEG to SElX) and staphylococcal food poisoning is not elucidated. This study is aimed to establish a system to detect staphylococcal enterotoxin-like protein I (SElI) for analysis of staphylococcal food poisoning. METHODS AND RESULTS: SElI was characterized in a Staph. aureus clinical isolate associated with food poisoning; there was an amino acid substitution Thr145Ala compared to previously identified SEI from Staph. aureus 04-02981. Subsequently, SElI was expressed, purified, and the poly- and monoclonal antibodies against it were prepared. Using these antibodies, a highly sensitive sandwich enzyme-linked immunosorbent assay (ELISA) that specifically detected and measured SElI secretion from the Staph. aureus clinical isolate in LB medium, milk and bloodstream was developed. CONCLUSIONS: The ELISA system has been successfully applied for analysing SElI secretion in vivo and in vitro. SIGNIFICANCE AND IMPACT OF THE STUDY: The highly sensitive ELISA should make it attractive for quantifying SElI in food hygiene supervision and clinical diagnosis in near future. PMID- 27187157 TI - Chronic kidney disease in Asia: Protocol for a collaborative overview. AB - AIM: The burden of chronic kidney disease (CKD) is growing rapidly around the world. However, there is limited information on the overall regional prevalence of CKD, as well as the prognostic implications and treatment patterns in Asian region. We have established the Asian Renal Collaboration (ARC) with the goal of consolidating region-wide data regarding CKD. METHODS: This collaborative project will synthesize data and perform meta-analyses of observational studies conducted in Asia. Studies will be identified through a systematic literature search including abstracts, proceedings of meetings, electronic databases such as MEDLINE and EMBASE. Personal enquiry among collaborators and experts in the region will identify additional studies, or other data sources such as registries. Both cross-sectional and longitudinal studies that describe the prevalence of CKD and its complications will be included, as will longitudinal studies that describe important clinical outcomes for people with CKD. Individual participant data will be sought, where possible, from each of the studies included in the collaboration for baseline parameters and subsequent outcomes, in order to maximize flexibility and consistency of data analyses. CONCLUSIONS: This study is an initiative offering a unique opportunity to obtain information about the prevalence and manifestations of CKD in Asia, as well as its risk factors. The ARC will also provide insights into important outcomes including progression of CKD, CKD complications, cardiovascular disease and death. These findings will improve our understanding of kidney disease in Asia, and thus help inform service provision, preventive care and further research across the region. PMID- 27187158 TI - Pyrazinetetracarboxamide: A Duplex Ligand for Palladium(II). AB - Tetraethylpyrazine-2,3,5,6-tetracarboxamide forms a dipalladium(II) complex with acetates occupying the fourth coordination sites of the two bound metal ions. Crystallographic results indicate that the "duplex" dipincer has captured two protons that serve as the counterions. The protons lie between adjacent amide carbonyl groups with very short O...O distances of 2.435(5) A. In the free base, the adjacent carbonyl groups are farther apart, averaging 3.196(3) A. While the dipalladium(II) complexes stack in an ordered stepwise fashion along the a axis, the free base molecules stack on top of each other, with each pincer rotated by about 60 degrees from the one below. PMID- 27187159 TI - Diagnosis and management of symptoms associated with vulvovaginal atrophy: expert opinion on behalf of the Italian VVA study group. AB - Vulvovaginal atrophy (VVA) is a chronic disorder that commonly occurs in postmenopausal women, whose symptoms are recognized among the most frequent and bothersome symptoms associated with menopause. The principal therapeutic goal in managing VVA is to relieve symptoms as well as to restore the vaginal environment to a healthy state. However, despite its high prevalence and negative impact on quality of life, VVA is underreported by women, underrecognized by gynecologists, and therefore, undertreated. In the light of the new development of treatment options for VVA, we here provide an updated expert opinion on the management of VVA. In particular, we strongly recommend that HCPs proactively start an open discussion with their postmenopausal patients about urogenital symptoms. Treatment should be started as early as the first symptoms of VVA occur and should be maintained over time, due to the chronicity of the conditions. Many treatment options are now available and therapy should be individualized, taking the woman's preference in consideration. PMID- 27187162 TI - Role of MRI in the Risk Assessment of Primary Prostate Cancer. AB - A successful paradigm shift toward personalized management strategies for patients with prostate cancer (PCa) is heavily dependent on the availability of noninvasive diagnostic tools capable of accurately establishing the true extent of disease at the time of diagnosis and estimating the risk of subsequent disease progression and related mortality. Although there is still considerable scope for improvement in its diagnostic, predictive, and prognostic capabilities, multiparametric prostate magnetic resonance imaging (MRI) is currently regarded as the imaging modality of choice for local staging of PCa. A negative MRI, that is, the absence of any MRI-visible intraprostatic lesion, has a high negative predictive value for the presence of clinically significant PCa and can substantiate the consideration of active surveillance as a preferred initial management approach. MRI-derived quantitative and semi-quantitative parameters can be utilized to noninvasively characterize MRI-visible prostate lesions and identify those patients who are most likely to benefit from radical treatment, and differentiate them from patients with benign or indolent prostate pathology that may also be visible on MRI. This literature review summarizes current strategies how MRI can be used to determine a tailored management strategy for an individual patient. PMID- 27187160 TI - Platinum Concentration and Pathologic Response to Cisplatin-Based Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer. AB - BACKGROUND: Platinum (Pt)-based chemotherapy is the standard of care for muscle invasive bladder cancer (MIBC). However, resistance is a major limitation. Reduced intratumoral drug accumulation is an important mechanism of platinum resistance. Our group previously demonstrated a significant correlation between tissue Pt concentration and tumor response to Pt-based neoadjuvant chemotherapy (NAC) in lung cancer. We hypothesized that increased Pt concentration in radical cystectomy (RC) specimens would correlate with improved pathologic response to Pt based NAC in MIBC. METHODS: A cohort of 19 clinically annotated, archived, fresh frozen RC specimens from patients with MIBC treated with Pt-based NAC was identified [ypT0 (pathologic complete response, pCR), N = 4; <=ypT1N0M0 (pathologic partial response, pPR), N = 6; >=ypT2 (minimal pathologic response/progression), N = 9)]. RC specimens from 2 patients with MIBC who did not receive NAC and 1 treated with a non-Pt containing NAC regimen were used as negative controls. Total Pt concentration in normal adjacent urothelial tissue and bladder tumors from RC specimens was measured by flameless atomic absorption spectrophotometry. RESULTS: Total Pt concentration in normal urothelium differed by tumor pathologic response (P = 0.011). Specimens with pCR had the highest Pt concentrations compared to those with pPR (P = 0.0095) or no response/progression (P = 0.020). There was no significant difference in Pt levels in normal urothelium and tumor between pPR and no response/progression groups (P = 0.37; P = 0.25, respectively). CONCLUSIONS: Our finding of increased intracellular Pt in RC specimens with pCR following NAC for MIBC compared to those with residual disease suggests that enhanced Pt accumulation may be an important determinant of Pt sensitivity. Factors that modulate intracellular Pt concentration, such as expression of Pt transporters, warrant further investigation as predictive biomarkers of response to Pt-based NAC in MIBC. PMID- 27187163 TI - MR-TRUS Fusion Biopsy. AB - The leading application of multiparametric magnetic resonance imaging (mpMRI) of the prostate is for lesion detection with the intention of tissue sampling (biopsy). Although direct in-bore magnetic resonance (MR)-guided biopsy allows for confirmation of the biopsy site, this can be expensive, time-consuming, and most importantly limited in availability. MR-transrectal ultrasound (MR-TRUS) image fusion targeted biopsy (TBx) allows for lesions identified on MRI to be targeted with the ease, efficiency, and availability of ultrasound.The learning objectives are optimized mpMRI protocol and reporting for image fusion targeted biopsy; methods of TRUS TBx; performance and limitations of MR-TRUS TBx; future improvements and applications. PMID- 27187161 TI - Methylmercury Concentration in Fish and Risk-Benefit Assessment of Fish Intake among Pregnant versus Infertile Women in Taiwan. AB - This study examined methylmercury (MeHg) concentrations in fish, the daily MeHg exposure dose, and the risk-benefit of MeHg, omega-3 polyunsaturated fatty acid (omega-3 PUFA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) related to fish intake among pregnant and infertile women in Taiwan. The measured MeHg concentrations in fish did not exceed the Codex guideline level of 1 mg/kg. Swordfish (0.28 +/- 0.23 mg/kg) and tuna (0.14 +/- 0.13 mg/kg) had the highest MeHg concentrations. The MeHg concentration in the hair of infertile women (1.82 +/- 0.14 mg/kg) was significantly greater than that of pregnant women (1.24 +/- 0.18 mg/kg). In addition, 80% of infertile women and 68% of pregnant women had MeHg concentrations in hair that exceeded the USEPA reference dose (1 mg/kg). The MeHg concentrations in hair were significantly and positively correlated with the estimated daily MeHg exposure dose. Based on the risk-benefit evaluation results, this paper recommends consumption of fish species with a low MeHg concentration and high concentrations of DHA + EPA and omega-3 PUFA (e.g., salmon, mackerel, and greater amberjack). PMID- 27187165 TI - Multiparametric MR Imaging for Detection and Locoregional Staging of Prostate Cancer. AB - Detection and staging of prostate cancer (PCa) based on digital rectal examination, prostate-specific antigen levels, and systematic transrectal ultrasound-guided biopsies show notorious limitations in light of the current needs of PCa management. Multiparametric magnetic resonance imaging (mpMRI) has emerged as a useful noninvasive imaging technique for detection, staging, assessment of aggressiveness, and treatment monitoring of PCa, combining anatomic high-resolution T2-weighted images with functional techniques, such as diffusion weighted imaging and dynamic contrast enhancement evaluation. In this article, the authors review the technical aspects and the current clinical role of mpMRI for detection and locoregional staging of PCa. PMID- 27187166 TI - MRI of Prostate Cancer: Update. PMID- 27187167 TI - Clinical Perspective of Prostate Cancer. AB - Prostate cancer is the most common noncutaneous cancer affecting men today. It largely affects men in the fifth and sixth decade of life. Screening for prostate cancer, though controversial, is still the only way to detect early prostate cancer. Multiple newer options such as blood tests and genetic markers are being used in the clinical domain today to improve cancer detection and avoid unnecessary biopsies. To date, biopsy of the prostate remains the only modality to stratify the grade of cancer. Significant improvements in the imaging technology have improved localizing and detecting the disease. Treatment of prostate cancer is stratified on the basis of the grade and volume of the disease. There are multiple treatment options involved in the management of prostate cancer. Treatment of localized prostate cancer still continues to have very high cure rates and long-term cancer-specific survival rates. PMID- 27187164 TI - Multiparametric Magnetic Resonance Imaging of Recurrent Prostate Cancer. AB - There is growing consensus that multiparametric magnetic resonance imaging (mpMRI) is an effective modality in the detection of locally recurrent prostate cancer after prostatectomy and radiation therapy. The emergence of magnetic resonance (MR)-guided focal therapies, such as cryoablation, high-intensity focused ultrasound, and laser ablation, have made the use of mpMRI even more important, as the normal anatomy is inevitably altered and the detection of recurrence is made more difficult. The aim of this article is to review the utility of mpMRI in detecting recurrent prostate cancer in patients following radical prostatectomy, radiation therapy, and focal therapy and to discuss expected post-treatment mpMRI findings, the varied appearance of recurrent tumors, and their mimics. PMID- 27187168 TI - In-Bore MR-Guided Biopsy Systems and Utility of PI-RADS. AB - A diagnostic dilemma exists in cases wherein a patient with clinical suspicion for prostate cancer has a negative transrectal ultrasound-guided biopsy session. Although transrectal ultrasound-guided biopsy is the standard of care, a paradigm shift is being observed. In biopsy-naive patients and patients with at least 1 negative biopsy session, multiparametric magnetic resonance imaging (MRI) is being utilized for tumor detection and subsequent targeting. Several commercial devices are now available for targeted prostate biopsy ranging from transrectal ultrasound-MR fusion biopsy to in bore MR-guided biopsy. In this review, we will give an update on the current status of in-bore MRI-guided biopsy systems and discuss value of prostate imaging-reporting and data system (PIRADS). PMID- 27187170 TI - Autism and psychosis expressions diametrically modulate the right temporoparietal junction. AB - The mentalizing network is atypically activated in autism and schizophrenia spectrum disorders. While these disorders are considered diagnostically independent, expressions of both can co-occur in the same individual. We examined the concurrent effect of autism traits and psychosis proneness on the activity of the mentalizing network in 24 neurotypical adults while performing a social competitive game. Activations were observed in the paracingulate cortex and the right temporoparietal junction (rTPJ). Autism traits and psychosis proneness did not modulate activity within the paracingulate or the dorsal component of the rTPJ. However, diametric modulations of autism traits and psychosis proneness were observed in the posterior (rvpTPJ) and anterior (rvaTPJ) subdivisions of the ventral rTPJ, which respectively constitute core regions within the mentalizing and attention-reorienting networks. Within the rvpTPJ, increasing autism tendencies decreased activity, and increasing psychosis proneness increased activity. This effect was reversed within the rvaTPJ. We suggest that this results from an interaction between regions responsible for higher level social cognitive processing (rvpTPJ) and regions responsible for domain-general attentional processes (rvaTPJ). The observed diametric modulation of autism tendencies and psychosis proneness of neuronal activity within the mentalizing network highlights the importance of assessing both autism and psychosis expressions within the individual. PMID- 27187172 TI - Beliefs about inhaled corticosteroids: Comparison of community pharmacists, pharmacy technicians and patients with asthma. AB - OBJECTIVES: To compare pharmacists' and pharmacy technicians' perceptions of patients' beliefs regarding inhaled corticosteroids (ICS) with those of patients and to compare the ICS beliefs of pharmacists and technicians with those of patients with asthma. METHODS: 1269 community pharmacies were approached to fill out an online questionnaire; 1952 patients were sent a questionnaire by post. Beliefs (i.e., necessity and concerns) regarding ICS were measured using (an adapted version of) the Beliefs about Medicines Questionnaire (BMQ-specific). Pharmacists and technicians were instructed to fill out the BMQ for themselves, and to fill it out in the way they thought most of their patients would complete it. RESULTS: 136 pharmacists, 90 pharmacy technicians and 161 patients with asthma completed the questionnaire. Pharmacists and technicians thought patients had more concerns about ICS than patients themselves reported (p < 0.0001). They also thought that patients had stronger beliefs in their personal need for ICS than patients reported (p < 0.01). Pharmacists reported lower levels of concerns than patients (p < 0.05) and both providers attributed a higher level of necessity to ICS than patients did (p < 0.0001). CONCLUSION: Pharmacists and technicians overestimate the personal need for treatment as well as the concerns patients with asthma have regarding ICS. They also have, to some extent, stronger positive beliefs about ICS than patients. If pharmacists and technicians expect that patients share their positive views about ICS, they might be less likely to elicit and address patients' doubts and concerns about ICS, which might be relevant for effective ICS treatment and subsequent patient outcomes. PMID- 27187171 TI - Impact of Genetic Polymorphism of methylenetetrahydrofolate reductase C677T on Development of Hyperhomocysteinemia and Related Oxidative Changes in Egyptian beta-Thalassemia Major Patients. AB - BACKGROUND: beta-thalasemia major (beta-TM) patients often suffer from various vascular complications together with increased oxidative stress. Hyperhomocysteinemia (Hhcy) has been defined as a risk factor for these complications. Genetic polymorphism of methylenetetrahydrofolate reductase (MTHFR) C677T has been shown to cause Hhcy particularly in individuals with low B vitamins. However, the status of homocysteine (hcy) in beta-TM has not yet been adequately defined. AIM: To evaluate the genetic polymorphism of MTHFR C677T among beta-TM patients and its prospective contribution to Hhcy and related oxidative changes. SUBJECTS AND METHODS: Genotyping for MTHFR C677T was done by PCR-RFLP technique. Plasma hcy, vitamin B12, folate, malondialdehyde (MDA), total antioxidant capacity (TAC), oxidized low density lipoprotein (oxLDL), total nitric oxide (NOx) and lipid profile were determined in 66 beta-TM patients and 66 control subjects of matched age and sex. RESULTS: The prevalence of MTHFR 677TT genotype was significant among beta-TM patients (12%) compared to (3%) controls (OR = 4.9, 95%CI:1.2-24.2,P = 0.03). A strong association between Hhcy and MTHFR TT genotype was observed (OR = 7.7, 95%CI:2.8-20.9) where all beta-TM patients with TT genotype were hyperhomocystienemic (>= 15 MUmol/l) and having sub-optimal folate level than those with CT or CC genotypes. Hyperhomocystienemic patients have suffered from increased oxidative stress characterized by significant increase in plasma MDA and oxLDL, and a significant reduction of plasma TAC and total NOx. Lipid profile of those patients was severely affected indicated by reduction in HDL and HDL/LDL and elevation in atherogenic index as compared with CC genotype. Other measured parameters were not significantly different among beta-TM patients with different MTHFR genotypes. CONCLUSION: This study suggests that Egyptian beta-TM patients with MTHFR 677TT genotype could be at increasing risk of developing Hhcy particularly with folate deficiency. This state of Hhcy may account potentially for most oxidative changes and atherogenic vascular complications frequently reported in beta-TM patients. PMID- 27187173 TI - Vertically Oriented Arrays of ReS2 Nanosheets for Electrochemical Energy Storage and Electrocatalysis. AB - Transition-metal dichalcogenide (TMD) nanolayers show potential as high performance catalysts in energy conversion and storage devices. Synthetic TMDs produced by chemical-vapor deposition (CVD) methods tend to grow parallel to the growth substrate. Here, we show that with the right precursors and appropriate tuning of the CVD growth conditions, ReS2 nanosheets can be made to orient perpendicular to the growth substrate. This accomplishes two important objectives; first, it drastically increases the wetted or exposed surface area of the ReS2 sheets, and second, it exposes the sharp edges and corners of the ReS2 sheets. We show that these structural features of the vertically grown ReS2 sheets can be exploited to significantly improve their performance as polysulfide immobilizers and electrochemical catalysts in lithium-sulfur (Li-S) batteries and in hydrogen evolution reactions (HER). After 300 cycles, the specific capacity of the Li-S battery with vertical ReS2 catalyst is retained above 750 mA h g(-1), with only ~0.063% capacity decay per cycle, much better than the baseline battery (without ReS2), which shows ~0.184% capacity decay per cycle under the same test conditions. As a HER catalyst, the vertical ReS2 provides very small onset overpotential (<100 mV) and an exceptional exchange-current density (~67.6 MUA/cm(2)), which is vastly superior to the baseline electrode without ReS2. PMID- 27187174 TI - Comparative Effectiveness of Biosimilar, Reference Product and Other Erythropoiesis-Stimulating Agents (ESAs) Still Covered by Patent in Chronic Kidney Disease and Cancer Patients: An Italian Population-Based Study. AB - BACKGROUND: Since 2007 biosimilars of erythropoiesis-stimulating agents (ESAs) are available on the Italian market. Very limited post-marketing data exist on the comparative effectiveness of biosimilar and originator ESAs. AIM: This population-based study was aimed to compare the effects of biosimilars, reference product and other ESAs still covered by patent on hemoglobinemia in chronic kidney disease (CKD) and cancer patients in a Local Health Unit (LHU) from Northern Italy. METHODS: A retrospective cohort study was conducted during the years 2009-2014 using data from Treviso LHU administrative database. Incident ESA users (no ESA dispensing within 6 months prior to treatment start, i.e. index date (ID)) with at least one hemoglobin measurement within one month prior to ID (baseline Hb value) and another measurement between 2nd and 3rd month after ID (follow-up Hb value) were identified. The strength of the consumption (as total number of defined daily dose (DDD) dispensed during the follow-up divided by days of follow-up) and the difference between follow-up and baseline Hb values [delta Hb (DeltaHb)] were evaluated. Based on Hb changes, ESA users were classified as non-responders (DeltaHb<=0 g/dl), responders (02 g/dl). A multivariate ordinal logistic regression model to identify predictors for responsiveness to treatment was performed. All analyses were stratified by indication for use and type of dispensed ESA at ID. RESULTS: Overall, 1,003 incident ESA users (reference product: 252, 25.1%; other ESAs covered by patent: 303, 30.2%; biosimilars: 448, 44.7%) with CKD or cancer were eligible for the study. No statistically significant difference in the amount of dose dispensed during the follow-up among biosimilars, reference product and other ESAs covered by patent was found in both CKD and cancer. After three months from treatment start, all ESAs increased Hb values on average by 2g/dl. No differences in DeltaHb as well as in frequency of non-responders, responders and highly responders among different types of ESAs were observed in both indications of use. Overall, around 15-20% of ESA users were non-responders. Strength of treatment, but no type of dispensed ESAs was found to be predictor of responsiveness to treatment. CONCLUSIONS: No difference on the effects on hemoglobinemia among users of either biosimilars or reference product or ESAs covered by patent was observed in a general population from Northern Italy, despite a comparable dispensed dose of the different ESAs during the first three months of treatment. PMID- 27187176 TI - The Role of Hypothalamic NF-kappaB Signaling in the Response of the HPT-Axis to Acute Inflammation in Female Mice. AB - A large proportion of critically ill patients have alterations in the hypothalamus-pituitary-thyroid (HPT) axis, collectively known as the nonthyroidal illness syndrome. Nonthyroidal illness syndrome is characterized by low serum thyroid hormone (TH) concentrations accompanied by a suppressed central component of the HPT axis and persistent low serum TSH. In hypothalamic tanycytes, the expression of type 2 deiodinase (D2) is increased in several animal models of inflammation. Because D2 is a major source of T3 in the brain, this response is thought to suppress TRH expression in the paraventricular nucleus via increased local bioavailability of T3. The inflammatory pathway component RelA (the p65 subunit of nuclear factor-kappaB) can bind the Dio2 promoter and increases D2 expression after lipopolysaccharide (LPS) stimulation in vitro. We aimed to determine whether RelA signaling in tanycytes is essential for the LPS-induced D2 increase in vivo by conditional elimination of RelA in tanycytes of mice (RelA(ASTKO)). Dio2 and Trh mRNA expression were assessed by quantitative in situ hybridization 8 or 24 hours after saline or LPS injection. At the same time points, we measured pituitary Tshbeta mRNA expression and serum T3 and T4 concentrations. In RelA(ASTKO) mice the LPS-induced increase in Dio2 and decrease in Trh mRNA levels in the hypothalamus were reduced compared with the wild-type littermates, whereas the drop in pituitary Tshbeta expression and in serum TH concentrations persisted. In conclusion, RelA is essential for the LPS-induced hypothalamic D2 increase and TRH decrease. The central changes in the HPT axis are, however, not required for the down-regulation of Tshbeta expression and serum TH concentrations. PMID- 27187177 TI - Glucagon-Like Peptide-2 Requires a Full Complement of Bmi-1 for Its Proliferative Effects in the Murine Small Intestine. AB - The intestinal hormone, glucagon-like peptide-2 (GLP-2), stimulates growth, survival, and function of the intestinal epithelium through increased crypt cell proliferation, and a long-acting analog has recently been approved to enhance intestinal capacity in patients with short bowel syndrome. The goal of the present study was to determine whether GLP-2-induced crypt cell proliferation requires a full complement of B-cell lymphoma Moloney murine leukemia virus insertion region-1 homolog (Bmi-1), using the Bmi-1(eGFP/+) mouse model in comparison with age- and sex-matched Bmi-1(+/+) littermates. Bmi-1 is a member of the polycomb-repressive complex family that promotes stem cell proliferation and self-renewal and is expressed by both stem cells and transit-amplifying (TA) cells in the crypt. The acute (6 h) and chronic (11 d) proliferative responses to long-acting human (Gly(2))GLP-2 in the crypt TA zone, but not in the active or reserve stem cell zones, were both impaired by Bmi-1 haploinsufficiency. Similarly, GLP-2-induced crypt regeneration after 10-Gy irradiation was reduced in the Bmi-1(eGFP/+) animals. Despite these findings, chronic GLP-2 treatment enhanced overall intestinal growth in the Bmi-1(eGFP/+) mice, as demonstrated by increases in small intestinal weight per body weight and in the length of the crypt-villus axis, in association with decreased apoptosis and an adaptive increase in crypt epithelial cell migration rate. The results of these studies therefore demonstrate that a full complement of Bmi-1 is required for the intestinal proliferative effects of GLP-2 in both the physiological and pathological setting, and mediates, at least in part, the proliferation kinetics of cells in the TA zone. PMID- 27187175 TI - Adiponectin Exerts Neurotrophic Effects on Dendritic Arborization, Spinogenesis, and Neurogenesis of the Dentate Gyrus of Male Mice. AB - The hippocampus, a brain region critical for learning, memory and emotional processing, maintains its capacity to undergo structural plasticity throughout life. Hippocampal structural plasticity can be modulated by a number of intrinsic and extrinsic factors. This study investigated the effects of adiponectin, an adipocyte-derived hormone, on dendritic growth, arborization, and spinogenesis in mature granule neurons of the hippocampal dentate gyrus generated during embryonic (early-born) or early postnatal (late-born) stages. We found that adiponectin deficiency reduced dendritic length, branching and spine density of granule neurons. The reduction was more evident in early-born granule neurons than in late-born granule neurons. Intracerebroventricular infusion of adiponectin for 1 week increased of dendritic spines and arbor complexity in late born granule neurons. Moreover, adiponectin deficiency decreased the production of adult-born new granule neurons through suppressing neural progenitor cell proliferation and differentiation, whereas intracerebroventricular adiponectin infusion increased the proliferation of neural progenitor cells in adult dentate gyrus. These results suggest that adiponectin plays an important role in dendritic spine remodeling and neurogenesis in the dentate gyrus. PMID- 27187179 TI - Correction: The Diversity and Geographical Structure of Orientia tsutsugamushi Strains from Scrub Typhus Patients in Laos. AB - [This corrects the article DOI: 10.1371/journal.pntd.0004024.]. PMID- 27187178 TI - A Novel Method to Verify Multilevel Computational Models of Biological Systems Using Multiscale Spatio-Temporal Meta Model Checking. AB - Insights gained from multilevel computational models of biological systems can be translated into real-life applications only if the model correctness has been verified first. One of the most frequently employed in silico techniques for computational model verification is model checking. Traditional model checking approaches only consider the evolution of numeric values, such as concentrations, over time and are appropriate for computational models of small scale systems (e.g. intracellular networks). However for gaining a systems level understanding of how biological organisms function it is essential to consider more complex large scale biological systems (e.g. organs). Verifying computational models of such systems requires capturing both how numeric values and properties of (emergent) spatial structures (e.g. area of multicellular population) change over time and across multiple levels of organization, which are not considered by existing model checking approaches. To address this limitation we have developed a novel approximate probabilistic multiscale spatio-temporal meta model checking methodology for verifying multilevel computational models relative to specifications describing the desired/expected system behaviour. The methodology is generic and supports computational models encoded using various high-level modelling formalisms because it is defined relative to time series data and not the models used to generate it. In addition, the methodology can be automatically adapted to case study specific types of spatial structures and properties using the spatio-temporal meta model checking concept. To automate the computational model verification process we have implemented the model checking approach in the software tool Mule (http://mule.modelchecking.org). Its applicability is illustrated against four systems biology computational models previously published in the literature encoding the rat cardiovascular system dynamics, the uterine contractions of labour, the Xenopus laevis cell cycle and the acute inflammation of the gut and lung. Our methodology and software will enable computational biologists to efficiently develop reliable multilevel computational models of biological systems. PMID- 27187181 TI - Fetal brain imaging in isolated congenital heart defects - a systematic review and meta-analysis. AB - Congenital heart defects (CHDs) are associated with neurodevelopmental (ND) delay. This study aims to assess evidence for impaired prenatal brain development, in fetuses with CHD. A systematical search was performed, and 34 studies evaluating the fetal brain [magnetic resonance imaging (MRI) or ultrasound] in isolated CHD were included (1990-2015). Data regarding cerebral abnormalities, head circumference growth and middle cerebral artery flow were extracted. Prenatal MRI was studied in ten articles (445 fetuses), resulting in a pooled prevalence of 18% (95%CI -6%; 42%) for combined structural and acquired cerebral abnormalities. Prenatal head circumference was studied in 13 articles (753 fetuses), resulting in a pooled z-score of -0.51 (95%CI -0.84; -0.18). Doppler was studied in 21 articles (1412 fetuses), resulting in a lower middle cerebral artery pulsatility index (z-score -0.70 95%CI -0.99; -0.41) in left sided CHD only. We conclude that prenatal MRI and ultrasound demonstrate brain abnormalities, delay in head growth and brainsparing in subgroups of CHD. However, large MRI studies are scarce, and ultrasound data are biased towards severe and left-sided CHD. Long-term follow-up studies correlating prenatal findings with postnatal ND outcome are limited, and data are lacking to support counseling families regarding ND outcome based on prenatal findings suggestive of altered brain development. (c) 2016 John Wiley & Sons, Ltd. PMID- 27187180 TI - A Miniaturized Screen of a Schistosoma mansoni Serotonergic G Protein-Coupled Receptor Identifies Novel Classes of Parasite-Selective Inhibitors. AB - Schistosomiasis is a tropical parasitic disease afflicting ~200 million people worldwide and current therapy depends on a single drug (praziquantel) which exhibits several non-optimal features. These shortcomings underpin the need for next generation anthelmintics, but the process of validating physiologically relevant targets ('target selection') and pharmacologically profiling them is challenging. Remarkably, even though over a quarter of current human therapeutics target rhodopsin-like G protein coupled receptors (GPCRs), no library screen of a flatworm GPCR has yet been reported. Here, we have pharmacologically profiled a schistosome serotonergic GPCR (Sm.5HTR) implicated as a downstream modulator of PZQ efficacy, in a miniaturized screening assay compatible with high content screening. This approach employs a split luciferase based biosensor sensitive to cellular cAMP levels that resolves the proximal kinetics of GPCR modulation in intact cells. Data evidence a divergent pharmacological signature between the parasitic serotonergic receptor and the closest human GPCR homolog (Hs.5HTR7), supporting the feasibility of optimizing parasitic selective pharmacophores. New ligands, and chemical series, with potency and selectivity for Sm.5HTR over Hs.5HTR7 are identified in vitro and validated for in vivo efficacy against schistosomules and adult worms. Sm.5HTR also displayed a property resembling irreversible inactivation, a phenomenon discovered at Hs.5HTR7, which enhances the appeal of this abundantly expressed parasite GPCR as a target for anthelmintic ligand design. Overall, these data underscore the feasibility of profiling flatworm GPCRs in a high throughput screening format competent to resolve different classes of GPCR modulators. Further, these data underscore the promise of Sm.5HTR as a chemotherapeutically vulnerable node for development of next generation anthelmintics. PMID- 27187183 TI - Penile ulcers complicating systemic AL amyloidosis: a case report. PMID- 27187182 TI - A High Phosphorus Diet Affects Lipid Metabolism in Rat Liver: A DNA Microarray Analysis. AB - A high phosphorus (HP) diet causes disorders of renal function, bone metabolism, and vascular function. We previously demonstrated that DNA microarray analysis is an appropriate method to comprehensively evaluate the effects of a HP diet on kidney dysfunction such as calcification, fibrillization, and inflammation. We reported that type IIb sodium-dependent phosphate transporter is significantly up regulated in this context. In the present study, we performed DNA microarray analysis to investigate the effects of a HP diet on the liver, which plays a pivotal role in energy metabolism. DNA microarray analysis was performed with total RNA isolated from the livers of rats fed a control diet (containing 0.3% phosphorus) or a HP diet (containing 1.2% phosphorus). Gene Ontology analysis of differentially expressed genes (DEGs) revealed that the HP diet induced down regulation of genes involved in hepatic amino acid catabolism and lipogenesis, while genes related to fatty acid beta-oxidation process were up-regulated. Although genes related to fatty acid biosynthesis were down-regulated in HP diet fed rats, genes important for the elongation and desaturation reactions of omega 3 and -6 fatty acids were up-regulated. Concentrations of hepatic arachidonic acid and eicosapentaenoic acid were increased in HP diet-fed rats. These essential fatty acids activate peroxisome proliferator-activated receptor alpha (PPARalpha), a transcription factor for fatty acid beta-oxidation. Evaluation of the upstream regulators of DEGs using Ingenuity Pathway Analysis indicated that PPARalpha was activated in the livers of HP diet-fed rats. Furthermore, the serum concentration of fibroblast growth factor 21, a hormone secreted from the liver that promotes fatty acid utilization in adipose tissue as a PPARalpha target gene, was higher (p = 0.054) in HP diet-fed rats than in control diet-fed rats. These data suggest that a HP diet enhances energy expenditure through the utilization of free fatty acids released via lipolysis of white adipose tissue. PMID- 27187185 TI - Exploration of the Independent and Joint Influences of Social Norms and Drinking Motives on Korean College Students' Alcohol Consumption. AB - Understanding what types of social norms are more or less influential and how they operate with respect to other psychological variables can provide valuable insights into the design of effective social norm campaigns. To this end, this study explores the roles of two types of social norms (injunctive norms and descriptive norms) and two types of drinking motives (social motives and conformity motives) in collegiate drinking behavior in South Korea. A survey of Korean college students (N = 569) revealed significant positive effects of injunctive norms, descriptive norms, and social motives on students' drinking frequency and quantity. Conformity motives were positively related to the frequency of drinking but negatively related to the quantity of drinking. Furthermore, the results revealed significant effects of the interactions between descriptive norms and social motives (on both the frequency and quantity of alcohol consumption), such that the positive effect of descriptive norms was more pronounced among individuals with stronger social motives. A similar pattern was observed in the interaction between injunctive norms and conformity motives (on frequency). Theoretical and practical implications of the findings for social norm campaigns seeking to curb drinking among college students are discussed. PMID- 27187184 TI - Hyperoxia-mediated LC3B activation contributes to the impaired transdifferentiation of type II alveolar epithelial cells (AECIIs) to type I cells (AECIs). AB - Life-saving mechanical ventilation can also cause lung injury through the overproduction of reactive oxygen species (ROS), leading to bronchopulmonary dysplasia (BPD)-like symptoms in preterm infants. It is reported that the autophagic protein microtubule-associated protein-1 light chain (LC)-3B can confer protection against hyperoxia-induced DNA damage in lung alveolar epithelium. However, its role in the transdifferentiation of type II alveolar epithelial cells (AECIIs) to type I cells (AECIs) is unclear and requires further investigation. In this study, newborn Sprague-Dawley rats were exposed to 90% oxygen for up to 14 days to mimic BPD in human infants, with neonatal pups exposed to room air (21% oxygen) as controls. Primary rat AECIIs were cultured under hyperoxic conditions for up to 24 hours to further investigate the underlying mechanisms. This study found that hyperoxia promoted a significant and time-dependent increase of AECII marker surfactant protein (SP)-C in the lung. The increase of AECI marker T1alpha was repressed by hyperoxia during lung development. These results indicated an impaired AECII transdifferentiation. Pulmonary ROS concentration and expression of autophagic protein LC-3B were increased gradually in response to hyperoxia exposure. Furthermore, AECIIs produced more ROS when cultured under hyperoxic conditions in vitro. Both the LC3B expression and the conversion from LC3BI to LC3BII were enhanced in hyperoxic AECs. Interestingly, inhibition of LC3B either by ROS inhibitor N acetyl-l-cysteine (NAC) or adenovirus-mediated LC3B shRNA could partly restore AECII transdifferentiation under hyperoxia condition. In summary, the current study reveals a novel role of activated LC3B induced by hyperoxia in AECII transdifferentiation. PMID- 27187186 TI - A bioengineered drug-Eluting scaffold accelerated cutaneous wound healing In diabetic mice. AB - Hyperglycemia in diabetic patients can greatly hinder the wound healing process. In this study we investigated if the engagement of F4/80(+) murine macrophages could accelerate the cutaneous wound healing in streptozotocin induced diabetic mice. To facilitate the engagement of macrophages, we engineered a drug-eluting electrospun scaffold with a payload of monocyte chemoattractant protein-1 (MCP 1). MCP-1 could be readily released from the scaffold within 3 days. The electrospun scaffold showed no cytotoxic effects on human keratinocytes in vitro. Full-thickness excisional cutaneous wound was created in diabetic mice. The wound fully recovered within 10 days in mice treated with the drug-eluting scaffold. In contrast, the wound took 14 days to fully recover in control groups. The use of drug-eluting scaffold also improved the re-epithelialization. Furthermore, we observed a larger population of F4/80(+) macrophages in the wound bed of mice treated with drug-eluting scaffolds on day 3. This marked increase of macrophages in the wound bed could have contributed to the accelerated wound healing. Our study shed new light on an immuno-engineering solution for wound healing management in diabetic patients. PMID- 27187187 TI - Amphipathic silica nanoparticles induce cytotoxicity through oxidative stress mediated and p53 dependent apoptosis pathway in human liver cell line HL-7702 and rat liver cell line BRL-3A. AB - The aim of this study was to evaluate the potential cytotoxicity and the underlying mechanism of amphipathic silica nanoparticles (SiO2 NPs) exposure to human normal liver HL-7702 cells and rat normal liver BRL-3A cells. Prior to the cellular studies, transmission electron microscopy (TEM), dynamic light scattering (DLS), and X ray diffraction (XRD) were used to characterize SiO2 NPs, which proved the amorphous nature of SiO2 NPs with TEM diameter of 19.8+/-2.7nm. Further studies proved that exposure to SiO2 NPs dose-dependently induced cytotoxicity as revealed by cell counting kit (CCK-8) and lactate dehydrogenase (LDH) assays, with more severe cytotoxicity in HL-7702 cells than BRL-3A cells. Reactive oxygen species (ROS) and glutathione (GSH) assays showed elevated oxidative stress in both cells. Morphological studies by microscopic observation, Hochest 33258 and AO/EB staining indicated significant apoptotic changes after the cells being exposed to SiO2 NPs. Further studies by western blot indicated that SiO2 NPs exposure to both cells up-regulated p53, Bax and cleaved caspase-3 expression and down-regulated Bcl-2 and caspase-3 levels. Activated caspase-3 activity detected by colorimetric assay kit and caspase-3/7 activity detected by fluorescent real-time detection kit were significantly increased by SiO2 NPs exposure. In addition, antioxidant vitamin C significantly attenuated SiO2 NPs induced caspase-3 activation, which indicated that SiO2 NPs-induced oxidative stress was involved in the process of HL-7702 and BRL-3A cell apoptosis. Taken together, these results suggested that SiO2 NPs-induced cytotoxicity in HL-7702 and BRL-3A cells was through oxidative stress mediated and p53, caspase-3 and Bax/Bcl-2 dependent pathway and HL-7702 cells were more sensitive to SiO2 NPs induced cytotoxicity than BRL-3A cells. PMID- 27187188 TI - PEGylated PLGA nanospheres optimized by design of experiments for ocular administration of dexibuprofen-in vitro, ex vivo and in vivo characterization. AB - Dexibuprofen-loaded PEGylated PLGA nanospheres have been developed to improve the biopharmaceutical profile of the anti-inflammatory drug for ocular administration. Dexibuprofen is the active enantiomer of ibuprofen and therefore lower doses may be applied to achieve the same therapeutic level. According to this, two batches of nanospheres of different drug concentrations, 0.5 and 1.0mg/ml respectively, have been developed (the latter corresponding to the therapeutic ibuprofen concentration for inflammatory eye diseases). Both batches were composed of negatively charged nanospheres (--14.1 and --15.9mV), with a mean particle size below 200nm, and a high encapsulation efficiency (99%). X-ray, FTIR, and DSC analyses confirmed that the drug was dispersed inside the matrix of the nanospheres. While the in vitro release profile was sustained up to 12h, the ex vivo corneal and scleral permeation profile demonstrated higher drug retention and permeation in the corneal tissue rather than in the sclera. These results were also confirmed by the quantification of dexibuprofen in ocular tissues after the in vivo administration of drug-loaded nanospheres. Cell viability studies confirmed that PEGylated-PLGA nanospheres were less cytotoxic than free dexibuprofen in the majority of the tested concentrations. Ocular in vitro (HET CAM test) and in vivo (Draize test) tolerance assays demonstrated the non irritant character of both nanosphere batches. In vivo anti-inflammatory effects were evaluated in albino rabbits before and after inflammation induction. Both batches confirmed to be effective to treat and prevent ocular inflammation. PMID- 27187189 TI - Crossing the blood-brain-barrier with transferrin conjugated carbon dots: A zebrafish model study. AB - Drug delivery to the central nervous system (CNS) in biological systems remains a major medical challenge due to the tight junctions between endothelial cells known as the blood-brain-barrier (BBB). Here we use a zebrafish model to explore the possibility of using transferrin-conjugated carbon dots (C-Dots) to ferry compounds across the BBB. C-Dots have previously been reported to inhibit protein fibrillation, and they are also used to deliver drugs for disease treatment. In terms of the potential medical application of C-Dots for the treatment of CNS diseases, one of the most formidable challenges is how to deliver them inside the CNS. To achieve this in this study, human transferrin was covalently conjugated to C-Dots. The conjugates were then injected into the vasculature of zebrafish to examine the possibility of crossing the BBB in vivo via transferrin receptor mediated endocytosis. The experimental observations suggest that the transferrin C-Dots can enter the CNS while C-Dots alone cannot. PMID- 27187190 TI - Synthesis of amino-rich silica-coated magnetic nanoparticles for the efficient capture of DNA for PCR. AB - Magnetic separation has great advantages over traditional bio-separation methods and has become popular in the development of methods for the detection of bacterial pathogens, viruses, and transgenic crops. Functionalization of magnetic nanoparticles is a key factor for efficient capture of the target analytes. In this paper, we report the synthesis of amino-rich silica-coated magnetic nanoparticles using a one-pot method. This type of magnetic nanoparticle has a rough surface and a higher density of amino groups than the nanoparticles prepared by a post-modification method. Furthermore, the results of hydrochloric acid treatment indicated that the magnetic nanoparticles were stably coated. The developed amino-rich silica-coated magnetic nanoparticles were used to directly adsorb DNA. After magnetic separation and blocking, the magnetic nanoparticles and DNA complexes were used directly for the polymerase chain reaction (PCR), without onerous and time-consuming purification and elution steps. The results of real-time quantitative PCR showed that the nanoparticles with higher amino group density resulted in improved DNA capture efficiency. The results suggest that amino-rich silica-coated magnetic nanoparticles are of great potential for efficient bio-separation of DNA prior to detection by PCR. PMID- 27187191 TI - Development and characterization of a pseudo multiple reaction monitoring method for the quantification of human uromodulin in urine. AB - BACKGROUND: Uromodulin is the most abundant protein in healthy human urine. Recently it has been suggested as a specific biomarker of renal tubular damage. We have developed a novel pseudo multiple reaction monitoring (pseudo MRM) for the protein's quantification in human urine. RESULTS: Selection of two peptides allowed quantification of uromodulin in human urine. The pseudo MRM quantified uromodulin in healthy individuals between 21 and 1344 nM and in autosomal dominant tubulointerstitial kidney disease-UMOD patients between 2 and 25 nM. CONCLUSION: The pseudo MRM allows greater confidence in assay specificity than traditional MRM methods and quantified uromodulin at concentrations higher than achievable by ELISA. Differences in urinary uromodulin concentration related to the rs4293393 promoter variant in the UMOD gene was confirmed. This method will be used to further investigate uromodulin as a biomarker of renal injury. PMID- 27187192 TI - Seasonal Succession of Fungi Associated with Ips typographus Beetles and Their Phoretic Mites in an Outbreak Region of Finland. AB - The ophiostomatoid fungi (Microascales and Ophiostomatales, Ascomycota) are common associates of Ips typographus, and include tree pathogens and species responsible for blue-stain of timber. Fungal assemblages associated with I. typographus have varied considerably between studies but few investigations have attempted to explain this variation. For this reason, we assessed the overall cultivable fungal diversity associated with I. typographus in a storm-felled spruce forest in south-eastern Finland. Fungi were isolated from the individually collected beetles as well as their phoretic mites in spring, summer and autumn, including different life stages of the beetle (hibernation, dispersal flight and first generation). The internal transcribed spacer (ITS) gene region was used to identify the fungi. A total of 32 operational taxonomic units (OTUs) were found and these resided in four fungal phyla/subphyla (24 Ascomycota, 2 Basidiomycota, 5 Mucoromycotina, 1 Mortierellomycotina) in association with adult bark beetles. Ophiostomatoid species were the most commonly detected fungal associates. A generalized linear model analysis showed a clear association between fungal communities and season, indicating seasonal succession among I. typographus associated fungi. The season of sampling appears to be an important factor that has resulted in inconsistencies between results in previous studies. Many of these fungi were also found on phoretic mites and their presence or absence could have influenced variation in patterns of association. PMID- 27187193 TI - CD59: A long-known complement inhibitor has advanced to a blood group system. AB - The blood group system number 35 is based on CD59, a 20-kDa membrane glycoprotein present on a large number of different cells, including erythrocytes. The major function of CD59 is to protect cells from complement attack. CD59 binds to complement components CS and C9 and prevents the polymerization of C9, which is required for the formation of the membrane attack complex (MAC). Other functions of CD59 in cellular immunity are less well defined. CD59 is inserted into the membrane by a glycosylphosphatidylinositol (GPI) anchor. A defect of this anchor causes lack of this protein from the cell membrane, which leads to an enhanced sensitivity towards complement attack. Patients with paroxysmal nocturnal hemoglobinuria (PNH) harbor a varying percentage of red blood cell clones with a defect in GPI-anchored proteins, including CD59. The most characteristic symptoms of this disease are episodes of hemolysis and thromboses. Although CD59 has been classified as a membrane protein for more than 25 years, an alloantibody directed against CD59 was found only recently. So far, the first and sole alloantibody described was detected in a CD59-deficient child. In 2014, CD59 received the status of a blood group system by the International Society for Blood Transfusion Red Cell Immunogenetics and Blood Group Terminology Working Party. Among a variety of almost 20 synonyms, the designation CD59 was chosen for the blood group system and CD59.l for the wild-type protein. The only three alleles published to date are null alleles. All CD59-deficient individuals recognized so far were severely ill, two of whom have died. Most of the reported cases present with a typical clinical picture within the first year of life that includes neuropathy, strokes, and mild Coombs-negative hemolysis. In one published case, the application of the complement inhibitor eculizumab caused a pronounced improvement of the clinical situation. PMID- 27187194 TI - Recovery of autologous reticulocytes by microhematocrit cell separation. AB - Reticulocytes can be separated from more mature red blood cells based on differences in density. A method for obtaining autologous reticulocytes in ethylenediaminetetraacetic acid (EDTA) whole blood samples containing both autologous and transfused cells uses a microhematocrit centrifuge. The less dense reticulocytes harvested from the top 5 mm of microhematocrit tubes can be used to determine the patient's phenotype or assess whether a transfusion reaction is taking place. This method can be performed using equipment, reagents, and supplies readily available in most laboratories. PMID- 27187195 TI - Transfusion-related acute lung injury in an era of TRALI risk mitigation. AB - Transfusion-related acute lung injury (TRALI) is a rare complication of transfusion, for which the true incidence remains obscure, since there are a number of factors that may lead to misdiagnosis. Despite this, it continues to be the leading cause of transfusion-associated mortality. Here we present a historical case of TRALI in an elderly female who received group AB plasma and discuss how current mitigation strategies would likely have prevented its occurrence. It is important to remember that both immune and non-immune factors play a role in TRALI pathogenesis, and although current preventative strategies may decrease TRALI's incidence, they likely will not eliminate it. PMID- 27187196 TI - Weak D type 67 in four related Canadian blood donors. AB - Correct donor D typing is critical to prevent recipient alloimmunization. No method can detect all variants, and the immunogenicity of many variants is unknown. Routine ABO and D serologic typings are performed in our laboratory by automated microplate testing. Until 2011, routine confirmation of D- status of first-time donors was performed by the manual tube indirect antiglobulin test (IAT); this was replaced by automated solid-phase testing including weak D testing by IAT. Selected donors are investigated by other methods. We describe four weak D type 67 (RHD*01W.67) donors whose samples tested as D- by automated microplate and manual methods but were later determined to be D+ by automated solid-phase and RHD gene analysis. Solid-phase serologic and molecular typing results of all four donors were identical. It was identified that the donors are of English-Irish descent; two are brothers and the others are cousins. Transfusion of blood from one of these donors likely resulted in alloimmunization to D in one of three recipients tested since no other documented exposures were identified. Lookback studies determined that two other D- recipients were not alloimmunized. PMID- 27187197 TI - Suspected acute hemolytic transfusion reaction mediated by anti-Di(a). AB - Anti-Di(a) can mediate hemolytic disease of the fetus and newborn, but it is unclear if it can cause hemolytic transfusion reactions (HTRs). To date, there has only been one report of a possible immediate HTR attributed to anti-Di(a). Our case report details an immediate HTR due to anti-Di(a) in a patient with pre existing liver failure. This reaction triggered multi-organ failure, and the patient subsequently died. This case also highlights the importance of considering HTRs even when routine antibody screening has been unremarkable, particularly when electronic crossmatch is used, because of the potential for an alloantibody against a low-prevalence antigen. PMID- 27187198 TI - Red cell antigen prevalence predicted by molecular testing in ethnic groups of South Texas blood donors. AB - Alloimmunization to red blood cell antigens is seen in patients receiving chronic blood transfusion. Knowing the prevalence of blood group antigens of the different ethnicities of South Texas donors can provide better management of rare blood inventory for patients in this geographical area. A total of 4369 blood donors were tested and analyzed for various antigens in the following blood group systems: ABO, Rh, Kell, Duffy, Kidd, MNS, Lutheran, Dombrock, Landsteiner-Wiener, Diego, Colton, and Scianna. Donors tested to be group 0 or A were serologically tested for the Rh (C, E, c, e) antigens. Those that tested as presumably R1R1, R2R2, or Ror were then genotyped. Donors constituted three major ethnicities: black (18.3%), Hispanic (36.3%), and Caucasian (41.1%); ethnicities comprised of Asian, American Indian, multiracial, and other accounted for the remaining donors (4.3%). The most likely common Rh phenotype for each ethnicity is as follows: black -Ror (44.4%), Hispanic -R1R1 (59.0%), and Caucasian -R1R1 (38.9%). The prevalence of Kell, Duffy, and Kidd blood group system antigens in black and Caucasian donors is comparable with published reports for the entire U.S. The black South Texas donor population had an 8.8 percent increase in prevalence of the Fy(a+b-) phenotype as compared with these published reports; the Hispanic South Texas donor population had a prevalence of 36.1 percent of the Fy(a+b-) phenotype. Regarding the Diego blood group system, the Hispanic donor population in South Texas had a prevalence of 93.5 percent for the Di(a-b+) phenotype as compared with published reports for the entire U.S. (>99.9%). The Hispanic population had a prevalence of 7.9 percent of donors testing as M-N+S-s+ as compared with 20.2 percent and 15.6 percent for black and Caucasian donors, respectively. This study helped us determine the prevalence of each of the blood group antigens in the South Texas donor population to establish and maintain adequate rare inventory of each. Molecular red blood cell genotyping allows transfusion services to increase their availability of rare phenotypes for chronically transfused patients. PMID- 27187199 TI - Pioneering surgery for retinal detachment in Australasia: a review. AB - In the 1930s there was excitement worldwide with the realization that Jules Gonin's observation that closing the retinal break was the key to successful retinal re-attachment surgery. Australians and New Zealanders kept pace with these developments despite the limitations of travel and communication in the 1930s. Dr J. Bruce Hamilton of Tasmania was training at Moorfields Eye Hospital in 1930 and was exposed to the surgical technique espoused by Gonin in its first year of being adopted in Britain. Walter Lockhart Gibson was the first in Australasia to report a successful retinal re-attachment operation in 1931. In the 1960s Australians made two significant contributions to retinal surgery: the Schultz-Crock portable indirect ophthalmoscope and the first instrument for closed pars plana vitrectomy. The latter was developed at the Royal Victorian Eye and Ear Hospital by Dr Jean-Marie Parel and Professor Gerard Crock, in association with Dr Robert Machemer, and it was used by Machemer when he carried out the world's first closed pars plana vitrectomy in 1971. PMID- 27187201 TI - Top-down analysis of protein samples by de novo sequencing techniques. AB - MOTIVATION: Recent technological advances have made high-resolution mass spectrometers affordable to many laboratories, thus boosting rapid development of top-down mass spectrometry, and implying a need in efficient methods for analyzing this kind of data. RESULTS: We describe a method for analysis of protein samples from top-down tandem mass spectrometry data, which capitalizes on de novo sequencing of fragments of the proteins present in the sample. Our algorithm takes as input a set of de novo amino acid strings derived from the given mass spectra using the recently proposed Twister approach, and combines them into aggregated strings endowed with offsets. The former typically constitute accurate sequence fragments of sufficiently well-represented proteins from the sample being analyzed, while the latter indicate their location in the protein sequence, and also bear information on post-translational modifications and fragmentation patterns. AVAILABILITY AND IMPLEMENTATION: Freely available on the web at http://bioinf.spbau.ru/en/twister CONTACT: vyatkina@spbau.ru or ppevzner@ucsd.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 27187202 TI - Calculating and scoring high quality multiple flexible protein structure alignments. AB - MOTIVATION: Calculating multiple protein structure alignments (MSAs) is important for understanding functional and evolutionary relationships between protein families, and for modeling protein structures by homology. While incorporating backbone flexibility promises to circumvent many of the limitations of rigid MSA algorithms, very few flexible MSA algorithms exist today. This article describes several novel improvements to the Kpax algorithm which allow high quality flexible MSAs to be calculated. This article also introduces a new Gaussian-based MSA quality measure called 'M-score', which circumvents the pitfalls of RMSD based quality measures. RESULTS: As well as calculating flexible MSAs, the new version of Kpax can also score MSAs from other aligners and from previously aligned reference datasets. Results are presented for a large-scale evaluation of the Homstrad, SABmark and SISY benchmark sets using Kpax and Matt as examples of state-of-the-art flexible aligners and 3DCOMB as an example of a state-of-the-art rigid aligner. These results demonstrate the utility of the M-score as a measure of MSA quality and show that high quality MSAs may be achieved when structural flexibility is properly taken into account. AVAILABILITY AND IMPLEMENTATION: Kpax 5.0 may be downloaded for academic use at http://kpax.loria.fr/ CONTACT: dave.ritchie@inria.fr SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 27187200 TI - A two-part mixed-effects model for analyzing longitudinal microbiome compositional data. AB - MOTIVATION: The human microbial communities are associated with many human diseases such as obesity, diabetes and inflammatory bowel disease. High throughput sequencing technology has been widely used to quantify the microbial composition in order to understand its impacts on human health. Longitudinal measurements of microbial communities are commonly obtained in many microbiome studies. A key question in such microbiome studies is to identify the microbes that are associated with clinical outcomes or environmental factors. However, microbiome compositional data are highly skewed, bounded in [0,1), and often sparse with many zeros. In addition, the observations from repeated measures in longitudinal studies are correlated. A method that takes into account these features is needed for association analysis in longitudinal microbiome data. RESULTS: In this paper, we propose a two-part zero-inflated Beta regression model with random effects (ZIBR) for testing the association between microbial abundance and clinical covariates for longitudinal microbiome data. The model includes a logistic regression component to model presence/absence of a microbe in the samples and a Beta regression component to model non-zero microbial abundance, where each component includes a random effect to account for the correlations among the repeated measurements on the same subject. Both simulation studies and the application to real microbiome data have shown that ZIBR model outperformed the previously used methods. The method provides a useful tool for identifying the relevant taxa based on longitudinal or repeated measures in microbiome research. AVAILABILITY AND IMPLEMENTATION: https://github.com/chvlyl/ZIBR CONTACT: hongzhe@upenn.edu. PMID- 27187203 TI - A simple yet accurate correction for winner's curse can predict signals discovered in much larger genome scans. AB - MOTIVATION: For genetic studies, statistically significant variants explain far less trait variance than 'sub-threshold' association signals. To dimension follow up studies, researchers need to accurately estimate 'true' effect sizes at each SNP, e.g. the true mean of odds ratios (ORs)/regression coefficients (RRs) or Z score noncentralities. Naive estimates of effect sizes incur winner's curse biases, which are reduced only by laborious winner's curse adjustments (WCAs). Given that Z-scores estimates can be theoretically translated on other scales, we propose a simple method to compute WCA for Z-scores, i.e. their true means/noncentralities. RESULTS: WCA of Z-scores shrinks these towards zero while, on P-value scale, multiple testing adjustment (MTA) shrinks P-values toward one, which corresponds to the zero Z-score value. Thus, WCA on Z-scores scale is a proxy for MTA on P-value scale. Therefore, to estimate Z-score noncentralities for all SNPs in genome scans, we propose F: DR I: nverse Q: uantile T: ransformation (FIQT). It (i) performs the simpler MTA of P-values using FDR and (ii) obtains noncentralities by back-transforming MTA P-values on Z-score scale. When compared to competitors, realistic simulations suggest that FIQT is more (i) accurate and (ii) computationally efficient by orders of magnitude. Practical application of FIQT to Psychiatric Genetic Consortium schizophrenia cohort predicts a non-trivial fraction of sub-threshold signals which become significant in much larger supersamples. CONCLUSIONS: FIQT is a simple, yet accurate, WCA method for Z-scores (and ORs/RRs, via simple transformations). AVAILABILITY AND IMPLEMENTATION: A 10 lines R function implementation is available at https://github.com/bacanusa/FIQT CONTACT: sabacanu@vcu.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 27187204 TI - seqlm: an MDL based method for identifying differentially methylated regions in high density methylation array data. AB - MOTIVATION: One of the main goals of large scale methylation studies is to detect differentially methylated loci. One way is to approach this problem sitewise, i.e. to find differentially methylated positions (DMPs). However, it has been shown that methylation is regulated in longer genomic regions. So it is more desirable to identify differentially methylated regions (DMRs) instead of DMPs. The new high coverage arrays, like Illuminas 450k platform, make it possible at a reasonable cost. Few tools exist for DMR identification from this type of data, but there is no standard approach. RESULTS: We propose a novel method for DMR identification that detects the region boundaries according to the minimum description length (MDL) principle, essentially solving the problem of model selection. The significance of the regions is established using linear mixed models. Using both simulated and large publicly available methylation datasets, we compare seqlm performance to alternative approaches. We demonstrate that it is both more sensitive and specific than competing methods. This is achieved with minimal parameter tuning and, surprisingly, quickest running time of all the tried methods. Finally, we show that the regional differential methylation patterns identified on sparse array data are confirmed by higher resolution sequencing approaches. AVAILABILITY AND IMPLEMENTATION: The methods have been implemented in R package seqlm that is available through Github: https://github.com/raivokolde/seqlm CONTACT: rkolde@gmail.com SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 27187205 TI - PRESS: PRotEin S-Sulfenylation server. AB - MOTIVATION: Transient S-sulfenylation of cysteine thiols mediated by reactive oxygen species plays a critical role in pathology, physiology and cell signaling. Therefore, discovery of new S-sulfenylated sites in proteins is of great importance towards understanding how protein function is regulated upon redox conditions. RESULTS: We developed PRESS (PRotEin S-Sulfenylation) web server, a server which can effectively predict the cysteine thiols of a protein that could undergo S-sulfenylation under redox conditions. We envisage that this server will boost and facilitate the discovery of new and currently unknown functions of proteins triggered upon redox conditions, signal regulation and transduction, thus uncovering the role of S-sulfenylation in human health and disease. AVAILABILITY AND IMPLEMENTATION: The PRESS web server is freely available at http://press-sulfenylation.cse.uoi.gr/ CONTACTS: agtzakos@gmail.com or gtzortzi@cs.uoi.gr SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 27187206 TI - SoFIA: a data integration framework for annotating high-throughput datasets. AB - MOTIVATION: Integrating heterogeneous datasets from several sources is a common bioinformatics task that often requires implementing a complex workflow intermixing database access, data filtering, format conversions, identifier mapping, among further diverse operations. Data integration is especially important when annotating next generation sequencing data, where a multitude of diverse tools and heterogeneous databases can be used to provide a large variety of annotation for genomic locations, such a single nucleotide variants or genes. Each tool and data source is potentially useful for a given project and often more than one are used in parallel for the same purpose. However, software that always produces all available data is difficult to maintain and quickly leads to an excess of data, creating an information overload rather than the desired goal oriented and integrated result. RESULTS: We present SoFIA, a framework for workflow-driven data integration with a focus on genomic annotation. SoFIA conceptualizes workflow templates as comprehensive workflows that cover as many data integration operations as possible in a given domain. However, these templates are not intended to be executed as a whole; instead, when given an integration task consisting of a set of input data and a set of desired output data, SoFIA derives a minimal workflow that completes the task. These workflows are typically fast and create exactly the information a user wants without requiring them to do any implementation work. Using a comprehensive genome annotation template, we highlight the flexibility, extensibility and power of the framework using real-life case studies. AVAILABILITY AND IMPLEMENTATION: https://github.com/childsish/sofia/releases/latest under the GNU General Public License CONTACT: liam.childs@hu-berlin.de SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 27187207 TI - Sequential Photo-oxidative [3 + 2] Cycloaddition/Oxidative Aromatization Reactions for the Synthesis of Pyrrolo[2,1-a]isoquinolines Using Molecular Oxygen as the Terminal Oxidant. AB - We report an efficient method for the synthesis of pyrrolo[2,1-a]isoquinoline derivatives using sequential [3 + 2] cycloaddition/oxidative aromatization reactions catalyzed by methylene blue with fluorescent light irradiation under an oxygen atmosphere. The products were obtained in moderate to good yields. PMID- 27187208 TI - A First-Principles Approach to the Dynamics and Electronic Properties of p Nitroaniline in Water. AB - Born-Oppenheimer molecular dynamics of p-nitroaniline (PNA) in water was carried out and the electronic structure was investigated by time-dependent density functional theory. Hydrogen bonding involving the PNA nitro and amine groups and the water molecules leads to an ~160 cm(-1) red shift of the nu(N-O) and nu(N-H) stretching frequencies relative to the gas phase species. Our estimate for the peak position of the charge transfer (CT) band in the absorption spectrum of PNA in water (~3.5 eV) is in good agreement with experimental data (3.3 eV). We have investigated the specific role played by local hydrogen bonding and electrostatic interactions on the electronic absorption spectrum. It is shown that although electrostatic interactions play a major role for explaining the structure of the PNA CT band in water, the theoretical prediction of the observed red shift is improved by the explicit consideration of local hydrogen bonding of PNA to water. For isolated PNA, we predict that the dipole moment of the second excited state (S2) is 9.6 D greater than ground state (S0) dipole, which is in good agreement with experimental information (8.2-9.3 D). Calculation of charge transfer indexes for the two first excitations of PNA in water indicates that despite the feature that a small fraction of S1 states (<5%) may exhibit some CT character, CT states in solution are mainly associated with S2 <- S0 transitions. PMID- 27187210 TI - Modifier cation effects on (29)Si nuclear shielding anisotropies in silicate glasses. AB - We have examined variations in the (29)Si nuclear shielding tensor parameters of SiO4 tetrahedra in a series of seven alkali and alkaline earth silicate glass compositions, Cs2O.4.81 SiO2, Rb2O.3.96 SiO2, Rb2O.2.25 SiO2, K2O.4.48 SiO2, Na2O.4.74 SiO2, BaO.2.64 SiO2, and SrO.2.36 SiO2, using natural abundance (29)Si two-dimensional magic-angle flipping (MAF) experiments. Our analyses of these 2D spectra reveal a linear dependence of the (29)Si nuclear shielding anisotropy of Q((3)) sites on the Si-non-bridging oxygen bond length, which in turn depends on the cation potential and coordination of modifier cations to the non-bridging oxygen. We also demonstrate how a combination of Cu(2+) as a paramagnetic dopant combined with echo train acquisition can reduce the total experiment time of (29)Si 2D NMR measurements by two orders of magnitude, enabling higher throughput 2D NMR studies of glass structure. PMID- 27187209 TI - Multicenter Survey of Current Practice Patterns in Perfusion MRI in Neuroradiology: Why, When, and How Is It Performed? AB - OBJECTIVE: Perfusion MRI is an advanced imaging technique with a number of potential neuroradiologic applications. However, there are few guidelines about the application of perfusion MRI in clinical practice. The purpose of this study was to assess when and how perfusion MRI is performed across national and international practices. MATERIALS AND METHODS: An international survey was conducted through the American Society of Neuroradiology e-mail list. The survey included questions relating to demographics, whether perfusion MRI was offered, technical details, reporting, and reimbursement. RESULTS: Most (81.0%) of the practices responding offered perfusion MRI; this proportion increases to 94.3% among academic and 95.3% among large practices. Intraaxial tumor, stroke, and arterial stenosis are the most frequent reasons for offering perfusion imaging. Most practices offer perfusion imaging on the basis of the judgment of the referring physician or person writing the protocol for the study, or they offer it for all intraaxial tumors. The most frequent method is dynamic susceptibility contrast-enhanced MRI (86.8%) followed by dynamic contrast-enhanced MRI (40.7%) and arterial spin-labeling MRI (34.8%). A minority (22.7%) of practices seek reimbursement for perfusion MRI. Most of the practices provide quantitative findings in radiology reports, most frequently cerebral blood volume (92.7%), cerebral blood (62.9%), and mean transit time (51.0%). CONCLUSION: Despite the paucity of high-quality trials and guidelines for specific clinical applications, perfusion MRI is widely used by both academic and private practices. A minority of practices attempt to obtain reimbursement. This widespread adoption of perfusion imaging beyond its apparent financial footprint suggests that practicing radiologists and referring clinicians find value in the technique and underscores the need for more high-quality trials to solidify understanding of the role of perfusion MRI. PMID- 27187211 TI - Revisiting spin-lattice relaxation time measurements for dilute spins in high resolution solid-state NMR spectroscopy. AB - Numerous nuclear magnetic resonance (NMR) measurements of spin-lattice relaxation times (T1S) for dilute spins such as (13)C have led to investigations of the motional dynamics of individual functional groups in solid materials. In this work, we revisit the Solomon equations and analyze how the heteronuclear cross relaxation between the dilute S (e.g. (13)C) and abundant I (e.g. (1)H) spins affects the measured T1S values in solid-state NMR in the absence of (1)H saturation during the recovery time. It is found theoretically that at the beginning of the S spin magnetization recovery, the existence of non-equilibrium I magnetization introduces the heteronuclear cross relaxation effect onto the recovery of the S spin magnetization and confirmed experimentally that such a heteronuclear cross relaxation effect results in the recovery overshoot phenomena for the dilute spins when T1S is on the same order of T1H, leading to inaccurate measurements of the T1S values. Even when T1S is ten times larger than T1H, the heteronuclear cross relaxation effect on the measured T1S values is still noticeable. Furthermore, this cross relaxation effect on recovery trajectory of the S spins can be manipulated and even suppressed by preparing the initial I and S magnetization, so as to obtain the accurate T1S values. A sample of natural abundance l-isoleucine powder has been used to demonstrate the T1S measurements and their corresponding measured T1C values under various experimental conditions. PMID- 27187212 TI - Shadowing the wandering mind: how understanding the mind-wandering state can inform our appreciation of conscious experience. AB - The mind-wandering state illustrates two fundamental aspects of consciousness: its generative nature, which is reflected by the stimulus-independent content of thought that occurs when our minds wander; and metacognition, the unique capacity of the mind to reflect and understand itself. Self-generated thought, which allows us to consider people and events that are not present in the immediate environment, and metacognition, allowing us to introspect and report our inner experiences, are both essential to the scientific study of mind-wandering. Nevertheless, they also inevitably lead to specific issues that mirror more general problems in the field of consciousness research. The generative nature of consciousness makes it difficult to have direct control on the phenomenon, and the act of introspecting on inner experience has the potential to influence the state itself. We illustrate how the field of mind-wandering research can overcome these problems. Its generative nature can be understood by triangulating the objective measures (such as neural function) with subjective measures of experience and it can be manipulated indirectly by varying the demands of the external environment. Furthermore, we describe candidate covert markers for the mind-wandering state, which allow the phenomenon to be observed without direct interference, minimizing the concern that instructions to introspect necessarily change conscious experience. WIREs Cogn Sci 2016, 7:233-246. doi: 10.1002/wcs.1392 For further resources related to this article, please visit the WIREs website. PMID- 27187215 TI - Culture, Courage, Competence. PMID- 27187216 TI - Supporting Our Patients in Understanding the Insurance Conundrum. PMID- 27187214 TI - Prediction of isometric motor tasks and effort levels based on high-density EMG in patients with incomplete spinal cord injury. AB - OBJECTIVE: The development of modern assistive and rehabilitation devices requires reliable and easy-to-use methods to extract neural information for control of devices. Group-specific pattern recognition identifiers are influenced by inter-subject variability. Based on high-density EMG (HD-EMG) maps, our research group has already shown that inter-subject muscle activation patterns exist in a population of healthy subjects. The aim of this paper is to analyze muscle activation patterns associated with four tasks (flexion/extension of the elbow, and supination/pronation of the forearm) at three different effort levels in a group of patients with incomplete Spinal Cord Injury (iSCI). APPROACH: Muscle activation patterns were evaluated by the automatic identification of these four isometric tasks along with the identification of levels of voluntary contractions. Two types of classifiers were considered in the identification: linear discriminant analysis and support vector machine. MAIN RESULTS: Results show that performance of classification increases when combining features extracted from intensity and spatial information of HD-EMG maps (accuracy = 97.5%). Moreover, when compared to a population with injuries at different levels, a lower variability between activation maps was obtained within a group of patients with similar injury suggesting stronger task-specific and effort level-specific co-activation patterns, which enable better prediction results. SIGNIFICANCE: Despite the challenge of identifying both the four tasks and the three effort levels in patients with iSCI, promising results were obtained which support the use of HD-EMG features for providing useful information regarding motion and force intention. PMID- 27187217 TI - The Role of Shared Decision Making in Patient-Centered Care and Orthopaedics. AB - Shared decision making (SDM) is gaining momentum within the delivery of patient centered care. Shared decision making takes into account the findings from current evidence-based practice, in addition to the patient's values, desires, and preferences. This article reviews the phases of SDM: patient engagement, discussion, and decision, in addition to the role SDM plays in the specialty of orthopaedics. PMID- 27187213 TI - Giraffe genome sequence reveals clues to its unique morphology and physiology. AB - The origins of giraffe's imposing stature and associated cardiovascular adaptations are unknown. Okapi, which lacks these unique features, is giraffe's closest relative and provides a useful comparison, to identify genetic variation underlying giraffe's long neck and cardiovascular system. The genomes of giraffe and okapi were sequenced, and through comparative analyses genes and pathways were identified that exhibit unique genetic changes and likely contribute to giraffe's unique features. Some of these genes are in the HOX, NOTCH and FGF signalling pathways, which regulate both skeletal and cardiovascular development, suggesting that giraffe's stature and cardiovascular adaptations evolved in parallel through changes in a small number of genes. Mitochondrial metabolism and volatile fatty acids transport genes are also evolutionarily diverged in giraffe and may be related to its unusual diet that includes toxic plants. Unexpectedly, substantial evolutionary changes have occurred in giraffe and okapi in double strand break repair and centrosome functions. PMID- 27187218 TI - The Role of Shared Decision Making in Patient-Centered Care and Orthopaedics. PMID- 27187220 TI - Management of Acute Lumbar Injuries in the Workplace. PMID- 27187219 TI - Management of Acute Lumbar Injuries in the Workplace. AB - Occupational acute lumbar injuries are a common injury. One intervention that is unique to occupational health is the determination of the amount of physical activity that an injured worker can perform without increasing the risk of further injury. Clinical recommendations suggest that workers continue to stay active; however, it is still the clinician's responsibility to determine the level of activity. The level of work activity is determined on a case-to-case basis and is done by evaluating the physical capacity of an injured worker and the job description. Current evidence-based guidelines suggest that staying active may actually reduce pain levels. The purpose of this evidence-based literature review is to outline the proper assessment and management of workers who have sustained a work-related low back injury. The related literature has been reviewed as well as red flags for more severe neurological conditions that require more in-depth evaluation. Determining the safe level of activity and guided return to work have been discussed. PMID- 27187221 TI - Establishment and Evaluation of an Anterior Cruciate Ligament Injury Prevention Program. AB - BACKGROUND: In female high school athletes, soccer continues to be a high-risk sport for sustaining an anterior cruciate ligament injury. Literature reviews indicate the best injury prevention programs (IPPs) focus on increasing core strength and proprioception in this age group. PURPOSE: An IPP was created for a small Midwestern high school girls' soccer team. The goal of the study was to evaluate the effectiveness of the IPP on core strength and proprioception. METHODS: The IPP incorporated functional movement applied science and exercises. Students were tested pre- and postseason. Results were analyzed using paired samples t tests. RESULTS: Statistically significant results in improved core measures were noted. CONCLUSION: This IPP, which utilized functional movement and training, could be utilized by other teams for increasing core strength and proprioception of players, as well as adding to the body of literature utilizing functional movement. PMID- 27187222 TI - Establishment and Evaluation of an Anterior Cruciate Ligament Injury Prevention Program. PMID- 27187223 TI - Information and Control Preferences and Their Relationship With the Knowledge Received Among European Joint Arthroplasty Patients. AB - BACKGROUND: The prevalence of joint arthroplasties is increasing internationally, putting increased emphasis on patient education. PURPOSE: This study describes information and control preferences of patients with joint arthroplasty in seven European countries, and explores their relationships with patients' received knowledge. METHODS: The data (n = 1,446) were collected during 2009-2012 with the Krantz Health Opinion Survey and the Received Knowledge of Hospital Patient scale. RESULTS: European patients with joint arthroplasty had low preferences. Older patients had less information preferences than younger patients (p = .0001). In control preferences there were significant relationships with age (p = .021), employment in healthcare/social services (p = .033), chronic illness (p = .002), and country (p = .0001). Received knowledge of the patients did not have any relationships with information preferences. Instead, higher control preferences were associated with less received knowledge. CONCLUSION: The relationship between European joint arthroplasty patients' preferences and the knowledge they have received requires further research. PMID- 27187224 TI - Blood Transfusion Practices in Patients Undergoing Total Joint Replacement: A Research Study. AB - BACKGROUND: Many studies show it is not necessary to transfuse according to a single hemoglobin level, but rather it is necessary to assess the combination of signs, symptoms, and laboratory measures. PURPOSE: The purpose of this study was to evaluate the use of red blood cell (RBC) transfusions in patients who underwent total hip or knee replacement. METHODS: The study comprised 2 retrospective medical record reviews: Phase 1 included data prior to the RBC transfusion order set and elimination of autologous blood. Phase 2 included postimplementation data. RESULTS: There were a decreased number of patients receiving blood transfusions after implementing the RBC transfusion order set and a decreased hemoglobin trigger value. The strongest predictor of receiving a blood transfusion was autologous blood donation. CONCLUSION: Use of the order set will decrease unnecessary transfusions hospital-wide. PMID- 27187225 TI - Enhanced Rehabilitation and Care Models for Adults With Dementia Following Hip Fracture Surgery. PMID- 27187226 TI - Greater Tuberosity Fracture of the Humerus: A Case Report. PMID- 27187227 TI - Greater Tuberosity Fracture of the Humerus: A Case Report. PMID- 27187230 TI - Disentangling the initiation from the response in joint attention: an eye tracking study in toddlers with autism spectrum disorders. AB - Joint attention (JA), whose deficit is an early risk marker for autism spectrum disorder (ASD), has two dimensions: (1) responding to JA and (2) initiating JA. Eye-tracking technology has largely been used to investigate responding JA, but rarely to study initiating JA especially in young children with ASD. The aim of this study was to describe the differences in the visual patterns of toddlers with ASD and those with typical development (TD) during both responding JA and initiating JA tasks. Eye-tracking technology was used to monitor the gaze of 17 children with ASD and 15 age-matched children with TD during the presentation of short video sequences involving one responding JA and two initiating JA tasks (initiating JA-1 and initiating JA-2). Gaze accuracy, transitions and fixations were analyzed. No differences were found in the responding JA task between children with ASD and those with TD, whereas, in the initiating JA tasks, different patterns of fixation and transitions were shown between the groups. These results suggest that children with ASD and those with TD show different visual patterns when they are expected to initiate joint attention but not when they respond to joint attention. We hypothesized that differences in transitions and fixations are linked to ASD impairments in visual disengagement from face, in global scanning of the scene and in the ability to anticipate object's action. PMID- 27187231 TI - Glucagon-like peptide 1 receptor activation regulates cocaine actions and dopamine homeostasis in the lateral septum by decreasing arachidonic acid levels. AB - Agonism of the glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) has been effective at treating aspects of addictive behavior for a number of abused substances, including cocaine. However, the molecular mechanisms and brain circuits underlying the therapeutic effects of GLP-1R signaling on cocaine actions remain elusive. Recent evidence has revealed that endogenous signaling at the GLP-1R within the forebrain lateral septum (LS) acts to reduce cocaine induced locomotion and cocaine conditioned place preference, both considered dopamine (DA)-associated behaviors. DA terminals project from the ventral tegmental area to the LS and express the DA transporter (DAT). Cocaine acts by altering DA bioavailability by targeting the DAT. Therefore, GLP-1R signaling might exert effects on DAT to account for its regulation of cocaine-induced behaviors. We show that the GLP-1R is highly expressed within the LS. GLP-1, in LS slices, significantly enhances DAT surface expression and DAT function. Exenatide (Ex-4), a long-lasting synthetic analog of GLP-1 abolished cocaine induced elevation of DA. Interestingly, acute administration of Ex-4 reduces septal expression of the retrograde messenger 2-arachidonylglycerol (2-AG), as well as a product of its presynaptic degradation, arachidonic acid (AA). Notably, AA reduces septal DAT function pointing to AA as a novel regulator of central DA homeostasis. We further show that AA oxidation product gamma-ketoaldehyde (gamma KA) forms adducts with the DAT and reduces DAT plasma membrane expression and function. These results support a mechanism in which postsynaptic septal GLP-1R activation regulates 2-AG levels to alter presynaptic DA homeostasis and cocaine actions through AA. PMID- 27187232 TI - Anhedonia and general distress show dissociable ventromedial prefrontal cortex connectivity in major depressive disorder. AB - Anhedonia, the reduced ability to experience pleasure in response to otherwise rewarding stimuli, is a core symptom of major depressive disorder (MDD). Although the posterior ventromedial prefrontal cortex (pVMPFC) and its functional connections have been consistently implicated in MDD, their roles in anhedonia remain poorly understood. Furthermore, it is unknown whether anhedonia is primarily associated with intrinsic 'resting-state' pVMPFC functional connectivity or an inability to modulate connectivity in a context-specific manner. To address these gaps, a pVMPFC region of interest was first identified using activation likelihood estimation meta-analysis. pVMPFC connectivity was then examined in relation to anhedonia and general distress symptoms of depression, using both resting-state and task-based functional magnetic resonance imaging involving pleasant music, in current MDD and healthy control groups. In MDD, pVMPFC connectivity was negatively correlated with anhedonia but not general distress during music listening in key reward- and emotion-processing regions, including nucleus accumbens, ventral tegmental area/substantia nigra, orbitofrontal cortex and insula, as well as fronto-temporal regions involved in tracking complex sound sequences, including middle temporal gyrus and inferior frontal gyrus. No such dissociations were observed in the healthy controls, and resting-state pVMPFC connectivity did not dissociate anhedonia from general distress in either group. Our findings demonstrate that anhedonia in MDD is associated with context-specific deficits in pVMPFC connectivity with the mesolimbic reward system when encountering pleasurable stimuli, rather than a static deficit in intrinsic resting-state connectivity. Critically, identification of functional circuits associated with anhedonia better characterizes MDD heterogeneity and may help track of one of its core symptoms. PMID- 27187234 TI - The potential role of nitrous oxide in the etiology of autism spectrum disorder. PMID- 27187233 TI - Cognitive and oculomotor performance in subjects with low and high schizotypy: implications for translational drug development studies. AB - The development of drugs to improve cognition in patients with schizophrenia is a major unmet clinical need. A number of promising compounds failed in recent clinical trials, a pattern linked to poor translation between preclinical and clinical stages of drug development. Seeking proof of efficacy in early Phase 1 studies in surrogate patient populations (for example, high schizotypy individuals where subtle cognitive impairment is present) has been suggested as a strategy to reduce attrition in the later stages of drug development. However, there is little agreement regarding the pattern of distribution of schizotypal features in the general population, creating uncertainty regarding the optimal control group that should be included in prospective trials. We aimed to address this question by comparing the performance of groups derived from the general population with low, average and high schizotypy scores over a range of cognitive and oculomotor tasks. We found that tasks dependent on frontal inhibitory mechanisms (N-Back working memory and anti-saccade oculomotor tasks), as well as a smooth-pursuit oculomotor task were sensitive to differences in the schizotypy phenotype. In these tasks the cognitive performance of 'low schizotypes' was significantly different from 'high schizotypes' with 'average schizotypes' having an intermediate performance. These results indicate that for evaluating putative cognition enhancers for treating schizophrenia in early-drug development studies the maximum schizotypy effect would be achieved using a design that compares low and high schizotypes. PMID- 27187235 TI - The NADPH oxidase NOX2 as a novel biomarker for suicidality: evidence from human post mortem brain samples. AB - Recent evidence points towards a role of oxidative stress in suicidality. However, few studies were carried out on the sources of reactive oxygen species (ROS) in subjects with suicidal behaviour. We have previously demonstrated that the NADPH oxidase NOX2-derived oxidative stress has a major role in the development of neuropathological alterations observed in an animal model of psychosis. Here, we investigated the possible increase in NOX2 in post mortem brain samples of subjects who died by asphyctic suicide (AS) compared with controls (CTRL) and subjects who died by non-suicidal asphyxia (NSA). We found that NOX2 expression was significantly higher in the cortex of AS subjects than in the other two experimental groups. NOX2 immunostaining was mainly detected in GABAergic neurons, with a minor presence of NOX2-positive-stained cells in glutamatergic and dopaminergic neurons, as well as astrocytes and microglia. A sustained increase in the expression of 8-hydroxy-2'-deoxyguanosine, an indirect marker of oxidative stress, was also detected in the cortex of AS subjects, compared with CTRL and NSA subjects. A significant elevation in cortical interleukin-6 immunoreactivity in AS subjects suggested an involvement of cytokine-associated molecular pathways in NOX2 elevations. Our results suggest that the increase in NOX2-derived oxidative stress in the brain might be involved in the neuropathological pathways leading to suicidal behaviour. These results may open innovative insights in the identification of new pathogenetic and necroscopic biomarkers, predictive for suicidality and potentially useful for suicide prevention. PMID- 27187238 TI - Persistent State-of-Charge Heterogeneity in Relaxed, Partially Charged Li1- x Ni1/3 Co1/3 Mn1/3 O2 Secondary Particles. AB - Ex situ transmission X-ray microscopy reveals micrometer-scale state-of-charge heterogeneity in solid-solution Li1- x Ni1/3 Co1/3 Mn1/3 O2 secondary particles even after extensive relaxation. The heterogeneity generates overcharged domains at the cutoff voltage, which may accelerate capacity fading and increase impedance with extended cycling. It is proposed that optimized secondary structures can minimize the state-of-charge heterogeneity by mitigating the buildup of nonuniform internal stresses associated with volume changes during charge. PMID- 27187236 TI - Effects of acute aerobic exercise on neural correlates of attention and inhibition in adolescents with bipolar disorder. AB - Executive dysfunction is common during and between mood episodes in bipolar disorder (BD), causing social and functional impairment. This study investigated the effect of acute exercise on adolescents with BD and healthy control subjects (HC) to test for positive or negative consequences on neural response during an executive task. Fifty adolescents (mean age 16.54+/-1.47 years, 56% female, 30 with BD) completed an attention and response inhibition task before and after 20 min of recumbent cycling at ~70% of age-predicted maximum heart rate. 3 T functional magnetic resonance imaging data were analyzed in a whole brain voxel wise analysis and as regions of interest (ROI), examining Go and NoGo response events. In the whole brain analysis of Go trials, exercise had larger effect in BD vs HC throughout ventral prefrontal cortex, amygdala and hippocampus; the profile of these effects was of greater disengagement after exercise. Pre exercise ROI analysis confirmed this 'deficit in deactivation' for BDs in rostral ACC and found an activation deficit on NoGo errors in accumbens. Pre-exercise accumbens NoGo error activity correlated with depression symptoms and Go activity with mania symptoms; no correlations were present after exercise. Performance was matched to controls and results survived a series of covariate analyses. This study provides evidence that acute aerobic exercise transiently changes neural response during an executive task among adolescents with BD, and that pre exercise relationships between symptoms and neural response are absent after exercise. Acute aerobic exercise constitutes a biological probe that may provide insights regarding pathophysiology and treatment of BD. PMID- 27187246 TI - Insights into the Mechanism and Kinetics of Thermo-Oxidative Degradation of HFPE High Performance Polymer. AB - The growing requisite for materials having high thermo-oxidative stability makes the design and development of high performance materials an active area of research. Fluorination of the polymer backbone is a widely applied strategy to improve various properties of the polymer, most importantly the thermo-oxidative stability. Many of these fluorinated polymers are known to have thermo-oxidative stability up to 700 K. However, for space and aerospace applications, it is important to improve its thermo-oxidative stability beyond 700 K. Molecular-level details of the thermo-oxidative degradation of such polymers can provide vital information to improve the polymer. In this spirit, we have applied quantum mechanical and microkinetic analysis to scrutinize the mechanism and kinetics of the thermo-oxidative degradation of a fluorinated polymer with phenylethenyl end cap, HFPE. This study gives an insight into the thermo-oxidative degradation of HFPE and explains most of the experimental observations on the thermo-oxidative degradation of this polymer. Thermolysis of C-CF3 bond in the dianhydride component (6FDA) of HFPE is found to be the rate-determining step of the degradation. Reaction pathways that are responsible for the experimentally observed weight loss of the polymer is also scrutinized. On the basis of these results, we propose a modification of HFPE polymer to improve its thermo oxidative stability. PMID- 27187245 TI - Accumulation of sugars in the xylem apoplast observed under water stress conditions is controlled by xylem pH. AB - Severe water stress constrains, or even stops, water transport in the xylem due to embolism formation. Previously, the xylem of poplar trees was shown to respond to embolism formation by accumulating carbohydrates in the xylem apoplast and dropping xylem sap pH. We hypothesize that these two processes may be functionally linked as lower pH activates acidic invertases degrading sucrose and inducing accumulation of monosaccharides in xylem apoplast. Using a novel in vivo method to measure xylem apoplast pH, we show that pH drops from ~6.2 to ~5.6 in stems of severely stressed plants and rises following recovery of stem water status. We also show that in a lower pH environment, sugars are continuously accumulating in the xylem apoplast. Apoplastic carbohydrate accumulation was reduced significantly in the presence of a proton pump blocker (orthovanadate). These observations suggest that a balance in sugar concentrations exists between the xylem apoplast and symplast that can be controlled by xylem pH and sugar concentration. We conclude that lower pH is related to loss of xylem transport function, eventually resulting in accumulation of sugars that primes stems for recovery from embolism when water stress is relieved. PMID- 27187247 TI - Perception of hand movement by mirror reflection evokes brain activation in the motor cortex contralateral to a non-moving hand. AB - We investigated whether perception of hand movement via mirror reflection evokes activation in the motor cortex (M1) contralateral to the non-moving hand (the M1 ipsilateral to the moving hand). Continuous electroencephalography (EEG) was recorded from 14 participants while they performed unimanual extension-flexion hand movements in direct view and mirror view conditions. We measured the lateralized readiness potential (LRP) as a marker of M1 activation in both conditions. Both the direct and mirror view conditions produced LRPs, with the mirror view conditions revealing clear activation in M1 contralateral to the non moving hand (ipsilateral to the moving hand) during both flexion and extension phases. This unambiguous demonstration of M1 activation in association with a non moving hand (which is visually-perceived as moving), suggests that perception of movement can directly lead to M1 activation. PMID- 27187248 TI - Evaluation of Sidestream Darkfield Microscopy for Real-Time Imaging Acellular Dermal Matrix Revascularization. AB - BACKGROUND: Acellular dermal matrices (ADMs) serve as a regenerative framework for host cell integration and collagen deposition to augment the soft tissue envelope in ADM-assisted breast reconstruction-a process dependent on vascular ingrowth. To date noninvasive intra-operative imaging techniques have been inadequate to evaluate the revascularization of ADM. METHODS: We investigated the safety, feasibility, and efficacy of sidestream darkfield (SDF) microscopy to assess the status of ADM microvascular architecture in 8 patients at the time of tissue expander to permanent implant exchange during 2-stage ADM-assisted breast reconstruction. The SDF microscopy is a handheld device, which can be used intraoperatively for the real-time assessment of ADM blood flow, vessel density, vessel size, and branching pattern. The SDF microscopy was used to assess the microvascular architecture in the center and border zone of the ADM and to compare the native, non-ADM-associated capsule in each patient as a within subject control. RESULTS: No incidences of periprosthetic infection, explantation, or adverse events were reported after SDF image acquisition. Native capsules demonstrate a complex, layered architecture with an average vessel area density of 14.9 mm/mm and total vessel length density of 12.3 mm/mm. In contrast to native periprosthetic capsules, ADM-associated capsules are not uniformly vascularized structures and demonstrate 2 zones of microvascular architecture. The ADM and native capsule border zone demonstrates palisading peripheral vascular arcades with continuous antegrade flow. The central zone of the ADM demonstrates punctate perforating vascular plexi with intermittent, sluggish flow, and intervening 2- to 3-cm watershed zones. CONCLUSIONS: Sidestream darkfield microscopy allows for real-time intraoperative assessment of ADM revascularization and serves as a potential methodology to compare revascularization parameters among commercially available ADMs. Thr SDF microscopy demonstrates that the periprosthetic capsule in ADM-assisted implant based breast reconstruction is not a uniformly vascularized structure. PMID- 27187249 TI - Abdominoplasty With Scarpa Fascia Preservation. AB - The plane of dissection used during a full abdominoplasty has been implicated on the seroma rate. Avoiding the classic plane of dissection on top of the rectus fascia and using a more superficial plane of dissection has been suggested as a strategy to improve recovery and lower the complication rate. The authors have been applying this principle in their practice for more than a decade, and they performed 2 prospective comparative studies to evaluate the clinical effects of using a more superficial plane of dissection (with Scarpa fascia preservation) during a full abdominoplasty.The technique is presented and explained along with the results of both comparative studies.The results of both studies are discussed particularly the effects on drain volume (total and daily), the duration of drain usage and the avoidance of "long drainers." These are very relevant advantages of the technique that have not been discussed in the literature. The results and surgical strategies used by other authors which apply a more superficial plane of dissection are presented.Controversy still exits on the manipulation of the deep fat compartment by liposuction or direct fat excision. No manipulation is another option which should be considered but it has been questioned due to the risk of aesthetic compromise. A morphometric study performed on the surgical specimens of 41 female patients submitted to a full abdominoplasty validates that option.Based on this evidence, the authors recommend that surgeons consider performing abdominoplasties using a more superficial plane of dissection in the infraumbilical area with total preservation of Scarpa fascia and the deep fat compartment. The classic plane of dissection, on top of the deep fascia, should be avoided in the lower abdomen. PMID- 27187237 TI - TLR4 signaling in VTA dopaminergic neurons regulates impulsivity through tyrosine hydroxylase modulation. AB - Alcohol dependence is a complex disorder that initiates with episodes of excessive alcohol drinking known as binge drinking, and has a 50-60% risk contribution from inherited susceptibility genes. Cognitive impulsivity is a heritable trait that may set the stage for transition to alcohol dependence but its role in the ethanol-seeking behavior and the involved genes are still poorly understood. We have previously shown that alcohol-preferring P rats have innately elevated levels of a neuronal Toll-like receptor 4 (TLR4) signal in the ventral tegmental area (VTA) that controls the initiation of excessive alcohol drinking. Here we report that TLR4 is localized in dopaminergic (TH+) neurons and it upregulates the expression of tyrosine hydroxylase (TH) through a cAMP-dependent protein kinase (PKA)/cyclic AMP response element binding protein (CREB) signal. P rats have higher impulsivity than wild-type (WT) rats and VTA infusion of a non replicating Herpes simplex virus (HSV) vector for TLR4-specific small interfering RNA (siRNA; pHSVsiTLR4) inhibits both impulsivity and TLR4/TH expression. A scrambled siRNA vector does not affect gene expression or impulsivity. The data suggest that TLR4 signaling in VTA dopaminergic neurons controls impulsivity related to the regulation of TH expression, likely contributing to the initiation of alcohol drinking and its transition to alcohol dependence. PMID- 27187250 TI - In Situ Venous Bypass for Chronic Hand Ischemia: A Review of 25 Cases in 23 Patients. AB - BACKGROUND: Chronic ischemia of the hand in the setting of atherosclerotic disease is a challenging problem that leads to serial amputations and significant morbidity. Salvage using an in situ venous bypass has been described. In selected cases, leaving the vein in situ for bypass allows a good size match for anastomosis at the wrist or palmar arch. Due to the rarity of the condition, there is a paucity of data regarding the efficacy of this technique. METHODS: Outcomes in 23 consecutive patients that underwent a total of 25 in situ vein grafts over a 16-year period were retrospectively reviewed. RESULTS: Eighteen were men and 5 were women with a mean age of 61 years. Target vessels at the wrist or palmar arch were identified on preoperative vascular imaging. The cephalic vein (n = 19, 76%) was most commonly used followed by the basilic vein (n = 6, 24%). Overall patency rate at a mean follow-up period of 12.1 months was 92%. Success as determined by both symptomatic improvement and resolution of the ischemic changes or toleration of revision amputation was achieved in 16 (64%) cases. Postoperative complications occurred in ten cases (40 %). Progression of ischemia occurred in 7 cases (28 %) and 3 (12 %) of these cases required a hand amputation. CONCLUSIONS: In situ vein grafts in the upper extremity offer good short-term patency rates and can be used for salvage of chronic hand ischemia. PMID- 27187251 TI - Vertical Mastectomy Incision in Implant Breast Reconstruction After Skin Sparing Mastectomy: Advantages and Outcomes. AB - BACKGROUND: The type of since skin-sparing mastectomy (SSM) incision directly impacts the final aesthetic and functional results of reconstruction. Different incisions are used for SSM depending on tumor location, previous biopsy scars, breast weight, and ptosis degree. A vertical scar is less visible to the patient, reminiscent of a mastopexy, and patients may not have the stigma of mastectomy. OBJECTIVE: This study investigates complication rates, patient demographics, patient reported outcomes, and plastic surgeon evaluations to compare vertical incision mastectomy to other incisions. METHODS: After institutional review board approval, a retrospective chart review was performed. A total population of 167 patients that underwent mastectomy with tissue expander reconstruction was separated into vertical incision and nonvertical incision mastectomy groups consisting of 38 and 129 patients, respectively. Patient demographics, complications, tumor margins, staging, breast weight, and breast implant volume were compared. BREASTQ Survey analysis was conducted using patient reported outcomes from the patient's perspective. Aesthetic evaluations of postoperative photos were systematically scored by plastic surgeons to obtain data from the plastic surgeon's perspective. RESULTS: Vertical incision orientation did not increase surgical complication rates or mastectomy skin necrosis (P = 0.142). Vertical incisions did not interfere with obtaining adequate tumor margins (P = 0.907). Vertical incisions did not have a significantly different breast weight or implant volume. There was no statistical difference for patient satisfaction or plastic surgeon aesthetic evaluation. CONCLUSIONS: The use of vertical incision does not increase complication rates; does not interfere with tumor margins; and can be applied to all age, BMI, breast weight, and breast implant volume groups. PMID- 27187252 TI - Comparison of Reconstructive Outcomes in Breast Cancer Patients With Preexisting Subpectoral Implants: Implant-Sparing Mastectomy With Delayed Implant Exchange Versus Immediate Tissue Expander Reconstruction. AB - BACKGROUND: Women who have undergone prior augmentation mammoplasty represent a unique subset of breast cancer patients with several options available for breast reconstruction. We performed a single institution review of surgical outcomes of breast reconstruction performed in patients with breast cancer with prior history of subpectoral breast augmentation. METHODS: Institutional review board-approved retrospective review was conducted among patients with previously mentioned criteria treated at our institution between 2000 and 2014. Reconstructions were grouped into 2 categories as follows: (1) removal of preexisting subpectoral implant during mastectomy with immediate tissue expander placement and (2) implant-sparing mastectomy followed by delayed exchange to a larger implant. We reviewed demographics, tumor features, and reconstruction outcomes of these groups. RESULTS: Fifty-three patients had preexisting subpectoral implants. Of the 63 breast reconstructions performed, 18 (28.6%) had immediate tissue expander placed and 45 (71.4%) had implant-sparing mastectomy followed by delayed implant exchange. The groups were comparable based on age, body mass index, cancer type, tumor grade, TNM stage at presentation, and hormonal receptor status. No significant difference was noted between tumor margins or subsequent recurrence, mastectomy specimen weight, removed implant volume, volume of implant placed during reconstruction, or time from mastectomy to final implant placement. Rates of complications were significantly higher in the tissue expander group compared to the implant-sparing mastectomy group 7 (38.9%) versus 4 (8.9%) (P = 0.005). CONCLUSIONS: Implant-sparing mastectomy with delayed implant exchange in patients with preexisting subpectoral implants is safe and has fewer complications compared to tissue expander placement. There was no difference noted in the final volume of implant placed, time interval for final implant placement, or tumor margins. PMID- 27187253 TI - Procedural Portfolio Planning in Plastic Surgery, Part 1: Strategic Changes in Clinical Practice to Increase Physician Revenue, Improve Operative Throughput, and Maintain Patient Satisfaction. AB - PURPOSE: Portfolio planning in health care represents the strategic prioritization of services that permits an organization to better achieve its goals of margin and mission. Because of recent volatility in the economy, declining reimbursement, and rising costs of providing care, such strategic planning has become increasingly important if physicians want to remain leaders in health care. This project assesses the financial impact of procedural portfolio planning on an academic plastic surgery practice from the physician's perspective. METHODS: We tracked the top 50 procedures, defined as total charges per CPT code, that were performed in our baseline year, for 6 providers in a stable plastic surgery practice. At the end of the first year, we implemented 3 types of strategic changes: growth of areas with high contribution margin (laser resurfacing of burn scars), curtailment of high-risk procedures with negative contribution margin (panniculectomy in smokers), and improved efficiency of mission-critical services with high resource consumption (free-flap breast reconstruction). During the 2-year study period, we had no turnover in faculty, did not pursue any formal marketing, did not change our surgical fees or billing system, provided care independent of payer mix, and maintained our commitment to indigent care. Outcome measures included procedural charges and revenue, collection rates, work relative value units, operating room times, idle times (room time less case time), receipts/minute in operating room, uncompensated charity care, and patient satisfaction (Press-Gainey scores). Before the study period, annual incremental growth in our practice was 1% to 2%, in terms of charges and receipts. RESULTS: After implementation of the portfolio planning project, the financial position of our division improved significantly, with patient satisfaction rates increasing from 85.5% to 94.1% and charity care remaining constant at US $400,000 per year. Encounters, work relative value units, charges, and receipts all increased by 16% to 27%, with receipts/minute increasing from US $5.60 per minute to US $7.28 per minute. Interestingly, but not surprisingly, highest margin cases did not correspond with highest volume or highest revenue cases; portfolio analysis helped us to align these parameters, without sacrificing patient satisfaction or commitment to indigent care. The highest receipt/minute procedure was laser ablation of vascular lesions (US $23.87), whereas one of the lowest receipt/minute cases was muscle free flap (US $3.07). CONCLUSIONS: Procedural portfolio analysis is a powerful tool that can guide strategy and positively impact the financial position and clinical value of the services provided by an academic plastic surgery practice. Identifying high margin procedures allows the surgeon to focus marketing efforts, target areas of future growth, and optimize the blend of margin and mission. PMID- 27187254 TI - Procedural Portfolio Planning in Plastic Surgery, Part 2: Collaboration Between Surgeons and Hospital Administrators to Develop a Funds Flow Model for Procedures Performed at an Academic Medical Center. AB - INTRODUCTION: Although plastic surgeons make important contributions to the clinical, educational, and research missions of academic medical centers (AMCs), determining the financial value of a plastic surgery service can be difficult, due to complex cost accounting systems. We analyzed the financial impact of plastic surgery on an AMC, by examining the contribution margins and operating income of surgical procedures. METHODS: We collaborated with hospital administrators to implement 3 types of strategic changes: (1) growth of areas with high contribution margin, (2) curtailment of high-risk procedures with negative contribution margin, (3) improved efficiency of mission-critical services with high resource consumption. Outcome measures included: facility charges, hospital collections, contribution margin, operating margin, and operating room times. We also studied the top 50 Current Procedural Terminology codes (total case number * charge/case), ranking procedures for profitability, as determined by operating margin. During the 2-year study period, we had no turnover in faculty; did not pursue any formal marketing; did not change our surgical fees, billing system, or payer mix; and maintained our commitment to indigent care. RESULTS: After rebalancing our case mix, through procedural portfolio planning, average hospital operating income/procedure increased from $ 79 to $+816. Volume and diversity of cases increased, with no change in payer mix. Although charges/case decreased, both contribution margin and operating margin increased, due to improved throughput and decreased operating room times. The 5 most profitable procedures for the hospital were hernia repair, mandibular osteotomy, hand skin graft, free fibula flap, and head and neck flap, whereas the 5 least profitable were latissimus breast reconstruction, craniosynostosis repair, free-flap breast reconstruction, trunk skin graft, and cutaneous free flap. Total operating income for the hospital, from plastic surgery procedures, increased from $-115,103 to $+1,277,040, of which $350,000 (25%) was returned to the practice plan as enterprise funds to support program development. CONCLUSIONS: Through focused strategic initiatives, plastic surgeons and hospital administrators can work together to unlock the latent value of a plastic surgery service to an AMC. Specific financial benefits to the hospital include increased contribution margin and operating income, the latter of which can be reinvested in the plastic surgery service through a gain-sharing model. PMID- 27187255 TI - Implementation and Analysis of a Lean Six Sigma Program in Microsurgery to Improve Operative Throughput in Perforator Flap Breast Reconstruction. AB - PURPOSE: Perforator flaps have become a preferred method of breast reconstruction but can consume considerable resources. We examined the impact of a Six Sigma program on microsurgical breast reconstruction at an academic medical center. METHODS: Using methods developed by Motorola and General Electric, we applied critical pathway planning, workflow analysis, lean manufacturing, continuous quality improvement, and defect reduction to microsurgical breast reconstruction. Primary goals were to decrease preoperative-to-cut time and total operative time, through reduced variability and improved efficiency. Secondary goals were to reduce length of stay, complications, and reoperation. The project was divided into 3 phases: (1) Pre-Six Sigma (24 months), (2) Six Sigma (10 months), (3) and Post-Six Sigma (24 months). These periods (baseline, intervention, control) were compared by Student t test and chi analysis. RESULTS: Over a 5-year period, 112 patients underwent 168 perforator flaps for breast reconstructions, by experienced microsurgeons. Total operative time decreased from 714 to 607 minutes (P < 0.01), across the study period, with the greatest drop occurring in unilateral cases, from 672 to 498 minutes (P < 0.01). Length of stay decreased from 6.3 to 5.2 days (P = 0.01). Overall complication rates (35.9% vs 30%, not significant) and take-back rates (20.5% vs 23.9%, not significant) remained similar over the 5-year period. Physician revenue/minute increased from US $6.28 to US $7.59, whereas hospital revenue/minute increased from US $21.84 to US $25.11. CONCLUSIONS: A Six Sigma program in microsurgical breast reconstruction was associated with better operational and financial outcomes. These incremental gains were maintained over the course of the study, suggesting that these benefits were due, in part, to process improvements. However, continued reductions in total operative time and length of stay, well after the intervention period, support the possibility that "learning curve" phenomenon may have contributed to the improvement in these outcomes. PMID- 27187266 TI - Transcriptional reprogramming underpins enhanced plant growth promotion by the biocontrol fungus Trichoderma hamatum GD12 during antagonistic interactions with Sclerotinia sclerotiorum in soil. AB - The free-living soil fungus Trichoderma hamatum strain GD12 is notable amongst Trichoderma strains in both controlling plant diseases and stimulating plant growth, a property enhanced during its antagonistic interactions with pathogens in soil. These attributes, alongside its markedly expanded genome and proteome compared with other biocontrol and plant growth-promoting Trichoderma strains, imply a rich potential for sustainable alternatives to synthetic pesticides and fertilizers for the control of plant disease and for increasing yields. The purpose of this study was to investigate the transcriptional responses of GD12 underpinning its biocontrol and plant growth promotion capabilities during antagonistic interactions with the pathogen Sclerotinia sclerotiorum in soil. Using an extensive mRNA-seq study capturing different time points during the pathogen-antagonist interaction in soil, we show that dynamic and biphasic signatures in the GD12 transcriptome underpin its biocontrol and plant (lettuce) growth-promoting activities. Functional predictions of differentially expressed genes demonstrate the enrichment of transcripts encoding proteins involved in transportation and oxidation-reduction reactions during both processes and an over-representation of siderophores. We identify a biphasic response during biocontrol characterized by a significant induction of transcripts encoding small secreted cysteine-rich proteins, secondary metabolite-producing gene clusters and genes unique to GD12. These data support the hypothesis that Sclerotinia biocontrol is mediated by the synthesis and secretion of antifungal compounds and that GD12's unique reservoir of uncharacterized genes is actively recruited during the effective biological control of a plurivorous plant pathogen. PMID- 27187265 TI - The Role of Leukapheresis in the Current Management of Hyperleukocytosis in Newly Diagnosed Childhood Acute Lymphoblastic Leukemia. AB - BACKGROUND: Hyperleukocytosis in children with acute lymphoblastic leukemia (ALL) has been associated with early morbidity and mortality. The use of leukapheresis in these children treated with contemporary therapy remains controversial. PROCEDURE: We analyzed clinical data from patients enrolled onto frontline protocols for ALL (Total Therapy XV and XVI) between 2003 and 2014. We documented adverse events within the first 14 days in patients with a white blood cell (WBC) count >=200 * 10(9) /l and reviewed their management. RESULTS: Fifty-three (7.8%) of 678 consecutive pediatric patients with newly diagnosed ALL presented with hyperleukocytosis (median WBC count 393 * 10(9) /l; range 200-1,014). Two deaths in patients without initial hyperleukocytosis occurred within the first 2 weeks from diagnosis secondary to bacterial sepsis. A total of 21 (40%) patients with ALL and hyperleukocytosis developed grade 3 or 4 adverse events regardless of the use of leukapheresis (P > 0.99 and P = 0.19). Sixteen of 53 (30%) patients with ALL received low-dose chemotherapy for leukocytoreduction initially. One-third of patients received urate oxidase, and none of the patients with hyperleukocytosis required hemodialysis. CONCLUSIONS: The early morbidity and mortality commonly associated with hyperleukocytosis in children with newly diagnosed ALL can be avoided with contemporary supportive care and conservative management possibly obviating the need for costly and potentially dangerous leukapheresis. PMID- 27187267 TI - Preventing repetition of attempted suicide-III. The Amager Project, 5-year follow up of a randomized controlled trial. AB - BACKGROUND: The Amager Project was initiated as a quasi-experimental study in 2005, based on an active outreach suicide preventive intervention inspired by the Norwegian Baerum Model. A 1-year follow-up study was conducted as a randomized controlled trial showing that this kind of active outreach to suicide attempters had a significant preventive effect on the prevalence of suicide attempts and significantly reduced the number of patients repeating a suicide attempt. AIMS: In this 5-year RCT follow-up the aim was to investigate the sustainability of the suicide preventive effect shown in a 1-year follow-up study. METHOD: One hundred and thirty-three suicide attempters were included at this 5-year follow-up RCT study at Copenhagen University Hospital, Amager, and randomized to a rapid outreach suicide preventive intervention (OPAC) or TAU. RESULTS: Offering OPAC intervention to patients after a suicide attempt has a significant preventive effect on the total of suicide attempts and significantly reduces the number of patients repeating a suicide attempt. The suicide preventive effect lasts up to 265 weeks. After 3-4 years the effect on the number of patients repeating a suicide attempt is no longer sustainable, while the effect on the number of repetitive events remains significant. CONCLUSION: This study emphasizes the importance of a rapid and active outreach intervention and points out that the effect on the number of patients repeating a suicide attempt wears off and is no longer sustainable after 3-4 years, suggesting the need for a follow-up intervention. PMID- 27187270 TI - Mechanism of Rh-Catalyzed Oxidative Cyclizations: Closed versus Open Shell Pathways. AB - A conceptual theory for analyzing and understanding oxidative addition reactions that form the cornerstone of many transition metal mediated catalytic cycles that activate C-C and C-H bonds, for example, was developed. The cleavage of the sigma or pi-bond in the organic substrate can be envisioned to follow a closed or an open shell formalism, which is matched by a corresponding electronic structure at the metal center of the catalyst. Whereas the assignment of one or the other mechanistic scenario appears formal and equivalent at first sight, they should be recognized as different classes of reactions, because they lead to different reaction optimization and control strategies. The closed-shell mechanism involves heterolytic bond cleavages, which give rise to highly localized charges to form at the transition state. In the open-shell pathway, bonds are broken homolytically avoiding localized charges to accumulate on molecular fragments at the transition states. As a result, functional groups with inductive effects may exert a substantial influence on the energies of the intermediate and transition states, whereas no such effect is expected if the mechanism proceeds through the open-shell mechanism. If these functional groups are placed in a way that opens an electronic communication pathway to the molecular sites where charges accumulate, for example, using hyperconjugation, electron donating groups may stabilize a positive charge at that site. An instructive example is discussed, where this stereoelectronic effect allowed for rendering the oxidative addition diastereoselective. No such control is possible, however, when the open-shell reaction pathway is followed, because the inductive effects of functional groups have little to no effect on the stabilities of radical-like substrate states that are encountered when the bonds are broken in a homolytic fashion. Whether the closed-shell or open-shell mechanism for oxidative addition is followed is determined by the ordering of the d-orbital dominated frontier orbitals. If the highest occupied molecular orbital (HOMO) is oriented in space in such a way that will give the organic substrate easy access to the valence electron pair, the closed-shell mechanism can be followed. If the shape and orientation of the HOMO is not appropriate, however, an alternative pathway involving singlet excited states of the metal that will invoke the matching radicaloid cleavage of the organic substrate will dominate the oxidative addition. This novel paradigm for formally analyzing and understanding oxidative additions provides a new way of systematically understanding and planning catalytic reactions, as demonstrated by the in silico design of room-temperature Pauson-Khand reactions. PMID- 27187268 TI - Comparing three different measures of frailty in medical inpatients: Multicenter prospective cohort study examining 30-day risk of readmission or death. AB - BACKGROUND: Multiple tools are used to identify frailty. OBJECTIVE: To compare the global Clinical Frailty Scale (CFS) with more objective phenotypic tools (modified Fried score and the Timed Up and Go Test [TUGT]). DESIGN: Prospective cohort study. SETTING: General medical wards in Edmonton, Canada. PARTICIPANTS: Adults being discharged back to the community. MEASUREMENTS: All frailty assessments were done within 24 hours of discharge. Patients were classified as frail if they scored >=5 on the CFS and/or >=3 on the modified Fried score, and/or had reduced mobility (>20 seconds on the TUGT). The main outcome was readmission or death within 30 days. RESULTS: Of 495 patients, 211 (43%) were frail according to at least 1 assessment, 46 (9%) met all 3 frailty definitions, and 17% died or were readmitted to the hospital within 30 days. Although patients classified as frail on the CFS exhibited significantly higher 30-day readmission/death rates (23% vs 14% for not frail, P = 0.005; 28% vs. 12% in the elderly, P < 0.001), even after adjusting for age and sex (adjusted odds ratio [aOR]: 2.02, 95% confidence interval [CI]: 1.19-3.41 for all adults; aOR: 3.20, 95% CI: 1.55-6.60 for the elderly), patients meeting either of the phenotypic definitions for frailty but not the CFS definition were not at higher risk of 30 day readmission/death (aOR: 0.87, 95% CI: 0.34-2.19 for all adults and aOR: 1.41, 95% CI: 0.72-2.78 for the elderly). CONCLUSIONS: Frailty has a significant impact on postdischarge outcomes, and the CFS is the most useful of the frequently used frailty tools for predicting poor outcomes after discharge. Journal of Hospital Medicine 2016;11:556-562. (c) 2016 Society of Hospital Medicine. PMID- 27187271 TI - Phased-array ultrasound technology enhances accuracy of dual frequency ultrasound measurements - towards improved ultrasound bone diagnostics. AB - Overlying soft tissues attenuate ultrasound backscattered from bone, complicating diagnostics of osteoporosis at the most important fracture sites. Dual-frequency ultrasound technique (DFUS) has been proposed to solve this problem through determination of thickness and composition of overlying soft tissue. This study applies DFUS technique for the first time with a phased-array transducer to investigate if the thickness of two interfering layers (oil and water) can be accurately determined in a variety of configurations. Results indicate that DFUS may be used with phased-array ultrasound systems, making them a suitable combination to consider in future development of clinical in vivo ultrasound methodologies. PMID- 27187272 TI - Evaluating and Addressing the Leakage Problems of Black Carbon Mitigation in China's Domestic Sector. PMID- 27187275 TI - Research toward clinical wisdom. PMID- 27187274 TI - Neoadjuvant Sequential Docetaxel Followed by High-Dose Epirubicin in Combination With Cyclophosphamide Administered Concurrently With Trastuzumab. The DECT Trial. AB - To report the results of the DECT trial, a phase II study of locally advanced or operable HER2-positive breast cancer (BC) treated with taxanes and concurrent anthracyclines and trastuzumab. Eligible patients (stage IIA-IIIB HER2-positive BC, 18-75 years, normal organ functions, ECOG <=1, and left ventricular ejection fraction (LVEF) >=55%) received four cycles of neoadjuvant docetaxel, 100 mg/m(2) intravenously, plus trastuzumab 6 mg/kg (loading dose 8 mg/kg) every 3 weeks, followed by four 3-weekly cycles of epirubicin 120 mg/m(2) and cyclophosphamide, 600 mg/m(2) , plus trastuzumab. Primary objective was pathologic complete response (pCR) rate, defined as ypT0/is ypN0 at definitive surgery. We enrolled 45 consecutive patients. All but six patients (13.3%) completed chemotherapy and all underwent surgery. pCR was observed in 28 patients (62.2%) overall and in 6 (66.7%) from the inflammatory subgroup. The classification and regression tree analysis showed a 100% pCR rate in patients with BMI >=25 and with hormone negative disease. The median follow up was 46 months (8-78). Four-year recurrence free survival was 74.7% (95%CI, 58.2-91.2). Seven patients (15.6%) recurred and one died. Treatment was well tolerated, with limiting toxicity being neutropenia. No clinical cardiotoxicity was observed. Six patients (13.4%) showed a transient LVEF decrease (<10%). In one patient we observed a >=10% asymptomatic LVEF decrease persisting after surgery. Notwithstanding their limited applicability due to the current guidelines, our findings support the efficacy of the regimen of interest in the neoadjuvant setting along with a fairly acceptable toxicity profile, including cardiotoxicity. Results on BMI may invite further assessment in future studies. J. Cell. Physiol. 231: 2541-2547, 2016. (c) 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. PMID- 27187276 TI - Are senior nurses on Clinical Commissioning Groups in England inadvertently supporting the devaluation of their profession?: A critical integrative review of the literature. AB - In this study, we discuss the role of senior nurses who sit on clinical commissioning groups that now plan and procure most health services in England. These nurses are expected to bring a nursing view to all aspects of clinical commissioning group business. The role is a senior level appointment and requires experience of strategic commissioning. However, little is known about how nurses function in these roles. Following Barrientos' methodology, published policy and literature were analysed to investigate these roles and National Health Service England's claim that nursing can influence and advance a nursing perspective in clinical commissioning groups. Drawing on work by Berg, Barry and Chandler on 'new public management', we discuss how nurses on clinical commissioning groups work at the alignment of the interests of biomedicine and managerialism. We propose that the way this nursing role is being implemented might paradoxically offer further evidence of the devaluing of nursing rather than the emergence of a strong professional nursing voice at the level of strategic commissioning. PMID- 27187277 TI - A novel small-molecule PPI inhibitor targeting integrin alphavbeta3-osteopontin interface blocks bone resorption in vitro and prevents bone loss in mice. AB - Small molecule-inhibition targeting protein-protein interaction (PPI) is now recognized as an emerging and challenging area in drug design. We developed a novel interactive drug discovery methodology known as Protein Chip technology (ProteoChip) as a cutting-edge PPI assay system applicable for unique PPI targeting therapeutics integrated with computer-aided drug design (CADD). Here, we describe a novel small molecular PPI inhibitor, IPS-02001, which the blocks integrin alphavbeta3-osteopontin interface a novel PPI inhibitor identified by the interactive methodology of both ProteoChip- and CADD-based PPI assay. IPS 02001 (6,7-Dichloro-2,3,5,8-tetrahydroxy-1,4-naphthoquinone) was screened from different compound libraries (InterBioScreen, Commercial libraries) using an in silico structure-based molecular docking simulation method and a protein chip based protein-protein interaction assay system. Additionally, integrin alphavbeta3, an adhesion receptor expressed in osteoclasts (OCs), was implicated in the regulation of OC function via regulation of the cytoskeletal organization of OCs. IPS-02001 blocked OC maturation from murine bone marrow-derived macrophages, as well as the resorptive function of OCs. Moreover, treatment with IPS-02001 impaired downstream signaling of integrin alphavbeta3 linked to Pyk2, c Src, PLCgamma2, and Vav3 and disrupted the actin cytoskeleton in mature OCs. Furthermore, IPS-02001 blocked RANKL-induced bone destruction by reducing the number of OCs and protected against ovariectomy-induced bone loss in mice. Thus, IPS-02001 may represent a promising new class of anti-resorptive drugs for treatment of bone diseases associated with increased OC function. PMID- 27187278 TI - Ferritin-mediated siRNA delivery and gene silencing in human tumor and primary cells. AB - We demonstrate a straightforward method to encapsulate siRNA into naturally available and unmodified human apoferritin. The encapsulation into apoferritin is independent of the sequence of the siRNA and provides superior protection for those sensitive molecules. High efficiency in transfection can be achieved in human tumorigenic cells, human primary mesenchymal stem cells (hMSC) and peripheral blood mononuclear cells (PBMCs). In contrast to Lipofectamine, highly effective gene silencing can be achieved with ferritin as the delivery agent in both tumor cells and PBMCs at low siRNA concentrations (10 nM). As an endogenous delivery agent, apoferritin does not induce immune activation of T- and B-cells in human PBMCs. Apoferritin shows intrinsic anti-inflammatory effects and apoferritin-mediated delivery shows a preference for immune-activated T- and B cells, a natural selectivity which may turn useful for drug delivery in case of infections or inflammatory diseases. PMID- 27187273 TI - Promiscuity in the Enzymatic Catalysis of Phosphate and Sulfate Transfer. AB - The enzymes that facilitate phosphate and sulfate hydrolysis are among the most proficient natural catalysts known to date. Interestingly, a large number of these enzymes are promiscuous catalysts that exhibit both phosphatase and sulfatase activities in the same active site and, on top of that, have also been demonstrated to efficiently catalyze the hydrolysis of other additional substrates with varying degrees of efficiency. Understanding the factors that underlie such multifunctionality is crucial both for understanding functional evolution in enzyme superfamilies and for the development of artificial enzymes. In this Current Topic, we have primarily focused on the structural and mechanistic basis for catalytic promiscuity among enzymes that facilitate both phosphoryl and sulfuryl transfer in the same active site, while comparing this to how catalytic promiscuity manifests in other promiscuous phosphatases. We have also drawn on the large number of experimental and computational studies of selected model systems in the literature to explore the different features driving the catalytic promiscuity of such enzymes. Finally, on the basis of this comparative analysis, we probe the plausible origins and determinants of catalytic promiscuity in enzymes that catalyze phosphoryl and sulfuryl transfer. PMID- 27187279 TI - CD44 alternative splicing in gastric cancer cells is regulated by culture dimensionality and matrix stiffness. AB - Two-dimensional (2D) cultures often fail to mimic key architectural and physical features of the tumor microenvironment. Advances in biomaterial engineering allow the design of three-dimensional (3D) cultures within hydrogels that mimic important tumor-like features, unraveling cancer cell behaviors that would not have been observed in traditional 2D plastic surfaces. This study determined how 3D cultures impact CD44 alternative splicing in gastric cancer (GC) cells. In 3D cultures, GC cells lost expression of the standard CD44 isoform (CD44s), while gaining CD44 variant 6 (CD44v6) expression. This splicing switch was reversible, accelerated by nutrient shortage and delayed at lower initial cell densities, suggesting an environmental stress-induced response. It was further shown to be dependent on the hydrogel matrix mechanical properties and accompanied by the upregulation of genes involved in epithelial-mesenchymal transition (EMT), metabolism and angiogenesis. The 3D cultures reported here revealed the same CD44 alternative splicing pattern previously observed in human premalignant and malignant gastric lesions. These findings indicate that fundamental features of 3D cultures - such as soluble factors diffusion and mechanical cues - influence CD44 expression in GC cells. Moreover, this study provides a new model system to study CD44 dysfunction, whose role in cancer has been in the spotlight for decades. PMID- 27187280 TI - Pentamethylcyclopentadienyl Half-Sandwich Diazoalkane Complexes of Ruthenium: Preparation and Reactivity. AB - The diazoalkane complexes [Ru(eta(5)-C5Me5)(N2CAr1Ar2){P(OR)3}L]BPh4 (1-4) [R = Me, L = P(OMe)3 (1); R = Et, L = P(OEt)3 (2); R = Me, L = PPh3 (3); R = Et, L = PPh3 (4); Ar1 = Ar2 = Ph (a); Ar1 = Ph, Ar2 = p-tolyl (b); Ar1Ar2 = C12H8 (c); Ar1 = Ph, Ar2 = PhC(O) (d)] and [Ru(eta(5) C5Me5){N2C(C12H8)}{PPh(OEt)2}(PPh3)]BPh4 (5c) were prepared by allowing chloro compounds RuCl(eta(5)-C5Me5)[P(OR)3]L to react with the diazoalkane Ar1Ar2CN2 in the presence of NaBPh4. Treatment of complexes 1-4 with H2O afforded 1,2-diazene derivatives [Ru(eta(5)-C5Me5)(eta(2)-NH?NH){P(OR)3}L]BPh4 (6-9) and ketone Ar1Ar2CO. A reaction path involving nucleophilic attack by H2O on the coordinated diazoalkane is proposed and supported by density functional theory calculations. The complexes were characterized spectroscopically (IR and (1)H, (31)P, (13)C, (15)N NMR) and by X-ray crystal structure determination of [Ru(eta(5) C5Me5)(N2CC12H8){P(OEt)3}2]BPh4 (2c) and [Ru(eta(5)-C5Me5)(eta(2) NH?NH){P(OEt)3}2]BPh4 (7). PMID- 27187285 TI - Covered Wagon: Bror Julius Olsson Nordfeldt. PMID- 27187282 TI - Changes in Corneal Biomechanical Properties after Long-Term Topical Prostaglandin Therapy. AB - OBJECTIVE: To compare corneal biomechanical properties, measured by a newly developed tonometer (Corneal Visualization Scheimpflug Technology, Corvis ST), in untreated primary open angle glaucoma (POAG) patients, POAG patients with long term topical prostaglandin analog (PGA) therapy and in normal controls. Further is to investigate the potential effects of PGA on corneal biomechanics. METHODS: In this case-control study, 35 consecutive medication naive eyes with POAG, 34 POAG eyes with at least 2 years treatment by PGA and 19 normal eyes were included. Intraocular pressure (IOP), central corneal thickness (CCT) and corneal biomechanical parameters, including deformation amplitude (DA), applanation time (AT1 and AT2), applanation length (AL1 and AL2), applanation velocity (AV1 and AV2), and peak distance and radius were measured using Corvis ST. Axial length and corneal curvature were measured with partial coherence interferometry (IOLMaster, Zeiss, Germany). General linear model analysis was performed to investigate the corneal biomechanical property changes among the normal controls, newly diagnosed POAG patients and POAG patients with long-term PGA treatment, and among the subgroups of different types of PGA treatment, including bimatoprost, latanoprost and travoprost. Furthermore, pairwise comparisons using Bonferroni correction for least squares means were employed. RESULTS: AT1 (p<0.0001), AV1 (p<0.0001), AT2 (p = 0.0001), AV2 (p<0.0001) and DA (p = 0.0004) in newly diagnosed glaucoma patients were significantly different from those in normal subjects and in patients underwent at least 2 years topical PGA therapy after adjusting for age and gender. After adjusting for age, gender, IOP, CCT, axial length and corneal curvature, a significant difference was detected for DA between glaucoma patients without PGA treatment and patients with long-term PGA therapy (p = 0.0387). Furthermore, there were no statistical significant differences in all of the corneal biomechanical parameters among the 3 types of PGA therapy subgroups, namely bimatoprost, latanoprost and travoprost. CONCLUSIONS: Significant changes in corneal deformation parameters were found among untreated POAG patients, POAG patients with long-term topical PGA therapy and normal controls. Long-term topical PGA treatment might have a direct effect on corneal biomechanical properties in addition to the indirect effect owing to the PGA-induced IOP reduction and CCT decrease on corneal dynamic properties. PMID- 27187286 TI - Lead in the Water: A Tale of Social and Environmental Injustice. PMID- 27187294 TI - Evidence-Based, Reality-Driven Colorectal Cancer Screening Guidelines: The Critical Relationship of Adherence to Effectiveness. PMID- 27187295 TI - Utility of Cancer Value Frameworks for Patients, Payers, and Physicians. PMID- 27187296 TI - A PIECE OF MY MIND. My Name Is Not "Interpreter". PMID- 27187297 TI - Toward a Patient-Centered Value Framework in Oncology. PMID- 27187298 TI - Communication With Family Caregivers in the Intensive Care Unit: Answers and Questions. PMID- 27187299 TI - Turning the Pathogenesis of Acute Peptic Esophagitis Inside Out. PMID- 27187300 TI - Effect of Early Prophylactic High-Dose Recombinant Human Erythropoietin in Very Preterm Infants on Neurodevelopmental Outcome at 2 Years: A Randomized Clinical Trial. AB - IMPORTANCE: Very preterm infants are at risk of developing encephalopathy of prematurity and long-term neurodevelopmental delay. Erythropoietin treatment is neuroprotective in animal experimental and human clinical studies. OBJECTIVE: To determine whether prophylactic early high-dose recombinant human erythropoietin (rhEPO) in preterm infants improves neurodevelopmental outcome at 2 years' corrected age. DESIGN, SETTING, AND PARTICIPANTS: Preterm infants born between 26 weeks 0 days' and 31 weeks 6 days' gestation were enrolled in a randomized, double-blind, placebo-controlled, multicenter trial in Switzerland between 2005 and 2012. Neurodevelopmental assessments at age 2 years were completed in 2014. INTERVENTIONS: Participants were randomly assigned to receive either rhEPO (3000 IU/kg) or placebo (isotonic saline, 0.9%) intravenously within 3 hours, at 12 to 18 hours, and at 36 to 42 hours after birth. MAIN OUTCOMES AND MEASURES: Primary outcome was cognitive development assessed with the Mental Development Index (MDI; norm, 100 [SD, 15]; higher values indicate better function) of the Bayley Scales of Infant Development, second edition (BSID-II) at 2 years corrected age. The minimal clinically important difference between groups was 5 points (0.3 SD). Secondary outcomes were motor development (assessed with the Psychomotor Development Index), cerebral palsy, hearing or visual impairment, and anthropometric growth parameters. RESULTS: Among 448 preterm infants randomized (mean gestational age, 29.0 [range, 26.0-30.9] weeks; 264 [59%] female; mean birth weight, 1210 [range, 490-2290] g), 228 were randomized to rhEPO and 220 to placebo. Neurodevelopmental outcome data were available for 365 (81%) at a mean age of 23.6 months. In an intention-to-treat analysis, mean MDI was not statistically significantly different between the rhEPO group (93.5 [SD, 16.0] [95% CI, 91.2 to 95.8]) and the placebo group (94.5 [SD, 17.8] [95% CI, 90.8 to 98.5]) (difference, -1.0 [95% CI, -4.5 to 2.5]; P = .56). No differences were found between groups in the secondary outcomes. CONCLUSIONS AND RELEVANCE: Among very preterm infants who received prophylactic early high-dose rhEPO for neuroprotection, compared with infants who received placebo, there were no statistically significant differences in neurodevelopmental outcomes at 2 years. Follow-up for cognitive and physical problems that may not become evident until later in life is required. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00413946. PMID- 27187301 TI - Prevalence of and Factors Related to Discordance About Prognosis Between Physicians and Surrogate Decision Makers of Critically Ill Patients. AB - IMPORTANCE: Misperceptions about prognosis by individuals making decisions for incapacitated critically ill patients (surrogates) are common and often attributed to poor comprehension of medical information. OBJECTIVE: To determine the prevalence of and factors related to physician-surrogate discordance about prognosis in intensive care units (ICUs). DESIGN, SETTING, AND PARTICIPANTS: Mixed-methods study comprising quantitative surveys and qualitative interviews conducted in 4 ICUs at a major US medical center involving surrogate decision makers and physicians caring for patients at high risk of death from January 4, 2005, to July 10, 2009. MAIN OUTCOMES AND MEASURES: Discordance about prognosis, defined as a difference between a physician's and a surrogate's prognostic estimates of at least 20%; misunderstandings by surrogates (defined as any difference between a physician's prognostic estimate and a surrogate's best guess of that estimate); differences in belief (any difference between a surrogate's actual estimate and their best guess of the physician's estimate). RESULTS: Two hundred twenty-nine surrogate decision makers (median age, 47 [interquartile range {IQR}, 35-56] years; 68% women) and 99 physicians were involved in the care of 174 critically ill patients (median age, 60 [IQR, 47-74] years; 44% women). Physician-surrogate discordance about prognosis occurred in 122 of 229 instances (53%; 95% CI, 46.8%-59.7%). In 65 instances (28%), discordance was related to both misunderstandings by surrogates and differences in belief about the patient's prognosis; 38 (17%) were related to misunderstandings by surrogates only; 7 (3%) were related to differences in belief only; and data were missing for 12. Seventy-five patients (43%) died. Surrogates' prognostic estimates were much more accurate than chance alone, but physicians' prognostic estimates were statistically significantly more accurate than surrogates' (C statistic, 0.83 vs 0.74; absolute difference, 0.094; 95% CI, 0.024-0.163; P = .008). Among 71 surrogates interviewed who had beliefs about the prognosis that were more optimistic than that of the physician, the most common reasons for optimism were a need to maintain hope to benefit the patient (n = 34), a belief that the patient had unique strengths unknown to the physician (n = 24), and religious belief (n = 19). CONCLUSIONS AND RELEVANCE: Among critically ill patients, discordant expectations about prognosis were common between patients' physicians and surrogate decision makers and were related to misunderstandings by surrogates about physicians' assessments of patients' prognoses and differences in beliefs about patients' prognoses. PMID- 27187302 TI - Association of Hospital Critical Access Status With Surgical Outcomes and Expenditures Among Medicare Beneficiaries. AB - IMPORTANCE: Critical access hospitals are a predominant source of care for many rural populations. Previous reports suggest these centers provide lower quality of care for common medical admissions. Little is known about the outcomes and costs of patients admitted for surgical procedures. OBJECTIVE: To compare the surgical outcomes and associated Medicare payments at critical access hospitals vs non-critical access hospitals. DESIGN, SETTING, AND PARTICIPANTS: Cross sectional retrospective review of 1,631,904 Medicare beneficiary admissions to critical access hospitals (n = 828) and non-critical access hospitals (n = 3676) for 1 of 4 common types of surgical procedures-appendectomy, 3467 for critical access and 151,867 for non-critical access; cholecystectomy, 10,556 for critical access and 573,435 for non-critical access; colectomy, 10,198 for critical access and 577,680 for non-critical access; hernia repair, 4291 for critical access and 300,410 for non-critical access-between 2009 and 2013. We compared risk-adjusted outcomes using a multivariable logistical regression that adjusted for patient factors (age, sex, race, Elixhauser comorbidities), admission type (elective, urgent, emergency), and type of operation. EXPOSURES: Undergoing surgical procedures at critical access vs non-critical access hospitals. MAIN OUTCOMES AND MEASURES: Thirty-day mortality, postoperative serious complications (eg, myocardial infarction, pneumonia, or acute renal failure and a length of stay >75th percentile). Hospital costs were assessed using price-standardized Medicare payments during hospitalization. RESULTS: Patients (mean age, 76.5 years; 56.2% women) undergoing surgery at critical access hospitals were less likely to have chronic medical problems, and they had lower rates of heart failure (7.7% vs 10.7%, P < .0001), diabetes (20.2% vs 21.7%, P < .001), obesity (6.5% vs 10.6%, P < .001), or multiple comorbid diseases (% of patients with >=2 comorbidities; 60.4% vs 70.2%, P < .001). After adjustment for patient factors, critical access and non-critical access hospitals had no statistically significant differences in 30-day mortality rates (5.4% vs 5.6%; adjusted odds ratio [OR], 0.96; 95% confidence interval [CI], 0.89-1.03; P = .28). However, critical access vs non critical access hospitals had significantly lower rates of serious complications (6.4% vs 13.9%; OR, 0.35; 95% CI, 0.32-0.39; P < .001). Medicare expenditures adjusted for patient factors and procedure type were lower at critical access hospitals than non-critical access hospitals ($14,450 vs $15,845; difference, $1395, P < .001). CONCLUSIONS AND RELEVANCE: Among Medicare beneficiaries undergoing common surgical procedures, patients admitted to critical access hospitals compared with non-critical access hospitals had no significant difference in 30-day mortality rates, decreased risk-adjusted serious complication rates, and lower-adjusted Medicare expenditures, but were less medically complex. PMID- 27187304 TI - Accurately Measuring Hospital Venous Thromboembolism Prevention Efforts. PMID- 27187303 TI - Association of Acute Gastroesophageal Reflux Disease With Esophageal Histologic Changes. AB - IMPORTANCE: The histologic changes associated with acute gastroesophageal reflux disease (GERD) have not been studied prospectively in humans. Recent studies in animals have challenged the traditional notion that reflux esophagitis develops when esophageal surface epithelial cells are exposed to lethal chemical injury from refluxed acid. OBJECTIVE: To evaluate histologic features of esophageal inflammation in acute GERD to study its pathogenesis. DESIGN, SETTING, AND PARTICIPANTS: Patients from the Dallas Veterans Affairs Medical Center who had reflux esophagitis successfully treated with proton pump inhibitors (PPIs) began 24-hour esophageal pH and impedance monitoring and esophagoscopy (including confocal laser endomicroscopy [CLE]) with biopsies from noneroded areas of distal esophagus at baseline (taking PPIs) and at 1 week and 2 weeks after stopping the PPI medication. Enrollment began May 2013 and follow-up ended July 2015. INTERVENTIONS: PPIs stopped for 2 weeks. MAIN OUTCOMES AND MEASURES: Twelve patients (men, 11; mean age, 57.6 year [SD, 13.1]) completed the study. Primary outcome was change in esophageal inflammation 2 weeks after stopping the PPI medication, determined by comparing lymphocyte, eosinophil, and neutrophil infiltrates (each scored on a 0-3 scale) in esophageal biopsies. Also evaluated were changes in epithelial basal cell and papillary hyperplasia, surface erosions, intercellular space width, endoscopic grade of esophagitis, esophageal acid exposure, and mucosal impedance (an index of mucosal integrity). RESULTS: At 1 week and 2 weeks after discontinuation of PPIs, biopsies showed significant increases in intraepithelial lymphocytes, which were predominantly T cells (median [range]: 0 (0-2) at baseline vs 1 (1-2) at both 1 week [P = .005] and 2 weeks [P = .002]); neutrophils and eosinophils were few or absent. Biopsies also showed widening of intercellular spaces (confirmed by CLE), and basal cell and papillary hyperplasia developed without surface erosions. Two weeks after stopping the PPI medication, esophageal acid exposure increased (median: 1.2% at baseline to 17.8% at 2 weeks; Delta, 16.2% [95% CI, 4.4%-26.5%], P = .005), mucosal impedance decreased (mean: 2671.3 Omega at baseline to 1508.4 Omega at 2 weeks; Delta, 1162.9 Omega [95% CI, 629.9-1695.9], P = .001), and all patients had evidence of esophagitis. CONCLUSIONS AND RELEVANCE: In this preliminary study of 12 patients with severe reflux esophagitis successfully treated with PPI therapy, stopping PPI medication was associated with T lymphocyte-predominant esophageal inflammation and basal cell and papillary hyperplasia without loss of surface cells. If replicated, these findings suggest that the pathogenesis of reflux esophagitis may be cytokine-mediated rather than the result of chemical injury. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01733810. PMID- 27187305 TI - Surveillance Imaging in Patients in Remission From Hodgkin and Diffuse Large B Cell Lymphoma. PMID- 27187306 TI - Which Oral Anticoagulant for Atrial Fibrillation? PMID- 27187308 TI - Early Azithromycin Treatment to Prevent Severe Lower Respiratory Tract Illnesses in Children. PMID- 27187307 TI - Sexual Harassment and Discrimination Experiences of Academic Medical Faculty. PMID- 27187309 TI - Early Azithromycin Treatment to Prevent Severe Lower Respiratory Tract Illnesses in Children--Reply. PMID- 27187310 TI - Leprosy as a Cause of Distal Symmetric Polyneuropathy. PMID- 27187311 TI - Leprosy as a Cause of Distal Symmetric Polyneuropathy--Reply. PMID- 27187312 TI - Firearm Access and Risk of Suicide. PMID- 27187313 TI - Firearm Access and Risk of Suicide--Reply. PMID- 27187314 TI - Error in Text. PMID- 27187315 TI - Error in Collaborator Name. PMID- 27187317 TI - Tests in the Diagnosis of Cancer. PMID- 27187318 TI - JAMA PATIENT PAGE. Preventing Venous Thromboembolism After Surgery. PMID- 27187319 TI - Using Bayesian Nonparametric Hidden Semi-Markov Models to Disentangle Affect Processes during Marital Interaction. AB - Sequential affect dynamics generated during the interaction of intimate dyads, such as married couples, are associated with a cascade of effects-some good and some bad-on each partner, close family members, and other social contacts. Although the effects are well documented, the probabilistic structures associated with micro-social processes connected to the varied outcomes remain enigmatic. Using extant data we developed a method of classifying and subsequently generating couple dynamics using a Hierarchical Dirichlet Process Hidden semi Markov Model (HDP-HSMM). Our findings indicate that several key aspects of existing models of marital interaction are inadequate: affect state emissions and their durations, along with the expected variability differences between distressed and nondistressed couples are present but highly nuanced; and most surprisingly, heterogeneity among highly satisfied couples necessitate that they be divided into subgroups. We review how this unsupervised learning technique generates plausible dyadic sequences that are sensitive to relationship quality and provide a natural mechanism for computational models of behavioral and affective micro-social processes. PMID- 27187320 TI - Improvement of quality of life and menopausal symptoms in climacteric women treated with low-dose monthly parenteral formulations of non-polymeric microspheres of 17beta-estradiol/progesterone. AB - OBJECTIVE: To evaluate the short term effect over menopausal symptoms and quality of life (QoL) of monthly parenteral formulations of 17beta-estradiol (E)/progesterone (P) non-polymeric microspheres. METHODS: This is a secondary analysis of a multicenter, randomized, single-blinded study that included peri- and post-menopausal symptomatic women assigned to receive a monthly intramuscular injection of 0.5 mg E + 15 mg P (Group A, n = 34), 1 mg E + 20 mg P (Group B, n = 24), or 1 mg E + 30 mg P (Group C, n = 26) for 6 months. Intensity of menopausal symptoms was assessed before and after treatment with the Greene Climacteric Scale (GCS) and QoL with the Utian Quality of Life Scale (UQoLS). RESULTS: Menopausal symptoms improved for all groups at six months evidenced by lower cluster/sub-cluster GCS scores. Equally, there was an overall trend for QoL improvement for all groups evidenced by higher domain UQoLS scores at six months; but only significant for the emotional (Groups A and B) and occupational domains (Groups A and C). CONCLUSION: The three low-dose continuous sequential intramuscular monthly formulations of E/P microspheres exerted a positive effect over menopausal symptoms and QoL. Long-term research is warranted with these formulations. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov Identifiers NCT 00775242. PMID- 27187322 TI - Identification and Synthesis of (Z,Z)-8,11-Heptadecadienyl Formate and (Z)-8 Heptadecenyl Formate: Unsaturated Aliphatic Formates Found in the Unidentified Astigmatid Mite, Sancassania sp. Sasagawa (Acari: Acaridae). AB - We identified two aliphatic formates, (Z,Z)-8,11-heptadecadienyl formate and (Z) 8-heptadecenyl formate in the opisthonotal gland secretions of an unidentified acarid species, namely Sancassania sp. Sasagawa. Both compounds were isolated using silica gel column chromatography and the structures were elucidated by 1H NMR and GC/FT-IR. Further information on the double bond positions was obtained by GC-MS analysis of the corresponding dimethyl disulfide derivatives. Based on the estimated structures of the two formates and using linoleic and oleic acids as the respective starting materials, a simple four-step synthesis was achieved via Barton decarboxylation as the key step. The aliphatic formates identified in acarids thus far are neryl formate ((Z)-3,7-dimethylocta-2,6-dienyl formate) and lardolure (1,3,5,7-tetramethyldecyl formate), and both have been reported to have pheromone functions. The biological function of the two formates isolated in this study is currently being investigated. Although we can speculate that the two compounds were biosynthesized from linoleic and oleic acid, there is a possibility that the synthetic processes featured a novel chain shortening and formic acid esterification mechanism. PMID- 27187321 TI - Synthesis and Biological Testing of Novel Glucosylated Epigallocatechin Gallate (EGCG) Derivatives. AB - Epigallocatechin gallate (EGCG) is the most abundant component of green tea catechins and has strong physiological activities. In this study, two novel EGCG glycosides (EGCG-G1 and EGCG-G2) were chemoselectively synthesized by a chemical modification strategy. Each of these EGCG glycosides underwent structure identification, and the structures were assigned as follows: epigallocatechin gallate-4''-O-beta-d-glucopyranoside (EGCG-G1, 2) and epigallocatechin gallate 4',4''-O-beta-d-gluco-pyranoside (EGCG-G2, 3). The EGCG glycosides were evaluated for their anticancer activity in vitro against two human breast cell lines (MCF-7 and MDA-MB-231) using MTT assays. The inhibition rate of EGCG glycosides (EGCG-G1 and EGCG-G2) is not obvious. The EGCG glycosides are more stable than EGCG in aqueous solutions, but exhibited decreasing antioxidant activity in the DPPH radical-scavenging assay (EGCG > EGCG-G2 > EGCG-G1). Additionally, the EGCG glycosides exhibited increased water solubility: EGCG-G2 and EGCG-G1 were 15 and 31 times as soluble EGCG, respectively. The EGCG glycosides appear to be useful, and further studies regarding their biological activity are in progress. PMID- 27187323 TI - Inhibitors of the Hydrolytic Enzyme Dimethylarginine Dimethylaminohydrolase (DDAH): Discovery, Synthesis and Development. AB - Dimethylarginine dimethylaminohydrolase (DDAH) is a highly conserved hydrolytic enzyme found in numerous species, including bacteria, rodents, and humans. In humans, the DDAH-1 isoform is known to metabolize endogenous asymmetric dimethylarginine (ADMA) and monomethyl arginine (l-NMMA), with ADMA proposed to be a putative marker of cardiovascular disease. Current literature reports identify the DDAH family of enzymes as a potential therapeutic target in the regulation of nitric oxide (NO) production, mediated via its biochemical interaction with the nitric oxide synthase (NOS) family of enzymes. Increased DDAH expression and NO production have been linked to multiple pathological conditions, specifically, cancer, neurodegenerative disorders, and septic shock. As such, the discovery, chemical synthesis, and development of DDAH inhibitors as potential drug candidates represent a growing field of interest. This review article summarizes the current knowledge on DDAH inhibition and the derived pharmacokinetic parameters of the main DDAH inhibitors reported in the literature. Furthermore, current methods of development and chemical synthetic pathways are discussed. PMID- 27187324 TI - Efficient Synthesis of the Lewis A Tandem Repeat. AB - The convergent synthesis of the Lewis A (Le(a)) tandem repeat is described. The Le(a) tandem repeat is a carbohydrate ligand for a mannose binding protein that shows potent inhibitory activity against carcinoma growth. The Le(a) unit, {beta d-Gal-(1->3)-[alpha-l-Fuc-(1->4)]-beta-d-GlcNAc}, was synthesized by stereoselective nitrile-assisted beta-galactosylation with the phenyl 3-O-allyl 2,4,6-tri-O-benzyl-1-thio-beta-galactoside, and ether-assisted alpha-fucosylation with fucosyl (N-phenyl)trifluoroacetimidate. This common Le(a) unit was easily converted to an acceptor and donor in high yields, and the stereoselective assembly of the hexasaccharide and dodecasaccharide as the Le(a) tandem repeat framework was achieved by 2-trichloroacetamido-assisted beta-glycosylation and the (N-phenyl)trifluoroacetimidate method. PMID- 27187325 TI - The Effect of Phenazine-1-Carboxylic Acid on the Morphological, Physiological, and Molecular Characteristics of Phellinus noxius. AB - In this study, the effect of phenazine-1-carboxylic acid (PCA) on morphological, physiological, and molecular characteristics of Phellinus noxius has been investigated, and the potential antifungal mechanism of PCA against P. noxius was also explored. The results revealed that PCA showed in vitro antifungal potential against P. noxius and completely inhibited P. noxius hyphae at concentrations >40 MUg/mL. PCA inhibited both mycelial growth and the loss of mycelial biomass in vitro in a dose-dependent manner. Morphological changes in PCA-treated P. noxius hyphae, such as irregularly swollen mycelia as well as short hyphae with increased septation and less branching, were observed by optical microscopy. The intracellular reactive oxygen species (ROS) levels were significantly increased in PCA-treated P. noxius cells as compared to control groups. Induced hyperpolarization of the mitochondrial membrane potential (MMP), repressed superoxide dismutase (SOD) activity and up-regulated gene expression of seven tested genes were also found in PCA-treated P. noxius groups. Thus, the present results suggested that the mechanism of action of PCA against P. noxius might be attributed to direct damage of mycelium and high intracellular ROS production, and indirect induction of genes involved in cell detoxification, oxidation reduction process, and electron transport of the respiratory chain. PMID- 27187327 TI - Preparation of Pd/Bacterial Cellulose Hybrid Nanofibers for Dopamine Detection. AB - Palladium nanoparticle-bacterial cellulose (PdBC) hybrid nanofibers were synthesized by in-situ chemical reduction method. The obtained PdBC nanofibers were characterized by a series of analytical techniques. The results revealed that Pd nanoparticles were evenly dispersed on the surfaces of BC nanofibers. Then, the as-prepared PdBC nanofibers were mixed with laccase (Lac) and Nafion to obtain mixture suspension, which was further modified on electrode surface to construct novel biosensing platform. Finally, the prepared electrochemical biosensor was employed to detect dopamine. The analysis result was satisfactory, the sensor showed excellent electrocatalysis towards dopamine with high sensitivity (38.4 uA.mM(-1)), low detection limit (1.26 uM), and wide linear range (5-167 uM). Moreover, the biosensor also showed good repeatability, reproducibility, selectivity and stability and was successfully used in the detection of dopamine in human urine, thus providing a promising method for dopamine analysis in clinical application. PMID- 27187326 TI - Discovery of Potent c-MET Inhibitors with New Scaffold Having Different Quinazoline, Pyridine and Tetrahydro-Pyridothienopyrimidine Headgroups. AB - Cellular mesenchymal-epithelial transition factor (c-MET) is closely linked to human malignancies, which makes it an important target for treatment of cancer. In this study, a series of 3-methoxy-N-phenylbenzamide derivatives, N-(3-(tert butyl)-1-phenyl-1H-pyrazol-5-yl) benzamide derivatives and N1-(3-fluoro-4 methoxyphenyl)-N3-(4-fluorophenyl) malonamide derivatives were designed and synthesized, some of them were identified as c-MET inhibitors. Among these compounds with new scaffolds having different quinazoline, pyridine and tetrahydro-pyridothienopyrimidine head groups, compound 11c, 11i, 13b, 13h exhibited both potent inhibitory activities against c-MET and high anticancer activity against tested cancer cell lines in vitro. In addition, kinase selectivity assay further demonstrated that both 13b and 13h are potent and selective c-MET inhibitors. Molecular docking supported that they bound well to c MET and VEGFR2, which demonstrates that they are potential c-MET RTK inhibitors for cancer therapy. PMID- 27187328 TI - Anti-Inflammatory Applications of Melittin, a Major Component of Bee Venom: Detailed Mechanism of Action and Adverse Effects. AB - Inflammation is a pervasive phenomenon triggered by the innate and adaptive immune systems to maintain homeostasis. The phenomenon normally leads to recovery from infection and healing, but when not properly phased, inflammation may cause immune disorders. Bee venom is a toxin that bees use for their protection from enemies. However, for centuries it has been used in the Orient as an anti inflammatory medicine for the treatment of chronic inflammatory diseases. Bee venom and its major component, melittin, are potential means of reducing excessive immune responses and provide new alternatives for the control of inflammatory diseases. Recent experimental studies show that the biological functions of melittin could be applied for therapeutic use in vitro and in vivo. Reports verifying the therapeutic effects of melittin are accumulating in the literature, but the cellular mechanism(s) of the anti-inflammatory effects of melittin are not fully elucidated. In the present study, we review the current knowledge on the therapeutic effects of melittin and its detailed mechanisms of action against several inflammatory diseases including skin inflammation, neuroinflammation, atherosclerosis, arthritis and liver inflammation, its adverse effects as well as future prospects regarding the use of melittin. PMID- 27187329 TI - Antimicrobial Activity of Xanthohumol and Its Selected Structural Analogues. AB - The objective of this study was to evaluate the antimicrobial activity of structural analogues of xanthohumol 1, a flavonoid compound found in hops (Humulus lupulus). The agar-diffusion method using filter paper disks was applied. Biological tests performed for selected strains of Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria, fungi (Alternaria sp.), and yeasts (Rhodotorula rubra, Candida albicans) revealed that compounds with at least one hydroxyl group-all of them have it at the C-4 position-demonstrated good activity. Our research showed that the strain S. aureus was more sensitive to chalcones than to the isomers in which the heterocyclic ring C is closed (flavanones). The strain R. rubra was moderately sensitive to only one compound: 4-hydroxy-4'-methoxychalcone 8. Loss of the hydroxyl group in the B-ring of 4'-methoxychalcones or its replacement by a halogen atom (-Cl, -Br), nitro group (-NO2), ethoxy group (-OCH2CH3), or aliphatic substituent (-CH3, -CH2CH3) resulted in the loss of antimicrobial activity towards both R. rubra yeast and S. aureus bacteria. Xanthohumol 1, naringenin 5, and chalconaringenin 7 inhibited growth of S. aureus, whereas 4 hydroxy-4'-methoxychalcone 8 was active towards two strains: S. aureus and R. rubra. PMID- 27187330 TI - Identification of New Epididymal Luminal Fluid Proteins Involved in Sperm Maturation in Infertile Rats Treated by Dutasteride Using iTRAQ. AB - BACKGROUND: Spermatozoa become mature and acquire fertilizing capacity during their passage through the epididymal lumen. In this study, we identified new epididymal luminal fluid proteins involved in sperm maturation in infertile rats by dutasteride, a dual 5alpha-reductase inhibitor, in order to provide potential epididymal targets for new contraceptives and infertility treatment. METHODS: Male rats were treated with dutasteride for 28 consecutive days. We observed the protein expression profiles in the epididymal luminal fluids in infertile and normal rats using isobaric tags for relative and absolute quantitation (iTRAQ) technique. The confidence of proteome data was validated by enzyme-linked immunosorbent assays. RESULTS: 1045 proteins were tested, and 23 of them presented different expression profiling in the infertile and normal rats. The seven proteins were down-regulated, and 16 proteins were up-regulated. Among the seven proteins which were significantly down-regulated by dutasteride in the epididymal luminal fluids, there were three beta-defensins (Defb2, Defb18 and Defb39), which maybe the key proteins involved in epididymal sperm maturation and male fertility. CONCLUSIONS: We report for the first time that dutasteride influences the protein expression profiling in the epididymal luminal fluids of rats, and this result provides some new epididymal targets for male contraception and infertility therapy. PMID- 27187331 TI - Thermoregulated Coacervation, Metal-Encapsulation and Nanoparticle Synthesis in Novel Triazine Dendrimers. AB - The synthesis and solubility behaviors of four generation five (G5) triazine dendrimers are studied. While the underivatized cationic dendrimer is soluble in water, the acetylated and propanoylated derivatives undergo coacervation in water upon increasing temperature. Occurring around room temperature, this behavior is related to a liquid-liquid phase transition with a lower critical solution temperature (LCST) and is explained by differences in composition, notably, the hydrophobic nature of the terminal groups. Interestingly, the water solubility of the acetylated dendrimer is affected by the addition of selected metal ions. Titrating solutions of acetylated dendrimer at temperatures below the LCST with gold or palladium ions promoted precipitation, but platinum, iridium, and copper did not. Gold nanoparticles having diameters of 2.5 +/- 0.8 nm can be obtained from solutions of the acetylated dendrimer at concentrations of gold less than that required to induce precipitation by treating the solution with sodium borohydride. PMID- 27187332 TI - Effects of Brassicaceae Isothiocyanates on Prostate Cancer. AB - Despite the major progress made in the field of cancer biology, cancer is still one of the leading causes of mortality, and prostate cancer (PCa) is one of the most encountered malignancies among men. The effective management of this disease requires developing better anticancer agents with greater efficacy and fewer side effects. Nature is a large source for the development of chemotherapeutic agents, with more than 50% of current anticancer drugs being of natural origin. Isothiocyanates (ITCs) are degradation products from glucosinolates that are present in members of the family Brassicaceae. Although they are known for a variety of therapeutic effects, including antioxidant, immunostimulatory, anti inflammatory, antiviral and antibacterial properties, nowadays, cell line and animal studies have additionally indicated the chemopreventive action without causing toxic side effects of ITCs. In this way, they can induce cell cycle arrest, activate apoptosis pathways, increase the sensitivity of resistant PCa to available chemodrugs, modulate epigenetic changes and downregulate activated signaling pathways, resulting in the inhibition of cell proliferation, progression and invasion-metastasis. The present review summarizes the chemopreventive role of ITCs with a particular emphasis on specific molecular targets and epigenetic alterations in in vitro and in vivo cancer animal models. PMID- 27187333 TI - Quercetin and Its Anti-Allergic Immune Response. AB - Quercetin is the great representative of polyphenols, flavonoids subgroup, flavonols. Its main natural sources in foods are vegetables such as onions, the most studied quercetin containing foods, and broccoli; fruits (apples, berry crops, and grapes); some herbs; tea; and wine. Quercetin is known for its antioxidant activity in radical scavenging and anti-allergic properties characterized by stimulation of immune system, antiviral activity, inhibition of histamine release, decrease in pro-inflammatory cytokines, leukotrienes creation, and suppresses interleukin IL-4 production. It can improve the Th1/Th2 balance, and restrain antigen-specific IgE antibody formation. It is also effective in the inhibition of enzymes such as lipoxygenase, eosinophil and peroxidase and the suppression of inflammatory mediators. All mentioned mechanisms of action contribute to the anti-inflammatory and immunomodulating properties of quercetin that can be effectively utilized in treatment of late-phase, and late-late-phase bronchial asthma responses, allergic rhinitis and restricted peanut-induced anaphylactic reactions. Plant extract of quercetin is the main ingredient of many potential anti-allergic drugs, supplements and enriched products, which is more competent in inhibiting of IL-8 than cromolyn (anti-allergic drug disodium cromoglycate) and suppresses IL-6 and cytosolic calcium level increase. PMID- 27187334 TI - What Characteristics Confer Proteins the Ability to Induce Allergic Responses? IgE Epitope Mapping and Comparison of the Structure of Soybean 2S Albumins and Ara h 2. AB - Ara h 2, a peanut 2S albumin, is associated with severe allergic reactions, but a homologous protein, soybean 2S albumin, is not recognized as an important allergen. Structural difference between these proteins might explain this clinical discrepancy. Therefore, we mapped sequential epitopes and compared the structure of Ara h 2, Soy Al 1, and Soy Al 3 (Gly m 8) to confirm whether structural differences account for the discrepancy in clinical responses to these two proteins. Commercially synthesized peptides covering the full length of Ara h 2 and two soybean 2S albumins were analyzed by peptide microarray. Sera from 10 patients with peanut and soybean allergies and seven non-atopic controls were examined. The majority of epitopes in Ara h 2 identified by microarray are consistent with those identified previously. Several regions in the 2S albumins are weakly recognized by individual sera from different patients. A comparison of allergenic epitopes on peanut and soybean proteins suggests that loop-helix type secondary structures and some amino acids with a large side chain including lone electron pair, such as arginine, glutamine, and tyrosine, makes the peptides highly recognizable by the immune system. By utilizing the peptide microarray assay, we mapped IgE epitopes of Ara h 2 and two soybean 2S albumins. The use of peptide microarray mapping and analysis of the epitope characteristics may provide critical information to access the allergenicity of food proteins. PMID- 27187335 TI - Antifungal Activity of Eucalyptus Oil against Rice Blast Fungi and the Possible Mechanism of Gene Expression Pattern. AB - Eucalyptus oil possesses a wide spectrum of biological activity, including anti microbial, fungicidal, herbicidal, acaricidal and nematicidal properties. We studied anti-fungal activities of the leaf oil extracted from Eucalyptus. grandis * E. urophylla. Eleven plant pathogenic fungi were tested based on the mycelium growth rates with negative control. The results showed that Eucalyptus oil has broad-spectrum inhibitory effects toward these fungi. Remarkable morphological and structural alterations of hypha have been observed for Magnaporthe grisea after the treatment. The mRNA genome array of M. grisea was used to detect genes that were differentially expressed in the test strains treated by the Eucalyptus oil than the normal strains. The results showed 1919 genes were significantly affected, among which 1109 were down-regulated and 810 were up-regulated (p < 0.05, absolute fold change >2). According to gene ontology annotation analysis, these differentially expressed genes may cause abnormal structures and physiological function disorders, which may reduce the fungus growth. These results show the oil has potential for use in the biological control of plant disease as a green biopesticide. PMID- 27187337 TI - In Vivo Anti-Cancer Mechanism of Low-Molecular-Weight Fucosylated Chondroitin Sulfate (LFCS) from Sea Cucumber Cucumaria frondosa. AB - The low-molecular-weight fucosylated chondroitin sulfate (LFCS) was prepared from native fucosylated chondroitin sulfate (FCS), which was extracted and isolated from sea cucumber Cucumaria frondosa, and the anti-cancer mechanism of LFCS on mouse Lewis lung carcinoma (LLC) was investigated. The results showed that LFCS remarkably inhibited LLC growth and metastasis in a dose-dependent manner. LFCS induced cell cycle arrest by increasing p53/p21 expression and apoptosis through activation of caspase-3 activity in LLC cells. Meanwhile, LFCS suppressed the expression of vascular endothelial growth factor (VEGF), increased the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) and downregulated the matrix metalloproteinases (MMPs) level. Furthermore, LFCS significantly suppressed the activation of ERK1/2/p38 MAPK/NF-kappaB pathway, which played a prime role in expression of MMPs. All of these data indicate LFCS may be used as anti-cancer drug candidates and deserve further study. PMID- 27187338 TI - Adsorption of Emerging Ionizable Contaminants on Carbon Nanotubes: Advancements and Challenges. AB - The superior adsorption capacity of carbon nanotubes has been well recognized and there is a wealth of information in the literature concerning the adsorption of unionized organic pollutants on carbon nanotubes. Recently, the adsorption of emerging environmental pollutants, most of which are ionizable, has attracted increasing attention due to the heightened concerns about the accumulation of these emerging contaminants in the environment. These recent studies suggest that the adsorption of emerging ionizable contaminants on carbon nanotubes exhibit different characteristics than unionized ones. For example, a new charge-assisted intermolecular force has been proposed for ionizable compounds because some adsorption phenomenon cannot be easily explained by the conventional force theory. The adsorption of ionizable compounds also displayed much stronger dependence on solution pH and ionic strength than unionized compounds. This article aims to present a brief review on the current understanding of the adsorption of emerging ionizable contaminants to carbon nanotubes and discuss further research needs required to advance the mechanistic understanding of the interactions between ionizable contaminants and carbon nanotubes. PMID- 27187336 TI - Synthesis and in Vitro Antiproliferative Evaluation of C-13 Epimers of Triazolyl d-Secoestrone Alcohols: The First Potent 13alpha-d-Secoestrone Derivative. AB - The syntheses of C-13 epimeric 3-[(1-benzyl-1,2,3-triazol-4-yl)methoxy]-d secoestrones are reported. Triazoles were prepared from 3-(prop-2-inyloxy)-d secoalcohols and p-substituted benzyl azides via Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC). The antiproliferative activities of the products and their precursors were determined in vitro against a panel of human adherent cervical (HeLa, SiHa and C33A), breast (MCF-7, MDA-MB-231, MDA-MB-361 and T47D) and ovarian (A2780) cell lines by means of MTT assays. The orientation of the angular methyl group and the substitution pattern of the benzyl group of the azide greatly influenced the cell growth-inhibitory potential of the compounds. The 13beta derivatives generally proved to be more potent than their 13alpha counterparts. Introduction of a benzyltriazolylmethyl group onto the 3-OH position seemed to be advantageous. One 13alpha compound containing an unsubstituted benzyltriazolyl function displayed outstanding antiproliferative activities against three cell lines. PMID- 27187339 TI - Research on the Composition and Distribution of Organic Sulfur in Coal. AB - The structure and distribution of organic sulfur in coals of different rank and different sulfur content were studied by combining mild organic solvent extraction with XPS technology. The XPS results have shown that the distribution of organic sulfur in coal is related to the degree of metamorphism of coal. Namely, thiophenic sulfur content is reduced with decreasing metamorphic degree; sulfonic acid content rises with decreasing metamorphic degree; the contents of sulfate sulfur, sulfoxide and sulfone are rarely related with metamorphic degree. The solvent extraction and GC/MS test results have also shown that the composition and structure of free and soluble organic sulfur small molecules in coal is closely related to the metamorphic degree of coal. The free organic sulfur small molecules in coal of low metamorphic degree are mainly composed of aliphatic sulfides, while those in coal of medium and high metamorphic degree are mainly composed of thiophenes. Besides, the degree of aromatization of organic sulfur small molecules rises with increasing degree of coalification. PMID- 27187340 TI - Fusarium Toxins in Cereals: Occurrence, Legislation, Factors Promoting the Appearance and Their Management. AB - Fusarium diseases of small grain cereals and maize cause significant yield losses worldwide. Fusarium infections result in reduced grain yield and contamination with mycotoxins, some of which have a notable impact on human and animal health. Regulations on maximum limits have been established in various countries to protect consumers from the harmful effects of these mycotoxins. Several factors are involved in Fusarium disease and mycotoxin occurrence and among them environmental factors and the agronomic practices have been shown to deeply affect mycotoxin contamination in the field. In the present review particular emphasis will be placed on how environmental conditions and stress factors for the crops can affect Fusarium infection and mycotoxin production, with the aim to provide useful knowledge to develop strategies to prevent mycotoxin accumulation in cereals. PMID- 27187341 TI - The Mechanism by Which Amentoflavone Improves Insulin Resistance in HepG2 Cells. AB - BACKGROUND: The aim of this study was to explore the mechanism by which amentoflavone (AME) improves insulin resistance in a human hepatocellular liver carcinoma cell line (HepG2). METHODS: A model of insulin resistant cells was established in HepG2 by treatment with high glucose and insulin. The glucose oxidase method was used to detect the glucose consumption in each group. To determine the mechanism by which AME improves insulin resistance in HepG2 cells, enzyme-linked immunosorbent assay (ELISA) and western blotting were used to detect the expression of phosphatidyl inositol 3-kinase (PI3K), Akt, and pAkt; the activity of the enzymes involved in glucose metabolism; and the levels of inflammatory cytokines. RESULTS: Insulin resistance was successfully induced in HepG2 cells. After treatment with AME, the glucose consumption increased significantly in HepG2 cells compared with the model group (MG). The expression of PI3K, Akt, and pAkt and the activity of 6-phosphofructokinas (PFK-1), glucokinase (GCK), and pyruvate kinase (PK) increased, while the activity of glycogen synthase kinase-3 (GSK-3), phosphoenolpyruvate carboxylase kinase (PEPCK), and glucose-6-phosphatase (G-6-Pase) as well as the levels of interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF alpha), and C reactive protein (CRP) decreased. CONCLUSIONS: The mechanism by which treatment with AME improves insulin resistance in HepG2 cells may involve the PI3K-Akt signaling pathway, the processes of glucose oxygenolysis, glycogen synthesis, gluconeogenesis and inflammatory cytokine expression. PMID- 27187342 TI - Multivalent Carbohydrate-Lectin Interactions: How Synthetic Chemistry Enables Insights into Nanometric Recognition. AB - Glycan recognition by sugar receptors (lectins) is intimately involved in many aspects of cell physiology. However, the factors explaining the exquisite selectivity of their functional pairing are not yet fully understood. Studies toward this aim will also help appraise the potential for lectin-directed drug design. With the network of adhesion/growth-regulatory galectins as therapeutic targets, the strategy to recruit synthetic chemistry to systematically elucidate structure-activity relationships is outlined, from monovalent compounds to glyco clusters and glycodendrimers to biomimetic surfaces. The versatility of the synthetic procedures enables to take examining structural and spatial parameters, alone and in combination, to its limits, for example with the aim to produce inhibitors for distinct galectin(s) that exhibit minimal reactivity to other members of this group. Shaping spatial architectures similar to glycoconjugate aggregates, microdomains or vesicles provides attractive tools to disclose the often still hidden significance of nanometric aspects of the different modes of lectin design (sequence divergence at the lectin site, differences of spatial type of lectin-site presentation). Of note, testing the effectors alone or in combination simulating (patho)physiological conditions, is sure to bring about new insights into the cooperation between lectins and the regulation of their activity. PMID- 27187343 TI - Mechanism of the Zn(II)Phthalocyanines' Photochemical Reactions Depending on the Number of Substituents and Geometry. AB - In this work, the synthesis and the nonlinear absorption and population dynamics investigation of a series of zinc phthalocyanines (ZnPcs) dissolved in chloroform are reported. In order to determine the relevant spectroscopic parameters, such as absorption cross-sections of singlet and triplet excited states, fluorescence relaxation times, intersystem crossing, radiative decay and internal conversion, different optical and spectroscopic techniques were used. By single pulse and pulse train Z-scan techniques, respectively, singlet and triplet excited states' absorption cross-section were determined at 532 nm. Furthermore, the intersystem crossing time was obtained by using both techniques combined with the fluorescence lifetime determined by time-resolved fluorescence. The radiative and internal conversion rates were determined from the fluorescence quantum yield of the samples. Such spectroscopy parameters are fundamental for selecting photosensitizers used in photodynamic therapy, as well as for many other applications. PMID- 27187344 TI - Imidazolium Ionic Liquid Functionalized Carbon Nanotubes for Improved Interfacial Charge Transfer and Simultaneous Determination of Dihydroxybenzene Isomers. AB - In this paper; an imidazolium ionic liquid (IL) is used to functionalize multi walled carbon nanotubes (MWNTs) by covalent bonding on the MWNT surface. The functionalization not only provides a hydrophilic surface for ion accessibility but also prevents the aggregation of MWNTs. The IL-functionalized MWNTs were then applied for the electrochemical determination of the dihydroxybenzene isomers hydroquinone (HQ); catechol (CC); and resorcinol (RC), exhibiting excellent recognition ability towards the three compounds. The linear calibration ranges for HQ; CC and RC are 0.9-150 MUM; 0.9-150 MUM and 1.9-145 MUM and the detection limits are found to be 0.15 MUM for HQ; 0.10 MUM for CC and 0.38 MUM for RC based on S/N of 3. The proposed electrochemical sensor was also found to be useful for the determination of the dihydroxybenzene isomers in Yellow River water with reliable recovery. PMID- 27187345 TI - Characterization of the Principal Constituents of Danning Tablets, a Chinese Formula Consisting of Seven Herbs, by an UPLC-DAD-MS/MS Approach. AB - Danning Tablets are a traditional Chinese formula showing broad clinical applications in hepatobiliary diseases and containing a diversity of bioactive chemicals. However, the chemical profiling of the formula, which serves as the material foundation of its efficacy, is really a big challenge as Danning Tablets consist of seven herbs from different origins. An ultra-performance liquid chromatography coupled to diode array detection and electrospray ionization mass spectrometry (UPLC-DAD-ESI-MS/MS) approach was developed to characterize the principal polyphenol constituents in the formula. As a result, a total of 32 constituents, including 14 anthraquinones and their glucosides, four anthrones, two naphthalene glycosides, two stilbenes and 10 flavonoids were identified based on their retention time, UV absorption and MS/MS fragmentation patterns. The sources of these compounds were also illustrated. Most of the bioactive anthraquinone derivatives were found in Rhei Radix et Rhizoma or Polygoni Cuspidati Rhizoma et Radix, which are the Emperor drugs in the formula for its clinic usage. These findings indicate the merit of using this integrated UPLC-DAD ESI-MS/MS approach to rapidly illustrate the chemical foundation of complex formulas. The present study will facilitate the quality control of Danning Tablet formulas as well as the individual herbs. PMID- 27187347 TI - Recent Developments in Solid-Phase Extraction for Near and Attenuated Total Reflection Infrared Spectroscopic Analysis. AB - A review with more than 100 references on the principles and recent developments in the solid-phase extraction (SPE) prior and for in situ near and attenuated total reflection (ATR) infrared spectroscopic analysis is presented. New materials, chromatographic modalities, experimental setups and configurations are described. Their advantages for fast sample preparation for distinct classes of compounds containing different functional groups in order to enhance selectivity and sensitivity are discussed and compared. This is the first review highlighting both the fundamentals of SPE, near and ATR spectroscopy with a view to real sample applicability and routine analysis. Most of real sample analyses examples are found in environmental research, followed by food- and bioanalysis. In this contribution a comprehensive overview of the most potent SPE-NIR and SPE-ATR approaches is summarized and provided. PMID- 27187346 TI - Antitumor Effect of the Mannich Base(1,3-bis-((3-Hydroxynaphthalen-2 yl)phenylmethyl)urea) on Hepatocellular Carcinoma. AB - The present study was designed to evaluate the antitumor effects of the synthetic Mannich base 1,3-bis-((3-hydroxynaphthalen-2-yl)phenylmethyl)urea (1,3-BPMU) against HEP-G2 hepatoma cells and diethylnitrosamine (DEN)-induced hepatocarcinoma (HCC) in albino rats. In vitro analysis results revealed that 1,3 BPMU showed significant cytotoxicity and cell growth inhibition in HEP-G2 hepatoma cells in a concentration-dependent manner. Furthermore, flow cytometry results indicated that 1,3-BPMU enhanced early and late apoptosis. The maximum apoptosis was exhibited at a concentration of 100 MUg/mL of 1,3-BPMU. In in vivo analysis, DEN treatment increased the content of nucleic acids, LPO and the activities of AST, ALT, ALP, LDH, gammaGT and 5'NT with decreased antioxidant activity as compared to control rats. However, 1,3-BPMU treatment to DEN-induced rats decreased the content of nucleic acids, LPO and the activities of AST, ALT, ALP, LDH, gammaGT and 5'NT and increased the activities of SOD, CAT, GPx, GST and GR (p < 0.05). Furthermore, 1,3-BPMU enhanced the apoptosis via upregulation of caspase-3 and caspase-9 and the downregulation of Bcl-2 and Bcl-XL mRNA expression as compared to DEN-induced rats. Histological and ultrastructural investigation showed that 1,3-BPMU treatment renovated the internal architecture of the liver in DEN-induced rats. In this study, the molecular and pre-clinical results obtained by treatment of DEN-induced rats with 1,3-BPMU suggested that 1,3-BPMU might be considered as an antitumor compound in the future. PMID- 27187348 TI - Synthesis and Biological Evaluation of Benzochromenopyrimidinones as Cholinesterase Inhibitors and Potent Antioxidant, Non-Hepatotoxic Agents for Alzheimer's Disease. AB - We report herein the straightforward two-step synthesis and biological assessment of novel racemic benzochromenopyrimidinones as non-hepatotoxic, acetylcholinesterase inhibitors with antioxidative properties. Among them, compound 3Bb displayed a mixed-type inhibition of human acetylcholinesterase (IC50 = 1.28 +/- 0.03 MUM), good antioxidant activity, and also proved to be non hepatotoxic on human HepG2 cell line. PMID- 27187349 TI - The Suppression of Columnar pi-Stacking in 3-Adamantyl-1-phenyl-1,4 dihydrobenzo[e][1,2,4]triazin-4-yl. AB - 3-Adamantyl-1-phenyl-1,4-dihydrobenzo[e][1,2,4]triazin-4-yl (4) crystallizes as chains of radicals where the spin bearing benzotriazinyl moieties are isolated from each other. Magnetic susceptibility studies in the 5-300 K temperature region indicate that radical 4 demonstrates typical paramagnetic behavior stemming from non-interacting S = 1/2 spins. PMID- 27187350 TI - Broadband Two-Photon Absorption Characteristics of Highly Photostable Fluorenyl Dicyanoethylenylated [60]Fullerene Dyads. AB - We synthesized four C60-(light-harvesting antenna) dyads C60 (>CPAF-Cn) (n = 4, 9, 12, or 18) 1-Cn for the investigation of their broadband nonlinear absorption effect. Since we have previously demonstrated their high function as two-photon absorption (2PA) materials at 1000 nm, a different 2PA wavelength of 780 nm was applied in the study. The combined data taken at two different wavelength ranges substantiated the broadband characteristics of 1-Cn. We proposed that the observed broadband absorptions may be attributed by a partial pi-conjugation between the C60 > cage and CPAF-Cn moieties, via endinitrile tautomeric resonance, giving a resonance state with enhanced molecular conjugation. This transient state could increase its 2PA and excited-state absorption at 800 nm. In addition, a trend of concentration-dependent 2PA cross-section (sigma2 ) and excited-state absorption magnitude was detected showing a higher sigma value at a lower concentration that was correlated to increasing molecular separation with less aggregation for dyads C60(>CPAF-C18) and C60(>CPAF-C9), as better 2PA and excited-state absorbers. PMID- 27187351 TI - Chronic Heat Stress Induces Immune Response, Oxidative Stress Response, and Apoptosis of Finishing Pig Liver: A Proteomic Approach. AB - Heat stress (HS) negatively affects human health, animal welfare, and livestock production. We analyzed the hepatic proteomes of finishing pigs subjected to chronic heat stress (HS), thermal neutral (TN), and restricted feed intake conditions, identifying differences between direct and indirect (via reduced feed intake) HS. Twenty-four castrated male pigs were randomly allocated to three treatments for three weeks: (1) thermal neutral (TN) (22 degrees C) with ad libitum feeding; (2) chronic HS (30 degrees C) with ad libitum feeding; and (3) TN, pair-fed to HS intake (PF). Hepatic proteome analysis was conducted using two dimensional gel electrophoresis and mass spectrometry. Both HS and PF significantly reduced liver weight (p < 0.05). Forty-five hepatic proteins were differentially abundant when comparing HS with TN (37), PF with TN (29), and HS with PF (16). These proteins are involved in heat shock response and immune defense, oxidative stress response, cellular apoptosis, metabolism, signal transduction, and cytoskeleton. We also observed increased abundance of proteins and enzymes associated with heat shock response and immune defense, reduced the redox state, enhanced multiple antioxidant abilities, and increased apoptosis in HS liver. Heat-load, independent of reduced feed intake, induced an innate immune response, while food restriction caused stress and cellular apoptosis. Our results provide novel insights into the effects of chronic HS on liver. PMID- 27187352 TI - Exploratory Characterization of Phenolic Compounds with Demonstrated Anti Diabetic Activity in Guava Leaves at Different Oxidation States. AB - Psidium guajava L. is widely used like food and in folk medicine all around the world. Many studies have demonstrated that guava leaves have anti-hyperglycemic and anti-hyperlipidemic activities, among others, and that these activities belong mainly to phenolic compounds, although it is known that phenolic composition in guava tree varies throughout seasonal changes. Andalusia is one of the regions in Europe where guava is grown, thus, the aim of this work was to study the phenolic compounds present in Andalusian guava leaves at different oxidation states (low, medium, and high). The phenolic compounds in guava leaves were determined by HPLC-DAD-ESI-QTOF-MS. The results obtained by chromatographic analysis reported that guava leaves with low degree of oxidation had a higher content of flavonols, gallic, and ellagic derivatives compared to the other two guava leaf samples. Contrary, high oxidation state guava leaves reported the highest content of cyanidin-glucoside that was 2.6 and 15 times higher than guava leaves with medium and low oxidation state, respectively. The QTOF platform permitted the determination of several phenolic compounds with anti-diabetic properties and provided new information about guava leaf phenolic composition that could be useful for nutraceutical production. PMID- 27187353 TI - Involvement of CmWRKY10 in Drought Tolerance of Chrysanthemum through the ABA Signaling Pathway. AB - Drought is one of the important abiotic factors that adversely affects plant growth and production. The WRKY transcription factor plays a pivotal role in plant growth and development, as well as in the elevation of many abiotic stresses. Among three major groups of the WRKY family, the group IIe WRKY has been the least studied in floral crops. Here, we report functional aspects of group IIe WRKY member, i.e., CmWRKY10 in chrysanthemum involved in drought tolerance. The transactivation assay showed that CmWRKY10 had transcriptional activity in yeast cells and subcellular localization demonstrated that it was localized in nucleus. Our previous study showed that CmWRKY10 could be induced by drought in chrysanthemum. Moreover, the overexpression of CmWRKY10 in transgenic chrysanthemum plants improved tolerance to drought stress compared to wild-type (WT). High expression of DREB1A, DREB2A, CuZnSOD, NCED3A, and NCED3B transcripts in overexpressed plants provided strong evidence that drought tolerance mechanism was associated with abscisic acid (ABA) pathway. In addition, lower accumulation of reactive oxygen species (ROS) and higher enzymatic activity of peroxidase, superoxide dismutase and catalase in CmWRKY10 overexpressed lines than that of WT demonstrates its role in drought tolerance. Together, these findings reveal that CmWRKY10 works as a positive regulator in drought stress by regulating stress related genes. PMID- 27187354 TI - Hairpin RNA Targeting Multiple Viral Genes Confers Strong Resistance to Rice Black-Streaked Dwarf Virus. AB - Rice black-streaked dwarf virus (RBSDV) belongs to the genus Fijivirus in the family of Reoviridae and causes severe yield loss in rice-producing areas in Asia. RNA silencing, as a natural defence mechanism against plant viruses, has been successfully exploited for engineering virus resistance in plants, including rice. In this study, we generated transgenic rice lines harbouring a hairpin RNA (hpRNA) construct targeting four RBSDV genes, S1, S2, S6 and S10, encoding the RNA-dependent RNA polymerase, the putative core protein, the RNA silencing suppressor and the outer capsid protein, respectively. Both field nursery and artificial inoculation assays of three generations of the transgenic lines showed that they had strong resistance to RBSDV infection. The RBSDV resistance in the segregating transgenic populations correlated perfectly with the presence of the hpRNA transgene. Furthermore, the hpRNA transgene was expressed in the highly resistant transgenic lines, giving rise to abundant levels of 21-24 nt small interfering RNA (siRNA). By small RNA deep sequencing, the RBSDV-resistant transgenic lines detected siRNAs from all four viral gene sequences in the hpRNA transgene, indicating that the whole chimeric fusion sequence can be efficiently processed by Dicer into siRNAs. Taken together, our results suggest that long hpRNA targeting multiple viral genes can be used to generate stable and durable virus resistance in rice, as well as other plant species. PMID- 27187355 TI - Cell and Signal Components of the Microenvironment of Bone Metastasis Are Affected by Hypoxia. AB - Bone metastatic cells release bone microenvironment proteins, such as the matricellular protein SPARC (secreted protein acidic and rich in cysteine), and share a cell signaling typical of the bone metabolism controlled by Runx2. The megakaryocytes in the bone marrow engrafted by the metastases seem to be one of the principal microenvironment sources of the biological stimuli, implicated in the formation of an osteoblastic niche, and affecting metastasis phenotype and colonization. Educated platelets in the circulation might derive from megakaryocytes in bone metastasis. The evaluation of predictive markers in the circulating platelets might be useful for the stratification of patients for therapeutic purposes. The hypoxic environment in bone metastasis is one of the key regulators of the network of the biological soluble and structural components of the matrix. In bone metastatic cells under hypoxia, similar patterns of Runx2 and SPARC are observed, both showing downregulation. Conversely, hypoxia induces Endothelin 1, which upregulates SPARC, and these biological stimuli may be considered prognostic markers of bone metastasis in breast carcinoma patients. PMID- 27187356 TI - Rapid Diminution in the Level and Activity of DNA-Dependent Protein Kinase in Cancer Cells by a Reactive Nitro-Benzoxadiazole Compound. AB - The expression and activity of DNA-dependent protein kinase (DNA-PK) is related to DNA repair status in the response of cells to exogenous and endogenous factors. Recent studies indicate that Epidermal Growth Factor Receptor (EGFR) is involved in modulating DNA-PK. It has been shown that a compound 4-nitro-7-[(1 oxidopyridin-2-yl)sulfanyl]-2,1,3-benzoxadiazole (NSC), bearing a nitro benzoxadiazole (NBD) scaffold, enhances tyrosine phosphorylation of EGFR and triggers downstream signaling pathways. Here, we studied the behavior of DNA-PK and other DNA repair proteins in prostate cancer cells exposed to compound NSC. We showed that both the expression and activity of DNA-PKcs (catalytic subunit of DNA-PK) rapidly decreased upon exposure of cells to the compound. The decline in DNA-PKcs was associated with enhanced protein ubiquitination, indicating the activation of cellular proteasome. However, pretreatment of cells with thioglycerol abolished the action of compound NSC and restored the level of DNA PKcs. Moreover, the decreased level of DNA-PKcs was associated with the production of intracellular hydrogen peroxide by stable dimeric forms of Cu/Zn SOD1 induced by NSC. Our findings indicate that reactive oxygen species and electrophilic intermediates, generated and accumulated during the redox transformation of NBD compounds, are primarily responsible for the rapid modulation of DNA-PKcs functions in cancer cells. PMID- 27187357 TI - Design and Application of Antimicrobial Peptide Conjugates. AB - Antimicrobial peptides (AMPs) are an interesting class of antibiotics characterized by their unique antibiotic activity and lower propensity for developing resistance compared to common antibiotics. They belong to the class of membrane-active peptides and usually act selectively against bacteria, fungi and protozoans. AMPs, but also peptide conjugates containing AMPs, have come more and more into the focus of research during the last few years. Within this article, recent work on AMP conjugates is reviewed. Different aspects will be highlighted as a combination of AMPs with antibiotics or organometallic compounds aiming to increase antibacterial activity or target selectivity, conjugation with photosensitizers for improving photodynamic therapy (PDT) or the attachment to particles, to name only a few. Owing to the enormous resonance of antimicrobial conjugates in the literature so far, this research topic seems to be very attractive to different scientific fields, like medicine, biology, biochemistry or chemistry. PMID- 27187358 TI - The Growing Complexity of Cancer Cell Response to DNA-Damaging Agents: Caspase 3 Mediates Cell Death or Survival? AB - It is widely stated that wild-type p53 either mediates the activation of cell cycle checkpoints to facilitate DNA repair and promote cell survival, or orchestrates apoptotic cell death following exposure to cancer therapeutic agents. This reigning paradigm has been challenged by numerous discoveries with different human cell types, including solid tumor-derived cell lines. Thus, activation of the p53 signaling pathway by ionizing radiation and other DNA damaging agents hinders apoptosis and triggers growth arrest (e.g., through premature senescence) in some genetic backgrounds; such growth arrested cells remain viable, secrete growth-promoting factors, and give rise to progeny with stem cell-like properties. In addition, caspase 3, which is best known for its role in the execution phase of apoptosis, has been recently reported to facilitate (rather than suppress) DNA damage-induced genomic instability and carcinogenesis. This observation is consistent with an earlier report demonstrating that caspase 3 mediates secretion of the pro-survival factor prostaglandin E2, which in turn promotes enrichment of tumor repopulating cells. In this article, we review these and related discoveries and point out novel cancer therapeutic strategies. One of our objectives is to demonstrate the growing complexity of the DNA damage response beyond the conventional "repair and survive, or die" hypothesis. PMID- 27187359 TI - Expression and Function of miR-155 in Diseases of the Gastrointestinal Tract. AB - MicroRNAs (miRNAs) are a type of small noncoding RNA that can regulate the expression of target genes under physiological and pathophysiological conditions. miR-155 is a multifunctional miRNA with inflammation-related and oncogenic roles. In particular, the dysregulation of miR-155 has been strongly implicated in Helicobacter pylori-related gastric disease, inflammatory bowel disease, and colorectal cancer in addition to being involved in molecular changes of important targets and signaling pathways. This review focuses on the expression and function of miR-155 during inflammation and carcinogenesis and its potential use as an effective therapeutic target for certain gastrointestinal diseases. PMID- 27187361 TI - Mitochondria in Ageing and Diseases: The Super Trouper of the Cell. AB - The past decade has witnessed an explosion of knowledge regarding how mitochondrial dysfunction may translate into ageing and disease phenotypes, as well as how it is modulated by genetic and lifestyle factors.[...]. PMID- 27187360 TI - G Protein-Coupled Receptor Signaling in Stem Cells and Cancer. AB - G protein-coupled receptors (GPCRs) are a large superfamily of cell-surface signaling proteins that bind extracellular ligands and transduce signals into cells via heterotrimeric G proteins. GPCRs are highly tractable drug targets. Aberrant expression of GPCRs and G proteins has been observed in various cancers and their importance in cancer stem cells has begun to be appreciated. We have recently reported essential roles for G protein-coupled receptor 84 (GPR84) and G protein subunit Galphaq in the maintenance of cancer stem cells in acute myeloid leukemia. This review will discuss how GPCRs and G proteins regulate stem cells with a focus on cancer stem cells, as well as their implications for the development of novel targeted cancer therapies. PMID- 27187362 TI - Evidence for the Induction of Key Components of the NOTCH Signaling Pathway via Deltamethrin and Azamethiphos Treatment in the Sea Louse Caligus rogercresseyi. AB - The extensive use of organophosphates and pyrethroids in the aquaculture industry has negatively impacted parasite sensitivity to the delousing effects of these antiparasitics, especially among sea lice species. The NOTCH signaling pathway is a positive regulator of ABC transporter subfamily C expression and plays a key role in the generation and modulation of pesticide resistance. However, little is known about the molecular mechanisms behind pesticide resistance, partly due to the lack of genomic and molecular information on the processes involved in the resistance mechanism of sea lice. Next-generation sequencing technologies provide an opportunity for rapid and cost-effective generation of genome-scale data. The present study, through RNA-seq analysis, determined that the sea louse Caligus rogercresseyi (C. rogercresseyi) specifically responds to the delousing drugs azamethiphos and deltamethrin at the transcriptomic level by differentially activating mRNA of the NOTCH signaling pathway and of ABC genes. These results suggest that frequent antiparasitic application may increase the activity of inhibitory mRNA components, thereby promoting inhibitory NOTCH output and conditions for increased resistance to delousing drugs. Moreover, data analysis underscored that key functions of NOTCH/ABC components were regulated during distinct phases of the drug response, thus indicating resistance modifications in C. rogercresseyi resulting from the frequent use of organophosphates and pyrethroids. PMID- 27187363 TI - Case Characterization, Clinical Features and Risk Factors in Drug-Induced Liver Injury. AB - Idiosyncratic drug-induced liver injury (DILI) caused by xenobiotics (drugs, herbals and dietary supplements) presents with a range of both phenotypes and severity, from acute hepatitis indistinguishable of viral hepatitis to autoimmune syndromes, steatosis or rare chronic vascular syndromes, and from asymptomatic liver test abnormalities to acute liver failure. DILI pathogenesis is complex, depending on the interaction of drug physicochemical properties and host factors. The awareness of risk factors for DILI is arising from the analysis of large databases of DILI cases included in Registries and Consortia networks around the world. These networks are also enabling in-depth phenotyping with the identification of predictors for severe outcome, including acute liver failure and mortality/liver transplantation. Genome wide association studies taking advantage of these large cohorts have identified several alleles from the major histocompatibility complex system indicating a fundamental role of the adaptive immune system in DILI pathogenesis. Correct case definition and characterization is crucial for appropriate phenotyping, which in turn will strengthen sample collection for genotypic and future biomarkers studies. PMID- 27187364 TI - MicroRNA in United Airway Diseases. AB - The concept of united airway diseases (UAD) has received increasing attention in recent years. Sustained and increased inflammation is a common feature of UAD, which is inevitably accompanied with marked gene modification and tight gene regulation. However, gene regulation in the common inflammatory processes in UAD remains unclear. MicroRNA (miRNA), a novel regulator of gene expression, has been considered to be involved in many inflammatory diseases. Although there are an increasing number of studies of miRNAs in inflammatory upper and lower airway diseases, few miRNAs have been identified that directly link the upper and lower airways. In this article, therefore, we reviewed the relevant studies available in order to improve the understanding of the roles of miRNAs in the interaction and pathogenesis of UAD. PMID- 27187366 TI - Hepcidin-Induced Iron Deficiency Is Related to Transient Anemia and Hypoferremia in Kawasaki Disease Patients. AB - Kawasaki disease (KD) is a type of systemic vasculitis that primarily affects children under the age of five years old. For sufferers of KD, intravenous immunoglobulin (IVIG) has been found to successfully diminish the occurrence of coronary artery lesions. Anemia is commonly found in KD patients, and we have shown that in appropriately elevated hepcidin levels are related to decreased hemoglobin levels in these patients. In this study, we investigated the time period of anemia and iron metabolism during different stages of KD. A total of 100 patients with KD and 20 control subjects were enrolled in this study for red blood cell and hemoglobin analysis. Furthermore, plasma, urine hepcidin, and plasma IL-6 levels were evaluated using enzyme-linked immunosorbent assay in 20 KD patients and controls. Changes in hemoglobin, plasma iron levels, and total iron binding capacity (TIBC) were also measured in patients with KD. Hemoglobin, iron levels, and TIBC were lower (p < 0.001, p = 0.009, and p < 0.001, respectively) while plasma IL-6 and hepcidin levels (both p < 0.001) were higher in patients with KD than in the controls prior to IVIG administration. Moreover, plasma hepcidin levels were positively and significantly correlated with urine hepcidin levels (p < 0.001) prior to IVIG administration. After IVIG treatment, plasma hepcidin and hemoglobin levels significantly decreased (both p < 0.001). Of particular note was a subsequent gradual increase in hemoglobin levels during the three weeks after IVIG treatment; nevertheless, the hemoglobin levels stayed lower in KD patients than in the controls (p = 0.045). These findings provide a longitudinal study of hemoglobin changes and among the first evidence that hepcidin induces transient anemia and hypoferremia during KD's acute inflammatory phase. PMID- 27187367 TI - Is the Efficiency of RNA Silencing Evolutionarily Regulated? AB - Small interfering RNAs (siRNAs) and microRNAs (miRNAs) regulate gene expression in a sequence-specific manner. Genes with partial complementarity to siRNA/miRNA sequences in their 3'-untranslated regions (UTRs) are suppressed by a mechanism referred to as the siRNA off-target effect or miRNA-mediated RNA silencing. However, the determinants of such RNA silencing efficiency are poorly understood. Previously, I and co-workers reported that the efficiency of RNA silencing is strongly correlated with the thermodynamic stability of base pairing in the duplex formed within an siRNA/miRNA and between the seed region and its target mRNA. In this review, I first summarize our previous studies that identified the thermodynamic parameter to estimate the silencing efficiency using the calculated base pairing stability: siRNAs downregulate the expression of off-target genes depending on the stability of binding between the siRNA seed region (nucleotides 2-8) and off-target mRNAs, and miRNAs downregulate target mRNA expression depending on the stability of the duplex formed between the 5' terminus of the miRNA and its target mRNA. I further discuss the possibility that such thermodynamic features of silencing efficiency may have arisen during evolution with increasing body temperature in various organisms. PMID- 27187365 TI - Non-Alcoholic Fatty Liver Disease and Extra-Hepatic Cancers. AB - Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease but the second cause of death among NAFLD patients are attributed to malignancies at both gastrointestinal (liver, colon, esophagus, stomach, and pancreas) and extra-intestinal sites (kidney in men, and breast in women). Obesity and related metabolic abnormalities are associated with increased incidence or mortality for a number of cancers. NAFLD has an intertwined relationship with metabolic syndrome and significantly contributes to the risk of hepatocellular carcinoma (HCC), but recent evidence have fuelled concerns that NAFLD may be a new, and added, risk factor for extra-hepatic cancers, particularly in the gastrointestinal tract. In this review we critically appraise key studies on NAFLD-associated extra-hepatic cancers and speculate on how NAFLD may influence carcinogenesis at these sites. PMID- 27187368 TI - The Effect of Minimally Invasive Hematoma Aspiration on the JNK Signal Transduction Pathway after Experimental Intracerebral Hemorrhage in Rats. AB - OBJECTIVE: To explore the effect of minimally invasive hematoma aspiration (MIHA) on the c-Jun NH2-terminal kinase (JNK) signal transduction pathway after intracerebral hemorrhage (ICH). METHODS: In this experiment, 300 adult male Wistar rats were randomly and averagely divided into sham-operated group, ICH group and MIHA group. In each group, 60 rats were used in the detection of indexes in this experiment, while the other 40 rats were used to replace rats which reached the exclusion criteria (accidental death or operation failure). In ICH group and MIHA group, ICH was induced by injection of 70 uL of autologous arterial blood into rat brain, while only the rats in MIHA group were treated by MIHA 6 h after ICH. Rats in sham-operated group were injected nothing into brains, and they were not treated either, like rats in ICH group. In each group, six rats were randomly selected to observe their Bederson's scales persistently (6, 24, 48, 72, 96, 120 h after ICH). According to the time they were sacrificed, the remaining rats in each group were divided into 3 subgroups (24, 72, 120 h). The change of brain water content (BWC) was measured by the wet weight to dry weight ratio method. The morphology of neurons in cortex was observed by the hematoxylin-eosin (HE) staining. The expressions of phospho-c-Jun NH2-terminal kinase (pJNK) and JNK in peri-hematomal brain tissue were determined by the immunohistochemistry (IHC) and Western blotting (WB). RESULTS: At all time points, compared with the ICH groups, the expression of pJNK decreased obviously in MIHA groups (p < 0.05), while their Bederson's scales and BWC declined, and neuron injury in the cortex was relieved. The expression level of JNK was not altered at different groups. The data obtained by IHC and WB indicated a high level of consistency, which provided a certain dependability of the test results. CONCLUSION: The JNK signal transduction pathway could be activated after intracerebral hemorrhage, with the expressions of pJNK increasing. MIHA could relieve the histo-pathological damage of nerve cells, reducing brain edema and neurological deficits, and these neuroprotective effects might be associated with suppression of JNK signal transduction pathway. PMID- 27187369 TI - Hybrid Cells Derived from Human Breast Cancer Cells and Human Breast Epithelial Cells Exhibit Differential TLR4 and TLR9 Signaling. AB - TLRs are important receptors of cells of the innate immune system since they recognize various structurally conserved molecular patterns of different pathogens as well as endogenous ligands. In cancer, the role of TLRs is still controversial due to findings that both regression and progression of tumors could depend on TLR signaling. In the present study, M13SV1-EGFP-Neo human breast epithelial cells, MDA-MB-435-Hyg human breast cancer cells and two hybrids M13MDA435-1 and -3 were investigated for TLR4 and TLR9 expression and signaling. RT-PCR data revealed that LPS and CpG-ODN induced the expression of pro inflammatory cytokines, like IFN-beta, TNF-alpha, IL-1beta and IL-6 in hybrid cells, but not parental cells. Interestingly, validation of RT-PCR data by Western blot showed detectable protein levels solely after LPS stimulation, suggesting that regulatory mechanisms are also controlled by TLR signaling. Analysis of pAKT and pERK1/2 levels upon LPS and CpG-ODN stimulation revealed a differential phosphorylation pattern in all cells. Finally, the migratory behavior of the cells was investigated showing that both LPS and CpG-ODN potently blocked the locomotory activity of the hybrid cells in a dose-dependent manner. In summary, hybrid cells exhibit differential TLR4 and TLR9 signaling. PMID- 27187370 TI - Design of Acceptors with Suitable Frontier Molecular Orbitals to Match Donors via Substitutions on Perylene Diimide for Organic Solar Cells. AB - A series of perylene diimide (PDI) derivatives have been investigated at the CAM B3LYP/6-31G(d) and the TD-B3LYP/6-31+G(d,p) levels to design solar cell acceptors with high performance in areas such as suitable frontier molecular orbital (FMO) energies to match oligo(thienylenevinylene) derivatives and improved charge transfer properties. The calculated results reveal that the substituents slightly affect the distribution patterns of FMOs for PDI-BI. The electron withdrawing group substituents decrease the FMO energies of PDI-BI, and the electron donating group substituents slightly affect the FMO energies of PDI-BI. The di-electron withdrawing group substituents can tune the FMOs of PDI-BI to be more suitable for the oligo(thienylenevinylene) derivatives. The electron withdrawing group substituents result in red shifts of absorption spectra and electron donating group substituents result in blue shifts for PDI-BI. The -CN substituent can improve the electron transport properties of PDI-BI. The -CH3 group in different positions slightly affects the electron transport properties of PDI-BI. PMID- 27187372 TI - Gene-Silencing-Induced Changes in Carbohydrate Conformation in Relation to Bioenergy Value and Carbohydrate Subfractions in Modeled Plant (Medicago sativa) with Down-Regulation of HB12 and TT8 Transcription Factors. AB - Gene silencing with RNA interference (RNAi) technology may be capable of modifying internal structure at a molecular level. This structural modification could affect biofunctions in terms of biodegradation, biochemical metabolism, and bioactive compound availability. The objectives of this study were to (1) Detect gene silencing-induced changes in carbohydrate molecular structure in an alfalfa forage (Medicago sativa spp. sativa: alfalfa) with down-regulation of genes that encode transcription factors TT8 and HB12; (2) Determine gene silencing-induced changes in nutrient bioutilization and bioavailability in the alfalfa forage (Medicago sativa); and (3) Quantify the correlation between gene silencing induced molecular structure changes and the nutrient bioutilization and bioavailability in animals of ruminants. The experimental treatments included: T1 = Non-transgenic and no-gene silenced alfalfa forage (code "NT"); T2 = HB12-RNAi forage with HB12 gene down regulation (code "HB12"); T3 = TT8-RNAi forage with TT8 gene down regulation (code "TT8"). The HB12 and TT8 gene silencing-induced molecular structure changes were determined by non-invasive and non-destructive advanced molecular spectroscopy in a middle infrared radiation region that focused on structural, non-structural and total carbohydrate compounds. The nutrient bioutilization and bioavailability of the modified forage were determined using NRC-2001 system in terms of total digestive nutrient (TDN), truly digestible fiber (tdNDF), non-fiber carbohydrate (tdNDF), fatty acid (tdFA), crude protein (tdCP) and bioenergy profiles (digestible energy, metabolizable energy, net energy) for ruminants. The carbohydrate subfractions were evaluated using the updated CNCPS 6.0 system. The results showed that gene silencing significantly affected tdNFC (42.3 (NT) vs. 38.7 (HB12) vs. 37.4% Dry Matter (TT8); p = 0.016) and tdCP (20.8 (NT) vs. 19.4 (HB12) vs. 22.3% DM (TT8); p = 0.009). The gene-silencing also affected carbohydrate CA4 (7.4 (NT) vs. 4.2 (HB12) and 4.4% carbohydrate (CHO) (TT8), p = 0.063) and CB1 fractions (5.3 (NT) vs. 2.0 (HB12) and 2.6% CHO (TT8), p = 0.006). The correlation study showed that the structural CHO functional group peak area intensity at ca. 1315 cm(-1) was significantly correlated to the TDN1x (r = -0.83, p = 0.042) and the tdNFC (r = 0.83, p = 0.042), the structural CHO functional group height intensity at ca. 1370 cm(-1) was significantly correlated to the tdNDF (r = -0.87, p = 0.025). The A_Non-stCHO to A_StCHO ratio and A_Non-stCHO to A_CHO ratio were significantly correlated to the tdFA (r = 0.83-0.91, p < 0.05). As to carbohydrate fractions, both CA4 and CB1 correlated with carbohydrate spectral intensity of the H_1415 and the H_1315 (p = 0.039; p = 0.059, respectively), CB3 tended to correlate with the H_1150, H_1100 and H_1025 (p < 0.10). In conclusion, RNAi-mediated silencing of HB12 and TT8 modified not only inherent CHO molecular structure but also the biofunctions. The CHO molecular structure changes induced by RNAi gene silencing were associated with biofunctions in terms of the carbohydrate subfractions and nutrient digestion. PMID- 27187371 TI - Managing Pancreatic Adenocarcinoma: A Special Focus in MicroRNA Gene Therapy. AB - Pancreatic cancer is an aggressive disease and the fourth most lethal cancer in developed countries. Despite all progress in medicine and in understanding the molecular mechanisms of carcinogenesis, pancreatic cancer still has a poor prognosis, the median survival after diagnosis being around 3 to 6 months and the survival rate of 5 years being less than 4%. For pancreatic ductal adenocarcinoma (PDAC), which represents more than 90% of new pancreatic cancer cases, the prognosis is worse than for the other cancers with a patient mortality of approximately 99%. Therefore, there is a pressing need for developing new and efficient therapeutic strategies for pancreatic cancer. In this regard, microRNAs not only have been seen as potential diagnostic and prognostic molecular markers but also as promising therapeutic agents. In this context, this review provides an examination of the most frequently deregulated microRNAs (miRNAs) in PDAC and their putative molecular targets involved in the signaling pathways of pancreatic?carcinogenesis. Additionally, it is presented a summary of gene therapy clinical trials involving miRNAs and it is illustrated the therapeutic potential associated to these small non-coding RNAs, for PDAC treatment. The facts presented here constitute a strong evidence of the remarkable opportunity associated to the application of microRNA-based therapeutic strategies as a novel approach for cancer therapy. PMID- 27187373 TI - Site-Specific Integration of Exogenous Genes Using Genome Editing Technologies in Zebrafish. AB - The zebrafish (Danio rerio) is an ideal vertebrate model to investigate the developmental molecular mechanism of organogenesis and regeneration. Recent innovation in genome editing technologies, such as zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 (Cas9) system, have allowed researchers to generate diverse genomic modifications in whole animals and in cultured cells. The CRISPR/Cas9 and TALEN techniques frequently induce DNA double-strand breaks (DSBs) at the targeted gene, resulting in frameshift-mediated gene disruption. As a useful application of genome editing technology, several groups have recently reported efficient site-specific integration of exogenous genes into targeted genomic loci. In this review, we provide an overview of TALEN- and CRISPR/Cas9-mediated site-specific integration of exogenous genes in zebrafish. PMID- 27187374 TI - A Comparison of Fresh Frozen vs. Formalin-Fixed, Paraffin-Embedded Specimens of Canine Mammary Tumors via Branched-DNA Assay. AB - Mammary neoplasms are the tumors most affecting female dogs and women. Formalin fixed, paraffin-embedded (FFPE) tissues are an invaluable source of archived biological material. Fresh frozen (FF) tissue is considered ideal for gene expression analysis. However, strategies based on FFPE material offer several advantages. Branched-DNA assays permit a reliable and fast workflow when analyzing gene expression. The aim of this study was to assess the comparability of the branched-DNA assay when analyzing certain gene expression patterns between FF and FFPE samples in canine mammary tumors. RNA was isolated from 109 FFPE samples and from 93 FF samples of different canine mammary tissues. Sixteen (16) target genes (Tp53; Myc; HMGA1; Pik3ca; Mcl1; MAPK3; FOXO3; PTEN; GATA4; PFDN5; HMGB1; MAPK1; BRCA2; BRCA1; HMGA2; and Her2) were analyzed via branched-DNA assay (b-DNA). ACTB, GAPDH, and HPRT1 were used as data normalizers. Overall, the relative gene expression of the two different origins of samples showed an agreement of 63%. Still, care should be taken, as FFPE specimens showed lower expression of the analyzed targets when compared to FF samples. The fact that the gene expression in FFPE proved to be lower than in FF specimens is likely to have been caused by the effect of storage time. ACTB had the best performance as a data normalizer. PMID- 27187375 TI - The Use of 1alpha,25-Dihydroxyvitamin D3 as an Anticancer Agent. AB - The notion that vitamin D can influence the incidence of cancer arose from epidemiological studies. The major source of vitamin D in the organism is skin production upon exposure to ultra violet-B. The very first observation of an inverse correlation between exposure of individuals to the sun and the likelihood of cancer was reported as early as 1941. In 1980, Garland and Garland hypothesised, from findings from epidemiological studies of patients in the US with colon cancer, that vitamin D produced in response to sun exposure is protective against cancer as opposed to sunlight per se. Later studies revealed inverse correlations between sun exposure and the occurrence of prostate and breast cancers. These observations prompted laboratory investigation of whether or not vitamin D had an effect on cancer cells. Vitamin D is not active against cancer cells, but the most active metabolite 1alpha,25-dihydroxyvitamin D3 (1,25D) has profound biological effects. Here, we review the anticancer action of 1,25D, clinical trials of 1,25D to date and the prospects of the future therapeutic use of new and low calcaemic analogues. PMID- 27187376 TI - Nrf2 Expressions Correlate with WHO Grades in Gliomas and Meningiomas. AB - BACKGROUND: Nuclear factor erythroid 2-related factor 2 (NFE2L2, also known as Nrf2) is associated with cellular progression and chemotherapeutic resistance in some human cancers. We tested the relationship between Nrf2 expression and survival of patients with primary brain tumors (PBTs). METHODS: In order to realize Nrf2 protein expression in gliomas, Western blot analysis was performed in normal brain tissue and U87MG, LN229, GBM8401 and U118MG glioma cell lines protein lysates. Then, U87MG, LN229, and GBM8401 mRNA were applied to performed quantitative RT-PCR for detect Nrf2 gene expression in glioma cell lines. At last, immunohistochemical analysis was used to determine the expression of Nrf2 in samples from 178 PBTs and 10 non-neoplastic brain tissues. RESULTS: In these included in vitro studies, both Nrf2 protein and mRNA expression in all human glioma cell lines were higher than normal brain tissue. Similarly, on the viewpoint of immunohistochemistry, Nrf2 expression in gliomas were positively correlated with World Health Organization (WHO) grades. Additionally, compared with the expression of Nrf2 in non-neoplastic brain tissue, expression in meningiomas was of a stronger intensity and was present in a higher percentage of cells. Furthermore, scores were significantly higher in WHO grade II than in WHO grade I meningiomas. Finally, overall survival tended to be shorter in patients whose PBTs had higher expression of Nrf2, although the correlation was not statistically significant. CONCLUSIONS: Nrf2 overexpression positively correlated with WHO grade in gliomas and meningiomas. On the other hand, Nrf2 immunohistochemical stain could help pathologists to differentiate atypical meningiomas from benign tumors. Therefore, Nrf2 expression may be a useful biomarker to predict WHO grade and cellular behavior of PBTs. PMID- 27187377 TI - Pigment Epithelium-Derived Factor (PEDF) Protects Osteoblastic Cell Line from Glucocorticoid-Induced Apoptosis via PEDF-R. AB - Pigment epithelial-derived factor (PEDF) is known as a widely expressed multifunctional secreted glycoprotein whose biological actions are cell-type dependent. Recent studies demonstrated that PEDF displays cytoprotective activity in several cell types. However, it remains unknown whether PEDF is involved in glucocorticoid-induced osteoblast death. The aim of this study was to examine the role of PEDF in osteoblast survival in response to dexamethasone, an active glucocorticoid analogue, and explore the underlying mechanism. In the present study, dexamethasone (DEX) was used to induce MC3T3-E1 pre-osteoblast apoptosis. PEDF mRNA and protein levels and cell apoptosis were determined respectively. Then PEDF receptor (PEDF-R)- and lysophosphatidic acid (LPA)-related signal transductions were assessed. Here we show that DEX down-regulates PEDF expression, which contributes to osteoblast apoptosis. As a result, exogenous recombinant PEDF (rPEDF) inhibited DEX-induced cell apoptosis. We confirmed that PEDF-R was expressed on MC3T3-E1 pre-osteoblast membrane and could bind to PEDF which increased the level of LPA and activated the phosphorylation of Akt. Our results suggest that PEDF attenuated DEX-induced apoptosis in MC3T3-E1 pre osteoblasts through LPA-dependent Akt activation via PEDF-R. PMID- 27187378 TI - The Relationship between NALP3 and Autoinflammatory Syndromes. AB - The nucleotide-binding domain, leucine-rich repeat/pyrin domain-containing-3 (NALP3) inflammasome, which is required for synthesis of interleukin-1beta, has been implicated in the pathogenesis of several autoinflammatory syndromes. This review of the literature summarizes the interconnectedness of NALP3 inflammasome with some of these disorders. Familial Mediterranean fever results from a mutation in the Mediterranean fever (MEFV) gene, which encodes the pyrin protein. Previous study results suggest that pyrin suppresses caspase-1 activation, perhaps by competing for the adaptor protein, termed, pyrin domain of apoptosis/speck-like protein containing a caspase-recruitment domain (ACS) which therefore interferes with NALP3 inflammasome activation. The nucleotide-binding domain, leucine-rich repeat/pyrin domain-containing-3 (NALP3) inflammasome is constitutively activated in cryopyrin-associated periodic syndromes due to gain of-function mutations resulting from point mutations within the neuronal apoptosis inhibitor protein/class 2 transcription factor/heterokaryon incompatibility/telomerase-associated protein-1 (NACHT) domain of the NALP3 protein. Pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome is caused by mutations in the genes encoding proline-serine-threonine phosphatase interacting protein 1 (PSTPIP1). These PSTPIP1 mutants are thought to bind to pyrin causing an increase in the pyrin domain of apoptosis/speck-like protein containing a caspase-recruitment domain (ASC) pyroptosome assembly leading to procaspase-1 recruitment and therefore its activation. Hyperimmunoglublinemia D syndrome is caused by mevalonate kinase (MVK) deficiency, which may be affected by protein accumulation that leads to NALP3 inflammasome activation. Tumor necrosis factor receptor-associated periodic syndrome is associated with mutations in the tumor necrosis factor receptor superfamily, member 1A (TNFRSF1A) gene which decreases the level of soluble tumor necrosis factor receptor-1 (TNFR1) leading to neutralization of tumor necrosis factor (TNF)-alpha. In general, these autoinflammatory disorders have shown a clinical response to interleukin-1 (IL-1) antagonists, suggesting that the NALP3 inflammasome serves a critical role in their pathogenesis. PMID- 27187380 TI - Thrombin Receptor-Activating Protein (TRAP)-Activated Akt Is Involved in the Release of Phosphorylated-HSP27 (HSPB1) from Platelets in DM Patients. AB - It is generally known that heat shock protein 27 (HSP27) is phosphorylated through p38 mitogen-activated protein (MAP) kinase. We have previously reported that HSP27 is released from human platelets associated with collagen-induced phosphorylation. In the present study, we conducted an investigation into the effect of thrombin receptor-activating protein (TRAP) on the release of HSP27 in platelets in type 2 diabetes mellitus (DM) patients. The phosphorylated-HSP27 levels induced by TRAP were directly proportional to the aggregation of platelets. The levels of phosphorylated-HSP27 (Ser-78) were correlated with the levels of phosphorylated-p38 MAP kinase and phosphorylated-Akt in the platelets stimulated by 10 uM TRAP but not with those of phosphorylated-p44/p42 MAP kinase. The levels of HSP27 released from the TRAP (10 uM)-stimulated platelets were correlated with the levels of phosphorylated-HSP27 in the platelets. The released platelet-derived growth factor-AB (PDGF-AB) levels were in parallel with the HSP27 levels released from the platelets stimulated by 10 uM TRAP. Although the area under the curve (AUC) of small aggregates (9-25 um) induced by 10 uM TRAP showed no significant correlation with the released HSP27 levels, AUC of medium aggregates (25-50 um), large aggregates (50-70 um) and light transmittance were significantly correlated with the released HSP27 levels. TRAP-induced phosphorylation of HSP27 was truly suppressed by deguelin, an inhibitor of Akt, in the platelets from a healthy subject. These results strongly suggest that TRAP induced activation of Akt in addition to p38 MAP kinase positively regulates the release of phosphorylated-HSP27 from human platelets, which is closely related to the platelet hyper-aggregation in type 2 DM patients. PMID- 27187379 TI - Advances of Proteomic Sciences in Dentistry. AB - Applications of proteomics tools revolutionized various biomedical disciplines such as genetics, molecular biology, medicine, and dentistry. The aim of this review is to highlight the major milestones in proteomics in dentistry during the last fifteen years. Human oral cavity contains hard and soft tissues and various biofluids including saliva and crevicular fluid. Proteomics has brought revolution in dentistry by helping in the early diagnosis of various diseases identified by the detection of numerous biomarkers present in the oral fluids. This paper covers the role of proteomics tools for the analysis of oral tissues. In addition, dental materials proteomics and their future directions are discussed. PMID- 27187385 TI - Bootstrapping Security Policies for Wearable Apps Using Attributed Structural Graphs. AB - We address the problem of bootstrapping security and privacy policies for newly deployed apps in wireless body area networks (WBAN) composed of smartphones, sensors and other wearable devices. We introduce a framework to model such a WBAN as an undirected graph whose vertices correspond to devices, apps and app resources, while edges model structural relationships among them. This graph is then augmented with attributes capturing the features of each entity together with user-defined tags. We then adapt available graph-based similarity metrics to find the closest app to a new one to be deployed, with the aim of reusing, and possibly adapting, its security policy. We illustrate our approach through a detailed smartphone ecosystem case study. Our results suggest that the scheme can provide users with a reasonably good policy that is consistent with the user's security preferences implicitly captured by policies already in place. PMID- 27187383 TI - A Tumor-Specific Neo-Antigen Caused by a Frameshift Mutation in BAP1 Is a Potential Personalized Biomarker in Malignant Peritoneal Mesothelioma. AB - Malignant peritoneal mesothelioma (MPM) is an aggressive rare malignancy associated with asbestos exposure. A better understanding of the molecular pathogenesis of MPM will help develop a targeted therapy strategy. Oncogene targeted depth sequencing was performed on a tumor sample and paired peripheral blood DNA from a patient with malignant mesothelioma of the peritoneum. Four somatic base-substitutions in NOTCH2, NSD1, PDE4DIP, and ATP10B and 1 insert frameshift mutation in BAP1 were validated by the Sanger method at the transcriptional level. A 13-amino acids neo-peptide of the truncated Bap1 protein, which was produced as a result of this novel frameshift mutation, was predicted to be presented by this patient's HLA-B protein. The polyclonal antibody of the synthesized 13-mer neo-peptide was produced in rabbits. Western blotting results showed a good antibody-neoantigen specificity, and Immunohistochemistry (IHC) staining with the antibody of the neo-peptide clearly differentiated neoplastic cells from normal cells. A search of the Catalogue of Somatic Mutations in Cancer (COSMIC) database also revealed that 53.2% of mutations in BAP1 were frameshift indels with neo-peptide formation. An identified tumor-specific neo-antigen could be the potential molecular biomarker for personalized diagnosis to precisely subtype rare malignancies such as MPM. PMID- 27187384 TI - Effect of AQP9 Expression in Androgen-Independent Prostate Cancer Cell PC3. AB - It is known that aquaporin 9 (AQP9) in the prostate was strictly upregulated by androgen and may represent a novel therapeutic target for several cancers, but whether AQP9 plays a role in the regulation of androgen-independent prostate cancer still remains unclear. In the present study, AQP9 was determined in prostate cancer and adjacent cancer tissues; AQP9-siRNA was applied to silencing AQP9 in androgen-independent prostate cancer cell PC3 cell line. Western blot and flow cytometry analysis were employed to detect changes in related-function of control and AQP9-siRNA groups. The results showed that AQP9 is significantly induced in cancer tissues than that in adjacent cancer tissues. Moreover, knockdown of AQP9 in PC3 androgen-independent prostate cancer cell prostate cancer cells increased inhibition rates of proliferation. In addition, knockdown of AQP9 resulted in a significant decrease in the expression of the Bcl-2 and with a notable increase in the expression of Bax and cleaved caspase 3, indicated that AQP9 knockdown promoted apoptosis in prostate cancer cells. From wound healing assay and matrigel invasion, we suggested that AQP9 expression affects the motility and invasiveness of prostate cancer cells. Moreover, In order to explore the pathway may be involved in AQP9-mediated motility and invasion of prostate cancer cells, the phosphorylation of ERK1/2 was significant suppressed in AQP9 siRNA-transfected cells compared with that in control cells, suggesting that AQP9 is involved in the activation of the ERK pathway in androgen independent prostate cancer cells. PMID- 27187381 TI - Pathogenetic and Therapeutic Applications of Tumor Necrosis Factor-alpha (TNF alpha) in Major Depressive Disorder: A Systematic Review. AB - Major depressive disorder (MDD) is characterized by mood, vegetative, cognitive, and even psychotic symptoms and signs that can cause substantial impairments in quality of life and functioning. Up to now, the exact pathogenesis of MDD remains poorly understood. Recent research has begun to reveal that the pro-inflammatory cytokines, particularly, tumor necrosis factor-alpha (TNF-alpha), play an integral role in the pathophysiology of depressive disorders and the mechanism of antidepressant treatment. On the base of several observations: it is found that subsets of MDD patients have enhanced plasma levels TNF-alpha; antidepressant treatments had linked with the decline of TNF-alpha; central administration of TNF-alpha gives rise to sickness behavior which shares features with depression; and a blockade of it can ameliorate depressive symptomatology in animal models and clinical trials. In this review article, we focus on recent evidence linking TNF-alpha and MDD looking at data from animal and clinical studies, illustrating the pathophysiological role, susceptibility and its therapeutic application in depression. We conclude by discussing future directions for research, in particular the opportunities for the development of novel therapeutics that target TNF-alpha. This will be very important for designing preventative strategies and for the identification of new drug targets and preventative strategies. PMID- 27187386 TI - Modeling of a Single-Notch Microfiber Coupler for High-Sensitivity and Low Detection-Limit Refractive Index Sensing. AB - A highly sensitive refractive index sensor with low detection limit based on an asymmetric optical microfiber coupler is proposed. It is composed of a silica optical microfiber and an As2Se3 optical microfiber. Due to the asymmetry of the microfiber materials, a single-notch transmission spectrum is demonstrated by the large refractive index difference between the two optical microfibers. Compared with the symmetric coupler, the bandwidth of the asymmetric structure is over one order of magnitude narrower than that of the former. Therefore, the asymmetric optical microfiber coupler based sensor can reach over one order of magnitude smaller detection limit, which is defined as the minimal detectable refractive index change caused by the surrounding analyte. With the advantage of large evanescent field, the results also show that a sensitivity of up to 3212 nm per refractive index unit with a bandwidth of 12 nm is achieved with the asymmetric optical microfiber coupler. Furthermore, a maximum sensitivity of 4549 nm per refractive index unit can be reached while the radii of the silica optical microfiber and As2Se3 optical microfiber are 0.5 MUm and a 0.128 MUm, respectively. This sensor component may have important potential for low detection-limit physical and biochemical sensing applications. PMID- 27187387 TI - Spectrum and Image Texture Features Analysis for Early Blight Disease Detection on Eggplant Leaves. AB - This study investigated both spectrum and texture features for detecting early blight disease on eggplant leaves. Hyperspectral images for healthy and diseased samples were acquired covering the wavelengths from 380 to 1023 nm. Four gray images were identified according to the effective wavelengths (408, 535, 624 and 703 nm). Hyperspectral images were then converted into RGB, HSV and HLS images. Finally, eight texture features (mean, variance, homogeneity, contrast, dissimilarity, entropy, second moment and correlation) based on gray level co occurrence matrix (GLCM) were extracted from gray images, RGB, HSV and HLS images, respectively. The dependent variables for healthy and diseased samples were set as 0 and 1. K-Nearest Neighbor (KNN) and AdaBoost classification models were established for detecting healthy and infected samples. All models obtained good results with the classification rates (CRs) over 88.46% in the testing sets. The results demonstrated that spectrum and texture features were effective for early blight disease detection on eggplant leaves. PMID- 27187382 TI - Sirolimus and Everolimus Pathway: Reviewing Candidate Genes Influencing Their Intracellular Effects. AB - Sirolimus (SRL) and everolimus (EVR) are mammalian targets of rapamycin inhibitors (mTOR-I) largely employed in renal transplantation and oncology as immunosuppressive/antiproliferative agents. SRL was the first mTOR-I produced by the bacterium Streptomyces hygroscopicus and approved for several medical purposes. EVR, derived from SRL, contains a 2-hydroxy-ethyl chain in the 40th position that makes the drug more hydrophilic than SRL and increases oral bioavailability. Their main mechanism of action is the inhibition of the mTOR complex 1 and the regulation of factors involved in a several crucial cellular functions including: protein synthesis, regulation of angiogenesis, lipid biosynthesis, mitochondrial biogenesis and function, cell cycle, and autophagy. Most of the proteins/enzymes belonging to the aforementioned biological processes are encoded by numerous and tightly regulated genes. However, at the moment, the polygenic influence on SRL/EVR cellular effects is still not completely defined, and its comprehension represents a key challenge for researchers. Therefore, to obtain a complete picture of the cellular network connected to SRL/EVR, we decided to review major evidences available in the literature regarding the genetic influence on mTOR-I biology/pharmacology and to build, for the first time, a useful and specific "SRL/EVR genes-focused pathway", possibly employable as a starting point for future in-depth research projects. PMID- 27187388 TI - A Dual-Field Sensing Scheme for a Guidance System for the Blind. AB - An electronic guidance system is very helpful in improving blind people's perceptions in a local environment. In our previous work "Lin, Q.; Han, Y. A Context-Aware-Based Audio Guidance System for Blind People Using a Multimodal Profile Model. Sensors 2014, 14, 18670-18700", a context-aware guidance system using a combination of a laser scanner and a camera was proposed. By using a near field graphical model, the proposed system could interpret a near-field scene in very high resolution. In this paper, our work is extended by adding a far-field graphical model. The integration of the near-field and the far-field models constitutes a dual-field sensing scheme. In the near-field range, reliable inference of the ground and object status is obtained by fusing range data and image data using the near-field graphical model. In the far-field range, which only the camera can cover, the far-field graphical model is proposed to interpret far-field image data based on appearance and spatial prototypes built using the near-field interpreted data. The dual-field sensing scheme provides a solution for the guidance systems to optimise their scene interpretation capability using simple sensor configurations. Experiments under various local conditions were conducted to show the efficiency of the proposed scheme in improving blind people's perceptions in urban environments. PMID- 27187390 TI - Image Quality Analysis and Optical Performance Requirement for Micromirror-Based Lissajous Scanning Displays. AB - Micromirror-based scanning displays have been the focus of a variety of applications. Lissajous scanning displays have advantages in terms of power consumption; however, the image quality is not good enough. The main reason for this is the varying size and the contrast ratio of pixels at different positions of the image. In this paper, the Lissajous scanning trajectory is analyzed and a new method based on the diamond pixel is introduced to Lissajous displays. The optical performance of micromirrors is discussed. A display system demonstrator is built, and tests of resolution and contrast ratio are conducted. The test results show that the new Lissajous scanning method can be used in displays by using diamond pixels and image quality remains stable at different positions. PMID- 27187389 TI - Wearable Multi-Frequency and Multi-Segment Bioelectrical Impedance Spectroscopy for Unobtrusively Tracking Body Fluid Shifts during Physical Activity in Real Field Applications: A Preliminary Study. AB - Bioelectrical Impedance Spectroscopy (BIS) allows assessing the composition of body districts noninvasively and quickly, potentially providing important physiological/clinical information. However, neither portable commercial instruments nor more advanced wearable prototypes simultaneously satisfy the demanding needs of unobtrusively tracking body fluid shifts in different segments simultaneously, over a broad frequency range, for long periods and with high measurements rate. These needs are often required to evaluate exercise tests in sports or rehabilitation medicine, or to assess gravitational stresses in aerospace medicine. Therefore, the aim of this work is to present a new wearable prototype for monitoring multi-segment and multi-frequency BIS unobtrusively over long periods. Our prototype guarantees low weight, small size and low power consumption. An analog board with current-injecting and voltage-sensing electrodes across three body segments interfaces a digital board that generates square-wave current stimuli and computes impedance at 10 frequencies from 1 to 796 kHz. To evaluate the information derivable from our device, we monitored the BIS of three body segments in a volunteer before, during and after physical exercise and postural shift. We show that it can describe the dynamics of exercise-induced changes and the effect of a sit-to-stand maneuver in active and inactive muscular districts separately and simultaneously. PMID- 27187391 TI - Carrying Position Independent User Heading Estimation for Indoor Pedestrian Navigation with Smartphones. AB - This paper proposes a novel heading estimation approach for indoor pedestrian navigation using the built-in inertial sensors on a smartphone. Unlike previous approaches constraining the carrying position of a smartphone on the user's body, our approach gives the user a larger freedom by implementing automatic recognition of the device carrying position and subsequent selection of an optimal strategy for heading estimation. We firstly predetermine the motion state by a decision tree using an accelerometer and a barometer. Then, to enable accurate and computational lightweight carrying position recognition, we combine a position classifier with a novel position transition detection algorithm, which may also be used to avoid the confusion between position transition and user turn during pedestrian walking. For a device placed in the trouser pockets or held in a swinging hand, the heading estimation is achieved by deploying a principal component analysis (PCA)-based approach. For a device held in the hand or against the ear during a phone call, user heading is directly estimated by adding the yaw angle of the device to the related heading offset. Experimental results show that our approach can automatically detect carrying positions with high accuracy, and outperforms previous heading estimation approaches in terms of accuracy and applicability. PMID- 27187392 TI - Assessment of Aliasing Errors in Low-Degree Coefficients Inferred from GPS Data. AB - With sparse and uneven site distribution, Global Positioning System (GPS) data is just barely able to infer low-degree coefficients in the surface mass field. The unresolved higher-degree coefficients turn out to introduce aliasing errors into the estimates of low-degree coefficients. To reduce the aliasing errors, the optimal truncation degree should be employed. Using surface displacements simulated from loading models, we theoretically prove that the optimal truncation degree should be degree 6-7 for a GPS inversion and degree 20 for combing GPS and Ocean Bottom Pressure (OBP) with no additional regularization. The optimal truncation degree should be decreased to degree 4-5 for real GPS data. Additionally, we prove that a Scaled Sensitivity Matrix (SSM) approach can be used to quantify the aliasing errors due to any one or any combination of unresolved higher degrees, which is beneficial to identify the major error source from among all the unresolved higher degrees. Results show that the unresolved higher degrees lower than degree 20 are the major error source for global inversion. We also theoretically prove that the SSM approach can be used to mitigate the aliasing errors in a GPS inversion, if the neglected higher degrees are well known from other sources. PMID- 27187393 TI - Absolute Position Sensing Based on a Robust Differential Capacitive Sensor with a Grounded Shield Window. AB - A simple differential capacitive sensor is provided in this paper to measure the absolute positions of length measuring systems. By utilizing a shield window inside the differential capacitor, the measurement range and linearity range of the sensor can reach several millimeters. What is more interesting is that this differential capacitive sensor is only sensitive to one translational degree of freedom (DOF) movement, and immune to the vibration along the other two translational DOFs. In the experiment, we used a novel circuit based on an AC capacitance bridge to directly measure the differential capacitance value. The experimental result shows that this differential capacitive sensor has a sensitivity of 2 * 10(-4) pF/MUm with 0.08 MUm resolution. The measurement range of this differential capacitive sensor is 6 mm, and the linearity error are less than 0.01% over the whole absolute position measurement range. PMID- 27187395 TI - An in-Depth Survey of Visible Light Communication Based Positioning Systems. AB - While visible light communication (VLC) has become the candidate for the wireless technology of the 21st century due to its inherent advantages, VLC based positioning also has a great chance of becoming the standard approach to positioning. Within the last few years, many studies on VLC based positioning have been published, but there are not many survey works in this field. In this paper, an in-depth survey of VLC based positioning systems is provided. More than 100 papers ranging from pioneering papers to the state-of-the-art in the field were collected and classified based on the positioning algorithms, the types of receivers, and the multiplexing techniques. In addition, current issues and research trends in VLC based positioning are discussed. PMID- 27187394 TI - Model-Driven Approach for Body Area Network Application Development. AB - This paper introduces the sensor-networked IoT model as a prototype to support the design of Body Area Network (BAN) applications for healthcare. Using the model, we analyze the synergistic effect of the functional requirements (data collection from the human body and transferring it to the top level) and non functional requirements (trade-offs between energy-security-environmental factors, treated as Quality-of-Service (QoS)). We use feature models to represent the requirements at the earliest stage for the analysis and describe a model driven methodology to design the possible BAN applications. Firstly, we specify the requirements as the problem domain (PD) variability model for the BAN applications. Next, we introduce the generative technology (meta-programming as the solution domain (SD)) and the mapping procedure to map the PD feature-based variability model onto the SD feature model. Finally, we create an executable meta-specification that represents the BAN functionality to describe the variability of the problem domain though transformations. The meta-specification (along with the meta-language processor) is a software generator for multiple BAN oriented applications. We validate the methodology with experiments and a case study to generate a family of programs for the BAN sensor controllers. This enables to obtain the adequate measure of QoS efficiently through the interactive adjustment of the meta-parameter values and re-generation process for the concrete BAN application. PMID- 27187397 TI - Communication Range Dynamics and Performance Analysis for a Self-Adaptive Transmission Power Controller. AB - The deployment of the nodes in a Wireless Sensor and Actuator Network (WSAN) is typically restricted by the sensing and acting coverage. This implies that the locations of the nodes may be, and usually are, not optimal from the point of view of the radio communication. Additionally, when the transmission power is tuned for those locations, there are other unpredictable factors that can cause connectivity failures, like interferences, signal fading due to passing objects and, of course, radio irregularities. A control-based self-adaptive system is a typical solution to improve the energy consumption while keeping good connectivity. In this paper, we explore how the communication range for each node evolves along the iterations of an energy saving self-adaptive transmission power controller when using different parameter sets in an outdoor scenario, providing a WSAN that automatically adapts to surrounding changes keeping good connectivity. The results obtained in this paper show how the parameters with the best performance keep a k-connected network, where k is in the range of the desired node degree plus or minus a specified tolerance value. PMID- 27187396 TI - Self-Mixing Demodulation for Coherent Phase-Sensitive OTDR System. AB - Phase-sensitive optical time domain reflectometry (F-OTDR) attracts much attention due to its capability of telling the type and position of an intrusion simultaneously. In recent decades, coherent F-OTDR has been demonstrated to realize long-distance detection. For coherent F-OTDR, there are three typical demodulation schemes in the reported studies. However, they still cannot realize real-time monitoring to satisfy practical demands. A simple and effective demodulation method based on self-mixing has been put forward to demodulate the beat signal in coherent F-OTDR. It not only saves a local electrical oscillator and frequency locked loop, but also demodulates the beat signal without residual frequency. Several vibrations with different frequency were separately applied at the same location of a 42.5 km fiber. The spatial resolution of 10 m and frequency response range from 8 Hz to 980 Hz have been achieved. The precise location with signal-to-noise ratio of 21.4 dB and broadband measurement demonstrate the self-mixing scheme can demodulate the coherent F-OTDR signal effectively. PMID- 27187398 TI - Particle and Photon Detection: Counting and Energy Measurement. AB - Fundamental limits for photon counting and photon energy measurement are reviewed for CCD and CMOS imagers. The challenges to extend photon counting into the visible/nIR wavelengths and achieve energy measurement in the UV with specific read noise requirements are discussed. Pixel flicker and random telegraph noise sources are highlighted along with various methods used in reducing their contribution on the sensor's read noise floor. Practical requirements for quantum efficiency, charge collection efficiency, and charge transfer efficiency that interfere with photon counting performance are discussed. Lastly we will review current efforts in reducing flicker noise head-on, in hopes to drive read noise substantially below 1 carrier rms. PMID- 27187399 TI - Coupled Integration of CSAC, MIMU, and GNSS for Improved PNT Performance. AB - Positioning, navigation, and timing (PNT) is a strategic key technology widely used in military and civilian applications. Global navigation satellite systems (GNSS) are the most important PNT techniques. However, the vulnerability of GNSS threatens PNT service quality, and integrations with other information are necessary. A chip scale atomic clock (CSAC) provides high-precision frequency and high-accuracy time information in a short time. A micro inertial measurement unit (MIMU) provides a strap-down inertial navigation system (SINS) with rich navigation information, better real-time feed, anti-jamming, and error accumulation. This study explores the coupled integration of CSAC, MIMU, and GNSS to enhance PNT performance. The architecture of coupled integration is designed and degraded when any subsystem fails. A mathematical model for a precise time aiding navigation filter is derived rigorously. The CSAC aids positioning by weighted linear optimization when the visible satellite number is four or larger. By contrast, CSAC converts the GNSS observations to range measurements by "clock coasting" when the visible satellite number is less than four, thereby constraining the error divergence of micro inertial navigation and improving the availability of GNSS signals and the positioning accuracy of the integration. Field vehicle experiments, both in open-sky area and in a harsh environment, show that the integration can improve the positioning probability and accuracy. PMID- 27187400 TI - Mobile Laser Scanning Systems for Measuring the Clearance Gauge of Railways: State of Play, Testing and Outlook. AB - The paper contains a survey of mobile scanning systems for measuring the railway clearance gauge. The research was completed as part of the project carried out for the PKP (PKP Polish Railway Lines S.A., Warsaw, Poland) in 2011-2013. The authors conducted experiments, including a search for the latest solutions relating to mobile measurement systems that meet the basic requirement. At the very least, these solutions needed to be accurate and have the ability for quick retrieval of data. In the paper, specifications and the characteristics of the component devices of the scanning systems are described. Based on experiments, the authors did some examination of the selected mobile systems to be applied for measuring the clearance gauge. The Riegl (VMX-250) and Z+F (Zoller + Frohlich) Solution were tested. Additional test measurements were carried out within a 30 kilometer section of the Warsaw-Krakow route. These measurements were designed so as to provide various elements of the railway infrastructure, the track geometry and the installed geodetic control network. This ultimately made it possible to reduce the time for the preparation of geodetic reference measurements for the testing of the accuracy of the selected systems. Reference measurements included the use of the polar method to select profiles perpendicular to the axis of the track. In addition, the coordinates selected were well defined as measuring points of the objects of the infrastructure of the clearance gauge. All of the tested systems meet the accuracy requirements initially established (within the range of 2 cm as required by the PKP). The tested systems have shown their advantages and disadvantages. PMID- 27187401 TI - Wind Tunnel Analysis of the Airflow through Insect-Proof Screens and Comparison of Their Effect When Installed in a Mediterranean Greenhouse. AB - The present work studies the effect of three insect-proof screens with different geometrical and aerodynamic characteristics on the air velocity and temperature inside a Mediterranean multi-span greenhouse with three roof vents and without crops, divided into two independent sectors. First, the insect-proof screens were characterised geometrically by analysing digital images and testing in a low velocity wind tunnel. The wind tunnel tests gave screen discharge coefficient values of Cd,phi of 0.207 for screen 1 (10 * 20 threads.cm(-2); porosity phi = 35.0%), 0.151 for screen 2 (13 * 30 threads.cm(-2); phi = 26.3%) and 0.325 for screen 3 (10 * 20 threads.cm(-2); porosity phi = 36.0%), at an air velocity of 0.25 m.s(-1). Secondly, when screens were installed in the greenhouse, we observed a statistical proportionality between the discharge coefficient at the openings and the air velocity ui measured in the centre of the greenhouse, ui = 0.856 Cd + 0.062 (R2 = 0.68 and p-value = 0.012). The inside-outside temperature difference DeltaTio diminishes when the inside velocity increases following the statistically significant relationship DeltaTio = (-135.85 + 57.88/ui)(0.5) (R2 = 0.85 and p-value = 0.0011). Different thread diameters and tension affects the screen thickness, and means that similar porosities may well be associated with very different aerodynamic characteristics. Screens must be characterised by a theoretical function Cd,phi = [(2eMU/Kprho).(1/us) + (2eY/Kp(0.5))](-0.5) that relates the discharge coefficient of the screen Cd,phi with the air velocity us. This relationship depends on the three parameters that define the aerodynamic behaviour of porous medium: permeability Kp, inertial factor Y and screen thickness e (and on air temperature that determine its density rho and viscosity MU). However, for a determined temperature of air, the pressure drop-velocity relationship can be characterised only with two parameters: DeltaP = aus2 + bus. PMID- 27187402 TI - An Energy Saving System for a Beam Pumping Unit. AB - Beam pumping units are widely used in the oil production industry, but the energy efficiency of this artificial lift machinery is generally low, especially for the low-production well and high-production well in the later stage. There are a number of ways for energy savings in pumping units, with the periodic adjustment of stroke speed and rectification of balance deviation being two important methods. In the paper, an energy saving system for a beam pumping unit (ESS-BPU) based on the Internet of Things (IoT) was proposed. A total of four types of sensors, including load sensor, angle sensor, voltage sensor, and current sensor, were used to detect the operating conditions of the pumping unit. Data from these sensors was fed into a controller installed in an oilfield to adjust the stroke speed automatically and estimate the degree of balance in real-time. Additionally, remote supervision could be fulfilled using a browser on a computer or smartphone. Furthermore, the data from a practical application was recorded and analyzed, and it can be seen that ESS-BPU is helpful in reducing energy loss caused by unnecessarily high stroke speed and a poor degree of balance. PMID- 27187403 TI - Comprehensive Comparisons of Satellite Data, Signals, and Measurements between the BeiDou Navigation Satellite System and the Global Positioning System. AB - The Chinese BeiDou navigation satellite system (BDS) aims to provide global positioning service by 2020. The combined use of BDS and Global Positioning System (GPS) is proposed to provide navigation service with more stringent requirements. Actual satellite data, signals and measurements were collected for more than one month to analyze the positioning service qualities from both BDS and GPS. In addition to the conversions of coordinate and timing system, five data quality analysis (DQA) methods, three signal quality analysis (SQA) methods, and four measurement quality analysis (MQA) methods are proposed in this paper to improve the integrated positioning performance of BDS and GPS. As shown in the experiment results, issues related to BDS and GPS are resolved by the above proposed quality analysis methods. Thus, the anomalies in satellite data, signals and measurements can be detected by following the suggested resolutions to enhance the positioning performance of the combined use of BDS and GPS in the Asia Pacific region. PMID- 27187404 TI - Planar Position Sensor Based on Mono Sensing Electrode and Hybrid-Frequency Excitation. AB - A new way of measuring planar position for micrometric and sub-micrometric applications is presented with a mono sensing electrode and hybrid-frequency excitation. The sensing theory and operation principle are described and summarized, and a printed circuit board (PCB) sensor prototype is built and tested. It is shown by the experimental results that a very simple structure and geometric relationship are achieved. Meanwhile, displacement sensitivity on an order of 1.50 mV per micron and measurement repeatability better than 0.002 mm are easily fulfilled for a square zone of 256 mm2, making it a valuable alternative measurement device candidate for flexible and low-cost planar position detection. PMID- 27187405 TI - A Nonlinear Framework of Delayed Particle Smoothing Method for Vehicle Localization under Non-Gaussian Environment. AB - In this paper, a novel nonlinear framework of smoothing method, non-Gaussian delayed particle smoother (nGDPS), is proposed, which enables vehicle state estimation (VSE) with high accuracy taking into account the non-Gaussianity of the measurement and process noises. Within the proposed method, the multivariate Student's t-distribution is adopted in order to compute the probability distribution function (PDF) related to the process and measurement noises, which are assumed to be non-Gaussian distributed. A computation approach based on Ensemble Kalman Filter (EnKF) is designed to cope with the mean and the covariance matrix of the proposal non-Gaussian distribution. A delayed Gibbs sampling algorithm, which incorporates smoothing of the sampled trajectories over a fixed-delay, is proposed to deal with the sample degeneracy of particles. The performance is investigated based on the real-world data, which is collected by low-cost on-board vehicle sensors. The comparison study based on the real-world experiments and the statistical analysis demonstrates that the proposed nGDPS has significant improvement on the vehicle state accuracy and outperforms the existing filtering and smoothing methods. PMID- 27187406 TI - Current Developments on Optical Feedback Interferometry as an All-Optical Sensor for Biomedical Applications. AB - Optical feedback interferometry (OFI) sensors are experiencing a consistent increase in their applications to biosensing due to their contactless nature, low cost and compactness, features that fit very well with current biophotonics research and market trends. The present paper is a review of the work in progress at UPC-CD6 and LAAS-CNRS related to the application of OFI to different aspects of biosensing, both in vivo and ex vivo. This work is intended to present the variety of opportunities and potential applications related to OFI that are available in the field. The activities presented are divided into two main sensing strategies: The measurement of optical path changes and the monitoring of flows, which correspond to sensing strategies linked to the reconstruction of changes of amplitude from the interferometric signal, and to classical Doppler frequency measurements, respectively. For optical path change measurements, measurements of transient pulses, usual in biosensing, together with the measurement of large displacements applied to designing palliative care instrumentation for Parkinson disease are discussed. Regarding the Doppler-based approach, progress in flow-related signal processing and applications in real time monitoring of non-steady flows, human blood flow monitoring and OFI pressure myograph sensing will be presented. In all cases, experimental setups are discussed and results presented, showing the versatility of the technique. The described applications show the wide capabilities in biosensing of the OFI sensor, showing it as an enabler of low-cost, all-optical, high accuracy biomedical applications. PMID- 27187408 TI - Retrieving Land Surface Temperature from Hyperspectral Thermal Infrared Data Using a Multi-Channel Method. AB - Land Surface Temperature (LST) is a key parameter in climate systems. The methods for retrieving LST from hyperspectral thermal infrared data either require accurate atmospheric profile data or require thousands of continuous channels. We aim to retrieve LST for natural land surfaces from hyperspectral thermal infrared data using an adapted multi-channel method taking Land Surface Emissivity (LSE) properly into consideration. In the adapted method, LST can be retrieved by a linear function of 36 brightness temperatures at Top of Atmosphere (TOA) using channels where LSE has high values. We evaluated the adapted method using simulation data at nadir and satellite data near nadir. The Root Mean Square Error (RMSE) of the LST retrieved from the simulation data is 0.90 K. Compared with an LST product from the Spinning Enhanced Visible and Infrared Imager (SEVIRI) on Meteosat, the error in the LST retrieved from the Infared Atmospheric Sounding Interferometer (IASI) is approximately 1.6 K. The adapted method can be used for the near-real-time production of an LST product and to provide the physical method to simultaneously retrieve atmospheric profiles, LST, and LSE with a first-guess LST value. The limitations of the adapted method are that it requires the minimum LSE in the spectral interval of 800-950 cm(-1) larger than 0.95 and it has not been extended for off-nadir measurements. PMID- 27187407 TI - Determination of Ignitable Liquids in Fire Debris: Direct Analysis by Electronic Nose. AB - Arsonists usually use an accelerant in order to start or accelerate a fire. The most widely used analytical method to determine the presence of such accelerants consists of a pre-concentration step of the ignitable liquid residues followed by chromatographic analysis. A rapid analytical method based on headspace-mass spectrometry electronic nose (E-Nose) has been developed for the analysis of Ignitable Liquid Residues (ILRs). The working conditions for the E-Nose analytical procedure were optimized by studying different fire debris samples. The optimized experimental variables were related to headspace generation, specifically, incubation temperature and incubation time. The optimal conditions were 115 degrees C and 10 min for these two parameters. Chemometric tools such as hierarchical cluster analysis (HCA) and linear discriminant analysis (LDA) were applied to the MS data (45-200 m/z) to establish the most suitable spectroscopic signals for the discrimination of several ignitable liquids. The optimized method was applied to a set of fire debris samples. In order to simulate post-burn samples several ignitable liquids (gasoline, diesel, citronella, kerosene, paraffin) were used to ignite different substrates (wood, cotton, cork, paper and paperboard). A full discrimination was obtained on using discriminant analysis. This method reported here can be considered as a green technique for fire debris analyses. PMID- 27187409 TI - The Real-Valued Sparse Direction of Arrival (DOA) Estimation Based on the Khatri Rao Product. AB - There is a problem that complex operation which leads to a heavy calculation burden is required when the direction of arrival (DOA) of a sparse signal is estimated by using the array covariance matrix. The solution of the multiple measurement vectors (MMV) model is difficult. In this paper, a real-valued sparse DOA estimation algorithm based on the Khatri-Rao (KR) product called the L1-RVSKR is proposed. The proposed algorithm is based on the sparse representation of the array covariance matrix. The array covariance matrix is transformed to a real valued matrix via a unitary transformation so that a real-valued sparse model is achieved. The real-valued sparse model is vectorized for transforming to a single measurement vector (SMV) model, and a new virtual overcomplete dictionary is constructed according to the KR product's property. Finally, the sparse DOA estimation is solved by utilizing the idea of a sparse representation of array covariance vectors (SRACV). The simulation results demonstrate the superior performance and the low computational complexity of the proposed algorithm. PMID- 27187410 TI - Measurement of Moisture in Wood for Application in the Restoration of Old Buildings. AB - There are many historic buildings whose construction is based on timber frame walls. Most buildings built during the nineteenth and early twentieth centuries were based on timber frame walls with vertical support elements. These timber frame elements are affected by their moisture content and by the passage of time. If the interaction of the timber frame walls with hygrothermal fluctuations were known, the maintenance of these buildings could be improved significantly. To determine the moisture content of wood there are two types of meters on the market: on the one hand, capacitance meters which consist of two side ends and where the moisture content is measured locally between two peaks. On the other hand, there are meters based on the variation of electromagnetic transmittance of timber, which depends on the moisture of timber. The second ones are very expensive and difficult to handle. This work presents a new non-intrusive capacitive sensor that measures the global moisture content in a section of the timber frame walls and therefore its accuracy is similar to the accuracy that can be obtained with electromagnetic transmittance meters. Additionally, as it is a capacitive sensor, it is low cost and easy to operate. PMID- 27187411 TI - Erratum: Sutapun, B. et al. Development and Beam-Shape Analysis of an Integrated Fiber-Optic Confocal Probe for High-Precision Central Thickness Measurement of Small-Radius Lenses. Sensors, 2015, 15, 8512-8526. PMID- 27187413 TI - Extracting Objects for Aerial Manipulation on UAVs Using Low Cost Stereo Sensors. AB - Giving unmanned aerial vehicles (UAVs) the possibility to manipulate objects vastly extends the range of possible applications. This applies to rotary wing UAVs in particular, where their capability of hovering enables a suitable position for in-flight manipulation. Their manipulation skills must be suitable for primarily natural, partially known environments, where UAVs mostly operate. We have developed an on-board object extraction method that calculates information necessary for autonomous grasping of objects, without the need to provide the model of the object's shape. A local map of the work-zone is generated using depth information, where object candidates are extracted by detecting areas different to our floor model. Their image projections are then evaluated using support vector machine (SVM) classification to recognize specific objects or reject bad candidates. Our method builds a sparse cloud representation of each object and calculates the object's centroid and the dominant axis. This information is then passed to a grasping module. Our method works under the assumption that objects are static and not clustered, have visual features and the floor shape of the work-zone area is known. We used low cost cameras for creating depth information that cause noisy point clouds, but our method has proved robust enough to process this data and return accurate results. PMID- 27187412 TI - Influences of Probe's Morphology for Metal Ion Detection Based on Light Addressable Potentiometric Sensors. AB - The sensing mechanism of binding Hg(2+) into thymine-thymine (T-T) mismatched base pairs was introduced into a light-addressable potentiometric sensor (LAPS) with anti-Hg(2+) aptamer as the sensing units. Three kinds of T-rich single strand DNA (ssDNA) chains with different spacer lengths, from 0 to 12 -CH2 groups, were designed to investigate surface charge and morphological effects on the LAPS' output. First, by comparing the responding of LAPS modified with three kinds of ssDNA, it was found that the best performance for Hg(2+) sensing was exhibited by the probe without -CH2 groups. The detection limit of Hg(2+) ion was 1 ppt under the optimal condition. Second, the cooperative effects of surface charge and morphology on the output were observed by the controlled experiments. The two effects were the negative charge balanced by metal cations and the morphological changing caused by the formation of T-Hg(2+)-T structure. In conclusion, not only the influences of the aptamer probe's morphology and surface charge was investigated on the platform of LAPS, but also sensing Hg(2+) ions was achieved for the first time by the presented aptamer LAPS. PMID- 27187414 TI - Stability-Aware Geographic Routing in Energy Harvesting Wireless Sensor Networks. AB - A new generation of wireless sensor networks that harvest energy from environmental sources such as solar, vibration, and thermoelectric to power sensor nodes is emerging to solve the problem of energy limitation. Based on the photo-voltaic model, this research proposes a stability-aware geographic routing for reliable data transmissions in energy-harvesting wireless sensor networks (EH WSNs) to provide a reliable routes selection method and potentially achieve an unlimited network lifetime. Specifically, the influences of link quality, represented by the estimated packet reception rate, on network performance is investigated. Simulation results show that the proposed method outperforms an energy-harvesting-aware method in terms of energy consumption, the average number of hops, and the packet delivery ratio. PMID- 27187417 TI - Anti-Oxidative Activity of Mytiloxanthin, a Metabolite of Fucoxanthin in Shellfish and Tunicates. AB - Anti-oxidative activities of mytiloxanthin, a metabolite of fucoxanthin in shellfish and tunicates, were investigated. Mytiloxanthin showed almost the same activities for quenching singlet oxygen and the inhibition of lipid peroxidation as those of astaxanthin, which is a well-known singlet oxygen quencher. Furthermore, mytiloxanthin showed excellent scavenging activity for hydroxyl radicals and this activity was markedly higher than that of astaxanthin. PMID- 27187416 TI - Effect of Chitosan Properties on Immunoreactivity. AB - Chitosan is a widely investigated biopolymer in drug and gene delivery, tissue engineering and vaccine development. However, the immune response to chitosan is not clearly understood due to contradicting results in literature regarding its immunoreactivity. Thus, in this study, we analyzed effects of various biochemical properties, namely degree of deacetylation (DDA), viscosity/polymer length and endotoxin levels, on immune responses by antigen presenting cells (APCs). Chitosan solutions from various sources were treated with mouse and human APCs (macrophages and/or dendritic cells) and the amount of tumor necrosis factor alpha (TNF-alpha) released by the cells was used as an indicator of immunoreactivity. Our results indicate that only endotoxin content and not DDA or viscosity influenced chitosan-induced immune responses. Our data also indicate that low endotoxin chitosan (<0.01 EU/mg) ranging from 20 to 600 cP and 80% to 97% DDA is essentially inert. This study emphasizes the need for more complete characterization and purification of chitosan in preclinical studies in order for this valuable biomaterial to achieve widespread clinical application. PMID- 27187415 TI - Chemical Variations on the p53 Reactivation Theme. AB - Among the tumor suppressor genes, p53 is one of the most studied. It is widely regarded as the "guardian of the genome", playing a major role in carcinogenesis. In fact, direct inactivation of the TP53 gene occurs in more than 50% of malignancies, and in tumors that retain wild-type p53 status, its function is usually inactivated by overexpression of negative regulators (e.g., MDM2 and MDMX). Hence, restoring p53 function in cancer cells represents a valuable anticancer approach. In this review, we will present an updated overview of the most relevant small molecules developed to restore p53 function in cancer cells through inhibition of the p53-MDMs interaction, or direct targeting of wild-type p53 or mutated p53. In addition, optimization approaches used for the development of small molecules that have entered clinical trials will be presented. PMID- 27187418 TI - Effect of Experimental Parameters on Alginate/Chitosan Microparticles for BCG Encapsulation. AB - The aim of the present study was to develop novel Mycobacterium bovis bacille Calmette-Guerin (BCG)-loaded polymeric microparticles with optimized particle surface characteristics and biocompatibility, so that whole live attenuated bacteria could be further used for pre-exposure vaccination against Mycobacterium tuberculosis by the intranasal route. BCG was encapsulated in chitosan and alginate microparticles through three different polyionic complexation methods by high speed stirring. For comparison purposes, similar formulations were prepared with high shear homogenization and sonication. Additional optimization studies were conducted with polymers of different quality specifications in a wide range of pH values, and with three different cryoprotectors. Particle morphology, size distribution, encapsulation efficiency, surface charge, physicochemical properties and biocompatibility were assessed. Particles exhibited a micrometer size and a spherical morphology. Chitosan addition to BCG shifted the bacilli surface charge from negative zeta potential values to strongly positive ones. Chitosan of low molecular weight produced particle suspensions of lower size distribution and higher stability, allowing efficient BCG encapsulation and biocompatibility. Particle formulation consistency was improved when the availability of functional groups from alginate and chitosan was close to stoichiometric proportion. Thus, the herein described microparticulate system constitutes a promising strategy to deliver BCG vaccine by the intranasal route. PMID- 27187419 TI - cDNA and Gene Structure of MytiLec-1, A Bacteriostatic R-Type Lectin from the Mediterranean Mussel (Mytilus galloprovincialis). AB - MytiLec is an alpha-d-galactose-binding lectin with a unique primary structure isolated from the Mediterranean mussel (Mytilus galloprovincialis). The lectin adopts a beta-trefoil fold that is also found in the B-sub-unit of ricin and other ricin-type (R-type) lectins. We are introducing MytiLec(-1) and its two variants (MytiLec-2 and -3), which both possess an additional pore-forming aerolysin-like domain, as members of a novel multi-genic "mytilectin family" in bivalve mollusks. Based on the full length mRNA sequence (911 bps), it was possible to elucidate the coding sequence of MytiLec-1, which displays an extended open reading frame (ORF) at the 5' end of the sequence, confirmed both at the mRNA and at the genomic DNA sequence level. While this extension could potentially produce a polypeptide significantly longer than previously reported, this has not been confirmed yet at the protein level. MytiLec-1 was revealed to be encoded by a gene consisting of two exons and a single intron. The first exon comprised the 5'UTR and the initial ATG codon and it was possible to detect a putative promoter region immediately ahead of the transcription start site in the MytiLec-1 genomic locus. The remaining part of the MytiLec-1 coding sequence (including the three sub-domains, the 3'UTR and the poly-A signal) was included in the second exon. The bacteriostatic activity of MytiLec-1 was determined by the agglutination of both Gram-positive and Gram-negative bacteria, which was reversed by the co-presence of alpha-galactoside. Altogether, these data support the classification of MytiLec-1 as a member of the novel mytilectin family and suggest that this lectin may play an important role as a pattern recognition receptor in the innate immunity of mussels. PMID- 27187420 TI - Bacterial Long-Chain Polyunsaturated Fatty Acids: Their Biosynthetic Genes, Functions, and Practical Use. AB - The nutritional and pharmaceutical values of long-chain polyunsaturated fatty acids (LC-PUFAs) such as arachidonic, eicosapentaenoic and docosahexaenoic acids have been well recognized. These LC-PUFAs are physiologically important compounds in bacteria and eukaryotes. Although little is known about the biosynthetic mechanisms and functions of LC-PUFAs in bacteria compared to those in higher organisms, a combination of genetic, bioinformatic, and molecular biological approaches to LC-PUFA-producing bacteria and some eukaryotes have revealed the notably diverse organization of the pfa genes encoding a polyunsaturated fatty acid synthase complex (PUFA synthase), the LC-PUFA biosynthetic processes, and tertiary structures of the domains of this enzyme. In bacteria, LC-PUFAs appear to take part in specific functions facilitating individual membrane proteins rather than in the adjustment of the physical fluidity of the whole cell membrane. Very long chain polyunsaturated hydrocarbons (LC-HCs) such as hentriacontanonaene are considered to be closely related to LC-PUFAs in their biosynthesis and function. The possible role of LC-HCs in strictly anaerobic bacteria under aerobic and anaerobic environments and the evolutionary relationships of anaerobic and aerobic bacteria carrying pfa-like genes are also discussed. PMID- 27187421 TI - The Effect of the Molecular Architecture on the Antioxidant Properties of Chitosan Gallate. AB - To elucidate the structure-antioxidant activity relationships of chitosan gallate (CG), a series of CG derivatives with different degrees of substitution (DS's) and molecular weights (MWs) were synthesized from chitosan (CS) and gallic acid (GA) via a free radical graft reaction. A higher MW led to a lower DS of CG. The structures of CG were characterized by FT-IR and 1H NMR, and results showed that GA was mainly conjugated to the C-2 and C-6 positions of the CS chain. The antioxidant activity (the DPPH radical scavenging activity and reducing power) were enhanced with an increased DS and a decreased MW of CG. A correlation between antioxidant activities and the DS and MW of CG was also established. In addition, a suitable concentration (0~250 MUg/mL) of CG with different MWs (32.78~489.32 kDa) and DS's (0~92.89 mg.GAE/g CG) has no cytotoxicity. These results should provide a guideline to the application of CG derivatives in food or pharmacology industries. PMID- 27187422 TI - A Mouse Model for Studying Nutritional Programming: Effects of Early Life Exposure to Soy Isoflavones on Bone and Reproductive Health. AB - Over the past decade, our research group has characterized and used a mouse model to demonstrate that "nutritional programming" of bone development occurs when mice receive soy isoflavones (ISO) during the first days of life. Nutritional programming of bone development can be defined as the ability for diet during early life to set a trajectory for better or compromised bone health at adulthood. We have shown that CD-1 mice exposed to soy ISO during early neonatal life have higher bone mineral density (BMD) and greater trabecular inter connectivity in long bones and lumbar spine at young adulthood. These skeletal sites also withstand greater forces before fracture. Because the chemical structure of ISO resembles that of 17-beta-estradiol and can bind to estrogen receptors in reproductive tissues, it was prudent to expand analyses to include measures of reproductive health. This review highlights aspects of our studies in CD-1 mice to understand the early life programming effects of soy ISO on bone and reproductive health. Preclinical mouse models can provide useful data to help develop and guide the design of studies in human cohorts, which may, depending on findings and considerations of safety, lead to dietary interventions that optimize bone health. PMID- 27187423 TI - Migrant Sexual Health Help-Seeking and Experiences of Stigmatization and Discrimination in Perth, Western Australia: Exploring Barriers and Enablers. AB - Increasing HIV notifications amongst migrant and mobile populations to Australia is a significant public health issue. Generalizations about migrant health needs and delayed or deterred help-seeking behaviors can result from disregarding the variation between and within cultures including factors, such as drivers for migration and country of birth. This study explored barriers and enablers to accessing sexual health services, including experiences of stigma and discrimination, within a purposive sample of sub-Saharan African, Southeast Asian, and East Asian migrants. A qualitative design was employed using key informant interviews and focus group discussions. A total of 45 people with ages ranging from 18 to 50 years, participated in focus group discussions. Common barriers and enablers to help seeking behaviors were sociocultural and religious influence, financial constraints, and knowledge dissemination to reduce stigma. Additionally, common experiences of stigma and discrimination were related to employment and the social and self-isolation of people living with HIV. Overcoming barriers to accessing sexual health services, imparting sexual health knowledge, recognizing variations within cultures, and a reduction in stigma and discrimination will simultaneously accelerate help-seeking and result in better sexual health outcomes in migrant populations. PMID- 27187425 TI - Identifying Ethical Issues in Mental Health Research with Minors Adolescents: Results of a Delphi Study. AB - Research with minors, especially for preventive purposes, e.g., suicide prevention, investigating risk or self-destructive behaviors such as deviance, drug abuse, or suicidal behavior, is ethically sensitive. We present a Delphi study exploring the ethical implications of the needs formulated by researchers in an international pre-conference who would benefit from ethics support and guidance in conducting Mental Health Research with minors. The resulting List of Ethical Issues (LEI) was submitted to a 2-rounds Delphi process via the Internet, including 34 multidisciplinary experts. In the first round, the experts reviewed the LEI and completed a questionnaire. Results from this round were analyzed and grouped in nine categories comprising 40 items. In the second round, the experts had to agree/disagree with the needs expressed in the LEI leading to a final list of 25 ethical issues considered relevant for Mental Health Research with minors such as: confidentiality of the sensitive data, competence for consenting alone and risk of harm and stigma related to the methodology used in research. It was shown that studies like SEYLE (Saving and Empowering Young Lives in Europe) trigger among researchers wishes to obtain specific recommendations helping to comply with standards for good practice in conducting research with minors. PMID- 27187424 TI - Attitude, Acceptability and Knowledge of HPV Vaccination among Local University Students in Hong Kong. AB - The Human Papillomavirus (HPV) vaccine has the great potential to prevent HPV related infections for millions of women and men worldwide. However, the success of the vaccine is highly dependent on the vaccination rate. Factors influencing the attitudes of undergraduate students towards HPV vaccination should be studied. This is a cross-sectional survey that was conducted to estimate the HPV vaccination rate among undergraduate students in Hong Kong, and to identify the predictors of their attitude towards HPV vaccination. The results showed that the HPV vaccination rate was 13.3%. Factors related to knowledge of vaccination were the main predictors of the students' attitude towards vaccination (there were seven predictors, with B = 1.36 to 2.30; p < 0.05), followed by gender (B = 1.40; p < 0.05), acceptable maximum price (B = 0.35; p < 0.05), and willingness to receive the HPV vaccine if it can protect against cervical/anal cancer and genital warts (B = -1.90; p < 0.001). The regression model that was developed based on the predictors had a moderate effect size (adj-R2 = 0.33). To conclude, the HPV vaccination rate among undergraduate students in Hong Kong was low. They should be provided with more active education and activities to promote HPV vaccination to improve their knowledge on the subject. PMID- 27187426 TI - The Risk of Breast Cancer in Women Using Menopausal Hormone Replacement Therapy in Taiwan. AB - Menopausal hormone replacement therapy (HRT) increases the risk of breast cancer in Western countries; however, there are fewer reports from the Asian population, which has a lower incidence of breast cancer. A population-based retrospective cohort study was conducted by analyzing longitudinal National Health Insurance claim data of a 200,000-person national representative cohort. A total of 22,929 women aged >=45 years in 1997 without previous diagnosis of breast cancer were enrolled and stratified into two birth cohorts born before or after 1933. HRT prescriptions were traced in outpatient data files and incident breast cancer cases were identified from 1997 to 2004. The Cox proportional hazards model was used to analyze breast cancer hazard ratio (HR). HRT users were censored after they discontinued HRT. The results showed that women born during 1933-1952 had a twofold increased risk of breast cancer (HR = 2.10, 95% CI = 1.47-3.00) compared with women born before 1933, when adjusted for HRT use. When adjusted for the birth-cohort difference, HRT users had significantly increased breast cancer HR versus non-users after four years of use (adjusted HR = 1.48, 95% CI = 1.03 2.13); the HR further increased to 1.95 (95% CI = 1.34-2.84) after eight years of use. In conclusion, a longer duration of current HRT use was associated with a higher risk of breast cancer independent of the birth-cohort difference. PMID- 27187427 TI - Preliminary Assessment of Health Risks of Potentially Toxic Elements in Settled Dust over Beijing Urban Area. AB - To examine levels, health risks, sources, and spatial distributions of potentially toxic elements in settled dust over Beijing urban area, 62 samples were collected mostly from residential building outdoor surfaces, and their <63 MUm fractions were measured for 12 potentially toxic elements. The results show that V, Cr, Mn, Co, Ni, and Ba in dust are from predominantly natural sources, whereas Cu, Zn, As, Cd, Sb, and Pb mostly originate from anthropogenic sources. Exposure to these elements in dust has significant non-cancer risks to children but insignificant to adults. Cancer risks of Cr, Co, Ni, As, and Cd via inhalation and dermal contact are below the threshold of 10(-6)-10(-4) but As via dust ingestion shows a tolerable risk. The non-cancer risks to children are contributed mainly (75%) by As, Pb, and Sb, and dominantly (92%) via dust ingestion, with relatively higher risks mainly occurring in the eastern and northeastern Beijing urban areas. Although Cd, Zn, and Cu in dust are heavily affected by anthropogenic sources, their health risks are insignificant. Source appointments suggest that coal burning emissions, the dominant source of As, are likely the largest contributors to the health risk, and traffic-related and industrial emissions are also important because they contribute most of the Pb and Sb in dust. PMID- 27187429 TI - Analysis of Sampling Methodologies for Noise Pollution Assessment and the Impact on the Population. AB - Today, noise pollution is an increasing environmental stressor. Noise maps are recognised as the main tool for assessing and managing environmental noise, but their accuracy largely depends on the sampling method used. The sampling methods most commonly used by different researchers (grid, legislative road types and categorisation methods) were analysed and compared using the city of Talca (Chile) as a test case. The results show that the stratification of sound values in road categories has a significantly lower prediction error and a higher capacity for discrimination and prediction than in the legislative road types used by the Ministry of Transport and Telecommunications in Chile. Also, the use of one or another method implies significant differences in the assessment of population exposure to noise pollution. Thus, the selection of a suitable method for performing noise maps through measurements is essential to achieve an accurate assessment of the impact of noise pollution on the population. PMID- 27187428 TI - A Primrose Path? Moderating Effects of Age and Gender in the Association between Green Space and Mental Health. AB - This paper explored whether the association between green space and mental health is moderated by age and gender. Questionnaires on psychopathology and quality of life were filled out by 4924 individuals from the general Dutch population and regressed on greenness levels. Green space was associated with better mental health, but only in specific age and gender groups, and only in a 3 km, not a 1 km buffer. The moderating effects of age and gender may be explained by whether or not people have the opportunity to make use of their green living environment. PMID- 27187430 TI - A Combination of Geographically Weighted Regression, Particle Swarm Optimization and Support Vector Machine for Landslide Susceptibility Mapping: A Case Study at Wanzhou in the Three Gorges Area, China. AB - In this study, a novel coupling model for landslide susceptibility mapping is presented. In practice, environmental factors may have different impacts at a local scale in study areas. To provide better predictions, a geographically weighted regression (GWR) technique is firstly used in our method to segment study areas into a series of prediction regions with appropriate sizes. Meanwhile, a support vector machine (SVM) classifier is exploited in each prediction region for landslide susceptibility mapping. To further improve the prediction performance, the particle swarm optimization (PSO) algorithm is used in the prediction regions to obtain optimal parameters for the SVM classifier. To evaluate the prediction performance of our model, several SVM-based prediction models are utilized for comparison on a study area of the Wanzhou district in the Three Gorges Reservoir. Experimental results, based on three objective quantitative measures and visual qualitative evaluation, indicate that our model can achieve better prediction accuracies and is more effective for landslide susceptibility mapping. For instance, our model can achieve an overall prediction accuracy of 91.10%, which is 7.8%-19.1% higher than the traditional SVM-based models. In addition, the obtained landslide susceptibility map by our model can demonstrate an intensive correlation between the classified very high susceptibility zone and the previously investigated landslides. PMID- 27187432 TI - Factors Affecting Parent's Perception on Air Quality-From the Individual to the Community Level. AB - The perception of air quality significantly affects the acceptance of the public of the government's environmental policies. The aim of this research is to explore the relationship between the perception of the air quality of parents and scientific monitoring data and to analyze the factors that affect parents' perceptions. Scientific data of air quality were obtained from Wuhan's environmental condition reports. One thousand parents were investigated for their knowledge and perception of air quality. Scientific data show that the air quality of Wuhan follows an improving trend in general, while most participants believed that the air quality of Wuhan has deteriorated, which indicates a significant difference between public perception and reality. On the individual level, respondents with an age of 40 or above (40 or above: OR = 3.252; 95% CI: 1.170-9.040), a higher educational level (college and above: OR = 7.598; 95% CI: 2.244-25.732) or children with poor healthy conditions (poor: OR = 6.864; 95% CI: 2.212-21.302) have much more negative perception of air quality. On the community level, industrial facilities, vehicles and city construction have major effects on parents' perception of air quality. Our investigation provides baseline information for environmental policy researchers and makers regarding the public's perception and expectation of air quality and the benefits to the environmental policy completing and enforcing. PMID- 27187431 TI - Effects of Fine Particulate Matter (PM2.5) on Systemic Oxidative Stress and Cardiac Function in ApoE(-/-) Mice. AB - AIM: In this study, we aimed to explore the toxic mechanisms of cardiovascular injuries induced by ambient fine particulate matter (PM2.5) in atherosclerotic susceptible ApoE(-/-) mice. An acute toxicological animal experiment was designed with PM2.5 exposure once a day, every other day, for three days. METHODS: ApoE(-/ ) and C57BL/6 mice were randomly categorized into four groups, respectively (n = 6): one control group, three groups exposed to PM2.5 alone at low-, mid-, and high-dose (3, 10, or 30 mg/kg b.w.). Heart rate (HR) and electrocardiogram (ECG) were monitored before instillation of PM2.5 and 24 h after the last instillation, respectively. Cardiac function was monitored by echocardiography (Echo) after the last instillation. Biomarkers of systemic oxidative injuries (MDA, SOD), heart oxidative stress (MDA, SOD), and NAD(P)H oxidase subunits (p22phox, p47phox) mRNA and protein expression were analyzed in mice. The results showed that PM2.5 exposure could trigger the significant increase of MDA, and induce the decrease of heart rate variability (HRV), a marker of cardiac autonomic nervous system (ANS) function with a dose-response manner. Meanwhile, abnormal ECG types were monitored in mice after exposure to PM2.5. The expression of cytokines related with oxidative injuries, and mRNA and protein expression of NADPH, increased significantly in ApoE(-/-) mice in the high-dose group when compared with the dose-matched C57BL6 mice, but no significant difference was observed at Echo. In conclusion, PM2.5 exposure could cause oxidative and ANS injuries, and ApoE(-/-) mice displayed more severe oxidative effects induced by PM2.5. PMID- 27187433 TI - Prevention of Asbestos-Related Disease in Countries Currently Using Asbestos. AB - More than 40 years of evaluation have consistently confirmed the carcinogenicity of asbestos in all of its forms. This notwithstanding, according to recent figures, the annual world production of asbestos is approximatively 2,000,000 tons. Currently, about 90% of world asbestos comes from four countries: Russia, China, Brazil and Kazakhstan; and the wide use of asbestos worldwide represents a global threat. The purpose of this paper is to present a review of the asbestos health impact and to discuss the role of epidemiological investigations in countries where asbestos is still used. In these contexts, new, "local" studies can stimulate awareness of the size of the problem by public opinion and other stakeholders and provide important information on the circumstances of exposure, as well as local asbestos-related health impacts. This paper suggests an agenda for an international cooperation framework dedicated to foster a public health response to asbestos, including: new epidemiological studies for assessing the health impact of asbestos in specific contexts; socio-cultural and economic analyses for contributing to identifying stakeholders and to address both the local and global implications of asbestos diffusion; public awareness on the health and socio-economic impact of asbestos use and banning. PMID- 27187435 TI - Brazilian Green Propolis Improves Antioxidant Function in Patients with Type 2 Diabetes Mellitus. AB - Propolis contains a variety of bioactive components and possesses many biological properties. This study was designed to evaluate potential effects of Brazilian green propolis on glucose metabolism and antioxidant function in patients with type 2 diabetes mellitus (T2DM). In the 18-week randomized controlled study, enrolled patients with T2DM were randomly assigned to Brazilian green propolis group (900 mg/day) (n = 32) and control group (n = 33). At the end of the study, no significant difference was found in serum glucose, glycosylated hemoglobin, insulin, aldose reductase or adiponectin between the two groups. However, serum GSH and total polyphenols were significantly increased, and serum carbonyls and lactate dehydrogenase activity were significantly reduced in the Brazilian green propolis group. Serum TNF-alpha was significantly decreased, whereas serum IL 1beta and IL-6 were significantly increased in the Brazilian green propolis group. It is concluded that Brazilian green propolis is effective in improving antioxidant function in T2DM patients. PMID- 27187434 TI - Combined Effects of Prenatal Exposures to Environmental Chemicals on Birth Weight. AB - Prenatal chemical exposure has been frequently associated with reduced fetal growth by single pollutant regression models although inconsistent results have been obtained. Our study estimated the effects of exposure to single pollutants and mixtures on birth weight in 248 mother-child pairs. Arsenic, copper, lead, manganese and thallium were measured in cord blood, cadmium in maternal blood, methylmercury in maternal hair, and five organochlorines, two perfluorinated compounds and diethylhexyl phthalate metabolites in cord plasma. Daily exposure to particulate matter was modeled and averaged over the duration of gestation. In single pollutant models, arsenic was significantly associated with reduced birth weight. The effect estimate increased when including cadmium, and mono-(2-ethyl-5 carboxypentyl) phthalate (MECPP) co-exposure. Combining exposures by principal component analysis generated an exposure factor loaded by cadmium and arsenic that was associated with reduced birth weight. MECPP induced gender specific effects. In girls, the effect estimate was doubled with co-exposure of thallium, PFOS, lead, cadmium, manganese, and mercury, while in boys, the mixture of MECPP with cadmium showed the strongest association with birth weight. In conclusion, birth weight was consistently inversely associated with exposure to pollutant mixtures. Chemicals not showing significant associations at single pollutant level contributed to stronger effects when analyzed as mixtures. PMID- 27187436 TI - Fever and Pain Management in Childhood: Healthcare Providers' and Parents' Adherence to Current Recommendations. AB - In order to evaluate the adherence of healthcare providers and parents to the current recommendations concerning fever and pain management, randomized samples of 500 healthcare providers caring for children and 500 families were asked to complete an anonymous questionnaire. The 378 health care providers (HCPs) responding to the survey (75.6%) included 144 primary care pediatricians (38.1%), 98 hospital pediatricians (25.9%), 62 pediatric residents (16.4%), and 71 pediatric nurses (19.6%); the 464 responding parents (92.8%) included 175 whose youngest (or only) child was <=5 years old (37.7%), 175 whose youngest (or only) child was aged 6-10 years (37.7%), and 114 whose youngest (or only) child was aged 11-14 years (24.6%). There were gaps in the knowledge of both healthcare providers and parents. Global adherence to the guidelines was lower among the pediatric nurses than the other healthcare providers (odds ratio 0.875; 95% confidence interval 0.795-0.964). Among the parents, those of children aged 6-10 and 11-14 years old, those who were older, and those without a degree answered the questions correctly significantly less frequently than the others. These findings suggest that there is an urgent need to improve the dissemination of the current recommendations concerning fever and pain management among healthcare providers and parents in order to avoid mistaken and sometimes risky attitudes, common therapeutic errors, and the unnecessary overloading of emergency department resources. Pediatric nurses and parents with older children, those who are older, and those with a lower educational level should be the priority targets of educational programmes. PMID- 27187437 TI - Expelling Stress for Primary School Teachers: Self-Affirmation Increases Positive Emotions in Teaching and Emotion Reappraisal. AB - The aim of the present pilot study was to assess the effect of a brief work related self-affirming implementation intention (WS-AII) on the well-being of primary school teachers. Participants were randomly allocated to one of two conditions: one in which they were asked to create a WS-AII or one in which they were asked to create a control implementation intention (C-II). State anxiety was measured pre- and post-manipulation, self-efficacy at post-manipulation only, and emotions in teaching and emotion regulation at baseline and at a two-week follow up. There were statistically significant differences between the WS-AII condition and the control. Teachers who created work-related self-affirming implementation intentions reported an immediate reduction in state anxiety. Positive effects extended over the two-week period, with teachers in the WS-AII condition also reporting more positive emotions in teaching and the use of reappraisal emotion regulation strategies rather than emotion suppression. Results suggest that the integration of the WS-AII into existing organisational practice may be of benefit to the well-being of teachers and other highly stressed workers. PMID- 27187438 TI - Opportunities for Environmental Noise Mapping in Saudi Arabia: A Case of Traffic Noise Annoyance in an Urban Area in Jeddah City. AB - As the traffic and other environmental noise generating activities are growing in The Kingdom of Saudi Arabia (KSA), adverse health and other impacts are expected to develop. The management of such problem involves many actions, of which noise mapping has been proven to be a helpful approach. The objective of the current study was to test the adequacy of the available data in KSA municipalities for generating urban noise maps and to verify the applicability of available environmental noise mapping and noise annoyance models for KSA. Therefore, noise maps were produced for Al-Fayha District in Jeddah City, KSA using commercially available noise mapping software and applying the French national computation method "NMPB" for traffic noise. Most of the data required for traffic noise prediction and annoyance analysis were available, either in the Municipality GIS department or in other governmental authorities. The predicted noise levels during the three time periods, i.e., daytime, evening, and nighttime, were found higher than the maximum recommended levels established in KSA environmental noise standards. Annoyance analysis revealed that high percentages of the District inhabitants were highly annoyed, depending on the type of planning zone and period of interest. These results reflect the urgent need to consider environmental noise reduction in KSA national plans. The accuracy of the predicted noise levels and the availability of most of the necessary data should encourage further studies on the use of noise mapping as part of noise reduction plans. PMID- 27187439 TI - Nonylphenol Toxicity Evaluation and Discovery of Biomarkers in Rat Urine by a Metabolomics Strategy through HPLC-QTOF-MS. AB - Nonylphenol (NP) was quantified using liquid chromatography tandem mass spectrometry (LC-MS/MS) in the urine and plasma of rats treated with 0, 50, and 250 mg/kg/day of NP for four consecutive days. A urinary metabolomic strategy was originally implemented by high performance liquid chromatography time of flight mass spectrometry (HPLC-QTOF-MS) to explore the toxicological effects of NP and determine the overall alterations in the metabolite profiles so as to find potential biomarkers. It is essential to point out that from the observation, the metabolic data were clearly clustered and separated for the three groups. To further identify differentiated metabolites, multivariate analysis, including principal component analysis (PCA), orthogonal partial least-squares discriminant analysis (OPLS-DA), high-resolution MS/MS analysis, as well as searches of Metlin and Massbank databases, were conducted on a series of metabolites between the control and dose groups. Finally, five metabolites, including glycine, glycerophosphocholine, 5-hydroxytryptamine, malonaldehyde (showing an upward trend), and tryptophan (showing a downward trend), were identified as the potential urinary biomarkers of NP-induced toxicity. In order to validate the reliability of these potential biomarkers, an independent validation was performed by using the multiple reaction monitoring (MRM)-based targeted approach. The oxidative stress reflected by urinary 8-oxo-deoxyguanosine (8 oxodG) levels was elevated in individuals highly exposed to NP, supporting the hypothesis that mitochondrial dysfunction was a result of xenoestrogen accumulation. This study reveals a promising approach to find biomarkers to assist researchers in monitoring NP. PMID- 27187440 TI - Physiological and Molecular Response of Prorocentrum minimum to Tannic Acid: An Experimental Study to Evaluate the Feasibility of Using Tannic Acid in Controling the Red Tide in a Eutrophic Coastal Water. AB - Bioassay and gene expression experiments were conducted in order to evaluate the growth and physiology of Prorocentrum minimum isolated from a eutrophic coastal water in response to tannic acid. In the bioassay experiments, variations in abundance, chlorophyll (chl) a concentration, maximum fluorescence (in vivo Fm), and photosynthetic efficiency (Fv/Fm) were measured over the course of a seven day incubation. Moreover, stress-related gene expression in both the control and an experimental (2.5 ppm TA treatment) group was observed for 24 h and 48 h. The molecular markers used in this study were the heat shock proteins (Hsp70 and Hsp90) and cyclophilin (CYP). The findings show that P. minimum can thrive and grow at low concentrations (<2.5 ppm) of tannic acid, and, above this concentration, cells begin to slow down development. In addition, TA concentration of 10 ppm halted photosynthetic activity. At the molecular level, treatment with tannic acid increased the expression of Hsp70, Hsp90, and CYP, and heat shock proteins are more upregulated than the cyclophilin gene. Exposure to tannic acid increased the expression of stress factors over time (48 h) by 10- to 27-fold the expression level of the control group. These results suggest that tannic acid can be used to control harmful algal blooms such as those containing P. minimum in eutrophic coastal waters. PMID- 27187442 TI - Distinct Morphology of Human T-Cell Leukemia Virus Type 1-Like Particles. AB - The Gag polyprotein is the main retroviral structural protein and is essential for the assembly and release of virus particles. In this study, we have analyzed the morphology and Gag stoichiometry of human T-cell leukemia virus type 1 (HTLV 1)-like particles and authentic, mature HTLV-1 particles by using cryogenic transmission electron microscopy (cryo-TEM) and scanning transmission electron microscopy (STEM). HTLV-1-like particles mimicked the morphology of immature authentic HTLV-1 virions. Importantly, we have observed for the first time that the morphology of these virus-like particles (VLPs) has the unique local feature of a flat Gag lattice that does not follow the curvature of the viral membrane, resulting in an enlarged distance between the Gag lattice and the viral membrane. Other morphological features that have been previously observed with other retroviruses include: (1) a Gag lattice with multiple discontinuities; (2) membrane regions associated with the Gag lattice that exhibited a string of bead like densities at the inner leaflet; and (3) an arrangement of the Gag lattice resembling a railroad track. Measurement of the average size and mass of VLPs and authentic HTLV-1 particles suggested a consistent range of size and Gag copy numbers in these two groups of particles. The unique local flat Gag lattice morphological feature observed suggests that HTLV-1 Gag could be arranged in a lattice structure that is distinct from that of other retroviruses characterized to date. PMID- 27187441 TI - Epigenetic Effect of Environmental Factors on Autism Spectrum Disorders. AB - Both environmental factors and genetic factors are involved in the pathogenesis of autism spectrum disorders (ASDs). Epigenetics, an essential mechanism for gene regulation based on chemical modifications of DNA and histone proteins, is also involved in congenital ASDs. It was recently demonstrated that environmental factors, such as endocrine disrupting chemicals and mental stress in early life, can change epigenetic status and gene expression, and can cause ASDs. Moreover, environmentally induced epigenetic changes are not erased during gametogenesis and are transmitted to subsequent generations, leading to changes in behavior phenotypes. However, epigenetics has a reversible nature since it is based on the addition or removal of chemical residues, and thus the original epigenetic status may be restored. Indeed, several antidepressants and anticonvulsants used for mental disorders including ASDs restore the epigenetic state and gene expression. Therefore, further epigenetic understanding of ASDs is important for the development of new drugs that take advantages of epigenetic reversibility. PMID- 27187443 TI - Correspondence of Neutralizing Humoral Immunity and CD4 T Cell Responses in Long Recovered Sudan Virus Survivors. AB - Robust humoral and cellular immunity are critical for survival in humans during an ebolavirus infection. However, the interplay between these two arms of immunity is poorly understood. To address this, we examined residual immune responses in survivors of the Sudan virus (SUDV) outbreak in Gulu, Uganda (2000 2001). Cytokine and chemokine expression levels in SUDV stimulated whole blood cultures were assessed by multiplex ELISA and flow cytometry. Antibody and corresponding neutralization titers were also determined. Flow cytometry and multiplex ELISA results demonstrated significantly higher levels of cytokine and chemokine responses in survivors with serological neutralizing activity. This correspondence was not detected in survivors with serum reactivity to SUDV but without neutralization activity. This previously undefined relationship between memory CD4 T cell responses and serological neutralizing capacity in SUDV survivors is key for understanding long lasting immunity in survivors of filovirus infections. PMID- 27187444 TI - Protein 2B of Coxsackievirus B3 Induces Autophagy Relying on Its Transmembrane Hydrophobic Sequences. AB - Coxsackievirus B (CVB) belongs to Enterovirus genus within the Picornaviridae family, and it is one of the most common causative pathogens of viral myocarditis in young adults. The pathogenesis of myocarditis caused by CVB has not been completely elucidated. In CVB infection, autophagy is manipulated to facilitate viral replication. Here we report that protein 2B, one of the non-structural proteins of CVB3, possesses autophagy-inducing capability. The autophagy-inducing motif of protein 2B was identified by the generation of truncated 2B and site directed mutagenesis. The expression of 2B alone was sufficient to induce the formation of autophagosomes in HeLa cells, while truncated 2B containing the two hydrophobic regions of the protein also induced autophagy. In addition, we demonstrated that a single amino acid substitution (56V->A) in the stem loop in between the two hydrophobic regions of protein 2B abolished the formation of autophagosomes. Moreover, we found that 2B and truncated 2B with autophagy inducting capability were co-localized with LC3-II. This study indicates that protein 2B relies on its transmembrane hydrophobic regions to induce the formation of autophagosomes, while 56 valine residue in the stem loop of protein 2B might exert critical structural influence on its two hydrophobic regions. These results may provide new insight for understanding the molecular mechanism of autophagy triggered by CVB infection. PMID- 27187446 TI - Making Bunyaviruses Talk: Interrogation Tactics to Identify Host Factors Required for Infection. AB - The identification of host cellular genes that act as either proviral or antiviral factors has been aided by the development of an increasingly large number of high-throughput screening approaches. Here, we review recent advances in which these new technologies have been used to interrogate host genes for the ability to impact bunyavirus infection, both in terms of technical advances as well as a summary of biological insights gained from these studies. PMID- 27187445 TI - Respiratory Syncytial Virus and Cellular Stress Responses: Impact on Replication and Physiopathology. AB - Human respiratory syncytial virus (RSV), a member of the Paramyxoviridae family, is a major cause of severe acute lower respiratory tract infection in infants, elderly and immunocompromised adults. Despite decades of research, a complete integrated picture of RSV-host interaction is still missing. Several cellular responses to stress are involved in the host-response to many virus infections. The endoplasmic reticulum stress induced by altered endoplasmic reticulum (ER) function leads to activation of the unfolded-protein response (UPR) to restore homeostasis. Formation of cytoplasmic stress granules containing translationally stalled mRNAs is a means to control protein translation. Production of reactive oxygen species is balanced by an antioxidant response to prevent oxidative stress and the resulting damages. In recent years, ongoing research has started to unveil specific regulatory interactions of RSV with these host cellular stress responses. Here, we discuss the latest findings regarding the mechanisms evolved by RSV to induce, subvert or manipulate the ER stress, the stress granule and oxidative stress responses. We summarize the evidence linking these stress responses with the regulation of RSV replication and the associated pathogenesis. PMID- 27187447 TI - A Mixed Flavonoid-Fish Oil Supplement Induces Immune-Enhancing and Anti Inflammatory Transcriptomic Changes in Adult Obese and Overweight Women-A Randomized Controlled Trial. AB - Flavonoids and fish oils have anti-inflammatory and immune-modulating influences. The purpose of this study was to determine if a mixed flavonoid-fish oil supplement (Q-Mix; 1000 mg quercetin, 400 mg isoquercetin, 120 mg epigallocatechin (EGCG) from green tea extract, 400 mg n3-PUFAs (omega-3 polyunsaturated fatty acid) (220 mg eicosapentaenoic acid (EPA) and 180 mg docosahexaenoic acid (DHA)) from fish oil, 1000 mg vitamin C, 40 mg niacinamide, and 800 ug folic acid) would reduce complications associated with obesity; that is, reduce inflammatory and oxidative stress markers and alter genomic profiles in overweight women. Overweight and obese women (n = 48; age = 40-70 years) were assigned to Q-Mix or placebo groups using randomized double-blinded placebo controlled procedures. Overnight fasted blood samples were collected at 0 and 10 weeks and analyzed for cytokines, C-reactive protein (CRP), F2-isoprostanes, and whole-blood-derived mRNA, which was assessed using Affymetrix HuGene-1_1 ST arrays. Statistical analysis included two-way ANOVA models for blood analytes and gene expression and pathway and network enrichment methods for gene expression. Plasma levels increased with Q-Mix supplementation by 388% for quercetin, 95% for EPA, 18% for DHA, and 20% for docosapentaenoic acid (DPA). Q-Mix did not alter plasma levels for CRP (p = 0.268), F2-isoprostanes (p = 0.273), and cytokines (p > 0.05). Gene set enrichment analysis revealed upregulation of pathways in Q-Mix vs. placebo related to interferon-induced antiviral mechanism (false discovery rate, FDR < 0.001). Overrepresentation analysis further disclosed an inhibition of phagocytosis-related inflammatory pathways in Q-Mix vs. placebo. Thus, a 10 week Q-Mix supplementation elicited a significant rise in plasma quercetin, EPA, DHA, and DPA, as well as stimulated an antiviral and inflammation whole-blood transcriptomic response in overweight women. PMID- 27187448 TI - Resveratrol Interferes with IL1-beta-Induced Pro-Inflammatory Paracrine Interaction between Primary Chondrocytes and Macrophages. AB - State of the art. Osteoarthritis (OA) is a chronic articular disease characterized by cartilage degradation and osteophyte formation. OA physiopathology is multifactorial and involves mechanical and hereditary factors. So far, there is neither preventive medicine to delay cartilage breakdown nor curative treatment. Objectives. To investigate pro-inflammatory paracrine interactions between human primary chondrocytes and macrophages following interleukin-1-beta (IL-1beta) treatment; to evaluate the molecular mechanism responsible for the inhibitory effect of resveratrol. Results. The activation of NF-kappaB in chondrocytes by IL-1beta induced IL-6 secretion. The latter will then activate STAT3 protein in macrophages. Moreover, STAT3 was able to positively regulate IL-6 secretion, as confirmed by the doubling level of IL-6 in the coculture compared to macrophage monoculture. These experiments confirm the usefulness of the coculture model in the inflammatory arthritis-linked process as a closer biological situation to the synovial joint than separated chondrocytes and macrophages. Il also demonstrated the presence of an inflammatory amplification loop induced by IL-1beta. Resveratrol showed a strong inhibitory effect on the pro-inflammatory marker secretion. The decrease of IL-6 secretion is dependent on the NFkappaB inhibition in the chondrocytes. Such reduction of the IL-6 level can limit STAT3 activation in the macrophages, leading to the interruption of the inflammatory amplification loop. Conclusion. These results increase our understanding of the anti-inflammatory actions of resveratrol and open new potential approaches to prevent and treat osteoarthritis. PMID- 27187449 TI - Nutraceutical with Resveratrol and Omega-3 Fatty Acids Induces Autophagy in ARPE 19 Cells. AB - Impaired autophagic and proteasomal cleansing have been documented in aged retinal pigment epithelial (RPE) cells and age-related macular degeneration (AMD). Omega-3 fatty acids and resveratrol have many positive homeostatic effects in RPE cells. In this work, ARPE-19 cells were treated with 288 ng of Resvega, containing 30 mg of trans resveratrol and 665 mg of omega-3 fatty acids, among other nutrients, with proteasome inhibitor MG-132 or autophagy inhibitor bafilomycin A1 up to 48 h. Autophagy markers p62/SQSTM1 (p62) and LC3 (microtubule-associated protein 1A/1B-light chain 3) were analyzed by Western blotting. Fluorescence microscopy with mCherry-GFP-LC3 plasmid was applied to study the autophagy flux, and cytoprotective effects were investigated with colorimetric MTT and LDH assays. Resvega induced autophagy by showing increased autolysosome formation and autophagy flux, and the change in the p62 and LC3 protein levels further confirmed the fluorescent microscopy results. Moreover, Resvega provided a clear cytoprotection under proteasome inhibition. These findings highlight the potential of the nutraceuticals containing resveratrol, omega-3 fatty acids and other nutrients in the prevention of ARPE-19 cell damage. PMID- 27187450 TI - Review of Infant Feeding: Key Features of Breast Milk and Infant Formula. AB - Mothers' own milk is the best source of nutrition for nearly all infants. Beyond somatic growth, breast milk as a biologic fluid has a variety of other benefits, including modulation of postnatal intestinal function, immune ontogeny, and brain development. Although breastfeeding is highly recommended, breastfeeding may not always be possible, suitable or solely adequate. Infant formula is an industrially produced substitute for infant consumption. Infant formula attempts to mimic the nutritional composition of breast milk as closely as possible, and is based on cow's milk or soymilk. A number of alternatives to cow's milk-based formula also exist. In this article, we review the nutritional information of breast milk and infant formulas for better understanding of the importance of breastfeeding and the uses of infant formula from birth to 12 months of age when a substitute form of nutrition is required. PMID- 27187451 TI - Protein-Pacing from Food or Supplementation Improves Physical Performance in Overweight Men and Women: The PRISE 2 Study. AB - We recently reported that protein-pacing (P; six meals/day @ 1.4 g/kg body weight (BW), three of which included whey protein (WP) supplementation) combined with a multi-mode fitness program consisting of resistance, interval sprint, stretching, and endurance exercise training (RISE) improves body composition in overweight individuals. The purpose of this study was to extend these findings and determine whether protein-pacing with only food protein (FP) is comparable to WP supplementation during RISE training on physical performance outcomes in overweight/obese individuals. Thirty weight-matched volunteers were prescribed RISE training and a P diet derived from either whey protein supplementation (WP, n = 15) or food protein sources (FP, n = 15) for 16 weeks. Twenty-one participants completed the intervention (WP, n = 9; FP, n = 12). Measures of body composition and physical performance were significantly improved in both groups (p < 0.05), with no effect of protein source. Likewise, markers of cardiometabolic disease risk (e.g., LDL (low-density lipoprotein) cholesterol, glucose, insulin, adiponectin, systolic blood pressure) were significantly improved (p < 0.05) to a similar extent in both groups. These results demonstrate that both whey protein and food protein sources combined with multimodal RISE training are equally effective at improving physical performance and cardiometabolic health in obese individuals. PMID- 27187452 TI - Gut Microbiota and Metabolic Health: The Potential Beneficial Effects of a Medium Chain Triglyceride Diet in Obese Individuals. AB - Obesity and associated metabolic complications, such as non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D), are in constant increase around the world. While most obese patients show several metabolic and biometric abnormalities and comorbidities, a subgroup of patients representing 3% to 57% of obese adults, depending on the diagnosis criteria, remains metabolically healthy. Among many other factors, the gut microbiota is now identified as a determining factor in the pathogenesis of metabolically unhealthy obese (MUHO) individuals and in obesity-related diseases such as endotoxemia, intestinal and systemic inflammation, as well as insulin resistance. Interestingly, recent studies suggest that an optimal healthy-like gut microbiota structure may contribute to the metabolically healthy obese (MHO) phenotype. Here, we describe how dietary medium chain triglycerides (MCT), previously found to promote lipid catabolism, energy expenditure and weight loss, can ameliorate metabolic health via their capacity to improve both intestinal ecosystem and permeability. MCT-enriched diets could therefore be used to manage metabolic diseases through modification of gut microbiota. PMID- 27187453 TI - Quercetin Impacts Expression of Metabolism- and Obesity-Associated Genes in SGBS Adipocytes. AB - Obesity is characterized by the rapid expansion of visceral adipose tissue, resulting in a hypoxic environment in adipose tissue which leads to a profound change of gene expression in adipocytes. As a consequence, there is a dysregulation of metabolism and adipokine secretion in adipose tissue leading to the development of systemic inflammation and finally resulting in the onset of metabolic diseases. The flavonoid quercetin as well as other secondary plant metabolites also referred to as phytochemicals have anti-oxidant, anti inflammatory, and anti-diabetic effects known to be protective in view of obesity related-diseases. Nevertheless, its underlying molecular mechanism is still obscure and thus the focus of this study was to explore the influence of quercetin on human SGBS (Simpson Golabi Behmel Syndrome) adipocytes' gene expression. We revealed for the first time that quercetin significantly changed expression of adipokine (Angptl4, adipsin, irisin and PAI-1) and glycolysis involved (ENO2, PFKP and PFKFB4) genes, and that this effect not only antagonized but in part even overcompensated the effect mediated by hypoxia in adipocytes. Thus, these results are explained by the recently proposed hypothesis that the protective effect of quercetin is not solely due to its free radical-scavenging activity but also to a direct effect on mitochondrial processes, and they demonstrate that quercetin might have the potential to counteract the development of obesity-associated complications. PMID- 27187455 TI - Walnut Polyphenol Extract Attenuates Immunotoxicity Induced by 4-Pentylphenol and 3-methyl-4-nitrophenol in Murine Splenic Lymphocyte. AB - 4-pentylphenol (PP) and 3-methyl-4-nitrophenol (PNMC), two important components of vehicle emissions, have been shown to confer toxicity in splenocytes. Certain natural products, such as those derived from walnuts, exhibit a range of antioxidative, antitumor, and anti-inflammatory properties. Here, we investigated the effects of walnut polyphenol extract (WPE) on immunotoxicity induced by PP and PNMC in murine splenic lymphocytes. Treatment with WPE was shown to significantly enhance proliferation of splenocytes exposed to PP or PNMC, characterized by increases in the percentages of splenic T lymphocytes (CD3+ T cells) and T cell subsets (CD4+ and CD8+ T cells), as well as the production of T cell-related cytokines and granzymes (interleukin-2, interleukin-4, and granzyme B) in cells exposed to PP or PNMC. These effects were associated with a decrease in oxidative stress, as evidenced by changes in OH, SOD, GSH-Px, and MDA levels. The total phenolic content of WPE was 34,800 +/- 200 mg gallic acid equivalents/100 g, consisting of at least 16 unique phenols, including ellagitannins, quercetin, valoneic acid dilactone, and gallic acid. Taken together, these results suggest that walnut polyphenols significantly attenuated PP and PNMC-mediated immunotoxicity and improved immune function by inhibiting oxidative stress. PMID- 27187454 TI - Inositol Hexaphosphate and Inositol Inhibit Colorectal Cancer Metastasis to the Liver in BALB/c Mice. AB - Inositol hexaphosphate (IP6) and inositol (Ins), naturally occurring carbohydrates present in most mammals and plants, inhibit the growth of numerous cancers both in vitro and in vivo. In this study, we first examined the anti metastatic effects of IP6 and Ins using a liver metastasis model of colorectal cancer (CRC) in BALB/c mice. CT-26 cells were injected into the splenic capsule of 48 BALB/c mice. The mice were then randomly divided into four groups: IP6, Ins, IP6 + Ins and normal saline control (n = 12 per group). IP6 and/or Ins (80 mg/kg each, 0.2 mL/day) were injected into the gastrointestinal tracts of the mice on the second day after surgery. All mice were sacrificed after 20 days, and the tumor inhibition rates were determined. The results demonstrated that the tumor weights of liver metastases and the tumor inhibition rates were reduced in the experimental groups compared to the control group and that treatment with the combination of IP6 and Ins resulted in greater inhibition of tumor growth than treatment with either compound alone. These findings suggest that IP6 and Ins prevent the development and metastatic progression of colorectal cancer to the liver in mice by altering expression of the extracellular matrix proteins collagen IV, fibronectin and laminin; the adhesion factor receptor integrin beta1; the proteolytic enzyme matrix metalloproteinase 9; and the angiogenic factors vascular endothelial growth factor, basic fibroblast growth factor, and transforming growth factor beta in the tumor metastasis microenvironment. In conclusion, IP6 and Ins inhibited the development and metastatic progression of colorectal cancer to the liver in BALB/c mice, and the effect of their combined application was significantly greater than the effect of either compound alone. This evidence supports further testing of the combined application of IP6 and Ins for the prevention of colorectal cancer metastasis to the liver in clinical studies. PMID- 27187456 TI - High Prevalence of Vitamin D Deficiency in Cambodian Women: A Common Deficiency in a Sunny Country. AB - Recent studies have shown that in spite of being generally close to the equator; vitamin D deficiency is common in South East Asian countries. In order to quantify micronutrient status for women and children in Cambodia; a nationally representative survey was conducted in 2014 linked to the Cambodian Demographic Health Survey. The countrywide median of 25(OH)D was, respectively, 64.9 and 91.1 nmol/L for mothers and children. Based on The Endocrine Society cutoffs (>50<75 nmol/L = insufficiency; <=50 nmol/L = deficiency); 64.6% of mothers and 34.8% of their children had plasma vitamin D concentrations indicating insufficiency or deficiency. For deficiency alone, 29% of the mothers were found to be vitamin D deficient, but only 13.4% of children. Children who live in urban areas had a 43% higher rate of vitamin D insufficiency versus those who live in rural areas (OR; 1.434; 95% CI: 1.007; 2.041). However, such differences were not observed in their mothers. The high prevalence of vitamin D deficiency is likely in part due to lifestyle choices, including sun avoidance, increasingly predominant indoor work, and covered transport. These survey findings support the need for a broader national Cambodian study incorporating testing of adult men, adolescents and the elderly, and encompassing other parameters such as skeletal health. However, the data presented in this study already show significant deficiencies which need to be addressed and we discuss the benefit of establishing nationally-mandated food fortification programs to enhance the intake of vitamin D. PMID- 27187457 TI - Effects of Low-Fat Diets Differing in Protein and Carbohydrate Content on Cardiometabolic Risk Factors during Weight Loss and Weight Maintenance in Obese Adults with Type 2 Diabetes. AB - Despite evidence for the benefits of higher-protein (HP) diets in weight loss, their role in type 2 diabetes mellitus (T2DM) management and weight maintenance is not clear. This randomised study compared the effects of a HP diet (38% carbohydrate, 30% protein, 29% fat) to a isocaloric higher-carbohydrate diet (HC: 53%:21%:23%) on cardiometabolic risk factors for 12 weeks in energy restriction (~30% reduction) followed by 12 weeks of energy balance whilst performing regular exercise. Outcomes were measured at baseline and the end of each phase. Sixty-one overweight/obese adults (BMI (body mass index) 34.3 +/- 5.1 kg/m2, aged 55 +/- 8 years) with T2DM who commenced the study were included in the intention-to-treat analysis including the 17 participants (HP n = 9, HC n = 8) who withdrew. Following weight loss (M +/- SEM: -7.8 +/- 0.6 kg), there were significant reductions in HbA1c (-1.4% +/- 0.1%, p < 0.001) and several cardiometabolic health risk factors. Improvements were sustained for 12 weeks when weight was stabilised and weight loss maintained. Both the HP and HC dietary patterns with concurrent exercise may be effective strategies for weight loss and weight maintenance in T2DM although further studies are needed to determine the longer term effects of weight maintenance. PMID- 27187458 TI - Hawthorn Fruit Extract Elevates Expression of Nrf2/HO-1 and Improves Lipid Profiles in Ovariectomized Rats. AB - The purpose of this study was to investigate the effects of hawthorn (Crataegus pinnatifida Bunge) extract on the lipid profiles and antioxidant properties in ovariectomized (OVX) rats. After ovariectomy, the rats were randomly divided into four groups: the non-OVX control (Sham), the OVX-control (OVX), the OVX + 100 mg/kg b.w. of hawthorn extract (OL), and the OVX + 200 mg/kg b.w. of hawthorn extract (OH). The final body weights of the OVX group were significantly increased, but the increment was significantly decreased in hawthorn groups (p < 0.05). The serum total and low-density lipoprotein (LDL) cholesterol levels were significantly elevated in the OVX group, whereas the hawthorn groups showed a significant decrease in these levels (p < 0.05). The hepatic triglyceride (TG) and malondialdehyde (MDA) levels were significantly reduced in the hawthorn groups compared with the OVX group (p < 0.05). The mRNA expression of nuclear factor erythroid 2-related factor (Nrf2), heme oxygenase-1 (HO-1), and glutathione peroxidase (GPx) were significantly decreased in the OVX group, whereas the hawthorn groups exhibited a significant increase in expression (p < 0.05). The protein expressions of Nrf2, HO-1, and GPx were lower in the OVX group than the Sham group (p < 0.05). The oral administration of hawthorn extract reversed the suppression of protein levels. These results suggest that hawthorn extract could have protective effects in OVX rats by improving lipid profiles, decreasing oxidative stress, and improving the antioxidant defense system. PMID- 27187459 TI - Dietary Intake of the Urban Black Population of Cape Town: The Cardiovascular Risk in Black South Africans (CRIBSA) Study. AB - INTRODUCTION: To determine dietary intake of 19 to 64 years old urban Africans in Cape Town in 2009 and examine the changes between 1990 and 2009. METHODS: A representative cross-sectional sample (n = 544), stratified by gender and age was randomly selected in 2009 from the same areas sampled in 1990. Socio-demographic data and a 24-h dietary recall were obtained by trained field workers. The associations of dietary data with an asset index and degree of urbanization were assessed. RESULTS: Fat intakes were higher in 19-44-year-old men (32% energy (E)) and women (33.4%E) in 2009 compared with 1990 (men: 25.9%E, women: 27.0%E) while carbohydrate intakes were lower in 2009 (men 53.2%E, women: 55.5%E) than in 1990 (men: 61.3%E; women: 62%E) while sugar intake increased significantly (p < 0.01) in women. There were significant positive correlations between urbanization and total fat (p = 0.016), saturated fat (p = 0.001), monounsaturated fat (p = 0.002) and fat as a %E intake (p = 0.046). Urbanization was inversely associated with intake of carbohydrate %E (p < 0.001). Overall micronutrient intakes improved significantly compared with 1990. It should also be noted that energy and macronutrient intakes were all significant in a linear regression model using mean adequacy ratio (MAR) as a measure of dietary quality in 2009, as was duration of urbanization. DISCUSSION: The higher fat and lower carbohydrate %E intakes in this population demonstrate a transition to a more urbanized diet over last two decades. These dietary changes reflect the nutrition transitions that typically occur as a longer time is spent in urban centers. PMID- 27187460 TI - Role of Vitamin D in Cognitive Function in Chronic Kidney Disease. AB - Both vitamin D deficiency and cognitive impairment are common in patients with chronic kidney disease (CKD). Vitamin D exerts neuroprotective and regulatory roles in the central nervous system. Hypovitaminosis D has been associated with muscle weakness and bone loss, cardiovascular diseases (hypertension, diabetes and hyperlipidemia), inflammation, oxidative stress, immune suppression and neurocognitive impairment. The combination of hypovitaminosis D and CKD can be even more debilitating, as cognitive impairment can develop and progress through vitamin D-associated and CKD-dependent/independent processes, leading to significant morbidity and mortality. Although an increasingly recognized comorbidity in CKD, cognitive impairment remains underdiagnosed and often undermanaged. Given the association of cognitive decline and hypovitaminosis D and their deleterious effects in CKD patients, determination of vitamin D status and when appropriate, supplementation, in conjunction with neuropsychological screening, should be considered integral to the clinical care of the CKD population. PMID- 27187461 TI - Infant Feeding Practices in a Multi-Ethnic Asian Cohort: The GUSTO Study. AB - The optimal introduction of complementary foods provides infants with nutritionally balanced diets and establishes healthy eating habits. The documentation of infant feeding practices in multi-ethnic Asian populations is limited. In a Singapore cohort study (GUSTO), 842 mother-infant dyads were interviewed regarding their feeding practices when the infants were aged 9 and 12 months. In the first year, 20.5% of infants were given dietary supplements, while 5.7% took probiotics and 15.7% homeopathic preparations. At age 9 months, 45.8% of infants had seasonings added to their foods, increasing to 56.3% at 12 months. At age 12 months, 32.7% of infants were given blended food, although 92.3% had begun some form of self-feeding. Additionally, 87.4% of infants were fed milk via a bottle, while a third of them had food items added into their bottles. At both time points, more than a third of infants were provided sweetened drinks via the bottle. Infants of Indian ethnicity were more likely to be given dietary supplements, have oil and seasonings added to their foods and consumed sweetened drinks from the bottle (p < 0.001). These findings provide a better understanding of variations in infant feeding practices, so that healthcare professionals can offer more targeted and culturally-appropriate advice. PMID- 27187462 TI - The Economic Burden of Malnutrition in Pregnant Women and Children under 5 Years of Age in Cambodia. AB - Malnutrition is locked in a vicious cycle of increased mortality, poor health, impaired cognitive development, slow physical growth, reduced learning capacity, inferior performance, and ultimately lower adult work performance and productivity. The consensus of global scientific evidence indicates that lowering the rates of malnutrition will be an indispensable component of any successful program to raise the quality of human capital and resources. This study used a "consequence model" to apply the coefficient risk-deficit on economic losses, established in the global scientific literature, to Cambodian health, demographic, and economic data to develop a national estimate of the value of economic losses due to malnutrition. The impact of the indicators of malnutrition analyzed represent a burden to the national economy of Cambodia estimated at 266 million USD annually (1.7% of GDP). Stunting is reducing the Cambodian economic output by more than 120 million USD, and iodine deficiency disorders alone by 57 million USD. This economic burden is too high in view of Cambodia's efforts to drive economic development. The government should rapidly expand a range of low cost effective nutrition interventions to break the current cycle of increased mortality, poor health and ultimately lower work performance, productivity, and earnings. PMID- 27187464 TI - Diet Quality and Adequacy of Nutrients in Preschool Children: Should Rice Fortified with Micronutrients Be Included in School Meals? AB - Feeding is indicative of the nutritional status of children, however micronutrient deficiency is common in this age group. We evaluated the impact of inclusion of rice (Ultra Rice((r)) (UR((r)))) fortified with iron, zinc, thiamin and folic acid on laboratory measurements and the nutrient intake of children. Ninety-nine preschoolers (2-6 years; 42.6% male) from two preschools participated, one of which received UR((r)) added to polished rice as part of school meals (test preschool) and the other received only polished rice (control preschool). Biochemical evaluations were performed before and after four months of intervention. Feeding was assessed by direct weighing of food, complemented by 24-h recalls, and the diet was assessed by the Healthy Eating Index (HEI) adapted to the Brazilian reality. The fortified rice improved the levels of zinc (p < 0.001), thiamine (p < 0.001), folic acid (p = 0.003), mean corpuscular hemoglobin (p < 0.001) and mean corpuscular hemoglobin concentration (p < 0.001). The inadequacy percentages of thiamine, folic acid and iron were lower among preschoolers from the test preschool. This study demonstrated the effectiveness of using UR((r)) on laboratory measurements of children. The inadequate intake of thiamine, folic acid and iron was also reduced, making the fortified rice an interesting strategy in school feeding programs. PMID- 27187463 TI - Correlation between Nutrition and Symptoms: Nutritional Survey of Children with Autism Spectrum Disorder in Chongqing, China. AB - Restricted diets and inadequate nutrient intake of children with autism spectrum disorder (ASD) have been reported. This study examined the nutritional statuses of children with ASD and the relationships between their behaviors and nutritional intake. A total of 154 children with ASD (age = 5.21 +/- 1.83 years) and 73 typically-developing (TD) children (age = 4.83 +/- 0.84 years) from Chongqing, China, were enrolled. The severity of ASD was evaluated using the Childhood Autism Rating Scale (CARS). The serum ferritin, folate, vitamin B12, 25(OH) vitamin D, and vitamin A concentrations in the children with ASD were determined. All participants underwent anthropometric examinations, dietary assessments, and questionnaire assessments about their feeding behaviors, and gastrointestinal symptoms. The ZHA, ZWA, and ZBMIA were found to be significantly lower in the children with ASD compared with those without ASD. In addition, the percentages of children exhibiting severe picky eating and severe resistance to new foods, as well as those with a reported general impression of severe eating problems and constipation, were higher among the children with ASD. These children consumed significantly fewer macronutrients compared with the children without ASD. In addition, the children with ASD had the highest rate of vitamin A deficiency, followed by iron deficiency. After adjusting for sex, the vitamin A concentration was found to be negatively correlated with the CARS score (rs = 0.222, p = 0.021). No correlation between the ferritin, folate, vitamin D, or vitamin B12 concentration and the CARS score was found. These results suggest that reduced macronutrient intakes, severe feeding behavior issues, constipation, and vitamin A deficiency are quite common among children with ASD. Further, a low serum vitamin A level may be a risk factor for symptoms of ASD. However, the underlying mechanism should be further studied. PMID- 27187465 TI - Protein Intake and Muscle Health in Old Age: From Biological Plausibility to Clinical Evidence. AB - The provision of sufficient amounts of dietary proteins is central to muscle health as it ensures the supply of essential amino acids and stimulates protein synthesis. Older persons, in particular, are at high risk of insufficient protein ingestion. Furthermore, the current recommended dietary allowance for protein (0.8 g/kg/day) might be inadequate for maintaining muscle health in older adults, probably as a consequence of "anabolic resistance" in aged muscle. Older individuals therefore need to ingest a greater quantity of protein to maintain muscle function. The quality of protein ingested is also essential to promoting muscle health. Given the role of leucine as the master dietary regulator of muscle protein turnover, the ingestion of protein sources enriched with this essential amino acid, or its metabolite beta-hydroxy beta-methylbutyrate, is thought to offer the greatest benefit in terms of preservation of muscle mass and function in old age. PMID- 27187466 TI - The Draft Genome Sequence of the Yersinia entomophaga Entomopathogenic Type Strain MH96T. AB - Here we report the draft genome of Yersinia entomophaga type strain MH96T. The genome shows 93.8% nucleotide sequence identity to that of Yersinia nurmii type strain APN3a-cT, and comprises a single chromosome of approximately 4,275,531 bp. In silico analysis identified that, in addition to the previously documented Y. entomophaga Yen-TC gene cluster, the genome encodes a diverse array of toxins, including two type III secretion systems, and five rhs-associated gene clusters. As well as these multicomponent systems, several orthologs of known insect toxins, such as VIP2 toxin and the binary toxin PirAB, and distant orthologs of some mammalian toxins, including repeats-in-toxin, a cytolethal distending toxin, hemolysin-like genes and an adenylate cyclase were identified. The genome also contains a large number of hypothetical proteins and orthologs of known effector proteins, such as LopT, as well as genes encoding a wide range of proteolytic determinants, including metalloproteases and pathogen fitness determinants, such as genes involved in iron metabolism. The bioinformatic data derived from the current in silico analysis, along with previous information on the pathobiology of Y. entomophaga against its insect hosts, suggests that a number of these virulence systems are required for survival in the hemocoel and incapacitation of the insect host. PMID- 27187468 TI - Report from the 5th International Symposium on Mycotoxins and Toxigenic Moulds: Challenges and Perspectives (MYTOX) Held in Ghent, Belgium, May 2016. AB - The association research platform MYTOX "Mycotoxins and Toxigenic Moulds" held the 5th meetingofitsInternationalSymposiuminGhent,Belgiumon11May2016.[...]. PMID- 27187467 TI - Two Novel Dermaseptin-Like Antimicrobial Peptides with Anticancer Activities from the Skin Secretion of Pachymedusa dacnicolor. AB - The dermaseptin antimicrobial peptide family contains members of 27-34 amino acids in length that have been predominantly isolated from the skins/skin secretions of phyllomedusine leaf frogs. By use of a degenerate primer in Rapid amplification of cDNA ends (RACE) PCR designed to a common conserved domain within the 5'-untranslated regions of previously-characterized dermaseptin encoding cDNAs, two novel members of this peptide family, named dermaseptin-PD-1 and dermaseptin-PD-2, were identified in the skin secretion of the phyllomedusine frog, Pachymedusa dacnicolor. The primary structures of both peptides were predicted from cloned cDNAs, as well as being confirmed by mass spectral analysis of crude skin secretion fractions resulted from reversed-phase high-performance liquid chromatography. Chemically-synthesized replicates of dermaseptin-PD-1 and dermaseptin-PD-2 were investigated for antimicrobial activity using standard model microorganisms (Gram-positive bacteria, Gram-negative bacteria and a yeast) and for cytotoxicity using mammalian red blood cells. The possibility of synergistic effects between the two peptides and their anti-cancer cell proliferation activities were assessed. The peptides exhibited moderate to high inhibition against the growth of the tested microorganisms and cancer cell lines with low haemolytic activity. Synergistic interaction between the two peptides in inhibiting the proliferation of Escherichia coli and human neuronal glioblastoma cell line, U251MG was also manifested. PMID- 27187470 TI - Monoclonal IgA Antibodies for Aflatoxin Immunoassays. AB - Antibody based techniques are widely used for the detection of aflatoxins which are potent toxins with a high rate of occurrence in many crops. We developed a murine monoclonal antibody of immunoglobulin A (IgA) isotype with a strong binding affinity to aflatoxin B1 (AFB1), aflatoxin B2 (AFB2), aflatoxin G1 (AFG1), aflatoxin G2 (AFG2) and aflatoxin M1 (AFM1). The antibody was effectively used in immunoaffinity column (IAC) and ELISA kit development. The performance of the IACs was compatible with AOAC performance standards for affinity columns (Test Method: AOAC 991.31). The total binding capacity of the IACs containing our antibody was 111 ng, 70 ng, 114 ng and 73 ng for AFB1, AFB2, and AFG1 andAFG2, respectively. Furthermore, the recovery rates of 5 ng of each AF derivative loaded to the IACs were determined as 104.9%, 82.4%, 85.5% and 70.7% for AFB1, AFB2, AFG1 and AFG2, respectively. As for the ELISA kit developed using non oriented, purified IgA antibody, we observed a detection range of 2-50 ug/L with 40 min total test time. The monoclonal antibody developed in this research is hitherto the first presentation of quadruple antigen binding IgA monoclonal antibodies in mycotoxin analysis and also the first study of their utilization in ELISA and IACs. IgA antibodies are valuable alternatives for immunoassay development, in terms of both sensitivity and ease of preparation, since they do not require any orientation effort. PMID- 27187469 TI - Withania somnifera Induces Cytotoxic and Cytostatic Effects on Human T Leukemia Cells. AB - Cancer chemotherapy is characterized by an elevated intrinsic toxicity and the development of drug resistance. Thus, there is a compelling need for new intervention strategies with an improved therapeutic profile. Immunogenic cell death (ICD) represents an innovative anticancer strategy where dying cancer cells release damage-associated molecular patterns promoting tumor-specific immune responses. The roots of Withania somnifera (W. somnifera) are used in the Indian traditional medicine for their anti-inflammatory, immunomodulating, neuroprotective, and anticancer activities. The present study is designed to explore the antileukemic activity of the dimethyl sulfoxide extract obtained from the roots of W. somnifera (WE). We studied its cytostatic and cytotoxic activity, its ability to induce ICD, and its genotoxic potential on a human T lymphoblastoid cell line by using different flow cytometric assays. Our results show that WE has a significant cytotoxic and cytostatic potential, and induces ICD. Its proapoptotic mechanism involves intracellular Ca(2+) accumulation and the generation of reactive oxygen species. In our experimental conditions, the extract possesses a genotoxic potential. Since the use of Withania is suggested in different contexts including anti-infertility and osteoarthritis care, its genotoxicity should be carefully considered for an accurate assessment of its risk-benefit profile. PMID- 27187471 TI - Determination of Asymmetric and Symmetric Dimethylarginine in Serum from Patients with Chronic Kidney Disease: UPLC-MS/MS versus ELISA. AB - Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthesis, and its structural isomer symmetric dimethylarginine (SDMA) are uremic toxins accumulating in chronic kidney disease (CKD) patients. The objective of this study was to develop and validate a robust UPLC-MS/MS method for the simultaneous determination of ADMA and SDMA in human serum. Chromatographic separation after butyl ester derivatization was achieved on an Acquity UPLC BEH C18 column, followed by tandem mass spectrometric detection. After validation, the applicability of the method was evaluated by the analysis of serum samples from 10 healthy controls and 77 CKD patients on hemodialysis (CKD5HD). Both ADMA (0.84 +/- 0.19 uM vs. 0.52 +/- 0.07 uM) and SDMA concentrations (2.06 +/- 0.82 uM vs. 0.59 +/- 0.13 uM) were significantly (p < 0.001) elevated in CKD5HD patients compared to healthy controls. In general, low degrees of protein binding were found for both ADMA and SDMA. In addition, an established commercially available ELISA kit was utilized on the same samples (n = 87) to compare values obtained both with ELISA and UPLC-MS/MS. Regression analysis between these two methods was significant (p < 0.0001) but moderate for both ADMA (R = 0.78) and SDMA (R = 0.72). PMID- 27187473 TI - New Insights into VacA Intoxication Mediated through Its Cell Surface Receptors. AB - Helicobacter pylori (H. pylori), a major cause of gastroduodenal diseases, produces VacA, a vacuolating cytotoxin associated with gastric inflammation and ulceration. The C-terminal domain of VacA plays a crucial role in receptor recognition on target cells. We have previously identified three proteins (i.e., RPTPalpha, RPTPbeta, and LRP1) that serve as VacA receptors. These receptors contribute to the internalization of VacA into epithelial cells, activate signal transduction pathways, and contribute to cell death and gastric ulceration. In addition, other factors (e.g., CD18, sphingomyelin) have also been identified as cell-surface, VacA-binding proteins. Since we believe that, following interactions with its host cell receptors, VacA participates in events leading to disease, a better understanding of the cellular function of VacA receptors may provide valuable information regarding the mechanisms underlying the pleiotropic actions of VacA and the pathogenesis of H. pylori-mediated disease. In this review, we focus on VacA receptors and their role in events leading to cell damage. PMID- 27187474 TI - Sensitive, Rapid, Quantitative and in Vitro Method for the Detection of Biologically Active Staphylococcal Enterotoxin Type E. AB - Staphylococcus aureus is a major bacterial cause of clinical infections and foodborne illnesses through its production of a group of enterotoxins (SEs) which cause gastroenteritis and also function as superantigens to massively activate T cells. In the present study, we tested Staphylococcal enterotoxin type E (SEE), which was detected in 17 of the 38 suspected staphylococcal food poisoning incidents in a British study and was the causative agent in outbreaks in France, UK and USA. The current method for detection of enterotoxin activity is an in vivo monkey or kitten bioassay; however, this expensive procedure has low sensitivity and poor reproducibility, requires many animals, is impractical to test on a large number of samples, and raises ethical concerns with regard to the use of experimental animals. The purpose of this study is to develop rapid sensitive and quantitative bioassays for detection of active SEE. We apply a genetically engineered T cell-line expressing the luciferase reporter gene under the regulation of nuclear factor of activated T-cells response element (NFAT-RE), combined with a Raji B-cell line that presents the SEE-MHC (major histocompatibility complex) class II to the engineered T cell line. Exposure of the above mixed culture to SEE induces differential expression of the luciferase gene and bioluminescence is read out in a dose dependent manner over a 6-log range. The limit of detection of biologically active SEE is 1 fg/mL which is 108 times more sensitive than the monkey and kitten bioassay. PMID- 27187472 TI - Ellagitannins in Cancer Chemoprevention and Therapy. AB - It is universally accepted that diets rich in fruit and vegetables lead to reduction in the risk of common forms of cancer and are useful in cancer prevention. Indeed edible vegetables and fruits contain a wide variety of phytochemicals with proven antioxidant, anti-carcinogenic, and chemopreventive activity; moreover, some of these phytochemicals also display direct antiproliferative activity towards tumor cells, with the additional advantage of high tolerability and low toxicity. The most important dietary phytochemicals are isothiocyanates, ellagitannins (ET), polyphenols, indoles, flavonoids, retinoids, tocopherols. Among this very wide panel of compounds, ET represent an important class of phytochemicals which are being increasingly investigated for their chemopreventive and anticancer activities. This article reviews the chemistry, the dietary sources, the pharmacokinetics, the evidence on chemopreventive efficacy and the anticancer activity of ET with regard to the most sensitive tumors, as well as the mechanisms underlying their clinically-valuable properties. PMID- 27187476 TI - The Wnt Target Gene L1 in Colon Cancer Invasion and Metastasis. AB - The Wnt-beta-catenin signaling pathway is highly conserved during evolution and determines normal tissue homeostasis. Hyperactivation of Wnt-beta-catenin signaling is a characteristic feature of colorectal cancer (CRC) development. beta-catenin is a major transducer of the Wnt signal from the cytoplasm into the nucleus where it acts as a co-transcriptional activator of beta-catenin-TCF target genes. beta-catenin is also required for linking cadherin type cell-cell adhesion receptors to the cytoskeleton, and consequently Wnt-beta-catenin signaling is an attractive system for investigating the role of adhesion-mediated signaling in both normal intestinal tissue homeostasis and CRC development. In this review, we summarize our studies on one Wnt-beta-catenin target gene, L1, a member of the immunoglobulin-like cell adhesion transmembrane receptor family. We describe the mechanisms of L1-mediated signaling in CRC cells, its exclusive localization in invasive areas of CRC tissue, and its ability to increase cell motility and confer metastasis to the liver. We discuss the activation (by L1) of genes via an ezrin-NF-kappaB pathway and the induction of genes also found in the intestinal stem cell signature. By studying L1 (adhesion)-mediated signaling, we expect to learn about mechanisms regulating both normal intestinal homeostasis and CRC development. PMID- 27187477 TI - In Hyperthermia Increased ERK and WNT Signaling Suppress Colorectal Cancer Cell Growth. AB - Although neoplastic cells exhibit relatively higher sensitivity to hyperthermia than normal cells, hyperthermia has had variable success as an anti-cancer therapy. This variable outcome might be due to the fact that cancer cells themselves have differential degrees of sensitivity to high temperature. We hypothesized that the varying sensitivity of colorectal cancer (CRC) cells to hyperthermia depends upon the differential induction of survival pathways. Screening of such pathways revealed that Extracellular Signal-Regulated Kinase (ERK) signaling is augmented by hyperthermia, and the extent of this modulation correlates with the mutation status of V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS). Through clonal growth assays, apoptotic analyses and transcription reporter assays of CRC cells that differ only in KRAS mutation status we established that mutant KRAS cells are more sensitive to hyperthermia, as they exhibit sustained ERK signaling hyperactivation and increased Wingless/Integrated (WNT)/beta-catenin signaling. We propose that whereas increased levels of WNT and ERK signaling and a positive feedback between the two pathways is a major obstacle in anti-cancer therapy today, under hyperthermia the hyperinduction of the pathways and their positive crosstalk contribute to CRC cell death. Ascertaining the causative association between types of mutations and hyperthermia sensitivity may allow for a mutation profile-guided application of hyperthermia as an anti-cancer therapy. Since KRAS and WNT signaling mutations are prevalent in CRC, our results suggest that hyperthermia-based therapy might benefit a significant number, but not all, CRC patients. PMID- 27187475 TI - The Regulatory Networks That Control Clostridium difficile Toxin Synthesis. AB - The pathogenic clostridia cause many human and animal diseases, which typically arise as a consequence of the production of potent exotoxins. Among the enterotoxic clostridia, Clostridium difficile is the main causative agent of nosocomial intestinal infections in adults with a compromised gut microbiota caused by antibiotic treatment. The symptoms of C. difficile infection are essentially caused by the production of two exotoxins: TcdA and TcdB. Moreover, for severe forms of disease, the spectrum of diseases caused by C. difficile has also been correlated to the levels of toxins that are produced during host infection. This observation strengthened the idea that the regulation of toxin synthesis is an important part of C. difficile pathogenesis. This review summarizes our current knowledge about the regulators and sigma factors that have been reported to control toxin gene expression in response to several environmental signals and stresses, including the availability of certain carbon sources and amino acids, or to signaling molecules, such as the autoinducing peptides of quorum sensing systems. The overlapping regulation of key metabolic pathways and toxin synthesis strongly suggests that toxin production is a complex response that is triggered by bacteria in response to particular states of nutrient availability during infection. PMID- 27187481 TI - Hans Georg Truper (1936-2016) and His Contributions to Halophile Research. AB - Prof. Hans Georg Truper, one of the most important scientists in the field of halophile research, passed away on 9 March 2016 at the age of 79. I here present a brief obituary with special emphasis on Prof. Truper's contributions to our understanding of the halophilic prokaryotes and their adaptations to life in hypersaline environments. He has pioneered the study of the halophilic anoxygenic phototrophic sulfur bacteria of the Ectothiorhodospira-Halorhodospira group. Some of the species he and his group isolated from hypersaline and haloalkaline environments have become model organisms for the study of the mechanisms of haloadaptation: the functions of three major organic compounds - glycine betaine, ectoine, and trehalose - known to serve as "compatible solutes" in halophilic members of the Bacteria domain, were discovered during studies of these anoxygenic phototrophs. Prof. Truper's studies of hypersaline alkaline environments in Egypt also led to the isolation of the first known extremely halophilic archaeon (Natronomonas pharaonis). The guest editors dedicate this special volume of Life to the memory of Prof. Hans Georg Truper. PMID- 27187480 TI - The Complete Chloroplast Genome of the Hare's Ear Root, Bupleurum falcatum: Its Molecular Features. AB - Bupleurum falcatum, which belongs to the family Apiaceae, has long been applied for curative treatments, especially as a liver tonic, in herbal medicine. The chloroplast (cp) genome has been an ideal model to perform the evolutionary and comparative studies because of its highly conserved features and simple structure. The Apiaceae family is taxonomically close to the Araliaceae family and there have been numerous complete chloroplast genome sequences reported in the Araliaceae family, while little is known about the Apiaceae family. In this study, the complete sequence of the B. falcatum chloroplast genome was obtained. The full-length of the cp genome is 155,989 nucleotides with a 37.66% overall guanine-cytosine (GC) content and shows a quadripartite structure composed of three nomenclatural regions: a large single-copy (LSC) region, a small single copy (SSC) region, and a pair of inverted repeat (IR) regions. The genome occupancy is 85,912-bp, 17,517-bp, and 26,280-bp for LSC, SSC, and IR, respectively. B. falcatum was shown to contain 111 unique genes (78 for protein coding, 29 for tRNAs, and four for rRNAs, respectively) on its chloroplast genome. Genic comparison found that B. falcatum has no pseudogenes and has two gene losses, accD in the LSC and ycf15 in the IRs. A total of 55 unique tandem repeat sequences were detected in the B. falcatum cp genome. This report is the first to describe the complete chloroplast genome sequence in B. falcatum and will open up further avenues of research to understand the evolutionary panorama and the chloroplast genome conformation in related plant species. PMID- 27187482 TI - (18)F-FDG PET/CT Findings in Acute Epstein-Barr Virus Infection Mimicking Malignant Lymphoma. AB - We present a case demonstrating the diagnostic work-up and follow-up of a patient with acute Epstein-Barr virus (EBV) infection in which the clinical picture and imaging on (18)F-FDG PET/CT mimicked malignant lymphoma. Follow-up (18)F-FDG PET/CT scan in the patient performed 7 weeks after the abnormal scan revealed complete resolution of the metabolically active disease in the neck, axillas, lung hili, and spleen. This case highlights inflammation as one of the most well established false positives when interpreting (18)F-FDG PET/CT scans. PMID- 27187483 TI - Comprehensive Characterization of Reference Standard Lots of HIV-1 Subtype C Gp120 Proteins for Clinical Trials in Southern African Regions. AB - Two HIV-1 subtype C gp120 protein candidates were the selected antigens for several experimental vaccine regimens now under evaluation in HVTN 100 Phase I/II clinical trial aiming to support the start of the HVTN 702 Phase IIb/III trial in southern Africa, which is designed to confirm and extend the partial protection seen against HIV-1 infection in the RV144 Thai trial. Here, we report the comprehensive physicochemical characterization of the gp120 reference materials that are representative of the clinical trial materials. Gp120 proteins were stably expressed in Chinese Hamster Ovary (CHO) cells and subsequently purified and formulated. A panel of analytical techniques was used to characterize the physicochemical properties of the two protein molecules. When formulated in the AS01 Adjuvant System, the bivalent subtype C gp120 antigens elicited 1086.C- and TV1.C-specific binding antibody and CD4+ T cell responses in mice. All the characteristics were highly representative of the Clinical Trial Materials (CTM). Data from this report demonstrate the immunogenicity of the gp120 antigens, provide comprehensive characterization of the molecules, set the benchmark for assessment of current and future CTM lots, and lay the physicochemical groundwork for interpretation of future clinical trial data. PMID- 27187478 TI - The Ubiquitination of NF-kappaB Subunits in the Control of Transcription. AB - Nuclear factor (NF)-kappaB has evolved as a latent, inducible family of transcription factors fundamental in the control of the inflammatory response. The transcription of hundreds of genes involved in inflammation and immune homeostasis require NF-kappaB, necessitating the need for its strict control. The inducible ubiquitination and proteasomal degradation of the cytoplasmic inhibitor of kappaB (IkappaB) proteins promotes the nuclear translocation and transcriptional activity of NF-kappaB. More recently, an additional role for ubiquitination in the regulation of NF-kappaB activity has been identified. In this case, the ubiquitination and degradation of the NF-kappaB subunits themselves plays a critical role in the termination of NF-kappaB activity and the associated transcriptional response. While there is still much to discover, a number of NF-kappaB ubiquitin ligases and deubiquitinases have now been identified which coordinate to regulate the NF-kappaB transcriptional response. This review will focus the regulation of NF-kappaB subunits by ubiquitination, the key regulatory components and their impact on NF-kappaB directed transcription. PMID- 27187484 TI - Linking Findings in Microfluidics to Membrane Emulsification Process Design: The Importance of Wettability and Component Interactions with Interfaces. AB - In microfluidics and other microstructured devices, wettability changes, as a result of component interactions with the solid wall, can have dramatic effects. In emulsion separation and emulsification applications, the desired behavior can even be completely lost. Wettability changes also occur in one phase systems, but the effect is much more far-reaching when using two-phase systems. For microfluidic emulsification devices, this can be elegantly demonstrated and quantified for EDGE (Edge-base Droplet GEneration) devices that have a specific behavior that allows us to distinguish between surfactant and liquid interactions with the solid surface. Based on these findings, design rules can be defined for emulsification with any micro-structured emulsification device, such as direct and premix membrane emulsification. In general, it can be concluded that mostly surface interactions increase the contact angle toward 90 degrees , either through the surfactant, or the oil that is used. This leads to poor process stability, and very limited pressure ranges at which small droplets can be made in microfluidic systems, and cross-flow membrane emulsification. In a limited number of cases, surface interactions can also lead to lower contact angles, thereby increasing the operational stability. This paper concludes with a guideline that can be used to come to the appropriate combination of membrane construction material (or any micro-structured device), surfactants and liquids, in combination with process conditions. PMID- 27187479 TI - Advances in Autophagy Regulatory Mechanisms. AB - Autophagy plays a critical role in cell metabolism by degrading and recycling internal components when challenged with limited nutrients. This fundamental and conserved mechanism is based on a membrane trafficking pathway in which nascent autophagosomes engulf cytoplasmic cargo to form vesicles that transport their content to the lysosome for degradation. Based on this simple scheme, autophagy modulates cellular metabolism and cytoplasmic quality control to influence an unexpectedly wide range of normal mammalian physiology and pathophysiology. In this review, we summarise recent advancements in three broad areas of autophagy regulation. We discuss current models on how autophagosomes are initiated from endogenous membranes. We detail how the uncoordinated 51-like kinase (ULK) complex becomes activated downstream of mechanistic target of rapamycin complex 1 (MTORC1). Finally, we summarise the upstream signalling mechanisms that can sense amino acid availability leading to activation of MTORC1. PMID- 27187485 TI - Managing Status Epilepticus in the Older Adult. AB - The aim of this systematic review was to describe particularities in epidemiology, outcome, and management modalities in the older adult population with status epilepticus. There is a higher incidence of status epilepticus in the older adult population, and it commonly has a nonconvulsive presentation. Diagnosis in this population may be difficult and requires an unrestricted use of EEG. Short and long term associated-mortality are high, and age over 60 years is an independent factor associated with poor outcome. Stroke (acute or remote symptomatic), miscellaneous metabolic causes, dementia, infections hypoxemia, and brain injury are among the main causes of status epilepticus occurrence in this age category. The use of anticonvulsive agents can be problematic as well. Thus, it is important to take into account the specific aspects related to the pharmacokinetic and pharmacodynamic changes in older critically-ill adults. Beyond these precautions, the management may be identical to that of the younger adult, including prompt initiation of symptomatic and anticonvulsant therapies, and a broad and thorough etiological investigation. Such management strategies may improve the vital and functional prognosis of these patients, while maintaining a high overall quality of care. PMID- 27187486 TI - A Flow SPR Immunosensor Based on a Sandwich Direct Method. AB - In this study, we report the development of an SPR (Surface Plasmon Resonance) immunosensor for the detection of ampicillin, operating under flow conditions. SPR sensors based on both direct (with the immobilization of the antibody) and competitive (with the immobilization of the antigen) methods did not allow the detection of ampicillin. Therefore, a sandwich-based sensor was developed which showed a good linear response towards ampicillin between 10(-3) and 10(-1) M, a measurement time of <=20 min and a high selectivity both towards beta-lactam antibiotics and antibiotics of different classes. PMID- 27187487 TI - Role of Myofibrillar Protein Catabolism in Development of Glucocorticoid Myopathy: Aging and Functional Activity Aspects. AB - Muscle weakness in corticosteroid myopathy is mainly the result of the destruction and atrophy of the myofibrillar compartment of fast-twitch muscle fibers. Decrease of titin and myosin, and the ratio of nebulin and MyHC in myopathic muscle, shows that these changes of contractile and elastic proteins are the result of increased catabolism of the abovementioned proteins in skeletal muscle. Slow regeneration of skeletal muscle is in good correlation with a decreased number of satellite cells under the basal lamina of muscle fibers. Aging causes a reduction of AMP-activated protein kinase (AMPK) activity as the result of the reduced function of the mitochondrial compartment. AMPK activity increases as a result of increased functional activity. Resistance exercise causes anabolic and anticatabolic effects in skeletal muscle: muscle fibers experience hypertrophy while higher myofibrillar proteins turn over. These changes are leading to the qualitative remodeling of muscle fibers. As a result of these changes, possible maximal muscle strength is increasing. Endurance exercise improves capillary blood supply, increases mitochondrial biogenesis and muscle oxidative capacity, and causes a faster turnover rate of sarcoplasmic proteins as well as qualitative remodeling of type I and IIA muscle fibers. The combination of resistance and endurance exercise may be the fastest way to prevent or decelerate muscle atrophy due to the anabolic and anticatabolic effects of exercise combined with an increase in oxidative capacity. The aim of the present short review is to assess the role of myofibrillar protein catabolism in the development of glucocorticoid-caused myopathy from aging and physical activity aspects. PMID- 27187489 TI - Nitrogen Assimilation, Abiotic Stress and Glucose 6-Phosphate Dehydrogenase: The Full Circle of Reductants. AB - Glucose 6 phosphate dehydrogenase (G6PDH; EC 1.1.1.49) is well-known as the main regulatory enzyme of the oxidative pentose phosphate pathway (OPPP) in living organisms. Namely, in Planta, different G6PDH isoforms may occur, generally localized in cytosol and plastids/chloroplasts. These enzymes are differently regulated by distinct mechanisms, still far from being defined in detail. In the last decades, a pivotal function for plant G6PDHs during the assimilation of nitrogen, providing reductants for enzymes involved in nitrate reduction and ammonium assimilation, has been described. More recently, several studies have suggested a main role of G6PDH to counteract different stress conditions, among these salinity and drought, with the involvement of an ABA depending signal. In the last few years, this recognized vision has been greatly widened, due to studies clearly showing the non-conventional subcellular localization of the different G6PDHs, and the peculiar regulation of the different isoforms. The whole body of these considerations suggests a central question: how do the plant cells distribute the reductants coming from G6PDH and balance their equilibrium? This review explores the present knowledge about these mechanisms, in order to propose a scheme of distribution of reductants produced by G6PDH during nitrogen assimilation and stress. PMID- 27187491 TI - The recency ratio as an index of cognitive performance and decline in elderly individuals. AB - Individuals with Alzheimer's disease have been found to present a typical serial position curve in immediate recall tests, showing poor primacy performance and exaggerated recency recall. However, the recency advantage is usually lost after a delay. On this basis, we examined whether the recency ratio (Rr), calculated by dividing recency performance in an immediate memory task by recency performance in a delayed task, was a useful risk marker of cognitive decline. We tested whether change in Mini-Mental State Examination (MMSE) performance between baseline and follow-up was predicted by baseline Rr and found this to be the case (N = 245). From these analyses, we conclude that participants with high Rr scores, who show disproportionate recency recall in the immediate test compared to the delayed test, present signs of being at risk for cognitive decline or dysfunction. PMID- 27187492 TI - Cluster Plasmonics: Dielectric and Shape Effects on DNA-Stabilized Silver Clusters. AB - This work investigates the effects of dielectric environment and cluster shape on electronic excitations of fluorescent DNA-stabilized silver clusters, AgN-DNA. We first establish that the longitudinal plasmon wavelengths predicted by classical Mie-Gans (MG) theory agree with previous quantum calculations for excitation wavelengths of linear silver atom chains, even for clusters of just a few atoms. Application of MG theory to AgN-DNA with 400-850 nm cluster excitation wavelengths indicates that these clusters are characterized by a collective excitation process and suggests effective cluster thicknesses of ~2 silver atoms and aspect ratios of 1.5 to 5. To investigate sensitivity to the surrounding medium, we measure the wavelength shifts produced by addition of glycerol. These are smaller than reported for much larger gold nanoparticles but easily detectable due to narrower line widths, suggesting that AgN-DNA may have potential for fluorescence-reported changes in dielectric environment at length scales of ~1 nm. PMID- 27187490 TI - The Multifocal On- and Off-Responses in the Human Diabetic Retina. AB - The characteristics of the on- and off-responses in the human diabetic retina by a "long-duration" multifocal electroretinogram (mfERG) paradigm were investigated. Changes in the retinal antagonistic interaction were also evaluated in the early stage of diabetes mellitus (DM). Twenty type II diabetic patients with no or mild non-proliferative diabetic retinopathy (NPDR) and twenty-one age matched healthy controls were recruited for "long-duration" mfERG measurements. A 61-hexagon mfERG stimulus was displayed under two chromatic conditions (white/black and blue/black) at matched luminance. The amplitudes and implicit times of the on-response components (N1, P1 and N2) and off-response (P2) components were analysed. The blue stimulation generally triggered greater mfERG amplitudes in P1, N2 and P2 (p<0.05) than those from white stimulation in both control and diabetic groups. The diabetic group showed significantly greater N2 amplitude than the controls under white stimulation in mid-retinal regions (Rings 2 and 4) (p<0.05). When the stimulus was changed from white to blue, the diabetic group showed a smaller percentage change in N2 amplitude than the controls in peripheral retinal region (Ring 5) (p<0.02). When a stimulus is changed from white (broad-band spectral stimulation) to blue (narrow-band spectral stimulation), a decrease in the involvement of lateral antagonism would be expected. The larger amplitude of the on-response component (N2) in the diabetic patients suggested an imbalance of lateral antagonism, and the lesser percentage change of N2 amplitude in the diabetic group may indicate an impairment of the cross-talk at the middle retinal level in early stages of DM. PMID- 27187493 TI - Is the Hierarchy of Loss in Functional Ability Evident in Midlife? Findings from a British Birth Cohort. AB - BACKGROUND: Difficulties performing a range of physical tasks of daily living have been shown to develop in older populations in a typically observed sequence, known as the hierarchy of loss. Nearly all previous research has been undertaken using populations aged over 75. This study aimed to use cross-sectional and longitudinal data to test for evidence of the hierarchy of loss from midlife onwards. METHODS: The prevalence of reported difficulty undertaking 16 physical tasks in the MRC National Survey of Health and Development at age 60-64 were calculated, with Mokken scaling used to confirm the hierarchical order. Logistic regression was used to calculate the odds ratios of reporting difficulty performing tasks at the bottom of the hierarchy (i.e. feeding, washing and/or toileting) at age 60-64 by reported difficulty at the top of the hierarchy (i.e. gripping, walking and/or stair climbing) at age 43. RESULTS: At age 60-64, tasks associated with balance, strength and co-ordination, such as climbing stairs, were the first tasks participants reported difficulty with and tasks associated with upper limb mobility, such as feeding yourself, were the last. In a fully adjusted model, participants who reported difficulty at the top of the hierarchy at age 43 were 2.85 (95% CI: 1.45-5.60) times more likely to report difficulty with tasks at the bottom of the hierarchy at age 60-64. CONCLUSION: This study presents evidence of the hierarchy of loss in a younger population than previously observed suggesting that targeted interventions to prevent functional decline should not be delayed until old age. PMID- 27187495 TI - Effectiveness Modelling and Economic Evaluation of Primary HPV Screening for Cervical Cancer Prevention in New Zealand. AB - BACKGROUND: New Zealand (NZ) is considering transitioning from 3-yearly cervical cytology screening in women 20-69 years (current practice) to primary HPV screening. We evaluated HPV-based screening in both HPV-unvaccinated women and cohorts offered HPV vaccination in New Zealand (vaccination coverage ~50%). METHODS: A complex model of HPV transmission, vaccination, cervical screening, and invasive cervical cancer was extensively validated against national population-based datasets. Sixteen potential strategies for HPV screening were considered. RESULTS: Most primary HPV strategies were more effective than current practice, for both unvaccinated women and cohorts offered vaccination. The optimal strategy for both groups was 5-yearly HPV screening in women aged 25-69 years with partial genotyping for HPV 16/18 and referral to colposcopy, and cytological triage of other oncogenic types. This is predicted to reduce cervical cancer incidence and mortality by a further 12-16% and to save 4-13% annually in program costs (excluding overheads). The findings are sensitive to assumptions about future adherence to initiating screening at 25 years. CONCLUSION: Primary HPV screening with partial genotyping would be more effective and less costly than the current cytology-based screening program, in both unvaccinated women and cohorts offered vaccination. These findings have been considered in a review of cervical screening in NZ. PMID- 27187488 TI - The Diversity of Ribonuclease P: Protein and RNA Catalysts with Analogous Biological Functions. AB - Ribonuclease P (RNase P) is an essential endonuclease responsible for catalyzing 5' end maturation in precursor transfer RNAs. Since its discovery in the 1970s, RNase P enzymes have been identified and studied throughout the three domains of life. Interestingly, RNase P is either RNA-based, with a catalytic RNA subunit, or a protein-only (PRORP) enzyme with differential evolutionary distribution. The available structural data, including the active site data, provides insight into catalysis and substrate recognition. The hydrolytic and kinetic mechanisms of the two forms of RNase P enzymes are similar, yet features unique to the RNA-based and PRORP enzymes are consistent with different evolutionary origins. The various RNase P enzymes, in addition to their primary role in tRNA 5' maturation, catalyze cleavage of a variety of alternative substrates, indicating a diversification of RNase P function in vivo. The review concludes with a discussion of recent advances and interesting research directions in the field. PMID- 27187494 TI - Case-Only Survival Analysis Reveals Unique Effects of Genotype, Sex, and Coronary Disease Severity on Survivorship. AB - Survival bias may unduly impact genetic association with complex diseases; gene specific survival effects may further complicate such investigations. Coronary artery disease (CAD) is a complex phenotype for which little is understood about gene-specific survival effects; yet, such information can offer insight into refining genetic associations, improving replications, and can provide candidate genes for both mortality risk and improved survivorship in CAD. Building on our previous work, the purpose of this current study was to: evaluate LSAMP SNP specific hazards for all-cause mortality post-catheterization in a larger cohort of our CAD cases; and, perform additional replication in an independent dataset. We examined two LSAMP SNPs-rs1462845 and rs6788787-using CAD case-only Cox proportional hazards regression for additive genetic effects, censored on time-to all-cause mortality or last follow-up among Caucasian subjects from the Catheterization Genetics Study (CATHGEN; n = 2,224) and the Intermountain Heart Collaborative Study (IMHC; n = 3,008). Only after controlling for age, sex, body mass index, histories of smoking, type 2 diabetes, hyperlipidemia and hypertension (HR = 1.11, 95%CI = 1.01-1.22, p = 0.032), rs1462845 conferred significantly increased hazards of all-cause mortality among CAD cases. Even after controlling for multiple covariates, but in only the primary cohort, rs6788787 conferred significantly improved survival (HR = 0.80, 95% CI = 0.69 0.92, p = 0.002). Post-hoc analyses further stratifying by sex and disease severity revealed replicated effects for rs1462845: even after adjusting for aforementioned covariates and coronary interventional procedures, males with severe burden of CAD had significantly amplified hazards of death with the minor variant of rs1462845 in both cohorts (HR = 1.29, 95% CI = 1.08-1.55, p = 0.00456; replication HR = 1.25, 95% CI = 1.05-1.49, p = 0.013). Kaplan-Meier curves revealed unique cohort-specific genotype effects on survival. Additional analyses demonstrated that the homozygous risk genotype ('A/A') fully explained the increased hazard in both cohorts. None of the post-hoc analyses in control subjects were significant for any model. This suggests that genetic effects of rs1462845 on survival are unique to CAD presence. This represents formal, replicated evidence of genetic contribution of rs1462845 to increased risk for all-cause mortality; the contribution is unique to CAD case status and specific to males with severe burden of CAD. PMID- 27187496 TI - Braille in the Sighted: Teaching Tactile Reading to Sighted Adults. AB - Blind people are known to have superior perceptual abilities in their remaining senses. Several studies suggest that these enhancements are dependent on the specific experience of blind individuals, who use those remaining senses more than sighted subjects. In line with this view, sighted subjects, when trained, are able to significantly progress in relatively simple tactile tasks. However, the case of complex tactile tasks is less obvious, as some studies suggest that visual deprivation itself could confer large advantages in learning them. It remains unclear to what extent those complex skills, such as braille reading, can be learnt by sighted subjects. Here we enrolled twenty-nine sighted adults, mostly braille teachers and educators, in a 9-month braille reading course. At the beginning of the course, all subjects were naive in tactile braille reading. After the course, almost all were able to read whole braille words at a mean speed of 6 words-per-minute. Subjects with low tactile acuity did not differ significantly in braille reading speed from the rest of the group, indicating that low tactile acuity is not a limiting factor for learning braille, at least at this early stage of learning. Our study shows that most sighted adults can learn whole-word braille reading, given the right method and a considerable amount of motivation. The adult sensorimotor system can thus adapt, to some level, to very complex tactile tasks without visual deprivation. The pace of learning in our group was comparable to congenitally and early blind children learning braille in primary school, which suggests that the blind's mastery of complex tactile tasks can, to a large extent, be explained by experience dependent mechanisms. PMID- 27187498 TI - Current problems associated with the microbiological point-of-care testing of respiratory tract infections in primary care. PMID- 27187497 TI - Structure and Genetic Variability of the Oceanic Whitetip Shark, Carcharhinus longimanus, Determined Using Mitochondrial DNA. AB - Information regarding population structure and genetic connectivity is an important contribution when establishing conservation strategies to manage threatened species. The oceanic whitetip shark, Carcharhinus longimanus, is a highly migratory, large-bodied, pelagic shark listed by the IUCN (International Union for Conservation of Nature) Red List as "vulnerable" throughout its range and "critically endangered" in the western north Atlantic. In 2014, the species was protected globally under Appendix II of CITES (Convention on International Trade in Endangered Species), limiting and regulating trade. This study used partial sequences of mitochondrial DNA (mtDNA) control region to determine the population genetic structure of oceanic whitetip sharks across the Atlantic and Indian Oceans. 724 base pairs were obtained from 215 individuals that identifed nine polymorphic sites and defined 12 distinct haplotypes. Total nucleotide diversity (pi) was 0.0013 and haplotype diversity (h) was 0.5953. The Analysis of Molecular Variance (AMOVA) evidenced moderate levels of population structure (phiST = 0.1039) with restricted gene flow between the western and eastern Atlantic Ocean, and a strong relationship between the latter region and the Indian Ocean. Even though the oceanic whitetip is a highly migratory animal the results presented here show that their genetic variability is slightly below average of other pelagic sharks. Additionally, this study recommends that at least two populations in the Atlantic Ocean should be considered distinct (eastern and western Atlantic) and conservation efforts should be focused in areas with the greatest genetic diversity by environmental managers. PMID- 27187499 TI - A primary care-based asthma program improves recognition and treatment of persistent asthma in inner-city children compared to routine care. AB - OBJECTIVE: To examine whether a primary care-based asthma program that applies the Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma-2007 criteria to classify asthma severity increases detection of persistent asthma in inner-city children and affects "step of care" compared to routine care. METHODS: A retrospective chart review was conducted of 97 consecutive children referred to the asthma program from 2011-2013. Asthma severity documented during routine health care maintenance visits was compared to the asthma severity assessed during the asthma program visit using five standardized questions and spirometry. Medication plan "step of care" was compared pre- and post- the asthma program visit. RESULTS: 79 children, ages 5-19 years old (mean = 9.6), had spirometry tracings meeting American Thoracic Society criteria and were included in this study. 53% were male. The majority of children were Latino (45.6%) or African American (35.4%). At the asthma program visit, more children were identified with moderate or severe persistent asthma based upon clinical questions (47.9%), spirometry (56.9%) or combined criteria (75.3%) than had been identified during routine care (15.2%); all p < .05. After the asthma program visit, more children were prescribed controller medications (82.3% vs 63.3%; p < .05) and 40.6% had their medication plan stepped up. CONCLUSIONS: In this population of inner-city children, asthma severity was under-recognized and undertreated during routine care. A primary care based asthma program, which formalized applying EPR-3 criteria, increased detection of persistent asthma and led to "step-ups" in treatment plans. PMID- 27187500 TI - Don't Take It Personal: European Union Legal Aspects of Procuring and Protecting Environmental Exposure Data in Population Biobanks Through the Use of a Geo Information-Systems Toolkit. AB - Under European Union (EU) law, population-based cohort studies have the right to collect environmental data and to access geospatial data, at street level, on the web, from a host of public sources. As to geospatial information, they should be able to avail themselves of Member States' networks of services for geospatial data sets and services (discovery, viewing, downloading) via the Internet. On the other hand, linkage of health data of biobank participants to environmental data, using geospatial data, is limited, as it must satisfy the provisions of the EU Directive on the Protection of Personal Data, pursuant to which geospatial data regarding biobank participants are likely to qualify as personal data. Hence, we submit that the consents of biobank participants be reviewed to assess whether they cover the generation and linkage of geospatial data. We also submit that biobanks must have measures in place to prevent the re-identification of participants by use of their geospatial data. We present a model Geographic Information-Systems (GIS) Toolkit, as an example of what measures could be taken to that effect. PMID- 27187501 TI - Endoscopic ampullectomy: a technical review. AB - BACKGROUND AND AIM: This article provides a practical review to undertaking safe endoscopic ampullectomy and highlights some of the common difficulties with this technique as well as offering strategies to deal with these challenges. METHODS: We conducted a review of studies regarding endoscopic ampullectomy for ampullary neoplasms with special focus on techniques. RESULTS: Accurate preoperative diagnosis and staging of ampullary tumors is imperative for predicting prognosis and determining the most appropriate therapeutic approach. The optimal technique for endoscopic ampullectomy is dependent on the lesions size. En bloc resection is recommended for lesions confined to the papilla. There is no significant evidence to support the submucosal injection before ampullectomy. There is no consensus regarding the optimal current and power output for endoscopic ampulectomy. The benefits of a thermal adjunctive therapy remain controversial. A prophylactic pancreatic stent reduces the incidence and severity of pancreatitis post-ampullectomy. CONCLUSIONS: Endoscopic ampullectomy is a safe and efficacious therapeutic procedure for papillary adenomas in experienced endoscopist and it can avoid the need for surgical intervention. PMID- 27187504 TI - Residue level and dissipation pattern of lepimectin in shallots using high performance liquid chromatography coupled with photodiode array detection. AB - Lepimectin, as an emulsifiable concentrate, was sprayed on shallots at the recommended dose rate (10 mL/20 L) to determine its residue levels, dissipation pattern, pre-harvest residue limits (PHRLs), and health risk. Samples were randomly collected over 10 days, extracted with acetonitrile, purified using an amino solid-phase extraction (NH2 -SPE) cartridge and analyzed using a high performance liquid chromatography-photodiode array detection method. Field incurred samples were confirmed using ultra-performance liquid chromatography tandem mass spectrometry. The linearity was excellent, with a determination coefficient (R2 ) of >=0.9991. The recoveries at two spiking levels (0.2 and 1.0 mg/kg) ranged from 84.49 to 87.64% with relative standard deviations of <=7.04%. The developed method was applied to field samples grown in separate greenhouses, one located in Naju and one in Muan, in the Republic of Korea. The dissipation pattern was described by first-order kinetics with half-lives of 1.9 (Naju) and 1.7 days (Muan). The PHRL curves indicated that, if the lepimectin residues are <0.18 (Naju) and <0.13 mg/kg (Muan) 5 days before harvest, the residue levels will be lower than the maximum residue limit (0.05 mg/kg) upon harvesting. The risk assessment data indicated that lepimectin is safe for use in the cultivation of shallots, with no risk of detrimental effects to the consumer. PMID- 27187505 TI - Surfactant-assisted water exposed electrospinning of novel super hydrophilic polycaprolactone based fibers. AB - Hybrid scaffolds prepared by blend electrospinning of Polycaprolactone and Pluronic solution benefit from enhanced fiber hydrophilicity and may offer satisfactory cell attachment and proliferation. To improve hybrid scaffold wettability and water swelling ratio, adequate amount of hydrophilic polymer is required; though this amount is limited by fiber surface enrichment of Pluronic and cannot be exceeded without affecting the scaffold mechanical properties. To overcome this problem, a routine blend electrospinning setup was modified by exposing the blend solution to water in order to attract Pluronic chains toward the surface of the charged jet. Morphology of scaffolds produced by the routine blend electrospinning and modified method was studied. A 50 nm thick Pluronic layer with linty appearance on the surface of the fibers fabricated by the modified method was detected. Drug-loaded fibers from modified method showed a moderate initial burst and then a prolonged release period while an abnormal two stage phased release profile was observed for the routine blend method. The latter was associated to Pluronic/drug accumulations within the fibers fabricated by the routine method which resulted in fiber disintegration and a subsequent second burst release. PMID- 27187506 TI - Notes on the Psychoanalytic Significance of the Choice of Analyst. PMID- 27187507 TI - Further Notes on Choosing an Analyst. PMID- 27187508 TI - What Kind of Therapist for What Kind of Patient Who Has What Type of Problem? PMID- 27187509 TI - Appreciation of the Importance of the Patient-Analyst "Match". PMID- 27187510 TI - Conventional Wisdom in Psychiatry and Psychoanalysis. PMID- 27187511 TI - Why Do Some Therapies Succeed and Why Do Some Fail? PMID- 27187512 TI - Theory of Mind Impairments in Youth at Clinical High Risk of Psychosis. AB - OBJECTIVE: The normal maturational processes of theory of mind (ToM) capacity are ongoing during adolescence and even early adulthood. However, research has shown that ToM ability also declines among adults suffering from prodromal psychotic experiences. The goal of this study was to investigate the characteristics of ToM performance in youth with clinical high risk (CHR) of psychosis. METHODS: The Reading Mind in Eyes Task (RMET), including own-race and other-race eyes, was administered to 40 CHR youth; 42 age-, gender-, and education-matched healthy controls (HCs); and 62 adult patients with schizophrenia (SZ). Nine-month follow up data were collected from 31 CHR subjects, of whom 7 (22.6%) had made the transition to psychosis. RESULTS: CHR youth showed significant impairment in RMET performance compared to HC youth but performed better than did SZ patients. Moreover, they were significantly slower than were HC youth in responding to the RMET, with a response time similar to that of SZ patients. In particular, they had significantly poorer accuracy in interpreting positive and neutral eye expressions compared to the HC group, but not in interpreting negative eye expressions. Preliminary follow-up data showed a trend toward significance (p = 0.079) for RMET performance between those who transitioned to psychosis and those who did not. CONCLUSIONS: Our findings illustrate that deficits in ToM capacity, specifically the ability to interpret people's mental state from eye expressions, occur early on in prodromal psychosis in youth. Early interventions for CHR youth focusing on ToM enhancement may halt progress toward psychosis. PMID- 27187513 TI - A Pilot Study of Interpersonal Psychotherapy for PTSD in Women Veterans. AB - OBJECTIVE: This pilot study aimed to determine whether interpersonal psychotherapy (IPT) for posttraumatic stress disorder (PTSD) would be effective with a sample of women veterans who experienced military-related PTSD. METHOD: Women veterans presenting for mental health services through the Trauma Services Program at the Washington, DC, Veterans Affairs Medical Center (VAMC) were referred to the study by Veterans Affairs (VA) clinicians if they experienced trauma during their military service and scored > 35 on the PTSD Checklist Military Version. A total of 20 women completed a baseline assessment and were referred to treatment, the first trial of this treatment method with a veteran sample. Of the 15 women veterans who started treatment, 10 completed a trial of 12 individual sessions. Assessments were conducted posttreatment and at three months posttreatment follow-up. RESULTS: There was a significant decline in PTSD symptom severity from baseline to posttreatment, and these gains were maintained at three-month follow-up. Approximately one-third of the group no longer met full criteria for PTSD diagnosis, results that are comparable to studies of evidence based treatments for PTSD (prolonged exposure and cognitive processing therapy) in military samples. CONCLUSIONS: IPT, a non-trauma-focused intervention that aims to increase social support and improve interpersonal functioning, shows promise as another means of addressing PTSD in veterans. It should be tested in a larger sample to determine if IPT for PTSD might serve as an alternative for veterans who would prefer a non-trauma-focused intervention to address their difficulties. PMID- 27187515 TI - Adolescents on the Front Line: Exposure to Shelling Via Television and the Parental Role. AB - OBJECTIVES: Research suggests that exposure to traumatic content via television inadvertently increases posttraumatic stress symptoms (PTSS) as well as psychological distress, especially among adolescent viewers. The aim of the current study was to assess the effect of news consumption on PTSS and general distress among adolescents who live in a war area, as well as to examine the role of parents as intermediaries of news broadcasting. METHOD: A total of 65 adolescents who live in a war zone filled out the Child Post Traumatic Stress Reaction Index, the Brief Symptoms Inventory, and a scale measuring the level of real-life exposure, news broadcast consumption, and parents as intermediaries of news broadcasting. RESULTS: A main effect for real-life exposure on both PTSS and general distress was revealed. Interestingly, a three-way interaction between real-life exposure, television exposure, and parents as intermediators was found for general distress. Only under low real-life exposure did parents as intermediaries buffer the effect of television exposure on general distress. CONCLUSIONS: Parental intermediation of news broadcasting of traumatic events, especially in situations of continuous, real-life exposure, is essential. PMID- 27187514 TI - Posttraumatic Stress Disorder, Hostile Cognitions, and Aggression in Iraq/Afghanistan Era Veterans. AB - OBJECTIVE: Most veterans with posttraumatic stress disorder (PTSD) are not violent, yet research has demonstrated that there is a substantial minority who are at increased risk. This study tested hypotheses regarding hyperarousal symptoms and hostile cognitions (i.e., "hostility") as potential mechanisms of the association between PTSD and physical aggression in a longitudinal sample of Iraq/Afghanistan era veterans. METHOD: The sample included U.S. veterans between the ages of 18 and 70 who served in the military after September 11, 2001. At baseline, 301 veterans were evaluated for PTSD and completed self-report measures of hostility. At six-month follow-up 275 veterans and their family members or friends reported on the veterans' physical aggression over the preceding interval. Regression models were used to evaluate relationships among PTSD status, hyperarousal cluster symptoms, and hostility at baseline, and physical aggression at six months. Bootstrapping was used to test for the mediation of baseline PTSD and six-month aggression by hostility. RESULTS: PTSD significantly predicted physical aggression over six months, but hyperarousal cluster symptoms did not account for unique variance among the three clusters in the longitudinal model. Hostility partially mediated the association of PTSD at baseline and physical aggression at six months. CONCLUSIONS: Hostility may be a mechanism of the association of PTSD and physical aggression in veterans, suggesting the potential utility of targeting hostile cognitions in therapy for anger and aggression in veterans with PTSD. PMID- 27187519 TI - Romantic Bonds, Binds, and Ruptures: Couples on the Brink. PMID- 27187521 TI - Atomic Resolution for the Energy Derivatives on the Reaction Path. AB - Definite algorithms for calculation of the atomic contributions to the reaction force Fxi and the reaction force constant kxi (the first and the second derivatives of the energy over the reaction path step) are presented. The electronic part in the atomic and group contributions has been separated, and this opened the way to identification of the reactive molecule fragments on the consecutive stages of the reaction path. Properties have been studied for the two canonical test reactions: CO + HF -> HCOF and HONS -> ONSH. PMID- 27187520 TI - Open compared with laparoscopic complete mesocolic excision with central lymphadenectomy for colon cancer: a systematic review and meta-analysis. AB - AIM: Several studies report improved survival in colon cancer with use of extended lymphadenectomy techniques (ELTs), such as D3 lymphadenectomy or complete mesocolic excision. The noninferiority of laparoscopic versus open techniques has already been established in D2 resections. The aim of this study was to compare the safety and efficacy of open and laparoscopic approaches for ELTs in colon cancer. METHOD: Major databases, including PubMed, Scopus and the Cochrane library, were searched using defined inclusion and exclusion criteria, and relevant data were extracted. The Cochrane and Newcastle-Ottawa tools were used for critical appraisal and quality assessment. Meta-analysis with various subgroup analyses were undertaken, and clinical and statistical heterogeneity, along with publication bias, were also assessed. RESULTS: One randomized and seven case-control trials were included. All studies were found to be of low methodological quality with some external validity issues. There was no difference in short-term mortality [OR = 2.16 (95% CI: 0.73-6.41); P = 0.16], anastomotic leakage, ileus or deep-sited infection/abscess. There was a trend for longer operative time [weighted mean difference (WMD) = -30.88 (95% CI: -62.38 to 0.61); P = 0.05] and shorter length of hospital stay [WMD = 2.29 (95% CI: -0.39 to 4.98); P = 0.09] with the laparoscopic approach. Laparoscopic right hemicolectomy had a lower wound-infection rate [OR = 2.87 (95% CI: 1.38-5.98); P = 0.005] compared with the relevant open group. No statistically significant difference was found in overall survival [hazard ratio (HR) = 0.85 (95% CI: 0.69 1.06); P = 0.15], disease-free survival, local recurrence and distant metastases. CONCLUSION: Based on the current evidence, the laparoscopic technique appears to be at least as safe as the open technique when used in performing ELTs for colonic cancer, with similar morbidity and oncological outcomes. PMID- 27187522 TI - Lipids-based nanostructured lipid carriers (NLCs) for improved oral bioavailability of sirolimus. AB - The main purpose of this study was to improve the oral bioavailability of sirolimus (SRL), a poorly water-soluble immunosuppressant, by encapsulating into lipids-based nanostructured lipid carriers (NLCs). SRL-loaded NLCs (SRL-NLCs) were prepared by a high-pressure homogenization method with glycerol distearates (PRECIROL ATO-5) as the solid lipid, oleic acid as the liquid lipids, and Tween 80 as the emulsifier. The SRL-NLCs prepared under optimum conditions was spherical in shape with a mean particle size of about 108.3 nm and an entrapment efficiency of 99.81%. In vitro release of SRL-NLCs was very slow, about 2.15% at 12 h, while in vitro lipolysis test showed fast digestion of the NLCs within 1 h. Relative oral bioavailability of SRL-NLCs in Beagle dogs was 1.81-folds that of the commercial nanocrystalline sirolimus tablets Rapamune(r). In conclusion, the NLCs show potential to improve the oral bioavailability of SRL. PMID- 27187524 TI - Visible Light Induced Oxydifluoromethylation of Styrenes with Difluoromethyltriphenylphosphonium Bromide. AB - A convenient, visible light induced oxidifluoromethylation of styrenes was developed. This protocol employs the readily prepared difluoromethyltriphenylphosphonium bromide as the difluoromethylating reagent and alcohols/water as the nucleophiles, affording difluoromethyl(CF2H)-containing alcohols and ethers in moderate to excellent yields. PMID- 27187523 TI - Reliability of Computer-Assisted Breast Density Estimation: Comparison of Interactive Thresholding, Semiautomated, and Fully Automated Methods. AB - OBJECTIVE: The purpose of this study was to investigate the reliability of computer-assisted methods of estimating breast density. MATERIALS AND METHODS: Craniocaudal mammograms of 100 healthy subjects were collected from a screening mammography database. Three expert readers independently assessed mammographic breast density twice in a 1-month period using interactive thresholding and semiautomated methods. In addition, fully automated breast density estimation software was used to generate objective breast density estimates. The reliability of the computer-assisted breast density estimation was assessed in terms of concordance correlation coefficients, limits of agreement, systematic difference, and reader variability. RESULTS: Statistically significant systematic bias (paired t test, p < 0.01) and variability (4.75-10.91) were found within and between readers for both the interactive thresholding and the semiautomated methods. Using the semiautomated method significantly reduced the within-reader bias of one reader (p < 0.02) and the between-reader variability of all three readers (p < 0.05). The breast density estimates obtained with the fully automated method had excellent agreement with those of the reference standard (concordance correlation coefficient, 0.93) without a significant systematic difference. CONCLUSION: Reader-dependent variability and systematic bias exist in breast density estimates obtained with the interactive thresholding method, but they may be reduced in part by use of the semiautomated method. Assessing reader performance may be necessary for more reliable breast density estimation, especially for surveillance of breast density over time. The fully automated method has the potential to provide reliable breast density estimates nearly free from reader-dependent systematic bias and reader variability. PMID- 27187526 TI - Pre-analytical and analytical aspects of EDTA-plasma iron measurement. AB - It has been demonstrated that quantification of ethylenediaminetetraacetic acid (EDTA)-plasma iron could complement the already existing Athlete Biological Passport (ABP) variables and provide additional evidence for blood transfusion. Here, a fast preparation of a blood sample was proposed directly in the EDTA blood tube without performing an aliquoting step. In addition, correlations in paired serum and EDTA-plasma samples and storage stability were investigated. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 27187525 TI - pH effects on adsorption behavior and self-aggregation of dodecylamine at muscovite/aqueous interfaces. AB - In this work, molecular dynamics simulation was used to examine the effect of solution pH on the adsorption behavior and self-aggregation of dodecylamine hydrochloride (DDA) on the muscovite (0 0 1) surface. The properties of surfactants are assessed in terms of density profiles in the direction perpendicular to the muscovite surface. Results show that although DDA can adsorb at muscovite at all pH we discussed, the self-aggregation of DDA varies significantly at different pH values. At pH 10, a compact hydrophobic monolayer forms on the muscovite surface. At pH 3, hemi-micelle aggregated structure forms with several DDA cations far away from muscovite surface. At pH 12, it has been confirmed that adsorption of DDA neutral molecules occurs with only a few DDA molecules adsorbing on muscovite directly and acting as a bridge linking the rest DDA molecules, which exists nearby muscovite surface irregularly. Density profiles revealed that at pH 10, DDA cations play a dominant role in the interaction between DDA surfactants and muscovite. While DDA molecules have difficulty in forming a hydrogen bond with the oxygen atom on the muscovite surfaces, and they co-adsorb onto muscovite through the electrostatic interactions with muscovite and hydrophobic force with DDA cations. Therefore, the hydrophobization of muscovite in the presence of DDA are higher at pH 10 than that at pH 3 and pH 12. Our results indicate that molecular dynamics simulation can be a power tool in charactering adsorption behavior of surfactants onto mineral surfaces at different pH values. PMID- 27187528 TI - Evaluation and comparison of trace metal accumulation in different tissues of potential bioindicator organisms: Macrobenthic filter feeders Styela plicata, Sabella spallanzanii, and Mytilus galloprovincialis. AB - Trace metal concentrations were measured in different tissues of Sabella spallanzanii, Styela plicata, and Mytilus galloprovincialis collected in the Termini Imerese Harbor (Sicily, Italy) to evaluate the potential use of these species as bioindicators. Higher bioaccumulation factors (BAFs) were calculated in the tube of S. spallanzanii, except for As, which had a higher BAF in the branchial crown of the same species. Regarding the other species analyzed, higher BAFs were found in the digestive gland of M. galloprovincialis. An exception was Pb, which was significantly more concentrated in the branchial basket and tunic of S. plicata. The BAFs calculated in the present study show that all the species analyzed accumulate a certain amount of metals as a consequence of filter feeding mechanisms, and thus it was possible to assess the suitability of S. plicata, S. spallanzanii, and M. galloprovincialis as indicators of water quality. In particular, the tube of S. spallanzanii is an important compartment in terms of metal retention and is more suitable for the evaluation of contamination from trace elements. Environ Toxicol Chem 2016;35:3062-3070. (c) 2016 SETAC. PMID- 27187529 TI - Silver(I)-Catalyzed Addition of Phenols to Alkyne Cobalt Cluster Stabilized Carbocations. AB - A smooth catalytic method to use phenols as the nucleophilic partner in the Nicholas reaction has been developed. The method uses either Ag(I) or Au(I) catalysts with AgClO4 or AgBF4 as the most efficient catalysts tested. Neither additional additives nor cocatalysts were required and the formation of the corresponding phenol adducts occurred in excellent yields. The process has the single limitation of the inability of less nucleophilic phenols (4-nitrophenol) to generate the corresponding adducts. Additionally, the reaction is highly diastereoselective. DFT calculations allow a catalytic cycle to be proposed that involves trimetallic intermediates; the rate-determining step of the reaction is hydroxy-group elimination in a cobalt-silver trimetallic intermediate. PMID- 27187527 TI - Biological and physical controls in the Southern Ocean on past millennial-scale atmospheric CO2 changes. AB - Millennial-scale climate changes during the last glacial period and deglaciation were accompanied by rapid changes in atmospheric CO2 that remain unexplained. While the role of the Southern Ocean as a 'control valve' on ocean-atmosphere CO2 exchange has been emphasized, the exact nature of this role, in particular the relative contributions of physical (for example, ocean dynamics and air-sea gas exchange) versus biological processes (for example, export productivity), remains poorly constrained. Here we combine reconstructions of bottom-water [O2], export production and (14)C ventilation ages in the sub-Antarctic Atlantic, and show that atmospheric CO2 pulses during the last glacial- and deglacial periods were consistently accompanied by decreases in the biological export of carbon and increases in deep-ocean ventilation via southern-sourced water masses. These findings demonstrate how the Southern Ocean's 'organic carbon pump' has exerted a tight control on atmospheric CO2, and thus global climate, specifically via a synergy of both physical and biological processes. PMID- 27187530 TI - Ensembles of adaptive spatial filters increase BCI performance: an online evaluation. AB - OBJECTIVE: In electroencephalographic (EEG) data, signals from distinct sources within the brain are widely spread by volume conduction and superimposed such that sensors receive mixtures of a multitude of signals. This reduction of spatial information strongly hampers single-trial analysis of EEG data as, for example, required for brain-computer interfacing (BCI) when using features from spontaneous brain rhythms. Spatial filtering techniques are therefore greatly needed to extract meaningful information from EEG. Our goal is to show, in online operation, that common spatial pattern patches (CSPP) are valuable to counteract this problem. APPROACH: Even though the effect of spatial mixing can be encountered by spatial filters, there is a trade-off between performance and the requirement of calibration data. Laplacian derivations do not require calibration data at all, but their performance for single-trial classification is limited. Conversely, data-driven spatial filters, such as common spatial patterns (CSP), can lead to highly distinctive features; however they require a considerable amount of training data. Recently, we showed in an offline analysis that CSPP can establish a valuable compromise. In this paper, we confirm these results in an online BCI study. In order to demonstrate the paramount feature that CSPP requires little training data, we used them in an adaptive setting with 20 participants and focused on users who did not have success with previous BCI approaches. MAIN RESULTS: The results of the study show that CSPP adapts faster and thereby allows users to achieve better feedback within a shorter time than previous approaches performed with Laplacian derivations and CSP filters. The success of the experiment highlights that CSPP has the potential to further reduce BCI inefficiency. SIGNIFICANCE: CSPP are a valuable compromise between CSP and Laplacian filters. They allow users to attain better feedback within a shorter time and thus reduce BCI inefficiency to one-fourth in comparison to previous non-adaptive paradigms. PMID- 27187531 TI - Extracorporeal Membrane Oxygenation for Pediatric Respiratory Failure: Risk Factors Associated With Center Volume and Mortality. AB - OBJECTIVES: Recent analyses show higher mortality at low-volume centers providing extracorporeal membrane oxygenation. We sought to identify factors associated with center volume and mortality to explain survival differences and identify areas for improvement. DESIGN: Retrospective cohort study. SETTING: Patients admitted to children's hospitals in the Pediatric Health Information System database and supported with extracorporeal membrane oxygenation for respiratory failure from 2003 to 2014. PATIENTS: A total of 5,303 patients aged 0-18 years old met inclusion criteria: 3,349 neonates and 1,954 children. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Low center volume was defined as less than 20, medium 20-49, and large greater than or equal to 50 cases per year. Center volume was also assessed as a continuous integer. Among neonates, clinical factors including intraventricular hemorrhage (relative risk, 1.4; 95% CI, 1.24 1.56) and acute renal failure (relative risk, 1.38; 95% CI, 1.20-1.60) were more common at low-volume compared to larger centers and were associated with in hospital death. After adjustment for differences in demographic factors and primary pulmonary conditions, mild prematurity, acute renal failure, intraventricular hemorrhage, and receipt of dialysis remained independently associated with mortality, as did center volume measured as a continuous number. Among children, the risk of acute renal failure was almost 20% greater (relative risk, 1.18; 95% CI, 1.02-1.38) in small compared to large centers, but dialysis and bronchoscopy were used significantly less but were associated with mortality. After adjustment for differences in demographic factors and primary pulmonary conditions, acute renal failure, acute liver necrosis, acute pancreatitis, and receipt of bronchoscopy remained independently associated with mortality. Center volume measurement was not associated with mortality given these factors. CONCLUSIONS: Among neonates, investigation for intraventricular hemorrhage prior to extracorporeal membrane oxygenation and preservation of renal function are important factors for improvement. Earlier initiation of extracorporeal membrane oxygenation and careful attention to preservation of organ function are important to improve survival for children. PMID- 27187532 TI - Virtual Reality: The New Era of Rehabilitation Engineering [From the Regional Editor]. AB - Rehabilitation engineering refers to the development and application of techniques, devices, and protocols for restoring function following disability. Although in most cases the concept relates to motor functions (e.g., training after a stroke or the use of limb prosthetics), mental rehabilitation engineering is also an emerging area. PMID- 27187533 TI - New Prostheses and Orthoses Step Up their Game: Motorized Knees, Robotic Hands, and Exosuits Mark Advances in Rehabilitation Technology. AB - Forty years ago, Les Baugh lost both of his arms in an electrical accident. With bilateral shoulder-level amputations, his options for prosthetic arms were limited. That changed two years ago, when Baugh underwent a surgical procedure at Johns Hopkins Hospital in Baltimore that allowed him to control state-of-the-art robotic arms using nerves that had been rerouted to his chest. Within ten days of training, he was able to control both arms simultaneously and move a cup from a lower shelf to a higher shelf-a task that previously had been impossible-just by thinking about how he wanted to move his arm. PMID- 27187534 TI - The U.K. Pushes the Boundaries of Bionics: Researchers and Engineers Are Making Great Strides Toward Advanced Prosthetics' Ultimate Goal-Mimicking the Functionality of a Real Limb. AB - Using state-of-the-art technology, athletes at the Paralympic Games achieve great feats of physical prowess, but for most people using assistive and rehabilitative technologies (ART), even simple tasks can present huge challenges. Many do not make full use of the technology available to them because it is unreliable, uncomfortable, and nonintuitive, so researchers are pushing the envelope to create practical solutions that function like real limbs. PMID- 27187535 TI - Staying in Touch: Toward the Restoration of Sensory Feedback in Hand Prostheses Using Peripheral Neural Stimulation. AB - Hand amputation is a traumatic event that dramatically and permanently changes the life of any person who undergoes one. After surgery, the amputee requires a prosthetic device to perform activities of daily living-in particular, tasks requiring grasping and manipulation functions. According to the Washington, D.C. based Amputee Coalition, there are 1.9 million amputees who use limb prosthetic services and products, and it is estimated that, among them, 500,000 are upper limb amputees, with approximately 185,000 new amputations every year (www.amputee coalition.org). The Center for Orthotic and Prosthetic Care, a consortium of providers in Kentucky, Indiana, North Carolina, and New York, says that upper limb amputations represent 14% of all amputations (www.centeropcare.com). Based on these statistics, we can estimate that, in the European Union, there are a total of 3 million amputees, with 290,000 new cases each year; among these, 40,000 are upperlimb amputations. PMID- 27187536 TI - Taking on Essential Tremor: New Tools and Approaches Offer patients Increased Treatment Options. AB - Every year, Doris's primary care physician sends her to see a neurologist to check on her hand tremor, which has increasingly worsened over the past 20 years. Year in and year out, the neurologist asks her to draw a circle on a piece of paper. "The doctor looks at it, says 'Hmm,' and sends me home," Doris explains, adding that she gets no treatment, no recommendations, nothing except a request to schedule next year's appointment. PMID- 27187537 TI - A Better View: New Low-Vision Technology Helps Bring the World Into Focus. AB - Approximatley 2% of Americans have a visual disability-vision that cannot be corrected even with the strongest prescription-and in developing countries where infectious disease or untreated cataracts are more common, the percentage is often higher. Many different diseases and conditions can cause low vision, including age-related macular degeneration, diabetic retinopathy, and cone dystrophy (a genetic mutation affecting the cone cells of the retina). People with low vision find everyday activities more challenging. They may not be able to decipher small type, especially text on busy or colored backgrounds; see a plastic toy or other trip hazard left lying on the sidewalk; distinguish faces from more than a few feet away; or read street signs or the route number on a bus to help them get around town. PMID- 27187538 TI - The ?"Jaipur Foot?": India?s Most Popular Prosthetic for Amputees Is Not the Latest in Technology, but It's Still the Most Suitable Option for Many Patients Almost 50 Years after Its Development. AB - It is 8 a.m. on a December morning in Jaipur, Rajasthan, India. The day has just begun at Bhagawan Mahavir Vikalanga Sahayata Samithi (BMVSS), a nonprofit organization dedicated to fitting the disabled with artificial limbs (Figure 1). Slowly, patients from across India and neighboring countries gather in the center?s front yard. By the end of the day, more than 35 people will make a long journey back to their homes and communities outfitted with a new prosthetic leg or arm that will promise them a more active and functional future. The entire treatment is free. PMID- 27187539 TI - Pleasant to the Touch: By Emulating Nature, Scientists Hope to Find Innovative New Uses for Soft Robotics in Health-Care Technology. AB - Open your Internet browser and search for videos showing the most advanced humanoid robots. Look at how they move and walk. Observe their motion and their interaction with the environment (the ground, users, target objects). Now, search for a video of your favorite sports player. Despite the undoubtedly great achievements of modern robotics, it will become quite evident that a lot of work still remains. PMID- 27187540 TI - From Hospital to Home Care: Creating a Domotic Environment for Elderly and Disabled People. AB - Advances in medicine have led to a significant increase in human life expectancy and, therefore, to a growing number of disabled elderly people who need chronic care and assistance [1]. The World Health Organization reports that the world's population over 60 years old will double between 2000 and 2050 and quadruple for seniors older than 80 years, reaching 400 million [2]. In addition, strokes, traffic-related and other accidents, and seemingly endless wars and acts of terrorism contribute to an increasing number of disabled younger people. PMID- 27187541 TI - Giving Voice to Emotion: Voice Analysis Technology Uncovering Mental States is Playing a Growing Role in Medicine, Business, and Law Enforcement. AB - It's tough to imagine anything more frustrating than interacting with a call center. Generally, people don't reach out to call centers when they?re happy they're usually trying to get help with a problem or gearing up to do battle over a billing error. Add in an automatic phone tree, and you have a recipe for annoyance. But what if that robotic voice offering you a smorgasbord of numbered choices could tell that you were frustrated and then funnel you to an actual human being? This type of voice analysis technology exists, and it's just one example of the many ways that computers can use your voice to extract information about your mental and emotional state-including information you may not think of as being accessible through your voice alone. PMID- 27187542 TI - Metabolism: The Physiological Power-Generating Process: A History of Methods to Test Human Beings' ?"Vital Capacity?" [Retrospectroscope]. AB - A previous "Retrospectroscope" note, published early in 2014, dealt with spirometry: it described many apparatuses used to measure the volume of inhaled and exhaled air that results from breathing [1]. Such machines, when adequately modified, are also able to measure the rate at which work is produced (specifically by an animal or a human being). Metabolism in that sense is the term used by physiologists and physicians, a word that in Greek, metabolismos, means "change" or "overthrow," in the sense of breaking down material, as in burning some stuff. PMID- 27187544 TI - Hydrogel Adhesion with Wrinkle Formation by Spatial Control of Polymer Networks. AB - We prepared a novel wrinkled adhesive interface of hydrogels for strong adhesion via spatial control of polymer networks, including the density, distribution, and mobility of interactive units. A wrinkle structure was formed by the elasticity mismatch of hydrogels and adhesive polyion complex layers when electrophoresis was carried out between cationic and anionic semi-IPNs. The wrinkling wavelength of interfaces was controlled by Young's modulus of hydrogels. The role of wrinkle structure in adhesion was investigated by the measurement of the adhesive strength of hydrogels which were adhered under the compression, resulting in the disappearance of the wrinkle structure by compression that induced a decrease in adhesive strength. These results indicate that strong hydrogel adhesion was achieved by both the spatial design of interactive units and wrinkle formation. PMID- 27187543 TI - Heavy Alcohol Use Among Suicide Decedents Relative to a Nonsuicide Comparison Group: Gender-Specific Effects of Economic Contraction. AB - BACKGROUND: The primary objective of this gender-stratified study was to assess the rate of heavy alcohol use among suicide decedents relative to a nonsuicide comparison group during the 2008 to 2009 economic crisis. METHODS: The National Violent Death Reporting System and the Behavioral Risk Factor Surveillance System were analyzed by gender-stratified multiple logistic regression to test whether change in acute intoxication (blood alcohol content >=0.08 g/dl) before (2005 to 2007), during (2008 to 2009), and after (2010 to 2011) the Great Recession mirrored change in heavy alcohol use in a living sample. RESULTS: Among men, suicide decedents experienced a significantly greater increase (+8%) in heavy alcohol use at the onset of the recession (adjusted ratio of odds ratio = 1.15, 95% confidence interval = 1.10 to 1.20) (relative to the prerecession period) than did men in a nonsuicide comparison group (-2%). Among women, changes in rates of heavy alcohol use were similar in the suicide and nonsuicide comparison groups at the onset and after the recession. CONCLUSIONS: Acute alcohol use contributed to suicide among men during the recent economic downturn. Among women who died by suicide, acute alcohol use mirrored consumption in the general population. Women may show resilience (or men, vulnerability) to deleterious interaction of alcohol with financial distress. PMID- 27187545 TI - Bridging Mechanistic and Phenomenological Models of Complex Biological Systems. AB - The inherent complexity of biological systems gives rise to complicated mechanistic models with a large number of parameters. On the other hand, the collective behavior of these systems can often be characterized by a relatively small number of phenomenological parameters. We use the Manifold Boundary Approximation Method (MBAM) as a tool for deriving simple phenomenological models from complicated mechanistic models. The resulting models are not black boxes, but remain expressed in terms of the microscopic parameters. In this way, we explicitly connect the macroscopic and microscopic descriptions, characterize the equivalence class of distinct systems exhibiting the same range of collective behavior, and identify the combinations of components that function as tunable control knobs for the behavior. We demonstrate the procedure for adaptation behavior exhibited by the EGFR pathway. From a 48 parameter mechanistic model, the system can be effectively described by a single adaptation parameter tau characterizing the ratio of time scales for the initial response and recovery time of the system which can in turn be expressed as a combination of microscopic reaction rates, Michaelis-Menten constants, and biochemical concentrations. The situation is not unlike modeling in physics in which microscopically complex processes can often be renormalized into simple phenomenological models with only a few effective parameters. The proposed method additionally provides a mechanistic explanation for non-universal features of the behavior. PMID- 27187546 TI - Importance and usage of the CHA2DS2-VASc score in predicting acute stent thrombosis. AB - OBJECTIVE: The CHA2DS2-VASc score is used to estimate thromboembolic risk in atrial fibrillation (AF). Its usefulness in predicting outcome in patients after a percutaneous coronary intervention is unknown. We aimed to evaluate the predictive value of the CHA2DS2-VASc score in AF-free patients who have undergone stent implantation. DESIGN: Patients were evaluated retrospectively. Among the 1371 patients, 38 presented with acute stent thrombosis (ST) and were included in the study. The CHA2DS2-VASc score was calculated before percutaneous coronary intervention and the association between the score and stent thrombosis was investigated. RESULTS: The patients were grouped into ST (+) and ST (-). The average CHA2DS2-VASc score for the ST (+) group was 3.79, whereas that for the ST (-) group was 2.16 (P<0.001). A direct correlation was observed between CHA2DS2 VASc scores and the rate of ST. When patients with a CHA2DS2-VASc score of greater than 2 were compared with those with a CHA2DS2-VASc score of up to 2, the higher score had a higher frequency of ST (P<0.001) and multivariate analysis identified the CHA2DS2-VASc score as an independent predictor of acute ST. CONCLUSION: A CHA2DS2-VASc score of greater than 2 was found to be an independent predictor for incidence of ST. The role of the CHA2DS2-VASc score in predicting ST has not been investigated earlier in an AF-free population and our study is the first to explore this aspect. PMID- 27187559 TI - Graphene functionalized with poly(vinyl alcohol) as a Pickering stabilizer for suspension polymerization of poly(methyl methacrylate). AB - Two types of thermally reduced graphenes (TRGs) having different lateral sizes were non-covalently modified with poly(vinyl alcohol) to endow water dispersibility. The modified TRGs were examined as Pickering stabilizers for the suspension polymerization of methyl methacrylate (MMA). They were effective graphene-based Pickering stabilizers for the system with almost all of the polymerized composite microparticles having a regular spherical shape. The particle size of the composite microparticles was tunable by the size or the amount of modified TRG used as stabilizer. The almost perfect core-shell structure of the composite microparticles effectively enhanced the thermal stability of the core PMMA. In addition, when the core-shell microparticles were compression molded into a monolith, the obtained composite exhibited an ultra-low percolation threshold of electrical conductivity of around 0.04vol%. PMID- 27187560 TI - Hydroxyurea and Pain History in Relation to Patient-Reported Outcomes Using PROMIS Measures and the Frequency of Assessments in Sickle Cell Disease Patients. PMID- 27187561 TI - Association Between Weight Gain and Remission Status at 3 Months in First-Episode Schizophrenia. PMID- 27187562 TI - Haemochromatosis: unexplained metacarpophalangeal or ankle arthropathy should prompt diagnostic tests: findings from two UK observational cohort studies. AB - OBJECTIVES: To examine demographic and clinical features leading to the diagnosis of hereditary haemochromatosis and assess factors that might enhance earlier diagnosis, with particular attention to arthritic symptoms. METHOD: Diagnostic features were captured directly from patients with haemochromatosis attending a specialist rheumatology clinic (group 1) and from analysis of a specifically designed questionnaire circulated to members of the UK Haemochromatosis Society (group 2). RESULTS: In groups 1 (n = 62) and 2 (n = 470), respectively, the diagnosis of haemochromatosis was made at a mean age of 52.8 and 56.4 years with 77% and 76% reporting joint symptoms with a mean duration of 8.3 and 8.1 years. The first joints to be affected in group 1 were the metacarpophalangeal (MCP; 38.5%) and ankle (29.5%) followed by the knee, hip, and proximal interphalangeal (PIP) joints. At the time of clinical assessment or questionnaire completion, the most prevalent regions with arthropathy in group 1 were PIP (64.5%), knee (64%), ankle (61%), and MCP (60%) and in group 2 the most prevalent joint regions self reported were the first carpometacarpal (CMC; 59%), wrist (52%), PIP (47%), MCP (46%), knee (42%), and ankle (35%). CONCLUSIONS: Data from both cohorts confirm the high prevalence of joint symptoms in haemochromatosis predating the diagnosis by many years. Discriminatory features of the arthropathy include the involvement of MCP joints and ankles at a relatively young age in the absence of trauma, all of which are unusual features of primary osteoarthritis (OA). The finding of this presentation should prompt diagnostic tests for haemochromatosis. PMID- 27187564 TI - Erratum: Double-barreled and Concentric Microelectrodes for Measurement of Extracellular Ion Signals in Brain Tissue. AB - An author's middle initial was omitted from the publication, Double-barreled and Concentric Microelectrodes for Measurement of Extracellular Ion Signals in Brain Tissue. The author's name has been updated to: Christine R. Rose from: Christine Rose. PMID- 27187563 TI - Occupational exposure and risk of chronic obstructive pulmonary disease: a systematic review and meta-analysis. AB - INTRODUCTION: Due to contradictory literature we have performed a systematic review and meta-analyse of population-based studies that have used Job Exposure Matrices to assess occupational exposure and risk of Chronic Obstructive Pulmonary Disease (COPD). AREAS COVERED: Two researchers independently searched databases for published articles using predefined inclusion criteria. Study quality was assessed, and results pooled for COPD and chronic bronchitis for exposure to biological dust, mineral dust, and gases/fumes using a fixed and random effect model. Five studies met predetermined inclusion criteria. The meta analysis showed low exposure to mineral dust, and high exposure to gases/fumes were associated with an increased risk of COPD. We also found significantly increased the risk of chronic bronchitis for low and high exposure to biological dust and mineral dust. Expert commentary: The relationship between occupational exposure assessed by the JEM and the risk of COPD and chronic bronchitis shows significant association with occupational exposure. However, the heterogeneity of the meta-analyses suggests more wide population-based studies with older age groups and longitudinal phenotype assessment of COPD to clarify the role of occupational exposure to COPD risk. PMID- 27187565 TI - At the mercy of viruses. AB - Viruses are responsible for many of the adaptive mutations in the human genome. PMID- 27187566 TI - Effects of autohydrolysis of Eucalyptus urograndis and Eucalyptus grandis on influence of chemical components and crystallinity index. AB - Samples of Eucalyptus urograndis and Eucalyptus grandis sawdust were autohydrolyzed in aqueous conditions to reach temperatures in the range 110-190 degrees C and reaction times of 0-150min in a minireactor. In each minireactor were used a liquor:wood ratio (10:1 L:kg dry wood), in order to assess the effects of the autohydrolysis severity and the crystalline properties of cellulose. The content of extractives, lignin, holocellulose, cellulose, hemicelluloses and crystallinity index obtained from the solid fraction after autohydrolysis of sawdust were determined. This study demonstrated that the hemicelluloses were extensively removed at 170 and 190 degrees C, whereas cellulose was partly degraded to Eucalyptus urograndis and Eucalyptus grandis sawdust. The lignin content decreased, while the extractives content increased. It was defined that during autohydrolysis, had a slight decreased on crystalline structure of cellulose of Eucalyptus urogandis and Eucalyptus grandis. PMID- 27187567 TI - A novel self-adaptive microalgae photobioreactor using anion exchange membranes for continuous supply of nutrients. AB - A novel self-adaptive microalgae photobioreactor using anion exchange membranes (AEM-PBR) for continuous supply of nutrients was proposed to improve microalgae biomass production. The introduction of anion exchange membranes to the PBR can realize continuous supply of nutrients at desired rates, which is beneficial to the growth of microalgae. The results showed that the maximum biomass concentration obtained in the AEM-PBR under continuous supply of nitrogen at an average rate of 19.0mgN/L/d was 2.98g/L, which was 129.2% higher than that (1.30g/L) in a PBR with all the nitrogen supplied in batch at initial. In addition, the feeding rates of nitrogen and phosphorus were optimized in the AEM PBR to maximize biomass production. The maximum biomass concentration of 4.38g/L was obtained under synergistic regulation of nitrogen and phosphorus feeding rates at 19.0mgN/L/d and 4.2mgP/L/d. The AEM-PBR demonstrates a promising approach for high-density cultivation of microalgae. PMID- 27187568 TI - Influence of pH on hydrothermal treatment of swine manure: Impact on extraction of nitrogen and phosphorus in process water. AB - This study investigates the influence of pH on extraction of nitrogen and phosphorus from swine manure following hydrothermal treatment. Conditions include thermal hydrolysis (TH) at 120 degrees C and 170 degrees C, and hydrothermal carbonisation (HTC) at 200 degrees C and 250 degrees C in either water alone or in the presence of 0.1M NaOH, H2SO4, CH3COOH or HCOOH. Phosphorus extraction is pH and temperature dependent and is enhanced under acidic conditions. The highest level of phosphorus is extracted using H2SO4 reaching 94% at 170 degrees C. The phosphorus is largely retained in the residue for all other conditions. The extraction of nitrogen is not as significantly influenced by pH, although the maximum N extraction is achieved using H2SO4. A significant level of organic-N is extracted into the process waters following hydrothermal treatment. The results indicate that operating hydrothermal treatment in the presence of acidic additives has benefits in terms of improving the extraction of phosphorus and nitrogen. PMID- 27187569 TI - Effects of DO levels on surface force, cell membrane properties and microbial community dynamics of activated sludge. AB - In this paper, we employ atomic force microscopy (AFM), fluorescence recovery after photobleaching (FRAP) technique, phospholipid fatty acids (PLFA) and MiSeq analysis to study the effects of traditional dissolved oxygen (DO) levels (0.71 1.32mg/L, 2.13-3.02mg/L and 4.31-5.16mg/L) on surface force, cell membrane properties and microbial community dynamics of activated sludge. Results showed that low DO level enhanced the surface force and roughness of activated sludge; the medium DO level decreased cell membrane fluidity by reducing the synthesis of branched fatty acids in the cell membrane; high DO level resulted in the highest protein content in the effluent by EEM scanning. Abundance of Micropruina, Zoogloea and Nakamurella increased and Paracoccus and Rudaea decreased with the increase of DO levels. RDA analysis suggested that saturated fatty acids (SFA), anteiso-fatty acids (AFA) and iso-fatty acids (IFA) were closely related to effluent quality as well as some genera. PMID- 27187571 TI - Spatial segregation of heterochromatin: Uncovering functionality in a multicellular organism. AB - Multiple layers of regulation are required to ensure appropriate patterns of gene expression for accurate cell differentiation. Interphase chromatin is non randomly distributed within the nucleus, with highly compacted, transcriptionally silent heterochromatin enriched at the nuclear and nucleolar periphery. Whether this spatial organization serves a function in organismal physiology, rather than simply being a byproduct of chromatin metabolism, is a fundamental question. Recent work performed in C. elegans embryos characterized the molecular mechanisms that drive the perinuclear anchoring of heterochromatin. Moreover, for the first time it was shown that heterochromatin sequestration helps to restrict cell differentiation programs, while sustaining commitment to a specified fate. Here, we describe and comment on these findings, placing them in a broader context. PMID- 27187573 TI - Progressively growing plaque on the neck of a healthy patient. PMID- 27187572 TI - How Membrane-Active Peptides Get into Lipid Membranes. AB - The structure-function relationship for a family of antimicrobial peptides (AMPs) from the skin of Australian tree frogs is discussed and compared with that of peptide toxins from bee and Australian scorpion venoms. Although these membrane active peptides induce a similar cellular fate by disrupting the lipid bilayer integrity, their lytic activity is achieved via different modes of action, which are investigated in relation to amino acid sequence, secondary structure, and membrane lipid composition. In order to better understand what structural features govern the interaction between peptides and lipid membranes, cell penetrating peptides (CPPs), which translocate through the membrane without compromising its integrity, are also discussed. AMPs possess membrane lytic activities that are naturally designed to target the cellular membrane of pathogens or competitors. They are extremely diverse in amino acid composition and often show specificity against a particular strain of microbe. Since our antibiotic arsenal is declining precariously in the face of the rise in multiantibiotic resistance, AMPs increasingly are seen as a promising alternative. In an effort to understand their molecular mechanism, biophysical studies of a myriad of AMPs have been reported, yet no unifying mechanism has emerged, rendering difficult the rational design of drug leads. Similarly, a wide variety of cytotoxic peptides are found in venoms, the best known being melittin, yet again, predicting their activity based on a particular amino acid composition or secondary structure remains elusive. A common feature of these membrane-active peptides is their preference for the lipid environment. Indeed, they are mainly unstructured in solution and, in the presence of lipid membranes, quickly adsorb onto the surface, change their secondary structure, eventually insert into the hydrophobic core of the membrane bilayer, and finally disrupt the bilayer integrity. These steps define the molecular mechanism by which these membrane active peptides lyse membranes. The last class of membrane-active peptides discussed are the CPPs, which translocate across the lipid bilayer without inducing severe disruption and have potential as drug vehicles. CPPs are typically highly charged and can show antimicrobial activity by targeting an intracellular target rather than via a direct membrane lytic mechanism. A critical aspect in the structure-function relationship of membrane-active peptides is their specific activity relative to the lipid membrane composition of the cell target. Cell membranes have a wide diversity of lipids, and those of eukaryotic and prokaryotic species differ greatly in composition and structure. The activity of AMPs from Australian tree frogs, toxins, and CPPs has been investigated within various lipid systems to assess whether a relationship between peptide and membrane composition could be identified. NMR spectroscopy techniques are being used to gain atomistic details of how these membrane-active peptides interact with model membranes and cells, and in particular, competitive assays demonstrate the difference between affinity and activity for a specific lipid environment. Overall, the interactions between these relatively small sized peptides and various lipid bilayers give insight into how these peptides function at the membrane interface. PMID- 27187574 TI - Inflating Strategy To Form Ultrathin Hollow MnO2 Nanoballoons. AB - Ultrathin MnO2 hollow nanoballoons (UMHNBs) have a large ratio of interfacial to total atoms, corresponding to expected improved performance. However, their synthesis is a challenge due to difficulty in controlling the concentration of the unit cells. Herein, we describe a strategy to synthesize dry intact UMHNBs through a one-step synthesis by inflating MnO2 (reduced from KMnO4) with CO2 (oxidized from single-layer graphene oxide nanosheets) followed by instant freeze drying. UMHNBs are 30-500 nm in diameter with a shell thickness of 3.7 nm, packing with laminar [MnO6] unit cells in the form of delta-MnO2. UMHNBs show efficient catalytic activity for decomposing the organic dye methylene blue (MB), 15 times the biggest reported value, and have long-term catalytic efficacy and durability. The described strategy in this paper makes use of graphene nanosheets to assemble durable ultrathin hollow nanoballoons. PMID- 27187575 TI - Role of inflammatory marker YKL-40 in the diagnosis, prognosis and cause of cardiovascular and liver diseases. AB - This review summarizes present evidence for the role of YKL-40 in the diagnosis, prognosis and cause of cardiovascular and alcoholic liver disease. The question of whether YKL-40 is merely a marker or a causal factor in the development of cardiovascular and liver disease is addressed, with emphasis on the Mendelian randomization design. The Mendelian randomization approach uses genetic variants associated with lifelong high plasma YKL-40 levels that are largely unconfounded and not prone to reverse causation. Thus, the approach mimics a controlled double blind randomized trial, but it uses genetic variants rather than a drug and placebo, and like a blinded trial, it allows inference about causality. Moreover, the review also covers background on the molecular biology and functions of YKL 40, YKL-40 levels in healthy individuals and reference range, and the role of YKL 40 as a biomarker of cardiovascular and alcoholic liver disease. YKL-40 is a plasma protein named after its three N-terminal amino acids, Y (tyrosine), K (lysine) and L (leucine), and its molecular weight of 40 kDa. It is produced by local inflammatory cells in inflamed tissues, such as lipid-laden macrophages inside the vessel wall and perhaps also hepatic stellate cells. Observational studies show that plasma YKL-40 levels are elevated in patients with cardiovascular and liver disease and are associated with disease severity and prognosis. Furthermore, elevated plasma YKL-40 levels in apparently healthy individuals are associated with a 2-fold increased risk of future ischemic stroke and venous thromboembolism, but not with myocardial infarction, suggesting that YKL-40 could play a role in the formation of embolisms rather than atherosclerosis per se. Further, elevated YKL-40 levels combined with excessive alcohol consumption are associated with 10-years risk of alcoholic liver cirrhosis of up to 7%, suggesting that YKL-40 can be used as a strong noninvasive marker of predicting alcoholic liver cirrhosis. Importantly, in Mendelian randomization studies, genetically elevated plasma YKL-40 levels were not associated with risk of cardiovascular and alcoholic liver disease, thus suggesting that plasma YKL-40 does not play a causal role in the development of these diseases. Despite this, plasma YKL-40 levels may play a role in disease progression after diagnosis, and inhibition of YKL-40 activity might be a novel therapy in some cardiovascular and liver diseases. PMID- 27187576 TI - Identification and Rating of Gynecologic Oncology Applications Using the APPLICATIONS Scoring System. AB - BACKGROUND: Currently, there are thousands of medical applications (apps) on the market potentially leading to app overload. Finding useful and accurate apps may be time-consuming and frustrating to gynecologic oncologists. INTRODUCTION: The objective of this study is to identify and rate gynecologic oncology (gyn-onc) apps using the APPLICATIONS scoring system. MATERIALS AND METHODS: A list of nonconsumer gyn-onc apps was identified from the Apple iTunes and Google Play Stores. Based on reliable references, inaccurate apps were excluded. The remaining apps were rated with the APPLICATIONS scoring system, which uses both objective and subjective measures. RESULTS: Of 748 apps identified, 11 (1.5%) were found to be both useful and accurate to gyn-onc providers. The apps with the lowest scores were calculator apps, while those with the highest scores were informational apps. DISCUSSION: We found useful and accurate calculator, screening, staging, and informational apps. However, a large number of the apps found were considered inaccurate or non-gyn-onc specific. CONCLUSIONS: Our systematic method for identifying and rating apps with the APPLICATIONS scoring system can be applied within other subspecialties of obstetrics and gynecology and other specialties of medicine to offer providers with apps in clinical care. PMID- 27187577 TI - Octopaminergic system in the central nervous system of the terrestrial slug Limax. AB - The terrestrial slug Limax can learn to avoid the odor of some food (e.g., carrot juice) by the simultaneous presentation of an aversive stimulus (e.g., bitterness of quinidine). This type of associative memory critically depends on the higher olfactory center, the procerebrum in the central nervous system. The modulation of the local field potential (LFP) oscillation recorded on the procerebrum has been thought to reflect the information processing of the odor that elicits the behavioral change, such as avoidance of the aversively learned odor or approaching an attractive food's odor. Here we focused on octopamine, an important neuromodulator involved in learning and memory in invertebrates, and considered to be the invertebrate equivalent of noradrenaline. We identified a few octopaminergic neurons in the subesophageal and buccal ganglia, and a larger number near the procerebrum in the cerebral ganglia, using immunohistochmical staining and in situ hybridization of tyramine beta-hydroxylase, an octopamine synthesizing enzyme. Application of octopamine reduced the frequency of LFP oscillation in a dose-dependent manner, and this effect was inhibited by preincubation with phentolamine. High-performance liquid chromatography analysis revealed the presence of octopamine, noradrenaline, and adrenaline in the central nervous system. Unexpectedly, noradrenaline and adrenaline both accelerated the LFP oscillation, in contrast to octopamine. Our results suggest that octopamine and noradrenaline have distinct functions in olfactory information processing, in spite of their structural similarity. J. Comp. Neurol. 524:3849-3864, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27187579 TI - Enhanced Air Stability in REPb3 (RE = Rare Earths) by Dimensional Reduction Mediated Valence Transition. AB - We conceptually selected the compounds REPb3 (RE = Eu, Yb), which are unstable in air, and converted them to the stable materials in ambient conditions by the chemical processes of "nanoparticle formation" and "dimensional reduction". The nanoparticles and the bulk counterparts were synthesized by the solvothermal and high-frequency induction furnace heating methods, respectively. The reduction of the particle size led to the valence transition of the rare earth atom, which was monitored through magnetic susceptibility and X-ray absorption near edge spectroscopy (XANES) measurements. The stability was checked by X-ray diffraction and thermogravimetric analysis over a period of seven months in oxygen and argon atmospheres and confirmed by XANES. The nanoparticles showed outstanding stability toward aerial oxidation over a period of seven months compared to the bulk counterpart, as the latter one is more prone to the oxidation within a few days. PMID- 27187578 TI - Functional Hyperbranched Polylysine as Potential Contrast Agent Probes for Magnetic Resonance Imaging. AB - Researchers have never stopped questing contrast agents with high resolution and safety to overcome the drawbacks of small-molecule contrast agents in clinic. Herein, we reported the synthesis of gadolinium-based hyperbranched polylysine (HBPLL-DTPA-Gd), which was prepared by thermal polymerization of l-lysine via one step polycondensation. After conjugating with folic acid, its potential application as MRI contrast agent was then evaluated. This contrast agent had no obvious cytotoxicity as verified by WST assay and H&E analysis. Compared to Gd(III)-diethylenetriaminepentaacetic acid (Gd-DTPA) (r1 = 4.3 mM(-1) s(-1)), the FA-HBPLL-DTPA-Gd exhibited much higher longitudinal relaxivity value (r1 = 13.44 mM(-1) s(-1)), up to 3 times higher than Gd-DTPA. The FA-HBPLL-DTPA-Gd showed significant signal intensity enhancement in the tumor region at various time points and provided a long time window for MR examination. The results illustrate that FA-HBPLL-DTPA-Gd will be a potential candidate for tumor-targeted MRI. PMID- 27187581 TI - Use of BODIPY-Cholesterol (TF-Chol) for Visualizing Lysosomal Cholesterol Accumulation. AB - Dipyrromethene difluoride-cholesterol (TopFluor-Cholesterol, TF-Chol) is a widely used cholesterol analogue due to its excellent fluorescence properties and considerable similarity with natural cholesterol in terms of membrane partitioning. However, the suitability of TF-Chol for detecting lysosomal cholesterol deposition has recently been questioned. Here, we highlight the fact that the method of lipid delivery and the analysis of time-point both affect the membrane distribution and labeling pattern of TF-Chol, similarly as with radiolabeled cholesterol. Lysosomal sterol accumulation characteristic to a lysosomal storage disease is most readily detected when the probe is introduced via the physiological route, i.e. as a sterol fatty acid ester in low-density lipoprotein particles. When administered to cells from solvent, lysosomal sterol sequestration becomes evident after an overnight equilibration between membranes. PMID- 27187580 TI - Anti-TGF-beta Antibody, 1D11, Ameliorates Glomerular Fibrosis in Mouse Models after the Onset of Proteinuria. AB - Fibrosis is a final common pathway leading to loss of kidney function, in which the fibrogenic cytokine, transforming growth factor beta (TGF-beta), plays a central role. While previous studies showed that TGF-beta antagonism by various means prevents fibrosis in mouse models, clinical approaches based on these findings remain elusive. 1D11 is a neutralizing antibody to all three isoforms of TGF-beta. In both adriamycin (ADR)-induced nephropathy and NEP25 podocyte ablation nephropathy, thrice-weekly intraperitoneal administration of 1D11 from the day of disease induction until the mice were sacrificed (day 14 for ADR and day 28 for NEP25), significantly reduced glomerular COL1A2 mRNA accumulation and histological changes. Consistent with our previous findings, proteinuria remained overt in the mice treated with 1D11, suggesting distinct mechanisms for proteinuria and fibrogenesis. Podocyte numbers determined by WT1 staining were significantly reduced in NEP25-model glomeruli as expected, while WT1-positive cells were preserved in mice receiving 1D11. Even when 1D11 was administered after the onset of proteinuria on day 3, 1D11 preserved WT1-positive cell numbers in glomeruli and significantly reduced glomerular scar score (2.5 +/- 0.2 [control IgG] vs. 1.8 +/- 0.2 [1D11], P < 0.05) and glomerular COL1A2 mRNA expression (19.3 +/- 4.4 [control IgG] vs. 8.4 +/- 2.4 [1D11] fold increase over the healthy control, P < 0.05). Transmission electron microscopy revealed loss of podocytes and denuded glomerular basement membrane in NEP25 mice with disease, whereas podocytes remained attached to the basement membrane, though effaced and swollen, in those receiving 1D11 from day 3. Together, these data suggest that TGF-beta neutralization by 1D11 prevents glomerular fibrosis even when started after the onset of proteinuria. While overt proteinuria and podocyte effacement persist, 1D11 prevents total podocytes detachment, which might be a key event activating fibrogenic events in glomeruli. PMID- 27187582 TI - Neonatal Mortality of Planned Home Birth in the United States in Relation to Professional Certification of Birth Attendants. AB - INTRODUCTION: Over the last decade, planned home births in the United States (US) have increased, and have been associated with increased neonatal mortality and other morbidities. In a previous study we reported that neonatal mortality is increased in planned home births but we did not perform an analysis for the presence of professional certification status. PURPOSE: The objective of this study therefore was to undertake an analysis to determine whether the professional certification status of midwives or the home birth setting are more closely associated with the increased neonatal mortality of planned midwife attended home births in the United States. MATERIALS AND METHODS: This study is a secondary analysis of our prior study. The 2006-2009 period linked birth/infant deaths data set was analyzed to examine total neonatal deaths (deaths less than 28 days of life) in term singleton births (37+ weeks and newborn weight >= 2,500 grams) without documented congenital malformations by certification status of the midwife: certified nurse midwives (CNM), nurse midwives certified by the American Midwifery Certification Board, and "other" or uncertified midwives who are not certified by the American Midwifery Certification Board. RESULTS: Neonatal mortality rates in hospital births attended by certified midwives were significantly lower (3.2/10,000, RR 0.33 95% CI 0.21-0.53) than home births attended by certified midwives (NNM: 10.0/10,000; RR 1) and uncertified midwives (13.7/10,000; RR 1.41 [95% CI, 0.83-2.38]). The difference in neonatal mortality between certified and uncertified midwives at home births did not reach statistical levels (10.0/10,000 births versus 13.7/10,000 births p = 0.2). CONCLUSIONS: This study confirms that when compared to midwife-attended hospital births, neonatal mortality rates at home births are significantly increased. While NNM was increased in planned homebirths attended by uncertified midwives when compared to certified midwives, this difference was not statistically significant. Neonatal mortality rates at home births were not significantly different in relationship to professional certification status of the birth attendant, whether the delivery was by a certified or an uncertified birth attendant. PMID- 27187583 TI - Time order reversals and saccades. AB - Ballistic eye movements, or saccades, present a major challenge to the visual system. They generate a rapid blur of movement across the surface of the retinae that is rarely consciously seen, as awareness of input is suppressed around the time of a saccade. Saccades are also associated with a number of perceptual distortions. Here we are primarily interested in a saccade-induced illusory reversal of apparent temporal order. We examine the apparent order of transient targets presented around the time of saccades. In agreement with previous reports, we find evidence for an illusory reversal of apparent temporal order when the second of two targets is presented during a saccade - but this is only apparent for some observers. This contrasts with the apparent salience of targets presented during a saccade, which is suppressed for all observers. Our data suggest that separable processes might underlie saccadic suppressions of salience and saccade-induced reversals of apparent order. We suggest the latter arises when neural transients, normally used for timing judgments, are suppressed due to a saccade - but that this is an insufficient pre-condition. We therefore make the further suggestion, that the loss of a neural transient must be coupled with a specific inferential strategy, whereby some people assume that when they lack a clear impression of event timing, that event must have happened less recently than alternate events for which they have a clear impression of timing. PMID- 27187585 TI - Local effect of bisphenol A on the estradiol synthesis of ovarian granulosa cells from PCOS. AB - Close relationship between polycystic ovary syndrome (PCOS) and bisphenol A (BPA) has drawn much attention in recent years, while the underlying mechanisms are poorly understood. In our study, we aim to detect BPA concentration in the follicular fluid and investigate its effect on estradiol synthesis in human granulosa cells from PCOS and non-PCOS patients. Follicular fluid and granulosa cells were collected from women who underwent controlled ovarian stimulation for in vitro fertilization or intracytoplasmic sperm injection. BPA concentration in the follicular fluid from PCOS patients (440.50 +/- 63.70 pg/ml) was significantly higher than that from non-PCOS patients (338.00 +/- 57.88 pg/ml). Expression of aromatase and estradiol synthesis in cultured granulosa cells was examined after treatment with BPA from 0.01 to 1 MUM for 24 h. Expression of aromatase and estradiol synthesis was downregulated by BPA in a dose-dependent manner in PCOS, but no effect was observed in granulosa cells from non-PCOS patients. These findings provide evidence that increased BPA concentration in the follicular fluid of PCOS patients may play an important role in its pathogenesis by attenuating the expression of aromatase in granulosa cells. PMID- 27187584 TI - Individual differences in the shape of the nasal visual field. AB - Between-subject differences in the shape of the nasal visual field were assessed for 103 volunteers 21-85years of age and free of visual disorder. Perimetry was conducted with a stimulus for which contrast sensitivity is minimally affected by peripheral defocus and decreased retinal illumination. One eye each was tested for 103 volunteers free of eye disease in a multi-center prospective longitudinal study. A peripheral deviation index was computed as the difference in log contrast sensitivity at outer (25-29 degrees nasal) and inner (8 degrees from fixation) locations. Values for this index ranged from 0.01 (outer sensitivity slightly greater than inner sensitivity) to -0.7 log unit (outer sensitivity much lower than inner sensitivity). Mean sensitivity for the inner locations was independent of the deviation index (R2<1%), while mean sensitivity for the outer locations was not (R2=38%, p<0.0005). Age was only modestly related to the index, with a decline by 0.017 log unit per decade (R2=10%). Test-retest data for 21 volunteers who completed 7-10 visits yielded standard deviations for the index from 0.04 to 0.17 log unit, with a mean of 0.09 log unit. Between-subject differences in peripheral deviation persisted over two years of longitudinal testing. Peripheral deviation indices were correlated with indices for three other perimetric stimuli used in a subset of 24 volunteers (R2 from 20% to 49%). Between-subject variability in shape of the visual field raises concerns about current clinical visual field indices, and further studies are needed to develop improved indices. PMID- 27187586 TI - Asymmetric Roadmap to Diverse Polycyclic Benzopyrans via Phosphine-Catalyzed Enantioselective [4 + 2]-Annulation Reaction. AB - The catalytic addition of the amino acid derived bifunctional N acylaminophosphine to an alpha-substituted allene ester generated a zwitterionic dipole that engaged the vinylogous ester function of 3-cyano-chromones in a [4 + 2] annulation reaction to deliver tetrahydroxanthones embodying three consecutive chiral centers in high yields and with excellent enantioselectivities. The established asymmetric synthesis further paves the way to two different classes of complex, sp(3)-rich tetracyclic benzopyrans via efficient cascade reactions. PMID- 27187587 TI - Similarities between adult female crack cocaine users and adolescents in risky decision-making scenarios. AB - BACKGROUND: Although previous studies have shown that both adolescence and drug addiction can influence risk-taking and decision-making processes, the underlying mechanisms remain unclear. Specifically, there is a lack of evidence as to whether these conditions could affect deliberative and affective processes involved in risk taking, such as feedback learning and valuation of profits and risk. OBJECTIVES: The objectives were to compare the role of feedback and the use of information in risk-taking behavior between female crack cocaine users and adolescents. Additionally, we aimed to investigate whether sensation seeking, impulsivity, depressive and anxiety symptoms, executive functioning, and working memory performance could explain differences in risk-taking behavior. METHOD: This is a quasi-experimental study comparing 27 low-income adult female crack cocaine users (CU) to 18 female adolescents (AD) within two conditions (no feedback or delayed-feedback) of the Columbia Card Task (CCT). In order to investigate CCT reference values for adult females, we also included 20 female non-drug-users with regular education and income as a reference group (RG). RESULTS: A similar pattern of risk-taking behavior was found between CU and AD within the CCT no-feedback condition. When delayed feedback was provided, AD exhibited a similar pattern of risk-taking behavior in the no-feedback condition, while CU showed a reduction of risk-taking behavior. Both groups exhibited higher risk taking than the RG within the CCT no-feedback condition, but only the AD group showed higher risk-taking behavior within the CCT feedback condition. Depressive symptom severity and working memory deficits were associated with higher risk-taking behaviors in CU. Executive functioning deficits were associated with higher risk-taking behavior in AD. CONCLUSIONS: Adult female crack cocaine users and female adolescents took similar risks during risky decision-making scenarios where feedback about their own performance was absent. However, when participants were provided with such feedback, it modulated risk taking behaviors in crack cocaine users but not in adolescents. PMID- 27187588 TI - Metabolic impact of combined hormonal contraceptives containing estradiol. AB - INTRODUCTION: Is the replacement of ethinyl-estradiol (EE) with estradiol (E2) in combined hormonal contraceptives (CHCs) associated with fewer metabolic effects, leading to a further improvement on safety of hormonal contraceptives? AREAS COVERED: This is a narrative review paper including all available data on the metabolic impact of CHCs containing E2 published in English up to December 2015. Modification of a metabolic variable of interest during the first months of treatment was considered as an outcome. EXPERT OPINION: E2 was extensively used in oral contraceptives associated to nomegestrol acetate (NOMAc) in a monophasic 24 + 4 or its ester E2 valerate to dienogest (DNG) in a quadriphasic 26 + 2 regimen. The impact on the lipid metabolism and the hemostatic system of these preparations seems milder than that caused by EE-based ones, associated with no change of blood pressure. The impact on bone metabolism was instead similar to EE. Data available in the literature are mainly derived from studies having secondary minor metabolic outcomes as the primary end-point, and so currently not completely applicable on the real variables of interest (arterial or venous cardiovascular events, bone fractures). The preliminar parenteral use of E2 seems promising, both transdermal and vaginal, in particular after the introduction of a specific progestin with a high anti-ovulatory activity, like nestorone. PMID- 27187589 TI - Des-gamma-Carboxyprothrombin Plasma Level in Diagnosis of Hepatocellular Carcinoma in a Chinese Population Undergoing Surgery. AB - BACKGROUND The usefulness of Des-g-carboxyprothrombin (DCP) has been indicated in areas where hepatitis C virus is prevalent. DCP has yet to be used in China. The aim of this study was to evaluate the usefulness of DCP in Chinese patients with hepatocellular carcinoma (HCC) predominantly caused by hepatitis B. MATERIAL AND METHODS 329 subjects with HCC and 371 subjects without HCC that all underwent surgery were consecutively enrolled. Serum AFP and plasma DCP levels in all subjects and 153 healthy volunteers were measured and analyzed. RESULTS Of 329 subjects with HCC, 258 (78.4%) were HBsAg positive. The median level of plasma DCP was 853.72 mAU/mL in subjects with HCC, 26.43 mAU/mL in subjects without HCC, and 29.91 m AU/mL in healthy volunteers. A cut-off DCP value of 87 mAU/mL yielded the optimal sensitivity of 74.80% and a specificity of 83.33% for differentiating subjects with HCC from subjects without HCC. The combination of AFP of 21.33 ng/mL and DCP of 87 mAU/mL had a sensitivity of 82.60% for tumors no larger than 2 cm, as well as a sensitivity of 90% for tumors larger than 5 cm. CONCLUSIONS The combination of DCP and AFP yielded great improvement in sensitivity in differentiating subjects with HCC from subjects without HCC. These two markers may be incorporated in the protocol for surveillance and diagnosis of HCC in the high-risk Chinese population. PMID- 27187590 TI - Epicardial Adipose Tissue Is Associated with Plaque Burden and Composition and Provides Incremental Value for the Prediction of Cardiac Outcome. A Clinical Cardiac Computed Tomography Angiography Study. AB - OBJECTIVES: We sought to investigate the association of epicardial adipose tissue (eCAT) volume with plaque burden, circulating biomarkers and cardiac outcomes in patients with intermediate risk for coronary artery disease (CAD). METHODS AND RESULTS: 177 consecutive outpatients at intermediate risk for CAD and completed biomarker analysis including high-sensitive Troponin T (hs-TnT) and hs-CRP underwent 256-slice cardiac computed tomography angiography (CCTA) between June 2008 and October 2011. Patients with lumen narrowing >=50% exhibited significantly higher eCAT volume than patients without any CAD or lumen narrowing <50% (median (interquartile range, IQR): 108 (73-167) cm3 vs. 119 (82-196) cm3, p = 0.04). Multivariate regression analysis demonstrated an independent association eCAT volume with plaque burden by number of lesions (R2 = 0.22, rpartial = 0.29, p = 0.026) and CAD severity by lumen narrowing (R2 = 0.22, rpartial = 0.23, p = 0.038) after adjustment for age, diabetes mellitus, hyperlidipemia, body-mass index (BMI), hs-CRP and hs-TnT. Univariate Cox proportional hazards regression analysis identified a significant association for both increased eCAT volume and maximal lumen narrowing with all cardiac events. Multivariate Cox proportional hazards regression analysis revealed an independent association of increased eCAT volume with all cardiac events after adjustment for age, >3 risk factors, presence of CAD, hs-CRP and hs-TnT. CONCLUSION: Epicardial adipose tissue volume is independently associated with plaque burden and maximum luminal narrowing by CCTA and may serve as an independent predictor for cardiac outcomes in patients at intermediate risk for CAD. PMID- 27187591 TI - G-Protein/beta-Arrestin-Linked Fluctuating Network of G-Protein-Coupled Receptors for Predicting Drug Efficacy and Bias Using Short-Term Molecular Dynamics Simulation. AB - The efficacy and bias of signal transduction induced by a drug at a target protein are closely associated with the benefits and side effects of the drug. In particular, partial agonist activity and G-protein/beta-arrestin-biased agonist activity for the G-protein-coupled receptor (GPCR) family, the family with the most target proteins of launched drugs, are key issues in drug discovery. However, designing GPCR drugs with appropriate efficacy and bias is challenging because the dynamic mechanism of signal transduction induced by ligand-receptor interactions is complicated. Here, we identified the G-protein/beta-arrestin linked fluctuating network, which initiates large-scale conformational changes, using sub-microsecond molecular dynamics (MD) simulations of the beta2-adrenergic receptor (beta2AR) with a diverse collection of ligands and correlation analysis of their G protein/beta-arrestin efficacy. The G-protein-linked fluctuating network extends from the ligand-binding site to the G-protein-binding site through the connector region, and the beta-arrestin-linked fluctuating network consists of the NPxxY motif and adjacent regions. We confirmed that the averaged values of fluctuation in the fluctuating network detected are good quantitative indexes for explaining G protein/beta-arrestin efficacy. These results indicate that short-term MD simulation is a practical method to predict the efficacy and bias of any compound for GPCRs. PMID- 27187592 TI - Pycnosomes: Condensed Endosomal Structures Secreted by Dictyostelium Amoebae. AB - Dictyostelium discoideum has been used largely as a model organism to study the organization and function of the endocytic pathway. Here we describe dense structures present in D. discoideum endocytic compartments, which we named pycnosomes. Pycnosomes are constitutively secreted in the extracellular medium, from which they can be recovered by differential centrifugation. We identified the most abundant protein present in secreted pycnosomes, that we designated SctA. SctA defines a new family of proteins with four members in D. discoideum, and homologous proteins in other protists and eumetazoa. We developed a monoclonal antibody specific for SctA and used it to further characterize secreted and intracellular pycnosomes. Within cells, immunofluorescence as well as electron microscopy identified pycnosomes as SctA-enriched dense structures in the lumen of endocytic compartments. Pycnosomes are occasionally seen in continuity with intra-endosomal membranes, particularly in U18666A-treated cells where intraluminal budding is highly enhanced. While the exact nature, origin and cellular function of pycnosomes remain to be established, this study provides a first description of these structures as well as a characterization of reagents that can be used for further studies. PMID- 27187593 TI - Personal Protection of Permethrin-Treated Clothing against Aedes aegypti, the Vector of Dengue and Zika Virus, in the Laboratory. AB - BACKGROUND: The dengue and Zika viruses are primarily transmitted by Aedes aegypti mosquitoes, which are most active during day light hours and feed both in and outside of the household. Personal protection technologies such as insecticide-treated clothing could provide individual protection. Here we assessed the efficacy of permethrin-treated clothing on personal protection in the laboratory. METHODS: The effect of washing on treated clothing, skin coverage and protection against resistant and susceptible Ae. aegypti was assessed using modified WHO arm-in-cage assays. Coverage was further assessed using free-flight room tests to investigate the protective efficacy of unwashed factory-dipped permethrin-treated clothing. Clothing was worn as full coverage (long sleeves and trousers) and partial coverage (short sleeves and shorts). Residual permethrin on the skin and its effect on mosquitoes was measured using modified WHO cone assays and quantified using high-pressure liquid chromatography (HPLC) analysis. RESULTS: In the arm-in-cage assays, unwashed clothing reduced landing by 58.9% (95% CI 49.2-66.9) and biting by 28.5% (95% CI 22.5-34.0), but reduced to 18.5% (95% CI 14.7-22.3) and 11.1% (95% CI 8.5-13.8) respectively after 10 washes. Landing and biting for resistant and susceptible strains was not significantly different (p<0.05). In free-flight room tests, full coverage treated clothing reduced landing by 24.3% (95% CI 17.4-31.7) and biting by 91% (95% CI 82.2-95.9) with partial coverage reducing landing and biting by 26.4% (95% CI 20.3-31.2) and 49.3% (95% CI 42.1-59.1) respectively with coverage type having no significant difference on landing (p<0.05). Residual permethrin was present on the skin in low amounts (0.0041mg/cm2), but still produced a KD of >80% one hour after wearing treated clothing. CONCLUSION: Whilst partially covering the body with permethrin-treated clothing provided some protection against biting, wearing treated clothing with long sleeves and trousers provided the highest form of protection. Washing treated clothing dramatically reduced protection provided. Permethrin-treated clothing could provide protection to individuals from Ae. aegypti that show permethrin resistance. Additionally, it could continue to provide protection even after the clothing has been worn. Field trials are urgently needed to determine whether clothing can protect against dengue and Zika. PMID- 27187595 TI - High incidence of oral corticosteroids prescriptions in children with asthma in early childhood. AB - OBJECTIVE: Severe asthma exacerbations are often treated with short courses of oral corticosteroids (OCS). This study assessed the incidence of OCS being prescribed in asthmatic children of various age groups and calculated their chances of receiving subsequent OCS prescriptions. METHODS: Longitudinal Dutch community pharmacy data of 2272 children who were regular users of asthma medication was analyzed retrospectively. Incidence rates for first, second and third prescriptions of OCS were calculated, stratified by age and sex. Probabilities of receiving first, second or third OCS prescriptions were assessed with Kaplan-Meier analysis. RESULTS: Incidence rates for first OCS prescriptions were 4.5 for the 1(st) year of life per 100 person-years (100PY); 3.9 for the 2(nd); 4.6 for the 3(rd); 4.2 for the 4(th), and 4.7 for the 5(th) year of life per 100PY. This was relatively high compared to incidence rates for children between the ages of 6 and 11 (ranging between 2.2 per 100PY (age 9) and 3.7(age 11)). Incidence rates for second and third OCS prescriptions were very high: 78.2(95%CI: 45.0-123.7) and 241.2(95%CI: 81.2-583.4) per 100PY for infants, respectively. The chances of receiving a first OCS prescription was higher in males (P value < 0.01). CONCLUSIONS: In the Netherlands, the incidence of OCS being prescribed to children being treated with asthma medication in early childhood is relatively high for first OCS prescriptions and extremely high for second and third OCS prescriptions compared to other ages. Furthermore, there is a high probability of receiving a further OCS prescription shortly after an OCS prescription. PMID- 27187594 TI - The Commercial Antibodies Widely Used to Measure H3 K56 Acetylation Are Non Specific in Human and Drosophila Cells. AB - Much of our understanding of the function of histone post-translational modifications in metazoans is inferred from their genomic localization and / or extrapolated from yeast studies. For example, acetylation of histone H3 lysine 56 (H3 K56Ac) is assumed to be important for transcriptional regulation in metazoan cells based on its occurrence at promoters and its function in yeast. Here we directly assess the function of H3 K56Ac during chromatin disassembly from gene regulatory regions during transcriptional induction in human cells by using mutations that either mimic or prevent H3 K56Ac. Although there is rapid histone H3 disassembly during induction of some estrogen receptor responsive genes, depletion of the histone chaperone ASF1A/B, which is required for H3 K56 acetylation, has no effect on chromatin disassembly at these regions. During the course of this work, we found that all the commercially available antibodies to H3 K56Ac are non-specific in human cells and in Drosophila. We used H3-YFP fusions to show that the H3 K56Q mutation can promote chromatin disassembly from regulatory regions of some estrogen responsive genes in the context of transcriptional induction. However, neither the H3 K56R nor K56Q mutation significantly altered chromatin disassembly dynamics by FRAP analysis. These results indicate that unlike the situation in yeast, human cells do not use H3 K56Ac to promote chromatin disassembly from regulatory regions or from the genome in general. Furthermore, our work highlights the need for rigorous characterization of the specificity of antibodies to histone post-translational modifications in vivo. PMID- 27187596 TI - Fine-Scale Habitat Segregation between Two Ecologically Similar Top Predators. AB - Similar, coexisting species often segregate along the spatial ecological axis. Here, we examine if two top predators (jaguars and pumas) present different fine scale habitat use in areas of coexistence, and discuss if the observed pattern can be explained by the risk of interference competition between them. Interference competition theory predicts that pumas should avoid habitats or areas used by jaguars (the dominant species), and as a consequence should present more variability of niche parameters across study areas. We used non-invasive genetic sampling of faeces in 12 different areas and sensor satellite fine-scale habitat indices to answer these questions. Meta-analysis confirmed differences in fine-scale habitat use between jaguars and pumas. Furthermore, average marginality of the realized niches of pumas was more variable than those of jaguars, and tolerance (a measure of niche breadth) was on average 2.2 times higher in pumas than in jaguars, as expected under the interference competition risk hypothesis. The use of sensor satellite fine-scale habitat indices allowed the detection of subtle differences in the environmental characteristics of the habitats used by these two similar top predators, which, as a rule, until now were recorded using the same general habitat types. The detection of fine spatial segregation between these two top predators was scale-dependent. PMID- 27187597 TI - Improved motion-sensitized driven-equilibrium preparation for 3D turbo spin echo T1 weighted imaging after gadolinium administration for the detection of brain metastases on 3T MRI. AB - OBJECTIVE: To evaluate the clinical usefulness of an improved motion-sensitized driven-equilibrium (iMSDE) preparation for three-dimensional turbo spin echo (TSE) T1 weighted imaging after gadolinium administration in 3.0-T MRI for the detection of brain metastases compared with conventional gradient echo (C-GRE) T1 weighted imaging with gadolinium. METHODS: 40 patients with suspected brain metastases underwent MR studies, including two contrast-enhanced sequences, iMSDE TSE and C-GRE. Post-enhancement images of 14 patients with suspected metastatic brain lesions were retrospectively analyzed, and comparisons between iMSDE-TSE and C-GRE were made using the Wilcoxon signed-rank test. RESULTS: C-GRE detected 86 metastatic lesions, whereas iMSDE-TSE detected 97, including one false positive lesion on both sequences. 11 of 96 metastases were detected on iMSDE-TSE only. On C-GRE, 15 of 85 metastases were equivocal. There was a significant difference between C-GRE and iMSDE-TSE in terms of the number of detected lesions (p = 0.024). Notably, the interobserver agreement for diagnosing metastases and identifying non-metastases was nearly identical. Overall, iMSDE-TSE achieves higher detectability of metastatic brain lesions, especially equivocal lesions. CONCLUSION: Compared with C-GRE, iMSDE-TSE detected more brain metastases. This method is especially helpful in discerning equivocal metastases. ADVANCES IN KNOWLEDGE: Previous studies have offered limited clinically useful information because they have all been preliminary studies such as comparing the contrast-to noise ratio of each sequence without evaluating iMSDE-TSE. This study, however, is unique because we evaluate the clinical usefulness of iMSDE-TSE for the detection of brain metastases, and we compare these results to C-GRE. PMID- 27187598 TI - Evaluation of diffusivity in pituitary adenoma: 3D turbo field echo with diffusion-sensitized driven-equilibrium preparation. AB - OBJECTIVE: Diffusivity of pituitary adenoma has not been investigated fully. The purpose of this study was to evaluate the feasibility of turbo field echo with diffusion-sensitized driven-equilibrium (DSDE-TFE) preparation for pituitary adenoma in the sella turcica and unaffected anterior lobe of the pituitary gland. METHODS: This retrospective study included 23 adult patients with pituitary adenomas. Among them, 6 each were prolactin-producing adenomas and growth hormone producing adenomas (GH) and the remaining 11 were non-functioning adenomas (NON). The apparent diffusion coefficients (ADCs) were measured in the pituitary adenoma and in the unaffected pituitary gland using coronal reformatted plane. RESULTS: All pituitary adenomas were clearly visualized on DSDE-TFE and ADC maps without obvious geometrical distortion. There were no statistically significant differences in ADC of the all pituitary adenoma (1.50 +/- 0.61 * 10(-3) mm(2) s( 1)) and the unaffected anterior lobe of the pituitary gland (1.49 +/- 0.37 * 10( 3) mm(2) s(-1), p = 0.99). The ADC in prolactin-producing adenomas (2.04 +/- 0.76 * 10(-3) mm(2) s(-1)) was significantly higher than that in GH (1.26 +/- 0.47 * 10(-3) mm(2) s(-1); p < 0.05) and NON (1.33 +/- 0.42 * 10(-3) mm(2) s(-1); p = 0.04). There was no statistically significant difference between GH and NON (p = 0.97). The intraclass correlation coefficient for ADC was 0.985 in adenomas and 0.635 in unaffected glands. CONCLUSION: With its insensitivity to field inhomogeneity and high spatial resolution, DSDE-TFE proved a feasible method for evaluating the diffusivity in the pituitary gland and adenoma. ADVANCES IN KNOWLEDGE: DSDE-TFE could enable us to assess ADC of pituitary adenoma in the sella turcica with high resolution and few susceptibility artefacts. PMID- 27187599 TI - Arterial input functions in dynamic contrast-enhanced magnetic resonance imaging: which model performs best when assessing breast cancer response? AB - OBJECTIVE: To evaluate the performance of six models of population arterial input function (AIF) in the setting of primary breast cancer and neoadjuvant chemotherapy (NAC). The ability to fit patient dynamic contrast-enhanced MRI (DCE MRI) data, provide physiological plausible data and detect pathological response was assessed. METHODS: Quantitative DCE-MRI parameters were calculated for 27 patients at baseline and after 2 cycles of NAC for 6 AIFs. Pathological complete response detection was compared with change in these parameters from a reproduction cohort of 12 patients using the Bland-Altman approach and receiver operating characteristic analysis. RESULTS: There were fewer fit failures pre-NAC for all models, with the modified Fritz-Hansen having the fewest pre-NAC (3.6%) and post-NAC (18.8%), contrasting with the femoral artery AIF (19.4% and 43.3%, respectively). Median transfer constant values were greatest for the Weinmann function and also showed greatest reductions with treatment (-68%). Reproducibility (r) was the lowest for the Weinmann function (r = -49.7%), with other AIFs ranging from r = -27.8 to -39.2%. CONCLUSION: Using the best performing AIF is essential to maximize the utility of quantitative DCE-MRI parameters in predicting response to NAC treatment. Applying our criteria, the modified Fritz-Hansen and cosine bolus approximated Parker AIF models performed best. The Fritz-Hansen and biexponential approximated Parker AIFs performed less well, and the Weinmann and femoral artery AIFs are not recommended. ADVANCES IN KNOWLEDGE: We demonstrate that using the most appropriate AIF can aid successful prediction of response to NAC in breast cancer. PMID- 27187601 TI - Trauma whole-body MDCT: an assessment of image quality in conventional dual-phase and modified biphasic injection. AB - OBJECTIVE: To compare the image quality of conventional arterial and portal venous (PV) phase multidetector CT (MDCT) with two biphasic injection protocols in polytrauma patients. METHODS: 60 consecutive patients with polytrauma underwent body 256-slice MDCT with a conventional protocol or 1 of 2 single-pass biphasic protocols: Group A, arterial (30 s) and PV (60 s) phase acquisitions; Group B, "biphasic" contrast injection with a single acquisition at 60 s; and Group C, "modified biphasic" injection with a single acquisition at a 70-s delay. Images were analyzed for arterial, venous and parenchymal attenuation profiles with regions of interest in the major arteries, veins and solid abdominal organs. A 5-point scoring system was used to assess the image quality, with 5 representing excellent arterial, venous and parenchymal opacification and <3 representing non-diagnostic opacification. In addition, the effective dose (millisieverts) was compared between the groups. RESULTS: In 93% of patients, image quality was scored as good or excellent (>=4). All studies were of satisfactory diagnostic quality. Overall, venous and arterial attenuation profiles were comparable. Attenuation profiles in the solid abdominal viscera were significantly higher (p < 0.01) using both biphasic protocols than with arterial or PV phase of conventional protocols. Effective doses were higher in Group A. CONCLUSION: Comparable image quality can be achieved using a biphasic i.v. contrast injection protocol with single MDCT acquisition with less radiation and reduction in acquisition time. ADVANCES IN KNOWLEDGE: For these particular biphasic injection protocols, we have shown that image quality is comparable with a conventional protocol. This has been achieved by comparing enhanced densities of specific structures, as well as gestalt scoring by assessors, on a 256-slice MDCT. PMID- 27187603 TI - Interview with Thomas Lundback, PhD. PMID- 27187600 TI - Is the false-positive rate in mammography in North America too high? AB - The practice of investigating pathological abnormalities in the breasts of females who are asymptomatic is primarily employed using X-ray mammography. The importance of breast screening is reflected in the mortality-based benefits observed among females who are found to possess invasive breast carcinoma prior to the manifestation of clinical symptoms. It is estimated that population-based screening constitutes a 17% reduction in the breast cancer mortality rate among females affected by invasive breast carcinoma. In spite of the significant utility that screening confers in those affected by invasive cancer, limitations associated with screening manifest as potential harms affecting individuals who are free of invasive disease. Disease-free and benign tumour-bearing individuals who are subjected to diagnostic work-up following a screening examination constitute a population of cases referred to as false positives (FPs). This article discusses factors contributing to the FP rate in mammography and extends the discussion to an assessment of the consequences associated with FP reporting. We conclude that the mammography FP rate in North America is in excess based upon the observation of overtreatment of in situ lesions and the disproportionate distribution of detriment and benefit among the population of individuals recalled for diagnostic work-up subsequent to screening. To address the excessive incidence of FPs in mammography, we investigate solutions that may be employed to remediate the current status of the FP rate. Subsequently, it can be suggested that improvements in the breast-screening protocol, medical litigation risk, image interpretation software and the implementation of image acquisition modalities that overcome superimposition effects are promising solutions. PMID- 27187605 TI - Transcriptional Characterization of Compounds: Lessons Learned from the Public LINCS Data. AB - The NIH-funded LINCS program has been initiated to generate a library of integrated, network-based, cellular signatures (LINCS). A novel high-throughput gene-expression profiling assay known as L1000 was the main technology used to generate more than a million transcriptional profiles. The profiles are based on the treatment of 14 cell lines with one of many perturbation agents of interest at a single concentration for 6 and 24 hours duration. In this study, we focus on the chemical compound treatments within the LINCS data set. The experimental variables available include number of replicates, cell lines, and time points. Our study reveals that compound characterization based on three cell lines at two time points results in more genes being affected than six cell lines at a single time point. Based on the available LINCS data, we conclude that the most optimal experimental design to characterize a large set of compounds is to test them in duplicate in three different cell lines. Our conclusions are constrained by the fact that the compounds were profiled at a single, relative high concentration, and the longer time point is likely to result in phenotypic rather than mechanistic effects being recorded. PMID- 27187604 TI - Development and Implementation of a High-Throughput High-Content Screening Assay to Identify Inhibitors of Androgen Receptor Nuclear Localization in Castration Resistant Prostate Cancer Cells. AB - Patients with castration-resistant prostate cancer (CRPC) can be treated with abiraterone, a potent inhibitor of androgen synthesis, or enzalutamide, a second generation androgen receptor (AR) antagonist, both targeting AR signaling. However, most patients relapse after several months of therapy and a majority of patients with relapsed CRPC tumors express the AR target gene prostate-specific antigen (PSA), suggesting that AR signaling is reactivated and can be targeted again to inhibit the relapsed tumors. Novel small molecules capable of inhibiting AR function may lead to urgently needed therapies for patients resistant to abiraterone, enzalutamide, and/or other previously approved antiandrogen therapies. Here, we describe a high-throughput high-content screening (HCS) campaign to identify small-molecule inhibitors of AR nuclear localization in the C4-2 CRPC cell line stably transfected with GFP-AR-GFP (2GFP-AR). The implementation of this HCS assay to screen a National Institutes of Health library of 219,055 compounds led to the discovery of 3 small molecules capable of inhibiting AR nuclear localization and function in C4-2 cells, demonstrating the feasibility of using this cell-based phenotypic assay to identify small molecules targeting the subcellular localization of AR. Furthermore, the three hit compounds provide opportunities to develop novel AR drugs with potential for therapeutic intervention in CRPC patients who have relapsed after treatment with antiandrogens, such as abiraterone and/or enzalutamide. PMID- 27187606 TI - Pinpointing the peripheral bias in neural scene-processing networks during natural viewing. AB - Peripherally presented stimuli evoke stronger activity in scene-processing regions than foveally presented stimuli, suggesting that scene understanding is driven largely by peripheral information. We used functional MRI to investigate whether functional connectivity evoked during natural perception of audiovisual movies reflects this peripheral bias. For each scene-sensitive region--the parahippocampal place area (PPA), retrosplenial cortex, and occipital place area- we computed two measures: the extent to which its activity could be predicted by V1 activity (connectivity strength) and the eccentricities within V1 to which it was most closely related (connectivity profile). Scene regions were most related to peripheral voxels in V1, but the detailed nature of this connectivity varied within and between these regions. The retrosplenial cortex showed the most consistent peripheral bias but was less predictable from V1 activity, while the occipital place area was related to a wider range of eccentricities and was strongly coupled to V1. We divided the PPA along its posterior-anterior axis into retinotopic maps PHC1, PHC2, and anterior PPA, and found that a peripheral bias was detectable throughout all subregions, though the anterior PPA showed a less consistent relationship to eccentricity and a substantially weaker overall relationship to V1. We also observed an opposite foveal bias in object-perception regions including the lateral occipital complex and fusiform face area. These results show a fine-scale relationship between eccentricity biases and functional correlation during natural perception, giving new insight into the structure of the scene-perception network. PMID- 27187607 TI - Quantitative determination of saroglitazar, a predominantly PPAR alpha agonist, in human plasma by a LC-MS/MS method utilizing electrospray ionization in a positive mode. AB - A sensitive LC-MS/MS method was developed and validated for quantitation of saroglitazar using turboion spray interface with positive ion mode. A liquid liquid extraction, with a mixture of dichloromethane and diethyl ether, was employed for the extraction of saroglitazar and glimepiride (IS) from human plasma. The chromatographic separation was achieved using an ACE-5, C18 (4.6 * 100 mm) column with a gradient mobile phase comprising acetonitrile and ammonium acetate buffer with trifluoracetic acid in purified water. Both analytes were separated within 10 min with retention times of 4.52 and 2.57 min for saroglitazar and IS, respectively. Saroglitazar quantitation was achieved by the summation of two MRM transition pairs (m/z 440.2 to m/z 366.0 and m/z 440.2 to m/z 183.1), while that of IS was achieved using transition pair m/z 491.3 to m/z 352.0. The calibration standards of saroglitazar showed linearity from 0.2 to 500 ng/mL, with a lower limit of quantitation of 0.2 ng/mL. The biases for inter- and intra-batch assays were -7.51-1.15% and -11.21 to -3.25%, respectively, while the corresponding precisions were 5.04-8.06% and 1.53-7.68%, respectively. The developed method was used to monitor the plasma concentrations of saroglitazar in clinical samples. PMID- 27187608 TI - Health 2000 score - development and validation of a novel cardiovascular risk score. AB - BACKGROUND: Previous risk scores for predicting myocardial infarctions and strokes have mainly been based on conventional risk factors. We aimed to develop a novel improved risk score that would incorporate other widely available clinical variables for predicting the broadest range of endpoints, including revascularizations. METHODS: A nationwide sample of 5843 Finns underwent a clinical examination in 2000-2001. The participants were followed for a median of 11.2 years for incident cardiovascular events. Model discrimination and calibration were assessed and internal validation was performed. RESULTS: Sex, age, systolic blood pressure, total cholesterol, HDL cholesterol, smoking status, parental death from cardiovascular disease, left ventricular hypertrophy, hemoglobin A1c, and educational level remained significant predictors of cardiovascular events (p <= 0.005 for all). The share of participants with >=10% estimated cardiovascular risk was 28.9%, 18.5%, 36.9% and 23.8% with the Health 2000, Finrisk, Framingham and Reynolds risk scores. The Health 2000 score (c statistic: 0.850) showed superior discrimination to the Framingham (c-statistic improvement: 0.021) and Reynolds (c-statistic improvement: 0.007) scores (p < 0.001 for both comparisons). Model including left ventricular hypertrophy, hemoglobin A1c, and educational level improved the model prediction (c-statistic improvement: 0.006, p = 0.003). CONCLUSIONS: The Health 2000score improves cardiovascular risk prediction in the current study population. KEY MESSAGES Previous risk scores for predicting myocardial infarctions and strokes have mainly been based on conventional risk factors. We aimed to develop a novel improved risk score that would incorporate other widely available clinical variables (including left ventricular hypertrophy, hemoglobin A1c, and education level) for predicting the broadest range of endpoints, including revascularizations. The Health 2000 score improved cardiovascular risk prediction in the current study population compared with traditional cardiovascular risk prediction scores. PMID- 27187609 TI - Toward the Validation of Maternal Embryonic Leucine Zipper Kinase: Discovery, Optimization of Highly Potent and Selective Inhibitors, and Preliminary Biology Insight. AB - MELK kinase has been implicated in playing an important role in tumorigenesis. Our previous studies suggested that MELK is involved in the regulation of cell cycle and its genetic depletion leads to growth inhibition in a subset of high MELK-expressing basal-like breast cancer cell lines. Herein we describe the discovery and optimization of novel MELK inhibitors 8a and 8b that recapitulate the cellular effects observed by short hairpin ribonucleic acid (shRNA)-mediated MELK knockdown in cellular models. We also discovered a novel fluorine-induced hydrophobic collapse that locked the ligand in its bioactive conformation and led to a 20-fold gain in potency. These novel pharmacological inhibitors achieved high exposure in vivo and were well tolerated, which may allow further in vivo evaluation. PMID- 27187610 TI - The use of whole exome sequencing for the diagnosis of autosomal recessive malignant infantile osteopetrosis. AB - Autosomal recessive malignant infantile osteopetrosis is a congenital disease characterized by pathologically increased bone density. Recently, the use of whole exome sequencing has been utilized as a clinical diagnostic tool in a number of Mendelian disorders. In this study, whole exome sequencing (WES) was successfully used in six patients with malignant infantile osteopetrosis (MIOP) and identified mutations in four MIOP-related genes (CLCN7, TCIRG1, SNX10, and TNFRSF11A). We report these patients, describe the mutations and review the current literature. PMID- 27187612 TI - Protein Nanocontainers from Nonviral Origin: Testing the Mechanics of Artificial and Natural Protein Cages by AFM. AB - Self-assembling protein nanocontainers are promising candidates for an increasingly wide scope of purposes. Their applications range from drug delivery vehicles and imaging agents to nanocompartments for controlled enzymatic activity. In order to exploit their full potential in these different fields, characterization of their properties is vital. For example, their mechanical properties give insight into the stability of a particle as a function of their internal content. The mechanics can be probed by atomic force microscopy nanoindentation, and while this single particle method is increasingly used to probe material properties of viral nanocages, it has hardly been used to characterize nonviral nanocages. Here we report nanoindentation studies on two types of nonviral nanocontainers: (i) lumazine synthase from Aquifex aeolicus (AaLS), which naturally self-assembles into icosahedral cages, and (ii) the artificial protein cage O3-33 originating from a computational design approach. In addition, we tested particles that had been engineered toward improved cargo loading capacity and compared these nanocages in empty and loaded states. We found that the thermostable AaLS cages are stiffer and resist higher forces before breaking than the O3-33 particles, but that mutations affecting the size of AaLS particles have a dramatic effect on their structural stability. Furthermore, we show that cargo packaging can occur while maintaining the cage's mechanical properties. PMID- 27187611 TI - Molecular Characterization of Three Canine Models of Human Rare Bone Diseases: Caffey, van den Ende-Gupta, and Raine Syndromes. AB - One to two percent of all children are born with a developmental disorder requiring pediatric hospital admissions. For many such syndromes, the molecular pathogenesis remains poorly characterized. Parallel developmental disorders in other species could provide complementary models for human rare diseases by uncovering new candidate genes, improving the understanding of the molecular mechanisms and opening possibilities for therapeutic trials. We performed various experiments, e.g. combined genome-wide association and next generation sequencing, to investigate the clinico-pathological features and genetic causes of three developmental syndromes in dogs, including craniomandibular osteopathy (CMO), a previously undescribed skeletal syndrome, and dental hypomineralization, for which we identified pathogenic variants in the canine SLC37A2 (truncating splicing enhancer variant), SCARF2 (truncating 2-bp deletion) and FAM20C (missense variant) genes, respectively. CMO is a clinical equivalent to an infantile cortical hyperostosis (Caffey disease), for which SLC37A2 is a new candidate gene. SLC37A2 is a poorly characterized member of a glucose-phosphate transporter family without previous disease associations. It is expressed in many tissues, including cells of the macrophage lineage, e.g. osteoclasts, and suggests a disease mechanism, in which an impaired glucose homeostasis in osteoclasts compromises their function in the developing bone, leading to hyperostosis. Mutations in SCARF2 and FAM20C have been associated with the human van den Ende-Gupta and Raine syndromes that include numerous features similar to the affected dogs. Given the growing interest in the molecular characterization and treatment of human rare diseases, our study presents three novel physiologically relevant models for further research and therapy approaches, while providing the molecular identity for the canine conditions. PMID- 27187614 TI - Vaccination against hepatitis A and B in patients with chronic liver disease and type 2 diabetes: has anything changed? AB - BACKGROUND & AIMS: Given the severity of acute hepatitis in patients with chronic liver diseases (CLD) and patients with type 2 diabetes (DM), most of these patients are recommended to be vaccinated. The aim is to assess the recent changes in HAV and HBV vaccination rates in patients with CLD and DM in the U.S. using the most recent population data. METHODS: We used the National Health and Nutrition Examination Surveys (NHANES) cycles 2009-2012 and 2013-2014, and compared those to previous cycles (1999-2004 and 2005-2008). RESULTS: In general U.S. population, the rates of quality measure (QM, serologic immunity or history of vaccination) for HBV increased from 31.9% in 1999-2004 to 49.5% in 2013-2014 (P < 0.0001), synchronously with an increase in self-reported HBV vaccination: from 24.4% to 41.3% (P < 0.0001). A similar increase was noted for HAV: 12.0% in 1999-2004 to 33.4% in 2013-2014 in vaccination, 44.0% to 52.4% in HAV QM (all P < 0.0001). Greater recent increases in HBV QM were noted in non-HBV CLD patients: 34.7% to 56.8% in HBV QM and 22.7% to 51.1% in HBV vaccination (all P < 0.0001), while the changes in patients with diabetes were similar to those in general U.S. population despite the recent CDC recommendation (for the age 19-59): 31.0% to 45.1% (P = 0.007) in HBV QM, and 22.3% to 39.0% (P = 0.0004) in HBV vaccination. CONCLUSIONS: Despite recommendations, HAV and HBV vaccination rates in patients with CLD and DM remain relatively low. Better vaccination strategies for these high risk patients should be undertaken. PMID- 27187613 TI - Viruses are a dominant driver of protein adaptation in mammals. AB - Viruses interact with hundreds to thousands of proteins in mammals, yet adaptation against viruses has only been studied in a few proteins specialized in antiviral defense. Whether adaptation to viruses typically involves only specialized antiviral proteins or affects a broad array of virus-interacting proteins is unknown. Here, we analyze adaptation in ~1300 virus-interacting proteins manually curated from a set of 9900 proteins conserved in all sequenced mammalian genomes. We show that viruses (i) use the more evolutionarily constrained proteins within the cellular functions they interact with and that (ii) despite this high constraint, virus-interacting proteins account for a high proportion of all protein adaptation in humans and other mammals. Adaptation is elevated in virus-interacting proteins across all functional categories, including both immune and non-immune functions. We conservatively estimate that viruses have driven close to 30% of all adaptive amino acid changes in the part of the human proteome conserved within mammals. Our results suggest that viruses are one of the most dominant drivers of evolutionary change across mammalian and human proteomes. PMID- 27187616 TI - A Source Area Approach Demonstrates Moderate Predictive Ability but Pronounced Variability of Invasive Species Traits. AB - The search for traits that make alien species invasive has mostly concentrated on comparing successful invaders and different comparison groups with respect to average trait values. By contrast, little attention has been paid to trait variability among invaders. Here, we combine an analysis of trait differences between invasive and non-invasive species with a comparison of multidimensional trait variability within these two species groups. We collected data on biological and distributional traits for 1402 species of the native, non-woody vascular plant flora of Austria. We then compared the subsets of species recorded and not recorded as invasive aliens anywhere in the world, respectively, first, with respect to the sampled traits using univariate and multiple regression models; and, second, with respect to their multidimensional trait diversity by calculating functional richness and dispersion metrics. Attributes related to competitiveness (strategy type, nitrogen indicator value), habitat use (agricultural and ruderal habitats, occurrence under the montane belt), and propagule pressure (frequency) were most closely associated with invasiveness. However, even the best multiple model, including interactions, only explained a moderate fraction of the differences in invasive success. In addition, multidimensional variability in trait space was even larger among invasive than among non-invasive species. This pronounced variability suggests that invasive success has a considerable idiosyncratic component and is probably highly context specific. We conclude that basing risk assessment protocols on species trait profiles will probably face hardly reducible uncertainties. PMID- 27187617 TI - Posterior Cervical Foraminotomy: Indications, Technique, and Outcomes. AB - Cervical radiculopathy presents with upper extremity pain, decreased sensation, and decreased strength caused by irritation of specific nerve root(s). After failure of conservative management, surgical options include anterior cervical decompression and fusion, disk arthroplasty, and posterior cervical foraminotomy. In this review, we discuss indications, techniques, and outcomes of posterior cervical laminoforaminotomy. PMID- 27187615 TI - ERK5 signalling rescues intestinal epithelial turnover and tumour cell proliferation upon ERK1/2 abrogation. AB - The ERK1/2 MAPK signalling module integrates extracellular cues that induce proliferation and differentiation of epithelial lineages, and is an established oncogenic driver, particularly in the intestine. However, the interrelation of the ERK1/2 module relative to other signalling pathways in intestinal epithelial cells and colorectal cancer (CRC) is unclear. Here we show that loss of Erk1/2 in intestinal epithelial cells results in defects in nutrient absorption, epithelial cell migration and secretory cell differentiation. However, intestinal epithelial cell proliferation is not impeded, implying compensatory mechanisms. Genetic deletion of Erk1/2 or pharmacological targeting of MEK1/2 results in supraphysiological activity of the ERK5 pathway. Furthermore, targeting both pathways causes a more effective suppression of cell proliferation in murine intestinal organoids and human CRC lines. These results suggest that ERK5 provides a common bypass route in intestinal epithelial cells, which rescues cell proliferation upon abrogation of ERK1/2 signalling, with therapeutic implications in CRC. PMID- 27187618 TI - Performing an Anterior Cervical Discectomy and Fusion. AB - An anterior cervical discectomy and fusion is one of the most common procedures performed in spine surgery. It allows for a direct decompression of the spinal cord and the neural foramen. When performed properly, the results of this procedure are some of the best in spine surgery. PMID- 27187619 TI - A peptide with a cysteine terminus: probe for label-free fluorescent detection of thrombin activity. AB - Thrombin has been implicated in atherosclerotic disease development. However, thrombin activity detection is currently limited because of the lack of convenient fluorescent probes. We developed a label-free fluorescent method to assay thrombin activity on the basis of a designed peptide probe with a thrombin cleavable peptide sequence and a cysteine terminus. The peptide probe can be conjugated to DNA-templated silver nanoclusters (DNA-AgNCs) through Ag-S bonding; as a result, the fluorescence of DNA-AgNCs was enhanced. As the DNA-AgNCs-peptide conjugate was adsorbed to graphene oxide (GO), the enhanced fluorescence of DNA AgNCs was quenched. Once the peptide probe was cleaved by thrombin, the resulting release of the DNA-AgNCs from the surface of GO restored the enhanced fluorescence. Thrombin can be determined with a linear range of 0.0-50.0 nM with a detection limit of 1 nM. The thrombin-sensitive probe with a cysteine terminus may be developed into probes to detect other proteases. PMID- 27187620 TI - Rasch analysis of the Norwegian version of the Arthritis Self-Efficacy Scale (ASES). AB - OBJECTIVES: To apply the Rasch model to the Norwegian version of the Arthritis Self-Efficacy Scale (ASES). METHOD: The ASES was included in a self-administered questionnaire sent to 224 patients attending one of three rehabilitation centres for rheumatic diseases in Norway in 2009. The fit of the ASES to the Rasch model was assessed together with hypothesized associations with the Modified Health Assessment Questionnaire (MHAQ), the 36-item Short Form Health Survey (SF-36), the numerical rating scale (NRS) for pain, and NRS fatigue. RESULTS: A total of 145 (64.7%) patients responded to the questionnaire. The two scales of other symptoms and pain showed good fit to the Rasch model with no evidence for differential item functioning (DIF) according to eight sociodemographic and disease-related variables. The Person Separation Index (PSI), which is equivalent to Cronbach's alpha, ranged from 0.74 to 0.78. Correlations with scores for other instruments were as hypothesized: ASES pain had the highest correlations with SF 36 pain and NRS pain and ASES other symptoms had the highest correlations with other aspects of the SF-36 and NRS fatigue. CONCLUSIONS: The ASES had good fit to the Rasch model and correlations with other instrument scores that followed hypotheses, lending further support to the application of the instrument in patients with rheumatic diseases. PMID- 27187621 TI - Both Complexity and Location of DNA Damage Contribute to Cellular Senescence Induced by Ionizing Radiation. AB - Persistent DNA damage is considered as a main cause of cellular senescence induced by ionizing radiation. However, the molecular bases of the DNA damage and their contribution to cellular senescence are not completely clear. In this study, we found that both heavy ions and X-rays induced senescence in human uveal melanoma 92-1 cells. By measuring senescence associated-beta-galactosidase and cell proliferation, we identified that heavy ions were more effective at inducing senescence than X-rays. We observed less efficient repair when DNA damage was induced by heavy ions compared with X-rays and most of the irreparable damage was complex of single strand breaks and double strand breaks, while DNA damage induced by X-rays was mostly repaired in 24 hours and the remained damage was preferentially associated with telomeric DNA. Our results suggest that DNA damage induced by heavy ion is often complex and difficult to repair, thus presents as persistent DNA damage and pushes the cell into senescence. In contrast, persistent DNA damage induced by X-rays is preferentially associated with telomeric DNA and the telomere-favored persistent DNA damage contributes to X rays induced cellular senescence. These findings provide new insight into the understanding of high relative biological effectiveness of heavy ions relevant to cancer therapy and space radiation research. PMID- 27187622 TI - Integrating mutation variant allele frequency into clinical practice in myeloid malignancies. AB - Hematologic myeloid neoplasms represent a heterogeneous group of disorders with defined clinical and pathologic characteristics. However, intensive investigation into the genetic abnormalities of these diseases has not only significantly advanced our understanding, but also revolutionized our diagnostic and prognostic capabilities. Moreover, more recent discovery on the impact of clonal burden has highlighted the critical and dynamic role of clonal evolution over time, which is integrally linked to a patient's clinical trajectory. This review will highlight the evidence supporting the incorporation of allelic burden of somatic mutations into clinical practice for the diagnosis and prognosis of myeloid neoplasms. PMID- 27187624 TI - Primary immunodeficiency and recalcitrant chronic sinusitis: a systematic review. AB - BACKGROUND: A subset of patients with chronic rhinosinusitis (CRS) has disease refractory to standard therapies. Primary immunodeficiency should be considered in this group. Past literature has demonstrated an association between immunodeficiency and chronic sinusitis. METHODS: A systematic literature search was performed using OVID, MEDLINE, EMBASE, and Cochrane databases to identify English language papers containing original human data on subjects with primary immunodeficiency and chronic sinusitis. A total of 39 studies met inclusion criteria. Data was collected pertaining to immune dysfunction in patients with chronic sinusitis, the clinical workup for these patients, and the effectiveness of medical and surgical treatments. The studies were assessed to determine their level of evidence. RESULTS: The majority of studies were supported by Level 4 evidence. Up to 50% of patients with recalcitrant CRS were found to have immune dysfunction. The most frequent primary immunodeficiencies studied were common variable immunodeficiency (CVID) and X-linked agammaglobulinemia (XLA). Common collected data included measurement of serum immunoglobulins and functional antibody responses. Treatments reviewed include immunoglobulin replacement, long term antibiotics and endoscopic sinus surgery. CONCLUSION: Patients with recalcitrant CRS should be evaluated for primary immunodeficiency. This should include as assessment of quantitative serum immunoglobulin levels as well as functional antibody responses. Medical therapy, particularly immunoglobulin replacement therapy, appears to be most effective when administered at high doses early in the disease course. The addition of surgery is less clearly supported, but may also provide benefit if performed early. PMID- 27187623 TI - Tickling the retina: integration of subthreshold electrical pulses can activate retinal neurons. AB - OBJECTIVE: The field of retinal prosthetics has made major progress over the last decade, restoring visual percepts to people suffering from retinitis pigmentosa. The stimulation pulses used by present implants are suprathreshold, meaning individual pulses are designed to activate the retina. In this paper we explore subthreshold pulse sequences as an alternate stimulation paradigm. Subthreshold pulses have the potential to address important open problems such as fading of visual percepts when patients are stimulated at moderate pulse repetition rates and the difficulty in preferentially stimulating different retinal pathways. APPROACH: As a first step in addressing these issues we used Gaussian white noise electrical stimulation combined with spike-triggered averaging to interrogate whether a subthreshold sequence of pulses can be used to activate the mouse retina. MAIN RESULTS: We demonstrate that the retinal network can integrate multiple subthreshold electrical stimuli under an experimental paradigm immediately relevant to retinal prostheses. Furthermore, these characteristic stimulus sequences varied in their shape and integration window length across the population of retinal ganglion cells. SIGNIFICANCE: Because the subthreshold sequences activate the retina at stimulation rates that would typically induce strong fading (25 Hz), such retinal 'tickling' has the potential to minimize the fading problem. Furthermore, the diversity found across the cell population in characteristic pulse sequences suggests that these sequences could be used to selectively address the different retinal pathways (e.g. ON versus OFF). Both of these outcomes may significantly improve visual perception in retinal implant patients. PMID- 27187625 TI - Trifluoromethylallylation of Heterocyclic C-H Bonds with Allylic Carbonates under Rhodium Catalysis. AB - The rhodium(III)-catalyzed gamma-trifluoromethylallylation of various heterocyclic C-H bonds with CF3-substituted allylic carbonates is described. These reactions provide direct access to linear CF3-containing allyl frameworks with complete trans-selectivity via C-H bond activation followed by a formal SN type reaction pathway. PMID- 27187626 TI - Bowel Preparation in Awake Craniotomy: An Overlooked Entity. PMID- 27187628 TI - Cognitive Functioning After Surgery in Middle-aged and Elderly Danish Twins. PMID- 27187627 TI - Evaluation of the Effect of Aneurysmal Clipping on Electrocardiography and Echocardiographic Changes in Patients With Subarachnoid Hemorrhage: A Prospective Observational Study. AB - BACKGROUND: Electrocardiographic (ECG) and echocardiographic changes that are subsequent to aneurysmal subarachnoid hemorrhage (a-SAH) are commonly observed with a prevalence varying from 27% to 100% and 13% to 18%, respectively. There are sparse data in the literature about the pattern of ECG and echocardiographic changes in patients with SAH after clipping of the aneurysm. Hence, we observed the effect of aneurysmal clipping on ECG and echocardiographic changes during the first week after surgery, and the impact of these changes on outcome at the end of 1 year. MATERIALS AND METHODS: This prospective, observational study was conducted in 100 consecutive patients with a-SAH undergoing clipping of ruptured aneurysm. ECG and echocardiographic changes were recorded preoperatively and every day after surgery until 7 days. Outcome was evaluated using the Glasgow outcome scale at the end of 1 year. RESULTS: Of 100 patients, 75 had ECG changes and 17 had echocardiographic changes preoperatively. The ECG changes observed were QTc prolongation, conduction defects, ST-wave and T-wave abnormalities, tachyarrhythmias, and bradyarrhythmias. The echocardiography changes included global hypokinesia and regional wall motion abnormalities. Both echocardiographic and ECG changes showed significant recovery on the first postoperative day. Patients presenting with both echocardiographic and ECG changes were found to require higher ionotropic support to maintain the desired blood pressure, and were associated with poor outcome (Glasgow outcome scale, 1 to 2) at 1 year after surgery. There was no association of ECG and echocardiographic changes with mortality (both in-hospital or at 1 year). CONCLUSIONS: The ECG changes, such as QTc prolongation, bradycardia, conduction abnormality, and echocardiographic changes, recover on postoperative day-1, in most of the cases after clipping. Patients with combined ECG and echocardiographic changes tend to have poor neurological outcome at the end of 1 year. PMID- 27187630 TI - Lead Relative Bioavailability in Lip Products and Their Potential Health Risk to Women. AB - Recent studies have investigated lead (Pb) concentrations in lip products but little is known about its oral bioavailability. In this study, 75 lipsticks and 18 lip glosses were assessed for Pb concentration, while 15 samples were assessed for Pb relative bioavailability (RBA, relative to Pb acetate absorption) using a mouse femur assay. Lead concentrations were 0.2-10 185 mg kg(-1), with 21 samples exceeding the Chinese limit of 40 mg kg(-1). Samples with orange and pink colors and/or low cost contained higher Pb concentrations. For samples with Pb > 7500 mg kg(-1), Pb was present due to the addition of lead chromate (PbCrO4) as a colorant, which was confirmed by X-ray absorption near-edge structure analysis. Lead-RBA in 15 samples (87-10 185 mg kg(-1)) ranged from 23% to 95%, being significantly higher in moderate Pb (56-95%; 87-300 mg kg(-1)) than high Pb samples (23-48%; >300 mg kg(-1)). The calculation of Pb intake based on Pb-RBA showed that lip product ingestion contributed 5.4-68% of the aggregate Pb exposure for women depending on Pb concentration. The high Pb concentration in some lip products together with their moderate Pb-RBA suggests that lip product ingestion is a potential health concern to women. PMID- 27187631 TI - Etiology of bone and joint infections: a case series of 363 consecutive patients from an orthopaedic infection unit. AB - BACKGROUND: Bone and joint infections remain a clinical challenge with potentially serious consequences. Nevertheless there is a lack of studies with strict criteria for diagnosis and etiology. The primary aim of this study was to determine the causative agents in orthopaedic infections using strict diagnostic criteria for infection and etiology. The secondary aim was to assess the timing of post-operative infections in relation to pathogens and to compare causative bacteria in different parts of the body. METHODS: A retrospective registry study of 363 consecutive cases of bone and joint infections was performed. Microbiological data on sampling and culture results were registered. RESULTS: Staphylococcus aureus dominated in both operated (45%) and non-operated (44%) patients, followed in frequency by coagulase-negative staphylococci (CoNS) in operated patients (11%) and beta-haemolytic streptococci in non-operated patients (16%) (p < 0.001). There were no polymicrobial infections in non-surgical cases (p < 0.001). For operated patients, Gram-negative bacilli were observed in 6%, almost exclusively isolated from the lower extremity. Propionibacterium spp. was the most common finding after spinal surgery. In 90/363 (25%), the agent responsible for the infection could not be defined according to the strict criteria used. CONCLUSION: S. aureus dominated as etiological agent in all bone and joint infections, including operated patient given peri-operative prophylaxis. Improved timing of antibiotic prophylaxis seen after the introduction of the Swedish national project PRISS may have changed this. The number of infections with uncertain etiology was high, stressing the importance of more studies on diagnostics, as well as strict diagnostic algorithms. PMID- 27187633 TI - Aun (n = 1,11) Clusters Interacting With Lone-Pair Ligands. AB - We analyze the pattern of binding energies (BEs) of small Aun clusters (n = 1-7, 11) with lone-pair ligands (L = H2O, SH2, NH3, PH3, PF3, PCl3, and PMe3) employing the density functional theory. We use PBE0 functional with the dispersion correction and scalar relativistic effective core potential. This approach provides correct BEs when compared with benchmark CCSD(T) calculations for Au-L and Au2-L complexes. The pattern of BEs of Aun-L complexes is irregular with BE for Au3 ~ Au4 > Au2 > Au7 > Au5 > Au11 > Au6 > Au1. Electron affinities (EAs) of Aun clusters exhibit oscillatory pattern with the cluster size. Binding energies of Aun-L complexes are oscillatory as well following EAs of Aun clusters. BEs of odd and even Aun-L complexes were analyzed separately. The bonding mechanism in odd Aun-L complexes is dominated by the lone pair -> metal electron donation to the singly occupied valence Aun orbital accompanied by the back-donation. Even Aun clusters create covalent Aun-L bonds with BEs higher than those in odd Aun-L complexes. The BEs pattern and optimized geometries of Aun-L complexes correspond to the picture of creating the gold-ligand bond through the lone pair of a ligand interacting with the singly occupied molecular orbital in odd clusters or lowest unoccupied molecular orbital in even clusters of Aun. Ligands in both odd and even Aun-L complexes form three groups with binding energies that correlate with their ionization energies. The lowest BE is calculated for H2O as a ligand, followed by SH2 and NH3. PX3 ligands exhibit highest BEs. PMID- 27187632 TI - Androgens and androgenic activity in broiler manure assessed by means of chemical analyses and in vitro bioassays. AB - The use of manure as an agricultural amendment is increasing the release of steroid hormones into the environment. Most research in this field has focused on estrogenic phenomena, with less attention paid to androgenic substances. The present study assessed androgenic activity in broiler manure using in vitro approaches based on cells stably transfected with androgen receptor. Leaching experiments were also performed to observe whether endocrine disruptors present in manure pass through a soil column and potentially reach groundwater. In parallel, an analytical chemistry method was used to determine the contribution of the most important natural androgens to androgenicity. Samplings were performed at 4 farms in 2 seasons. All but 2 samples showed androgen activity. In leakage experiments, however, no androgenic activity was detectable in leachates or in soils after leaching. According to the analytical results, androgenicity can be attributed mainly (but not completely) to androstenedione, and dihydrotestosterone. Similarly to the bioassays, chemical analysis did not reveal the presence of any androgen in leachates or soils. These results point to a rapid degradation of the substances responsible for androgenic activity in soils under the experimental conditions of the present study. However, the long-term effects associated with the constant and intensive application of manure to agricultural land require further attention. Environ Toxicol Chem 2017;36:1746 1754. (c) 2016 SETAC. PMID- 27187635 TI - Does C-reactive protein monitoring after colorectal resection with anastomosis give any practical benefit for patients with intra-abdominal septic complications? AB - AIM: This study aimed to assess the influence of the C-reactive protein (CRP) level on the early outcome after elective colorectal resection. METHOD: Patients with colorectal cancer operated on between 2006 and 2013 were identified retrospectively. They were divided into a study group operated on between 2010 and 2013 when CRP was measured routinely on the fourth postoperative day and a control group operated on between 2006 and 2009 when the CRP level was not measured routinely. Mortality, intra-abdominal septic complications (IASC), abscesses and anastomotic leakage (AL), the need for reoperation, the interval from index surgery to relaparotomy, length of hospital stay and imaging studies were compared by multivariate analysis. RESULTS: A total of 1189 patients were assessed, including 598 (50.3%) in the study group (mean age 61.3 +/- 13 years; 282 female) and 591 (49.7%) in the control group (mean age 61.8 +/- 11 years; 267 female). There were seven (1.2%) postoperative deaths in the study group and nine (1.5%) in the control group (P = 0.598). Abdominal ultrasound (US) was performed more often in the study group [97 (16.2%) vs 71 (12.0%); P = 0.037]. In the study group the interval to diagnosis of IASC was shorter than in the control group (5.7 +/- 1.5 days vs 7.3 +/- 1.3 days; P = 0.029). The decision to reoperate was also made earlier in the study group (6.2 +/- 1.7 days vs 7.4 +/- 2.8 days; P = 0.043). CONCLUSION: Routine measurement of CRP can help to make an earlier diagnosis of IASC and earlier decision for relaparotomy, without any influence on mortality or length of hospital stay. PMID- 27187634 TI - Total Synthesis of Delta(12) -Prostaglandin J3 : Evolution of Synthetic Strategies to a Streamlined Process. AB - The total synthesis of Delta(12) -prostaglandin J3 (Delta(12) -PGJ3 , 1), a reported leukemia stem cell ablator, through a number of strategies and tactics is described. The signature cross-conjugated dienone structural motif of 1 was forged by an aldol reaction/dehydration sequence from key building blocks enone 13 and aldehyde 14, whose lone stereocenters were generated by an asymmetric Tsuji-Trost reaction and an asymmetric Mukaiyama aldol reaction, respectively. During this program, a substituent-governed regioselectivity pattern for the Rh catalyzed C-H functionalization of cyclopentenes and related olefins was discovered. The evolution of the synthesis of 1 from the original strategy to the final streamlined process proceeded through improvements in the construction of both fragments 13 and 14, exploration of the chemistry of the hitherto underutilized chiral lactone synthon 57, and a diastereoselective alkylation of a cyclopentenone intermediate. The described chemistry sets the stage for large scale production of Delta(12) -PGJ3 and designed analogues for further biological and pharmacological studies. PMID- 27187637 TI - Structural analysis of an active fungal PRC2. AB - Crystal structure determination of an active polycomb repressive complex 2 (PRC2) from a thermophilic fungus, Chaetomium thermophilum, revealed some long-sought structural mechanisms for assembly, catalysis, and regulation of this important enzyme complex, responsible for trimethylation of histone H3K27 (H3K27me3) and silencing of developmentally regulated genes. In light of the crystal structures of the fungal PRC2 captured in the basal and H3K27me3-stimulated states as well as the structural analysis published previously, (1) we examined surface conservation and electrostatic potential distribution to provide additional insights into functional similarity and divergence between the fungal and human PRC2 and for PRC2 binding by nucleic acids. Structure comparison indicated a conformational change of the catalytic SET domain within PRC2 during transition from the inactive to active state. This conserved structural mechanism is also used by another histone methyltransferase family associated with gene activation for enzyme regulation and may underlie the allosteric stimulation of PRC2 as well. PMID- 27187639 TI - Hemophagocytic Lymphohistiocytosis With Secondary Atrioventricular Block Type II in a Child. PMID- 27187661 TI - Spin Frustration and Magnetic Ordering from One-Dimensional Stacking of Cr3 Triangles in TiCrIr2B2. AB - Spin-frustrated chains of Cr3 triangles are found in the new metal boride TiCrIr2B2 by synergistic experimental and theoretical investigations. Although magnetic ordering is found at 275 K, competing ferro- and anti-ferromagnetic interactions coupled with spin frustration induce a rather small total magnetic moment (0.05 MUB at 5 T), and density functional theory (DFT) calculations propose a canted, nonlinear magnetic ground-state ordering in the new phase. TiCrIr2B2 crystallizes in the hexagonal Ti1+xOs2-xRuB2 structure type (space group P62m, No. 189, Pearson symbol hP18). The structure contains trigonal planar B4 boron fragments with B-B distances of 1.76(3) A alternating along the c direction with Cr3 triangles with intra- and intertriangle Cr-Cr distances of 2.642(9) and 3.185(1) A, respectively. Magnetization measurements of TiCrIr2B2 reveal ferrimagnetic behavior and a large, negative Weiss constant of -750 K. DFT calculations demonstrate a strong site preference of Cr for the triangle sites, as well as magnetic frustration due to indirect anti-ferromagnetic interactions within the Cr3 triangles. PMID- 27187638 TI - Scaffold Diversity Synthesis and Its Application in Probe and Drug Discovery. AB - Scaffold diversity is a crucial feature of compound collections that has a huge impact on their success in biological screenings. The synthesis of highly complex and diverse scaffolds, which could be based on natural products, for example, is an arduous task that requires expertise in various aspects of organic synthesis and structural analysis. This challenge has been addressed by a number of synthesis designs, which employ natural products as a source of scaffold diversity, transform suitably designed common intermediates into various molecular frameworks, or entail highly concise synthetic routes to a number of distinct and complex scaffolds. In this Minireview, we highlight recent synthetic developments towards the construction of diverse and complex scaffolds and the application of the resulting compound collections in drug and probe discovery. PMID- 27187662 TI - Influence of the cytochrome P450 2D6 *10/*10 genotype on the pharmacokinetics of paroxetine in Japanese patients with major depressive disorder: a population pharmacokinetic analysis. AB - OBJECTIVE: Although the reduced function of the cytochrome P450 2D6*10 (CYP2D6*10) allele is common among Asian populations, existing evidence does not support paroxetine therapy adjustments for patients who have the CYP2D6*10 allele. In this study, we attempted to evaluate the degree of the impact of different CYP2D6 genotypes on the pharmacokinetic (PK) variability of paroxetine in a Japanese population using a population PK approach. METHODS: This retrospective study included 179 Japanese patients with major depressive disorder who were being treated with paroxetine. CYP2D6*1, *2, *5, *10, and *41 polymorphisms were observed. A total of 306 steady-state concentrations for paroxetine were collected from the patients. A nonlinear mixed-effects model identified the apparent Michaelis-Menten constant (Km) and the maximum velocity (Vmax) of paroxetine; the covariates included CYP2D6 genotypes, patient age, body weight, sex, and daily paroxetine dose. RESULTS: The allele frequencies of CYP2D6*1, *2, *5, *10, and *41 were 39.4, 14.5, 4.5, 41.1, and 0.6%, respectively. There was no poor metabolizer who had two nonfunctional CYP2D6*5 alleles. A one-compartment model showed that the apparent Km value was decreased by 20.6% in patients with the CYP2D6*10/*10 genotype in comparison with the other CYP2D6 genotypes. Female sex also influenced the apparent Km values. No PK parameters were affected by the presence of one CYP2D6*5 allele. CONCLUSION: Unexpectedly, elimination was accelerated in individuals with the CYP2D6*10/*10 genotype. Our results show that the presence of one CYP2D6*5 allele or that of any CYP2D6*10 allele may have no major effect on paroxetine PKs in the steady state. PMID- 27187663 TI - Human dihydrofolate reductase and thymidylate synthase form a complex in vitro and co-localize in normal and cancer cells. AB - Enzymes involved in thymidylate biosynthesis, thymidylate synthase (TS), and dihydrofolate reductase (DHFR) are well-known targets in cancer chemotherapy. In this study, we demonstrated for the first time, that human TS and DHFR form a strong complex in vitro and co-localize in human normal and colon cancer cell cytoplasm and nucleus. Treatment of cancer cells with methotrexate or 5 fluorouracil did not affect the distribution of either enzyme within the cells. However, 5-FU, but not MTX, lowered the presence of DHFR-TS complex in the nucleus by 2.5-fold. The results may suggest the sequestering of TS by FdUMP in the cytoplasm and thereby affecting the translocation of DHFR-TS complex to the nucleus. Providing a strong likelihood of DHFR-TS complex formation in vivo, the latter complex is a potential new drug target in cancer therapy. In this paper, known 3D structures of human TS and human DHFR, and some protozoan bifunctional DHFR-TS structures as templates, are used to build an in silico model of human DHFR-TS complex structure, consisting of one TS dimer and two DHFR monomers. This complex structure may serve as an initial 3D drug target model for prospective inhibitors targeting interfaces between the DHFR and TS enzymes. PMID- 27187665 TI - A review of principles in design and usability testing of tactile technology for individuals with visual impairments. AB - To lay the groundwork for devising, improving, and implementing new technologies to meet the needs of individuals with visual impairments, a systematic literature review was conducted to: a) describe hardware platforms used in assistive devices, b) identify their various applications, and c) summarize practices in user testing conducted with these devices. A search in relevant EBSCO databases for articles published between 1980 and 2014 with terminology related to visual impairment, technology, and tactile sensory adaptation yielded 62 articles that met the inclusion criteria for final review. It was found that while earlier hardware development focused on pin matrices, the emphasis then shifted toward force feedback haptics and accessible touch screens. The inclusion of interactive and multimodal features has become increasingly prevalent. The quantity and consistency of research on navigation, education, and computer accessibility suggest that these are pertinent areas of need for the visually impaired community. Methodologies for usability testing ranged from case studies to larger cross-sectional studies. Many studies used blindfolded sighted users to draw conclusions about design principles and usability. Altogether, the findings presented in this review provide insight on effective design strategies and user testing methodologies for future research on assistive technology for individuals with visual impairments. PMID- 27187664 TI - Different pattern of viral infections and clinical outcomes in patient with acute exacerbation of chronic obstructive pulmonary disease and chronic obstructive pulmonary disease with pneumonia. AB - Respiratory viruses are well-known causes of acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) and also important pathogens for concomitant pneumonia in COPD (CP-COPD). However, the differences in a viral infection pattern and clinical impacts of respiratory viruses between the two groups have not been well investigated. The clinical and microbiological data from COPD patients admitted with AE-COPD (n = 281) or CP-COPD (n = 284) between January 2010 and December 2012 were reviewed. After excluding 88 patients (40 with AE-COPD and 48 with CP-COPD) who did not undergo a multiplex RT-PCR test for respiratory viruses, the demographic characteristics, identified viruses, and clinical outcomes of the AE-COPD and CP-COPD groups were compared. Respiratory viruses were identified in 41.9% of AE-COPD group and 33.5% of the CP-COPD groups. The most common virus was influenza virus in the AE-COPD group (33.7%) versus human coronavirus (24.1%) in the CP-COPD group. Influenza virus was significantly more common in the AE-ACOPD group than in the CP-COPD group (P < 0.01). In-hospital mortality of AE-COPD and CP-COPD were 1.2% and 12.3%, respectively (P < 0.01). Among CP-COPD patients, in-hospital mortality of patients with only viral infection group, only bacterial infection group, and viral-bacterial co-infection were 2.6%, 25.8%, and 17.5%, respectively (P = 0.01). Respiratory viruses were commonly identified in both AE-COPD and CP-COPD, influenza virus and human coronavirus were the most common viruses identified in AE-COPD and CP-COPD patients, respectively. The mortality rates of only viral infection group was significantly lower than only bacterial infection or viral bacterial co-infection group in CP-COPD patients. J. Med. Virol. 88:2092-2099, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27187666 TI - Successful treatment of perianal condylomata acuminata with ingenol mebutate gel. PMID- 27187679 TI - Correction to: Infection in cystic fibrosis: impact of the environment and climate. PMID- 27187667 TI - Simultaneous Hosting of Positive and Negative Trions and the Enhanced Direct Band Emission in MoSe2/MoS2 Heterostacked Multilayers. AB - Heterostacking of layered transition-metal dichalcogenide (LTMD) monolayers (1Ls) offers a convenient way of designing two-dimensional exciton systems. Here we demonstrate the simultaneous hosting of positive trions and negative trions in heterobilayers made by vertically stacking 1L MoSe2 and 1L MoS2. The charge transfer occurring between the 1Ls of MoSe2 and MoS2 converted the polarity of trions in 1L MoSe2 from negative to positive, resulting in the presence of positive trions in the 1L MoSe2 and negative trions in the 1L MoS2 of the same heterostacked bilayer. Significantly enhanced MoSe2 photoluminescence (PL) in the heterostacked bilayers compared to the PL of 1L MoSe2 alone suggests that, unlike other previously reported heterostacked bilayers, direct band transition of 1L MoSe2 in heterobilayer was enhanced after the vertical heterostacking. Moreover, by inserting hexagonal BN monolayers between 1L MoSe2 and 1L MoS2, we were able to adjust the charge transfer to maximize the MoSe2 PL of the heteromultilayers and have achieved a 9-fold increase of the PL emission. The enhanced optical properties of our heterostacked LTMDs suggest the exciting possibility of designing LTMD structures that exploit the superior optical properties of 1L LTMDs. PMID- 27187680 TI - Bridging the schism of schizophrenia through yoga-Review of putative mechanisms. AB - Schizophrenia patients experience a 'disconnect' at multiple levels-neuronal networks, mental processes, and interpersonal relationships. The resultant poor quality-of-life and functional disability are related to the persistent cognitive deficits and negative symptoms, which are rather resistant to conventional antipsychotic medications. Yoga has emerged as an important therapeutic intervention to improve quality-of-life in schizophrenia. Recent preliminary evidence suggests that effects of yoga on cognitive and negative symptoms may drive this benefit. This study attempts to integrate evidence from neuroscience based research, which focuses on the neuroplasticity-harnessing effects of yoga to bridge the schizophrenia connectopathy. In an overarching model to study putative neurobiological mechanisms that drive therapeutic effects of yoga, it is proposed that (a) various styles of meditation may help in strengthening the lateral and medial prefrontal brain networks, thus improving neurocognition and mentalizing abilities, and (b) learning and performing co-ordinated physical postures with a teacher facilitates imitation and the process of being imitated, which can improve social cognition and empathy through reinforcement of the premotor and parietal mirror neuron system. Oxytocin may play a role in mediating these processes, leading to better social connectedness and social outcomes. Clinical and heuristic implications of this model are further discussed. PMID- 27187681 TI - Emerging Applications of Abdominal 4D Flow MRI. AB - OBJECTIVE: Comprehensive assessment of abdominal hemodynamics is crucial for many clinical diagnoses but is challenged by a tremendous complexity of anatomy, normal physiology, and a wide variety of pathologic abnormalities. This article introduces 4D flow MRI as a powerful technique for noninvasive assessment of the hemodynamics of abdominal vascular territories. CONCLUSION: Four-dimensional flow MRI provides clinicians with a more extensive and straightforward approach to evaluate disorders that affect blood flow in the abdomen. This review presents a series of clinical cases to illustrate the utility of 4D flow MRI in the comprehensive assessment of the abdominal circulation. PMID- 27187683 TI - Loss of N-acetylgalactosaminyltransferase 3 in poorly differentiated pancreatic cancer: augmented aggressiveness and aberrant ErbB family glycosylation. AB - BACKGROUND: Aberrant glycosylation of several proteins underlie pancreatic ductal adenocarcinoma (PDAC) progression and metastasis. O-glycosylation is initiated by a family of enzymes known as polypeptide N-acetylgalactosaminyl transferases (GalNAc-Ts/GALNTs). In this study, we investigated the role of the O glycosyltransferase GALNT3 in PDAC. METHODS: Immunohistochemistry staining of GALNT3 was performed on normal, inflammatory and neoplastic pancreatic tissues. Several in vitro functional assays such as proliferation, colony formation, migration and tumour-endothelium adhesion assay were conducted in GALNT3 knockdown PDAC cells to investigate its role in disease aggressiveness. Expression of signalling molecules involved in growth and motility was evaluated using western blotting. Effect of GALNT3 knockdown on glycosylation was examined by lectin pull-down assay. RESULTS: N-acetylgalactosaminyl transferase 3 expression is significantly decreased in poorly differentiated PDAC cells and tissues as compared with well/moderately differentiated PDAC. Further, knockdown of GALNT3 resulted in increased expression of poorly differentiated PDAC markers, augmented growth, motility and tumour-endothelium adhesion. Pull-down assay revealed that O-glycans (Tn and T) on EGFR and Her2 were altered in PDAC cells, which was accompanied by their increased phosphorylation. CONCLUSIONS: Our study indicates that loss of GALNT3 occurs in poorly differentiated PDAC, which is associated with the increased aggressiveness and altered glycosylation of ErbB family proteins. PMID- 27187684 TI - A population-based analysis of secondary malignancies in breast cancer patients receiving breast reconstruction. AB - BACKGROUND: There is an ongoing debate about the relationship between breast implants and secondary malignancies. METHODS: Breast cancer patients undergoing surgical reconstruction after mastectomy by either implants or autologous flap were identified in the Surveillance, Epidemiology and End Results registry between 1998 and 2002. The occurrence of secondary malignancies at least 1 year after diagnosis was compared between breast reconstruction with implants vs autologous flap. RESULTS: Of 7955 women, 3727 underwent reconstruction using implants and 4228 using autologous flap. The incidence of secondary tumours was similar in both the groups (hazards ratio (HR)=1.02, 95% confidence interval (CI): 0.82-1.26, P=0.880). For lung cancer, a significantly increased risk for implants (HR=2.51, 95% CI: 1.28-4.95, P=0.005) was observed. CONCLUSIONS: Except for lung cancer, no association between implants and secondary malignancies including lymphomas was observed. PMID- 27187682 TI - The search for true numbers of neurons and glial cells in the human brain: A review of 150 years of cell counting. AB - For half a century, the human brain was believed to contain about 100 billion neurons and one trillion glial cells, with a glia:neuron ratio of 10:1. A new counting method, the isotropic fractionator, has challenged the notion that glia outnumber neurons and revived a question that was widely thought to have been resolved. The recently validated isotropic fractionator demonstrates a glia:neuron ratio of less than 1:1 and a total number of less than 100 billion glial cells in the human brain. A survey of original evidence shows that histological data always supported a 1:1 ratio of glia to neurons in the entire human brain, and a range of 40-130 billion glial cells. We review how the claim of one trillion glial cells originated, was perpetuated, and eventually refuted. We compile how numbers of neurons and glial cells in the adult human brain were reported and we examine the reasons for an erroneous consensus about the relative abundance of glial cells in human brains that persisted for half a century. Our review includes a brief history of cell counting in human brains, types of counting methods that were and are employed, ranges of previous estimates, and the current status of knowledge about the number of cells. We also discuss implications and consequences of the new insights into true numbers of glial cells in the human brain, and the promise and potential impact of the newly validated isotropic fractionator for reliable quantification of glia and neurons in neurological and psychiatric diseases. J. Comp. Neurol. 524:3865-3895, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27187685 TI - Levels of matrix metalloproteinases differ in plasma and serum - aspects regarding analysis of biological markers in cancer. AB - BACKGROUND: There are inconsistencies in the use of serum or plasma when analysing the matrix metalloproteinases (MMPs) as diagnostic or prognostic markers. The purpose of this study was to compare the concentration of MMP-1, -2, -7, -8, -9 and -13 in serum vs plasma samples. METHODS: Blood samples were obtained from sixty-five men and women. Samples were analysed for levels of MMPs in corresponding citrate plasma and serum. RESULTS: All MMPs expressed higher concentration in serum compared with plasma (P<0.01). There were no differences between genders. CONCLUSIONS: Present study demonstrated significant differences regarding concentrations of some MMPs using plasma vs serum. We conclude that future studies regarding MMPs as biological markers in cancer should consider the use of citrate plasma instead of serum. PMID- 27187686 TI - MED12 mutations and FH inactivation are mutually exclusive in uterine leiomyomas. AB - BACKGROUND: Uterine leiomyomas from hereditary leiomyomatosis and renal cell cancer (HLRCC) patients are driven by fumarate hydratase (FH) inactivation or occasionally by mediator complex subunit 12 (MED12) mutations. The aim of this study was to analyse whether MED12 mutations and FH inactivation are mutually exclusive and to determine the contribution of MED12 mutations on HLRCC patients' myomagenesis. METHODS: MED12 exons 1 and 2 mutation screening and 2SC immunohistochemistry indicative for FH deficiency was performed on a comprehensive series of HLRCC patients' (122 specimens) and sporadic (66 specimens) tumours. Gene expression analysis was performed using Affymetrix GeneChip Human Exon Arrays (Affymetrix, Santa Clara, CA, USA). RESULTS: Nine tumours from HLRCC patients harboured a somatic MED12 mutation and were negative for 2SC immunohistochemistry. All remaining successfully analysed lesions (107/116) were deficient for FH. Of sporadic tumours, 35/64 were MED12 mutation positive and none displayed a FH defect. In global gene expression analysis FH deficient tumours clustered together, whereas HLRCC patients' MED12 mutation positive tumours clustered together with sporadic MED12 mutation-positive tumours. CONCLUSIONS: Somatic MED12 mutations and biallelic FH inactivation are mutually exclusive in both HLRCC syndrome-associated and sporadic uterine leiomyomas. The great majority of HLRCC patients' uterine leiomyomas are caused by FH inactivation, but incidental tumours driven by somatic MED12 mutations also occur. These MED12 mutation-positive tumours display similar expressional profiles with their sporadic counterparts and are clearly separate from FH deficient tumours. PMID- 27187687 TI - A nomogram for predicting complications in patients with solid tumours and seemingly stable febrile neutropenia. AB - BACKGROUND: We sought to develop and externally validate a nomogram and web-based calculator to individually predict the development of serious complications in seemingly stable adult patients with solid tumours and episodes of febrile neutropenia (FN). PATIENTS AND METHODS: The data from the FINITE study (n=1133) and University of Salamanca Hospital (USH) FN registry (n=296) were used to develop and validate this tool. The main eligibility criterion was the presence of apparent clinical stability, defined as events without acute organ dysfunction, abnormal vital signs, or major infections. Discriminatory ability was measured as the concordance index and stratification into risk groups. RESULTS: The rate of infection-related complications in the FINITE and USH series was 13.4% and 18.6%, respectively. The nomogram used the following covariates: Eastern Cooperative Group (ECOG) Performance Status ?2, chronic obstructive pulmonary disease, chronic cardiovascular disease, mucositis of grade ?2 (National Cancer Institute Common Toxicity Criteria), monocytes <200/mm(3), and stress-induced hyperglycaemia. The nomogram predictions appeared to be well calibrated in both data sets (Hosmer-Lemeshow test, P>0.1). The concordance index was 0.855 and 0.831 in each series. Risk group stratification revealed a significant distinction in the proportion of complications. With a ?116-point cutoff, the nomogram yielded the following prognostic indices in the USH registry validation series: 66% sensitivity, 83% specificity, 3.88 positive likelihood ratio, 48% positive predictive value, and 91% negative predictive value. CONCLUSIONS: We have developed and externally validated a nomogram and web calculator to predict serious complications that can potentially impact decision making in patients with seemingly stable FN. PMID- 27187690 TI - Preterm Birth, Age at School Entry and Long Term Educational Achievement. AB - OBJECTIVE: To investigate if the detrimental impact of year of entering education in preterm infants persists into adolescence. BACKGROUND: Preterm infants are often enrolled in school a year earlier than would be expected if this decision is based on their actual date of birth rather than their due date. Initially these infants appear to do disproportionately worse than those who do not 'skip' a year. However, it is unclear if this effect remains as the infants grow, to have an important effect on long term achievements in education. DESIGN: A cohort study, drawn from the Avon Longitudinal Study of Parents and Children (ALSPAC). The exposure measurement was gestational age (defined as preterm (<37 weeks gestation) or term (37-42 weeks)). The primary outcome was a low score at the Key Stage 4 (KS4) educational assessment or receiving special educational needs support (both at age 16). We derived conditional regression models matching preterm to term infants on their date of birth (DOB), their expected date of delivery (EDD), or their expected date of delivery and year of school entry. RESULTS: After matching for DOB, preterm infants had an increased odds of SEN (OR 1.57 (1.33-1.86)) and the association remained after adjusting for potential confounders (OR 1.39 (1.14-1.68)). The association remained in the analysis matching for EDD (fully adjusted OR 1.43 (1.17-1.74)) but attenuated after restricting to those infants who were enrolled in school in the same year as the control infants (fully adjusted OR 1.21 (0.97-1.52)). There was less evidence for an impact of prematurity on the KS4 score (Matched for DOB; OR 1.10 (0.91 to 1.34), matched for EDD OR 1.17 (0.96 to 1.42) and EDD and same year of schooling, OR 1.00 (0.80 to 1.26)). CONCLUSIONS: This modifiable effect of going to school a year earlier than predicted by their due date appears to have measurable consequences for ex-preterm infants in adolescence and is likely to limit adulthood opportunities. PMID- 27187689 TI - Sticky Genomes: Using NGS Evidence to Test Hybrid Speciation Hypotheses. AB - Hypotheses of hybrid origin are common. Here we use next generation sequencing to test a hybrid hypothesis for a non-model insect with a large genome. We compared a putative hybrid triploid stick insect species (Acanthoxyla geisovii) with its putative paternal diploid taxon (Clitarchus hookeri), a relationship that provides clear predictions for the relative genetic diversity within each genome. The parental taxon is expected to have comparatively low allelic diversity that is nested within the diversity of the hybrid daughter genome. The scale of genome sequencing required was conveniently achieved by extracting mRNA and sequencing cDNA to examine expressed allelic diversity. This allowed us to test hybrid progenitor relationships among non-model organisms with large genomes and different ploidy levels. Examination of thousands of independent loci avoids potential problems produced by the silencing of parts of one or other of the parental genomes, a phenomenon sometimes associated with the process of stabilisation of a hybrid genome. Transcript assembles were assessed for evidence of paralogs and/or alternative splice variants before proceeding. Comparison of transcript assemblies was not an appropriate measure of genetic variability, but by mapping reads back to clusters derived from each species we determined levels of allelic diversity. We found greater cDNA sequence diversity among alleles in the putative hybrid species (Acanthoxyla geisovii) than the non-hybrid. The allelic diversity within the putative paternal species (Clitachus hookeri) nested within the hybrid-daughter genome, supports the current view of a hybrid progenitor relationship for these stick insect species. Next generation sequencing technology provides opportunities for testing evolutionary hypotheses with non-model organisms, including, as here, genomes that are large due to polyploidy. PMID- 27187692 TI - Erratum. PMID- 27187688 TI - Telmisartan Modulates Glial Activation: In Vitro and In Vivo Studies. AB - The circulating renin-angiotensin system (RAS), including the biologically active angiotensin II, is a fundamental regulatory mechanism of blood pressure conserved through evolution. Angiotensin II components of the RAS have also been identified in the brain. In addition to pro-inflammatory cytokines, neuromodulators, such as angiotensin II can induce (through angiotensin type 1 receptor (AT1R)) some of the inflammatory actions of brain glial cells and influence brain inflammation. Moreover, in Alzheimer's disease (AD) models, where neuroinflammation occurs, increased levels of cortical AT1Rs have been shown. Still, the precise role of RAS in neuroinflammation is not completely clear. The overall aim of the present study was to elucidate the role of RAS in the modulation of glial functions and AD pathology. To reach this goal, the specific aims of the present study were a. to investigate the long term effect of telmisartan (AT1R blocker) on tumor necrosis factor-alpha (TNF-alpha), interleukin 1-beta (IL1-beta) and nitric oxide (NO) release from glial cells. b. to examine the effect of intranasally administered telmisartan on amyloid burden and microglial activation in 5X familial AD (5XFAD) mice. Telmisartan effects in vivo were compared to those of perindopril (angiotensin converting enzyme inhibitor). Long-term-exposure of BV2 microglia to telmisartan significantly decreased lipopolysaccharide (LPS) induced NO, inducible NO synthase, TNF-alpha and IL1-beta synthesis. The effect of Telmisartan on NO production in BV2 cells was confirmed also in primary neonatal rat glial cells. Intranasal administration of telmisartan (1 mg/kg/day) for up to two months significantly reduced amyloid burden and CD11b expression (a marker for microglia) both in the cortex and hipoccampus of 5XFAD. Based on the current view of RAS and our data, showing reduced amyloid burden and glial activation in the brains of 5XFAD transgenic mice, one may envision potential intervention with the progression of glial activation and AD by using AT1R blockers. PMID- 27187691 TI - Farming, Foreign Holidays, and Vitamin D in Orkney. AB - Orkney, north of mainland Scotland, has the world's highest prevalence of multiple sclerosis (MS); vitamin D deficiency, a marker of low UV exposure, is also common in Scotland. Strong associations have been identified between vitamin D deficiency and MS, and between UV exposure and MS independent of vitamin D, although causal relationships remain to be confirmed. We aimed to compare plasma 25-hydroxyvitamin D levels in Orkney and mainland Scotland, and establish the determinants of vitamin D status in Orkney. We compared mean vitamin D and prevalence of deficiency in cross-sectional study data from participants in the Orkney Complex Disease Study (ORCADES) and controls in the Scottish Colorectal Cancer Study (SOCCS). We used multivariable regression to identify factors associated with vitamin D levels in Orkney. Mean (standard deviation) vitamin D was significantly higher among ORCADES than SOCCS participants (35.3 (18.0) and 31.7 (21.2), respectively). Prevalence of severe vitamin D deficiency was lower in ORCADES than SOCCS participants (6.6% to 16.2% p = 1.1 x 10(-15)). Older age, farming occupations and foreign holidays were significantly associated with higher vitamin D in Orkney. Although mean vitamin D levels are higher in Orkney than mainland Scotland, this masks variation within the Orkney population which may influence MS risk. PMID- 27187693 TI - Screening and identification of Caulis Sinomenii bioactive ingredients with dual target NF-kappaB inhibition and beta2- AR agonizing activities. AB - Caulis Sinomenii (CS) is a valuable traditional medicine in China. Its extract can act as an anti-inflammatory agent and a vascular smooth muscle relaxant. However, the underlying mechanisms remain unknown. In this study, we developed a simple dual-target method based on ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry combined with a dual target bioactive screening assay for anti-inflammatory and antispasmodic activities to characterize the chemical structure of various bioactive compounds of CS rapidly. Seven potential NF-kappaB inhibitors were identified, including laudanosoline-1-O-xylopyranose, 6-O-methyl-laudanosoline-1-O-glucopyranoside, menisperine, sinomenine, laurifoline, magnoflorine and norsinoacutin. Furthermore, IL-6 and IL-8 assays confirmed the anti-inflammatory effects of these potential NF-kappaB inhibitors, in which laudanosoline-1-O-d-xylopyranose and menisperine were revealed as novel NF-kappaB inhibitors. Among the seven identified alkaloids, three potential beta2 -adrenergic receptor agonists, including sinomenine, magnoflorine and laurifoline, were characterized using a luciferase reporter system to measure for the activity of beta2 -adrenergic receptor agonists. Finally, sinomenine, magnoflorine and laurifoline were identified not only as potential NF-kappaB inhibitors but also as potential beta2 -adrenegic receptor agonists, which is the first time this has been reported. Molecular dynamic simulation and docking results suggest that the three dual bioactive constituents could not only inhibit Pseudomonas aeruginosa PAK strain induced inflammatory responses via a negative regulation of the Braf protein that participates in MAPK signaling pathway but also activate the beta2 -adrenegic receptor. These results suggest that CS extract has dual signaling activities with potential clinical application as a novel drug for asthma. PMID- 27187694 TI - [Cognitive and social skills are necessary for safe teamwork]. AB - Most safety-critical enterprises have programs for teaching and training non technical skills to their employees. These skills must complement pure technical skills. Programs for teaching and introducing these skills (communication, leadership, teamwork, decision-making, handling of conflicts and feed-back) are developing also in health-care. It is important that non-technical skills in combination with technical skills are seen as the foundation when developing new and safer ways to do the daily work with patients. PMID- 27187695 TI - [Telephone referrals to the emergency department behind a large part of the visits. 4 out of 5 have health care contact prior to visits to the emergency department]. AB - For unknown reasons, the number of visits to Swedish A&E Departments is on the increase. This study was designed to research whether patients had been in contact with the health service prior to their visit to the Orebro University Hospital A&E Department and if so, which part of the healthcare system. Our study revealed that 80% of patients had been in contact with the healthcare service prior to their visit, that referrals by telephone constituted a large proportion of visits and that the level of medical seriousness differed between the various methods of referral. PMID- 27187696 TI - [Glycocalyx is an active part of the endothelium]. AB - The inner side of the endothelium is covered by a thin layer of glycosylated proteins called the glycocalyx, which binds plasma to its surface up to a total thickness of 1-3 um. The glycocalyx governs the endothelial permeability for macromolecules and has a key role in the regulation of microvascular perfusion. The glycocalyx also prevents adhesion of thrombocytes to the endothelial surface and counteracts microthrombosis by harbouring antithrombin III and thrombomodulin in its plasma layer. Knowledge about the ultrastructure of the glycocalyx has resulted in a revision of the Starling equation, which currently takes little notice of the oncotic pressure of the interstitial fluid space. The glycocalyx is involved in the initiation of the inflammatory response and is easily broken down (shedded) in response to sepsis, trauma, surgery, and cardiovascular disease. A shedded glycocalyx layer seems to impair the prognosis of heart failure and kidney disease. Its role as a mediator of cardiovascular complications to chronic disease is currently an important research topic. PMID- 27187698 TI - [In Process Citation]. PMID- 27187697 TI - [Rheumatic heart disease behind life-threatening heart failure in pregnancy]. AB - Valvular heart disease constitutes the majority of all causes of heart disease in pregnancy. In the presence of valvular heart disease, the necessary haemodynamic changes of pregnancy might cause heart failure, leading to severe maternal and fetal morbidity and even mortality. In lower-income countries, rheumatic heart disease remains one of the major causes of death related to pregnancy [6]. In low income countries, rheumatic heart disease is found in 60% to 80% of the pregnant women with heart disease, and 10% to 30% have a congenital disorder including congenital valve disorders [4]. The most common valvular lesion of rheumatic heart disease is mitral stenosis. This valvular lesion can be the cause of extreme disability and even mortality during pregnancy due to an increase in the transvalvular gradient and a rise in left atrial pressure. The maternal mortality associated with mitral stenosis is stratified by New York Heart Association (NYHA) classification: class I, 0.1%; class II, 0.3%; class III, 5.5%; and class IV, 6.0%. Most patients are in class I or II at presentation, but 12% to 25% of patients are in class III or IV [14]. PMID- 27187699 TI - [CPR and the right to a dignified death]. PMID- 27187700 TI - [The foundation of health problems]. PMID- 27187701 TI - [Try-out-research during the internship stimulates further research]. PMID- 27187702 TI - [Lipid A - possible effective prophylaxis? Epigenetics may lose its importance in allergy]. PMID- 27187703 TI - [The report "Efficient Care" lacks focus in the proposals]. PMID- 27187704 TI - [Report on medical age determination "a careless piece of work"]. PMID- 27187705 TI - [In Process Citation]. PMID- 27187706 TI - [In Process Citation]. PMID- 27187707 TI - [In Process Citation]. PMID- 27187708 TI - [In Process Citation]. PMID- 27187709 TI - [In Process Citation]. PMID- 27187710 TI - [In Process Citation]. PMID- 27187711 TI - [In Process Citation]. PMID- 27187712 TI - [In Process Citation]. PMID- 27187713 TI - [In Process Citation]. PMID- 27187714 TI - Impact of changing wind conditions on foraging and incubation success in male and female wandering albatrosses. AB - Wind is an important climatic factor for flying animals as by affecting their locomotion, it can deeply impact their life-history characteristics. In the context of globally changing wind patterns, we investigated the mechanisms underlying recently reported increase in body mass of a population of wandering albatrosses (Diomedea exulans) with increasing wind speed over time. We built a foraging model detailing the effects of wind on movement statistics and ultimately on mass gained by the forager and mass lost by the incubating partner. We then simulated the body mass of incubating pairs under varying wind scenarios. We tracked the frequency at which critical mass leading to nest abandonment was reached to assess incubation success. We found that wandering albatrosses behave as time minimizers during incubation as mass gain was independent of any movement statistics but decreased with increasing mass at departure. Individuals forage until their energy requirements, which are determined by their body conditions, are fulfilled. This can come at the cost of their partner's condition as mass loss of the incubating partner depended on trip duration. This behaviour is consistent with strategies of long-lived species which favoured their own survival over their current reproductive attempt. In addition, wind speed increased ground speed which in turn reduced trip duration and males foraged further away than females at high ground speed. Contrasted against an independent data set, the simulation performed satisfactorily for males but less so for females under current wind conditions. The simulation predicted an increase in male body mass growth rate with increasing wind speed, whereas females' rate decreased. This trend may provide an explanation for the observed increase in mass of males but not of females. Conversely, the simulation predicted very few nest abandonments, which is in line with the high breeding success of this species and is contrary to the hypothesis that wind patterns impact incubation success by altering foraging movement. PMID- 27187715 TI - Hepatotoxicity of targeted therapy for cancer. AB - INTRODUCTION: Understanding the mechanism of DILI with MTA, and how to avoid and manage these toxicities is essential for minimising inferior cancer treatment outcomes. An organised and comprehensive overview of MTA-associated hepatotoxicity is lacking; this review aims to fill the gap. AREAS COVERED: A literature review was performed based on published case reports and relevant studies or articles pertaining to the topics on PubMed. Food and Drug Administration drug information documents and search on the US National Library of Medicine LiverTox database was performed for all relevant MTA. EXPERT OPINION: MTA-associated hepatotoxicity is common but rarely fatal. The pattern of hepatotoxicity is predominantly idiosyncratic. Pharmacogenomics show potential in predicting patients at risk of poorly metabolising or developing immunoallergic responses to MTA, but prospective data is scant. Preventing reactivation of viral hepatitis using anti-viral drugs, and avoidance of drug combinations at high risk of negative interactions are the most readily preventable measures for DILI. PMID- 27187716 TI - EtAlCl2/2,6-Disubstituted Pyridine-Mediated Carboxylation of Alkenes with Carbon Dioxide. AB - alpha-Arylalkenes and trialkyl-substituted alkenes undergo carboxylation with CO2 in the presence of EtAlCl2 and 2,6-dibromopyridine to afford the corresponding alpha,beta- and/or beta,gamma-unsaturated carboxylic acids. This reaction is suggested to proceed via the electrophilic substitution of EtAlCl2 with the aid of the base, followed by the carbonation of the resulting ate complex. This reaction can be applied to terminal dialkylalkenes by using a mixture of 2,6-di tert-butylpyridine and 2,6-dibromopyridine. PMID- 27187718 TI - Development of transferosomal gel for trans-dermal delivery of insulin using iodine complex. AB - The main object of this current research was to examine transferosomes as a transdermal delivery system for insulin, to overwhelm the difficulties related with its subcutaneous delivery. Transferosomal gel formulations were prepared by rotary evaporation sonication technique. The result revealed that insulin was successfully entrapped (78%) in optimized formulations (2.5 I.U. of the drug and 25% of sodium cholate) with cumulative percent drug release (83.11 +/- 3.782). The glucose lowering study revealed that the transferosomal gel with chemical penetration enhancer showed better glucose lowering effect as compared to the control gel. Consequently, this study authenticated that the transferosomal gel can be used as a possible substitute to the conventional formulations of insulin with progressive permeation characteristics for transdermal application. PMID- 27187717 TI - Determining Chiral Configuration of Diamines via Contact Angle Measurements on Enantioselective Alanine-Appended Benzene-Tricarboxamide Gelators. AB - Spectroscopic techniques exist that may discern between enantiomers and assess chiral purity. A nonspectroscopic approach that may be directly observed could provide numerous benefits. Using chiral alanine-appended benzene-tricarboxamide gelators, we reveal a methanol gel system that is capable of providing visual discrimination between enantiomers of various diamines. Specifically, gelation is induced by supramolecular nanofiber assembly resulting from interaction between a chiral gelator and a diamine of opposing chirality (i.e., a heterochiral system). Upon further implementing the chiral gelator in electrospun fibers as solid state films, we revealed enantioselective surface wetting properties that allowed for determining chirality through contact angle measurements. While these two approaches of observable gelation and surface wetting offer nonspectroscopic approaches, we also find that the supramolecular nanofiber assembly was able to enhance the induced circular dichroism signal resulting from addition of chiral diamines, allowing precise quantification of their enantiomeric purity. PMID- 27187719 TI - Antireflective Coatings for Glass and Transparent Polymers. AB - Antireflective coatings (ARCs) are applied to reduce surface reflections. We review coatings that reduce the reflection of the surface of the transparent substrates float glass, polyethylene terephthalate, poly(methyl methacrylate), and polycarbonate. Three main coating concepts exist to lower the reflection at the interface of a transparent substrate and air: multilayer interference coatings, graded index coatings, and quarter-wave coatings. We introduce and discuss these three concepts, and zoom in on porous quarter-wave coatings comprising colloidal particles. We extensively discuss the four routes for introducing porosity in quarter-wave coatings through the use of colloidal particles, which have the highest potential for application: (1) packing of dense nanospheres, (2) integration of voids through hollow nanospheres, (3) integration of voids through sacrificial particle templates, and (4) packing of nonspherical nanoparticles. Finally, we address the remaining challenges in the field of ARCs, and elaborate on potential strategies for future research in this area. PMID- 27187720 TI - Review of maintenance of response to psoriasis treatments. AB - BACKGROUND: Biologics are highly effective treatments for moderate-severe psoriasis with a high percentage of patients achieving 75% improvement in Psoriasis Area Severity Index (PASI75) at 12 weeks. However, psoriasis is a chronic disease, and long-term efficacy is critical. OBJECTIVE: Long-term responses of systemic psoriasis treatments and how this effect is reported. METHODS: A PubMed literature was performed to identify studies describing long term response rates to available systemic psoriasis treatments. Within these studies, we examined how maintenance rates were reported. All studies with long term efficacy data ranging from 24 to 244 weeks were considered. RESULTS: Thirteen studies met the inclusion criteria. When comparing medications at 1 year, response rates among the initial treatment groups were best with secukinumab (65.2%) and worst with apremilast (18.7%). Among only initial responders at 10-16 weeks who received 1 year of continuous treatment, maintenance was best with adalimumab (95.2%) and worst with apremilast (61%). LIMITATIONS: The different methodologies used to report maintenance of response over time make it difficult to compare response rates across drugs studied in different trials. CONCLUSION: Long-term response rates of systemic treatment of psoriasis are high. Effect may be influenced by many factors and can be analyzed in different ways, making comparisons across different trials difficult. PMID- 27187721 TI - Resection vs. ablation for alpha-fetoprotein positive hepatocellular carcinoma within the Milan criteria: a propensity score analysis. AB - BACKGROUND & AIMS: The lack of histopathological confirmation of hepatocellular carcinoma (HCC) diagnosis for patients receiving ablation may result in misdiagnosis of benign liver nodule as HCC occasionally, contributing to false treatment efficacy. This underestimated issue is one reason why the ablation efficacy remains undetermined compared with hepatic resection. Our aim is to compare the efficacy of ablation and resection for HCC within the Milan criteria after excluding the impact of misdiagnosis. METHODS: Alpha-fetoprotein > 200 ng/ml was introduced as an inclusion criterion to improve diagnosis accuracy. A total of 435 (resection, 310; ablation, 125) HCC patients within the Milan criteria and without portal hypertension were enrolled. Propensity score matching analysis identified 259 (resection, 150; ablation, 109) patients to compare treatment efficacy. RESULTS: Before matching, the survival of resection group were superior to ablation group with 5-year overall survival (OS) rate of 77.6% vs. 53.8% (P < 0.001), respectively, and 5-year recurrence-free survival (RFS) rate of 57.2% vs. 29.1% (P < 0.001) respectively. After matching, the baseline was well-balanced between the two groups. The 5-year OS rates were 71.5% vs. 51.3% (P < 0.001), and 5-year RFS rates were 56.1% vs. 25.6% (P < 0.001) for the resection and ablation groups respectively. Cox regression analysis identified ablation as an independent predictor for mortality and tumour recurrence (HR: 2.123 and 2.308, respectively; both P < 0.01). CONCLUSIONS: Hepatic resection provides better OS and RFS than ablation for alpha-fetoprotein positive HCC patients within the Milan criteria and without portal hypertension. PMID- 27187723 TI - Correspondence: On the nature of strong piezoelectricity in graphene on SiO2. PMID- 27187724 TI - Making the Least Reactive Electrophile the First in Class: Domino Electrophilic Activation of Amides. AB - The electrophilic activation of amides, especially by the action of trifluoromethanesulfonic (triflic) anhydride, enables the formation of highly electrophilic and reactive intermediates, lending themselves to diverse reaction pathways. This synopsis sets out to highlight recent advances in the field of amide activation, focused on the use of triflic anhydride, and the myriad of transformations that can ensue upon addition of several classes of electrophiles to the intermittently generated high energy intermediates. PMID- 27187722 TI - A Novel Mutant Allele of Pw1/Peg3 Does Not Affect Maternal Behavior or Nursing Behavior. AB - Parental imprinting is a mammalian-specific form of epigenetic regulation in which one allele of a gene is silenced depending on its parental origin. Parentally imprinted genes have been shown to play a role in growth, metabolism, cancer, and behavior. Although the molecular mechanisms underlying parental imprinting have been largely elucidated, the selective advantage of silencing one allele remains unclear. The mutant phenotype of the imprinted gene, Pw1/Peg3, provides a key example to illustrate the hypothesis on a coadaptation between mother and offspring, in which Pw1/Peg3 is required for a set of essential maternal behaviors, such as nursing, nest building, and postnatal care. We have generated a novel Pw1/Peg3 mutant allele that targets the last exon for the PW1 protein that contains >90% of the coding sequence resulting in a loss of Pw1/Peg3 expression. In contrast to previous reports that have targeted upstream exons, we observe that maternal behavior and lactation are not disrupted upon loss of Pw1/Peg3. Both paternal and homozygous Pw1/Peg3 mutant females nurse and feed their pups properly and no differences are detected in either oxytocin neuron number or oxytocin plasma levels. In addition, suckling capacities are normal in mutant pups. Consistent with previous reports, we observe a reduction of postnatal growth. These results support a general role for Pw1/Peg3 in the regulation of body growth but not maternal care and lactation. PMID- 27187725 TI - Analysis of the components of a cognitive-behavioral intervention administered via conference call for preventing depression among non-professional caregivers: a pilot study. AB - OBJECTIVES: The primary aim was to assess the feasibility/acceptability of a preventive cognitive-behavioral intervention implemented via conference call for caregivers. The secondary aim was to conduct a preliminary assessment of the efficacy of the behavioral activation component alone compared to the complete cognitive-behavioral intervention. METHOD: Sixty-one caregivers (mean age 58.4 years) were randomly assigned to a cognitive-behavioral intervention via conference call (CBC, n = 20), a behavioral activation intervention via conference call (BAC, n = 22) or a control group receiving usual care (CG, n = 19). Both interventions consisted of five 90-minute group sessions implemented weekly. RESULTS: Only 6.6% of caregivers discontinued the study. In the CBC and BAC groups, attendance and satisfaction with the intervention were similarly high among both groups. Homework adherence was also high in both groups. At post treatment, there was a lower incidence of depression in the CBC and BAC groups compared to the CG (0.0% for BAC and CBC vs. 10.5% for CG). The relative risk was 0.0, and number needed to treat was 10 in both groups. Depressive symptoms were significantly reduced in the CBC and BAC groups compared to the CG (d = 2.18 and d = 2.06). CONCLUSION: The results support the feasibility of the intervention. Moreover, the BAC intervention was non-inferior to the CBC intervention for reducing depressive symptoms. PMID- 27187727 TI - FDG PET/CT Imaging of Prostate Carcinosarcoma. AB - We present a case of carcinosarcoma of the prostate. Workup of urinary retention after a previously treated squamous cell carcinoma of the prostate led to a transurethral prostate resection revealing carcinosarcoma of the prostate, which on F-FDG PET/CT demonstrated moderate to high avidity of this atypical prostate cancer, with partial obstruction of the urinary system and lung metastases. While FDG PET is not avid for typical prostatic adenocarcinomas, it should be considered for evaluation of atypical prostate cancers. PMID- 27187728 TI - Cocktail Therapy of 177Lu-PSMA-617 and 177Lu-EDTMP in Patients With mCRPC: A Proof-of-Principle Application. AB - Prostate cancer is the second most common primary tumor affecting men worldwide. Among them, 10-20% develop castration resistant prostate cancer (CRPC). Ga-PSMA PET/CT is an important theranostic agent for the evaluation of CRPC to assess the feasibility of treatment with Lu-PSMA-617 which is a novel therapeutic agent. Interestingly, in certain cases, we have observed non-PSMA-avid lesions despite raised sPSA levels. In this regard, we present a case of cocktail therapy applied using Lu-PSMA-617 and Lu-EDTMP therapy in a 38-year-old male CRPC patient with both soft tissue and extensive skeletal metastases. PMID- 27187726 TI - Simplified Models of Non-Invasive Fractional Flow Reserve Based on CT Images. AB - Invasive fractional flow reserve (FFR) is the gold standard to assess the functional coronary stenosis. The non-invasive assessment of diameter stenosis (DS) using coronary computed tomography angiography (CTA) has high false positive rate in contrast to FFR. Combining CTA with computational fluid dynamics (CFD), recent studies have shown promising predictions of FFRCT for superior assessment of lesion severity over CTA alone. The CFD models tend to be computationally expensive, however, and require several hours for completing analysis. Here, we introduce simplified models to predict noninvasive FFR at substantially less computational time. In this retrospective pilot study, 21 patients received coronary CTA. Subsequently a total of 32 vessels underwent invasive FFR measurement. For each vessel, FFR based on steady-state and analytical models (FFRSS and FFRAM, respectively) were calculated non-invasively based on CTA and compared with FFR. The accuracy, sensitivity, specificity, positive predictive value and negative predictive value were 90.6% (87.5%), 80.0% (80.0%), 95.5% (90.9%), 88.9% (80.0%) and 91.3% (90.9%) respectively for FFRSS (and FFRAM) on a per-vessel basis, and were 75.0%, 50.0%, 86.4%, 62.5% and 79.2% respectively for DS. The area under the receiver operating characteristic curve (AUC) was 0.963, 0.954 and 0.741 for FFRSS, FFRAM and DS respectively, on a per-patient level. The results suggest that the CTA-derived FFRSS performed well in contrast to invasive FFR and they had better diagnostic performance than DS from CTA in the identification of functionally significant lesions. In contrast to FFRCT, FFRSS requires much less computational time. PMID- 27187729 TI - 18F-DOPA PET/CT and MRI Findings in a Patient With Multiple Meningiomas. AB - A 56-year-old man was referred to our Department for a 2-year story of upper limb tremor, severe headache, and episodes of confusion. Brain F-DOPA PET/CT showed multiple areas of tracer uptake in the two hemispheres of the brain. Subsequent MRI displayed demyelinating foci with high contrast enhancement. Histological specimen confirmed the diagnosis of multiple meningiomas. PMID- 27187731 TI - Putative Physiopathological Explanation for the "Sock Sign" in Bone Scans. AB - Four patients were referred to our department to undergo a bone scan for suspected reflex sympathetic dystrophy in the upper limbs. After TC-HMDP injection in the foot, they developed a "sock sign," defined by highly increased uptake in the injected lower limb. The sock sign has been previously described in only 1 case in the literature and attributed to intra-arterial injection. Our images suggest that the sock sign might instead be the consequence of tracer extravasation at the injection site. PMID- 27187730 TI - Assessment of Aggressiveness of Breast Cancer Using Simultaneous 18F-FDG-PET and DCE-MRI: Preliminary Observation. AB - PURPOSE: This study aims to investigate the feasibility of using simultaneous breast MRI and PET to assess the synergy of MR pharmacokinetic and fluorine-18 fluorodeoxyglucose (F-FDG) uptake data to characterize tumor aggressiveness in terms of metastatic burden and Ki67 status. METHODS: Twelve consecutive patients underwent breast and whole-body PET/MRI. During the MR scan, PET events were simultaneously accumulated. MR contrast kinetic model parametric maps were computed using the extended Tofts model, including the volume transfer constant between blood plasma and the interstitial space (K), the transfer constant from the interstitial space to the blood plasma (kep), and the plasmatic volume fraction (Vp). RESULTS: Patients with systemic metastases had a significantly lower kep compared to those with local disease (0.45 vs. 0.99 min, P = 0.011). Metastatic burden correlated positively with K and standardized uptake value (SUV), and negatively with kep. Ki67 positive tumors had a significantly greater K compared to Ki67 negative tumors (0.29 vs. 0.45 min, P = 0.03). A negative correlation was found between metabolic tumor volume and transfer constant (K or Kep). CONCLUSION: These preliminary results suggest that MR pharmacokinetic parameters and FDG-PET may aid in the assessment of tumor aggressiveness and metastatic potential. Future studies are warranted with a larger cohort to further assess the role of pharmacokinetic modeling in simultaneous PET/MRI imaging. PMID- 27187732 TI - FDG PET/CT in Peritoneal Metastasis From Prostate Cancer. AB - Prostate cancer is one of the leading causes of cancer death in men. The prognosis in prostate cancer is greatly worsened by the presence of metastases, which are most commonly found in bone, lung, liver, and brain. The peritoneum is an extremely uncommon metastatic site for prostate cancer, even in autopsy series. We present a case of FDG PET/CT demonstration of peritoneal metastasis from prostate cancer. PMID- 27187733 TI - FDG-PET/CT of Vulvar Adenocarcinoma With Diffuse Metastases. AB - A 52 year-old woman presented to her gynecologist with a 1-year history of a 1.5 cm left labial mass. Punch biopsy of the vulvar lesion revealed primary infiltrating adenocarcinoma. Staging FDG-PET/CT demonstrated multiorgan diffuse metastases. PMID- 27187734 TI - A False-Negative Case of Primary Central Nervous System Lymphoma on 11C Methionine PET and Intense 18F-FDG Uptake. AB - We report a case of a 44-year-old man with neurological symptoms and MRI findings, which were unable to differentiate between glioma and lymphoma. Metabolic characterization by means of PET imaging with F-FDG and C-methionine is proposed to determine the benign or tumor (high- and low-grade) origin of brain lesions. In this case, the MRI lesion corresponded with an inconclusive metabolic pattern of intense F-FDG uptake and no significant C-methionine uptake. Pathological study revealed a false-negative case of C-methionine due to lymphoma. PMID- 27187735 TI - IgG4-Related Kidney Disease in a Patient With History of Breast Cancer: Findings on 18F-FDG PET/CT. AB - A 64-year-old African American woman with history of stage III breast carcinoma, 3 years after complete response to therapy, presents with progressive fatigue, increasing arthralgia, and unintentional weight loss of 15 lb in 3 months. An F FDG PET demonstrated new diffuse FDG avidity of the renal parenchyma, new FDG avid foci in pancreas and lungs, and new FDG-avid lymph nodes above and below the diaphragm. While a retroperitoneal lymph node biopsy was inconclusive, a kidney biopsy resulted in diagnosis of diffuse, severe, IgG4-related tubulointerstitial nephritis. Treatment with corticosteroid led to complete resolution of the symptoms and PET findings. PMID- 27187736 TI - Endometriosis Mimicking an Advanced Malignant Tumor. AB - A 27-year-old woman with swelling left leg, groin pain, and increased serum CA125 level underwent FDG PET/CT to evaluate a pelvic mass revealed by an MRI performed from an outside hospital. A large hypermetabolic solid mass in the left pelvic wall and several lymph nodes with elevated FDG activity were noted, which indicated malignancy. However, histopathological examination demonstrated endometriosis. PMID- 27187737 TI - Bone Morphogenic Protein Type 2 Receptor Mutation-Independent Mechanisms of Disrupted Bone Morphogenetic Protein Signaling in Idiopathic Pulmonary Arterial Hypertension. AB - Altered bone morphogenic protein (BMP) signaling, independent of BMPR2 mutations, can result in idiopathic pulmonary arterial hypertension (IPAH). Glucose dysregulation can regulate multiple processes in IPAH. However, the role of glucose in BMP antagonist expression in IPAH has not been characterized. We hypothesized that glucose uptake regulates BMP signaling through stimulation of BMP antagonist expression in IPAH. Using human plasma, lung tissue, and primary pulmonary arterial smooth muscle cells (PASMCs), we examined the protein expression of BMP2, BMP-regulated Smads, and Smurf-1 in patients with IPAH and control subjects. Gremlin-1 levels were elevated in patients with IPAH compared with control subjects, whereas expression of BMP2 was not different. We demonstrate increased Smad polyubiquitination in IPAH lung tissue and PASMCs that was further enhanced with proteasomal inhibition. Examination of the Smad ubiquitin-ligase, Smurf-1, showed increased protein expression in IPAH lung tissue and localization in the smooth muscle of the pulmonary artery. Glucose dose dependently increased Smurf-1 protein expression in control PASMCs, whereas Smurf-1 in IPAH PASMCs was increased and sustained. Conversely, phospho-Smad1/5/8 levels were reduced in IPAH compared with control PASMCs at physiological glucose concentrations. Interestingly, high glucose concentrations decreased phosphorylation of Smad1/5/8 in control PASMCs. Blocking glucose uptake had opposing effects in IPAH PASMCs, and inhibition of Smurf-1 activity resulted in partial rescue of Smad1/5/8 activation and cell migration rates. Collectively, these data suggest that BMP signaling can be regulated through BMPR2 mutation independent mechanisms. Gremlin-1 (synonym: induced-in-high-glucose-2 protein) and Smurf-1 may function to inhibit BMP signaling as a consequence of the glucose dysregulation described in IPAH. PMID- 27187739 TI - Second-Generation Phenylthiazole Antibiotics with Enhanced Pharmacokinetic Properties. AB - A series of second-generation analogues for 2-(1-(2-(4-butylphenyl)-4 methylthiazol-5-yl)ethylidene)aminoguanidine (1) have been synthesized and tested against methicillin-resistant Staphylococcus aureus (MRSA). The compounds were designed with the objective of improving pharmacokinetic properties. This main aim has been accomplished by replacing the rapidly hydrolyzable Schiff-base moiety of first-generation members with a cyclic, unhydrolyzable pyrimidine ring. The hydrazide-containing analogue 17 was identified as the most potent analogue constructed thus far. The corresponding amine 8 was 8 times less active. Finally, incorporating the nitrogenous side chain within an aromatic system completely abolished the antibacterial character. Replacement of the n-butyl group with cyclic bioisosteres revealed cyclohexenyl analogue 29, which showed significant improvement in in vitro anti-MRSA potency. Increasing or decreasing the ring size deteriorated the antibacterial activity. Compound 17 demonstrated a superior in vitro and in vivo pharmacokinetic profile, providing compelling evidence that this particular analogue is a good drug candidate worthy of further analysis. PMID- 27187738 TI - Reduced Uterine Perfusion Pressure (RUPP) Model of Preeclampsia in Mice. AB - Preeclampsia (PE) is a pregnancy-induced hypertension with proteinuria that typically develops after 20 weeks of gestation. A reduction in uterine blood flow causes placental ischemia and placental release of anti-angiogenic factors such as sFlt-1 followed by PE. Although the reduced uterine perfusion pressure (RUPP) model is widely used in rats, investigating the role of genes on PE using genetically engineered animals has been problematic because it has been difficult to make a useful RUPP model in mice. To establish a RUPP model of PE in mice, we bilaterally ligated ovarian vessels distal to ovarian branches, uterine vessels, or both in ICR-strain mice at 14.5 days post coitum (dpc). Consequently, these mice had elevated BP, increased urinary albumin excretion, severe endotheliosis, and mesangial expansion. They also had an increased incidence of miscarriage and premature delivery. Embryonic weight at 18.5 dpc was significantly lower than that in sham mice. The closer to the ligation site the embryos were, the higher the resorption rate and the lower the embryonic weight. The phenotype was more severe in the order of ligation at the ovarian vessels < uterine vessels < both. Unlike the RUPP models described in the literature, this model did not constrict the abdominal aorta, which allowed BP to be measured with a tail cuff. This novel RUPP model in mice should be useful for investigating the pathogenesis of PE in genetically engineered mice and for evaluating new therapies for PE. PMID- 27187740 TI - Vasopressinergic control of stress-related behavior: studies in Brattleboro rats. AB - Vasopressin, a nonapeptide, signaling both as hormone in the blood and neuromodulator/neurotransmitter in the brain is considered to be causally involved in the pathological changes underlying anxiety and depression. In the present review we summarize experimental data obtained with Brattleboro rats as a model of congenital vasopressin-deficiency to test the hypothesis that central vasopressin signaling contributes to anxiety- and depression-like behavior. Male, female and lactating rats were studied. We focused on the paraventricular nucleus of the hypothalamus (PVN) and the septum, two brain areas in which vasopressin is proposed to control the endocrine and behavioral stress response, respectively. The presented data support the hypothesis that the behavioral changes seen in these rats are brought about by an altered vasopressin signaling at the brain level. Whereas vasopressin synthesized and released within the hypothalamus is primarily involved in endocrine regulation, vasopressin signaling in other brain areas may contribute to anxiety- and depression-like behavioral parameters. Further studies in this context might focus particularly on the interplay between extra-hypothalamic brain areas such as the septum and the medial amygdala. PMID- 27187741 TI - Forest Management Intensity Affects Aquatic Communities in Artificial Tree Holes. AB - Forest management could potentially affect organisms in all forest habitats. However, aquatic communities in water-filled tree-holes may be especially sensitive because of small population sizes, the risk of drought and potential dispersal limitation. We set up artificial tree holes in forest stands subject to different management intensities in two regions in Germany and assessed the influence of local environmental properties (tree-hole opening type, tree diameter, water volume and water temperature) as well as regional drivers (forest management intensity, tree-hole density) on tree-hole insect communities (not considering other organisms such as nematodes or rotifers), detritus content, oxygen and nutrient concentrations. In addition, we compared data from artificial tree holes with data from natural tree holes in the same area to evaluate the methodological approach of using tree-hole analogues. We found that forest management had strong effects on communities in artificial tree holes in both regions and across the season. Abundance and species richness declined, community composition shifted and detritus content declined with increasing forest management intensity. Environmental variables, such as tree-hole density and tree diameter partly explained these changes. However, dispersal limitation, indicated by effects of tree-hole density, generally showed rather weak impacts on communities. Artificial tree holes had higher water temperatures (on average 2 degrees C higher) and oxygen concentrations (on average 25% higher) than natural tree holes. The abundance of organisms was higher but species richness was lower in artificial tree holes. Community composition differed between artificial and natural tree holes. Negative management effects were detectable in both tree-hole systems, despite their abiotic and biotic differences. Our results indicate that forest management has substantial and pervasive effects on tree-hole communities and may alter their structure and functioning. We furthermore conclude that artificial tree-hole analogues represent a useful experimental alternative to test effects of changes in forest management on natural communities. PMID- 27187742 TI - Thymic stromal lymphopoietin in tonsillar follicular dendritic cells correlates with elevated serum immunoglobulin A titer by promoting tonsillar immunoglobulin A class switching in immunoglobulin A nephropathy. AB - Immunoglobulin A (IgA) nephropathy (IgAN) is characterized by high serum IgA levels and IgA deposition in the renal mesangium. Previous studies suggest that elevated serum IgA partly originates from the tonsils. Here, we investigated the mechanisms of IgA production in the tonsils of patients with IgAN. Immunohistochemistry revealed that the number and relative percentage of IgA bearing cells were significantly increased in the tonsils of IgAN patients. Compared with non-IgAN patients, enhanced IgA class switching and overexpression of thymic stromal lymphopoietin (TSLP), TSLP receptor (TSLPR), activation-induced cytidine deaminase (AID), transforming growth factor-beta1 (TGF-beta1), B cell activating factor of the tumor necrosis factor family (BAFF), and a proliferation inducing ligand (APRIL) were detected in follicular dendritic cells (FDCs) of tonsillar germinal centers from IgAN patients. Importantly, TSLP correlated with IgA production in isolated FDC-associated clusters. Serum TSLP levels were increased and correlated with IgA overexpression in the tonsils and serum of IgAN patients. These data indicated that TSLP overexpression in tonsillar FDCs may promote IgA class switching in IgAN patients through the cooperative roles of AID, TGF-beta1, BAFF, and APRIL. Therefore, interactions between TSLP in FDCs and IgA production in tonsils may be an important mechanism contributing to the pathogenesis of IgAN. PMID- 27187744 TI - New modalities of strain-control of ferroelectric thin films. AB - Ferroelectrics, with their spontaneous switchable electric polarization and strong coupling between their electrical, mechanical, thermal, and optical responses, provide functionalities crucial for a diverse range of applications. Over the past decade, there has been significant progress in epitaxial strain engineering of oxide ferroelectric thin films to control and enhance the nature of ferroelectric order, alter ferroelectric susceptibilities, and to create new modes of response which can be harnessed for various applications. This review aims to cover some of the most important discoveries in strain engineering over the past decade and highlight some of the new and emerging approaches for strain control of ferroelectrics. We discuss how these new approaches to strain engineering provide promising routes to control and decouple ferroelectric susceptibilities and create new modes of response not possible in the confines of conventional strain engineering. To conclude, we will provide an overview and prospectus of these new and interesting modalities of strain engineering helping to accelerate their widespread development and implementation in future functional devices. PMID- 27187743 TI - Gut microbiome in chronic kidney disease: challenges and opportunities. AB - More than 100 trillion microbial cells that reside in the human gut heavily influence nutrition, metabolism, and immune function of the host. Gut dysbiosis, seen commonly in patients with chronic kidney disease (CKD), results from qualitative and quantitative changes in host microbiome profile and disruption of gut barrier function. Alterations in gut microbiota and a myriad of host responses have been implicated in progression of CKD, increased cardiovascular risk, uremic toxicity, and inflammation. We present a discussion of dysbiosis, various uremic toxins produced from dysbiotic gut microbiome, and their roles in CKD progression and complications. We also review the gut microbiome in renal transplant, highlighting the role of commensal microbes in alteration of immune responses to transplantation, and conclude with therapeutic interventions that aim to restore intestinal dysbiosis. PMID- 27187746 TI - Early executive control and risk for overweight and obesity in elementary school. AB - An emerging literature suggests that poor executive control (EC) may be associated with clinical weight problems, e.g., body mass index (BMI) for age percentile >=85 in children. However, our understanding of the impact of EC on overweight and obesity in childhood is limited by the lack of longitudinal studies spanning critical developmental periods and assessing EC using comprehensive performance-based batteries. The current study addresses these limitations in a longitudinal examination of 212 children who completed an extensive laboratory-based EC task battery in preschool (age 4 years and 6 months) and were followed through elementary school (Grades 1 through 4) with objective measures of weight status. The logistic regression results indicate that poorer EC in preschool is associated with significantly greater risk for clinical weight problems (either overweight or obese status, as defined by BMI for-age percentile >= 85) in elementary school, controlling for maternal education. EC in preschool was not significantly associated with risk for obese status, specifically (defined by BMI-for-age percentile >= 95), but the trend was in the expected direction. The results suggest that early executive abilities are relevant for children's subsequent health status, with deficits in EC in the critical period of preschool conferring risk for later problems with weight. Based on these findings, early interventions to promote stronger EC may be a promising, yet currently overlooked, component in pediatric obesity prevention efforts. PMID- 27187747 TI - VUV/UV/Chlorine as an Enhanced Advanced Oxidation Process for Organic Pollutant Removal from Water: Assessment with a Novel Mini-Fluidic VUV/UV Photoreaction System (MVPS). AB - Vacuum ultraviolet (VUV) and ultraviolet (UV)/chlorine processes are regarded as two of many advanced oxidation processes (AOPs). Because of the similar cost of VUV/UV and UV lamps, a combination of VUV and UV/chlorine (i.e., VUV/UV/chlorine) may enhance the removal of organic pollutants in water but without any additional power input. In this paper, a mini-fluidic VUV/UV photoreaction system (MVPS) was developed for bench-scale experiments, which could emit both VUV (185 nm) and UV (254 nm) or solely UV beams with a nearly identical UV photon fluence. The photon fluence rates of UV and VUV output by the MVPS were determined to be 8.88 * 10( 4) and 4.93 * 10(-5) einstein m(-2) s(-1), respectively. The VUV/UV/chlorine process exhibited a strong enhancement concerning the degradation of methylene blue (MB, a model organic pollutant) as compared to the total performance of the VUV/UV and UV/chlorine processes, although the photon fluence of the VUV only accounted for 5.6% of that of the UV. An acidic pH favored MB degradation by the VUV/UV/chlorine process. The synergistic mechanism of the VUV/UV/chlorine process was mainly ascribed to the effective use of (*)OH for pollutant removal through formation of longer-lived secondary radicals (e.g., (*)OCl). This study demonstrates that the new VUV/UV/chlorine process, as an enhanced AOP, can be applied as a highly effective and energy-saving technology for small-scale water and wastewater treatment. PMID- 27187745 TI - Ferulic Acid Administered at Various Time Points Protects against Cerebral Infarction by Activating p38 MAPK/p90RSK/CREB/Bcl-2 Anti-Apoptotic Signaling in the Subacute Phase of Cerebral Ischemia-Reperfusion Injury in Rats. AB - OBJECTIVES: This study aimed to evaluate the effects of ferulic acid (FA) administered at various time points before or after 30 min of middle cerebral artery occlusion (MCAo) followed by 7 d of reperfusion and to examine the involvement of mitogen-activated protein kinase (MAPK) signaling pathways in the cortical penumbra. METHODS: FA was intravenously administered to rats at a dose of 100 mg/kg 24 h before ischemia (B-FA), 2 h before ischemia (P-FA), immediately after ischemic insult (I-FA), 2 h after reperfusion (R-FA), or 24 h after reperfusion (D-FA). RESULTS: Our study results indicated that P-FA, I-FA, and R FA effectively reduced cerebral infarct areas and neurological deficits. P-FA, I FA, and R-FA significantly downregulated glial fibrillary acidic protein (GFAP), mitochondrial Bax, cytochrome c, and cleaved caspase-3 expression, and effectively restored the phospho-p38 MAPK (p-p38 MAPK)/p38 MAPK ratio, phospho-90 kDa ribosomal S6 kinase (p-p90RSK) expression, phospho-Bad (p-Bad) expression, the phospho-cAMP response element-binding protein (p-CREB)/CREB ratio, the cytosolic and mitochondrial Bcl-2/Bax ratios, and the cytosolic Bcl-xL/Bax ratio in the cortical penumbra 7 d after reperfusion. SB203580, a specific inhibitor of p38 MAPK, administered 30 min prior to ischemia abrogated the downregulating effects of I-FA on cerebral infarction, and mitochondrial Bax and cleaved caspase 3 expression, and the upregulating effects of I-FA on the p-p38 MAPK/p38 MAPK ratio, p-p90RSK expression, p-Bad expression, and the p-CREB/CREB, and cytosolic and mitochondrial Bcl-2/Bax ratios. CONCLUSIONS: Our study results thus indicate that P-FA, I-FA, and R-FA effectively suppress reactive astrocytosis and exert neuroprotective effects against cerebral infarction by activating p38 MAPK signaling. The regulating effects of P-FA, I-FA, and R-FA on Bax-induced apoptosis result from activation of the p38 MAPK/p90RSK/CREB/Bcl-2 signaling pathway, and eventually contribute to inhibition of the cytochrome c-mediated caspase-3-dependent apoptotic pathway in the cortical penumbra 7 d after reperfusion. PMID- 27187748 TI - Concentrations and spatial patterns of organic contaminants in tree swallow (Tachycineta bicolor) eggs at United States and binational Great Lakes Areas of Concern, 2010-2015. AB - Tree swallows, Tachycineta bicolor, were sampled across the Great Lakes basin in 2010 through 2015 to provide a system-wide assessment of current exposure to organic contaminants. The results provide information identified as critical by regulators to assess the "bird or animal deformity or reproductive problems" beneficial use impairment. Eggs were collected from 69 sites across all 5 Great Lakes, including 27 Areas of Concern (AOCs), some with multiple sites, and 10 sites not listed as an AOC. Concentrations of organic contaminants in eggs were quantified and compared with background and reproductive effect thresholds. Approximately 30% of AOCs had geometric mean concentrations of total polychlorinated biphenyls (PCBs) at or below average background exposure (0.34 MUg/g wet wt). Exposure to polybrominated diphenyl ethers (PBDEs) was minimal, and only 3 of 27 AOCs and 1 non-AOC had geometric mean concentrations that exceeded background for tree swallows (96 ng/g wet wt). Concentrations of both PCBs and PBDEs were 10 to 20 times below the lower limit associated with impaired hatching success. In contrast, geometric mean concentrations of polychlorinated dibenzo-p-dioxin and furan (PCDD-F) toxic equivalents (TEQs) at the Saginaw River and Bay AOC and Midland, Michigan, USA (a non-AOC site), exceeded the lower limit for hatching effects (181 pg/g PCDD-F TEQs). The rest of the sites had geometric mean concentrations of PCDD-F TEQs below background levels (87 pg/g PCDD-F TEQs). Other organic contaminants, including p,p'-dichlorodiphenyldichloroethylene, mirex, heptachlor, and chlordane, were at or below background or adverse effect concentrations. Environ Toxicol Chem 2016;35:3071-3092. Published 2016 Wiley Periodicals Inc on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America. PMID- 27187749 TI - Systemic inflammation and liver damage in HIV/hepatitis C virus coinfection. AB - OBJECTIVES: Chronic hepatitis C virus (HCV) and HIV viral infections are characterized by systemic inflammation. Yet the relative levels, drivers and correlates of inflammation in these settings are not well defined. METHODS: Seventy-nine HIV-infected patients who had been receiving antiretroviral therapy (ART) for more than 2 years and who had suppressed plasma HIV levels (< 50 HIV-1 RNA copies/mL) were included in the study. Two patient groups, HCV-positive/HIV positive and HCV-negative/HIV-positive, and a control group comprised of healthy volunteers (n = 20) were examined. Markers of systemic inflammation [interleukin (IL)-6, interferon gamma-induced protein (IP)-10, soluble tumour necrosis factor receptor-I (sTNF-RI) and sTNF-RII], monocyte/macrophage activation [soluble CD163 (sCD163), soluble CD14 and neopterin], intestinal epithelial barrier loss [intestinal fatty acid binding protein (I-FABP) and lipopolysaccharide (LPS)] and coagulation (d-dimers) were analysed. CD4 naive T cells and CD4 recent thymic emigrants (RTEs) were enumerated. RESULTS: Plasma levels of IP-10, neopterin and sCD163 were higher in HCV/HIV coinfection than in HIV monoinfection and were positively correlated with indices of hepatic damage [aspartate aminotransferase (AST), alanine aminotransferase (ALT) and the AST to platelet ratio index (APRI)]. Levels of I-FABP were comparably increased in HIV monoinfection and HIV/HCV coinfection but LPS concentrations were highest in HCV/HIV coinfection, suggesting impaired hepatic clearance of LPS. Plasma HCV levels were not related to any inflammatory indices except sCD163. In coinfected subjects, a previously recognized relationship of CD4 naive T-cell and RTE counts to hepatocellular injury was defined more mechanistically by an inverse relationship to sCD163. CONCLUSIONS: Hepatocellular injury in HCV/HIV coinfection is linked to elevated levels of certain inflammatory cytokines and an apparent failure to clear systemically translocated microbial products. A related decrease in CD4 naive T cells and RTEs also merits further exploration. PMID- 27187750 TI - Tuning the Hydrophilicity and Hydrophobicity of the Respective Cation and Anion: Reversible Phase Transfer of Ionic Liquids. AB - The separation and recycling of catalyst and cocatalyst from the products and solvents are of critical importance. In this work, a class of functionalized ionic liquids (ILs) were designed and synthesized, and by tuning the hydrophilicity and hydrophobicity of cation and anion, respectively, these ILs could reversibly transfer between water and organics triggered upon undergoing a temperature change. From a combination of multiple spectroscopic techniques, it was shown that the driving force behind the transfer was originated from a change in conformation of the PEG chain of the IL upon temperature variation. By utilizing the novel property of this class of ILs, a highly efficient and controllable CuI-catalyzed cycloaddition reaction was achieved wherein the IL was used to entrain, activate, and recycle the catalyst, as well as to control the reaction. PMID- 27187751 TI - Frequent life-threatening laryngeal attacks in two Croatian families with hereditary angioedema due to C1 inhibitor deficiency harbouring a novel frameshift mutation in SERPING1. AB - OBJECTIVE: Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare autosomal dominant disease caused by mutations in the SERPING1 gene. It can affect many regions in the body, but potentially life-threatening laryngeal oedemas are of concern. METHODS: Twenty-three subjects from two families were recruited for clinical data evaluation and molecular analysis at General Hospital Sibenik, Croatia. RESULTS: Decreased levels of C1 inhibitor were detected in 12 adult patients and three young asymptomatic persons. The same novel deletion of two nucleotides on exon 3 (c.74_75delAT) was identified in all of them. A history of laryngeal oedema was present in 10 patients (83%), and all patients reported laryngeal attacks at least once a year. The delay in diagnosis decreased noticeably from the first to the last generation. CONCLUSIONS: We identified a novel causative mutation in SERPING1 in several affected members of two apparently unrelated families with a high frequency of laryngeal oedema. Molecular analysis of large C1-INH-HAE families will provide new insights on the genotype-phenotype relationship. Key messages Hereditary angioedema due to C1 inhibitor deficiency is a rare autosomal dominant disease caused by mutations in the SERPING1 gene, and laryngeal oedema is of concern because it can cause death by asphyxiation. A novel causative mutation in SERPING1, a deletion of two nucleotides on exon 3 (c.74_75delAT), was identified in several affected members of two apparently unrelated families with a high frequency of laryngeal oedema. Molecular analysis of large C1-INH-HAE families will provide new insights on the genotype-phenotype relationship because it appears that the mutation type may affect disease severity. PMID- 27187752 TI - Avian influenza virus in pregnancy. AB - The unprecedented epizootic of avian influenza viruses, such as H5N1, H5N6, H7N1 and H10N8, has continued to cause disease in humans in recent years. In 2013, another novel influenza A (H7N9) virus emerged in China, and 30% of those patients died. Pregnant women are particularly susceptible to avian influenza and are more likely to develop severe complications and to die, especially when infection occurs in the middle and late trimesters. Viremia is believed to occur infrequently, and thus vertical transmission induced by avian influenza appears to be rare. However, avian influenza increases the risk of adverse pregnancy outcomes, including spontaneous abortion, preterm birth and fatal distress. This review summarises 39 cases of pregnant women and their fetuses from different countries dating back to 1997, including 11, 15 and 13 infections with H7N9, H5N1 and the 2009 pandemic influenza (H1N1), respectively. We analysed the epidemic features, following the geographical, population and pregnancy trimester distributions; underlying diseases; exposure history; medical timelines; human-to human transmission; pathogenicity and vertical transmission; antivirus treatments; maternal severity and mortality and pregnancy outcome. The common experiences reported in different countries and areas suggest that early identification and treatment are imperative. In the future, vigilant virologic and epidemiologic surveillance systems should be developed to monitor avian influenza viruses during pregnancy. Furthermore, extensive study on the immune mechanisms should be conducted, as this will guide safe, rational immunomodulatory treatment among this high-risk population. Most importantly, we should develop a universal avian influenza virus vaccine to prevent outbreaks of the different subtypes. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27187755 TI - The Cost-effectiveness of Varicella Zoster Virus Vaccination Considering Late Onset Asthma. AB - BACKGROUND: Recent studies reported that infection by varicella zoster virus (VZV) may lead to delayed onset of asthma in children/adolescents. This information will likely alter the cost-effectiveness of the US. VZV vaccination program. We created a decision analysis model to estimate the costs and health related effects of VZV 2-dose vaccination, assuming VZV infection delays asthma onset. METHODS: The Markov model considered a birth cohort of 3,957,577 individuals entering the population from a societal perspective. We predicted the number of asthma/VZV cases, asthma-/VZV-related mortality and costs associated with asthma/VZV. Comparison arms included (1) VZV vaccination program without delayed asthma onset, (2) VZV vaccination program with delayed asthma onset and (3) no VZV vaccination program with delayed asthma onset. We considered delayed onset ranging from 3 to 12 years. RESULTS: The vaccination program proved cost effective without an assumed delay in asthma onset. When the vaccination and no vaccination arms were compared assuming delayed asthma onset, vaccination remained less costly despite increased savings related to asthma without vaccination. With delayed asthma onset of 9 years post VZV infection, cost savings due to vaccination were $914.09 million, with 9984 cases of asthma averted and 9 greater overall deaths with vaccination. CONCLUSION: VZV vaccination program was less costly than the "no-vaccination" scenario, despite delayed onset of asthma post VZV infection. However, vaccination resulted in increased asthma morbidity and mortality. This adds to current evidence that VZV vaccination is cost-effective, and may alter asthma-related health-care outcomes. VZV's effect on asthma symptoms still needs further evaluation before firm conclusions can be reached. PMID- 27187754 TI - Cryptococcal Meningitis Presenting as a Complication in HIV-infected Children: A Case Series From Sub-Saharan Africa. AB - Cryptococcal meningitis is a leading infectious disease worldwide as a result of the high burden of HIV and AIDS, although its cumulative incidence is very low in children compared with that in adults. Very few studies involving the disease in children have been reported including sub-Saharan Africa, with the highest prevalence of HIV-infected children in the world. We summarize 5 cases of children diagnosed with cryptococcal meningitis at a tertiary hospital in Harare, Zimbabwe, between October 1, 2013, and September 30, 2014. PMID- 27187753 TI - Rilpivirine Pharmacokinetics Without and With Darunavir/Ritonavir Once Daily in Adolescents and Young Adults. AB - BACKGROUND: Rilpivirine (RPV), a recently developed, once daily human immunodeficiency virus non-nucleoside reverse transcriptase inhibitor, is not currently approved for pediatric patients, but is sometimes prescribed for adolescents with multiple treatment failures, for regimen simplification or to minimize toxicity. Darunavir/ritonavir (DRV/r) administered once daily is also increasingly used in adolescents and may alter RPV pharmacokinetics (PK). We evaluated the PK interactions between RPV and DRV/r once daily in adolescents and young adults. METHODS: Human immunodeficiency virus-infected subjects 12 to <24 years old receiving a stable background therapy including RPV 25 mg once daily without or combined with DRV/r 800/100 mg once daily were enrolled. Intensive 24 hour blood sampling was performed, and PK indices were determined using noncompartmental analysis. Protocol-defined target drug exposure ranges based on adult data were used to assess the adequacy of each regimen. RESULTS: Fifteen subjects receiving RPV without and 14 subjects with DRV/r were enrolled. When dosed without DRV/r, the RPV geometric mean (90% confidence interval) for RPV AUC0-24, Cmax and C24 h were 2.38 MUg h/mL (1.92-2.94), 0.14 MUg/mL (0.12-0.18) and 0.07 MUg/mL (0.03-0.10), respectively, similar to adult values. RPV concentrations were significantly increased with concomitant DRV/r use: RPV AUC24, Cmax and C24 h were 6.74 MUg h/mL (4.89-9.28), 0.39 MUg/mL (0.27-0.57) and 0.23 MUg/mL (0.17-0.32), respectively, well above the target ranges based on adult data. DRV/r PK was not affected by coadministration of RPV. CONCLUSIONS: RPV PK in this adolescent population was similar to adults when dosed without DRV/r. DRV/r coadministration increased RPV exposure 2- to 3-fold, indicating that drug-related side effects should be closely monitored. PMID- 27187756 TI - Biomarkers in Cerebrospinal Fluid of Children With Tick-borne Encephalitis: Association With Long-term Outcome. AB - BACKGROUND: Tick-borne encephalitis (TBE) is a major cause of meningoencephalitis in children in endemic areas, and long-term residual problems are not uncommon. Currently, no predictive markers in the acute phase are available that identify children at risk of incomplete recovery. We measured cytokines, chemokines and markers of neuronal damage in cerebrospinal fluid (CSF) in children with TBE and central nervous system (CNS) involvement. METHODS: CSF from 37 children with TBE with CNS involvement was analyzed. Concentrations of 16 cytokines, chemokines and 5 markers of neuronal damage were assessed in CSF, using a multiplex assay, and correlated with clinical findings in the acute phase (n = 37), and with long-term outcome (n=22). RESULTS: Significantly higher levels of CSF interferon (IFN) gamma, interleukin (IL)-4, IL-6 and IL-8 were detected in the acute phase from children who later developed sequelae. Although most of the studied markers of neuronal damage displayed no significant differences between children with sequelae and those with good outcome, neuron-specific enolase correlated inversely. The grade of CSF pleocytosis correlated positively with the levels of IFN-gamma, IL-4 and IL-6; however, pleocytosis alone did not predict sequelae. Increasing age correlated positively with IL-4, IL-6 and IL-8 values. CONCLUSIONS: The mechanism underlying the CNS pathology causing sequelae in TBE appears related to the grade of inflammation in CNS, rather than to direct neuronal destruction. High concentration of IFN-gamma, IL-4, IL-6 and IL-8 in CSF might indicate a risk for incomplete recovery in childhood TBE. PMID- 27187757 TI - Pediatric Access and Continuity of HIV Care Before the Start of Antiretroviral Therapy in Sub-Saharan Africa. AB - BACKGROUND: The number of HIV-infected children starting antiretroviral treatment (ART) has increased in resource-limited settings during the past decades. However, there are still few published data on the characteristics of pediatric patients at program enrolment and on the dynamics of dropping out before the start of ART. METHODS: We performed a retrospective cohort study among HIV infected pediatric patients (age, 5-14 years) not yet started on ART enrolled in 4 HIV sub-Saharan African programs. Descriptive and risk factors for mortality and lost to follow-up (LFU) were investigated using adjusted parametric or Cox proportional hazard models. RESULTS: A total of 2244 patients (52.8% girls) were enrolled in HIV care, a median of 2 days [interquartile range (IQR), 0-8 days] after HIV diagnosis. Baseline median CD4 cell count was 409 cells/MUL (IQR, 203 478 cells/MUL); 43% were in clinical stage 3 or 4, 71% required ART and 76.2% of these patients initiated therapy. Of those eligible not started on ART, 14% died and 59% were LFU. Median pre-ART follow-up was 4.4 months (IQR, 1.3-20 months) and was shorter for eligible patients. Mortality rates were 6.2 of 100 person years [95% confidence interval (CI), 4.6-8.3] in the 0- to 6-month period and 1.3 of 100 person-years (95% CI, 0.9-2.0) in the 6- to 60-month period. LFU rates were 37.4 of 100 (95% CI, 33.0-42.4) and 8.3 of 100 person-years (95% CI, 7.1 9.8), respectively. Advanced HIV disease at presentation (low body mass index, stage 3 or 4, low CD4 count or tuberculosis diagnosis) was associated with increased mortality and LFU. CONCLUSIONS: Late presentation and delays in initiating ART among eligible children were responsible for the large incidence of patient losses during pre-ART follow-up in sub-Saharan Africa. PMID- 27187758 TI - Structural Analogues of Selfotel. AB - A small library of phosphonopiperidylcarboxylic acids, analogues of NMDA antagonist selfotel (CGS 19755), was synthesized. First, the series of aromatic esters was obtained via a palladium-catalyzed cross-coupling reaction (Hirao coupling) of dialkyl phosphites with bromopyridinecarboxylates, followed by their hydrolysis. Then, hydrogenation of the resulting phosphonopyridylcarboxylic acids over PtO2 yielded the desired phosphonopiperidylcarboxylic acids. NMR studies indicated that the hydrogenation reaction proceeds predominantly by cis addition. Several compounds were obtained as monocrystal structures. Preliminary biological studies performed on cultures of neurons suggest that the obtained compounds possess promising activity toward NMDA receptors. PMID- 27187759 TI - A diagnostic algorithm for tuberculous pleurisy using the ELISPOT assay on peripheral blood and pleural effusion. AB - BACKGROUND: Diagnosis of tuberculous (TB) pleurisy remains challenging due to the paucibacillary nature of the disease. We prospectively assessed the diagnostic usefulness of the T-cell based ELISPOT assay, and created a clinical algorithm for differentiating TB pleurisy from other diagnoses. METHODS: All adult patients with suspicion for TB pleurisy were enrolled in a tertiary hospital in Seoul, South Korea, over a 7-year period. ELISPOT assays were performed using mononuclear cells from peripheral blood and pleural effusion. RESULTS: Seventy seven patients with suspected TB pleurisy were enrolled. Of these, 33 (43%) patients, comprising 27 confirmed and 6 probable TB pleurisy, were classified as TB pleurisy, and 36 (47%) were classified as not TB. The remaining 8 with possible TB pleurisy were excluded from the final analysis. The sensitivities and specificities, respectively, of the diagnostic methods were as follows: pleural fluid adenosine deaminase (ADA) level 32 U/L, 81% and 79%; peripheral blood mononuclear cells (PBMC) ELISPOT assay, 82% and 73%; pleural effusion-mononuclear cells (PE-MC) ELISPOT assay, 58% and 87%. When the diagnostic algorithm was applied, PBMC ELISPOT >=6 spots or ADA >=32 U/L' as a rule-out test safely excluded 46% (12/26) of the not TB patients, and 'PE-MC >=6 spots' as a rule-in test accurately classified 23% (7/31) of the patients with TB pleurisy. CONCLUSIONS: A diagnostic algorithm combining ELISPOT assays and ADA levels in pleural fluid appears to be a promising and non-invasive approach for patients with suspected TB pleurisy. PMID- 27187761 TI - The effect of losartan on progressive aortic dilatation in patients with Marfan's syndrome: a meta-analysis of prospective randomized clinical trials. AB - OBJECTIVE: To assess the effect of losartan therapy on progressive aortic dilatation and on clinical outcome in patients with Marfan's syndrome (MFS). METHODS: The meta-analysis was instituted, which included studies identified by a systematic review of MEDLINE of peer-reviewed publications. Echocardiogram or MRI measurements of the aortic root dimension and outcome measures of death, cardiovascular surgery and aortic dissection or rupture were compared between patients who were treated and untreated with losartan therapy. RESULTS: Six randomized trials with 1398 subjects met all the inclusion criteria and were included in the meta-analysis. Compared with non-losartan treatment, losartan therapy significantly decreased the rate of aortic dilatation (SMD=-0.13 with 95% CI -0.25 to 0.00, p=0.04). The clinical outcome beneficial was not observed in the losartan treatment group when compared with no losartan treatment group (odds ratio=1.04 with 95% CI of 0.57-1.87). CONCLUSION: Given the current results of the meta-analysis and together with the lack of associated side effects, it would be reasonable to use losartan in MFS patients with aortic root dilatation. However, no clinical outcome benefits were observed in the losartan treatment group when compared with no losartan treatment group. PMID- 27187760 TI - Characterization of RNA-binding properties of the archaeal Hfq-like protein from Methanococcus jannaschii. AB - The Sm and Sm-like proteins are widely distributed among bacteria, archaea and eukarya. They participate in many processes related to RNA-processing and regulation of gene expression. While the function of the bacterial Lsm protein Hfq and eukaryotic Sm/Lsm proteins is rather well studied, the role of Lsm proteins in Archaea is investigated poorly. In this work, the RNA-binding ability of an archaeal Hfq-like protein from Methanococcus jannaschii has been studied by X-ray crystallography, anisotropy fluorescence and surface plasmon resonance. It has been found that MjaHfq preserves the proximal RNA-binding site that usually recognizes uridine-rich sequences. Distal adenine-binding and lateral RNA-binding sites show considerable structural changes as compared to bacterial Hfq. MjaHfq did not bind mononucleotides at these sites and would not recognize single stranded RNA as its bacterial homologues. Nevertheless, MjaHfq possesses affinity to poly(A) RNA that seems to bind at the unstructured positive-charged N-terminal tail of the protein. PMID- 27187762 TI - Estimates of premorbid ability in a neurodegenerative disease clinic population: comparing the Test of Premorbid Functioning and the Wide Range Achievement Test, 4th Edition. AB - OBJECTIVE: Two frequently used measures to assess premorbid intellectual ability include the Wide Range Achievement Test, 4th Edition Reading Subtest (WRAT-4 READ) and the Test of Premorbid Functioning (TOPF). The present study compared estimates obtained from these measures in a neurodegenerative disease population. METHOD: Records from 85 referrals seen for neuropsychological evaluation in a neurodegenerative disorders clinic were reviewed. Evaluations included TOPF, WRAT 4 READ, and measures of memory, reasoning, language, and executive functioning. Pairwise correlations and concordance correlation coefficients (CCC) were calculated between raw scores and predicted intelligence estimates. Discrepancy scores were calculated between estimates and data were divided into three groups based on size of standardized discrepancy score: Equal, WRAT-4 READ > TOPF, and TOPF > WRAT-4 READ. analysis of variances compared groups on demographic characteristics and cognitive performance. RESULTS: Despite strong Pearson correlation, CCC between predicted IQ estimates showed poor agreement between measures, with evidence of both fixed and proportional bias. Discrepancies ranged from -24.0 to 22.0 (M = 1.78, SD = 6.65), with TOPF generating higher estimates on average. Individuals performing better on WRAT-4 READ were significantly older (M age = 76.26, SD = 7.53) than those performing similarly on both measures and those performing better on TOPF (F (2, 82) = 7.31, p < .001). All other comparisons between groups on demographic variables and cognitive measures were non-significant. CONCLUSIONS: Estimates of premorbid intelligence obtained from the TOPF and WRAT-4 READ have a strong linear relationship, but systematically generate inconsistent estimates in a neurodegenerative disease clinical sample and should not be used interchangeably. PMID- 27187763 TI - Integrated modeling and design for realizing a two-wheeled wheelchair for disabled. AB - Two-wheeled wheelchairs are considered highly nonlinear and complex systems. The systems mimic a double-inverted pendulum scenario and will provide better maneuverability in confined spaces and also to reach higher level of height for pick and place tasks. The challenge resides in modeling and control of the two wheeled wheelchair to perform comparably to a normal four-wheeled wheelchair. Most common modeling techniques have been accomplished by researchers utilizing the basic Newton's Laws of motion and some have used 3D tools to model the system where the models are much more theoretical and quite far from the practical implementation. This article is aimed at closing the gap between the conventional mathematical modeling approaches where the integrated 3D modeling approach with validation on the actual hardware implementation was conducted. To achieve this, both nonlinear and a linearized model in terms of state space model were obtained from the mathematical model of the system for analysis and, thereafter, a 3D virtual prototype of the wheelchair was developed, simulated, and analyzed. This has increased the confidence level for the proposed platform and facilitated the actual hardware implementation of the two-wheeled wheelchair. Results show that the prototype developed and tested has successfully worked within the specific requirements established. PMID- 27187764 TI - Validation and determination of taselisib, a beta-sparing phosphoinositide 3 kinase (PI3K) inhibitor, in human plasma by LC-MS/MS. AB - A liquid chromatographic-tandem mass spectrometry (LC-MS/MS) method for the determination of taselisib (GDC-0032, RO5537381) concentrations in human plasma has been developed and validated to support bioanalysis of clinical samples. Solid phase extraction (SPE) was used to extract plasma samples (50MUL) and the resulting samples were analyzed using reversed phase chromatography and mass spectrometry coupled with an atmospheric pressure chemical ionization interface. The mass analysis of taselisib was performed using multiple reaction monitoring transitions in positive ionization mode. The method was validated over the calibration curve range 0.400-400ng/mL using linear regression and 1/x(2) weighting. The within-run relative standard deviation (%RSD) ranged from 1.3 to 5.6%, while the between-run %RSD varied from 2.0 to 4.5% for LLOQ, low, medium, medium high and high QCs. The accuracy ranged from 94.7 to 100.3% of nominal for within-run and 96.0-99.0% of nominal for between-run for the same QCs. Extraction recovery of taselisib was between 83.8% and 92.9%. Stability of taselisib was established in human plasma for 977days at -20 degrees C and -70 degrees C and established in sample extracts for 96h when stored at 2 - 8 degrees C. Stable labeled internal standard was used to minimize matrix effects. Mean single dose pharmacokinetic parameters determined using this method for a phase I/II clinical trial were: Cmax=35.2ng/mL, AUC0-inf=1570ngh/mL, and T1/2=39.3h. PMID- 27187766 TI - Role of Distance in Singlet Oxygen Applications: A Model System. AB - Herein, we present a model system that allows the investigation of a directed intramolecular singlet oxygen ((1)O2) transfer. Furthermore, we show the influence of singlet oxygen lifetime and diffusion coefficient (D) on the preference of the intramolecular reaction over the intermolecular one in competition experiments. Finally, we demonstrate the distance dependence in quenching experiments, which enables us to draw conclusions about the role of singlet oxygen and (1)O2 carriers in photodynamic therapy. PMID- 27187765 TI - Bisphenol A is associated with insulin resistance and modulates adiponectin and resistin gene expression in obese children. AB - BACKGROUND: Bisphenol A (BPA) exposure has been associated with increased incidence of diabetes and obesity in adults. OBJECTIVES: To evaluate whether an association between BPA urinary levels and insulin resistance as well as adiponectin and resistin production and serum concentrations may occur in obese children. METHODS: Clinical and biochemical features of 141 obese children were collected. Serum resistin and adiponectin were evaluated. Insulin resistance and urinary BPA levels were assessed. Moreover, the effect of BPA on adiponectin and resistin gene expression in adipocytes from eight normal weight prepubertal children was investigated by quantitative real-time RT-PCR (qPCR). RESULTS: Direct association between BPA and homeostasis model assessment (r = 0.23; p: 0.0069) and a strong inverse association between BPA and adiponectin have been found (r = -0.48; p < 0.0001). In adipocytes, resistin expression was detected only after BPA treatment, while adiponectin expression resulted down-regulated after BPA exposure (p < 0.05 at both 10 and 100 nM BPA concentrations). CONCLUSIONS: We suggest the involvement of BPA in the development of insulin resistance in childhood obesity highlighting that urinary BPA levels are directly associated with insulin resistance regardless of BMI. This association may be explained, at least partly, by the findings that BPA affects resistin and adiponectin production in adipose tissue cultures. PMID- 27187767 TI - Dinucleating Ligand Platforms Supporting Indium and Zinc Catalysts for Cyclic Ester Polymerization. AB - The synthesis of the first alkoxide-bridged indium complex supported by a chiral dinucleating ligand platform (1), along with its zinc analogue (2), is reported. Both complexes are synthesized in a one-pot reaction starting from a chiral dinucleating bis(diamino)phenolate ligand platform, sodium ethoxide, and respective metal salts. The dinucleating indium analogue (7) based on an achiral ligand backbone is also reported. Indium complexes bearing either the chiral or achiral ligand catalyze the ring-opening polymerization of racemic lactide (rac LA) to afford highly heterotactic poly(lactic acid) (PLA; Pr > 0.85). The indium complex bearing an achiral ligand affords essentially atactic PLA from meso-LA. The role of the dinucleating ligand structure in catalyst synthesis and polymerization activity is discussed. PMID- 27187769 TI - Inelastic Scattering of Identical Molecules within Framework of the Mixed Quantum/Classical Theory: Application to Rotational Excitations in H2 + H2. AB - Theoretical foundation is laid out for description of permutation symmetry in the inelastic scattering processes that involve collisions of two identical molecules, within the framework of the mixed quantum/classical theory (MQCT). In this approach, the rotational (and vibrational) states of two molecules are treated quantum-mechanically, whereas their translational motion (responsible for scattering) is treated classically. This theory is applied to H2 + H2 system, and the state-to-state transition cross sections are compared versus those obtained from the full-quantum calculations and experimental results from the literature. Good agreement is found in all cases. It is also found that results of MQCT, where the Coriolis coupling is included classically, are somewhat closer to exact full-quantum results than results of the other approximate quantum methods, where those coupling terms are neglected. These new developments allow applications of MQCT to a broad variety of molecular systems and processes. PMID- 27187768 TI - Is Transcatheter Aortic Valve Implantation of Living Tissue-Engineered Valves Feasible? An In Vitro Evaluation Utilizing a Decellularized and Reseeded Biohybrid Valve. AB - Transcatheter aortic valve implantation (TAVI) is a fast-growing, exciting field of invasive therapy. During the last years many innovations significantly improved this technique. However, the prostheses are still associated with drawbacks. The aim of this study was to create cell-seeded biohybrid aortic valves (BAVs) as an ideal implant by combination of assets of biological and artificial materials. Furthermore, the influence of TAVI procedure on tissue engineered BAV was investigated. BAV (n=6) were designed with decellularized homograft cusps and polyurethane walls. They were seeded with fibroblasts and endothelial cells isolated from saphenous veins. Consecutively, BAV were conditioned under low pulsatile flow (500 mL/min) for 5 days in a specialized bioreactor. After conditioning, TAVI-simulation was performed. The procedure was concluded with re-perfusion of the BAV for 2 days at an increased pulsatile flow (1100 mL/min). Functionality was assessed by video-documentation. Samples were taken after each processing step and evaluated by scanning electron microscopy (SEM), immunohistochemical staining (IHC), and Live/Dead-assays. The designed BAV were fully functioning and displayed physiologic behavior. After cell seeding, static cultivation and first conditioning, confluent cell layers were observed in SEM. Additionally, IHC indicated the presence of endothelial cells and fibroblasts. A significant construction of extracellular matrix was detected after the conditioning phase. However, a large number of lethal cells were observed after crimping by Live/Dead staining. Analysis revealed that the cells while still being present directly after crimping were removed in subsequent perfusion. Extensive regions of damaged cell-layers were detected by SEM-analysis substantiating these findings. Furthermore, increased ICAM expression was detected after re-perfusion as manifestation of inflammatory reaction. The approach to generate biohybrid valves is promising. However, damages inflicted during the crimping process seem not to be immediately detectable. Due to severe impacts on seeded cells, the strategy of living TE valves for TAVI should be reconsidered. PMID- 27187770 TI - Therapist Adherence to Good Psychiatric Practice in a Short-Term Treatment for Borderline Personality Disorder. AB - Therapist adherence describes the quality of interventions according to the imperatives of a treatment model. We examined the relationship between therapist adherence and symptom change in the context of a short-term treatment with respect good psychiatric management (GPM) principles. Based on a parent trial, borderline personality disorder patients (N = 40) benefited from a 10-session intervention. Adherence to GPM was assessed using a GPM Adherence Scale (GPMAS). The psychometric properties of the GPMAS were excellent, and the adherence to GPM explained 16% of the general symptom improvement (t(1) = 2.38, beta = 0.40, p = 0.02) and 23% of the borderline symptom improvement (t(1) = 2.46, beta = 0.48, p = 0.02). Because GPM adherence predicts the outcome after only 10 sessions, GPMAS is a valuable measure early on in psychiatric practice as part of an initial step to longer-term treatment, to quickly detect problems and correct them. PMID- 27187772 TI - Reply: Interplay Between Physical Activity and Sleep in Fatigue Modulation of Cancer Patients. PMID- 27187771 TI - Prevalence and Recognition of Depressive Disorder in Three Medical Outpatient Departments of General Hospitals in Beijing, China. AB - This purpose of this study was to explore the prevalence and recognition of depressive disorders in cardiology, gastroenterology, and neurology outpatient departments of general hospitals. Patients screened with a Hospital Anxiety and Depression Scale score of 8 or higher were interviewed by psychiatrists using Mini-International Neuropsychiatric Interview (MINI). Prevalence of depressive disorders within the cohort was determined, sociodemographic data were analyzed for correlations to a depression diagnosis, and comparisons between the surveys and the clinical diagnosis were done to assess recognition of depressive disorders by physicians. Of the patients screened for this study (1552 cases), 12.8% were diagnosed with depressive disorders by MINI, with major depressive disorder, depression due to general medical conditions, and dysthymia having prevalence values of 10.8%, 1.4%, and 0.6%, respectively. As compared with MINI, physicians only recognized 27.6% of any of the depressive disorders. Among the complaints examined, both mood problems and sleeping problems predicted the probability of recognition. PMID- 27187773 TI - Implementation of World Health Organization Integrated Management of Childhood Illnesses (IMCI) Guidelines for the Assessment of Pneumonia in the Under 5s in Rural Malawi. AB - The Cooking and Pneumonia Study (CAPS) is a pragmatic cluster-level randomized controlled trial of the effect of an advanced cookstove intervention on pneumonia in children under the age of 5 years (under 5s) in Malawi (www.capstudy.org). The primary outcome of the trial is the incidence of pneumonia during a two-year follow-up period, as diagnosed by healthcare providers who are using the World Health Organization (WHO) integrated management of childhood illnesses (IMCI) pneumonia assessment protocol and who are blinded to the trial arms. We evaluated the quality of pneumonia assessment in under 5s in this setting via a cross sectional study of provider-patient encounters at nine outpatient clinics located within the catchment area of 150 village-level clusters enrolled in the trial across the two study locations of Chikhwawa and Karonga, Malawi, between May and June 2015 using the IMCI guidelines as a benchmark. Data were collected using a key equipment checklist, an IMCI pneumonia knowledge test, and a clinical evaluation checklist. The median number of key equipment items available was 6 (range 4 to 7) out of a possible 7. The median score on the IMCI pneumonia knowledge test among 23 clinicians was 75% (range 60% to 89%). Among a total of 176 consultations performed by 15 clinicians, a median of 9 (range 3 to 13) out of 13 clinical evaluation tasks were performed. Overall, the clinicians were adequately equipped for the assessment of sick children, had good knowledge of the IMCI guidelines, and conducted largely thorough clinical evaluations. We recommend the simple pragmatic approach to quality assurance described herein for similar studies conducted in challenging research settings. PMID- 27187774 TI - Video-Assisted Thoracoscopic Sympathectomy for Palmar Hyperhidrosis: A Meta Analysis of Randomized Controlled Trials. AB - OBJECTIVES: Video-assisted thoracoscopic sympathectomy (VTS) is effective in treating palmar hyperhidrosis (PH). However, it is no consensus over which segment should undergo VTS to maximize efficacy and minimize the complications of compensatory hyperhidrosis (CH). This study was designed to compare the efficiency and side effects of VTS of different segments in the treatment of PH. METHODS: A comprehensive search of PubMed, Ovid MEDLINE, EMBASE, Web of Science, ScienceDirect, the Cochrane Library, Scopus and Google Scholar was performed to identify studies comparing VTS of different segments for treatment of PH. The data was analyzed by Revman 5.3 software and SPSS 18.0. RESULTS: A total of eight randomized controlled trials (RCTs) involving 1200 patients were included. Meta analysis showed that single segment/low segments VTS could reduce the risk of moderate/severe CH compared with multiple segments/high segments. The risk of total CH had a similar trend. In the subgroup analysis of single segment VTS, no significant differences were found between T2/T3 VTS and other segments in postoperative CH and degree of CH. T4 VTS showed better efficacy in limiting CH compared with other segments. CONCLUSIONS: T4 appears to be the best segment for the surgical treatment of PH. Our findings require further validation in more high-quality, large-scale randomized controlled trials. PMID- 27187776 TI - First report of charge-transfer induced heat-set hydrogel. Structural insights and remarkable properties. AB - The remarkable ability of a charge-transfer (CT) complex prepared from a pyrene based donor (Py-D) and a naphthalenediimide-based acceptor (NDI-A) led to the formation of a deep-violet in color, transparent hydrogel at room temperature (RT gel). Simultaneously, the RT-gel was diluted beyond its critical gelator concentration (CGC) to obtain a transparent sol. Very interestingly, the resultant sol, on heating above 70 degrees C, transformed into a heat-set gel instantaneously with a hitherto unknown CGC value. Detailed studies revealed the smaller globular aggregates of the RT-gels fuse to form giant globules upon heating, which, in turn, resulted in heat-set gelation through further aggregation. The thermoresponsive property of Py-D alone and 1 : 1 Py-D : NDI-A CT complex was investigated in detail which revealed the hydrophobic collapse of the oxyethylene chains of the CT complex upon heating was mainly responsible for heat-set gelation. Thixotropy, injectability, as well as stimuli responsiveness of the RT-gels were also addressed. In contrast, heat-set gel did not show thixotropic behavior. The X-ray diffraction (XRD) patterns of the xerogel depicted lamellar packing of the CT stacks in the gel phase. Single crystal XRD studies further evidenced the 1 : 1 mixed CT stack formation in the lamellae and also ruled out orthogonal hydrogen bonding possibilities among the hydrazide unit in the CT gel although such interaction was observed in a single crystal of NDI-A alone. In addition, a Ag(+)-ion triggered metallogelation of NDI-A and nematic liquid-crystalline property of Py-D were also observed. PMID- 27187775 TI - Burnout syndrome in first to sixth-year medical students at a private university in the north of Mexico: descriptive cross-sectional study. AB - INTRODUCTION: Burnout syndrome is a three-dimensional clinical syndrome caused by stress at work. It is frequent in professions which require direct contact with people. In Mexico, the presence of Burnout Syndrome in doctors and medical students, is characterized as a threat to their health, quality of life and professional performance. OBJECTIVES: To evaluate the prevalence of burnout syndrome in students of years 1 through 6 of medical school at a private university in northern Mexico. METHODS: Cross-sectional study in the Escuela de Medicina Campus Laguna de la Universidad Autonoma de Durango. The one-dimensional scale of Burnout Student (EUBE) and the Maslach Burnout Inventory (MBI) were applied to the participants. SPSS 19 was used to analyze the data. RESULTS: Of the 344 students, 255 participated; 153 from years 1 to 3 (group 1); and 72 from years 4 to 6 (group 2). We found that 94.1% of the students of group 1 had mild burnout syndrome, and 2.8% had moderate burnout syndrome. In Group 2, 27.8% had moderate burnout syndrome, and 8.3% had severe burnout syndrome. The prevalence of severe burnout syndrome was higher in group 2 than in group 1 (p=0.02). CONCLUSIONS: Burnout syndrome affects medical students across all stages of their studies, and develops in a progressive way. In our study, external factors have no influence on the development of burnout syndrome. PMID- 27187777 TI - What Is the Effect on Obesity Indicators from Replacing Prolonged Sedentary Time with Brief Sedentary Bouts, Standing and Different Types of Physical Activity during Working Days? A Cross-Sectional Accelerometer-Based Study among Blue Collar Workers. AB - INTRODUCTION: The aim of the study was to investigate if (a) substituting total sedentary time or long sedentary bouts with standing or various types of physical activity and (b) substituting long sedentary bouts with brief sedentary bouts; is associated with obesity indicators using a cross sectional isotemporal substitution approach among blue-collar workers. METHODS: A total of 692 workers from transportation, manufacturing and cleaning sectors wore an Actigraph GT3X+ accelerometer on the thigh for 1-4 working days. The sedentary (sit and lie), standing, walking, and moderate to vigorous physical activity (MVPA) time on working days was computed using validated Acti4 software. The total sedentary time and uninterrupted sedentary time spent in brief (<=5 mins), moderate (>5 and <=30 mins), and long (>30mins) bouts, were determined for the whole day and during work and non-work time separately. The obesity indicators, BMI (kg/m2), waist circumference (cm) and fat percentage were objectively measured. Isotemporal substitution modelling was utilized to determine the linear association with obesity indicators of replacing 30 min of total sedentary time or long sedentary bouts with standing, walking or MVPA and separately replacing 30 min of long sedentary bouts with brief sedentary bouts. RESULTS: Workers [mean (standard deviation, SD); age = 45.1 (9.9) years, BMI = 27.5 (4.9) kg/m2, %BF = 29.6 (9.5), waist circumference = 94.4 (13.0) cm] sat for 2.4 hours (~32% of the measured time, SD = 1.8 hours) across the day during work period and 5.5 hours (~62% of the measured time, SD = 1.5 hours) during non-work period. Most of the sedentary time was accrued in moderate bouts [work = 1.40 (SD = 1.09) hours] during work and in long bouts during non-work [2.7 (SD = 1.4) hours], while least in long sedentary bouts during work [work = 0.5 (SD = 0.9)] and in brief sedentary bouts [0.5 hours (SD = 0.3)] during non-work. Significant associations with all obesity indicators were found when 30 min of total sedentary time or long sedentary bouts were replaced with standing time (~1-2% lower) or MVPA (~4 9% lower) during whole day, work, and non-work periods. The exception was that a statistically significant association was not observed with any obesity indicator when replacing total sedentary time or long sedentary bouts with standing time during the work period. Significant beneficial associations were found when replacing the long sedentary bouts with brief sedentary bouts (~3-5% lower) during all domains. CONCLUSION: Replacing total sedentary time and long sedentary bouts, respectively, not only with MVPA but also standing time appears to be beneficially associated with obesity indicators among blue-collar workers. Additionally, replacing long sedentary bouts with brief sedentary bouts was also beneficially associated with obesity indicators. Studies using prospective design are needed to confirm the findings. PMID- 27187778 TI - Assessment of the Tumor Redox Status in Head and Neck Cancer by 62Cu-ATSM PET. AB - PURPOSE: Tumor redox is an important factor for cancer progression, resistance to treatments, and a poor prognosis. The aim of the present study was to define tumor redox (over-reduction) using 62Cu-diacetyl-bis(N4-methylthiosemicarbazone) (62Cu-ATSM) PET and compare its prognostic potential in head and neck cancer (HNC) with that of 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG). METHODS: Thirty HNC patients (stage II-IV) underwent pretreatment 62Cu-ATSM and 18F-FDG PET scans. Maximum standardized uptake values (SUVATSM and SUVFDG) and tumor-to-muscle activity concentration ratios (TMRATSM and TMRFDG) were measured. Reductive-tumor volume (RTV) was then determined at four thresholds (40%, 50%, 60%, and 70% SUVATSM), and total-lesion-reduction (TLR) was calculated as the product of the mean SUV and RTV for 62Cu-ATSM. In 18F-FDG, metabolic-tumor-volume (MTV) and total-lesion-glycolysis (TLG) were obtained at a threshold of 40%. A ROC analysis was performed to determine % thresholds for RTV and TLR showing the best predictive performance, and these were then used to determine the optimal cut-off values to stratify patients for each parameter. Progression-free-survival (PFS) and cause-specific-survival (CSS) were evaluated by the Kaplan-Meier method. RESULTS: The means +/- standard deviations of PFS and CSS periods were 16.4+/ 13.4 and 19.2+/-12.4 months, respectively. A ROC analysis determined that the 70% SUVATSM threshold for RTV and TLR was the best for predicting disease progression and cancer death. Optimal cut-offs for each index were SUVATSM = 3.6, SUVFDG = 7.9, TMRATSM = 3.2, TMRFDG = 5.6, RTV = 2.9, MTV = 8.1, TLR = 14.0, and TLG = 36.5. When the cut-offs for TMRATSM and TLR were set as described above in 62Cu ATSM PET, patients with higher TMRATSM (p = 0.03) and greater TLR (p = 0.02) showed significantly worse PFS, while patients with greater TLR had significantly worse CSS (p = 0.02). Only MTV in 18F-FDG PET predicted differences in PSF and CSS (p = 0.03 and p = 0.03, respectively). CONCLUSION: Tumor redox parameters measured by 62Cu-ATSM PET may be determinants of HNC patient outcomes and help define optimal patient-specific treatments. PMID- 27187779 TI - Polyurethane Ionophore-Based Thin Layer Membranes for Voltammetric Ion Activity Sensing. AB - We report on a plasticized polyurethane ionophore-based thin film material (of hundreds of nanometer thickness) for simultaneous voltammetric multianalyte ion activity detection triggered by the oxidation/reduction of an underlying poly(3 octylthiophene) film. This material provides excellent mechanical, physical, and chemical robustness compared to other polymers. Polyurethane films did not exhibit leaching of lipophilic additives after rinsing with a direct water jet and exhibited resistance to detachment from the underlying electrode surface, resulting in a voltammetric current response with less than <1.5% RSD variation (n = 50). In contrast, plasticized poly(vinyl chloride), polystyrene, and poly(acrylate) ionophore-based membranes of the same thickness and composition exhibited a significant deterioration of the signal after identical treatment. While previously reported works emphasized fundamental advancement of multi-ion detection with multi-ionophore-based thin films, polyurethane thin membranes allow one to achieve real world measurements without sacrificing analytical performance. Indeed, polyurethane membranes are demonstrated to be useful for the simultaneous determination of potassium and lithium in undiluted human serum and blood with attractive precision. PMID- 27187780 TI - Posttraumatic Stress in Parents of Children Diagnosed with Cancer: Hyperarousal and Avoidance as Mediators of the Relationship between Re-Experiencing and Dysphoria. AB - BACKGROUND: Increased understanding of the relationships between different symptom clusters involved in posttraumatic stress symptoms (PTSS) could guide empirical research and clinical practice. The objective of the present study was to investigate whether hyperarousal and avoidance mediated the relationship between re-experiencing and dysphoria in parents of children diagnosed with cancer. METHODS: Longitudinal data from parents of children receiving cancer therapy were used. PTSS were assessed using the PTSD Checklist Civilian Version at one week (T1), two (T2) and four months (T3) after diagnosis. Mediation analyses for multiple mediators were conducted for mothers (n = 122) and fathers (n = 121), respectively. The mediation model tested the assumption that the PTSS symptom clusters hyperarousal and avoidance mediated the relationship between re experiencing and dysphoria. RESULTS: For fathers, none of the hypothesized mediators were significant. For mothers, hyperarousal mediated the relationship between re-experiencing and dysphoria, but avoidance did not. CONCLUSIONS: Results suggest that hyperarousal is important for the development of dysphoria in mothers, supporting use of interventions targeting such symptoms in the early and ongoing period following the child's diagnosis. PMID- 27187781 TI - Diverse Empirical Evidence on Epidemiological Transition in Low- and Middle Income Countries: Population-Based Findings from INDEPTH Network Data. AB - BACKGROUND: Low- and middle-income countries are often described as being at intermediate stages of epidemiological transition, but there is little population based data with reliable cause of death assignment to examine the situation in more detail. Non-communicable diseases are widely seen as a coming threat to population health, alongside receding burdens of infection. The INDEPTH Network has collected empirical population data in a number of health and demographic surveillance sites in low- and middle-income countries which permit more detailed examination of mortality trends over time. OBJECTIVE: To examine cause-specific mortality trends across all ages at INDEPTH Network sites in Africa and Asia during the period 1992-2012. Emphasis is given to the 15-64 year age group, which is the main focus of concern around the impact of the HIV pandemic and emerging non-communicable disease threats. METHODS: INDEPTH Network public domain data from 12 sites that each reported at least five years of cause-specific mortality data were used. Causes of death were attributed using standardised WHO verbal autopsy methods, and mortality rates were standardised for comparison using the INDEPTH standard population. Annual changes in mortality rates were calculated for each site. RESULTS: A total of 96,255 deaths were observed during 9,487,418 person years at the 12 sites. Verbal autopsies were completed for 86,039 deaths (89.4%). There were substantial variations in mortality rates between sites and over time. HIV-related mortality played a major part at sites in eastern and southern Africa. Deaths in the age group 15-64 years accounted for 43% of overall mortality. Trends in mortality were generally downwards, in some cases quite rapidly so. The Bangladeshi sites reflected populations at later stages of transition than in Africa, and were largely free of the effects of HIV/AIDS. CONCLUSIONS: To some extent the patterns of epidemiological transition observed followed theoretical expectations, despite the impact of the HIV pandemic having a major effect in some locations. Trends towards lower overall mortality, driven by decreasing infections, were the general pattern. Low- and middle-income country populations appear to be in an era of rapid transition. PMID- 27187783 TI - Comparative Safety of Pharmacologic Treatments for Persistent Depressive Disorder: A Systematic Review and Network Meta-Analysis. AB - We aimed to compare the safety of antidepressants for the treatment of persistent depressive disorder (PDD) with each other and with placebo. We conducted a systematic electronic search and included randomized controlled trials that investigated antidepressants for the treatment of PDD in adults. Outcomes were the incidence of experiencing any adverse event, specific adverse events and related treatment discontinuations. We analyzed the data using traditional and network meta-analyses. Thirty-four studies that comprised 4,769 patients and examined 20 individual agents in nine substance classes were included. Almost all analyzed substance classes were associated with higher discontinuation rates than placebo including tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), antipsychotics, and the serotonin antagonist and reuptake inhibitor (SARI) trazodone. The odds of experiencing any adverse event were significantly higher for TCAs and serotonin noradrenaline reuptake inhibitors (SNRIs) compared to placebo. Pairwise comparisons among the substance classes revealed that more patients receiving TCAs or SNRIs experienced any adverse event and that more patients receiving TCAs or the SARI trazodone discontinued treatment. The complementary treatment with acetyl-l-carnitine showed lower rates of experiencing any adverse event and related discontinuations than all other comparators. TCAs were primarily associated with (anti-)cholinergic and sedating adverse events. SSRIs primarily showed gastrointestinal adverse events. Patients treated with the antipsychotic amisulpride were more likely to manifest weight gain and endocrine adverse events. The comparative evidence for further agents was insufficient or lacking. The identified safety differences may be used to inform the selection among the antidepressants. PMID- 27187784 TI - Capture of Tumor Cells on Anti-EpCAM-Functionalized Poly(acrylic acid)-Coated Surfaces. AB - The presence of tumor cells in blood is predictive of short survival in several cancers and their isolation and characterization can guide toward the use of more effective treatments. These circulating tumor cells (CTC) are, however, extremely rare and require a technology that is sufficiently sensitive and specific to identify CTC against a background of billions of blood cells. Immuno-capture of cells expressing the epithelial cell adhesion molecule (EpCAM) are frequently used to enrich CTC from blood. The choice of bio conjugation strategy and antibody clone is crucial for adequate cell capture but is poorly understood. In this study, we determined the binding affinity constants and epitope binding of the EpCAM antibodies VU1D-9, HO-3, EpAb3-5, and MJ-37 by surface plasmon resonance imaging (SPRi). Glass surfaces were coated using a poly(acrylic acid) based coating and functionalized with anti-EpCAM antibodies. Binding of cells from the breast carcinoma cell line (SKBR-3) to the functionalized surfaces were compared. Although EpAb3-5 displayed the highest binding affinity HO-3 captured the highest amount of cells. Hence we report differences in the performance of the different antibodies and more importantly that the choice of antibody to capture CTC should be based on multiple assays. PMID- 27187785 TI - Safety considerations when treating myelofibrosis. AB - INTRODUCTION: Myelofibrosis (MF) is a clonal disorder leading to marrow fibrosis, cytopenias and extramedullary haematopoiesis. AREAS COVERED: Generic management of MF with a specific focus on the efficacy and safety profile of the Janus Kinase (JAK)1/JAK 2 kinase inhibitor, ruxolitinib (Novartis Pharmaceuticals, Basel, Switzerland), will be discussed. This agent has manageable haematological side effects and possesses both beneficial and potentially detrimental immunosuppressive effects. Multiple JAK inhibitors are in various stages of development but some have been withdrawn due to unexpected toxicities such as the occurrence of Wernicke's encephalopathy (Fedratinib; Sanofi, Paris). Traditional therapies such as hydroxycarbamide, interferon, immunomodulatory drugs and androgens will also be discussed. EXPERT OPINION: Therapeutic options in MF have expanded with the introduction of JAK inhibitors. Ruxolitinib benefits many patients with symptomatic MF. Other JAK inhibitors such as momelotinib may have the additional benefit of alleviating anaemia. Unfortunately, there is no current JAK inhibitor option for patients with severe thrombocytopenia as pacritinib was recently put on clinical hold due to adverse events. Careful consideration needs to be given towards optimal management of patients who lose their response/are resistant to JAK inhibitor therapies and those with a high risk mutational status but lower risk prognostic score. PMID- 27187786 TI - The effect of the synthetic route on the structural, textural, morphological and catalytic properties of iron(iii) oxides and oxyhydroxides. AB - A variety of iron(iii) oxides and oxyhydroxides were synthesised and characterised using three distinct methods of preparation: microemulsion, precipitation and sol-gel. The results clearly showed that the structure, textural properties, crystal morphology and catalytic performance of the phases obtained were highly dependent on the chemical routes used for the synthesis. Precipitation and microemulsion methods allowed obtaining mesoporous nanostructured iron(iii) oxides with mean particle sizes of 4 nm (amorphous hematite) and 7 nm (ferrihydrite), which exhibited a high surface area (291.4 m(2) g(-1) and 192.3 m(2) g(-1), respectively) and a very good catalytic behaviour in the advanced oxidation of highly non-biodegradable wastewaters. The different conditions employed in the synthesis of these materials through the sol gel method yielded two goethites with practically the same catalytic properties, but dissimilar morphologies and texture. When soft agitation and slow addition of the precipitating agent were used, the resulting material (G1) was made up of shorter and finer particles, markedly acicular, with an average length of 400 +/- 50 nm and width of 15 +/- 5 nm. However, vigorous agitation and rapid addition of the precipitating agent led to the formation of longer and coarser particles, moderately acicular, the average length and width being 950 +/- 100 nm and 140 +/ 20 nm, respectively. The use of the sol-gel technique also resulted in the formation of a solid consisting of a mixture of hematite as the main crystalline phase and goethite particles dispersed among the hematite particles. This solid presented a low specific surface area (13.2 m(2) g(-1)) and lower catalytic activity. Therefore, precipitation and microemulsion proved to be the most suitable techniques to synthesise catalytically active disordered iron(iii) oxide nanoparticles, due to the presence of highly reactive non-stoichiometric iron(iii) ions, a higher surface area and smaller particle sizes. PMID- 27187782 TI - Estimating the Risk of Chronic Pain: Development and Validation of a Prognostic Model (PICKUP) for Patients with Acute Low Back Pain. AB - BACKGROUND: Low back pain (LBP) is a major health problem. Globally it is responsible for the most years lived with disability. The most problematic type of LBP is chronic LBP (pain lasting longer than 3 mo); it has a poor prognosis and is costly, and interventions are only moderately effective. Targeting interventions according to risk profile is a promising approach to prevent the onset of chronic LBP. Developing accurate prognostic models is the first step. No validated prognostic models are available to accurately predict the onset of chronic LBP. The primary aim of this study was to develop and validate a prognostic model to estimate the risk of chronic LBP. METHODS AND FINDINGS: We used the PROGRESS framework to specify a priori methods, which we published in a study protocol. Data from 2,758 patients with acute LBP attending primary care in Australia between 5 November 2003 and 15 July 2005 (development sample, n = 1,230) and between 10 November 2009 and 5 February 2013 (external validation sample, n = 1,528) were used to develop and externally validate the model. The primary outcome was chronic LBP (ongoing pain at 3 mo). In all, 30% of the development sample and 19% of the external validation sample developed chronic LBP. In the external validation sample, the primary model (PICKUP) discriminated between those who did and did not develop chronic LBP with acceptable performance (area under the receiver operating characteristic curve 0.66 [95% CI 0.63 to 0.69]). Although model calibration was also acceptable in the external validation sample (intercept = -0.55, slope = 0.89), some miscalibration was observed for high-risk groups. The decision curve analysis estimated that, if decisions to recommend further intervention were based on risk scores, screening could lead to a net reduction of 40 unnecessary interventions for every 100 patients presenting to primary care compared to a "treat all" approach. Limitations of the method include the model being restricted to using prognostic factors measured in existing studies and using stepwise methods to specify the model. Limitations of the model include modest discrimination performance. The model also requires recalibration for local settings. CONCLUSIONS: Based on its performance in these cohorts, this five-item prognostic model for patients with acute LBP may be a useful tool for estimating risk of chronic LBP. Further validation is required to determine whether screening with this model leads to a net reduction in unnecessary interventions provided to low-risk patients. PMID- 27187788 TI - A Catalytic Peterson-like Synthesis of Alkenyl Nitriles. AB - A heterogeneous fluoride catalyst was found to enable the straightforward formation of alkenyl nitriles from the reaction of aldehydes and simple or substituted acetonitriles, in the presence of commercially available silazanes and in solvent-free conditions. The protocol afforded the products in good to excellent yields with selectivity values dependent on the nature of the substrates. It represents an alternative to classic approaches using stoichiometric strong bases, and the catalyst can be easily recovered and reused for consecutive cycles. PMID- 27187789 TI - Conceptual clarifications regarding Chilean Act 20850 on public funding of high cost diseases. AB - In 2015, Chile enacted the 20850 law, providing public funds for rare and costly diseases that demanded high diagnostic and therapeutic expenditures. The law modifies the Chilean Sanitary Code regulation of research with human beings, aiming at the protection of subjects by securing post-investigational medical benefits and insurance coverage for damage imputable to the research they participated in. Due to ambiguous phrasing, a polemic rose for fear that these protective measures applied to all clinical research, although a careful reading of the law in its context clearly suggests that it refers to phase I therapeutic trials. This paper stresses the distinction between compassionate use and genuine phase I/II therapeutic trials aimed at both pharmacodynamics and an intended therapeutic effect for severe and progressive diseases that are therapeutically orphaned, emphasizing the ethical and medical duty of providing post-trial beneficial medication. PMID- 27187790 TI - Transport studies in 2D transition metal dichalcogenides and black phosphorus. AB - Two-dimensional (2D) materials are a new family of materials with interesting physical properties, ranging from insulating hexagonal boron nitride, semiconducting or semi-metallic transition metal dichalcogenides, to gapless metallic graphene. In this review, we provide a brief discussion of transport studies in transition metal dichalcogenides, including both semiconducting and semi-metallic phases, as well as a discussion of the newly emerged narrow bandgap layered material, black phosphorus, in terms of its electrical and quantum transport properties at room and cryogenic temperatures. Ultra-thin layered channel materials with atomic layer thickness in the cross-plane direction, together with relatively high carrier mobility with appropriate passivation techniques, provide the promise for new scientific discoveries and broad device applications. PMID- 27187787 TI - Tgif1 and Tgif2 Regulate Axial Patterning in Mouse. AB - Tgif1 and Tgif2 are transcriptional repressors that inhibit the transcriptional response to transforming growth factor beta signaling, and can repress gene expression by direct binding to DNA. Loss of function mutations in TGIF1 are associated with holoprosencephaly (HPE) in humans. In mice, embryos lacking both Tgif1 and Tgif2 fail to complete gastrulation, and conditional double null embryos that survive past gastrulation have HPE and do not survive past mid gestation. Here we show that in mice of a relatively pure C57BL/6 strain background, loss of Tgif1 alone results in defective axial patterning and altered expression of Hoxc6. The primary defects in Tgif1 null embryos are the presence of extra ribs on the C7 vertebra, consistent with a posterior transformation phenotype. In addition we observed defective cervical vertebrae, primarily C1-C5, in both adult mice and embryos that lacked Tgif1. The combination of Tgif1 and Tgif2 mutations increases the severity and penetrance of the posterior transformation phenotype, without altering the type of defects seen. Similarly, exposure of Tgif1 mutant embryos to retinoic acid at E8.5 increased the severity and penetrance of the Tgif1 phenotype. This suggests that Tgif1 and Tgif2 regulate axial patterning and that reduced TGIF function sensitizes embryos to the effects of retinoic acid. PMID- 27187792 TI - Nanoemulsion: for improved oral delivery of repaglinide. AB - Repaglinide (RPG) is a fast-acting prandial glucose regulator. It acts by stimulating insulin release from pancreatic beta-cells. Recurrent dosing of RPG before each meal is burdensome remedy. Hence the plan of the present study was to evaluate nanoemulsion as a hopeful carrier for RPG for persistent hypoglycemic effect. The drug was incorporated into oil phase of nanoemulsion to give improved biopharmaceutical properties as compared to the lipid-based systems. Pseudo ternary phase diagrams were prepared by aqueous titration method. Formulations were selected at a difference of 5% w/w of oil from the o/w nanoemulsion region of phase diagrams. The optimized nanoemulsion formulation constituted sefsol-218 (5% v/v) as an oil phase, 30% v/v of Tween-80 and transcutol as a surfactant and co-surfactant to restrain nanodroplet size and low viscosity and distilled water (65%). In vitro dissolution studies showed higher drug release (98.22%), finest droplet size (76.23 nm), slightest polydispersity value (0.183), least viscosity (21.45 cps) and immeasurable dilution capability from the nanoemulsion as compared with existing oral tablet formulation. The optimized RPG nanoemulsion formulation showed better hypoglycemic effect in comparison to tablet formulation in experimental diabetic rats. No significant variations were also observed in the optimized formulation when subjected to accelerated stability study at different temperature and relative humidity over a period of 3 months. PMID- 27187791 TI - Functional Green-Tuned Proteorhodopsin from Modern Stromatolites. AB - The sequenced genome of the poly-extremophile Exiguobacterium sp. S17, isolated from modern stromatolites at Laguna Socompa (3,570 m), a High-Altitude Andean Lake (HAAL) in Argentinean Puna revealed a putative proteorhodopsin-encoding gene. The HAAL area is exposed to the highest UV irradiation on Earth, making the microbial community living in the stromatolites test cases for survival strategies under extreme conditions. The heterologous expressed protein E17R from Exiguobacterium (248 amino acids, 85% sequence identity to its ortholog ESR from E. sibiricum) was assembled with retinal displaying an absorbance maximum at 524 nm, which makes it a member of the green-absorbing PR-subfamily. Titration down to low pH values (eventually causing partial protein denaturation) indicated a pK value between two and three. Global fitting of data from laser flash-induced absorption changes gave evidence for an early red-shifted intermediate (its formation being below the experimental resolution) that decayed (tau1 = 3.5 MUs) into another red-shifted intermediate. This species decayed in a two-step process (tau2 = 84 MUs, tau3 = 11 ms), to which the initial state of E17-PR was reformed with a kinetics of 2 ms. Proton transport capability of the HAAL protein was determined by BLM measurements. Additional blue light irradiation reduced the proton current, clearly identifying a blue light absorbing, M-like intermediate. The apparent absence of this intermediate is explained by closely matching formation and decay kinetics. PMID- 27187793 TI - Chronic dietary exposure to pesticide residues and associated risk in the French ELFE cohort of pregnant women. AB - Dietary exposure to pesticide residues may present a risk to public health, especially for sensitive populations such as pregnant women. To characterize this risk, this study assessed chronic dietary exposure to pesticide residues based on the French ELFE cohort. A self-administered food frequency questionnaire (FFQ) about the last three months of pregnancy filled in by pregnant women in 2011 was used in combination with occurrence data from French Total Diet Studies completed by the results of national monitoring programs on pesticide residues in food. The dietary intake of pesticides (MUg/kg of body weight/day) was estimated for 14,099 pregnant women with a complete FFQ, for 317 substances under two occurrence scenarios to handle left-censored data: a lower-bound scenario (LB), where undetected results were set to zero, and an upper-bound scenario (UB), where undetected results were set to the detection limit if the substance was expected to be found in food and zero if it was not. The risk was assessed for 284 substances with a toxicological reference value (TRV) and a good coverage level of the diet potentially contributing to pesticide intake. The cumulative risk was also assessed for seven effects on nervous and thyroid systems using the hazard index and the Cumulative Assessment Groups defined by EFSA. Substances with the highest exposure levels under the LB scenario were, in decreasing order, imazalil, piperonyl butoxide, chlorpropham, thiabendazole, iprodione and propargite. Under the LB scenario, only for lindane did women have a statistically significant probability of exceeding the TRV (2.4%). Under the UB scenario, risk could not be excluded for nine other substances. A better management of left-censored data and more sensitive analyses of the main food contributors might help to refine the UB exposure and risk assessments. A statistically significant cumulative risk was found for neurochemical effects related to high intake levels of three organophosphate insecticides (chlorpyrifos, pirimiphos-methyl and dimethoate) mainly detected in fruits and cereals. PMID- 27187794 TI - Regulation of infection efficiency in a globally abundant marine Bacteriodetes virus. AB - Bacteria impact humans, industry and nature, but do so under viral constraints. Problematically, knowledge of viral infection efficiencies and outcomes derives from few model systems that over-represent efficient lytic infections and under represent virus-host natural diversity. Here we sought to understand infection efficiency regulation in an emerging environmental Bacteroidetes-virus model system with markedly different outcomes on two genetically and physiologically nearly identical host strains. For this, we quantified bacterial virus (phage) and host DNA, transcripts and phage particles throughout both infections. While phage transcriptomes were similar, transcriptional differences between hosts suggested host-derived regulation of infection efficiency. Specifically, the alternative host overexpressed DNA degradation genes and underexpressed translation genes, which seemingly targeted phage DNA particle production, as experiments revealed they were both significantly delayed (by >30 min) and reduced (by >50%) in the inefficient infection. This suggests phage failure to repress early alternative host expression and stress response allowed the host to respond against infection by delaying phage DNA replication and protein translation. Given that this phage type is ubiquitous and abundant in the global oceans and that variable viral infection efficiencies are central to dynamic ecosystems, these data provide a critically needed foundation for understanding and modeling viral infections in nature. PMID- 27187795 TI - Contribution of ammonia oxidation to chemoautotrophy in Antarctic coastal waters. AB - There are few measurements of nitrification in polar regions, yet geochemical evidence suggests that it is significant, and chemoautotrophy supported by nitrification has been suggested as an important contribution to prokaryotic production during the polar winter. This study reports seasonal ammonia oxidation (AO) rates, gene and transcript abundance in continental shelf waters west of the Antarctic Peninsula, where Thaumarchaeota strongly dominate populations of ammonia-oxidizing organisms. Higher AO rates were observed in the late winter surface mixed layer compared with the same water mass sampled during summer (mean+/-s.e.: 62+/-16 versus 13+/-2.8 nm per day, t-test P<0.0005). AO rates in the circumpolar deep water did not differ between seasons (21+/-5.7 versus 24+/ 6.6 nm per day; P=0.83), despite 5- to 20-fold greater Thaumarchaeota abundance during summer. AO rates correlated with concentrations of Archaea ammonia monooxygenase (amoA) genes during summer, but not with concentrations of Archaea amoA transcripts, or with ratios of Archaea amoA transcripts per gene, or with concentrations of Betaproteobacterial amoA genes or transcripts. The AO rates we report (<0.1-220 nm per day) are ~10-fold greater than reported previously for Antarctic waters and suggest that inclusion of Antarctic coastal waters in global estimates of oceanic nitrification could increase global rate estimates by ~9%. Chemoautotrophic carbon fixation supported by AO was 3-6% of annualized phytoplankton primary production and production of Thaumarchaeota biomass supported by AO could account for ~9% of the bacterioplankton production measured in winter. Growth rates of thaumarchaeote populations inferred from AO rates averaged 0.3 per day and ranged from 0.01 to 2.1 per day. PMID- 27187796 TI - Biogeography of sulfur-oxidizing Acidithiobacillus populations in extremely acidic cave biofilms. AB - Extremely acidic (pH 0-1.5) Acidithiobacillus-dominated biofilms known as snottites are found in sulfide-rich caves around the world. Given the extreme geochemistry and subsurface location of the biofilms, we hypothesized that snottite Acidithiobacillus populations would be genetically isolated. We therefore investigated biogeographic relationships among snottite Acidithiobacillus spp. separated by geographic distances ranging from meters to 1000s of kilometers. We determined genetic relationships among the populations using techniques with three levels of resolution: (i) 16S rRNA gene sequencing, (ii) 16S-23S intergenic transcribed spacer (ITS) region sequencing and (iii) multi-locus sequencing typing (MLST). We also used metagenomics to compare functional gene characteristics of select populations. Based on 16S rRNA genes, snottites in Italy and Mexico are dominated by different sulfur-oxidizing Acidithiobacillus spp. Based on ITS sequences, Acidithiobacillus thiooxidans strains from different cave systems in Italy are genetically distinct. Based on MLST of isolates from Italy, genetic distance is positively correlated with geographic distance both among and within caves. However, metagenomics revealed that At. thiooxidans populations from different cave systems in Italy have different sulfur oxidation pathways and potentially other significant differences in metabolic capabilities. In light of those genomic differences, we argue that the observed correlation between genetic and geographic distance among snottite Acidithiobacillus populations is partially explained by an evolutionary model in which separate cave systems were stochastically colonized by different ancestral surface populations, which then continued to diverge and adapt in situ. PMID- 27187798 TI - Not All That Glitters Is Gold: Metal-Migration-Induced Degradation in Perovskite Solar Cells. AB - Perovskite solar cells (PSCs) have now achieved efficiencies in excess of 22%, but very little is known about their long-term stability under thermal stress. So far, stability reports have hinted at the importance of substituting the organic components, but little attention has been given to the metal contact. We investigated the stability of state-of-the-art PSCs with efficiencies exceeding 20%. Remarkably, we found that exposing PSCs to a temperature of 70 degrees C is enough to induce gold migration through the hole-transporting layer (HTL), spiro MeOTAD, and into the perovskite material, which in turn severely affects the device performance metrics under working conditions. Importantly, we found that the main cause of irreversible degradation is not due to decomposition of the organic and hybrid perovskite layers. By introducing a Cr metal interlayer between the HTL and gold electrode, high-temperature-induced irreversible long term losses are avoided. This key finding is essential in the quest for achieving high efficiency, long-term stable PSCs which, in order to be commercially viable, need to withstand hard thermal stress tests. PMID- 27187797 TI - Powerful Complex Immunoadjuvant Based on Synergistic Effect of Combined TLR4 and NOD2 Activation Significantly Enhances Magnitude of Humoral and Cellular Adaptive Immune Responses. AB - Binding of pattern recognition receptors (PRRs) by pathogen-associated molecular patterns (PAMPs) activates innate immune responses and contributes to development of adaptive immunity. Simultaneous stimulation of different types of PRRs can have synergistic immunostimulatory effects resulting in enhanced production of molecules that mediate innate immunity such as inflammatory cytokines, antimicrobial peptides, etc. Here, we evaluated the impact of combined stimulation of PRRs from different families on adaptive immunity by generating alum-based vaccine formulations with ovalbumin as a model antigen and the Toll like receptor 4 (TLR4) agonist MPLA and the Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) agonist MDP adsorbed individually or together on the alum-ovalbumin particles. Multiple in vitro and in vivo readouts of immune system activation all showed that while individual PRR agonists increased the immunogenicity of vaccines compared to alum alone, the combination of both PRR agonists was significantly more effective. Combined stimulation of TLR4 and NOD2 results in a stronger and broader transcriptional response in THP-1 cells compared to individual PRR stimulation. Immunostimulatory composition containing both PRR agonists (MPLA and MDP) in the context of the alum-based ovalbumin vaccine also enhanced uptake of vaccine particles by bone marrow derived dendritic cells (BMDCs) and promoted maturation (up-regulation of expression of CD80, CD86, MHCII) and activation (production of cytokines) of BMDCs. Finally, immunization of mice with vaccine particles containing both PRR agonists resulted in enhanced cellular immunity as indicated by increased proliferation and activation (IFN-gamma production) of splenic CD4+ and CD8+ T cells following in vitro restimulation with ovalbumin and enhanced humoral immunity as indicated by higher titers of ovalbumin-specific IgG antibodies. These results indicate that combined stimulation of TLR4 and NOD2 receptors dramatically enhances activation of both the humoral and cellular branches of adaptive immunity and suggests that inclusion of agonists of these receptors in standard alum-based adjuvants could be used to improve the effectiveness of vaccination. PMID- 27187799 TI - Protein-Framed Multi-Porphyrin Micelles for a Hybrid Natural-Artificial Light Harvesting Nanosystem. AB - A micelle-like hybrid natural-artificial light-harvesting nanosystem was prepared through protein-framed electrostatic self-assembly of phycocyanin and a four armed porphyrin star polymer. The nanosystem has a special structure of pomegranate-like unimolecular micelle aggregate with one phycocyanin acceptor in the center and multiple porphyrin donors in the shell. It can inhibit donor self quenching effectively and display efficient transfer of excitation energy (about 80.1 %) in water. Furthermore, the number of donors contributing to a single acceptor could reach as high as about 179 in this nanosystem. PMID- 27187800 TI - Three-Dimensional Reconstruction of the Bony Nasolacrimal Canal by Automated Segmentation of Computed Tomography Images. AB - OBJECTIVE: To apply a fully automated method to quantify the 3D structure of the bony nasolacrimal canal (NLC) from CT scans whereby the size and main morphometric characteristics of the canal can be determined. DESIGN: Cross sectional study. SUBJECTS: 36 eyes of 18 healthy individuals. METHODS: Using software designed to detect the boundaries of the NLC on CT images, 36 NLC reconstructions were prepared. These reconstructions were then used to calculate NLC volume. The NLC axis in each case was determined according to a polygonal model and to 2nd, 3rd and 4th degree polynomials. From these models, NLC sectional areas and length were determined. For each variable, descriptive statistics and normality tests (Kolmogorov-Smirnov and Shapiro-Wilk) were established. MAIN OUTCOME MEASURES: Time for segmentation, NLC volume, axis, sectional areas and length. RESULTS: Mean processing time was around 30 seconds for segmenting each canal. All the variables generated were normally distributed. Measurements obtained using the four models polygonal, 2nd, 3rd and 4th degree polynomial, respectively, were: mean canal length 14.74, 14.3, 14.80, and 15.03 mm; mean sectional area 15.15, 11.77, 11.43, and 11.56 mm2; minimum sectional area 8.69, 7.62, 7.40, and 7.19 mm2; and mean depth of minimum sectional area (craniocaudal) 7.85, 7.71, 8.19, and 8.08 mm. CONCLUSION: The method proposed automatically reconstructs the NLC on CT scans. Using these reconstructions, morphometric measurements can be calculated from NLC axis estimates based on polygonal and 2nd, 3rd and 4th polynomial models. PMID- 27187801 TI - Histologic types of gastric cancer among migrants from the former Soviet Union and the general population in Germany: what kind of prevention do we need? AB - OBJECTIVE: The incidence of gastric cancer (GC) is high among migrants from Eastern Europe and Asia, but a detailed picture of disease characteristics is missing. Our study examined the incidence of histologic types among resettlers from the former Soviet Union and the general population in Germany to draw conclusions on risk factors and possible prevention strategies. METHODS: Between 1990 and 2009, all GC diagnoses among a cohort of 18 619 resettlers residing in the Saarland were identified in the Saarland Cancer Registry database. Age standardized incidence rates (ASRs) of the entire Saarland population and standardized incidence ratios (SIRs) of resettlers compared with the Saarland population were calculated for types according to Lauren. In addition, ASRs and SIRs were modeled using Poisson's regression to investigate time trends. RESULTS: The ASR of intestinal GC in the Saarland population decreased over time, whereas the ASR of diffuse GC remained unchanged. Resettlers' incidence of intestinal GC was elevated among men [SIR: 3.04, 95% confidence interval (CI): 2.05-4.50] and women (SIR: 2.78, 95% CI: 1.61-4.79), whereas diffuse GC was elevated only among women (SIR: 1.98, 95% CI: 1.07-3.69). No time trends for SIRs could be observed in regression analysis. CONCLUSION: Different trends of diffuse GC incidence in Germany and the USA underline the importance of environmental risk factors. The continuously elevated risk of GC among male resettlers is probably associated with risk factors affecting exclusively the intestinal type such as a low intake of fruit and vegetables and heavy alcohol consumption. Future prevention programs for resettlers should include dietary measures. PMID- 27187802 TI - Fabrication of high aspect ratio nanogrid transparent electrodes via capillary assembly of Ag nanoparticles. AB - In this report, we describe the fabrication of periodic Ag nanogrid electrodes by capillary assembly of silver nanoparticles (AgNPs) along patterned nanogrid templates. By assembling the AgNPs into these high-aspect-ratio nanogrid patterns, we can obtain high-aspect-ratio nanogratings, which can overcome the inherent trade-off between the optical transmittance and the sheet resistance of transparent electrodes. The junction resistance between the AgNPs is effectively reduced by photochemical welding and post-annealing. The fabricated high-aspect ratio nanogrid structure with a line width of 150 nm and a height of 450 nm has a sheet resistance of 15.2 Omega sq(-1) and an optical transmittance of 85.4%. PMID- 27187803 TI - The Clinical Challenge of Sepsis Identification and Monitoring. AB - Jean-Louis Vincent outlines why combinations of biomarkers will be central to the future of sepsis diagnosis. PMID- 27187805 TI - A new irregular monoterpene acetate along with eight known compounds with antifungal potential from the aerial parts of Artemisia incisa Pamp (Asteraceae). AB - A new compound named as santolinylol-3-acetate (4-(2-hydroxypropan-2-yl)-2 methylhexa-1,5-dien-3-yl acetate) (3), along with seven known compounds; linoleic acid (1), benzoic acid (2), santolinylol (4), ethyl-(E)-p-hydroxy cinnamate (5), scopoletin (6), esculetin (7) isofraxidin (8) and eupatorin (9), were isolated from the aerial parts (ethanolic extract) of endangered species: Artemisia incisa Pamp (Asteraceae). The compounds' structures were determined through modern spectroscopic techniques, and comparison of data (physicochemical constants) with the literature. The relative stereochemistry of santolinylol-3-acetate (3) was determined by comparing its data of NOESY, and specific rotation with its diol analogue; santolinylol (4), isolated from the same plant; A. incisa. The results of the antifungal activity showed that coumarins are as whole less active compounds. Compounds 3 (25 and 300 MUg/mL), and 4 (12.5 and 300 MUg/mL), showed good activities against Candida albicans, and Aspergillus flavus, respectively, which justifies A. incisa as a traditional medicine for curing the said fungal infections. PMID- 27187806 TI - The Role of Social Workers in Spiritual Care to Facilitate Coping With Chronic Illness and Self-Determination in Advance Care Planning. AB - Spiritual values and beliefs of patients and families influence resilience during chronic illness and shape patient choices during advance care planning. The spiritual needs of Baby Boomers will be more diverse than previous generations, in connection with the questioning, experimental mind-set of this group and the fact that it includes a higher proportion of immigrant populations outside the Judeo-Christian tradition. Social workers are trained explicitly to intervene with diverse populations and are well positioned to offer spiritual support in ways that do not necessarily conform to traditional religions. To the extent of their individual expertise and competence, social workers should assess and provide spiritual care to clients, including those who either are underserved or prefer not to seek assistance from clergy or chaplains because they feel alienated from religious institutions and representatives. They should also be aware of ethical dilemmas in consulting with spiritual care professionals in developing spiritual interventions. Social work education should address clients' humanistic and existential concerns, beliefs and behaviors of the major religions, and forms of nontraditional religious and spiritual experiences; it should also provide experiential opportunities for engaging with grief and earlier advance care planning. There should be attention to different theodical perspectives of the major religions regarding the problem of good and evil, which may preoccupy even clients who no longer participate in organized religion, because these unresolved existential issues may weaken client coping with chronic conditions and may diminish clarity and self-awareness for engaging authentically and effectively in advance care planning. PMID- 27187807 TI - Coencapsulation of alendronate and doxorubicin in pegylated liposomes: a novel formulation for chemoimmunotherapy of cancer. AB - We developed a pegylated liposome formulation of a dissociable salt of a nitrogen containing bisphosphonate, alendronate (Ald), coencapsulated with the anthracycline, doxorubicin (Dox), a commonly used chemotherapeutic agent. Liposome-encapsulated ammonium Ald generates a gradient driving Dox into liposomes, forming a salt that holds both drugs in the liposome water phase. The resulting formulation (PLAD) allows for a high-loading efficiency of Dox, comparable to that of clinically approved pegylated liposomal doxorubicin sulfate (PLD) and is very stable in plasma stability assays. Cytotoxicity tests indicate greater potency for PLAD compared to PLD. This appears to be related to a synergistic effect of the coencapsulated Ald and Dox. PLAD and PLD differed in in vitro monocyte-induced IL-1beta release (greater for PLAD) and complement activation (greater for PLD). A molar ratio Ald/Dox of ~1:1 seems to provide an optimal compromise between loading efficiency of Dox, circulation time and in vivo toxicity of PLAD. In mice, the circulation half-life and tumor uptake of PLAD were comparable to PLD. In the M109R and 4T1 tumor models in immunocompetent mice, PLAD was superior to PLD in the growth inhibition of subcutaneous tumor implants. This new formulation appears to be a promising tool to exploit the antitumor effects of aminobisphosphonates in synergy with chemotherapy. PMID- 27187808 TI - Enhanced Lineage-Specific Differentiation Efficiency of Human Induced Pluripotent Stem Cells by Engineering Colony Dimensionality Using Electrospun Scaffolds. AB - Electrospun scaffolds with varied stiffness promote distinct colony morphology of human induced pluripotent stem cells, which affects their subsequent differentiation. On soft scaffolds, induced pluripotent stem cells develop 3D colonies due to the pliability of the electrospun fibrous networks, leading to greater differentiation tendency to ectodermal lineage. PMID- 27187804 TI - A Model of Yeast Cell-Cycle Regulation Based on a Standard Component Modeling Strategy for Protein Regulatory Networks. AB - To understand the molecular mechanisms that regulate cell cycle progression in eukaryotes, a variety of mathematical modeling approaches have been employed, ranging from Boolean networks and differential equations to stochastic simulations. Each approach has its own characteristic strengths and weaknesses. In this paper, we propose a "standard component" modeling strategy that combines advantageous features of Boolean networks, differential equations and stochastic simulations in a framework that acknowledges the typical sorts of reactions found in protein regulatory networks. Applying this strategy to a comprehensive mechanism of the budding yeast cell cycle, we illustrate the potential value of standard component modeling. The deterministic version of our model reproduces the phenotypic properties of wild-type cells and of 125 mutant strains. The stochastic version of our model reproduces the cell-to-cell variability of wild type cells and the partial viability of the CLB2-dbDelta clb5Delta mutant strain. Our simulations show that mathematical modeling with "standard components" can capture in quantitative detail many essential properties of cell cycle control in budding yeast. PMID- 27187809 TI - Medicare Under Age 65 and Medicaid Patients Have Poorer Bowel Preparations: Implications for Recommendations for an Early Repeat Colonoscopy. AB - BACKGROUND/AIMS: Colonoscopy is performed on patients across a broad spectrum of demographic characteristics. These characteristics may aggregate by patient insurance provider and influence bowel preparation quality and the prevalence of adenomas. The purpose of this study was to evaluate the association of insurance status and suboptimal bowel preparation, recommendation for an early repeat colonoscopy due to suboptimal bowel preparation, adenoma detection rate (ADR), and advanced ADR (AADR). METHODS: This is a cohort study of outpatient colonoscopies (n = 3113) at a single academic medical center. Patient insurance status was categorized into five groups: 1) Medicare < 65y; 2) Medicare >= 65y; 3) Tricare/VA; 4) Medicaid/Colorado Indigent Care Program (CICP); and 5) commercial insurance. We used multivariable logistic or linear regression modeling to estimate the risks for the association between patient insurance and suboptimal bowel preparation, recommendation for an early repeat colonoscopy due to suboptimal bowel preparation, ADR, and AADR. Models were adjusted for appropriate covariates. RESULTS: Medicare patients < 65y (OR 4.91; 95% CI: 3.25 7.43) and Medicaid/CICP patients (OR 4.23; 95% CI: 2.65-7.65) were more likely to have a suboptimal preparation compared to commercial insurance patients. Medicare patients < 65y (OR 5.58; 95% CI: 2.85-10.92) and Medicaid/CICP patients (OR 3.64; CI: 1.60-8.28) were more likely to receive a recommendation for an early repeat colonoscopy compared to commercial insurance patients. Medicare patients < 65y had a significantly higher adjusted ADR (OR 1.50; 95% CI: 1.03-2.18) and adjusted AADR (OR 1.99; 95% CI: 1.15-3.44) compared to commercial insurance patients. CONCLUSIONS: Understanding the reasons for the higher rate of a suboptimal bowel preparation in Medicare < 65y and Medicaid/CICP patients and reducing this rate is critical to improving colonoscopy outcomes and reducing healthcare costs in these populations. PMID- 27187810 TI - [Public health infrastructure investment difficulties in Chile: concessions and public tenders]. AB - This paper seeks to highlight the problems of gaps in health infrastructure in Chile, and to analyze the mechanisms by which it is provided. In Chile this is done in two ways: the first is through competitive bidding or sector-wide modality. The second way is through hospital concessions. Both mechanisms have had difficulties in recent years, which are reported. Finally, we propose ways to improve the provision of health infrastructure in Chile. PMID- 27187822 TI - Genetic variants in ATP6 and ND3 mitochondrial genes are not associated with aggressive prostate cancer in Mexican-Mestizo men with overweight or obesity. AB - Mitochondrial defects have been related to obesity and prostate cancer. We investigated if Mexican-Mestizo men presenting this type of cancer, exhibited somatic mutations of ATP6 and/or ND3.Body mass index (BMI) was determined; the degree of prostate cancer aggressiveness was demarcated by the Gleason score. DNA from tumor tissue and from blood leukocytes was amplified by the polymerase chain reaction and ATP6 and ND3 were sequenced. We included 77 men: 20 had normal BMI, 38 were overweight and 19 had obesity; ages ranged from 52 to 83. After sequencing ATP6 and ND3, from DNA obtained from leukocytes and tumor tissue, we did not find any somatic mutations. All changes observed, in both genes, were polymorphisms. In ATP6 we identified, in six patients, two non-synonymous nucleotide changes and in ND3 we observed that twelve patients presented non synonymous polymorphisms. To our knowledge, this constitutes the first report where the complete sequences of the ATP6 and ND3 have been analyzed in Mexican Mestizo men with prostate cancer and diverse BMI. Our results differ with those reported in Caucasian populations, possibly due to ethnic differences. PMID- 27187821 TI - Leveraging antimicrobial stewardship into improving rates of carbapenem-resistant Enterobacteriaceae. AB - Carbapenem-resistant Enterobacteriaceae (CRE) are among the most critical threats facing our healthcare system and account for significant patient mortality. There is considerable interest in the development of new treatment strategies. However, less attention has been paid to reducing CRE infection rates. Antibiotic stewardship programs can be uniquely empowered to reduce widespread pathogen resistance and by extension, optimize patient care and lower healthcare costs. PMID- 27187824 TI - The Power of Partnerships. PMID- 27187823 TI - Reprogramming of Pancreatic Exocrine Cells AR42J Into Insulin-producing Cells Using mRNAs for Pdx1, Ngn3, and MafA Transcription Factors. AB - Direct reprogramming of pancreatic nonendocrine cells into insulin-producing beta cells represents a promising approach for the treatment of insulin-dependent diabetes. However, its clinical application is limited by the potential for insertional mutagenesis associated with the viral vectors currently used for cell reprogramming. With the aim of developing a nonintegrative reprogramming strategy for derivation of insulin-producing cells, here, we evaluated a new approach utilizing synthetic messenger RNAs encoding reprogramming transcription factors. Administration of synthetic mRNAs encoding three key transcription regulators of beta-cell differentiation-Pdx1, Neurogenin3, and MafA-efficiently reprogrammed the pancreatic exocrine cells into insulin-producing cells. In addition to the insulin genes expression, the synthetic mRNAs also induced the expressions of genes important for proper pancreatic beta-cell function, including Sur1, Kir6.2, Pcsk1, and Pcsk2. Pretreating cells with the chromatin-modifying agent 5-Aza-2' deoxycytidine further enhanced reprogramming efficiency, increasing the proportion of insulin-producing cells from 3.5 +/- 0.9 to 14.3 +/- 1.9% (n = 4). Moreover, 5-Aza-2'-deoxycytidine pretreatment enabled the reprogrammed cells to respond to glucose challenge with increased insulin secretion. In conclusion, our results support that the reprogramming of pancreatic exocrine cells into insulin producing cells, induced by synthetic mRNAs encoding pancreatic transcription factors, represents a promising approach for cell-based diabetes therapy. PMID- 27187825 TI - Multilevel Influences on New Graduate Nurse Transition: A Literature Review. AB - New graduate nurses continue to experience difficulty in transitioning into practice. A literature review was conducted to identify factors that influence new graduate nurse transition. Data from 42 articles were extracted, and significant variables were synthesized from a social ecological perspective. Findings suggest that a complex interplay between intrapersonal, interpersonal, and organizational factors influence transition. A nursing professional development specialist plays a crucial role in implementing educational strategies that address factors across all three levels of influence. PMID- 27187826 TI - Measuring Return on Investment for Professional Development Activities: A Review of the Evidence. AB - In the current complex healthcare environment in which organizations are dealing with reimbursement challenges, nursing professional development practitioners must increasingly demonstrate that the time and resources dedicated to educational activities are worth the impact they have on outcomes. Measuring return on investment guides decisions on resources (people, supplies, time) used for professional development activities by showing the financial impact of such activities. The purpose of this project was to review the literature on return on investment for professional development activities to best guide decision-making for limited resources. This is Part I of two articles, the first of which provides a review of the literature. The second article provides guidance for conducting financial analyses of nursing professional development activities. PMID- 27187827 TI - Partnering to Promote Evidence-Based Practice in a Community Hospital: Implications for Nursing Professional Development Specialists. AB - Nursing professional development specialists working in community hospitals face significant barriers to evidence-based practice that academic medical centers do not. This article describes 7 years of a multifaceted, service academic partnership in a large, urban, community hospital. The partnership has strengthened the nursing professional development role in promoting evidence based practice across the scope of practice and serves as a model for others. PMID- 27187828 TI - Engaging Learners With Social Media. AB - Can social media be used to promote learning? This article includes an overview of social networking sites with specific examples of how nursing professional development practitioners might use each for professional development activities. PMID- 27187829 TI - Improving Efficiency Using a Hybrid Approach: Revising an Intravenous/Blood Workshop in a Clinical Research Environment. AB - Orienting to a new job can be overwhelming, especially if the nurse is required to develop or refine new skills, such as intravenous (IV) therapy or blood administration. At the National Institutes of Health Clinical Center Nursing Department, a group of nurse educators redesigned their IV/Blood Workshop to prepare nurses with skills needed when caring for patients on protocol in a research intensive environment. Innovative teaching strategies and a hybrid instructional approach were used along with a preworkshop activity, skills lab practice, and follow-up skill validation at the unit level to provide a comprehensive curriculum while decreasing resource utilization. PMID- 27187830 TI - Measuring Registered Nurses' Medication Competence in Specialty Settings: An Operating Room Registered Nurse Example. AB - Nursing professional development practitioners play an active, vital role in shaping, implementing, and evaluating competency models in their organizations. This article describes a process for developing and continuously improving knowledge assessment examinations, one component of a competency model. The article defends the use of specialty-specific medication knowledge assessment examinations. The authors recommend future investigations to link nurses' knowledge assessment results to performance in practice and to analyze costs and benefits of knowledge assessment examinations. PMID- 27187831 TI - Nursing Professional Development Specialists of the Future. PMID- 27187833 TI - Steppingstones-Reflecting on Your Professional Career. PMID- 27187832 TI - Future of Interprofessional Simulation Education in the Practice Setting. PMID- 27187834 TI - ANPD's Call to Convention: Pittsburgh, PA, "City of Bridges". PMID- 27187835 TI - Embrace the Change, Seize the Opportunity. PMID- 27187836 TI - Nursing Professional Development: Revision of the Scope and Standards of Practice. PMID- 27187837 TI - An Educational Program to Promote Emotional Mastery Skills in Nurse Managers. AB - A curriculum was designed and implemented for nurse managers to develop and optimize emotional mastery skills. The program is outlined, implementation strategies were discussed, results were measured, and outcomes were reviewed. Outcomes from this program support the value and impact that nursing professional development specialists have on the development of nursing leadership. Nursing professional development specialists will find the curricula useful in addressing emotional mastery skill development in their organizations. PMID- 27187838 TI - Measuring Return on Investment for Professional Development Activities: A Review of the Evidence. PMID- 27187839 TI - Osteosarcoma After Hematopoietic Stem Cell Transplantation in Children and Adolescents: Case Report and Review of the Literature. AB - Osteosarcoma as a secondary malignancy after hematopoietic stem cell transplantation (HSCT) is very rare. We present a case and review of 18 other cases reported to date. Our patient underwent HSCT for myelodysplastic syndrome at the age of 4 years. She developed osteosarcoma 13 years later. She underwent surgery after three courses of neoadjuvant chemotherapy followed by chemotherapy and mifamurtide. She has no evidence of disease 28 months after termination of chemotherapy. In 18 other cases of secondary osteosarcoma in the literature, 15 had received total body irradiation, eight had received alkylating agents, and six had received etoposide. The median interval from HSCT to the onset of osteosarcoma was 6.5 years (range 2.5-15.3), which confirms that children undergoing HSCT should be followed up for many years. In conclusion, osteosarcoma must be included in the differential diagnosis among solid tumors that may develop following HSCT. PMID- 27187840 TI - Self-Catalyzed Growth of Vertically Aligned InN Nanorods by Metal-Organic Vapor Phase Epitaxy. AB - Vertically aligned hexagonal InN nanorods were grown mask-free by conventional metal-organic vapor phase epitaxy without any foreign catalyst. The In droplets on top of the nanorods indicate a self-catalytic vapor-liquid-solid growth mode. A systematic study on important growth parameters has been carried out for the optimization of nanorod morphology. The nanorod N-polarity, induced by high temperature nitridation of the sapphire substrate, is necessary to achieve vertical growth. Hydrogen, usually inapplicable during InN growth due to formation of metallic indium, and silane are needed to enhance the aspect ratio and to reduce parasitic deposition beside the nanorods on the sapphire surface. The results reveal many similarities between InN and GaN nanorod growth showing that the process despite the large difference in growth temperature is similar. Transmission electron microscopy, spatially resolved energy-dispersive X-ray spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and Raman spectroscopy have been performed to analyze the structural properties. Spatially resolved cathodoluminescence investigations are carried out to verify the optical activity of the InN nanorods. The InN nanorods are expected to be the material of choice for high-efficiency hot carrier solar cells. PMID- 27187841 TI - Hemothorax caused by replacement of hemodialysis catheter: A case report. AB - Central venous catheters (CVC) are widely used in clinics to gain vascular access, but the risk and prevalence of catheter-related complications remains a serious issue. We report a long-term dialysis catheter accidentally inserted into the mediastinum via the right jugular vein in a hemodialysis patient. We also review complications associated with vascular catheterization and propose immediate therapeutic interventions for such cases. PMID- 27187842 TI - Nanoparticles decorated with a Schiff's base for the microextraction of Cd, Pb, Ni, and Co in environmental samples. AB - In this paper, we report a new liquid-liquid microextraction procedure called "nanoparticles decorated with a Schiff's base for the microextraction of Cd, Pb, Ni, and Co in environmental samples". The developed procedure was utilized for the extraction of Cd, Pb, Ni, and Co in environmental samples. The Schiff's base was formed by reacting salicylaldehyde with 3-aminopropyltriethoxysilane functionalized iron oxide nanoparticles. Analyte extraction was conducted in a capillary column system loaded with modified nanoparticles and triton X-114 as dispersion medium. 1-Butyl-3-methylimidazolium hexafluorophosphate was employed as an extraction solvent. Acidified methanol in ultrasonic bath was used as desorption solvent, and elemental determination was carried out with flame atomic absorption spectrometer. Characterization of modified nanoparticles was performed with FTIR spectroscopy and transmission electron microscopy. Solution pH, nanoparticles amount, dispersant concentration, ionic liquid, and temperature were optimized for the extraction. Detection limits obtained for Cd, Pb, Ni, and Co were 0.183, 0.201, 0.241, and 0.192 MUg L(-1), respectively, and enhancement factors were 79.1, 86.4, 95.7, and 82.0, respectively. The reproducibility of the developed procedure was in the range of 3.98-5.10%. Validation was checked by applying the developed procedure on certified reference water samples. The microextraction based on nanoparticles decorated with Schiff's base was successfully applied for the extraction of Cd, Pb, Ni, and Co in real environmental water samples. PMID- 27187843 TI - Corrigendum. PMID- 27187844 TI - Quantitative determination of intracellular Asulacrine in MCF-7 breast cancer cells by liquid chromatography-mass spectrometry and its application to cellular pharmacokinetic studies of P188 modified liposomes. AB - Asulacrine (ASL), an analogue of amsacrine, has shown higher anti-breast and anti lung cancer activity. Hereby, a new sensitive and selective liquid chromatography mass spectrometry (LC/MS) method was developed to determine intracellular asulacrine. The chromatographic separation was performed on an Agilent Zorbax Extend-C18 column (2.1 mm i.d. * 50 mm, 5 MUm) using gradient elution with water (2 mmol/L ammonium acetate and 0.1% acetic acid) and acetonitrile as the mobile phase. The detection was achieved with selected ion monitoring mode using electrospray ionization in positive mode with target ions at m/z 465.3 and m/z 326.1 for asulacrine and midazolam, respectively. The standard curve showed a good linearity with the lower limit of quantification of 1 ng/mL, as a result of which, the trace concentration of ASL in cell suspension could be quantified. The intra- and inter-day accuracy ranged from -5.28 to 6.5% and from -6.32 to 1.05%, and the intra- and inter-day precisions were no more than 7.65% and 11.71%, respectively. Additionally, no degradation of asulacrine was observed during stability evaluation. The method was proved to be powerful and practical to determine and compare the intracellular distribution and kinetics of ASL under different formulations in MCF-7 breast cancer cells. PMID- 27187845 TI - Pilot Randomized Study of a Gratitude Journaling Intervention on Heart Rate Variability and Inflammatory Biomarkers in Patients With Stage B Heart Failure. AB - OBJECTIVE: Stage B, asymptomatic heart failure (HF) presents a therapeutic window for attenuating disease progression and development of HF symptoms, and improving quality of life. Gratitude, the practice of appreciating positive life features, is highly related to quality of life, leading to development of promising clinical interventions. However, few gratitude studies have investigated objective measures of physical health; most relied on self-report measures. We conducted a pilot study in Stage B HF patients to examine whether gratitude journaling improved biomarkers related to HF prognosis. METHODS: Patients (n = 70; mean [standard deviation] age = 66.2 [7.6] years) were randomized to an 8 week gratitude journaling intervention or treatment as usual. Baseline (T1) assessments included the six-item Gratitude Questionnaire, resting heart rate variability (HRV), and an inflammatory biomarker index. At T2 (midintervention), the six-item Gratitude Questionnaire was measured. At T3 (postintervention), T1 measures were repeated but also included a gratitude journaling task. RESULTS: The gratitude intervention was associated with improved trait gratitude scores (F = 6.0, p = .017, eta = 0.10), reduced inflammatory biomarker index score over time (F = 9.7, p = .004, eta = 0.21), and increased parasympathetic HRV responses during the gratitude journaling task (F = 4.2, p = .036, eta = 0.15), compared with treatment as usual. However, there were no resting preintervention to postintervention group differences in HRV (p values > .10). CONCLUSIONS: Gratitude journaling may improve biomarkers related to HF morbidity, such as reduced inflammation; large-scale studies with active control conditions are needed to confirm these findings. TRIAL REGISTRATION: Clinicaltrials.govidentifier:NCT01615094. PMID- 27187848 TI - Explicit Facial Emotion Processing in Patients With Dissociative Seizures. AB - OBJECTIVE: There have, as yet, been few experimental studies of explicit facial affect recognition in patients with dissociative seizures (DS). The aim of the study was to examine explicit recognition and physiological responses to facial expressions in this group, relative to healthy controls. METHODS: Forty patients with DS and 43 controls completed a computerized test of facial affect recognition, including five basic expressions (happiness, anger, disgust, fear, neutral). Recognition accuracy, emotional intensity judgements, and skin conductance levels and responses were dependent measures. Analyses controlled for a range of potentially confounding variables, including anxiety, depression, and medication effects. RESULTS: The DS group was less accurate at identifying facial expressions than controls (p = .005, etap = 0.10). No group difference emerged for intensity judgements (p = .72, etap = 0.002). Mean skin conductance levels were higher in the DS group relative to controls (p = .046, etap = 0.053). However, a subgroup of DS patients showed attenuated skin conductance responses to the facial stimuli, compared with controls (p = .015, etap = 0.18). These differences could not be accounted for by possible confounding variables. Recognition accuracy for neutral faces correlated negatively with trauma scores (r = -0.486, p = .002) and abandonment concerns (r = -0.493, p = .002) in the DS group. CONCLUSIONS: Patients with DS showed reduced recognition accuracy for facial affect, despite accurately perceiving its intensity. Elevated autonomic arousal may characterize patients with DS in general, alongside reduced phasic autonomic responses to facial expressions in some patients with the disorder. PMID- 27187846 TI - Associations Among Child Abuse, Depression, and Interleukin-6 in Pregnant Adolescents: Paradoxical Findings. AB - OBJECTIVE: Limited data exist on child abuse-related immune variation during pregnancy, despite implications for maternal and infant health and extensive data showing that abuse history and depression are related to increased inflammation in other populations. This study examined associations among child abuse, depression, circulating levels of inflammatory markers, and perinatal health in pregnant adolescents, a group at high risk for childhood abuse and poor birth outcomes. METHODS: Pregnant teenagers (n = 133; 14-19 years; 89.5% Latina) reported on abuse and depression and had two blood draws (24-27 and 34-37 gestational weeks, second and third trimesters, respectively) for interleukin-6 (IL-6) and C-reactive protein; birth outcomes were collected. RESULTS: Abuse and depression interacted to predict higher IL-6 at second trimester (B = 0.006, p = .011) such that severely abused adolescents with high depression had higher IL-6 relative to severely abused adolescents with low depression; depression did not differentiate IL-6 levels for those with low abuse severity. Abuse and IL-6 also interacted to predict gestational age at birth (B = 0.004, p = .040) such that those with low abuse and high IL-6 and those with high abuse and low IL-6 had infants with earlier gestational age at birth. Cortisol at the second trimester mediated the association between IL-6 and gestational age at birth (indirect effect estimate=-0.143, p < .039). CONCLUSIONS: Depression severity distinguished IL-6 levels among more severely abused pregnant Latina adolescents, but it was unrelated to IL-6 among less severely abused adolescents. Cortisol explained the relationship between IL-6 and earlier gestational age at birth. Multiple adversities and inflammation may influence birth outcomes and potentially affect intergenerational health. PMID- 27187847 TI - Major Depression and Long-Term Survival of Patients With Heart Failure. AB - OBJECTIVES: Previous studies have found that depression predicts all-cause mortality in heart failure (HF), but little is known about its effect on long term survival. This study examined the effects of depression on long-term survival in patients with HF. METHODS: Patients hospitalized with HF (n = 662) at an urban academic medical center were enrolled in a prospective cohort study between January 1994 and July 1999. Depression was assessed on a structured interview during the index hospitalization and on quarterly interviews for 1 year after discharge. Patients were classified at index as having Diagnostic and Statistical Manual, Fourth Edition major depressive disorder (n = 131), minor depression (n = 106), or no depression (n = 425). Clinical data and the National Death Index were used to identify date of death or last known contact through December 19, 2014, up to 20 years after the index hospitalization. The main outcome was time from enrollment to death from any cause. RESULTS: A total of 617 (94.1%) patients died during the follow-up period. Major depressive disorder was associated with higher all-cause mortality compared with no depression (adjusted hazard ratio = 1.64, 95% confidence interval = 1.27-2.11, p = .0001). This association was stronger than that of any of the established predictors of mortality that were included in the fully adjusted model. Patients with persistent or worsening depressive symptoms during the year after discharge were at greatest risk for death. The association between minor depression and survival was not significant. CONCLUSIONS: Major depression is an independent risk factor for all-cause mortality in patients with HF. Its effect persists for many years after the diagnosis of depression. PMID- 27187850 TI - Self-Help for Medically Unexplained Symptoms: A Systematic Review and Meta Analysis. AB - OBJECTIVE: Medically unexplained symptoms (MUS), which are highly prevalent in all fields of medicine, are considered difficult to treat. The primary objective of this systematic review and meta-analysis was to assess the efficacy of self help for adults with MUS. METHODS: Four electronic databases were searched for relevant studies. Randomized controlled trials comparing self-help to usual care or waiting list in adults with MUS were selected. Studies were critically appraised using the Cochrane "risk of bias assessment tool." Standardized mean differences (Hedges g) were pooled using a random-effects model. Outcomes were symptom severity and quality of life (QoL) directly posttreatment and at follow up. RESULTS: Of 582 studies identified, 18 studies met all inclusion criteria. Studies were heterogeneous with regard to patient populations, intervention characteristics, and outcome measures. Compared with usual care or waiting list, self-help was associated with lower symptom severity (17 studies, n = 1894, g = 0.58, 95% confidence interval = 0.32-0.84, p < .001) and higher QoL (16 studies, n = 1504, g = 0.66, 95% confidence interval = 0.34-0.99, p < .001) directly posttreatment. Similar effect sizes were found at follow-up. A high risk of bias was established in most of the included studies. However, sensitivity analyses suggested that this did not significantly influence study results. Funnel plot asymmetry indicated potential publication bias. CONCLUSIONS: Self-help is associated with a significant reduction in symptom severity and improvement of QoL. The methodological quality of included studies was suboptimal, and further research is needed to confirm the findings of this meta-analysis. PMID- 27187849 TI - Cytokine Patterns in Healthy Adolescent Girls: Heterogeneity Captured by Variable and Person-Centered Statistical Strategies. AB - BACKGROUND: Little is known about variation in individual cytokines/cytokine profiles for a large healthy, pediatric population. When cytokines in a healthy group are not abnormally high as in a disease state, it is challenging to determine appropriate statistical strategies. The aims of the study were (1) to describe variation among cytokine concentrations and profiles in healthy adolescent girls, (2) to illustrate utility of data reduction approaches novel to cytokine research, (variable-centered [principal factor analysis, PFA], person centered [latent profile analysis, LPA]), and (3) to demonstrate utility of such methods in linking cytokine profiles to health outcomes (e.g., depressive, anxiety symptoms). METHOD: Serum was analyzed for 13 cytokines representing adaptive and innate immune responses in 262 girls (age = 11, 13, 15, and 17 years). RESULTS: There was great variation in cytokine concentrations. PFA revealed a four-factor solution explaining 73.13% of the shared variance among 13 cytokines (e.g., factor 1 included interleukin [IL]-4, IL-13, IL-5, interferon gamma; 26.65% of the shared variance). The LPA supported classifying girls into subgroups characterized by "high overall" (7.3% of sample), "high adaptive" (26.7%), "high innate" (21%), or "low overall" (45%) cytokine levels. Factors and profiles were useful in describing individual differences in depressive/anxiety symptoms (e.g., factor 1 positively associated with depressive symptoms but negatively with trait anxiety; increased depressive symptoms or trait anxiety was associated with greater likelihood of being in the "high adaptive" group). CONCLUSIONS: Healthy girls showed differences in cytokine levels and patterns of variation and important associations with psychological variables. PFA and LPA offer novel approaches useful for examining cytokine panels in healthy populations. PMID- 27187851 TI - A Stepwise Psychotherapy Intervention for Reducing Risk in Coronary Artery Disease (SPIRR-CAD): Results of an Observer-Blinded, Multicenter, Randomized Trial in Depressed Patients With Coronary Artery Disease. AB - BACKGROUND: Depression predicts adverse prognosis in patients with coronary artery disease (CAD), but previous treatment trials yielded mixed results. We tested the hypothesis that stepwise psychotherapy improves depressive symptoms more than simple information. METHODS: In a multicenter trial, we randomized 570 CAD patients scoring higher than 7 on the Hospital Anxiety and Depression Scale depression subscale to usual care plus either one information session (UC-IS) or stepwise psychotherapy (UC-PT). UC-PT patients received three individual psychotherapy sessions. Those still depressed were offered group psychotherapy (25 sessions). The primary outcome was changed in the Hospital Anxiety and Depression Scale-depression scores from baseline to 18 months. Preplanned subgroup analyses examined whether treatment responses differed by patients' sex and personality factors (Type D). RESULTS: The mean (standard deviation) depression scores declined from 10.4 (2.5) to 8.7 (4.1) at 18 months in UC-PT and from 10.4 (2.5) to 8.9 (3.9) in UC-IS (both p < .001). There was no significant group difference in change of depressive symptoms (group-by-time effect, p = .90). Preplanned subgroup analyses revealed no differences in treatment effects between men versus women (ptreatment-by-sex interaction = .799) but a significant treatment-by-Type D interaction on change in depressive symptoms (p = .026) with a trend for stronger improvement with UC-PT than UC-IS in Type D patients (n = 341, p = .057) and no such difference in improvement in patients without Type D (n = 227, p = .54). CONCLUSIONS: Stepwise psychotherapy failed to improve depressive symptoms in CAD patients more than UC-IS. The intervention might be beneficial for depressed CAD patients with Type D personality. However, this finding requires further study. TRIAL REGISTRATION: www.clinicaltrials.gov NCT00705965; www.isrctn.com ISRCTN76240576. PMID- 27187852 TI - Macrophage Superoxide Anion Production in Essential Hypertension: Associations With Biological and Psychological Cardiovascular Risk Factors. AB - OBJECTIVE: Essential hypertension is an important risk factor for coronary artery disease and its underlying process atherosclerosis, but involved mechanisms are not fully understood. Both macrophages and superoxide anions have been proposed to play a major role in the pathogenesis of atherosclerosis. In the present study, we investigated whether macrophages of individuals with hypertension show higher nicotinamide adenine dinucleotide phosphate oxidase-derived superoxide anion production compared with normotensive individuals. Furthermore, we examined associations between macrophage superoxide anion production and the psychological factors depression and chronic stress independent from hypertension status. METHODS: We studied 30 hypertensive (mean [standard deviation] = 48.7 [2.4] years) and 30 age-matched normotensive men (mean [standard deviation] = 48.6 [2.4] years). We assessed macrophage superoxide anion production using the WST-1 assay. The assay is based on the chemical reduction of the cell-impermeative tetrazolium salt WST-1 by superoxide anions that are produced by activated human ex vivo isolated monocyte-derived macrophages. We further evaluated whether chronic stress or depressive symptom severity was associated with macrophage superoxide anion production. All analyses were adjusted for potential confounders. RESULTS: Individuals with hypertension showed higher superoxide anion production compared with normotensive individuals (F(1,58) = 11.56, p = .001). Complementary analyses using mean arterial blood pressure as a continuous measure revealed that higher mean arterial pressure correlated significantly with higher WST-1 reduction (beta = .38, p = .003, DeltaR = .145). These results remained significant when controlling for potential confounding influences. Chronic stress was related to higher WST-1 reduction scores, but this association was not statistically significant (beta = .24, p = .067, DeltaR = .053); depression levels were not significantly associated with WST-1 reduction scores (p = .24). CONCLUSIONS: Our results indicate higher macrophage superoxide anion production in individuals with hypertension compared with normotensive individuals. This may suggest a mechanism underlying cardiovascular risk with hypertension. PMID- 27187853 TI - Income and Markers of Immunological Cellular Aging. AB - OBJECTIVE: Socioeconomic disadvantage may contribute to poor health through immune-related biological mechanisms. We examined the associations between socioeconomic status, as measured by annual household income, and T-cell markers of aging, including the ratios of CD4 and CD8 effector cells to naive cells (E/N ratio) and the CD4/CD8 T-cell ratio. We hypothesized that participants with a lower income would have higher E/N ratios and lower CD4/CD8 ratios compared with participants with a higher income, and that these associations would be partially mediated by elevated cytomegalovirus (CMV) IgG antibody levels, a virus implicated in aging and clonal expansion of T cells. METHODS: Data were from 79 individuals who participated in the population-based Detroit Neighborhood Health Study. We used linear regression to quantify the association between a $10,000 decrease in income and each ratio outcome. RESULTS: After adjustment for age, sex, race, smoking, medication use, and lifetime history of mental health conditions, lower income was associated with a 0.41 (95% confidence interval = 0.09-0.72) log-unit increase in the CD4 E/N ratio and a 0.20 (95% confidence interval = 0.02-0.39) log-unit increase in the CD8 E/N ratio. CMV immunoglobulin G antibody level partially mediated these associations. CONCLUSIONS: Our study suggests that low socioeconomic status is associated with immunological aging as measured by the E/N ratio and that impaired immune control of CMV may partially mediate these associations. PMID- 27187856 TI - Design, synthesis and biological evaluation of novel EGFR/HER2 dual inhibitors bearing a oxazolo[4,5-g]quinazolin-2(1H)-one scaffold. AB - For the purpose of developing novel EGFR/HER2 tyrosine kinases inhibitors with high inhibition activity and low toxicity, two novel series of oxazolo[4,5 g]quinazolin-2(1H)-one derivatives as EGFR/HER2 dual inhibitors introducing two electrophiles 2-(2-bromoacetyl)ethyl and 2-(2-chloroacetoxy)ethyl group as side chain at 1-position respectively and evaluated their EGFR and HER2 inhibition activity and toxicity comparing with Lapatinib. All these compounds were evaluated by EGFR and HER2 kinase inhibition and two anti-proliferation assays in vitro. Most of the designed compounds exhibited moderate to high inhibition activity against EGFR and HER2. Especially, compounds 11o, 11p, 12e and 12f presented high inhibition against EGFR and HER2. Furthermore, compounds 11p and 12f also had well exhibition to excellent anti-proliferation activity against human lung adenocarcinoma cell line (A549) and human breast cancer cell line (SK Br3), and 12f also exhibited the lowest toxicity against human embryonic lung fibroblast cell line (HELF) cell. Finally, compound 12f presented remarkably higher inhibition efficacy towards tumour growth than Lapatinib in a mouse lewis lung cancer (LLC) xenograft model. PMID- 27187855 TI - Synthesis of novel diterpenoid analogs with in-vivo antitumor activity. AB - A lead compound 7 has antitumor effect, which was discovered by screening our small synthetic natural product-like compound (NPL) library. Based on the lead compound, a series of novel tricyclic diterpene analogs were synthesized and investigated for their activity against the growth of various tumor cell lines using the sulforhodamine B (SRB) assay. To our delight, most aromatic amide compounds exhibited more potent antitumor activity than the lead compound. The most active compound 19 (QW30) showed an average IC50 0.33 MUM, which was 15-fold more potent than the lead compound. Most of the compounds with potent antitumor activity displayed less toxic on normal human fibroblasts (HAF) in comparison with the tumor cell lines. Especially 19, its selectivity indexes (SI) between HAF and cancer cell lines was 17.3 times better than the positive control compound podophyllotoxin. The apoptosis, colony formation and transwell migration assays of 7 and 19 were performed on T47D cell line. The in-vivo antitumor effect of 19 was also observed in T47D tumor-bearing mice without obvious toxicity. PMID- 27187854 TI - Patient Health Questionnaire Anxiety and Depression Scale: Initial Validation in Three Clinical Trials. AB - OBJECTIVE: We examine the reliability and validity of the Patient Health Questionnaire Anxiety and Depression Scale (PHQ-ADS)-which combines the nine-item Patient Health Questionnaire depression scale and seven-item Generalized Anxiety Disorder scale-as a composite measure of depression and anxiety. METHODS: Baseline data from 896 patients enrolled in two primary-care based trials of chronic pain and one oncology-practice-based trial of depression and pain were analyzed. The internal reliability, standard error of measurement, and convergent, construct, and factor structure validity, as well as sensitivity to change of the PHQ-ADS were examined. RESULTS: The PHQ-ADS demonstrated high internal reliability (Cronbach alpha values of .8 to .9) in all three trials. PHQ ADS scores can range from 0 to 48 (with higher scores indicating more severe depression/anxiety), and the estimated standard error of measurement was approximately 3 to 4 points. The PHQ-ADS showed strong convergent (most correlations, 0.7-0.8 range) and construct (most correlations, 0.4-0.6 range) validity when examining its association with other mental health, quality of life, and disability measures. PHQ-ADS cutpoints of 10, 20, and 30 indicated mild, moderate, and severe levels of depression/anxiety, respectively. Bifactor analysis showed sufficient unidimensionality of the PHQ-ADS score. PHQ-ADS change scores at 3 months differentiated (p < .0001) between individuals classified as worse, stable, or improved by a reference measure, providing preliminary evidence for sensitivity to change. CONCLUSIONS: The PHQ-ADS may be a reliable and valid composite measure of depression and anxiety which, if validated in other populations, could be useful as a single measure for jointly assessing two of the most common psychological conditions in clinical practice and research. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00926588 (SCOPE); NCT00386243 (ESCAPE); NCT00313573 (INCPAD). PMID- 27187857 TI - Synthesis and biological evaluation of 4-(2-fluorophenoxy)-3,3'-bipyridine derivatives as potential c-met inhibitors. AB - Six series of novel 4-(2-fluorophenoxy)-3,3'-bipyridine derivatives conjugated with aza-aryl formamide/amine scaffords were designed and synthesized through a structure-based molecular hybridization approach. The target compounds were evaluated for c-Met kinase inhibitory activities and cytotoxicity against four cancer cell lines (HT-29, A549, MKN-45 and MDA-MB-231) in vitro. Most compounds exhibited moderate to excellent potency, and the most promising candidate 26c (c Met kinase IC50 = 8.2 nM) showed a 4.7-fold increase in cytotoxicity against c Met-addicted MKN-45 cell line in vitro (IC50 = 3 nM), superior to that of Foretinib (IC50 = 23 nM). The preliminary structure-activity relationship indicated that a 1H-benzo [e] [1,3,4]thiadiazine-3-carboxamide-4,4-dioxide moiety as linker contributed to the antitumor potency. PMID- 27187858 TI - Anticancer properties of new synthetic hybrid molecules combining naphtho[2,3 b]furan-4,9-dione or benzo[f]indole-4,9-dione motif with phosphonate subunit. AB - In this paper we report an efficient and general synthesis of substituted 3 diethoxyphosphorylnaphtho [2,3-b]furan-4,9-diones and 3-diethoxyphosphorylbenzo [f]indole-4,9-diones which integrate the natural 1,4-naphtalenedione scaffold, present in several anticancer agents with the phosphonate moiety. The cytotoxicity of such hybrid molecules was tested against two leukemia cell lines, HL-60 and NALM-6 and against a breast adenocarcinoma MCF-7 cell line. Selected compounds were also tested on normal human cells: HUVEC and MCF-10A. In general, naphthofuran-4,9-diones showed much higher cytotoxic activity (IC50 values below 10 MUM) than benzoindole-4,9-diones. The most promising 2-(2-chlorophenyl)-3 diethoxyphosphorylnaphtho [2,3-b]furan-4,9-dione, with the highest cytotoxic activity in the MTT test, was chosen for further evaluation of its anticancer potential. This compound, tested on HL-60 and MCF-7 cells inhibited cell proliferation, generated DNA damage and induced apoptosis. The suggested mechanism of its cytotoxic activity was the generation of intracellular reactive oxygen species and the induction of mitochondrial membrane potential dissipation. PMID- 27187859 TI - Novel spirothiazamenthane inhibitors of the influenza A M2 proton channel. AB - The development of treatments for influenza that inhibit the M2 proton channel without being susceptible to the widespread resistance mechanisms associated with the adamantanes is an ongoing challenge. Using a yeast high-throughput yeast growth restoration assay designed to identify M2 channel inhibitors, a single screening hit was uncovered. This compound (3), whose structure was incorrectly identified in the literature, is an inhibitor with similar potency to amantadine against WT M2. A library of derivatives of 3 was prepared and activity against WT M2 and the two principal mutant strains (V27A and S31N) was assessed in the yeast assay. The best compounds were further evaluated in an antiviral plaque reduction assay using engineered WT, V27A and S31N M2 influenza A strains with otherwise identical genetic background. Compound 63 was found to inhibit all three virus strains in this cell based antiviral assay at micromolar concentrations, possibly through a mechanism other than M2 inhibition. PMID- 27187861 TI - Total synthesis and in vitro bioevaluation of clavaminols A, C, H & deacetyl clavaminol H as potential chemotherapeutic and antibiofilm agents. AB - A highly concise and expedient total synthesis of bioactive clavaminols (1-4) has been executed using commercially available achiral compound decanol. The synthetic strategy relied on trans-Wittig olefination, Sharpless asymmetric epoxidation, regioselective azidolysis and in situ detosylation followed by reduction as key reactions with good overall yield. Based on biological evaluation studies of all the synthesized compounds, it was observed that the clavaminol A (1) exhibited good cytotoxicity against DU145 and SKOV3 cell lines with IC50 value of 10.8 and 12.5 MUM, respectively. Clavaminol A (1) and deacetyl clavaminol H (3) displayed selective promising inhibition towards Gram-positive pathogenic bacterial strains and showed good antifungal activity against the tested Candida strains. In addition, compounds 1 and 3 have demonstrated significant bactericidal activity. Compound 3 was found to be equipotent to the standard drug Miconazole displaying MFC value of 15.6 MUg/mL against Candida albicans MTCC 854, C. albicans MTCC 1637, C. albicans MTCC 3958 and Candida glabrata MTCC 3019. Compounds 1 and 3 were also able to inhibit the biofilm formation of Micrococcus luteus MTCC 2470 and Staphylococcus aureus MLS16 MTCC 2940. Clavaminol A (1) increased the levels of reactive oxygen species (ROS) accumulation in M. luteus MTCC 2470. PMID- 27187860 TI - Structural modifications at the 6-position of thieno[2,3-d]pyrimidines and their effects on potency at FLT3 for treatment of acute myeloid leukemia. AB - Fms-like tyrosine kinase 3 (FLT3) is a well-known and important target for the treatment of acute myeloid leukemia (AML). A series of thieno[2,3-d]pyrimidine derivatives from a modification at the 6-position were synthesized to identify effective FLT3 inhibitors. Although compounds 1 and 2 emerged as promising FLT3 inhibitors among the synthesized compounds, both compounds exhibited poor metabolic stability in human and rat liver microsomes. Hence, further optimization was required for the discovery of FLT3 inhibitors, with a focus on improving metabolic stability. Compound 16d, which had structural modifications of the methyl group at the 5-position and the 4-(2-methylaminoethoxy) phenyl group at the 6-position, exhibited good inhibitory activity against FLT3 and showed effective antiproliferative activity against four leukemia cell lines, including MV4-11. Moreover, compound 16d displayed enhanced metabolic stability. The results of this study indicated that 16d could be a promising compound for further optimization and development as a potent FLT3 inhibitor. PMID- 27187862 TI - Aroylhydrazone iron chelators: Tuning antioxidant and antiproliferative properties by hydrazide modifications. AB - Aroylhydrazones such as salicylaldehyde isonicotinoyl hydrazone (SIH) are tridentate iron chelators that may possess antioxidant and/or antineoplastic activities. Their main drawback, their low stability in plasma, has recently been partially overcome by exchanging the aldimine hydrogen for an unbranched alkyl group. In this study, ten analogs of methyl- and ethyl-substituted SIH derivatives with modified hydrazide scaffolds were synthesized to further explore their structure-activity relationships. Their iron-chelation efficiencies, anti- or pro-oxidant potentials, abilities to induce protection against model oxidative injury on the H9c2 cell line derived from rat embryonic cardiac tissue, cytotoxicities on the same H9c2 cells and antiproliferative activities on MCF-7 human breast adenocarcinoma and HL-60 human promyelotic leukemia cell lines were evaluated. Compounds derived from lipophilic naphthyl and biphenyl hydrazides displayed highly selective antiproliferative activities against both MCF-7 and HL 60 cell lines, and they showed markedly improved stabilities in plasma compared to SIH. Of particular interest is a hydrazone prepared from 2 hydroxypropiophenone and pyridazin-4-carbohydrazide that showed a considerable antiproliferative effect and protected cardiomyoblasts against oxidative stress with a five-fold higher selectivity compared to the parent compound SIH. Thus, this work highlighted new structure-activity relationships among antiproliferative and antioxidant aroylhydrazones and identified new lead compounds for further development. PMID- 27187863 TI - Conjugation of weak ligands with weak antigens to activate TLR-7: A step toward better vaccine adjuvants. AB - To study the structure-activity relationship (SAR) of Toll-like receptor 7 (TLR 7) agonists based on 8-oxoadenines, a novel subset of C9-substituted 8-hydroxy-2 (2-methoxyethoxy)-adenines and their antigen conjugates were synthesized. In vitro, the ability of cytokines (IL-12p70 and IFN-gamma) induction of ligands with alkyl acid at C9-position were very weak compared with benzoic acid counter parts. Unexpectedly, its antigen conjugates that conjugated with proteins or peptides with weak immunogenicity, showed enhanced activity of cytokines induction. After administered systemically in mice in vivo, all conjugates induced prolonged increase in pro-inflammatory cytokines and antigen-specific IgG levels in serum compared with free compounds. Results from molecular dynamics (MD) simulations further confirmed the conclusion and provided the details of interaction to explain the phenomenon of experiment. In conclusion, we discovered that TLR-7 could be activated via some conjugates of weak ligand and weak antigen, which could be safer adjuvant candidates for vaccines in the future. PMID- 27187864 TI - Combretastatin A-4 analogues with benzoxazolone scaffold: Synthesis, structure and biological activity. AB - In order to design and synthesize a new class of heterocyclic analogues of natural combretastatin A-4 and its synthetic derivative AVE8062, the benzoxazolone ring was selected as a scaffold for a bioisosteric replacement of the ring B of both molecules. A library of 28 cis- and trans-styrylbenzoxazolones was obtained by a modified Wittig reaction under Boden's conditions. Structures of the newly synthesized compounds bearing the 3,4,5-trimethoxy-, 3,4-dimethoxy-, 3,5-dimethoxy-, and 4-methoxystyryl fragment at position 4, 5, 6 or 7 of benzoxazolone core were determined on the basis of spectral and X ray data. The in vitro cytotoxicity of styrylbenzoxazolones against different cell lines was examined. Stilbene derivative 16Z, (Z)-3-methyl-6-(3,4,5-trimethoxystyryl)-2(3H) benzoxazolone, showed highest antiproliferative potential of the series, with IC50 of 0.25 MUM against combretastatin resistant cell line HT-29, 0.19 MUM against HepG2, 0.28 MUM against EA.hy926 and 0.73 MUM against K562 cells. Furthermore, the results of flow cytometric analysis confirmed that 16Z induced cell cycle arrest in G2/M phase in the cell lines like combretastatin A-4. This arrest is followed by an abnormal exit of cells from mitosis without cytokinesis into a pseudo G1-like multinucleate state leading to late apoptosis and cell death. Accordingly, synthetic analogue 16Z was identified as the most promising potential anticancer agent in present study, and was selected as lead compound for further detailed investigations. PMID- 27187865 TI - N'-((2-(6-bromo-2-oxo-2H-chromen-3-yl)-1H-indol-3-yl)methylene)benzohydrazide as a probable Bcl-2/Bcl-xL inhibitor with apoptotic and anti-metastatic potential. AB - A wide number of marketed drugs and drug candidates in cancer clinical development contain halogen substituents. The aim of the present study was to synthesize a series of halogen incorporated indole-coumarin hybrid schiff bases - N'-((2-(2-oxo-2H-chromen-3-yl)-1H-indol-3-yl)methylene)benzohydrazides and to investigate their apoptotic and anti-migratory potential in human breast adenocarcinoma cells as well as to examine their Bcl-2 and Bcl-xL protein binding ability via in silico docking. Hybrid 5g with a bromine atom in position-7 of coumarin ring displayed significant dose dependent cytotoxic activity with high selectivity to MCF-7 cells in MTT assay. Cell cycle progression analysis of 5g treated cells using flow cytometer exhibited a cell cycle arrest in the S phase and accumulation of cells in the subG1 phase. The apoptotic mode of cell death induced by 5g was further confirmed by Annexin-V staining assay. The wound healing assay revealed a profound impairment in the migration of MCF-7 cells presumably due to down-regulation of Bcl-2 and Bcl-xL proteins induced by 5g as observed in immunoblotting analysis. SAR studies of these hybrid molecules based on cell viability and docking were also probed. The most active pharmacophore 5g was found to bind favourably to Bcl-2 and Bcl-xL in docking simulation analysis suggesting it to be a probable small molecule Bcl-2/Bcl-xL inhibitor and a potential lead for breast cancer chemotherapy with apoptotic and anti-metastatic properties. PMID- 27187867 TI - Nontraumatic Subclavian Artery Abnormalities: Spectrum of MDCT Findings. AB - OBJECTIVE: The subclavian arteries (SCAs) may exhibit a wide spectrum of nontraumatic pathologic conditions ranging from common diseases, such as atherosclerosis, to vascular emergencies that are associated with a high morbidity and high mortality, such as type A aortic dissection and acute arterial thrombosis. MDCT angiography is an excellent modality to diagnose pathologic conditions of the SCAs. CONCLUSION: Optimization of CT acquisition protocols and interactive interpretation with 2D multiplanar reformatting and 3D rendering techniques are critical for diagnostic accuracy. PMID- 27187866 TI - Design, synthesis, anticoagulant activity evaluation and molecular docking studies of a class of N-ethyl dabigatran derivatives. AB - A class of N-ethyl dabigatran derivatives was designed based on pharmacological strategies for inhibition of thrombin activity and the structure-activity relationship studies of the previous dabigatran derivatives. Activities of these novel compounds were predicted based on CoMFA model, and most of the compounds had comparable predicted activity with dabigatran. All of screened compounds were synthesized and characterized by (1)H NMR, (13)C NMR and HRMS. Subsequently, these compounds were evaluated inhibitory activity on thrombin. Among these compounds, 9a-9e, 9h, 9l-9n and 9p exhibited comparable inhibitory activity to dabigatran (IC50 = 1.20 nM), additionally, compound 9p (IC50 = 0.96 nM) exhibited better inhibitory activity than dabigatran. Moreover, compound 9p also exhibited a fairly good inhibitory activity for arteriovenous thrombosis with inhibition rate of (85.35 +/- 0.72) %, which was comparable to that of dabigatran (85.07 +/- 0.61) %. These results, along with related molecular docking studies, could provide an important basis for further development of compound 9p as a potent thrombin inhibitor. PMID- 27187868 TI - High-Efficiency Iron Photosensitizer Explained with Quantum Wavepacket Dynamics. AB - Fe(II) complexes have long been assumed unsuitable as photosensitizers because of their low-lying nonemissive metal centered (MC) states, which inhibit electron transfer. Herein, we describe the excited-state relaxation of a novel Fe(II) complex that incorporates N-heterocyclic carbene ligands designed to destabilize the MC states. Using first-principles quantum nuclear wavepacket simulations we achieve a detailed understanding of the photoexcited decay mechanism, demonstrating that it is dominated by an ultrafast intersystem crossing from (1)MLCT-(3)MLCT proceeded by slower kinetics associated with the conversion into the (3)MC states. The slowest component of the (3)MLCT decay, important in the context of photosensitizers, is much longer than related Fe(II) complexes because the population transfer to the (3)MC states occurs in a region of the potential where the energy gap between the (3)MLCT and (3)MC states is large, making the population transfer inefficient. PMID- 27187869 TI - Silicon-Carbon Bond Formation via Nickel-Catalyzed Cross-Coupling of Silicon Nucleophiles with Unactivated Secondary and Tertiary Alkyl Electrophiles. AB - A wide array of cross-coupling methods for the formation of C-C bonds from unactivated alkyl electrophiles have been described in recent years. In contrast, progress in the development of methods for the construction of C-heteroatom bonds has lagged; for example, there have been no reports of metal-catalyzed cross couplings of unactivated secondary or tertiary alkyl halides with silicon nucleophiles to form C-Si bonds. In this study, we address this challenge, establishing that a simple, commercially available nickel catalyst (NiBr2.diglyme) can achieve couplings of alkyl bromides with nucleophilic silicon reagents under unusually mild conditions (e.g., -20 degrees C); especially noteworthy is our ability to employ unactivated tertiary alkyl halides as electrophilic coupling partners, which is still relatively uncommon in the field of cross-coupling chemistry. Stereochemical, relative reactivity, and radical trap studies are consistent with a homolytic pathway for C-X bond cleavage. PMID- 27187870 TI - Persistent Lung Disease in Adults with NKX2.1 Mutation and Familial Neuroendocrine Cell Hyperplasia of Infancy. AB - RATIONALE: Neuroendocrine cell hyperplasia of infancy (NEHI) is a diffuse lung disease that presents in infancy and improves during childhood. Long-term outcomes have not previously been described. In one familial cohort, we have reported that NEHI is associated with a heterozygous variant of NKX2.1/TTF1. OBJECTIVES: Our objective was to determine whether pulmonary abnormalities persist in adults with NEHI, to aid in elucidating the natural history of this disease. METHODS: Four adult relatives with heterozygous NKX2.1 mutation and with clinical histories compatible with NEHI enrolled in a prospective study that included questionnaires, pulmonary function tests, and chest computed tomography scans. MEASUREMENTS AND MAIN RESULTS: Mild radiologic abnormalities including mosaicism were seen in all four cases. Three individuals had obstruction on pulmonary function tests, two had marked air trapping, and three had symptomatic impairments with exercise intolerance. CONCLUSIONS: Although clinical improvement occurs over time, NEHI may result in lifelong pulmonary abnormalities in some cases. Further studies are required to better describe the natural history of this disease and would be facilitated by additional delineation of genetic mechanisms to enable improved case identification. PMID- 27187873 TI - Meta-cognitive online sequential extreme learning machine for imbalanced and concept-drifting data classification. AB - In this paper, a meta-cognitive online sequential extreme learning machine (MOS ELM) is proposed for class imbalance and concept drift learning. In MOS-ELM, meta cognition is used to self-regulate the learning by selecting suitable learning strategies for class imbalance and concept drift problems. MOS-ELM is the first sequential learning method to alleviate the imbalance problem for both binary class and multi-class data streams with concept drift. In MOS-ELM, a new adaptive window approach is proposed for concept drift learning. A single output update equation is also proposed which unifies various application specific OS-ELM methods. The performance of MOS-ELM is evaluated under different conditions and compared with methods each specific to some of the conditions. On most of the datasets in comparison, MOS-ELM outperforms the competing methods. PMID- 27187871 TI - Thiolactomycin-Based Inhibitors of Bacterial beta-Ketoacyl-ACP Synthases with in Vivo Activity. AB - beta-Ketoacyl-ACP synthases (KAS) are key enzymes involved in the type II bacterial fatty acid biosynthesis (FASII) pathway and are putative targets for antibacterial discovery. Several natural product KAS inhibitors have previously been reported, including thiolactomycin (TLM), which is produced by Nocardia spp. Here we describe the synthesis and characterization of optically pure 5R thiolactomycin (TLM) analogues that show improved whole cell activity against bacterial strains including methicillin-resistant Staphylococcus aureus (MRSA) and priority pathogens such as Francisella tularensis and Burkholderia pseudomallei. In addition, we identify TLM analogues with in vivo efficacy against MRSA and Klebsiella pneumoniae in animal models of infection. PMID- 27187872 TI - Outcomes of intra-detrusor injections of botulinum toxin in patients with spina bifida: A systematic review. AB - CONTEXT: Bladder management in spina bifida patients relies on clean intermittent catheterization and oral antimuscarinics with a significant failure rate. The efficacy of intradetrusor injections of botulinum toxin has been confirmed in patients with spinal cord injury or multiple sclerosis but not in patients with myelomeningocele. OBJECTIVE: To conduct a systematic review of current evidence regarding the efficacy of intra-detrusor injections of Botulinum Toxin A (BTX-A) in spina bifida patients with neurogenic detrusor overactivity (NDO) refractory to antimuscarinics. METHODS: A research has been conducted on Medline and Embase using the keywords: ("spina bifida" OR "myelomeningocele" OR "dysraphism") AND "toxin." The search strategy and studies selection were performed using the PICOS method according to the PRISMA statement. RESULT: Twelve published series were included (n = 293 patients). All patients were <18 years old. There was no randomized study comparing BTX-A versus placebo and most studies had no control group. Most studies reported a clinical and urodynamic improvement with resolution of incontinence in 32-100% of patients, a decrease in maximum detrusor pressure from 32 to 54%, an increase of maximum cystometric capacity from 27 to 162%, and an improvement in bladder compliance of 28-176%. Two studies suggested lower efficacy in patients with low compliance bladder compared to those with isolated detrusor overactivity. CONCLUSION: Intradetrusor injections of BTX-A could be effective in children with spina bifida but this assumption is not supported by high level of evidence studies. There is no data available in adult patients. Neurourol. Urodynam. 36:557-564, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27187875 TI - Pulmonary implications in inflammatory bowel disease: not a rare event. PMID- 27187874 TI - Chemically Modulated Carbon Nitride Nanosheets for Highly Selective Electrochemiluminescent Detection of Multiple Metal-ions. AB - Chemical structures of two-dimensional (2D) nanosheet can effectively control the properties thus guiding their applications. Herein, we demonstrate that carbon nitride nanosheets (CNNS) with tunable chemical structures can be obtained by exfoliating facile accessible bulk carbon nitride (CN) of different polymerization degree. Interestingly, the electrochemiluminescence (ECL) properties of as-prepared CNNS were significantly modulated. As a result, unusual changes for different CNNS in quenching of ECL because of inner filter effect/electron transfer and enhancement of ECL owing to catalytic effect were observed by adding different metal ions. On the basis of this, by using various CNNS, highly selective ECL sensors for rapid detecting multiple metal-ions such as Cu(2+), Ni(2+), and Cd(2+) were successfully developed without any labeling and masking reagents. Multiple competitive mechanisms were further revealed to account for such enhanced selectivity in the proposed ECL sensors. The strategy of preparing CNNS with tunable chemical structures that facilely modulated the optical properties would open a vista to explore 2D carbon-rich materials for developing a wide range of applications such as sensors with enhanced performances. PMID- 27187877 TI - [Key Issue "Granulomatous Uveitis - Sarcoidosis"]. PMID- 27187878 TI - [Imaging and Laboratory Diagnostics for Tuberculosis]. AB - Diagnosis of tuberculosis (TB) is difficult, since symptoms are often very unspecific or lacking. However active, prompt and accurate diagnosis is the key element in the public health response to tuberculosis and the cornerstone of tuberculosis control. Different diagnostic methods for an assured diagnosis of TB are necessary. Chest radiography is a useful keystone to identify tuberculosis, but diagnosis of tuberculosis cannot be established by radiography alone. CT scanning is used in patients without pathological chest radiography but clinically suspected active TB and to differentiate TB from other diseases. Radiological appearance is primarily determined by the immune status of patients and caverns and disseminated disease foci are often observed. Laboratory diagnostic methods include microscopic identification of acid-fast mycobacteria from any body fluid (especially sputum), as well as isolation and characterisation of mycobacteria in culture. It is then possible to type the pathogens by the shape of their colony, their growth behavior and their biochemical characteristics. These methods are regarded as the gold standard in diagnosis of active TB. In patients who are highly suspected of having TB, but whose sputum specimens tested negative for mycobacteria, a nucleic acid amplification test is additionally performed. Moreover, sensitivity testing with first and second line antitubercular drugs is applied as standard. Laboratory diagnostic testing of cellular immunity against pathogenic mycobacteria employs the tuberculin skin test (TST, Mantoux tuberculin test) or the more specific interferon gamma test to determine gamma interferon released by T lymphocytes stimulated in vitro. The new ELISA and ELISPOT procedures exhibit higher test specificity and less cross reactivity to NTM (non-tuberculosis mycobacteria), are independent of BCG-vaccination status and correlate better with the degree of exposure than does the TST. PMID- 27187880 TI - [Efficacy of a Dexamethasone Implant for the Treatment of Refractory Cystoid Macular Oedema in Non-Infectious Uveitis]. AB - PURPOSE: To evaluate the efficacy of an intravitreal dexamethasone implant (Ozurdex(r)) in patients with cystoid macular oedema (CME) suffering from non infectious uveitis. METHODS: Monocentric, retrospective, single-arm analysis in 49 patients (59 implanted eyes) with inactive uveitis, in whom CME had been unresponsive to corticosteroids and/or immunosuppressants and systemic acetazolamide, and who received a dexamethasone implant. Patients were followed up at 6, 12 and 24 weeks after unilateral (n = 39)/bilateral (n = 10) implantation. The primary outcome measure was central foveal thickness (CFT), as measured by Spectralis optical coherence tomography (OCT); secondary outcome measures were improvement in best-corrected visual acuity (BCVA), laser flare photometry and safety measures, including intraocular pressure (IOP) and cataract progression. RESULTS: At 6, 12 and 24 weeks, mean CFT was reduced (>= 20 %) in 68, 44 and 45 % and BCVA improved (>= 2 lines) in 47, 40 and 26 %, respectively, as compared to baseline. At 6, 12 and 24 weeks, significant flare reduction was observed in 70, 41, and 42 %, respectively. Cumulative cataract progression was observed in 12, 18 and 31 % at 6, 12 and 24 weeks, respectively. IOP >= 22 mmHg was noted in 5 % at baseline and in 21, 3, and 0 % at 6, 12 and 24 weeks, respectively. CONCLUSIONS: In uveitis patients with CME refractory to systemic anti-inflammatory drugs, the dexamethasone implant improves CME transiently. However, IOP increase and cataract progression are common side effects. PMID- 27187879 TI - [Ocular Manifestations in Sarcoidosis]. AB - Sarcoidosis is an inflammatory multi-organ disease of unknown pathogenesis, characterised by non-necrotising granulomata. Sarcoidosis predominantly manifests in the lung, but any other organ may be affected. Ocular involvement is present in about 25 to 50 % of patients. The most common ocular manifestation is uveitis, especially of the anterior eye segment. If ocular sarcoidosis is suspected, interdisciplinary assessment of the patient is mandatory, including laboratory tests, chest X-ray, assessment by a specialist in internal medicine and, ideally, histological evidence of granuloma formation in a tissue specimen. Other (infectious) causes of granulomatous inflammation need to be excluded, especially tuberculosis or syphilis. For the ophthalmological assessment, detection of granulomatous lesions is of particular importance, especially by visualising chorioretinal granuloma by fluorescein and indocyanin green angiography. Cystoid macular oedema and glaucoma are the most frequent complications limiting visual acuity. Corticosteroids, which can be administered either locally or systemically, are the mainstay of therapy. Depending on the clinical course and the development of ocular complications, systemic steroid-sparing immunosuppressive medication may be indicated. PMID- 27187881 TI - [Postoperative Follow-Up of Glaucoma Drainage Devices]. AB - There is an increasing trend towards using glaucoma drainage implants. The postoperative management of such devices depends on their technical characteristics and specific complications. The Baerveldt glaucoma implant with its larger surface area has been shown to lower mean intraocular pressure more effectively than the Ahmed-FP7 implant. As a non-valve implant, however, it has been associated with a higher rate of severe complications, particularly ocular hypotension. Moreover, glaucoma implants may induce diplopia if they interfere with extraocular muscles. Topical treatment with antibiotics and steroids is necessary in cases of intraocular inflammation. In refractory cases, the tube may even have to be removed. Surgical reposition of the tube may be indicated when it is severely dislocated. Increased intraocular pressure is primarily treated by pressure-lowering medications during postoperative follow-up. If topical glaucoma medication is insufficient to control increases in intraocular pressure due to encapsulation, a second implant may be considered or the capsule surrounding the implant may be excised to reduce outflow resistance or additional cyclodestructive procedures can be performed. Chronic hypotension may be treated with tube ligation or occlusion. Severe corneal oedema may require lamellar keratoplasty. Conjunctival erosions with tube exposure or tube retractions also require surgical correction. PMID- 27187882 TI - [New Possibilities in Retinal Diagnostics Using OCT Angiography]. AB - BACKGROUND: Instruments for using OCT angiography (OCTA) in daily clinical practice have recently become available. The aim of this paper is to report the possibilities, advantages and limitations of OCTA in the clinical diagnosis of diseases of the posterior segment of the eye. PATIENTS/METHODS: Patients with diabetic retinopathy, retinal vascular occlusions, and age-related macular degeneration who had been assigned to fluorescein angiography (FA) additionally underwent an AngioPlexTM-OCTA examination, which captures a 6 * 6 mm scanning area centred on the fovea. If deemed necessary, 3 * 3 mm volume scans were created in regions of interest. The findings of FA and OCTA were correlated and compared. RESULTS: The OCTA procedure took only a few seconds, was easily integrated into the standard OCT diagnostic imaging procedure, and delivered highly detailed, three dimensional images of the entire microvasculature of the retina and choroid. Microvascular changes, such as microaneurysms, intraretinal microvascular abnormalities, non-perfused areas, alterations in the foveal avascular zone (FAZ) and neovascularization were reliably detected. Overall, OCTA results were in good agreement with the results of the FA. Additionally, OCTA provided more detailed and three dimensional information and thus permitted a better assessment of the spatial extension of microvascular abnormalities. Due to OCTA's limited scanning area, vascular alterations in the mid-periphery were detected only if their location had already been determined by FA. Although OCTA does not show leakage, macular oedema can be diagnosed from OCTA, together with OCT thickness measurements. CONCLUSION: OCTA provides important three dimensional information on vascular alterations and is already an indispensable diagnostic method. As the procedure takes just a few seconds and can be performed non invasively, OCTA is well suited as a monitoring method and may allow early diagnosis. In this sense, prospective studies are required to determine precise OCTA analytical strategies for specific diseases. It is very likely that OCTA will revolutionise the diagnosis of retinal and choroidal diseases; however, it is not yet clear estimated to what extent it will replace FA. PMID- 27187883 TI - [Therapeutic Options in Vitreomacular Traction With or Without a Macular Hole]. AB - Treatment is usually indicated for symptomatic vitreomacular traction (VMT) with or without a full thickness macular hole (FTMH) and without spontaneous resolution. Ultrastructural parameters are evaluated by SD-OCT, in order to classify the vitreoretinal interface and to estimate the success rate of treatment. The resolution rate after therapy with intravitreal Jetrea(r) (Ocriplasmin) is high (up to 70 %) in patients with symptomatic focal vitreomacular traction (<= 1500 um) with or without a macular hole (<= 250 um) and with no epiretinal membrane (ERM), but depends on the exact baseline analysis. All other patients with idiopathic traction retinopathy should be treated by minimal invasive pars plana vitrectomy (MIVI). Vitreoretinal surgery effectively removes traction and gives a high closure rate of a full thickness macular hole (FTMH, 90 to 100 %). It is now a very safe procedure with few side effects. Despite a low risk profile (cataract, retinal tear etc.) the indication for surgery needs to take the safety profile into account. Therefore vitrectomy is only indicated in symptomatic patients complaining of blurred vision, VA reduction and metamorphopsia. Vitrectomy is also indicated in patients whose treatment by pharmacologic vitreolysis has failed. PMID- 27187884 TI - [Evaluation of Field of Vision in Private Accident Insurance]. AB - A simple new scheme to evaluate defects in field of vision in private accident insurance. PMID- 27187885 TI - [Clinical Results After Implantation of a New Diffractive, Multifokal Intraocular Lens with a Reduced Near Add Power (+ 2.75 D)]. AB - PURPOSE: Evaluation of the clinical data 3 months after implantation of a new diffractive multifocal intraocular lens (MIOL) with a reduced near add power of + 2.75 D. METHODS: In a prospective study, patients who underwent cataract surgery or refractive lens exchange with implantation of an MIOL (Tecnis ZKB00, Abbott Medical Optics, Santa Ana, California, USA) were included. Three months postoperative corrected and uncorrected visual acuities at different distances were measured and evaluated. Those patients that underwent bilateral MIOL implantation additionally filled out a questionnaire 3 months postoperatively. RESULTS: Between October 2013 and August 2014, 115 eyes of 62 patients were implanted with the ZKB00 IOL. Mean postoperative refractions were - 0.27 +/- 0.44 D for the spherical equivalent, respectively. Mean binocular CDVA was - 0.01 +/- 0.3 logMAR with a mean binocular UDVA of 0.06 +/- 0.08 logMAR. For near distance in 40 cm, an UNVA of 0.07 +/- 0.10 logMAR three months postoperatively was measured. CONCLUSION: The ZKB00 IOL belongs to a group of novel MIOL with an increased intermediate visual performance. Our study shows good visual acuity at all distances, as well as a high rate of satisfaction and subjectively good image quality. PMID- 27187886 TI - [Rare Conjunctival Metastasis in Cancer of Unknown Primary Syndrome]. PMID- 27187887 TI - [Seasonal and Perennial Allergic Rhinoconjunctivitis]. PMID- 27187888 TI - Cardiac Index Declines During Long-Term Left Ventricular Device Support. AB - To investigate longitudinal trends in valvular and ventricular function with long term left ventricular assist device (LVAD) therapy, we analyzed hemodynamic and echocardiographic data of patients with at least 2 years of continuous LVAD support. All 130 patients who underwent HeartMate II implantation at our institution between 2005 and 2012 were reviewed. Twenty patients had hemodynamic and echocardiographic evaluations in both the early (0-6 months) and late (2-3 years) postoperative period. Patients on inotropic therapy or temporary mechanical support were excluded. The average times of early and late hemodynamic evaluations were 59 +/- 41 days and 889 +/- 160 days, respectively. Cardiac index (CI) declined by an average of 0.4 L/min/m2 (P = 0.04) with concomitant increase in pulmonary capillary wedge pressure (PCWP; P = 0.02). The right atrial pressure to PCWP (RAP:PCWP) ratio decreased during LVAD support suggesting improvement in right ventricular function. While there was an increase in degree of aortic insufficiency (AI) at the late follow-up period (P = 0.008), dichotomization by median decline in CI (-0.4 L/min/m2 ) indicated no difference in prevalence of AI among the groups. CI declined in patients with HeartMate II after 2 years of continuous support. An increase in preload and afterload was observed in those with the greatest decline in CI. PMID- 27187890 TI - From the Editor-in-Chief's Desk. PMID- 27187891 TI - Bremsstrahlung enhancement in electron probe microanalysis for homogeneous samples using Monte Carlo simulation. AB - Fluorescence enhancement in samples irradiated in a scanning electron microscope or an electron microprobe should be appropriately assessed in order not to distort quantitative analyses. Several models have been proposed to take into account this effect and current quantification routines are based on them, many of which have been developed under the assumption that bremsstrahlung fluorescence correction is negligible when compared to characteristic enhancement; however, no concluding arguments have been provided in order to support this assumption. As detectors are unable to discriminate primary from secondary characteristic X-rays, Monte Carlo simulation of radiation transport becomes a determinant tool in the study of this fluorescence enhancement. In this work, bremsstrahlung fluorescence enhancement in electron probe microanalysis has been studied by using the interaction forcing routine offered by penelope 2008 as a variance reduction alternative. The developed software allowed us to show that bremsstrahlung and characteristic fluorescence corrections are in fact comparable in the studied cases. As an extra result, the interaction forcing approach appears as a most efficient method, not only in the computation of the continuum enhancement but also for the assessment of the characteristic fluorescence correction. PMID- 27187889 TI - Dietary Intake among Adolescents in a Middle-Income Country: An Outcome from the Malaysian Health and Adolescents Longitudinal Research Team Study (the MyHeARTs Study). AB - Optimal nutrition is essential for healthy growth during adolescence. This study aims to investigate the baseline nutritional intake of Malaysian adolescents by gender, body mass index, and places of residence, both urban and rural. A cohort study was conducted consisting of 794 adolescents (aged 13-years) attending 15 public secondary schools from the Central (Kuala Lumpur and Selangor) and Northern (Perak) Regions of Peninsular Malaysia. Qualified dietitians conducted a 7-day historical assessment of habitual food intakes. Facilitated by flipcharts and household measurement tools, detailed information on portion sizes and meal contents were recorded. Nutritionist ProTM Diet Analysis software was also used to analyze the dietary records.The mean age of the adolescents was 12.86 +/- 0.33 y; the mean energy intake was 1659.0 +/- 329.6 kcal/d. Males had significantly (P < .001) higher energy intake than females (1774.0 +/- 369.8 vs 1595.2 +/- 320.6 kcal/d); adolescents in rural schools consumed more energy and cholesterol (P < .001) compared to adolescents in urban schools (1706.1 +/- 377.7 kcal/d and 244.1 +/- 100.2 mg/d, respectively). Obese adolescents in rural schools consumed more energy and sugar (1987.6 +/- 374.0 kcal/d and 48.9 +/- 23.0 g/d) (p-value <0.001).The dietary intake of normal weight versus obese adolescents differs by the location of their school. Thus, the implementation of a structured and tailored intervention is recommended to help minimize this nutritional inequality. PMID- 27187892 TI - Discerning different and opposite effects of hydrogenase on the corrosion of mild steel in the presence of phosphate species. PMID- 27187893 TI - Does cannabis use moderate smoking cessation outcomes in treatment-seeking tobacco smokers? Analysis from a large multi-center trial. AB - BACKGROUND AND OBJECTIVE: Tobacco and cannabis are frequently used in combination and cannabis co-use may lead to poor tobacco cessation outcomes. Therefore, it is important to explore if cannabis co-use is associated with a reduced likelihood of achieving successful tobacco abstinence among treatment-seeking tobacco smokers. The present study examined whether current cannabis use moderated tobacco cessation outcomes after 12 weeks of pharmacological treatment (varenicline vs. nicotine patch vs. placebo) with adjunctive behavioral counseling. METHODS: Treatment-seeking tobacco smokers (N = 1,246) were enrolled in an intent-to-treat study, of which 220 were current cannabis users. Individuals were randomly assigned to 12 weeks of placebo (placebo pill plus placebo patch), nicotine patch (active patch plus placebo pill), or varenicline (active pill plus placebo patch), plus behavioral counseling. The primary endpoint was biochemically verified 7-day point prevalence abstinence at the end of treatment. RESULTS: Controlling for rate of nicotine metabolism, treatment arm, age, sex, alcohol, and level of nicotine dependence, cannabis users were as successful at achieving biochemically verified 7-day point prevalence abstinence compared to tobacco-only smokers. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Findings suggest that cannabis use does not hinder the ability to quit tobacco smoking. Future tobacco cessation studies should employ prospective, longitudinal designs investigating cannabis co-use over time and at different severity levels. (Am J Addict 2016;25:291-296). PMID- 27187894 TI - Pharmacokinetics of once-daily darunavir/ritonavir in HIV-1-infected pregnant women. AB - OBJECTIVES: HIV antiretroviral therapy during pregnancy is recommended to reduce the risk of mother-to-child transmission and for maternal care. Physiological changes during pregnancy can affect pharmacokinetics. The impact of pregnancy was evaluated for once-daily (qd) darunavir/ritonavir. METHODS: HIV-1-infected pregnant women on an antiretroviral regimen that includes darunavir were enrolled in the study and further treated with darunavir/ritonavir 800/100 mg qd. Plasma concentrations were assessed over 24 h during the second and third trimesters and postpartum using a validated high-performance liquid chromatography tandem mass spectrometry assay for total darunavir and ritonavir, and using (14) C-darunavir fortified plasma for unbound darunavir. Pharmacokinetic parameters were derived using noncompartmental analysis. Safety and antiviral response were assessed at all visits. RESULTS: Data were available for 16 women. The area under the plasma concentration-time curve from 0 to 24 h (AUC24h ) for total darunavir was 34-35% lower during pregnancy vs. postpartum. Unbound darunavir AUC24h was 20-24% lower during pregnancy vs. postpartum. The minimum plasma concentration of total and unbound darunavir was 32-50% and 13-38% lower, respectively, during pregnancy vs. postpartum. The antiviral response (< 50 HIV-1 RNA copies/mL) was 59% at baseline and increased to 87-100% during the trial; the CD4 count increased over time. One serious adverse event (gestational diabetes) was judged as possibly related to study medication. All 16 infants born to women remaining in the study at delivery were HIV-1 negative (two were premature). CONCLUSIONS: Total darunavir exposure decreased during pregnancy, but the decrease was less for unbound (active) darunavir. These changes are not considered clinically relevant. Darunavir/ritonavir 800/100 mg qd may therefore be a treatment option for HIV-1 infected pregnant women. PMID- 27187895 TI - Cost comparison of radiofrequency catheter ablation versus cryoablation for atrial fibrillation in hospitals using both technologies. AB - OBJECTIVE: The objective of this study was to compare the cost of radiofrequency (RF) ablation vs cryoablation (Cryo) for atrial fibrillation (AF). METHODS: This retrospective cohort study used 2013-2014 records from the Premier Healthcare Database for adults with AF catheter ablation. Exclusions included non-AF ablation, surgical ablation, valve replacement or repair, or cardiac implant. Hospitals were required to perform >=20 procedures using each technology, with the technology identifiable in at least 90% of cases. The primary endpoint was total variable visit cost, modeled separately for inpatient and outpatient visits, and adjusted for patient and hospital characteristics. Technology was categorized as RF or Cryo, with dual-technology procedures classified as Cryo. The Cryo cohort was further divided into Cryo only and Cryo with RF for sensitivity analyses. A composite adverse event endpoint was also compared. RESULTS: A total of 1261 RF procedures and 1276 Cryo procedures, of which 500 also used RF, met study criteria. RF patients were slightly older and sicker, and had more cardiovascular disease and additional arrhythmias. Adjusted inpatient costs were $2803 (30.0%) higher for Cryo, and adjusted outpatient costs were $2215 (19.5%) higher. Sensitivity models showed higher costs in both Cryo sub groups compared with RF. Procedural complication rates were not significantly different between cohorts (p-values: 0.4888 inpatient, 0.5072 outpatient). CONCLUSION: AF ablation using RF results in significantly lower costs compared with Cryo, despite an RF population with more cardiovascular disease. This saving cannot be attributed to a difference in complication rates. PMID- 27187896 TI - Correspondence: Reply to 'On the nature of strong piezoelectricity in graphene on SiO2'. PMID- 27187897 TI - Solvent Dynamics in Solutions of PNIPAM in Water/Methanol Mixtures-A Quasi Elastic Neutron Scattering Study. AB - The solvent dynamics of concentrated solutions of poly(N-isopropylacrylamide) (PNIPAM, 25 wt %) in water/methanol mixtures (85:15 v/v) are measured with the aim of shedding light onto the cononsolvency effect. Quasi-elastic neutron scattering (QENS) with contrast variation has been carried out at temperatures below and above the cloud point by using in the first set of experiments the mixture H2O:d-MeOD (d-MeOD denotes fully deuterated methanol) as a solvent and in the second set of experiments the mixture D2O:MeOH (MeOH denotes methanol). As a reference, bulk H2O, bulk MeOH and the mixtures H2O:d-MeOD and D2O:MeOH (both 85:15 v/v) have been investigated as well. In the PNIPAM solution in H2O:d-MeOD, two water populations are identified, namely strongly and less strongly arrested water. At the cloud point, the former is partially released from PNIPAM. The diffusion coefficient of the latter one is similar to the one in the water/methanol mixture, and its residence time decreases at the cloud point. The PNIPAM solution in D2O:MeOH reveals similar dynamics to the one in H2O:d-MeOD which may reflect that the dynamics of MeOH near the PNIPAM chain is similar to the one of H2O. The similarity may, however, partially be due to H/D exchange between D2O and MeOH. In both PNIPAM solutions, the mean-square displacement of the PNIPAM chain decreases gradually above the cloud point. PMID- 27187898 TI - Stellate Ganglion Block for the Treatment of Posttraumatic Stress Disorder: A Randomized, Double-Blind, Controlled Trial. AB - OBJECTIVE: In this study, we aimed to determine if stellate ganglion block (SGB) could reduce symptoms of posttraumatic stress disorder (PTSD) in comparison with sham therapy in military service members. METHODS: In a randomized trial in which both participants and assessors were blind, participants with PTSD received either an SGB or a sham procedure. Posttraumatic stress disorder symptoms were measured using the CAPS (Clinician-Administered PTSD Scale) and self-report measures of PTSD, depression, anxiety, and pain. Subjects underwent assessment before the procedure and at 1 week, 1 month, and 3 months after the procedure. Patients receiving sham injections were allowed to cross over to the treatment group, and participants who maintained criteria for PTSD were allowed to receive a second SGB treatment. RESULTS: Posttraumatic stress disorder, anxiety, and depression scores all showed improvement across time, but there was no statistically or clinically relevant difference in outcomes between the active and control groups. Individuals who crossed over from sham treatment to SGB similarly showed no greater improvement with the SGB treatment. Improvement in CAPS was greater with a second SGB treatment than after the first treatment. CONCLUSIONS: Although previous case series have suggested that SGB offers an effective intervention for PTSD, this study did not demonstrate any appreciable difference between SGB and sham treatment on psychological or pain outcomes. Future studies should examine if differences in treatment methods or patient population could allow individuals with PTSD to benefit from SGB, but current evidence does not support widespread or indiscriminant clinical use of the procedure for PTSD. PMID- 27187906 TI - Stop stunting: improving child feeding, women's nutrition and household sanitation in South Asia. AB - The latest available data indicate that 38% of South Asia's children aged 0-59 months are stunted. Such high prevalence combined with the region's large child population explain why South Asia bears about 40% of the global burden of stunting. Recent analyses indicate that the poor diets of children in the first years of life, the poor nutrition of women before and during pregnancy and the prevailing poor sanitation practices in households and communities are important drivers of stunting, most likely because of underlying conditions of women's status, food insecurity, poverty, and social inequalities. With this evidence in mind, UNICEF Regional Office for South Asia convened the Regional Conference: Stop Stunting: Improving Child Feeding, Women's Nutrition, and Household Sanitation in South Asia (New Delhi, November 10-12, 2014). The Conference provided a knowledge-for-action platform with three objectives: (1) share state of-the-art research findings on the causes of child stunting and its consequences for child growth and development and the sustainable growth and development of nations; (2) discuss better practices and the cost and benefits of scaling up programmes to improve child feeding, women's nutrition, and household sanitation in South Asia; and (3) identify implications for sectoral and cross-sectoral policy, programme, advocacy and research to accelerate progress in reducing child stunting in South Asia. This overview paper summarizes the rationale for the focus on improving child feeding, women's nutrition, and household sanitation as priority areas for investment to prevent child stunting in South Asia. It builds on the invited papers presented at or developed as a follow on to the Stop Stunting Conference. PMID- 27187908 TI - Reducing stunting by improving maternal, infant and young child nutrition in regions such as South Asia: evidence, challenges and opportunities. AB - Meeting the high nutrient needs of pregnant and lactating women and their young children in regions such as South Asia is challenging because diets are dominated by staple foods with low nutrient density and poor mineral bioavailability. Gaps in nutritional adequacy in such populations probably date back to the agricultural revolution ~10 000 years ago. Options for improving diets during the first 1000 days include dietary diversification and increased intake of nutrient rich foods, improved complementary feeding practices, micronutrient supplements and fortified foods or products specifically designed for these target groups. Evidence from intervention trials indicates that several of these strategies, both prenatal and post-natal, can have a positive impact on child growth, but results are mixed and a growth response is not always observed. Nutrition interventions, by themselves, may not result in the desired impact if the target population suffers from frequent infection, both clinical and subclinical. Further research is needed to understand the mechanisms underlying both prenatal and post-natal growth restriction. In the meantime, implementation and rigorous evaluation of integrated interventions that address the multiple causes of stunting is a high priority. These intervention packages should ideally include improved nutrition during both pregnancy and the post-natal period, prevention and control of prenatal and post-natal infection and subclinical conditions that restrict growth, care for women and children and stimulation of early child development. In regions such as South Asia, such strategies hold great promise for reducing stunting and enhancing human capital formation. PMID- 27187907 TI - Childhood stunting: a global perspective. AB - Childhood stunting is the best overall indicator of children's well-being and an accurate reflection of social inequalities. Stunting is the most prevalent form of child malnutrition with an estimated 161 million children worldwide in 2013 falling below -2 SD from the length-for-age/height-for-age World Health Organization Child Growth Standards median. Many more millions suffer from some degree of growth faltering as the entire length-for-age/height-for-age z-score distribution is shifted to the left indicating that all children, and not only those falling below a specific cutoff, are affected. Despite global consensus on how to define and measure it, stunting often goes unrecognized in communities where short stature is the norm as linear growth is not routinely assessed in primary health care settings and it is difficult to visually recognize it. Growth faltering often begins in utero and continues for at least the first 2 years of post-natal life. Linear growth failure serves as a marker of multiple pathological disorders associated with increased morbidity and mortality, loss of physical growth potential, reduced neurodevelopmental and cognitive function and an elevated risk of chronic disease in adulthood. The severe irreversible physical and neurocognitive damage that accompanies stunted growth poses a major threat to human development. Increased awareness of stunting's magnitude and devastating consequences has resulted in its being identified as a major global health priority and the focus of international attention at the highest levels with global targets set for 2025 and beyond. The challenge is to prevent linear growth failure while keeping child overweight and obesity at bay. PMID- 27187909 TI - Improving women's nutrition imperative for rapid reduction of childhood stunting in South Asia: coupling of nutrition specific interventions with nutrition sensitive measures essential. AB - The implications of direct nutrition interventions on women's nutrition, birth outcome and stunting rates in children in South Asia are indisputable and well documented. In the last decade, a number of studies present evidence of the role of non-nutritional factors impacting on women's nutrition, birth outcome, caring practices and nutritional status of children. The implications of various dimensions of women's empowerment and gender inequality on child stunting is being increasingly recognised. Evidence reveals the crucial role of early age of marriage and conception, poor secondary education, domestic violence, inadequate decision-making power, poor control over resources, strenuous agriculture activities, and increasing employment of women and of interventions such as cash transfer scheme and microfinance programme on undernutrition in children. Analysis of the nutrition situation of women and children in South Asia and programme findings emphasise the significance of reaching women during adolescence, pre-conception and pregnancy stage. Ensuring women enter pregnancy with adequate height and weight and free from being anemic is crucial. Combining nutrition-specific interventions with measures for empowerment of women is essential. Improvement in dietary intake and health services of women, prevention of early age marriage and conception, completion of secondary education, enhancement in purchasing power of women, reduction of work drudgery and elimination of domestic violence deserve special attention. A range of programme platforms dealing with health, education and empowerment of women could be strategically used for effectively reaching women prior to and during pregnancy to accelerate reduction in stunting rates in children in South Asia. PMID- 27187911 TI - Determinants of stunting and poor linear growth in children under 2 years of age in India: an in-depth analysis of Maharashtra's comprehensive nutrition survey. AB - We use a representative sample of 2561 children 0-23 months old to identify the factors most significantly associated with child stunting in the state of Maharashtra, India. We find that 22.7% of children were stunted, with one-third (7.4%) of the stunted children severely stunted. Multivariate regression analyses indicate that children born with low birthweight had a 2.5-fold higher odds of being stunted [odds ratio (OR) 2.49; 95% confidence interval (CI) 1.96-3.27]; children 6-23 months old who were not fed a minimum number of times/day had a 63% higher odds of being stunted (OR 1.63; 95% CI 1.24-2.14); and lower consumption of eggs was associated with a two-fold increased odds of stunting in children 6 23 months old (OR 2.07; 95% CI 1.19-3.61); children whose mother's height was < 145 cm, had two-fold higher odds of being stunted (OR 2.04; 95% CI 1.46-2.81); lastly, children of households without access to improved sanitation had 88% higher odds of being severely stunted (OR 1.88; 95% CI 1.17-3.02). Attained linear growth (height-for-age z-score) was significantly lower in children from households without access to improved sanitation, children of mothers without access to electronic media, without decision making power regarding food or whose height was < 145 cm, children born with a low birthweight and children 6-23 months old who were not fed dairy products, fruits and vegetables. In Maharashtra children's birthweight and feeding practices, women's nutrition and status and household sanitation and poverty are the most significant predictors of stunting and poor linear growth in children under 2 years. Key messages One in five (22.7%) of children 0-23 months old in the state of Maharashtra were stunted, and one-third (7.4%) of the stunted children were severely stunted. Birthweight, child feeding, women's nutrition and household sanitation were the most significant predictors of stunting and poor linear growth in children under 2 years. Children born to mothers whose height was below 145 cm, had two-fold higher odds of being stunted; children born with a low birthweight had a 2.5-fold higher odds of being stunted. Low feeding frequency and low consumption of eggs, dairy products, fruits and vegetables were associated with stunting and poor linear growth in children 6-23 months old. Children of households without access to improved sanitation had 88% higher odds of being severely stunted. PMID- 27187910 TI - Can water, sanitation and hygiene help eliminate stunting? Current evidence and policy implications. AB - Stunting is a complex and enduring challenge with far-reaching consequences for those affected and society as a whole. To accelerate progress in eliminating stunting, broader efforts are needed that reach beyond the nutrition sector to tackle the underlying determinants of undernutrition. There is growing interest in how water, sanitation and hygiene (WASH) interventions might support strategies to reduce stunting in high-burden settings, such as South Asia and sub Saharan Africa. This review article considers two broad questions: (1) can WASH interventions make a significant contribution to reducing the global prevalence of childhood stunting, and (2) how can WASH interventions be delivered to optimize their effect on stunting and accelerate progress? The evidence reviewed suggests that poor WASH conditions have a significant detrimental effect on child growth and development resulting from sustained exposure to enteric pathogens but also due to wider social and economic mechanisms. Realizing the potential of WASH to reduce stunting requires a redoubling of efforts to achieve universal access to these services as envisaged under the Sustainable Development Goals. It may also require new or modified WASH strategies that go beyond the scope of traditional interventions to specifically address exposure pathways in the first 2 years of life when the process of stunting is concentrated. PMID- 27187912 TI - Achieving behaviour change at scale: Alive & Thrive's infant and young child feeding programme in Bangladesh. AB - The Alive & Thrive programme scaled up infant and young child feeding interventions in Bangladesh from 2010 to 2014. In all, 8.5 million mothers benefited. Approaches - including improved counselling by frontline health workers during home visits; community mobilization; mass media campaigns reaching mothers, fathers and opinion leaders; and policy advocacy - led to rapid and significant improvements in key practices related to breastfeeding and complementary feeding. (Evaluation results are forthcoming.) Intervention design was based on extensive formative research and behaviour change theory and principles and was tailored to the local context. The programme focused on small, achievable actions for key audience segments identified through rigorous testing. Promotion strategies took into account underlying behavioural determinants and reached a high per cent of the priority groups through repeated contacts. Community volunteers received monetary incentives for mothers in their areas who practised recommended behaviours. Programme monitoring, midterm surveys and additional small studies to answer questions led to ongoing adjustments. Scale-up was achieved through streamlining of tools and strategies, government branding, phased expansion through BRAC - a local non-governmental implementing partner with an extensive community-based platform - and nationwide mainstreaming through multiple non-governmental organization and government programmes. Key messages Well-designed and well-implemented large-scale interventions that combine interpersonal counselling, community mobilization, advocacy, mass communication and strategic use of data have great potential to improve IYCF practices rapidly. Formative research and ongoing studies are essential to tailor strategies to the local context and to the perspectives of mothers, family members, influential community members and policymakers. Continued use of data to adjust programme elements is also central to the process. Scale-up can be facilitated through strategic selection of partners with existing community-based platforms and through mass media, where a high proportion of the target audience can be reached through communication channels such as broadcast media. Sustaining the impacts will involve commitments from government and capacity building. The next step for capacity building would involve understanding barriers and constraints and then coming up with appropriate strategies to address them. One of the limitations we experienced was rapid transition of staff in key positions of implementing agencies, in government leadership, donors and other stakeholders. There was a need for continued advocacy, orientation and teaching related to strategic programme design, behaviour change, effective implementation and use of data. PMID- 27187914 TI - Estimating the cost of delivering direct nutrition interventions at scale: national and subnational level insights from India. AB - India's national nutrition and health programmes are largely designed to provide evidence-based nutrition-specific interventions, but intervention coverage is low due to a combination of implementation challenges, capacity and financing gaps. Global cost estimates for nutrition are available but national and subnational costs are not. We estimated national and subnational costs of delivering recommended nutrition-specific interventions using the Scaling Up Nutrition (SUN) costing approach. We compared costs of delivering the SUN interventions at 100% scale with those of nationally recommended interventions. Target populations (TP) for interventions were estimated using national population and nutrition data. Unit costs (UC) were derived from programmatic data. The cost of delivering an intervention at 100% coverage was calculated as (UC*projected TP). Cost estimates varied; estimates for SUN interventions were lower than estimates for nationally recommended interventions because of differences in choice of intervention, target group or unit cost. US$5.9bn/year are required to deliver a set of nationally recommended nutrition interventions at scale in India, while US$4.2bn are required for the SUN interventions. Cash transfers (49%) and food supplements (40%) contribute most to costs of nationally recommended interventions, while food supplements to prevent and treat malnutrition contribute most to the SUN costs. We conclude that although such costing is useful to generate broad estimates, there is an urgent need for further costing studies on the true unit costs of the delivery of nutrition-specific interventions in different local contexts to be able to project accurate national and subnational budgets for nutrition in India. PMID- 27187913 TI - Evidence-based evolution of an integrated nutrition-focused agriculture approach to address the underlying determinants of stunting. AB - Despite progress in reducing hunger and malnutrition since the 1990s, many still suffer from undernutrition and food insecurity, particularly women and young children, resulting in preterm birth, low birthweight and stunting, among other conditions. Helen Keller International (HKI) has addressed malnutrition and household food insecurity through implementation of an Enhanced Homestead Food Production (EHFP) programme that increases year-round availability and intake of diverse micronutrient-rich foods and promotes optimal nutrition and hygiene practices among poor households. This paper reviews the evolution and impact of HKI's EHFP programme and identifies core components of the model that address the underlying determinants of stunting. To date, evaluations of EHFP have shown impact on food production, consumption by women and children and household food security. Sale of surplus produce has increased household income, and the use of a transformative gender approach has empowered women. EHFP has also realized nutrition improvements in many project sites. Results from a randomized control trial (RCT) in Baitadi district, Nepal showed a significant improvement in a range of practices known to impact child growth, although no impact on stunting. Additional non-RCT evaluations in Kailali district of Nepal, demonstrated a 10.5% reduction in stunting and in the Chittagong Hill Tracts in Bangladesh, revealed an 18% decrease in stunting. Based on evidence, the EHFP has evolved into an integrated package that includes agriculture, nutrition, water/hygiene/sanitation, linkages to health care, women's empowerment, income generation and advocacy. Closing the stunting gap requires long-term exposure to targeted multi-sectoral solutions and rigorous evaluation to optimize impact. PMID- 27187915 TI - The costs of stunting in South Asia and the benefits of public investments in nutrition. AB - South Asia is home to the largest number of stunted children worldwide: 65 million or 37% of all South Asian children under 5 were stunted in 2014. The costs to society as a result of stunting during childhood are high and include increased mortality, increased morbidity (in childhood and later as adults), decreased cognitive ability, poor educational outcomes, lost earnings and losses to national economic productivity. Conversely, investing in nutrition provides many benefits for poverty reduction and economic growth. This article draws from analyses conducted in four sub-Saharan countries to demonstrate that investments in nutrition can also be very cost-effective in South Asian countries. Specifically, the analyses demonstrate that scaling up a set of 10 critical nutrition-specific interventions is highly cost-effective when considered as a package. Most of the interventions are also very cost-effective when considered individually. By modelling cost-effectiveness of different scale-up scenarios, the analysis offers insights into ways in which the impact of investing in nutrition interventions can be maximized under budget constraints. Rigorous estimations of the costs and benefits of nutrition investments, similar to those reported here for sub-Saharan countries, are an important next step for all South Asian countries in order to drive political commitment and action and to enhance allocative efficiency of nutrition resources. PMID- 27187916 TI - Understanding the null-to-small association between increased macroeconomic growth and reducing child undernutrition in India: role of development expenditures and poverty alleviation. AB - Empirical evidence suggests that macroeconomic growth in India is not correlated with any substantial reductions in the prevalence of child undernutrition over time. This study investigates the two commonly hypothesized pathways through which macroeconomic growth is expected to reduce child undernutrition: (1) an increase in public developmental expenditure and (2) a reduction in aggregate income-poverty levels. For the anthropometric data on children, we draw on the data from two cross-sectional waves of National Family Health Survey conducted in 1992-1993 and 2005-2006, while the data for per capita net state domestic product and per capita public spending on developmental expenditure and headcount ratio of poverty were obtained from the Reserve Bank of India and the Government of India expert committee reports. We find that between 1992-1993 and 2005-2006, state-level macroeconomic growth was not associated with any substantial increases in public development expenditure or substantial reductions in poverty at the aggregate level. Furthermore, the association between changes in public development expenditure or aggregate poverty and changes in undernutrition was small. In summary, it appears that the inability of macroeconomic growth to translate into reductions in child undernutrition in India is likely a consequence of the macroeconomic growth not translating into substantial investments in development expenditure that could matter for children's nutritional status and neither did it substantially improve incomes of the poor, a group where undernutrition is also the highest. The findings here build a case to advocate a 'support-led' strategy for reducing undernutrition rather than simply relying on a 'growth-mediated' strategy. Key messages Increases in macroeconomic growth have not been accompanied by substantial increases in public developmental spending or reduction in aggregate poverty headcount ratio in India. Association between increases in public development expenditure or poverty headcount ratios and changes in child undernutrition, in particular, child stunting, is small to null. Reducing the burden of undernutrition in India cannot be accomplished solely relying on a growth-mediated strategy, and a concerted support-led strategy is required. PMID- 27187917 TI - Drivers of nutritional change in four South Asian countries: a dynamic observational analysis. AB - This paper quantifies the factors explaining long-term improvements in child height for age z-scores in Bangladesh (1996/1997-2011), India (1992/1993 2005/2006), Nepal (1997-2011) and Pakistan (1991-2013). We apply the same statistical techniques to data from a common data source from which we have extracted a set of common explanatory variables that capture 'nutrition sensitive' factors. Three are particularly important in explaining height for age z-score changes over these timeframes: improvements in material well-being; increases in female education; and improvements in sanitation. These factors have comparable associations across all four countries. PMID- 27187919 TI - Stop stunting: situation and way forward to improve maternal, child and adolescent nutrition in Afghanistan. PMID- 27187920 TI - Imperatives for reducing child stunting in Bangladesh. PMID- 27187918 TI - Rethinking policy perspectives on childhood stunting: time to formulate a structural and multifactorial strategy. AB - Stunting and chronic undernutrition among children in South Asia remain a major unresolved global health issue. There are compelling intrinsic and moral reasons to ensure that children attain their optimal growth potential facilitated via promotion of healthy living conditions. Investments in efforts to ensure that children's growth is not faltered also have substantial instrumental benefits in terms of cognitive and economic development. Using the case of India, we critique three prevailing approaches to reducing undernutrition among children: an over reliance on macroeconomic growth as a potent policy instrument, a disproportionate focus on interpreting undernutrition as a demand-side problem and an over-reliance on unintegrated single-factorial (one at a time) approaches to policy and research. Using existing evidence, we develop a case for support led policy approach with a focus on integrated and structural factors to addressing the problem of undernutrition among children in India. Key messages Eliminating child undernutrition is important from an intrinsic perspective and offers considerable instrumental benefits to individual and society. Evidence suggests that an exclusive reliance on a growth-mediated strategy to eliminate stunting needs to be reconsidered, suggesting the need for a substantial support led strategy. Interpreting and addressing undernutrition as a demand-side problem with proximal single-factorial interventions is futile. There is an urgent need to develop interventions that address the broader structural and upstream causes of child undernutrition. PMID- 27187921 TI - Reducing stunting in Bhutan: an achievable national goal. PMID- 27187922 TI - Reducing stunting in India: what investments are needed? PMID- 27187923 TI - Stop stunting: Pakistan perspective on how this could be realized. PMID- 27187924 TI - Stunting in Nepal: looking back, looking ahead. PMID- 27187925 TI - Using the TIDieR Checklist to Standardize the Description of a Functional Strength Training Intervention for the Upper Limb After Stroke. AB - BACKGROUND AND PURPOSE: Published reports of intervention in randomized controlled trials are often poorly described. The Template for Intervention Description and Replication (TIDieR) checklist has been recently developed to improve the reporting of interventions. The aim of this article is to describe a therapy intervention used in the stroke rehabilitation trial, "Clinical Efficacy of Functional Strength Training for Upper Limb Motor Recovery Early After Stroke: Neural Correlates and Prognostic Indicators" (FAST-INdICATE), using TIDieR. METHODS: The functional strength training intervention used in the FAST-INdICATE trial was described using TIDieR so that intervention can be replicated by both clinicians, who may implement it in practice, and researchers, who may deliver it in future research. The usefulness of TIDieR in the context of a complex stroke rehabilitation intervention was then discussed. RESULTS AND DISCUSSION: The TIDieR checklist provided a systematic way of describing a treatment intervention used in a clinical trial of stroke rehabilitation. Clarification is needed regarding several aspects of the TIDieR checklist, including in which section to report about the development of the intervention in pilot studies, results of feasibility studies; overlap between training and procedures for assessing fidelity; and where to publish supplementary material so that it remains in the public domain. CONCLUSIONS: TIDieR is a systematic way of reporting the intervention delivered in a clinical trial of a complex intervention such as stroke rehabilitation. This approach may also have value for standardizing intervention in clinical practice.Video abstract available for more insights from the authors (see Supplemental Digital Content 1, http://links.lww.com/JNPT/A131). PMID- 27187927 TI - The Use of Long Acting Reversible Contraceptives and the Relationship between Discontinuation Rates due to Menopause and to Female and Male Sterilizations. AB - Introduction Women require effective contraception until they reach menopause. The long acting reversible contraceptives (LARC) and the depot medroxyprogesterone acetate (DMPA, Depo-Provera(r), Pfizer, Puurs, Belgium) are great options and can replace possible sterilizations. Purpose To assess the relationship between the use of LARCs and DMPA and terminations ascribed to menopause and sterilizations in a Brazilian clinic. Methods We reviewed the records of women between 12 and 50 years of age attending the clinic that chose to use a LARC method or DMPA. Cumulative termination rates due to sterilization or because the woman had reached menopause were computed using single decrement life-table analysis over 32 years. We also examined all records of surgical sterilization at our hospital between the years 1980-2012. Results Three hundred thirty-two women had continuously used the same contraceptive until menopause, and 555 women had discontinued the method because they or their partners underwent sterilization. From year 20 to year 30 of use, levonorgestrel intrauterine-releasing system (LNG-IUS - Mirena(r), Bayer Oy, Turku, Finland; available since 1980), copper intrauterine device (IUD - available since 1980) and DMPA users showed a trend of cumulative higher discontinuation rates due to menopause when compared with the discontinuation rates due to sterilization. Over the study period, a steep decline in the use of sterilization occurred. Conclusion Over the past 15 years of research we have observed a trend: women usually preferred to continue using LARC methods or DMPA until menopause rather than decide for sterilization, be it their own, or their partners'. The annual number of sterilizations dropped in the same period. The use of LARC methods and DMPA until menopause is an important option to avoid sterilization, which requires a surgical procedure with potential complications. PMID- 27187928 TI - Quality of Life of Pregnant Women Living with HIV/AIDS. AB - Objective to evaluate the quality of life of HIV positive (HIV+) pregnant women using the HIV/AIDS Target Quality of Life (HAT-QoL) instrument. Methods cross sectional study, conducted between May 2014 and November 2015, with HIV+ pregnant women selected by convenience sampling. Sociodemographic and behavioral data were collected through interviews, and the HAT-QoL questionnaire was applied. Clinical and laboratorial data were collected from medical records. Results twenty-seven pregnant women participated in the study. Their mean age was 27 years (standard deviation - SD: 7.3). The majority (59%) had up to 8 years of education, 52% identified themselves as white, 56% were unemployed, and 59% had a household income higher than the minimum wage. The mean infection time by the virus was 68.4 months (5.7 years). The majority (74%) were contaminated with HIV through sexual intercourse, and 67% declared not having a HIV+ relative. Regarding the use of condoms, 41% reported using them sporadically, and the same number did not have proper knowledge about them. Only 23 patients (85%) reported having been prescribed antiretrovirals. Fourteen (64%) had a CD4 count higher than 500 cells/mm(3), and 13 pregnant women (59%) had an undetectable viral load. The scores from the quality of life questionnaire dimensions that were more affected are: infection "disclosure concerns" (mean: 39.8; SD: 27.1), followed by "financial concerns" (mean: 49.1; SD: 36), and "HIV acceptance" (mean: 49.1; SD: 35.8). The dimension with the best score was "medication concerns" (mean: 80.8; SD: 26.5). Conclusion quality of life has been increasingly used as a clinical outcome evaluation parameter. The results of this study contribute to the establishment of interventions based on the needs of HIV+ pregnant women. PMID- 27187929 TI - Molecular Subtypes of Breast Cancer Are Not Associated with the Clinical Under- or Overstaging of Breast Cancer. AB - Purpose to evaluate the agreement between the clinical and pathological stagings of breast cancer based on clinical and molecular features. Methods this was a cross-sectional study, in which clinical, epidemiological and pathological data were collected from 226 patients who underwent surgery at the Prof. Dr. Jose Aristodemo Pinotti Women's Hospital (CAISM/Unicamp) from January 2008 to September 2010. Patients were staged clinically and pathologically, and were classified as: understaged, when the clinical staging was lower than the pathological staging; correctly staged, when the clinical staging was the same as the pathological one; and overstaged, when the clinical staging was greater than the pathological staging. Results understaged patients were younger (52.2 years; p < 0.01) and more symptomatic at diagnosis (p = 0.04) when compared with correctly or overstaged patients. Clinicopathological surrogate subtype, menopausal status, parity, hormone replace therapy and histology were not associated with differences in staging. Women under 57 years of age were clinically understaged mainly due to underestimation of T (tumor staging) (p < 0.001), as were the premenopausal women (p < 0.01). Patients whose diagnosis was made due to clinical complaints, and not by screening, were clinically understaged due to underestimation of N (lymph nodes staging) (p < 0.001). Conclusion the study shows that the clinicopathological surrogate subtype is not associated with differences in staging, while younger women diagnosed because of clinical complaints tend to have their breast tumors understaged during clinical evaluation. PMID- 27187930 TI - Authentication of Gentiana straminea Maxim. and its substitutes based on chemical profiling of iridoids using liquid chromatography with mass spectrometry. AB - A liquid chromatography-electrospray ionization-ion-trap mass spectrometry (MSn ) method was established and applied for authentication of Gentiana straminea from the four substitutes, G. tibetica, G. lhassica, G. waltonii and G. robusta, based on chemical profiling of the principal iridoid glucosides aided by a quadrupole time-of-flight mass spectrometry. The fragmentation pathways of the three representative iridoid glucosides, loganic acid, gentiopicroside and sweroside, were investigated by MSn analysis in negative ion mode, which assisted the characterization of analogs detected in the chromatographic profiling of the tested Gentiana species. In total, 25 iridoids were identified or tentatively characterized from G. straminea and four substitutes, in which 7-O-(4''-O glucosyl)coumaroyl-loganic acid and 7-O-coumaroyl-loganic acid are diagnostic in G. straminea and can serve as the proposed chemical markers to discriminate it from morphologically similar substitutes. PMID- 27187931 TI - Weighing the options for limiting surplus animals. AB - The unsustainability of many animal programs managed by zoos and aquariums has brought renewed attention to unresolved questions about various management strategies. Solving the "sustainability crisis" for many species will require housing more adults and producing more offspring than there are existing spaces in accredited zoos and aquariums. Careful reproductive management is central to addressing this challenge, but opinions differ about which management strategies are best for an individual, for a species, for an institution, or for a country or region. The primary options for limiting the number of animals that would be surplus to the population are to prevent reproduction or to euthanize. However, there is much misunderstanding about methods for controlling reproduction, in particular about contraceptives and species differences in their effects. Careful weighing of all the options is called for. Lifetime Reproductive Planning may help increase breeding success through careful reproductive management but cannot eliminate production of surplus animals. Limiting reproduction does not address the problem of animals already in the population. Despite best efforts and planning, consistently hitting target numbers for a population may never be achieved. Increasing capacity provides a temporary patch when targets are exceeded, but is not a long-term solution, since each generation potentially produces even more individuals needing even more space. Welfare considerations should be included in discussions of management euthanasia and its alternatives. Such discussions will be most productive if based on full awareness of the advantages and disadvantages of all the options. Zoo Biol. 35:183-186, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27187932 TI - Sensitive determination of neurotransmitters in urine by microchip electrophoresis with multiple-concentration approaches combining field-amplified and reversed-field stacking. AB - Microchip electrophoresis (MCE) is particularly attractive as it provides high sensitivity and selectivity, short analysis time and low sample consumption. An on-line preconcentration strategy combining field-amplified stacking (FASS) and reversed-field stacking (RFS) was developed for efficient and sensitive analysis of neurotransmitters in real urine samples by MCE with laser induced fluorescence (LIF) detection. In this study, the multiple-preconcentration strategy greatly improves the sensitivity enhancement and surpass other conventional analytical methods for neurotransmitters detection. Under optimal conditions, the separation of three neurotransmitters (dopamine, norepinephrine and serotonin), was achieved within 3min with limits of detection (S/N=3) of 1.69, 2.35, and 2.73nM, respectively. The detection sensitivities were improved by 201-, 182-, and 292 fold enhancement, for the three neurotransmitters respectively. Other evaluation parameters such as linear correlation coefficients were considered as satisfactory. A real urine sample was analyzed with recoveries of 101.8-106.4%. The proposed FASS-RFS-MCE method was characterized in terms of precision, linearity, accuracy and successfully applied for rapid and sensitive determination of three neurotransmitters in human urine. PMID- 27187933 TI - Decreased OxLDL uptake and cholesterol efflux in THP1 cells elicited by cortisol and by cortisone through 11beta-hydroxysteroid dehydrogenase type 1. AB - BACKGROUND AND AIMS: Data about glucocorticoids role in the development of atherosclerosis are controversial showing different effects in human than in experimental animal models. Atherosclerosis is the result of a chronic inflammatory response to an injured endothelium where an uncontrolled uptake of OxLDL by macrophages triggers the development of foam cells, the main component of fatty streaks in atherosclerotic plaque. There are few data about the direct effect of glucocorticoids in macrophages of atherosclerotic plaque. The aim of the study was to elucidate the role of glucocorticoids in the development of foam cells in atherosclerosis initiation. METHODS: For this purpose we used THP1 cells differentiated to macrophages with phorbol esters and incubated with OxLDL alone or with cortisol or cortisone. THP1 cells were also incubated with cortisone plus an inhibitor of 11beta-hydroxysteroid dehydrogenase 1 (11betaHSD1) activity to determine the role of this enzyme on glucocorticoid action in this process. RESULTS: Ours results showed that cortisol and cortisone decreased significantly the inflammation promoted by OxLDL, and also diminished the expression of genes involved in influx and efflux of cholesterol resulting in a reduced lipid accumulation. Likewise cortisol and cortisone decreased 11betaHSD1 expression in THP1 cells. The presence of the inhibitor of 11betaHSD1 abolished all the effects elicited by cortisone. CONCLUSION: Our results indicate a direct effect of glucocorticoids on macrophages braking atherosclerosis initiation, reducing pro inflammatory markers and OxLDL uptake and cholesterol re-esterification, but also inhibiting cholesterol output. These effects appear to be mediated, at least in part, by 11betaHSD1 activity. PMID- 27187935 TI - DISC1, astrocytes and neuronal maturation: a possible mechanistic link with implications for mental disorders. AB - Disrupted-In-Schizophrenia 1 (DISC1) is a genetic risk factor implicated in major mental disorders that involve disrupted neurodevelopment and synaptic signaling. Glial cells such as astrocytes can regulate neuronal and synaptic maturation. Although astrocytes express DISC1, the role of astrocyte DISC1 in synaptic regulation remains unknown. We expressed a pathogenic, dominant-negative form of DISC1, mutant DISC1, in astrocytes to elucidate the roles of astrocytic DISC1 in maturation of dendrites and excitatory and inhibitory synapses using a co-culture model. We found that wild-type primary neurons exhibited less elaborated dendritic arborization when co-cultured with astrocytes that express mutant DISC1, compared to control astrocytes. We observed significantly decreased density of excitatory but not inhibitory synapses on wild-type primary neurons that were co-cultured with astrocytes that express mutant DISC1, compared to control astrocytes. Treatment of co-cultures with D-serine restored dendritic development and density of excitatory synapses. Our findings show for the first time that mutant DISC1 diminished the capacity of astrocytes to support dendritic and synaptic maturation in co-cultured neurons, and that D-serine can restore the dendritic and synaptic abnormalities. The results provide a new insight into the mechanisms whereby genetic risk factors within astrocytes could contribute the pathogenesis of psychiatric disorders. Expression of mutant DISC1 (mDISC1) in astrocytes (A) decreases binding of endogenous DISC1 to serine racemase (SR) and production of D-serine (blue triangles) from L-serine (red triangles). As a result, neurons co-cultured with mutant DISC1 astrocytes exhibit diminished dendritic arborization (DIV10) and decreased linear density of VGLUT+(red)/PSD95 + (green) excitatory synapses (DIV14). Filled circles with arrows denote membrane transporters for D-serine. Read the Editorial Highlight for this article on doi: 10.1111/jnc.13699. PMID- 27187934 TI - Genetic and environmental risk factors for atherosclerosis regulate transcription of phosphatase and actin regulating gene PHACTR1. AB - BACKGROUND AND AIMS: Coronary artery disease (CAD) risk is associated with non coding genetic variants at the phosphatase and actin regulating protein 1(PHACTR1) gene locus. The PHACTR1 gene encodes an actin-binding protein with phosphatase regulating activity. The mechanism whereby PHACTR1 influences CAD risk is unknown. We hypothesized that PHACTR1 would be expressed in human cell types relevant to CAD and regulated by atherogenic or genetic factors. METHODS AND RESULTS: Using immunohistochemistry, we demonstrate that PHACTR1 protein is expressed strongly in human atherosclerotic plaque macrophages, lipid-laden foam cells, adventitial lymphocytes and endothelial cells. Using a combination of genomic analysis and molecular techniques, we demonstrate that PHACTR1 is expressed as multiple previously uncharacterized transcripts in macrophages, foam cells, lymphocytes and endothelial cells. Immunoblotting confirmed a total absence of PHACTR1 in vascular smooth muscle cells. Real-time quantitative PCR showed that PHACTR1 is regulated by atherogenic and inflammatory stimuli. In aortic endothelial cells, oxLDL and TNF-alpha both upregulated an intermediate length transcript. A short transcript expressed only in immune cells was upregulated in macrophages by oxidized low-density lipoprotein, and oxidized phospholipids but suppressed by lipopolysaccharide or TNF-alpha. In primary human macrophages, we identified a novel expression quantitative trait locus (eQTL) specific for this short transcript, whereby the risk allele at CAD risk SNP rs9349379 is associated with reduced PHACTR1 expression, similar to the effect of an inflammatory stimulus. CONCLUSIONS: Our data demonstrate that PHACTR1 is a key atherosclerosis candidate gene since it is regulated by atherogenic stimuli in macrophages and endothelial cells and we identify an effect of the genetic risk variant on PHACTR1 expression in macrophages that is similar to that of an inflammatory stimulus. PMID- 27187937 TI - Adaptive Fuzzy Tracking Control of Nonlinear Systems With Asymmetric Actuator Backlash Based on a New Smooth Inverse. AB - This paper is concentrated on the problem of adaptive fuzzy tracking control for an uncertain nonlinear system whose actuator is encountered by the asymmetric backlash behavior. First, we propose a new smooth inverse model which can approximate the asymmetric actuator backlash arbitrarily. By applying it, two adaptive fuzzy control scenarios, namely, the compensation-based control scheme and nonlinear decomposition-based control scheme, are then developed successively. It is worth noticing that the first fuzzy controller exhibits a better tracking control performance, although it recourses to a known slope ratio of backlash nonlinearity. The second one further removes the restriction, and also gets a desirable control performance. By the strict Lyapunov argument, both adaptive fuzzy controllers guarantee that the output tracking error is convergent to an adjustable region of zero asymptotically, while all the signals remain semiglobally uniformly ultimately bounded. Lastly, two comparative simulations are conducted to verify the effectiveness of the proposed fuzzy controllers. PMID- 27187936 TI - Efficient and mechanically robust stretchable organic light-emitting devices by a laser-programmable buckling process. AB - Stretchable organic light-emitting devices are becoming increasingly important in the fast-growing fields of wearable displays, biomedical devices and health monitoring technology. Although highly stretchable devices have been demonstrated, their luminous efficiency and mechanical stability remain impractical for the purposes of real-life applications. This is due to significant challenges arising from the high strain-induced limitations on the structure design of the device, the materials used and the difficulty of controlling the stretch-release process. Here we have developed a laser programmable buckling process to overcome these obstacles and realize a highly stretchable organic light-emitting diode with unprecedented efficiency and mechanical robustness. The strained device luminous efficiency -70 cd A(-1) under 70% strain - is the largest to date and the device can accommodate 100% strain while exhibiting only small fluctuations in performance over 15,000 stretch release cycles. This work paves the way towards fully stretchable organic light emitting diodes that can be used in wearable electronic devices. PMID- 27187938 TI - Exponential Stability for Neutral Stochastic Markov Systems With Time-Varying Delay and Its Applications. AB - In this paper, the exponential stability in p th( p > 1 )-moment for neutral stochastic Markov systems with time-varying delay is studied. The derived stability conditions comprise two forms: 1) the delay-independent stability criteria which are obtained by establishing an integral inequality and 2) the delay-dependent stability criteria which are captured by using the theory of the functional differential equations. As its applications, the obtained stability results are used to investigate the exponential stability in p th( p > 1 )-moment for the neutral stochastic neural networks with time-varying delay and Markov switching, and the globally exponential adaptive synchronization for the neutral stochastic complex dynamical systems with time-varying delay and Markov switching, respectively. On the delay-independent criteria, sufficient conditions are given in terms of M -matrix and thus are easy to check. The delay-dependent criteria are presented in the forms of the algebraic inequalities, and the least upper bound of the time-varying delay is also provided. The primary advantages of these obtained results over some recent and similar works are that the differentiability or continuity of the delay function is not required, and that the difficulty stemming from the presence of the neutral item and the Markov switching is overcome. Three numerical examples are provided to examine the effectiveness and potential of the theoretic results obtained. PMID- 27187940 TI - Event Recognition for Contactless Activity Monitoring Using Phase-Modulated Continuous Wave Radar. AB - OBJECTIVES: The use of remote sensing technologies such as radar is gaining popularity as a technique for contactless detection of physiological signals and analysis of human motion. This paper presents a methodology for classifying different events in a collection of phase modulated continuous wave radar returns. The primary application of interest is to monitor inmates where the presence of human vital signs amidst different, interferences needs to be identified. METHODS: A comprehensive set of features is derived through time and frequency domain analyses of the radar returns. The Bhattacharyya distance is used to preselect the features with highest class separability as the possible candidate features for use in the classification process. The uncorrelated linear discriminant analysis is performed to decorrelate, denoise, and reduce the dimension of the candidate feature set. Linear and quadratic Bayesian classifiers are designed to distinguish breathing, different human motions, and nonhuman motions. The performance of these classifiers is evaluated on a pilot dataset of radar returns that contained different events including breathing, stopped breathing, simple human motions, and movement of fan and water. RESULTS: Our proposed pattern classification system achieved accuracies of up to 93% in stationary subject detection, 90% in stop-breathing detection, and 86% in interference detection. CONCLUSION: Our proposed radar pattern recognition system was able to accurately distinguish the predefined events amidst interferences. SIGNIFICANCE: Besides inmate monitoring and suicide attempt detection, this paper can be extended to other radar applications such as home-based monitoring of elderly people, apnea detection, and home occupancy detection. PMID- 27187939 TI - Semisupervised Tripled Dictionary Learning for Standard-Dose PET Image Prediction Using Low-Dose PET and Multimodal MRI. AB - OBJECTIVE: To obtain high-quality positron emission tomography (PET) image with low-dose tracer injection, this study attempts to predict the standard-dose PET (S-PET) image from both its low-dose PET (L-PET) counterpart and corresponding magnetic resonance imaging (MRI). METHODS: It was achieved by patch-based sparse representation (SR), using the training samples with a complete set of MRI, L-PET and S-PET modalities for dictionary construction. However, the number of training samples with complete modalities is often limited. In practice, many samples generally have incomplete modalities (i.e., with one or two missing modalities) that thus cannot be used in the prediction process. In light of this, we develop a semisupervised tripled dictionary learning (SSTDL) method for S-PET image prediction, which can utilize not only the samples with complete modalities (called complete samples) but also the samples with incomplete modalities (called incomplete samples), to take advantage of the large number of available training samples and thus further improve the prediction performance. RESULTS: Validation was done on a real human brain dataset consisting of 18 subjects, and the results show that our method is superior to the SR and other baseline methods. CONCLUSION: This paper proposed a new S-PET prediction method, which can significantly improve the PET image quality with low-dose injection. SIGNIFICANCE: The proposed method is favorable in clinical application since it can decrease the potential radiation risk for patients. PMID- 27187942 TI - Efficient Subculture Process for Adherent Cells by Selective Collection Using Cultivation Substrate Vibration. AB - Cell detachment and reseeding are typical operations in cell culturing, often using trypsin exposure and pipetting, even though this process is known to damage the cells. Reducing the number of detachment and reseeding steps might consequently improve the overall quality of the culture, but to date this has not been an option. This study proposes the use of resonant vibration in the cell cultivation substrate to selectively release adherent calf chondrocyte cells: Some were released from the substrate and collected while others were left upon the substrate to grow to confluence as a subculture-without requiring reseeding. An out-of-plane vibration mode with a single nodal circle was used in the custom culture substrate. At a maximum vibration amplitude of 0.6 um, 84.9% of the cells adhering to the substrate were released after 3 min exposure, leaving a sufficient number of cells for passage and long-term cell culture, with the greatest cell concentration along the nodal circle where the vibration was relatively quiescent. The 72-h proliferation of the unreleased cells was 20% greater in number than cells handled using the traditional method of trypsin-EDTA (0.050%) release, pipette collection, and reseeding. Due to the vibration, it was possible to reduce the trypsin-EDTA used for selective release to only 0.025%, and in doing so the cell number after 72 h of proliferation was 42% greater in number than the traditional technique. PMID- 27187941 TI - Characterization of Axonal Spikes in Cultured Neuronal Networks Using Microelectrode Arrays and Microchannel Devices. AB - OBJECTIVE: Axonal propagation has a pivotal role in information processing in the brain. However, there has been little experimental study due to the difficulty of isolation of axons and recording their signals. Here, we developed dual chamber neuronal network interconnected with axons by integrating microchannel devices with microelectrode arrays (MEAs) to investigate axonal signals in developmental stage. METHODS: The device was composed of two chambers and microchannels between them, and hippocampal neurons were cultured in both chambers. Neuronal activity was recorded for four weeks. RESULTS: Large axonal signal was detected in microchannels, which were 137.0 +/- 8.5 MUV at 14 days in vitro (DIV). It was significantly larger than those in chambers with a similar range of signal-to noise ratio. Detection efficiency of axonal spikes was analyzed by calculating the number of active electrodes over time. We found that active electrodes were detected earlier and their number increased faster in microchannels than those in chambers. Finally, we estimated the axonal conduction velocity and 73% of axons had the velocity in range of 0.2-0.5 m/s at 14 DIV. By estimating the velocity over the cultivation period, we observed that axonal conduction velocity increased linearly over time. CONCLUSION: Using MEAs and microchannel devices, we successfully detected large axonal signals and analyzed their detection efficiency and conduction velocity. We first showed the gradual increase in conduction velocity depending on cultivation days. SIGNIFICANCE: The developed microchannel device integrated MEA may be applicable for the studies of axonal conduction in cultured neuronal networks. PMID- 27187943 TI - Bayesian Time-of-Flight for Realtime Shape, Illumination and Albedo. AB - We propose a computational model for shape, illumination and albedo inference in a pulsed time-of-flight (TOF) camera. In contrast to TOF cameras based on phase modulation, our camera enables general exposure profiles. This results in added flexibility and requires novel computational approaches. To address this challenge we propose a generative probabilistic model that accurately relates latent imaging conditions to observed camera responses. While principled, realtime inference in the model turns out to be infeasible, and we propose to employ efficient non-parametric regression trees to approximate the model outputs. As a result we are able to provide, for each pixel, at video frame rate, estimates and uncertainty for depth, effective albedo, and ambient light intensity . These results we present are state-of-the-art in depth imaging. The flexibility of our approach allows us to easily enrich our generative model. We demonstrate this by extending the original single-path model to a two-path model, capable of describing some multipath effects. The new model is seamlessly integrated in the system at no additional computational cost. Our work also addresses the important question of optimal exposure design in pulsed TOF systems. Finally, for benchmark purposes and to obtain realistic empirical priors of multipath and insights into this phenomena, we propose a physically accurate simulation of multipath phenomena. PMID- 27187944 TI - Learning to Generate Chairs, Tables and Cars with Convolutional Networks. AB - We train generative 'up-convolutional' neural networks which are able to generate images of objects given object style, viewpoint, and color. We train the networks on rendered 3D models of chairs, tables, and cars. Our experiments show that the networks do not merely learn all images by heart, but rather find a meaningful representation of 3D models allowing them to assess the similarity of different models, interpolate between given views to generate the missing ones, extrapolate views, and invent new objects not present in the training set by recombining training instances, or even two different object classes. Moreover, we show that such generative networks can be used to find correspondences between different objects from the dataset, outperforming existing approaches on this task. PMID- 27187945 TI - Cross-Domain Visual Matching via Generalized Similarity Measure and Feature Learning. AB - Cross-domain visual data matching is one of the fundamental problems in many real world vision tasks, e.g., matching persons across ID photos and surveillance videos. Conventional approaches to this problem usually involves two steps: i) projecting samples from different domains into a common space, and ii) computing (dis-)similarity in this space based on a certain distance. In this paper, we present a novel pairwise similarity measure that advances existing models by i) expanding traditional linear projections into affine transformations and ii) fusing affine Mahalanobis distance and Cosine similarity by a data-driven combination. Moreover, we unify our similarity measure with feature representation learning via deep convolutional neural networks. Specifically, we incorporate the similarity measure matrix into the deep architecture, enabling an end-to-end way of model optimization. We extensively evaluate our generalized similarity model in several challenging cross-domain matching tasks: person re identification under different views and face verification over different modalities (i.e., faces from still images and videos, older and younger faces, and sketch and photo portraits). The experimental results demonstrate superior performance of our model over other state-of-the-art methods. PMID- 27187946 TI - Dynamic Whitening Saliency. AB - General dynamic scenes involve multiple rigid and flexible objects, with relative and common motion, camera induced or not. The complexity of the motion events together with their strong spatio-temporal correlations make the estimation of dynamic visual saliency a big computational challenge. In this work, we propose a computational model of saliency based on the assumption that perceptual relevant information is carried by high-order statistical structures. Through whitening, we completely remove the second-order information (correlations and variances) of the data, gaining access to the relevant information. The proposed approach is an analytically tractable and computationally simple framework which we call Dynamic Adaptive Whitening Saliency (AWS-D). For model assessment, the provided saliency maps were used to predict the fixations of human observers over six public video datasets, and also to reproduce the human behavior under certain psychophysical experiments (dynamic pop-out). The results demonstrate that AWS-D beats state-of the-art dynamic saliency models, and suggest that the model might contain the basis to understand the key mechanisms of visual saliency. Experimental evaluation was performed using an extension to video of the well-known methodology for static images, together with a bootstrap permutation test (random label hypothesis) which yields additional information about temporal evolution of the metrics statistical significance. PMID- 27187947 TI - Co-Saliency Detection via a Self-Paced Multiple-Instance Learning Framework. AB - As an interesting and emerging topic, co-saliency detection aims at simultaneously extracting common salient objects from a group of images. On one hand, traditional co-saliency detection approaches rely heavily on human knowledge for designing hand-crafted metrics to possibly reflect the faithful properties of the co-salient regions. Such strategies, however, always suffer from poor generalization capability to flexibly adapt various scenarios in real applications. On the other hand, most current methods pursue co-saliency detection in unsupervised fashions. This, however, tends to weaken their performance in real complex scenarios because they are lack of robust learning mechanism to make full use of the weak labels of each image. To alleviate these two problems, this paper proposes a new SP-MIL framework for co-saliency detection, which integrates both multiple instance learning (MIL) and self-paced learning (SPL) into a unified learning framework. Specifically, for the first problem, we formulate the co-saliency detection problem as a MIL paradigm to learn the discriminative classifiers to detect the co-saliency object in the "instance-level". The formulated MIL component facilitates our method capable of automatically producing the proper metrics to measure the intra-image contrast and the inter-image consistency for detecting co-saliency in a purely self learning way. For the second problem, the embedded SPL paradigm is able to alleviate the data ambiguity under the weak supervision of co-saliency detection and guide a robust learning manner in complex scenarios. Experiments on benchmark datasets together with multiple extended computer vision applications demonstrate the superiority of the proposed framework beyond the state-of-the-arts. PMID- 27187948 TI - Hyperbolic Harmonic Mapping for Surface Registration. AB - Automatic computation of surface correspondence via harmonic map is an active research field in computer vision, computer graphics and computational geometry. It may help document and understand physical and biological phenomena and also has broad applications in biometrics, medical imaging and motion capture industries. Although numerous studies have been devoted to harmonic map research, limited progress has been made to compute a diffeomorphic harmonic map on general topology surfaces with landmark constraints. This work conquers this problem by changing the Riemannian metric on the target surface to a hyperbolic metric so that the harmonic mapping is guaranteed to be a diffeomorphism under landmark constraints. The computational algorithms are based on Ricci flow and nonlinear heat diffusion methods. The approach is general and robust. We employ our algorithm to study the constrained surface registration problem which applies to both computer vision and medical imaging applications. Experimental results demonstrate that, by changing the Riemannian metric, the registrations are always diffeomorphic and achieve relatively high performance when evaluated with some popular surface registration evaluation standards. PMID- 27187949 TI - Generalized Sparse Learning of Linear Models Over the Complete Subgraph Feature Set. AB - Supervised learning over graphs is an intrinsically difficult problem: simultaneous learning of relevant features from the complete subgraph feature set, in which enumerating all subgraph features occurring in given graphs is practically intractable due to combinatorial explosion. We show that 1) existing graph supervised learning studies, such as Adaboost, LPBoost, and LARS/LASSO, can be viewed as variations of a branch-and-bound algorithm with simple bounds, which we call Morishita-Kudo bounds; 2) We present a direct sparse optimization algorithm for generalized problems with arbitrary twice-differentiable loss functions, to which Morishita-Kudo bounds cannot be directly applied; 3) We experimentally showed that i) our direct optimization method improves the convergence rate and stability, and ii) L1-penalized logistic regression (L1 LogReg) by our method identifies a smaller subgraph set, keeping the competitive performance, iii) the learned subgraphs by L1-LogReg are more size-balanced than competing methods, which are biased to small-sized subgraphs. PMID- 27187950 TI - Screening Tests for Lasso Problems. AB - This paper is a survey of dictionary screening for the lasso problem. The lasso problem seeks a sparse linear combination of the columns of a dictionary to best match a given target vector. This sparse representation has proven useful in a variety of subsequent processing and decision tasks. For a given target vector, dictionary screening quickly identifies a subset of dictionary columns that will receive zero weight in a solution of the corresponding lasso problem. These columns can be removed from the dictionary prior to solving the lasso problem without impacting the optimality of the solution obtained. This has two potential advantages: it reduces the size of the dictionary, allowing the lasso problem to be solved with less resources, and it may speed up obtaining a solution. Using a geometrically intuitive framework, we provide basic insights for understanding useful lasso screening tests and their limitations. We also provide illustrative numerical studies on several datasets. PMID- 27187951 TI - Information-Theoretic Compressive Measurement Design. AB - An information-theoretic projection design framework is proposed, of interest for feature design and compressive measurements. Both Gaussian and Poisson measurement models are considered. The gradient of a proposed information theoretic metric (ITM) is derived, and a gradient-descent algorithm is applied in design; connections are made to the information bottleneck. The fundamental solution structure of such design is revealed in the case of a Gaussian measurement model and arbitrary input statistics. This new theoretical result reveals how ITM parameter settings impact the number of needed projection measurements, with this verified experimentally. The ITM achieves promising results on real data, for both signal recovery and classification. PMID- 27187952 TI - ULA-OP 256: A 256-Channel Open Scanner for Development and Real-Time Implementation of New Ultrasound Methods. AB - Open scanners offer an increasing support to the ultrasound researchers who are involved in the experimental test of novel methods. Each system presents specific performance in terms of number of channels, flexibility, processing power, data storage capability, and overall dimensions. This paper reports the design criteria and hardware/software implementation details of a new 256-channel ultrasound advanced open platform. This system is organized in a modular architecture, including multiple front-end boards, interconnected by a high-speed (80 Gb/s) ring, capable of finely controlling all transmit (TX) and receive (RX) signals. High flexibility and processing power (equivalent to 2500 GFLOP) are guaranteed by the possibility of individually programming multiple digital signal processors and field programmable gate arrays. Eighty GB of on-board memory are available for the storage of prebeamforming, postbeamforming, and baseband data. The use of latest generation devices allowed to integrate all needed electronics in a small size ( 34 cm *30 cm *26 cm). The system implements a multiline beamformer that allows obtaining images of 96 lines by 2048 depths at a frame rate of 720 Hz (expandable to 3000 Hz). The multiline beamforming capability is also exploited to implement a real-time vector Doppler scheme in which a single TX and two independent RX apertures are simultaneously used to maintain the analysis over a full pulse repetition frequency range. PMID- 27187953 TI - Investigation of Classical Pulse Sequences for Contrast-Enhanced Ultrasound Imaging With a cMUT Probe. AB - Capacitive micromachined ultrasonic transducers (cMUTs) provide promising ultrasonic technology that could become an alternative to piezoelectric probes for medical applications. cMUTs could be very valuable for contrast-enhanced ultrasound imaging based on higher harmonics detection. However, their use is restricted by the intrinsic nonlinearity of the cMUT transmitters themselves, because it is difficult to distinguish between the nonlinearity of the microbubbles and the nonlinearity arising from the emitting transducer. A number of approaches have been proposed in recent years to cancel the nonlinearity of cMUTs. However, these techniques have limitations in terms of implementation with current ultrasound scanner electronics. The solution to be comparable with classical methods should not need precharacterization of the probe or changing the bias voltage (amplitude or polarity) but does need good sensitivity and a high frame rate to avoid motion artifacts. We propose here proof of a concept of an adapted amplitude modulation sequence with cMUT where transmit elements operate alternately. We show that this method, which is currently used with piezoelectric probes, is fully applicable to cMUT probes and the intrinsic nonlinearity of the transmitter is no longer an issue. PMID- 27187954 TI - Defocus Blur-Invariant Scale-Space Feature Extractions. AB - We propose modifications to scale-space feature extraction techniques scale invariant feature transform (SIFT) and speeded up robust features (SURFs) that make the feature detection and description invariant to defocus blur. Specifically, the scale-space blob detection relies on the second derivative responses of images. Our analysis of circular defocus blur (which sufficiently approximates a real camera blur kernel) and its effect on scale-space blob detection suggests that fourth derivative-and not the usual second derivative-is optimal for detecting the blurred blobs, while multi-scale descriptors of blurred blobs are effective at establishing correspondences between the blurred images. The proposed defocus blur-invariant (DBI) scale-space feature extraction techniques-which we refer to as DBI-SIFT and DBI-SURF-do not require image deblurring nor blur kernel estimation, meaning that their accuracy does not depend on the quality of image deblurring. We offer empirical evidence of blur invariance by establishing interest point correspondences between sharp or blurred reference images and blurred target images. PMID- 27187959 TI - Joint Segmentation and Deconvolution of Ultrasound Images Using a Hierarchical Bayesian Model Based on Generalized Gaussian Priors. AB - This paper proposes a joint segmentation and deconvolution Bayesian method for medical ultrasound (US) images. Contrary to piecewise homogeneous images, US images exhibit heavy characteristic speckle patterns correlated with the tissue structures. The generalized Gaussian distribution (GGD) has been shown to be one of the most relevant distributions for characterizing the speckle in US images. Thus, we propose a GGD-Potts model defined by a label map coupling US image segmentation and deconvolution. The Bayesian estimators of the unknown model parameters, including the US image, the label map, and all the hyperparameters are difficult to be expressed in a closed form. Thus, we investigate a Gibbs sampler to generate samples distributed according to the posterior of interest. These generated samples are finally used to compute the Bayesian estimators of the unknown parameters. The performance of the proposed Bayesian model is compared with the existing approaches via several experiments conducted on realistic synthetic data and in vivo US images. PMID- 27187957 TI - Multi-Level Canonical Correlation Analysis for Standard-Dose PET Image Estimation. AB - Positron emission tomography (PET) images are widely used in many clinical applications, such as tumor detection and brain disorder diagnosis. To obtain PET images of diagnostic quality, a sufficient amount of radioactive tracer has to be injected into a living body, which will inevitably increase the risk of radiation exposure. On the other hand, if the tracer dose is considerably reduced, the quality of the resulting images would be significantly degraded. It is of great interest to estimate a standard-dose PET (S-PET) image from a low-dose one in order to reduce the risk of radiation exposure and preserve image quality. This may be achieved through mapping both S-PET and low-dose PET data into a common space and then performing patch-based sparse representation. However, a one-size fits-all common space built from all training patches is unlikely to be optimal for each target S-PET patch, which limits the estimation accuracy. In this paper, we propose a data-driven multi-level canonical correlation analysis scheme to solve this problem. In particular, a subset of training data that is most useful in estimating a target S-PET patch is identified in each level, and then used in the next level to update common space and improve estimation. In addition, we also use multi-modal magnetic resonance images to help improve the estimation with complementary information. Validations on phantom and real human brain data sets show that our method effectively estimates S-PET images and well preserves critical clinical quantification measures, such as standard uptake value. PMID- 27187964 TI - HEVC-Based Perceptually Adaptive Video Coding Using a DCT-Based Local Distortion Detection Probability Model. AB - Discrete Cosine Transform (DCT)-based just noticeable difference (JND) profiles have widely been applied into human perception-based video coding in order to reduce perceptual redundancy, which is one of the main goals of perceptual video coding (PVC). However, there are two problems for this approach: 1) the JND value of each transform coefficient is estimated for a fixed-sized DCT kernel (e.g., 8 * 8), but flexible coding structures with variable-sized transform units have been utilized in standard video coding frameworks, such high efficiency video coding (HEVC) and 2) the DCT transform coefficients are suppressed by the amounts of JND values for the removal of perceptual redundancy, but the DCT transform coefficients of residues are not sufficiently suppressed due to many small transform coefficient values in mid- and high-frequency regions below the JND values. In order to solve these problems, we propose a more generalized visibility model in the DCT domain, called the DCT-based local distortion detection probability (LDDP) model that can estimate a degree of distortion visibility for any distribution of the transform coefficients of any sized DCT kernel for residues. Furthermore, we propose an HEVC-compliant LDDP-based PVC scheme where transform coefficients are sufficiently suppressed based on the LDDP model. The proposed PVC scheme is implemented in the HEVC Test Model (HM 11.0) reference software to show the effectiveness of the LDDP-based PVC scheme. Objective and subjective tests for encoded test sequences are performed. The experimental results show that the LDDP-based PVC scheme achieves a significant performance improvement of bitrate reduction at the similar visual quality levels compared with the original HM 11.0. PMID- 27187960 TI - Fast Single Image Super-Resolution Using a New Analytical Solution for l2 - l2 Problems. AB - This paper addresses the problem of single image super-resolution (SR), which consists of recovering a high-resolution image from its blurred, decimated, and noisy version. The existing algorithms for single image SR use different strategies to handle the decimation and blurring operators. In addition to the traditional first-order gradient methods, recent techniques investigate splitting based methods dividing the SR problem into up-sampling and deconvolution steps that can be easily solved. Instead of following this splitting strategy, we propose to deal with the decimation and blurring operators simultaneously by taking advantage of their particular properties in the frequency domain, leading to a new fast SR approach. Specifically, an analytical solution is derived and implemented efficiently for the Gaussian prior or any other regularization that can be formulated into an l2 -regularized quadratic model, i.e., an l2 - l2 optimization problem. The flexibility of the proposed SR scheme is shown through the use of various priors/regularizations, ranging from generic image priors to learning-based approaches. In the case of non-Gaussian priors, we show how the analytical solution derived from the Gaussian case can be embedded into traditional splitting frameworks, allowing the computation cost of existing algorithms to be decreased significantly. Simulation results conducted on several images with different priors illustrate the effectiveness of our fast SR approach compared with existing techniques. PMID- 27187966 TI - Spatiotemporal Statistics for Video Quality Assessment. AB - It is an important task to design models for universal no-reference video quality assessment (NR-VQA) in multiple video processing and computer vision applications. However, most existing NR-VQA metrics are designed for specific distortion types, which are not often aware in practical applications. A further deficiency is that the spatial and temporal information of videos is hardly considered simultaneously. In this paper, we propose a new NR-VQA metric based on the spatiotemporal natural video statistics in 3D discrete cosine transform (3D DCT) domain. In the proposed method, a set of features are first extracted based on the statistical analysis of 3D-DCT coefficients to characterize the spatiotemporal statistics of videos in different views. These features are used to predict the perceived video quality via the efficient linear support vector regression model afterward. The contributions of this paper are: 1) we explore the spatiotemporal statistics of videos in the 3D-DCT domain that has the inherent spatiotemporal encoding advantage over other widely used 2D transformations; 2) we extract a small set of simple but effective statistical features for video visual quality prediction; and 3) the proposed method is universal for multiple types of distortions and robust to different databases. The proposed method is tested on four widely used video databases. Extensive experimental results demonstrate that the proposed method is competitive with the state-of-art NR-VQA metrics and the top-performing full-reference VQA and reduced reference VQA metrics. PMID- 27187968 TI - Optimal Fungal Space Searching Algorithms. AB - Previous experiments have shown that fungi use an efficient natural algorithm for searching the space available for their growth in micro-confined networks, e.g., mazes. This natural "master" algorithm, which comprises two "slave" sub algorithms, i.e., collision-induced branching and directional memory, has been shown to be more efficient than alternatives, with one, or the other, or both sub algorithms turned off. In contrast, the present contribution compares the performance of the fungal natural algorithm against several standard artificial homologues. It was found that the space-searching fungal algorithm consistently outperforms uninformed algorithms, such as Depth-First-Search (DFS). Furthermore, while the natural algorithm is inferior to informed ones, such as A*, this under performance does not importantly increase with the increase of the size of the maze. These findings suggest that a systematic effort of harvesting the natural space searching algorithms used by microorganisms is warranted and possibly overdue. These natural algorithms, if efficient, can be reverse-engineered for graph and tree search strategies. PMID- 27187967 TI - A Robust Parameterization of Human Gait Patterns Across Phase-Shifting Perturbations. AB - The phase of human gait is difficult to quantify accurately in the presence of disturbances. In contrast, recent bipedal robots use time-independent controllers relying on a mechanical phase variable to synchronize joint patterns through the gait cycle. This concept has inspired studies to determine if human joint patterns can also be parameterized by a mechanical variable. Although many phase variable candidates have been proposed, it remains unclear which, if any, provide a robust representation of phase for human gait analysis or control. In this paper we analytically derive an ideal phase variable (the hip phase angle) that is provably monotonic and bounded throughout the gait cycle. To examine the robustness of this phase variable, ten able-bodied human subjects walked over a platform that randomly applied phase-shifting perturbations to the stance leg. A statistical analysis found the correlations between nominal and perturbed joint trajectories to be significantly greater when parameterized by the hip phase angle (0.95+) than by time or a different phase variable. The hip phase angle also best parameterized the transient errors about the nominal periodic orbit. Finally, interlimb phasing was best explained by local (ipsilateral) hip phase angles that are synchronized during the double-support period. PMID- 27187971 TI - A Muscle Fibre Conduction Velocity Tracking ASIC for Local Fatigue Monitoring. AB - Electromyography analysis can provide information about a muscle's fatigue state by estimating Muscle Fibre Conduction Velocity (MFCV), a measure of the travelling speed of Motor Unit Action Potentials (MUAPs) in muscle tissue. MFCV better represents the physical manifestations of muscle fatigue, compared to the progressive compression of the myoelectic Power Spectral Density, hence it is more suitable for a muscle fatigue tracking system. This paper presents a novel algorithm for the estimation of MFCV using single threshold bit-stream conversion and a dedicated application-specified integrated circuit (ASIC) for its implementation, suitable for a compact, wearable and easy to use muscle fatigue monitor. The presented ASIC is implemented in a commercially available AMS 0.35 [Formula: see text] CMOS technology and utilizes a bit-stream cross-correlator that estimates the conduction velocity of the myoelectric signal in real time. A test group of 20 subjects was used to evaluate the performance of the developed ASIC, achieving good accuracy with an error of only 3.2% compared to Matlab. PMID- 27187970 TI - An Eigen-Binding Site Based Method for the Analysis of Anti-EGFR Drug Resistance in Lung Cancer Treatment. AB - We explore the drug resistance mechanism in non-small cell lung cancer treatment by characterizing the drug-binding site of a protein mutant based on local surface and energy features. These features are transformed to an eigen-binding site space and used for drug resistance level prediction and analysis. PMID- 27187972 TI - The Effect of Global and Local Damping on the Perception of Hardness. AB - In tele-operation systems, damping is often injected to guarantee system stability during contact with hard objects. In this study, we used psychophysical experiments to assess the effect of adding damping on the user's perception of object hardness. In Experiments 1 and 2, combinations of stiffness and damping were tested to assess their effect on perceived hardness. In both experiments, two tasks were used: an in-contact task, starting at the object's surface, and a contact-transition task, including a free-air movement. In Experiment 3, the difference between inserting damping globally (equally throughout the workspace) and locally (inside the object only) was tested. In all experiments, the correlation between the participant's perceptual decision and force and position data was also investigated. Experiments 1 and 2 show that when injecting damping globally, perceived hardness slightly increased for an in-contact task, while it decreased considerably for a contact-transition task. Experiment 3 shows that this effect was mainly due to inserting damping globally, since there was a large perceptual difference between inserting damping globally and locally. The force and position parameters suggest that participants used the same force profile during the two movements of one trial and assessed the system's reaction to this force to perceive hardness. PMID- 27187973 TI - A Memristive Multilayer Cellular Neural Network With Applications to Image Processing. AB - The memristor has been extensively studied in electrical engineering and biological sciences as a means to compactly implement the synaptic function in neural networks. The cellular neural network (CNN) is one of the most implementable artificial neural network models and capable of massively parallel analog processing. In this paper, a novel memristive multilayer CNN (Mm-CNN) model is presented along with its performance analysis and applications. In this new CNN design, the memristor crossbar circuit acts as the synapse, which realizes one signed synaptic weight with a pair of memristors and performs the synaptic weighting compactly and linearly. Moreover, the complex weighted summation is executed in an efficient way with a proper design of Mm-CNN cell circuits. The proposed Mm-CNN has several merits, such as compactness, nonvolatility, versatility, and programmability of synaptic weights. Its performance in several image processing applications is illustrated through simulations. PMID- 27187974 TI - Extending the Peak Bandwidth of Parameters for Softmax Selection in Reinforcement Learning. AB - Softmax selection is one of the most popular methods for action selection in reinforcement learning. Although various recently proposed methods may be more effective with full parameter tuning, implementing a complicated method that requires the tuning of many parameters can be difficult. Thus, softmax selection is still worth revisiting, considering the cost savings of its implementation and tuning. In fact, this method works adequately in practice with only one parameter appropriately set for the environment. The aim of this paper is to improve the variable setting of this method to extend the bandwidth of good parameters, thereby reducing the cost of implementation and parameter tuning. To achieve this, we take advantage of the asymptotic equipartition property in a Markov decision process to extend the peak bandwidth of softmax selection. Using a variety of episodic tasks, we show that our setting is effective in extending the bandwidth and that it yields a better policy in terms of stability. The bandwidth is quantitatively assessed in a series of statistical tests. PMID- 27187975 TI - Exponential Synchronization of Memristive Neural Networks With Delays: Interval Matrix Method. AB - This paper considers the global exponential synchronization of drive-response memristive neural networks (MNNs) with heterogeneous time-varying delays. Because the parameters of MNNs are state-dependent, the MNNs may exhibit unexpected parameter mismatch when different initial conditions are chosen. Therefore, traditional robust control scheme cannot guarantee the synchronization of MNNs. Under the framework of Filippov solution, the drive and response MNNs are first transformed into systems with interval parameters. Then suitable controllers are designed to overcome the problem of mismatched parameters and synchronize the coupled MNNs. Based on some novel Lyapunov functionals and interval matrix inequalities, several sufficient conditions are derived to guarantee the exponential synchronization. Moreover, adaptive control is also investigated for the exponential synchronization. Numerical simulations are provided to illustrate the effectiveness of the theoretical analysis. PMID- 27187978 TI - A Framework of Camera Source Identification Bayesian Game. AB - Image forensics with the presence of an adversary, such as the interplay between the sensor-based camera source identification (CSI) and the fingerprint-copy attack, has attracted increasing attention recently. In this paper, we propose a framework of CSI game with both complete information and incomplete information. A noise level-based counter anti-forensic method is presented to detect the potential fingerprint-copy attack, and unlike the state-of-the-art countermeasure of the triangle test, it does not need to collect the candidate image set. With the existence of countermeasure, a rational forger needs to balance the tradeoff between synthesizing source information and leaving new detectable evidence of raising the noise level of a forged image. The mixed-strategy other than the sequential-move assumption is adopted to solve the games. The Bayesian game is introduced to address the information asymmetry in practice. The Nash equilibrium of both the complete information game and Bayesian game are theoretically analyzed, and the expected Nash equilibrium payoff of a Bayesian game is obtained. Nash equilibrium receiver operating characteristic curves are adopted to evaluate the detection performance. Simulation results show that the information asymmetry can remarkably affect the final detection performance. To our knowledge, this paper is the first attempt in analyzing a Bayesian forensic game with practical information asymmetry. PMID- 27187979 TI - A New Deformation Model of Biological Tissue for Surgery Simulation. AB - A novel meshless deformation model of biological soft tissue, which is mainly based on the radial basis function point interpolation, is presented for interactive simulation applications such as virtual surgery simulators. Compared with conventional mesh models, the proposed model is particularly suitable for simulating large deformation, sucking and cutting tasks since there is no need to maintain grid information. Kelvin viscoelasticity, which represents relaxation, creep, and hysteresis of soft tissue, is integrated into the proposed model, making the simulation much more realistic than many existing meshless models. To verify the validity of the proposed model, a biomechanical test was performed on real-life biological tissue and the results show that the maximum relative error between the forces from the biomechanical test and those obtained from the model is less than 5.8%. The proposed model was also implemented on a neurosurgery simulator, which showed that the deformation of the brain tumor can be simulated in a high degree of accuracy with real-time performance. In particular, the error and distortion from the remeshing process inherited in conventional mesh models when deformation is large are avoided. PMID- 27187980 TI - Nanoscale Particulate Matter from Urban Traffic Rapidly Induces Oxidative Stress and Inflammation in Olfactory Epithelium with Concomitant Effects on Brain. AB - BACKGROUND: Rodent models for urban air pollution show consistent induction of inflammatory responses in major brain regions. However, the initial impact of air pollution particulate material on olfactory gateways has not been reported. OBJECTIVE: We evaluated the olfactory neuroepithelium (OE) and brain regional responses to a nanosized subfraction of urban traffic ultrafine particulate matter (nPM, < 200 nm) in vivo, ex vivo, and in vitro. METHODS: Adult mice were exposed to reaerosolized nPM for 5, 20, and 45 cumulative hours over 3 weeks. The OE, the olfactory bulb (OB), the cerebral cortex, and the cerebellum were analyzed for oxidative stress and inflammatory responses. Acute responses of the OE to liquid nPM suspensions were studied with ex vivo and primary OE cultures. RESULTS: After exposure to nPM, the OE and OB had rapid increases of 4-hydroxy-2 nonenal (4-HNE) and 3-nitrotyrosine (3-NT) protein adducts, whereas the cerebral cortex and cerebellum did not respond at any time. All brain regions showed increased levels of tumor necrosis factor-alpha (TNFalpha) protein by 45 hr, with earlier induction of TNFalpha mRNA in OE and OB. These responses corresponded to in vitro OE and mixed glial responses, with rapid induction of nitrite and inducible nitric oxide synthase (iNOS), followed by induction of TNFalpha. CONCLUSIONS: These findings show the differential time course of oxidative stress and inflammatory responses to nPM between the OE and the brain. Slow cumulative transport of inhaled nPM into the brain may contribute to delayed responses of proximal and distal brain regions, with potential input from systemic factors. CITATION: Cheng H, Saffari A, Sioutas C, Forman HJ, Morgan TE, Finch CE. 2016. Nanoscale particulate matter from urban traffic rapidly induces oxidative stress and inflammation in olfactory epithelium with concomitant effects on brain. Environ Health Perspect 124:1537-1546; http://dx.doi.org/10.1289/EHP134. PMID- 27187981 TI - Associations of Peripubertal Serum Dioxin and Polychlorinated Biphenyl Concentrations with Pubertal Timing among Russian Boys. AB - BACKGROUND: Dioxins, furans, and polychlorinated biphenyls (PCBs), dioxin-like and non-dioxin-like, have been linked to alterations in puberty. OBJECTIVES: We examined the association of peripubertal serum levels of these compounds [and their toxic equivalents (TEQs)] with pubertal onset and maturity among Russian boys enrolled at ages 8-9 years and followed prospectively through ages 17-18 years. METHODS: At enrollment, 473 boys had serum dioxin-like compounds and PCBs measured. At the baseline visit and annually until age 17-18 years, a physician performed pubertal staging [genitalia (G), pubarche (P), and testicular volume (TV)]. Three hundred fifteen subjects completed the follow-up visit at 17-18 years of age. Pubertal onset was defined as TV > 3 mL, G2, or P2. Sexual maturity was defined as TV >= 20 mL, G5, or P5. Multivariable interval-censored models were used to evaluate associations of lipid-standardized concentrations with pubertal timing. RESULTS: Medians (interquartile ranges) of the sum of dioxin like compounds, TEQs, and non-dioxin-like PCBs were 362 pg/g lipid (279-495), 21.1 pg TEQ/g lipid (14.4-33.2), and 250 ng/g lipid (164-395), respectively. In adjusted models, the highest compared to lowest TEQ quartile was associated with later pubertal onset [TV = 11.6 months (95% CI: 3.8, 19.4); G2 = 10.1 months (95% CI: 1.4, 18.8)] and sexual maturity [TV = 11.6 months (95% CI: 5.7, 17.6); G5 = 9.7 months (95% CI: 3.1, 16.2)]. However, the highest compared to the lowest quartile of non-dioxin-like PCBs, when co-adjusted by TEQs, was associated with earlier pubertal onset [TV = -8.3 months (95% CI:-16.2, -0.3)] and sexual maturity [TV = -6.3 months (95% CI:-12.2, -0.3); G5 = -7.2 months (95% CI:-13.8, 0.6)]; the non-dioxin-like PCB associations were only significant when adjusted for TEQs. TEQs and PCBs were not significantly associated with pubic hair development. CONCLUSIONS: Our results suggest that TEQs may delay, while non dioxin-like PCBs advance, the timing of male puberty. Citation: Burns JS, Lee MM, Williams PL, Korrick SA, Sergeyev O, Lam T, Revich B, Hauser R. 2016. Associations of peripubertal serum dioxin and polychlorinated biphenyl concentrations with pubertal timing among Russian boys. Environ Health Perspect 124:1801-1807; http://dx.doi.org/10.1289/EHP154. PMID- 27187983 TI - Safety and Effectiveness of the Nav-6 Filter in Preventing Distal Embolization During Jetstream Atherectomy of Infrainguinal Peripheral Artery Lesions. AB - BACKGROUND: The risk of distal embolization (DE) during infrainguinal peripheral artery interventions (PAI) is often mitigated by the use of embolic protection devices. There are limited data on the use of filters with the Jetstream (JS) atherectomy device, a rotational cutter with aspiration capacity. The Nav-6 filter is uniquely suited for use with the JS due to its wire compatibility and detachment from the filter; however, data on the off-label use of this combination have not been reported. METHODS: Consecutive patients between October 2008 and April 2015 undergoing endovascular infrainguinal PAI with JS were analyzed as part of the Excellence in Peripheral Artery Disease (XL-PAD) registry (NCT01904851). Patients were divided into two subgroups with Nav-6 filter use vs no filter use. Descriptive and univariate analyses were performed. RESULTS: Among 141 patients (mean age, 67.8 +/- 10.8 years; 169 lesions) included in this study, the Nav-6 filter was used in 82 (59%). Use of a filter was more frequent in longer lesions (146 +/- 106 mm vs 91 +/- 72 mm; P=.01), in more severe stenoses (95% vs 87%; P=.04), and in chronic total occlusions (33% vs 8.3%; P=.01). Patients receiving filters had longer procedure duration (102 +/- 51 min vs 66 +/ 41 min; P=.01) and longer fluoroscopy times (31 +/- 16 min vs 21 +/- 10 min; P<.001). Use of the Nav-6 filter with the JS during PAI was associated with numerically lower rates of DE (1.8% vs 8%; P=.10) and similar rates of death and amputation. At 12 months, the target-lesion revascularization rate was higher in the filter group (22% vs 2.7%; P=.02), likely secondary to use of the filter in more complex lesions. CONCLUSION: Nav-6 filter during JS atherectomy was predominantly used during complex infrainguinal PAI and was associated with less occurrence of DE. PMID- 27187982 TI - Bisphenol A and Adiposity in an Inner-City Birth Cohort. AB - BACKGROUND: Early-life exposure to the endocrine disruptor bisphenol A (BPA) may contribute to the development of obesity. Prospective evidence in humans on this topic is limited. OBJECTIVES: We examined prenatal and early-childhood BPA exposures in relation to childhood measures of adiposity in the Columbia Center for Children's Environmental Health (CCCEH) New York City birth cohort. METHODS: BPA concentrations were measured in prenatal (n = 375) and child ages 3 (n = 408) and 5 years (n = 518) spot urine samples. Childhood anthropometric and bioelectrical impedance outcomes included body mass index z-scores (BMIZ) at 5 and 7 years, and fat mass index (FMI), percent body fat (%BF), and waist circumference (WC) at 7 years. Associations were evaluated using multiple linear regression with continuous and tertile BPA concentrations. RESULTS: Prenatal urinary BPA concentrations were positively associated with child age 7 FMI (beta = 0.31 kg/m2; 95% CI: 0.01, 0.60, p = 0.04), %BF (beta = 0.79; 95% CI: 0.03, 1.55, p = 0.04), and WC (beta = 1.29 cm; 95% CI: 0.29, 2.30, p = 0.01), but not BMIZ, or change in BMIZ between ages 5 and 7 years (all p-values > 0.1). FMI results were sex-specific. Child urinary BPA concentrations were not associated with child anthropometric outcomes (all p-values > 0.05). CONCLUSIONS: Analyses of the CCCEH longitudinal birth cohort found associations between prenatal urinary BPA concentrations and FMI, %BF, and WC. Our results suggest that prenatal BPA exposure may contribute to developmental origins of adiposity. These findings are consistent with several prior studies, raising concern about the pervasiveness of BPA. CITATION: Hoepner LA, Whyatt RM, Widen EM, Hassoun A, Oberfield SE, Mueller NT, Diaz D, Calafat AM, Perera FP, Rundle AG. 2016. Bisphenol A and adiposity in an inner-city birth cohort. Environ Health Perspect 124:1644-1650; http://dx.doi.org/10.1289/EHP205. PMID- 27187984 TI - Comparative Analysis of Radial Versus Femoral Diagnostic Cardiac Catheterization Procedures in a Cardiology Training Program. AB - OBJECTIVES: This study was conducted to evaluate the differences in the procedural variables between transradial and transfemoral access for coronary angiography, with cardiology fellows as the primary operators. METHODS: This was a retrospective study of 163 radial and 180 femoral access diagnostic cardiac catheterization procedures, and involved cardiology fellowship trainees as primary operators. RESULTS: The radial approach was associated with significantly higher fluoroscopy time (8.0 +/- 6.97 min vs 4.25 +/- 3.01 min; P<.001), dose area product (10775 +/- 6724 MUGy/m2 vs 7952 +/- 4236 MUGy/m2; P<.001), procedure time (38.31 +/- 12.25 min vs 27 +/- 17.56 min; P<.001), procedure start to vascular access time (8.24 +/- 6.31 min vs 5.31 +/- 4.59 min; P<.001), and vascular access to procedure end time (30 +/- 15.34 min vs 21.2 +/- 9.57 min; P<.001). These differences persisted after adjusting for patients with bypass grafts and additional imaging (P<.001). The contrast amount was not significantly different between the two groups (P=.12). Procedure start to vascular access time improved significantly with fellowship training year in both the radial (9.57 +/- 6.96 min vs 8.23 +/- 6.08 min vs 5.57 +/- 4.82 min) and femoral groups (6.17 +/- 5.07 min vs 5.47 +/- 4.75 min vs 4.01 +/- 3.31 min). Fluoroscopy time showed significant difference in only the femoral access group (P=.01). Dose area product did not improve with training in either access group. CONCLUSION: Radial procedures were associated with higher radiation dose and longer procedure time. Despite decrease in total procedural time for radial cases with the level of training, total radiation dose did not decrease. PMID- 27187986 TI - Neuropsychological Impairments and Age-Related Differences in Children and Adolescents with Fetal Alcohol Spectrum Disorders. AB - BackgroundChildren and adolescents with Fetal Alcohol Spectrum Disorders (FASD) exhibit a range of physical, cognitive, behavioral, and/or learning deficits, as wells as poor executive functioning (EF). Children and adolescents with FASD often show greater impairments on complex neuropsychological tasks. However, little is known about age-related differences among children and adolescents with FASD.ObjectivesThe goals of this cross-sectional study were to explore the overall profile of neuropsychological impairments and extended previous reports on age-related differences among children and adolescents with FASD. MethodWe compared 117 children and adolescents diagnosed with an FASD (aged 5-17 years), clinically assessed on a broad range of tests covering 6 neurobehavioral domains. Data from a clinical database was used to generate profiles of neuropsychological impairments for clinically referred children and adolescents evaluated for FASD between 2001 and 2005. ResultsChildren and adolescents were impaired (relative to the norm) on a number of domains that include academic achievement, language, verbal memory, EF, visual-motor integration, and motor abilities. Older participants with FASD (relative to the norm) showed greater difficulty in areas involving EF or processing of complex information than younger participants. ConclusionsThese results suggest that for children and adolescents with FASD impairments in those areas important for independent functioning may become more pronounced with increasing age. However, further longitudinal research is needed to ascertain age changes over time. PMID- 27187987 TI - Retrieving relevant time-course experiments: a study on Arabidopsis microarrays. AB - Understanding time-course regulation of genes in response to a stimulus is a major concern in current systems biology. The problem is usually approached by computational methods to model the gene behaviour or its networked interactions with the others by a set of latent parameters. The model parameters can be estimated through a meta-analysis of available data obtained from other relevant experiments. The key question here is how to find the relevant experiments which are potentially useful in analysing current data. In this study, the authors address this problem in the context of time-course gene expression experiments from an information retrieval perspective. To this end, they introduce a computational framework that takes a time-course experiment as a query and reports a list of relevant experiments retrieved from a given repository. These retrieved experiments can then be used to associate the environmental factors of query experiment with the findings previously reported. The model is tested using a set of time-course Arabidopsis microarrays. The experimental results show that relevant experiments can be successfully retrieved based on content similarity. PMID- 27187985 TI - Rheolytic Thrombectomy for Acute Myocardial Infarction Complicated by Cardiogenic Shock. AB - OBJECTIVES: We sought to investigate the prognostic impact of rheolytic thrombectomy (RT) in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS). BACKGROUND: Very few data exist on thrombus removal before stenting in patients with AMI and CS treated with primary percutaneous coronary intervention (PCI). METHODS: Of 4023 patients who underwent PCI for AMI between 1995 and 2012, we focused on 371 patients presenting with CS at admission and separated them into two groups: the first included 63 patients treated with RT (RT group), and the remaining 308 underwent standard PCI (non-RT group). The primary endpoint was the composite of cardiac death, reinfarction, stroke, and target-vessel revascularization (TVR) at 2-year follow-up (MACE). RESULTS: The primary endpoint rate was lower in the RT-group (57.1% RT vs 70.8% non-RT; P=.04). The difference between groups was driven by a lower TVR rate (9.5% RT vs 23.4% non-RT; P=.02) and reinfarction (1.6% RT vs 9.1% non-RT; P=.04), while no difference between groups was revealed in mortality (46.0% RT vs 49.4% non-RT; P=.68) or stroke rate (1.6% RT vs 3.2% non-RT; P=.70). At multivariable analysis, the variables related to the risk of the primary endpoint were age (hazard ratio [HR], 1.036; 95% confidence interval [CI], 1.022-1.048; P<.001), three-vessel disease (HR, 1.504; 95% CI, 1.163-1.946; P=.01), RT (HR, 0.689; 95% CI, 0.476 0.998; P=.049), and successful primary PCI (HR, 0.367; 95% CI, 0.266-0.505; P<.001). CONCLUSION: RT reduces 2-year MACE rate in patients with large thrombus burden and AMI complicated by CS. PMID- 27187988 TI - Non-linear feedback control of the p53 protein-mdm2 inhibitor system using the derivative-free non-linear Kalman filter. AB - It is proven that the model of the p53-mdm2 protein synthesis loop is a differentially flat one and using a diffeomorphism (change of state variables) that is proposed by differential flatness theory it is shown that the protein synthesis model can be transformed into the canonical (Brunovsky) form. This enables the design of a feedback control law that maintains the concentration of the p53 protein at the desirable levels. To estimate the non-measurable elements of the state vector describing the p53-mdm2 system dynamics, the derivative-free non-linear Kalman filter is used. Moreover, to compensate for modelling uncertainties and external disturbances that affect the p53-mdm2 system, the derivative-free non-linear Kalman filter is re-designed as a disturbance observer. The derivative-free non-linear Kalman filter consists of the Kalman filter recursion applied on the linearised equivalent of the protein synthesis model together with an inverse transformation based on differential flatness theory that enables to retrieve estimates for the state variables of the initial non-linear model. The proposed non-linear feedback control and perturbations compensation method for the p53-mdm2 system can result in more efficient chemotherapy schemes where the infusion of medication will be better administered. PMID- 27187989 TI - Gene selection approach based on improved swarm intelligent optimisation algorithm for tumour classification. AB - A number of different gene selection approaches based on gene expression profiles (GEP) have been developed for tumour classification. A gene selection approach selects the most informative genes from the whole gene space, which is an important process for tumour classification using GEP. This study presents an improved swarm intelligent optimisation algorithm to select genes for maintaining the diversity of the population. The most essential characteristic of the proposed approach is that it can automatically determine the number of the selected genes. On the basis of the gene selection, the authors construct a variety of the tumour classifiers, including the ensemble classifiers. Four gene datasets are used to evaluate the performance of the proposed approach. The experimental results confirm that the proposed classifiers for tumour classification are indeed effective. PMID- 27187991 TI - Exchange strategy focuses on getting 'the right steps in place to ensure long term stability'. PMID- 27187990 TI - Minimum steering node set of complex networks and its applications to biomolecular networks. AB - Many systems of interests in practices can be represented as complex networks. For biological systems, biomolecules do not perform their functions alone but interact with each other to form so-called biomolecular networks. A system is said to be controllable if it can be steered from any initial state to any other final state in finite time. The network controllability has become essential to study the dynamics of the networks and understand the importance of individual nodes in the networks. Some interesting biological phenomena have been discovered in terms of the structural controllability of biomolecular networks. Most of current studies investigate the structural controllability of networks in notion of the minimum driver node sets (MDSs). In this study, the authors analyse the network structural controllability in notion of the minimum steering node sets (MSSs). They first develop a graph-theoretic algorithm to identify the MSS for a given network and then apply it to several biomolecular networks. Application results show that biomolecules identified in the MSSs play essential roles in corresponding biological processes. Furthermore, the application results indicate that the MSSs can reflect the network dynamics and node importance in controlling the networks better than the MDSs. PMID- 27187992 TI - [Personalities in the history of medicine]. PMID- 27187993 TI - Epidemic focus. Waiting in the wings: Aedes mosquitoes and flavivirus epidemics. PMID- 27187994 TI - Progress towards polio eradication worldwide, 2015-2016. PMID- 27187995 TI - [Not Available]. PMID- 27187996 TI - Professor Iuliu Suteu. PMID- 27187997 TI - [Not Available]. PMID- 27187998 TI - Preface. PMID- 27187999 TI - [Reaction on 'Risk factors and protective factors relating to suicide in the Netherlands and Flanders']. PMID- 27188000 TI - [THE IMPORTANCE OF ANTICOAGULANT THERAPY IN PATIENTS WITH ARTIAL FIBRILLATION IN STROKE PREVENTION--SUMMARY OF INTERNATIONAL DATA AND NOVEL THERAPEUTIC MODALITIES]. AB - The most common cardiogenic cause of ischaemic stroke is atrial fibrillation which increases the probability of stroke five-fold and doubles case fatality. Based on international data the incidence of atrial fibrillation is approx. 2% however this rapidly increases with age. The necessity of using oral anticoagulants in the prevention of non-valvular atrial fibrillation related stroke is decided based on estimated stroke risk. The CHADS2 and the more predictive CHA2DS2-VASc scales are used for this purpose while the bleeding risk of patients treated with anticoagulant may be estimated by the HAS-BLED scoring scale. For decades oral anticoagulation meant using vitamin-K antagonists. Based on international data we can see that rate of anticoagulation is unacceptably low, furthermore most of the anticoagulated patients aren't within the therapeutic range of INR (INR: 2-3). A lot of disadvantages of vitamin-K antagonists are known (e.g. food-drug interaction, need for regular coagulation monitoring, increased risk of bleeding), therefore compounds with new therapeutic target have been developed. The novel oral anticoagulants (NOAC) can be divided in two major subgroups: direct thrombin inhibitors (dabigatran etexilate) and Xa factor inhibitors (rivaroxaban, apixaban, edoxaban). These products are administered in fix doses, they less frequently interact with other medications or food, and regular coagulation monitoring is not needed when using these drugs. Moreover several studies have shown that they are at least as effective in the prevention of ischaemic stroke than the vitamin-K antagonists, with no more haemorrhagic complications. PMID- 27188001 TI - [THE THERAPUETIC USE OF TRANSCRANIAL MAGNETIC STIMULATION IN MAJOR DEPRESSION]. AB - The antidepressive effect of repetitive transcranial magnetic stimulation (rTMS) has been investigated for almost 20 years now. Several studies have been published aiming to identify the exact and reliable parameters leading to the desired therapeutic effect. However, the related literature shows great variability. The current overview aims to provide a comprehensive overview of factors associated with the therapeutic effect of rTMS in major depression. High frequency stimulation of the left dorsolateral prefrontal cortex (DLPFC) for 3-6 weeks leads to mood improvement comparable to the effect of antidepressive medications in 35-40% of patients. Pharmacotherapy resistant patients treated with rTMS reach remission for 3 months on average. Low frequency stimulation of the right DLPFC appears to be similarly effective, though much less investigated so far. In addition to the exact delineation of the stimulation area, treatment outcome is also related to stimulation intensity as well as the number of sessions and impulses. Considering the safety and tolerability aspects of rTMS, it might be a significant therapeutic support for therapy resistant patients. Above this, patients diagnosed with major depression might benefit from the additional positive influence of rTMS improving the effect of antidepressive medication. Based on converging research evidence, the Food and Drug Administration (FDA) agency approved the use of rTMS as a treatment option for therapy resistant major depression in 2008. So far, in Hungary rTMS is primarily considered as a promising tool in research settings only. Hopefully, patients suffering from major depression will increasingly benefit from the positive therapeutic effect of this intervention. PMID- 27188002 TI - HUNGARIAN EXPERIENCES WITH THE BELIEFS ABOUT ATTRACTIVENESS SCALE. AB - BACKGROUND AND PURPOSE: Sociocultural influences regarding bodily appearance and their psychological consequences play a considerable role in the development and maintenance of body image disturbance and eating disorders. The purpose of the study was to explore the psychometric properties of the Beliefs About Attractiveness Scale-Revised and its correlates among young adults in Hungary. METHODS: In our cross-sectional online study, participants were 18-35 years old (N = 820, 40% male). MEASURES: self-reported anthropometric data, Beliefs About Attractiveness Scale-Revised, Eating Disorder Inventory, SCOFF questionnaire, Sociocultural Attitudes Towards Appearance Questionnaire-3, and Rosenberg Self esteem Scale. RESULTS: The exploratory factor analysis showed that the fit indices of the three-factor solution are acceptable (chi2(171)) = 5124.8, p < 0.001, CFI = 0.944, TLI = 0.918, RMSEA = 0.054, SRMR = 0.030). Along the original 'Importance of being thin' and the 'Importance of being fit' factors, a third factor emerged, namely the 'Life fulfilment aspect of attractiveness' factor. Internal consistency and construct validity of the scales were confirmed. Among those who were at risk of developing an eating disorder, all of the measured beliefs were significantly greater than among those who were not at risk (thin: Z = 6.501, p < 0.001, Cohen's d = 0.63, fit: t(818) = -4.749, p < 0.001, Cohen's d = 0.41, and life fulfilment: t(239) = -5.702, p < 0.001, Cohen's d = 0.53). CONCLUSION: The Hungarian version of the Beliefs About Attractiveness Scale Revised is a reliable, valid measure and we suggest its introduction into Hungarian research. Relationships between beliefs about attractiveness and self- esteem, body image and eating disorders suggest intervention opportunities in with regards to prevention and treatment of eating disorders. PMID- 27188003 TI - [INDIVIDUAL EVALUATION OF LORETA ABNORMALITIES IN IDIOPATHIC GENERALIZED EPILEPSY]. AB - BACKGROUND: Contemporary neuroimaging methods disclosed structural and functional cerebral abnormalities in idiopathic generalized epilepsies (IGEs). However, individual electrical (EEG) abnormalities have not been evaluated yet in IGE patients. METHODS: IGE patients were investigated in the drug-free condition and after 3-6 month of antiepileptic treatment. To estimate the reproducibility of qEEG variables a retrospective recruited cohort of IGE patients was investigated. 19-channel resting state EEG activity was recorded. For each patient a total of 2 minutes EEG activity was analyzed by LORETA (Low Resolution Electromagnetic Tomography). Raw LORETA values were Z-transformed and projected to a MRI template. Z-values outside within the [+3Z] to [-3Z] range were labelled as statistically abnormal. RESULTS: 1. In drug-free condition, 41-50% of IGE patients showed abnormal LORETA values. 2. Abnormal LORETA findings showed great inter-individual variability. 3. Most abnormal LORETA-findings were symmetrical. 4. Most maximum Z-values were localized to frontal or temporal cortex. 5. Succesfull treatment was mostly coupled with disappearence of LORETA-abnormality, persistent seizures were accompanied by persistent LORETA abnormality. DISCUSSION: 1. LORETA abnormalities detected in the untreated condition reflect seizure-generating property of the cortex in IGE patients. 2. Maximum LORETA-Z abnormalities were topographically congruent with structural abnormalities reported by other research groups. 3. LORETA might help to investigate drug effects at the whole-brain level. PMID- 27188004 TI - [COMPUTED TOMOGRAPHIC EXAMINATION OF CRANIAL LESIONS, A PALEORADIOLOGICAL APPROACH]. AB - BACKGROUND AND PURPOSE: Introducing the multidisciplinary paleoradiology research at the Institute of Diagnostic Imaging and Radiation Oncology of the Kaposvar University, highlighting the cases with potential central nervous system involvement--from the scanning methods to the 3D printing--in order to draw attention to the historical background and clinical aspects of certain pathological conditions. METHODS: The authors developed the examination protocols for three different CT scanners. Among the examined archaeological remains cranial lesions were identified in 26 cases, from which 4 cases with potential central nervous system involvement are demonstrated. The scanning parameters and the advantages of secondary image reconstructions (multiplanar reconstruction, maximum intensity projection, three-dimensional volume rendering technique) are presented with the cases. RESULTS: The authors demonstrate a case with destructive skull lesions due to syphilis from the 15th century AD, a condition rarely seen or even unknown nowadays in the modern world. With the CT images of the skull base fracture from the Iron Age, signs of healing could be verified. Using the CT images a non-invasive approach is presented in the case of the craniofacial osteosarcoma in order to visualize the local status and the direct intracranial propagation. Advantages of the 3D VRT reconstructions are shown in the case of unilateral coronal suture synostosis. CONCLUSION: Paleoradiological CT examinations serve as a non-invasive, non-destructive tool for studying archaeological remains and artifacts. The special applications provided by the imaging modality contribute to the conventional paleopathological investigations. PMID- 27188005 TI - SYSTEMIC THROMBOLYSIS AND ENDOVASCULAR INTERVENTION IN POSTPARTUM STROKE. AB - INTRODUCTION: There are no previously published cases about intravenously applied recombinant tissue plasminogen activator in acute ischemic stroke during puerperium. CASE PRESENTATION: We report a 40-year-old woman with postpartum acute ischemic stroke caused by multiple cervical artery dissections treated by systemic thrombolysis and endovascular intervention. DISCUSSION: There are only limited data regarding thrombolytic treatment in acute stroke during pregnancy and puerperium. Current acute stroke treatment guidelines--while considering pregnancy as a relative exclusion criterion--do not deal with the postpartum state. CONCLUSION: As the condition is rare, randomized controlled trials are not feasible, therefore further reports on similar cases could eventually help us suggest guidelines or at least propose recommendations for the acute thrombolytic treatment of strokes occurring in pregnancy and puerperium. PMID- 27188006 TI - [ENDOSCOPIC REMOVAL OF TUBERCULUM SELLAE MENINGEOMA THROUGH ENDONASAL TRANSSPHENOIDAL APPROACH]. AB - Experiences acquired in our department with endoscope assisted microsurgical transsphenoidal pituitary surgery encouraged us to expanded the endoscopic approach to skull base lesions. The endoscopic endonasal transsphenoidal approach proved to be less traumatic to the traditional microsurgical approaches, yet very effective. The endoscopic transsphenoidal technique was applied in a patient havin anterior skull base tumor. The patient was a 49-year-old woman with several months history of left visual defect. The magnetic resonance (MR) scans of the skull revealed a midline anterior fossa space-occupying lesion measuring 21 x 16 x 22 mm located on planum sphenoidale, tuberculum sellae and intrasellar. The tumor compressed both optic nerves and optic chiasm. Total resection of the tumor was achieved by use of endoscopic transnasal, transsphenoidal technique. This is the first reported case of an anterior fossa meningeoma being treated by an endoscopic transsphenoidal technique in Hungary. PMID- 27188008 TI - President's Perspective. PMID- 27188007 TI - [ANTECEDENTS TO THE COMMENCEMENT AND HISTORY OF THE WEST-PANNONIC NEUROLOGICAL FORUM]. AB - INTRODUCTION: Numerous professional groups and sections for the medical specialities have been organized since 1953 in the West-Transdanubian region of Hungary, but such association of neurologists had not occured. ESTABLISHING THE WEST-PANNONIC NEUROLOGICAL FORUM: The lack of regional collaboration among neurologists was related to several factors, among which the most important factor was the lack of a regional medical university, which could coordinate the professional activities. This severe gap necessitated in 1998 the organization of a professional group, that has become a driver for case-consulting conferences and different postgraduate trainings for the physicians specialized in neurology, neurosurgery and neurorehabilitation in counties of Gyor-Moson-Sopron, Vas, Veszpr6m and Zala. THE FUNCTIONING OF THE FORUM: Meetings are organized twice a year for physicians and paramedical staff (nurses, hospital attendants, physiotherapists) on Thursdays afternoons in different towns of the region, in two sections. The lectures are followed by a buffet, after which everyone can get home before too late. Ocasionally guest-lecturers are invited to present scientific topics from Hungarian universities or abroad. However, the main form of the presentations is defined as case discussion. CONCLUSIONS: The numbers of platform and other presentations in the physicians's section have exceeded half a thousand, while in the paramedical section reached the three- hundreds. At the 38. meeting of the Forum in January of this year, the number of participants was more than two-hundreds, reflecting that both physicians and their coworkers are greatly interested in this form of interactions. PMID- 27188009 TI - Peripheral Giant Cell Granuloma. PMID- 27188010 TI - Splint Therapy is the Most Conservative Treatment for Idiopathic Condylar Resorption (UT CAT #2986). PMID- 27188011 TI - Enamel-Caries Prevention Using Two Applications of Fluoride-Laser Sequence. AB - Studies demonstrated a significant synergism between fluoride and laser in reduction of enamel solubility. However, minimal research has focused on testing the sequence of their application and no other research investigated the preventive effect of repeated applications of a combined treatment. This study investigated the effect of two applications of fluoride-laser sequence on the resistance of sound enamel to cariogenic challenge compared to one-time application. Sixty enamel slabs were cut from 10 human incisors, ground flat, polished and coated with nail varnish except a 2 x 2 mm window. Specimens were randomly assigned into five groups of 12 specimens; (CON-) negative-control received no treatment, (CON+) positive-control received pH challenge, (FV) treated with M fluoride varnish, (F-L1) one-application fluoride-varnish followed by CO2 laser-treatment (short-pulsed 10.6 um, 2.4J/ cm2, 10HZ, 10sec), and (F-L2) two-applications of fluoride varnish-laser treatment. Specimens were left in distilled water for one day between applications. Except CON-, all groups were submitted to pH cycling for 9-days (8 demin/ remin + 1 day remineralisation bath) at 37 degrees C. Enamel demineralization was quantitatively evaluated by measurement of Knoop surface-microhardness (SM H) (50-grams/10 seconds). Data were analyzed using one-way ANOVA (p <= 0.05) followed by Duncan's Multiple Range Test. Within the limitations of this study, it was found that one or two applications of fluoride-laser sequence significantly improved resistance of the sound enamel surface to acid attack compared to FV-treated group. Although the two applications of fluoride-laser sequence (F-L1 and F-L2) showed higher SMH values, significant resistance to demineralization was only obtained with repeated applications. PMID- 27188012 TI - Financial Report of the Texas Dental Association: The 2017 Budget. PMID- 27188013 TI - WHY YOU SHOULD PROVIDE VIEWS of Nature at Your Practice. PMID- 27188014 TI - Red, White and Blue; What Does it Mean to You? PMID- 27188015 TI - MINORITY UNDERGRADUATE NURSING STUDENT SUCCESS. AB - BACKGROUND: Minority providers are more likely to practice in underserved areas with minority populations. Currently the representation of minorities in healthcare professions is less than that of the United States population. More research is needed to examine specific variables associated with educational success of minority students. PURPOSE: The purpose of this study is to examine, and increase the understanding of, current factors that influence success among ethnic and minority nursing students. METHODS: The revised Minority Student Nurse Questionnaire (MSNQ) was utilized for this study with a sample of 31 students from 2 entry-level nursing programs in the Midwest. RESULTS: Minority students were slightly older than traditional college students and consisted of African American Black, Native (American) Indian, Asian, Hispanic/Latino, and Hawaiian. Students reported multiple factors that influenced their higher education experience. Academic services and cultural organizations were available, free, but were used by less than half of the students. Several sources of financial assistance are important, including scholarships, federal subsidized and unsubsidized loans, and grants. Students most strongly disagreed with the statement that 'the number of minorities in this program is representative of the number of minorities overall.' Students felt that several services were supportive and helpful strategies for success. CONCLUSION: Although progress has been made to improve success of minority students, numbers continue to lag between demographic population overall. PMID- 27188016 TI - KOREAN AMERICAN PARENTS' PERCEPTIONS OF EFFECTIVE PARENTING STRATEGIES IN THE UNITED STATES. AB - This study aimed to explore the perceptions of Korean American parents on effective parenting strategies taught in a standardized U.S. parenting program. Participants in the study were interviewed using semi-structured open-ended questions, and audio taped interview data were transcribed and analyzed using content analysis. Themes that emerged were: effective parenting strategies, impact of learning effective parenting strategies on parents, and learning effective parenting strategies: impact on children. Findings indicated that Korean American parents felt the program was based on Western parenting strategies but they were effective. They also believed the program strategies would be useful in regulating their emotions, increasing their abilities to be patient and consistent with their children, and helping them explore issues from their child's perspective, all of which they believed improved their parenting self-efficacy and intimacy with their children. Additionally, parents reported that their children acquired more self-confidence, better self-expression, increased obedience and decreased misbehaviors, and increased emotion regulation and problem solving as a result of their participation in the program. These findings could contribute to develop an effective, culturally and linguistically relevant parenting program for Korean American parents. PMID- 27188017 TI - COLORECTAL CANCER SCREENING PRACTICES AMONG THREE AMERICAN INDIAN COMMUNITIES IN MINNESOTA. AB - Colorectal cancer (CRC) is a leading cause of cancer morbidity and mortality. Effective prevention and early detection may be achieved through screening, but screening rates are low, especially in American Indian (AI) populations. We wanted to understand perceptions of CRC screening among AI located in the Great Lakes region. Focus groups were recorded and transcribed verbatim (N = 45). Data were analyzed using qualitative text analysis. Themes that deterred CRC screening were low CRC knowledge, fear of the procedure and results, cost and transportation issues, and a lack of quality and competent care. Suggestions for improvement included outreach efforts and culturally-tailored teaching materials. PMID- 27188018 TI - INFLUENCE OF INTERNATIONAL SERVICE LEARNING ON NURSING STUDENTS' SELF EFFICACY TOWARDS CULTURAL COMPETENCE. AB - One method of gaining knowledge, skills and experience with different cultures for nurses and nursing students is through an international immersion experience with training in language, culture and community nursing. This study is a qualitative and quantitative measurement of the influence of a two-week service learning medical experience on a student-nursing group who traveled abroad to Belize, Central America. PMID- 27188020 TI - Diagnosing androgen deficiency in adult men. PMID- 27188019 TI - BRONX HEALTH EDUCATION PROJECT FOR WEST AFRICAN IMMIGRANTS. AB - BACKGROUND: The transition from a traditional West African diet and lifestyle to a modern diet has a significant impact on health and the risk of chronic disease. OBJECTIVE: To implement a health education program for West African immigrants in the U.S. to address health risks associated with the modern diet. METHODS: A health education program model targeted at West African immigrants in the Bronx was determined based on existing health education programs with educational materials, group education sessions, and targeted individual counseling. RESULTS: A health education program was successfully implemented at a clinic comprised of West African immigrant patients in the Bronx. CONCLUSION: This project demonstrates an example of a targeted health education program for West African immigrants to address health risks related to diet. PMID- 27188021 TI - mRNA-based hrHPV assay in cotesting for cervical cancer screening. PMID- 27188022 TI - Emerging applications in clinical mass spectrometry. PMID- 27188024 TI - Solving the thrombocytopenia puzzle with immature platelet testing. PMID- 27188023 TI - Sentara Laboratory Services: MLO's 2016 Lab of the Year. PMID- 27188025 TI - CDC's more restrictive policy on child lead testing means more positives and high QC. PMID- 27188026 TI - The laboratory's role in the transformation to patient-centered care. PMID- 27188027 TI - In pursuit of patient-centered care. PMID- 27188028 TI - A "fifth generation" HIV assay? PMID- 27188029 TI - Author's response. PMID- 27188030 TI - Genomic Research with Organs and Tissues Originating from Transplant Donors: Ethical Considerations for the GTEx Project. PMID- 27188031 TI - The Optimistic Bias and Illusions of Control in Clinical Research. PMID- 27188032 TI - Who's Willing? Characteristics Associated with Willingness to Participate in Clinical Research. PMID- 27188033 TI - The contemporary landscape of journal publishing. PMID- 27188034 TI - The role of a sexual health promotion leaflet for 15-18 year olds in catalysing conversations: A constructivist grounded theory. AB - Following the summer holidays of 2011, twelve girls returned to school pregnant in one high school in Auckland New Zealand (NZ). A health promotion leaflet that folded into.a small square containing a condom and was dubbed the 'teabag' was distributed to 15-18 year olds prior to the summer holiday of 2012, in order to increase their sexual health knowledge. This paper reports on the evaluation of the teabag from the students' perspective. During the first term of 2013, seventeen students from two high schools who had received the teabag were interviewed. Five were male and twelve female. Most (16) were of Pacific Island or Maori (indigenous New Zealanders) descent. Interviews were digitally recorded, transcribed, coded and categorised concurrently, in accordance with grounded theory methods. Theoretical sampling was employed and students who had perceptions of the teabag, that were consistent with evolving constructions from data, were invited by school nurses to be interviewed by the researchers. Interviews were coded line by line by two researchers and these codes collapsed into seven focussed codes. Further analysis resulted in the codes being subsumed into three main categories. These categories revealed that the teabag was, helpful, appropriate and became a talking point. The grounded theory and basic social process the researchers constructed from data were that the teabag catalysed conversations about sexual health. The teabag was an acceptable and appropriate sexual health promotion tool to disseminate information about sexual health. PMID- 27188035 TI - Supporting palliative care clients who live alone: Nurses' perspectives on improving quality of care. AB - BACKGROUND: Terminally ilL people who live alone at home are disadvantaged in terms of their places of care and death and health outcomes. There is a need to trial models of care that can extend the period of care at home for as long as possible for this group. The objective was to explore the experiences of nurses providing care to terminally ill clients who live at home alone and who were receiving either additional care aide support or a personal alarm through an RCT. METHODS: Nine nurses in a home-based palliative care service in Western Australia completed a questionnaire (82% response rate). FINDINGS: Client willingness to accept additional support from care aides, development of rapport between the client and care staff, and willingness to use the alarm appropriately all influenced the effectiveness of the models of care. These models of care may negate the need for frequent nurses' visits when nurses feeL confident that the care aide can pass on relevant information or that the client will use the alarm when required. CONCLUSIONS: Both models of care assisted in meeting the challenges to care provision; however, further larger trials are needed to test whether these might translate into granting clients their wishes regarding places of terminal care and death. This study is the first account of nurses' perspectives on service provision to support palliative care clients who live alone. It has prompted changes in practice and will inform service planning for this growing and challenging population group. PMID- 27188036 TI - Strengthening the capacity of nursing leaders through multifaceted professional development initiatives: A mixed method evaluation of the 'Take The Lead' program. AB - BACKGROUND: Effective nursing leadership is necessary for the delivery of safe, high quality healthcare. Yet experience and research tells us that nursing leaders are commonly unprepared for their roles. Take The Lead (TTL), a large scale, multifaceted professional development program was initiated in New South Wales, Australia, to strengthen the capacity of Nursing/Midwifery Unit Managers (N/MUMs). The aim of this study was to examine the effects of TTL on job performance, nursing leadership and patient experience. METHODS: Nursing/Midwifery Unit Managers (n = 30) and managers of N/MUMs (n = 30) who had completed the TTL program were interviewed between August and December 2010. The semi-structured interviews included a combination of open-ended questions and questions that required respondents to rate statements using a Likert scale. Data from the open-ended questions were thematically analysed to identify and categorise key concepts. The responses to the Likert items were analysed via descriptive statistics. RESULTS: Nursing/Midwifery Unit Managers' participation in TTL engendered improvements in job performance and leadership skills, as well as some improvement in patients' experiences of care. The program facilitated role clarification and helped foster peer-support and learning networks, which were perceived to provide ongoing professional and personal benefits to participants. CONCLUSIONS: Our study revealed a consensus about the beneficial outcomes of TTL among those involved with the program. It supports the significant and ongoing value of widely implemented, multifaceted nursing leadership development programs and demonstrates that participants value their informal interactions as highly as they do the formal content. These findings have implications for delivery mode of similar professional development programs. PMID- 27188037 TI - Evidence based nursing and midwifery practice in a regional Australian healthcare setting: Behaviours, skills and barriers. AB - AIM: To establish self-reported skill levels, behaviours and barriers in relation to evidence-based practice (EBP) among a representative sample of regional Australian nurses and midwives in senior roles. BACKGROUND: It has been widely established that nurses and midwives continue to face challenges in relation to putting evidence into practice on the clinical floor. Prior to conducting an EBP capacity building activity in a regional Australian Local Health District, a survey assessing needs and skill and barrier areas was conducted. METHODS: A quantitative descriptive survey which utilised the 'Developing Evidence Based Practice Questionnaire' (DEBPQ) was conducted in early 2012 among senior nurses and midwives of a regional New South Wales Local Health District (LHD). The survey results were contrasted with reported DEBPQ results from a sample of UK metropolitan nurses and a sample of Australian general practice nurses (GPNs). RESULTS: One hundred and sixty nine nurses completed the survey (response rate 42%). Survey respondents' reliance on accepted evidentiary knowledge sources was found to be low. Research literature-related knowledge sources were ranked outside of the top 10 sources, compared with numerous personalised and subjective sources, which ranked within the top 10. Access to and understanding of research material was a primary barrier to reviewing evidence in the study sample. Time related barriers to changing practice on the basis of evidence figured prominently in the study sample and the UK and Australian GPN samples. The study sample rated their EBP skill levels significantly higher than both their UK counterparts and the Australian GPN sample (P < 0.0001). CONCLUSION: Capacity building interventions are needed among senior nurses and midwives in Australian regional LHDs, as the most prominent knowledge sources reported are non evidentiary in nature and barriers to finding and reviewing evidence, along with barriers to making practice change, remain significant. PMID- 27188038 TI - Development and psychometric evaluation of an instrument for the assessment of nurses' knowledge on capnography. AB - BACKGROUND: Despite the expansion of capnography use, instruments for evaluating healthcare professionals' knowledge about capnography are missing from international literature. OBJECTIVES: To develop and validate an instrument for evaluating nurses' knowledge about capnography, named the "Nurses' Knowledge about Capnography Test" (NKCT). METHOD: A literature review was performed to formulate instrument items. Thirty-six items were initially developed, which covered principles of capnography function, conditions affecting end-tidal CO2 pressure and capnography waveform, and indications for capnography use. Six items were deleted after content validity and intra-rater reliability evaluation. The final 30-item instrument was completed by 103 anesthesiology department nurses employed in six hospitals of Greece, to test its internal consistency, item difficulty and discrimination, and construct validity. RESULTS: Kuder-Richardson 20 coefficient was 0.79. Ten items were found to be of high difficulty, while item discrimination was low for two of them. Instrument scores were found significantly higher among participants with higher educational level and longer experience in capnography use. CONCLUSION: NKCT is a psychometrically comprehensive instrument for evaluating nurses' knowledge about capnography, which is recommended to be re-validated beyond the anesthesiology department and be used for the assessment of educational programs on capnography. PMID- 27188039 TI - Some strategies to address the challenges of collecting observational data in a busy clinical environment. AB - Studies drawing on observational methods can provide vital data to enhance healthcare. However, collecting observational data in clinical settings is replete with challenges, particularly where multiple data-collecting observers are used. Observers collecting data require shared understanding and training to ensure data quality, and particularly, to confirm accurate and consistent identification, discrimination and recording of data. The aim of this paper is to describe strategies for preparing and supporting multiple researchers tasked with collecting observational data in a busy, and often unpredictable, hospital environment. We hope our insights might assist future researchers undertaking research in similar settings. PMID- 27188040 TI - Effects of an integrated simulation-based resuscitation skills training with clinical practicum on mastery learning and self-efficacy in nursing students. AB - BACKGROUND: This study evaluates the effectiveness of integrated simulation-based resuscitation skills training combined with a clinical practicum by assessing nursing students' knowledge, psychomotor skills, and self-efficacy. METHODS: In a pretest-posttest design, 255 second-year nursing students participated in an emergency nursing clinical course consisting of a two-hour simulation-based resuscitation skills training component along with an 80-hour clinical placement in an emergency department. Knowledge, self-efficacy, and psychomotor skill errors were measured. Analyses of pre- and post-test data were performed on three subgroups: the simulation-only group, the simulation with clinical observation group, and the simulation with clinical performance group. Stu- dents were divided into these groups based on resuscitation experiences during their clinical practicum in the emergency department. RESULTS: Mean scores of knowledge (z = -13.879, p < .001) and self-efficacy (z = -10.969, p < .001) significantly improved after the clinical practicum compared to baseline. Knowl- edge (F = .502, p = .606), psychomotor skill error (F = 1.587, p = .207), and self-efficacy (F = .481, p = .619) did not significantly differ among the three subgroups after controlling for two covari- ates (age, Basic Life Support certification) in the analysis of covariance models. CONCLUSION: Integrated simulation-based resuscitation skills training combined with a clinical practicum might be beneficial for enhancing mastery learning and self-efficacy in nursing students through learner engagement and feedback. PMID- 27188041 TI - Readmission rates and related factors in heart failure patients: A study in Lebanon. AB - BACKGROUND: Heart failure is the leading cause of hospitalization among older adults in the United States and other developed countries. Readmission rates of heart failure patients is one of the key outcome performance measures used in evaluating the quality of care of these patients. In Lebanon, there are no published data on readmission of heart failure patients. The aim of the study was to examine the readmission rates of heart failure patients within 30, 60 and 90 days of discharge from the hospital, and factors associated with readmission. METHODS: The medical records of all 187 patients admitted with heart failure to Rafic Hariri University Hospital in Beirut between January 1, 2010 and December 31, 2010 were reviewed. Data on demographic and relevant clinical variables were retrieved. RESULTS: Readmission rates were 15%, 22.2%, and 27.8% at 30, 60 and 90 days following discharge, respectively. The majority of readmissions (73.61%) were due to heart failure exacerbations. Significant predictors of readmission were: history of diabetes mellitus, coronary artery disease, length of stay at the index admission and gamma glutamyl transpeptidase levels. Management of the patients did not always conform to the evidence based guidelines. CONCLUSION: The findings suggest the need for better adherence to clinical guidelines in caring for heart failure patients and improved documentation of discharge instructions. PMID- 27188042 TI - How has the profile of Australian nurse practitioners changed over time? AB - AIM: To examine longitudinal changes in the profile of Australian nurse practitioners surveyed in both 2007 and 2009 ('resurveyed respondents') and to determine differences between nurse practitioners who completed the census only in 2009 ('new respondents') and resurveyed respondents. BACKGROUND: The nurse practitioner role is integral to the development and sustainability of advanced practice roles in healthcare systems. However, its success depends upon support from policy makers, health services and nursing. A census of Australian nurse practitioners previously was conducted in 2007 to obtain national data on the role and scope of practice of nurse practitioners in Australia. DESIGN: A quantitative self-administered survey. METHODS: Questionnaires were sent to all authorised Australian nurse practitioners in 2009. RESULTS/FINDINGS: A total of 408 surveys were administered with 293 questionnaires completed (response rate 76.3%). Of these, 49% of participants also had completed the 2007 survey. There were no differences in the limitations and enablers identified in 2007 compared to 2009, indicating that perceived barriers had not been addressed over time, nor had there been substantial improvements. New respondents were more likely to have worked as a nurse practitioner in the previous week (p < 0.004). There was a significant increase in the number of nurse practitioners waiting on approval for some or all clinical protocols (p = 0.024). CONCLUSIONS: Conditions enabling work to full scope of practice continue to be perceived as suboptimal by Australian nurse practitioners. Supportive strategies are needed to enable the role to be effectively utilised. PMID- 27188043 TI - "Will I come home incontinent?" A retrospective file review: Incidence of development of incontinence and correlation with length of stay in acute settings for people with dementia or cognitive impairment aged 65 years and over. AB - AIM: The aim of the retrospective file review is to obtain incidence of the development of incontinence at time of discharge from an acute/sub-acute care setting for patients who were aged 65 years and over, diagnosed with dementia or cognitive impairment, ambulant and continent pre-admission. Along with, identifying correlation between length of stay and development of incontinence. The data were obtained to measure a need for recommendations related to continence promotion in hospitals. It is hypothesised that the sample group are at risk of developing incontinence throughout their stay. METHOD: Files for the sample group who were admitted to a regional Victorian hospital acute/sub-acute care over a two-year period were reviewed. A total of 182 files were reviewed, of which 100 files met the inclusion criteria. RESULTS: The study revealed a significant relationship between admission and the development of incontinence for the sample group (p = .007). At time of discharge from the hospital, 36% suffered urinary incontinence. Of the 36%, 2% also developed new faecal incontinence at time of discharge. A further 21% of patients also experienced an episode of urinary incontinence throughout their stay, but were continent at discharge. An independent-sample t-test was conducted to compare mean length of stay between the group that remained continent (M = 15.88, SD = 13.028) and the group that developed incontinence (M = 24.33, SD = 19.497); t(98) = 2.586, p = .011 (two-tailed). CONCLUSION: Statistically significant results confirm the hypothesis' that the; sample group are at significant risk of developing incontinence throughout a hospital admission, and increased length of stay increases the likelihood of developing a form of incontinence. PMID- 27188044 TI - Why nurses chose to remain in the workforce: Portraits of resilience. AB - AIM: This study explored why nurses chose to remain in the Western Australian workforce and to develop insights into the role of resilience of nurses and to identify the key characteristics of resilience displayed by these nurses. BACKGROUND: Nursing is a stressful profession. Prolific quantitative research which measures job stress and resilience has been implemented; however, there is a dearth of qualitative studies which hear the personal narratives as to why nurses remain and thrive in a stressful workplace. DESIGN/METHODS: Vignettes of nursing resilience reveal underlying themes of resilience where personal stories and events are presented as narrative. Portraiture recognises the inherent value of the nurses' stories giving attention to the nature of their resilience. Interpretation illuminates the portraits or verbal canvasses of the told experience, reflecting success and positivity despite disarray in healthcare settings. RESULTS/FINDINGS: Eight themes were identified. The portraits highlight a sometimes imperceptible theme of resilience within nursing. Nurses are resilient; they rely on the social support of colleagues, family and friends to continue to bear their mantle of responsibility. They take pride in their work and accomplishments and give to others altruistically. They laugh, they love nursing and they keep the needs of their patients, clients, residents or students foremost. CONCLUSION: This paper describes the hallmarks of resilience demonstrated by nurses. Resilience and its relationship to coping in times of adversity are captured within the portraits presented. PMID- 27188046 TI - Educational and intervention programmes for gestational diabetes mellitus (GDM) management: An integrative review. AB - INTRODUCTION: Gestational diabetes mellitus (GDM) is a serious pregnancy disorder, which is linked to stillbirth, birth damage and later development of type 2 diabetes. Rates of GDM have increased dramatically in the past 20 years, related to obesity, sedentary lifestyles and ethnicity. AIM: The aim of this integrative review was to identify and to critically review existing self management programmes for GDM. METHOD: A search for studies published between 2000 and 2013 was conducted on: PubMed, CINAHL, Medline, OvidSP, ProQuest, SCOPUS and Wiley online library. GDM search terms included gestational diabetes mellitus; GDM, pregnancy diabetes. Search terms for self-management programmes, included educational programmes; lifestyle intervention; exercise, diet, weight management in pregnancy; life-style interventions. RESULTS: Fifty papers were located in the search, and 12 were included in the review. Interventions fell into three main groups: (1) dietary and exercise interventions; (2) self monitoring of blood glucose levels; and (3) counselling/behavioural interventions. This review found that although interventions varied in approach, most were successful in reducing insulin requirements; in reducing rates of macrosomia and hypertensive disorders, and in improving levels of knowledge and pregnancy outcomes. Only one study found that the intervention did not contribute some positive outcome. CONCLUSION: Interventions that include adopting a low glycemic index diet and increasing levels of activity appear to be successful at reducing maternal blood glucose levels and reducing insulin requirements during pregnancy. Reducing maternal blood glucose levels, in turn, is associated with a reduction of macrosomia and maternal weight gain. PMID- 27188045 TI - Recognising falls risk in older adult mental health patients and acknowledging the difference from the general older adult population. AB - Older adults admitted to inpatient mental health units present with complex mental health care needs which are often compounded by the challenges of living with physical co-morbidities. They are a mobile population and a high risk group for falling during hospitalisation. To address quality and safety concerns around the increased risk for falls, a qualitative research study was completed to obtain an improved understanding of the factors that increase the risk of falling in this patient cohort. Focus groups were conducted with mental health professionals working across older adult mental health services in metropolitan Western Australia. Data were analysed using content analysis and three themes emerged that were significant concepts relevant to falls risk in this patient group. These themes were (1) limitations of using generic falls risk assessment and management tools, (2) assessment of falls risk not currently captured on standardised tools, and (3) population specific causes of falls. The findings demonstrate that older adult mental health patients are a highly mobile group that experience frequent changes in cognition, behaviour and mental state. The mix of patients with organic or functional psychiatric disorders within the same environment also presents complex and unique care challenges and multi disciplinary collaboration is central to reduce the risk of falls. As this group of patients are also frequently admitted to both general inpatient and aged care settings, the findings are relevant to the assessment and management of falls risk across all health care settings. PMID- 27188047 TI - Pre-registration paid employment practices of undergraduate nursing students: A scoping review. AB - OBJECTIVES: This article presents findings from a scoping review that sought to highlight what is known about pre-registration paid employment practices of undergraduate nursing students. BACKGROUND: Researchers have identified large numbers of undergraduate nursing students engaging in paid employment. This review was prompted by our interest in the different employment choices that students make and whether these choices have any impact on transition to practice. DESIGN: A scoping review was designed to map the existing evidence base on undergraduate student nurse employment practices. Scoping reviews support the identification of a broad range of literature, which encompasses all types of study design. DATA SOURCES: Utilising key search terms, databases searched included MEDLINE, CINAHL, Psych INFO, EMBASE, SCOPUS, SCIRUS, Joanna Briggs Institute, Web of Science, Informit Health and the Cochrane database. REVIEW METHOD: We utilised Arksey and O'Malley's five-stage approach: identifying the research question; identifying relevant studies; study selection; charting the data; and collating, summarising and reporting the results. Based on the research question, relevant literature was selected which was reported in accordance with Arksey and O'Malley's framework. RESULTS: The scoping review identified 40 articles that explored the nature of undergraduate student nurse paid employment activity. Highlighted themes included: reasons for engaging in paid employment; specific paid employment models; paid employment and academic performance, and paid employment choice and transition to graduate practice. CONCLUSION: The review highlighted a lack of studies detailing the relationship between paid employment and transition to graduate nurse practice, particularly those studies situated within the hospitality sector. PMID- 27188048 TI - The complexities of defining nurse practitioner scope of practice in the Australian context. AB - AIMS: To explore the legislative and regulatory constraints that defines nurse practitioner scope of practice within the Australian context. BACKGROUND: Nurse practitioners have been endorsed to practice in Australia for over 13 years. However, despite this lengthy period, there still remains confusion amongst newly endorsed nurse practitioners and their employers as to what determines the scope of their practice in Australia. DESIGN: A review of available policy and regulatory documents related to the Australian operational requirements for nurse practitioner scope of practice cited within or referred to by the Nursing and Midwifery Board of Australia. DATA SOURCES: Data were collected over a 2-month period in 2013. This utilized the current standards, codes and guidelines cited by the Nursing and Midwifery Board of Australia related to scope of practice and nurse practitioner, as well as legislation and regulation referred to in relation to nurse practitioner practice. Information was also obtained through government health and professional organization websites. All information in the literature regarding current and past status, and nomenclature of advanced practice nursing was considered relevant. Implications for nursing: Providing a means of interpreting the determinants of nurse practitioner scope of practice within Australia. CONCLUSIONS: The factors that determine nurse practitioner scope of practice, education, clinical experience, and competence leading to endorsement, are straightforward. However, the context of clinical practice, including jurisdictional restrictions, is major barriers to the expression of nurse practitioner scope of practice. These restrictions, although not insurmountable, continue to hinder nurse practitioners from practicing to their full scope of practice. PMID- 27188049 TI - [Not Available]. PMID- 27188050 TI - [The Lausanne Obesity Cohort: why and how?]. AB - Bariatric surgery has become the treatment of choice for severe obesity. The significant weight loss induced by these procedures is accompanied by spectacular improvements in the metabolic comorbidities that participate in morbidity and mortality of obesity. However, several questions remain open regarding the identification of patients that will benefit the most from the intervention or the long-term outcomes in terms of weight and co-morbidities. The Cohort obesity of Lausanne was initiated in order to try and answer some of these questions, and more specifically to identify predictive factors of long-term response to gastric by-pass. PMID- 27188051 TI - [How to support obese patients in a long-term process of change?]. AB - It is illusory to think losing weight effectively by acting only on diet or physical activity. To lose weight satisfactorily and to maintain that weight loss, we should move more on lifestyle changes, namely changes in behavior on several axes. Through concrete examples of an obese patient wanting to lose weight, we will see what skills he must acquire to achieve its objective and what tools the therapist can use to help. PMID- 27188052 TI - [A tool for assessing eating behaviors: ESSCA]. AB - Eating behaviors are key when considering overweight or obesity management. Many issues varying in severity can interfere with the treatment. This article provides a semi-structured interview to address the determinants of food intake- hunger food craving--problematic eating behaviors--snacking, emotional eating- and eating disorders particularly related to overweight. Convenient for healthcare practitioners, this instrument comes with an interview guide to standardize its use. The relatively complete picture of the patient's eating behavior resulting from this assessment contributes to the treatment proposal. PMID- 27188053 TI - [Not all patients might benefit from gastric by-pass]. AB - Obesity is a chronic disease with a need for long-term follow-up. Bariatric surgery is very beneficial for patients who are not able to lose weight by lifestyle modifications alone. However, some patients present a weight regain after surgery. Predictive factors for the evolution of weight loss after bariatric surgery are not available today. For that reason, all preventive and therapeutic facilities should be used in order to reduce the risk of relapse after surgery. A recently introduced multidisciplinary therapeutic program for preparation of patients before bariatric surgery could be very valuable for a sustainable change of their lifestyle in order to minimize the risk of weight regain in the years after surgery. PMID- 27188055 TI - [Pregnancy after bariatric surgery]. AB - Bariatric surgery interventions are rapidly growing and most are performed on female patients. Thus, pregnancies after bariatric surgery are increasingly common. Awareness of the consequences and risks of bariatric surgery on subsequent pregnancies is important. Literature data report a reduction of the usual pregnancy risks of pregnancies in obese patients, but also an increased risk of small-for-gestational-age infants, possibly related to nutritional deficiencies. A careful screening for micronutrient deficiencies is therefore already advised before conception. Nutritional follow-up and serious evaluation of any abdominal complaints are recommended as well during pregnancy. PMID- 27188054 TI - [Increased risk of alcohol use disorders after bariatric surgery]. AB - After bariatric surgery the risk of alcohol use disorders is increased. This risk is greater after Roux-en-Y gastric bypass than after sleeve gastrectomy or gastric banding. These differences can be explained by modification in alcohol metabolism after gastric bypass, which increases peak alcohol levels. Other mechanisms that might be responsible for increased alcohol use disorders after bariatric surgery are neuro-biological contributors and addiction transfer from binge eating to alcohol consumption. Collaboration with a team specialized in alcoholism treatment is needed for the management of such patients. PMID- 27188056 TI - [Prognostic scores for pulmonary embolism]. AB - Nine prognostic scores for pulmonary embolism (PE), based on retrospective and prospective studies, published between 2000 and 2014, have been analyzed and compared. Most of them aim at identifying PE cases with a low risk to validate their ambulatory care. Important differences in the considered outcomes: global mortality, PE-specific mortality, other complications, sizes of low risk groups, exist between these scores. The most popular score appears to be the PESI and its simplified version. Few good quality studies have tested the applicability of these scores to PE outpatient care, although this approach tends to already generalize in the medical practice. PMID- 27188057 TI - [Not Available]. PMID- 27188058 TI - [Not Available]. PMID- 27188059 TI - [Not Available]. PMID- 27188060 TI - [Not Available]. PMID- 27188061 TI - [Not Available]. PMID- 27188062 TI - [Not Available]. PMID- 27188063 TI - [Not Available]. PMID- 27188064 TI - [Not Available]. PMID- 27188065 TI - NEHA Goes to Washington. PMID- 27188067 TI - Assessment of Enterococcus Levels in Recreational Beach Sand Along the Rhode Island Coast. AB - Recent studies have shown that coastal beach sand as well as coastal ocean water can be contaminated with fecal indicator Enterococcus bacteria (ENT). A study of sand ENT concentrations over a four-week period at 12 Rhode Island beaches was conducted during the summer of 2009. While average contamination was low relative to water quality standards, every beach had at least one day with very high sand ENT readings. On 10 of the 12 beaches, a statistically significant gradient occurred in geometric mean ENT concentrations among tidal zones, with dry (supratidal, or above high tide mark) sand having the highest level, followed by wet (intratidal, or below high tide mark) and underwater sand. Beaches with higher wave action had significantly lower ENT levels in wet and underwater sand compared to beaches with lower wave action. PMID- 27188066 TI - Where Are the Ticks? Solving the Mystery of a Tickborne Relapsing Fever Outbreak at a Youth Camp. AB - During the summer of 2014 an outbreak of tickborne relapsing fever (TBRF) occurred in a group of high school students and staff at a youth camp, which was reported to Coconino County Public Health Services District. Six confirmed and five probable cases of TBRF occurred. During the environmental investigation two rodents tested positive for TBRF, but the vector, soft ticks, could not be found in their "normal" habitat. Ticks were finally located in areas not typical for soft ticks. PMID- 27188068 TI - Health and Environmental Hazards of Electronic Waste in India. AB - Technological waste in the form of electronic waste (e-waste) is a threat to all countries. E-waste impacts health and the environment by entering the food chain in the form of chemical toxicants and exposing the population to deleterious chemicals, mainly in the form of polycyclic aromatic hydrocarbons and persistent organic pollutants. This special report tries to trace the environmental and health implications of e-waste in India. The author concludes that detrimental health and environmental consequences are associated with e-waste and the challenge lies in producing affordable electronics with minimum chemical toxicants. PMID- 27188069 TI - Regional Data Standards Build Capacity for Health Departments. PMID- 27188070 TI - A, T, S, D, What? PMID- 27188071 TI - New Emergency Response Training for Environmental Health Professionals. PMID- 27188072 TI - It's a Government Affair. PMID- 27188073 TI - Why bacteria are the basis of breastfeeding. PMID- 27188074 TI - The faces of breastfeeding support: Experiences of mothers seeking breastfeeding support online. AB - The aim of this study was to advance understanding of the experiences of mothers using closed Facebook groups attached to the Australian Breastfeeding Association (ABA) and how these mothers find and share breastfeeding support and information using this forum. The study involved members of three closed Facebook groups that were chosen as interesting cases for study, based on the volume and nature of their posts. Members of these three groups then participated in online depth interviews and online semi-structured focus groups. The overarching theme identified was support, with four sub-themes that describe the nature of online breastfeeding support within the Facebook environment. These sub-themes are: community, complementary, immediate and information. It was found that social networking sites (SNSs) provide support from the trusted community. It is immediate, it complements existing support or services that ABA provides and also provides practical and valuable information for its users. PMID- 27188075 TI - Relationships between assisted reproductive technologies and initiation of lactation: Preliminary observations. AB - OBJECTIVE: This study examined initiation of lactation in primiparous mothers of late preterm infants who had conceived with assisted reproductive technology (ARTC) compared to those who conceived spontaneously (SC). METHOD: Milk productions on day 4 (72-96 hours) and day 7 (144-168 hours) postpartum were measured by weighing expressed breastmilk and test weighing breastfeeds in the ARTC (n = 8) and SC (n = 8) groups. RESULTS: Mean total milk volumes for the ARTC group compared to the SC group were clinically lower on day 4 (191 mL, SD = 110 vs. 285 mL, SD = 225) and on day 7 (374 mL, SD = 238 vs. 601 mL, SD = 243) respectively. CONCLUSION: These preliminary observations indicated milk production in the first week was clinically lower in mothers with ARTC, with a range of potential influencing factors identified, suggesting the need for a higher-powered study investigating the effects of ART on the initiation of lactation. PMID- 27188077 TI - Breastfeeding with cystic fibrosis. PMID- 27188076 TI - Infant-feeding practices and American Indian infants' gut microbiome: Rationale of the pilot study. AB - This study aims to examine the relationship between infant-feeding practices and American Indian infants' gut microbiome--laying the foundation of a research program aimed at identifying potential aetiologies of childhood obesity in this population. Previous studies have emphasised the high prevalence of obesity in American Indian infants, but its underlying causes remain unclear. We received funding from the University of Washington to examine attitudes towards breastfeeding and formula feeding in American Indian mothers, their dietary and physical activity habits and the yield, quality and diversity of their infants' gut microbiome. Our study combines the strengths of qualitative and quantitative data with DNA sequencing. Results will be used to propose a larger study aimed at clarifying aetiologies of childhood obesity in this population and to identify prevention strategies. This protocol describes the theoretical basis of the study, rationale for the target population, study design, participant recruitment and data analysis plan. PMID- 27188079 TI - News from D-DENT. PMID- 27188080 TI - You'll be missed, Dr. Clint Miner. PMID- 27188081 TI - ODA MEMBER Martha Garzon, OKC. PMID- 27188082 TI - CREATIVITY + INGENUITY = TOM MCGINNITY, DMD. PMID- 27188083 TI - Why Schein's $250,000 FTC Fine May Mean HIPAA Liability For You. PMID- 27188085 TI - [Percutaneous treatment of coronary chronic total occlusions]. AB - Chronic total occlusions (CTOs) are frequently detected on diagnostic coronary angiograms. For the selection of patients for CTO percutaneous coronary intervention, factors such as the level of symptoms, level of myocardial viability and extent of ischemia must be taken into account. Remarkable progress has been achieved in the success of complex CTO procedures during the past decade. In addition to antegrade wire escalation strategy, subintimal passage of the guidewire with or without dissection and re-entry techniques and retrograde techniques can be utilized. After successful wiring of the lesion, balloon angioplasty and stenting comparable to a non-CTO lesion are performed. PMID- 27188084 TI - Angioedema of the Uvula: A Case Report. PMID- 27188086 TI - [Male breast cancer]. AB - Breast cancer is rare in men. Diagnosis of the illness may be delayed due to the fact that the doctor and the patient fail to suspect it. Male breast cancer is treated mainly on the same principles as female breast cancer. A man affected with breast cancer should always be directed to genetic testing, as inherited mutations increasing the risk of developing cancer are more common than in female breast cancer. Most breast cancers in men are hormone receptor positive. Among hormone treatments, the antiestrogen tamoxifen exhibits the best efficacy both in early-state and advanced cases. PMID- 27188087 TI - [New psychosocial therapies for schizophrenia]. AB - Almost all schizophrenia patients suffer from various cognitive symptoms that cause difficulties in everyday living and lower the quality of life even when psychotic symptoms are in remission. Defects in social cognition constitute special problems that relate to recognizing facial expressions and understanding social situations, for example. There is no evidence that psychiatric medication improves these symptoms. On the other hand, there are several cognitive remediation programs that have been shown to be of use. New programs have also emerged to treat problems in social cognition. When neurocognitive rehabilitation is insufficient, a program that compensates for deficits in cognitive functioning is also available. PMID- 27188088 TI - [Drug therapy of advanced pancreatic neuroendocrine tumor]. AB - Although several options of drug therapy exist for advanced neuroendocrine cancer of pancreatic origin, few data based on randomized studies are available. The results of the most recent randomized placebo-controlled studies are obscured by the assignment of patients from the placebo branch to the treatment branch. Application of the study results is further hampered by small patient groups, heterogeneity and retrospective set-up of study materials and, in older studies, inaccurate response assessment. We describe drug therapies that can be utilized to affect the clinical course of locally advanced or metastatic neuroendocrine cancer of pancreatic origin. Supportive therapy of hormonally active tumors has been restricted to somatostatin analogue treatment. PMID- 27188089 TI - [Rapid diagnosis of diarrhea viruses]. AB - Viral diagnosis is required mainly in the analysis of outbreaks of diarrhea, cases of gastroenteritis in infants and in the exploration of the cause of diarrhea in severely ill patients. Antigens of rotaviruses and adenoviruses can be detected in the feces of the patient, and the rapid tests applied have proven to possess sufficient sensitivity. Sensitivities of the tests intended for norovirus antigen detection have instead remained poor. In addition to antigen detection tests, a real-time PCR test based on the,detection of norovirus nucleic acids has come onto the market, being both easy to use and substantially more sensitive. In the future, multiplex PCR tests allowing simultaneous detection of several different diarrhea-causing microorganisms are expected to become more common. PMID- 27188090 TI - [Recognize tuberculosis--prevent outbreak]. AB - INTRODUCTION: The number of tuberculosis cases in Finland has decreased. Cases among immigrants have, however, increased, and the disease may not be recognized early enough. METHODS: We describe four group exposures to tuberculosis that occurred in Finland, the index patient coming from a country with a high incidence rate of tuberculosis. RESULTS: Over 900 persons were exposed to tuberculosis. Coordination of the surveys was hampered by the fact that several healthcare operators participated in the study. Three index patients had drug resistant tuberculosis, one of which was multidrug resistant. CONCLUSIONS: Extensive operations of tracking and prevention could have been avoided, if the symptoms would have been recognized earlier. PMID- 27188091 TI - [Sarcoidosis-lymphoma syndrome]. AB - Lymphoma risk is increased in middle-aged patients in association with chronic active sarcoidosis. The sarcoidosis- lymphoma syndrome poses a challenge for differential diagnosis particularly in the era of fluoro-deoxy-glucose positron emission tomography-computed tomography (FDG-PET-TT). Upon detection of enlargement of lymph nodes, the diagnosis should be confirmed with a histological sample. PMID- 27188092 TI - [Thoracic lavage and open cardiac massage as treatment of hypothermic cardiac arrest--case report]. AB - Cardiopulmonary bypass is the treatment of choice for a severely hypothermic patient with cardiac arrest. However, the treatment is not always available. We describe a successful three-and-a-half hour resuscitation of a hypothermic cardiac arrest patient with manual chest compressions followed by open cardiac massage and rewarming with thoracic lavage. PMID- 27188093 TI - [Update on Current Care Guideline: Venous thromboembolism (VTE): deep venous thrombosis and pulmonary embolism]. AB - Key recommendations in management of VTE include prompt and systematic diagnostics based on clinical probability, D-dimer testing and imaging studies, and individualized antithrombotic treatment. Outpatient management is encouraged for patients with favourable prognosis. Interventions such as thrombolysis, venous stenting and inferior vena cava filters are limited to specific subgroups of patients. The duration of anticoagulation is tailored by balancing the risks of VTE recurrence and bleeding. Without contraindications, the minimal duration of anticoagulation is 3 months. The selection between warfarin, direct oral anticoagulants (apixaban, dabigatran, rivaroxaban) and low molecular weight heparin is based on individual patient characteristics and suitability of each drug. PMID- 27188094 TI - Hold Thy Tongue, O Thou Holy Physician.... PMID- 27188095 TI - PRESIDENT'S PAGE. PMID- 27188098 TI - [Welcome Newcomers to Our World!]. PMID- 27188096 TI - Blood Donor Screening for West NiIe Virus in Oklahoma and Its Contribution to Disease Surveillance, 2003 -2013. AB - Upon recognition that West Nile virus (WNV) was transmissible by transfusion, universal testing of blood donors by nucleic acid testing (NAT) was initiated in 2003. A retrospective review of 2003-2013 blood donor records and public health surveillance data in Oklahoma was undertaken to determine the percentage of WNV positive blood donors who developed clinical symptoms post-donation and to examine the incidence and timing of WNV viremic donors in the context of WNV disease reported statewide. Among all WNV NAT-positive blood donors, 19% had self described symptoms consistent with WNV disease. A viremic blood donor was the seasonal index case of WNV transmission in Oklahoma during one year [2006] of the study period. Blood donors remain an important surveillance component for epidemiologic monitoring of WNV in Oklahoma. PMID- 27188097 TI - Consultation Dilemma Catatonia in a Patient with Prior TBI: MentaI or Medical Disorder? AB - Mr. R, a 27 year old Hispanic male with history of traumatic brain injury (TBI) over ten years prior but no psychiatric history, presents to the psychiatric consultation service with recent onset of mutism, psychotic behavior and new diagnosis of epilepsy. The differential diagnosis is broad and includes both medical and psychiatric causes: post-ictal state, non-convulsive status epilepticus, delirium due to metabolic conditions, drugs, catatonia, conversion disorder, major depression with psychotic features, new onset schizophrenia or a combination of these possible diagnoses. We explore different medical causes that can present with symptoms of catatonia, as it is crucial to rule out a possible treatable medical cause. PMID- 27188099 TI - [Sniffing Position and i-gel Rotation Approach for i-gel Insertion under General Anesthesia]. AB - BACKGROUND: Insertion assistance techniques, such as the sniffing position (SP) and i-gel? rotation approach (RA), are recommended in the i-gel supraglottic airway device insertion manual. The usefulness of these techniques was evaluated, in this study, under general anesthesia. METHODS: In 50 adult patients, the i-gel was inserted with the patient in the mild-SP with 5 degrees head extention at first attempt. When resistance was encountered during insertion or airway patency was not obtained after insertion, the i-gel was re-inserted with the patient in the full-SP with maximum head extention during second attempt. When re-insertion failed, the i-gel was inserted with the patient in the full-SP and by using the i gel RA during third attempt. RESULTS: Airway patency was established in the mild SP in 36 of 50 patients, in the full-SP in 11 of the remaining 14, and in the full-SP with the i-gel RA in the remaining 3. The average insertion time was 24.0 s during the first attempt, 22.2 s during the second, and 18.2 s during the third. No major complications were observed. CONCLUSIONS: Both the full-SP and the i-gel RA can be used for i-gel insertion. PMID- 27188100 TI - [Ultrafast-track Anesthesia (UFTA) in the Operating Room and the Anesthetic Management for Off-pump Coronary Artery Bypass (OPCAB)]. AB - Currently, the immediate extubation in the operating room is necessary for the patients undergoing off-pump coronary artery bypass (OPCAB). To achieve UFTA, anesthesiologists should control general anesthesia. We report the case series of UFTA for the patients undergone OPCAB at our hospital. Forty patients receiving OPCAB between April 2012 and April 2014 were retrospectively analyzed. We divided the patients into those extubated in the operating room (Extubation group) and those not (Intubation group). The extubation criteria included adequate revascularization, adequate hemostasis, ratio between Pa(O2) and FI(O2) more than 250, body temperature above 36 degrees C, stable hemodynamics without noradrenaline, without IABP, and normal postoperative chest X-ray. Twenty-three patients (70% of the scheduled and 20% of the emergency patients) were included in our criteria and could be extubated in the operating room. One patient was re intubated due to asthma attack following extubation in the operating room. The sucess rate of immediate extubation was 95.7% by our criteria. There were no significant differences in age, sex, BMI, duration of anesthesia, and amount of hemorrhage between the 2 groups. We believe that UFTA for OPCAB patients may be possible under carefull decision by extubation criteria. PMID- 27188101 TI - [Thrombotic and Bleeding Risks of Patients on Antiplatelet Therapy Undergoing Major Abdominal Malignancy Surgery]. AB - BACKGROUND: Controversies still exist whether to continue or withdraw aspirin (ASA) perioperatively. This study was performed to determine whether patients on preoperative antiplatelet therapy (APT) benefit from continuing ASA in terms of thrombotic and bleeding risk prevention. METHODS: Among 307 consecutive patients who were on APT preoperatively for the secondary prevention of cardiovascular disease and who underwent elective major abdominal malignancy surgery, 148 patients had all the preoperative APT withdrawn and the remaining 159 patients continued only ASA. Comparisons were made between the 2 groups regarding the rate and the amount of exogenous blood transfusion as well as the incidence of thromboembolic events (TEEs) within 1 month after surgery. RESULTS: The incidence of perioperative TEEs of the APT withdrawn group was significantly higher than that of the ASA group (6.2% vs 0%, P = 0.005), while the rate and the amount of exogenous blood transfusion were not different each other (23.6% vs 17.0%, P = 0.146 and 4 units vs 4 units, P = 0.544, respectively). CONCLUSIONS: Considering the relatively low bleeding risk when continued and the increased thrombotic risk after withdrawal, ASA should be continued perioperatively in patients undergoing major abdominal malignancy surgery. PMID- 27188102 TI - [The Analgesic Sparing Effect of Ketamine for Postoperative Pain Management after Pediatric Surgery on the Body Surface]. AB - BACKGROUND: It is reported that ketamine, a N-methyl-D-aspertate (NMDA) receptor antagonist, can provide analgesic effect improving postoperative pain management and decrease the supplementary analgesic requirement. We investigated the analgesic sparing effect of ketamine for postoperative pain in children undergoing surgery of body surface. METHODS: Fifty eight patients (0-9 yrs) who had surgery of body surface were divided into two groups (ketamine : n = 27, Group K or control : n = 31, Group N). Postoperative analgesia extracted from charts was retrospectively evaluated by the times patients used analgesics until discharge after the operations. Chi-square and Mann-Whitney U tests were used for statistical analysis. Results : The ketamine group received an intrave- nous bolus of ketamine (1 mg - kg-1) before surgical skin incision. However, there were no significant differ- ences of usage (Group K vs Group N : 4/27 vs 7/31, P=0.45) and frequency of supplementary analgesic us- ages (P=0.85) among groups. In addition, there were also no significant demographic differences between the two groups. Conclusions : Our investigation suggests that the intravenous bolus of ketamine (1 mg - kg-1) before surgical skin incision does not decrease the supple- mentary analgesic requirements on postoperative pain management in pediatric surgery of the body surface. PMID- 27188103 TI - [Anesthetic Management with Propofol Alone in a Patient with Hereditary Sensory and Autonomic Neuropathy]. AB - Hereditary sensory and autonomic neuropathy (HSAN) is a rare peripheral nerve disorder associated with sensory dysfunction (pain, touch, and pressure) and various degrees of autonomic dysfunction. We administered general anesthesia for a 54-year-old woman with HSAN type II undergoing amputation of the left hallux. She had reduced sensation for pain, pressure, and temperature since birth and frequently injured her hands and legs. Before the operation, she did not report pain in the hallux. Only propofol was given for anesthesia without use of analgesia. Intraoperatively, her vital signs were stable. To evaluate the sympathetic nervous response to surgical stimulation, we measured the plasma catecholamine levels before tracheal intubation and just before and during surgery. Plasma catecholamine levels were normal at all time points, indicating no sympathetic responses to surgical stimulation. This case suggests that anesthesia for HSAN II patients can be safely managed with propofol alone. PMID- 27188104 TI - [Anesthetic Management of an Infant who Underwent Awake-intubation for Her Pharyngeal Injury Caused by a Toothbrush]. AB - A 2-year-and-4-month-old female infant, 12 kg in weight and 90 cm in height fell off from a table, which was about 1 m height with a toothbrush in her mouth without her parents noticing. Urgent CT scan showed that it penetrated the left side of her oropharyngeal wall to the bifurcation of her right carotid artery. According to the initial assessment, carotid artery seemed intact and there seemed to be no sign of CNS involvement. She underwent general anesthesia for further investigation and operation. We could detect vocal code with ease by inserting Glidescope between her tongue and the toothbrush. After the intubation, we administered fentanyl 25 MUg rocuronium 15 mg and sevoflulane 3-5% to her, and then she underwent arteriography. The neurosurgeon found no sign of major arterial injury nor traumatic aneurysm nor CNS involvement. She went to the ICU intubated after the removal of the toothbrush. She was extubated 5 days after operation. One of the benefits of the Glidescope is that we can share the visual image, and we chose it this time. When we expect a difficult airway during management for oropharyngeal trauma, we have to consider the way to manage the airway. PMID- 27188105 TI - [A Case of General Anesthesia for a Cardiac Transplanted Patient Undergoing Inguinal Hernia Repair under Laparoscopic Surgery]. AB - A 52-year-old man was scheduled for the repair of inguinal hernia recurrence. When he was 48 years of age, he received a heart transplantation due to severe heart failure resulting from ischemic heart disease. When he was 50 years old, he suffered from inguinal hernia, and it was repaired under spinal anesthesia. During this surgery, he experienced pain because of the inadequate effect of anesthesia, but his blood pressure and heart rate were stable. We suspected that this was because of denervation of the heart. On hernia repair for inguinal hernia recurrence, general anesthesia was chosen, induced with midazolam, rocuronium, and fentanyl and maintained with sevoflurane, rocuronium, fentanyl, and remifentanil. The blood pressure was mostly stable during anesthesia, but we noted an increase in the heart rate when the trachea was intubated and extubated and when surgical incision started. This phenomenon may indicate reinnervation of the transplanted heart. We could safely manage anesthesia without invasive monitoring because the transplanted heart functioned favorably and surgery was minimally invasive. PMID- 27188106 TI - [Morphine-induced Anaphylaxis before Induction of Anesthesia]. AB - We describe a case of anaphylaxia that occurred in a 67-year-old man. He was planned to have an operation on mitral valve prolapse (MVP) for mitral regurgitation (MR). Morphine 5 mg was injected intramusculaly 45 min before operation. Since then, he felt itchy sensation around his inguinal region. After he came to the operating room, he felt itchy sensation all over the body. Initially, his vatal signs were stable. We started to give extracellular fluid including ulinastatin 300,000 U, methylprednisolone 2 g, and ranitidine 50 mg. A few minutes later, he had nettle rash all over the body and his blood pressure decreased to 40/20 mmHg, and the heart rate increased to 120 beats x min(-1). Soon after, he had pulseless electric activity (PEA). We started chest compression and tracheal intubation. We injected adrenaline 1 mg. After doing the continuous chest compression for 2 min, he revived. He had continuous medications including dopamine 5 MUg x kg(-1) x min(-1), dobutamine 5 MUg x kg(-1) x min(-1), noradrenaline 0.05 MUg x kg(-1) x min(-1). We cancelled the operation, and he was transfered to the high care unit (HCU), where his blood pressure was 120/65 mmHg, and heart rate 120 beats x min(-1). After 24 hours, we extubated his trachea. In this case, morphine was considered to be the most likely cause for anaphylaxis. PMID- 27188107 TI - [Successful Use of the i-gel and Dexmedetomidine for Tracheal Resection and Construction Surgery in a Patient with Severe Tracheal Stenosis]. AB - A 51-year-old man, 170 cm, 86 kg, was diagnosed with a tracheal tumor existing just below the glottis occupying more than 80% of his tracheal lumen, and was scheduled for tracheal resection and construction. The patient had a strider due to the severe tracheal stenosis. We could insert i-gel easily under dexmedetomidine sedation. After successful i-gel insertion, tracheotomy and endotracheal intubation were performed. Until ETT insertion, the patient maintained spontaneous respiration without any hypoxic event. Followed by ETT insertion, tracheal resection and construction were performed under general anesthesia. After the operation, the patient was extubated and transferred to the intensive care unit (ICU), where he was given DEX infusion to keep the tracheal anastomosis immobilized. There was no serious complication during the perioparative period. PMID- 27188108 TI - [Anesthetic Management of a Patient with May-Hegglin Anomaly]. AB - We report the case of a 52-year-old woman with May-Hegglin Anomaly (MHA) and a platelet count of 1.9 x 10(4) x mm(-3). She was scheduled to undergo abdominal total hysterectomy and adnexectomy with uterine fibroids. Anesthesia was maintained by inhalation of sevoflurane (1.5%), continuous intravenous infusion of remifentanil (0.2-0.3 MUg x kg(-1) x min(-1)), intermittent intravenous infusion of fentanyl (35 MUg), and the transversus abdominis plane block with 20 ml of 0.375% ropivacaine. The amount of bleeding during surgery was 150 ml and her postoperative course was uneventful. MHA is a rare hematological disorder inherited as an autosomal dominant trait that is characterized by thrombocytopenia, giant platelets, and inclusion bodies in the granulocytes. A decrease in platelet count is detectable with a blood test But function of platelets is generally normal. Anesthesiologist should understand the characteristics of MHA, and administer anesthetics without giving platelets. PMID- 27188109 TI - [A Patient with Klippel-Feil Syndrome Having Difficulties in Inserting and Placing an Endotracheal Tube under General Anesthesia]. AB - A patient with Klippel-Feil syndrome had difficulties in inserting and placing an endotracheal tube under general anesthesia. Klippel-Feil syndrome, characterized by cervical vertebral fusion, scoliosis and endocardiosis, is a rare disease. Anesthesiologists should pay attention to management of anesthesia in airway troubles. A 53-year-old woman diagnosed with Klippel-Feil syndrome was scheduled for general anesthesia with intubation. We tried to insert an endotracheal tube using McGRATH MAC, but it was difficult to insert and place the tube. Finally, we managed to insert a 5.5 mm endotracheal tube. The three-dimensional computed tomography (3D-CT) images after the operation, showed tracheal stenosis at the level of the fourth and fifth cervical vertebrae. In cases where airway difficulties are expected, evaluating 3D-CT images might be useful in airway management. PMID- 27188110 TI - [Anaphylactoid Reactions Suspected to Be Caused by Neostigmine in Pediatric Patients under General Anesthesia]. AB - Anaphylactoid reaction is a rapid systemic allergic reaction to many kinds of allergen. The peak age of onset is in the forties and there are not many reports on anaphylactoid reactions in pediatric patients. We report two cases of pediatric patients who underwent surgical treatment on retinoblastoma and developed anaphylactoid reaction probably caused by neostigmine. General anesthesia was induced with fentanyl, sevoflurane, dinitrogen monoxide, and rocronium. The procedure was uneventfully completed. Just after the administration of neostigmine to reverse rocronium, the patients showed red flare on the face and chest, and wheezes were heard, but the vital signs were relatively stable. The rapid onset from the administration of neostigmine to the allergic reaction accompanied by skin and respiratory manifestations strongly suggested the anaphylactoid reaction to neostigmine. PMID- 27188111 TI - [Difficult Ventilation Requiring Emergency Endotracheal Intubation during Awake Craniotomy Managed by Laryngeal Mask Airway]. AB - We report a case of difficult ventilation requiring emergency endotracheal intubation during awake craniotomy managed by laryngeal mask airway (LMA). A 45 year-old woman was scheduled to receive awake craniotomy for brain tumor in the frontal lobe. After anesthetic induction, airway was secured using ProSeal LMA and patient was mechanically ventilated in pressure-control mode. Patient's head was fixed with head-pins at anteflex position, and the operation started. About one hour after the start of the operation, tidal volume suddenly decreased. We immediately started manual ventilation, but the airway resistance was extremely high and we could not adequately ventilate the patient. We administered muscle relaxant for suspected laryngospasm, but ventilatory status did not improve; so we decided to conduct emergency endotracheal intubation. We tried to intubate using Airwayscope or LMA-Fastrach, but they were not effective in our case. Finally trachea was intubated using transnasal fiberoptic bronchoscopy. We discuss airway management during awake craniotomy, focusing on emergency endotracheal intubation during surgery. PMID- 27188112 TI - [Anesthetic Management of a Pediatric Case of Blue Rubber Bleb Nevi Syndrome Combined with Small-intestinal Intussusception]. AB - We report the anesthetic management of a pediatric case of blue rubber bleb nevi syndrome combined with small-intestinal intussusception. A 2-year-old girl was transferred to our hospital for small-intestinal intussusception. Emergent ablation of the upper gastrointestinal tract nevus under general anesthesia was planned. Given the presence of several nevi in the oral and pharyngeal space, we utilized the McGRATH MAC (McGRATH; Aircraft Medical Ltd, United Kingdom) laryngoscope for gentle and stress-free tracheal intubation. The venous line was kept patent preoperatively, and rapid-sequence intubation was performed with the McGRATH (size 2 pediatric blade). A 4.5-mm tracheal tube was inserted uneventfully under direct visualization. The trachea was observed and the tube maintained in a proper position with a bronchofiberscope. During the procedure, cuff volume was regulated to avoid excessive increase by upper gastrointestinal endoscope insertion. The girl was extubated in the operating room and showed no postoperative complications such as hemorrhage or hoarseness. PMID- 27188113 TI - [Anesthetic Management of a Pregnant Woman Undergoing Cesarean Section and Intestinal Tract Perforation Restoration]. AB - We describe anesthetic management of a pregnant woman (weight 42 kg, height 147 cm) with ileus, requiring emergency cesarean section and ileus operation. Cesarean section was performed under spinal anesthesia and epidural anesthesia, and ileus operation was performed under total intravenous general anesthesia. During ileus operation, the blood pressure decreased to 60/30 mmHg and the heart rate increased to 140 beats x min, indicating the intestinal traction syndrome. Repeated injections of phenylephrine 0.1 mg and albumin preparation 5% 1,500 ml were required to restore blood pressure. After the operation, the patient's trachea was extubated. The last level of the spinal anesthesia was T6. PMID- 27188114 TI - [Anesthetic Management of Video-assisted Left Upper Lobectomy in a Patient with Ischemic Heart Disease Using an Intraaortic Balloon Pump]. AB - We report the successful anesthetic management of video-assisted left upper lobectomy in a patient with ischemic heart disease using an intra-aortic balloon pump (IABP). An 81-year-old man with severe ischemic heart disease was scheduled for partial lobectomy for suspected lung cancer under general anesthesia. Although he had severe ischemic heart disease, coronary intervention such as percutaneous cardiac intervention or coronary artery bypass grafting was impossible due to severe coronary stenosis. IABP was instituted through the femoral artery before inducing anesthesia. Tracheal intubation was performed with the McGRATH MAC videolaryngoscope to minimize stress. Surgery was performed uneventfully and the patient was transferred to the intensive care unit under sedation. IABP was removed three hours postoperatively. After confirming no ischemic or vital sign changes, he was extubated the next day. No complications resulting from the IABP were observed. PMID- 27188115 TI - [Anesthetic Management of an Adrenoleukodystrophy Patient for Intrathecal Baclofen Therapy]. AB - A 34-year-old man with adrenoleukodystrophy (ALD) was scheduled for pump system insertion of intrathecal baclofen therapy under general anesthesia. ALD, a rare genetic disorder, is associated with a total body increase in long chain fatty acids caused by defective degradation, and includes various nervous system abnormalities, muscular weakness, in addition to adrenal insufficiency. He had contracture of the both legs, and muscular weakness of the left hand, and Mallampati class III, but no respiratory disability. In the operating room, we administered hydrocortisone 100 mg for steroid coverage, and low-dose midazolam, and fentanyl. As spontaneous breathing remained, we could easily see epiglottis and arytenoid cartilage by McGRATH. Therefore we selected rapid-induction of anesthesia with thiamylal, and rocuronium 40 mg, under cricoid pressure. We avoided propofol. Anesthsia was maintained with sevoflurane and remifentanil, monitoring BIS and train of four. No more rocuronium was administered, and anesthesia was uneventful. Intrathecal baclofen therapy is given to patients who have severe contracture. When we selected general anesthesia, we should be aware of the possibility of muscular weakness, and cannot intubate cannot ventilate scenario. PMID- 27188116 TI - [Effective Dexmedetomidine Administration for the Prevention of Emergence Agitation and Postoperative Delirium in Patients with a History of Postoperative Delirium]. AB - We successfully performed intraoperative dexmedetomidine (DEX) administration for the prevention of emergence agitation or postoperative delirium after lung resection in four patients (71.3 +/- 5.7 year old, 3 males and 1 female) with a past history of postoperative delirium. DEX was started at 0.35-0.45 MUg x kg(-1) x hr(-1) continuously without loading. The average time from DEX initiation to extubation was 141.3 +/- 94.4 minutes. No patient had emergence agitation, and DEX administration was continued until the following morning with monitoring in all patients without any symptoms of delirium. Intraoperative DEX administration may be beneficial for the prevention of emergence agitation or postoperative delirium in patients with a past history of postoperative delirium. PMID- 27188117 TI - [Perioperative Blood Pressure Changes in a Patient Undergoing One-stage Bilateral Nephrectomy for Treatment-resistant Hypertension]. AB - We describe our experience with a 15-year-old girl receiving anesthesia during one-stage bilateral nephrectomy for treatment-resistant hypertension due to chronic renal failure. Approximately 10 minutes after removal of both kidneys, a reduction in blood pressure associated with decreased cardiac contractile force was observed and this necessitated catecholamine administration. However, blood pressure was sufficiently improved approximately 60 minutes later, and catecholamine administration was not necessary after she awoke from anesthesia. Although administration of an antihypertensive agent as required after surgery, as had been the case before surgery, the dose was gradually tapered and we were able to stop drug administration on postoperative day 31. PMID- 27188118 TI - [Airway Management in a Patient with Forestier's Disease]. AB - Airway management in a patient with Forestier's disease can be challenging clinically because this disease may cause not only dysphagia but also airway obstruction due to the compression of the pharynx and esophagus caused by the ossification of anterior longitudinal ligament. We report our anesthetic management in a patient with Forestier's disease. Meanwhile, we studied the causes of difficult airway and the most suitable airway device for a patient with this disease from a standpoint of anatomy of upper airway. Our study indicated the possibility that the most suitable airway device differed depending on the actual location of the ossification of anterior longitudinal ligament in the cervical spine and that more prudent airway management would be required if its lesion location extended to upper cervical spine. PMID- 27188119 TI - [Serious Coagulation Dysfunction in a Patient with Gallstone-related Cholecystitis Successfully Treated with Vitamin K]. AB - An 85-year-old woman with a diagnosis of choledocholithiasis due to common duct stones gradually developed severe coagulation dysfunction over the course of 27 days after hospitalization. Initial clinical findings were fever, general malaise, and obstructive jaundice. She was treated with fasting, and received cephem antibiotics containing N-methyl-thio-tetrazole. Because the common duct stones were not removed endoscopically, cholecystectomy was scheduled. Coagulation on admission was normal, but gradually became impaired. On the scheduled day of the operation, 27 days after hospitalization, coagulation [both prothrombin time (PT) and activated partial thromboplastin time (APTT)] were severely impaired PT, < 10%; PT-international normalized ratio, 6.29; and APTT, 71.6 s. No other abnormalities were identified. Surgery was postponed and antibiotics were discontinued. Simultaneously, administration of vitamin K was initiated. Six days after starting vitamin K, coagulation dysfunction had resolved and the surgery was safely performed under general anesthesia combined with thoracic epidural anesthesia. Care is warranted regarding coagulation dysfunction due to vitamin K deficiency in patients with hepatobiliary disease treated by fasting and antibiotics. PMID- 27188120 TI - [Progression of Cryptogenic Iron Deficiency Anemia and Efficacy of Low-dose Prednisolone in a Rheumatic Case]. AB - Iron deficiency anemia (IDA) in rheumatic patients result from gastrointestinal bleeding owing usually tonon-steroidal anti-inflammatory agent. We experienced a rheumatic female patient in whom cryptogenic IDA deteriorated to 6.9 g x dl(-1) of hemoglobin (Hb) and 4 MUg x dl(-1) of serum iron after surgery of femoral neck fracture. Considering the ascent of inflammatory reaction, we administered 5 mg per day of prednisolone(PSL) to her. In two month, IDA improved to 10.3 g x dl( 1)of Hb and 45 MUg x dl(-1)of serum iron. In conclusion, cryptogenic IDA can deteriorate under 7.0 g x dl(-1)of Hb in rheumatic patients, and the administration of low-dose prednisolone may be effective because of the improved absorbtion of iron and appetite. Anemic condition in rheumatic case needs to be given attention to because of the possibility of its progression without noticing. PMID- 27188121 TI - [Anesthetic Management with Dexmedetomidine in Patients with Serious Mental and Physical Disabilities Undergoing Dental Treatment]. AB - Midazolam and propofol are widely used for the sedation of patients with serious mental and physical disabilities. However, we often experience difficulty in the management of airway and respiratory depression when using these sedatives. Dexmedetomidine (DEX) is being increasingly used as a sedative because of the lack of associated respiratory depression. Here we report anesthetic management with DEX in two patients with disability undergoing dental treatment To avoid movement during treatment, DEX was infused at the rate recommended in the package insert, with an initial administration at 6 MUg x kg(-1) x hr(-1) for 10 min followed by maintenance infusion at 0.7 MUg x kg(-1) x hr(-1). Although the infusion rate seemed to be sufficient for the patients, DEX was not effective and administration of additional sedatives was required. Further, respiratory depression, such as airway obstruction and increase in the concentration of end tidal carbon dioxide, was observed even when DEX was used as the sole agent for inducing sedation. No remarkable change in hemodynamics was observed. Therefore, it is difficult to maintain the sedative state using DEX alone in patients with serious mental and physical disabilities in comparison with patients with no disability. PMID- 27188122 TI - [A Case of Cramps Caused by Lumbar Spinal Stenosis Treated Successfully with Arterial Stenting following Lumbar Sympathetic Ganglion Block]. AB - An 82-year-old woman who had received two operations for lumbar spinal stenosis was treated successfully for persistent nocturnal leg cramps with lumbar sympathetic ganglion block. The stent in the right popliteal artery improved cramps again following the recurrence one month after the block. The head up position in bed against gastroesophageal reflux was found injurious at the time of second recurrence one year after stenting. After the correction of lying position, her legs were in good condition for over one year. Cramps in this case might be caused by disturbances of blood flow supply for motor nerves of the legs by obstructive arterial sclerosis of the nerve injured from root compression. PMID- 27188123 TI - [The Use of a Tracheal Tube for Guiding Nasogastric Tube Insertion]. AB - An obese patient was scheduled for shoulder joint surgery under general anesthesia. After induction of anesthesia and tracheal intubation, insertion of a gastric tube was difficult. A new tracheal tube was prepared, the connecter was removed, and the tube was cut longitudinally. The tube was inserted orally into the esophagus. A gastric tube was passed through the nose, and its tip was taken out of the mouth. The tip of the gastric tube was passed through the tracheal tube, and its correct position in the stomach was confirmed by auscultation of the epigastrium. The tracheal tube was carefully taken out from the esophagus leaving the gastric tube in the stomach. The cut tracheal tube was peeled off from the gastric tube. Correct positioning of the gastric tube was re-confirmed. PMID- 27188124 TI - [The Formative Years of Modern Anesthesiology in Japan--A Dialogue between Hideo Yamamura and Akitomo Matsuki]. PMID- 27188125 TI - Back to the present. PMID- 27188126 TI - A Guided, Conservative Approach for the Management of Localized Mandibular Anterior Tooth Wear. AB - The successful management of the worn mandibular anterior dentition may present an awkward challenge to the dental operator. The purpose of this article is to describe a case report illustrating the use of a guided, three-dimensional protocol for the ultra-conservative and predictable restoration of the worn lower anterior dentition using direct resin composite. This technique utilizes information based on established biomechanical and occlusal principles to fabricate a diagnostic wax-up, which is duplicated in dental stone. This is used to prepare a vacuum-formed modified stent, assisting the clinician to place directly bonded resin composite restorations to restore the worn lower anterior dentition. The technique, described in 2012 and referred to as 'injection moulding' has the potential to offer optimal form, function and an aesthetic outcome in an efficient manner. CPD/Clinical Relevance: This article aims to describe an alternative technique to simplify the processes involved with restoration of worn lower anterior teeth. PMID- 27188127 TI - Modern Endodontic Principles. Part 5: Obturation. AB - Once cleaning and shaping is complete the clinician must obturate the canal. There are many different materials and techniques available each with their own discrete advantages and disadvantages. Whichever technique is used, the goal is to seal the entire prepared length of the root canal. This paper describes how best this may be achieved. CPD/Clinical Relevance: It is incumbent on the clinician to ensure that once the canal has been prepared it is sealed from bacterial re-entry. PMID- 27188128 TI - Gingival Inflammation and Aggressive Periodontitis in a Child with a Specific Antibody Deficiency. AB - Exuberant gingival inflammation accompanied by periodontitis is a rare finding in a very young child and may indicate a defect in the host response. Affected children should be referred to appropriate specialists to establish a definitive diagnosis. A 5-year-old girl presented with persistent gingival inflammation and periodontal destruction. Immunological investigations identified specific polysaccharide antibody deficiency which, when treated, resulted in a significant improvement in the gingival condition. This case illustrates the need for integrated management by a wide range of dental and medical specialists. Antibody deficiency is rare but, if not identified and treated effectively, can be associated with chronic ill health and decreased life expectancy. CPD/Clinical Relevance: This article describes a rare case of gingival inflammation accompanied by periodontitis in a very young child secondary to an underlying host antibody deficiency and details the investigation, management and clinical outcomes. PMID- 27188129 TI - Pain. Part 7: Trigeminal Neuralgia. AB - Trigeminal neuralgia (TN) is also known as 'tic douloureux' (in French, 'painful twitch'). It is a rare chronic facial pain syndrome, characterized by severe, brief, stabbing, 'electric shock-like 'recurrent pain attacks felt in one or more divisions of trigeminal nerve innervation areas. So intense is the elicited pain that TN has a significant effect on a sufferer's quality of life, rendering many patients unable to consider a future with the ongoing threat of recurrent pain. The aim of this article is to discuss the diagnosis and management of this disabling facial pain condition. CPD/Clinical Relevance: As general medical practitioners may struggle differentiating TN from toothache, primary care dentists have an important role in excluding odontogenic cause of pain, diagnosing TN and referring patients to a facial pain clinic for further investigations and multidisciplinary team management. PMID- 27188130 TI - Indications for Cuspal Coverage. AB - Cuspal-coverage restorations are important to preserve the integrity of a weakened tooth against the forces of occlusion. This article discusses the clinical indications for both direct and indirect cuspal-coverage restorations and the evidence supporting their use. Factors that modify a tooth's ability to dissipate normal occlusal forces and the effect cuspal-coverage restorations have on force distribution are examined. Clinical criteria, choice of restorative material and methods for tooth preparation are also discussed. CPD/Clinical Relevance: Re-enforcement of weakened teeth with cuspal-coverage restorations provides a minimally invasive alternative to conventional crowns. PMID- 27188131 TI - Training Plates: A Solution for Patients Unable to Tolerate a Removable Prosthesis. AB - Dealing with patients who are unable to tolerate dentures can present a challenge to the general dental practitioner (GDP). Careful assessment of patients and their dentures will identify any causes of the intolerance to dentures. Training plates are a useful technique that can be used to allow patients to become accustomed to removable prosthesis but will inevitably lengthen the treatment process. CPD/Clinical Relevance: Training plates offer a possible solution to general dental practitioners who treat patients who are struggling to tolerate dentures. PMID- 27188132 TI - A Pathological Fracture of the Mandible due to Osteomyelitis following a Full Dental Clearance. AB - Orofacial infections following dental extractions are a common referral to an oral and maxillofacial department as an emergency, especially when combined with swelling and limited mouth opening. The case presented demonstrates a rare complication of chronic suppurative osteomyelitis with bilateral pathological fractures of the mandible, which occurred following a staged dental clearance. CPD/Clinical Relevance: Dental extractions are one of the most common treatments carried out by oral surgeons and general dental practitioners. This case highlights a rare but encountered complication of routine oral surgery and demonstrates when it is necessary to make an immediate referral to the local oral and maxillofacial surgery unit. PMID- 27188133 TI - Mouth Cancer for Clinicians. Part 8: Referral. AB - A MEDLINE search early in 2015 revealed more than 250,000 papers on head and neck cancer; over 100,000 on oral cancer; and over 60,000 on mouth cancer. Not all publications contain robust evidence. We endeavour to encapsulate the most important of the latest information and advances now employed in practice, in a form comprehensible to healthcare workers, patients and their carers. This series offers the primary care dental team in particular, an overview of the aetiopathogenesis, prevention, diagnosis and multidisciplinary care of mouth cancer, the functional and psychosocial implications, and minimization of the impact on the quality of life of patient and family. Clinical Relevance: This article offers the dental team an overview of referral procedures; oral diagnosis is not always simple and a second opinion can be valuable to all concerned in cases of doubt. PMID- 27188134 TI - Antimuscarinics in Older People: Dry Mouth and Beyond. AB - Many common prescription and over-the-counter medications have antimuscarinic effects. Antimuscarinics are a well recognized cause of dry mouth, with potential to cause other physical and cognitive adverse effects. A comprehensive medication review in a patient presenting with dry mouth can lead to overall health improvements. Scoring systems can be helpful in identifying antimuscarinic drugs and their adverse effects. CPD/Clinical Relevance: Antimuscarinic drug use is prevalent and a common cause of dry mouth. Older people are particularly susceptible to antimuscarinic adverse effects. PMID- 27188135 TI - Dear Editor. PMID- 27188136 TI - Dear Editor. PMID- 27188137 TI - Dear Editor. PMID- 27188138 TI - Dear Editor. PMID- 27188139 TI - Mouth Cancer for Clinicians Part 7 (Dent Update 2016; 50-65). PMID- 27188140 TI - Editor's Response. PMID- 27188141 TI - Clinical Challenges Q&A. 18. Oral Ulceration. Diagnosis. Congenital agranulocytosis (Kostmann syndrome). PMID- 27188142 TI - Technique Tips--The Windowed Partial Denture: An Elastomeric Retention Technique in Patients with Lone-Standing Teeth. PMID- 27188143 TI - [The Changes in the Hemodynamic Activity of the Brain during Moroe Imagery Training with the Use of Brain-Computer Interface]. AB - With the use of functional MRI (fMRI), we studied the changes in brain hemodynamic activity of healthy subjects during motor imagery training with the use brain-computer interface (BCI), which is based on the recognition of EEG patterns of imagined movements. ANOVA dispersion analysis showed there are 14 areas of the brain where statistically sgnificant changes were registered. Detailed analysis of the activity in these areas before and after training (Student's and Mann-Whitney tests) reduced the amount of areas with significantly changed activity to five; these are Brodmann areas 44 and 45, insula, middle frontal gyrus, and anterior cingulate gyrus. We suggest that these changes are caused by the formation of memory traces of those brain activity patterns which are most accurately recognized by BCI classifiers as correspondent with limb movements. We also observed a tendency of increase in the activity of motor imagery after training. The hemodynamic activity in all these 14 areas during real movements was either approximatly the same or significantly higher than during motor imagery; activity during imagined leg movements was higher that that during imagined arm movements, except for the areas of representation of arms. PMID- 27188144 TI - [Arm Motor Function Recovery during Rehabilitation with the Use of Hand Exoskeleton Controlled by Brain-Computer Interface: a Patient with Severe Brain Damage]. AB - We studied the dynamics of motor function recovery in a patient with severe brain damage in the course of neurorehabilitation using hand exoskeleton controlled by brain-computer interface. For estimating the motor function of paretic arm, we used the biomechanical analysis of movements registered during the course of rehabilitation. After 15 weekly sessions of hand exoskeleton control, the following results were obtained: a) the velocity profile of goal-directed movements of paretic hand became bell-shaped, b) the patient began to extend and abduct the hand which was flexed and adducted in the beginning of rehabilitation, and c) the patient began to supinate the forearm which was pronated in the beginning of rehabilitation. The first result is an evidence of the general improvement of the quality of motor control, while the second and third results prove that the spasticity of paretic arm has decreased. PMID- 27188146 TI - [Classification of EEG Patterns of Imagined Rhythmic Movements of the Fingers of One Hand]. AB - The article presents the results of classification of EEG patterns registered during imagined rhytmic movements of the fingers of the right hand (little, thumb, index, middle fingers) in 8 healthy subjects. The subjects imagined finger movements in a given rhythm; no external stimuli were used. A two-level committee of classifiers was developed for decoding: the first level included support vector machines and artificial neural networks; the second level included artificial neural network used for generalizing. As the key parameters for classification, we used the area of zone under the envelope of EEG signal and the length of the envelope calculated in sliding time window for leads F3, C3 and Cz in system 10-20 were chosen as the key features for signals of sensorimotor and adjoining frontal area cortex contralateral to movements. The accuracy of classification of single trials for 4 movements averaged for all subjects for the pair of leads F3-C3 was 50 +/- 7% [SD] (maximal - 58%); for the pair of leads C3 Cz, 46 +/- 11% [SD] (maximal - 62%); theoretical guessing level is 25%. PMID- 27188145 TI - [Brain-Computer Interface: the First Clinical Experience in Russia]. AB - Motor imagery is suggested to stimulate the same plastic mechanisms in the brain as a real movement. The brain-computer interface (BCI) controls motor imagery by converting EEG during this process into the commands for an external device. This article presents the results of two-stage study of the clinical use of non invasive BCI in the rehabilitation of patients with severe hemiparesis caused by focal brain damage. It was found that the ability to control BCI did not depend on the duration of a disease, brain lesion localization and the degree of neurological deficit. The first step of the study involved 36 patients; it showed that the efficacy of rehabilitation was higher in the group with the use of BCI (the score on the Action Research Arm Test (ARAT) improved from 1 [0; 2] to 5 [0; 16] points, p = 0.012; no significant improvement was observed in control group). The second step of the study involved 19 patients; the complex BCI-exoskeleton (i.e. with the kinesthetic feedback) was used for motor imagery trainings. The improvement of the motor function of hands was proved by ARAT (the score improved from 2 [0; 37] to 4 [1; 45:5] points, p = 0.005) and Fugl-Meyer scale (from 72 [63; 110 ] to 79 [68; 115] points, p = 0.005). PMID- 27188147 TI - [The Activation of Interlimb Interactions Increase the Motor Output in Legs in Healthy Subjects under the Conditions of Arm and Leg Unloading]. AB - We studied the effect of arm movements and movements of separate arm joints on the electrophysiological and kinematic characteristics of voluntary and vibration triggered stepping-like leg movements under the conditions of horizontal support of upper and lower limbs. The horizontal support of arms provided a significantly increase in the rate of activation of locomotor automatism by non-invasive impact on tonic sensory inputs. The addition of active arm movements during involuntary rhytmic stepping-like leg movements led to an increase in EMG activity of hip muscles and was accompanied by an increase in the amplitude of hip and shin movements. Passive arm movements had the same effect on induced leg movements. The movement of the shoulder joints led to an increase in the activity of hip muscles and an increase in the amplitude of movements of the knee and hip joints. At the same time, the movement of forearms. and wrists had similar facilitating effect on electrophysiological and kinematic characteristics of rhytmic stepping like movements, but influenced the distal segments of legs to a greater extent. Under the conditions of sub-threshold vibration of leg muscles, voluntary arm movements led to the activation of involuntary rhytmic stepping movements. During voluntary leg movements, the addition of arm movements had a significantly smaller impact on the parameters of rhytmic stepping than during involuntary leg movements. Thus, the simultaneous movements of upper and lower limbs are an effective method of activation of neural networks connecting the rhythm generators of arms and legs. Under the conditions of arm and leg unloading, the interactions between the cervical and lumbosacral segments of the spinal cord seem to play the major role in the impact of arm movements on the patterns of leg movements. The described methods of activation of interlimb interactions can be used in the rehabilitation of post-stroke patients and patients with spinal cord injuries, Parkinson's disease and other neurological diseases. PMID- 27188148 TI - [Changes in the Functional Connectivity of Motor Zones in the Use of Multimodal Exoskeleton Complex "Regent" in the Neurorehabilitation of Post-Stroke Patients]. AB - The article discusses the effect of a course of treatment with the use of multimodal complex exoskeleton (MCE) "Regent" on the reorganization of cortical locomotor zones in 14 patients with post-stroke hemiparesis, mainly atthe chronic stage of the disease. Before the course of treatment, we identified specific areas of activation in the primary sensorimotor and supplementary motor areas and the inferior parietal lobules in both affected and healthy hemispheres by means of functional MRI (fMRI) with the use of special passive sensorimotor paradigms. After the course of treatment with MCE, we observed an improvement of temporal characteristics of walking; it was accompanied by a decrease in the activation zones of inferior parietal lobules, especially in the healthy hemisphere, and by a significant increase in the activation zone of primary sensorimotor and supplementary motor areas. The analysis of the functional connectivity of studied zones before and after the course of treatment with MCE showed significant changes in intra- and interhemispheric interactions. PMID- 27188149 TI - [Non-Invasive Methods for the Control of Human Spinal Locomotory Systems]. AB - We studied the interrelations between the activation of the receptors of musculoskeletal system and the spinal cord stimulation in the regulation of locomotor behavior in healthy subjects. We observed the effect of afferent stimulation on the patterns of stepping movements caused by percutaneous stimulation of spinal cord. It was found that the combination of percutaneous spinal cord stimulation and vibrostimulation increases the amplitude of leg movements. It was shown that the vibrostimulation of limb muscles at a frequency of less than 30 Hz may be used for comtrolling involuntary movements, caused by non-invasive stimulation of the spinal cord. PMID- 27188150 TI - [The Influence of Emotional Coloring of Images on Visual Working Memory in Adults and Adolescents]. AB - The influence of emotional valence (positive, negative and neutral) of realistic images on the visual working memory (WM) capacity was studied in adults (N = 40) and adolescents (N = 17). In adults, emotional coloring of stimuli increased the reaction time and decreased the accuracy of WM task performance. This effect was more pronounced for negative than for positive valence: the reaction time has its maximum value for negative emotional stimuli and minimum value for neutral ones with significant differences between all three valences; the accuracy was lower for negative stimuli than for both positive and neutral stimuli. Comparing with adults, adolescents aged 14-16 years showed the lower indices of the performance accuracy and rate during the retention of neutral and positive stimuli in WM. In this group, no significant influence of emotional valence of visual stimuli on the accuracy of WM task performance was found. PMID- 27188151 TI - [Oxidation Stress Markers Dynamics in the Experiment of Long-Term Antiorthostatic Hypokinesia (Retrospective Study)]. AB - In blood serum of 9 volunteers aged 27 to 42, participated in the experiment with 370-day antiorthostatic hypokinesia (-5 degrees), the lipid peroxidation derivates concentration--diene conjugates (DC), malonic dialdehyde (MDA), Schiff bases (SB) as well as antioxidant defense system indices--tocopherol (TP) concentration and total antioxidative activity level (AOA) were measured. The volunteers were divided into two groups subjected to physical training regimes and used prophylactic measures. In both groups the lipoperoxidation processes initial stages depression (by 54-73%) was observed starting from 50th day, thus the lipid peroxidation final product--SB level was decreased (by 50-61%) only to the 230 day and remains approximately at the same level till the end of the experiment. The restorative period was characterized by decreasing (in 1.6-2.3 times) of MDA and SB concentrations. The decrease in lotal AOA during the aftereffect period was detected in all volunteers, and its level was significantly lower physiological norm range. Probably, long-term adaptation to the simulated weightlessness conditions is accompanied by expressed decrease in biological oxidation processes intensity and significant stress effect, as indicates by essential depression of lipid free radical oxidation in the course of the experiment. At the same time the restorative period after 370-day antiorthostatic hypokinesia was characterized by significantly expressed and prolonged readaptation stress progress. It is evidenced by practically twofold decrease in lipoperoxidation processes intensity against significant increase in TP concentration and water-soluble antioxidants functional reserves exhaustion. Lipid peroxidation activation absence in all terms of examination reflects appropriate compensation of studying impact by volunteers. PMID- 27188152 TI - [The Details of Thermoesthesia-and-Algesthesia State in Patients with Idiopathic Scoliosis of III-IV Degree]. AB - Sensitivity in patients with adolescent idiopathic scoliosis remains insufficiently studied. The details of thermoesthesia-and-algesthesia state were studied in adolescent patients with III-IV Degree idiopathic scoliosis. Thermoesthesia-and-algesthesia was evaluated in Th1-S1 dermatomes on the right and on the left using an electric esthesiometer. Thermoesthesia-and-algesthesia disorders of different severity degree have been established to be observed in all patients in all the dermatomes studied, manifesting themselves as hypesthesia, hyperesthesia, and thermoesthesia absence. The disorders of thermoesthesia-and-algesthesia were not of local character; but they went beyond the level of the spine deformity. Maximum negative changes in thermoesthesia-and algesthesia were registered in the dermatomes corresponding to the apex of thoracic spine deformity (Th8, Th9, Th10) where the lowest percentage of patients with normal algesthesia thresholds is observed being combined with the decreased number of patients with thermoesthesia thresholds within the norm. PMID- 27188153 TI - SENSORIMOTOR REGULATION OF MOVEMENTS: NOVEL STRATEGIES FOR THE RECOVERY OF MOBILITY. AB - A series of observations have provided important insight into properties of the spinal as well as supraspinal circuitries that control posture and movement. We have demonstrated that spinal rats can regain full weight-bearing standing and stepping over a range of speeds and directions with the aid of electrically enabling motor control (eEmc), pharmacological modulation (fEmc), and training. Also, we have reported that voluntary control movements of individual joints and limbs can be regained after complete paralysis in humans. However, the ability to generate significant levels of voluntary weight-bearing stepping with or without epidural spinal cord stimulation remains limited. Herein we introduce a novel method of painless transcutaneous electrical enabling motor control (pcEmc) and sensory enabling motor control (sEmc) strategy to neuromodulate the physiological state of the spinal cord. We have found that a combination of a novel non invasive transcutaneous spinal cord stimulation and sensory-motor stimulation of leg mechanoreceptors can modulate the spinal locomotor circuitry to that enables voluntary rhuthmic locomotor movements. PMID- 27188154 TI - [Neurophysiological Foundations and Practical Realizations of the Brain-Machine Interfaces the Technology in Neurological Rehabilitation]. AB - Technology brain-computer interface (BCI) based on the registration and interpretation of EEG has recently become one of the most popular developments in neuroscience and psychophysiology. This is due not only to the intended future use of these technologies in many areas of practical human activity, but also to the fact that IMC--is a completely new paradigm in psychophysiology, allowing test hypotheses about the possibilities of the human brain to the development of skills of interaction with the outside world without the mediation of the motor system, i.e. only with the help of voluntary modulation of EEG generators. This paper examines the theoretical and experimental basis, the current state and prospects of development of training, communicational and assisting complexes based on BCI to control them without muscular effort on the basis of mental commands detected in the EEG of patients with severely impaired speech and motor system. PMID- 27188155 TI - [Artificial Feedback for Invasive Brain-Computer Interfaces]. AB - During the last two decades, considerable progress has been made in the studies of brain-computer interfaces (BCIs)--devices in which motor signals from the brain are registered by multi-electrode arrays and transformed into commands for articial actuators such as cursors and robotic devices. This review is focused on one problem. Voluntary motor control is based on neurophysiological processes which depend heavily on the afferent innervation of skin, muscles and joints. Thus, invasive BCI has to be based on a bidirectional system in which motor control signals are registered by multi-channel micro-electrodes implanted in motor areas, while tactile, proprioceptive and other useful signals are transported back to the brain through spatial-temporal patterns of intracortical microstimulation (ICMS) delivered to sensory areas. In general, the studies of invasive BCIs have advanced in several directions. The progress of BCIs with articial sensory feedback will not only help patients, but will also expand knowledge base in the field of human cortical functions. PMID- 27188156 TI - [Evaluation of the efficacy of powered and manual toothbrushes in preventing oral diseases (Systematic review with meta-analysis)]. AB - BACKGROUND: The removal of dental plaque plays an essential role in the maintenance of oral health. Numerous powered and manual toothbrushes were manufactured to achieve this goal, but even up to this day different opinions and research results have been revealed to assess the priority of the mentioned devices. AIM: Comparison of powered and manual toothbrushes on the basis of periodontal parameters and safety. MATERIALS AND METHODS: Electronic search of the databases of MEDLINE and EMBASE (until May 2014) was carried out with the help of keywords in order to find relevant trials. The inclusion criteria were as follows: randomised controlled clinical trials, adult population, the presence of at least 15 permanent teeth. Split-mouth trials and interventions carried out by dental professionals, were excluded. Primary outcomes were the changes of plaque and gingival indices, while secondary outcomes were probing pocket depth (PPD), safety and quality assessment. The effect-size of the interventions was expressed by the standardised mean difference (SMD) with 95% confidence interval (CI). Random-effects models were performed. RESULTS: Electronic search resulted in 173 hits. 21 trials with the total number of 1500 subjects were then eligible for the meta-analysis. Both toothbrushes were safe, without considerable side effects on soft or hard tissues. Powered toothbrushes seemed to be generally more effective in removing plaque (-9%), reducing gingivitis (-6%) and preventing calculus formation. The SMDs for plaque and gingival indices were -0,40 (95% Cl: -0,95 to 0,16) and -0,29 (95% Cl: -0,56 to -0,03) respectively, in favour of the powered devices. There was no significant difference in changes of PPD. By further dividing the powered toothbrushes according to their mode of action, the plaque removal effect of the rotation oscillation (plus three dimensional), side to side sonic and ultrasonic toothbrushes seemed to be significantly better, than their manual ones, while the counter oscillation and the ionic toothbrushes did not perform better. Quality assessment and sensitivity analysis revealed various types of bias up to a certain extent. Consequently, no trial was found to be eligible for the highest quality criteria. CONCLUSIONS: The investigated rotation oscillation and vibrating toothbrushes appeared to be statistically more effective than their manual counterparts, although there is little known about its clinical relevance. The advantage of the electric toothbrushes disappears in case of adequately instructed and motivated patients that highlights the importance of individualised oral hygiene education. The design of the trials shows high heterogeneity, therefore their clinical implications should be handled carefully. PMID- 27188157 TI - [In 2015, the Orsos Memorial Medal was awarded to Dr. Zoltan Vass]. PMID- 27188158 TI - [Incidence of combination syndrome based on the orthopantomograms made between 2009 es 2014 at the Department of Prosthodontics, University of Pecs, Hungary]. AB - The treatment of patients having a completely edentulous maxillary arch and lower anterior teeth present is frequent in the dental practice. In these cases some specific changes can be detected in the oral cavity and on orthopantomograms. These signs were summarized and described first by Kelly (1972). Aim of the study was to examine the presence of the specific signs of the combination syndrome among the patients between 2009 and 2014. With the help of the electronic patient registry system used by the University of Pecs, 319 patients were filtered who were diagnosed with anodontia code (K0000 International Classification of Diseases (ICD)) in the examined period. 220 patients' orthopantomograms were evaluated searching for specific symptoms of the combination syndrome. 34 patients had complete edentulous maxilla and anterior teeth in the mandible. 4 patients (11.7%) showed the main sign of the combination syndrome, i.e. the maxillary anterior bone loss. Hypertrophy of maxillary tuberosity (9 cases, 26.4%), extrusion of the lower anterior teeth (6 cases, 17.6%) and great resorption of the distal mandibular ridge (16 cases, 47%) was diagnosed on the X rays. The clinical examination of three patients supported the radiological findings. The combination syndrome was detectable, but the incidence rate was lower in this population in comparison with the data available in dental scientific publications. PMID- 27188159 TI - [Comparison of sorting of fluorescently and magnetically labelled dental pulp stem cells]. AB - Stem cells are present in many tissues, such as dental pulp. Stem cells can be easily isolated from dental pulp because third molars are often removed from patients. Stem cells could be separated from the tissue derived heterogeneous cell population. There are two main methods to separate a cell type from the other ones: the fluorescence activated cell sorting (FACS) and the magnetic activated cell sorting (MACS). The aim of this study was to compare these methods' effect on cell surviving and population growth after sorting on dental pulp cells. The anti-STRO-1 antibody was used as primary antibody to specifically label stem cells. Two secondary antibodies were used: magnetic or fluorescent labelled. We sorted the cells by MACS or by FACS or by combination of both (MACS FACS). Our results show that the effectivity of MACS and FACS sorting are comparable while of MACS-FACS was significantly higher (MACS 79.53 +/- 5.78%, FACS 88.27 +/- 3.70%, MACS-FACS 98.43 +/- 0.67%). The cell surviving and the post sorting population growth, on the contrary, are very different. The cell population is growing on first week after MACS but after FACS did not. Moreover, after MACS-FACS, on first week the cell number of population decreased. Taken together, our results suggest to use MACS instead of FACS, at least in case of sorting dental pulp stem cells with anti-STRO-1 antibody. PMID- 27188160 TI - [Report from the 20th Congress of the European Association of Dental Public Health, held in 2015]. PMID- 27188161 TI - Chinese oncologists' knowledge, attitudes and practice towards palliative care and end of life issues. AB - BACKGROUND: Oncologists' knowledge and attitudes to palliative care (PC) and end of life (EOF) should be highlighted in order to give them effective education. This study is intended to provide a descriptive analysis of oncologists' knowledge, attitudes and practice toward PC and EOF issues in Mainland China. METHODS: The questionnaire survey with 24 items investigating oncologists' demographic information, knowledge and attitudes toward PC and EOF issues was conducted among Chinese Oncology clinicians. RESULTS: The participants had a mean of 10.10 years practice in oncology. 43 (31.2%) participants had received PC education. 73.9% of the participants believed that PC should be considered when patients were not suitable to take surgery, radiotherapy, chemotherapy and other anti-cancer therapies. 72.5% of the participants believed that early PC integration can improve the quality of life in patients. Most of the oncology clinicians (73.9%) believed that the doctor-in-charge was the appropriate person to inform patients of the diagnosis. However, only 11 participants chose to inform the diagnosis and disease prognosis to the patients, whereas 39.9% of the participants chose to disclose it to Family/Caregivers first. Besides, Chinese oncologists were obviously unfamiliar with the concepts of euthanasia and related issues. CONCLUSIONS: This study indicated the insufficient knowledge toward PC and related issues of the Chinese oncologists. More attention should be paid on the education of PC among Oncologists in Mainland China. PMID- 27188162 TI - False non-susceptible results of tigecycline susceptibility testing against Enterobacteriaceae by an automated system: a multicentre study. PMID- 27188163 TI - Erratum to: A redesigned CRISPR/Cas9 system for marker-free genome editing in Plasmodium falciparum. PMID- 27188164 TI - Stillbirth and neonatal death rates across time: the influence of pregnancy terminations and birth defects in a Western Australian population-based cohort study. AB - BACKGROUND: The stillbirth rate in most high income countries reduced in the early part of the 20(th) century but has apparently been static over the past 21/2 decades. However, there has not been any account taken of pregnancy terminations and birth defects on these trends. The current study sought to quantify these relationships using linked Western Australian administrative data for the years 1986-2010. METHODS: We analysed a retrospective, population-based cohort of Western Australia births from 1986 to 2010, with de-identified linked data from core population health datasets. RESULTS: The study revealed a significant decrease in the neonatal death rate from 1986 to 2010 (6.1 to 2.1 neonatal deaths per 1000 births; p < .01), while the overall stillbirth rate remained static. The stillbirth trend was driven by deaths in the extremely preterm period (20-27 weeks; which account for about half of all recorded stillbirths and neonatal deaths), masking significant decreases in the rate of stillbirth at very preterm (28-31 weeks), moderate to late preterm (32-36 weeks), and term (37+ weeks). For singletons, birth defects made up an increasing proportion of stillbirths and decreasing proportion of neonatal deaths over the study period-a shift that appears to have been largely driven by the increase in late pregnancy terminations (20 weeks or more gestation). After accounting for pregnancy terminations, we observed a significant downward trend in stillbirth and neonatal death rates at every gestational age. CONCLUSIONS: Changes in clinical practice related to pregnancy terminations have played a substantial role in shaping stillbirth and neonatal death rates in Western Australia over the 21/2 decades to 2010. The study underscores the need to disaggregate perinatal mortality data in order to support a fuller consideration of the influence of pregnancy terminations and birth defects when assessing change over time in the rates of stillbirth and neonatal death. PMID- 27188165 TI - Molecular profile of dissociative drug ketamine in relation to its rapid antidepressant action. AB - BACKGROUND: The NMDA receptor antagonist ketamine was found to act as a fast acting antidepressant. The effects of single treatment were reported to persist for days to weeks, even in otherwise treatment-refractory cases. Identification of the mechanisms underlying ketamine's antidepressant action may permit development of novel drugs, with similar clinical properties but lacking psychotomimetic, sedative and other side effects. METHODS: We applied whole genome microarray profiling to analyze detailed time-course (1, 2, 4 and 8 h) of transcriptome alterations in the striatum and hippocampus following acute administration of ketamine, memantine and phencyclidine in C57BL/6 J mice. The transcriptional effects of ketamine were further analyzed using next-generation sequencing and quantitative PCR. Gene expression alterations induced by the NMDA antagonists were compared to the molecular profiles of psychotropic drugs: antidepressants, antipsychotics, anxiolytics, psychostimulants and opioids. RESULTS: We identified 52 transcripts (e.g. Dusp1, Per1 and Fkbp5) with altered expression (FDR < 1 %) in response to treatment with NMDA receptor antagonists. Functional links that connect expression of the regulated genes to the MAPK, IL-6 and insulin signaling pathways were indicated. Moreover, ketamine-regulated expression of specific gene isoforms was detected (e.g. Tsc22d3, Sgk1 and Hif3a). The comparison with other psychotropic drugs revealed that the molecular effects of ketamine are most similar to memantine and phencyclidine. Clustering based on expression profiles placed the NMDA antagonists among fluoxetine, tianeptine, as well as opioids and ethanol. CONCLUSIONS: The identified patterns of gene expression alteration in the brain provided novel molecular classification of ketamine. The transcriptional profile of ketamine reflects its multi-target pharmacological nature. The results reveal similarities between the effects of ketamine and monoaminergic antidepressants that may explain the mechanisms of its rapid antidepressant action. PMID- 27188166 TI - Clinimetric properties of the ASAS health index in a cohort of Italian patients with axial spondyloarthritis. AB - BACKGROUND: The impact of axial spondyloarthritis (axSpA) is considerable in many aspects of the life. Over the last decades, many efforts have been conducted to develop useful tools for the evaluation of disease activity. However, since the development of Assessment of SpondyloArthritis international Society Health Index (ASAS HI), no specific freely questionnaire to describe the overall picture of impairments, limitations and restrictions in activities or social partecipation were available. The aims of this study were to test the feasibility, reliability, and construct validity of the ASAS HI, in order to compare its clinimetric properties with the current available measures of disease activity, functional limitation and health status assessments in patients with axSpA. METHODS: A cohort of 140 consecutive axSpA has been the object of study. The feasibility has been determined by the percentage of patients who were able to complete the questionnaire by themselves and by the time employed to fill the ASAS HI. The reliability has been evaluated performing a test-retest of the questionnaire within a week. The construct validity was examined in three ways. First, we examined construct convergent validity by correlating the scores of the ASAS HI with the Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP/ESR, the Simplified Ankylosing Spondylitis Disease Activity Score (SASDAS), the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Metrology Index (BASMI), the Bath Ankylosing Spondylitis Functional Index (BASFI), the Ankylosing Spondylitis Quality of Life scale (ASQoL) and the EuroQoL Five Dimensional Questionnaire (EQ-5D). Secondly, we have created patient groups based on the patients' activity ranks (ASDAS-CRP and SASDAS categorisation) within the cohort to assess discriminative accuracy. Additionally, to distinguish patients with active and non-active disease and to assess their respective cut-off points values, the receiver operating characteristic (ROC) curve analysis was used. Thirdly, we analyzed the contribution of demographic (age, sex, and disease duration) and clinical variables (number of comorbidity and disease activity by ASAS-CRP) to the attainment of an ASAS HI condition by stepwise logistic regression. RESULTS: The mean time to complete the ASAS HI was 1.92 +/- 0.76 min. Overall, the ASAS HI questionnaire was correctly completed by the majority of the patients (99,2 %). Coefficients of agreement between ASAS HI scores on first and second administrations were excellent and all items showed very good agreement (ICC = 0.976; range 0.966 to 0.982). The ASAS HI was correlated significantly with all other comparator scores (p <0.0001). The highest correlations were seen with ASQoL (rho 0.784; p <0.0001), BASFI (rho 0.671; p <0.0001) and SASDAS (rho 0.640; p <0.0003). On categorizing patients into different cut-off point of disease activity, with respect to the both ASDAS-CRP and SASDAS, ASAS HI scores were highly significantly different between the four categories (p <0.0001). An ASAS HI value of 4.0 resulted the cut-off with the highest combination of sensitivity and specificity (82.6 % and 86.3 %, respectively) to define the inactive disease. In the logistic regression model, high disease activity measured by ASDAS-CRP (coefficient 2.39; p <0.0001), was the only independent variable associated with ASAS HI. CONCLUSIONS: The results reported in this study confirm the feasibility, reliability and validity of the ASAS HI in Italian patients with axSpA. Even if ASAS HI is not a disease activity index, of particular interest appears the cut off value of 4.0, under which could be defined the inactive disease. This value could represent an easily applicable starting point in daily clinical practice. PMID- 27188167 TI - Bone marrow-derived cells are recruited by the melanoma tumor with endothelial cells contributing to tumor vasculature. AB - PURPOSE: Tumor expansion is dependent on neovascularization, a process that requires sustained new vessel formation. Although the critical role of angiogenesis by endothelial sprouting in this process, controversy still prevails on whether angiogenesis involving bone marrow-derived endothelial cells, does contribute to this process. This study aims to evaluate the recruitment of bone marrow-derived cells by the melanoma tumor, including endothelial cells, and if they contribute to angiogenesis. METHODS: A chimeric mouse model of GFP bone marrow was used to induce melanoma tumors derived from murine B16-F10 cell line. These tumors were evaluated for the presence of myeloid cells (CD11b), T lymphocytes (CD3, CD4 and CD8) and endothelial cells (VEGFR2 and CD31) derived from bone marrow. RESULTS: Mice transplanted with GFP+ cells showed significant bone marrow chimerism (90.9 +/- 0.87 %) when compared to the GFP transgenic mice (90.66 +/- 2.1 %, p = 0.83) demonstrating successful engraftment of donor bone marrow stem/progenitor cells. Analysis of the murine melanoma tumor showed the presence of donor cells in the tumors (3.5 +/- 1.7 %) and interestingly, these cells represent endothelial cells (CD31+ cells; 11.5 +/- 6.85 %) and myeloid cells (CD11b+ cells; 80 +/- 21 %), but also tumor-infiltrating lymphocytes (CD8+ T cells, 13.31 +/- 0.2 %; CD4+ T-cells, 2.1 +/- 1.2 %). Examination of the tumor endothelium by confocal microscopy suggests the presence of donor CD31+/GFP+ cells in the wall of some blood vessels. CONCLUSION: This study demonstrates that bone marrow-derived cells are recruited by the murine melanoma tumor, with myeloid cells and CD4 and CD8 T lymphocytes migrating as antitumor immune response, and endothelial cells participating of the tumor blood vessels formation. PMID- 27188168 TI - P-Hydroxycinnamaldehyde Induces B16-F1 Melanoma Cell Differentiation via the RhoA MAPK Signaling Pathway. AB - BACKGROUND/AIMS: Due to its antitumor and gastroprotective properties, cochinchina momordica seed (CMS), has been widely used to treat cancer patients in Asia. Our previous reports have shown that CMS is able to induce the differentiation of B16-F1 melanoma cells. However, its functional component and mechanism remain unclear and are addressed in this study. METHODS AND RESULTS: CMSP (p-hydroxycinnamaldehyde isolated from CMS) inhibited the proliferation, migration and invasiveness of B16-F1 cells both in vivo and in vitro. CMSP also induced the differentiation of B16-F1 cells, as characterized by dendrite-like outgrowth, increased melanogenesis and enhanced tyrosinase activity. Furthermore, CMSP treatment reduced the level of malignant markers of melanoma, specifically S 100B and melanoma-derived growth regulatory protein precursor (MIA), in a concentration-dependent manner. According to a western blot analysis, B16-F1 cells treated with CMSP exhibited a sustained increase in p-P38 and decreased activities of ERK and JNK. Our data further indicated that the downregulation of GTP-RhoA, which was mediated by increased cAMP release, was involved in CMSP induced changes in MAPK, while LPA (Lysophosphatidic acid) partially reversed CMSP-induced B16 cell differentiation. CONCLUSION: These results demonstrated that CMSP-induced differentiation of B16F1 cells may occur through the RhoA-MAPK axis, which suggests a new potential strategy for melanoma treatment. PMID- 27188169 TI - Erratum to: Inter-regulation of IGFBP1 and FOXO3a unveils novel mechanism in ursolic acid-inhibited growth of hepatocellular carcinoma cells. PMID- 27188170 TI - WCO-IOF-ESCEO World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases. PMID- 27188171 TI - World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO IOF-ESCEO 2016): Plenary Lecture Abstracts. PMID- 27188172 TI - World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO IOF-ESCEO 2016): Oral Communication Abstracts. PMID- 27188174 TI - World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO IOF-ESCEO 2016): Educational Lecture Abstract. PMID- 27188173 TI - World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO IOF-ESCEO 2016): ESCEO Symposia Abstracts. PMID- 27188175 TI - World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO IOF-ESCEO 2016): Meet-the-Expert Sessions. PMID- 27188176 TI - World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO IOF-ESCEO 2016): Poster Abstracts. PMID- 27188177 TI - World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO IOF-ESCEO 2016): Satellite Symposia Abstracts. PMID- 27188178 TI - World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO IOF-ESCEO 2016): Non-sponsored Symposia Abstracts. PMID- 27188179 TI - World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO IOF-ESCEO 2016): Committee of National Societies Abstracts. PMID- 27188181 TI - Treating Diabetes in Patients with Heart Failure: Moving from Risk to Benefit. AB - Over the past two decades, therapeutics for diabetes have evolved from drugs with known heart failure risk to classes with potential benefit for patients with heart failure. As many as 25 to 35 % of patients with heart failure carry a diagnosis of type 2 diabetes mellitus. Therefore, newer drug classes including dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide 1 (GIP-1) agonists, and sodium-glucose cotransporter 2 (SGLT-2) inhibitors are being examined for cardiovascular safety as well as their effects on left ventricular function, quality of life, and other measures of disease progression. The purpose of this review is to summarize the existing evidence on these classes of anti diabetic agents in patients with heart failure. PMID- 27188182 TI - Idiopathic intracranial hypertension occurred after spinal surgery: report of two rare cases and systematic review of the literature. AB - BACKGROUND: Idiopathic intracranial hypertension (IIH) is a relatively rare syndrome of increased intracranial pressure of unknown etiology. It is characterized by cerebrospinal fluid (CSF) opening pressure more than 250 mmH2O, with normal cranial imaging and CSF content. IIH occurred after spinal surgery is extremely rare. METHODS: We present two IIH cases occurred after spinal surgery and conduct a systematic review of articles reporting IIH occurred after spinal surgery. RESULTS: The first patient underwent a posterior decompression and fixation for cervical fractures. IIH symptoms appeared 3 days postoperatively and gradually resolved with appropriate medication. The second patient underwent posterior spinal fusion with segmental instrumentation for congenital scoliosis. IIH symptoms appeared 5 days postoperatively and the patient died due to the irreversible intracranial hypertension although underwent intensive care and treatment. The literature review revealed that there were only five cases of IIH occurred after spinal surgery reported till date. CONCLUSIONS: IIH occurred after spinal surgery is relatively rare; the diagnosis is based upon exclusion of other diseases. IIH should be kept in mind in patients underwent spinal surgery as it could develop into irreversible intracranial hypertension. PMID- 27188183 TI - Globular CTRP9 inhibits oxLDL-induced inflammatory response in RAW 264.7 macrophages via AMPK activation. AB - C1q-TNF-related protein-9 (CTRP9) is increasingly recognized as a promising cardioprotective adipocytokine, which regulates biological processes like vascular relaxation, proliferation, apoptosis, and inflammation. We recently showed that CTRP9 enhanced carotid plaque stability by reducing pro-inflammatory cytokines in macrophages. However, the underlying molecular mechanism of CTRP9 on anti-inflammatory response in macrophages still remains unclear. We demonstrated that globular CTRP9 (gCTRP9) significantly reduced oxidized low-density lipoprotein (oxLDL)-induced tumor necrosis factor alpha and monocyte chemoattractant protein 1 expression by suppressing nuclear factor-kappaB phosphorylation and nuclear translocation in RAW 264.7 macrophages. Treatment with gCTRP9 strikingly increased the level of phosphorylated adenosine monophosphate-activated protein kinase (AMPK). AMPK inhibitor abolished the anti inflammatory effects of gCTRP9. Moreover, gCTRP9 increased the expression of adiponectin receptor 1 (AdipoR1). Downregulation of AdipoR1 by siRNA could abrogate the activation of AMPK and the anti-inflammatory effects of gCTRP9. These results suggested that gCTRP9 protected RAW 264.7 macrophages from oxLDL via AMPK activation in an AdipoR1 dependent fashion. PMID- 27188184 TI - Combined effect of astaxanthin and squalene on oxidative stress in vivo. AB - Obesity and diabetes, risk factors for metabolic syndrome, are characterized by oxidative stress and inflammatory responses. Marine biofunctionals, astaxanthin (Ax) and squalene (SQ), were evaluated for their combined effect. Groups of male KK-A (y) mice were fed high fat/sucrose diet for 4 weeks, supplemented with either 0.1 %Ax, 2 %SQ or 0.1 %Ax + 2 %SQ. In comparison to control, Sod was elevated in only Ax + SQ. However, Gpx was highest in Ax + SQ, indicating the combined antioxidant effect of Ax and SQ. This was supported by elevated mRNA expression of Sod1 and Gpx1. Except adiponectin (elevated in Ax and Ax + SQ), expression of other inflammatory markers was not altered. Blood glucose levels were decreased in SQ and Ax + SQ while liver triglycerides decreased in SQ group. This is the first in vivo study demonstrating combined effects of Ax and SQ resulting in antioxidant effects and modulation of glucose/triglyceride levels. This study highlights the benefit of utilizing Ax and SQ together for management of obesity/diabetes. PMID- 27188187 TI - Albert L Rhoton Jr. PMID- 27188185 TI - Design, Synthesis and Qualitative Structure Activity Relationship Evaluations of Quinoline-Based Bisarylimidazoles as Antibacterial Motifs. AB - BACKGROUND: The emergence of drug-resistant bacteria in clinical practice has propelled a concerted effort to find new classes of antibiotics that will circumvent current modes of resistance. We previously described a set of imidazopyridine antibacterial leads that contain a core composed of benzimidazole and a central phthalic acid linker. These compounds showed potent antibacterial properties against a wide range of Gram-positive and Gram-negative bacteria. In this respect, we conducted a systematic exploration of new disubstituted imidazole functionalities on quinoline 4-position as the central linker, to determine the factors that direct the potent antibacterial activity. We found that some of the newly synthesized compounds possessed more potent activity compared to currently available medications. The newly synthesized compounds were screened against several clinical isolates and Staphylococcus aureus, including the methicillinresistant (MRSA) and the methicillin-sensitive (MSAA). METHODS: The goal of this work is to undertake rigorous testing of new hybrid scaffolds of quinoline flanked by diaryl imidazoles and their structure-activity against a range of bacterial strains. Described herein is the account of the modification of the central linker region, the imidazole functionality, and substituents at the 4-position of the quinoline, and their effect on the antibacterial potency of the resulting derivatives. Our efforts here have been driven by previous reports on the applications of Pfitzinger cyclization protocol. This complexity generating reaction transforms a relatively simple substrate, into a more complex products with the potential for diversification via functionalization of the resultant acid. RESULTS: We identified compounds that possess potent and broad spectrum antibacterial activities against clinical isolates and drug resistant strains. Structure-Activity relationships of these compounds were further explored to determine the crucial structural features needed to enhance their antibacterial activity. In this respect, it was found that, hydrophobic and electron-withdrawing moieties, such as halogens, were required on each end of the isoquinoline-based bisaryl imidazole hybrid motifs to produce broad-spectrum activity against the tested strains. Thus, molecules containing halophenyl or pyridyl arms were found more potent than molecules containing thiophene and/or electron-releasing groups on the phenyl arms, which showed much less antibacterial activity against the tested strains. CONCLUSION: In summary, 4-(4,5 diphenyl-1H-imidazol-2-yl)-2-phenylquinoline systems can be assembled efficiently through the Pfitzinger ring expansion- condensation strategy. This approach appears to hold considerable synthetic utility. The particular value of such a synthetic route resides on the conciseness and efficiency through which imidazo quinoline construction can be synthesized from structurally simple and accessible acetophenone precursors. PMID- 27188188 TI - Biventricular Circulatory Support Using 2 Axial Flow Catheters for Cardiogenic Shock Without the Need for Surgical Vascular Access. PMID- 27188186 TI - Impact of incident diabetes on atherosclerotic cardiovascular disease according to statin use history among postmenopausal women. AB - To compare impact of incident diabetes on atherosclerotic cardiovascular disease (ASCVD) risk among postmenopausal women according to statin use. Prospective data from 120,499 postmenopausal women without prevalent diabetes or cardiovascular disease at baseline from the Women's Health Initiative were used. Incident diabetes was self-reported annually and defined as treatment with pills or injectable medication for diabetes. Current statin use was determined at enrollment and years 1, 3, 6, 9 and 13.5 in the three clinical trial arms, and at baseline, year 3, and 13.5 for the observational study. The primary outcome was incident ASCVD events, self-reported annually and adjudicated by blinded local and central physicians. Incident diabetes and statin use status were fitted as time-varying covariates in Cox regression models to assess ASCVD risk during an average follow-up of 13.6 years. For those not on statins at the time of diabetes diagnosis, there was a 42 % increased risk of ASCVD [hazard ratio (HR) 1.42, 95 % CI 1.28-1.58] among women with incident diabetes versus those without diabetes. Among women on statins, there was a 39 % increased risk of ASCVD (HR 1.39, 95 % CI 1.12-1.74) in women with incident diabetes versus those without diabetes. The increased ASCVD risk due to diabetes was similar between women before or after initiating statins (P = 0.89). Whether diabetes was diagnosed before or after statin use did not alter the increased risk of ASCVD associated with diabetes. Mitigating the increased incidence of diabetes in statin users could increase the ASCVD benefit-to-risk ratio of statins. PMID- 27188189 TI - Communication and Shared Understanding Between Parents and Resident-Physicians at Night. AB - BACKGROUND AND OBJECTIVE: Communication breakdowns between members of the health care team compromise patient safety and experience. Communication breakdowns with parents, an important but often overlooked part of the health care team, are understudied. Parents may play a particularly important role in nighttime care given decreased staffing and inadequate transitions of care at night. We studied communication breakdowns evidenced by lack of shared understanding between parents and night-team residents about the reason for admission and care plan. METHODS: We conducted a prospective cohort study of parents (n = 286) and night team senior residents (n = 34) from May 1, 2013 to October 31, 2013. Parents and residents rated communication and described patients' reason for admission, overall plan, and overnight plan. Two physician investigators independently reviewed (kappa = 0.63) resident-parent dyads, assigned subsequently dichotomized 4-point overall agreement scores, and rated plan complexity. Using clustered logistic regression, we evaluated relationships among demographics, plan complexity, and shared understanding. We also examined resident and parent perceptions of shared understanding. RESULTS: We analyzed data from 257 parent resident dyads. Among these, 45.1% were rated as lacking shared understanding (agreement score = 1 or 2). In multivariate analysis, higher plan complexity (P < .001) and length of stay (P = .002) were associated with lack of shared understanding; lower parental education was a borderline predictor (P = .05). When surveyed, parents and residents reported that they shared an understanding with one another about care plans in 86.0% and 73.1% of cases, respectively. CONCLUSIONS: Parents and night-team residents frequently lack shared understanding. Family-centered care initiatives to improve parent-provider communication and shared understanding may help empower parents as partners in safe and high-quality nighttime care. PMID- 27188191 TI - Molecular identification and functional characteristics of peptide transporters in the bonnethead shark (Sphyrna tiburo). AB - Elasmobranchs are considered to be top marine predators, and in general play important roles in the transfer of energy within marine ecosystems. Despite this, little is known regarding the physiological processes of digestion and nutrient absorption in these fishes. One topic that is particularly understudied is the process of nutrient uptake across the elasmobranch gastrointestinal tract. Given their carnivorous diet, the present study sought to expand knowledge on dietary nutrient uptake in elasmobranchs by focusing on the uptake of products of protein digestion. To accomplish this, a full-length cDNA encoding peptide transporter 1 (PepT1), a protein previously identified within the brush border membrane of vertebrates that is responsible for the translocation of peptides released during digestion by luminal and membrane-bound proteases, was isolated from the bonnethead shark (Sphyrna tiburo). A cDNA encoding the related peptide transporter PepT2 was also isolated from S. tiburo using the same methodology. The presence of PepT1 was then localized in multiple components of the bonnethead digestive tract (esophagus, stomach, duodenum, intestine, rectum, and pancreas) using immunohistochemistry. Vesicle studies were used to identify the apparent affinity of PepT1 and to quantify the rate of dipeptide uptake by its H(+) dependent cotransporter properties. The results of this study provide insight into the properties of peptide uptake within the bonnethead gut, and can facilitate future work on physiological regulation of protein metabolism and absorption including how these processes may vary in elasmobranchs that exhibit different feeding strategies. PMID- 27188192 TI - Innate immunity and testosterone rapidly respond to acute stress, but is corticosterone at the helm? AB - When faced with a stressor, vertebrates can rapidly increase the secretion of glucocorticoids, which is thought to improve the chances of survival. Concurrent changes in other physiological systems, such as the reproductive endocrine or innate immune systems, have received less attention, particularly in wild vertebrates. It is often thought that glucocorticoids directly modulate immune performance during a stress response, but, in many species, androgens also rapidly respond to stress. However, to our knowledge, no study has simultaneously examined the interactions between the glucocorticoid, androgen, and innate immune responses to stress in a wild vertebrate. To address this issue, we tested the hypothesis that the change in plasma corticosterone (CORT) in response to the acute stress of capture and restraint is correlated with the concurrent changes in plasma testosterone (T) and innate immune performance (estimated by the capacity of plasma to agglutinate and lyse foreign cells) in the Abert's Towhee (Melozone aberti). Furthermore, to broaden the generality of the findings, we compared male and female towhees, as well as males from urban and non-urban populations. Acute stress increased plasma CORT, decreased plasma T in males, and decreased innate immune performance, but the increase in CORT during stress was not correlated with the corresponding decreases in either plasma T or innate immunity. By contrast, the plasma T stress response was positively correlated with the innate immune stress response. Collectively, our results challenge the proposition that the glucocorticoid stress response is correlated with the concurrent changes in plasma T, a key reproductive hormone, and innate immunity, as estimated by agglutination and lysis. PMID- 27188193 TI - The association between symptoms of sexual dysfunction and age at onset in Parkinson's disease. AB - OBJECTIVE: Age at onset in Parkinson's disease (PD) seems to be related nonmotor symptoms. In this study we investigated the effect of the age at onset on symptoms of sexual dysfunction (SSD) in patients with PD. METHODS: This prospective study comprised 22 consecutive outpatients with early onset PD (EOPD onset of the disease before 55 years), and 66 outpatients with late onset PD (LOPD-onset of PD over 55 years). They were all recruited from the Department of Movement Disorders, Clinic of Neurology. The diagnosis was established according to the UK PD Brain Bank Criteria by a movement disorders specialist. The Unified PD Rating Scale (UPDRS) motor was used to assess motor disability and Hoehn and Yahr (H&Y) stage was used to establish disease severity. The sexual functions of the patients were rated by applying the Arizona Sexual Experiences Scale (ASEX). RESULTS: Thirteen EOPD patients (59.09 %) and 53 of the LOPD patients (80.3 %) (p 0.047) reported dissatisfaction with at least one item of ASEX. There were no differences between H&Y stages (p 0.205) UPDRS total (p 0.267) and motor scores (p 0.100) between groups. LOPD patients had significantly higher ASEX scores than EOPD patients (p 0.001). INTERPRETATION: Sexual dysfunciton occurs more frequently and more severely in LOPD than EOPD patients. PD patients with different ages at onset clinically present differently in terms of SSD. PMID- 27188194 TI - Authentication of the botanical origin of Western herbal products using Cimicifuga and Vitex products as examples. AB - Various herbal medicines have been developed and used in various parts of the world for thousands of years. Although locally grown indigenous plants were originally used for traditional herbal preparations, Western herbal products are now becoming popular in Japan with the increasing interest in health. At the same time, there are growing concerns about the substitution of ingredients and adulteration of herbal products, highlighting the need for the authentication of the origin of plants used in herbal products. This review describes studies on Cimicifuga and Vitex products developed in Europe and Japan, focusing on establishing analytical methods to evaluate the origins of material plants and finished products. These methods include a polymerase chain reaction-restriction fragment length polymorphism method and a multiplex amplification refractory mutation system method. A genome-based authentication method and liquid chromatography-mass spectrometry-based authentication for black cohosh products, and the identification of two characteristic diterpenes of agnus castus fruit and a shrub chaste tree fruit-specific triterpene derivative are also described. PMID- 27188197 TI - Erratum to: The Affordable Care Act and integrated behavioral health programs in community health centers to promote utilization of mental health services among Asian Americans. PMID- 27188196 TI - The Affordable Care Act and integrated behavioral health programs in community health centers to promote utilization of mental health services among Asian Americans. AB - The Affordable Care Act has greatly expanded health care coverage and recognizes mental health as a major priority. However, individuals suffering from mental health disorders still face layered barriers to receiving health care, especially Asian Americans. Integration of behavioral health services within primary care is a viable way of addressing underutilization of mental health services. This paper provides insight into a comprehensive care approach integrating behavioral health services into primary care to address underutilization of mental health services in the Asian American population. True integration of behavioral health services into primary care will require financial support and payment reform to address multi-disciplinary care needs and optimize care coordination, as well as training and workforce development early in medical and mental health training programs to develop the skills that aid prevention, early identification, and intervention. Funding research on evidence-based practice oriented to the Asian American population needs to continue. PMID- 27188195 TI - Resistant Hypertension: An Incurable Disease or Just a Challenge For Our Medical Skill? AB - Resistant hypertension is classically defined as a clinical condition in which target blood pressure values of 140/90 mmHg are not achieved despite an optimal pharmacological therapy of at least three antihypertensive drugs, including a diuretic. The aim of this review is to give an outline of the nosography of this disorder, highlighting the differences between true and apparent resistant hypertension. Since the proportions of patients who can be defined as resistant to antihypertensive treatment is elevated, this distinction is mandatory in order to identify only those who need special clinical attention and, possibly, newer non-traditional techniques. While at first glance resistant hypertension may appear as an insuperable problem, an accurate clinical work-up of these patients, aimed at excluding reversible causes and optimizing pharmacological treatment, represents an effective solution in most cases. PMID- 27188198 TI - Irinotecan Monotherapy Versus Irinotecan-Based Combination as Second-Line Chemotherapy in Advanced Gastric Cancer: A Meta-Analysis. AB - PURPOSE: A meta-analysis was conducted to examine the question of whether combination regimens are more effective than monotherapy as a second-line chemotherapy in advanced gastric cancer. MATERIALS AND METHODS: The MEDLINE and the EMBASE databases and the Cochrane Central Register for Controlled Trials were searched using appropriate keywords. Only randomized controlled trials were eligible. RESULTS: Taxane-based study is rare; thus, four irinotecan-based studies were finally included in the meta-analysis. Out of 661 patients, 331 patients were assigned to combination therapy and 330 to monotherapy. Cisplatin or fluoropyrimidine (S-1 or 5-fluorouracil) was used as a combination partner to irinotecan. The pooled hazard ratio (HR) for overall survival (OS) and for progression-free survival (PFS) was 0.938 (95% confidence interval [CI], 0.796 to 1.104; p=0.442) and 0.815 (95% CI, 0.693 to 0.958; p=0.013). In subgroup analysis according to previous exposure to a partner agent, the PFS benefit of combination was observed only in the partially exposed group (HR, 0.784; 95% CI, 0.628 to 0.980; p=0.032). CONCLUSION: Second-line irinotecan-based combination was not associated with increased OS, but with PFS benefit, which seemed particularly significant for patients receiving combination with a new agent. PMID- 27188199 TI - Post-bevacizumab Clinical Outcomes and the Impact of Early Discontinuation of Bevacizumab in Patients with Recurrent Malignant Glioma. AB - PURPOSE: Bevacizumab+/-irinotecan is effective for treatment of recurrent malignant gliomas. However, the optimal duration of treatment has not been established. MATERIALS AND METHODS: Ninety-four consecutive patients with recurrent malignant glioma who were treated with bevacizumab at our institutions were identified. Patients who continued bevacizumab until tumor progression were enrolled in a late discontinuation (LD) group, while those who stopped bevacizumab before tumor progression were enrolled in an early discontinuation (ED) group. Landmark analyses were performed at weeks 9, 18, and 26 for comparison of patient survival between the two groups. RESULTS: Among 89 assessable patients, 62 (69.7%) and 27 (30.3%) patients were categorized as the LD and ED groups, respectively. According to landmark analysis, survival times from weeks 9, 18, and 26 were not significantly different between the two groups in the overall population. However, the LD group showed a trend toward increased survival compared to the ED group among responders. In the ED group, the median time from discontinuation to disease progression was 11.4 weeks, and none of the patients showed a definite rebound phenomenon. Similar median survival times after disease progression were observed between groups (14.4 weeks vs. 15.7 weeks, p=0.251). Of 83 patients, 38 (45.8%) received further therapy at progression, and those who received further therapy showed longer survival in both the LD and ED groups. CONCLUSION: In recurrent malignant glioma, duration of bevacizumab was not associated with survival time in the overall population. However, ED of bevacizumab in responding patients might be associated with decreased survival. PMID- 27188200 TI - Estimation of the Incidence of Hepatocellular Carcinoma and Cholangiocarcinoma in Songkhla, Thailand, 1989-2013, Using Multiple Imputation Method. AB - PURPOSE: Histological specimens are not required for diagnosis of liver and bile duct (LBD) cancer, resulting in a high percentage of unknown histologies. We compared estimates of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) incidences by imputing these unknown histologies. MATERIALS AND METHODS: A retrospective study was conducted using data from the Songkhla Cancer Registry, southern Thailand, from 1989 to 2013. Multivariate imputation by chained equations (mice) was used in re-classification of the unknown histologies. Age standardized rates (ASR) of HCC and CCA by sex were calculated and the trends were compared. RESULTS: Of 2,387 LBD cases, 61% had unknown histology. After imputation, the ASR of HCC in males during 1989 to 2007 increased from 4 to 10 per 100,000 and then decreased after 2007. The ASR of CCA increased from 2 to 5.5 per 100,000, and the ASR of HCC in females decreased from 1.5 in 2009 to 1.3 in 2013 and that of CCA increased from less than 1 to 1.9 per 100,000 by 2013. RESULTS: of complete case analysis showed somewhat similar, although less dramatic, trends. CONCLUSION: In Songkhla, the incidence of CCA appears to be stable after increasing for 20 years whereas the incidence of HCC is now declining. The decline in incidence of HCC among males since 2007 is probably due to implementation of the hepatitis B virus vaccine in the 1990s. The rise in incidence of CCA is a concern and highlights the need for case control studies to elucidate the risk factors. PMID- 27188202 TI - Use of a Combined Gene Expression Profile in Implementing a Drug Sensitivity Predictive Model for Breast Cancer. AB - PURPOSE: Chemotherapy targets all rapidly growing cells, not only cancer cells, and thus is often associated with unpleasant side effects. Therefore, examination of the chemosensitivity based on genotypes is needed in order to reduce the side effects. MATERIALS AND METHODS: Various computational approaches have been proposed for predicting chemosensitivity based on gene expression profiles. A linear regression model can be used to predict the response of cancer cells to chemotherapeutic drugs, based on genomic features of the cells, and appropriate sample size for this method depends on the number of predictors. We used principal component analysis and identified a combined gene expression profile to reduce the number of predictors. RESULTS: The coefficients of determinanation (R2) of prediction models with combined gene expression and several independent gene expressions were similar. Corresponding F values, which represent model significances were improved by use of a combined gene expression profile, indicating that the use of a combined gene expression profile is helpful in predicting drug sensitivity. Even better, a prediction model can be used even with small samples because of the reduced number of predictors. CONCLUSION: Combined gene expression analysis is expected to contribute to more personalized management of breast cancer cases by enabling more effective targeting of existing therapies. This procedure for identifying a cell-type-specific gene expression profile can be extended to other chemotherapeutic treatments and many other heterogeneous cancer types. PMID- 27188201 TI - Reactive Oxygen Species Modulator 1 (Romo1) Predicts Poor Outcomes in Advanced Non-small Cell Lung Cancer Patients Treated with Platinum-Based Chemotherapy. AB - PURPOSE: Reactive oxygen species modulator 1 (Romo1) is a key mediator of intracellular reactive oxygen species production. However, examination of the clinical usefulness of Romo1 in cancers has been limited. We evaluated the association of Romo1 expression with clinical outcomes in advanced non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy. MATERIALS AND METHODS: Romo1 expression in tumor tissue was examined by immunohistochemistry and evaluated by histological score. Survival analyses were performed according to Romo1 expression and the association between Romo1 expression and clinical parameters was evaluated. RESULTS: A total of 88 tumor specimens were analyzed. Significantly shorter median progression-free survival (PFS) was observed in the high Romo1 group compared with the low Romo1 group (4.5 months vs. 9.8 months, p < 0.001), and the median overall survival (OS) of the high Romo1 group was also significantly shorter than that of the low Romo1 group (8.4 months vs. 15.5 months, p < 0.001). Results of multivariate analyses showed significant association of high Romo1 expression with both poor PFS (hazard ratio [HR], 2.75; 95% confidence interval [CI], 1.71 to 4.44) and poor OS (HR, 3.99; 95% CI, 2.36 to 6.74). Results of the subgroup analysis showed a similar association regardless of tumor histology. Romo1 expression showed no association with any clinical parameter including age, sex, smoking status, stage, differentiation, or tumor histology. CONCLUSION: Romo1 overexpression was associated with poor response to treatment and shorter survival in advanced NSCLC patients treated with platinum-based chemotherapy. Romo1 could be a potential adverse predictive marker in this setting. PMID- 27188204 TI - Comparison of Total Body Irradiation (TBI) Conditioning with Non-TBI for Autologous Stem Cell Transplantation in Newly Diagnosed or Relapsed Mature T- and NK-Cell Non-Hodgkin Lymphoma. AB - PURPOSE: This retrospective study was conducted for comparison of survival outcomes and toxicities of autologous stem cell transplantation (ASCT) based on the use of total body irradiation (TBI) as a part of the conditioning regimen in patients with mature T- and natural killer (NK)-cell lymphomas. MATERIALS AND METHODS: Patients who underwent ASCT in the upfront or salvage setting between January 2000 and December 2013 were analyzed. Patients were dichotomized according to the TBI group (n=38) and non-TBI group (n=60) based on the type of conditioning regimen for ASCT. RESULTS: Patients with responsive disease underwent upfront ASCT (TBI, n=16; non-TBI, n=29) whereas patients with refractory disease (TBI, n=9; non-TBI, n=12) or relapsed disease (TBI, n=13; non TBI, n=19) underwent ASCT after salvage treatment. Hematologic and non hematologic toxicities were manageable, and the median cumulative toxicity score according to Seattle criteria was estimated as 2 (range, 0 to 7) in both groups. No significant difference in 100-day mortality was observed between the TBI (13%, 5/38) and non-TBI (12%, 12/60) groups, and most deaths were related to disease progression. There was no difference in overall and progression-free survival; however, the TBI group showed a trend of better survival in upfront and salvage ASCT than the non-TBI group. However, patients with refractory disease showed the worst outcome regardless of the use of TBI. Patients who showed complete response before ASCT showed better progression-free survival than thosewho showed partial response. CONCLUSION: TBI could be used as an effective part of conditioning for ASCT in patients with mature T- and NK-cell lymphomas. PMID- 27188203 TI - Curative Resection for Metachronous Pulmonary Metastases from Colorectal Cancer: Analysis of Survival Rates and Prognostic Factors. AB - PURPOSE: Prognostic factors in patients with pulmonary metastases (PM) from colorectal cancer (CRC) are still controversial. This study assessed oncologic outcomes and prognostic factors in patients with metachronous PM from CRC. MATERIALS AND METHODS: Between June 2003 and December 2011, 122 patients with CRC underwent curative resection of PM detected at least 4 months after CRC resection. Clinico-pathological factors selected from the prospectively maintained database were analyzed retrospectively. RESULTS: The median disease free interval (DFI) between resection of the primary tumor and detection of PM was 22.0 months (range, 4 to 85 months). Solitary PM were detected in 77 patients (63.1%), with a median maximal tumor diameter of 12.0 mm (range, 2 to 70 mm). Of 52 patients who underwent mediastinal lymph node (LN) dissection, eight patients had LN involvement. Five-year overall survival and disease-free survival (DFS) rates after initial pulmonary metastasectomy were 66.4% and 50.9%, respectively. DFI, mediastinal LN involvement, and the number and distribution of PM were significantly prognostic factors for DFS. In multivariable analysis DFI >= 12 months, solitary lesion, and absence of mediastinal LN involvement were independently prognostic for DFS. Of the 122 patients, 48 patients (39.3%) developed recurrent PM a median 13.0 months after initial pulmonary metastasectomy. Recurrent DFI was independently prognostic of DFS in patients who underwent repeated pulmonary metastasectomy. CONCLUSION: There is a potential survival benefit for patients with metachronous PM from CRC who undergo pulmonary metastasectomy, even those with recurrent PM. Pulmonary metastasectomy should be considered in selected patients, particularly those with longer DFI, solitary lesions, and absence of mediastinal LN involvement. PMID- 27188207 TI - Promoting the occupations of parents of children with disability in early childhood intervention services - Building stronger families and communities. PMID- 27188205 TI - Anti-proliferative Effect of Engineered Neural Stem Cells Expressing Cytosine Deaminase and Interferon-beta against Lymph Node-Derived Metastatic Colorectal Adenocarcinoma in Cellular and Xenograft Mouse Models. AB - PURPOSE: Genetically engineered stem cells may be advantageous for gene therapy against various human cancers due to their inherent tumor-tropic properties. In this study, genetically engineered human neural stem cells (HB1.F3) expressing Escherichia coli cytosine deaminase (CD) (HB1.F3.CD) and human interferon-beta (IFN-beta) (HB1.F3.CD.IFN-beta) were employed against lymph node-derived metastatic colorectal adenocarcinoma. MATERIALS AND METHODS: CD can convert a prodrug, 5-fluorocytosine (5-FC), to active 5-fluorouracil, which inhibits tumor growth through the inhibition of DNA synthesis,while IFN-beta also strongly inhibits tumor growth by inducing the apoptotic process. In reverse transcription polymerase chain reaction analysis, we confirmed that HB1.F3.CD cells expressed the CD gene and HB1.F3.CD.IFN-beta cells expressed both CD and IFN-beta genes. RESULTS: In results of a modified trans-well migration assay, HB1.F3.CD and HB1.F3.CD.IFN-beta cells selectively migrated toward SW-620, human lymph node derived metastatic colorectal adenocarcinoma cells. The viability of SW-620 cells was significantly reduced when co-cultured with HB1.F3.CD or HB1.F3.CD.IFN-beta cells in the presence of 5-FC. In addition, it was found that the tumor-tropic properties of these engineered human neural stem cells (hNSCs) were attributed to chemoattractant molecules including stromal cell-derived factor 1, c-Kit, urokinase receptor, urokinase-type plasminogen activator, and C-C chemokine receptor type 2 secreted by SW-620 cells. In a xenograft mouse model, treatment with hNSC resulted in significantly inhibited growth of the tumor mass without virulent effects on the animals. CONCLUSION: The current results indicate that engineered hNSCs and a prodrug treatment inhibited the growth of SW-620 cells. Therefore, hNSC therapy may be a clinically effective tool for the treatment of lymph node metastatic colorectal cancer. PMID- 27188206 TI - A Phase II Study of Poziotinib in Patients with Epidermal Growth Factor Receptor (EGFR)-Mutant Lung Adenocarcinoma Who Have Acquired Resistance to EGFR-Tyrosine Kinase Inhibitors. AB - PURPOSE: We examined the efficacy of poziotinib, a second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) in patients with lung adenocarcinoma with activating EGFR mutations, who developed acquired resistance (AR) to EGFR-TKIs. MATERIALS AND METHODS: This single-arm phase II study included EGFR-mutant lung adenocarcinoma with AR to erlotinib or gefitinib based on the Jackman criteria. Patients received poziotinib 16 mg orally once daily in a 28-day cycle. The primary endpoint was progression-free survival (PFS). Prestudy tumor biopsies and blood samples were obtained to determine resistance mechanisms. RESULTS: Thirty-nine patients were treated. Tumor genotyping was determined in 37 patients; 19 EGFR T790M mutations and two PIK3CA mutations were detected in the prestudy tumors, and seven T790M mutations were detected in the plasma assay. Three (8%; 95% confidence interval [CI], 2 to 21) and 17 (44%; 95% CI, 28 to 60) patients had partial response and stable disease, respectively. The median PFS and overall survival were 2.7 months (95% CI, 1.8 to 3.7) and 15.0 months (95% CI, 9.5 to not estimable), respectively. A longer PFS was observed for patients without T790M or PIK3CA mutations in tumor or plasma compared to those with these mutations (5.5 months vs. 1.8 months, p=0.003). The most frequent grade 3 adverse events were rash (59%), mucosal inflammation (26%), and stomatitis (18%). Most patients required one (n=15) or two (n=15) dose reductions. CONCLUSION: Low activity of poziotinib was detected in patients with EGFR-mutant non-small cell lung cancer who developed AR to gefitinib or erlotinib, potentially because of severe-toxicityimposed dose limitation. PMID- 27188208 TI - HTLV-1-associated myelopathy/tropical spastic paraparesis. AB - Human T-lymphotropic virus 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive disease of the CNS that causes weakness or paralysis of the legs, lower back pain and urinary symptoms. HAM/TSP was first described in Jamaica in the nineteenth century, but the aetiology of the condition, infection with the retrovirus HTLV-1, was only identified in the 1980s. HAM/TSP causes chronic disability and, accordingly, imposes a substantial health burden in areas where HTLV-1 infection is endemic. Since the discovery of the cause of HAM/TSP, considerable advances have been made in the understanding of the virology, immunology, cell biology and pathology of HTLV-1 infection and its associated diseases. However, progress has been limited by the lack of accurate animal models of the disease. Moreover, the treatment of HAM/TSP remains highly unsatisfactory: antiretroviral drugs have little impact on the infection and, although potential disease-modifying therapies are widely used, their value is unproved. At present, clinical management is focused on symptomatic treatment and counselling. Here, we summarize current knowledge on the epidemiology, pathogenesis and treatment of HAM/TSP and identify areas in which further research is needed. For an illustrated summary of this Primer, visit: http://go.nature.com/tjZCFM. PMID- 27188209 TI - Assessment of the priority target group of mental health service networks within a nation-wide reform of adult psychiatry in Belgium. AB - BACKGROUND: Belgium is currently implementing a nation-wide reform of mental health care delivery based on service networks. These networks are supposed to strengthen the community-based supply of care, reduce the resort to hospitals, and improve the continuity of care. They are also intended to supply comprehensive care to all adult mental health users. It is unclear, however, if one single model of network can target the needs of the whole adult population with mental health problems. METHODS: In 2011, ten networks were commissioned and assessed. Networks included a total of 635 services of different types. Services were asked to select 10 users by systematic sampling and to state whether these users were considered as a priority for care in the network. Sociodemographic, social integration level, diagnoses, and psycho-social functioning variables were also collected. RESULTS: Two thousand four hundred ninety users were included, and 1564 were given priority for network care. Priority was higher for men than for women (69.9 % versus 56.2 %), and for non-nationals than for Belgians (72.6 % versus 61.9 %). Users were designated priority when they had poor psycho-social functioning (HoNOS > 17, OR = 3.15, p < 0.001), personality disorder or schizophrenia (OR = 1.54, p < 0.001), and a medium level of social integration (SIX = [2,3], OR = 1.57, p < 0.001). Less socially integrated patients (SIX < 1, OR = 0.53, p < 0.001) and users of community and social services were less likely to be selected. CONCLUSION: Although the reform was intended for the whole population of adults with mental health problems, the users selected have a profile of severe mentally-ill users with social deprivation and poor social functioning. Policy may have been over-ambitious trying to address the whole population with one single type of service network. The actual selection process of users makes it less likely that the reform will achieve all its objectives. PMID- 27188211 TI - Chemical vapor deposition of MoS2 layers from Mo-S-C-O-H system: thermodynamic modeling and validation. AB - A detailed thermodynamic analysis of the solid and gas phases of the Mo-S-C-O-H system used for large area chemical vapor deposition (CVD) of MoS2 is presented and compared with experimental results. Given the multivariable nature of the problem, excellent agreement is observed. Deviations, observed from thermodynamic predictions, mainly at low temperatures and high flow rates have been highlighted and discussed. CVD phase diagrams which predict parameter windows in which pure MoS2 can be synthesized have been provided for important gas phase chemistries. Pure H2 as a carrier gas is shown to facilitate the largest contamination free process window. CO presence is shown to significantly reduce the nucleation rate and enable large island sizes but at the cost of carbon contamination. Oxygen leaks are shown to result in sulphur contamination. The absence of H2S during cooling is shown to yield Mo due to the reduction of MoS2 by hydrogen. Oxidation of Mo causes oxide contamination. PMID- 27188210 TI - Compact quantum dot-antibody conjugates for FRET immunoassays with subnanomolar detection limits. AB - A novel two-step approach for quantum dot (QD) functionalization and bioconjugation is presented, which yields ultra-compact, stable, and highly luminescent antibody-QD conjugates suitable for use in FRET immunoassays. Hydrophobic InPZnS/ZnSe/ZnS (emission wavelength: 530 nm), CdSe/ZnS (605 nm), and CdSeTe/ZnS (705 nm) QDs were surface functionalized with zwitterionic penicillamine, enabling aqueous phase transfer under conservation of the photoluminescence properties. Post-functionalization with a heterobifunctional crosslinker, containing a lipoic acid group and a maleimide function, enabled the subsequent coupling to sulfhydryl groups of proteins. This was demonstrated by QD conjugation with fragmented antibodies (F(ab)). The obtained F(ab)-QD conjugates range among the smallest antibody-functionalized nanoprobes ever reported, with a hydrodynamic diameter <13 nm, PL quantum yield up to 66% at 705 nm, and colloidal stability of several months in various buffers. They were applied as FRET acceptors in homogeneous, time-gated immunoassays using Tb-antibodies as FRET donors, both coupled by an immunological sandwich complex between the two antibodies and a PSA (prostate specific antigen) biomarker. The advantages of the compact surface coating for FRET could be demonstrated by an 6.2 and 2.5 fold improvement of the limit of detection (LOD) for PSA compared to commercially available hydrophilic QDs emitting at 605 and 705 nm, respectively. While the commercial QDs contain identical inorganic cores responsible for their fluorescence, they are coated with a comparably thick amphiphilic polymer layer leading to much larger hydrodynamic diameters (>26 nm without biomolecules). The LODs of 0.8 and 3.7 ng mL(-1) obtained in 50 MUL serum samples are below the clinical cut-off level of PSA (4 ng mL(-1)) and demonstrate their direct applicability in clinical diagnostics. PMID- 27188212 TI - Opposing effects of actin signaling and LFA-1 on establishing the affinity threshold for inducing effector T-cell responses in mice. AB - Mature CD8(+) T cells use a narrow antigen affinity threshold to generate tissue infiltrating cytotoxic effector T cells and induce autoimmune pathology, but the mechanisms that establish this antigen affinity threshold are poorly understood. Only antigens with affinities above the threshold induce stable contacts with APCs, polarization of a T cell, and asymmetric T-cell division. Previously published data indicate that LFA-1 inside-out signaling might be involved in establishing the antigen affinity threshold. Here, we show that subthreshold antigens weakly activate all major distal TCR signaling pathways. Low-affinity antigens are more dependent on LFA-1 than suprathreshold antigens. Moreover, augmenting the inside-out signaling by hyperactive Rap1 does not increase responses to the subthreshold antigens. Thus, LFA-1 signaling does not contribute to the affinity-based antigen discrimination. However, we found that subthreshold antigens do not induce actin rearrangement toward an APC, mediated by Rho-family GTPases, Cdc42, and Rac. Our data suggest that Rac and Cdc42 contribute to the establishment of the antigen affinity threshold in CD8(+) T cells by enhancing responses to high-affinity antigens, or by reducing the responses to low-affinity antigens. PMID- 27188213 TI - Ferric ions accumulate in the walls of metabolically inactivating Saccharomyces cerevisiae cells and are reductively mobilized during reactivation. AB - Mossbauer and EPR spectra of fermenting yeast cells before and after cell wall (CW) digestion revealed that CWs accumulated iron as cells transitioned from exponential to post-exponential growth. Most CW iron was mononuclear nonheme high spin (NHHS) Fe(III), some was diamagnetic and some was superparamagnetic. A significant portion of CW Fe was removable by EDTA. Simulations using an ordinary differential-equations-based model suggested that cells accumulate Fe as they become metabolically inactive. When dormant Fe-loaded cells were metabolically reactivated in Fe-deficient bathophenanthroline disulfonate (BPS)-treated medium, they grew using Fe that had been mobilized from their CWs AND using trace amounts of Fe in the Fe-deficient medium. When grown in Fe-deficient medium, Fe-starved cells contained the lowest cellular Fe concentrations reported for a eukaryotic cell. During metabolic reactivation of Fe-loaded dormant cells, Fe(III) ions in the CWs of these cells were mobilized by reduction to Fe(II), followed by release from the CW and reimport into the cell. BPS short-circuited this process by chelating mobilized and released Fe(II) ions before reimport; the resulting Fe(II)(BPS)3 complex adsorbed on the cell surface. NHHS Fe(II) ions appeared transiently during mobilization, suggesting that these ions were intermediates in this process. In the presence of chelators and at high pH, metabolically inactive cells leached CW Fe; this phenomenon probably differs from metabolic mobilization. The iron regulon, as reported by Fet3p levels, was not expressed during post-exponential conditions; Fet3p was maximally expressed in exponentially growing cells. Decreased expression of the iron regulon and metabolic decline combine to promote CW Fe accumulation. PMID- 27188214 TI - Platelet-rich plasma therapy: another appealing technology for regenerative medicine? PMID- 27188215 TI - Analysis of terms used for the diagnosis and classification of amyotrophic lateral sclerosis and motor neuron disease. AB - There is no test for amyotrophic lateral sclerosis (ALS) and so attempts have been made to produce standardized diagnostic criteria based on clinical and electrophysiological findings, e.g. El Escorial. However, the phenotypic classification of the subtypes of ALS is also based on clinical features leading to conflation of diagnosis and phenotype. We used a five-question online survey with ALS specialists to explore the range of descriptors and how they are used. Of 101 specialists approached, 72 completed the survey. The most frequently used labels were 'ALS', 'PLS' and 'familial'. Labels other than the El Escorial categories were mainly used as clinical descriptors (83%). Approximately 50% of respondents recorded that the El Escorial criteria had no useful role in patient discussion or in the diagnostic process. Only 31% of respondents rated their current classification system above the median for being logical. A more rational system explicitly distinguishing diagnostic and phenotypic criteria is essential. PMID- 27188216 TI - Emodin: A Review of its Pharmacology, Toxicity and Pharmacokinetics. AB - Emodin is a natural anthraquinone derivative that occurs in many widely used Chinese medicinal herbs, such as Rheum palmatum, Polygonum cuspidatum and Polygonum multiflorum. Emodin has been used as a traditional Chinese medicine for over 2000 years and is still present in various herbal preparations. Emerging evidence indicates that emodin possesses a wide spectrum of pharmacological properties, including anticancer, hepatoprotective, antiinflammatory, antioxidant and antimicrobial activities. However, emodin could also lead to hepatotoxicity, kidney toxicity and reproductive toxicity, particularly in high doses and with long-term use. Pharmacokinetic studies have demonstrated that emodin has poor oral bioavailability in rats because of its extensive glucuronidation. This review aims to comprehensively summarize the pharmacology, toxicity and pharmacokinetics of emodin reported to date with an emphasis on its biological properties and mechanisms of action. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27188217 TI - Industry self-regulation of alcohol marketing: a systematic review of content and exposure research. AB - BACKGROUND AND AIMS: With governments relying increasingly upon the alcohol industry's self-regulated marketing codes to restrict alcohol marketing activity, there is a need to summarize the findings of research relevant to alcohol marketing controls. This paper provides a systematic review of studies investigating the content of, and exposure to, alcohol marketing in relation to self-regulated guidelines. METHODS: Peer-reviewed papers were identified through four literature search engines: SCOPUS, Web of Science, PubMed and PsychINFO. Non peer-reviewed reports produced by public health agencies, alcohol research centers, non-governmental organizations and government research centers were also identified. Ninety-six publications met the inclusion criteria. RESULTS: Of the 19 studies evaluating a specific marketing code and 25 content analysis studies reviewed, all detected content that could be considered potentially harmful to children and adolescents, including themes that appeal strongly to young men. Of the 57 studies of alcohol advertising exposure, high levels of youth exposure and high awareness of alcohol advertising were found for television, radio, print, digital and outdoor advertisements. Youth exposure to alcohol advertising has increased over time, even as greater compliance with exposure thresholds has been documented. CONCLUSIONS: Violations of the content guidelines within self regulated alcohol marketing codes are highly prevalent in certain media. Exposure to alcohol marketing, particularly among youth, is also prevalent. Taken together, the findings suggest that the current self-regulatory systems that govern alcohol marketing practices are not meeting their intended goal of protecting vulnerable populations. PMID- 27188219 TI - Tell it to a child! A brain stimulation study of the role of left inferior frontal gyrus in emotion regulation during storytelling. AB - In everyday life we need to continuously regulate our emotional responses according to their social context. Strategies of emotion regulation allow individuals to control time, intensity, nature and expression of emotional responses to environmental stimuli. The left inferior frontal gyrus (LIFG) is involved in the cognitive control of the selection of semantic content. We hypothesized that it might also be involved in the regulation of emotional feelings and expressions. We applied continuous theta burst stimulation (cTBS) over LIFG or a control site before a newly-developed ecological regulation task that required participants to produce storytelling of pictures with negative or neutral valence to either a peer (unregulated condition) or a child (regulated condition). Linguistic, expressive, and physiological responses were analyzed in order to assess the effects of LIFG-cTBS on emotion regulation. Results showed that the emotion regulation context modulated the emotional content of narrative productions, but not the physiologic orienting response or the early expressive behavior to negative stimuli. Furthermore, LIFG-cTBS disrupted the text-level structuring of negative picture storytelling and the early cardiac and muscular response to negative pictures; however, it did not affect the contextual emotional regulation of storytelling. These results may suggest that LIFG is involved in the initial detection of the affective arousal of emotional stimuli. PMID- 27188218 TI - Electric fields of motor and frontal tDCS in a standard brain space: A computer simulation study. AB - The electric field produced in the brain is the main physical agent of transcranial direct current stimulation (tDCS). Inter-subject variations in the electric fields may help to explain the variability in the effects of tDCS. Here, we use multiple-subject analysis to study the strength and variability of the group-level electric fields in the standard brain space. Personalized anatomically-accurate models of 62 subjects were constructed from T1- and T2 weighted MRI. The finite-element method was used to computationally estimate the individual electric fields, which were registered to the standard space using surface based registration. Motor cortical and frontal tDCS were modelled for 16 electrode montages. For each electrode montage, the group-level electric fields had a consistent strength and direction in several brain regions, which could also be located at some distance from the electrodes. In other regions, the electric fields were more variable, and thus more likely to produce variable effects in each individual. Both the anode and cathode locations affected the group-level electric fields, both directly under the electrodes and elsewhere. For motor cortical tDCS, the electric fields could be controlled at the group level by moving the electrodes. However, for frontal tDCS, the group-level electric fields were more variable, and the electrode locations had only minor effects on the group average fields. Our results reveal the electric fields and their variability at the group level in the standard brain space, providing insights into the mechanisms of tDCS for plasticity induction. The data are useful for planning, analysing and interpreting tDCS studies. PMID- 27188220 TI - Integrin CD11b attenuates colitis by strengthening Src-Akt pathway to polarize anti-inflammatory IL-10 expression. AB - Interleukin-10 (IL-10) plays a central role in regulation of intestinal mucosal homeostasis and prevention of inflammatory bowel disease (IBD). We previously reported that CD11b(hi) regulatory dendritic cells (DCs) can produce more IL-10, and CD11b can negatively regulate Toll-like receptors (TLRs)-induced inflammatory responses in macrophages. However whether CD11b and its signaling can control autoimmunity via IL-10 production remains unclear. Here we found that CD11b deficient (Itgam(-/-)) mice were more susceptible to dextran sulfate sodium (DSS) induced colitis, with more tumor necrosis factor alpha (TNF-alpha) while less IL 10 production. CD11b inhibited nuclear factor-kappa B (NF-kappaB) while promoted activator protein 1 (AP-1) activation through activating sarcoma oncogene (Src), leading to decreased TNF-alpha while increased IL-10 production. Src interacted with and promoted c-casitas B lineage lymphoma proto-oncogene (c-Cbl)-mediated degradation of the inhibitory subunit p85 of phosphatidylinositol 3-kinase (PI3K). Importantly, Src inhibitor dasatinib aggravated DSS-induced colitis by decreasing IL-10 while increasing TNF-alpha in vivo. Therefore, CD11b promotes IL 10 production by activating Src-Akt signal pathway. An axis of CD11b-Src pathway is important in balancing homeostasis of TLR-induced pro-inflammatory and anti inflammatory responses. PMID- 27188221 TI - Blunted Cortisol Awakening Response and Poor Self-Perceived Health in Informal Caregivers of People with Eating Disorders. AB - Caring for offspring diagnosed with eating disorders (EDs) entails being under high chronic stress, with negative consequences for health. However, most previous research has only evaluated self-report measures of health, biological markers being poorly studied. In this regard, the evaluation of the cortisol awakening response (CAR) could add significant information about the biological basis of health disturbances in this population. The main aim of the present study was to compare CAR and self-reported health between informal caregivers (ICs) of people with EDs and non-caregivers. Furthermore, we explored the effect of the nature of the diagnosis, comparing ICs of people with anorexia and bulimia nervosa. ICs had a blunted CAR, and more anxiety and insomnia, and social dysfunction, together with poorer perceived general health than non-caregivers. ICs of people with anorexia nervosa had higher levels of morning cortisol and burden, and more social dysfunction and severe depression than those of people with bulimia nervosa. Our results demonstrate marked health problems in ICs of people with EDs, especially when the care recipient has anorexia nervosa. Copyright (c) 2016 John Wiley & Sons, Ltd and Eating Disorders Association. PMID- 27188222 TI - Measuring the course of anxiety in women giving birth by caesarean section: a prospective study. AB - BACKGROUND: Women undergoing elective caesarean section experience anxiety. However, course, extent and duration of anxiety have not been investigated yet. This study aimed to explore anxiety levels during the course of the day of surgery by employing and comparing subjective as well as objective measures. By examining their correlation it is intended to give methodological support for interventional studies. METHODS: This is a monocentric, prospectively planned study in which 47 women with an indication for primary caesarean section took part. Anxiety levels were evaluated using the State-Trait Anxiety Inventory (STAI trait and STAI-state), the visual analogue scale for anxiety (VASA) as well as saliva cortisol at three time points on the day of the caesarean section (at admission, at skin closure and 2 h post surgery). RESULTS: Peak anxiety levels for the STAI-state and VASA were highest at admission and showed significant decreases to skin closure (p < .001). The subjective measures correlated significantly at all time points (p-values < .001). For cortisol levels the peak level of anxiety was shown at skin closure with a significant increase from admission to skin closure and a significant decrease from skin closure to 2 h post operation (p-values < .001). Additionally women with STAI-trait scores above the median showed significantly higher levels at the peaks of anxiety. CONCLUSION: The study reveals the course of anxiety on the day of the caesarean section. A strong correlation of STAI-state and VASA was demonstrated. Cortisol showed a different course, which fits into its known biological kinetics. Taking into account all measures, anxiety seems to be most bothersome before surgery until skin closure. In a differentiated approach using STAI-trait scores as a discriminator we showed that the group with STAI-trait levels above the median is particularly prone to develop anxiety in the setting of the caesarean section and might therefore mostly be in need of an intervention against anxiety. PMID- 27188224 TI - [Bordetella petrii chronic colonization. First case in Spain]. PMID- 27188225 TI - [Successful treatment of Abiotrophia defective endophthalmitis]. PMID- 27188223 TI - Melanoma. AB - Melanoma is a common cancer in the Western world with an increasing incidence. Sun exposure is still considered to be the major risk factor for melanoma. The prognosis of patients with malignant (advanced-stage) melanoma differs widely between countries, but public campaigns advocating early detection have led to significant reductions in mortality rates. As well as sun exposure, distinct genetic alterations have been identified as associated with melanoma. For example, families with melanoma who have germline mutations in CDKN2A are well known, whereas the vast majority of sporadic melanomas have mutations in the mitogen-activated protein kinase cascade, which is the pathway with the highest oncogenic and therapeutic relevance for this disease. BRAF and NRAS mutations are typically found in cutaneous melanomas, whereas KIT mutations are predominantly observed in mucosal and acral melanomas. GNAQ and GNA11 mutations prevail in uveal melanomas. Additionally, the PI3K-AKT-PTEN pathway and the immune checkpoint pathways are important. The finding that programmed cell death protein 1 ligand 1 (PDL1) and PDL2 are expressed by melanoma cells, T cells, B cells and natural killer cells led to the recent development of programmed cell death protein 1 (PD1)-specific antibodies (for example, nivolumab and pembrolizumab). Alongside other new drugs - namely, BRAF inhibitors (vemurafenib and dabrafenib) and MEK inhibitors (trametinib and cobimetinib) - these agents are very promising and have been shown to significantly improve prognosis for patients with advanced stage metastatic disease. Early signs are apparent that these new treatment modalities are also improving long-term clinical benefit and the quality of life of patients. This Primer summarizes the current understanding of melanoma, from mechanistic insights to clinical progress. For an illustrated summary of this Primer, visit: http://go.nature.com/vX2N9s. PMID- 27188226 TI - Vitamin D levels in allergic rhinitis: a systematic review and meta-analysis. AB - BACKGROUND: We aimed to systematically review observational studies investigating the relationship between vitamin D levels and allergic rhinitis (AR). METHODS: Studies were selected if they evaluated the relationship between vitamin D levels and AR, and included studies that evaluated other allergic conditions if those studies also contained data on AR. We assessed the incidence and prevalence of AR according to vitamin D levels and compared vitamin D levels in patients with AR to levels in controls. RESULTS: Nineteen studies were selected. Of these, only seven focused solely on AR; 10 studies evaluated the other allergic diseases as well as AR; and two studies evaluated asthma primarily, but also included data on patients with AR. The pooled odds ratios (ORs) for the incidence of AR according to vitamin D levels were not statistically significant for either children or adults. Lower vitamin D levels were associated with a higher AR prevalence only in children (pooled OR [95% confidence interval (CI)], 0.75 [0.58, 0.98]). The pooled mean vitamin D level in patients with AR was lower than that of controls only in children (pooled means difference [95% CI], -7.63 [-13.08, -2.18]). CONCLUSIONS: Prior vitamin D levels were not related to developing AR, but lower vitamin D levels were associated with a higher AR prevalence only in children. There is insufficient evidence to support vitamin D supplementation for AR prevention. However, physicians should consider evaluating patients for vitamin D deficiency during AR management, especially in children. PMID- 27188227 TI - Reasons doctors provide futile treatment at the end of life: a qualitative study. AB - OBJECTIVE: Futile treatment, which by definition cannot benefit a patient, is undesirable. This research investigated why doctors believe that treatment that they consider to be futile is sometimes provided at the end of a patient's life. DESIGN: Semistructured in-depth interviews. SETTING: Three large tertiary public hospitals in Brisbane, Australia. PARTICIPANTS: 96 doctors from emergency, intensive care, palliative care, oncology, renal medicine, internal medicine, respiratory medicine, surgery, cardiology, geriatric medicine and medical administration departments. Participants were recruited using purposive maximum variation sampling. RESULTS: Doctors attributed the provision of futile treatment to a wide range of inter-related factors. One was the characteristics of treating doctors, including their orientation towards curative treatment, discomfort or inexperience with death and dying, concerns about legal risk and poor communication skills. Second, the attributes of the patient and family, including their requests or demands for further treatment, prognostic uncertainty and lack of information about patient wishes. Third, there were hospital factors including a high degree of specialisation, the availability of routine tests and interventions, and organisational barriers to diverting a patient from a curative to a palliative pathway. Doctors nominated family or patient request and doctors being locked into a curative role as the main reasons for futile care. CONCLUSIONS: Doctors believe that a range of factors contribute to the provision of futile treatment. A combination of strategies is necessary to reduce futile treatment, including better training for doctors who treat patients at the end of life, educating the community about the limits of medicine and the need to plan for death and dying, and structural reform at the hospital level. PMID- 27188228 TI - The mitochondrial genome of the egg-laying flatworm Aglaiogyrodactylus forficulatus (Platyhelminthes: Monogenoidea). AB - BACKGROUND: The rather species-poor oviparous gyrodactylids are restricted to South America. It was suggested that they have a basal position within the otherwise viviparous Gyrodactylidae. Accordingly, it was proposed that the species-rich viviparous gyrodactylids diversified and dispersed from there. METHODS: The mitochondrial genome of Aglaiogyrodactylus forficulatus was bioinformatically assembled from next-generation illumina MiSeq sequencing reads, annotated, and compared to previously published mitochondrial genomes of other monogenoidean flatworm species. RESULTS: The mitochondrial genome of A. forficulatus consists of 14,371 bp with an average A + T content of 75.12 %. All expected 12 protein coding, 22 tRNA, and 2 rRNA genes were identified. Furthermore, there were two repetitive non-coding regions essentially consisting of 88 bp and 233 bp repeats, respectively. Maximum Likelihood analyses placed the mitochondrial genome of A. forficulatus in a well-supported clade together with the viviparous Gyrodactylidae species. The gene order differs in comparison to that of other monogenoidean species, with rearrangements mainly affecting tRNA genes. In comparison to Paragyrodactylus variegatus, four gene order rearrangements, i.e. three transpositions and one complex tandem-duplication random-loss event, were detected. CONCLUSION: Mitochondrial genome sequence analyses support a basal position of the oviparous A. forficulatus within Gyrodactylidae, and a sister group relationship of the oviparous and viviparous forms. PMID- 27188229 TI - Improving fertility preservation for girls and women by coupling oocyte in vitro maturation with existing strategies. PMID- 27188230 TI - Ruthenium and ruthenium oxide nanofiber supports for enhanced activity of platinum electrocatalysts in the methanol oxidation reaction. AB - Novel supports for the dispersion of Pt electrocatalysts in fuel cells are constantly being developed in order to improve the electrochemical performance and reduce the cost. The electrocatalytic activity and stability in fuel cells largely depend on the surface morphology and structure of the support. In this study, Ru and RuO2 nanofibers prepared by electrospinning and post-calcination have been considered as Pt-catalyst supports. The composite material loaded with 20 wt% Pt catalyst exhibited a high anodic current density of 641.7 mA mgPt(-1), a high IF/IB ratio of 1.9, and excellent electrocatalytic stability compared to commercial Pt/C. The improved anodic current density of the composite is attributed to the high dispersion of the Pt catalyst over the large surface area of the nanosized support grains, while its low onset potential, high IF/IB ratio, and excellent electrocatalytic stability are ascribed to a bifunctional effect resulting from the existence of Ru atoms on the support surface. Finally, the efficient electron transfer and a rapid diffusion rate of the electrolyte are due to the unique network structure of the supports. Thus, the Ru and RuO2 nanofiber composites act as promising Pt-catalyst supports for the methanol oxidation reaction. PMID- 27188232 TI - Splenic scintigraphy for further differentiation of unclear (68) Ga-DOTATOC PET/CT findings: Strengths and limitations. AB - Splenic scintigraphy has been described to be a powerful tool in unclear (68 ) Ga DOTATOC-PET/CT findings, allowing differentiation between somatostatin receptor (Sst)-positive tissue deriving from neuroendocrine tumour (NET) and functioning splenic tissue. However, our own experiences sometimes show a lack of identification on splenic scintigraphy, especially in small lesions, leading to uncertainties regarding the safe identification of NET or splenic tissue. Here, we report on 10 cases with (68) Ga-DOTATOC-PET/CT and (99m) Tc-heat-denaturated red blood cell (HDRBC) scintigraphy and we illustrate the strengths and limitations of (99m) Tc-HDRBC scintigraphy in this context. PMID- 27188231 TI - Morc3 mutant mice exhibit reduced cortical area and thickness, accompanied by altered haematopoietic stem cells niche and bone cell differentiation. AB - Morc3, a member of a highly conserved nuclear matrix protein super-family plays an important part in chromatin remodeling, DNA repair, epigenetic regulation and cellular senescence. However, its role in bone homeostasis is not known. In the present study, a phenotype-driven ENU mouse mutagenesis screen revealed that Morc3(mut +/-) mice exhibit reduced cortical area and thickness with increased cortical porosity. Morc3(mut +/-) mice displayed reduced osteoclast numbers and surface per bone surface as well as osteocyte numbers, concomitant with altered gene expressions such as Rankl/Opg and Sost in ex vivo long bones. In vitro experiments revealed a significant increase in the number of Sca-1(+)/c-kit(+) haematopoietic stem cells (HSCs), and a significant reduction in senescence associated beta-galactosidase activity in bone marrow macrophages (BMMs). In addition, we observed a decrease in osteoclastogenesis and bone resorption accompanied by upregulation of STAT1 expression in osteoclast lineage cells. Strikingly, Morc3 protein localization within the nuclear membrane was shifted to the cytoplasm in Morc3(mut +/-) osteoclasts. Further, Morc3(mut +/-) mice displayed increased osteoblast differentiation and altered gene expression. Collectively, our data show that Morc3 is a previously unreported regulator of cortical bone homeostasis and haematopoietic stem cells niche, accompanied by altered bone cell differentiation. PMID- 27188234 TI - Comparison study of clinical outcomes between single-site robotic cholecystectomy and single incision laparoscopic cholecystectomy. AB - BACKGROUND: Multiport laparoscopic cholecystectomy is the standard surgical procedure for symptomatic gallbladder diseases. The latest evolution is single incision laparoscopic cholecystectomy (SILC). Single-site robotic cholecystectomy (SSRC) overcomes several limitations of manual SILC. The aim of this study is to present our initial experiences in SSRC and to compare its clinical outcomes with those of SILC. METHODS: This study retrospectively reviewed data for patients who received SSRC or SILC from February 2014 to September 2015. The following variables were analyzed: age, sex, body mass index, indications, pain scale, length of stay, and complications. The data were analyzed with Student t test or by Fisher exact test. RESULTS: The analysis included 51 SSRC (33 women, 18 men) and 63 SILC patients (40 women, 23 men). Patients in both groups had similar demographic features and indications for surgery. The SSRC group required no conversions to conventional laparoscopy and no additional trocars, whereas the SILC group had two (3.17%) cases. Length of stay did not significantly differ between the SSRC and SILC groups (4.29 +/- 0.72 vs. 4.13 +/- 0.93 days, respectively; p = 0.823). However, the SSRC group had shorter operative time (71.30 +/- 48.88 vs. 74.70 +/- 30.16 minutes; p = 0.772), less perioperative bile spillage (9.81% vs. 19.05%; p = 0.189), and less postoperative bile leakage (0% vs. 3.17%; p = 0.501). However, the parameters mentioned above were not statistically significant, whereas pain scale scores were significantly lower in the SSRC group (2.11 +/- 0.76 vs. 3.98 +/- 0.84; p < 0.01). CONCLUSIONS: Both SSRC and SILC are safe and feasible procedures for performing single incision cholecystectomy. SSRC, however, has the advantage of significantly decreased postoperative pain. PMID- 27188233 TI - Patients with first-episode, drug-naive schizophrenia and subjects at ultra-high risk of psychosis shared increased cerebellar-default mode network connectivity at rest. AB - Increased cerebellar-default mode network (DMN) connectivity has been observed in first-episode, drug-naive patients with schizophrenia. However, it remains unclear whether increased cerebellar-DMN connectivity starts earlier than disease onset. Thirty-four ultra-high risk (UHR) subjects, 31 first-episode, drug-naive patients with schizophrenia and 37 healthy controls were enrolled for a resting state scan. The imaging data were analyzed using the seed-based functional connectivity (FC) method. Compared with the controls, UHR subjects and patients with schizophrenia shared increased connectivity between the right Crus I and bilateral posterior cingulate cortex/precuneus and between Lobule IX and the left superior medial prefrontal cortex. There are positive correlations between the right Crus I-bilateral precuneus connectivity and clinical variables (Structured Interview for Prodromal Syndromes/Positive and Negative Symptom Scale negative symptoms/total scores) in the UHR subjects. Increased cerebellar-DMN connectivity shared by the UHR subjects and the patients not only highlights the importance of the DMN in the pathophysiology of psychosis but also may be a trait alteration for psychosis. PMID- 27188235 TI - Prevalence of sacrococcygeal pilonidal disease in Turkey. AB - BACKGROUND: Pilonidal sinus disease is frequently observed in the producing population; despite it not being a malignant disease, attention of clinicians to this disease has increased. Studies on this disease have not clearly revealed its prevalence. We aimed to detect its dispersion characteristics in our country. MATERIALS AND METHODS: Our study was designed as a descriptive study involving a large number of patients. A total of 19,013 candidates, aged between 17 years and 28 years and coming from different regions of the country, who applied to be students or officials of the state's schools and institutions, were enrolled in the study. Examination was performed including the perineal region, the presence of any comorbid diseases was noted, and clinical types of pilonidal sinus disease were detected according to Tezel's classification and recorded. RESULTS: Pilonidal sinus was detected in a total of 1258 (6.6%) candidates, of whom 72 (0.37%) were female and 1186 (6.23%) male. Our clinical experience showed that pilonidal cysts had a higher incidence in the Turkish population than in other populations, and it was especially increased in individuals of military age. CONCLUSION: We believe that soldiers coming from different regions of Turkey and candidates applying for auxiliary staff positions provide a small sample group resembling a representation of the whole of Turkey. PMID- 27188236 TI - Moroxydine hydrochloride inhibits grass carp reovirus replication and suppresses apoptosis in Ctenopharyngodon idella kidney cells. AB - Moroxydine hydrochloride (Mor) is known to have multi-antiviral activities against DNA and RNA viruses but very little information exists on its pharmacology. The paper was undertaken to explore the antiviral response and antiapoptotic mechanism of Mor against grass carp reovirus (GCRV) in Ctenopharyngodon idella kidney (CIK) cells. The results showed that exposing GCRV infected cell to 6.3 MUg mL(-1) of Mor for 96 h avoid ca. 50% apoptosis. Meanwhile, Mor had lower cytotoxicity than ribavirin (Rib) as the value of safe concentration was threefold higher than effective concentration and the compound could ensure sufficient into and out of cells within 4 h when tested at the maximal safe concentration. Mor blocked the GCRV-induced cytopathic effects and eliminated nucleocapsids in CIK cells to keep the normal morphological structure. Moreover, the expressions of viral protein genes were significantly inhibited especially the guanylyl transferase and RNA-dependent RNA polymerase related expression. Furthermore, GCRV caused Bcl-2 down-regulation and Bax mitochondrial translocation was prevented by treatment of CIK cells with Mor. The downstream effector, caspase activity was also significantly inhibited in Mor treated cells. The potential mechanism might be that mitochondrial apoptotic signals were not activated by the intervention of Mor for targeting viral gene expression. Taken together, Mor showed high anti-GCRV activity and had been proved as a secure and promising agent in viral controlling in aquaculture industry. PMID- 27188238 TI - Taking a stand against predatory publishers. PMID- 27188237 TI - Contrasting Linguistic and Genetic Origins of the Asian Source Populations of Malagasy. AB - The Austronesian expansion, one of the last major human migrations, influenced regions as distant as tropical Asia, Remote Oceania and Madagascar, off the east coast of Africa. The identity of the Asian groups that settled Madagascar is particularly mysterious. While language connects Madagascar to the Ma'anyan of southern Borneo, haploid genetic data are more ambiguous. Here, we screened genome-wide diversity in 211 individuals from the Ma'anyan and surrounding groups in southern Borneo. Surprisingly, the Ma'anyan are characterized by a distinct, high frequency genomic component that is not found in Malagasy. This novel genetic layer occurs at low levels across Island Southeast Asia and hints at a more complex model for the Austronesian expansion in this region. In contrast, Malagasy show genomic links to a range of Island Southeast Asian groups, particularly from southern Borneo, but do not have a clear genetic connection with the Ma'anyan despite the obvious linguistic association. PMID- 27188240 TI - Associations between hospital-wide readmission rates and mortality measures at the hospital level: Are hospital-wide readmissions a measure of quality? PMID- 27188239 TI - An intein-mediated modulation of protein stability system and its application to study human cytomegalovirus essential gene function. AB - Functional analysis of the essential proteins encoded by human cytomegalovirus (HCMV) is hindered by the lack of complementing systems. To overcome this difficulty, we have established a novel approach, termed the intein-mediated modulation of protein stability (imPS), in which a destabilizing domain and part of a split intein are fused to the essential protein. The growth of the mutant virus can then be regulated by the degradation and splicing of the protein. We found that an ultrafast gp41-1 split intein was able to rescue or degrade the protein of interest (POI) by removing or adding a strong degron through protein splicing. As a result, the function of the POI was turned on or off during the process. Using HCMV essential gene IE1/IE2, we confirmed that imPS worked remarkably well in conditionally regulating protein stability during viral infection. This conditional approach is likely to be applicable for dissecting the gene functions of HCMV or other viruses. PMID- 27188242 TI - Novel piroxicam-loaded nanospheres generated by the electrospraying technique: physicochemical characterisation and oral bioavailability evaluation. AB - To determine if a novel electrospraying technique could be applied to an oral drug delivery system for improving the solubility and oral bioavailability of poorly water-soluble piroxicam; the nanospheres were generated with drug and polyvinylpyrrolidone (PVP) using electrospraying technique; and their physicochemical properties, solubility, release and pharmacokinetics were evaluated in comparison with piroxicam powder. All nanospheres had significantly increased drug solubility and dissolution rates in comparison with the drug powder. In particular, the nanosphere composed of piroxicam and PVP at a weight ratio of 2:8 gave about 600-fold higher solubility, 15-fold higher release rate and 3-fold higher AUC in comparison to piroxicam powder, leading to significantly enhanced oral bioavailability in rats, due to the mingled effect of nanonisation along with transformation to the amorphous state. Thus, this electrospraying technique can be utilised to produce a novel oral nanosphere delivery system with enhanced solubility and oral bioavailability for poorly water-soluble piroxicam. PMID- 27188241 TI - Early neurological deterioration after thrombolysis: Clinical and imaging predictors. AB - BACKGROUND: National Institutes of Health Stroke Scale is the most common scale used in stroke patients. An increase of four points or more within 24 h signifies early neurological deterioration. We aimed to establish how often early neurological deterioration occurs in a cohort selected by magnetic resonance imaging and which factors predicted early neurological deterioration. METHODS: In this single-center study, we collected epidemiological, imaging and outcome data on 569 consecutive patients undergoing reperfusion therapy after magnetic resonance imaging selection. RESULTS: Of these, 33 (5.8%) experienced early neurological deterioration. Seven were due to a symptomatic intracerebral hemorrhage, 23 were caused by extension of ischemia on follow-up imaging and three were due to progression on the basis of small vessel disease. Early neurological deterioration was predicted by a larger perfusion lesion, higher blood glucose and presence of large vessel disease. Penumbra occurred in 34% of patients but only 9% of patients with penumbra experienced early neurological deterioration, thus eroding the value of penumbra as an imaging marker. Early neurological deterioration was a poor prognostic sign. Odds ratio for disability or death was 14.9 (95% confidence interval: 6.5-34.0). CONCLUSION: Early neurological deterioration is rare. It originates mainly from ischemic infarct growth rather than from hemorrhage. Concern should be highest in patients with elevated blood glucose, larger perfusion lesions and large vessel disease. Prior aspirin use increases risk of symptomatic intracerebral hemorrhage. PMID- 27188243 TI - Fe-Catalyzed Hydroalkylation of Olefins with para-Quinone Methides. AB - A novel Fe-catalyzed hydroalkylation of olefins with para-quinone methides (p QMs) for accessing phenols has been developed. In this protocol, various olefins could convert to alkyl radicals and undergo addition to para-quinone methides toward C-C bond formation and aromatization. The reaction conditions are mild and the substrate scopes are broad. PMID- 27188245 TI - Is treatment de-escalation a reality in HPV related oropharyngeal cancer? AB - The incidence of HPV related oropharyngeal squamous cell carcinoma (OPSCC) is rapidly increasing. It is now well recognised as a distinct clinical and biologic entity, compared to traditional OPSCC. The majority of these patients have an excellent prognosis due to the chemo-radiosensitive nature of these tumours. The de-escalation of current treatment regimens have therefore been proposed in an attempt to reduce the long term treatment related morbidity of this much younger patient cohort. Several of the more pertinent points regarding safe de-escalation strategies are considered within this manuscript. PMID- 27188246 TI - Using Insights From Behavioral Economics to Strengthen Disaster Preparedness and Response. AB - Behavioral economics is based on the idea that individuals' decisions are affected by systematic and predictable cognitive biases and that these same biases can be leveraged to change behavior and improve decision-making. Insights from behavioral economics have been used to encourage a range of desired behaviors but have rarely been used in disaster preparedness and response, though traditional efforts by public health practitioners have failed to increase adoption of key preparedness behaviors. In this work, we aim to show how some of the key concepts in the behavioral economics literature are applicable to behaviors related to disaster preparedness and response, and we present ideas for behavioral economics-based interventions that we vetted with public health officials. Two of the best-received interventions were applications of social norms approaches, which leverage social influence bias, and commitment devices, which leverage present bias and loss aversion. Although the current evidence base for the applications of concepts from behavioral economics in disaster preparedness and response is weak, behavioral economics has achieved positive results in similar decision-making contexts. The low cost and potentially high impact of behavioral economics-based interventions warrant further investigation and testing. (Disaster Med Public Health Preparedness. 2016;page 1 of 7). PMID- 27188244 TI - Molecular composition of GAG-collagen I multilayers affects remodeling of terminal layers and osteogenic differentiation of adipose-derived stem cells. AB - The effect of molecular composition of multilayers, by pairing type I collagen (Col I) with either hyaluronic acid (HA) or chondroitin sulfate (CS) was studied regarding the osteogenic differentiation of adhering human adipose-derived stem cells (hADSCs). Polyelectrolyte multilayer (PEM) formation was based primarily on ion pairing and on additional intrinsic cross-linking through imine bond formation with Col I replacing native by oxidized HA (oHA) or CS (oCS). Significant amounts of Col I fibrils were found on both native and oxidized CS based PEMs, resulting in higher water contact angles and surface potential under physiological condition, while much less organized Col I was detected in either HA-based multilayers, which were more hydrophilic and negatively charged. An important finding was that hADSCs remodeled Col I at the terminal layers of PEMs by mechanical reorganization and pericellular proteolytic degradation, being more pronounced on CS-based PEMs. This was in accordance with the higher quantity of Col I deposition in this system, accompanied by more cell spreading, focal adhesions (FA) formation and significant alpha2beta1 integrin recruitment compared to HA-based PEMs. Both CS-based PEMs caused also an increased fibronectin (FN) secretion and cell growth. Furthermore, significant calcium phosphate deposition, enhanced ALP, Col I and Runx2 expression were observed in hADSCs on CS-based PEMs, particularly on oCS-containing one. Overall, multilayer composition can be used to direct cell-matrix interactions, and hence stem cell fates showing for the first time that PEMs made of biogenic polyelectrolytes undergo significant remodeling of terminal protein layers, which seems to enable cells to form a more adequate extracellular matrix-like environment. STATEMENT OF SIGNIFICANCE: Natural polymer derived polyelectrolyte multilayers (PEMs) have been recently applied to adjust biomaterials to meet specific tissue demands. However, the effect of molecular composition of multilayers on both surface properties and cellular response, especially the fate of human adipose derived stem cells (hADSCs) upon osteogenic differentiation has not been studied extensively, yet. In addition, no studies exist that investigate a potential cell dependent remodeling of PEMs made of extracellular matrix (ECM) components like collagens and glycosaminoglycans (GAGs). Furthermore, there is no knowledge whether the ability of cells to remodel PEM components may provide an added value regarding cell growth and differentiation. Finally, it has not been explored yet, how intrinsic cross-linking of ECM derived polyelectrolytes that improve the stability of PEMs will affect the differentiation potential of hADSCs. The current work aims to address these questions and found that the type of GAG has a strong effect on properties of multilayers and osteogenic differentiation of hADSCs. Additionally, we also show for the first time that PEMs made of biogenic polyelectrolytes undergo significant remodeling of terminal layers as completely new finding, which allows cells to form an ECM-like environment supporting differentiation upon osteogenic lineage. The finding of this work may open new avenues of application of PEM systems made by layer by layer (LbL) technique in tissue engineering and regenerative medicine. PMID- 27188247 TI - Polymer Membranes with Vertically Oriented Pores Constructed by 2D Freezing at Ambient Temperature. AB - Polymer membranes with well-controlled and vertically oriented pores are of great importance in the applications for water treatment and tissue engineering. On the basis of two-dimensional solvent freezing, we report environmentally friendly facile fabrication of such membranes from a broad spectrum of polymer resources including poly(vinylidene fluoride), poly(l-lactic acid), polyacrylonitrile, polystyrene, polysulfone and polypropylene. Dimethyl sulfone, diphenyl sulfone, and arachidic acid are selected as green solvents crystallized in the polymer matrices under two-dimensional temperature gradients induced by water at ambient temperature. Parallel Monte Carlo simulations of the lattice polymers demonstrate that the directional process is feasible for each polymer holding suitable interaction with a corresponding solvent. As a typical example of this approach, poly(vinylidene fluoride) membranes exhibit excellent tensile strength, high optical transparence, and outstanding separation performance for the mixtures of yeasts and lactobacilli. PMID- 27188249 TI - The space of ultrametric phylogenetic trees. AB - The reliability of a phylogenetic inference method from genomic sequence data is ensured by its statistical consistency. Bayesian inference methods produce a sample of phylogenetic trees from the posterior distribution given sequence data. Hence the question of statistical consistency of such methods is equivalent to the consistency of the summary of the sample. More generally, statistical consistency is ensured by the tree space used to analyse the sample. In this paper, we consider two standard parameterisations of phylogenetic time-trees used in evolutionary models: inter-coalescent interval lengths and absolute times of divergence events. For each of these parameterisations we introduce a natural metric space on ultrametric phylogenetic trees. We compare the introduced spaces with existing models of tree space and formulate several formal requirements that a metric space on phylogenetic trees must possess in order to be a satisfactory space for statistical analysis, and justify them. We show that only a few known constructions of the space of phylogenetic trees satisfy these requirements. However, our results suggest that these basic requirements are not enough to distinguish between the two metric spaces we introduce and that the choice between metric spaces requires additional properties to be considered. Particularly, that the summary tree minimising the square distance to the trees from the sample might be different for different parameterisations. This suggests that further fundamental insight is needed into the problem of statistical consistency of phylogenetic inference methods. PMID- 27188250 TI - Mathematical model of plant-virus interactions mediated by RNA interference. AB - Cross-protection, which refers to a process whereby artificially inoculating a plant with a mild strain provides protection against a more aggressive isolate of the virus, is known to be an effective tool of disease control in plants. In this paper we derive and analyse a new mathematical model of the interactions between two competing viruses with particular account for RNA interference. Our results show that co-infection of the host can either increase or decrease the potency of individual infections depending on the levels of cross-protection or cross enhancement between different viruses. Analytical and numerical bifurcation analyses are employed to investigate the stability of all steady states of the model in order to identify parameter regions where the system exhibits synergistic or antagonistic behaviour between viral strains, as well as different types of host recovery. We show that not only viral attributes but also the propagating component of RNA-interference in plants can play an important role in determining the dynamics. PMID- 27188248 TI - Developing a Cognition Endpoint for Traumatic Brain Injury Clinical Trials. AB - Cognitive impairment is a core clinical feature of traumatic brain injury (TBI). After TBI, cognition is a key determinant of post-injury productivity, outcome, and quality of life. As a final common pathway of diverse molecular and microstructural TBI mechanisms, cognition is an ideal endpoint in clinical trials involving many candidate drugs and nonpharmacological interventions. Cognition can be reliably measured with performance-based neuropsychological tests that have greater granularity than crude rating scales, such as the Glasgow Outcome Scale-Extended, which remain the standard for clinical trials. Remarkably, however, there is no well-defined, widely accepted, and validated cognition endpoint for TBI clinical trials. A single cognition endpoint that has excellent measurement precision across a wide functional range and is sensitive to the detection of small improvements (and declines) in cognitive functioning would enhance the power and precision of TBI clinical trials and accelerate drug development research. We outline methodologies for deriving a cognition composite score and a research program for validation. Finally, we discuss regulatory issues and the limitations of a cognition endpoint. PMID- 27188251 TI - Theoretical knock-outs on biological networks. AB - In this work we redefine the concept of biological importance and how to compute it, based on a model of complex networks and random walk. We call this new procedure, theoretical knock-out (KO). The proposed method generalizes the procedure presented in a recent study about Oral Tolerance. To devise this method, we make two approaches: algebraically and algorithmically. In both cases we compute a vector on an asymptotic state, called flux vector. The flux is given by a random walk on a directed graph that represents a biological phenomenon. This vector gives us the information about the relative flux of walkers on a vertex which represents a biological agent. With two vector of this kind, we can calculate the relative mean error between them by averaging over its coefficients. This quantity allows us to assess the degree of importance of each vertex of a complex network that evolves in time and has experimental background. We find out that this procedure can be applied in any sort of biological phenomena in which we can know the role and interrelationships of its agents. These results also provide experimental biologists to predict the order of importance of biological agents on a mounted complex network. PMID- 27188252 TI - Stability and convergence analysis of a variable order replicator-mutator process in a moving medium. AB - A more generalized approach, the concept of variable order derivative, is used to study the well-known replicator-mutator dynamics taking place in a moving medium. The biological relevance of the variable order context is explored via the language learning in social groups and stability of fixed points for the generalized model is recalled and discussed. Related graphs are plotted for different values of the derivative order gamma. It happens that the threshold condition for learning accuracy symbolized by a function of payoff is a monotonically increasing function irrespective of the value of the time derivative order. Also, the limit cycles and their amplitudes are shown to vary with the value of the derivative order gamma. These amplitudes become bigger as gamma grows but the stability of the system is not affected. The generalized model, namely the variable order replicator-mutator dynamics in a moving medium is numerically solved via Crank-Nicholson scheme whose stability and convergence results are provided in details. An application to a variable order replicator mutator dynamics of a population with three strategies is presented and numerical simulations are performed for some fixed values of the position variable r and the grid points. They display limit cycles appearing and disappearing in function of the values of the position r. The amplitudes of limit cycles are also proved to proportionally depend on r and the stability of the system remains unaffected. This shows the impressive effect of the transport process on the bifurcation dynamics of the model. PMID- 27188253 TI - Progress in stem cell-based therapy for liver disease. AB - Liver transplantation has been accepted as a useful therapeutic approach for patients with end-stage liver disease. However, the mismatch between the great demand for liver transplants and the number of available donor organs underscores the urgent need for alternative therapeutic strategies for patients with acute and chronic liver failure. The rapidly growing knowledge on stem cell biology has opened new avenues toward stem cell-based therapy for liver disease. As stem cells have capacity for high proliferation and multipotent differentiation, the characteristics of stem cells fit the cell therapy. Several types of cells have been investigated as possible sources of liver regeneration: mesenchymal stem cells, hematopoietic stem cells, liver progenitor cells, induced pluripotent stem cells, and bone marrow mononuclear cells. In vitro and in vivo experiments revealed that these cells have great potential as candidates of stem cell therapy. We reviewed the reports on clinical trials of cell therapy for liver disease that have been recently undertaken using mesenchymal stem cells, hematopoietic stem cells, bone marrow mononuclear cells, and liver progenitor cells. These reports have heterogeneity of description of trial design, types of infused cells, patient population, and efficacy of therapies. We addressed these reports from these viewpoints and clarified their significance. We hope that this review article will provide a perspective on the available approaches based on stem cell-based therapy for liver disease. PMID- 27188254 TI - Genesis of the vertebrate FoxP subfamily member genes occurred during two ancestral whole genome duplication events. AB - The vertebrate FoxP subfamily genes play important roles in the construction of essential functional modules involved in physiological and developmental processes. To explore the adaptive evolution of functional modules associated with the FoxP subfamily member genes, it is necessary to study the gene duplication process. We detected four member genes of the FoxP subfamily in sea lampreys (a representative species of jawless vertebrates) through genome screenings and phylogenetic analyses. Reliable paralogons (i.e. paralogous chromosome segments) have rarely been detected in scaffolds of FoxP subfamily member genes in sea lampreys due to the considerable existence of HTH_Tnp_Tc3_2 transposases. However, these transposases did not alter gene numbers of the FoxP subfamily in sea lampreys. The coincidence between the "1-4" gene duplication pattern of FoxP subfamily genes from invertebrates to vertebrates and two rounds of ancestral whole genome duplication (1R- and 2R-WGD) events reveal that the FoxP subfamily of vertebrates was quadruplicated in the 1R- and 2R-WGD events. Furthermore, we deduced that a synchronous gene duplication process occurred for the FoxP subfamily and for three linked gene families/subfamilies (i.e. MIT family, mGluR group III and PLXNA subfamily) in the 1R- and 2R-WGD events using phylogenetic analyses and mirror-dendrogram methods (i.e. algorithms to test protein-protein interactions). Specifically, the ancestor of FoxP1 and FoxP3 and the ancestor of FoxP2 and FoxP4 were generated in 1R-WGD event. In the subsequent 2R-WGD event, these two ancestral genes were changed into FoxP1, FoxP2, FoxP3 and FoxP4. The elucidation of these gene duplication processes shed light on the phylogenetic relationships between functional modules of the FoxP subfamily member genes. PMID- 27188256 TI - Downregulation of cell division cycle 25 homolog C reduces the radiosensitivity and proliferation activity of esophageal squamous cell carcinoma. AB - Radiation therapy is one of the most important methods of contemporary cancer treatment. Cells in the G2 and M phases are more sensitive to radiation therapy, and cell division cycle 25 homolog C (CDC25C) is essential in shifting the cell cycle between these two phases. In this study, the knockdown of CDC25C in human esophageal squamous carcinoma EC9706 cells was mediated by transfecting shRNA against human CDC25C-subcloning into pGV248. The levels of CDC25C mRNA and protein expression were assessed by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting, respectively. Moreover, cell proliferation and radiosensitivity were measured. Stable CDC25C-knockdown EC9706 cell lines were successfully established. Furthermore, the proliferation of both control and CDC25C-shRNA-EC9706 cells was inhibited after the cells were treated with increasing X-ray doses, and the proliferation of the control cells was affected more significantly (p<0.05). Moreover, cell colony formation assays allowed us to reach the same conclusion. Taken together, our experiments demonstrated that the knockdown of CDC25C can reduce both the radiotherapy sensitivity and the proliferation activity of EC9706 cells. Thus, CDC25C might be a potential biomarker for radiotherapy treatment. PMID- 27188255 TI - Identification and expression of a novel carbonic anhydrase isozyme in the pufferfish Takifugu vermicularis. AB - Carbonic anhydrase (CA) is a key element for maintaining acid base balance in fish. In our present experiment, novel CA isozymes were identified from the pear puffer (Takifugu vermicularis). Based on the high homology of two predicted CA sequences of the tiger puffer (Takifugu rubripes), a 1715bp novel cDNA was obtained from T. vermicularis. The open reading frame showed a complete coding sequence of 552bp with a deduced peptide sequence of 183 amino acids that exhibited highest (97%) identity with pufferfish putative CA III and CA IV-like sequences. In addition, this translated protein sequence showed 36-37% identity with zebrafish CA IV-like, CA XVa, CA XVb, and CA XVc proteins. Phylogenetic analysis revealed that the pufferfish novel protein (pCAn) was a membrane-bound CA protein. Alignment of multiple CA sequences illustrated that most of the putative active site residues of the pCAn isozyme were situated at highly conserved regions of the CA sequences. Examination of motif distribution suggested that the pCAn isozyme was very similar to the puffer predicted CA IV like isozyme. Reverse transcription-polymerase chain reaction (PCR) analysis showed highly differential expression in the brain, gills, kidney, and muscle, whereas CA mRNA expression was almost absent in heart, liver, and intestine. Quantitative PCR expression of CA mRNA abundance suggested several-fold higher expression of pCAn isozymes in the gills compared to other tissues tested. Our results suggest that the pCAn isozyme might be related to CA IV-like isozymes. Further functional studies are needed to investigate the function of the pCAn isozyme in T. vermicularis. PMID- 27188257 TI - Copy number variations in Hanwoo and Yanbian cattle genomes using the massively parallel sequencing data. AB - Hanwoo is an indigenous Korean beef cattle breed, and it shared an ancestor with Yanbian cattle that are found in the Northeast provinces in China until the last century. During recent decades, those cattle breeds experienced different selection pressures. Here, we present genome-wide copy number variations (CNVs) by comparing Hanwoo and Yanbian cattle sequencing data. We used ~3.12 and ~3.07 billion sequence reads from Hanwoo and Yanbian cattle, respectively. A total of 901 putative CNV regions (CNVRs) were identified throughout the genome, representing 5,513,340bp. This is a smaller number than has been reported in previous studies, indicating that Hanwoo are genetically close to Yanbian cattle. Of the CNVRs, 53.2% and 46.8% were found to be gains and losses in Hanwoo. Potential functional roles of each CNVR were assessed by annotating all CNVRs and gene ontology (GO) enrichment analysis. We found that 278 CNVRs overlapped with cattle gene-sets (genic-CNVRs) that could be promising candidates to account for economically important traits in cattle. The enrichment analysis indicated that genes were significantly over-represented in GO terms, including developmental process, multicellular organismal process, reproduction, and response to stimulus. These results provide a valuable genomic resource for determining how CNVs are associated with cattle traits. PMID- 27188258 TI - Self-assembly modified-mushroom nanocomposite for rapid removal of hexavalent chromium from aqueous solution with bubbling fluidized bed. AB - A self-assembled modified Pleurotus Cornucopiae material (SMPM) combined with improved Intermittent Bubbling Fluidized Bed (IBFB) was investigated to remove the hexavalent chromium ions in aqueous solution. After the modification, the powder-like raw material gradually self-assembled together to SMPM, which had crinkly porous structure, improved the Cr-accommodation ability in a sound manner. Optimized by Taguchi method, Cr(VI) removal efficiency was up to 75.91% and 48.01% for 100 mg/L and 500 mg/L initial concentration of Cr(VI), respectively. Results indicated that the metal removal was dependent on dosage of adsorbent, particle diameter and treatment time. The experimental data obtained from the biosorption process was successfully correlated with Freundlich isotherm model. Thermodynamic study indicated the endothermic nature of the process. The results confirmed that self-assembly modified Pleurotus Cornucopiae material could be applied for the removal of heavy metal from wastewater in continuous fluidized bed process. PMID- 27188260 TI - Case report: false positive elevated serum-galactomannan levels after autologous hematopoietic stem cell transplantation caused by oral nutritional supplements. AB - Positive galactomannan tests in patients who underwent chemotherapy without any clinical signs of a fungal infection should lead the clinician to consideration of a false-positive test result. Oral nutritional supplements may be a cause, especially in the case of concomitant disturbance of the gastrointestinal mucosal barrier because of mucositis. PMID- 27188259 TI - Midlife moderation-quantified healthy diet and 40-year mortality risk from CHD: the prospective National Heart, Lung, and Blood Institute Twin Study. AB - It is unknown whether influences of midlife whole diet on the long-term CHD mortality risk are independent of genetic and common environmental factors or familial predisposition. We addressed this question prospectively using data from the National Heart, Lung, and Blood Institute Twin Study. We included 910 male twins who were middle-aged and had usual diet assessed with nutritionist administered, cross-checked dietary history interview at baseline (1969-1973). Moderation-quantified healthy diet (MQHD), a dietary pattern, was created to evaluate a whole diet. Primary outcome was time-to-CHD death. Hazard ratios (HR) were estimated using frailty survival model. Known CHD risk factors were controlled. During the follow-up of 40 years through 31 December 2009, 113 CHD deaths, 198 total cardiovascular deaths and 610 all-cause deaths occurred. In the entire cohort, the multivariable-adjusted HR for the overall association (equivalent to a general population association) was 0.76 (95 % CI 0.66, 0.88) per 10-unit increment in the MQHD score for CHD, and the multivariable-adjusted HR for a twin with a MQHD score ten units higher than his co-twin brother was 0.79 (95 % CI 0.64, 0.96, P=0.02) for CHD independent of familial predisposition. Similar results were found for a slightly more food-specified alternative moderation-quantified healthy diet (aMQHD). The between-pair association (reflecting familial influence) was significant for CHD for both MQHD and aMQHD. It is concluded that associations of MQHD and aMQHD with a lower long-term CHD mortality risk are both nutritionally and familially affected, supporting their use for dietary planning to prevent CHD mortality. PMID- 27188261 TI - Follicular cell-derived thyroid cancer. AB - Follicular cell-derived thyroid cancers are derived from the follicular cells in the thyroid gland, which secrete the iodine-containing thyroid hormones. Follicular cell-derived thyroid cancers can be classified into papillary thyroid cancer (80-85%), follicular thyroid cancer (10-15%), poorly differentiated thyroid cancer (<2%) and undifferentiated (anaplastic) thyroid cancer (<2%), and these have an excellent prognosis with the exception of undifferentiated thyroid cancer. The advent and expansion of advanced diagnostic techniques has driven and continues to drive the epidemic of occult papillary thyroid cancer, owing to overdiagnosis of clinically irrelevant nodules. This transformation of the thyroid cancer landscape at molecular and clinical levels calls for the modification of management strategies towards personalized medicine based on individual risk assessment to deliver the most effective but least aggressive treatment. In thyroid cancer surgery, for instance, injuries to structures outside the thyroid gland, such as the recurrent laryngeal nerve in 2-5% of surgeries or the parathyroid glands in 5-10% of surgeries, negatively affect quality of life more than loss of the expendable thyroid gland. Furthermore, the risks associated with radioiodine ablation may outweigh the risks of persistent or recurrent disease and disease-specific mortality. Improvement in the health related quality of life of survivors of follicular cell-derived thyroid cancer, which is decreased despite the generally favourable outcome, hinges on early tumour detection and minimization of treatment-related sequelae. Future opportunities include more widespread adoption of molecular and clinical risk stratification and identification of actionable targets for individualized therapies. PMID- 27188262 TI - FGF19 and FGF21 serum concentrations in human obesity and type 2 diabetes behave differently after diet- or surgically-induced weight loss. AB - BACKGROUND & AIMS: Fibroblast growth factor 19 (FGF19) and 21 (FGF21) have emerged as key regulators of energy homeostasis. Our aim was to analyze the impact of weight loss (WL) induced either by conventional dietary treatment (CDT) or bariatric surgery on FGF19 and FGF21 concentrations. Furthermore, the diverse effect of sleeve gastrectomy (SG) versus RYGB (Roux-en-Y gastric bypass) as two surgical procedures that affect the gastrointestinal anatomy and physiology differently was also analyzed. METHODS: Serum concentrations of FGF19 and FGF21 were measured in 137 obese patients with different degrees of insulin resistance matched by sex, age and body adiposity and compared to 33 lean individuals. Furthermore, FGF19 and FGF21 were measured in 114 subjects before and one-year after WL induced either by CDT (n = 28), SG (n = 20) or RYGB (n = 66). RESULTS: Circulating serum FGF19 concentrations were decreased (P < 0.01) similarly in obese patients regardless of their degree of insulin resistance, while FGF21 levels were increased in obesity (P < 0.01), being further increased in obesity associated T2D (P < 0.01). FGF19 concentrations were increased in obese subjects after surgically-induced WL (P < 0.01), but not after WL achieved by CDT, while FGF21 levels were reduced after CDT- (P < 0.05) or SG-induced WL (P < 0.05), but not after RYGB. The change in FGF21 concentrations emerged as a significant predictor of the change in insulin resistance (HOMA) after WL. CONCLUSIONS: Based on the circulating concentrations and their subsequent pattern of response following WL, we conclude that FGF19 levels are mainly related to body adiposity, in particular visceral adiposity, while FGF21 is mainly related to glucose homeostasis. CLINICALTRIALS. GOV IDENTIFIER: NCT01572090. PMID- 27188263 TI - Blood product transfusions are associated with an increase in serum (1-3)-beta-d glucan in infants during the initial hospitalization in neonatal intensive care unit (NICU). AB - INTRODUCTION: Serum (1-3)-beta-d-glucan (BDG) assay has been proposed as an adjunct for the rapid diagnosis of invasive fungal infection (IFI). However, false-positive results have been reported following transfusion of blood products in adults. AIMS: To assess the relationship between blood product transfusion and elevated BDG in neonates. METHOD: Retrospective study including neonates <=32 weeks, with no fungal colonization or infection, in whom BDG assay was performed for suspicion of IFI. Patients were classified in Transfusion (n = 78) and No Transfusion (n = 55) groups depending on whether or not they were transfused. Clinical, biochemical and microbiological characteristics were recorded. A BDG assay >80 pg/mL was considered as positive. STATISTICAL ANALYSES: bivariate and multivariate logistic regression. Results (median, IQR): One hundred and thirty three infants were included (gestational age 28.4 weeks, 26.9-30; birth weight 1000 g, 847-1300). BDG was higher in the Transfusion group (170 pg/mL, 65-317) than in the No Transfusion group (57 pg/mL, 34-108; p < 0.001). False-positive BDG assay results were associated with red blood cells (RBC) and fresh frozen plasma (FFP) transfusions. CONCLUSION: BDG is increased after RBC and FFP transfusions in neonates, leading to overdiagnosis of IFI. Fungal colonization status in peripheral sites and central cultures could help to reduce the risk of misdiagnosis. PMID- 27188264 TI - When alcohol is the answer: Trapping, identifying and quantifying simple alkylating species in aqueous environments. AB - Alkylating agents are a significant class of environmental carcinogens as well as commonly used anticancer therapeutics. Traditional alkylating activity assays have utilized the colorimetric reagent 4-(4-nitrobenzyl)pyridine (4NBP). However, 4NBP based assays have a relatively low sensitivity towards harder, more oxophilic alkylating species and are not well suited for the identification of the trapped alkyl moiety due to adduct instability. Herein we describe a method using water as the trapping agent which permits the trapping of simple alkylating electrophiles with a comparatively wide range of softness/hardness and permits the identification of donated simple alkyl moieties. PMID- 27188265 TI - Flow cytometry combined with viSNE for the analysis of microbial biofilms and detection of microplastics. AB - Biofilms serve essential ecosystem functions and are used in different technical applications. Studies from stream ecology and waste-water treatment have shown that biofilm functionality depends to a great extent on community structure. Here we present a fast and easy-to-use method for individual cell-based analysis of stream biofilms, based on stain-free flow cytometry and visualization of the high dimensional data by viSNE. The method allows the combined assessment of community structure, decay of phototrophic organisms and presence of abiotic particles. In laboratory experiments, it allows quantification of cellular decay and detection of survival of larger cells after temperature stress, while in the field it enables detection of community structure changes that correlate with known environmental drivers (flow conditions, dissolved organic carbon, calcium) and detection of microplastic contamination. The method can potentially be applied to other biofilm types, for example, for inferring community structure for environmental and industrial research and monitoring. PMID- 27188268 TI - Sub-5 nm nanostructures fabricated by atomic layer deposition using a carbon nanotube template. AB - The fabrication of nanostructures having diameters of sub-5 nm is very a important issue for bottom-up nanofabrication of nanoscale devices. In this work, we report a highly controllable method to create sub-5 nm nano-trenches and nanowires by combining area-selective atomic layer deposition (ALD) with single walled carbon nanotubes (SWNTs) as templates. Alumina nano-trenches having a depth of 2.6 ~ 3.0 nm and SiO2 nano-trenches having a depth of 1.9 ~ 2.2 nm fully guided by the SWNTs have been formed on SiO2/Si substrate. Through infilling ZnO material by ALD in alumina nano-trenches, well-defined ZnO nanowires having a thickness of 3.1 ~ 3.3 nm have been fabricated. In order to improve the electrical properties of ZnO nanowires, as-fabricated ZnO nanowires by ALD were annealed at 350 degrees C in air for 60 min. As a result, we successfully demonstrated that as-synthesized ZnO nanowire using a specific template can be made for various high-density resistive components in the nanoelectronics industry. PMID- 27188267 TI - Comparative measurement and quantitative risk assessment of alcohol consumption through wastewater-based epidemiology: An international study in 20 cities. AB - Quantitative measurement of drug consumption biomarkers in wastewater can provide objective information on community drug use patterns and trends. This study presents the measurement of alcohol consumption in 20 cities across 11 countries through the use of wastewater-based epidemiology (WBE), and reports the application of these data for the risk assessment of alcohol on a population scale using the margin of exposure (MOE) approach. Raw 24-h composite wastewater samples were collected over a one-week period from 20 cities following a common protocol. For each sample a specific and stable alcohol consumption biomarker, ethyl sulfate (EtS) was determined by liquid chromatography coupled to tandem mass spectrometry. The EtS concentrations were used for estimation of per capita alcohol consumption in each city, which was further compared with international reports and applied for risk assessment by MOE. The average per capita consumption in 20 cities ranged between 6.4 and 44.3L/day/1000 inhabitants. An increase in alcohol consumption during the weekend occurred in all cities, however the level of this increase was found to differ. In contrast to conventional data (sales statistics and interviews), WBE revealed geographical differences in the level and pattern of actual alcohol consumption at an inter city level. All the sampled cities were in the "high risk" category (MOE<10) and the average MOE for the whole population studied was 2.5. These results allowed direct comparisons of alcohol consumption levels, patterns and risks among the cities. This study shows that WBE can provide timely and complementary information on alcohol use and alcohol associated risks in terms of exposure at the community level. PMID- 27188270 TI - Overview of short- and long-term tolerability and safety of brexpiprazole in patients with schizophrenia. AB - Second-generation antipsychotics have demonstrated efficacy for patients with schizophrenia but are associated with wide-ranging side effects. Brexpiprazole, a serotonin-dopamine activity modulator, has demonstrated efficacy in adult patients with schizophrenia. This paper provides an overview of the safety and tolerability of brexpiprazole in patients with schizophrenia through examination of pooled safety data from one Phase 2 and two Phase 3 6-week, short-term studies, and two open-label, 52-week, long-term studies. In the short-term studies, there were no reports of treatment-emergent adverse events (TEAEs) with an incidence>=5% and twice that of placebo in patients treated with brexpiprazole 2-4mg. In the long-term studies, TEAEs reported by >=5% of patients were schizophrenia (10.7%), insomnia (8.0%), weight increase (7.7%), headache (6.0%), and agitation (5.2%). Akathisia rates were low in the short- (5.8%, pooled brexpiprazole group) and long-term studies (4.6%). Sedation rates were low in the short- (2.3%, pooled brexpiprazole group) and long-term studies (0.9%). Mean body weight increase was 1.1kg in both short- and long-term studies. For all studies, changes from baseline to last visit in laboratory parameters, electrocardiogram values, and vital signs were small and not clinically relevant. Changes in lipid profiles or other metabolic parameters were also small. Collectively, these studies suggest that brexpiprazole was well tolerated, with a favorable safety profile that does not exhibit significant rates of important adverse events that can be seen with existing antipsychotics (akathisia, sedation, weight gain, or QTc prolongation), and therefore may provide a useful treatment option for patients with schizophrenia. ClinicalTrials.gov: NCT00905307; NCT01396421; NCT01393613; NCT01649557; NCT01397786. PMID- 27188271 TI - The stable isotope ecology of Pan in Uganda and beyond. AB - Stable isotope analysis has long been used to study the dietary ecology of living and fossil primates, and there has been increasing interest in using stable isotopes to study primate habitat use and anthropogenic impacts on non-human primates. Here, we examine the stable carbon and nitrogen isotope compositions of chimpanzees (Pan troglodytes) from seven communities in Uganda across a continuum of habitat structure (closed to more open) and access to anthropogenic resources (no reliance to heavy reliance). In general, the hair delta(13) C, but not delta(15) N, values of these communities vary depending on forest structure and degree of anthropogenic influence. When integrated with previously published hair delta(13) C and delta(15) N values for Pan, it is apparent that modern "savanna" and "forest" Pan form discrete clusters in carbon and nitrogen isotope space, although there are exceptions probably relating to microhabitat specialization. The combined dataset also reveals that Pan delta(13) C values (but not delta(15) N values) are inversely related to rainfall (r(2) = 0.62). We converted Pan hair delta(13) C values to enamel equivalents and made comparisons to the fossil hominoids Sivapithecus sp., Gigantopithecus blacki, Ardipithecus ramidus, and Australopithecus anamensis. The delta(13) C values of the fossil hominins Ar. ramidus and Au. anamensis do not cluster with the delta(13) C values of modern Pan in "forest" habitats, or with fossil hominoids that are believed to have inhabited forests. Am. J. Primatol. 78:1070-1085, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27188269 TI - What factors influence parents' perception of the quality of life of children and adolescents with neurocardiogenic syncope? AB - BACKGROUND: Health-related quality of life, which can be investigated using self reports or parental reports, could help healthcare providers understand the subjective perception of well-being of children suffering from recurrent syncopal episodes. Quality of life is not only a measure of health but is also a reflection of patients' and parents' perceptions and expectations of health. This study assessed: 1) the consistency and agreement between pediatric patients' self reports and parents' proxy-reports of their child's quality of life; 2) whether this patient-parent agreement is dependent on additional demographic and clinical or distress factors; 3) whether the parents' psychological distress influences children's and parents' responses to questionnaires on quality of life. METHODS: One hundred and twenty-five Italian children aged 6-18 years old (Mean age 12.75, SD 2.73, 48 % female) and their parents completed the Pediatric Quality of Life inventory with self-reports and parent-proxy reports, the Parenting Stress Index Short Form questionnaire and the Child Behavior Checklist for ages 6-18. Patients' and parents' scores on quality of life were analyzed via an intra-class correlation coefficient, Spearman's correlation coefficient, Wilcoxon signed-rank test, and Bland-Altman plot. RESULTS: Child-rated quality of life was lower than parent-rated quality of life. However, there were no statistically significant differences between pediatric patients' self-reports and their parents' proxy reports of on quality of life. Clinically significant patient-parent variation in pediatric health-related quality of life was observed. Differences in patient parent proxy Pediatric Quality of Life inventory Total Scale Score scores were significantly associated with patient age. CONCLUSION: Concerning parents' proxy ratings of their children's quality of life on the Pediatric Quality of Life inventory, parental stress was found to be negatively associated with their perceptions of their child's psychological quality of life. Indeed, childhood illness is a source of stress for the whole family, and exposes family members to a greater risk of developing psychosocial difficulties. In conclusion, this study invites reflection on the use of cross-informants in investigating the quality of life of young patients with neurocardiogenic syncope and the psychological factors that influence how quality of life is perceived. PMID- 27188272 TI - A case-control study evaluating the role of internet meet-up sites and mobile telephone applications in influencing a syphilis outbreak: Multnomah County, Oregon, USA 2014. AB - OBJECTIVES: Early syphilis in Multnomah County, Oregon, USA, increased 16-fold during 2007-2013. Cases predominantly occurred among men who have sex with men (MSM); 55% were HIV coinfected. We conducted a case-control study to evaluate the association between meeting sex partners online and early syphilis. METHODS: Cases subjects (cases) were Multnomah County resident, English speaking, MSM, aged >=18 years with laboratory-confirmed early syphilis reported 1 January to 31 December 2013. We recruited two MSM controls subjects (controls) per case, frequency matched by HIV status and age. Participants completed self-administered questionnaires. We performed multivariable logistic regression. RESULTS: Seventy per cent (40/57) of cases and 42% (50/119) of controls met partners online (p<0.001). Cases more frequently met partners online (adjusted OR (aOR)=3.0; 95% CI 1.2 to 6.7), controlling for presumptive confounders. Cases reported more partners than controls (medians 5, 2; p<0.001). When including number of partners, aOR decreased to 1.4 (95% CI 0.5 to 3.9). CONCLUSIONS: Early syphilis was associated with meeting partners online. We believe this association may be related to number of sex partners acting as an intermediate variable between use of online resources to meet sex partners and early syphilis. Online meet-up sites might represent areas for public health interventions targeting at-risk individuals. PMID- 27188273 TI - Vaginal high-risk human papillomavirus infection in a cross-sectional study among women of six different ethnicities in Amsterdam, the Netherlands: the HELIUS study. AB - OBJECTIVE: In the Netherlands the incidence of cervical cancer is higher among ethnic minority populations compared with the general Dutch population. We investigated the prevalence of, and risk factors associated with, vaginal high risk human papillomavirus (hrHPV) infection in women of six different ethnicities living in Amsterdam. METHODS: For this cross-sectional study we selected women aged 18-34 years old of six ethnicities from the large-scale multiethnic HEalthy LIfe in an Urban Setting study. Self-collected vaginal swabs were tested for HPV DNA and genotyped using a highly sensitive PCR and reverse line blot assay (short PCR fragment (SPF)10-PCR DNA enzyme immunoassay/LiPA25-system version-1, delft diagnostic laboratory (DDL)). Participants completed a questionnaire regarding demographics and sexual behaviour. Logistic regression using generalised estimating equations was used to assess risk factors of hrHPV, and to investigate whether prevalence of hrHPV differed among ethnicities. RESULTS: The study population consisted of 592 women with a median age of 27 (IQR: 23-31) years. Dutch and African Surinamese women reported the highest sexual risk behaviour. HrHPV prevalence was highest in the Dutch (40%) followed by the African Surinamese (32%), Turkish (29%), Ghanaian (26%), Moroccan (26%) and South-Asian Surinamese (18%). When correcting for sexual risk behaviour, the odds to be hrHPV positive were similar for all non-Dutch groups when compared with that of the Dutch group. CONCLUSIONS: We found an overall higher hrHPV prevalence and higher sexual risk behaviour in the native Dutch population. Further research is needed to unravel the complex problem concerning cervical cancer disparities, such as differences in participation in the cervical cancer screening programme, or differences in clearance and persistence of hrHPV. PMID- 27188275 TI - Current concepts of Harm-Benefit Analysis of Animal Experiments - Report from the AALAS-FELASA Working Group on Harm-Benefit Analysis - Part 1. AB - International regulations and guidelines strongly suggest that the use of animal models in scientific research should be initiated only after the authority responsible for the review of animal studies has concluded a well-thought-out harm-benefit analysis (HBA) and deemed the project to be appropriate. Although the process for conducting HBAs may not be new, the relevant factors and algorithms used in conducting them during the review process are deemed to be poorly defined or lacking by committees in many institutions. This paper presents the current concept of HBAs based on a literature review. References on cost or risk benefit from clinical trials and other industries are also included. Several approaches to HBA have been discovered including algorithms, graphic presentations and generic processes. The aim of this study is to better aid and harmonize understanding of the concepts of 'harm', 'benefit' and 'harm-benefit analysis'. PMID- 27188274 TI - Adoptive immunotherapy against ovarian cancer. AB - The standard front-line therapy for epithelial ovarian cancer (EOC) is combination of debulking surgery and platinum-based chemotherapy. Nevertheless, the majority of patients experience disease recurrence. Although extensive efforts to find new therapeutic options, cancer cells invariably develop drug resistance and disease progression. New therapeutic strategies are needed to improve prognosis of patients with advanced EOC.Recently, several preclinical and clinical studies investigated feasibility and activity of adoptive immunotherapy in EOC. Our aim is to highlight prospective of adoptive immunotherapy in EOC, focusing on HLA-restricted Tumor Infiltrating Lymphocytes (TILs), and MHC independent immune effectors such as natural killer (NK), and cytokine-induced killer (CIK). Adoptive cell therapy (ACT) has shown activity in several pre clinical models. Available preclinical and clinical data suggest that adoptive cell therapy may provide the best benefit in settings of low tumor burden, minimal residual disease, or maintenance therapy. Further studies are needed to better define the optimal clinical setting. PMID- 27188276 TI - Recommendations for Addressing Harm-Benefit Analysis and Implementation in Ethical Evaluation - Report from the AALAS-FELASA Working Group on Harm-Benefit Analysis - Part 2. AB - International regulations and guidelines strongly suggest that the use of animal models in scientific research should be initiated only after the authority responsible for the review of animal studies has concluded a well-thought-out harm-benefit analysis (HBA) and deemed the project to be appropriate. The AALAS FELASA working group on HBA has performed a literature review and based on this review, proposed a method for HBA. Examples of the working group's approach are included in this report. PMID- 27188278 TI - Response to: Pleural mesothelioma, and occupational and non-occupational asbestos exposure: a case-control study with quantitative risk assessment. PMID- 27188277 TI - Domains of cognitive function in early old age: which ones are predicted by pre retirement psychosocial work characteristics? AB - BACKGROUND: Psychosocial work characteristics may predict cognitive functioning after retirement. However, little research has explored specific cognitive domains associated with psychosocial work environments. Our study tested whether exposure to job demands, job control and their combination during working life predicted post-retirement performance on eight cognitive tests. METHODS: We used data from French GAZEL cohort members who had undergone post-retirement cognitive testing (n=2149). Psychosocial job characteristics were measured on average for 4 years before retirement using Karasek's Job Content Questionnaire (job demands, job control and demand-control combinations). We tested associations between these exposures and post-retirement performance on tests for executive function, visual-motor speed, psychomotor speed, verbal memory, and verbal fluency using ordinary least squares regression. RESULTS: Low job control during working life was negatively associated with executive function, psychomotor speed, phonemic fluency and semantic fluency after retirement (p's<0.05), even after adjustment for demographics, socioeconomic status, health and social behaviours and vascular risk factors. Both passive (low-demand, low-control) and high-strain (high demand, low-control) jobs were associated with lower scores on phonemic and semantic fluency when compared to low-strain (low-demand, high-control) jobs. CONCLUSIONS: Low job control, in combination with both high and low-job demands, is associated with post-retirement deficits in some, but not all, cognitive domains. In addition to work stress, associations between passive work and subsequent cognitive function may implicate lack of cognitive engagement at work as a risk factor for future cognitive difficulties. PMID- 27188279 TI - Risk assessment of di(2-ethylhexyl) phthalate in the workplace. AB - OBJECTIVES: A hazard assessment of di(2-ethylhexyl) phthalate (DEHP), a commonly used workplace chemical, was conducted in order to protect the occupational health of workers. A literature review, consisting of both domestic and international references, examined the chemical management system, working environment, level of exposure, and possible associated risks. This information may be utilized in the future to determine appropriate exposure levels in working environments. METHODS: Hazard assessment was performed using chemical hazard information obtained from international agencies, such as Organization for Economic Cooperation and Development-generated Screening Information Data Set and International Program on Chemical Safety. Information was obtained from surveys conducted by the Minister of Employment and Labor ("Survey on the work environment") and by the Ministry of Environment ("Survey on the circulation amount of chemicals"). Risk was determined according to exposure in workplaces and chemical hazard. RESULTS: In 229 workplaces over the country, 831 tons of DEHP have been used as plasticizers, insecticides, and ink solvent. Calculated 50% lethal dose values ranged from 14.2 to 50 g/kg, as determined via acute toxicity testing in rodents. Chronic carcinogenicity tests revealed cases of lung and liver degeneration, shrinkage of the testes, and liver cancer. The no observed-adverse-effect level and the lowest-observed-adverse-effect level were determined to be 28.9 g/kg and 146.6 g/kg, respectively. The working environment assessment revealed the maximum exposure level to be 0.990 mg/m(3), as compared to the threshold exposure level of 5 mg/m(3). The relative risk of chronic toxicity and reproductive toxicity were 0.264 and 0.330, respectively, while the risk of carcinogenicity was 1.3, which is higher than the accepted safety value of one. CONCLUSIONS: DEHP was identified as a carcinogen, and may be dangerous even at concentrations lower than the occupational exposure limit. Therefore, we suggest management of working environments, with exposure levels below 5 mg/m(3) and all workers utilizing local exhaust ventilation and respiratory protection when handling DEHP. PMID- 27188280 TI - The effects of the standardized extracts of Ginkgo biloba on steroidogenesis pathways and aromatase activity in H295R human adrenocortical carcinoma cells. AB - OBJECTIVES: Aromatase inhibitors that block estrogen synthesis are a proven first line hormonal therapy for postmenopausal breast cancer. Although it is known that standardized extract of Ginkgo biloba (EGb761) induces anti-carcinogenic effects like the aromatase inhibitors, the effects of EGb761 on steroidogenesis have not been studied yet. Therefore, the effects of EGb761 on steroidogenesis and aromatase activity was studied using a H295R cell model, which was a good in vitro model to predict effects on human adrenal steroidogenesis. METHODS: Cortisol, aldosterone, testosterone, and 17beta-estradiol were evaluated in the H295R cells by competitive enzyme-linked immunospecific assay after exposure to EGb761. Real-time polymerase chain reaction were performed to evaluate effects on critical genes in steroid hormone production, specifically cytochrome P450 (CYP11/ 17/19/21) and the hydroxysteroid dehydrogenases (3beta-HSD2 and 17beta HSD1/4). Finally, aromatase activities were measured with a tritiated water release assay and by western blotting analysis. RESULTS: H295R cells exposed to EGb761 (10 and 100 MUg/mL) showed a significant decrease in 17beta-estradiol and testosterone, but no change in aldosterone or cortisol. Genes (CYP19 and 17beta HSD1) related to the estrogen steroidogenesis were significantly decreased by EGb761. EGb761 treatment of H295R cells resulted in a significant decrease of aromatase activity as measured by the direct and indirect assays. The coding sequence/ Exon PII of CYP19 gene transcript and protein level of CYP19 were significantly decreased by EGb761. CONCLUSIONS: These results suggest that EGb761 could regulate steroidogenesis-related genes such as CYP19 and 17beta-HSD1, and lead to a decrease in 17beta-estradiol and testosterone. The present study provides good information on potential therapeutic effects of EGb761 on estrogen dependent breast cancer. PMID- 27188283 TI - A new electrochemical aptasensor based on a dual-signaling strategy and supersandwich assay. AB - In this study, we develop a new electrochemical aptasensor by coupling two amplification strategies, including a dual signaling strategy and a supersandwich assay. In order to fabricate this aptasensor, a thiolated capture probe (CP) was first self-assembled on the gold electrode surface by Au-S bonds. After the addition of methylene blue (MB) modified signal probe 1 (SP1) and ferrocene (Fc) labeled signal probe 2 (SP2), supersandwich structure DNA, including multiple units of SP1 and SP2, was grown from the CP on the electrode surface. In the presence of ATP, the strong interaction between ATP and its aptamer (CP, SP1) leads to the disassembly of the supersandwich structure and thereby, the release of SP1 and SP2 from the gold electrode surface, resulting in a decrease of the MB and Fc signals. Taking "Signal gainMB + Signal gainFc" as the response signal, ATP can be detected sensitively; the detection limit is 2.1 nM, which is lower than that using either a single-signaling strategy or a traditional sandwich assay alone. Moreover, the new aptasensor also exhibits excellent specificity, selectivity, reliability and applicability. We believe that this new strategy will be helpful for fabricating sensitive and selective electrochemical aptasensors of other biomolecules and small molecules. PMID- 27188281 TI - Betulinic acid synergically enhances BMP2-induced bone formation via stimulating Smad 1/5/8 and p38 pathways. AB - BACKGROUND: Healing of bone defects is a dynamic and orchestrated process that relies on multiple growth factors and cell types. Bone morphogenetic protein 2 (BMP2) is a key growth factor for bone healing, which stimulates mesenchymal stem cells to differentiate into osteoblasts. Betulinic acid (BetA) is a natural pentacyclic triterpenoid from plants. This study aimed to examine combinatory effects of BetA and BMP2 on ectopic bone generation in mice. RESULTS: In MC3T3-E1 preosteoblast culture, 10-15 MUM of BetA increased the alkaline phosphatase (ALP) activity and expression levels of osteogenic marker genes without the decreased cell viability. In addition, BetA synergistically enhanced BMP2-induced gene expressions and mineralization with the enhancement of phosphorylation of Smad1/5/8 and p38. In an in vivo ectopic bone formation model, combination of BetA (50 MUg) and BMP2 (3 MUg) resulted in increases in the amount of new bone generation, compared with treatment with BMP2 alone. Histological studies showed that bone generation with cortical and trabecular structures was resulted from the combination of BetA and BMP2. CONCLUSION: BetA can enhance in vivo osteogenic potentials of BMP2, possibly via stimulating Smad 1/5/8 and p38 pathways, and combination of both agents can be considered as a therapeutic strategy for bone diseases. PMID- 27188282 TI - Epigenetically maintained SW13+ and SW13- subtypes have different oncogenic potential and convert with HDAC1 inhibition. AB - BACKGROUND: The BRM and BRG1 tumor suppressor genes are mutually exclusive ATPase subunits of the SWI/SNF chromatin remodeling complex. The human adrenal carcinoma SW13 cell line can switch between a subtype which expresses these subunits, SW13+, and one that expresses neither subunit, SW13-. Loss of BRM expression occurs post-transcriptionally and can be restored via histone deacetylase (HDAC) inhibition. However, most previously used HDAC inhibitors are toxic and broad spectrum, providing little insight into the mechanism of the switch between subtypes. In this work, we explore the mechanisms of HDAC inhibition in promoting subtype switching and further characterize the oncogenic potential of the two epigenetically distinct SW13 subtypes. METHODS: SW13 subtype morphology, chemotaxis, growth rates, and gene expression were assessed by standard immunofluorescence, transwell, growth, and qPCR assays. Metastatic potential was measured by anchorage-independent growth and MMP activity. The efficacy of HDAC inhibitors in inducing subtype switching was determined by immunofluorescence and qPCR. Histone modifications were assessed by western blot. RESULTS: Treatment of SW13- cells with HDAC1 inhibitors most effectively promotes re-expression of BRM and VIM, characteristic of the SW13+ phenotype. During treatment, hyperacetylation of histone residues and hypertrimethylation of H3K4 is pronounced. Furthermore, histone modification enzymes, including HDACs and KDM5C, are differentially expressed during treatment but several features of this differential expression pattern differs from that seen in the SW13- and SW13+ subtypes. As the SW13- subtype is more proliferative while the SW13+ subtype is more metastatic, treatment with HDACi increases the metastatic potential of SW13 cells while restoring expression of the BRM tumor suppressor. CONCLUSIONS: When compared to the SW13- subtype, SW13+ cells have restored BRM expression, increased metastatic capacity, and significantly different expression of a variety of chromatin remodeling factors including those involved with histone acetylation and methylation. These data are consistent with a multistep mechanism of SW13- to SW13+ conversion and subtype stabilization: histone hypermodification results in the altered expression of chromatin remodeling factors and chromatin epigenetic enzymes and the re-expression of BRM which results in restoration of SWI/SNF complex function and leads to changes in chromatin structure and gene expression that stabilize the SW13+ phenotype. PMID- 27188287 TI - A molecular dynamics study of the ionic liquid, choline acetate. AB - Structural and dynamic properties of the ionic liquid (IL) choline acetate are studied using molecular dynamics (MD) simulations. The hydroxyl group of choline shows significant hydrogen-bonding interactions with the oxygen atoms of acetate. Nearly all choline cations are found to form a hydrogen bond with acetate anions at 400 K, while about 67% of cations participate in hydrogen-bonding interactions at 600 K. At 400 K, subdiffusive and prominent non-Gaussian behavior persist for t > 10 ns. At 600 K, the usual diffusion regime is obtained after a few hundred ps of subdiffusive behavior. Analysis of reorientational motions of acetate ions, particularly those of their short axes, indicates a high degree of dynamic heterogeneity, in agreement with previous work on different IL systems. PMID- 27188286 TI - Long non-coding RNA expression profile in minor salivary gland of primary Sjogren's syndrome. AB - BACKGROUND: To examine the roles of long noncoding RNAs (lncRNAs) in the regulation of primary Sjogren's syndrome (pSS) and reveal the expression profile of lncRNAs in labial salivary glands (LSGs) in pSS patients. METHOD: The expression of 63,431 lncRNAs and 39,887 mRNAs were determined in the LSG of four pSS patients and four healthy controls using microarray experiments. Validation was performed in 30 pSS patients and 16 controls using real-time PCR. LncRNA-mRNA co-expression and gene-pathway networks were constructed using bioinformatics software. RESULT: A total of 1243 lncRNAs (upregulated: 890, downregulated: 353) and 1457 mRNAs (upregulated: 1141, downregulated: 316) were differentially expressed in the LSGs of pSS patients (fold change >2, P <0.05). Eight of these lncRNAs were validated using real-time PCR. ENST00000420219.1 (3.13-fold), ENST00000455309.1 (2.51-fold), n336161 (2.45-fold), NR_002712 (2.41-fold), ENST00000546086.1 (1.94-fold), Lnc-UTS2D-1:1 (1.79-fold), n340599 (1.69-fold), and TCONS_l2_00014794 (1.28-fold) were significantly upregulated in pSS. There were strong correlations between these lncRNAs and beta2 microglobulin, disease course, erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), IgA, IgM, visual analogue scale (VAS) of parotid swelling and VAS of dry eyes. Computational analyses revealed that 28 of the differentially expressed (DE) mRNAs were associated with eight DE lncRNAs involved in chemokine signaling pathways, the nuclear factor-kappa B (NF-kappaB) signaling pathway, and tumor necrosis factor (TNF) signaling pathway. CONCLUSIONS: Our study revealed the expression profile of lncRNAs in LSGs of pSS patients. Many novel lncRNA transcripts that play important roles in the pathogenesis of pSS were dysregulated in pSS. Therefore, this study will aid in the development of new diagnostic biomarkers and drug therapies. PMID- 27188284 TI - Polyglutamine androgen receptor-mediated neuromuscular disease. AB - An expanded polyglutamine (polyQ) tract at the amino-terminus of the androgen receptor (AR) confers toxic properties responsible for neuronal and non-neuronal degeneration in spinal and bulbar muscular atrophy (SBMA), one of nine polyQ expansion diseases. Both lower motor neurons and peripheral tissues, including skeletal muscle, are affected, supporting the notion that SBMA is not a pure motor neuron disease but a degenerative disorder of the neuromuscular system. Here, we review experimental evidence demonstrating both nerve and muscle degeneration in SBMA model systems and patients. We propose that polyQ AR toxicity targets these components in a time-dependent fashion, with muscle pathology predominating early and motor neuron loss becoming more significant at late stages. This model of pathogenesis has important therapeutic implications, suggesting that symptoms arising from degeneration of nerve or muscle predominate at different points and that directed interventions targeting these components will be variably effective depending upon disease progression. PMID- 27188288 TI - Biochemical indications of cerebral ischaemia and mitochondrial dysfunction in severe brain trauma analysed with regard to type of lesion. AB - BACKGROUND: The study focuses on three questions related to the clinical usefulness of microdialysis in severe brain trauma: (1) How frequently is disturbed cerebral energy metabolism observed in various types of lesions? (2) How often does the biochemical pattern indicate cerebral ischaemia and mitochondrial dysfunction? (3) How do these patterns relate to mortality? METHOD: The study includes 213 consecutive patients with severe brain trauma (342 intracerebral microdialysis catheters). The patients were classified into four groups according to the type of lesion: extradural haematoma (EDH), acute subdural haematoma (SDH), cerebral haemorrhagic contusion (CHC) and no mass lesion (NML). Altogether about 150,000 biochemical analyses were performed during the initial 96 h after trauma. RESULTS: Compromised aerobic metabolism occurred during 38 % of the study period. The biochemical pattern indicating mitochondrial dysfunction was more common than that of ischaemia. In EDH and NML aerobic metabolism was generally close to normal. In SDH or CHC it was often severely compromised. Mortality was increased in SDH with impaired aerobic metabolism, while CHC did not exhibit a similar relation. CONCLUSIONS: Compromised energy metabolism is most frequent in patients with SDH and CHC (32 % and 49 % of the study period, respectively). The biochemical pattern of mitochondrial dysfunction is more common than that of ischaemia (32 % and 6 % of the study period, respectively). A correlation between mortality and biochemical data is obtained provided the microdialysis catheter is placed in an area where energy metabolism reflects tissue outcome in a large part of the brain. PMID- 27188285 TI - Stress transgenerationally programs metabolic pathways linked to altered mental health. AB - Stress is among the primary causes of mental health disorders, which are the most common reason for disability worldwide. The ubiquity of these disorders, and the costs associated with them, lends a sense of urgency to the efforts to improve prediction and prevention. Down-stream metabolic changes are highly feasible and accessible indicators of pathophysiological processes underlying mental health disorders. Here, we show that remote and cumulative ancestral stress programs central metabolic pathways linked to mental health disorders. The studies used a rat model consisting of a multigenerational stress lineage (the great-great grandmother and each subsequent generation experienced stress during pregnancy) and a transgenerational stress lineage (only the great-great-grandmother was stressed during pregnancy). Urine samples were collected from adult male F4 offspring and analyzed using 1H NMR spectroscopy. The results of variable importance analysis based on random variable combination were used for unsupervised multivariate principal component analysis and hierarchical clustering analysis, as well as metabolite set enrichment analysis (MSEA) and pathway analysis. We identified distinct metabolic profiles associated with the multigenerational and transgenerational stress phenotype, with consistent upregulation of hippurate and downregulation of tyrosine, threonine, and histamine. MSEA and pathway analysis showed that these metabolites are involved in catecholamine biosynthesis, immune responses, and microbial host interactions. The identification of metabolic signatures linked to ancestral programming assists in the discovery of gene targets for future studies of epigenetic regulation in pathogenic processes. Ultimately, this research can lead to biomarker discovery for better prediction and prevention of mental health disorders. PMID- 27188289 TI - Tyrosinemia type 1 and irreversible neurologic crisis after one month discontinuation of nitisone. AB - Tyrosinemia type I is an autosomal recessively inherited metabolic disease of tyrosine metabolism due to the deficiency of fumarylacetoacetate hydrolase. Clinical manifestations include hepatic failure, cirrhosis, hepatocellular carcinoma, renal fanconi syndrome, and neurologic crisis. With the introduction of 2-(2-nitro-4-trifluoro-methylbenzyol)-1,3 cyclohexanedione treatment the prognosis improved with reduced rate of complications. "Neurologic crisis" of tyrosinemia type I is a rare complication seen after discontinuation of treatment characterized with anorexia, vomiting, and hyponatremia in the initial phase continuing with paresthesia and paralysis of the extremities and the diaphragm. Here, we report a tyrosinemia type I patient who admitted to the hospital with nonspecific symptoms such as vomiting, anorexia, weakness, and restlessness only after one month discontinuation of nitisone and diagnosed as neurological crisis. PMID- 27188290 TI - Rhizophora mucronata attenuates beta-amyloid induced cognitive dysfunction, oxidative stress and cholinergic deficit in Alzheimer's disease animal model. AB - Alzheimer's disease (AD) is a progressive neurodegenerative disorder, characterized by accumulation and deposition of Abeta peptide in human brain. The present study aimed to determine the protective effect of catechin rich extract of MERM (methanolic extract of Rhizophora mucronata) on Abeta (25-35) induced cognitive impairment and neuronal toxicity in mice. In the present study AD characteristics were induced by intracerberoventricular administration of aggregated Abeta (25-35) in the Swiss albino mice. Learning and memory deficits were assessed using behavioral assays such as Morris water maze, Y-maze and step down avoidance tasks. Oxidative stress mediated impairment were assessed by measuring the activities of enzymatic and non-enzymatic antioxidants, level of apoptotic protein and oxidative markers in the hippocampus and frontal cortex region. Histolopathological analysis of brain was also carried out. Results illustrated that oral treatment of MERM (200 and 400 mg/kg bw) significantly attenuated Abeta (25-35) induced memory impairment as evaluated by behavioral tests. In addition treatment with MERM attenuated the elevation of beta-secretase activity accompanying the reduced level of Abeta (25-35) in the cortex and hippocampus of brain. MERM also enhanced the cognitive function by significantly inhibiting AChE, BuChE and MAO-B. Furthermore, MERM attenuated lipid peroxidation, protein oxidation, restored the antioxidant status and inhibited neuronal apoptosis by down-regulating the level of caspase 3 and Bax protein. These data suggest that MERM rich in catechin can act as promising drug for AD treatment because of its antioxidant, anti-apoptotic and reducing Abeta oligomer activities. PMID- 27188292 TI - (1)H, (15)N, (13)C resonance assignments for Saccharomyces cerevisiae Rad23 UBL domain. AB - Rad23 functions in nucleotide excision repair and proteasome-mediated protein degradation. It has four distinct structural domains that are connected by flexible linker regions, including an N-terminal ubiquitin-like (UBL) domain that binds proteasomes. We report in this NMR study the (1)H, (15)N and (13)C resonance assignments for the backbone and side chain atoms of the Rad23 UBL domain (Rad23(UBL)) with BioMagResBank accession number 25825. We find that a Rad23 proline amino acid (P20) located in a loop undergoes isomerization. The secondary structural elements predicted from the NMR data fit well to that of the Rad23(UBL) when complexed with E4 ubiquitin ligase Ufd2, as reported in a crystallographic structure. These complete assignments can be used to study the protein dynamics of the Rad23(UBL) and its interaction of with other ubiquitin receptors or proteasome subunits. PMID- 27188291 TI - Loss of NCB5OR in the cerebellum disturbs iron pathways, potentiates behavioral abnormalities, and exacerbates harmaline-induced tremor in mice. AB - Iron dyshomeostasis has been implicated in many diseases, including a number of neurological conditions. Cytosolic NADH cytochrome b5 oxidoreductase (NCB5OR) is ubiquitously expressed in animal tissues and is capable of reducing ferric iron in vitro. We previously reported that global gene ablation of NCB5OR resulted in early-onset diabetes and altered iron homeostasis in mice. To further investigate the specific effects of NCB5OR deficiency on neural tissue without contributions from known phenotypes, we generated a conditional knockout (CKO) mouse that lacks NCB5OR only in the cerebellum and midbrain. Assessment of molecular markers in the cerebellum of CKO mice revealed changes in pathways associated with cellular and mitochondrial iron homeostasis. (59)Fe pulse-feeding experiments revealed cerebellum-specific increased or decreased uptake of iron by 7 and 16 weeks of age, respectively. Additionally, we characterized behavioral changes associated with loss of NCB5OR in the cerebellum and midbrain in the context of dietary iron deprivation-evoked generalized iron deficiency. Locomotor activity was reduced and complex motor task execution was altered in CKO mice treated with an iron deficient diet. A sucrose preference test revealed that the reward response was intact in CKO mice, but that iron deficient diet consumption altered sucrose preference in all mice. Detailed gait analysis revealed locomotor changes in CKO mice associated with dysfunctional proprioception and locomotor activation independent of dietary iron deficiency. Finally, we demonstrate that loss of NCB5OR in the cerebellum and midbrain exacerbated harmaline-induced tremor activity. Our findings suggest an essential role for NCB5OR in maintaining both iron homeostasis and the proper functioning of various locomotor pathways in the mouse cerebellum and midbrain. PMID- 27188293 TI - Genetic manipulation of putrescine biosynthesis reprograms the cellular transcriptome and the metabolome. AB - BACKGROUND: With the increasing interest in metabolic engineering of plants using genetic manipulation and gene editing technologies to enhance growth, nutritional value and environmental adaptation, a major concern is the potential of undesirable broad and distant effects of manipulating the target gene or metabolic step in the resulting plant. A comprehensive transcriptomic and metabolomic analysis of the product may shed some useful light in this regard. The present study used these two techniques with plant cell cultures to analyze the effects of genetic manipulation of a single step in the biosynthesis of polyamines because of their well-known roles in plant growth, development and stress responses. RESULTS: The transcriptomes and metabolomes of a control and a high putrescine (HP) producing cell line of poplar (Populus nigra x maximowiczii) were compared using microarrays and GC/MS. The HP cells expressed an ornithine decarboxylase transgene and accumulated several-fold higher concentrations of putrescine, with only small changes in spermidine and spermine. The results show that up-regulation of a single step in the polyamine biosynthetic pathway (i.e. ornithine -> putrescine) altered the expression of a broad spectrum of genes; many of which were involved in transcription, translation, membrane transport, osmoregulation, shock/stress/wounding, and cell wall metabolism. More than half of the 200 detected metabolites were significantly altered (p <= 0.05) in the HP cells irrespective of sampling date. The most noteworthy differences were in organic acids, carbohydrates and nitrogen-containing metabolites. CONCLUSIONS: The results provide valuable information about the role of polyamines in regulating nitrogen and carbon use pathways in cell cultures of high putrescine producing transgenic cells of poplar vs. their low putrescine counterparts. The results underscore the complexity of cellular responses to genetic perturbation of a single metabolic step related to nitrogen metabolism in plants. Combined with recent studies from our lab, where we showed that higher putrescine production caused an increased flux of glutamate into ornithine concurrent with enhancement in glutamate production via additional nitrogen and carbon assimilation, the results from this study provide guidance in designing transgenic plants with increased nitrogen use efficiency, especially in plants intended for non-food/feed applications (e.g. increased biomass production for biofuels). PMID- 27188296 TI - Hepatic Resection for Metastatic Neuroendocrine Cancer in Patients with Bone Metastases. AB - BACKGROUND: Hepatic resection (HR) of metastatic neuroendocrine cancer has been associated with prolonged survival and durable symptom control for selected patients with metastatic neuroendocrine tumor (NET). The present study investigates the outcomes of this operative approach in selected patients with known bone metastases. METHODS: All patients undergoing HR at Mayo Clinic Rochester and Mayo Clinic Florida for metastatic NET between January 1989 and August 2015 were identified, and were divided into two groups: those undergoing HR with a known diagnosis of bone metastases (HRmNET/LB) and those who had metastatic disease confined to the liver (HRmNET/L). RESULTS: A total of 25 patients in the HRmNET/LB group were propensity matched with 100 patients in the HRmNET/L group. Major liver resection was performed in 60 % of patients in the HRmNET/LB group and 55 % of patients in the HRmNET/L group (p = 0.42). Median survival for the HRmNET/LB group was 54.0 months, compared with 97.7 months for the HRmNET/L group (p = 0.03). In the HRmNET/LB group, median survival was 73.3 months for patients with gastrointestinal NET(GNET), compared with 42.7 months for patients with pancreatic NET (PNET). The median number of bone metastases was 2 (range 1-10), and the sites of bone metastases were the spine (68 %), pelvis (24 %), and ribs (12 %). Bone metastases were treated with radiotherapy in ten (40 %) patients, by radiofrequency ablation in two (8 %) patients, and by resection in one (4 %) patient. CONCLUSIONS: The present study is the first report to describe HR for patients with metastatic NET and known bone metastases. We demonstrated that in properly selected cases, excellent survival can be achieved with liver debulking in these patients. PMID- 27188294 TI - The two-component signal transduction system YvcPQ regulates the bacterial resistance to bacitracin in Bacillus thuringiensis. AB - YvcPQ is one of the two-component signal transduction systems that respond to specific stimuli and enable cells to adjust multiple cellular functions. It consists of a histidine kinase YvcQ and a response regulator YvcP. In this study, through searching the consensus sequence recognized by YvcP, we found four YvcP binding motifs in the promoter regions of genes yvcR (BMB171_C4100), BMB171_C4385, kapD (BMB171_C4525) and BMB171_C4835 in Bacillus thuringiensis BMB171 which is a representative of Bacillus cereus group, and confirmed that these genes are regulated by YvcP. We compared the sequence of yvcPQ and its downstream genes in genus Bacillus, and found two different kinds of yvc locus, one was the yvcPQ-RS in B. subtilis species and the other was the yvcPQ-R-S1S2 in B. cereus group. Furthermore, we found that YvcP activates the transcription of yvcS1S2 (downstream of yvcR) to promote bacterial resistance to bacitracin and deletion of either yvcPQ operon or yvcS1S2 operon renders the bacterial cells more sensitive to bacitracin. This study enriched our understanding of both the YvcPQ's function and the mechanism of bacterial resistance to bacitracin. PMID- 27188295 TI - Incidence and Risk Factors for Occult Level 3 Lymph Node Metastases in Papillary Thyroid Cancer. AB - BACKGROUND: Papillary thyroid cancer (PTC) frequently disseminates into cervical lymph nodes. Lateral node involvement is described in up to 50 % patients undergoing prophylactic lateral neck dissection. This study aimed to assess this finding and identify which factors predict for occult lateral node disease. METHODS: Patients with fine needle aspiration-confirmed PTC (Bethesda V or VI), without evidence of cervical lymph node metastases, underwent a total thyroidectomy with prophylactic ipsilateral central and level 3 dissection. Level 3 nodes were removed by compartmental dissection or by sampling the sentinel nodes overlying the jugular vein, according to surgeon preference. Data were collected prospectively from January 2011 to August 2014. Statistical analysis was performed by SPSS software. RESULTS: A total of 137 patients underwent total thyroidectomy with prophylactic ipsilateral central and level 3 dissection for PTC. The incidence of occult level 3 disease was 30 % (41/137 patients). A total of 48 % of patients (66/137) harbored occult central neck disease. A total of 80.5 % of patients with pN1b disease had macrometastases (>=2 mm), and 15 % exhibited skip metastases with central compartment sparing. In patients with pN1b disease, a median of 6 level 3 nodes were retrieved, with an average involved nodal ratio of 0.29. Multivariate regression demonstrated risk factors for occult lateral neck metastasis include tumor size (odds ratio 1.1), upper pole tumors (odds ratio 6.6), and vascular invasion (odds ratio 3.2) (p < 0.05). CONCLUSIONS: PTC is associated with a significant incidence of occult central and lateral nodal metastases. In patients undergoing prophylactic central neck dissection, inclusion of level 3 dissection should be considered in patients with large upper lobe cancers. PMID- 27188297 TI - Value of Percutaneous Radiologic Gastrostomy for Patients with Advanced Esophageal Cancer. AB - BACKGROUND: Nutritional management is important throughout the treatment period for esophageal cancer patients. This study aimed to evaluate the feasibility of percutaneous radiologic gastrostomy (PRG) and to investigate whether PRG can be applied for patients with advanced esophageal cancer. METHODS: In this study, 89 patients (74 men and 15 women) with advanced esophageal cancer underwent PRG using computed tomography and fluoroscopic guidance. These patients were unsuitable candidates for endoscopic intervention because of esophageal stricture. Primary placement of a mushroom-retained gastrostomy catheter was intended. The end points were technical success and complications after PRG as well as clinical outcomes and survival of the patients. These end points also were compared between the pre-chemoradiotherapy (pre-CRT) and post-CRT groups using the Chi square test, Fisher's exact test, and the Wilcoxon rank sum test. The survival rate was calculated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: All the patients had a successful PRG. The mushroom tip gastrostomy catheter was primarily inserted in 77 patients (86.5 %) and finally achieved for all the patients. Complications occurred for 14 patients (15.7 %) including Dindo-Clavien classification grade 3 (1 catheter dislodgement), grade 2 (2 gastric hemorrhages), and grade 1 (7 skin infections and 4 oozing hemorrhages) complications. During the follow-up period (median, 6 months), 60 patients (67.4 %) died, giving a 12-month survival rate of 37.7 %. Gastrostomy removal was more common in the pre-CRT group (P = 0.011). The pre-CRT group had higher survival rates than the post-CRT group (P = 0.021). CONCLUSIONS: Because PRG provided high technical success with limited complications, it can be used for patients with advanced esophageal cancer whose treatment plan involves multimodal therapy. PMID- 27188298 TI - The History of the HIV/AIDS Epidemic in Africa. AB - HIV testing of African immigrants in Belgium showed that HIV existed among Africans by 1983. However, the epidemic was recognized much later in most parts of sub-Saharan Africa (SSA) due to stigma and perceived fear of possible negative consequences to the countries' economies. This delay had devastating mortality, morbidity, and social consequences. In countries where earlier recognition occurred, political leadership was vital in mounting a response. The response involved establishment of AIDS control programs and research on the HIV epidemiology and candidate preventive interventions. Over time, the number of effective interventions has grown; the game changer being triple antiretroviral therapy (ART). ART has led to a rapid decline in HIV-related morbidity and mortality in addition to prevention of onward HIV transmission. Other effective interventions include safe male circumcision, pre-exposure prophylaxis, and post exposure prophylaxis. However, since none of these is sufficient by itself, delivering a combination package of these interventions is important for ending the HIV epidemic as a public health threat. PMID- 27188299 TI - Cognitive Impairment and Persistent CNS Injury in Treated HIV. AB - The implementation of combination antiretroviral therapy (cART) has changed HIV infection into a chronic illness, conveying extensive benefits, including greater longevity and advantages for the central nervous system (CNS). However, studies increasingly confirm that the CNS gains are incomplete, with reports of persistent immune activation affecting the CNS despite suppression of plasma HIV RNA. The rate of cognitive impairment is unchanged, although severity is generally milder than in the pre-cART era. In this review, we discuss cognitive outcomes from recently published clinical HIV studies, review observations on HIV biomarkers for cognitive change, and emphasize longitudinal imaging findings. Additionally, we summarize recent studies on CNS viral invasion, CD8 encephalitis, and how CNS involvement during the earliest stages of infection may set the stage for later cognitive manifestations. PMID- 27188300 TI - Understanding Sustained Retention in HIV/AIDS Care and Treatment: a Synthetic Review. AB - Sustained retention represents an enduring and evolving challenge to HIV treatment programs in Africa. We present a theoretical framework for sustained retention borrowing from ecologic principles of sustainability and dynamic adaptation. We posit that sustained retention from the patient perspective is dependent on three foundational principles: (1) patient activation: the acceptance, prioritization, literacy, and skills to manage a chronic disease condition, (2) social normalization: the engagement of a social network and harnessing social capital to support care and treatment, and (3) livelihood routinization: the integration of care and treatment activities into livelihood priorities that may change over time. Using this framework, we highlight barriers specific to sustained retention and review interventions addressing long-term, sustained retention in HIV care with a focus on Sub-Saharan Africa. PMID- 27188301 TI - What questions can a placebo answer? AB - The concept of clinical equipoise restricts the use of placebo controls in clinical trials when there already exists a proven effective treatment. Several critics of clinical equipoise have put forward alleged counter-examples to this restriction-describing instances of ethical placebo-controlled trials that apparently violate clinical equipoise. In this essay, we respond to these examples and show that clinical equipoise is not as restrictive of placebos as these authors assume. We argue that a subtler appreciation for clinical equipoise in particular the distinction between de facto and de jure interpretations of the concept-allows the concept to explain when and why a placebo control may be necessary to answer a question of clinical importance. PMID- 27188303 TI - Site selection for installing plasma incinerator reactor using the GIS in Rudsar county, Iran. AB - Nowadays, the urban waste disposal and the proper location for doing so is considered as one of the most important urban service issues, which has the potential of causing environmental hazards for the citizens, if not done properly. One of the newest methods of waste burial is using plasma incinerator reactors. Using the advanced technology of plasma reactors in waste disposal has been the subject of study for a considerable number of researchers in the last few years. Moreover, insignificant emissions of environmental pollutants and high efficiency in these reactors have led to a high incentive for using them in the area of urban services. Therefore, finding the proper location for the plasma incinerator reactor in order to minimize environmental hazards is considered as a very important issue. In the present study, different parts of this reactor and its working procedure are presented at first. Then, quantitative and qualitative criteria effective on locating plasma incinerator reactor are presented, and these criteria are given proper weights using analytic hierarchy process (AHP) multi-criteria decision making method. Next, the data were collected for the studying area, and then, weighting, analysis, and presentation of geospatial data were performed using the geographic information system (GIS). Finally, the output map for installing location of the plasma incinerator reactor was developed in three classes of good, average, and bad. PMID- 27188302 TI - Heavy metal pollution in sediments and mussels: assessment by using pollution indices and metallothionein levels. AB - In the present work, the concentration of eight metals (Cd, Cr, Cu, Fe, Mn, Ni, Pb, Zn) was determined in the sediments and transplanted and native mussels (Mytilus galloprovincialis). The study was conducted in Turkish marinas, shipyards, and shipbreaking yards. The effect of metal pollution was evaluated by determining the levels of metallothionein (MT) in the mussels. The extent of contamination for each single metal was assessed by using the geoaccumulation index (I geo) and enrichment factor (EF). Whereas, to evaluate the overall metal pollution and effect, the pollution load index (PLI), modified contamination degree (mC d), potential toxicity response index (RI), mean effects range median (ERM) quotient (m-ERM-Q), and mean PEL quotient (m-PEL-Q) were calculated. The influence of different background values on the calculations was discussed. The results indicated a significant metal pollution caused by Cu, Pb, and Zn especially in shipyard and shipbreaking sites. Higher concentrations of MT were observed in the ship/breaking yard samples after the transplantation. PMID- 27188304 TI - A biologically inspired attachable, self-standing nanofibrous membrane for versatile use in oil-water separation. AB - Uloborus walckenaerius spider webs provided the inspiration for attachable, self standing nanofibre sheets. The developed product adds selective wettability against oil-water mixtures to both 2D and 3D materials by attaching or covering them, leading to successful separation through a facile, scalable and low-cost process. PMID- 27188307 TI - Stillbirths and neonatal deaths vary significantly across UK, figures show. PMID- 27188305 TI - Which health research gets used and why? An empirical analysis of 30 cases. AB - BACKGROUND: While health research is considered essential for improving health worldwide, it remains unclear how it is best organized to contribute to health. This study examined research that was part of a Ghanaian-Dutch research program that aimed to increase the likelihood that results would be used by funding research that focused on national research priorities and was led by local researchers. The aim of this study was to map the contribution of this research to action and examine which features of research and translation processes were associated with the use of the results. METHODS: Using Contribution Mapping, we systematically examined how 30 studies evolved and how results were used to contribute to action. We combined interviews with 113 purposively selected key informants, document analysis and triangulation to map how research and translation processes evolved and contributions to action were realized. After each case was analysed separately, a cross-case analysis was conducted to identify patterns in the association between features of research processes and the use of research. RESULTS: The results of 20 of the 30 studies were used to contribute to action within 12 months. The priority setting and proposal selection process led to the funding of studies which were from the outset closely aligned with health sector priorities. Research was most likely to be used when it was initiated and conducted by people who were in a position to use their results in their own work. The results of 17 out of 18 of these user initiated studies were translated into action. Other features of research that appeared to contribute to its use were involving potential key users in formulating proposals and developing recommendations. CONCLUSIONS: Our study underlines the importance of supporting research that meets locally-expressed needs and that is led by people embedded in the contexts in which results can be used. Supporting the involvement of health sector professionals in the design, conduct and interpretation of research appears to be an especially worthwhile investment. PMID- 27188306 TI - Taurine Reduced Epidural Fibrosis in Rat Models after Laminectomy via Downregulating EGR1. AB - BACKGROUND/AIMS: Epidural fibrosis, a common complication after laminectomy, has been demonstrated to be closely associated with poor surgical outcomes. Previous studies showed that taurine had remarkable anti-fibrotic effects on lung and liver fibrosis. We performed this study to investigate the effects of taurine in rat models of epidural fibrosis after laminectomy and to explore the potential molecular mechanism. METHODS: Laminectomy was performed on each rat to establish epidural fibrosis model. After taurine treatment, Masson's trichrome and immunohistochemistry staining were used to examine epidural fibrosis. Cell viability was determined using the Cell Counting Kit-8 assay. Annexin V/Propidium Iodide double staining was performed to detect fibroblasts apoptosis. Microarray was adopted to identify significantly changed mRNAs. mRNA expression was measured by qRT-PCR. Lentivirus infection was performed to establish stable knockdown and overexpression cell lines. The expression of fibrosis-related proteins was determined via Western blot. RESULTS: Taurine treatment markedly reduced laminectomy-induced epidural fibrosis in rat models. However, this effect of taurine was independent on TGF-beta/Smad pathway, evidenced by no change in the expression of TGF-beta and its receptors. Besides, taurine had almost no effect on cell apoptosis. Interestingly, taurine treatment significantly decreased expression of EGR1 (Early growth response protein 1), an enhancer of fibrosis, both in vivo and in vitro. Furthermore, overexpression of EGR1 increased activation of fibroblasts, while EGR1 knockdown achieved an opposite effect, indicating that EGR1 plays a key role in the inhibitory effect of taurine on TGF beta-induced fibrosis. CONCLUSIONS: Reduced epidural fibrosis in vivo and decreased activation of fibroblasts in vitro after taurine treatment was mediated by EGR1. Taurine promises to be a potential prevention for epidural fibrosis after laminectomy. PMID- 27188308 TI - A cholera outbreak in Alborz Province, Iran: a matched case-control study. AB - OBJECTIVES: A total of 229 confirmed cholera cases were reported in Alborz Province during an outbreak that lasted from June 2011 to August 2011. This study aimed to identify potential sources of transmission in order to determine suitable interventions in similar outbreaks. In other words, the lessons learned from this retrospective study can be utilized to manage future similar outbreaks. METHODS: An age-matched and sex-matched case-control study was conducted during the outbreak. For each case, two control subjects were selected from the neighborhood. A case of cholera was defined as a bacteriologically confirmed case with signs and symptoms of cholera. This study was conducted from June 14, 2011 through August 23, 2011. The data were analyzed by calculating odds ratios (ORs) using the logistic regression method. RESULTS: In this outbreak, 229 confirmed cholera cases were diagnosed. The following risk factors were found to be associated with cholera: consumption of unrefrigerated leftover food (OR, 3.05; 95% confidence interval [CI], 1.72 to 5.41), consumption of vegetables and fruits in the previous three days (OR, 2.75; 95% CI, 1.95 to 3.89), and a history of traveling in the previous five days (OR, 5.31; 95% CI, 2.21 to 9.72). CONCLUSIONS: Consumption of vegetables and fruits has remained an unresolved risk factor in cholera outbreaks in Iran in recent years. In order to reduce the risk of cholera, sanitary standards for fruits and vegetables should be observed at all points from production to consumption, the population should be educated regarding hygienic food storage during outbreaks, and sanitary standards should be maintained when traveling during cholera outbreaks. PMID- 27188310 TI - Hypertransaminasemia and hypophosphoremia in an adolescent with anorexia nervosa: an event to watch for. AB - BACKGROUND: Anorexia Nervosa is a Psychiatric eating disorder of adolescence age with a high morbidity and mortality. CASE PRESENTATION: We describe a common case of anorexia nervosa (AN) in a female adolescent complicated by less known conditions related to refeeding syndrome. At admission, the girl showed a mild hypercholesterolemia with progressive normalization of the values. The initial low hypertransaminasemia worsened after refeeding until very high levels and hypophosphoremia was also described. Only a controlled caloric intake and a specific electrolyte supplementation led to the improvement of hematologic values and the clinical condition of the patient. CONCLUSIONS: Refeeding complications must be always suspected because of life-threatening risk. More attention should be paid not only to the acute state of the disease but also to the prevention and the management of refeeding-related manifestations. PMID- 27188309 TI - Risk factors for heart failure in a cohort of patients with newly diagnosed myocardial infarction: a matched, case-control study in Iran. AB - OBJECTIVES: Risk factors for heart failure (HF) have not yet been studied in myocardial infarction (MI) patients in Iran. This study was conducted to determine these risk factors. METHODS: In this nationwide, hospital-based, case control study, the participants were all new MI patients hospitalized from April 2012 to March 2013 in Iran. The data on 1,691 new cases with HF (enrolled by census sampling) were compared with the data of 6,764 patients without HF as controls. We randomly selected four controls per one case, matched on the date at MI and HF diagnosis, according to incidence density sampling. Using conditional logistic regression models, odds ratios (ORs) with a 95% confidence interval (CI) were calculated to identify potential risk factors. RESULTS: The one-year in hospital mortality rate was 18.2% in the cases and higher than in the controls (12.1%) (p<0.05). Significant risk factors for HF were: right bundle branch block (RBBB) (OR, 2.86; 95% CI, 1.95 to 4.19), stroke (OR, 2.00; 95% CI, 1.39 to 2.89), and coronary artery bypass grafting (CABG) (OR, 2.03; 95% CI, 1.34 to 3.09). Diabetes, hypertension, percutaneous coronary intervention (PCI), atrial fibrillation, ventricular tachycardia, and age were determined to be the factors significantly associated with HF incidence (p<0.05). The most important factor in women was diabetes (OR, 1.41; 95% CI, 1.05 to 1.88). Age, hypertension, PCI, CABG, and RBBB were the most important factors in men. CONCLUSIONS: Our findings may help to better identify and monitor the predictive risk factors for HF in MI patients. The pattern of risk factors was different in men and women. PMID- 27188312 TI - Present and foreseeable future of metabolomics in forensic analysis. AB - The revulsive publications during the last years on the precariousness of forensic sciences worldwide have promoted the move of major steps towards improvement of this science. One of the steps (viz. a higher involvement of metabolomics in the new era of forensic analysis) deserves to be discussed under different angles. Thus, the characteristics of metabolomics that make it a useful tool in forensic analysis, the aspects in which this omics is so far implicit, but not mentioned in forensic analyses, and how typical forensic parameters such as the post-mortem interval or fingerprints take benefits from metabolomics are critically discussed in this review. The way in which the metabolomics-forensic binomial succeeds when either conventional or less frequent samples are used is highlighted here. Finally, the pillars that should support future developments involving metabolomics and forensic analysis, and the research required for a fruitful in-depth involvement of metabolomics in forensic analysis are critically discussed. PMID- 27188311 TI - A comprehensive database of high-throughput sequencing-based RNA secondary structure probing data (Structure Surfer). AB - BACKGROUND: RNA molecules fold into complex three-dimensional shapes, guided by the pattern of hydrogen bonding between nucleotides. This pattern of base pairing, known as RNA secondary structure, is critical to their cellular function. Recently several diverse methods have been developed to assay RNA secondary structure on a transcriptome-wide scale using high-throughput sequencing. Each approach has its own strengths and caveats, however there is no widely available tool for visualizing and comparing the results from these varied methods. METHODS: To address this, we have developed Structure Surfer, a database and visualization tool for inspecting RNA secondary structure in six transcriptome-wide data sets from human and mouse ( http://tesla.pcbi.upenn.edu/strucuturesurfer/ ). The data sets were generated using four different high-throughput sequencing based methods. Each one was analyzed with a scoring pipeline specific to its experimental design. Users of Structure Surfer have the ability to query individual loci as well as detect trends across multiple sites. RESULTS: Here, we describe the included data sets and their differences. We illustrate the database's function by examining known structural elements and we explore example use cases in which combined data is used to detect structural trends. CONCLUSIONS: In total, Structure Surfer provides an easy-to-use database and visualization interface for allowing users to interrogate the currently available transcriptome-wide RNA secondary structure information for mammals. PMID- 27188313 TI - High and low frequency unfolded partial least squares regression based on empirical mode decomposition for quantitative analysis of fuel oil samples. AB - Accurate prediction of the model is fundamental to the successful analysis of complex samples. To utilize abundant information embedded over frequency and time domains, a novel regression model is presented for quantitative analysis of hydrocarbon contents in the fuel oil samples. The proposed method named as high and low frequency unfolded PLSR (HLUPLSR), which integrates empirical mode decomposition (EMD) and unfolded strategy with partial least squares regression (PLSR). In the proposed method, the original signals are firstly decomposed into a finite number of intrinsic mode functions (IMFs) and a residue by EMD. Secondly, the former high frequency IMFs are summed as a high frequency matrix and the latter IMFs and residue are summed as a low frequency matrix. Finally, the two matrices are unfolded to an extended matrix in variable dimension, and then the PLSR model is built between the extended matrix and the target values. Coupled with Ultraviolet (UV) spectroscopy, HLUPLSR has been applied to determine hydrocarbon contents of light gas oil and diesel fuels samples. Comparing with single PLSR and other signal processing techniques, the proposed method shows superiority in prediction ability and better model interpretation. Therefore, HLUPLSR method provides a promising tool for quantitative analysis of complex samples. PMID- 27188314 TI - Analysis of diacylglycerols by ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry: Double bond location and isomers separation. AB - Diacylglycerols (DAGs) are important lipid intermediates and have been implicated in human diseases. Isomerism complicates their mass spectrometric analysis; in particular, it is difficult to identify fatty acid substituents and locate the double bond positions in unsaturated DAGs. We have developed an analytical strategy using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) in conjunction with dimethyl disulfide (DMDS) derivatization and collision cross-section (CCS) measurement to characterize DAGs in biological samples. The method employs non-aqueous reversed-phase chromatographic separation and profile collision energy (CE) mode for MS(E) and MS/MS analyses. Three types of fragment ions were produced simultaneously. Hydrocarbon ions (m/z 50-200) obtained at high CE helped to distinguish unsaturated and saturated DAGs rapidly. Neutral loss ions and acylium ions (m/z 300-400) produced at low CE were used to identify fatty acid substituents. Informative methyl thioalkane fragment ions were used to locate the double bonds of unsaturated DAGs. Mono-methylthio derivatives were formed mainly by the reaction of DAGs with DMDS, where methyl thiol underwent addition to the first double bond farthest from the ester terminus of unsaturated fatty acid chains. The addition of CCS values maximized the separation of isomeric DAG species and improved the confidence of DAG identification. Fourteen DAGs were identified in mouse myotube cells based on accurate masses, characteristic fragment ions, DMDS derivatization, and CCS values. PMID- 27188315 TI - Alterations of the exo- and endometabolite profiles in breast cancer cell lines: A mass spectrometry-based metabolomics approach. AB - In recent years, knowledge about metabolite changes which are characteristic for the physiologic state of cancer cells has been acquired by liquid chromatography coupled to mass spectrometry. Distinct molecularly characterized breast cancer cell lines provide an unbiased and standardized in vitro tumor model reflecting the heterogeneity of the disease. Tandem mass spectrometry is a widely applied analytical platform and highly sensitive technique for analysis of complex biological samples. Endo- and exometabolite analysis of the breast cancer cell lines MDA-MB-231, -453 and BT-474 as well as the breast epithelial cell line MCF 10A has been performed using two different analytical platforms: UPLC-ESI-Q-TOF based on a scheduled precursor list has been applied for highlighting of significant differences between cell lines and HPLC-ESI-QqQ using multiple reaction monitoring has been utilized for a targeted approach focusing on RNA metabolism and interconnected pathways, respectively. Statistical analysis enabled a clear discrimination of the breast epithelial from the breast cancer cell lines. As an effect of oxidative stress, a decreased GSH/GSSG ratio has been detected in breast cancer cell lines. The triple negative breast cancer cell line MDA-MB-231 showed an elevation in nicotinamide, 1-ribosyl-nicotinamide and NAD+ reflecting the increased energy demand in triple negative breast cancer, which has a more aggressive clinical course than other forms of breast cancer. Obtained distinct metabolite pattern could be correlated with distinct molecular characteristics of breast cancer cells. Results and methodology of this preliminary in vitro study could be transferred to in vivo studies with breast cancer patients. PMID- 27188316 TI - Liquid chromatography-tandem mass spectrometry analysis of neonicotinoid pesticides and 6-chloronicotinic acid in environmental water with direct aqueous injection. AB - An efficient, high throughput and cost-effective direct aqueous injection approach for the analysis of neonicotinoid pesticides and a common metabolite in environmental water has been described here. The method determines eight neonicotinoid pesticides (acetamiprid, clothianidin, dinotefuran, flonicamid, imidacloprid, nitenpyram, thiacloprid, thiamethoxam) and 6-chloronicotinic acid (a common metabolite of the first generation neonicotinoids, acetamiprid, imidacloprid, nitenpyram and thiacloprid) without any sample enrichment/cleanup steps. The method detection limits are 2-8 ng/L for the neonicotinoids and 93 ng/L for 6-chloronicotinic acid. The performance of the QTRAP((r))5500 mass spectrometer was compared against a 4000QTRAP((r)), and a QTRAP((r))6500, to provide insights for future method transfer among different generations of instrumentations. Critical mass spectrometric parameters such as collision energy were quite consistent among the three instruments evaluated. However, increased chemical background levels for some target compounds on the more sensitive instruments were observed. The application of differential ion mobility spectrometry combined with tandem mass spectrometry was demonstrated to have great potential in reducing chemical background and/or isobaric interferences inherited in sample matrices. This ISO 17025 accredited method was employed to quantitate neonicotinoids in Ontario stream water samples. Good correlation for analytical results of this direct aqueous injection approach and a previously published solid phase extraction approach warrant high confidence in data quality. PMID- 27188318 TI - Glass substrates crosslinked with tetracycline-imprinted polymeric silicate and CdTe quantum dots as fluorescent sensors. AB - A fluorescence-based sensor that combines the merits of quantum dots (QDs) and molecularly imprinted polymers (MIPs) was first fabricated on a glass substrate via a sol-gel route. Some of the key performance factors, including silane selection, substrate etching, the reaction times of glass silanization and sol gel polymerization, and the times and methods used for template stripping and loading, were discussed and determined. After fabricating the sensor on either a 3-aminopropyltriethoxysilane (APS) or a 3-mercaptopropyltriethoxysilane (MPS) modified glass substrate, APS showed a much better performance than MPS as both the capping reagent of QDs and the functional monomer of tetracycline-templated MIPs. The APS-QDs on APS-modified glass had a higher imprinted factor (IF = 5.6), a lower LOD (2.1 MUM, 3sigma), and a more stable signal (2.8%, n = 10 at 70 MUM) than those on the MPS-modified glass (IF = 5.2, LOD = 6.5 MUM, stability = 6.2%). Furthermore, the recoveries of tetracycline (70 MUM) from BSA (133 MUg/mL) and FBS (0.66 ppt) by the APS-modified glass were 98% (RSD = 3.5%, n = 5) and 97% (RSD = 5.7%), respectively. For the MPS-modified glass, recoveries of 95% (RSD = 7.2%) and 89% (RSD = 8.7%) were observed at 67 MUg/mL of BSA and 0.33 ppt of FBS, respectively. PMID- 27188317 TI - Graphene-polyaniline modified electrochemical droplet-based microfluidic sensor for high-throughput determination of 4-aminophenol. AB - We report herein the first development of graphene-polyaniline modified carbon paste electrode (G-PANI/CPE) coupled with droplet-based microfluidic sensor for high-throughput detection of 4-aminophenol (4-AP) in pharmaceutical paracetamol (PA) formulations. A simple T-junction microfluidic platform using an oil flow rate of 1.8 MUL/min and an aqueous flow rate of 0.8 MUL/min was used to produce aqueous testing microdroplets continuously. The microchannel was designed to extend the aqueous droplet to cover all 3 electrodes, allowing for electrochemical measurements in a single droplet. Parameters including flow rate, water fraction, and applied detection potential (Edet) were investigated to obtain optimal conditions. Using G-PANI/CPE significantly increased the current response for both cyclic voltammetric detections of ferri/ferrocyanide [Fe(CN)6](3-/4-) (10 times) and 4-AP (2 times), compared to an unmodified electrode. Using the optimized conditions in the droplet system, 4-AP in the presence of PA was selectively determined. The linear range of 4-AP was 50-500 MUM (R(2) = 0.99), limit of detection (LOD, S/N = 3) was 15.68 MUM, and limit of quantification (LOQ, S/N = 10) was 52.28 MUM. Finally, the system was used to determine 4-AP spiked in commercial PA liquid samples and the amounts of 4-AP were found in good agreement with those obtained from the conventional capillary zone electrophoresis/UV-Visible spectrophotometry (CZE/UV-Vis). The proposed microfluidic device could be employed for a high-throughput screening (at least 60 samples h(-1)) of pharmaceutical purity requiring low sample and reagent consumption. PMID- 27188319 TI - Fabrication of interdigitated high-performance zinc oxide nanowire modified electrodes for glucose sensing. AB - Diabetes is a metabolic disease with a prolonged elevated level of glucose in the blood leads to long-term complications and increases the chances for cardiovascular diseases. The present study describes the fabrication of a ZnO nanowire (NW)-modified interdigitated electrode (IDE) to monitor the level of blood glucose. A silver IDE was generated by wet etching-assisted conventional lithography, with a gap between adjacent electrodes of 98.80 MUm. The ZnO-based thin films and NWs were amended by sol-gel and hydrothermal routes. High-quality crystalline and c-axis orientated ZnO thin films were observed by XRD analyses. The ZnO thin film was annealed for 1, 3 and 5 h, yielding a good-quality crystallite with sizes of 50, 100 and 110 nm, and the band gaps were measured as 3.26, 3.20 and 3.17 eV, respectively. Furthermore, a flower-modeled NW was obtained with the lowest diameter of 21 nm. Our designed ZnO NW-modified IDE was shown to have a detection limit as low as 0.03 mg/dL (correlation coefficient = 0.98952) of glucose with a low response time of 3 s, perform better than commercial glucose meter, suitable to instantly monitor the glucose level of diabetes patients. This study demonstrated the high performance of NW-mediated IDEs for glucose sensing as alternative to current glucose sensors. PMID- 27188320 TI - Upconverting nanophosphors as reporters in a highly sensitive heterogeneous immunoassay for cardiac troponin I. AB - Photon upconverting nanophosphors (UCNPs) have a unique capability to produce anti-Stokes emission at visible wavelengths via sequential multiphoton absorption upon infrared excitation. Since the anti-Stokes emission can be easily spectrally resolved from the Stokes' shifted autofluorescence, the upconversion luminescence (UCL) is a highly attractive reporter technology for optical biosensors and biomolecular binding assays - potentially enabling unprecedented sensitivity in separation-based solid-phase immunoassays. UCL technology has not previously been applied in sensitive detection of cardiac troponin I (cTnI), which requires highly sensitive detection to enable accurate and timely diagnosis of myocardial infarction. We have developed an UCL-based immunoassay for cTnI using NaYF4: Yb(3+), Er(3+) UCNPs as reporters. Biotinylated anti-cTnI monoclonal antibody (Mab) and Fab fragment immobilized to streptavidin-coated wells were used to capture cTnI. Captured cTnI was detected from dry well surface after a 15 min incubation with poly(acrylic acid) coated UCNPs conjugated to second anti-cTnI Mab. UCL was measured with a dedicated UCL microplate reader. The UCL-based immunoassay allowed sensitive detection of cTnI. The limit of detection was 3.14 ng L(-1). The calibration curve was linear up to cTnI concentration 50,000 ng L( 1). Plasma recoveries of added cTnI were 92-117%. Obtained cTnI concentrations from five normal plasma samples were 4.13-10.7 ng L(-1) (median 5.06 ng L(-1)). There is yet significant potential for even further improved limit of detection by reducing non-specifically bound fraction of the Mab-conjugated UCNPs. The assay background with zero calibrator was over 40-fold compared to the background obtained from wells where the reporter conjugate had been excluded. PMID- 27188321 TI - Rapid "one-pot" preparation of polymeric monolith via photo-initiated thiol acrylate polymerization for capillary liquid chromatography. AB - A facile approach was exploited for fast preparation of polymer-based monoliths in UV-transparent fused-silica capillaries via "one-pot" photo-initiated thiol acrylate polymerization reaction of dipentaerythritolpenta-/hexaacrylate (DPEPA) and 1-octadecanethiol (ODT) in the presence of porogenic solvents (1-butanol and ethylene glycol). Due to relative insensitivity of oxygen inhibition in thiol-ene free-radical polymerization, the polymerization could be performed within 5 min. The effects of composition of prepolymerization solution on the morphology and permeability of poly(ODT-co-DPEPA) monoliths were investigated in detail by adjusting the content of monomer and binary porogen ratio. The physical properties of poly(ODT-co-DPEPA) monoliths were characterized by Fourier transform infrared spectroscopy (FT-IR), mercury intrusion porosimetry (MIP) and nitrogen adsorption/desorption measurement. The evaluation of chromatographic performance was carried out by capillary liquid chromatography (cLC). The results indicated that the poly(ODT-co-DPEPA) monolith was homogeneous and permeable, and also possessed a typical reversed-phase retention mechanism in cLC with high efficiency (~75,000 N m(-1)) for separation of alkylbenzenes. Eventually, the further separation of tryptic digest of proteins by cLC tandem mass spectrometry (cLC-MS/MS) demonstrated its potential in the analysis of biological samples. PMID- 27188322 TI - Blood-brain barrier shuttle peptides: an emerging paradigm for brain delivery. AB - Brain delivery is one of the major challenges in drug development because of the high number of patients suffering from neural diseases and the low efficiency of the treatments available. Although the blood-brain barrier (BBB) prevents most drugs from reaching their targets, molecular vectors - known as BBB shuttles - offer great promise to safely overcome this formidable obstacle. In recent years, peptide shuttles have received growing attention because of their lower cost, reduced immunogenicity, and higher chemical versatility than traditional Trojan horse antibodies and other proteins. PMID- 27188323 TI - Achieving high resolution and optimizing sensitivity in spatial frequency encoding NMR spectroscopy: from theory to practice. AB - A detailed analysis of NMR spectra acquired based on spatial frequency encoding is presented. A theoretical model to simulate gradient encoded pulses is developed in order to describe the spatial properties of the NMR signals that are locally created throughout the sample. The key features that affect the efficiency of the slice selection process during excitation as well as refocusing pulses are investigated on a model ABX spin system, both theoretically and experimentally. It is shown that the sensitivity and resolution of the pure shift and J-edited experiments based on a spatial frequency encoding can be optimized to a point where high-resolution techniques based on a spatial frequency encoding approach show optimal performance compared to other methods. PMID- 27188324 TI - Migrants' right to healthcare: accepting limits on what European healthcare systems can provide. PMID- 27188325 TI - Sensing hydrocarbons with interband cascade lasers and substrate-integrated hollow waveguides. AB - Tunable diode laser absorption spectroscopy (TDLAS) is an excellent analytical technique for gas sensing applications. In situ sensing of relevant hydrocarbon gases is of substantial interest for a variety of in-field scenarios including environmental monitoring and process analysis, ideally providing accurate, molecule specific, and rapid information with minimal sampling requirements. Substrate-integrated hollow waveguides (iHWGs) have demonstrated superior properties for gas sensing applications owing to minimal sample volumes required while simultaneously serving as efficient photon conduits. Interband cascade lasers (ICLs) are recently emerging as mid-infrared light sources operating at room temperature, with low power consumption, and providing excellent potential for integration. Thereby, portable and handheld mid-infrared sensing devices are facilitated. Methane (CH4) is among the most frequently occurring, and thus, highly relevant hydrocarbons requiring in situ emission monitoring by taking advantage of its distinct molecular absorption around 3 MUm. Here, an efficient combination of iHWGs with ICLs is presented providing a methane sensor calibrated in the range of 100 to 2000 ppmv with a limit of detection at 38 ppmv at the current stage of development. Furthermore, a measurement precision of 0.62 ppbv during only 1 s of averaging time has been demonstrated, thereby rendering this sensor concept useful for in-line and on-site emission monitoring and process control applications. PMID- 27188326 TI - Coincidental cerebral venous thrombosis and subarachnoid haemorrhage related to ruptured anterior communicating artery aneurysm. AB - Aneurysmal subarachnoid haemorrhage (SAH) and cerebral venous thrombosis (CVT) are rare cerebrovascular pathologies. Here, we report the extremely rare coincidental presentation of both entities and discuss the likely relationship in aetiology and their optimal management. A female patient presented with headache and progressive neurological deficits. Cranial computed tomography and contrast enhanced magnetic resonance imaging (MRI)/magnetic resonance angiography (MRA) revealed dural venous sinus thrombosis, left-sided frontal and parietal infarcts, and left middle and anterior cerebral artery stenosis. In addition, left hemispheric subarachnoid haemosiderosis was seen on MRI. Following standard anticoagulation therapy for CVT, she represented with acute SAH. Digital subtraction angiography revealed a ruptured anterior communicating artery aneurysm and left middle cerebral artery/anterior cerebral artery vasospasms that were responsive to intra-arterial nimodipine. The latter were already present on the previous MRI, and had most likely prevented the detection of the aneurysm initially. The aneurysm was successfully coil embolised, and the patient improved clinically. Despite this case being an extremely rare coincidence, a ruptured aneurysm should be excluded in the presence of CVT and non-sulcal SAH. A careful consideration of treatment of both pathologies is required, since anticoagulation may have a potentially negative impact on aneurysmal bleeding. PMID- 27188328 TI - Axial spondyloarthritis. AB - The term axial spondyloarthritis covers both non-radiographic disease and radiographic disease (also known as ankylosing spondylitis). Some studies have been performed to investigate the prevalence of axial spondyloarthritis, although most are limited to patients with radiographic disease. A strong genetic association has been shown between axial spondyloarthritis and human leukocyte antigen-B27 (HLA-B27), but the pathogenetic role of HLA-B27 has not yet been clarified. Tumour necrosis factor (TNF), IL-17, IL-23 and downstream pathways also seem to be important - based on the good results of therapies directed against these molecules - but their exact role in the inflammatory process is also not yet clear. Elucidating the interaction between osteoproliferation and inflammation will be crucial for the prevention of long-term structural damage of the bone. The development of new criteria for classification, diagnosis and screening of patients with axial spondyloarthritis will enable earlier intervention for this chronic inflammatory disease. MRI has become an important tool for the early detection of axial spondyloarthritis. NSAIDs and TNF blockers are effective therapies, including in the early non-radiographic stage. Therapeutic blockade of IL-17 or IL-23 seems to be a promising new treatment option. Tools for measuring quality of life in axial spondyloarthritis have become relevant to assess the impact that the disease has on patients. These diagnostic and therapeutic advances will continue to change the management of axial spondyloarthritis, and new insights into the disease pathogenesis will hopefully accelerate this process. For an illustrated summary of this Primer, visit: http://go.nature.com/51b1af. PMID- 27188327 TI - Characterization of a murine xenograft model for contrast agent development in breast lesion malignancy assessment. AB - BACKGROUND: The aim of the study was to develop a nude mouse xenograft model implanted with both benign and malignant xenografts as the preliminary candidate screening tool for contrast agent development in lesion malignancy indication. RESULTS: A malignant xenograft (either MCF-7 cell/matrigelTM or MDA-MB 231 cell/matrigel) and a benign xenograft (culture medium/matrigel) with cleft and slit-like features of intracanaliculer fibroadenoma were implanted subcutaneously into flanks of individual nu/nu nude mouse with >90 % successful inoculation rate. Both malignant and benign xenografts with volume up to 4 cm(3) and (size up to 2 cm) after 5(th) week were characterized in vivo by sonogram (exhibiting endogenous morphological contrast features between benign and malignant xenografts), dynamic contrast enhanced multi-detector computed tomography (presenting non-targeting exogenous morphological and dynamic contrast features between benign and malignant xenografts), and then were harvested for histological and immunohistochemistry (revealing example of targeting/molecular contrast features, such as expression of cancer vascular markers of malignant xenografts). Malignant xenografts appeared morphologically taller than wide (axis parallel to skin) with angular/ill-defined margin under sonogram observations, revealed more evident rim enhancement, angular margin and washout pattern in the time-density curve from dynamic contrast enhance multi-detector computed tomography images, and had more visible cancer vascular markers (CD31 and VEGF) expression. With limited number of subjects (5-27 for each group of a specific imaging contrast feature), those imaging contrast features of the xenograft model had larger than 85 % sensitivity, specificity, accuracy, positive and negative prediction values in indicating xenograft malignancy except for results from color Doppler detections. CONCLUSIONS: The murine xenograft model might provide an earlier efficacy evaluation of new contrast agent candidate for lesion malignancy interrogation with qualitative and quantitative indication before a human study to reduce the risk and conserve the resources (time, finance and manpower). PMID- 27188330 TI - Erratum to: Quantifying the health impacts of ambient air pollutants: methodological errors must be avoided. PMID- 27188329 TI - Differential response of serum amyloid A to different therapies in early rheumatoid arthritis and its potential value as a disease activity biomarker. AB - BACKGROUND: The aim was to compare the effect of etanercept (ETN) and conventional synthetic disease-modifying anti-rheumatic drug (DMARD) therapy on serum amyloid A (SAA) levels and to determine whether SAA reflects rheumatoid arthritis (RA) disease activity better than C-reactive protein (CRP). METHODS: We measured SAA and CRP at baseline, 24, 48, and 102 week follow-up visits in 594 patients participating in the Treatment of early RA (TEAR) study. We used Spearman correlation coefficients (rho) to evaluate the relationship between SAA and CRP and mixed effects models to determine whether ETN and methotrexate (MTX) treatment compared to triple DMARD therapy differentially lowered SAA. Akaike information criteria (AIC) were used to determine model fits. RESULTS: SAA levels were only moderately correlated with CRP levels (rho = 0.58, p < 0.0001). There were significant differences in SAA by both visit (p = 0.0197) and treatment arm (p = 0.0130). RA patients treated with ETN plus MTX had a larger reduction in SAA than patients treated with traditional DMARD therapy. Similar results were found for serum CRP by visit (p = 0.0254) and by treatment (p < 0.0001), with a more pronounced difference than for SAA. Across all patients and time points, models of the disease activity score of 28 joints (DAS28)-erythrocyte sedimentation rate (ESR) using SAA levels were better than models using CRP; the DeltaAIC between the SAA and CRP models was 305. CONCLUSIONS: SAA may be a better biomarker of RA disease activity than CRP, especially during treatment with tumor necrosis factor (TNF) antagonists. This warrants additional studies in other cohorts of patients on treatment for RA. TRIAL REGISTRATION: (ClinicalTrials.gov identifier: NCT00259610 , Date of registration: 28 November 2005). PMID- 27188332 TI - A cross-sectional study of submacular thickening in intermediate uveitis and determination of treatment threshold. AB - BACKGROUND: The aim of this work is to refine understanding of anatomical and functional alterations in eyes with Intermediate Uveitis (IU), their natural history in mild cases not necessitating treatment and their response to treatment in severely affected eyes with macular edema. METHODS: 61 consecutive patients with IU presenting over a 6-year period were prospectively recruited into the study. Two subgroups of patients with IU were identified on the basis of the need or not for systemic cortico-steroid treatment. A group of healthy volunteers was identified for determining normal average central foveal thickness (CFT) values. Statistical comparisons were sought between patient sub-groups and with the group of normal volunteers for CFT and Best Corrected Visual Acuity (BCVA) at baseline and after 6 months. In a post hoc analysis, a cut-off value of CFT for systemic treatment initiation in IU was statistically identified and its sensitivity and specificity determined. RESULTS: A statistically significant difference in mean CFT at baseline was observed between patients under systemic treatment and untreated patients (p = 0.0005) as well as between untreated patients and healthy volunteers. (p < 0.001) After six months difference in CFT between the two patients subgroups was no longer significant (p = 0.699). BCVA was worse for patients under systemic treatment. No statistically significant difference could be identified between the subgroup of untreated patients and the group of healthy volunteers either at baseline or after 6 months. Correlation between LogMAR visual acuity and central retinal thickness at baseline was strong (r = 0.7436, p < 0.0001, Pearson's correlation coefficient). The cut-off value of CFT for initiating systemic treatment was determined at 215.5 MUm in a post hoc analysis (sensitivity 62.5 %, specificity 96.4 %). CONCLUSIONS: Subclinical retinal thickening of mildly inflamed eyes with IU can occur though bearing no functional clinical significance and spontaneously resolving within 6 months. A cut-off CFT value for treatment of macular edema in IU, in the presence of other relevant morphological features on Optical Coherence Tomography, seems to emerge from post hoc analysis of collected data demonstrating strong specificity and moderate sensitivity. PMID- 27188331 TI - Brain morphological changes in adolescent and adult patients with anorexia nervosa. AB - Gray matter (GM) and white matter (WM) volume loss occur in the brains of patients with acute anorexia nervosa (AN) and improve again upon weight restoration. Adolescence is an important time period for AN to begin. However, little is known about the differences between brain changes in adolescents vs adults. We used a meta-analysis and a qualitative review of all MRI studies regarding acute structural brain volume changes and their recovery in adolescents and adults with AN. 29 studies with 473 acute, 121 short-term weight-recovered and 255 long-term recovered patients with AN were included in the meta-analysis. In acute AN, GM and WM were reduced compared to healthy controls. Acute adolescent patients showed a significantly greater GM reduction than adults (-8.4 vs -3.1 %), the difference in WM (-4.0 vs -2.1 %) did not reach significance. Short-term weight-recovered patients showed a remaining GM deficit of 3.6 % and a non-significant WM reduction of 0.9 % with no age differences. Following 1.5-8 years of remission, GM and WM were no longer significantly reduced in adults (GM 0.4 %, WM -0.7 %); long-term studies for adolescents were scarce. The qualitative review showed that GM volume loss was correlated with cognitive deficits and three studies found GM regions, cerebellar deficits and WM to be predictive of outcome. GM and WM are strongly reduced in acute AN and even more pronounced in adolescence. Long-term recovery appears to be complete for adults while no conclusions can be drawn for adolescents, thus caution remains. PMID- 27188333 TI - When clinical care is like research: the need for review and consent. AB - The prevailing "segregated model" for understanding clinical research sharply separates it from clinical care and subjects it to extensive regulations and guidelines. This approach is based on the fact that clinical research relies on procedures and methods-research biopsies, blinding, randomization, fixed treatment protocols, placebos-that pose risks and burdens to participants in order to collect data that might benefit all patients. Reliance on these methods raises the potential for exploitation and unfairness, and thus points to the need for independent ethical review and more extensive informed consent. In contrast, it is widely assumed that clinical care does not raise these ethical concerns because it is designed to promote the best interests of individual patients. The segregation of clinical research from clinical care has been largely effective at protecting research participants. At the same time, this approach ignores the fact that several aspects of standard clinical care, such as clinician training and scheduling, also pose some risks and burdens to present patients for the benefit of all patients. We argue that recently proposed learning health care systems offer a way to address this concern, and better protect patients, by developing integrated review and consent procedures. Specifically, current approaches base the need for independent ethical review and more extensive informed consent on whether an activity is categorized as clinical research or clinical care. An ethically sounder approach, which could be incorporated into learning health care systems, would be to base the need for independent ethical review and more extensive informed consent on the extent to which an activity poses risks to present patients for the benefit of all patients. PMID- 27188334 TI - Velocity-dependent quantum phase slips in 1D atomic superfluids. AB - Quantum phase slips are the primary excitations in one-dimensional superfluids and superconductors at low temperatures but their existence in ultracold quantum gases has not been demonstrated yet. We now study experimentally the nucleation rate of phase slips in one-dimensional superfluids realized with ultracold quantum gases, flowing along a periodic potential. We observe a crossover between a regime of temperature-dependent dissipation at small velocity and interaction and a second regime of velocity-dependent dissipation at larger velocity and interaction. This behavior is consistent with the predicted crossover from thermally-assisted quantum phase slips to purely quantum phase slips. PMID- 27188335 TI - Intravenous administration of lidocaine directly acts on spinal dorsal horn and produces analgesic effect: An in vivo patch-clamp analysis. AB - Intravenous lidocaine administration produces an analgesic effect in various pain states, such as neuropathic and acute pain, although the underlying mechanisms remains unclear. Here, we hypothesized that intravenous lidocaine acts on spinal cord neurons and induces analgesia in acute pain. We therefore examined the action of intravenous lidocaine in the spinal cord using the in vivo patch-clamp technique. We first investigated the effects of intravenous lidocaine using behavioural measures in rats. We then performed in vivo patch-clamp recording from spinal substantia gelatinosa (SG) neurons. Intravenous lidocaine had a dose dependent analgesic effect on the withdrawal response to noxious mechanical stimuli. In the electrophysiological experiments, intravenous lidocaine inhibited the excitatory postsynaptic currents (EPSCs) evoked by noxious pinch stimuli. Intravenous lidocaine also decreased the frequency, but did not change the amplitude, of both spontaneous and miniature EPSCs. However, it did not affect inhibitory postsynaptic currents. Furthermore, intravenous lidocaine induced outward currents in SG neurons. Intravenous lidocaine inhibits glutamate release from presynaptic terminals in spinal SG neurons. Concomitantly, it hyperpolarizes postsynaptic neurons by shifting the membrane potential. This decrease in the excitability of spinal dorsal horn neurons may be a possible mechanism for the analgesic action of intravenous lidocaine in acute pain. PMID- 27188336 TI - Effects of intrauterine growth retardation and Bacillus subtilis PB6 supplementation on growth performance, intestinal development and immune function of piglets during the suckling period. AB - OBJECTIVES: The aim of this study was to investigate the effects of intrauterine growth retardation (IUGR) and Bacillus subtilis PB6 supplementation in formula milk (FORM) on growth performance, intestinal development and immune function of neonates using a porcine model. METHODS: Fourteen pairs of normal birth weight and IUGR piglets (7 days old) were randomly assigned to receive FORM or FORM supplemented with B. subtilis PB6 (FORM-BsPB6) for a period of 21 days. Blood samples, intestinal tissues and digesta were collected at necropsy and analysed for morphology, digestive enzyme activities, immune cell abundance, expression of genes associated with innate immunity and barrier function and microbial populations. RESULTS: Regardless of diet, IUGR significantly decreased average daily dry matter intake and average daily weight gain (P < 0.05). Moreover, IUGR significantly decreased plasma concentrations of immunoglobulin A, interleukin 1beta, count and percentage of blood lymphocytes (P < 0.05). Meanwhile, IUGR markedly decreased villous height and maltase activity, as well as mRNA abundance of Toll-like receptor 9 and Toll-interacting protein in the ileum (P < 0.05). Regardless of body weight, FORM-BsPB6 markedly decreased the feed conversion ratio (P < 0.05), due to better intestinal development, as indicated by increased villous height (P < 0.05), activities of maltase and sucrase in the intestine (P < 0.10). Moreover, both mRNA and protein abundances of zonula occludens-1 and claudin-1 in the ileum as well as the copy number of Bacillus in colonic digesta were increased (P < 0.05) in piglets fed FORM-BsPB6 relative to FORM. CONCLUSION: The results of this study indicate that IUGR delayed growth, intestinal development and immune function of piglets, while FORM-BsPB6 improved digestive capability and intestinal barrier function. PMID- 27188337 TI - Fe-MIL-101 exhibits selective cytotoxicity and inhibition of angiogenesis in ovarian cancer cells via downregulation of MMP. AB - Though metal-organic frameworks (MOFs) have inspired potential applications in biomedicine, cytotoxicity studies of MOFs have been relatively rare. Here we demonstrate for the first time that an easily available MOF, Fe-MIL-101, possesses intrinsic activity against human SKOV3 ovarian cancer cells and suppress the proliferation of SKOV3 cells (IC50 = 23.6 MUg mL(-1)) and normal mouse embryonic fibroblasts (BABL-3T3, IC50 = 78.3 MUg mL(-1)) cells. It was more effective against SKOV3 cells than typical anticancer drugs such as artesunate (ART, IC50 = 96.9 MUg mL(-1)) and oxaliplatin (OXA, IC50 = 64.4 MUg mL(-1)), but had less effect on normal BABL-3T3 cells compared with ART (IC50 = 36.6 MUg mL( 1)) and OXA (IC50 = 13.8 MUg mL(-1)). Fe-MIL-101 induced apoptosis of human umbilical vein endothelial cells (HUVECs) via G0/G1 cell cycle arrest and decreased the mitochondrial membrane potential in HUVECs and induced apoptosis. Furthermore, Fe-MIL-101 exhibited stronger antiangiogenic effects in HUVEC cells than antiangiogenic inhibitor (SU5416) via downregulation the expression of MMP 2/9. Our results reveal a new role of Fe-MIL-101 as a novel, non-toxic anti angiogenic agent that restricted ovarian tumour growth. These findings could open a new avenue of using MOFs as potential therapeutics in angiogenesis-dependent diseases, including ovarian cancer. PMID- 27188338 TI - Efficacy and safety of rituximab in Japanese patients with acquired thrombotic thrombocytopenic purpura refractory to conventional therapy. AB - Thrombotic thrombocytopenic purpura (TTP), while rare, is a potentially life threatening disorder. Plasma exchange (PE) is considered the primary treatment for TTP. In Western countries, rituximab, an anti-CD20 antibody, is recommended with PE for the treatment of refractory/relapsed TTP, and as up-front therapy in newly diagnosed TTP with neurological/cardiac pathology. The present open-label, single-arm, multicenter study evaluated the efficacy and safety of rituximab in Japanese patients with refractory/relapsed TTP. Patients received rituximab 375 mg/m(2) intravenously, once weekly for a total of four treatments, with PE and steroids. Of six evaluable patients in the full analysis set, two met the primary efficacy endpoint (platelet count >150 * 10(9)/L at week 4), yielding a 33.3 % response rate (95 % confidence interval: 4.3-77.7). While the lower confidence limit of the primary efficacy endpoint failed to reach the pre-specified threshold of 30 %, clinically significant recovery of platelet count with discontinuation of PE, increase of ADAMTS13 activity, disappearance of ADAMTS13 inhibitor, and improvement of TTP-associated clinical manifestations were observed after rituximab therapy in all patients. No safety concerns were identified in this study; therefore, rituximab is considered a useful treatment option in Japanese TTP patients who are refractory to conventional therapy. Trial registration JMA-IIA00160. PMID- 27188342 TI - Networking biofabricated systems through molecular communication. PMID- 27188341 TI - Reduced tonic inhibition after stroke promotes motor performance and epileptic seizures. AB - Stroke survivors often recover from motor deficits, either spontaneously or with the support of rehabilitative training. Since tonic GABAergic inhibition controls network excitability, it may be involved in recovery. Middle cerebral artery occlusion in rodents reduces tonic GABAergic inhibition in the structurally intact motor cortex (M1). Transcript and protein abundance of the extrasynaptic GABAA-receptor complex alpha4beta3delta are concurrently reduced (delta-GABAARs). In vivo and in vitro analyses show that stroke-induced glutamate release activates NMDA receptors, thereby reducing KCC2 transporters and down-regulates delta-GABAARs. Functionally, this is associated with improved motor performance on the RotaRod, a test in which mice are forced to move in a similar manner to rehabilitative training sessions. As an adverse side effect, decreased tonic inhibition facilitates post-stroke epileptic seizures. Our data imply that early and sometimes surprisingly fast recovery following stroke is supported by homeostatic, endogenous plasticity of extrasynaptic GABAA receptors. PMID- 27188340 TI - Prediction of Post-Concussive Behavioral Changes in a Rodent Model Based on Head Rotational Acceleration Characteristics. AB - Quantifying injury tolerance for concussion is complicated by variability in the type, severity, and time course of post-injury physiological and behavioral changes. The current study outlined acute and chronic changes in behavioral metrics following rotational acceleration-induced concussion in rats. The Medical College of Wisconsin (MCW) rotational injury model independently controlled magnitude and duration of the rotational acceleration pulse. Increasing rotational acceleration magnitude produced longer recovery times, which were used in this study and our prior work as an assessment of acute injury severity. However, longer duration rotational accelerations produced changes in emotionality as measured using the elevated plus maze. Cognitive deficits were for the most part not apparent in the Morris water maze assessment, possibly due to the lower severity of rotational acceleration pulses incorporated in this study. Changes in emotionality evolved between acute and chronic assessments, in some cases increasing in severity and in others reversing polarity. These findings highlight the complexity of quantifying injury tolerance for concussion and demonstrate a need to incorporate rotational acceleration magnitude and duration in proposed injury tolerance metrics. Rotational velocity on its own was not a strong predictor of the magnitude or type of acute behavioral changes following concussion, although its combination with rotational acceleration magnitude using multivariate analysis was the strongest predictor for acute recovery time and some chronic emotional-type behavioral changes. PMID- 27188344 TI - [Survey of the first case of Zika virus disease in the mainland of China]. AB - OBJECTIVE: To analyze epidemiological characteristics of the first laboratory confirmed case of Zika virus disease in the mainland China, and provide evidence for the prevention and control of the spread of Zika virus disease. METHODS: Epidemiological survey was conducted for the first suspect case of Zika virus disease in China, and medical observation was conducted for the close contacts. The nucleic acid detection of Zika virus was conducted with Real-time RT-PCR by using blood and urine samples collected from the cases. RESULTS: The first case of Zika virus disease was confirmed. The case was cured and discharged on 18(th) day after the onset. The blood sample on 10(th) day after the onset and urine samples on 11-13(th) days after the onset were all positive for Zika virus. The case had the history of mosquito bites in the endemic country before the onset. The close contacts showed no Zika virus disease-like symptoms during the medical observation period. CONCLUSION: The case reported by Jiangxi province was the first imported case of Zika virus disease in the mainland of China. The infection was related with the mosquito bites in Venezuela where Zika virus disease in endemic. PMID- 27188345 TI - [Survey of the third Zika virus disease case in the mainland of China]. AB - OBJECTIVE: To evaluate the performance of Zika virus(ZIKV)disease prevention and control. METHODS: Descriptive epidemiological analysis was conducted on the clinical manifestations, laboratory detection results and disease progression of the third imported ZIKV disease case in the mainland of China. RESULTS: On 19 February 2016, a ZIKV disease case was confirmed in Yiwu, Zhejiang province, which was the third imported case of ZIKV disease confirmed by China CDC laboratory and expert consulting. The patient just had a travel to Fiji and Samoa and had mosquito bite history in Samoa. The patient was hospitalized on 16 February after the onset on 14 February and the eruption on 15 February. The body temperature of the patient became normal on 17 February, the rash disappeared on 19 February and the conjunctivitis resolved on 20 February. The positive detection of the viral nucleic acid in blood was only for 3 consecutive days, and the viral nucleic acid could be detected in urine even after negative detection in blood for 4 days. CONCLUSION: The symptoms of the patient were typical. ZIKV can be detected by using blood sample in early phase, but after body temperature become normal, the virus can be detected in urine. PMID- 27188346 TI - [Infestation status Aedes albopictus and related mosquito-borne infectious disease risk in central urban area in Shanghai]. AB - OBJECTIVE: To evaluate Aedes albopictus infestation status in the central urban area of Shanghai, and analyze the related epidemic risk of mosquito-borne infectious disease. METHODS: Consecutive mosquito surveillance was conducted in the green lands and residential areas in the central urban area of Shanghai during 2012-2014, the Aedes albopictus density and its seasonal fluctuation were observed; the sequence of Aedes albopictus in Shanghai was aligned with that in other epidemic area abroad, and the susceptibility of Aedes albopictus to mosquito-borne virus and endemic risk were analyzed. RESULTS: No Aedes aegypti was found in the central urban area of Shanghai. As predominant species in both the residential area and the green lands, the proportion of Aedes albopictus in the residential area was significantly higher than that in the green lands(78.53% vs. 19.99%, chi(2) =15 525.168, P<0.001), and so was the density(11.91, 42.02 pcs/day . site in the residential area vs. 3.65, 2.18, 2.73 pcs/day . site in the green lands, all P value <0.001). In 2014, the density reached 42.02 pcs/day . site and the proportion reached 94.69% in the residential areas. Phylogenetic tree analysis showed that the genetic distance between Aedes albopictus in Shanghai and Aedes albopictus in Africa was quite far. CONCLUSION: No Aedes aegypti was found in Shanghai and its surrounding areas, while Aedes albopictus infestation in the central urban area of Shanghai was serious. Strict measures should be taken to reduce the Aedes albopictus density for the effective control Zika virus spread. PMID- 27188343 TI - Metabolomics Investigation Reveals Metabolite Mediators Associated with Acute Lung Injury and Repair in a Murine Model of Influenza Pneumonia. AB - Influenza virus infection (IVI) can cause primary viral pneumonia, which may progress to acute lung injury (ALI) and respiratory failure with a potentially fatal outcome. At present, the interactions between host and influenza virus at molecular levels and the underlying mechanisms that give rise to IVI-induced ALI are poorly understood. We conducted a comprehensive mass spectrometry-based metabolic profiling of serum, lung tissue and bronchoalveolar lavage fluid (BALF) from a non-lethal mouse model with influenza A virus at 0, 6, 10, 14, 21 and 28 days post infection (dpi), representing the major stages of IVI. Distinct metabolite signatures were observed in mice sera, lung tissues and BALF, indicating the molecular differences between systematic and localized host responses to IVI. More than 100 differential metabolites were captured in mice sera, lung tissues and BALF, including purines, pyrimidines, acylcarnitines, fatty acids, amino acids, glucocorticoids, sphingolipids, phospholipids, etc. Many of these metabolites belonged to pulmonary surfactants, indicating IVI induced aberrations of the pulmonary surfactant system might play an important role in the etiology of respiratory failure and repair. Our findings revealed dynamic host responses to IVI and various metabolic pathways linked to disease progression, and provided mechanistic insights into IVI-induced ALI and repair process. PMID- 27188339 TI - Erectile dysfunction. AB - Erectile dysfunction is a multidimensional but common male sexual dysfunction that involves an alteration in any of the components of the erectile response, including organic, relational and psychological. Roles for nonendocrine (neurogenic, vasculogenic and iatrogenic) and endocrine pathways have been proposed. Owing to its strong association with metabolic syndrome and cardiovascular disease, cardiac assessment may be warranted in men with symptoms of erectile dysfunction. Minimally invasive interventions to relieve the symptoms of erectile dysfunction include lifestyle modifications, oral drugs, injected vasodilator agents and vacuum erection devices. Surgical therapies are reserved for the subset of patients who have contraindications to these nonsurgical interventions, those who experience adverse effects from (or are refractory to) medical therapy and those who also have penile fibrosis or penile vascular insufficiency. Erectile dysfunction can have deleterious effects on a man's quality of life; most patients have symptoms of depression and anxiety related to sexual performance. These symptoms, in turn, affect his partner's sexual experience and the couple's quality of life. This Primer highlights numerous aspects of erectile dysfunction, summarizes new treatment targets and ongoing preclinical studies that evaluate new pharmacotherapies, and covers the topic of regenerative medicine, which represents the future of sexual medicine. PMID- 27188347 TI - [Relationship between overweight/obesity and hypertension among adults in China: a prospective study]. AB - OBJECTIVE: To evaluate the influence of overweight/obesity on the incidence of hypertension among adults in China. METHODS: The subjects of this prospective study were 13 739 Chinese adults aged 35-74 years recruited at the baseline surveys of China Multicenter Collaborative Study of Cardiovascular Disease Epidemiology and International Collaborative Study of Cardiovascular Disease in Asian. Baseline surveys were conducted in 1998 and during 2000-2001, respectively, and the follow-up was conducted during 2007-2008. According to the body mass index, the subjects were divided into four groups: underweight group(<18.5 kg/m(2)), normal weight group(18.5-23.9 kg/m(2)), overweight group(24.0-27.9 kg/m(2))and obesity group(>=28.0 kg/m(2)). Age-standardized cumulative incidence of hypertension was calculated for each group, respectively. The relative risks(RRs)and 95% confidence intervals(CIs)for the incidence of hypertension of underweight, overweight and obesity groups were estimated by using generalized linear regression model with normal weight group as reference. RESULTS: During 8.1 years of follow-up, 4 271 hypertension cases were detected(2 012 in men and 2 259 in women). Age-standardized cumulative incidence of hypertension for the underweight, normal weight, overweight and obesity groups were 20.3%, 30.9%, 43.6% and 50.8% in men, respectively; and 22.9%, 30.4%, 41.1% and 50.8% in women, respectively. Compared with the normal weight group, multivariate-adjusted RR(95% CI)for the incidence of hypertension in underweight, overweight and obesity groups were 0.78(0.64-0.95), 1.22(1.13-1.30)and 1.28(1.16 1.42)in men, respectively; and 0.89(0.77-1.03), 1.16(1.09-1.23)and 1.28(1.18 1.38)in women, respectively. The overweight and obese subjects had higher risk for the incidence of hypertension, with the population attributable risk proportion of 7.4% in men and 8.8% in women, respectively. CONCLUSION: Overweight or obese people are at an increased risk of developing hypertension, thus prevention and control of overweight/obesity are needed to reduce hypertension incidence among adults in China. PMID- 27188348 TI - [Study on effects of community-based management of hypertension patients aged >=35 years and influencing factors in urban and rural areas of China, 2010]. AB - OBJECTIVE: To understand the effects of standardized community-based management of hypertension in urban and rural areas in China and related influencing factors. METHODS: The study subjects were the hypertension patients aged >=35 years who were recruited in 2011 from the participants of 2010 national chronic and non-communicable disease surveillance project. The hypertension patients were diagnosed in community health centers or higher level hospitals and included in community based hypertension management project. By face-to-face questionnaire survey and health examination, the information of the subjects' demographic characteristics, risk factors, complications, involvement in community-based management of hypertension, anti-hypertension treatment, blood pressure, body height, waistline and body weight were collected. In this study, Rao-Scott chi(2) test was used to compare the variations among sub-groups. Taylor series linearization method was used to estimate the prevalence rate. The complex sampling and unconditional multivariate logistics regression analysis was conducted to identify the influencing factors for the control of hypertension. RESULTS: A total of 5 120 subjects were recruited in the analysis. The proportion of those receiving management for more than two years was 36.57%, and it was higher in urban area(44.56%)than in rural area(31.79%, P<0.05); In the past 12 months, 6.17% and 14.46% of the patients received no blood pressure measurement and drug therapy advice respectively, but there were no significant differences between urban group and rural group(P>0.05); In the past 12 months, the proportions of the patients receiving diet and physical activity advice were 84.25% and 84.90% respectively, and the proportions were higher in urban group than in rural group(P<0.05); In the past 12 months, the proportions of the subjects receiving tobacco and alcohol use advice were 78.41% and 77.80% respectively, and the proportions were higher in rural group than in urban group(P<0.05). In urban area, the subjects receiving standardized management had lower SBP(142.79+/-17.39)mmHg, lower DBP(84.26+/-9.49)mmHg and higher blood pressure control rate(49.77%)than those receiving no standardized management(P<0.05); while in rural area, no difference was found in BP control between the patients receiving and receiving no standardized management(P>0.05). In urban area, the influencing factors for BP control among the subjects receiving community based management were educational level, annual income, body weight, hypertension management mode, times of receiving BP measurement, times of receiving antihypertensive medicine advice and receiving physical activity advice; while in rural area, the influencing factors for BP control among the subjects receiving community based management were annual income, body weight, family history of hypertension, antihypertensive medicine awareness, times of receiving antihypertensive medicine advice and receiving diet advice. CONCLUSION: The effects of community-based standardized management of hypertension were better in urban area than in rural area, and the quality of the services of community-based hypertension management was lower in rural area than in urban area. PMID- 27188349 TI - [Influences of genetic and environmental factors on smoking related behaviors among male twin adults in China]. AB - OBJECTIVE: To analyze the influences of genetic and environmental factors on smoking behavior, smoking cessation and onset age of smoking less than 20 years in male twin adults. METHODS: A face-to-face questionnaire was conducted to collect data from 6 458 pair male twins aged >=25 years registered in 9 provinces(municipality)in China. The heritability of three smoking related behaviors were calculated by using structural equation models. RESULTS: The ACE models were the best models of the three dimensions of smoking, i.e. smoking behavior, smoking cessation and onset age of smoking less than 20 years for male twins, and the corresponding heritability of these behaviors were 0.26(0.19 0.34), 0.27(0.19-0.37)and 0.05(0.00-0.14), respectively. When adjusted for area and age, the heritability of these three behaviors were 0.26(0.19-0.34), 0.31(0.00-0.74)and 0.05(0.00-0.14), respectively. CONCLUSIONS: All the three smoking related behaviors were affected by genetic factors, but environment factors had more effect on them. For smoking cessation, the heritability was highest, but the influence of environmental factors was lowest. Meanwhile, for onset age of smoking, the influence of environmental factors was highest. PMID- 27188350 TI - [Study on incidence and risk factors of fall in the elderly in a rural community in Beijing]. AB - OBJECTIVE: To investigate the incidence of fall in the old farmers of Miyun county in Beijing. METHODS: The old farmers who lived in Jugezhuang and Fengjiayu townships of Miyun county were selected for a questionnaire survey to collect the information about the incidence of fall and their health status. RESULTS: A total of 2 397 old farmers, including 967 males and 1 430 females, were surveyed. Fall occurred in 347 old farmers(14.5%). The difference in the incidence of fall was significant between males(9.6%)and females(17.8%). A total of 282 falls occurred in courtyards, 45 falls occurred in field/hilly areas. Among the falls occurred, 216(27.2%)led to injuries. The most common site of injuries was hip(45 falls). Logistic regression analysis showed that physical exercise and high income were protective factors, but difficult standing up and walking, visual problem and stroke were the risk factors. In the males, the special risk factor was mid cognitive impairment, and in the females, the special risk factor was urinary incontinence, but afternoon nap was a protective factor. CONCLUSION: The incidence of fall in the rural community was relatively high with distinct area distribution, which has caused serious influence on the mental and physical health of the elderly. PMID- 27188351 TI - [Road-side observational survey on 4 unlawful acts among electric bicycle riders in Zhejiang]. AB - OBJECTIVE: To investigate the prevalence of key unlawful acts among electric bicycle riders and provide evidence for the development of specific interventions. METHODS: A 4-day road-side survey was conducted in Jinhua, Zhejiang province, in 2013. The speed of electric bicycle was measured by speed measuring instrument and the unlawful acts of riders, such as reverse riding, running the red-light and carrying passengers, were observed with non participatory way. RESULTS: A total of 3 448 running electric bicycles were observed and the average speed was 26 km/h, the proportion of electric bicycle at the speed of >=15 km/h was 87.06%. The average speed was highest during 10 am-11 am(30 km/h). the number of observed electric bicycle riders with unlawful acts of ' running the red-light','reverse riding' and ' carrying passengers' were 1 315, 656 and 1 877 respectively, and the estimated rate was 10.01%, 4.99% and 15.22%, respectively. More ' running the red-light','reverse riding' and ' carrying passengers' occurred during 7 am-8 am(14.59%)and 13 pm-14 pm(15.25%), 13 pm-14 pm(7.33%)and 17 pm-18 pm(7.63%), 6 am-7 am(32.44%)and 12 pm-13 pm(27.90%), respectively. CONCLUSION: Overspeeding, carrying passengers, running the red light, reverse riding were the key unlawful acts among electric bicycle riders. Targeted intervention should be carried out to reduce the prevalence of unlawful riding acts and the incidence of electric bicycle related injuries and deaths. PMID- 27188352 TI - [Efficacy of antiretroviral therapy and influencing factors for people living with HIV/AIDS in designated hospitals in Harbin]. AB - OBJECTIVE: To understand the efficacy of antiretroviral therapy for people living with HIV/AIDS and influencing factors; and provide evidence to improve the treatment of HIV infection and AIDS for the better life of the patients. METHODS: A cross sectional study was conducted in designated AIDS hospitals in Harbin. A questionnaire was used to collect the information of the patients receiving treatment in these hospitals. The statistical analysis was done with software SAS 9.2 and Excel 2010. Univariate analysis was performed with t test and multivariate analysis was performed with ordinal logistic regression model. Wilcoxon ranks sum test was conducted to compare the CD4(+) T lymphocyte counts. RESULTS: The number of the patients receiving antiretroviral therapy was in increase in recent years. The HIV infection route was mainly homosexual contact. The CD4(+)T lymphocyte count of the patients increased at different levels after >=6 months treatment(P<0.01). Household income(P<0.05), adherence to treatment plan or not(P<0.05), social relationship(P< 0.05), concern of economic cost(P<0.01)medication compliance(P<0.01)and initial level of CD4(+) T lymphocyte(P<0.01)were the influencing factors for antiretroviral therapy efficacy. CONCLUSION: In designated hospitals in Harbin, the number of the patients receiving HIV antiretroviral therapy kept to increase and the efficacy of the treatment was obvious. PMID- 27188353 TI - [Prevalence of depression and related factors in 180 HIV/AIDS patients receiving highly active antiretroviral therapy]. AB - OBJECTIVE: To understand the prevalence of depression in HIV/AIDS patients who are receiving highly active antiretroviral therapy(HAART), and identify the influencing factors for depression. METHODS: A total of 180 HIV/AIDS outpatients receiving HAART were recruited in a cross-sectional survey at the first hospital of Changsha from June to December 2015. The SDS questionnaire(SDS score>=50)was used to screen depression patients and psychological CT was used to confirm the depression. The influencing factors were identified through multivariate logistic analysis. RESULTS: Forty eight patients showed depressive symptoms in preliminary screening(26.67%), and 33 patients were diagnosed with depression(18.33%). HIV/AIDS related stigma and discrimination scale score 20-40(OR=0.093, 95%CI: 0.020-0.431)was the protective factors. Living alone(OR=5.062, 95% CI: 1.626 15.764), HIV related diseases in recent three months(OR=3.778, 95% CI: 1.113 12.826)were the risk factors. CONCLUSION: More attention should be paid to the depression in HIV/AIDS patients receiving HAART. The mental health care for these patients needs to be improved in clinic practice. PMID- 27188354 TI - [The prevalence of primary HIV-1 drug resistance in newly reported HIV infections in Henan]. AB - OBJECTIVE: To study the prevalence of primary HIV-1 drug resistance in newly reported HIV infected individuals receiving no antiviral treatment in Henan. METHODS: Network direct reporting information of newly reported HIV infection cases in six cities of Henan during January to June, 2013 and January to June, 2014 were collected, and blood samples were collected from the cases to conduct genotypic drug resistance test and sequence analysis. RESULTS: Primary HIV-1 drug resistance was detected in 45 of 624 newly reported HIV infection cases, the prevalence of primary HIV-1 drug resistance was 7.21%, which was classified as moderate. Univariate analysis revealed that the prevalence of primary HIV-1 drug resistance was higher in females(chi(2)=11.463, P = 0.001), in age group <20 years(chi(2)=8.969, P=0.011), in illiterates(chi(2)=18.072, P=0.001)and in cases of HIV subtype B infection(chi(2)=9.897, P=0.019). Multi-univariate analysis revealed that the risk of primary HIV-1 drug resistance was high in females(OR=2.194, 95%CI: 1.111-4.331). Non-nucleoside reverse transcriptase inhibitor(NNRTI), Nucleoside reverse transcriptase inhibitor(NRTI)and Protease inhibitor(PI)resistance mutations were found in 4.97%, 3.53% and 1.12% of the cases, respectively. M184V/I(2.08%)and K103N/S(2.88%)were the most commonly emerged NRTI and NNRTI resistance mutation. Multiple NRTI resistance mutation was found in four cases. HIV subtype B infections accounted for largest proportion(51.76%, 323/624), followed by CRF07_BC cases(23.72%, 148/624)and CRF01_AE cases(19.71%, 123/624). CONCLUSION: The prevalence of primary HIV-1 drug resistance was moderate in the newly reported HIV infected individuals in Henan. The surveillance for HIV-1 drug resistance transmission should be strengthened and drug resistance test before the antiviral treatment should be given. PMID- 27188355 TI - [Overdose of heroin and influencing factors in intravenous drug users in parts of Yunnan]. AB - OBJECTIVE: To assess the prevalence of overdose of heroin and risk factors in intravenous drug users(IDUs)in Yunnan Province. METHODS: During July-August of 2015, IDUs were recruited from four methadone maintenance treatment(MMT)clinics and two compulsory drug rehabilitation centers in Honghe and Dehong prefectures, Yunnan province. The information about IDUs ' demographic characteristics and drug use history, overdose of heroin in previous12 months and the latest overdose of heroin were collected through face to face questionnaire survey. The factors associated with overdose of heroin were evaluated with logistic regression models. RESULTS: Of the 340 IDUs surveyed, 85.3%(290/340)were males, the mean age was 37.7+/-8.7 years, 65.6%(223/340)were Han ethnicity, and 49.4%(167/338)were HIV positive, 22.6%(77/340)reported having used club-related drugs(such as ephedrine, methamphetamine, benzodiazepines and ketamine)in the previous 12 months. Of the 340 IDUs, 41.8%(142/340)had at least one overdose of heroin in their lifetime(median: 3 overdoses)and 15.6%(53/340)had at least one overdose of heroin(median : 1 overdose use)in previous 12 months. The mean age of the 53 IDUs was(36.7 +/- 8.4)years, and 83.0%(44/53)of them were males, the average drug use history was(16.5 +/- 7.6)years. Dosage increase(26.4%, 14/53)and multidrug use(28.3%, 15/53)were the main causes for overdose of heroin. Multiple logistic regression analysis indicated that methadone maintenance treatment during the past year(OR=0.534, 95%CI: 0.290-0.980)was independently associated with decreased risk of overdose of heroin, needle sharing in the past 6 months(OR=2.735, 95%CI: 1.383-5.407)and being forced to receive drug rehabilitation for less than one year(OR=2.881, 95% CI: 1.226-6.767)were independently associated with increased risk of overdose of heroin. CONCLUSION: Overdose of heroin is common among IDUs in Yunnan. It is necessary to encourage IDUs to receive MMT and strengthen the health education about the prevention of overdose of heroin, especially before they leave drug rehabilitation centers. And it is important to establish a referral mechanism from drug rehabilitation center to MMT clinic for drug users. PMID- 27188356 TI - [HCV infection status and risk factors in remunerated blood donors in Jiangsu province]. AB - OBJECTIVE: To investigate the infection status of HCV in remunerated blood donors and risk factors in Jiangsu province. METHODS: A Cross-sectional study was conducted among people aged >50 years. Questionnaires were used to collect the information about their demographic characteristics and risk behaviors, and venous blood samples were collected from them to detect HCV anti-body, HCV-RNA and other biochemical indicators. EpiData and Stata were used for data entry and statistical analysis. RESULTS: The overall HCV sero-prevalence rates were 22.55% and 61.05% among remunerated blood donors. Data from multiple stepwise regression analysis showed that alanine aminotransferase(ALT)(adjusted OR=1.38, 95%CI: 1.18 1.62)and aspartate aminotransferase(AST)(adjusted OR=1.30, 95%CI: 1.10-1.54)were associated with the outcomes of HCV infection, and fasting plasma glucose(adjusted OR=1.17, 95%CI: 1.01-1.35)were associated with HCV RNA viral loads. CONCLUSION: The prevalence of HCV infection in remunerated blood donors was high, clinical ALT, AST and fasting plasma glucose levels were associated with the risk for HCV infection and HCV RNA viral load. PMID- 27188357 TI - [A sero-epidemiological study of hepatitis B among general population in Beijing]. AB - OBJECTIVE: To understand the sero-prevalence of hepatitis B in general population in Beijing and provide evidence for the prevention and control of hepatitis B. METHODS: A serological survey was conducted in general population aged >1 year selected through multistage randomized cluster sampling in Beijing from August 2013 to February 2014. The estimated sample size was 5 200. Venous blood samples were collected from them to detect five hepatitis B serological indicators. The information about the hepatitis B immunization history and risk factors of the study subjects were collected through a questionnaire survey. RESULTS: A total of 6 705 people were surveyed. The sero-positive rates of HBsAg, anti-HBs, anti-HBc and total HBV infection rate were 2.74%, 44.72%, 26.91% and 26.95% respectively. The age standardized rates were 2.73%, 44.83%, 26.84% and 26.87% respectively. As for the general population, in Beijing since the prevalence rate of hepatitis B surface antigen has decreased to 2.73%, <1% in children aged less than 5 years old, <1% in people aged less than 25 years old. CONCLUSION: The integrated prevention and control strategy of hepatitis B had a significant effect in Beijing. We should continue to strengthen the work of adult hepatitis B vaccination. PMID- 27188358 TI - [Dynamic maternal measles antibody level in infants: a longitudinal study]. AB - OBJECTIVE: To understand the dynamic maternal measles antibody level in infants in Guangzhou. METHOD: Women who delivered babies in a maternal and child health care hospital in Guangzhou and their infants who were never affected by measles were included in our study. All the serum samples collected from mothers and infants were tested by using enzyme linked immunosorbent assay(ELISA)for the quantitative measurement of measles IgG antibodies. A longitudinal sero epidemiological study was conducted to investigate the duration of the presence of measles maternal antibodies in infants based on the measurement at different time points(0, 3, 5, 7 month). RESULT: A total of 689 mothers and their 691 infants(two pairs of twins)were included in the study. The concentration and the sero-positivity rate of measles antibody in mothers was 513.8 mIU/ml and 81.6% respectively. The concentration and the sero-positivity rate of measles antibody in infants was 732.8 mIU/ml and 87.3%, respectively. The measles antibody levels of newborns were positively associated with those of mothers(r=0.917 5, P<0.001), which declined rapidly at 3 months after birth and mostly turned to be negative at 7 months after birth. Measles antibody turned be negative at 3 months after birth in low, middle level groups, but remained to be positive in high level group at 5 months after birth. CONCLUSION: The maternal measles antibody could rarely protect infants at age of 8 months even though mother had been vaccinated or acquired natural immunity. It is suggested to adjust the time of the first dose measles vaccination in infants and increase the measles antibody level of child bearing aged women to reduce the incidence of measles in infants. PMID- 27188359 TI - [Big data analysis of flow of tuberculosis cases in China, 2014]. AB - OBJECTIVE: To describe the flow of tuberculosis(TB)cases for medical care in China in 2014. METHODS: The analysis and visualization of reported flow of TB cases were conducted with software R to indicate the case distribution/flow and the levels of hospital where TB cases sought medical care in different provinces. RESULTS: In a province, the TB cases mainly flowed to the province capital, but the inter-provincial flow was mainly to neighbor provinces and from central or western provinces to eastern provinces(municipality), such as Beijing, Shanghai and Guangdong. The grade III(A)hospitals were the choice of most TB cases seeking medical care in other provinces. CONCLUSION: The epidemic situation of TB in China is still serious, and the flow of TB cases would facilitate the spread of the disease. It is necessary to strengthen the research on influence of TB case flow for seeking medical care on the spread of TB to provide evidence for better TB prevention and control. PMID- 27188360 TI - [Analysis on antiretroviral therapy efficacy for HIV/AIDS in Zhejiang province, 2009-2014]. AB - OBJECTIVE: To analyze the efficacy of highly active antiretroviral therapy(HAART)for HIV/AIDS in Zhejiang province from 2009 to 2014. METHODS: A retrospective cohort study was conducted among patients with access to HAART aged <15 years from 2009 to 2014 through descriptive epidemiological analysis on the patients' demographic characteristics, HAART efficacy. The immune recovery Kaplan Meier curves were drawn by using baseline CD(4) T lymphocytes cell(CD(4))data. The influencing factors for virus suppression were analyzed by using logistic regression model. RESULTS: There were 9 594 patients with access to HAART in Zhejiang from 2009 to 2014. The' average age of the patients was 38.7 years old, the male to female ratio was 4.11?1. Heterosexual(55.9%)and homosexual(40.0%)contacts were the main transmission routes. Baseline CD(4) count 200-349 cells/MUl was found in 45.4% of the patients, the median of the CD(4) count was 221(IQR: 123-298). The median of time for CD(4) recovery in patients with baseline CD(4) count <200 cells/MUl was 3.48 and 11.58 times higher than the patients with baseline CD(4) count 200-349 cells/MUl and baseline CD(4) count >=350 cells/MUl. Univariate and multivariate logistic regression analyses showed that marital status, HAART regimen, treatment miss in last week and CD(4) recovery were major influencing factors for HAART efficacy. CONCLUSIONS: HAART had good treatment effecacy in HIV/AIDS patients in Zhejiang. The baseline CD(4) count and adherence to HAART were the most important influencing factors. It is recommended to take measures to expand HIV screening and HAART coverage, conduct HAART adherence education, and strengthen the special care for high-risk groups to improve the HAART efficacy in Zhejiang province. PMID- 27188361 TI - [Epidemiology of pertussis in adults and related factors in Tianjin, 2005-2014]. AB - OBJECTIVE: To understand the epidemiological characteristics of pertussis in adults and related factors in Tianjin. METHODS: Descriptive epidemiological analysis was conducted by using the epidemiological data of pertussis in adults in Tianjin during 2005-2014. The transmission routes of family cluster cases were analyzed. ELISA was conducted to detect pertussis immunity levels in adults aged 18-83 years. RESULTS: The pertussis cases in adults accounted for 28.57%(252/882)of the total cases in Tianjin , the annual incidence of pertussis in adults was 0.16/100 000. The highest incidence was 0.46/100 000 in 2013. The age specific proportion of the cases was highest in age group 21-30 years(36.12%, 91/252). Three household transmission routes of pertussis were identified, the major one was adult-to-infant(77.78%,98/126). The parents were the infection sources of 81.64% of infant cases(80/98). Of the 904 study subjects, the average positive rate of antibody against pertussis was 55.20%(95%CI: 51.96%-58.44%). There were significant differences in antibody positive rate among different age groups(P= 0.015), and which had the linear correlation with the reported annual incidence(r=0.98, P=0.003)and showed upward trend(chi(2)=11.79, P=0.001). CONCLUSION: The study indicated that adults have become the population at high risk for pertussis and the major infection sources for infants in Tianjin. The positive rate of antibody against pertussis was low in adults. It is suggested to conduct pertussis vaccination in adults. PMID- 27188362 TI - [Spatial analysis of autumn-winter type scrub typhus in Shandong province, 2006 2014]. AB - OBJECTIVE: To discuss the spatial-temporal distribution and epidemic trends of autumn-winter type scrub typhus in Shandong province, and provide scientific evidence for further study for the prevention and control of the disease. METHODS: The scrub typhus surveillance data during 2006-2014 were collected from Shandong Disease Reporting Information System. The data was analyzed by using software ArcGIS 9.3(ESRI Inc., Redlands, CA, USA), GeoDa 0.9.5-i and SatScan 9.1.1. The Moran' s I, log-likelihood ratio(LLR), relative risk(RR)were calculated and the incidence choropleth maps, local indicators of spatial autocorrelation cluster maps and space scaning cluster maps were drawn. RESULTS: A total of 4 453 scrub typhus cases were reported during 2006-2014, and the annual incidence increased with year. Among the 17 prefectures(municipality)in Shandong, 13 were affected by scrub typhus. The global Moran's I index was 0.501 5(P<0.01). The differences in local Moran' s I index among 16 prefectures were significant(P<0.01). The " high-high" clustering areas were mainly Wulian county, Lanshan district and Juxian county of Rizhao, Xintai county of Tai' an, Gangcheng and Laicheng districts of Laiwu, Yiyuan county of Zibo and Mengyin county of Linyi. Spatial scan analysis showed that an eastward moving trend of high-risk clusters and two new high-risk clusters were found in Zaozhuang in 2014. The centers of the most likely clusters were in the south central mountainous areas during 2006-2010 and in 2012, eastern hilly areas in 2011, 2013 and 2014, and the size of the clusters expanded in 2008, 2011, 2013 and 2014. One spatial-temporal cluster was detected from October 1, 2014 to November 30, 2014, the center of the cluster was in Rizhao and the radius was 222.34 kilometers. CONCLUSION: A positive spatial correlation and spatial agglomerations were found in the distribution of autumn-winter type scrub typhus in Shandong. Since 2006, the epidemic area of the disease has expanded and the number of high-risk areas has increased. Moreover, the eastward moving and periodically expanding trends of high-risk clusters were detected. PMID- 27188363 TI - [Study on influence of floods on bacillary dysentery incidence in Liaoning province, 2004 -2010]. AB - OBJECTIVE: To understand the influence of floods on bacillary dysentery in Liaoning province. METHODS: The monthly surveillance data of bacillary dysentery, floods, meteorological and demographic data in Liaoning from 2004 to 2010 were collected. Panel Poisson regression analysis was conducted to evaluate the influence of floods on the incidence of bacillary dysentery in Liaoning. RESULTS: The mean monthly morbidity of bacillary dysentery was 2.17 per 100 000 during the study period, the bacillary dysentery cases mainly occurred in during July September. Spearman correlation analysis showed that no lagged effect was detected in the influence of floods on the incidence of bacillary dysentery. After adjusting the influence of meteorological factors, panel data analysis showed that the influence of floods on the incidence of bacillary dysentery existed and the incidence rate ratio was 1.439 4(95%CI: 1.408 1-1.471 4). CONCLUSION: Floods could significantly increase the risk of bacillary dysentery for population in Liaoning. PMID- 27188364 TI - [Prediction of 10-year risk for ischemic cardiovascular disease in adults aged >=35 years in China]. AB - OBJECTIVE: To estimate the 10-year risk for ischemic cardiovascular disease(ICVD)in adults aged >=35 years. METHODS: In 2010, we conducted a cross sectional survey among 98 712 adults aged >=18 years selected through using multi stage stratified cluster random sampling, and 67 214 adults without ICVD history and aged >=35 years were recruited as study subjects. Their information on cardiovascular disease history and related behavior risk factors, including smoking, hypertension and diabetes diagnosis history were collected through face to-face questionnaire interview, health examination and laboratory detection. The 10-year risk for ICVD in this group was evaluated according to the China 10-year risk for ICVD score tables. RESULTS: The average score and 10-year risk for ICVD in the adults aged >=35 years were 5.1(95% CI: 4.9-5.2)and 4.2%(95% CI: 4.0% 4.4%), respectively. A total of 8.5% of the adults aged >=35 years had high 10 year risk for ICVD(95%CI: 7.8%-9.2%). This proportion was 12.1% for males(95%CI: 11.1%-13.0%)and 4.9% for females(95%CI: 4.4%-5.5%)(P<0.05), 8.8% for those living in rural areas(95%CI: 7.8%-9.7%)and 8.1% for those living in urban areas(95%CI: 7.2%-8.9%)(P<0.05). About 19.1% and 72.4% of adults had middle and low 10-year risk for ICVD, respectively(95%CI: 18.2%-20.0%, 95%CI: 70.9%-73.9%). The proportion of the adults with high and middle risk for ICVD in 10 years was higher among those with lower educational level or with lower income level(P<0.05). CONCLUSION: About 8.5% of the adults aged >=35 years in China have high 10-year risk for ICVD. Being male, living in rural area, with lower education or lower income levels were related with the higher 10-year risk for ICVD. PMID- 27188366 TI - [Incidence trends of cervical cancer in Tianjin, 2007-2013]. AB - OBJECTIVE: To investigate the change of incidence and age distribution of cervical cancer in Tianjin from 2007 to 2013. METHODS: The incidence data of cervical cancer and population data were collected from the cancer registry system of Tianjin Center for Disease Control and Prevention and Tianjin Municipal Public Security Bureau, respectively. The crude incidence, and age-standardized incidence of cervical cancer were calculated by using SPSS software. The Join Point Regression Program software was used to detect the trend of cervical cancer incidence. RESULTS: A total of 3 362 cervical cancer patients were diagnosed during 2007 to 2013. The average age of the patients was 48.11 years. The crude incidence was 9.85/100 000. The annual world standard age specific incidence was 6.65 /100 000. The incidence in urban area was higher than that in rural area, but the proportion of the cases in urban area showed a downward trend(trend chi(2)=21.92, P=0.001)and the proportion of the cases in rural area showed a upward trend(trend chi(2)=12.70, P=0.048). The difference was significant. The incidence was generally stable in urban area, the APC value was 2.7%(95%CI:-9.1% 16.2%), the difference was not significant(Z=0.564, P=0.597); The incidence rate in rural area showed an upward trend, APC value was 13.4%(95% CI: 3.5%-24.2%), the difference was significant(Z=3.549, P=0.016). The two incidence peaks were in age groups 40-44 years and 75-79 years. CONCLUSION: The overall incidence of cervical cancer in Tianjin was still stable during 2007-2013, and the disease mainly occurred in middle-aged and elderly population. More attention should be paid to the increased incidence of cervical cancer in rural area. PMID- 27188365 TI - [Morbidity and mortality of malignant tumor in Zhejiang province, 2014]. AB - OBJECTIVE: To analyze the morbidity and mortality of malignant tumor in Zhejiang province in 2014. METHODS: The data were collected from Zhejiang provincial chronic disease surveillance system in 2014. The crude rate, age-standardized rate, cumulative rate(0-74 years old), cut rate(35-64 years old), age-specific and area-specific morbidity/mortality as well as the constitution of top 10 leading cancers were then calculated and analyzed. The age-standardized rate was calculated according to the standard population in China in 1982 and the Segi' s world standard population. RESULTS: The crude morbidity was 348.80/100 000(370.74/100 000 in males and 326.51/100 000 in females). The age-standardized morbidity according to the standard population in China and according to world standard population were 168.84/100 000 and 217.23/100 000 respectively, the cumulative morbidity was 24.66% and the cut morbidity was 376.40/100 000. Age specific morbidity in age group 0-34 years remained low; however, the morbidity increased obviously in age group >=35 years, increased more rapidly in age group >=50 years and finally reached the peak in age group 80-84 years(1 618.20/100 000). The morbidity of malignant tumor, age-standardized morbidity(China standard)and age-standardized morbidity(world standard)were 381.81/100 000, 185.15/100 000 and 236.27/100 000 respectively in urban area, and 330.23/100 000 , 159.47/100 000 and 206.29/100 000, respectively in rural area. The crude mortality was 189.08/100 000(248.57/100 000 in males, 128.72/100 000 in females), and the age-standardized mortality according to China population and world population were 97.56/100 000 and 135.54/100 000 respectively. The cumulative mortality was 15.08%, and the cut mortality was 162.75/100 000. Age-specific mortality increased in age group 45-49 years(92.29/1000 000)and reached the peak in age group >=85 years(2 263.70/100 000). The mortality was higher in rural area(190.60/100 000)than in urban area(186.38/100 000). The leading cancers were lung cancer, colorectum cancer, thyroid cancer, stomach cancer and liver cancer, accounting for 58.64% of the total. Lung cancer, liver cancer, stomach cancer, colorectum cancer and esophagus cancer were the major cancers causing deaths, accounting for 70.72% of all the total. CONCLUSION: The leading cancers were lung cancer, colorectum cancer, thyroid cancer, stomach cancer and liver cancer in Zhejiang in 2014, close attention should be paid to thyroid cancer in women. The disease burden of malignant tumor is increasing,it is necessary for health department to take effective measures to reduce the disease burden caused by malignant tumor. PMID- 27188367 TI - [Trend and characteristics of fall in elderly adults based on data from national injury surveillance sentinel hospitals in Anhui province, 2006-2014]. AB - OBJECTIVE: To understand the incidence pattern of fall among older adults in Anhui province during 2006-2014, and provide scientific basis for intervention strategies and decision-making. METHODS: The incidence data of fall in elderly adults from 6 sentinel hospitals in 2 national injury surveillance areas in Anhui province between 2006 and 2014 were collected for this descriptive epidemiological analysis of the overall incidence trend, demographic characteristics, case distribution and clinical characteristics of fall cases in the elderly. RESULTS: The fall case number, the proportions of fall cases to injury cases and to overall fall cases in the elderly all increased from 2006 to 2014. The fall was the first cause of the elderly injury during the past 9 years. The sex ratio was 0.74 and the cases in males decreased with age. In both males and females, the cases in retirees and the jobless accounted for the highest proportions. The annual incidence peak was during August to October, and two daily incidence peaks were during 9 am-11 am and 16 pm-18 pm. The elderly falls mainly occurred at home(62.07%), and more females were affected than males(70.27% vs. 50.97%). Leisure activity and homework related falls accounted for 49.18% and 28.67% respectively, and more housework related falls occurred in females than in males. Contusion/abrasion was the first injury caused by fall in males(42.63%)and fracture was the first injury caused by fall in females(47.27%). Head was the first injury site in males(38.04%)and leg was the first injury site in females(29.29%). Most injuries caused by fall were mild(55.12%)and moderate(41.84%)in severity, but the proportions of moderate and severe cases increased gradually with age. CONCLUSION: Fall in the elderly has become a public health problem. It is necessary to take targeted prevention and control measures according to the gender and age distributions of the fall in the elderly. PMID- 27188368 TI - [Genomic characteristics of 2 strains of influenza A(H9N2)virus isolated from human infection cases in Anhui province]. AB - OBJECTIVE: To understand genomic characteristics of 2 strains of influenza A(H9N2)virus isolated from human infection cases in Anhui province in 2015. METHODS: Two human infection with H9N2 virus were confirmed by national influenza surveillance laboratory network in Anhui through viral isolation in April and September, 2015, respectively. The full genomic sequences of the two viral isolates were analyzed in this study by using molecular bioinformatics software Mega 6.0. RESULTS: Human infection with H9N2 virus was first reported in Anhui province. The analysis of genomic sequence showed that the HA and NA genes of the two H9N2 isolates belonged to A/Chicken/Shanghai/F/98(H9N2)-like lineage, and shared high identity with H9N2 virus circulating in poultry in 2013. The PB2 and MP genes belonged to the A/quail/Hong Kong/G1/97-like lineage, and shared high homology with H7N9, H10N8 or H6N2 viruses. The amino acid sequence alignment results showed that several mutations for human infection tropism presented in the two virus strains, including Q226L, H183N and E190T in HA; S31N in M2; 63-65 deletion in NA. In addition, the H9N2 influenza virus strains possessed the PSRSSR?GL motif in HA. Meanwhile several human-like signatures, including PA 100A, PA-356R and PA-409N were also found in the two virus strains. CONCLUSION: The H9N2 viruses isolated from human infection cases in Anhui province belonged to a reassortant virus originated from different lineage H9N2 avian influenza virus. The virus has possessed several human susceptibility locus. PMID- 27188369 TI - [Drug tolerance and PFGE molecular typing of Salmonella paratyphi A isolated in Dengfeng, Henan province, 2009-2015]. AB - OBJECTIVE: To investigate the drug tolerance and PFGE patterns of Salmonella(S.)paratyphi A strains isolated from sentinel hospitals in Dengfeng, Henan province, during 2009-2015. METHODS: Venous blood samples were collected from paratyphoid patients and cultured in double phase blood culture bottle. Suspicious strains were identified and used for Salomonella. O antigen and H1/2 phase flagellum-induced serum agglutination test with API20E biochemical systems and SSI Salmonella typing sera. According to Salmonella molecular typing and K-B drug susceptibility testing method published by PulseNet China bacterial infectious disease monitoring network and USA Clinical and Laboratory Standards Institute, we analyzed the drug susceptibility and PFGE molecule characteristics of S. paratyphi A strains isolated from the patients. RESULTS: A total of 126 strains of S. paratyphi A were isolated from 248 blood samples, the antigen modes of them were 1, 2, 12:a:-. The resistance rate of 126 strains of S. paratyphi A was 83.3% to ampicillin; 29.4% to ceftazidime, 31.2% to cefotaxime, 17.5% to cefepime; 62.6% to nalidixic acid; 19.3% to ciprofloxacin, 26.4% to norfloxacin; 22.8% to gentamicin, 47.9% to streptomycin; 19.2% to chloramphenicol, 24.2% to methicillin benzyl ammonium, 58.6% to compound sulfamethoxazole and 46.7% to tetracycline. The 126 strains of S. paratyphi A had different levels of resistance to 8 kinds of antibiotics, 109 strains were multidrug resistant(86.5%), 9 strains were resistant to 2-3 kinds of antibiotics(7.1%), 76 strains were resistant to 5-8 kinds of antibiotics(60.3%), 17 strains were resistant to 9-10 kinds of antibiotics(13.5%), 7 strains were resistant to 11-12 kinds of antibiotics(5.6%). The 126 strains of S. paratyphi A were divided into 14 molecular patterns by digestion with XbaIand pulsed field gel electrophoresis. The antibiotics resistance to third generation cephalosporin(CAZ, CTX), one generation and three generation of quinolones(NAL, CIP, NOR)and aminoglycosides antibiotics(STR)showed an upward trend. Each pattern contained 1-98 strains with similarity ranged from 64.10% to 100.00%. PTYA 1, 6, 9 and 10 were the main PFGE belt types. CONCLUSION: The drug resistance of clinical isolates of S. paratyphi A was serious in Dengfeng, Henan province, PFGE patterns showed a diversity, but predominant patterns could also be found. The PFGE patterns of some strains had clustering and were related with their antidrug spectrums. PMID- 27188370 TI - [Application of frailty index for comprehensive geriatric assessment in the elderly in China]. AB - OBJECTIVE: To discuss the suitability of frailty index for comprehensive geriatric assessment(FI-CGA)in the elderly in China, and evaluate the application of FI-CGA in China. METHODS: A comprehensive geriatric assessment was conducted among 118 old adults receiving health examination, and frailty index was calculated. Clinical frailty scale(CFS)was also used to evaluate the frail status of the old adults. The correlation between FI-CGA value and CFS level of the old adults was analyzed. RESULTS: The mean value of FI-CGA was 0.19 +/- 0.07, and the average level of CFS was 3.11 +/- 1.46. Women had higher mean value of FI-CGA and higher CFS level than men(FI-CGA= 0.20 +/- 0.02 for women, 0.19 +/- 0.07 for men; CFS =3.40 +/- 0.55 for women, 3.10 +/- 1.48 for men), but the differences had no significance(t=0.270, 0.452, P=0.788, 0.652). The FI-CGA value and CFS level increased with age(F=10.437, 5.651, P=0.000, 0.001); and there was a positive correlation between FI-CGA value and CFS level(r=0.615, P=0.000). CONCLUSION: FI CGA is an effective model for the quantitative evaluation of the frail status of the elderly, and can be used in the clinical practice of geriatric medicine. PMID- 27188371 TI - [Influence of hypothyroidism on pregnancy outcome and fetus during pregnancy]. AB - OBJECTIVE: To investigate the influence of hypothyroidism on pregnancy outcome and fetus in pregnant women. METHODS: A total of 4 286 pregnant women, who received prenatal examination in our hospital from January 2013 to October 2015, were selected as study subjects. The incidence of hypothyroidism and the influence on pregnancy outcomes and fetus were investigated. RESULTS: In 4 286 pregnant women surveyed, 209 hypothyroidism cases were detected(4.9%), including 85 clinical hypothyroidism cases and 124 subclinical hypothyroidism cases. In health group, the premature delivery rate was 1.0%, significantly lower than that in clinical hypothyroidism group(10.6%)and in subclinical hypothyroidism group(6.5%), the differences were significant(chi(2)= 38.884, P<0.001; chi(2)=17.722, P<0.001). In healthy group, the incidence of anemia was 3.8%, significantly lower than that in clinical hypothyroidism group(18.8%)and in subclinical hypothyroidism group(9.7%), the differences were significant(chi(2)=30.949, P<0.001; chi(2)=23.275, P<0.001). In health group, the incidence of low birth weight was 1.1%, significantly lower than that in clinical hypothyroidism group(14.1%)and in subclinical hypothyroidism group(4.8%), the differences were significant(chi(2)=50.593, P<0.001; chi(2)=15.637, P<0.001). In health group, the fetal distress incidence was 1.9%, significantly lower than that in clinical hypothyroidism group(10.6%)and in subclinical hypothyroidism group(5.6%), the differences were significant(chi(2)=19.257, P< 0.001; chi(2)=12.357, P<0.001). In health group, the fetal Apgar score(9.69 +/- 0.32)was significantly higher than those in clinical hypothyroidism group(9.25 +/- 0.45)and in subclinical hypothyroidism group(9.28 +/- 0.44), the differences were significant(t=8.823, P<0.001; t=15.175, P<0.001). CONCLUSION: Hypothyroidism during pregnancy has adverse influences on pregnancy outcome and fetus, and it is necessary to strengthen the hypothyroidism detection in pregnant women for the early treatment. PMID- 27188372 TI - [Relationship between N-nitrosodimethylamine and risk of digestive tract cancers: a Meta analysis based on cohort studies]. AB - OBJECTIVE: To analyze the relationship between N-nitrosodimethylamine(NDMA)and the risk of digestive tract cancers. METHODS: The papers about the relationship between NDMA and the risk of digestive tract cancers published from 1980 to 2012 were retrieved following databases: Chinese BioMedical Literature Database(CBM), the Chinese Journal Full-text Database(CNKI), Wanfang Database, PubMed and EBSCO. The fix and random effect model was used and statistical analyses were conducted by using RevMan 5.1 software. RESULTS: Thirteen papers were found, in which 7 about digestive tract cancers were used in this Meta analysis. The NDMA had significant positive effect on the incidence of digestive tract cancers(RR=1.12, 95% CI: 1.03-1.21). The relationship between NDMA and esophageal cancer was not significant(RR=1.18, 95%CI: 0.98-1.41)but NDMA could increase the risk of gastric cancer(RR=1.08, 95% CI: 1.00-1.18). For the subtypes of esophageal and gastric cancer, NDMA had positive relationship with esophageal squamous cell carcinoma(RR=1.72, 95% CI: 1.01-2.96), but had no significant relationship with esophageal adenocarcinoma, cardiac carcinoma and gastric adenocarcinoma. CONCLUSION: The population-based cohort studies have showed that the NDMA could significantly increase the risk of digestive tract cancers, but the effects differed with subtypes of esophageal and gastric cancer. However, it is necessary to collect more evidence due to the limited studies and obvious differences in the study design, sampling and exposure measurement of these cohort studies. PMID- 27188375 TI - [Application of PASS in sample size estimation of non-inferiority, equivalence and superiority design in clinical trials]. AB - The sample size of non-inferiority, equivalence and superiority design in clinical trial was estimated by using PASS 11 software. The result was compared with that by using SAS to evaluate the practicability and accuracy of PASS 11 software for the purpose of providing reference for sample size estimation in clinical trial design. PMID- 27188373 TI - [Influencing factors of type 2 diabetes mellitus in Chinese: a Meta-analysis]. AB - OBJECTIVE: To evaluate the influencing factors of type 2 diabetes mellitus in Chinese, and provide evidence for developing health promotion policy in the future. METHODS: Relevant studies published from January 1997 to May 2015 were retrieved from PubMed, Medline, EBSCO, Science Direct, CBM, CNKI, VIP, and Wanfang Database. Quality evaluation of the included literatures was conducted according to the inclusion and exclusion criteria, followed by data extraction and Meta-analysis with software RevMan 4.4.2. RESULTS: A total of 29 studies involving 92 970 subjects(11 150 cases and 81 820 controls)were included. The pooled OR and its 95% CI of each influencing factor were: overweight OR=1.66(1.49 1.85), abdominal obesity OR=1.98(1.31-3.01), family history of diabetes OR =3.13(2.52-3.87), smoking OR=1.46(1.24-1.72), drinking OR=1.19(1.09-1.29), hypertension OR=2.64(2.23-3.13), systolic blood pressure(SBP)OR=1.15(1.06-1.24), hyperlipoidemia OR=2.26(1.75-2.92), total cholesterol(TC)OR=1.87(1.14-3.08), triglyceride(TG)OR=1.73(1.23-2.44), history of coronary heart disease(CHD)OR=2.55(1.78-3.65), cerebrovascular accident(CVA)OR=2.21(1.62-3.02), dietary fat OR=0.52(0.27-0.99). The results of subgroup analysis identified 4 common influencing factors shared by the three subgroups, i.e. overweight, family history of diabetes, smoking and hypertension. CONCLUSION: Overweight, abdominal obesity, family history of diabetes, smoking, drinking, hypertension, SBP, TC, TG, history of CHD, history of CVA, and subtypes of dietary fat are the influencing factors for type 2 diabetes mellitus in Chinese. Among these factors, overweight in recent 20 years, family history of diabetes, smoking and hypertension are persistent factors. More attention should be paid to overweight and obesity. PMID- 27188376 TI - [Application of different death evaluation indicators for HIV/AIDS prevention and treatment]. AB - AIDS has gradually changed from a fatal disease to a manageable chronic disease since the advent of antiretroviral drugs. In 2003, China initiated a national free antiretroviral treatment program for people living with HIV/AIDS, several death evaluation indicators have been used to evaluate public health effect of the program. Death evaluation indicators used frequently in domestic and overseas include mortality, case fatality rate, excess mortality, standard mortality ratio, years of potential life lost, disability-adjusted life year and life expectancy. This paper summarizes the different death indicators applied in effectiveness evaluation of HIV/AIDS prevention and treatment, elaborates the application range and significance of these indicators and suggests the research in related life expectancy and burden of disease which have not been conducted in China. PMID- 27188374 TI - [Application of SAS macro to evaluated multiplicative and additive interaction in logistic and Cox regression in clinical practices]. AB - Conditional logistic regression analysis and unconditional logistic regression analysis are commonly used in case control study, but Cox proportional hazard model is often used in survival data analysis. Most literature only refer to main effect model, however, generalized linear model differs from general linear model, and the interaction was composed of multiplicative interaction and additive interaction. The former is only statistical significant, but the latter has biological significance. In this paper, macros was written by using SAS 9.4 and the contrast ratio, attributable proportion due to interaction and synergy index were calculated while calculating the items of logistic and Cox regression interactions, and the confidence intervals of Wald, delta and profile likelihood were used to evaluate additive interaction for the reference in big data analysis in clinical epidemiology and in analysis of genetic multiplicative and additive interactions. PMID- 27188377 TI - Outcomes of implementing the women's health assessment tool and clinical decision support toolkit. AB - AIM: To evaluate outcomes after implementing the women's health assessment tool (WHAT) and clinical decision support toolkit during annual well-women visits. METHODS: An observational project involved women aged 45-64 years attending one of three medical sites in Washington (WA, USA). Responses to the WHAT questionnaire and patients' health resource utilization prepost toolkit implementation were analyzed. RESULTS: A total of 110 women completed the WHAT questionnaire. Majority of women were postmenopausal (77.3%) and experienced depressive mood (63.6%), hot flashes (61.8%) or anxiety (60.9%) in the last 3 months. There was a 72.2% increase in the number of diagnoses made during the annual visit versus the previous 12 months. CONCLUSION: The WHAT/clinical decision support toolkit helped identify conditions relevant to mid-life women. PMID- 27188379 TI - ESR teleradiology survey: results. AB - With recent developments of teleradiology technology and services, it has become necessary to better evaluate its extent and use among different countries in Europe. With this goal in mind, the ESR launched two specific surveys intended to gather the current state of adoption and implementation of teleradiology in clinical practice. A special focus on differentiating between insourcing teleradiology services among partners of the same organisation and outsourcing to external services was an essential part of the design of these surveys. The first survey was addressed to 44 national societies of different countries in Europe, while the second survey was intended for all practicing radiologist ESR members. While the results of these surveys reported here may provide a wealth of information to better understand the trends in adoption of teleradiology in Europe, they only represent a snapshot at a certain point in time. The rapid development of telecommunication tools as well as a fundamental change in practice and healthcare economics will certainly influence these observations in the upcoming years. These data, however, will provide objective and relevant parameters for supporting the efforts of experts and policy makers in promoting appropriate criteria and guidelines for adequate use of teleradiology in clinical practice. Main Messages * Understand concepts and challenges of teleradiology * Provide insight into current trends and solutions for teleradiology * Compare differences in teleradiolgy strategies between countries in Europe * Establish a reference on statistical data of usage of teleradiology in Europe. PMID- 27188378 TI - Structural basis for haem piracy from host haemopexin by Haemophilus influenzae. AB - Haemophilus influenzae is an obligate human commensal/pathogen that requires haem for survival and can acquire it from several host haemoproteins, including haemopexin. The haem transport system from haem-haemopexin consists of HxuC, a haem receptor, and the two-partner-secretion system HxuB/HxuA. HxuA, which is exposed at the cell surface, is strictly required for haem acquisition from haemopexin. HxuA forms complexes with haem-haemopexin, leading to haem release and its capture by HxuC. The key question is how HxuA liberates haem from haemopexin. Here, we solve crystal structures of HxuA alone, and HxuA in complex with the N-terminal domain of haemopexin. A rational basis for the release of haem from haem-haemopexin is derived from both in vivo and in vitro studies. HxuA acts as a wedge that destabilizes the two-domains structure of haemopexin with a mobile loop on HxuA that favours haem ejection by redirecting key residues in the haem-binding pocket of haemopexin. PMID- 27188380 TI - Spectrum of early lung cancer presentation in low-dose screening CT: a pictorial review. AB - The typical presentation of early stage lung cancers on low-dose CT screening are non-calcified pulmonary nodules. However, there is a wide spectrum of unusual focal abnormalities that can be early presentations of lung cancer. These abnormalities include, for example, cancers associated with 'cystic airspaces' or scar-like cancers. The detection of lung cancer with low-dose CT can be affected by the absence of intravenous contrast medium. As a consequence, endobronchial and central lesions can be difficult to recognize, raising the potential for missed cancers. Focal lesions arising within pre-existing lung disease, such as lung fibrosis or apical scars, can also be early lung cancer manifestations and deserve particular consideration as recognition of these lesions may be hindered by the underlying disease. Furthermore, the unpredictable growth rate of lung cancer, which ranges from indolent to aggressive cancers, necessitates attention to the wide spectrum of progression in lung cancer appearance on serial low-dose CT scans. In this pictorial review we discuss the spectrum of early lung cancer presentation in low-dose CT screening, highlighting typical as well as unusual radiological features and the varied growth rates of early lung cancer. Teaching Points * There is a wide spectrum of early presentations of lung cancer on LDCT. * Low radiation dose and the absence of contrast medium injection can affect lung cancer detection. * Lung cancer growth shows various behaviours, ranging from indolent to aggressive cancers. * Familiarity with LDCT technique can improve CT screening effectiveness and avoid missed diagnosis. PMID- 27188381 TI - Bench-to-bedside translation of stem cell therapies: where are we now and where are we going? PMID- 27188382 TI - Brain arteriovenous malformations. AB - An arteriovenous malformation is a tangle of dysplastic vessels (nidus) fed by arteries and drained by veins without intervening capillaries, forming a high flow, low-resistance shunt between the arterial and venous systems. Arteriovenous malformations in the brain have a low estimated prevalence but are an important cause of intracerebral haemorrhage in young adults. For previously unruptured malformations, bleeding rates are approximately 1% per year. Once ruptured, the subsequent risk increases fivefold, depending on associated aneurysms, deep locations, deep drainage and increasing age. Recent findings from novel animal models and genetic studies suggest that arteriovenous malformations, which were long considered congenital, arise from aberrant vasculogenesis, genetic mutations and/or angiogenesis after injury. The phenotypical characteristics of arteriovenous malformations differ among age groups, with fistulous lesions in children and nidal lesions in adults. Diagnosis mainly involves imaging techniques, including CT, MRI and angiography. Management includes observation, microsurgical resection, endovascular embolization and stereotactic radiosurgery, alone or in any combination. There is little consensus on how to manage patients with unruptured malformations; recent studies have shown that patients managed medically fared better than those with intervention at short-term follow-up. By contrast, interventional treatment is preferred following a ruptured malformation to prevent rehaemorrhage. Management continues to evolve as new mechanistic discoveries and reliable animal models raise the possibility of developing drugs that might prevent the formation of arteriovenous malformations, induce obliteration and/or stabilize vessels to reduce rupture risk. For an illustrated summary of this Primer, visit: http://go.nature.com/TMoAdn. PMID- 27188383 TI - Two parameters reflect lipid-driven inflammatory state in acute coronary syndrome: atherogenic index of plasma, neutrophil-lymphocyte ratio. AB - BACKGROUND: Atherosclerosis is a systemic, lipid-driven immune-inflammatory disease. METHODS: We retrospectively reviewed institutional electronic medical records to seek chest pain patients who were suspicious of acute coronary syndrome (ACS) between January 2011 and December 2013. All the patients were identified by undergoing coronary angiography. On admission white blood cell and its subtypes were measured as part of the automated complete blood count and fasting venous blood samples were obtained and analyzed for lipids profiles used automated analysis. RESULTS: A total of 376 consecutive patients with ACS were investigated. In the same period, 378 patients admitted with chest pain suspicious of ACS were also included in this study for control. Blood glucose, serum creatinine, white blood cell, neutrophil and monocyte were insignificantly higher in the ACS group. ACS group had higher total cholesterol and lower high density lipid-cholesterol. However, triglyceride and low density lipid cholesterol were similar between ACS and control groups. Atherogenic index of plasma (AIP) was significantly higher in ACS group compared to control group (p = 0.029). Similarly, ACS group had higher neutrophil-lymphocyte ratio (NLR) than those in control group. In the subgroups, the NLR were significantly higher in the STEMI group (p < 0.001). However, AIP were similar between the three subgroups (p = 0.748). CONCLUSIONS: Our data firstly investigated the lipid driven inflammatory state in acute coronary syndrome through two easily feasible parameters. There suggest that there are higher AIP and NLR in the ACS patients. Moreover, ACS subgroups are all lipid-driven states, but inflammation levels are different in the entity ACS subgroups. PMID- 27188384 TI - Is there an association between subclinical hypothyroidism and preterm uterine contractions? A prospective observational study. AB - OBJECTIVE: To investigate the association between subclinical hypothyroidism and preterm contractions. METHODS: Prospective observational study among women at 23 + 0/7 and 34 + 6/7 weeks of gestation, with no known thyroid function abnormality, and preterm uterine contractions (PTC). All patients underwent laboratory evaluation of Thyroid Stimulating Hormone (TSH) and Free Thyroxin (FT4). Patients with and without PTC were compared. RESULTS: No association was found between PTC and subclinical hypothyroidism. Rate of spontaneous preterm delivery (PTD) was comparable between women with abnormal and normal thyroid function tests. Excluding indicated PTD, patients in the study group had a higher rate of spontaneous PTD (24.7% versus 9.6%, p = 0.03). Patients with past PTD and preterm contractions had higher rates of hypothyroxinemia compared with patients without past PTD (54.6% versus 19.0% and 31.2%, p = 0.001), and patients with past PTD (regardless of the presence or absence of PTC) had higher rate of subclinical hypothyroidism compared with patients with PTC and without PTD (59.1% and 66.7% versus 31.6%, p = 0.017). CONCLUSIONS: No association was found between PTC and subclinical hypothyroidism in the entire cohort, except for patients with preterm contractions and a history of past PTD. This specific group of patients might benefit from thyroid function evaluation. PMID- 27188385 TI - Adolescent idiopathic scoliosis. AB - Adolescent idiopathic scoliosis (AIS) is the most common form of structural spinal deformities that have a radiological lateral Cobb angle - a measure of spinal curvature - of >=10( degrees ). AIS affects between 1% and 4% of adolescents in the early stages of puberty and is more common in young women than in young men. The condition occurs in otherwise healthy individuals and currently has no recognizable cause. In the past few decades, considerable progress has been made towards understanding the clinical patterns and the three-dimensional pathoanatomy of AIS. Advances in biomechanics and technology and their clinical application, supported by limited evidence-based research, have led to improvements in the safety and outcomes of surgical and non-surgical treatments. However, the definite aetiology and aetiopathogenetic mechanisms that underlie AIS are still unclear. Thus, at present, both the prevention of AIS and the treatment of its direct underlying cause are not possible. PMID- 27188388 TI - ZnO-(Cu/Ag)TCNQ heterostructure network over flexible platform for enhanced cold cathode application. AB - Multistage field emitters consisting of organic/inorganic hybrid nanostructures with branched geometry are designed via a two-step protocol: a simple wet chemical method followed by a vapor-solid-phase technique. (Cu/Ag)TCNQ (copper/silver-7,7,8,8-tetracyanoquinodimethane) nanowires (NWs) were grown hierarchically on zinc oxide (ZnO) nanorods (NRs) to form ZnO-(Cu/Ag)TCNQ heterostructure assemblies. By monitoring the metallic Cu and Ag coating thickness on ZnO NRs, precise control over the morphology and orientations of the secondary organic NWs is achieved. In-depth analysis of electron field emission (FE) behavior of the ZnO-(Cu/Ag)TCNQ-based hierarchy suggests highest emission performance with low turn-on as well as threshold fields of 1.15 and 3.75 V MUm( 1) respectively from the morphology-optimized hierarchy. Beneficial orientation of the branched organic NWs ensures sequential electric field enhancement in the consecutive stem and branches whereas its low work function eases electron emission; these aspects combined together render an overall enhancement in the emission behavior of the hybrid system. As compared to individual building units, the heterostructures show improved field electron emission. Additionally, successful construction of this novel hybrid over a fabric platform displays great potential in opening up new pathways in the highly-anticipated field of flexible electronics. PMID- 27188389 TI - Nonrecurrent inferior laryngeal nerves and anatomical findings during thyroid surgery: report of three cases. AB - A nonrecurrent inferior laryngeal nerve (NRILN) is found more frequently on the right side than on the left, and it is closely associated with an aberrant right subclavian artery. The presence of the aberrant right subclavian artery on preoperative computed tomography (CT) scan suggests NRILN; however, different types of branching locations and pathways exist. Here, we report three NRILN cases with different pathways where the vagus nerve arises more medial than usual and a review of the literature. Case 1: A 30-year-old Japanese female presented with papillary thyroid carcinoma. Preoperative CT scan revealed an aberrant right subclavian artery, and an operation was performed under suspicion of NRILN. During the operation, the vagus nerve was found to arise more medially than usual and two NRILNs originated from it at the level of the cricoid cartilage and at a more caudal position; the two NRILNs were preserved. Case 2: A 33-year-old Japanese female with a thyroid nodule of increased size underwent surgery. Preoperative CT scan revealed an aberrant right subclavian artery, which suggested NRILN. During the operation, the vagus nerve was identified to run more medially than usual and NRILN was found to originate at the level of the cricoid cartilage; NRILN was preserved. Case 3: A 78-year-old Japanese female underwent an operation with a diagnosis of papillary thyroid carcinoma. Preoperative CT scan showed an aberrant right subclavian artery. During the operation, NRILN was found to originate from the vagus nerve at the level of the lower pole of the thyroid gland, and the vagus nerve ran medial to the common carotid artery at the caudal level. PMID- 27188386 TI - Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. AB - Stem cell-based in vitro test systems can recapitulate specific phases of human development. In the UKK test system, human pluripotent stem cells (hPSCs) randomly differentiate into cells of the three germ layers and their derivatives. In the UKN1 test system, hPSCs differentiate into early neural precursor cells. During the normal differentiation period (14 days) of the UKK system, 570 genes [849 probe sets (PSs)] were regulated >fivefold; in the UKN1 system (6 days), 879 genes (1238 PSs) were regulated. We refer to these genes as 'developmental genes'. In the present study, we used genome-wide expression data of 12 test substances in the UKK and UKN1 test systems to understand the basic principles of how chemicals interfere with the spontaneous transcriptional development in both test systems. The set of test compounds included six histone deacetylase inhibitors (HDACis), six mercury-containing compounds ('mercurials') and thalidomide. All compounds were tested at the maximum non-cytotoxic concentration, while valproic acid and thalidomide were additionally tested over a wide range of concentrations. In total, 242 genes (252 PSs) in the UKK test system and 793 genes (1092 PSs) in the UKN1 test system were deregulated by the 12 test compounds. We identified sets of 'diagnostic genes' appropriate for the identification of the influence of HDACis or mercurials. Test compounds that interfered with the expression of developmental genes usually antagonized their spontaneous development, meaning that up-regulated developmental genes were suppressed and developmental genes whose expression normally decreases were induced. The fraction of compromised developmental genes varied widely between the test compounds, and it reached up to 60 %. To quantitatively describe disturbed development on a genome-wide basis, we recommend a concept of two indices, 'developmental potency' (D p) and 'developmental index' (D i), whereby D p is the fraction of all developmental genes that are up- or down-regulated by a test compound, and D i is the ratio of overrepresentation of developmental genes among all genes deregulated by a test compound. The use of D i makes hazard identification more sensitive because some compounds compromise the expression of only a relatively small number of genes but have a high propensity to deregulate developmental genes specifically, resulting in a low D p but a high D i. In conclusion, the concept based on the indices D p and D i offers the possibility to quantitatively express the propensity of test compounds to interfere with normal development. PMID- 27188390 TI - Combinatorial Study of a Novel Poly (ADP-ribose) Polymerase Inhibitor and an HDAC Inhibitor, SAHA, in Leukemic Cell Lines. AB - BACKGROUND: Cancer is a multifactorial disease, which makes it difficult to cure. Since more than one defective cellular component is often involved during oncogenesis, combination therapy is gaining prominence in the field of cancer therapeutics. OBJECTIVE: The purpose of this study was to investigate the combinatorial effects of a novel PARP inhibitor, P10, and HDAC inhibitor, SAHA, in leukemic cells. METHODS: Combinatorial effects of P10 and SAHA were tested using propidium iodide staining in different leukemic cells. Further, flowcytometry-based assays such as calcein-AM/ethidium homodimer staining, annexin-FITC/PI staining, and JC-1 staining were carried out to elucidate the mechanism of cell death. In addition, cell-cycle analysis, immunocytochemistry studies, and western blotting analysis were conducted to check the combinatorial effect in Nalm6 cells. RESULTS: Propidium iodide staining showed that P10 in combination with SAHA induced cell death in Nalm6 cells, in which PARP expression and activity is high with a combination index of <0.2. Annexin-FITC/PI staining, JC-1 staining, and other biochemical assays revealed that P10 in combination with SAHA induced apoptosis by causing a change in mitochondrial membrane potential in >65 % cells. Importantly, combinatorial treatment induced S phase arrest in 40-45 % cells due to DNA damage and plausible replicative stress. Finally, we demonstrated that treatment with P10 led to DNA strand breaks, which were further potentiated by SAHA (p < 0.01), leading to activation of apoptosis and increased cell death in PARP-positive leukemic cells. CONCLUSIONS: Our study reveals that coadministration of PARP inhibitor with SAHA could be used as a combination therapy against leukemic cells that possess high levels of intrinsic PARP activity. PMID- 27188387 TI - Auto-induction mechanism of aryl hydrocarbon receptor 2 (AHR2) gene by TCDD activated AHR1 and AHR2 in the red seabream (Pagrus major). AB - The toxic effects of dioxins and related compounds (DRCs) are mediated by the aryl hydrocarbon receptor (AHR). Our previous study identified AHR1 and AHR2 genes from the red seabream (Pagrus major). Moreover, we found that AHR2 mRNA levels were notably elevated by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure in the early life stage of red seabream embryos, while AHR1 mRNA level was not altered. In this study, to investigate the regulatory mechanism of these AHR transcripts, we cloned and characterized 5'-flanking regions of AHR1 and AHR2 genes. Both of the 5'-flanking regions in these AHR genes contained three potential xenobiotic-responsive elements (XREs). To assess whether the 5' flanking region is transactivated by rsAHR1 and rsAHR2 proteins, we measured the transactivation potency of the luciferase reporter plasmids containing the 5' flanking regions by AHR1 and AHR2 proteins that were transiently co-expressed in COS-7. Only reporter plasmid (pGL4-rsAHR2-3XREs) that contained three putative XRE sites in the 5'-flanking region of AHR2 gene showed a clear TCDD dose dependent transactivation by AHR1 and AHR2 proteins. TCDD-EC50 values for the rsAHR2-derived XRE transactivation were 1.3 and 1.4 nM for AHR1 and AHR2, respectively. These results suggest that the putative XREs of AHR2 gene have a function for AHR1- and AHR2-mediated transactivation, supporting our in ovo observation of an induction of AHR2 mRNA levels by TCDD exposure. Mutations in XREs of AHR2 gene led to a decrease in luciferase induction. Electrophoretic mobility shift assay showed that XRE1, the closest XRE from the start codon in AHR2 gene, is mainly responsible for the binding with TCDD-activated AHR. This suggests that TCDD-activated AHR1 and AHR2 up-regulate the AHR2 mRNA levels and this auto-induced AHR2 may amplify the signal transduction of its downstream targets including CYP1A in the red seabream. PMID- 27188392 TI - Erratum to: The transcription factor MITF is a critical regulator of GPNMB expression in dendritic cells. PMID- 27188393 TI - Icosahedral boron clusters: a perfect tool for the enhancement of polymer features. AB - Boron clusters and organic molecules display manifestly different electronic, physical, chemical and geometrical characteristics. These differences highlight the complementarity of organic synthons and boron clusters, and therefore the feasibility of producing hybrid polymers incorporating both types of fragments. This review focuses on the development of hybrid organic-inorganic pi conjugated, silane, siloxane and coordination polymers containing icosahedral boron clusters in the last few decades, which have received considerable academic and technological interest due to the combination of the electronic, optical and thermal properties of traditional inorganic materials with many of the desirable properties of organic plastics, including mechanical flexibility and low production costs. PMID- 27188391 TI - Effects of Fatty Acid Synthase Inhibition by Orlistat on Proliferation of Endometrial Cancer Cell Lines. AB - OBJECTIVE: Fatty acid synthase (FAS) is a key lipogenic enzyme that is highly expressed in endometrial cancer. Orlistat is a weight loss medication that has been shown to be a potent inhibitor of FAS. The goal of this study was to evaluate the anti-tumorigenic potential of orlistat in endometrial cancer cell lines. METHODS: The endometrial cancer cell lines ECC-1 and KLE were used. Cell proliferation was assessed by MTT assay after treatment with orlistat. Cell cycle progression was evaluated by Cellometer and apoptosis was assessed using the Annexin V assay. Reactive oxygen species (ROS) was measured using the DCFH-DA assay. Western immunoblotting was performed to determine changes in FAS, cellular stress, cell cycle progression, and the AMPK/mTOR pathways. RESULTS: Orlistat inhibited cell proliferation by 61 % in ECC-1 cells and 57 % in KLE cells at a dose of 500 MUM. Treatment with orlistat at this concentration resulted in G1 arrest (p < 0.05) but did not affect apoptosis. Orlistat increased ROS and induced the expression of BIP (1.28-fold in ECC-1 compared to control, p < 0.05; 1.92-fold in KLE, p < 0.05) and PERK (2.25-fold in ECC-1, 1.4-fold in KLE, p < 0.05). Western immunoblot analysis demonstrated that orlistat decreased expression of important proteins in fatty acid metabolism including FAS (67 % in ECC-1, 15 % in KLE), acetyl-CoA carboxylase (40 % in ECC-1, 35 % in KLE), and carnitine palmitoyltransferase 1A (CPT1A) (65 % in ECC-1, 25 % in KLE) in a dose dependent manner. In addition, orlistat at a dose of 500 MUM increased expression of phosphorylated-AMPK (1.9-fold in ECC-1, p < 0.01; 1.5-fold in KLE, p < 0.05) and decreased expression of phosphorylated-Akt (25 % in ECC-1, p < 0.05; 37 % in KLE, p < 0.05) and phosphorylated-S6 (68 % in ECC-1, 56 % in KLE). CONCLUSIONS: Orlistat inhibits cell growth in endometrial cancer cell lines through inhibition of fatty acid metabolism, induction of cell cycle G1 arrest, activation of AMPK and inhibition of the mTOR pathway. Given that patients with endometrial cancer have high rates of obesity, orlistat should be further investigated as a novel strategy for endometrial cancer treatment. PMID- 27188394 TI - Drug loading and delivery using nanofibers scaffolds. AB - In recent times, notable advancement has been made in the field of electrospinning for the fabrication of numerous types of nanofiber scaffolds. Due to the ultrathin fiber diameter, electrospun nanofiber scaffolds are considered to be an operational delivery system for biomolecules, genes, as well as drugs due to the high specific surface area and stereological porous structure. Here, we introduce some of methods for the integration of drugs and biomolecules within electrospun nanofiber scaffolds, such as blending, surface modification, coaxial process, and emulsion methods. Then, we describe some important biomedical applications of nanofibers in drug delivery systems along with their suitable examples in transdermal systems and wound dressings, cancer therapy, growth factor delivery, nucleic acid delivery, and stem cell delivery. PMID- 27188395 TI - Noninvasive Predictors of Malignant Arrhythmias. AB - BACKGROUND: Prediction and potential prevention of sudden cardiac death (SCD) due to malignant ventricular arrhythmia (MVA) represent an obvious unmet medical need. We estimated the prognostic relevance of numerous biomarkers associated with future MVA development in patients with coronary artery disease (CAD) over 2 years of follow-up. METHODS: Patients with stable documented CAD (n = 97) with a mean age of 61 +/- 10 years were prospectively enrolled in a single-center observational cohort study. Heart failure was diagnosed in 68% of the patients (NYHA class II-III). The mean left ventricular ejection fraction (LVEF) was 50 +/ 13%, while 20% of patients had LVEF <=35%. Sixty-two patients underwent myocardial revascularization during the follow-up (mean 25 +/- 11 months). Clinical characteristics (age, gender, diabetes, history of coronary disease and arrhythmias, prior interventions and antecedent medications), noninvasive electrophysiological markers [microvolt T-wave alterations, signal-averaged electrocardiography, QT interval duration and alteration, and heart rate turbulence (HRT) and HR variability], laboratory indices [serum creatinine and creatinine clearance, brain natriuretic peptide (BNP), NT-proBNP, and C-reactive protein and troponin T levels] were assessed with regard to the MVA prognosis. RESULTS: MVA was diagnosed in 11 patients during the prospective follow-up. Prior percutaneous coronary intervention (p < 0.05), MVA or syncope (p < 0.05), on-pump coronary artery bypass grafting during follow-up (p < 0.01), LVEF <=47% (p < 0.01), a left atrium size >=4.7 cm (p < 0.05), left atrium index (p = 0.01), filtered QRS duration (p < 0.05), abnormal HRT (x03C7;2 = 6.2, p = 0.01) or turbulence slope (x03C7;2 = 9.5, p < 0.01), BNP >=158 pg/ml (p < 0.01) and NT proBNP >=787 pg/ml (x03C7;2 = 4.4, p < 0.05) were significantly associated with MVA risk by univariate analysis. However, only prior MVA or syncope [odds ratio (OR) 11.1; 95% confidence interval (CI) 2.8-44.4; p < 0.01], abnormal HRT (x041E;R 13.6; 95% CI 2.8-66.1; p < 0.01) and plasma BNP (x041E;R 14.3; 95% CI 3.2-65.0; p < 0.01) remained independent predictors of MVA occurrence by multivariate Cox regression analysis. CONCLUSION: Prior syncope or MVA, HRT and elevated plasma BNP were independent MVA predictors, advocating for the prospective screening of high-risk CAD patients for potential SCD awareness. PMID- 27188398 TI - Dietary indispensable amino acids profile affects protein utilization and growth of Senegalese sole larvae. AB - In diet formulation for fish, it is critical to assure that all the indispensable amino acids (IAA) are available in the right quantities and ratios. This will allow minimizing dietary AA imbalances that will result in unavoidable AA losses for energy dissipation rather than for protein synthesis and growth. The supplementation with crystalline amino acids (CAA) is a possible solution to correct the dietary amino acid (AA) profile that has shown positive results for larvae of some fish species. This study tested the effect of supplementing a practical microdiet with encapsulated CAA as to balance the dietary IAA profile and to improve the capacity of Senegalese sole larvae to utilize AA and maximize growth potential. Larvae were reared at 19 degrees C under a co-feeding regime from mouth opening. Two microdiets were formulated and processed as to have as much as possible the same ingredients and proximate composition. The control diet (CTRL) formulation was based on commonly used protein sources. A balanced diet (BAL) was formulated as to meet the ideal IAA profile defined for Senegalese sole: the dietary AA profile was corrected by replacing 4 % of encapsulated protein hydrolysate by CAA. The in vivo method of controlled tube-feeding was used to assess the effect on the larvae capacity to utilize protein, during key developmental stages. Growth was monitored until 51 DAH. The supplementation of microdiets with CAA in order to balance the dietary AA had a positive short-term effect on the Senegalese sole larvae capacity to retain protein. However, that did not translate into increased growth. On the contrary, larvae fed a more imbalanced (CTRL group) diet attained a better performance. Further studies are needed to ascertain whether this was due to an effect on the voluntary feed intake as a compensatory response to the dietary IAA imbalance in the CTRL diet or due to the higher content of tryptophan in the BAL diet. PMID- 27188396 TI - RNA motif search with data-driven element ordering. AB - BACKGROUND: In this paper, we study the problem of RNA motif search in long genomic sequences. This approach uses a combination of sequence and structure constraints to uncover new distant homologs of known functional RNAs. The problem is NP-hard and is traditionally solved by backtracking algorithms. RESULTS: We have designed a new algorithm for RNA motif search and implemented a new motif search tool RNArobo. The tool enhances the RNAbob descriptor language, allowing insertions in helices, which enables better characterization of ribozymes and aptamers. A typical RNA motif consists of multiple elements and the running time of the algorithm is highly dependent on their ordering. By approaching the element ordering problem in a principled way, we demonstrate more than 100-fold speedup of the search for complex motifs compared to previously published tools. CONCLUSIONS: We have developed a new method for RNA motif search that allows for a significant speedup of the search of complex motifs that include pseudoknots. Such speed improvements are crucial at a time when the rate of DNA sequencing outpaces growth in computing. RNArobo is available at http://compbio.fmph.uniba.sk/rnarobo . PMID- 27188399 TI - Pancreatic Lesion: Malignancy or Abscess? AB - BACKGROUND: Pancreatic abscesses are rare. They may be seen in patients with pancreatic inflammation or pancreatitis. Patients with pancreatic abscesses may have abdominal pain, fever, chills, and nausea/vomiting or an inability to eat. Presentation with alternate symptomatology is extremely unusual. CASE REPORT: A 67-year-old Asian male presented with painless, afebrile obstructive jaundice and a CA 19-9 of 1732 IU. He was found to have a 3.1*2.4 cm low-density lesion in the head of the pancreas and the right lobe of the liver, suggesting malignancy. Surgical management was considered, however additional diagnostic workup, including an endoscopic retrograde cholangiopancreatography (ERCP), was performed to complete staging of the presumed mass. A smooth, 3-cm-long, tapering stricture was found it the common bile duct. It was stented from the common hepatic duct to the duodenum. Subsequent endoscopic ultrasound (EUS) evaluation of the pancreatic head lesion revealed a drainable fluid collection that was aspirated and found to contain pyogenic material on pathology. The patient's symptoms resolved, and he was subsequently managed conservatively. A repeat ERCP confirmed complete resolution of the previously visualized cystic lesion. Interestingly, laboratory values showed concomitant normalization of CA 19-9 to 40 IU. CONCLUSIONS: EUS guided biopsy is not widely regarded as a required step before surgery, in the management of patients with pancreatic masses. It is generally reserved for determination of resectability or staging, and only utilized when clinically indicated. However, this practice may be associated with an inherently significant risk of misdiagnosis and subsequent unnecessary surgery, as illustrated by this case. Malignancy was initially suspected in our patient and surgical resection was recommended. Endoscopic measures were only pursued to complete staging. We propose that EUS-guided biopsy may be a crucial diagnostic step in the management algorithm of pancreatic lesions in selected patients. In addition, we encourage consideration of nonmalignant pancreatic collections in the differential diagnosis of pancreatic masses, especially when present in patients with diabetes mellitus. PMID- 27188401 TI - Synthesis of 9,10-Phenanthrenes via Palladium-Catalyzed Aryne Annulation by o Halostyrenes and Formal Synthesis of (+/-)-Tylophorine. AB - A novel palladium-catalyzed annulation reaction of in situ generated arynes and o halostyrenes has been developed. This methodology affords moderate to excellent yields of substituted phenanthrenes and is tolerant of a variety of functional groups such as nitrile, ester, amide, and ketone. This annulation chemistry has been successfully applied to the formal total synthesis of a biologically active alkaloid (+/-)-tylophorine. PMID- 27188402 TI - Silicon quantum dot sensors for an explosive taggant, 2,3-dimethyl-2,3 dinitrobutane (DMNB). AB - Silicon quantum dots obtained by the reaction of magnesium silicide with ethylenediamine dihydrochloride were utilized to investigate the sensing mechanism and sensitivity for DMNB detection applications. Sensing DMNB provided us with evidence that Si QDs with a higher lying conduction band have better sensitivity compared to CdSe QDs. PMID- 27188400 TI - Structural effects of naphthalimide-based fluorescent sensor for hydrogen sulfide and imaging in live zebrafish. AB - Hydrogen sulfide (H2S) is an important biological messenger, but few biologically compatible methods are available for its detection in aqueous solution. Herein, we report a highly water-soluble naphthalimide-based fluorescent probe (L1), which is a highly versatile building unit that absorbs and emits at long wavelengths and is selective for hydrogen sulfide over cysteine, glutathione, and other reactive sulfur, nitrogen, and oxygen species in aqueous solution. We describe turn-on fluorescent probes based on azide group reduction on the fluorogenic 'naphthalene' moiety to fluorescent amines and intracellular hydrogen sulfide detection without the use of an organic solvent. L1 and L2 were synthetically modified to functional groups with comparable solubility on the N imide site, showing a marked change in turn-on fluorescent intensity in response to hydrogen sulfide in both PBS buffer and living cells. The probes were readily employed to assess intracellular hydrogen sulfide level changes by imaging endogenous hydrogen sulfide signal in RAW264.7 cells incubated with L1 and L2. Expanding the use of L1 to complex and heterogeneous biological settings, we successfully visualized hydrogen sulfide detection in the yolk, brain and spinal cord of living zebrafish embryos, thereby providing a powerful approach for live imaging for investigating chemical signaling in complex multicellular systems. PMID- 27188403 TI - A TIPS-TPDO-tetraCN-Based n-Type Organic Field-Effect Transistor with a Cross linked PMMA Polymer Gate Dielectric. AB - Recent improvement in the performance of the n-type organic semiconductors as well as thin gate dielectrics based on cross-linked polymers offers new opportunities to develop high-performance low-voltage n-type OFETs suitable for organic complementary circuits. Using TIPS-tetracyanotriphenodioxazine (TIPS-TPDO tetraCN) and cross-linked poly(methyl methacrylate) (c-PMMA), respectively as n type organic semiconductor and gate dielectric, linear regime field-effect mobility (1.8 +/- 0.2) * 10(-2) cm(2) V(-1)s(-1), small spatial standard deviation of threshold voltage (~0.1 V), and operating voltage less than 3 V are attainable with the same device structure and contact materials used commonly for p-type OFETs. Through comparative static and dynamic characterizations of c-PMMA and PMMA gate dielectrics, it is shown that both smaller thickness and larger relative permittivity of c-PMMA contributes to reduced operating voltage. Furthermore, negligible hysteresis brings evidence to small trap states in the semiconductor near gate dielectric of the n-type OFETs with c-PMMA. The use of TIPS-TPDO-tetraCN and c-PMMA is fully compatible with polyethylene terephthalate substrate, giving promise to various flexible applications. PMID- 27188404 TI - Deaths, late deaths, and role of infecting dose in Ebola virus disease in Sierra Leone: retrospective cohort study. AB - OBJECTIVES: To assess the frequency of fatal recrudescence from Ebola virus disease after discharge from treatment centres, and explore the influence of infecting dose on case fatality rates. DESIGN: Retrospective cohort study. SETTING: Western Area, Sierra Leone. PARTICIPANTS: 151 survivors treated for Ebola virus disease at the Kerry Town treatment centre and discharged. Survivors were followed up for a vital status check at four to nine months after discharge, and again at six to 13 months after discharge. Verbal autopsies were conducted for four survivors who had died since discharge (that is, late deaths). Survivors still living in Western Area were interviewed together with their household members. Exposure level to Ebola virus disease was ascertained as a proxy of infecting dose, including for those who died. MAIN OUTCOME MEASURES: Risks and causes of late death; case fatality rates; odds ratios of death from Ebola virus disease by age, sex, exposure level, date, occupation, and household risk factors. RESULTS: Follow-up information was obtained on all 151 survivors of Ebola virus disease, a mean of 10 months after discharge. Four deaths occurred after discharge, all within six weeks: two probably due to late complications, one to prior tuberculosis, and only one after apparent full recovery, giving a maximum estimate of recrudescence leading to death of 0.7%. In these households, 395 people were reported to have had Ebola virus disease, of whom 227 died. A further 53 people fulfilled the case definition for probable disease, of whom 11 died. Therefore, the case fatality rate was 57.5% (227/395) for reported Ebola virus disease, or 53.1% (238/448) including probable disease. Case fatality rates were higher in children aged under 2 years and adults older than 30 years, in larger households, and in infections occurring earlier in the epidemic in Sierra Leone. There was no consistent trend of case fatality rate with exposure level, although increasing exposure increased the risk of Ebola virus disease. CONCLUSIONS: In this study of survivors in Western Area, Sierra Leone, late recrudescence of severe Ebola virus disease appears to be rare. There was no evidence for an effect of infecting dose (as measured by exposure level) on the severity of disease. PMID- 27188405 TI - Nerve Stimulation Enhances Task-Oriented Training in Chronic, Severe Motor Deficit After Stroke: A Randomized Trial. AB - BACKGROUND AND PURPOSE: A sensory-based intervention called peripheral nerve stimulation can enhance outcomes of motor training for stroke survivors with mild to-moderate hemiparesis. Further research is needed to establish whether this paired intervention can have benefit in cases of severe impairment (almost no active movement). METHODS: Subjects with chronic, severe poststroke hemiparesis (n=36) were randomized to receive 10 daily sessions of either active or sham stimulation (2 hours) immediately preceding intensive task-oriented training (4 hours). Upper extremity movement function was assessed using Fugl-Meyer Assessment (primary outcome measure), Wolf Motor Function Test, and Action Research Arm Test at baseline, immediately post intervention and at 1-month follow-up. RESULTS: Statistically significant difference between groups favored the active stimulation group on Fugl-Meyer at postintervention (95% confidence interval [CI], 1.1-6.9; P=0.008) and 1-month follow-up (95% CI, 0.6-8.3; P=0.025), Wolf Motor Function Test at postintervention (95% CI, -0.21 to -0.02; P=0.020), and Action Research Arm Test at postintervention (95% CI, 0.8-7.3; P=0.015) and 1-month follow-up (95% CI, 0.6-8.4; P=0.025). Only the active stimulation condition was associated with (1) statistically significant within group benefit on all outcomes at 1-month follow-up and (2) improvement exceeding minimal detectable change, as well as minimal clinically significant difference, on >=1 outcomes at >=1 time points after intervention. CONCLUSIONS: After stroke, active peripheral nerve stimulation paired with intensive task-oriented training can effect significant improvement in severely impaired upper extremity movement function. Further confirmatory studies that consider a larger group, as well as longer follow-up, are needed. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02633215. PMID- 27188406 TI - Poor Outcome of Stroke Patients With Atrial Fibrillation in the Presence of Coexisting Spontaneous Echo Contrast. AB - BACKGROUND AND PURPOSE: Spontaneous echo contrast (SEC) is frequently detected in patients with atrial fibrillation (AF). Coexisting SEC in patients with AF may be associated with heightened thrombogenicity, which affects stroke outcomes. METHODS: Consecutive stroke patients with nonvalvular AF who underwent transesophageal echocardiography were included in this study. We compared initial stroke severity and functional outcome at 3 months between the patients with and those without SEC. RESULTS: Of 440 patients with nonvalvular AF who underwent transesophageal echocardiography during a 7-year period, 193 (43.9%) patients had SEC. Stroke was more severe in the patients with SEC than in those without SEC (National Institute of Health Stroke Scale score: median [interquartile range], 5 [2-12] versus 3 [1-8]; P=0.004). The patients with SEC more frequently had poor functional outcomes (modified Rankin scale score of >2) at 3 months than those without SEC (32.3% versus 16.1%; P<0.001). On multivariate analysis, the presence of SEC was an independent factor of poor outcome (odds ratio, 2.09; 95% confidence interval, 1.24-3.53). CONCLUSIONS: In the ischemic stroke patients with nonvalvular AF, coexisting SEC was associated with more severe stroke and was predictive of poor long-term functional outcome. PMID- 27188408 TI - Regulation of energy metabolism and maintenance of metabolic homeostasis: the adiponectin story after 20 years. PMID- 27188407 TI - Incidence of undetected cement on CAD/CAM monolithic zirconia crowns and customized CAD/CAM implant abutments. A prospective case series. AB - OBJECTIVE: The aim of this study was to assess the frequency of cement residues after cementation of CAD/CAM monolithic zirconia crowns on customized CAD/CAM titanium abutments. MATERIALS AND METHODS: Sixty premolars and molars were restored on Astra Tech Osseospeed TXTM implants using single monolithic zirconia crowns fixed on two types of custom-made abutments: AtlantisTM titanium or AtlantisTM Gold Hue. Occlusal openings providing access to the abutment screws were designed for retrievability of the crown/abutment connection. After fixation with glass ionomer cement, the crown/abutment units were unscrewed to evaluate the presence of residual cement. Dichotomous assessment of the presence or absence of cement at the crown/abutment unit and peri-implant tissues was performed. RESULTS: Clinically undetected cement excess was visible on 44 of 60 restorations (73.3%). There was no interdependency between residual cement presence and implant location or diameter. However, a dependency between the presence of residual cement and the aspect of the abutment/crown connection could be noted. The majority of the residues were observed on the distal (17.9%) and mesial (15%) aspects. While on the palatal/lingual aspect, the cement was visible in 8.8%; only 3.4% of all surfaces displayed cement residues. CONCLUSIONS: Within the limitations of the study, it can be concluded that the use of customized CAD/CAM abutments do not guarantee avoidance of subgingival cement residues after crown cementation. PMID- 27188410 TI - A review of occupational therapy's contribution to and involvement in the work-to retirement transition process: An Australian perspective. AB - BACKGROUND: Retirement from paid work is an occupational transition, which can have a profound impact on a person's life. This review explored occupational therapy's contribution to and involvement in the work-to-retirement transition process in Australia. METHODS: An integrative literature review was undertaken using seven article repository databases. PRISMA guidelines informed searches. Articles were included if participants were Australian; researchers' discussed retirement from an occupational perspective or the scope of practice of occupational therapists; and publication was from 1994 to June 2015 in a peer reviewed journal. Articles were critically appraised and thematic analysis explored: (i) occupational perspective, (ii) occupational therapy scope of practice, (iii) theory and (iv) retirement definitions. RESULTS: Eight articles met the review criteria. Three occupational perspective themes were identified: retirement intention influences, retirement preparation and retirement roles and activities. No articles on the current scope of practice of occupational therapy were found. Three articles discussed potential occupational therapy approaches. Three themes on what retirement is were identified: complete cessation, gradual transition and intermittent worker. Four theory themes were identified: occupational therapy, ageing, identity and work. CONCLUSION: Occupational therapy has the potential to be involved in improving health and well-being for people in the work-to-retirement transition process. It is suggested that future research explore not only people's experiences but also the approaches of occupational therapy in assisting people through this occupational transition. The use of theory to guide Australian occupational therapy practice on retirement should also be explored. The use of consistent retirement definitions will assist in understanding research. PMID- 27188411 TI - Utilization of carbon substrates by heterotrophic bacteria through vertical sediment profiles in coastal and estuarine seagrass meadows. AB - Coastal vegetated ecosystems play an important role in carbon cycling and bacterial communities inhabiting coastal sediments are responsible for the remineralization and processing of organic carbon (OC). We collected 1 m-long sediment cores in Posidonia seagrass meadows from coastal and estuarine sites in Australia that differed in their sedimentary organic and inorganic carbon, nitrogen and mud contents. The metabolic diversity of sediment heterotrophic bacterial communities was characterized at different sediment depths, based on the utilization pattern of 31 individual carbon substrates using Biolog EcoPlatesTM . High metabolic diversity was recorded at both sites, but the carbon substrate utilization rates and the use of carbohydrates were higher at the coastal site compared to the estuarine site. The heterotrophic bacterial community in the coastal sediment appeared to metabolize a more diverse OC pool compared to the estuarine site, which might partly explain the differences in OC storage among the seagrass habitats studied. The Biolog EcoPlatesTM provided a useful tool for characterising the sediment heterotrophic bacterial communities in the meadows and sediment characteristics and biochemical composition of the organic matter played an important role in shaping heterotrophic bacterial communities and their carbon utilization rates, potentially affecting carbon accumulation and preservation within seagrass sediments. PMID- 27188409 TI - Microvascular reactivity is altered early in patients with acute respiratory distress syndrome. AB - BACKGROUND: Acute respiratory distress syndrome (ARDS) is associated with vascular endothelial dysfunction. The resultant microvascular reactivity can be assessed non-invasively using near-infrared spectroscopy (NIRS) and a vascular occlusion test (VOT) and changes have been correlated with severity of organ dysfunction and mortality in other critically ill populations. We used NIRS to study the presence of microcirculatory alterations in patients with ARDS. METHODS: We studied 27 healthy volunteers and 32 ARDS patients admitted to our intensive care department. NIRS measurements were performed within 24 h after diagnosis (Berlin definition). VOTs were performed by inflating an arm-cuff to a pressure greater than the systolic pressure for 3 min, followed by rapid deflation. The descending (Desc) and ascending (Asc) thenar muscle oxygen saturation (StO2) slopes were calculated. We compared data from volunteers with those from ARDS patients, from ARDS survivors and non-survivors, and from ARDS survivors who required <7 days ventilatory support (good evolution) with those who required >7 days support or died (poor evolution). RESULTS: ARDS patients had lower StO2 values [75(67-80) vs 79(76-81) %, p = 0.04] and Asc slopes [185(115 233) vs 258(216-306) %/min, p < 0.01] than healthy volunteers, but Desc slopes were similar. The Asc slope was lower in the patients with a poor evolution than in the other patients [121(90-209) vs 222(170-293) %/min, p < 0.01], and in the non-survivors than in the survivors [95(73-120) vs 212(165-252) %/min, p < 0.01]. CONCLUSIONS: In ARDS patients, microvascular reactivity is altered early, and the changes are directly related to the severity of the disease. The ascending slope is the best determinant of outcome. PMID- 27188412 TI - Primary central nervous system posttransplant lymphoproliferative disease: An uncommon diagnostic dilemma. PMID- 27188414 TI - Cataract. AB - Cataract is the leading cause of reversible blindness and visual impairment globally. Blindness from cataract is more common in populations with low socioeconomic status and in developing countries than in developed countries. The only treatment for cataract is surgery. Phacoemulsification is the gold standard for cataract surgery in the developed world, whereas manual small incision cataract surgery is used frequently in developing countries. In general, the outcomes of surgery are good and complications, such as endophthalmitis, often can be prevented or have good ouctomes if properly managed. Femtosecond laser assisted cataract surgery, an advanced technology, can automate several steps; initial data show no superiority of this approach over current techniques, but the results of many large clinical trials are pending. The greatest challenge remains the growing 'backlog' of patients with cataract blindness in the developing world because of lack of access to affordable surgery. Efforts aimed at training additional cataract surgeons in these countries do not keep pace with the increasing demand associated with ageing population demographics. In the absence of strategie that can prevent or delay cataract formation, it is important to focus efforts and resources on developing models for efficient delivery of cataract surgical services in underserved regions. For an illustrated summary of this Primer, visit: http://go.nature.com/eQkKll. PMID- 27188413 TI - Recommendations for sexual expression management in long-term care: a qualitative needs assessment. AB - AIMS: To conduct a qualitative needs assessment of Directors of Nursing regarding challenges and recommendations for addressing sexual expression and consent. BACKGROUND: Sexual expression management among long-term care residents is a complex issue for nursing home staff. Little guidance is available for those wanting to follow a person-centred approach. Policies and procedures are needed, and must be usable across long-term care settings. DESIGN: Qualitative design for in-depth exploration. METHODS: Semi-structured interviews were conducted with 20 Directors of Nursing in the spring and summer of 2013, representing a range of regions, facility sizes and resident populations. Interview questions prompted them to identify recommendations that address challenges to improving sexual expression management in long-term care settings. RESULTS: Comparative thematic analysis resulted in several codes, which were grouped into eight overall categories. Recommendation categories that addressed key challenges included: address the issue, make environmental changes, identify staff expertise, provide education and training, assess sexuality initially and recurrently, establish policies/procedures for sexual expression management, develop assessment tools for sexual expression and consent, and clarify legal issues. The recommendation to develop national guidelines was observed across categories. DISCUSSION: Directors of Nursing report several challenges to sexual expression management in their facilities, and perceive their current methods to be ad hoc. A proactive approach to policy and procedure development is needed. PMID- 27188415 TI - Insulin-like growth factor-I gene therapy increases hippocampal neurogenesis, astrocyte branching and improves spatial memory in female aging rats. AB - In rats, learning and memory performance decline during aging, which makes this rodent species a suitable model to evaluate therapeutic strategies of potential value for correcting age-related cognitive deficits. Some of these strategies involve neurotrophic factors like insulin-like growth factor-I (IGF-I), a powerful neuroprotective molecule in the brain. Here, we implemented 18-day long intracerebroventricular (ICV) IGF-I gene therapy in 28 months old Sprague-Dawley female rats, and assessed spatial memory performance in the Barnes maze. We also studied hippocampal morphology using an unbiased stereological approach. Adenovectors expressing the gene for rat IGF-I or the reporter DsRed were used. Cerebrospinal fluid (CSF) samples were taken and IGF-I levels determined by radioimmunoassay. At the end of the study, IGF-I levels in the CSF were significantly higher in the experimental group than in the DsRed controls. After treatment, the IGF-I group showed a significant improvement in spatial memory accuracy as compared with DsRed counterparts. In the dentate gyrus (DG) of the hippocampus, the IGF-I group showed a higher number of immature neurons than the DsRed controls. The treatment increased hippocampal astrocyte branching and reduced their number in the hippocampal stratum radiatum. We conclude that the ependymal route is an effective approach to increase CSF levels of IGF-I and that this strategy improves the accuracy of spatial memory in aging rats. The favorable effect of the treatment on DG neurogenesis and astrocyte branching in the stratum radiatum may contribute to improving memory performance in aging rats. PMID- 27188417 TI - Fitness to practise process must change, says GMC chair. PMID- 27188416 TI - Erratum to: The risk of cancer in patients with rheumatoid arthritis taking tumor necrosis factor antagonists: a nationwide cohort study. PMID- 27188418 TI - Alpha-ketoglutarate enhances milk protein synthesis by porcine mammary epithelial cells. AB - Alpha-ketoglutarate (AKG), a key intermediate in the Krebs cycle, has been reported to promote protein synthesis through activating mechanistic targeting of rapamycin (mTOR) in enterocytes. The study tested the hypothesis that AKG may enhance growth and milk protein synthesis in porcine mammary epithelial cells (PMECs). PMECs were cultured for 96 h in Dulbecco's modified Eagle's-F12 Ham medium (DMEM-F12) containing prolactin (2 ug/ml) and AKG (0 or 1.5 mM). At the end of 96-h culture, the abundance of apoptosis-related proteins (caspase-3, caspase-9), milk-specific proteins (alpha-lactalbumin and beta-casein), mTOR signaling proteins (mTOR, p-mTOR, PERK, p-PERK, eIF2a, P70S6K and p-P70S6K), and endoplasmic reticulum stress (ERS)-associated proteins (BiP and CHOP) in PMEC were determined. Addition of AKG dose-dependently enhanced cell viability in the absence or presence of prolactin, with optimal concentrations of AKG being at 1.0 and 1.5 mM, respectively. In the presence of prolactin, addition of 1.5 mM AKG: (1) decreased (P < 0.05) the abundance of caspase-3 and caspase-9 by 21 and 39 %; (2) enhanced (P < 0.05) the phosphorylation of p-mTOR and p-P70S6K by 39 and 89 %, respectively; (3) increased (P < 0.05) the production of beta-casein and alpha lactalbumin by 16 and 20 %, respectively; (4) attenuated (P < 0.05) the expression of CHOP by 34 % but promoted (P < 0.05) the expression of BiP by 46 %; (5) increased (P < 0.05) the secretion of lactose by 15 %, when compared to the 0 mM AKG group. Rapamycin (50 nM; an inhibitor of mTOR) attenuated (P < 0.05) the stimulatory effect of AKG on mTOR signaling and syntheses of milk protein and lactose, while relieving (P < 0.05) an inhibitory effect of AKG on expression of proteins related to ERS. Collectively, our results indicate that AKG enhances milk protein production by modulating mTOR and ERS signaling pathways in PMECs. PMID- 27188419 TI - Combination of transglutaminase and sourdough on gluten-free flours to improve dough structure. AB - The aim of this work was to evaluate the effects of microbial transglutaminase (mTG) and sourdough on gluten-free (GF) flours. Besides deamidation and incorporation of amines, mTG catalyses protein cross-links, modifying dough structure. Sourdough from lactic acid bacteria (LAB) and yeast modifies dough protein composition, determining proteolysis, which induce the formation of aroma precursor metabolites. The chemical-physical interactions of volatile molecules with various constituents of the matrix affect the retention of aroma compounds. Here, the effect on volatile molecule profiles and on protein networks formation after mTG treatment in sourdoughs obtained with four GF flours belonging to cereals, pseudo-cereals and legumes (rice, corn, amaranth and lentil) was investigated. Sourdough was prepared with a two-step fermentation using Lactobacillus sanfrancisciensis (LSCE1) and Candida milleri (PFL44), then mTG was added after 21 h of fermentation at increasing levels. The results showed that mTG had the capacity to modify GF flour proteins and improve protein networks formation, involving mainly the prolamin protein fraction. This is particularly relevant for the production of GF backed goods generally lacking of technological, structural and sensorial features compared with products obtained with wheat flour sourdough fermentation. Interestingly, mTG treatment of sourdough affected also the volatile composition and indeed possibly the final organoleptic properties of the products. PMID- 27188420 TI - [In Process Citation]. PMID- 27188421 TI - [The human being-a challenging place to work]. PMID- 27188422 TI - [In Process Citation]. PMID- 27188423 TI - Erratum to: Significant treatment effect of adjunct music therapy to standard treatment on the positive, negative, and mood symptoms of schizophrenic patients: a meta-analysis. PMID- 27188424 TI - Genome scan linkage analysis identifies quantitative trait loci affecting serum clinical-chemical traits in Korean native chicken. AB - Alterations in robustness- and health-related traits lead to physiological changes, such as changes in the serum clinical chemical parameters in individuals. Therefore, clinical-chemical traits can be used as biomarkers to examine the health status of chickens. The aim of the present study was to detect the quantitative trait loci (QTLs) influencing eight clinical-chemical traits (glucose, total protein, creatinine, high-density lipoprotein cholesterol, total cholesterol, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and alpha-amylase) in an F1 nuclear families comprising 83 F0 founders and 585 F1 progeny of Korean native chickens. Genotypic data on 135 DNA markers representing 26 autosomes have been generated for this resource pedigree. The total length of the map was 2729.4 cM. We used a multipoint variance component linkage approach to identify QTLs for the traits. A significant QTL affecting serum alpha-amylase levels was identified on chicken chromosome (GGA) 7 [logarithm of odds (LOD) = 3.02, P value = 1.92 * 10(-4)]. Additionally, we detected several suggestive linkage signals for the levels of total cholesterol, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and creatinine on GGA 4, 12, 13, and 15. In this study, serum alpha-amylase levels related significant QTL was mapped on GGA7 and cholesterol, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and creatinine traits related suggestive QTLs were detected on GGA4, 12, 13 and 15, respectively. Further verification and fine mapping of these identified QTLs can provide valuable information for understanding the variations of clinical chemical trait in chickens. PMID- 27188425 TI - The synergistic risk effect of apolipoprotein epsilon4 and DNA (cytosine-5-) methyltransferase 3 beta (DNMT3B) haplotype for Alzheimer's disease. AB - Alzheimer's disease (AD) is a complex and multifactorial disease with the contribution of several genes and polymorphisms to its development. Among these genes, the APOEepsilon4 is the best known risk factor for AD. Methylation is associated with APOE expression and AD development. Recently, we found an association of the TGG haplotype in the DNMT3B gene, one of the catalyst enzyme for methylation, with AD. Therefore, the objective of the study was to investigate whether APOEepsilon4 and TGG haplotype have an synergistic effect on AD. The sample was composed of 212 Caucasian individuals (108 healthy controls and 104 with AD by NINCDS-ADRDA and DSM-IV-TR criteria) from southern Brazil. The genetic analyses were performed by real time PCR for TaqMan((r)) assay. Multivariate logistic regression was performed categorizing groups according to presence of APOEepsilon4 and/or TGG haplotype as an independent variable for outcome AD. The presence of TGG haplotype plus the allele APOEepsilon4 were strongly associated with AD [OR 11.13; 95 % CI (4.25-29.16); P < 0.001]. This association had a higher risk than each risk factor alone. We found a strong association of the interaction of DNMT3B gene with the APOEepsilon4 in this sample of AD patients. The presence of TGG haplotype and APOEepsilon4 significantly increased the risk of developing the disease, showing an synergistic effect. PMID- 27188426 TI - The genome-wide DNA sequence specificity of the anti-tumour drug bleomycin in human cells. AB - The cancer chemotherapeutic agent, bleomycin, cleaves DNA at specific sites. For the first time, the genome-wide DNA sequence specificity of bleomycin breakage was determined in human cells. Utilising Illumina next-generation DNA sequencing techniques, over 200 million bleomycin cleavage sites were examined to elucidate the bleomycin genome-wide DNA selectivity. The genome-wide bleomycin cleavage data were analysed by four different methods to determine the cellular DNA sequence specificity of bleomycin strand breakage. For the most highly cleaved DNA sequences, the preferred site of bleomycin breakage was at 5'-GT* dinucleotide sequences (where the asterisk indicates the bleomycin cleavage site), with lesser cleavage at 5'-GC* dinucleotides. This investigation also determined longer bleomycin cleavage sequences, with preferred cleavage at 5' GT*A and 5'- TGT* trinucleotide sequences, and 5'-TGT*A tetranucleotides. For cellular DNA, the hexanucleotide DNA sequence 5'-RTGT*AY (where R is a purine and Y is a pyrimidine) was the most highly cleaved DNA sequence. It was striking that alternating purine-pyrimidine sequences were highly cleaved by bleomycin. The highest intensity cleavage sites in cellular and purified DNA were very similar although there were some minor differences. Statistical nucleotide frequency analysis indicated a G nucleotide was present at the -3 position (relative to the cleavage site) in cellular DNA but was absent in purified DNA. PMID- 27188427 TI - Identifying a biomarker network for corticosteroid resistance in asthma from bronchoalveolar lavage samples. AB - Corticosteroid resistance (CR) is a major barrier to the effective treatment of severe asthma. Hence, a better understanding of the molecular mechanisms involved in this condition is a priority. Network analysis is an emerging strategy to explore this complex heterogeneous disorder at system level to identify a small own network for CR in asthma. Gene expression profile of GSE7368 from bronchoalveolar lavage (BAL) of CR in subjects with asthma was downloaded from the gene expression omnibus (GEO) database and compared to BAL of corticosteroid sensitive (CS) patients. DEGs were identified by the Limma package in R language. In addition, DEGs were mapped to STRING to acquire protein-protein interaction (PPI) pairs. Topological properties of PPI network were calculated by Centiscape, ClusterOne and BINGO. Subsequently, text-mining tools were applied to design one own cell signalling for CR in asthma. Thirty-five PPI networks were obtained; including a major network consisted of 370 nodes, connected by 777 edges. After topological analysis, a minor PPI network composed by 48 nodes was indentified, which is composed by most relevant nodes of major PPI network. In this subnetwork, several receptors (EGFR, EGR1, ESR2, PGR), transcription factors (MYC, JAK), cytokines (IL8, IL6, IL1B), one chemokine (CXCL1), one kinase (SRC) and one cyclooxygenase (PTGS2) were described to be associated with inflammatory environment and steroid resistance in asthma. We suggest a biomarker network composed by 48 nodes that could be potentially explored with diagnostic or therapeutic use. PMID- 27188428 TI - Chidamide alleviates TGF-beta-induced epithelial-mesenchymal transition in lung cancer cell lines. AB - Transforming growth factor-beta (TGF-beta)-induced epithelial-mesenchymal transition is a critical process in the initiation of metastasis of various types of cancer. Chidamide is a class I histone deacetylase inhibitor with anti-tumor activity. This study investigated the effects of chidamide on TGF-beta-mediated suppression of E-cadherin expression in adenocarcinomic lung epithelial cells and the molecular mechanisms involved in these effects. Western blot analysis, confocal microscopy, Quantitative methyl-specific PCR and bisulfite sequencing were used to evaluate the effects of different treatments on chidamide ameliorating TGF-beta induced-E-cadherin loss. H3 acetylation binding to the promoter of E-cadherin was detected by chromatin immunoprecipitations (CHIP). We found that chidamide reduced the level of lung cancer cell migration observed using a Boyden chamber assay (as an indicator of metastatic potential). Chidamide inhibited TGF-beta-induced SMAD2 phosphorylation and attenuated TGF-beta-induced loss of E-cadherin expression in lung cancer cells by Western blotting and confocal microscopy, respectively. Quantitative methyl-specific PCR and bisulfite sequencing revealed that TGF-beta-enhanced E-cadherin promoter methylation was ameliorated in cells treated with chidamide. We demonstrated that histone H3 deacetylation within the E-cadherin promoter was required for TGF-beta-induced E cadherin loss; cell treatment with chidamide increased the H3 acetylation detected by CHIP. Taken together, our results demonstrate that TGF-beta suppressed E-cadherin expression by regulating promoter methylation and histone H3 acetylation. Chidamide significantly enhanced E-cadherin expression in TGF beta-treated cells and inhibited lung cancer cell migration. These findings indicate that chidamide has a potential therapeutic use due to its capacity to prevent cancer cell metastasis. PMID- 27188429 TI - In vitro assessment of the tooth staining potential of endodontic materials in a bovine tooth model. AB - BACKGROUND/AIMS: Traumatized teeth requiring endodontic intervention may discolor as a result of the treatment performed. Thus, the aim was to investigate the discoloration potential of different endodontic cements, dressings, and irrigants used in dental traumatology. MATERIALS AND METHODS: Cylindrical cavities were prepared in 330 bovine enamel-dentine blocks (10 * 10 * 3.5 mm), leaving 2 mm of enamel and dentine on the labial side. The specimens were randomly assigned to 22 groups (n = 15). The cavities were filled with a range of endodontic materials, sealed with composite and stored in physiological saline. The color of the labial enamel surface was measured with a spectrophotometer at 7 time intervals: before (T0) and after the placement of the test material (T1 = baseline), after 1 week (T2), 1 month (T3), 3 months (T4), 6 months (T5), and 12 months (T6). The color difference values (DeltaE) were calculated and further analyzed by anova and the Tukey-Kramer post hoc test (alpha = 0.05). RESULTS: After 12 months, significant staining was observed among the endodontic cements only in the Portland cement group with additional bismuth oxide (H-MED PC BiOx; DeltaE 22.2). Specimens with other commercially available calcium silicate cements containing bismuth oxide were not significantly discolored. All specimens with endodontic dressings and irrigants were color stable except the tested triple antibiotic paste (M TreVitaMix; DeltaE 14.9) and the double antibiotic paste (N-BiMix; DeltaE 14.9). Both mixtures did not contain tetracycline derivatives. CONCLUSIONS: The presence of bismuth oxide in calcium silicate cements was not shown to be a reliable predictor for tooth discoloration. Antibiotic pastes without tetracycline derivatives do not guarantee the color stability of teeth. PMID- 27188430 TI - The Prevalence of Common Mental Disorders Among South Africans Seeking HIV Testing. AB - We administered the Structured Clinical Interview for the DSM to 485 persons seeking HIV testing at five community testing centres in South Africa to determine the prevalence of common mental disorders among this population. The prevalence estimates for the various disorders were as follows: major depressive disorder: 14.2 % (95 % CI [11.1, 17.3]); generalised anxiety disorder 5.0 % (95 % CI [3.07, 6.93]); posttraumatic stress disorder 4.9 % (95 % CI [2.98, 6.82]); and alcohol use disorder 19.8 % (95 % CI [16.26, 23.34]). Our findings imply the need to research the integration of screening and referral trajectories in the context of voluntary HIV counselling and testing. PMID- 27188432 TI - France's Evin Law on the control of alcohol advertising: content, effectiveness and limitations. AB - AIMS: To assess the effectiveness of the 2015 version of the French Evin Law that was implemented in 1991 with the objective of protecting young people from alcohol advertising. DESIGN: Data were obtained from survey questions measuring exposure and receptivity to alcohol advertisements that were introduced for the first time in the 2015 European School Survey Project on Alcohol and Other Drugs (ESPAD). PARTICIPANTS AND SETTING: A representative sample of 6642 10th-12th grade students (mean age 17.3 years) were interviewed in 198 schools in France by a self-administered questionnaire. MEASUREMENTS: Information was collected on alcohol advertising exposure in different media (outside billboards, internet, etc.) and receptivity to recent advertisements (attractiveness, incentive to drink, etc.). FINDINGS: The majority of students declared that they had been exposed at least once a month to alcohol advertisements in supermarkets (73.2%), in movies (66.1%), magazines and newspapers (59.1%), on billboards in streets (54.5%), and on the internet (54.1%). Concerning the last recalled advertisements, 27.8% remembered the beverage type, 18.2% the brand, 13% felt like having a drink after having seen the advertisement and 19.6% found the advertisement attractive (boys ranked significantly higher than girls for all these indicators; P-value < 0.05). CONCLUSION: The 2015 version of the French Evin law does not appear to protect young people effectively from exposure to alcohol advertising in France. PMID- 27188431 TI - Effects of heated hydrotherapy on muscle HSP70 and glucose metabolism in old and young vervet monkeys. AB - Increasing heat shock protein 70 (HSP70) in aged and/or insulin-resistant animal models confers benefits to healthspan and lifespan. Heat application to increase core temperature induces HSPs in metabolically important tissues, and preliminary human and animal data suggest that heated hydrotherapy is an effective method to achieve increased HSPs. However, safety concerns exist, particularly in geriatric medicine where organ and cardiovascular disease commonly will preexist. We evaluated young vervet monkeys compared to old, insulin-resistant vervet monkeys (Chlorocebus aethiops sabaeus) in their core temperatures, glucose tolerance, muscle HSP70 level, and selected safety biomarkers after 10 sessions of hot water immersions administered twice weekly. Hot water immersion robustly induced the heat shock response in muscles. We observed that heat-treated old and young monkeys have significantly higher muscle HSP70 than control monkeys and treatment was without significant adverse effects on organ or cardiovascular health. Heat therapy improved pancreatic responses to glucose challenge and tended to normalize glucose excursions. A trend for worsened blood pressure and glucose values in the control monkeys and improved values in heat-treated monkeys were seen to support further investigation into the safety and efficacy of this intervention for metabolic syndrome or diabetes in young or old persons unable to exercise. PMID- 27188433 TI - MicroRNA-21 promotes cell proliferation, migration, and resistance to apoptosis through PTEN/PI3K/AKT signaling pathway in esophageal cancer. AB - Our study aimed to explore associations between microRNA-21 (miR-21) and PTEN/PI3K/AKT signaling pathway and, further, to elucidate the regulation of miR 21 on biological behaviors in human esophageal cancer cells. The expressions of miR-21, PTEN, PI3K, and AKT were detected in 89 esophageal cancer samples and 58 adjacent normal tissues respectively. The human esophageal cancer cells (TE11) were grouped as following: blank (TE11 cells without transfection), negative (TE11 cells with miR-21 negative inhibitor), and Inhibition-miR21 (TE11 cells with miR-21 inhibitor). Western blot was used for detection of PTEN, P13K, and AKT protein expressions, MTT method for cell proliferation, Transwell assay for cell migration and invasion, and flow cytometry for cell cycle and apoptosis. MiR 21, PI3K, and AKT have higher expressions, but PTEN has lower expression in esophageal cancer tissues compared with adjacent normal tissues. The esophageal cancer tissues with lymph node metastasis and poor differentiation showed significantly low positive rate of PTEN protein, but high positive rates of PI3K and AKT proteins. Compared with blank and negative groups, PTEN expression of TE11 cells in Inhibition-miR21 group was significantly up-regulated, but PI3K and AKT were down-regulated. Further, PTEN was a target gene of miR-21. Besides, compared with blank and negative groups, the proliferation, migration, and invasion of TE11 cells were less active in Inhibition-miR21 group. TE11 cells were significantly increased in the G0/G1 phase of cell cycles, but decreased in the S and G2/M phase in Inhibition-miR21 group. The TE11 cells exhibited significantly increased apoptosis rates. MiR-21 targets key proteins in PTEN/PI3K/AKT signal pathway, promoting proliferation, migration, invasion, and cell cycle, and inhibiting apoptosis of human esophageal cancer cells. It may serve as a novel therapeutic target in esophageal cancer. PMID- 27188434 TI - EMMLi: A maximum likelihood approach to the analysis of modularity. AB - Identification of phenotypic modules, semiautonomous sets of highly correlated traits, can be accomplished through exploratory (e.g., cluster analysis) or confirmatory approaches (e.g., RV coefficient analysis). Although statistically more robust, confirmatory approaches are generally unable to compare across different model structures. For example, RV coefficient analysis finds support for both two- and six-module models for the therian mammalian skull. Here, we present a maximum likelihood approach that takes into account model parameterization. We compare model log-likelihoods of trait correlation matrices using the finite-sample corrected Akaike Information Criterion, allowing for comparison of hypotheses across different model structures. Simulations varying model complexity and within- and between-module contrast demonstrate that this method correctly identifies model structure and parameters across a wide range of conditions. We further analyzed a dataset of 3-D data, consisting of 61 landmarks from 181 macaque (Macaca fuscata) skulls, distributed among five age categories, testing 31 models, including no modularity among the landmarks and various partitions of two, three, six, and eight modules. Our results clearly support a complex six-module model, with separate within- and intermodule correlations. Furthermore, this model was selected for all five age categories, demonstrating that this complex pattern of integration in the macaque skull appears early and is highly conserved throughout postnatal ontogeny. Subsampling analyses demonstrate that this method is robust to relatively low sample sizes, as is commonly encountered in rare or extinct taxa. This new approach allows for the direct comparison of models with different parameterizations, providing an important tool for the analysis of modularity across diverse systems. PMID- 27188435 TI - Highly Efficient and Scalable Separation of Semiconducting Carbon Nanotubes via Weak Field Centrifugation. AB - The identification of scalable processes that transfer random mixtures of single walled carbon nanotubes (SWCNTs) into fractions featuring a high content of semiconducting species is crucial for future application of SWCNTs in high performance electronics. Herein we demonstrate a highly efficient and simple separation method that relies on selective interactions between tailor-made amphiphilic polymers and semiconducting SWCNTs in the presence of low viscosity separation media. High purity individualized semiconducting SWCNTs or even self organized semiconducting sheets are separated from an as-produced SWCNT dispersion via a single weak field centrifugation run. Absorption and Raman spectroscopy are applied to verify the high purity of the obtained SWCNTs. Furthermore SWCNT - network field-effect transistors were fabricated, which exhibit high ON/OFF ratios (10(5)) and field-effect mobilities (17 cm(2)/Vs). In addition to demonstrating the feasibility of high purity separation by a novel low complexity process, our method can be readily transferred to large scale production. PMID- 27188436 TI - Lingunite-a high-pressure plagioclase polymorph at mineral interfaces in doleritic rock of the Lockne impact structure (Sweden). AB - Lingunite nanocrystals and amorphous plagioclase (maskelynite) are identified at the contacts between augite and labradorite wedge-shaped interfaces in the doleritic rocks of the Lockne impact structure in Sweden. The occurrence of lingunite suggests that the local pressure was above 19 GPa and the local temperature overwhelmed 1000 degrees C. These values are up to 10 times higher than previous values estimated numerically for bulk pressure and temperature. High shock-induced temperatures are manifested by maskelynite injections into microfractures in augite located next to the wedges. We discuss a possible model of shock heterogeneity at mineral interfaces, which may lead to longer duration of the same shock pressure and a concentration of high temperature thus triggering the kinetics of labradorite transformation into lingunite and maskelynite. PMID- 27188437 TI - Synthesis and Biological Evaluation of New N-(4-Substituted phenyl)glycine Derivatives as Potential Anti-inflammatory Agents. AB - BACKGROUND: Designing new anti-inflammatory agents possessing safe therapeutic profiles and devoid of potential undesirable side effects is an active field in medicinal chemistry. Thus, a series of N-(4-substituted phenyl)glycine derivatives was designed and synthesized. The idea behind the design is to utilize the bifunctionality of 4-aminoacetophenone via converting the amino group into glycine derivative as a side arm to mimic the glycine amino acid enhancing the overall physicochemical and biological characteristics. In addition, the opposite acetyl group was used as a center for modification and derivatization. METHODS: The starting N-(4-acetylphenyl)glycine was converted into two intermediates: the chalcone analog 2 and the thiosemicarbazone derivative 8. Both 2 and 8 were derivatized and/or cyclized into different heterocyclic target derivatives (3-7 and 9-12). The target compounds were screened for anti inflammatory activity using carrageenan-induced rat paw edema assay. RESULTS: The results showed that compounds 6, 7, and 3, were the most active among the tested compounds at 50 mg/kg dose level with % inhibition of edema of 51.82, 43.80, and 40.39, respectively. CONCLUSION: The authors succeeded to introduce a simple and versatile skeleton with a side arm resembling the glycine amino acid; imparting a potential improvement in physicochemical properties. We utilize the other side of the skeleton's aromatic ring as a center for derivatization. The chalcone analog and its cyclized heterocyclic derivatives were of remarkably higher anti inflammatory activity than the thiosemicarbazone and its derivatives. PMID- 27188438 TI - Uncertainty in clinical practice - an interview study with Swedish GPs on patients with sore throat. AB - BACKGROUND: Uncertainty is inevitable in clinical practice in primary care and tolerance for uncertainty and concern for bad outcomes has been shown to vary between physicians. Uncertainty is a factor for inappropriate antibiotic prescribing. Evidence-based guidelines as well as near-patient tests are suggested tools to decrease uncertainty in the management of patients with respiratory tract infections. The aim of this paper was to describe strategies for coping with uncertainty in patients with pharyngotonsillitis in relation to guidelines. METHODS: An interview study was conducted among a strategic sample of 25 general practitioners (GPs). RESULTS: All GPs mentioned potential dangerous differential diagnoses and complications. Four strategies for coping with uncertainty were identified, one of which was compliant with guidelines, "Adherence to guidelines", and three were idiosyncratic: "Clinical picture and C reactive protein (CRP)", "Expanded control", and "Unstructured". The residual uncertainty differed for the different strategies: in the strategy "Adherence to guidelines" and "Clinical picture and CRP" uncertainty was avoided, based either on adherence to guidelines or on the clinical picture and near-patient CRP; in the strategy "Expanded control" uncertainty was balanced based on expanded control; and in the strategy "Unstructured" uncertainty prevailed in spite of redundant examination and anamnesis. CONCLUSION: The majority of the GPs avoided uncertainty and deemed they had no problems. Their strategies either adhered to guidelines or comprised excessive use of tests. Thus use of guidelines as well as use of more near-patient tests seemed associated to reduced uncertainty, although the later strategy at the expense of compliance to guidelines. A few GPs did not manage to cope with uncertainty or had to put in excessive work to control uncertainty. PMID- 27188439 TI - Post-renal transplant infections: single-center experience from Nigeria. AB - BACKGROUND: Infections are the leading cause of hospitalization and mortality in transplant recipients. Nigeria has a growing number of renal transplant recipients. The aim of this study was to determine the pattern of infections in renal allograft recipients in one of the major renal transplant centers in Nigeria. METHODS: All case records of renal allograft recipients on follow-up were retrieved. Those that had infection at any time after transplantation were selected. Demographic and clinical information was collected and analyzed. RESULTS: Thirty-three case records were analyzed, out of which 24/33 (72.7%) were males, with a mean age of 42.3 years (+/- 7.38). The median duration of developing infection post transplant was 270 days (range 2-2190). Most of the infections occurred after 6 months in 15/33 (45.5%). Urinary tract infection was the most common infection, noted in 13/33 (39.4%), followed by pneumonia, which was seen in 12 (33.3%), 9/12 (75%) of which were culture-positive. There were 2 cases (5.6%) of tuberculosis and 1 case (2.8%) of cytomegalovirus colitis. Out of the 9 culture-positive pneumonia cases, 6 (66.7%) were caused by gram-negative pathogens, with Pseudomonas aeruginosa being the most common isolate seen in 3/9 (33.3%) of the patients. Among those with urinary tract infection, Escherichia coli and Klebsiella species were isolated with equal proportion in 3/13 (23.1%), while Enterococcus faecalis was the most common isolate in 4/13 (30.8%). Overall infection-related mortality was 10/33 (30.3%), out of which 5/10 (50%) of deaths were from pneumonia. CONCLUSION: Post-transplant infection surveillance must be strengthened. The role of multidrug-resistant gram-negative bacteria in post renal transplant infection in Nigeria needs to be evaluated. PMID- 27188440 TI - Mice lacking the intracellular cation channel TRIC-B have compromised collagen production and impaired bone mineralization. AB - The trimeric intracellular cation (TRIC) channels TRIC-A and TRIC-B localize predominantly to the endoplasmic reticulum (ER) and likely support Ca(2+) release from intracellular stores by mediating cationic flux to maintain electrical neutrality. Deletion and point mutations in TRIC-B occur in families with autosomal recessive osteogenesis imperfecta. Tric-b knockout mice develop neonatal respiratory failure and exhibit poor bone ossification. We investigated the cellular defect causing the bone phenotype. Bone histology indicated collagen matrix deposition was reduced in Tric-b knockout mice. Osteoblasts, the bone depositing cells, from Tric-b knockout mice exhibited reduced Ca(2+) release from ER and increased ER Ca(2+) content, which was associated with ER swelling. These cells also had impaired collagen release without a decrease in collagen-encoding transcripts, consistent with a defect in trafficking of collagen through ER. In contrast, osteoclasts, the bone-degrading cells, from Tric-b knockout mice were similar to those from wild-type mice. Thus, TRIC-B function is essential to support the production and release of large amounts of collagen by osteoblasts, which is necessary for bone mineralization. PMID- 27188441 TI - BTG1 ameliorates liver steatosis by decreasing stearoyl-CoA desaturase 1 (SCD1) abundance and altering hepatic lipid metabolism. AB - Liver steatosis, a condition in which lipid accumulates in liver cells, is a leading cause of many liver diseases. The livers of patients with hepatocellular carcinoma, a cancer characterized by liver steatosis, have decreased abundance of the transcription cofactor BTG1 (B cell translocation gene 1). We showed that the livers of db/db mice, which are a genetic model of obesity, had decreased BTG1 mRNA and protein abundance. BTG1 overexpression ameliorated liver steatosis in db/db mice, whereas knockdown of BTG1 induced liver steatosis in wild-type mice. Consistent with these changes, we found that BTG1 decreased triglyceride accumulation in cultured hepatocytes. BTG1 overexpression inhibited the expression of the gene encoding stearoyl-CoA desaturase 1 (SCD1), an enzyme involved in the synthesis of fatty acids, by suppressing the activity of activating transcription factor 4 (ATF4). Knockdown of SCD1 prevented liver steatosis in wild-type mice induced by knockdown of BTG1. Conversely, the ability of BTG1 overexpression to ameliorate liver steatosis in db/db mice was negated by ATF4 overexpression. Moreover, BTG1 transgenic mice were resistant to liver steatosis induced by a high-carbohydrate diet. BTG1 abundance was decreased by this diet through a pathway that involved mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase 1 (S6K1), and cAMP response element-binding protein (CREB). Together, our study identifies a role of BTG1 in regulating hepatic lipid metabolism and specifically in preventing ATF4 and SCD1 from inducing liver steatosis. PMID- 27188442 TI - Themis1 enhances T cell receptor signaling during thymocyte development by promoting Vav1 activity and Grb2 stability. AB - The T cell signaling protein Themis1 is essential for the positive and negative selection of thymocytes in the thymus. Although the developmental defect that results from the loss of Themis1 suggests that it enhances T cell receptor (TCR) signaling, Themis1 also recruits Src homology 2 domain-containing phosphatase-1 (SHP-1) to the vicinity of TCR signaling complexes, suggesting that it has an inhibitory role in TCR signaling. We used TCR signaling reporter mice and quantitative proteomics to explore the role of Themis1 in developing T cells. We found that Themis1 acted mostly as a positive regulator of TCR signaling in vivo when receptors were activated by positively selecting ligands. Proteomic analysis of the Themis1 interactome identified SHP-1, the TCR-associated adaptor protein Grb2, and the guanine nucleotide exchange factor Vav1 as the principal interacting partners of Themis1 in isolated mouse thymocytes. Analysis of TCR signaling in Themis1-deficient and Themis1-overexpressing mouse thymocytes demonstrated that Themis1 promoted Vav1 activity both in vitro and in vivo. The reduced activity of Vav1 and the impaired T cell development in Themis1(-/-) mice were due in part to increased degradation of Grb2, which suggests that Themis1 is required to maintain the steady-state abundance of Grb2 in thymocytes. Together, these data suggest that Themis1 acts as a positive regulator of TCR signaling in developing T cells, and identify a mechanism by which Themis1 regulates thymic selection. PMID- 27188444 TI - Hybrid two-stage repair of thoracoabdominal aortic aneurysm. AB - Thoracoabdominal aortic aneurysm is a challenging disease that often requires an invasive surgical repair. Recently, a less invasive hybrid approach has been proposed to improve postoperative outcomes in high-risk patients. It consists of an open first stage where arterial visceral rerouting is obtained, using a vascular graft followed by a second stage where the remaining thoracoabdominal aorta is covered with a stent graft. Initial results using this approach seem promising. Here, we sought to describe the hybrid two-stage technique that is most frequently used in this extensive aortic pathology. PMID- 27188443 TI - Following the trail of lipids: Signals initiated by PI3K function at multiple cellular membranes. AB - Phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3] is the signaling currency of the phosphoinositide 3-kinase (PI3K)/AKT pathway; transduction through this axis depends on this signaling lipid. Formation of PtdIns(3,4,5)P3 is dictated not only by PI3K activation but also by the localization and access of PI3K to its substrate PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate). PI3K/AKT-mediated signaling is antagonized by PtdIns(3,4,5)P3 dephosphorylation. Although previously typically considered an event associated with the plasma membrane, it is now appreciated that the formation and metabolism of PtdIns(3,4,5)P3 occur on multiple membranes with distinct kinetics. Modulated activity of phosphatidylinositol lipid kinases and phosphatases contributes to intricately orchestrated lipid gradients that define the signaling status of the pathway at multiple sites within the cell. PMID- 27188445 TI - Transcarotid transcatheter aortic valve implantation. AB - Transcatheter aortic valve implantation is a well-recognized treatment option for high-risk patients with aortic stenosis. The femoral approach is possible in 80% of cases. Initially, only the transcarotid and subclavian approaches were performed as alternative routes. Both approaches have advantages and disadvantages. The carotid approach is a new approach that offers direct vascular access to the aortic valve. The technique of access is very simple and well known to all cardiovascular surgeons, and the morbidity is minimal. It avoids a thoracotomy with all its complications. We present here our technique and results of our initial experience. PMID- 27188446 TI - Surgical technique of double switch procedure: Senning with arterial switch operation for congenitally corrected transposition of the great arteries with ventricular septal defect. AB - We present a case of 12-month-old boy with congenitally corrected transposition of great arteries with L-looped ventricles and L-transposition of great arteries and ventricular septal defect. When admitted to the hospital, the patient had the appearance of congestive heart failure due to moderate to severe tricuspid valve regurgitation and right ventricle dysfunction. The pulmonary artery (PA) banding was required first because of low systolic pressure in the morphological left ventricle less than 70% confirmed by catheterization. Three months later, the patient appeared to be a good candidate for anatomical repair and a double switch procedure-Senning with arterial switch-was performed. The early postoperative period was relatively smooth and uneventful. Tricuspid valve insufficiency was resolved immediately after surgery. Mild systolic dysfunction of the left ventricle with mild mitral insufficiency was confirmed by the 2D strain method of echocardiography on the second day of the postoperative period and it improved over the next 21 days. Thirty days later after the procedure, the patient underwent catheterization of his superior vena cava tunnel because of the slightly increased blood flow velocity diagnosed by echocardiography. In 3 months after the surgery, the boy was asymptomatic and was doing well. The patient's functional status was I according to the NYHA classification. PMID- 27188447 TI - Nested data independent MS/MS acquisition. AB - Data independent acquisition (DIA) attempts to provide comprehensive MS/MS data while providing a cycle time that is capable of following the elution profile of chromatographic peaks. Currently available MS technology is not yet fully capable of fulfilling these expectations. This paper suggests a new multiplex-based approach to more closely achieve this objective. Customized scans have been programmed for a Q Orbitrap instrument. Multiple nonadjacent mass range segments are sequentially collected (cut out) by the quadrupole. These combined mass ranges undergo fragmentation, and the resulting product ions are analyzed as a whole by the Orbitrap analyzer. The systematical variation of the mass range segments (nested design) permits the mathematical assignment of the observed product ions within a narrow precursor mass range. The proposed approach allows the use of mass windows that are narrower than those in conventional DIA (SWATH). A unique aspect of the proposed approach is the fact that halving the mass window width requires the addition of only a single multiplexed scan. This is different from conventional DIA, which requires the number of mass windows to be doubled in order to achieve the same objective. This paper shows that for a given cycle time, the proposed nested DIA technique produces significantly less chimeric product ion spectra than conventional DIA. However, further improvements from the programming, and most likely the hardware side, are still required in order to achieve the aim of comprehensive MS/MS. Graphical Abstract Schematic of nested design. PMID- 27188448 TI - Self-weighing behavior in individuals with eating disorders. AB - OBJECTIVE: To describe the frequency of self-weighing and reactions to prescribed weekly weighing among individuals with eating disorder (ED) diagnoses, and to compare individuals weighing more or less frequently on mass index (BMI) and the Eating Disorder Examination (EDE) subscales. METHOD: Baseline EDE and demographics from five studies (N = 758). RESULTS: Self-weighing was most frequent among individuals with anorexia nervosa (AN), followed by those with bulimia nervosa (BN) and binge eating disorder (BED). On average, participants reacted moderately negative to prescribed weekly weighing. No relationship between weighing frequency and BMI was evident in any sample. There was indication of greater pathology (i.e., restraint, shape concern, weight concern, global) in AN with more frequent weighing. In BN, mixed evidence emerged to support a relationship between more frequent weighing and higher shape concern, weight concern, and global score. In BED, higher restraint was found in those who weighed versus those who did not. DISCUSSION: Weighing frequency in each eating disorder (ED) sample was to some extent associated with greater ED severity, but not BMI. Future research should examine relationships between self-weighing, reactions to changing weighing frequency, and ED symptomatology in both ED and non-ED groups to understand the impact of self-weighing in heterogeneous populations. (c) 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:817 821). PMID- 27188449 TI - Insight into structure dynamics of soil microbiota mediated by the richness of replanted Pseudostellaria heterophylla. AB - Consecutive monoculture of crops causes serious diseases and significant decline in yield and quality, and microbes in the rhizosphere are closely linked with plant health. Here we systematically studied the structure dynamics of soil microbiota in the monocropping system of Pseudostellaria heterophlla. The results illustrated that the successive cropping of P. heterophylla shifts the diversity and structure of microbial community in rhizosphere soil of P. heterophylla, showing that the diversity of microbial community in rhizosphere soil of P. heterophylla was decreased with the increase of planting years while the structure of microbial community became more deteriorative. Moreover, the population size of typical pathogens increased and the beneficial bacterial population decreased with the increasing years of monoculture, which resulted in the microecological imbalance in P. heterophylla rhizosphere, thereby caused serious replanting diseases in monocropping system. Our results suggested that structure dynamics of rhizosphere microbial communities were mediated by the richness of replanted P. heterophylla, and thus the replant disease result from the imbalanced microbial structure with a higher ratio of pathogens/beneficial bacteria in rhizosphere soil under monocropping regimes. This finding provides a clue to open a new avenue for modulating the root microbiome to enhance the crop production and sustainability. PMID- 27188450 TI - Paneth Cell in Adenomas of the Distal Colorectum Is Inversely Associated with Synchronous Advanced Adenoma and Carcinoma. AB - Recent studies have linked appearance of Paneth cells in colorectal adenomas to adenoma burden and male gender. However, the clinical importance of Paneth cells' associations with synchronous advanced adenoma (AA) and colorectal carcinoma (CRC) is currently unclear. We performed a comprehensive case-control study using 1,900 colorectal adenomas including 785 from females, and 1,115 from males. We prospectively reviewed and recorded Paneth cell status in the colorectal adenomas consecutively collected between February 2014 and June 2015. Multivariable logistic regression analyses revealed that, in contrast to the adenomas without Paneth cells, the Paneth cell-containing adenomas at distal colorectum were inversely associated with presence of a synchronous AA or CRC (odds ratio [OR] 0.39, P = 0.046), whereas no statistical significance was reached for Paneth cell containing proximal colorectal adenomas (P = 0.33). Synchronous AA and CRC were significantly associated with older age (60 + versus <60 years, OR 1.60, P = 0.002), male gender (OR 1.42, P = 0.021), and a history of AA or CRC (OR 2.31, P < 0.001). However, synchronous CRC was not associated with Paneth cell status, or a history of AA or CRC. Paneth cell presence in the adenomas of distal colorectum may be a negative indicator for synchronous AA and CRC, and seems to warrant further studies. PMID- 27188451 TI - Rapid and efficient magnetization of mesenchymal stem cells by dendrimer functionalized magnetic nanoparticles. AB - AIM: Rapid and efficient magnetization of human bone marrow stromal cells (BMSC) through functionalized magnetic nanoparticles (MNP). METHODS: MNP were functionalized with poly(epsilon-lysine) dendrons exposing carboxybetaine residue (CB-MNP) to enhance binding to the cellular glycocalix. BMSC were incubated with CB-MNP or non-functionalized PAA-MNP for 5-30 min in suspension. RESULTS: CB-MNP functionalization increased the magnetization efficiency by threefold. Remarkably, 66% of cells were magnetized after only 5 min and the maximum efficiency of >80% was reached by 15 min. BMSC viability, proliferation and differentiation were not impaired: actually, adipogenic and osteogenic differentiation were even improved. CONCLUSION: Carboxybetaine-dendron functionalization ensured rapid and efficient BMSC magnetization and allowed innovative suspension labeling, with a potential for bypassing adhesion culture of progenitors for regenerative medicine. PMID- 27188453 TI - Clinical and genetic characterization of congenital hyperinsulinism in Spain. AB - CONTEXT: Congenital hyperinsulinism (CHI) is a clinically and genetically heterogeneous disease characterized by severe hypoglycemia caused by inappropriate insulin secretion by pancreatic beta-cells. OBJECTIVE: To characterize clinically and genetically CHI patients in Spain. DESIGN AND METHODS: We included 50 patients with CHI from Spain. Clinical information was provided by the referring clinicians. Mutational analysis was carried out for KCNJ11, ABCC8, and GCK genes. The GLUD1, HNF4A, HNF1A, UCP2, and HADH genes were sequenced depending on the clinical phenotype. RESULTS: We identified the genetic etiology in 28 of the 50 CHI patients tested: 21 had a mutation in KATP channel genes (42%), three in GLUD1 (6%), and four in GCK (8%). Most mutations were found in ABCC8 (20/50). Half of these patients (10/20) were homozygous or compound heterozygous, with nine being unresponsive to diazoxide treatment. The other half had heterozygous mutations in ABCC8, six of them being unresponsive to diazoxide treatment and four being responsive to diazoxide treatment. We identified 22 different mutations in the KATP channel genes, of which ten were novel. Notably, patients with ABCC8 mutations were diagnosed earlier, with lower blood glucose levels and required higher doses of diazoxide than those without a genetic diagnosis. CONCLUSIONS: Genetic analysis revealed mutations in 56% of the CHI patients. ABCC8 mutations are the most frequent cause of CHI in Spain. We found ten novel mutations in the KATP channel genes. The genetic diagnosis is more likely to be achieved in patients with onset within the first week of life and in those who fail to respond to diazoxide treatment. PMID- 27188455 TI - Long-Term Effects of Sports Concussions: Bridging the Neurocognitive Repercussions of the Injury with the Newest Neuroimaging Data. AB - Little is known of the long-term effects of sports-related concussion. Within the scientific literature, conclusions vary substantially where some work suggests there are no long-term consequences at all and other studies show rampant neurodegeneration thought to be caused by sometimes even a single concussive blow to the head. There is growing evidence that supports multiple long-term outcomes, showing both subclinical and clinically relevant changes in the brains of athletes, young and old alike. This article reviews the pathohistology of cerebral concussions and examines the extant literature with a focus on electrophysiological and neuroimaging findings. Neurobehavioral and neurocognitive changes are also reviewed, particularly as they are related to chronic traumatic encephalopathy. Lacunae within the literature are explored, and future research directions are proposed. PMID- 27188454 TI - Human chorionic gonadotropin stimulation gives evidence of differences in testicular steroidogenesis in Klinefelter syndrome, as assessed by liquid chromatography-tandem mass spectrometry. AB - BACKGROUND: Men with Klinefelter syndrome (KS) show hypergonadotropic hypogonadism, but the pathogenesis of hypotestosteronemia remains unclear. Testicular steroidogenesis in KS men was evaluated over three decades ago after human chorionic gonadotropin (hCG) stimulation, but inconclusive results were obtained. Intriguingly, some recent studies show increased intratesticular testosterone concentrations in men with KS. OBJECTIVE: To analyze serum steroid profile, as a proxy of testicular steroidogenesis, after hCG stimulation in KS compared with control men. DESIGN: A prospective, longitudinal, case-control, clinical trial. METHODS: Thirteen KS patients (36+/-9 years) not receiving testosterone (TS) replacement therapy and 12 eugonadic controls (32+/-8 years) were enrolled. Serum steroids were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) at baseline and for five consecutive days after intramuscular injection of 5000IU hCG. RESULTS: Progesterone (P), 17 hydroxyprogesterone (17OHP), TS, and estradiol (E2) showed a significant increase (P<0.001) after hCG stimulation in both groups. On the contrary, androstenedione (AS) and dehydroepiandrosterone did not increase after hCG stimulation. The 17OHP/P ratio increased in both groups (P<0.001), the TS/AS ratio (17beta hydroxysteroid dehydrogenase type 3 (17betaHSD3) activity) did not increase after hCG in any group, and the E2/TS ratio (aromatase activity) increased significantly in both groups (P=0.009 in KS and P<0.001 in controls). Luteinizing hormone decreased after hCG in both groups (P=0.014 in KS and P<0.001 in controls), whereas follicle-stimulating hormone decreased only in control men (P<0.001). CONCLUSION: This study demonstrates for the first time using LC-MS/MS that Leydig cells of KS men are able to respond to hCG stimulation and that the first steps of steroidogenesis are fully functional. However, the TS production in KS men is impaired, possibly related to reduced hydroxysteroid deydrogenase activity due to an unfavorable intratesticular metabolic state. PMID- 27188456 TI - Calpains: Master Regulators of Synaptic Plasticity. AB - Although calpain was proposed to participate in synaptic plasticity and learning and memory more than 30 years ago, the mechanisms underlying its activation and the roles of different substrates have remained elusive. Recent findings have provided evidence that the two major calpain isoforms in the brain, calpain-1 and calpain-2, play opposite functions in synaptic plasticity. In particular, while calpain-1 activation is the initial trigger for certain forms of synaptic plasticity, that is, long-term potentiation, calpain-2 activation restricts the extent of plasticity. Moreover, while calpain-1 rapidly cleaves regulatory and cytoskeletal proteins, calpain-2-mediated stimulation of local protein synthesis reestablishes protein homeostasis. These findings have important implications for our understanding of learning and memory and disorders associated with impairment in these processes. PMID- 27188457 TI - Probing the Neural Correlates of Number Processing. AB - The cognitive and neural mechanisms that enable humans to encode and manipulate numerical information have been subject to an increasing number of experimental studies over the past 25 years or so. Here, I highlight recent findings about how numerical information is neurally coded, focusing on the theoretical implications derived from the most influential theoretical framework in numerical cognition the Triple Code Model. At the core of this model is the assumption that bilateral parietal cortex hosts an approximate number system that codes for the cardinal value of perceived numerals. I will review studies that ask whether or not the numerical coding within this system is invariant to varying input notation, format, or modality, and whether or not the observed parietal activity is number specific over and above the parietal involvement in response-related processes. Extant computational models of numerosity (the number of objects in a set) perception are summarized and related to empirical data from human neuroimaging and monkey neurophysiology. PMID- 27188459 TI - Nonalcoholic fatty liver disease. AB - Nonalcoholic fatty liver disease (NAFLD) is a disorder characterized by excess accumulation of fat in hepatocytes (nonalcoholic fatty liver (NAFL)); in up to 40% of individuals, there are additional findings of portal and lobular inflammation and hepatocyte injury (which characterize nonalcoholic steatohepatitis (NASH)). A subset of patients will develop progressive fibrosis, which can progress to cirrhosis. Hepatocellular carcinoma and cardiovascular complications are life-threatening co-morbidities of both NAFL and NASH. NAFLD is closely associated with insulin resistance; obesity and metabolic syndrome are common underlying factors. As a consequence, the prevalence of NAFLD is estimated to be 10-40% in adults worldwide, and it is the most common liver disease in children and adolescents in developed countries. Mechanistic insights into fat accumulation, subsequent hepatocyte injury, the role of the immune system and fibrosis as well as the role of the gut microbiota are unfolding. Furthermore, genetic and epigenetic factors might explain the considerable interindividual variation in disease phenotype, severity and progression. To date, no effective medical interventions exist that completely reverse the disease other than lifestyle changes, dietary alterations and, possibly, bariatric surgery. However, several strategies that target pathophysiological processes such as an oversupply of fatty acids to the liver, cell injury and inflammation are currently under investigation. Diagnosis of NAFLD can be established by imaging, but detection of the lesions of NASH still depend on the gold-standard but invasive liver biopsy. Several non-invasive strategies are being evaluated to replace or complement biopsies, especially for follow-up monitoring. PMID- 27188458 TI - PFN2, a novel marker of unfavorable prognosis, is a potential therapeutic target involved in esophageal squamous cell carcinoma. AB - BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most aggressively malignant tumors with dismal prognosis. Profilin 2 (PFN2) is an actin-binding protein that regulates the dynamics of actin polymerization and plays a key role in cell motility. Recently, PFN2 have emerged as significant regulators of cancer processes. However, the clinical significance and biological function of PFN2 in ESCC remain unclear. METHODS: PFN2 protein expression was validated by immunohistochemistry (IHC) on tissue microarray from Chinese Han and Kazakh populations with ESCC. The associations among PFN2 expression, clinicopathological features, and prognosis of ESCC were analyzed. The effects on cell proliferation, invasion and migration were examined using MTT and Transwell assays. Markers of epithelial-mesenchymal transition (EMT) were detected by Western blot analysis. RESULTS: Compared with normal esophageal epithelium (NEE), PFN2 protein expression was markedly increased in low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), and ESCC, increased gradually from LGIN to ESCC, and finally reached high grade in HGIN in the Han population. Similarly, PFN2 protein was more overexpressed in ESCC than in NEE in the Kazakh population. The results of Western blot analysis also showed that PFN2 expression was significantly higher in the ESCC tissue than in a matched adjacent non-cancerous tissue. PFN2 expression was positively correlated with invasion depth and lymph node metastasis. High PFN2 expression was significantly correlated with short overall survival (OS) (P = 0.023). Cox regression analysis revealed that PFN2 expression was an independent prognostic factor for poor OS in ESCC. Downregulation of PFN2 inhibited, rather than proliferated, cell invasion and migration, as well as induced an EMT phenotype, including increased expression of epithelial marker E-cadherin, decreased mesenchymal marker Vimentin, Snail, Slug and ZEB1, and morphological changes in ESCC cells in vitro. CONCLUSIONS: Our findings demonstrate that PFN2 has a novel role in promoting ESCC progression and metastasis and portending a poor prognosis, indicating that PFN2 could act as an early biomarker of high-risk population. Targeting PFN2 may offer a promising therapeutic strategy for ESCC treatment. PMID- 27188460 TI - Predicting Unprotected Sex and Unplanned Pregnancy among Urban African-American Adolescent Girls Using the Theory of Gender and Power. AB - Reproductive coercion has been hypothesized as a cause of unprotected sex and unplanned pregnancies, but research has focused on a narrow set of potential sources of reproductive coercion. We identified and evaluated eight potential sources of reproductive coercion from the Theory of Gender and Power including economic inequality between adolescent girls and their boyfriends, cohabitation, and age differences. The sample comprised sexually active African-American female adolescents, ages 15-21. At baseline (n = 715), 6 months (n = 607), and 12 months (n = 605), participants completed a 40-min interview and were tested for semen Y chromosome with polymerase chain reaction from a self-administered vaginal swab. We predicted unprotected sex and pregnancy using multivariate regression controlling for demographics, economic factors, relationship attributes, and intervention status using a Poisson working model. Factors associated with unprotected sex included cohabitation (incidence risk ratio (IRR) 1.48, 95 % confidence interval (1.22, 1.81)), physical abuse (IRR 1.55 (1.21, 2.00)), emotional abuse (IRR 1.31 (1.06, 1.63)), and having a boyfriend as a primary source of spending money (IRR 1.18 (1.00, 1.39)). Factors associated with unplanned pregnancy 6 months later included being at least 4 years younger than the boyfriend (IRR 1.68 (1.14, 2.49)) and cohabitation (2.19 (1.35, 3.56)). Among minors, cohabitation predicted even larger risks of unprotected sex (IRR 1.93 (1.23, 3.03)) and unplanned pregnancy (3.84 (1.47, 10.0)). Adolescent cohabitation is a marker for unprotected sex and unplanned pregnancy, especially among minors. Cohabitation may have stemmed from greater commitment, but the shortage of affordable housing in urban areas could induce women to stay in relationships for housing. Pregnancy prevention interventions should attempt to delay cohabitation until adulthood and help cohabiting adolescents to find affordable housing. PMID- 27188462 TI - Comparing mutation rates under the Luria-Delbruck protocol. AB - Comparison of microbial mutation rates under the Luria-Delbruck protocol is a routine laboratory task. However, execution of this important task has been hampered by the lack of proper statistical methods. Visual inspection or improper use of the t test and the Mann-Whitney test can impair the quality of genetic research. This paper proposes a unified framework for constructing likelihood ratio tests that overcome three important obstacles to the proper comparison of microbial mutation rates. Specifically, algorithms for likelihood ratio tests have been devised that allow for partial plating, differential growth rates and unequal terminal cell population sizes. The new algorithms were assessed by computer simulations. In addition, a strategy for multiple comparison was illustrated by reanalyzing the experimental data from a study of bacterial resistance against tuberculosis antibiotics. PMID- 27188463 TI - Clinicopathological Features of Colorectal Cancer Patients Under the Age of 50: Recent Experience and Case-Control Study of Prognosis in a Japanese Cohort. AB - BACKGROUND/AIMS: The incidence of colorectal cancer (CRC) in young people is increasing, indicating an urgent need for understanding young-onset CRC. This study serves to clarify the characteristics and prognosis of young CRC patients. METHODS: Using a detailed database, various clinicopathological findings including symptoms, family history and prognosis of 70 young CRC patients under 50 years who underwent surgical resection between 2005 and 2011 were compared to 786 old CRC patients over 50 years. For the comparison of prognosis, a matched 1:4 case-control study adjusting for gender, tumor location, tumor differentiation type, and Union For International Cancer Control stage was conducted. RESULTS: The young group had a higher proportion of rectal cancer (51.4 vs. 36.4%, p = 0.004) and a higher positive rate for the Amsterdam criteria II (7.1 vs. 1.9%, p = 0.02) than the old group. There was no significant difference in overall survival (OS) or cancer-specific survival (CSS) between the young and old groups (5-year OS: 84.7 vs. 76.9%, p = 0.18; 5-year CSS: 84.7 vs. 82.8%, p = 0.55). CONCLUSION: This study may add a new perspective to understanding young-onset CRC. The prognosis of young CRC patients was equivalent to that of old CRC patients. PMID- 27188464 TI - Sustainable, Rapid Synthesis of Bright-Luminescent CuInS2-ZnS Alloyed Nanocrystals: Multistage Nano-xenotoxicity Assessment and Intravital Fluorescence Bioimaging in Zebrafish-Embryos. AB - Near-infrared (NIR) luminescent CuInS2-ZnS alloyed nanocrystals (CIZS-NCs) for highly fluorescence bioimaging have received considerable interest in recent years. Owing, they became a desirable alternative to heavy-metal based-NCs and organic dyes with unique optical properties and low-toxicity for bioimaging and optoelectronic applications. In the present study, bright and robust CIZS-NCs have been synthesized within 5 min, as-high-as 230 degrees C without requiring any inert-gas atmosphere via microwave-solvothermal (MW-ST) method. Subsequently, the in vitro and in vivo nano-xenotoxicity and cellular uptake of the MUA functionalized CIZS-NCs were investigated in L929, Vero, MCF7 cell lines and zebrafish-embryos. We observed minimal toxicity and acute teratogenic consequences upto 62.5 MUg/ml of the CIZS-NCs in zebrafish-embryos. We also observed spontaneous uptake of the MUA-functionalized CIZS-NCs by 3 dpf older zebrafish-embryos that are evident through bright red fluorescence-emission at a low concentration of 7.8 MUg/mL. Hence, we propose that the rapid, low-cost, large-scale "sustainable" MW-ST synthesis of CIZS-NCs, is an ideal bio-nanoprobe with good temporal and spatial resolution for rapid labeling, long-term in vivo tracking and intravital-fluorescence-bioimaging (IVBI). PMID- 27188461 TI - Mediator subunit Med12 contributes to the maintenance of neural stem cell identity. AB - BACKGROUND: The RNA polymerase II transcriptional Mediator subunit Med12 is broadly implicated in vertebrate brain development, and genetic variation in human MED12 is associated with X-linked intellectual disability and neuropsychiatric disorders. Although prior studies have begun to elaborate the functional contribution of Med12 within key neurodevelopmental pathways, a more complete description of Med12 function in the developing nervous system, including the specific biological networks and cellular processes under its regulatory influence, remains to be established. Herein, we sought to clarify the global contribution of Med12 to neural stem cell (NSC) biology through unbiased transcriptome profiling of mouse embryonic stem (ES) cell-derived NSCs following RNAi-mediated Med12 depletion. RESULTS: A total of 240 genes (177 up, 73 down) were differentially expressed in Med12-knockdown versus control mouse NS-5 (mNS 5) NSCs. Gene set enrichment analysis revealed Med12 to be prominently linked with "cell-to-cell interaction" and "cell cycle" networks, and subsequent functional studies confirmed these associations. Targeted depletion of Med12 led to enhanced NSC adhesion and upregulation of cell adhesion genes, including Syndecan 2 (Sdc2). Concomitant depletion of both Sdc2 and Med12 reversed enhanced cell adhesion triggered by Med12 knockdown alone, confirming that Med12 negatively regulates NSC cell adhesion by suppressing the expression of cell adhesion molecules. Med12-mediated suppression of NSC adhesion is a dynamically regulated process in vitro, enforced in self-renewing NSCs and alleviated during the course of neuronal differentiation. Accordingly, Med12 depletion enhanced adhesion and prolonged survival of mNS-5 NSCs induced to differentiate on gelatin, effects that were bypassed completely by growth on laminin. On the other hand, Med12 depletion in mNS-5 NSCs led to reduced expression of G1/S phase cell cycle regulators and a concordant G1/S phase cell cycle block without evidence of apoptosis, resulting in a severe proliferation defect. CONCLUSIONS: Med12 contributes to the maintenance of NSC identity through a functionally bipartite role in suppression and activation of gene expression programs dedicated to cell adhesion and G1/S phase cell cycle progression, respectively. Med12 may thus contribute to the regulatory apparatus that controls the balance between NSC self renewal and differentiation, with important implications for MED12-linked neurodevelopmental disorders. PMID- 27188465 TI - Agmatine Modulation of Noradrenergic Neurotransmission in Isolated Rat Blood Vessels. AB - Agmatine, a vasoactive metabolite of L-arginine, is widely distributed in mammalian tissues including blood vessels. Agmatine binding to imidazoline and alpha2-adrenoceptors induces a variety of physiological and pharmacological effects. We investigated the effect of agmatine on contractile responses of the rat pulmonary artery and portal vein induced by electrical stimulation of perivascular nerves and by exogenous adrenergic substances. Experiments were performed on isolated segments of rat main pulmonary artery and its extralobular branches, and portal vein suspended in organ bath containing modified Krebs bicarbonate solution and connected to a force-displacement transducer for isometric tension recording. Electrical field stimulation (EFS) produced tetrodotoxin-sensitive contractile responses of pulmonary artery and portal vein. Besides the well known vasorelaxant actions, we found that agmatine also produced a concentration-dependent inhibition of neurogenic contractions induced by EFS in pulmonary arteries; however, the agmatine treatment did not influence the responses to exogenous noradrenaline. The inhibitory effect on EFS-induced contractions was not abolished by the alpha2-adrenoceptor antagonist rauwolscine. In portal vein, in contrast, agmatine increased spontaneous mechanical contractions and enhanced the contractions induced by EFS. The results suggest that agmatine can significantly influence vascular function of pulmonary arteries and portal veins by modulating sympathetically mediated vascular contractions by pre- and postsynaptic mechanisms. PMID- 27188466 TI - Improved Race Times in Marathoners Older than 75 Years in the Last 25 Years in the World's Largest Marathons. AB - Performance trends of elite marathoners are well investigated. However, performance of elderly marathoners (> 75 years) competing in the world's largest city marathons is not well-known. We examined marathon race data of 1,691 marathon finishes (i.e. 218 women and 1,473 men) competing between 1990 and 2014 in 5-year age groups 75-79, 80-84, 85-89, and 95-99 years in four races (Berlin, New York, Chicago and Boston) of the 'World Marathon Majors'. The number of female (r2 = 0.50, P < 0.0001) and male (r2 = 0.88, P < 0.0001) finishers increased significantly across years. The number of women (r2 = 0.36, P = 0.0019) and men (r2 = 0.88, P < 0.0001) in age group 75-79 years increased. In age group 80-84 years, the number of women (r2 = 0.36, P = 0.0111) and men (r2 = 0.54, P < 0.0001) also increased. In age groups 85-89 to 95-99 years, however, the number of female and male finishers remained unchanged. Across years, women (r2 = 0.26, P = 0.0090) and men (r2 = 0.31, P = 0.0035) reduced their race times. Women and men in age group 75-79 years improved race times. In age groups 80-84 to 90-94 years, women and men were not able to reduce race times. In summary, participation increased and performance improved in female and male marathoners competing in age groups 75-79 to 95-99 years where the largest increases in participation and the largest improvements in performance were found in women and men in age group 75-79 years. PMID- 27188467 TI - Ca2+ Movement Induced by Deltamethrin in PC3 Human Prostate Cancer Cells. AB - This study explored the effect of deltamethrin, a pesticide, on intracellular free Ca2+ concentration ([Ca2+]i) in PC3 human prostate cancer cells. Deltamethrin at concentrations between 5 MUM and 20 MUM evoked [Ca2+]i rises in a concentration-dependent manner. This Ca2+ signal was inhibited by 22% by removal of extracellular Ca2+. Nifedipine, econazole, and SKF96365 also inhibited the Ca2+ signal. Treatment with the endoplasmic reticulum Ca2+ pump inhibitor 2,5-di tert-butylhydroquinone (BHQ) in Ca2+-free medium nearly abolished deltamethrin induced [Ca2+]i rises. Treatment with deltamethrin also inhibited most of BHQ induced [Ca2+]i rises. Inhibition of phospholipase C (PLC) with U73122 failed to alter deltamethrin-evoked [Ca2+]i rises. Deltamethrin killed cells at concentrations of 20-100 MUM in a concentration-dependent fashion. Chelation of cytosolic Ca2+ with 1,2-bis (2-aminophenoxy) ethane-N, N, N', N'-tetraacetic acid/acetoxymethyl ester (BAPTA/AM) did not prevent deltamethrin's cytotoxicity. Together, in PC3 human prostate cancer cells, deltamethrin induced [Ca2+]i rises that involved Ca2+ entry through store-operated Ca2+ channels and PLC-independent Ca2+ release from the endoplasmic reticulum. Deltamethrin induced cytotoxicity in a Ca2+-independent manner. PMID- 27188469 TI - Improvement of Acetylcholine-Induced Vasodilation by Acute Exercise in Ovariectomized Hypertensive Rats. AB - Postmenopause is associated with the development of cardiovascular disease, such as hypertension. However, limited information is available regarding effects of exercise on cardiovascular responses and its underlying mechanisms in the simultaneous postmenopausal and hypertensive status. We aimed to investigate whether acute exercise could enhance vasodilation mediated by acetylcholine (ACh) and sodium nitroprusside (SNP) in ovariectomized hypertensive rats. The fifteen week-old female spontaneously hypertensive rats (SHR) were bilaterally ovariectomized, at the age of twenty-four weeks, and randomly divided into sedentary (SHR-O) and acute exercise (SHR-OE) groups. Age-matched WKY rats were used as the normotensive control group. The SHR-OE group ran on a motor-driven treadmill at a speed of 24 m/min for one hour in a moderate-intensity program. Following a single bout of exercise, rat aortas were isolated for the evaluation of the endothelium-dependent (ACh-induced) and endothelium-independent (SNP induced) vasodilation by the organ bath system. Also, the serum levels of oxidative stress and antioxidant activities, including malondialdehyde (MDA), superoxide dismutase (SOD), and catalase, were measured after acute exercise among the three groups. We found that acute exercise significantly enhanced the ACh-induced vasodilation, but not the SNP-induced vasodilation, in ovariectomized hypertensive rats. This increased vasodilation was eliminated after the inhibition of nitric oxide synthase (NOS). Also, the activities of SOD and catalase were significantly increased after acute exercise, whereas the level of MDA was comparable among the three groups. These results indicated that acute exercise improved the endothelium-dependent vasodilating response to ACh through the NOS-related pathway in ovariectomized hypertensive rats, which might be associated with increased serum antioxidant activities. PMID- 27188468 TI - The Role of Gastrodin on Hippocampal Neurons after N-Methyl-D-Aspartate Excitotoxicity and Experimental Temporal Lobe Seizures. AB - Tian ma (Gastrodia elata, GE) is an ancient Chinese herbal medicine that has been suggested to be effective as an anticonvulsant and analgesic, and to have sedative effects against vertigo, general paralysis, epilepsy and tetanus. The primary active ingredient isolated from GE is termed gastrodin, which is the glucoside of 4-hydroxybenzyl alcohol (4-HBA). Gastrodin can abolish hypoxia-, glutamate- and N-methyl-D-aspartate (NMDA) receptor-induced toxicity in primary culture of rat cortical neurons, and reduces seizure severity in seizure sensitive gerbils. We evaluated the effect of gastrodin on NMDA excitotoxicity in hippocampal slice cultures (HSCs) with propidium iodide (PI) fluorescence measurement. We also evaluated the effects of gastrodin for treating active in vivo temporal lobe seizures induced by lithium/pilocarpine. Seizure severity, time span to seizure onset, mortality rate and hippocampal histology for survivors were compared. The effect of gastrodin was evaluated for treating in vitro seizures induced by Mg2+-free medium in hippocampal slices. Frequencies and amplitudes of epileptiform discharges were compared. The effect of gastrodin on synaptic transmission was evaluated on hippocampal CA1 Schaffer collaterals. Application of 25 MUM gastrodin significantly suppressed NMDA excitotoxicity in CA3 but not in CA1 hippocampus and dentate gyrus. Intraventricular gastrodin accelerated seizure onset for 12 min after intraperitoneal pilocarpine injection (P = 0.051). Three of five rats (60%) in the gastrodin group, and three of four (75%) in the dimethyl sulfoxide (DMSO) group died within 3 days after status epilepticus (SE). Gastrodin also failed to inhibit epileptiform discharges in hippocampal slices induced by Mg2+-free medium, believed to be NMDA receptor mediated spontaneous activity. The frequencies of the spontaneous epileptiform discharges were similar under treatments with 25 MUM gastrodin, 200 MUM gastrodin and DMSO. For the evaluation of gastrodin on synaptic transmission, application of DMSO, 25 MUM or 200 MUM gastrodin had no significant effect on excitatory postsynaptic potential (EPSP) slopes. Gastrodin at 200 MUM decreased paired-pulse facilitation (PPF) from 1.23 +/- 0.04 to 1.12 +/- 0.04 (P = 0.002). In conclusion, gastrodin failed to suppress in vivo and in vitro seizures in our study. Gastrodin showed no effect on hippocampal Schaffer collateral EPSP. These findings suggest that gastrodin does not interact with ionotropic glutamate receptors to inhibit NMDA receptor-facilitated seizures. However, gastrodin showed protective effects against NMDA toxicity on cultured hippocampal slices. Nevertheless, gastrodin is still a potential neuroprotective agent against NMDA excitotoxicity, with potential benefits for stroke and patients with epilepsy. PMID- 27188472 TI - Increasing prevalence of scarlet fever in China. PMID- 27188473 TI - The Ethics of Gender in Pediatric Reconstructive Urology. PMID- 27188470 TI - Pre- and Post-Race Hydration Status in Hyponatremic and Non-Hyponatremic Ultra Endurance Athletes. AB - The monitoring of body mass (BM), plasma sodium concentration ([Na+]) and urinary specific gravity (Usg) are commonly used to help detect and prevent over- or dehydration in endurance athletes. We investigated pre-and post-race hydration status in 113 amateur 24-h ultra-runners, 100-km ultra-runners, multi-stage mountain bikers and 24-h mountain bikers, which drank ad libitum without any intervention and compared results of hyponatremic and non-hyponatremic finishers. On average, pre-race plasma [Na+] and both pre- and post-race levels of Usg and BM were not significantly different between both groups. However, nearly 86% of the post-race hyponatremic (exercise-associated hyponatremia, EAH) and 68% of the normonatremic (non-EAH) ultra-athletes probably drank prior the race greater volumes than their thirst dictated regarding to individual pre-race Usg levels. Fluid intake during the race was equal and was not related to plasma [Na+], Usg or BM changes. A significant decrease in post-race plasma [Na+], BM and an increasement in post-race Usg was observed in EAH and non-EAH finishers. Moreover, pre-race plasma [Na+] was inversely associated with post-race percentage change in plasma [Na+], and pre-race Usg and urinary [Na+] with percentage change in Usg in both groups with and without post-race EAH. Thirteen (11.5%) finishers developed post-race EAH (plasma [Na+] < 135 mM). The incidence of EAH in ultra-endurance athletes competing in the Czech Republic was higher than reported previously. PMID- 27188477 TI - Gleason Score 7: When Qualitative Change Becomes Quantitative Change. PMID- 27188476 TI - External Evaluation of a Novel Prostate Cancer Risk Calculator (ProstateCheck) Based on Data from the Swiss Arm of the ERSPC. AB - PURPOSE: We externally validated a novel prostate cancer risk calculator based on data from the Swiss arm of the ERSPC and assessed whether the risk calculator (ProstateCheck) is superior to the PCPT-RC and SWOP-RC in an independent Swiss cohort. MATERIALS AND METHODS: Data from all men who underwent prostate biopsy at an academic tertiary care center between 2004 and 2012 were retrospectively analyzed. The probability of having any prostate cancer or high grade prostate cancer (Gleason score 7 or greater) on prostate biopsy was calculated using the ProstateCheck. Risk calculator performance was assessed using calibration and discrimination, and additionally compared with the PCPT-RC and SWOP-RC by decision curve analyses. RESULTS: Of 1,615 men 401 (25%) were diagnosed with any prostate cancer and 196 (12%) with high grade prostate cancer. Our analyses of the ProstateCheck-RC revealed good calibration in the low risk range (0 to 0.4) and moderate overestimation in the higher risk range (0.4 to 1) for any and high grade prostate cancer. The AUC for the discrimination of any prostate cancer and high grade prostate cancer was 0.69 and 0.72, respectively, which was slightly but significantly higher compared to the PCPT-RC (0.66 and 0.69, respectively) and SWOP-RC (0.64 and 0.70, respectively). Decision analysis, taking into account the harms of transrectal ultrasound measurement of prostate volume, showed little benefit for ProstateCheck-RC, with properties inferior to those of the PCPT-RC and SWOP-RC. CONCLUSIONS: Our independent external evaluation revealed moderate performance of the ProstateCheck-RC. Its clinical benefit is limited, and inferior to that of the PCPT-RC and SWOP-RC. PMID- 27188478 TI - Fitness consequences of artificial selection on relative male genital size. AB - Male genitalia often show remarkable differences among related species in size, shape and complexity. Across poeciliid fishes, the elongated fin (gonopodium) that males use to inseminate females ranges from 18 to 53% of body length. Relative genital size therefore varies greatly among species. In contrast, there is often tight within-species allometric scaling, which suggests strong selection against genital-body size combinations that deviate from a species' natural line of allometry. We tested this constraint by artificially selecting on the allometric intercept, creating lines of males with relatively longer or shorter gonopodia than occur naturally for a given body size in mosquitofish, Gambusia holbrooki. We show that relative genital length is heritable and diverged 7.6 8.9% between our up-selected and down-selected lines, with correlated changes in body shape. However, deviation from the natural line of allometry does not affect male success in assays of attractiveness, swimming performance and, crucially, reproductive success (paternity). PMID- 27188479 TI - Major adverse cardiovascular events with basal insulin peglispro versus comparator insulins in patients with type 1 or type 2 diabetes: a meta-analysis. AB - BACKGROUND: To identify possible differences in cardiovascular (CV) risk among different insulin therapies, we performed pre-specified meta-analyses across the clinical program for basal insulin peglispro (BIL), in patients randomized to treatment with BIL or comparator insulin [glargine (IG) or NPH]. METHODS: One phase 2 (12-week) and 6 phase 3 (26 to 78-week) randomized studies of BIL compared to IG or NPH, in patients with type 1 or type 2 diabetes, were included. The participants were diverse with respect to demographics, baseline glycemic control, and concomitant disease or medications, but treatment groups were comparable in each study. For any potential CV or neurovascular event, relevant medical information was provided to a blinded external clinical events committee (C5Research, Cleveland Clinic, Cleveland, OH, USA) for adjudication. Cox regression analysis was used to compare treatment groups. The primary endpoint was a composite of adjudicated MACE+ [CV death, myocardial infarction (MI), stroke, or hospitalization for unstable angina]. RESULTS: The pooled population included 5862 patients in the safety evaluation, with randomization to BIL:IG:NPH of 3578:2072:212. Mean age was 54.1 years, 27 % had type 1 diabetes, 56 % were male, and 88 % were white. Baseline demographic and clinical characteristics, including use of statins or other lipid-lowering drugs, were comparable between BIL and comparators. A total of 83 patients experienced at least 1 MACE+ and 70 patients experienced at least 1 MACE (CV death, MI, or stroke). Overall, there were no treatment-associated differences in time to MACE+ [hazard ratio (HR) for BIL versus comparator insulin (95 % CI): 0.82 (0.53-1.27)] or MACE [0.83 (0.51 1.33)]. In 4297 patients with type 2 diabetes, there were 71 MACE+ events [HR: 1.02 (95 % CI: 0.63-1.65), p = 0.94]. In 1565 patients with type 1 diabetes, there were only 12 MACE+ [0.24 (0.07-0.85), p = 0.027]. There were no differences in all-cause death between BIL and comparators. Sub-group analyses did not identify any sub-population with increased risk with BIL versus comparator insulins. CONCLUSIONS: Treatment with BIL versus comparator insulin in patients with type 1 diabetes or type 2 diabetes was not associated with increased risk for major CV events in the studies analyzed. PMID- 27188480 TI - The structure and in situ synthesis investigation of isomorphic mononuclear molecular metal phenylphosphonates. AB - We describe a fast and effective synthesis for molecular metal phosphonates. Isomorphic compounds [M(ii)(HO3PPh)2(H2O3PPh)2(H2O)2] (M = Mn (1), Co (2), Ni (3); Ph = C6H5) were obtained by grinding. The complexes are mononuclear compounds containing neutral and monodeprotonated phenylphosphonic acid and water as ligands. The crystal structures were determined using powder X-ray diffraction (PXRD) data and validated by extended X-ray absorption fine structure (EXAFS) data. Combined synchrotron XRD measurements and Raman spectroscopy were conducted for investigating the reactions in situ. Based on these data, the intermediates were characterized and the formation mechanism was derived. PMID- 27188474 TI - Treatment of Patients with Positive Margins after Partial Nephrectomy. PMID- 27188482 TI - [Further understanding on myocardial damage in the early stage post severe burn and its clinical significance]. AB - A series of studies demonstrated that myocardial damage and cardiac dysfunction occurs immediately following severe burn, even before significant reduction in blood volume due to increased capillary permeability. Such myocardial damage and cardiac dysfunction leads to cardiac deficiency, and it is a precipitating factor for burn shock and ischemic/hypoxic injury. In recent years, many experimental and clinical studies elucidated the pathogenesis and confirmed the clinical importance of prevention and treatment of"shock heart"in the early stage post severe burn. PMID- 27188481 TI - Perinatal outcomes of vacuum assisted versus cesarean deliveries for prolonged second stage of delivery at term. AB - INTRODUCTION: To compare perinatal outcomes of interventions for prolonged second stage of labor. MATERIALS AND METHODS: Retrospective cohort study, in a single, university-affiliate, medical center (2007-2014). Eligibility: singleton gestations at term, diagnosed with prolonged second stage of labor and head station of S + 1 and lower. We compared perinatal outcomes of cesarean deliveries (CD) with vacuum assisted deliveries (VAD). RESULTS: Of 62 102 deliveries, 3449 (5.6%) were eligible: 356 (10.3%) underwent CD and 3093 (89.7%) underwent VAD. The rate of five-minute Apgar scores <7 was higher in the CD group as well as rates of NICU admission, neonatal asphyxia and composite neonatal adverse outcome. After adjusting for different confounders, CD was associated with adverse neonatal composite outcome (aOR 1.57, 95% CI 1.21-2.05, p = 0.001) and VAD with cephalhematoma (aOR 4.06, 95% CI 2.64-6.25, p < 0.001). No other differences were found between the groups with regards to other traumatic outcomes. CONCLUSION: Our data suggests that in deliveries complicated by prolonged second stage, CD yield poorer neonatal outcome than VAD, with no apparent major difference in traumatic composite outcome. PMID- 27188471 TI - Adherence to Alternative Healthy Eating Index in relation to depression and anxiety in Iranian adults. AB - Earlier studies have shown a protective association between adherence to healthy eating guidelines and mental disorders in Western nations; however, data in this regard are limited from the understudied region of Middle East. We examined the association between adherence to healthy eating guidelines, as measured by Alternative Healthy Eating Index (AHEI)-2010, and prevalence of anxiety and depression in a large sample of Iranian adults. In this cross-sectional study, data on dietary intakes of 3363 adult participants were collected using a validated dish-based 106-item semi-quantitative FFQ. Adherence to healthy eating was quantified using AHEI-2010, as suggested by earlier publications. The Iranian validated version of Hospital Anxiety and Depression Scale was used to assess anxiety and depression in study participants. Data on other covariates were gathered using a pre-tested questionnaire. Overall, the prevalence of anxiety and depression was 15.2 % (males 10.8 % and females 18.3 %) and 30.0 % (males 22.9 % and females 35.1 %), respectively. After controlling for potential confounders, those in the top quartile of AHEI-2010 had a 49 % lower chance of anxiety (OR 0.51; 95 % CI 0.35, 0.72) and a 45 % lower odds of depression (OR 0.55; 95 % CI 0.42, 0.72), compared with those in the bottom quartile. Stratified analysis by sex revealed that women in the highest categories of AHEI-2010 had a 49 % lower odds of having anxiety and depression, after adjustment for confounders, but no significant association was found in men. In addition, among individuals who were 40 years old or younger, those with high adherence to AHEI-2010 were 58 and 51 % less likely to have anxiety and depression, compared with those with less adherence. Adherence to healthy eating was inversely associated with a lower chance of anxiety and depression in Iranian adults. Prospective studies are required to confirm these associations in Middle-Eastern populations. PMID- 27188483 TI - [Retrospective study on the myocardial damage of 252 patients with severe burn]. AB - OBJECTIVE: To retrospectively analyze the risk factors and clinical manifestations of myocardial damage of patients with severe burn in order to provide evidence for its prevention and treatment. METHODS: Two hundred and fifty two patients with severe burn admitted to 5 burn centers from January 2010 to June 2015, conforming to the study criteria, were treated in accordance with the fluid resuscitation formula of the Third Military Medical University. According to the creatine kinase isoenzyme-MB (CK-MB) level before treatment on admission, patients were divided into non-myocardial damage group (n=118, CK-MB level less than 75 U/mL) and myocardial damage group (n=134, CK-MB level higher than or equal to 75 U/mL). Data of patients in two groups were collected and evaluated such as gender, age, body mass, number of patients with chemical burn, admission time after injury, total burn area, full-thickness burn area, number of patients with inhalation injury, levels of haemoglobin, hematocrit, and blood lactate on admission and at post injury hour (PIH) 24 and 48, volumes of urine output and fluid input at PIH 24 and 48, levels of creatinine, urea nitrogen, total bile acid, diamine oxidase on admission and at PIH 24 and 48, and mortality. Furthermore, patients were divided into three groups, i. e. less than 50% total body surface area (TBSA) group (n=110), larger than or equal to 50% TBSA and less than 80% TBSA group (n=83), and larger than or equal to 80% TBSA group (n=59) according to the total burn area, and the incidence rates of myocardial damage in patients of three groups were recorded. Data were processed with chi-square test, t test, Wilcoxon test, analysis of variance for repeated measurement, and the values of P were adjusted by Bonferroni. Basic data of 252 patients were processed with binary logistic regression analysis. Receiver operating characteristic curve of total burn area of 252 patients was drawn to predict myocardial damage. RESULTS: (1) There were no statistically significant differences in age, body mass, number of patients with chemical burn, number of patients with inhalation injury, and full-thickness burn area between two groups (with t values respectively 0.20 and 0.31, chi(2) values respectively 0.49 and 4.10, Z=1.42, P values above 0.05). There were statistically significant differences in gender, admission time after injury, and total burn area of patients between two groups (chi(2)=5.00, with t values respectively 2.44 and 3.13, P<0.05 or P<0.01). (2) Gender, admission time after injury, and total burn area were independent risk factors related to myocardial damage in the patients (with odds ratios respectively 2.608, 3.620, and 1.030; 95% confidence intervals respectively 1.315-5.175, 1.916-6.839, and 1.011-1.049; P values below 0.01). (3) The incidence rates of myocardial damage of patients in less than 50% TBSA group, larger than or equal to 50% TBSA and less than 80% TBSA group, and larger than or equal to 80% TBSA group were 38.2% (42/110), 54.2% (45/83), and 61.0% (36/59) respectively, and there was statistically significant difference among them (chi(2)=9.46, P<0.05). (4) The total area under receiver operating characteristic curve of total burn area to predict myocardial damage of 252 patients was 0.706 (with 95% confidence interval 0.641-0.772, P<0.01), and 51.5% TBSA was chosen as the optimal threshold value, with sensitivity of 62.6% and specificity of 65.3%. (5) Compared with those in non-myocardial damage group, except the levels of haemoglobin and hematocrit at PIH 48 (with t values respectively -0.76 and -0.61, P values above 0.05), the levels of haemoglobin, hematocrit, and blood lactate of patients in myocardial damage group were significantly increased at each time point (with t values from -2.80 to -2.06, P<0.05 or P<0.01). Compared with those in non-myocardial damage group, the volume of urine output of patients was significantly declined (with t values respectively 2.05 and 3.68, P<0.05 or P<0.01), while the volume of fluid input of patients was not obviously changed in myocardial damage group at PIH 24 and 48 (with t values respectively 1.01 and 1.08, P values above 0.05). (6) Compared with those in non-myocardial damage group, the level of creatinine of patients was significantly increased on admission and at PIH 24 and 48 (with Z values from -2.91 to -1.99, P<0.05 or P<0.01), the level of urea nitrogen of patients was only significantly increased at PIH 24 and 48 (with t values respectively -4.75 and -5.24, P values below 0.01), the level of total bile acid of patients was not obviously changed on admission and at PIH 24 and 48 (with t values from -0.81 to -0.20, P values above 0.05), and the level of diamine oxidase of patients was only significantly increased on admission and PIH 24 in myocardial damage group (with t values respectively -3.97 and -2.02, P<0.05 or P<0.01). (7) Compared with that in myocardial damage group, the mortality of patients in non-myocardial damage group was significantly declined (chi(2)=5.81, P<0.05). CONCLUSIONS: Patients with severe burn have high incidence of myocardial damage, which may be predicted by total burn area. Severely burned patients with myocardial damage are more likely to suffer from decline of effective circulating volume, tissue oxygenation disorders, and damage in other organs in shock stage. PMID- 27188487 TI - [Advances in the research of early goal-directed therapy in severe sepsis and septic shock]. AB - Nowadays, severe infection has become one of the common problems in clinic. The morbidity of severe sepsis and septic shock is increasing, which becomes a big threat to patients with burn wounds or chronic diseases. It has become a key subject about how to cure severe sepsis and septic shock. In recent years, mortality of patients in such condition has declined slightly, which might be attributed to the application of early goal-directed therapy (EGDT) in certain degree. This article reviews application of EGDT in severe sepsis and septic shock, in order to analyze its effectiveness and boundedness, as well as predict its development. PMID- 27188485 TI - [Effects of extracellular heat shock protein 70 on intestinal immune function of rats with severe scald injury]. AB - OBJECTIVE: To explore the change in the expression of extracellular heat shock protein 70 (eHSP70) and interleukin 2 (IL-2) and their correlation in intestine of rats with severe scald injury, and to observe the effects of eHSP70 on CD3(+) T lymphocytes in Peyer's patch of intestine in rats with severe scald injury in vitro. METHODS: (1) Sixty male SD rats were divided into normal control group (NC, n=10, only anesthetized) and scald group (S, n=50) according to the random number table. Rats in scald group were inflicted with 30% total body surface area full-thickness scald on the back. Ten rats from group NC immediately after anesthetization and 10 rats from group S at post injury hour (PIH) 3, 6, 12, 24, 48 were sacrificed to harvest their small intestines. The expressions of eHSP70 and IL-2 were determined with enzyme-linked immunosorbent assay (ELISA), and their correlation was analyzed. (2) Another 2 male SD rats were inflicted with the same injury as above. At PIH 12, CD3(+) T lymphocytes in Peyer's patch of small intestine were isolated and cultured with RPMI 1640 nutrient solution containing 10% fetal bovine serum. Cells were divided into blank control group (BC) and 5, 10, 20 MUg/mL eHSP70 groups according to the random number table, with 6 wells in each group. Cells in group BC didn't receive any other treatment, while cells in the latter three groups were treated with corresponding mass concentration of recombinant rat eHSP70. After being cultured for 48 hours, the proportions of Th1 and Th2 in CD3(+) T lymphocytes, and the apoptosis rate of CD3(+) T lymphocytes were detected with flow cytometer, while the expressions of IL-2 and IL-10 in culture supernatant of cells were determined with ELISA. The cell experiments were repeated for 10 times. Data were processed with one-way analysis of variance, Kruskal-Wallis rank sum test, SNK-q test, and Pearson correlation analysis. RESULTS: (1) Compared with those in group NC [(1 278+/-135) and (48.6+/-4.9) ng/mg], the levels of eHSP70 [(728+/-93), (412+/-31), (314+/ 21), (528+/-40), (1 028+/-97) ng/mg] and IL-2 [(38.6+/-2.3), (32.3+/-1.0), (25.3+/-3.6), (33.9+/-4.1), (44.3+/-2.6) ng/mg] in intestine of rats in group S obviously decreased at PIH 3, 6, 12, 24, 48 (with q values from 3.48 to 5.32, P values below 0.05), reaching the nadir both at PIH 12, with a significantly positive correlation between the level of IL-2 and the level of eHSP70 (r=0.920, P<0.01). (2) Compared with those in group BC [(8.6+/-1.1)% and (3.75+/-0.45)%], the proportion of Th1 obviously increased [(11.3+/-2.1)%, (15.7+/-1.8)%, (10.8+/ 1.5)%, with q values from 2.97 to 4.57, P values below 0.05], while the proportion of Th2 obviously decreased [(2.39+/-0.38)%, (1.05+/-0.23)%, (2.67+/ 0.26)%, with q values from 2.48 to 4.32, P values below 0.05] in CD3(+) T lymphocytes of rats in 5, 10, 20 MUg/mL eHSP70 groups. Compared with those in group BC [(34.3+/-2.2)% and (254+/-16) pg/mL], the apoptosis rate of CD3(+) T lymphocytes obviously decreased [(26.1+/-2.6)%, (20.7+/-1.5)%, (31.5+/-2.4)%, with q values from 3.47 to 4.95, P values below 0.05], while the level of IL-2 obviously increased [(417+/-22), (587+/-19), (307+/-27) pg/mL, with q values from 3.02 to 4.98, P values below 0.05] in culture supernatant of CD3(+) T lymphocytes of rats in 5, 10, 20 MUg/mL eHSP70 groups. There was no significant difference in the level of IL-10 in culture supernatant of CD3(+) T lymphocytes of rats among the four groups (F=2.12, P>0.05). CONCLUSIONS: The expressions of eHSP70 and IL-2 in intestine of rats are decreased after severe scald, with a obviously positive correlation between them. eHSP70 can promote the differentiation of CD3(+) T lymphocytes in Th1 orientation, decrease the apoptosis rate of the cells, and promote the release of IL-2 of cells in Peyer's patch of intestine in rats with severe scald injury in vitro. PMID- 27188486 TI - [Efficacy of fenofibrate for hepatic steatosis in rats after severe burn]. AB - OBJECTIVE: To observe the efficacy of fenofibrate for hepatic steatosis in rats after severe burn. METHODS: Twenty-seven male SD rats were divided into sham injury group, burn group, and burn+ fenofibrate group according to the random number table, with 9 rats in each group. Rats in sham injury group were sham injured on the back by immersing in 37 C warm water for 15 s and then remained without other treatment. Rats in burn group and burn+ fenofibrate group were inflicted with 30% total body surface area full-thickness scald (hereinafter referred to as burn) on the back by immersing in 98 C hot water for 15 s, and then they were intraperitoneally injected with lactated Ringer's solution at post injury hour (PIH) 1. From PIH 24 to post injury day (PID) 8, rats in burn+ fenofibrate group were treated with fenofibrate in the dose of 80 mg.kg(-1).d( 1), while those in burn group were treated with equivalent volume of saline. (1) Three rats of each group were respectively selected on PID 4, 6, and 8 for the collection of inferior vena caval blood samples. Serum content of total cholesterol (TC), triglyceride (TG), free fatty acid (FFA), high density lipoprotein (HDL), and low density lipoprotein (LDL) was determined with fully automatic biochemical analyzer. Body mass of each rat was measured immediately after blood sampling, and then rats were sacrificed to collect liver tissue for weighing wet mass. The ratio of wet mass of liver tissue to body mass (liver index) was calculated. Meanwhile, gross observation of liver was performed. (2) One liver tissue sample was harvested from each rat at each time point to observe histopathologic changes with HE staining. One liver tissue slice of each rat at each time point was collected to evaluate degree of hepatic steatosis, and the number of rats in each group in each grade of hepatic steatosis was recorded. Measurement data were processed with analysis of variance of factorial design and SNK test, and enumeration data were processed with Kruskal-Wallis test and Nemenyi test. RESULTS: (1) The content of TC, TG, FFA, and HDL of rats in burn group on PID 4 was obviously different from that in sham injury group (with P values below 0.05). Compared with that in burn group, the content of TC, TG, and FFA of rats was significantly decreased (with P values below 0.05), while the content of HDL of rats was not obviously changed in burn+ fenofibrate group on PID 4 (P>0.05). There were no obvious differences in the content of LDL of rats among 3 groups on PID 4 (with P values above 0.05). The content of TC, TG, and HDL of rats in burn group on PID 6 was obviously different from that in sham injury group (with P values below 0.05). Compared with that in burn group, the content of TC and TG of rats was significantly decreased (with P values below 0.05), while the content of HDL of rats was significantly increased in burn+ fenofibrate group on PID 6 (P<0.05). There were no obvious differences in the content of FFA and LDL of rats among 3 groups on PID 6 (with P values above 0.05). The content of TC and HDL of rats in burn group on PID 8 was obviously different from that in sham injury group (with P values below 0.05). Compared with that in burn group, the content of TC of rats was significantly decreased (P<0.05), while the content of HDL of rats was not obviously changed in burn+ fenofibrate group on PID 8 (P>0.05). There were no obvious differences in content of TG, FFA, and LDL of rats among 3 groups on PID 8 (with P values above 0.05). (2) The texture of liver tissue of rats in burn+ fenofibrate group at each time point was tender and soft, without oil or fat on the section, which was close to the gross condition of liver of rats in sham injury group. Dark yellow plaque scattered on the surface of liver tissue of rats in burn group at each time point with oil and fat on the section, which was especially obvious on PID 6. There was no obvious difference in liver index of rats among 3 groups on PID 4 (F=1.63, P>0.05). On PID 6 and 8, the liver indexes of rats in sham injury group, burn group, and burn+ fenofibrate group were 0.0416+/-0.0016, 0.0533+/-0.0054, and 0.0370+/-0.0069; 0.0423+/-0.0034, 0.0624+/-0.0005, and 0.0444+/-0.0042 respectively. The liver indexes of rats in burn group on PID 6 and 8 were significantly higher than those in the other two groups (with P values below 0.05). There were no obvious differences in the liver indexes of rats between burn+ fenofibrate group and sham injury group on PID 6 and 8 (with P values above 0.05). (3) The liver tissue structure of rats in sham injury group was normal at each time point. Hepatic steatosis of rats in burn group at each time point appeared microvesicular and disperse, which was especially obvious on PID 6. Mild hepatic steatosis was observed in rats of burn+ fenofibrate group on PID 4, and then the structure of liver tissue gradually recovered to normal level from PID 6 on. The degree of hepatic steatosis of rats in sham injury group was 0 grade. One rat in I grade, 1 rat in II grade, and 7 rats in III grade were observed in hepatic steatosis of rats in burn group. Three rats in 0 grade, 4 rats in I grade, and 2 rats in II grade were observed in hepatic steatosis of rats in burn+ fenofibrate group. The degree of hepatic steatosis of rats in burn group was more severe than that in the other two groups (with chi(2) values respectively 56.25 and 162.44, P values below 0.05). The degree of hepatic steatosis of rats in burn+ fenofibrate group was more severe than that in sham injury group (chi(2)=27.51, P<0.05). CONCLUSIONS: Fenofibrate can ameliorate the dyslipidemia of severely burned rat, and it can alleviate the degree of hepatic steatosis in certain degree. PMID- 27188484 TI - [Effects of ulinastatin on immune function of spleen in severely burned rats and its mechanism]. AB - OBJECTIVE: To observe the effects of ulinastatin on immune function of splenic CD4(+) T lymphocytes and CD4(+) CD25(+) regulatory T lymphocytes (Tregs) and content of high mobility group box 1 (HMGB1) in peripheral blood of severely burned rats, and to analyze the possible mechanisms. METHODS: Ninety-six male SD rats were divided into sham injury group, burn group, and ulinastatin group according to the random number table, with 32 rats in each group. Rats in sham injury group were sham injured on the back by immersing in 37 C warm water for 12 s. Rats in burn group and ulinastatin group were inflicted with 30% total body surface area full-thickness scald (hereinafter referred to as burn) on the back by immersing in 94 C hot water for 12 s. Immediately after injury, rats in each group were intraperitoneally injected with saline (40 mL/kg), meanwhile rats in ulinastatin group were intraperitoneally injected with ulinastatin (4*10(4) U/kg), once per 12 h, till post injury hour 72. Eight rats of each group were respectively selected on post injury day (PID) 1, 3, 5, and 7 to collect abdominal aortic blood samples. Serum content of HMGB1 was detected by enzyme linked immunosorbent assay (ELISA). And then, rats of the 3 groups were sacrificed immediately to collect spleens and separate CD4(+) CD25(+) Tregs and CD4(+) T lymphocytes. Flow cytometer was used to detect positive expression rates of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and forkhead-winged helix transcription factor p3 (Foxp3) in CD4(+) CD25(+) Tregs. Content of IL-10 in culture supernatant of CD4(+) CD25(+) Tregs, and content of interleukin 2 (IL-2), IL-4, and gamma interferon (IFN-gamma) in culture supernatant of CD4(+) T lymphocytes was detected by ELISA. The proliferative activity of CD4(+) T lymphocytes was determined by microplate reader. The sample number of above mentioned experiments was 8 at each time point in each group. Data were processed with analysis of variance of factorial design and LSD test. RESULTS: (1) Compared with that in sham injury group, serum content of HMGB1 of rats in burn group was significantly increased from PID 1 to 7 (with P values below 0.01). Compared with that in burn group, serum content of HMGB1 of rats in ulinastatin group was significantly decreased from PID 1 to 7 (with P values below 0.01). (2) Compared with those in sham injury group, the positive expression rates of CTLA-4 and Foxp3 in CD4(+) CD25(+) Tregs and content of IL-10 in culture supernatant of CD4(+) CD25(+) Tregs of rats in burn group were significantly increased from PID 1 to 7 (with P values below 0.01), peaking on PID 3 [(65+/-10)%, (76+/-10)%, and (28.2+/-4.4) pg/mL respectively]. These 3 indexes of rats in sham injury group on PID 3 were (45+/-7)%, (46+/-7)%, and (11.2+/-2.3) pg/mL respectively. Compared with those in burn group, the positive expression rates of CTLA-4 and Foxp3 in CD4(+) CD25(+) Tregs and content of IL-10 in culture supernatant of CD4(+) CD25(+) Tregs of rats in ulinastatin group were significantly decreased from PID 1 to 7 (P<0.05 or P<0.01), reaching the nadir on PID 7 [(43+/-6)%], PID 1 [(50+/ 8)%], and PID 7 [(12.4+/-3.4) pg/mL] respectively. These 3 indexes of rats in burn group on PID 7, 1, and 7 were (58+/-8)%, (71+/-9)%, and (19.7+/-2.8) pg/mL respectively. (3) Compared with those in sham injury group, the content of IL-2 and IFN-gamma in culture supernatant of CD4(+) T lymphocytes of rats was significantly decreased, while the content of IL-4 in culture supernatant of CD4(+) T lymphocytes of rats was significantly increased in burn group from PID 1 to 7, with P values below 0.01. Compared with that in burn group, the content of IL-2 and IFN-gamma in culture supernatant of CD4(+) T lymphocytes of rats was significantly increased, while the content of IL-4 in culture supernatant of CD4(+) T lymphocytes of rats was significantly decreased in ulinastatin group from PID 1 to 7, P<0.05 or P<0.01. (4) Compared with that in sham injury group, the proliferative activity of CD4(+) T lymphocytes of rats in burn group was significantly decreased from PID 1 to 7 (with P values below 0.01). Compared with that in burn group, the proliferative activity of CD4(+) T lymphocytes of rats in ulinastatin group was significantly increased from PID 1 to 7 (with P values below 0.01). CONCLUSIONS: Ulinastatin can weaken the immunosuppressive function mediated by splenic CD4(+) CD25(+) Tregs in severely burned rats, and improve proliferative function and secretory function of splenic CD4(+) T lymphocytes, which may be attributed to the inhibiting effect of ulinastatin on the release of HMGB1 in large amount. PMID- 27188488 TI - [Analysis of clinical characteristics of 187 patients with Marjolin's ulcers]. AB - OBJECTIVE: To analyze the etiology and clinical characteristics of Marjolin's ulcer, and to explore its prevention and treatment. METHODS: Medical records of 187 patients with Marjolin's ulcers admitted to the Department of Burns and Reconstructive Surgery of Xiangya Hospital of Central South University from January 1998 to May 2015 were retrospectively analyzed, including gender, age of onset of initial injury or primary disease, age of onset of Marjolin's ulcer, initial injury or primary disease, length of latency, lengths of pre- and post ulceration periods, lesion site, lesion type, lesion area, local scar tension, histopathological type, degree of carcinoma cell differentiation, bone invasion and lymphadenopathy, treatment, and prognosis. The relationships between the age of onset of initial injury or primary disease and the length of latency, and the length of pre-ulceration period and the length of post-ulceration period were assessed by Spearman correlation analysis. The recurrence rates were processed with Fisher's exact test. RESULTS: (1) Among the patients, the ratio of male to female was nearly 1.6:1.0. The age of onset of initial injury or primary disease was 0.17-78.00 (17+/-18) years, and the age of onset of Marjolin's ulcers was 18 84 (49+/-14) years. (2) The most common initial injury among the patients was flame burn. The length of latency was 0.25-74.00 (32+/-16) years, and the lengths of pre- and post-ulceration periods were 0-73.00 (26+/-19) years and 0.08-59.00 (6+/-11) years respectively. The common lesion sites were the lower limbs and head and face. The rodent ulcer was the most common lesion type, and the lesion area was 1-625 (69+/-110) cm(2). There were obviously negative correlations between the age of onset of initial injury or primary disease and the length of latency, as well as the length of pre-ulceration period and the length of post ulceration period (with r values respectively -0.71 and -0.50, P values below 0.01). The pathological scars of strong tension around lesions were seen in 176 cases. (3) The major histopathological type was squamous cell carcinoma, with high cell differentiation in most cases. (4) Bone invasion of carcinoma cells was observed in 59 cases. Lymph node enlargement was observed in 100 cases, and lymph node metastasis was observed in 18 cases. (5) Twenty patients did not receive any surgery, while 167 patients were treated by surgery with lesion extended resection as the main method. According to the condition of wound after the lesion extended resection, the wounds were mainly repaired by skin grafting and transplantation of local skin flap. The majority of wounds in 139 patients who underwent lesion extended resection were repaired in one surgery. Twenty-eight patients out of 104 followed-up cases had recurrence after surgery, mainly seen on head and face, upper limb, lower limb, and buttock, and there was no significant difference among them (P>0.05). The recurrence time of most patients was longer than 6 months after cure. CONCLUSIONS: Patients with Marjolin's ulcers in younger age of onset of initial injury or primary disease tend to have longer latency, during which the shorter the pre-ulceration period is, the longer the post-ulceration period will be. Marjolin's ulcers are prone to occur in scar sites with large tension. Early treatment of high tension scar and scar ulcer is important in prevention, and surgery is the optimal treatment for Marjolin's ulcers. Regular follow-up should be carried out owning to recurrence rate in certain degree after surgery. PMID- 27188489 TI - [Effects of estrogen on epidermis growth of mice and proliferation of human epidermal cell line HaCaT and its mechanism]. AB - OBJECTIVE: To observe the effects of estrogen on epidermis growth of mice and proliferation of keratinocytes (human epidermal cell line HaCaT), and to explore its mechanism. METHODS: (1) Five adult C57BL/6 mice in estrus cycle were identified by vaginal exfoliative cytology diagnosis and set as estrus group, while another 5 adult C57BL/6 mice with ovary resected before sexual development were set as ovariectomized group. The full-thickness skin from the tail root of mice in two groups were collected. The thickness of epidermis was observed and measured after HE staining. The distribution of proliferating cell nuclear antigen (PCNA)-positive cells in epidermis was observed by immunohistochemical staining, the number of which was counted. (2) HaCaT cells in logarithmic growth phase were cultured with RPMI 1640 nutrient solution containing 10% fetal bovine serum, and they were divided into negative control group (NC), pure estradiol group (PE), protein kinase B (Akt) inhibitor group (AI), and extracellular signal regulated kinase (ERK) inhibitor group (EI) according to the random number table, with 20 wells in each group. To nutrient solution of each group, 1 MUL dimethyl sulfoxide, 1 MUL 17beta-estradiol (100 nmol/L), 1 MUL LY294002 (10 MUmol/L), and 1 MUL PD98059 (30 MUmol/L) were added in group NC, group PE, group AI, and group EI respectively, and the last two groups were added with 1 MUL 17beta-estradiol (100 nmol/L) in addition. At post culture hour (PCH) 0 (immediately after culture), 24, 48, 72, 5 wells of cells from each group were collected to detect the proliferation activity of cells by cell counting kit 8 and microplate reader. (3) HaCaT cells in logarithmic growth phase were collected, grouped, and treated with the above-mentioned methods, with 3 wells in each group. At PCH 72, cell cycle distribution was detected by flow cytometer to calculate proliferation index (PI) of cells. (4) HaCaT cells in logarithmic growth phase were collected, grouped, and treated with the above-mentioned methods, with 3 dishes in each group. At PCH 72, the protein levels of phosphorylated Akt (p-Akt), phosphorylated ERK (p-ERK), and PCNA were determined with Western blotting. The cell experiments were repeated for 3 times. Data were processed with t test, one way analysis of variance, analysis of variance of factorial design, and LSD test. RESULTS: (1) The epidermis thickness of mice in ovariectomized group was (33.5+/ 3.0) MUm, which was obviously thinner than that in estrus group [(51.4+/-3.1) MUm, t=20.7, P<0.01]. The PCNA-positive cells mainly aggregated in the basal layer of epidermis of mice in two groups. The number of PCNA-positive cells in epidermis of mice in ovariectomized group was 37+/-12 per 200 fold visual field, obviously fewer than that in estrus group (96+/-15 per 200 fold visual field, t=15.3, P<0.01). (2) During PCH 0 to 48, there were no significant differences in the proliferation activity of cells between group PE and group NC (with P values above 0.05). At PCH 72, compared with that in group NC, the proliferation activity of cells in group PE was obviously increased (P<0.01). The proliferation activity of cells in groups AI and EI was obviously lower than that in the previous two groups (with P values below 0.01). (3) Compared with that in group NC [(51.6+/-1.1)%], the PI of cells in group PE was obviously increased [(58.5+/ 0.8)%, P<0.05]. The PI values of cells in groups AI and EI were (34.9+/-0.8)% and (48.2+/-0.4)% respectively, both obviously lower than those in the previous two groups (with P values below 0.01). (4) Compared with that of group NC (0.566+/ 0.034), the protein level of p-Akt in cells of group PE was significantly increased (1.048+/-0.077, P<0.01). Compared with that of group PE, the protein level of p-Akt was obviously decreased in cells of groups AI and EI (respectively 0.682+/-0.095 and 0.672+/-0.019, with P values below 0.01). Compared with that of group NC (0.469+/-0.013), the protein level of p-ERK obviously increased in cells of groups PE, AI, and EI (respectively 1.064+/-0.089, 1.010+/-0.038, 0.778+/ 0.065, with P values below 0.01). The protein level of p-ERK in cells of group EI was obviously lower than that in group PE (P<0.01). Compared with that of group NC (0.386+/-0.053), the protein level of PCNA was obviously increased in cells of group PE (0.743+/-0.043, P<0.01). The protein levels of PCNA in cells of groups AI and EI were 0.264+/-0.019 and 0.223+/-0.065 respectively, both obviously lower than those in the previous two groups (with P values below 0.01). CONCLUSIONS: Lack of estrogen damages the growth ability of epidermis of mice. Estrogen (17beta-estradiol) can promote the proliferation of HaCaT cells by increasing the expression of PCNA via activating ERK/Akt signaling pathway. PMID- 27188490 TI - [Effects of transfection of human epidermal growth factor gene with adenovirus vector on biological characteristics of human epidermal cells]. AB - OBJECTIVE: To investigate the suitable transfection condition of human epidermal cells (hECs) with human epidermal growth factor (EGF) gene by adenovirus vector (Ad-hEGF) and its effects on the biological characteristics of hECs. METHODS: hECs were isolated from deprecated human fresh prepuce tissue of circumcision by enzyme digestion method and then sub-cultured. hECs of the third passage were used in the following experiments. (1) Cells were divided into non-transfection group and 5, 20, 50, 100, 150, and 200 fold transfection groups according to the random number table (the same grouping method below), with 3 wells in each group. Cells in non-transfection group were not transfected with Ad-hEGF gene, while cells in the latter six groups were transfected with Ad-hEGF gene in multiplicities of infection (MOI) of 5, 20, 50, 100, 150, and 200 respectively. The morphology of the cells was observed with inverted phase contrast microscope, and expression of green fluorescent protein of the cells was observed with inverted fluorescence microscope at transfection hour (TH) 24, 48, and 72. (2) Another three batches of cells were collected, grouped, and treated as above, respectively. Then the transfection rate of Ad-hEGF gene was detected by flow cytometer (n=3), the mass concentration of EGF in culture supernatant of cells was detected by enzyme-linked immunosorbent assay (n=6), and the proliferation activity of cells was detected by cell counting kit 8 (CCK8) and microplate reader (n=6) at TH 24, 48, and 72, respectively. (3) Cells were collected and divided into non-transfection group and transfection group, with 6 wells in each group. Cells in non-transfection group were cultured with culture supernatant of cells without transfection, while cells in transfection group were cultured with culture supernatant of cells which were transfected with Ad-hEGF gene in the optimum MOI (50). CCK8 and microplate reader were used to measure the biological activity of EGF secreted by cells on culture day 1, 3, and 5. (4) Cells were collected and divided into non-transfection group and transfection group, with 12 wells in each group. Cells in non-transfection group were not transfected with Ad hEGF gene, while cells in transfection group were transfected with Ad-hEGF gene in the optimum MOI (50). The expression levels of cytokeratin 14 (CK14) and CK19 of cells were measured by immunofluorescence staining at TH 24. (5) Cells were collected, grouped, and treated as in (4), with 6 wells in each group. At post scratch hour (PSH) 0 (immediately after scratch), 12, 24, and 48, the migration distance of cells was observed and measured with inverted phase contrast microscope. Data were processed with analysis of variance of factorial design, analysis of variance for repeated measurement, and LSD test. RESULTS: (1) At TH 24 and 48, morphology of cells in each transfection group and non-transfection group were similar. Compared with that in non-transfection group, the cell debris increased significantly in 200 fold transfection group at TH 72. At TH 24, 48, and 72, the expression of green fluorescent protein was not seen in cells of non transfection group, whereas it increased in cells of transfection group over transfection time. (2) The transfection rate of Ad-hEGF gene of cells in each transfection group increased gradually over transfection time. At TH 72, the transfection rates of Ad-hEGF gene of cells in 50-200 fold transfection groups were all above 90%, while the transfection rates of Ad-hEGF gene of cells in non transfection group, 5, and 20 fold transfection groups were (0.51+/-0.20)%, (62.44+/-6.23)%, and (75.00+/-5.43)% respectively, which were obviously lower than the rate in 50 fold transfection group [(93.12+/-2.55)%, with P values below 0.01]. The mass concentration of EGF in culture supernatant of cells in each transfection group increased gradually over transfection time. At TH 72, the mass concentration of EGF in culture supernatant of cells in 50 fold transfection group was obviously higher than that in each of the other groups (with P values below 0.01). The proliferation activity of cells in each group at TH 24 and 48 was similar (with P values above 0.05). At TH 72, the proliferation activity of cells in 200 fold transfection group was obviously lower than that in other groups (with P values below 0.05). (3) On culture day 1, the biological activity of EGF secreted by cells in two groups was similar (P>0.05). On culture day 3 and 5, the biological activity of EGF secreted by cells in transfection group were obviously higher than that in non-transfection group (with P values below 0.01). (4) At TH 24, the expression levels of CK14 and CK19 of cells in transfection group were higher than those in non-transfection group. (5) The width of scratch in two groups was nearly the same at PSH 0. At PSH 12-48, the migration distance of cells in transfection group was obviously longer than that in non-transfection group (with P values below 0.01). CONCLUSIONS: The suitable range of MOI of hECs transfected with Ad-hEGF gene is 50-150, and 50 is the optimum. hECs transfected with Ad-hEGF gene with MOI 50 can effectively express the EGF gene and keep its good abilities of proliferation, differentiation, and migration, as well. PMID- 27188491 TI - [Advances in the research of natural polymeric materials and their derivatives in the manufacture of scaffolds for dermal tissue engineering]. AB - Natural polymeric materials and their derivatives are organic macromolecular compounds which exist in plants, animals, and micro-organisms. They have been widely used in the preparation of scaffolds for skin tissue engineering recently because of their good histocompatibility and degradability, and low immunogenicity. With the improvement of the preparation technics, composite materials are more commonly used to make scaffolds for dermal tissue engineering. This article summarizes the classification and research status of the commonly used natural polymer materials, their derivatives, and composite scaffold materials, as well as makes a prospect of the research trends of dermal scaffold in the future. PMID- 27188492 TI - The contribution of inflammasome components on macrophage response to surface nanotopography and chemistry. AB - Implantable devices have become an established part of medical practice. However, often a negative inflammatory host response can impede the integration and functionality of the device. In this paper, we interrogate the role of surface nanotopography and chemistry on the potential molecular role of the inflammasome in controlling macrophage responses. To achieve this goal we engineered model substrata having precisely controlled nanotopography of predetermined height and tailored outermost surface chemistry. Bone marrow derived macrophages (BMDM) were harvested from genetically engineered mice deficient in the inflammasome components ASC, NLRP3 and AIM2. These cells were then cultured on these nanoengineered substrata and assessed for their capacity to attach and express pro-inflammatory cytokines. Our data provide evidence that the inflammasome components ASC, NLRP3 and AIM2 play a role in regulating macrophage adhesion and activation in response to surface nanotopography and chemistry. The findings of this paper are important for understanding the inflammatory consequences caused by biomaterials and pave the way to the rational design of future implantable devices having controlled and predictable inflammatory outcomes. PMID- 27188493 TI - Specific immunotherapy for rhinitis and asthma with a subcutaneous hypoallergenic high-dose house dust mite extract: results of a 9-month therapy. AB - AIM: Effectiveness of a 9-month specific immunotherapy with a subcutaneous hypoallergenic high-dose house dust mite extract to reduce allergic symptoms as perceived by patients and physicians was assessed. PATIENTS & METHODS: An observational, retrospective, multicenter study was carried out in patients diagnosed with asthma and/or rhinitis caused by house dust mites having started specific immunotherapy with Acaroid((r)). Primary end point was perceived effectiveness. RESULTS: A total of 409 patients were included. According to physician-completed visual analogue scale, a 58.1% clinical improvement was observed. Patient-completed visual analogue scale showed a 69.8% clinical improvement. The need for unscheduled/emergency healthcare, as an indication of poor quality of life, showed a significant reduction. CONCLUSION: Our results confirm in a real-world setting the findings from randomized clinical trials of high-dose house dust mites allergoid immunotherapy with a subcutaneous hypoallergenic high-dose house dust mite extract. PMID- 27188494 TI - Analysis of Lyrics from Group Songwriting with Bereaved Children and Adolescents. AB - BACKGROUND: Songwriting is a group intervention that is often used to help bereaved children and adolescents express thoughts and feelings associated with grief experiences. Few studies have examined the lyrical content of songs written by bereaved children/adolescents and how thematic content may vary by age and developmental understanding of death. OBJECTIVE: The purpose of this study was to determine whether experiences of songwriting and lyrical content of songs written by children and adolescents participating in a bereavement camp vary by age. METHODS: Thirty-three participants, ages 6-16, were grouped according to age (child, tween, or teen) and asked to write a group song. Analysis of song lyrics was based on both inductive and deductive content analysis processes. A seven item questionnaire was also used with the tween and teen groups to gather descriptive information about the songwriting process, including participant views on benefits, enjoyment, and preferences. RESULTS: Analyses revealed a total of five different themes among the three age groups, with two of the five themes present across the age groups. A majority of the participants enjoyed the songwriting process, but no clear indication of preference for verbal or written contribution was determined based on age or gender. CONCLUSIONS: The lyric content of the songs varied across the age groups, with the older groups providing more diverse content and demonstrating growth in their understanding of death. Providing participants both written and verbal options to contribute to the songwriting process allows for individual preferences among tweens and teens. PMID- 27188497 TI - The importance of intraspecific variation in tree responses to elevated [CO2]: breeding and management of future forests. PMID- 27188496 TI - A small synthetic molecule functions as a chloride-bicarbonate dual-transporter and induces chloride secretion in cells. AB - A C2 symmetric small molecule composed of l-phenylalanine and isophthalamide was found to function as a Cl(-)/HCO3(-) dual transporter and self-assemble into chloride channels. In Ussing-chamber based short-circuit current measurements, this molecule elicited chloride-dependent short-circuit current (Isc) increase in both Calu-3 cell and CFBE41o-cell (with F508del mutant CFTR) monolayers. PMID- 27188495 TI - Post-Traumatic Stress Symptoms and Burnout Among Medical Rescue Workers 4 Years After the Great East Japan Earthquake: A Longitudinal Study. AB - OBJECTIVE: This study aimed to evaluate factors associated with post-traumatic stress disorder (PTSD) symptoms and burnout 4 years after the Great East Japan Earthquake among medical rescue workers in Disaster Medical Assistance Teams (DMATs). METHODS: We examined participants' background characteristics, prior health condition, rescue work experiences, and the Peritraumatic Distress Inventory (PDI) score at 1 month after the earthquake. Current psychological condition was assessed by the Impact of Event Scale-Revised and Maslach Burnout Inventory administered 4 years after the earthquake. By applying univariate and multivariate linear regression analyses, we assessed the relative value of the PDI and other baseline variables for PTSD symptoms and burnout at 4 years after the earthquake. RESULTS: We obtained baseline data from 254 participants during April 2 to 22, 2011. Of the 254 participants, 188 (74.0%) completed the follow-up assessment. PDI score 1 month after the earthquake was associated with symptoms of PTSD (beta=0.35, P<.01) and burnout (beta=0.21, P<.01). Stress before deployment was a related factor for burnout 4 years after the earthquake in these medical rescue workers (beta=2.61, P<.04). CONCLUSIONS: It seems important for DMAT headquarters to establish a routine system for assessing the PDI of medical rescue workers after deployment and screen those workers who have high stress prior to deployment (Disaster Med Public Health Preparedness. 2016;10:848-853). PMID- 27188498 TI - Development and validation of the Japanese version of cognitive flexibility scale. AB - BACKGROUND: Various instruments have been developed to assess cognitive flexibility, which is an important construct in psychology. Among these, the self report cognitive flexibility scale (CFS) is particularly popular for use with English speakers; however, there is not yet a Japanese version of this scale. This study reports on the development of a Japanese version of the cognitive flexibility scale (CFS-J), and the assessment of its internal consistency, test retest reliability, and validities. METHODS: We used the standard translation back-translation process to develop the Japanese wording of the items and tested these using a sample of 335 eligible participants who did not have a mental illness, were aged 18 years or older, and lived in the suburbs of Tokyo. Participants included office workers, public servants, and college students; 71.6 % were women and 64.8 % were students. The translated scale's internal consistency reliability was assessed by calculating Cronbach's alpha and McDonald's omega, and test-retest reliability was assessed with 107 eligible participants via intra-class correlation coefficient (ICC) and Spearman's correlation of coefficient. Exploratory factory analysis (EFA) and correlations with other scales were used to examine the factor-based and concurrent validities of the CFS-J. RESULTS: Results indicated that the CFS-J has good internal consistency (Cronbach's alpha = 0.847, McDonald's omega = 0.871) and acceptable test-retest reliability (Spearman's = 0.687, ICC = 0.689). EFA provided evidence that the CFS-J has a one-factor structure and factor loadings were generally appropriate. The total CFS-J score was significantly and positively correlated with the cognitive flexibility inventory-Japanese version and its two subscales, along with the cognitive control scale and the positive subscale of the short Japanese version of the automatic thought questionnaire-revised (ATQ-R); further, it had a significantly negative correlation with the negative subscale of the ATQ R (ps < 0.001). This study developed a Japanese version of the cognitive flexibility scale and confirmed its reliability and validity among a sample of people with no current mental illness, who were living in the suburbs of Tokyo. PMID- 27188500 TI - An exploratory study into the application of psychological theories and therapies in Australian mental health occupational therapy practice: Challenges to occupation-based practice. AB - BACKGROUND: While legitimate practice tools have been the subject of debate within the profession, little attention has been paid to psychological frames of reference (PFsOR). Hence, this article explores the ways psychological theories and therapies shape occupation-based practice in mental health settings. METHODOLOGY: Narrative inquiry methods and thematic analysis were used to explore the career stories of nine occupational therapists who had worked in mental health practice for more than five years. FINDINGS: Respondents found it difficult to hold onto their occupational focus in the psychology-dominated world of mental health practice. The main themes to emerge were (i) tension between occupation and psychology; (ii) overwhelming pressures to adopt PFsOR; (iii) resistance to PFsOR; and (iv) using PFsOR to enhance professional repertoires. Findings pointed to the need to ensure PFsOR include occupational considerations for occupation-based practice in mental health. CONCLUSION: A occupation-based perspective means balancing PFsOR with occupation-based considerations, so service-user issues are holistically addressed. There is a need to critically review occupational therapists' use of PFsOR lest their most visible practical actions appear psychologically based rather than occupation based. PMID- 27188499 TI - [Implementation of a thermal management concept to prevent perioperative hypothermia : Results of a 6-month period in clinical practice]. AB - BACKGROUND: Perioperative hypothermia is defined as a core temperature below 36 degrees C. The literature shows that perioperative hypothermia is a frequent but potentially preventable complication of the surgical process. The risk of experiencing perioperative hypothermia is inherent for all anesthetized patients, independent of the type of surgery. Unless preventative measures are taken, perioperative hypothermia occurs in 50 to 70 % of all surgical patients. In Germany and Austria the guideline "Preventing inadvertent perioperative hypothermia" has been published. In Wolfsburg we started already in 2012 with a standard operating procedure to prevent perioperative hypothermia in all surgical patients. In two clinical departments we established an additional prewarming protocol starting prior to induction of anaesthesia on the normal ward on the day of surgery. MATERIAL AND METHODS: For a period of 6 months we analyzed all temperature data of patients having undergone surgery, beginning before the start of general anaesthesia until the end of the operation. RESULTS: In total 3228 patients were enrolled into the study. Prewarming was performed in 1329 patients. In 1902 patients active warming was limited to the intraoperative period. The total rate of hypothermia in all patients was 32.6 %, whereas the rate of hypothermia at the end of the operation was 19.3 %. In the group of patients without prewarming the overall rate was 39.1 vs. 25 % at the end of the operation. In the groups of patients with prewarming the total rates of hypothermia were 25.2 and 24.7 % overall and 14.4 and 12.5 % at the end of the operation. In multifactorial regression it could be shown that patients without prewarming had a 1.8-fold increased risk of perioperative hypothermia compared to patients with intraoperative warming only. CONCLUSION: We conclude that temperature management is a challenge in the clinical situation, and that it is difficult to achieve rates of hypothermia close to zero. The addition of prewarming was very effective in improving the results in our patients. PMID- 27188502 TI - Nickel-Catalyzed Hiyama-type Decarboxylative Coupling of Propiolic Acids and Organosilanes. AB - A Ni catalytic system was developed for the decarboxylative coupling reaction of alkynyl carboxylic acids with organosilanes. Ni(acac)2 and 1,10-phenanthroline showed the best result in the presence of CsF and CuF2 at 120 degrees C. This system tolerated the presence of alkyl, alkoxy, halogen, nitro, cyano, ketone, and ester functional groups. Moreover, the reaction with but-2-ynedioic acid and organosilane afforded the corresponding symmetrical diarylalkynes. PMID- 27188501 TI - CXCR2 Inhibition in Human Pluripotent Stem Cells Induces Predominant Differentiation to Mesoderm and Endoderm Through Repression of mTOR, beta Catenin, and hTERT Activities. AB - On the basis of our previous report verifying that chemokine (C-X-C motif) receptor 2 (CXCR2) ligands in human placenta-derived cell conditioned medium (hPCCM) support human pluripotent stem cell (hPSC) propagation without exogenous basic fibroblast growth factor (bFGF), this study was designed to identify the effect of CXCR2 manipulation on the fate of hPSCs and the underlying mechanism, which had not been previously determined. We observed that CXCR2 inhibition in hPSCs induces predominant differentiation to mesoderm and endoderm with concomitant loss of hPSC characteristics and accompanying decreased expression of mammalian target of rapamycin (mTOR), beta-catenin, and human telomerase reverse transcriptase (hTERT). These phenomena are recapitulated in hPSCs propagated in conventional culture conditions, including bFGF as well as those in hPCCM without exogenous bFGF, suggesting that the action of CXCR2 on hPSCs might not be associated with a bFGF-related mechanism. In addition, the specific CXCR2 ligand growth-related oncogene alpha (GROalpha) markedly increased the expression of ectodermal markers in differentiation-committed embryoid bodies derived from hPSCs. This finding suggests that CXCR2 inhibition in hPSCs prohibits the propagation of hPSCs and leads to predominant differentiation to mesoderm and endoderm owing to the blockage of ectodermal differentiation. Taken together, our results indicate that CXCR2 preferentially supports the maintenance of hPSC characteristics as well as facilitates ectodermal differentiation after the commitment to differentiation, and the mechanism might be associated with mTOR, beta-catenin, and hTERT activities. PMID- 27188503 TI - Elevated blood pressure is not associated with accelerated glomerular filtration rate decline in the general non-diabetic middle-aged population. AB - Although hypertension is a risk factor for end-stage renal disease, this complication develops in only a minority of hypertensive patients. Whether non malignant hypertension itself is sufficient to cause reduced glomerular filtration rate (GFR) is unclear. Therefore, we investigated whether elevated blood pressure (BP) was associated with accelerated GFR decline in the general population. The study was based on the Renal Iohexol Clearance Survey in Tromso 6 (RENIS-T6), which included a representative sample of 1594 individuals aged 50 to 62 years from the general population without baseline diabetes or kidney or cardiovascular disease. GFR was measured as iohexol clearance at baseline and follow-up after a median observation time of 5.6 years. BP was measured according to a standardized procedure. The mean (SD) GFR decline rate was 0.95 (2.23) ml/min/yr. In multivariable adjusted linear mixed regressions with either baseline systolic or diastolic BP as the independent variable, there were no statistically significant associations with GFR decline. Thus, elevated BP is not associated with accelerated mean GFR decline in the general middle-aged population. Hence, additional genetic and environmental factors are probably necessary for elevated BP to develop manifest chronic kidney disease in some individuals. PMID- 27188504 TI - Defective postreperfusion metabolic recovery directly associates with incident delayed graft function. AB - Delayed graft function (DGF) following kidney transplantation affects long-term graft function and survival and is considered a manifestation of ischemia reperfusion injury. Preclinical studies characterize metabolic defects resulting from mitochondrial damage as primary driver of ischemia reperfusion injury. In a comprehensive approach that included sequential establishment of postreperfusion arteriovenous concentration differences over the human graft, metabolomic and genomic analysis in tissue biopsies taken before and after reperfusion, we tested whether the preclinical observations translate to the context of clinical DGF. This report is based on sequential studies of 66 eligible patients of which 22 experienced DGF. Grafts with no DGF immediately recovered aerobic respiration as indicated by prompt cessation of lactate release following reperfusion. In contrast, grafts with DGF failed to recover aerobic respiration and showed persistent adenosine triphosphate catabolism indicated by a significant persistently low post reperfusion tissue glucose-lactate ratio and continued significant post-reperfusion lactate and hypoxanthine release (net arteriovenous difference for lactate and hypoxanthine at 30 minutes). The metabolic data for the group with DGF point to a persistent post reperfusion mitochondrial defect, confirmed by functional (respirometry) and morphological analyses. The archetypical mitochondrial stabilizing peptide SS-31 significantly preserved mitochondrial function in human kidney biopsies following simulated ischemia reperfusion. Thus, development of DGF is preceded by a profound post-reperfusion metabolic deficit resulting from severe mitochondrial damage. Strategies aimed at preventing DGF should be focused on safeguarding a minimally required post reperfusion metabolic competence. PMID- 27188506 TI - Change of government's subsidization policy improves smoking cessation services: a cross-sectional study from the perspectives of physicians. AB - BACKGROUND: The Taiwanese government increased financial subsidies for smoking cessation services in 2012. We aimed to evaluate the effects of this new policy on smoking cessation services from the physician's perspective. METHODS: This was a cross-sectional nationwide survey. Physicians who provided smoking cessation services for more than ten patient encounters in the preceding year of the new policy (February 2011 to March 2012) were recruited. The questionnaire was developed by two experts and was validated by a committee consisting of 11 delegates. RESULTS: We sent a total of 1,319 questionnaires. The response rate was 45.9 %. The majority of respondents were male (88.4 %), middle-aged (65.3 %), and worked as family physicians (56.1 %). Most physicians agreed that the new policy had increased the number of patients seeking smoking cessation, increased patients' willingness to adopt pharmacotherapy, helped physicians to prescribe medications, improved patients' adherence to medications, and improved quality of care. These changes were most prominent in medical centers. Changes in the practice of the 5As (ask, advise, assess, assist, arrange) were moderate. Among different medical settings, the most significant change was an increase in the expenditure on smoking cessation medications. CONCLUSIONS: The new subsidization policy in Taiwan has improved smoking cessation services. Overall, physicians reported positive effects of the new policy. Further study is warranted to evaluate the long-term influence of the policy. PMID- 27188505 TI - Non-HLA antibodies against endothelial targets bridging allo- and autoimmunity. AB - Detrimental actions of donor-specific antibodies (DSAs) directed against both major histocompatibility antigens (human leukocyte antigen [HLA]) and specific non-HLA antigens expressed on the allograft endothelium are a flourishing research area in kidney transplantation. Newly developed solid-phase assays enabling detection of functional non-HLA antibodies targeting G protein-coupled receptors such as angiotensin type I receptor and endothelin type A receptor were instrumental in providing long-awaited confirmation of their broad clinical relevance. Numerous recent clinical studies implicate angiotensin type I receptor and endothelin type A receptor antibodies as prognostic biomarkers for earlier occurrence and severity of acute and chronic immunologic complications in solid organ transplantation, stem cell transplantation, and systemic autoimmune vascular disease. Angiotensin type 1 receptor and endothelin type A receptor antibodies exert their pathophysiologic effects alone and in synergy with HLA DSA. Recently identified antiperlecan antibodies are also implicated in accelerated allograft vascular pathology. In parallel, protein array technology platforms enabled recognition of new endothelial surface antigens implicated in endothelial cell activation. Upon target antigen recognition, non-HLA antibodies act as powerful inducers of phenotypic perturbations in endothelial cells via activation of distinct intracellular cell-signaling cascades. Comprehensive diagnostic assessment strategies focusing on both HLA-DSA and non-HLA antibody responses could substantially improve immunologic risk stratification before transplantation, help to better define subphenotypes of antibody-mediated rejection, and lead to timely initiation of targeted therapies. Better understanding of similarities and dissimilarities in HLA-DSA and distinct non-HLA antibody-related mechanisms of endothelial damage should facilitate discovery of common downstream signaling targets and pave the way for the development of endothelium-centered therapeutic strategies to accompany intensified immunosuppression and/or mechanical removal of antibodies. PMID- 27188508 TI - Immunological response to quadrivalent HPV vaccine in treatment of recurrent respiratory papillomatosis. AB - Aim of this study was to explore influence of the quadrivalent HPV vaccine (Gardasil((r))) on the immune status of recurrent respiratory papillomatosis (RRP) patients. In retrospective observational study, six RRP patients who received the quadrivalent HPV vaccine and whose HPV seroreactivity was measured were included. Multiplex HPV Serology was used to determine HPV-specific antibodies pre- and post-vaccination. Surgical interventions and patient records were analyzed. Five HPV6 and 1 HPV11 infected patient were included. Mean antibody reactivity against the associated HPV type rose from 1125 median fluorescence intensity (MFI) pre-vaccination to 4690 MFI post-vaccination (p < 0.001). Median post-vaccination follow-up was 4 years. Poisson regression analysis showed that the quadrivalent HPV vaccine decreased the incidence rate of surgeries. The immune system of RRP patients is able to increase antibody reactivity against the associated HPV type. A double blind randomized controlled trial is needed to determine whether this immunological increase can cause decrease in number of surgeries. PMID- 27188507 TI - Management of recurrent head and neck cancer: variables related to salvage surgery. AB - After a local and/or regional recurrence of head and neck squamous cell carcinoma (HNSCC) not all patients are candidates to salvage treatment. The objective of this study was to identify the variables related to performance of salvage surgery with curative intent in these patients. We performed a retrospective study of 1088 HNSCC patients with a local and/or regional recurrence. According to a multivariate analysis, the variables related to performance of salvage surgery were the Karnofsky index, the location and extension of the primary tumor, the initial treatment, the disease-free interval between treatment of the initial tumor and diagnosis of the recurrence, and the year the recurrence was diagnosed. Considering salvage surgery as the dependent variable, the results of a recursive partitioning analysis defined four categories of patients in function of the category of local and regional extension of the initial tumor, the location of the primary tumor, the initial treatment and the disease-free interval between treatment of the initial tumor and diagnosis of the recurrence. PMID- 27188509 TI - The effect of preoperative neutrophil, platelet and lymphocyte counts on local recurrence and survival in early-stage tongue cancer. AB - The aim of this study was to investigate the predictive value of preoperative neutrophil, platelet and lymphocyte counts in local recurrence and survival in the patients operated for early-stage squamous cell carcinoma (SCC) of the tongue. 57 patients who underwent surgery for early-stage (stage 1-2) SCC of the tongue were enrolled in the study. Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and neutrophil * PLR value (N * PLR) were used as outcome measures. Local recurrence was detected in 11 (19.3 %) patients during follow-up period. Mortality was seen in 7 (12.3 %) patients. 37 (64.9 %) patients had stage 1 and 20 (35.1 %) patients had stage 2 tumor. NLR, PLR and N * PLR cutoff values were determined as 2.26, 146,855 and 689,912, respectively, by receiver operating characteristic analysis. The relationship between NLR, PLR, N * PLR and local recurrence was statistically significant according to these cutoff values (p values 0.021, 0.020, 0.017, respectively). We suggest that NLR, PLR and N * PLR may be used to predict local recurrence, while their use in overall and disease-free survival is limited. Further studies involving large patient groups are required. PMID- 27188510 TI - Effects of resistant and susceptible rubber germplasms on development, reproduction and protective enzyme activities of Eotetranychus sexmaculatus (Acari: Tetranychidae). AB - Systematic research or technical support regarding rubber germplasm resistance against mites was not performed yet. To develop a preliminary understanding of the mite-resistance mechanisms of rubber germplasms, stably resistant rubber germplasms were obtained, the development and reproduction of Eotetranychus sexmaculatus that fed on leaves of resistant and susceptible rubber germplasms were examined in the laboratory, and the activities of protective enzymes in this mite species were also compared. The results indicated that: (1) among the 23 rubber core germplasms identified, five (IRCI12, Reyan87-6-5, IAN717, RRIM600 and RRIC52) steadily developed resistance to E. sexmaculatus; (2) E. sexmaculatus that fed on the highly resistant germplasm IRCI12 did not complete development and reproduction-the female adults laid only 4.90 eggs on average, and none of these eggs hatched; (3) the resistant germplasms extended the duration of each developmental stage, reduced the fecundity, egg hatchability, and female offspring percentage, and significantly decreased the offspring survival rate compared with the susceptible germplasms; and (4) during each developmental stage of the mites that fed on resistant rubber germplasms, decreased activities (by 0.25-fold to 0.63-fold times) of the protective enzymes peroxidase, ascorbate peroxidase, polyphenol oxidase, superoxide dismutase and catalase were observed compared with those in the mites that fed on susceptible rubber germplasms (P < 0.05). These findings may explain why E. sexmaculatus did not complete their development and reproduction on the resistant rubber germplasms. This study lays a foundation for elucidation of the mechanism of rubber resistance to mites and provides experimental material and technical support for the breeding of mite resistant rubber plants. PMID- 27188511 TI - After-pulsing, cross-talk, dark-count, and gain of MPPC under 7-T static magnetic field. AB - Multi-pixel photon counters (MPPCs) have been used instead of photomultiplier tubes for positron emission tomography combined with magnetic resonance (PET-MR). However, the effects of the magnetic field (MF) on the intrinsic properties-gain, cross-talk, after-pulsing, and dark-count-have not been sufficiently investigated. Therefore, we measured these properties for two types of MPPCs S10931-50P and S12572-50P-in a static 7-T MF. These properties were measured with a pulse-shape analysis using pulse data acquired by a digital oscilloscope in the presence of the MF (w/MF) and the absence of the MF (w/o MF) by changing the supplied over-voltages (from 0.95 to 2.1 V for S10931 and from 2.1 to 3.3 V for S12572). No significant differences between the w/MF and w/o MF cases were observed for either MPPC, suggesting that the gain, cross-talk, after-pulsing, and dark-count are insensitive to a 7-T MF. The present work shows that constant MPPC performance is expected under a strong MF and demonstrates positive results for PET-MR. PMID- 27188512 TI - From Biocompatibility to Immune Engineering. PMID- 27188516 TI - The use of engineered protein materials in electrochemical devices. AB - Bioelectrochemical technologies have an important and growing role in healthcare, with applications in sensing and diagnostics, as well as the potential to be used as implantable power sources and be integrated with automated drug delivery systems. Challenges associated with enzyme-based electrodes include low current density and short functional lifetimes. Protein engineering is emerging as a powerful tool to overcome these issues. By taking advantage of the ability to precisely define protein sequences, electrodes can be organized into high performing structures, and enable the next generation of medical devices. PMID- 27188513 TI - Immunoisolation to prevent tissue graft rejection: Current knowledge and future use. AB - This review focuses on the concept of immunoisolation and how this method has evolved over the last few decades. The concept of immunoisolation came out of the need to protect allogeneic transplant tissue from the host immune system and avoid systemic side effects of immunosuppression. The latter remains a significant hurdle in clinical translation of using tissue transplants for restoring endocrine function in diabetes, growth hormone deficiency, and other conditions. Herein, we review the most significant works studying the use of hydrogels, specifically alginate and poly (ethylene glycol), and membranes for immunoisolation and discuss how this approach can be applied in reproductive biology. PMID- 27188515 TI - Enzyme-responsive polymer hydrogels for therapeutic delivery. AB - Enzymes play a central role in a spectrum of fundamental physiological processes and their altered expression level has been associated with many diseases and pathological disorders. Enzymes therefore can be exploited as a pristine biological trigger to tune material responses and to achieve controlled release of biomolecules at desired sites. This mini-review highlights enzyme-responsive polymer hydrogels for therapeutic delivery applications developed within the last five years, focusing on protease- and glycosidase-based catalyzed reactions. Strategies employed to produce responsive materials are described. Successful applications for controlled drug delivery are highlighted, and finally, future opportunities and challenges are presented. PMID- 27188518 TI - Corrigendum. AB - Irena Kasacka, Zaneta Piotrowska and Izabela Janiuk. Influence of renovascular hypertension on the distribution of vasoactive intestinal peptide in the stomach and heart of rats. Experimental Biology and Medicine 2015; 240: :1402-1407 (Original DOI: 10.1177/1535370215587533). PMID- 27188514 TI - In vitro selection technologies to enhance biomaterial functionality. AB - Cells make decisions and fate choices based in part on cues they receive from their external environment. Factors that affect the interpretation of these cues include the soluble proteins that are present at any given time, the cell surface receptors that are available to bind these proteins, and the relative affinities of the soluble proteins for their cognate receptors. Researchers have identified many of the biological motifs responsible for the high-affinity interactions between proteins and their receptors, and subsequently incorporated these motifs into biomaterials to elicit control over cell behavior. Common modes of control include localized sequestration of proteins to improve bioavailability and direct inhibition or activation of a receptor by an immobilized peptide or protein. However, naturally occurring biological motifs often possess promiscuous affinity for multiple proteins and receptors or lack programmable actuation in response to dynamic stimuli, thereby limiting the amount of control they can exert over cellular decisions. These natural motifs only represent a small fraction of the biological diversity that can be assayed by in vitro selection strategies, and the discovery of "artificial" motifs with varying affinity, specificity, and functionality could greatly expand the repertoire of engineered biomaterial properties. This minireview provides a brief summary of classical and emerging techniques in peptide phage display and nucleic acid aptamer selections and discusses prospective applications in the areas of cell adhesion, angiogenesis, neural regeneration, and immune modulation. PMID- 27188519 TI - Pathophysiology of Renal Tubular Acidosis: Core Curriculum 2016. PMID- 27188517 TI - Nanoallergens: A multivalent platform for studying and evaluating potency of allergen epitopes in cellular degranulation. AB - Degranulation caused by type I hypersensitivity (allergies) is a complex biophysical process, and available experimental models for studying relevant immunoglobulin E binding epitopes on allergen proteins lack the ability to adequately evaluate, rank, and associate these epitopes individually and with each other. In this study, we propose a new allergy model system for studying potential allergen epitopes using nanoallergens, liposomes modified to effectively display IgE binding epitopes/haptens. By utilizing the covalently conjugated lipid tails on two hapten molecules (dinitrophenol and dansyl), hapten molecules were successfully incorporated into liposomes with high precision to form nanoallergens. Nanoallergens, with precisely controlled high-particle valency, can trigger degranulation with much greater sensitivity than commonly used bovine serum albumin conjugates. In rat basophil leukemia cell experiments, nanoallergens with only 2% hapten loading were able to trigger degranulation in vitro at concentrations as low as 10 pM. Additionally, unlike bovine serum albumin-hapten conjugates, nanoallergens allow exact control over particle size and valency. By varying the nanoallergen parameters such as size, valency, monovalent affinity of hapten, and specific IgE ratios, we exposed the importance of these variables on degranulation intensity while demonstrating nanoallergens' potential for evaluating both high- and low-affinity epitopes. The data presented in this article establish nanoallergen platform as a reliable and versatile allergy model to study and evaluate allergen epitopes in mast cell degranulation. PMID- 27188520 TI - Influence of the Guest on Aggregation of the Host by Exciton-Polaron Interactions and Its Effects on the Stability of Phosphorescent Organic Light-Emitting Devices. AB - The root causes of the differences in electroluminescence stability among phosphorescent organic light-emitting devices (PHOLEDs) utilizing different emitter guests are studied. The results show that the host material plays a more influential role in limiting device stability in comparison to the guest. During the operation of a PHOLED, the host undergoes aggregation as a result of interactions between the excitons and positive polarons. The rate of this aggregation is found to be the limiting factor for device lifetime and is influenced by the choice of the guest material and its concentration. Finally, it is shown that phase segregation between the host and the guest is an important aspect of the aggregation process. As a result of this segregation, energy transfer from the host to the guest becomes increasingly less efficient, resulting in the observed gradual loss in electroluminescence efficiency in the devices over time. The findings explain why PHOLEDs utilizing different guest materials but otherwise identical material systems can have significantly different lifetimes and provide an answer to a long-lasting question in the field. PMID- 27188523 TI - First-principles study of thermal properties of borophene. AB - Very recently, a new single-element two-dimensional (2D) material borophene was successfully grown on a silver surface under pristine ultrahigh vacuum conditions which attracts tremendous interest. In this paper, the lattice thermal conductivity, phonon lifetimes, thermal expansion and temperature dependent elastic moduli of borophene are systematically studied by using first-principles. Our simulations show that borophene possesses unique thermal properties. Strong phonon-phonon scattering is found in borophene, which results in its unexpectedly low lattice thermal conductivity. Thermal expansion coefficients along both the armchair and zigzag directions of borophene show impressive negative values. More strikingly, the elastic moduli are sizably strengthened as temperature increases, and the negative in-plane Poisson's ratios are found along both the armchair and zigzag directions at around 120 K. The mechanisms of these unique thermal properties are also discussed in this paper. PMID- 27188522 TI - Inhibition of Propionibacterium acnes associated biofilm formation by Decanediol. PMID- 27188521 TI - Real-World Implementation of a Standardized Handover Program (I-PASS) on a Pediatric Clinical Teaching Unit. AB - OBJECTIVE: A standardized handover curriculum (I-PASS) has been shown to reduce preventable adverse events in a large multicenter study. We aimed to study the real-world impact of the implementation of this curriculum on handover quality, duration, and identification of unstable patients. METHODS: A prospective intervention study was conducted. We implemented the I-PASS curriculum via faculty education and resident workshops. Resident handover on the clinical teaching unit was videorecorded, and written handover documents were collected for 2 weeks before and after the intervention. We examined the inclusion of key elements on handover documents before and after intervention using logistic regression models accounting for multiple handovers per patient. Duration of handover was compared using a linear regression model adjusting for number of patients. Qualitative content analysis was used to describe observable differences in verbal handover recordings and written critical care consultations. RESULTS: A total of 1275 handovers were included, comprising 364 inpatients. There was a significant increase (P < .05) in 7 of 11 key elements and a significant decrease in written physical examination findings after the intervention. No significant change was found in handover duration. Qualitative video analysis revealed observable differences in handover collaboration and organization. After the intervention, patients with critical care needs overnight were correctly identified as requiring close monitoring during handover. CONCLUSIONS: Handover training resulted in consistent inclusion of key elements and was characterized by collaboration between participants and improved organization without significant increase in handover duration. Appropriate identification and response to clinically deteriorating patients was also found using the I-PASS model. PMID- 27188524 TI - Genetic polymorphisms in biotransformation enzymes for benzo[a]pyrene and related levels of benzo[a]pyrene-7,8-diol-9,10-epoxide-DNA adducts in Goeckerman therapy. AB - Goeckerman therapy (GT) for psoriasis combines the therapeutic effect of crude coal tar (CCT) and ultraviolet radiation (UVR). CCT contains polycyclic aromatic hydrocarbons, some of which can form DNA adducts that may induce mutations and contribute to carcinogenesis. The aim of our work was to evaluate the relationship between concentrations of benzo[a]pyrene-7,8-diol-9,10-epoxide-DNA adducts (BPDE-DNA adducts) and rs4646903 (CYP1A1 gene), rs1048943 (CYP1A1), rs1056836 (CYP1B1), rs1051740 (EPHX1), rs2234922 (EPHX1) and rs8175347 (UGT1A1) polymorphic sites, and GSTM1 null polymorphism in 46 patients with chronic stable plaque psoriasis who underwent GT. The level of BPDE-DNA adducts was determined using the OxiSelect BPDE-DNA Adduct ELISA Kit. Polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis (rs4646903, rs1048943, rs1051740, and rs2234922), fragment analysis (rs8175347), real-time PCR (rs1056836), and digital droplet PCR polymorphism (GSTM1) were used. CYP1B1*1/*1 wild-type subjects and CYP1B1*3/*1 heterozygotes for rs1056836 formed significantly higher amounts of BPDE-DNA adducts than CYP1B1*3/*3 homozygotes (p=0.031 and p=0.005, respectively). Regarding rs1051740, individuals with EPHX1*3/*1 heterozygosity revealed fewer adducts than EPHX1*1/*1 wild-type subjects (p=0.026). Our data suggest that CYP1B1/EPHX1 genotyping could help to predict the risk of DNA damage and to optimize doses of coal tar and UVR exposure in psoriatic patients in whom GT was applied. PMID- 27188525 TI - Structure-function characterization of the human mitochondrial thiamin pyrophosphate transporter (hMTPPT; SLC25A19): Important roles for Ile(33), Ser(34), Asp(37), His(137) and Lys(291). AB - Thiamin plays a critical role in cellular energy metabolism. Mammalian cells obtain the vitamin from their surroundings, converted it to thiamin pyrophosphate (TPP) in the cytoplasm, followed by uptake of TPP by mitochondria via a carrier mediated process that involves the MTPPT (product of the SLC25A19 gene). Previous studies have characterized different physiological/biological aspects of the human MTPPT (hMTPPT), but less is known about structural features that are important for its function. Here, we used a protein-docking model ("Phyre2" and "DockingServer") to predict residues that may be important for function (substrate recognition) of the hMTPPT; we also examined the role of conserved positively-charged residues predicted ("PRALINE") to be in the trans-membrane domains (TMDs) in uptake of the negatively-charged TPP. Among the six residues predicted by the docking model (i.e., Thr(29), Arg(30), Ile(33), Ser(34), Asp(37) and Phe(298)), only Ile(33), Ser(34) and Asp(37) were found to be critical for function. While no change in translational efficiency/protein stability of the Ser(34) mutant was observed, both the Ile(33) and Asp(37) mutants showed a decrease in this parameter(s); there was also a decrease in the expression of the latter two mutants in mitochondria. A need for a polar residue at position 34 of the hMTPPT was evident. Our findings with the positively-charged residues (i.e., His(82), His(137), Lys(231) and Lys(291)) predicted in the TMD showed that His(137) and Lys(291) are important for function (via a role in proper delivery of the protein to mitochondria). These investigations provide important information about the structure-function relationship of the hMTPPT. PMID- 27188528 TI - Screening pi-conjugated bridges of organic dyes for dye-sensitized solar cells with panchromatic visible light harvesting. AB - Developing highly efficient organic dyes with panchromatic visible light harvesting for dye-sensitized solar cells (DSSCs) is still one of the most important scientific challenges. Here, we design a series of phenothiazine derivative organic dyes with donor-pi-acceptor (D-pi-A) structure using density functional theory (DFT) and time-dependent DFT (TDDFT) based on experimentally synthesized typical SH-6 organic dyes. Results indicate that the newly designed BUCT13 - BUCT30 dyes show smaller HOMO-LUMO energy gaps, higher molar extinction coefficients and obvious redshifts compared to the SH-6 dye, and the maximum absorption peaks of eight dyes are greater than 650 nm among the newly designed dyes. In particular, BUCT27 exhibits a 234 nm redshift and the maximum molar extinction coefficient with an increment of about 80% compared to the SH-6 dye. BUCT19 exhibits not only a 269 nm redshift and higher molar extinction coefficient with an increment of about 50% compared to the SH-6 dye, but the extremely broad absorption spectrum covering the entire visible range up to the near-IR region of 1200 nm. It is expected that this work can provide a new strategy and guidance for the investigation of these dye-sensitized devices. PMID- 27188527 TI - HIV infection. AB - More than 75 million people worldwide have been infected with human immunodeficiency virus (HIV), and there are now approximately 37 million individuals living with the infection. Untreated HIV replication causes progressive CD4(+) T cell loss and a wide range of immunological abnormalities, leading to an increased risk of infectious and oncological complications. HIV infection also contributes to cardiovascular disease, bone disease, renal and hepatic dysfunction and several other common morbidities. Antiretroviral drugs are highly effective at inhibiting HIV replication, and for individuals who can access and adhere to these drugs, combination antiretroviral therapy leads to durable (and probably lifelong) suppression of viral replication. Viral suppression enables immune recovery and the near elimination of the risk for developing acquired immune deficiency syndrome (AIDS). Despite effective treatment, HIV-infected individuals have a higher than expected risk of heart, bone, liver, kidney and neurological disease. When used optimally by an infected (or by an uninfected) person, antiretroviral drugs can virtually eliminate the risk of HIV transmission. Despite major advances in prevention sciences, HIV transmission remains common in many vulnerable populations, including men who have sex with men, injection drug users and sex workers. Owing to a lack of widespread HIV testing and the costs and toxicities associated with antiretroviral drugs, the majority of the infected population is not on effective antiretroviral therapy. To reverse the pandemic, improved prevention, treatment and implementation approaches are necessary. PMID- 27188526 TI - Long-term outcome of peroral endoscopic myotomy for achalasia treatment in a 9 year-old female patient. AB - Achalasia is a primary motility disorder with incomplete lower esophageal sphincter relaxation; it has an annual incidence of 0.11 cases per 100 000 children. Peroral endoscopic myotomy (POEM) is a new endoscopic treatment method for achalasia. Reports about POEM in pediatric patients are rare. We herein report the case of a 9-year-old female patient with achalasia who underwent POEM. The patient underwent endoscopic balloon dilatation because medication was not effective at a previous hospital; however, endoscopic balloon dilatation was not effective either. She then underwent successful POEM upon admission at our hospital. The patient was symptom-free at 2 years postoperatively with no signs of esophagitis in the absence of proton-pump inhibitor therapy. PMID- 27188530 TI - Early physical and motor development of mouse offspring exposed to valproic acid throughout intrauterine development. AB - Clinical research has identified developmental delay and physical malformations in children prenatally exposed to the antiepileptic drug (AED) valproic acid (VPA). However, the early signs of neurodevelopmental deficits, their evolution during postnatal development and growth, and the dose effects of VPA are not well understood. The present study aimed to examine the influence of maternal exposure to a wide dose range (50, 100, 200 and 400mg/kg/day) of VPA during breeding and gestation on early physical and neuromotor development in mice offspring. Body weight gain, eye opening, the surface righting reflex (SRR) and tail suspension test (TST) were examined in the offspring at postnatal days 5, 10 and 15. We observed that: (1) all tested doses of VPA reduced the body weight of the offspring and the timing of eye opening; (2) offspring exposed to VPA displayed immature forms of righting and required more time to complete the SRR; (3) latency for the first immobilization in the TST is shorter in offspring exposed to higher doses of VPA; however, mice in all groups exposed to VPA exhibited atypical changes in this parameter during the examined period of maturation; (4) irregularities in swinging and curling activities were observed in animals exposed to higher doses of VPA. This study points to delayed somatic development and postponed maturation of the motor system in all of the offspring prenatally exposed to VPA, with stronger effects observed at higher doses. The results implicate that the strategy of continuous monitoring of general health and achievements in motor milestones during the early postnatal development in prenatally VPA-exposed offspring, irrespectively of the dose applied, could help to recognize early developmental irregularities. PMID- 27188529 TI - Positive Selection on a Regulatory Insertion-Deletion Polymorphism in FADS2 Influences Apparent Endogenous Synthesis of Arachidonic Acid. AB - Long chain polyunsaturated fatty acids (LCPUFA) are bioactive components of membrane phospholipids and serve as substrates for signaling molecules. LCPUFA can be obtained directly from animal foods or synthesized endogenously from 18 carbon precursors via the FADS2 coded enzyme. Vegans rely almost exclusively on endogenous synthesis to generate LCPUFA and we hypothesized that an adaptive genetic polymorphism would confer advantage. The rs66698963 polymorphism, a 22-bp insertion-deletion within FADS2, is associated with basal FADS1 expression, and coordinated induction of FADS1 and FADS2 in vitro. Here, we determined rs66698963 genotype frequencies from 234 individuals of a primarily vegetarian Indian population and 311 individuals from the US. A much higher I/I genotype frequency was found in Indians (68%) than in the US (18%). Analysis using 1000 Genomes Project data confirmed our observation, revealing a global I/I genotype of 70% in South Asians, 53% in Africans, 29% in East Asians, and 17% in Europeans. Tests based on population divergence, site frequency spectrum, and long-range haplotype consistently point to positive selection encompassing rs66698963 in South Asian, African, and some East Asian populations. Basal plasma phospholipid arachidonic acid (ARA) status was 8% greater in I/I compared with D/D individuals. The biochemical pathway product-precursor difference, ARA minus linoleic acid, was 31% and 13% greater for I/I and I/D compared with D/D, respectively. This study is consistent with previous in vitro data suggesting that the insertion allele enhances n-6 LCPUFA synthesis and may confer an adaptive advantage in South Asians because of the traditional plant-based diet practice. PMID- 27188531 TI - PrPC expression and calpain activity independently mediate the effects of closed head injury in mice. AB - The normal cellular prion protein (PrPC) is a sialoglycoprotein with a glycophosphatidylinositol anchor and expressed in highest levels within the CNS particularly at neuronal synapses. This membrane-bound protein is involved with many cell functions including cell signaling and neuroprotection. Calpains are calcium-activated cysteine proteases that typically undergo controlled activation. PrPC is a calpain substrate and is neurotoxic if it undergoes aberrant processing with cytosol accumulation. Following traumatic brain injury (TBI), there is an abnormal influx of Ca+2 and overactivation of calpains resulting in neuronal dysfunction and cell death. We investigated whether PrPC expression and calpain activity have an effect on, or are affected by, TBI. PrPC expression in the hippocampus, cortex and cerebellum of WT and Tga20 (PrPC overexpression) mice were unchanged after closed head injury (CHI). Further, PrPC in WT and Tga20 mice was resistant to TBI-induced calpain proteolysis. CHI induced calpain activation resulted in breakdown products (BDPs) of alphaII spectrin (SBDPs) and GFAP (GBDP-44K) in all brain regions and mouse lines. CHI caused significant increases in SBDP145, GFAP and GBDP-44K when compared to sham. With few exceptions, the calpain inhibitor, SNJ-1945, reduced SBDP145 and GBDP 44K levels. Behavioral studies suggested that PrPC and calpain independently affect learning and memory. Overall, we conclude that: (i) there is SNJ-1945 sensitive calpain activation in both neuron and glial cells following CHI, (ii) closed head trauma is not affected by, nor does it have an influence on, PrPC expression, and (iii) PrPC expression plays a minor role, if any, in CHI-induced calpain activation in vivo. PMID- 27188534 TI - Does industry self-regulation protect young people from exposure to alcohol marketing? A review of compliance and complaint studies. AB - BACKGROUND AND AIMS: Exposure to alcohol marketing is considered to be potentially harmful to adolescents. In addition to statutory regulation, industry self-regulation is a common way to protect adolescents from alcohol marketing exposures. This paper critically reviews research designed to evaluate the effectiveness of the alcohol industry's compliance procedures to manage complaints when alcohol marketing is considered to have violated a self regulatory code. METHODS: Peer-reviewed papers were identified through four literature search engines: PubMed, SCOPUS, PsychINFO and CINAHL. Non-peer reviewed reports produced by public health agencies, alcohol research centers, non-governmental organizations, government research centers and national industry advertising associations were also included. RESULTS: The search process yielded three peer-reviewed papers, seven non-peer reviewed reports published by academic institutes and non-profit organizations and 20 industry reports. The evidence indicates that the complaint process lacks standardization across countries, industry adjudicators may be trained inadequately or biased and few complaints are upheld against advertisements pre-determined to contain violations of a self regulatory code. CONCLUSIONS: The current alcohol industry marketing complaint process used in a wide variety of countries may be ineffective at removing potentially harmful content from the market-place. The process of determining the validity of complaints employed by most industry groups appears to suffer from serious conflict of interest and procedural weaknesses that could compromise objective adjudication of even well-documented complaints. In our opinion the current system of self-regulation needs major modifications if it is to serve public health objectives, and more systematic evaluations of the complaint process are needed. PMID- 27188535 TI - Obstructive sleep apnoea syndrome. AB - Obstructive sleep apnoea syndrome (OSAS) is a common clinical condition in which the throat narrows or collapses repeatedly during sleep, causing obstructive sleep apnoea events. The syndrome is particularly prevalent in middle-aged and older adults. The mechanism by which the upper airway collapses is not fully understood but is multifactorial and includes obesity, craniofacial changes, alteration in upper airway muscle function, pharyngeal neuropathy and fluid shift towards the neck. The direct consequences of the collapse are intermittent hypoxia and hypercapnia, recurrent arousals and increase in respiratory efforts, leading to secondary sympathetic activation, oxidative stress and systemic inflammation. Excessive daytime sleepiness is a burden for the majority of patients. OSAS is also associated with cardiovascular co-morbidities, including hypertension, arrhythmias, stroke, coronary heart disease, atherosclerosis and overall increased cardiovascular mortality, as well as metabolic dysfunction. Whether treating sleep apnoea can fully reverse its chronic consequences remains to be established in adequately designed studies. Continuous positive airway pressure (CPAP) is the primary treatment modality in patients with severe OSAS, whereas oral appliances are also widely used in mild to moderate forms. Finally, combining different treatment modalities such as CPAP and weight control is beneficial, but need to be evaluated in randomized controlled trials. For an illustrated summary of this Primer, visit: http://go.nature.com/Lwc6te. PMID- 27188532 TI - Platelet sequestration and activation during GalTKO.hCD46 pig lung perfusion by human blood is primarily mediated by GPIb, GPIIb/IIIa, and von Willebrand Factor. AB - BACKGROUND: Here, we ask whether platelet GPIb and GPIIb/IIIa receptors modulate platelet sequestration and activation during GalTKO.hCD46 pig lung xenograft perfusion. METHODS: GalTKO.hCD46 transgenic pig lungs were perfused with heparinized fresh human blood. Results from perfusions in which alphaGPIb Fab (6B4, 10 mg/l blood, n = 6), alphaGPIIb/IIIa Fab (ReoPro, 3.5 mg/l blood, n = 6), or both drugs (n = 4) were administered to the perfusate were compared to two additional groups in which the donor pig received 1-desamino-8-d-arginine vasopressin (DDAVP), 3 MUg/kg (to pre-deplete von Willebrand Factor (pVWF), the main GPIb ligand), with or without alphaGPIb (n = 6 each). RESULTS: Platelet sequestration was significantly delayed in alphaGPIb, alphaGPIb+DDAVP, and alphaGPIb+alphaGPIIb/IIIa groups. Median lung "survival" was significantly longer (>240 vs. 162 min reference, p = 0.016), and platelet activation (as CD62P and betaTG) were significantly inhibited, when pigs were pre-treated with DDAVP, with or without alphaGPIb Fab treatment. Pulmonary vascular resistance rise was not significantly attenuated in any group, and was associated with residual thromboxane and histamine elaboration. CONCLUSIONS: The GPIb-VWF and GPIIb/IIIa axes play important roles in platelet sequestration and coagulation cascade activation during GalTKO.hCD46 lung xenograft injury. GPIb blockade significantly reduces platelet activation and delays platelet sequestration in this xenolung rejection model, an effect amplified by adding alphaGPIIb/IIIa blockade or depletion of VWF from pig lung. PMID- 27188536 TI - The impact of the codelivery of drug-siRNA by trimethyl chitosan nanoparticles on the efficacy of chemotherapy for metastatic breast cancer cell line (MDA-MB-231). AB - High-mobility group protein two (HMGA2), a nonhistone nuclear-binding protein and its downregulators; vimentin, matrix metallopeptidase-9 (MMP-9), and E-cadherin are shown to contribute to tumor progression and metastasis. Thus, in this study, we checked simultaneous delivery of HMGA-2 siRNA and the anticancer drug doxorubicin to enhance the anticancer treatment effects. For this purpose, we used MTT assay and real-time polymerase chain reaction (RT-PCR). Our results showed that dual delivery of Dox and HMGA-2 siRNA by trimethyl chitosan (TMC) significantly inhibited breast cancer cells growth. Additionally, the delivery of siRNA significantly silenced HMGA-2, vimentin, and MMP9 mRNAs, but led to overexpression of E-cadherin mRNA. PMID- 27188537 TI - Hepatitis B Virus Replication in CD34+ Hematopoietic Stem Cells From Umbilical Cord Blood. AB - BACKGROUND Hepatitis B virus (HBV) is a hepatotropic virus that can infect extrahepatic tissue. Whether hematopoietic stem cells (HSCs) can be infected by HBV and serve as a potential virus reservoir is still unknown. In this study, the susceptibility of CD34+ HSCs to HBV was investigated. MATERIAL AND METHODS Cord blood-derived CD34+ HSCs were exposed to HBV in vitro, and immunocytochemistry, transmission electron microscopy, and RT-PCR were used to identify viral-related proteins and specific viral genomic sequences. Then, CD34+ HSCs were challenged by different titers of HBV, and intracellular and supernatant HBV DNA, and hepatitis B surface antigen (HBsAg) levels, were examined. In addition, CD34+ peripheral blood stem cells (PBSCs) from chronic HBV carriers were isolated and cultured, and HBV DNA levels were measured. RESULTS HBV-infected CD34+ cells showed positive signals for HBsAg by DAB staining and TRITC staining, and HBV particles were identified. RT-PCR results showed that the 403 bp PCR products corresponding to the amplified hepatitis B S gene fragment were observed in CD34+ HSCs infected by HBV. In addition, supernatant and intracellular HBV DNA increased with the proliferation of CD34+ HSCs. Similar results were obtained from intracellular HBsAg quantification tests. In addition, HBV DNA levels both in cells and in supernatants of CD34+ PBSCs increased proportionally, and the increments of HBV DNA in the supernatants paralleled those found in cells. CONCLUSIONS HBV can replicate in CD34+ HSCs in cord blood or peripheral blood of chronic HBV carriers. PMID- 27188538 TI - Antibiotic prescribing in public and private practice: a cross-sectional study in primary care clinics in Malaysia. AB - BACKGROUND: Antibiotic overuse is driving the emergence of antibiotic resistance worldwide. Good data on prescribing behaviours of healthcare providers are needed to support antimicrobial stewardship initiatives. This study examined the differences in antibiotic prescribing rates of public and private primary care clinics in Malaysia. METHODS: We used data from the National Medical Care Survey (NMCS), a nationwide cluster sample of Malaysian public and private primary care clinics in 2014. NMCS contained demographic, diagnoses and prescribing from 129 public clinics and 416 private clinics. We identified all encounters who were prescribed antibiotic and analyse the prescribing rate, types of antibiotics, and diagnoses that resulted in antibiotic. RESULTS: Five thousand eight hundred ten encounters were prescribed antibiotics; antibiotic prescribing rate was 21.1 % (public clinics 6.8 %, private clinics 30.8 %). Antibiotic prescribing was higher in private clinics where they contributed almost 87 % of antibiotics prescribed in primary care. Upper respiratory tract infection (URTI) was the most frequent diagnosis in patients receiving antibiotic therapy and accounted for 49.2 % of prescriptions. Of the patients diagnosed with URTI, 46.2 % received antibiotic treatment (public 16.8 %, private 57.7 %). Penicillins, cephalosporins and macrolides were the most commonly prescribed antibiotics and accounted for 30.7, 23.6 and 16.0 % of all antibiotics, respectively. More recently available broad spectrum antibiotics such as azithromycin and quinolones were more frequently prescribed in private clinics. CONCLUSIONS: Antibiotic prescribing rates are high in both public and private primary care settings in Malaysia, especially in the latter. This study provides evidence of excessive and inappropriate antibiotic prescribing for self-limiting conditions. These data highlights the needs for more concerted interventions targeting both prescribers and public. Improvement strategies should focus on reducing inappropriate prescribing. PMID- 27188540 TI - Osteological Observations on the Alytid Anura Latonia nigriventer with Comments on Functional Morphology, Biogeography, and Evolutionary History. AB - The Hula Painted Frog (Latonia nigriventer) is a rare frog species endemic to the Hula Valley, Israel. The species is the sole relict of a clade that was widespread mainly in Europe from the Oligocene until the beginning of the Pleistocene. The osteological characteristics of L. nigriventer are described based on X-ray microtomography scans of extant specimens and Pleistocene bones from the Hula Valley, to elucidate the evolutionary history of Alytidae and more specifically of Latonia. Based on the osteological description of L. nigriventer, we now better understand the differences, between Latonia and its sister taxon Discoglossus. They differ mainly in their cranial structure with the reinforced skull of Latonia having powerful jaws. Latonia nigriventer can achieve great force while closing its jaws, due to increased adductor muscle insertion surfaces as expressed by the presence of an additional paracoronoid process and an enlarged upper margin of the postero-lateral wall of the lower jaw. In addition, a wider pterygoid fossa and higher canthus postero-lateralis of the frontoparietal, compared to that of Discoglossus, also suggest the presence of well-developed adductor muscles. Furthermore, L. nigriventer have particularly strong skulls as expressed by: long articulations between different skull elements, interdigitation in the contact area between the nasals and between nasals and the frontoparietals, and fused frontoparietals. Both males and females L. nigriventer have very robust forelimbs, as indicated by well-developed medial crests of the humerus. Based on limited eastern Mediterranean paleontological data, we can only suspect that the dispersal of Latonia into the Levant from Asia Minor occurred at some point during the Miocene or later. The first appearance of L. nigriventer in the Hula Valley, its current habitat, dates to approximately 780 thousand years ago at the archaeological site of Gesher Benot Ya'aqov. J. Morphol. 277:1131-1145, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27188539 TI - Could refuge theory and rivers acting as barriers explain the genetic variability distribution in the Atlantic Forest? AB - The Atlantic Forest is one of the most species-rich ecoregions in the world. The historical origins of this richness and the evolutionary processes that produced diversification and promoted speciation in this ecosystem remain poorly understood. In this context, focusing on Passiflora contracta, an endemic species from the Atlantic Forest distributed exclusively at sea level along forest edges, this study aimed to characterize the patterns of genetic variability and explore two hypotheses that attempt to explain the possible causes of the genetic diversity in this region: the refuge and riverine barrier theories. We employed Bayesian methods combined with niche modeling to identify genetically homogeneous groups, to determine the diversification age, and identify long-term climate stability areas to species survival. The analyses were performed using molecular markers from nuclear and plastid genomes, with samples collected throughout the entire geographic distribution of the species, and comparisons with congeners species. The results indicated that populations were genetically structured and provided evidence of demographic stability. The molecular markers indicated the existence of a clear structure and the presence of five homogeneous groups. Interestingly, the separation of the groups coincides with the geographical locations of local rivers, corroborating the hypothesis of rivers acting as barriers to gene flow in this species. The highest levels of genetic diversity and the areas identified as having long-term climate stability were found in the same region reported for other species as a possible refuge area during the climatic changes of the Quaternary. PMID- 27188541 TI - HBP Builder: A Tool to Generate Hyperbranched Polymers and Hyperbranched Multi Arm Copolymers for Coarse-grained and Fully Atomistic Molecular Simulations. AB - Computer simulation has been becoming a versatile tool that can investigate detailed information from the microscopic scale to the mesoscopic scale. However, the crucial first step of molecular simulation is model building, particularly for hyperbranched polymers (HBPs) and hyperbranched multi-arm copolymers (HBMCs) with complex and various topological structures. Unlike well-defined polymers, not only the molar weight of HBPs/HBMCs with polydispersity, but the HBPs/HBMCs with the same degree of polymerization (DP) and degree of branching (DB) also have many possible topological structures, thus making difficulties for user to build model in molecular simulation. In order to build a bridge between model building and molecular simulation of HBPs and HBMCs, we developed HBP Builder, a C language open source HBPs/HBMCs building toolkit. HBP Builder implements an automated protocol to build various coarse-grained and fully atomistic structures of HBPs/HBMCs according to user's specific requirements. Meanwhile, coarse grained and fully atomistic output structures can be directly employed in popular simulation packages, including HOOMD, Tinker and Gromacs. Moreover, HBP Builder has an easy-to-use graphical user interface and the modular architecture, making it easy to extend and reuse it as a part of other program. PMID- 27188542 TI - Updates on baseline characteristics of the omega-3 fatty acids (Fish oils) and Aspirin in Vascular access OUtcomes in REnal Disease (FAVOURED) study. PMID- 27188545 TI - A Brief Review of West Nile Virus Biology. AB - West Nile virus (WNV) is an arbovirus with increased global incidence in the last decade. It is also a major cause of human encephalitis in the USA. WNV is an arthropod-transmitted virus that mainly affects birds but humans become infected as incidental dead-end hosts which can cause outbreaks in naive populations. The main vectors of WNV are mosquitoes of the genus Culex, which preferentially feed on birds. As in many other arboviruses, the characteristics that allow Flaviviruses like WNV to replicate and transmit to different hosts are encrypted in their genome, which also contains information for the production of structural and nonstructural proteins needed for host cell infection. WNV and other Flaviviruses have developed different strategies to establish infection, replication, and successful transmission. Most of these strategies include the diversion of the host's immune responses away from the virus. In this review, we describe the molecular structure and protein function of WNV with emphasis on protein involvement in the modulation of antiviral immune responses. PMID- 27188544 TI - Synthetic MUC1 Antitumor Vaccine Candidates with Varied Glycosylation Pattern Bearing R/S-configured Pam3 CysSerLys4. AB - The Toll-like receptor 2 ligand Pam3 CysSer is of particular interest for the construction synthetic vaccines because of its ability to stimulate of the innate immune system. Such vaccines usually comprise Pam3 CysSer with the natural R configuration at the glycerol 2-position. Pam3 CysSer peptide vaccines with natural configuration have been shown to be more efficient than the corresponding R/S diastereomers. In order to clarify whether the effect of the configuration of Pam3 Cys on the immune response also applies to glycopeptide vaccines, MUC1 glycopeptide-lipopeptide vaccines bearing either R- or R/S-configured Pam3 CysSerLys4 were compared for their immunological effects. In order to find out whether glycosylated MUC1 tandem repeat domains comprise not only B-cell epitopes but also T-cell epitopes, two-component vaccines containing the Pam3 CysSerLys4 lipopeptide and MUC1 glycopeptides with various glycosylation patterns were synthesized, and their immune reactions in mice were studied. PMID- 27188543 TI - Body image and eating behavior in young adults born preterm. AB - OBJECTIVE: Previous studies have suggested that people born preterm have increased rates of eating disorders (ED). However, a recent study suggested lower levels of ED-related symptoms in the extreme group of adults born preterm with very low birth weight (<1,500 g). We examined symptoms related to EDs in adults born early (<34 weeks of gestational age) or late (34 to <37 weeks of gestational age) preterm. METHODS: We studied young adults (mean age 24.1 years) from two birth cohorts: ESTER (Northern Finland 1985-1989) and AYLS (Uusimaa, Finland, 1985-1986). Of the participants, 185 were born early preterm, 348 late preterm, and 637 were term-born controls (N = 1,170). They completed three subscales of the Eating Disorder Inventory (EDI)-2, including Drive for Thinness (DT), Body Dissatisfaction (BD), and Bulimia (B). Group differences were examined by linear regression. RESULTS: Young women born early preterm scored 4.1 points (95% CI 8.0, -0.2, P =.04) lower in summed EDI subscale scores than women born at term, when adjusted for age and cohort. This difference was observed also in DT and BD but not for B subscales. The differences persisted after adjustments for current, pre- and neonatal characteristics. We did not observe differences in EDI scores among men or women born late preterm when compared to controls. DISCUSSION: Women born early preterm have significantly fewer symptoms related to EDs in early adulthood when compared to their peers born at term, which may protect from developing an ED. (c) 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:572 580). PMID- 27188546 TI - Overview of West Nile Virus Transmission and Epidemiology. AB - West Nile virus (WNV) is a mosquito-borne flavivirus that can cause mild-to severe disease in humans and horses. WNV was first documented in Uganda in 1937 and passed through the majority of Africa, West Asia, and Europe before arriving in the USA (with infections in New York City in 1999). After the spread of the virus on the US east coast, it traveled westward, northward, and southward through the USA and into Central and South America. WNV can cause fever, rashes, nausea, vomiting, and potentially neuroinvasive disease or death. The virus is sustained through a mosquito-bird-mosquito cycle and there are many species that are competent vectors. Unfortunately, there are no vaccines and the only treatment is supportive care. This chapter highlights the epidemiology and transmission of WNV and provides insight into some of the challenges of controlling WNV disease. PMID- 27188547 TI - Propagation and Titration of West Nile Virus on Vero Cells. AB - The propagation and titration of viruses are key virological techniques. Unlike other flaviviruses, such as the dengue viruses, West Nile virus (WNV) grows and plaques very efficiently on Vero cells, usually inducing strong cytopathic effect (CPE) and forming clear plaques. Here, we outline the steps for propagating WNV from culture supernatant stocks and homogenized organ/mosquito samples, as well as for determining virus titers in samples by serial-dilution plaque assay using neutral red or crystal violet stains. PMID- 27188548 TI - Generating West Nile Virus from an Infectious Clone. AB - WNV infectious clones are valuable tools for elucidating WNV biology. Nevertheless, relatively few infectious WNV clones have been generated because their construction is hampered by the instability of flaviviral genomes. More recently, advances in cloning techniques as well as the development of several two-plasmid WNV infectious clone systems have facilitated the generation of WNV infectious clones. Here we described a protocol for recovering WNV from a two plasmid system. In this approach, large quantities of these constructs are digested with restriction enzymes to produce complementary restriction sites at the 3' end of the upstream fragment and the 5' end of the downstream fragment. These fragments are then annealed to produce linear template for in vitro transcription to synthesize infectious RNA. The resulting RNA is transfected into cells and after several days WNV is recovered in the culture supernatant. This method can be used to generate virus from infectious clones encoding high- and low-pathogenicity strains of WNV, as well as chimeric virues. PMID- 27188550 TI - Lessons from the Murine Models of West Nile Virus Infection. AB - West Nile virus (WNV), a mosquito-borne, single positive-stranded RNA virus, has been the leading cause of arboviral encephalitis in the U.S. and other parts of the world over the past decade. Up to 50 % of WNV convalescent patients were reported to have long-term neurological sequelae or chronic kidney diseases. However, there are neither antiviral drugs nor vaccines available for humans. The underlying mechanism of the long-term sequelae is not clearly understood either. Animal models have been an effective tool to investigate viral pathogenesis and host immunity in humans. Here, we will review several commonly used murine models of WNV infection. PMID- 27188552 TI - Examination of West Nile Virus Neuroinvasion and Neuropathogenesis in the Central Nervous System of a Murine Model. AB - West Nile virus (WNV) is a neurotropic virus that causes inflammation and neuronal loss in the Central Nervous System leading to encephalitis and death. In this chapter, detailed methods to detect WNV in the murine brain tissue by quantitative real-time polymerase chain reaction and viral plaque assays are described. Determination of WNV neuropathogenesis by Hematoxylin and Eosin staining and immunohistochemical procedures are provided. In addition, TUNEL assays to determine neuronal loss during WNV neuropathogenesis are discussed in detail. Collectively, the methods mentioned in this chapter provide an overview to understand neuroinvasion and neuropathogenesis in a murine model of WNV infection. PMID- 27188551 TI - Exploration of West Nile Virus Infection in Mouse Models. AB - West Nile virus (WNV) causes neurological diseases by penetrating the central nervous system (CNS)-an immune-privileged system. Although the CNS residential cells can produce antiviral immune responses, the blood leukocytes are required to contain virus spread. However, infiltrating leukocytes may also contribute to immunopathology if they overreact. Thus analyses of WNV infectivity and leukocyte numbers in the CNS are critical for understanding of WNV pathogenesis in experimental mouse models. Here I describe two basic assays for quantification of viral titers and infiltrating leukocytes in the mouse brain after WNV infection. PMID- 27188549 TI - Functional Analysis of West Nile Virus Proteins in Human Cells. AB - West Nile Virus (WNV) lineage 2 strains have been responsible for large outbreaks of neuroinvasive disease in the United States and Europe between 1999 and 2012. Different strains in this lineage have previously been shown to produce either severe or mild neuroinvasive disease in mice. Phylogenetic and amino acid comparisons between highly or less virulent lineage 2 strains have demonstrated that the nonstructural (NS) gene(s) were most variable. However, the roles of some of the NS proteins in virus life cycle are unknown. The aim of this chapter is to describe simple computational and experimental approaches that can be used to: (1) explore the possible roles of the NS proteins in virus life cycle and (2) test whether the subtle amino acid changes in WNV NS gene products contributed to the evolution of more virulent strains. The computational approaches include methods based on: (1) sequence similarity, (2) sequence motifs, and (3) protein membrane topology predictions. Highlighted experimental procedures include: (1) isolation of viral RNA from WNV-infected cells, (2) cDNA synthesis and PCR amplification of WNV genes, (3) cloning into GFP expression vector, (4) bacterial transformation, (5) plasmid isolation and purification, (6) transfection using activated dendrimers (Polyfect), and (7) immunofluorescence staining of transfected mammalian cells. PMID- 27188556 TI - Safe Handling of West Nile Virus in the Insectary. AB - Working with West Nile virus (WNV) in the insectary requires specific facilities and protocols to prevent laboratory-acquired infection. Here, we review case reports of individuals infected with members of the Flaviviridae while performing biomedical research in traditional laboratories and insectaries. We highlight the most common transmission route and summarize recommendations for facilities and protocols designed to prevent laboratory-acquired infections. PMID- 27188554 TI - Methodology for Identifying Host Factors Involved in West Nile Virus Infection. AB - The West Nile virus (WNV) infection is a major medical problem for humans and some domesticated animals. WNV infection of host cells involves the interplay of the virus with several host factors. Identification of the host factors impacting on WNV infection can enhance our understanding of virus infection mechanisms, host immune defense mechanisms, and also reveal novel host targets that can be developed as antivirals. RNA interference (RNAi) is a highly efficient genetic tool to discover host genes involved in WNV infection at a genome scale. Here, we describe a protocol for conducting human genome wide RNAi screen to discover novel host factors associated with WNV infection of human cells. PMID- 27188557 TI - Techniques for Experimental Infection of Mosquitoes with West Nile Virus. AB - West Nile virus is a typical mosquito-borne flavivirus, and it is transmitted between mosquitoes and birds in nature. As an incidental host, humans are susceptible to WNV infection. WNV infection in humans can result in fever, meningitis, and encephalitis. Approved human vaccines or therapies are not available for WNV infection. In this chapter, we focus on the techniques for WNV infection and detection in mosquitoes. The technical details include: (1) WNV infection in cell culture; (2) Mosquito rearing; (3) WNV infection in mosquitoes via thoracic microinjection; (4) Detection of WNV infection in mosquitoes; (5) Determination of WNV M.I.D50 in mosquitoes; (6) WNV infection in mosquitoes via membrane blood feeding; (7) WNV infection via blood feeding on mice; (8) Immunofluorescence staining of WNV infected mosquito tissues. PMID- 27188555 TI - ELISA and Neutralization Methods to Measure Anti-West Nile Virus Antibody Responses. AB - Measurements of humoral immune responses to West Nile virus (WNV) infection in mouse or other animal models are valuable components of basic laboratory investigations to assess immunogenicity of candidate vaccines or to evaluate seroconversion following challenge with WNV. Here, we outline the steps for screening or titrating of total antibodies by indirect enzyme linked immunosorbent assay (ELISA) as well as assessment of neutralizing antibody titers by immunofocus detection. PMID- 27188558 TI - Field Surveillance Methods for West Nile Virus. AB - Surveillance of West Nile virus (WNV) in populations of mosquitoes or sentinel animals is of primary importance when assessing the risks to human health posed by naturally circulating WNV. In this chapter we focus on methods for detection of both WNV and its enzootic transmission. Methods for virus detection include CDC mini light trap, CDC gravid trap, and dead bird surveillance. Methods for transmission detection include passive box traps, chicken-baited traps, and sentinel chickens. PMID- 27188553 TI - In Vitro and In Vivo Blood-Brain Barrier Models to Study West Nile Virus Pathogenesis. AB - The blood-brain barrier (BBB), a specialized interface between the peripheral blood circulation and the central nervous system, specifically regulates molecular and cellular flux between the two. It plays a critical role in the maintenance of brain hemostasis. The BBB restricts the entry of pathogens into the brain, and thus its permeability is a critical factor that determines their central effects. Once the permeability of BBB is compromised, it has serious implications in the etiology of many brain pathologies including West Nile virus (WNV) disease. In this chapter, we describe protocols for preparation, maintenance, infection and permeability measurement of monolayer and bilayer in vitro BBB models to study WNV pathogenesis. We also describe Evans blue dye assay, a well-established method to test vascular permeability in vivo after WNV infection. PMID- 27188560 TI - Field Methods and Sample Collection Techniques for the Surveillance of West Nile Virus in Avian Hosts. AB - Avian hosts play an important role in the spread, maintenance, and amplification of West Nile virus (WNV). Avian susceptibility to WNV varies from species to species thus surveillance efforts can focus both on birds that survive infection and those that succumb. Here we describe methods for the collection and sampling of live birds for WNV antibodies or viremia, and methods for the sampling of dead birds. Target species and study design considerations are discussed. PMID- 27188559 TI - Detection Protocols for West Nile Virus in Mosquitoes, Birds, and Nonhuman Mammals. AB - West Nile virus is the most widespread mosquito-borne virus in the world, and the most common cause of encephalitis in the USA. Surveillance for this medially important mosquito-borne pathogen is an important part of public health practice. Here we present protocols for testing environmental samples such as mosquitoes, nonvertebrate mammals, and birds for this virus, including RT-PCR, virus isolation in cell culture, and antigenic assays, as well as serologic assays for antibody detection. PMID- 27188563 TI - An Overview of Current Approaches Toward the Treatment and Prevention of West Nile Virus Infection. AB - The persistence of West Nile virus (WNV) infections throughout the USA since its inception in 1999 and its continuous spread throughout the globe calls for an urgent need of effective treatments and prevention measures. Although the licensing of several WNV vaccines for veterinary use provides a proof of concept, similar efforts on the development of an effective vaccine for humans remain still unsuccessful. Increased understanding of biology and pathogenesis of WNV together with recent technological advancements have raised hope that an effective WNV vaccine may be available in the near future. In addition, rapid progress in the structural and functional characterization of WNV and other flaviviral proteins have provided a solid base for the design and development of several classes of inhibitors as potential WNV therapeutics. Moreover, the therapeutic monoclonal antibodies demonstrate an excellent efficacy against WNV in animal models and represent a promising class of WNV therapeutics. However, there are some challenges as to the design and development of a safe and efficient WNV vaccine or therapeutic. In this chapter, we discuss the current approaches, progress, and challenges toward the development of WNV vaccines, therapeutic antibodies, and antiviral drugs. PMID- 27188565 TI - We must remain nurse-focused. PMID- 27188564 TI - Efficient synthesis of longer Abeta peptides via removable backbone modification. AB - Longer amyloid-beta (Abeta) peptides (43 to 49 amino acids) play essential roles in the pathology of Alzheimer's disease (AD). The difficulty in the preparation of longer Abeta peptides is still an obstacle to elucidate their roles in AD. Herein we report a robust and efficient strategy for the chemical synthesis of longer Abeta peptides (Abeta48 and Abeta49). A key feature of this method is the installation of removable Arg4-tagged backbone modification groups into the hydrophobic region of Abeta. This modification can improve the handling properties of the purification, ligation and mass characterization of longer Abeta peptides. The practicability of the new method has been demonstrated by the successful synthesis of Abeta48 and Abeta49 peptides. PMID- 27188561 TI - Statistical Tools for the Interpretation of Enzootic West Nile virus Transmission Dynamics. AB - Interpretation of enzootic West Nile virus (WNV) surveillance indicators requires little advanced mathematical skill, but greatly enhances the ability of public health officials to prescribe effective WNV management tactics. Stepwise procedures for the calculation of mosquito infection rates (IR) and vector index (VI) are presented alongside statistical tools that require additional computation. A brief review of advantages and important considerations for each statistic's use is provided. PMID- 27188567 TI - Exploring recruitment issues in stroke research: a qualitative study of nurse researchers' experiences. AB - AIM: To explore the practice of experienced stroke nurse researchers to understand the issues they face in recruiting participants. BACKGROUND: Participant recruitment is one of the greatest challenges in conducting clinical research, with many trials failing due to recruitment problems. Stroke research is a particularly difficult area in which to recruit; however various strategies can improve participation. DISCUSSION: Analysis revealed three main types of problems for recruiting participants to stroke research: those related to patients, those related to the nurse researcher, and those related to the study itself. Impairments affecting capacity to consent, the acute recruitment time frame of most stroke trials, paternalism by nurse researchers, and low public awareness were especially pertinent. CONCLUSION: The disabling nature of a stroke, which often includes functional and cognitive impairments, and the acute stage of illness at which patients are appropriate for many trials, make recruiting patients particularly complex and challenging. IMPLICATIONS FOR PRACTICE: An awareness of the issues surrounding the recruitment of stroke patients may help researchers in designing and conducting trials. Future work is needed to address the complexities of obtaining informed consent when patient capacity is compromised. PMID- 27188569 TI - Fundamentals of estimating sample size. AB - BACKGROUND: Estimating sample size is an integral requirement in the planning stages of quantitative studies. However, although abundant literature is available that describes techniques for calculating sample size, many are in depth and have varying degrees of complexity. AIM: To provide an overview of four basic parameters that underpin the determination of sample size and to explain sample-size estimation for three study designs common in nursing research. DISCUSSION: Researchers can estimate basic sample size if they have a comprehension of four parameters, such as significance level, power, effect size, and standard deviation (for continuous data) or event rate (for dichotomous data). In this paper, these parameters are applied to determine sample size for the following well-established study designs: a comparison of two independent means, the paired mean study design and a comparison of two proportions. CONCLUSION: An informed choice of parameter values to input into estimates of sample size enables the researcher to derive the minimum sample size required with sufficient power to detect a meaningful effect. An understanding of the parameters provides the foundation from which to generalise to more complex size estimates. It also enables more informed entry of required parameters into sample size software. IMPLICATIONS FOR PRACTICE: Underpinning the concept of evidence based practice in nursing and midwifery is the application of findings that are statistically sound. Researchers with a good understanding of parameters, such as significance level, power, effect size, standard deviation and event rate, are enabled to calculate an informed sample size estimation and to report more clearly the rationale for applying any particular parameter value in sample size determination. PMID- 27188566 TI - Undertaking healthcare research with vulnerable populations: lessons to share. PMID- 27188568 TI - Exploring how to increase response rates to surveys of older people. AB - AIM: To address the special considerations that need to be taken into account when collecting data from older people in healthcare research. BACKGROUND: An objective of all research studies is to ensure there is an adequate sample size. The final sample size will be influenced by methods of recruitment and data collection, among other factors. There are some special considerations that need to be addressed when collecting data among older people. DATA SOURCES: Quantitative surveys of people aged 60 or over in 2009-2014 were analysed using statistical methods. A quantitative study of patients aged 75 or over in an emergency department was used as an example. REVIEW METHODS: A methodological approach to analysing quantitative studies concerned with older people. CONCLUSION: The best way to ensure high response rates in surveys involving people aged 60 or over is to collect data in the presence of the researcher; response rates are lowest in posted surveys and settings where the researcher is not present when data are collected. Response rates do not seem to vary according to the database from which information about the study participants is obtained or according to who is responsible for recruitment to the survey. Implications for research/practice To conduct coherent studies with older people, the data collection process should be carefully considered. PMID- 27188570 TI - Participatory action research for women with anorexia nervosa. AB - AIM: To discuss the application of the principles of participatory action research (PAR) in a project that developed and evaluated a mentor-mentee support programme for women with anorexia nervosa. BACKGROUND: A programme was developed and implemented in which mentors and mentees participated in workshops, social activities and focus groups that sought to support and develop resilience for those experiencing anorexia nervosa. DISCUSSION: PAR principles were mirrored in the programme, paying respect to the views and needs of each participant, an open trajectory to possible conclusions and a continuous feedback cycle. Mentees had a sense of empowerment, ownership of the programme and hope that recovery was possible. It allowed their voices to be heard and provided them with belief they could begin new relationships and friendships. CONCLUSION: The principles of PAR suited a project aimed at developing self-determination and resilience in women with anorexia nervosa. IMPLICATIONS FOR RESEARCH/PRACTICE: PAR would be readily transferable to a number of mental health settings where empowerment is of paramount concern. PMID- 27188562 TI - Role of Immune Aging in Susceptibility to West Nile Virus. AB - West Nile virus (WNV) can cause severe neuroinvasive disease in humans and currently no vaccine or specific treatments are available. As aging is the most prominent risk factor for WNV, age-related immune dysregulation likely plays an essential role in host susceptibility to infection with WNV. In this review, we summarize recent findings in effects of aging on immune responses to WNV infection. In particular, we focus on the age-dependent dysregulation of innate immune cell types-neutrophils, macrophages, and dendritic cells-in response to WNV infection, as well as age-related alterations in NK cells and gammadelta T cells that may associate with increased WNV susceptibility in older people. We also highlight two advanced technologies, i.e., mass cytometry and microRNA profiling, which significantly contribute to systems-level study of immune dysregulation in aging and should facilitate new discoveries for therapeutic intervention against WNV. PMID- 27188572 TI - Variation of Kozinets' framework and application to nursing research. AB - BACKGROUND: Online communities are new sites for undertaking research, with their textual interactions providing a rich source of data in real time. 'Ethnonetnography' is a research methodology based on ethnography that can be used in these online communities. In this study, the researcher and a specialist breast care nurse (SBCN) were immersed in the online community, adding to patients' breast cancer care and providing a nursing research component to the community. AIM: To examine Kozinets' ( 2010 ) framework for ethnonetnography and how it may be varied for use in a purpose-built, disease-specific, online support community. DISCUSSION: The online community provided an area where members could communicate with each other. Kozinets' ( 2010 ) framework was varied in that the research was carried out in a purpose-built community opf which an SBCN was a member who could provide support and advice. The application of the ethnonetnographic methodology has wide implications for clinical nursing practice and research. CONCLUSION: Ethnonetnography can be used to study disease-specific communities in a focused manner and can provide immediate benefits through the inclusion of an expert nurse and contemporaneous application of research findings to patient care. IMPLICATIONS FOR PRACTICE: With ethical permission and the permission of online community members, nurse researchers can enter already established online communities. Ethnonetnography is ideally suited to nursing research as it provides the immediacy of evidence-based interaction with an expert nurse. These real-time responses improve support for those experiencing a critical life event. PMID- 27188571 TI - Capturing the carer's experience: a researcher's reflections. AB - AIM: To reflect on the methodological challenges of conducting a study exploring the effects on quality of life of being an informal carer for a person with palliative heart failure, as well as the factors that influence a carer's perception of caring. BACKGROUND: There are multi-faceted influences on the positive and negative effects of being a carer for a patient with palliative heart failure. By conducting a mixed methods study the aim was to examine and explore similarities and differences of the phenomenon of being a carer. DATA SOURCES: Quantitative data obtained from the Family Quality of Life Questionnaire (FAMQOL), and qualitative data obtained from 14 interviews with informal carers of patients living with palliative heart failure. REVIEW METHODS: The study was conducted as part of a PhD, University of Sheffield, and the supervisory team reviewed the research process throughout the study. DISCUSSION: The study had a two-phase sequential mixed methods design. A sample of carers was recruited from heart failure nurse service caseloads in a UK urban setting. Carers were invited to complete the Family Quality of Life Questionnaire, a tool developed for carers of patients with heart failure. Participants were also asked to provide contact details if they were willing to be interviewed for the second phase of the study. CONCLUSION: The study highlights important methodological considerations for recruiting carers. As the intention was to begin the analysis of the questionnaires before beginning the second phase of the study, the researcher was compelled to consider how integration was maintained and how to improve access to carers for research. IMPLICATIONS FOR PRACTICE: The complexities associated with the population in this study led the researcher to use a pragmatic design to address research questions. When reflecting on the research and the challenges associated with recruiting to the quantitative phase of the study, the researcher used an iterative approach to meet the unfolding complexities. Such an approach could prove beneficial for mixed methods studies that aim to engage with hard to reach populations. PMID- 27188576 TI - Non-small-cell lung cancer. AB - Lung cancer is one of the most frequently diagnosed cancers and is the leading cause of cancer-related death worldwide. Non-small-cell lung cancer (NSCLC), a heterogeneous class of tumours, represents approximately 85% of all new lung cancer diagnoses. Tobacco smoking remains the main risk factor for developing this disease, but radon exposure and air pollution also have a role. Most patients are diagnosed with advanced-stage disease owing to inadequate screening programmes and late onset of clinical symptoms; consequently, patients have a very poor prognosis. Several diagnostic approaches can be used for NSCLC, including X-ray, CT and PET imaging, and histological examination of tumour biopsies. Accurate staging of the cancer is required to determine the optimal management strategy, which includes surgery, radiochemotherapy, immunotherapy and targeted approaches with anti-angiogenic monoclonal antibodies or tyrosine kinase inhibitors if tumours harbour oncogene mutations. Several of these driver mutations have been identified (for example, in epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK)), and therapy continues to advance to tackle acquired resistance problems. Also, palliative care has a central role in patient management and greatly improves quality of life. For an illustrated summary of this Primer, visit: http://go.nature.com/rWYFgg. PMID- 27188575 TI - Axitinib in the Treatment of Head and Neck Malignancies. AB - Head and neck cancers (thyroid and head and neck squamous cell carcinoma (HNSCC)) are relatively common malignancies and although often curable at initial diagnosis, treatment of advanced disease is palliative in intent. There is a scarcity of treatment options, many of which are traditionally associated with significant toxicities and poor survival. Translational studies have identified numerous dysregulated pathways amongst head and neck cancers, including VEGFR and EGFR, highlighting the potential role for targeted therapies. This review details the role of VEGFR in both head and neck cancers and discusses recent trials utilizing axitinib, a multi-tyrosine kinase inhibitor with targets including VEGFR-1, -2, and -3. The article discusses the toxicity data as well as ongoing clinical trials. PMID- 27188580 TI - Episodic Abdominal Pain Characteristics Are Not Associated with Clinically Relevant Improvement of Health Status After Cholecystectomy. AB - BACKGROUND: Cholecystectomy is the therapy of first choice in patients with uncomplicated symptomatic cholecystolithiasis, but it remains unclear which patients truly benefit in terms of health status improvement. Patients generally present with episodic abdominal pain of varying frequency, duration, and intensity. We assessed whether characteristics of abdominal pain episodes are determinants of clinically relevant improvement of health status after cholecystectomy. METHODS: In a post hoc analysis of a prospective multicenter cohort study, patients of >=18 years of age with uncomplicated symptomatic cholecystolithiasis subjected to cholecystectomy were included. Preoperatively, patients received a structured interview and a questionnaire consisting of the visual analogue scale (VAS; range 0-100) and gastrointestinal quality of life index (GIQLI). At 12 weeks after cholecystectomy, the GIQLI was again administered. Logistic regression analyses were performed to determine significant associations. RESULTS: Questionnaires were sent to 261 and returned by 166 (63.6 %) patients (128 females, mean age at surgery 49.5 +/- 13.8). A total of 131 (78.9 %) patients reported a clinically relevant improvement of health status. The median (interquartile range) frequency, duration, and intensity of abdominal pain episodes were 0.38 (0.18-0.75) a week, 4.00 (2.00 8.00) hours, and 92 (77-99), respectively. None of the characteristics was associated with a clinically relevant improvement of health status at 12 weeks after cholecystectomy. CONCLUSIONS: Characteristics of abdominal pain episodes cannot be used to inform patients with symptomatic cholecystolithiasis who are skeptic about the timing of cholecystectomy for optimal benefit. Timing of cholecystectomy should therefore be based on other characteristics and preferences. PMID- 27188582 TI - The occurrence of the strongylid nematodes Kalicephalus brachycephalus, K. bungari and K. indicus in snake species from Hunan Province, China. AB - Kalicephalus is a genus of strongylid nematodes infecting snakes and causing serious diseases and even death when it is complicated with secondary bacterial infections. The infection of snakes with Kalicephalus has been reported in many countries in the world. However, little information is available on the prevalence of Kalicephalus in snakes in China. In the present study, the prevalence of Kalicephalus in snakes was investigated. The worms were examined, counted and identified to species according to existing keys and descriptions. Three species of Kalicephalus, namely K. indicus, K. bungari and K. brachycephalus, were found in six species of snakes (Elaphe carinata, Zaocys dhumnade, Naja najaatra, Elaphe taeniura, Bungarus multicinctus and Dinodon rufozonatum). The total prevalence of Kalicephalus in snakes in Hunan Province was 39.7%. The most common species was K. indicus, with the highest prevalence 72.8%, followed by K. bungari (24.0%). The prevalence of K. brachycephalus was 0.9%. This is the first report on the prevalence of Kalicephalus species in snakes in China, and the findings have important implications for the control of Kalicephalus infections in snakes in China. PMID- 27188577 TI - Disruption of Notch signaling aggravates irradiation-induced bone marrow injury, which is ameliorated by a soluble Dll1 ligand through Csf2rb2 upregulation. AB - Physical and chemical insult-induced bone marrow (BM) damage often leads to lethality resulting from the depletion of hematopoietic stem and progenitor cells (HSPCs) and/or a deteriorated BM stroma. Notch signaling plays an important role in hematopoiesis, but whether it is involved in BM damage remains unclear. In this study, we found that conditional disruption of RBP-J, the transcription factor of canonical Notch signaling, increased irradiation sensitivity in mice. Activation of Notch signaling with the endothelial cell (EC)-targeted soluble Dll1 Notch ligand mD1R promoted BM recovery after irradiation. mD1R treatment resulted in a significant increase in myeloid progenitors and monocytes in the BM, spleen and peripheral blood after irradiation. mD1R also enhanced hematopoiesis in mice treated with cyclophosphamide, a chemotherapeutic drug that induces BM suppression. Mechanistically, mD1R increased the proliferation and reduced the apoptosis of myeloid cells in the BM after irradiation. The beta chain cytokine receptor Csf2rb2 was identified as a downstream molecule of Notch signaling in hematopoietic cells. mD1R improved hematopoietic recovery through up regulation of the hematopoietic expression of Csf2rb2. Our findings reveal the role of Notch signaling in irradiation- and drug-induced BM suppression and establish a new potential therapy of BM- and myelo-suppression induced by radiotherapy and chemotherapy. PMID- 27188583 TI - Inbreeding depression under mixed outcrossing, self-fertilization and sib-mating. AB - BACKGROUND: Biparental inbreeding, mating between two relatives, occurs at a low frequency in many natural plant populations, which also often have substantial rates of self-fertilization. Although biparental inbreeding is likely to influence the dynamics of inbreeding depression and the evolution of selfing rates, it has received limited theoretical attention in comparison to selfing. The only previous model suggested that biparental inbreeding can favour the maintenance of stable intermediate selfing rates, but made unrealistic assumptions about the genetic basis of inbreeding depression. Here we extend a genetic model of inbreeding depression, describing nearly recessive lethal mutations at a very large number of loci, to incorporate sib-mating. We also include a constant component of inbreeding depression modelling the effects of mildly deleterious, nearly additive alleles. We analyze how observed rates of sib mating influence the mean number of heterozygous lethals alleles and inbreeding depression in a population reproducing by a mixture of self-fertilization, sib mating and outcrossing. We finally use the ensuing relationship between equilibrium inbreeding depression and population selfing rate to infer the evolutionarily stable selfing rates expected under such a mixed mating system. RESULTS: We show that for a given rate of inbreeding, sib-mating is more efficient at purging inbreeding depression than selfing, because homozygosity of lethals increases more gradually through sib-mating than through selfing. Because sib-mating promotes the purging of inbreeding depression and the evolution of selfing, our genetic model of inbreeding depression also predicts that sib-mating is unlikely to maintain stable intermediate selfing rates. CONCLUSIONS: Our results imply that even low rates of sib-mating affect plant mating system evolution, by facilitating the evolution of selfing via more efficient purging of inbreeding depression. Alternative mechanisms, such as pollination ecology, are necessary to explain stable mixed selfing and outcrossing. PMID- 27188581 TI - Stool-based biomarkers of interstitial cystitis/bladder pain syndrome. AB - Interstitial cystitis/bladder pain syndrome (IC) is associated with significant morbidity, yet underlying mechanisms and diagnostic biomarkers remain unknown. Pelvic organs exhibit neural crosstalk by convergence of visceral sensory pathways, and rodent studies demonstrate distinct bacterial pain phenotypes, suggesting that the microbiome modulates pelvic pain in IC. Stool samples were obtained from female IC patients and healthy controls, and symptom severity was determined by questionnaire. Operational taxonomic units (OTUs) were identified by16S rDNA sequence analysis. Machine learning by Extended Random Forest (ERF) identified OTUs associated with symptom scores. Quantitative PCR of stool DNA with species-specific primer pairs demonstrated significantly reduced levels of E. sinensis, C. aerofaciens, F. prausnitzii, O. splanchnicus, and L. longoviformis in microbiota of IC patients. These species, deficient in IC pelvic pain (DIPP), were further evaluated by Receiver-operator characteristic (ROC) analyses, and DIPP species emerged as potential IC biomarkers. Stool metabolomic studies identified glyceraldehyde as significantly elevated in IC. Metabolomic pathway analysis identified lipid pathways, consistent with predicted metagenome functionality. Together, these findings suggest that DIPP species and metabolites may serve as candidates for novel IC biomarkers in stool. Functional changes in the IC microbiome may also serve as therapeutic targets for treating chronic pelvic pain. PMID- 27188585 TI - Delayed healing of oral mucosa in a diabetic rat model: Implication of TNF-alpha, IL-1beta and FGF-2. PMID- 27188586 TI - Bosentan reverses the hypoxia-induced downregulation of the bone morphogenetic protein signaling in pulmonary artery smooth muscle cells. AB - AIMS: Pulmonary hypertension (PH) is a common complication of chronic hypoxic lung diseases. Bone morphogenetic protein (BMP) and endothelin-1 signaling pathways have been shown to be altered in hypoxic PH and to play crucial roles in the associated pulmonary artery remodeling. We, therefore, aimed to study the potential link between hypoxia and the alteration of BMP and endothelin-1 signaling observed in pulmonary artery smooth muscle cells (PA-SMCs) in hypoxic PH. MATERIALS AND METHODS: Human PA-SMCs were treated with hypoxia-mimetic agent cobalt chloride (CoCl2; 100MUM), with or without pretreatment with a dual endothelin receptor antagonist bosentan (10MUM). Expressions of preproendothelin 1 (PPET1), BMP type 2 receptor (BMPR-2), and one BMP signaling target gene, the inhibitor of DNA binding 1 (ID1) were evaluated by real time quantitative polymerase chain reaction. BMP2-treated PA-SMCs were assessed for Smad1/5/8 signaling activation by Western Blotting. KEY FINDINGS: Treatment of PA-SMCs with CoCl2 increased PPET1 gene expression, while it did not alter expressions of endothelin converting enzyme, endothelin receptor type A or type B. Hypoxia mimetic agent CoCl2 decreased the expressions of BMPR-2 and ID1 maximally after 3 and 6-hour treatment respectively, while CoCl2 treatment progressively increased noggin expression. Bosentan pretreatment restored expressions of BMPR-2 and ID1, as well as the activation (by phosphorylation) of Smad1/5/8 signaling induced by BMP2. SIGNIFICANCE: Hypoxia induces the downregulation of the BMP signaling in PA SMCs, at least, partly through the endothelin system. In hypoxic PH, increased endothelin-1 production might therefore contribute to the altered BMP signaling and subsequent PA-SMC hyperplasia. PMID- 27188590 TI - Portal hypertensive polyps, a new entity? AB - We present a case of a 62 year old woman with history of liver cirrhosis secondary to autoimmune hepatitis, with portal hypertension and coagulopathy. Gastroscopy findings were a polypoid and polylobed lesions in the gastric antrum. These were removed and the pathological study described hyperplastic polyps with edema, vascular congestion and hyperplasia of smooth muscle, corresponding to "portal hypertensive polyps" (PHP). PMID- 27188589 TI - Clinicopathologic Features of Inverted Serrated Lesions of the Large Bowel. AB - BACKGROUND/AIMS: Serrated lesions (SLs) of the large bowel occasionally manifest as inverted growths with endophytic expansion within the muscularis mucosa. The aims of this investigation were to investigate the incidence of inverted SLs (ISLs) among SLs and to describe the clinicopathologic features. METHODS: We reviewed the colonoscopy records from 2006 to 2014 at our institution and identified cases of endoscopically or surgically resected SLs, including hyperplastic polyps (HPs), sessile serrated adenomas/polyps (SSA/Ps) and traditional serrated adenomas (TSAs). The incidence of ISLs among the SLs and their colonoscopic findings were investigated retrospectively. RESULTS: There were 35 HPs in 30 patients, 80 SSA/Ps in 65 patients and 70 TSAs in 65 patients. The incidence of ISLs was significantly higher among SSA/Ps (8.8%) and HPs (5.7%) than among TSAs (0%; p = 0.04). A predominant right-sided location, a flat elevated configuration with a central depression and round-open pit pattern or expanded crypt openings were characteristic of ISLs of the SSA/P type. CONCLUSIONS: Right-sided flat lesions with a central depression and round or expanded crypts are indicative of ISLs of the SSA/P type. PMID- 27188588 TI - Housekeeping promoter 5'pcmah-2 of pig CMP-N-acetylneuraminic acid hydroxylase gene for NeuGc expression. AB - In the present study, we isolated pCMAH house-keeping promoter regions (Ph), which are responsible for transcriptional regulation and which are located upstream of the alternative transcript pcmah-2. Luciferase reporter assays using serial construction of each deleted promoter demonstrated that the Ph promoter was highly active in pig-derived kidney PK15. Ph promoter of pcmah lacked a TATA box, but contained three putative Sp1 binding sites. Mutations of these Sp1 binding sites always resulted in the reduction of luciferase activities in Ph 334. In addition, treatment with mithramycin A (25-100 nM) decreased the luciferase activities of the Ph promoters and NeuGc expression in a dose dependent manner. Electrophoretic mobility shift assay analysis revealed that the probes containing each Sp1 binding site bound to Sp1. Taken together, the results indicate that Sp1 bind to their putative binding sites on the Ph promoter regions of pcmah and positively regulate the promoter activity in pig kidney cells. Interspecies comparison of 5'UTRs and 5'flanking regions shows high homology between pig and cattle, and Sp1 binding sites existing in genomic regions corresponding Ph region are evolutionally conserved. PMID- 27188579 TI - A Historical Perspective on Sports Concussion: Where We Have Been and Where We Are Going. AB - The approach to sports concussion diagnosis and management has been evolving at an unprecedented rate over the last several years. So much so, that committees at all level of sports have implemented concussion protocols and made adjustments to certain league rules in an effort to minimize the risk of head injury. With this newfound attention has come an even greater push by the scientific community to address the many questions that remain. The aim of this review article is to present the topic of sports concussion by means of discreet eras. It begins by introducing the very first mentions of concussion, dating back to ancient Greece, to present day, highlighting important periods along the way. It then goes on to review emerging scientific data, from biomarkers and serum studies, to imaging modalities, and brain networking. All of which will hopefully contribute to both the diagnostic and therapeutic approach to sports concussion. PMID- 27188591 TI - Successful balloon overtube-guided colorectal endoscopic submucosal dissection by a gastroscope. AB - Colorectal ESD can achieve en-bloc resection. However, cecum, hepatic and splenic flexures are difficult locations because of unstable scope maneuvers and narrow working space. In these cases, balloon overtube-guided ESD may confer a better approach, improving the access to the lesion and scope manoeuvres. This overtube has a large outer diameter and enables the use of a therapeutic gastroscope. The procedure can also facilitate traction-assisted techniques allowing a high-rate of en-bloc resections. In addition, large specimens can be easily retrieved through. PMID- 27188584 TI - Spin-texture inversion in the giant Rashba semiconductor BiTeI. AB - Semiconductors with strong spin-orbit interaction as the underlying mechanism for the generation of spin-polarized electrons are showing potential for applications in spintronic devices. Unveiling the full spin texture in momentum space for such materials and its relation to the microscopic structure of the electronic wave functions is experimentally challenging and yet essential for exploiting spin orbit effects for spin manipulation. Here we employ a state-of-the-art photoelectron momentum microscope with a multichannel spin filter to directly image the spin texture of the layered polar semiconductor BiTeI within the full two-dimensional momentum plane. Our experimental results, supported by relativistic ab initio calculations, demonstrate that the valence and conduction band electrons in BiTeI have spin textures of opposite chirality and of pronounced orbital dependence beyond the standard Rashba model, the latter giving rise to strong optical selection-rule effects on the photoelectron spin polarization. These observations open avenues for spin-texture manipulation by atomic-layer and charge carrier control in polar semiconductors. PMID- 27188593 TI - Family planning services in a tertiary hospital in a semi-urban area of south western Nigeria: Uptake and determinants of contraceptive use. AB - An audit of 954 family planning clinic attendees, who received counselling from 2006 to 2010, was conducted at the only federal government owned tertiary hospital in Ondo state, Nigeria. Of these, 637 (66.8%) accepted a family planning method: 47.6% chose injectables, 23.2% intrauterine device, 19.5% oral contraceptive pills, 4.4% barrier methods, 3.3% implants and 2% tubal ligation. Clients who had some primary education [OR: 2.79; (95% CI: 1.14-6.84; p < 0.05] had statistically significant higher odds of accepting any contraceptive method while those with elevated blood pressure at first visit [OR: 0.23; 95% CI: 0.12 0.45; p < 0.001] and those with previous episode(s) of induced abortion OR: 0.57; 95% CI: 0.43-0.76; p < 0.001] had statistically significant lower odds of using any method. Concerted efforts at increasing uptake is advocated to bridge the gap between client counselling and uptake. PMID- 27188592 TI - Endoscopic diagnosis of asymptomatic perforation of colonic diverticulum. AB - Colonic perforation as complication of acute diverticulitis is a relatively frequent pathology and generally very symptomatic. Nevertheless, when it occurs in the mesenteric border the course can be indolent. PMID- 27188594 TI - Tunable Picosecond Laser Pulses via the Contrast of Two Reverse Saturable Absorption Phases in a Waveguide Platform. AB - How to enhance the optical nonlinearity of saturable absorption materials is an important question to improve the functionality of various applications ranging from the high power laser to photonic computational devices. We demonstrate the saturable absorption (SA) of VO2 film attributed to the large difference of optical nonlinearities between the two states of the phase-transition materials (VO2). Such VO2 film demonstrated significantly improved performance with saturation intensity higher than other existing ultrathin saturable absorbers by 3 orders due to its unique nonlinear optical mechanisms in the ultrafast phase change process. Owing to this feature, a Q-switched pulsed laser was fabricated in a waveguide platform, which is the first time to achieve picosecond pulse duration and maintain high peak power. Furthermore, the emission of this VO2 waveguide laser can be flexibly switched between the continuous-wave (CW) and pulsed operation regimes by tuning the temperature of the VO2 film, which enables VO2-based miniature laser devices with unique and versatile functions. PMID- 27188600 TI - A pseudo-icosahedral cage {Gd12} based on aminomethylphosphonate. AB - Reaction of (aminomethyl)phosphonic acid (ampH2) with a mixture of gadolinium and cobalt pivalates under solvothermal conditions, led to a pseudo-icosahedral cage {Gd12}, which shows a large magnetocaloric effect (MCE). PMID- 27188587 TI - Embryoglycan: a highly branched poly-N-acetyllactosamine in pluripotent stem cells and early embryonic cells. AB - Embryonal carcinoma cells, stem cells of teratocarcinomas, are pluripotent stem cells and also prototypes of embryonic stem cells. Embryonal carcinoma cells contain large amounts of a highly branched poly-N-acetyllactosamine called embryoglycan, which has a molecular weight of approximately 10,000 or greater, and is asparagine-linked. This glycan was found by analyses of fucose-labeled glycopeptides, and its characteristics were established by biochemical analyses. The content of embryoglycan progressively decreases during the in vitro differentiation of embryonal carcinoma cells. Embryoglycan is also abundant in mouse embryonic stem cells and preimplantation mouse embryos, and decreases during embryogenesis. Embryoglycan carries a number of carbohydrate markers of murine pluripotent stem cells. Lewis x markers, such as SSEA-1, 4C9 antigen, and binding sites for Lotus tetragonolobus agglutinin are of particular importance. 4C9 antigenicity requires clustering of Lewis x, best accomplished by poly-N acetyllactosamine branching, whereas SSEA-1 does not. Although in vivo evidence is lacking, these epitopes have been suggested to participate in cell-to-cell and cell-to-substratum adhesion. Other markers on embryoglycan include alpha galactosyl antigens such as ECMA-2, and binding sites for Dolichos biflorus agglutinin, the epitope of which is considered to be identical to Sda antigen, namely, GalNAcbeta1-4(NeuAcalpha2-3)Galbeta1-4GlcNAc. While embryoglycan is also present in human teratocarcinoma cells, the carbohydrate markers characterized in human pluripotent stem cells to date are largely carried by glycolipids and keratan sulfate. Information on embryoglycan and markers carried by it may assist in the development of new markers of human pluripotent stem cells and their progenies. PMID- 27188599 TI - Are there bad foods or just bad diets? PMID- 27188601 TI - Paenibacillus cisolokensis sp. nov., isolated from litter of a geyser. AB - A Gram-stain-positive, endospore-forming, aerobic and thermophilic bacterium, designated strain LC2-13AT, was isolated from Cisolok geyser, West Java, Indonesia, at 50 degrees C. The isolate was rod-shaped and motile by means of peritrichous flagella. The major cellular fatty acids were iso-C16 : 0, C16 : 0 and anteiso-C15 : 0 and the major quinone was menaquinone 7. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. The genomic DNA G+C content was 56.6 mol% and the major diagnostic diamino acid in the cell-wall peptidoglycan was meso-diaminopimelic acid. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that strain LC2-13AT is related most closely to Paenibacillus kobensis DSM 10249T (94.86 % similarity), Paenibacillus tarimensis SA-7-6T (94.77 %) and Paenibacillus barengoltzii SAFN-016T (94.77 %). On the basis of phenotypic, chemotaxonomic and phylogenetic evidence, strain LC2-13AT is affiliated to the genus Paenibacillus, but could be distinguished from recognized species of this genus. A novel species with the name Paenibacillus cisolokensis sp. nov. is thus proposed. The type strain is LC2-13AT (=UICC B-42T=NRRL B-65368T=DSM 101873T). PMID- 27188595 TI - Impaired Mobilization of Vascular Reparative Bone Marrow Cells in Streptozotocin Induced Diabetes but not in Leptin Receptor-Deficient db/db Mice. AB - Diabetes is associated with impaired mobilization of bone marrow stem/progenitor cells that accelerate vascularization of ischemic areas. This study characterized mobilization of vascular reparative bone marrow progenitor cells in mouse models of diabetes. Age-matched control or streptozotocin (STZ)-induced diabetic, and db/db mice with lean-controls were studied. Mobilization induced by G-CSF, AMD3100 or ischemia was evaluated by flow cytometric enumeration of circulating Lin(-)Sca-1(+)cKit(+) (LSK) cells, and by colony forming unit (CFU) assay. The circulating WBCs and LSKs, and CFUs were reduced in both models with a shorter duration (10-12 weeks) of diabetes compared to their respective controls. Longer duration of STZ-diabetes (>=20 weeks) induced impairment of G-CSF- or AMD3100 mobilization (P < 0.01, n = 8). In db/db mice, mobilization by G-CSF or AMD3100 was either increased or unaffected (P < 0.05, n = 6 to 8). Proliferation, migration, and ischemia-induced mobilization, of LSK cells were impaired in both models. Leptin receptor antagonist, PESLAN-1, increased G-CSF- or AMD3100 mobilization of WBCs and LSKs, compared to the untreated. Leptin increased basal WBCs, decreased basal and AMD3100-mobilized LSK cells, and had no effect on G CSF. These results suggest that mobilopathy is apparent in STZ-diabetes but not in db/db mice. Leptin receptor antagonism would be a promising approach for reversing diabetic bone marrow mobilopathy. PMID- 27188597 TI - Impact of individual metabolic risk components or its clustering on endothelial and smooth muscle cell function in men. AB - BACKGROUND: Impaired vasoreactivity is often observed in subjects with metabolic syndrome, a condition that includes the presence of a specific cluster of risk factors for obesity and cardiovascular disease. However, hierarchical causes in the impaired vasoreactivity have not been clarified. We evaluated the impact of individual metabolic risk components or its clustering under the condition of insulin resistance on endothelial and smooth muscle cell function. METHODS: Vascular reactivity to acetylcholine (Ach), with or without nitric oxide synthase (NOS) inhibitor N (G)-monomethyl-L-arginine (L-NMMA), or sodium nitroprusside (SNP) by forearm venous occlusion plethysmography and insulin sensitivity index (M mg/kg/min) in euglycemic clamp were measured in men without (n = 18, control group) or with (n = 19, metabolic syndrome group) metabolic syndrome. RESULTS: (1) Ach-induced maximal forearm blood flow (maxFBF) was impaired in subjects with metabolic syndrome. In particular, the NOS-dependent component of Ach-induced maxFBF was selectively decreased, while the NOS-independent component remained relatively unchanged. (2) Ach-induced maxFBF and ?Ach-induced maxFBF with L-NMMA were correlated with waist circumference, glucose, and triglycerides, and most strongly correlated with visceral fat area, adiponectin, and M. (3) Multivariate regression analysis indicated that individual metabolic risk components explained Ach-induced maxFBF by 4-21 %. Clustering of all metabolic risk components increased this to 35 %, and the presence of metabolic syndrome explained 30 %, indicating that defining metabolic syndrome can effectively predict impairment of endothelial dysfunction. CONCLUSIONS: Endothelial dysfunction was correlated with individual metabolic risk components, but more strongly with clustering of the components under a condition with low insulin sensitivity. We suggest that in subjects with metabolic syndrome, endothelial function is impaired by multiple cardiovascular risk factors exclusively when under the condition of insulin insensitivity and also that defining metabolic syndrome can effectively predict impairment of endothelial dysfunction. PMID- 27188602 TI - [The underlying mechanisms of overcoming EGFR-TKIs resistance by casein kinase 2 inhibitor]. AB - Nowadays, EGFR-TKIs are important treatment strategy in lung cancer, but the resistance to EGFR-TKIs remains an unsolved issue preventing the patients from further benefits. Recent studies have shown that casein kinase (CK2) plays an important role in carcinogenesis and development of cancer. CK2 inhibitor has also demonstrated anti-tumor effects. Here we reviewed the mechanism of EGFR-TKIs and the potential reasons of resistance. Interestingly, there is a crosstalk between CK2 and EGFR downstream signaling pathways, therefore, it may be possible that CK2 inhibitor can overcome the EGFR-TKIs resistance. PMID- 27188598 TI - Longitudinal brain structural alterations and systemic inflammation in obstructive sleep apnea before and after surgical treatment. AB - BACKGROUND: Systemic inflammation, neurocognitive impairments, and morphologic brain changes are associated with obstructive sleep apnea (OSA). Understanding their longitudinal evolution and interactions after surgical treatment provides clues to the pathogenesis of cognitive impairment and its reversibility. In the present study, we investigate clinical disease severity, systemic inflammation, cognitive deficits, and corresponding gray matter volume (GMV) changes in OSA, and the modifications following surgery. METHODS: Twenty-one patients with OSA (apnea-hypopnea index, AHI > 5) and 15 healthy volunteers (AHI < 5) underwent serial evaluation, including polysomnography, flow cytometry for leukocyte apoptosis categorization, cognitive function evaluation, and high-resolution brain scan. Disease severity, leukocyte apoptosis, cognitive function, and imaging data were collected to assess therapeutic efficacy 3 months after surgery. RESULTS: Pre-operatively, patients presented with worse cognitive function, worse polysomnography scores, and higher early leukocyte apoptosis associated with increased insular GMV. There was reduced GMV in the anterior cingulate gyrus before and after surgery in the cases compared to that in controls, suggesting an irreversible structural deficit. Post-operatively, there were significant improvements in different cognitive domains, including attention, executive and visuospatial function, and depression, and in early leukocyte apoptosis. There was also a significant decrease in GMVs after treatment, suggesting recovery from vasogenic edema in the precuneus, insula, and cerebellum. Improvement in early leukocyte apoptosis post-surgery predicted better recovery of precuneus GMV. CONCLUSIONS: In OSA, increased disease severity and systemic inflammation can alter GMV in vulnerable regions. Surgical treatment may improve disease severity and systemic inflammation, with subsequent recovery in brain structures and functions. PMID- 27188604 TI - [Treatment of liver cancer in vitro and in mice by monoclonal antibody targeting epithelial specific antigen-positive liver cancer stem cells in combination with cisplatin]. AB - OBJECTIVE: To investigate the biological characteristics of monoclonal antibodies against human liver cancer stem cells and its therapeutic effect in combination with cisplatin in the treatment of hepatocellular carcinoma. METHODS: Cell culture in serum-free medium and PKH26 staining were used to determine the existence of cancer stem cells in human liver Bel7402-V3 cell line. The co expression of antigen recognized by monoclonal antibody (McAb) 15D2 and epithelial specific antigen (ESA) and PKH26-positive cells in the Bel7402-V3 cells were detected by immunofluorescence assay. Serum-free suspension culture was used to detect the self-renewal ability of 15D2-positive Bel7402-V3 cells sorted by flow cytometry and the effect of 15D2 on the self-renewal ability of Bel7402-V3 cells. The effect of 15D2 on cisplatin resistance in the cells was examined by CCK8 method. The inhibitory effect of 15D2 combined with cisplatin on the transplanted tumor growth in mice was also observed. RESULTS: Single PKH26 positive cells were observed in the Bel7402-V3 cell spheroids cultured for 11 days. Immunofluorescence assay showed that the 15D2-recognized antigen could be conjugated with PKH26 and ESA and co-localized on Bel7402-V3 cells. The spheroid formation rate of 15D2-positive cells in serum-free medium was significantly higher than that of 15D2-negative cells [(30.4+/-3.4)% vs. (8.8+/-1.8)%, P<0.01]. The cisplatin resistance of 15D2-positive cells was obviously higher than that of 15D2-negative cells (IC50: 1.014 MUmol/L vs. 0.365 MUmol/L). McAb 15D2 significantly suppressed the spheroid formation of Bel7402-V3 cells, with an inhibition rate of 37.5%. McAb 15D2 also notably inhibited the cisplatin resistance of Bel7302-V3 cells. The IC50 was 0.211 MUg/ml in the 15D2 group and 0.325 MUg/ml in the control group. The mouse experiment showed that the tumor growth rates of 50 mg/kg, 25 mg/kg and 12.5 mg/kg 15D2-treatment groups were 82.6%, 71.4% and 60.0%, respectively; that of the 50 mg/kg 15D2 + cisplatin group was 91.0%, and that of the cisplatin monotherapy was 56.7%. CONCLUSION: McAb 15D2 is a functional monoclonal antibody targeting liver cancer stem cells, which could be a potential monoclonal antibody drug for the stem cell-targeted therapy of liver cancer. PMID- 27188603 TI - [Effect of bufalin on proliferation and apoptosis through ERK/RSK2 pathway in human esophageal carcinoma cell line xenografts in nude mice]. AB - OBJECTIVE: To investigate the effect of bufalin on proliferation and apoptosis through ERK/RSK2 pathway in esophageal squamous cell carcinoma xenografts in nude mice. METHODS: The subcutaneous xenograft model of esophageal cancer ECA109 cells in nude mice was established. The mice were divided into the model group, low dose bufalin group, medium-dose bufalin group, high-dose bufalin group, PD98059 group and combination group to evaluate the effect of bufalin on the xenografts. The morphology of xenografts was observed by microscopy. The cell apoptosis index of xenografts was detected by TUNEL assay. The expression of ERK and RSK2 mRNA of human ECA109 cell transplantation tumor in nude mice was examined by real-time quantitative PCR. The protein levels of ERK, p-ERK, RSK2, p-RSK2, GSK3beta, p GSK3beta, Bad and p-Bad in the xenografts were examined by Western blot and Immunohistochemistry. RESULTS: The tumor size of nude mice in the model group, low-dose bufalin group (BL), medium -dose bufalin group (BM), high-dose bufalin group (BH), PD98059 group and combined therapy group (BP) was (1.758+/-0.181) cm(3,) (1.680+/-0.150) cm(3,) (1.285+/-0.134) cm(3,) (0.873+/-0.095) cm(3,) (0.815+/-0.108) cm(3) and (0.530+/-0.104) cm(3,) respectively. Histological examination showed that the xenografts of each group had varying degrees of necrosis, and the most extensive necrosis was observed in the BP group. The TUNEL assay showed that the cell apoptosis index of xenografts in the model, BL, BM, BH, PD98059 and BP groups was (6.0+/-0.6)%, (11.0+/-0.7)%, (19.1+/-0.9)%, (25.1+/ 1.4)%, (20.0+/-1.2)% and (17.1+/-0.7)%, respectively, which is highest in the BH group. The real-time quantitative PCR results showed that the DeltaCT values of ERK mRNA in the model, BL, BM, BH, PD98059 and BP groups were 0.270+/-0.084, 0.293+/-0.081, 0.596+/-0.224, 0.857+/-0.183, 0.868+/-0.187 and 1.313+/-0.282, respectively. The DeltaCT values of RSK2 mRNA in the model, BL, BM, BH, PD98059 and BP groups were 0.340+/-0.062, 0.337+/-0.071, 0.642+/-0.226, 0.915+/-0.170, 0.923+/-0.176 and 1.413+/-0.269, respectively. The relative expression of ERK and RSK2 mRNA was gradually decreased. Western blot and immunohistochemistry results showed that the protein levels of ERK, RSK2 and Bad in each group were not significantly different (P>0.05). The protein levels of p-ERK in the model, BL, BM, BH, PD98059 and BP groups were 0.721+/-0.094, 0.695+/-0.095, 0.555+/-0.080, 0.388+/-0.052, 0.341+/-0.060, 0.235+/- 0.056, respectively. The median immunoreactivity scores of p-ERK in each group were 8, 8, 6, 4, 5 and 3. The protein levels of p-RSK2 in the model, BL, BM, BH, PD98059 and BP groups were 0.613+/-0.085, 0.612+/-0.084, 0.427+/-0.089, 0.305+/-0.056, 0.258+/-0.051, 0.158+/-0.058, respectively. The median immunoreactivity scores of p-RSK in each group were 8, 8, 5, 3, 3 and 1. The protein level of GSK3beta in the model, BL, BM, BH, PD98059 and BP groups were increased gradually, while the protein level of p-GSK3beta and p-Bad were decreased gradually. CONCLUSIONS: Bufalin exerts significant inhibitory effect on the esophageal squamous cell carcinoma xenogragts in nude mice. Bufalin may suppress the growth of xenogragts in nude mice by down-regulating the level of ERK and RSK2 phosphorylation, inhibit the proliferation of xenogragts via inactivating GSK3beta and promote apoptosis through down-regulation of p-Bad. PMID- 27188605 TI - [Inhibitory effect of imrecoxib combined with lobaplatin on tumor growth and lymph node metastasis of human lung cancer xenografts in nude mice]. AB - OBJECTIVE: To evaluate the inhibitory effect of imrecoxib combined with lobaplatin on tumor growth and lymph node metastasis of human lung adenocarcinoma xenografts in nude mice, and to explore its possible mechanisms. METHODS: Human lung cancer A549 cells were injected into Bal B/c nude mice subcutaneously. Twenty-eight healthy male nude mice were randomly divided into 4 groups: the control group, imrecoxib group, lobaplatin group and imrecoxib combined with lobaplatin group. Each group was treated with appropriate drugs and the tumor size was measured every five days. The expression of ezrin and E-cadherin protein was detected by immunohistochemistry and flow cytometry. Ezrin and E-cadherin mRNA were detected by real-time PCR. RESULTS: The tumor inhibition rates of imrecoxib group, lobaplatin group and combination group were 36.7%, 54.6% and 69.2%, respectively. The tumor volumes of imrecoxib group [(905.33+/-113.31) mm(3)] and combination group [(507.74+/-77.50) mm(3)] were significantly lower than that of the control group (1355.33+/-189.04) mm(3) (P<0.05), and the tumor weights were significantly reduced [(1.13+/-0.14) g, (0.63+/-0.10) g respectively] vs. (1.69+/-0.24) g (P<0.05). The expressions of ezrin protein and mRNA in the imrecoxib group and combined treatment group were significantly lower than that of the control group (136.53+/-35.52, 74.72+/-19.48 vs. 175.62+/-21.16 for protein expression level; 0.54+/-0.03, 0.36+/-0.03 vs. 1.02+/-0.02 for mRNA expression level, respectively, P<0.05 for both), while the expression of E cadherin protein and mRNA in the imrecoxib group and combined treatment group was significantly higher than that of the control group (253.78+/-38.87, 308.94+/ 24.67 vs. 213.66+/-30.31 for protein expression level; 2.19+/-0.02, 3.02+/-0.02 vs. 1.05+/-0.03 for mRNA expression level, respectively, P<0.05 for both). There was a significant negative correlation between ezrin protein and E-cadherin protein (r=-0.737, P<0.01), as well as between ezrin mRNA and E-cadherin mRNA (r= 0.977, P<0.01). CONCLUSIONS: Administration of imrecoxib combined with lobaphatin has inhibitory effects on the growth of non-small cell lung cancer xenografts and lymph node metastasis via down-regulated ezrin and upregulated E-cadherin. Imrecoxib and lobaplatin have a synergistic antitumor effect. PMID- 27188606 TI - [Expression of annexin A7 and its clinical significance in gastric carcinoma]. AB - OBJECTIVE: To investigate the expression of annexin A7 (ANXA7) in the differentiation and lymphatic metastasis of gastric cancer (GC), and to investigate the relationship between ANXA7 and biological characteristics of GC. METHODS: The clinicopathological data of 124 patients with gastric cancer who underwent surgical treatment in our hospital were retrospectively reviewed and analyzed. Immunohistochemical staining and Western blot were performed to analyze the expression of ANXA 7 in primary GC tissues. Logistic regression analysis was conducted to evaluate the association between ANXA7 expression level and differentiation of the GC. RESULTS: A total of 124 GC patients were enrolled in this study, and the expression rate of ANXA7 was 65.3% in the GC. The survival rate of ANXA7-positive patients was significantly lower than that in the patients with negative expression (P<0.001). The results of Cox regression analysis showed that the positive expression of ANXA7, submucosal confinement and pathological stage of GC were associated with poor clinical outcomes. The ratio of pixel density value of primary GC tissues with lymph node metastasis was significantly higher than those in the tissues without lymph node metastasis (0.51+/-0.07 vs. 0.39+/-0.06, P<0.001). ROC analysis showed a high area under the curve for the ratio of pixel density value of annexin A7 in the primary GC tissues. At a cut off level of >0.419, the ratio of pixel density value of ANXA7 exhibited a sensitivity of 91.2% and a specificity of 72.7% for detecting lymph node metastasis of GC. CONCLUSION: High annexin A7 expression is associated with poor differentiation of gastric cancer, and it may become a predictor for lymphatic metastasis of GC. PMID- 27188607 TI - [Effects of Rad9 mutants with impaired DNA mismatch repair function on tumorigenesis of colorectal cancer]. AB - OBJECTIVE: The aim of this study was to investigate the effects of Rad9 mutants with impaired DNA mismatch repair (MMR) function on the tumorigenesis of colorectal cancer. METHODS: The colorectal cancer tumor samples were collected from 100 patients. The mutation profiles of human Rad9 (hRad9) gene in these samples were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and sequencing. The plasmid of pFLAG-hRad9 (L101M) was constructed following the QuickChange mutagenesis procedure and transfected into mRad9-deleted mouse cells (mRad9(-/-) cells). The expression of hRad9 protein was measured by western blot analysis. The MMR activity in live cells was detected by flow cytometry using the reporter plasmid for MMR function. RESULTS: Mutation from Leu to Met at the residue 101 (L101M) of hRad9 gene was detected in 7 of the 100 samples. The mismatch repair efficiency of mRad9(-/-)+ L101M cells (mRad9-deleted mouse cells with ectopic expression of L101M hRad9 gene) was (34.0+/-5.6)%, which was significantly lower than that in the mRad9(-/-)+ hRad9 cells [mRad9-deleted mouse cells with ectopic expression of hRad9 gene, (48.0+/-7.5)%, P<0.05]. After N nitroso-N-methylurea (MNU) treatment, the survival rate of mRad9(-/-)+ L101M cells was (33.7+/-5.9)%, which was significantly higher than that in the mRad9(-/ )+ hRad9 cells [(21.3+/-4.7)%, P<0.05]. Thus, ectopic expression of L101M hRad9 gene resulted in significantly reduced MMR activity and increased resistance to MNU. Furthermore, ectopic expression of hRad9 gene with mutation at the target residues of post-translational modification in mRad9(-/-) cells also led to a reduced MMR activity. CONCLUSION: Rad9 mutants with impaired DNA mismatch repair function may promote tumorigenesis of colorectal cancer. PMID- 27188610 TI - [Relationship between circulating tumor cells and coagulation factors in primary lung cancer patients]. AB - OBJECTIVE: To investigate the relationship between the presence of circulating tumor cells (CTC) and the values of coagulation factors including D-dimer (D-D), fibrinogen (FIB) and platelet (PLT) in primary lung cancer patients. METHODS: Peripheral venous blood samples were collected from 79 patients with previously untreated primary lung cancer. The levels of D-D, FIB and PLT were detected. The CTCs were enriched by negative immunomagnetic separation with anti-CD45 antibody and then detected by immunocytochemistry with Anti-pan Cytokeratin antibody. The relationship between these parameters and clinicopathologic characteristics of the patients was analyzed. RESULTS: The levels of D-D, FIB and PLT were( 1.74+/ 2.04) mg/L, (3.51+/-1.46 )g/L, (311+/-139)*10(9)/L, respectively. The level of D D was associated with distant metastasis of lung cancer (P=0.046). The level of FIB was associated with clinical stage and distant metastasis (P<0.05). The level of PLT was associated with age, clinical stage and distant metastasis (all P<0.05). Among the 79 patients, there were 45 CTC-positive and 34 CTC-negative cases. The levels of D-D in the CTC-positive and CTC-negative groups were (2.31+/ 2.41)mg/L and (0.99+/-1.02)mg/L, those of FIB were (3.79+/-1.56)g/L and (3.14+/ 1.25)g/L, and those of PLT were (338+/-130)*10(9)/L and (229+/-129)*10(9)/L, respectively(P<0.05 for all). The positive rate of CTC was significantly higher in the metastasis group (82.8%), significantly higher than that in the non metastatic group (42.0%, P<0.001). The levels of D-D, FIB and PLT in the metastasis group were (2.33+/-1.95)mg/L, (4.13+/-1.43)g/L and (433+/-74)*10(9)/L, but were (1.40+/-2.03) mg/L, (3.15+/-1.37)g/L and (206+/-88)*10(9)/L in the non metastatic group (P<0.05 for all). CONCLUSIONS: The detection of circulating tumor cells may facilitate early prediction of distant metastasis of lung cancer. The hypercoagulation state is more-likely correlated with the distant metastasis of lung cancer. PMID- 27188608 TI - [Factors related to adjuvant ovarian function suppression in premenopausal breast cancer patients]. AB - OBJECTIVE: To analyze the applied condition of ovary function suppression (OFS) before and after joint analysis of TEXT and SOFT trials and SOFT trial, and to identify the relevant factors of OFS usage. METHODS: The analysis was performed in premenopausal women with hormone receptor (HR) positive breast cancer receiving surgical treatment from Apr 2013 to Oct 2015 in Ruijin Hospital, Shanghai Jiaotong University School of Medicine. Adjuvant treatment strategy was made in the multidisciplinary team (MDT) meetings. We analyzed the applied condition of OFS before and after joint analysis, SOFT trial and its relevant factors. RESULTS: Among 454 patients, 114 (25.1%) patients received OFS. Before the results of joint analysis came out, all the patients (38/38) received OFS together with tamoxifen (TAM); after the results came out, clinicians began to put OFS with exemestane into practice, among 76 patients, 41(53.9%) patients received OFS with exemestane while 35 (46.1%) patients received OFS together with TAM. Before the results of SOFT trial came out, 71 out of 310 (22.9%) patients received OFS while 43 out of 144 (29.9%) patients received OFS after that. No significant difference was found between the proportion of patients receiving OFS before and after the results of SOFT trial came out (P=0.112). Age, histological grade, pN status, Ki-67 status, molecular subtype and acceptance of chemotherapy were correlated with OFS treatment (P<0.05). Age, tumor grade and pN were independent significant predictors of OFS usage. CONCLUSIONS: After the results of joint analysis came out, clinicians began to apply OFS with exemestane to premenopausal women with HR positive breast cancer. There is no significant difference between the proportion of patients receiving OFS before and after SOFT trial. Age, tumor grade and pN status are independent significant predictors of OFS treatment. Patients younger than 40, with histological grade II or III tumor and with pN1 or pN2 status are prone to receive OFS. PMID- 27188609 TI - [Expression and intratumoral heterogeneity of LN-5gamma2 in esophageal squamous cell carcinoma]. AB - OBJECTIVE: The present study aimed to evaluate the expression and intratumoral heterogeneity of LN-5gamma2 in esophageal squamous cell carcinoma (ESCC). METHODS: The expression of LN-5gamma2 protein was examined in 135 ESCC cases by immunohistochemistry, and to analyze its relationship with the clinical relevance of patients. The protein expressions in different regions in the same tumor as well as different nests in the same region were compared. RESULTS: Moderate and high expression of LN-5gamma2 protein was detected in 40.0% (54/135) of tumor tissues. Positive immunohistochemical staining was observed in 31.1% (23/74) of early stage (stages I/II) cases and 50.8% (31/61) of late stage (stage III) cases, with a significant difference between these two groups (P=0.023). There was no statistical association of LN-5gamma2 expression with age, sex of patients, PT sage, lymph node metastasis and degree of tumor differentiation (P>0.05). However, differential expression of LN-5gamma2 protein was found at different sampling sites in the same tumor and the same sampling site in different carcinomas. CONCLUSION: High expression of LN-5gamma2 is positively correlated with tumor clinical stages and there existed intratumoral heterogeneity of LN-5gamma2 expression in ESCC tissues. PMID- 27188612 TI - [Prognostic analysis of gastrointestinal stromal tumors complicated with gastrointestinal bleeding]. AB - OBJECTIVE: To study the relationship between clinicopathological characteristics, prognosis and gastrointestinal bleeding in primary gastrointestinal stromal tumors (GIST). METHODS: The clinicopathological and follow-up data of 200 patients with gastrointestinal stromal tumors treated in our hospital from April 2008 to December 2014 were retrospectively reviewed. The correlation of gastrointestinal bleeding with gastrointestinal stromal tumor clinicopathological characteristics and prognosis were analyzed. RESULTS: The 200 GIST patients were divided into two groups according to the bleeding in the digestive tract, including 57 gastrointestinal bleeding patients and 143 non-bleeding patients. The mean tumor diameter was 6.5 cm (range 1.8-22 cm) in the bleeding group and 2.5 cm (range 0.4-18 cm) in the non-bleeding group (P<0.05). Of the 57 bleeding patients, 31 located in the stomach, 25 in the small intestine, and one had colorectal bleeding. Fifty patients had mitotic index (MI) <= 5/50 HPF, other 6 patients ranged between 5 and 10/50 HPF and one patient had MI >10/50 HPF. Six GIST patients were complicated with tumor rapture. But in the non-bleeding group, 125 patients had gastric GIST, 8 in the small intestine, one colorectum, and 9 had esophageal or other GIST. 141 patients had MI <=5/50 HPF, 1 patients ranged between 5 and 10/50 HPF and one patient had MI >10/50 HPF. Only 1 GIST patients was complicated with tumor rapture. The gastrointestinal bleeding was closely associated with tumor size, mitotic index, tumor location, risk classifications, tumor rapture and tumor recurrence (P<0.05 for all). The 3-year and 5-year survival rates of the 200 patients were 96.5% and 86.8%, respectively. 16 patients developed recurrence or metastasis, and 11 died of GIST. The 5-year survival rate of patients with gastrointestinal bleeding was 76.2%, significantly lower than that of patients without gastrointestinal bleeding (91.6%, P<0.05). CONCLUSIONS: GIST patients complicated with gastrointestinal bleeding have poor prognosis, and attention should be paid to stratifying patients for therapy. PMID- 27188613 TI - [Clinical analysis of liver transplantation in treatment of liver metastatic cancer]. AB - OBJECTIVE: To evaluate the feasibility and outcome of liver transplantation in the treatment of liver metastatic cancer. METHODS: Four patients with pathologically confirmed liver metastatic cancer underwent liver transplantation, including one of liver metastases from pancreatic endocrine tumor, one from rectal endocrine tumor, one from stomach stromal tumor and one from colorectal carcinoma. Classic surgical method was adopted, i. e. orthotopic liver transplantation for the recipients and transplants came from cadaveric donors. RESULTS: All the four patients had a smooth operation, an uneventful early postoperative recovery and good living quality. The patient with liver metastases from pancreatic endocrine tumor had liver tumor recurrence at four and a half years after the transplantation, and then underwent left lateral hepatic lobectomy, without any recurrence until now. The patient with liver metastases from rectal endocrine tumor had right renal and pelvic tumor metastasis at 16 months after the operation, and died of tumor recurrence 5 years after the liver transplantation. The patient with liver metastases from gastric stromal tumor had extensive pelvic metastases at five and a half months after the transplantation, and survived with tumor for 4 years and 6 months after the operation. The patient with liver metastases from colorectal carcinoma had extensive bilateral lung metastases at 3 months after the transplantation and died one and a half years after the operation. CONCLUSION: For well-differentiated unresectable metastatic liver cancers, liver transplantation may serve as a treatment option and better treatment results can be achieved for some highly selected patients. PMID- 27188578 TI - Calcific aortic stenosis. AB - Calcific aortic stenosis (AS) is the most prevalent heart valve disorder in developed countries. It is characterized by progressive fibro-calcific remodelling and thickening of the aortic valve leaflets that, over years, evolve to cause severe obstruction to cardiac outflow. In developed countries, AS is the third-most frequent cardiovascular disease after coronary artery disease and systemic arterial hypertension, with a prevalence of 0.4% in the general population and 1.7% in the population >65 years old. Congenital abnormality (bicuspid valve) and older age are powerful risk factors for calcific AS. Metabolic syndrome and an elevated plasma level of lipoprotein(a) have also been associated with increased risk of calcific AS. The pathobiology of calcific AS is complex and involves genetic factors, lipoprotein deposition and oxidation, chronic inflammation, osteoblastic transition of cardiac valve interstitial cells and active leaflet calcification. Although no pharmacotherapy has proved to be effective in reducing the progression of AS, promising therapeutic targets include lipoprotein(a), the renin-angiotensin system, receptor activator of NF kappaB ligand (RANKL; also known as TNFSF11) and ectonucleotidases. Currently, aortic valve replacement (AVR) remains the only effective treatment for severe AS. The diagnosis and staging of AS are based on the assessment of stenosis severity and left ventricular systolic function by Doppler echocardiography, and the presence of symptoms. The introduction of transcatheter AVR in the past decade has been a transformative therapeutic innovation for patients at high or prohibitive risk for surgical valve replacement, and this new technology might extend to lower-risk patients in the near future. PMID- 27188615 TI - [Multi-disciplinary treatment increases the survival rate of late stage pharyngeal, laryngeal or cervical esophageal cancers treated by free jejunal flap reconstruction after cancer resection]. AB - OBJECTIVE: To investigate the survival status of patients with pharyngeal, laryngeal or cervical esophageal cancers, who received free jejunal flap (FJF) to repair the defects following tumor resection, and to analyze the effect of multi disciplinary treatment on their survival. METHODS: Fifty-eight patients with pharyngeal, laryngeal or cervical esophageal cancer underwent free jejunal flap (FJF) reconstruction after cancer resection between 2010 and 2013. All their clinical records were reviewed and analyzed. RESULTS: The success rate of flap transplantation was 91.4% (53/58). The 2-year overall survival rates (OSR) of cervical esophageal cancer and hypopharyngeal cancer patients were 67.5% and 49.3%, respectively, both were significantly better than that of laryngeal cancer. The main causes of death were local recurrence and distant metastases. The group with no short-term complications had a better two-year OSR (59.0%) than the group with short-term complications (46.6%), however, the difference between them was not significant (P=0.103). The 2-year survival rate of the initial treatment group was 65.0%, better than that of the salvage treatment group (49.4%), but the difference was not significant (P=0.051). For the stage III and IV patients, the multi-disciplinary treatment group had a significantly better 2 year OSR (64.7%) than the single or sequential treatment group (37.0%, P=0.016). CONCLUSIONS: Free jejunal flap reconstruction is an ideal option for repairing the cervical digestive tract circumferential defects caused by tumor resection with a high success rate and a low mortality. Compared with the single or sequential treatment, multi-disciplinary treatment can significantly improve the survival rate of late-stage hypopharyngeal and cervical esophageal cancer patients. PMID- 27188616 TI - [Analysis of the diagnosis and treatment for six patients with gammadelta T-cell lymphoma or leukemia]. PMID- 27188611 TI - [Laparoscopic versus open wedge resection of gastric gastrointestinal stromal tumors: a non-randomized case-matched study]. AB - OBJECTIVE: To investigate the safety and feasibility of laparoscopic wedge resection for gastric gastrointestinal stromal tumors (GIST). METHODS: One hundred GIST patients treated in our department between 2010 and 2014 were retrospectively enrolled, and their clinicopathological data were reviewed. Fifty patients underwent laparoscopic wedge resection, and open surgery cases were 1?1 matched by tumor diameter. The clinicopathological characteristics, perioperative related factors, postoperative nutritional status and short-term outcome were compared between the two groups. RESULTS: Among the clinicopathological characteristics, only the age was of statistical significance (61.58+/-10.43 vs. 56.40+/-9.82, P=0.012). Over fifty percent of the tumors occurred in the gastric body. Although the short-term survival did not show statistical significance, the laparoscopic group showed predominant advantages in estimated blood loss [(48.60+/-48.89) ml vs. (137.60+/-140.69) ml, P<0.001], average hospital stay[ (12.14+/-4.32) d vs.(17.22+/-7.11) d, P<0.001], oral intake time[ (3.76+/-1.73)d vs. (6.28+/-3.73)d, P<0.01], decline of prealbumin [(0.07+/-0.04)g/L vs. (0.11+/ 0.05)g/L, P<0.001)], decline of transferrin [(0.51+/-0.29)g/L vs. (0.64+/ 0.30)g/L, P=0.034]and complication (2.0% vs. 14.0%, P=0.027). CONCLUSION: Laparoscopic wedge resection is feasible and safe for GIST surgery, allows a rapid recovery and having a better nutritional status in patients, and is a less invasive approach for patients. PMID- 27188614 TI - [Application of three-dimensional ultrasonography to assess the abdominal lymph node metastasis of gastric carcinoma]. AB - OBJECTIVE: To investigate the clinical value of three-dimensional ultrasonography (3D-US) in the diagnosis of abdominal lymph node metastasis of gastric carcinoma. METHODS: A total of 95 patients with gastric cancer diagnosed by gastroscopy and confirmed by pathology after operation were examined by 3D-US preoperatively.The characteristics of gastric carcinoma was assessed using QLAB software. The tumor volume, lesion diameter and invasion depth of gastric cancer were measured. RESULTS: All of the 95 subjects were divided into two groups according to their lymph nodes status postoperatively: group N+ , 71 patients with lymph node metastasis; and group N0, 24 patients without lymph node metastasis.The quantitative 3D-US analysis and pathological results of these two groups were compared with each other. The tumor volume of group N+ was significantly higher than that of the group N0 [(26.02+/-6.87)cm(3) vs. (13.11+/-2.79)cm(3), P<0.05], the invasion depth was significantly deeper in the group N+ than in the group N0 [(1.57+/-0.29)cm VS (1.10+/-0.29)cm, P<0.05]. However, there was no significant difference of the lesion diameters between these two groups. Multivariate analysis showed that tumor volume and depth of invasion are independently correlated with lymph node metastasis. A cut-off value=16.8 cm(3) of the tumor volume for assessing the lymph node metastasis had a sensitivity of 90.1% and specificity of 95.8%, respectively, obtained by the area under the ROC curve. CONCLUSION: The tumor volume of gastric cancer can be obtained by 3D ultrasonography, and the tumor volume can be considered as a new potential index to evaluate the abdominal lymph node metastasis of gastric cancer before surgery. PMID- 27188618 TI - The experience of depression, anxiety, and mania among perinatal women. AB - We assessed differential item functioning (DIF) based on computerized adaptive testing (CAT) to examine how perinatal mood disorders differ from adult psychiatric disorders. The CAT-Mental Health (CAT-MH) was administered to 1614 adult psychiatric outpatients and 419 perinatal women with IRB approval. We examined individual item-level differences using logistic regression and overall score differences by scoring the perinatal data using the original bifactor model calibration based on the psychiatric sample data and a new bifactor model calibration based on the perinatal data and computing their correlation. To examine convergent validity, we computed correlations of the CAT-MH with contemporaneously administered Edinburgh Postnatal Depression Scales (EPDS). The rate of major depression in the perinatal sample was 13 %. Rates of anxiety, mania, and suicide risk were 5, 6, and 0.4 %, respectively. One of 66 depression items, one of 69 anxiety items, and 15 of 53 mania items exhibited DIF (i.e., failure to discriminate between high and low levels of the disorder) in the perinatal sample based on the psychiatric sample calibration. Removal of these items resulted in correlations of the original and perinatal calibrations of r = 0.983 for depression, r = 0.986 for anxiety, and r = 0.932 for mania. The 91.3 % of cases were concordantly categorized as either "at-risk" or "low-risk" between the EPDS and the perinatal calibration of the CAT-MH. There was little evidence of DIF for depression and anxiety symptoms in perinatal women. This was not true for mania. Now calibrated for perinatal women, the CAT-MH can be evaluated for longitudinal symptom monitoring. PMID- 27188617 TI - [Insights on colorectal carcinoma based on the biological differences between left-sided and right- sided colon cancers]. AB - Previous studies have demonstrated that there are biological differences between colon and rectal cancers. Recently, some authors have proposed that colorectal cancer could be classified into several categories according to the primary sites of the tumor, proximal or distal. It is speculated that the differences are due to different embryologic origin and time to initial diagnosis. Further evidence supports that the molecular differences in the status of K-ras, BRAF, and microsatellite instability (MSI) based on primary sites in the bowel are the basis that impacts the response to therapeutic agents and patient prognosis. PMID- 27188621 TI - [Food intolerances caused by enzyme defects and carbohydrate malassimiliations : Lactose intolerance and Co]. AB - Apart from allergic conditions, carbohydrate malassimiliations (sugar metabolism disorders) are classified within the group of food intolerances. These dose dependent, yet non-immunological reactions require gastroenterological or internal diagnosis following nutritional therapy. Intolerances to carbohydrates such as lactose (milk sugar) and fructose (fruit sugar) in addition to sugar alcohols (sorbitol, mannitol, lactitol etc.) have been gaining increasing attention in recent decades as they are the cause of a wide range of gastrointestinal symptoms. There are currently various options for both diagnosis and therapy that differ notably in terms of effort, costs, and efficiency. Nutritional change and patient education are the bases of therapy. Non-observance of the trigger will result in increasing complaints and possibly even more infections, e.g., diverticula, rectal disorders, bacterial miscolonization, bile acid malabsorption). For an optimal therapy, the following sugar metabolism disorders have to be differentiated: hypolactasia versus lactose maldigestion, fructose malabsorption versus fructose overload, combined lactose and fructose intolerance, and isolated adverse reactions against sorbitol.For the medical conditions listed above, a three- or four-stage treatment regimen is recommended. Extensive dietary restrictions with regard to the relevant sugar, except for lactose, should not be maintained over a longer period of time. PMID- 27188622 TI - Dispersibility of vapor phase oxygen and nitrogen functionalized multi-walled carbon nanotubes in various organic solvents. AB - The synthesis and characterization of gas phase oxygen- and nitrogen functionalized multi-walled carbon nanotubes (OMWCNTs and NMWCNTs) and the dispersibility of these tubes in organic solvents were investigated. Recently, carbon nanotubes have shown supreme capacity to effectively enhance the efficiency of organic solar cells (OSCs). A critical challenge is to individualize tubes from their bundles in order to provide homogenous nano domains in the active layer of OSCs. OMWCNTs and NMWCNTs were synthesized via HNO3 vapor and NH3 treatments, respectively. Surface functional groups and the structure of the tubes were analyzed by temperature-programmed desorption, Fourier transform infrared spectroscopy, transmission electron microscopy, and Raman spectroscopy which confirmed the formation of functional groups on the tube surface and the enhancement of surface defects. Elemental analysis demonstrated that the oxygen and nitrogen content increased with increasing treatment time of the multi-walled carbon nanotube (MWCNT) in HNO3 vapor. According to ultra-violet visible spectroscopy, modification of the MWCNT increased the extinction coefficients of the tubes owing to enhanced compatibility of the functionalized tubes with organic matrices. PMID- 27188623 TI - Conjunctival flora of healthy and diseased eyes of grey seals (Halichoerus grypus): implications for treatment. AB - Ocular pathology is relatively common in stranded seals admitted to wildlife rehabilitation hospitals. Some have pre-existing problems, while others develop eye problems in captivity, and in particular ulcerative keratitis, due to factors such as large prominent eyes, suboptimal water quality, trauma and infighting. Despite treatment, corneal ulcerations can rapidly progress to 'melting' ulcers with subsequent rupture of the globe. In this case series, 32 grey seals (Halichoerus grypus) had conjunctival swabs taken on admission to a UK wildlife hospital to identify ocular bacterial flora and nine had subsequent swabs taken after four weeks to see if this changed in captivity. Additionally, nine seals with ocular pathology were also swabbed. Although a wide range of bacteria were cultured on admission, the most common isolates were Gemella haemolysans, Escherichia coli and Clostridium perfringens All 'melting' ulcers were associated with Pseudomonas aeruginosa, which suggests this bacterial species may be significant in the pathogenesis of progressive stromal ulceration in grey seals. PMID- 27188619 TI - Cases of human brucellosis in Sweden linked to Middle East and Africa. AB - BACKGROUND: Human brucellosis cases are still reported each year in Sweden despite eradication of the disease in animals. Epidemiological investigation has never been conducted to trace back the source of human infection in the country. The purpose of the study was to identify the source of infection for 16 human brucellosis cases that occurred in Sweden, during the period 2008-2012. RESULTS: The isolates were identified as Brucella melitensis and MLVA-16 genotyping revealed 14 different genotypes of East Mediterranean and Africa lineages. We also reported one case of laboratory-acquired brucellosis (LAB) that was shown to be epidemiological linked to one of the cases in the current study. CONCLUSIONS: Brucella melitensis was the only species diagnosed, confirming its highest zoonotic potential in the genus Brucella, and MLVA-16 results demonstrated that the cases of brucellosis in Sweden herein investigated, are imported and linked to travel in the Middle East and Africa. Due to its zoonotic concerns, any acute febrile illness linked to recent travel within those regions should be investigated for brucellosis and samples should be processed according to biosafety level 3 regulations. PMID- 27188620 TI - [Percutaneous coronary interventions : Use between 2004 and 2012 in Germany]. AB - BACKGROUND AND OBJECTIVE: Percutaneous coronary interventions (PCIs) are increasingly being performed in the treatment of coronary artery disease. The aim of this study is to describe the frequency of PCIs by age, sex, type, and setting of the intervention in Germany. METHODS: Based on routine data of more than eight million insurants from three statutory health insurance funds, quarterly sex- and age-specific intervention rates were calculated between 2004 and 2012. Moreover, inpatient PCIs were subdivided into PCIs with conventional bare metal stents (BMS) and PCIs with drug-eluting stents (DES). Rates were age- and sex standardized according to the age and sex distribution of the particular years in Germany. RESULTS: Standardized rates increased from 277.3 to 382.2 per 100,000 person-years between 2004 and 2012. The intervention rate was three times higher in men than in women. The relative increase in the overall rate and in the rate of PCI with DES during the study period were 38 and 548 % respectively, whereas the rate of PCI with BMS declined by 48 %. Of all PCIs, 7-11 % were outpatient PCIs during the study period. CONCLUSIONS: PCIs are increasingly being performed in Germany, particularly PCI with DES. The frequency of PCI with BMS implantation is decreasing. Sex-specific differences in the frequency of PCI go beyond differences that would have been expected because of a differing morbidity profile. Our analyses indicate that comparatively few outpatient PCIs are performed. PMID- 27188624 TI - Associations in the continuum of care for maternal, newborn and child health: a population-based study of 12 sub-Saharan Africa countries. AB - BACKGROUND: Despite the progress in the Millennium Development Goals (MDGs) 4 and 5, inequity in the utilization of maternal, newborn and child health (MNCH) care services still remain high in sub-Saharan Africa (SSA). The continuum of care for MNCH that recognizes a tight inter-relationship between maternal, newborn and child health at different time periods and location is key towards reducing inequity in health. In this study, we explored the distributions in the utilization MNCH services in 12 SSA countries and further investigated the associations in the continuum of care for MNCH. METHODS: Using Demographic and Health Surveys data of 12 countries in SSA, structural equation modeling approach was employed to analyze the complex relationships in continuum of care for MNCH model. The Full Information Maximum Likelihood estimation procedure which account for the Missing at Random (MAR) and Missing Completely at Random (MCAR) assumptions was adopted in LISREL 8.80. The distribution of MNCH care utilization was presented before the estimated association in the continuum of care for MNCH model. RESULTS: Some countries have a consistently low (Mali, Nigeria, DR Congo and Rwanda) or high (Namibia, Senegal, Gambia and Liberia) utilization in at least two levels of MNCH care. The path relationships in the continuum of care for MNCH from 'adequate antenatal care' to 'adequate delivery care' (0.32) and to 'adequate child's immunization' (0.36); from 'adequate delivery care' to 'adequate postnatal care' (0.78) and to 'adequate child's immunization' (0.15) were positively associated and statistically significant at p < 0.001. Only the path relationship from 'adequate postnatal care' to 'adequate child's immunization' (-0.02) was negatively associated and significant at p < 0.001. CONCLUSIONS: In conclusion, utilization of each level of MNCH care is related to the next level of care, that is - antenatal care is associated with delivery care which is then associated with postnatal and subsequently with child's immunization program. At the national level, identification of communities which are greatly contributing to overall disparity in health and a well laid out follow-up mechanism from pregnancy through to child's immunization program could serve towards improving maternal and infant health outcomes and equity. PMID- 27188625 TI - Comment on Fard et al.'s Candidate gene variants of the immune system and sudden infant death syndrome. PMID- 27188626 TI - Genetic polymorphisms of 26 Y-STR loci in the Mongolian minority from Horqin district, China. AB - To study the population data of Y chromosome STR (Y-STRs) of the Mongolian minority population residing in the Horqin district, we analyzed haplotypes of 26 Y-STRs (DYS19, DYS385a/b, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS481, DYS533, DYS549, DYS570, DYS576, DYS635, DYS643, DYS388, DYS449, DYS460, and YGATAH4) in 298 unrelated Chinese Mongolian individuals using the commercially available Goldeneye(r) DNA ID 26Y system. We also investigated blood stains, saliva spots, semen spots, hair follicles, fingernails, and sweat latent fingerprints from ten healthy males for testing the efficiency of direct amplification of this new Y-STRs system. The calculated average gene diversity values of the Mongolian population ranged from 0.3024 to 0.9510 for the DYS389I and DYS385a/b loci, respectively. The discriminatory capacity was 92.95 % with 277 observed haplotypes using 23 Y-STR loci (DYS19, DYS385a/b, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS481, DYS533, DYS549, DYS570, DYS576, DYS635, DYS643, and YGATAH4). By adding three more Y-STRs (DYS388, DYS449, and DYS460) to the 26Y system, the discriminatory capacity was increased to 94.63 % with a total of 282 observed haplotypes. Population relationships were calculated and compared with seven populations available from the Y chromosome haplotype reference database and data from ten Asian populations published previously. The Mongolian minority population residing in Horqin district is significantly different from other populations. Our results indicated that these 26 Y-STRs were highly genetically polymorphic in the Mongolian group and this contributes greatly to existing Chinese ethnic genetic information. As a result of direct amplification, we have obtained full profile from all blood stains, saliva spots, hair follicles, and fingernails; six semen spots; and one sweat latent fingerprint. It revealed that the 26 Y-STR system was a valuable tool for male sex analysis in forensic field and the kit was highly adaptive to direct amplification of various samples including blood stain, saliva spot, hair follicle, and fingernail. PMID- 27188628 TI - Erratum to: Is immunosenescence influenced by our lifetime "dose" of exercise? PMID- 27188627 TI - Co-effect of silk and amniotic membrane for tendon repair. AB - The objective of the present study was to determine the feasibility and biocompatibility of a silk scaffold and a composite silk scaffold in terms of new tendon generation using a rabbit Achilles tendon model. The silk scaffold was constructed using a weaving machine, then soaked in a 1% collagen-hyaluronan (HA) solution and air-dried, whereas the composite silk scaffold was composed of a silk scaffold containing a lyophilized collagen-HA substrate. Tenocytes were cultured in vitro to compare cell populations in the two groups. The cellular densities on composite silk scaffolds were 40% higher on average than those on silk scaffolds in 30-day tenocyte cultures. The tendon scaffolds had implanted into Achilles tendon defects in 16 white New Zealand rabbits. Rabbits were randomly divided into the following three groups: group I, silk scaffold alone; group II, composite silk scaffold; and group III, composite silk scaffold wrapped by an amniotic membrane. Implants were harvested 2, 8, and 12 weeks post implantation. Histological examinations were conducted using hematoxylin-eosin (H&E), Masson's trichrome, and by performing immunohistochemical staining for CD34. After 12 weeks, the three groups were distinguishable based on gross examination. The histological examination revealed more organized collagen fibrils in groups III, which showed a dense, parallel, linear organization of collagen bundles. CD34 staining revealed neoangiogenesis in groups III. The results of this research showed that collagen-HA substrates with amniotic membrane accelerate cellular migration and angiogenesis in neotendons. PMID- 27188629 TI - Biogenesis of antibiotics-viewing its history and glimpses of the future. AB - This review aims at comparing some historical data with the current situation in the study of biogenesis of natural compounds, antibiotics in the first place. Biogenesis of tetracyclines and cycloheximide and related compounds serves as example. Examples of molecular biological and bioinformatics methods used in the study of antibiotic biogenesis are described both in terms of its historical aspects and the current knowledge. PMID- 27188630 TI - Gender of the Clinician, Child, and Guardian and the Association With Receipt of Routine Adolescent Vaccines. AB - PURPOSE: To analyze the relationship of the gender of the clinician, child, and guardian to the child's receipt of human papilloma virus (HPV) vaccine, which prevents a sexually transmitted infection, compared to tetanus, diphtheria, acellular pertussis (Tdap) and meningococcal dose 1 (MCV4) vaccines, which do not. METHODS: We extracted electronic health record data from visits by adolescents 11-18 years of age to 27 primary care practices from 2009 to 2014. Visits with pediatricians, physician assistants, and nurse practitioners were included if they were the first at which HPV vaccine was due (n = 102,736). After stratifying by visit type (preventive/acute), generalized estimating equations with robust variance estimators accounted for clustering of visits within practices. Adjusting for all covariates, these models were used to estimate standardized proportions of "captured opportunities" (vaccine due and given) for HPV dose 1 (HPV), Tdap, and MCV4. RESULTS: Fewer opportunities were captured at acute versus preventive visits. Although rates were low, female clinicians delivered all three vaccines at higher rates than male clinicians at acute (HPV: 2.7% vs. 1.2%, p < .001; Tdap: 6.4% vs. 4.1%, p = .013; MCV4: 6.0% vs. 3.7%, p = .013) but not preventive visits. Girls received HPV vaccine at higher rates than boys early in the study period, but the gap closed over time (p < .001). Guardian gender was not associated with vaccination. CONCLUSIONS: Clinician gender was associated with vaccination at acute, but not preventive, visits. In the context of efforts to increase acute visit vaccination, differences between female and male clinicians' rates might reflect alternate practice styles by gender that deserve future study. PMID- 27188631 TI - Synthesis of isoalkanes over a core (Fe-Zn-Zr)-shell (zeolite) catalyst by CO2 hydrogenation. AB - A kind of core-shell catalyst with Fe-Zn-Zr as the core and a zeolite (HZSM-5, Hbeta, and HY) as the shell was synthesized by a simple cladding method. The catalyst has an obvious confinement effect on the synthesis of isoalkanes by CO2 hydrogenation. Especially, the Fe-Zn-Zr@HZSM-5-Hbeta catalyst with a double zeolite shell exhibits an extraordinary high i-HC/t-HC ratio. PMID- 27188633 TI - Semen characteristics and reaction time of Yankasa rams experimentally infected with Trypanosoma evansi infection. AB - Trypanosomosis is a serious, often fatal disease of domestic animals and humans, and a major constraint to livestock productivity and agricultural development in areas of Africa, Latin America, the Middle East, and Asia. It is caused by hemoflagelate protozoan of the genus Trypanosoma. Several species of Trypanosoma such as Trypanosoma congolense, Trypanosoma vivax, Trypanosoma brucei, and Trypanosoma evansi are known to infect domestic animals. Trypanosoma evansi is one of the most widespread pathogenic trypanosomes in the world causing disease known as "Surra" in animals. The effects of experimental T evansi infection on some aspects of reproduction in Yankasa rams were investigated over a 108-day period. Rams in the infected group A (n = 7) were each inoculated with 1 * 10(6) trypanosomes in 1 mL of donor blood via the jugular vein, whereas the control group B (n = 5) were administered 1 mL of normal saline. Semen volume, gross motility, live and/or dead sperm ratio, sperm morphologic abnormalities, and concentration as well as reaction time of infected and control rams were evaluated on a weekly basis. The results showed a nonsignificant (P > 0.05) decrease in semen volume and a significant (P < 0.05) decrease in concentration compared to the control rams. Reaction time showed considerable significant (P < 0.05) increase from preinfection values 26.7 +/- 4.54 to 94.7 +/- 7.54 seconds compared to control 32.9 +/- 2.64 to 33.4 +/- 4.78 seconds. Furthermore, semen gross motility for infected rams differed significantly (P < 0.05) from those of the control. There was a significant surge (P < 0.05) in the total sperm morphologic abnormalities in the infected rams to 90.75 +/- 2.73% by week 20 (14 weeks after infection), compared to preinfection value of 20.9 +/- 0.52%. The outcome of this study suggests that infection with T evansi in Yankasa rams has far reaching severe effects on their reproductive performance. PMID- 27188632 TI - Viruses and bacteria in Th2-biased allergic airway disease. AB - Allergic airway diseases are typically characterized by a type 2-biased inflammation. Multiple distinct viruses and bacteria have been detected in the airways. Recently, it has been confirmed that the microbiome of allergic individuals differs from that of healthy subjects, showing a close relationship with the type 2 response in allergic airway disease. In this review, we summarize the recent findings on the prevalence of viruses and bacteria in type 2-biased airway diseases and on the mechanisms employed by viruses and bacteria in propagating type 2 responses. The understanding of the microbial composition and postinfectious immune programming is critical for the reconstruction of the normal microflora and immune status in allergic airway diseases. PMID- 27188634 TI - Coassembly of Tobacco Mosaic Virus Coat Proteins into Nanotubes with Uniform Length and Improved Physical Stability. AB - Using tobacco mosaic virus coat proteins (TMVcp) from both sources of the plant and bacterial expression systems as building blocks, we demonstrate here a coassembly strategy of TMV nanotubes in the presence of RNA. Specifically, plant expressed cp (cpp) efficiently dominates the genomic RNA encapsidation to determine the length of assembled TMV nanotubes, whereas the incorporated Escherichia coli-expressed cp (cpec) improves the physical stability of TMV nanotubes by introducing disulfide bonds between the interfaces of subunits. We expect this coassembly strategy can be expanded to other virus nanomaterials to obtain desired properties based on rationally designed protein-RNA and protein protein interfacial interactions. PMID- 27188635 TI - Anger in psychological disorders: Prevalence, presentation, etiology and prognostic implications. AB - Anger is present as a key criterion in five diagnoses within DSM-5: Intermittent Explosive Disorder, Oppositional Defiant Disorder, Disruptive Mood Dysregulation Disorder, Borderline Personality Disorder and Bipolar Disorder. This review amasses scientific literature demonstrating that within each of these disorders, anger is a central clinical feature that is highly prevalent and predictive of important outcomes. For each disorder, we also discuss the phenomenology and etiology of anger. Although models of anger have been quite distinct across these disorders, few empirical studies have truly tested whether anger stems from different etiological factors across these different conditions. We end with a discussion of transdiagnostic research that draws from cognitive psychology, affective science, and the neuroscience of anger, and that also fits with integrative approaches to treatment. PMID- 27188636 TI - Bilateral Stereotactic Thalamotomy for Bilateral Musician's Hand Dystonia. AB - BACKGROUND: Focal hand dystonia in musicians, also known as musician's dystonia, is a task-specific movement disorder characterized by unwanted involuntary muscle contractions occurring only when playing a musical instrument. CASE DESCRIPTION: Case 1 was a 50-year-old female professional pianist who underwent staged bilateral ventro-oral (Vo) thalamotomy, with an interval between the first and second surgery of 4 years. The first surgery (right Vo thalamotomy) led to significant improvements in dystonic symptoms without any complications. Pre- and postoperative Tubiana's musician's dystonia scale (TMDS) scores were 2 and 5, respectively. The second surgery (left Vo thalamotomy) also led to significant improvements in dystonic symptoms, with dysarthria and verbal recall disturbance resolving within 3 months. Pre- and postoperative TMDS scores were 2 and 5, respectively. The patient was subsequently able to return to live-stage performances. Case 2 was a 48-year-old male clarinet repair technician who underwent staged bilateral Vo thalamotomy, with an interval between the first and second surgery of 13 months. The first surgery (right Vo thalamotomy) led to dramatic improvements in symptoms without any complications. Pre- and postoperative TMDS scores were 2 and 5, respectively. The second surgery (left Vo thalamotomy) also led to significant improvements in symptoms with transient hypophonia. Pre- and postoperative TMDS scores were 2 and 5, respectively. The patient was subsequently able to return to work without difficulty. CONCLUSIONS: The findings in these 2 cases indicate the utility of bilateral stereotactic Vo thalamotomy in the treatment of medically intractable musician's dystonia affecting both hands. PMID- 27188637 TI - Expanding the Horizon of the Suboccipital Retrosigmoid Approach to the Middle Incisural Space by Cutting the Tentorium Cerebelli: Anatomic Study and Illustration of 2 Cases. AB - OBJECTIVE: Complex skull base approaches are often used to treat lesions within the middle incisural space; yet the well-known retrosigmoid route may provide an effective avenue to this difficult-to-reach region. The purpose of this study was to quantify the exposure advantages on the middle incisural space provided by cutting of the tentorium cerebelli via a standard suboccipital retrosigmoid approach (i.e., via the cerebellopontine cistern route). Also, 2 illustrative cases are presented. METHODS: A suboccipital retrosigmoid approach to the middle incisural space was performed bilaterally in 3 specimens in the semisitting position. A quantitative analysis of the brainstem surface exposed above the origin of the trigeminal nerve was performed before and after tentorial incision. RESULTS: Tentorial cutting significantly improved the exposure of the middle incisural space cisternal structures such as the oculomotor and trochlear nerves and the superior cerebellar and posterior cerebral arteries. The mean brainstem surface exposed more than doubled (2.13-fold increase) after tentorial incision with an average increase from 73.18 mm(2) to 155.76 mm(2). When the endoscope was used, it was possible to follow the entire course of the cisternal, infratentorial trochlear nerve segment during the opening of the tentorial free edge, facilitating its preservation. In the illustrative cases, 2 cerebellopontine angle meningiomas with supratentorial and infratentorial extension were removed without any postoperative complication. CONCLUSIONS: Tentorial incision may be useful to extend the rostral exposure of the middle incisural space via a simple retrosigmoid approach, avoiding the need for more complex skull base routes. PMID- 27188639 TI - Application of 4-Dimensional Digital Subtraction Angiography for Dural Arteriovenous Fistulas. AB - BACKGROUND: Three-dimensional reconstruction of digital subtraction angiography (3D-DSA) is a useful imaging modality for assessing complex cerebrovascular lesions. However, due to the importance of flow over time in certain vascular lesions, 3D-DSA is of less value as it lacks the temporal resolution. Dural arteriovenous fistulas (AVFs) are complex lesions in which an arteriovenous shunt exists between meningeal arteries and a dural venous sinus or cortical vein. Traditional 2D-DSA, especially with superselective injections of feeding arteries, is currently the gold standard for assessment, but overlapping of opacified vessels can complicate interpretation. A novel imaging technique, 4D DSA, merges 3D reconstructions of multiple temporal series. It offers a unique perspective on complex cerebrovascular lesions and may offer several advantages in the assessment of dural AVF. METHODS: 4D-DSA images were acquired in 5 patients who presented with dural AVFs. All relevant clinical data, imaging, and procedural/operative reports were reviewed retrospectively. 4D-DSA images were reconstructed on a separate 3D workstation and compared to 2D and 3D-DSA images in an offline fashion. RESULTS: In all 5 cases, 4D-DSA proved to be useful in lesion assessment and treatment planning. This included observation (n = 2), microsurgery (n = 1), and endovascular embolization (n = 2). CONCLUSIONS: In the small series of patients in which it has been evaluated, 4D-DSA offers several advantages in assessing dural AVFs. The ability to see and manipulate feeding arteries in 3D combined with temporal resolution was useful in assessment and treatment planning. Continued experience with this imaging technique will be needed to identify its optimal use. PMID- 27188638 TI - Delayed Presentation of an Extracranial Internal Carotid Artery Pseudoaneurysm and Massive Epistaxis Secondary to a Nasal Foreign Body: Case Report and Review of the Literature. AB - BACKGROUND: Epistaxis is a very common medical condition and can often be controlled with conservative measures. Rarely, uncontrolled and life-threatening epistaxis can occur. CASE DESCRIPTION: We present the case of a 58-year-old man who developed delayed, massive epistaxis caused by an extracranial left internal carotid artery pseudoaneurysm caused by an intranasal foreign object without apparent recent trauma. The patient was successfully treated with endovascular stenting of the affected vessel segment. CONCLUSIONS: Massive epistaxis is a potentially lethal condition. Although the source uncommonly originates from the internal carotid artery, pseudoaneurysm rupture needs to be considered on the differential diagnosis in selected patients. This case illustrates the need for vigilance for the presence of foreign objects and/or vessel injuries in the setting of acute, massive epistaxis. Additionally, we describe treatment options and review the literature. PMID- 27188641 TI - My Crooked and Aching Neck-Surgical Management of Cervical Deformity. PMID- 27188640 TI - Neuroendoscopy in Kuwait: Evolution, Current Status, and Future Directions. AB - An overview of the development of neuroendoscopy at the neurosurgery department, Ibn Sina Hospital in Kuwait, is presented with an outline of difficulties and obstacles faced by the field until it reached its current status. The factors and solutions that helped us overcome these problems are also elaborated on. After a modest beginning few years ago, endoscopic skull base procedures, intraventricular neuroendoscopy, and spinal endoscopy are regularly performed in the department. Although neuroendoscopy is not per se a neurosurgical subspecialty, it is an area that requires special training. Achieving an appropriate level of care necessitates these highly trained neurosurgeons to collaborate together and with other specialties to create teamsgeared towards offering such treatment options topatients. Importantly, a multitude of essential facilities should be available to make such a pattern of practice possible. In our experience, this was made possible through continued efforts that have finally paid off and gradually led to a complete shift of the face of neuroendoscopic practice in our department. Our future endeavors aim at further development of neuroendoscopy in the department to create a center of excellence. PMID- 27188642 TI - Study of Changing Intracranial Venous Drainage Patterns in Petroclival Meningioma. AB - OBJECTIVE: To elucidate venous drainage patterns to avoid damage to the venous drainage route in the middle cranial fossa and superior petrosal sinus when employing the transpetrosal approach. METHODS: Venous drainage patterns were assessed using three-dimensional computed tomography venography in 22 hemispheres of petroclival meningioma (PCM) cases from patients who underwent primary surgery and 40 hemispheres of control cases. Intracranial venous drainage patterns were compared between control cases and PCM cases. RESULTS: The proportion of hemispheres with complete and medial superior petrosal sinus drainage patterns was lower in PCM cases. With regard to the superficial middle cerebral vein drainage pattern, the proportion of hemispheres with the cavernous sinus capture type was lower and the proportion with the emissary type was higher in PCM cases. The proportion of hemispheres with multiple greater anastomoses of the superficial middle cerebral vein was higher in PCM cases without the emissary type and cavernous sinus capture-type patterns. When the venous drainage route of the cavernous sinus capture type and/or emissary type was disturbed, in particular, greater anastomosis via the vein of Labbe and the vein of Trolard was needed to control venous drainage flow. CONCLUSIONS: In cases of venous drainage impairment secondary to PCM progression, the drainage route changed to the pterygoid plexus route through the emissary foramen and/or superior sagittal sinus and to the transverse sinus route through the greater anastomosis of the superficial middle cerebral vein. In the anterior transpetrosal approach, peeling off the dura propria of the trigeminal nerve of the foramen rotundum for petrous apex exposure may be associated with the potential risk of pterygoid plexus drainage route impairment. PMID- 27188643 TI - Proximal epithelioid sarcoma after a history of malignant melanoma: a diagnostic challenge. PMID- 27188644 TI - Hybrid systems based on "drug - in cyclodextrin - in nanoclays" for improving oxaprozin dissolution properties. AB - A combined approach based on drug complexation with cyclodextrins, and complex entrapment in nanoclays has been investigated, to join in a single delivery system the benefits of these carriers and potentiate their ability to improve the dissolution properties of oxaprozin (OXA), a poorly water-soluble anti inflammatory drug. Based on previous studies, randomly methylated beta cyclodextrin (RAMEB) was chosen as the most effective cyclodextrin for OXA complexation. Adsorption equilibrium studies performed on three different clays (sepiolite, attapulgite, bentonite) allowed selection of sepiolite (SV) for its greater adsorption power towards OXA. DSC and XRPD studies indicated drug amorphization in both binary OXA-RAMEB coground and OXA-SV cofused products, due to its complexation or very fine dispersion in the clay structure, respectively. The drug amorphous state was maintained also in the ternary OXA-RAMEB-SV cofused system. Dissolution studies evidenced a clear synergistic effect of RAMEB complexation and clay nanoencapsulation in improving the OXA dissolution properties, with an almost 100% increase in percent dissolved and dissolution efficiency compared to the OXA-RAMEB coground system. Therefore, the proposed combined approach represents an interesting tool for improving the therapeutic effectiveness of poorly soluble drugs, and reducing the CD amount necessary for obtaining the desired drug solubility and dissolution rate increase. PMID- 27188645 TI - Bioconjugated gold nanoparticles enhance cellular uptake: A proof of concept study for siRNA delivery in prostate cancer cells. AB - The chemistry of gold nanoparticles (AuNPs) facilitates surface modifications and thus these bioengineered NPs have been investigated as a means of delivering a variety of therapeutic cargos to treat cancer. In this study we have developed AuNPs conjugated with targeting ligands to enhance cell-specific uptake in prostate cancer cells, with a purpose of providing efficient non-viral gene delivery systems in the treatment of prostate cancer. As a consequence, two novel AuNPs were synthesised namely AuNPs-PEG-Tf (negatively charged AuNPs with the transferrin targeting ligands) and AuNPs-PEI-FA (positively charged AuNPs with the folate-receptor targeting ligands). Both bioconjugated AuNPs demonstrated low cytotoxicity in prostate cancer cells. The attachment of the targeting ligand Tf to AuNPs successfully achieved receptor-mediated cellular uptake in PC-3 cells, a prostate cancer cell line highly expressing Tf receptors. The AuNPs-PEI-FA effectively complexed small interfering RNA (siRNA) through electrostatic interaction. At the cellular level the AuNPs-PEI-FA specifically delivered siRNA into LNCaP cells, a prostate cancer cell line overexpressing prostate specific membrane antigen (PSMA, exhibits a hydrolase enzymic activity with a folate substrate). Following endolysosomal escape the AuNPs-PEI-FA.siRNA formulation produced enhanced endogenous gene silencing compared to the non-targeted formulation. Our results suggest both formulations have potential as non-viral gene delivery vectors in the treatment of prostate cancer. PMID- 27188646 TI - Hepatotoxicity evaluation of dextran stabilized iron oxide nanoparticles in Wistar rats. AB - Cellular and organ responses to nanoparticles are relevant in the context of use of nanoparticles for biomedical applications. The purpose of the present study was to determine the potential of dextran stabilized iron oxide nanoparticles (DIONPs) to influence hepatic uptake and consequently induce hepatotoxic response in rats following intravenous administration. Inductively coupled plasma atomic emission spectroscopy analysis revealed that DIONPs are rapidly taken up into the liver, progressively broken down to iron constituents and exported into blood, with a part of it being retained in the liver. The potential of DIONPs to induce oxidative stress response was determined by evaluating the time-dependent redox defense status. Maximum alterations in antioxidant activities were observed to occur within a period of 7days. However, this effect was not followed by significant increase in lipid peroxidation or modulation of hepatic enzymes such as alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase and bilirubin levels. Overall, these data imply that the liver retains functional integrity with a dose of 10mg/kg DIONPs, although with brief activation of redox defenses. PMID- 27188647 TI - F8-SIP mediated targeted photodynamic therapy leads to microvascular dysfunction and reduced glioma growth. AB - The extra domain A (ED A) of fibronectin has been identified as a tumor vessel specific neovascular marker in glioma. Antibody based vascular targeting against ED A of fibronectin allows precise accumulation of photosensitizer in glioma microvasculature and thereby promises to overcome drawbacks of current photodynamic therapy (PDT) for glioma treatment. Our aim was to characterize microcirculatory consequences of F8-small immunoprotein (SIP) mediated PDT by intravital microscopy (IVM) and to analyze the effects on glioma growth. For IVM SF126 glioma cells were implanted into dorsal skinfold-chamber of nude mice. PDT was performed after intravenous injection of photosensitizer (PS)-coupled F8-SIP or PBS (n = 4). IVM was performed before and after PDT for 4 days. Analysis included total and functional (TVD, FVD) vessel densities, perfusion index (PI), microvascular permeability and blood flow rate (Q). To assess tumor growth SF126 glioma cells were implanted subcutaneously. PDT was performed as a single and repetitive treatment after PS-F8-SIP injection (n = 5). Subcutaneous tumors were treated after uncoupled F8-SIP injection as control group (n = 5). PDT induced microvascular stasis and thrombosis with reduced FVD (24 h: 115.98 +/- 0.7 vs. 200.8 +/- 61.9 cm/cm(2)) and PI (39 +/- 11 vs. 70 +/- 10 %), whereas TVD was not altered (298 +/- 39.2 vs. 278.2 +/- 51 cm/cm(2)). Microvascular dysfunction recovered 4 days after treatment. Microvascular dysfunction led to a temporary reduction of glioma growth in the first 48 h after treatment with complete recovery 5 days after treatment. Repetitive PDT resulted in sustained reduction of tumor growth. F8-SIP mediated PDT leads to microvascular dysfunction and reduced glioma growth in a preclinical glioma model with recovery of microcirculation 4 days after treatment. Repetitive application of PDT overcomes microvascular recovery and leads to prolonged antiglioma effects. PMID- 27188648 TI - Single-incision totally extraperitoneal inguinal hernia repair is safe and feasible in elderly patients: A single-center experience of 365 procedures. AB - The aim of this study was to evaluate the feasibility and safety of SILS for totally extraperitoneal inguinal hernia repair in elderly patients. A retrospective analysis of 365 patients who underwent of SILS for totally extraperitoneal inguinal hernia repair from January 2012 to November 2015 at Osaka Police Hospital was performed, and the outcomes of patients aged <80 years and those aged >=80 years were compared. There was a greater proportion of patients with an ASA score >=3 among those >=80 years than among those <80 years. The mean operative time for unilateral inguinal hernia was 94 min in patients <80 years and 98 min in patients >=80 years. The mean operative time for bilateral inguinal hernia was 133 min in patients <80 years and 130 min in patients >=80. Intraoperative bleeding was minimal in all patients. Conversion to a different operative procedure occurred in 3% (10/322) of patients <80 years and in 5% (2/43) of patients >=80 years (P = 0.6). The mean postoperative hospital stay was 2.2 days for patients <80 years and 2.2 days for patients >=80 years. The mean follow-up period 21 +/- 14 months (range, 3-50 months) for patients <80 years and 17 +/- 14 months (range, 3-50 months) for patients >=80 years (P = 0.3). Postoperative complications were seen in 12% (38/322) of patients <80 years and in 14% (6/43) of patients >=80 years (P = 0.7). A seroma was seen in 9% (28/322) of patients <80 years and in 12% (5/43) of patients >=80 years (P = 0.6). A wound infection occurred in 2% (8/322) of patients <80 years. These seromas and wound infections were managed conservatively. Pulmonary embolism was seen in one patient <80 years (0.3%). There was no mortality or recurrence in either group. SILS for totally extraperitoneal inguinal hernia repair has good cosmesis and can be performed in elderly patients with acceptable morbidity and mortality. PMID- 27188651 TI - The McGurk effect: An investigation of attentional capacity employing response times. AB - This paper proposes a novel approach to assess audiovisual integration for both congruent and incongruent speech stimuli using reaction times (RT). The experiments are based on the McGurk effect, in which a listener is presented with incongruent audiovisual speech signals. A typical example involves the auditory consonant/b/combined with a visually articulated/g/, often yielding a perception of/d/. We quantify the amount of integration relative to the predictions of a parallel independent model as a function of attention and congruency between auditory and visual signals. We assessed RT distributions for congruent and incongruent auditory and visual signals in a within-subjects signal detection paradigm under conditions of divided versus focused attention. Results showed that listeners often received only minimal benefit from congruent auditory visual stimuli, even when such information could have improved performance. Incongruent stimuli adversely affected performance in divided and focused attention conditions. Our findings support a parallel model of auditory-visual integration with interactions between auditory and visual channels. PMID- 27188649 TI - Long-Term Follow-Up of a Phase II Trial of Six Cycles of Dose-Dense R-CHOP-14 for First-Line Treatment of Diffuse Large B-Cell Lymphoma in Young and Elderly Patients. AB - BACKGROUND/AIMS: Rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) every 14 days seems to achieve better outcomes than R-CHOP every 21 days in diffuse large B-cell lymphoma (DLBCL) patients. Currently, the standard regimen is R-CHOP every 21 days. METHODS: This is a phase II clinical trial of treatment with 6 cycles of R-CHOP-14 with pegfilgrastim support in 2 populations of previously untreated DLBCL patients aged >=65 years (n = 73) or <65 years (n = 51) with low-risk International Prognostic Index scores (0-2). RESULTS: With a median follow-up of 63.7 months, the 5-year event-free survival rate was 53.8% in patients aged >=65 years and 71.0% in patients aged <65 years. The 5-year overall survival rate was 71.4 and 89.8%, respectively. The complete remission rate was 69.9% for older and 80.4% for younger patients. The median relative dose intensity of cytotoxic drugs was 143.2% in the elderly and 149.1% in the young patients. Febrile neutropenia was the most common grade 3-4 adverse event, being higher in elderly patients (21.3 vs. 9.3%). Eight deaths (7 in elderly patients) were considered treatment related. CONCLUSION: In conclusion, the R-CHOP-14 regimen is feasible and very active, though it is more toxic in elderly patients mainly due to an increased incidence of infections. New strategies, such as new monoclonal antibodies or new targeted therapies, are needed to improve the outcomes of DLBCL patients. PMID- 27188653 TI - Selective attention modulates the effect of target location probability on redundant signal processing. AB - We investigated the decision process underlying the detection of targets at multiple locations. In three experiments using the same observers, target location probability and attentional instructions were manipulated. A redundant target detection task was conducted in which participants were required to detect a dot presented at one of two locations. When the dot appeared at the two locations with equal frequency (Experiment 1), those participants who were found to have limited to unlimited capacity were shown to adopt a parallel, self terminating strategy. By contrast, those participants who had supercapacity were shown to process redundant targets in a coactive manner. When targets were presented with unequal probability, two participants adopted a parallel, self terminating strategy regardless of whether they were informed the target location probability (Experiment 3) or not (Experiment 2). For the remaining two participants, the strategy changed from parallel, self-terminating to serial, self-terminating as a result of the probability instructions. In Experiments 2 and 3, all the participants were of unlimited to limited capacity. Taken together, these results suggest that target location probability differently affects the selection of a decision strategy and highlight the role of controlled attention in selecting a decision strategy. PMID- 27188652 TI - Choosing attentional control settings in a dynamically changing environment. AB - Goal-directed attentional control supports efficient visual search by prioritizing relevant stimuli in the environment. Previous research has shown that goal-directed control can be configured in many ways, and often multiple control settings can be used to achieve the same goal. However, little is known about how control settings are selected. We explored the extent to which the configuration of goal-directed control is driven by performance maximization (optimally configuring settings to maximize speed and accuracy) and effort minimization (selecting the least effortful settings). We used a new paradigm, adaptive choice visual search, which allows participants to choose one of two available targets (a red or a blue square) on each trial. Distractor colors vary predictively across trials, such that the optimal target switches back and forth throughout the experiment. Results (N = 43) show that participants chose the optimal target most often, updating to the new target when the environment changed, supporting performance maximization. However, individuals were sluggish to update to the optimal color, consistent with effort minimization. Additionally, we found a surprisingly high rate of nonoptimal choices and switching between targets, which could not be explained by either factor. Analysis of participants' self-reported search strategy revealed substantial individual differences in the control strategies used. In sum, the adaptive choice visual search enables a fresh approach to studying goal-directed control. The results contribute new evidence that control is partly determined by both performance maximization and effort minimization, as well as at least one additional factor, which we speculate to include novelty seeking. PMID- 27188654 TI - Transplantation of human amniotic mesenchymal stem cells promotes neurological recovery in an intracerebral hemorrhage rat model. AB - Human amniotic membrane mesenchymal stem cells (hAMSCs) have recently been suggested as ideal candidate stem cells for cell-based therapy. Many studies have reported the therapeutic effects of hAMSCs in numerous disease models. However, no studies have used hAMSCs to treat intracerebral hemorrhage (ICH). In the present study, we examined the therapeutic potential of hAMSCs in a rat model of ICH, and characterized the possible mechanisms of action. Adult male Wistar rats were subjected to ICH by intrastriatal injection of VII collagenase, and then were intracerebrally administered hAMSCs, fibroblasts, or phosphate-buffered saline (PBS) at 24 h after ICH. Compared with the fibroblasts and the PBS control, hAMSCs treatment significantly promoted neurological recovery, and reduced the numbers of ED1(+) activated microglia, as well as myeloperoxidase (MPO(+)), and caspase-3(+) cells in the brain injury model. In addition, hAMSCs treatment significantly increased the expression of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) in the injured brain, and promoted neurogenesis and angiogenesis, compared with the fibroblasts and the PBS control. The transplanted hAMSCs survived for at least 27 days and were negative for beta-tubulin III and glial fibrillary acidic protein (GFAP). Taken together, the results suggest that hAMSCs treatment significantly promotes neurological recovery in rats after ICH. The mechanism of action could be mediated by inhibition of inflammation and apoptosis, increasing neurotrophic factor expression, and promotion of neurogenesis and angiogenesis. Thus, hAMSCs are candidate stem cells for the treatment of ICH. PMID- 27188655 TI - Louse-borne relapsing fever - report of four cases in Switzerland, June-December 2015. AB - BACKGROUND: Louse-borne relapsing fever (LBRF) is a neglected disease that has been restricted to East Africa for many decades. Several cases in refugees from the Horn of Africa have been recently diagnosed in four European countries. CASE PRESENTATION: We report four additional cases of LBRF in asylum seekers from Somalia and Eritrea who presented with fever shortly after arriving in Switzerland during a seven-month period. Multiple spirochetes were visualized on stained blood films which were identified as Borrelia recurrentis by 16S rRNA gene sequencing. All patients recovered after antibiotic treatment with ceftriaxone and/or doxycycline. Concurrent infections (malaria and tuberculosis) were diagnosed in half of our patients. Possible modes of transmission and preventive measures are discussed. CONCLUSIONS: These reported cases highlight the ongoing transmission of LBRF in migrants from East Africa. Diagnosis of LBRF cases and prevention of autochthonous transmission in asylum seeker camps are important steps for the near future. PMID- 27188657 TI - Leishmania major and Trypanosoma cruzi present distinct DNA damage responses. AB - Leishmania major and Trypanosoma cruzi are medically relevant parasites and interesting model organisms, as they present unique biological processes. Despite increasing data regarding the mechanisms of gene expression regulation, there is little information on how the DNA damage response (DDR) occurs in trypanosomatids. We found that L. major presented a higher radiosensitivity than T. cruzi. L. major showed G1 arrest and displayed high mortality in response to ionizing radiation as a result of the inefficient repair of double-strand breaks (DSBs). Conversely, T. cruzi exhibited arrest in the S/G2 cell cycle phase, was able to efficiently repair DSBs and did not display high rates of cell death after exposure to gamma irradiation. L. major showed higher resistance to alkylating DNA damage, and only L. major was able to promote DNA repair and growth recovery in the presence of MMS. ASF1c overexpression did not interfere with the efficiency of DNA repair in either of the parasites but did accentuate the DNA damage checkpoint response, thereby delaying cell fate after damage. The observed differences in the DNA damage responses of T. cruzi and L. major may originate from the distinct preferred routes of genetic plasticity of the two parasites, i.e., DNA recombination versus amplification. PMID- 27188658 TI - Characterization of nine microsatellite loci for Dicrocoelium dendriticum, an emerging liver fluke of ungulates in North America, and their use to detect clonemates and random mating. AB - This study characterizes polymorphic microsatellite loci from adults of the liver fluke Dicrocoelium dendriticum sampled from a population of sympatric beef cattle and wapiti in a region of emergence in southern Alberta, Canada. We also scrutinized the markers to validate their use in studying the population genetics of this complex life cycle parasite. Among the nine loci described, four deviated significantly from Hardy Weinberg Equilibrium (HWE) due to technical artefacts. The remaining five loci were in HWE. These five provided sufficient resolution to identify clonemates produced from the obligate asexual reproduction phase of the life cycle in snails and to assess the impact of non-random transmission of clonemates on measures of FIS, FST and genotypic disequilibrium. Excluding clonemates, we show that the sub-population of worms was in HWE, that average FIS within hosts was 0.003 (p=0.4922) and that there was no population genetic structure among hosts FST=0.001 (p=0.3243). These markers will be useful for studies of Dicrocoelium dendriticum ecology, transmission, and evolution. PMID- 27188659 TI - Menopause. AB - Menopause is an inevitable component of ageing and encompasses the loss of ovarian reproductive function, either occurring spontaneously or secondary to other conditions. It is not yet possible to accurately predict the onset of menopause, especially early menopause, to give women improved control of their fertility. The decline in ovarian oestrogen production at menopause can cause physical symptoms that may be debilitating, including hot flushes and night sweats, urogenital atrophy, sexual dysfunction, mood changes, bone loss, and metabolic changes that predispose to cardiovascular disease and diabetes. The individual experience of the menopause transition varies widely. Important influential factors include the age at which menopause occurs, personal health and wellbeing, and each woman's environment and culture. Management options range from lifestyle assessment and intervention through to hormonal and non-hormonal pharmacotherapy, each of which has specific benefits and risks. Decisions about therapy for perimenopausal and postmenopausal women depend on symptomatology, health status, immediate and long-term health risks, personal life expectations, and the availability and cost of therapies. More effective and safe therapies for the management of menopausal symptoms need to be developed, particularly for women who have absolute contraindications to hormone therapy. For an illustrated summary of this Primer, visit: http://go.nature.com/BjvJVX. PMID- 27188660 TI - Alcohol industry self-regulation: who is it really protecting? AB - Self-regulation has been promoted by the alcohol industry as a sufficient means of regulating alcohol marketing activities. However, evidence suggests that the guidelines of self-regulated alcohol marketing codes are violated routinely, resulting in excessive alcohol marketing exposure to youth and the use of content that is potentially harmful to youth and other vulnerable populations. If the alcohol industry does not adhere to its own regulations the purpose and design of these codes should be questioned. Indeed, implementation of alcohol marketing self-regulation in Brazil, the United Kingdom and the United States was likely to delay statutory regulation rather than to promote public health. Moreover, current self-regulation codes suffer from vague language that may allow the industry to circumvent the guidelines, loopholes that may obstruct the implementation of the codes, lax exposure guidelines that can allow excessive youth exposure, even if properly followed, and a standard of review that may be inappropriate for protecting vulnerable populations. Greater public health benefits may be realized if legislative restrictions were applied to alcohol marketing, and strict statutory alcohol marketing regulations have been implemented and defended successfully in the European Union, with European courts declaring that restrictions on alcohol marketing are proportional to the benefits to public health. In contrast, attempts to restrict alcohol marketing activities in the United States have occurred through private litigation and have been unsuccessful. None the less, repeated violations of industry codes may provide legislators with sufficient justification to pass new legislation and for such legislation to withstand constitutional review in the United States and elsewhere. PMID- 27188661 TI - Wall motion at 4D-CT angiography and surgical correlation in unruptured intracranial aneurysms: a pilot study. AB - BACKGROUND: Unruptured intracranial aneurysms (UIAs) are reported more frequently nowadays but their management is not well established; it depends on different structural features of the aneurysms and on multiple patient's risk factors. With this prospective observational study we report our preliminary experience by using four-dimensional (4D) computed tomographic (CT) angiography with ECG-gated reconstructions in the evaluation of dynamic modifications of the aneurysm wall, as a potential predicting factor of growth or rupture. The novelty of this study consists in correlation between Angio 4D-CT angiography images and surgical findings; only few scientific papers, in fact, have studied this issue. METHODS: Thirty-one patients (1 male, 30 females; 59.0+/-12.7 years old) with 43 unruptured aneurysms (medium size: 5.2+/-3.0 mm) were studied. ECG-triggered 4D CT angiography was performed with a 320-detector CT system (Aquilion ONE; Toshiba Medical Systems Corporation, Japan); ECG-gated reconstruction was performed for visualizing local displacement of the aneurysmal wall over a heart cycle. In the aneurysms surgically treated in our institution we were able to compare the macroscopic features of the aneurysm wall with 4D-CTA findings. We performed long term follow-up on untreated patients. RESULTS: Pulsation was detected in 13 of 43 unruptured aneurysms. Eighteen aneurysms were treated: thirteen were surgically treated and five underwent embolization with detachable coil placement. In nine aneurysms surgically treated in our institution (5 with pulsation and 4 without) we observed a significant correlation between 4D-CTA findings and macroscopic features of the aneurysms wall, in particular the pulsations detected at 4D-CTA study have shown to correspond to dark-reddish thinner wall at surgery. CONCLUSION: Our data confirm the previous reports concerning the reliability of 4D-CT angiography with ECG-gated reconstructions in defining the dynamic and structural features of the aneurysm wall. Moreover, optimal correlation rate between the findings provided by the 4D-CTA and the macroscopic surgical evaluation support a possible role of this technique to identify aneurysms with a higher risk of rupture. PMID- 27188662 TI - As2 O3 combined with leflunomide prolongs heart xenograft survival via suppressing the response of Th1, Th2, and B cells in a rat model. AB - Xenotransplantation remits the severe shortage of human organs and tissues for transplantation, which is a problem that severely limits the application of transplantation to the treatment of human disease. However, severe immune rejection significantly limits the efficacy of xenotransplantation. In this study, we systematically investigated the immunosuppressive effect and mechanism of action of As2 O3 and leflunomide using a hamster-to-rat heart xenotransplantation model. We initially examined heart xenograft survival following As2 O3 and leflunomide treatment alone or combined treatment. We found that treatment with As2 O3 combined with leflunomide can significantly prolong the survival of heart xenograft by inhibiting Th1 and Th2 differentiation and reducing the production of IgG and IgM. Interestingly, As2 O3 and leflunomide showed low toxicity to the organs of the recipient. Taken together, these observations indicate that treatment with As2 O3 combined with leflunomide may be a promising immunosuppressive schedule for xenotransplantation. PMID- 27188663 TI - An evaluation of the clinical and cost-effectiveness of alternative care locations for critically ill adult patients with acute traumatic brain injury. AB - BACKGROUND: For critically ill adult patients with acute traumatic brain injury (TBI), we assessed the clinical and cost-effectiveness of: (a) Management in dedicated neurocritical care units versus combined neuro/general critical care units within neuroscience centres. (b) 'Early' transfer to a neuroscience centre versus 'no or late' transfer for those who present at a non-neuroscience centre. METHODS: The Risk Adjustment In Neurocritical care (RAIN) Study included prospective admissions following acute TBI to 67 UK adult critical care units during 2009-11. Data were collected on baseline case-mix, mortality, resource use, and at six months, Glasgow Outcome Scale Extended (GOSE), and quality of life (QOL) (EuroQol 5D-3L). We report incremental effectiveness, costs and cost per Quality-Adjusted Life Year (QALY) of the alternative care locations, adjusting for baseline differences with validated risk prediction models. We tested the robustness of results in sensitivity analyses. FINDINGS: Dedicated neurocritical care unit patients (N = 1324) had similar six-month mortality, higher QOL (mean gain 0.048, 95% CI -0.002 to 0.099) and increased average costs compared with those managed in combined neuro/general units (N = 1341), with a lifetime cost per QALY gained of L14,000. 'Early' transfer to a neuroscience centre (N = 584) was associated with lower mortality (odds ratio 0.52, 0.34 0.80), higher QOL for survivors (mean gain 0.13, 0.032-0.225), but positive incremental costs (L15,001, L11,123 to L18,880) compared with 'late or no transfer' (N = 263). The lifetime cost per QALY gained for 'early' transfer was L11,000. CONCLUSIONS: For critically ill adult patients with acute TBI, within neuroscience centres management in dedicated neurocritical care units versus combined neuro/general units led to improved QoL and higher costs, on average, but these differences were not statistically significant. This study finds that 'early' transfer to a neuroscience centre is associated with reduced mortality, improvement in QOL and is cost-effective. PMID- 27188664 TI - A New Method for Preparing Mesenchymal Stem Cells and Labeling with Ferumoxytol for Cell Tracking by MRI. AB - Mesenchymal stem cells (MSCs) are among the major stem cells used for cell therapy and regenerative medicine. In-vivo cell-tracking by magnetic resonance imaging (MRI) is crucial for regenerative medicine, allowing verification that the transplanted cells reach the targeted sites. Cellular MRI combined with superparamagnetic iron-oxide (SPIO) contrast agents is an effective cell-tracking method. Here, we are reporting a new "bio-mimicry" method by making use of the "in-vivo environment" of MSCs to prepare native MSCs, so that (i) the phagocytic activity of cultured MSCs can be recovered and expanded MSCs can be ex-vivo labeled with Ferumoxytol, which is currently the only FDA approved SPIO nanoparticles for human use. Using our new method, 7-day cultured MSCs regain the capability to take up Ferumoxytol and exhibit an intracellular iron concentration of 2.50 +/- 0.50 pg/MSC, comparable to that obtained by using Ferumoxytol-heparin protamine nanocomplex; and (ii) cells can be re-sized to more native size, reducing from 32.0 +/- 7.2 MUm to 19.5 +/- 5.2 MUm. Our method can be very useful for expanding MSCs and labeling with Ferumoxytol, without the need for transfection agents and/or electroporation, allowing cell-tracking by MRI in both pre-clinical and clinical studies. PMID- 27188666 TI - Chronic Pain Types Differ in Their Reported Prevalence of Post -Traumatic Stress Disorder (PTSD) and There Is Consistent Evidence That Chronic Pain Is Associated with PTSD: An Evidence-Based Structured Systematic Review. AB - Objectives: The hypotheses of this systematic review were the following: 1) Prevalence of post-traumatic stress disorder (PTSD) will differ between various types of chronic pain (CP), and 2) there will be consistent evidence that CP is associated with PTSD. Methods: Of 477 studies, 40 fulfilled the inclusion/exclusion criteria of this review and were grouped according to the type of CP. The reported prevalence of PTSD for each grouping was determined by aggregating all the patients in all the studies in that group. Additionally all patients in all groupings were combined. Percentage of studies that had found an association between CP and PTSD was determined. The consistency of the evidence represented by the percentage of studies finding an association was rated according to the Agency for Health Care Policy and Research guidelines. Results: Grouping PTSD prevalence differed ranging from a low of 0.69% for chronic low back pain to a high of 50.1% in veterans. Prevalence in the general population with CP was 9.8%. Of 19 studies, 16 had found an association between CP and PTSD (84.2%) generating an A consistency rating (consistent multiple studies). Three of the groupings had an A or B (generally consistent) rating. The veterans grouping received a C (finding inconsistent) rating. Conclusion: The results of this systematic review confirmed the hypotheses of this review. PMID- 27188668 TI - Targeting PARP in Prostate Cancer: Novelty, Pitfalls, and Promise. AB - Metastatic prostate cancer remains a highly lethal disease with no curative therapeutic options. A significant subset of patients with prostate cancer harbor either germline or somatic mutations in DNA repair enzyme genes such as BRCA1, BRCA2, or ATM. Emerging data suggest that drugs that target poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) enzymes may represent a novel and effective means of treating tumors with these DNA repair defects, including prostate cancers. Here we will review the molecular mechanism of action of PARP inhibitors and discuss how they target tumor cells with faulty DNA repair functions and transcriptional controls. We will review emerging data for the utility of PARP inhibition in the management of metastatic prostate cancer. Finally, we will place PARP inhibitors within the framework of precision medicine based care of patients with prostate cancer. PMID- 27188669 TI - PARP Inhibition in Prostate Cancer: A Promising Approach. PMID- 27188667 TI - The composition of immune cells serves as a predictor of adaptive immunity in a cohort of 50- to 74-year-old adults. AB - Influenza causes significant morbidity and mortality annually. Although vaccination offers a considerable amount of protection, it is far from perfect, especially in aging populations. This is due to age-related defects in immune function, a process called immunosenescence. To date, there are no assays or methods to predict or explain variations in an individual's level of response to influenza vaccination. In this study, we measured levels of several immune cell subsets at baseline (Day 0) and at Days 3 and 28 post-vaccination using flow cytometry. Statistical modelling was performed to assess correlations between levels of cell subsets and Day 28 immune responses - haemagglutination inhibition (HAI) assay, virus neutralizing antibody (VNA) assay, and memory B cell ELISPOT. Changes in several groups of cell types from Day 0 to Day 28 and Day 3 to Day 28 were found to be significantly associated with immune response. Baseline levels of several immune cell subsets, including B cells and regulatory T cells, were able to partially explain variation in memory B-cell ELISPOT results. Increased expression of HLA-DR on plasmacytoid dendritic cells after vaccination was correlated with increased HAI and VNA responses. Our data suggest that the expression of activation markers (HLA-DR and CD86) on various immune cell subsets, as well as the relative distribution of cell subsets, both have value in predicting immune responses to influenza vaccination in older individuals. PMID- 27188670 TI - Using Medical Cannabis in an Oncology Practice. PMID- 27188671 TI - Applications of Genomic Sequencing in Pediatric CNS Tumors. AB - Recent advances in genome-scale sequencing methods have resulted in a significant increase in our understanding of the biology of human cancers. When applied to pediatric central nervous system (CNS) tumors, these remarkable technological breakthroughs have facilitated the molecular characterization of multiple tumor types, provided new insights into the genetic basis of these cancers, and prompted innovative strategies that are changing the management paradigm in pediatric neuro-oncology. Genomic tests have begun to affect medical decision making in a number of ways, from delineating histopathologically similar tumor types into distinct molecular subgroups that correlate with clinical characteristics, to guiding the addition of novel therapeutic agents for patients with high-risk or poor-prognosis tumors, or alternatively, reducing treatment intensity for those with a favorable prognosis. Genomic sequencing has also had a significant impact on translational research strategies in pediatric CNS tumors, resulting in wide-ranging applications that have the potential to direct the rational preclinical screening of novel therapeutic agents, shed light on tumor heterogeneity and evolution, and highlight differences (or similarities) between pediatric and adult CNS tumors. Finally, in addition to allowing the identification of somatic (tumor-specific) mutations, the analysis of patient matched constitutional (germline) DNA has facilitated the detection of pathogenic germline alterations in cancer genes in patients with CNS tumors, with critical implications for genetic counseling and tumor surveillance strategies for children with familial predisposition syndromes. As our understanding of the molecular landscape of pediatric CNS tumors continues to advance, innovative applications of genomic sequencing hold significant promise for further improving the care of children with these cancers. PMID- 27188672 TI - Pediatric Neuro-Oncology: Time to Go Molecular. PMID- 27188673 TI - Oncocytic Neoplasm on Renal Mass Biopsy: A Diagnostic Conundrum. PMID- 27188674 TI - The Role of Intralesional Therapies in Melanoma. AB - The US Food and Drug Administration has been rapidly approving new checkpoint inhibitors and targeted therapies for melanoma and other tumors. Recently, it approved the first intralesional therapy, talimogene laherparepvec (T-VEC), for the treatment of metastatic melanoma lesions in the skin and lymph nodes. Several other intralesional therapies (PV-10, interleukin-12 electroporation, coxsackievirus A21 [CVA21]) are entering later-stage testing. Locally injected agents have clearly shown their ability to produce local responses that can be durable. The possibility that they also stimulate a regional and even systemic immune response is exciting, as this potential effect may have utility in combination regimens; such regimens are an area of active research. Favorable responses with minimal toxicities in monotherapy trials have led to the first melanoma studies of T-VEC in combination with the cytotoxic T-lymphocyte associated antigen 4 inhibitor ipilimumab and, separately, with the programmed death 1-blocking antibody pembrolizumab. Studies of PV-10 with pembrolizumab and of CVA21 with pembrolizumab are also being initiated. Preliminary analyses of the results of the first combination trials, which show higher response rates than with either agent alone, offer some optimism that these locoregional therapies will find application--as treatment for patients who cannot tolerate systemic immunotherapies, to alleviate locoregional morbidity, and perhaps even to "prime" the immune system. PMID- 27188675 TI - A Review of Novel Intralesional Therapies for Melanoma, With an Emphasis on a Potential Combination Approach. PMID- 27188665 TI - Varicella zoster virus infection. AB - Infection with varicella zoster virus (VZV) causes varicella (chickenpox), which can be severe in immunocompromised individuals, infants and adults. Primary infection is followed by latency in ganglionic neurons. During this period, no virus particles are produced and no obvious neuronal damage occurs. Reactivation of the virus leads to virus replication, which causes zoster (shingles) in tissues innervated by the involved neurons, inflammation and cell death - a process that can lead to persistent radicular pain (postherpetic neuralgia). The pathogenesis of postherpetic neuralgia is unknown and it is difficult to treat. Furthermore, other zoster complications can develop, including myelitis, cranial nerve palsies, meningitis, stroke (vasculopathy), retinitis, and gastroenterological infections such as ulcers, pancreatitis and hepatitis. VZV is the only human herpesvirus for which highly effective vaccines are available. After varicella or vaccination, both wild-type and vaccine-type VZV establish latency, and long-term immunity to varicella develops. However, immunity does not protect against reactivation. Thus, two vaccines are used: one to prevent varicella and one to prevent zoster. In this Primer we discuss the pathogenesis, diagnosis, treatment, and prevention of VZV infections, with an emphasis on the molecular events that regulate these diseases. For an illustrated summary of this Primer, visit: http://go.nature.com/14xVI1. PMID- 27188676 TI - Management of Pregnant Patients With Cancer. PMID- 27188677 TI - Novel Combination Treatments in Multiple Myeloma. AB - The last decade has witnessed the identification of several novel druggable targets in multiple myeloma, leading to identification of novel therapies with clinically proven efficacy, both in the newly diagnosed and relapsed setting. More importantly, a common theme of good outcomes was observed among prospective randomized studies that have utilized combinations of agents with different mechanisms of action. The correlation between achieving a deeper response and the improvement in progression-free survival and overall survival has never been so clear. In this article, we elucidate the rationale for use of novel drug combinations in patients with myeloma, and review current evidence-based data supporting the use of specific combinations in various settings. We also attempt to craft a framework to guide clinicians in optimizing the use of combination therapies, to enable patients to derive maximal benefit. PMID- 27188678 TI - Treatment of Multiple Myeloma: Finding the Right Combination. PMID- 27188680 TI - Injecting Hope--A Review of Breast Cancer Vaccines. AB - There is significant interest in investigating immunotherapeutic strategies to be used for the treatment of breast cancer patients. One form of immunotherapy under active investigation is the cancer vaccine. Vaccines are a form of active immune therapy designed to stimulate the immune system to recognize tumor cells as foreign. Vaccines include an antigen that serves as the target for the immune response, and an immunoadjuvant, which is a nonspecific stimulator of the immune response that promotes an environment conducive to immune stimulation. Vaccines are an appealing therapeutic strategy because they are specific and are associated with minimal toxicity. In addition, they stimulate the adaptive immune system, thereby producing a memory response allowing for sustained effect without repeated therapy. Currently, there are no US Food and Drug Administration approved breast cancer vaccines; however, there are multiple vaccines and treatment strategies employing these vaccines that are being actively investigated in clinical trials. PMID- 27188679 TI - How the Affordable Care Act Has Affected Cancer Care in the United States: Has Value for Cancer Patients Improved? PMID- 27188681 TI - Primary Immunoprevention: The Great Unmet Need for Controlling Breast Cancer. PMID- 27188682 TI - 2-Aminoxazole and 2-Aminothiazole Dasatinib Derivatives as Potent Inhibitors of Chronic Myeloid Leukemia K562 Cells. AB - Dasatinib is an important drug against chronic myeloid leukemia (CML). In this paper, we describe the preparation and anti-CML activity of 2-aminoxazole and 2 aminothiazole dasatinib derivatives. Biological activity was measured by the inhibition of proliferation of human CML K562 cells. The 2-aminoxazole derivatives had similar activities as the 2-aminothiazole derivatives. All newly synthesized compounds demonstrated more potent antiproliferative activity than imatinib. A few compounds (8b, 8c, 9b) showed nanomolar inhibitory activity, similar to that of dasatinib. PMID- 27188683 TI - Evaluation of three co-morbidity measures to predict mortality in patients undergoing total joint arthroplasty. AB - OBJECTIVE: To evaluate the 90 days and 1 year mortality predictive ability of the RxRisk-V, Charlson, and Elixhauser co-morbidity measures in total hip arthroplasty (THA) and total knee arthroplasty (TKA) patients. METHOD: A retrospective study of 11,848 THAs and 18,972 TKAs (2001-2002) was conducted. Death within 90 days and 1 year of the surgery were the main endpoints. Co morbidity measures were calculated using either medication or hospitalisation history. Logistic regression models were employed and discrimination and calibration were assessed. Specifically, models with unweighted and weighted measure scores, models with the specific conditions, and a model combining conditions identified by all measures were assessed. RESULTS: In THAs, the best performing prediction models included co-morbidities from all three measures (90 days: c = 0.84, P = 0.284, 1 year: c = 0.79, P = 0.158). Individually, the model with Charlson conditions performed best at 90 days mortality (c = 0.80, P = 0.777) and the Charlson and Elixhauser performed similarly at 1 year (both c = 0.77, P > 0.05). In TKAs, the best performing prediction model included co morbidities from all measures (90 days: c = 0.82, P = 0.349, 1 year: c = 0.78, P = 0.873). Individually, the model with Elixhauser conditions performed best with 90 days mortality (c = 0.79, P = 0.435) and all performed similarly at 1 year (c = 0.74-0.75, all P > 0.05). CONCLUSIONS: A combined model with co-morbidities identified by the Elixhauser, Charlson, and RxRisk-V was the best mortality prediction model. The RxRisk-V did not perform as well as the others. Because of the Elixhauser and Charlson's similar performance we suggest basing the choice of measurement use on factors such as the need of specific conditions and modelling limitations. PMID- 27188684 TI - The prevalence of patellofemoral osteoarthritis: a systematic review and meta analysis. AB - OBJECTIVE: To determine the prevalence of radiographic patellofemoral osteoarthritis (OA) from population- and symptom-based cohorts and to evaluate if knee pain, physical function and quality of life (QOL) differ between people with isolated patellofemoral OA, isolated tibiofemoral OA and combined patellofemoral and tibiofemoral OA. METHOD: Terms associated with "patellofemoral OA", "prevalence" and "clinical features" were used to search Medline, EMBASE, CINAHL, SCOPUS, AMED and Web of Science databases with no language restriction' from inception to August 2014. Two independent reviewers screened papers for eligibility. Studies were included if they reported prevalence of compartmental patterns of radiographic knee OA in population- or symptom-based cohorts. Studies were excluded if they evaluated a targeted sample (e.g., occupation-specific participants) or repeated already reported data from the same cohorts. Point prevalence estimates of patellofemoral OA were extracted from eligible studies, pooled and quantitatively analysed. A critical appraisal tool was used to evaluate methodological quality. RESULTS: The search yielded 1891 records. The inclusion criteria were met by 32 studies. The crude prevalence of patellofemoral OA was 25% in the population-based cohorts (aged >20 years) and 39% in the symptom-based cohorts (aged >30 years). Eight studies reported knee pain, physical function and QOL in people with different compartmental disease; however no significant differences were found. CONCLUSION: These findings confirm the substantial prevalence of patellofemoral OA, demonstrating the need to specifically consider the patellofemoral joint in knee OA research and clinical settings. PMID- 27188685 TI - Knee kinematics and kinetics are associated with early patellofemoral osteoarthritis following anterior cruciate ligament reconstruction. AB - OBJECTIVE: Patellofemoral osteoarthritis (PFOA) commonly occurs following anterior cruciate ligament reconstruction (ACLR). Our study aimed to compare knee kinematics and kinetics during a hop-landing task between individuals with and without early PFOA post-ACLR. DESIGN: Forty-five individuals (mean +/- SD 26 +/- 5 years) 1-2 years post-ACLR underwent 3T isotropic MRI scans and 3D biomechanical assessment of a standardised forward hop task. Knee kinematics (initial contact, peak, excursion) in all three planes and sagittal plane kinetics (peak) were compared between 15 participants with early PFOA (MRI defined patellofemoral cartilage lesion) and 30 participants with no PFOA (absence of patellofemoral cartilage lesion on MRI) using analysis of covariance (ANCOVA), adjusted for age, BMI, sex and the presence of early tibiofemoral OA. RESULTS: Compared to participants without PFOA, those with early PFOA exhibited smaller peak knee flexion angles (mean difference, 95% confidence interval [CI]: 5.2 degrees , -9.9 to -0.4; P = 0.035) and moments (-4.2 Nm/kg.m, -7.8 to -0.6; P = 0.024), and greater knee internal rotation excursion (5.3 degrees , 2.0 to 8.6; P = 0.002). CONCLUSIONS: Individuals with early PFOA within the first 2-years following ACLR exhibit distinct kinematic and kinetic features during a high-load landing task. These findings provide new information regarding common post-ACLR biomechanical patterns and PFOA. Since management strategies, such as altering knee load, are more effective during the early stages of disease, this knowledge will help to inform clinical management of early PFOA post-ACLR. PMID- 27188686 TI - Cerebral palsy. AB - Cerebral palsy is the most common cause of childhood-onset, lifelong physical disability in most countries, affecting about 1 in 500 neonates with an estimated prevalence of 17 million people worldwide. Cerebral palsy is not a disease entity in the traditional sense but a clinical description of children who share features of a non-progressive brain injury or lesion acquired during the antenatal, perinatal or early postnatal period. The clinical manifestations of cerebral palsy vary greatly in the type of movement disorder, the degree of functional ability and limitation and the affected parts of the body. There is currently no cure, but progress is being made in both the prevention and the amelioration of the brain injury. For example, administration of magnesium sulfate during premature labour and cooling of high-risk infants can reduce the rate and severity of cerebral palsy. Although the disorder affects individuals throughout their lifetime, most cerebral palsy research efforts and management strategies currently focus on the needs of children. Clinical management of children with cerebral palsy is directed towards maximizing function and participation in activities and minimizing the effects of the factors that can make the condition worse, such as epilepsy, feeding challenges, hip dislocation and scoliosis. These management strategies include enhancing neurological function during early development; managing medical co-morbidities, weakness and hypertonia; using rehabilitation technologies to enhance motor function; and preventing secondary musculoskeletal problems. Meeting the needs of people with cerebral palsy in resource-poor settings is particularly challenging. PMID- 27188689 TI - The spatial scale of local adaptation in a stochastic environment. AB - The distribution of phenotypes in space will be a compromise between adaptive plasticity and local adaptation increasing the fit of phenotypes to local conditions and gene flow reducing that fit. Theoretical models on the evolution of quantitative characters on spatially explicit landscapes have only considered scenarios where optimum trait values change as deterministic functions of space. Here, these models are extended to include stochastic spatially autocorrelated aspects to the environment, and consequently the optimal phenotype. Under these conditions, the regression of phenotype on the environmental variable becomes steeper as the spatial scale on which populations are sampled becomes larger. Under certain deterministic models - such as linear clines - the regression is constant. The way in which the regression changes with spatial scale is informative about the degree of phenotypic plasticity, the relative scale of effective gene flow and the environmental dependency of selection. Connections to temporal models are discussed. PMID- 27188688 TI - The body project 4 all: A pilot randomized controlled trial of a mixed-gender dissonance-based body image program. AB - OBJECTIVE: The Body Project is a cognitive dissonance-based body image improvement program with ample research support among female samples. More recently, researchers have highlighted the extent of male body dissatisfaction and disordered eating behaviors; however, boys/men have not been included in the majority of body image improvement programs. This study aims to explore the efficacy of a mixed-gender Body Project compared with the historically female only body image intervention program. METHOD: Participants included male and female college students (N = 185) across two sites. We randomly assigned women to a mixed-gender modification of the two-session, peer-led Body Project (MG), the two-session, peer-led, female-only (FO) Body Project, or a waitlist control (WL), and men to either MG or WL. Participants completed self-report measures assessing negative affect, appearance-ideal internalization, body satisfaction, and eating disorder pathology at baseline, post-test, and at 2- and 6-month follow-up. RESULTS: Linear mixed effects modeling to estimate the change from baseline over time for each dependent variable across conditions were used. For women, results were mixed regarding post-intervention improvement compared with WL, and were largely non-significant compared with WL at 6-month follow-up. Alternatively, results indicated that men in MG consistently improved compared with WL through 6 month follow-up on all measures except negative affect and appearance-ideal internalization. DISCUSSION: Results differed markedly between female and male samples, and were more promising for men than for women. Various explanations are provided, and further research is warranted prior to drawing firm conclusions regarding mixed-gender programming of the Body Project. (c) 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2016; 49:591-602). PMID- 27188691 TI - On the general constraints in single qubit quantum process tomography. AB - We briefly review single-qubit quantum process tomography for trace-preserving and nontrace-preserving processes, and derive explicit forms of the general constraints for fitting experimental data. These forms provide additional insight into the structure of the process matrix. We illustrate this with several examples, including a discussion of qubit leakage error models and the intuition which can be gained from their process matrices. PMID- 27188690 TI - Mechanisms for Imparting Conductivity to Nonconductive Polymeric Biomaterials. AB - Traditionally, conductive materials for electrodes are based on high modulus metals or alloys. Development of bioelectrodes that mimic the mechanical properties of the soft, low modulus tissues in which they are implanted is a rapidly expanding field of research. Many polymers exist that more closely match tissue mechanics than metals; however, the majority do not conduct charge. Integrating conductive properties via incorporation of metals and other conductors into nonconductive polymers is a successful approach to producing polymers that can be used in electrical interfacing devices. When combining conductive materials with nonconductive polymer matrices, there is often a tradeoff between the electrical and mechanical properties. This review analyzes the advantages and disadvantages of approaches involving coating or layer formation, composite formation via dispersion of conductive inclusions through polymer matrices, and in situ growth of a conductive network within polymers. PMID- 27188692 TI - The effect of spatial frequency information and visual similarity in threat detection. AB - In the current research, we sought to examine the role of spatial frequency on the detection of threat using a speeded visual search paradigm. Participants searched for threat-relevant (snakes or spiders) or non-threat-relevant (frogs or cockroaches) targets in an array of neutral (flowers or mushrooms) distracters, and we measured search performance with images filtered to contain different levels (high and low) of spatial frequency information. The results replicate previous work demonstrating more rapid detection of threatening versus non threatening stimuli [e.g. LoBue, V. & DeLoache, J. S. (2008). Detecting the snake in the grass: Attention to fear-relevant stimuli by adults and young children. Psychological Science, 19, 284-289. doi:10.1111/j.1467-9280.2008.02081.x]. Most importantly, the results suggest that low spatial frequency or relatively coarse levels of visual information is sufficient for the rapid and accurate detection of threatening stimuli. Furthermore, the results also suggest that visual similarity between the stimuli used in the search tasks plays a significant role in speeded detection. The results are discussed in terms of the theoretical implications for the rapid detection of threat and methodological implications for properly accounting for similarity between the stimuli in visual search studies. PMID- 27188693 TI - Impact of Intraoperative Cone Beam Computed Tomography on Reduction Quality and Implant Position in Treatment of Tibial Plafond Fractures. AB - BACKGROUND: The intraoperative assessment of the articular surface in displaced intra-articular distal tibia fractures can be challenging using conventional fluoroscopy. The aim of the study was to determine the frequency and the method of intraoperative corrections of fracture reductions or implant placements during open reduction, internal fixation by using cone beam computed tomography (CT) after conventional fluoroscopy. METHODS: Displaced intra-articular distal tibia fractures were retrospectively analyzed from August 2001 until December 2011. The fractures were classified according to the standards of the AO/OTA as type B or C and treated with open reduction and internal plate fixation. After primary reduction using conventional fluoroscopy, an additional cone beam CT scan was used to determine the alignment of the joint line and the implant position. The number of intraoperative revisions of the primary reduction due to the use of cone beam CT was analyzed. RESULTS: A total of 143 patients with an intra articular tibial plafond fracture were included in the analysis. In 43 patients (30%), an intraoperative correction was performed after the cone beam CT scan. In 34 (24%) of these cases, intraoperative correction was required because of inadequate joint line reduction. Nine (6%) corrections were required as a result of a malposition of the implant. The revision rate did not differ by fracture classification. CONCLUSION: Despite its acceptance as the standard method of imaging, intraoperative conventional fluoroscopy for the assessment of implant positioning and fracture reduction of tibial plafond fractures is limited. The intraoperative utilization of cone beam CT provided additional information for the surgeon to detect insufficient reduction or implant malposition. LEVEL OF EVIDENCE: Level III, retrospective comparative series. PMID- 27188694 TI - Radiographic Evaluation of Ankle Joint Stability After Calcaneofibular Ligament Elevation During Open Reduction and Internal Fixation of Calcaneus Fracture. AB - BACKGROUND: The aim of this prospective study was to evaluate the influence of sectioning the calcaneofibular ligament (CFL) during an extensile lateral approach during open reduction and internal fixation (ORIF) of calcaneal fractures on ankle joint stability. METHODS: Forty-two patients with calcaneal fractures that received ORIF were included. Talar tilt stress and anterior drawer radiographs were performed on the operative and contralateral ankles 6 months postoperatively. RESULTS: The average degree of talar tilt on stress radiographs was 3.4 degrees (range, 0-12 degrees) on the operative side and 3.2 degrees (range, 0-14 degrees) on the contralateral side. The mean anterior drawer on stress radiographs of the CFL incised ankle was 6.1 mm (range, 2.4-11.8 mm) and on the contralateral ankle was 5.7 mm (range, 2.6-8.6 mm). There was no statistically significant difference of talar tilt and anterior drawer between the CFL incised side and the contralateral side (P = .658 and .302, respectively). CONCLUSION: The results suggest that sectioning of the CFL without any repair during ORIF of a calcaneal fracture does not have a negative effect on stability of the ankle. Repair of the CFL is, thus, probably not necessary following extended lateral approach for ORIF of calcaneal fractures. LEVEL OF EVIDENCE: Level II, comparative study. PMID- 27188695 TI - Supramalleolar Osteotomy With or Without Fibular Osteotomy for Varus Ankle Arthritis. AB - BACKGROUND: Supramalleolar osteotomy (SMOT) is an alternative operative procedure for the management of early and midstage varus ankle arthritis. However, whether fibular osteotomy is needed is controversial. The purpose of the current study was to evaluate the functional and radiologic outcomes of pre- and postoperative SMOT, and to compare the outcomes between patients with and without fibular osteotomy. METHODS: Forty-one Takakura stage 2 and 3 varus ankle osteoarthritis patients treated with SMOT were included. Fourteen males and 27 females with a mean age of 50.7 (range, 32-71) years were followed with a mean of 36.6 (range, 17-61) months. There were 22 cases with fibular osteotomy and 19 without. The American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot score, Maryland foot score, and Ankle Osteoarthritis Score (AOS) were used for pre- and postoperative functional evaluation. The tibial articular surface angle (TAS), talar tilt (TT), tibiocrural angle (TC), and tibial lateral surface angle (TLS) were evaluated pre- and postoperatively. RESULTS: At the last follow-up, the mean AOFAS score (from 50.8 to 83.1 points) and Maryland score (from 58.3 to 81.6 points) in overall were improved (P < .01); the mean AOS pain (from 42.6 to 26.1 points) and function (from 53.4 to 36.8 points) scores were decreased (P < .01). For radiologic evaluation, all the included parameters were improved (P < .05) except TLS. The mean Takakura stage was decreased (P < .01). No significant difference could be detected in comparing the functional outcomes between those with and without fibular osteotomy. However, in the fibular osteotomy group, TT was decreased (P < .05) and TC was improved (P < .01) significantly. CONCLUSION: SMOT was promising, with substantial functional improvement and malalignment correction for varus ankle arthritis. Fibular osteotomy may be necessary in cases with large TT and small TC angles. LEVEL OF EVIDENCE: Level III, retrospective comparative study. PMID- 27188687 TI - Kidney stones. AB - Kidney stones are mineral deposits in the renal calyces and pelvis that are found free or attached to the renal papillae. They contain crystalline and organic components and are formed when the urine becomes supersaturated with respect to a mineral. Calcium oxalate is the main constituent of most stones, many of which form on a foundation of calcium phosphate called Randall's plaques, which are present on the renal papillary surface. Stone formation is highly prevalent, with rates of up to 14.8% and increasing, and a recurrence rate of up to 50% within the first 5 years of the initial stone episode. Obesity, diabetes, hypertension and metabolic syndrome are considered risk factors for stone formation, which, in turn, can lead to hypertension, chronic kidney disease and end-stage renal disease. Management of symptomatic kidney stones has evolved from open surgical lithotomy to minimally invasive endourological treatments leading to a reduction in patient morbidity, improved stone-free rates and better quality of life. Prevention of recurrence requires behavioural and nutritional interventions, as well as pharmacological treatments that are specific for the type of stone. There is a great need for recurrence prevention that requires a better understanding of the mechanisms involved in stone formation to facilitate the development of more effective drugs. PMID- 27188696 TI - Radiographic and CT Assessment of Reduction of Calcaneus Fractures Using a Limited Sinus Tarsi Incision. AB - BACKGROUND: The lateral extensile incision for fixation of displaced intra articular calcaneus fractures allows for fracture reduction but has been associated with high rates of soft tissue complications. This has prompted a search for less invasive methods of fracture fixation. The purpose of the present study was to determine the adequacy of reduction and rate of complications associated with operative fixation of calcaneal fractures using a limited sinus tarsi approach. METHODS: A limited sinus tarsi incision with plate fixation was utilized for treatment of 39 displaced intra-articular calcaneal fractures in 35 consecutive patients as part of a single surgeon series. Imaging assessment of previously described fracture displacement measures was undertaken in preoperative and postoperative radiographs and CT. A retrospective chart review was conducted to identify postoperative complications. RESULTS: Mean preoperative Bohler angle measurement was 7.7 (range, -26.0 to 30.0) degrees and the mean final postoperative standing Bohler angle was 25.5 (range, 12.3 to 37.7) degrees. Postoperative CT demonstrated that subtalar articular reduction was within 2 mm of anatomic in 91% of patients. There were 2 instances of superficial wound dehiscence (5.1%) and 1 deep infection (2.6%) that required debridement and complete hardware removal. Visual analog score (VAS) for pain averaged 3 of 10 in the 32 available patients at 1-year follow-up. Eight of these patients (25%) reported no pain (0/10) at final follow-up. CONCLUSION: Operative fixation of displaced intra-articular calcaneal fractures utilizing the limited sinus tarsi approach resulted in acceptable fracture reduction and a low rate of complications. LEVEL OF EVIDENCE: Level IV, retrospective case series. PMID- 27188697 TI - Evolution of Moire Profiles from van der Waals Superstructures of Boron Nitride Nanosheets. AB - Two-dimensional (2D) van der Waals (vdW) superstructures, or vdW solids, are formed by the precise restacking of 2D nanosheet lattices, which can lead to unique physical and electronic properties that are not available in the parent nanosheets. Moire patterns formed by the crystalline mismatch between adjacent nanosheets are the most direct features for vdW superstructures under microscopic imaging. In this article, transmission electron microscopy (TEM) observation of hexagonal Moire patterns with unusually large micrometer-sized lateral areas (up to ~1 MUm(2)) and periodicities (up to ~50 nm) from restacking of liquid exfoliated hexagonal boron nitride nanosheets (BNNSs) is reported. This observation was attributed to the long range crystallinity and the contaminant free surfaces of these chemically inert nanosheets. Parallel-line-like Moire fringes with similarly large periodicities were also observed. The simulations and experiments unambiguously revealed that the hexagonal patterns and the parallel fringes originated from the same rotationally mismatched vdW stacking of BNNSs and can be inter-converted by simply tilting the TEM specimen following designated directions. This finding may pave the way for further structural decoding of other 2D vdW superstructure systems with more complex Moire images. PMID- 27188698 TI - The effect of tranexamic acid on the risk of death and hysterectomy in women with post-partum haemorrhage: statistical analysis plan for the WOMAN trial. AB - BACKGROUND: Severe haemorrhage is a leading cause of maternal death worldwide. Most haemorrhage deaths occur soon after childbirth. Severe post-partum bleeding is sometimes managed by the surgical removal of the uterus (hysterectomy). Death and hysterectomy are important health consequences of post-partum haemorrhage, and clinical trials of interventions aimed at preventing these outcomes are needed. METHODS: The World Maternal Antifibrinolytic trial aims to determine the effect of tranexamic acid on death, hysterectomy and other health outcomes in women with post-partum haemorrhage. It is an international, multicentre, randomised trial. Approximately 20,000 women with post-partum haemorrhage will be randomly allocated to receive an intravenous injection of either tranexamic acid or matching placebo in addition to usual care. The primary outcome measure is a composite of death in hospital or hysterectomy within 42 days of delivery. The cause of death will be described. Secondary outcomes include death, death due to bleeding, hysterectomy, thromboembolic events, blood transfusion, surgical and radiological interventions, complications, adverse events and quality of life. The health status and occurrence of thromboembolic events in breastfed babies will also be reported. We will conduct subgroup analyses for the primary outcome by time to treatment, type of delivery and cause of haemorrhage. We will conduct an analysis of treatment effect adjusted for baseline risk. DISCUSSION: The World Maternal Antifibrinolytic trial should provide reliable evidence for the efficacy of tranexamic acid in the prevention of death, hysterectomy and other outcomes that are important to patients. We present a protocol update and the statistical analysis plan for the trial. TRIAL REGISTRATION: Current Controlled Trials ISRCTN76912190 (Registration date 08 December 2008), Clinicaltrials.gov NCT00872469 (Registration date 30 March 2009) and Pan African Clinical Trials Registry: PACTR201007000192283 (Registration date 02 September 2010). PMID- 27188699 TI - A Treatment Approach to Catamenial Epilepsy. AB - OPINION STATEMENT: The cyclic hormonal underpinnings of catamenial seizure exacerbations are consistent with the neurophysiologic activity of estrogen and progesterone. For women with catamenial epilepsy who have regular menses, intermittent treatment approaches may be utilized. These interventions are targeted at adding or increasing anti-seizure treatments during established vulnerable days of the menstrual cycle, such as perimenstrually (C1 pattern), at ovulation (C2 pattern), and during the luteal phase (C3 pattern). The single large study of natural progesterone treatment showed benefit for women with clear perimenstrual seizure exacerbations (C1 pattern), but not for subjects with other catamenial patterns or for randomized women with epilepsy of reproductive age who did not have catamenial seizure exacerbations. In this protocol, natural progesterone was given at a high dose during the luteal phase and was generally well tolerated. Other intermittent cyclic treatments include benzodiazepine use, increasing the dose of an anti-seizure drug already in use, or acetazolamide. For women with irregular menses, or those in which the intermittent cyclic treatments are not effective, pharmacologically stopping the menstrual cycle altogether by using synthetic hormones such as medroxyprogesterone (Depo-Provera) or sustained oral contraceptives may be considered. PMID- 27188701 TI - Economic impact of recurrent respiratory papillomas in a UK adult population. AB - OBJECTIVE: To calculate the financial burden of recurrent respiratory papilloma. This study is UK-based, where up until now no financial estimates have been calculated for this group of patients. BACKGROUND: Recurrent respiratory papilloma is caused by the human papilloma virus (subtypes 6 and 11). The burden for the patient and the healthcare system is significant given the recurrent nature of the disease. METHODS: Data were collected, using a questionnaire completed during routine clinical follow up, from a single centre managing recurrent respiratory papilloma in Glasgow, Scotland. Cost information was sourced from the Scottish Government's Information Services Division. RESULTS: Fourteen patients with active recurrent respiratory papilloma between 2013 and 2014 were identified. The direct measurable cost to NHS Greater Glasgow and Clyde amounted to L107 478. CONCLUSION: Recurrent respiratory papilloma is a benign condition, but the financial implications of diagnosis are significant. Recurrent respiratory papilloma has a natural history of relapse and remission, and patients may require healthcare input over a period of several years. PMID- 27188700 TI - Use of the Physician Orders for Life-Sustaining Treatment among California Nursing Home Residents. AB - BACKGROUND: Physician Orders for Life-Sustaining Treatment (POLST) is a tool that facilitates the elicitation and continuity of life-sustaining care preferences. POLST was implemented in California in 2009, but how well it disseminated across a large, racially diverse population is not known and has implications for end-of life care. OBJECTIVE: To evaluate the use of POLST among California nursing home residents, including variation by resident characteristics and by nursing home facility. DESIGN: Observational study using California Minimum Data Set Section S. PARTICIPANTS: A total of 296,276 people with a stay in 1,220 California nursing homes in 2011. MAIN MEASURES: The proportion of residents with a completed POLST (containing a resuscitation status order and resident/proxy and physician signatures) and relationship to resident characteristics; change in POLST use during 2011; and POLST completion and unsigned forms within nursing homes. KEY RESULTS: During 2011, POLST completion increased from 33 to 49 % of California nursing home residents. Adjusting for age and gender using a mixed effects logistic model, long-stay residents were more likely than short-stay residents to have a completed POLST [OR = 2.36 (95 % CI 2.30, 2.42)]; severely cognitively impaired residents were less likely than unimpaired to have a completed POLST [OR = 0.89 (95 % CI 0.87, 0.92)]; and there was little difference by functional status. There was no difference in POLST completion among White non Hispanic, Black, and Hispanic residents. Variation in POLST completion among nursing homes far exceeded that attributable to resident characteristics with 40 % of facilities having >=80 % of long-stay residents with a completed POLST, while 20 % of facilities had <=10 % of long-stay residents with a completed POLST. Thirteen percent of nursing home residents had a POLST containing a resuscitation preference but lacked a signature, rendering the POLST invalid. CONCLUSIONS: Statewide nursing home data show broad uptake of POLST in California without racial disparity. However, variation in POLST completion among nursing homes identifies potential areas for quality improvement. PMID- 27188702 TI - Phase 3 Trials of Thermosensitive Ciprofloxacin Gel for Middle Ear Effusion in Children with Tubes. AB - OBJECTIVE: To investigate the efficacy, safety, and microbiology of a thermosensitive otic suspension of ciprofloxacin (OTO-201) in children with bilateral middle ear effusion undergoing tympanostomy tube placement. STUDY DESIGN: Two randomized, double-blind, sham-controlled phase 3 trials. Patients were randomized to intratympanic OTO-201 or sham. SETTING: Children with bilateral middle ear effusion undergoing tympanostomy tube placement. SUBJECTS/METHODS: Studies evaluated 532 patients (6 months to 17 years old) in a combined analysis of efficacy (treatment failure: presence of otorrhea, otic or systemic antibiotic use, lost to follow-up, missed visits), safety (audiometry, otoscopy, tympanometry), and microbiology. RESULTS: There was a lower cumulative proportion of treatment failures in patients receiving OTO-201 vs tympanostomy tubes alone (1) on days 4, 8, 15, and 29; (2) on day 15, primary end point (23.0% vs 45.1%; age-adjusted odds ratio, 0.341; P < .001; reduction in relative risk, 49%); and (3) on day 15, blinded-assessor otorrhea treatment failure (7.0% vs 19.4%; age-adjusted odds ratio, 0.303; P < .001; reduction in relative risk, 64%). Per-protocol and subgroup analyses (baseline demographics, pathogen type, culture status, effusion type, microbiologic response) supported these findings. There were no drug-related serious adverse events; the most frequent treatment emergent adverse events in both groups were pyrexia, postoperative pain, nasopharyngitis, cough, and upper respiratory tract infection. OTO-201 administration had no evidence of increased tube occlusion and no negative effect on audiometry, tympanometry, or otoscopy. CONCLUSIONS: Combined analysis of 2 phase 3 trials demonstrated a lower cumulative proportion of treatment failures through day 15 compared with TT alone when OTO-201 was administered intratympanically for otitis media with bilateral middle ear effusion at time of tympanostomy tube placement. PMID- 27188703 TI - Psychometric Validation of a Moroccan Version of the 22-Item Sino-Nasal Outcome Test. AB - OBJECTIVE: The objective of this study paper was to culturally adapt and validate the 22-item Sino-Nasal Outcome Test (SNOT-22) questionnaire for Moroccan Arabic speaking patients. STUDY DESIGN: Prospective cohort study. SETTING: Tertiary referral center; Ibn Rochd University Hospital, Casablanca, Morocco. SUBJECTS AND METHODS: The SNOT-22 was conducted in patients with chronic rhinosinusitis (CRS) undergoing sinonasal surgery and in healthy volunteers, from January 2012 to December 2013. It was translated into Moroccan Arabic language. To evaluate this questionnaire, internal consistency, test-retest reliability, responsiveness to treatment, and validity were analyzed. RESULTS: Preoperative SNOT-22 scores were completed by 88 patients. Six-month postoperative SNOT-22 scores were available for 74 patients. The Cronbach's alpha coefficient for the SNOT-22 was 0.968, indicating high internal consistency. The test-retest reliability coefficient was 0.993, indicating high reliability when administering the instrument on repeated occasions. The Moroccan version of the SNOT-22 was able to highly discriminate between patients with CRS and group of healthy volunteers (P < .0001). There was a statistically significant reduction in patient reported SNOT-22 scores at 6 months after surgery (P < .0001). CONCLUSION: The present study has found the Moroccan version of SNOT-22 to be valid and easy to use with good reliability, validity, and responsiveness. It can be used to measure the impact of CRS on the patient's quality of life and may also be used to evaluate CRS treatment. PMID- 27188705 TI - Improving Access to Head and Neck Cancer Surgical Services through the Incorporation of Associate Providers. AB - OBJECTIVE: The urgent nature of head and neck cancer referrals often results in overbooked schedules, access delays, and patient, physician, and staff dissatisfaction. The goal of this study is to examine how incorporation of associate providers (APs) into a head and neck tumor clinic (HNTC) can improve access. METHODS: Scheduling data for the Dartmouth-Hitchcock HNTC 2 years prior (January 2011 to December 2012) and 2 years subsequent (January 2013 to December 2014) to program initiation were abstracted, including number of new patients seen per month, third available for new and established patients, overbooked hours, surgeon productivity, and patient satisfaction scores. RESULTS: New patients seen per month increased from 44 +/- 4 to 60 +/- 5 (P < .001). Third available for new patients decreased from 56 +/- 4 to 27 +/- 2 days and from 43 +/- 3 to 35 +/- 2 days for follow-ups (P < .001). Overbooked hours decreased from 14.7 +/- 3.1 to 8.6 +/- 1.7 hours (P < .001). Surgeon productivity remained stable (109% +/- 11% vs 113% +/- 6%, P = .56). Patient satisfaction in seeing APs versus surgeons was comparable (94 +/- 2 vs 94 +/- 3, P = .79). DISCUSSION: Incorporation of APs into the HNTC increases the number of new patients seen by the surgeon, decreases wait times for all appointments, and decreases overbooking while maintaining patient satisfaction and surgeon productivity. IMPLICATIONS FOR PRACTICE: AP incorporation significantly improves access to head and neck surgical services. With improved access, new cancer patients could start treatment sooner, potentially affecting outcome. PMID- 27188704 TI - The Use of Ibuprofen in Posttonsillectomy Analgesia and Its Effect on Posttonsillectomy Hemorrhage Rate. AB - OBJECTIVE: To determine the effect of ibuprofen on posttonsillectomy bleeding when compared with codeine in posttonsillectomy analgesia. STUDY DESIGN: Case series with chart review. SETTING: Tertiary care children's hospital, Philadelphia, Pennsylvania. SUBJECTS AND METHODS: On July 1, 2012, our institution transitioned from acetaminophen with codeine to ibuprofen for posttonsillectomy analgesia. Pediatric patients (0-18 years old) who underwent surgery from July 1, 2010, to June 30, 2012, were placed in the codeine cohort, and those who underwent surgery from July 1, 2012, to June 30, 2014, were placed in the ibuprofen cohort. RESULTS: A total of 6014 patients underwent tonsillectomy between July 1, 2010, and June 30, 2014, and 211 patients presented for posttonsillectomy hemorrhage during the same period. The incidence of readmission for posttonsillectomy hemorrhage was 3.4% and 3.6% (P = .63; odds ratio [OR] = 1.07; 95% confidence interval [95% CI]: 0.811-1.410) for the codeine and ibuprofen groups, respectively, and the incidence of second operation for control of posttonsillectomy bleeding for the codeine and ibuprofen groups was 1.9% and 2.2% (P = .54; OR = 1.117; 95% CI: 0.781-1.600), respectively. Patients aged 11 to 18 years demonstrated a higher incidence of posttonsillectomy bleeding events overall. When age is controlled, multivariate logistic regression demonstrated no statistically significant increase in posttonsillectomy bleeding events among pediatric patients treated with ibuprofen versus patients treated with codeine (readmission: P = .617; OR = 0.932; 95% CI: 0.707-1.228; reoperation: P = .513; OR = 0.887; 95% CI: 0.618-1.272). CONCLUSION: Age is an independent risk factor for posttonsillectomy bleeding. When age is controlled, there is no statistically significant increase in the incidence of posttonsillectomy bleeding events among patients treated with ibuprofen when compared to patients treated with codeine. PMID- 27188706 TI - Adverse Event Reporting for Proton Pump Inhibitor Therapy: An Overview of Systematic Reviews. AB - OBJECTIVE: To assist clinicians in counseling patients regarding the risk of adverse events from proton pump inhibitors (PPIs), by synthesizing evidence from published systematic reviews of antireflux therapy. DATA SOURCES: Cochrane Library, CINAHL, PubMed, Web of Knowledge. REVIEW METHODS: Overview based on PRISMA reporting standards (preferred reporting items for systematic reviews and meta-analyses) of English-language meta-analyses and systematic reviews of PPI therapy for reflux disease through December 2014. Two independent investigators assessed study eligibility, rated the review quality with AMSTAR criteria (assessing the methodological quality of systematic reviews), and abstracted data for adverse events. RESULTS: Thirty-three systematic reviews met inclusion criteria. The most commonly reported adverse events were community-acquired pneumonia (odds ratios, 1.04-1.92), with a greater association noted with shorter duration of therapy and higher doses. Hip fractures were also associated with PPI use (odds ratios, 1.16-1.50), especially with long-term therapy. Last, enteric infection with Clostridium difficile was more common with PPI therapy (odds ratios, 1.69-1.33). Other less commonly reported adverse events included electrolyte and vitamin deficiency. Risk factors for adverse events are reported in the text. CONCLUSION: Our overview shows that PPI therapy is associated with significant and potentially serious adverse events that should be discussed with patients. The effect sizes and risk factors provided should facilitate this discussion and promote shared decision making. PMID- 27188708 TI - Same-Day Evaluation and Surgery for Otitis Media and Tympanostomy Tube Placement: A Feasibility Study. AB - OBJECTIVE: To determine the feasibility of providing streamlined same-day evaluation and surgical management of children with recurrent otitis media or chronic serous otitis media who meet criteria for tympanostomy tube (TT) placement. STUDY DESIGN: Retrospective matched case series. SETTING: Tertiary care children's hospital. METHODS: A comparison group (age, sex, insurance product) was utilized to determine if the same-day process decreased facility time and surgical time for the care episode. A parent satisfaction survey was administered. RESULTS: Thirty children, with a median age of 16 months (range, 12 22 months), participated in the same-day surgery process for TT. Twenty-one patients (70.0%) were male, and these patients were matched to a comparison group (similar age, sex, and insurance product) having non-same-day (routine) TT placement. The same-day patients spent significantly less time in clinic for the preoperative physician visit (average, 15 minutes) when compared with the non same-day patients (average, 51.5 minutes; P < .001). The operative experience for the same-day patients was similar to the non-same-day patients (average, 145 vs 137 minutes, respectively; P = .35), but the overall experience was significantly shorter for the same-day patients (average, 151 vs 196 minutes for comparisons; P < .001). All parents surveyed in the same-day group were satisfied with the efficiency of the experience. CONCLUSION: The same-day surgery process for management of children who meet the criteria for TT placement is a model of improved efficiency of care for children who suffer from otitis media. PMID- 27188710 TI - Postcolonial Ecologies of Parasite and Host: Making Parasitism Cosmopolitan. AB - The interest of F. Macfarlane Burnet in host-parasite interactions grew through the 1920s and 1930s, culminating in his book, Biological Aspects of Infectious Disease (1940), often regarded as the founding text of disease ecology. Our knowledge of the influences on Burnet's ecological thinking is still incomplete. Burnet later attributed much of his conceptual development to his reading of British theoretical biology, especially the work of Julian Huxley and Charles Elton, and regretted he did not study Theobald Smith's Parasitism and Disease (1934) until after he had formulated his ideas. Scholars also have adduced Burnet's fascination with natural history and the clinical and public health demands on his research effort, among other influences. I want to consider here additional contributions to Burnet's ecological thinking, focusing on his intellectual milieu, placing his research in a settler society with exceptional expertise in environmental studies and pest management. In part, an ''ecological turn'' in Australian science in the 1930s, derived to a degree from British colonial scientific investments, shaped Burnet's conceptual development. This raises the question of whether we might characterize, in postcolonial fashion, disease ecology, and other studies of parasitism, as successful settler colonial or dominion science. PMID- 27188707 TI - Dystonia-Causing Mutations as a Contribution to the Etiology of Spasmodic Dysphonia. AB - OBJECTIVE: Spasmodic dysphonia is a focal dystonia of the larynx with heterogeneous manifestations and association with familial risk factors. There are scarce data to allow precise understanding of etiology and pathophysiology. Screening for dystonia-causing genetic mutations has the potential to allow accurate diagnosis, inform about genotype-phenotype correlations, and allow a better understanding of mechanisms of disease. STUDY DESIGN: Cross-sectional study. SETTING: Tertiary academic medical center. SUBJECTS AND METHODS: We enrolled patients presenting with spasmodic dysphonia to the voice clinic of our academic medical center. Data included demographics, clinical features, family history, and treatments administered. The following genes with disease-causing mutations previously associated with spasmodic dysphonia were screened: TOR1A (DYT1), TUBB4 (DYT4), and THAP1 (DYT6). RESULTS: Eighty-six patients were recruited, comprising 77% females and 23% males. A definite family history of neurologic disorder was present in 15% (13 of 86). Average age (+/- standard deviation) of symptom onset was 42.1 +/- 15.7 years. Most (99%; 85 of 86) were treated with botulinum toxin, and 12% (11 of 86) received oral medications. Genetic screening was negative in all patients for the GAG deletion in TOR1A (DYT1) and in the 5 exons currently associated with disease-causing mutations in TUBB4 (DYT4). Two patients tested positive for novel/rare variants in THAP1 (DYT6). CONCLUSION: Genetic screening targeted at currently known disease-causing mutations in TOR1A, THAP1, and TUBB4 appears to have low diagnostic yield in sporadic spasmodic dysphonia. In our cohort, only 2 patients tested positive for novel/rare variants in THAP1. Clinicians should make use of genetic testing judiciously and in cost-effective ways. PMID- 27188709 TI - The relationship between mitochondrial DNA haplotype and the reproductive capacity of domestic pigs (Sus scrofa domesticus). AB - BACKGROUND: The maternally inherited mitochondrial genome encodes key proteins of the electron transfer chain, which produces the vast majority of cellular ATP. Mitochondrial DNA (mtDNA) present in the mature oocyte acts as a template for all mtDNA that is replicated during development to meet the specific energy requirements of each tissue. Individuals that share a maternal lineage cluster into groupings known as mtDNA haplotypes. MtDNA haplotypes confer advantages and disadvantages to an organism and this affects its phenotype. In livestock, certain mtDNA haplotypes are associated with improved milk and meat quality, whilst, other species, mtDNA haplotypes have shown increased longevity, growth and susceptibility to diseases. In this work, we have set out to determine whether mtDNA haplotypes influence reproductive capacity. This has been undertaken using a pig model. RESULTS: To determine the genetic diversity of domestic pigs in Australia, we have sequenced the D-loop region of 368 pigs, and identified five mtDNA haplotypes (A to E). To assess reproductive capacity, we compared oocyte maturation, fertilization and development to blastocyst, and found that there were significant differences for maturation and fertilization amongst the haplotypes. We then determined that haplotypes C, D and E produced significantly larger litters. When we assessed the conversion of developmentally competent oocytes and their subsequent developmental stages to offspring, we found that haplotypes A and B had the lowest reproductive efficiencies. Amongst the mtDNA haplotypes, the number of mtDNA variants harbored at >25 % correlated with oocyte quality. MtDNA copy number for developmentally competent oocytes positively correlated with the level of the 16383delC variant. This variant is located in the conserved sequence box II, which is a regulatory region for mtDNA transcription and replication. CONCLUSIONS: We have identified five mtDNA haplotypes in Australian domestic pigs indicating that genetic diversity is restricted. We have also shown that there are differences in reproductive capacity amongst the mtDNA haplotypes. We conclude that mtDNA haplotypes affect pig reproductive capacity and can be used as a marker to complement current selection methods to identify productive pigs. PMID- 27188711 TI - Alanine aminotransferase controls seed dormancy in barley. AB - Dormancy allows wild barley grains to survive dry summers in the Near East. After domestication, barley was selected for shorter dormancy periods. Here we isolate the major seed dormancy gene qsd1 from wild barley, which encodes an alanine aminotransferase (AlaAT). The seed dormancy gene is expressed specifically in the embryo. The AlaAT isoenzymes encoded by the long and short dormancy alleles differ in a single amino acid residue. The reduced dormancy allele Qsd1 evolved from barleys that were first domesticated in the southern Levant and had the long dormancy qsd1 allele that can be traced back to wild barleys. The reduced dormancy mutation likely contributed to the enhanced performance of barley in industrial applications such as beer and whisky production, which involve controlled germination. In contrast, the long dormancy allele might be used to control pre-harvest sprouting in higher rainfall areas to enhance global adaptation of barley. PMID- 27188712 TI - Best Albuminuria Measurement to Predict Cardiovascular and Renal Events. AB - BACKGROUND: Kidney Disease Improving Global Outcomes (KDIGO) guidelines encourage clinicians to estimate 24-hour albuminuria as albumin to creatinine ratio (ACR) from spot urine samples. However, ACR underestimates 24-hour albumin excretion in muscular individuals. Equations that adjust ACR for surrogates of muscle mass to yield an estimated albumin excretion rate (eAER) were developed. We hypothesised that eAER is a better predictor of cardiovascular and renal outcomes than ACR. METHODS: We determined ACR and eAER among 443 patients with chronic kidney disease G2-G4 recruited into the CARE FOR HOMe study. Patients were classified into KDIGO albuminuria categories, and followed for cardiovascular and renal events. The primary analysis was the net reclassification improvement (NRI) for those with and without events within 3 years of follow-up. RESULTS: Eighty five patients experienced cardiovascular events during 3 years of follow-up, 13 of whom were reclassified to a more advanced albuminuria category, and 1 patient to a less advanced category by eAER compared to ACR (NRIevent: 14.1% (95% CI 5.8 22.4)). Among 358 patients without a cardiovascular event, 17 patients were reclassified to a more advanced albuminuria category, and 2 patients to a less advanced category by eAER (NRIno event: -4.2%, 95% CI -8.5 to -1.8). Sixty patients went through renal events, and 383 patients had event-free 3-year follow up. NRIevent was 6.7% (95% CI -1.2 to 14.5), and NRIno event was -6.0% (95% CI 10.6 to 3.4) for renal events. CONCLUSION: Compared to ACR albuminuria categories, eAER categories are better associated with future cardiovascular events, but not with renal events. PMID- 27188713 TI - A new data-driven model for post-transplant antibody dynamics in high risk kidney transplantation. AB - The dynamics of donor specific human leukocyte antigen antibodies during early stage after kidney transplantation are of great clinical interest as these antibodies are considered to be associated with short and long term clinical outcomes. The limited number of antibody time series and their diverse patterns have made the task of modelling difficult. Focusing on one typical post transplant dynamic pattern with rapid falls and stable settling levels, a novel data-driven model has been developed for the first time. A variational Bayesian inference method has been applied to select the best model and learn its parameters for 39 time series from two groups of graft recipients, i.e. patients with and without acute antibody-mediated rejection (AMR) episodes. Linear and nonlinear dynamic models of different order were attempted to fit the time series, and the third order linear model provided the best description of the common features in both groups. Both deterministic and stochastic parameters are found to be significantly different in the AMR and no-AMR groups showing that the time series in the AMR group have significantly higher frequency of oscillations and faster dissipation rates. This research may potentially lead to better understanding of the immunological mechanisms involved in kidney transplantation. PMID- 27188715 TI - Quantum Critical Behavior in a Concentrated Ternary Solid Solution. AB - The face centered cubic (fcc) alloy NiCoCrx with x ~ 1 is found to be close to the Cr concentration where the ferromagnetic transition temperature, Tc, goes to 0. Near this composition these alloys exhibit a resistivity linear in temperature to 2 K, a linear magnetoresistance, an excess -TlnT (or power law) contribution to the low temperature heat capacity, and excess low temperature entropy. All of the low temperature electrical, magnetic and thermodynamic properties of the alloys with compositions near x ~ 1 are not typical of a Fermi liquid and suggest strong magnetic fluctuations associated with a quantum critical region. The limit of extreme chemical disorder in this simple fcc material thus provides a novel and unique platform to study quantum critical behavior in a highly tunable system. PMID- 27188714 TI - The role of electrical coupling in generating and modulating oscillations in a neuronal network. AB - A simplified model of the crustacean gastric mill network is considered. Rhythmic activity in this network has largely been attributed to half center oscillations driven by mutual inhibition. We use mathematical modeling and dynamical systems theory to show that rhythmic oscillations in this network may also depend on, or even arise from, a voltage-dependent electrical coupling between one of the cells in the half-center network and a projection neuron that lies outside of the network. This finding uncovers a potentially new mechanism for the generation of oscillations in neuronal networks. PMID- 27188716 TI - Analysis of the dose-dependent stage-specific in vitro efficacy of a multi-stage malaria vaccine candidate cocktail. AB - BACKGROUND: The high incidence and mortality rate of malaria remains a serious burden for many developing countries, and a vaccine that induces durable and highly effective immune responses is, therefore, desirable. An earlier analysis of the stage-specific in vitro efficacy of a malaria vaccine candidate cocktail (VAMAX) considered the general properties of complex multi-component, multi-stage combination vaccines in rabbit immunization experiments using a hyper immunization protocol featuring six consecutive boosts and a strong, lipopolysaccharide-based adjuvant. This follow-up study investigates the effect of antigen dose on the in vitro efficacy of the malaria vaccine cocktail using a conventional vaccination scheme (one prime and two boosts) and a human-compatible adjuvant (Alhydrogel((r))). RESULTS: IgG purified from rabbits immunized with 0.1, 1, 10 or 50 ug doses of the VAMAX vaccine candidate cocktail was analysed for total IgG and antigen-cocktail-specific titers. An increase in cocktail specific titers was observed between 0.1 and 1 ug and between 10 and 50 ug, whereas no significant difference in titers was observed between 1 and 10 ug. Antigen component-specific antibody titers and stage-specific in vitro efficacy assays were performed with pooled IgG from animals immunized with 1 and 50 ug of the VAMAX cocktail. Here, the component-specific antibody levels showed clear dose dependency whereas the determined stage-specific in vitro IC50 values (as a correlate of efficacy) were only dependent on the titer amounts of stage-specific antibodies. CONCLUSIONS: The stage-specific in vitro efficacy of the VAMAX cocktail strongly correlates with the corresponding antigen-specific titers, which for their part depend on the antigen dose, but there is no indication that the dose has an effect on the in vitro efficacy of the induced antibodies. A comparison of these results with those obtained in the previous hyper immunization study (where higher levels of antigen-specific IgG were observed) suggests that there is a significant need to induce an immune response matching efficacy requirements, especially for a PfAMA1-based blood stage vaccine, by using higher doses, better adjuvants and/or better formulations. PMID- 27188718 TI - Marinirhabdus gelatinilytica gen. nov., sp. nov., isolated from seawater. AB - A Gram-stain-negative, aerobic and slightly halophilic bacterium was isolated from the South China Sea, and was subjected to characterization using a polyphasic taxonomic approach. Cells of the isolate, designated NH83T, were non motile and rod-shaped. On the basis of 16S rRNA gene sequence analysis, strain NH83Twas closely related to members of the genera Aureisphaera (with sequence similarity of 92.9 %), Jejudonia (92.8 %), Marixanthomonas (92.6 %), Altuibacter (92.6 %), Ulvibacter (91.5-91.9 %), Gilvibacter (91.8 %) and Aequorivita (89.6 91.2 %), all of which belong to the family Flavobacteriaceae. Phylogenetic analysis indicated that it represented an independent lineage and its closest relatives belonged to the genus Marixanthomonas. The sole respiratory quinone was MK-6. The major polar lipids were phosphatidylethanolamine, two aminolipids, one aminophospholipid and one unidentified lipid. The principal fatty acids were branched fatty acids, including iso-C15 : 0, iso-C17 : 0 3-OH, iso-C16 : 0, iso C15 : 1 G and summed feature 3 (iso-C15 : 0 2-OH and/or C16 : 1omega7c). The genomic DNA G+C content was 41.0 mol%. Strain NH83T was positive for hydrolysis of aesculin, gelatin and Tween 60. Phylogenetic distinctiveness and chemotaxonomic differences, together with differential phenotypic properties, revealed that strain NH83T could be differentiated from closely related genera. Therefore, it is proposed that strain NH83T represents a novel species in a new genus, for which the name Marinirhabdus gelatinilytica gen. nov., sp. nov. (type strain NH83T=CGMCC 1.15462T=DSM 101478T) is proposed. PMID- 27188717 TI - An 18 gene expression-based score classifier predicts the clinical outcome in stage 4 neuroblastoma. AB - BACKGROUND: The prognosis of children with metastatic stage 4 neuroblastoma (NB) has remained poor in the past decade. PATIENTS AND METHODS: Using microarray analyses of 342 primary tumors, we here developed and validated an easy to use gene expression-based risk score including 18 genes, which can robustly predict the outcome of stage 4 patients. RESULTS: This classifier was a significant predictor of overall survival in two independent validation cohorts [cohort 1 (n = 214): P = 6.3 * 10(-5); cohort 2 (n = 27): P = 3.1 * 10(-2)]. The prognostic value of the risk score was validated by multivariate analysis including the established markers age and MYCN status (P = 0.027). In the pooled validation cohorts (n = 241), integration of the risk score with the age and/or MYCN status identified subgroups with significantly differing overall survival (ranging from 35 to 100 %). CONCLUSION: Together, the 18-gene risk score classifier can identify patients with stage 4 NB with favorable outcome and may therefore improve risk assessment and treatment stratification of NB patients with disseminated disease. PMID- 27188719 TI - Patient attitudes towards outpatient cervical ripening prior to induction of labour at an Australian tertiary hospital. AB - A prospective patient questionnaire was conducted to assess attitudes and opinions towards outpatient cervical ripening in women attending an Australian tertiary hospital's labour and birth suite for a booked induction of labour. Questionnaires were distributed over a three-month period and information collected included demographic data, pregnancy and obstetric history, attitudes towards cervical ripening and willingness to undergo cervical ripening in the outpatient setting. Responses to 57 completed questionnaires were analysed. Forty one patients (72%) underwent cervical ripening with Foley Catheter Balloon (FCB) only, eight (14%) with FCB and vaginal prostaglandins (VP), two (3.5%) with VP only and six patients (10.5%) did not require cervical ripening. One-third (33%) of patients stated, both before the commencement of cervical ripening and after delivery, that they would feel happy to undergo outpatient cervical ripening. Patient acceptance of outpatient cervical ripening has potential economic and psychosocial benefits for the healthcare system and patient respectively. PMID- 27188721 TI - A mononuclear nonheme cobalt(iii)-hydroperoxide complex with an amphoteric reactivity in electrophilic and nucleophilic oxidative reactions. AB - A mononuclear nonheme cobalt(iii)-hydroperoxide complex bearing a tetramethylated cyclam ligand, [(12-TMC)Co(III)(OOH)](2+), was synthesized and characterized spectroscopically and computationally; the cobalt(iii)-hydroperoxide complex exhibited an amphoteric reactivity in electrophilic and nucleophilic oxidative reactions. PMID- 27188720 TI - SOX7 co-regulates Wnt/beta-catenin signaling with Axin-2: both expressed at low levels in breast cancer. AB - SOX7 as a tumor suppressor belongs to the SOX F gene subfamily and is associated with a variety of human cancers, including breast cancer, but the mechanisms involved are largely unclear. In the current study, we investigated the interactions between SOX7 and AXIN2 in their co-regulation on the Wnt/beta catenin signal pathway, using clinical specimens and microarray gene expression data from the GEO database, for their roles in breast cancer. We compared the expression levels of SOX7 and other co-expressed genes in the Wnt/beta-catenin pathway and found that the expression of SOX7, SOX17 and SOX18 was all reduced significantly in the breast cancer tissues compared to normal controls. AXIN2 had the highest co-relativity with SOX7 in the Wnt/beta-catenin signaling pathway. Clinicopathological analysis demonstrated that the down-regulated SOX7 was significantly correlated with advanced stages and poorly differentiated breast cancers. Consistent with bioinformatics predictions, SOX7 was correlated positively with AXIN2 and negatively with beta-catenin, suggesting that SOX7 and AXIN2 might play important roles as co-regulators through the Wnt-beta-catenin pathway in the breast tissue to affect the carcinogenesis process. Our results also showed Smad7 as the target of SOX7 and AXIN2 in controlling breast cancer progression through the Wnt/beta-catenin signaling pathway. PMID- 27188722 TI - Discovery of ERBB3 inhibitors for non-small cell lung cancer (NSCLC) via virtual screening. AB - As a member of the epidermal growth factor receptor family (EGFR) of receptor tyrosine kinases, ERBB3 plays an important role in mediating cellular growth and differentiation. Recent research works identified that CD74-NRG1 fusions lead to overexpression of the EGF-like domain of NRG1, and thus activate ERBB3 and PI3K AKT signaling pathways. The fusion was detected in lung adenocarcinomas, and served as an important oncogenic factor for ERBB3 driven cancers. A sequential virtual screening strategy has been applied to ERBB3 crystal structure using databases of natural products and Chinese traditional medicine compounds, and led to identification of a group of small molecular compounds potentially capable of blocking ERBB3. Six small molecular compounds were selected for in vitro analysis. Five of these molecules significantly inhibited the growth of A549 cells. Among them, compound VS1 is the most promising one with IC50 values of 269.75 MUM, comparing to the positive control of nimustine hydrochloride with IC50 values of 264.14 MUM. With good specificity and predicted ADMET results, our results support the feasibility by using a pharmacophore of the compound VS1 for designing and optimization of ERBB3 inhibitors. PMID- 27188723 TI - Application of the quantum mechanical IEF/PCM-MST hydrophobic descriptors to selectivity in ligand binding. AB - We have recently reported the development and validation of quantum mechanical (QM)-based hydrophobic descriptors derived from the parametrized IEF/PCM-MST continuum solvation model for 3D-QSAR studies within the framework of the Hydrophobic Pharmacophore (HyPhar) method. In this study we explore the applicability of these descriptors to the analysis of selectivity fields. To this end, we have examined a series of 88 compounds with inhibitory activities against thrombin, trypsin and factor Xa, and the HyPhar results have been compared with 3D-QSAR models reported in the literature. The quantitative models obtained by combining the electrostatic and non-electrostatic components of the octanol/water partition coefficient yield results that compare well with the predictive potential of standard CoMFA and CoMSIA techniques. The results also highlight the potential of HyPhar descriptors to discriminate the selectivity of the compounds against thrombin, trypsin, and factor Xa. Moreover, the graphical representation of the hydrophobic maps provides a direct linkage with the pattern of interactions found in crystallographic structures. Overall, the results support the usefulness of the QM/MST-based hydrophobic descriptors as a complementary approach for disclosing structure-activity relationships in drug design and for gaining insight into the molecular determinants of ligand selectivity. Graphical Abstract Quantum Mechanical continuum solvation calculations performed with the IEF/PCM-MST method are used to derived atomic hydrophobic descriptors, which are then used to discriminate the selectivity of ligands against thrombin, trypsin and factor Xa. The descriptors provide complementary view to standard 3D-QSAR analysis, leading to a more comprehensive understanding of ligand recognition. PMID- 27188724 TI - Theoretical study of the structures and first hyperpolarizabilities of C60Cl n and Li@C60Cl n (n = 4, 6, 8, 10). AB - We recently reported (Song Y-D et al., 2016, J Mol Model 22:50) that doping with Li greatly affects the static first hyperpolarizability of C60Cl2. In this work, with a view to creating nonlinear optical materials with high thermodynamic stability and wide transparent regions, a series of Li@C60Cl n (n = 4, 6, 8, 10) were designed. The structures, electrostatic potentials, electronic structures, absorption spectra, and linear and nonlinear optical properties of C60Cl n and Li@C60Cl n were systematically investigated using density functional theory (DFT) methods. The results of our calculations indicated that the stability of these molecules decreases in the order Li@C60Cl10 > Li@C60Cl8 > Li@C60Cl6 > Li@C60Cl4. It is clear that the number of Cl atoms greatly influences the stability of Li@C60Cl n . Li@C60Cl n showed greater thermodynamic stability than Li@C60Cl2. We also investigated the first hyperpolarizabilities of Li@C60Cl n and found them to be 2973, 3640, 4307, and 2627 au for n = 4, 6, 8, and 10, respectively-higher than that of Li@C60Cl2. Finally, we noted that the transparent region could be modulated by increasing the number of Cl atoms: Li@C60Cl n possess wider transparent regions than that of Li@C60Cl2. We therefore believe that this study has highlighted an effective method for designing nonlinear optical materials with high thermodynamic stability and wide transparent regions. PMID- 27188725 TI - Thermal reaction of the ionic liquid 1,2-dimethyl-(3-aminoethyl) imidazolium tetrafluoroborate: a kinetic and theoretical study. AB - Since the thermal stabilities of ionic liquids (ILs) are of significance for their application, an amine-functionalized IL 1,2-dimethyl-(3-aminoethyl) imidazolium tetrafluoroborate [aEMMIM][BF4] was chosen to study thermal decomposition mechanisms via the methods of FT-IR, (1)H NMR, TGA, TGA-MS and density functional theory (DFT) calculations. Theoretical and experimental results indicated that amine-functionalization reduces the thermal stability of [aEMMIM][BF4] compared to its non-functionalized counterpart. Moreover, we found that [aEMMIM][BF4] follows a unimolecular nucleophilic substitution (SN1) decomposition (98.8 %), whereas the bimolecular nucleophilic substitution (SN2) decomposition (1.2 %) is unfavorable. The SN1 and SN2 reactions were fully optimized at B3LYP/6-311++G(d,p) level, and the energies of reactant (R), intermediates (IM), transition state (TS) and product (P) were obtained and analyzed by reaction mechanism. The energy of the intermediate is higher than that of the reactants by 18.92 kJ mol(-1), and the energy of the TS is higher than that of the IM by 155.23 kJ mol(-1). This result indicates that the IM are also more stable than the P2 product, thus the reaction is endothermic. The chemical nature of the covalent and hydrogen bonds was analyzed by vibrational modes analysis (VMA), nature bond orbital (NBO) and the theory of atoms in molecules (AIM). Graphical Abstract Proposed thermal decomposition of [aEMMIM][BF4] via unimolecular ( SN1) and bimolecular( SN2) nucleophilic substitution mechanisms. The electrostatic potential surface (ESP) of the transition state illustrates that hydrogen bonds are generated when [BF4](-) is close to [aEMMIM](+), and SN1 decomposition is much favorable than SN2 decomposition. PMID- 27188727 TI - Overexpression of X chromosome-linked inhibitor of apoptosis by inhibiting microRNA-24 protects periodontal ligament cells against hydrogen peroxide-induced cell apoptosis. AB - Hydrogen peroxide (H2O2), a common oral clinical drug for the tooth bleaching, induces severe cell apoptosis of periodontal ligament cells (PDLCs). The excessive cell apoptosis of PDLCs impairs periodontal tissue damage and repair. However, the underlying mechanism is incompletely understood. Here, we showed that microRNA-24 (miR-24) played an important role in regulating H2O2-induced cell apoptosis of PDLCs. We found that miR-24 expression was increased in PDLCs in response to H2O2 treatment. Down-regulation of miR-24 obviously rescued H2O2 induced cell apoptosis in PDLCs. By bioinformatic analysis, X chromosome-linked inhibitor of apoptosis (XIAP) was identified as a candidate target gene of miR 24, which was further verified by the dual-luciferase reporter assay. Furthermore, the protein expression level of phosphatase and tensin homolog deleted on chromosome ten was significantly decreased by miR-24 silencing, whereas the phosphorylation of Akt was remarkably increased by miR-24 silencing. In addition, the gene silencing of XIAP significantly reduced Akt activity and blocked the protective effect of the miR-24 inhibitor against H2O2-induced cell apoptosis. Overall, our findings suggest that miR-24 plays an important role in regulating the cell survival of PDLCs through targeting XIAP. PMID- 27188728 TI - Cell-free fetal DNA in amniotic fluid supernatant for prenatal diagnosis. AB - In widespread conviction, amniotic fluid is utilized for prenatal diagnosis. Amniotic fluid supernatant is usually discarded, notwithstanding being a good source of fetal DNA. The aim of the present study was to assess cell-free fetal DNA extracted from amniotic fluid supernatant for application in prenatal diagnosis such as gender determination and early diagnosis of beta-thalassemia. Samples of amniotic fluid of 70 pregnant women were collected and went through routine tests along with tests for cell-free fetal DNA from amniotic fluid supernatant. The DNA in the amniotic fluid supernatant was extracted and analyzed for gender determination by PCR and Real-time PCR. ARMS-PCR was applied to test early diagnosis of IVS II-I mutation (common beta-thalassemia mutation) and E7V mutation for sickle cell anemia using DNA extracted from the amniotic fluid supernatant. Using the cell-free fetal DNA extracted from the amniotic fluid supernatant, the sensitivity of PCR and Real-time PCR for gender detection was compared with the routine cytogenetic method. The fetus tested for sickle cell anemia and beta-thalassemia was observed to be healthy but heterozygous for IVS II-I mutation. The findings indicated that cell-free fetal DNA from amniotic fluid supernatant can be a good source of fetal DNA and be used in early prenatal diagnosis since because of its fast and accurate application. Therefore, it would be suggested that the amniotic fluid supernatant's disposal is prevented because if the tests needs to be repeated, cell-free fetal DNA extracted from the amniotic fluid supernatant can be used as an alternative source for prenatal diagnosis. PMID- 27188726 TI - G2013 modulates TLR4 signaling pathway in IRAK-1 and TARF-6 dependent and miR 146a independent manner. AB - Inflammation is inseparable part of different diseases especially cancer and autoimmunity. During inflammation process toll like receptor 4(TLR4) responds to lipopolysaccharide (LPS), one of the bacterial components, and TLR4 signaling leads to interleukine-1 receptor associated kinase-1 (IRAK1) and tumor necrosis factor (TNF) receptor associated factor6 (TRAF6) activation which ultimately results in nuclear factor- KB (NF-KB) activation as the main transcription factor of inflammatory cytokines. Conversely, NF-KB over activation induces miR-146a in innate immune cells which can consequently reduce TRAF6, IRAK1, and NF-KB activation in a negative feedback. G2013 is a novel designed non-steroidal anti inflammatory drug (NSAID) which was recently shown to be effective in experimental autoimmune encephalomyelitis (EAE) mouse model. The aim of this study was to evaluate G2013 effects on inflammatory (IRAK1 and TRAF6) and anti inflammatory (miR-146a) factors of TLR4 signaling pathway. For this purpose, cytotoxicity of G2013 has been evaluated by MTT assay. Expression level of miR 146a in PBMCs and IRAK1 along with TRAF6 in HEK-293 TLR4 cells have been determined using real time PCR. Our results showed that IC50 of G2013 was 25MUg/ml, thus 5 and 25 MUg/ml concentrations used for further treatments as low dose and high dose concentrations. Our results showed that IRAK1 expression reduced between 5 to 8 fold after treatment by G2013 in a dose dependent manner (p<0.001). In parallel TRAF6 expression declined between 3 to 10 fold dose dependently (p<0.05). However, miR-146a expression was not affected after treatment with low dose and high dose of G2013. In conclusion our data showed that G2013 can regulate TLR4 signaling pathway during inflammation by reducing downstream signaling molecules, IRAK1 and TRAF6 without altering miR-146a expression. PMID- 27188729 TI - Perfluorocarbon inhibits lipopolysaccharide-induced macrophage inflammatory protein-2 expression and activation of ATF-2 and c-Jun in A549 pulmonary epithelial cells. AB - The signaling pathway that mediates the anti-inflammatory effects of perfluorocarbon (PFC) in alveolar epithelial cells treated with lipopolysaccharide (LPS) remains unclear. To evaluate the role of macrophage inflammatory protein-2 (MIP-2), four A549 treatment groups were utilized: (1) untreated control, (2) 10 MUg/mL of LPS, (3) 10 MUg/mL of LPS+30% PFC and (4) 30% PFC. MIP-2 mRNA expression was determined by qPCR and ELISA. Mitogen-activated protein kinase (MAPK) activation was determined by Western blot analysis, and MIP 2 expression was determined by qPCR following treatment with MAPK inhibitors. PFC suppressed LPS-induced MIP-2 mRNA levels (P<=0.035) and MIP-2 secretion (P<=0.046). LPS induced ATF-2 and c-Jun phosphorylation, which was suppressed by PFC. Finally, inhibitors of ERK, JNK, and p38 suppressed LPS-induced MIP-2 mRNA expression. Thus, PFC inhibits LPS-induced MIP-2 expression and ATF-2 and c-Jun phosphorylation. To fully explore the therapeutic potential of PFC for acute lung injury (ALI), in vivo analyses are required to confirm these effects. PMID- 27188730 TI - The role of Iron on breast cancer stem-like cells. AB - Iron is a fundamental nutrient that enables the functions of vital enzymes involved in cell replication, metabolism and growth. Cancer cells contain higher systemic iron levels relative to normal cells. In breast cancer cells, human epidermal growth factor receptor 2 (HER2) is overexpressed more than 30% of normal and its poorly prognosis results in elevated the proportion of cancer stem cells (CSCs) which are the main drivers in cancer recurrence. Finding a relation between increases of iron levels, HER2 expression and CSC population may provide new tools for breast cancer therapy. In this study, therefore, iron dependency in HER2 overexpression and CSC survival is examined in breast cancer cell line, MCF7. It has shown that cells overexpressing HER2 require iron more than their vector counterparts and HER2-increased CSCs are vulnerable to iron chelation. Additionally, this sensitivity of CSCs to iron reduction is obviously indicated in various breast cancer cell lines; HCC1954, MDA-MB-435 and Hs578T. Finally, the concept is also shown in neoplastically transformed breast cancer cell line, HMLER. Altogether, this study demonstrates that iron depletion causes toxicity for CSCs. PMID- 27188731 TI - Detection of the novel IL-1 family cytokines by QAH-IL1F-1 assay in rheumatoid arthritis. AB - The interleukin (IL)-1 family of cytokines comprises 11 members, including 7 pro inflammatory cytokines (IL-1alpha, IL-1beta, IL-18, IL-33, IL-36alpha, IL 36beta,IL-36gamma) and 4 anti-inflammatory cytokines (IL-1R antagonist (IL-1Ra), IL-36Ra, IL-37 and IL-38), and play central roles in mediating immune responses. In this study, we detected serum levels of IL-36 subfamily cytokines (including IL-36alpha, IL-36beta, IL-36gamma, IL-36Ra and IL-38), IL-37, IL-33 and aimed to investigate the roles of these cytokines in rheumatoid arthritis (RA) preliminarily. A total of 10 RA patients and 10 healthy controls (HCs) were involved in this study, we measured IL-36 subfamily cytokines, IL-37 and IL-33 levels in the serum of the experiment subjects by QAH-IL1F-1 assay. Clinical and laboratory data of the subjects were collected and analyzed by Spearman's rank test. Compared to that of HCs, IL-36alpha, IL-36beta, IL-36Ra, IL-38 and IL-33 levels were significantly increased in RA patients. We also found RA patients with elevated IL-36Ra had a higher ESR and RF-IgM, and there was a positive correlation between increased IL-36alpha and CRP. Our study suggests that parts of the novel members of IL-1 family cytokines were involved in the pathogenesis of RA, and may provide a novel target for therapies of RA. PMID- 27188732 TI - Enhancing immune responses of EV71 VP1 DNA vaccine by co-inoculating plasmid IL 12 or GM-CSF expressing vector in mice. AB - Enterovirus 71 (EV71) is a major causative viral agent for large outbreaks of hand, foot, and mouth disease in children and infants, yet there is no vaccine or effective antiviral treatment for severe EV71 infection. The immunogenicity of EV71 VP1 DNA vaccine and the immunoregulatory activity of interleukin-12 (IL-12) or granulocyte-monocyte colony stimulating factor (GM-CSF) were investigated. DNA vaccine plasmids, pcDNA-VP1, pcDNA-IL-12 and pcDNA-GM-CSF were constructed and inoculated into BALB/c mice with or without pcDNA-IL-12 or pcDNA-GM-CSF by intramuscular injection. Cellular and humoral immune responses were assessed by indirect ELISA, lymphocyte proliferation assays, cytokine release assay and FACS. The VP1 DNA vaccine had good immunogenicity and can induce specific humoral and cellular immunity in BALB/c mice, while IL-2 or GM-CSF plays an immunoadjuvant role and enhances specific immune responses. This study provides a frame of reference for the design of DNA vaccines against EV71. PMID- 27188733 TI - The roles of SPBC409.08 and SPAC9.02c hypothetical genes in cell cycle and stress response, in Schizosaccharomyces pombe. AB - Polyamine molecules are known to have important roles in the cell cycle control and fighting against stress in the cell. The mechanism and modification of polyamines are regulated by the cooperation of many proteins such as polyamine transporter proteins and polyamine acetyltransferases. In this study, our aim is to characterize two hypothetical Schizosaccharomyces pombe genes, SPBC409.08 and SPAC9.02c, which show sequence similarity to spermine family transporters and polyamine N-acetyltransferases, respectively. To this end, we generated deletion mutants of SPBC409.08 and SPAC9.02c genes using Bahler method and checked the cell cycle progression and stress responses of these mutants. Our results showed that SPBC409.08Delta cells showed some defects in the cell size, while SPAC9.02cDelta cells showed some sensitivity to UV irradiation. These data support their potential roles in the cell cycle and stress response. To our knowledge our results are the first experimental characterization of these genes. PMID- 27188734 TI - Efficacy of hematopoietic stem cell formultiple sclerosis, an evidence based meta analysis. AB - Multiple sclerosis (MS) is thought to be a serious autoimmune disease. However, few therapy method was efficient for MS. The hematopoietic cell transplant (HCT) has been reported for a long time and can be used for MS. The clinical trials consisted of small samples and gave confusing results. This systematic review and meta-analysis aims to estimate the effects of HCT for adults with MS. We searched the database of CNKI, PUBMED, EMBASE, WEB of SCIENCE and the Cochrane Center Register of Controlled Trials to find initial studies and selected the appropriate researches included in the meta-analysis based on the inclusion and exclusion criteria. I2 was used to evaluate the heterogeneity and meta-regression was used for finding the source. Random effort model was performed to pool the data and funnel plot was drawn to determine publication bias. Six or eight single arm clinical trials studies were included. The I2 value was 0.77 and 0.93, suggesting a heavy heterogeneity between studies. However, meta-regression analysis did not find the source of heterogeneity in which the publication country and follow up time were the influencing factors. Compared with baseline, the EDSS score of MS patients after HCT has a statistical decrease of 0.62 (95% CI 0.14, 1.10) at the 12th month and 1.26 (95%CI: 0.38, 2.14) at the follow up time ending point respectively. Available evidence suggests some clinical benefits of HCT combined with immunotherapy on MS. Due to wide confidence intervals that are characteristics of small evidence bases, further investigations to provide enough baseline information according to the RCTs are needed for further analysis, such as subgroup analysis and meta-regression analysis. PMID- 27188735 TI - Genetic diversity of Iranian honey bee (Apis mellifera meda Skorikow, 1829) populations based on ISSR markers. AB - Honey bee is one of the most important insects considering its role in agriculture,ecology and economy as a whole. In this study, the genetic diversity of different Iranian honey bee populations was evaluated using inter simple sequence repeat (ISSR) markers. During May to September 2014, 108 young worker honey bees were collected from six different populations in 30 different geoclimatic locations from Golestan, Mazendaran, Guilan, West Azerbaijan, East Azerbaijan, Ardebil provinces of Iran. DNA was extracted from the worker honey bees. The quality and quantity of extracted DNA were measured. A set of ten primers were screened with the laboratory populations of honey bees. The number of fragments produced in the different honey bee populations varied from 3 to 10, varying within 150 to 1500 bp. The used ten ISSR primers generated 40 polymorphic fragments, and the average heterozygosity for each primer was 0.266. Maximum numbers of bands were recorded for primer A1. A dendrogram based on the Unweighted Pair Group Method with Arithmetic mean (UPGMA) method generated two sub-clusters. Honey bee populations of Golestan, Mazendaran, Guilan provinces were located in the first group. The second group included honey bee populations of Ardebil, West Azerbaijan, East Azerbaijan provinces, but this group showed a close relationship with other populations. The results showed obviously the ability of the ISSR marker technique to detect the genetic diversity among the honey bee populations. PMID- 27188737 TI - Effect of ketamine anesthesia on cognitive function and immune function in young rats. AB - The aim of the current study was to explore the effect of the ketamine on the immune function and cognitive function in young rats. The young rats (40) rats were randomly divided into two groups where each group contains 20 rats, such as Group I: normal control; Group II: Ketamine treated group. All group rats received the intravenous injection of treatment for three times and the hippocampal neuronal apoptosis and the immune parameters such as IL-2, IL-4 and IL-10 and whole brain IL-1beta level were estimated. The cognitive ability effect of the young rats was also tested using the Morris water maze test. In Morris water maze test, it has been found, as the time increases, the latency of the control group and ketamine treated groups rats were gradually decreased, with a significant difference. The latency rate of the control group was unchanged significantly (P<0.05), but after 3 days, the latency has been decreased significantly. The hippocampal neuronal apoptosis of the control group and ketamine treated group rats were found to be 13.5*5.8 % and (2.1*1.4) %, respectively. The level of the serum IL-4 and IL-10 were also found significantly (P<0.05) higher in the ketamine group as compared to the control group rats. The level of the IL-2 was found to be almost similar in both normal control and ketamine group rats. Markedly, the level of the whole brain IL-1beta was found to be significantly higher in the ketamine treated group in comparison to the control group rats. On the basis of the above fact, it has been conclude that the ketamine might be able to inhibit the cognitive function as well as immune function. PMID- 27188736 TI - Expression and significance of aquaporin protein in sprague-dawley rats after experimental intraventricular hemorrhage. AB - The AQP4 protein in Sprague-Dawley (SD) rats was expressed after experimental intraventricular hemorrhage to investigate the possible pathogenesis of chronic posthemorrhagic hydrocephalus. Seventy SD rats were randomly divided into two groups - sham-operated group (n=35) and experimental group (n=35). Saline and citrated autologous blood were injected into the lateral ventricle of the SD rats in the two groups, respectively. The rats in experimental group were further divided into seven subgroups based on different time points at 3 h, 6 h, 12 h, 1 d, 3 d, 5 d and 7 d. The change of expression of AQP4 protein at different time of bleeding were detected by immumohistochemical techniques and mRNA of AQP4 was observed by in situ hybridization. It was found that 75% rats in experimental group suffered from chronic hydrocephalus at 12 h after intraventricular hemorrhage. High protein expression of AQP4 was observed in the apical of cuboidal epithelium of choroids plexus. The protein expression of AQP4 gradually weakened in experimental group after 3 days of intraventricular hemorrhage and dropped to the minimum at the 7th day, which was significantly different from the control and operative groups (P<0.05). The mRNA expression of AQP4 was weaker than the protein expression, and the locations of expression were generally in agreement with each other. PMID- 27188739 TI - Expression and variability of lipid metabolism genes in intracranial aneurysm. AB - The objective of this study was to investigate the association between mRNA expression and single nucleotide polymorphisms (SNPs) of the ATP-binding cassette transporter (ABCA1) gene, apolipoprotein A1 (APOA1) gene, low-density lipoprotein (LDLR) gene and RNA gene located in the CDKN2B-CDKN2A cluster (CDKN2B-AS1) involved in lipid metabolism and the occurrence of intracranial aneurysm (IA). Fifty three IA patients, and 27 controls (IA-free) were enrolled in this study and were genotyped for seven single nucleotide polymorphisms. Increased expression of the LDLR gene in IA patients was observed. The A/G genotype and the A allele of the c. -113G>A polymorphism of the APOA1 gene were associated with increased occurrence of IA (ORs 12.36 and 14.14, respectively), while the G/G genotype and G allele showed the opposite tendency (ORs 0.06 and 0.07, respectively). We also detected that the A/A-G/A combined genotype of the c. 113G>A - APOA1 and g.46859A>G - LDLR SNPs was associated with a decreased occurrence of IA. Moreover, the A/G-G/G combined genotype of the c.656G>A - ABCA1 and c. -113G>A - APOA1 was associated with a decreased occurrence of IA. The results of our study suggest the association between expression and variability of lipid metabolism genes and occurrence of IA. PMID- 27188740 TI - Amyloid beta directed antibody for Alzheimer's disease, an evidence based meta analysis. AB - In several preclinical researches, antibody of Aacting directly in the central nervous system showed a great efficacy on the clearance of plaques. However, the other researches were opposite. We performed a meta-analysis to evaluate the amyloid-beta-directed antibody treatment of Alzheimer's disease. We searched Pubmed, Web of science, Embase and Cochrane library. Pooled data was calculated by standard mean difference. The heterogeneity and publication bias were evaluated by I2 and funnel plot. Totally, 5 RCTs (randomized clinical trials) with high qualities were included. There weas no difference of mean change form baseline between therapy and placebo group based on Mini-Mental State Examination (MMSE, SMD = 0.00, p = 0.97, 95% CI = -0.23 0.22) and Clinical Dementia Rating Sum of Boxes (CDR-SB, SMD = 0.22, p = 0.39, 95% CI = -0.28 0.71), but a significant decrease according to Alzheimer's Disease Assessment Scale (ADAS-cog, SMD = 0.07, p = 0.01, 95% CI = -0.02 0.13). In conclusion, Antibody was not benefit for AD based on MMSE and CDR-SB but had a little effect according to ADAS cog. PMID- 27188738 TI - Molecular and characterization of NnPPO cDNA from lotus (Nelumbo nucifera) in rhizome browning. AB - The complete cDNA (NnPPO) of polyphenol oxidase in Nelumbo nucifera was successfully isolated, using Rapid amplification cDNA end (RACE) assays. The full length cDNA of NnPPO was 2069 bp in size, containing a 1791 bp open reading frame coding 597 amino acids. The putative NnPPO possessed the conserved active sites and domains for PPO function. Phylogenetic analysis revealed that NnPPO shared high homology with PPO of high plants, and the homology modeling proved that NnPPO had the typical structure of PPO family. In order to characterize the role of NnPPO, Real-time PCR assay demonstrated that NnPPO mRNA was expressed in different tissues of N. nucifera including young leave, rhizome, flower, root and leafstalk, with the highest expression in rhizome. Patterns of NnPPO expression in rhizome illustrated its mRNA level was significantly elevated, which was consistent with the change of NnPPO activity during rhizome browning. Therefore, transcriptional activation of NnPPO was probably the main reason causing rhizome browning. PMID- 27188741 TI - Meta-analysis of traditional herbal medicine in the treatment of nonalcoholic fatty liver disease. AB - Traditional Chinese herbal medicine (TCM) has been found effective for nonalcoholic fatty liver disease (NAFLD) based on its unique theory system and substantial herb remedies. The aim of this meta-analysis was to evaluate the efficiency and safety of one of the TCM, Danshen in the treatment of NAFLD. Seven English and Chinese databases were searched from inceptions to December 2015. RCTs which compared Danshen with placebo in adult patients with NAFLD were included. Totally, 8 RCTs with a total of 800 patients were identified. The results showed that compared with placebo, Danshen had increased total effectiveness rate, lower level of ALT, AST, TC and TG, LDL and higher level of liver/spleen computed tomography ratio. The present meta-analysis suggests that Danshen may have positive effects on nonalcoholic fatty liver disease. Future multicenter large-sample randomized clinical trials are still needed to confirm the efficacy and safety of our study. PMID- 27188742 TI - In Vitro and in Vivo antioxidant activity of ethyl acetate extraction of purple rice. AB - The antioxidant activities of ethyl acetate extraction of purple rice (EAEPR) were evaluated by various methods in vitro and in vivo. In in vitro antioxidant assays, EAEPR was found to have strong 2, 2-diphenyl-1-picrylhydrazyl radical scavenging activity hydroxyl radical, reducing power and metal-ion chelating activity. In in vivo antioxidant assays, mice were administered with EAEPR via gavage for 42 consecutive days. As a result, administration of EAEPR significantly enhanced the activities of glutathione peroxidase in serums and livers of mice. EAEPR could improve the lipid status, especially total cholesterol and low-density lipoprotein cholesterol levels. In addition, total phenolic content of EAEPR was 188.21mg/g. The main phenolic compounds in EAEPR analyzed by ultra-high performance liquid chromatography tandem mass spectrometry were determined as ferulic acid and quercetin. The contents of ferulic acid and quercetin in EAEPR were 14.21mg/g and 35.28mg/g, respectively. The Nrf2 expression was significantly elevated after administration of EAEPR.These results suggested that EAEPR had potent antioxidant activity and could be explored as a novel natural antioxidant. PMID- 27188743 TI - Hsa-miRNA-31 regulates epithelial cell barrier function by inhibiting TNFSF15 expression. AB - Ulcerative colitis (UC) is characterized by epithelial barrier disruption and alterations in immune regulation but with the etiology unknown. MicroRNA-31 is the most consistent differentially expressed miRNA in ulcerative colitis tissue. The aim of this project is to study the important roles of miRNA-31 in regulation of intestinal epithelial barrier function. We found that expression of miRNA-31 is proportional to the proliferation of Caco2-BBE cells and overexpression of miRNA-31 can increase its trans-epithelial resistance (TER) by decreasing the transepithelial permeability. miRNA-31 can directly bind to the 3-UTR of TNFSF15, thereafter negatively regulating its expression in Caco2-BBE cells. BrdU and TUNEL analysis demonstrated that transfection of miRNA-31 stimulates proliferation or apoptosis-resistance. Taken together, these results revealed a novel mecha-nism underlying the regulation of epithelial barrier function by miRNA-31 during its regulation on proliferation of epithelial cells. PMID- 27188744 TI - The efficacy of high-intensity, focused ultrasound treatment for non-neoplastic epithelial disorders of the vulva. AB - Non-neoplastic epithelial disorders of the vulva (NNEDV) are common types of vulval lesions. Although corticosteroids represent a first-line treatment for NNEDV, concerns exist about the safety associated with long-term topical corticosteroid use. Recently, several clinical trials have identified high intensity focused ultrasound (HIFU) as a promising treatment modality for NNEDV. The aim of this multi-center, randomized, controlled clinical trial was to investigate the efficacy of HIFU therapy in women with NNEDV based on histological alterations. We enrolled patients who were clinically diagnosed with NNEDV. They were randomized into 2 treatment groups: 1) halcinonide for 3 months or 2) HIFU once. A total of 123 patients were biopsied both prior to and after the therapy, and 62 and 61 patients were assigned to the HIFU and halcinonide groups, respectively. The histological changes were then analyzed. After the treatments, the therapeutic effects were observed in both groups. Comparing the diagnosis and alterations in lichenoid and sclerotic patterns and in chronic inflammation, we found statistically significant differences. Furthermore, when compared with the halcinonide group, the HIFU group exhibited enhanced curative effects that were statistically significant (P = 0.039). Based on the histological evidence from this randomized, controlled trial, HIFU represents an effective method for the treatment of NNEDV. PMID- 27188745 TI - Edible bird's nest enhances antioxidant capacity and increases lifespan in Drosophila Melanogaster. AB - In this study, we aims to investigate the effects of edible bird's nest (EBN) on anti-aging efficacy. In order to investigate lifespan and mortality rate of flies, we treated flies with various doses of EBN. Besides, fecundity, water content and food are determined and heat-stress test is conducted after flies treating with different medium. Effects of EBN on total antioxidant activity (T AOC), super-oxide dismutase activity (SOD), catalase activity (CAT), and malondialdehyde (MDA) were examined in drosophila melanogaster. Results indicated that flies in EBN treated group illustrated significantly lower mortality rates and longer median and maximum lifespan compared to control group (P<0.05). The fecundity in EBN-treated group was increased compared to control group. SOD levels and CAT activity were significantly increased, and MDA levels decreased in EBN-treated group compared to control group (P<0.01). In conclusion, EBN can extend lifespan, decrease mortality rate and increase survival rate in heat stress test, and which can also promote SOD and CAT activity and reduce MDA levels. EBN is able to delay drosophila melanogaster aging, attributing to the increasing antioxidant enzyme activities and decreasing content of lipid peroxidation products in drosophila melanogaster. PMID- 27188746 TI - Icariin induces S-phase arrest and apoptosis in medulloblastoma cells. AB - Medulloblastoma is the most common type of malignant brain tumor in children. Despite a relatively high long-term survival rate, complications still represent great burden for the majority of patients receiving traditional therapy. Therefore, the development of new effective treatments and drugs is urgently needed. A cell counting kit-8 (CCK-8) and colony formation assay were used to evaluate medulloblastoma cell proliferation and colony formation, respectively. Cell cycles and apoptosis were assessed by flow cytometry. A western blot was performed to determine the levels of protein expression. Axenograft model of medulloblastoma was established to evaluate the in vivo anticancer effects of icariin. The CCK-8 assay showed that icariin decreased cell viability in a dose- and time-dependent manner. The colony formation assay indicated that icariin potently inhibited the colony formation ability of Daoy and D341 cells. Icariin induced proliferation inhibition may be due to S-phase arrest in medulloblastoma cells. In addition, icariin induced apoptosis in a dose-dependent manner, as shown by the results of annexin V/propidium iodide (PI) double staining and Hoechst 33342 staining. Icariin progressively inhibited tumor growth and induced apoptosis in a mouse model. Moreover, cell cycle regulators Cyclin A, CDK2, and Cyclin B1, and apoptosis-related proteins caspase-3, caspase-9, poly (ADP-ribose) polymerase (PARP), and Bcl-2 were modulated in response to treatment with icariin in vitro and in vivo. Our results suggest that icariin may exert anticancer effects. Thus, it is a promising drug for medulloblastoma treatment. PMID- 27188747 TI - Pfizer blocks sales of its drugs for executions. PMID- 27188748 TI - Superparamagnetic Properties of Hemozoin. AB - We report that hemozoin nanocrystals demonstrate superparamagnetic properties, with direct measurements of the synthetic hemozoin magnetization. The results show that the magnetic permeability constant varies from MU = 4585 (at -20 degrees C) to 3843 (+20 degrees C), with the values corresponding to a superparamagnetic system. Similar results were obtained from the analysis of the diffusion separation of natural hemozoin nanocrystals in the magnetic field gradient, with MU = 6783 exceeding the value obtained in direct measurements by the factor of 1.8. This difference is interpreted in terms of structural differences between the synthetic and natural hemozoin. The ab initio analysis of the hemozoin elementary cell showed that the Fe(3+) ion is in the high-spin state (S = 5/2), while the exchange interaction between Fe(3+) electron-spin states was much stronger than kBT at room temperature. Thus, the spin dynamics of the neighboring Fe(3+) ions are strongly correlated, lending support to the superparamagnetism. PMID- 27188749 TI - The first detection of species of Babesia Starcovici, 1893 in moose, Alces alces (Linnaeus), in Norway. AB - Babesiosis is an emerging zoonotic disease and various wildlife species are reservoir hosts for zoonotic species of Babesia Starcovici, 1893. The objective of the present study was to investigate the presence and prevalence of Babesia spp. in moose Alces alces (Linnaeus) in two regions of Norway. A total of 99 spleen samples were collected from animals of various ages from an area with the occurrence of the tick Ixodes ricinus (Linnaeus, 1758), and from an area where the ticks are known to be absent. Infection was detected by the amplification of different regions of the 18S rRNA gene by using two different PCR primer sets specific of Babesia. Babesia spp. were found in the spleen samples of four moose. All Babesia-infected animals were from an area where ticks occur, with an infection rate of 6% (4 of 70). Babesia-positive samples were obtained from a five-month old moose calf and three adults. Two Babesia species, Babesia capreoli (Enigk et Friedhoff, 1962) and a B. odocoilei-like, were identified. Co-infection with Anaplasma phagocytophilum was obtained in two animals. This is the first report of the occurrence of B. capreoli and B. odocoilei-like species in moose. PMID- 27188751 TI - Surgical teams' attitudes and opinions towards the safety of surgical procedures in public hospitals in the Brazilian Federal District. AB - BACKGROUND: According to the World Health Organization, the WHO surgical safety checklist can prevent complications, improve communication and contribute to postsurgical safety culture; hence, there is a need to investigate the attitudes and opinions of surgical teams regarding safety utilizing the WHO instrument. The aim of this study was to assess the attitudes and opinions towards surgical safety among operating room professionals in three public hospitals in the Brazilian Federal District. METHODS: A cross-sectional study was conducted with the use of a checklist based on the safety attitudes questionnaire-operating room, sent out during the pre- and post-intervention surveys of the WHO surgical safety checklist (period I and period II) between 2012 and 2014. RESULTS: About 470 professionals, mostly nurse technicians, responded to the questionnaire in both periods. Regarding the perception of safety and agreement about the collaboration of the operating team, a significant statistical improvement of the nursing staff and anesthesiologists was observed in the operating room after the checklist was implemented. After utilizing the checklist before each surgical procedure, concerns about patient safety and compliance with standards as well as rules and hand-washing practices in the operating room statistically improved after the post-intervention, especially by the nursing staff. The checklist was considered easy and quick to use by most respondents. They also believed that the checklist inclusion improved communication, reflecting significant differences. At least 90.0 % of respondents from each team agreed that the checklist helps prevent errors in the operating room. CONCLUSIONS: The study results showed progress in relation to the attitudes and opinions regarding surgical safety from operating teams in relation to the checklist response in the surveyed units. However, difficulties in its implementation are experienced, especially in relation to checklist use acceptance by the surgeons. New studies are needed to verify the sustainability of the surgical teams' changes in attitudes in the hospitals studied. PMID- 27188752 TI - Long-term disability and prognostic factors in polyneuropathy associated with anti-myelin-associated glycoprotein (MAG) antibodies. AB - AIM OF THE STUDY: Neuropathy associated with IgM monoclonal gammopathy (MGUS) represents distinctive clinical syndrome, characterized by male predominance, late age of onset, slow progression, predominantly sensory symptoms, deep sensory loss, ataxia, minor motor impairment. More than 50% of patients with neuropathy associated MGUS possess antibodies against myelin-associated glycoprotein (MAG). Purpose of our study was to assess effects on disease progression of demographic, clinical and neurophysiological variables in our large cohort of patients. MATERIALS AND METHODS: Forty-three Caucasians patients were followed every eight months for median duration time of 93 months. Extremity strength was assessed with Medical Research Council (MRC) Scale, disability with overall disability status scale (ODSS), modified Rankin Scale and sensory function with Inflammatory Neuropathy Cause and Treatment (INCAT) sensory scale (ISS). Statistical analyses were conducted with parametric or non-parametric measures as appropriate. Survival analysis was used to test predictive value of clinical, demographical and neurophysiological variables. Variance analysis was conducted to explain difference on MRC between patients and groups at different time from onset. RESULTS: Results showed that demyelinating pattern, older age and absence of treatment were significant risk factors for disability worsening. No other factors emerged as predictors including gender, ataxia and tremor at baseline, level of anti-MAG and IgM protein concentration in serum. Despite worsening of all outcome measures between first and last visit, quality of life (HRQol) judged by patients did not vary significantly. CONCLUSIONS: Our study provides evidence that electrophysiologic pattern, age of onset and absence of treatment are strong predictor of prognosis in anti-MAG polyneuropathy. PMID- 27188754 TI - Introduction to the Culture, Health & Sexuality Virtual Special Issue on sex, sexuality and sex work. AB - This article provides an editorial introduction to a virtual special issue on sex work and prostitution. It offers a brief history of sex work studies as published in the journal Culture, Health & Sexuality; reflects on the breadth and scope of papers the journal has published; considers the contribution of the journal's papers to the wellbeing and sexuality of people who sell sex; and envisions future areas of inquiry for sex work studies. As authors, we identify major themes within the journal's archive, including activism, agency, context, discourse, hazard, health, legalisation, love, place, power, race, relationships, stigma and vulnerabilities. In particular, we reflect on how HIV has created an environment in which issues of culture, health and sexuality have come to be disentangled from the moral agendas of earlier years. As a venue for the dissemination of a reinvigorated scholarship, Culture, Health & Sexuality provides a platform for a community of often like-minded, rigorous thinkers, to provide new and established perspectives, methods and voices and to present important developments in studies of sex, sexuality and sex work. PMID- 27188753 TI - Identifying microRNAs targeting Wnt/beta-catenin pathway in end-stage idiopathic pulmonary arterial hypertension. AB - MicroRNAs (miRNAs) play important roles in the pathogenesis of pulmonary arterial hypertension (PAH). However, the pathways targeted by miRNAs in PAH have not been systematically investigated. We aim to identify dysregulated miRNAs for patients with idiopathic PAH (IPAH). miRNA profiling was performed on lung tissue total RNA from eight IPAH patients and eight control subjects. Real-time quantitative RT-PCR (qRT-PCR) was used for validation of miRNA and mRNA expression levels in 14 IPAH patients and 14 control subjects. Pathway enrichment analysis showed that Wnt/beta-catenin signaling is among the top PAH-related pathways enriched in target genes of dysregulated miRNAs. We confirmed the significant increased expression levels of five miRNAs (let-7a-5p, miR-26b-5p, miR-27b-3p, miR-199a-3p and miR-656) targeting major PAH-related pathways. Moreover, qRT-PCR validation of Wnt/beta-catenin pathway activation indicated multiple genes including receptors (FZD4, FZD5), core molecule (CTNNB1), and downstream targets (CCND1, VEGFA, and AXIN2) were significantly upregulated. The expression level of miR 199b-5p was positively correlated with patients' hemodynamics (PVR: r = 0.522, p = 0.038) and pulmonary vascular remodeling (muscularization: r = 0.540, p = 0.021). We confirmed overexpression of miR-199b-5p in hypoxic pulmonary arterial endothelial cells that negatively regulates GSK3B expression. In summary, miRNAs influence the pathogenesis of PAH by regulating major PAH-related pathways including Wnt/beta-catenin in end-stage IPAH. KEY MESSAGE: It is the first miRNA profiling study in lung tissue from end-stage idiopathic PAH. We identified dysregulated miRNAs and major pathways (e.g., Wnt signaling) in IPAH. Levels of miRNA expression were correlated with hemodynamics and pathological changes. We observed aberrant expression of target genes in the Wnt/beta-catenin pathway. miRNAs influence the pathogenesis of PAH by regulating major PAH-related pathways. PMID- 27188756 TI - A simple solution for antibody signal enhancement in immunofluorescence and triple immunogold assays. AB - Immunolocalization techniques are standard in biomedical research. Tissue fixation with aldehydes and cell membrane permeabilization with detergents can distort the specific binding of antibodies to their high affinity epitopes. In immunofluorescence protocols, it is desirable to quench the sample's autofluorescence without reduction of the antibody-dependent signal. Here we show that adding glycine to the blocking buffer and diluting the antibodies in a phosphate saline solution containing glycine, Triton X-100, Tween20 and hydrogen peroxide increase the specific antibody signal in tissue immunofluorescence and immunogold electron microscopy. This defined antibody signal enhancer (ASE) solution gives similar results to the commercially available Pierce Immunostain Enhancer (PIE). Furthermore, prolonged tissue incubation in resin and fixative and application of ASE or PIE are described in an improved protocol for triple immunogold electron microscopy that is used to show co-localization of GABA-A rho2 and dopamine D2 receptors in GFAP-positive astrocytes in the mouse striatum. The addition of glycine, Triton X-100, Tween20 and hydrogen peroxide during antibody incubation steps is recommended in immunohistochemistry methods. PMID- 27188757 TI - Aluminum resistance in wheat involves maintenance of leaf Ca(2+) and Mg(2+) content, decreased lipid peroxidation and Al accumulation, and low photosystem II excitation pressure. AB - The phytotoxic aluminum species (Al(3+)) is considered as the primary factor limiting crop productivity in over 40 % of world's arable land that is acidic. We evaluated the responses of two wheat cultivars (Triticum aestivum L.) with differential Al resistance, cv. Yecora E (Al-resistant) and cv. Dio (Al sensitive), exposed to 0, 37, 74 and 148 MUM Al for 14 days in hydroponic culture at pH 4.5. With increasing Al concentration, leaf Ca(2+) and Mg(2+) content decreased, as well as the effective quantum yield of photosystem II (PSII) photochemistry (Phi PSII ), while a gradual increase in leaf membrane lipid peroxidation, Al accumulation, photoinhibition (estimated as F v /F m ), and PSII excitation pressure (1 - q p ) occurred. However, the Al-resistant cultivar with lower Al accumulation, retained larger concentrations of Ca(2+) and Mg(2+) in the leaves and kept a larger fraction of the PSII reaction centres (RCs) in an open configuration, i.e. a higher ratio of oxidized to reduced quinone A (QA), than plants of the Al-sensitive cultivar. Four times higher Al concentration in the nutrient solution was required for Al-resistant plants (148 MUM Al) than for Al sensitive (37 MUM Al), in order to establish the same closed RCs. Yet, the decline in photosynthetic efficiency in the cultivar Dio was not only due to closure of PSII RCs but also to a decrease in the quantum yield of the open RCs. We suggest that Al(3+) toxicity may be mediated by nutrient deficiency and oxidative stress, and that Al-resistance of the wheat cultivar Yecora E, may be due at least partially, from the decreased Al accumulation that resulted to decreased reactive oxygen species (ROS) formation. However, under equal internal Al accumulation (exposure Al concentration: Dio 74 MUM, Yecora E 148 MUM) that resulted to the same oxidative stress, the reduced PSII excitation pressure and the better PSII functioning of the Al-resistant cultivar was probably due to the larger concentrations of Ca(2+) and Mg(2+) in the leaves. We propose that the different sensitivities of wheat cultivars to Al(3+) toxicity can be correlated to differences in the redox state of QA. Thus, chlorophyll fluorescence measurements can be a promising tool for rapid screening of Al resistance in wheat cultivars. PMID- 27188755 TI - Clopidogrel treatment may associate with worsening of endothelial function and development of new digital ulcers in patients with systemic sclerosis: results from an open label, proof of concept study. AB - BACKGROUND: Activated platelets release serotonin that binds 5-HT2B receptor on fibroblasts leading to fibroblast activation. Clopidogrel, an inhibitor of ADP dependent platelet activation prevents fibrosis in animal models of systemic sclerosis (SSc). We aimed at assessing whether i) ADP-dependent platelet activation is increased in patients with SSc compared to healthy subjects and patients with rheumatoid arthritis (RA) and ii) whether clopidogrel can effectively suppress ADP-dependent activation, reduce circulating serotonin levels and hence, favorably affect fibrosis or vasculopathy in patients with systemic sclerosis. METHODS: Thirteen patients with SSc were recruited. Platelet activation was assessed by aggregometry prior to and following 14 days of clopidogrel treatment. At the same time points serotonin and soluble vascular cell adhesion molecule 1 (s-VCAM1), a marker of endothelial dysfunction, were measured. RESULTS: ADP-dependent platelet activation was similar between patients with SSc (n = 13), patients with RA (n = 28) and healthy subjects (n = 22) (mean +/- SEM AU*min: 392.1 +/- 58.4, 535.5 +/- 61.33 and 570.9 +/- 42.9 in patients with SSc, patients with RA and healthy subjects respectively, p = 0.14). Clopidogrel treatment significantly reduced platelet activation in patients with SSc (mean +/- SEM AU*min: 392.1 +/- 58.4 vs 163.8 +/- 51.7, p = 0.014). Clopidogrel treatment did not affect serotonin levels but led to a significant increase in s-VCAM1 (p = 0.03). Three patients developed new digital ulcers during the study. The potential association of the study drug with the development of new digital ulcers led to early termination of the study. CONCLUSION: Clopidogrel may worsen markers of endothelial function and associate with development of new digital ulcers in patients with SSc. CLINICAL TRIAL REGISTRATION: ISRCTN63206606 . Registered 02/Dec/2014. PMID- 27188759 TI - Utilization of Patient Electronic Messaging to Promote Advance Care Planning in the Primary Care Setting. AB - BACKGROUND: Advance care planning (ACP) is an instrumental mechanism aimed at preserving patient autonomy. Numerous interventions have been proposed to facilitate the implementation of ACP; however, rates of completed advance directives (ADs) are universally low. Patient electronic portal messaging is a newer tool in patient-provider communication which has not been studied as a method to promote ACP. In this study, we hypothesized that the use of ACP specific patient electronic messages would increase rates of AD completion in patients aged 65 years and older in an academic primary care practice. METHODS: All primary care patients, aged 65+, who had previously enrolled in a patient electronic messaging system, within an academic primary care practice, were included for randomization. Two hundred patients were randomized to receive an electronic message. The primary outcome was the proportion of patients in each group who completed an AD, 3 months after intervention. Secondary outcomes included clinical utility of the completed ADs and proportion of patients who viewed their electronic messages. RESULTS: The intervention group completed an AD 5.5% of the time when compared to 2% in the control group (odds ratio 3.2 [1.6 6.3]). Up to 74.5% of patients opened their electronic messages. CONCLUSION: Among primary care patients aged 65 years and older, use of AD-specific electronic messaging statistically significantly increased the rate of AD completion, but the absolute number of completed AD remained relatively low. These data suggest that this valuable communication tool holds opportunities for further improvement. Older, frailer adults were more likely to complete an AD, and prompted directives were more likely to include a written expression of the individual's health-care values and preference. PMID- 27188758 TI - Nurse Knowledge, Work Environment, and Turnover in Highly Specialized Pediatric End-of-Life Care. AB - OBJECTIVE: To examine the relationship between nurse knowledge, work environment, and registered nurse (RN) turnover in perinatal hospice and palliative care organizations. METHODS: Using nurse intellectual capital theory, a multivariate analysis was conducted with 2007 National Home and Hospice Care Survey data. RESULTS: Perinatal hospice and palliative care organizations experienced a 5% turnover rate. The professional experience of advanced practice nurses (APNs) was significantly related to turnover among RNs (beta = -.032, P < .05). Compared to organizations with no APNs professional experience, clinical nurse specialists and nurse practitioners significantly reduced RN turnover by 3 percentage points. No other nurse knowledge or work environment variables were associated with RN turnover. Several of the control variables were also associated with RN turnover in the study; Organizations serving micropolitan (beta = -.041, P < .05) and rural areas (beta = -.037, P < .05) had lower RN turnover compared to urban areas. Organizations with a technology climate where nurses used electronic medical records had a higher turnover rate than those without (beta = .036, P < .05). CONCLUSION: The findings revealed that advanced professional experience in the form of APNs was associated with reductions in RN turnover. This suggests that having a clinical nurse specialist or nurse practitioner on staff may provide knowledge and experience to other RNs, creating stability within the organization. PMID- 27188760 TI - Transitions to End-of-Life Care for Patients With Chronic Critical Illness: A Meta-Synthesis. AB - BACKGROUND: Adults with chronic critical illness (CCI) frequently experience a terminal trajectory but receive varying degrees of palliation and end-of-life care (EOLC) in intensive care units (ICUs). Why palliation (over curative treatment) is not augmented earlier for patients with CCI in ICU is not well understood. PURPOSE: To identify the social structures that contribute to timely, context-dependent decisions for transition from acute care to EOLC for patients with CCI and their families. METHODS: We conducted a meta-synthesis of qualitative and/or mixed-method studies that recruited adults with CCI, their families or close friends, and/or health-care providers (HCPs) in an ICU environment. RESULTS: Five studies reported data from 83 patients, 109 family members, and 57 HCPs across 5 institutions in Canada and the United States. Overall, we found that morally ambiguous social expectations of treatment tended to lock in HCPs to focus on prescriptive work of preserving life, despite pathways that could "open" access to augmenting palliation and EOLC. This process limited space for families' reflexivity and reappraisal of CCI as a phase liminal to active dying. Notably, EOLC mechanisms were informal and less visible. CONCLUSION: The management of dying is one of the central tenets of ICU care. Our findings suggest that patients and families need help in negotiating meanings of this situation and in using mechanisms that allow reappraisal and permit understanding of CCI as a phase liminal to dying. Moreover, these mechanisms may paradoxically reduce the ambiguity of patients' future, allowing them to live more fully in the present. PMID- 27188761 TI - Functionalized Nanolipobubbles Embedded Within a Nanocomposite Hydrogel: a Molecular Bio-imaging and Biomechanical Analysis of the System. AB - The purpose of this study was to explore the use of molecular bio-imaging systems and biomechanical dynamics to elucidate the fate of a nanocomposite hydrogel system prepared by merging FITC-labeled nanolipobubbles within a cross-linked hydrogel network. The nanocomposite hydrogel system was characterized by size distribution analysis and zeta potential as well as shears thinning behavior, elastic modulus (G'), viscous loss moduli (G"), TEM, and FTIR. In addition, molecular bio-imaging via Vevo ultrasound and Cell-viZio techniques evaluated the stability and distribution of the nanolipobubbles within the cross-linked hydrogel. FITC-labeled and functionalized nanolipobubbles had particle sizes between 135 and 158 nm (PdI = 0.129 and 0.190) and a zeta potential of -34 mV. TEM and ultrasound imaging revealed the uniformity and dimensional stability of the functionalized nanolipobubbles pre- and post-embedment into the cross-linked hydrogel. Biomechanical characterization of the hydrogel by shear thinning behavior was governed by the polymer concentration and the cross-linker, glutaraldehyde. Ultrasound analysis and Cell-viZio bio-imaging were highly suitable to visualize the fluorescent image-guided nanolipobubbles and their morphology post-embedment into the hydrogel to form the NanoComposite system. Since the nanocomposite is intended for targeted treatment of neurodegenerative disorders, the distribution of the functionalized nanolipobubbles into PC12 neuronal cells was also ascertained via confocal microscopy. Results demonstrated effective release and localization of the nanolipobubbles within PC12 neuronal cells. The molecular structure of the synthetic surface peptide remained intact for an extended period to ensure potency for targeted delivery from the hydrogel ex vivo. These findings provide further insight into the properties of nanocomposite hydrogels for specialized drug delivery. PMID- 27188763 TI - Controllable Eu valence for photoluminescence tuning in apatite-typed phosphors by the cation cosubstitution effect. AB - By cosubstituting [Ca(2+)-P(5+)] for [La(3+)-Si(4+)] in the Eu-doped Ca(2->8)La(8 >2)(SiO4)6-x(PO4)xO2 (0 <= x <= 6) system, Eu(3+) ions are controllably and gradually transformed to Eu(2+). Thus, the emission colors consecutively changed from red to blue/green light. Furthermore, excellent warm-white lights with the low correlated color temperature (CCT) range of 3500-3800 K and a high color rendering index (Ra) (88.4-93.2) have been achieved by mixing the as-prepared phosphors at different cation cosubstitution ratios. PMID- 27188764 TI - A comprehensive picture of the ultrafast excited-state dynamics of retinal. AB - All-trans retinal is the chromophore of microbial rhodopsins initiating energy conversion and cellular signalling by subpicosecond photoinduced switching. Here, we provide detailed UV-Vis transient absorption experiments to disentangle the complex photochemistry of this polyene, which is governed by its terminal aldehyde group. After photoexcitation to the S2((1)Bu(+)) state, the system exhibits polarity-dependent branching, populating separate S1((1)Ag(-)) and intramolecular charge transfer (ICT) species. In all solvents, population of a singlet npi* state from S1 is observed which represents the precursor of the T1 triplet state. While triplet formation dominates in nonpolar solvents (67% quantum yield), it is dramatically reduced in polar solvents (4%). The channel closes completely upon replacing the aldehyde by a carboxyl group, due to an energetic up-shift of (1)npi*. In that case, internal conversion via the ICT species becomes the main pathway, with preferential formation of the initially excited isomer. PMID- 27188762 TI - Displacement and HIV: Factors Influencing Antiretroviral Therapy Use by Ethnic Shan Migrants in Northern Thailand. AB - Migrant populations face increased HIV vulnerabilities, including limited access to antiretroviral therapy. Civil conflict in Myanmar has displaced thousands of people from the minority Shan ethnic group into northern Thailand, where they bear a disproportionate HIV burden. To identify barriers and facilitators of antiretroviral therapy use in this population, we conducted a rapid ethnographic assessment and case study with a clinical sample of Shan migrants receiving treatment for HIV in a district hospital in Chiang Mai, Thailand, Thai nurses providing their care, and health care administrators (n = 23). Barriers included fears of arrest and deportation, communication difficulties, perceived social marginalization, limited HIV knowledge, and lack of finances. Facilitating factors included hospital-based migrant registration services and community outreach efforts involving support group mobilization, referral practices, and radio broadcasts. These findings provided a contextualized account to inform policies, community interventions, and nursing practice to increase treatment access for minority migrant groups. PMID- 27188765 TI - Clinical Investigation of Matrix Metalloproteinases, Tissue Inhibitors of Matrix Metalloproteinases, and Matrix Metalloproteinase/Tissue Inhibitors of Matrix Metalloproteinase Complexes and Their Networks in Apical Periodontitis. AB - INTRODUCTION: This clinical study investigated the levels of metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) and respective forms (MMP/TIMP complexes) in apical periodontitis to determine their networks in the development of clinical/radiographic features, thus quantifying the levels of endotoxins (lipopolysaccharides) present in primarily infected root canals with apical periodontitis. METHODS: Twenty primarily infected root canals with apical periodontitis were selected. The presence of pain on palpation, tenderness to percussion, and the size of the radiographic lesion were recorded. The levels of MMPs (MMP-1, -2, and -9), TIMPs (TIMP-1 and -2), and their MMP/TIMP complexes (MMP-1/TIMP-1, MMP-1/TIMP-2, MMP-2/TIMP-1, MMP-2/TIMP-2, MMP9/TIMP-1, and MMP 9/TIMP-2) present in the periapical interstitial fluid were measured using the enzyme-linked immunosorbent assay. The kinetic chromogenic LAL test was used to quantify endotoxins. RESULTS: A higher mean level of MMP-9 (968.35 +/- 342.00 pg/mL) was followed by MMP-2 (894.00 +/- 591.62 pg/mL) and MMP-1 (789.43 +/- 342.83 pg/mL). The linear regression analysis revealed a positive association of MMP-1 with both MMP-2 and MMP-9 (all P < .001). TIMP-1 (481.79 +/- 86.09 pg/mL) (24/24) was found in higher levels than TIMP-2 (206.45 +/- 86.09 pg/mL) (P < .05), including a positive correlation of MMP-1 with both TIMP-1 and TIMP-2 (all P < .05). Higher mean levels of MMP1, -2, and -9 were found in teeth with larger size radiolucent lesions (>7 mm) compared with smaller ones (<=7 mm) (all P < .01). Higher levels of MMP-1 decreased the chance of TTP, whereas MMP-9 (odds ratio = 0.97) increased the chance of pain on percussion (odds ratio = 1.01). Higher levels of endotoxins present in root canals were positively correlated with larger amounts of MMP -9 (P < .05). CONCLUSIONS: MMPs, TIMPs, and their complexes (MMP/TIMP) are involved in apical periodontitis by interacting with complex networks in the development of clinical features and the severity of bone destruction. PMID- 27188766 TI - Urinary metabolomic profiling of asthmatics can be related to clinical characteristics. AB - Metabolomics has been increasingly explored to achieve an improved understanding of asthma. In the current observational and exploratory study, the first to have examined the relationship between oxidative stress extension, eosinophilic inflammation, and disease severity in asthmatic patients, metabolomics (using target aliphatic aldehydes and alkanes) was carried out using solid-phase microextraction (SPME) followed by a comprehensive two-dimensional gas chromatography coupled to mass spectrometry with a high-resolution time-of-flight analyzer (GC*GC-ToFMS). We were able to demonstrate that metabolomics can give valuable insights into asthma mechanisms once lipidic peroxidation assessed by urinary metabolomics is related to the clinical characteristics of nonobese asthmatics, such as disease severity, lung function, and eosinophilic inflammation. Nevertheless, considering our sample size, the obtained results require further validation using a much larger sample cohort. PMID- 27188768 TI - Veterinary Dermatology in Brazil. PMID- 27188769 TI - Canine atopic dermatitis: breed risk in Australia and evidence for a susceptible clade. AB - BACKGROUND: Genetic studies on canine atopic dermatitis (CAD) indicate that large populations from one geographical location are preferred for the identification of relevant susceptibility genes. Australian dogs are relatively isolated; studies on CAD in this population are limited. HYPOTHESIS/OBJECTIVES: To identify breeds at risk in the Australian dog population and to compare with worldwide breed predisposition. ANIMALS: Case records (n = 23,000) from University Veterinary Teaching Hospital (UVTH) dogs, including 722 with CAD. METHODS: The breed proportion of CAD and odds risk (OR) were calculated. A systematic review of 13 previous studies (1971-2010) was performed and compared to the study results by implementing an atopic dermatitis (AD)-to-reference population ratio (ADRPR). RESULTS: Eleven dog breeds with significant increased OR (>=1.0) were identified; all with breed CAD cases proportionally higher than their base hospital population. Gender risk in males from the pug dog breed (P = 0.007) was detected and the bichon frise breed had a similar trend (P = 0.05). Sixteen predisposed dog breeds were identified by systematic review. All breeds with significant increased OR in UVTH had ADRPR > 1.4; five (boxer, bulldog, Labrador retriever, pug, West Highland white terrier) were recognized as predisposed worldwide. One clade of breeds with common ancestry was highly represented in CAD cases worldwide and in Australia (81% of the significant OR cases). CONCLUSION AND CLINICAL IMPORTANCE: The use of a large population from one geographical location and ADRPR provided an objective comparison between worldwide AD studies; it identified one common clade of susceptible breeds. Breed genetics and related clinical presentation may help CAD diagnosis and treatment. PMID- 27188767 TI - Conservative fluid management prevents age-associated ventilator induced mortality. AB - BACKGROUND: Approximately 800 thousand patients require mechanical ventilation in the United States annually with an in-hospital mortality rate of over 30%. The majority of patients requiring mechanical ventilation are over the age of 65 and advanced age is known to increase the severity of ventilator-induced lung injury (VILI) and in-hospital mortality rates. However, the mechanisms which predispose aging ventilator patients to increased mortality rates are not fully understood. Ventilation with conservative fluid management decreases mortality rates in acute respiratory distress patients, but to date there has been no investigation of the effect of conservative fluid management on VILI and ventilator associated mortality rates. We hypothesized that age-associated increases in susceptibility and incidence of pulmonary edema strongly promote age-related increases in ventilator associated mortality. METHODS: 2month old and 20month old male C57BL6 mice were mechanically ventilated with either high tidal volume (HVT) or low tidal volume (LVT) for up to 4h with either liberal or conservative fluid support. During ventilation, lung compliance, total lung capacity, and hysteresis curves were quantified. Following ventilation, bronchoalveolar lavage fluid was analyzed for total protein content and inflammatory cell infiltration. Wet to dry ratios were used to directly measure edema in excised lungs. Lung histology was performed to quantify alveolar barrier damage/destruction. Age matched non ventilated mice were used as controls. RESULTS: At 4h, both advanced age and HVT ventilation significantly increased markers of inflammation and injury, degraded pulmonary mechanics, and decreased survival rates. Conservative fluid support significantly diminished pulmonary edema and improved pulmonary mechanics by 1h in advanced age HVT subjects. In 4h ventilations, conservative fluid support significantly diminished pulmonary edema, improved lung mechanics, and resulted in significantly lower mortality rates in older subjects. CONCLUSION: Our study demonstrates that conservative fluid alone can attenuate the age associated increase in ventilator associated mortality. PMID- 27188771 TI - Investigation and treatment of ovine psoroptic otoacariasis. AB - BACKGROUND: Psoroptic otoacariasis has been described worldwide and is caused by a mite morphologically indistinguishable from the sheep scab mite Psoroptes ovis. A single treatment of affected sheep with 200 MUg/kg of injectable ivermectin is reported to be curative. CASE REPORT: Psoroptes mites were isolated following treatment with ivermectin, but treatment with moxidectin at 1 mg/kg caused complete cessation of clinical signs. Affected animals were seropositive to Pso o 2 antigen enzyme-linked immunosorbent assay (ELISA) and had serum haptoglobin concentrations that overlapped with those described for field infections of classical sheep scab. CONCLUSIONS AND CLINICAL IMPORTANCE: Psoroptic otoacariasis is not controlled by single treatments of injectable ivermectin but resolves after a single treatment with injectable moxidectin. Pso o 2 ELISA can detect infection with Psoroptes spp. mites but cannot distinguish between sheep scab and psoroptic otoacariasis. PMID- 27188770 TI - Carriage of meticillin-resistant staphylococci between humans and animals on a small farm. AB - BACKGROUND: Meticillin-resistant staphylococci (MRS) are pathogens of increasing importance to human and animal health worldwide. Transmission of meticillin resistant Staphylococcus aureus (MRSA) between animals and humans has been well documented. By contrast, information about transmission of other Staphylococcus spp. is limited. HYPOTHESIS/OBJECTIVES: The aim of this study was to screen animals and humans on a small farm for nasal carriage of MRS and to assess interspecies exchange. METHODS: After detection of MRSA in a lung sample of a deceased cat, which lived on a small mixed farm, nasal swabs were taken within two weeks, four and 16 months from other animals of various species and humans living on the farm. Swabs were cultured for MRS which were then characterized molecularly. RESULTS: MRSA and meticillin-resistant coagulase negative staphylococci (MRCoNS), including Staphylococcus haemolyticus, S. epidermidis and S. fleurettii, were isolated from humans and different animal species. Typing of the MRS revealed isolates with the same characteristics in different human and animal hosts. CONCLUSIONS AND CLINICAL IMPORTANCE: To the best of the authors' knowledge, this is the first report of carriage of both MRSA and MRCoNS among humans and various animals within a shared environment. The detection of strains with indistinguishable molecular characteristics strongly suggested transmission of these MRS between the various animal species and humans. PMID- 27188772 TI - Initial characterization of stiff skin-like syndrome in West Highland white terriers. AB - BACKGROUND: Stiff skin syndrome and systemic or localized scleroderma are cutaneous disorders characterized by dermal fibrosis and present clinically with induration of the skin, with or without joint, internal organ or vascular involvement. OBJECTIVES: To provide clinical, histological and preliminary genetic analysis of two West Highland white terrier siblings presenting with indurated skin resembling stiff skin syndrome in humans. ANIMALS: Two client owned full sibling West Highland white terriers from two different litters. METHODS: Clinical examination, histopathological examination and whole genome sequencing analysis of affected and unaffected West Highland white terriers. RESULTS: Affected dogs exhibited markedly indurated skin that was attached firmly to the underlying tissue and incomplete closure of the mouth and eyes. No abnormalities were found by neurological or orthopaedic examination, radiographs of the head or whole body computed tomography. Histologically, the dermis and pannicular septa were thickened by a marked increase in coarse collagen fibres and a mild to moderate increase in collagen fibre diameter. The syndrome most likely follows an autosomal recessive mode of inheritance. The sequence analysis did not reveal any obvious causative variant in the investigated candidate genes ADAMTSL2 and FBN1. CONCLUSION AND CLINICAL IMPORTANCE: The clinical phenotype and histopathological features of two West Highland white terrier siblings resembled stiff skin syndrome in humans. Unlike in humans, or previously described beagles with stiff skin, there was no restriction of joint mobility. Genetic analysis did not detect a candidate causative variant and warrants further research. PMID- 27188773 TI - Bowenoid in situ carcinomas in two Devon Rex cats: evidence of unusually aggressive neoplasm behaviour in this breed and detection of papillomaviral gene expression in primary and metastatic lesions. AB - BACKGROUND: Bowenoid in situ carcinomas (BISCs) are rare feline tumours that are thought to be caused by papillomavirus infection. Although they usually develop in old cats and are slowly progressive, multiple aggressive BISCs have been reported previously in a comparatively young Devon Rex cat. ANIMALS: A 5-year-old (Case 1) and an 8-year-old (Case 2) Devon Rex cat developed numerous BISCs. Rapid progression resulted in euthanasia of both cats after 8 months. A postmortem examination was possible only for Case 2 and revealed pulmonary metastases. METHODS AND RESULTS: Consensus PCR amplified only Felis catus papillomavirus type 2 (FcaPV-2) DNA from lesions from both cats. High FcaPV-2 copy number and FcaPV-2 E6/E7 gene expression were detected in a BISC from Case 1. High FcaPV-2 copy number and FcaPV-2 gene expression were detected in a BISC, a cutaneous squamous cell carcinoma (SCC) and the pulmonary metastases from Case 2, but not in two other cutaneous SCCs. CONCLUSIONS: The results provide additional evidence that BISCs develop at a younger age in Devon Rex cats and that BISCs in Devon Rex cats have a more aggressive behaviour than BISCs in other cat breeds. These unusual features should be considered when evaluating and treating skin disease in Devon Rex cats. The detection of FcaPV-2 gene expression in the lung neoplasms suggests a potential role of FcaPV-2 in the development of metastatic disease. However, the absence of FcaPV-2 gene expression in two cutaneous SCCs suggests that other factors could have also promoted cancer development. PMID- 27188774 TI - 8p11 Myeloproliferative Syndrome with t(7;8) Translocation Presenting as Acute Myeloid Leukemia: A Case Report and Literature Review. PMID- 27188775 TI - Microbial inoculation of seed for improved crop performance: issues and opportunities. AB - There is increasing interest in the use of beneficial microorganisms as alternatives to chemical pesticides and synthetic fertilisers in agricultural production. Application of beneficial microorganisms to seeds is an efficient mechanism for placement of microbial inocula into soil where they will be well positioned to colonise seedling roots and protect against soil-borne diseases and pests. However, despite the long history of inoculation of legume seeds with Rhizobia spp. and clear laboratory demonstration of the ability of a wide range of other beneficial microorganisms to improve crop performance, there are still very few commercially available microbial seed inoculants. Seed inoculation techniques used for research purposes are often not feasible at a commercial scale and there are significant technical challenges in maintaining viable microbial inocula on seed throughout commercial seed treatment processes and storage. Further research is needed before the benefits of a wide range of environmentally sensitive potential seed inoculants can be captured for use in agriculture, ecosystem restoration and bioremediation. There is no single solution to the challenge of improving the ability of seed inoculants to establish and function consistently in the field. Development of novel formulations that maintain the viability of both inoculant and seed during storage will result from multidisciplinary research in microbial and seed physiology and adjuvant chemistry. PMID- 27188776 TI - Enzymes useful for chiral compound synthesis: structural biology, directed evolution, and protein engineering for industrial use. AB - Biocatalysts (enzymes) have many advantages as catalysts for the production of useful compounds as compared to chemical catalysts. The stereoselectivity of the enzymes is one advantage, and thus the stereoselective production of chiral compounds using enzymes is a promising approach. Importantly, industrial application of the enzymes for chiral compound production requires the discovery of a novel useful enzyme or enzyme function; furthermore, improving the enzyme properties through protein engineering and directed evolution approaches is significant. In this review, the significance of several enzymes showing stereoselectivity (quinuclidinone reductase, aminoalcohol dehydrogenase, old yellow enzyme, and threonine aldolase) in chiral compound production is described, and the improvement of these enzymes using protein engineering and directed evolution approaches for further usability is discussed. Currently, enzymes are widely used as catalysts for the production of chiral compounds; however, for further use of enzymes in chiral compound production, improvement of enzymes should be more essential, as well as discovery of novel enzymes and enzyme functions. PMID- 27188777 TI - Microbial diversity and community structure in an antimony-rich tailings dump. AB - To assess the impact of antimony (Sb) on microbial community structure, 12 samples were taken from an Sb tailings pile in Guizhou Province, Southwest China. All 12 samples exhibited elevated Sb concentrations, but the mobile and bioaccessible fractions were small in comparison to total Sb concentrations. Besides the geochemical analyses, microbial communities inhabiting the tailing samples were characterized to investigate the interplay between the microorganisms and environmental factors in mine tailings. In all samples, Proteobacteria and Actinobacteria were the most dominant phyla. At the genus level, Thiobacillus, Limnobacter, Nocardioides, Lysobacter, Phormidium, and Kaistobacter demonstrated relatively high abundances. The two most abundant genera, Thiobacillus and Limnobacter, are characterized as sulfur-oxidizing bacteria and thiosulfate-oxidizing bacteria, respectively, while the genus Lysobacter contains arsenic (As)-resistant bacteria. Canonical correspondence analysis (CCA) indicates that TOC and the sulfate to sulfide ratio strongly shaped the microbial communities, suggesting the influence of the environmental factors in the indigenous microbial communities. PMID- 27188778 TI - Antibacterial metabolites secreted under glucose-limited environment of the mimicked proximal colon model by lactobacilli abundant in infant feces. AB - The most abundance of anti-Salmonella lactic acid bacteria (LAB) was found in feces of naturally born, exclusively breastfed Thai infants. Six strains of Lactobacillus plantarum and one strain of Lactobacillus paracasei were selected and identified. In the co-cultivation assay, L. plantarum subsp. plantarum I62 showed the strongest and broadest antibacterial activity against Escherichia coli, Shigella sonnei, Salmonella Paratyphi A, and Salmonella Typhimurium SA 2093 under the mimicked proximal colon condition, in which glucose and other nutrients were limited. According to GC-MS analysis, the major antibacterial contribution of organic acids secreted by L. plantarum I62 grown in the presence of glucose was dramatically reduced from 95.8 to 41.9 % under glucose-limited niche. The production of low-pK a acids, such as lactic, 1,2-benzenedicarboxylic, and 3 phenyllactic acids, was remarkably dropped. Surprisingly, higher-pK a acids such as 5-chlorobenzimidazole-2-carboxylic, pyroglutamic, palmitic, and oleic acids were enhanced. Moreover, cyclic dipeptides, ketones, alkanes, alcohols, and miscellaneous compounds, which were pH-independent antibacterial metabolites, became dominant. The electron microscopy strongly supported the synergistic attacks of the multiple antibacterial components targeting outer and cytoplasmic membranes leading to severe leakage and cell disruption of Salmonella Typhimurium. This strain poses to be a potential probiotic candidate for effectively controlling and treating human foodborne bacterial infection. PMID- 27188779 TI - Released polysaccharides (RPS) from Cyanothece sp. CCY 0110 as biosorbent for heavy metals bioremediation: interactions between metals and RPS binding sites. AB - Bioremediation of heavy metals using microorganisms can be advantageous compared to conventional physicochemical methods due to the use of renewable resources and efficiencies of removal particularly cations at low concentrations. In this context, cyanobacteria/cyanobacterial extracellular polymeric substances (EPS) emerge as a valid alternative due to the anionic nature and particular composition of these polymers. In this work, various culture fractions of the unicellular cyanobacterium Cyanothece sp. CCY 0110 were employed in bioremoval assays using three of the most common heavy metal pollutants in water bodies copper, cadmium, and lead-separately or in combined systems. Our study showed that the released polysaccharides (RPS) were the most efficient fraction, removing the metal(s) by biosorption. Therefore, this polymer was subsequently used to evaluate the interactions between the metals/RPS binding sites using SEM EDX, ICP-OES, and FTIR. Acid and basic pretreatments applied to the polymer further improve the process efficiency, and the exposure to an alkaline solution seems to alter the RPS conformation. The differences observed in the specific metal bioremoval seem to be mainly due to the RPS organic functional groups available, mainly carboxyl and hydroxyl, than to an ion exchange mechanism. Considering that Cyanothece is a highly efficient RPS-producer and that RPS can be easily separated from the culture, immobilized or confined, this polymer can be advantageous for the establishment/improvement of heavy metal removal systems. PMID- 27188782 TI - Neuro-oncology Virtual Special Issue. PMID- 27188781 TI - Comparison of Phytochemicals and Antioxidant Capacity in Three Bean Varieties Grown in Central Malawi. AB - The aims of the current work were: (1) to study the influence of variety and geographical production area on the total phenolic content, total anthocyanin content, total flavonoid content, total carotenoid content and antioxidant activity in bean varieties (Dimeta, Napirira and Nanyati) from different growing areas in central Malawi, and (2) to evaluate the possibility of establishing a classification based on the geographical areas of the growing regions. A total of 47 bean samples were collected from Makowe, Mphathi, Chuma-Chitsala and Khulungira Zone. These four locations were segregated based on altitude, latitude and longitude. Principal component and hierarchical cluster analysis were used to distinguish and classify among these samples. Significant differences (P < 0.05) in total phenolic content (2.92-4.97 mg/g), total anthocyanin content (14.52 152.31 MUg/g), total flavonoid content (2.01-6.38 mg/g) and oxygen radical absorbance capacity (16.75-24.51 MUmol/g) were found among the different sampled villages, showing a significant effect of the producing region on these parameters. The beans in Makowe had lower polyphenols than in other locations. Results of principal component analysis indicate that phytochemicals and antioxidant capacity could serve as parameters to establish a bean classification according to the geographical area of production. PMID- 27188780 TI - Stimulation of Phenolics, Antioxidant and alpha-Glucosidase Inhibitory Activities During Barley (Hordeum vulgare L.) Seed Germination. AB - The rationale of this study was to enhance the nutritional quality of dry barley seeds. In this study we are evaluating the effect of germination on barley seeds relevant to total phenolic contents, antioxidant activity (in terms of DPPH free radical scavenging) and the in vitro alpha-glucosidase inhibitory activities. Barley seeds were germinated for 18.5, 24, 30, 48, and 67 h and then extracted in water. The total phenolic contents, antioxidant activities and alpha-glucosidase inhibitory activities changed with germination time. More specifically, within the first 48 h of germination the total phenolic content increased from 1.1 mg/g fresh weight (0 h) to 3.4 mg/g fresh weight (48 h) and then slightly reduced by 67 h. Similarly, alpha-glucosidase inhibitory activity was significantly increased from an IC50 128.82 mg/mL (0 h) to an IC50 18.88 mg/mL (48 h) and then slightly reduced by 67 h. Significant maltase inhibitory activity was observed only with 48 h-germinated extract. Antioxidant activities increased continuously from an IC50 15.72 mg/mL at 0 h to and IC50 5.72 mg/mL after 48 h of germination. Based on our observations, barley seed germination was over after 48 h. During the progress of germination phenolic compounds are becoming available and are more easily extracted. After 48 h, lignification is initiated resulting to the decreased total phenolic content and observed antioxidant and carbohydrate hydrolyzing enzyme inhibition activities. The above results indicate the positive effect of germination in barley seeds for enhanced antioxidant and alpha glucosidase inhibitory activities. PMID- 27188783 TI - Individual and collective modes of surface magnetoplasmon in thiolate-protected silver nanoparticles studied by MCD spectroscopy. AB - Large magneto-optical (MO) responses at the energy of localized surface plasmon resonance (LSPR), namely, surface magnetoplasmons, are demonstrated for the first time in thiolate-protected silver nanoparticles with magnetic circular dichroism (MCD) spectroscopy. The samples examined are decanethiol (DT)-, azobenzenethiol (ABT)-, and ABT/DT mixed-monolayer-protected Ag nanoparticles. ABT-protected Ag nanoparticles are somewhat aggregated and thus exhibit a broad, collective mode of plasmonic absorption, whereas other samples with highly-dispersed nanoparticles show an individual mode of LSPR absorption. In all Ag nanoparticles, a derivative-like MCD signal is observed under an applied magnetic field of 1.6 T, which can be explained in terms of two circular modes of magnetoplasmon caused by the increase (or decrease) in the Lorentz force imparted on the free electrons that oscillate in the left (or right) circular orbits in the nanosphere. For the Ag nanoparticles exhibiting an individual LSPR mode, in particular, simultaneous deconvolution analysis of UV-vis absorption and MCD spectra reveal that (i) the amplitude of the magnetoplasmonic component with lower frequency (omega-), resulting from the reduction in the confinement strength of collective electrons by the Lorentz force, is stronger than that with a higher frequency (omega+); (ii) the accurate shift or cyclotron frequency between two magnetoplasmonic modes (omegac = omega+-omega-) is size-dependent, and presents a very large value with implications for the apparent enhancement of the local magnetic-field in the Ag nanoparticles. These results strongly suggest that the Ag-thiolate layer or Ag-S bonding on the nanoparticle surface plays a significant role in the MO enhancement. PMID- 27188784 TI - Successful antibiotic treatment of pulmonary disease caused by Mycobacterium abscessus subsp. abscessus with C-to-T mutation at position 19 in erm(41) gene: case report. AB - BACKGROUND: Mycobacterium abscessus complex (MABC) is the most drug resistant of the mycobacterial pathogens. M. abscessus subsp. abscessus encodes a functional erythromycin ribosomal methylase gene, erm(41), causing inducible macrolide resistance. However, some clinical isolates of M. abscessus subsp. abscessus harboring nonfunctional erm(41) were susceptible to macrolide, even after extended incubation of 14 days. Loss of function of the erm(41) genes was associated with a T-to-C substitution at position 28 of the gene (T28C), leading to an amino acid change from Trp to Arg at codon 10. Pulmonary disease caused by M. abscessus subsp. abscessus strains with an nonfunctional erm(41) (C28 sequevar) may be responsive to macrolide-containing antibiotic regimens. Therefore, all M. abscessus subsp. abscessus strains with a functional erm(41) (T28 sequevar) were thought to be resistant to macrolide with extended incubation. Here, we report the first case of pulmonary disease caused by a strain of M. abscessus subsp. abscessus which was susceptible to macrolide due to T19 sequevar of erm(41) gene. CASE PRESENTATION: A 62-year-old Korean female was referred to our hospital due to chronic cough, sputum, and hemoptysis lasting more than 5 months. The patient's sputum was positive for acid-fast bacilli staining and nontuberculous mycobacteria (NTM) were isolated twice from sputum specimens. The isolate was identified as M. abscessus subsp. abscessus. The isolate had a point mutation of C -> T at position 19 (C19 -> T) in the erm(41) gene, instead of expected C28 sequevar of erm(41), and had no rrl mutation. The isolate displayed a clarithromycin susceptible phenotype with an Arg -> Stop codon change in erm(41). The patient was successfully treated with a macrolide containing regimen. CONCLUSION: This is the first case of pulmonary disease caused by a strain of M. abscessus subsp. abscessus showing clarithromycin susceptible phenotype due to T19 sequevar of the erm(41) gene. The erm(41) gene is clinically important, and non-functional erm alleles may be an important issue for the management of MABC lung disease. The presence of a non-functional erm(41) allele in M. abscessus subsp. abscessus isolates may be associated with better outcomes. PMID- 27188787 TI - An evaluation of the efficacy of solifenacin and darifenacin for prevention of catheter related bladder discomfort: a prospective, randomized, placebo controlled, double blind study. AB - BACKGROUND: Urinary catheterization during surgical interventions causes postoperative catheter related bladder discomfort (CRBD). Antimuscarinic agents are the mainstay of treatment for overactive bladder (OAB). As the symptoms of CRBD mimic to OAB, so we designed this study to assess the efficacy of solifenacin and darifenacin for prevention of CRBD. METHODS: Ninety patients of either sex undergoing elective spine surgery and requiring urinary catheterization were randomly assigned into three groups to receive oral solifenacin 5 mg (Group S), darifenacin 7.5 mg (Group D) and placebo (Group C) 1 hour prior to induction of anesthesia. Anesthesia technique was identical in all the groups. Catheter related bladder discomfort (CRBD) was evaluated in 4-point scale (1 = no discomfort, 2 = mild, 3 = moderate, 4 = severe), on arrival (0 hour) and at 1, 2, and 6 hours postoperatively. Patients were provided patient controlled analgesia with fentanyl for postoperative pain relief. RESULTS: There were no significant differences in demographic profile and fentanyl requirements (P >0.05). The prevalence and severity of CRBD were significantly less in the group D and group S compared with the group C at all time intervals (P <0.05). CONCLUSION: Pretreatment with oral solifenacin or darifenacin reduces catheter related bladder discomfort with no clinically relevant significant side effects. PMID- 27188785 TI - Media multitasking in adolescence. AB - Media use has been on the rise in adolescents overall, and in particular, the amount of media multitasking-multiple media consumed simultaneously, such as having a text message conversation while watching TV-has been increasing. In adults, heavy media multitasking has been linked with poorer performance on a number of laboratory measures of cognition, but no relationship has yet been established between media-multitasking behavior and real-world outcomes. Examining individual differences across a group of adolescents, we found that more frequent media multitasking in daily life was associated with poorer performance on statewide standardized achievement tests of math and English in the classroom, poorer performance on behavioral measures of executive function (working memory capacity) in the laboratory, and traits of greater impulsivity and lesser growth mindset. Greater media multitasking had a relatively circumscribed set of associations, and was not related to behavioral measures of cognitive processing speed, implicit learning, or manual dexterity, or to traits of grit and conscientiousness. Thus, individual differences in adolescent media multitasking were related to specific differences in executive function and in performance on real-world academic achievement measures: More media multitasking was associated with poorer executive function ability, worse academic achievement, and a reduced growth mindset. PMID- 27188786 TI - A reference library of peripheral blood mononuclear cells for SWATH-MS analysis. AB - PURPOSE: Peripheral blood mononuclear cells (PBMCs) play quite diverse and important roles in monitoring immune homeostasis. Thus, this subset of blood cells may provide access to potential physiological relevant biomolecules, namely proteins. For this reason, PBMCs represent a promising alternative biological sample in scientific research, particularly as a source of potential biomarkers. Prior proteomic studies of PBMCs from healthy individuals focused only on a qualitative analysis, lacking the quantitative analysis information crucial for biomarker discovery, since most of the biological alterations result in slight changes in protein levels, not affecting the overall proteome composition. Therefore, this study aimed to provide a comprehensive PBMCs proteome library to be use in protein quantification by SWATH-MS. EXPERIMENTAL DESIGN: A SWATH-MS library was generated by a comprehensive 2D-LC-MS/MC analysis of a pooled sample of PBMCs from 6 different donors. GeLC-SWATH-MS analysis of the 6 donors was further used to test the generated library. RESULTS: The generated library comprises 1102 proteins involved in diverse human diseases and in immune system related pathways. When tested in biological samples this library allowed the quantification of 920 different proteins, and around 700 per individual. CONCLUSIONS AND CLINICAL RELEVANCE: The provided PBMCs proteome library will be useful in further studies that aim to reproducibly quantify a large number of PBMCs' proteins without the need to perform protein identification. Furthermore, this robust microLC-SWATH-MS analysis is suitable with clinical practice. PMID- 27188788 TI - Point-of-care-based protocol with first-line therapy with coagulation factor concentrates is associated with decrease allogenic blood transfusion and costs in cardiovascular surgery: an Italian single-center experience. AB - BACKGROUND: Transfusion in patients having cardiac surgery has been associated with increased morbidity, mortality, and costs. This analysis assessed the impact of a rotational thromboelastometry (ROTEM(r))- and functional platelet assessment (Multiplate(r))-based protocol for bleeding management on perioperative outcomes and costs in patients undergoing cardiac surgery. METHODS: This retrospective analysis of the records of all patients who underwent cardiac surgery at the Hesperia Hospital, Modena, Italy, from December 2012 to December 2013 compared outcomes and costs of bleeding management for the two 6-month periods before/after introduction of the ROTEM- and Multiplate-based protocol. Descriptive and correlation analysis were performed as appropriate. Propensity score matching and its correlation analysis were performed. RESULTS: Data from 768 consecutive patients (mean age ~69 years, ~66% male) were included; 50.7% and 49.3% of patients had surgery before and after protocol introduction, respectively. Significantly fewer patients required transfusions of packed red blood cells after the protocol introduction over the 24 hours postsurgery (100 vs. 197 patients; P<0.001) and during ICU stay (134 vs. 221 patients; P<0.001). A significantly greater proportion of patients treated after protocol introduction received prothrombin complex concentrate (31 vs. 16; P<0.05) and fibrinogen concentrate (36 vs. 13; P<0.001). A significantly greater proportion of patients treated after protocol introduction had an ICU stay duration <48 hours (81.5% vs. 71.5%; P<0.001). ROTEM-based bleeding management was associated with a saving of ?128,676.23 for the 379 patients undergoing surgery post-protocol introduction (?339.52 per patient). CONCLUSIONS: ROTEM-guided bleeding management in patients undergoing cardiac surgery was cost-effective and associated with an increase of administration of coagulation factor concentrates and a decrease of ICU length of stay. PMID- 27188789 TI - A multiband perfect absorber based on hyperbolic metamaterials. AB - In recent years, considerable research efforts have been focused on near-perfect and perfect light absorption using metamaterials spanning frequency ranges from microwaves to visible frequencies. This relatively young field is currently facing many challenges that hampers its possible practical applications. In this paper, we present grating coupled-hyperbolic metamaterials (GC-HMM) as multiband perfect absorber that can offer extremely high flexibility in engineering the properties of electromagnetic absorption. The fabricated GC-HMMs exhibit several highly desirable features for technological applications such as polarization independence, wide angle range, broad- and narrow- band modes, multiband perfect and near perfect absorption in the visible to near-IR and mid-IR spectral range. In addition, we report a direct application of the presented system as an absorption based plasmonic sensor with a record figure of merit for this class of sensors. PMID- 27188790 TI - Glioma. AB - Gliomas are primary brain tumours that are thought to derive from neuroglial stem or progenitor cells. On the basis of their histological appearance, they have been traditionally classified as astrocytic, oligodendroglial or ependymal tumours and assigned WHO grades I-IV, which indicate different degrees of malignancy. Tremendous progress in genomic, transcriptomic and epigenetic profiling has resulted in new concepts of classifying and treating gliomas. Diffusely infiltrating gliomas in adults are now separated into three overarching tumour groups with distinct natural histories, responses to treatment and outcomes: isocitrate dehydrogenase (IDH)-mutant, 1p/19q co-deleted tumours with mostly oligodendroglial morphology that are associated with the best prognosis; IDH-mutant, 1p/19q non-co-deleted tumours with mostly astrocytic histology that are associated with intermediate outcome; and IDH wild-type, mostly higher WHO grade (III or IV) tumours that are associated with poor prognosis. Gliomas in children are molecularly distinct from those in adults, the majority being WHO grade I pilocytic astrocytomas characterized by circumscribed growth, favourable prognosis and frequent BRAF gene fusions or mutations. Ependymal tumours can be molecularly subdivided into distinct epigenetic subgroups according to location and prognosis. Although surgery, radiotherapy and alkylating agent chemotherapy are still the mainstay of treatment, individually tailored strategies based on tumour-intrinsic dominant signalling pathways and antigenic tumour profiles may ultimately improve outcome. For an illustrated summary of this Primer, visit: http://go.nature.com/TXY7Ri. PMID- 27188791 TI - RalA employs GRK2 and beta-arrestins for the filamin A-mediated regulation of trafficking and signaling of dopamine D2 and D3 receptor. AB - Filamin A (FLNA) is known to act as platform for the signaling and intracellular trafficking of various GPCRs including dopamine D2 and D3 receptors (D2R, D3R). To understand molecular mechanisms involved in the FLNA-mediated regulation of D2R and D3R, comparative studies were conducted on the signaling and intracellular trafficking of the D2R and D3R in FLNA-knockdown cells, with a specific focus on the roles of the proteins that interact with FLNA and the D2R and D3R. Lowering the level of cellular FLNA caused an elevation in RalA activity and resulted in selective interference with the normal intracellular trafficking and signaling of the D2R and D3R, through GRK2 and beta-arrestins, respectively. Knockdown of FLNA or coexpression of active RalA interfered with the recycling of the internalized D2R and resulted in the development of receptor tolerance. Active RalA was found to interact with GRK2 to sequester it from D2R. Knockdown of FLNA or coexpression of active RalA prevented D3R from coupling with G protein. The selective involvement of GRK2- and beta-arrestins in the RalA mediated cellular processes of the D2R and D3R was achieved via their different modes of interactions with the receptor and their distinct functional roles in receptor regulation. Our results show that FLNA is a multi-functional protein that acts as a platform on which D2R and D3R can interact with various proteins, through which selective regulation of these receptors occurs in combination with GRK2 and beta-arrestins. PMID- 27188792 TI - beta-III tubulin modulates the behavior of Snail overexpressed during the epithelial-to-mesenchymal transition in colon cancer cells. AB - Class III beta-tubulin (TUBB3) is a marker of drug resistance expressed in a variety of solid tumors. Originally, it was described as an important element of chemoresistance to taxanes. Recent studies have revealed that TUBB3 is also involved in an adaptive response to a microenvironmental stressor, e.g. low oxygen levels and poor nutrient supply in some solid tumors, independently of the microtubule targeting agent. Furthermore, it has been demonstrated that TUBB3 is a marker of biological aggressiveness associated with modulation of metastatic abilities in colon cancer. The epithelial-to-mesenchymal transition (EMT) is a basic cellular process by which epithelial cells lose their epithelial behavior and become invasive cells involved in cancer metastasis. Snail is a zinc-finger transcription factor which is able to induce EMT through the repression of E cadherin expression. In the presented studies we focused on the analysis of the TUBB3 role in EMT-induced colon adenocarcinoma cell lines HT-29 and LS180. We observed a positive correlation between Snail presence and TUBB3 upregulation in tested adenocarcinoma cell lines. The cellular and behavioral analysis revealed for the first time that elevated TUBB3 level is functionally linked to increased cell migration and invasive capability of EMT induced cells. Additionally, the post-transcriptional modifications (phosphorylation, glycosylation) appear to regulate the cellular localization of TUBB3 and its phosphorylation, observed in cytoskeleton, is probably involved in cell motility modulation. PMID- 27188793 TI - Adenosine signalling mediates the anti-inflammatory effects of the COX-2 inhibitor nimesulide. AB - Extracellular adenosine formation from ATP is controlled by ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase/CD39) and ecto-5'-nucleotidase (e 5NT/CD73); the latter converts AMP to adenosine and inorganic phosphate, representing the rate limiting step controlling the ratio between extracellular ATP and adenosine. Evidence that cellular expression and activity of CD39 and CD73 may be subject to changes under pathophysiological conditions has identified this pathway as an endogenous modulator in several diseases and was shown to be involved in the molecular mechanism of drugs, such as methotrexate, salicylates , interferon-beta. We evaluated whether CD73/adenosine/A2A signalling pathway is involved in nimesulide anti-inflammatory effect, in vivo and in vitro. We found that the adenosine A2A agonist, 4-[2-[[6-amino-9-(N-ethyl-beta-d ribofuranuronamidosyl)-9H-purin-2-yl]amino]ethyl]benzenepropanoic acid hydrochloride (CGS21680, 2mg/kg ip.), inhibited carrageenan-induced rat paw oedema and the effect was reversed by co-administration of the A2A antagonist -(2 [7-amino-2-[2-furyl][1,2,4]triazolo[2,3-a][1,3,5]triazin-5-yl-amino]ethyl)phenol (ZM241385; 3mg/kg i.p.). Nimesulide (5mg/kg i.p.) anti-inflammatory effect was inhibited by pre-treatment with ZM241385 (3mg/kg i.p.) and by local administration of the CD73 inhibitor, adenosine 5'-(alpha,beta methylene)diphosphate (APCP; 400MUg/paw). Furthermore, we found increased activity of 5'-nucleotidase/CD73 in paws and plasma of nimesulide treated rats, 4h following oedema induction. In vitro, the inhibitory effect of nimesulide on nitrite and prostaglandin E2 production by lipopolysaccharide-activated J774 cell line was reversed by ZM241385 and APCP. Furthermore, nimesulide increased CD73 activity in J774 macrophages while it did not inhibit nitrite accumulation by lipopolysaccharide-activated SiRNA CD73 silenced J774 macrophages. Our data demonstrate that the anti-inflammatory effect of nimesulide in part is mediated by CD73-derived adenosine acting on A2A receptors. PMID- 27188794 TI - An Evaluation of Indian Consumers' Reporting of Suspected Adverse Drug Reactions with a Designated Reporting Form. AB - BACKGROUND: The Pharmacovigilance Program of India recently initiated a process for direct patient reporting of Adverse Drug Reactions (ADRs) with a designated form. PATIENTS AND METHODS: A survey of 200 patients reporting ADRs filling the form. Forms were analysed for patient data, the suspected medication(s), ADRs and possible causality. RESULTS: 54.3% of respondents provided their contact information; the implicated medicine was mentioned in 60% and the description of ADRs in 80% although 46.2% were not interpretable. The severity of ADRs was mentioned in 73.5%. No responder filled the expiry date component of the implicated modification and a causality assessment from most forms was unclassifiable (57%) or unclassified (26%). Details of concomitant drugs were missing. CONCLUSION: Missing information was a deterrent in analysing the consumer ADR reports for signal detection. It is recommended that the following fields are highlighted in the form: consumer's initials, address, date suspected reaction started, description of event, name, dose, and the reason for the use the medication as well as its expiry date. These should be mandatory in the existing form and new fields added for weight and height, batch number for vaccines and biological products, de challenge and rechallenge results to the suspected medicine and concomitantly used medicines. To improve the quality of information in the consumer reporting form an awareness campaign is also suggested. PMID- 27188796 TI - Aqueous ozone solutions for pesticide removal from potatoes. AB - The presence of pesticide residues in potatoes is of concern because of the potential impact to human health due to the high consumption of this vegetable. In this study, aqueous solutions with and without ozone saturation as postharvest wash treatment at pH 4.0, 7.0, and 9.0 were tested to remove chlorothalonil from potatoes. The method used for pesticide analysis has been validated, presenting recovery values of 94-103%, with variations in the repeatability coefficients of <=10.6%, and a quantification limit of 0.05 mg kg-1 Regardless of pH, treatment with aqueous ozone solutions removed 70-76% of the pesticide present in the potato. In the no-ozone treatments, the percentage average removal of chlorothalonil residues in potatoes was only 36%. Over 24 days of storage, the quality of potatoes washed with aqueous ozone solutions was not significantly different from those washed with pure water. PMID- 27188795 TI - Efficacy of transcranial direct current stimulation (tDCS) in reducing consumption in patients with alcohol use disorders: study protocol for a randomized controlled trial. AB - BACKGROUND: Approximately 15 million persons in the European Union and 10 million persons in the USA are alcohol-dependent. The global burden of disease and injury attributable to alcohol is considerable: worldwide, approximately one in 25 deaths in 2004 was caused by alcohol. At the same time, alcohol use disorders remain seriously undertreated. In this context, alternative or adjunctive therapies such as brain stimulation may play a prominent role. The early results of studies using transcranial direct current stimulation found that stimulations delivered to the dorsolateral prefrontal cortex result in a significant reduction of craving and an improvement of the decision-making processes in various additive disorders. We, therefore, hypothesize that transcranial direct current stimulation can lead to a decrease in alcohol consumption in patients suffering from alcohol use disorders. METHODS/DESIGN: We report the protocol of a randomized, double-blind, placebo-controlled, parallel-group trial, to evaluate the efficacy of transcranial direct current stimulation on alcohol reduction in patients with an alcohol use disorder. The study will be conducted in 14 centers in France and Monaco. Altogether, 340 subjects over 18 years of age and diagnosed with an alcohol use disorder will be randomized to receive five consecutive twice daily sessions of either active or placebo transcranial direct current stimulation. One session consists in delivering a current flow continuously (anode F4; cathode F3) twice for 13 minutes, with treatments separated by a rest interval of 20 min. Efficacy will be evaluated using the change from baseline (alcohol consumption during the 4 weeks before randomization) to 24 weeks in the total alcohol consumption and number of heavy drinking days. Secondary outcome measures will include alcohol craving, clinical and biological improvements, and the effects on mood and quality of life, as well as cognitive and safety assessments, and, for smokers, an assessment of the effects of transcranial direct current stimulation on tobacco consumption. DISCUSSION: Several studies have reported a beneficial effect of transcranial direct current stimulation on substance use disorders by reducing craving, impulsivity, and risk-taking behavior, and suggest that transcranial direct current stimulation may be a promising treatment in addiction. However, to date, no studies have included sufficiently large samples and sufficient follow-up to confirm the hypothesis. Results from this large randomized controlled trial will give a better overview of the therapeutic potential of transcranial direct current stimulation in alcohol use disorders. TRIAL REGISTRATION: Clinical Trials Gov, NCT02505126 (registration date: July 15 2015). PMID- 27188797 TI - Donor risk indices in pancreas allocation in the Eurotransplant region. AB - Pancreas donor selection and recognition are important to cope with increasing organ shortage. We aim to show that the PDRI is more useful than the P-PASS to predict acceptance and should thus be preferred over P-PASS. Eurotransplant donors from 2004 until 2014 were included in this study. PDRI logistical factors were set to reference to purely reflect donor quality (PDRI donor ). PDRI and P PASS association with allocation outcome was studied using area under the receiver operating characteristic curve (AUROC). Regional differences in donor quality were also investigated. Of the 10 444 pancreata that were reported, 6090 (58.3%) were accepted and 2947 (28.2%) were transplanted. We found that P-PASS was inferior to PDRIdonor in its ability to predict organ reporting, acceptance, and transplantation: AUC 0.63, 0.67 and 0.73 for P-PASS vs. 0.78, 0.79 and 0.84 for PDRIdonor , respectively. Furthermore, there were significant differences in donor quality among different Eurotransplant countries, both in reported donors and in transplanted organs. PDRI is a powerful predictor of allocation outcome and should be preferred over P-PASS. Proper donor selection and recognition, and possibly a more liberal approach toward inferior quality donors, may increase donation and transplant rates. PMID- 27188798 TI - Correction. PMID- 27188800 TI - Correction. PMID- 27188799 TI - Analogue simulation of pharyngeal airflow response to Twin Block treatment in growing patients with Class II(1) and mandibular retrognathia. AB - The flow dynamics of respiratory airflow is the basic factor that influences the ventilation function of the upper airway. This research aimed to investigate the pharyngeal flow field characteristics after Twin Block (TB) treatment in growing patients with Class II(1) and mandibular retrognathia by computation fluid dynamics (CFD) simulation. Cone beam computed tomography (CBCT) scans of patients who have completed TB treatment (n = 30) and about to accept TB treatment (n = 30) were reconstructed. After CFD simulation, correlations between the pharyngeal pressure drop and morphological parameters were further analyzed. During inspiration, we found that the pressure minimum occurred in the hypopharynx, while the maximum pressure drop and velocity was located in the oropharynx. After TB treatment, the oropharynx and hypopharynx showed significant differences in airflow features, and the most obvious change was observed in the oropharynx. A significant correlation was discovered between the change amount of oropharyngeal pressure drop and volume (r = 0.694, p = 0.001), mean cross-sectional area (r = 0.859, p = 0.000), and ratio of the minimum and mean cross-sectional area (r = 0.898, p = 0.000) of the oropharynx. Our research suggested that the pharyngeal airflow characteristics response positively to mandibular advancement with the enlargement in volume, cross-sectional area and more uniform oropharyngeal area distribution. PMID- 27188801 TI - Tunnelled haemodialysis catheter and haemodialysis outcomes: a retrospective cohort study in Zagreb, Croatia. AB - OBJECTIVES: Studies have reported that the tunnelled dialysis catheter (TDC) is associated with inferior haemodialysis (HD) patient survival, in comparison with arteriovenous fistula (AVF). Since many cofactors may also affect survival of HD patients, it is unclear whether the greater risk for survival arises from TDC per se, or from associated conditions. Therefore, the aim of this study was to determine, in a multivariate analysis, the long-term outcome of HD patients, with respect to vascular access (VA). DESIGN: Retrospective cohort study. PARTICIPANTS: This retrospective cohort study included all 156 patients with a TDC admitted at University Hospital Merkur, from 2010 to 2012. The control group consisted of 97 patients dialysed via AVF. The groups were matched according to dialysis unit and time of VA placement. The site of choice for the placement of the TDC was the right jugular vein. Kaplan-Meier analysis with log-rank test was used to assess patient survival. Multivariate Cox regression analysis was used to determine independent variables associated with patient survival. PRIMARY OUTCOME MEASURES: Patient survival with respect to VA. RESULTS: The cumulative 1-year survival of patients who were dialysed exclusively via TDC was 86.4% and of those who were dialysed exclusively via AVF, survival was 97.1% (p=0.002). In multivariate Cox regression analysis, male sex and older age were independently negatively associated with the survival of HD patients, while shorter HD vintage before the creation of the observed VA, hypertensive renal disease and glomerulonephritis were positively associated with survival. TDC was an independent risk factor for survival of HD patients (HR 23.0, 95% CI 6.2 to 85.3). CONCLUSION: TDC may be an independent negative risk factor for HD patient survival. PMID- 27188802 TI - A cross-sectional study of hyponatraemia among elderly patients with heart failure in Uganda. AB - BACKGROUND: Hyponatraemia is a common electrolyte disturbance among older patients. We determined the prevalence of and factors associated with hyponatraemia among older patients with predominantly acute decompensated heart failure attending a tertiary hospital in Kampala, Uganda. OBJECTIVES: Main study aim: (1) to determine the prevalence of hyponatraemia among patients aged 60 years and above with heart failure attending Mulago National Referral Hospital; (2) to describe the factors associated with hyponatraemia among patients aged 60 years and above with heart failure attending Mulago National Referral Hospital. SETTING: The study was conducted in one tertiary hospital located in the northeast of Kampala, Uganda. PARTICIPANTS: 400 adults aged 60 years and above were identified for the study. Of these, 188 were excluded as they did not fulfil the inclusion criteria and one declined to participate, leaving a final study group of 211 older adults aged 60 years and above, with a clinical diagnosis of heart failure using Framingham's criteria. RESULTS: The prevalence of hyponatraemia was 24.2% (51/211). Hyponatraemia was mainly found in patients with mild-to-moderate heart failure, New York Heart Association classes 2 and 3. Of the 51 patients with hyponatraemia, 27 (52.9%) had mild hyponatraemia, while 24 (47.1%) had moderate to severe hyponatraemia of 130-125 mmol/L. History of vomiting (OR=2.94, 95% CI 1.29 to 6.70, p=0.010) and use of loop diuretics (OR=2.71, 95% CI 1.13 to 6.52, p=0.026) were identified as independent factors associated with hyponatraemia among older patients with heart failure. CONCLUSIONS: Our study revealed a relatively high prevalence of hyponatraemia among older patients with mild to moderate heart failure. Patients presenting with a history of vomiting from any cause or use of loop diuretics were more likely to have hyponatraemia. PMID- 27188803 TI - Telerehabilitation after total knee replacement in Italy: cost-effectiveness and cost-utility analysis of a mixed telerehabilitation-standard rehabilitation programme compared with usual care. AB - OBJECTIVES: To assess cost-effectiveness and cost utility of telerehabilitation (TR) versus standard rehabilitation (SR) after total knee replacement (TKR). DESIGN: Markov decision modelling of cost-effectiveness and cost-utility analysis based on patient-level and secondary data sources employing Italian National Health Service (NHS; Ita-NHS) and Society perspectives. SETTING: Primary care units (PCUs) in Italy. PARTICIPANTS: Patients discharged after TKR. INTERVENTIONS: Mixed SR-TR service (10 face-to-face sessions and 10 telesessions) versus SR (20 face-to-face sessions) PRIMARY AND SECONDARY OUTCOME MEASURES: The incremental cost per additional knee flexion range of motion (ROM) and per QALY gained by SR-TR compared with SR. Second, we considered the probability of being cost-effective and the probability of being more effective and less expensive. RESULTS: TR appears to be the cost-effective in the base case and in all of the considered scenarios, but is no longer more effective and less expensive if transportation costs are excluded. Comparing SR-TR with SR, the incremental cost effectiveness ratio (ICER) adopting the Ita-NHS perspective for the base case was -?117/ROM gained. The cost-effectiveness probability for SR-TR was 0.98 (ceiling ratio: ?50/ROM), while the joint probability of being more effective and less expensive was 0.87. Assuming that TR would increase health-related quality of life (HRQOL) utilities by 2.5%, the ICER adopting Ita-NHS perspective is ?960/QALY (cost-effectiveness probability: 1; ceiling ratio: ?30 000/QALY). All the performed sensitivity analyses did not change the conclusions, but if transportation costs were excluded, the probability for SR-TR of being more clinically effective and less expensive reduced to 0.56. CONCLUSIONS: The analysis suggested SR-TR to be cost-effective, even less expensive and more effective if the PCUs provide ambulance transportations. However, the uncertainty related to TR costs, HRQOL and long-term clinical outcomes raises important topics for future research, which should be addressed to confirm our estimates. TRIAL REGISTRATION NUMBER: ISRCTN45837371. PMID- 27188804 TI - Study on the safety and efficacy of miltefosine for the treatment of children and adolescents with post-kala-azar dermal leishmaniasis in Bangladesh, and an association of serum vitamin E and exposure to arsenic with post-kala-azar dermal leishmaniasis: an open clinical trial and case-control study protocol. AB - INTRODUCTION: Post-kala-azar dermal leishmaniasis (PKDL) is a dermatological complication that occurs primarily among treated visceral leishmaniasis (VL) patients, and sporadically in a few without a history of VL. It mostly affects children and adolescents but is also common in adults. The conventional treatment with 120 intramuscular injections of sodium stibogluconate (SSG) is phasing out. Miltefosine (MF) is the only eventual alternative to SSG; however, its efficacy and safety profiles for treatment of children and adolescents with PKDL are lacking. In addition, risk factors for PKDL are poorly investigated. Host genetic, nutritional and environmental factors could be potential risk factors. As such, here we propose to evaluate the efficacy and safety of MF for 12 weeks at an allometric dose for children and adolescents with PKDL, and also to explore potential risk factors for PKDL. METHODS AND ANALYSIS: A cross-sectional survey will look for suspected participants with PKDL among treated VL children and adolescents, a subsequent open clinical trial with MF at allometric dose, with a follow-up at 12 months. A case-control study will be carried out for PKDL risk factors. Assuming 95% cure rate, 95% CI and alpha=0.05, a sample size of 73 children with PKDL is needed. Considering an attrition rate of 10%, the final sample size is 80 children in each group. Descriptive and analytical analyses will be performed. Primary outcome is safety and cure rate of 12 weeks of treatment with MF. ETHICS AND DISSEMINATION: International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B) Ethical Review Committee (ERC) approved the protocol (PR#013045). Written informed consent will be taken from all participants and their guardians (in case of minor). A Data and Safety Monitoring Board (DSMB) of ICDDR,B ERC will monitor all study activities to ensure the safety of the participants. TRIAL REGISTRATION NUMBER: NCT02193022; Pre-results. PMID- 27188805 TI - Nationwide population-based cohort study of uterine rupture in Belgium: results from the Belgian Obstetric Surveillance System. AB - OBJECTIVES: We aimed to assess the prevalence of uterine rupture in Belgium and to evaluate risk factors, management and outcomes for mother and child. DESIGN: Nationwide population-based prospective cohort study. SETTING: Emergency obstetric care. Participation of 97% of maternity units covering 98.6% of the deliveries in Belgium. PARTICIPANTS: All women with uterine rupture in Belgium between January 2012 and December 2013. 8 women were excluded because data collection forms were not returned. RESULTS: Data on 90 cases of confirmed uterine rupture were obtained, of which 73 had a previous Caesarean section (CS), representing an estimated prevalence of 3.6 (95% CI 2.9 to 4.4) per 10 000 deliveries overall and of 27 (95% CI 21 to 33) and 0.7 (95% CI 0.4 to 1.2) per 10 000 deliveries in women with and without previous CS, respectively. Rupture occurred during trial of labour after caesarean section (TOLAC) in 57 women (81.4%, 95% CI 68% to 88%), with a high rate of augmented (38.5%) and induced (29.8%) labour. All patients who underwent induction of labour had an unfavourable cervix at start of induction (Bishop Score <=7 in 100%). Other uterine surgery was reported in the history of 22 cases (24%, 95% CI 17% to 34%), including 1 case of myomectomy, 3 cases of salpingectomy and 2 cases of hysteroscopic resection of a uterine septum. 14 cases ruptured in the absence of labour (15.6%, 95% CI 9.5% to 24.7%). No mothers died; 8 required hysterectomy (8.9%, 95% CI 4.6% to 16.6%). There were 10 perinatal deaths (perinatal mortality rate 117/1000 births, 95% CI 60 to 203) and perinatal asphyxia was observed in 29 infants (34.5%, 95% CI 25.2% to 45.1%). CONCLUSIONS: The prevalence of uterine rupture in Belgium is similar to that in other Western countries. There is scope for improvement through the implementation of nationally adopted guidelines on TOLAC, to prevent use of unsafe procedures, and thereby reduce avoidable morbidity and mortality. PMID- 27188807 TI - Influence of advancing age on clinical presentation, treatment efficacy and safety, and long-term outcome of pre-excitation syndromes: a retrospective cohort study of 961 patients included over a 25-year period. AB - OBJECTIVES: There are very little data on pre-excitation syndrome (PS) in the elderly. We investigated the influence of advancing age on clinical presentation, treatment and long-term outcome of PS. SETTING: Single-centre retrospective study of patient files. PARTICIPANTS: In all, 961 patients (72 patients >=60 years (mean 68.5+/-6), 889 patients <60 years (mean 30.5+/-14)) referred for overt pre excitation and indication for electrophysiological study (EPS) were followed for 5.3+/-5 years. Usual care included 24 h Holter monitoring, echocardiography and EPS. Patients underwent accessory pathway (AP) ablation if necessary. PRIMARY AND SECONDARY OUTCOME MEASURES: Occurrence of atrial fibrillation (AF) or procedure induced adverse event. RESULTS: Electrophysiological data and recourse to AP ablation (43% vs 48.5%, p=0.375) did not significantly differ between the groups. Older patients more often had symptomatic forms (81% vs 63%, p=0.003), history of spontaneous AF (8% vs 3%, p=0.01) or adverse presentation (poorly tolerated arrhythmias: 18% vs 7%, p=0.0009). In multivariable analysis, patients >=60 years had a significantly higher risk of history of AF (OR=4.2, 2.1 to 8.3, p=0.001) and poorly tolerated arrhythmias (OR=3.8, 1.8 to 8.1, p=0.001). Age >=60 years was associated with an increased major AP ablation complication risk (10% vs 1.9%, p=0.006). During follow-up, occurrence of AF (13.9% vs 3.6%, p<0.001) and incidence of poorly tolerated tachycardia (4.2% vs 0.6%, p=0.001) were more frequent in patients >=60 years, although frequency of ablation failure or recurrence was similar (20% vs 15.5%, p=0.52). In multivariable analysis, patients >=60 years had a significantly higher risk of AF (OR=2.9, 1.2 to 6.8, p<=0.01). CONCLUSIONS: In this retrospective monocentre study, patients >=60 years referred for PS work up appeared at higher risk of AF and adverse presentation, both prior and after the work up. These results suggest that, in elderly patients, the decision for EPS and AP ablation should be discussed in light of their suspected higher risk of events and ablation complications. However, these findings should be further validated in future prospective multicentre studies. PMID- 27188806 TI - Geographical variation in glaucoma prescribing trends in England 2008-2012: an observational ecological study. AB - OBJECTIVES: To explore (1) the national trend in population-adjusted prescription rates for glaucoma and ocular hypertension (OHT) in England and (2) any geographical variation in glaucoma/OHT prescribing trends and its association with established risk factors for primary open-angle glaucoma (POAG) at the population level. DESIGN: Observational ecological study. SETTING: Primary care in England 2008-2012. PARTICIPANTS: All patients who received 1 or more of the 37 778 660 glaucoma/OHT prescription items between 2008 and 2012. PRIMARY AND SECONDARY OUTCOME MEASURE METHODS: Glaucoma/OHT prescription statistics for England and its constituent primary care trusts (PCTs) between 2008 and 2012 were divided by annual population estimates to give prescription rates per 100 000 population aged >=40 years. To examine regional differences, prescription rates and the change in prescription rates between 2008 and 2012 for PCTs were separately entered into multivariable linear regression models with the population proportion aged >=60 years; the proportion of males; the proportion of West African Diaspora (WAD) ethnicity; PCT funding per capita; Index of Multiple Deprivation 2010 score and its domains. RESULTS: Between 2008 and 2012, glaucoma/OHT prescriptions increased from 28 029 to 31 309 items per 100 000 population aged >=40 years. Between PCTs, nearly a quarter of the variation in prescription rates in 2008 and 2012 could be attributed to age, WAD ethnicity and male gender. The change in prescription rates between 2008 and 2012 was only modestly correlated with age (p=0.003, beta=0.234), and income deprivation (p=0.035, beta=-0.168). CONCLUSIONS: Increased population-adjusted glaucoma/OHT prescription rates in the study period were likely due to increased detection of POAG and OHT cases at risk of POAG. Between PCTs, regional variation in overall prescription rates was partly attributable to demographic risk factors for POAG, although the change in prescription rates was only modestly correlated with the same risk factors, suggesting potential variation in practice. PMID- 27188808 TI - Perceptions of coping with non-disease-related life stress for women with osteoarthritis: a qualitative analysis. AB - OBJECTIVE: Coping with arthritis-related stress has been extensively studied. However, limited evidence exists regarding coping with stress extraneous to the disease (life stress). This study explored life stress and coping in a subset of older women with osteoarthritis from a larger longitudinal study. SETTING: An Australian regional university. DESIGN: This qualitative study involved semistructured telephone interviews. Potential participants were mailed a letter of invitation/participant information statement by the Australian Longitudinal Study on Women's Health (ALSWH). Invitations were sent out in small batches (primarily 10). Interviews were conducted until data saturation was achieved using a systematic process (n=19). Digitally recorded interviews were transcribed verbatim and deidentified. Data were thematically analysed. PARTICIPANTS: Women who indicated being diagnosed or treated for arthritis in the previous 3 years in the fifth survey of the ALSWH (conducted in 2007) provided the sampling frame. Potential participants were randomly sampled by a blinded data manager using a random number generator. RESULTS: Coping with life stress involved both attitudinal coping processes developed early in life (ie, stoicism) and transient cognitive and support-based responses. Women also described a dualistic process involving a reduction in the ability to cope with ongoing stress over time, coupled with personal growth. CONCLUSIONS: This is the first study to examine how individuals cope with non-arthritis-related stress. The findings add to the current understanding of stress and coping, and have implications regarding the prevention of arthritis in women. Importantly, this study highlighted the potential detrimental impact of persistent coping patterns developed early in life. Public health campaigns aimed at stress mitigation and facilitation of adaptive coping mechanisms in childhood and adolescence may assist with arthritis prevention. PMID- 27188810 TI - Determinants of adherence to seasonal influenza vaccination among healthcare workers from an Italian region: results from a cross-sectional study. AB - OBJECTIVES: Notwithstanding decades of efforts to increase the uptake of seasonal influenza (flu) vaccination among European healthcare workers (HCWs), the immunisation rates are still unsatisfactory. In order to understand the reasons for the low adherence to flu vaccination, a study was carried out among HCWs of two healthcare organisations in Liguria, a region in northwest Italy. METHODS: A cross-sectional study based on anonymous self-administered web questionnaires was carried out between October 2013 and February 2014. Through univariate and multivariate regression analysis, the study investigated the association between demographic and professional characteristics, knowledge, beliefs and attitudes of the study participants and (i) the seasonal flu vaccination uptake in the 2013/2014 season and (ii) the self-reported number of flu vaccination uptakes in the six consecutive seasons from 2008/2009 to 2013/2014. RESULTS: A total of 830 HCWs completed the survey. Factors statistically associated with flu vaccination uptake in the 2013/2014 season were: being a medical doctor and agreeing with the statements 'flu vaccine is safe', 'HCWs have a higher risk of getting flu' and 'HCWs should receive flu vaccination every year'. A barrier to vaccination was the belief that pharmaceutical companies influence decisions about vaccination strategies. DISCUSSION: All the above-mentioned factors, except the last one, were (significantly) associated with the number of flu vaccination uptakes self reported by the respondents between season 2008/2009 and season 2013/2014. Other significantly associated factors appeared to be level of education, being affected by at least one chronic disease, and agreeing with mandatory flu vaccination in healthcare settings. CONCLUSIONS: This survey allows us to better understand the determinants of adherence to vaccination as a fundamental preventive strategy against flu among Italian HCWs. These findings should be used to improve and customise any future promotion campaigns to overcome identified barriers to immunisation. PMID- 27188809 TI - Access to primary care for socioeconomically disadvantaged older people in rural areas: a realist review. AB - OBJECTIVE: The aim of this review is to identify and understand the contexts that effect access to high-quality primary care for socioeconomically disadvantaged older people in rural areas. DESIGN: A realist review. DATA SOURCES: MEDLINE and EMBASE electronic databases and grey literature (from inception to December 2014). ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Broad inclusion criteria were used to allow articles which were not specific, but might be relevant to the population of interest to be considered. Studies meeting the inclusion criteria were assessed for rigour and relevance and coded for concepts relating to context, mechanism or outcome. ANALYSIS: An overarching patient pathway was generated and used as the basis to explore contexts, causal mechanisms and outcomes. RESULTS: 162 articles were included. Most were from the USA or the UK, cross-sectional in design and presented subgroup data by age, rurality or deprivation. From these studies, a patient pathway was generated which included 7 steps (problem identified, decision to seek help, actively seek help, obtain appointment, get to appointment, primary care interaction and outcome). Important contexts were stoicism, education status, expectations of ageing, financial resources, understanding the healthcare system, access to suitable transport, capacity within practice, the booking system and experience of healthcare. Prominent causal mechanisms were health literacy, perceived convenience, patient empowerment and responsiveness of the practice. CONCLUSIONS: Socioeconomically disadvantaged older people in rural areas face personal, community and healthcare barriers that limit their access to primary care. Initiatives should be targeted at local contextual factors to help individuals recognise problems, feel welcome, navigate the healthcare system, book appointments easily, access appropriate transport and have sufficient time with professional staff to improve their experience of healthcare; all of which will require dedicated primary care resources. PMID- 27188811 TI - Symptoms of depression and all-cause mortality in farmers, a cohort study: the HUNT study, Norway. AB - OBJECTIVES: To explore all-cause mortality and the association between symptoms of depression and all-cause mortality in farmers compared with other occupational groups, using a prospective cohort design. METHODS: We included adult participants with a known occupation from the second wave of the Nord-Trondelag Health Study (Helseundersokelsen i Nord-Trondelag 2 (HUNT2) 1995-1997), Norway. Complete information on emigration and death from all causes was obtained from the National Registries. We used the depression subscale of the Hospital Anxiety and Depression Scale (HADS) to measure symptoms of depression. We compared farmers to 4 other occupational groups. Our baseline study population comprised 32 618 participants. Statistical analyses were performed using the Cox proportional hazards models. RESULTS: The estimated mortality risk in farmers was lower than in all other occupations combined, with a sex and age-adjusted HR (0.91, 95% CI 0.82 to 1.00). However, farmers had an 11% increased age-adjusted and sex-adjusted mortality risk compared with the highest ranked socioeconomic group (HR 1.11, 95% CI 0.98 to 1.25). In farmers, symptoms of depression were associated with a 13% increase in sex-adjusted and age-adjusted mortality risk (HR 1.13, 95% CI 0.88 to 1.45). Compared with other occupations this was the lowest HR, also after adjusting for education, marital status, long-lasting limiting somatic illness and lifestyle factors (HR 1.08, 95% CI 0.84 to 1.39). CONCLUSIONS: Farmers had lower all-cause mortality compared with the other occupational groups combined. Symptoms of depression were associated with an increased mortality risk in farmers, but the risk increase was smaller compared with the other occupational groups. PMID- 27188812 TI - Prevalence and trends of sensitisation to aeroallergens in patients with allergic rhinitis in Guangzhou, China: a 10-year retrospective study. AB - OBJECTIVE: To investigate the prevalence and trends of sensitisation to common aeroallergens among outpatients with allergic rhinitis (AR) in Guangzhou, China, over the past decade. DESIGN: A retrospective study; linear-by-linear association and simple linear regression were used to determine the trends in the prevalence of aeroallergen sensitisation. SETTING: One grade-A hospital in Guangzhou, the largest city in southern China. PARTICIPANTS: A total of 5486 patients (2297 males and 2489 females) who visited the ear, nose and throat outpatient clinic, from January 2005 to December 2014, were enrolled. All patients who presented with nasal hyper-reactive symptoms and who completed serological allergy testing, measuring specific IgE (sIgE) in the serum, were included. Among them, 4085 participants (2269 males and 1816 females) were diagnosed as being patients with AR. OUTCOME MEASURES: Prevalence and trends of sensitisation to various types of aeroallergens were assessed. RESULTS: The overall prevalence of sIgE-mediated sensitisation to aeroallergens in these patients with AR were as follows: 84.4% for house dust mites (HDMs), 23.4% for pet allergens, 21.1% for cockroaches, 9.1% for mould allergens, 7.7% for tree pollen and 6.0% for weed pollen. When all patients with nasal hyper-reactivity were stratified by decade of age, increasing age was associated with a decrease in sIgE positivity by ~5.13% (95% CI -7.28% to -2.98%, p<0.01). Within the past decade, the prevalence of sensitisation to pet allergens in patients with AR increased at an annual rate of 1.3% (95% CI 0.85% to 1.67%, p<0.01). CONCLUSIONS: This study demonstrated that HDMs comprised the most common aeroallergen in Guangzhou. The prevalence of sensitisation to aeroallergens decreased with increasing age. During the past decade, the prevalence of sensitisation to pet allergens showed an upward trend, suggesting an urgent need for its prevention and treatment. PMID- 27188813 TI - A qualitative analysis of Maori and Pacific smokers' views on informed choice and smoking. AB - OBJECTIVES: Tobacco companies frame smoking as an informed choice, a strategy that holds individuals responsible for harms they incur. Few studies have tested this argument, and even fewer have examined how informed indigenous smokers or those from minority ethnicities are when they start smoking. We explored how young adult Maori and Pacific smokers interpreted 'informed choice' in relation to smoking. PARTICIPANTS: Using recruitment via advertising, existing networks and word of mouth, we recruited and undertook qualitative in-depth interviews with 20 Maori and Pacific young adults aged 18-26 years who smoked. ANALYSES: Data were analysed using an informed-choice framework developed by Chapman and Liberman. We used a thematic analysis approach to identify themes that extended this framework. RESULTS: Few participants considered themselves well informed and none met more than the framework's initial two criteria. Most reflected on their unthinking uptake and subsequent addiction, and identified environmental factors that had facilitated uptake. Nonetheless, despite this context, most agreed that they had made an informed choice to smoke. CONCLUSIONS: The discrepancy between participants' reported knowledge and understanding of smoking's risks, and their assessment of smoking as an informed choice, reflects their view of smoking as a symbol of adulthood. Policies that make tobacco more difficult to use in social settings could help change social norms around smoking and the ease with which initiation and addiction currently occur. PMID- 27188814 TI - Does n-3 LCPUFA supplementation during pregnancy increase the IQ of children at school age? Follow-up of a randomised controlled trial. AB - INTRODUCTION: Despite recommendations that pregnant women increase their docosahexaenoic acid (DHA) intake to support fetal brain development, a recent systematic review found a lack of high-quality data to support the long-term effects of DHA supplementation on children's neurodevelopment. METHODS AND ANALYSIS: We will assess child neurodevelopment at 7 years of age in follow-up of a multicentre double-blind randomised controlled trial of DHA supplementation in pregnancy. In 2010-2012, n=2399 Australian women with a singleton pregnancy <21 weeks' gestation were randomised to receive 3 capsules daily containing a total dose of 800 mg DHA/day or a vegetable oil placebo until birth. N=726 children from Adelaide (all n=97 born preterm, random sample of n=630 born at term) were selected for neurodevelopmental follow-up and n=638 (preterm n=85) are still enrolled at 7 years of age. At the 7-year follow-up, a psychologist will assess the primary outcome, IQ, with the Wechsler Abbreviated Scale of Intelligence, Second Edition. Specific measures of executive functioning (Fruit Stroop and the Rey Complex Figure), attention (Test of Everyday Attention for Children), memory and learning (Rey Auditory Verbal Learning Test), language (Clinical Evaluation of Language Fundamentals, Fourth Edition) and basic educational skills (Wide Range Achievement Test, Fourth Edition) will also be administered. Caregivers will be asked to complete questionnaires measuring behaviour and executive functioning. Families, clinicians and research personnel are blinded to group assignment with the exception of families who requested unblinding prior to the follow-up. All analyses will be conducted according to the intention-to-treat principal. ETHICS AND DISSEMINATION: All procedures will be approved by the relevant institutional ethics committees prior to start of the study. The results of this study will be disseminated in peer-reviewed journal publications and academic presentations. TRIAL REGISTRATION NUMBERS: ACTRN12605000569606 and ACTRN12614000770662. PMID- 27188816 TI - Polymer-Graphene Nanocomposite Materials for Electrochemical Biosensing. AB - Biosensing is an important and rapidly developing field, with numerous potential applications in health care, food processing, and environmental control. Polymer graphene nanocomposites aim to leverage the unique, attractive properties of graphene by combining them with those of a polymer matrix. Molecular imprinted polymers, in particular, offer the promise of artificial biorecognition elements. A variety of polymers, including intrinsically conducting polymers (polyaniline, polypyrrole), bio-based polymers (chitosan, polycatechols), and polycationic polymers (poly(diallyldimethylammonium chloride), polyethyleneimine), have been utilized as matrices for graphene-based nanofillers, yielding sensitive biosensors for various biomolecules, such as proteins, nucleic acids, and small molecules. PMID- 27188815 TI - Service factors causing delay in specialist assessment for TIA and minor stroke: a qualitative study of GP and patient perspectives. AB - OBJECTIVE: To understand how service factors contribute to delays to specialist assessment following transient ischaemic attack (TIA) or minor stroke. DESIGN: Qualitative study using semistructured interviews, analysis by constant comparison. SETTING: Leicester, UK. PARTICIPANTS: Patients diagnosed with TIA or minor stroke, at hospital admission or in a rapid-access TIA clinic (n=42), general practitioners (GPs) of participating patients if they had been involved in the patients' care (n=18). DATA: Accounts from patients and GPs of factors contributing to delay following action to seek help from a healthcare professional (HCP). RESULTS: The following categories of delay were identified. First, delay in assessment in general practice following contact with the service; this related to availability of same day appointments, and the role of the receptionist in identifying urgent cases. Second, delays in diagnosis by the HCP first consulted, including GPs, optometrists, out-of-hours services, walk-in centres and the emergency department. Third, delays in referral after a suspected diagnosis; these included variable use of the ABCD(2) (Age, Blood pressure, Clinical features, Duration, Diabetes) risk stratification score and referral templates in general practice, and referral back to the patients' GP in cases where he/she was not the first HCP consulted. CONCLUSIONS: Primary and emergency care providers need to review how they can best handle patients presenting with symptoms that could be due to stroke or TIA. In general practice, this may include receptionist training and/or triage by a nurse or doctor. Mechanisms need to be established to enable direct referral to the TIA clinic when patients whose symptoms have resolved present to other agencies. Further work is needed to improve diagnostic accuracy by non-specialists. PMID- 27188817 TI - Huntington disease. AB - Huntington disease is devastating to patients and their families - with autosomal dominant inheritance, onset typically in the prime of adult life, progressive course, and a combination of motor, cognitive and behavioural features. The disease is caused by an expanded CAG trinucleotide repeat (of variable length) in HTT, the gene that encodes the protein huntingtin. In mutation carriers, huntingtin is produced with abnormally long polyglutamine sequences that confer toxic gains of function and predispose the protein to fragmentation, resulting in neuronal dysfunction and death. In this Primer, we review the epidemiology of Huntington disease, noting that prevalence is higher than previously thought, geographically variable and increasing. We describe the relationship between CAG repeat length and clinical phenotype, as well as the concept of genetic modifiers of the disease. We discuss normal huntingtin protein function, evidence for differential toxicity of mutant huntingtin variants, theories of huntingtin aggregation and the many different mechanisms of Huntington disease pathogenesis. We describe the genetic and clinical diagnosis of the condition, its clinical assessment and the multidisciplinary management of symptoms, given the absence of effective disease-modifying therapies. We review past and present clinical trials and therapeutic strategies under investigation, including impending trials of targeted huntingtin-lowering drugs and the progress in development of biomarkers that will support the next generation of trials. For an illustrated summary of this Primer, visit: http://go.nature.com/hPMENh. PMID- 27188818 TI - Towards the minimal nitrogen-fixing symbiotic genome. AB - diCenzo and coworkers have reverse engineered a rhizobium into a non-nitrogen fixer, creating a genomic platform for gain-of-function genetics studies, which should aid to identify the minimal nitrogen fixing symbiotic genome. PMID- 27188819 TI - Gut microbiota: How to build healthy growth-promoting gut communities. PMID- 27188820 TI - Gut microbiota: FMT - enduring strains. PMID- 27188821 TI - IBD: Dysbiosis underlies CARD9 risk alleles in colitis. PMID- 27188822 TI - Pancreatic cancer: A multipronged approach to pancreatic cancer treatment. PMID- 27188824 TI - Granular cell tumors in the central nervous system: a report on eight cases and a literature review. AB - OBJECTIVE: Granular cell tumors (GCTs) in the central nervous system (CNS) are extremely rare. We report here a series of eight GCTs at various locations in the CNS and provide a full review of the published literature. METHODS: Eight patients with pathologically confirmed GCT in the CNS were retrospectively reviewed. The patients were followed up via telephone interview or an outpatient department. RESULTS: Five patients were female, and three were male. Of the eight tumors, three were located at the sellar region, two were located in the spinal canal, one was located at the cerebral hemisphere, one was parasellar-nasal communicating, and one was combined with an enterogenous cyst at the ventral aspect of the medulla oblongata. Six patients were symptomatic, and two patients were found incidentally. Most GCTs tended to be homogeneous and well defined on radiological images. The parasellar-nasal communicating GCT showed destruction of the skull base and an evident cystic component in the sphenoid sinus. The various GCTs had similar histological features, and they tended to be histologically benign. Most tumors did not recur after the operation. After subtotal resection, one residual spinal GCT regrew during the follow-up period. The patient with the parasellar-nasal communicating GCT developed progressive visual loss in the right eye after the operation; and she received adjuvant radiation therapy. CONCLUSION: GCTs at different locations in the CNS can have significantly different clinical features and should be considered distinct entities. Except for the granular cell astrocytoma (GCA), most GCTs in the CNS tended to be benign. Malignant GCTs are rare and difficult to treat. PMID- 27188825 TI - Blood parasites in hooded crows (Corvus corone cornix) in Northwest Italy. AB - Haemoparasites and their effects on hooded crows (Corvus corone cornix) are poorly studied. The aims are to evaluate the prevalence of Haemoproteus spp./Plasmodium spp. or Leucocytozoon spp., to correlate this with gross and histopathological findings, and to investigate the association among infection and geographical origin, age, gender, parasite distribution and prevalence among organs. Hooded crows (n = 47) were collected within a regional culling programme from 3 districts in the province of Turin (Italy) and subjected to necropsy. Histological and molecular analyses were carried out on some tissues. Leucocytozoon spp. was detected in 46 crows (97.9%) by polymerase chain reaction (PCR), whereas 28 birds (59.6%) were found to be positive for Haemoproteus spp./Plasmodium spp. The distribution of parasites in several organs varied significantly, showing that Leucocytozoon spp. is ubiquitous in organs in contrast with Haemoproteus spp./Plasmodium spp., which have a specific predilection for spleen and lungs. The prevalence of Haemoproteus spp./Plasmodium spp. also differed significantly among the crows captured in the areas of the study. The high prevalence of haemoparasites emphasizes the success of ornithophilic vectors and the susceptibility of this species to infection. Differences in prevalence among the sites are probably due to orographic features of the areas, variations in vector species and density, or to crow population size or structure. In spite of the high infection rate, no gross and histological lesions were found. This finding further suggests an evolutionary adaptation between crows and avian blood parasites. PMID- 27188826 TI - Survey on intestinal helminth fauna of woodcocks (Scolopax rusticola) in Italy. AB - Every year populations of the European woodcock (Scolopax rusticola) migrate from Central and Northern Europe to the Mediterranean basin. South of Italy is one of the most common wintering site for this species. Given that information on parasites of woodcocks is scarce, the present study aimed at identifying the parasitic species affecting woodcocks migrating in Italy. The gastrointestinal tract of 206 woodcocks hunted in Southern Italy was removed and examined for parasites. From each animal a faecal sample was analysed by flotation test. The necropsy showed the presence of cestodes, i.e. Paricterotaenia paradoxa (59.4%) and Aploparaksis filum (49.5%), and of acanthocephalan Prosthorhynchus scolopacidis (22.4%). In one bird we also detected Parastrigea robusta, which is a trematode until now reported only in mallards (Anas platyrhynchos). Mixed infections (i.e., polyspecific infections) were detected in 53 (27.6%) animals. The most common were those caused by A. filum and P. paradoxa (12.5%), and by P. paradoxa and P. scolopacidis (8.3%). Copromicroscopic examinations revealed the presence of eggs belonging to nematodes Syngamus spp. (1.94%) in 4 woodcocks and of eggs of cestodes Aploparaksis spp. (37.86%) in 78 woodcocks. The present results fill a gap in the knowledge on parasites affecting woodcocks. PMID- 27188823 TI - Alcohol: taking a population perspective. AB - Alcohol consumption is a global phenomenon, as is the resultant health, social and economic harm. The nature of these harms varies with different drinking patterns and with the societal and political responses to the burden of harm; nevertheless, alcohol-related chronic diseases have a major effect on health. Strong evidence exists for the effectiveness of different strategies to minimize this damage and those policies that target price, availability and marketing of alcohol come out best, whereas those using education and information are much less effective. However, these policies can be portrayed as anti-libertarian and so viewing them in the context of alcohol-related harm to those other than the drinker, such as the most vulnerable in society, is important. When this strategy is successful, as in Scotland, it has been possible to pass strong and effective legislation, such as for a minimum unit price for alcohol. PMID- 27188827 TI - Diets of deepwater oreos (Oreosomatidae) and orange roughy Hoplostethus atlanticus. AB - The diets of black oreo Allocyttus niger, smooth oreo Pseudocyttus maculatus, spiky oreo Neocyttus rhomboidalis and orange roughy Hoplostethus atlanticus were determined from examination of contents of 240, 311, 76 and 415 non-empty stomachs, from fishes sampled by bottom trawl on Chatham Rise to the east of South Island, New Zealand. Hoplostethus atlanticus had an opportunistic predatory strategy with a broad diet dominated by prawns and mesopelagic teleosts, but with substantial components of mysids and cephalopods. Pseudocyttus maculatus was strongly specialized on gelatinous zooplankton (jellyfish and salps). Allocyttus niger consumed mainly salps and hyperiid amphipods, and to a lesser extent fishes, prawns, mysids and copepods. Neocyttus rhomboidalis primarily consumed salps, along with mysids, euphausiids and fishes. Only P. maculatus did not exhibit significant ontogenetic variation in diet. The diets were also influenced by year and bottom depth. Differences in the distributions and diets of the four species probably reduce conflicts in resource use. PMID- 27188828 TI - History repeating itself: Arnaud's case of pathological deja vu. AB - We present a translation of Arnaud's (1896) case report of Patient Louis, a case he describes as having a pathological form of deja vu. Louis has the delusional belief that the present moment is a repetition of an exact same previous event. Arnaud's paper is critical for two reasons. Firstly, it is amongst the first articles in the scientific literature to describe the deja vu experience using the term 'deja vu'. Secondly, the case report of someone with delusional and persistent deja vu, anticipates recently reported cases with similar symptoms, which are beginning to gain interest as a particular form of memory disorder. We offer a contemporary analysis of Louis and conclude that, whilst the article was critical in the development of deja vu as a scientific concern, Louis's distorted memory is not best described as deja vu, but rather as a form of reduplicative paramnesia described as recollective confabulation. PMID- 27188829 TI - Topological distortion and reorganized modular structure of gut microbial co occurrence networks in inflammatory bowel disease. AB - The gut microbiome plays a key role in human health, and alterations of the normal gut flora are associated with a variety of distinct disease states. Yet, the natural dependencies between microbes in healthy and diseased individuals remain far from understood. Here we use a network-based approach to characterize microbial co-occurrence in individuals with inflammatory bowel disease (IBD) and healthy (non-IBD control) individuals. We find that microbial networks in patients with IBD differ in both global structure and local connectivity patterns. While a "core" microbiome is preserved, network topology of other densely interconnected microbe modules is distorted, with potent inflammation mediating organisms assuming roles as integrative and highly connected inter modular hubs. We show that while both networks display a rich-club organization, in which a small set of microbes commonly co-occur, the healthy network is more easily disrupted by elimination of a small number of key species. Further investigation of network alterations in disease might offer mechanistic insights into the specific pathogens responsible for microbiome-mediated inflammation in IBD. PMID- 27188831 TI - The phonological neighbourhood effect on short-term memory for order. AB - There is a growing body of literature that suggests that long-term memory (LTM) and short-term memory (STM) structures that were once thought to be distinct are actually co-dependent, and that LTM can aid retrieval from STM. The mechanism behind this effect is commonly argued to act on item memory but not on order memory. The aim of the current study was to examine whether LTM could exert an influence on STM for order by examining an effect attributed to LTM, the phonological neighbourhood effect, in a task that reduced the requirement to retain item information. In Experiment 1, 18 participants completed a serial reconstruction task where neighbourhood density alternated within the lists. In Experiment 2, 22 participants completed a serial reconstruction task using pure lists of dense and sparse neighbourhood words. In Experiment 3, 22 participants completed a reconstruction task with both mixed and pure lists. There was a significant effect of neighbourhood density with better recall for dense than sparse neighbourhood words in pure lists but not in mixed lists. Results suggest that LTM exerts an influence prior to that proposed by many models of memory for order. PMID- 27188833 TI - CORR Insights((r)): How Often Does Spindle Failure Occur in Compressive Osseointegration Endoprostheses for Oncologic Reconstruction? PMID- 27188832 TI - A Prognostic Model of Surgical Site Infection Using Daily Clinical Wound Assessment. AB - BACKGROUND: Surgical site infection (SSI) remains a common, costly, and morbid health care-associated infection. Early detection can improve outcomes, yet previous risk models consider only baseline risk factors (BF) not incorporating a proximate and timely data source-the wound itself. We hypothesize that incorporation of daily wound assessment improves the accuracy of SSI identification compared with traditional BF alone. STUDY DESIGN: A prospective cohort of 1,000 post open abdominal surgery patients at an academic teaching hospital were examined daily for serial features (SF), for example, wound characteristics and vital signs, in addition to standard BF, for example, wound class. Using supervised machine learning, we trained 3 Naive Bayes classifiers (BF, SF, and BF+SF) using patient data from 1 to 5 days before diagnosis to classify SSI on the following day. For comparison, we also created a simplified SF model that used logistic regression. Control patients without SSI were matched on 5 similar consecutive postoperative days to avoid confounding by length of stay. Accuracy, sensitivity/specificity, and area under the receiver operating characteristic curve were calculated on a training and hold-out testing set. RESULTS: Of 851 patients, 19.4% had inpatient SSIs. Univariate analysis showed differences in C-reactive protein, surgery duration, and contamination, but no differences in American Society of Anesthesiologists scores, diabetes, or emergency surgery. The BF, SF, and BF+SF classifiers had area under the receiver operating characteristic curves of 0.67, 0.76, and 0.76, respectively. The best performing classifier (SF) had optimal sensitivity of 0.80, specificity of 0.64, positive predictive value of 0.35, and negative predictive value of 0.93. Features most associated with subsequent SSI diagnosis were granulation degree, exudate amount, nasogastric tube presence, and heart rate. CONCLUSIONS: Serial features provided moderate positive predictive value and high negative predictive value for early identification of SSI. Addition of baseline risk factors did not improve identification. Features of evolving wound infection are discernable before the day of diagnosis, based primarily on visual inspection. PMID- 27188834 TI - CORR Insights(r): A Novel System for the Surgical Staging of Primary High-grade Osteosarcoma: The Birmingham Classification. PMID- 27188837 TI - When evidence is not enough: a case study on alcohol marketing legislation in Brazil. AB - AIMS: This case study identifies the influence and mechanisms that the alcohol industry in Brazil has been able to bring to bear to maintain self-regulation in the marketing of beer and many wines set against a trend of increasing alcohol consumption in Brazil, particularly among young people and women. It identifies the forms of power and strategies used by the alcohol industry in Brazil that may be useful for other countries to consider in seeking to move from self-regulation to state regulation of alcohol marketing. METHOD: A review was conducted of recent legal documents and court cases, as well as the activities of alcoholic beverage industries. RESULTS: Because of an exemption, Brazilian law had established that both beer and many wines are not alcoholic beverages for marketing purposes. These beverages are subjected to industry self-regulation codes. Research shows that beer and wine marketing often violates industry codes, with little or no enforcement of penalties for non-compliance. Attempts to include beer and wine in the legal definition of alcohol have been opposed by the alcohol industry, and the courts have delegated responsibility to the legislature. The recent legal activities surrounding alcohol sales during the 2014 World Cup games in Brazil provide evidence of the alcohol industry's influence on the legislative process. CONCLUSION: The alcohol industry in Brazil plays a significant role in the formulation of public policies on alcohol, especially regarding the regulation of marketing. This power is exercised by strong lobbying of government officials responsible for public policies. PMID- 27188836 TI - Early Subsidence Predicts Failure of a Cemented Femoral Stem With Minor Design Changes. AB - BACKGROUND: Radiostereometry (RSA) measurements of early micromotion can predict later failure in hip and knee prostheses. In hip implants, RSA has been particularly helpful in the evaluation of composite-beam stem designs. The Spectron EF Primary stem (Smith & Nephew, London, UK) has shown inferior performance compared with its predecessors in both clinical studies and registry reports. Early RSA studies have shown somewhat greater subsidence for the Spectron EF Primary stem compared with the earlier Spectron EF, but still within boundaries considered to be safe. QUESTIONS/PURPOSES: Our primary research question was whether stem subsidence and rotation for this stem design measured with RSA at 2 years can predict later stem failure. A secondary question was whether high femoral stem offset and small stem sizes, both features specific to the Spectron EF Primary stem compared with its predecessors, are associated with stem failure rate. METHODS: Two hundred forty-seven hips (209 patients with median age 63 years [range, 29-80 years], 65% female, and 77% primary osteoarthritis) with a valid RSA examination at 2 years were selected from four different RSA studies (totaling 279 hips in 236 patients) in our department. The studies were primarily aimed at evaluating cup fixation, bone cement, and polyethylene types. All study patients received a cemented Spectron EF Primary stem. The selected hips had complete followup until stem failure, death, or the end of the followup period. Stem failure was defined as revision of a loose femoral stem or radiological failure with significant osteolysis in Gruen zones 2 to 6. Cox regression analyses were performed to evaluate if stem subsidence and rotation after 2 years, adjusted for age, sex, stem size, standard/high stem offset, and conventional/highly crosslinked polyethylene, could predict later clinical aseptic failure of the stem. We identified 32 stem failures (27 revisions, five radiological failures) at 14 years median followup (range, 3-18 years). Ten-year stem survival was 94% (95% confidence interval [CI], 90%-96%). RESULTS: Stem subsidence at 2 years (adjusted hazard ratio [HR], 6.0; 95% CI, 2.5 15; p < 0.001) and retrotorsion of the stem (adjusted HR, 1.7; 95% CI, 1.1-2.5; p = 0.018) were associated with later stem failure. Further risk factors were male sex (subsidence analysis HR, 6.9; p > 0.001), use of the two smallest stem sizes (HRsize 1, 8.0; p > 0.001, HRsize 2, 1 [reference], HRsize 3+, 0.06; p = 0.035), and the high offset option (HR, 3.1; p = 0.005). CONCLUSIONS: Stem subsidence and retrotorsion at 2 years can predict later failure in the Spectron EF Primary stem, consistent with earlier findings on composite-beam cemented stems. Small stem size and high-offset stems comprise the main group of underperforming stems. We recommend that premarket small-scale RSA studies be performed after any design change to a THA femoral component, because even seemingly minor design changes may unexpectedly result in inferior performance. LEVEL OF EVIDENCE: Level III, therapeutic study. PMID- 27188830 TI - Acute rheumatic fever and rheumatic heart disease. AB - Acute rheumatic fever (ARF) is the result of an autoimmune response to pharyngitis caused by infection with group A Streptococcus. The long-term damage to cardiac valves caused by ARF, which can result from a single severe episode or from multiple recurrent episodes of the illness, is known as rheumatic heart disease (RHD) and is a notable cause of morbidity and mortality in resource-poor settings around the world. Although our understanding of disease pathogenesis has advanced in recent years, this has not led to dramatic improvements in diagnostic approaches, which are still reliant on clinical features using the Jones Criteria, or treatment practices. Indeed, penicillin has been the mainstay of treatment for decades and there is no other treatment that has been proven to alter the likelihood or the severity of RHD after an episode of ARF. Recent advances - including the use of echocardiographic diagnosis in those with ARF and in screening for early detection of RHD, progress in developing group A streptococcal vaccines and an increased focus on the lived experience of those with RHD and the need to improve quality of life - give cause for optimism that progress will be made in coming years against this neglected disease that affects populations around the world, but is a particular issue for those living in poverty. PMID- 27188835 TI - Poor Survivorship and Frequent Complications at a Median of 10 Years After Metal on-Metal Hip Resurfacing Revision. AB - BACKGROUND: High short-term failure rates have been reported for several metal-on metal hip resurfacing (MoMHR) designs. Early observations suggested that MoMHRs revised to total hip arthroplasties (THAs) for pseudotumor had more major complications and inferior patient-reported outcomes compared with other revision indications. However, little is known about implant survivorship and patient reported outcomes at more than 5 years after MoMHR revision. QUESTIONS/PURPOSES: (1) What are the implant survivorship, proportion of complications and abnormal radiological findings, and patient-reported outcomes at a median of 10 years after MoMHR revision surgery? (2) Are survivorship, complications, and patient reported outcomes influenced by revision indication? (3) Do any other factors predict survivorship, complications, and patient-reported outcomes? METHODS: Between 1999 and 2008, 53 MoMHR revision procedures in 51 patients (mean age, 55 years; 62% female) were performed at one center and were all included in this retrospective study. Two patients (4%) were lost to followup and two patients (4%) died before a minimum followup of 7 years (median, 10.3 years; range 7-15 years). Revision indications included pseudotumor (n = 16), femoral neck fracture (n = 21), and other causes (n = 16). In most cases (62%, n = 33) both components were revised to a non-MoM bearing THA with the remainder (38%, n = 20: fracture, loosening, or head collapse) undergoing femoral-only revision to a large-diameter MoM THA. Postrevision complications, rerevision, Oxford Hip Score (OHS), and UCLA score were determined using both a longitudinally maintained institutional database and postal questionnaire. Implant survivorship was assessed using the Kaplan-Meier method (endpoint was rerevision surgery). Radiographs at latest followup were systematically assessed for any signs of failure (loosening, migration, osteolysis) by one observer blinded to all clinical information and not involved in the revision procedures. RESULTS: Overall, 45% (24 of 53) experienced complications and 38% (20 of 53) underwent rerevision. Ten-year survival free from rerevision for revised MoMHRs was 63% (95% confidence interval [CI], 48%-74%). Revision indications were not associated with differences in the frequency of complications or repeat revisions. With the numbers available, 10 year survival free from rerevision for pseudotumor revisions (56%; 95% CI, 30% 76%) was not different from the fracture (68%; 95% CI, 42%-85%; p = 0.359) and other groups (63%; 95% CI, 35%-81%; p = 0.478). Pseudotumor revisions had inferior OHSs (median, 21; range, 2-46; p = 0.007) and UCLA scores (median, 2; range, 2-7; p = 0.0184) compared with fracture and other revisions. Ten-year survival free from rerevision after femoral-only revision using another large diameter MoM bearing was lower (p = 0.0498) compared with all component revisions using non-MoM bearings. After controlling for potential confounding variables such as age, sex, and revision indication, we found femoral-only revision as the only factor predicting rerevision (hazard ratio, 5.7; 95% CI, 1.1-29; p = 0.040). CONCLUSIONS: Poor implant survivorship and frequent complications were observed at a median of 10 years after MoMHR revision. However, patients undergoing femoral-only revisions with large-diameter MoM bearings had the worst survivorship, whereas patients revised for pseudotumor had the most inferior patient-reported outcomes. Our findings suggest these two patient subgroups require regular surveillance after MoMHR revision. LEVEL OF EVIDENCE: Level III, therapeutic study. PMID- 27188838 TI - Design, synthesis and in vitro splicing inhibition of desmethyl and carba derivatives of herboxidiene. AB - Herboxidiene is a potent inhibitor of spliceosomes. It exhibits excellent anticancer activity against multiple human cancer cell lines. Herein, we describe an enantioselective synthesis of a desmethyl derivative and the corresponding carba-derivatives of herboxidiene. The synthesis involved Suzuki coupling of a vinyl iodide with boronate as the key reaction. For the synthesis of carba derivatives, the corresponding optically active cyclohexane-1,3-dicarbonyl derivatives were synthesized using an enantioselective desymmetrization of meso anhydride. The biological properties of these derivatives were evaluated in an in vitro splicing assay. PMID- 27188839 TI - Successful intestinal Echinococcus multilocularis oncosphere invasion and subsequent hepatic metacestode establishment in resistant RccHanTM:WIST rats after pharmacological immunosuppression. AB - Susceptibility/resistance to larval Echinococcus multilocularis infection varies greatly depending on host species and strains. Whereas several mice strains and non-human primates are highly susceptible to alveolar echinococcosis, rats and most of humans are considered as more resistant. In this study, we aimed to elucidate factors responsible for host resistance in rats (Experiments A-D). (A) The parasite establishment was not observed in immunocompetent Wistar rats orally inoculated with sodium hypochlorite resistant eggs with/without pig bile, or activated/non-activated oncospheres (NAO). Peritoneal inoculation with NAO or metacestode tissue allowed the parasite establishment in rats. (B) T-cell deficient athymic nude rats showed complete resistance against the metacestode establishment after oral inoculation with parasite eggs. This finding suggests that T-cell-independent parasite clearance occurred in the animals during early phase of the parasite invasion. Finally, Wistar rats that received pharmacological immunosuppression using either dexamethasone (DMS) alone or methotrexate (MTX) i.p. alone or a combination of these compounds were orally inoculated with the parasite's eggs. As a result (D), successful establishment of metacestode with protoscoleces was observed in all 3 rats treated with DMS (s.c.) alone or in all 6 rats treated with DMS (s.c.) plus MTX but not in 8 rats with MTX alone, suggesting that factors affected by DMS treatment are responsible to regulate the parasite invasion and establishment. PMID- 27188840 TI - Challenges in Rare Variant Association Studies for Complex Kidney Traits: CFHR5 and IgA Nephropathy. PMID- 27188841 TI - Sex Differences and Renal Protection: Keeping in Touch with Your Feminine Side. PMID- 27188842 TI - Coordinated Control of ENaC and Na+,K+-ATPase in Renal Collecting Duct. AB - Tubular reabsorption of filtered sodium is tightly controlled to maintain body volume homeostasis. The rate of sodium transport by collecting duct (CD) cells varies widely in response to dietary sodium intake, GFR, circulating hormones, neural signals, and local regulatory factors. Reabsorption of filtered sodium by CD cells occurs via a two-step process. First, luminal sodium crosses the apical plasma membrane along its electrochemical gradient through epithelial sodium channels (ENaC). Intracellular sodium is then actively extruded into the interstitial space by the Na(+),K(+)-ATPase located along the basolateral membrane. Mismatch between sodium entry and exit induces variations in sodium intracellular concentration and cell volume that must be maintained within narrow ranges for control of vital cell functions. Therefore, renal epithelial cells display highly coordinated apical and basolateral sodium transport rates. We review evidence from experiments conducted in vivo and in cultured cells that indicates aldosterone and vasopressin, the two major hormones regulating sodium reabsorption by CD, generate a coordinated stimulation of apical ENaC and basolateral Na(+),K(+)-ATPase. Moreover, we discuss evidence suggesting that variations in sodium entry per se induce a coordinated change in Na(+),K(+) ATPase activity through the signaling of protein kinases such as protein kinase A and p38 mitogen-activated protein kinase. PMID- 27188844 TI - Relief from detrimental consequences of chronic psychosocial stress in mice deficient for the metabotropic glutamate receptor subtype 7. AB - Chronic stress-related psychiatric conditions and comorbid somatic pathologies are an enormous public health concern in modern society. The etiology of these disorders is complex, with stressors holding a chronic and psychosocial component representing the most acknowledged risk factor. During the last decades, research on the metabotropic glutamate receptor (mGlu) system advanced dramatically and much attention was given to the role of the metabotropic glutamate receptor subtype 7 (mGlu7) in acute stress-related behavior and physiology. However, virtually nothing is known about the potential involvement of mGlu7 in chronic psychosocial stress-related conditions. Using the chronic subordinate colony housing (CSC, 19 days) in male mice, we addressed whether central mGlu7 is altered upon chronic psychosocial stressor exposure and whether genetic ablation of mGlu7 interferes with the multitude of chronic stress-induced alterations. CSC exposure resulted in a downregulation of mGlu7 mRNA transcript levels in the prefrontal cortex, a brain region relevant for stress-related behaviors and physiology. Interestingly, mGlu7 deficiency relieved multiple chronic stress induced alterations including the CSC-induced anxiety-prone phenotype; mGlu7 ablation also ameliorated CSC-induced physiological and immunological consequences such as hypothalamo-pituitary-adrenal (HPA) axis dysfunctions and colonic inflammation, respectively. Together, our findings provide first evidence for the involvement of mGlu7 in a wide range of behavioral and physiological alterations in response to chronic psychosocial stressor exposure. Moreover, the stress-protective phenotype of genetic mGlu7 ablation suggests mGlu7 pharmacological blockade to be a relevant option for the treatment of chronic stress-related emotional and somatic dysfunctions. This article is part of the Special Issue entitled 'Metabotropic Glutamate Receptors, 5 years on'. PMID- 27188843 TI - Blood coagulation factor XII drives adaptive immunity during neuroinflammation via CD87-mediated modulation of dendritic cells. AB - Aberrant immune responses represent the underlying cause of central nervous system (CNS) autoimmunity, including multiple sclerosis (MS). Recent evidence implicated the crosstalk between coagulation and immunity in CNS autoimmunity. Here we identify coagulation factor XII (FXII), the initiator of the intrinsic coagulation cascade and the kallikrein-kinin system, as a specific immune cell modulator. High levels of FXII activity are present in the plasma of MS patients during relapse. Deficiency or pharmacologic blockade of FXII renders mice less susceptible to experimental autoimmune encephalomyelitis (a model of MS) and is accompanied by reduced numbers of interleukin-17A-producing T cells. Immune activation by FXII is mediated by dendritic cells in a CD87-dependent manner and involves alterations in intracellular cyclic AMP formation. Our study demonstrates that a member of the plasmatic coagulation cascade is a key mediator of autoimmunity. FXII inhibition may provide a strategy to combat MS and other immune-related disorders. PMID- 27188845 TI - Physiological maturation and drug responses of human induced pluripotent stem cell-derived cortical neuronal networks in long-term culture. AB - The functional network of human induced pluripotent stem cell (hiPSC)-derived neurons is a potentially powerful in vitro model for evaluating disease mechanisms and drug responses. However, the culture time required for the full functional maturation of individual neurons and networks is uncertain. We investigated the development of spontaneous electrophysiological activity and pharmacological responses for over 1 year in culture using multi-electrode arrays (MEAs). The complete maturation of spontaneous firing, evoked responses, and modulation of activity by glutamatergic and GABAergic receptor antagonists/agonists required 20-30 weeks. At this stage, neural networks also demonstrated epileptiform synchronized burst firing (SBF) in response to pro convulsants and SBF suppression using clinical anti-epilepsy drugs. Our results reveal the feasibility of long-term MEA measurements from hiPSC-derived neuronal networks in vitro for mechanistic analyses and drug screening. However, developmental changes in electrophysiological and pharmacological properties indicate the necessity for the international standardization of culture and evaluation procedures. PMID- 27188847 TI - In vivo dosimetry using Gafchromic films during pelvic intraoperative electron radiation therapy (IOERT). AB - OBJECTIVE: To characterize in vivo dose distributions during pelvic intraoperative electron radiation therapy (IOERT) for rectal cancer and to assess the alterations introduced by irregular irradiation surfaces in the presence of bevelled applicators. METHODS: In vivo measurements were performed with Gafchromic films during 32 IOERT procedures. 1 film per procedure was used for the first 20 procedures. The methodology was then optimized for the remaining 12 procedures by using a set of 3 films. Both the average dose and two-dimensional dose distributions for each film were determined. Phantom measurements were performed for comparison. RESULTS: For flat and concave surfaces, the doses measured in vivo agree with expected values. For concave surfaces with step-like irregularities, measured doses tend to be higher than expected doses. Results obtained with three films per procedure show a large variability along the irradiated surface, with important differences from expected profiles. These results are consistent with the presence of surface hotspots, such as those observed in phantoms in the presence of step-like irregularities, as well as fluid build-up. CONCLUSION: Clinical dose distributions in the IOERT of rectal cancer are often different from the references used for prescription. Further studies are necessary to assess the impact of these differences on treatment outcomes. In vivo measurements are important, but need to be accompanied by accurate imaging of positioning and irradiated surfaces. ADVANCES IN KNOWLEDGE: These results confirm that surface irregularities occur frequently in rectal cancer IOERT and have a measurable effect on the dose distribution. PMID- 27188846 TI - Imaging follow-up after liver transplantation. AB - Liver transplantation (LT) represents the best treatment for end-stage chronic liver disease, acute liver failure and early stages of hepatocellular carcinoma. Radiologists should be aware of surgical techniques to distinguish a normal appearance from pathological findings. Imaging modalities, such as ultrasound, CT and MR, provide for rapid and reliable detection of vascular and biliary complications after LT. The role of imaging in the evaluation of rejection and primary graft dysfunction is less defined. This article illustrates the main surgical anastomoses during LT, the normal appearance and complications of the liver parenchyma and vascular and biliary structures. PMID- 27188848 TI - A novel RNAseq-assisted method for MHC class I genotyping in a non-model species applied to a lethal vaccination-induced alloimmune disease. AB - BACKGROUND: MHC class I genotyping is essential for a wide range of biomedical, immunological and biodiversity applications. Whereas in human a comprehensive MHC class I allele catalogue is available, respective data in non-model species is scarce in spite of decades of research. RESULTS: Taking advantage of the new high throughput RNA sequencing technology (RNAseq), we developed a novel RNAseq assisted method (RAMHCIT) for MHC class I typing at nucleotide level. RAMHCIT is performed on white blood cells, which highly express MHC class I molecules enabling reliable discovery of new alleles and discrimination of closely related alleles due to the high coverage of alleles with reads. RAMHCIT is more comprehensive than previous methods, because no targeted PCR pre-amplification of MHC loci is necessary, which avoids preselection of alleles as usually encountered, when amplification with MHC class I primers is performed prior to sequencing. In addition to allele identification, RAMHCIT also enables quantification of MHC class I expression at allele level, which was remarkably consistent across individuals. CONCLUSIONS: Successful application of RAMHCIT is demonstrated on a data set from cattle with different phenotype regarding a lethal, vaccination-induced alloimmune disease (bovine neonatal pancytopenia), for which MHC class I alleles had been postulated as causal agents. PMID- 27188850 TI - Amyotrophic Lateral Sclerosis in Northern Spain 40 Years Later: What Has Changed? AB - BACKGROUND: In the last years different studies have reported an increase of amyotrophic lateral sclerosis (ALS) incidence, highlighting the role of the environment in this disease. This prompted us to review ALS cases diagnosed at our hospital in the last decade and to compare them with a previous ALS series reported in our region 30 years ago. METHODS: We reviewed those ALS cases diagnosed at our centre between 2004 and 2013. Subsequently, we compared them with the previous series regarding clinical and epidemiological features. RESULTS: A total of 53 patients (30 males, 23 females) were included. The annual incidence was 1.7 cases per 100,000 inhabitants (2.2 and 1.2 per 100,000 in males and females, respectively), which was significantly higher than in the previous series (1 case per 100,000 inhabitants). Otherwise, the clinical and epidemiological features were similar in both series. The median age at symptom onset was 67 years, with a median diagnosis delay of 6 months. About two thirds of the patients presented with systemic ALS, whereas the remaining had a bulbar onset. Weakness, dysphagia, and dysarthria were the most common clinical symptoms at diagnosis. The median survival from symptom onset was 22 months. CONCLUSION: After 3 decades, the annual incidence of ALS has almost doubled in our region. We did not find significant differences regarding other clinical or epidemiological features. PMID- 27188849 TI - Altered Cyclooxygenase-2 Expression in Pulmonary Sarcoidosis is not Related to Clinical Classifications. AB - Elevated COX-2 activity is associated with the development of chronic lung diseases leading to bronchial obstruction, including sarcoidosis. The aim of the study was to examine expression pattern of COX-2 messenger RNA (mRNA). Expression was performed by q-PCR method in bronchoalveolar lavage (BAL) cells and peripheral blood (PB) lymphocytes in sarcoidosis patients (n = 61) and control group (n = 30). Analysis of COX-2 mRNA expression level in BAL fluid and PB revealed downregulation in sarcoidosis and control groups. In PB lymphocytes, the statistically significant difference between patients and controls was observed (P = 0.003, Mann-Whitney U test), with higher expression in patients. There were no statistically significant differences between patients without and with parenchymal involvement (stages I vs. II-IV), between patients with acute vs. insidious onset of disease and between patients with abnormal vs. normal spirometry (P > 0.05, Mann-Whitney U test). Results suggest that expression of COX-2 mRNA in patients with pulmonary sarcoidosis is not related to clinical classifications. PMID- 27188852 TI - Risk factors in ectopic pregnancy and differences between adults and adolescents, is consanguinity important? AB - The aim of the study was to determine the risk factors of ectopic pregnancy (EP) and to compare them between women over and under 20 years of age. 308 cases of EP (case group) were compared with 616 cases of normal pregnancy. Smoking [Ad OR =5.7 (CI 95%=2.8-11.6), p < 0.001], previous EP [Ad OR= 11.4 (CI 95%=3-42.4), p = 0.000], previous STD [Ad OR =3.2 (CI 95%=2.1-4.9), p < 0.001], previous use of IUD [Ad OR =4.1 (CI 95%=2.1-8), p < 0.001], history of infertility [Ad OR= 1.8 (CI 95%=1.1-3), p = 0.01], previous caesarean delivery [Ad OR= 1.5 (CI 95%=1.1 2.3), p = 0.03] and consanguinity [Ad OR =2.2 (CI 95%=1.3-3.6), p = 0.002] were considered as risk factors for EP. Prior abortion [p = 0.000], prior STD [p = 0.004], previous caesarean delivery [p = 0.000] and consanguinity [p = 0.04] were more in the >20-year-old group. Negative Rh [p = 0.02], good economic status [p = 0.000] and prior STD [p = 0.03] were more common in Afghan women. However, previous caesarean delivery [p = 0.04] was more in Iranian women. Smoking, previous EP, history of STD, IUD, infertility, previous caesarean delivery and consanguinity are all risk factors for EP. PMID- 27188853 TI - A novel strategy to enhance the luminescence performance of NaGdF4:Ln(3+) nanocrystals. AB - Promoting excitation efficiency is a direct route to enhance the luminescence properties of lanthanide doped materials. Here, we describe a novel strategy to enhance the luminescence performance of NaGdF4:Ln(3+) (Ln = Tb, Eu, Dy) nanoparticles by surface modification with benzoate (BA) and 1,10-phenanthroline (Phen) ligands via the sensitization of surface dopants. It was found that the surface ligands provide a new path for energy transfer to the activators due to the matching in energy levels between the two. Moreover, the overlap in excitation peaks for both Gd(3+) ions and ligands ensures the simultaneous energy transfer of Gd(3+)-> Ln(3+) and ligands -> Ln(3+) under a single wavelength excitation. The obtained NaGdF4 nanocomposite was characterized in detail using XRD, FT-IR, TGA, SEM, and EDS. The luminescence performance of the surface modified NaGdF4:Ln(3+) nanoparticles was also optimized by tuning the loading amount of modified ligands. In addition, luminescence thermometry was realized by monitoring emission intensity at different temperatures. PMID- 27188851 TI - Chiral amino acid metabolomics for novel biomarker screening in the prognosis of chronic kidney disease. AB - D-Amino acids, the enantiomers of L-amino acids, are increasingly recognized as novel biomarkers. Although the amounts of D-amino acids are usually very trace in human, some of them have sporadically been detected in blood from patients with kidney diseases. This study examined whether multiple chiral amino acids would be associated with kidney functions, comorbidities, and prognosis of chronic kidney disease (CKD) by enantioselective analyses of all chiral amino acids with a micro two-dimensional high-performance liquid chromatograph (2D-HPLC)-based analytical platform. 16 out of 21 D-amino acids were detected in plasma from 108 CKD patients in a longitudinal cohort. The levels of D-Ser, D-Pro, and D-Asn were strongly associated with kidney function (estimated glomerular filtration ratio), the levels of D-Ala and D-Pro were associated with age, and the level of D-Asp and D-Pro were associated with the presence of diabetes mellitus. D-Ser and D-Asn were significantly associated with the progression of CKD in mutually-adjusted Cox regression analyses; the risk of composite end point (developing to ESKD or death before ESKD) was elevated from 2.7- to 3.8-fold in those with higher levels of plasma D-Ser and D-Asn. These findings identified chiral amino acids as potential biomarkers in kidney diseases. PMID- 27188855 TI - Measurement of 1,5-anhydroglucitol in blood and saliva: from non-targeted metabolomics to biochemical assay. AB - BACKGROUND: Diabetes testing using saliva, rather than blood and urine, could facilitate diabetes screening in public spaces. We previously identified 1,5 anhydro-D-glucitol (1,5-AG) in saliva as a diabetes biomarker. The GlycomarkTM assay kit is FDA approved for 1,5-AG measurement in blood. Here we evaluated its applicability for 1,5-AG quantification in saliva. METHODS: Using pooled saliva samples, we validated GlycomarkTM assay use with a RX Daytona(+) clinical chemistry analyser. We then used this set-up to analyse 82 paired blood and saliva samples from a diabetes case-control study, for which broad mass spectrometry-based characterization of the blood and saliva metabolome was also available. Osmolality was measured to account for potential variability in saliva samples. RESULTS: The technical variability of the read-outs for the pooled saliva samples (CV = 2.05 %) was comparable to that obtained with manufacturer provided blood surrogate quality controls (CV = 1.38-1.8 %). We found a high correlation between Glycomark assay and mass spectrometry measurements of serum 1,5-AG (r(2) = 0.902), showing reproducibility of the non-targeted metabolomics results. The significant correlation between the osmolality measurements performed at two independent platforms with the time interval of 2 years (r(2) = 0.887), also indicates the sample integrity. The assay read-out for saliva was not correlated with the mass spectrometry-based 1,5-AG saliva measurements. Comparison with the full saliva metabolome revealed a high correlation of the saliva assay read-outs with galactose. CONCLUSIONS: GlycomarkTM assay read-outs for saliva were stable and replicable. However, the signal was dominated by galactose, which is biochemically similar to 1,5-AG and absent in blood. Adapting the 1,5-AG kit for saliva analysis will require enzymatic depletion of galactose. This should be feasible, since the assay already includes a similar step for glucose depletion from blood samples. PMID- 27188856 TI - Rothia aerolata sp. nov., isolated from exhaust air of a pig barn. AB - A Gram-stain-positive, coccoid, oxidase-negative, non-motile isolate from exhaust air of a pig barn, collected on 17 September 2014 and designated strain 140917 MRSA-09T, was subjected to a comprehensive taxonomic investigation. A comparative analysis of the 16S rRNA gene sequence showed highest similarities to Rothia amarae, Rothia terrae and Rothia endophytica (all <97.8 %). The G+C content of the genomic DNA was 58.9 mol %. The quinone system consisted of the major menaquinones MK-8 and MK-7. The polar lipid profile of strain 140917-MRSA-09T contained the major lipids diphosphatidylglycerol and phosphatidylglycerol and moderate amounts of dimannosylglyceride and trimannosyldiacylglycerol. The polyamine pattern was composed of the major amines putrescine and spermidine. In the fatty acid profile, iso- and anteiso-branched acids predominated (anteiso-C15 : 0, anteiso-C17 : 0, iso-C16 : 0). The strain showed a chemoheterotrophic metabolism and was able to grow aerobically well on nutrient-rich media at temperatures from 15-36 degrees C (weak at 42 degrees C), pH 5.5-9.5 and NaCl concentrations ranging from 0 to 7 % (w/v). Growth under anaerobic conditions was weak. Physiological traits as well as unique traits in the quinone pattern and the fatty acid pattern distinguished strain 140917-MRSA-09T from the most closely related species. All these data showed that strain 140917-MRSA-09T is a representative of a novel species of the genus Rothia, for which we propose the name Rothia aerolata sp. nov. The type strain is 140917-MRSA-09T (=LMG 29446T=CCM 8669T). PMID- 27188854 TI - Pre-clinical evaluation of CYP 2D6 dependent drug-drug interactions between primaquine and SSRI/SNRI antidepressants. AB - BACKGROUND: The liver-stage anti-malarial activity of primaquine and other 8 aminoquinoline molecules has been linked to bio-activation through CYP 2D6 metabolism. Factors such as CYP 2D6 poor metabolizer status and/or co administration of drugs that inhibit/interact with CYP 2D6 could alter the pharmacological properties of primaquine. METHODS: In the present study, the inhibitory potential of the selective serotonin reuptake inhibitor (SSRI) and serotonin norepinephrine reuptake inhibitor (SNRI) classes of antidepressants for CYP 2D6-mediated primaquine metabolism was assessed using in vitro drug metabolism and in vivo pharmacological assays. RESULTS: The SSRI/SNRI classes of drug displayed a range of inhibitory activities on CYP 2D6-mediated metabolism of primaquine in vitro (IC50 1-94 MUM). Fluoxetine and paroxetine were the most potent inhibitors (IC50 ~1 uM) of CYP 2D6-mediated primaquine metabolism, while desvenlafaxine was the least potent (IC50 ~94 uM). The most potent CYP 2D6 inhibitor, fluoxetine, was chosen to investigate the potential pharmacological consequences of co-administration with primaquine in vivo. The pharmacokinetics of a CYP 2D6-dependent primaquine metabolite were altered upon co-administration with fluoxetine. Additionally, in a mouse malaria model, co-administration of fluoxetine with primaquine reduced primaquine anti-malarial efficacy. CONCLUSIONS: These results are the first from controlled pre-clinical experiments that indicate that primaquine pharmacological properties can be modulated upon co incubation/administration with drugs that are known to interact with CYP 2D6. These results highlight the potential for CYP 2D6-mediated drug-drug interactions with primaquine and indicate that the SSRI/SNRI antidepressants could be used as probe molecules to address the primaquine-CYP 2D6 DDI link in clinical studies. Additionally, CYP 2D6-mediated drug-drug interactions can be considered when examining the possible causes of human primaquine therapy failures. PMID- 27188857 TI - Inflammatory cytokine levels, disease activity, and function of patients with rheumatoid arthritis treated with combined conventional disease-modifying antirheumatic drugs or biologics. AB - The objective of this study was to compare the effects of treatment by combined conventional disease-modifying antirheumatic drugs (cDMARDs) or biologics on cytokines, disease activity, and function in rheumatoid arthritis (RA). Sera from a cohort of 81 patients with long-standing RA treated with combined cDMARDs or biologics were measured for 12 cytokines. Comparisons of serum cytokine concentrations with treatment types (combination 2, 3 cDMARDs or biologics), serologic status (positivity for RF and anti-cyclic citrullinated peptide antibody (anti-CCP Ab)), DAS28-ESR, and function were performed. Spearman correlation coefficients between individual cytokines and clinical parameters were explored. Approximately half of the patients were prescribed two cDMARDs. Mean duration of current treatment was 42 months. More than 70 % had moderate disease activity or normal function/slight disability. Serum concentrations of interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-23, IL-33, interferon (IFN)-gamma, granulocyte monocyte-colony stimulating factor (GM-CSF), and TNF-alpha in patients taking combined cDMARDs did not significantly differ from those on biologics. Seventy-nine serum samples (97.5 %) had undetectable levels of 1 to 10 cytokines. Concentrations of several cytokines were significantly higher in patients with moderate to high disease activity, seropositive or poor functional status. Weak correlations between cytokine levels and RA disease activity or function were demonstrated. The highest correlation coefficients were observed with IL-33, IL-8, and IL-6. Long-term treatment with cDMARDs did not differ from biologics with respect to cytokine concentrations, disease activity, and function. The cytokine profiles in established RA were mainly those produced from effector cells, especially IL-6, IL-8, and IL-33. Both IL-8 and IL-33 may be potential biomarkers and/or treatment targets in patients with late RA. PMID- 27188859 TI - Politics, culture, and the legitimacy of disease: the case of Buerger's disease. AB - Thromboangiitis obliterans (TAO) or Buerger's disease is a rare form of vasculitis with distinctive clinical and pathological features that carries significant morbidity, often leading to amputation, and is strongly associated with tobacco smoking. Despite its distinctive clinicopathological characteristics, the existence of TAO as an entity sui generis was challenged for many years as it languished in relative obscurity. Then, as societal attitudes towards smoking changed, TAO not only became accepted as a disease entity, it quite literally became a poster child to illustrate the ills of smoking. Herein, we examine the history of TAO to illustrate the power of societal attitudes and politics in shaping medicine. PMID- 27188858 TI - Association of IL1Beta (-511 A/C) and IL6 (-174 G > C) polymorphisms with higher disease activity and clinical pattern of psoriatic arthritis. AB - The objective of this study is to analyze whether IL1beta (-511G > A) and IL6 ( 174 G > C) polymorphisms are associated with inflammatory activity, radiographic damage or clinical pattern of psoriatic arthritis (PsA). One hundred twenty-five patients classified as PsA according to the Classification of Psoriatic Arthritis (CASPAR) criteria were included. Patients were stratified according to their clinical pattern at inclusion as peripheral, axial, or mixed involvement. Disease activity in peripheral or mixed forms was measured using the number of swollen and tender joints, pain analog visual scale, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and disease activity score 28 (DAS28). Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was used for axial and mixed forms, as were pain visual analog scale, ESR and CRP. Radiographic damage was evaluated using a modified Sharp score and modified stoke ankylosing spondylitis spinal score (SASSSm). The polymorphisms for the promoter region of IL1beta (-511 G/A) and IL-6 (-174 G/C) were analyzed. The G allele of IL1B ( 511G/A) polymorphism was associated with higher peripheral joint disease activity (OR 3.13; p < 0.0004; CI 95 % 1.43-6.82, p (corrected) <0.008), while the G allele of the IL6 (174G > C) polymorphism presented a strong trend to be associated with peripheral forms (70.86 %) (OR 1.89; p < 0.03; CI 95 % 1.06-3.39, p-corrected 0.05). In addition, this allele showed a lower association with HLA B27 (15.78 %) compared with C allele (28.57 %) (OR 0.469; p = 0.02; CI 95 % 0.238 0.923, p-corrected 0.03). This study suggests that the G allele polymorphism of IL1B (-511 A/C) is associated with higher peripheral joint disease activity. On the other hand, the IL6 (-174 G/C) polymorphism showed a strong trend to be associated with the peripheral pattern of PsA. PMID- 27188861 TI - Editorial. AB - To optimize treatment, we need to understand biology of different diseases in much more detail with emphasis on morphological, proteomic, genetic and epigenetic grounds. Keeping in view the facts and stimulating developments in molecular pathology, it is worthwhile to present an up-date on this topic.It is becoming progressively more understandable that exciting fields of pharmacogenomics and pharmacogenetics have revolutionized field of medicine. Better understanding of underlying mechanisms of different diseases has provided us with better ways to treat illnesses. There cannot be a distinct definition of 'discipline' of pathology, mainly because investigation of human disease encompasses all the scientific disciplines of biomedical research. Sen et al reported that hyperbaric oxygen (HBO) administration affected the endocrinological functions of fat tissue. Observation of significant increases in leptin, visfatin and IL-10 levels, leads to the consideration that in near future HBO administration may be applied as treatment for obesity, DM, eating disorders and obesity related diseases... PMID- 27188860 TI - Effect of prenatal selective serotonin reuptake inhibitor (SSRI) exposure on birthweight and gestational age: a sibling-controlled cohort study. AB - Background: Up to 10% of women are exposed to selective serotonin reuptake inhibitors (SSRIs) during pregnancy. Information on their effect on birthweight and gestational age remains conflicting. The aim of this sibling-controlled prospective cohort study is to address shared geneticand family-level confounding to investigate the effects of prenatal SSRI exposure and maternal depression on birthweight and gestational age. Methods: We used the Norwegian Mother and Child Cohort Study (MoBa) and the Medical Birth Registry of Norway (MBRN). Our study population consisted of 27 756 siblings; 194 were prenatally exposed to SSRIs and 27 500 were unexposed to any antidepressant medication. Random and fixed effects analysis with propensity score adjustment was used to evaluate the effectson birthweight and gestational age. Results: SSRI exposure during two or more trimesters was associated with a decrease in birthweight of 205 g [95% confidence interval (CI) -372 to - 38] and a decrease in gestational length of 4.9 days (95% CI - 9.1 to - 1.4). Neither maternal SSRI use in one trimester, lifetime history of major depression nor depressive symptoms during pregnancy were associated with these pregnancy outcomes (for non-pharmacologically treated depression in two periods in pregnancy, +5 g (95% CI - 56 to + 67) and +4.9 days (95% CI - 4.7 to + 14.7), respectively). Conclusions: Prenatal exposure to SSRIs during two or more trimesters may decrease birthweight and gestational length. Our results indicate that neither maternal depression nor shared genetics and family environment fully explain this association. PMID- 27188862 TI - The effect of glycyrrhizic acid on traumatic spinal cord injury in rats. AB - Spine injury associated with traumatic spinal cord injury eventuates in oxidative stress, inflammation and neuronal apoptosis. The aim of this study is to find out whether the glycyrrhizic acid treatment protects spinal cord from traumatic injuries in rats. To this end, the rats were divided into three groups: group I; control group (no drug or operation, n=8), group II; traumatic spinal cord injury group (TSCI, n=8) and group III; glycyrrhizic acid group (TSCI-GA, 80 mg/kg, n=8). Total laminectomy was performed at T10 level. A balloon angioplasty catheter was inserted into the T9 level thoracic spinal cord extradurally. The rats were evaluated with the Tarlov Scale. After 24 hours, spinal cord tissues were taken for biochemical and histopathological examinations. TSCI effectuates unwanted results on tissues, antioxidant systems and cell membranes. Antioxidant enzyme level decreased and lipid peroxidation increased. However, TSCI led to inflammation and apoptosis. Glycyrrhizic acid treatment provided a significant decrease in lipid peroxidation in group III in comparison with group II. Moreover, nuclear respiratory factor 1 levels and superoxide dismutase activity of group III were significantly higher than group II (p<0.05). The histopathological and immunohistochemical results revealed that the numbers of apoptotic and necrotic neuron, edema, hemorrhage, inflammatory cells, NF-kappaB and S100B expressions were significantly lower than group II (p<0.05). Our study showed that the glycyrrhizic acid treatment reduced oxidative stress and inflammation, and promoted the neuronal functions in traumatic spinal cord injury. PMID- 27188863 TI - The effects of Advanced Glycation End Products (RAGE)-374T/A and Gly82Ser variants and soluble-RAGE levels to obesity in children. AB - In recent years, studies related to advanced glycation end products (AGE) and their interaction with their receptors (RAGE) have advanced our knowledge of the roles of these molecules in different diseases. However, studies concerning AGE RAGE interaction in obesity are limited and the results are conflicting. RAGE gene is located on 6p21.3, has several polymorphic sites including -374T/A, a functional polymorphism in the promoter region, and Gly82Ser, present within the ligand-binding domain. In the present study, the determination of possible risks in the development of obesity according to RAGE polymorhisms and plasma levels of RAGE (sRAGE) was aimed. 87 obese and 78 healthy children were included in this study. Genomic DNA was isolated with salting-out procedure. RAGE polymorphisms were analyzed by PCR based techniques. In contrast to Gly82Ser, -374T/A allelic and genotypic frequencies were not different between study groups. Ser(SerSer+GlySer genotype) allele frequency was higher in obese cases than controls (74.20%->25.80%,OR:2.573,95%CI:1.789-3.699;p<0.01). In obese cases, blood glycose (92.50+/-2.80->87.00+/-1.16; p=0.025) and HDL-C (46.14+/-2.75 >39.84+/-1.82;p=0.057) levels were higher than TT genotype carriers. As for Gly82Ser polymorphism, HDL-C (p=0.004) and FT4 (p=0.020) levels were different in obese cases, the order was SerSer>GlySer>GlyGly for HDL-C, and opposite for FT4. Besides, Ser carriers had lower insulin (p=0.038) and homa-IR (p=0.081) levels than GG genotype. sRAGE levels were different between obese and control seperately or in combination with RAGE polymorphisms (p<0.05), the order of sRAGE was TT>TA>AA for -374T/A and SerSer>GlyGly>GlySer for Gly82Ser. According to our results SerSer genotype could have significant effects on sRAGE levels, and increased sRAGE levels and Gly82Ser polymorphism either combinatorially or seperately increased the propensity towards obesity. PMID- 27188864 TI - Investigation of endocrine and immunological response in fat tissue to hyperbaric oxygen administration in rats. AB - Though HBO treatment is becoming more common, the mechanism of action is not fully known. The positive effects of HBO administration on the inflammatory response is thought to be a possible basic mechanism. As a result, we aimed to research whether endocrine and immunological response of fat tissue changes in rats given HBO treatment model. This research was carried out on Wistar albino rats, they were treated with hyperbaric oxygen therapy. Their fatty tissue were taken from the abdomen, gene expression of the cytokines and adipokines were analyzed with Real time PCR method. When the gene expression of hormones and cytokines by fat tissue was examined, the leptin, visfatin, TNF-alpha, IL-1beta and IL-10 levels in the HBO treatment group were statistically significantly increased compared to the control group (p=0.0313, p=0.0156, p=0.0156, p=0.0156, p=0.0313). In conclusion, in our study we identified that HBO administration affected the endochrinological functions of fat tissue. PMID- 27188865 TI - Relationship between betatrophin levels and metabolic parameters in patients with polycystic ovary syndrome. AB - To evaluate the status of serum betatrophin levels and potential relations between metabolic parameters and betatrophin levels in patients with polycystic ovary syndrome. We included patients newly diagnosed with PCOS in our study. Fifty-seven female patients (30 patients with PCOS and 27 healthy control subjects) were enrolled in this study. Serum betatrophin levels were measured using a betatrophin enzyme-linked immunosorbent assay kit. Insulin resistance was calculated using the homeostasis model of the assessment-insulin resistance index formula. The betatrophin level was 1538,85 ng/L in the patient group and 2440,46 ng/L in the control group, and the difference was statistically significant (p=0.003). A significantly negative correlation was found between betatrophin level and insulin, HOMA-IR, and BMI. Betatrophin levels in patients with PCOS are lower than those without PCOS and inversely related to insulin resistance. PMID- 27188867 TI - Hypoxia and laser enhance expression of SDF-1 in muscles cells. AB - Targeted homing of transplanted mesenchymal stem cells (MSCs) is a decades old discussion in regenerative medicine. It has been proved that stromal cell-derived factor-1 (SDF-1alpha) is a potent chemoattractant of MSCs. Therefore, different strategies have been used to increase secretion of SDF-1alpha in damaged tissues to elevate targeted homing of MSCs. Previous studies have revealed that increased SDF-1alpha expression in hypoxic necrotic tissues and also low-level laser exposure enhanced angiogenesis in injured tissues. Herein, human skeletal and cardiac muscle cells (HSKM and HCM) were treated with hypoxia and low level laser to see their effects on expression of SDF-1alpha and on MSCs migration towards these treated cells. The optimal treatment conditions were determined by investigating the cellular viability after treatment. Real-Time PCR and Western blot analysis were done to study the expression of SDF-1alpha in treated cells. Migration potential of MSCs toward hypoxic and laser treated cells was investigated via migration assay. MTT assay revealed that laser and hypoxia treatment had no effect on the viability of HCM, HSKM compared with Glioblastoma cells. Real-Time PCR showed 16- and 90-fold elevation in mRNA of SDF-1alpha in HSKM and HCM cells, respectively, in laser treated with 12 J/cm2 intensity. In these two groups, selected as optimal conditions, HIF-1alpha expression showed maximum fold changes that might be partly because of response to treatments help to SDF-1alpha expression. It can be concluded that hypoxia and laser treatments may recruit MSCs and applied as a useful strategy for the further targeted stem cell homing. PMID- 27188866 TI - Are there possible associations between MnSOD and GPx1 gene variants for laryngeal cancer risk or disease progression? AB - Laryngeal squamous cell carcinoma (LSCC) is a multifaceted and genomically complex disease and cellular and preclinical studies have demystified wide ranging molecular mechanisms which underpin its development and progression and resistance against wide ranging molecular therapeutics. Oxidative stress is a widely studied molecular mechanism and reportedly involved in carcinogenesis. Increasingly it is being realized that accumulation of Reactive Oxygen Species (ROS) activates defensive mechanism to counteract oxidative stress induced damage. Manganese superoxide dismutase (MnSOD) and glutathione peroxidase (GPx) are important members of defensive machinery. We investigated whether the polymorphisms of MnSOD (Ala-9Val, rs4880) and GPx1 (Pro198Leu, rs1050450) are associated with LSCC and also evaluated possible interactions between these polymorphisms and various lifestyle factors or pathological features of patients. For this purpose, 67 LSCC patients and 73 healty controls were enrolled. Molecular assessment of MnSOD and GPx1 variants were determined with polymerase chain reaction-restriction fragment length polymorphism techniques. We found that the frequency of both heterozygous PL genotype and P allele was considerably higher in patients with advanced tumor stage (T3/T4) than in those with early tumor stage (T1/T2) (OR= 5.106; 95% CI=1.372-19.004; p<0.001, OR=5.787; 95% CI =1.564-21.414; p<0.001 respectively). Although the frequency of ValVal/LL combine genotype was significantly decreased (OR=0.204, 95% CI=0.055-0.760; p=0.021), the frequency of ValAla/PL combine genotypes was higher in patients with stage T3/T4 than in those patients with stage T1/T2 (p=0.027). Consequently, we have concluded that variants of GPx1 and MnSOD should not be considered as a risk factor of LSCC, only may be accepted as a prognostic markers. Use of new technologies such as metabolomics and deep DNA sequencing will prove to be helpful in developing a deeper knowledge related to how cancer cell metabolism adapts and provides a buffer against increased oxidative stress. PMID- 27188868 TI - Tudor tells about new twists in the story tale of SMURFs. AB - Smad ubiquitin regulatory factors (SMURFS) belong to the HECT- family of E3 ubiquitin ligases. This family has two members, SMURF1 and SMURF2. SMURFs have emerged as well studied negative regulators of TGF induced intracellular signaling. However, increasingly it is being realized that SMURFs tactfully modulate an array of proteins in different cancers. This review sets spotlight on how SMURF1 and SMURF2 communicate with effectors of different signaling pathways during the multistep progression to cancer. We also summarize how microRNAs (miRNAs) effectively control SMURFs in different cancers. Role of SMURFs is context dependent in different cancers and better concepts related to miRNA regulation of SMURFs in different stages and steps of cancer will be helpful in efficient translation of laboratory findings to clinic. PMID- 27188870 TI - Ganoderma lucidum total triterpenes attenuate DLA induced ascites and EAC induced solid tumours in Swiss albino mice. AB - G. lucidum total triterpenes were assessed for its apoptosis-inducing and anti tumour activities. The ability of the total triterpenes to induce apoptosis was evaluated in Dalton's lymphoma ascites (DLA) and Ehrlich's ascites carcinoma (EAC) cell lines. Total triterpenes were found to be highly cytotoxic to DLA and EAC cell lines with IC50 values 5 +/- 0.32 and 7.9 +/- 0.2 ug/ml respectively. Total triterpenes induced apoptosis in both cell lines which is evident from the DNA fragmentation assay. Anti-tumour activity was accessed using DLA induced solid and EAC induced ascites tumour models in Swiss albino mice. Administration of 10, 50 and 100 mg/kg b. wt. total triterpenes showed 11.86, 27.27 and 40.57% increase in life span of animals in ascites tumour model. Treatment with 10, 50 and 100 mg/kg b. wt. total triterpenes exhibited 76.86, 85.01 and 91.03% inhibition in tumour volume and 67.96, 72.38 and 77.90% inhibition in tumour weight respectively in the solid tumour model. The study reveals the significant dose-dependent anti-tumour activity of total triterpenes in both models. Total triterpenes were more active against the solid tumour than the ascites tumour. The anti-oxidant potential and ability to induce cell-specific apoptosis could be contributing to its anti-tumour activities. PMID- 27188869 TI - Adipose derived mesenchymal stem cells express keratinocyte lineage markers in a co-culture model. AB - Cutaneous wound healing is a complex type of biological event involving proliferation, differentiation, reprograming, trans/de-differentiation, recruitment, migration, and apoptosis of a number of cells (keratinocytes, fibroblasts, endothelial cells, nerve cells and stem cells) to regenerate a multi layered tissue that is damaged by either internal or external factors. The exact regeneration mechanism of damaged skin is still unknown but the epithelial and other kinds of stem cells located in skin play crucial roles in the healing process. In this work, a co-culture model composed of adipose derived mesenchymal stem cells and keratinocytes was developed to understand the cellular differentiation behaviour in wound healing. Human mesenchymal stem cells were isolated from waste lipoaspirates. Keratinocytes were isolated from neonatal rats skin as well from human adult skin. Both types of cells were cultured and their culturing behaviour was observed microscopically under regular intervals of time. The identity of both cells was confirmed by flow cytometry and qRT-PCR. Cells were co-cultured under the proposed co-culturing model and the model was observed for 7, 14 and 21 days. The cellular behaviour was studied based on change in morphology, colonization, stratification, migration and expression of molecular markers. Expression of molecular markers was studied at transcriptional level and change in cellular morphology and migration capabilities was observed under the invert microscope regularly. Successfully isolated and characterized mesenchymal stem cells were found to express keratinocyte lineage markers i.e. K5, K10, K14, K18, K19 and Involucrin when co-cultured with keratinocytes after 14 and 21 days. Their expression was found to increase by increasing the time span of cell culturing. The keratinocyte colonies started to disappear after 10 days of culturing which might be due to stratification process initiated by possibly transdifferentiated stem cells. It can be concluded that mesenchymal stem cells can regenerate the damaged skin if transplanted to damaged area but for their successful differentiation and enhanced regeneration, they need a population of keratinocytes in situ which need further experiments for validation of co-culture model and its potential for being used in clinics. PMID- 27188872 TI - How similar are biosimilars? PMID- 27188871 TI - Anticancer activity of Cynodon dactylon and Oxalis corniculata on Hep2 cell line. AB - Bioactive chemicals isolated from plants have attracted considerable attention over the years and overwhelmingly increasing laboratory findings are emphasizing on tumor suppressing properties of these natural agents in genetically and chemically induced animal carcinogenesis models. We studied in vitro anticancer activity of organic extracts of Cynodon dactylon and Oxalis corniculata on Hep2 cell line and it was compared with normal human corneal epithelial cells (HCEC) by using MTT assay. Real Time PCR was conducted for p53 and PTEN genes in treated cancer cell line. DNA fragmentation assay was also carried out to note DNA damaging effects of the extracts. The minimally effective concentration of ethanolic extract of Cynodon dactylon and methanolic extract of Oxalis corniculata that was nontoxic to HCEC but toxic to Hep2 was recorded (IC50) at a concentration of 0.042mg/ml (49.48 % cell death) and 0.048mg/ml (47.93% cell death) respectively, which was comparable to the positive control. Our results indicated dose dependent increase in cell death. P53 and PTEN did not show significant increase in treated cell line. Moreover, DNA damaging effects were also not detected in treated cancer cell line. Anticancer activity of these plants on the cancer cell line showed the presence of anticancer components which should be characterized to be used as anticancer therapy. PMID- 27188873 TI - Triazole resistance mediated by mutations of a conserved active site tyrosine in fungal lanosterol 14alpha-demethylase. AB - Emergence of fungal strains showing resistance to triazole drugs can make treatment of fungal disease problematic. Triazole resistance can arise due to single mutations in the drug target lanosterol 14alpha-demethylase (Erg11p/CYP51). We have determined how commonly occurring single site mutations in pathogenic fungi affect triazole binding using Saccharomyces cerevisiae Erg11p (ScErg11p) as a target surrogate. The mutations Y140F/H were introduced into full length hexahistidine-tagged ScErg11p. Phenotypes and high-resolution X-ray crystal structures were determined for the mutant enzymes complexed with short tailed (fluconazole and voriconazole) or long-tailed (itraconazole and posaconazole) triazoles and wild type enzyme complexed with voriconazole. The mutations disrupted a water-mediated hydrogen bond network involved in binding of short-tailed triazoles, which contain a tertiary hydroxyl not present in long tailed triazoles. This appears to be the mechanism by which resistance to these short chain azoles occurs. Understanding how these mutations affect drug affinity will aid the design of azoles that overcome resistance. PMID- 27188875 TI - Palliative lumboperitoneal shunt for leptomeningeal metastasis-related hydrocephalus: A case series. AB - BACKGROUND: Leptomeningeal metastasis-related hydrocephalus causes distress to patients with end-stage cancer through headache and other symptoms by elevating intracranial pressure, thus reducing quality of life. Ventriculoperitoneal shunt has been used as a treatment option in palliative care. We review four cases of patients who underwent lumboperitoneal shunt for leptomeningeal metastasis related hydrocephalus. CASES: All patients suffered from severe headache and nausea. The primary lesion was histologically diagnosed as lung adenocarcinoma in each case. The duration from diagnosis to onset of hydrocephalus symptoms ranged from 0 to 52 (mean 26) months. Cerebrospinal fluid pressure in every case was above the normal range due to high intracranial pressure. Case management: Conventional procedures for lumboperitoneal shunt were employed for all patients. Adjustable pressure valves were retrofitted into the shunt system. Case outcome: Three patients demonstrated significant improvement of clinical symptoms and quality of life after placement of lumboperitoneal shunts. In two cases, not only did performance status improve to independent daily activity but also comparatively long-term survival was achieved due to subsequent chemotherapies after surgery. No symptoms of peritoneal dissemination by floating cancer cells in cerebrospinal fluid were seen in any patients. CONCLUSION: Lumboperitoneal shunt appears to improve quality of life if the patient is suffering from symptoms of leptomeningeal metastasis-related hydrocephalus. Compared to ventriculoperitoneal shunt, lumboperitoneal shunt is less invasive and simpler, providing a suitable option for frail patients with end-stage cancer. Adjustable pressure shunt valves can cope with varying symptoms and ventricle sizes. PMID- 27188874 TI - Novel skin chamber for rat ischemic flap studies in regenerative wound repair. AB - BACKGROUND: In plastic surgery, skin flap is an important approach to reconstructive wound repairs. The rat dorsal skin flap is a clinically relevant and popular animal model to investigate and evaluate flap survival and necrosis. Nonetheless, flap survival is often unstable with unpredictable outcomes, regardless of previous attempts at design modification. METHODS & RESULTS: In the present study, we report a novel flap chamber that provides stable and reproducible outcomes by separating the dorsal skin flap from its surrounding skin by in situ immobilization. The flap chamber blocks circulation that disturbs flap ischemia from both basal and lateral sides of the flap tissue. Demarcation of skin necrosis is macroscopically evident on the flap and supported by distinct changes in histological architecture under microscopic examination. The utility of the novel skin flap chamber is further proven by applying it to the examination of flap survival in streptozotocin-induced diabetic rats with an increase in skin necrosis. The flap chamber also affords size modifications where a narrower flap chamber increases ischemia and provides manipulable therapeutic windows for studying cell therapies. Accordingly, intradermal injection of endothelial cells 3 days before flap ischemia significantly increases the survival of skin flaps. CONCLUSIONS: The novel flap chamber not only may stabilize the skin flap and provide reproducible outcomes that overcome the shortfalls of the traditional ischemic flap but also may afford size modifications that support research designs and test therapeutic approaches to regenerative repair. PMID- 27188876 TI - In and out of love with hip-hop: saliency of sexual scripts for young adult African American women in hip-hop and Black-oriented television. AB - Hip-hop media and Black-oriented reality television are powerful mechanisms for conveying and promoting stereotypes of Black women. Black women's sexuality is frequently presented as highly-salient in each medium. However, little is known about the impact of those images on Black women's sexuality and identity. The current study uses focus-group methodology to engage young adult Black in critical discussion of two predominant sexual scripts found in hip-hop music and Black-oriented reality television - the Freak and the Gold Digger. Analyses revealed shared and distinct aspects of each sexual script represented in both media and the impact of those scripts on participants' experiences. Implications for future research are discussed. PMID- 27188877 TI - Preoperative pain catastrophizing and postoperative pain after total knee arthroplasty: a prospective cohort study with one year follow-up. AB - BACKGROUND: Pain relief is likely to be the most important long-term outcome for patients undergoing total knee arthroplasty (TKA). However, research indicates that persistent pain (> 3 months) is a considerable problem, affecting up to 34 % of patients. Pain catastrophizing might contribute to acute and persistent pain experienced after surgery. The primary aim of the present study was to examine the association between preoperative pain catastrophizing and postoperative pain in patients undergoing TKA up to one year after surgery. Second, we wanted to investigate a possible shift in postoperative catastrophizing. METHODS: In this prospective cohort study, 71 TKA patients were included consecutively between January and June 2013. Pain was assessed with the Brief Pain Inventory (BPI) and the item "average pain" was used as the main outcome. Pain catastrophizing was measured by the Pain Catastrophizing Scale (PCS). Questionnaires were completed prior to surgery (baseline) and at two days, two weeks, eight weeks and one year postoperatively. RESULTS: Mean (SD) preoperative pain score was 5.4 (2.2), reduced to 2.9 (2.3) after eight weeks and 2.4 (2.4) after one year (p < 0.001). The overall median preoperative PCS score was 17.0 (7.8-28.3). The overall model estimated PCS mean score was 7.6 at eight weeks and 6.5 at one year follow-up. The results at eight weeks and one year follow-up were both significantly lower than the preoperative value (p < 0.001). The preoperative PCS score was not associated with the postoperative pain score (p = 0.942), while preoperative pain was a significant covariate in the mixed linear model (p < 0.001). CONCLUSIONS: No associations were found between preoperative pain catastrophizing and pain eight weeks or one year after surgery. The decrease in PCS-scores challenges evidence regarding the stability of pain catastrophizing. However, larger studies of psychological risk factors for pain after TKA are warranted. PMID- 27188878 TI - Prolonged dry apnoea: effects on brain activity and physiological functions in breath-hold divers and non-divers. AB - PURPOSE: The aim of the study was to investigate the effects of voluntary breath holding on brain activity and physiological functions. We hypothesised that prolonged apnoea would trigger cerebral hypoxia, resulting in a decrease of brain performance; and the apnoea's effects would be more pronounced in breath-hold divers. METHODS: Trained breath-hold divers and non-divers performed maximal dry breath-holdings. Lung volume, alveolar partial pressures of O2 and CO2, attention and anxiety levels were estimated. Heart rate, blood pressure, arterial blood oxygenation, brain tissue oxygenation, EEG, and DC potential were monitored continuously during breath-holding. RESULTS: There were a few significant changes in electrical brain activity caused by prolonged apnoea. Brain tissue oxygenation index and DC potential were relatively stable up to the end of the apnoea in breath-hold divers and non-divers. We also did not observe any decrease of attention level or speed of processing immediately after breath-holding. Interestingly, trained breath-hold divers had some peculiarities in EEG activity at resting state (before any breath-holding): non-spindled, sharpened alpha rhythm; slowed-down alpha with the frequency nearer to the theta band; and untypical spatial pattern of alpha activity. CONCLUSION: Our findings contradicted the primary hypothesis. Apnoea up to 5 min does not lead to notable cerebral hypoxia or a decrease of brain performance in either breath-hold divers or non-divers. It seems to be the result of the compensatory mechanisms similar to the diving response aimed at centralising blood circulation and reducing peripheral O2 uptake. Adaptive changes during apnoea are much more prominent in trained breath-hold divers. PMID- 27188880 TI - Single-Dose Fluconazole Therapy for Oral Thrush in Hospice and Palliative Medicine Patients. AB - BACKGROUND: Oral thrush is a common fungal infection of the mouth experienced by palliative medicine and hospice patients who have advanced cancer. Individuals often experience distressing symptoms that affect their oral intake with most regimens adding to pill burden. This is an open-label prospective observational study to assess the efficacy of a single-dose fluconazole 150 mg for oral thrush. METHODS: Palliative medicine and hospice patients with a clinical diagnosis of oral thrush, a life expectancy of more than 1 week, and were able to swallow were enrolled. Signs and symptoms were evaluated on day 1 prior to administration of 150 mg of fluconazole and between days 3 to 5 after treatment. RESULTS: Of 57 patients, 55 (96.5%) had more than 50% improvement in signs and symptoms. Both the number and severity of symptoms changed significantly posttreatment ( P < .001). Side effects were few. CONCLUSION: Single-dose fluconazole 150 mg is an effective treatment of oral thrush for individuals with advanced cancer. PMID- 27188879 TI - Historical Incidence of Spontaneous Lesions in Kidneys from Naive Swine Utilized In Interventional Renal Denervation Studies. AB - The use of preclinical animal models is integral to the safety assessment, pathogenesis research, and testing of diagnostic technologies and therapeutic interventions. With inherent similarity to human anatomy and physiology, various porcine models have been the preferred preclinical model in some research areas such as medical devices, wound healing, and skin therapies. The porcine model has been the cornerstone for interventional cardiology for the evaluation and development of this catheter-based renal denervation (RDN) therapy. The porcine model provides similar vascular access and renal neurovascular anatomy to humans. In these preclinical studies, the downstream kidneys from treated arteries are assessed for possible histopathological changes in the vessel dependent territories. In assessing renal safety following RDN, it becomes critical to distinguish treatment-related changes from pre-existing background pathologies. The incidence of background pathological changes in porcine kidneys has not been previously established in normal clinically healthy. Samples from the cranial, middle, and caudal portion of 331 naive kidneys from 181 swine were processed histologically to slides and evaluated microscopically. The most commonly encountered spontaneous changes were chronic pyelonephritis found in nearly half of the evaluated naive kidneys (~40 %; score 1 = 91 %, score 2 = 8.4 %, score 3 = 0.76 %) followed by chronic interstitial inflammation in 9.7 % of the kidneys (score 1 = 90.6 %, score 2 = 9.4 %). Interestingly, there were a few rare spontaneous vascular changes that could potentially affect data interpretation in interventional and toxicology studies: arteritis and arteriolar dissection. The presence of pelvic cysts was a common occurrence (6.3 %) in the kidney. The domestic swine is a widely used preclinical species in interventional research, namely in the emerging field of transcatheter renal denervation. This retrospective study presents the historical incidence of spontaneous lesions recorded in the kidneys from naive pigs enrolled in renal denervation studies. There were commonly encountered changes of little pathological consequence such as pyelonephritis or pelvic cysts and rare vascular changes such as arteritis and arteriolar dissection that were of greater potential impact on study data interpretation. These results offer a benchmark by which to gage the potential effect of a procedure or treatment on renal histopathology in swine and assist in data interpretation. PMID- 27188881 TI - The cardiopulmonary effects and quality of anesthesia after induction with alfaxalone in 2-hydroxypropyl-beta-cyclodextrin in dogs and cats: a systematic review. AB - To systematically review the quality of evidence comparing the cardiopulmonary effects and quality of anesthesia after induction with alfaxalone vs. other anesthetic agents in dogs and cats. Studies published from 2001 until 20th May 2013 were identified with the terms 'alfaxan' OR 'alfaxalone' OR 'alphaxalone' in electronic databases: Discovery, PubMed, ScienceDirect, and Wiley Interscience. The study design and risk of bias of all included studies were assessed. Twenty two studies from 408 (22 of 408, 5.39%) satisfied the inclusion criteria. Fourteen studies (14 of 22, 64%) focused on dogs and nine (9 of 22, 40%) on cats. One study had both dogs and cats as subjects. (Hunt et al., 2013) Twelve studies were rated an LOE1, and six of these as ROB1. One, seven, and two studies were rated as LOE2, LOE3, and LOE5, respectively. In dogs, strong evidence shows that induction quality with either alfaxalone-HPCD or propofol is smooth. Moderate evidence supports this finding in cats. In dogs, moderate evidence shows that there is no significant change in heart rate after induction with either alfaxalone-HPCD or propofol. In cats, moderate evidence shows no significant difference in postinduction respiratory rate and heart rate between alfaxalone HPCD and propofol induction. Strong evidence shows dogs and cats have smooth recoveries after induction using either alfaxalone-HPCD or propofol, before reaching sternal recumbency. PMID- 27188882 TI - Description of Teunomyces gen. nov. for the Candida kruisii clade, Suhomyces gen. nov. for the Candida tanzawaensis clade and Suhomyces kilbournensis sp. nov. AB - DNA sequence analysis has shown that species of the Candida kruisii clade and species of the C. tanzawaensis clade represent phylogenetically circumscribed genera, which are described as Teunomyces gen. nov., type species T kruisii, and Suhomyces gen. nov., type species S tanzawaensis Many of the species are distributed worldwide and they are often isolated from fungus-feeding insects and their habitats. Included is the description of S. kilbournensis (type strain NRRL Y-17864, CBS 14276), a species found almost exclusively on maize kernels (Zea mays) in IL, USA. PMID- 27188883 TI - Identification and characterization of Candida utilis multidrug efflux transporter CuCdr1p. AB - The edible, nitrate assimilating, yeast Candida utilis is a commercial food additive, and it is a potentially useful host for heterologous protein expression. A number of ATP-binding cassette (ABC) transporters are multidrug efflux pumps that can cause multidrug resistance in opportunistic pathogens. In order to develop optimal novel antimicrobial agents it is imperative to understand the structure, function and expression of these transporters. With the ultimate aim of developing an alternative yeast host for the heterologous expression of eukaryotic membrane transporters, and to identify ABC transporters potentially associated with C. utilis multidrug resistance, we classified the entire repertoire of 30 C. utilis ABC proteins. We named the open reading frame most similar to the archetype multidrug efflux pump gene C. albicans CDR1 as CuCDR1 Overexpression of CuCDR1 in Saccharomyces cerevisiae ADDelta caused multidrug resistance similar to that of cells overexpressing CaCDR1 Unlike CaCdr1p, however, the C-terminally green fluorescent protein (GFP) tagged CuCdr1p GFP was functionally impaired and did not properly localize to the plasma membrane. CuCdr1p function could be recovered however by adding a 15 amino acid linker -GAGGSAGGSGGAGAG- between CuCdr1p and the C-terminal GFP tag. PMID- 27188884 TI - Genomic analysis and D-xylose fermentation of three novel Spathaspora species: Spathaspora girioi sp. nov., Spathaspora hagerdaliae f. a., sp. nov. and Spathaspora gorwiae f. a., sp. nov. AB - Three novel D-xylose-fermenting yeast species of Spathaspora clade were recovered from rotting wood in regions of the Atlantic Rainforest ecosystem in Brazil. Differentiation of new species was based on analyses of the gene encoding the D1/D2 sequences of large subunit of rRNA and on 642 conserved, single-copy, orthologous genes from genome sequence assemblies from the newly described species and 15 closely-related Debaryomycetaceae/Metschnikowiaceae species. Spathaspora girioi sp. nov. produced unconjugated asci with a single elongated ascospore with curved ends; ascospore formation was not observed for the other two species. The three novel species ferment D-xylose with different efficiencies. Spathaspora hagerdaliae sp. nov. and Sp. girioi sp. nov. showed xylose reductase (XR) activity strictly dependent on NADPH, whereas Sp. gorwiae sp. nov. had XR activity that used both NADH and NADPH as co-factors. The genes that encode enzymes involved in D-xylose metabolism (XR, xylitol dehydrogenase and xylulokinase) were also identified for these novel species. The type strains are Sp. girioi sp. nov. UFMG-CM-Y302(T) (=CBS 13476), Sp. hagerdaliae f.a., sp. nov. UFMG-CM-Y303(T) (=CBS 13475) and Sp. gorwiae f.a., sp. nov. UFMG-CM-Y312(T) (=CBS 13472). PMID- 27188885 TI - MFS transporters of Candida species and their role in clinical drug resistance. AB - ABC (ATP-binding cassette) and MFS (major facilitator superfamily) exporters, belonging to two different superfamilies, are one of the most prominent contributors of multidrug resistance (MDR) in yeast. While the role of ABC efflux pump proteins in the development of MDR is well documented, the MFS transporters which are also implicated in clinical drug resistance have not received due attention. The MFS superfamily is the largest known family of secondary active membrane carriers, and MFS exporters are capable of transporting a host of substrates ranging from small molecules, including organic and inorganic ions, to complex biomolecules, such as peptide and lipid moieties. A few of the members of the drug/H(+) antiporter family of the MFS superfamily function as multidrug transporters and employ downhill transport of protons to efflux their respective substrates. This review focuses on the recent developments in MFS of Candida and highlights their role in drug transport by using the example of the relatively well characterized promiscuous Mdr1 efflux pump of the pathogenic yeast C. albicans. PMID- 27188886 TI - Identification of novel transcriptional regulators of PKA subunits in Saccharomyces cerevisiae by quantitative promoter-reporter screening. AB - The cAMP-dependent protein kinase (PKA) signaling is a broad pathway that plays important roles in the transduction of environmental signals triggering precise physiological responses. However, how PKA achieves the cAMP-signal transduction specificity is still in study. The regulation of expression of subunits of PKA should contribute to the signal specificity. Saccharomyces cerevisiae PKA holoenzyme contains two catalytic subunits encoded by TPK1, TPK2 and TPK3 genes, and two regulatory subunits encoded by BCY1 gene. We studied the activity of these gene promoters using a fluorescent reporter synthetic genetic array screen, with the goal of systematically identifying novel regulators of expression of PKA subunits. Gene ontology analysis of the identified modulators showed enrichment not only in the category of transcriptional regulators, but also in less expected categories such as lipid and phosphate metabolism. Inositol, choline and phosphate were identified as novel upstream signals that regulate transcription of PKA subunit genes. The results support the role of transcription regulation of PKA subunits in cAMP specificity signaling. Interestingly, known targets of PKA phosphorylation are associated with the identified pathways opening the possibility of a reciprocal regulation. PKA would be coordinating different metabolic pathways and these processes would in turn regulate expression of the kinase subunits. PMID- 27188888 TI - Superselective transcatheter arterial embolization in patients with acute peripancreatic bleeding complications: review of 44 cases. AB - PURPOSE: To evaluate the efficacy of superselective transcatheter arterial embolization (TAE) in the treatment of acute peripancreatic bleeding complications. METHODS: During a 9-year period, 44 patients with acute bleeding of the peripancreatic arteries underwent TAE in our institution. Thirty-eight patients were treated using microcatheters and 6 patients with a diagnostic catheter. Embolic agents included coils (n = 38), polyvinyl alcohol (PVA) particles (n = 2), isobutyl cyanoacrylate (n = 2), coils plus PVA particles (n = 1), and coils plus isobutyl cyanoacrylate (n = 1). Outcome measures included technical success, clinical success, and the rate of complications. RESULTS: Identified bleeding sources included gastroduodenal artery (n = 14), splenic artery (n = 9), pancreaticoduodenal artery (n = 6), common hepatic artery (n = 5), superior mesenteric artery branches (n = 4), proper hepatic artery (n = 3), and dorsal/transverse pancreatic artery (n = 3). Technical success with effective control of active bleeding was achieved in 41/44 patients (93 %). Clinical success attributed to TAE alone was documented in 40/44 patients (91 %). The rate of major complications was 2 % including death in one patient. CONCLUSIONS: Superselective TAE allows effective, minimally invasive control of acute peripancreatic bleeding complications with a low rate of therapeutically relevant complications. PMID- 27188889 TI - Response to letter on Caroli disease. PMID- 27188887 TI - Environmental distribution of Cryptococcus neoformans and C. gattii around the Mediterranean basin. AB - In order to elucidate the distribution of Cryptococcus neoformans and C. gattii in the Mediterranean basin, an extensive environmental survey was carried out during 2012-2015. A total of 302 sites located in 12 countries were sampled, 6436 samples from 3765 trees were collected and 5% of trees were found to be colonized by cryptococcal yeasts. Cryptococcus neoformans was isolated from 177 trees and C. gattii from 13. Cryptococcus neoformans colonized 27% of Ceratonia, 10% of Olea, Platanus and Prunus trees and a lower percentage of other tree genera. The 13 C. gattii isolates were collected from five Eucalyptus, four Ceratonia, two Pinus and two Olea trees. Cryptococcus neoformans was distributed all around the Mediterranean basin, whereas C. gattii was isolated in Greece, Southern Italy and Spain, in agreement with previous findings from both clinical and environmental sources. Among C. neoformans isolates, VNI was the prevalent molecular type but VNII, VNIV and VNIII hybrid strains were also isolated. With the exception of a single VGIV isolate, all C. gattii isolates were VGI. The results confirmed the presence of both Cryptococcus species in the Mediterranean environment, and showed that both carob and olive trees represent an important niche for these yeasts. PMID- 27188890 TI - Food preferences, personality and parental rearing styles: analysis of factors influencing health of left-behind children. AB - PURPOSE: To understand the health status and problems of left-behind children (LBC) in rural China, those whose parents have moved to urban areas without them, and to focus on ways to improve their physical and mental health. METHODS: The study examined 827 children between 7 and 15 years old, selected using stratified cluster random sampling from five towns in Xiji County of the Ningxia Hui Autonomous Region. Each child was classified as either LBC or non-LBC. Measures included age- and sex-specific height and body mass index (kg/m2), a food preference questionnaire, the Revised Junior Eysenck Personality Questionnaire, and the Egna Minnen av Barndoms Uppfostran-My Memories of Upbringing (EMBU). RESULTS: Malnutrition rates for LBC and non-LBC were 14.83 % (70/472) and 7.04 % (25/355) (chi 2 = 11.86, p < 0.01). More LBC reported hating vegetables and fruits. Eysenck Personality Questionnaire profiles of LBC revealed a significantly higher degree of neuroticism and psychoticism, and a significantly lower lie scale score (p < 0.01). LBC's EMBU profiles showed that the paternal approach lacked emotional warmth and understanding and the maternal approach was characterized by favoritism, over-interference and overprotection. There were a significant negative correlation between the personality characteristic of neuroticism and liking vegetables and fruits (p < 0.01), and a negative correlation between psychoticism and liking vegetables (p < 0.05). CONCLUSION: The health status of LBC is problematic. Food preferences, personality type and parenting styles should be taken into account when measures are developed to improve the health of these children. PMID- 27188892 TI - Cancer Associated Thrombosis: Focus on Prevention and Treatment of Venous Thromboembolism. AB - Cancer-associated thrombosis (CAT) accounts for about 20% of all thrombosis worldwide. It is the second leading cause of death in cancer patients. The risk of venous thromboembolism (VTE) is 4 -7 times higher and the risk of recurrent VTE three times higher in the cancer patients, compared to the non-cancer patients. The survival of cancer patients with VTE is lower than that of patients without VTE. In the last two decades, the incidence of CAT has risen in the ambulatory patients than in the inpatient setting. While the role of pharmacologic thromboprophylaxis (PTP) is established in the hospitalized cancer patients, ambulatory PTP is not, except in patients with multiple myeloma and myeloproliferative neoplasms. In the last decade, the low-molecular-weight heparin (LMWH) has emerged as the standard of care for the treatment of acute cancer-associated VTE. Many questions remain unanswered with regards to the optimal duration of LMWH therapy in the CAT, the role of direct oral anticoagulants (DOACs) in CAT, and the optimal anticoagulation management in thrombocytopenic cancer patients. Research trials are necessary to define a subset of ambulatory solid tumor patients who may benefit from PTP and to define the role of DOACs in the prevention and treatment of CAT. PMID- 27188891 TI - Increased concentrations of soluble B7-H3 and interleukin 36 in bronchoalveolar lavage fluid of Children with Mycoplasma pneumoniae pneumonia. AB - BACKGROUND: The purpose of this study is to explore the correlations of interleukin 36 (IL-36) and Soluble B7-H3 (sB7-H3) levels in bronchoalveolar lavage fluid (BALF) with clinical characteristics and laboratory findings. METHODS: A total of 35 children with M. pneumnoiae pneumonia (MPP) and 15 control subjects were enrolled. BALF concentrations of sB7-H3 and IL-36 were detected using enzyme-linked immunosorbent assays and clinical profiles of children with MPP were obtained. RESULTS: Children with MPP had significantly higher levels of sB7-H3 and IL-36 compared to control subjects (both P < 0.05). Meanwhile, children with pleural effusion had significantly higher levels of sB7-H3 and IL 36 compared to children without pleural effusion (both P < 0.05). BALF concentration of sB7-H3 was strongly associated with concentration of IL-36 (r = 0.796, P < 0.0001) and sB7-H3 was correlated with duration of fever (r = 0.427, P = 0.11) and length of stay (r = 0.345, P = 0.043). Both concentrations of sB7-H3 and IL-36 were significantly decreased in convalescent phase after treatment (both P < 0.05). CONCLUSION: Both soluble B7-H3 and IL-36 may play an important role in pathogenesis of M. pneumoniae infection and sB7-H3 could be useful as a prognostic predictor or biomarker of MPP. PMID- 27188893 TI - Hematological and Serological Investigation of Dogs during Experimental Echinococcosis. AB - OBJECTIVES: To study the hematological findings of dogs infected with echinococcosis and the possibility of using in vitro reared Echinococcus granulosus excretory-secretory antigen (ES-Ag) as a reagent for serological diagnosis of canine echinococcosis. METHODS: Eight dogs were infected orally with protoscoleces, extracted from ovine fertile hydatid cysts. Two additional dogs were infected with Cysticercus tenuicollis, obtained from infested sheep. The hematological parameters of dogs were determined with the ADVIA 2120i automatic hematology analyzer with a blood smear staining module. Adult E. granulosus and/or Taenia hydatigena that were collected from small pieces of the open gut and the larval cestodes that were extracted from infested sheep during slaughter were cultured in an incomplete RPMI-1640 medium. The parasite-ES-Ag-containing supernatant was used as an antigen in enzyme linked immunosorbent assay (ELISA) to detect antibodies in the sera of infected dogs. RESULTS: A significant increase in hemoglobin concentration and erythrocyte count was found during the infection, as well as an increasing proportion of lymphocytes and segmented neutrophils, accompanied by a significant reduction of the leukocyte count and a growth of both the absolute and the relative eosinophil count. ELISA found a strengthening antigenicity of echinococcus preparations during infection. This property was more pronounced in the protoscoleces ES-Ag, compared to the eponymous antigen of an adult parasite. The latter gave specificity to ELISA, which allowed differentiating it from the similar antigen of the closely related tapeworm T. hydatigena. CONCLUSION: In vitro reared adult E. granulosus ES-Ag can be used as an antigen in the serological diagnosis of canine echinococcosis. Hematological parameters and serological results have predictive value in the screening of dogs for echinococcosis; however, in some individuals, they may reflect the state of resistance to invasion. PMID- 27188894 TI - Measuring Health Literacy Levels of a Patient Portal Using the CDC's Clear Communication Index. AB - Once promised to revolutionize health care, patient portals have yet to fully achieve their potential of improving communication between patients and clinicians. In fact, their use can be detrimental to many consumers due to their limited literacy and numeracy skills. This study demonstrates how applying the Centers for Disease Control and Prevention's Clear Communication Index to a patient portal can be used to identify opportunities for better patient communication and engagement. The Clear Communication Index contains 20 scored items grounded in communication science to enhance patients' understanding of health information. The Index was applied to one portal used by over 80,000 patients in 12 primary care practices: MyPreventiveCare. This portal was selected because of its ability to personalize preventive and chronic care information by internally using content featuring health literacy principles and linking patients' externally to trusted materials. Thirty-seven frequently visited portal pages (17 internal and 20 external) were evaluated based on the Index's four main variables. The overall score for the portal was 72%, which falls below the 90% threshold to be considered clear communication. Internal content scored higher than external (75% vs. 69%). Specific changes to improve the score include simpler language, more specific examples, and clearer numerical explanations. PMID- 27188895 TI - A combination of omega-3 fatty acids, folic acid and B-group vitamins is superior at lowering homocysteine than omega-3 alone: A meta-analysis. AB - The aim of the study was to assess whether omega-3 polyunsaturated fatty acid supplementation alone or in combination with folic acid and B-group vitamins is effective in lowering homocysteine. The Medline Ovid, Embase and Cochrane databases were searched for randomized-controlled trial studies that intervened with omega-3 supplementation (with or without folic acid) and measured changes in homocysteine concentration. Studies were pooled using a random effects model for meta-analysis. Three different models were analyzed: all trials combined, omega-3 polyunsaturated fatty acid trials, and omega-3 polyunsaturated fatty acids with folic acid and B-group vitamin trials. Nineteen studies were included, consisting of 3267 participants completing 21 trials. Studies were heterogeneous; varying by dose, duration and participant health conditions. Across all trials, omega-3 supplementation was effective in lowering homocysteine by an average of 1.18MUmol/L (95%CI: (-1.89, -0.48), P=.001). The average homocysteine-lowering effect was greater when omega-3 supplementation was combined with folic acid and B-group vitamins (-1.37MUmol/L, 95%CI: (-2.38, -0.36), P<.01) compared to omega-3 supplementation alone (-1.09MUmol/L 95%CI: (-2.04, -0.13), P=.03). Omega-3 polyunsaturated fatty acid supplementation was associated with a modest reduction in homocysteine. For the purposes of reducing homocysteine, a combination of omega-3s (0.2-6g/day), folic acid (150 - 2500MUg/day) and vitamins B6 and B12 may be more effective than omega-3 supplementation alone. PMID- 27188897 TI - High dietary calcium intake and a lack of dairy consumption are associated with metabolic syndrome in obese males: the Korean National Health and Nutrition Examination Survey 2010 to 2012. AB - Metabolic syndrome (MetS) has been increasing rapidly worldwide and is associated with elevated risks of cardiovascular disease and mortality. The relationship between MetS and dietary calcium intake is controversial. We hypothesized that high dietary calcium intake is associated with MetS in males and that the associations vary according to obesity status. Using data from the Korean National Health and Nutrition Examination Survey V, a cross-sectional survey of Korean civilians was conducted from January 2010 to December 2012 to test these hypotheses. Data from a total of 5946 males were analyzed with no association observed between dietary calcium intake and the presence of MetS. However, males deriving high calcium intake levels from dairy products had a lower prevalence of MetS than did those who did not ingest such products (adjusted odds ratio [OR], 0.75; 95% confidence interval [CI], 0.58-0.96). In obese males, the highest dietary calcium intake was positively associated with the presence of MetS (adjusted OR, 1.61; 95% CI, 1.12-2.36). However, obese males who consume dairy products had a lower prevalence of MetS than did those who did not consume such products (adjusted OR, 0.51; 95% CI, 0.29-0.90). In conclusion, the results suggest that the high dietary calcium intake, in the absence of dairy product consumption, was associated with the increased prevalence of MetS in obese males. Additional studies are required to determine whether dietary calcium intake affects the development of MetS. PMID- 27188896 TI - Trans fatty acid intake is related to emotional affect in the Adventist Health Study-2. AB - Trans fatty acids in Western diets increase health risks, and have been associated with the risk of depression. We hypothesized that intakes of trans fatty acids (primarily from margarines and baked goods) were inversely associated with positive affect and positively associated with negative affect in a longitudinal study. Church attendees residing in North America completed a food frequency questionnaire in 2002-6 as part of the Adventist Health Study-2. A subset in which we excluded participants with established cardiovascular disease (n=8,771) completed the Positive and Negative Affect Schedule (PANAS) in 2006-7. The associations between dietary intakes of fatty acids to positive and negative affect were tested with linear regression analysis controlling for age, gender, ethnicity, education, body mass index, exercise, sleep, sleep squared, Mediterranean diet, total energy intake and alcohol. Intakes of trans fatty acids were inversely associated with positive affect (beta=-0.06, B=-0.27 [95% CI 0.37, -0.17], p<.001) and positively associated with negative affect (beta=0.05, B=0.21 [95% CI 0.11, 0.31], p<.001). In comparison, we found no association between n-3 polyunsatured fatty acids (PUFA) intakes with affect. The n-6:n-3 PUFA ratio was inversely associated with positive affect (beta=-0.03, B=-0.34 [95% CI -0.58, -0.10], p=0.006). The findings suggest that a lower dietary trans fatty acid intake has beneficial effects on emotional affect while the n-6: n-3 ratio is detrimental to positive affect. PMID- 27188898 TI - Medium-chain triglycerides and conjugated linoleic acids in beverage form increase satiety and reduce food intake in humans. AB - Both developed and developing countries are seeing increasing trends of obesity in people young and old. It is thought that satiety may play a role in the prevention of obesity by increasing satiety and reducing energy intake. We hypothesized that medium-chain triglycerides (MCT) would increase satiety and decrease food intake compared with conjugated linoleic acid (CLA) and a control oil. Nineteen healthy participants were tested on 3 separate occasions, where they consumed a beverage test breakfast containing (1) vegetable oil (control), (2) CLA, or (3) MCT. Participants self-requested an ad libitum sandwich buffet lunch. Time between meals, satiety from visual analog scales, energy intake at lunch, and intake for the rest of the day using weighed food diaries were measured. The results indicated that the time until a meal request was significantly different between the 3 meals (P=.016); however, there were no differences in intakes at the ad libitum lunch (P>.05). The CLA breakfast generated the greatest delay in meal time request. There was a difference between the control lipid compared with both the CLA and MCT for energy intake over the remainder of the test day and for total energy intake on the test day (P<.001 for both), with the CLA and MCT resulting in a lower intake than the control throughout the day. There were no significant differences in satiety from visual analog scale scores (P>.05). Both CLA and MCT increased satiety and reduced energy intake, indicating a potential role in aiding the maintenance of energy balance. PMID- 27188899 TI - Plasma riboflavin is a useful marker for studying riboflavin requirement in Chinese male adults. AB - Urinary riboflavin excretion and erythrocyte glutathione reductase activation coefficient are frequently applied in determining riboflavin requirement. Previously, we found that plasma riboflavin is a sensitive marker in the assessment of riboflavin status in rat models. Here, we hypothesize that plasma riboflavin is a useful maker in studying riboflavin requirement. This study examines the changes of fasting plasma riboflavin and urinary riboflavin excretion in response to different riboflavin intake levels in Chinese male adults. The estimated average requirement (EAR) of riboflavin was extrapolated. Seventy-eight participants were randomly divided into the control and 5 riboflavin-supplemented groups. A 6-week riboflavin supplementation was performed at the doses of 0, 0.2, 0.4, 0.6, 0.8, or 1.0 mg daily. The energy expenditure was 15.4 +/- 1.9 MJ/d, as estimated by the 24-hour physical activity recording method. Dietary riboflavin intake was 1.0 +/- 0.2 mg/d, based on chemical analysis. The fasting plasma riboflavin was increased significantly in a dose dependent manner when the supplemented riboflavin exceeded 0.4 mg/d and the EAR of riboflavin was suggested to be between 1.3 and 1.5 mg/d. In addition, we found a significant increase in fasting urinary riboflavin excretion when the supplemented riboflavin exceeded 0.6 mg/d. The critical point was calculated as 1.4 mg/d, based on the intersecting point of the 2 regression lines at lower and higher riboflavin intakes. These findings demonstrate that plasma riboflavin is a sensitive marker for riboflavin status, and the EAR of riboflavin for Chinese male adults is 1.4 mg. PMID- 27188900 TI - Oat beta-glucan depresses SGLT1- and GLUT2-mediated glucose transport in intestinal epithelial cells (IEC-6). AB - Oat beta-glucan consumption is linked to reduced risk factors associated with diabetes and obesity by lowering glycemic response and serum level of low-density lipoproteins. The purpose of this study was to identify the mechanism of action of oat beta-glucan at the interface between the gut wall and the lumen responsible for attenuating glucose levels. We proposed that viscous oat beta glucan acts as a physical barrier to glucose uptake in normally absorptive gut epithelial cells IEC-6 by affecting the expression of intestinal glucose transporters. Concentration and time-dependent changes in glucose uptake were established by using a nonmetabolizable glucose analog 2-[N-(7-nitrobenz-2-oxa 1,3-diazol-4-yl)amino]-2-deoxy-d-glucose. The effectiveness of nutrient transport in IEC-6 cells was shown by significant differences in glucose uptake and corresponding transporter expression. The expressions of glucose transporters sodium-glucose-linked transport protein 1 (SGLT1) and glucose transporter 2 (GLUT2) increased with time (0-60 minutes) and glucose levels (5-25 mmol/L). The suppression of glucose uptake and SGLT1 and GLUT2 expression by increasing concentrations (4-8 mg/mL) of oat beta-glucan demonstrated a direct effect of the physical properties of oat beta-glucan on glucose transport. These results affirmed oat beta-glucan as a dietary agent for minimizing postprandial glucose and showed that modulating the activity of the key intestinal glucose transporters with oat beta-glucan could be an effective way of lowering blood glucose levels in patients with diabetes. PMID- 27188901 TI - beta-Hydroxy-beta-methylbutyrate attenuates cytokine response during sustained military training. AB - This study tested the hypothesis that of 23 days of beta-hydroxy-beta methylbutyrate (HMB) supplementation can maintain muscle mass and attenuate the immune and inflammatory response in combat soldiers during highly intense military training. Soldiers were randomly assigned to either a HMB (n = 6) or placebo (PL; n = 7) group and provided with 3 g . day(-1) of either HMB or PL. During the final week of supplementation soldiers participated in extreme physical training, which included night navigation of 6-8 hours across difficult terrain carrying heavy loads combined with sleep deprivation (3.8 +/- 3.0 h per night). Blood draws were performed prior to and following the supplementation period. Magnetic resonance imaging, which included diffusion tensor imaging sequence, was used for muscle fiber tracking analysis. Data was analyzed using a two-way mixed factorial analysis of variance. Magnitude-based inferences were used to provide inferences on the true effects that HMB may have had on the dependent variables compared to PL, calculated from 90% confidence intervals. Changes in tumor necrosis factor-alpha for HMB (-3.9 +/- 8.2 pg . mL(-1)) were significantly lower (P = .043) compared to the change in PL (+4.0 +/- 3.7 pg . mL(-1)). HMB ingestion was also very likely (92%-95% Likelihood) to lower granulocyte colony-stimulating factor and interleukin 10 compared to PL. In addition, HMB supplementation was likely (78%-87% likelihood) to reduce interferon-gamma, interleukin 8, CX3CL1, and increase muscle volume for the adductor magnus (77% likelihood) compared to PL. In summary, the results of this study provides evidence that HMB supplementation may attenuate the inflammatory response to high intense military training, and maintain muscle quality. PMID- 27188903 TI - Supplemental arginine above the requirement during suckling causes obesity and insulin resistance in rats. AB - Nutrition in early life is important in determining susceptibility to adult obesity, and arginine may promote growth acceleration in infants. We hypothesized that maternal arginine supplementation may promote growth in their pups and contribute to obesity and alteration of the metabolic system in later life. Dams and pups of Wistar rats were given a normal diet (15% protein) as a control (CN) or a normal diet with 2% arginine (ARG). Altered profiles of free amino acids in breast milk were observed in that the concentrations of threonine and glycine were lower in the ARG dams compared with the CN dams. The offspring of the CN and ARG dams were further subdivided into normal-diet (CN-CN and ARG-CN) groups and a high fat-diet groups (CN-HF and ARG-HF). In response to the high fat-diet feeding, the visceral fat deposits were significantly increased in the ARG-HF group (although not compared with the CN-HF group); no difference was observed between the CN-CN and ARG-CN groups. The blood glucose and insulin levels after glucose loading were significantly higher in the ARG-HF group compared with the CN-HF group. The results suggest that the offspring of dams supplemented with arginine during lactation acquired increased susceptibility to a high-fat diet, resulting in visceral obesity and insulin resistance. The lower supply of threonine and glycine to pups may be one of the contributing causes to the programming of lifelong obesity risk in offspring. Our findings also indicated that maternal arginine supplementation during suckling causes obesity and insulin resistance in rats. PMID- 27188902 TI - The ACTN3 R577X polymorphism affects the lipid profile and the prognosis of nutritional intervention in HIV-positive patients. AB - The hypothesis of the present study is that the polymorphisms in the APOC3, CEPT, ACE, and ACTN3 genes can affect the outcome of nutritional intervention and the plasma lipid profile of HIV+ patients. To test the hypothesis, genetic material was collected from buccal cells, and serum was collected for biochemical analysis. Sixty-five patients were analyzed. The incorporation of protease inhibitor (PI) was more frequent in women (77% vs 33% in men). Nutritional intervention improved anthropometric parameters independent of the genotype. Patients with the RR genotype for the ACTN3 R577X polymorphism had lower glycemia (RR = 95.4 +/- 6.5 mg/dL, RX = 102.6 +/- 10.6 mg/dL, XX = 110.1 +/- 16.3 mg/dL; P = .03) and a greater reduction in low-density lipoproteins (LDL) after intervention (LDL: RR = -23.7 +/- 15.8 mg/dL, RX = 1.32 +/- 5.13 mg/dL, XX = 30.21 +/- 24.4 mg/dL; P = .01). Patients using PI had a negative response to dietary intervention regarding the levels of high-density lipoprotein (-2.4 +/- 1.70 with PI, 2.56 +/- 1.60 mg/dL without PI; P = .02), very low density lipoprotein (0.84 +/- 2.73 with IP, -5.46 +/- 3.37 mg/dL without PI; P = .03), and triglycerides (1.79 +/- 13.22 with PI, -34.00 +/- 17.67 mg/dL without PI; P = .052). This response was also independent of the genotype (P > 0.05) and suggested the need for oral lipid-lowering drugs in all HIV+ patients using PI. Our results indicate that the ACTN3 R577X polymorphism is a good predictor of both the lipid profile and the prognosis of nutritional intervention in reducing LDL in HIV+ patients. PMID- 27188905 TI - Early sugar-sweetened beverage consumption frequency is associated with poor quality of later food and nutrient intake patterns among Japanese young children: the Osaka Maternal and Child Health Study. AB - Evidence from Western countries shows that higher consumption of sugar-sweetened beverages (SSBs) is associated with lower quality of young children's diets, but little is known about these relations in non-Western countries with relatively low consumption levels of SSBs. We hypothesized that SSB consumption in infancy would be associated with poor quality of later food and nutrient intake patterns among Japanese young children. The study subjects were 493 Japanese mother-child pairs from a prospective birth cohort study. Dietary data on children were collected from the mothers using self-administered questionnaires when the children were aged 16-24 months and 41-49 months. Multiple linear regression analyses were used to examine the relationships between SSB consumption frequency in infancy and later intake of foods and nutrients. At 16-24 months of age, more than half of the children (56.4%) consumed SSBs less than once a week, whereas 11.6% consumed SSBs at least once daily. More frequent consumption of SSBs in infancy was associated with higher intake of confectionaries and SSBs and lower intake of fruits and vegetables at 41-49 months of age. These associations were still evident after adjustment for maternal SSB consumption and socioeconomic status. At the nutrient level, SSB consumption frequency was positively associated with energy intake and inversely associated with intake of many nutrients, such as protein, dietary fiber, and most of the micronutrients examined. In conclusion, higher consumption frequency of SSBs at an early age is associated with poor quality of overall dietary intake among young Japanese children 1.5-2.5 years later. PMID- 27188906 TI - Time-restricted feeding reduces adiposity in mice fed a high-fat diet. AB - Disruption of the circadian rhythm contributes to obesity. This study tested the hypothesis that time-restricted feeding (TRF) reduces high-fat diet-induced increase in adiposity. Male C57BL/6 mice were fed the AIN93G or the high-fat diet ad libitum (ad lib); TRF of the high-fat diet for 12 or 8hours during the dark cycle was initiated when high-fat diet-fed mice exhibited significant increases in body weight. Energy intake of the TRF 12-hour group was not different from that of the high-fat ad lib group, although that of the TRF 8-hour group was slightly but significantly lower. Restricted feeding of the high-fat diet reduced body fat mass and body weight compared with mice fed the high-fat diet ad lib. There were no differences in respiratory exchange ratio (RER) among TRF and high fat ad lib groups, but the RER of these groups was lower than that of the AIN93G group. Energy expenditure of the TRF groups was slightly but significantly lower than that of the high-fat ad lib group. Plasma concentrations of ghrelin were increased in TRF groups compared with both AIN93G and high-fat ad lib groups. Elevations of plasma concentrations of insulin, leptin, monocyte chemoattractant protein-1, and tissue inhibitor metalloproteinase-1 by high-fat ad lib feeding were reduced by TRF to the levels of mice fed the AIN93G diet. In conclusion, TRF during the dark cycle reduces high-fat diet-induced increases in adiposity and proinflammatory cytokines. These results indicate that circadian timing of food intake may prevent obesity and abate obesity-related metabolic disturbance. PMID- 27188904 TI - Alternate-day fasting protects the livers of mice against high-fat diet-induced inflammation associated with the suppression of Toll-like receptor 4/nuclear factor kappaB signaling. AB - Because of unhealthy lifestyles, a large number of people are suffering from hepatic lipid accumulation and nonalcoholic steatohepatitis. Energy restriction (ER) is an effective nutritional intervention for preventing chronic disease. However, poor compliance with continuous ER limits its effectiveness. As an alternative to daily ER, alternate-day fasting (ADF) may be more effective. We hypothesized that ADF would improve obesity, hyperglycemia, and insulin resistance and protect the liver against high-fat diet (HFD)-induced steatosis and inflammation. In this study, we used C57BL/6 mice to test the beneficial effects of ADF. Thirty male 6-week-old C57BL/6 mice were divided into 3 groups (10 per group, total N = 30): 1 group was fed chow diet, the second was fed HFD ad libitum, and the third group was submitted to ADF. The mice in the third group were fed the HFD ad libitum every other day and fasted the following day. After 12 months, the mice submitted to ADF exhibited reduced body weights and fasting glucose levels and improved insulin resistance and hepatic steatosis compared with continuous HFD-fed mice. In addition, the serum transaminase levels in the mice of the ADF group were lower than those of the HFD group. Moreover, the ADF regimen suppressed the expression levels of Toll-like receptor 4 and nuclear factor kappaB protein in the liver and suppressed the inflammatory pathway genes interleukin 1beta, tumor necrosis factor alpha, and serum amyloid A. These finding indicate that long-term ADF protects mouse livers against HFD-induced hepatic steatosis and hepatocellular damage associated with the suppression of Toll-like receptor 4/nuclear factor kappaB signaling. PMID- 27188907 TI - Fiber content of diet affects exhaled breath volatiles in fasting and postprandial state in a pilot crossover study. AB - Our pilot study examined the potential of exhaled breath analysis in studying the metabolic effects of dietary fiber (DF). We hypothesized that a high-fiber diet (HFD) containing whole grain rye changes volatile organic compound (VOC) levels in exhaled breath and that consuming a single meal affects these levels. Seven healthy men followed a week-long low-fiber diet (17 g/d) and HFD (44 g/d) in a randomized crossover design. A test meal containing 50 g of the available carbohydrates from wheat bread was served as breakfast after each week. Alveolar exhaled breath samples were analyzed at fasting state and 30, 60, and 120 minutes after this meal parallel to plasma glucose, insulin, and serum lipids. We used solid-phase microextraction and gas chromatography-mass spectrometry for detecting changes in 15 VOCs. These VOCs were acetone, ethanol, 1-propanol, 2 propanol, 1-butanol, acetic acid, propionic acid, butyric acid, valeric acid, isovaleric acid, 2-methylbutyric acid, hexanoic acid, acetoin, diacetyl, and phenol. Exhaled breath 2-methylbutyric acid in the fasting state and 1-propanol at 120 minutes decreased (P = .091 for both) after an HFD. Ingestion of the test meal increased ethanol, 1-propanol, acetoin, propionic acid, and butyric acid levels while reducing acetone, 1-butanol, diacetyl, and phenol levels. Both DF diet content and having a single meal affected breathVOCs. Exploring exhaled breath further could help to develop tools for monitoring the metabolic effects of DF. PMID- 27188908 TI - Associations of red and processed meat with survival among patients with cancers of the upper aerodigestive tract and lung. AB - The effect of red and processed meats on cancer survival is unclear. We sought to examine the role of total and processed red meat consumption on all-cause mortality among patients with cancers of the upper aerodigestive tract (UADT) and lung, in order to test our hypothesis that red or processed meat was associated with overall mortality in these patients. Using data from a population-based case control study conducted in Los Angeles County, we conducted a case-only analysis to examine the association of red or processed meat consumption on mortality after 12 years of follow-up, using a diet history questionnaire. Cox regression was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs), adjusting for potential confounders. Of 601 UADT cancer cases and 611 lung cancer cases, there were 248 and 406 deaths, respectively, yielding crude mortality rates of 0.07 and 0.12 deaths per year. Comparing the highest with lowest quartile of red meat consumption, the adjusted HR was 1.64 (95% CI, 1.04 2.57) among UADT cancer cases; for red or processed meat, the adjusted HR was 1.76 (95% CI, 1.10-2.82). A dose-response trend was observed. A weaker association was observed with red meat consumption and overall mortality among lung cancer cases. In conclusion, this case-only analysis demonstrated that increased consumption of red or processed meats was associated with mortality among UADT cancer cases and WAS weakly associated with mortality among lung cancer cases. PMID- 27188911 TI - Claws, Disorder, and Conformational Dynamics of the C-Terminal Region of Human Desmoplakin. AB - Multicellular organisms consist of cells that interact via elaborate adhesion complexes. Desmosomes are membrane-associated adhesion complexes that mechanically tether the cytoskeletal intermediate filaments (IFs) between two adjacent cells, creating a network of tough connections in tissues such as skin and heart. Desmoplakin (DP) is the key desmosomal protein that binds IFs, and the DP.IF association poses a quandary: desmoplakin must stably and tightly bind IFs to maintain the structural integrity of the desmosome. Yet, newly synthesized DP must traffic along the cytoskeleton to the site of nascent desmosome assembly without "sticking" to the IF network, implying weak or transient DP...IF contacts. Recent work reveals that these contacts are modulated by post translational modifications (PTMs) in DP's C-terminal tail (DPCTT). Using molecular dynamics simulations, we have elucidated the structural basis of these PTM-induced effects. Our simulations, nearing 2 MUs in aggregate, indicate that phosphorylation of S2849 induces an "arginine claw" in desmoplakin's C-terminal tail. If a key arginine, R2834, is methylated, the DPCTT preferentially samples conformations that are geometrically well-suited as substrates for processive phosphorylation by the cognate kinase GSK3. We suggest that DPCTT is a molecular switch that modulates, via its conformational dynamics, DP's overall efficacy as a substrate for GSK3. Finally, we show that the fluctuating DPCTT can contact other parts of DP, suggesting a competitive binding mechanism for the modulation of DP...IF interactions. PMID- 27188910 TI - Electroacupuncture to treat gastroesophageal reflux disease: study protocol for a randomized controlled trial. AB - BACKGROUND: Gastroesophageal reflux disease lowers the quality of life and increases medical costs. Electroacupuncture has been used to ease symptoms and improve gastrointestinal motility in patients with gastroesophageal reflux disease. The main purposes of this study are to evaluate the efficacy and safety of this procedure. METHODS/DESIGN: This is a protocol for a randomized, patient blinded, assessor-blinded, sham-controlled trial. Sixty participants with symptoms of gastroesophageal reflux disease, who have previously undergone standard treatment, will be recruited from August 2015 at Kyung Hee University Korean Medicine Hospital. The participants will be allocated to either the electroacupuncture (n = 30) or the sham electroacupuncture group (n = 30); the allocation will be concealed from both the participants and the assessors. The EA group will undergo penetrating acupuncture at 18 fixed points and two optional points chosen using the pattern identification for gastroesophageal reflux disease. Electrical stimulation will be applied at some of the acupoints. The sham electroacupuncture group will undergo nonpenetrating acupuncture without electrical stimulation at 18 nonspecific points, each of which will be only 2 cm away from the true acupoints used in the electroacupuncture group. In both groups, the procedure will be performed using the Park device. The treatment will last for 6 weeks (with two sessions each week), and the outcome will be evaluated at baseline, 3 weeks, and 6 weeks. The primary outcome will be the proportion of responders with adequate symptom relief, whereas the secondary outcomes will comprise the results of the Nepean dyspepsia index; the Korean gastrointestinal symptom rating scale; the EQ-5DTM; levels of gastrin, motilin, and inflammatory cytokines; the perceived stress scale; the qi-stagnation questionnaire; the patient global impression of change; and the spleen qi deficiency questionnaire. DISCUSSION: The results of this trial will provide information about the efficacy and safety of electroacupuncture in the treatment of gastroesophageal reflux disease symptoms, as well as evidence regarding the use of electroacupuncture to treat gastroesophageal reflux disease in real clinical practice. TRIAL REGISTRATION: Clinical Research Information Service Identifier, KCT0001653 . Registered on 12 October 2015. PMID- 27188909 TI - Fibroblasts and Mesenchymal Stromal/Stem Cells Are Phenotypically Indistinguishable. AB - BACKGROUND/AIMS: Human mesenchymal stromal/stem cells (MSCs), derived from many different tissues, are characterized by a fibroblast-like morphology, the expression of certain cell surface markers and their ability to differentiate into adipocytes, chondrocytes and osteoblasts. A number of studies have shown that MSCs share many characteristics with fibroblasts; however, there is no well defined set of phenotypic characteristics that could distinguish between these 2 types of cells. METHODS: We used 4 well-established human fibroblast strains from 3 different tissue sources and several human MSC strains from 2 different tissue sources to compare the phenotypic and immunological characteristics of these cells. RESULTS: Fibroblast strains had a similar morphology to MSCs, expressed the same cell surface markers as MSCs and could also differentiate into adipocytes, chondrocytes and osteoblasts. Also, similar to MSCs, these fibroblasts were capable of suppressing T cell proliferation and modulating the immunophenotype of macrophages. We also show that MSCs deposit extracellular matrices of collagen type I and fibronectin, and express FSP1 in patterns similar to fibroblasts. CONCLUSIONS: Based on currently accepted definitions for cultured human MSCs and fibroblasts, we could not find any immunophenotypic property that could make a characteristic distinction between MSCs and fibroblasts. PMID- 27188912 TI - Bacillus Calmette-Guerin-inoculation at different time points influences the outcome of C57BL/6 mice infected with Plasmodium chabaudi chabaudi AS. AB - Bacillus Calmette-Guerin (BCG) is an attenuated Mycobacterium tuberculosis vaccine. We performed a series of co-infection experiments with BCG-Plasmodium chabaudi chabaudi Landau, 1965 AS using C57BL/6 mice to analyse whether BCG can affect the development of protective immunity to infection with Plasmodium spp. and the mechanism of this protection. We divided mice into four groups: BCG inoculation 4 weeks prior to P. c. chabaudi AS infection (B-4w-Pc); simultaneous BCG-inoculation and P. c. chabaudi AS infection (Pc+B); BCG-inoculation 3 days post P. c. chabaudi AS (Pc-3-B) infection; and mono-P. c. chabaudi AS infection as control (Pc). The parasitemia level in the B-4w-Pc group was noticeably higher than control group at 6-19 days post infection (dpi). Compared with the control group, the proportion of CD4(+)CD69(+) T cells was significantly reduced 5, 8 and 12 dpi, but the proportion of CD4(+)CD25(+)Foxp3(+) Tregs was significantly increased in the B-4w-Pc group on 5 and 8 dpi. The B-4w-Pc group also demonstrated reduced levels of IFN-gamma and TNF-alpha on 5 and 8 dpi and significantly elevated level of IL-10 on 12 dpi. There were significantly fewer mDCs (CD11c(+)CD11b(+)) and pDCs (CD11c(+)B220(+)) in the B-4w-Pc group than the control group at all the time points post infection and the expression of MHC II was noticeably reduced on day 8 pi. Our findings confirmed that BCG inoculation prior to Plasmodium infection resulted in excessive activation and proliferation of Tregs and upregulation of anti-inflammatory mediators, which inhibited establishment of a Th1-dominant immune response during the early stages of Plasmodium infection by inhibiting dendritive cells response. BCG inoculation prior to P. c. chabaudi AS infection may contribute to overgrowth of parasites as well as mortality in mice. PMID- 27188914 TI - Harnessing Lewis acidic open metal sites of metal-organic frameworks: the foremost route to achieve highly selective benzene sorption over cyclohexane. AB - pi-Complexation triggered Lewis acid-base interactions between open metal sites (OMS) of metal-organic frameworks (MOFs), and pi-e(-) rich adsorptive benzene (Bz) is exploited to establish M-MOF-74 as the best Bz-selective MOF sorbent, marking the first report of utilizing OMS behind benzene/cyclohexane separation; a key advance from the energy-economy standpoint of industrial separation. PMID- 27188913 TI - Transthyretin Cardiac Amyloidosis in Black Americans. AB - Transthyretin-related cardiac amyloidosis is a progressive infiltrative cardiomyopathy that mimics hypertensive and hypertrophic heart disease and often goes undiagnosed. In the United States, the hereditary form disproportionately afflicts black Americans, who when compared with whites with wild-type transthyretin amyloidosis, a phenotypically similar condition, present with more advanced disease despite having a noninvasive method for early identification (genetic testing). Although reasons for this are unclear, this begs to consider the inadequate access to care, societal factors, or a biological basis. In an effort to improve awareness and explore unique characteristics, we review the pathophysiology, epidemiology, and therapeutic strategies for transthyretin amyloidosis and highlight diagnostic pitfalls and clinical pearls for identifying patients with amyloid heart disease. PMID- 27188915 TI - Liver-related safety assessment of green tea extracts in humans: a systematic review of randomized controlled trials. AB - There remain liver-related safety concerns, regarding potential hepatotoxicity in humans, induced by green tea intake, despite being supposedly beneficial. Although many randomized controlled trials (RCTs) of green tea extracts have been reported in the literature, the systematic reviews published to date were only based on subjective assessment of case reports. To more objectively examine the liver-related safety of green tea intake, we conducted a systematic review of published RCTs. A systematic literature search was conducted using three databases (PubMed, EMBASE and Cochrane Central Register of Controlled Trials) in December 2013 to identify RCTs of green tea extracts. Data on liver-related adverse events, including laboratory test abnormalities, were abstracted from the identified articles. Methodological quality of RCTs was assessed. After excluding duplicates, 561 titles and abstracts and 119 full-text articles were screened, and finally 34 trials were identified. Of these, liver-related adverse events were reported in four trials; these adverse events involved seven subjects (eight events) in the green tea intervention group and one subject (one event) in the control group. The summary odds ratio, estimated using a meta-analysis method for sparse event data, for intervention compared with placebo was 2.1 (95% confidence interval: 0.5-9.8). The few events reported in both groups were elevations of liver enzymes. Most were mild, and no serious liver-related adverse events were reported. Results of this review, although not conclusive, suggest that liver related adverse events after intake of green tea extracts are expected to be rare. PMID- 27188916 TI - Iodine nutrition status and thyroid disorders: a cross-sectional study from the Xinjiang Autonomous Region of China. AB - BACKGROUND/OBJECTIVES: Iodine nutritional status and its influence on thyroid function have been thoroughly investigated in many places in China, but little is known about Xinjiang province, where multiple minorities are living in a special geographical location and have different lifestyles compared with people from other parts of China. The aim of this study was to evaluate iodine status and thyroid disorders in two major ethnic groups living in the Xinjiang region of China. SUBJECTS/METHODS: A total of 2253 residents over the age of 18 years who had lived in Xinjiang for more than 3 years were enrolled. Urinary iodine concentration (UIC), serum thyroid hormone concentrations and thyroid autoantibodies were measured, and thyroid ultrasonography was performed. RESULTS: The median UIC was 130.7 MUg/l in adults. Among the subjects, those with deficient UIC levels were 34.4%. The prevalence of overt hyper- and hypothyroidism in the iodine-deficient group was higher than in the iodine sufficient group (1.3% vs 0%, chi2=3.891, P=0.049; 4.8% vs 2.8%, chi2=8.715, P=0.003, respectively), and subclinical hypothyroidism was more frequent in the iodine-deficient group than in the iodine-excess group (19.6% vs 12.5%, chi2=4.529, P=0.033). CONCLUSIONS: One-third of the population is still iodine deficient in Xinjiang. Uyghur females are more susceptible to hypothyroidism and thyroid autoimmune diseases. Thyroid disorders, especially hyper/hypothyroidism and subclinical hypothyroidism, are more likely to be prevalent in an iodine deficient population. PMID- 27188917 TI - Effects of two therapeutic dietary regimens on primary chylomicronemia in paediatric age: a retrospective data analysis. AB - BACKGROUND/OBJECTIVE: Subjects suffering from lipoprotein lipase (LPL) deficiency show very severe hypertriglyceridemia, often accompanied by recurrent bouts of pancreatitis. Dietary intervention is currently considered first-line treatment of this condition in paediatric age. The aim of our study was to compare the effects of dietary treatment with a low-fat diet alone and a low-fat diet enriched with omega-3-fatty acids. SUBJECTS/METHODS: The data of 11 patients with LPL deficiency who were diagnosed in our lipid clinic between October 1997 and October 2007 were summarised. All patients had been treated with a low-fat diet, and in addition a group of five patients received supplements of omega-3-fatty acids over a period of at least 5 months. RESULTS: After adjustment for pre intervention TG concentration, there was a statistically significant difference in post-intervention TG concentrations between the interventions, F(1,8)=13.529, P=0.006, partial eta2=0.628. Post-intervention-adjusted TG concentrations were statistically significantly greater in the low-fat diet group vs the w3 diet group (P <0.05). CONCLUSIONS: We provide first evidence that a low-fat diet supplemented with omega-3-fatty acids results in a pronounced decrease in TG in paediatric patients affected with LPL deficiency. However, further studies are necessary to evaluate the long-term effects and safety of omega-3-fatty acids. PMID- 27188918 TI - Perception of lactose intolerance impairs health-related quality of life. AB - BACKGROUND/OBJECTIVES: Chronic conditions impair perception of well-being. Malabsorption of lactose is the most frequent form of malabsorption and manifests as lactose intolerance. There is a lack of information regarding their impact on self-perception of health. The objective of this study is to determine the subjective impact of self-reported lactose intolerance or objective lactose malabsorption on patient health by using a patient-reported outcome to measure health-related quality of life (HRQOL) and modification of lactose-containing food diet. SUBJECTS/METHODS: A 3-year prospective, cross-sectional study was performed in patients referred for a lactose hydrogen breath test. Patients were asked about their subjective opinion relative to their lactose tolerance and completed a validated, specific questionnaire to determine symptoms of intolerance during habitual consumption of dairy. A 50-g lactose breath test was then performed. Patients were grouped as absorbers vs malabsorbers and tolerant vs intolerants. RESULTS: A total of 580 patients were included (median age 30 years, 419 female). Overall, 324 patients (56%) considered themselves lactose intolerant and that perception was associated with avoidance of dairy consumption (55% vs only 9% of self-defined tolerants). Self-perception of intolerance was associated with lower HRQOL scores (median, 60 vs 70, P<0.01). In contrast, lactose objective malabsorption was not clearly associated with dairy avoidance (41% of malabsorbers avoided dairy vs 31% of absorbers). However, HRQOL scores were also significantly lower in malabsorbers than in absorbers (60 vs 70 respectively, P<0.001). CONCLUSIONS: Subjective perception of lactose intolerance affects the decision to avoid dairy even more than objective malabsorption. However, both self-perception of lactose intolerance and objective lactose malabsorption are associated with poorer perceived quality of life. PMID- 27188919 TI - Incidence of gastroesophageal reflux associated with percutaneous endoscopic gastrostomy contrast agent viscosity: a randomized controlled crossover trial. AB - BACKGROUND/OBJECTIVES: Semisolid formulae are increasingly used in Japan to reduce the risks of gastroesophageal reflux (GER) and aspiration pneumonia in patients undergoing percutaneous endoscopic gastrostomy (PEG). We compared the incidences of GER after the use of liquid or semisolid contrast agents during PEG. SUBJECTS/METHODS: Patients who planned to undergo PEG were randomly assigned to the liquid-first (LF) group (liquid contrast agent on day 1 after PEG and a semisolid contrast agent on day 2) or the semisolid-first (SF) group (reversed order). A 200-ml agent bolus was administered via a PEG tube to the patient in the supine position. The upper gastrointestinal tract was radiologically examined from onset to 1 min after the end of administration. The incidences of GER were compared. We also evaluated the daily changes in GER incidence, effect of hiatal hernia severity and adverse events. RESULTS: We analyzed the results of 66 patients (32, LF group; 34, SF group). The incidence of GER observed using only liquid contrast was 27% (18/66) and that using only semisolid was 11% (7/66) (P=0.028). There was no difference in the GER incidences between day 1 and day 2. In patients with severe, mild and no hiatal hernia, GER incidences in the liquid contrast agent were 80% (4/5), 61% (11/18) and 33% (13/43), respectively (P=0.031). GER incidence after using the semisolid contrast agent was lower in patients with no and mild hiatal hernia. The predominant adverse event was diarrhea; aspiration was not observed. CONCLUSIONS: Semisolid contrast agents reduced the incidence of GER after PEG. PMID- 27188920 TI - Engineering and Characterization of Peptides and Proteins at Surfaces and Interfaces: A Case Study in Surface-Sensitive Vibrational Spectroscopy. AB - Understanding molecular structures of interfacial peptides and proteins impacts many research fields by guiding the advancement of biocompatible materials, new and improved marine antifouling coatings, ultrasensitive and highly specific biosensors and biochips, therapies for diseases related to protein amyloid formation, and knowledge on mechanisms for various membrane proteins and their interactions with ligands. Developing methods for measuring such unique systems, as well as elucidating the structure and function relationship of such biomolecules, has been the goal of our lab at the University of Michigan. We have made substantial progress to develop sum frequency generation (SFG) vibrational spectroscopy into a powerful technique to study interfacial peptides and proteins, which lays a foundation to obtain unique and valuable insights when using SFG to probe various biologically relevant systems at the solid/liquid interface in situ in real time. One highlighting feature of this Account is the demonstration of the power of combining SFG with other techniques and methods such as ATR-FTIR, surface engineering, MD simulation, liquid crystal sensing, and isotope labeling in order to study peptides and proteins at interfaces. It is necessary to emphasize that SFG plays a major role in these studies, while other techniques and methods are supplemental. The central role of SFG is to provide critical information on interfacial peptide and protein structure (e.g., conformation and orientation) in order to elucidate how surface engineering (e.g., to vary the structure) can ultimately affect surface function (e.g., to optimize the activity). This Account focuses on the most significant recent progress in research on interfacial peptides and proteins carried out by our group including (1) the development of SFG analysis methods to determine orientations of regular as well as disrupted secondary structures, and the successful demonstration and application of an isotope labeling method with SFG to probe the detailed local structure and microenvironment of peptides at buried interfaces, (2) systematic research on cell membrane associated peptides and proteins including antimicrobial peptides, cell penetrating peptides, G proteins, and other membrane proteins, discussing the factors that influence interfacial peptide and protein structures such as lipid charge, membrane fluidity, and biomolecule solution concentration, and (3) in-depth discussion on solid surface immobilized antimicrobial peptides and enzymes. The effects of immobilization method, substrate surface, immobilization site on the peptide or protein, and surrounding environment are presented. Several examples leading to high impact new research are also briefly introduced: The orientation change of alamethicin detected while varying the model cell membrane potential demonstrates the feasibility to apply SFG to study ion channel protein gating mechanisms. The elucidation of peptide secondary structures at liquid crystal interfaces shows promising results that liquid crystal can detect and recognize different peptides and proteins. The method of retaining the native structure of surface immobilized peptides or proteins in air demonstrates the feasibility to protect and preserve such structures via the use of hydromimetic functionalities when there is no bulk water. We hope that readers in many different disciplines will benefit from the research progress reported in this Account on SFG studies of interfacial structure-function relationships of peptides and proteins and apply this powerful technique to study interfacial biomolecules in the future. PMID- 27188921 TI - Diabetic kidney disease. AB - The kidney is arguably the most important target of microvascular damage in diabetes. A substantial proportion of individuals with diabetes will develop kidney disease owing to their disease and/or other co-morbidity, including hypertension and ageing-related nephron loss. The presence and severity of chronic kidney disease (CKD) identify individuals who are at increased risk of adverse health outcomes and premature mortality. Consequently, preventing and managing CKD in patients with diabetes is now a key aim of their overall management. Intensive management of patients with diabetes includes controlling blood glucose levels and blood pressure as well as blockade of the renin angiotensin-aldosterone system; these approaches will reduce the incidence of diabetic kidney disease and slow its progression. Indeed, the major decline in the incidence of diabetic kidney disease (DKD) over the past 30 years and improved patient prognosis are largely attributable to improved diabetes care. However, there remains an unmet need for innovative treatment strategies to prevent, arrest, treat and reverse DKD. In this Primer, we summarize what is now known about the molecular pathogenesis of CKD in patients with diabetes and the key pathways and targets implicated in its progression. In addition, we discuss the current evidence for the prevention and management of DKD as well as the many controversies. Finally, we explore the opportunities to develop new interventions through urgently needed investment in dedicated and focused research. For an illustrated summary of this Primer, visit: http://go.nature.com/NKHDzg. PMID- 27188922 TI - PPVT-I administration rules significantly shorten PPVT-III/IV administration. AB - This study evaluated whether using the Peabody Picture Vocabulary Test-First Edition (PPVT-I) basal and ceiling criteria would result in similar estimates of receptive vocabulary while permitting administration of fewer test items when using the third and fourth editions of the PPVT. Data were retrospectively collected from 119 adult inpatients who completed a neuropsychological screen that included the PPVT-III or PPVT-IV, which were re-scored using PPVT-I criteria. PPVT-III/IV raw scores were not significantly different from PPVT-I raw scores. Although the difference between the PPVT-III/IV and PPVT-I standard scores was statistically significant, the difference was less than 8 points in 95% of cases. On average, 15 fewer items would be administered using the PPVT-I rules, leading to shorter administration time. PMID- 27188924 TI - Between fighting and tolerance: reproductive biology of wingless males in the ant Cardiocondyla venustula. AB - Male reproductive tactics vary widely across the species of the ant genus Cardiocondyla, from obligatory lethal combat among co-occurring males to complete mutual tolerance. The African species C. venustula Wheeler, 1908 has an intermediate phylogenetic position between taxa with fighting males and taxa with tolerant males and also shows an intermediate male behavior. Males from 2 native populations in South Africa and a population introduced to Puerto Rico attacked and killed freshly eclosing rivals but rarely engaged in deadly fights with adult competitors. Instead, several males per colony established small "territories" in their natal nests and defended them against other males. Males with a stable territory had more contact with female sexuals than nonterritorial males and more frequently engaged in mating attempts. In controlled choice experiments, female sexuals did not show any preference for particular males. We suggest that male territoriality in C. venustula is an adaptation to the seasonal production of large numbers of female sexuals by multiple mothers. PMID- 27188925 TI - Ag2S atomic switch-based 'tug of war' for decision making. AB - For a computing process such as making a decision, a software controlled chip of several transistors is necessary. Inspired by how a single cell amoeba decides its movements, the theoretical 'tug of war' computing model was proposed but not yet implemented in an analogue device suitable for integrated circuits. Based on this model, we now developed a new electronic element for decision making processes, which will have no need for prior programming. The devices are based on the growth and shrinkage of Ag filaments in alpha-Ag2+deltaS gap-type atomic switches. Here we present the adapted device design and the new materials. We demonstrate the basic 'tug of war' operation by IV-measurements and Scanning Electron Microscopy (SEM) observation. These devices could be the base for a CMOS free new computer architecture. PMID- 27188926 TI - Structural traits and catalytic versatility of the lipases from the Candida rugosa-like family: A review. AB - Lipases and sterol esterases are enzymes with broad biotechnological applications, which catalyze the hydrolysis or synthesis of long-chain acylglycerols and sterol esters, respectively. In this paper, we review the current knowledge on the so-called Candida rugosa-like family of enzymes, whose members display in most cases affinity against the two substrates mentioned above. The family includes proteins with the alpha/beta-hydrolase folding, sharing conserved motifs in their sequences, and common structural features. We will go through their production and purification, relate their described structures and catalytic activity, and discuss the influence of the hydrophobic character of these lipases on their aggregation state and activity. On the basis of the few crystal structures available, the role of each of the functional areas in catalysis will be analyzed. Considering the particular characteristics of this group, we propose their classification as "Versatile Lipases" (EC 3.1.1.x). PMID- 27188927 TI - MALDI mass spectrometry imaging: A cutting-edge tool for fundamental and clinical histopathology. AB - Histopathological diagnoses have been done in the last century based on hematoxylin and eosin staining. These methods were complemented by histochemistry, electron microscopy, immunohistochemistry (IHC), and molecular techniques. Mass spectrometry (MS) methods allow the thorough examination of various biocompounds in extracts and tissue sections. Today, mass spectrometry imaging (MSI), and especially matrix-assisted laser desorption ionization (MALDI) imaging links classical histology and molecular analyses. Direct mapping is a major advantage of the combination of molecular profiling and imaging. MSI can be considered as a cutting edge approach for molecular detection of proteins, peptides, carbohydrates, lipids, and small molecules in tissues. This review covers the detection of various biomolecules in histopathological sections by MSI. Proteomic methods will be introduced into clinical histopathology within the next few years. PMID- 27188928 TI - The usefulness of neutrophil CD64 expression for diagnosing infection after orthopaedic surgery in dialysis patients. AB - BACKGROUND: Dialysis patients undergoing orthopaedic surgery are at high risk for postoperative infection. Diagnosis of postoperative infection is difficult in dialysis patients due to presentation of signs and symptoms similar to infection, such as fever and elevated inflammatory marker levels. Neutrophil CD64 expression (CD64), a marker of infection, is upregulated by microbial wall components and several cytokines (interferon-gamma and tumor necrosis factor-alpha). The purpose of this study is to evaluate the usefulness of CD64 for diagnosing postoperative infection in dialysis patients post orthopaedic surgery. PATIENTS AND METHODS: Between 2013 and 2014, we prospectively studied 36 dialysis patients (18 men, 18 women; mean age 65.9 years; 49 to 83) who underwent orthopaedic surgery. Dialysis patients were classified into three groups according to their postoperative course as follows; non-infected patients, infection suspected patients, and infected patients. Inflammatory markers such as white blood cell count (WBC), C reactive protein (CRP) and CD64 were measured before operation and one week after surgery. Using the receiver-operating characteristic (ROC) curve and Akaike's Information Criterion (AIC), the cutoff value of CD64 and CRP was calculated leading to a determination of which inflammatory marker is best accurate for detecting postoperative infection. RESULTS: We found that postoperative CD64 and CRP levels presented a statistically significant difference between infected patients and non-infected patients (p < 0.05). Furthermore, comparison of the ROC curve and AIC value between postoperative CD64 and CRP levels exhibited that CD64 was more accurate infectious marker than CRP. CONCLUSION: CD64 is a useful marker for detecting postoperative infection after orthopaedic surgery in dialysis patients. PMID- 27188929 TI - Enough positive rate of paraspinal mapping and diffusion tensor imaging with levels which should be decompressed in lumbar spinal stenosis. AB - INTRODUCTION: In lumbar spinal stenosis, correlating symptoms and physical examination findings with decompression levels based on common imaging is not reliable. Paraspinal mapping (PM) and diffusion tensor imaging (DTI) may be possible to prevent the false positive occurrences with MRI and show clear benefits to reduce the decompression levels of lumbar spinal stenosis than conventional magnetic resonance imaging (MRI) + neurogenic examination (NE). However, they must have enough positive rate with levels which should be decompressed at first. The study aimed to confirm that the positive of DTI and PM is enough in levels which should be decompressed in lumbar spinal stenosis. MATERIALS AND METHODS: The study analyzed the positive of DTI and PM as well as compared the preoperation scores to the postoperation scores, which were assessed preoperatively and at 2 weeks, 3 months 6 months, and 12 months postoperatively. RESULTS: 96 patients underwent the single level decompression surgery. The positive rate among PM, DTI, and (PM or DTI) was 76%, 98%, 100%, respectively. All post-operative Oswestry Disability Index (ODI), visual analog scale for back pain (VAS-BP) and visual analog scale for leg pain (VAS-LP) scores at 2 weeks postoperatively were measured improvement than the preoperative ODI, VAS-BP and VAS-LP scores with statistically significance (p-value = 0.000, p-value = 0.000, p-value = 0.000, respectively). CONCLUSIONS: In degenetive lumbar spinal stenosis, the positive rate of (DTI or PM) is enough in levels which should be decompressed, thence using the PM and DTI to determine decompression levels will not miss the level which should be operated. PMID- 27188930 TI - Comparison of fixation properties between coil-type and screw-type anchors for rotator cuff repair: A virtual pullout testing using 3-dimensional finite element method. AB - BACKGROUND: Pullout of inserted anchor constitutes one of the pathomechanisms of re-tearing after rotator cuff repair. The purpose of the present study was to investigate the fixation properties of suture anchors using 3-dimensional finite element method. METHODS: The computer models of three types of anchors (TwinFix Ti, HEALICOIL PK and HEALICOIL RG) were inserted into the isotropic cube model that simulated cancellous bone. In the virtual pullout testing, a tensile load (500 N) along the long axis of the inserted anchor was applied to the site of suture thread attachment to simulate a traction force. The distribution of von Mises equivalent stress, the failure patterns of elements inside the cube and the anchor displacement were compared among the three anchors. RESULTS: In TwinFix Ti, the highest stress concentration was seen around the anchor threads close to the surface of the cube, which caused element failure at this site. On the other hand, both HEALICOIL PK and HEALICOIL RG demonstrated a high stress concentration as well as element failure around the anchor tip. Comparing the anchor displacement, HEALICOIL RG showed the smallest displacement among the three anchors. The tensile loads that required a 0.1-mm displacement for TwinFix Ti, HEALICOIL PK and HEALICOIL RG were 400 N, 370 N, and greater than 500 N, respectively. CONCLUSIONS: The bony structures close to the footprint surface may be damaged during surgery due to preparation for the bony bed as well as the insertion of anchors. Thus, we assumed that HEALICOIL RG represented the best initial fixation properties among the three anchors tested. Virtual pullout testing using 3-dimensional finite element method could reveal the detailed biomechanical characteristics of each suture anchor, which would be important for shoulder surgeons to improve the clinical outcomes of rotator cuff repair. PMID- 27188931 TI - A novel protocol to test age-related decreases in sit-to-stand movement abilities in healthy subjects. AB - BACKGROUND: The development of simple approaches to quantitatively estimate functional motor performance in a wide range of ages is crucial for early detection of locomotive syndrome (LS). Sit-to-stand (STS) movements from a chair are important in activities of daily living (ADL), although such tasks are the most mechanically demanding among all ADL. Here, we propose a novel test to score STS abilities to estimate individual functional motor status and investigated age related changes in STS scores as a method to evaluate reduction in performance. METHODS: A total of 606 healthy subjects (average age, 48.4 years; age range, 20 87 years) without neuromusculoskeletal disorders participated in the study. We designed a test to score STS abilities, based on STS determinant variables, including seat height, foot positioning, and both-leg- or one-leg-standing tasks. STS scores ranged from 0 to 14 points, depending on the difficulty or mechanical demands of the STS task. We evaluated the STS score of the subjects divided into seven 10-year age groups. RESULTS: A significant and negative correlation was observed between STS scores and subject age (men: r = -0.65, P < 0.001; women: r = -0.62, P < 0.001). The proportion of subjects able to stand on one leg from a chair seat height of 100% of knee height decreased with age from 100% for both men and women aged 20-29 years to 0.0% and 7.1% for men and women aged 80-87 years, respectively. A large variation in STS scores was observed for subjects aged >60 years. There was a negative linear correlation between mean STS score per age group and mean age (men: R(2) = 0.93, slope = -0.10, intercept = 16.63 points; women: R(2) = 0.92, slope = -0.08, intercept = 14.76 points). CONCLUSIONS: The ability to perform STS was negatively correlated with age among healthy subjects aged 20-87 years. For subjects aged >60 years, STS abilities decreased, but within-group variability increased. This test was useful to identify the deterioration of functional motor performance and prevent early LS. PMID- 27188933 TI - "It's not my organization, it's ours". PMID- 27188932 TI - A high intrapatient variability in tacrolimus exposure is associated with poor long-term outcome of kidney transplantation. AB - Tacrolimus is a critical dose drug with a considerable intrapatient variability (IPV) in its pharmacokinetics. We investigated whether a high IPV in tacrolimus exposure is associated with adverse long-term renal transplantation outcomes. Tacrolimus IPV was calculated from predose concentrations measured between 6 and 12 months post-transplantation of 808 renal transplant recipients (RTRs) transplanted between 2000 and 2010. One hundred and eighty-eight (23.3%) patients reached the composite end point consisting of graft loss, late biopsy-proven rejection, transplant glomerulopathy, or doubling of serum creatinine concentration between month 12 and the last follow-up. The cumulative incidence of the composite end point was significantly higher in patients with high IPV than in patients with low IPV (hazard ratio: 1.41, 95% CI: 1.06-1.89; P = 0.019). After the adjustment for several factors, the higher incidence of the composite end point for RTRs with a high IPV remained statistically significant (hazard ratio: 1.42, 95% CI: 1.06-1.90; P = 0.019). Younger recipient age at transplantation, previous transplantation, worse graft function (at month 6 post transplantation), and low mean tacrolimus concentration at 1 year post transplantation were additional predictors for worse long-term transplant outcome. A high tacrolimus IPV is an independent risk factor for adverse kidney transplant outcomes that can be used as an easy monitoring tool to help identify high-risk RTRs. PMID- 27188934 TI - Alzheimer's disease. AB - Alzheimer's disease is a chronic illness with long preclinical and prodromal phases (20 years) and an average clinical duration of 8-10 years. The disease has an estimated prevalence of 10-30% in the population >65 years of age with an incidence of 1-3%. Most patients with Alzheimer's disease (>95%) have the sporadic form, which is characterized by a late onset (80-90 years of age), and is the consequence of the failure to clear the amyloid-beta (Abeta) peptide from the interstices of the brain. A large number of genetic risk factors for sporadic disease have been identified. A small proportion of patients (<1%) have inherited mutations in genes that affect processing of Abeta and develop the disease at a much younger age (mean age of ~45 years). Detection of the accumulation of Abeta is now possible in preclinical and prodromal phases using cerebrospinal fluid biomarkers and PET. Several approved drugs ameliorate some of the symptoms of Alzheimer's disease, but no current interventions can modify the underlying disease mechanisms. Management is focused on the support of the social networks surrounding the patient and the treatment of any co-morbid illnesses, such as cerebrovascular disease. PMID- 27188935 TI - Association of Genetic Risk for Schizophrenia With Nonparticipation Over Time in a Population-Based Cohort Study. AB - Progress has recently been made in understanding the genetic basis of schizophrenia and other psychiatric disorders. Longitudinal studies are complicated by participant dropout, which could be related to the presence of psychiatric problems and associated genetic risk. We tested whether common genetic variants implicated in schizophrenia were associated with study nonparticipation among 7,867 children and 7,850 mothers from the Avon Longitudinal Study of Parents and Children (ALSPAC; 1991-2007), a longitudinal population cohort study. Higher polygenic risk scores for schizophrenia were consistently associated with noncompletion of questionnaires by study mothers and children and nonattendance at data collection throughout childhood and adolescence (ages 1-15 years). These associations persisted after adjustment for other potential correlates of nonparticipation. Results suggest that persons at higher genetic risk for schizophrenia are likely to be underrepresented in cohort studies, which will underestimate risk of this and related psychiatric, cognitive, and behavioral phenotypes in the population. Statistical power to detect associations with these phenotypes will be reduced, while analyses of schizophrenia-related phenotypes as outcomes may be biased by the nonrandom missingness of these phenotypes, even if multiple imputation is used. Similarly, in complete-case analyses, collider bias may affect associations between genetic risk and other factors associated with missingness. PMID- 27188937 TI - Associations of Blood Pressure With Geographical Latitude, Solar Radiation, and Ambient Temperature: Results From the Chilean Health Survey, 2009-2010. PMID- 27188936 TI - Measures of Body Size and Composition and Risk of Incident Atrial Fibrillation in Older People: The Cardiovascular Health Study. AB - Various anthropometric measures, including height, have been associated with atrial fibrillation (AF). This raises questions about the appropriateness of using ratio measures such as body mass index (BMI), which contains height squared in its denominator, in the evaluation of AF risk. Among older adults, the optimal anthropometric approach to risk stratification of AF remains uncertain. Anthropometric and bioelectrical impedance measures were obtained from 4,276 participants (mean age = 72.4 years) free of cardiovascular disease in the Cardiovascular Health Study. During follow-up (1989-2008), 1,050 cases of AF occurred. BMI showed a U-shaped association, whereas height, weight, waist circumference, hip circumference, fat mass, and fat-free mass were linearly related to incident AF. The strongest adjusted association occurred for height (per each 1-standard-deviation increment, hazard ratio = 1.38, 95% confidence interval: 1.25, 1.51), which exceeded all other measures, including weight (hazard ratio = 1.21, 95% confidence interval: 1.13, 1.29). Combined assessment of log-transformed weight and height showed regression coefficients that departed from the 1 to -2 ratio inherent in BMI, indicating a loss of predictive information. Risk estimates for AF tended to be stronger for hip circumference than for waist circumference and for fat-free mass than for fat mass, which was explained largely by height. These findings highlight the prominent role of body size and the inadequacy of BMI as determinants of AF in older adults. PMID- 27188938 TI - Physical Frailty Assessment in Older Women: Can Simplification Be Achieved Without Loss of Syndrome Measurement Validity? AB - Different phenotypes have increasingly been used as tools for clinical characterization of frailty among older adults. Although there have been studies about the comparability and effectiveness of various simplifications and approximations of existing frailty phenotypes for risk prediction, there have been no studies in which investigators evaluated the stability of the clinical characterization achieved. In the present study, we used baseline (1992-1996) data from 786 community-dwelling women who were 70-79 years of age in the Women's Health and Aging Study I and II to compare physical frailty phenotypes (PFPs). Using the 5 criteria set forth by Fried, we created 15 PFPs that were positive for various combinations of 3 or 4 of those criteria and compared them with the PFP that included all 5 criteria in order to assess construct validity with regard to frailty syndrome characterization and predictive validity for adverse outcomes of aging. All PFPs exhibited high specificity and negative predictive values for identifying frailty syndrome. Three-item PFPs were insensitive but were the best performers for positive predictive value, with the highest positive predictive value of 0.86 seen in the PFP characterized by the combination of weakness, exhaustion, and weight loss. In comparison, the 5-criterion PFP achieved a sensitivity of 0.82 but a positive predictive value of only 0.53. With regard to predictive validity, it was not merely the number of criteria used to characterize the PFPs but rather the specific criteria combinations that predicted the risk of adverse outcomes. Our findings show that there clinically important contexts in which simplified PFPs cannot be used interchangeably. PMID- 27188939 TI - Bayesian Correction of Misclassification of Pertussis in Vaccine Effectiveness Studies: How Much Does Underreporting Matter? AB - Diagnosis of pertussis remains a challenge, and consequently research on the risk of disease might be biased because of misclassification. We quantified this misclassification and corrected for it in a case-control study of children in Philadelphia, Pennsylvania, who were 3 months to 6 years of age and diagnosed with pertussis between 2011 and 2013. Vaccine effectiveness (VE; calculated as (1 - odds ratio) * 100) was used to describe the average reduction in reported pertussis incidence resulting from persons being up to date on pertussis-antigen containing vaccines. Bayesian techniques were used to correct for purported nondifferential misclassification by reclassifying the cases per the 2014 Council of State and Territorial Epidemiologists pertussis case definition. Naive VE was 50% (95% confidence interval: 16%, 69%). After correcting for misclassification, VE ranged from 57% (95% credible interval: 30, 73) to 82% (95% credible interval: 43, 95), depending on the amount of underreporting of pertussis that was assumed to have occurred in the study period. Meaningful misclassification was observed in terms of false negatives detected after the incorporation of infant apnea to the 2014 case definition. Although specificity was nearly perfect, sensitivity of the case definition varied from 90% to 20%, depending on the assumption about missed cases. Knowing the degree of the underreporting is essential to the accurate evaluation of VE. PMID- 27188940 TI - Body Mass Index and Risk of Infections Among Women in the Danish National Birth Cohort. AB - We investigated the possible association between body mass index (BMI; weight (kg)/height (m)(2)) and hospitalization or treatment for acute infection in a prospective cohort study. We linked 75,001 women enrolled in the Danish National Birth Cohort from 1996 to 2002, who had information on BMI and a broad range of confounders, to data on infectious diseases and use of antimicrobial agents from the National Patient Register and the Danish Prescription Register. Associations were tested using Cox proportional hazards models. During 12 years of follow-up, we observed a U-shaped association between baseline BMI and later hospitalization for 1) any infectious disease and 2) infections of the respiratory tract, whereas a dose-response relationship was seen for skin infections. The most pronounced associations were seen for acute upper respiratory infections at multiple and unspecified sites (underweight (BMI <18.5): hazard ratio (HR) = 4.26, 95% confidence interval (CI): 1.69, 10.7; obesity (BMI >=30): HR = 3.64, 95% CI: 1.62, 8.18), erysipelas (obesity: HR = 5.19, 95% CI: 3.38, 7.95), and fungal infections (underweight: HR = 3.19, 95% CI: 1.53, 6.66). Slightly greater use of antimicrobials was observed among overweight (BMI 25-<30; HR = 1.08, 95% CI: 1.06, 1.10) and obese (HR = 1.21, 95% CI: 1.17, 1.24) women. Among Danish women, underweight and obesity were associated with increased risk of community-acquired infectious diseases, especially infections of the upper respiratory tract and skin. PMID- 27188941 TI - Exposure to Ambient Air Pollution and Premature Rupture of Membranes. AB - Premature rupture of membranes (PROM) is a major factor that predisposes women to preterm delivery. Results from previous studies have suggested that there are associations between exposure to air pollution and preterm birth, but evidence of a relationship with PROM is sparse. Modified Community Multiscale Air Quality models were used to estimate mean exposures to particulate matter less than 10 um or less than 2.5 um in aerodynamic diameter, nitrogen oxides, carbon monoxide, sulfur dioxide, and ozone among 223,375 singleton deliveries in the Air Quality and Reproductive Health Study (2002-2008). We used log-linear models with generalized estimating equations to estimate adjusted relative risks and 95% confidence intervals for PROM per each interquartile-range increase in pollutants across the whole pregnancy, on the day of delivery, and 5 hours before delivery. Whole-pregnancy exposures to carbon monoxide and sulfur dioxide were associated with an increased risk of PROM (for carbon monoxide, relative risk (RR) = 1.09, 95% confidence interval (CI): 1.04, 1.14; for sulfur dioxide, RR = 1.15, 95% CI: 1.06, 1.25) but not preterm PROM. Ozone exposure increased the risk of PROM on the day of delivery (RR = 1.06, 95% CI: 1.02, 1.09) and 1 day prior (RR = 1.04, 95% CI: 1.01, 1.07). In the 5 hours preceding delivery, there were 3%-7% increases in risk associated with exposure to ozone and particulate matter less than 2.5 um in aerodynamic diameter and inverse associations with exposure to carbon monoxide and nitrogen oxides. Acute and long-term air pollutant exposures merit further study in relation to PROM. PMID- 27188942 TI - Acquired Color Vision Defects and Hexane Exposure: A Study of San Francisco Bay Area Automotive Mechanics. AB - Occupational exposure to solvents, including n-hexane, has been associated with acquired color vision defects. Blue-yellow defects are most common and may be due to neurotoxicity or retinal damage. Acetone may potentiate the neurotoxicity of n hexane. We present results on nonhexane solvent and hexane exposure and color vision from a cross-sectional study of 835 automotive repair workers in the San Francisco Bay Area, California (2007-2013). Cumulative exposure was estimated from self-reported work history, and color vision was assessed using the Lanthony desaturated D-15 panel test. Log-binomial regression was used to estimate prevalence ratios for color vision defects. Acquired color vision defects were present in 29% of participants, of which 70% were blue-yellow. Elevated prevalence ratios were found for nonhexane solvent exposure, with a maximum of 1.31 (95% confidence interval (CI): 0.86, 2.00) for blue-yellow. Among participants aged <=50 years, the prevalence ratio for blue-yellow defects was 2.17 (95% CI: 1.03, 4.56) in the highest quartile of nonhexane solvent exposure and 1.62 (95% CI: 0.97, 2.72) in the highest category of exposure to hexane with acetone coexposure. Cumulative exposures to hexane and nonhexane solvents in the highest exposure categories were associated with elevated prevalence ratios for color vision defects in younger participants. PMID- 27188943 TI - Reevaluating Cumulative HIV-1 Viral Load as a Prognostic Predictor: Predicting Opportunistic Infection Incidence and Mortality in a Ugandan Cohort. AB - Recent studies have evaluated cumulative human immunodeficiency virus type 1 (HIV 1) viral load (cVL) for predicting disease outcomes, with discrepant results. We reviewed the disparate methodological approaches taken and evaluated the prognostic utility of cVL in a resource-limited setting. Using data on the Infectious Diseases Institute (Makerere University, Kampala, Uganda) cohort, who initiated antiretroviral therapy in 2004-2005 and were followed up for 9 years, we calculated patients' time-updated cVL by summing the area under their viral load curves on either a linear scale (cVL1) or a logarithmic scale (cVL2). Using Cox proportional hazards models, we evaluated both metrics as predictors of incident opportunistic infections and mortality. Among 489 patients analyzed, neither cVL measure was a statistically significant predictor of opportunistic infection risk. In contrast, cVL2 (but not cVL1) was a statistically significant predictor of mortality, with each log10 increase corresponding to a 1.63-fold (95% confidence interval: 1.02, 2.60) elevation in mortality risk when cVL2 was accumulated from baseline. However, whether cVL is predictive or not hinges on difficult choices surrounding the cVL metric and statistical model employed. Previous studies may have suffered from confounding bias due to their focus on cVL1, which strongly correlates with other variables. Further methodological development is needed to illuminate whether the inconsistent predictive utility of cVL arises from causal relationships or from statistical artifacts. PMID- 27188944 TI - Association of Clomiphene and Assisted Reproductive Technologies With the Risk of Neural Tube Defects. AB - Clomiphene and assisted reproductive technologies (ART) are methods used to help subfertile couples become pregnant. ART has been reported to be associated with neural tube defects (NTDs) in offspring. To evaluate these associations, we studied mothers of 219 cases and 4,262 controls from the Slone Epidemiology Center Birth Defects Study (1993-2012) who were interviewed within 6 months after delivery about pregnancy events, including use of fertility treatments. We considered exposures to clomiphene (without ART) and ART during the periconceptional period. Logistic regression models were used to calculate adjusted odds ratios and 95% confidence intervals, controlling for education and study center. We observed elevated adjusted odds ratios of 2.1 (95% confidence interval: 0.9, 4.8) and 2.0 (95% confidence interval: 1.1, 3.6) for clomiphene and ART exposure, respectively. We performed a mediation analysis to assess whether the observed elevated NTD risk was mediated through multiple births. For clomiphene exposure without ART use, the direct effect estimate of the adjusted odds ratio (aORDE) was 1.7 and the indirect effect estimate (aORIE) was 1.4. Conversely, for ART exposure, the aORDE was 0.9 and the aORIE was 2.5. Our findings suggest that relatively little of the clomiphene-NTD association is mediated through the pathway of multiple births, while the ART-NTD association was explained by the multiple-births pathway. PMID- 27188947 TI - Re: "Premenstrual Syndrome and Subsequent Risk of Hypertension in a Prospective Study". PMID- 27188946 TI - Neighborhood Environments and Incident Hypertension in the Multi-Ethnic Study of Atherosclerosis. AB - We examined relationships between neighborhood physical and social environments and incidence of hypertension in a cohort of 3,382 adults at 6 sites in the United States over 10 years of follow-up (2000-2011), using data from the Multi Ethnic Study of Atherosclerosis. The sample was aged 45-84 years (mean = 59 years) and free of clinical cardiovascular disease and hypertension at baseline. Of the participants, 51% were female, 44% white, 23% Hispanic, 21% black, and 13% Chinese-American; 39% of participants developed hypertension during an average of 7.2 years of follow-up. Cox models were used to estimate associations of time varying cumulative average neighborhood features (survey-based healthy food availability, walking environment, social cohesion, safety, and geographic information system-based density of favorable food stores and recreational resources) with incident hypertension. After adjustment for individual and neighborhood-level covariates, a 1-standard-deviation increase in healthy food availability was associated with a 12% lower rate of hypertension (hazard ratio = 0.88, 95% confidence interval: 0.82, 0.95). Other neighborhood features were not related to incidence of hypertension. The neighborhood food environment is related to the risk of hypertension. PMID- 27188945 TI - Herpes Simplex Virus Type 2 Seroprevalence and Ultrasound-Diagnosed Uterine Fibroids in a Large Population of Young African-American Women. AB - For decades reproductive tract infections (RTIs) have been hypothesized to play a role in uterine fibroid development. The few previous studies conducted used self reported history of RTIs and had inconsistent findings. We investigated this hypothesis further using serological analysis, an immunological measure of past exposure. We focused on herpes simplex virus type 2 (HSV-2) because prior published data have suggested a possible association with fibroids, and serology for HSV-2 is much more sensitive than self-report. We used cross-sectional enrollment data from African-American women enrolled in a prospective study of fibroid incidence and growth (recruited 2010-2012) in the Detroit, Michigan, area. The women were aged 23-34 years and were screened for fibroids using a standardized ultrasound examination at their enrollment. Age- and multivariable adjusted logistic regression models were used to estimate odds ratios. Of 1,696 participants, 1,658 had blood samples and HSV-2 serology results; 22% of participants with serology results had fibroids. There was no significant association between HSV-2 seropositivity and the presence of fibroids (multivariable-adjusted odds ratio = 0.94, 95% confidence interval: 0.73, 1.20), nor were there any associations with size of the largest fibroid, number of fibroids, or total fibroid volume. Our data provide no evidence for an influence of HSV-2 exposure on fibroid risk in young African-American women. Further study of other serologically measured RTIs is warranted. PMID- 27188948 TI - Changes in Susceptibility to Heat During the Summer: A Multicountry Analysis. AB - Few studies have examined the variation in mortality risk associated with heat during the summer. Here, we apply flexible statistical models to investigate the issue by using a large multicountry data set. We collected daily time-series data of temperature and mortality from 305 locations in 9 countries, in the period 1985-2012. We first estimated the heat-mortality relationship in each location with time-varying distributed lag non-linear models, using a bivariate spline to model the exposure-lag-response over lag 0-10. Estimates were then pooled by country through multivariate meta-analysis. Results provide strong evidence of a reduction in risk over the season. Relative risks for the 99th percentile versus the minimum mortality temperature were in the range of 1.15-2.03 in early summer. In late summer, the excess was substantially reduced or abated, with relative risks in the range of 0.97-1.41 and indications of wider comfort ranges and higher minimum mortality temperatures. The attenuation is mainly due to shorter lag periods in late summer. In conclusion, this multicountry analysis suggests a reduction of heat-related mortality risk over the summer, which can be attributed to several factors, such as true acclimatization, adaptive behaviors, or harvesting effects. These findings may have implications on public health policies and climate change health impact projections. PMID- 27188949 TI - Relating Pneumococcal Carriage Among Children to Disease Rates Among Adults Before and After the Introduction of Conjugate Vaccines. AB - The use of pneumococcal conjugate vaccines (PCVs) in children has a strong indirect effect on disease rates in adults. When children are vaccinated with PCVs, other serotypes that are not targeted by the vaccine can increase in frequency (serotype replacement) and reduce the direct and indirect benefits of the vaccine. To understand and predict the likely impacts of serotype replacement, it is important to know how patterns in the transmission of serotypes among children relate to disease rates in adults. We used data on pneumococcal carriage and disease from Navajo Nation children and adults collected before and after the routine use of PCVs (1998-2012). Using regression models within a Bayesian framework, we found that serotype-specific carriage and invasiveness (disease incidence divided by carriage prevalence) had similar patterns in children and adults. Moreover, carriage in children, invasiveness in children, and a serotype-specific random intercept (which captured additional variation associated with the serotypes) could predict the incidence serotype specific pneumococcal disease in adults 18-39 years of age and those 40 years of age or older in the era of routine use of PCVs. These models could help us predict the effects of future pneumococcal vaccine use in children on disease rates in adults, and the modeling approach developed here could be used to test these findings in other settings. PMID- 27188950 TI - What Transmission Precautions Best Control Influenza Spread in a Hospital? AB - Influenza is a significant problem within hospitals, leading to extended hospital stays, excess morbidity and mortality, and economic loss. Prevention and control strategies are generally "bundled"; therefore, the individual effects of particular strategies and the value of combined strategies cannot be determined directly, making it difficult to discern the optimal strategy. To quantify the individual and joint effectiveness of several known influenza infection control measures used in general hospitals, we simulated influenza transmission at a hypothetical hospital in Ann Arbor, Michigan, during a 1-year seasonal epidemic (June 2012-June 2013), using a susceptible-exposed-infected-recovered (SEIR) compartmental model. The hospital population comprised patients and health-care workers, interacting with its larger community population. Parameter ranges and values were determined from the literature (both national and local to Ann Arbor) and took into account coverage levels and effects of vaccination. The most effective individual strategies, based on percent reduction of cases, were: hand washing (11%-27%), health-care worker vaccination (6%-19%), prevaccination of patients (4%-17%), patient isolation (5%-16%), antiviral treatment (4%-14%), and use of face masks (3%-10%). Use of all strategies together with ideal levels of compliance could potentially halve the number of observed hospital cases of influenza; under a more realistic scenario, an almost 40% reduction could be achieved. A multifaceted approach is imperative to control and prevent nosocomial influenza in health-care settings. PMID- 27188952 TI - Trends in the Incidence of Parkinson Disease in the General Population: The Rotterdam Study. AB - We investigated trends in the incidence of parkinsonism and Parkinson disease (PD) by comparing data from the first 2 subcohorts of the Rotterdam Study, a prospective, population-based cohort study (first subcohort: baseline 1990 with 10 years of follow-up; second subcohort, baseline 2000 with 10 years of follow up). From the baseline years, we observed differences in the second subcohort that were associated with a lower risk of PD for some but not all baseline risk factors. Participants in both subcohorts were followed for a maximum of 10 years and monitored for the onset of parkinsonism, the onset of dementia, or death, until January 1, 2011. We used Poisson regression models to compare the incidences of parkinsonism, both overall and by cause (PD and secondary causes), and competitive events (incident dementia and death) as well as the mortality of parkinsonism patients in the 2 subcohorts. In the 1990 subcohort, there were 182 cases of parkinsonism (84 of which were PD) during 57,052 person-years. In the 2000 subcohort, we observed 28 cases of parkinsonism (10 with PD) during 22,307 person-years. The overall age- and sex-adjusted incidence of parkinsonism was lower in the 2000 subcohort (incidence rate ratio = 0.55, 95% confidence interval: 0.36, 0.81), and PD incidence declined sharply (incidence rate ratio = 0.39, 95% confidence interval: 0.19, 0.72). Competitive event rates were lower in the 2000 subcohort, and mortality rates among persons with parkinsonism remained stable. These findings suggest that the incidence of parkinsonism in general, and of PD in particular, decreased between 1990 and 2011. PMID- 27188951 TI - Cost-Effectiveness of Pertussis Vaccination During Pregnancy in the United States. AB - Vaccination against pertussis has reduced the disease burden dramatically, but the most severe cases and almost all fatalities occur in infants too young to be vaccinated. Recent epidemiologic evidence suggests that targeted vaccination of mothers during pregnancy can reduce pertussis incidence in their infants. To evaluate the cost-effectiveness of antepartum maternal vaccination in the United States, we created an age-stratified transmission model, incorporating empirical data on US contact patterns and explicitly modeling parent-infant exposure. Antepartum maternal vaccination incurs costs of $114,000 (95% prediction interval: 82,000, 183,000) per quality-adjusted life-year, in comparison with the strategy of no adult vaccination, and is cost-effective in the United States according to World Health Organization criteria. By contrast, vaccinating a second parent is not cost-effective, and vaccination of either parent postpartum is strongly dominated by antepartum maternal vaccination. Nonetheless, postpartum vaccination of mothers who were not vaccinated antepartum improves upon the current recommendation of untargeted adult vaccination. Additionally, the temporary direct protection of the infant due to maternal antibody transfer has efficacy for infants comparable to that conferred to toddlers by the full primary vaccination series. Efficient protection against pertussis for infants begins before birth. We highly recommend antepartum vaccination for as many US mothers as possible. PMID- 27188954 TI - Efficient visible light photocatalytic NOx removal with cationic Ag clusters grafted (BiO)2CO3 hierarchical superstructures. AB - A facile method was developed to graft cationic Ag clusters on (BiO)2CO3 hierarchical superstructures (BHS) surface to improve their visible light activity. Significantly, the resultant Ag clusters-grafted BHS displayed a highly enhanced visible light photocatalytic performance for NOx removal due to the direct interfacial charge transfer (IFCT) from BHS to Ag clusters. The chemical and coordination state of the cationic Ag clusters was determined with the extended X-ray absorption fine structure (EXAFS) and a theoretical structure model was proposed for this unique Ag clusters. The charge transfer process and the dominant reactive species (OH) were revealed on the basis of electron spin resonance (ESR) trapping. A new photocatalysis mechanism of Ag clusters-grafted BHS under visible light involving IFCT process was uncovered. In addition, the cationic Ag clusters-grafted BHS also demonstrated high photochemical and structural stability under repeated photocatalysis runs. The perspective of enhancing photocatalysis through combination of microstructural optimization and IFCT could provide a new avenue for the developing efficient visible light photocatalysts. PMID- 27188955 TI - Clinical Abstracts of the British Small Animal Veterinary Association Congress 2016, Birmingham, UK, April 7-10, 2016. PMID- 27188953 TI - Applying Multiple Methods to Comprehensively Evaluate a Patient Portal's Effectiveness to Convey Information to Patients. AB - BACKGROUND: Patient portals have yet to achieve their full potential for enhancing health communication and improving health outcomes. Although the Patient Protection and Affordable Care Act in the United States mandates the utilization of patient portals, and usage continues to rise, their impact has not been as profound as anticipated. OBJECTIVE: The objective of our case study was to evaluate how well portals convey information to patients. To demonstrate how multiple methodologies could be used to evaluate and improve the design of patient-centered portals, we conducted an in-depth evaluation of an exemplar patient-centered portal designed to promote preventive care to consumers. METHODS: We used 31 critical incident patient interviews, 2 clinician focus groups, and a thematic content analysis to understand patients' and clinicians' perspectives, as well as theoretical understandings of the portal's use. RESULTS: We gathered over 140 critical incidents, 71.8% (102/142) negative and 28.2% (40/142) positive. Positive incident categories were (1) instant medical information access, (2) clear health information, and (3) patient vigilance. Negative incident categories were (1) standardized content, (2) desire for direct communication, (3) website functionality, and (4) difficulty interpreting laboratory data. Thematic analysis of the portal's immediacy resulted in high scores in the attributes enhances understanding (18/23, 78%), personalization (18/24, 75%), and motivates behavior (17/24, 71%), but low levels of interactivity (7/24, 29%) and engagement (2/24, 8%). Two overarching themes emerged to guide portal refinements: (1) communication can be improved with directness and interactivity and (2) perceived personalization must be greater to engage patients. CONCLUSIONS: Results suggest that simple modifications, such as increased interactivity and personalized messages, can make portals customized, robust, easily accessible, and trusted information sources. PMID- 27188956 TI - Computational approach to analyze isolated ssDNA aptamers against angiotensin II. AB - Aptamers are oligonucleotides with highly structured molecules that can bind to their targets through specific 3-D conformation. Commonly, not all the nucleotides such as primer binding fixed region and some other sequences are vital for aptamers folding and interaction. Elimination of unnecessary regions needs trustworthy prediction tools to reduce experimental efforts and errors. Here we introduced a manipulated in-silico approach to predict the 3-D structure of aptamers and their target interactions. To design an approach for computational analysis of isolated ssDNA aptamers (FLC112, FLC125 and their truncated core region including CRC112 and CRC125), their secondary and tertiary structures were modeled by Mfold and RNA composer respectively. Output PDB files were modified from RNA to DNA in the discovery studio visualizer software. Using ZDOCK server, the aptamer-target interactions were predicted. Finally, the interaction scores were compared with the experimental results. In-silico interaction scores and the experimental outcomes were in the same descending arrangement of FLC112>CRC125>CRC112>FLC125 with similar intensity. The consistent results of innovative in-silico method with experimental outputs, affirmed that the present method may be a reliable approach. Also, it showed that the exact in silico predictions can be utilized as a credible reference to find aptameric fragments binding potency. PMID- 27188957 TI - Stable and enhanced gene expression in Clostridium acetobutylicum using synthetic untranslated regions with a stem-loop. AB - Gene overexpression is one of the most basic strategies in metabolic engineering, but the factors determining gene expression levels have been poorly studied in Clostridium species. In this study, we found that a short single-stranded 5' untranslated region (UTR) sequence led to decreased gene expression in Clostridium acetobutylicum. Using an in vitro enzyme assay and reverse transcription-quantitative PCR, we found that addition of a small stem-loop at the 5' end of mRNA increased mRNA levels and thereby protein expression levels up to 4.6-fold, possibly protecting mRNA from exonuclease attack. Gene-expression levels were apparently independent of the stability of the added stem-loop; the existence of a stem-loop itself appears to be more important. Our results indicate that efficient expression cassettes can be designed by taking the 5' UTR into consideration, as the expression levels can vary even though the same promoter and RBS are used. These findings will be useful for developing a more reliable gene expression system for metabolic engineering of Clostridium strains. PMID- 27188958 TI - Chronological clinical and pathological documentation of porcine ulcerative dermatitis. AB - BACKGROUND: Porcine ulcerative dermatitis syndrome (PUDS) is a rare disease of breeding sows with an unknown pathogenesis. OBJECTIVE: To describe the evolution of clinical and histopathological lesions over the course of the disease and to elucidate the pathogenesis. ANIMAL: A 24-month-old, pluriparous, large white sow presented during gestation with ulcerations around the teats compatible with PUDS. METHODS AND RESULTS: Clinical and histopathological lesions were monitored over the course of the disease (i.e. during and after the subsequent pregnancy). A clear gestation-dependent flare of the lesions was observed with partial resolution occurring postpartum. The histological pattern presented as a lymphocytic interface dermatitis. CONCLUSIONS AND CLINICAL IMPORTANCE: The findings in this case report link gestation with the development of clinical signs and histological changes. Multiparity appears to enhance severity and may finally result in a self-perpetuating disease. Therefore, it seems advisable to cull breeding sows after they have developed PUDS. PMID- 27188959 TI - Glycans affect DNA extraction and induce substantial differences in gut metagenomic studies. AB - Exopolysaccharides produced by bacterial species and present in feces are extremely inhibitory to DNA restriction and can cause discrepancies in metagenomic studies. We determined the effects of different DNA extraction methods on the apparent composition of the gut microbiota using Illumina MiSeq deep sequencing technology. DNA was extracted from the stool from an obese female using 10 different methods and the choice of DNA extraction method affected the proportional abundance at the phylum level, species richness (Chao index, 227 to 2,714) and diversity (non parametric Shannon, 1.37 to 4.4). Moreover DNA was extracted from stools obtained from 83 different individuals by the fastest extraction assay and by an extraction assay that degradated exopolysaccharides. The fastest extraction method was able to detect 68% to 100% genera and 42% to 95% species whereas the glycan degradation extraction method was able to detect 56% to 93% genera and 25% to 87% species. To allow a good liberation of DNA from exopolysaccharides commonly presented in stools, we recommend the mechanical lysis of stools plus glycan degradation, used here for the first time. Caution must be taken in the interpretation of current metagenomic studies, as the efficiency of DNA extraction varies widely among stool samples. PMID- 27188961 TI - Cortical astrogliosis and increased perivascular aquaporin-4 in idiopathic intracranial hypertension. AB - The syndrome idiopathic intracranial hypertension (IIH) includes symptoms and signs of raised intracranial pressure (ICP) and impaired vision, usually in overweight persons. The pathogenesis is unknown. In the present prospective observational study, we characterized the histopathological changes in biopsies from the frontal brain cortical parenchyma obtained from 18 IIH patients. Reference specimens were sampled from 13 patients who underwent brain surgery for epilepsy, tumors or acute vascular diseases. Overnight ICP monitoring revealed abnormal intracranial pressure wave amplitudes in 14/18 IIH patients, who underwent shunt surgery and all responded favorably. A remarkable histopathological observation in IIH patients was patchy astrogliosis defined as clusters of hypertrophic astrocytes enclosing a nest of nerve cells. Distinct astrocyte domains (i.e. no overlap between astrocyte processes) were lacking in most IIH biopsy specimens, in contrast to their prevalence in reference specimens. Evidence of astrogliosis in IIH was accompanied with significantly increased aquaporin-4 (AQP4) immunoreactivity over perivascular astrocytic endfeet, compared to the reference specimens, measured with densitometry. Scattered CD68 immunoreactive cells (activated microglia and macrophages) were recognized, indicative of some inflammation. No apoptotic cells were demonstrable. We conclude that the patchy astrogliosis is a major finding in patients with IIH. We propose that the astrogliosis impairs intracranial pressure volume reserve capacity, i.e. intracranial compliance, and contributes to the IIH by restricting the outflow of fluid from the cranium. The increased perivascular AQP4 in IIH may represent a compensatory mechanism to enhance brain fluid drainage. PMID- 27188962 TI - Witnesses of causal nonseparability: an introduction and a few case studies. AB - It was recently realised that quantum theory allows for so-called causally nonseparable processes, which are incompatible with any definite causal order. This was first suggested on a rather abstract level by the formalism of process matrices, an extension of the quantum formalism which only assumes that quantum theory holds locally in some observers' laboratories, but does not impose a global causal structure; it was then shown, on a more practical level, that the quantum switch-a new, already implementable resource for quantum computation that goes beyond causally ordered circuits-provided precisely a physical example of a causally nonseparable process. To demonstrate that a given process is causally nonseparable, the concept of witnesses of causal nonseparability was introduced. Here we present a shorter introduction to this concept, and concentrate on some explicit examples-by considering in particular different noise models for the quantum switch-to show how to construct and use such witnesses in practice. PMID- 27188960 TI - On-treatment HCV RNA as a predictor of sustained virological response in HCV genotype 3-infected patients treated with daclatasvir and sofosbuvir. AB - BACKGROUND AND AIMS: Many currently available direct-acting antiviral (DAA) regimens are less effective against HCV genotype 3 than against other HCV genotypes. The all-oral, pangenotypic DAA combination of daclatasvir (NS5A inhibitor) + sofosbuvir (nucleotide NS5B inhibitor) was studied in genotype 3 infected treatment-naive and -experienced patients (ALLY-3) who achieved rates of sustained virological response at post-treatment Week 12 (SVR12) of 90 and 86% respectively. In this analysis, we assessed whether on-treatment responses to daclatasvir + sofosbuvir in genotype 3-infected patients could predict treatment outcome. METHODS: In ALLY-3, treatment-naive and -experienced patients, with or without cirrhosis, were treated with daclatasvir + sofosbuvir for 12 weeks. HCV RNA kinetics and categorical virological responses on treatment were assessed. The proportions of responders and nonresponders by study week, and time to first undetectable HCV RNA, were analysed for utility in predicting treatment outcome. RESULTS: Overall, HCV RNA levels declined rapidly during Week 1 of treatment in both treatment-naive and -experienced cohorts. Although patients with cirrhosis had a slower initial virological response as measured by the proportion of patients with HCV RNA below the lower limit of quantification at Week 1, responses converged thereafter. Positive and negative predictive values calculated for on-treatment responses were generally comparable with the overall SVR12 rate and were therefore limited indicators of outcome. SVR12 rates were not impacted by time to first undetectable HCV RNA. CONCLUSIONS: On-treatment responses are not useful predictors of ultimate virological response to the daclatasvir + sofosbuvir regimen. PMID- 27188963 TI - Escherichia coli bacteraemias in intensive care unit patients. AB - BACKGROUND: Although bacterial infections are common in critically ill patients, isolation of bacteria from the sample is not always unambiguous. The authors addressed Escherichia coli bacteraemia in patients treated in the Intensive Care Unit in the Teaching Hospital in Gdansk in 2002-2009. METHODS: Using a computer database, the names of Escherichia coli positive patients and dates of blood sampling were found, followed by a retrospective assessment whether positive blood cultures were accompanied by the clinical features of sepsis or asymptomatic bacteraemia. RESULTS: Positive cultures were found in 40 blood samples (36 patients). Bacteraemia was diagnosed in 11, sepsis in 10, severe sepsis in 6 and septic shock in 13 cases. In the bacteraemia group, the condition originated from the gastrointestinal tract - 4 cases; from the lungs - 1; while in 6 cases, the aetiology was not detected. In patients with an infection, the likely source was the gastrointestinal tract - 12 cases; the lungs - 4; and pyothorax - 2. In 11 cases, the aetiology remained unidentified. In 3 patients in the bacteraemia group, cultures of other microorganisms were found to be positive, while there were 4 cases among the septic patients. In the bacteraemia group, 8 patients died in the intensive care unit, without relation to bacteraemia. Amongst septic patients 17 died, including 12 whose death was probably attributable to Escherichia coli infection. CONCLUSIONS: Escherichia coli bacteraemias and infections have been and will remain an everyday problem in hospital wards. The differentiation of asymptomatic bacteraemia from infection is essential for rational antibiotic therapy, which is particularly important considering the increasing resistance of microorganisms. PMID- 27188964 TI - Efficiency of goal-directed oxygen delivery in ICU patients. AB - BACKGROUND: Current clinical practice guidelines promote a goal-directed approach for oxygen delivery with respect to SpO2 objectives. We evaluated the efficiency of a strategy based on goal-directed O2 delivery in the ICU. METHODS: A group of 30 patients (Group 1) with a proven history of chronic obstructive pulmonary disease suffering from acute hypercarbic exacerbation was compared to 2 other groups of patients admitted for acute respiratory failure with no history of pulmonary disease: 30 patients requiring oxygen supply and/or non-invasive ventilation (Group 2) and 30 requiring invasive ventilation (Group 3). The delivery of oxygen was based on SpO2 measurement: 88-94% for Group 1 and 90-96% for others. The time spent with an SpO2 below, within and above the prescribed limits was collected. RESULTS: The mean time spent within the prescribed range was for Groups 1, 2 and 3, respectively as follows: 61.9% [60.5-63.2], 63.7% [62.3-65] and 56.4% [55.3-57.6] (P < 0.001 for each group). A history of chronic obstructive pulmonary disease was not correlated with better results (P = 0.11), while invasive ventilation was related to the time spent out of the prescribed range (P < 0.001; OR 1.3 [1.22-1.28]) especially in hyperoxaemia (40.7% [39.6 41.8] P < 0.001). Efficiency seems unrelated to nursing workload or night team exhaustion (r = -0.09, P = 0.77). CONCLUSIONS: Goal-directed oxygen delivery based on SpO2 objectives in ICU patients ensures that in only approximately 64% of the time, SpO2 stays within the prescribed range. PMID- 27188965 TI - Patent foramen ovale. AB - Patent foramen ovale (PFO) is the most common congenital heart abnormality of fetal origin and is present in approximately ~25% of the worldwide adult population. PFO is the consequence of failed closure of the foramen ovale, a normal structure that exists in the fetus to direct blood flow directly from the right to the left atrium, bypassing the pulmonary circulation. PFO has historically been associated with an increased risk of stroke, the mechanism of which has been attributed to the paradoxical embolism of venous thrombi that shunt through the PFO directly to the left atrium. However, several studies have failed to show an increased risk of stroke in asymptomatic patients with a PFO, and the risk of stroke recurrence is low in patients who have had a stroke that may be attributed to a PFO. With the advent of transoesophageal and transthoracic echocardiography, as well as transcranial Doppler, a PFO can be routinely detected in clinical practice. Medical treatment with either antiplatelet or anticoagulation therapy is recommended. At the current time, closure of the PFO by percutaneous interventional techniques does not appear to reduce the risk of stroke compared to conventional medical treatment, as shown by three large clinical trials. Considerable controversy remains regarding the optimal treatment strategy for patients with both cryptogenic stroke and PFO. This Primer discusses the epidemiology, mechanisms, pathophysiology, diagnosis, screening, management and effects on quality of life of PFO. PMID- 27188966 TI - Good concordance between patients and their non-professional carers about factors associated with a 'good death' and other important end-of-life decisions. AB - OBJECTIVES: The aim of this study was to investigate concordance between patients and non-professional carers about factors associated with a 'good death' and other end-of-life decisions. METHODS: Patients completed a questionnaire about end-of-life care issues, and were asked to rank the importance of factors linked to a 'good death'. Carers also completed a questionnaire about end-of-life care issues relating to the patient, and whether or not they agreed with those choices (ie, medical treatments, PPD). Carers were also asked to rank the importance of factors linked to a 'good death' to the patient, and to them personally at that point in time. RESULTS: Only 69% of patients stated they had discussed their preferences for end-of-life care with their respective carer. The rankings were similar for the patient and the carer's views of what was important for the patient, although the patients ranked 'to be involved in decisions about my care' as less important than the carers, while the carers ranked 'to have sorted out my personal affairs' as less important than the patients. CONCLUSIONS: When discussions around end-of-life choices do occur, carers generally appear to agree with the patients' preferences around end-of-life treatment, and preferred place of death. PMID- 27188967 TI - The predictive value of fall assessment tools for patients admitted to hospice care. AB - OBJECTIVES: Fall assessment tools are commonly used to evaluate the likelihood of fall. For patients found to be at high risk, patient-specific fall prevention interventions are implemented. The purposes of this study were to describe the population, evaluate and compare the efficacy of fall assessment tools, and suggest the best use for these tools in hospice. METHODS: Data were downloaded from the electronic medical record for all patients who were admitted to and died in hospice care in 2013. Variables included demographic, clinical and initial fall assessment scores that had been computed on admission to hospice care, using our standard fall assessment tool. To facilitate comparison among three tools, additional fall assessment calculations were made for each patient using the Morse Fall Scale and MACH-10, two tools commonly used in a variety of healthcare settings. RESULTS: Data were available for 3446 hospice patients. Female patients were less likely to fall than males; Fallers lived longer than Nonfallers; and patients with a primary dementia diagnosis fell 10 days sooner than those with a primary non-dementia diagnosis. A comparison of three fall assessment tools revealed that no tool had a good positive predictive value, but each demonstrated a good negative predictive value. CONCLUSIONS: Fall assessment scores should not be used as the sole predictor of likelihood of fall, and are best used as a supplement to clinical judgement. Patients with a primary dementia diagnosis are likely to fall earlier in their hospice care than those with other primary diagnoses. PMID- 27188968 TI - Accuracy of Multiparametric Magnetic Resonance Imaging for Extracapsular Extension of Prostate Cancer in Community Practice. AB - INTRODUCTION: The presence of extracapsular extension (ECE) in prostate cancer (PCa) can influence a surgeon's decision to perform a nerve-sparing approach during radical prostatectomy (RP). Preoperatively, multiparametric MRI (mp-MRI) is often used to stage PCa. More recently, the use of mp-MRI has gained wide acceptance in fusion biopsy of the prostate. In this framework, the reported accuracy of mp-MRI has been highly variable, with data often originating from large referral centers with experienced radiologists. We sought to determine the sensitivity and specificity of mp-MRI for detecting ECE in the community. MATERIALS AND METHODS: We reviewed a prospectively maintained database of men with PCa who had undergone RP. We recorded the prevalence of ECE at RP and determined the sensitivity, specificity, positive predictive value, and negative predictive value of MRI for detecting ECE. We assessed these values according to the D'Amico risk groups and compared the predictive value of MRI to that of the Partin tables. RESULTS: The prevalence of ECE was 11.5%, 28.1%, and 47.1% in the low-, intermediate, and high-risk groups, respectively, with an overall prevalence of 24.1%. The overall sensitivity, specificity, positive predictive value, and negative predictive value of MRI was 12.5%, 93.1%, 36.4%, and 77.0%, respectively. CONCLUSION: The reduction in the sensitivity of preoperative mp-MRI to determine ECE in the community setting is significant. Even with stratification using the D'Amico criteria and Partin tables, the performance of mp-MRI was not significantly improved. Because most cases of PCa are diagnosed and treated in the community, it is questionable whether mp-MRI is a suitable staging modality in the community. PMID- 27188970 TI - Regeneration-Based Quantification of Coumarins (Scopoletin and Scoparone) in Abutilon indicum In Vitro Cultures. AB - Abutilon indicum exploited for its immense value has been propagated successfully through multiple shoot induction and somatic embryogenesis. Direct regeneration (8.20 +/- 0.83 shoots) was achieved from nodal explants using 0.5 mg/l kinetin (Kn) in MS media. The basal callus from nodal explants turned embryogenic on subsequent introduction of 0.2 mg/l TDZ into the Kn-supplemented media, giving rise to somatic embryos. The embryogenic potential of calli expressed in terms of embryo-forming capacity (EFC) increased from 8.15 EFC to 20.95 EFC after plasmolysis. The phytochemical analysis (HPLC) for the presence of scopoletin and scoparone has revealed a unique accumulation pattern, with higher levels of scopoletin during the earlier stages and scoparone in the later stages of development. The embryogenic calli contained the highest amount of coumarins (99.20 +/- 0.97 and 61.03 +/- 0.47 MUg/gFW, respectively) followed by regenerated plant (9.43 +/- 0.20 and 36.36 +/- 1.19 MUg/gFW, respectively), obtained via somatic embryogenesis. Rapid multiplication of A. indicum equipped with two potent coumarins is important in order to meet the commercial demand for combat against dreadful diseases, thereby providing a new platform for plant-based drugs and their manufacture on a commercial scale. PMID- 27188969 TI - TRPV1 is crucial for proinflammatory STAT3 signaling and thermoregulation associated pathways in the brain during inflammation. AB - Transient receptor potential vanilloid receptor 1 (TRPV1) is a non-selective cation channel that is stimulated by heat (>43 degrees C), mechanical/osmotic stimuli, and low pH. The importance of TRPV1 in inflammatory responses has been demonstrated, whereas its participation in brains remains unclear. In the present study, the intracerebroventricular (icv) administration of the TRPV1 agonist resiniferatoxin (RTX) induced the activation of signal transducer and activator of transcription 3 (STAT3) in circumventricular organs (CVOs) and thermoregulation-associated brain regions with a similar patttern to the peripheral and icv administration of lipopolysaccharide (LPS). With the peripheral and icv LPS stimuli, STAT3 activation was significantly lower in Trpv1(-/-) mice than in Trpv1(+/+) mice. The icv administration of RTX induced transient hypothermia, whereas that of the TRPV1 antagonist capsazepine enhanced the magnitude and period of LPS-induced hyperthermia. These results indicate that TRPV1 is important for activating proinflammatory STAT3 signaling and thermoregulation-associated brain pathways in the brain. PMID- 27188971 TI - Wet and Dry Forms of Bacterial Cellulose Synthetized by Different Strains of Gluconacetobacter xylinus as Carriers for Yeast Immobilization. AB - The present study aimed to explore and describe the properties of bacterial cellulose (BC) membranes obtained from three different strains of Gluconacetobacter xylinus for 72, 120, and 168 h, used as a carrier support for the immobilization of Saccharomyces cerevisiae. The experiments also included the analysis of glucose consumption and alcohol production during the fermentation process displayed by yeasts immobilized on the BC surface. The results of the present study demonstrate that the number of immobilized yeast cells is dependent on the type of cellulose-synthesizing strain, cellulose form, and duration of its synthesis. The BC in the form of wet membranes obtained after 3 days of synthesis displayed the most favorable properties as a carrier for yeast immobilization. The immobilization of yeast cells on BC, regardless of its form, increased the amount of the produced alcohol as compared to free cells. The yeast cells immobilized in BC were able to multiply on its surface during the fermentation process. PMID- 27188972 TI - Collagen-Immobilized Lipases Show Good Activity and Reusability for Butyl Butyrate Synthesis. AB - Candida rugosa lipases were immobilized onto collagen fibers through glutaraldehyde cross-linking method. The immobilization process has been optimized. Under the optimal immobilization conditions, the activity of the collagen-immobilized lipase reached 340 U/g. The activity was recovered of 28.3 % by immobilization. The operational stability of the obtained collagen-immobilized lipase for hydrolysis of olive oil emulsion was determined. The collagen immobilized lipase showed good tolerance to temperature and pH variations in comparison to free lipase. The collagen-immobilized lipase was also applied as biocatalyst for synthesis of butyl butyrate from butyric acid and 1-butanol in n hexane. The conversion yield was 94 % at the optimal conditions. Of its initial activity, 64 % was retained after 5 cycles for synthesizing butyl butyrate in n hexane. PMID- 27188973 TI - Screening and Characterization of Cold-Active beta-Galactosidase Producing Psychrotrophic Enterobacter ludwigii from the Sediments of Arctic Fjord. AB - Low-temperature-tolerant microorganisms and their cold-active enzymes could be an innovative and invaluable tool in various industrial applications. In the present study, bacterial isolates from the sediment samples of Kongsfjord, Norwegian Arctic, were screened for beta-galactosidase production. Among the isolates, KS25, KS85, KS60, and KS92 have shown good potential in beta-galactosidase production at 20 degrees C. 16SrRNA gene sequence analysis revealed the relatedness of the isolates to Enterobacter ludwigii. The optimum growth temperature of the isolate was 25 degrees C. The isolate exhibited good growth and enzyme production at a temperature range of 15-35 degrees C, pH 5-10. The isolate preferred yeast extract and lactose for the maximum growth and enzyme production at conditions of pH 7.0, temperature of 25 degrees C, and agitation speed of 100 rpm. The growth and enzyme production was stimulated by Mn2+ and Mg2+ and strongly inhibited by Zn2+, Ni2+, and Cu+. beta-Galactosidases with high specific activity at low temperatures are very beneficial in food industry to compensate the nutritional problem associated with lactose intolerance. The isolate exhibited a remarkable capability to utilize clarified whey, an industrial pollutant, for good biomass and enzyme yield and hence could be well employed in whey bioremediation. PMID- 27188974 TI - Liquid Crystalline Nanoparticles as an Ophthalmic Delivery System for Tetrandrine: Development, Characterization, and In Vitro and In Vivo Evaluation. AB - The purpose of this study was to develop novel liquid crystalline nanoparticles (LCNPs) that display improved pre-ocular residence time and ocular bioavailability and that can be used as an ophthalmic delivery system for tetrandrine (TET). The delivery system consisted of three primary components, including glyceryl monoolein, poloxamer 407, and water, and two secondary components, including Gelucire 44/14 and amphipathic octadecyl-quaternized carboxymethyl chitosan. The amount of TET, the amount of glyceryl monoolein, and the ratio of poloxamer 407 to glyceryl monoolein were selected as the factors that were used to optimize the dependent variables, which included encapsulation efficiency and drug loading. A three-factor, five-level central composite design was constructed to optimize the formulation. TET-loaded LCNPs (TET-LCNPs) were characterized to determine their particle size, zeta potential, entrapment efficiency, drug loading capacity, particle morphology, inner crystalline structure, and in vitro drug release profile. Corneal permeation in excised rabbit corneas was evaluated. Pre-ocular retention was determined using a noninvasive fluorescence imaging system. Finally, pharmacokinetic study in the aqueous humor was performed by microdialysis technique. The optimal formulation had a mean particle size of 170.0 +/- 13.34 nm, a homogeneous distribution with polydispersity index of 0.166 +/- 0.02, a positive surface charge with a zeta potential of 29.3 +/- 1.25 mV, a high entrapment efficiency of 95.46 +/- 4.13 %, and a drug loading rate of 1.63 +/- 0.07 %. Transmission electron microscopy showed spherical particles that had smooth surfaces. Small-angle X-ray scattering profiles revealed an inverted hexagonal phase. The in vitro release assays showed a sustained drug release profile. A corneal permeation study showed that the apparent permeability coefficient of the optimal formulation was 2.03-fold higher than that of the TET solution. Pre-ocular retention capacity study indicated that the retention of LCNPs was significantly longer than that of the solution (p < 0.01). In addition, a pharmacokinetic study of rabbit aqueous humors demonstrated that the TET-LCNPs showed 2.65-fold higher ocular bioavailability than that of TET solution. In conclusion, a LCNP system could be a promising method for increasing the ocular bioavailability of TET by enhancing its retention time and permeation into the cornea. PMID- 27188975 TI - Atypical Location of a Bartholin Cyst in Adolescence. AB - BACKGROUND: Cystic lesions associated with the blockage of Bartholin gland ducts are frequently seen, but occurrence outside the normal vestibular localization is quite rare. CASE: A 16-year-old patient presented with a localized cystic lump approximately 4 cm in size on one of her labia minora. After an excision, she was diagnosed with an atypically localized Bartholin cyst. SUMMARY AND CONCLUSION: It is very difficult to make an early diagnosis for an atypically localized Bartholin cystic lesion in adolescence; it can be diagnosed only after a pathological examination. In the differential diagnosis of a vulvar lump, an atypically localized Bartholin cyst should also be considered as a possibility. PMID- 27188976 TI - Support networks for Chinese older immigrants accessing English health and social care services: the concept of Bridge People. AB - As Chinese immigrants in the United Kingdom age, they experience an increasing need to access health and care services. It has, however, been reported that older Chinese immigrants have difficulties in accessing these services. This study explored the experiences of this population in using health and care services and the strategies that they adopted to address their difficulties. A grounded theory method with a two-staged research design was used. Stage 1 explored the participants' experiences of ageing and use of health and social care services through focus group interviews. Stage 2 investigated the strategies individuals used to support access to and use of services through individual interviews. Forty-four older Chinese people and 15 supporters participated in interviews during August 2011 and May 2013. These older Chinese immigrants were challenged in knowing about and in accessing services. Their difficulties were attributed to language barriers, lack of information and instrumental support, and emotional and cultural issues regarding use of health and care services. Their supporters facilitated access to services and acted as a bridge between the service and the user; therefore, they were given the title 'Bridge People'. Bridge People have different backgrounds: family and friends, public sector workers and staff from community-based Chinese organisations. The defining attributes of these supporters were: bilinguality, bicultural, multifunctionality and accessibility. There is no charge for this support; and the relationship between the Bridge Person and recipient involves trust and influence over decisions regarding use of health and care services. Bridge People should be recognised and identified by health, social care and housing services to promote engagement and use of services by older immigrant Chinese people. PMID- 27188977 TI - Pain management in critically ill patients: a review of multimodal treatment options. AB - Pain management for critically ill patients provides physicians with the challenge of maximizing patient comfort while avoiding the risks that arise with oversedation. Preventing oversedation has become increasingly important as we better understand the negative impact it has on patients' experiences and outcomes. Current research suggests that oversedation can result in complications such as thromboembolism, pulmonary compromise, immunosuppression and delirium. Fortunately, the analgesic options available for physicians to limit these complications are growing as more treatment modalities are being researched and implemented in the intensive care unit. Our goal is to outline some of the effective and widely utilized tools available to physicians to appropriately and safely manage pain while avoiding oversedation in the critically ill population. PMID- 27188980 TI - Pressing movements and perceived force and displacement are influenced by object stiffness. AB - Despite many previous studies on stiffness perception, few have investigated the exploratory procedures involved. This study evaluated whether stiffness range influences pressing movements and perception of force and displacement during stiffness discrimination tasks. Force and displacement data were obtained from 30 participants. Peak values of force and displacement, pressing duration and number of presses were analyzed. Two kinds of subjective evaluations were also recorded: perceived difference in force/displacement used to discriminate between specimens, and perceived effort. Although the number of presses and pressing duration were constant across a wide stiffness range, pressing strength was adjusted for the stiffness of objects, with harder specimens pressed more strongly. Further, even if the stiffnesses of two compared specimens were different, the pressing forces applied to the specimens approached the same magnitude at a higher stiffness range. Differences in force were most easily perceived at lower stiffness ranges, while displacement differences were perceived more readily at higher stiffness ranges. These results were consistent with those of previous studies. Finally, the reasons why stiffness range influenced pressing movements and perceived differences in force/displacement are discussed. PMID- 27188978 TI - Identification of proliferative progenitors associated with prominent postnatal growth of the pons. AB - The pons controls crucial sensorimotor and autonomic functions. In humans, it grows sixfold postnatally and is a site of paediatric gliomas; however, the mechanisms of pontine growth remain poorly understood. We show that the murine pons quadruples in volume postnatally; growth is fastest during postnatal days 0 4 (P0-P4), preceding most myelination. We identify three postnatal proliferative compartments: ventricular, midline and parenchymal. We find no evidence of postnatal neurogenesis in the pons, but each progenitor compartment produces new astroglia and oligodendroglia; the latter expand 10- to 18-fold postnatally, and are derived mostly from the parenchyma. Nearly all parenchymal progenitors at P4 are Sox2(+)Olig2(+), but by P8 a Sox2(-) subpopulation emerges, suggesting a lineage progression from Sox2(+) 'early' to Sox2(-) 'late' oligodendrocyte progenitor. Fate mapping reveals that >90% of adult oligodendrocytes derive from P2-P3 Sox2(+) progenitors. These results demonstrate the importance of postnatal Sox2(+)Olig2(+) progenitors in pontine growth and oligodendrogenesis. PMID- 27188981 TI - Individual differences in cortisol stress response predict increases in voice pitch during exam stress. AB - Despite a long history of empirical research, the potential vocal markers of stress remain unclear. Previous studies examining speech under stress most consistently report an increase in voice pitch (the acoustic correlate of fundamental frequency, F0), however numerous studies have failed to replicate this finding. In the present study we tested the prediction that these inconsistencies are tied to variation in the severity of the stress response, wherein voice changes may be observed predominantly among individuals who show a cortisol stress response (i.e., an increase in free cortisol levels) above a critical threshold. Voice recordings and saliva samples were collected from university psychology students at baseline and again immediately prior to an oral examination. Voice recordings included both read and spontaneous speech, from which we measured mean, minimum, maximum, and the standard deviation in F0. We observed an increase in mean and minimum F0 under stress in both read and spontaneous speech, whereas maximum F0 and its standard deviation showed no systematic changes under stress. Our results confirmed that free cortisol levels increased by an average of 74% (ranging from 0 to 270%) under stress. Critically, increases in cortisol concentrations significantly predicted increases in mean F0 under stress for both speech types, but did not predict variation in F0 at baseline. On average, stress-induced increases in voice pitch occurred only when free cortisol levels more than doubled their baseline concentrations. Our results suggest that researchers examining speech under stress should control for individual differences in the magnitude of the stress response. PMID- 27188979 TI - Enhanced neural response to anticipation, effort and consummation of reward and aversion during bupropion treatment. AB - BACKGROUND: We have previously shown that the selective serotonergic reuptake inhibitor, citalopram, reduces the neural response to reward and aversion in healthy volunteers. We suggest that this inhibitory effect might underlie the emotional blunting reported by patients on these medications. Bupropion is a dopaminergic and noradrenergic reuptake inhibitor and has been suggested to have more therapeutic effects on reward-related deficits. However, how bupropion affects the neural responses to reward and aversion is unclear. METHOD: Seventeen healthy volunteers (9 female, 8 male) received 7 days bupropion (150 mg/day) and 7 days placebo treatment, in a double-blind crossover design. Our functional magnetic resonance imaging task consisted of three phases; an anticipatory phase (pleasant or unpleasant cue), an effort phase (button presses to achieve a pleasant taste or to avoid an unpleasant taste) and a consummatory phase (pleasant or unpleasant tastes). Volunteers also rated wanting, pleasantness and intensity of the tastes. RESULTS: Relative to placebo, bupropion increased activity during the anticipation phase in the ventral medial prefrontal cortex (vmPFC) and caudate. During the effort phase, bupropion increased activity in the vmPFC, striatum, dorsal anterior cingulate cortex and primary motor cortex. Bupropion also increased medial orbitofrontal cortex, amygdala and ventral striatum activity during the consummatory phase. CONCLUSIONS: Our results are the first to show that bupropion can increase neural responses during the anticipation, effort and consummation of rewarding and aversive stimuli. This supports the notion that bupropion might be beneficial for depressed patients with reward-related deficits and blunted affect. PMID- 27188982 TI - Rotating carbon nanotube membrane filter for water desalination. AB - We have designed a porous nanofluidic desalination device, a rotating carbon nanotube membrane filter (RCNT-MF), for the reverse osmosis desalination that can turn salt water into fresh water. The concept as well as design strategy of RCNT MF is modeled, and demonstrated by using molecular dynamics simulation. It has been shown that the RCNT-MF device may significantly improve desalination efficiency by combining the centrifugal force propelled reverse osmosis process and the porous CNT-based fine scale selective separation technology. PMID- 27188983 TI - Obstetric benefits of health insurance: A comparative analysis of obstetric indices and outcome of enrollees and non-enrollees in southeast Nigeria. AB - This study determined the obstetric benefits and compared the obstetric indices and pregnancy outcome of enrollees and non-enrollees of the national health insurance scheme (NHIS). A prospective cohort study of enrollees and non enrollees of NHIS was conducted over 2 years. Data was analysed with Epi-info statistical software. Malaria (25.3% versus 8.0%, p value <=0.001), anaemia (11.3% versus 3.3%, p value <=0.0001), preterm delivery (8.0% versus 2.7% p value = 0.00001), antenatal default rate (22.7% versus 6.7%, p value = 0.0001) and maternal death (2.7% versus 0.7%, p value = 0.00001) were higher in the non insured. Singleton low birth weight (9.3% versus 2.7%, p value = 0.00001) and new born admission (10.7% versus 4.7%, p value = 0.00001) were also more in non enrollee, with higher perinatal deaths (6.7% versus 2.0%, p value = 0.00001). Women managed under the Nigerian NHIS scheme had better maternal and perinatal indices, therefore, effort should be scaled up to ensure universal health insurance coverage for all parturient and their newborn. PMID- 27188984 TI - Selective forces and mutational biases drive stop codon usage in the human genome: a comparison with sense codon usage. AB - BACKGROUND: The three stop codons UAA, UAG, and UGA signal the termination of mRNA translation. As a result of a mechanism that is not adequately understood, they are normally used with unequal frequencies. RESULTS: In this work, we showed that selective forces and mutational biases drive stop codon usage in the human genome. We found that, in respect to sense codons, stop codon usage was affected by stronger selective forces but was less influenced by neutral mutational biases. UGA is the most frequent termination codon in human genome. However, UAA was the preferred stop codon in genes with high breadth of expression, high level of expression, AT-rich coding sequences, housekeeping functions, and in gene ontology categories with the largest deviation from expected stop codon usage. Selective forces associated with the breadth and the level of expression favoured AT-rich sequences in the mRNA region including the stop site and its proximal 3' UTR, but acted with scarce effects on sense codons, generating two regions, upstream and downstream of the stop codon, with strongly different base composition. By favouring low levels of GC-content, selection promoted labile local secondary structures at the stop site and its proximal 3'-UTR. The compositional and structural context favoured by selection was surprisingly emphasized in the class of ribosomal proteins and was consistent with sequence elements that increase the efficiency of translational termination. Stop codons were also heterogeneously distributed among chromosomes by a mechanism that was strongly correlated with the GC-content of coding sequences. CONCLUSIONS: In human genome, the nucleotide composition and the thermodynamic stability of stop codon site and its proximal 3'-UTR are correlated with the GC-content of coding sequences and with the breadth and the level of gene expression. In highly expressed genes stop codon usage is compositionally and structurally consistent with highly efficient translation termination signals. PMID- 27188985 TI - Identification of biomarkers for development of end-stage kidney disease in chronic kidney disease by metabolomic profiling. AB - A critical issue in the management of chronic kidney disease (CKD) is to prevent patients from the progression to end-stage kidney disease (ESKD), however, there is only limited number of biomarkers for the discrimination of the high-risk CKD patients. We aimed to identify the metabolites which possess the ability to predict the earlier kidney deterioration. We performed capillary electrophoresis and liquid chromatography mass spectrometry (CE-MS)-based metabolic profiling in a prospective cohort, which consisted of referred 112 CKD patients with median follow-up period of 4.4 years. The association between the levels of candidate metabolites and the outcomes (progression to ESKD alone or in combination with death before ESKD) were assessed by multivariate Cox proportional hazard models after adjusting for the baseline covariates. A total of 218 metabolites were detected in the plasma of CKD patients. We identified 16 metabolites which have predictive values for the composite outcome: The risk for composite outcome was elevated from 2.0- to 8.0-fold in those with higher levels of 16 plasma metabolites. Our results suggest that the measurement of these metabolites may facilitate CKD management by predicting the risk of progression to ESKD. PMID- 27188986 TI - Neurofilament light chain in FTD is elevated not only in cerebrospinal fluid, but also in serum. PMID- 27188989 TI - Boron difluorides with formazanate ligands: redox-switchable fluorescent dyes with large stokes shifts. AB - The synthesis of a series of (formazanate)boron difluorides and their 1-electron reduction products is described. The neutral compounds are fluorescent with large Stokes shifts. DFT calculations suggest that a large structural reorganization accompanies photoexictation and accounts for the large Stokes shift. Reduction of the neutral boron difluorides occurs at the ligand and generates the corresponding radical anions. These complexes are non-fluorescent, allowing switching of the emission by changing the ligand oxidation state. PMID- 27188988 TI - The antioxidant activity of some curcuminoids and chalcones. AB - The antioxidant properties of the synthetic compound (C1)-(C8), which comprised 7 curcuminoids and a chalcone, were evaluated by two complementary assays, DPPH and beta-carotene/linoleic acid. It was found that, in general, the free radical scavenging ability of (C1)-(C8) was concentration-dependent. Compounds (C1) and (C4), which contained (4-OH) phenolic groups, were found to be highly potent antioxidants with higher antioxidant values than BHT suggesting that synthetic curcuminoids are more potent antioxidants than standard antioxidants like BHT. Using beta-carotene-linoleic acid assay, only the water-soluble 2, 4,6 trihydroxyphenolic chalcone (C5) showed 85.2 % inhibition of the formation of conjugated dienes reflecting on its potent antioxidant activity. PMID- 27188990 TI - The Prevalence and Characteristics of Charles Bonnet Syndrome in Turkish Patients with Retinal Disease. AB - PURPOSE: The aim of this study is to investigate the prevalence and clinical characteristics of Charles Bonnet syndrome (CBS) in a group of Turkish patients with various retinal diseases. METHODS: Two hundred and sixty-four patients with a best-corrected visual acuity of <=20/40 in the better-seeing eye were asked with a standardized question whether they had symptoms of CBS. If they responded positively, a questionnaire was verbally administered to learn more about the details of the symptoms. RESULTS: There were 125 (47.3%) females and 139 (52.7%) males with a mean age of 72.1 years (range 31-90). Seventeen (6.4%) patients were diagnosed with CBS. Three (17.7%) patients had noncomplex hallucinations and 14 (82.3%) had complex hallucinations. CONCLUSION: CBS is not uncommon in visually impaired patients with retinal disease. Clinicians who care for visually impaired patients should be aware of CBS. PMID- 27188987 TI - Alkylglycerols reduce serum complement and plasma vascular endothelial growth factor in obese individuals. AB - Alkylglycerols (AKGs), isolated or present in shark liver oil have anti inflammatory properties. Complement 3 (C3) and 4 (C4) participate in lipid metabolism and in obesity, contributing to the metabolic syndrome and to the low grade inflammation associated with obesity. In a randomized, controlled, crossover study, 26 non-diabetes obese individuals were assigned two preparations with low (LAC, 10 mg AKGs) and high (HAC, 20 mg AKGs) AKG content. Intervention periods were of 3 weeks preceded by 2-week washout periods in which shark liver oil was avoided. Cholesterol, C3, C4, and vascular endothelial growth factor (VEGF) decreased in a linear trend (P < 0.01) from baseline (control) to LAC and HAC. Values after HAC were significantly lower (P < 0.05) versus both baseline and after LAC. No adverse effects were observed or reported. Data from this pilot study open a promising field for the study of the beneficial effects of AKGs on cardiovascular risk factors in obese individuals. PMID- 27188991 TI - What proportion of Salmonella Typhi cases are detected by blood culture? A systematic literature review. AB - Blood culture is often used in definitive diagnosis of typhoid fever while, bone marrow culture has a greater sensitivity and considered reference standard. The sensitivity of blood culture measured against bone marrow culture results in measurement bias because both tests are not fully sensitive. Here we propose a combination of the two cultures as a reference to define true positive S. Typhi cases. Based on a systematic literature review, we identified ten papers that had performed blood and bone marrow culture for S. Typhi in same subjects. We estimated the weighted mean of proportion of cases detected by culture measured against true S. Typhi positive cases using a random effects model. Of 529 true positive S. Typhi cases, 61 % (95 % CI 52-70 %) and 96 % (95 % CI 93-99 %) were detected by blood and bone marrow cultures respectively. Blood culture sensitivity was 66 % (95 % CI 56-75 %) when compared with bone marrow culture results. The use of blood culture sensitivity as a proxy measure to estimate the proportion of typhoid fever cases detected by blood culture is likely to be an underestimate. As blood culture sensitivity is used as a correction factor in estimating typhoid disease burden, epidemiologists and policy makers should account for the underestimation. PMID- 27188993 TI - [Concurrent achalasia and severe obesity]. AB - Achalasia is a rare oesophageal motility disorder which classically is not associated with obesity. We present the case of a 50-year-old woman who underwent gastric bypass and afterwards was diagnosed with achalasia. Following, she was treated successfully with peroral endoscopic myotomy (POEM). A thorough medical history revealed that symptoms of achalasia had been present for 25 years and were the cause of inappropriate eating habits and consequently morbid obesity. This case story illustrates the importance of being aware of simultaneous occurrence of achalasia and morbid obesity. Furthermore, it demonstrates that POEM is safe and effective for symptomatic relief of achalasia after previous gastric bypass. PMID- 27188992 TI - [Acute aortic syndrome]. AB - Acute aortic syndrome is a group of pathogenic conditions including aortic dissection, intramural haematoma, penetrating ulcer and aortic aneurysm. The syndrome is a challenging clinical diagnosis because the symptoms are numerous and diverse with similarity to other more common conditions. Delayed diagnosis and treatment can be fatal. Computed tomography angiography is the most important diagnostic tool and is the first choice when acute aortic syndrome is suspected. With this article, we wish to raise awareness of the incidence of acute aortic syndrome and the clinical features of the syndrome. PMID- 27188994 TI - [Sleep impairment is a threat to good health]. AB - Long-term sleep impairment is related to an increased risk of somatic health problems, e.g. overweight, Type 2 diabetes, cardiovascular disease and premature death. Avoidance of caffeine, alcohol, energy-rich or fatty foods and light from computer screens close to bedtime may counteract impaired sleep. A quiet, dark and well-tempered bedroom and physical activity during the day may have a positive impact on sleep. Impaired sleep may be related to stress and conditions at home or at work. Psychological sleep treatment is free of adverse side effects with effects comparable to effects of medical treatment. PMID- 27188995 TI - [Harlekinsyndrom]. PMID- 27188996 TI - Flavobacterium fulvum sp. nov., Flavobacterium pedocola sp. nov. and Flavobacterium humicola sp. nov., three new members of the family Flavobacteriaceae, isolated from soil. AB - Four Gram-stain-negative, non-endospore-forming, non-motile strains were found in soil, South Korea. Based on their 16S rRNA gene sequences, strains UCM-R15T and UCM-R21 are most closely related to Flavobacterium enshiense DK69T (97.4-97.5 %, pairwise similarity) while strains UCM-R36T and UCM-46T are most closely related to Flavobacterium suncheonense GH29-5T (97.5 % and 98.3 %, respectively), with all four strains sharing less than 97 % pairwise similarity to the type strain of any other species of the genus Flavobacterium. None of the four strains can reduce/digest nitrate or urea. The only menaquinone detected was MK-6 and the major fatty acids were iso-C15 : 0, iso-C17 : 0 3-OH, iso-C15 : 1 G and summed feature 9 in all the type strains. Phosphatidylethanolamine was found in three strains as the major polar lipid, phosphatidylserine was found in both strains UCM-R15T and UCM-R36T, but not UCM-46T, and phosphatidylmonomethylethanolamine only occurred in strain UCM-R15T. The genomic DNA G+C content values of strains UCM-R15T, UCM-R21, UCM-R36T and UCM-46T were 35.3-39.0 mol%. Taking into account their physiological and biochemical characteristics, we suggest that three of the strains are novel members of the genus Flavobacterium. We propose the names Flavobacterium fulvum sp. nov. for type strain UCM-R15T (=KACC 18666T=NBRC 111764T), and strain UCM-R21 as an additional strain Flavobacterium pedocola sp. nov. for type strain UCM-R36T (=KACC 18668T=NBRC 111765T), and Flavobacterium humicola sp. nov. for type strain UCM-46T (=KACC 18575T=NBRC 111657T). PMID- 27188997 TI - Impaired CD8(+) T cell responses upon Toll-like receptor activation in common variable immunodeficiency. AB - BACKGROUND: Infections caused by bacteria or viruses are frequent in common variable immunodeficiency (CVID) patients due to antibody deficiencies, which may be associated with altered T cell function. CVID patients are frequently in contact with pathogen-associated molecular patterns (PAMPs), leading to the activation of innate immunity through Toll-like receptors (TLR) affecting T cell activation. We evaluated the effect of TLR activation on T cells in CVID patients undergoing intravenous immunoglobulin (IVIg) replacement using synthetic ligands. METHODS: Expression of exhaustion, activation and maturation markers on T cells from peripheral blood as well as regulatory T cells and follicular T cells in peripheral blood mononuclear cells (PBMCs) from CVID and healthy individuals were evaluated by flow cytometry. PBMCs cultured with TLR agonists were assessed for intracellular IFN-gamma, TNF, IL-10, IL-17a or IL-22 secretion as monofunctional or polyfunctional T cells (simultaneous cytokine secretion) by flow cytometry. RESULTS: We found increased expression of the exhaustion marker PD-1 on effector memory CD4(+) T cells (CD45RA(-)CCR7(-)) in the peripheral blood and increased expression of CD38 in terminally differentiated CD8(+) T cells (CD45RA(+)CCR7( )). Furthermore, a decreased frequency of naive regulatory T cells (CD45RA(+)Foxp3(low)), but not of activated regulatory T cells (CD45RA( )Foxp3(high)) was detected in CVID patients with splenomegaly, the non-infectious manifestation in this CVID cohort (43.7 %). Moreover, the frequency of peripheral blood follicular helper T cells (CD3(+)CD4(+)CXCR5(+)PD-1(+)ICOS(+)) was similar between the CVID and control groups. Upon in vitro TLR3 activation, a decreased frequency of CD8(+) T cells secreting IFN-gamma, IL-17a or IL-22 was detected in the CVID group compared to the control group. However, a TLR7/TLR8 agonist and staphylococcal enterotoxin B induced an increased Th22/Tc22 (IL-22(+), IFN-gamma( ), IL-17a(-)) response in CVID patients. Both TLR2 and TLR7/8/CL097 activation induced an increased response of CD4(+) T cells secreting three cytokines (IL 17a, IL-22 and TNF)in CVID patients, whereas CD8(+) T cells were unresponsive to these stimuli. CONCLUSION: The data show that despite the unresponsive profile of CD8(+) T cells to TLR activation, CD4(+) T cells and Tc22/Th22 cells are responsive, suggesting that activation of innate immunity by TLRs could be a strategy to stimulate CD4(+) T cells in CVID. PMID- 27188998 TI - An SNP site in pri-miR-124, a brain expressed miRNA gene, no contribution to mesial temporal lobe epilepsy in an Italian sample. AB - Mesial temporal lobe epilepsy (MTLE) is the most common type of refractory epilepsy and is usually associated with hippocampal sclerosis (Hs). The pathogenesis of MTLE involves many biological pathways, some of which seem to be regulated by microRNAs (miRNAs). Increasing evidence shows that single nucleotide polymorphisms (SNPs) or mutations in miRNAs sequence may affect the processing and function of miRNAs and participate in the occurrence of diseases. In this study, the effect of the SNP of one neuronal miRNA, miR-124, on susceptibility to MTLE was investigated using a case control study. To understand the role, a common C/G polymorphism designated rs531564 in the molecular mechanisms of MTLE, we sought to determine whether this genetic variant could influence susceptibility to disease in a cohort of 307 MTLE patients and 306 healthy controls, using TaqMan allelic discrimination assay, on an Applied Biosystems PCR platform. No statistically significant differences were found in the allele or genotype distributions of the miR-124 rs531564 polymorphism among MTLE patients and MTLE-free control subjects (p > 0.05). Our results demonstrate that this SNP has no major role in genetic susceptibility to MTLE, at least in the population studied here. PMID- 27188999 TI - Association between the IL7R T244I polymorphism and multiple sclerosis risk: a meta analysis. AB - The aim of this study was to explore the association between the IL7R T244I polymorphism (rs6897932) and susceptibility of multiple sclerosis (MS). A comprehensive literature search for relevant studies was conducted on Google scholar, PubMed, the Chinese National Knowledge Infrastructure (CNKI) and the Chinese Biomedical Literature Database (CBM). This meta-analysis was performed using the STATA 11.0 software and the pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated. Seventeen case-control studies were included in this meta-analysis. In total, 17 articles provided data for 15,270 cases and 17,971 controls. The results showed significant association between the IL7R T244I polymorphism and susceptibility to MS (OR = 1.125, 95 % CI: 1.016-1.245, p = 0.024 for C vs. T; OR = 1.176, 95 % CI: 1.078-1.282, p < 0.001 for CC + CT vs. TT; OR = 1.243, 95 % CI: 1.088-1.421, p = 0.001 for CC vs. TT). Stratified analysis of ethnicities also showed significant association in Europeans. However, no association was found in Asians. This study suggested that the IL7R C allele was associated with an increased risk of MS and larger-scale studies of populations are needed to explore the roles played by the IL7R T244I polymorphism during the pathogenesis of MS. PMID- 27189000 TI - Late mortality after sepsis: propensity matched cohort study. AB - OBJECTIVES: To determine whether late mortality after sepsis is driven predominantly by pre-existing comorbid disease or is the result of sepsis itself. DEIGN: Observational cohort study. SETTING: US Health and Retirement Study. PARTICIPANTS: 960 patients aged >=65 (1998-2010) with fee-for-service Medicare coverage who were admitted to hospital with sepsis. Patients were matched to 777 adults not currently in hospital, 788 patients admitted with non-sepsis infection, and 504 patients admitted with acute sterile inflammatory conditions. MAIN OUTCOME MEASURES: Late (31 days to two years) mortality and odds of death at various intervals. RESULTS: Sepsis was associated with a 22.1% (95% confidence interval 17.5% to 26.7%) absolute increase in late mortality relative to adults not in hospital, a 10.4% (5.4% to 15.4%) absolute increase relative to patients admitted with non-sepsis infection, and a 16.2% (10.2% to 22.2%) absolute increase relative to patients admitted with sterile inflammatory conditions (P<0.001 for each comparison). Mortality remained higher for at least two years relative to adults not in hospital. CONCLUSIONS: More than one in five patients who survives sepsis has a late death not explained by health status before sepsis. PMID- 27189001 TI - Parent-child proximity and personality: basic human values and moving distance. AB - BACKGROUND: An important event in many young people's lives is moving out of the parental home. This event is often operationalized as the distance between parents and their children, i.e., parent-child proximity. METHODS: The present study (N = 1,451) analyzed correlates of parent-child proximity through the lens of human value theory (Schwartz, Advances in experimental social psychology, 1992). Besides a classical proximity measure (i.e., parent-child), we also calculated the distance between childhood and current place of residence (i.e., childhood-now), as well as parent-childhood proximity (distance between children's childhood place of residence and the current place of residence of parents), which acts as a control group because this distance is most probably chosen by the parents. RESULTS: As hypothesized, we found that participants valuing universalism and self-direction as important (i.e., associated with growth and anxiety-freedom) moved further away from the place where their parents live and the place where they grew up than participants valuing self-protection and anxiety-avoidance (e.g., tradition, security, conformity). CONCLUSIONS: This study not only adds to research on psychological motivations to move, it endorses value theory as being a useful lens through which to analyze migration behavior. PMID- 27189004 TI - Projection of Romantic and Sexual Desire in Opposite-Sex Friendships: How Wishful Thinking Creates a Self-Fulfilling Prophecy. AB - In two studies, the authors examined the projection of romantic and sexual desire in opposite-sex friendships. In both studies, perceivers who strongly desired their friends projected this desire onto their friends, believing that their desire was more reciprocated than was actually the case. In turn, projection of desire appeared to motivate perceivers into enacting relationship initiation behaviors, which predicted changes in targets' romantic and sexual desires over time (Study 2). Projection was elevated for perceivers who saw themselves as high in mate value, and targets appeared to be influenced by perceivers' overtures primarily when they believed perceivers were high in mate value. This research suggests that, for perceivers high in mate value, romantic and sexual desire creates biased perceptions that initiate self-fulfilling prophecies. PMID- 27189003 TI - Erratum to: QTL mapping of carrot resistance to leaf blight with connected populations: stability across years and consequences for breeding. PMID- 27189002 TI - Detecting the QTL-allele system of seed isoflavone content in Chinese soybean landrace population for optimal cross design and gene system exploration. AB - KEY MESSAGE: Utilizing an innovative GWAS in CSLRP, 44 QTL 199 alleles with 72.2 % contribution to SIFC variation were detected and organized into a QTL-allele matrix for cross design and gene annotation. The seed isoflavone content (SIFC) of soybeans is of great importance to health care. The Chinese soybean landrace population (CSLRP) as a genetic reservoir was studied for its whole-genome quantitative trait loci (QTL) system of the SIFC using an innovative restricted two-stage multi-locus genome-wide association study procedure (RTM-GWAS). A sample of 366 landraces was tested under four environments and sequenced using RAD-seq (restriction-site-associated DNA sequencing) technique to obtain 116,769 single nucleotide polymorphisms (SNPs) then organized into 29,119 SNP linkage disequilibrium blocks (SNPLDBs) for GWAS. The detected 44 QTL 199 alleles on 16 chromosomes (explaining 72.2 % of the total phenotypic variation) with the allele effects (92 positive and 107 negative) of the CSLRP were organized into a QTL allele matrix showing the SIFC population genetic structure. Additional differentiation among eco-regions due to the SIFC in addition to that of genome wide markers was found. All accessions comprised both positive and negative alleles, implying a great potential for recombination within the population. The optimal crosses were predicted from the matrices, showing transgressive potentials in the CSLRP. From the detected QTL system, 55 candidate genes related to 11 biological processes were chi (2)-tested as an SIFC candidate gene system. The present study explored the genome-wide SIFC QTL/gene system with the innovative RTM-GWAS and found the potentials of the QTL-allele matrix in optimal cross design and population genetic and genomic studies, which may have provided a solution to match the breeding by design strategy at both QTL and gene levels in breeding programs. PMID- 27189007 TI - Great tumour burden in the axilla may influence lymphatic drainage in breast cancer patients. AB - We investigated whether great tumour burden in the primary draining lymph node would lead to obstructed lymphatic flow in breast cancer patients. Breast cancer patients with false-negative sentinel lymph nodes (SLNs) were enrolled from January 2001 to March 2011, retrospectively. A further 45 breast cancer patients were recruited prospectively from December 2013 to November 2014. Carbon nanoparticles, a lymphatic tracer, were injected into the subareolar area 24 h before surgery, followed by axillary lymph node dissection. In the SLN cohort, among the 28 false-negative cases, >50 % showed great tumour burden in the axilla. In the carbon nanoparticles cohort, we found that cases with <3 nodes involved in the pathology had more lymph nodes stained by carbon nanoparticles than the subgroup with >=3 involved nodes (P = 0.003). Nodes stained with carbon nanoparticles showed smaller tumour burdens compared with unstained nodes (P < 0.05). Furthermore, five cases showed metastatic nodes that were not stained with carbon nanoparticles, and all the lymph nodes that were free of metastasis were stained with carbon nanoparticles. Great tumour burden in the axilla might lead to lymphatic flow obstructions in clinical practice. Nevertheless, clinical trials are still needed to validate our findings. PMID- 27189005 TI - Health-related quality of life and clinical outcomes following medial open wedge high tibial osteotomy: a prospective study. AB - BACKGROUND: Open wedge high tibial osteotomy (HTO) is an established method for the treatment of patients with varus malalignment and medial compartment osteoarthritis. In these patients, health-related quality of life (HRQL) can be improved by using this procedure. The purpose of the present study consisted in evaluating HRQL up to 18 months after HTO, comparing the results to values of the German normal population, and in analyzing the impact of preoperative HRQL on the postoperative clinical result. It was hypothesized that normal values in physical and mental health can be achieved within 18 months after operation. STUDY DESIGN: Prospective case series. LEVEL OF EVIDENCE: IV. METHODS: 120 patients were included in this prospective case series from 12/2008 to 12/2011. All patients underwent open wedge HTO without a bone graft using the TomoFix(TM) plate. HRQL was assessed by using the SF-36 questionnaire, preoperatively, as well as 6, 12, and 18 months postoperatively. Regular scoring, norm-based scaling, and the physical and mental component summary scores (PCS and MCS) were evaluated. Clinical outcome was assessed by using Lequesne, Lysholm, HSS and IKDC Score. RESULTS: HRQL could be described in 96 patients. The PCS of HRQL showed a statistically significant pre- to postoperative improvement (30.2 +/- 13.4 to 45.9 +/- 13.5 after 18 months). A reduced preoperative mental component summary score (MCS) resulted in lower values of each clinical score (p < 0.05) and in a prolonged duration of incapacity for work (MCS < 50:15.0 +/- 12.8 weeks, vs. MCS >= 50: 9.1 +/- 4.8 weeks, p < 0.05). MCS values improved from the pre- to postoperative measurements and comparable values to the normal population were reached already within 6 months after surgery (46.0 +/- 14.9 pre-operatively and 48.5 +/- 13.7 after 6 months), and after 18 months even a score of 49.5 +/- 12.4 was achieved. CONCLUSION: Lower preoperative mental component score results in reduced postoperative clinical outcome and prolonged duration of incapacity for work after HTO. In contrast to PCS, MCS showed comparable values to the normal population within 6 months after HTO. PMID- 27189008 TI - Real-world outcomes in young women with breast cancer treated with neoadjuvant chemotherapy. AB - Breast cancer in young women has been shown to have an aggressive behavior and worse prognosis. Studies evaluating young women enrolled in clinical trials of neoadjuvant chemotherapy have shown that age is a determinant factor in the achievement of a pathological complete response (pCR). In this study, we sought to analyze the outcomes of young patients treated with neoadjuvant chemotherapy at a single institution. 1639 patients treated with neoadjuvant chemotherapy were included. 316 patients <=40 years were compared with 1323 patients aged >40 years regarding the achievement of a pCR (defined as no invasive residual tumor in the breast or lymph nodes). Disease-free survival (DFS) and overall survival were compared between groups according to pCR status and subtype, defined by hormone receptor (HR) and HER2 status. Young women were more likely to have a pCR than their older counterparts (37.4 vs. 26.3 %, P < 0.001). This difference was significant both for HR+/HER2- and triple-negative (TN) tumors. Young age and achieving less than pCR were associated with a greater chance of recurrence for the entire population. Age was not an independent factor for recurrence in TN and HER2+ disease. However, being younger than 40 increased recurrence risk in HR+/HER2- tumors. The achievement of a pCR was not associated with improved DFS in young women with HR+/HER2- tumors. Although young women have a high rate of pCR, they also have a worse prognosis. In a real-world clinical setting, the achievement of a pCR was an independently significant protective factor for recurrence across all subtypes and ages, except for HR+, HER2- disease in young women. PMID- 27189009 TI - Genetic and root phenotype diversity in Sri Lankan rice landraces may be related to drought resistance. AB - BACKGROUND: The development of relatively cheap and high throughput methods of genotyping and phenotyping plants offers the opportunity to explore local germplasm more thoroughly than before and should accelerate the identification of sources of genetic variation suitable for breeding. In this study, 135 Sri Lankan accessions, mostly identified as landraces, for which data was available at the International Rice Research Institute on drought scores were genotyped using a 384 SNP array and assessed for root depth using a newly developed buried herbicide method. Roots of 36 accessions were assessed using hydroponics and 12 using soil-filled rhizotrons to establish if variation in herbicide score could be attributed to root traits. RESULTS: Population structure based on the SNPs using STRUCTURE revealed six groups, being tropical japonica, aus and four indica subpopulations. Three of these indica subpopulations do not seem to be represented in the Rice Diversity Panel I (RDP1) of 372 global rice accessions and appear to represent genetic diversity so far poorly studied by the global scientific community. The herbicide score was highly discriminatory between landraces and correlated very strongly with hydroponic and rhizotron root traits. The mean herbicide score strongly differentiated between landraces according to the province and the latitude from which they were collected. It also differed between subpopulations, being high in indica 2 and tropical japonica and low in indica 1 and aus. Drought scores suggest that indica 2 is more drought resistant than the other groups. Correlations indicate that those landraces with high herbicide scores are more drought resistant in the vegetative stage. The landrace Niyan Wee, whose name in Sinhalese means "drought rice" belongs to the indica 2 subgroup, has high herbicide scores and deep roots. CONCLUSIONS: Niyan Wee and other cultivars within the indica 2 subgroup should be a valuable source of breeding for drought resistance at least partly because of their superior root traits, not normally associated with the indica rice cultivars. PMID- 27189006 TI - Identification and cloning of class II and III chitinases from alkaline floral nectar of Rhododendron irroratum, Ericaceae. AB - MAIN CONCLUSION: Class II and III chitinases belonging to different glycoside hydrolase families were major nectarins in Rhododendron irroratum floral nectar which showed significant chitinolytic activity. Previous studies have demonstrated antimicrobial activity in plant floral nectar, but the molecular basis for the mechanism is still poorly understood. Two chitinases, class II (Rhchi2) and III (Rhchi3), were characterized from alkaline Rhododendron irroratum nectar by both SDS-PAGE and mass spectrometry. Rhchi2 (27 kDa) and Rhchi3 (29 kDa) are glycoside hydrolases (family 19 and 18) with theoretical pI of 8.19 and 7.04. The expression patterns of Rhchi2 and Rhchi3 were analyzed by semi-quantitative RT-PCR. Rhchi2 is expressed in flowers (corolla nectar pouches) and leaves while Rhchi3 is expressed in flowers. Chitinase in concentrated protein and fresh nectar samples was visualised by SDS-PAGE and chitinolytic activity in fresh nectar was determined spectrophotometrically via chitin-azure. Full length gene sequences were cloned with Tail-PCR and RACE. The amino acid sequence deduced from the coding region for these proteins showed high identity with known chitinases and predicted to be located in extracellular space. Fresh R. irroratum floral nectar showed significant chitinolytic activity. Our results demonstrate that class III chitinase (GH 18 family) also exists in floral nectar. The functional relationship between class II and III chitinases and the role of these pathogenesis-related proteins in antimicrobial activity in nectar is suggested. PMID- 27189010 TI - Augmenting water supply by combined desalination/water recycling methods: an economic assessment. AB - Dry coastal communities increasingly need to consider non-traditional methods of augmenting their water supply. This study presents a preliminary economic comparison of three alternatives for increasing the water supply by 50% for a hypothetical baseline coastal scenario: increasing desalination (Scenario A), direct potable water reuse (DPWR) (Scenario B), and a novel retrofitted configuration of a hybrid forward osmosis-reverse osmosis (FO-RO) plant (Scenario C). The latter used the dilution of the seawater feed to increase the recovery and overall output water of the original RO step. To account for the time value of money, levelised cost (LC) was used as the primary economic metric. The hybrid FO-RO configuration had a comparable LC to DPWR (0.59 vs. 0.61 $ m-3) and was 12% cheaper than desalination (0.67 $ m-3). Furthermore, hybrid FO-RO was 7% more energy efficient than conventional desalination due to reduced intake and pretreatment flows. Sensitivity analyses demonstrated that incremental reductions in LC were possible for increased FO membrane flux, including in pressure assisted osmosis scenarios with applied pressure ranging from 2 to 6 bar. These findings validate the examination of hybrid FO-RO configurations that deviate from the energy-reduction paradigms typically studied. PMID- 27189011 TI - Treatment with a GnRH receptor agonist, but not the GnRH receptor antagonist degarelix, induces atherosclerotic plaque instability in ApoE(-/-) mice. AB - Androgen-deprivation therapy (ADT) for prostate cancer has been associated with increased risk for development of cardiovascular events and recent pooled analyses of randomized intervention trials suggest that this primarily is the case for patients with pre-existing cardiovascular disease treated with gonadotropin-releasing hormone receptor (GnRH-R) agonists. In the present study we investigated the effects of the GnRH-R agonist leuprolide and the GnRH-R antagonist degarelix on established atherosclerotic plaques in ApoE(-/-) mice. A shear stress modifier was used to produce both advanced and more stable plaques in the carotid artery. After 4 weeks of ADT, increased areas of necrosis was observed in stable plaques from leuprolide-treated mice (median and IQR plaque necrotic area in control, degarelix and leuprolide-treated mice were 0.6% (IQR 0 3.1), 0.2% (IQR 0-4.4) and 11.0% (IQR 1.0-19.8), respectively). There was also evidence of increased inflammation as assessed by macrophage immunohistochemistry in the plaques from leuprolide-treated mice, but we found no evidence of such changes in plaques from control mice or mice treated with degarelix. Necrosis destabilizes plaques and increases the risk for rupture and development of acute cardiovascular events. Destabilization of pre-existing atherosclerotic plaques could explain the increased cardiovascular risk in prostate cancer patients treated with GnRH-R agonists. PMID- 27189012 TI - Learning disease relationships from clinical drug trials. AB - OBJECTIVE: Our objective is to test the limits of the assumption that better learning from data in medicine requires more granular data. We hypothesize that clinical trial metadata contains latent scientific, clinical, and regulatory expert knowledge that can be accessed to draw conclusions about the underlying biology of diseases. We seek to demonstrate that this latent information can be uncovered from the whole body of clinical trials. MATERIALS AND METHODS: We extract free-text metadata from 93 654 clinical drug trials and introduce a representation that allows us to compare different trials. We then construct a network of diseases using only the trial metadata. We view each trial as the summation of expert knowledge of biological mechanisms and medical evidence linking a disease to a drug believed to modulate the pathways of that disease. Our network representation allows us to visualize disease relationships based on this underlying information. RESULTS: Our disease network shows surprising agreement with another disease network based on genetic data and on the Medical Subject Headings (MeSH) taxonomy, yet also contains unique disease similarities. DISCUSSION AND CONCLUSION: The agreement of our results with other sources indicates that our premise regarding latent expert knowledge holds. The disease relationships unique to our network may be used to generate hypotheses for future biological and clinical research as well as drug repurposing and design. Our results provide an example of using experimental data on humans to generate biologically useful information and point to a set of new and promising strategies to link clinical outcomes data back to biological research. PMID- 27189014 TI - Upper-Extremity Deep-Vein Thrombosis: A Retrospective Cohort Evaluation of Thrombotic Risk Factors at a University Teaching Hospital Antithrombosis Clinic. AB - BACKGROUND: Upper-extremity deep-vein thrombosis (UEDVT) causes significant morbidity and mortality and is not well characterized in the existing literature, particularly in underrepresented minorities such as African Americans. OBJECTIVE: To describe the characteristics of a cohort of patients with UEDVT seen at an urban academic medical center. METHODS: This was a retrospective cohort study among patients with a confirmed UEDVT at the University of Illinois Hospital and Health Sciences System between 1996 and 2011. Patients were identified by ICD-9 code for UEDVT. Variables collected include thrombotic risk factors and outcomes, including recurrent thrombosis and bleeding. RESULTS: We identified 229 patients with UEDVT; 71% were African American, and 11% were diagnosed with sickle cell disease. The average number of UEDVT risk factors was 4.40 +/- 1.5, the most common being central venous catheter (CVC) use (178, 78%). In the year following UEDVT, 13% experienced recurrent thrombosis, and 6% experienced major bleeding. Of 181 patients receiving warfarin after an UEDVT, 36% of international normalized ratio (INR) values were therapeutic. Patients with sickle cell disease had a lower proportion of INRs within the target range (25% vs 38%, P < 0.01), and were more likely to be lost to follow-up (67% vs 46%, P = 0.05) and experience a recurrent thrombotic event (29% vs 11%, P = 0.02). CONCLUSION: A CVC is the most common risk factor for UEDVT; however, patients with sickle cell disease demonstrate additional unique demographics and risk factors. Patients included in this underrepresented demographic cohort had a low quality of anticoagulation control, particularly those with sickle cell disease. PMID- 27189015 TI - Depletion of florfenicol in lactating dairy cows after intramammary and subcutaneous administration. AB - Eighteen Holstein dairy cows ranging in body weight from 500-700 kg and with an average milk yield of 37 +/- 6 kg/day were used to investigate the depletion of florfenicol (FFL) in milk and plasma of dairy cows. Three groups of six were administered FFL: Group A, intramammary (IMM) infusion of ~2.5 mg FFL/kg BW at three consecutive milking intervals (total amount of ~7.5 mg/kg BW); Group B, one IMM infusion (20 mg/kg BW) into one quarter and Group C, one subcutaneous (SC) treatment (40 mg/kg BW). IMM infusions were into the right front quarter. Cows were milked daily at 06:00 and 18:00 h. The highest concentrations (Cmax ) and time to Cmax (Tmax ) were: 1.6 +/- 2.2 MUg.FFL/mL milk at 22 h (Group A), 5.5 +/- 3.6 MUg.FFL/mL milk at 12 h (Group B), and 1.7 +/- 0.4 MUg.FFL/mL milk at 12 h (Group C). The half-lives (t1/2 ) were ~19, 5.5, and 60 h, for Groups A, B, and C, respectively. FFL was below the limit of detection (LOD) by 60 h in three Group B cows, but above the LOD at 72, 84, and 120 h in three cows. FFL was above the LOD in milk from Group C's cows for 432-588 h. Plasma values followed the same trends as milk. The results demonstrate that IMM-infused FFL is bioavailable and below the LOD within 72-120 h. The concentration of FFL was detectable in both plasma and milk over the course of 2-3 weeks after SC administration. The absence of residue depletion data presents problems in determining safe levels of FFL residues in milk and edible tissues. The data presented here must not be construed as approval for extra-label use in food animals. PMID- 27189016 TI - The Degree of Anisocytosis Predicts Survival in Patients with Primary Myelofibrosis. PMID- 27189013 TI - Opportunities and challenges in developing risk prediction models with electronic health records data: a systematic review. AB - OBJECTIVE: Electronic health records (EHRs) are an increasingly common data source for clinical risk prediction, presenting both unique analytic opportunities and challenges. We sought to evaluate the current state of EHR based risk prediction modeling through a systematic review of clinical prediction studies using EHR data. METHODS: We searched PubMed for articles that reported on the use of an EHR to develop a risk prediction model from 2009 to 2014. Articles were extracted by two reviewers, and we abstracted information on study design, use of EHR data, model building, and performance from each publication and supplementary documentation. RESULTS: We identified 107 articles from 15 different countries. Studies were generally very large (median sample size = 26 100) and utilized a diverse array of predictors. Most used validation techniques (n = 94 of 107) and reported model coefficients for reproducibility (n = 83). However, studies did not fully leverage the breadth of EHR data, as they uncommonly used longitudinal information (n = 37) and employed relatively few predictor variables (median = 27 variables). Less than half of the studies were multicenter (n = 50) and only 26 performed validation across sites. Many studies did not fully address biases of EHR data such as missing data or loss to follow up. Average c-statistics for different outcomes were: mortality (0.84), clinical prediction (0.83), hospitalization (0.71), and service utilization (0.71). CONCLUSIONS: EHR data present both opportunities and challenges for clinical risk prediction. There is room for improvement in designing such studies. PMID- 27189017 TI - Intraspecific morphometric variation in myxosporeans. AB - Morphometric data from spores of ten myxosporean species were statistically analysed to explore myxosporean intraspecific variation in measurements when obtained from a sample from: (1) the same plasmodium, (2) different plasmodia from the same host and (3) different host individuals and localities. In some cases, significant differences in spore dimensions were found between samples from the same plasmodium, highlighting the difficulty of obtaining representative measurements of myxosporean spore. In addition, significant differences in spore dimensions were found when plasmodia from the same site of infection were compared, suggesting that measurements of spores should come from several different plasmodia of the sampling to increase the reliability of the morphology data. Moreover, significant differences in spore dimensions were observed for most spore dimensions when data were compared between localities. In all cases, there was clear overlap in ranges of dimensions even when means differed significantly. The present statistical analysis shows that intraspecific morphometric variation of myxosporean species commonly occurs, highlighting the importance of reporting ranges of measurements for a species, not just the mean dimensions, and taking into account all evidence when assigning or describing myxosporean species. PMID- 27189018 TI - The Family Life Course and Health: Partnership, Fertility Histories, and Later Life Physical Health Trajectories in Australia. AB - Life course perspectives suggest that later-life health reflects long-term social patterns over an individual's life: in particular, the occurrence and timing of key roles and transitions. Such social patterns have been demonstrated empirically for multiple aspects of fertility and partnership histories, including timing of births and marriage, parity, and the presence and timing of a marital disruption. Most previous studies have, however, addressed particular aspects of fertility or partnership histories singly. We build on this research by examining how a holistic classification of family life course trajectories from ages 18 to 50, incorporating both fertility and partnership histories, is linked to later-life physical health for a sample of Australian residents. Our results indicate that long-term family life course trajectories are strongly linked to later-life health for men but only minimally for women. For men, family trajectories characterized by early family formation, no family formation, an early marital disruption, or high fertility are associated with poorer physical health. Among women, only those who experienced both a disrupted marital history and a high level of fertility were found to be in poorer health. PMID- 27189019 TI - Clinical Utility Gene Card for: Congenital Generalized Lipodystrophy. PMID- 27189020 TI - The effect of a decision aid on informed decision-making in the era of non invasive prenatal testing: a randomised controlled trial. AB - Early in pregnancy women and their partners face the complex decision on whether or not to participate in prenatal testing for fetal chromosomal abnormalities. Several studies show that the majority of pregnant women currently do not make informed decisions regarding prenatal testing. As the range of prenatal tests is expanding due to the development of new techniques such as non-invasive prenatal testing (NIPT), autonomous reproductive decision-making is increasingly challenging. In this study, a randomised controlled trial was conducted to evaluate the effect of a web-based multimedia decision aid on decision-making regarding prenatal testing. The decision aid provided both written and audiovisual information on prenatal tests currently available, that is, prenatal screening by first-trimester combined testing, NIPT and invasive diagnostic testing through chorionic villus sampling or amniocentesis. Furthermore, it contained values clarification exercises encouraging pregnant women to reflect on the potential harms and benefits of having prenatal tests performed. The use of the decision aid improved informed decision-making regarding prenatal testing. Of pregnant women allocated to the intervention group (n=130) 82.3% made an informed choice compared with 66.4% of women in the control group (n=131), P=0.004. As the vast majority of pregnant women made decisions consistent with their attitudes towards having prenatal testing performed, this improvement in informed decision making could be attributed mainly to an increase in decision-relevant knowledge. This study shows that the implementation of a web-based multimedia decision aid directly facilitates the ultimate goal of prenatal testing for fetal chromosomal abnormalities, which is enabling informed autonomous reproductive choice. PMID- 27189021 TI - Multi-ethnic genome-wide association study identifies novel locus for type 2 diabetes susceptibility. AB - Genome-wide association studies (GWAS) have traditionally been undertaken in homogeneous populations from the same ancestry group. However, with the increasing availability of GWAS in large-scale multi-ethnic cohorts, we have evaluated a framework for detecting association of genetic variants with complex traits, allowing for population structure, and developed a powerful test of heterogeneity in allelic effects between ancestry groups. We have applied the methodology to identify and characterise loci associated with susceptibility to type 2 diabetes (T2D) using GWAS data from the Resource for Genetic Epidemiology on Adult Health and Aging, a large multi-ethnic population-based cohort, created for investigating the genetic and environmental basis of age-related diseases. We identified a novel locus for T2D susceptibility at genome-wide significance (P<5 * 10(-8)) that maps to TOMM40-APOE, a region previously implicated in lipid metabolism and Alzheimer's disease. We have also confirmed previous reports that single-nucleotide polymorphisms at the TCF7L2 locus demonstrate the greatest extent of heterogeneity in allelic effects between ethnic groups, with the lowest risk observed in populations of East Asian ancestry. PMID- 27189023 TI - Serotonergic modulation for Dravet Syndrome treatment. PMID- 27189022 TI - A splice variant in the ACSL5 gene relates migraine with fatty acid activation in mitochondria. AB - Genome-wide association studies (GWAS) in migraine are providing the molecular basis of this heterogeneous disease, but the understanding of its aetiology is still incomplete. Although some biomarkers have currently been accepted for migraine, large amount of studies for identifying new ones is needed. The migraine-associated variant rs12355831:A>G (P=2 * 10-6), described in a GWAS of the International Headache Genetic Consortium, is localized in a non-coding sequence with unknown function. We sought to identify the causal variant and the genetic mechanism involved in the migraine risk. To this end, we integrated data of RNA sequences from the Genetic European Variation in Health and Disease (GEUVADIS) and genotypes from 1000 GENOMES of 344 lymphoblastoid cell lines (LCLs), to determine the expression quantitative trait loci (eQTLs) in the region. We found that the migraine-associated variant belongs to a linkage disequilibrium block associated with the expression of an acyl-coenzyme A synthetase 5 (ACSL5) transcript lacking exon 20 (ACSL5-Delta20). We showed by exon-skipping assay a direct causality of rs2256368-G in the exon 20 skipping of approximately 20 to 40% of ACSL5 RNA molecules. In conclusion, we identified the functional variant (rs2256368:A>G) affecting ACSL5 exon 20 skipping, as a causal factor linked to the migraine-associated rs12355831:A>G, suggesting that the activation of long-chain fatty acids by the spliced ACSL5-Delta20 molecules, a mitochondrial located enzyme, is involved in migraine pathology. PMID- 27189024 TI - Fast and accurate prediction of positive and negative urine cultures by flow cytometry. AB - BACKGROUND: Urinary tract infection (UTI) is a widespread infectious disease in humans. Urine culture, a huge workload in the microbiology laboratory, is still the standard diagnostic test for UTI, but most of the cultures are negative. A reliable screening method could reduce unnecessary cultures and quicken reporting of negative results. METHODS: We evaluated the usefulness of a flow cytometry (FC) screening method in the prediction of positive urine culture to reduce the number of urine cultures. The urine specimens sent to the laboratory for culture were tested with the flow cytometer Accuri C6. FC bacterial counts were compared to standard urine culture results to assess the best cut-off values. RESULTS: Two hundred nine urine samples were included, of which 79 (37.8 %) were culture positive. On comparing the culture and the FC data in the ROC curve, the FC bacterial counts of >=10(6) bacteria/mL provided a reliable screening for bacteriuria with a sensitivity and specificity of 99 and 58 %, respectively. All negative FC results (<10(6) bacteria/mL) showed a negative predictive value of 99 % with a negative likelihood ratio of 0.02. The FC bacterial counts of >=10(8)/mL showed a positive predictive value of 99 % with a positive likelihood ratio of 60.9. CONCLUSIONS: Counting bacteria in human urine samples by the FC is a fast, accurate and cost-effective screening method for bacteriuria. Our results showed that FC is able to rule out UTI, which can lead to a substantial reduction (36 %) of urine cultures. It also demonstrated that this method predicts positive cultures accurately. PMID- 27189025 TI - Type 2 diabetes mellitus. AB - Type 2 diabetes mellitus (T2DM) is an expanding global health problem, closely linked to the epidemic of obesity. Individuals with T2DM are at high risk for both microvascular complications (including retinopathy, nephropathy and neuropathy) and macrovascular complications (such as cardiovascular comorbidities), owing to hyperglycaemia and individual components of the insulin resistance (metabolic) syndrome. Environmental factors (for example, obesity, an unhealthy diet and physical inactivity) and genetic factors contribute to the multiple pathophysiological disturbances that are responsible for impaired glucose homeostasis in T2DM. Insulin resistance and impaired insulin secretion remain the core defects in T2DM, but at least six other pathophysiological abnormalities contribute to the dysregulation of glucose metabolism. The multiple pathogenetic disturbances present in T2DM dictate that multiple antidiabetic agents, used in combination, will be required to maintain normoglycaemia. The treatment must not only be effective and safe but also improve the quality of life. Several novel medications are in development, but the greatest need is for agents that enhance insulin sensitivity, halt the progressive pancreatic beta cell failure that is characteristic of T2DM and prevent or reverse the microvascular complications. For an illustrated summary of this Primer, visit: http://go.nature.com/V2eGfN. PMID- 27189026 TI - Treatment of ruptured middle cerebral artery aneurysms by endovascular approach: a single-center experience. AB - PURPOSE: The optimal treatment modalities of ruptured middle cerebral artery aneurysm are still controversial. The objective of this study is to analyze the outcomes of patients with ruptured middle cerebral artery aneurysms treated by endovascular coiling. MATERIALS AND METHODS: From October 2011 to October 2015, 67 patients with 71 ruptured middle cerebral artery aneurysms received endovascular coiling in our hospital. We retrospectively reviewed the clinical, radiologic records and outcomes. RESULTS: Of all the 71 aneurysms (67 patients), 42 were treated by coil embolization merely, 27 by stent-assisted coiling and 2 unruptured aneurysms in patients with bilateral middle cerebral artery aneurysms without receiving treatment. Complete occlusion was achieved in 82.6% (57/69) of all the procedures. Each of incomplete and partial occlusion rates was 8.7% (6/69). Intraoperative rupture of aneurysms occurred in two procedures (2.9%). Thrombogenesis occurred in eight procedures (11.6%). Brain infarction occurred in eight patients (11.9%). Post-operative rebleeding occurred in seven patients (10.4%). Sixty-three patients were followed at a mean follow-up of 8.24 +/- 7.16 months. The mortality and good outcome rate were 3.2% and 90.5%, respectively. Aneurysm recurrence occurred in 6 (13.3%) of the 45 aneurysms at a mean follow-up of 8.44 +/- 7.83 months. CONCLUSIONS: Endovascular coiling is effective for patients with ruptured middle cerebral artery aneurysms. Individualized treatment should be assessed by experienced specialist. It is essential to perform randomized large trials to confirm the efficiency of endovascular coiling. PMID- 27189027 TI - Effects of Antiretroviral Molecules on Survival and Gene Expression of An Osteoblast-like Cell Line. AB - BACKGROUND: The advent of combined antiretroviral therapy effectively undermined the evolution of HIV disease. Nevertheless, clinical observations indicated a clear association between therapy and the impairment of bone mineral density. OBJECTIVE: We selected some antiretroviral compounds used in clinical practice, to study their impact on bone health and their possible implication in the onset of bone disease. METHOD: Scalar concentrations of several antiretroviral drugs (used in single and in combination) were tested on an osteoblast-like cell line, HOBIT cells, to analyse cell survival and gene expression of selected bone markers. RESULTS: None of the tested concentrations of Tenofovir, Emtricitabine, Nevirapine, Maraviroc or Raltegravir induced any significant apoptosis activation at our experimental conditions. Only some protease inhibitors and Efavirenz, at high concentration, determined a significant activation of programmed cell death. In parallel experiments, protease inhibitors used in combination with Tenofovir and Emtricitabine, increased apoptosis. Furthermore, we performed a study of mRNA expression of specific genes involved in osteoblast biology and in bone synthesis and observed that some protease inhibitors induced a selective decrease of some osteogenic markers. CONCLUSION: All the protease inhibitors included in this study trigger apoptosis at the highest concentration analysed, suggesting great caution in HIV-patients co-infected with HBV or HCV, where elevated plasma concentrations of drugs could be reached as a consequence of liver failure. Lastly, an increased apoptosis rate and an impairment of osteogenic markers were recorded only in the presence of Nelfinavir, suggesting a role of protease inhibitors in the alteration of osteoblast biology. PMID- 27189029 TI - Ernest Codman and the end result system: a pioneer of health outcomes revisited. PMID- 27189031 TI - Redox potentials of aryl derivatives from hybrid functional based first principles molecular dynamics. AB - We report the redox potentials of a set of organic aryl molecules, including quinones, juglone, tyrosine and tryptophan, calculated using a first principles molecular dynamics (FPMD) based method. The hybrid functional HSE06 reproduces the redox potentials spanning from -0.25 V to 1.15 V within an error of 0.2 V, whereas the errors with the BLYP functional are much larger (up to 0.7 V). It is found that the BLYP functional predicts consistently lower electron affinities/ionization potentials than HSE06 both in gas phase and in an aqueous solution. In water, the ionization potentials are significantly underestimated by BLYP due to the exaggeration of the mixing between the solute states and the valence band states of liquid water. Hybrid HSE06 markedly improves both the solute levels and water band positions, leading to accurate redox potentials. This study suggests that the current FPMD based method at the level of hybrid functionals is able to accurately compute the redox potentials of a wide spectrum of organic molecules. PMID- 27189028 TI - Perfusion Pressure Cerebral Infarct (PPCI) trial - the importance of mean arterial pressure during cardiopulmonary bypass to prevent cerebral complications after cardiac surgery: study protocol for a randomised controlled trial. AB - BACKGROUND: Debilitating brain injury occurs in 1.6-5 % of patients undergoing cardiac surgery with cardiopulmonary bypass. Diffusion-weighted magnetic resonance imaging studies have reported stroke-like lesions in up to 51 % of patients after cardiac surgery. The majority of the lesions seem to be caused by emboli, but inadequate blood flow caused by other mechanisms may increase ischaemia in the penumbra or cause watershed infarcts. During cardiopulmonary bypass, blood pressure can be below the lower limit of cerebral autoregulation. Although much debated, the constant blood flow provided by the cardiopulmonary bypass system is still considered by many as appropriate to avoid cerebral ischaemia despite the low blood pressure. METHODS/DESIGN: The Perfusion Pressure Cerebral Infarct trial is a single-centre superiority trial with a blinded outcome assessment. The trial is randomising 210 patients with coronary vessel and/or valve disease and who are undergoing cardiac surgery with the use of cardiopulmonary bypass. Patients are stratified by age and surgical procedure and are randomised 1:1 to either an increased mean arterial pressure (70-80 mmHg) or 'usual practice' (40-50 mmHg) during cardiopulmonary bypass. The cardiopulmonary bypass pump flow is fixed and set at 2.4 L/minute/m(2) body surface area plus 10 20 % in both groups. The primary outcome measure is the volume of the new ischaemic cerebral lesions (in mL), expressed as the difference between a baseline, diffusion-weighted, magnetic resonance imaging scan and an equal scan conducted 3-6 days postoperatively. Secondary endpoints are the total number of new ischaemic cerebral lesions, postoperative cognitive dysfunction at discharge and 3 months postoperatively, diffuse cerebral injury evaluated by magnetic resonance spectroscopy and selected biochemical markers of cerebral injury. The sample size will enable us to detect a 50 % reduction in the primary outcome measure in the intervention compared to the control group at a significance level of 0.05 and with a power of 0.80. DISCUSSION: This is the first clinical randomised study to evaluate whether the mean arterial pressure level during cardiopulmonary bypass influences the development of brain injuries that are detected by diffusion-weighted magnetic resonance imaging. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02185885 . Registered on 7 July 2014. PMID- 27189032 TI - The emergence of benchtop NMR systems and the exciting future of the technology. PMID- 27189033 TI - Determination of Clinical Outcome in Mitral Regurgitation With Cardiovascular Magnetic Resonance Quantification. AB - BACKGROUND: Surgery for severe mitral regurgitation is indicated if symptoms or left ventricular dilation or dysfunction occur. However, prognosis is already reduced by this stage, and earlier surgery on asymptomatic patients has been advocated if valve repair is likely, but identifying suitable patients for early surgery is difficult. Quantifying the regurgitation may help, but evidence for its link with outcome is limited. Cardiovascular magnetic resonance (CMR) can accurately quantify mitral regurgitation, and we examined whether this was associated with the future need for surgery. METHODS AND RESULTS: One hundred nine asymptomatic patients with echocardiographic moderate or severe mitral regurgitation had baseline CMR scans and were followed up for up to 8 years (mean, 2.5+/-1.9 years). CMR quantification accurately identified patients who progressed to symptoms or other indications for surgery: 91% of subjects with regurgitant volume <=55 mL survived to 5 years without surgery compared with only 21% with regurgitant volume >55 mL (P<0.0001). A similar separation was observed for regurgitant fraction <=40% and >40%. CMR-derived end-diastolic volume index showed a weaker association with outcome (proportions surviving without surgery at 5 years, 90% for left ventricular end-diastolic volume index <100 mL/m(2) versus 48% for >=100 mL/m(2)) and added little to the discriminatory power of regurgitant fraction/volume alone. CONCLUSIONS: CMR quantification of mitral regurgitation was associated with the development of symptoms or other indications for surgery and showed better discriminatory ability than the reference-standard CMR-derived ventricular volumes. CMR may be able to identify appropriate patients for early surgery, with the potential to change clinical practice, although the clinical benefits of early surgery require confirmation in a clinical trial. PMID- 27189034 TI - Synthesis, structural and electrochemical properties of sodium nickel phosphate for energy storage devices. AB - Electrochemical energy production and storage at large scale and low cost, is a critical bottleneck in renewable energy systems. Oxides and lithium transition metal phosphates have been researched for over two decades and many technologies based on them exist. Much less work has been done investigating the use of sodium phosphates for energy storage. In this work, the synthesis of sodium nickel phosphate at different temperatures is performed and its performance evaluated for supercapacitor applications. The electronic properties of polycrystalline NaNiPO4 polymorphs, triphylite and maricite, t- and m-NaNiPO4 are calculated by means of first-principle calculations based on spin-polarized Density Functional Theory (DFT). The structure and morphology of the polymorphs were characterized and validated experimentally and it is shown that the sodium nickel phosphate (NaNiPO4) exists in two different forms (triphylite and maricite), depending on the synthetic temperature (300-550 degrees C). The as-prepared and triphylite forms of NaNiPO4vs. activated carbon in 2 M NaOH exhibit the maximum specific capacitance of 125 F g(-1) and 85 F g(-1) respectively, at 1 A g(-1); both having excellent cycling stability with retention of 99% capacity up to 2000 cycles. The maricite form showed 70 F g(-1) with a significant drop in capacity after just 50 cycles. These results reveal that the synthesized triphylite showed a high performance energy density of 44 Wh kg(-1) which is attributed to the hierarchical structure of the porous NaNiPO4 nanosheets. At a higher temperature (>400 degrees C) the maricite form of NaNiPO4 possesses a nanoplate-like (coarse and blocky) structure with a large skewing at the intermediate frequency that is not tolerant of cycling. Computed results for the sodium nickel phosphate polymorphs and the electrochemical experimental results are in good agreement. PMID- 27189035 TI - The signaling mechanisms of hippocampal endoplasmic reticulum stress affecting neuronal plasticity-related protein levels in high fat diet-induced obese rats and the regulation of aerobic exercise. AB - High fat diet (HFD)-induced obesity has been shown to reduce the levels of neuronal plasticity-related proteins, specifically brain-derived neurotrophic factor (BDNF) and synaptophysin (SYN), in the hippocampus. However, the underlying mechanisms are not fully clear. Endoplasmic reticulum stress (ERS) has been reported to play a key role in regulating gene expression and protein production by affecting stress signaling pathways and ER functions of protein folding and post-translational modification in peripheral tissues of obese rodent models. Additionally, HFD that is associated with hyperglycemia could induce hippocampal ERS, thus impairing insulin signaling and cognitive health in HFD mice. One goal of this study was to determine whether hyperglycemia and hyperlipidemia could cause hippocampal ERS in HFD-induced obese SD rats, and explore the potential mechanisms of ERS regulating hippocampal BDNF and SYN proteins production. Additionally, although regular aerobic exercise could reduce central inflammation and elevate hippocampal BDNF and SYN levels in obese rats, the regulated mechanisms are poorly understood. Nrf2-HO-1 pathways play roles in anti-ERS, anti-inflammation and anti-apoptosis in peripheral tissues. Therefore, the other goal of this study was to determine whether aerobic exercise could activate Nrf2-HO-1 in hippocampus to alleviate obesity-induced hippocampal ERS, which would lead to increased BDNF and SYN levels. Male SD rats were fed on HFD for 8weeks to establish the obese model. Then, 8weeks of aerobic exercise treadmill intervention was arranged for the obese rats. Results showed that HFD induced obesity caused hyperglycemia and hyperlipidemia, and significantly promoted hippocampal glucose transporter 3 (GLUT3) and fatty acid transport protein 1 (FATP1) protein expression. These results were associated with the activation of hippocampal ERS and ERS-mediated apoptosis. At the same time, we found that excessive hippocampal ERS not only significantly decreased proBDNF-the precursor of mature BDNF, but also attenuated p38/ERK-CREB signaling pathways and activated NLRP3-IL-1beta pathways in obese rats. These results were associated with reduced BDNF and SYN protein production. However, these adverse changes were obviously reversed by aerobic exercise intervention through activating the Nrf2 HO-1 pathways. These results suggest that dietary obesity could induce hippocampal ERS in male SD rats, and excessive hippocampal ERS plays a critical role in decreasing the levels of BDNF and SYN. Moreover, aerobic exercise could activate hippocampal Nrf2 and HO-1 to relieve ERS and heighten BDNF and SYN production in obese rats. PMID- 27189036 TI - In vivo administration of extracellular cGMP normalizes TNF-alpha and membrane expression of AMPA receptors in hippocampus and spatial reference memory but not IL-1beta, NMDA receptors in membrane and working memory in hyperammonemic rats. AB - Patients with hepatic encephalopathy (HE) show working memory and visuo-spatial orientation deficits. Hyperammonemia is a main contributor to cognitive impairment in HE. Hyperammonemic rats show impaired spatial learning and learning ability in the Y maze. Intracerebral administration of extracellular cGMP restores learning in the Y-maze. The underlying mechanisms remain unknown. It also remains unknown whether extracellular cGMP improves neuroinflammation or restores spatial learning in hyperammonemic rats and if it affects differently reference and working memory. The aims of this work were: Spatial working and reference memory were assessed using the radial and Morris water mazes and neuroinflammation by immunohistochemistry and Western blot. Membrane expression of NMDA and AMPA receptor subunits was analyzed using the BS3 crosslinker. Extracellular cGMP was administered intracerebrally using osmotic minipumps. Chronic hyperammonemia induces neuroinflammation in hippocampus, with astrocytes activation and increased IL-1beta, which are associated with increased NMDA receptors membrane expression and impaired working memory. This process is not affected by extracellular cGMP. Hyperammonemia also activates microglia and increases TNF-alpha, alters membrane expression of AMPA receptor subunits (increased GluA1 and reduced GluA2) and impairs reference memory. All these changes are reversed by extracellular cGMP. These results show that extracellular cGMP modulates spatial reference memory but not working memory. This would be mediated by modulation of TNF-alpha levels and of membrane expression of GluA1 and GluA2 subunits of AMPA receptors. PMID- 27189037 TI - Behavioral assessment of neuropathic pain, fatigue, and anxiety in experimental autoimmune encephalomyelitis (EAE) and attenuation by interleukin-10 gene therapy. AB - Relapsing-remitting multiple sclerosis is commonly associated with motor impairments, neuropathic pain, fatigue, mood disorders, and decreased life expectancy. However, preclinical pharmacological studies predominantly rely on clinical scoring of motor deficit as the sole behavioral endpoint. Thus, the translational potential of these studies is limited. Here, we have assessed the therapeutic potential of a novel anti-inflammatory interleukin-10 (IL-10) non viral gene therapy formulation (XT-101-R) in a rat relapsing remitting experimental autoimmune encephalomyelitis (EAE) model. EAE induced motor deficits and neuropathic pain as reflected by induction of low-threshold mechanical allodynia, suppressed voluntary wheel running, decreased social exploration, and was associated with markedly enhanced mortality. We also noted that voluntary wheel running was depressed prior to the onset of motor deficit, and may therefore serve as a predictor of clinical symptoms onset. XT-101-R was intrathecally dosed only once at the onset of motor deficits, and attenuated each of the EAE-induced symptoms and improved survival, relative to vehicle control. This is the first pharmacological assessment of such a broad range of EAE symptoms, and provides support for IL-10 gene therapy as a clinical strategy for the treatment of multiple sclerosis. PMID- 27189039 TI - Computational quantum-classical boundary of noisy commuting quantum circuits. AB - It is often said that the transition from quantum to classical worlds is caused by decoherence originated from an interaction between a system of interest and its surrounding environment. Here we establish a computational quantum-classical boundary from the viewpoint of classical simulatability of a quantum system under decoherence. Specifically, we consider commuting quantum circuits being subject to decoherence. Or equivalently, we can regard them as measurement-based quantum computation on decohered weighted graph states. To show intractability of classical simulation in the quantum side, we utilize the postselection argument and crucially strengthen it by taking noise effect into account. Classical simulatability in the classical side is also shown constructively by using both separable criteria in a projected-entangled-pair-state picture and the Gottesman Knill theorem for mixed state Clifford circuits. We found that when each qubit is subject to a single-qubit complete-positive-trace-preserving noise, the computational quantum-classical boundary is sharply given by the noise rate required for the distillability of a magic state. The obtained quantum-classical boundary of noisy quantum dynamics reveals a complexity landscape of controlled quantum systems. This paves a way to an experimentally feasible verification of quantum mechanics in a high complexity limit beyond classically simulatable region. PMID- 27189038 TI - The effect of daily zinc and/or multivitamin supplements on early childhood development in Tanzania: results from a randomized controlled trial. AB - Impaired childhood development has lifelong consequences for educational attainment and wage-earning potential. Micronutrient supplements have the potential to improve development. The objective of this study was to determine the effect of daily zinc and/or multivitamin (vitamins C, E and B-complex) supplements on development among Tanzanian infants. In this randomized, 2 * 2 factorial, double-blind trial, 2400 infants were randomized to zinc (Zn), multivitamins (MV), zinc and multivitamins (Zn + MV) or placebo at 6 weeks of age. At approximately 15 months, a sub-sample of 247 children underwent developmental assessment using the cognitive, language (receptive and expressive) and motor (fine and gross) scales of the Bayley Scales of Infant and Toddler Development Third Edition (BSID-III). Mean BSID-III scores were compared using univariate and multivariate linear regression models adjusted for child's sex, post-conceptual age and test administrator. Logistic regressions were used to assess odds of low developmental scores. We did not detect a significant difference in mean BSID-III scores in any of the five domains in univariate or multivariate models comparing each of the four treatment groups. We also did not detect a significant difference in mean BSID-III scores when comparing children who received zinc supplements versus those who did not, or in comparisons of children who received multivitamin supplements versus those who did not. There was no significant difference in odds of a low BSID-III score in any of the five domains in treatment arms either. Because neither daily zinc nor multivitamin (vitamins B-complex, C and E) supplementation led to improvements in any of the developmental domains assessed using the BSID-III, we recommend pursuing alternative interventions to promote early childhood development in vulnerable populations. (c) 2016 John Wiley & Sons Ltd. PMID- 27189040 TI - Post-traumatic stress disorder. AB - Post-traumatic stress disorder (PTSD) occurs in 5-10% of the population and is twice as common in women as in men. Although trauma exposure is the precipitating event for PTSD to develop, biological and psychosocial risk factors are increasingly viewed as predictors of symptom onset, severity and chronicity. PTSD affects multiple biological systems, such as brain circuitry and neurochemistry, and cellular, immune, endocrine and metabolic function. Treatment approaches involve a combination of medications and psychotherapy, with psychotherapy overall showing greatest efficacy. Studies of PTSD pathophysiology initially focused on the psychophysiology and neurobiology of stress responses, and the acquisition and the extinction of fear memories. However, increasing emphasis is being placed on identifying factors that explain individual differences in responses to trauma and promotion of resilience, such as genetic and social factors, brain developmental processes, cumulative biological and psychological effects of early childhood and other stressful lifetime events. The field of PTSD is currently challenged by fluctuations in diagnostic criteria, which have implications for epidemiological, biological, genetic and treatment studies. However, the advent of new biological methodologies offers the possibility of large-scale approaches to heterogeneous and genetically complex brain disorders, and provides optimism that individualized approaches to diagnosis and treatment will be discovered. PMID- 27189041 TI - Porcine epidemic diarrhea virus: An overview of current virological and serological diagnostic methods. AB - Porcine epidemic diarrhea virus (PEDV) is the causative agent of an acute, highly contagious, and severe enteric disease that leads to high mortality rates in suckling piglets. Therefore, accurate diagnosis of PEDV infection is critical for the implementation of control measures for the virus. Many diagnostic tests have been recently developed and are currently available for the detection of PEDV, its proteins or nucleic acid, including virus isolation, immunofluorescence (IF) or immunohistochemistry (IHC), polymerase chain reaction (PCR) and isothermal amplification assays. Additionally, several serological assays have been developed and are currently used for the detection of antibodies against PEDV. Molecular assays such as real-time reverse transcriptase-PCR (rRT-PCR) became the methods of choice for the diagnosis of PEDV infection, providing sensitive, specific and rapid detection of the virus RNA in clinical samples. Whereas serological assays have been widely used to monitor prior exposure to the virus and to evaluate the efficacy of novel vaccine candidates or vaccination strategies. Here we discuss the properties of current PEDV diagnostic assays and prospects for improving diagnostic strategies in the future. PMID- 27189042 TI - Characterization of codon usage pattern and influencing factors in Japanese encephalitis virus. AB - Recently, several outbreaks of Japanese encephalitis (JE), caused by Japanese encephalitis virus (JEV), have been reported and it has become cause of concern across the world. In this study, detailed analysis of JEV codon usage pattern was performed. The relative synonymous codon usage (RSCU) values along with mean effective number of codons (ENC) value of 55.30 indicated the presence of low codon usages bias in JEV. The effect of mutational pressure on codon usage bias was confirmed by significant correlations of A3s, U3s, G3s, C3s, GC3s, ENC values, with overall nucleotide contents (A%, U%, G%, C%, and GC%). The correlation analysis of A3s, U3s, G3s, C3s, GC3s, with axis values of correspondence analysis (CoA) further confirmed the role of mutational pressure. However, the correlation analysis of Gravy values and Aroma values with A3s, U3s, G3s, C3s, and GC3s, indicated the presence of natural selection on codon usage bias in addition to mutational pressure. The natural selection was further confirmed by codon adaptation index (CAI) analysis. Additionally, relative dinucleotide frequencies, geographical distribution, and evolutionary processes also influenced the codon usage pattern to some extent. PMID- 27189043 TI - First Production of Larvae Using Cryopreserved Sperm: Effects of Preservation Temperature and Cryopreservation on European Eel Sperm Fertilization Capacity. AB - Sperm cryopreservation is a useful tool in captive fish reproduction management, that is to synchronize gamete production, especially in the case of species as the European eel, where the time of female spawning readiness is unpredictable. Several protocols to cryopreserve sperm of this species have been described, but until recently fertilization trials were not feasible. This study evaluated the effect of cold storage of diluted sperm prior to fertilizations and tested whether a previously defined protocol for European eel sperm cryopreservation can be successfully applied in fertilization trials to produce viable offspring. In our experiment, the sperm motility was evaluated after the extraction and the best samples were selected and pooled. Until stripping of eggs and fertilization, diluted sperm samples were maintained at either 4 or 20 degrees C, or cryopreserved, following existing protocols. Fertilization of two egg batches was attempted. Diluted sperm caused a similar percentage of fertilized eggs and a similar number of embryos and larvae, independently of storage temperature (4 or 20 degrees C). The cryopreserved sperm resulted in a lower percentage of fertilized eggs, but embryos developed and a few larvae ('cryolarvae') were obtained 55 h after fertilization in one of the two egg batches. This result evidences that the tested cryopreservation protocol is applicable for eel reproduction management, although improvements will be required to enhance fertilization success. PMID- 27189044 TI - Prevalence and features of chronic viral hepatitis and HIV coinfection in Italian prisons. PMID- 27189045 TI - Analysis of serum immune markers in seropositive and seronegative rheumatoid arthritis and in high-risk seropositive arthralgia patients. AB - Presence of autoantibodies precedes development of seropositive rheumatoid arthritis (SP RA) and seropositive arthralgia patients (SAP) are at risk of developing RA. The aims of the study are to identify additional serum immune markers discriminating between SP and seronegative (SN) RA, and markers identifying high-risk SAP. Sera from SAP (n = 27), SP RA (n = 22), SN RA (n = 11) and healthy controls (n = 20) were analyzed using the Human Cytokine 25-Plex Panel. Selected markers were validated in independent cohorts of SP RA (n = 35) and SN RA (n = 12) patients. Eleven of 27 SAP developed RA within 8 months (median follow-up time, range 1-32 months), and their baseline serum markers were compared to 16 non-progressing SAP. SAP and SP RA patients showed a marked overlap in their systemic immune profiles, while SN RA showed a distinct immune profile. Three of 4 markers discriminating between SP and SN RA (IL-1beta, IL-15 and Eotaxin, but not CCL5) were similarly modulated in independent cohorts. SAP progressing to RA showed trends for increases in IL-5, MIP-1beta, IL-1RA and IL 12 compared to non-progressing SAP. ROC analysis showed that serum IL-5 most accurately discriminated between the two SAP groups (AUC > 0.8), suggesting that baseline IL-5 levels may aid the identification of high-risk SAP. PMID- 27189047 TI - An ecological analysis of prison overcrowding and suicide rates in England and Wales, 2000-2014. AB - Prisoners are at a greatly increased risk of suicides compared to the general population. Differences in suicide risk can be partly explained by individual risk factors, but the contribution of prison characteristics remains unclear. Overcrowded prisons have higher suicide rates, but this may be related to prison function, security level, population size and turnover. The aim of the current study was to investigate the contribution of each of these prison characteristics to suicide rates, using data from the Ministry of Justice for adult prisons in England and Wales from 2000 to 2014. Negative binomial regression analysis showed that larger population size, higher turnover, higher security and public management were associated with higher suicide rates. When controlling for these factors, overcrowding was not found to be related to suicide rates. Questions remain about the causal mechanisms underlying variation in prison suicides and the impact of the lived experience of overcrowding. Further research is needed to examine the relative contribution of prison and prisoner characteristics to suicides. PMID- 27189046 TI - Impact of Implementing a Wiki to Develop Structured Electronic Order Sets on Physicians' Intention to Use Wiki-Based Order Sets. AB - BACKGROUND: Wikis have the potential to promote best practices in health systems by sharing order sets with a broad community of stakeholders. However, little is known about the impact of using a wiki on clinicians' intention to use wiki-based order sets. OBJECTIVE: The aims of this study were: (1) to describe the use of a wiki to create structured order sets for a single emergency department; (2) to evaluate whether the use of this wiki changed emergency physicians' future intention to use wiki-based order sets; and (3) to understand the impact of using the wiki on the behavioral determinants for using wiki-based order sets. METHODS: This was a pre/post-intervention mixed-methods study conducted in one hospital in Levis, Quebec. The intervention was comprised of receiving access to and being motivated by the department head to use a wiki for 6 months to create electronic order sets designed to be used in a computer physician order entry system. Before and after our intervention, we asked participants to complete a previously validated questionnaire based on the Theory of Planned Behavior. Our primary outcome was the intention to use wiki-based order sets in clinical practice. We also assessed participants' attitude, perceived behavioral control, and subjective norm to use wiki-based order sets. Paired pre- and post-Likert scores were compared using Wilcoxon signed-rank tests. The post-questionnaire also included open-ended questions concerning participants' comments about the wiki, which were then classified into themes using an existing taxonomy. RESULTS: Twenty-eight emergency physicians were enrolled in the study (response rate: 100%). Physicians' mean intention to use a wiki-based reminder was 5.42 (SD 1.04) before the intervention, and increased to 5.81 (SD 1.25) on a 7-point Likert scale (P =.03) after the intervention. Participants' attitude towards using a wiki-based order set also increased from 5.07 (SD 0.90) to 5.57 (SD 0.88) (P =.003). Perceived behavioral control and subjective norm did not change. Easier information sharing was the most frequently positive impact raised. In order of frequency, the three most important facilitators reported were: ease of use, support from colleagues, and promotion by the departmental head. Although participants did not mention any perceived negative impacts, they raised the following barriers in order of frequency: poor organization of information, slow computers, and difficult wiki access. CONCLUSIONS: Emergency physicians' intention and attitude to use wiki-based order sets increased after having access to and being motivated to use a wiki for 6 months. Future studies need to explore if this increased intention will translate into sustained actual use and improve patient care. Certain barriers need to be addressed before implementing a wiki for use on a larger scale. PMID- 27189048 TI - The efficacy of electrical stimulation in experimentally induced cutaneous wounds in animals. AB - BACKGROUND: Complicated cutaneous wounds and their subsequent management can be a clinical challenge in veterinary medicine. There is still an unmet need for an ideal wound healing therapy that is able to stimulate efficiency and quality of repair. Skin wounds generate large and persistent endogenous electric currents and fields termed the "current of injury". The current of injury is involved in numerous processes of wound healing. These observations have led to the hypothesis that applied electrical stimulation (ES) may promote wound healing by imitating the natural electrical current that occurs in cutaneous wounds. OBJECTIVES: This review details the use, effect and mechanism of ES in different preclinical experimental cutaneous wound models and discusses the potential of how ES could be translated into veterinary practice. RESULTS: Studies have found a variable effect of ES on wound healing. Some have been positive with faster rates of wound re-epithelialization, increased wound collagen formation and angiogenesis noted. Other studies have shown no effect or detrimental results. The effects of ES are highly influenced by the ES modality, polarity and parameters. CONCLUSIONS AND CLINICAL IMPORTANCE: Electrical stimulation has the potential to play a significant role in enhancing cutaneous wound healing in veterinary practice. Clinical studies are necessary to corroborate the findings from experimental studies which have shown promise including the use of alternating pulsed and direct current and the use of bio-electric dressings. The ideal ES device would need to be safe, easy to use, portable, noninvasive and aid wound healing by having a beneficial effect on all wound healing stages. PMID- 27189049 TI - Micronutrient Composition of 35 Food Fishes from India and Their Significance in Human Nutrition. AB - The micronutrients (vitamins and minerals) are required in small amounts but are essential for health, development, and growth. Micronutrient deficiencies, which affect over two billion people around the globe, are the leading cause of many ailments including mental retardation, preventable blindness, and death during childbirth. Fish is an important dietary source of micronutrients and plays important role in human nutrition. In the present investigation, micronutrient composition of 35 food fishes (includes both finfishes and shellfishes) was investigated from varying aquatic habitats. Macrominerals (Na, K, Ca, Mg) and trace elements (Fe, Cu, Zn, Mn, Se) were determined by either atomic absorption spectroscopy (AAS) or inductively coupled plasma mass spectrometry (ICP MS)/atomic emission spectrometry (ICP-AES). Phosphorus content was determined either spectrophotometrically or by ICP-AES. Fat-soluble vitamins (A, D, E, K) were analyzed by high-performance liquid chromatography (HPLC). The analysis showed that, in general, the marine fishes were rich in sodium and potassium; small indigenous fishes (SIFs) in calcium, iron, and manganese; coldwater fishes in selenium; and the brackishwater fishes in phosphorous. The marine fishes Sardinella longiceps and Epinephelus spp. and the SIFs were rich in all fat soluble vitamins. All these recommendations were made according to the potential contribution (daily value %) of the species to the recommended daily allowance (RDA). Information on the micronutrients generated would enhance the utility of fish in both community and clinical nutrition. PMID- 27189050 TI - Isolated limb perfusion in Merkel cell carcinoma offers high rate of complete response and durable local-regional control: Systematic review and institutional experience. AB - INTRODUCTION: Hyperthermic isolated limb perfusion (HILP) has an established role in the management of melanoma, but its role for Merkel cell carcinoma (MCC) is less well defined. METHODS: Retrospective review of our institutional experience with HILP for MCC was conducted (2009-2015). Literature search was performed through 04/2015 and 10 studies met inclusion criteria. RESULTS: Four patients underwent HILP for MCC at our institution. There were no major complications and complete response was achieved in all patients. Early metastatic recurrence developed in two patients. The remaining two had no evidence of disease at last follow-up (36 months) or death (39 months). Systematic review identified an additional 12 pts that underwent HILP for MCC, for a total of 16 cases. Median age was 73 [IQR 69-78] years and 56% were men. Of the patients with reported follow-up, 12 (86%) had complete response, 1 had stable disease, and 1 partial response. Four patients developed local-regional recurrence and six distant metastases, all within 6 months. Overall median follow-up time was 15 [7-36] months. CONCLUSION: Among a highly selective group of patients, regional perfusion for MCC is safe and has a high complete response rate. HILP is an acceptable therapeutic modality for obtaining durable loco-regional control but early distant metastatic disease remains a significant cause of mortality. J. Surg. Oncol. 2016;114:187-192. (c) 2016 Wiley Periodicals, Inc. PMID- 27189052 TI - Secondary Treatment of Local Bleeding in Patients Undergoing Hepatic Resection: In reply to Sugimachi. PMID- 27189051 TI - Topical Delivery of Protein and Peptide Using Novel Cell Penetrating Peptide IMT P8. AB - Skin, being the largest organ of the body, is an important site for drug administration. However, most of the drugs have poor permeability and thus drug delivery through the skin is very challenging. In this study, we examined the transdermal delivery capability of IMT-P8, a novel cell-penetrating peptide. We generated IMT-P8-GFP and IMT-P8-KLA fusion constructs and evaluated their internalization into mouse skin after topical application. Our results demonstrate that IMT-P8 is capable of transporting green fluorescent protein (GFP) and proapoptotic peptide, KLA into the skin and also in different cell lines. Interestingly, uptake of IMT-P8-GFP was considerably higher than TAT-GFP in HeLa cells. After internalization, IMT-P8-KLA got localized to the mitochondria and caused significant cell death in HeLa cells signifying an intact biological activity. Further in vivo skin penetration experiments revealed that after topical application, IMT-P8 penetrated the stratum corneum, entered into the viable epidermis and accumulated inside the hair follicles. In addition, both IMT-P8-KLA and IMT-P8-GFP internalized into the hair follicles and dermal tissue of the skin following topical application. These results suggested that IMT-P8 could be a potential candidate to be used as a topical delivery vehicle for various cosmetic and skin disease applications. PMID- 27189053 TI - Correlation of normal-range FMR1 repeat length or genotypes and reproductive parameters. AB - PURPOSE: This study aims to ascertain whether the length of normal-ranged CGG repeats on the FMR1 gene correlates with abnormal reproductive parameters. METHODS: We performed a retrospective, cross-sectional study of all FMR1 carrier screening performed as part of routine care at a large university-based fertility center from January 2011 to March 2014. Correlations were performed between normal-range FMR1 length and baseline serum anti-Mullerian hormone (AMH), cycle day 3 follicle stimulating hormone (FSH), ovarian volumes (OV), antral follicle counts (AFC), and incidence of diminished ovarian reserve (DOR), while controlling for the effect of age. RESULTS: Six hundred three FMR1 screening results were collected. One subject was found to be a pre-mutation carrier and was excluded from the study. Baseline serum AMH, cycle day 3 FSH, OV, and AFC data were collected for the 602 subjects with normal-ranged CGG repeats. No significant difference in median age was noted amongst any of the FMR1 repeat genotypes. No significant correlation or association was found between any allele length or genotype, with any of the reproductive parameters or with incidence of DOR at any age (p > 0.05). However, subjects who were less than 35 years old with low/low genotype were significantly more likely to have below average AMH levels compared to those with normal/normal genotype (RR 3.82; 95 % CI 1.38-10.56). CONCLUSIONS: This large study did not demonstrate any substantial association between normal-range FMR1 repeat lengths and reproductive parameters. PMID- 27189055 TI - Mitochondrial Dysfunction and Ca2+ Overload in Injured Sertoli Cells Exposed to Bisphenol A. AB - Bisphenol-A (BPA) is well known as one of endocrine-disrupting chemicals and testicular toxicant. In this present study, we determined whether BPA caused cell injury through mitochondria impairment and ROS overproduction. The cellular ROS production, mitochondrial ATP synthetase activity and Ca2+ concentration were examined. We have found BPA caused the cellular mitochondria dysfunction and followed by cell death in Sertoli cells. Moreover cytoplasm Ca2+ overload was also involved. Furthermore, pretreatment with N-acetyl-L-cysteine (NAC) could alleviate the damage by causing a remarkable decrease in ROS production and mitochondrial dysfunction. Collectively, our results showed that BPA exposure induced Sertoli cell apoptosis because of excessive ROS generation and mitochondrial dysfunction. (c) 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 823-831, 2017. PMID- 27189054 TI - Effect of acteoside on the re-localization and abnormal morphology of mitochondria in porcine oocytes during in vitro maturation. AB - PURPOSE: The aim of this study is to investigate the effect of acteoside, an antioxidant, on in vitro maturation (IVM) of oocytes to improve early parthenogenetic embryonic developmental competence. METHODS: Porcine immature oocytes (total 770) were cultured in IVM medium with acteoside at various concentrations, 0 (control), 10, 30, and 50 MUM. Each group was assessed for maturation and subsequent development rates, reactive oxygen species (ROS) level (15 oocytes per group and four independent experiments performed), ultrastructure observation (15 oocytes per group), mitochondrial activity (30 oocytes per groups and three independent experiments performed), and expression patterns of apoptosis-related genes (100 expended parthenogenetic embryos per group and three independent experiment performed). Main outcome measures were the rates of IVM, blastocyst formation, ROS, mitochondria, and expression of apoptosis-related genes in oocytes treated with acteoside. RESULT(S): Addition of acteoside during IVM did not change the maturation efficiency of oocytes but improved the rate of blastocyst formation with significantly decreased ROS level. Moreover, in acteoside-treated oocytes, cytoplasmic maturation was improved with morphologically uniform distribution of mitochondria and lipid droplets in cytoplasm. Acteoside supplementation also increased the mRNA expression levels of antiapoptotic genes and reduced those of pro-apoptotic genes. CONCLUSION(S): Acteoside supplementation in IVM medium improves the oocyte quality and subsequent development of pre-implantation embryos that would eventually contribute to produce embryos with high embryonic development competence. PMID- 27189056 TI - Post-transplant lymphoproliferative disorders. AB - Post-transplant lymphoproliferative disorders (PTLDs) are a group of conditions that involve uncontrolled proliferation of lymphoid cells as a consequence of extrinsic immunosuppression after organ or haematopoietic stem cell transplant. PTLDs show some similarities to classic lymphomas in the non-immunosuppressed general population. The oncogenic Epstein-Barr virus (EBV) is a key pathogenic driver in many early-onset cases, through multiple mechanisms. The incidence of PTLD varies with the type of transplant; a clear distinction should therefore be made between the conditions after solid organ transplant and after haematopoietic stem cell transplant. Recipient EBV seronegativity and the intensity of immunosuppression are among key risk factors. Symptoms and signs depend on the localization of the lymphoid masses. Diagnosis requires histopathology, although imaging techniques can provide additional supportive evidence. Pre-emptive intervention based on monitoring EBV levels in blood has emerged as the preferred strategy for PTLD prevention. Treatment of established disease includes reduction of immunosuppression and/or administration of rituximab (a B cell-specific antibody against CD20), chemotherapy and EBV-specific cytotoxic T cells. Despite these strategies, the mortality and morbidity remains considerable. Patient outcome is influenced by the severity of presentation, treatment-related complications and risk of allograft loss. New innovative treatment options hold promise for changing the outlook in the future. PMID- 27189057 TI - Als1 and Als3 regulate the intracellular uptake of copper ions when Candida albicans biofilms are exposed to metallic copper surfaces. AB - Copper surfaces possess efficient antimicrobial effect. Here, we reported that copper surfaces could inactivate Candida albicans biofilms within 40 min. The intracellular reactive oxygen species in C. albicans biofilms were immediately stimulated during the contact of copper surfaces, which might be an important factor for killing the mature biofilms. Copper release assay demonstrated that the copper ions automatically released from the surface of 1 mm thick copper coupons with over 99.9% purity are not the key determinant for the copper mediated killing action. The susceptibility test to copper surfaces by using C. albicans mutant strains, which were involved in efflux pumps, adhesins, biofilms formation or osmotic stress response showed that als1/als1 and als3/als3 displayed higher resistance to the copper surface contact than other mutants did. The intracellular concentration of copper ions was lower in als1/als1 and als3/als3 than that in wild-type strain. Transcriptional analysis revealed that the expression of copper transporter-related gene, CRP1, was significantly increased in als1/als1, als3/als3, suggesting a potential role of ALS1 and ALS3 in absorbing ions by regulating the expression of CRP1 This study provides a potential application in treating pathogenic fungi by using copper surfaces and uncovers the roles of ALS1 and ALS3 in absorbing copper ions for C. albicans. PMID- 27189058 TI - Agarivorans aestuarii sp. nov., an agar-degrading bacterium isolated from a tidal flat. AB - A Gram-reaction-negative, aerobic, non-spore forming, rod-shaped bacterium motile with a single polar flagellum, designated strain hydD622T, was isolated from the sediment of a tidal flat at Asan Bay, Korea. Strain hydD622T exhibited an agarolytic activity. Comparison of 16S rRNA gene sequences revealed that strain hydD622T was closely related to Agarivorans litoreus KCTC 42116T, Agarivorans albus KCTC 22256T and Agarivorans gilvus KCTC 32555T with similarities of 98.4, 98.0 and 96.5 %, respectively. Strain hydD622T was clustered distantly from the other genera in the family Alteromonadaceae but formed a unique clade within the genus Agarivorans based on the 16S rRNA gene sequence. The DNA-DNA relatedness with Agarivorans litoreus KCTC 42116T and Agarivorans. albus KCTC 22256T was 39.0 and 37.8 %, respectively. The major fatty acids (>10 %) were C16 : 0,C16 : 1omega6c/C16 : 1omega7c and C18 : 1omega6c/C18 : 1omega7c. The respiratory quinone was ubiquinone-8, and the polar lipid profile consisted of phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol and an unidentified lipid. The DNA G+C content was 44 mol%. On the basis of physiological, chemotaxonomic and phylogenetic analyses, strain hydD622T represents a novel species within the genus Agarivorans, for which the name Agarivorans aestuarii sp. nov. is proposed. The type strain of Agarivorans aestuarii sp. nov. is hydD622T (=KCTC 32543T=CGMCC 1.12692T). PMID- 27189059 TI - A new multiplex method for the diagnosis of peroxisomal disorders allowing simultaneous determination of plasma very-long-chain fatty acids, phytanic, pristanic, docosahexaenoic and bile acids by high-performance liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry. AB - Peroxisomal disorders (PDs) present with wide phenotypic variability. An appropriate diagnosis requires a complete analysis of peroxisomal metabolites. We developed a multiplex LC-MS/MS method, using atmospheric pressure chemical ionization allowing the simultaneous determination in plasma of very-long-chain fatty acids, phytanic, pristanic, docosahexaenoic acids and di- and tri hydroxycolestanoic bile acids. Two hundred microliters of plasma extracted with acetonitrile and 200MUl extracted with hexane after an acid hydrolysis were combined, evaporated, dissolved in 10MUl of methanol and analyzed. The acquisition was in negative-ion mode using multiple reaction monitoring. The method was validated analytically and clinically. Linearity was 0.1-200MUmol/l for docosanoic, cis-13-docosenoic, tetracosanoic, cis-15-tetracosenoic and phytanic acids; 0.01-10MUmol/l for hexacosanoic acid; 0.02-20MUmol/l for di hydroxycolestanoic, tri-hydroxycolestanoic and pristanic acids; 0.3-300MUmol/l for docosahexaenoic acid. Intra-day and inter-day CVs were below 3.88 and 3.98 respectively for all compounds. Samples from patients with known peroxisomal disorders were compared with controls and the method allowed to confirm the diagnosis in all subjects with a 100% sensitivity. The advantage of this multiplex method is to allow in a single chromatographic run the simultaneous determination of a large number of peroxisome biomarkers with a simple preparative phase without derivatization. PMID- 27189062 TI - Chitinase 3 Like-1: An Emerging Molecule Involved in Diabetes and Diabetic Complications. AB - Chitinase 3 like-1 (CHI3L1) is a chitinase-like protein member of family 18 chitinases, expressed in innate immune cells and involved in endothelial dysfunction and tissue remodelling. Since CHI3L1 is highly expressed in a variety of inflammatory diseases of infectious and non-infectious aetiology, it is recognised as a non-invasive prognostic biomarker for inflammation. A variety of studies revealing the increase in CHI3L1 levels in obesity, insulin resistance and in pathological conditions, such as atherosclerosis, coronary artery disease, acute ischaemic stroke, nephropathy, diabetic retinopathy and osteolytic processes, have suggested that CHI3L1 may also play a critical role in the evolution and complication of diabetes mellitus (DM). In this review we highlight the impact of CHI3L1 expression in DM and its contribution to the complication of this disease. PMID- 27189060 TI - Theobroma cacao L. pathogenesis-related gene tandem array members show diverse expression dynamics in response to pathogen colonization. AB - BACKGROUND: The pathogenesis-related (PR) group of proteins are operationally defined as polypeptides that increase in concentration in plant tissues upon contact with a pathogen. To date, 17 classes of highly divergent proteins have been described that act through multiple mechanisms of pathogen resistance. Characterizing these families in cacao, an economically important tree crop, and comparing the families to those in other species, is an important step in understanding cacao's immune response. RESULTS: Using publically available resources, all members of the 17 recognized pathogenesis-related gene families in the genome of Theobroma cacao were identified and annotated resulting in a set of ~350 members in both published cacao genomes. Approximately 50 % of these genes are organized in tandem arrays scattered throughout the genome. This feature was observed in five additional plant taxa (three dicots and two monocots), suggesting that tandem duplication has played an important role in the evolution of the PR genes in higher plants. Expression profiling captured the dynamics and complexity of PR genes expression at basal levels and after induction by two cacao pathogens (the oomycete, Phytophthora palmivora, and the fungus, Colletotrichum theobromicola), identifying specific genes within families that are more responsive to pathogen challenge. Subsequent qRT-PCR validated the induction of several PR-1, PR-3, PR-4, and PR-10 family members, with greater than 1000 fold induction detected for specific genes. CONCLUSIONS: We describe candidate genes that are likely to be involved in cacao's defense against Phytophthora and Colletotrichum infection and could be potentially useful for marker-assisted selection for breeding of disease resistant cacao varieties. The data presented here, along with existing cacao-omics resources, will enable targeted functional genetic screening of defense genes likely to play critical functions in cacao's defense against its pathogens. PMID- 27189061 TI - Reciprocal activation between STAT3 and miR-181b regulates the proliferation of esophageal cancer stem-like cells via the CYLD pathway. AB - BACKGROUND: Recent studies have suggested that cancer cells contain subpopulations that can initiate tumor growth, self-renew, and maintain tumor cell growth. However, for esophageal cancer cells, the relationship between STAT3, microRNAs and cancer stem cells remains unclear. METHODS: Serum-free culture was used to enrich esophageal cancer stem-like cells (ECSLC). Flow cytometry determined the proportion of ECSLC. qPCR were performed to examine expression level of stemness factors, mesenchymal markers, ATP-binding cassette (ABC) transporters, STAT3, miR-181b, CYLD. Western blot were performed to analyze the expression of STAT3, p-STAT3 and CYLD (cylindromatosis). BALB/c mice xenograft studies were conducted to evaluate the tumorigenicity of enriched ECSLC. Sphere formation assay and colony formation assays were employed to analyze the relationship between STAT3 and miR-181b. Luciferase assays were used to evaluate activity which CYLD is a target of miR-181b. RESULTS: Sphere formation cells (SFCs) with properties of ECSLC were enriched. Enriched SFCs in serum-free suspension culture exhibited cancer stem-like cell properties and increased single-positive CD44 + CD24-, stemness factor, mesenchymal marker expression ABC transporters and tumorigenicity in vivo compared with the parental cells. Additionally, we found that reciprocal activation between STAT3 and miR 181b regulated SFCs proliferation. Moreover, STAT3 directly activated miR-181b transcription in SFCs and miR-181b then potentiated p-STAT3 activity. Luciferase assays indicated that CYLD was a direct and functional target of miR-181b. CONCLUSION: The mutual regulation between STAT3 and miR-181b in SFCs was required for proliferation and apoptosis resistance. STAT3 and miR-181b control each other's expression in a positive feedback loop that regulates SFCs via CYLD pathway. These findings maybe is helpful for targeting ECSLC and providing approach for esophageal cancer treatments. PMID- 27189065 TI - Erratum to: Autophagy is a major regulator of beta cell insulin homeostasis. PMID- 27189063 TI - Combinatorial metabolic engineering of industrial Gluconobacter oxydans DSM2343 for boosting 5-keto-D-gluconic acid accumulation. AB - BACKGROUND: L-(+)-tartaric acid (L-TA) is an important organic acid, which is produced from the cream of tartar or stereospecific hydrolysis of the cis epoxysuccinate. The former method is limited by the availability of raw material and the latter is dependent on the petrochemical material. Thus, new processes for the economical preparation of L-TA from carbohydrate or renewable resource would be much more attractive. Production of 5-keto-D-gluconate (5-KGA) from glucose by Gluconobacter oxydans is the first step to produce L-TA. The aim of this work is to enhance 5-KGA accumulation using combinatorial metabolic engineering strategies in G. oxydans. The sldAB gene, encoding sorbitol dehydrogenase, was overexpressed in an industrial strain G. oxydans ZJU2 under a carefully selected promoter, P0169. To enhance the efficiency of the oxidation by sldAB, the coenzyme pyrroloquinoline quinone (PQQ) and respiratory chain were engineered. Besides, the role in sldAB overexpression, coenzyme and respiratory chain engineering and their subsequent effects on 5-KGA production were investigated. RESULTS: An efficient, stable recombinant strain was constructed, whereas the 5-KGA production could be enhanced. By self-overexpressing the sldAB gene in G. oxydans ZJU2 under the constitutive promoter P0169, the resulting strain, G. oxydans ZJU3, produced 122.48 +/- 0.41 g/L of 5-KGA. Furthermore, through the coenzyme and respiratory chain engineering, the titer and productivity of 5-KGA reached 144.52 +/- 2.94 g/L and 2.26 g/(L . h), respectively, in a 15 L fermenter. It could be further improved the 5-KGA titer by 12.10 % through the fed-batch fermentation under the pH shift and dissolved oxygen tension (DOT) control condition, obtained 162 +/- 2.12 g/L with the productivity of 2.53 g/(L . h) within 64 h. CONCLUSIONS: The 5-KGA production could be significantly enhanced with the combinatorial metabolic engineering strategy in Gluconobacter strain, including sldAB overexpression, coenzyme and respiratory chain engineering. Fed-batch fermentation could further enlarge the positive effect and increase the 5-KGA production. All of these demonstrated that the robust recombinant strain can efficiently produce 5-KGA in larger scale to fulfill the industrial production of L-TA from 5-KGA. PMID- 27189064 TI - Genetic sequence data reveals widespread sharing of Leucocytozoon lineages in corvids. AB - Leucocytozoon, a widespread hemosporidian blood parasite that infects a broad group of avian families, has been studied in corvids (family: Corvidae) for over a century. Current taxonomic classification indicates that Leucocytozoon sakharoffi infects crows and related Corvus spp., while Leucocytozoon berestneffi infects magpies (Pica spp.) and blue jays (Cyanocitta sp.). This intrafamily host specificity was based on the experimental transmissibility of the parasites, as well as slight differences in their morphology and life cycle development. Genetic sequence data from Leucocytozoon spp. infecting corvids is scarce, and until the present study, sequence data has not been analyzed to confirm the current taxonomic distinctions. Here, we predict the phylogenetic relationships of Leucocytozoon cytochrome b lineages recovered from infected American Crows (Corvus brachyrhynchos), yellow-billed magpies (Pica nuttalli), and Steller's jays (Cyanocitta stelleri) to explore the host specificity pattern of L. sakharoffi and L. berestneffi. Phylogenetic reconstruction revealed a single large clade containing nearly every lineage recovered from the three host species, while showing no evidence of the expected distinction between L. sakharoffi and L. berestneffi. In addition, five of the detected lineages were recovered from both crows and magpies. This absence of the previously described host specificity in corvid Leucocytozoon spp. suggests that L. sakharoffi and L. berestneffi be reexamined from a taxonomic perspective. PMID- 27189067 TI - Incidence, prevalence and mortality of type 2 diabetes requiring glucose-lowering treatment, and associated risks of cardiovascular complications: a nationwide study in Sweden, 2006-2013. AB - AIMS/HYPOTHESIS: The global diabetes epidemic affects countries differently. We aimed to describe trends in the incidence and prevalence of type 2 diabetes mellitus requiring glucose-lowering treatment, together with associated life expectancy and risks of significant clinical complications. METHODS: Data on patients with type 2 diabetes who filled a prescription for any glucose-lowering drug (GLD) during the period 2006-2013 were extracted from the Swedish Prescribed Drug Register, Cause of Death Register and Swedish National Patient Register. RESULTS: In 2013, the prevalence of GLD-treated type 2 diabetes was 4.4% (n = 352,436) and the incidence was 399 per 100,000 population (n = 30,620). During 2006-2013, the prevalence increased by 61% while the incidence remained relatively stable; the prevalence of cardiovascular disease (CVD, 34% in 2013) and microvascular disease (16% in 2013) was also stable. Insulin use increased by 29% while sulfonylurea use declined by 55%. Compared with the general population, patients with type 2 diabetes had increased risk of myocardial infarction, stroke and all-cause mortality, with age-standardised risks of ~1.7-, 1.5- and 1.3-fold, respectively. These risks declined over time. Life-years lost due to diabetes was most pronounced at younger ages and improved in women over time from 2006 to 2013. CONCLUSIONS/INTERPRETATION: The prevalence of type 2 diabetes requiring GLD treatment in Sweden increased substantially in recent years, while the incidence remained stable. Use of sulfonylurea declined while insulin use increased. The high prevalence of diabetes-related comorbidities, increased risk of complications and life-years lost highlights the need for optimised and new preventive strategies in patients with type 2 diabetes. PMID- 27189066 TI - Diabetes, prostate cancer screening and risk of low- and high-grade prostate cancer: an 11 year historical population follow-up study of more than 1 million men. AB - AIMS/HYPOTHESIS: An inverse association has consistently been shown between diabetes and prostate cancer incidence. We investigated whether lower prostate cancer incidence among men with diabetes is attributable to lower detection due to prostate cancer screening patterns. METHODS: We studied a population-based historical cohort of 1,034,074 Israeli men aged 21-90 years, without a previous history of cancer. The cohort was followed-up from 2002 to 2012, according to diabetes morbidity, for frequency of prostate-specific antigen (PSA) testing, mean PSA values and detection of prostate cancer, after adjustment for age, ethnic origin, socioeconomic status and PSA testing. RESULTS: In January 2002, 74,756 men had prevalent diabetes. During the 11 year follow-up, 765,483 (74%) remained diabetes-free and 193,835 developed diabetes. Approximately 10% more PSA screening was performed in men with than without diabetes, but the rate of PSA positivity (>4 MUg/l) was 20% lower in men with diabetes. PSA values were already significantly lower in men who developed diabetes than in those who did not, 3 years before diabetes diagnosis. Reduced prostate cancer risk was observed among men with incident diabetes only for low-moderate grade tumours (Gleason score 2 6: adjusted HR 0.83; 95% CI 0.77, 0.89). No association was observed for high grade tumours (Gleason score 7-10: HR 0.99; 95% CI 0.88, 1.11). CONCLUSIONS/INTERPRETATION: Our findings suggest that diabetes comorbidity is a factor to be considered in prostate cancer screening strategies, and specifically in the interpretation of PSA levels. Furthermore, our demonstration of reduced incidence of low-moderate grade but not high-grade prostate cancer tumours among men with diabetes supports the possibility that low PSA levels, rather than lower tumour risk, explains the observed reduced incidence of prostate cancer in men with diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02072902. PMID- 27189069 TI - Late mortality after sepsis. PMID- 27189068 TI - Fluoride exposure in public drinking water and childhood and adolescent osteosarcoma in Texas. AB - PURPOSE: The purpose of this study was to examine the association between fluoride levels in public drinking water and childhood and adolescent osteosarcoma in Texas; to date, studies examining this relationship have been equivocal. Using areas with high and low naturally occurring fluoride, as well as areas with optimal fluoridation, we examined a wide range of fluoride levels in public drinking water. METHODS: This was a population-based case-control study, with both cases and controls obtained from the Texas Cancer Registry. Eligible cases were Texas children and adolescents <20 years old diagnosed with osteosarcoma between 1996 and 2006. Controls were sampled from children and adolescents diagnosed with either central nervous system (CNS) tumors or leukemia during the same time frame. Using geocoded patient addresses at the time of diagnosis, we estimated patients' drinking water fluoride exposure levels based on the fluoride levels of their residence's public water system (PWS). Unconditional logistic regression models were used to assess the association between osteosarcoma and public drinking water fluoride level, adjusting for several demographic risk factors. RESULTS: Three hundred and eight osteosarcoma cases, 598 leukemia controls, and 604 CNS tumor controls met selection criteria and were assigned a corresponding PWS fluoride level. PWS fluoride level was not associated with osteosarcoma, either in a univariable analysis or after adjusting for age, sex, race, and poverty index. Stratified analyses by sex were conducted; no association between PWS fluoride level and osteosarcoma was observed among either males or females. CONCLUSIONS: No relationship was found between fluoride levels in public drinking water and childhood/adolescent osteosarcoma in Texas. PMID- 27189070 TI - Testicular Stem Cells Express Follicle-Stimulating Hormone Receptors and Are Directly Modulated by FSH. AB - Testicular spermatogonial stem cells (SSCs) are a heterogeneous population of stem cells, and definitive marker for the most primitive subset that undergoes asymmetric cell division remains to be identified. A novel subpopulation of pluripotent, very small embryonic-like stem cells (VSELs) has been reported in both human and mouse testes. Follicle-stimulating hormone (FSH) receptors (FSHRs) are expressed on Sertoli cells in testis and on granulosa cells in ovary, but recently FSHRs are reported on VSELs in ovaries, bone marrow, and cord blood. The present study was aimed to investigate whether FSHRs are also expressed on testicular stem cells (VSELs and SSCs) and their possible modulation by FSH using intact and chemoablated (25 mg/kg busulfan) mice. Chemoablated testis was a better model to study stem cell biology since quiescent stem cells survive along with the Sertoli cells in the tubules. Proliferating cell nuclear antigen positive, small-sized cells presumed to be VSELs were clearly visualized, and flow cytometry analysis revealed an increase in LIN-/CD45-/SCA-1+ VSELs from 0.045+/-0.008% to 0.1+/-0.03% of total cells in chemoablated testis after FSH treatment. Very small embryonic-like stem cells expressing nuclear octamer binding transcription factor 4 (OCT-4) and SSCs with cytoplasmic OCT-4 were detected. Very small embryonic-like stem cells (Oct-4A, Sca-1, Nanog), SSCs (Oct 4), and proliferation (Pcna) specific transcripts were upregulated on FSH treatment. Stem cells expressed FSHR and were stimulated by FSH, and Fshr3 was the predominant transcript maximally modulated by FSH. Nuclear OCT-4 and SCA-1 (stem cell antigen 1) positive VSELs are the most primitive stem cells in testis, and FSH stimulates them to undergo asymmetric cell division including self renewal and give rise to SSCs, which in turn proliferate rapidly and undergo clonal expansion and further differentiation. PMID- 27189071 TI - Cathodal Transcranial Direct Current Stimulation (tDCS) to the Right Cerebellar Hemisphere Affects Motor Adaptation During Gait. AB - The cerebellum appears to play a key role in the development of internal rules that allow fast, predictive adjustments to novel stimuli. This is crucial for adaptive motor processes, such as those involved in walking, where cerebellar dysfunction has been found to increase variability in gait parameters. Motor adaptation is a process that results in a progressive reduction in errors as movements are adjusted to meet demands, and within the cerebellum, this seems to be localised primarily within the right hemisphere. To examine the role of the right cerebellar hemisphere in adaptive gait, cathodal transcranial direct current stimulation (tDCS) was administered to the right cerebellar hemisphere of 14 healthy adults in a randomised, double-blind, crossover study. Adaptation to a series of distinct spatial and temporal templates was assessed across tDCS condition via a pressure-sensitive gait mat (ProtoKinetics Zeno walkway), on which participants walked with an induced 'limp' at a non-preferred pace. Variability was assessed across key spatial-temporal gait parameters. It was hypothesised that cathodal tDCS to the right cerebellar hemisphere would disrupt adaptation to the templates, reflected in a failure to reduce variability following stimulation. In partial support, adaptation was disrupted following tDCS on one of the four spatial-temporal templates used. However, there was no evidence for general effects on either the spatial or temporal domain. This suggests, under specific conditions, a coupling of spatial and temporal processing in the right cerebellar hemisphere and highlights the potential importance of task complexity in cerebellar function. PMID- 27189073 TI - Effectiveness and Mechanism of Preoperative Lugol Solution for Reducing Thyroid Blood Flow in Patients with Euthyroid Graves' Disease: Reply. PMID- 27189072 TI - Quantitative and qualitative characterization of Two PD-L1 clones: SP263 and E1L3N. AB - BACKGROUND: Programmed Death Ligand 1 (PD-L1) is an immune modulating protein expressed on the surface of various inflammatory cells, including T Cells, B Cells, dendritic cells, and macrophages. PD-L1 represents an important diagnostic target; expression of PD-L1 on the surface of tumor cells, or within tumor associated immune cells, is an important predictor of likely response to targeted therapies. In this study, we describe the optimization of immunohistochemistry (IHC) assays using two PD-L1 antibodies (SP263 and E1L3N) and compare the performance of the optimized assays. METHODS: Fully automated immunohistochemical assays were optimized for the VENTANA PD-L1 (SP263) Rabbit Monoclonal Antibody and the PD-L1 (E1L3N(r)) XP(r) Rabbit mAb using instruments and detection chemistries from Ventana Medical Systems, Inc. ("SP263 assay" and "E1L3N assay," respectively). Tissue microarrays (TMAs) containing formalin fixed paraffin embedded (FFPE) non-small cell lung cancer (NSCLC) cases were used for the optimization and comparison staining. H scores were used for membrane scoring whereas percent positivity was used for tumor-associated immune cell scoring. RESULTS: One-hundred NSCLC TMA case cores each stained with the SP263 and E1L3N assays were evaluated by two pathologists in a blinded study. Analysis of these specimens showed that the SP263 assay was more sensitive and had a wider dynamic range than the E1L3N assay. For sensitivity, many cases were found to be negative for membrane staining with the E1L3N assay, but had measurable staining with the SP263 assay. Dynamic range was demonstrated by the SP263 assay having well distributed H scores while the E1L3N assay had a significantly higher proportion of cases clustered in the lowest H score bins. For tumor-associated immune cell staining, the two assays identified similar amounts of cells staining in each case, but the SP263 assay gave overall darker staining. CONCLUSION: Since PD-L1 status is important for targeted therapies, having a specific and accurate diagnostic test is crucial for identifying patients who could benefit from these treatments. Due to its staining intensity, scoring range, and pathologist preference, the SP263 IHC assay has been deemed superior to the E1L3N IHC assay. Future clinical utility remains to be determined. PMID- 27189074 TI - Vats Versus Axillary Minithoracotomy in the Management of the Second Episode of Spontaneous Pneumothorax: Cost-Benefit Analysis. AB - BACKGROUND: Video-assisted thoracic surgery (VATS) was considered the gold standard approach in recurrent spontaneous pneumothorax, with unanimous consensus of opinions. The cost-effectiveness analysis in the surgical treatment of recurrence of primary spontaneous pneumothorax (PSP) was carried out comparing VATS with muscle-sparing axillary minithoracotomy (MSAM). METHODS: Between July 2006 and October 2012 we treated 56 patients with a second episode of PSP by VATS or open approach. Time of intervention, prolonged air leaks, duration of pleural drainage, length of hospitalization, and long-term morbidity were evaluated, establishing the relationship between costs and quality-adjusted life for each technique. RESULTS: The assessment of pain and threshold of tenderness was more favorable in VATS in respect to MSAM during the 5 years of follow-up (p = 0.004 and <0.001 at 1st year; p = 0.006 and <0.002 at 5th year). The minimally invasive method was less expensive than axillary minithoracotomy (2443.44 ? vs. 3170.80 ?). The quality-adjusted life expectancy of VATS was better than that of MSAM (57.00 vs. 49.2 at 60 months) as well as the quality-adjusted life year (0.03 at 1st year and 0.13 at 5th year). Incremental cost per life year gained of VATS versus MSAM was between 24,245.33 ? (1st year) and 5776.31 ? (5th year), making it advantageous at 3rd, 4th, and 5th years. CONCLUSIONS: VATS compared to MSAM in the treatment of a second episode of PSP ensured undoubted clinical advantages associated with significant cost savings. PMID- 27189075 TI - Totally Implantable Venous Access Devices: Efforts Are Needed to Standardize Procedures to Avoid Complication: Reply. PMID- 27189076 TI - Postmenopausal Breast Cancer, Aromatase Inhibitors, and Bone Health: What the Surgeon Should Know. AB - Breast cancer, as the most common malignancy in women, remains a major public health issue despite countless advances across decades. Endocrine therapy is the cornerstone of treatment of the hormone-sensitive subtype of breast cancer. The use of aromatase inhibitors (AIs) in the postmenopausal women has extended the survival beyond that of Tamoxifen, but harbors a subset of side effects, most notably accelerated bone loss. This, however, does not occur in all women undergoing treatment. It is vital to identify susceptible patients early, to limit such events, employ early treatment thereof, or alter drug therapy. International trials on AIs, predominantly performed in North American and European females, provide little information on what to expect in women in developing countries. Here, surgeons often prescribe and manage endocrine therapy. The prescribing surgeon should be aware of the adverse effect of the endocrine therapy and be able to attend to side effects. This review highlights clinical and biochemical factors associated with decrease in bone mineral density in an, as yet, unidentified subgroup of postmenopausal women. In the era of personalized medical care, appropriate management of bone health by surgeons based on these factors becomes increasingly important. PMID- 27189077 TI - The TegoTM needleless connector for hemodialysis catheters may protect against catheter colonization. AB - Catheter connectors used in hemodialysis patients are those with open caps to manage high blood flows. However, current guidelines for the prevention of catheter infections recommend closed connectors. TegoTM is a closed connector designed to enable high blood flows. We used an in vitro model to compare the efficacy of TegoTM against contamination with that of standard caps in a real life practice scenario. The model consisted of 200 blood culture bottles (BCB) with an inserted cannula closed either with TegoTM (100) or with open caps (100). BCB were manipulated using two different methods: under aseptic conditions and with gloves contaminated with a 0.05 McFarland Staphylococcus aureus solution. The BCB were incubated at 37 degrees C under continuous shaking for up to 7 days or until positive. When a BCB turned positive, 100 MUL of the fluid was cultured. The positivity rate and time to positivity of the BCB in each method were compared. Overall, 4.0 % of BCB with TegoTM and 52.0 % of BCB with open caps were positive in the sterile model (p < 0.001), whereas all BCB in the contamination model were positive. We did not find differences regarding the median time (hours) to positivity between TegoTM and the standard cap in the contamination model (19.04 vs. 17.87, p = 0.465). In our model, TegoTM proved to be better than the standard cap for the prevention of contamination when the device was handled under optimal conditions. Moreover, it was as efficient as the standard catheter cap in the contamination model. PMID- 27189079 TI - Surface modification of battery electrodes via electroless deposition with improved performance for Na-ion batteries. AB - Sodium-ion batteries (SIBs) are emerging as potential stationary energy storage devices due to the abundance and low cost of sodium. A simple and energy efficient strategy to develop electrodes for SIBs with a high charge/discharge rate is highly desirable. Here we demonstrate that by surface modification of Ge, using electroless deposition in SbCl3/ionic liquids, the stability and performance of the anode can be improved. This is due to the formation of GexSb1 x at the surface leading to better diffusion of Na, and the formation of a stable twin organic and inorganic SEI which protects the electrode. By judicious control of the surface modification, an improvement in the capacity to between 50% and 300% has been achieved at high current densities (0.83-8.4 A g(-1)) in an ionic liquid electrolyte NaFSI-[Py1,4]FSI. The results clearly demonstrate that an electroless deposition based surface modification strategy in ionic liquids offers exciting opportunities in developing superior energy storage devices. PMID- 27189078 TI - Etiology and antibiotic susceptibility of bacterial pathogens responsible for community-acquired urinary tract infections in Poland. AB - Urinary tract infections (UTIs) are some of the most common infections in both community and hospital settings infections. With their high rate of incidence, recurrence, complications, diverse etiologic agents, as well as growing antibiotic resistance, UTIs have proven to be a serious challenge for medical professionals. The aim of this study was to obtain data on the susceptibility patterns of pathogens responsible for UTIs in Poland to currently used antibiotics. A total of 396 bacterial isolates were collected between March and May 2013 from 41 centers in all regions of Poland. The majority of isolates were from adult patients (96.2 %); 144 (37.8 %) patients were diagnosed with uncomplicated UTI, while the remaining 237 (62.2 %) had a complicated infection. The most prevalent pathogen was Escherichia coli (71.4 %), followed by Klebsiella spp. (10.8 %) and the Proteae group (7.6 %). Escherichia coli was responsible for 80.6 % of cases of uncomplicated and 65.8 % of complicated infections. Only 65.8 % of E. coli isolates were susceptible to ciprofloxacin (uncomplicated 75.9 %, complicated 58.3 %), 64.0 % to nitrofurantoin (67.2 %, 62.8 %), 65.1 % to trimethoprim/sulfamethoxazole (68.1 %, 62.8 %), and 66.4 % to fosfomycin (77.6 %, 62.2 %). Among E. coli isolates from all UTIs, only 43.4 % were susceptible to ampicillin, with 47.4 % from uncomplicated compared with 40.4 % from complicated infections; 88.2 % to amoxicillin/clavulanic acid (91.4 % vs. 85.9 % complicated); 90.1 % to cefuroxime (93.1 %, 87.8 %); and 94.1 % to cefotaxime (98.2 %, 91.0 %). Thirty-five strains (10.4 %) were capable of producing extended spectrum beta-lactamases (ESBLs). This study demonstrates an increase in multidrug-resistant strains, especially among the leading pathogens associated with UTIs, including E. coli, Klebsiella spp., and Proteus spp. PMID- 27189080 TI - OPA1 processing in cell death and disease - the long and short of it. AB - The regulation of mitochondrial dynamics by the GTPase OPA1, which is located at the inner mitochondrial membrane, is crucial for adapting mitochondrial function and preserving cellular health. OPA1 governs the delicate balance between fusion and fission in the dynamic mitochondrial network. A disturbance of this balance, often observed under stress and pathologic conditions, causes mitochondrial fragmentation and can ultimately result in cell death. As discussed in this Commentary, these morphological changes are regulated by proteolytic processing of OPA1 by the inner-membrane peptidases YME1L (also known as YME1L1) and OMA1. Long, membrane-bound forms of OPA1 are required for mitochondrial fusion, but their processing to short, soluble forms limits fusion and can facilitate mitochondrial fission. Excessive OPA1 processing by the stress-activated protease OMA1 promotes mitochondrial fragmentation and, if persistent, triggers cell death and tissue degeneration in vivo The prevention of OMA1-mediated OPA1 processing and mitochondrial fragmentation might thus offer exciting therapeutic potential for human diseases associated with mitochondrial dysfunction. PMID- 27189081 TI - Nitric oxide mediates stretch-induced Ca2+ oscillation in smooth muscle. AB - The stretching of smooth muscle tissue modulates contraction through augmentation of Ca(2+) transients, but the mechanism underlying stretch-induced Ca(2+) transients is still unknown. We found that mechanical stretching and maintenance of mouse urinary bladder smooth muscle strips and single myocytes at 30% and 18% beyond the initial length, respectively, resulted in Ca(2+) oscillations. Experiments indicated that mechanical stretching remarkably increased the production of nitric oxide (NO) as well as the amplitude and duration of muscle contraction. Stretch-induced Ca(2+) oscillations and contractility increases were completely abolished by the NO inhibitor L-NAME or eNOS (also known as NOS3) gene inactivation. Moreover, exposure of eNOS-knockout myocytes to exogenous NO donor induced Ca(2+) oscillations. The stretch-induced Ca(2+) oscillations were greatly inhibited by the selective inositol 1,4,5-trisphosphate receptor (IP3R) inhibitor xestospongin C and partially inhibited by ryanodine. Moreover, the stretch induced Ca(2+) oscillations were also suppressed by the phosphoinositide 3-kinase (PI3K) inhibitor LY294002, but not by the soluble guanylyl cyclase (sGC) inhibitor ODQ. These results suggest that stretching myocyte and maintenance at a certain length results in Ca(2+) oscillations that are NO dependent , and sGC and cGMP independent, and results from the activation of PI3K in smooth muscle. PMID- 27189082 TI - Whole genome nucleosome sequencing identifies novel types of forensic markers in degraded DNA samples. AB - In the case of mass disasters, missing persons and forensic caseworks, highly degraded biological samples are often encountered. It can be a challenge to analyze and interpret the DNA profiles from these samples. Here we provide a new strategy to solve the problem by taking advantage of the intrinsic structural properties of DNA. We have assessed the in vivo positions of more than 35 million putative nucleosome cores in human leukocytes using high-throughput whole genome sequencing, and identified 2,462 single nucleotide variations (SNVs), 128 insertion-deletion polymorphisms (indels). After comparing the sequence reads with 44 STR loci commonly used in forensics, five STRs (TH01, TPOX, D18S51, DYS391, and D10S1248)were matched. We compared these "nucleosome protected STRs" (NPSTRs) with five other non-NPSTRs using mini-STR primer design, real-time PCR, and capillary gel electrophoresis on artificially degraded DNA. Moreover, genotyping performance of the five NPSTRs and five non-NPSTRs was also tested with real casework samples. All results show that loci located in nucleosomes are more likely to be successfully genotyped in degraded samples. In conclusion, after further strict validation, these markers could be incorporated into future forensic and paleontology identification kits, resulting in higher discriminatory power for certain degraded sample types. PMID- 27189083 TI - Mossbauer Spectroscopy of Iron Carbides: From Prediction to Experimental Confirmation. AB - The Mossbauer spectroscopy of iron carbides (alpha-Fe, gamma'-FeC, eta-Fe2C, zeta Fe2C, chi-Fe5C2, h-Fe7C3, theta-Fe3C, o-Fe7C3, gamma'-Fe4C, gamma''-Fe4C, and alpha'-Fe16C2) is predicted utilizing the all electron full-potential linearized augmented plane wave (FLAPW) approach across various functionals from LDA to GGA (PBE, PBEsol, and GGA + U) to meta-GGA to hybrid functionals. To validate the predicted MES from different functionals, the single-phase chi-Fe5C2 and theta Fe3C are synthesized in experiment and their experimental MES under different temperature (from 13 K to 298 K) are determined. The result indicates that the GGA functional (especially, the PBEsol) shows remarkable success on the prediction of Mossbauer spectroscopy of alpha-Fe, chi-Fe5C2 and theta-Fe3C with delocalized d electrons. From the reliable simulations, we propose a linear relationship between Bhf and MUB with a slope of 12.81 T/MUB for iron carbide systems and that the proportionality constant may vary from structure to structure. PMID- 27189084 TI - Can we improve transthoracic echocardiography training in non-cardiologist residents? Experience of two training programs in the intensive care unit. AB - BACKGROUND: To evaluate the diagnostic performances of two training programs for residents with no prior ultrasound experience to reach competences in extended basic critical care transthoracic echocardiography (CCE) including Doppler capabilities. METHODS: This is a prospective observational study in two intensive care units of teaching hospitals. Group I (five residents) completed a short training program (4-h theory; 3-h practical); group II (six residents) completed a longer training program (6-h theory; 12-h practical). The residents and an expert examined all patients who required a transthoracic echocardiography. Their agreement studied by Cohen's kappa coefficient, concordance coefficient correlation (CCC) and Bland-Altman plots was used as an indicator of program effectiveness. RESULTS: Group I performed 136 CCEs (mean/resident 27; range 22 32; 65 in ventilated patients) in 115 patients (62 men; 64 +/- 18 years; Simplified Acute Physiologic Score [SAPS] II 37 +/- 18). Group II performed 158 CCEs (mean/resident 26; range 21-31; 65 in ventilated patients) in 108 patients (64 men; 58 +/- 17 years; SAPS II 42 +/- 22). Both groups adequately assessed left ventricular (LV) systolic function (kappa 0.75, 95 % confidence interval [CI] 0.64-0.86; kappa 0.77, 95 % CI 0.66-0.88, respectively) and pericardial effusion (kappa 0.83, 95 % CI 0.67-0.99; kappa 0.76, 95 % CI 0.60-0.93, respectively). Group II appraised severe right ventricular dilatation and significant left-sided valve disease with good to very good agreement (kappa 0.80, 95 % CI 0.56-0.96; kappa 0.79, 95 % CI 0.66-0.93, respectively). Regarding left ventricular ejection fraction, E/A ratio, E/e' ratio and aortic peak velocity assessed by group II, CCCs were all >0.70 and the bias (mean difference) +/-SD on Bland-Altman analysis was 1.3 +/- 8.8 %, 0 +/- 0.3, 0.4 +/- 2.2 and 0.1 +/- 0.4 m/s, respectively. Detection of paradoxical septum (kappa 0.65, 95 % CI 0.37-0.93), of heterogeneous LV contraction (kappa 0.49, 95 % CI 0.33-0.65) and of respiratory variation of the inferior vena cava (kappa 0.27, 95 % CI 0.09 0.45), as well as stroke volume measurement (CCC 0.65, 95 % CI 0.54-0.74; bias +/ SD -1.4 +/- 4.7 cm), was appraised by group II with moderate agreement requiring probably more comprehensive training. CONCLUSIONS: Although a training program blending 6-h theory and 12-h practical may be adapted to achieve some essential competences, it seems to be insufficiently to perform a complete extended basic critical care transthoracic echocardiography including Doppler capabilities. PMID- 27189085 TI - A case of hysteroscopic resection of cervical pregnancy after successful treatment with systematic methotrexate. PMID- 27189086 TI - A Randomized Trial of Daily Prednisone versus Pulsed Dexamethasone in Treatment Naive Adult Patients with Immune Thrombocytopenia: EIS 2002 Study. AB - Oral prednisone is considered the standard first-line therapy of adult immune thrombocytopenia, but its long-term efficacy is limited. We performed a prospective, randomized, multicenter trial comparing daily prednisone (1-2 mg/kg/day for 2-4 weeks with subsequent dose reduction) with six 3-week cycles of pulsed dexamethasone (0.6 mg/kg/day, days 1-4). The primary endpoint was remission duration. Of 26 patients enrolled, 22 were evaluable for response. Nine were treated with prednisone and 13 with dexamethasone. The median follow-up was 46 months. The initial response rate (PLT >=50 * 109/l) was 100% in both groups. Long-term remissions were significantly more frequent with pulsed dexamethasone than with daily prednisone (12 months posttreatment: 77 vs. 22%; p = 0.027). The side effects were similar, but patients on dexamethasone suffered significantly more often from insomnia, while patients on prednisone tended to have more infectious complications. Although the cumulative cortisol equivalent dose was comparable during the first 4 weeks of therapy, it was significantly higher in the dexamethasone arm than in the prednisone arm during the ensuing treatment period. We conclude that repeated cycles of pulsed dexamethasone are a good alternative to daily prednisone as a first-line treatment of immune thrombocytopenia. The duration and intensity of glucocorticoid therapy are important determinants of treatment outcome. PMID- 27189087 TI - Tian Jiu therapy for allergic rhinitis: study protocol for a randomized controlled trial. AB - BACKGROUND: Allergic rhinitis (AR) is one of the most common allergic diseases. The conventional treatments of allergic rhinitis are oral anti-histamines, the use of intranasal corticosteroids, and immunotherapy. Dissatisfied with the ineffectiveness and side effects of these treatments, substantial numbers of patients are turning to alternative treatments like Chinese herbal medicine, particularly Tian Jiu (TJ). TJ is a form of moxibustion in which herbal patches are applied to specific acupoints on the skin. This study aims to investigate the efficacy and safety of TJ in the treatment of allergic rhinitis. METHODS/DESIGN: This will be a prospective, randomized, single-blinded, controlled trial in patients with AR. After a 1-week run-in period, eligible subjects will be randomly assigned to the TJ group, placebo-control group or waitlist-control group. The TJ and placebo-control groups will undergo a 4-week treatment with one session per week and one 4-week post-treatment follow-up. Participants in the waitlist-control group will not receive any treatment during the first 4 weeks but will be required to be assessed. The primary outcome will be the change in the weekly average of the Total Nasal Symptom Score recorded from baseline to the end of treatment. The secondary outcomes will be change in symptoms and change in need for medication between baseline and the end of treatment by using the Rhinitis Quality of Life Questionnaire. Rescue medication (RM) needs will be measured using an RM score, comprising the weekly sum of daily assessments and any form of systemic steroids for allergic rhinitis. DISCUSSION: This study will be the first study to compare TJ treatment for allergic rhinitis with a placebo control group, and a waitlist-control group. The investigation of TJ for allergic rhinitis will also suggest recommendations for clinical practice. The results of this study are expected to provide consolidated evidence for the effectiveness and safety of TJ for the treatment of patients with allergic rhinitis. TRIAL REGISTRATION: NCT02470845 (17 May 2015). PMID- 27189090 TI - [Chlamydia trachomatis infection in mother and child; the importance of a complete history and efficient interdisciplinary communication]. AB - General practitioners and paediatricians are frequently confronted with coughing infants. The age of the infant, the history of both mother and child, as well as the current maternal condition may provide important diagnostic information. A 4 week-old male infant was referred to the paediatrician with a persistent cough. He was admitted to hospital with dyspnoea and need for supplemental oxygen. Meanwhile, his mother was admitted with unexplained abdominal pain and elevated laboratory inflammation markers. Her history revealed an ectopic pregnancy. The infant's condition, for which the initial differential diagnosis was viral bronchiolitis or whooping cough, deteriorated. His medical history revealed a purulent conjunctivitis. Chlamydia trachomatis PCR turned out to be positive in both mother and child. C. trachomatis pneumonia is a common, yet often overlooked cause of cough in infants. This clinical lesson emphasises the importance of a complete history and efficient communication between medical specialists. PMID- 27189091 TI - [Hydrofluoric acid burns]. AB - Hydrofluoric acid is increasingly used as a rust remover and detergent. Dermal contact with hydrofluoric acid results in a chemical burn characterized by severe pain and deep tissue necrosis. It may cause electrolyte imbalances with lethal consequences. It is important to identify high-risk patients. 'High risk' is defined as a total affected body area > 3% or exposure to hydrofluoric acid in a concentration > 50%. We present the cases of three male patients (26, 31, and 39 years old) with hydrofluoric acid burns of varying severity and describe the subsequent treatments. The application of calcium gluconate 2.5% gel to the skin is the cornerstone of the treatment, reducing pain as well as improving wound healing. Nails should be thoroughly inspected and possibly removed if the nail is involved, to ensure proper healing. In high-risk patients, plasma calcium levels should be evaluated and cardiac monitoring is indicated. PMID- 27189089 TI - Paracoccidioides brasiliensis infection promotes thymic disarrangement and premature egress of mature lymphocytes expressing prohibitive TCRs. AB - BACKGROUND: Paracoccidioidomycosis, a chronic granulomatous fungal disease caused by Paracoccidioides brasiliensis yeast cells affects mainly rural workers, albeit recently cases in immunosuppressed individuals has been reported. Protective immune response against P. brasiliensis is dependent on the activity of helper T cells especially IFN-gamma-producing Th1 cells. It has been proposed that Paracoccidioides brasiliensis is able to modulate the immune response towards a permissive state and that the thymus plays a major role in it. METHODS: In this paper, we show that acute infection of BALB/c mice with P. brasiliensis virulent isolate (Pb18) might cause alterations in the thymic environment as well as the prohibitive TCR-expressing T cells in the spleens. RESULTS: After seven days of infection, we found yeast cells on the thymic stroma, the thymic epithelial cells (TEC) were altered regarding their spatial-orientation and inflammatory mediators gene expression was increased. Likewise, thymocytes (differentiating T cells) presented higher migratory ability in ex vivo experiments. Notwithstanding, P. brasiliensis-infected mice showed an increased frequency of prohibitive TCR expressing T cells in the spleens, suggesting that the selection processes that occur in the thymus may be compromised during the acute infection. CONCLUSION: In this paper, for the first time, we show that acute infection with Paracoccidioides brasiliensis yeast cells promotes thymic alterations leading to a defective repertoire of peripheral T cells. The data presented here may represent new mechanisms by which P. brasiliensis subverts the immune response towards the chronic infection observed in humans. PMID- 27189092 TI - [Recanalisation after occlusion of the internal carotid artery]. AB - BACKGROUND: In patients who have suffered a transient ischemic attack (TIA) or ischaemic stroke, diagnostic imaging often reveals an occlusion in the extracranial internal carotid artery (ICA) on the symptomatic side. It is generally assumed that no follow-up is needed. CASE DESCRIPTION: A 57-year-old man reported to the emergency department with global aphasia. Two weeks previously he had been diagnosed with an occlusion of the left ICA following a TIA. On the basis of CT angiography we diagnosed an ischaemic stroke in the left middle cerebral artery territory and a severe stenosis of the left ICA. Several days later the patient underwent a successful carotid endarterectomy. CONCLUSION: Following an acute symptomatic occlusion of the extracranial ICA, recanalisation of the artery can take place. In these patients we advise considering a repeat of the diagnostic imaging of the ICA within a week. PMID- 27189088 TI - HIF-1alpha-PDK1 axis-induced active glycolysis plays an essential role in macrophage migratory capacity. AB - In severely hypoxic condition, HIF-1alpha-mediated induction of Pdk1 was found to regulate glucose oxidation by preventing the entry of pyruvate into the tricarboxylic cycle. Monocyte-derived macrophages, however, encounter a gradual decrease in oxygen availability during its migration process in inflammatory areas. Here we show that HIF-1alpha-PDK1-mediated metabolic changes occur in mild hypoxia, where mitochondrial cytochrome c oxidase activity is unimpaired, suggesting a mode of glycolytic reprogramming. In primary macrophages, PKM2, a glycolytic enzyme responsible for glycolytic ATP synthesis localizes in filopodia and lammelipodia, where ATP is rapidly consumed during actin remodelling processes. Remarkably, inhibition of glycolytic reprogramming with dichloroacetate significantly impairs macrophage migration in vitro and in vivo. Furthermore, inhibition of the macrophage HIF-1alpha-PDK1 axis suppresses systemic inflammation, suggesting a potential therapeutic approach for regulating inflammatory processes. Our findings thus demonstrate that adaptive responses in glucose metabolism contribute to macrophage migratory activity. PMID- 27189093 TI - [Coronary artery calcium score in clinical practice]. AB - Since the beginning of the 1990s it is possible to obtain images of the heart using CT technology to visualise coronary calcifications. The amount of coronary calcification can be quantified with a coronary artery calcium score. Today, there is sufficient scientific evidence that justifies the use of the coronary artery calcium score in selected patients. In asymptomatic patients, the coronary artery calcium score can be used for more precise and tailored risk stratification for the occurrence of future cardiovascular events. The absence of coronary calcification is associated with a good prognosis. In addition, the coronary artery calcium score can also be used as the initial test in symptomatic patients, to dictate treatment strategies going forward. PMID- 27189094 TI - [Effective communication with talkative patients: 10 tips]. AB - Consultations with talkative patients present a challenge to doctors. It is difficult to gather all the necessary information within the available time, without damaging the doctor-patient relationship. Based on the listed existing literature and doctors' experiences, we present ten tips for gathering information from talkative patients in an effective manner whilst maintaining a good therapeutic alliance. In consultations with talkative patients, it is important to explore the cause of patients' talkativeness and to adapt one's communication approach accordingly.- Familiar communication strategies such as 'summarizing' can still be applied. When taking this route, a more directive communication approach--e.g. by means of a 'closed-ended summary'--can prevent the patient interrupting the doctor or departing from his subject. There are strategies aimed at avoiding a damaging effect to the doctor-patient relationship when applying this approach: don't be overly directive, make the patient co responsible for efficient time management in the consultation, and make use of empathic interrupting and humour. PMID- 27189095 TI - [The Amsterdam wrist rules: the multicenter prospective derivation and external validation of a clinical decision rule for the use of radiography in acute wrist trauma]. AB - BACKGROUND: Although only 39% of patients with wrist trauma have sustained a fracture, the majority of patients is routinely referred for radiography. The purpose of this study was to derive and externally validate a clinical decision rule that selects patients with acute wrist trauma in the Emergency Department (ED) for radiography. METHOD: This multicenter prospective study consisted of three components: (1) derivation of a clinical prediction model for detecting wrist fractures in patients following wrist trauma; (2) external validation of this model; and (3) design of a clinical decision rule. The study was conducted in the EDs of five Dutch hospitals: one academic hospital (derivation cohort) and four regional hospitals (external validation cohort). We included all adult patients with acute wrist trauma. The main outcome was fracture of the wrist (distal radius, distal ulna or carpal bones) diagnosed on conventional X-rays. RESULTS: A total of 882 patients were analyzed; 487 in the derivation cohort and 395 in the validation cohort. We derived a clinical prediction model with eight variables: age; sex, swelling of the wrist; swelling of the anatomical snuffbox, visible deformation; distal radius tender to palpation; pain on radial deviation and painful axial compression of the thumb. The Area Under the Curve at external validation of this model was 0.81 (95% CI: 0.77-0.85). The sensitivity and specificity of the Amsterdam Wrist Rules (AWR) in the external validation cohort were 98% (95% CI: 95-99%) and 21% (95% CI: 15%-28). The negative predictive value was 90% (95% CI: 81-99%). CONCLUSION: The Amsterdam Wrist Rules is a clinical prediction rule with a high sensitivity and negative predictive value for fractures of the wrist. Although external validation showed low specificity and 100 % sensitivity could not be achieved, the Amsterdam Wrist Rules can provide physicians in the Emergency Department with a useful screening tool to select patients with acute wrist trauma for radiography. The upcoming implementation study will further reveal the impact of the Amsterdam Wrist Rules on the anticipated reduction of X-rays requested, missed fractures, Emergency Department waiting times and health care costs. PMID- 27189096 TI - [Patient preferences versus evidence-based medicine: did the pioneers of evidence based medicine take the patient's preferences into account?]. AB - A patient's values and preferences are one of the three 'pillars' of evidence based medicine (EBM). How can we explain that this one pillar has hardly been elaborated in the EBM-literature?? Were the EBM pioneers really committed to the patient's preferences, were they not ready yet, or were they not committed at all? In key international EBM publications dated between 1985 and 2000, we only found sympathetic, yet vague, statements lacking concrete content. In the Netherlands, a Health Council report set the tone with a sense of fear for 'consumer medicine'. In addition to an overly optimistic view of the past, in 2014 Greenhalgh sketched a vision of the future of EBM in which the sympathetic comments about patient preferences are finally made concrete. The EBM movement has already successfully adapted to social developments in the past; therefore, there is reason for optimism. PMID- 27189097 TI - [Safety and efficacy of ketamine for pain relief]. AB - Intravenous ketamine treatment is frequently used for the management of chronic pain, especially in those patients who do not benefit from other therapies. In this commentary we discuss the efficacy of ketamine for relief of chronic pain and ketamine's safety profile. A review of the literature indicates that only a few studies show that intravenous ketamine has analgesic effects that persist beyond the infusion period, an effect that occurs in about two-thirds of patients. Ketamine has multiple safety issues, ranging from psychotomimetic and schizotypal symptoms, sympathetic stimulation, tachycardia and hypertension, and damage to the liver and the urogenital tract. Damage to the urogenital tract seems to be restricted to individuals who chronically abuse ketamine. We indicate the need for large randomized trials in which ketamine is compared with an 'active' placebo. PMID- 27189098 TI - [General practitioners as gatekeepers: Better health care than in countries with self-referral to specialists?]. AB - In the Netherlands and a number of other European countries general practitioners are the gatekeepers for specialist and hospital care. European health care systems with gatekeeping general practitioners, i.e. those with comprehensive, strong primary care, perform better on a number of health indicators and on equity. However, it is less clear if gatekeeping health care systems have lower health expenditure. There is ongoing debate on whether gatekeeping plays a role in diagnostic delay of cancers. At health care system level research is being hampered by small numbers and should be combined with in-depth research into health care mechanisms. PMID- 27189100 TI - Quantification of nitrergic neurons in the myenteric plexus of gastric antrum and ileum of healthy and diabetic dogs. AB - Diabetes mellitus (DM) determines a wide array of severe clinical complications including gastrointestinal motility disorders. The present study investigates the effects of spontaneous DM on the intramural innervation and in particular on nitrergic neurons of the myenteric plexus (MP) of the canine gastric antrum and ileum. Specimens of antrum and ileum from eight control-dogs and five insulin dependent DM-dogs were collected. MP neurons were immunohistochemically identified with the anti-HuC/HuD antibody, while nitrergic neurons were identified with the antibody anti-neuronal nitric oxide synthase (nNOS). The density of HuC/HuD-immunoreactive (IR) neurons was determined and the nitrergic neurons were quantified as a relative percentage, in consideration of the total number of HuC/HuD-IR neurons. Furthermore, the density of nitrergic fibers in the muscular layers was calculated. Data were expressed as mean+/-standard deviation. Compared to control-dogs, no significant differences resulted in the density of HuC/HuD-IR neurons in the antrum and ileum of DM-dogs; however, HuC/HuD immunolabeling showed nuclear localization and fragmentation in DM-dogs. In the stomachs of control- and DM-dogs, the percentages of nitrergic neurons were 30+/ 6% and 25+/-2%, respectively (P=0.112). In the ileum of the control-dogs, the percentage of nitrergic neurons was 29+/-5%, while in the DM-dogs, it was significantly reduced 19+/-5% (P=0.006). The density of nNOS-IR nervous fibers was meaningful reduced in either the tracts considered. Notably, the ganglia of DM-dogs showed also a thickening of the periganglionic connective tissue. These findings indicate that DM in dogs induce modification of the myenteric neurons and, in particular, of the nitrergic neuronal subpopulation. PMID- 27189099 TI - Aligned Nanotopography Promotes a Migratory State in Glioblastoma Multiforme Tumor Cells. AB - Glioblastoma multiforme (GBM) is an aggressive, Grade IV astrocytoma with a poor survival rate, primarily due to the GBM tumor cells migrating away from the primary tumor site along the nanotopography of white matter tracts and blood vessels. It is unclear whether this nanotopography influences the biomechanical properties (i.e. cytoskeletal stiffness) of GBM tumor cells. Although GBM tumor cells have an innate propensity to migrate, we believe this capability is enhanced due to the influence of nanotopography on the tumor cells' biomechanical properties. In this study, we used an aligned nanofiber film that mimics the nanotopography in the tumor microenvironment to investigate the mechanical properties of GBM tumor cells in vitro. The data demonstrate that the cytoskeletal stiffness, cell traction stress, and focal adhesion area were significantly lower in the GBM tumor cells compared to healthy astrocytes. Moreover, the cytoskeletal stiffness was significantly reduced when cultured on aligned nanofiber films compared to smooth and randomly aligned nanofiber films. Gene expression analysis showed that tumor cells cultured on the aligned nanotopography upregulated key migratory genes and downregulated key proliferative genes. Therefore, our data suggest that the migratory potential is elevated when GBM tumor cells are migrating along aligned nanotopographical substrates. PMID- 27189102 TI - [In Process Citation]. PMID- 27189101 TI - Spin-labelled photo-cytotoxic diazido platinum(iv) anticancer complex. AB - We report the synthesis and characterisation of the nitroxide spin-labelled photoactivatable Pt(iv) prodrug trans,trans,trans-[Pt(N3)2(OH)(OCOCH2CH2CONH TEMPO)(Py)2] (Pt-TEMPO, where TEMPO = 2,2,6,6-tetramethylpiperidine 1-oxyl). Irradiation with blue visible light gave rise to Pt(ii) and azidyl as well as nitroxyl radicals. Pt-TEMPO exhibited low toxicity in the dark, but on photoactivation was as active towards human ovarian cancer cells as the clinical photosensitizer chlorpromazine and much more active than the anticancer drug cisplatin under the conditions used. PMID- 27189103 TI - [In Process Citation]. PMID- 27189104 TI - [Blaschkos linjer i akutmodtagelsen]. PMID- 27189105 TI - [Hepatitis after chewing of khat leaves]. AB - Chewing of leaves from the Catha edulis (khat) plant has amphetamine-like, stimulating effects and is used in rituals among East African men. In recent years, a possible liver-toxic effect has been observed in Somali immigrants in Western countries and has in severe cases led to death or liver transplantation. It is discussed whether the liver insufficiency represents a severe ethnic variant of autoimmune hepatitis, or a khat-induced hepatitis with autoimmune features. We describe six patients with Somalian background and possibly khat induced toxic hepatitis. PMID- 27189106 TI - [Basal cell carcinoma surgery]. AB - Basal cell carcinoma (BCC) is the most common type of cancer in humans. The lifetime risk of developing BCC is 30%. The scope of the treatment is total eradication of the tumour followed by preservation of functionality and optimal cosmetic results. The risk of recurrence after treatment is highest in the tumours with aggressive growth patterns, in tumours located in the facial H-zone and in recurrent tumours. The optimal treatment of high-risk BCCs is surgical excision or radiotherapy. Low-risk tumours may be treated with cryotherapy, curettage, photodynamic therapy or topical agents. PMID- 27189108 TI - Ideal free distribution of metabolic activity: Implications of seasonal metabolic activity patterns on competitive coexistence. AB - The seasonal distribution of metabolic activity determines how much individuals experience different aspects of a periodically changing environment. Seasonal metabolic-activity patterns of coexisting species may differ significantly despite their shared environmental conditions, suggesting that interspecific diversification of this trait has a major role in the coexistence of competing species. In the present study the effect of the seasonal distribution of metabolic activity on intra- and interspecific competition is investigated in a consumer-resource model. It is shown that, in a periodically changing environment, for each environmental preference pattern there is an ideal seasonal distribution of metabolic activity, which results in maximum resource utilisation efficiency and competitive superiority. Contrary to the common interpretation of temporal niche segregation, opposing species-specific seasonal preferences are not a sufficient condition for the coexistence of two species on a population dynamical time scale. A necessary and sufficient condition for coexistence is the temporal segregation of the species via different seasonal activity distributions. However, coexistence is evolutionarily stable only if seasonal metabolic activities and preferences are positively correlated. PMID- 27189107 TI - [Analyses of deaths can provide meaningful learning]. AB - Learning based on deceased patients has provided medicine with substantial knowledge and is still a source of new information. The basic learning approach has been autopsies, but focus has shifted towards analysis of registry data. This article evaluates different ways to analyse the natural deaths, including autopsies, audits, clinical databases and hospital standardised mortality ratios in regard of clinical learning. We claim that data-powered analysis cannot stand alone, and recommend that clinicians should organise multidisciplinary theoretically based audits, in order to keep learning from the deceased. PMID- 27189109 TI - Chronic administration of Angelica sinensis polysaccharide effectively improves fatty liver and glucose homeostasis in high-fat diet-fed mice. AB - This study aimed to investigate the therapeutic effects of Angelica sinensis polysaccharide (ASP), an active component derived from a water extract of Angelica sinensis, in high-fat diet (HFD)-fed BALB/c mice. The potential mechanisms underlying the activity of this compound were also considered. Specifically, serum and hepatic biochemical parameters were evaluated, and key proteins involved in the lipid/glucose metabolism were analyzed. Long-term feeding with a HFD induced severe fatty liver and hyperglycemia. Histological examination clearly showed that ASP reduced lipid accumulation in the liver and attenuated hepatic steatosis in HFD-fed mice. In addition, ASP markedly alleviated serum and liver lipid disorders and fatty liver via the upregulation of PPARgamma expression and the activation of adiponectin-SIRT1-AMPK signaling. Furthermore, ASP also significantly relieved severe oxidative stress, demonstrating that ASP might attenuate nonalcoholic fatty liver disease via a "two-hit" mechanism. In addition, ASP reduced blood glucose levels and ameliorated insulin resistance via the regulation of related metabolic enzymes and by activating the PI3K/Akt pathway in HFD-fed mice. Our findings revealed that ASP might be used as an alternative dietary supplement or health care product to ameliorate metabolic syndrome in populations that consistently consume HFDs. PMID- 27189110 TI - Early Lung Computed Tomography Scan after Allogeneic Hematopoietic Stem Cell Transplantation. AB - A lung computed tomography (CT) scan is essential for diagnosing lung diseases in hematopoietic stem cell transplantation (HSCT) recipients. As a result, lung CT scans are increasingly prescribed in the early phase after allogeneic HSCT, with no assessment of the added value for global patient management. Among 250 patients who underwent allogeneic HSCT in our center over a 2-year period, we evaluated 68 patients who had at least 1 lung CT scan within the first 30 days post-transplantation. The median interval between allogeneic HSCT and lung CT scan was 8.5 days. Patients who underwent an early lung CT scan were more immunocompromised and had a more severe course. Fever was the main indication for the CT scan (78%). The lung CT scan was abnormal in 52 patients, including 17 patients who had an abnormal pre-HSCT CT scan. A therapeutic change was noted in 37 patients (54%) within 24 hours after the lung CT scan. The main changes included the introduction of corticosteroids (n = 23; 62%), especially in patients with a normal CT scan (89%). In univariate models, we found that a normal pretransplantation CT scan (P = .002), the absence of either dyspnea (P = .029) or hypoxemia (P = .015), and a serum C-reactive protein level <10 mg/L (P = .004) were associated with a normal post-HSCT lung CT scan. We found that the association of these variables could predict the normality of early post-HSCT lung CT scans. Pretransplantation lung CT scans are useful for the interpretation of subsequent lung CT scans following allogeneic HSCT, which are frequently abnormal. Early post-HSCT lung CT scans are helpful in patient management, but prescriptions could be more targeted. PMID- 27189111 TI - STAT6 Loss in Dedifferentiated Solitary Fibrous Tumor. PMID- 27189112 TI - Bioinspired Polyelectrolyte-Assembled Graphene-Oxide-Coated C18 Composite Solid Phase Microextraction Fibers for In Vivo Monitoring of Acidic Pharmaceuticals in Fish. AB - A novel solid-phase microextraction (SPME) fiber was prepared by gluing poly(diallyldimethylammonium chloride) (PDDA) assembled graphene oxide (GO) coated C18 composite particles (C18@GO@PDDA) onto a quartz fiber with polyaniline (PANI). The fiber surface coating was sequentially modified with bioinspired polynorepinephrine, which provided a smooth biointerface and makes the coating suitable for in vivo sampling. The novel custom-made coating was used to extract acidic pharmaceuticals, and high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) was employed for analysis. The custom-made coating exhibited a much higher extraction efficiency than the previously used commercial polydimethylsiloxane (PDMS) and polyacrylate (PA) coatings. The custom-made coating also possessed satisfactory stability (the relative standard deviations (RSDs) ranged from 1.60% to 10.3% for six sampling-desorption cycles), interfiber reproducibility (the RSDs ranged from 2.61% to 11.5%), and resistance to matrix effects. The custom-made fibers were used to monitor the presence of acid pharmaceuticals in dorsal-epaxial muscle of living fish, and satisfactory sensitivities (limits of detection ranged from 0.13 ng/g to 7.56 ng/g) were achieved. The accuracies were verified by the comparison with liquid extraction. Moreover, the novel fibers were successfully used to monitor the presence of acidic pharmaceuticals in living fish, which demonstrated that the custom-made fibers were feasible for possible long-term in vivo continuous pharmaceutical monitoring. PMID- 27189113 TI - beta-Perfluoroalkyl-substituted pyrrole as an anion-responsive pi-electronic system through a single NH moiety. AB - A pyrrole derivative with two perfluorohexyl (C6F13) chains at the beta-positions was synthesized. The significant electron-withdrawing properties of the beta perfluoroalkyl chains induced fascinating anion-binding behaviour. PMID- 27189115 TI - Photoswitching of Conductance of Diarylethene-Gold Nanoparticle Network Based on the Alteration of pi-Conjugation. AB - Diarylethenes, which have same core structures but have different positions of thiol groups that are bound to gold nanoparticles, were prepared. In one diarylethene, which has two thiol groups at the positions equivalent to 5,5' positions of di(3-thienyl)ethene, the pi-connectivity between two thiol groups increases upon photocyclization, but in the other diarylethene, which has two thiol groups at 2- and 5-positions of one of the 3-thenyl group, the pi connectivity decreases upon photocyclization. The gold nanoparticle networks of these diarylethenes were prepared and the change in conductance was measured upon alternate irradiation with UV and visible light. For two diarylethenes, the direction of the photoswitching was opposite, reflecting the difference in the pi connectivity. The result suggests that the topology of pi-conjugation between electrodes is the decisive factor in the conductance of gold nanoparticle network. PMID- 27189114 TI - Wordbank: an open repository for developmental vocabulary data. AB - The MacArthur-Bates Communicative Development Inventories (CDIs) are a widely used family of parent-report instruments for easy and inexpensive data-gathering about early language acquisition. CDI data have been used to explore a variety of theoretically important topics, but, with few exceptions, researchers have had to rely on data collected in their own lab. In this paper, we remedy this issue by presenting Wordbank, a structured database of CDI data combined with a browsable web interface. Wordbank archives CDI data across languages and labs, providing a resource for researchers interested in early language, as well as a platform for novel analyses. The site allows interactive exploration of patterns of vocabulary growth at the level of both individual children and particular words. We also introduce wordbankr, a software package for connecting to the database directly. Together, these tools extend the abilities of students and researchers to explore quantitative trends in vocabulary development. PMID- 27189116 TI - Influence of Fe loadings on desulfurization performance of activated carbon treated by nitric acid. AB - A series of Fe supported on activated carbon treated by nitric acid are prepared by incipient wetness impregnation with ultrasonic assistance and characterized by N2 adsorption-desorption, X-ray diffraction, Fourier transform infrared spectrum and X-ray photoelectron spectroscopy. It has shown that Fe loadings significantly influence the desulfurization activity. Fe/NAC5 exhibits an excellent removal ability of SO2, corresponding to breakthrough sulfur capacity of 323 mg/g. With the increasing Fe loadings, the generated Fe3O4 and Fe2SiO4 increase, but Fe2(SO4)3 is observed after desulfurization. Fe/NAC1 has a Brunauer-Emmett-Teller (BET) surface area of 925 m2/g with micropore surface area of 843 m2/g and total pore volume of 0.562 cm3/g including a micropore volume of 0.300 cm3/g. With the increasing Fe loadings, BET surface area and micropore volume decrease, and those of Fe/NAC10 decrease to 706 m2/g and 0.249 cm3/g. The Fe loadings influence the pore-size distribution, and SO2 adsorption mainly reacts in micropores at about 0.70 nm. C=O and C-O are observed for all samples before SO2 removal. After desulfurization, the C-O stretching is still detected, but the C=O stretching vibration of carbonyl groups disappears. The stretching of S-O or S=O in sulfate is observed at 592 cm-1 for the used sample, proving that the existence of [Formula: see text]. PMID- 27189117 TI - Structural evaluations and temperature dependent photoluminescence characterizations of Eu(3+)-activated SrZrO3 hollow spheres for luminescence thermometry applications. AB - This research is focused on the temperature sensing ability of perovskite SrZrO3:Eu(3+) hollow spheres synthesized via the sol-gel method followed by heating. The Rietveld refinement indicated that the precursors annealed at 1100 degrees C were crystallized to form orthorhombic SrZrO3. SrZrO3 particles exhibited non-agglomerated hollow spherical morphology with an average particle size of 300 nm. The UV-excited photoluminescence spectrum of SrZrO3:Eu(3+) consisted of two regions. One region was associated with SrZrO3 trap emission, and the other one was related to the emission of Eu(3+) ions. The intensity ratio of the emission of Eu(3+) ions to the host emission (FIR) and the emission lifetime of Eu(3+) ions were measured in the temperature range of 300-550 K. The sensitivity obtained via the lifetime method was 7.3* lower than that measured via the FIR. Within the optimum temperature range of 300-460 K, the as-estimated sensor sensitivity was increased from 0.0013 to 0.028 K(-1). With a further increase in temperatures, the sensitivity started to decline. A maximum relative sensitivity was estimated to be 2.22%K(-1) at 460 K. The resolutions in both methods were below 1K in the above temperature range. The results indicated the suitability of SrZrO3:Eu(3+) for the distinct high temperature sensing applications. PMID- 27189118 TI - New natural products isolated from Metarhizium robertsii ARSEF 23 by chemical screening and identification of the gene cluster through engineered biosynthesis in Aspergillus nidulans A1145. AB - To rapidly identify novel natural products and their associated biosynthetic genes from underutilized and genetically difficult-to-manipulate microbes, we developed a method that uses (1) chemical screening to isolate novel microbial secondary metabolites, (2) bioinformatic analyses to identify a potential biosynthetic gene cluster and (3) heterologous expression of the genes in a convenient host to confirm the identity of the gene cluster and the proposed biosynthetic mechanism. The chemical screen was achieved by searching known natural product databases with data from liquid chromatographic and high resolution mass spectrometric analyses collected on the extract from a target microbe culture. Using this method, we were able to isolate two new meroterpenes, subglutinols C (1) and D (2), from an entomopathogenic filamentous fungus Metarhizium robertsii ARSEF 23. Bioinformatics analysis of the genome allowed us to identify a gene cluster likely to be responsible for the formation of subglutinols. Heterologous expression of three genes from the gene cluster encoding a polyketide synthase, a prenyltransferase and a geranylgeranyl pyrophosphate synthase in Aspergillus nidulans A1145 afforded an alpha-pyrone fused uncyclized diterpene, the expected intermediate of the subglutinol biosynthesis, thereby confirming the gene cluster to be responsible for the subglutinol biosynthesis. These results indicate the usefulness of our methodology in isolating new natural products and identifying their associated biosynthetic gene cluster from microbes that are not amenable to genetic manipulation. Our method should facilitate the natural product discovery efforts by expediting the identification of new secondary metabolites and their associated biosynthetic genes from a wider source of microbes. PMID- 27189119 TI - Efficacy of ampicillin against methicillin-resistant Staphylococcus aureus restored through synergy with branched poly(ethylenimine). AB - beta-Lactam antibiotics kill Staphylococcus aureus bacteria by inhibiting the function of cell wall penicillin-binding proteins (PBPs) 1 and 3. However, beta lactams are ineffective against PBP2a, used by methicillin-resistant S. aureus (MRSA) to perform essential cell wall crosslinking functions. PBP2a requires teichoic acid to properly locate and orient the enzyme, and thus MRSA is susceptible to antibiotics that prevent teichoic acid synthesis in the bacterial cytoplasm. As an alternative, we have used branched poly(ethylenimine), BPEI, to target teichoic acid in the bacterial cell wall. The result is restoration of MRSA susceptibility to the beta-lactam antibiotic ampicillin with a MIC of 1 MUg ml-1, superior to that of vancomycin (MIC=3.7 MUg ml-1). A checkerboard assay shows synergy of BPEI and ampicillin. NMR data show that BPEI alters the teichoic acid chemical environment. Laser scanning confocal microscopy images show BPEI residing on the bacterial cell wall, where teichoic acids and PBPs are located. PMID- 27189121 TI - Antibacterial activity of the novel semisynthetic lantibiotic NVB333 in vitro and in experimental infection models. AB - NVB333 is a novel semisynthetic lantibiotic derived from the amide coupling of 3,5-dichlorobenzylamine to the C-terminal of deoxyactagardine B. The in vitro activity of NVB333 includes efficacy against clinically relevant pathogens including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus spp. NVB333 shows no cross-resistance with other antibiotics tested and a very low propensity for resistance development. After intravenous dosing NVB333 has high exposure in mouse plasma and shows generally improved in vivo activity compared with vancomycin in mouse infection models despite modest MIC values. In thigh infection models, promising efficacy was demonstrated against several strains of S. aureus including methicillin-resistant S. aureus (MRSA) and vancomycin-intermediate S. aureus (VISA) strains, and against Enterococcus faecalis UNT126-3. Area under the concentration curve (AUC)/MIC was shown to be the best predictor of efficacy against S. aureus UNT103-3 with an AUC/MIC of 138 (uncorrected for protein binding) achieving a static effect. NVB333 was also effective in a disseminated infection model where it conferred complete survival from the MRSA strain ATCC 33591. NVB333 showed rather modest lung penetration after intravenous dosing (AUC in lung 2-3% of plasma AUC), but because of very high plasma exposure, therapeutic levels of compound were achieved in the lung. Efficacy at least equal to vancomycin was demonstrated against an MRSA strain (UNT084-3) in a bronchoalveolar infection model. The impressive in vivo efficacy of NVB333 and strong resistance prognosis makes this compound an interesting candidate for development for treating systemic Gram-positive infections. PMID- 27189122 TI - Preclinical development of Ramizol, an antibiotic belonging to a new class, for the treatment of Clostridium difficile colitis. AB - Antibiotic-resistant bacteria is a major threat to human health and is predicted to become the leading cause of death from disease by 2050. Despite the recent resurgence of research and development in the area, few antibiotics have reached the market, with most of the recently approved antibiotics corresponding to new uses for old antibiotics, or structurally similar derivatives thereof. We have recently reported an in silico approach that led to the design of an entirely new class of antibiotics for the bacteria-specific mechanosensitive ion channel of large conductance: MscL. Here, we present the preclinical development of one such antibiotic, Ramizol, a first generation antibiotic belonging to that class. We present the lack of interaction between Ramizol and other mammalian channels adding credibility to its MscL selectivity. We determine the pharmacokinetic profile in a rat model and show <0.1% of Ramizol is absorbed systemically. We show this non-systemic nature of the antibiotic translates to over 70% survival of hamsters in a Clostridium difficile colitis model. Lastly, initial in vitro data indicate that resistance to Ramizol occurs at a low frequency. In conclusion, we establish the potential of Ramizol as an effective new treatment for C. difficile associated disease. PMID- 27189120 TI - Design, synthesis and microbiological evaluation of ampicillin-tetramic acid hybrid antibiotics. AB - Exploiting iron-uptake pathways by conjugating beta-lactam antibiotics with iron chelators, such as catechol and hydroxamic acid is a proven strategy to overcome permeability-related resistance in Gram-negative bacteria. As naturally occurring iron-chelating tetramic acids have not been previously examined for this purpose, an exploratory series of novel ampicillin-tetramic acid hybrids that structurally resemble ureidopenicillins was designed and synthesized. The new analogs were evaluated for the ability to chelate iron and their MIC activities determined against a representative panel of clinically significant bacterial pathogens. The tetramic acid beta-lactam hybrids demonstrated a high affinity to iron in the order of 10-30 M3. The hybrids were less active against Gram-positive bacteria. However, against Gram-negative bacteria, their activity was species dependent with several hybrids displaying improved activity over ampicillin against wild type Pseudomonas aeruginosa. The anti-Gram-negative activities of the hybrids improved in the presence of clavulanic acid revealing that the tetramic acid moiety did not provide added protection against beta-lactamases. In addition, the hybrids were found to be efflux pump substrates as their activities markedly improved against pump-inactivated strains. Unlike the catechol and hydroxamic acid siderophore beta-lactam conjugates, the activities of the hybrids did not improve under iron-deficient conditions. These results suggest that the tetramic acid hybrids gain permeability via different membrane receptors, or they are outcompeted by native bacterial siderophores with stronger affinities for iron. This study provides a foundation for the further exploitation of the tetramic acid moiety to achieve novel beta-lactam anti-Gram-negative agents, providing that efflux and beta-lactamase mediated resistance is addressed. PMID- 27189123 TI - Quinovosamycins: new tunicamycin-type antibiotics in which the alpha, beta-1",11' linked N-acetylglucosamine residue is replaced by N-acetylquinovosamine. AB - Tunicamycins (TUN) are potent inhibitors of polyprenyl phosphate N acetylhexosamine 1-phosphate transferases (PPHP), including essential eukaryotic GPT enzymes and bacterial HexNAc 1-P translocases. Hence, TUN blocks the formation of eukaryotic N-glycoproteins and the assembly of bacterial call wall polysaccharides. The genetic requirement for TUN production is well-established. Using two genes unique to the TUN pathway (tunB and tunD) as probes we identified four new prospective TUN-producing strains. Chemical analysis showed that one strain, Streptomyces niger NRRL B-3857, produces TUN plus new compounds, named quinovosamycins (QVMs). QVMs are structurally akin to TUN, but uniquely in the 1",11'-HexNAc sugar head group, which is invariably d-GlcNAc for the known TUN, but is d-QuiNAc for the QVM. Surprisingly, this modification has only a minor effect on either the inhibitory or antimicrobial properties of QVM and TUN. These findings have unexpected consequences for TUN/QVM biosynthesis, and for the specificity of the PPHP enzyme family. PMID- 27189125 TI - [Suppression of sexual activity and reproduction in male small ruminants]. AB - Handling and husbandry of male small ruminants after sexual maturity often become difficult. Castration is currently the most reliable solution to this problem. Medicinal procedures for temporary inhibition of the gonad function could provide an alternative. Following a short overview of surgical castration, the current knowledge on the application of vaccines against gonadotropin-releasing hormone (GnRH) and GnRH agonist in rams and billy goats is presented in a literature overview. In rams, GnRH vaccination has been used successfully for temporary suppression of the reproduction function, regardless of an animal's age at the time of therapy initiation. Fewer investigations are available for the billy goat. A complete suppression of spermatogenesis was not achieved in all cases. Currently, treatment with GnRH agonists does not represent a relible method for the suppression of gonad function. PMID- 27189124 TI - Using quantum chemical computations of NMR chemical shifts to assign relative configurations of terpenes from an engineered Streptomyces host. AB - Density functional theory calculations of (1)H and (13)C chemical shifts are used to assign the relative configurations of isohirsut-1-ene, isohirsut-4-ene and tsukubadiene, three terpenes previously isolated from an engineered Streptomyces. PMID- 27189126 TI - An investigation of factors related to the use of respite care services for children with severe motor and intellectual disabilities (SMID) living at home in Japan. AB - Limited time away from the child is cited as the main factor that increases the burden for the primary caregiver of severely disabled children. The aim of this study was to quantitatively elucidate the factors related to the desire to use social services and the actual use of respite care services by the primary caregivers of severely disabled children in Japan. In this study, we investigated the use of respite care services in accordance with the primary caregivers' wishes by examining inhibiting or promoting factors associated with respite care service use only among those who wished to use social services. A total of 169 Japanese mothers participated and answered the questionnaires. We conducted a logistic regression analysis and a multiple regression analysis to investigate the factors related to respite care service use. The most important factors affecting a primary caregiver's desire to use social services were the belief that the child would enjoy using social services and the family's approval of the social service use. The most important factors affecting respite care service use were the family's approval of the use and a large care burden on the primary caregiver. Respite care services should be sought out before the care burden becomes too great to enable the primary caregiver to more easily contribute to the continuation of home care. A background of mother-child separation anxiety disrupted the use of respite care. However, believing that the child enjoys using social services may reduce primary caregivers' psychological resistance to being separated from their child, which is supported by tradition. Thus, it is also important for respite care service providers to provide information about the children to their primary caregivers and families while they are using respite care services. PMID- 27189128 TI - Corrigendum: Facile Aluminum Reduction Synthesis of Blue TiO2 with Oxygen Deficiency for Lithium-Ion Batteries. PMID- 27189129 TI - Spotlights on our sister journals: Chem. Eur. J. 22/2016. PMID- 27189127 TI - Seroprevalence and risk factors of infections with Neospora caninum and Toxoplasma gondii in hunting dogs from Campania region, southern Italy. AB - Hunting dogs have probably a higher level of exposure to Neospora caninum Dubey, Carpenter, Speer, Topper et Uggla, 1988 and Toxoplasma gondii Nicolle et Manceaux, 1908 than other canine populations for their different lifestyle. The aim of our survey was to determine the seroprevalence of N. caninum and T. gondii in hunting dogs from southern Italy and assess risk factors related to these protozoan infections. Blood samples were collected from 398 hunting dogs (19 different breeds, aged from 5 month to 14 years). The sera were screened by indirect fluorescence antibody test; a titre >= 50 was considered positive. Antibodies to N. caninum and T. gondii were detected in 59 (15%) dogs with titres from 50 to 3 200 and in 94 (24%) dogs with titres from 50 to 1 600, respectively, with co-infection in 25 (6%) dogs. Statistical difference (p <= 0.05) was found only for infection with T. gondii between two age groups: >= 2-4 years (16%) and >= 4-7 years (33%); other observed characteristics were without statistical significance. Our results suggest that the hunting dogs could play an important role in the transmission cycle of N. caninum between wild animals and livestock. This is the first detection of antibodies to T. gondii in hunting dogs in Italy. PMID- 27189130 TI - Venous thrombosis. AB - Venous thromboembolism (VTE) encompasses deep-vein thrombosis (DVT) and pulmonary embolism. VTE is the leading cause of lost disability-adjusted life years and the third leading cause of cardiovascular death in the world. DVT leads to post thrombotic syndrome, whereas pulmonary embolism can cause chronic pulmonary hypertension, both of which reduce quality of life. Genetic and acquired risk factors for thrombosis include non-O blood groups, factor V Leiden mutation, oral contraceptive use, hormone replacement therapy, advanced age, surgery, hospitalization and long-haul travel. A combination of blood stasis, plasma hypercoagulability and endothelial dysfunction is thought to trigger thrombosis, which starts most often in the valve pockets of large veins. Animal studies have revealed pathogenic roles for leukocytes, platelets, tissue factor-positive microvesicles, neutrophil extracellular traps and factors XI and XII. Diagnosis of VTE requires testing and exclusion of other pathologies, and typically involves laboratory measures (such as D-dimer) and diagnostic imaging. VTE is treated with anticoagulants and occasionally with thrombolytics to prevent thrombus extension and to reduce thrombus size. Anticoagulants are also used to reduce recurrence. New therapies with improved safety profiles are needed to prevent and treat venous thrombosis. For an illustrated summary of this Primer, visit: http://go.nature.com/8ZyCuY. PMID- 27189131 TI - Large-area high-quality graphene on Ge(001)/Si(001) substrates. AB - Various experimental data revealing large-area high-quality graphene films grown by the CVD method on Ge(001)/Si(001) substrates are presented. SEM images have shown that the structure of nano-facets is formed on the entire surface of Ge(001), which is covered by a graphene layer over the whole macroscopic sample surface of 1 cm(2). The hill-and-valley structures are positioned 90 degrees to each other and run along the <100> direction. The hill height in relation to the valley measured by STM is about 10 nm. Raman measurements have shown that a uniform graphene monolayer covers the nano-facet structures on the Ge(001) surface. Raman spectroscopy has also proved that the grown graphene monolayer is characterized by small strain variations and minimal charge fluctuations. Atomically resolved STM images on the hills of the nanostructures on the Ge(001) surface have confirmed the presence of a graphene monolayer. In addition, the STS/CITS maps show that high-quality graphene has been obtained on such terraces. The subsequent coalescence of graphene domains has led to a relatively well oriented large-area layer. This is confirmed by LEED measurements, which have indicated that two orientations are preferable in the grown large-area graphene monolayer. The presence of large-area coverage by graphene has been also confirmed by low temperature Hall measurements of a macroscopic sample, showing an n-type concentration of 9.3 * 10(12) cm(-2) and a mobility of 2500 cm(2) V(-1) s(-1). These important characteristic features of graphene indicate a high homogeneity of the layer grown on the large area Ge(001)/Si(001) substrates. PMID- 27189132 TI - A Meta-Analysis of the Association of Chronic Obstructive Pulmonary Disease with Abdominal Aortic Aneurysm Presence. AB - BACKGROUND: Several case-control and population-based abdominal aortic aneurysm (AAA) screening studies have reported inconclusive results of the association of chronic obstructive pulmonary disease (COPD) with AAA presence. To determine whether COPD is associated with AAA presence, we performed a meta-analysis of contemporary clinical studies. METHODS: To identify all contemporary case-control and population-based AAA screening studies evaluating the association of COPD with AAA presence, databases including MEDLINE and EMBASE were searched from January 2000 to May 2015 using Web-based search engines (PubMed and OVID). An adjusted odds ratio (OR) and 95% confidence intervals (CI) for COPD or AAA presence (using multivariable logistic regression) were abstracted from each individual study. We took an OR for AAA presence to be representative of an OR for COPD presence. RESULTS: Of 159 potentially relevant articles screened initially, there were 7 case-control and 4 population-based AAA screening studies that met eligibility requirements and were included. Pooled analysis of all the 11 studies (14 estimates, 155,731 participants), 7 case-control studies (4171 participants), and 4 population-based AAA screening studies (7 estimates, 151,560 participants) respectively demonstrated a statistically significant 1.78-fold (OR 1.78, 95% CI 1.38-2.30, P < 0.00001), 3.05-fold (OR 3.05, 95% CI 1.44-6.49, P = 0.004), and 1.24-fold (OR 1.24, 95% CI 1.04-1.48, P = 0.02) increased prevalence/incidence of COPD in patients with AAA relative to subjects without AAA (i.e., a statistically significant 1.78-, 3.05-, and 1.24-fold increased prevalence/incidence of AAA in patients with COPD relative to subjects without COPD) (P for subgroup differences = 0.02). CONCLUSION: The present meta-analysis demonstrated 1.8-fold increased prevalence/incidence of COPD in patients with AAA relative to subjects without AAA (i.e., 1.8-fold increased prevalence/incidence of AAA in patients with COPD relative to subjects without COPD), which suggests that COPD is associated with AAA presence. PMID- 27189133 TI - Neutrophils extracellular traps damage Naegleria fowleri trophozoites opsonized with human IgG. AB - Naegleria fowleri infects humans through the nasal mucosa causing a disease in the central nervous system known as primary amoebic meningoencephalitis (PAM). Polymorphonuclear cells (PMNs) play a critical role in the early phase of N. fowleri infection. Recently, a new biological defence mechanism called neutrophil extracellular traps (NETs) has been attracting attention. NETs are composed of nuclear DNA combined with histones and antibacterial proteins, and these structures are released from the cell to direct its antimicrobial attack. In this work, we evaluate the capacity of N. fowleri to induce the liberation of NETs by human PMN cells. Neutrophils were cocultured with unopsonized or IgG-opsonized N. fowleri trophozoites. DNA, histone, myeloperoxidase (MPO) and neutrophil elastase (NE) were stained, and the formation of NETs was evaluated by confocal microscopy and by quantifying the levels of extracellular DNA. Our results showed N. fowleri induce the liberation of NETs including release of MPO and NE by human PMN cells as exposure interaction time is increased, but N. fowleri trophozoites evaded killing. However, when trophozoites were opsonized, they were susceptible to the neutrophils activity. Therefore, our study suggests that antibody-mediated PMNs activation through NET formation may be crucial for antimicrobial responses against N. fowleri. PMID- 27189134 TI - 3D scanning and 3D printing as innovative technologies for fabricating personalized topical drug delivery systems. AB - Acne is a multifactorial inflammatory skin disease with high prevalence. In this work, the potential of 3D printing to produce flexible personalised-shape anti acne drug (salicylic acid) loaded devices was demonstrated by two different 3D printing (3DP) technologies: Fused Deposition Modelling (FDM) and stereolithography (SLA). 3D scanning technology was used to obtain a 3D model of a nose adapted to the morphology of an individual. In FDM 3DP, commercially produced Flex EcoPLATM (FPLA) and polycaprolactone (PCL) filaments were loaded with salicylic acid by hot melt extrusion (HME) (theoretical drug loading - 2% w/w) and used as feedstock material for 3D printing. Drug loading in the FPLA salicylic acid and PCL-salicylic acid 3D printed patches was 0.4% w/w and 1.2% w/w respectively, indicating significant thermal degradation of drug during HME and 3D printing. Diffusion testing in Franz cells using a synthetic membrane revealed that the drug loaded printed samples released <187MUg/cm(2) within 3h. FPLA-salicylic acid filament was successfully printed as a nose-shape mask by FDM 3DP, but the PCL-salicylic acid filament was not. In the SLA printing process, the drug was dissolved in different mixtures of poly(ethylene glycol) diacrylate (PEGDA) and poly(ethylene glycol) (PEG) that were solidified by the action of a laser beam. SLA printing led to 3D printed devices (nose-shape) with higher resolution and higher drug loading (1.9% w/w) than FDM, with no drug degradation. The results of drug diffusion tests revealed that drug diffusion was faster than with the FDM devices, 229 and 291MUg/cm(2) within 3h for the two formulations evaluated. In this study, SLA printing was the more appropriate 3D printing technology to manufacture anti-acne devices with salicylic acid. The combination of 3D scanning and 3D printing has the potential to offer solutions to produce personalised drug loaded devices, adapted in shape and size to individual patients. PMID- 27189136 TI - Nasal immunization with mannan-decorated mucoadhesive HPMCP microspheres containing ApxIIA toxin induces protective immunity against challenge infection with Actinobacillus pleuropneumoiae in mice. AB - The development of subunit mucosal vaccines requires an appropriate delivery system or an immune modulator such as an adjuvant to improve antigen immunogenicity. The nasal route for vaccine delivery by microparticles has attracted considerable interest, although challenges such as the rapid mucociliary clearance in the respiratory mucosa and the low immunogenicity of subunit vaccine still remain. Here, we aimed to develop mannan-decorated mucoadhesive thiolated hydroxypropylmethyl cellulose phthalate (HPMCP) microspheres (Man-THM) that contain ApxIIA subunit vaccine - an exotoxin fragment as a candidate for a subunit nasal vaccine against Actinobacillus pleuropneumoniae. For adjuvant activity, mucoadhesive thiolated HPMCP microspheres decorated with mannan could be targeted to the PRRs (pathogen recognition receptors) and mannose receptors (MR) of antigen presenting cells (APCs) in the respiratory immune system. The potential adjuvant ability of Man THM for intranasal immunization was confirmed by in vitro and in vivo experiments. In a mechanistic study using APCs in vitro, it was found that Man THM enhanced receptor-mediated endocytosis by stimulating the MR of APCs. In vivo, the nasal vaccination of ApxIIA-loaded Man-THM in mice resulted in higher levels of mucosal sIgA and serum IgG than mice in the ApxIIA and ApxIIA-loaded THM groups due to the specific recognition of the mannan in the Man-THM by the MRs of the APCs. Moreover, ApxIIA-containing Man-THM protected immunized mice when challenged with strains of A. pleuropneumoniae serotype 5. These results suggest that mucoadhesive Man-THM may be a promising candidate for a nasal vaccine delivery system to elicit systemic and mucosal immunity that can protect from pathogenic bacteria infection. PMID- 27189135 TI - Overcoming multidrug resistance in Dox-resistant neuroblastoma cell lines via treatment with HPMA copolymer conjugates containing anthracyclines and P-gp inhibitors. AB - Water-soluble N-(2-hydroxypropyl)methacrylamide copolymer conjugates bearing the anticancer drugs doxorubicin (Dox) or pirarubicin (THP), P-gp inhibitors derived from reversin 121 (REV) or ritonavir (RIT)), or both anticancer drug and P-gp inhibitor were designed and synthesized. All biologically active molecules were attached to the polymer carrier via pH-sensitive spacer enabling controlled release in mild acidic environment modeling endosomes and lysosomes of tumor cells. The cytotoxicity of the conjugates against three sensitive and Dox resistant neuroblastoma (NB) cell lines, applied alone or in combination, was studied in vitro. All conjugates containing THP displayed higher cytotoxicity against all three Dox-resistant NB cell lines compared with the corresponding Dox containing conjugates. Furthermore, the cytotoxicity of conjugates containing both drug and P-gp inhibitor was up to 10 times higher than that of the conjugate containing only drug. In general, the polymer-drug conjugates showed higher cytotoxicity when conjugates containing inhibitors were added 8 or 16h prior to treatment compared with conjugates bearing both the inhibitor and the drug. The difference in cytotoxicity was more pronounced at the 16-h time point. Moreover, higher inhibitor:drug ratios resulted in higher cytotoxicity. The cytotoxicity of the polymer-drug used in combination with polymer P-gp inhibitor was up to 84 times higher than that of the polymer-drug alone. PMID- 27189137 TI - Transplantation of testicular tissue in alginate hydrogel loaded with VEGF nanoparticles improves spermatogonial recovery. AB - Transplantation of cryopreserved immature testicular tissue (ITT) is a promising strategy to restore fertility in young boys facing gonadotoxic treatments. However, up to now, limited spermatogonial recovery has been achieved in xenografting models used to evaluate the potential of cryopreserved tissue transplantation. When comparing avascular xenografts of cryopreserved and fresh human ITT into a mouse model, the number of spermatogonia was significantly reduced, regardless of the cryopreservation procedure used. To improve tissue engraftment, revascularization and hence spermatogonial survival, ITT was embedded in two types of hydrogel loaded with VEGF nanoparticles. Small pieces (+/-1mm(3)) of testicular tissue were grafted in NMRI mice as follows: grafted without encapsulation, grafted after encapsulation in fibrin, in alginate, in fibrin-VEGF-nanoparticle (NP) and in alginate-VEGF-NP. Non-grafted tissue served as control. After 5 and 21days of implantation, seminiferous tubule integrity, revascularization and spermatogonial recovery were evaluated by histology and immunohistochemistry. Seminiferous tubule integrity ranged from 13.3% to 39.6% and 42.7% to 68.7% on day 5 and day 21, respectively. Vascular density on day 5 was found to be higher in VEGF supplemented groups, regardless of the hydrogel used. Staining for phosphorylated VEGF receptor 2 and endothelial proliferation on day 5 was higher in all groups compared to non-grafted avascular controls. Spermatogonial recovery ranged between 14.8% and 27.3% on day 21 and was significantly higher in the alginate and alginate-VEGF-NP groups. The present study demonstrates the potential of alginate hydrogel loaded with nanoencapsulated growth factors to improve cryopreserved tissue engraftment. PMID- 27189138 TI - Comprehensive characterisation of sewage sludge for thermochemical conversion processes - Based on Singapore survey. AB - Recently, sludge attracted great interest as a potential feedstock in thermochemical conversion processes. However, compositions and thermal degradation behaviours of sludge were highly complex and distinctive compared to other traditional feedstock led to a need of fundamental research on sludge. Comprehensive characterisation of sludge specifically for thermochemical conversion was carried out for all existing Water Reclamation Plants in Singapore. In total, 14 sludge samples collected based on the type, plant, and batch categorisation. Existing characterisation methods for physical and chemical properties were analysed and reviewed using the collected samples. Qualitative similarities and quantitative variations of different sludge samples were identified and discussed. Oxidation of inorganic in sludge during ash forming analysis found to be causing significant deviations on proximate and ultimate analysis. Therefore, alternative parameters and comparison basis including Fixed Residues (FR), Inorganic Matters (IM) and Total Inorganics (TI) were proposed for better understanding on the thermochemical characteristics of sludge. PMID- 27189139 TI - The effect of composting on the persistence of four ionophores in dairy manure and poultry litter. AB - Manure composting is a well-described approach for stabilization of nutrients and reduction of pathogens and odors. Although composting studies have shown that thermophilic temperatures and aerobic conditions can increase removal rates of selected antibiotics, comparable information is lacking for many other compounds in untreated or composted manure. The objective of this study was to determine the relative effectiveness of composting conditions to reduce concentrations of four widely used ionophore feed supplements in dairy manure and poultry litter. Replicate aliquots of fresh poultry litter and dairy manure were amended with monensin, lasalocid, salinomycin, or amprolium to 10mgkg(-1)DW. Non-amended and amended dairy manure and poultry litter aliquots were incubated at 22, 45, 55, or 65 degrees C under moist, aerobic conditions. Residue concentrations were determined from aliquots removed after 1, 2, 4, 6, 8, and 12weeks. Results suggest that the effectiveness of composting for contaminant reduction is compound and matrix specific. Composting temperatures were not any more effective than ambient temperature in increasing the rate or extent of monensin removal in either poultry litter or dairy manure. Composting was effective for lasalocid removal in poultry litter, but is likely to be too slow to be useful in practice (8-12weeks at 65 degrees C for >90% residue removal). Composting was effective for amprolium removal from poultry litter and salinomycin in dairy manure but both required 4-6weeks for >90% removal. However, composting did not increase the removal rates or salinomycin in poultry litter or the removal rates of lasalocid or amprolium in dairy manure. PMID- 27189140 TI - Phase-reference monitoring in coherent-state discrimination assisted by a photon number resolving detector. AB - Phase estimation represents a crucial challenge in many fields of Physics, ranging from Quantum Metrology to Quantum Information Processing. This task is usually pursued by means of interferometric schemes, in which the choice of the input states and of the detection apparatus is aimed at minimizing the uncertainty in the estimation of the relative phase between the inputs. State discrimination protocols in communication channels with coherent states also require the monitoring of the optical phase. Therefore, the problem of phase estimation is relevant to face the issue of coherent states discrimination. Here we consider a quasi-optimal Kennedy-like receiver, based on the interference of two coherent signals, to be discriminated, with a reference local oscillator. By means of the Bayesian processing of a small amount of data drawn from the outputs of the shot-by-shot discrimination protocol, we demonstrate the achievement of the minimum uncertainty in phase estimation, also in the presence of uniform phase noise. Moreover, we show that the use of photon-number resolving detectors in the receiver improves the phase-estimation strategy, especially with respect to the usually employed on/off detectors. From the experimental point of view, this comparison is realized by employing hybrid photodetectors. PMID- 27189141 TI - Systemic sclerosis. AB - Systemic sclerosis is a complex autoimmune disease characterized by a chronic and frequently progressive course and by extensive patient-to-patient variability. Like other autoimmune diseases, systemic sclerosis occurs more frequently in women, with a peak of onset in the fifth decade of life. The exact cause of systemic sclerosis remains elusive but is likely to involve environmental factors in a genetically primed individual. Pathogenesis is dominated by vascular changes; evidence of autoimmunity with distinct autoantibodies and activation of both innate and adaptive immunity; and fibrosis of the skin and visceral organs that results in irreversible scarring and organ failure. Intractable progression of vascular and fibrotic organ damage accounts for the chronic morbidity and high mortality. Early and accurate diagnosis and classification might improve patient outcomes. Screening strategies facilitate timely recognition of life-threatening complications and initiation of targeted therapies to halt their progression. Effective treatments of organ-based complications are now within reach. Discovery of biomarkers - including autoantibodies that identify patient subsets at high risk for particular disease complications or rapid progression - is a research priority. Understanding the key pathogenetic pathways, cell types and mediators underlying disease manifestations opens the door for the development of targeted therapies with true disease-modifying potential. For an illustrated summary of this Primer, visit: http://go.nature.com/lchkcA. PMID- 27189142 TI - Direction to an Internet Support Group Compared With Online Expressive Writing for People With Depression And Anxiety: A Randomized Trial. AB - BACKGROUND: Depression and anxiety are common, often comorbid, conditions, and Internet support groups for them are well used. However, little rigorous research has been conducted on the outcome of these groups. OBJECTIVE: This study aimed to evaluate the efficacy of an Internet support group in reducing depression and anxiety, and increasing social support and life satisfaction. METHODS: A randomized trial compared direction to an existing Internet support group for depression and anxiety with an online expressive writing condition. A total of 863 (628 female) United Kingdom, United States, and Canadian volunteers were recruited via the Internet. Online, self-report measures of depression, anxiety, social support, and satisfaction with life were administered at baseline, 3, and 6 months. RESULTS: All four outcomes - depression, anxiety, social support, and satisfaction with life - improved over the 6 months of the study (all P <.001). There was no difference in outcome between the two conditions: participants responded similarly to the expressive writing and the Internet support group. Engagement with the Internet support group was low, it had high 6-month attrition (692/795, 87%) and low adherence, and it received mixed and often negative feedback. The main problems reported were a lack of comfort and connection with others, negative social comparisons, and the potential for receiving bad advice. Expressive writing had lower attrition (194/295, 65%) and participants reported that it was more acceptable. CONCLUSIONS: Until further evidence accumulates, directing people with depression and anxiety to Internet support groups cannot be recommended. On the other hand, online expressive writing seems to have potential, and its use for people with depression and anxiety warrants further investigation. TRIAL REGISTRATION: TRIAL REGISTRATION: Clinicaltrials.gov NCT01149265; https://clinicaltrials.gov/ct2/show/NCT01149265 (Archived by WebCite at http://www.webcitation.org/6hYISlNFT). PMID- 27189143 TI - Cytotoxic trans-platinum(II) complex with 3-hydroxymethylpyridine: Synthesis, X ray structure and biological activity evaluation. AB - To assess the potential cytostatic properties of Pt(II) complexes with 3 hydroxymethylpyridine (3-hmpy) as the only carrier ligand, novel cis-[PtCl2(3 hmpy)2] (1) and trans-[PtCl2(3-hmpy)2] (2) have been prepared. Elemental analysis, FTIR spectroscopy, multinuclear NMR spectroscopy and X-ray crystallography were used to determine their structures. Based on the results obtained with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay and clonogenic assay on T24 human bladder carcinoma cells (T24), the most potent compound 2 was further tested for cytotoxicity in human ovarian carcinoma cell lines - cisplatin sensitive (IGROV 1) and its resistant subclone (IGROV 1/RDDP). The cytotoxicity of compound 2 in IGROV 1/RDDP is comparable to cisplatin. Furthermore, compound 2 induced severe conformational changes in plasmid DNA, which resulted in a delayed onset of apoptosis in T24 cells, and higher amounts of Pt in tumours and serum compared to cisplatin. In addition, in vivo antitumour effectiveness was comparable to that of cisplatin with a smaller reduction of animals' body weight, thus demonstrating that it is a promising transplatin analogue which deserves further studies. PMID- 27189144 TI - Protective behavioural strategies while drinking: do they protect against sexual victimisation and is this protection gendered? AB - INTRODUCTION AND AIMS: Although alcohol use has been linked to sexual victimisation among college students , the specific ways in which college students may be able to avoid the negative consequences of excessive drinking as they relate to sexual victimisation have not been fully explored. This study examines whether using protective behavioural strategies attenuates the risk of sexual victimisation for both male and female college students and whether this relationship is moderated by alcohol use. DESIGN AND METHOD: Data were obtained from the Fall 2012 National College Health Assessment Survey. This survey is conducted on college campuses across the USA and institutions that self-selected to participate in the survey. The sample used in the study includes 19 881 students (male and female) across 51 schools. RESULTS: Findings indicate that although women are more likely to use protective behavioural strategies, these strategies work to reduce the likelihood of experiencing sexual victimisation for both sexes among those who are high-frequency drinkers. DISCUSSION AND CONCLUSIONS: This study suggests that the frequency of alcohol use is important when considering the risk of sexual victimisation among college students, and protective behavioural strategies can help reduce this risk among frequent drinkers. [Daigle LE, Johnson LM, Napper SL, Azimi AM. Protective behavioural strategies while drinking: do they protect against sexual victimisation and is this protection gendered?. Drug Alcohol Rev 2016;35:573-579]. PMID- 27189145 TI - Zinc isotope ratios of bones and teeth as new dietary indicators: results from a modern food web (Koobi Fora, Kenya). AB - In order to explore the possibilities of using zinc (Zn) stable isotope ratios as dietary indicators, we report here on the measurements of the ratio of stable isotopes of zinc ((66)Zn/(64)Zn, expressed here as delta(66)Zn) in bioapatite (bone and dental enamel) of animals from a modern food web in the Koobi Fora region of the Turkana Basin in Kenya. We demonstrate that delta(66)Zn values in both bone and enamel allow a clear distinction between carnivores and herbivores from this food web. Differences were also observed between browsers and grazers as well as between carnivores that consumed bone (i.e. hyenas) compared to those that largely consume flesh (i.e. lions). We conclude that Zn isotope ratio measurements of bone and teeth are a new and promising dietary indicator. PMID- 27189146 TI - Clarity in the face of confusion: new studies tip the scales on bisphenol A (BPA). PMID- 27189147 TI - Cushing's disease: the burden of illness. AB - Cushing's syndrome is caused by prolonged exposure to elevated cortisol levels. The most common form of endogenous Cushing's syndrome is Cushing's disease, which results from an adrenocorticotropic hormone-secreting pituitary tumour. Cushing's disease is associated with increased mortality, mostly attributable to cardiovascular complications, and a host of comorbidities such as metabolic and skeletal disorders, infections and neuropsychiatric disturbances. As a consequence, Cushing's disease substantially impairs health-related quality of life. It is crucial that the condition is diagnosed as early as possible, and that rapid and effective treatment is initiated in order to limit long-term morbidity and mortality. The initial treatment of choice for Cushing's disease is selective transsphenoidal pituitary surgery; however, the risk of recurrence after initial surgery is high and remains so for many decades after surgery. A particular concern is the growing body of evidence indicating that the negative physical and psychosocial sequelae of chronic hypercortisolism may persist in patients with Cushing's disease even after long-term surgical 'cure'. Current treatment options for post-surgical patients with persistent or recurrent Cushing's disease include second surgery, radiotherapy, bilateral adrenalectomy and medical therapy; however, each approach has its limitations and there is an unmet need for more efficacious treatments. The current review provides an overview of the burden of illness of Cushing's disease, underscoring the need for prompt diagnosis and effective treatment, as well as highlighting the need for better therapies. PMID- 27189148 TI - Serial post-surgical stimulated and unstimulated highly sensitive thyroglobulin measurements in low- and intermediate-risk papillary thyroid carcinoma patients not receiving radioactive iodine. AB - The purpose of this study was to determine the natural temporal trends of serial thyroglobulin (Tg) among low/intermediate-risk PTC patients not receiving radioactive iodine (RAI) using TSH-stimulated Tg (Stim-Tg) and unstimulated highly sensitive Tg (u-hsTg). We prospectively analyzed serial Stim-Tg measurements after total thyroidectomy +/- therapeutic central neck dissection among 121 consecutive low/intermediate-risk PTC patients who did not receive RAI, of whom 104 also had serial u-hsTg measurements available. Median follow-up was 6.5 years with Stim-Tg measurements commencing 3 months after surgery and u-hsTg commencing 1.8 years after surgery (when the assay became available). TSH stimulation was performed with 9-day T3 withdrawal, 22-day T4 withdrawal, or using recombinant human TSH (rhTSH). To account for within-patient correlations of repeated Tg measurements, temporal trends in Stim-Tg and u-hsTg were assessed using Generalized Estimating Equations. Stim-Tg models were adjusted for the method of TSH stimulation, whereas the u-hsTg models were adjusted for concurrent TSH level. Linear regression modeling was used to assess the trend in serial Stim Tg and u-hsTg measurements as a function time from time of surgery throughout the duration of follow-up. The main outcome measured was the change in u-hsTg and Stim-Tg measurements over time. A total of 337 Stim-Tg (2.8/patient) and 602 u hsTg (5.8/patient) measurements were analyzed. Among the 337 Stim-Tg measurements, Stim-Tg was assessed using rhTSH in 202 (60 %), T4 withdrawal in 41 (12 %), and T3 withdrawal in 94 (28 %) measurements. The overall mean +/- 1SD for Stim-Tg and u-hsTg measured was 1.0 +/- 1.2 and 0.2 +/- 0.1 MUg/L, respectively. When adjusted for method of TSH stimulation, serial Stim-Tg measurements did not significantly change over time (all p = NS). The estimated changes in Stim-Tg per year for rhTSH, T4 withdrawal, and T3 withdrawal were 0.01, -0.08, and 0.04 MUg/L, respectively. Upon exclusion of 73 patients with an initial undetectable Stim-Tg (n = 48), serial Stim-Tg measurements did not change significantly over time (all p = NS). For these patients, the estimated changes in Stim-Tg per year for rhTSH, T4 withdrawal, and T3 withdrawal were -0.09, -0.10, and 0.01 MUg/L, respectively. Serial u-hsTg measurements did not significantly change over time after adjusting for TSH level (p = NS). The estimated change in u-hsTg per year was -0.003 MUg/L. No patients had any clinical or imaging evidence of a recurrence during the duration of their follow-up. Among low/intermediate-risk PTC patients not treated with RAI, serial post-surgical Stim-Tg and u-hsTg measurements do not change significantly over a median follow-up of 6.5 years. PMID- 27189149 TI - Technical Assessment of Connector-Assisted Nerve Repair. AB - PURPOSE: Clinical outcomes of nerve repair have not substantially improved over the last several decades. Although clearly a multifactorial problem, basic principles including proper fascicular alignment are not always realized. The use of short conduits as connectors may enhance nerve alignment by entubulating and directing the approximation of nerve ends. METHODS: Ten hand surgeons (5 experienced and 5 inexperienced) performed a series of in vitro human cadaver nerve repairs. Three small-diameter (2 mm), 3 medium-diameter (3-4 mm), and 3 large-diameter (5-6 mm) nerves were repaired (under 10* magnification) utilizing each of 3 techniques: suture-only, connector-only (sutures placed through the ends of the connector), and connector-assisted (alignment sutures at the nerve interface plus connector). Three judges (blinded to who performed the repairs) assessed each repair for fascicular alignment based on predetermined qualitative scales. RESULTS: Across all surgeons, 23 of 30 connector-assisted repairs were judged good or excellent versus 18 of 30 of the suture-only and 13 of 30 of the connector-only repairs. Experienced surgeons in general did better repairs and in particular were more likely to obtain superior alignment for conduit-only repairs (73.3% vs 13.3% good or excellent) and suture-only repairs (73.3% vs 46.7% good or excellent) and were not statistically different for connector-assisted repairs (86.7% vs 66.7% good or excellent) compared with inexperienced surgeons. CONCLUSIONS: In a cadaver nerve model, there was no significant difference in the technical alignment of conduit-assisted repairs between experienced and inexperienced surgeons whereas inexperienced surgeons were more likely to achieve inadequate alignment with suture-only or conduit-only repairs. CLINICAL RELEVANCE: Connector-assisted repairs combining suture-approximation and entubulation may improve the technical alignment of nerve repairs performed, especially by less-experienced surgeons. PMID- 27189151 TI - Letter Regarding "A Simpler Solution to Distal Digital Replantation". PMID- 27189150 TI - Using Hounsfield Units to Assess Osteoporotic Status on Wrist Computed Tomography Scans: Comparison With Dual Energy X-Ray Absorptiometry. AB - PURPOSE: Rates of evaluation and treatment for osteoporosis following distal radius fragility fractures remain low. As a subset of patients with these fractures undergo diagnostic computed tomography (CT) scan of the wrist, utilizing bone mineral density (BMD) measurements available with this imaging can be used to detect osteopenia or osteoporosis. This information may consequently prompt intervention to prevent a subsequent fracture. The purpose of this study was to determine if Hounsfield unit (HU) measurements at the wrist correlate with BMD measurements of the hip, femoral neck, and lumbar spine and to assess the ability of these HU measurements to detect osteoporosis of the hip. METHODS: Forty-five female patients with distal radius fractures who underwent CT scan and dual energy x-ray absorptiometry scan as part of the management of their wrist fracture were identified. Bone mineral density measurements were made using the regional cancellous bone HU value at the capitate and compared with values obtained by a dual energy x-ray absorptiometry scan. RESULTS: Hounsfield unit values at the capitate were significantly correlated with BMD and t scores at the femoral neck, hip, and lumbar spine. An HU threshold of 307 in the capitate optimized sensitivity (86%) and specificity (94%) for detecting osteoporotic patients. CONCLUSIONS: By demonstrating that capitate HU measurements from clinical CT scans are correlated with BMD and t scores at the hip, femoral neck, and lumbar spine, our data suggest that clinical CT scans should have a role in detecting osteopenia and osteoporosis. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic III. PMID- 27189152 TI - Adding Injury to Insult: A National Analysis of Combat Sport-Related Facial Injury. AB - OBJECTIVES/HYPOTHESIS: To estimate the incidence of patients presenting to emergency departments (EDs) for facial trauma sustained from participation in combat sports and evaluate injury patterns and patient demographics. METHODS: The National Electronic Injury Surveillance System (NEISS) was evaluated for facial injuries from wrestling, boxing, and martial arts leading to ED visits from 2008 to 2013. Relevant entries were examined for injury mechanism, location, type, as well as other patient characteristics. RESULTS: There were 1143 entries extrapolating to an estimated 42 395 ED visits from 2008 to 2013. Injury rates for boxing, marital arts, and wrestling were, respectively, 44, 56, and 120 injuries per 100 000 participants. Males comprised the majority (93.7%). A plurality of injuries involved lacerations (46.0%), followed by fractures (26.2%) and contusions/abrasions (19.3%). The proportion of fractures was highest among boxers (36.9%). Overall, the most common mechanisms of injury were punching, kicking, and head butting. CONCLUSIONS: The significant number of ED visits resulted from combat sports facial trauma, reinforcing the importance of familiarity with injury patterns among practitioners managing facial trauma. As most injuries involve individuals younger than 19 despite guidelines suggesting children and adolescents avoid combat sports, these findings may be used for patient education and encouragement of the use of personal protective equipment. Furthermore, injury patterns reported in this analysis may serve as an adjunct for enhancing clinical history taking and physical examination. PMID- 27189153 TI - What Happens With Untreated Nasal Polyps Over Time? A 13-Year Prospective Study. AB - OBJECTIVES: Nasal polyps are often seen in ENT practice, but little is known about the pathogenesis and the natural development. Our objective was to follow individuals with untreated nasal polyps prospectively, in terms of polyp size, symptoms, and respiratory function. METHODS: Thirty-three individuals, aged 27 to 87 years, with untreated nasal polyps were identified in a population-based study. Peak nasal inspiratory flow, olfactory function, and size of the nasal polyps were examined. Respiratory symptoms were also registered. Follow-up examinations were performed after 6 and 13 years, with change between visits analyzed. RESULTS: Over time, polyp size as well as occurrence of unilateral or bilateral polyps varied without an obvious pattern, with no consistent trends in respiratory function or symptoms. Twenty-one individuals (64%) were still untreated at the 6-year follow-up, and 12 (36%) remained untreated during the whole 13-year follow-up. Dropouts were due mainly to death. Seven individuals (21%) started treatment during the follow-up and had larger polyps and more subjective respiratory symptoms at baseline compared to the untreated group. CONCLUSION: Nasal polyps found occasionally are often part of a chronic entity but do not necessarily evolve into a more serious condition over time. Treatment should therefore be based on the patients' subjective problems. PMID- 27189155 TI - The role of insulin pump therapy for type 2 diabetes mellitus. AB - Many patients with type 2 diabetes fail to achieve adequate glucose control despite escalation of treatment and combinations of multiple therapies including insulin. Patients with long-standing type 2 diabetes often suffer from the combination of severe insulin deficiency in addition to insulin resistance, thereby requiring high doses of insulin delivered in multiple injections to attain adequate glycemic control. Insulin-pump therapy was first introduced in the 1970s as an approach to mimic physiological insulin delivery and attain normal glucose in patients with type 1 diabetes. The recent years have seen an increase in the use of this technology for patients with type 2 diabetes. This article summarizes the clinical studies evaluating insulin pump use in patients with type 2 diabetes and discusses the benefits and shortcomings of pump therapy in this population. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27189154 TI - Access to Health Care and Hearing Evaluation in US Adults. AB - OBJECTIVES: To explore self-reported hearing testing access for adults in a nationally representative survey. METHODS: Demographic and audiologic adult survey respondent variables in the National Health and Nutrition Examination Survey (NHANES) database 2011-2012 cohort were examined. Logistic regression was used to determine odds ratios (OR) and 95% confidence intervals (CI). RESULTS: In all, 5864 adult respondents were analyzed. Two-thirds (65.6%) of respondents reported having hearing tested 10 or more years ago or never tested at all. Male gender (OR = 2.27; 95% CI, 1.31-3.94), having a health care visit less than 3 years ago (OR = 8.19; 95% CI, 2.09-32.2), and having health insurance (OR = 1.73; 95% CI, 1.08-2.77) were significantly associated with respondents reporting having a hearing test less than 10 years ago. Mexican American race (OR = 0.41; 95% CI, 0.20-0.83) and respondent age 40 to 59 (OR = 0.52; 95% CI, 0.33-0.81) were significantly associated with respondents reporting having a hearing test 10 or more years prior or never. CONCLUSION: A significant proportion of the adult population reports having hearing tested 10 or more years prior or never at all. Effort will be required to identify adults who have hearing loss and may benefit from auditory rehabilitation such as hearing aids or the cochlear implant. PMID- 27189156 TI - Cryoballoon ablation for pulmonary vein isolation in patients with atrial fibrillation: preliminary results using novel short-tip cryoballoon. AB - PURPOSE: In this study, we aimed to report our preliminary experience regarding the impact of the novel short-tip (ST) cryoballoon (CB) on procedural efficacy and signal quality during pulmonary vein (PV) isolation for both paroxysmal and persistent atrial fibrillation. METHODS: Between March, 2015, and August, 2015, we enrolled a total of 64 patients (47 patients male, 73 %) with a mean age of 60 +/- 11 years. In the study population, 31 patients (48 %) underwent PVI using Advance (ADV) CB and 33 (52 %) patients with ST CB. In all patients, a 28-mm balloon was used. RESULTS: Acute procedural success rates were 100 % for the entire study population. A statistically insignificant increase in the percentage of PV signal recordings was observed with ST CB in all PVs compared to ADV CB [88 vs. 81 % for left superior PV (LSPV), 82 vs. 78 % for left inferior PV (LIPV), 85 vs. 84 % for right superior PV (RSPV), 82 vs. 71 % for right inferior PV (RIPV), p < 0.05]. Additionally, the difference in minimum temperature reached during the procedure per PV was not statistically significant between ST CB and ADV CB except the LIPV (LSPV -44.2 +/- 5.9 vs. -45.6 +/- 5.3 degrees C, p = 0.970; LIPV -38.7 +/- 4.6 degrees C vs -44.6 +/- 6.8 degrees C, p < 0.001; RSPV -45.6 +/- 7.4 degrees C vs.-47.2 +/- 6.1 degrees C, p = 0.168; RIPV -41.4 +/- 5.1 degrees C vs.-43.7 +/- 6.3 degrees C, p = 0.360). Time to isolation for each PV was similar between ST and ADV CB (p > 0.05). CONCLUSION: Our preliminary findings indicated similar acute procedural success for the novel ST CB compared with second generation ADV CB. The increase in the ratio of PV signal recordings obtained during the PVI using the novel ST CB was not significant. PMID- 27189157 TI - Steerable versus non-steerable sheaths during pulmonary vein isolation: impact of left atrial enlargement on the catheter-tissue contact force. AB - PURPOSE: The influence of left atrial (LA) enlargement on the efficacy of steerable sheath usage during pulmonary vein (PV) isolation is poorly understood. Here, we compared the catheter-tissue contact force (CF) and clinical outcomes between steerable and non-steerable sheaths among patients with different severities of LA enlargement. METHODS: In this prospective observational study, 90 consecutive atrial fibrillation patients scheduled for PV isolation (paroxysmal, 67 %) were enrolled and divided into tertiles of the LA volume (LA1, <124 cm3; LA2, 124 to 145 cm3; LA3, >=146 cm3). An ipsilateral PV isolation was completed using either a steerable (n = 57) or non-steerable sheath (n = 33). RESULTS: The average CF of each ipsilateral PV was lower in the LA3 group (right 13.8 +/- 5.8 g; left 9.7 +/- 5.2 g) than LA1 (right 15.6 +/- 6.8 g, p = 0.005; left 12.5 +/- 5.6 g, p < 0.0001) or LA2 (right 15.2 +/- 7.3 g, p = 0.04; left 12.6 +/- 5.3 g, p < 0.0001) groups. In total, the average CF around the left PVs was significantly higher with steerable sheaths than without (12.7 +/- 5.5 vs. 10.2 +/- 4.9 g, p = 0.03). Subgroup analysis revealed that a tendency toward higher CF around the left PVs was observed in the LA3 group (12.3 +/- 7.3 vs. 8.5 +/- 3.9 g, p = 0.08) but was not in the LA1 and LA2 groups. Further, in the LA3 group, steerable sheath usage showed better clinical outcomes: shorter procedural (55 +/- 29 min vs. 81 +/- 39 min, p = 0.04) and fluoroscopic times (27 +/- 11 min vs. 37 +/- 17 min, p = 0.045) and a tendency toward a lower 1-year AF recurrence rate (39 vs. 12 %, p = 0.09). CONCLUSIONS: The beneficial effects of using steerable sheaths were more prominent in patients with severe LA enlargement. PMID- 27189158 TI - Pseudoruegeria aestuarii sp. nov., of the family Rhodobacteraceae, isolated from a tidal flat. AB - A Gram-stain-negative, non-motile, aerobic and rod-shaped bacterium, designated strain MME-001T, was isolated from the tidal flat of Muui-do in the Republic of Korea. Phylogenetic trees based on the 16S rRNA gene sequence showed that strain MME-001T belonged to the genus Pseudoruegeria in the family Rhodobacteraceae and that it shared the highest 16S rRNA gene sequence similarity with Pseudoruegeria sabulilitoris GJMS-35T (98.0 % similarity of the 16S rRNA gene). Growth of strain MME-001T occurred in the presence of 1.0-7.0 % (w/v) NaCl at 15-40 degrees C and pH 7.0-9.0, with optimal growth in the presence of 2.0-3.0 % (w/v) NaCl at 25-30 degrees C and pH 7.0. Ubiquinone-10 was the major respiratory quinone. Major polar lipids were phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol and an unidentified lipid. The major cellular fatty acids were C18 : 1omega7c and C16 : 0. The genomic DNA G+C content was 62 mol%. DNA-DNA hybridization values between strain MME-001T and P. sabulilitoris KCTC 42111T, 'Pseudoruegeria limi' KCTC 32460, Pseudoruegeria lutimaris KCTC 22690T, Pseudoruegeria aquimaris KCTC 12737T and Pseudoruegeriahaliotis KACC 17214T was 36+/-5, 57+/-7, 34+/-4, 18+/-5 and 21+/-3 %, respectively. Based on the phenotypic and phylogenetic taxonomical properties, this strain MME-001T represents a novel species of the genus Pseudoruegeria, for which the name Pseudoruegeria aestuarii sp. nov. is proposed. The type strain is MME-001T (=KCCM 43133T=JCM 30751T). PMID- 27189159 TI - Lower functional connectivity of default mode network in cognitively normal young adults with mutation of APP, presenilins and APOE epsilon4. AB - In this study, we used resting-state functional magnetic resonance imaging to explore the genetic effects of amyloid precursor protein (APP) or presenilins mutation and apolipoprotein E (APOE) epsilon4 on the default-mode network (DMN) in cognitively intact young adults (24.1 +/- 2.5 years). Both the APP or presenilin-1/2 group and the APOE epsilon4 group had significantly lower DMN functional connectivity (FC) in the some brain regions like precuneus/middle cingulate cortices (PCu/MCC) than controls (AlphaSim corrected, P < 0.05). Only a lower FC tendency was demonstrated (control < APOE epsilon4 < APP or presenilin 1/2 group). Moreover, lower FC in PCu/MCC is correlated with some neuropsychological assessments such as similarity test in APOE epsilon4 group. These findings indicate that DMN FC alteration in APP or presenilin-1/2 or APOE epsilon4 subjects is prior to the occurrence of neurological alterations and clinical symptoms, and DMN FC might be a valuable biomarker to detect genetic risk in the preclinical stage. PMID- 27189161 TI - RNA-Seq following PCR-based sorting reveals rare cell transcriptional signatures. AB - BACKGROUND: Rare cell subtypes can profoundly impact the course of human health and disease, yet their presence within a sample is often missed with bulk molecular analysis. Single-cell analysis tools such as FACS, FISH-FC and single cell barcode-based sequencing can investigate cellular heterogeneity; however, they have significant limitations that impede their ability to identify and transcriptionally characterize many rare cell subpopulations. RESULTS: PCR activated cell sorting (PACS) is a novel cytometry method that uses single-cell TaqMan PCR reactions performed in microfluidic droplets to identify and isolate cell subtypes with high-throughput. Here, we extend this method and demonstrate that PACS enables high-dimensional molecular profiling on TaqMan-targeted cells. Using a random priming RNA-Seq strategy, we obtained high-fidelity transcriptome measurements following PACS sorting of prostate cancer cells from a heterogeneous population. The sequencing data revealed prostate cancer gene expression profiles that were obscured in the unsorted populations. Single-cell expression analysis with PACS was subsequently used to confirm a number of the differentially expressed genes identified with RNA sequencing. CONCLUSIONS: PACS requires minimal sample processing, uses readily available TaqMan assays and can isolate cell subtypes with high sensitivity. We have now validated a method for performing next-generation sequencing on mRNA obtained from PACS isolated cells. This capability makes PACS well suited for transcriptional profiling of rare cells from complex populations to obtain maximal biological insight into cell states and behaviors. PMID- 27189160 TI - Diagnostic, prognostic and predictive value of cell-free miRNAs in prostate cancer: a systematic review. AB - Prostate cancer, the second most frequently diagnosed cancer in males worldwide, is estimated to be diagnosed in 1.1 million men per year. Introduction of PSA testing substantially improved early detection of prostate cancer, however it also led to overdiagnosis and subsequent overtreatment of patients with an indolent disease. Treatment outcome and management of prostate cancer could be improved by the development of non-invasive biomarker assays that aid in increasing the sensitivity and specificity of prostate cancer screening, help to distinguish aggressive from indolent disease and guide therapeutic decisions. Prostate cancer cells release miRNAs into the bloodstream, where they exist incorporated into ribonucleoprotein complexes or extracellular vesicles. Later, cell-free miRNAs have been found in various other biofluids. The initial RNA sequencing studies suggested that most of the circulating cell-free miRNAs in healthy individuals are derived from blood cells, while specific disease associated miRNA signatures may appear in the circulation of patients affected with various diseases, including cancer. This raised a hope that cell-free miRNAs may serve as non-invasive biomarkers for prostate cancer. Indeed, a number of cell-free miRNAs that potentially may serve as diagnostic, prognostic or predictive biomarkers have been discovered in blood or other biofluids of prostate cancer patients and need to be validated in appropriately designed longitudinal studies and clinical trials. In this review, we systematically summarise studies investigating cell-free miRNAs in biofluids of prostate cancer patients and discuss the utility of the identified biomarkers in various clinical scenarios. Furthermore, we discuss the possible mechanisms of miRNA release into biofluids and outline the biological questions and technical challenges that have arisen from these studies. PMID- 27189162 TI - Tumor-Infiltrating Lymphocytes: A Predictive and Prognostic Biomarker in Neoadjuvant-Treated HER2-Positive Breast Cancer. AB - PURPOSE: We elucidated the value of tumor-infiltrating lymphocytes (TIL) as an independent predictor for pathologic complete response (pCR) rate and as a prognostic marker for disease-free survival (DFS) in patients with HER2-positive breast cancer in the neoadjuvant setting. EXPERIMENTAL DESIGN: We evaluated stromal TILs in 498 HER2-positive breast cancer samples of the neoadjuvant GeparQuattro (G4) and GeparQuinto (G5) trials. Levels of TILs were determined as a continuous parameter per 10% increase and as lymphocyte-predominant breast cancer (LPBC; >= 60% TILs), and correlated with pCR rate and DFS. RESULTS: In the complete cohort, HER2-positive LPBC cases had a significantly increased pCR rates compared with non-LPBC types. They were significant predictors for pCR in univariate (10% TILs: OR 1.12, P = 0.002; LPBC: OR 2.02, P = 0.002) and multivariate analyses (10% TILs: OR 1.1, P = 0.014; LPBC: OR 1.87, P = 0.009). This effect was also detectable in the trastuzumab-treated (10% TILs: OR 1.12, P = 0.018; LPBC: OR 2.08, P = 0.013) but not in the lapatinib-treated subgroup. We identified a low-risk (pCR/LPBC) and a high-risk group (no pCR/no LPBC) regarding DFS. In triple-positive breast cancer, TILs are of more prognostic relevance than pCR. CONCLUSIONS: We could demonstrate the predictive and prognostic impact of TILs in HER2-positive breast cancer in the neoadjuvant setting. In combination with pCR rate, TILs may help to stratify prognostic subgroups, thereby guiding future therapy decisions. Clin Cancer Res; 22(23); 5747-54. (c)2016 AACR. PMID- 27189163 TI - The Effect of Hepatic Impairment on Outcomes in Phase I Clinical Trials in Cancer Subjects. AB - PURPOSE: The NCI Cancer Therapy Evaluation Program sponsors hepatic dysfunction phase I clinical trials (HDCT) and phase 1 clinical trials (P1CT) to determine safe doses and schedules of antineoplastic therapeutics. We sought to compare clinical outcomes between these trial types while stratifying by hepatotoxic agents. EXPERIMENTAL DESIGN: Individual subject data were extracted from the records of 51 NCI-sponsored HDCT and P1CT. The NCI's Organ Dysfunction Working Group's hepatic impairment categorization and two drug-induced liver injury (DILI) scales (FDA R ratio and Hy's law) were used to classify subjects. The number of cycles administered and treatment discontinuation reason were also evaluated and compared between groups. RESULTS: There were 513 and 1,328 subjects treated on HDCT (n = 9) and P1CT (n = 42), respectively. There were differing patterns of DILI with significant worsening of total bilirubin in subjects on HDCT, and worsening of alanine aminotransferase (ALT) in subjects on P1CT. Cholestatic peak patterns of liver impairment (predominant increases in alkaline phosphatase rather than transaminases) were more frequent in HDCT. Criteria for Hy's law were met by 11 subjects on P1CT, but not by any subjects on HDCT. Disease progression was the most common reason for treatment discontinuation, followed by adverse events at similar frequencies in both HDCT and P1CT. CONCLUSIONS: The differential effects on hepatotoxicity suggest that underlying hepatic function may affect susceptibility to and patterns of DILI. The incorporation of additional measures of hepatic function may help identify those at highest risk of hepatotoxicity in future trials because baseline liver tests did not. Clin Cancer Res; 22(22); 5472-9. (c)2016 AACR. PMID- 27189164 TI - Biased Expression of the FOXP3Delta3 Isoform in Aggressive Bladder Cancer Mediates Differentiation and Cisplatin Chemotherapy Resistance. AB - PURPOSE: The transcriptional regulation mediating cancer cell differentiation into distinct molecular subtypes and modulating sensitivity to existing treatments is an enticing therapeutic target. Our objective was to characterize the ability of the forkhead/winged transcription factor FOXP3 to modulate the differentiation of bladder cancer. EXPERIMENTAL DESIGN: Expression of FOXP3 was analyzed by immunohistochemistry in a tumor microarray of 587 samples and overall survival in a subset of 187 patients following radical cystectomy. Functional assays were performed in SW780 and HT1376 cell lines in vitro and in vivo and gene expression profiling performed by RNA-Seq. Validation was undertaken using gene expression profiles of 131 patients from The Cancer Genome Atlas (TCGA) consortium in bladder cancer. RESULTS: FOXP3 expression correlates with bladder cancer stage and inversely with overall survival, with biased expression of the FOXP3Delta3 isoform. Functional assays of FOXP3Delta3 demonstrated resistance to chemotherapy in vitro, whereas subcutaneous xenografts overexpressing FOXP3Delta3 developed larger and more poorly differentiated bladder cancers. RNA expression profiling revealed a unique FOXP3Delta3 gene signature supporting a role in chemotherapy resistance. Accordingly, knockdown of Foxp3 by siRNA in HT1376 cells conferred sensitivity to cisplatin- and gemcitabine-induced cytotoxicity. Validation in TCGA dataset demonstrated increased expression of FOXP3 in subtypes II to IV and skewing of molecular subtypes based on FOXP3Delta3-specific gene expression. CONCLUSIONS: (i) Biased expression of the FOXP3Delta3 isoform in bladder cancer inversely correlates with overall survival, (ii) FOXP3Delta3 induces a unique gene program that mediates cancer differentiation, and (iii) FOXP3Delta3 may augment chemotherapy resistance. Clin Cancer Res; 22(21); 5349 61. (c)2016 AACR. PMID- 27189165 TI - Characterization of CD33/CD3 Tetravalent Bispecific Tandem Diabodies (TandAbs) for the Treatment of Acute Myeloid Leukemia. AB - PURPOSE: Randomized studies with gemtuzumab ozogamicin have validated CD33 as a target for antigen-specific immunotherapy of acute myelogenous leukemia (AML). Here, we investigated the potential of CD33/CD3-directed tandem diabodies (TandAbs) as novel treatment approach for AML. These tetravalent bispecific antibodies provide two binding sites for each antigen to maintain the avidity of a bivalent antibody and have a molecular weight exceeding the renal clearance threshold, thus offering a longer half-life compared to smaller antibody constructs. EXPERIMENTAL DESIGN: We constructed a series of TandAbs composed of anti-CD33 and anti-CD3 variable domains of diverse binding affinities and profiled their functional properties in CD33+ human leukemia cell lines, xenograft models, and AML patient samples. RESULTS: Our studies demonstrated that several CD33/CD3 TandAbs could induce potent, dose-dependent cytolysis of CD33+ AML cell lines. This effect was modulated by the effector-to-target cell ratio and strictly required the presence of T cells. Activation and proliferation of T cells and maximal AML cell cytolysis correlated with high avidity to both CD33 and CD3. High-avidity TandAbs were broadly active in primary specimens from patients with newly diagnosed or relapsed/refractory AML in vitro, with cytotoxic properties independent of CD33 receptor density and cytogenetic risk. Tumor growth delay and inhibition were observed in both prophylactic and established HL 60 xenograft models in immunodeficient mice. CONCLUSIONS: Our data show high efficacy of CD33/CD3 TandAbs in various preclinical models of human AML. Together, these findings support further study of CD33/CD3 TandAbs as novel immunotherapeutics for patients with AML. Clin Cancer Res; 22(23); 5829-38. (c)2016 AACR. PMID- 27189167 TI - Safe engineering of CAR T cells for adoptive cell therapy of cancer using long term episomal gene transfer. AB - Chimeric antigen receptor (CAR) T-cell therapy is a new successful treatment for refractory B-cell leukemia. Successful therapeutic outcome depends on long-term expression of CAR transgene in T cells, which is achieved by delivering transgene using integrating gamma retrovirus (RV) or lentivirus (LV). However, uncontrolled RV/LV integration in host cell genomes has the potential risk of causing insertional mutagenesis. Herein, we describe a novel episomal long-term cell engineering method using non-integrating lentiviral (NILV) vector containing a scaffold/matrix attachment region (S/MAR) element, for either expression of transgenes or silencing of target genes. The insertional events of this vector into the genome of host cells are below detection level. CD19 CAR T cells engineered with a NILV-S/MAR vector have similar levels of CAR expression as T cells engineered with an integrating LV vector, even after numerous rounds of cell division. NILV-S/MAR-engineered CD19 CAR T cells exhibited similar cytotoxic capacity upon CD19(+) target cell recognition as LV-engineered T cells and are as effective in controlling tumor growth in vivo We propose that NILV-S/MAR vectors are superior to current options as they enable long-term transgene expression without the risk of insertional mutagenesis and genotoxicity. PMID- 27189166 TI - Circulating Neutrophil Extracellular Trap Levels in Well-Controlled Type 2 Diabetes and Pathway Involved in Their Formation Induced by High-Dose Glucose. AB - OBJECTIVES: Although intensive therapy for type 2 diabetes (T2D) prevents microvascular complications, 10% of well-controlled T2D patients develop microangiopathy. Therefore, the identification of risk markers for microvascular complications in well-controlled T2D patients is important. Recent studies have demonstrated that high-dose glucose induces neutrophil extracellular trap (NET) formation, which can be a risk for microvascular disorders. Thus, we attempted to determine the correlation of circulating NET levels with clinical/laboratory parameters in well-controlled T2D patients and to reveal the mechanism of NET formation induced by high-dose glucose. METHODS: Circulating NET levels represented by myeloperoxidase (MPO)-DNA complexes in the serum of 11 well controlled T2D patients and 13 healthy volunteers were determined by enzyme linked immunosorbent assay. The pathway involved in the NET formation induced by high-dose glucose was determined using specific inhibitors. RESULTS: Serum MPO DNA complex levels were significantly higher in some well-controlled T2D patients in correlation with the clinical/laboratory parameters which have been regarded as risk markers for microvascular complications. The aldose reductase inhibitor, ranirestat, could inhibit the NET formation induced by high-dose glucose. CONCLUSIONS: Elevated levels of circulating NETs can be a risk marker for microvascular complications in well-controlled T2D patients. The polyol pathway is involved in the NET formation induced by high-dose glucose. PMID- 27189168 TI - The impact of genome-wide association studies on the pathophysiology and therapy of cardiovascular disease. AB - Cardiovascular diseases are leading causes for death worldwide. Genetic disposition jointly with traditional risk factors precipitates their manifestation. Whereas the implications of a positive family history for individual risk have been known for a long time, only in the past few years have genome-wide association studies (GWAS) shed light on the underlying genetic variations. Here, we review these studies designed to increase our understanding of the pathophysiology of cardiovascular diseases, particularly coronary artery disease and myocardial infarction. We focus on the newly established pathways to exemplify the translation from the identification of risk-related genetic variants to new preventive and therapeutic strategies for cardiovascular disease. PMID- 27189170 TI - Brain endothelial cell-targeted gene therapy of neurovascular disorders. PMID- 27189169 TI - Smooth muscle FGF/TGFbeta cross talk regulates atherosclerosis progression. AB - The conversion of vascular smooth muscle cells (SMCs) from contractile to proliferative phenotype is thought to play an important role in atherosclerosis. However, the contribution of this process to plaque growth has never been fully defined. In this study, we show that activation of SMC TGFbeta signaling, achieved by suppression of SMC fibroblast growth factor (FGF) signaling input, induces their conversion to a contractile phenotype and dramatically reduces atherosclerotic plaque size. The FGF/TGFbeta signaling cross talk was observed in vitro and in vivo In vitro, inhibition of FGF signaling increased TGFbeta activity, thereby promoting smooth muscle differentiation and decreasing proliferation. In vivo, smooth muscle-specific knockout of an FGF receptor adaptor Frs2alpha led to a profound inhibition of atherosclerotic plaque growth when these animals were crossed on Apoe(-/-) background and subjected to a high fat diet. In particular, there was a significant reduction in plaque cellularity, increase in fibrous cap area, and decrease in necrotic core size. In agreement with these findings, examination of human coronary arteries with various degrees of atherosclerosis revealed a strong correlation between the activation of FGF signaling, loss of TGFbeta activity, and increased disease severity. These results identify SMC FGF/TGFbeta signaling cross talk as an important regulator of SMC phenotype switch and document a major contribution of medial SMC proliferation to atherosclerotic plaque growth. PMID- 27189171 TI - Molecular probes for cardiovascular imaging. AB - Molecular probes provide imaging signal and contrast for the visualization, characterization, and measurement of biological processes at the molecular level. These probes can be designed to target the cell or tissue of interest and must be retained at the imaging site until they can be detected by the appropriate imaging modality. In this article, we will discuss the basic design of molecular probes, differences among the various types of probes, and general strategies for their evaluation of cardiovascular disease. PMID- 27189172 TI - Myocardial perfusion with single-photon emission computed tomography, multidetector computed tomography, or neither? PMID- 27189174 TI - Study design for non-recurring, time-to-event outcomes in the presence of error prone diagnostic tests or self-reports. AB - Sequentially administered, laboratory-based diagnostic tests or self-reported questionnaires are often used to determine the occurrence of a silent event. In this paper, we consider issues relevant in design of studies aimed at estimating the association of one or more covariates with a non-recurring, time-to-event outcome that is observed using a repeatedly administered, error-prone diagnostic procedure. The problem is motivated by the Women's Health Initiative, in which diabetes incidence among the approximately 160,000 women is obtained from annually collected self-reported data. For settings of imperfect diagnostic tests or self-reports with known sensitivity and specificity, we evaluate the effects of various factors on resulting power and sample size calculations and compare the relative efficiency of different study designs. The methods illustrated in this paper are readily implemented using our freely available R software package icensmis, which is available at the Comprehensive R Archive Network website. An important special case is that when diagnostic procedures are perfect, they result in interval-censored, time-to-event outcomes. The proposed methods are applicable for the design of studies in which a time-to-event outcome is interval censored. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27189173 TI - Novel strong promoter of antimicrobial peptides gene pro-SmAMP2 from chickweed (Stellaria media). AB - BACKGROUND: In a previous study we found that in chickweed the expression level of the pro-SmAMP2 gene was comparable or even higher to that of the beta-actin gene. This high level of the gene expression has attracted our attention as an opportunity for the identification of novel strong promoters of plant origin, which could find its application in plant biotechnology. Therefore, in the present study we focused on the nucleotide sequence identification and the functional characteristics of the pro-SmAMP2 promoter in transgenic plants. RESULTS: In chickweed (Stellaria media), a 2120 bp promoter region of the pro SmAMP2 gene encoding antifungal peptides was sequenced. Six 5'-deletion variants 2120, -1504, -1149, -822, -455, and -290 bp of pro-SmAMP2 gene promoter were fused with the coding region of the reporter gene gusA in the plant expression vector pCambia1381Z. Independent transgenic plants of tobacco Nicotiana tabacum were obtained with each genetic structure. GUS protein activity assay in extracts from transgenic plants showed that all deletion variants of the promoter, except 290 bp, expressed the gusA gene. In most transgenic plants, the GUS activity level was comparable or higher than in plants with the viral promoter CaMV 35S. GUS activity remains high in progenies and its level correlates positively with the amount of gusA gene mRNA in T3 homozygous plants. The activity of the rro SmAMP2 promoter was detected in all organs of the transgenic plants studied, during meiosis and in pollen as well. CONCLUSION: Our results show that the rro SmAMP2 promoter can be used for target genes expression control in transgenic plants. PMID- 27189176 TI - Five minutes with . . . David Field, coauthor of perinatal mortality report. PMID- 27189177 TI - IgA nephropathy. AB - Globally, IgA nephropathy (IgAN) is the most common primary glomerulonephritis that can progress to renal failure. The exact pathogenesis of IgAN is not well defined, but current biochemical and genetic data implicate overproduction of aberrantly glycosylated IgA1. These aberrant immunoglobulins are characterized by galactose deficiency of some hinge-region O-linked glycans. However, aberrant glycosylation alone is insufficient to induce renal injury: the participation of glycan-specific IgA and IgG autoantibodies that recognize the undergalactosylated IgA1 molecule is required. Glomerular deposits of immune complexes containing undergalactosylated IgA1 activate mesangial cells, leading to the local overproduction of cytokines, chemokines and complement. Emerging data indicate that mesangial-derived mediators that are released following mesangial deposition of IgA1 lead to podocyte and tubulointerstitial injury via humoral crosstalk. Patients can present with a range of signs and symptoms, from asymptomatic microscopic haematuria to macroscopic haematuria. The clinical progression varies, with 30-40% of patients reaching end-stage renal disease 20-30 years after the first clinical presentation. Currently, no IgAN-specific therapies are available and patients are managed with the aim of controlling blood pressure and maintaining renal function. However, new therapeutic approaches are being developed, building upon our ever-improving understanding of disease pathogenesis. PMID- 27189175 TI - Mitochondrial dysfunction in inflammatory responses and cellular senescence: pathogenesis and pharmacological targets for chronic lung diseases. AB - Mitochondria are dynamic organelles, which couple the various cellular processes that regulate metabolism, cell proliferation and survival. Environmental stress can cause mitochondrial dysfunction and dynamic changes including reduced mitochondrial biogenesis, oxidative phosphorylation and ATP production, as well as mitophagy impairment, which leads to increased ROS, inflammatory responses and cellular senescence. Oxidative stress, inflammation and cellular senescence all have important roles in the pathogenesis of chronic lung diseases, such as chronic obstructive pulmonary disease, pulmonary fibrosis and bronchopulmonary dysplasia. In this review, we discuss the current state on how mitochondrial dysfunction affects inflammatory responses and cellular senescence, the mechanisms of mitochondrial dysfunction underlying the pathogenesis of chronic lung diseases and the potential of mitochondrial transfer and replacement as treatments for these diseases. PMID- 27189178 TI - Two HAP2-GCS1 homologs responsible for gamete interactions in the cellular slime mold with multiple mating types: Implication for common mechanisms of sexual reproduction shared by plants and protozoa and for male-female differentiation. AB - Fertilization is a central event in sexual reproduction, and understanding its molecular mechanisms has both basic and applicative biological importance. Recent studies have uncovered the molecules that mediate this process in a variety of organisms, making it intriguing to consider conservation and evolution of the mechanisms of sexual reproduction across phyla. The social amoeba Dictyostelium discoideum undergoes sexual maturation and forms gametes under dark and humid conditions. It exhibits three mating types, type-I, -II, and -III, for the heterothallic mating system. Based on proteome analyses of the gamete membranes, we detected expression of two homologs of the plant fertilization protein HAP2 GCS1. When their coding genes were disrupted in type-I and type-II strains, sexual potency was completely lost, whereas disruption in the type-III strain did not affect mating behavior, suggesting that the latter acts as female in complex organisms. Our results demonstrate the highly conserved function of HAP2-GCS1 in gamete interactions and suggest the presence of additional allo-recognition mechanisms in D. discoideum gametes. PMID- 27189179 TI - Sirt6 cooperates with Blimp1 to positively regulate osteoclast differentiation. AB - Global deletion of the gene encoding a nuclear histone deacetylase sirtuin 6 (Sirt6) in mice leads to osteopenia with a low bone turnover due to impaired bone formation. But whether Sirt6 regulates osteoclast differentiation is less clear. Here we show that Sirt6 functions as a transcriptional regulator to directly repress anti-osteoclastogenic gene expression. Targeted ablation of Sirt6 in hematopoietic cells including osteoclast precursors resulted in increased bone volume caused by a decreased number of osteoclasts. Overexpression of Sirt6 led to an increase in osteoclast formation, and Sirt6-deficient osteoclast precursor cells did not undergo osteoclast differentiation efficiently. Moreover, we showed that Sirt6, induced by RANKL-dependent NFATc1 expression, forms a complex with B lymphocyte-induced maturation protein-1 (Blimp1) to negatively regulate expression of anti-osteoclastogenic gene such as Mafb. These findings identify Sirt6 as a novel regulator of osteoclastogenesis by acting as a transcriptional repressor. PMID- 27189182 TI - Contrasting movement strategies among juvenile albatrosses and petrels. AB - Animal movement is a fundamental eco-evolutionary process yet the behaviour of juvenile animals is largely unknown for many species, especially for soaring seabirds which can range widely over the oceans at low cost. We present an unprecedented dataset of 98 juvenile albatrosses and petrels (nine species), tracked for the first three months after independence. There was a startling diversity within and among species in the type and scale of post-natal movement strategies, ranging from area-restricted to nomadic patterns. Spatial scales were clustered in three groups that ranged from <3000 km to >6000 km from the natal nest. In seven of the nine species, the orientation of flight paths and other movement statistics showed strong similarities between juveniles and adults, providing evidence for innate orientation abilities. Our results have implications for understanding the development of foraging behaviour in naive individuals and the evolution of life history traits such as survival, lifespan and breeding strategy. PMID- 27189181 TI - Percutaneous MR-Guided Cryoablation of Morton's Neuroma: Rationale and Technical Details After the First 20 Patients. AB - OBJECTIVES: The purpose of this study is to discuss technical aspects and rationales of magnetic resonance (MR)-guided cryoablation (CA) of Morton's neuroma (MN); preliminary clinical experience is also retrospectively reviewed. METHODS: Procedures were performed under local anaesthesia on an outpatient basis. Lesion size and location, procedural (technical success, procedural time, complications) and clinical outcomes (patient satisfaction according to a four point scale, residual pain according to a 0-10 visual analogue scale and instances of "stump neuroma") were assessed via chart review and cross-sectional telephone survey after the 20th case. RESULTS: Twenty patients (15 female, 5 male; mean age 50.3 years) were included; 24 MN (mean size 12.7 mm) were treated. Technical success was 100 %. Mean procedural time was 40.9 +/- 10.4 min (range 35 60). One minor complication (superficial cellulitis) was reported (4.2 %). Follow up (mean 19.7 months) was available for 18/24 MN. Patient satisfaction on a per lesion basis was as follows: "completely satisfied" in 77.7 %, "satisfied with minor reservations" in 16.6 % and "satisfied with major reservations" in 5.7 % of cases. Mean pain score at last follow-up post-CA was 3.0. No instances of "stump neuroma" were reported. CONCLUSIONS: MR-guided CA of MN is a novel therapy which appears technically feasible. Clinical advantages of the procedure are high patient satisfaction, reduced risk of "stump neuroma" syndrome and good patient tolerance on an outpatient basis. Further, prospective studies are needed to confirm these encouraging results. PMID- 27189183 TI - Controlling electronic effects and intermolecular packing in contorted polyaromatic hydrocarbons (c-PAHs): towards high mobility field effect transistors. AB - We have investigated the electronic and charge transport properties of two regioisomeric contorted polyaromatic hydrocarbons at the molecular level as well as in the crystalline state. Electron and hole transport is studied on the basis of an incoherent charge hopping model through DFT calculations. For trifluro dibenzoperylene (CF3-DBP, ), which crystallizes as a herringbone network, the computed drift hole and electron mobilities are 0.234 and 0.008 cm(2) V(-1) S( 1), respectively. The greater hole mobility in the DBP crystal (MUh/MUe = 29) can be rationalized by its lower hole reorganization energy and higher hole transfer integral simultaneously. These calculations for the pristine DBP crystal differ from recent experiments indicating its preferential electron conductivity. This might be attributed to the interaction of the molecules with the gold source/drain electrodes. Its second regioisomer, , having a HOMO-LUMO gap of 3.2 eV and thus expectedly inefficient, can be converted into an effective OFET material by replacing the Ph-CF3 groups by oxo groups (>C[double bond, length as m-dash]O) in the 9 and 10 positions (9,10-dioxotribenzopyrene, ). has a suitable HOMO-LUMO gap of 2.18 eV. This bowl-shaped molecule is predicted to pack in a stacked orientation with preferential concaveconcave pairs having a short intermolecular distance of 4.15 A and identical inter-chromophoric electron/hole coupling (th ~ te). This creates an ambipolar charge transport behavior in . Clearly, fine tuning the structure-property relationship opens up the possibility of implanting tailored OFET properties in the existing library of molecules. PMID- 27189184 TI - Internal conversion and intersystem crossing pathways in UV excited, isolated uracils and their implications in prebiotic chemistry. AB - The photodynamic properties of molecules determine their ability to survive in harsh radiation environments. As such, the photostability of heterocyclic aromatic compounds to electromagnetic radiation is expected to have been one of the selection pressures influencing the prebiotic chemistry on early Earth. In the present study, the gas-phase photodynamics of uracil, 5-methyluracil (thymine) and 2-thiouracil-three heterocyclic compounds thought to be present during this era-are assessed in the context of their recently proposed intersystem crossing pathways that compete with internal conversion to the ground state. Specifically, time-resolved photoelectron spectroscopy measurements evidence femtosecond to picosecond timescales for relaxation of the singlet (1)pipi* and (1)npi* states as well as for intersystem crossing to the triplet manifold. Trapping in the excited triplet state and intersystem crossing back to the ground state are investigated as potential factors contributing to the susceptibility of these molecules to ultraviolet photodamage. PMID- 27189180 TI - Effectiveness of a strategy that uses educational games to implement clinical practice guidelines among Spanish residents of family and community medicine (e EDUCAGUIA project): a clinical trial by clusters. AB - BACKGROUND: Clinical practice guidelines (CPGs) have been developed with the aim of helping health professionals, patients, and caregivers make decisions about their health care, using the best available evidence. In many cases, incorporation of these recommendations into clinical practice also implies a need for changes in routine clinical practice. Using educational games as a strategy for implementing recommendations among health professionals has been demonstrated to be effective in some studies; however, evidence is still scarce. The primary objective of this study is to assess the effectiveness of a teaching strategy for the implementation of CPGs using educational games (e-learning EDUCAGUIA) to improve knowledge and skills related to clinical decision-making by residents in family medicine. The primary objective will be evaluated at 1 and 6 months after the intervention. The secondary objectives are to identify barriers and facilitators for the use of guidelines by residents of family medicine and to describe the educational strategies used by Spanish teaching units of family and community medicine to encourage implementation of CPGs. METHODS/DESIGN: We propose a multicenter clinical trial with randomized allocation by clusters of family and community medicine teaching units in Spain. The sample size will be 394 residents (197 in each group), with the teaching units as the randomization unit and the residents comprising the analysis unit. For the intervention, both groups will receive an initial 1-h session on clinical practice guideline use and the usual dissemination strategy by e-mail. The intervention group (e-learning EDUCAGUIA) strategy will consist of educational games with hypothetical clinical scenarios in a virtual environment. The primary outcome will be the score obtained by the residents on evaluation questionnaires for each clinical practice guideline. Other included variables will be the sociodemographic and training variables of the residents and the teaching unit characteristics. The statistical analysis will consist of a descriptive analysis of variables and a baseline comparison of both groups. For the primary outcome analysis, an average score comparison of hypothetical scenario questionnaires between the EDUCAGUIA intervention group and the control group will be performed at 1 and 6 months post intervention, using 95 % confidence intervals. A linear multilevel regression will be used to adjust the model. DISCUSSION: The identification of effective teaching strategies will facilitate the incorporation of available knowledge into clinical practice that could eventually improve patient outcomes. The inclusion of information technologies as teaching tools permits greater learning autonomy and allows deeper instructor participation in the monitoring and supervision of residents. The long-term impact of this strategy is unknown; however, because it is aimed at professionals undergoing training and it addresses prevalent health problems, a small effect can be of great relevance. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02210442 . PMID- 27189186 TI - Can ulipristal acetate be a treatment option for patients with menorrhagia and a history of ischemic cerebrovascular accident? PMID- 27189185 TI - In vitro and in vivo brain-targeting chemo-photothermal therapy using graphene oxide conjugated with transferrin for Gliomas. AB - Current therapies for treating malignant glioma exhibit low therapeutic efficiency because of strong systemic side effects and poor transport across the blood brain barrier (BBB). Herein, we combined targeted chemo-photothermal glioma therapy with a novel multifunctional drug delivery system to overcome these issues. Drug carrier transferrin-conjugated PEGylated nanoscale graphene oxide (TPG) was successfully synthesized and characterized. When loaded on the proposed TPG-based drug delivery (TPGD) system, the anticancer drug doxorubicin could pass through the BBB and improve drug accumulation both in vitro and in vivo. TPGD was found to perform dual functions in chemotherapy and photothermal therapy. Targeted TPGD combination therapy showed higher rates of glioma cell death and prolonged survival of glioma-bearing rats compared with single doxorubicin or PGD therapy. In conclusion, we developed a potential nanoscale drug delivery system for combined therapy of glioma that can effectively decrease side effects and improve therapeutic effects. PMID- 27189187 TI - Structure of human Cdc45 and implications for CMG helicase function. AB - Cell division cycle protein 45 (Cdc45) is required for DNA synthesis during genome duplication, as a component of the Cdc45-MCM-GINS (CMG) helicase. Despite its essential biological function, its biochemical role in DNA replication has remained elusive. Here we report the 2.1-A crystal structure of human Cdc45, which confirms its evolutionary link with the bacterial RecJ nuclease and reveals several unexpected features that underpin its function in eukaryotic DNA replication. These include a long-range interaction between N- and C-terminal DHH domains, blocking access to the DNA-binding groove of its RecJ-like fold, and a helical insertion in its N-terminal DHH domain, which appears poised for replisome interactions. In combination with available electron microscopy data, we validate by mutational analysis the mechanism of Cdc45 association with the MCM ring and GINS co-activator, critical for CMG assembly. These findings provide an indispensable molecular basis to rationalize the essential role of Cdc45 in genomic duplication. PMID- 27189188 TI - Excessive training impairs the insulin signal transduction in mice skeletal muscles. AB - The main aim of this investigation was to verify the effects of overtraining (OT) on the insulin and inflammatory signaling pathways in mice skeletal muscles. Rodents were divided into control (CT), overtrained by downhill running (OTR/down), overtrained by uphill running (OTR/up), and overtrained by running without inclination (OTR) groups. Rotarod, incremental load, exhaustive, and grip force tests were used to evaluate performance. Thirty-six hours after the grip force test, the extensor digitorum longus (EDL) and soleus were extracted for subsequent protein analyses. The three OT protocols led to similar responses of all performance evaluation tests. The phosphorylation of insulin receptor beta (pIRbeta; Tyr), protein kinase B (pAkt; Ser473), and the protein levels of plasma membrane glucose transporter-4 (GLUT4) were lower in the EDL and soleus after the OTR/down protocol and in the soleus after the OTR/up and OTR protocols. While the pIRbeta was lower after the OTR/up and OTR protocols, the pAkt was higher after the OTR/up in the EDL. The phosphorylation of IkappaB kinase alpha and beta (pIKKalpha/beta; Ser180/181), stress-activated protein kinases/Jun amino-terminal kinases (pSAPK-JNK; Thr183/Tyr185), factor nuclear kappa B (pNFkappaB p65; Ser536), and insulin receptor substrate 1 (pIRS1; Ser307) were higher after the OTR/down protocol, but were not altered after the two other OT protocols. In summary, these data suggest that OT may lead to skeletal muscle insulin signaling pathway impairment, regardless of the predominance of eccentric contractions, although the insulin signal pathway impairment induced in OTR/up and OTR appeared to be muscle fiber-type specific. PMID- 27189189 TI - Early Stage Blood Purification for Paraquat Poisoning: A Multicenter Retrospective Study. AB - OBJECTIVES: To evaluate the efficacy of conservative treatment vs. hemoperfusion (HP) vs. HP + continuous veno-venous hemofiltration (CVVH) for acute Paraquat (PQ) poisoning. METHODS: This was a multicenter retrospective study of patients with PQ poisoning between January 2013 and June 2014. Clinical data and PQ serum levels were collected at baseline and after 24, 48, and 72 h of treatment. RESULTS: Seventy-five, 65, and 43 underwent conservative treatment only (conservative treatment group), conservative treatment + HP (HP group), and conservative treatment + HP + CVVH (HP + CVVH group), respectively. PQ serum levels decreased in all groups after 72 h of treatment (p < 0.001); meanwhile, these values decreased faster in the HP and HP + CVVH groups compared with the conservative treatment group. More importantly, PQ blood levels were significantly lower in the HP + CVVH group compared with the HP group at 24 h (p < 0.05). Sequential organ failure assessment (DeltaSOFA) values in the HP and HP + CVVH groups were significantly lower compared with that obtained for the conservative treatment group (p < 0.05). The 60-day survival rates were 21.3, 43.1 and 46.5%, respectively. Multivariate analysis indicated that age, PQ dose, admission PQ levels, and admission SOFA score were independently associated with mortality. HP and HP + CVVH were protective factors. CONCLUSION: Early HP or HP + CVVH after PQ poisoning could decrease PQ blood levels, alleviate organ damage, and increase survival. PMID- 27189190 TI - The evaluation of three treatments for plantar callus: a three-armed randomised, comparative trial using biophysical outcome measures. AB - BACKGROUND: Callus is one of the most common foot skin complaints experienced by people of all ages. These painful and unsightly lesions often result in disability. The 'gold standard' of treatment is scalpel debridement by a trained specialist; however, people also seek over-the-counter remedies. There is a lack of clinical evidence for the efficacy of such products, which makes selection by patients and practitioners difficult. METHODS: This randomised, three-armed, parallel, comparative trial aimed to test the efficacy of two home treatments for plantar callus using novel, objective outcome measures (skin hydration using the capacitance method; elasticity using negative pressure application; and surface texture using imaging). Additional outcome measures were: size of callus, quality of life (Foot Health Status Questionnaire) and self-reported participant satisfaction and compliance. The results were compared to a podiatry treatment. Participants were randomly allocated to one of three groups: potassium hydroxide (KOH, 40 %); trichloroacetic acid (TCA); and podiatry treatment. Participants were followed for 3 weeks after their initial intervention appointment (days 7, 14 and 21). The primary outcomes were the change from baseline in callus hydration, elasticity, texture, and size at each of the three time points. The secondary outcomes where: change in quality of life 21 days after treatment; resolution of calluses via visual inspection; and participant compliance and perception. RESULTS: Forty-six participants (61 ft) with plantar calluses were recruited. The podiatry treatment showed immediate and significant changes in all objective outcomes, associated foot pain and function (p <0.01). Lesser changes in skin quality and perceived pain and functional benefits occurred with TCA and KOH over 21 days. CONCLUSIONS: This is the first study where objective outcome measures have been used to measure changes in the nature of skin in response to callus treatments. We found significant differences in plantar callus in response to podiatry and two home treatments. The podiatry treatment showed immediate and significant changes in skin and associated foot pain and function. Lesser, but sometimes comparable, changes in skin and perceived pain and functional benefits occurred with TCA and KOH over 21 days. TRIAL REGISTRATION: ISRCTN14751843 : date of registration: 30 April 2015. PMID- 27189193 TI - Grape powder attenuates the negative effects of GLP-1 receptor antagonism by exendin-3 (9-39) in a normoglycemic mouse model. AB - Prediabetes is a condition affecting 35% of US adults and about 50% of US adults age 65+. Foods rich in polyphenols, including flavanols and other flavonoids, have been studied for their putative beneficial effects on many different health conditions including type 2 diabetes mellitus and prediabetes. Studies have shown that some flavanols increase glucagon-like peptide 1 (GLP-1) secretion. GLP-1 is a feeding hormone that increases insulin secretion after carbohydrate consumption, and increased GLP-1 secretion may be responsible for some of the beneficial effects on glycemic control after flavanol consumption. The present study explored the effects of grape powder consumption on metrics of glycemic health in normoglycemic and prediabetic C57BL/6J mice; additionally, the mechanism of action of grape powder polyphenols was investigated. Grape powder significantly reduced (p < 0.01) blood glucose levels following oral glucose gavage after GLP-1 receptor antagonism by exendin-3 (9-39) compared to sugar matched control, indicating that it was able to attenuate the hyperglycemic effects of GLP-1 receptor antagonism. Grape powder was employed in acute (1.6 g grape powder per kg bodyweight) and long-term high fat diet (grape powder incorporated into treatment diets at 5% w/w) feeding studies in normoglycemic and prediabetic (diet-induced obesity) mice; grape powder did not impove glycemic control in these studies versus sugar-matched control. The mechanisms by which grape powder ameliorates the deleterious effects of GLP-1 receptor antagonism warrant further study. PMID- 27189192 TI - Chitosan oligosaccharide induces resistance to Tobacco mosaic virus in Arabidopsis via the salicylic acid-mediated signalling pathway. AB - Chitosan is one of the most abundant carbohydrate biopolymers in the world, and chitosan oligosaccharide (COS), which is prepared from chitosan, is a plant immunity regulator. The present study aimed to validate the effect of COS on inducing resistance to tobacco mosaic virus (TMV) in Arabidopsis and to investigate the potential defence-related signalling pathways involved. Optimal conditions for the induction of TMV resistance in Arabidopsis were COS pretreatment at 50 mg/L for 1 day prior to inoculation with TMV. Multilevel indices, including phenotype data, and TMV coat protein expression, revealed that COS induced TMV resistance in wild-type and jasmonic acid pathway- deficient (jar1) Arabidopsis plants, but not in salicylic acid pathway deficient (NahG) Arabidopsis plants. Quantitative-PCR and analysis of phytohormone levels confirmed that COS pretreatment enhanced the expression of the defence-related gene PR1, which is a marker of salicylic acid signalling pathway, and increased the amount of salicylic acid in WT and jar1, but not in NahG plants. Taken together, these results confirm that COS induces TMV resistance in Arabidopsis via activation of the salicylic acid signalling pathway. PMID- 27189194 TI - Salvage of the proximal femur following pathological fractures involving benign bone tumors. PMID- 27189191 TI - Dietary patterns in the French adult population: a study from the second French national cross-sectional dietary survey (INCA2) (2006-2007). AB - Identification and characterisation of dietary patterns are needed to define public health policies to promote better food behaviours. The aim of this study was to identify the major dietary patterns in the French adult population and to determine their main demographic, socio-economic, nutritional and environmental characteristics. Dietary patterns were defined from food consumption data collected in the second French national cross-sectional dietary survey (2006 2007). Non-negative-matrix factorisation method, followed by a cluster analysis, was implemented to derive the dietary patterns. Logistic regressions were then used to determine their main demographic and socio-economic characteristics. Finally, nutritional profiles and contaminant exposure levels of dietary patterns were compared using ANOVA. Seven dietary patterns, with specific food consumption behaviours, were identified: 'Small eater', 'Health conscious', 'Mediterranean', 'Sweet and processed', 'Traditional', 'Snacker' and 'Basic consumer'. For instance, the Health-conscious pattern was characterised by a high consumption of low-fat and light products. Individuals belonging to this pattern were likely to be older and to have a better nutritional profile than the overall population, but were more exposed to many contaminants. Conversely, individuals of Snacker pattern were likely to be younger, consumed more highly processed foods, had a nutrient-poor profile but were exposed to a limited number of food contaminants. The study identified main dietary patterns in the French adult population with distinct food behaviours and specific demographic, socio-economic, nutritional and environmental features. Paradoxically, for better dietary patterns, potential health risks cannot be ruled out. Therefore, this study demonstrated the need to conduct a risk-benefit analysis to define efficient public health policies regarding diet. PMID- 27189196 TI - Single Molecule Spectroscopy of Monomeric LHCII: Experiment and Theory. AB - We derive approximate equations of motion for excited state dynamics of a multilevel open quantum system weakly interacting with light to describe fluorescence-detected single molecule spectra. Based on the Frenkel exciton theory, we construct a model for the chlorophyll part of the LHCII complex of higher plants and its interaction with previously proposed excitation quencher in the form of the lutein molecule Lut 1. The resulting description is valid over a broad range of timescales relevant for single molecule spectroscopy, i.e. from ps to minutes. Validity of these equations is demonstrated by comparing simulations of ensemble and single-molecule spectra of monomeric LHCII with experiments. Using a conformational change of the LHCII protein as a switching mechanism, the intensity and spectral time traces of individual LHCII complexes are simulated, and the experimental statistical distributions are reproduced. Based on our model, it is shown that with reasonable assumptions about its interaction with chlorophylls, Lut 1 can act as an efficient fluorescence quencher in LHCII. PMID- 27189195 TI - Development of a morphology-based modeling technique for tracking solid-body displacements: examining the reliability of a potential MRI-only approach for joint kinematics assessment. AB - BACKGROUND: Single or biplanar video radiography and Roentgen stereophotogrammetry (RSA) techniques used for the assessment of in-vivo joint kinematics involves application of ionizing radiation, which is a limitation for clinical research involving human subjects. To overcome this limitation, our long term goal is to develop a magnetic resonance imaging (MRI)-only, three dimensional (3-D) modeling technique that permits dynamic imaging of joint motion in humans. Here, we present our initial findings, as well as reliability data, for an MRI-only protocol and modeling technique. METHODS: We developed a morphology-based motion-analysis technique that uses MRI of custom-built solid body objects to animate and quantify experimental displacements between them. The technique involved four major steps. First, the imaging volume was calibrated using a custom-built grid. Second, 3-D models were segmented from axial scans of two custom-built solid-body cubes. Third, these cubes were positioned at pre determined relative displacements (translation and rotation) in the magnetic resonance coil and scanned with a T1 and a fast contrast-enhanced pulse sequences. The digital imaging and communications in medicine (DICOM) images were then processed for animation. The fourth step involved importing these processed images into an animation software, where they were displayed as background scenes. In the same step, 3-D models of the cubes were imported into the animation software, where the user manipulated the models to match their outlines in the scene (rotoscoping) and registered the models into an anatomical joint system. Measurements of displacements obtained from two different rotoscoping sessions were tested for reliability using coefficient of variations (CV), intraclass correlation coefficients (ICC), Bland-Altman plots, and Limits of Agreement analyses. RESULTS: Between-session reliability was high for both the T1 and the contrast-enhanced sequences. Specifically, the average CVs for translation were 4.31 % and 5.26 % for the two pulse sequences, respectively, while the ICCs were 0.99 for both. For rotation measures, the CVs were 3.19 % and 2.44 % for the two pulse sequences with the ICCs being 0.98 and 0.97, respectively. A novel biplanar imaging approach also yielded high reliability with mean CVs of 2.66 % and 3.39 % for translation in the x- and z-planes, respectively, and ICCs of 0.97 in both planes. CONCLUSIONS: This work provides basic proof-of-concept for a reliable marker-less non-ionizing-radiation-based quasi-dynamic motion quantification technique that can potentially be developed into a tool for real-time joint kinematics analysis. PMID- 27189199 TI - Control of corruption, democratic accountability, and effectiveness of HIV/AIDS official development assistance. AB - BACKGROUND: Despite continued global efforts, HIV/AIDS outcomes in developing countries have not made much progress. Poor governance in recipient countries is often seen as one of the reasons for ineffectiveness of aid efforts to achieve stated objectives and desired outcomes. OBJECTIVE: This study examines the impact of two important dimensions of governance - control of corruption and democratic accountability - on the effectiveness of HIV/AIDS official development assistance. DESIGN: An empirical analysis using dynamic panel Generalized Method of Moments estimation was conducted on 2001-2010 datasets. RESULTS: Control of corruption and democratic accountability revealed an independent effect and interaction with the amount of HIV/AIDS aid on incidence of HIV/AIDS, respectively, while none of the two governance variables had a significant effect on HIV/AIDS prevalence. Specifically, in countries with accountability level below -2.269, aid has a detrimental effect on incidence of HIV/AIDS. CONCLUSION: The study findings suggest that aid programs need to be preceded or at least accompanied by serious efforts to improve governance in recipient countries and that democratic accountability ought to receive more critical attention. PMID- 27189198 TI - Chemosensitivity enhancement toward arsenic trioxide by inhibition of histone deacetylase in NB4 cell line. AB - OBJECTIVE: To investigate the cytotoxic effects of suberanilohydroxamic acid (vorinostat) in combination with arsenic trioxide (ATO) on the human NB4 cell line in vitro. METHODS: The rates of cell proliferation following treatment with vorinostat with or without ATO were measured. Flow cytometry of Annexin V/propidium iodide double-stained cells was used to measure apoptosis. Acridine Orange and ethidium bromide staining was used to observe morphological changes characteristic of apoptosis. Western blot analysis was used to measure protein levels. RESULTS: Vorinostat and ATO, alone and in combination, inhibited the proliferation of NB4 cells in a time- and dose-dependent manner and the effect was additive. NB4 cells treated with vorinostat + ATO demonstrated greater levels of apoptosis compared with cells treated with either drug alone. Both vorinostat and ATO alone and in combination resulted in lower levels of promyelocytic leukaemia/retinoic acid receptor alpha fusion protein and increased levels of acetyl-histone H3 and acetyl-histone H4 proteins compared with controls. Vorinostat + ATO resulted in lower levels of Akt protein compared with either drug alone. CONCLUSION: The combination of vorinostat and ATO inhibited cell proliferation, induced apoptosis, and enhanced the chemosensitivity of NB4 cells. The mechanism might be associated with increasing histone acetylation levels as well as downregulation of the Akt signalling pathway. PMID- 27189200 TI - Impact assessment and cost-effectiveness of m-health application used by community health workers for maternal, newborn and child health care services in rural Uttar Pradesh, India: a study protocol. AB - BACKGROUND: An m-health application has been developed and implemented with community health workers to improve their counseling in a rural area of India. The ultimate aim was to generate demand and improve utilization of key maternal, neonatal, and child health services. The present study aims to assess the impact and cost-effectiveness of this project. METHODS/DESIGN: A pre-post quasi experimental design with a control group will be used to undertake difference in differences analysis for assessing the impact of intervention. The Annual Health Survey (2011) will provide pre-intervention data, and a household survey will be carried out to provide post-intervention data.Two community development blocks where the intervention was introduced will be treated as intervention blocks while two controls blocks are selected after matching with intervention blocks on three indicators: average number of antenatal care checkups, percentage of women receiving three or more antenatal checkups, and percentage of institutional deliveries. Two categories of beneficiaries will be interviewed in both areas: women with a child between 29 days and 6 months and women with a child between 12 and 23 months. Propensity score matched samples from intervention and control areas in pre-post periods will be analyzed using the difference in differences method to estimate the impact of intervention in utilization of key services.Bottom-up costing methods will be used to assess the cost of implementing intervention. A decision model will estimate long-term effects of improved health services utilization on mortality, morbidity, and disability. Cost-effectiveness will be assessed in terms of incremental cost per disability adjusted life year averted and cost per unit increase in composite service coverage in intervention versus control groups. CONCLUSIONS: The study will generate significant evidence on impact of the m-health intervention for maternal, neonatal, and child services and on the cost of scaling up m-health technology for accredited social health activists in India. PMID- 27189201 TI - Differential Gene Expression in Menstrual Endometrium From Women With Self Reported Heavy Menstrual Bleeding. AB - Heavy menstrual bleeding (HMB) is a significant social and public health issue for menstruating women. Development of targeted treatments has been limited by poor understanding of local mechanisms underlying HMB. We aimed to determine how gene expression differs in menstrual phase endometrium from women with HMB. Menstrual phase endometrial biopsies were collected from women with (n = 7) and without (n = 10) HMB (regular menstrual cycles, no known pelvic pathology), as well as women with uterine fibroids (n = 7, n = 4 had HMB). Biopsies were analyzed using Illumina Sentrix Human HT12 arrays and data analyzed using "Remove Unwanted Variation-inverse". Ingenuity Pathway Analysis and the Database for Annotation, Visualization and Integrated Discovery v6.7 were used to identify gene pathways, functional gene clusters, and upstream regulators specific to the clinical groupings. Individual genes of interest were examined using quantitative polymerase chain reaction. In total, 829 genes were differentially expressed in one or more comparisons. Significant canonical pathways and gene clusters enriched in controls relative to both HMB and fibroid groups suggest the mechanisms responsible for HMB include modifications of the endometrial inflammatory or infection response. In contrast, differentially expressed genes in women with fibroids suggest modifications of hemoglobin, antigen processing, and the major histocompatibility complex (class II, beta chain) activity. In conclusion, HMB associated with fibroids may be regulated by different endometrial mechanisms from HMB in women without fibroids and from normal menstrual bleeding. These novel data provide numerous testable hypotheses that will advance our understanding of the mechanisms responsible for HMB. PMID- 27189197 TI - Empirical and targeted therapy of candidemia with fluconazole versus echinocandins: a propensity score-derived analysis of a population-based, multicentre prospective cohort. AB - We compared the clinical efficacy of fluconazole and echinocandins in the treatment of candidemia in real practice. The CANDIPOP study is a prospective, population-based cohort study on candidemia carried out between May 2010 and April 2011 in 29 Spanish hospitals. Using strict inclusion criteria, we separately compared the impact of empirical and targeted therapy with fluconazole or echinocandins on 30-day mortality. Cox regression, including a propensity score (PS) for receiving echinocandins, stratified analysis on the PS quartiles and PS-based matched analyses, were performed. The empirical and targeted therapy cohorts comprised 316 and 421 cases, respectively; 30-day mortality was 18.7% with fluconazole and 33.9% with echinocandins (p 0.02) in the empirical therapy group and 19.8% with fluconazole and 27.7% with echinocandins (p 0.06) in the targeted therapy group. Multivariate Cox regression analysis including PS showed that empirical therapy with fluconazole was associated with better prognosis (adjusted hazard ratio 0.38; 95% confidence interval 0.17-0.81; p 0.01); no differences were found within each PS quartile or in cases matched according to PS. Targeted therapy with fluconazole did not show a significant association with mortality in the Cox regression analysis (adjusted hazard ratio 0.77; 95% confidence interval 0.41-1.46; p 0.63), in the PS quartiles or in PS-matched cases. The results were similar among patients with severe sepsis and septic shock. Empirical or targeted treatment with fluconazole was not associated with increased 30-day mortality compared to echinocandins among adults with candidemia. PMID- 27189202 TI - Notch1 Impairs Endothelial Progenitor Cell Bioactivity in Preeclampsia. AB - Aberrant vasculature and endothelial dysfunction on both the maternal and the fetal side are thought to play a role in the pathogenesis of preeclampsia, a hypertensive complication during pregnancy. Endothelial progenitor cells (EPCs) have the capacity for endothelial repair. The Dll4/Notch signaling pathway suppresses the functions of EPCs in the pathogenesis of preeclampsia. Notch1 was found to be one of the specific receptors for ligands of the Delta 4 and play critical roles in angiogenesis. However, the roles of Notch1 with regard to EPCs and preeclampsia have yet to be completely characterized. The aim of this study is to determine whether Notch1 also has a negative influence on the regulation of EPC activity. Accordingly, we analyzed the differences between the preeclampsia group and the control group in terms of the number of EPCs and colony-forming units (CFUs) and their Notch1 expressions. The influence of the Notch1 signaling pathway on functions of EPCs was determined by repeating the assays in the presence of Notch1 downregulation. The number of EPCs and CFUs was significantly lower in patients with preeclampsia compared to healthy controls. Additionally, there was a notable increase in Notch1 expression in EPCs of patients with preeclampsia compared to controls. The downregulation of Notch1 promoted the proliferation, differentiation, migration, and adhesion of EPCs and the ability to form human umbilical vein endothelial cell tubes. These findings suggested that decrease and dysfunction of EPCs may be involved in the pathogenesis of preeclampsia. Inhibition of Notch1, which promoted EPC-mediated angiogenesis in vitro, may be an alternative therapeutic approach to promoting vasculogenesis in patients with preeclampsia. PMID- 27189203 TI - Clinical and gender differences in heart transplant recipients in the NEW HEART study. AB - BACKGROUND: Little attention has focused on gender differences in cardiac comorbidities and outcomes in patients undergoing orthotropic heart transplant. OBJECTIVE: The objective of this study was to investigate gender differences at baseline and during follow-up among heart transplant patients. METHODS: An observational cohort within the NEW HEART study was evaluated to determine gender differences in relation to age, coexisting cardiac comorbidities, and outcomes. Differences were assessed by t-test, Fisher's exact test, and logistic regression analysis. RESULTS: Male transplant recipients ( n = 238) were significantly older than female recipients ( n = 92), with a greater percentage over 60 years of age (45% vs. 24%, p = 0.0006). Males were more likely to have hypertension (63% vs. 49%, p = 0.034), dyslipidemia (62% vs. 45%, p = 0.006), a history of smoking (52% vs. 35%, p = 0.009), and diabetes (42% vs. 21%, p = 0.0002). Analysis of endomyocardial biopsies obtained during the 1-year follow-up period demonstrated that women averaged more episodes of acute rejection than men (3.9 vs. 3.0, p = 0.009). While most episodes of rejection were mild, women were more likely than men to have episodes of moderate or severe rejection (14% vs. 5%, p = 0.012) and to be hospitalized for acute rejection (15% vs. 6%, p = 0.013). There were no significant differences in mortality. CONCLUSIONS: Men were more likely than women to be older and to have diabetes, dyslipidemia, hypertension, and a history of smoking. Women were more likely to experience moderate or severe allograft rejection and to be hospitalized for acute rejection. Future investigation of the reasons for these gender differences is warranted and may improve clinical care of women undergoing cardiac transplantation. PMID- 27189204 TI - Winogradskyella sediminis sp. nov., isolated from marine sediment. AB - A Gram-stain-negative, rod-shaped, yellow-pigmented, gliding bacterial strain, designated S5-23-3T, was isolated from a sediment sample of the Yellow Sea in China. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain S5-23-3T was related to the genus Winogradskyella and had highest 16S rRNA gene sequence similarities with Winogradskyella arenosi JCM 15527T (97.6 %), Winogradskyella rapida CECT 7392T (97.4 %) and Winogradskyella undariae KCTC 32261T (97.2 %). The predominant cellular fatty acids were iso-C15 : 0, iso-C15 : 1 G, iso-C15 : 0 3-OH and iso-C17 : 0 3-OH. Strain S5-23-3T contained MK-6 as the predominant menaquinone. The polar lipid profile contained phosphatidylethanolamine, two aminolipids, one aminoglycolipid, one aminophospholipid, one unidentified phospholipid and seven unidentified polar lipids. The genomic DNA G+C content of strain S5-23-3T was 36.1 mol%. Combined data from phenotypic, chemotaxonomic, phylogenetic and DNA-DNA relatedness studies demonstrated that strain S5-23-3T is a representative of a novel species of the genus Winogradskyella, for which the name Winogradskyellasediminis sp. nov. (type strain S5-23-3T=LMG 28075T=DSM 28134T) is proposed. PMID- 27189206 TI - Pressure-induced magnetic transitions with change of the orbital configuration in dimerised systems. AB - We suggest a possible scenario for magnetic transition under pressure in dimerised systems where electrons are localised on molecular orbitals. The mechanism of transition is not related with competition between kinetic energy and on-site Coulomb repulsion as in Mott-Hubbard systems, or between crystal field splitting and intra-atomic exchange as in classical atomic spin-state transitions. Instead, it is driven by the change of bonding-antibonding splitting on part of the molecular orbitals. In the magnetic systems with few half-filled molecular orbitals external pressure may result in increase of the bonding antibonding splitting and localise all electrons on low-lying molecular orbitals suppressing net magnetic moment of the system. We give examples of the systems, where this or inverse transition may occur and by means of ab initio band structure calculations predict that it can be observed in alpha-MoCl4 at pressure P ~ 11 GPa. PMID- 27189207 TI - Spin-crossover complex encapsulation within a magnetic metal-organic framework. AB - The solid-state incorporation of a mononuclear iron(iii) complex within the pores of a magnetic 3D metal-organic framework (MOF) in a single crystal to single crystal process leads to the formation of a new hybrid material showing both a guest-dependent long-range magnetic ordering and a spin-crossover (SCO) behaviour. PMID- 27189205 TI - Regeneration of hair cells in the mammalian vestibular system. AB - Hair cells regenerate throughout the lifetime of non-mammalian vertebrates, allowing these animals to recover from hearing and balance deficits. Such regeneration does not occur efficiently in humans and other mammals. Thus, balance deficits become permanent and is a common sensory disorder all over the world. Since Forge and Warchol discovered the limited spontaneous regeneration of vestibular hair cells after gentamicininduced damage in mature mammals, significant efforts have been exerted to trace the origin of the limited vestibular regeneration in mammals after hair cell loss. Moreover, recently many strategies have been developed to promote the hair cell regeneration and subsequent functional recovery of the vestibular system, including manipulating the Wnt, Notch and Atoh1. This article provides an overview of the recent advances in hair cell regeneration in mammalian vestibular epithelia. Furthermore, this review highlights the current limitations of hair cell regeneration and provides the possible solutions to regenerate functional hair cells and to partially restore vestibular function. PMID- 27189208 TI - Small area-level variation in the incidence of psychotic disorders in an urban area in France: an ecological study. AB - PURPOSE: We sought to determine whether significant variation in the incidence of clinically relevant psychoses existed at an ecological level in an urban French setting, and to examine possible factors associated with this variation. We aimed to advance the literature by testing this hypothesis in a novel population setting and by comparing a variety of spatial models. METHODS: We sought to identify all first episode cases of non-affective and affective psychotic disorders presenting in a defined urban catchment area over a 4 years period, over more than half a million person-years at-risk. Because data from geographic close neighbourhoods usually show spatial autocorrelation, we used for our analyses Bayesian modelling. We included small area neighbourhood measures of deprivation, migrants' density and social fragmentation as putative explanatory variables in the models. RESULTS: Incidence of broad psychotic disorders shows spatial patterning with the best fit for models that included both strong autocorrelation between neighbouring areas and weak autocorrelation between areas further apart. Affective psychotic disorders showed similar spatial patterning and were associated with the proportion of migrants/foreigners in the area (inverse correlation). In contrast, non-affective psychoses did not show spatial patterning. CONCLUSIONS: At ecological level, the variation in the number of cases and the factors that influence this variation are different for non affective and affective psychotic disorders. Important differences in results compared with previous studies in different settings-point to the importance of the context and the necessity of further studies to understand these differences. PMID- 27189209 TI - Family, friends, and 12-month PTSD among African Americans. AB - PURPOSE: Despite a growing literature on the influence of social support on mental health, little is known about the relationship between social support and specific psychiatric disorders for African Americans, such as PTSD. This study investigated the relationship between social support, negative interaction with family and 12-month PTSD among African Americans. METHODS: Analyses were based on a nationally representative sample of African Americans from the National Survey of American Life (n = 3315). Social support variables included emotional support from family, frequency of contact with family and friends, subjective closeness with family and friends, and negative interactions with family. RESULTS: Results indicated that emotional support from family is negatively associated with 12 month PTSD while negative interaction with family is predictive of 12-month PTSD. Additionally, a significant interaction indicated that high levels of subjective closeness to friends could offset the impact of negative family interactions on 12-month PTSD. CONCLUSIONS: Overall, study results converged with previously established findings indicating that emotional support from family is associated with 12-month PTSD, while, negative interaction with family is associated with increased risk of 12-month PTSD. The findings are discussed in relation to prior research on the unique association between social support and mental health among African Americans. PMID- 27189210 TI - Thrombin-unique coagulation system protein with multifaceted impacts on cancer and metastasis. AB - The association between blood coagulation and cancer development is well recognized. Thrombin, the pleiotropic enzyme best known for its contribution to fibrin formation and platelet aggregation during vascular hemostasis, may also trigger cellular events through protease-activated receptors, PAR-1 and PAR-4, leading to cancer progression. Our pioneering findings provided evidence that thrombin contributes to cancer metastasis by increasing adhesive potential of malignant cells. However, there is evidence that thrombin regulates every step of cancer dissemination: (1) cancer cell invasion, detachment from primary tumor, migration; (2) entering the blood vessel; (3) surviving in vasculature; (4) extravasation; (5) implantation in host organs. Recent studies have provided new molecular data about thrombin generation in cancer patients and the mechanisms by which thrombin contributes to transendothelial migration, platelet/tumor cell interactions, angiogenesis, and other processes. Though a great deal is known regarding the role of thrombin in cancer dissemination, there are new data for multiple thrombin-mediated events that justify devoting focus to this topic with a comprehensive approach. PMID- 27189212 TI - Bosentan Pharmacokinetics in Pediatric Patients with Pulmonary Arterial Hypertension: Comparison of Dried Blood Spot and Plasma Analysis. AB - FUTURE-3, a phase III pediatric pharmacokinetic (PK) trial conducted to compare 2 bosentan dosing regimens in 64 patients with pulmonary arterial hypertension, offered the opportunity to compare dried blood spot (DBS)-derived data to plasma data. Bosentan PK parameters obtained with both methods were compared by the geometric mean ratio (GMR; DBS/plasma) and its 90% CI after correction for the blood-to-plasma partition ratio (0.6). Bosentan GMRs were 1.10 (1.03, 1.16) and 1.12 (1.04, 1.20) for AUCtau and Cmax, respectively. Bosentan concentrations measured by DBS were therefore good estimations of bosentan plasma concentrations. DBS can be considered a valid alternative to bosentan assessed in plasma. PMID- 27189211 TI - Improving microRNA target prediction with gene expression profiles. AB - BACKGROUND: Mammalian genomes encode for thousands of microRNAs, which can potentially regulate the majority of protein-coding genes. They have been implicated in development and disease, leading to great interest in understanding their function, with computational methods being widely used to predict their targets. Most computational methods rely on sequence features, thermodynamics, and conservation filters; essentially scanning the whole transcriptome to predict one set of targets for each microRNA. This has the limitation of not considering that the same microRNA could have different sets of targets, and thus different functions, when expressed in different types of cells. RESULTS: To address this problem, we combine popular target prediction methods with expression profiles, via machine learning, to produce a new predictor: TargetExpress. Using independent data from microarrays and high-throughput sequencing, we show that TargetExpress outperforms existing methods, and that our predictions are enriched in functions that are coherent with the added expression profile and literature reports. CONCLUSIONS: Our method should be particularly useful for anyone studying the functions and targets of miRNAs in specific tissues or cells. TargetExpress is available at: http://targetexpress.ceiabreulab.org/ . PMID- 27189213 TI - Prognostic factors in infective endocarditis in general hospitals in the Netherlands. AB - INTRODUCTION: Despite advances in treatment, infective endocarditis (IE) still ranks amongst the most lethal infectious diseases. We sought to determine prognostic factors in general hospitals in the Netherlands as research in this setting is scarce. RESULTS: Between 2004 and 2011, we identified 216 cases of IE, 30.1 % of which were prosthetic valve IE. This leads to an annual incidence of IE of 5.7 new cases per 100,000 persons per year. Women were less likely to undergo surgical intervention (OR = 1.96, 95 % CI 1.06-3.61, p = 0.031). Also, ageing was an independent prognostic factor for not receiving surgery in a multivariate analysis (annual OR = 1.04, 95 % CI 1.02-1.06, p < 0.001). Female sex was a prognostic factor for mortality (OR = 2.35, 95 % CI 1.29-4.28, p = 0.005). Age was also an independent prognostic factor for mortality (OR = 1.05, 95% CI 1.03 1.08, p < 0.001). Conservative treatment was a prognostic factor for mortality (OR = 3.39, 95 % CI 1.80-6.38, p < 0.001) whereas surgical intervention was an independent prognostic factor for adverse events (OR = 3.03, 95% CI 1.64-5.55, p < 0.001). Staphylococcus aureus was an independent prognostic factor for adverse events (OR = 2.05, 95 % CI 1.10-3.84, p = 0.024) but not for mortality. CONCLUSION: This study shows that endocarditis in general hospitals has a high rate of morbidity and mortality. Even when treated, it ranks as one of the most lethal infectious diseases in the Netherlands, especially in women and the elderly. PMID- 27189214 TI - The predictive value of conventional surgical risk scores for periprocedural mortality in percutaneous mitral valve repair. AB - BACKGROUND: Surgical risk scores are used to identify high-risk patients for surgical mitral valve repair. There is no scoring system to estimate the mortality risk for patients undergoing percutaneous treatment. The aim of this analysis is to evaluate the predictive value of the EuroSCOREs and the Society of Thoracic Surgeons Predicted Risk of Mortality Score (STS) for periprocedural mortality in percutaneous edge-to-edge mitral valve repair. METHODS: From 2009 to 2013, 136 high-risk patients were included who underwent 143 procedures. Observed periprocedural mortality was compared with predicted mortality using the logistic EuroSCORE, EuroSCORE II and STS. The predictive value was analysed by receiver operating characteristic curves for each score. RESULTS: Observed periprocedural mortality was 3.5 %. The predicted surgical mortality risk was: 23.1 +/- 15.7 % for the logistic EuroSCORE, 9.6 +/- 7.7 % for the EuroSCORE II and 13.2 +/- 8.2 % for the STS. The predictive value estimated by the area under the curve was: 0.55, 0.54 and 0.65 for the logistic EuroSCORE, EuroSCORE II and STS respectively. Severe pulmonary hypertension and acute procedural success were significant predictive parameters in univariate analysis. CONCLUSION: Contemporary surgical scores do not adequately predict periprocedural mortality for high-risk patients undergoing edge-to-edge mitral valve repair, but they can be used to help decision-making in the selection process for this procedure. PMID- 27189215 TI - Pulmonary hypertension: the importance of a multidisciplinary approach. PMID- 27189216 TI - Echocardiographic findings associated with mortality ortransplant in patients with pulmonary arterial hypertension:A systematic review and meta-analysis. AB - BACKGROUND: Identification of patients at risk of deterioration is essential to guide clinical management in pulmonary arterial hypertension (PAH). This study aims to provide a comprehensive overview of well-investigated echocardiographic findings that are associated with clinical deterioration in PAH. METHODS: MEDLINE and EMBASE databases were systematically searched for longitudinal studies published by April 2015 that reported associations between echocardiographic findings and mortality, transplant or clinical worsening. Meta-analysis using random effect models was performed for echocardiographic findings investigated by four or more studies. In case of statistical heterogeneity a sensitivity analysis was conducted. RESULTS: Thirty-seven papers investigating 51 echocardiographic findings were included. Meta-analysis of univariable hazard ratios (HRs) and sensitivity analysis showed that presence of pericardial effusion (pooled HR 1.70; 95 % CI 1.44-1.99), right atrial area (pooled HR 1.71; 95 % CI 1.38-2.13) and tricuspid annular plane systolic excursion (TAPSE; pooled HR 1.72; 95 % CI 1.34-2.20) were the most well-investigated and robust predictors of mortality or transplant. CONCLUSIONS: This meta-analysis substantiates the clinical yield of specific echocardiographic findings in the prognostication of PAH patients in day to-day practice. In particular, pericardial effusion, right atrial area and TAPSE are of prognostic value. PMID- 27189222 TI - TFE3-Expressing Perivascular Epithelioid Cell Neoplasm (PEComa) of the Sella Turcica. AB - We report a primary central nervous system (CNS) perivascular epithelioid cell tumor (PEComa) in a middle-aged female patient. The tumor occurred in suprasellar location with secondary extension into the sella turcica. The patient presented with intracranial hemorrhage and an altered level of consciousness. The tumor had morphologic features matching those of other previously described TFE3 translocated PEComas, including epithelioid morphology, diffuse and strong nuclear immunoreactivity for TFE3, and minimal staining with myoid markers. The TFE3 break-apart FISH testing showed a slight splitting of one of the TFE3 signals in 49.5 % of nuclei. This case illustrates that PEComas should be added to the growing list of mesenchymal tumors that can be encountered in the CNS and specifically in the vicinity of the pituitary gland. The recognition of this entity is of significance given their underlying pathogenesis and possible management implications. PMID- 27189223 TI - Site specific polarization transfer from a hyperpolarized ligand of dihydrofolate reductase. AB - Protein-ligand interaction is often characterized using polarization transfer by the intermolecular nuclear Overhauser effect (NOE). For such NOE experiments, hyperpolarization of nuclear spins presents the opportunity to increase the spin magnetization, which is transferred, by several orders of magnitude. Here, folic acid, a ligand of dihydrofolate reductase (DHFR), was hyperpolarized on (1)H spins using dissolution dynamic nuclear polarization (D-DNP). Mixing hyperpolarized ligand with protein resulted in observable increases in protein (1)H signal predominantly in the methyl group region of the spectra. Using (13)C single quantum selection in a series of one-dimensional spectra, the carbon chemical shift ranges of the corresponding methyl groups can be elucidated. Signals observed in these hyperpolarized spectra could be confirmed using 3D isotope filtered NOESY spectra, although the hyperpolarized spectra were obtained in single scans. By further correlating the signal intensities observed in the D DNP experiments with the occurrence of short distances in the crystal structure of the protein-ligand complex, the observed methyl proton signals could be matched to the chemical shifts of six amino acids in the active site of DHFR folic acid binary complex. These data demonstrate that (13)C chemical shift selection of protein resonances, combined with the intrinsic selectivity towards magnetization originating from the initially hyperpolarized spins, can be used for site specific characterization of protein-ligand interactions. PMID- 27189225 TI - Traditional, complementary and alternative medicine use by HIV patients a decade after public sector antiretroviral therapy roll out in South Africa: a cross sectional study. AB - BACKGROUND: The roll out of antiretroviral therapy in the South African public health sector in 2004 was preceded by the politicisation of HIV-infection which was used to promote traditional medicine for the management of HIV/AIDS. One decade has passed since; however, questions remain on the extent of the use of traditional, complementary and alternative medicine (TCAM) by HIV-infected patients. This study therefore aimed at investigating the prevalence of the use of African traditional medicine (ATM), complementary and alternative medicines (CAM) by adult patients in the eThekwini and UThukela Health Districts, South Africa. METHODS: A cross- sectional study was carried out at 8 public health sector antiretroviral clinics using interviewer-administered semi-structured questionnaires. These were completed from April to October 2014 by adult patients who had been on antiretroviral therapy (ART) for at least three months. Use of TCAM by patients was analysed by descriptive statistics using frequency and percentages with standard error. Where the associated relative error was equal or greater to 0.50, the percentage was rejected as unstable. A p-value <0.05 was estimated as statistically significant. RESULTS: The majority of the 1748 participants were Black Africans (1685/1748, 96.40 %, SE: 0.00045), followed by Coloured (39/1748, 2.23 %, SE: 0.02364), Indian (17/1748, 0.97 %, SE: 0.02377), and Whites (4/1748, 0.23 %, SE: 0.02324), p < 0.05. The prevalence of ATM use varied prior to (382/1748, 21.85 %) and after ART initiation (142/1748, 8.12 %), p <0.05, specifically by Black African females both before (14.41 %) and after uptake (5.49 %), p < 0.05. Overall, 35 Black Africans, one Coloured and one Indian (37/1748, 2.12 %) reported visiting CAM practitioners for their HIV condition and related symptoms post ART. CONCLUSION: Despite a progressive implementation of a successful antiretroviral programme over the first decade of free antiretroviral therapy in the South African public health sector, the use of TCAM is still prevalent amongst a small percentage of HIV infected patients attending public healthcare sector antiretroviral clinics. Further research is needed to explore reasons for use and health benefits or risks experienced by the minority that uses both conventional antiretroviral therapy with TCAM. PMID- 27189226 TI - Protection and immunological study on two tetraspanin-derived vaccine candidates against schistosomiasis japonicum. AB - Tetraspanins (TSPs) are proteins found on the surface of helminth parasites of the genus Schistosoma and are regarded as potentially protective antigens. The large extracellular loop of Schistosoma mansoni tetraspanin-2, Sm-TSP-2, when fused to a thioredoxin partner and formulated with Freund's adjuvants, has been shown to be an efficacious vaccine against murine schistosomiasis. It is well recognized that CD4(+) T-cell-dependent immunity might play an important role against schistosomes; however, the contribution of CD8(+) T cells against multicellular pathogen is still uncertain. The exogenous protein-pulsed dendritic cells (DCs) can easily activate CD4(+) T cells response, while CD8(+) T cells response was relatively difficult to be induced. In this study, we evaluated the immunogenicity of TSP2HD antigen (hydrophilic domain of the S. japonicum tetraspanin-2) and TAT (the protein transduction domain of HIV-1)-coupled TSP2HD protein. As TAT-fused protein could promote major histocompatibility complex class I-dependent antigen presentation in vitro, TAT-TSP2HD-pulsed DCs induced stronger proliferation of schistosome-specific CD8(+) T cells compared with DCs incubated with TSP2HD alone. Vaccination with TAT-TSP2HD-pulsed DCs in vivo could improve disease outcome in S. japonicum-infected mice and was slightly superior to vaccination with DCs treated with TSP2HD. In summary, these data showed that TAT fusion proteins could help activate CD8(+) cells and Th1 cells and provide part protection against schistosome. PMID- 27189224 TI - Circulating long non-coding RNAs in cancer: current status and future perspectives. AB - Long non-coding RNAs (lncRNAs) comprise a diverse class of RNA transcripts >200 nucleotides in length with limited protein-coding potential. In addition to their possible role in cancer biology, circulating lncRNAs have emerged as a new class of promising cancer biomarkers, with independent studies demonstrating the feasibility of their use as tools in the diagnosis and prognosis of different types of malignancies and for predicting and possibly monitoring treatment response. However, critical issues are represented by nonuniform sample choice, handling and processing, blood cell contamination during sample preparation and the lack of consensus regarding data normalization. In this review, we discuss the value of circulating lncRNAs in the clinical setting, particularly with respect to their possible implementation as diagnostic and prognostic markers in cancer. Although the great potential of circulating lncRNAs as cancer biomarkers would be an important development in disease management, both intrinsic and extrinsic factors that may affect their measurement have not been fully characterized. Moreover, the clinical significance of circulating lncRNA may not be proven without a global consensus regarding procedures and standardized protocols for their detection. PMID- 27189227 TI - Postinfectious and sporadic functional gastrointestinal disorders have different prevalences and rates of overlap: results from a controlled cohort study 3 years after acute giardiasis. AB - BACKGROUND: Irritable bowel syndrome (IBS) is a common complication following gastroenteritis, and a high prevalence of postgiardiasis IBS has previously been reported. This study aims to investigate the prevalence, adjusted relative risk (RRadj), and overlap of different functional gastrointestinal disorders (FGID) according to Rome III criteria following infection with Giardia lamblia. METHODS: All patients >=18 years of age with verified giardiasis during an outbreak in 2004, and a control group matched by age and gender, were mailed a questionnaire 3 years later. KEY RESULTS: The prevalence of functional dyspepsia (FD) was 25.9% in the exposed and 6.9% in the control group, RRadj: 3.9 (95% confidence intervals [CI]: 3.1-4.8). The prevalence of IBS was 47.9% and 14.3%, respectively, with RRadj: 3.4 (95% CI: 3.0-3.8). Prevalence of other gastrointestinal symptoms ranged from 70.0% vs 39.7% for bloating (RRadj: 1.8) to 8.3% vs 2.9% for nausea (RRadj: 3.0) in the Giardia and the control group, respectively. Among individuals fulfilling criteria for IBS 44% in the exposed group and 29% in the control group also fulfilled criteria for FD. IBS subtypes based on Rome III criteria (stool consistency) showed poor agreement with subtypes based on frequency of bowel movements (Kappa-values: 0.17 and 0.27). CONCLUSIONS & INFERENCES: There were high prevalences and RRs of IBS, FD and other gastrointestinal symptoms following acute giardiasis, and a high degree of overlap between the disorders. The agreement between different IBS subtype criteria varied, and there were also differences between the exposed and control group. PMID- 27189229 TI - Potato intake and incidence of hypertension: results from three prospective US cohort studies. AB - OBJECTIVE: To determine whether higher intake of baked or boiled potatoes, French fries, or potato chips is associated with incidence of hypertension. DESIGN: Prospective longitudinal cohort studies. SETTING: Healthcare providers in the United States. PARTICIPANTS: 62 175 women in Nurses' Health Study, 88 475 women in Nurses' Health Study II, and 36 803 men in Health Professionals Follow-up Study who were non-hypertensive at baseline. MAIN OUTCOME MEASURE: Incident cases of hypertension (self reported diagnosis by healthcare provider). RESULTS: Compared with consumption of less than one serving a month, the random effects pooled hazard ratios for four or more servings a week were 1.11 (95% confidence interval 0.96 to 1.28; P for trend=0.05) for baked, boiled, or mashed potatoes, 1.17 (1.07 to 1.27; P for trend=0.001) for French fries, and 0.97 (0.87 to 1.08; P for trend=0.98) for potato chips. In substitution analyses, replacing one serving a day of baked, boiled, or mashed potatoes with one serving a day of non starchy vegetables was associated with decreased risk of hypertension (hazard ratio 0.93, 0.89 to 0.96). CONCLUSION: Higher intake of baked, boiled, or mashed potatoes and French fries was independently and prospectively associated with an increased risk of developing hypertension in three large cohorts of adult men and women. PMID- 27189228 TI - Selective Detection of RGD-Integrin Binding in Cancer Cells Using Tip Enhanced Raman Scattering Microscopy. AB - Ligand-receptor interactions play important roles in many biological processes. Cyclic arginine-glycine-aspartic acid (RGD) containing peptides are known to mimic the binding domain of extracellular matrix protein fibronectin and selectively bind to a subset of integrin receptors. Here we report the tip enhanced Raman scattering (TERS) detection of RGD-functionalized nanoparticles bound to integrins produces a Raman scattering signal specific to the bound protein. These results demonstrate that this method can detect and differentiate between two different integrins (alpha5beta1 and alphavbeta3) bound to RGD conjugated gold nanoparticles both on surfaces and in a cancer cell membrane. In situ measurements of RGD nanoparticles bound to purified alpha5beta1 and alphavbeta3 receptors attached to a glass surface provide reference spectra for a multivariate regression model. The TERS spectra observed from nanoparticles bound to cell membranes are analyzed using this regression model and the identity of the receptor can be determined. The ability to distinguish between receptors in the cell membrane provides a new tool to chemically characterize ligand-receptor recognition at molecular level and provide chemical perspective on the molecular recognition of membrane receptors. PMID- 27189230 TI - Toward a world of theranostic medication: Programming biological sentinel systems for therapeutic intervention. AB - Theranostic systems support diagnostic and therapeutic functions in a single integrated entity and enable precise spatiotemporal control of the generation of therapeutic molecules according to the individual patient's disease state, thereby maximizing the therapeutic outcome and minimizing side effects. These systems can also incorporate reporter systems equipped with a disease-sensing module that can be used to estimate the efficacy of treatment in vivo. Among these reporter systems, biological sentinel systems, such as viruses, bacteria, and mammalian cells, have great potential for use in the development of novel theranostic systems because of their ability to sense a variety of disease markers and secrete various therapeutic molecules. Furthermore, recent advances in biotechnology and synthetic biology have made it possible to treat these biological systems as true programmable entities capable of conducting complex operations, to accurately identify each individual patient's disease state. In this review, we introduce the basic design principles of these rapidly expanding classes of biological sentinel system-based theranostic agents, with a focus on recent advances, and we also discuss potential enabling technologies that can further improve these systems and provide more sophisticated therapeutic interventions in the near future. In addition, we consider the possibility of synergistic use of theranostic agents that use different modalities and discuss the prospects for next-generation theranostic agents. PMID- 27189231 TI - Engineering erythrocytes for the modulation of drugs' and contrasting agents' pharmacokinetics and biodistribution. AB - Pharmacokinetics, biodistribution, and biological activity are key parameters that determine the success or failure of therapeutics. Many developments intended to improve their in vivo performance, aim at modulating concentration, biodistribution, and targeting to tissues, cells or subcellular compartments. Erythrocyte-based drug delivery systems are especially efficient in maintaining active drugs in circulation, in releasing them for several weeks or in targeting drugs to selected cells. Erythrocytes can also be easily processed to entrap the desired pharmaceutical ingredients before re-infusion into the same or matched donors. These carriers are totally biocompatible, have a large capacity and could accommodate traditional chemical entities (glucocorticoids, immunossuppresants, etc.), biologics (proteins) and/or contrasting agents (dyes, nanoparticles). Carrier erythrocytes have been evaluated in thousands of infusions in humans proving treatment safety and efficacy, hence gaining interest in the management of complex pathologies (particularly in chronic treatments and when side-effects become serious issues) and in new diagnostic approaches. PMID- 27189232 TI - Branched polyesters: Preparative strategies and applications. AB - In the last 20years, the availability of precision chemical tools (e.g. controlled/living polymerizations, 'click' reactions) has determined a step change in the complexity of both the macromolecular architecture and the chemical functionality of biodegradable polyesters. A major part in this evolution has been played by the possibilities that controlled macromolecular branching offers in terms of tailored physical/biological performance. This review paper aims to provide an updated overview of preparative techniques that derive hyperbranched, dendritic, comb, grafted polyesters through polycondensation or ring-opening polymerization mechanisms. PMID- 27189235 TI - Terminal alpha-d-mannosides are critical during sea urchin gastrulation. AB - The sea urchin embryo is a United States National Institutes of Health (NIH) designated model system to study mechanisms that may be involved in human health and disease. In order to examine the importance of high-mannose glycans and polysaccharides in gastrulation, Lytechinus pictus embryos were incubated with Jack bean alpha-mannosidase (EC 3.2.1.24), an enzyme that cleaves terminal mannose residues that have alpha1-2-, alpha1-3-, or alpha1-6-glycosidic linkages. The enzyme treatment caused a variety of morphological deformations in living embryos, even with alpha-mannosidase activities as low as 0.06 U/ml. Additionally, formaldehyde-fixed, 48-hour-old L. pictus embryos were microdissected and it was demonstrated that the adhesion of the tip of the archenteron to the roof of the blastocoel in vitro is abrogated by treatment with alpha-mannosidase. These results suggest that terminal mannose residues are involved in the adhesion between the archenteron and blastocoel roof, perhaps through a lectin-like activity that is not sensitive to fixation. PMID- 27189234 TI - Gross anatomical classification of the courses of the human lingual artery. AB - PURPOSE: There are many reports on the variation of origin site of the lingual artery branching from the external carotid artery. However, there are few reports systematically investigating the course of the lingual artery in detail from branching site to the body of tongue. The purpose of this study is to classify systematically the courses of the lingual artery including variations. METHODS: Using 111 body sides of 63 Japanese cadavers for dissection practices, the lingual artery and the surrounding structures were investigated gross anatomically. RESULTS: The courses of the lingual artery were classified into five types based on the positional relationships with the hyoglossus and the mylohyoid as follows; type M: coursing medial to the hyoglossus (normal course, 104 sides), type L: coursing lateral to the hyoglossus (2 sides), type T: transferring its course from lateral to medial to the hyoglossus (2 sides), type P: penetrating the mylohyoid (2 sides), and type C: the coinciding of types M and P (1 side). Types L, T, P, and C were considered to be variant lingual arteries. Types M and T, type L, and type P arose from the external carotid, facial, and submental arteries, respectively. In types L and P, adding to the variant lingual artery, the remnant of the normal lingual artery was also observed. CONCLUSION: The present study provides detailed information on the courses of lingual artery which will be of clinical importance especially in the super-selective arterial angiography. PMID- 27189233 TI - A systematic review of the use of the Consolidated Framework for Implementation Research. AB - BACKGROUND: In 2009, Damschroder et al. developed the Consolidated Framework for Implementation Research (CFIR), which provides a comprehensive listing of constructs thought to influence implementation. This systematic review assesses the extent to which the CFIR's use in implementation research fulfills goals set forth by Damschroder et al. in terms of breadth of use, depth of application, and contribution to implementation research. METHODS: We searched Scopus and Web of Science for publications that cited the original CFIR publication by Damschroder et al. (Implement Sci 4:50, 2009) and downloaded each unique result for review. After applying exclusion criteria, the final articles were empirical studies published in peer-review journals that used the CFIR in a meaningful way (i.e., used the CFIR to guide data collection, measurement, coding, analysis, and/or reporting). A framework analysis approach was used to guide abstraction and synthesis of the included articles. RESULTS: Twenty-six of 429 unique articles (6 %) met inclusion criteria. We found great breadth in CFIR application; the CFIR was applied across a wide variety of study objectives, settings, and units of analysis. There was also variation in the method of included studies (mixed methods (n = 13); qualitative (n = 10); quantitative (n = 3)). Depth of CFIR application revealed some areas for improvement. Few studies (n = 3) reported justification for selection of CFIR constructs used; the majority of studies (n = 14) used the CFIR to guide data analysis only; and few studies investigated any outcomes (n = 11). Finally, reflections on the contribution of the CFIR to implementation research were scarce. CONCLUSIONS: Our results indicate that the CFIR has been used across a wide range of studies, though more in-depth use of the CFIR may help advance implementation science. To harness its potential, researchers should consider how to most meaningfully use the CFIR. Specific recommendations for applying the CFIR include explicitly justifying selection of CFIR constructs; integrating the CFIR throughout the research process (in study design, data collection, and analysis); and appropriately using the CFIR given the phase of implementation of the research (e.g., if the research is post implementation, using the CFIR to link determinants of implementation to outcomes). PMID- 27189236 TI - Effect of Prestenting on Success and Complication Rates of Ureterorenoscopy in Pediatric Population. AB - INTRODUCTION: In this study, we aimed to investigate the effect of prestenting on success and complication rates of pediatric ureterorenoscopy (URS) procedures. PATIENTS AND METHODS: We retrospectively analyzed the data of 251 pediatric URS cases. Forty-seven of the patients were prestented. Success and complication rates of the prestented and nonprestented groups were compared and further analysis was performed with respect to stone location (renal vs ureteral) and size (7-mm cutoff). Multivariate analysis was performed to define factors associated with success rates. RESULTS: Mean age of the population was 8.9 years. Success rate of the entire population was 80.5% and significant difference between prestented and nonprestented groups was detected (91.5% vs 77.9%, p = 0.04). Higher success rates of the prestented group were also observed in ureteral stones (94.1% vs 79.5%, p = 0.04) and stones >7 mm (84.6% vs 74.1%, p = 0.72). Prestented group showed higher success rates in kidney stones, but the difference was insignificant (84.6% vs 74.1%, p = 0.72). Prestenting was also identified as an independent predictor of success in multivariate analysis. Complication rate in the prestented group was also lower, but the difference was not significant (8.5% vs 14.7%, p = 0.347). CONCLUSIONS: Prestenting was found to increase the success rate of URS in cases of larger stones and ureteral stones in pediatric population. Prestenting also provides lower, but insignificant, complication rates. However, this procedure also has significant disadvantages. Based on the results of current study, we cannot recommend routine prestenting in pediatric cases. Instead, we recommend an attempt to treat the stone in the first session and place a stent in case of failed procedure to utilize potential benefits of prestenting while avoiding disadvantages. PMID- 27189237 TI - User value and usability of a web-based mindfulness intervention for families living with mental health problems. AB - Mental health problems affect the patients and their families, who may also need therapeutic interventions. Mindfulness interventions have shown beneficial health effects for clinical and healthy populations. A web-based mindfulness intervention was tailored to address families' needs of support and tested in a pilot intervention study. The aim of this study was to explore the participants' experiences of using an 8-week web-based mindfulness programme in terms of user value and usability. Qualitative semi-structured interviews were carried out over the phone (Spring 2015, Sweden) with 15 randomly selected participants after the 3-month follow-up as part of the pilot study. Data were also collected through usability surveys online post intervention and at the 3-month follow-up. Qualitative data were analysed with content analysis and quantitative data with descriptive statistics. The analysis of the interviews resulted in four categories describing the participants' experiences of the programme's usability and value: A valuable and flexible tool that requires time and discipline, New perspective and coping strategies for an enhanced well-being, I'm important too - my limits, my responsibility, and Taming the inner critic. The programme's usability was satisfactory and largely corroborated by the surveys. The programme was experienced as a valuable tool to cope with stress in both private and professional contexts, making it a viable option to support families living with mental health problems. Time for self-care, a widened perspective, a less judgmental and more accepting attitude, deterring automatic reactions and setting limits helped the participants to deal with their situation and health. The programme's ease and flexibility of use were major advantages, although the training requires discipline. Motivators and barriers to use were illuminated, which should be considered in the development of further online services and study designs. PMID- 27189238 TI - First-in-human robotic percutaneous coronary intervention for unprotected left main stenosis. AB - The safety and feasibility of robotically-assisted percutaneous coronary intervention (PCI) for simple coronary lesions has been demonstrated. The CorPath robotic system (Corpath 200, Corindus, Waltham, MA) consists of a robotic arm mounted on the cardiac catheterization table that consists of a drive housing a single-use sterile cassette, which is connected to the guiding catheter. While sitting in the nonsterile, radiation-shielded cockpit, the operator remotely controls delivery and removal of coronary guidewires, angioplasty balloons, and stents. The database for the ongoing PRECISION registry was queried at a single center and results of unprotected left main robotic PCI procedures are reported. Of 102 robotic PCI procedures performed at this center, 6 were unprotected left main lesions (age 69 +/- 14 years; 67% male). All 6 subjects underwent successful PCI (fluoroscopy time 26.8 +/- 11.4 min;1.8 stents and 2.2 vessels treated/patient) with three requiring hemodynamic support (two with percutaneous left ventricular assistance using the Impella 2.5 (Abiomed, Danvers, MA) and one with intraaortic balloon pump counterpulsation). This report demonstrates the feasibility of performing robotically assisted unprotected left main PCI with or without hemodynamic support. (c) 2016 Wiley Periodicals, Inc. PMID- 27189251 TI - Efficient artificial mineralization route to decontaminate Arsenic(III) polluted water - the Tooeleite Way. AB - Increasing exposure to arsenic (As) contaminated ground water is a great threat to humanity. Suitable technology for As immobilization and removal from water, especially for As(III) than As(V), is not available yet. However, it is known that As(III) is more toxic than As(V) and most groundwater aquifers, particularly the Gangetic basin in India, is alarmingly contaminated with it. In search of a viable solution here, we took a cue from the natural mineralization of Tooeleite, a mineral containing Fe(III) and As(III)ions, grown under acidic condition, in presence of SO4(2-) ions. Complying to this natural process, we could grow and separate Tooeleite-like templates from Fe(III) and As(III) containing water at overall circumneutral pH and in absence of SO4(2-) ions by using highly polar Zn only ends of wurtzite ZnS nanorods as insoluble nano-acidic-surfaces. The central idea here is to exploit these insoluble nano-acidic-surfaces (called as INAS in the manuscript) as nucleation centres for Tooeleite growth while keeping the overall pH of the aqueous media neutral. Therefore, we propose a novel method of artificial mineralization of As(III) by mimicking a natural process at nanoscale. PMID- 27189252 TI - [Acquired von-Willebrand factor and factor-VIII deficiencies caused by angiostrongylosis in a dog]. AB - An 8-year-old male Australian Shepherd was presented with bleeding from the lip and hemoabdomen. Hematology demonstrated marked thrombocytopenia and anemia. Abdominal ultrasound followed by laparotomy did not detect the cause of bleeding. Plasma transfusion resulted in temporary stabilization. Severe von-Willebrand factor deficiency and factor-VIII deficiency were diagnosed. After subsequent bleeding episodes, infection with Angiostrongylus vasorum was found in both a fecal parasitological examination and by PCR from EDTA-blood. Following successful therapy with fenbendazole, von Willebrand factor and factor VIII were within the normal range. This is the second case report of an acquired von Willebrand-factor deficiency associated with Angiostrongylus-vasorum infection in a dog, and the first case report with concurrent factor-VIII deficiency. PMID- 27189254 TI - A Hexakis Terpyridine-Fullerene Ligand in Six-Fold Ruthenium, Iridium, and Iron Complexes: Synthesis and Electrochemical Properties. AB - An unprecedented straightforward route to six-fold terpyridine ligands around C60 , the latter being regioselectively functionalized in pseudo-octahedral positions using a six-fold Bingel reaction, is reported. Ruthenium, iridium, and iron complexes have been synthesized, and unambiguously characterized by NMR, MS, and cyclic voltammetry. PMID- 27189253 TI - TRPA1 activation leads to neurogenic vasodilatation: involvement of reactive oxygen nitrogen species in addition to CGRP and NO. AB - BACKGROUND AND PURPOSE: Transient receptor potential ankyrin-1 (TRPA1) activation is known to mediate neurogenic vasodilatation. We investigated the mechanisms involved in TRPA1-mediated peripheral vasodilatation in vivo using the TRPA1 agonist cinnamaldehyde. EXPERIMENTAL APPROACH: Changes in vascular ear blood flow were measured in anaesthetized mice using laser Doppler flowmetry. KEY RESULTS: Topical application of cinnamaldehyde to the mouse ear caused a significant increase in blood flow in the skin of anaesthetized wild-type (WT) mice but not in TRPA1 knockout (KO) mice. Cinnamaldehyde-induced vasodilatation was inhibited by the pharmacological blockade of the potent microvascular vasodilator neuropeptide CGRP and neuronal NOS-derived NO pathways. Cinnamaldehyde-mediated vasodilatation was significantly reduced by treatment with reactive oxygen nitrogen species (RONS) scavenger such as catalase and the SOD mimetic TEMPOL, supporting a role of RONS in the downstream vasodilator TRPA1-mediated response. Co-treatment with a non-selective NOS inhibitor L-NAME and antioxidant apocynin further inhibited the TRPA1-mediated vasodilatation. Cinnamaldehyde treatment induced the generation of peroxynitrite that was blocked by the peroxynitrite scavenger FeTPPS and shown to be dependent on TRPA1, as reflected by an increase in protein tyrosine nitration in the skin of WT, but not in TRPA1 KO mice. CONCLUSION AND IMPLICATIONS: This study provides in vivo evidence that TRPA1 induced vasodilatation mediated by cinnamaldehyde requires neuronal NOS-derived NO, in addition to the traditional neuropeptide component. A novel role of peroxynitrite is revealed, which is generated downstream of TRPA1 activation by cinnamaldehyde. This mechanistic pathway underlying TRPA1-mediated vasodilatation may be important in understanding the role of TRPA1 in pathophysiological situations. PMID- 27189255 TI - Is daily exposure to ozone associated with respiratory morbidity and lung function in a representative sample of schoolchildren? Results from a panel study in Greece. AB - Previous time series or panel studies of asthmatics have reported respiratory health effects following short-term exposure to ozone (O3). We followed 186 children aged 10 years old in Athens and Thessaloniki, Greece for 5 weeks during the academic year 2013-2014 and recorded daily their respiratory symptoms, absenteeism and peak expiratory flow (PEF). We applied mixed models controlling for various possible confounders to investigate the daily associations between O3 exposure - derived from weekly personal and fixed school site measurements calibrated using daily values of the fixed monitoring site nearest to the child's school location - and PEF, presence of any symptom, cough and stuffy nose, as well as absenteeism. We tested the robustness of our findings to varying modeling assumptions and confounders and investigated effect modification patterns by medication use, time spent outdoors and prevalence of asthma. A 10 MUg/m3 increase in O3 personal exposure was associated with increased odds of any symptom (odds ratio (OR): 1.19, 95% confidence interval (CI): 0.98, 1.44), largely attributed to the increase in the odds of stuffy nose (OR: 1.23, 95% CI: 1.00, 1.51). PEF and absenteeism were not related to O3 exposure. Our results were robust to several sensitivity analyses. Effects were modified by medication use as presence of symptoms but also decreases in PEF were mainly reported among non-users, while our effect estimates were not driven by the asthmatic subgroup of children. Our findings indicate that short-term O3 exposure may be associated with respiratory symptoms extending previously reported results for asthmatics to the general population. PMID- 27189256 TI - Exposures to nanoparticles and fibers during injection molding and recycling of carbon nanotube reinforced polycarbonate composites. AB - In this study, the characteristics of airborne particles generated during injection molding and grinding processes of carbon nanotube reinforced polycarbonate composites (CNT-PC) were investigated. Particle number concentration, size distribution, and morphology of particles emitted from the processes were determined using real-time particle sizers and transmission electron microscopy. The air samples near the operator's breathing zone were collected on filters and analyzed using scanning electron microscope for particle morphology and respirable fiber count. Processing and grinding during recycling of CNT-PC released airborne nanoparticles (NPs) with a geometric mean (GM) particle concentration from 4.7 * 103 to 1.7 * 106 particles/cm3. The ratios of the GM particle concentration measured during the injection molding process with exhaust ventilation relative to background were up to 1.3 (loading), 1.9 (melting), and 1.4 (molding), and 101.4 for grinding process without exhaust ventilation, suggesting substantial NP exposures during these processes. The estimated mass concentration was in the range of 1.6-95.2 MUg/m3. Diverse particle morphologies, including NPs, NP agglomerates, particles with embedded or protruding CNTs and fibers, were observed. No free CNTs were found during any of the investigated processes. The breathing zone respirable fiber concentration during the grinding process ranged from non-detectable to 0.13 fiber/cm3. No evidence was found that the emissions were affected by the number of recycling cycles. Institution of exposure controls is recommended during these processes to limit exposures to airborne NPs and CNT-containing fibers. PMID- 27189258 TI - Prediction of fine particulate matter chemical components with a spatio-temporal model for the Multi-Ethnic Study of Atherosclerosis cohort. AB - Although cohort studies of the health effects of PM2.5 have developed exposure prediction models to represent spatial variability across participant residences, few models exist for PM2.5 components. We aimed to develop a city-specific spatio temporal prediction approach to estimate long-term average concentrations of four PM2.5 components including sulfur, silicon, and elemental and organic carbon for the Multi-Ethnic Study of Atherosclerosis cohort, and to compare predictions to those from a national spatial model. Using 2-week average measurements from a cohort-focused monitoring campaign, the spatio-temporal model employed selected geographic covariates in a universal kriging framework with the data-driven temporal trend. Relying on long-term means of daily measurements from regulatory monitoring networks, the national spatial model employed dimension-reduced predictors using universal kriging. For the spatio-temporal model, the cross validated and temporally-adjusted R(2) was relatively higher for EC and OC, and in the Los Angeles and Baltimore areas. The cross-validated R(2)s for both models across the six areas were reasonably high for all components except silicon. Predicted long-term concentrations at participant homes from the two models were generally highly correlated across cities but poorly correlated within cities. The spatio-temporal model may be preferred for city-specific health analyses, whereas both models could be used for multi-city studies. PMID- 27189259 TI - Severe combined immunodeficiencies and related disorders. AB - Severe combined immunodeficiencies (SCIDs) comprise a group of rare, monogenic diseases that are characterized by an early onset and a profound block in the development of T lymphocytes. Given that adaptive immunity is abrogated, patients with SCID are prone to recurrent infections caused by both non-opportunistic and opportunistic pathogens, leading to early death unless immunity can be restored. Several molecular defects causing SCIDs have been identified, along with many other defects causing profound, albeit incomplete, T cell immunodeficiencies; the latter are referred to as atypical SCIDs or combined immunodeficiencies. The pathophysiology of many of these conditions has now been characterized. Early, accurate and precise diagnosis combined with the ongoing implementation of newborn screening have enabled major advances in the care of infants with SCID, including better outcomes of allogeneic haematopoietic stem cell transplantation. Gene therapy is also becoming an effective option. Further advances and a progressive extension of the indications for gene therapy can be expected in the future. The assessment of long-term outcomes of patients with SCID is now a major challenge, with a view to evaluating the quality and sustainability of immune restoration, the risks of sequelae and the ability to relieve the non haematopoietic syndromic manifestations that accompany some of these conditions. PMID- 27189260 TI - Syncope: Not for the faint hearted. PMID- 27189261 TI - Synthetic polymers blend used in the production of high activated carbon for pesticides removals from liquid phase. AB - For the activated carbon (AC) production, we used the most common industrial and consumer solid waste, namely polyethyleneterephthalate (PET), alone or blended with other synthetic polymer such polyacrylonitrile (PAN). By mixing PET, with PAN, an improvement in the yield of the AC production was found and the basic character and some textural and chemical properties were enhanced. The PET-PAN mixture was subjected to carbonisation, with a pyrolysis yield of 31.9%, between that obtained with PET (16.9%) or PAN (42.6%) separately. The AC revealed a high surface area (1400, 1230 and 1117 m2 g-1) and pore volume (0.46, 0.56 and 0.50 cm3 g-1), respectively, for PET, PAN and PET-PAN precursors. Selected ACs were successfully tested for 4-chloro-2-methylphenoxyacetic acid (MCPA) and diuron removal from the liquid phase, showing a higher adsorption capacity (1.7 and 1.2 mmol g-1, respectively, for MCPA and diuron) and good fits with the Langmuir (PET) and Freundlich equation (PAN and PET-PAN blend). With MCPA, the controlling factor to the adsorption capacity was the porous volume and the average pore size. Concerning diuron, the adsorption was controlled essentially by the external diffusion. A remarkable result is the use of different synthetic polymers wastes, as precursors for the production of carbon materials, with high potential application on the pesticides removals from the liquid phase. PMID- 27189257 TI - Use of job-exposure matrices to estimate occupational exposure to pesticides: A review. AB - The health effects of pesticides have been extensively studied in epidemiology, mainly in agricultural populations. However, pesticide exposure assessment remains a key methodological issue for epidemiological studies. Besides self reported information, expert assessment or metrology, job-exposure matrices still appear to be an interesting tool. We reviewed all existing matrices assessing occupational exposure to pesticides in epidemiological studies and described the exposure parameters they included. We identified two types of matrices, (i) generic ones that are generally used in case-control studies and document broad categories of pesticides in a large range of jobs, and (ii) specific matrices, developed for use in agricultural cohorts, that generally provide exposure metrics at the active ingredient level. The various applications of these matrices in epidemiological studies have proven that they are valuable tools to assess pesticide exposure. Specific matrices are particularly promising for use in agricultural cohorts. However, results obtained with matrices have rarely been compared with those obtained with other tools. In addition, the external validity of the given estimates has not been adequately discussed. Yet, matrices would help in reducing misclassification and in quantifying cumulated exposures, to improve knowledge about the chronic health effects of pesticides. PMID- 27189262 TI - 3-Hydroxypropionic acid production by recombinant Escherichia coli ZJU-3HP01 using glycerol-glucose dual-substrate fermentative strategy. AB - 3-Hydroxypropionic acid (3-HP) is an important platform synthesis block for sets of chemicals, but the relatively low production of 3-HP from biological sources presented major barriers for its industrial applications. In this study, a dual substrate fermentative strategy by glycerol and glucose was proposed, and the aim was to evaluate the effect of different substrate addition strategies on the fermentation process. The results indicated that the optimal cosubstrate was glucose (20 g/L), and the enzymatic activity of aldehyde dehydrogenase (AldH) could be improved 3.5-fold as compared with no glucose addition. Continuous fed batch fermentation at a constant speed displayed better 3-HP production of 17.20 g/L and highest specific 3-HP productivity of 1.79 mmol/(g cell.H) than the other fed-batch mode. The addition of glucose could greatly reduce the imbalance of the activity between glycerol dehydratase and AldH and provide a feasible method for improving 3-HP production. These results would be helpful in developing the 3-HP fermentation process. PMID- 27189263 TI - Diverse anisotropy of phonon transport in two-dimensional group IV-VI compounds: A comparative study. AB - New classes of two-dimensional (2D) materials beyond graphene, including layered and non-layered, and their heterostructures, are currently attracting increasing interest due to their promising applications in nanoelectronics, optoelectronics and clean energy, where thermal transport is a fundamental physical parameter. In this paper, we systematically investigated the phonon transport properties of the 2D orthorhombic group IV-VI compounds of GeS, GeSe, SnS and SnSe by solving the Boltzmann transport equation (BTE) based on first-principles calculations. Despite their similar puckered (hinge-like) structure along the armchair direction as phosphorene, the four monolayer compounds possess diverse anisotropic properties in many aspects, such as phonon group velocity, Young's modulus and lattice thermal conductivity (kappa), etc. Especially, the kappa along the zigzag and armchair directions of monolayer GeS shows the strongest anisotropy while monolayer SnS and SnSe show almost isotropy in phonon transport. The origin of the diverse anisotropy is fully studied and the underlying mechanism is discussed in details. With limited size, the kappa could be effectively lowered, and the anisotropy could be effectively modulated by nanostructuring, which would extend the applications to nanoscale thermoelectrics and thermal management. Our study offers fundamental understanding of the anisotropic phonon transport properties of 2D materials, and would be of significance for further study, modulation and applications in emerging technologies. PMID- 27189264 TI - Neonatal screening for Menkes disease using urine HVA/VMA ratio. PMID- 27189266 TI - Solvation structure around the Li(+) ion in succinonitrile-lithium salt plastic crystalline electrolytes. AB - Herein, we discuss the study of solvation dynamics of lithium-succinonitrile (SN) plastic crystalline electrolytes by ultrafast vibrational spectroscopy. The infrared absorption spectra indicated that the CN stretch of the Li(+) bound and unbound succinonitrile molecules in a same solution have distinct vibrational frequencies (2276 cm(-1)vs. 2253 cm(-1)). The frequency difference allowed us to measure the rotation decay times of solvent molecules bound and unbound to Li(+) ion. The Li(+) coordination number of the Li(+)-SN complex was found to be 2 in the plastic crystal phase (22 degrees C) and 2.5-3 in the liquid phase (80 degrees C), which is independent of the concentration (from 0.05 mol kg(-1) to 2 mol kg(-1)). The solvation structures along with DFT calculations of the Li(+)-SN complex have been discussed. In addition, the dissociation percentage of lithium salt was also determined. In 0.5 mol kg(-1) LiBF4-SN solutions at 80 degrees C, 60% +/- 10% of the salt dissociates into Li(+), which is bound by 2 or 3 solvent molecules. In the 0.5 mol kg(-1) LiClO4-SN solutions at 80 degrees C, the salt dissociation ratio can be up to 90% +/- 10%. PMID- 27189265 TI - Attention-deficit/hyperactivity disorder. AB - Attention-deficit/hyperactivity disorder (ADHD) is a persistent neurodevelopmental disorder that affects 5% of children and adolescents and 2.5% of adults worldwide. Throughout an individual's lifetime, ADHD can increase the risk of other psychiatric disorders, educational and occupational failure, accidents, criminality, social disability and addictions. No single risk factor is necessary or sufficient to cause ADHD. In most cases ADHD arises from several genetic and environmental risk factors that each have a small individual effect and act together to increase susceptibility. The multifactorial causation of ADHD is consistent with the heterogeneity of the disorder, which is shown by its extensive psychiatric co-morbidity, its multiple domains of neurocognitive impairment and the wide range of structural and functional brain anomalies associated with it. The diagnosis of ADHD is reliable and valid when evaluated with standard criteria for psychiatric disorders. Rating scales and clinical interviews facilitate diagnosis and aid screening. The expression of symptoms varies as a function of patient developmental stage and social and academic contexts. Although there are no curative treatments for ADHD, evidenced-based treatments can markedly reduce its symptoms and associated impairments. For example, medications are efficacious and normally well tolerated, and various non pharmacological approaches are also valuable. Ongoing clinical and neurobiological research holds the promise of advancing diagnostic and therapeutic approaches to ADHD. For an illustrated summary of this Primer, visit: http://go.nature.com/J6jiwl. PMID- 27189267 TI - Heat Shock Factor 1 Mediates Latent HIV Reactivation. AB - HSF1, a conserved heat shock factor, has emerged as a key regulator of mammalian transcription in response to cellular metabolic status and stress. To our knowledge, it is not known whether HSF1 regulates viral transcription, particularly HIV-1 and its latent form. Here we reveal that HSF1 extensively participates in HIV transcription and is critical for HIV latent reactivation. Mode of action studies demonstrated that HSF1 binds to the HIV 5'-LTR to reactivate viral transcription and recruits a family of closely related multi subunit complexes, including p300 and p-TEFb. And HSF1 recruits p300 for self acetylation is also a committed step. The knockout of HSF1 impaired HIV transcription, whereas the conditional over-expression of HSF1 improved that. These findings demonstrate that HSF1 positively regulates the transcription of latent HIV, suggesting that it might be an important target for different therapeutic strategies aimed at a cure for HIV/AIDS. PMID- 27189268 TI - The pattern of anxiolytic and hypnotic management by Australian general practice trainees. AB - INTRODUCTION AND AIMS: Guidelines recommend anxiolytics and hypnotics (A/H) as second-line, short-term medications. We aimed to establish prevalence and associations of A/H prescribing by Australian general practice (GP) trainees. DESIGN AND METHODS: A cross-sectional analysis from a cohort study of vocational trainees from four GP Regional Training Providers during 2010-2013. General practice trainees act as independent practitioners (including for prescribing purposes) while having recourse to advice from a GP supervisor. Practice and trainee demographic data were collected as well as patient, clinical and educational data from 60 consecutive consultations of each trainee each training term. Analysis was at the level of individual problem managed, with the outcome factor being prescription of any anxiolytic or hypnotic. RESULTS: Overall, 645 registrars (response rate 94.0%) prescribed 68 582 medications in 69 621 consultations (with 112 890 problems managed). A/Hs were prescribed for 1.3% of problems managed and comprised 2.2% of all prescriptions. They were prescribed particularly for insomnia (28.2%) or anxiety (21.8%), but also for many 'off label' indications. Significant associations of A/H prescriptions were: patient level (greater age, Aboriginal and Torres Strait Islander status, English speaking background, being new to the trainee but not to the practice); trainee level (male) and consultation-level (longer duration, pre-existing problem, specialist referral not being made). Prescribing was significantly lower in one of the four Regional Training Providers. DISCUSSION AND CONCLUSIONS: GP trainees, inconsistent with most guideline recommendations, prescribe A/Hs mainly as maintenance therapy to unfamiliar and older patients. Our results suggest that changes in management approaches are needed which may be facilitated by support for psychotherapeutic training. [Holliday SM, Morgan S, Tapley A, Henderson KM, Dunlop AJ, van Driel ML, Spike NA, McArthur LA, Ball J, Oldmeadow CJ, Magin PJ. The pattern of anxiolytic and hypnotic management by Australian general practice trainees. Drug Alcohol Rev 2017;36:261-269]. PMID- 27189269 TI - Commercial processed soy-based food product contains glycated and glycoxidated lunasin proteoforms. AB - Nutraceuticals have been proposed to exert positive effects on human health and confer protection against many chronic diseases. A major bioactive component of soy-based foods is lunasin peptide, which has potential to exert a major impact on the health of human consumers worldwide, but the biochemical features of dietary lunasin still remain poorly characterized. In this study, lunasin was purified from a soy-based food product via strong anion exchange solid phase extraction and then subjected to top-down mass spectrometry analysis that revealed in detail the molecular diversity of lunasin in processed soybean foods. We detected multiple glycated proteoforms together with potentially toxic advanced glycation end products (AGEs) derived from lunasin. In both cases, modification sites were Lys24 and Lys29 located at the helical region that shows structural homology with a conserved region of chromatin-binding proteins. The identified post-translational modifications may have an important repercussion on lunasin epigenetic regulatory capacity. Taking together, our results demonstrate the importance of proper chemical characterization of commercial processed food products to assess their impact on consumer's health and risk of chronic diseases. PMID- 27189270 TI - The molecular phylogeny of the digenean family Opecoelidae Ozaki, 1925 and the value of morphological characters, with the erection of a new subfamily. AB - Large and small rDNA sequences of 41 species of the family Opecoelidae are utilised to produce phylogenetic inference trees, using brachycladioids and lepocreadioids as outgroups. Sequences were newly generated for 13 species. The resulting Bayesian trees show a monophyletic Opecoelidae. The earliest divergent group is the Stenakrinae, based on two species which are not of the type-genus. The next well-supported clade to diverge is constituted of three species of Helicometra Odhner, 1902. Based on this tree and the characters of the egg and uterus, a new subfamily, the Helicometrinae, is erected and defined to include the genera Helicometra, Helicometrina Linton, 1910 and Neohelicometra Siddiqi et Cable, 1960. The subfamily Opecoelinae is found to be monophyletic, but the Plagioporinae is paraphyletic. The single representative of the Opecoelininae (not of the type genus) is nested within a group of deep-sea 'plagioporines'. The two representatives of the Opistholebetidae are embedded within a group of shallow-water 'plagioporine' species. The Opistholebetidae is reduced to subfamily status pro tem as its morphological and biological characteristics are distinctive. This implies that as opecoelid systematics develops with more molecular evidence, several further subfamilies will be recognised. Many of the morphological characters were found to be homoplasious, but the characters defining the Helicometrinae and Opecoelinae, such as filamented eggs, reduced cirrus-sac and uterine seminal receptacle, are closely correlated with the inferred phylogeny. PMID- 27189271 TI - In Hot Pursuit of the First Vaccine Against Respiratory Syncytial Virus. AB - Human respiratory syncytial virus (RSV) is the leading cause of severe lower respiratory tract infection, such as bronchiolitis, bronchitis, or pneumonia, in both infants and the elderly. Despite the global burden of diseases attributable to RSV infection, no clinically approved vaccine is available, and a humanized monoclonal antibody for prophylaxis is not readily affordable in developing countries. There are several hurdles to the successful development of RSV vaccines: immune-vulnerable target populations such as premature infants, pregnant women, and immunocompromised people; safety concerns associated with vaccine-enhanced diseases; repeated infection; and waning memory. To develop successful strategies for the prevention of RSV infection, it is necessary to understand the protective and pathologic roles of host immune responses to RSV infection. In this review, we will summarize the positive and negative relationship between RSV infection and host immunity and discuss strategies for the development of the first successful RSV vaccine. PMID- 27189272 TI - Hearing Restoration in Neurofibromatosis Type II Patients. AB - Patients with neurofibromatosis type II will eventually succumb to bilateral deafness. For patients with hearing loss, modern medical science technology can provide efficient hearing restoration through a number of various methods. In this article, several hearing restoration methods for patients with neurofibromatosis type II are introduced. PMID- 27189274 TI - Fibroblast Growth Factor Receptor 1 Overexpression Is Associated with Poor Survival in Patients with Resected Muscle Invasive Urothelial Carcinoma. AB - PURPOSE: To examine the usefulness of various receptor tyrosine kinase expressions as prognostic markers and therapeutic targets in muscle invasive urothelial cancer (UC) patients. MATERIALS AND METHODS: We retrospectively analyzed the data of 98 patients with muscle invasive UC who underwent radical cystectomy between 2005 and 2010 in Yonsei Cancer Center. Using formalin fixed paraffin embedded tissues of primary tumors, immunohistochemical staining was done for human epidermal growth factor receptor 2 (HER2), fibroblast growth factor receptor 1 (FGFR1), and fibroblast growth factor receptor 3 (FGFR3). RESULTS: There were 41 (41.8%), 44 (44.9%), and 14 (14.2%) patients who have over expressed HER2, FGFR1, and FGFR3, respectively. In univariate analysis, significantly shorter median time to recurrence (TTR) (12.9 months vs. 49.0 months; p=0.008) and overall survival (OS) (22.3 months vs. 52.7 months; p=0.006) was found in patients with FGFR1 overexpression. By contrast, there was no difference in TTR or OS according to the HER2 and FGFR3 expression status. FGFR1 remained as a significant prognostic factor for OS with hazard ratio of 2.23 (95% confidence interval: 1.27-3.90, p=0.006) in multivariate analysis. CONCLUSION: Our result showed that FGFR1 expression, but not FGFR3, is an adverse prognostic factor in muscle invasive UC patients after radical cystectomy. FGFR1 might be feasible for prognosis prediction and a potential therapeutic target after thorough validation in muscle invasive UC. PMID- 27189273 TI - Re-Irradiation for Recurrent Gliomas: Treatment Outcomes and Prognostic Factors. AB - PURPOSE: The aim of this study was to evaluate the efficacy of re-irradiation in patients with recurrent gliomas and to identify subgroups for whom re-irradiation for recurrent gliomas is most beneficial. MATERIALS AND METHODS: We retrospectively reviewed 36 patients with recurrent or progressive gliomas who received re-irradiation between January 1996 and December 2011. Re-irradiation was offered to recurrent glioma patients with good performance or at least 6 months had passed after initial radiotherapy (RT), with few exceptions. RESULTS: Median doses of re-irradiation and initial RT were 45.0 Gy and 59.4 Gy, respectively. The median time interval between initial RT and re-irradiation was 30.5 months. Median overall survival (OS) and the 12-month OS rate were 11 months and 41.7%, respectively. In univariate analysis, Karnofsky performance status (KPS) >=70 (p<0.001), re-irradiation dose >=45 Gy (p=0.040), and longer time interval between initial RT and re-irradiation (p=0.040) were associated with improved OS. In multivariate analysis, KPS (p=0.030) and length of time interval between initial RT and re-irradiation (p=0.048) were important predictors of OS. A radiographically suspected mixture of radiation necrosis and progression after re-irradiation was seen in 5 patients. CONCLUSION: Re-irradiation in conjunction with surgery could be a salvage treatment for selected recurrent glioma patients with good performance status and recurrence over a long time. PMID- 27189275 TI - Prognostic Evaluation of Nasopharyngeal Carcinoma with Bone-Only Metastasis after Therapy. AB - PURPOSE: To evaluate the prognosis of nasopharyngeal carcinoma (NPC) patients who developed bone-only metastasis after primary treatment and the stratification of these patients into different risk groups based on independent prognostic factors. MATERIALS AND METHODS: Eighty NPC patients who developed bone-only metastasis after definitive radiotherapy from October 2005 to December 2010 were enrolled. All these patients received palliative treatment for bone metastasis, including chemotherapy and/or radiotherapy. Clinical features, treatment modality, and laboratory parameters were examined with univariate and multivariate analyses. RESULTS: The median follow-up time was 15.5 months (range, 2-67 months) for the whole cohort. The median overall metastatic survival (OMS) time and the 2-year estimate OMS rate were 26.5 months and 52%, respectively. Multivariate analysis indicated that patients with short metastases-free interval, multiple bone metastases sites, high serum lactic dehydrogenase levels, and treated with radiotherapy or chemotherapy alone had significantly worse outcomes. Patients were stratified into three different risk groups based on the number of adverse factors present. The OMS curves of the three groups were all significantly different (p<0.001). CONCLUSION: Severl prognostic factors were found to be associated with worse outcomes. According to the number of adverse factors present, bone-only metastasis patients can be stratified into three risk groups with significantly different prognoses. Such grouping may help in improving the design of clinical trials and in guiding individualized treatment for NPC patients with bone-only metastasis. PMID- 27189276 TI - The Roles of Radiotherapy and Chemotherapy in the Era of Multimodal Treatment for Early-Stage Nasal-Type Extranodal Natural Killer/T-Cell Lymphoma. AB - PURPOSE: To evaluate radiotherapy (RT) and chemotherapy (CT) treatments of early stage extranodal natural killer/T-cell lymphoma (ENKTL). MATERIALS AND METHODS: Fifty-five patients with stage I or II ENKTL [n=39 (71%) and 16 (29%) patients, respectively] who were treated with RT between 1999 and 2013 were analyzed retrospectively. The median age was 54 years (range, 24-81). Patients were grouped by treatment modality as RT alone [n=19 (35%)], upfront CT plus RT [CT+RT, n=16 (29%)], and concurrent chemoradiotherapy [CCRT, n=20 (36%)]. The median RT dose was 48 Gy. Patient characteristics between each treatment group were well balanced. Patterns of failure and survival were analyzed. RESULTS: The overall response rate after RT was 94.6%. Ten patients experienced distant failure, and seven experienced local failure comprising five in-field and two out field failures. The local and distant failure rates in the RT-alone group were the same (16%). In the CT+RT group, the most common failure sites were local (19%). In the CCRT group, the most common failures were distant (25%). At a median follow-up of 56 months (range, 1-178 months), the 5-year overall survival (OS) and progression-free survival rates were 66% and 54%, respectively. The 5 year OS rate for the RT-alone and CT+RT groups were 76% and 69%, respectively, and the 2-year OS rate for the CCRT group was 62% (p=0.388). CONCLUSION: In the era of multimodal treatment for ENKTL, RT alone using advanced techniques should be considered for local disease control, whereas maintenance CT regimens should be considered for distant disease control. PMID- 27189277 TI - Prognostic Factors for Recurrence and Progression in Korean Non-Muscle-Invasive Bladder Cancer Patients: A Retrospective, Multi-Institutional Study. AB - PURPOSE: To identify the prognostic factors related to tumor recurrence and progression in Korean patients with non-muscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS: Data were collected and analyzed for 2412 NMIBC patients from 15 centers who were initially diagnosed after transurethral resection of bladder tumor (TURBT) from January 2006 to December 2010. Using univariable and multivariable Cox proportional hazards models, the prognostic value of each variable was evaluated for the time to first recurrence and progression. RESULTS: With a median follow-up duration of 37 months, 866 patients (35.9%) experienced recurrence, and 137 (5.7%) experienced progression. Patients with recurrence had a median time to the first recurrence of 10 months. Multivariable analysis conducted in all patients revealed that preoperative positive urine cytology (PUC) was independently associated with worse recurrence-free survival [RFS; hazard ratio (HR) 1.56; p<0.001], and progression-free survival (PFS; HR 1.56; p=0.037). In particular, on multivariable analysis conducted for the high-risk group (T1 tumor/high-grade Ta tumor/carcinoma in situ), preoperative PUC was an independent predictor of worse RFS (HR 1.73; p<0.001) and PFS (HR 1.96; p=0.006). On multivariable analysis in patients with T1 high-grade (T1HG) cancer (n=684), better RFS (HR 0.75; p=0.033) and PFS (HR 0.33; p<0.001) were observed in association with the administration of intravesical Bacillus Calmette-Guerin (BCG) induction therapy. CONCLUSION: A preoperative PUC result may adversely affect RFS and PFS, particularly in high-risk NMIBC patients. Of particular note, intravesical BCG induction therapy should be administered as an adjunct to TURBT in order to improve RFS and PFS in patients with T1HG cancer. PMID- 27189279 TI - Estimation of Prognostic Marker Genes by Public Microarray Data in Patients with Ovarian Serous Cystadenocarcinoma. AB - PURPOSE: Lymphatic invasion (LI) is regarded as a predictor of the aggressiveness of ovarian cancer (OC). However, LI is not always the major determinant of long term patient survival. To establish proper diagnosis and treatment for OC, we analyzed differentially expressed genes (DEGs) for patients with serous epithelial OC, with or without LI, who did or did not survive for 5 years. MATERIALS AND METHODS: Gene expression data from 63 patients with OC and LI, and 35 patients with OC but without LI, were investigated using an Affymetrix Human Genome U133 Array and analyzed using The Cancer Genome Atlas (TCGA) database. Among these 98 patients, 16 survived for 5 years or more. DEGs were identified using the Bioconductor R package, and their functions were analyzed using the DAVID web tool. RESULTS: We found 55 significant DEGs (p<0.01) from the patients with LI and 20 highly significant DEGs (p<0.001) from those without it. Pathway analysis showed that DEGs associated with carbohydrate metabolism or with renal cell carcinoma pathways were enriched in the patients with and without LI, respectively. Using the top five prognostic marker genes, we generated survival scores that could be used to predict the 5-year survival of patients with OC without LI. CONCLUSION: The DEGs identified in this study could be used to elucidate the mechanism of tumor progression and to guide the prognosis and treatment of patients with serous OC but without LI. PMID- 27189280 TI - Aldehyde Dehydrogenase 2 (ALDH2) Polymorphism and the Risk of Alcoholic Liver Cirrhosis among East Asians: A Meta-Analysis. AB - PURPOSE: The aldehyde dehydrogenase 2 (ALDH2) gene has been implicated in the development of alcoholic liver cirrhosis (ALC) in East Asians. However, the results are inconsistent. In this study, a meta-analysis was performed to assess the associations between the ALDH2 polymorphism and the risk of ALC. MATERIALS AND METHODS: Relevant studies were retrieved by searching PubMed, Web of Science, CNKI, Wanfang and Veipu databases up to January 10, 2015. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using either the fixed- or random effects model. RESULTS: A total of twelve case-control studies included 1003 cases and 2011 controls were included. Overall, the ALDH2 polymorphism was associated with a decreased risk of ALC (*1/*2 vs. *1/*1: OR=0.78, 95% CI: 0.61 0.99). However, in stratification analysis by country, we failed to detect any association among Chinese, Korean or Japanese populations. CONCLUSION: The pooled evidence suggests that ALDH2 polymorphism may be an important protective factor for ALC in East Asians. PMID- 27189278 TI - Metabolic Pathway Signatures Associated with Urinary Metabolite Biomarkers Differentiate Bladder Cancer Patients from Healthy Controls. AB - PURPOSE: Our previous high-performance liquid chromatography-quadrupole time-of flight mass spectrometry study identified bladder cancer (BCA)-specific urine metabolites, including carnitine, acylcarnitines, and melatonin. The objective of the current study was to determine which metabolic pathways are perturbed in BCA, based on our previously identified urinary metabolome. MATERIALS AND METHODS: A total of 135 primary BCA samples and 26 control tissue samples from healthy volunteers were analyzed. The association between specific urinary metabolites and their related encoding genes was analyzed. RESULTS: Significant alterations in the carnitine-acylcarnitine and tryptophan metabolic pathways were detected in urine specimens from BCA patients compared to those of healthy controls. The expression of eight genes involved in the carnitine-acylcarnitine metabolic pathway (CPT1A, CPT1B, CPT1C, CPT2, SLC25A20, and CRAT) or tryptophan metabolism (TPH1 and IDO1) was assessed by RT-PCR in our BCA cohort (n=135). CPT1B, CPT1C, SLC25A20, CRAT, TPH1, and IOD1 were significantly downregulated in tumor tissues compared to normal bladder tissues (p<0.05 all) of patients with non-muscle invasive BCA, whereas CPT1B, CPT1C, CRAT, and TPH1 were downregulated in those with muscle invasive BCA (p<0.05), with no changes in IDO1 expression. CONCLUSION: Alterations in the expression of genes associated with the carnitine acylcarnitine and tryptophan metabolic pathways, which were the most perturbed pathways in BCA, were determined. PMID- 27189282 TI - Cyclooxygenase-2 Inhibitor Reduces Hepatic Stiffness in Pediatric Chronic Liver Disease Patients Following Kasai Portoenterostomy. AB - PURPOSE: The purpose of this study was to define the role of cyclooxygenase-2 inhibitors (COX-2i) in reducing hepatic fibrosis in pediatric patients with chronic liver disease. MATERIALS AND METHODS: From September 2009 to September 2010, patients over 2 years old who visited our outpatient clinic for follow-up to manage their chronic liver disease after Kasai portoenterostomy for biliary atresia, were included in this study. Volunteers were assigned to the study or control groups, according to their preference. A COX-2i was given to only the study group after obtaining consent. The degree of hepatic fibrosis (liver stiffness score, LSS) was prospectively measured using FibroScan, and liver function was examined using serum analysis before and after treatment. After 1 year, changes in LSSs and liver function were compared between the two groups. RESULTS: Twenty-five patients (18 females and 7 males) were enrolled in the study group. The control group included 44 patients (26 females and 18 males). After 1 year, the least square mean values for the LSSs were significantly decreased by 3.91+/-0.98 kPa (p=0.004) only in the study group. Serum total bilirubin did not decrease significantly in either group. CONCLUSION: COX-2i treatment improved the LSS in patients with chronic liver disease after Kasai portoenterostomy for biliary atresia. PMID- 27189281 TI - The Relationship between Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease Measured by Controlled Attenuation Parameter. AB - PURPOSE: The severity of non-alcoholic fatty liver disease (NAFLD) in type 2 diabetes mellitus (T2DM) population compared with that in normal glucose tolerance (NGT) individuals has not yet been quantitatively assessed. We investigated the prevalence and the severity of NAFLD in a T2DM population using controlled attenuation parameter (CAP). MATERIALS AND METHODS: Subjects who underwent testing for biomarkers related to T2DM and CAP using Fibroscan(r) during a regular health check-up were enrolled. CAP values of 250 dB/m and 300 dB/m were selected as the cutoffs for the presence of NAFLD and for moderate to severe NAFLD, respectively. Biomarkers related to T2DM included fasting glucose/insulin, fasting C-peptide, hemoglobin A1c (HbA1c), glycoalbumin, and homeostasis model assessment of insulin resistance of insulin resistance (HOMA IR). RESULTS: Among 340 study participants (T2DM, n=66; pre-diabetes, n=202; NGT, n=72), the proportion of subjects with NAFLD increased according to the glucose tolerance status (31.9% in NGT; 47.0% in pre-diabetes; 57.6% in T2DM). The median CAP value was significantly higher in subjects with T2DM (265 dB/m) than in those with pre-diabetes (245 dB/m) or NGT (231 dB/m) (all p<0.05). Logistic regression analysis showed that subjects with moderate to severe NAFLD had a 2.8-fold (odds ratio) higher risk of having T2DM than those without NAFLD (p=0.02; 95% confidence interval, 1.21-6.64), and positive correlations between the CAP value and HOMA-IR (rho0.407) or fasting C-peptide (rho0.402) were demonstrated. CONCLUSION: Subjects with T2DM had a higher prevalence of severe NAFLD than those with NGT. Increased hepatic steatosis was significantly associated with the presence of T2DM, and insulin resistance induced by hepatic fat may be an important mechanistic connection. PMID- 27189283 TI - Early Marker of Myocardial Deformation in Children with Duchenne Muscular Dystrophy Assessed Using Echocardiographic Myocardial Strain Analysis. AB - PURPOSE: As cardiomyopathy is more prevalent and currently the leading cause of death in Duchenne muscular dystrophy (DMD), early detection of myocardial involvement is important. The purpose of this study was to analyze myocardial strain in DMD children, for the possibility of early detection of myocardial dysfunction. MATERIALS AND METHODS: We reviewed medical records of DMD patients who were >10 years of age (15.6+/-1.6 years, 12.5-18 years), from March 2013 to June 2014. Data of 24 DMD children who underwent echocardiography with three layer specific myocardial strain were compared with 24 controls (age: 9.3+/-4.0 years, 5.5-17 years). RESULTS: Epicardial longitudinal strain was lower in DMD (DMD: -9.3+/-3.8%; control: -12.3+/-4.3%; p=0.012). Radial strain (DMD: 24.1+/ 11.1%; control: 37.3+/-25.9%; p=0.027) and strain rate (SR) (DMD: 1.68+/-0.91; control: 2.42+/-0.84; p=0.006) on parasternal short axis view were lower in DMD. Circumferential strains in the endocardium (DMD: -17.5+/-4.7%; control: -24.2+/ 5.3%; p<0.001), myocardium (DMD: -12.7+/-3.8%; control: -18.0+/-4.0%; p<0.001), and epicardium (DMD: -8.4+/-4.0%; control: -12.2+/-5.0%; p=0.006) were significantly decreased in DMD. Circumferential SRs were lower in the endocardial (DMD: -1.46+/-0.38; control: -1.78+/-0.27; p=0.002) and myocardial layers (DMD: 1.02+/-0.27; control: -1.28+/-0.22; p=0.001). CONCLUSION: In DMD patients, deteriorations in myocardial circumferential strain might be an indicator for predicting cardiomyopathy. PMID- 27189285 TI - Subclinical Hypothyroidism in Childhood Cancer Survivors. AB - PURPOSE: In childhood cancer survivors, the most common late effect is thyroid dysfunction, most notably subclinical hypothyroidism (SCH). Our study evaluated the risk factors for persistent SCH in survivors. MATERIALS AND METHODS: Survivors (n=423) were defined as patients who survived at least 2 years after cancer treatment completion. Thyroid function was assessed at this time and several years thereafter. Two groups of survivors with SCH were compared: those who regained normal thyroid function during the follow-up period (normalized group) and those who did not (persistent group). RESULTS: Overall, 104 of the 423 survivors had SCH. SCH was observed in 26% of brain or nasopharyngeal cancer survivors (11 of 43) and 21.6% of leukemia survivors (35 of 162). Sixty-two survivors regained normal thyroid function, 30 remained as persistent SCH, and 12 were lost to follow-up. The follow-up duration was 4.03 (2.15-5.78) years. Brain or nasopharyngeal cancer and Hodgkin disease were more common in the persistent group than in the normalized group (p=0.002). More patients in the persistent group received radiation (p=0.008). Radiation to the head region was higher in this group (2394+/-2469 cGy) than in the normalized group (894+/-1591 cGy; p=0.003). On multivariable analysis, lymphoma (p=0.011), brain or nasopharyngeal cancer (p=0.039), and head radiation dose >=1800 cGy (p=0.039) were significant risk factors for persistent SCH. CONCLUSION: SCH was common in childhood cancer survivors. Brain or nasopharyngeal cancer, lymphoma, and head radiation >=1800 cGy were significant risk factors for persistent SCH. PMID- 27189284 TI - Assessment of Denosumab in Korean Postmenopausal Women with Osteoporosis: Randomized, Double-Blind, Placebo-Controlled Trial with Open-Label Extension. AB - PURPOSE: The efficacy and safety of denosumab was compared with placebo in Korean postmenopausal women with osteoporosis in this phase III study. MATERIALS AND METHODS: Women aged 60 to 90 years with a T-score of <-2.5 and >=-4.0 at the lumbar spine or total hip were randomized to a single 60 mg subcutaneous dose of denosumab or placebo for the 6-month double-blind phase. Eligible subjects entered the 6-month open-label extension phase and received a single dose of denosumab 60 mg. RESULTS: Baseline demographics were similar in the 62 denosumab- and 64 placebo-treated subjects who completed the double-blind phase. Treatment favored denosumab over placebo for the primary endpoint {mean percent change from baseline in lumbar spine bone mineral density (BMD) at Month 6 [3.2% (95% confidence interval 2.1%, 4.4%; p<0.0001)]}; and secondary endpoints (mean percent change from baseline in lumbar spine BMD at Month 1, total hip, femoral neck, and trochanter BMD at Months 1 and 6, and median percent change from baseline in bone turnover markers at Months 1, 3, and 6). Endpoint improvements were sustained over 12 months in the open-label extension (n=119). There were no new or unexpected safety signals. CONCLUSION: Denosumab was well tolerated and effective in increasing BMD and decreasing bone turnover markers over a 12-month period in Korean postmenopausal women. The findings of this study demonstrate that denosumab has beneficial effects on the measures of osteoporosis in Korean postmenopausal women. PMID- 27189287 TI - Efficacy and Safety of Roflumilast in Korean Patients with COPD. AB - PURPOSE: Roflumilast is the only oral phosphodiesterase 4 inhibitor approved to treat chronic obstructive pulmonary disease (COPD) patients [post-bronchodilator forced expiratory volume in 1 second (FEV1) <50% predicted] with chronic bronchitis and a history of frequent exacerbations. This study evaluated the efficacy and safety of roflumilast in Korean patients with COPD and compared the efficacy based on the severity of airflow limitation. MATERIALS AND METHODS: A post-hoc subgroup analysis was performed in Korean COPD patients participating in JADE, a 12-week, double-blinded, placebo-controlled, parallel-group, phase III trial in Asia. The primary efficacy endpoint was the mean [least-squares mean adjusted for covariates (LSMean)] change in post-bronchodilator FEV1 from baseline to each post-randomization visit. Safety endpoints included adverse events (AEs) and changes in laboratory values, vital signs, and electrocardiograms. RESULTS: A total of 260 Korean COPD patients were recruited, of which 207 were randomized to roflumilast (n=102) or placebo (n=105) treatment. After 12 weeks, LSMean post-bronchodilator FEV1 increased by 43 mL for patients receiving roflumilast and decreased by 60 mL for those taking placebo. Adverse events were more common in the roflumilast group than in the placebo group; however, the types and frequency of AEs were comparable to those reported in previous studies. CONCLUSION: Roflumilast significantly improved lung function with a tolerable safety profile in Korean COPD patients irrespective of the severity of airflow limitation. PMID- 27189286 TI - Vitamin D Repletion in Korean Postmenopausal Women with Osteoporosis. AB - PURPOSE: Up to 71% of South Korean postmenopausal women have vitamin D deficiency {serum 25-hydroxyvitamin D [25(OH) D] level <50 nmol/L}. Data on vitamin D supplementation was collected during the screening phase of an efficacy/safety study of denosumab in Korean postmenopausal women with osteoporosis. This report describes the effect of vitamin D supplementation on repletion to 25(OH)D levels >=50 nmol/L in Korean postmenopausal women with osteoporosis. MATERIALS AND METHODS: Vitamin D levels of Korean postmenopausal women (60-90 years old) were measured by extracting 25(OH)D2 and 25(OH)D3 from serum samples via protein precipitation and using liquid chromatography with tandem mass spectrometry detection. Calibration curves were constructed from the mass chromatograms to obtain total vitamin D levels. Subjects with serum 25(OH)D levels <50 nmol/L were supplemented with 1000 IU of vitamin D tablets during the 2.5-month-long screening period. Dose, frequency, and duration were determined by the investigator. If repletion was achieved (>=50 nmol/L) on retest, subjects were eligible to be rescreened for study entry. RESULTS: Of 371 subjects screened, 191 (52%) required vitamin D supplementation, and 88% (168 of 191) were successfully repleted. More than half of the subjects (58%) who were successfully repleted received doses of 2000 IU daily. The mean time to successful repletion was 31 days (standard deviation 8.4 days; range 11-48 days). CONCLUSION: Supplementation with daily median doses of 2000 IU vitamin D successfully repleted 88% of Korean postmenopausal women with osteoporosis within 48 days to a serum vitamin D level of 50 nmol/L. PMID- 27189288 TI - Helmet CPAP versus Oxygen Therapy in Hypoxemic Acute Respiratory Failure: A Meta Analysis of Randomized Controlled Trials. AB - PURPOSE: The efficacy of helmet continuous positive airway pressure (CPAP) in hypoxemic acute respiratory failure (hARF) remains unclear. The aim of this meta analysis was to critically review studies that investigated the effect of helmet CPAP on gas exchange, mortality, and intubation rate in comparison with standard oxygen therapy. MATERIALS AND METHODS: We performed a meta-analysis of randomized controlled trials (RCTs) by searching the PubMed, Embase, Cochrane library, OVID, and CBM databases, and the bibliographies of the retrieved articles. Studies that enrolled adults with hARF who were treated with helmet CPAP and measured at least one of the following parameters were included: gas exchange, intubation rate, in hospital mortality rate. RESULTS: Four studies with 377 subjects met the inclusion criteria and were analyzed. Compared to the standard oxygen therapy, helmet CPAP significantly increased the PaO2/FiO2 [weighted mean difference (WMD)=73.40, 95% confidence interval (95% CI): 43.92 to 102.87, p<0.00001], and decreased the arterial carbon dioxide levels (WMD=-1.92, 95% CI: -3.21 to -0.63, p=0.003), intubation rate [relative risk (RR)=0.21, 95% CI: 0.11 to 0.40, p<0.00001], and in-hospital mortality rate (RR=0.22, 95% CI: 0.09 to 0.50, p=0.0004). CONCLUSION: The results of this meta-analysis suggest that helmet CPAP improves oxygenation and reduces mortality and intubation rates in hARF. However, the significant clinical and statistical heterogeneity of the literature implies that large RCTs are needed to determine the role of helmet CPAP in different hypoxemic ARF populations. PMID- 27189289 TI - AST-120 Improves Microvascular Endothelial Dysfunction in End-Stage Renal Disease Patients Receiving Hemodialysis. AB - PURPOSE: Endothelial dysfunction (ED) is a pivotal phenomenon in the development of cardiovascular disease (CVD) in patients receiving hemodialysis (HD). Indoxyl sulfate (IS) is a known uremic toxin that induces ED in patients with chronic kidney disease. The aim of this study was to investigate whether AST-120, an absorbent of IS, improves microvascular or macrovascular ED in HD patients. MATERIALS AND METHODS: We conducted a prospective, case-controlled trial. Fourteen patients each were enrolled in respective AST-120 and control groups. The subjects in the AST-120 group were treated with AST-120 (6 g/day) for 6 months. Microvascular function was assessed by laser Doppler flowmetry using iontophoresis of acetylcholine (Ach) and sodium nitroprusside (SNP) at baseline and again at 3 and 6 months. Carotid arterial intima-media thickness (cIMT) and flow-mediated vasodilation were measured at baseline and 6 months. The Wilcoxon rank test was used to compare values before and after AST-120 treatment. RESULTS: Ach-induced iontophoresis (endothelium-dependent response) was dramatically ameliorated at 3 months and 6 months in the AST-120 group. SNP-induced response showed delayed improvement only at 6 months in the AST-120 group. The IS level was decreased at 3 months in the AST-120 group, but remained stable thereafter. cIMT was significantly reduced after AST-120 treatment. No significant complications in patients taking AST-120 were reported. CONCLUSION: AST-120 ameliorated microvascular ED and cIMT in HD patients. A randomized study including a larger population will be required to establish a definitive role of AST-120 as a preventive medication for CVD in HD patients. PMID- 27189290 TI - The Effect of Pulsatility Index on Infarct Volume in Acute Lacunar Stroke. AB - PURPOSE: Lacunar stroke, in the context of small vessel disease, is a type of cerebral infarction caused by occlusion of a penetrating artery. Pulsatility index (PI) is an easily measurable parameter in Transcranial Doppler ultrasound (TCD) study. PI reflects distal cerebral vascular resistance and has been interpreted as a surrogate marker of small vessel disease. We hypothesized that an increased PI, a marker of small vessel disease, might be associated with a larger infarct volume in acute lacunar stroke. MATERIALS AND METHODS: This study included 64 patients with acute lacunar stroke who underwent TCD and brain MRI. We evaluated the association between the mean PI value of bilateral middle cerebral arteries and infarct volume on diffusion-weighted MRI using univariate and multivariate linear regression. RESULTS: The mean infarct volume and PI were 482.18+/-406.40 mm3 and 0.86+/-0.18, respectively. On univariate linear regression, there was a significant positive association between PI and infarct volume (p=0.001). In the multivariate model, a single standard deviation increase of PI (per 0.18) was associated with an increase of 139.05 mm3 in infarct volume (95% confidence interval, 21.25 to 256.85; p=0.022). CONCLUSION: We demonstrated that PI was an independent determinant of infarct volume in acute lacunar stroke. The PI value measured in acute stroke may be a surrogate marker of the extent of ischemic injury. PMID- 27189291 TI - Roux-en-Y Gastric Bypass vs. Sleeve Gastrectomy vs. Gastric Banding: The First Multicenter Retrospective Comparative Cohort Study in Obese Korean Patients. AB - PURPOSE: Bariatric surgery is relatively new in Korea, and studies comparing different bariatric procedures in Koreans are lacking. This study aimed to compare the clinical outcomes of laparoscopic adjustable gastric banding (LAGB), Roux-en-Y gastric bypass (RYGB), and sleeve gastrectomy (SG) for treating morbidly obese Korean adults. MATERIALS AND METHODS: In this multicenter retrospective cohort study, we reviewed the medical records of 261 obese patients who underwent different bariatric procedures. Clinical outcomes were measured in terms of weight loss and resolution of comorbidities, such as diabetes, hypertension, and dyslipidemia. Safety profiles for the procedures were also evaluated. RESULTS: In terms of weight loss, the three procedures showed similar results at 18 months (weight loss in 52.1% for SG, 61.0% for LAGB, and 69.2% for RYGB). Remission of diabetes, hypertension, and dyslipidemia was more frequent in patients who underwent RYGB (65.9%, 63.6%, and 100% of patients, respectively). Safety profiles were similar among groups. Early complications occurred in 26 patients (9.9%) and late complications in 32 (12.3%). In the LAGB group, five bands (6.9%) were removed. Among all patients, one death (1/261=0.38%) occurred in the RYGB group due to aspiration pneumonia. CONCLUSION: The three bariatric procedures were comparable in regards to weight-loss outcomes; nevertheless, RYGB showed a higher rate of comorbidity resolution. Bariatric surgery is effective and relatively safe; however, due to complications, some bands had to be removed in the LAGB group and a relatively high rate of reoperations was observed in the RYGB group. PMID- 27189292 TI - Comparison of Predicted Total Lung Capacity and Total Lung Capacity by Computed Tomography in Lung Transplantation Candidates. AB - PURPOSE: Lung size mismatch is a major cause of poor lung function and worse survival after lung transplantation (LTx). We compared predicted total lung capacity (pTLC) and TLC measured by chest computed tomography (TLC(CT)) in LTx candidates. MATERIALS AND METHODS: We reviewed the medical records of patients on waiting lists for LTx. According to the results of pulmonary function tests, patients were divided into an obstructive disease group and restrictive disease group. The differences between pTLC calculated using the equation of the European Respiratory Society and TLC(CT) were analyzed in each group. RESULTS: Ninety two patients met the criteria. Thirty five patients were included in the obstructive disease group, and 57 patients were included in the restrictive disease group. pTLC in the obstructive disease group (5.50+/-1.07 L) and restrictive disease group (5.57+/-1.03 L) had no statistical significance (p=0.747), while TLC(CT) in the restrictive disease group (3.17+/-1.15 L) was smaller than that I the obstructive disease group (4.21+/-1.38 L) (p<0.0001). TLC(CT)/pTLC was 0.770 in the obstructive disease group and 0.571 in the restrictive disease group. CONCLUSION: Regardless of pulmonary disease pattern, TLC(CT) was smaller than pTLC, and it was more apparent in restrictive lung disease. Therefore, we should consider the difference between TLC(CT) and pTLC, as well as lung disease patterns of candidates, in lung size matching for LTx. PMID- 27189293 TI - Surgical Anatomy of the Longus Colli Muscle and Uncinate Process in the Cervical Spine. AB - PURPOSE: There have been a few previous reports regarding the distances between the medial borders of the longus colli to expose the disc space. However, to our knowledge, there are no reports concerning longus colli dissection to expose the uncinate processes. This study was undertaken to assess the surgical relationship between the longus colli muscle and the uncinate process in the cervical spine. MATERIALS AND METHODS: This study included 120 Korean patients randomly selected from 333 who had cervical spine MRIs and CTs from January 2003 to October 2013. They consisted of 60 males and 60 females. Each group was subdivided into six groups by age from 20 to 70 years or more. We measured three parameters on MRIs from C3 to T1: left and right longus colli distance and inter-longus colli distance. We also measured three parameters on CT: left and right uncinate distance and inter-uncinate distance. RESULTS: The longus colli distances, uncinate distances, and inter-uncinate distances increased from C3 to T1. The inter-longus colli distances increased from C3 to C7. There was no difference in longus colli distances and uncinate distances between males and females. There was no difference in the six parameters for the different age groups. CONCLUSION: Although approximate guidelines, we recommend the longus colli be dissected approximately 5 mm at C3-5, 6 mm at C5-6, 7 mm at C6-7, and 8 mm at C7-T1 to expose the uncinate process to its lateral edge. PMID- 27189294 TI - Vascular Plug Assisted Retrograde Transvenous Obliteration (PARTO) for Gastric Varix Bleeding Patients in the Emergent Clinical Setting. AB - PURPOSE: To evaluate the technical feasibility and safety of vascular plug assisted retrograde transvenous obliteration (PARTO) for bleeding gastric varix performed in the emergent clinical setting and describe the mid-term clinical results. MATERIALS AND METHODS: From April 2012 to January 2015, emergent PARTO was tried in total 9 patients presented with active gastric varix bleeding. After initial insufficient or failure of endoscopic approach, they underwent PARTO in the emergent clinical setting. Gelatin sponge embolization of both gastrorenal (GR) shunt and gastric varix was performed after retrograde transvenous placement of a vascular plug in GR shunt. Coil assisted RTO (CARTO) was performed in one patient who had challenging GR shunt anatomy for vascular plug placement. Additional embolic materials, such as microcoils and NBCA glue-lipiodol mixture, were required in three patients to enhance complete occlusion of GR shunt or obliteration of competitive collateral vessels. Clinical success was defined as no variceal rebleeding and disappearance of gastric varix. RESULTS: All technical and clinical success-i.e., complete GR shunt occlusion and offending gastric varix embolization with immediate bleeding control-was achieved in all 9 patients. There was no procedure-related complication. All cases showed successful clinical outcome during mean follow up of 17 months (12-32 months), evidenced by imaging studies, endoscopy and clinical data. In 4 patients, mild worsening of esophageal varices or transient ascites was noted as portal hypertensive related change. CONCLUSION: Emergent PARTO is technically feasible and safe, with acceptable mid-term clinical results, in treating active gastric varix bleeding. PMID- 27189295 TI - Comparison of Dexmedetomidine and Remifentanil on Airway Reflex and Hemodynamic Changes during Recovery after Craniotomy. AB - PURPOSE: During emergence from anesthesia for a craniotomy, maintenance of hemodynamic stability and prompt evaluation of neurological status is mandatory. The aim of this prospective, randomized, double-blind study was to compare the effects of dexmedetomidine and remifentanil on airway reflex and hemodynamic change in patients undergoing craniotomy. MATERIALS AND METHODS: Seventy-four patients undergoing clipping of unruptured cerebral aneurysm were recruited. In the dexmedetomidine group, patients were administered dexmedetomidine (0.5 MUg/kg) for 5 minutes, while the patients of the remifentanil group were administered remifentanil with an effect site concentration of 1.5 ng/mL until endotracheal extubation. The incidence and severity of cough and hemodynamic variables were measured during the recovery period. Hemodynamic variables, respiration rate, and sedation scale were measured after extubation and in the post-anesthetic care unit (PACU). RESULTS: The incidence of grade 2 and 3 cough at the point of extubation was 62.5% in the dexmedetomidine group and 53.1% in the remifentanil group (p=0.39). Mean arterial pressure (p=0.01) at admission to the PACU and heart rate (p=0.04 and 0.01, respectively) at admission and at 10 minutes in the PACU were significantly lower in the dexmedetomidine group. Respiration rate was significantly lower in the remifentanil group at 2 minutes (p<0.01) and 5 minutes (p<0.01) after extubation. CONCLUSION: We concluded that a single bolus of dexmedetomidine (0.5 MUg/kg) and remifentanil infusion have equal effectiveness in attenuating coughing and hemodynamic changes in patients undergoing cerebral aneurysm clipping; however, dexmedetomidine leads to better preservation of respiration. PMID- 27189296 TI - Standard versus Rotation Technique for Insertion of Supraglottic Airway Devices: Systematic Review and Meta-Analysis. AB - PURPOSE: Supraglottic airway devices have been widely utilized as an alternative to tracheal intubation in various clinical situations. The rotation technique has been proposed to improve the insertion success rate of supraglottic airways. However, the clinical efficacy of this technique remains uncertain as previous results have been inconsistent, depending on the variable evaluated. MATERIALS AND METHODS: We systematically searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials in April 2015 for randomized controlled trials that compared the rotation and standard techniques for inserting supraglottic airways. RESULTS: Thirteen randomized controlled trials (1505 patients, 753 with the rotation technique) were included. The success rate at the first attempt was significantly higher with the rotation technique than with the standard technique [relative risk (RR): 1.13; 95% confidence interval (CI): 1.05 to 1.23; p=0.002]. The rotation technique provided significantly higher overall success rates (RR: 1.06; 95% CI: 1.04 to 1.09; p<0.001). Device insertion was completed faster with the rotation technique (mean difference: -4.6 seconds; 95% CI: -7.37 to -1.74; p=0.002). The incidence of blood staining on the removed device (RR: 0.36; 95% CI: 0.27 to 0.47; p<0.001) was significantly lower with the rotation technique. CONCLUSION: The rotation technique provided higher first-attempt and overall success rates, faster insertion, and a lower incidence of blood on the removed device, reflecting less mucosal trauma. Thus, it may be considered as an alternative to the standard technique when predicting or encountering difficulty in inserting supraglottic airways. PMID- 27189297 TI - Intranasally Administered Adjunctive Dexmedetomidine Reduces Perioperative Anesthetic Requirements in General Anesthesia. AB - PURPOSE: Intranasal dexmedetomidine is an effective sedative for premedication and is regularly used to reduce preoperative tension and anxiety in children. This study aimed to assess the effect of intranasally adjunctive dexmedetomidine on perioperative sedative and analgesic requirements in adults. MATERIALS AND METHODS: Patients were randomly divided into four groups to receive preoperative administration of saline, intranasal dexmedetomidine 1 MUg/kg and 2 MUg/kg, and intravenous dexmedetomidine 1 MUg/kg, respectively. Propofol and remifentanil were target-controlled infused to maintain intraoperative bispectral index at 45 55 and blood pressure at baseline value+/-20%. Sufentanil was administered to maintain postoperative visual analogue scale <=3. Perioperative anesthetics requirements were compared using nonparametric tests. RESULTS: Intranasal dexmedetomidine significantly attenuated propofol requirements for anesthesia induction and maintenance in a dose-dependent manner. Patients given intranasal dexmedetomidine 2 MUg/kg required less remifentanil for anesthesia maintenance. The first postoperative request for sufentanil analgesia was delayed in patients given intranasal dexmedetomidine 2 MUg/kg. The anesthetics-sparing effect of intranasal dexmedetomidine was significantly weaker than intravenous dexmedetomidine at the same dose of 1 MUg/kg. The incidences of adverse events, including hemodynamic instability and delayed recovery, were comparable with and without intranasal dexmedetomidine. CONCLUSION: Intranasal administration of dexmedetomidine can reduce perioperative anesthetic requirements, and a dose of dexmedetomidine 2 MUg/kg produces a better effect in adults. The anesthetics sparing effect of intranasal dexmedetomidine 1 MUg/kg is less than that with the same intravenous dose of dexmedetomidine. PMID- 27189299 TI - Factors Contributing to Increases in Prescription Drug Expenditures Borne by National Health Insurance in South Korea. AB - PURPOSE: Rapid growth of prescription drug expenditures is a problem in South Korea. The objective of this study was to assess the contributions of four variables (therapeutic choice, drug-mix, original use, and price changes) to increases in drug expenditures paid by the National Health Insurance (NHI) in Korea. MATERIALS AND METHODS: A retrospective cohort study was conducted between January 1, 2008 and June 30, 2012 utilizing data from the NHI Claims Database of the Health Insurance Review and Assessment Service. The number of target drug types for final analysis was 13959. To analyze the growth rates of drug expenditures, this study used Fisher ideal index and the Laspeyres and Paasche indexes. RESULTS: With the exception of 2012, therapeutic choice contributed to about 40-60% of the increase in drug expenditures every year, while drug-mix contributed to another 30-40%. CONCLUSION: The rapid growth in prescription drug expenditure was found to be largely due to drug-mix and therapeutic choice over time. Original use had little impact on drug spending. PMID- 27189298 TI - Preclinical Study of Cell Therapy for Osteonecrosis of the Femoral Head with Allogenic Peripheral Blood-Derived Mesenchymal Stem Cells. AB - PURPOSE: To explore the value of transplanting peripheral blood-derived mesenchymal stem cells from allogenic rabbits (rPBMSCs) to treat osteonecrosis of the femoral head (ONFH). MATERIALS AND METHODS: rPBMSCs were separated/cultured from peripheral blood after granulocyte colony-stimulating factor mobilization. Afterwards, mobilized rPBMSCs from a second passage labeled with PKH26 were transplanted into rabbit ONFH models, which were established by liquid nitrogen freezing, to observe the effect of rPBMSCs on ONFH repair. Then, the mRNA expressions of BMP-2 and PPAR-gamma in the femoral head were assessed by RT-PCR. RESULTS: After mobilization, the cultured rPBMSCs expressed mesenchymal markers of CD90, CD44, CD29, and CD105, but failed to express CD45, CD14, and CD34. The colony forming efficiency of mobilized rPBMSCs ranged from 2.8 to 10.8 per million peripheral mononuclear cells. After local transplantation, survival of the engrafted cells reached at least 8 weeks. Therein, BMP-2 was up-regulated, while PPAR-gamma mRNA was down-regulated. Additionally, bone density and bone trabeculae tended to increase gradually. CONCLUSION: We confirmed that local transplantation of rPBMSCs benefits ONFH treatment and that the beneficial effects are related to the up-regulation of BMP-2 expression and the down regulation of PPAR-gamma expression. PMID- 27189301 TI - Robotic Single-Site(r) Sacrocolpopexy: First Report and Technique Using the Single-Site(r) Wristed Needle Driver. AB - The recently introduced da Vinci Single-Site(r) platform offers cosmetic benefits when compared with standard Multi-Site(r) robotic surgery. The innovative endowristed technology has increased the use of the da Vinci Single-Site(r) platform. The newly introduced Single-Site(r) Wristed Needle Driver has made it feasible to perform various surgeries that require multiple laparoscopic sutures and knot tying. Laparoscopic sacrocolpopexy is also a type of technically difficult surgery requiring multiple sutures, and there have been no reports of it being performed using the da Vinci Single-Site(r) platform. Thus, to the best of our knowledge, this is the first report of robotic single-site (RSS) sacrocolpopexy, and I found this procedure to be feasible and safe. All RSS procedures were completed successfully. The mean operative time was 122.17+/ 22.54 minutes, and the mean blood loss was 66.67+/-45.02 mL. No operative or major postoperative complications occurred. Additional studies should be performed to assess the benefits of RSS sacrocolpopexy. I present the first six cases of da Vinci Single-Site(r) surgery in urogynecology and provide a detailed description of the technique. PMID- 27189300 TI - Surgical Treatment for Falcotentorial Meningiomas. AB - Among intracranial meningiomas, falcotentorial meningiomas, occurring at the junction of the falx cerebri and tentorial dural folds, are extremely rare. Because of their deep location, they are surrounded by critical structures, and have been regarded as one of the most challenging lesions for surgical treatment. In this study, we describe our surgical strategy for falcotentorial meningiomas and provide a review of our experience. PMID- 27189302 TI - In Vitro Activity of Tigecycline Against Orientia tsutsugamushi. AB - Scrub typhus is a zoonosis caused by Orientia tsutsugamushi (O. tsutsugamushi) occurring mainly in autumn in Korea. The need of new antibiotics has arisen with a report on strains resistant to antibiotics and chronic infection. This study aims to identify susceptibility of tigecycline in-vitro as a new therapeutic option for O. tsutsugamushi. Antibacterial activity of tigecycline against the O. tsutsugamushi was compared with doxycycline using flow cytometry assay. The inhibitory concentration 50 (IC50) was 3.59*10-3 MUg/mL in doxycycline-treated group. Whereas in 0.71*10-3 MUg/mL tigecycline-treated group. These findings indicate that tigecycline may be a therapeutic option for the treatment of scrub typhus. PMID- 27189303 TI - The Effect of Xanthigen on the Expression of Brown Adipose Tissue Assessed by 18F FDG PET. AB - Brown adipose tissue (BAT) is related with energy expenditure, in contrary to fat storing white adipose tissue. Recent studies have shown that cold exposure could be related with the expression of BAT in adult subjects assessed by 18F fluorodeoxyglucose (FDG) positron emission tomography (PET). In addition, the application in previous clinical trials showed positive effect of xanthigen containing fucoxanthin and punicic acid on body weight and liver fat content. In this short-term intervention study, we evaluated the effect of xanthigen on the expression of BAT by 18F-FDG PET. Two healthy obese premenopausal women were enrolled and xanthigen 600 mg (2 capsules including fucoxanthin 3 mg, punicic acid 174 mg) was given for 3 months without dietary and exercise intervention. Body composition and dietary intake were assessed monthly. Laboratory test and 18F-FDG PET were performed before and after intervention. After intervention, there was neither weight reduction nor remarkable laboratory change. However, BAT, assessed by 18F-FDG PET, was detected in both cervical, supraclavicular and paravertebral space in one subject, even though her body weight showed mild increase. This result suggested that xanthigen can induce BAT in a healthy adult. However, a further large well-controlled study is needed. PMID- 27189304 TI - Unmasking Granulomatous Pneumocystis jirovecii Pneumonia with Nodular Opacity in an HIV-Infected Patient after Initiation of Antiretroviral Therapy. AB - Pneumocystis jirovecii pneumonia (PJP) in patients with HIV infection can, in rare cases, present with pulmonary nodules that histologically involve granulomatous inflammation. This report describes an intriguing case of granulomatous PJP with pulmonary nodules after commencing antiretroviral therapy (ART) in an HIV-infected patient without respiratory signs or symptoms. Diagnosis of granulomatous PJP was only achieved through thoracoscopic lung biopsy. This case suggests that granulomatous PJP should be considered in the differential diagnosis of pulmonary nodules in HIV-infected patients for unmasking immune reconstitution inflammatory syndrome manifestation after initiation of ART. PMID- 27189305 TI - Arbekacin as an Alternative Drug to Teicoplanin for the Treatment of MRSA Infection. PMID- 27189306 TI - Erratum to "A Great Teacher of Neurosurgery in Korea: Hun Jae Lee (1921-1983)" by Shin DA, et al. (Yonsei Med J 2016;57:539-41.). AB - This corrects the article on p. 539 in vol. 57, PMID: 26996549. PMID- 27189307 TI - Erratum to "Snakebite in Korea: A Guideline to Primary Surgical Management" by Rha JH, et al. (Yonsei Med J 2015;56:1443-8.). AB - This corrects the article on p. 1443 in vol. 56, PMID: 26256993. PMID- 27189308 TI - Erratum to "Finite Element Analysis for Comparison of Spinous Process Osteotomies Technique with Conventional Laminectomy as Lumbar Decompression Procedure" by Kim HJ, et al. (Yonsei Med J 2015;56:146-53.). AB - This corrects the article on p. 146 in vol. 56, PMID: 25510758. PMID- 27189309 TI - The Pulmonary Hypertension Consult: Clinical and Coding Considerations. AB - Pulmonary hypertension (PH) is an increasingly recognized cause of morbidity and mortality, and in the past 20 years, there has been a rapid expansion in research and available therapies. Although it is defined quite simply as a mean pulmonary arterial pressure of >= 25 mm Hg, PH encompasses a heterogeneous group of disease processes. In the past, PH was classified as primary or secondary, but as understanding of the various contributing diseases has increased, classification systems have attempted to group these diseases by clinical features and disease mechanism. The evaluation of patients with suspected PH can be cumbersome, and a careful and methodical approach is needed to ensure timely and accurate diagnosis, correct physiological classification, and appropriate treatment. In this review, we discuss the classification and diagnostic evaluation of PH in adults as well as some of the billing and coding considerations involved in this evaluation. PMID- 27189310 TI - Endobronchial Ultrasound: Clinical Uses and Professional Reimbursements. AB - Endobronchial ultrasonography (EBUS) has become an invaluable tool in the diagnosis of patients with a variety of thoracic abnormalities. The majority of EBUS procedures are used to diagnose and stage mediastinal and hilar abnormalities, as well as peripheral pulmonary targets, with a probe-based technology. Nearly 1,000 articles have been written about its use and utility. New Current Procedural Terminology (CPT) codes have been introduced in 2016 to better capture the work and clinical use associated with the various types of EBUS procedures. The existing 31620 code has been deleted and replaced by three new codes: 31652, 31653, and 31654. These new codes have been through the valuation process, and the new rule for reimbursement has been active since January 1, 2016 with National Correct Coding Initiative correction as of April 1, 2016. The impact of these new codes will result in a net reduction in professional and technical reimbursement. This article describes the current use of EBUS and explains the current codes and professional reimbursement. PMID- 27189311 TI - Full Monte Carlo and measurement-based overall performance assessment of improved clinical implementation of eMC algorithm with emphasis on lower energy range. AB - New version 13.6.23 of the electron Monte Carlo (eMC) algorithm in Varian EclipseTM treatment planning system has a model for 4MeV electron beam and some general improvements for dose calculation. This study provides the first overall accuracy assessment of this algorithm against full Monte Carlo (MC) simulations for electron beams from 4MeV to 16MeV with most emphasis on the lower energy range. Beams in a homogeneous water phantom and clinical treatment plans were investigated including measurements in the water phantom. Two different material sets were used with full MC: (1) the one applied in the eMC algorithm and (2) the one included in the EclipseTM for other algorithms. The results of clinical treatment plans were also compared to those of the older eMC version 11.0.31. In the water phantom the dose differences against the full MC were mostly less than 3% with distance-to-agreement (DTA) values within 2mm. Larger discrepancies were obtained in build-up regions, at depths near the maximum electron ranges and with small apertures. For the clinical treatment plans the overall dose differences were mostly within 3% or 2mm with the first material set. Larger differences were observed for a large 4MeV beam entering curved patient surface with extended SSD and also in regions of large dose gradients. Still the DTA values were within 3mm. The discrepancies between the eMC and the full MC were generally larger for the second material set. The version 11.0.31 performed always inferiorly, when compared to the 13.6.23. PMID- 27189312 TI - Mobile Health Insurance System and Associated Costs: A Cross-Sectional Survey of Primary Health Centers in Abuja, Nigeria. AB - BACKGROUND: Nigeria contributes only 2% to the world's population, accounts for 10% of the global maternal death burden. Health care at primary health centers, the lowest level of public health care, is far below optimal in quality and grossly inadequate in coverage. Private primary health facilities attempt to fill this gap but at additional costs to the client. More than 65% Nigerians still pay out of pocket for health services. Meanwhile, the use of mobile phones and related services has risen geometrically in recent years in Nigeria, and their adoption into health care is an enterprise worth exploring. OBJECTIVE: The purpose of this study was to document costs associated with a mobile technology supported, community-based health insurance scheme. METHODS: This analytic cross sectional survey used a hybrid of mixed methods stakeholder interviews coupled with prototype throw-away software development to gather data from 50 public primary health facilities and 50 private primary care centers in Abuja, Nigeria. Data gathered documents costs relevant for a reliable and sustainable mobile supported health insurance system. Clients and health workers were interviewed using structured questionnaires on services provided and cost of those services. Trained interviewers conducted the structured interviews, and 1 client and 1 health worker were interviewed per health facility. Clinic expenditure was analyzed to include personnel, fixed equipment, medical consumables, and operation costs. Key informant interviews included a midmanagement staff of a health-management organization, an officer-level staff member of a mobile network operator, and a mobile money agent. RESULTS: All the 200 respondents indicated willingness to use the proposed system. Differences in the cost of services between public and private facilities were analyzed at 95% confidence level (P<.001). This indicates that average out-of-pocket cost of services at private health care facilities is significantly higher than at public primary health care facilities. Key informant interviews with a health management organizations and a telecom operator revealed high investment interests. Cost documentation analysis of income versus expenditure for the major maternal and child health service areas-antenatal care, routine immunization, and birth attendance for 1 year showed that primary health facilities would still profit if technology-supported, health insurance schemes were adopted. CONCLUSIONS: This study demonstrates a case for the implementation of enrolment, encounter management, treatment verification, claims management and reimbursement using mobile technology for health insurance in Abuja, Nigeria. Available data show that the introduction of an electronic job aid improved efficiency. Although it is difficult to make a concrete statement on profitability of this venture but the interest of the health maintenance organizations and telecom experts in this endeavor provides a positive lead. PMID- 27189313 TI - Ketoconazole-induced estrogen deficiency causes transient decrease in placental blood flow associated with hypoxia and later placental weight gain in rats. AB - This study investigated the relationship among estrogen, placental blood flow and placental weight gain in rats treated with ketoconazole. Oral administration of ketoconazole (25mg/kg/day) on Days 12-14 of pregnancy induced reduction of plasma estradiol-17beta (E2) concentration, transient decrease in placental blood flow and increased intensity of a hypoxia-related marker in the placenta on Day 14 of pregnancy. On Day 20 of pregnancy, placental weights of ketoconazole-treated rats increased when compared to controls. Histologically, maternal sinusoidal area of the placenta decreased on Day 14 of pregnancy and the total area of maternal and fetal sinusoids increased on Day 20. All the changes disappeared by concomitant subcutaneous infusion of E2. These results indicate that ketoconazole-induced E2 deficiency causes transient decrease in placental blood flow associated with hypoxia and later placental weight gain in rats. PMID- 27189314 TI - Association between paraben exposure and menstrual cycle in female university students in Japan. AB - Parabens have been known to have estrogenic activity in many in vivo and in vitro studies and biomonitoring data indicated ubiquitous exposure in general populations. However, there are few human studies on reproductive effects of parabens. In this study, menstrual cycle length and its intra-individual variation were investigated by bleeding record over the period of 5 months and urinary concentrations of parabens were measured for 128 female Japanese university students. We found significantly negative relationships between menstrual cycle length and urinary estrogen-equivalent total paraben (odds=0.73, 95% CI 0.56-0.96) and butyl paraben concentrations (odds=0.83, 0.70-0.99), which indicated shortened cycle length in women with high urinary paraben concentrations. This study indicated that paraben exposure at not excessive levels is associated with menstrual cycle length or its variability among general female subjects. These results suggest a possibility that parabens exposure is one of the environmental causes of human reproductive problem. PMID- 27189315 TI - The human placental proteome is affected by maternal smoking. AB - Detrimental effects of maternal smoking on the term placental proteome and steroid-metabolizing activities, and maternal hormone levels, were studied by using seven non-smoker and seven smoker placentae. Smoking significantly affected 18% of protein spots. The functional networks affected were i) cell morphology, cellular assembly and organization, cellular compromise (15 hits) and ii) DNA replication, recombination, and repair, energy production, nucleic acid metabolism (6 hits). Smoking significantly up-regulated such proteins as, SERPINA1, EFHD1 and KRT8; and down-regulated SERPINB2, FGA and HBB. Although maternal plasma steroids were not significantly altered, the catalytic activity of CYP1A1 was increased whereas CYP19A1 activity was reduced by smoking. Furthermore, transcript expression of CYP1A1 and CYP4B1 were induced while HSD17B2, NFKB and TGFB1 were repressed by smoking. The observed smoking induced wide-spread changes on placental proteome and transcript levels may contribute to the lowered birth weights of the new-born child and placenta. PMID- 27189316 TI - Multisensory signalling enhances pupil dilation. AB - Detecting and integrating information across the senses is an advantageous mechanism to efficiently respond to the environment. In this study, a simple auditory-visual detection task was employed to test whether pupil dilation, generally associated with successful target detection, could be used as a reliable measure for studying multisensory integration processing in humans. We recorded reaction times and pupil dilation in response to a series of visual and auditory stimuli, which were presented either alone or in combination. The results indicated faster reaction times and larger pupil diameter to the presentation of combined auditory and visual stimuli than the same stimuli when presented in isolation. Moreover, the responses to the multisensory condition exceeded the linear summation of the responses obtained in each unimodal condition. Importantly, faster reaction times corresponded to larger pupil dilation, suggesting that also the latter can be a reliable measure of multisensory processes. This study will serve as a foundation for the investigation of auditory-visual integration in populations where simple reaction times cannot be collected, such as developmental and clinical populations. PMID- 27189317 TI - Association of mGFR of the Remaining Kidney Divided by Its Volume before Donation with Functional Gain in mGFR among Living Kidney Donors. AB - BACKGROUND AND OBJECTIVES: The predictors of long-term renal function in living kidney donors are currently discussed. Our objectives were to describe the predictors of functional gain of the remaining kidney after kidney donation. We hypothesized that GFR of the remaining kidney divided by volume of this kidney (rk-GFR/vol) would reflect the density of functional nephrons and be inversely associated with functional gain of the remaining kidney. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a prospective monocentric study including 63 living donors (26 men; 50.3+/-11.8 years old) who had been evaluated for (51)Cr-EDTA and measured GFR, split renal function by scintigraphy before donation (between 2004 and 2009), and measured GFR at 5.7+/-0.5 years after donation. For 52 donors, volume of the remaining kidney (measured and estimated with the ellipsoid formula using renal computed tomography scannography) was determined before donation. We tested our hypothesis in an external validation cohort of 39 living donors (13 men; 51.0+/-9.4 years old) from another single center during the same time period. RESULTS: For the main cohort, the mean measured GFR was 97.6+/-13.0 ml/min per 1.73 m(2) before donation and 63.8+/-9.4 ml/min per 1.73 m(2) at 5 years. Functional gain averaged 16.2+/-7.2 ml/min per 1.73 m(2) (+35.3%+/-16.7%). Multivariate analysis showed that age, body mass index, and rk-GFR/vol at donation were negatively correlated with functional gain and had strong predictive power of the 5-year functional gain (adjusted 5-year functional gain for age: -0.4 [95% confidence interval (95% CI), -0.5 to -0.1]; body mass index: -0.3 [95% CI, -0.6 to -0.1]; rk-GFR/vol: -55.1 [95% CI, -92.3 to -17.9]). We tested this model in the external validation cohort (adjusted 5-year functional gain for age: -0.1 [95% CI, -0.5 to 0.3]; body mass index: -0.9 [95% CI, -1.8 to -0.1]; rk-GFR/vol: -97.6 [95% CI, -137.5 to -57.6]) and confirmed that rk-GFR/vol was inversely associated with 5-year functional gain. CONCLUSIONS: For given age and body mass index, the long-term functional gain of the remaining kidney is inversely associated with the new variable rk-GFR/vol at donation. PMID- 27189319 TI - Birth outcomes after exposure to mebendazole and pyrvinium during pregnancy - A Danish nationwide cohort study. AB - Mebendazole and pyrvinium are anthelmintics used to treat infections with pinworms, a common infection in children. Other indications for treatment with mebendazole are infections with soil-transmitted helminths. These infections are rare in Denmark, but affect more than 1.5 billion people worldwide. Limited safety data of anthelmintics during pregnancy exists and the purpose of this study was to investigate the association between exposure to mebendazole or pyrvinium during pregnancy and the adverse pregnancy outcomes: congenital malformations, stillbirths, neonatal mortality and small for gestational age. The Danish Fertility Database was used to identify all births in Denmark from 1997 to 2007. Maternal exposure to anthelmintics was identified through The Danish Prescription Registry. Of 713667 births, 2567 mothers redeemed a prescription for mebendazole; 1588 for pyrvinium. Logistic regression analysis adjusted for potential confounders. We found no association between exposure to mebendazole and major congenital malformations (OR = 0.7 (CI 95% 0.5-1.1)) or other negative birth outcomes and we found no association between exposure to pyrvinium and major congenital malformations (OR = 0.8 (CI 95% 0.4-1.5)) or other negative birth outcomes. No increased risk was found of having negative birth outcomes after exposure at any trimester during pregnancy. PMID- 27189318 TI - Association of Urinary Biomarkers of Inflammation, Injury, and Fibrosis with Renal Function Decline: The ACCORD Trial. AB - BACKGROUND AND OBJECTIVES: Current measures for predicting renal functional decline in patients with type 2 diabetes with preserved renal function are unsatisfactory, and multiple markers assessing various biologic axes may improve prediction. We examined the association of four biomarker-to-creatinine ratio levels (monocyte chemotactic protein-1, IL-18, kidney injury molecule-1, and YKL 40) with renal outcome. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used a nested case-control design in the Action to Control Cardiovascular Disease Trial by matching 190 participants with >=40% sustained eGFR decline over the 5-year follow-up period to 190 participants with <=10% eGFR decline in a 1:1 fashion on key characteristics (age within 5 years, sex, race, baseline albumin-to creatinine ratio within 20 MUg/mg, and baseline eGFR within 10 ml/min per 1.73 m(2)), with <=10% decline. We used a Mesoscale Multiplex Platform and measured biomarkers in baseline and 24-month specimens, and we examined biomarker associations with outcome using conditional logistic regression. RESULTS: Baseline and 24-month levels of monocyte chemotactic protein-1-to-creatinine ratio levels were higher for cases versus controls. The highest quartile of baseline monocyte chemotactic protein-1-to-creatinine ratio had fivefold greater odds, and each log increment had 2.27-fold higher odds for outcome (odds ratio, 5.27; 95% confidence interval, 2.19 to 12.71 and odds ratio, 2.27; 95% confidence interval, 1.44 to 3.58, respectively). IL-18-to-creatinine ratio, kidney injury molecule-1-to-creatinine ratio, and YKL-40-to-creatinine ratio were not consistently associated with outcome. C statistic for traditional predictors of eGFR decline was 0.70, which improved significantly to 0.74 with monocyte chemotactic protein-1-to-creatinine ratio. CONCLUSIONS: Urinary monocyte chemotactic protein-1-to-creatinine ratio concentrations were strongly associated with sustained renal decline in patients with type 2 diabetes with preserved renal function. PMID- 27189320 TI - Specific enrichment of 2-arachidonoyl-lysophosphatidylcholine in carotid atheroma plaque from type 2 diabetic patients. AB - BACKGROUND AND AIMS: Diabetic patients are at high risk of stroke and coronary artery disease. Recent data suggest that arachidonic acid metabolism is altered in diabetic conditions and that these alterations contribute to accelerated atherosclerosis. Little is known about how these alterations affect the metabolism and the proportions of different lipid species within the atherosclerotic plaque. The aim of our study was to perform a targeted lipidomic analysis of human atherosclerotic lesions, with a specific focus on PUFA containing lipid species, to reveal differences in the fatty-acid composition of plaque in diabetic patients compared with non-diabetic controls. METHODS: Carotid atheroma plaque samples were obtained from 31 diabetic and 48 non-diabetic patients undergoing carotid endarterectomy. Targeted lipidomic analysis was then performed to determine the fatty acid composition of major glycerophospholipids and cholesteryl ester species by liquid chromatography-tandem mass spectrometry. RESULTS: Atheroma plaques from diabetic patients were significantly enriched with 2-arachidonoyl-lysophosphatidylcholine (2-AA-LPC) (2.3 +/- 0.8% Vs. 1.8 +/- 0.6% p = 0.0002). Multivariable logistic regression showed that an increased 2-AA-LPC level was independently associated with diabetes. Finally, a positive relationship was found between 2-AA-LPC and HbA1c levels. Interestingly, endothelial lipase and calcium independent PLA2 gamma which could account for the production of 2-AA-LPC were detected in carotid plaques by immunohistochemistry. CONCLUSIONS: 2-AA-LPC stands at the crossroads of major metabolic pathways that lead to the synthesis of bioactive molecules such as AA-derived eicosanoids, 2-AA lysophosphatidic acid and 2-AA-glycerol. 2-AA-LPC therefore appears to be a promising molecule to investigate in the context of diabetes. PMID- 27189322 TI - RECIST 1.1-Update and clarification: From the RECIST committee. AB - The Response Evaluation Criteria in Solid Tumours (RECIST) were developed and published in 2000, based on the original World Health Organisation guidelines first published in 1981. In 2009, revisions were made (RECIST 1.1) incorporating major changes, including a reduction in the number of lesions to be assessed, a new measurement method to classify lymph nodes as pathologic or normal, the clarification of the requirement to confirm a complete response or partial response and new methodologies for more appropriate measurement of disease progression. The purpose of this paper was to summarise the questions posed and the clarifications provided as an update to the 2009 publication. PMID- 27189321 TI - Mechanical slowing-down of cytoplasmic diffusion allows in vivo counting of proteins in individual cells. AB - Many key regulatory proteins in bacteria are present in too low numbers to be detected with conventional methods, which poses a particular challenge for single cell analyses because such proteins can contribute greatly to phenotypic heterogeneity. Here we develop a microfluidics-based platform that enables single molecule counting of low-abundance proteins by mechanically slowing-down their diffusion within the cytoplasm of live Escherichia coli (E. coli) cells. Our technique also allows for automated microscopy at high throughput with minimal perturbation to native physiology, as well as viable enrichment/retrieval. We illustrate the method by analysing the control of the master regulator of the E. coli stress response, RpoS, by its adapter protein, SprE (RssB). Quantification of SprE numbers shows that though SprE is necessary for RpoS degradation, it is expressed at levels as low as 3-4 molecules per average cell cycle, and fluctuations in SprE are approximately Poisson distributed during exponential phase with no sign of bursting. PMID- 27189324 TI - Skeletal effect of casein and whey protein intake during catch-up growth in young male Sprague-Dawley rats. AB - The aim of the present study was to determine whether the type of protein ingested influences the efficiency of catch-up (CU) growth and bone quality in fast-growing male rats. Young male Sprague-Dawley rats were either fed ad libitum (controls) or subjected to 36 d of 40 % food restriction followed by 24 or 40 d of re-feeding with either standard rat chow or iso-energetic, iso-protein diets containing milk proteins - casein or whey. In terms of body weight, CU growth was incomplete in all study groups. Despite their similar food consumption, casein-re fed rats had a significantly higher body weight and longer humerus than whey-re fed rats in the long term. The height of the epiphyseal growth plate (EGP) in both casein and whey groups was greater than that of rats re-fed normal chow. Microcomputed tomography yielded significant differences in bone microstructure between the casein and whey groups, with the casein-re-fed animals having greater cortical thickness in both the short and long term in addition to a higher trabecular bone fraction in the short term, although this difference disappeared in the long term. Mechanical testing confirmed the greater bone strength in rats re-fed casein. Bone quality during CU growth significantly depends on the type of protein ingested. The higher EGP in the casein- and whey-re-fed rats suggests a better growth potential with milk-based diets. These results suggest that whey may lead to slower bone growth with reduced weight gain and, as such, may serve to circumvent long-term complications of CU growth. PMID- 27189323 TI - A phase I study of S-1 in combination with nab-paclitaxel in patients with unresectable or recurrent gastric cancer. AB - BACKGROUND: In Japan, S-1, an oral fluoropyrimidine, plus cisplatin is a standard regimen for advanced gastric cancer, whereas nab-paclitaxel is a treatment option. We aimed to evaluate the tolerance, pharmacokinetics, safety, and clinical efficacy of S-1 combined with nab-paclitaxel in patients with advanced gastric cancer in a phase 1 study. METHODS: The primary objective was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of S-1 plus nab-paclitaxel. The study was designed in accordance with a standard 3 + 3 method. Patients received 3-week cycles of treatment. S-1 was administered orally at 80 mg/m2 twice daily for 14 days, and nab-paclitaxel was administered as an intravenous infusion at 180, 220, or 260 mg/m2 on day 1 or 8. RESULTS: Among the 16 patients enrolled, dose-limiting toxicity was observed in one patient at level 2a (S-1 80 mg/m2 twice daily plus nab-paclitaxel 220 mg/m2 on day 1). The MTD was not obtained, but the RD was established as level 3a (S-1 80 mg/m2 twice daily plus nab-paclitaxel 260 mg/m2 on day 1). The most common grade 3-4 toxicity was neutropenia (62.5 %). The overall response rate was 54.5 %. The pharmacokinetic profiles of coadministered S-1 and paclitaxel were comparable to those of nab paclitaxel or S-1 alone. CONCLUSIONS: Based on the present results, the RD was determined as level 3a (S-1 80 mg/m2 twice daily plus nab-paclitaxel 260 mg/m2 on day 1). This combination therapy was well tolerated and showed antitumor efficacy in patients with advanced gastric cancer. PMID- 27189326 TI - Cranial ultrasonography of the immature cerebellum: Role and limitations. AB - Cranial ultrasonography (CUS) is a reliable and non-invasive tool to detect frequently occurring brain abnormalities and to monitor brain development and maturation in high risk neonates. Standard CUS views are obtained through the anterior fontanel. However, evaluation of the posterior fossa is often suboptimal with this approach. Cerebellar injury occurs frequently in preterm infants and has important prognostic consequences. Early detection is therefore important. This review focuses on techniques that optimize the performance of CUS when studying the preterm cerebellum, including the use of the mastoid fontanel and the adaptation of focus points and scan frequencies. For illustration, CUS images of the normal posterior fossa anatomy as well as examples of abnormalities that may be encountered in preterm infants are included. We also discuss the limitations of CUS and the role of magnetic resonance imaging. PMID- 27189325 TI - Polar flagella rotation in Vibrio parahaemolyticus confers resistance to bacteriophage infection. AB - Bacteriophage has been recognized as a novel approach to treat bacterial infectious diseases. However, phage resistance may reduce the efficacy of phage therapy. Here, we described a mechanism of bacterial resistance to phage infections. In Gram-negative enteric pathogen Vibrio parahaemolyticus, we found that polar flagella can reduce the phage infectivity. Deletion of polar flagella, but not the lateral flagella, can dramatically promote the adsorption of phage to the bacteria and enhances the phage infectivity to V. parahaemolyticus, indicating that polar flagella play an inhibitory role in the phage infection. Notably, it is the rotation, not the physical presence, of polar flagella that inhibits the phage infection of V. parahaemolyticus. Strikingly, phage dramatically reduces the virulence of V. parahaemolyticus only when polar flagella were absent both in vitro and in vivo. These results indicated that polar flagella rotation is a previously unidentified mechanism that confers bacteriophage resistance. PMID- 27189327 TI - Primary Low Level of High-Density Lipoprotein Cholesterol and Risks of Coronary Heart Disease, Cardiovascular Disease, and Death: Results From the Multi-Ethnic Study of Atherosclerosis. AB - Prior studies observing associations between low levels of high-density lipoprotein (HDL) cholesterol and cardiovascular disease (CVD) have often been conducted among persons with metabolic or other lipid abnormalities. In this study, we investigated the association between primary low HDL cholesterol and coronary heart disease (CHD), CVD, and all-cause death after adjustment for confounders in the Multi-Ethnic Study of Atherosclerosis (MESA). Participants who were free of clinical CVD were recruited from 6 US research centers from 2000 to 2002 and followed for a median duration of 10.2 years. We defined "primary low HDL cholesterol" as HDL cholesterol level <40 mg/dL (men) or <50 mg/dL (women), triglyceride level <100 mg/dL, and low-density lipoprotein cholesterol level <100 mg/dL (n = 158). We defined an "optimal" lipid profile as HDL cholesterol >=40 mg/dL (men) or >=50 mg/dL (women) and triglycerides and low-density lipoprotein cholesterol <100 mg/dL (n = 780). For participants with primary low HDL cholesterol versus those with an optimal lipid profile, adjusted hazard ratios for total CHD, CVD, and death were 2.25 (95% confidence interval (CI): 1.20, 4.21; P = 0.011), 1.93 (95% CI: 1.11, 3.34; P = 0.020), and 1.11 (95% CI: 0.67, 1.84; P = 0.69), respectively. Participants with primary low HDL cholesterol had higher risks of CHD and CVD than participants with optimal lipid profiles but no difference in survival after a median 10.2 years of follow-up. PMID- 27189328 TI - Associations Between Vitamin D Level and Hospitalizations With and Without an Infection in a National Cohort of Medicare Beneficiaries. AB - Research has implicated low 25-hydroxyvitamin D (25(OH)D) level as a risk factor for infection; however, results have not been consistent. To further determine the nature of this relationship, we conducted a cohort study using Medicare beneficiaries participating in the 2001-2002 and 2003-2004 cycles of the National Health and Nutrition Examination Survey with data individually linked to hospital records from the Centers for Medicare and Medicaid Services. The primary exposure was a 25(OH)D level of <15 ng/mL versus >=15 ng/mL. The outcomes were a hospitalization with or without an infection within 1 year of participation in the National Health and Nutrition Examination Survey, as determined from the final hospital discharge codes (International Classification of Diseases, Ninth Revision, Clinical Modification). Of 1,713 individuals, 348 had a baseline serum 25(OH)D level of <15 ng/mL, 77 experienced a hospitalization with an infection, and 287 experienced a hospitalization without an infection. In multivariable analyses, a serum 25(OH)D level of <15 ng/mL was associated with a higher risk of hospitalization with an infection (risk ratio = 2.8, 95% confidence interval: 1.3, 5.9, P < 0.01) but not of hospitalization without an infection (risk ratio = 1.4, 95% confidence interval: 0.9, 2.1, P = 0.1). In this study, we found an association between a serum 25(OH)D concentration of <15 ng/mL and a higher subsequent risk for hospitalization with an infection among Medicare beneficiaries. PMID- 27189330 TI - Performance of Disease Risk Score Matching in Nested Case-Control Studies: A Simulation Study. AB - In a case-control study, matching on a disease risk score (DRS), which includes many confounders, should theoretically result in greater precision than matching on only a few confounders; however, this has not been investigated. We simulated 1,000 hypothetical cohorts with a binary exposure, a time-to-event outcome, and 13 covariates. Each cohort comprised 2 subcohorts of 10,000 patients each: a historical subcohort and a concurrent subcohort. DRS were estimated in the historical subcohorts and applied to the concurrent subcohorts. Nested case control studies were conducted in the concurrent subcohorts using incidence density sampling with 2 strategies-matching on age and sex, with adjustment for additional confounders, and matching on DRS-followed by conditional logistic regression for 9 outcome-exposure incidence scenarios. In all scenarios, DRS matching yielded lower average standard errors and mean squared errors than did matching on age and sex. In 6 scenarios, DRS matching also resulted in greater empirical power. DRS matching resulted in less relative bias than did matching on age and sex at lower outcome incidences but more relative bias at higher incidences. Post-hoc analysis revealed that the effect of DRS model misspecification might be more pronounced at higher outcome incidences, resulting in higher relative bias. These results suggest that DRS matching might increase the statistical efficiency of case-control studies, particularly when the outcome is rare. PMID- 27189329 TI - Statins and Risk of Bleeding: An Analysis to Evaluate Possible Bias Due to Prevalent Users and Healthy User Aspects. AB - Statins are said to protect against a wide range of diseases. We studied to what extent potential bias influences the results of studies on beneficial side effects of statins. We selected 8,188 atrial fibrillation patients who started treatment with anticoagulants at the Leiden Anticoagulation Clinic in the Netherlands between 2003 and 2009 and experienced 1,683 minor and 451 major bleeds during 18,105 person-years of follow-up. Statins were associated with a risk reduction of 9% for bleeds (hazard ratio = 0.91, 95% confidence interval: 0.82, 1.00). Additionally, analyses were stratified by age, incident users (patients who started statins during follow-up, i.e., an inception cohort), and prevalent statin users (statin users at baseline), as restriction to incident users avoids overoptimistic risk estimates. After stratification, the protective associations disappeared or reversed (range of hazard ratios = 0.99-3.22), except for patients aged 75 years or older. This remaining association could be due to another bias as, according to guidelines, in the elderly, statins should be prescribed only to those with a reasonable life expectancy. This could have resulted in a comparison of fit statin users with less fit nonstatin users (healthy user effect). The apparent protective association of statins on bleeds may be due to bias. We recommend stratification by age and incident and prevalent statin use when studying associations of statins with disease outcomes to avoid overoptimistic risk estimates. PMID- 27189335 TI - Efficient analysis of a small number of cancer cells at the single-cell level using an electroactive double-well array. AB - Analysis of the intracellular materials of a small number of cancer cells at the single-cell level is important to improve our understanding of cellular heterogeneity in rare cells. To analyze an extremely small number of cancer cells (less than hundreds of cells), an efficient system is required in order to analyze target cells with minimal sample loss. Here, we present a novel approach utilizing an advanced electroactive double-well array (EdWA) for on-chip analysis of a small number of cancer cells at the single-cell level with minimal loss of target cells. The EdWA consisted of cell-sized trap-wells for deterministic single-cell trapping using dielectrophoresis and high aspect ratio reaction-wells for confining the cell lysates extracted by lysing trapped single cells via electroporation. We demonstrated a highly efficient single-cell arraying (a cell capture efficiency of 96 +/- 3%) by trapping diluted human prostate cancer cells (PC3 cells). On-chip single-cell analysis was performed by measuring the intracellular beta-galactosidase (beta-gal) activity after lysing the trapped single cells inside a tightly enclosed EdWA in the presence of a fluorogenic enzyme substrate. The PC3 cells showed large cell-to-cell variations in beta-gal activity although they were cultured under the same conditions in a culture dish. This simple and effective system has great potential for high throughput single cell analysis of rare cells. PMID- 27189336 TI - The utility of indocyanine green fluorescence imaging during robotic adrenalectomy. AB - BACKGROUND AND OBJECTIVES: Indocyanine green (ICG) has been used for medical imaging since 1950s, but has more recently become available for use in minimally invasive surgery owing to improvements in technology. This study investigates the use of ICG florescence to guide an accurate dissection by delineating the borders of adrenal tumors during robotic adrenalectomy (RA). METHODS: This prospective study compared conventional robotic view with ICG fluorescence imaging in 40 consecutive patients undergoing RA. Independent, non-blinded observers assessed how accurately ICG fluorescence delineated the borders of adrenal tumors compared to conventional robotic view. RESULTS: A total of 40 patients underwent 43 adrenalectomies. ICG imaging was superior, equivalent, or inferior to conventional robotic view in 46.5% (n = 20), 25.6% (n = 11), and 27.9% (n = 12) of the procedures. On univariate analysis, the only parameter that predicted the superiority of ICG imaging over conventional robotic view was the tumor type, with adrenocortical tumors being delineated more accurately on ICG imaging compared to conventional robotic view. CONCLUSIONS: This study demonstrates the utility of ICG to guide the dissection and removal of adrenal tumors during RA. A simple reproducible method is reported, with a detailed description of the utility based on tumor type, approach and side. J. Surg. Oncol. 2016;114:153-156. (c) 2016 Wiley Periodicals, Inc. PMID- 27189337 TI - Three-dimensional compared to two-dimensional transesophageal echocardiography for diagnosis of infective endocarditis. AB - PURPOSE: Transesophageal echocardiography is crucial for the diagnosis of infective endocarditis (IE). Use of three-dimensional transesophageal echocardiography (3D-TEE) could improve the reliability of echocardiographic findings. This study sought to determine the value of 3D-TEE in the diagnosis of IE in comparison to two-dimensional (2D)-TEE and 2D transthoracic echocardiography (2D-TTE). METHODS: In this prospective cohort study in a tertiary care university hospital 144 consecutive patients with clinically suspected IE were included. The patients were subjected to clinical, microbiological and echocardiographic evaluation (2D-TTE, 2D-TEE and 3D-TEE) and their clinical history evaluated retrospectively to establish a reference diagnosis of IE in accordance to current guideline recommendations. RESULTS: In 48 (33 %) patients the diagnosis of IE was established. 2D-TEE and 3D-TEE showed a sensitivity, specificity, positive and negative predictive value for diagnosis of IE of 94 % and 63, 90 and 95 %, 82 and 86 % and 97 and 83 %, respectively, with similar results in patients with native and prosthetic valves. Vegetations and abscess were detected in 43 and 5 patients with final diagnosis of IE by any of the assessed echocardiographic modalities, with only one case of vegetation detected by 3D-TEE only and not by 2D-TEE. CONCLUSIONS: In this cohort of patients with suspected IE, 3D-TEE showed substantial lower sensitivity and negative predictive value for diagnosis of IE when compared to 2D-TEE. 3D-TEE might provide additive diagnostic information with impact on clinical decisions only in individual cases. PMID- 27189339 TI - Monitoring of Potential Safety Events and Vital Signs during Active Mobilization of Patients Undergoing Continuous Renal Replacement Therapy in a Medical Intensive Care Unit. AB - BACKGROUND/AIMS: This study aims to evaluate potential safety events and vital sign changes during active mobilization physical therapy (PT) in critically ill patients undergoing continuous renal replacement therapy (CRRT). METHODS: A retrospective review was performed on 29 patients who were treated with CRRT and who underwent 81 PT sessions in a medical intensive care unit at a single referral hospital; 15 patients underwent 33 sessions with passive range of motion (PROM) and 17 patients underwent 48 active mobilization PT sessions. Three patients received both types of PT including 8 PROM and 5 active mobilization PT sessions. The occurrences of safety events and vital sign changes during active mobilization PT sessions were evaluated. RESULTS: The safety events did not develop during 33 sessions with PROM. However, there were 2 safety events (4.1%) during 48 active mobilization PT sessions including one session with mobilization in the bed and the other in a sitting position on the edge of the bed. These safety events exclusively developed during active mobilization PT sessions, in which concomitant extracorporeal membrane oxygenation (ECMO) support and CRRT were delivered. Regarding vital sign changes during PT sessions, there were no significant differences in systolic blood pressure (BP), diastolic BP, mean arterial pressure, heart rate, respiratory rate, or peripheral oxygen saturation before and after both PROM and active mobilization PT sessions. CONCLUSIONS: This study showed that active mobilization PT can be performed safely in patients who are being treated with CRRT without a significant hemodynamic change. However, the development of potential safety events in patients with ECMO needs to be monitored carefully. PMID- 27189338 TI - In vitro and in vivo activity of EDTA and antibacterial agents against the biofilm of mucoid Pseudomonas aeruginosa. AB - PURPOSE: Refractory infection caused by bacterial biofilm is an important clinical problem. Pseudomonas aeruginosa is a common pathogen responsible for persistent and chronic biofilm infections. We aimed to explore the in vitro and in vivo activity of ethylenediamine tetraacetic acid (EDTA) in combination with antibacterial agents against mucoid P. aeruginosa biofilm. METHODS: The minimal inhibitory concentration (MIC) and minimal bactericidal concentration of ciprofloxacin, gentamicin, and ampicillin alone or with EDTA against P. aeruginosa were determined in vitro. Extracellular polysaccharides (EPS) and structural parameters of the biofilm were monitored. P. aeruginosa was aerosolized and delivered into the lungs of guinea pigs, which were treated with ciprofloxacin with or without EDTA. The colony-forming units (CFUs) of P. aeruginosa were determined from the lungs. RESULTS: EDTA reduced the MIC of ciprofloxacin and ampicillin by about 30-fold and that of gentamicin by twofold. EDTA reduced the biofilm EPS and the proportion of viable bacteria. The thickness, average diffusion distance, and textural entropy of EDTA-treated biofilm were significantly decreased. EDTA plus antibiotics reduced the colony counting from 107 to 103 CFU/mL. In vivo, EDTA plus ciprofloxacin had a significantly lower mean CFU/g of lung tissue (EDTA + ciprofloxacin 1.3 +/- 0.19; EDTA 4.4 +/- 0.57; ciprofloxacin 4.2 +/- 0.47), and lung lesions were less severe compared with the single treatment groups. CONCLUSIONS: EDTA can destroy the biofilm structures of mucoid P. aeruginosa in vitro. Moreover, EDTA and ciprofloxacin had a significant bactericidal effect against biofilm in vivo. PMID- 27189340 TI - Whole-transcriptome analysis of UUO mouse model of renal fibrosis reveals new molecular players in kidney diseases. AB - Transcriptome analysis by RNA-seq technology allows novel insights into gene expression and regulatory networks in health and disease. To better understand the molecular basis of renal fibrosis, we performed RNA-seq analysis in the Unilateral Ureteric Obstruction (UUO) mouse model. We analysed sham operated, 2- and 8-day post-ligation renal tissues. Thousands of genes with statistical significant changes in their expression were identified and classified into cellular processes and molecular pathways. Many novel protein-coding genes were identified, including critical transcription factors with important regulatory roles in other tissues and diseases. Emphasis was placed on long non-coding RNAs (lncRNAs), a class of molecular regulators of multiple and diverse cellular functions. Selected lncRNA genes were further studied and their transcriptional activity was confirmed. For three of them, their transcripts were also examined in other mouse models of nephropathies and their up- or down-regulation was found similar to the UUO model. In vitro experiments confirmed that one selected lncRNA is independent of TGFbeta or IL1b stimulation but can influence the expression of fibrosis-related proteins and the cellular phenotype. These data provide new information about the involvement of protein-coding and lncRNA genes in nephropathies, which can become novel diagnostic and therapeutic targets in the near future. PMID- 27189341 TI - MicroRNAs associated with increased AKT gene number in human lung carcinoma. AB - MicroRNA (miRNA) expression profiles were examined in 3 groups of lung carcinomas that had been stratified by increases in AKT1 or AKT2 gene number. Microarray analysis using 2000 probes revealed 87 miRNAs that were up-regulated and 32 down regulated miRNAs in carcinomas harboring amplification or high-level polysomy of the AKT1 (AKT1+), as well as 123 up-regulated and 83 down-regulated miRNAs in those of the AKT2 genes (AKT2+), in comparison with carcinomas harboring disomy of both (AKTd/d). In total, 182 miRNAs were up-regulated in AKT1+ or AKT2+, compared with AKTd/d. Among these, 28 miRNAs were up-regulated in both the AKT1+ and AKT2+ groups, with a log2 ratio between 1.02 and 3.71 relative to AKTd/d group, including all miR-200 family members. Quantitative real-time polymerase chain reaction showed that carcinomas exhibiting lymph vessel invasion had significantly lower expression of miR-200a (P=.0230) and miR-200b (P=.0168), regardless of the status of the AKT genes. Moreover, a detailed statistical analysis revealed that, in adenocarcinoma and in the early stage of carcinomas (pathologic stage I/II), expression of miR-200a was higher in the AKT2+ group compared with the AKT1+ group, and these differences were statistically significant (P=.0334 and P=.0239, respectively). However, the expression of miR 200a was not significantly correlated with the expression of its target, the zinc finger E-box-binding homeobox 1 (ZEB1; P=.3801) or E-cadherin (P=.2840), a marker of the epithelial-mesenchymal transition. These results suggest that AKT2 can regulate miR-200a in a histology- or stage-specific manner and that this regulation is independent of subsequent involvement of miR-200a in epithelial mesenchymal transition. PMID- 27189344 TI - Coexisting pituicytoma and pituitary adenoma: a second coincidence? PMID- 27189343 TI - Quantitative fibrosis estimation by image analysis predicts development of decompensation, composite events and defines event-free survival in chronic hepatitis B patients. AB - The extent of fibrosis is a major determinant of the clinical outcome in patients with chronic liver diseases. We undertook this study to explore the degree of fibrosis in baseline liver biopsies to predict clinical outcomes in chronic hepatitis B (CHB) patients. Fibrosis quantification was done by image analysis on Masson's trichrome-stained sections and correlated with clinical and biochemical parameters, liver stiffness and hepatic vein pressure gradient (n = 96). Follow up information collected related to clinical outcome. A total of 964 cases was analyzed. Median quantitative fibrosis (QF) was 3.7% (interquartile range, 1.6% 9.7%) with substantial variation in various stages. Median QF was F0, 1% (0.7% 1.65%); F1, 3.03% (2.07%-4.0%); F2, 7.1% (5.6%-8.7%); F3, 12.7% (10.15%-16.7%); F4, 26.9% (20.3%-36.4%). QF positively correlated with METAVIR staging, liver stiffness measurement, and hepatic vein pressure gradient. Eighty-nine cases developed liver-related events: decompensation, hepatocellular carcinoma, liver transplantation and death. Cox regression analysis after adjusting for METAVIR staging-QF, albumin, and AST for composite events; QF and albumin for decompensation; and only QF for hepatocellular carcinoma-were found to be significant predictors of clinical outcomes. QF categorized into five stages: QF1, 0%-5%; QF2, 5.1%-10%; QF3, 10.1%-15%; QF4, 15.1%-20%; QF5, >20.1%. In patients with advanced stages of QF, probability of event-free survival found to be low. Quantitative fibrosis in baseline liver biopsy predicts progression of the disease and disease outcome in CHB patients. QF defines the probability of event-free survival in CHB cases. PMID- 27189342 TI - ERG and PTEN status of isolated high-grade PIN occurring in cystoprostatectomy specimens without invasive prostatic adenocarcinoma. AB - High-grade prostatic intraepithelial neoplasia (HGPIN) is widely believed to represent a precursor to invasive prostatic adenocarcinoma. However, recent molecular studies have suggested that retrograde spread of invasive adenocarcinoma into pre-existing prostatic ducts can morphologically mimic HGPIN. Thus, previous molecular studies characterizing morphologically identified HGPIN occurring in radical prostatectomies or needle biopsies with concurrent invasive carcinoma may be partially confounded by intraductal spread of invasive tumor. To assess ERG and PTEN status in HGPIN foci likely to represent true precursor lesions in the prostate, we studied isolated HGPIN occurring without associated invasive adenocarcinoma in cystoprostatectomies performed at Johns Hopkins between 2009 and 2014. Of 344 cystoprostatectomies, 33% (115/344) contained invasive prostatic adenocarcinoma in the partially submitted prostate (10 blocks/case on average) and were excluded from the study. Of the remaining cases without sampled cancer, 32% (73/229) showed 133 separate foci of HGPIN and were immunostained for ERG and PTEN using genetically validated protocols. Of foci of HGPIN with evaluable staining, 7% (8/107) were positive for ERG. PTEN loss was not seen in any HGPIN lesion (0/88). Because these isolated HGPIN foci at cystoprostatectomy are unlikely to represent retrograde spread of invasive tumor, our study suggests that ERG rearrangement, but not PTEN loss, is present in a minority of potential neoplastic precursor lesions in the prostate. PMID- 27189345 TI - Non-genomic oestrogen receptor signal in B lymphocytes: An approach towards therapeutic interventions for infection, autoimmunity and cancer. AB - The non-genomic membrane bound oestrogen receptor (mER) regulates intracellular signals through receptor-ligand interactions. The mER, along with G-protein coupled oestrogen receptor GPR 30 (GPER), induces diverse cell signalling pathways in murine lymphocytes. The mER isoform ER-alpha46 has recently been demonstrated in human B and T lymphocytes as an analogue receptor for chemokine CCL18, the signalling events of which are not clearly understood. Ligand-induced mER and GPER signalling events are shared with BCR, CD19 mediated intracellular signalling through phospholipase C, PIP2/IP3/PI3 mediated activation of Akt, MAP kinase, and mTOR. Oestrogen has the ability to induce CD40-mediated activation of B cells. The complete signalling pathways of mER, GPR30 and their interaction with other signals are targeted areas for novel drug development in B cells during infection, autoimmunity and cancer. Therefore, an in depth investigation is critical for determining shared signal outputs during B cell activation. Here, we focus on the mode of action of membrane bound ER in B cells as therapeutic checkpoints. PMID- 27189347 TI - Corrigendum: Mutation analysis of the phospholamban gene in 315 South Africans with dilated, hypertrophic, peripartum and arrhythmogenic right ventricular cardiomyopathies. PMID- 27189346 TI - Pauci Immune crescentic glomerulonephritis in a patient with T-cell lymphoma and argyria. AB - BACKGROUND: Silver is a transition metal, toxic when ingested in significant amounts, causing argyria (skin deposition) and argyrosis (eye deposition). It is excreted mainly via the gastrointestinal tract with only small amounts eliminated by the kidneys, and rarely have cases of nephrotoxicity due to silver been reported. Here we present the case of a woman who used colloidal silver as an alternative remedy for a T cell lymphoma, who subsequently developed argyria and a pauci-immune crescentic glomerulonephritis with evidence of extensive glomerular basement membrane silver deposition. CASE PRESENTATION: A 47 year old woman of Indo-Asian descent with a T-cell lymphoma who refused conventional chemotherapy for 18 months but self-medicated with a remedy containing colloidal silver, was admitted with acute dialysis-dependent kidney injury. A kidney biopsy demonstrated a pauci-immune crescentic glomerulonephritis with deposition of silver particles in the mesangium and along the glomerular basement membranes. The patient was treated with intravenous methylprednisolone and intravenous cyclophosphamide and recovered independent renal function. CONCLUSION: Chronological evolution of the the pauci-immune glomerulonephritis suggests that a cellular immune-mediated process was induced, potentially mediated by lymphomatous T cells directed at the glomerular basement membrane, following silver deposition. Immunosuppressive therapy improved the situation and allowed cessation of haemodialysis, supporting the hypothesis of an immune-mediated process. PMID- 27189349 TI - Antagonism of Endothelin (ETA and ETB) Receptors During Renovascular Hypertension Induced Vascular Dementia Improves Cognition. AB - BACKGROUND: Diseases of cardio, as well as the cerebrovascular system, are known as the primary possibility for deficits in cognitive processes and dementia of vascular nature. Endothelin-1 (ET-1) and its receptors are extensively expressed in brain. OBJECTIVE: The present study has been structured to explore the effects of bosentan, an ET-1 antagonist on two-kidneyone- clip: 2K1C method induced hypertension provoked vascular dementia (VaD). METHOD: 2K1C was modelled to induce renovascular hypertension. Mean arterial blood pressure (MABP) was assessed using BIOPAC system. Cognitive impairment was assessed employing Elevated plus maze-EPM as well as Morris water maze-MWM. Brain cholinergic dysfunction (activity of acetylcholinesterase-AChE), oxidative stress (thiobarbituric acid reactive substances-TBARS level, glutathione-GSH content, superoxide dismutase-SOD as well as catalase-CAT activity), aortic oxidative stress (superoxide anion level), serum nitrosative stress (nitrite/nitrate level), brain inflammation (myeloperoxidase-MPO), vascular endothelial dysfunction (endothelium-dependent relaxation) and infarct size (2,3,5- triphenyltetrazolium chloride-TTC staining) were assessed. RESULTS: Renal artery ligated animals have shown elevated oxidative stress in the aorta (superoxide anion-SA) and brain (augmented TBARS, with decreased GSH, SOD, and CAT). Similarly, 2K1C-renovascular hypertension has shown a considerable rise in brain inflammation (MPO activity) and brain AChE activity with a significant fall in serum nitrite/ nitrate contents. Administration of bosentan considerably diminished 2K1C hypertension induced alterations in MABP, cognitive impairment, and dysfunction of endothelium. Treatment with bosentan has also restored 2K1C induced a rise in brain TBARS, AChE, MPO activity, reduction in brain GSH, SOD and CAT as well as brain damage. CONCLUSION: It may be concluded that ET-1 antagonism may be regarded as possible agents for managing renovascular hypertension induced VaD. PMID- 27189348 TI - A platform for actively loading cargo RNA to elucidate limiting steps in EV mediated delivery. AB - Extracellular vesicles (EVs) mediate intercellular communication through transfer of RNA and protein between cells. Thus, understanding how cargo molecules are loaded and delivered by EVs is of central importance for elucidating the biological roles of EVs and developing EV-based therapeutics. While some motifs modulating the loading of biomolecular cargo into EVs have been elucidated, the general rules governing cargo loading and delivery remain poorly understood. To investigate how general biophysical properties impact loading and delivery of RNA by EVs, we developed a platform for actively loading engineered cargo RNAs into EVs. In our system, the MS2 bacteriophage coat protein was fused to EV-associated proteins, and the cognate MS2 stem loop was engineered into cargo RNAs. Using this Targeted and Modular EV Loading (TAMEL) approach, we identified a configuration that substantially enhanced cargo RNA loading (up to 6-fold) into EVs. When applied to vesicles expressing the vesicular stomatitis virus glycoprotein (VSVG) - gesicles - we observed a 40-fold enrichment in cargo RNA loading. While active loading of mRNA-length (>1.5 kb) cargo molecules was possible, active loading was much more efficient for smaller (~0.5 kb) RNA molecules. We next leveraged the TAMEL platform to elucidate the limiting steps in EV-mediated delivery of mRNA and protein to prostate cancer cells, as a model system. Overall, most cargo was rapidly degraded in recipient cells, despite high EV-loading efficiencies and substantial EV uptake by recipient cells. While gesicles were efficiently internalized via a VSVG-mediated mechanism, most cargo molecules were rapidly degraded. Thus, in this model system, inefficient endosomal fusion or escape likely represents a limiting barrier to EV-mediated transfer. Altogether, the TAMEL platform enabled a comparative analysis elucidating a key opportunity for enhancing EV-mediated delivery to prostate cancer cells, and this technology should be of general utility for investigations and applications of EV-mediated transfer in other systems. PMID- 27189350 TI - Correction: Discovery of a (19)F MRI sensitive salinomycin derivative with high cytotoxicity towards cancer cells. AB - Correction for 'Discovery of a (19)F MRI sensitive salinomycin derivative with high cytotoxicity towards cancer cells' by Qiuyan Shi et al., Chem. Commun., 2016, 52, 5136-5139. PMID- 27189351 TI - Mycobacterium paraintracellulare sp. nov., for the genotype INT-1 of Mycobacterium intracellulare. AB - Three mycobacterial strains, isolated from independent Korean patients with pulmonary infections, belonging to the Mycobacterium intracellulare genotype 1 (INT-1) were characterized using a polyphasic approach. The sequences of the 16S rRNA gene and internal transcribed spacer 1 (ITS1) of the INT-1 strains were identical to those of Mycobacterium intracellulare ATCC 13950T. However, multilocus sequence typing (MLST) analysis targeting five housekeeping genes (hsp65, rpoB, argG, gnd and pgm) revealed the phylogenetic separation of these strains from M. intracellulare ATCC 13950T. DNA-DNA hybridization values of >70 % confirmed that the three isolates belong to the same species, while the values of <70 % between one of them and the type strains of M. intracellulare and Mycobacterium chimaera confirmed their belonging to a distinct species. In addition, phenotypic characteristics such as positive growth on MacConkey agar and in acidic broth culture, unique matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS profiles of lipids, and unique mycolic acids profiles further supported the taxonomic status of these strains as representatives of a novel species of the Mycobacterium avium complex named Mycobacterium paraintracellulare. The type strain is MOTT64T (=KCTC 29084T=JCM 30622T). PMID- 27189353 TI - Does Obesity Influence on the Functional Outcomes of a Total Knee Arthroplasty? AB - BACKGROUND: The objective of this study was to compare the total knee arthroplasty (TKA) functional outcomes and quality of life of obese and non-obese patients. METHODS: Prospective comparative study, including all patients underwent TKA in a single centre. Patients were divided into three groups: Group 1 (Gr.1) BMI <30 kg/m2, Group 2 (Gr.2) BMI >= 30 kg/m2 and <35 kg/m2 and Group 3 (Gr.3) BMI >=35 kg/m2. The Knee Society score (KSS) and SF-36 scores were obtained preoperatively and at 5 years of follow-up. RESULTS: A total of 689 patients were included (72.2 +/- 7 years, 76.3 % women). Overall, pre- and post operative values of SF-36 were lower for the obese group. However the improvement obtained in the three groups was similar in all the sub-scales of the SF-36 score. KSS values were higher in the non-obese group in both periods. However the improvement obtained in this score in the three groups was similar (Gr.1; 70.21 +/- 34.31, Gr.2; 66.53 +/- 34.93, Gr.3; 60.94 +/- 38.47, n.s.). CONCLUSIONS: Although non-obese patients obtained better functional and reported quality of life scores than obese patients, there were no differences in the gain of quality of life and knee functionality between both groups at 5-years of follow-up. This is one of the largest series in a single centre published in literature and confirms the results obtained by other authors. Taking into account the different outcomes obtained, surgery should not be denied to patients that are obese, given that they obtained similar benefit than non-obese patients. PMID- 27189354 TI - The Diabetes Surgery Summit II Guidelines: a Disease-Based Clinical Recommendation. AB - There is mounting evidence, derived from mechanistic studies, RCTs, and other high-quality studies that there are weight loss independent antidiabetic effects of gastrointestinal surgery. Additionally, there appears to be no relation between the positive metabolic outcomes to baseline BMI. The outdated US National Health Institutes guidelines from 1991 were centered on BMI only criterion and often misleading. The Second Diabetes Surgery Summit held in collaboration with leading diabetes organizations and endorsed by a large group of international Professional Societies developed guidelines that defined eligibility based on the severity and degree of T2D medical control while referring to obesity as a qualifier and not the sole criterion. That is the first time that guidelines are provided to put metabolic surgery into the T2D treatment algorithms. PMID- 27189352 TI - Rate of Death and Complications in Laparoscopic and Open Roux-en-Y Gastric Bypass. A Meta-analysis and Meta-regression Analysis on 69,494 Patients. AB - Morbid obesity is a life threatening condition. Currently, surgery represents the only effective and durable therapeutic option to treat it. The first aim of the study was to estimate and compare the major surgical complications and the 30-day rate of mortality between laparoscopic and open Roux-en-Y gastric bypass (LRYGB and RYGB). The second aim was to evaluate the change in outcomes, complications, and deaths, with increased experience over the time period of the review. A random effect of the meta-analysis and meta-regression was used to evaluate surgical complications (i.e., reoperation, stenosis, bleeding, surgical site infection, fistula, internal hernia, and incisional ventral hernia) and the rate of mortality after LRYGB and RYGB over time. A search of literature from 2000 to 2014 led to the selection of 17 papers. When looking at surgical techniques separately, we observed a higher rate of mortality for open surgery (death rate 0.82 %, 95 % CI = 0.49-1.23) compared to laparoscopic surgery (death rate 0.22 %, 95 % CI = 0.09-0.40). This difference resulted highly significant when the two techniques were formally compared (p < 0.001). The improving of surgery technique resulted in a mean rate of mortality reduction of 0.069 %. Laparoscopy represents the approach of choice for bariatric surgery. Contemporary reports of LRYGB show low mortality rates and progressive decline in postoperative complications. Laparoscopic bariatric surgery requires advanced laparoscopic skills, and probably an extended learning curve is not accounted for by current mortality statistics. PMID- 27189355 TI - Predictive Accuracy of Violence Risk Scale-Sexual Offender Version Risk and Change Scores in Treated Canadian Aboriginal and Non-Aboriginal Sexual Offenders. AB - The present study examined the predictive properties of Violence Risk Scale Sexual Offender version (VRS-SO) risk and change scores among Aboriginal and non Aboriginal sexual offenders in a combined sample of 1,063 Canadian federally incarcerated men. All men participated in sexual offender treatment programming through the Correctional Service of Canada (CSC) at sites across its five regions. The Static-99R was also examined for comparison purposes. In total, 393 of the men were identified as Aboriginal (i.e., First Nations, Metis, Circumpolar) while 670 were non-Aboriginal and primarily White. Aboriginal men scored significantly higher on the Static-99R and VRS-SO and had higher rates of sexual and violent recidivism; however, there were no significant differences between Aboriginal and non-Aboriginal groups on treatment change with both groups demonstrating close to a half-standard deviation of change pre and post treatment. VRS-SO risk and change scores significantly predicted sexual and violent recidivism over fixed 5- and 10-year follow-ups for both racial/ancestral groups. Cox regression survival analyses also demonstrated positive treatment changes to be significantly associated with reductions in sexual and violent recidivism among Aboriginal and non-Aboriginal men after controlling baseline risk. A series of follow-up Cox regression analyses demonstrated that risk and change score information accounted for much of the observed differences between Aboriginal and non-Aboriginal men in rates of sexual recidivism; however, marked group differences persisted in rates of general violent recidivism even after controlling for these covariates. The results support the predictive properties of VRS-SO risk and change scores with treated Canadian Aboriginal sexual offenders. PMID- 27189356 TI - Patient Navigation As a Model to Increase Participation of African Americans in Cancer Clinical Trials. AB - PURPOSE: Less than 10% of patients enrolled in clinical trials are minorities. The patient navigation model has been used to improve access to medical care but has not been evaluated as a tool to increase the participation of minorities in clinical trials. The Increasing Minority Participation in Clinical Trials project used patient navigators (PNs) to enhance the recruitment of African Americans for and their retention in therapeutic cancer clinical trials in a National Cancer Institute-designated comprehensive cancer center. METHODS: Lay individuals were hired and trained to serve as PNs for clinical trials. African American patients potentially eligible for clinical trials were identified through chart review or referrals by clinic nurses, physicians, and social workers. PNs provided two levels of services: education about clinical trials and tailored support for patients who enrolled in clinical trials. RESULTS: Between 2007 and 2014, 424 African American patients with cancer were referred to the Increasing Minority Participation in Clinical Trials project. Of those eligible for a clinical trial (N = 378), 304 (80.4%) enrolled in a trial and 272 (72%) consented to receive patient navigation support. Of those receiving patient navigation support, 74.5% completed the trial, compared with 37.5% of those not receiving patient navigation support. The difference in retention rates between the two groups was statistically significant (P < .001). Participation of African Americans in therapeutic cancer clinical trials increased from 9% to 16%. CONCLUSION: Patient navigation for clinical trials successfully retained African Americans in therapeutic trials compared with non-patient navigation trial participation. The model holds promise as a strategy to reduce disparities in cancer clinical trial participation. Future studies should evaluate it with racial/ethnic minorities across cancer centers. PMID- 27189357 TI - Assessing Colorectal Cancer Screening Adherence of Medicare Fee-for-Service Beneficiaries Age 76 to 95 Years. AB - INTRODUCTION: There are concerns about potential overuse of colorectal cancer (CRC) screening services among average-risk individuals older than age 75 years. MATERIALS AND METHODS: Using a 5% random noncancer sample of Medicare beneficiaries who resided in the SEER areas, we examined rates of CRC screening adherence, defined by the Medicare coverage policy, among average-risk fee-for service beneficiaries age 76 to 95 years from 2002 to 2010. The two outcomes are the status of overall CRC screening adherence, and the status of adherence to colonoscopy (v other modalities) conditional on patient adherence. RESULTS: Overall CRC screening adherence rates of Medicare beneficiaries age 76 to 95 years increased from 13.0% to 21.4% from 2002 to 2010. In 2002, 2.2% of beneficiaries were adherent to colonoscopy, and 10.7%, by other modalities; the corresponding rates were 19.5% and 1.9%, respectively, in 2010. Specifically, rates of adherence to colonoscopy were 1.1% for those age 86 to 90 years and almost nil for those age 91 to 95 years in 2002, but the rates became 13.5% and 8.2%, respectively, in 2010. Compared with white beneficiaries, black beneficiaries age 76 to 95 years had a 7-percentage-point lower adherence rate. However, overall adherence rates among blacks increased by 168.6% from 2002 to 2010, whereas rates among whites increased by 63.0%. Logistic regressions showed that blacks age 86 to 95 years were less likely than whites to be adherent (odds ratio, 0.56; 95% CI, 0.47 to 0.59) but were more likely to be adherent to colonoscopy (odds ratio, 2.34; 95% CI, 1.47 to 3.91). CONCLUSION: High proportions of average-risk Medicare fee-for-service beneficiaries screened by colonoscopy may represent opportunities for improving appropriateness and allocative efficiency of CRC screening by Medicare. PMID- 27189359 TI - Unexpected Increases in Fecundity of Ceriodaphnia dubia Exposed to Reused Rice Irrigation Water. AB - Steady increases in agricultural irrigation raise concerns about environmental impacts. Rice producing regions face declining irrigation groundwater and have started reusing irrigation water as a substitute. The goal of this project was to determine if reused irrigation water is potentially toxic compared to conventional well irrigation water. Reused and well water samples, collected from three Arkansas rice farms at field inlets and outlets on three dates corresponding to fertilizer/chemical applications or crop management, were used in acute 48-h (Pimephales promelas) and chronic (Ceriodaphnia dubia) toxicity evaluations. Acute toxicity tests indicated no effects on P. promelas. Fecundity of C. dubia was significantly increased in the reused water inlet and in both the reused and well water rice field outlets compared to well water inlets and laboratory reference water. This study suggests that, compared to well water, reused rice irrigation water has reduced potential for significant negative environmental impact on biota in receiving waters. PMID- 27189358 TI - Genetic and Hematologic Endpoints in Astyanax altiparanae (Characidae) After Exposure and Recovery to Water-Soluble Fraction of Gasoline (WSFG). AB - The sublethal effects of water-soluble fraction of gasoline (WSFG, 1.5 % v/v) were evaluated in the freshwater fish, Astynax altiparanae, after acute exposure (96 h) under a semi-static system. In addition, the recovery process was assessed in the fish following contaminant depuration. Recovery treatments were carried out with gradual depuration (GD), consisting of 7 days in the WSFG, followed by 8 days in clean water; and treatments with total depuration in clean water for 15 (DEP 15) and 30 days (DEP 30). The effects were evaluated through the piscine micronucleus test and by differential counting of organic defense cells. Acute exposure increased the frequency of neutrophils. In the GD treatment, the thrombocyte count and erythrocytic nuclear abnormalities (ENA) increased. In the DEP 15 treatment, there was a reduction of ENA; and following 30 days of depuration (i.e., DEP 30), the number of lymphocytes increased and the thrombocyte count remained high. These results indicate a long-term response to a condition of stress from WSFG. PMID- 27189360 TI - The Pichia pastoris transmembrane protein GT1 is a glycerol transporter and relieves the repression of glycerol on AOX1 expression. AB - Promoter of alcohol oxidase I (PAOX1) is the most efficient promoter involved in the regulation of recombinant protein expression in Pichia pastoris (P. pastoris). PAOX1 is tightly repressed by the presence of glycerol in the culture medium; thus, glycerol must be exhausted before methanol can be taken up by P. pastoris and the expression of the heterologous protein can be induced. In this study, a candidate glycerol transporter (GT1, GeneID: 8197545) was identified, and its role was confirmed by further studies (e.g. bioinformatics analysis, heterologous complementation in Schizosaccharomyces pombe (S. pombe)). When GT1 is co-expressed with enhanced green fluorescent protein (EGFP), it localizes to the membrane and S. pombe carrying gt1 but not the wild-type strain can grow on medium containing glycerol as the sole carbon source. The present study is the first to report that AOX1 in the X-33Deltagt1 mutant can achieve constitutive expression in medium containing glycerol; thus, knocking down gt1 can eliminate the glycerol repression of PAOX1 in P. pastoris These results suggest that the glycerol transporter may participate in the process of PAOX1 inhibition in glycerol medium. PMID- 27189361 TI - Genetic and phenotypic characterization of Saccharomyces spp. strains isolated in distillery plants. AB - In this study, the biodiversity and some interesting phenotypic properties of Saccharomyces wild yeasts isolated in distilleries, at least 100 years old, located in La Mancha (Spain), were determined. Strains were genetically characterized by RFLP-mtDNA, which confirmed a great genetic biodiversity with 73% of strains with different mtDNA profiles, highlighting the large variability found in sweet and fermented piquette substrata. The predominant species identified was S. cerevisiae, followed by S. paradoxus and S. bayanus Due to the residual sugar-alcohol extraction process using warm water, a great number of thermophilic Saccharomyces strains with a great cell vitality were found to have potential use as starters in distillery plants. Interesting technological properties such as cell vitality and growth rate at different temperatures were studied. The thermal washing process for the extraction of alcohol and reducing sugars of some raw materials contributes to the presence of Saccharomyces strains with technologically interesting properties, especially in terms of vitality and resistance to high temperatures. Due to the fact that fermentation is spontaneous, the yeast biota of these environments, Saccharomyces and non Saccharomyces, is very varied so these ecological niches are microbial reserves of undoubted biotechnological interest. PMID- 27189362 TI - Trehalose-6-phosphate synthesis controls yeast gluconeogenesis downstream and independent of SNF1. AB - Trehalose-6-P (T6P), an intermediate of trehalose biosynthesis, was identified as an important regulator of yeast sugar metabolism and signaling. tps1Delta mutants, deficient in T6P synthesis (TPS), are unable to grow on rapidly fermentable medium with uncontrolled influx in glycolysis, depletion of ATP and accumulation of sugar phosphates. However, the exact molecular mechanisms involved are not fully understood. We show that SNF1 deletion restores the tps1Delta growth defect on glucose, suggesting that lack of TPS hampers inactivation of SNF1 or SNF1-regulated processes. In addition to alternative, non fermentable carbon metabolism, SNF1 controls two major processes: respiration and gluconeogenesis. The tps1Delta defect appears to be specifically associated with deficient inhibition of gluconeogenesis, indicating more downstream effects. Consistently, Snf1 dephosphorylation and inactivation on glucose medium are not affected, as confirmed with an in vivo Snf1 activity reporter. Detailed analysis shows that gluconeogenic Pck1 and Fbp1 expression, protein levels and activity are not repressed upon glucose addition to tps1Delta cells, suggesting a link between the metabolic defect and persistent gluconeogenesis. While SNF1 is essential for induction of gluconeogenesis, T6P/TPS is required for inactivation of gluconeogenesis in the presence of glucose, downstream and independent of SNF1 activity and the Cat8 and Sip4 transcription factors. PMID- 27189363 TI - Complete genome sequence and transcriptome regulation of the pentose utilizing yeast Sugiyamaella lignohabitans. AB - Efficient conversion of hexoses and pentoses into value-added chemicals represents one core step for establishing economically feasible biorefineries from lignocellulosic material. While extensive research efforts have recently provided advances in the overall process performance, the quest for new microbial cell factories and novel enzymes sources is still open. As demonstrated recently the yeast Sugiyamaella lignohabitans (formerly Candida lignohabitans) represents a promising microbial cell factory for the production of organic acids from lignocellulosic hydrolysates. We report here the de novo genome assembly of S. lignohabitans using the Single Molecule Real-Time platform, with gene prediction refined by using RNA-seq. The sequencing revealed a 15.98 Mb genome, subdivided into four chromosomes. By phylogenetic analysis, Blastobotrys (Arxula) adeninivorans and Yarrowia lipolytica were found to be close relatives of S. lignohabitans Differential gene expression was evaluated in typical growth conditions on glucose and xylose and allowed a first insight into the transcriptional response of S. lignohabitans to different carbon sources and different oxygenation conditions. Novel sequences for enzymes and transporters involved in the central carbon metabolism, and therefore of potential biotechnological interest, were identified. These data open the way for a better understanding of the metabolism of S. lignohabitans and provide resources for further metabolic engineering. PMID- 27189364 TI - Three Candida albicans potassium uptake systems differ in their ability to provide Saccharomyces cerevisiae trk1trk2 mutants with necessary potassium. AB - Yeasts usually have one or two high-affinity potassium transporters. Two complete and one interrupted gene encoding three types of putative potassium uptake system exist in Candida albicans SC5314. As high intracellular potassium is essential for many yeast cell functions, the existence of three transporters with differing transport mechanisms (Trk uniporter, Hak cation-proton symporter, Acu ATPase) may help pathogenic C. albicans cells to acquire the necessary potassium in various organs and tissues of the host. When expressed in Saccharomyces cerevisiae lacking their own potassium uptake systems, all three putative transporters were able to provide cells with the ability to grow with low amounts of potassium over a broad range of external pH. Only CaTrk1 was properly recognized and secreted to the plasma membrane. Nevertheless, even the small number of CaHak1 and mainly CaAcu1 molecules which reached the plasma membrane resulted in an improved growth of cells in low potassium concentrations, suggesting a high affinity and capacity of the transporters. A single-point mutation restored the complete CaACU1 gene, and the resulting protein not only provided cells with the necessary potassium but also improved their tolerance to toxic lithium. In contrast to its known homologues, CaAcu1 did not seem to transport sodium. PMID- 27189365 TI - Ian Dawes-the third Pope-lucky to be a researcher. AB - Retrospective articles are an excuse for a rosy tinted view of one's life. This fully expurgated version is no exception. No "what the butler saw" or the vilification of enemies that one finds in political autobiographies - merely the account of one born to a generation of those whose forebears never had the chance to go to university and enjoy the subsequent fruits of that education - and of one who by chance stumbled into the world of yeast genetics and molecular biology, who had a lot of fun on the way and who never sought to leave it. PMID- 27189367 TI - Yeast peroxisomes: structure, functions and biotechnological opportunities. AB - Peroxisomes are ubiquitous organelles found in most eukaryotic cells. In yeasts, peroxisomes play important roles in cell metabolism, especially in different catabolic processes including fatty acid beta-oxidation, the glyoxylic shunt and methanol metabolism, as well as some biosynthetic processes. In addition, peroxisomes are the compartment in which oxidases and catalase are localized. New peroxisomes mainly arise by fission of pre-existing ones, although they can also be formed from the endoplasmic reticulum (ER). Peroxisomes consist of matrix soluble proteins and membrane proteins known as peroxins. A total of 34 PEX peroxin genes and proteins have been identified to date. and their functions have been elucidated. Protein import into peroxisomes depends on peroxins and requires specific signals in the structure of transported proteins: PTS1, PTS2 and mPTS. The mechanisms of metabolite penetration into peroxisomes are still poorly understood. Peroxisome number and the volume occupied by these organelles are tightly regulated. Methanol, fatty acids and methylamine act as efficient peroxisome proliferators, whereas glucose and ethanol induce peroxisome autophagic degradation (pexophagy). To date, 42 Atg proteins involved in pexophagy are known. Catabolism and alcoholic fermentation of the major pentose sugar, xylose, depend on peroxisomal enzymes. Overexpression of peroxisomal transketolase and transaldolase activates xylose fermentation. Peroxisomes could be useful as target organelles for overexpression of foreign toxic proteins. PMID- 27189366 TI - Mutations of charged amino acids at the cytoplasmic end of transmembrane helix 2 affect transport activity of the budding yeast multidrug resistance protein Pdr5p. AB - Pdr5p is a major ATP-binding cassette (ABC) transporter in Saccharomyces cerevisiae. It displays a sequence and functional homology to the pathogenic Candida albicans multidrug resistance protein Cdr1p. The transmembrane helices of Pdr5p act in substrate recognition, binding, translocation and eventual removal of toxic substances out of the plasma membrane via the formation of a binding pocket. In this study, we identify two novel Pdr5 mutants (E574K and E580K), which exhibit impaired substrate efflux functions. Both mutants remained hypersensitive to all tested Pdr5p substrates without affecting their protein expression levels, localization or ATPase activities. As E574 and E580 are both located adjacent to the predicted cytoplasmic end of transmembrane helix 2, this implies that such charged residues are functionally essential for Pdr5p. Molecular docking studies suggest the possibility that oppositely charged substitution at residue E574 may disturb the interaction between the substrates and Pdr5p, resulting in impaired transport activity. Our results present new evidence, suggesting that transmembrane helix 2 plays an important role for the efflux function of Pdr5p. PMID- 27189368 TI - The GCA1 gene encodes a glycosidase-like protein in the cell wall of Candida albicans. AB - Candida albicans Gca1p is a putative glucoamylase enzyme which contains 946 amino acids, 11 putative sites for N-glycosylation and 9 for O-glycosylation. Gca1p was identified in beta-mercaptoethanol extracts from isolated cell walls of strain C. albicans SC5314 and it is involved in carbohydrate metabolism. The significance and the role of this protein within the cell wall structure were studied in the corresponding mutants. The homozygous mutant showed that GCA1 was not an essential gene for cell viability. Subsequent phenotypic analysis performed in the mutants obtained did not show significant difference in the behavior of mutant when compared with the wild strain SC5314. Zymoliase, Calcofluor White, Congo red, SDS, caffeine or inorganic compounds did not affect the integrity of the cell wall. No differences were observed when hyphal formation assays were carried out. However, an enzyme assay in the presence of substrate p-nitrophenyl alpha-D-glucopyranoside enabled us to detect a significant decrease in glycosidase activity in the mutants compared with the parental strain, revealing the function of Gca1. PMID- 27189369 TI - Kluyveromyces lactis genome harbours a functional linker histone encoding gene. AB - Linker histones are essential components of chromatin in eukaryotes. Through interactions with linker DNA and nucleosomes they facilitate folding and maintenance of higher-order chromatin structures and thus delicately modulate gene activity. The necessity of linker histones in lower eukaryotes appears controversial and dubious. Genomic data have shown that Schizosaccharomyces pombe does not possess genes encoding linker histones while Kluyveromyces lactis has been reported to have a pseudogene. Regarding this controversy, we have provided the first direct experimental evidence for the existence of a functional linker histone gene, KlLH1, in K. lactis genome. Sequencing of KlLH1 from both genomic DNA and copy DNA confirmed the presence of an intact open reading frame. Transcription and splicing of the KlLH1 sequence as well as translation of its mRNA have been studied. In silico analysis revealed homology of KlLH1p to the histone H1/H5 protein family with predicted three domain structure characteristic for the linker histones of higher eukaryotes. This strongly proves that the yeast K. lactis does indeed possess a functional linker histone gene thus entailing the evolutionary preservation and significance of linker histones. The nucleotide sequences of KlLH1 are deposited in the GenBank under accession numbers KT826576, KT826577 and KT826578. PMID- 27189370 TI - Methylation-mediated downregulation of long noncoding RNA LOC100130476 in gastric cardia adenocarcinoma. AB - Accumulating evidences indicate that long non-coding RNAs (lncRNAs) play important roles in several biological processes and dysregulated lncRNAs are involved in different kinds of cancer and are associated with carcinogenesis, metastasis, and prognosis of cancer. The role of a new lncRNA LOC100130476 in gastric cardia adenocarcinoma (GCA) has remained unknown. The present study investigated the role and methylation status of LOC100130476 in the pathogenesis of GCA, and further evaluated the potential prognostic role of LOC100130476 in GCA. Significant downregulation of LOC100130476 was detected in SGC-7901 and BGC 823 cell lines and primary GCA tissues. Methylation frequency of LOC100130476 was gradually increased from exon 1 to exon 2 both in tumor tissues and corresponding normal tissues; however, methylation status of region 1 closing to the transcription start site was more tumor-specific among the three regions examined. The findings of the association between LOC100130476 expression, methylation and TNM stage, pathological differentiation, and GCA patients' survival further identified the role of LOC100130476 as a tumor suppressor gene. Furthermore, the hypermethylation of LOC100130476 was also detected in peripheral white blood cells of GCA cases. Thus, LOC100130476 may be act as a tumor suppressor gene in GCA carcinogenesis and aberrant methylation at the CpG sites near the transcription start site within exon 1 may be critical for gene silencing. In addition, aberrant methylation of LOC100130476 in peripheral white blood cells and GCA tissues may be used as a potential valuable biomarker in GCA diagnosis and prognosis. PMID- 27189373 TI - Prevalence of Anxiety and Depression in Pulmonary Hypertension and Changes during Therapy. AB - BACKGROUND: Pulmonary hypertension (PH) leads to reduced health-related quality of life (HRQoL). OBJECTIVE: To investigate the prevalence and course of anxiety and depression and their association with HRQoL, disease severity and survival in PH. METHODS: 131 PH patients (91 pulmonary arterial, 30 chronic thromboembolic, 10 due to lung disease; 84 female, 47 male) had repeated assessments with the Hospital Anxiety and Depression Scale (HADS), HRQoL, six-minute walk distance and WHO functional class during a mean course of 16 +/- 12 months. RESULTS: Among the 49 incident and 82 prevalent PH patients, the HADS score was positive in 53%/21% (depression), 51%/24% (anxiety) and 63%/26% (total score) (all p < 0.05). The HADS score was improved at the second assessment in incident patients. The HADS score correlated with HRQoL at all consecutive assessments and with functional class until the third assessment, but not with baseline hemodynamics, age or gender. CONCLUSION: Mood disorders remain underdiagnosed in PH. The higher prevalence of anxiety/depression in incident versus prevalent patients and the improvement over time may indicate an amelioration of mood disorders after PH diagnosis and treatment. PMID- 27189372 TI - Seasonal immunoregulation in a naturally-occurring vertebrate. AB - BACKGROUND: Fishes show seasonal patterns of immunity, but such phenomena are imperfectly understood in vertebrates generally, even in humans and mice. As these seasonal patterns may link to infectious disease risk and individual condition, the nature of their control has real practical implications. Here we characterize seasonal dynamics in the expression of conserved vertebrate immunity genes in a naturally-occurring piscine model, the three-spined stickleback. RESULTS: We made genome-wide measurements (RNAseq) of whole-fish mRNA pools (n = 36) at the end of summer and winter in contrasting habitats (riverine and lacustrine) and focussed on common trends to filter habitat-specific from overarching temporal responses. We corroborated this analysis with targeted year round whole-fish gene expression (Q-PCR) studies in a different year (n = 478). We also considered seasonal tissue-specific expression (6 tissues) (n = 15) at a third contrasting (euryhaline) locality by Q-PCR, further validating the generality of the patterns seen in whole fish analyses. Extremes of season were the dominant predictor of immune expression (compared to sex, ontogeny or habitat). Signatures of adaptive immunity were elevated in late summer. In contrast, late winter was accompanied by signatures of innate immunity (including IL-1 signalling and non-classical complement activity) and modulated toll-like receptor signalling. Negative regulators of T-cell activity were prominent amongst winter-biased genes, suggesting that adaptive immunity is actively down regulated during winter rather than passively tracking ambient temperature. Network analyses identified a small set of immune genes that might lie close to a regulatory axis. These genes acted as hubs linking summer-biased adaptive pathways, winter-biased innate pathways and other organismal processes, including growth, metabolic dynamics and responses to stress and temperature. Seasonal change was most pronounced in the gill, which contains a considerable concentration of T-cell activity in the stickleback. CONCLUSIONS: Our results suggest major and predictable seasonal re-adjustments of immunity. Further consideration should be given to the effects of such responses in seasonally occurring disease. PMID- 27189374 TI - Comparison of the compact dry TC method with the standard method ISO 21149:2006 for determining aerobic colony counts in cosmetic emulsion. AB - OBJECTIVE: Compact Dry TC, a rapid method kit for determining aerobic colony counts, has been developed by Nissui Pharmaceutical Co. for food application. These plates are pre-sterilized and contain culture medium, a cold-soluble gelling agent and a colour redox indicator for rapid enumeration. In this study, the alternative method is compared with the standard method ISO 21149:2006 - Cosmetic - Microbiology - Enumeration and detection of aerobic mesophilic bacteria, for cosmetic emulsions application. METHODS: An oil-in-water (o/w) cosmetic emulsion was contaminated with a pool of bacterial strains (Escherichia coli ATCC 8739, Staphylococcus aureus ATCC 6538 and Pseudomonas aeruginosa ATCC 9027). One millilitre of samples was spread on agar as described in ISO 21149. The colonies were enumerated after 3 days of incubation. At the same time, 1.2 mL samples were spread on Compact Dry TC kits. The kit was incubated at 35 degrees C +/- 1 degrees C for 48 h, and the colonies were enumerated. Accuracy determination was carried out using six replicates at four levels of concentrations (10, 50, 100 and 250 CFU mL-1 ). The repeatability study was carried out using 12 replicates at four levels of concentrations (10, 50, 100 and 250 CFU mL-1 ). Variations relative to the analyst and to the batch of emulsion have been investigated. RESULTS: The linear correlation coefficients of Compact Dry TC Kit enumeration with standard method ISO 21149:2006 was 0.9999. In comparison study, no apparent differences were noted between the Compact Dry TC kit and the reference method ISO 21149, for the detection level of aerobic microorganisms. Relative accuracy, repeatability and intermediate precision studies were acceptable. In the repeatability study, the Shapiro-Wilk test has confirmed the normally distribution of the twelve assays. No significant variations in Compact Dry TC count results were observed with different analysts and different batches of emulsion. CONCLUSION: The results showed that the two compared methods 'Compact Dry TC' vs. 'conventional pour plate' performed equally well. Demonstration was achieved that the Compact Dry TC method may constitute a useful alternative tool for rapid enumeration of aerobic mesophilic bacteria in cosmetic emulsions. PMID- 27189375 TI - "Alarm-corrected" ergonomic armrest use could improve learning curves of novices on robotic simulator. AB - BACKGROUND: In robotic surgery, the professional ergonomic habit of using an armrest reduces operator fatigue and increases the precision of motion. We designed and validated a pressure surveillance system (PSS) based on force sensors to investigate armrest use. The objective was to evaluate whether adding an alarm to the PSS system could shorten ergonomic training and improve performance. STUDY DESIGN: Twenty robot and simulator-naive participants were recruited and randomized in two groups (A and B). The PSS was installed on a robotic simulator, the dV-Trainer, to detect contact with the armrest. The Group A members completed three tasks on the dV-Trainer without the alarm, making 15 attempts at each task. The Group B members practiced the first two tasks with the alarm and then completed the final tasks without the alarm. The simulator provided an overall score reflecting the trainees' performance. We used the new concept of an "armrest load" score to describe the ergonomic habit of using the armrest. RESULTS: Group B had a significantly higher performance score (p < 0.001) and armrest load score (p < 0.001) than Group A from the fifth attempt of the first task to the end of the experiment. CONCLUSIONS: Based on the conditioned reflex effect, the alarm associated with the PSS rectified ergonomic errors and accelerated professional ergonomic habit acquisition. The combination of the PSS and alarm is effective in significantly shortening the learning curve in the robotic training process. PMID- 27189376 TI - Extramedullary Involvement of the Sigmoid Colon with Acute Lymphocytic Leukemia. PMID- 27189371 TI - Minimal residual disease in breast cancer: an overview of circulating and disseminated tumour cells. AB - Within the field of cancer research, focus on the study of minimal residual disease (MRD) in the context of carcinoma has grown exponentially over the past several years. MRD encompasses circulating tumour cells (CTCs)-cancer cells on the move via the circulatory or lymphatic system, disseminated tumour cells (DTCs)-cancer cells which have escaped into a distant site (most studies have focused on bone marrow), and resistant cancer cells surviving therapy-be they local or distant, all of which may ultimately give rise to local relapse or overt metastasis. Initial studies simply recorded the presence and number of CTCs and DTCs; however recent advances are allowing assessment of the relationship between their persistence, patient prognosis and the biological properties of MRD, leading to a better understanding of the metastatic process. Technological developments for the isolation and analysis of circulating and disseminated tumour cells continue to emerge, creating new opportunities to monitor disease progression and perhaps alter disease outcome. This review outlines our knowledge to date on both measurement and categorisation of MRD in the form of CTCs and DTCs with respect to how this relates to cancer outcomes, and the hurdles and future of research into both CTCs and DTCs. PMID- 27189377 TI - Association of serum leptin and adiponectin with anthropomorphic indices of obesity, blood lipids and insulin resistance in a Sub-Saharan African population. AB - BACKGROUND: There is little data on the metabolic effects of adipokines in sub Saharan African populations. This study aimed to explore the potential relationship of leptin and adiponectin, with obesity, plasma lipids and insulin resistance in a Cameroonian population. METHODS: We enrolled 167 men and 309 women aged >=18 years from the general population in Cameroon. Data were collected on waist circumference (WC), body mass index (BMI), waist-to-hip ratio (WHR), body fat (BF%), fasting blood glucose, plasma lipids, adiponectin, leptin, insulin and homeostasis model for assessment of insulin resistance (HOMA-IR). Pearson's correlation and multiple stepwise linear regression analyses were used to determine correlates of leptin and adiponectin serum levels. RESULTS: The prevalence of obesity was higher in women compared to men (p < 0.0001), and Central obesity which is more prevalent particularly in women (WC = 42.4%, WHR = 42.3%), is almost for 90% comparable to %BF (42.7%). Adiponectin negatively with BMI (r = -0.294, p < 0.0001), WC (r = -0.294, p < 0.0001), %BF (r = -0.122, p = 0.028), WHR (r = -0.143, p = 0.009), triglycerides (r = -0.141, p = 0.011), HOMA IR (r = -0.145, p = 0.027) and insulin (r = -0.130, p = 0.048). Leptin positively correlated with BMI (r = 0.628), WC (r = 0.530), BF% (r = 0.720), (all p < 0.0001); with DBP (r = 0.112, p = 0.043), total cholesterol (r = 0.324, p < 0.0001), LDL-cholesterol (r = 0.298, p < 0.0001), insulin (r = 0.320, p < 0.001 and HOMA-IR (r = 0.272, p < 0.0001). In multiple stepwise regression analysis, adiponectin was negatively associated with WC (beta = -0.38, p = 0.001) and BF% (beta = 0.33, p < 0.0001), while leptin was positively associated with BF% (beta = 0.60, p < 0.0001), total cholesterol (beta = 0.11, p = 0.02) and HOMA-IR (beta = 0.11, p = 0.02). When controlled for gender, HOMA-IR was found significantly associated to adiponectin (beta = 0.13, p = 0.046), but not BF%, while the association previously found between leptin and HOMA-IR disappeared; BMI and WC were significantly associated with leptin (beta = 0.18, p = 0.04 & beta = 0.19, p = 0.02 respectively). CONCLUSION: This study, which includes a population who was not receiving potentially confounding medications, confirms the associations previously observed of adiponectin with reduced adiposity especially central adiposity and improved insulin sensitivity. Confirmatory associations were also observed between leptin and obesity, blood lipids and insulin resistance for the first time in an African population. Gender was significant covariate interacting with insulin sensitivity/insulin resistance and obesity indexes associations in this population. PMID- 27189379 TI - The HPA axis and ethanol: a synthesis of mathematical modelling and experimental observations. AB - Stress and alcohol use are interrelated-stress contributes to the initiation and upholding of alcohol use and alcohol use alters the way we perceive and respond to stress. Intricate mechanisms through which ethanol alters the organism's response to stress remain elusive. We have developed a stoichiometric network model to succinctly describe neurochemical transformations underlying the stress response axis and use numerical simulations to model ethanol effects on complex daily changes of blood levels of cholesterol, 6 peptide and 8 steroid hormones. Modelling suggests that ethanol alters the dynamical regulation of hypothalamic pituitary-adrenal (HPA) axis activity by affecting the amplitude of ultradian oscillations of HPA axis hormones, which defines the threshold with respect to which the response to stress is being set. These effects are complex-low/moderate acute ethanol challenge (<8 mM) may reduce, leave unaltered or increase the amplitude of ultradian cortisol (CORT) oscillations, giving rise to an intricate response at the organism level, offering also a potential explanation as to why apparently discordant results were observed in experimental studies. In contrast, high-dose acute ethanol challenge (>8 mM) increases instantaneous CORT levels and the amplitude of ultradian CORT oscillations in a dose-dependent manner, affecting the HPA axis activity also during the following day(s). Chronic exposure to ethanol qualitatively changes the HPA axis dynamics, whereas ethanol at intoxicating levels shuts down this dynamic regulation mechanism. Mathematical modelling gives a quantitative biology-based framework that can be used for predicting how the integral HPA axis response is perturbed by alcohol. PMID- 27189380 TI - Multispectroscopic and Isotopic Ratio Analysis To Characterize the Inorganic Binder Used on Pompeian Pink and Purple Lake Pigments. AB - Because of the fact that pigments are not ubiquitous in the archeological record, the application of noninvasive analytical methods is a necessity. In this work, pink and purple lake pigments recovered from the excavations of the ancient city of Pompeii (Campania, Italy) and preserved in their original bowls at the Naples National Archaeological Museum (Italy) were analyzed to characterize the composition of their inorganic binders (mordants). In situ preliminary analyses using a hand-held energy dispersive X-ray fluorescence spectrometer (HH-ED-XRF) allowed us to determine the use of an aluminosilicate enriched in Cu and Pb. Scanning electron microscopy coupled to energy dispersive X-ray spectrometry (SEM EDS) and benchtop ED-XRF analyses confirmed these results, while inductively coupled plasma mass spectrometry (ICPMS) allowed one to determine the concentration of major, minor, and trace elements. The use of other techniques such as X-ray diffraction (XRD), and micro-Raman and infrared spectroscopies allowed one to characterize the pigments at the molecular level. The high concentration of Cu detected in the pigments (1228-12937 MUg g(-1)) could be related to the addition of Cu salts to obtain the desired final hue. The concentrations of Pb (987-2083 MUg g(-1)) was also remarkable. Lead isotopic ratio analysis ((206)Pb/(207)Pb) suggested a possible origin related to the leaching of the ancient lead pipes from Pompeii and the subsequent transfer to the buried pigments or to the inorganic binder. Molecular analysis also showed that the binder is composed of an allophane-like clay. Moreover, it was possible to determine that to obtain the final purple hue of a specific pigment, Pompeian blue pigment was also mixed into the dyed clay. PMID- 27189378 TI - Hyper IgM Syndrome: a Report from the USIDNET Registry. AB - PURPOSE: The United States Immunodeficiency Network (USIDNET) patient registry was used to characterize the presentation, genetics, phenotypes, and treatment of patients with Hyper IgM Syndrome (HIGM). METHODS: The USIDNET Registry was queried for HIGM patient data collected from October 1992 to July 2015. Data fields included demographics, criteria for diagnosis, pedigree analysis, mutations, clinical features, treatment and transplant records, laboratory findings, and mortality. RESULTS: Fifty-two physicians entered data from 145 patients of ages 2 months to 62 years (median 12 years); 131 were males. Using patients' age at last entry, data from 2072 patient years are included. Mutations were recorded for 85 subjects; 82 were in CD40LG. Eighteen subjects had non-X linked HIGM. 40 % had a normal serum IgM and 15 %, normal IgA. Infections were reported for 91 %, with pulmonary, ear, and sinus infections being the most common. 42 % had Pneumocystis jirovecii pneumonia; 6 % had Cryptosporidium. 41 % had neutropenia. 78 % experienced non-infectious complications: chronic diarrhea (n = 22), aphthous ulcers (n = 28), and neoplasms (n = 8) including colon cancer, adrenal adenoma, liver adenocarcinoma, pancreatic carcinoid, acute myeloid leukemia, hepatoma, and, in a female with an autosomal dominant gain of function mutation in PIK3CD, an ovarian dysgerminoma. Thirteen patients had a hematopoietic marrow or stem cell transplant; three had solid organ transplants. Thirteen were known to have died (median age = 14 years). CONCLUSIONS: Analysis of the USIDNET Registry provides data on the common clinical features of this rare syndrome, and in contrast with previously published data, demonstrates longer survival times and reduced gastrointestinal manifestations. PMID- 27189382 TI - Sweetening yoghurt with glucose, but not with saccharin, promotes weight gain and increased fat pad mass in rats. AB - The claim that non-nutritive sweeteners accelerate body weight gain by disrupting sweet-calorie associations was tested in two experiments using rats. The experiments were modelled on a key study from a series of experiments reporting greater body weight gain in rats fed yoghurt sweetened with saccharin than with glucose (Swithers & Davidson, 2008). Both of the current experiments likewise compared groups fed saccharin- or glucose-sweetened yoghurt in addition to chow and water, while Experiment 1 included a third group (Control) given unsweetened yoghurt. In Experiment 1, but not in Experiment 2, rats were initially exposed to both saccharin- and glucose-sweetened yoghurts to assess their relative palatability. We also tested whether the provision of an energy-dense sweet biscuit would augment any effects of saccharin on food intake and weight gain, as seemingly predicted by Swithers and Davidson (2008). In Experiment 1 there were no differences in body weight gain or fat pad mass between the Saccharin and Control group, whereas the Glucose group was the heaviest by the final 5 weeks and at cull had the largest fat pads. Greater acceptance of saccharin predicted more weight gain over the whole experiment. Consistent with past reports, fasting blood glucose and insulin measures did not differ between the Saccharin and Control groups, but suggested some impairment of insulin sensitivity in the Glucose group. Experiment 2 found similar effects of glucose on fat mass, but not on body weight gain. In summary, adding saccharin had no detectable effects on body-weight regulation, whereas the effects of glucose on fat pad mass were consistent with previous studies reporting more harmful effects of sugars compared to non-nutritive sweeteners. PMID- 27189381 TI - The use of complementary and alternative medicine by 7427 Australian women with cyclic perimenstrual pain and discomfort: a cross-sectional study. AB - BACKGROUND: To assess the prevalence of cyclic perimenstrual pain and discomfort and to detail the pattern of complementary and alternative (CAM) use adopted by women for the treatment of these symptoms. METHODS: Data from the 2012 national Australian Longitudinal Study of Women's Health (ALSWH) cross-sectional survey of 7427 women aged 34-39 years were analysed to estimate the prevalence of endometriosis, premenstrual syndrome (PMS), irregular or heavy periods and severe dysmenorrhoea and to examine the association between their symptoms and their visits to CAM practitioners as well as their use of CAM therapies and products in the previous 12 months. RESULTS: The prevalence of endometriosis was 3.7 % and of the perimenstrual symptoms assessed, PMS was most prevalent at 41.2 % whilst irregular bleeding (22.2 %), heavy periods (29.8 %) and severe period pain (24.1 %) were reported at lower levels. Women with endometriosis were more likely than non-sufferers to have consulted with a massage therapist or acupuncturist and to have used vitamins/minerals, yoga/meditation or Chinese medicines (p < 0.05). PMS sufferers were more likely to consult with an osteopath, massage therapist, naturopath/herbalist or alternative health practitioner and to have used all forms of CAM therapies except Chinese medicines than women who had infrequent PMS (all p < 0.05). Women with irregular periods did not have different patterns of CAM use from non-sufferers and those with heavy periods did not favour any form of CAM but were less likely to visit a massage therapist or use yoga/meditation than non-sufferers (p < 0.05). For women with severe dysmenorrhoea there was no difference in their visits to CAM practitioners compared to non-sufferers but they were more likely to use aromatherapy oils (p < 0.05) and for more frequent dysmenorrhoea also herbal medicines, Chinese medicines and other alternative therapies compared to non-sufferers (all p < 0.05). CONCLUSIONS: There is a high prevalence of cyclic perimenstrual pain and discomfort amongst women in this age group. Women were using CAM differentially when they had specific symptoms of cyclic perimenstrual pain and discomfort. The use of CAM needs to be properly assessed to ensure their safe, effective use and to ascertain their significance as a treatment option enabling women with menstrual problems and their care providers to improve their quality of life. PMID- 27189383 TI - A qualitative study exploring visible components of organizational culture: what influences the use of psychotropic medicines in nursing homes? AB - BACKGROUND: The influence of organizational culture on how psychotropic medicines are used in nursing homes has not been extensively studied. Schein's theory provides a framework for examining organizational culture which begins with the exploration of visible components of an organization such as behaviors, structures, and processes. This study aimed to identify key visible components related to the use of psychotropic medicines in nursing homes. METHODS: A qualitative study was conducted in eight nursing homes in Sydney, Australia. Purposive sampling was used to conduct semi-structured interviews with 40 participants representing a broad range of health disciplines. Thematic analysis was used to derive concepts. RESULTS: Three visible components were related to psychotropic medicine use. These were drugs and therapeutics committee meetings, pharmacist led medication management reviews and formal and informal meetings with residents and their families. We found that only a few nursing homes utilized drugs and therapeutics committee meetings to address the overuse of psychotropic medicines. Pharmacist led medication management reviews provided a lever to minimize inappropriate psychotropic prescribing for a number of nursing homes; however, in others it was used as a box-ticking exercise. We also found that some nursing homes used meetings with residents and their families to review the use of psychotropic medicines. CONCLUSION: This study was the first to illustrate that visible components of organizational culture do influence the use of psychotropic medicines and explains in detail what of the culture needs to be addressed to reduce inappropriate psychotropic prescribing. PMID- 27189385 TI - GP practices rated "outstanding" are better funded, BMA research finds. PMID- 27189384 TI - Childhood Pompe disease: clinical spectrum and genotype in 31 patients. AB - BACKGROUND: As little information is available on children with non-classic presentations of Pompe disease, we wished to gain knowledge of specific clinical characteristics and genotypes. We included all patients younger than 18 years, who had been evaluated at the Pompe Center in Rotterdam, the Netherlands, between 1975 and 2012, excluding those with the classic-infantile form. None were treated with enzyme replacement therapy at the time of evaluation. We collected information on first symptoms, diagnosis, use of a wheelchair and/or respirator, and enzyme and mutation analysis and assessed muscle strength, pulmonary function, and cardiac parameters. RESULTS: Thirty-one patients participated. Median age at symptom onset was 2.6 years (range 0.5-13y) and at diagnosis 4.0 years. Most first problems were delayed motor development and problems related to limb-girdle weakness. Fatigue, persistent diarrhea and problems in raising the head in supine position were other first complaints. Ten patients were asymptomatic at time of diagnosis. Five of them developed symptoms before inclusion in this study. Over 50 % of all patients had low or absent reflexes, a myopathic face, and scoliosis; 29 % were underweight. Muscle strength of the neck flexors, hip extensors, hip flexors, and shoulder abductors were most frequently reduced. Pulmonary function was decreased in over 48 % of the patients; 2 patients had cardiac hypertrophy. Patients with mutations other than the c.-32 13T > G were overall more severely affected, while 18 out of the 21 patients (86 %) with the c.-32-13T > G/'null' genotype were male. CONCLUSIONS: Our study shows that Pompe disease can present with severe mobility and respiratory problems during childhood. Pompe disease should be considered in the differential diagnosis of children with less familiar signs such as disproportional weakness of the neck flexors, unexplained fatigue, persistent diarrhea and unexplained high CK/ASAT/ALAT. Disease presentation appears to be different from adult patients. The majority of affected children with GAA genotype c.-32-13T > G/'null' appeared to be male. PMID- 27189387 TI - Open vs Laparoscopic Simple Prostatectomy: A Comparison of Initial Outcomes and Cost. AB - INTRODUCTION: We compared the cost-effectiveness of laparoscopic simple prostatectomy (LSP) vs open prostatectomy (OP). PATIENTS AND METHODS: A total of 73 men treated for benign prostatic hyperplasia were enrolled for OP and LSP in groups 1 and 2, respectively. The findings were recorded perioperative, including operation time (OT), blood lost, transfusion rate, conversion to the open surgery, and the complications according to the Clavien Classification. The postoperative findings, including catheterization and drainage time, the amount of analgesic used, hospitalization time, postoperative complications, international prostate symptom score (IPSS) and International Index of Erectile Function (IIEF) scores, the extracted prostate weight, the uroflowmeter, as well as postvoiding residual (PVR) and quality of life (QoL) score at the postoperative third month, were analyzed. The cost of both techniques was also compared statistically. RESULTS: No statistical differences were found in the preoperative parameters, including age, IPSS and QoL score, maximum flow rate (Qmax), PVR, IIEF score, and prostate volumes, as measured by transabdominal ultrasonography. No statistical differences were established in terms of the OT and the weight of the extracted prostate. No differences were established with regard to complications according to Clavien's classification in groups. However, the bleeding rate was significantly lower in group 2. The drainage, catheterization, and hospitalization times and the amount of analgesics were significantly lower in the second group. The postoperative third month findings were not different statistically. Only the Qmax values were significantly greater in group 2. While there was only a $52 difference between groups with regard to operation cost, this difference was significantly different. CONCLUSION: The use of LSP for the prostates over 80 g is more effective than the OP in terms of OT, bleeding amount, transfusion rates, catheterization time, drain removal time, hospitalization time, consumed analgesic amount, and Qmax values. On the other hand, the mean cost of the LSP is higher than OP. Better effectiveness comes with higher cost. PMID- 27189388 TI - Dutch homeless people 2.5 years after shelter admission: what are predictors of housing stability and housing satisfaction? AB - Housing stability is an important focus in research on homeless people. Although definitions of stable housing differ across studies, the perspective of homeless people themselves is generally not included. Therefore, this study explored the inclusion of satisfaction with the participant's current housing status as part of the definition of housing stability and also examined predictors of housing stability with and without the inclusion of homeless person's perspective. Of the initial cohort consisting of 513 homeless participants who were included at baseline in 2011, 324 (63.2%) were also interviewed at 2.5-year follow-up. To determine independent predictors of housing stability, we fitted multivariate logistic regression models using stepwise backward regression. At 2.5-year follow up, 222 participants (68.5%) were stably housed and 163 participants (51.1%) were stably housed and satisfied with their housing status. Having been arrested (OR = 0.36, 95% CI: 0.20-0.63), a high level of somatisation (physical manifestations of psychological distress) (OR = 0.52, 95% CI: 0.30-0.91) and having unmet care needs (OR = 0.77, 95% CI: 0.60-0.99) were negative predictors of housing stability. Having been arrested (OR = 0.43, 95% CI: 0.25-0.75), high debts (OR = 0.45, 95% CI: 0.24-0.84) and a high level of somatisation (OR = 0.49, 95% CI: 0.28-0.84) were negative predictors of stable housing when satisfaction with the housing status was included. Because inclusion of a subjective component revealed a subgroup of stably housed but not satisfied participants and changed the significant predictors, this seems a relevant addition to the customary definition of housing stability. Participants with characteristics negatively associated with housing stability should receive more extensive and individually tailored support services to facilitate achievement of housing stability. PMID- 27189386 TI - Hepatitis C Genotype Prevalence in Monastir Region, Tunisia: Correlation between 5' Untranslated Region (5'UTR), Non-structural 5B (NS5B), and Core Sequences in HCV Subtyping. AB - Hepatitis C virus (HCV) is a causative agent of chronic liver disease, cirrhosis, and hepatocellular carcinoma. It constitutes a major public health around the world. There is no vaccine available against HCV, and current therapies are effective in only small percentage of patients. HCV has wide population-specific genotype variability. Genotype knowledge and viral load assessment are equally important for designing therapeutic strategies. Taking into account that the molecular epidemiology of HCV variants circulating in Tunisia is not yet well elucidated, and that, at present, little is known about the distribution pattern of HCV in Monastir region (Tunisia), we aimed, herein, to evaluate the prevalence of HCV genotypes in Monastir and to identify risk-related factors. For this purpose, 50 anti-HCV antibody-positive cases were diagnosed and subjected to viral RNA extraction, amplification, genotyping, and viral load quantification. Molecular epidemiology was studied by 5' untranslated region (5' UTR) sequencing as compared with the non-structural 5B (NS5B) and core region sequences. Overall concordance between 5' UTR, core, and NS5B sequencing was 100 %. The highest prevalent genotype was 1b (50 %) followed by genotypes 1a (16 %), 4a (12 %), 2a (10 %), 2c (8 %), and 3a (4 %). Interestingly, the subtype 1b had a statistically significant higher viral load than the other genotypes followed by subtype 1a. Based on these data, this study revealed a high prevalence of HCV genotype 1 (subtypes 1b and 1a) compared to other genotypes. A continued monitoring of HCV and knowledge of circulating genotypes could impact on future vaccine formulations. PMID- 27189389 TI - No association between level of vitamin D and chronic low back pain in Swedish primary care: a cross-sectional case-control study. AB - OBJECTIVE: Assessment of vitamin D levels and deficiency status in individuals with chronic low back pain (CLBP) in a Swedish general population, compared with controls matched for sex and age. DESIGN: Cross-sectional case-control study. SETTING: Primary care, southern Sweden. SUBJECTS: Participants (n = 44) with self reported low back pain for at least 3 months and individually sex- and age matched controls without a chronic pain condition (n = 44), recruited from the general population by random letter of invitation. MAIN OUTCOME MEASURE: Association between vitamin D level and CLBP when adjusting for possible confounders in a multivariate forward conditional logistic regression model. RESULTS: Mean S-25-hydroxyvitamin D levels were 81 and 80 nmol/L in the CLBP and control group, respectively. The prevalence of vitamin D deficiency was low and similar in the CLBP group and the control group. Vitamin D level was not associated with CLBP when potential confounders were taken into account. CONCLUSIONS: No difference in vitamin D levels between participants with CLBP and matched controls could be demonstrated in the present sample. Assessment of vitamin D level and deficiency status may be of questionable value in the management of CLBP in primary care settings at similar latitudes, unless there are additional risk factors for deficiency or specific indicators of osteomalacia. Key points Vitamin D deficiency is common and reported in many chronic pain conditions, including chronic low back pain (CLBP), but evidence for an association and causality is insufficient. * The present study found no association between vitamin D levels and CLBP in a case-control sample of 44 + 44 individuals from the Swedish general population. * Prevalence of vitamin D deficiency was low and comparable in individuals with CLBP and controls without chronic pain, matched for sex and age. * Assessment of vitamin D status, for the purpose of finding and treating an underlying cause of pain, may be of limited value in the management of CLBP in primary care settings at similar latitudes. PMID- 27189390 TI - Metallosis with pseudotumour formation: Long-term complication following cementless total hip replacement in a dog. AB - CASE DESCRIPTION: A 10-year-old female Belgian Teruven dog was presented to our clinic for total hip revision following a diagnosis of implant (cup) failure with metallosis and abdominal pseudotumour formation. The patient had a cementless metal-on-polyethylene total hip replacement performed nine years prior to presentation. CLINICAL FINDINGS: The clinical findings, including pseudotumour formation locally and at sites distant from the implant and pain associated with the joint replacement, were similar to those described in human patients with this condition. Histopathological, surgical, and radiographic findings additionally supported the diagnosis of metallosis and pseudotumour formation. TREATMENT AND OUTCOME: Distant site pseudotumours were surgically removed and the total hip replacement was explanted due to poor bone quality. The patient recovered uneventfully and has since resumed normal activity. CONCLUSION: In veterinary patients with metal-on-polyethylene total hip implants, cup failure leading to metallosis and pseudotumour formation should be considered as a potential cause of ipsilateral hindlimb lameness, intra-pelvic abdominal tumours, or a combination of both. These clinical findings may occur years after total hip replacement surgery. PMID- 27189392 TI - The Ontogeny of Cultural Learning. AB - Developmental research has the potential to address some of the critical gaps in our scientific understanding of the role played by cultural learning in ontogenetic outcomes. The goal of this special section was to gather together leading examples of research on cultural learning across a variety of social contexts and caregiving settings. Although the field of developmental psychology continues to struggle with the persistent problem of oversampling U.S. and Western European populations, we argue that the articles in this special section add to the growing evidence that children everywhere draw on a repertoire of cultural learning strategies that optimize their acquisition of the specific practices, beliefs, and values of their communities. We also identify future directions and outline best practices for the conduct of research on cultural learning. PMID- 27189391 TI - Direct transfemoral transcatheter aortic valve implantation without balloon pre dilatation using the Edwards Sapien XT valve. AB - OBJECTIVES: To evaluate the feasibility and safety of direct transcatheter aortic valve implantation (TAVI) by the transfemoral approach without balloon pre dilatation using the Edwards SapienXT valve. BACKGROUND: TAVI is established in selected high-risk patients with severe aortic stenosis. Balloon aortic valvuloplasty (BAV) is recommended prior to valve implantation, but may contribute to procedural risk. It is unknown whether this is necessary for successful passage and deployment of the device. METHODS: 81 patients (mean age 84 [95%CI:82-85.8], 62% male, median EuroScore 22.8% [95%CI:20.5-27]) undergoing transfemoral TAVI (35 by direct implantation [direct group]; 46 with balloon pre dilatation [balloon group]) between 2010 and 2013 were analyzed for efficacy and safety endpoints. RESULTS: Procedural success was 100%. Pre and post-procedural peak gradients in the direct group were 66mmHg (95%CI:59-72.8) and 14mmHg (95%CI:12-17.8)(P < 0.0001) compared to 76.5mmHg (95%CI:73.7-94.0) and 17mmHg (95%CI:16-19)(P < 0.0001) in the balloon group. Post-dilatation was performed in 4/35(11.4%) of the direct group and 3/46(6.5%) of the balloon group (P = 0.83). Post procedure moderate AR was present in 1/35(2.9%) in the direct group and none in the balloon group. In-hospital mortality (2.9% direct vs. 0% balloon group), stroke (2.9% vs. 4.4%), tamponade (2.9% vs. 2.2%), major vascular complications (2.9% vs. 8.7%) and new permanent pacing (2.2% vs. 0) were similar. Pacing time, inflations, radiation dose and contrast use were all significantly lower in the direct group. CONCLUSIONS: Direct implantation of the Edwards SapienXT valve during TAVI by the transfemoral route appears safe, efficacious and feasible in those without extreme calcification. (c) 2016 Wiley Periodicals, Inc. PMID- 27189393 TI - Cultural Learning Redux. AB - M. Tomasello, A. Kruger, and H. Ratner (1993) proposed a theory of cultural learning comprising imitative learning, instructed learning, and collaborative learning. Empirical and theoretical advances in the past 20 years suggest modifications to the theory; for example, children do not just imitate but overimitate in order to identify and affiliate with others in their cultural group, children learn from pedagogy not just episodic facts but the generic structure of their cultural worlds, and children collaboratively co-construct with those in their culture normative rules for doing things. In all, human children do not just culturally learn useful instrumental activities and information, they conform to the normative expectations of the cultural group and even contribute themselves to the creation of such normative expectations. PMID- 27189394 TI - Playing With Knives: The Socialization of Self-Initiated Learners. AB - Since Margaret Mead's field studies in the South Pacific a century ago, there has been the tacit understanding that as culture varies, so too must the socialization of children to become competent culture users and bearers. More recently, the work of anthropologists has been mined to find broader patterns that may be common to childhood across a range of societies. One improbable commonality has been the tolerance, even encouragement, of toddler behavior that is patently risky, such as playing with or attempting to use a sharp-edged tool. This laissez faire approach to socialization follows from a reliance on children as "self-initiated learners." In this article, the ethnographic literature that shows why children are encouraged to learn without prompting or guidance and how that happens is reviewed. PMID- 27189395 TI - How Universal Are Free Will Beliefs? Cultural Differences in Chinese and U.S. 4- and 6-Year-Olds. AB - This study explores the development of free will beliefs across cultures. Sixty seven Chinese 4- and 6-year-olds were asked questions to gauge whether they believed that people could freely choose to inhibit or act against their desires. Responses were compared to those given by the U.S. children in Kushnir, Gopnik, Chernyak, Seiver, and Wellman (). Results indicate that children from both cultures increased the amount of choice they ascribed with age. For inhibition questions, Chinese children ascribed less choice than the U.S. children. Qualitative explanations revealed that the U.S. children were also more likely to endorse notions of autonomous choice. These findings suggest both cultural differences and similarities in free will beliefs. PMID- 27189396 TI - Taking Turns or Not? Children's Approach to Limited Resource Problems in Three Different Cultures. AB - Some problems of resource distribution can be solved on equal terms only by taking turns. We presented such a problem to 168 pairs of 5- to 10-year-old children from one Western and two non-Western societies (German, Samburu, Kikuyu). Almost all German pairs solved the problem by taking turns immediately, resulting in an equal distribution of resources throughout the game. In the other groups, one child usually monopolized the resource in Trial 1 and sometimes let the partner monopolize it in Trial 2, resulting in an equal distribution in only half the dyads. These results suggest that turn-taking is not a natural strategy uniformly across human cultures, but rather that different cultures use it to different degrees and in different contexts. PMID- 27189397 TI - Learning to Be Unsung Heroes: Development of Reputation Management in Two Cultures. AB - The effective management of one's reputation is an important social skill, but little is known about how it develops. This study seeks to bridge the gap by examining how children communicate about their own good deeds, among 7- to 11 year-olds in both China and Canada (total N = 378). Participants cleaned a teacher's messy office in her absence, and their responses were observed when the teacher returned. Only the Chinese children showed an age-related increase in modesty by choosing to falsely deny their own good deeds. This modest behavior was uniquely predicted by Chinese children's evaluations of modesty-related lies. The results suggest that culture-specific socialization processes influence the way children communicate with authority figures about prosocial deeds. PMID- 27189398 TI - Similarities and Differences in Maternal Responsiveness in Three Societies: Evidence From Fiji, Kenya, and the United States. AB - The first relationship between an infant and her caregiver, typically the mother, lays the foundation for cognitive, social, and emotional development. Maternal responsiveness and affect mirroring have been studied extensively in Western societies yet very few studies have systematically examined these caregiving features in non-Western settings. Sixty-six mother-infant dyads (7 months, SD = 3.1) were observed in a small-scale, rural island society in Fiji, a village in Kenya, and an urban center in the United States. Mothers responded similarly to infant bids overall, but differences were found across societies in the ways mothers selectively respond to affective displays. This has implications for understanding early emotion socialization as well as understanding variation in infant social ecologies across the globe. PMID- 27189399 TI - Reactions to Receiving a Gift-Maternal Scaffolding and Cultural Learning in Berlin and Delhi. AB - This study shows how Berlin (n = 35) and Delhi (n = 28) mothers scaffold a common and highly scripted social situation, namely gift giving, and enable cultural learning in 19-month-olds. Using modeling and prompting to encourage appropriate responses, mothers took culture-specific directions during scaffolding that were in line with the broader cultural model as assessed by maternal socialization goals (SGs). Whereas Berlin mothers prioritized autonomous SGs, Delhi mothers emphasized autonomous and relational SGs to similar degrees. During scaffolding, Berlin mothers focused on maximizing positive affect and acknowledging the gift, whereas Delhi mothers prompted toddlers to acknowledge the giver more often. Furthermore, there were differences in toddlers' behavior in line with these culture-specific scripts guiding gift giving. PMID- 27189400 TI - Learning From Others and Spontaneous Exploration: A Cross-Cultural Investigation. AB - How does early social experience affect children's inferences and exploration? Following prior work on children's reasoning in pedagogical contexts, this study examined U.S. children with less experience in formal schooling and Yucatec Mayan children whose early social input is predominantly observational. In Experiment 1, U.S. 2-year-olds (n = 77) showed more restricted exploration of a toy following a pedagogical demonstration than an interrupted, accidental, or no demonstration (baseline). In Experiment 2, Yucatec Mayan and U.S. 2-year-olds (n = 66) showed more restricted exploration following a pedagogical than an observational demonstration, while only Mayan children showed more restriction with age. These results suggest that although schooling is not a necessary precursor for sensitivity to pedagogy, early social experience may influence children's inferences and exploration in pedagogical contexts. PMID- 27189401 TI - Culture Influences Action Understanding in Infancy: Prediction of Actions Performed With Chopsticks and Spoons in Chinese and Swedish Infants. AB - The cultural specificity of action prediction was assessed in 8-month-old Chinese and Swedish infants. Infants were presented with an actor eating with a spoon or chopsticks. Predictive goal-directed gaze shifts were examined using eye tracking. The results demonstrate that Chinese infants only predict the goal of eating actions performed with chopsticks, whereas Swedish infants exclusively predict the goal of eating actions performed with a spoon. Infants in neither culture predicted the goal of object manipulation actions (e.g., picking up food) performed with a spoon or chopsticks. The results support the view that multiple processes (both visual/cultural learning and motor-based direct matching processes) facilitate goal prediction during observation of other peoples' actions early in infancy. PMID- 27189403 TI - Children's Play and Culture Learning in an Egalitarian Foraging Society. AB - Few systematic studies of play in foragers exist despite their significance for understanding the breadth of contexts for human development and the ontogeny of cultural learning. Forager societies lack complex social hierarchies, avenues for prestige or wealth accumulation, and formal educational institutions, and thereby represent a contrast to the contexts of most play research. Analysis of systematic observations of children's play among Aka forest foragers (n = 50, ages 4-16, M = 9.5) and Ngandu subsistence farmers (n = 48, ages 4-16, M = 9.1) collected in 2010 illustrates that while play and work trade off during development in both groups, and consistent patterns in sex-role development are evident, Aka children engage in significantly less rough-and-tumble play and competitive games than children among their socially stratified farming neighbors. PMID- 27189402 TI - Development of Teleological Explanations in Peruvian Quechua-Speaking and U.S. English-Speaking Preschoolers and Adults. AB - Teleological reasoning involves the assumption that entities exist for a purpose (giraffes have long necks for reaching leaves). This study examines how teleological reasoning relates to cultural context, by studying teleological reasoning in 61 Quechua-speaking Peruvian preschoolers (Mage = 5.3 years) and adults in an indigenous community, compared to 72 English-speaking U.S. preschoolers (Mage = 4.9 years) and university students. Data were responses to open-ended "why" questions ("Why is that mountain tall?"). Teleological explanations about nonliving natural kinds were more frequent for children than adults, and for Quechua than U.S. PARTICIPANTS: However, changes with age were importantly distinct from differences corresponding to cultural variation. Developmental and cultural differences in teleological explanations may reflect causal analysis of the features under consideration. PMID- 27189404 TI - Mapping the Cultural Learnability Landscape of Danger. AB - Cultural transmission is often viewed as a domain-general process. However, a growing literature suggests that learnability is influenced by content and context. The idea of a learnability landscape is introduced as a way of representing the effects of interacting factors on how easily information is acquired. Extending prior work (Barrett & Broesch, ), learnability of danger and other properties is compared for animals, artifacts, and foods in the urban American children (ages 4-5) and in the Shuar children in Ecuador (ages 4-9). There is an advantage for acquiring danger information that is strongest for animals and weakest for artifacts in both populations, with culture-specific variations. The potential of learnability landscapes for assessing biological and cultural influences on cultural transmission is discussed. PMID- 27189405 TI - Unselective Overimitators: The Evolutionary Implications of Children's Indiscriminate Copying of Successful and Prestigious Models. AB - Children are both shrewd about whom to copy-they selectively learn from certain adults-and overimitators-they copy adults' obviously superfluous actions. Is overimitation also selective? Does selectivity change with age? In two experiments, 161 two- to seven-year-old children saw videos of one adult receiving better payoffs or more bystander attention than another. Children then watched the adults perform unnecessary actions on novel transparent devices. Children preferred the adult who received greater payoffs or bystander attention when asked questions like "Who do you think is smarter?" but overimitated both adults' unnecessary actions equally. Although older children overimitated more, unselectivity was consistent across ages. This pattern hints at a plausible adaptive function of overimitation: acquiring rarely demonstrated behaviors by practising them immediately. PMID- 27189406 TI - Imitation, Collaboration, and Their Interaction Among Western and Indigenous Australian Preschool Children. AB - This study explored how overimitation and collaboration interact in 3- to 6-year old children in Westernized (N = 48 in Experiment 1; N = 26 in Experiment 2) and Indigenous Australian communities (N = 26 in Experiment 2). Whether working in pairs or on their own rates of overimitation did not differ. However, when the causal functions of modeled actions were unclear, the Indigenous Australian children collaborated at enhanced rates compared to the Western children. When the causal role of witnessed actions was identifiable, collaboration rates were correlated with production of causally unnecessary actions, but in the Indigenous Australian children only. This study highlights how children employ imitation and collaboration when acquiring new skills and how the latter can be influenced by task structure and cultural background. PMID- 27189407 TI - Children's Pragmatic Inferences as a Route for Learning About the World. AB - This study investigated whether children can infer category properties based on how a speaker describes an individual (e.g., saying something is a "small zib" implies that zibs are generally bigger than this one). Three- to 5-year-olds (N = 264) from a university preschool and a children's museum were tested on their ability to make this sort of contrast inference. Children made some inferences from adjective choice alone (Experiment 1); performance increased as more cues to contrast were added (Experiments 2 and 3). Control studies show that these findings are not due to the particular properties used or the structure of these tasks (Experiments 4 and 5). These findings suggest that sensitivity to speakers' production choices may help children learn about the world. PMID- 27189409 TI - Erratum. PMID- 27189408 TI - Children's Faithfulness in Imitating Language Use Varies Cross-Culturally, Contingent on Prior Experience. AB - Despite its recognized importance for cultural transmission, little is known about the role imitation plays in language learning. Three experiments examine how rates of imitation vary as a function of qualitative differences in the way language is used in a small indigenous community in Oaxaca, Mexico and three Western comparison groups. Data from one hundred thirty-eight 3- to 10-year-olds suggests that children selectively imitate when they understand the function of a given linguistic element because their culture makes frequent use of that function. When function is opaque, however, children imitate faithfully. This has implications for how children manage the imitation-innovation trade-off, and offers insight into why children imitate in language learning across development. PMID- 27189412 TI - Facile synthesis of a mechanically robust and highly porous NiO film with excellent electrocatalytic activity towards methanol oxidation. AB - Considerable research is being conducted in searching for effective anode catalysts in alkaline direct methanol fuel cells (DMFCs). Although significant progress has been achieved, it is still challenging to prepare non-Pt catalysts with both excellent activity and good durability. Herein, a highly porous NiO film is developed by a facile and fast anodization approach. The anodic NiO film demonstrates a high surface area, large mesopore volume and small crystallite size, leading to facilitated adsorption of reaction species, easy electrolyte penetration and fast reaction kinetics. Furthermore, as anodic NiO is grown in situ on a metallic substrate with strong adhesion strength and good electrical contact, it can be used directly as an anode catalyst for methanol oxidation without the need to add any binder or conducting agent. Such an additive-free approach greatly expedites the catalyst preparation process. The anodic NiO shows lower methanol oxidation potential, higher oxidation current and better catalytic durability than most of the state-of-the-art Ni-based catalysts reported elsewhere. As anodization is a simple, low cost and easily scaled up method, the work described here provides an exciting direction to speed up the practical application of alkaline DMFCs. PMID- 27189410 TI - Experimental priming of encephalitogenic Th1/Th17 cells requires pertussis toxin driven IL-1beta production by myeloid cells. AB - CD4(+) Th17 are heterogeneous in terms of cytokine production and capacity to initiate autoimmune diseases, such as experimental autoimmune encephalomyelitis (EAE). Here we demonstrate that experimental priming of encephalitogenic Th cells expressing RORgammat and T-bet and producing IL-17A, IFN-gamma and GM-CSF but not IL-10 (Th1/Th17), is dependent on the presence of pertussis toxin (PTX) at the time of immunization. PTX induces early production of IL-1beta by CD11b(+)CCR2(+)Gr1(+) myeloid cells, which are rapidly recruited to antigen draining lymph nodes. PTX-induced generation of Th1/Th17 cells is impaired in IL 1beta- and ASC-deficient mice and in mice in which myeloid cells are depleted or fail to migrate to lymph nodes and requires expression of IL-1R1 and MyD88 on both T cells and non-T cells. Collectively, these data shed light on the enigmatic function of PTX in EAE induction and suggest that inflammatory monocytes and microbial infection can influence differentiation of pathogenic Th1/Th17 cells in autoimmune diseases through production of IL-1beta. PMID- 27189413 TI - Facile P-C/C-H Bond-Cleavage Reactivity of Nickel Bis(diphosphine) Complexes. AB - Unusual cleavage of P-C and C-H bonds of the P2 N2 ligand, in heteroleptic [Ni(P2 N2 )(diphosphine)](2+) complexes under mild conditions, results in the formation of an iminium formyl nickelate featuring a C,P,P-tridentate coordination mode. The structures of both the heteroleptic [Ni(P2 N2 )(diphosphine)](2+) complexes and the resulting iminium formyl nickelate have been characterized by NMR spectroscopy and single-crystal X-ray diffraction analysis. Density functional theory (DFT) calculations were employed to investigate the mechanism of the P-C/C H bond cleavage, which involves C-H bond cleavage, hydride rotation, Ni-C/P-H bond formation, and P-C bond cleavage. PMID- 27189411 TI - A Biphasic Calcium Sulphate/Hydroxyapatite Carrier Containing Bone Morphogenic Protein-2 and Zoledronic Acid Generates Bone. AB - In orthopedic surgery, large amount of diseased or injured bone routinely needs to be replaced. Autografts are mainly used but their availability is limited. Commercially available bone substitutes allow bone ingrowth but lack the capacity to induce bone formation. Thus, off-the-shelf osteoinductive bone substitutes that can replace bone grafts are required. We tested the carrier properties of a biphasic, calcium sulphate and hydroxyapatite ceramic material, containing a combination of recombinant human bone morphogenic protein-2 (rhBMP-2) to induce bone, and zoledronic acid (ZA) to delay early resorption. In-vitro, the biphasic material released 90% of rhBMP-2 and 10% of ZA in the first week. No major changes were found in the surface structure using scanning electron microscopy (SEM) or in the mechanical properties after adding rhBMP-2 or ZA. In-vivo bone formation was studied in an abdominal muscle pouch model in rats (n = 6/group). The mineralized volume was significantly higher when the biphasic material was combined with both rhBMP-2 and ZA (21.4 +/- 5.5 mm(3)) as compared to rhBMP-2 alone (10.9 +/- 2.1 mm(3)) when analyzed using micro computed tomography (MU-CT) (p < 0.01). In the clinical setting, the biphasic material combined with both rhBMP-2 and ZA can potentially regenerate large volumes of bone. PMID- 27189414 TI - What do General Practitioners think of written reflection? A focus group study. AB - BACKGROUND: Written reflection has become a key part of evidence for assessment for General Practitioners (GPs) and GP Specialist Trainees (GPSTs), as it is thought to enhance the reflective process and demonstrate on-going learning. However, the educational value of mandatory reflection has been questioned, and there is little evidence on the acceptability of written reflection to clinicians. AIM: To explore the views of GPs and GPSTs on the use of written reflection in the MRCGP and NHS appraisal. DESIGN AND SETTING: A qualitative approach with GPs and GPSTs from the South of England. METHOD: Three focus group discussions with 11 GPs and 14 GPSTs. Thematic analysis was used on the coded texts. RESULTS: There were diverse views on the value of written reflection. Some participants with particular learning styles found it useful; some viewed it as a 'tick-box' exercise and as a game. Some questioned its value as a tool for quality improvement. Its use may have opportunity costs on clinical work, other learning and leisure time. CONCLUSION: Written reflection produced strong feelings among participants. Research is needed to gauge how commonly these feelings are held, to allow informed decisions on the place of written reflection in education and assessment. PMID- 27189415 TI - Purification and characterization of a high salt-tolerant alginate lyase from Cobetia sp. WG-007. AB - An alginate lyase producing bacterial strain, Cobetia sp. WG-007, was isolated and identified from rotting seaweed. The alginate lyase, Aly-W02, was purified by procedures of ultrafiltration, Q-Sepharose Fast Flow, Phenyl Sepharose 6 Fast Flow, and Superdex-G100 with specific activity of 21,285.5 U/mg. Aly-W02 had an apparent molecular mass of 35 kDa. It exhibited maximum activity at 45 degrees C in 50 mM sodium phosphate buffer (pH 8.5). This alginate lyase was stable in the pH range of 6.0-8.5. Among the tested metal ions, the addition of K+ , Na+ , and Mg2+ ions can enhance the enzyme activities, while Ba2+ , Ni+ , Cu2+ , Mn2+ , Zn2+ , Ag+ , and ethylenediaminetetraacetic acid decreased the activities. It displayed high salt-tolerant ability; 0.8 M NaCl or 1.5 M KCl significantly enhanced the enzyme activity. Furthermore, Aly-W02 mainly released disaccharide, trisaccharide, and tetrasaccharid from alginate. It showed potential in producing low molecular weight alginate oligosaccharides. PMID- 27189417 TI - Ferromagnetism controlled by electric field in tilted phosphorene nanoribbon. AB - Study on phosphorene nanoribbon was mostly focused on zigzag and armchair structures and no ferromagnetic ground state was observed in these systems. Here, we investigated the magnetic property of tilted black phosphorene nanoribbons (TPNRs) affected by an external electric field. We also studied the edge passivation effect on the magnetism and thermal stability of the nanoribbons. The pure TPNR displayed an edge magnetic state, but it disappeared in the edge reconstructed TPNR due to the self-passivation. In addition, we found that the bare TPNR was mechanically unstable because an imaginary vibration mode was obtained. However, the imaginary vibration mode disappeared in the edge passivated TPNRs. No edge magnetism was observed in hydrogen and fluorine passivated TPRNs. In contrast, the oxygen passivated TPNR was more stable than the pure TPNR and the edge-to-edge antiferromagntic (AFM) ground state was obtained. We found that the magnetic ground state could be tuned by the electric field from antiferromagnetic (AFM) to ferromagnetic (FM) ground state. Interestingly, the oxygen passivated TPNR displayed a half-metallic state at a proper electric field in both FM and AFM states. This finding may provoke an intriguing issue for potential spintronics application using the phosphorene nanoribbons. PMID- 27189418 TI - Need, want and demand: What is really happening with low-acuity presentations? PMID- 27189419 TI - Infused polymers for cell sheet release. AB - Tissue engineering using whole, intact cell sheets has shown promise in many cell based therapies. However, current systems for the growth and release of these sheets can be expensive to purchase or difficult to fabricate, hindering their widespread use. Here, we describe a new approach to cell sheet release surfaces based on silicone oil-infused polydimethylsiloxane. By coating the surfaces with a layer of fibronectin (FN), we were able to grow mesenchymal stem cells to densities comparable to those of tissue culture polystyrene controls (TCPS). Simple introduction of oil underneath an edge of the sheet caused it to separate from the substrate. Characterization of sheets post-transfer showed that they retain their FN layer and morphology, remain highly viable, and are able to grow and proliferate normally after transfer. We expect that this method of cell sheet growth and detachment may be useful for low-cost, flexible, and customizable production of cellular layers for tissue engineering. PMID- 27189416 TI - Colorectal cancer. AB - Colorectal cancer had a low incidence several decades ago. However, it has become a predominant cancer and now accounts for approximately 10% of cancer-related mortality in western countries. The 'rise' of colorectal cancer in developed countries can be attributed to the increasingly ageing population, unfavourable modern dietary habits and an increase in risk factors, such as smoking, low physical exercise and obesity. New treatments for primary and metastatic colorectal cancer have emerged, providing additional options for patients; these treatments include laparoscopic surgery for primary disease, more-aggressive resection of metastatic disease (such as liver and pulmonary metastases), radiotherapy for rectal cancer, and neoadjuvant and palliative chemotherapies. However, these new treatment options have had limited impact on cure rates and long-term survival. For these reasons, and the recognition that colorectal cancer is long preceded by a polypoid precursor, screening programmes have gained momentum. This Primer provides an overview of the current state of the art of knowledge on the epidemiology and mechanisms of colorectal cancer, as well as on diagnosis and treatment. PMID- 27189420 TI - Morphological and molecular descriptions of Moniliformis saudi sp. n. (Acanthocephala: Moniliformidae) from the desert hedgehog, Paraechinus aethiopicus (Ehrenberg) in Saudi Arabia, with a key to species and notes on histopathology. AB - A new acanthocepohalan species, Moniliformis saudi sp. n. is described from the desert hedgehog, Paraechinus aethiopicus (Ehrenberg), in central Saudi Arabia. Fourteen other valid species of Moniliformis Travassos, 1915 are recognised. The new species of Moniliformis is distinguished by having a small proboscis (315-520 um long and 130-208 um wide) with two apical pores, 14 rows of 8 hooks each and small hooks, thre largest being 25-31 um long anteriorly. Distinguishing features are incorporated in a dichotomous key to the species of Moniliformis. The description is augmented by scanning electron microscopical (SEM) observation and DNA analysis of nuclear (18S rRNA) and mitochondrial (cytochrome oxidase subunit 1; cox1) gene sequences. Attached worms cause extensive damage to the immediate area of attachment in the host intestine. This includes tissue necrosis and blood loss due to damage to capillary beds. Worms also obstruct essential absorbing surfaces. PMID- 27189423 TI - Adjuvant indoleamine 2,3-dioxygenase enzyme inhibition for comprehensive management of epilepsy and comorbid depression. AB - Epilepsy is one of the major neurological disorders frequently associated with psychiatric disorders such as depression. Alteration of tryptophan metabolism towards kynurenine pathway may be one of the plausible reasons for association of depression in epilepsy. Hence, this study was envisaged to evaluate the dose dependent inhibition of indoleamine 2,3-dioxygenase (IDO) enzyme (responsible for shifting tryptophan metabolism) employing minocycline with valproic acid for comprehensive management of epilepsy and comorbid depression. Kindling was induced in male swiss albino mice by administration of pentylenetetrazole subconvulsive dose (35mg/kg, i.p.) at an interval of 48+/-2h. Kindled animals were treated with saline, valproate (300mg/kg/day i.p.), valproate in combination with different doses of minocycline (10mg/kg; 20mg/kg; 40mg/kg)/day i.p. and minocycline per se (40mg/kg/day i.p.) for 15 days. Except naive, all the groups were challenged with pentylenetetrazole (35mg/kg i.p.) on day 5, 10, and 15 to evaluate the seizure severity score. Depression was evaluated in all experimental groups using tail suspension and forced swim test on days 1, 5, 10 and 15, 2h after pentylenetetrazole challenge. Results suggested that saline treated kindled animals were significantly associated with depression. Chronic valproate treatment significantly reduced seizure severity score but unable to ameliorate the associated depression. Minocycline supplementation with valproic acid dose dependently ameliorated depression associated with epilepsy. Neurochemical and biochemical findings also supported the behavioural findings of the study. Thus, our results suggested that supplementation of IDO enzyme inhibitors with valproic acid could be explored further for comprehensive management of epilepsy and associated depression. PMID- 27189422 TI - The Mobile Solutions for Immunization (M-SIMU) Trial: A Protocol for a Cluster Randomized Controlled Trial That Assesses the Impact of Mobile Phone Delivered Reminders and Travel Subsidies to Improve Childhood Immunization Coverage Rates and Timeliness in Western Kenya. AB - BACKGROUND: Text message (short message service, SMS) reminders and incentives are two demand-side interventions that have been shown to improve health care seeking behaviors by targeting participant characteristics such as forgetfulness, lack of knowledge, and transport costs. Applying these interventions to routine pediatric immunizations may improve vaccination coverage and timeliness. OBJECTIVE: The Mobile Solutions for Immunization (M-SIMU) trial aims to determine if text message reminders, either with or without mobile phone-based incentives, sent to infant's parents can improve immunization coverage and timeliness of routine pediatric vaccines in rural western Kenya. METHODS: This is a four-arm, cluster, randomized controlled trial. Villages are randomized to one of four study arms prior to enrollment of participants. The study arms are: (1) no intervention (a general health-related text message will be texted to this group at the time of enrollment), (2) text message reminders only, (3) text message reminders and a 75 Kenyan Shilling (KES) incentive, or (4) text message reminders and a KES200 incentive. Participants assigned to study arms 2-4 will receive two text message reminders; sent 3 days before and one day before the scheduled immunization visit at 6, 10, and 14 weeks for polio and pentavalent (containing diphtheria, tetanus, pertussis, hepatitis B, and Haemophilus influenza type b antigens) type b antigens) vaccines, and at 9 months for measles vaccine. Participants in incentive arms will, in addition to text message reminders as above, receive mobile phone-based incentives after each timely vaccination, where timely is defined as vaccination within 2 weeks of the scheduled date for each of the four routine expanded program immunization (EPI) vaccination visits. Mother infant pairs will be followed to 12 months of age where the primary outcome, a fully immunized child, will be ascertained. A fully immunized child is defined as a child receiving vaccines for bacille Calmette-Guerin, three doses of pentavalent and polio, and measles by 12 months of age. General estimating equation (GEE) models that account for clustering will be employed for primary outcome analyses. RESULTS: Enrollment was completed in October 2014. Twelve month follow-up visits to ascertain immunization status from the maternal and child health booklet were completed in February 2016. CONCLUSIONS: This is one of the first studies to examine the effect of text message reminders on immunization coverage and timeliness in a lower income country and is the first study to assess the effect of mobile money-based incentives to improve immunization coverage. TRIAL REGISTRATION: Clinicaltrials.gov NCT01878435; https://clinicaltrials.gov/ct2/show/NCT01878435 (Archived by WebCite at http://www.webcitation.org/6hQlwGYJR). PMID- 27189425 TI - Evolution of CCL11: genetic characterization in lagomorphs and evidence of positive and purifying selection in mammals. AB - The interactions between chemokines and their receptors are crucial for differentiation and activation of inflammatory cells. CC chemokine ligand 11 (CCL11) binds to CCR3 and to CCR5 that in leporids underwent gene conversion with CCR2. Here, we genetically characterized CCL11 in lagomorphs (leporids and pikas). All lagomorphs have a potentially functional CCL11, and the Pygmy rabbit has a mutation in the stop codon that leads to a longer protein. Other mammals also have mutations at the stop codon that result in proteins with different lengths. By employing maximum likelihood methods, we observed that, in mammals, CCL11 exhibits both signatures of purifying and positive selection. Signatures of purifying selection were detected in sites important for receptor binding and activation. Of the three sites detected as under positive selection, two were located close to the stop codon. Our results suggest that CCL11 is functional in all lagomorphs, and that the signatures of purifying and positive selection in mammalian CCL11 probably reflect the protein's biological roles. PMID- 27189424 TI - LPS stimulates IgM production in vivo without help from non-B cells. AB - Gram-negative bacterial LPS induce murine B-cell activation and innate (polyclonal) Ab production. Mouse B cells express the LPS signaling receptor (TLR4), yet how LPS activates B-cell responses in vivo is not known. Can LPS directly stimulate B cells to induce innate Ab production? Is activation of non-B cells also required? To address these questions, we transfused LPS-responsive (Tlr4(+/+)) or non-responsive (Tlr4(-/-)) B cells into LPS-responsive or non responsive mice. Increased expression of the early activation markers CD69 and CD86 could be induced on transfused Tlr4(-/-) B cells by injecting LPS subcutaneously into Tlr4(+/+) mice, demonstrating indirect activation of B cells by TLR4-responsive non-B cells in vivo, but the Tlr4(-) (/) (-) B cells did not increase serum IgM levels. In contrast, when Tlr4(-/-) recipients were transfused with Tlr4(+/+) B cells, LPS induced large amounts of serum IgM and LPS could also enhance specific Ab production to a protein that was co-injected with it (adjuvant response). Thus, LPS-exposed non-B cells mediated increased surface expression of early B-cell activation markers, but this response did not predict innate Ab responses or LPS adjuvanticity in vivo Direct stimulation of B cells by LPS via TLR4 was necessary and sufficient to induce B cells to produce Ab in vivo. PMID- 27189426 TI - Chemometric analysis of attenuated total reflectance infrared spectra of Proteus mirabilis strains with defined structures of LPS. AB - Proteus spp. strains are some of the most important pathogens associated with complicated urinary tract infections and bacteremia affecting patients with immunodeficiency and long-term urinary catheterization. For epidemiological purposes, various molecular typing methods have been developed for this pathogen. However, these methods are labor intensive and time consuming. We evaluated a new method of differentiation between strains. A collection of Proteus spp. strains was analyzed by attenuated total reflectance Fourier transform infrared (ATR FT IR) spectroscopy in the mid-infrared region. ATR FT-IR spectroscopy used in conjunction with a diamond ATR accessory directly produced the biochemical profile of the surface chemistry of bacteria. We conclude that a combination of ATR FT-IR spectroscopy and mathematical modeling provides a fast and reliable alternative for discrimination between Proteus isolates, contributing to epidemiological research. PMID- 27189421 TI - Retinoblastoma. AB - Retinoblastoma is a rare cancer of the infant retina that is diagnosed in approximately 8,000 children each year worldwide. It forms when both retinoblastoma gene (RB1) alleles are mutated in a susceptible retinal cell, probably a cone photoreceptor precursor. Loss of the tumour-suppressive functions of the retinoblastoma protein (pRB) leads to uncontrolled cell division and recurrent genomic changes during tumour progression. Although pRB is expressed in almost all tissues, cone precursors have biochemical and molecular features that may sensitize them to RB1 loss and enable tumorigenesis. Patient survival is >95% in high-income countries but <30% globally. However, outcomes are improving owing to increased disease awareness for earlier diagnosis, application of new guidelines and sharing of expertise. Intra-arterial and intravitreal chemotherapy have emerged as promising methods to salvage eyes that with conventional treatment might have been lost. Ongoing international collaborations will replace the multiple different classifications of eye involvement with standardized definitions to consistently assess the eligibility, efficacy and safety of treatment options. Life-long follow-up is warranted, as survivors of heritable retinoblastoma are at risk for developing second cancers. Defining the molecular consequences of RB1 loss in diverse tissues may open new avenues for treatment and prevention of retinoblastoma, as well as second cancers, in patients with germline RB1 mutations. PMID- 27189427 TI - Dectin-1 and Dectin-2 promote control of the fungal pathogen Trichophyton rubrum independently of IL-17 and adaptive immunity in experimental deep dermatophytosis. AB - Dermatophytoses are chronic fungal infections, the main causative agent of which is Trichophyton rubrum (T. rubrum). Despite their high occurrence worldwide, the immunological mechanisms underlying these diseases remain largely unknown. Here, we uncovered the C-type lectin receptors, Dectin-1 and Dectin-2, as key elements in the immune response to T. rubrum infection in a model of deep dermatophytosis. In vitro, we observed that deficiency in Dectin-1 and Dectin-2 severely compromised cytokine production by dendritic cells. In vivo, mice lacking Dectin 1 and/or Dectin-2 showed an inadequate pro-inflammatory cytokine production in response to T. rubrum infection, impairing its resolution. Strikingly, neither adaptive immunity nor IL-17 response were required for fungal clearance, highlighting innate immunity as the main checkpoint in the pathogenesis of T. rubrum infection. PMID- 27189429 TI - Overview provides insights on the current status and future of meta-epidemiology. PMID- 27189428 TI - Anemonin improves intestinal barrier restoration and influences TGF-beta1 and EGFR signaling pathways in LPS-challenged piglets. AB - The present study was aimed at investigating whether dietary anemonin could alleviate LPS-induced intestinal injury and improve intestinal barrier restoration in a piglet model. Eighteen 35-d-old pigs were randomly assigned to three treatment groups (control, LPS and LPS+anemonin). The control and LPS groups were fed a basal diet, and the LPS + anemonin group received the basal diet + 100 mg anemonin/kg diet. After 21 d of feeding, the LPS- and anemonin treated piglets received i.p. administration of LPS; the control group received saline. At 4 h post-injection, jejunum samples were collected. The results showed that supplemental anemonin increased villus height and transepithelial electrical resistance, and decreased crypt depth and paracellular flux of dextran (4 kDa) compared with the LPS group. Moreover, anemonin increased tight junction claudin 1, occludin and ZO-1 expression in the jejunal mucosa, compared with LPS group. Anemonin also decreased TNF-alpha, IL-6, IL-8 and IL-1beta mRNA expression. Supplementation with anemonin also increased TGF-beta1 mRNA and protein expression, Smad4 and Smad7 mRNA expressions, and epidermal growth factor and epidermal growth factor receptor (EGFR) mRNA expression in the jejunal mucosa. These findings suggest that dietary anemonin attenuates LPS-induced intestinal injury by improving mucosa restoration, alleviating intestinal inflammation and influencing TGF-beta1 canonical Smads and EGFR signaling pathways. PMID- 27189430 TI - The Soil Geochemistry in the Beardmore Glacier Region, Antarctica: Implications for Terrestrial Ecosystem History. AB - Although most models suggest continental Antarctica was covered by ice during the Last Glacial Maximum (LGM) it has been speculated that endemic species of soil invertebrates could have survived the Pleistocene at high elevation habitats protruding above the ice sheets. We analyzed a series of soil samples from different elevations at three locations along the Beardmore Glacier in the Transantarctic Mountains (in order of increasing elevation): Ebony Ridge (ER), Cloudmaker (CM), and Meyer Desert (MD). Geochemical analyses show the MD soils, which were exposed during the LGM, were the least weathered compared to lower elevations, and also had the highest total dissolved solids (TDS). MD soils are dominated by nitrate salts (NO3/Cl ratios >10) that can be observed in SEM images. High delta(17)O and delta(18)O values of the nitrate indicate that its source is solely of atmospheric origin. It is suggested that nitrate concentrations in the soil may be utilized to determine a relative "wetting age" to better assess invertebrate habitat suitability. The highest elevation sites at MD have been exposed and accumulating salts for the longest times, and because of the salt accumulations, they were not suitable as invertebrate refugia during the LGM. PMID- 27189431 TI - Correlating structure and electronic band-edge properties in organolead halide perovskites nanoparticles. AB - After having emerged as primary contenders in the race for highly efficient optoelectronics materials, organolead halide perovskites (OHLP) are now being investigated in the nanoscale regime as promising building blocks with unique properties. For example, unlike their bulk counterpart, quantum dots of OHLP are brightly luminescent, owing to large exciton binding energies that cannot be rationalized solely on the basis of quantum confinement. Here, we establish the direct correlation between the structure and the electronic band-edge properties of CH3NH3PbBr3 nanoparticles. Complementary structural and spectroscopic measurements probing long-range and local order reveal that lattice strain influences the nature of the valence band and modifies the subtle stereochemical activity of the Pb(2+) lone-pair. More generally, this work demonstrates that the stereochemical activity of the lone-pair at the metal site is a specific physicochemical parameter coupled to composition, size and strain, which can be employed to engineer novel functionalities in OHLP nanomaterials. PMID- 27189432 TI - High-performance liquid chromatography - Ultraviolet method for the determination of total specific migration of nine ultraviolet absorbers in food simulants based on 1,1,3,3-Tetramethylguanidine and organic phase anion exchange solid phase extraction to remove glyceride. AB - The glyceride in oil food simulant usually causes serious interferences to target analytes and leads to failure of the normal function of the RP-HPLC column. In this work, a convenient HPLC-UV method for the determination of the total specific migration of nine ultraviolet (UV) absorbers in food simulants was developed based on 1,1,3,3-tetramethylguanidine (TMG) and organic phase anion exchange (OPAE) SPE to efficiently remove glyceride in olive oil simulant. In contrast to the normal ion exchange carried out in an aqueous solution or aqueous phase environment, the OPAE SPE was performed in the organic phase environments, and the time-consuming and challenging extraction of the nine UV absorbers from vegetable oil with aqueous solution could be readily omitted. The method was proved to have good linearity (r>=0.99992), precision (intra-day RSD<=3.3%), and accuracy(91.0%<=recoveries<=107%); furthermore, the lower limit of quantifications (0.05-0.2mg/kg) in five types of food simulants(10% ethanol, 3% acetic acid, 20% ethanol, 50% ethanol and olive oil) was observed. The method was found to be well suited for quantitative determination of the total specific migration of the nine UV absorbers both in aqueous and vegetable oil simulant according to Commission Regulation (EU) No. 10/2011. Migration levels of the nine UV absorbers were determined in 31 plastic samples, and UV-24, UV-531, HHBP and UV-326 were frequently detected, especially in olive oil simulant for UV-326 in PE samples. In addition, the OPAE SPE procedure was also been applied to efficiently enrich or purify seven antioxidants in olive oil simulant. Results indicate that this procedure will have more extensive applications in the enriching or purification of the extremely weak acidic compounds with phenol hydroxyl group that are relatively stable in TMG n-hexane solution and that can be barely extracted from vegetable oil. PMID- 27189433 TI - Comparison between polymerized ionic liquids synthesized using chain-growth and step-growth mechanisms used as stationary phase in gas chromatography. AB - In this study the merits of polymerized imidazolium based ionic liquid (PIL) stationary phases obtained via condensation and free radical polymerizations are compared as stationary phases in gas chromatography (GC). Poly(1-vinyl-3-butyl imidazolium - bis(trifluoromethane)sulfonamide) (poly(ViC4Im(+) NTf2(-))) was obtained via a chain-growth mechanism while poly(propylimidazolium-NTf2) (poly(C3Im(+) NTf2(-))) was synthesized via a step-growth polymerization. The thermal stability of both polymers was assessed using thermal gravimetric analysis and compared with bleeding profiles obtained from the statically coated GC columns (30m*0.25mm*0.25MUm). The performance was compared to what could be obtained on commercially available 1,5-di(2,3-dimethylimidazolium)pentane(2+) 2NTf2(-) (SLB-IL111) ionic liquid based columns. It was observed that the step growth polymer was more thermally stable, up to 325 degrees C, while the chain growth polymer showed initial degradation at 250 degrees C. Both polymers allowed reaching minimal plate heights of 0.400-0.500mm for retained solutes such as benzaldehyde, acetophenone, 1-methylnaphthalene and aniline. Assessment of the McReynolds constants illustrated that the polarity of the step-growth polymer was similar to the SLB-IL111 column, while displaying improved column stability. The PIL phases and particularly the so far little studied condensation based polymer shows particular retention and satisfactory column performance for polar moieties such as esters, amine and carbonyl functionalities. PMID- 27189434 TI - Metal ion binding to phospholipid bilayers evaluated by microaffinity chromatography. AB - Group I and II ion binding to phospholipid membranes was evaluated by affinity chromatography utilizing a new stationary phase system based on lipid bilayers supported within large-pore particles composed of Stober silica spheres. Using an inductively coupled plasma mass spectrometer for detection, robust determination of binding selectivity within group II ions is achieved with capillary columns containing nanomole quantities of lipid and using picomoles of metal analyte. Columns with a unique lipid formulation can be prepared within three hours using a solvent-casting assembly method. The observable thermotropic phase behavior of dipalmitoylphosphatidylcholine has a significant effect on alkaline metal binding and demonstrates the dynamic nature of the supported bilayers. Of the group I ions, only lithium exhibits retention with neutral phosphatidylcholine bilayer stationary phases. A comparison of Stober-based supports with two commercially available large-pore silicas reveals the effect that particle structure has on analyte accessibility to the bilayer surface as evaluated by retention per supported lipid mass. PMID- 27189436 TI - Successful vaginal delivery at term following ventro-fixation procedure for uterine incarceration. PMID- 27189435 TI - Context-dependent switch in chemo/mechanotransduction via multilevel crosstalk among cytoskeleton-regulated MRTF and TAZ and TGFbeta-regulated Smad3. AB - Myocardin-related transcription factor (MRTF) and TAZ are major mechanosensitive transcriptional co-activators that link cytoskeleton organization to gene expression. Despite many similarities in their regulation, their physical and/or functional interactions are unknown. Here we show that MRTF and TAZ associate partly through a WW domain-dependent mechanism, and exhibit multilevel crosstalk affecting each other's expression, transport and transcriptional activity. Specifically, MRTF is essential for TAZ expression; TAZ and MRTF inhibit each other's cytosolic mobility and stimulus-induced nuclear accumulation; they antagonize each other's stimulatory effect on the alpha-smooth muscle actin (SMA) promoter, which harbours nearby cis-elements for both, but synergize on isolated TEAD-elements. Importantly, TAZ confers Smad3 sensitivity to the SMA promoter. Thus, TAZ is a context-dependent switch during mechanical versus mechano/chemical signalling, which inhibits stretch-induced but is indispensable for stretch+TGFbeta-induced SMA expression. Crosstalk between these cytoskeleton regulated factors seems critical for fine-tuning mechanical and mechanochemical transcriptional programmes underlying myofibroblast transition, wound healing and fibrogenesis. PMID- 27189437 TI - Association of fish consumption and dietary intake of marine n-3 PUFA with myocardial infarction in a prospective Danish cohort study. AB - Several studies have investigated the potential benefits of marine n-3 PUFA in CVD, generally suggesting a lower risk of CHD. However, recent trials have questioned these results. This study investigated the association of fish consumption with dietary intake of marine n-3 PUFA with incident myocardial infarction (MI). In a Danish cohort study, 57 053 subjects between 50 and 64 years of age were enrolled from 1993 to 1997. From national registries, we identified all cases of incident MI. Dietary fish consumption was assessed using a semi-quantitative food questionnaire, including twenty-six questions regarding fish intake. In addition, we calculated the intake of total and individual marine n-3 PUFA. During a median follow-up of 17.0 years, we identified 3089 cases of incident MI. For both men and women, a high intake of fatty fish was inversely related to incident MI. Thus, when comparing the highest and the lowest quintile of fatty fish intake, we found a 12 % lower relative risk of MI in men (hazard ratio (HR) 0.88; 95 % CI 0.77, 1.00) and a 22 % lower relative risk in women (HR 0.78; 95 % CI 0.63, 0.96) after adjustments. For women, similar associations were observed for individual and total marine n-3 PUFA. In contrast, intake of lean fish was not associated with MI. In conclusion, incident MI was inversely related to a high intake of fatty fish, but not lean fish. However, test for trends across quintiles was not statistically significant. In general, this study supports the view that consumption of fatty fish may protect against MI. PMID- 27189438 TI - Generation of a high resolution map of sRNAs from Fusarium graminearum and analysis of responses to viral infection. AB - Previously, we characterized F. graminearum hypovirus 1 (FgHV1) and F. graminearum hypovirus 2 (FgHV2), which are the only two hypoviruses in F. graminearum that are closely related to Cryphonectria hypovirus 1 (CHV1) and Cryphonectria hypovirus 2 (CHV2) in the Hypoviridae family. In this study, we preliminarily elucidated the RNA silencing mechanism of the F. graminearum/hypovirus system from a small RNA (sRNA) perspective by using HiSeq deep sequencing. The length distributions of F. graminearum sRNA were altered by hypoviral infection. Potential microRNA-like (milRNA) candidates were differentially expressed between the hypovirus-free and hypovirus-infected library types. Extensive virus-derived small interfering RNAs (vsiRNAs) were also principally defined. The 1,831,081 and 3,254,758 total reads generated from the FgHV1 and FgHV2 genomes in F. graminearum yielded the first high-resolution sRNA maps of fungal viruses. In addition, extensive bioinformatics searches identified a large number of transcripts that are potentially targeted by vsiRNAs, several of which were effectively down-regulated. In particular, the RNA silencing related genes FgDicer1 and FgRdRp5 were predicted targets of FgHV1- and FgHV2 derived siRNAs, possibly revealing a novel anti-RNA silencing strategy employed by mycoviruses. PMID- 27189440 TI - De novo assembly and annotation of the marine mysid (Neomysis awatschensis) transcriptome. AB - We sequenced the whole transcriptome of the marine mysid Neomysis awatschensis (Crustacea: Mysidacea) using Illumina RNA-seq. De novo assembly was performed with 14,018,702 raw reads using Trinity, resulting in 82,434 contigs. Transdecoder found 22,141 candidate coding contigs with homology to other species by BLAST analysis. Functional gene annotation was performed by Gene Ontology, InterProScan, and KEGG pathway analyses. We generated an expressed gene catalog for the mysid N. awatschensis to serve as a resource for marine environmental genomic and ecotoxicogenomic studies focused on uncovering the molecular mechanisms underlying the responses of N. awatschensis to environmental stressors and chemicals. PMID- 27189439 TI - Genomic conservation of erythropoietic microRNAs (erythromiRs) in white-blooded Antarctic icefish. AB - White-blooded Antarctic crocodile icefish are the only vertebrates known to lack functional hemoglobin genes and red blood cells throughout their lives. We do not yet know, however, whether extinction of hemoglobin genes preceded loss of red blood cells or vice versa, nor whether erythropoiesis regulators disappeared along with hemoglobin genes in this erythrocyte-null clade. Several microRNAs, which we here call erythromiRs, are expressed primarily in developing red blood cells in zebrafish, mouse, and humans. Abrogating some erythromiRs, like mir144 and mir451a, leads to profound anemia, demonstrating a functional role in erythropoiesis. Here, we tested two not mutually exclusive hypotheses: 1) that the loss of one or more erythromiR genes extinguished the erythropoietic program of icefish and/or led to the loss of globin gene expression through pseudogenization; and 2) that some erythromiR genes were secondarily lost after the loss of functional hemoglobin and red blood cells in icefish. We explored small RNA transcriptomes generated from the hematopoietic kidney marrow of four Antarctic notothenioids: two red-blooded species (bullhead notothen Notothenia coriiceps and emerald notothen Trematomus bernacchii) and two white-blooded icefish (blackfin icefish Chaenocephalus aceratus and hooknose icefish Chionodraco hamatus). The N. coriiceps genome assembly anchored analyses. Results showed that, like the two red-blooded species, the blackfin icefish genome possessed and the marrow expressed all known erythromiRs. This result indicates that loss of hemoglobin and red blood cells in icefish was not caused by loss of known erythromiR genes. Furthermore, expression of only one erythromiR, mir96, appears to have been lost after the loss of red blood cells and hemoglobin expression was not detected in the erythropoietic organ of hooknose icefish but was present in blackfin icefish. All other erythromiRs investigated, including mir144 and mir451a, were expressed by all four species and thus are present in the genomes of at least the two white-blooded icefish. Our results rule out the hypothesis that genomic loss of any known erythromiRs extinguished erythropoiesis in icefish, and suggest that after the loss of red blood cells, few erythromiRs experienced secondary loss. Results suggest that functions independent of erythropoiesis maintained erythromiRs, thereby highlighting the evolutionary resilience of miRNA genes in vertebrate genomes. PMID- 27189441 TI - Intestinal obstruction requiring fecal diversion due to rectal hematoma following a hemorrhoid laser procedure (HeLP). PMID- 27189442 TI - Critical concepts and important anatomic landmarks encountered during transanal total mesorectal excision (taTME): toward the mastery of a new operation for rectal cancer surgery. AB - Over the past 3 years, colorectal surgeons have begun to adapt the technique of transanal total mesorectal excision. As international experience has been quickly forged, an improved recognition of the pitfalls and the practical details of this disruptive technique have been realized. The purpose of this technical note was to express the various nuances of transanal total mesorectal excision as learned during the course of its clinical application and international teaching, so as to rapidly communicate and share important insights with other surgeons who are in the early adoption phase of this approach. The technical points specific to transanal total mesorectal excision are addressed herein. When correctly applied, these will likely improve the quality of surgery and decrease morbidity attributable to inexperience with the transanal approach to total mesorectal excision. PMID- 27189444 TI - One-pot multiple reactions: asymmetric synthesis of 2,6-cis-disubstituted piperidine alkaloids from chiral aziridine. AB - A divergent, new, and highly stereoselective synthesis of cis-2,6-disubstituted piperidine natural products including isosolenopsins, deoxocassine, and spectaline was achieved from chiral aziridine decorated with appropriate alkyl chains for isosolenopsins or alkynyl groups for deoxocassine and spectaline at C2. The characteristic feature of this synthesis is one-pot sequential reactions under atmospheric hydrogen including the reduction of alkyne (for deoxocassine and spectaline), reductive ring-opening of aziridine, debenzylation, and intramolecular reductive amination in high yields. The prerequisite aziridines were elaborated from commercially available (2S)-hydroxymethylaziridine through oxidation, Wittig olefination, and the Grignard reaction for isosolenopsins or substrate-controlled lithium alkynylate addition for deoxocassine and spectaline. PMID- 27189443 TI - Predictors of wound dehiscence and its impact on mortality after abdominoperineal resection: data from the National Surgical Quality Improvement Program. AB - BACKGROUND: Wound dehiscence is a known complication following abdominoperineal resection (APR) and can have a negative impact on recovery and outcome. The aim of this study was to determine the predictors of post-APR 30-day abdominal and/or perineal wound dehiscence, readmission, and reoperation, and to assess the impact of wound dehiscence on 30-day mortality. METHODS: All patients undergoing APR between 2005 and 2012 were analyzed using the American College of Surgeons National Surgical Quality Improvement Program. RESULTS: There were 5161 patients [male = 3076 (59.6 %)] with a mean age of 61.9 +/- 14.3 years. Mean body mass index was 27.4 +/- 6.6 kg/m(2). The most common indication for surgery was rectal cancer (79.1 %), followed by inflammatory bowel disease (8.2 %). The overall rate of wound dehiscence was 2.7 % (n = 141). Older age (p = 0.013), baseline dyspnea (p = 0.043), smoking history (p = 0.009), and muscle flap creation (p <= 0.001) were independently associated with the risk of dehiscence. No association was observed between omental flap creation and dehiscence risk (p = 0.47). The 30-day readmission rate (15.6 vs. 5.6 %, p <= 0.001) and need for reoperation (39 vs. 6.6 %, p <= 0.001) were significantly higher in patients who experienced dehiscence. Dehiscence was an independent risk factor for 30-day mortality [OR = 2.69 (1.02-7.08), p = 0.045)]. CONCLUSIONS: Older age, baseline dyspnea, smoking, and the use of muscle flap were associated with higher risk of wound dehiscence following APR. Patients with wound dehiscence had a higher rate of readmission and need for reoperation, and an increased risk of 30-day mortality. PMID- 27189445 TI - Response to Letter to the Editor re: Cananzi, et al.: Surgery of leiomyosarcoma of the inferior vena cava. PMID- 27189446 TI - To spray or not to spray? Understanding participation in an indoor residual spray campaign in Arequipa, Peru. AB - Current low participation rates in vector control programmes in Arequipa, Peru complicate the control of Chagas disease. Using focus groups (n = 17 participants) and semi-structured interviews (n = 71) conducted in March and May 2013, respectively, we examined barriers to and motivators of household participation in an indoor residual spray (IRS) campaign that had taken place one year prior in Arequipa. The most common reported barriers to participation were inconvenient spray times due to work obligations, not considering the campaign to be necessary, concerns about secondary health impacts (e.g. allergic reactions to insecticides), and difficulties preparing the home for spraying (e.g. moving heavy furniture). There was also a low perception of risk for contracting Chagas disease that might affect participation. The main motivator to participate was to ensure personal health and well-being. Future IRS campaigns should incorporate more flexible hours, including weekends; provide appropriate educational messages to counter concerns about secondary health effects; incorporate peer educators to increase perceived risk to Chagas in community; obtain support from community members and leaders to build community trust and support for the campaign; and assist individuals in preparing their homes. Enhancing community trust in both the need for the campaign and its operations is key. PMID- 27189447 TI - Integrated environmental characterization of the contaminated marine coastal area of Taranto, Ionian Sea (southern Italy). PMID- 27189448 TI - A critical review of the development, current hotspots, and future directions of Lake Taihu research from the bibliometrics perspective. AB - Lake Taihu, as the important drinking water source of the Yangtze River Delta urban agglomeration and the third largest freshwater lake in China, has experienced serious lake eutrophication and water quality deterioration in the past three decades. Growing scientific, political, and public attention has been given to the water quality of Lake Taihu. This study aimed to conduct a comparative quantitative and qualitative analysis of the development, current hotspots, and future directions of Lake Taihu research using a bibliometric analysis of eight well-studied lakes (Lake Taihu, Lake Baikal, Lake Biwa, Lake Erie, Lake Michigan, Lake Ontario, Lake Superior and Lake Victoria) around the world based on the Science Citation Index (SCI) database. A total of 1582 papers discussing Lake Taihu research were published in 322 journals in the past three decades. However, the first paper about Lake Taihu research was not found in the SCI database until 1989, and there were only zero, one, or two papers each year from 1989 to 1995. There had been rapid development in Lake Taihu research since 1996 and a sharp increase in papers since 2005. A keyword analysis showed that "sediment," "eutrophication", "Microcystis aeruginosa", "cyanobacterial blooms", and "remote sensing" were the most frequently used keywords of the study subject. Owing to its significant impact on aquatic ecosystems, a crucial emphasis has been placed on climate change recently. In addition, the future focuses of research directions, including (1) environmental effects of physical processes; (2) nutrient cycles and control and ecosystem responses; (3) cyanobacteria bloom monitoring, causes, forecast and management; (4) eutrophication and climate change interactions; and (5) ecosystem degradation mechanism and ecological practice of lake restoration, are presented based on the keyword analysis. Through multidisciplinary fields (physics, chemistry, and biology) cross and synthesis study of Lake Taihu, the development of shallow lake limnology will be largely promoted. PMID- 27189449 TI - Exploring new DGT samplers containing a polymer inclusion membrane for mercury monitoring. AB - A polymer inclusion membrane (PIM) made of cellulose triacetate as a polymer and the task specific ionic liquid (IL) trioctylmethylammonium thiosalicylate (TOMATS) was assembled as a new Diffusive Gradients in Thin film (DGT) device to test its efficiency as a binding phase for mercury (Hg) monitoring. The effect of IL content was assessed, showing that higher TOMATS percentage is better for short deployment studies (up to hours), whereas for long-term exposure (up to days), a lower content can be more suitable. Different configurations of PIM-DGT samplers have been tested under controlled conditions and compared with in-house DGT conventional ones, manufactured with thiol groups as resin layer, for the determination of labile Hg. According to our results, a nonlinear accumulation profile of Hg with deployment time for the different designs of PIM-DGT was observed, limiting the range of applicability of the DGT technique. Promising results for the efficient removal of Hg from aqueous solutions and/or environmental monitoring studies were obtained with TOMATS. PMID- 27189450 TI - Economics of carbon dioxide capture and utilization-a supply and demand perspective. AB - Lately, the technical research on carbon dioxide capture and utilization (CCU) has achieved important breakthroughs. While single CO2-based innovations are entering the markets, the possible economic effects of a large-scale CO2 utilization still remain unclear to policy makers and the public. Hence, this paper reviews the literature on CCU and provides insights on the motivations and potential of making use of recovered CO2 emissions as a commodity in the industrial production of materials and fuels. By analyzing data on current global CO2 supply from industrial sources, best practice benchmark capture costs and the demand potential of CO2 utilization and storage scenarios with comparative statics, conclusions can be drawn on the role of different CO2 sources. For near term scenarios the demand for the commodity CO2 can be covered from industrial processes, that emit CO2 at a high purity and low benchmark capture cost of approximately 33 ?/t. In the long-term, with synthetic fuel production and large scale CO2 utilization, CO2 is likely to be available from a variety of processes at benchmark costs of approx. 65 ?/t. Even if fossil-fired power generation is phased out, the CO2 emissions of current industrial processes would suffice for ambitious CCU demand scenarios. At current economic conditions, the business case for CO2 utilization is technology specific and depends on whether efficiency gains or substitution of volatile priced raw materials can be achieved. Overall, it is argued that CCU should be advanced complementary to mitigation technologies and can unfold its potential in creating local circular economy solutions. PMID- 27189451 TI - Bioelectricity generation and dewatered sludge degradation in microbial capacitive desalination cell. AB - Microbial desalination cell (MDC) is a new approach for the synergy in bioelectricity generation, desalination and organic waste treatment without additional power input. However, current MDC systems cause salt accumulation in anodic wastewater and sludge. A microbial capacitive desalination cell (MCDC) with dewatered sludge as anodic substrate was developed to address the salt migration problem and improve the sludge recycling value by special designed membrane assemblies, which consisted of cation exchange membranes (CEMs), layers of activated carbon cloth (ACC), and nickel foam. Experimental results indicated that the maximum power output of 2.06 W/m3 with open circuit voltage (OCV) of 0.942 V was produced in 42 days. When initial NaCl concentration was 2 g/L, the desalinization rate was about 15.5 mg/(L.h) in the first 24 h, indicating that the MCDC reactor was suitable to desalinize the low concentration salt solution rapidly. The conductivity of the anodic substrate decreased during the 42-day operation; the CEM/ACC/Ni assemblies could effectively restrict the salt accumulation in MCDC anode and promote dewatered sludge effective use by optimizing the dewatered sludge properties, such as organic matter, C/N, pH value, and electric conductivity (EC). PMID- 27189453 TI - Biofilter for generation of concentrated sulphuric acid from H2S. AB - Biofilters are used for the conversion of odorous hydrogen sulphide to odourless sulphate in wastewater treatment plants under the right conditions of moisture and pH. One of the consequences of maintaining the suitable pH and moisture content is the production of large volumes of weakly acidic leachate. This paper presents a biofilter with a maximum H2S elimination capacity of 16.3 g m(-3) h( 1) and removal efficiency greater than 95 % which produces small volumes (1 mL of solution L(-1) of reactor day(-1)) of sulphuric acid with a concentration greater than 5.5 M after 150 days of continuous operation. The concentrated sulphuric acid was produced by intermittently trickling a minimum amount of nutrient solution down the upflow biofilter which created a moisture and pH gradient within the biofilter resulting in an environment at the top for the bacterial conversion of H2S, while sulphuric acid was accumulated at the base. Genetic diversity profiling of samples taken from different sections of the biofilter confirms that the upper sections of the biofilter had the best environment for the bacteria to convert H2S to sulphate. The formation of concentrated sulphuric acid presents an opportunity for the recovery of sulphur from the waste stream as a usable product. PMID- 27189452 TI - Effect of operation parameters on the flux stabilization of gravity-driven membrane (GDM) filtration system for decentralized water supply. AB - A pilot-scale gravity-driven membrane (GDM) filtration system under low gravitational pressure without any pre-treatment, backwash, flushing, or chemical cleaning was carried out to investigate the effect of operation parameters (including operation pressure, aeration mode, and intermittent filtration) on the effluent quality and permeability development. The results revealed that GDM system exhibited an efficient performance for the removal of suspended substances and organic compounds. The stabilization of flux occurred and the average values of stable flux were 6.6, 8.1, and 8.6 Lm(-2) h(-1) for pressures of 65, 120, and 200 mbar, respectively. In contrast, flux stabilization was not observed under continuous and intermittent aeration conditions. However, aeration (especially continuous aeration) was effective to improve flux and alleviate membrane fouling during 1-month operation. Moreover, intermittent filtration would influence the stabilization of permeate flux, resulting in a higher stable flux (ranging from 6 to 13 Lm(-2) h(-1)). The stable flux significantly improved with the increase of intermittent period. Additionally, GDM systems exhibited an efficient recovery of flux after simple physical cleaning and the analyses of resistance reversibility demonstrated that most of the total resistance was hydraulic reversible resistance (50-75 %). Therefore, it is expected that the results of this study can develop strategies to increase membrane permeability and reduce energy consumption in GDM systems for decentralized water supply. PMID- 27189454 TI - Active biomonitoring of palladium, platinum, and rhodium emissions from road traffic using transplanted moss. AB - The use of transplanted moss (Pleurozium schreberi) in active biomonitoring of traffic-related emissions of Pd, Pt, and Rh was studied. Moss mats were transplanted to three locations along highway E75 (in Oulu, Finland) at three different distances from the highway. Five samples were collected from a background site after the same exposure period. Mass fractions of Pd, Pt, and Rh as well as mass fractions of 18 other elements were determined in these samples. The results indicated that P. schreberi is well suited for active biomonitoring of Pd, Pt, and Rh. Mass fractions above the background values were observed in the samples exposed to traffic-related emissions. When the results were compared with those of the other elements, high correlations of Pd, Pt, and Rh with commonly traffic-related elements (e.g., Cu, Ni, Sb, Zn, etc.) were found. It was also found that the amounts of Pd, Pt, and Rh in moss samples decreased when the distance to the highway increased. This trend gives evidence for the suitability of P. schreberi for active biomonitoring of Pd, Pt, and Rh. Furthermore, it can be concluded that the mass fractions determined in this study provide valuable evidence about the current state of Pd, Pt, and Rh emissions in Oulu, Finland. PMID- 27189455 TI - Elongator Protein 3 (Elp3) stabilizes Snail1 and regulates neural crest migration in Xenopus. AB - Elongator protein 3 (Elp3) is the enzymatic unit of the elongator protein complex, a histone acetyltransferase complex involved in transcriptional elongation. It has long been shown to play an important role in cell migration; however, the underlying mechanism is unknown. Here, we showed that Elp3 is expressed in pre-migratory and migrating neural crest cells in Xenopus embryos, and knockdown of Elp3 inhibited neural crest cell migration. Interestingly, Elp3 binds Snail1 through its zinc-finger domain and inhibits its ubiquitination by beta-Trcp without interfering with the Snail1/Trcp interaction. We showed evidence that Elp3-mediated stabilization of Snail1 was likely involved in the activation of N-cadherin in neural crest cells to regulate their migratory ability. Our findings provide a new mechanism for the function of Elp3 in cell migration through stabilizing Snail1, a master regulator of cell motility. PMID- 27189457 TI - Prognostic implications of reproductive and lifestyle factors in ovarian cancer. AB - INTRODUCTION: Despite strides in identifying factors that predict risk of ovarian cancer and improvements in ovarian cancer treatment, little is known about factors that predict ovarian cancer survival. METHODS: We reviewed the literature for analyses of factors before, at, or after diagnosis that may predict survival outcomes, including demographics (e.g., age and race), genetics (e.g., inherited BRCA mutations), hormonal factors (e.g., parity and hormone use), and lifestyle (e.g., physical activity and diet). RESULTS: While treatment factors, tumor characteristics and genetic syndromes are predictive of survival, few studies of most hormonal and lifestyle factors have been published; most have evaluated pre diagnosis factors. For example, we identified eight studies that examined menopausal hormone use prior to diagnosis, reporting a non-significant survival benefit for users compared to non-users, while four studies reported better survival with use after surgery, though only two were significant. Similarly, while increased body size has been extensively studied as potentially associated with reduced survival, other modifiable factors, such as diet and physical activity remain understudied. We identified three studies of pre-diagnosis physical activity and five studies of pre-diagnosis diet, with a suggestive benefit of higher vegetable intake and vigorous physical activity. By contrast, large studies of the impact of race/ethnicity and socioeconomic status (SES) confirm that non-white women and women of lower SES fare more poorly than white women and women of higher SES, respectively. CONCLUSIONS: Our review of the published literature on predictors of ovarian cancer survival revealed that modifiable lifestyle factors may be related to survival, but that hormonal factors do not strongly predict outcomes in ovarian cancer patients. However, more attention should be paid to women's post-diagnosis survival experience. The dearth of literature on post-diagnosis factors that may improve outcomes makes it difficult to make specific recommendations for survivors. PMID- 27189456 TI - Cited rationale for variance in the use of primary intraperitoneal chemotherapy following optimal cytoreduction for stage III ovarian carcinoma at a high intraperitoneal chemotherapy utilization center. AB - OBJECTIVE: Studies have demonstrated improved ovarian cancer survival with the administration of a combination of intravenous (IV) and intraperitoneal (IP) chemotherapy following optimal cytoreduction. Despite this, IV/IP chemotherapy is not uniformly used. In this retrospective cohort study, we assessed the documented reasons for giving IV-only chemotherapy. METHODS: All patients who had optimal primary cytoreductive surgery for stage III ovarian, fallopian tube, or primary peritoneal carcinoma, met eligibility criteria for GOG-172, and received primary chemotherapy at our institution between 2006 and 2013 were identified. Patients who received at least one cycle of adjuvant IV/IP therapy were included in the IP group. Patient characteristics, treatment information, and reason cited for not administering IP therapy were collected. RESULTS: Of the patients evaluated, 330 met inclusion criteria. The majority (n=261, 79%) received at least one IV/IP cycle (median, 6; range, 1-6), and 62% completed 6cycles. The most common reason for giving IV-only therapy was postoperative status (i.e., delayed wound healing, performance status), accounting for 18 (26%) of the 69 IV only patients (5% of the entire cohort). Other cited reasons were baseline comorbidities (15%) and IP port complications (12%). Receipt of >=1cycle of IP chemotherapy (HR 0.51; 95% CI, 0.32-0.80) and no gross residual disease (HR 0.47; 95% CI, 0.31-0.71) were associated with improved overall survival. CONCLUSION: Potentially modifiable factors identified as leading to the use of IV-only chemotherapy were postoperative status and IP port complications, which if altered, could potentially lead to increased IP chemotherapy use. PMID- 27189458 TI - Choroidal Thickness Changes After Intravitreal Ranibizumab for Exudative Age Related Macular Degeneration. AB - BACKGROUND: The results regarding changes of choroidal thickness following intravitreal ranibizumab injections in the literature are controversial. Vascular endothelial growth factor A is implicated in pathogenesis of neovascular age related macular degeneration (AMD). The suspected unchanged choroidal layer thickness after intravitreal injections of ranibizumab suggests a possible protection of the outer blood-retinal barrier in the human eye. OBJECTIVE: The aim was to evaluate choroidal thickness following the first administration of the study drug ranibizumab into the eyes of naive wet AMD patients (nAMD). METHODS: In this open label, 3-month, prospective, single-center, interventional, single arm pilot study, 20 nAMD eyes were included and underwent three consecutive monthly injections of ranibizumab (0.5 mg/0.05 ml). Vital signs (i.e., blood pressure and pulse), ophthalmic examinations, intraocular pressure, best correct visual acuity and subfoveal choroidal thickness as examined with optical coherence tomography using enhanced depth imaging (OCT-EDI) were assessed at each visit. All patients were evaluated at baseline and at 15, 30 60 and 90 days after intravitreal injection. Ten eyes with fibrotic AMD lesions were evaluated as the control group. RESULTS: In all eyes, the choroidal thicknesses (um) exhibited no significant changes from the baseline visit to the visits at 15, 30, 60 and 90 days post-injection (P > 0.05). The intravitreal treatment with ranibizumab was well tolerated, and no adverse events were registered. CONCLUSION: Choroidal thickness appeared to be unmodified following the intravitreal injection of ranibizumab into nAMD eyes. Intravitreal ranibizumab injections probably elicit a pharmacologic effect only in the choroidal neovascularization and not in the choroid circulation under neovascular lesions. Clinical Trials Eudract Registration #: 2013-005091-17. PMID- 27189459 TI - Shingles (Herpes Zoster) Vaccine (Zostavax((r))): A Review in the Prevention of Herpes Zoster and Postherpetic Neuralgia. AB - Zostavax((r)) is a live attenuated shingles (herpes zoster) vaccine approved in the EU for the prevention of herpes zoster (HZ) and postherpetic neuralgia (PHN) in adults aged >=50 years. Zoster vaccine protected against HZ in adults aged 50 59 years (ZEST trial) and >=60 years [Shingles Prevention Study (SPS)], and also reduced the burden of illness associated with HZ and the risk of PHN in adults aged >=60 years (SPS). A large amount of real-world data also supports the efficacy of zoster vaccine. Results of the SPS Short- and Long-Term Persistence Substudies and real-world studies indicate that zoster vaccine provided continued benefit in the longer term, albeit with a gradual decline in vaccine efficacy over time; long-term effectiveness studies are ongoing. The need for a booster dose is still unknown, but a study showed that, if necessary, a booster dose administered to adults aged >=70 years who received their first dose of zoster vaccine >=10 years previously was immunogenic. Zoster vaccine had a favourable safety and tolerability profile, with the most commonly reported adverse events being non-severe injection-site reactions. In conclusion, zoster vaccine reduces the incidence of HZ and PHN, thereby reducing the burden of illness associated with HZ; improved uptake of zoster vaccine is needed. PMID- 27189460 TI - Spontaneous Left Renal Subcapsular Hematoma and Right Hip Hematoma in a Hemodialysis Patient: A Case Report and Review of the Literature. AB - For maintenance hemodialysis (MHD) patients, the blood is in low hypercoagulable state due to the use of heparin or low molecular weight heparin during dialysis. It is not rare to see hematoma in the puncture site. In recent years, several cases have been reported of spontaneous kidney rupture, but no hip hematoma, let alone both occurred in succession. There was one MHD patient with spontaneous kidney bleeding and hip hematoma in our hospital in 2014, and we provided effective treatment and follow-up. PMID- 27189461 TI - Pepsin is a positive regulator of Ac-cathB-2 involved in the rat gut penetration of Angiostrongylus cantonensis. AB - BACKGROUND: Angiostrongyliasis caused by the rat lungworm, Angiostrongylus cantonensis (A. cantonensis), has globally spread from the traditional epidemic areas. The small intestine is the site where the third-stage larvae (L3) of this worm entered the host body, and parasite proteases are involved in this process. Ac-cathB-2, a cathepsin B-like cysteine of A. cantonensis, was formerly isolated from the insoluble part of fragmentised Escherichia coli without activity. The unplanned low activity of prokaryotic expression proteins and difficulties in genetic modification hindered understanding the function of this protein. METHODS: The recombinant Ac-cathB-2 was expressed and harvested from 293 T cells and the enzymatic property and the effects of processing on the activity of the recombinant protease were investigated in vitro. The expression of Ac-cathB-2 in response to external stimulation was assessed, and the function of this protease during host gut penetration was observed by using antiserum for inhibition. RESULTS: Of the life-cycle stages studied, L3 expressed the highest level of Ac cathB-2 gene and released the corresponding gene product from the body. The expression of this gene was rapidly upregulated after incubating L3 in small intestine homogenate of rat. Recombinant Ac-cathB-2 was harvested from 293 T cell culture medium. This protease was activated by pepsin-HCl and the enabled Ac cathB-2 could subsequently digest laminin and fibronectin readily. Moreover, the small intestine isolated from rat was disrupted after incubating with the activated Ac-cathB-2, resulting in the detachment of epithelial cells. Antiserum treatment inhibited the hydrolytic ability of recombinant Ac-cathB-2 by 82.7 %, and also reduced the tissue penetration of activated L3 by 41.2 %. Additionally, pre-incubation of L3 with artificial gastric acid increased the number of penetrating larvae by 53.2 %, and this alteration could be partly blocked by antiserum treatment. CONCLUSION: We believe that Ac-cathB-2 from A. cantonensis might help the worm to penetrate the rat gut, because the protease was able to degrade the tissue components of host. Nevertheless, our results further indicated that host pepsin played a beneficial role in this process by cleaving Ac-cathB-2 for activation. Thus, Ac-cathB-2 may probably represent an important target for the control of A. cantonensis infection. PMID- 27189463 TI - Neurobehavioral and Cognitive Changes Induced by Sleep Deprivation in Healthy Volunteers. AB - To this day, the pharmacological treatment of Alzheimer's disease remains limited to the temporary stabilisation of cognitive decline and the reduction of neuropsychiatric symptoms. It is moreover with great difficulty to predict and select promising drug candidates in the early stages of the discovery and developmental process. In this context, scientists have developed new experimental paradigms to artificially induce transient cognitive impairments in healthy volunteers akin to those observed in Alzheimer's disease, i.e. the Cognitive Challenge Models. In the last decade, a great amount of literature on Sleep Deprivation was published which mainly focused on the consequences of sleep loss for public health. However, sleep deprivation paradigm may also be regarded as a cognitive challenge model. It is commonly accepted that sleep deprivation induces cognitive impairments related to a global decrease in vigilance, while in fact, there is a controversial approach related to the selective effects on cognitive functions. The identification and validation of cognitive challenge models in healthy volunteers are suitable in early clinical development of drugs to determine the 'hint of efficacy' of drug candidates. The present review aims at exploring in detail the methods, designs and cognitive paradigms used in non pharmacological sleep deprivation studies. Sleep deprivation can be induced by different methods. Probing the four main cognitive functions will allow identifying the extent to which different sleep deprivation designs selectively compromise executive function, working memory, episodic memory and attention. Findings will be discussed in line with cognitive processing levels that are required according to the tasks. PMID- 27189462 TI - Primary and tertiary health professionals' views on the health-care of patients with co-morbid diabetes and chronic kidney disease - a qualitative study. AB - BACKGROUND: Health-care for co-morbid diabetes and chronic kidney disease (CKD) is often sub-optimal. To improve health-care, we explored the perspectives of general practitioners (GPs) and tertiary health-care professionals concerning key factors influencing health-care of diabetes and CKD. METHODS: A total of 65 health professionals were purposively sampled from Australia's 2 largest cities to participate in focus groups and semi-structured interviews. Four focus groups were conducted with GPs who referred to 4 tertiary health services in Australia's 2 largest cities, with 6 focus groups conducted with tertiary health-care professionals from the 4 tertiary health services. An additional 8 semi structured interviews were performed with specialist physicians who were heads of diabetes and renal units. All discussions were facilitated by the same researcher, with discussions digitally recorded and transcribed verbatim. All qualitative data was thematically analysed independently by 2 researchers. RESULTS: Both GPs and tertiary health-care professionals emphasised the importance of primary care and that optimal health-care was an inter-play between patient self-management and primary health-care, with specialist tertiary health care support. Patient self-management, access to specialty care, coordination of care and a preventive approach were identified as key factors that influence healthcare and require improvement. Both groups suggested that an integrated specialist diabetes-kidney service could improve care. Unit heads emphasised the importance of quality improvement activities. CONCLUSIONS: GPs and tertiary health-care professionals emphasised the importance of patient self-management and primary care involvement in the health-care of diabetes and CKD. Supporting GPs with an accessible, multidisciplinary diabetes-renal health service underpinned by strong communication pathways, a preventive approach and quality improvement activities, may improve health-care and patient outcomes in co-morbid diabetes and CKD. PMID- 27189465 TI - Early Development of Symptomatic Drugs in AD: A Systematic Review of the Use of Biomarkers. AB - Pharmacological therapies currently marketed for Alzheimer's disease (AD) are only symptomatic and show limited effects in terms of clinical benefit. Thus, the development of new symptomatic drugs remains essential. However the dramatic increase in costs associated with drug development together with the poor number of emerging drugs highlights how crucial it is to accelerate the findings aiming to bringing new drugs to market. In this respect, optimization of the development process by integrating, at early stage, reliable biomarkers able to predict clinical benefit in phase III clinical trials may help. The improvement of certain techniques such as imaging and electrophysiological methods has led to a more accurate assessment of the brain's physiological impact of pharmacological treatments used to alleviate symptoms in AD patients. This review aims to gather the main findings from clinical studies where the effect of anti-dementia drugs were assessed in healthy volunteers and AD patients through one or several such biomarkers (electroencephalography (EEG), magnetic resonance imaging (MRI), positron emission tomography (PET), single-photon emission computed tomography (SPECT)). Overall, evidence presented in this review suggests that various biomarkers associated with key impairments observed in AD were sensitive to acetylcholinesterase inhibitors (AChE-I) medication and memantine with a good correlation with enhancement of cognitive performance. In most of the reviewed studies, only one kind of biomarker was used. Among these, deficits in quantitative EEG profile, P300 latency, and regional brain activity measured by either functional MRI (fMRI) during face encoding and working memory task or by PET/SPECT have been shown to be reversed by anti-dementia drugs. It is therefore suggested that a single biomarker approach would be limited and not be sufficiently predictive to extensively assess the potential of a new symptomatic drug. Hence, it appears that a combination approach with the use of a panel of biomarkers rather than a single biomarker may be more appropriate to establish a good correlation between the disease and therapeutic intervention. PMID- 27189464 TI - Translational Challenge Models in Support of Efficacy Studies: Effect of Cerebral Hypoxia on Cognitive Performances in Rodents. AB - Empirical evidence currently supports the idea that neurovascular dysfunction is involved in the neurodegenerative process of Alzheimer's disease (AD). In fact, epidemiological studies report that i) vascular risk factors are directly associated with an increased incidence of AD and ii) vascular lesions are frequently co-existent with AD. The neurovascular unit is a key control system for oxygen and nutrients exchange between neurons and microvessels so the integrity of this system is essential for neuronal activity and cell survival. This suggests that hypoxia arising from various vascular injuries may participate in the pathogenesis of AD and aggravate cognitive deficit. Moreover, hypoxia appears to have a direct effect on cognitive functions, in particular memory, by inducing a transient or definitive dysfunction of synaptic transmission. The interplay of hypoxic phenomenon and the development of AD-related pathologies support the use of hypoxia as a challenge model to assess symptomatic (i.e. cognitive enhancers) AD-treatment. Such challenge should be characterized and validated with current symptomatic drugs based on different mechanisms of action before being offered as alternative models for testing new drugs. To date, symptomatic treatments of AD including anticholinesterasic- (donepezil, rivastigmine and galantamine) and antiglutamatergic- (memantine) drugs target various neurotransmission impairments occurring at different stages of the disease. The first aim of the present review is to provide an overview of the methods used to achieve experimental hypoxia in rodents and to characterize the cognitive alterations induced by each method. The second objective is to summarize the main results from studies that have tested the effect of acetylcholinesterase inhibitors on hypoxiainduced cognitive impairment. Overall, the literature research yielded only a small number of studies investigating the effect of hypoxia on cognition in rodents and the different models described sometime differ substantially in terms of timing, severity and nature of cognitive impairment. Chronic exposure to intermittent normobaric or continuous hypobaric hypoxia induced persistent spatial reference and working memory alterations. In contrast, acute hypoxia exposure was shown to induce more transient associative and spatial memory impairments. Treatment with acetylcholinesterase inhibitors was shown to improve hypoxia-induced memory impairment in various hypoxia protocols. PMID- 27189466 TI - Translational Challenge Models in Support of Efficacy Studies: Neurobehavioral and Cognitive Changes Induced by Transcranial Magnetic Stimulation in Healthy Volunteers. AB - Transcranial Magnetic Stimulation (TMS) was proposed as a neurophysiological tool almost three decades ago. It now encompasses a very wide range of applications including clinical research and the treatment of psychiatric, neurologic and medical conditions such as depression, schizophrenia, addictions, post-traumatic stress disorders, pain, migraine, stroke, Alzheimer's disease, autism, multiple sclerosis and Parkinson's disease. By inducing electrical brain responses through the administration of magnetic pulses, TMS is in a unique position to painlessly modulate cortical regions and offers good spatial resolution and excellent temporal resolution, particularly when applied using single pulses. However, despite the impressive number of papers describing the use of TMS to modulate cognitive functions, the mechanisms underlying the behavioral changes observed after stimulation have not been fully identified. Here we present a review of the ability of TMS to transiently compromise brain function in humans. The primary aim was to investigate its capacity for use as a 'cognitive challenge model' in human pharmacological studies. The data reviewed include findings on executive function, attention and episodic memory. For each cognitive process, the convergent and divergent results are discussed in terms of paradigm differences and in order to define the optimal methodology for obtaining the desired effects. PMID- 27189467 TI - Emerging Risk Factors for Dementia: The Role of Blood Pressure Variability. AB - In the recent years, classical vascular risk factors have been suggested to play a role also in the development of degenerative dementia. Arterial hypertension has been implicated in the pathogenesis of dementia but no conclusive results have been produced yet; more recently, blood pressure variability (BPV) has been suggested as a more important risk factor for both silent brain vascular lesions and the development of dementia. Blood pressure variability is defined as the variation in blood pressure over time, measured on different time spans and in different ways. We reviewed current scientific literature about the role of BPV in the pathogenesis of dementia, and about the association of abnormal BPV patterns and different forms of dementia. We also suggested some hypothetical pathogenic mechanisms. PMID- 27189468 TI - Obstructive Sleep Apnea Syndrome: An Emerging Risk Factor for Dementia. AB - Epidemiological studies have suggested that obstructive sleep apnea syndrome (OSAS) may increase the risk of developing cognitive impairment. In patients with Alzheimer's disease (AD), the prevalence of OSAS is much higher than that expected in cognitively healthy subjects. A deeper knowledge of the pathophysiological link between OSAS and AD and the demonstration that OSAS may directly influence the development of cognitive alterations, would increase prevention and treatment strategies for AD patients. In this article, we discuss the evidence of the association between OSAS and dementia. Moreover, we present data about the functional and anatomic cerebral changes induced by OSAS and the possible effects on cognitive activities and on AD pathogenesis. The possibility to positively influence cognitive impairment by OSAS treatment will be also discussed. PMID- 27189469 TI - Targeting New Pharmacological Approaches for Alzheimer's Disease: Potential for Statins and Phosphodiesterase Inhibitors. AB - Alzheimer's disease (AD) is the most common cause of dementia among the elderly. It is pathologically characterized by diffused extracellular deposits, senile plaques, and intracellular neurofibrillary tangles in the brain, responsible for neuronal dysfunction and cell death. Memory, language and other cognitive functions can be affected to a limited extent in the initial stage called mild cognitive impairment (MCI) or in a more severe and daily life interfering manner in the later stage called dementia. Currently no effective disease-modifying treatment exists for the majority of neurodegenerative diseases. Failure of therapy aimed at affecting beta amyloid pathology has led research to investigate alternative approaches. Recent findings address statins and phosphodiesterase (PDE) inhibitors as compounds able to affect different mechanisms underlying AD. Statins could exert several effects based on their lipid-lowering and cerebral blood flow increasing abilities but also pleiotropic/antinflammatory and neuroprotective properties have been claimed. PDEs act as regulators of intracellular signaling cascades through the control of two second messengers, cyclic adenosine monophosphate and cyclic guanosine monophosphate. PDE inhibitors effects in animal models of AD have been promising and their proven safety in clinical use create high expectations for the treatment of AD. In this review, we will report main data and evidence on: 1. Current pathophysiological theories of AD in order to better understand which mechanisms lead to pathological changes and can be affected by therapies; 2. The use of statins and PDE inhibitors in animal models of AD and in humans, analyzing their mechanisms of action. PMID- 27189470 TI - Adrenergic Drugs Blockers or Enhancers for Cognitive Decline ? What to Choose for Alzheimer's Disease Patients? AB - The adrenergic system has an important role in normal central nervous system function as well as in brain disease. The locus coeruleus, the main source of norepinephrine in brain, is involved in the regulation of learning and memory, reinforcement of sleep-wake cycle and synaptic plasticity. In Alzheimer's disease, locus coeruleus degeneration is observed early in the course of the disease, years before the onset of clinical cognitive signs, with neurofibrillary detected at the stage of mild cognitive impairment, preceding amyloid deposition. Thus, in the last years, a great interest has grown in evaluating the possibility of central adrenergic system modulation as a therapeutic tool in Alzheimer's disease. However, evidences do not show univocal results, with some studies suggesting that adrenergic stimulation might be beneficial in Alzheimer's Disease and some others favoring adrenergic blockade. In this review, we summarize data from both hypothesis and describe the pathophysiological role of the adrenergic system in neurodegeneration. PMID- 27189471 TI - Insulin and the Future Treatment of Alzheimer's Disease. AB - Alzheimer's disease is a neurodegenerative disorder leading to dementia. Scientific efforts in the last decade focused mainly on understanding pathophysiology of disease and possible pharmacological approach to alleviate cognitive decline symptoms. Amyloid cascade hypothesis though criticized, remains the leading hypothesis to understand pathogenic mechanisms of cognitive decline. Intriguingly, changes of metabolic activity of cortical neurons are associated with reduced or absent sensitivity to insulin in Alzheimer's disease brain. Insulin is a multipotent hormone regulating, not only glucose levels, but also cell survival and synaptic plasticity mechanisms of neurons. Replacement of insulin might represent a new strategic approach to counteract neurodegeneration. Here we review most of the available data regarding relationship between Alzheimer's disease and insulin and propose new direction to deepen our understanding about insulin involvement in the pathogenesis of Alzheimer's dementia. PMID- 27189472 TI - Beyond Cholinesterase Inhibition: Anti-Inflammatory Role and Pharmacological Profile of Current Drug Therapy for Alzheimer's Disease. AB - Inflammation is a common response of an individual against either exogenous or endogenous damage. The role of inflammation and of inflammatory cells recently emerged also in the pathogenesis of neurodegenerative disorders. Experimental evidences show how neurotransmitters, besides their role in the synapses, play a modulatory role during immune response. Drugs used for treatment of dementia symptoms are able to increase neurotransmitters levels, and likely to have a modulatory role during immune response. Aim of this review is to discuss the most recent advances on inflammation role during neurodegeneration and also to individuate the potential anti-inflammatory role played by drugs currently used for Alzheimer's disease treatment. PMID- 27189473 TI - Molecular Mechanisms Involving Sigma-1 Receptor in Cell Apoptosis of BV-2 Microglial Cells Induced by Methamphetamine. AB - It has been well documented that methamphetamine induces microglial activation and death, however, the molecular mechanisms underlying this process remain poorly understood. In the present study, we demonstrated the involvement of sigma 1 receptor (sigma-1R) in methamphetamine-mediated microglial apoptosis. Exposure of BV-2 cells to methamphetamine induces cell apoptosis through its cognate receptor sigma-1R, followed by activation of the mitogen-activated protein kinases, phosphatidylinositol-3' kinase/Akt as well as the downstream transcription factor p53 pathways. Blockage of sigma -1R significantly inhibited the increased pro-apoptotic proteins such as Bax, Caspase-3 and Caspase-9 induced by methamphetamine. In conclusion, these findings underscore the critical role of sigma-1R in microglial apoptosis induced by methamphetamine. Understanding the link between sigma -1R and apoptosis will lead to development of therapeutic strategies targeting methamphetamine-mediated microglial death/dysfunction. PMID- 27189474 TI - Influence of Hypertension, Alone and in Combination with Other Vascular Risk Factors on Cognition. AB - Hypertension is one of the most important modifiable risk factors of cardioand cerebrovascular diseases, responsible for the development of severe target organ damages. It has been shown that hypertension is associated with an increased prevalence of cognitive decline. It negatively affects the cognitive battery and accelerates dementia. Beside the known detrimental effects of senile hypertension on cognitive performance in the elderly population, previous studies pointed out that young, hypertensive individuals may also suffer from hypertension related changes in their cognitive capacity. Given the high prevalence of hypertension in a wide range of the age pyramid (young individuals, middle aged adults, elderly people), specific cognitive deficits may be present in a large portion of the population putting a heavy burden on society. Better understanding of the underlying mechanisms of hypertension induced cognitive impairment may contribute to the identification of its initiating pathophysiological factors, and serve an earlier diagnosis, intervention at an early stage and prevention of further deficits. Our aim with the current review was to summarize some of the previous findings regarding altered cognitive performance of individuals with hypertension and of those with the most common co-existing risk factors. Furthermore, efforts to explore effects of various antihypertensive medications on cognition and to survey proposed pathophysiological mechanisms of hypertension induced cognitive changes have been made. PMID- 27189475 TI - Paenibacillusliaoningensis sp. nov., isolated from soil. AB - A novel bacterial strain, designated as LNUB461T, was isolated from soil sample taken from the countryside of Shenyang, Liaoning Province, China. The isolate was a Gram-stain-positive, aerobiotic, motile, endospore-forming and rod-shaped bacterium. The organism grew optimally at 30-33 degrees C, pH 6.5-7.0 and in the absence of NaCl. Phylogenetic analysis based on the nearly full-length 16S rRNA gene sequence revealed high sequence similarity with Paenibacillus algorifonticola XJ259T (98.5 %), Paenibacillus xinjiangensis B538T (96.8 %), Paenibacillus glycanilyticus DS-1T (96.1 %) and Paenibacillus lupini RLAHU15T (96.1 %). The predominant cellular fatty acid and the only menaquinone were anteiso-C15:0 and MK-7, respectively. The main polar lipids of LNUB461T included phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylcholine (PC) and two unknown amino phospholipids (APL), and the cell-wall peptidoglycan was meso-diaminopimelic acid (A1gamma). The DNA G+C content of LNUB461T was 49.1 mol%. The DNA-DNA hybridization value between LNUB461T and the most closely related species (P. algorifonticola) was 41.8 %. On the basis of these data, LNUB461T was classified as representing a novel species of the genus Paenibacillus, for which the name Paenibacillus liaoningensis sp. nov was proposed. The type strain is LNUB461T (=JCM 30712T=CGMCC 1.15101T). PMID- 27189476 TI - Implementation of an educational program to decrease the tidal volume size in a general intensive care unit: a pilot study. PMID- 27189480 TI - Therapeutic hypothermia in neonatal cervical spine injury. PMID- 27189479 TI - In vitro and in vivo antineoplastic and immunological effects of pterocarpanquinone LQB-118. AB - Cancer is a malignancy of worldwide prevalence, and although new therapeutic strategies are under investigation, patients still resort to reductive or palliative chemotherapy. Side effects are a great concern, since treatment can render patients susceptible to infections or secondary cancers. Thus, design of safer chemotherapeutic drugs must consider the risk of immunotoxicity. Pterocarpans are natural isoflavones that possess immunomodulatory and antineoplastic properties. Ubiquitous in nature, quinones are present in chemotherapeutic drugs such as doxorubicin and mitoxantrone. Our group has patented a hybrid molecule, the pterocarpanquinone LQB-118, and demonstrated its antineoplastic effect in vitro. In this report we describe its antineoplastic effect in vivo and assess its toxicity toward the immune system. Treated mice presented no changes in weight of primary and secondary organs of the immune system nor their cellular composition. Immunophenotyping showed that treatment increased CD4(+) thymocytes and proportionally reduced the CD4(+)CD8(+) subpopulation in the thymus. No significant changes were observed in T CD8(+) peripheral lymphocytes nor was the activation of fresh T cells affected after treatment. LQB-118 induced apoptosis in murine tumor cells in vitro, being synergistic with the autophagy promoter rapamycin. Furthermore, treatment significantly reduced ascites or solid Ehrlich and B16F10 melanoma growth in vivo, and ameliorated side effects such as cachexia. Based on its favorable preclinical profile and considering previous results obtained in vitro, this drug emerges as a promising candidate for further development. PMID- 27189477 TI - The Fas Ligand/Fas Death Receptor Pathways Contribute to Propofol-Induced Apoptosis and Neuroinflammation in the Brain of Neonatal Rats. AB - A number of experimental studies have reported that exposure to common, clinically used anesthetics induce extensive neuroapoptosis and cognitive impairment when applied to young rodents, up to 2 weeks old, in phase of rapid synaptogenesis. Propofol is the most used general anesthetic in clinical practice whose mechanisms of neurotoxicity on the developing brain remains to be examined in depth. This study investigated effects of different exposures to propofol anesthesia on Fas receptor and Fas ligand expressions, which mediate proapoptotic and proinflammation signaling in the brain. Propofol (20 mg/kg) was administered to 7-day-old rats in multiple doses sufficient to maintain 2-, 4- and 6-h duration of anesthesia. Animals were sacrificed at 0, 4, 16 and 24 h after termination of anesthesia. It was found that propofol anesthesia induced Fas/FasL and downstream caspase-8 expression more prominently in the thalamus than in the cortex. Opposite, Bcl-2 and caspase-9, markers of intrinsic pathway activation, were shown to be more influenced by propofol treatment in the cortex. Further, we have established upregulation of caspase-1 and IL-1beta cytokine transcription as well as subsequent activation of microglia that is potentially associated with brain inflammation. Behavioral analyses revealed that P35 and P60 animals, neonatally exposed to propofol, had significantly higher motor activity during three consecutive days of testing in the open field, though formation of the intersession habituation was not prevented. This data, together with our previous results, contributes to elucidation of complex mechanisms of propofol toxicity in developing brain. PMID- 27189478 TI - Pro-apoptotic Action of Corticosterone in Hippocampal Organotypic Cultures. AB - Elevated levels of glucocorticoids exert neurotoxic effects, and the hippocampus is particularly sensitive to the effects of glucocorticoids. Because some data have indicated that an increased action of glucocorticoids in the perinatal period enhances the susceptibility of brain tissue to adverse substances later in life, the main purpose of the present study was to compare necrotic/apoptotic corticosterone action in hippocampal organotypic cultures obtained from control animals with the effect of this steroid in tissue from prenatally stressed rats. Because the adverse effects of glucocorticoid action on nerve cell viability appear to result mainly from an increase in the intensity of the effects of glutamate and changes in growth factor and pro-inflammatory cytokine synthesis, the involvement of these factors in corticosterone action were also determined. In stress-like concentration (1 MUM), corticosterone, when added to hippocampal cultures for 1 and 3 days, alone or jointly with glutamate, did not induce necrosis. In contrast, in 3-day cultures, corticosterone (1 MUM) increased caspase-3 activity and the mRNA expression of the pro-apoptotic Bax. Moreover, corticosterone's effect on caspase-3 activity was stronger in hippocampal cultures from prenatally stressed compared to control rats. Additionally, 24 h of exposure to corticosterone and glutamate, when applied separately and together, increased Bdnf, Ngf, and Tnf-alpha expression. In contrast, after 72 h, a strong decrease in the expression of both growth factors was observed, while the expression of TNF-alpha remained high. The present study showed that in stress like concentrations, corticosterone exerted pro-apoptotic but not necrotic effects in hippocampal organotypic cultures. Prenatal stress increased the pro apoptotic effects of corticosterone. Increased synthesis of the pro-inflammatory cytokine TNF-alpha may be connected with the adverse effects of corticosterone on brain cell viability. PMID- 27189481 TI - Gene evolution and gene expression after whole genome duplication in fish: the PhyloFish database. AB - With more than 30,000 species, ray-finned fish represent approximately half of vertebrates. The evolution of ray-finned fish was impacted by several whole genome duplication (WGD) events including a teleost-specific WGD event (TGD) that occurred at the root of the teleost lineage about 350 million years ago (Mya) and more recent WGD events in salmonids, carps, suckers and others. In plants and animals, WGD events are associated with adaptive radiations and evolutionary innovations. WGD-spurred innovation may be especially relevant in the case of teleost fish, which colonized a wide diversity of habitats on earth, including many extreme environments. Fish biodiversity, the use of fish models for human medicine and ecological studies, and the importance of fish in human nutrition, fuel an important need for the characterization of gene expression repertoires and corresponding evolutionary histories of ray-finned fish genes. To this aim, we performed transcriptome analyses and developed the PhyloFish database to provide (i) de novo assembled gene repertoires in 23 different ray-finned fish species including two holosteans (i.e. a group that diverged from teleosts before TGD) and 21 teleosts (including six salmonids), and (ii) gene expression levels in ten different tissues and organs (and embryos for many) in the same species. This resource was generated using a common deep RNA sequencing protocol to obtain the most exhaustive gene repertoire possible in each species that allows between species comparisons to study the evolution of gene expression in different lineages. The PhyloFish database described here can be accessed and searched using RNAbrowse, a simple and efficient solution to give access to RNA-seq de novo assembled transcripts. PMID- 27189483 TI - Debriefing practices in interprofessional simulation with students: a sociomaterial perspective. AB - BACKGROUND: The debriefing phase is an important feature of simulation activities for learning. This study applies a sociomaterial perspective on debriefing in interprofessional simulation with medical and nursing students. Sociomaterial perspectives are increasingly being used in order to understand professional practice and learning in new ways, conceptualising professional practice as being embodied, relational and situated in sociomaterial relations. The aim of the study is to explore how debriefing is carried out as a practice supporting students' interprofessional learning. METHODS: Eighteen debriefing sessions following interprofessional full-scale manikin-based simulation with nursing and medical students from two different universities were video-recorded and analysed collaboratively by a team of researchers, applying a structured scheme for constant comparative analysis. RESULTS: The findings show how debriefing is intertwined with, and shaped by social and material relationships. Two patterns of enacting debriefing emerged. Debriefing as algorithm was enacted as a protocol based, closed inquiry approach. Debriefing as laissez-faire was enacted as a loosely structured collegial conversation with an open inquiry approach. CONCLUSION: The findings indicate that neither an imposed structure of the debriefing, nor the lack of structure assured interprofessional collaboration to emerge as a salient topic for reflection, even though that was an explicit learning objective for the simulation. PMID- 27189482 TI - Impaired longitudinal deformation measured by speckle-tracking echocardiography in children with end-stage renal disease. AB - BACKGROUND: Left ventricular dysfunction is an important co-morbidity of end stage renal disease (ESRD) and is associated with a poor prognosis in the adult population. In pediatric ESRD, left ventricular function is generally well preserved, but limited information is available on early changes in myocardial function. The aim of this study was to investigate myocardial mechanics in pediatric patients with ESRD using speckle-tracking echocardiography (STE). METHODS: Echocardiographic studies, including M-mode, tissue Doppler imaging (TDI) and STE, were performed in 19 children on dialysis, 17 transplant patients and 33 age-matched controls. Strain measurements were performed from the apical four-chamber and the short axis view, respectively. RESULTS: The interventricular and left ventricular posterior wall thickness was significantly increased in dialysis and transplant patients compared to healthy controls. No significant differences were found in shortening fraction, ejection fraction and systolic tissue Doppler velocities. Dialysis and transplant patients had a decreased mean longitudinal strain compared to healthy controls, with a mean difference of 3.1 [95 % confidence interval (CI) 2.0-4.4] and 2.7 (95 % CI 1.2-4.2), respectively. No differences were found for radial and circumferential strain. CONCLUSIONS: Speckle-tracking echocardiography may reveal early myocardial dysfunction in the absence of systolic dysfunction measured by conventional ultrasound or TDI in children with ESRD. PMID- 27189484 TI - Aromatic Surfactant as Aggregating Agent for Aptamer-Gold Nanoparticle-Based Detection of Plasmodium Lactate Dehydrogenase. AB - A novel ssDNA aptamer (P38), with a 40 mer random region flanked by primer binding sites on both sides, targeting Plasmodium falciparum lactate dehydrogenase (PfLDH) has been developed through systematic evolution of ligands by exponential enrichment (SELEX), including counter SELEX against human lactate dehydrogenase A and B (hLDH A and B). The 2D structure of P38 shows the presence of three stem loops with a deltaG of -9.18 kcal/mol. EMSA studies on P38 complexes with the increasing concentration of PfLDH revealed a dissociation constant of 0.35 uM. P38 has been exploited for the quantitative detection of PfLDH using cationic surfactant-mediated aggregation of gold nanoparticles (16-nm diameter) as an optical probe. Among the three different cationic surfactants, characterized by different hydrocarbon tail groups, benzalkonium chloride (BCK) was found to be most efficient with a limit of detection of 281 +/- 11 pM. This BCK-based approach with the novel highly selective aptamer provides simple and sensitive detection of PfLDH in the clinically relevant range. PMID- 27189486 TI - Smoke-Free Multi-unit Housing Policies Show Promise in Reducing Secondhand Smoke Exposure Among Racially and Ethnically Diverse, Low-Income Seniors. AB - Secondhand smoke (SHS) exposure is a public health issue for residents of multi unit housing (MUH) properties. We evaluated the impact of smoke-free policy implementation on reported SHS exposure among racially, ethnically diverse seniors living in low-income MUH properties. In Spring 2013 and Summer 2014, we surveyed residents (n = 960) at 15 MUH properties in Broward and Miami-Dade Counties, Florida. The percentage of residents reporting SHS exposure within their apartments from elsewhere in or around their building decreased from 31.1 %, before policy implementation, to 23.6 % at follow-up (p = 0.02). In multivariate analysis of non-smoking residents after policy implementation, residents who reported having one or more comorbidities were two times more likely to report SHS exposure (aOR 2.23, 95 % CI 1.12-4.40). Considering the vulnerability of low-income seniors to SHS exposure, our findings are relevant to residents, property owners/managers, and public health professionals making decisions about smoke-free policies for MUH properties in which seniors reside. PMID- 27189485 TI - Long-term clinical and echocardiographic outcomes of extensive septal myectomy for hypertrophic obstructive cardiomyopathy in Chinese patients. AB - BACKGROUND: There has been limited data addressing outcomes of extensive septal myectomy in Chinese patients with hypertrophic obstructive cardiomyopathy (HOCM). In this study, the objective was to evaluate the clinical and echocardiographic outcomes of extensive septal myectomy in a relative large number of Chinese HOCM patients over long-term follow-up. METHODS: We retrospectively studied 139 consecutive HOCM patients (age 43 +/- 15 years, 37 % male) who underwent extensive left ventricular septal myectomy. During the perioperative period, all patients were examined by echocardiography. All-cause death and cardiac death were considered as primary endpoints during follow-up. Perioperative data was obtained by retrospective review of institutional surgical databases. Follow-up data of echocardiography and clinical status was recorded through outpatient interview. RESULTS: Perioperative events consisted of arrhythmia, retraction injury to aortic valve leaflets, pleural effusion, and hemodialysis and the use of intra-aortic balloon pump. There was no in-hospital mortality. The follow-up period averaged 5.6 +/- 0.9 years and overall survivals were 100.0, 99.3, 99.3, 98.5 and 97.8 % at 1, 2, 3, 4 and 5 years, respectively. Left ventricular outflow tract (LVOT) gradient decreased form preoperative 84 +/- 17 mmHg to 12 +/- 3 mmHg at 2.5 years after surgery and it further reduced to 6 +/- 3 mmHg at 5 years after surgery (P < 0.05). Compared with the preoperative levels, interventricualr septal thickness decreased by 32 % while diastole left ventricular inner diameter approximately increased by 10 % and ejection fraction (EF) was significantly elevated during follow-up (P < 0.05). By echocardiography detection, mitral regurgitation was ameliorated for HOCM patients after surgery. There was significant improvement in New York Heart Association (NYHA) class. The proportion of NYHA III and IV decreased from preoperative 58 to 19 % at 2.5 years after surgery and it reduced to 11 % at 5 years after operation. CONCLUSION: Extensive septal myectomy offers minimal operative risk and provides long-term relief for LVOT obstruction in Chinese HOCM patients. PMID- 27189487 TI - Erratum to: Appearances of screen-detected versus symptomatic colorectal cancers at CT colonography. PMID- 27189488 TI - Magnetic resonance angiography of fetal vasculature at 3.0 T. AB - : Magnetic resonance angiography has not been used much previously for visualizing fetal vessels in utero for reasons that include a contraindication for the use of exogenous contrast agents, maternal respiratory motion and fetal motion. In this work, we report the feasibility of using an appropriately modified clinical time-of-flight magnetic resonance imaging sequence for non contrast angiography of human fetal and placental vessels at 3.0 T. Using this 2D angiography technique, it is possible to visualize fetal vascular networks in late pregnancy. KEY POINTS: * 3D-visualization of fetal vasculature is feasible using non-contrast MRA at 3.0 T. * Visualization of placental vasculature is also possible with this method. * Fetal MRA can serve as a vascular localizer for quantitative MRI studies. * This method can be extended to 1.5 T. PMID- 27189489 TI - Purification and characterization of two-domain glutaredoxin in the parasitic helminth Fasciola gigantica. AB - Glutaredoxins (Grxs) are small thiol-dependent proteins and key elements of redox signaling as they regulate the redox state of important cellular proteins. In the present study, the complete sequence of a glutaredoxin protein, obtained from the liver fluke Fasciola gigantica, was PCR-amplified and cloned. The 690-bp open reading frame (ORF) encodes a 230-amino acid protein with two conserved domains (FgGrxD1 and FgGrxD2) and has similarities with two monothiol Grxs of Saccharomyces cerevisiae, i.e., ScGrx3 and ScGrx4. The full-length FgGrx along with its two constituent domains were overexpressed in Escherichia coli as hexahistidyl-tagged proteins. The affinity chromatography resulted in almost pure and soluble proteins. The full-length FgGrx and the FgGrxD2 showed reddish-brown color, indicating the presence of bound iron in the second domain. In the insulin based reduction assay, both FgGrx and FgGrxD2 containing the active site motif CGFS exhibited a weak reducing activity, whereas FgGrxD1 was inactive. Additionally, FgGrx did not show any GSH-disulfide transhydrogenase activity when 2-hydroxyethyl disulfide (HED) or de-hydroascorbate (DHA) were taken as substrates. These results indicated the probable role of FgGrx in cellular iron sulfur homeostasis. FgGrx was found to be reversibly S-glutathionylated, suggesting a potential redox regulation that is likely to take place at the active site Cys158. Since there is only one Cys in FgGrxD2, the Cys158 might be involved in FeS binding. This study is the first report on the presence of Grx in platyhelminthic parasites and provides a starting point for further characterization of the redox network in liver flukes. PMID- 27189490 TI - In vivo Real-Time Mass Spectrometry for Guided Surgery Application. AB - Here we describe a new instrument (SpiderMass) designed for in vivo and real-time analysis. In this instrument ion production is performed remotely from the MS instrument and the generated ions are transported in real-time to the MS analyzer. Ion production is promoted by Resonant Infrared Laser Ablation (RIR-LA) based on the highly effective excitation of O-H bonds in water molecules naturally present in most biological samples. The retrieved molecular patterns are specific to the cell phenotypes and benign versus cancer regions of patient biopsies can be easily differentiated. We also demonstrate by analysis of human skin that SpiderMass can be used under in vivo conditions with minimal damage and pain. Furthermore SpiderMass can also be used for real-time drug metabolism and pharmacokinetic (DMPK) analysis or food safety topics. SpiderMass is thus the first MS based system designed for in vivo real-time analysis under minimally invasive conditions. PMID- 27189491 TI - Depression and key associated factors in female sex workers and women living with HIV/AIDS in the Dominican Republic. AB - Little is known about the mental health of female sex workers and women living with HIV/AIDS in the Dominican Republic, which impedes HIV prevention, testing, and treatment. This project estimates the prevalence of depression and identifies key contributing factors to this outcome in female sex workers, women living with HIV/AIDS, and a comparison group. Participants were female sex workers (N = 349), women living with HIV/AIDS (N = 213), and a comparison group of HIV-negative women who were not sex workers (N = 314) from the Dominican Republic. Participants completed questionnaires assessing demographic characteristics and depression. Female sex workers and women living with HIV/AIDS completed additional questionnaires ascertaining HIV or sex work-related internalized stigma. Depression was prevalent among female sex workers (70.2%), women living with HIV/AIDS (81.1%), and the comparison group (52.2%). Adjusted logistic regressions showed that internalized stigma was associated with depression for female sex workers (OR = 2.73; 95% CI = 1.95-3.84) and women living with HIV/AIDS (OR = 3.06; 95% CI = 1.86-5.05). Permanent income was associated with this outcome for female sex workers (OR = 0.08; 95% CI = 0.01-0.80) and the comparison group (OR = 0.04; 95% CI = 0.00-0.45). PMID- 27189493 TI - E-cigarettes-beware of the rocket in your pocket. PMID- 27189492 TI - Growth arrest specific gene 7 is associated with schizophrenia and regulates neuronal migration and morphogenesis. AB - BACKGROUND: Schizophrenia is a highly heritable chronic mental disorder with significant abnormalities in brain function. The neurodevelopmental hypothesis proposes that schizophrenia originates in the prenatal period due to impairments in neuronal developmental processes such as migration and arborization, leading to abnormal brain maturation. Previous studies have identified multiple promising candidate genes that drive functions in neurodevelopment and are associated with schizophrenia. However, the molecular mechanisms of how they exert effects on the pathophysiology of schizophrenia remain largely unknown. RESULTS: In our research, we identified growth arrest specific gene 7 (GAS7) as a schizophrenia risk gene in two independent Han Chinese populations using a two-stage association study. Functional experiments were done to further explore the underlying mechanisms of the role of Gas7 in cortical development. In vitro, we discovered that Gas7 contributed to neurite outgrowth through the F-BAR domain. In vivo, overexpression of Gas7 arrested neuronal migration by increasing leading process branching, while suppression of Gas7 could inhibit neuronal migration by lengthening leading processes. Through a series of behavioral tests, we also found that Gas7-deficient mice showed sensorimotor gating deficits. CONCLUSIONS: Our results demonstrate GAS7 as a susceptibility gene for schizophrenia. Gas7 might participate in the pathogenesis of schizophrenia by regulating neurite outgrowth and neuronal migration through its C-terminal F-BAR domain. The impaired pre-pulse inhibition (PPI) of Gas7-deficient mice might mirror the disease-related behavior in schizophrenia. PMID- 27189494 TI - Sonidegib for the treatment of advanced basal cell carcinoma: a comprehensive review of sonidegib and the BOLT trial with 12-month update. AB - The Hedgehog inhibitors are promising alternative for patients with advanced basal cell carcinoma that are not amenable to radiotherapy or surgery. Sonidegib, also known as LDE225, is an orally available SMO antagonist that was recently approved by the US FDA for the treatment of patients with locally advanced basal cell carcinoma. This article will provide an overview of the pharmacology and pharmacokinetics of sonidegib and in-depth analysis of the BOLT trial with additional data from the 12-month update. The present challenges associated with Hedgehog inhibitors will also be discussed. PMID- 27189495 TI - Biological approach of dental caries management. AB - Dental caries is a disease induced by dental plaque, which can be described as a community of microorganisms (biofilm). Because of genetic and environmental factors a number of changes in the oral microbiome takes place; in case of commensalism and mutualism between biofilm microorganisms and the host, homeostasis in oral microbiome is maintained. However, when a risk factor occurs parasitic relationship starts prevailing and activity of the pathogenic cariogenic microorganisms increases leading to a dental caries. According to the newest technologies of molecular microbiology new cariogenic microorganisms species have been determined. Each individual's oral microbiome is as unique as his/her immune system; therefore, commonly taken caries prevention measures cannot be of the same effectiveness for all individuals. Each person has his own caries risk which is determined by the oral microbiome and immune system influenced by the environmental and genetic factors. Early caries diagnostic, risk assessment and individualized caries prevention plan will allow us to control the disease and achieve a desirable effect. For the dentist the most important thing is not to treat the consequences of the disease - cavities - but be aware of the dental caries as a biological phenomenon. PMID- 27189496 TI - Temporomandibular joint arthrocentesis for the treatment of osteoarthritis. AB - The aim of the study was to estimate the effect of arthrocentesis in the treatment of osteoarthritis of the temporomandibular joint (TMJ), evaluate and compare cytological and biochemical findings in the synovial fluid (SF) as well in venous blood samples and to determine the effectiveness of arthrocentesis with regard to TMJ pain intensity and mandibular movement. PATIENTS AND METHODS: Twenty three consecutive patients with a diagnosis of TMJ osteoarthritis (Wilkes' stages III, IV) after noneffective conservative treatment were treated with arthrocentesis using push and pull technique (Alstergren et al. 1995). Preoperative radiographs and the scores pre- and posttreatment (after 6 months), maximal interincisal opening (MIO) and visual analogue scale (VAS) for pain estimation were performed. Blocking the auriculotemporal nerve with a 2 mL of 2% lidocaine solution, the needle was inserted into the upper joint compartment and connected with the three-way stopcock for infusion therapy (Discofix(r) Braun) and 2-3 mL of saline solution was pushed slowly to the upper compartment and then aspirated back. The first SF aspirate was allocated for the following analysis: SF viscosity, presence of crystals, SF rheumatoid factor (RF) compared to blood plasma RF. The washing was repeated 3-4 times until the aspirate was clear. RESULTS: After 6 months MIO improved significantly (p<0.05) and pain according to VAS had substantially decreased (p<0.01). Viscosity of the aspirate was 0.78 (medium), crystals were found in 5 patients (21.7%). There was not statistical significant difference between SF RF and plasma RF values (p>0.05).The effectiveness of arthrocentesis may be explained by the joint space expansion achieved with the introduction fluid, washing out inflammatory mediators, the particles of adhesions, fibrillations, crystals etc. CONCLUSIONS: Arthrocentesis with this technique for the treatment of TMJ osteoarthritis offer favourable results with regard to increasing MIO, reducing pain and dysfunction. The presence of crystals or chondromatosis granules in the synovial fluid and increased viscosity of the synovial fluid indicates a pathological condition of an inflammatory nature. PMID- 27189497 TI - Connection of functional quality of partial removable dentures and the degree of patients' phonetic adaptation. AB - INTRODUCTION: Phonetic adaptation is a complex biological phenomenon with a highly individual course, depending on the patient's motivation to use prosthesis, on the functional quality of removable dentures. The aim of the study was to estimate phonetic adaptation in patients with partial dentures, connecting it to alteration in speech quality and dentures functional value. MATERIALS AND METHODS: We examined some peculiarities of phonetic adaptation in 50 patients with removable dentures (50 patients with natural dentition were invited for the control group). The standardized evaluation protocols (12 speech quality determining parameters) were developed separately for Latvian and Russian native speakers. 500 speech video samples were recorded and analysed according to pre established guidelines. The connection of speech quality and the functional quality of the dentures was assessed. Statistical analysis was performed using SPSS 20.0. P values equal to or less than 0.05 were considered to be statistically significant. RESULTS: In patients with appropriate functional quality of removable dentures distorted speech production was detected in 25% (pk=0.008) cases and in patients with inappropriate functional quality of the prosthesis - in 40% (pk<0.001). Patients with appropriate dentures functional value were satisfied with their speech performance in 96% (pk=0.674), in the group with inappropriate dentures functional value only 59% (p<0.001) rated their speech quality positively. CONCLUSION: Phonetic adaptation to removable dentures depends on the patient's individual adaptation capacity, prosthetic design and functional value. Thus statistically significant correlation between removable partial dentures functional value, duration of usage and the degree of patients' phonetic adaptation (p<0.001) may be considered to be confirmed. PMID- 27189498 TI - Upper airway obstuction in class II patients. Effects of Andresen activator on the anatomy of pharingeal airway passage. Cone beam evalution. AB - AIM: The aim of this study is to assess the response and changes on pharyngeal airway passage (PAP) to class II Andresen appliance in class II growing patients with obstructive sleep apnea syndrome (OSAS). METHODS: The sample consisted of forty patients with a class II malocclusion in the age range of 9 to 14 years with mandibular retrusion and OSAS and ten control group subjects. A CBCT was taken before treatment (T0) and a second one after a follow-up period of approximately 16 months (T1). The dimensions of PAP were determined according to the method described by Jena et al. with Mimics program. The following parameters were considered: DOP, DPH, MP-H, PAS, PNS-U, SNA, SNB, ANB. The statistical analysis was carried out with t test. RESULTS: The change in ANB, SNB, MP-H, PNS U, PAS was significantly more in the patients undergoing treatment as compared to the control group. The improvement of DOP and DPH among the treatment group subjects was significantly more compared to the control group subjects. CONCLUSIONS: Class II correction by functional appliances during childhood might help to eliminate the adaptive changes in the upper airway and predisposing factors to OSAS, thus decreasing the risk of OSAS development in adulthood. PMID- 27189499 TI - A rare variant of calcifying odontogenic cyst with ameloblastoma presentation. AB - Calcifying odontogenic cyst is a rare entity which was first described by Gorlin, and also accounts for 1% of the jaw cysts according to Shear. Due to its diverse histopathology and variable clinical features, there has been a doubt regarding its nature as a cyst or a neoplasm. In this report we present a case of calcifying odontogenic cyst with mural ameloblastomatous presentation in the left body of the mandible in a 19-year-old male patient. This is the 15th case of ameloblastomatous COC being documented in literature. PMID- 27189500 TI - An unusual complication of genioglossus advancement surgery. AB - OBJECTIVE: Genioglossus advancement is a surgical procedure where the base of the tongue is pulled forward, usually to increase airway size due to deformity or a sleep breathing disorder. In this procedure, a small bony window is made in the lower jaw. The piece of bone along with the attachment for the tongue is pulled forward and down, then fastened to the outside of the lower jaw. Here we report a 43 year old male patient which has admitted to our department with the complaints of the mild pain and swelling on the chin area. MATERIAL AND METHODS: The patient underwent a genioglossus advancement surgery 3 months ago. An ortopantomograph revealed a root fracture of the lower left canine. Under mandibular nerve block, the lower left canine was extracted and the root piece was removed via an endodontic K-file. RESULTS: The healing period was uneventfull and no signs or symptoms of a pathology was detected. CONCLUSION: Dental complications related to genioglossus advancement are rarely reported. However, the surgeons should be aware of damage the roots of the adjacent teeth, especially the lower canines. PMID- 27189501 TI - Videoconferencing and telementoring about dementia care: evaluation of a pilot model for sharing scarce old age psychiatry resources. AB - BACKGROUND: While videoconferencing, telementoring, and peer support have been shown to enhance services in some instances, there has been no research investigating the use of these technologies in supporting professionals managing clients with dementia. The objective of this research was to evaluate expansion of an old age psychiatry consultation service and pilot test a model to improve medical supervision and clinical governance for staff within regional and remote areas using remote information technology. METHODS: The design was a mixed methods (qualitative and quantitative) evaluation using before, mid-point and post-implementation semi-structured interviews and questionnaires to examine orientation, acceptance, and impact underpinned by theoretical approaches to evaluation. Education evaluations used a Likert style response template. Participants were 18 dementia service staff, including staff from linked services and old age psychiatrists. Qualitative interviews addressed the pilot implementation including: expectations, experiences, strategies for improving the pilot, and perceived impact on work practice and professional development opportunities. RESULTS: There was high satisfaction with the program. The case conference process contributed to perceived improved outcomes for clients, family, and staff. Clinicians perceived improvement in family carer and staff carer stress and their confidence in managing clients with behavioral and psychological symptoms of dementia (BPSD). Thematic analysis indicated that the pilot enhanced professional development, decreased travel time, and improved team cohesion. CONCLUSIONS: Given the increasing aging population in regional, rural, and remote areas, initiatives using videoconferencing and telementoring will help to develop a confident and skilled workforce. This pilot program was found to be acceptable and feasible. Potential benefits for clients and family carers should be examined in future resesarch. PMID- 27189503 TI - Cloning and expression of long neuropeptide F and the role of FMRFamide-like peptides in regulating egg production in the Chagas vector, Rhodnius prolixus. AB - Long neuropeptide F (NPF) is a neuropeptide implicated in the control of feeding, digestion and reproduction in various insect species. Here we have isolated the cDNA sequence encoding NPF in Rhodnius prolixus (RhoprNPF). The RhoprNPF gene is composed of 3 exons and 2 introns, one of which is present in the peptide coding region. RhoprNPF is 42 amino acids long and has the characteristic RFamide C terminus, which is common of FMRFamide-like peptides (FLPs). Quantitative PCR (qPCR) shows that RhoprNPF mRNA is present in higher amounts in fifth instars than in adults, implying that it may play a role in growth and development. In situ hybridization shows that the RhoprNPF transcript is present in median neurosecretory cells (MNSCs) in the brain, cells in the fifth instar hindgut and cells along the longitudinal muscle fibers of the adult female lateral oviducts. Injection of the last 8 amino acids of RhoprNPF (truncated RhoprNPF, AVAGRPRFa), which is considered to be the active core sequence for biological activity, into mated, fed, female adult R. prolixus decreased the number of eggs found in the ovaries as well as increased the number of eggs laid. This suggests that RhoprNPF may play a role in accelerating the process of ovulation from the ovary of the female R. prolixus. An increase in oogenesis was observed following the injection of other FLPs such as RhoprShortNPF, GNDNFMRFamide and AKDNFIRFamide, whereas the FLP, RhoprMS, and the allatostatin, RhoprAST-2, inhibited egg production. PMID- 27189502 TI - The influence of deficient retro-aortic rim on technical success and early adverse events following device closure of secundum atrial septal defects: An Analysis of the IMPACT Registry(r). AB - BACKGROUND: Concern regarding aortic erosion has focused attention on the retro aortic rim in patients undergoing device closure of atrial septal defects (ASD), but its effect on early outcomes is not well studied. METHODS: A multicenter retrospective cohort study of patients undergoing device occlusion of ASD between 1/2011-10/2014 was performed, using data from the IMproving Pediatric and Adult Congenital Treatment Registry. Subjects were divided between those with retro aortic rim <5 and >=5 mm. Primary outcomes were technical failure and major early adverse events. Case times were measured as surrogates of technical complexity. The effect of deficient retro-aortic rim on primary outcomes was assessed using hierarchical logistic regression, adjusting for other suspected covariates and assessing whether they represent independent risk factors RESULTS: 1,564 subjects (from 77 centers) were included, with deficient retro-aortic rim present in 40%. Technical failure occurred in 91 subjects (5.8%) and a major early adverse event in 64 subjects (4.1%). Adjusting for known covariates, the presence of a deficient retro-aortic rim was not significantly associated with technical failure (OR: 1.3, 95% CI: 0.9-2.1) or major early adverse event (OR: 0.7, 95% CI: 0.4-1. 2). Total case (P = 0.01) and fluoroscopy time (P = 0.02) were greater in subjects with deficient rim, but sheath time was not significantly different (P = 0.07). Additional covariates independently associated with these outcomes were identified. CONCLUSION: Deficient retro-aortic rim was highly prevalent but not associated with increased risk of technical failure or early adverse events. Studies with longer follow-up are necessary to assess other outcomes, including device erosion. (c) 2016 Wiley Periodicals, Inc. PMID- 27189504 TI - Universal quantum correlation close to quantum critical phenomena. AB - We study the ground state quantum correlation of Ising model in a transverse field (ITF) by implementing the quantum renormalization group (QRG) theory. It is shown that various quantum correlation measures and the Clauser-Horne-Shimony Holt inequality will highlight the critical point related with quantum phase transitions, and demonstrate nonanalytic phenomena and scaling behavior when the size of the systems becomes large. Our results also indicate a universal behavior of the critical exponent of ITF under QRG theory that the critical exponent of different measures is identical, even when the quantities vary from entanglement measures to quantum correlation measures. This means that the two kinds of quantum correlation criterion including the entanglement-separability paradigm and the information-theoretic paradigm have some connections between them. These remarkable behaviors may have important implications on condensed matter physics because the critical exponent directly associates with the correlation length exponent. PMID- 27189505 TI - In situ optical measurement of the rapid Li intercalation and deintercalation dynamics in colloidal 2D layered TiS2 nanodiscs. AB - We report the in situ optical measurements of the rapid Li intercalation and deintercalation dynamics in 2-dimensional (2D) layered transition metal dichalcogenide (TMD) with a nanoscale lateral dimension using thin films fabricated with size-controlled colloidal TiS2 nanodiscs. The films exhibiting high optical homogeneity, where the interband absorption changes near-linearly to the amount of intercalated Li, enabled facile optical probing of the intercalation dynamics overcoming the shortcomings of amperometry susceptible to complications from non-Faradaic processes. The time scale of Li intercalation and deintercalation was on the order of seconds in the nanodiscs of ~100 nm lateral dimension, indicating sufficiently rapid dynamic control of the intercalation induced material properties with a reduced lateral dimension. The change in the rate and reversibility of the dynamics during the multiple intercalation/deintercalation cycles was also measured, providing a unique window to observe the effect of potential structural changes on the intercalation and deintercalation dynamics in 2D layered TMD structures with a nanoscale lateral dimension. PMID- 27189507 TI - A competitive luminol chemiluminescence immunosensor based on a microfluidic chip for the determination of ractopamine. AB - Herein, a competitive luminol chemiluminescence immunosensor based on a microfluidic chip was developed to detect ractopamine (RCT) both in phosphate buffer and swine urine samples. The immunosensor can provide a liner range of 0.5 40 ng/mL and a high sensitivity with a limit of detection of 0.97 ng/mL for RCT detection in swine urine. Good rates of recovery in negative swine urine samples were achieved over the RCT concentration ranging from 0.5 to 40 ng/mL. The proposed method offered a promising analytical scheme for the on-site determination of RCT. PMID- 27189508 TI - Changes in bird-migration patterns associated with human-induced mortality. AB - Many bird populations have recently changed their migratory behavior in response to alterations of the environment. We collected data over 16 years on male Great Bustards (Otis tarda), a species showing a partial migratory pattern (sedentary and migratory birds coexisting in the same breeding groups). We conducted population counts and radio tracked 180 individuals to examine differences in survival rates between migratory and sedentary individuals and evaluate possible effects of these differences on the migratory pattern of the population. Overall, 65% of individuals migrated and 35% did not. The average distance between breeding and postbreeding areas of migrant individuals was 89.9 km, and the longest average movement of sedentary males was 3.8 km. Breeding group and migration distance had no effect on survival. However, mortality of migrants was 2.4 to 3.5 times higher than mortality of sedentary birds. For marked males, collision with power lines was the main cause of death from unnatural causes (37.6% of all deaths), and migratory birds died in collisions with power lines more frequently than sedentary birds (21.3% vs 6.3%). The percentage of sedentary individuals increased from 17% in 1997 to 45% in 2012. These results were consistent with data collected from radio-tracked individuals: The proportion of migratory individuals decreased from 86% in 1997-1999 to 44% in 2006-2010. The observed decrease in the migratory tendency was not related to climatic changes (temperatures did not change over the study period) or improvements in habitat quality (dry cereal farmland area decreased in the main study area). Our findings suggest that human-induced mortality during migration may be an important factor shaping the migration patterns of species inhabiting humanized landscapes. PMID- 27189509 TI - Subjective evaluation of a peer support program by women with breast cancer: A qualitative study. AB - AIM: The aim of this study was to determine the subjective evaluation of a breast cancer peer support program based on a survey of the participants who completed the program. METHODS: Semistructured interviews were held with 10 women with breast cancer. The responses were subject to a qualitative inductive analysis. RESULTS: Women with breast cancer who participated in the breast cancer peer support program evaluated the features of the program and cited benefits, such as "Receiving individual peer support tailored to your needs," "Easily consulted trained peer supporters," and "Excellent coordination." Also indicated were benefits of the peer support that was received, such as "Receiving peer-specific emotional support," "Obtaining specific experimental information," "Re-examining yourself," and "Making preparations to move forward." The women also spoke of disadvantages, such as "Strict management of personal information" and "Matching limitations." CONCLUSIONS: In this study, the subjective evaluation of a peer support program by women with breast cancer was clarified . The women with breast cancer felt that the program had many benefits and some disadvantages. These results suggest that there is potential for peer support-based patient-support programs in medical services that are complementary to the current support that is provided by professionals. PMID- 27189510 TI - Comparison of open reduction versus minimally invasive surgical approaches on screw position in canine sacroiliac lag-screw fixation. AB - OBJECTIVE: To compare accuracy and consistency of sacral screw placement in canine pelves treated for sacroiliac luxation with open reduction and internal fixation (ORIF) or minimally invasive osteosynthesis (MIO) techniques. METHODS: Unilateral sacroiliac luxations created experimentally in canine cadavers were stabilized with an iliosacral lag screw applied via ORIF or MIO techniques (n = 10/group). Dorsoventral and craniocaudal screw angles were measured using computed tomography multiplanar reconstructions in transverse and dorsal planes, respectively. Ratios between pilot hole length and sacral width (PL/SW-R) were obtained. Data between groups were compared statistically (p <0.05). RESULTS: Mean screw angles (+/-SD) were greater in ORIF specimens in both transverse (p <0.001) and dorsal planes (p <0.004). Mean PL/SW-R was smaller (p <0.001) in the ORIF group, yet was greater than 60%. While pilot holes exited the first sacral end-plate in three of 10 ORIF specimens, the spinal canal was not violated in either group. CONCLUSIONS: This study demonstrates that MIO fixation of canine sacroiliac luxations provides more accurate and consistent sacral screw placement than ORIF. With proper techniques, iatrogenic neurological damage can be avoided with both techniques. The PL /SW-R, which relates to safe screw fixation, also demonstrates that screw penetration of at least 60% of the sacral width is achievable regardless of surgical approach. These findings, along with the limited dissection needed for accurate sacral screw placement, suggest that MIO of sacroiliac luxations is a valid alternative to ORIF. PMID- 27189512 TI - Photoinduced DNA Interstrand Cross-Link Formation by Naphthalene Boronates via a Carbocation. AB - Most photoinduced DNA cross-link formation by a bifunctional aryl derivative is through a bisquinone methide. DNA cross-linking via a bisarylcarbocation remains a less explored area. We designed and synthesized a series of naphthalene boronates that produce DNA interstrand cross-links via a carbocation upon UV irradiation. A free radical was generated from the naphthalene boronates with 350 nm irradiation and further converted to a carbocation by electron transfer. The activation mechanism was determined using the orthogonal traps, 2,2,6,6 tetramethylpiperidin-1-oxyl (TEMPO) and methoxyamine that react with either the free radical or the carbocation but not both. This represents a novel example of photoinduced DNA cross-link formation via carbocations generated from a bisaryl derivative. This work provides information useful for the design of novel photoactivated DNA cross-linking agents. PMID- 27189511 TI - Silence of bFGF enhances chemosensitivity of glioma cells to temozolomide through the MAPK signal pathway. AB - Basic fibroblast growth factor (bFGF) is a multifunctional growth factor in glioma cells and has been proved to be associated with the grade malignancy of glioma and prognosis of patients. Although there is evidence showing that bFGF plays an important role in proliferation, differentiation, angiogenesis, and survival of glioma cells, the effect of bFGF on chemosensitivity of glioma has not been verified. In this study, we analyzed the relationship between bFGF and chemotherapy resistance, with the objective of offering new strategy for chemotherapy of glioma patients. Here, siRNA was used to silence the expression of bFGF in glioma cell lines including U87 and U251 followed by chemotherapy of temozolomide (TMZ). Then, the characters of glioma including proliferation, apoptosis, migration, and cell cycle were studied in U87 and U251 cell lines. Our results demonstrated that silencing bFGF enhanced the effect of TMZ by inhibiting proliferation and migration, blocking cell cycle in G0/G1, and promoting apoptosis. In addition, the phosphorylation level of MAPK was measured to explore the mechanism of chemosensitization. The results showed that bFGF could promote the activation of the MAPK signal pathway. Our data indicated that bFGF might be a potential target for chemotherapy through the MAPK signal pathway. PMID- 27189513 TI - Increased consultation frequency in primary care, a risk marker for cancer: a case-control study. AB - OBJECTIVE: To identify early diagnostic profiles such as diagnostic codes and consultation patterns of cancer patients in primary care one year prior to cancer diagnosis. DESIGN: Total population-based case-control study. SETTING AND SUBJECTS: 4562 cancer patients and 17,979 controls matched by age, sex, and primary care unit. Data were collected from the Swedish Cancer Register and the Regional Healthcare Database. METHOD: We identified cancer patients in the Vastra Gotaland Region of Sweden diagnosed in 2011 with prostate, breast, colorectal, lung, gynaecological, and skin cancers including malignant melanoma. We studied the symptoms and diagnoses identified by diagnostic codes during a diagnostic interval of 12 months before the cancer diagnosis. MAIN OUTCOME MEASURES: Consultation frequency, symptom density by cancer type, prevalence and odds ratios (OR) for the diagnostic codes in the cancer population as a whole. RESULTS: The diagnostic codes with the highest OR were unspecified lump in breast, neoplasm of uncertain behaviour, and abnormal serum enzyme levels. The codes with the highest prevalence were hyperplasia of prostate, other skin changes and abdominal and pelvic pain. The frequency of diagnostic codes and consultations in primary care rose in tandem 50 days before diagnosis for breast and gynaecological cancer, 60 days for malignant melanoma and skin cancer, 80 days for prostate cancer and 100 days for colorectal and lung cancer. CONCLUSION: Eighty-seven percent of patients with the most common cancers consulted a general practitioner (GP) a year before their diagnosis. An increase in consultation frequency and presentation of any symptom should raise the GP's suspicion of cancer. Key points Knowledge about the prevalence of early symptoms and other clinical signs in cancer patients in primary care remains insufficient. * Eighty seven percent of the patients with the seven most common cancers consulted a general practitioner 12 months prior to cancer diagnosis. * Both the frequency of consultation and the number of symptoms and diseases expressed in diagnostic codes rose in tandem 50-100 days before the cancer diagnosis. * Unless it is caused by a previously known disease, an increased consultation rate for any symptom should result in a swift investigation or referral from primary care to confirm or exclude cancer. PMID- 27189514 TI - Repression of callus initiation by the miRNA-directed interaction of auxin cytokinin in Arabidopsis thaliana. AB - In tissue culture systems plant cells can be induced to regenerate to whole plants. A particularly striking example of cellular reprogramming is seen in this regeneration process, which typically begins with the induction of an intermediate cell mass referred to as callus. The identity of the key genetic cues associated with callus formation is still largely unknown. Here a microRNA directed phytohormonal interaction is described which represses callus initiation and formation in Arabidopsis thaliana. miR160 and ARF10 (At2g28350), a gene encoding an auxin response factor, were shown to exhibit a contrasting pattern of transcription during callus initiation from pericycle-like cells. The callus initiation is faster and more prolific in a miR160-resistant form of ARF10 (mARF10), but slower and less prolific in the transgenic line over-expressing miR160c (At5g46845), arf10 and arf10 arf16 mutants than that in the wild type. ARF10 repressed the expression of Arabidopsis Response Regulator15 (ARR15, At1g74890) via its direct binding to the gene's promoter. The loss of function of ARR15 enhanced callus initiation and partly rescued the phenotype induced by the transgene Pro35S:miR160c. Overexpression of ARR15 partly rescues the callus initiation defect of mARF10 plants. Our findings define miR160 as a key repressor of callus formation and reveal that the initiation of callus is repressed by miR160-directed interaction between auxin and cytokinin. PMID- 27189515 TI - The factors influencing burnout and job satisfaction among critical care nurses: a study of Saudi critical care nurses. AB - AIM: The aim of the study was to explore the prevalence of burnout and job satisfaction among Saudi national critical care nurses. BACKGROUND: Burnout is caused by a number of factors, including personal, organisational and professional issues. Previous literature reports a strong relationship between burnout and job satisfaction among critical care nurses. Little is known about this phenomenon among Saudi national critical care nurses. METHODS: A convenience sample of 150 Saudi national critical care nurses from three hospitals in Hail, Saudi Arabia were included in a cross-sectional survey. RESULTS: Saudi national critical care registered nurses reported moderate to high levels of burnout in the areas of emotional exhaustion and depersonalisation. Participants also reported a feeling of ambivalence and dissatisfaction with their jobs but were satisfied with the nature of their work. CONCLUSIONS: Saudi national critical care nurses experience moderate to high levels of burnout and low levels of job satisfaction. Burnout is a predictor of job satisfaction for Saudi national critical care nurses. IMPLICATIONS FOR NURSING AND HEALTH POLICY: These results provide clear evidence of the need for nurse managers and policy makers to devise strategies to help nurses better cope with a stressful work environment, thereby also improving job satisfaction among Saudi national critical care nurses. PMID- 27189517 TI - Influence of affective auditory stimuli on balance control during static stance. AB - The main purpose of this study was to examine the effects of affective auditory stimuli on balance control during static stance. Twelve female and 12 male participants were recruited. Each participant completed four upright standing trials including three auditory stimuli trials and one baseline trial (ie no auditory stimuli). The three auditory stimuli trials corresponded to the pleasant, neutral and unpleasant sound conditions. Center of pressure (COP) measures were used to quantify balance control performance. It was found that unpleasant auditory stimuli were associated with larger COP amplitude in the AP direction compared to the rest testing conditions. There were no significant interaction effects between 'auditory stimuli' and gender. These findings suggested that some specificities presented by auditory stimuli are important for balance control, and the effects of auditory stimuli on balance control were dependent on their affective components. Practitioner Summary: Findings from this study can aid in better understanding of the relationship between auditory stimuli and balance control. In particular, unpleasant auditory stimuli were found to result in poorer balance control and higher fall risks. Therefore, to prevent fall accidents, interventions should be developed to reduce exposures to unpleasant sound. PMID- 27189516 TI - Rho kinase inhibitor enables cell-based therapy for corneal endothelial dysfunction. AB - The corneal endothelium maintains corneal transparency; consequently, its dysfunction causes severe vision loss. Tissue engineering-based therapy, as an alternative to conventional donor corneal transplantation, is anticipated to provide a less invasive and more effective therapeutic modality. We conducted a preclinical study for cell-based therapy in a primate model and demonstrated regeneration of the corneal endothelium following injection of cultured monkey corneal endothelial cells (MCECs) or human CECs (HCECs), in combination with a Rho kinase (ROCK) inhibitor, Y-27632, into the anterior chamber. We also evaluated the safety and efficacy of Good Manufacturing Practice (GMP)-grade HCECs, similar to those planned for use as transplant material for human patients in a clinical trial, and we showed that the corneal endothelium was regenerated without adverse effect. We also showed that CEC engraftment is impaired by limited substrate adhesion, which is due to actomyosin contraction induced by dissociation-induced activation of ROCK/MLC signaling. Inclusion of a ROCK inhibitor improves efficiency of engraftment of CECs and enables cell-based therapy for treating corneal endothelial dysfunction as a clinically relevant therapy. PMID- 27189518 TI - Two new species of Rhabdias Stiles et Hassall, 1905 (Nematoda: Rhabdiasidae) from anuran amphibians in Para, Brazil. AB - Two new lung-dwelling nematode species of the genus Rhabdias Stiles et Hassall, 1905 were discovered in Caxiuana National Forest, Para state, Brazil. Rhabdias galactonoti sp. n. was found in a dendrobatid frog Adelphobates galactonotus (Steindachner). The species is characterised by the regularly folded inner surface of the anterior part of the buccal capsule seen in apical view, flask shaped oesophageal bulb and narrow, elongated tail. Rhabdias stenocephala sp. n. from two species of leptodactylid frogs, Leptodactylus pentadactylus (Laurenti) (type host) and L. paraensis (Heyer), is characterised by a narrow anterior end that is separated from the remaining body by a constriction. Both species possess six small but distinct lips, a cuticle that is inflated along the whole body, a doliiform buccal capsule separated into a longer anterior and a shallow, ring shaped posterior part, lateral pores in the body cuticle and zones of spermatogenesis in the syngonia. Rhabdias galactonoti sp. n. is the first species of the genus found in Dendrobatidae; R. stenocephala sp. n. is the second species described from Leptodactylidae in eastern Amazonia. PMID- 27189520 TI - The patient-physician interaction as a meeting of experts: one solution to the problem of patient non-adherence. AB - Patient non-adherence is a common and important concern in clinical medicine. Some cases of patient non-adherence are cases in which the patient disagrees with the physician's recommended treatment based on particular reasons. Drawing upon science and technology studies literature, specifically the discussion by Collins and Evans and Wynne of how best to understand scientific controversies, I relate their ideas to the analogous conflict that may occur within a clinical interaction. I draw upon their recognition of the importance of contributory expertise and interactional expertise in providing legitimate knowledge. I also draw upon Wynne's idea of the 'negotiation of meanings' as an important element of the clinical interaction. To resolve potential conflicts between patient and physician before they develop into 'non-adherence', I propose the implementation of a new epistemological framework that recognizes legitimate knowledge offered by the patient as well as the physician. By situating this patient expertise framework within the paradigm of patient-centred medicine, and by assuming the goal of medical treatment to be treatment of suffering, patient expertise becomes centralized as a means of determining the nature of patient suffering. Two aspects of the patient's tacit knowledge - the body aspect and the meaning aspect - both of which are context-dependent and directly accessible only to the patient, are thus recognized as knowledge essential to the success of the interaction. The physician's role becomes that of both medical expert and possessor of 'interactional expertise', by which the physician recognizes and includes patient expertise in the treatment decision. By recognizing and incorporating the negotiation of meanings into the development of a treatment plan, this epistemological model of patient expertise should prevent cases of non adherence based on disagreement. PMID- 27189519 TI - Evolutionary origin of the NCSI gene subfamily encoding norcoclaurine synthase is associated with the biosynthesis of benzylisoquinoline alkaloids in plants. AB - Sacred lotus is rich in biologically active compounds, particularly benzylisoquinoline alkaloids (BIAs). Here, we report on isolation of genes encoding (S)-norcoclaurine synthase (NCS) in sacred lotus, which is a key entry enzyme in BIA biosynthesis. Seven NCS genes, designated NnNCS1 through NnNCS7, were identified in the sacred lotus genome, and five are located next to each other within a 83 kb region on scaffold 8. The NCS genes are divided into two subfamilies, designated NCSI and NCSII. The NCSII genes are universal in plants, while the NCSI genes are only identified in a limited number of dicotyledonous taxa that produce BIAs. In sacred lotus, only NnNCS4 belongs to the NCSII subfamily, whilst the rest NCS genes within the NCSI subfamily. Overall, the NnNCS7 gene was predominantly expressed in all tested tissues, and its expression is significantly correlated with alkaloid content in leaf. In contrast, the NnNCS4 expression shows no significant correlation with alkaloid accumulation in leaf, and its lack of expression cannot inhibit alkaloid accumulation. Taken together, these results suggest that the NCSI subfamily is crucial for BIA biosynthesis, and its origin may represent an important evolutionary event that allows certain plant taxa to produce BIAs. PMID- 27189521 TI - What are the mechanisms of regeneration inhibition in alcoholic hepatitis? PMID- 27189523 TI - Impact of heart and lung dose on early survival in patients with non-small cell lung cancer treated with chemoradiation. AB - BACKGROUND AND PURPOSE: To determine whether the impact of heart dose on early overall survival (OS) reported in RTOG 0617 could be confirmed in an independent cohort. MATERIALS AND METHODS: Heart and lung dose-volume histogram data were retrospectively extracted for patients with stage IIIA-IIIB non-small cell lung cancer (NSCLC) who had received radiotherapy using 3D CRT, IMRT or proton therapy delivered with concurrent chemotherapy between 1999 and 2010. Potential associations between clinical and dosimetric factors and OS up to 24months after start of treatment were assessed in univariate and multivariate analyses with log rank tests or Cox proportional hazards models. RESULTS: 468 patients met inclusion criteria. Factors associated with increased risk of early death in univariate analyses were performance status (PS), stage, treatment with 3D conformal radiotherapy, lower tumor dose and larger gross tumor volume (GTV), mean heart dose (MHD), heart V5, mean lung dose (MLD) and lung V5. Factors retaining significance in multivariate analysis were PS, GTV, and MLD. There was a strong correlation between MHD and heart V5 with MLD. However, no evidence was found that heart doses had an independent effect on OS during the first 2years. CONCLUSIONS: In a large group of patients treated with chemoradiation for locally advanced NSCLC, heart dose was not found to be associated with early survival outcomes when lung dose was taken into account. Nevertheless, based on the known adverse effects of radiotherapy on vasculature and cardiac function, dose to the heart should be minimized during radiotherapy planning. PMID- 27189522 TI - Mitigation of nitrogen mustard mediated skin injury by a novel indomethacin bifunctional prodrug. AB - Nitrogen mustard (NM) is a bifunctional alkylating agent that is highly reactive in the skin causing extensive tissue damage and blistering. In the present studies, a modified cutaneous murine patch model was developed to characterize NM induced injury and to evaluate the efficacy of an indomethacin pro-drug in mitigating toxicity. NM (20MUmol) or vehicle control was applied onto 6mm glass microfiber filters affixed to the shaved dorsal skin of CD-1 mice for 6min. This resulted in absorption of approximately 4MUmol of NM. NM caused localized skin damage within 1 d, progressing to an eschar within 2-3 d, followed by wound healing after 4-5 d. NM-induced injury was associated with increases in skin thickness, inflammatory cell infiltration, reduced numbers of sebocytes, basal keratinocyte double stranded DNA breaks, as measured by phospho-histone 2A.X expression, mast cell degranulation and increases in inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Wound healing was characterized by epidermal hyperplasia and marked increases in basal cells expressing proliferating cell nuclear antigen. A novel indomethacin-anticholinergic prodrug (4338) designed to target cyclooxygenases and acetylcholinesterase (AChE), was found to markedly suppress NM toxicity, decreasing wound thickness and eschar formation. The prodrug also inhibited mast cell degranulation, suppressed keratinocyte expression of iNOS and COX-2, as well as markers of epidermal proliferation. These findings indicate that a novel bifunctional pro-drug is effective in limiting NM mediated dermal injury. Moreover, our newly developed cutaneous patch model is a sensitive and reproducible method to assess the mechanism of action of countermeasures. PMID- 27189524 TI - Schizophrenia. AB - Schizophrenia is a chronic psychiatric disorder with a heterogeneous genetic and neurobiological background that influences early brain development, and is expressed as a combination of psychotic symptoms - such as hallucinations, delusions and disorganization - and motivational and cognitive dysfunctions. The mean lifetime prevalence of the disorder is just below 1%, but large regional differences in prevalence rates are evident owing to disparities in urbanicity and patterns of immigration. Although gross brain pathology is not a characteristic of schizophrenia, the disorder involves subtle pathological changes in specific neural cell populations and in cell-cell communication. Schizophrenia, as a cognitive and behavioural disorder, is ultimately about how the brain processes information. Indeed, neuroimaging studies have shown that information processing is functionally abnormal in patients with first-episode and chronic schizophrenia. Although pharmacological treatments for schizophrenia can relieve psychotic symptoms, such drugs generally do not lead to substantial improvements in social, cognitive and occupational functioning. Psychosocial interventions such as cognitive-behavioural therapy, cognitive remediation and supported education and employment have added treatment value, but are inconsistently applied. Given that schizophrenia starts many years before a diagnosis is typically made, the identification of individuals at risk and those in the early phases of the disorder, and the exploration of preventive approaches are crucial. PMID- 27189526 TI - Adenosine Triphosphate stimulates differentiation and mineralization in human osteoblast-like Saos-2 cells. AB - In the last years adenosine triphosphate (ATP) and subsequent purinergic system activation through P2 receptors were investigated highlighting their pivotal role in bone tissue biology. In osteoblasts ATP can regulate several activities like cell proliferation, cell death, cell differentiation and matrix mineralization. Since controversial results exist, in this study we analyzed the ATP effects on differentiation and mineralization in human osteoblast-like Saos-2 cells. We showed for the first time the altered functional activity of ATP receptors. Despite that, we found that ATP can reduce cell proliferation and stimulate osteogenic differentiation mainly in the early stages of in vitro maturation as evidenced by the enhanced expression of alkaline phosphatase (ALP), Runt-related transcription factor 2 (Runx2) and Osteocalcin (OC) genes and by the increased ALP activity. Moreover, we found that ATP can affect mineralization in a biphasic manner, at low concentrations ATP always increases mineral deposition while at high concentrations it always reduces mineral deposition. In conclusion, we show the osteogenic effect of ATP on both early and late stage activities like differentiation and mineralization, for the first time in human osteoblastic cells. PMID- 27189527 TI - Fibromyalgia. AB - Fibromyalgia is a common illness characterized by chronic widespread pain, sleep problems (including unrefreshing sleep), physical exhaustion and cognitive difficulties. The definition, pathogenesis and treatment are controversial, and some even contest the existence of this disorder. In 1990, the American College of Rheumatology (ACR) defined classification criteria that required multiple tender points (areas of tenderness occurring in muscles and muscle-tendon junctions) and chronic widespread pain. In 2010, the ACR preliminary diagnostic criteria excluded tender points, allowed less extensive pain and placed reliance on patient-reported somatic symptoms and cognitive difficulties. Fibromyalgia occurs in all populations worldwide, and symptom prevalence ranges between 2% and 4% in the general population. The prevalence of people who are actually diagnosed with fibromyalgia ('administrative prevalence') is much lower. A model of fibromyalgia pathogenesis has been suggested in which biological and psychosocial variables interact to influence the predisposition, triggering and aggravation of a chronic disease, but the details are unclear. Diagnosis requires the history of a typical cluster of symptoms and the exclusion of a somatic disease that sufficiently explains the symptoms by medical examination. Current evidence-based guidelines emphasize the value of multimodal treatments, which encompass both non pharmacological and selected pharmacological treatments tailored to individual symptoms, including pain, fatigue, sleep problems and mood problems. For an illustrated summary of this Primer, visit: http://go.nature.com/LIBdDX. PMID- 27189525 TI - Globally prevalent PfMDR1 mutations modulate Plasmodium falciparum susceptibility to artemisinin-based combination therapies. AB - Antimalarial chemotherapy, globally reliant on artemisinin-based combination therapies (ACTs), is threatened by the spread of drug resistance in Plasmodium falciparum parasites. Here we use zinc-finger nucleases to genetically modify the multidrug resistance-1 transporter PfMDR1 at amino acids 86 and 184, and demonstrate that the widely prevalent N86Y mutation augments resistance to the ACT partner drug amodiaquine and the former first-line agent chloroquine. In contrast, N86Y increases parasite susceptibility to the partner drugs lumefantrine and mefloquine, and the active artemisinin metabolite dihydroartemisinin. The PfMDR1 N86 plus Y184F isoform moderately reduces piperaquine potency in strains expressing an Asian/African variant of the chloroquine resistance transporter PfCRT. Mutations in both digestive vacuole resident transporters are thought to differentially regulate ACT drug interactions with host haem, a product of parasite-mediated haemoglobin degradation. Global mapping of these mutations illustrates where the different ACTs could be selectively deployed to optimize treatment based on regional differences in PfMDR1 haplotypes. PMID- 27189528 TI - Methylprednisolone acetate-loaded hydroxyapatite nanoparticles as a potential drug delivery system for treatment of rheumatoid arthritis: In vitro and in vivo evaluations. AB - The objective of this study was to improve the therapeutic efficacy of methylprednisolone acetate (MPA) in the treatment of rheumatoid arthritis (RA) by incorporating the drug into the hydroxyapatite (HAp) nanoparticles. The nanoparticles were synthesized using a chemical precipitation technique and their size and morphology were evaluated by dynamic light scattering and scanning electron microscopy (SEM). The solid-state behavior of the nanoparticles was also characterized by operating X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR). The Brunauer-Emmett-Teller and Barrett-Joyner-Halenda N2 adsorption/desorption analyses were also performed to determine the surface area, Vm (the volume of the N2 adsorbed on the one gram of the HAp when the monolayer is complete) and the pore size of the samples. Furthermore, the therapeutic efficacy of the prepared nanoformulation on the adjuvant induced arthritic rats was assessed. HAp mesoporous nanoparticles with a particle size of 70.45nm, pore size of 2.71nm and drug loading of 44.53% were obtained. The specific surface area of HAp as well as the Vm values were decreased after the drug loading process. The nanoformulation revealed the slower drug release profile compared to the pure drug. The MTT assay indicated that the MPA-loaded nanoparticles had a lower cytotoxic effect on NIH 3T3 and CAOV-4 cell lines compared to the pure drug. Interestingly, the in vivo study confirmed that the drug-loaded nanoparticles could considerably decrease the paw volume and normalize the hematological abnormalities in the arthritic rats. PMID- 27189530 TI - Anaphylaxis case report to trimethylphloroglucinol (Spasfon(r)). PMID- 27189529 TI - Spatial distribution of psychotic disorders in an urban area of France: an ecological study. AB - Previous analyses of neighbourhood variations of non-affective psychotic disorders (NAPD) have focused mainly on incidence. However, prevalence studies provide important insights on factors associated with disease evolution as well as for healthcare resource allocation. This study aimed to investigate the distribution of prevalent NAPD cases in an urban area in France. The number of cases in each neighbourhood was modelled as a function of potential confounders and ecological variables, namely: migrant density, economic deprivation and social fragmentation. This was modelled using statistical models of increasing complexity: frequentist models (using Poisson and negative binomial regressions), and several Bayesian models. For each model, assumptions validity were checked and compared as to how this fitted to the data, in order to test for possible spatial variation in prevalence. Data showed significant overdispersion (invalidating the Poisson regression model) and residual autocorrelation (suggesting the need to use Bayesian models). The best Bayesian model was Leroux's model (i.e. a model with both strong correlation between neighbouring areas and weaker correlation between areas further apart), with economic deprivation as an explanatory variable (OR = 1.13, 95% CI [1.02-1.25]). In comparison with frequentist methods, the Bayesian model showed a better fit. The number of cases showed non-random spatial distribution and was linked to economic deprivation. PMID- 27189531 TI - Sustaining the future of HIV counselling to reach 90-90-90: a regional country analysis. AB - INTRODUCTION: Counselling services are recommended by the World Health Organization and have been partially adopted by national HIV guidelines. In settings with a high HIV burden, patient education and counselling is often performed by lay workers, mainly supported with international funding. There are few examples where ministries of health have been able to absorb lay counsellors into their health systems or otherwise sustain their work. We document the role of lay cadres involved in HIV testing and counselling and adherence support and discuss approaches to sustainability. METHODS: We focused on a purposive sample of eight sub-Saharan African countries where Medecins Sans Frontieres supports HIV programmes: Guinea, Lesotho, Malawi, Mozambique, South Africa, Swaziland, Zambia and Zimbabwe. We reviewed both published and grey literature, including national policies and donor proposals, and interviewed key informants, including relevant government staff, donors and non-governmental organizations. RESULTS AND DISCUSSION: Lay counsellors play a critical role in scaling up HIV services and addressing gaps in the HIV testing and treatment cascade by providing HIV testing and counselling and adherence support at both the facility and community levels. Countries have taken various steps in recognizing lay counsellors, including harmonizing training, job descriptions and support structures. However, formal integration of this cadre into national health systems is limited, as lay counsellors are usually not included in national strategies or budgeting. CONCLUSIONS: The current trend of reduced donor support for lay counsellors, combined with lack of national prioritization, threatens the sustainability of this cadre and thereby quality HIV service delivery. PMID- 27189532 TI - The impact of HIV infection on blood leukocyte responsiveness to bacterial stimulation in asymptomatic patients and patients with bloodstream infection. AB - INTRODUCTION: HIV-induced changes in cytokine responses to bacteria may influence susceptibility to bacterial infections and the consequent inflammatory response. METHODS: We examined the impact of HIV on whole blood responsiveness to bacterial stimulation in asymptomatic subjects and patients with bacterial bloodstream infection (BSI). Whole blood was stimulated ex vivo with two bacterial Toll-like receptor agonists (lipopolysaccharide and lipoteichoic acid) and two pathogens (Streptococcus pneumoniae and non-typhoidal Salmonella), which are relevant in HIV-positive patients. Production of interferon-gamma, tumour necrosis factor alpha, interleukin-1beta and interleukin-6 was used as a read-out. RESULTS: In asymptomatic subjects, HIV infection was associated with reduced interferon gamma, release after stimulation and priming of the pro-inflammatory cytokine response to non-typhoidal Salmonella. In patients with BSI, we found no such priming effect, nor was there evidence for more profound sepsis-induced immunosuppression in BSI patients with HIV co-infection. CONCLUSIONS: These results suggest a complex effect of HIV on leukocyte responses to bacteria. However, in patients with sepsis, leukocyte responses were equally blunted in patients with and without HIV infection. PMID- 27189533 TI - Whole-body and splanchnic amino acid metabolism in sheep during an acute endotoxin challenge. AB - Supplemented protein or specific amino acids (AA) are proposed to help animals combat infection and inflammation. The current study investigates whole-body and splanchnic tissue metabolism in response to a lipopolysaccharide (LPS) challenge with or without a supplement of six AA (cysteine, glutamine, methionine, proline, serine and threonine). Eight sheep were surgically prepared with vascular catheters across the gut and liver. On two occasions, four sheep were infused through the jugular vein for 20 h with either saline or LPS from Escherichia coli (2 ng/kg body weight per min) in a random order, plus saline infused into the mesenteric vein; the other four sheep were treated with saline or LPS plus saline or six AA infused via the jugular vein into the mesenteric vein. Whole-body AA irreversible loss rate (ILR) and tissue protein metabolism were monitored by infusion of [ring-2H2]phenylalanine. LPS increased (P<0.001) ILR (+17 %), total plasma protein synthesis (+14 %) and lymphocyte protein synthesis (+386 %) but decreased albumin synthesis (-53 %, P=0.001), with no effect of AA infusion. Absorption of dietary AA was not reduced by LPS, except for glutamine. LPS increased the hepatic removal of leucine, lysine, glutamine and proline. Absolute hepatic extraction of supplemented AA increased, but, except for glutamine, this was less than the amount infused. This increased net appearance across the splanchnic bed restored arterial concentrations of five AA to, or above, values for the saline-infused period. Infusion of key AA does not appear to alter the acute period of endotoxaemic response, but it may have benefits for the chronic or recovery phases. PMID- 27189534 TI - Estimating the expected value of partial perfect information in health economic evaluations using integrated nested Laplace approximation. AB - The Expected Value of Perfect Partial Information (EVPPI) is a decision-theoretic measure of the 'cost' of parametric uncertainty in decision making used principally in health economic decision making. Despite this decision-theoretic grounding, the uptake of EVPPI calculations in practice has been slow. This is in part due to the prohibitive computational time required to estimate the EVPPI via Monte Carlo simulations. However, recent developments have demonstrated that the EVPPI can be estimated by non-parametric regression methods, which have significantly decreased the computation time required to approximate the EVPPI. Under certain circumstances, high-dimensional Gaussian Process (GP) regression is suggested, but this can still be prohibitively expensive. Applying fast computation methods developed in spatial statistics using Integrated Nested Laplace Approximations (INLA) and projecting from a high-dimensional into a low dimensional input space allows us to decrease the computation time for fitting these high-dimensional GP, often substantially. We demonstrate that the EVPPI calculated using our method for GP regression is in line with the standard GP regression method and that despite the apparent methodological complexity of this new method, R functions are available in the package BCEA to implement it simply and efficiently. (c) 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. PMID- 27189535 TI - Pretreatment of bamboo by ultra-high pressure explosion with a high-pressure homogenizer for enzymatic hydrolysis and ethanol fermentation. AB - Bamboo shoots, 2- and 5-year-old bamboo were treated by using a homogenizer in a constant suspended state, a process termed as ultra-high pressure explosion (UHPE). The bamboo powder was heated in 2% NaOH solution at 121 degrees C, and then 100MPa UHPE-treated through a homogenizer. The results verified that UHPE changed the suspension solution of powder into a stick fluid. The contents of lignin were decreased significantly. The bamboo shoots and 2-year-old bamboo were completely hydrolyzed to glucose within 48h by enzymes loading of 15 FPU of cellulase and 30IU of beta-glucosidase per gram glucan. Fermentation of enzymatic hydrolyzates with Saccharomyces cerevisiae resulted in about 89.7-95.1% of the theoretical ethanol yield after 24h. Therefore, NaOH+UHPE is argued to be a potential alternative technology for pretreatment of bamboo. PMID- 27189536 TI - Reprint of: Effect of fermentation parameters, elicitors and precursors on camptothecin production from the endophyte Fusarium solani. AB - Volumetric productivity of camptothecin from the suspension culture of the endophyte Fusarium solani was enhanced up to ~152 fold (from 0.19MUgl(-1)d(-1) to 28.9MUgl(-1)d(-1)) under optimized fermentation conditions including initial pH (6.0), temperature (32 degrees C) and agitation speed (80rpm) with (5% (v/v)) ethanol as medium component. Among various elicitors and precursors studied, tryptamine (0.5mM) as precursor and bovine serum albumin (BSA) (0.075mM) as an elicitor added on day 6 of the cultivation period resulted in maximum enhancement of camptothecin concentration (up to 4.5 and 3.4-fold, respectively). These leads provide immense scope for further enhancement in camptothecin productivity at bioreactor level. The cytotoxicity analysis of the crude camptothecin extract from the fungal biomass revealed its high effectiveness against colon and mammary gland cancer cell lines. PMID- 27189537 TI - Corrigendum. PMID- 27189539 TI - A New Orthology Assessment Method for Phylogenomic Data: Unrooted Phylogenetic Orthology. AB - Current sequencing technologies are making available unprecedented amounts of genetic data for a large variety of species including nonmodel organisms. Although many phylogenomic surveys spend considerable time finding orthologs from the wealth of sequence data, these results do not transcend the original study and after being processed for specific phylogenetic purposes these orthologs do not become stable orthology hypotheses. We describe a procedure to detect and document the phylogenetic distribution of orthologs allowing researchers to use this information to guide selection of loci best suited to test specific evolutionary questions. At the core of this pipeline is a new phylogenetic orthology method that is neither affected by the position of the root nor requires explicit assignment of outgroups. We discuss the properties of this new orthology assessment method and exemplify its utility for phylogenomics using a small insects dataset. In addition, we exemplify the pipeline to identify and document stable orthologs for the group of orb-weaving spiders (Araneoidea) using RNAseq data. The scripts used in this study, along with sample files and additional documentation, are available at https://github.com/ballesterus/UPhO. PMID- 27189540 TI - The Footprint of Polygenic Adaptation on Stress-Responsive Cis-Regulatory Divergence in the Arabidopsis Genus. AB - Adaptation of a complex trait often requires the accumulation of many modifications to finely tune its underpinning molecular components to novel environmental requirements. The investigation of cis-acting regulatory modifications can be used to pinpoint molecular systems partaking in such complex adaptations. Here, we identify cis-acting modifications with the help of an interspecific crossing scheme designed to distinguish modifications derived in each of the two sister species, Arabidopsis halleri and A. lyrata Allele-specific expression levels were assessed in three environmental conditions chosen to reflect interspecific ecological differences: cold exposure, dehydration, and standard conditions. The functions described by Gene Ontology categories enriched in cis-acting mutations are markedly different in A. halleri and A. lyrata, suggesting that polygenic adaptation reshaped distinct polygenic molecular functions in the two species. In the A. halleri lineage, an excess of cis-acting changes affecting metal transport and homeostasis was observed, confirming that the well-known heavy metal tolerance of this species is the result of polygenic selection. In A. lyrata, we find a marked excess of cis-acting changes among genes showing a transcriptional response to cold stress in the outgroup species A. thaliana The adaptive relevance of these changes will have to be validated. We finally observed that polygenic molecular functions enriched in derived cis acting changes are more constrained at the amino acid level. Using the distribution of cis-acting variation to tackle the polygenic basis of adaptation thus reveals the contribution of mutations of small effect to Darwinian adaptation. PMID- 27189538 TI - Conservation and Innovation of APOBEC3A Restriction Functions during Primate Evolution. AB - LINE-1 (long interspersed element-1) retroelements are the only active autonomous endogenous retroelements in human genomes. Their retrotransposition activity has created close to 50% of the current human genome. Due to the apparent costs of this proliferation, host genomes have evolved multiple mechanisms to curb LINE-1 retrotransposition. Here, we investigate the evolution and function of the LINE-1 restriction factor APOBEC3A, a member of the APOBEC3 cytidine deaminase gene family. We find that APOBEC3A genes have evolved rapidly under diversifying selection in primates, suggesting changes in APOBEC3A have been recurrently selected in a host-pathogen "arms race." Nonetheless, in contrast to previous reports, we find that the LINE-1 restriction activity of APOBEC3A proteins has been strictly conserved throughout simian primate evolution in spite of its pervasive diversifying selection. Based on these results, we conclude that LINE 1s have not driven the rapid evolution of APOBEC3A in primates. In contrast to this conserved LINE-1 restriction, we find that a subset of primate APOBEC3A genes have enhanced antiviral restriction. We trace this gain of antiviral restriction in APOBEC3A to the common ancestor of a subset of Old World monkeys. Thus, APOBEC3A has not only maintained its LINE-1 restriction ability, but also evolved a gain of antiviral specificity against other pathogens. Our findings suggest that while APOBEC3A has evolved to restrict additional pathogens, only those adaptive amino acid changes that leave LINE-1 restriction unperturbed have been tolerated. PMID- 27189542 TI - SpreaD3: Interactive Visualization of Spatiotemporal History and Trait Evolutionary Processes. AB - Model-based phylogenetic reconstructions increasingly consider spatial or phenotypic traits in conjunction with sequence data to study evolutionary processes. Alongside parameter estimation, visualization of ancestral reconstructions represents an integral part of these analyses. Here, we present a complete overhaul of the spatial phylogenetic reconstruction of evolutionary dynamics software, now called SpreaD3 to emphasize the use of data-driven documents, as an analysis and visualization package that primarily complements Bayesian inference in BEAST (http://beast.bio.ed.ac.uk, last accessed 9 May 2016). The integration of JavaScript D3 libraries (www.d3.org, last accessed 9 May 2016) offers novel interactive web-based visualization capacities that are not restricted to spatial traits and extend to any discrete or continuously valued trait for any organism of interest. PMID- 27189541 TI - Evolution of Vertebrate Phototransduction: Cascade Activation. AB - We applied high-throughput sequencing to eye tissue from several species of basal vertebrates (a hagfish, two species of lamprey, and five species of gnathostome fish), and we analyzed the mRNA sequences for the proteins underlying activation of the phototransduction cascade. The molecular phylogenies that we constructed from these sequences are consistent with the 2R WGD model of two rounds of whole genome duplication. Our analysis suggests that agnathans retain an additional representative (that has been lost in gnathostomes) in each of the gene families we studied; the evidence is strong for the G-protein alpha subunit (GNAT) and the cGMP phosphodiesterase (PDE6), and indicative for the cyclic nucleotide-gated channels (CNGA and CNGB). Two of the species (the hagfish Eptatretus cirrhatus and the lamprey Mordacia mordax) possess only a single class of photoreceptor, simplifying deductions about the composition of cascade protein isoforms utilized in their photoreceptors. For the other lamprey, Geotria australis, analysis of the ratios of transcript levels in downstream and upstream migrant animals permits tentative conclusions to be drawn about the isoforms used in four of the five spectral classes of photoreceptor. Overall, our results suggest that agnathan rod-like photoreceptors utilize the same GNAT1 as gnathostomes, together with a homodimeric PDE6 that may be agnathan-specific, whereas agnathan cone-like photoreceptors utilize a GNAT that may be agnathan-specific, together with the same PDE6C as gnathostomes. These findings help elucidate the evolution of the vertebrate phototransduction cascade from an ancestral chordate phototransduction cascade that existed prior to the vertebrate radiation. PMID- 27189543 TI - Regulatory Differences in Natal Down Development between Altricial Zebra Finch and Precocial Chicken. AB - Birds can be classified into altricial and precocial. The hatchlings of altricial birds are almost naked, whereas those of precocial birds are covered with natal down. This regulatory divergence is thought to reflect environmental adaptation, but the molecular basis of the divergence is unclear. To address this issue, we chose the altricial zebra finch and the precocial chicken as the model animals. We noted that zebra finch hatchlings show natal down growth suppressed anterior dorsal (AD) skin but partially down-covered posterior dorsal (PD) skin. Comparing the transcriptomes of AD and PD skins, we found that the feather growth promoter SHH (sonic hedgehog) was expressed higher in PD skin than in AD skin. Moreover, the data suggested that the FGF (fibroblast growth factor)/Mitogen-activated protein kinase (MAPK) signaling pathway is involved in natal down growth suppression and that FGF16 is a candidate upstream signaling suppressor. Ectopic expression of FGF16 on chicken leg skin showed downregulation of SHH, upregulation of the feather growth suppressor FGF10, and suppression of feather bud elongation, similar to the phenotype found in zebra finch embryonic AD skin. Therefore, we propose that FGF16-related signals suppress natal down elongation and cause the naked AD skin in zebra finch. Our study provides insights into the regulatory divergence in natal down formation between precocial and altricial birds. PMID- 27189545 TI - A Simple, General Result for the Variance of Substitution Number in Molecular Evolution. AB - The number of substitutions (of nucleotides, amino acids, etc.) that take place during the evolution of a sequence is a stochastic variable of fundamental importance in the field of molecular evolution. Although the mean number of substitutions during molecular evolution of a sequence can be estimated for a given substitution model, no simple solution exists for the variance of this random variable. We show in this article that the computation of the variance is as simple as that of the mean number of substitutions for both short and long times. Apart from its fundamental importance, this result can be used to investigate the dispersion index R, that is, the ratio of the variance to the mean substitution number, which is of prime importance in the neutral theory of molecular evolution. By investigating large classes of substitution models, we demonstrate that although [Formula: see text], to obtain R significantly larger than unity necessitates in general additional hypotheses on the structure of the substitution model. PMID- 27189546 TI - Estimating the Frequency of Horizontal Gene Transfer Using Phylogenetic Models of Gene Gain and Loss. AB - We analyze patterns of gene presence and absence in a maximum likelihood framework with rate parameters for gene gain and loss. Standard methods allow independent gains and losses in different parts of a tree. While losses of the same gene are likely to be frequent, multiple gains need to be considered carefully. A gene gain could occur by horizontal transfer or by origin of a gene within the lineage being studied. If a gene is gained more than once, then at least one of these gains must be a horizontal transfer. A key parameter is the ratio of gain to loss rates, a/v We consider the limiting case known as the infinitely many genes model, where a/v tends to zero and a gene cannot be gained more than once. The infinitely many genes model is used as a null model in comparison to models that allow multiple gains. Using genome data from cyanobacteria and archaea, it is found that the likelihood is significantly improved by allowing for multiple gains, but the average a/v is very small. The fraction of genes whose presence/absence pattern is best explained by multiple gains is only 15% in the cyanobacteria and 20% and 39% in two data sets of archaea. The distribution of rates of gene loss is very broad, which explains why many genes follow a treelike pattern of vertical inheritance, despite the presence of a significant minority of genes that undergo horizontal transfer. PMID- 27189544 TI - Adaptation by Deletogenic Replication Slippage in a Nascent Symbiont. AB - As a consequence of population level constraints in the obligate, host-associated lifestyle, intracellular symbiotic bacteria typically exhibit high rates of molecular sequence evolution and extensive genome degeneration over the course of their host association. While the rationale for genome degeneration is well understood, little is known about the molecular mechanisms driving this change. To understand these mechanisms we compared the genome of Sodalis praecaptivus, a nonhost associated bacterium that is closely related to members of the Sodalis allied clade of insect endosymbionts, with the very recently derived insect symbiont Candidatus Sodalis pierantonius. The characterization of indel mutations in the genome of Ca Sodalis pierantonius shows that the replication system in this organism is highly prone to deletions resulting from polymerase slippage events in regions encoding G+C-rich repetitive sequences. This slippage-prone phenotype is mechanistically associated with the loss of certain components of the bacterial DNA recombination machinery at an early stage in symbiotic life and is expected to facilitate rapid adaptation to the novel host environment. This is analogous to the emergence of mutator strains in both natural and laboratory populations of bacteria, which tend to reach high frequencies in clonal populations due to linkage between the mutator allele and the resulting adaptive mutations. PMID- 27189547 TI - Fast Coalescent-Based Computation of Local Branch Support from Quartet Frequencies. AB - Species tree reconstruction is complicated by effects of incomplete lineage sorting, commonly modeled by the multi-species coalescent model (MSC). While there has been substantial progress in developing methods that estimate a species tree given a collection of gene trees, less attention has been paid to fast and accurate methods of quantifying support. In this article, we propose a fast algorithm to compute quartet-based support for each branch of a given species tree with regard to a given set of gene trees. We then show how the quartet support can be used in the context of the MSC to compute (1) the local posterior probability (PP) that the branch is in the species tree and (2) the length of the branch in coalescent units. We evaluate the precision and recall of the local PP on a wide set of simulated and biological datasets, and show that it has very high precision and improved recall compared with multi-locus bootstrapping. The estimated branch lengths are highly accurate when gene tree estimation error is low, but are underestimated when gene tree estimation error increases. Computation of both the branch length and local PP is implemented as new features in ASTRAL. PMID- 27189549 TI - Sperm Bindin Divergence under Sexual Selection and Concerted Evolution in Sea Stars. AB - Selection associated with competition among males or sexual conflict between mates can create positive selection for high rates of molecular evolution of gamete recognition genes and lead to reproductive isolation between species. We analyzed coding sequence and repetitive domain variation in the gene encoding the sperm acrosomal protein bindin in 13 diverse sea star species. We found that bindin has a conserved coding sequence domain structure in all 13 species, with several repeated motifs in a large central region that is similar among all sea stars in organization but highly divergent among genera in nucleotide and predicted amino acid sequence. More bindin codons and lineages showed positive selection for high relative rates of amino acid substitution in genera with gonochoric outcrossing adults (and greater expected strength of sexual selection) than in selfing hermaphrodites. That difference is consistent with the expectation that selfing (a highly derived mating system) may moderate the strength of sexual selection and limit the accumulation of bindin amino acid differences. The results implicate both positive selection on single codons and concerted evolution within the repetitive region in bindin divergence, and suggest that both single amino acid differences and repeat differences may affect sperm-egg binding and reproductive compatibility. PMID- 27189550 TI - Expanded Genetic Codes Create New Mutational Routes to Rifampicin Resistance in Escherichia coli. AB - Until recently, evolutionary questions surrounding the nature of the genetic code have been mostly limited to the realm of conjecture, modeling, and simulation due to the difficulty of altering this fundamental property of living organisms. Concerted genome and protein engineering efforts now make it possible to experimentally study the impact of alternative genetic codes on the evolution of biological systems. We explored how Escherichia coli strains that incorporate a 21st nonstandard amino acid (nsAA) at the recoded amber (TAG) stop codon evolve resistance to the antibiotic rifampicin. Resistance to rifampicin arises from chromosomal mutations in the beta subunit of RNA polymerase (RpoB). We found that a variety of mutations that lead to substitutions of nsAAs in the essential RpoB protein confer robust rifampicin resistance. We interpret these results in a framework in which an expanded code can increase evolvability in two distinct ways: by adding a new letter with unique chemical properties to the protein alphabet and by altering the mutational connectivity of amber-adjacent codons by converting a lethal nonsense mutation into a missense mutation. Finally, we consider the implications of these results for the evolution of alternative genetic codes. In our experiments, reliance on a mutation to a reassigned codon for a vital trait is not required for the long-term maintenance of an expanded genetic code and may even destabilize incorporation of an nsAA, a result that is consistent with the codon capture model of genetic code evolution. PMID- 27189548 TI - Phylogenetic and Genomic Analyses Resolve the Origin of Important Plant Genes Derived from Transposable Elements. AB - Once perceived as merely selfish, transposable elements (TEs) are now recognized as potent agents of adaptation. One way TEs contribute to evolution is through TE exaptation, a process whereby TEs, which persist by replicating in the genome, transform into novel host genes, which persist by conferring phenotypic benefits. Known exapted TEs (ETEs) contribute diverse and vital functions, and may facilitate punctuated equilibrium, yet little is known about this process. To better understand TE exaptation, we designed an approach to resolve the phylogenetic context and timing of exaptation events and subsequent patterns of ETE diversification. Starting with known ETEs, we search in diverse genomes for basal ETEs and closely related TEs, carefully curate the numerous candidate sequences, and infer detailed phylogenies. To distinguish TEs from ETEs, we also weigh several key genomic characteristics including repetitiveness, terminal repeats, pseudogenic features, and conserved domains. Applying this approach to the well-characterized plant ETEs MUG and FHY3, we show that each group is paraphyletic and we argue that this pattern demonstrates that each originated in not one but multiple exaptation events. These exaptations and subsequent ETE diversification occurred throughout angiosperm evolution including the crown group expansion, the angiosperm radiation, and the primitive evolution of angiosperms. In addition, we detect evidence of several putative novel ETE families. Our findings support the hypothesis that TE exaptation generates novel genes more frequently than is currently thought, often coinciding with key periods of evolution. PMID- 27189551 TI - Genomic Profiles of Diversification and Genotype-Phenotype Association in Island Nematode Lineages. AB - Understanding how new species form requires investigation of evolutionary forces that cause phenotypic and genotypic changes among populations. However, the mechanisms underlying speciation vary and little is known about whether genomes diversify in the same ways in parallel at the incipient scale. We address this using the nematode, Pristionchus pacificus, which resides at an interesting point on the speciation continuum (distinct evolutionary lineages without reproductive isolation), and inhabits heterogeneous environments subject to divergent environmental pressures. Using whole genome re-sequencing of 264 strains, we estimate FST to identify outlier regions of extraordinary differentiation (~1.725 Mb of the 172.5 Mb genome). We find evidence for shared divergent genomic regions occurring at a higher frequency than expected by chance among populations of the same evolutionary lineage. We use allele frequency spectra to find that, among lineages, 53% of divergent regions are consistent with adaptive selection, whereas 24% and 23% of such regions suggest background selection and restricted gene flow, respectively. In contrast, among populations from the same lineage, similar proportions (34-48%) of divergent regions correspond to adaptive selection and restricted gene flow, whereas 13-22% suggest background selection. Because speciation often involves phenotypic and genomic divergence, we also evaluate phenotypic variation, focusing on pH tolerance, which we find is diverging in a manner corresponding to environmental differences among populations. Taking a genome-wide association approach, we functionally validate a significant genotype-phenotype association for this trait. Our results are consistent with P. pacificus undergoing heterogeneous genotypic and phenotypic diversification related to both evolutionary and environmental processes. PMID- 27189552 TI - A Lesson from Wheat Evolution: Wild and Landraces Genetic Diversity the Key to Improving the Nutritional Value of Our Spaghetti Dish. PMID- 27189553 TI - MEGA Evolutionary Software Re-Engineered to Handle Today's Big Data Demands. PMID- 27189554 TI - Are We What We Eat? Evidence of a Vegetarian Diet Permanently Shaping the Human Genome to Change Individual Risk of Cancer and Heart Disease. PMID- 27189555 TI - The Nuanced Interplay of Intrinsic Disorder and Other Structural Properties Driving Protein Evolution. AB - Protein evolution often occurs at unequal rates in different sites along an amino acid chain. Site-specific evolutionary rates have been linked to several structural and functional properties of proteins. Previous analyses of this phenomenon have involved relatively small datasets and, in some cases, the interaction among multiple structural factors is not evaluated. Here, we present the results of a large-scale phylogenetic and statistical analysis, testing the effects and interactions of three structural properties on amino acid replacement rates. We used sequence-based computational methods to predict (i) intrinsic disorder propensity, (ii) secondary structure, and (iii) functional domain involvement across millions of amino acid sites in thousands of sequence alignments of metazoan proteins. Our results somewhat corroborate earlier findings that intrinsically disordered sites tend to be more variable than ordered sites, but there is considerable overlap among their rate distributions, and a significant confounding interaction exists between intrinsic disorder and secondary structure. Notably, protein sites that are consistently predicted to be both intrinsically disordered and involved in secondary structures tend to be the most conserved at the amino acid level, suggesting that they are highly constrained and functionally important. In addition, a significant interaction exists between functional domain involvement and secondary structure. These findings suggest that multiple structural drivers of protein evolution should be evaluated simultaneously in order to get a clear picture of their individual effects as well as any confounding interactions among them. PMID- 27189556 TI - RiboDB Database: A Comprehensive Resource for Prokaryotic Systematics. AB - Ribosomal proteins (r-proteins) are increasingly used as an alternative to ribosomal rRNA for prokaryotic systematics. However, their routine use is difficult because r-proteins are often not or wrongly annotated in complete genome sequences, and there is currently no dedicated exhaustive database of r proteins. RiboDB aims at fulfilling this gap. This weekly updated comprehensive database allows the fast and easy retrieval of r-protein sequences from publicly available complete prokaryotic genome sequences. The current version of RiboDB contains 90 r-proteins from 3,750 prokaryotic complete genomes encompassing 38 phyla/major classes and 1,759 different species. RiboDB is accessible at http://ribodb.univ-lyon1.fr and through ACNUC interfaces. PMID- 27189557 TI - Searching the Evolutionary Origin of Epithelial Mucus Protein Components-Mucins and FCGBP. AB - The gel-forming mucins are large glycosylated proteins that are essential components of the mucus layers covering epithelial cells. Using novel methods of identifying mucins based on profile hidden Markov models, we have found a large number of such proteins in Metazoa, aiding in their classification and allowing evolutionary studies. Most vertebrates have 5-6 gel-forming mucin genes and the genomic arrangement of these genes is well conserved throughout vertebrates. An exception is the frog Xenopus tropicalis with an expanded repertoire of at least 26 mucins of this type. Furthermore, we found that the ovomucin protein, originally identified in chicken, is characteristic of reptiles, birds, and amphibians. Muc6 is absent in teleost fish, but we now show that it is present in animals such as ghost sharks, demonstrating an early origin in vertebrate evolution. Public RNA-Seq data were analyzed with respect to mucins in zebrafish, frog, and chicken, thus allowing comparison in regard of tissue and developmental specificity. Analyses of invertebrate proteins reveal that gel-forming-mucin type of proteins is widely distributed also in this group. Their presence in Cnidaria, Porifera, and in Ctenophora (comb jellies) shows that these proteins were present early in metazoan evolution. Finally, we examined the evolution of the FCGBP protein, abundant in mucus and related to gel-forming mucins in terms of structure and localization. We demonstrate that FCGBP, ubiquitous in vertebrates, has a conserved N-terminal domain. Interestingly, this domain is also present as an N-terminal sequence in a number of bacterial proteins. PMID- 27189561 TI - Phylo.io: Interactive Viewing and Comparison of Large Phylogenetic Trees on the Web. AB - Phylogenetic trees are pervasively used to depict evolutionary relationships. Increasingly, researchers need to visualize large trees and compare multiple large trees inferred for the same set of taxa (reflecting uncertainty in the tree inference or genuine discordance among the loci analyzed). Existing tree visualization tools are however not well suited to these tasks. In particular, side-by-side comparison of trees can prove challenging beyond a few dozen taxa. Here, we introduce Phylo.io, a web application to visualize and compare phylogenetic trees side-by-side. Its distinctive features are: highlighting of similarities and differences between two trees, automatic identification of the best matching rooting and leaf order, scalability to large trees, high usability, multiplatform support via standard HTML5 implementation, and possibility to store and share visualizations. The tool can be freely accessed at http://phylo.io and can easily be embedded in other web servers. The code for the associated JavaScript library is available at https://github.com/DessimozLab/phylo-io under an MIT open source license. PMID- 27189558 TI - A Recent Whole-Genome Duplication Divides Populations of a Globally Distributed Microsporidian. AB - The Microsporidia are a major group of intracellular fungi and important parasites of animals including insects, fish, and immunocompromised humans. Microsporidian genomes have undergone extreme reductive evolution but there are major differences in genome size and structure within the group: some are prokaryote-like in size and organisation (<3 Mb of gene-dense sequence) while others have more typically eukaryotic genome architectures. To gain fine-scale, population-level insight into the evolutionary dynamics of these tiny eukaryotic genomes, we performed the broadest microsporidian population genomic study to date, sequencing geographically isolated strains of Spraguea, a marine microsporidian infecting goosefish worldwide. Our analysis revealed that population structure across the Atlantic Ocean is associated with a conserved difference in ploidy, with American and Canadian isolates sharing an ancestral whole genome duplication that was followed by widespread pseudogenisation and sorting-out of paralogue pairs. While past analyses have suggested de novo gene formation of microsporidian-specific genes, we found evidence for the origin of new genes from noncoding sequence since the divergence of these populations. Some of these genes experience selective constraint, suggesting the evolution of new functions and local host adaptation. Combining our data with published microsporidian genomes, we show that nucleotide composition across the phylum is shaped by a mutational bias favoring A and T nucleotides, which is opposed by an evolutionary force favoring an increase in genomic GC content. This study reveals ongoing dramatic reorganization of genome structure and the evolution of new gene functions in modern microsporidians despite extensive genomic streamlining in their common ancestor. PMID- 27189562 TI - How Common Is Parallel Intron Gain? Rapid Evolution Versus Independent Creation in Recently Created Introns in Daphnia. AB - The evolutionary history of the spliceosomal introns that interrupt nuclear genes in eukaryotes has been debated for four decades. Positions of introns show a high degree of coincidence between various eukaryotes, implying either than many modern introns are very old and/or that intron creation is highly biased toward certain sites, leading to rampant parallel intron gain. A series of articles in this and other journals reported evidence for a strikingly high degree of parallel insertion of introns in different alleles of the water flea Daphnia pulex Here, I report several new analyses of these data. Among the 23 loci reported to be undergoing parallel intron gain, I find that in five cases introns reported to be unrelated show extended sequence similarity strongly suggesting that the introns are in fact homologous. Five additional cases show extended conserved motifs between allegedly unrelated introns. For nearly all loci including the 13 remaining loci, at least one intron shows hallmarks of rapid sequence evolution, thwarting confident inference about homology. In addition, I reanalyze gene trees reconstructed from flanking exonic sequences, claimed by the original authors as additional evidence for parallel gain. I show that these phylogenetic trees frequently fail to recover expected relationships, and in any case show relationships not consistent with parallel intron gains. In total, I conclude that the data do not support widespread parallel intron gain in D. pulex These findings strengthen the notion that shared intron positions generally reflect ancestral introns, and thus the notion of complex genes in early eukaryotes. PMID- 27189560 TI - Target-Driven Positive Selection at Hot Spots of Scorpion Toxins Uncovers Their Potential in Design of Insecticides. AB - Positive selection sites (PSSs), a class of amino acid sites with an excess of nonsynonymous to synonymous substitutions, are indicators of adaptive molecular evolution and have been detected in many protein families involved in a diversity of biological processes by statistical approaches. However, few studies are conducted to evaluate their functional significance and the driving force behind the evolution (i.e., agent of selection). Scorpion alpha-toxins are a class of multigene family of peptide neurotoxins affecting voltage-gated Na(+ )(Nav) channels, whose members exhibit differential potency and preference for insect and mammalian Nav channels. In this study, we undertook a systematical molecular dissection of nearly all the PSSs newly characterized in the Mesobuthus alpha toxin family and a two-residue insertion ((19)AlaPhe(20)) located within a positively selected loop via mutational analysis of alpha-like MeuNaTxalpha-5, one member affecting both insect and mammalian Nav channels. This allows to identify hot-spot residues on its functional face involved in interaction with the receptor site of Nav channels, which comprises two PSSs (Ile(40) and Leu(41)) and the small insertion, both located on two spatially separated functional loops. Mutations at these hot-spots resulted in a remarkably decreased anti mammalian activity in MeuNaTxalpha-5 with partially impaired or enhanced insecticide activity, suggesting the potential of PSSs in designing promising candidate insecticides from scorpion alpha-like toxins. Based on an experiment guided toxin-channel complex model and high evolutionary variability in the receptor site of predators and prey of scorpions, we provide new evidence for target-driven adaptive evolution of scorpion toxins to deal with their targets' diversity. PMID- 27189559 TI - Evolutionary Metabolomics Reveals Domestication-Associated Changes in Tetraploid Wheat Kernels. AB - Domestication and breeding have influenced the genetic structure of plant populations due to selection for adaptation from natural habitats to agro ecosystems. Here, we investigate the effects of selection on the contents of 51 primary kernel metabolites and their relationships in three Triticum turgidum L. subspecies (i.e., wild emmer, emmer, durum wheat) that represent the major steps of tetraploid wheat domestication. We present a methodological pipeline to identify the signature of selection for molecular phenotypic traits (e.g., metabolites and transcripts). Following the approach, we show that a reduction in unsaturated fatty acids was associated with selection during domestication of emmer (primary domestication). We also show that changes in the amino acid content due to selection mark the domestication of durum wheat (secondary domestication). These effects were found to be partially independent of the associations that unsaturated fatty acids and amino acids have with other domestication-related kernel traits. Changes in contents of metabolites were also highlighted by alterations in the metabolic correlation networks, indicating wide metabolic restructuring due to domestication. Finally, evidence is provided that wild and exotic germplasm can have a relevant role for improvement of wheat quality and nutritional traits. PMID- 27189563 TI - Evolutionary Consequences of DNA Methylation in a Basal Metazoan. AB - Gene body methylation (gbM) is an ancestral and widespread feature in Eukarya, yet its adaptive value and evolutionary implications remain unresolved. The occurrence of gbM within protein-coding sequences is particularly puzzling, because methylation causes cytosine hypermutability and hence is likely to produce deleterious amino acid substitutions. We investigate this enigma using an evolutionarily basal group of Metazoa, the stony corals (order Scleractinia, class Anthozoa, phylum Cnidaria). We show that patterns of coral gbM are similar to other invertebrate species, predicting wide and active transcription and slower sequence evolution. We also find a strong correlation between gbM and codon bias, resulting from systematic replacement of CpG bearing codons. We conclude that gbM has strong effects on codon evolution and speculate that this may influence establishment of optimal codons. PMID- 27189565 TI - TriLoNet: Piecing Together Small Networks to Reconstruct Reticulate Evolutionary Histories. AB - Phylogenetic networks are a generalization of evolutionary trees that can be used to represent reticulate processes such as hybridization and recombination. Here, we introduce a new approach called TriLoNet (Trinet Level- one Network algorithm) to construct such networks directly from sequence alignments which works by piecing together smaller phylogenetic networks. More specifically, using a bottom up approach similar to Neighbor-Joining, TriLoNet constructs level-1 networks (networks that are somewhat more general than trees) from smaller level-1 networks on three taxa. In simulations, we show that TriLoNet compares well with Lev1athan, a method for reconstructing level-1 networks from three-leaved trees. In particular, in simulations we find that Lev1athan tends to generate networks that overestimate the number of reticulate events as compared with those generated by TriLoNet. We also illustrate TriLoNet's applicability using simulated and real sequence data involving recombination, demonstrating that it has the potential to reconstruct informative reticulate evolutionary histories. TriLoNet has been implemented in JAVA and is freely available at https://www.uea.ac.uk/computing/TriLoNet. PMID- 27189564 TI - How Good Are Statistical Models at Approximating Complex Fitness Landscapes? AB - Fitness landscapes determine the course of adaptation by constraining and shaping evolutionary trajectories. Knowledge of the structure of a fitness landscape can thus predict evolutionary outcomes. Empirical fitness landscapes, however, have so far only offered limited insight into real-world questions, as the high dimensionality of sequence spaces makes it impossible to exhaustively measure the fitness of all variants of biologically meaningful sequences. We must therefore revert to statistical descriptions of fitness landscapes that are based on a sparse sample of fitness measurements. It remains unclear, however, how much data are required for such statistical descriptions to be useful. Here, we assess the ability of regression models accounting for single and pairwise mutations to correctly approximate a complex quasi-empirical fitness landscape. We compare approximations based on various sampling regimes of an RNA landscape and find that the sampling regime strongly influences the quality of the regression. On the one hand it is generally impossible to generate sufficient samples to achieve a good approximation of the complete fitness landscape, and on the other hand systematic sampling schemes can only provide a good description of the immediate neighborhood of a sequence of interest. Nevertheless, we obtain a remarkably good and unbiased fit to the local landscape when using sequences from a population that has evolved under strong selection. Thus, current statistical methods can provide a good approximation to the landscape of naturally evolving populations. PMID- 27189567 TI - Dynamic Evolution of Nitric Oxide Detoxifying Flavohemoglobins, a Family of Single-Protein Metabolic Modules in Bacteria and Eukaryotes. AB - Due to their functional independence, proteins that comprise standalone metabolic units, which we name single-protein metabolic modules, may be particularly prone to gene duplication (GD) and horizontal gene transfer (HGT). Flavohemoglobins (flavoHbs) are prime examples of single-protein metabolic modules, detoxifying nitric oxide (NO), a ubiquitous toxin whose antimicrobial properties many life forms exploit, to nitrate, a common source of nitrogen for organisms. FlavoHbs appear widespread in bacteria and have been identified in a handful of microbial eukaryotes, but how the distribution of this ecologically and biomedically important protein family evolved remains unknown. Reconstruction of the evolutionary history of 3,318 flavoHb protein sequences covering the family's known diversity showed evidence of recurrent HGT at multiple evolutionary scales including intrabacterial HGT, as well as HGT from bacteria to eukaryotes. One of the most striking examples of HGT is the acquisition of a flavoHb by the dandruff and eczema-causing fungus Malassezia from Corynebacterium Actinobacteria, a transfer that growth experiments show is capable of mediating NO resistance in fungi. Other flavoHbs arose via GD; for example, many filamentous fungi possess two flavoHbs that are differentially targeted to the cytosol and mitochondria, likely conferring protection against external and internal sources of NO, respectively. Because single-protein metabolic modules such as flavoHb function independently, readily undergo GD and HGT, and are frequently involved in organismal defense and competition, we suggest that they represent "plug-and play" proteins for ecological arms races. PMID- 27189566 TI - Pervasive Effects of Aging on Gene Expression in Wild Wolves. AB - Gene expression levels change as an individual ages and responds to environmental conditions. With the exception of humans, such patterns have principally been studied under controlled conditions, overlooking the array of developmental and environmental influences that organisms encounter under conditions in which natural selection operates. We used high-throughput RNA sequencing (RNA-Seq) of whole blood to assess the relative impacts of social status, age, disease, and sex on gene expression levels in a natural population of gray wolves (Canis lupus). Our findings suggest that age is broadly associated with gene expression levels, whereas other examined factors have minimal effects on gene expression patterns. Further, our results reveal evolutionarily conserved signatures of senescence, such as immunosenescence and metabolic aging, between wolves and humans despite major differences in life history and environment. The effects of aging on gene expression levels in wolves exhibit conservation with humans, but the more rapid expression differences observed in aging wolves is evolutionarily appropriate given the species' high level of extrinsic mortality due to intraspecific aggression. Some expression changes that occur with age can facilitate physical age-related changes that may enhance fitness in older wolves. However, the expression of these ancestral patterns of aging in descendant modern dogs living in highly modified domestic environments may be maladaptive and cause disease. This work provides evolutionary insight into aging patterns observed in domestic dogs and demonstrates the applicability of studying natural populations to investigate the mechanisms of aging. PMID- 27189569 TI - Insertion DNA Accelerates Meiotic Interchromosomal Recombination in Arabidopsis thaliana. AB - Nucleotide insertions/deletions are ubiquitous in eukaryotic genomes, and the resulting hemizygous (unpaired) DNA has significant, heritable effects on adjacent DNA. However, little is known about the genetic behavior of insertion DNA. Here, we describe a binary transgenic system to study the behavior of insertion DNA during meiosis. Transgenic Arabidopsis lines were generated to carry two different defective reporter genes on nonhomologous chromosomes, designated as "recipient" and "donor" lines. Double hemizygous plants (harboring unpaired DNA) were produced by crossing between the recipient and the donor, and double homozygous lines (harboring paired DNA) via self-pollination. The transfer of the donor's unmutated sequence to the recipient generated a functional beta glucuronidase gene, which could be visualized by histochemical staining and corroborated by polymerase chain reaction amplification and sequencing. More than 673 million seedlings were screened, and the results showed that meiotic ectopic recombination in the hemizygous lines occurred at a frequency >6.49-fold higher than that in the homozygous lines. Gene conversion might have been exclusively or predominantly responsible for the gene correction events. The direct measurement of ectopic recombination events provided evidence that an insertion, in the absence of an allelic counterpart, could scan the entire genome for homologous counterparts with which to pair. Furthermore, the unpaired (hemizygous) architectures could accelerate ectopic recombination between itself and interchromosomal counterparts. We suggest that the ectopic recombination accelerated by hemizygous architectures may be a general mechanism for interchromosomal recombination through ubiquitously dispersed repeat sequences in plants, ultimately contributing to genetic renovation and eukaryotic evolution. PMID- 27189568 TI - microRNAs in the Same Clusters Evolve to Coordinately Regulate Functionally Related Genes. AB - MicroRNAs (miRNAs) are endogenously expressed small noncoding RNAs. The genomic locations of animal miRNAs are significantly clustered in discrete loci. We found duplication and de novo formation were important mechanisms to create miRNA clusters and the clustered miRNAs tend to be evolutionarily conserved. We proposed a "functional co-adaptation" model to explain how clustering helps newly emerged miRNAs survive and develop functions. We presented evidence that abundance of miRNAs in the same clusters were highly correlated and those miRNAs exerted cooperative repressive effects on target genes in human tissues. By transfecting miRNAs into human and fly cells and extensively profiling the transcriptome alteration with deep-sequencing, we further demonstrated the functional co-adaptation between new and old miRNAs in the miR-17-92 cluster. Our population genomic analysis suggest that positive Darwinian selection might be the driving force underlying the formation and evolution of miRNA clustering. Our model provided novel insights into mechanisms and evolutionary significance of miRNA clustering. PMID- 27189571 TI - Nondegenerative Evolution in Ancient Heritable Bacterial Endosymbionts of Fungi. AB - Bacterial endosymbionts are critical to the existence of many eukaryotes. Among them, vertically transmitted endobacteria are uniquely typified by reduced genomes and molecular evolution rate acceleration relative to free-living taxa. These patterns are attributable to genetic drift-dominated degenerative processes associated with reproductive dependence on the host. The degenerative evolution scenario is well supported in endobacteria with strict vertical transmission, such as essential mutualists of insects. In contrast, heritable endosymbionts that are nonessential to their hosts and engage occasionally in horizontal transmission are expected to display deviations from the degenerative evolution model. To explore evolution patterns in such nonessential endobacteria, we focused on Candidatus Glomeribacter gigasporarum ancient heritable mutualists of fungi. Using a collection of genomes, we estimated in Glomeribacter mutation rate at 2.03 * 10(-9) substitutions per site per year and effective population size at 1.44 * 10(8) Both fall within the range of values observed in free-living bacteria. To assess the ability of Glomeribacter to purge slightly deleterious mutations, we examined genome-wide dN/dS values and distribution patterns. We found that these dN/dS profiles cluster Glomeribacter with free-living bacteria as well as with other nonessential endosymbionts, while distinguishing it from essential heritable mutualists of insects. Finally, our evolutionary simulations revealed that the molecular evolution rate acceleration in Glomeribacter is caused by limited recombination in a largely clonal population rather than by increased fixation of slightly deleterious mutations. Based on these patterns, we propose that genome evolution in Glomeribacter is nondegenerative and exemplifies a departure from the model of degenerative evolution in heritable endosymbionts. PMID- 27189570 TI - Characterization of the Cadherin-Catenin Complex of the Sea Anemone Nematostella vectensis and Implications for the Evolution of Metazoan Cell-Cell Adhesion. AB - The cadherin-catenin complex (CCC) mediates cell-cell adhesion in bilaterian animals by linking extracellular cadherin-based adhesions to the actin cytoskeleton. However, it is unknown whether the basic organization of the complex is conserved across all metazoans. We tested whether protein interactions and actin-binding properties of the CCC are conserved in a nonbilaterian animal, the sea anemone Nematostella vectensis We demonstrated that N. vectensis has a complete repertoire of cadherin-catenin proteins, including two classical cadherins, one alpha-catenin, and one beta-catenin. Using size-exclusion chromatography and multi-angle light scattering, we showed that alpha-catenin and beta-catenin formed a heterodimer that bound N. vectensis Cadherin-1 and -2. Nematostella vectensis alpha-catenin bound F-actin with equivalent affinity as either a monomer or an alpha/beta-catenin heterodimer, and its affinity for F actin was, in part, regulated by a novel insert between the N- and C-terminal domains. Nematostella vectensis alpha-catenin inhibited Arp2/3 complex-mediated nucleation of actin filaments, a regulatory property previously thought to be unique to mammalian alphaE-catenin. Thus, despite significant differences in sequence, the key interactions of the CCC are conserved between bilaterians and cnidarians, indicating that the core function of the CCC as a link between cell adhesions and the actin cytoskeleton is ancestral in the eumetazoans. PMID- 27189572 TI - Functional Conservation and Divergence of daf-22 Paralogs in Pristionchus pacificus Dauer Development. AB - Small-molecule signaling in nematode dauer formation has emerged as a major model to study chemical communication in development and evolution. Developmental arrest as nonfeeding and stress-resistant dauer larvae represents the major survival and dispersal strategy. Detailed studies in Caenorhabditis elegans and Pristionchus pacificus revealed that small-molecule communication changes rapidly in evolution resulting in extreme structural diversity of small-molecule compounds. In C. elegans, a blend of ascarosides constitutes the dauer pheromone, whereas the P. pacificus dauer pheromone includes additional paratosides and integrates building blocks from diverse primary metabolic pathways. Despite this complexity of small-molecule structures and functions, little is known about the biosynthesis of small molecules in nematodes outside C. elegans Here, we show that the genes encoding enzymes of the peroxisomal beta-oxidation pathway involved in small-molecule biosynthesis evolve rapidly, including gene duplications and domain switching. The thiolase daf-22, the most downstream factor in C. elegans peroxisomal beta-oxidation, has duplicated in P. pacificus, resulting in Ppa-daf-22.1, which still contains the sterol-carrier-protein (SCP) domain that was lost in C. elegans daf-22, and Ppa-daf-22.2. Using the CRISPR/Cas9 system, we induced mutations in both P. pacificus daf-22 genes and identified an unexpected complexity of functional conservation and divergence. Under well-fed conditions, ascaroside biosynthesis proceeds exclusively via Ppa daf-22.1 In contrast, starvation conditions induce Ppa-daf-22.2 activity, resulting in the production of a specific subset of ascarosides. Gene expression studies indicate a reciprocal up-regulation of both Ppa-daf-22 genes, which is, however, independent of starvation. Thus, our study reveals an unexpected functional complexity of dauer development and evolution. PMID- 27189573 TI - Phylodynamics with Migration: A Computational Framework to Quantify Population Structure from Genomic Data. AB - When viruses spread, outbreaks can be spawned in previously unaffected regions. Depending on the time and mode of introduction, each regional outbreak can have its own epidemic dynamics. The migration and phylodynamic processes are often intertwined and need to be taken into account when analyzing temporally and spatially structured virus data. In this article, we present a fully probabilistic approach for the joint reconstruction of phylodynamic history in structured populations (such as geographic structure) based on a multitype birth death process. This approach can be used to quantify the spread of a pathogen in a structured population. Changes in epidemic dynamics through time within subpopulations are incorporated through piecewise constant changes in transmission parameters.We analyze a global human influenza H3N2 virus data set from a geographically structured host population to demonstrate how seasonal dynamics can be inferred simultaneously with the phylogeny and migration process. Our results suggest that the main migration path among the northern, tropical, and southern region represented in the sample analyzed here is the one leading from the tropics to the northern region. Furthermore, the time-dependent transmission dynamics between and within two HIV risk groups, heterosexuals and injecting drug users, in the Latvian HIV epidemic are investigated. Our analyses confirm that the Latvian HIV epidemic peaking around 2001 was mainly driven by the injecting drug user risk group. PMID- 27189576 TI - Editorial. PMID- 27189575 TI - Long-term expression of miRNA for RNA interference using a novel vector system based on a negative-strand RNA virus. AB - RNA interference (RNAi) has emerged as a promising technique for gene therapy. However, the safe and long-term expression of small RNA molecules is a major concern for the application of RNAi therapies in vivo. Borna disease virus (BDV), a non-segmented, negative-strand RNA virus, establishes a persistent infection without obvious cytopathic effects. Unique among animal non-retroviral RNA viruses, BDV persistently establishes a long-lasting persistent infection in the nucleus. These features make BDV ideal for RNA virus vector persistently expressing small RNAs. Here, we demonstrated that the recombinant BDV (rBDV) containing the miR-155 precursor, rBDV-miR-155, persistently expressed miR-155 and efficiently silenced its target gene. The stem region of the miR-155 precursor in rBDV-miR-155 was replaceable by any miRNA sequences of interest and that such rBDVs efficiently silence the expression of target genes. Collectively, BDV vector would be a novel RNA virus vector enabling the long-term expression of miRNAs for RNAi therapies. PMID- 27189577 TI - Cytotoxic T cells go awry in inclusion body myositis. PMID- 27189574 TI - Macrophage ABHD5 promotes colorectal cancer growth by suppressing spermidine production by SRM. AB - Metabolic reprogramming in stromal cells plays an essential role in regulating tumour growth. The metabolic activities of tumour-associated macrophages (TAMs) in colorectal cancer (CRC) are incompletely characterized. Here, we identify TAM derived factors and their roles in the development of CRC. We demonstrate that ABHD5, a lipolytic co-activator, is ectopically expressed in CRC-associated macrophages. We demonstrate in vitro and in mouse models that macrophage ABHD5 potentiates growth of CRC cells. Mechanistically, ABHD5 suppresses spermidine synthase (SRM)-dependent spermidine production in macrophages by inhibiting the reactive oxygen species-dependent expression of C/EBPE, which activates transcription of the srm gene. Notably, macrophage-specific ABHD5 transgene induced CRC growth in mice can be prevented by an additional SRM transgene in macrophages. Altogether, our results show that the lipolytic factor ABHD5 suppresses SRM-dependent spermidine production in TAMs and potentiates the growth of CRC. The ABHD5/SRM/spermidine axis in TAMs might represent a potential target for therapy. PMID- 27189578 TI - Cerebellum in Alzheimer's disease and frontotemporal dementia: not a silent bystander. PMID- 27189579 TI - Monitoring the progression of Alzheimer's disease with tau-PET. PMID- 27189580 TI - Distinct tau PET imaging patterns in typical and atypical Alzheimer's disease. PMID- 27189582 TI - Corrigendum. PMID- 27189583 TI - Prevalence estimation of tick-borne encephalitis virus (TBEV) antibodies in dogs from Finland using novel dog anti-TBEV IgG MAb-capture and IgG immunofluorescence assays based on recombinant TBEV subviral particles. AB - Tick-borne encephalitis (TBE) is one of the most dangerous human neurological infections occurring in Europe and Northern parts of Asia with thousands of cases and millions vaccinated against it. The risk of TBE might be assessed through analyses of the samples taken from wildlife or from animals which are in close contact with humans. Dogs have been shown to be a good sentinel species for these studies. Serological assays for diagnosis of TBE in dogs are mainly based on purified and inactivated TBEV antigens. Here we describe novel dog anti-TBEV IgG monoclonal antibody (MAb)-capture assay which is based on TBEV prME subviral particles expressed in mammalian cells from Semliki Forest virus (SFV) replicon as well as IgG immunofluorescence assay (IFA) which is based on Vero E6 cells transfected with the same SFV replicon. We further demonstrate their use in a small-scale TBEV seroprevalence study of dogs representing different regions of Finland. Altogether, 148 dog serum samples were tested by novel assays and results were compared to those obtained with a commercial IgG enzyme immunoassay (EIA), hemagglutination inhibition test and IgG IFA with TBEV infected cells. Compared to reference tests, the sensitivities of the developed assays were 90 100% and the specificities of the two assays were 100%. Analysis of the dog serum samples showed a seroprevalence of 40% on Aland Islands and 6% on Southwestern archipelago of Finland. In conclusion, a specific and sensitive EIA and IFA for the detection of IgG antibodies in canine sera were developed. Based on these assays the seroprevalence of IgG antibodies in dogs from different regions of Finland was assessed and was shown to parallel the known human disease burden as the Southwestern archipelago and Aland Islands in particular had considerable dog TBEV antibody prevalence and represent areas with high risk of TBE for humans. PMID- 27189584 TI - Tick-borne encephalitis-still on the map: Report of the 18th annual meeting of the international scientific working group on tick-borne encephalitis (ISW-TBE). AB - The 18th meeting of the International Scientific Working Group on Tick-Borne Encephalitis (ISW-TBE)-a group of neurologists, general practitioners, clinicians, travel physicians, virologists, pediatricians and epidemiologists-was held under the title 'Tick-borne encephalitis-still on the map'. The conference agenda was divided into six sessions: 'National Implementation of EU notifiable disease status', 'Virology', 'Epidemiology and Risk areas & Poster Walk Epidemiological Update', 'Clinic', 'Environmental Factors' and 'New Findings and Diagnosis'. Key topics such as 'TBE as a notifiable disease-results of the third European survey', 'TBE vaccines over the years', 'Overview of flaviviruses', 'TBE virus phylogenetics', 'Current epidemiological developments and investigations', 'Clinical aspects', 'TBE in veterinary medicine', 'Laboratory diagnostic', 'Occupational risk', 'Allergy, obesity, and vaccination' were presented and extensively discussed. PMID- 27189585 TI - Celebrating variability and a call to limit systematisation: the example of the Behaviour Change Technique Taxonomy and the Behaviour Change Wheel. AB - Within any discipline there is always a degree of variability. For medicine it takes the form of Health Professional's behaviour, for education it's the style and content of the classroom, and for health psychology, it can be found in patient's behaviour, the theories used and clinical practice. Over recent years, attempts have been made to reduce this variability through the use of the Behaviour Change Technique Taxonomy, the COM-B and the Behaviour Change Wheel. This paper argues that although the call for better descriptions of what is done is useful for clarity and replication, this systematisation may be neither feasible nor desirable. In particular, it is suggested that the gaps inherent in the translational process from coding a protocol to behaviour will limit the effectiveness of reducing patient variability, that theory variability is necessary for the health and well-being of a discipline and that practice variability is central to the professional status of our practitioners. It is therefore argued that we should celebrate rather than remove this variability in order for our discipline to thrive and for us to remain as professionals rather than as technicians. PMID- 27189586 TI - Targeting membrane proteins for antibody discovery using phage display. AB - A critical factor in the successful isolation of new antibodies by phage display is the presentation of a correctly folded antigen. While this is relatively simple for soluble proteins which can be purified and immobilized onto a plastic surface, membrane proteins offer significant challenges for antibody discovery. Whole cell panning allows presentation of the membrane protein in its native conformation, but is complicated by a low target antigen density, high background of irrelevant antigens and non-specific binding of phage particles to cell surfaces. The method described here uses transient transfection of alternating host cell lines and stringent washing steps to address each of these limitations. The successful isolation of antibodies from a naive scFv library is described for three membrane bound proteins; human CD83, canine CD117 and bat CD11b. PMID- 27189581 TI - Activational and effort-related aspects of motivation: neural mechanisms and implications for psychopathology. AB - Motivation has been defined as the process that allows organisms to regulate their internal and external environment, and control the probability, proximity and availability of stimuli. As such, motivation is a complex process that is critical for survival, which involves multiple behavioural functions mediated by a number of interacting neural circuits. Classical theories of motivation suggest that there are both directional and activational aspects of motivation, and activational aspects (i.e. speed and vigour of both the instigation and persistence of behaviour) are critical for enabling organisms to overcome work related obstacles or constraints that separate them from significant stimuli. The present review discusses the role of brain dopamine and related circuits in behavioural activation, exertion of effort in instrumental behaviour, and effort related decision-making, based upon both animal and human studies. Impairments in behavioural activation and effort-related aspects of motivation are associated with psychiatric symptoms such as anergia, fatigue, lassitude and psychomotor retardation, which cross multiple pathologies, including depression, schizophrenia, and Parkinson's disease. Therefore, this review also attempts to provide an interdisciplinary approach that integrates findings from basic behavioural neuroscience, behavioural economics, clinical neuropsychology, psychiatry, and neurology, to provide a coherent framework for future research and theory in this critical field. Although dopamine systems are a critical part of the brain circuitry regulating behavioural activation, exertion of effort, and effort-related decision-making, mesolimbic dopamine is only one part of a distributed circuitry that includes multiple neurotransmitters and brain areas. Overall, there is a striking similarity between the brain areas involved in behavioural activation and effort-related processes in rodents and in humans. Animal models of effort-related decision-making are highly translatable to humans, and an emerging body of evidence indicates that alterations in effort based decision-making are evident in several psychiatric and neurological disorders. People with major depression, schizophrenia, and Parkinson's disease show evidence of decision-making biases towards a lower exertion of effort. Translational studies linking research with animal models, human volunteers, and clinical populations are greatly expanding our knowledge about the neural basis of effort-related motivational dysfunction, and it is hoped that this research will ultimately lead to improved treatment for motivational and psychomotor symptoms in psychiatry and neurology. PMID- 27189588 TI - Does monosodium glutamate really cause headache? : a systematic review of human studies. AB - Although monosodium glutamate (MSG) is classified as a causative substance of headache in the International Classification of Headache Disorders 3rd edition (ICHD-III beta), there is no literature in which causal relationship between MSG and headache was comprehensively reviewed. We performed systematic review of human studies which include the incidence of headache after an oral administration of MSG. An analysis was made by separating the human studies with MSG administration with or without food, because of the significant difference of kinetics of glutamate between those conditions (Am J Clin Nutr 37:194-200, 1983; J Nutr 130:1002S-1004S, 2000) and there are some papers which report the difference of the manifestation of symptoms after MSG ingestion with or without food (Food Chem Toxicol 31:1019-1035, 1993; J Nutr 125:2891S-2906S, 1995). Of five papers including six studies with food, none showed a significant difference in the incidence of headache except for the female group in one study. Of five papers including seven studies without food, four studies showed a significant difference. Many of the studies involved administration of MSG in solution at high concentrations (>2 %). Since the distinctive MSG is readily identified at such concentrations, these studies were thought not to be properly blinded. Because of the absence of proper blinding, and the inconsistency of the findings, we conclude that further studies are required to evaluate whether or not a causal relationship exists between MSG ingestion and headache. PMID- 27189587 TI - Endovanilloids are potential activators of the trigeminovascular nocisensor complex. AB - BACKGROUND: In the dura mater encephali a significant population of trigeminal afferents coexpress the nociceptive ion channel transient receptor potential vanilloid type 1 (TRPV1) receptor and calcitonin gene-related peptide (CGRP). Release of CGRP serves the central transmission of sensory information, initiates local tissue reactions and may also sensitize the nociceptive pathway. To reveal the possible activation of meningeal TRPV1 receptors by endogenously synthetized agonists, the effects of arachidonylethanolamide (anandamide) and N-arachidonoyl dopamine (NADA) were studied on dural vascular reactions and meningeal CGRP release. METHODS: Changes in meningeal blood flow were measured with laser Doppler flowmetry in a rat open cranial window preparation following local dural applications of anandamide and NADA. The release of CGRP evoked by endovanilloids was measured with ELISA in an in vitro dura mater preparation. RESULTS: Topical application of NADA induced a significant dose-dependent increase in meningeal blood flow that was markedly inhibited by pretreatments with the TRPV1 antagonist capsazepine, the CGRP antagonist CGRP8-37, or by prior systemic capsaicin desensitization. Administration of anandamide resulted in minor increases in meningeal blood flow that was turned into vasoconstriction at the higher concentration. In the in vitro dura mater preparation NADA evoked a significant increase in CGRP release. Cannabinoid CB1 receptors of CGRP releasing nerve fibers seem to counteract the TRPV1 agonistic effect of anandamide in a dose dependent fashion, a result which is confirmed by the facilitating effect of CB1 receptor inhibition on CGRP release and its reversing effect on the blood flow. CONCLUSIONS: The present findings demonstrate that endovanilloids are potential activators of meningeal TRPV1 receptors and, consequently the trigeminovascular nocisensor complex that may play a significant role in the pathophysiology of headaches. The results also suggest that prejunctional CB1 receptors may modulate meningeal vascular responses. PMID- 27189590 TI - The assignment of the configuration for alpha-hydroxy acid esters using a CEC strategy. AB - A simple and efficient (1)H NMR method for determining the absolute configuration of chiral alpha-hydroxy acid esters using a competing enantioselective conversion (CEC) strategy was developed. The alpha-hydroxy acid esters were acylated in the presence of Feng's chiral N,N'-dioxide-scandium(iii) complex, and the faster reaction was identified when one enantiomer of the chiral alpha-hydroxy acid ester was treated with both enantiomers of the ligand by NMR analysis of the reaction mixture without further purification. A mnemonic is presented to aid the assignment of the absolute configuration of the substrates. PMID- 27189589 TI - Don't worry; be informed about the epigenetics of anxiety. AB - Epigenetic processes regulate gene expression independent of the DNA sequence and are increasingly being investigated as contributors to the development of behavioral disorders. Environmental insults, such as stress, diet, or toxin exposure, can affect epigenetic mechanisms, including chromatin remodeling, DNA methylation, and non-coding RNAs that, in turn, alter the organism's phenotype. In this review, we examine the literature, derived at both the preclinical (animal) and clinical (human) levels, on epigenetic alterations associated with anxiety disorders. Using animal models of anxiety, researchers have identified epigenetic changes in several limbic and cortical brain regions known to be involved in stress and emotion responses. Environmental manipulations have been imposed prior to conception, during prenatal or early postnatal periods, and at juvenile and adult ages. Time of perturbation differentially affects the epigenome and many changes are brain region-specific. Although some sex-dependent effects are reported in animal studies, more research employing both sexes is needed particularly given that females exhibit a disproportionate number of anxiety disorders. The human literature is in its infancy but does reveal some epigenetic associations with anxiety behaviors and disorders. In particular, effects in monoaminergic systems are seen in line with evidence from etiological and treatment research. Further, there is evidence that epigenetic changes may be inherited to affect subsequent generations. We speculate on how epigenetic processes may interact with genetic contributions to inform prevention and treatment strategies for those who are at risk for or have anxiety disorders. PMID- 27189591 TI - Effects of age and sex on neuromuscular-mechanical determinants of muscle strength. AB - The aim of this study was to concurrently assess the effect of age on neuromuscular and mechanical properties in 24 young (23.6 +/- 3.7 years) and 20 older (66.5 +/- 3.8 years) healthy males and females. Maximal strength of knee extensors (KE) and flexors (KF), contractile rate of torque development (RTD) and neural activation of agonist-antagonist muscles (surface EMG) were examined during maximal voluntary isometric contraction (MVIC). Tissue stiffness (i.e. musculo-articular stiffness (MAS) and muscle stiffness (MS)) was examined via the free-oscillation technique, whereas muscle architecture (MA) of the vastus lateralis and subcutaneous fat were measured by ultrasonography. Males exhibited a greater age-related decline for KE (47.4 %) and KF (53.1 %) MVIC, and RTD (60.4 %) when compared to females (32.9, 42.6 and 34.0 %, respectively). Neural activation of agonist muscles during KE MVIC falls markedly with ageing; however, no age and sex effects were observed in the antagonist co-activation. MAS and MS were lower in elderly compared with young participants and in females compared with males. Regarding MA, main effects for age (young 23.0 +/- 3.3 vs older 19.5 +/- 2.0 mm) and sex (males 22.4 +/- 3.5 vs females 20.4 +/- 2.7 mm) were detected in muscle thickness. For fascicle length, there was an effect of age (young 104.6 +/- 8.8 vs older 89.8 +/- 10.5 mm), while for pennation angle, there was an effect of sex (males 13.3 +/- 2.4 vs females 11.5 +/- 1.7 degrees ). These findings suggest that both neuromuscular and mechanical declines are important contributors to the age-related loss of muscle strength/function but with some peculiar sex-related differences. PMID- 27189592 TI - Evaluation and comparison of a flumethrin-imidacloprid collar and repeated monthly treatments of fipronil/(s)-methoprene to control flea, Ctenocephalides f. felis, infestations on cats for eight months. AB - BACKGROUND: This controlled laboratory study was designed to evaluate the efficacy of the 10 % imidacloprid/4.5 % flumethrin collar (Seresto(r), Bayer Animal Health) against fleas (Ctenocephalides f. felis) on cats, when compared to fipronil (9.8 %w/w)/(s)-methoprene (11.8 % w/w) topical spot-on formulation (Frontline(r) Plus for Cats and Kittens, Merial). METHODS: Thirty cats were randomized into three groups of ten animals based on pre-treatment flea counts: Group 1: imidacloprid/flumethrin collar; Group 2: fipronil/(s)-methoprene topical spot-on and Group 3: non-treated controls. The imidacloprid/flumethrin collars were applied one time on Day 0, while the fipronil/(s)-methoprene spot-on was administered every 30 days from Day 0 through Day 210. Cats were infested with 100 fleas on study days 0, 7, 14, 29, 59, 89, 119, 149, 179, 209 and 239. All flea counts were conducted by combing to remove fleas on post-treatment days 2, 8, 15, 30, 60, 90, 120, 150, 180, 210 and 240. RESULTS: The efficacy of the imidacloprid/flumethrin collar ranged from 98.2 to 100 % for eight months. The efficacy of fipronil/(s)-methoprene spot-on ranged from 68.2 to 99.9 %. Efficacy was < 85 % for fipronil/(s)-methoprene on Days 90, 150 and 210. The flea counts in both treatment groups were significantly fewer than those in the non-treated control group at every post-treatment study day (P < 0.0001). In addition, there were significantly fewer fleas in the imidacloprid/flumethrin collar group when compared to the fipronil/(s)-methoprene group on Days 90, 150 and 210 (P < 0.0001). CONCLUSIONS: This study demonstrated that the imidacloprid/flumethrin collar (Seresto(r), Bayer Animal Health) maintained excellent ( > 98.2 %) efficacy against fleas on cats for the entire 8 month study. Monthly applications of fipronil/(s)-methoprene (Frontline(r) Plus for Cats and Kittens, Merial) generally had high, but variable (68.2 to 99.9 %) efficacy over the course of the eight month study. Based on the very high residual efficacy achieved by the imidacloprid/flumethrin collar in this study, veterinarians should expect that this collar will control and eliminate existing flea infestations on cats and in their in-home premises as long as every flea infested host is treated. PMID- 27189594 TI - Bisphenol A in Hemodialysis Patient: An Open Question. PMID- 27189593 TI - Risk of Liver Injury Associated with Green Tea Extract in SLIMQUICK((r)) Weight Loss Products: Results from the DILIN Prospective Study. AB - INTRODUCTION: Herbal and dietary supplements (HDS) have been increasingly recognized as a cause for acute liver injury (Navarro et al. Hepatology 60(4):1399-1408, 2014; Bailey et al. J Nutr 141:261-266, 2011). HDS products frequently contain numerous ingredients, and are marketed under various product names. A perusal of marketed weight loss products indicates that green tea extract (GTE) is a common ingredient in many. We aimed to describe the course and outcome of six patients who developed liver injury attributed to SLIMQUICK((r)) weight loss products. METHODS: Patients with suspected drug-induced liver injury were enrolled in a prospective study of the Drug-Induced Liver Injury Network (DILIN) and causality was assessed by a panel of hepatologists. During the period under study, 6 of 1091 cases of liver injury were attributed to a SLIMQUICK((r)) product and were assigned causality scores of probable, highly likely, or definite. RESULTS: Six cases of acute liver injury attributed to SLIMQUICK((r)) products were enrolled in the DILIN prospective study between 2007 and 2011. All were women aged 22 to 58 years. Two had a normal body weight and four were mildly obese (body mass index 22.9-32.2 kg/m(2)). All were taking SLIMQUICK((r)) products for weight loss and no patient reported prior use. Laboratory tests revealed a hepatocellular pattern of injury, with initial alanine aminotransferase (ALT) levels above 1000 U/L in all but one patient. Three patients were hospitalized and one underwent successful liver transplantation. No patients died of liver injury. GTE and/or its component catechins were listed among the ingredients for five of the six products. CONCLUSIONS: SLIMQUICK((r)) products can lead to severe acute hepatocellular liver injury, which may result in transplantation. Given the frequency of GTE as a component in weight loss products, this ingredient should be studied further as a possible cause for liver injury. PMID- 27189596 TI - Pyrococcus kukulkanii sp. nov., a hyperthermophilic, piezophilic archaeon isolated from a deep-sea hydrothermal vent. AB - A novel hyperthermophilic, piezophilic, anaerobic archaeon, designated NCB100T, was isolated from a hydrothermal vent flange fragment collected in the Guaymas basin at the hydrothermal vent site named 'Rebecca's Roost' at a depth of 1997 m. Enrichment and isolation were performed at 100 degrees C under atmospheric pressure. Cells of strain NCB100T were highly motile, irregular cocci with a diameter of ~1 um. Growth was recorded at temperatures between 70 and 112 degrees C (optimum 105 degrees C) and hydrostatic pressures of 0.1-80 MPa (optimum 40-50 MPa). Growth was observed at pH 3.5-8.5 (optimum pH 7) and with 1.5-7 % NaCl (optimum at 2.5-3 %). Strain NCB100T was a strictly anaerobic chemo organoheterotroph and grew on complex proteinaceous substrates such as yeast extract, peptone and tryptone, as well as on glycogen and starch. Elemental sulfur was required for growth and was reduced to hydrogen sulfide. The fermentation products from complex proteinaceous substrates were CO2 and H2. The G+C content of the genomic DNA was 41.3 %. Phylogenetic analysis of the 16S rRNA gene sequence revealed that strain NCB100T belongs to the genus Pyrococcus, showing 99 % similarity with the other described species of the genus Pyrococcus. On the basis of physiological characteristics, DNA G+C content, similarity level between ribosomal proteins and an average nucleotide identity value of 79 %, strain NCB100T represents a novel species for which the name Pyrococcus kukulkanii sp. nov. is proposed. The type strain is NCB100T (=DSM 101590T=Souchotheque de Bretagne BG1337T). PMID- 27189597 TI - Treatment of gynecological disease in obese patient: which role for telelap ALF-X platform? PMID- 27189595 TI - The Breathing for Life Trial: a randomised controlled trial of fractional exhaled nitric oxide (FENO)-based management of asthma during pregnancy and its impact on perinatal outcomes and infant and childhood respiratory health. AB - BACKGROUND: Asthma exacerbations are common during pregnancy and associated with an increased risk of adverse perinatal outcomes. Adjusting asthma treatment based on airway inflammation rather than symptoms reduces the exacerbation rate by 50 %. The Breathing for Life Trial (BLT) will test whether this approach also improves perinatal outcomes. METHODS/DESIGN: BLT is a multicentre, parallel group, randomised controlled trial of asthma management guided by fractional exhaled nitric oxide (FENO, a marker of eosinophilic airway inflammation) compared to usual care, with prospective infant follow-up. Women with physician diagnosed asthma, asthma symptoms and/or medication use in the previous 12 months, who are 12-22 weeks gestation, will be eligible for inclusion. Women randomised to the control group will have one clinical assessment of their asthma, including self-management education. Any treatment changes will be made by their general practitioner. Women randomised to the intervention group will have clinical assessments every 3-6 weeks during pregnancy, and asthma treatments will be adjusted every second visit based on an algorithm which uses FENO to adjust inhaled corticosteroid (ICS) dose (increase in dose when FENO >29 parts per billion (ppb), decrease in dose when FENO <19 ppb, and no change when FENO is between 19 and 29 ppb). A long acting beta agonist (LABA) will be added when symptoms remain uncontrolled. Both the control and intervention groups will report on exacerbations at a postpartum phone interview. The primary outcome is adverse perinatal outcome (a composite measure including preterm birth, intrauterine growth restriction, neonatal hospitalisation at birth or perinatal mortality), assessed from hospital records. Secondary outcomes will be each component of the primary outcome, maternal exacerbations requiring medical intervention during pregnancy (both smokers and non-smokers), and hospitalisation and emergency department presentation for wheeze, bronchiolitis or croup in the first 12 months of infancy. Outcome assessment and statistical analysis of the primary outcome will be blinded. To detect a reduction in adverse perinatal outcomes from 35 % to 26 %, 600 pregnant women with asthma per group are required. DISCUSSION: This trial will provide evidence for the effectiveness of a FENO-based management strategy in improving perinatal outcomes in pregnant women with asthma. If successful, this would improve the management of pregnant women with asthma worldwide. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12613000202763 . PMID- 27189598 TI - Therapeutic Approaches Targeting Pathological Tau Aggregates. AB - Neurodegenerative diseases characterized by the accumulation of tau aggregates are increasing in prevalence to epidemic-like levels and there is currently no effective treatment. For many years, the focus of tau-based research was on the fibrillar, neurofibrillary tangles. However, the compilation of evidence obtained from numerous laboratories in the past few years suggests that soluble intermediate aggregates-tau oligomers-are actually the most toxic protein species in disease. Thus, therapeutic agents that target oligomeric tau specifically may be the most effective routes for treatment. A great deal of progress has been made in the pre-clinical evaluation of a number of different anti-tau therapeutics. Upstream modulators of tau modifications have been evaluated and may provide some benefits, but likely will not be capable of eliminating toxic tau entirely. Protein chaperones capable of modulating the structure of tau and targeting it for degradation are another field of study, however, the broad effects of chaperones make side effects a concern. Thus, more specific agents capable of eliminating the most toxic species in disease are promising. Small molecules designed to inhibit aggregation, as well as immunotherapy with antibodies specific for toxic tau aggregates present the most advancement as potential treatments. The concerted effort across a number of groups to investigate potential mechanisms to inhibit tau toxicity represents great progress in the field and provides hope that effective treatments will be discovered. PMID- 27189599 TI - Non-Demented Individuals with Alzheimer's Disease Neuropathology: Resistance to Cognitive Decline May Reveal New Treatment Strategies. AB - Alzheimer's disease (AD) is a terminal neurodegenerative disorder that is characterized by accumulation of amyloid plaques and neurofibrillary tangles in the central nervous system. However, certain individuals remain cognitively intact despite manifestation of substantial plaques and tangles consistent with what would be normally associated with fully symptomatic AD. Mechanisms that allow these subjects to escape dementia remain unresolved and understanding such protective biological processes could reveal novel targets for the development of effective treatments for AD. In this review article we discuss potential compensatory mechanisms that allow these individuals to remain cognitively intact despite the typical AD neuropathology. PMID- 27189601 TI - Heterocyclic Scaffolds for the Treatment of Alzheimer's Disease. AB - BACKGROUND: The treatment and diagnosis of Alzheimer's Disease (AD) are two of the most urgent goals for research around the world. The cognitive decline is generally associated with the elevated levels of extracellular senile plaques, intracellular neurofibrillary tangles (NFTs), and with a progressive shutdown of the cholinergic basal forebrain neurons transmission. Even if several key targets are under fervent investigation in the cure of AD, till now, the only approved therapeutic strategy is the treatment of symptoms by using cholinesterases inhibitors. It has been demonstrated that both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes are not only responsible of acetylcholine levels, but also play an pivotal role in Abeta-aggregation during the early stages of senile plaque formation. On the other hand the difficult management of AD is also related to effective diagnostic methods and efficient assays for the study of pathological features. In such complex a wide framework, heterocyclic molecules are essential backbone to build new and selective drugs as well as diagnostic probes. METHODS: The goal of this review is to examine a selected sample of relevant applications of five- and six-membered heterocycles in AD's therapeutic approaches. RESULTS: Concerning the research on AD, the contribution of heterocyclic compounds is huge and here we report some representative examples. The review is organized in two main sections focused on five and six membered heterocycles. The analyzed cases have been classified on the base of the structural features of molecules, taking into account the progressive increase in heteroatoms number. CONCLUSION: The discovery of an effective therapy or a diagnostic protocol for AD is still far, but consistent improvements are underway and contribution of heterocyclic compounds will be consistent and hopefully determinant. PMID- 27189602 TI - Alzheimer's Disease and Molecular Chaperones: Current Knowledge and the Future of Chaperonotherapy. AB - BACKGROUND: Alzheimer's disease (AD) is a dementia, a neurodegenerative condition, and a protein-misfolding disease or proteinopathy, characterized by protein deposits, extracellular plaques and intracellular neurofibrillary tangles, which contain the AD's typical pathological proteins, abnormal beta amyloid and hyperphosphorylated tau, respectively, and are located predominantly in the cortex of the frontal, parietal, and temporal brain lobes. What is the role of molecular chaperones in AD? Data indicate that molecular chaperones, also known as Hsp, are involved in AD, probably displaying protective roles and/or acting as pathogenic factors as it occurs in chaperonopathies in which case AD would be suitable to chaperonotherapy. Hsp60, Hsp70, and Hsp90 can be augmented and overexpressed or diminished and downregulated in various situations in AD affected tissues and cells, indicating they are active during disease development and progression. QUESTION: What is the role of molecular chaperones in AD? Data indicate that molecular chaperones, also known as Hsp, are involved in AD, probably displaying protective roles and/or acting as pathogenic factors as it occurs in chaperonopathies in which case AD would be suitable to chaperonotherapy. OBJECTIVE: Investigate the role of Hsp in AD, focusing on Hsp60, Hsp70, and Hsp90. METHOD: Critical examination of published data. RESULTS: Hsp60, Hsp70, and Hsp90 can be augmented and overexpressed or diminished and downregulated in various situations in AD affected tissues and cells, indicating they are active during disease development and progression. CONCLUSION AND PERSPECTIVES: Notwithstanding that the roles and mechanisms of action of chaperones in AD are still incompletely understood, there is already enough evidence to encourage the development of therapeutic strategies targeting them, either to block their activity in case they promote disease progression or to boost their performance when they are protective. The latter is an example of positive chaperonotherapy, which also includes chaperone replacement via gene or protein administration. On the contrary, if a chaperone is found to help the disease, it has to be blocked or eliminated, which constitute modalities of negative chaperonotherapy. PMID- 27189603 TI - Gender Differences in Autonomic Control of the Cardiovascular System. AB - BACKGROUND: The autonomic nervous system (ANS) is a key regulator of the cardiovascular system. The two arms of the ANS, sympathetic and parasympathetic (vagal) have co-regulatory effects on cardiac homeostasis. ANS modulation and dysfunction are also believed to affect various cardiac disease states. Over the past decade, there has been increasing evidence suggesting gender differences in ANS activity. METHODS: In multiple previous studies, ANS activity was primarily assessed using heart rate variability, muscle sympathetic nerve activity, coronary blood flow velocity, and plasma biomarkers. Heart rate variability is a non-invasive measure, which can be analyzed in terms of low frequency and high frequency oscillations, which indicate the sympathetic and parasympathetic tone, respectively. These measures have been studied between women and men in states of rest and stress, and in cardiac disease. CONCLUSION: Studies support the concept of a significant gender difference in ANS activity. Further studies are indicated to elucidate specific differences and mechanisms, which could guide targeted therapy of various cardiovascular disease states. PMID- 27189605 TI - Erratum to: A retrospective analysis of nonresponse to daily teriparatide treatment. PMID- 27189606 TI - PolyQ 2.0: an improved version of PolyQ, a database of human polyglutamine proteins. PMID- 27189604 TI - Room temperature housing results in premature cancellous bone loss in growing female mice: implications for the mouse as a preclinical model for age-related bone loss. AB - Room temperature housing (22 degrees C) results in premature cancellous bone loss in female mice. The bone loss was prevented by housing mice at thermoneutral temperature (32 degrees C). Thermogenesis differs markedly between mice and humans and mild cold stress induced by standard room temperature housing may introduce an unrecognized confounding variable into preclinical studies. INTRODUCTION: Female mice are often used as preclinical models for osteoporosis but, in contrast to humans, mice exhibit cancellous bone loss during growth. Mice are routinely housed at room temperature (18-23 degrees C), a strategy that exaggerates physiological differences in thermoregulation between mice (obligatory daily heterotherms) and humans (homeotherms). The purpose of this investigation was to assess whether housing female mice at thermoneutral (temperature range where the basal rate of energy production is at equilibrium with heat loss) alters bone growth, turnover and microarchitecture. METHODS: Growing (4-week-old) female C57BL/6J and C3H/HeJ mice were housed at either 22 or 32 degrees C for up to 18 weeks. RESULTS: C57BL/6J mice housed at 22 degrees C experienced a 62 % cancellous bone loss from the distal femur metaphysis during the interval from 8 to 18 weeks of age and lesser bone loss from the distal femur epiphysis, whereas cancellous and cortical bone mass in 32 degrees C-housed mice were unchanged or increased. The impact of thermoneutral housing on cancellous bone was not limited to C57BL/6J mice as C3H/HeJ mice exhibited a similar skeletal response. The beneficial effects of thermoneutral housing on cancellous bone were associated with decreased Ucp1 gene expression in brown adipose tissue, increased bone marrow adiposity, higher rates of bone formation, higher expression levels of osteogenic genes and locally decreased bone resorption. CONCLUSIONS: Housing female mice at 22 degrees C resulted in premature cancellous bone loss. Failure to account for species differences in thermoregulation may seriously confound interpretation of studies utilizing mice as preclinical models for osteoporosis. PMID- 27189600 TI - AFM-Based Single Molecule Techniques: Unraveling the Amyloid Pathogenic Species. AB - BACKGROUND: A wide class of human diseases and neurodegenerative disorders, such as Alzheimer's disease, is due to the failure of a specific peptide or protein to keep its native functional conformational state and to undergo a conformational change into a misfolded state, triggering the formation of fibrillar cross-beta sheet amyloid aggregates. During the fibrillization, several coexisting species are formed, giving rise to a highly heterogeneous mixture. Despite its fundamental role in biological function and malfunction, the mechanism of protein self-assembly and the fundamental origins of the connection between aggregation, cellular toxicity and the biochemistry of neurodegeneration remains challenging to elucidate in molecular detail. In particular, the nature of the specific state of proteins that is most prone to cause cytotoxicity is not established. METHODS: In the present review, we present the latest advances obtained by Atomic Force Microscopy (AFM) based techniques to unravel the biophysical properties of amyloid aggregates at the nanoscale. Unraveling amyloid single species biophysical properties still represents a formidable experimental challenge, mainly because of their nanoscale dimensions and heterogeneous nature. Bulk techniques, such as circular dichroism or infrared spectroscopy, are not able to characterize the heterogeneity and inner properties of amyloid aggregates at the single species level, preventing a profound investigation of the correlation between the biophysical properties and toxicity of the individual species. CONCLUSION: The information delivered by AFM based techniques could be central to study the aggregation pathway of proteins and to design molecules that could interfere with amyloid aggregation delaying the onset of misfolding diseases. PMID- 27189607 TI - Argo: enabling the development of bespoke workflows and services for disease annotation. AB - Argo (http://argo.nactem.ac.uk) is a generic text mining workbench that can cater to a variety of use cases, including the semi-automatic annotation of literature. It enables its technical users to build their own customised text mining solutions by providing a wide array of interoperable and configurable elementary components that can be seamlessly integrated into processing workflows. With Argo's graphical annotation interface, domain experts can then make use of the workflows' automatically generated output to curate information of interest.With the continuously rising need to understand the aetiology of diseases as well as the demand for their informed diagnosis and personalised treatment, the curation of disease-relevant information from medical and clinical documents has become an indispensable scientific activity. In the Fifth BioCreative Challenge Evaluation Workshop (BioCreative V), there was substantial interest in the mining of literature for disease-relevant information. Apart from a panel discussion focussed on disease annotations, the chemical-disease relations (CDR) track was also organised to foster the sharing and advancement of disease annotation tools and resources.This article presents the application of Argo's capabilities to the literature-based annotation of diseases. As part of our participation in BioCreative V's User Interactive Track (IAT), we demonstrated and evaluated Argo's suitability to the semi-automatic curation of chronic obstructive pulmonary disease (COPD) phenotypes. Furthermore, the workbench facilitated the development of some of the CDR track's top-performing web services for normalising disease mentions against the Medical Subject Headings (MeSH) database. In this work, we highlight Argo's support for developing various types of bespoke workflows ranging from ones which enabled us to easily incorporate information from various databases, to those which train and apply machine learning-based concept recognition models, through to user-interactive ones which allow human curators to manually provide their corrections to automatically generated annotations. Our participation in the BioCreative V challenges shows Argo's potential as an enabling technology for curating disease and phenotypic information from literature.Database URL: http://argo.nactem.ac.uk. PMID- 27189608 TI - A web resource for mining HLA associations with adverse drug reactions: HLA-ADR. AB - Human leukocyte antigens (HLA) are an important family of genes involved in the immune system. Their primary function is to allow the host immune system to be able to distinguish between self and non-self peptides-e.g. derived from invading pathogens. However, these genes have also been implicated in immune-mediated adverse drug reactions (ADRs), presenting a problem to patients, clinicians and pharmaceutical companies. We have previously developed the Allele Frequency Net Database (AFND) that captures the allelic and haplotype frequencies for these HLA genes across many healthy populations from around the world. Here, we report the development and release of the HLA-ADR database that captures data from publications where HLA alleles and haplotypes have been associated with ADRs (e.g. Stevens-Johnson Syndrome/toxic epidermal necrolysis and drug-induced liver injury). HLA-ADR was created by using data obtained through systematic review of the literature and semi-automated literature mining. The database also draws on data already present in AFND allowing users to compare and analyze allele frequencies in both ADR patients and healthy populations. The HLA-ADR database provides clinicians and researchers with a centralized resource from which to investigate immune-mediated ADRs.Database URL: http://www.allelefrequencies.net/hla-adr/. PMID- 27189609 TI - A knowledge-poor approach to chemical-disease relation extraction. AB - The article describes a knowledge-poor approach to the task of extracting Chemical-Disease Relations from PubMed abstracts. A first version of the approach was applied during the participation in the BioCreative V track 3, both in Disease Named Entity Recognition and Normalization (DNER) and in Chemical-induced diseases (CID) relation extraction. For both tasks, we have adopted a general purpose approach based on machine learning techniques integrated with a limited number of domain-specific knowledge resources and using freely available tools for preprocessing data. Crucially, the system only uses the data sets provided by the organizers. The aim is to design an easily portable approach with a limited need of domain-specific knowledge resources. In the participation in the BioCreative V task, we ranked 5 out of 16 in DNER, and 7 out of 18 in CID. In this article, we present our follow-up study in particular on CID by performing further experiments, extending our approach and improving the performance. PMID- 27189610 TI - BioSharing: curated and crowd-sourced metadata standards, databases and data policies in the life sciences. AB - BioSharing (http://www.biosharing.org) is a manually curated, searchable portal of three linked registries. These resources cover standards (terminologies, formats and models, and reporting guidelines), databases, and data policies in the life sciences, broadly encompassing the biological, environmental and biomedical sciences. Launched in 2011 and built by the same core team as the successful MIBBI portal, BioSharing harnesses community curation to collate and cross-reference resources across the life sciences from around the world. BioSharing makes these resources findable and accessible (the core of the FAIR principle). Every record is designed to be interlinked, providing a detailed description not only on the resource itself, but also on its relations with other life science infrastructures. Serving a variety of stakeholders, BioSharing cultivates a growing community, to which it offers diverse benefits. It is a resource for funding bodies and journal publishers to navigate the metadata landscape of the biological sciences; an educational resource for librarians and information advisors; a publicising platform for standard and database developers/curators; and a research tool for bench and computer scientists to plan their work. BioSharing is working with an increasing number of journals and other registries, for example linking standards and databases to training material and tools. Driven by an international Advisory Board, the BioSharing user-base has grown by over 40% (by unique IP address), in the last year thanks to successful engagement with researchers, publishers, librarians, developers and other stakeholders via several routes, including a joint RDA/Force11 working group and a collaboration with the International Society for Biocuration. In this article, we describe BioSharing, with a particular focus on community-led curation.Database URL: https://www.biosharing.org. PMID- 27189611 TI - 'RE:fine drugs': an interactive dashboard to access drug repurposing opportunities. AB - The process of discovering new drugs has been extremely costly and slow in the last decades despite enormous investment in pharmaceutical research. Drug repurposing enables researchers to speed up the process of discovering other conditions that existing drugs can effectively treat, with low cost and fast FDA approval. Here, we introduce 'RE:fine Drugs', a freely available interactive website for integrated search and discovery of drug repurposing candidates from GWAS and PheWAS repurposing datasets constructed using previously reported methods in Nature Biotechnology. 'RE:fine Drugs' demonstrates the possibilities to identify and prioritize novelty of candidates for drug repurposing based on the theory of transitive Drug-Gene-Disease triads. This public website provides a starting point for research, industry, clinical and regulatory communities to accelerate the investigation and validation of new therapeutic use of old drugs.Database URL: http://drug-repurposing.nationwidechildrens.org. PMID- 27189612 TI - Occurrence, composition and risk assessment of antibiotics in soils from Kenya, Africa. AB - Antibiotics can accumulate in soils via different ways, which may pose serious threat to ecological environment of soil and quality of agricultural products. In this study, the occurrence of 12 antibiotics including four sulfonamides (SAs), four tetracyclines (TETs) and four fluoroquinolones (FQs) was investigated in soils from four sampling sites of Kenya (Mai Mahiu, Narok, Mount Suswa Conservancy, and Juja), Africa. The soils in suburban area of Narok had the highest average concentrations of total 12 antibiotics with an average value of 43.64 MUg kg(-1) dw (dry weight), followed by Mai Mahiu (26.70 MUg kg(-1) dw), Juja (24.41 MUg kg(-1) dw) and Mount Suswa Conservancy (12.21 MUg kg(-1) dw). Sulfamethoxazole, sulfamethazine, oxytetracycline, and enrofloxacin were identified as the main antibiotics polluted in soils. Total organic carbon may influence the distribution of SAs in Narok and FQs in Juja. Ecological risk analysis based on the risk quotient showed that SAs detected in soils have higher risk compared to TETs and FQs. PMID- 27189613 TI - The neonicotinoid pesticide, imidacloprid, affects Bombus impatiens (bumblebee) sonication behavior when consumed at doses below the LD50. AB - We investigated changes in sonication (or buzz-pollination) behavior of Bombus impatiens bumblebees, after consumption of the neonicotinoid pesticide, imidacloprid. We measured sonication frequency, sonication length, and flight (wing beat) frequency of marked bees collecting pollen from Solanum lycopsersicum (tomato), and then randomly assigned bees to consume 0, 0.0515, 0.515, or 5.15 ng of imidacloprid. We recorded the number of bees in each treatment group that resumed sonication behavior after consuming imidacloprid, and re-measured sonication and flight behavior for these bees. We did not find evidence that consuming 0.0515 ng imidacloprid affected the sonication length, sonication frequency, or flight frequency for bees that sonicated after consuming imidacloprid; we were unable to test changes in these variables for bees that consumed 0.515 or 5.15 ng because we did not observe enough of these bees sonicating after treatment. We performed Cox proportional hazard regression to determine whether consuming imidacloprid affected the probability of engaging in further sonication behavior on S. lycopersicum and found that bumblebees who consumed 0.515 or 5.15 ng of imidacloprid were significantly less likely to sonicate after treatment than bees who consumed no imidacloprid. At the end of the experiment, we classified bees as dead or alive; our data suggest a trend of increasing mortality with higher doses of imidacloprid. Our results show that even modest doses of imidacloprid can significantly affect the likelihood of bumblebees engaging in sonication, a behavior critical for the pollination of a variety of crops and other plants. PMID- 27189614 TI - Randomized controlled pilot trial of mindfulness-based stress reduction compared to psychoeducational support for persistently fatigued breast and colorectal cancer survivors. AB - PURPOSE: Cancer-related fatigue (CRF) is a disruptive symptom for many survivors. Despite promising evidence for efficacy of mindfulness-based stress reduction (MBSR) in reducing CRF, no trials comparing it to an active comparator for fatigued survivors have been published. The purpose of this trial was to compare MBSR to psychoeducation for CRF and associated symptoms. METHODS: Breast (n = 60) and colorectal (n = 11) cancer survivors (stage 0-III) with clinically significant CRF after completing chemotherapy and/or radiation therapy an average of 28 months prior to enrollment were randomized to MBSR or psychoeducation/support groups (PES). MBSR focused on mindfulness training; PES focused on CRF self-management. Outcomes included CRF interference (primary), CRF severity and global improvement, vitality, depression, anxiety, sleep disturbance, and pain. Outcomes were assessed at baseline (T1), post-intervention (T2), and 6-month follow-up (T3) using intent-to-treat analysis. RESULTS: Between group differences in CRF interference were not significant at any time point; however, there was a trend favoring MBSR (d = -0.46, p = 0.073) at T2. MBSR participants reported significantly greater improvement in vitality (d = 0.53, p = 0.003) and were more likely to report CRF as moderately to completely improved compared to the PES group (chi2 (1) = 4.1765, p = 0.041) at T2. MBSR participants also reported significantly greater reductions in pain at T2 (d = 0.53, p = 0.014). In addition, both MBSR and PES produced moderate-to-large and significant within-group improvements in all fatigue outcomes, depression, anxiety, and sleep at T2 and T3 compared to T1. CONCLUSION: MBSR and PES appear efficacious for CRF and related symptoms. Larger trials including a usual care arm are warranted. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01724333. PMID- 27189615 TI - Chamomile infusion cryotherapy to prevent oral mucositis induced by chemotherapy: a pilot study. AB - PURPOSE: The aim of this study is to compare cryotherapy made only with water and cryotherapy made with chamomile infusion for prevention and reduction of intensity of oral mucositis in patients with cancer receiving 5-fluorouracil and leucovorin. METHOD: This is a randomized pilot study with two groups: cryotherapy made only with water (control group, n = 18) and cryotherapy made with chamomile infusion (chamomile group, n = 20). Both groups were instructed to swish the ice around in their oral cavity for at least 30 min during chemotherapy. Assessment of oral mucosa occurred on days 8, 15, and 22 after the first day of chemotherapy. RESULTS: Fifty percent of the patients in the control and 30 % in the chamomile group developed oral mucositis. Mouth pain score was higher in patients in the control group on all evaluations (p = 0.02 for day 8, p = 0.09 for day 15, and p = 0.14 for day 22). Patients in the chamomile group never developed mucositis with grade 2 or higher. Presence of ulceration was statistically significant on day 8 (16 % in the control vs. 0 % in the chamomile group, p = 0.10), but not in days 15 and 22, although 11 % still had ulcerations in the control group and none in the chamomile group. CONCLUSION: The occurrence of oral mucositis was lower in patients in the chamomile group than in the control group. When compared to the controls, the chamomile group presented less mouth pain and had no ulcerations. Cryotherapy was well tolerated by both groups, and no toxicity related to chamomile was identified. PMID- 27189616 TI - Determinants of exercise adherence and contamination in a randomized controlled trial in cancer patients during and after allogeneic HCT. AB - BACKGROUND: Evidence from randomized controlled trials is growing that exercise interventions are beneficial in cancer patients receiving allogeneic stem cell transplantation (allo-HCT). However, information about adherence to exercise interventions and exercise contamination in control groups is lacking. This information is crucial for the interpretation of study results. We therefore examined the determinants of exercise adherence and contamination in different treatment periods during (inpatient) and after (outpatient) allo-HCT. METHODS: One hundred fifty-three patients scheduled for allo-HCT were randomized to a 1 year partly supervised exercise intervention (endurance and resistance exercise) or to a control group. Adherence was assessed via exercise logs and contamination via questionnaires. RESULTS: Adherence varied between 66 % (inpatient) and 78 % (outpatient) in different treatment periods. During (inpatient) transplantation period, higher adherence was significantly associated with lower fatigue (P = 0.004) and with having children at home (P = 0.049). Adherence after discharge was positively associated with endurance performance (P = 0.003); higher adherence after day 100 was associated with exercise activity prior allo-HCT (P = 0.010) and higher adherence after discharge (P = 0.001). Contamination among controls was high with 54 % and significantly associated with muscle strength (P = 0.025) and fatigue (P = 0.050). CONCLUSION: Exercise adherence in different treatment periods was determined by different variables, and contamination among controls was evident. These findings may have important implications for correct interpretation of randomized exercise intervention trials. PMID- 27189617 TI - A Review on Microdialysis Calibration Methods: the Theory and Current Related Efforts. AB - Microdialysis is a sampling technique first introduced in the late 1950s. Although this technique was originally designed to study endogenous compounds in animal brain, it is later modified to be used in other organs. Additionally, microdialysis is not only able to collect unbound concentration of compounds from tissue sites; this technique can also be used to deliver exogenous compounds to a designated area. Due to its versatility, microdialysis technique is widely employed in a number of areas, including biomedical research. However, for most in vivo studies, the concentration of substance obtained directly from the microdialysis technique does not accurately describe the concentration of the substance on-site. In order to relate the results collected from microdialysis to the actual in vivo condition, a calibration method is required. To date, various microdialysis calibration methods have been reported, with each method being capable to provide valuable insights of the technique itself and its applications. This paper aims to provide a critical review on various calibration methods used in microdialysis applications, inclusive of a detailed description of the microdialysis technique itself to start with. It is expected that this article shall review in detail, the various calibration methods employed, present examples of work related to each calibration method including clinical efforts, plus the advantages and disadvantages of each of the methods. PMID- 27189620 TI - Hypertension is the primary component of metabolic syndrome associated with pathologic features of kidney cancer. AB - PURPOSE: To determine whether individual and/or cumulative components of metabolic syndrome (obesity, hypertension, dyslipidemia, and hyperglycemia) are associated with pathologic features of kidney cancer. PATIENTS AND METHODS: A review of our kidney tumor database identified 462 patients who underwent partial or radical nephrectomy for renal cell carcinoma. The NCEP ATP-III criteria were used to define metabolic syndrome (MetS). Linear fixed effects modeling and ordinal logistic regression examined the relationship between MetS (individual and cumulative components) and pathologic characteristics. RESULTS: Two hundred and seventy-eight men and 184 women with a median age of 58 years, BMI of 31 kg/m2, tumor size of 3.7 cm, and nephrometry score of 6 were included. Ninety seven (21 %) patients met NCEP ATP-III criteria for MetS. Hypertension was the only individual component of MetS associated with pathologic features of kidney cancer including increased tumor size [geometric mean ratio 1.17 (1.05-1.32), P = 0.03], higher tumor grade [OR 1.49 (1.03-2.17), P = 0.04], increasing nephrometry score [OR 1.77 (1.28-2.48), P = 0.001], and non-clear cell histology [OR 1.42 (1.01-2.02), P = 0.05]. Furthermore, combinations of MetS components were associated with increased tumor grade (P = 0.02), tumor stage (P = 0.02), nephrometry score (P <= 0.001), and non-clear cell histology (P = 0.02), only when hypertension was included. CONCLUSION: MetS is composed of four risk factors each implicated in carcinogenesis. We identified hypertension as the primary component associated with specific pathologic features of kidney cancer. Further studies are necessary to elucidate whether the effect of hypertension is a function of severity and/or chronicity. PMID- 27189618 TI - miR-744 and miR-224 Downregulate Npas4 and Affect Lineage Differentiation Potential and Neurite Development During Neural Differentiation of Mouse Embryonic Stem Cells. AB - Neuronal PAS domain protein 4 (Npas4) is a brain-specific transcription factor whose expression is enriched in neurogenic regions of the brain. In addition, it was demonstrated that Npas4 expression is dynamic and highly regulated during neural differentiation of embryonic stem cells (ESCs). While these findings implicate a role for Npas4 in neurogenesis, the underlying mechanisms of regulation remain unknown. Given that growing evidence suggests that microRNAs (miRNAs) play important roles in both embryonic and adult neurogenesis, we reasoned that miRNAs are good candidates for regulating Npas4 expression during neural differentiation of ESCs. In this study, we utilized the small RNA sequencing method to profile miRNA expression during neural differentiation of mouse ESCs. Two differentially expressed miRNAs were identified to be able to significantly reduce reporter gene activity by targeting the Npas4 3'UTR, namely miR-744 and miR-224. More importantly, ectopic expression of these miRNAs during neural differentiation resulted in downregulation of endogenous Npas4 expression. Subsequent functional analysis revealed that overexpression of either miR-744 or miR-224 delayed early neural differentiation, reduced GABAergic neuron production and inhibited neurite outgrowth. Collectively, our findings indicate that Npas4 not only functions at the early stages of neural differentiation but may also, in part, contribute to neuronal subtype specification and neurite development. PMID- 27189619 TI - Analysis of Extracellular Nucleotide Metabolism in Adult Zebrafish After Embryological Exposure to Valproic Acid. AB - Autism is a neurodevelopmental disorder characterized by symptoms related to stereotyped movements, deficits in social interaction, impaired communication, anxiety, hyperactivity, and the presence of restricted interests. Evidence indicates an important role of extracellular ATP and adenosine as signaling molecules in autism. ATP hydrolysis by ectonucleotidases is an important source of adenosine, and adenosine deaminase (ADA) contributes to the control of the nucleoside concentrations. Considering zebrafish is an animal model that may contribute towards to understanding the mechanisms that underlie social behavior, we investigated the purinergic signaling in a model of embryological exposure to valproic acid (VPA) that induces social interaction deficit in adult zebrafish. We demonstrated embryological exposure to VPA did not change ATP and ADP hydrolysis in zebrafish at 120 dpf, and the cytosolic (soluble) ADA activity was not altered. However, we observed an increase of AMP hydrolysis (12.5 %) whereas the ecto-ADA activity was decreased (19.2 %) in adult zebrafish submitted to embryological exposure to VPA. Quantitative reverse transcription PCR (RT-PCR) analysis showed changes on ntpd8, ADA 2.1, and A2a1 mRNA transcript levels. Brain ATP metabolism showed a rapid catabolism of ATP and ADP, whereas the extracellular metabolism of AMP and adenosine (ADO) occurred slowly. We demonstrated that embryological exposure to VPA altered biochemical and molecular parameters related to purinergic system in adult zebrafish. These findings indicate that the enzyme activities involved in the control of ATP and adenosine levels may be involved in the pathophysiological mechanisms of diseases related to the impairment of social interaction, such as autism. PMID- 27189622 TI - An Algorithm for Creating Prognostic Systems for Cancer. AB - The TNM staging system is universally used for classification of cancer. This system is limited since it uses only three factors (tumor size, extent of spread to lymph nodes, and status of distant metastasis) to generate stage groups. To provide a more accurate description of cancer and thus better patient care, additional factors or variables should be used to classify cancer. In this paper we propose a hierarchical clustering algorithm to develop prognostic systems that classify cancer according to multiple prognostic factors. This algorithm has many potential applications in augmenting the data currently obtained in a staging system by allowing more prognostic factors to be incorporated. The algorithm clusters combinations of prognostic factors that are formed using categories of factors. The dissimilarity between two combinations is determined by the area between two corresponding survival curves. Groups from cutting the dendrogram and survival curves of the individual groups define our prognostic systems that classify patients using survival outcomes. A demonstration of the proposed algorithm is given for patients with breast cancer from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. PMID- 27189621 TI - Genome sequence and comparative analysis of clavicipitaceous insect-pathogenic fungus Aschersonia badia with Metarhizium spp. AB - BACKGROUND: Aschersonia badia [(Ab) Teleomorph: Hypocrella siamensis] is an entomopathogenic fungus that specifically infects scale insects and whiteflies. We present the whole genome sequence of Ab and its comparison with two clavicipitaceous fungi Metarhizium robertsii (MR: generalist entomopathogen) and M. acridum (MAC: acridid-specific entomopathogen) that exhibit variable host preferences. Here, through comparative analysis of pathogen-host interacting genes, carbohydrate active enzymes, secondary metabolite biosynthesis genes, and sexuality genes, we explore the proteins with possible virulence functions in clavicipitaceous fungi. Comprehensive overview of GH18 family chitinases has been provided to decipher the role of chitinases in claviceptaceous fungi that are either host specific or generalists. RESULTS: We report the 28.8 Mb draft genome of Ab and its comparative genome analysis with MR and MAC. The comparative analyses suggests expansion in pathogen-host interacting gene families and carbohydrate active enzyme families in MR, whilst their contraction in Ab and MAC genomes. The multi-modular NRPS gene (dtxS1) responsible for biosynthesis of the secondary metabolite destruxin in MR is not conserved in Ab, similar to the specialist pathogen MAC. An additional siderophore biosynthetic gene responsible for acquisition of iron was identified in MR. Further, the domain survey of chitinases suggest that the CBM50 (LysM) domains, which participate in chitin binding functions, were not observed in MAC, but were present in Ab and MR. However, apparent differences in frequency of CBM50 domains associated with chitinases of Ab and MR was identified, where MR chitinases displayed a higher proportion of associated CBM50 domains than Ab chitinases. CONCLUSIONS: This study suggests differences in distribution of dtxS1 and chitinases in specialists (Ab and MAC) and generalists (MR) fungi. Our analysis also suggests the presence of a siderophore biosynthetic gene in the MR genome which perhaps aids in enhanced virulence potential and host range. The variation in association of CBMs, being higher in generalists (MR) and lower in specialists (Ab and MAC) fungi may further be responsible for the differences in host affiliation. PMID- 27189623 TI - Distributed Denial of Service Attack Source Detection Using Efficient Traceback Technique (ETT) in Cloud-Assisted Healthcare Environment. AB - Security and privacy are the first and foremost concerns that should be given special attention when dealing with Wireless Body Area Networks (WBANs). As WBAN sensors operate in an unattended environment and carry critical patient health information, Distributed Denial of Service (DDoS) attack is one of the major attacks in WBAN environment that not only exhausts the available resources but also influence the reliability of information being transmitted. This research work is an extension of our previous work in which a machine learning based attack detection algorithm is proposed to detect DDoS attack in WBAN environment. However, in order to avoid complexity, no consideration was given to the traceback mechanism. During traceback, the challenge lies in reconstructing the attack path leading to identify the attack source. Among existing traceback techniques, Probabilistic Packet Marking (PPM) approach is the most commonly used technique in conventional IP- based networks. However, since marking probability assignment has significant effect on both the convergence time and performance of a scheme, it is not directly applicable in WBAN environment due to high convergence time and overhead on intermediate nodes. Therefore, in this paper we have proposed a new scheme called Efficient Traceback Technique (ETT) based on Dynamic Probability Packet Marking (DPPM) approach and uses MAC header in place of IP header. Instead of using fixed marking probability, the proposed scheme uses variable marking probability based on the number of hops travelled by a packet to reach the target node. Finally, path reconstruction algorithms are proposed to traceback an attacker. Evaluation and simulation results indicate that the proposed solution outperforms fixed PPM in terms of convergence time and computational overhead on nodes. PMID- 27189624 TI - A cohort study of the impact and acquisition of naspharyngeal carriage of Streptococcus pneumoniae during the Hajj. AB - BACKGROUND: The annual Muslim pilgrimage attracts over two million pilgrims who gather in a limited time and space. The pilgrimage carries the potential risk of increase risk of the acquisition of Streptococcus pneumonia. In this cohort study, we evaluate the effect of the Hajj on the prevalence of pneumococcal serotype nasopharyngeal carriage in the Hajj pilgrim population. The secondary objective is to evaluate the effects of the mass gathering on carriage of invasive pneumococcal serotypes. METHODS: This is a prospective cohort study with two data collection periods: at the beginning and at the end of the Hajj. Nasopharyngeal samples were taken via a standardized swabbing method. RESULTS: A total of 1175 pilgrims were enrolled at the beginning of the study and 1155 (98.3%) were included at the second part of the study. The pre-Hajj samples were obtained at a mean of 0 days and the post-Hajj sampling occurred at a mean of 15 days after arrival to Saudi Arabia. The overall carriage rate of Streptococcus pneumoniae in the pre- and post-Hajj was 1.8% and 7.1% (P = 0.0016). The potential coverage of the 7-valent pneumococcal conjugate vaccine (PCV7), PCV10 and PCV13 were 15.5%, 19.1%; and 35.5%, respectively. The coverage for the 23 valent pneumococcal polysaccharide vaccine (PPV23) was 40%. CONCLUSION: Although there was an increase in the acquisition of S. pneumoniae, its magnitude is low which does not support public health recommendations for general pneumococcal vaccination of pilgrims except those at risk. PMID- 27189626 TI - Unblocking the cancer drug development bottleneck via innovative partnering. PMID- 27189625 TI - Icatibant Compared to Steroids and Antihistamines for ACE-Inhibitor-Induced Angioedema. AB - Article chosen Bas M, Greve J, Stelter K, et al. A Randomized Trial of Icatibant in ACE-Inhibitor-Induced Angioedema. N Engl J Med 2015;372:418-25. doi:10.1056/NEJMoa1312524. PMID- 27189627 TI - Stability and Crestal Bone Behavior Following Simultaneous Placement of Multiple Dental Implants (Two or More) with the Bone Splitting Technique: A Clinical and Radiographic Evaluation. AB - PURPOSE: The present study aimed to measure the implant stability quotient (ISQ) values at three different time points after surgical procedures and crestal bone behavior in multiple implants (two or more) installed simultaneously with the bone splitting technique. MATERIALS AND METHODS: For this study, 45 patients with different edentulous areas in the maxilla were selected, and a total of 114 dental implants were installed. Implant stability was measured by resonance frequency analysis immediately following implant placement to assess immediate stability (time 1) and stability at 90 days (time 2), and 150 days (time 3). Crestal bone height was measured in peri-apical radiographs at 90 and 150 days after implantation in relation to each implant shoulder, given that the implants were installed at the level of the crestal bone. RESULTS: Six implants were not osseointegrated. Overall, the means and standard deviations of the ISQ values were 60.3 +/- 4.94 (95% confidence interval [CI], 44-69) at baseline, 66.6 +/- 5.28 (95% CI, 49-75) at 90 days, and 72.1 +/- 4.28 (95% CI, 59-79) at 150 days (p < 0.0001). The mean marginal bone loss of the implants was 1.11 +/- 0.61 mm on the mesial side and 1.17 +/- 0.61 mm on the distal side at time 2, and 1.73 +/- 0.68 mm on the mesial side and 1.79 +/- 0.70 mm on the distal side at time 3. A strong positive correlation between implant stability and bone loss was detected (p < 0.0001). CONCLUSIONS: Within the limits of this study, the bone splitting technique with simultaneous implant installation exhibited a good success rate with respect to the osseointegration index but requires attention with respect to crestal bone behavior. PMID- 27189628 TI - Distribution of HLA-DRB1 and HLA-DQB1 alleles in Lak population of Iran. AB - Human leukocyte antigen (HLA) genes are the most polymorphic loci in the human genome and encode the highly polymorphic molecules critically involved in immune responses. Anthropological studies based on highly polymorphic HLA genes provide useful information for bone marrow donor registry, forensic medicine, disease association studies, as well as designing peptide vaccines against tumors, and infectious or autoimmune diseases. The aim of this study was to determine the HLA DRB1 and HLA-DQB1 allele frequencies in 100 unrelated Lak individuals from Lorestan province of Iran. Finally, we compared the results with those previously described in four other Iranian populations. Commercial HLA-Type kits were used for determination of the HLA-DRB1 and HLA-DQB1 allele frequencies. Differences between populations in the distribution of HLA-DRB1 and HLA-DQB1 alleles were estimated by chi2 test with Yate's correction and Fisher's exact test. The most frequent HLA-DRB1 alleles were (*)1103=4 (23%), (*)1502 (9.5%), (*)0701 (9%), (*)0301 (8.5%), (*)1101 (7.5%) and (*)1501 (6%) while HLA-DQB1(*)0301 (40%), (*)0201 (15%), (*)0502 (10.5%), (*)0303 (10%), (*)0602=3 (9.5%), and (*)0501 (7.5%) were the most frequent alleles in Lak population. HLA-DRB1(*)0409, (*)0804, (*)1102, (*)1112, (*)1405, and HLA-DQB1(*)0503, (*)0604 were the least observed frequencies in Lak population. Our results based on HLA-DRB1 and HLA DQB1 allele frequencies showed that the Lak population possesses the previously reported general features of the Lur and Kurd populations but still with unique, decreased or increased frequencies of several alleles. In other words, the Lak population is close to Lurs Khorramabadi and Kurd but far from Lurs Kohkiloyeh/Boyerahmad and Bakhtiari. PMID- 27189629 TI - Can cyclist safety be improved with intelligent transport systems? AB - In recent years, Intelligent Transport Systems (ITS) have assisted in the decrease of road traffic fatalities, particularly amongst passenger car occupants. Vulnerable Road Users (VRUs) such as pedestrians, cyclists, moped riders and motorcyclists, however, have not been that much in focus when developing ITS. Therefore, there is a clear need for ITS which specifically address VRUs as an integrated element of the traffic system. This paper presents the results of a quantitative safety impact assessment of five systems that were estimated to have high potential to improve the safety of cyclists, namely: Blind Spot Detection (BSD), Bicycle to Vehicle communication (B2V), Intersection safety (INS), Pedestrian and Cyclist Detection System+Emergency Braking (PCDS+EBR) and VRU Beacon System (VBS). An ex-ante assessment method proposed by Kulmala (2010) targeted to assess the effects of ITS for cars was applied and further developed in this study to assess the safety impacts of ITS specifically designed for VRUs. The main results of the assessment showed that all investigated systems affect cyclist safety in a positive way by preventing fatalities and injuries. The estimates considering 2012 accident data and full penetration showed that the highest effects could be obtained by the implementation of PCDS+EBR and B2V, whereas VBS had the lowest effect. The estimated yearly reduction in cyclist fatalities in the EU-28 varied between 77 and 286 per system. A forecast for 2030, taking into accounts the estimated accident trends and penetration rates, showed the highest effects for PCDS+EBR and BSD. PMID- 27189630 TI - Quantum state transfer via Bloch oscillations. AB - The realization of reliable quantum channels, able to transfer a quantum state with high fidelity, is a fundamental step in the construction of scalable quantum devices. In this paper we describe a transmission scheme based on the genuinely quantum effect known as Bloch oscillations. The proposed protocol makes it possible to carry a quantum state over different distances with a minimal engineering of the transmission medium and can be implemented and verified on current quantum technology hardware. PMID- 27189631 TI - In-Water and Neat Batch and Continuous-Flow Direct Esterification and Transesterification by a Porous Polymeric Acid Catalyst. AB - A porous phenolsulphonic acid-formaldehyde resin (PAFR) was developed. The heterogeneous catalyst PAFR was applied to the esterification of carboxylic acids and alcohols, affording the carboxylic acid esters in a yield of up to 95% where water was not removed from the reaction mixture. Surprisingly, the esterification in water as a solvent proceeded to afford the desired esters in high yield. PAFR provided the corresponding esters in higher yield than other homogeneous and heterogeneous catalysts. The transesterification of alcohols and esters was also investigated by using PAFR, giving the corresponding esters. PAFR was applied to the batch-wise and continuous-flow production of biodiesel fuel FAME. The PAFR packed flow reactor that was developed for the synthesis of carboxylic acids and FAME worked for four days without loss of its catalytic activity. PMID- 27189632 TI - Identification and Evaluation of Novel MicroRNA Biomarkers in Plasma and Feces Associated with Drug-induced Intestinal Toxicity. AB - Gastrointestinal toxicity is dose limiting with many therapeutic and anticancer agents. Real-time, noninvasive detection of markers of toxicity in biofluids is advantageous. Ongoing research has revealed microRNAs as potential diagnostic and predictive biomarkers for the detection of select organ toxicities. To study the potential utility of microRNA biomarkers of intestinal injury in a preclinical toxicology species, we evaluated 3 rodent models of drug-induced intestinal toxicity, each with a distinct mechanism of toxicity. MiR-215 and miR-194 were identified as putative intestinal toxicity biomarkers. Both were evaluated in plasma and feces and compared to plasma citrulline, an established intestinal injury biomarker. Following intestinal toxicant dosing, microRNA changes in feces and plasma were detected noninvasively and correlated with histologic evidence of intestinal injury. Fecal miR-215 and miR-194 levels increased, and plasma miR-215 decreased in a dose- and time-dependent manner. Dose-dependent decreases in plasma miR-215 levels also preceded and correlated positively with plasma citrulline modulation, suggesting miR-215 is a more sensitive biomarker. Moreover, during the drug-free recovery phase, plasma miR-215 returned to predose levels, supporting a corresponding recovery of histologic lesions. Despite limitations, this study provides preliminary evidence that select microRNAs have the potential to act as noninvasive, sensitive, and quantitative biomarkers of intestinal injury. PMID- 27189633 TI - Hierarchically branched Fe2O3@TiO2 nanorod arrays for photoelectrochemical water splitting: facile synthesis and enhanced photoelectrochemical performance. AB - Highly photoactive and durable photoanode materials are the key to photoelectrochemical water splitting. In this paper, hierarchically branched Fe2O3@TiO2 nanorod arrays (denoted as Fe2O3@TiO2 BNRs) composed of a long Fe2O3 trunk and numerous short TiO2 nanorod branches were fabricated and used as photoanodes for water splitting. Significant improvement of photoelectrochemical water splitting performance was observed based on Fe2O3@TiO2 BNRs. The photocurrent density of Fe2O3@TiO2 BNRs reaches up to 1.3 mA cm(-2) at 1.23 V versus RHE, which is 10 times higher than that of pristine Fe2O3 nanorod arrays under the same conditions. Furthermore, an obvious cathodic shift in the onset potential of photocurrent was observed in the Fe2O3@TiO2 BNRs. More significantly, the Fe2O3@TiO2 BNRs are quite stable even after 3600 s continuous illumination, and the photocurrent density shows almost no decay. Finally, a tentative mechanism was proposed to explain the superior performance of Fe2O3@TiO2 BNRs for PEC water splitting and discussed in detail on the basis of our experimental results. PMID- 27189635 TI - Differential expression of heat shock protein 90, 70, 60 in chicken muscles postmortem and its relationship with meat quality. AB - OBJECTIVE: The aim of this study was to investigate the expression of heat shock protein (HSP) 90, 70, and 60 in chicken muscles and their possible relationship with quality traits of meat. METHODS: The breast muscles from one hundred broiler chickens were analyzed for drip loss and other quality parameters, and the levels of heat shock protein (HSP) 90, 70, and 60 were determined by immunoblots. RESULTS: Based on the data, chicken breast muscles were segregated into low (drip loss<=5%), intermediate (5%=9.5) drip loss groups. The expression of HSP90 and HSP60 were significantly lower in the high drip loss group compared to that in the low and intermediate drip loss group (p<0.05), while HSP70 was equivalent in abundance in all groups (p>0.05). CONCLUSION: Results of this study suggests that higher levels of HSP90 and HSP60 may be advantageous for maintenance of cell function and reduction of water loss, and they could act as potential indicator for better water holding capacity of meat. PMID- 27189636 TI - Effectiveness of Phytogenic Feed Additive as Alternative to Bacitracin Methylene Disalicylate on Hematological Parameters, Intestinal Histomorphology and Microbial Population and Production Performance of Japanese Quails. AB - This study was conducted to evaluate the effects of phytogenic additive and antibiotic growth promoter in laying Japanese quails. One hundred and sixty five quails were divided into three groups of 5 replicates and 11 quails (8 females and 3 males) in each replicate. Treatment 1 was fed control diet, treatment 2 was fed control diet supplemented with 0.05% bacitracin methylene disalicylate as antibiotic growth promoter and treatment 3 was fed control diet supplemented with 0.1% phytogenic feed additive (PFA) for two periods of 3 weeks each from 37 to 42 weeks of age. Results showed that egg production, eggshell strength, eggshell weight, villus height and villus height to crypt depth ratio were significantly (p<=0.05) increased and feed consumption, feed conversion ratio, albumen, Haugh unit, cholesterol, low-density lipoprotein, alanine transaminase, gamma glutamyltransferase, alkaline phosphatase, high-density lipoprotein, triglyceride, number of goblet cell, crypt depth and intestinal bacterial population of Coliforms, Salmonella and E. coli were significantly (p<=0.05) decreased in PFA fed group. It is concluded that addition of PFA containing phytomolecules and organic acids as main ingredients could significantly improve the production parameters and the general health of laying quails as an alternative to antibiotic growth promoters. PMID- 27189637 TI - Maternal Origin of Turkish and Iranian Native Chickens Inferred from Mitochondrial DNA D-loop Sequences. AB - To assess genetic diversity and maternal origin of Turkish and Iranian native chicken breeds, we analyzed the mtDNA D-loop sequences of 222 chickens from 2 Turkish (Denizli and Gerze) and 7 Iranian (White Marandi, Black Marandi, Naked Neck, Common Breed, Lari, West Azarbaijan, and New Hampshire) native chicken breeds, together with the available reference sequences of G. gallus gallus in GenBank. The haplotype diversity was estimated as 0.24+/-0.01 and 0.36+/-0.02 for Turkish and Iranian populations, respectively. In total, 19 haplotypes were observed from 24 polymorphic sites in Turkish and Iranian native chicken populations. Two different clades or haplogroups (A and E) were found in Turkish and Iranian chickens. Clade A haplotypes were found only in White Marandi, Common Breed and New Hampshire populations. Clade E haplotypes, which are quite common, were observed in Turkish and Iranian populations with 18 different haplotypes, of which Turkish and Iranian chickens, Clade E, haplotype 1 (TRIRE1) was a major haplotype with the frequency of 81.5% (181/222) across all breeds. Compared to red jungle fowl, Turkish and Iranian chicken breeds are closely related to each other. These results suggest that Turkish and Iranian chickens originated from the same region, the Indian subcontinent. Our results will provide reliable basic information for mtDNA haplotypes of Turkish and Iranian chickens and for studying the origin of domestic chickens. PMID- 27189638 TI - Lower omega-6/omega-3 Polyunsaturated Fatty Acid Ratios Decrease Fat Deposition by Inhibiting Fat Synthesis in Gosling. AB - The objective of the current study was to investigate the effects of dietary omega-6/omega-3 polyunsaturated fatty acid (PUFA) ratios on lipid metabolism in goslings. One hundred and sixty 21-day-old Yangzhou geese of similar weight were randomly divided into 4 groups. They were fed different PUFA-supplemented diets (the 4 diets had omega-6/omega-3 PUFA ratios of 12:1, 9:1, 6:1, or 3:1). The geese were slaughtered and samples of liver and muscle were collected at day 70. The activities and the gene expression of enzymes involved in lipid metabolism were measured. The results show that the activities of acetyl coenzyme A carboxylase (ACC), malic enzyme (ME), and fatty acid synthase (FAS) were lower (p<0.05), but the activities of hepatic lipase (HL) and lipoprotein lipase (LPL) were higher (p<0.05), in the liver and the muscle from the 3:1 and 6:1 groups compared with those in the 9:1 and 12:1 groups. Expression of the genes for FAS (p<0.01), ME (p<0.01) and ACC (p<0.05) were higher in the muscle of groups fed diets with higher omega-6/omega-3 PUFA ratios. Additionally, in situ hybridization tests showed that the expression intensities of the high density lipoprotein (HDL-R) gene in the 12:1 and 9:1 groups were significantly lower (p<0.01) than that of the 3:1 group in the muscle of goslings. In conclusion, diets containing lower omega-6/omega-3 PUFA ratios (3:1 or 6:1) could decrease fat deposition by inhibiting fat synthesis in goslings. PMID- 27189639 TI - Transport losses in finisher pigs: impact of transport distance and season of the year. AB - OBJECTIVE: The death of animals during transport for slaughter is a major factor indicating the level of welfare in transported animals. The aim of this study was to assess mortality related to the commercial transport of finisher pigs for slaughter in the Czech Republic. METHODS: The inspectors of the State Veterinary Administration of the Czech Republic recorded the numbers of finisher pigs transported to processing plants in the Czech Republic for slaughter and the mortality in these pigs in relation to transport in the period from 2009 to 2014. RESULTS: Our results show that the likelihood of death losses in transported pigs increases with increasing transport distance. The transport-related mortality ranged from 0.049% in pigs transported for distances below 50 km to 0.145% in pigs transported for distances exceeding 300 km. The impact of external air temperature on the transport-related mortality found in our study clearly shows that current transport practices fail to ensure the welfare of pigs transported under other than moderate weather. Particularly cold temperatures below -2 degrees C were associated with increased death losses in winter transport. CONCLUSION: Despite a decreasing trend in the mortality of finisher pigs transported for slaughter in Europe, our study suggests that current transport conditions are not efficient at ensuring the welfare of pigs during transport for longer distances and the protection of pigs against the negative impact of extreme ambient temperatures. Further research should focus on developing practical guidelines to improve the welfare of pigs in transit accordingly. PMID- 27189640 TI - Transcriptome profile of one-month-old lambs' granulosa cells after superstimulation. AB - OBJECTIVE: Superstimulatory treatment of one-month-old lambs can achieve synchronous development of numerous growing follicles. However, these growing follicles cannot complete maturation and ovulation. Oocyte maturation and competence are acquired during follicular development, in which granulosa cells play an essential role. METHODS: In this study, we applied RNA sequencing to analyze and compare gene expression between prepubertal and adult superstimulated follicle granulosa cells in sheep. RESULTS: There were more than 300 genes that significantly differed in expression. Among these differently expressed genes, many extracellular matrix genes (EGF containing Fibulin Like Extracellular Matrix Protein 1, pentraxin 3, adrenomedullin, and osteopontin) were significantly down regulated in the superstimulated follicles. Ingenuity pathway and gene ontology analyses revealed that processes of axonal guidance, cell proliferation and DNA replication were expressed at higher levels in the prepubertal follicles. Epidermal growth factor, T-Box protein 2 and beta-estradiol upstream regulator were predicted to be active in prepubertal follicles. By comparison, tumor protein P53 and let-7 were most active in adult follicles. CONCLUSION: These results may contribute to a better understanding of the mechanisms governing the development of granulosa cells in the growing follicle in prepubertal sheep. PMID- 27189641 TI - Influence of polymer-coated slow-release urea on total tract apparent digestibility, ruminal fermentation and performance of Nellore steers. AB - OBJECTIVE: Two experiments were performed to evaluate the effects of coated slow release urea on nutrient digestion, ruminal fermentation, nitrogen utilization, blood glucose and urea concentration (Exp 1), and average daily gain (ADG; Exp 2) of steers. METHODS: Exp 1: Eight ruminally fistulated steers [503+/-28.5 kg body weight (BW)] were distributed into a d 4*4 Latin square design and assigned to treatments: control (CON), feed grade urea (U2), polymer-coated slow-release urea A (SRA2), and polymer-coated slow-release urea B (SRB2). Dietary urea sources were set at 20 g/kg DM. Exp 2: 84 steers (350.5+/-26.5 kg initial BW) were distributed to treatments: CON, FGU at 10 or 20 g/kg diet DM (U1 and U2, respectively), coated SRA2 at 10 or 20 g/kg diet DM (SRA1 and SRA2, respectively), and coated SRB at 10 or 20 g/kg diet DM (SRB1 and SRB2, respectively). RESULTS: Exp 1: Urea treatments (U2+SRA2+SRB2) decreased (7.4%, p = 0.03) the DM intake and increased (11.4%, p<0.01) crude protein digestibility. Coated slow-release urea (SRA2+SRB2) showed similar nutrient digestibility compwared to feed grade urea (FGU). However, steers fed SRB2 had higher (p = 0.02) DM digestibility compared to those fed SRA2. Urea sources did not affect ruminal fermentation when compared to CON. Although, coated slow-release urea showed lower (p = 0.01) concentration of NH3-N (-10.4%) and acetate to propionate ratio than U2. Coated slow-release urea showed lower (p = 0.02) urinary N and blood urea concentration compared to FGU. Exp 2: Urea sources decreased (p = 0.01) the ADG in relation to CON. Animals fed urea sources at 10 g/kg DM showed higher (12.33%, p = 0.01) ADG compared to those fed urea at 20 g/kg DM. CONCLUSION: Feeding urea decreased the nutrient intake without largely affected the nutrient digestibility. In addition, polymer-coated slow-release urea sources decreased ruminal ammonia concentration and increased ruminal propionate production. Urea at 20 g/kg DM, regardless of source, decreased ADG compared both to CON and diets with urea at 10 g/kg DM. PMID- 27189642 TI - Knockout of Myostatin by Zinc-finger Nuclease in Sheep Fibroblasts and Embryos. AB - Myostatin (MSTN) can negatively regulate the growth and development of skeletal muscle, and natural mutations can cause "double-muscling" trait in animals. In order to block the inhibiting effect of MSTN on muscle growth, we transferred zinc-finger nucleases (ZFN) which targeted sheep MSTN gene into cultured fibroblasts. Gene targeted colonies were isolated from transfected fibroblasts by serial dilution culture and screened by sequencing. Two colonies were identified with mono-allele mutation and one colony with bi-allelic deletion. Further, we introduced the MSTN-ZFN mRNA into sheep embryos by microinjection. Thirteen of thirty-seven parthenogenetic embryos were targeted by ZFN, with the efficiency of 35%. Our work established the technical foundation for generation of MSTN gene editing sheep by somatic cloning and microinjection ZFN into embryos. PMID- 27189643 TI - Stress, Nutrition, and Intestinal Immune Responses in Pigs - A Review. AB - Modern livestock production became highly intensive and large scaled to increase production efficiency. This production environment could add stressors affecting the health and growth of animals. Major stressors can include environment (air quality and temperature), nutrition, and infection. These stressors can reduce growth performance and alter immune systems at systemic and local levels including the gastrointestinal tract. Heat stress increases the permeability, oxidative stress, and inflammatory responses in the gut. Nutritional stress from fasting, antinutritional compounds, and toxins induces the leakage and destruction of the tight junction proteins in the gut. Fasting is shown to suppress pro-inflammatory cytokines, whereas deoxynivalenol increases the recruitment of intestinal pro-inflammatory cytokines and the level of lymphocytes in the gut. Pathogenic and viral infections such as Enterotoxigenic E. coli (ETEC) and porcine epidemic diarrhea virus can lead to loosening the intestinal epithelial barrier. On the other hand, supplementation of Lactobacillus or Saccharaomyces reduced infectious stress by ETEC. It was noted that major stressors altered the permeability of intestinal barriers and profiles of genes and proteins of pro-inflammatory cytokines and chemokines in mucosal system in pigs. However, it is not sufficient to fully explain the mechanism of the gut immune system in pigs under stress conditions. Correlation and interaction of gut and systemic immune system under major stressors should be better defined to overcome aforementioned obstacles. PMID- 27189644 TI - Effects of Dietary Octacosanol on Growth Performance, Carcass Characteristics and Meat Quality of Broiler Chicks. AB - Octacosanol, which has prominent physiological activities and functions, has been recognized as a potential growth promoter in animals. A total of 392 1-d-old male Arbor Acres broiler chicks with similar body weight were randomly distributed into four dietary groups of seven replicates with 14 birds each supplemented with 0, 12, 24, or 36 mg octacosanol (extracted from rice bran, purity >92%)/kg feed. The feeding trial lasted for six weeks and was divided into the starter (day 1 to 21) and the grower (day 22 to 42) phases. The results showed that the feed conversion ratio (FCR) was significantly improved in broilers fed a diet containing 24 mg/kg octacosanol compared with those fed the control diet in the overall phase (day 1 to 42, p = 0.042). The average daily gain and FCR both showed linear effects in response to dietary supplementation of octacosanol during the overall phase (p = 0.031 and 0.018, respectively). Broilers fed with 24 or 36 mg/kg octacosanol diet showed a higher eviscerated yield, which increased by 5.88% and 4.26% respectively, than those fed the control diet (p = 0.030). The breast muscle yield of broilers fed with 24 mg/kg octacosanol diet increased significantly by 12.15% compared with those fed the control diet (p = 0.047). Eviscerated and breast muscle yield increased linearly with the increase in dietary octacosanol supplementation (p = 0.013 and 0.021, respectively). Broilers fed with 24 or 36 mg/kg octacosanol diet had a greater (p = 0.021) pH45min value in the breast muscle, which was maintained linearly in response to dietary octacosanol supplementation (p = 0.003). There was a significant decrease (p = 0.007) in drip loss value between the octacosanol-added and the control groups. The drip loss showed linear (p = 0.004) and quadratic (p = 0.041) responses with dietary supplementation of octacosanol. These studies indicate that octacosanol is a potentially effective and safe feed additive which may improve feed efficiency and meat quality, and increase eviscerated and breast muscle yield, in broiler chicks. Dietary supplementation of octacosanol at 24 mg/kg diet is regarded as the recommended dosage in the broilers' diet. PMID- 27189645 TI - Fast determination of neonicotinoid insecticides in bee pollen using QuEChERS and ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. AB - In this study, a new method has been developed to determine seven neonicotinoid insecticides (acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, thiacloprid and thiamethoxam) in bee pollen using ultra-high performance liquid chromatography coupled to a selective MS detector (qTOF). An efficient sample treatment involving an optimized quick, easy, cheap, effective, rugged and safe method was proposed. In all cases, average analyte recoveries were between 91 and 105%, and no matrix effect was observed. Chromatographic analysis (6.5 min) was performed on a core-shell technology based column (Kinetex(r) EVO C18 , 50*2.1 mm, 1.7 MUm, 100 A). The mobile phase consisted of 0.1% formic acid in water and 0.1% of formic acid in ACN, with a flow rate of 0.3 mL/min in gradient elution mode. The fully validated method was selective, linear from LOQ to 500 MUg/kg, precise and accurate; relative standard deviation and relative error values were below 8%. Low limits LODs and LOQs were obtained, ranging from 0.6 to 1.3 MUg/kg (LODs) and 2.1 to 4.0 MUg/kg (LOQs). The method was applied to neonicotinoid analysis in several commercial bee pollen samples from different Spanish regions. PMID- 27189647 TI - Digging for known genetic mutations underlying inherited bone and cartilage characteristics and disorders in the dog and cat. AB - Gene mapping projects for many traits in both dogs and cats have yielded new knowledge. Both researchers and the public alike have been fascinated by the inheritance of breed characteristic phenotypes and sporadic disorders. It has been proposed that selective breeding practices have on occasion generated alterations in structure that might be harmful. In this review, simply inherited disorders and characteristics affecting bone and cartilage for which a putative mutation is known are collected. A better understanding of the known inherited basis of skeletal conditions and disorders will assist veterinarians to improve their diagnoses and increase their effectiveness on advising clients on the prevention, management, prognosis and possible treatment of the conditions. PMID- 27189646 TI - No cytotoxicity or genotoxicity of graphene and graphene oxide in murine lung epithelial FE1 cells in vitro. AB - Graphene and graphene oxide receive much attention these years, because they add attractive properties to a wide range of applications and products. Several studies have shown toxicological effects of other carbon-based nanomaterials such as carbon black nanoparticles and carbon nanotubes in vitro and in vivo. Here, we report in-depth physicochemical characterization of three commercial graphene materials, one graphene oxide (GO) and two reduced graphene oxides (rGO) and assess cytotoxicity and genotoxicity in the murine lung epithelial cell line FE1. The studied GO and rGO mainly consisted of 2-3 graphene layers with lateral sizes of 1-2 um. GO had almost equimolar content of C, O, and H while the two rGO materials had lower contents of oxygen with C/O and C/H ratios of 8 and 12.8, respectively. All materials had low levels of endotoxin and low levels of inorganic impurities, which were mainly sulphur, manganese, and silicon. GO generated more ROS than the two rGO materials, but none of the graphene materials influenced cytotoxicity in terms of cell viability and cell proliferation after 24 hr. Furthermore, no genotoxicity was observed using the alkaline comet assay following 3 or 24 hr of exposure. We demonstrate that chemically pure, few layered GO and rGO with comparable lateral size (> 1 um) do not induce significant cytotoxicity or genotoxicity in FE1 cells at relatively high doses (5 200 ug/ml). Environ. Mol. Mutagen. 57:469-482, 2016. (c) 2016 The Authors. Environmental and Molecular Mutagenesis Published by Wiley Periodicals, Inc. PMID- 27189648 TI - Nicotine has deleterious effects on wound healing through increased vasoconstriction. PMID- 27189649 TI - Palladium-Initiated Radical Cascade Stereoselective Iodofluoroalkylation/Cycloisomerization of Ene-vinylidenecyclopropanes. AB - A novel and convenient palladium-initiated radical cascade stereoselective iodofluoroalkylation/cycloisomerization of ene-vinylidenecyclopropanes with fluoroalkyl iodides has been developed. The reaction proceeds under mild reaction conditions with high atom economy and stereoselectivity, thereby allowing an efficient access to a variety of difluoromethylated or perfluoroalkylated pyrrolidines tethered with an alkyl iodide. Two plausible radical pathways for the transformation have been proposed on the basis of the results of control experiments and previous reports, which in one case it was thought that palladium(0) was an initiator rather than a catalyst. PMID- 27189650 TI - Ankle muscle coactivation and its relationship with ankle joint kinematics and kinetics during gait in hemiplegic patients after stroke. AB - INTRODUCTION: Increased ankle muscle coactivation during gait is a compensation strategy for enhancing postural stability in patients after stroke. However, no previous studies have demonstrated that increased ankle muscle coactivation influenced ankle joint movements during gait in patients after stroke. PURPOSE: To investigate the relationship between ankle muscle coactivation and ankle joint movements in hemiplegic patients after stroke. METHODS: Seventeen patients after stroke participated. The coactivation index (CoI) at the ankle joint was calculated separately for the first and second double support (DS1 and DS2, respectively) and single support (SS) phases on the paretic and non-paretic sides during gait using surface electromyography. Simultaneously, three-dimensional motion analysis was performed to measure the peak values of the ankle joint angle, moment, and power in the sagittal plane. Ground reaction forces (GRFs) of the anterior and posterior components and centers of pressure (COPs) trajectory ranges and velocities were also measured. RESULTS: The CoI during the SS phase on the paretic side was negatively related to ankle dorsiflexion angle, ankle plantarflexion moment, ankle joint power generation, and COP velocity on the paretic side. Furthermore, the CoI during the DS2 phase on both sides was negatively related to anterior GRF amplitude on each side. CONCLUSION: Increased ankle muscle coactivation is related to decreased ankle joint movement during the SS phase on the paretic side to enhance joint stiffness and compensate for stance limb instability, which may be useful for patients who have paretic instability during the stance phase after stroke. PMID- 27189651 TI - RNA interference-mediated knockdown of the Halloween gene Spookiest (CYP307B1) impedes adult eclosion in the western tarnished plant bug, Lygus hesperus. AB - Ecdysteroids play a critical role in coordinating insect growth, development and reproduction. A suite of cytochrome P450 monooxygenases coded by what are collectively termed Halloween genes mediate ecdysteroid biosynthesis. In this study, we describe cloning and RNA interference (RNAi)-mediated knockdown of the CYP307B1 Halloween gene (Spookiest) in the western tarnished plant bug, Lygus hesperus. Transcripts for Ly. hesperus Spookiest (LhSpot) were amplified from all life stages and correlated well with timing of the pre-moult ecdysteroid pulse. In adults, LhSpot was amplified from heads of both genders as well as female reproductive tissues. Heterologous expression of a LhSpot fluorescent chimera in cultured insect cells co-localized with a fluorescent marker of the endoplasmic reticulum/secretory pathway. RNAi-mediated knockdown of LhSpot in fifth instars reduced expression of ecdysone-responsive genes E74 and E75, and prevented adult development. This developmental defect was rescued following application of exogenous 20-hydroxyecdysone but not exogenous 7-dehydrocholesterol. The unequivocal RNAi effects on Ly. hesperus development and the phenotypic rescue by 20-hydroxyecdysone are causal proof of the involvement of LhSpot in ecdysteroid biosynthesis and related developmental processes, and may provide an avenue for development of new control measures against Ly. hesperus. PMID- 27189653 TI - Electrochemical activity and high ionic conductivity of lithium copper pyroborate Li6CuB4O10. AB - In the search for new cathode materials for Li-ion batteries, borate (BO3(3-)) based compounds have gained much interest during the last two decades due to the low molecular weight of the borate polyanions which leads to active materials with increased theoretical capacities. In this context we herein report the electrochemical activity versus lithium and the ionic conductivity of a diborate or pyroborate B2O5(4-) based compound, Li6CuB4O10. By combining various electrochemical techniques with in situ X-ray diffraction, we show that this material can reversibly insert/deinsert limited amounts of lithium (~0.3 Li(+)) in a potential window ranging from 2.5 to 4.5 V vs. Li(+)/Li(0). We demonstrate, via electron paramagnetic resonance (EPR), that such an electrochemical activity centered near 4.25 V vs. Li(+)/Li(0) is associated with the Cu(3+)/Cu(2+) redox couple, confirmed by density functional theory (DFT) calculations. Another specificity of this compound lies in its different electrochemical behavior when cycled down to 1 V vs. Li(+)/Li(0) which leads to the extrusion of elemental copper via a conversion type reaction as deduced by transmission electron microscopy (TEM). Lastly, we probe the ionic conductivity by means of AC and DC impedance measurements as a function of temperature and show that Li6CuB4O10 undergoes a reversible structural transition around 350 degrees C, leading to a surprisingly high ionic conductivity of ~1.4 mS cm(-1) at 500 degrees C. PMID- 27189652 TI - Multiple response optimization of the coagulation process for upgrading the quality of effluent from municipal wastewater treatment plant. AB - To meet the high quality standard of receiving water, the coagulation process using polyferric chloride (PFC) was used to further improve the water quality of effluent from wastewater treatment plants. Uniform design (UD) coupled with response surface methodology (RSM) was adopted to assess the effects of the main influence factors: coagulant dosage, pH and basicity, on the removal of total organic carbon (TOC), NH4(+)-N and PO4(3-)-P. A desirability function approach was used to effectively optimize the coagulation process for the comprehensive removal of TOC, NH4(+)-N and PO4(3-)-P to upgrade the effluent quality in practical application. The optimized operating conditions were: dosage 28 mg/L, pH 8.5 and basicity 0.001. The corresponding removal efficiencies for TOC, NH4(+) N and PO4(3-)-P were 77.2%, 94.6% and 20.8%, respectively. More importantly, the effluent quality could upgrade to surface water Class V of China through coagulation under optimal region. In addition, grey relational analysis (GRA) prioritized these three factors as: pH > basicity > dosage (for TOC), basicity > dosage > pH (for NH4(+)-N), pH > dosage > basicity (for PO4(3-)-P), which would help identify the most important factor to control the treatment efficiency of various effluent quality indexes by PFC coagulation. PMID- 27189654 TI - Curved muscles in biomechanical models of the spine: a systematic literature review. AB - Early biomechanical spine models represented the trunk muscles as straight-line approximations. Later models have endeavoured to accurately represent muscle curvature around the torso. However, only a few studies have systematically examined various techniques and the logic underlying curved muscle models. The objective of this review was to systematically categorise curved muscle representation techniques and compare the underlying logic in biomechanical models of the spine. Thirty-five studies met our selection criteria. The most common technique of curved muscle path was the 'via-point' method. Curved muscle geometry was commonly developed from MRI/CT database and cadaveric dissections, and optimisation/inverse dynamics models were typically used to estimate muscle forces. Several models have attempted to validate their results by comparing their approach with previous studies, but it could not validate of specific tasks. For future needs, personalised muscle geometry, and person- or task specific validation of curved muscle models would be necessary to improve model fidelity. Practitioner Summary: The logic underlying the curved muscle representations in spine models is still poorly understood. This literature review systematically categorised different approaches and evaluated their underlying logic. The findings could direct future development of curved muscle models to have a better understanding of the biomechanical causal pathways of spine disorders. PMID- 27189656 TI - The potential impact of local excision for T1 colonic cancer in elderly and comorbid populations: a decision analysis. AB - BACKGROUND: Population-based bowel cancer screening has resulted in increasing numbers of patients with T1 colonic cancer. The need for colectomy in this group is questioned due to the low risk of lymphatic spread and increased treatment morbidity, particularly for elderly, comorbid patients. This study examined the quality-of-life benefits and risks of endoscopic resection compared with results after colectomy, for low-risk and high-risk T1 colonic cancer. METHODS: Decision analysis using a Markov simulation model was performed; patients were managed with either endoscopic resection (advanced therapeutic endoscopy) or colectomy. Lesions were considered high risk according to accepted national guidelines. Probabilities and utilities (perception of quality of life) were derived from published data. Hypothetical cohorts of 65- and 80-year-old, fit and unfit patients with low-risk or high-risk T1 colonic cancer were studied. The primary outcome was quality-adjusted life expectancy (QALE) in life-years (QALYs). RESULTS: In low-risk T1 colonic neoplasia, endoscopic resection increases QALE by 0.09 QALYS for fit 65-year-olds and by 0.67 for unfit 80-year-olds. For high-risk T1 cancers, the QALE benefit for surgical resection is 0.24 QALYs for fit 65-year olds and the endoscopic QALE benefit is 0.47 for unfit 80-year-olds. The model findings only favored surgery with high local recurrence rates and when quality of life under surveillance was perceived poorly. CONCLUSIONS: Under broad assumptions, endoscopic resection is a reasonable treatment option for both low risk and high-risk T1 colonic cancer, particularly in elderly, comorbid patients. Exploration of methods to facilitate endoscopic resection of T1 colonic neoplasia appears warranted. PMID- 27189657 TI - A lower dose of fluorescein sodium is more suitable for confocal laser endomicroscopy: a feasibility study. AB - BACKGROUND AND AIMS: Image quality can be guaranteed with the conventional dosage of fluorescein sodium in probe-based confocal laser endomicroscopy (pCLE). However, yellow discoloration of the skin seriously affects daily life and simultaneously increases the risk of adverse events such as allergic reactions. The aim of this study was to test whether a lower dosage of fluorescein sodium can provide satisfactory image quality and to compare the diagnostic accuracy of gastric intestinal metaplasia (GIM) through a randomized blind controlled trial. METHODS: Consecutive patients were randomly assigned to different doses of fluorescein sodium. Image quality was determined by the endoscopists' subjective assessments and signal-to-noise ratio (SNR) assessment systems. Skin discoloration was tested using a neonatal transcutaneous jaundice detector. In addition, consecutive patients with a known or suspected diagnosis of GIM were examined by pCLE with the lower dose and the traditional dose. RESULTS: Only 0.01 mL/kg dose of 10% fluorescein sodium led to a significant decrease in image quality (P < .05), and a dose of 0.02 mL/kg had the highest SNR value (P < .05). There were no significant differences in skin discoloration between the 0.01 mL/kg and 0.02 mL/kg doses (P = .148) and no statistical difference in the diagnostic accuracy of pCLE for GIM between the 0.02 mL/kg and 0.10 mL/kg doses (P > .05). The kappa values for the correlation between pCLE and histopathology were 0.867 (95% confidence interval, 0.782-0.952) and 0.891 (95% confidence interval, 0.811-0.971). CONCLUSIONS: The 0.02 mL/kg dose of 10% fluorescein sodium seems to be the best dose for pCLE in the upper GI tract, with comparable image quality with the conventional dose and insignificant skin discoloration. This dose is also very efficient for the diagnosis of GIM. PMID- 27189658 TI - Factors predicting adverse events associated with therapeutic colonoscopy for colorectal neoplasia: a retrospective nationwide study in Japan. AB - BACKGROUND AND AIMS: Few large studies have evaluated the adverse events associated with therapeutic colonoscopy for colorectal neoplasia, including bleeding and bowel perforation. Our aim was to investigate factors associated with these events, using a Japanese national inpatient database. METHODS: We extracted data from the nationwide Japan Diagnosis Procedure Combination database for patients who underwent therapeutic colonoscopy for colorectal neoplasia between 2013 and 2014. Therapeutic colonoscopy included endoscopic submucosal dissection (ESD), EMR, and polypectomy. Outcomes included bleeding, perforation, cerebro-cardiovascular events, and in-hospital death. A multivariable logistic regression model was used to evaluate factors associated with bleeding and bowel perforation. RESULTS: We analyzed 345,546 patients, including 16,812 (4.9%) who underwent ESD, 219,848 (63.6%) who underwent EMR, and 108,886 (31.5%) who underwent polypectomy. The rates of bleeding, bowel perforation, cardiovascular events, cerebrovascular events, and death were 32.5, 0.47, 0.05, 0.88, and 1.32 per 1000 patients, respectively. In the multivariate analysis, a higher bleeding rate was associated with being male, comorbid diseases, ESD, tumor size >=2 cm, and use of drugs including low-dose aspirin, thienopyridines, non-aspirin antiplatelet drugs, novel oral anticoagulants, warfarin, non-steroidal anti inflammatory drugs (NSAIDs), and steroids. A higher bowel perforation rate was associated with being male, renal disease, ESD, tumor size >=2 cm, and drugs including warfarin, NSAIDs, and steroids. CONCLUSIONS: Although the incidence of adverse events after therapeutic colonoscopy was low, several patient-related factors were significantly associated with bleeding and bowel perforation. PMID- 27189659 TI - Enhanced instructions improve the quality of bowel preparation for colonoscopy: a meta-analysis of randomized controlled trials. AB - BACKGROUND AND AIMS: The success of a colonoscopy is highly dependent on the quality of bowel preparation (BP). Many patients have poor BP due to non compliance with regular instructions. Reports concerning the effects of enhanced instructions on BP quality are inconsistent. The aim of this meta-analysis was to compare BP quality between patients receiving enhanced instructions in addition to regular instructions and those who received regular instructions only. METHODS: MEDLINE, EMBASE, Web of Science, and the Cochrane Library were searched to identify relevant studies published for August 2015. The quality of BP (adequate/inadequate), adenoma detection rate, polyp detection rate, willingness to repeat preparation, and adverse events were estimated by using odds ratios (OR) and 95% confidence intervals (CI) with random effects models. RESULTS: Eight randomized controlled trials (n = 3795) were included. Patients who received enhanced instructions showed significantly better BP quality than those receiving only regular instructions (OR, 2.35; 95% CI, 1.65-3.35; P < .001). Subgroup analysis showed that the beneficial effects of enhanced instructions on BP quality were consistent among patients receiving different purgative types, administration methods, or diet restriction (all P < .05). Patients in the enhanced instructions group showed more willingness to repeat the preparation (OR, 1.91; 95% CI, 1.20-3.04; P = .006). CONCLUSIONS: Enhanced instructions significantly improved the quality of BP and willingness to repeat the preparation in patients undergoing colonoscopy. Factors related to patient instructions appear to be as important as the preparation method itself in improving BP quality. PMID- 27189660 TI - Extended endoscopic mucosal resection does not reduce recurrence compared with standard endoscopic mucosal resection of large laterally spreading colorectal lesions. AB - BACKGROUND AND AIMS: Effective interventions to prevent residual and/or recurrent adenoma (RRA) after EMR of large sessile and laterally spreading colorectal lesions (LSL) are yet to be determined. RRA may occur due to inconspicuous adenoma at the EMR margin. We aimed to determine the efficacy and safety of extended EMR (X-EMR) compared with standard EMR (S-EMR). METHODS: A single-center post hoc analysis of LSL >=20 mm referred for treatment was performed. S-EMR was the standard sequential inject and resect method including a 1-mm to 2-mm margin of normal mucosa around the lesion. With X-EMR, at least a 5-mm margin of normal mucosa was excised. Patient and lesion characteristics and procedural outcomes were recorded. The primary endpoint was RRA at first surveillance colonoscopy at 4 months. RESULTS: Between January 2009 and May 2011, 471 lesions (mean size, 37.9 mm) in 424 patients were resected by S-EMR, and between January 2012 and December 2013, 448 lesions (mean size, 39.1 mm) in 396 patients were resected by X-EMR. Resection was successful in 92.3% and 92.6% of referred lesions in the S EMR and X-EMR groups, respectively (P = .978). X-EMR was independently associated with a higher risk of intraprocedural bleeding (IPB) (odds ratio, 3.1; 95% confidence interval [CI], 2.0-5.0; P < .001) but not other adverse events. RRA was present in 39 of 333 patients (11.7%) and 30 of 296 patients (10.1%) in the S EMR and X-EMR groups, respectively (P = .15). X-EMR was not related to recurrence (hazard ratio, 0.8; 95% CI, 0.5-1.3; P = .399). CONCLUSIONS: X-EMR does not reduce RRA and increases the risk of IPB compared with S-EMR. Alternative methods for the prevention of RRA are required. PMID- 27189655 TI - Spina bifida. AB - Spina bifida is a birth defect in which the vertebral column is open, often with spinal cord involvement. The most clinically significant subtype is myelomeningocele (open spina bifida), which is a condition characterized by failure of the lumbosacral spinal neural tube to close during embryonic development. The exposed neural tissue degenerates in utero, resulting in neurological deficit that varies with the level of the lesion. Occurring in approximately 1 per 1,000 births worldwide, myelomeningocele is one of the most common congenital malformations, but its cause is largely unknown. The genetic component is estimated at 60-70%, but few causative genes have been identified to date, despite much information from mouse models. Non-genetic maternal risk factors include reduced folate intake, anticonvulsant therapy, diabetes mellitus and obesity. Primary prevention by periconceptional supplementation with folic acid has been demonstrated in clinical trials, leading to food fortification programmes in many countries. Prenatal diagnosis is achieved by ultrasonography, enabling women to seek termination of pregnancy. Individuals who survive to birth have their lesions closed surgically, with subsequent management of associated defects, including the Chiari II brain malformation, hydrocephalus, and urological and orthopaedic sequelae. Fetal surgical repair of myelomeningocele has been associated with improved early neurological outcome compared with postnatal operation. Myelomeningocele affects quality of life during childhood, adolescence and adulthood, posing a challenge for individuals, families and society as a whole. For an illustrated summary of this Primer, visit: http://go.nature.com/fK9XNa. PMID- 27189662 TI - Oligoantiemesis or Inadequate Prescription of Antiemetics in the Emergency Department: A Local and National Perspective. AB - BACKGROUND: Nausea and vomiting are common, but prevalence of antiemetic use in ED patients is unknown. OBJECTIVES: We determined the use of antiemetics in emergency department (ED) patients presenting with nausea and vomiting (NV). METHODS: We conducted a retrospective chart review of ED patients presenting to a local ED with NV and analyzed data from the National Hospital Ambulatory Care Survey for similar patients to determine the frequency of administration of antiemetics in the ED. RESULTS: Of 3876 patients presenting to a local ED with NV in 2014, 2637 (68% [95% confidence interval (CI) 67-69%]) received an antiemetic. Of an estimated 11.3 million U.S. ED visits for NV in 2011 (the latest year available), antiemetics were prescribed in 56% (95% CI 53-59%). Females, older patients, and those with vomiting were more likely to receive antiemetics. Use of antiemetics was associated with reduced admissions in the single institution (odds ratio [OR] 0.62, 95% CI 0.52-0.74), but not in the national database (OR 1.08, 95% CI 0.74-1.60). CONCLUSIONS: Many patients presenting with NV do not receive antiemetics while in the ED. Effort should be made to further study and reduce the phenomenon of undertreatment of nausea or vomiting, coined "oligoantiemesis." PMID- 27189661 TI - Alternating Diet as a Preventive and Therapeutic Intervention for High Fat Diet induced Metabolic Disorder. AB - This study presents the alternating diet as a new strategy in combating obesity and metabolic diseases. Lean or obese mice were fed a high-fat diet (HFD) for five days and switched to a regular diet for one (5 + 1), two (5 + 2), or five (5 + 5) days before switching back to HFD to start the second cycle, for a total of eight weeks (for prevention) or five weeks (for treatment) without limiting animals' access to food. Our results showed that animals with 5 + 2 and 5 + 5 diet alternations significantly inhibited body weight and fat mass gain compared to animals fed an HFD continuously. The dietary switch changed the pattern of daily caloric intake and suppressed HFD-induced adipose macrophage infiltration and chronic inflammation, resulting in improved insulin sensitivity and alleviated fatty liver. Alternating diet inhibited HFD-induced hepatic Ppargamma mediated lipid accumulation and activated the expression of Pparalpha and its target genes. Alternating diet in the 5 + 5 schedule induced weight loss in obese mice and reversed the progression of metabolic disorders, including hepatic steatosis, glucose intolerance, and inflammation. The results provide direct evidence to support that alternating diet represents a new intervention in dealing with the prevalence of diet-induced obesity. PMID- 27189663 TI - Identification of the STEMI-equivalent de Winter Electrocardiogram Pattern After Ventricular Fibrillation Cardiac Arrest: A Case Report. AB - BACKGROUND: Patients with chest pain who have ST elevations on electrocardiogram (ECG) are at high risk for ST-elevation myocardial infarction (STEMI). Recent literature has reported various STEMI equivalents, which may be equally threatening. One STEMI equivalent, previously named the de Winter pattern, describes ECG changes where there are ST-segment depressions in the precordial leads in association with tall, symmetrical, hyperacute T-waves. These changes have been connected with proximal left anterior descending coronary artery occlusion. CASE REPORT: We have identified a case of the de Winter ECG pattern immediately after ventricular fibrillation cardiac arrest. A 33-year-old man presented with waxing and waning severe substernal chest pain. The patient was on no prior medications, and had no risk factors for acute coronary syndrome. The initial ECG showed ST depression, which was followed by normalization in a repeat ECG only minutes later. The patient then developed ventricular fibrillation cardiac arrest. After defibrillation, return of spontaneous circulation was achieved and subsequent ECGs demonstrated the de Winter ECG pattern. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The characteristic ECG changes within the de Winter ECG pattern may be missed or misdiagnosed as nonspecific, reversible ischemia. This can significantly lengthen the transportation to a center equipped with a percutaneous coronary intervention laboratory, and thus the start of reperfusion therapy. It is imperative that all practitioners learn to identify this novel ECG pattern as a STEMI equivalent to ensure appropriate intervention in the cardiac catheterization laboratory. PMID- 27189664 TI - Ultrasonography for diagnosis and follow-up of carpal tunnel syndrome in mucopolysaccharidosis. PMID- 27189665 TI - Ethics: the perfect mix? Response to Buetow. AB - This is a response to Stephen Buetow's comments on our paper 'Collectivity, evil and the dynamics of moral value'. PMID- 27189666 TI - Epithelial-mesenchymal-transition regulators in prostate cancer: Androgens and beyond. AB - Castration resistant prostate cancer (CRPC) remains one of the leading causes of cancer deaths among men. Conventional therapies targeting androgen signaling driven tumor growth have provided limited survival benefit in patients. Recent identification of the critical molecular and cellular events surrounding tumor progression, invasion, and metastasis to the bone as well as other sites provide new insights in targeting advanced disease. Epithelial mesenchymal transition (EMT) is a process via which epithelial cells undergo morphological changes to a motile mesenchymal phenotype, a phenomenon implicated in cancer metastasis but also therapeutic resistance. Therapeutic targeting of EMT has the potential to open a new avenue in the treatment paradigm of CRPC through the reversion of the invasive mesenchymal phenotype to the well differentiated tumor epithelial tumor phenotype. Overcoming therapeutic resistance in metastatic prostate cancer is an unmet need in today's clinical management of advanced disease. This review outlines our current understanding of the contribution of EMT and its reversal to MET in prostate cancer progression and therapeutic resistance, and the impact of selected targeting of mechanisms of resistance via EMT towards a therapeutic benefit in patients with CRPC. PMID- 27189667 TI - Direct imaging of molecular symmetry by coherent anti-stokes Raman scattering. AB - Nonlinear optical methods, such as coherent anti-Stokes Raman scattering and stimulated Raman scattering, are able to perform label-free imaging, with chemical bonds specificity. Here we demonstrate that the use of circularly polarized light allows to retrieve not only the chemical nature but also the symmetry of the probed sample, in a single measurement. Our symmetry-resolved scheme offers simple access to the local organization of vibrational bonds and as a result provides enhanced image contrast for anisotropic samples, as well as an improved chemical selectivity. We quantify the local organization of vibrational bonds on crystalline and biological samples, thus providing information not accessible by spontaneous Raman and stimulated Raman scattering techniques. This work stands for a symmetry-resolved contrast in vibrational microscopy, with potential application in biological diagnostic. PMID- 27189669 TI - Dispelling some myths about the CO2 solubility in ionic liquids. AB - Ionic liquids have been objects of extensive research for physical sorption of CO2 and a number of myths have been perpetuated in the literature, for lack of a critical analysis, concerning their potential for CO2 capture. This study carries a critical analysis of a number of widely accepted ideas and others not so well accepted that have been repeatedly expressed in the literature concerning the CO2 physical sorption in ionic liquids. Using the CO2 solubility in eicosane as benchmark, it will be shown that there is no evidence that ILs display a physical sorption of CO2 larger than n-alkanes when analyzed in adequate concentration units; the fluorination of the ions has no impact on the CO2 solubility and the oxygenation will marginally contribute to a decrease of the solubility. Ionic liquid-based deep eutectic systems are also shown to have a poor CO2 solubility. Although these widely used approaches to physically enhance the CO2 solubility in ILs do not seem to have any positive influence, this does not mean that other types of interaction cannot provide enhanced CO2 solubility as in the case of the anion [B(CN)4] confirmed here by a critical analysis of the published data. The mechanism of CO2 physical sorption in ionic liquids is discussed based on the results analyzed, supported by spectroscopic measurements and molecular simulations previously reported and further suggestions of possibilities for enhanced physical sorption based on fluorinated aromatic rings, other cyano based anions, mixtures with other ILs or solvents or the use of porous liquids are proposed. PMID- 27189668 TI - Asthma. AB - Asthma is the most common inflammatory disease of the lungs. The prevalence of asthma is increasing in many parts of the world that have adopted aspects of the Western lifestyle, and the disease poses a substantial global health and economic burden. Asthma involves both the large-conducting and the small-conducting airways, and is characterized by a combination of inflammation and structural remodelling that might begin in utero. Disease progression occurs in the context of a developmental background in which the postnatal acquisition of asthma is strongly linked with allergic sensitization. Most asthma cases follow a variable course, involving viral-induced wheezing and allergen sensitization, that is associated with various underlying mechanisms (or endotypes) that can differ between individuals. Each set of endotypes, in turn, produces specific asthma characteristics that evolve across the lifecourse of the patient. Strong genetic and environmental drivers of asthma interconnect through novel epigenetic mechanisms that operate prenatally and throughout childhood. Asthma can spontaneously remit or begin de novo in adulthood, and the factors that lead to the emergence and regression of asthma, irrespective of age, are poorly understood. Nonetheless, there is mounting evidence that supports a primary role for structural changes in the airways with asthma acquisition, on which altered innate immune mechanisms and microbiota interactions are superimposed. On the basis of the identification of new causative pathways, the subphenotyping of asthma across the lifecourse of patients is paving the way for more-personalized and precise pathway-specific approaches for the prevention and treatment of asthma, creating the real possibility of total prevention and cure for this chronic inflammatory disease. PMID- 27189671 TI - Modeling the fluid-dynamics and oxygen consumption in a porous scaffold stimulated by cyclic squeeze pressure. AB - The architecture and dynamic physical environment of tissues can be recreated in vitro by combining 3D porous scaffolds and bioreactors able to apply controlled mechanical stimuli on cells. In such systems, the entity of the stimuli and the distribution of nutrients within the engineered construct depend on the micro structure of the scaffolds. In this work, we present a new approach for optimizing computational fluid-dynamics (CFD) models for the investigation of fluid-induced forces generated by cyclic squeeze pressure within a porous construct, coupled with oxygen consumption of cardiomyocytes. A 2D axial symmetric macro-scaled model of a squeeze pressure bioreactor chamber was used as starting point for generating time dependent pressure profiles. Subsequently the fluid movement generated by the pressure fields was coupled with a complete 3D micro-scaled model of a porous protein cryogel. Oxygen transport and consumption inside the scaffold was evaluated considering a homogeneous distribution of cardiomyocytes throughout the structure, as confirmed by preliminary cell culture experiments. The results show that a 3D description of the system, coupling a porous geometry and time dependent pressure driven flow with fluid-structure interaction provides an accurate and meaningful description of the microenvironment in terms of shear stress and oxygen distribution than simple stationary 2D models. PMID- 27189670 TI - Assessing mutant p53 in primary high-grade serous ovarian cancer using immunohistochemistry and massively parallel sequencing. AB - The tumour suppressor p53 is mutated in cancer, including over 96% of high-grade serous ovarian cancer (HGSOC). Mutations cause loss of wild-type p53 function due to either gain of abnormal function of mutant p53 (mutp53), or absent to low mutp53. Massively parallel sequencing (MPS) enables increased accuracy of detection of somatic variants in heterogeneous tumours. We used MPS and immunohistochemistry (IHC) to characterise HGSOCs for TP53 mutation and p53 expression. TP53 mutation was identified in 94% (68/72) of HGSOCs, 62% of which were missense. Missense mutations demonstrated high p53 by IHC, as did 35% (9/26) of non-missense mutations. Low p53 was seen by IHC in 62% of HGSOC associated with non-missense mutations. Most wild-type TP53 tumours (75%, 6/8) displayed intermediate p53 levels. The overall sensitivity of detecting a TP53 mutation based on classification as 'Low', 'Intermediate' or 'High' for p53 IHC was 99%, with a specificity of 75%. We suggest p53 IHC can be used as a surrogate marker of TP53 mutation in HGSOC; however, this will result in misclassification of a proportion of TP53 wild-type and mutant tumours. Therapeutic targeting of mutp53 will require knowledge of both TP53 mutations and mutp53 expression. PMID- 27189673 TI - Predictors of full-time faculty appointment among MD-PhD program graduates: a national cohort study. AB - PURPOSE: The authors sought to identify variables associated with MD-PhD program graduates' academic medicine careers. METHODS: We analyzed data for a national cohort of MD-PhD program graduates from 2000 to 2005, using multivariable logistic regression to identify independent predictors of full-time academic medicine faculty appointment through 2013. RESULTS: Of 1,860 MD-PhD program graduates in 2000-2005, we included 1,846 (99.2%) who had completed residency training before 2014. Of these 1,846 graduates, 968 (52.4%) held full-time faculty appointments. Graduates who attended schools with Medical Scientist Training Program (MSTP) funding (vs. no MSTP funding; adjusted odds ratio [aOR], 1.41; 95% confidence interval [CI], 1.14-1.74) and participated in >=1 year of research during residency (vs. no documented research year; aOR, 1.85; 95% CI, 1.50-2.28) were more likely to have held full-time faculty appointments. Asian/Pacific Islander (aOR, 0.74; 95% CI, 0.60-0.93) and under-represented minority (URM; aOR, 0.68; 95% CI, 0.48-0.98) graduates (each vs. white graduates), graduates who reported total debt of >=$100,000 (vs. no debt) at graduation (aOR, 0.58; 95% CI, 0.39-0.88), and graduates in surgical practice (aOR, 0.64; 95% CI, 0.48-0.84) and other practice (aOR, 0.66, 95% CI, 0.54-0.81) specialties (each vs. 'medicine, pediatrics, pathology, or neurology') were less likely to have held full-time faculty appointments. Gender was not independently associated with likelihood of full-time faculty appointment. CONCLUSIONS: Over half of all MD-PhD program graduates in our study had full-time faculty appointments. Our findings regarding variables independently associated with full time faculty appointments can inform the design of strategies to promote academic medicine career choice among MD-PhD program graduates. Further research is warranted to identify other factors amenable to intervention, in addition to those included in our study, which will foster the further development of a diverse academic medicine physician-scientist workforce nationally. PMID- 27189672 TI - Utility-based designs for randomized comparative trials with categorical outcomes. AB - A general utility-based testing methodology for design and conduct of randomized comparative clinical trials with categorical outcomes is presented. Numerical utilities of all elementary events are elicited to quantify their desirabilities. These numerical values are used to map the categorical outcome probability vector of each treatment to a mean utility, which is used as a one-dimensional criterion for constructing comparative tests. Bayesian tests are presented, including fixed sample and group sequential procedures, assuming Dirichlet-multinomial models for the priors and likelihoods. Guidelines are provided for establishing priors, eliciting utilities, and specifying hypotheses. Efficient posterior computation is discussed, and algorithms are provided for jointly calibrating test cutoffs and sample size to control overall type I error and achieve specified power. Asymptotic approximations for the power curve are used to initialize the algorithms. The methodology is applied to re-design a completed trial that compared two chemotherapy regimens for chronic lymphocytic leukemia, in which an ordinal efficacy outcome was dichotomized, and toxicity was ignored to construct the trial's design. The Bayesian tests also are illustrated by several types of categorical outcomes arising in common clinical settings. Freely available computer software for implementation is provided. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27189674 TI - RETRACTED: Design, synthesis, structure-activity relationship and kinase inhibitory activity of substituted 3-methyl-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin 4-ones. AB - This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy).This article has been retracted at the request of the author who confirmed that the purity of some of the described compounds is below acceptable standards and thus the biochemical results reported in the paper have no validity. PMID- 27189675 TI - The SAR of brain penetration for a series of heteroaryl urea FAAH inhibitors. AB - The SAR of brain penetration for a series of heteroaryl piperazinyl- and piperadinyl-urea fatty acid amide hydrolase (FAAH) inhibitors is described. Brain/plasma (B/P) ratios ranging from >4:1 to as low as 0.02:1 were obtained through relatively simple structural changes to various regions of the heteroaryl urea scaffold. It was not possible to predict the degree of central nervous system (CNS) penetration from the volumes of distribution (Vd) obtained from pharmacokinetic (PK) experiments as very high Vds did not correlate with high B/P ratios. Similarly, calculated topological polar surface areas (TPSAs) did not consistently correlate with the degree of brain penetration. The lowest B/P ratios were observed for those compounds that were significantly ionized at physiological pH. However, as this class of compounds inhibits the FAAH enzyme through covalent modification, low B/P ratios did not preclude effective central target engagement. PMID- 27189677 TI - Structural effect of glyme-Li(+) salt solvate ionic liquids on the conformation of poly(ethylene oxide). AB - The conformation of 36 kDa polyethylene oxide (PEO) dissolved in three glyme Li(+) solvate ionic liquids (SILs) has been investigated by small angle neutron scattering (SANS) and rheology as a function of concentration and compared to a previously studied SIL. The solvent quality of a SIL for PEO can be tuned by changing the glyme length and anion type. Thermogravimetric analysis (TGA) reveals that PEO is dissolved in the SILs through Li(+)-PEO coordinate bonds. All SILs (lithium triglyme bis(trifluoromethanesulfonyl)imide ([Li(G3)]TFSI), lithium tetraglyme bis(pentafluoroethanesulfonyl)imide ([Li(G4)]BETI), lithium tetraglyme perchlorate ([Li(G4)]ClO4) and the recently published [Li(G4)]TFSI) are found to be moderately good solvents for PEO but solvent quality decreases in the order [Li(G4)]TFSI ~ [Li(G4)]BETI > [Li(G4)]ClO4 > [Li(G3)]TFSI due to decreased availability of Li(+) for PEO coordination. For the same glyme length, the solvent qualities of SILs with TFSI(-) and BETI(-) anions ([Li(G4)]TFSI and [Li(G4)]BETI) are very similar because they weakly coordinate with Li(+), which facilitates Li(+)-PEO interactions. [Li(G4)]ClO4 presents a poorer solvent environment for PEO than [Li(G4)]BETI because ClO4(-) binds more strongly to Li(+) and thereby hinders interactions with PEO. [Li(G3)]TFSI is the poorest PEO solvent of these SILs because G3 binds more strongly to Li(+) than G4. Rheological and radius of gyration (Rg) data as a function of PEO concentration show that the PEO overlap concentrations, c* and c**, are similar in the three SILs. PMID- 27189676 TI - Steroids from the rhizome of Anemarrhena asphodeloides and their cytotoxic activities. AB - Cancer remains a major killer worldwide. To search for novel naturally occurring compounds that are cytotoxic to cancer cells to be used as lead structures for drug development, five new steroids (1-5) along with seven known ones (6-12) were isolated from the rhizome of Anemarrhena asphodeloides Bge. Their structures were established by detailed spectral studies, including 1D-NMR, 2D-NMR, HR-ESI-MS and by comparison with literature data. These compounds exhibited different levels of growth inhibition against A549, HepG2, Hep3B, Bcap37 and MCF7 cell lines in vitro. Compounds 9, 10 and 11 showed potent inhibitory against all the tested cell lines with IC50 values ranging from 0.35+/-0.15 to 25.53+/-0.31MUM. The three compounds displayed stronger inhibitory activities against A549, HepG2 and Hep3B cell lines compared with the positive control 5-fluorouracil. The experimental data obtained permit us to identify the roles of the sugar moieties, hydroxyl group, double bond and F-ring with regard to their cytotoxic activities. PMID- 27189678 TI - Lung Ultrasound for Diagnosing Pneumothorax in the Critically Ill Neonate. AB - OBJECTIVES: To evaluate the accuracy of lung ultrasound for the diagnosis of pneumothorax in the sudden decompensating patient. STUDY DESIGN: In an international, prospective study, sudden decompensation was defined as a prolonged significant desaturation (oxygen saturation <65% for more than 40 seconds) and bradycardia or sudden increase of oxygen requirement by at least 50% in less than 10 minutes with a final fraction of inspired oxygen >=0.7 to keep stable saturations. All eligible patients had an ultrasound scan before undergoing a chest radiograph, which was the reference standard. RESULTS: Forty two infants (birth weight = 1531 +/- 812 g; gestational age = 31 +/- 3.5 weeks) were enrolled in 6 centers; pneumothorax was detected in 26 (62%). Lung ultrasound accuracy in diagnosing pneumothorax was as follows: sensitivity 100%, specificity 100%, positive predictive value 100%, and negative predictive value 100%. Clinical evaluation of pneumothorax showed sensitivity 84%, specificity 56%, positive predictive value 76%, and negative predictive value 69%. After sudden decompensation, a lung ultrasound scan was performed in an average time of 5.3 +/- 5.6 minutes vs 19 +/- 11.7 minutes required for a chest radiography. Emergency drainage was performed after an ultrasound scan but before radiography in 9 cases. CONCLUSIONS: Lung ultrasound shows high accuracy in detecting pneumothorax in the critical infant, outperforming clinical evaluation and reducing time to imaging diagnosis and drainage. PMID- 27189679 TI - Effects of Perinatal Dioxin Exposure on Development of Children during the First 3 Years of Life. AB - OBJECTIVE: To investigate the longitudinal effects of perinatal exposure to dioxin on neurodevelopment and physical growth of a birth cohort during the first 3 years of life. STUDY DESIGN: A total of 217 mother-infant pairs living in a dioxin-contaminated area in Vietnam were followed up. Perinatal dioxin exposure of infants was estimated by the measurement of dioxin levels in breast milk of nursing mothers. Neurodevelopment of infants and children, including cognitive, language, and motor development, was determined at 4 months, 1 year, and 3 years of age. Physical growth, including weight, height, and head and abdominal circumferences, was measured at birth, 1 and 4 months, and 1 and 3 years of age. Multivariate mixed models were applied for analyzing repeated measures. RESULTS: In boys, composite motor and gross motor scores were decreased with increasing exposure of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TetraCDD). The high toxic equivalent of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDDs/PCDFs-TEQ) group showed a significant decrease in expressive communication score. In girls, there was no decreased score in any neurodevelopment aspects in high-exposure groups. All body size measures in boys were decreased in the high-exposure groups of 2,3,7,8-TetraCDD and PCDDs/PCDFs TEQ. In girls, high 2,3,7,8-TetraCDD and PCDDs/PCDFs-TEQ exposure was associated with increased head and abdominal circumferences. CONCLUSIONS: Perinatal dioxin exposure affects physical growth and neurodevelopment of infants and children in the first 3 years of life in a sex-specific manner. PMID- 27189680 TI - Admission Hypothermia in Very Preterm Infants and Neonatal Mortality and Morbidity. AB - OBJECTIVE: To investigate the association between body temperature at admission to neonatal intensive care and in-hospital mortality in very preterm infants, stratified by postnatal age of death. Moreover, we assessed the association between admission temperature and neonatal morbidity. STUDY DESIGN: In this cohort study from 19 regions in 11 European countries, we measured body temperature at admission for infants admitted for neonatal care after very preterm birth (<32 weeks of gestation; n = 5697) who were followed to discharge or death. Associations between body temperature at admission and in-hospital mortality and neonatal morbidity were analyzed by the use of mixed effects generalized linear models. The final model adjusted for pregnancy complications, singleton or multiple pregnancy, antenatal corticosteroids, mode of delivery, gestational age, infant size and sex, and Apgar score <7 at 5 minutes. RESULTS: A total of 53.4% of the cohort had a body temperature at admission less than 36.5 degrees C, and 12.9% below 35.5 degrees C. In the adjusted model, an admission temperature <35.5 degrees C was associated with increased mortality at postnatal ages 1-6 days, (risk ratio 2.41; 95% CI 1.45-4.00), and 7-28 days (risk ratio 1.79; 1.15-2.78) but not after 28 days of age. We found no associations between admission temperature and neonatal morbidity. CONCLUSION: Admission hypothermia after very preterm birth is a significant problem in Europe, associated with an increased risk of early and late neonatal death. PMID- 27189681 TI - Caffeine for the Treatment of Apnea in Bronchiolitis: A Randomized Trial. AB - OBJECTIVE: To evaluate the efficacy and safety of caffeine citrate in the treatment of apnea in bronchiolitis. STUDY DESIGN: Eligible infants aged <=4 months presenting to the main pediatric emergency service with apnea associated bronchiolitis were stratified by gestational age (<34 weeks or longer) and randomized to receive a single dose of intravenous 25 mg/kg caffeine citrate or saline placebo. The primary efficacy outcome was a 24-hour apnea-free period beginning after completion of the blinded study drug infusion. Secondary outcomes were frequency of apnea by 24, 48, and 72 hours after study medication, need for noninvasive/invasive ventilation, and length of stay in the hospital's pediatric intensive care/step-down unit. RESULTS: A total of 90 infants diagnosed with viral bronchiolitis associated with apnea (median age, 38 days) were enrolled. The rate of respiratory virus panel positivity was similar in the 2 groups (78% for the placebo group vs 84% for the caffeine group). The geometric mean duration to a 24-hour apnea-free period was 28.1 hours (95% CI, 25.6-32.3 hours) for the caffeine group and 29.1 hours (95% CI, 25.7-32.9 hours) for the placebo group (P = .88; OR, 0.99; 95% CI, 0.83-1.17). The frequency of apnea at 24 hours, 24-48 hours, and 48-72 hours after enrollment and the need for noninvasive and invasive ventilation were similar in the 2 groups. No safety issues were reported. CONCLUSIONS: A single dose of caffeine citrate did not significantly reduce apnea episodes associated with bronchiolitis. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01435486. PMID- 27189682 TI - Diagnosis of adrenal insufficiency in eosinophilic esophagitis: The importance of timing of cortisol measurements in interpreting low-dose adrenocorticotropic hormone stimulation testing. PMID- 27189683 TI - Elimination of the Out-of-Pocket Charge for Children's Primary Care Visits: An Application of Value-Based Insurance Design. AB - OBJECTIVE: To evaluate the impact of a value-based insurance design for primary care among children. STUDY DESIGN: A retrospective analysis of health care claims data on 25 950 children (<18 years of age) was conducted. Individuals were enrolled in a large employer's health plans when zero out-of-pocket cost for primary care physician visits was implemented. A rigorous propensity score matching process was used to generate a control group of equal size from a database of other employer-sponsored insurees. Multivariate difference-in differences models estimated the effect of zero out-of-pocket cost on 21 health services and cost outcomes 24 months after intervention. RESULTS: Zero out-of pocket cost for primary care was associated with significant increases (P < .01) in primary care physician visits (+32 per 100 children), as well as decreases in emergency department (-5 per 100 children) and specialist physician visits (-12 per 100 children). The number of prescription drug fills also declined (-20 per 100 children), yet medication adherence for 3 chronic conditions was unaffected. The receipt of well child visits and 4 recommended vaccinations were all significantly (P < .05) greater under the new plan design feature. Employer costs for primary care increased significantly (P < .01) in association with greater utilization ($29 per child), but specialist visit costs declined (-$12 per child) and total health care costs per child did not exhibit a statistically significant increase. CONCLUSION: This novel application of value-based insurance design warrants broader deployment and assessment of its longer term outcomes. As with recommended preventive services, policymakers should consider exempting primary care from health insurance cost-sharing. PMID- 27189684 TI - Can One Predict Resolution of Neonatal Hyperthyrotropinemia? AB - OBJECTIVE: To identify predictors of transience vs permanence of neonatal hyperthyrotropinemia. We hypothesized that infants with greater severity of perinatal stress are more likely to have transient thyrotropin elevations. STUDY DESIGN: We retrospectively studied infants diagnosed with hyperthyrotropinemia between 2002 and 2014, following them for up to 12 years after diagnosis. Patients were divided into 3 groups: transient hyperthyrotropinemia (treatment was never prescribed), transient congenital hypothyroidism (treatment started but discontinued), and permanent congenital hypothyroidism (withdrawal unsuccessful or not attempted). We performed univariate and multiple logistic regression analyses, including and excluding infants with maternal thyroid disease. RESULTS: We included 76 infants, gestational age mean (+/-SD) 34.2 (+/-5.7) weeks, evaluated for hyperthyrotropinemia. Thirty-five (46%) were never treated, and 41 (54%) received levothyroxine. Of the treated patients, 16 successfully discontinued levothyroxine, and for 25 withdrawal either failed or was not attempted. We found that male patients were almost 5 times more likely than female patients to have transient neonatal hyperthyrotropinemia (OR 4.85; 95% CI 1.53-15.37). We documented greater maternal age (31.5 +/- 5.48 years vs 26 +/- 6.76 years, mean +/- SD, P = .02), greater rate of cesarean delivery (86.7% vs 54.2%; P = .036), and retinopathy of prematurity (37.5% vs 8%; P = .02) in the group with transient congenital hypothyroidism vs the group with permanent congenital hypothyroidism. CONCLUSION: The results show transience of neonatal thyrotropin elevations in a majority of patients and suggest a possible association of hyperthyrotropinemia with maternal and perinatal risk factors. PMID- 27189686 TI - Parent and Teacher Perspectives on Emerging Executive Functioning in Preschoolers With Neurofibromatosis Type 1: Comparison to Unaffected Children and Lab-Based Measures. AB - Objective: Children with neurofibromatosis type 1 (NF1) are at risk for executive functioning (EF) challenges, with little research with preschoolers. Methods: EF was examined using parent and teacher ratings of preschool-aged children with NF1 ( n = 26) and parent ratings of unaffected children ( n = 37) on the Behavior Rating Inventory for Executive Functioning-Preschool Form. Relations to performance on laboratory measures were also examined. Results: Based on parent ratings, children with NF1 had more dysfunction than the normative mean on the Working Memory (WM) scale and Emergent Metacognition Index (EMI). Teacher ratings indicated greater dysfunction than the normative mean on the WM and Planning/Organization scales, EMI, and General Executive Composite. Children with NF1 showed more difficulties than unaffected children on the WM scale. Teacher report of WM was significantly correlated with Differential Ability Scales-Second Edition Digits Forward performance. Conclusions: WM emerged as an area of difficulty for young children with NF1. PMID- 27189685 TI - The Impact of Neurodevelopmental and Psychosocial Outcomes on Health-Related Quality of Life in Survivors of Congenital Heart Disease. PMID- 27189687 TI - Better Nights/Better Days-Distance Intervention for Insomnia in School-Aged Children With/Without ADHD: A Randomized Controlled Trial. AB - OBJECTIVE: Better Nights/Better Days, a distance intervention for insomnia in school-aged children (with and without attention-deficit/hyperactivity disorder [ADHD]), was evaluated to determine its effectiveness on children's sleep and psychosocial functioning. METHODS: A single center, parallel group design randomized controlled trial (stratified on ADHD diagnosis) was conducted. Parents were randomized to intervention (n = 31) or waitlist control (n = 30), and completed questionnaires administered over the phone at baseline, postintervention (2 months), and follow-up (6 months). Actigraphy was also collected. The intervention consisted of a five-session manual and weekly telephone coach support. RESULTS: The intervention group demonstrated a significant reduction in sleep problems and improved psychosocial functioning at postintervention and follow-up. Actigraphy results indicated improved sleep onset, but not sleep duration. Children with and without ADHD responded in a similar manner to this intervention. Parents provided high satisfaction ratings. CONCLUSIONS: This intervention holds promise as an accessible, sustainable, and effective program to address insomnia in school-aged children. PMID- 27189689 TI - Topical Review: Mind Your Language-Translation Matters (A Narrative Review of Translation Challenges). AB - OBJECTIVE: Translation of developmental-behavioral screening tools for use worldwide can be daunting. We summarize issues in translating these tools. METHODS: Instead of a theoretical framework of "equivalence" by Pena and International Test Commission guidelines, we decided upon a practical approach used by the American Association of Orthopedic Surgeons (AAOS). We derived vignettes from the Parents' Evaluation of Developmental Status manual and published literature and mapped them to AAOS. RESULTS: We found that a systematic approach to planning and translating developmental-behavioral screeners is essential to ensure "equivalence" and encourage wide consultation with experts. CONCLUSION: Our narrative highlights how translations can result in many challenges and needed revisions to achieve "equivalence" such that the items remain consistent, valid, and meaningful in the new language for use in different cultures. Information sharing across the community of researchers is encouraged. This narrative may be helpful to novice researchers. PMID- 27189691 TI - Daily Bidirectional Relationships Between Sleep and Mental Health Symptoms in Youth With Emotional and Behavioral Problems. AB - OBJECTIVE: The present study examined the daily, bidirectional relationships between sleep and mental health symptoms in youth presenting to mental health treatment. METHODS: Youth aged 6 to 11 (36% female, 44% European American) presenting to outpatient behavioral health treatment (N = 25) were recruited to participate in the study. Children and parents completed daily questionnaires regarding the child's sleep, mood, and behavior for a 14-day period, while youth wore an actigraph watch to objectively measure sleep. RESULTS: Examining between- and within-person variance using multilevel models, results indicate that youth had poor sleep duration and quality and that sleep and mental health symptoms were highly related at the daily level. Between-person effects were found to be most important and significant bidirectional relationships exist. CONCLUSIONS: Identifying and addressing sleep problems in the context of mental health treatment is important, as poor sleep is associated with increased symptomology and may contribute to worsened mental health. PMID- 27189690 TI - Investigating the Role of Hypothalamic Tumor Involvement in Sleep and Cognitive Outcomes Among Children Treated for Craniopharyngioma. AB - OBJECTIVE: Despite excellent survival prognosis, children treated for craniopharyngioma experience significant morbidity. We examined the role of hypothalamic involvement (HI) in excessive daytime sleepiness (EDS) and attention regulation in children enrolled on a Phase II trial of limited surgery and proton therapy. METHODS: Participants completed a sleep evaluation (N = 62) and a continuous performance test (CPT) during functional magnetic resonance imaging (fMRI; n = 29) prior to proton therapy. RESULTS: EDS was identified in 76% of the patients and was significantly related to increased HI extent (p = .04). There was no relationship between CPT performance during fMRI and HI or EDS. Visual examination of group composite fMRI images revealed greater spatial extent of activation in frontal cortical regions in patients with EDS, consistent with a compensatory activation hypothesis. CONCLUSION: Routine screening for sleep problems during therapy is indicated for children with craniopharyngioma, to optimize the timing of interventions and reduce long-term morbidity. PMID- 27189692 TI - Stigma in Medical Settings As Reported Retrospectively by Women With Congenital Adrenal Hyperplasia (CAH) for Their Childhood and Adolescence. AB - Objectives: To perform a qualitative study of stigma experienced in medical settings by children and adolescents with congenital genital ambiguity (CGA). Methods: 62 women with classical congenital adrenal hyperplasia (CAH) of variable severity took part in a qualitative retrospective interview that focused on the impact of CAH and its medical treatment, with an emphasis on childhood and adolescence. Categorization of stigmatization was based on deductive content analysis of the interview transcripts. Results: Many women recalled experiencing the genital examinations in childhood and adolescence as adverse, stigmatizing events, leading to avoidance reactions and self-perception as abnormal, particularly when the examinations included groups of trainees. Some women also experienced as adverse the nonverbal and verbal reactions of individual physicians who were unfamiliar with CGA. Conclusions: Genital examinations constitute salient events for children and adolescents with CGA. They are easily experienced as strongly stigmatizing, especially when combined with teaching. PMID- 27189693 TI - Sleep Problems as Consequence, Contributor, and Comorbidity: Introduction to the Special Issue on Sleep, Published in Coordination With Special Issues in Clinical Practice in Pediatric Psychology and Journal of Developmental and Behavioral Pediatrics. AB - Despite long-standing public and scientific interest in the phenomenon of sleep, the current decade has shown tremendous growth in our understanding of the sleep of children who have medical or developmental conditions. To accommodate, promote, and guide that growth, Journal of Pediatric Psychology, Clinical Practice in Pediatric Psychology, and Journal of Developmental and Behavioral Pediatrics have published coordinated special issues, encompassing >30 relevant articles. This article introduces the special issue in Journal of Pediatric Psychology, highlighting papers that illustrate how sleep problems are not only commonly comorbid with childhood medical and developmental conditions; they are also likely caused by and contribute to these conditions. In doing so, these coordinated special issues guide clinical care and reveal opportunities for future research. PMID- 27189694 TI - Measuring Medication Adherence in Pediatric Cancer: An Approach to Validation. AB - Objective: This study described the prospective relationship between pharmacological and behavioral measures of 6-mercaptopurine (6MP) medication adherence in a multisite cohort of pediatric patients diagnosed with cancer ( N = 139). Methods: Pharmacological measures (i.e., metabolite concentrations) assessed 6MP intake. Behavioral measures (e.g., electronic monitoring) described adherence patterns over time. Results: Three metabolite profiles were identified across 15 months: one group demonstrated low levels of both metabolites (40.8%) consistent with nonadherence and/or suboptimal therapy; two other groups demonstrated metabolite clusters indicative of adequate adherence (59.2%). Those patients whose metabolite profile demonstrated low levels of both metabolites had consistently lower behavioral adherence rates. Conclusions: To our knowledge, this was the first study to prospectively validate a pharmacological measure of medication adherence with a behavioral adherence measure in a relatively large sample of pediatric patients with cancer. Using multiple methods of adherence measurement could inform clinical care and target patients in need of intervention. PMID- 27189695 TI - Protecting bone in long-term HIV positive patients receiving antiretrovirals. AB - INTRODUCTION: As the population of people living with HIV ages, the increase in non-AIDs morbidities is expected to increase in parallel. Maintaining bone health in those with HIV will be an important area of focus for the HIV clinician to prevent the morbidity and mortality associated with fragility fractures, the principal clinical sequela of low bone mineral density (BMD). Rates of fractures and prevalence of low bone mineral density, a risk factor for future fragility fractures, are already increased in the HIV positive population. AREAS COVERED: This review examines the strategies to maintain bone health in those living with HIV from screening through to managing those with established low BMD or fracture, including the role for choice of or modification of antiretroviral therapy to maintain bone health. Expert commentary: The increasing complexity of managing bone health in the age of succesful antiretroviral therapy and an aging patient population as well as future perspectives which may help achieve the long term aim of minimising the impact of low BMD in those with HIV are discussed and explored. PMID- 27189696 TI - A comparison of age-related changes in axial prestretch in human carotid arteries and in human abdominal aorta. AB - It is known that large arteries in situ are subjected to significant axial prestretch. This prestretch plays an important physiological role in optimizing the biomechanical response of an artery. It is also known that the prestretch declines with age. However, a detailed description of age-related changes in prestretch is available only for the abdominal aorta and for the femoropliteal artery. Our study presents results of measurements of axial prestretch in 229 left common carotid arteries excised in autopsies. It was found that the prestretch of the carotid artery correlates significantly with age ([Formula: see text], p value < 0.001). A linear regression model was used to fit the observations. Simultaneously with the measurement of the prestretch in the carotid artery, the axial prestretch was also measured in abdominal aorta. By comparing data obtained from these locations, it was concluded that the axial prestretch in the carotid artery is greater than in the abdominal aorta, and that atherosclerosis develops more rapidly in the abdominal aorta than in the carotid artery. Histological sections obtained from 8 carotid arteries and aortas suggest that the medial layer of the left common carotid artery is significantly thinner than aortic media (median/IQR: 0.343/0.086 vs. 0.482/0.172 mm, [Formula: see text] in Wilcoxon signed-rank test) and simultaneously that carotid media contains a lower number of elastic membranes (median/IQR: 26.5/11.8 vs. 31.5/11.8, [Formula: see text] in the Wilcoxon signed-rank test). This could be a reason for the different extent of the prestretch observed in aorta and in carotid artery. Our data sample also contains 5 measurements of the axial prestretch in abdominal aortas suffering from an aneurysm. It was found that aneurysmatic aortas also exhibit axial retraction when excised from in situ position. To the best of our knowledge, this is the first time that detailed data characterizing axial prestretch of the human left common carotid artery have been presented. PMID- 27189697 TI - Community Health Workers: a Resource to Support Antipsychotic Medication Adherence. AB - Community health workers (CHWs) are frontline public health workers who are becoming increasingly integrated into medical settings for the prevention, treatment, and control of chronic disease. In particular, they have demonstrated the ability to improve medication adherence in underserved populations. One overlooked population that could benefit from CHW intervention is individuals with severe mental illnesses such as schizophrenia and bipolar disorder. These conditions are disproportionally weighted to economically disadvantaged communities and people of color, and are typically treated using antipsychotic medications. A number of factors, including social disadvantage, contribute to antipsychotic non-adherence, which is highly prevalent and drastically increases the burden of illness and economic impact of these conditions. This commentary examines the ways in which CHWs may be able to best serve individuals with severe mental illness, and proposes methods for facilitating this expanded scope of work. PMID- 27189698 TI - Collaborative Care: a Pilot Study of a Child Psychiatry Outpatient Consultation Model for Primary Care Providers. AB - A Child Psychiatry Consultation Model (CPCM) offering primary care providers (PCPs) expedited access to outpatient child psychiatric consultation regarding management in primary care would allow more children to access mental health services. Yet, little is known about outpatient CPCMs. This pilot study describes an outpatient CPCM for 22 PCPs in a large Northeast Florida county. PCPs referred 81 patients, of which 60 were appropriate for collaborative management and 49 were subsequently seen for outpatient psychiatric consultation. The most common psychiatric diagnoses following consultation were anxiety (57%), ADHD (53%), and depression (39%). Over half (57%) of the patients seen for consultation were discharged to their PCP with appropriate treatment recommendations, and only a small minority (10%) of patients required long-term care by a psychiatrist. This CPCM helped child psychiatrists collaborate with PCPs to deliver mental health services for youth. The CPCM should be considered for adaptation and dissemination. PMID- 27189699 TI - Clinic Outcome Assessment of a Brief Course Neurofeedback for Childhood ADHD Symptoms. PMID- 27189700 TI - Anti-inflammatory activity of polysaccharide from Schizophyllum commune as affected by ultrasonication. AB - Ultrasound treatment was applied to modify the physicochemical properties of an exopolysaccharide from mycelial culture of Schizophyllum commune. Molecular weight (MW) degradation, viscosity and anti-inflammatory property of ultrasonic treated polysaccharide were optimized with response surface methodology. The best ultrasonic parameters were obtained with a three-variable-three-level Box-Behnken design. The optimized conditions for efficient anti-inflammatory activity are initial concentration at 0.4%, ultrasonic power at 600W, and duration of ultrasonic irradiation for 9min. Under these conditions, the nitric oxide inhibition rate was 95+/-0.03% which agreed closely with the predicted value (96%). Average MW of polysaccharide decreased after ultrasonic treatments. The viscosity of degraded polysaccharide dropped compared with native polysaccharide. The anti-inflammatory activity was improved by ultrasound treatment. The results suggested that ultrasound treatment is an effective approach to decrease the MW of polysaccharide with high anti-inflammatory activity. Ultrasonic treatment is a viable modification technology for high MW polymer materials. PMID- 27189701 TI - RBQ3 participates in multiple myeloma cell proliferation, adhesion and chemoresistance. AB - Cell adhesion mediated drug resistance (CAM-DR) is a major factor that impedes the effect of chemotherapy in multiple myeloma (MM). RBQ3, which is a RB-binding protein, played a crucial role in cell cycle process. Here, we reported that RBQ3 expression was increased gradually during the proliferation process of myeloma cells. Knocking down of RBQ3 resulted in cell cycle arrest in G1 phase and increased myeloma cells adherent to fibronectin or bone marrow stromal cells (BMSCs). Furthermore, silencing of RBQ3 reduced sensitivity to chemotherapeutic drugs in myeloma cell lines adherent to BMSCs and reduced two apoptotic marker proteins cleaved caspase-3 and cleaved PARP expression. Besides, we also found that RBQ3 participated in MAPK/ERK signal transduction pathway. In summary, these results may shed new insights into the role of RBQ3 in the development of multiple myeloma. PMID- 27189702 TI - Synthesis, characterization and bioactivities of N,O-carbonylated chitosan. AB - N,O-Carbonylated chitosan derivative (NTCS) was synthesized via oxidation and substitution reaction, respectively. The carboxyethylation of the polysaccharide was identified by Fourier transform infrared (FTIR), (1)H nuclear magnetic resonance (NMR), X-ray diffraction analysis (XRD), Zeta potential measurement and Thermogravimetric analysis (TGA). It is revealed that compared with chitosan (CS), NTCS exhibited an excellent solubility in distilled water, high in vitro bile acid binding capacity, as well as a low viscosity. The in vitro bile acid binding capacity reached 17.21mg/g, which was 4.5-fold higher than that of CS. The results suggest that NTCS may be useful as a potential functional food supplement in food industry or a key ingredient in the pharmaceutical industry. These findings provide important supports for developing new food additive, and expand the scope of application of CS in the food industry. PMID- 27189703 TI - Next-generation sequencing identifies a novel ELAVL1-TYK2 fusion gene in MOLM-16, an AML cell line highly sensitive to the PIM kinase inhibitor AZD1208. PMID- 27189705 TI - A simple screen performed at school entry can predict academic under-achievement at age seven in children born very preterm. AB - AIM: We aimed to compare the academic outcomes of a cohort of children born very preterm (VPT, <32 weeks of gestation) and children born at term at age 7 years and assess the ability of a pre-academic skill screen at age five to predict later academic impairment in children born VPT at age seven. METHODS: One hundred ninety-four children born VPT (born with either gestational age <30 weeks or birthweight <1250 g) and 70 controls born at term from a prospective birth cohort were compared on academic outcomes (Wide Range Achievement Test, WRAT4) at age seven using regression analyses. Receiver-operating characteristic curves were used to determine whether pre-academic skills (Kaufman Survey of Early Academic and Language Skills, K-SEALS) at age five predicted academic impairment at age seven in 174 of the VPT cohort. RESULTS: At the age of 7 years, children born VPT had lower mean word reading (-9.7, 95% CI: -14.7 to -4.6), spelling (-8.3, 95% CI: -13.3 to -3.3) and math computation (-10.9, 95% CI: -15.3 to -6.5) scores (all P-values <=0.001) compared with controls born at term, even after adjusting for social risk and time since school commencement. In terms of pre-academic screening, the Numbers, Letters and Words subtest of the K-SEALS had adequate sensitivity and specificity (70-80%) for predicting children with academic impairment at age seven. CONCLUSIONS: Children born VPT underperformed in academic outcomes at age seven compared with controls born at term. A pre academic screening tool used at school entry can predict children born VPT at risk of academic impairment at age seven who could benefit from targeted early intervention. PMID- 27189706 TI - Nivolumab: A Review in Advanced Nonsquamous Non-Small Cell Lung Cancer. AB - The programmed death (PD)-1 immune checkpoint inhibitor nivolumab (Opdivo((r))) is approved in the USA for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) who have progression on or after platinum-based chemotherapy and in the EU for the treatment of adults with locally advanced or metastatic NSCLC after prior chemotherapy. In previously-treated patients with advanced nonsquamous NSCLC, overall survival was significantly prolonged and the overall response rate was significantly higher in patients who received intravenous nivolumab 3 mg/kg every 2 weeks versus intravenous docetaxel in the pivotal CheckMate 057 trial. Progression-free survival did not significantly differ between patients receiving nivolumab and those receiving docetaxel. Intravenous nivolumab had a manageable adverse event profile (including immune mediated adverse events) and was better tolerated than docetaxel in the CheckMate 057 trial. Thus, nivolumab is an important new option for use in previously treated patients with advanced nonsquamous NSCLC. PMID- 27189707 TI - Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide: A Review in HIV-1 Infection. AB - Tenofovir alafenamide (tenofovir AF) is a novel oral prodrug of the nucleos(t)ide reverse transcriptase inhibitor (NRTI) tenofovir that has several pharmacological advantages over tenofovir disoproxil fumarate (tenofovir DF), including increased plasma stability and reduced tenofovir systemic exposure. Tenofovir AF has been coformulated with elvitegravir, cobicistat and emtricitabine as a once-daily, single-tablet regimen (elvitegravir/cobicistat/emtricitabine/tenofovir AF; Genvoya((r))) for the treatment of adults and adolescents with HIV-1 infection. With regard to establishing and/or maintaining virological suppression over 48 weeks in randomized, phase III trials, elvitegravir/cobicistat/emtricitabine/tenofovir AF was noninferior to elvitegravir/cobicistat/emtricitabine/tenofovir DF in antiretroviral therapy (ART)-naive adults, and statistically superior (subsequent to established noninferiority) to ongoing treatment with tenofovir DF-containing regimens in ART experienced adults with virological suppression. In single-arm, phase III trials, elvitegravir/cobicistat/emtricitabine/tenofovir AF also provided high rates of virological suppression among ART-naive adolescents and ART-experienced adults with stable renal impairment. In general, elvitegravir/cobicistat/emtricitabine/tenofovir AF was well tolerated and associated with more favourable renal and bone parameters, but a less favourable lipid profile, than tenofovir DF-containing regimens. Thus, elvitegravir/cobicistat/emtricitabine/tenofovir AF is an alternative single tablet regimen for adults and adolescents with HIV-1 infection, particularly those with an estimated creatinine clearance of >=30 to <50 mL/min or an increased risk of tenofovir DF-related bone toxicity. PMID- 27189708 TI - Are trees able to grow in periods of stem shrinkage? AB - Separating continuously measured stem radius (SR) fluctuations into growth induced irreversible stem expansion (GRO) and tree water deficit-induced reversible stem shrinkage (TWD) requires a conceptualization of potential growth processes that may occur during periods of shrinking and expanding SR below a precedent maximum. Here, we investigated two physiological concepts: the linear growth (LG) concept, assuming linear growth, versus the zero growth (ZG) concept, assuming no growth during periods of stem shrinkage. We evaluated the physiological mechanisms underlying these two concepts and assessed their respective plausibilities using SR data obtained from 15 deciduous and evergreen trees. The application of the LG concept produced steady growth rates, whereas growth rates varied strongly under the ZG concept, more in accordance with mechanistic expectations. Further, growth increased for a maximum of 120 min after periods of stem shrinkage, indicating limited growth activity during those periods. However, this extra growth was found to be a small fraction of total growth only. Furthermore, TWD under the ZG concept was better explained by a hydraulic plant model than TWD under the LG concept. We conclude that periods of stem shrinkage allow for very little growth in the four tree species investigated. However, further studies should focus on obtaining independent growth data to ultimately validate these findings. PMID- 27189709 TI - Access to Rehabilitation at Six Months Post Stroke: A Profile from the Action on Secondary Prevention Interventions and Rehabilitation in Stroke (ASPIRE-S) Study. AB - BACKGROUND AND PURPOSE: Stroke is the third leading cause of death and disability. Few studies have assessed the profile and adequacy of access to rehabilitation services after ischaemic stroke both in the inpatient and community setting. The objectives of the Action on Secondary Prevention Interventions and Rehabilitation in Stroke (ASPIRE-S) study were to assess the disability and rehabilitation profile, adherence with rehabilitation recommendations and needs of patients 6 months following hospital admission for stroke. METHODS: A rehabilitation prescription was completed before hospital discharge for each participant, and adherence to this prescription was assessed at 6 months to determine whether patients received their recommended rehabilitation needs. RESULTS: Two hundred and fifty six patients were recruited to ASPIRE-S. The average age was 69 (SD 12.8). A majority (n = 221, 86%) were referred to the hospital multidisciplinary team, 59% (n = 132) were referred to all services (physiotherapy (PT), occupational therapy (OT), speech and language therapy (SLT)). Fifty-four percent (n = 119) of patients (seen by the multidisciplinary team) were referred for further rehabilitation in the community on discharge. Of these 119 patients, 112 (95%) recalled receiving community rehabilitation services. However, while most (68%) patients were referred for several disciplines (PT, OT, SLT), the most commonly recalled therapy (55%) was from a single discipline. The most commonly recommended frequency of therapy required was on a weekly basis. Sixty-one patients (51%) reported a delay in services, with some still awaiting services at 6 months. CONCLUSION: Results from this prospective study revealed that a significant number of patients (57%) did not receive the therapy recommended on discharge. Future initiatives should include the development of policies, which support more effective, equitable multidisciplinary rehabilitation for stroke patients in the community. PMID- 27189710 TI - Interactions between KSHV ORF57 and the novel human TREX proteins, CHTOP and CIP29. AB - The coupling of mRNA processing steps is essential for precise and efficient gene expression. The human transcription/export (hTREX) complex is a highly conserved multi-protein complex responsible for eukaryotic mRNA stability and nuclear export. We have previously shown that the Kaposi's sarcoma-associated open reading frame 57 (ORF57) protein orchestrates the recruitment of the hTREX complex onto viral intronless mRNA, forming a stable and export-competent viral ribonucleoprotein particle (vRNP). Recently, additional cellular proteins, namely CHTOP, CIP29 and POLDIP3 have been proposed as novel hTREX components. Herein, we extend our previous research and provide evidence that ORF57 interacts with CHTOP and CIP29, in contrast to POLDIP3. Moreover, depletion studies show both CHTOP and CIP29 effect ORF57-mediated viral mRNA processing. As such, these results suggest both CHTOP and CIP29 are hTREX components and are recruited to an ORF57 mediated vRNP. PMID- 27189711 TI - "Suicide shall cease to be a crime": suicide and undetermined death trends 1970 2000 before and after the decriminalization of suicide in Ireland 1993. AB - INTRODUCTION: Suicide is criminalized in more than 100 countries around the world. A dearth of research exists into the effect of suicide legislation on suicide rates and available statistics are mixed. MATERIALS AND METHODS: This study investigates 10,353 suicide deaths in Ireland that took place between 1970 and 2000. Irish 1970-2000 annual suicide data were obtained from the Central Statistics Office and modelled via a negative binomial regression approach. We examined the effect of suicide legislation on different age groups and on both sexes. We used Bonferroni correction for multiple modelling. Statistical analysis was performed using the R statistical package version 3.1.2. The coefficient for the effect of suicide act on overall suicide deaths was -9.094 (95 % confidence interval (CI) -34.086 to 15.899), statistically non-significant (p = 0.476). The coefficient for the effect suicide act on undetermined deaths was statistically significant (p < 0.001) and was estimated to be -644.4 (95 % CI -818.6 to 469.9). CONCLUSION: The results of our study indicate that legalization of suicide is not associated with a significant increase in subsequent suicide deaths. However, undetermined death verdict rates have significantly dropped following legalization of suicide. PMID- 27189713 TI - Identifying content-based and relational techniques to change behaviour in motivational interviewing. AB - Motivational interviewing (MI) is a complex intervention comprising multiple techniques aimed at changing health-related motivation and behaviour. However, MI techniques have not been systematically isolated and classified. This study aimed to identify the techniques unique to MI, classify them as content-related or relational, and evaluate the extent to which they overlap with techniques from the behaviour change technique taxonomy version 1 [BCTTv1; Michie, S., Richardson, M., Johnston, M., Abraham, C., Francis, J., Hardeman, W., ... Wood, C. E. (2013). The behavior change technique taxonomy (v1) of 93 hierarchically clustered techniques: Building an international consensus for the reporting of behavior change interventions. Annals of Behavioral Medicine, 46, 81-95]. Behaviour change experts (n = 3) content-analysed MI techniques based on Miller and Rollnick's [(2013). Motivational interviewing: Preparing people for change (3rd ed.). New York: Guildford Press] conceptualisation. Each technique was then coded for independence and uniqueness by independent experts (n = 10). The experts also compared each MI technique to those from the BCTTv1. Experts identified 38 distinct MI techniques with high agreement on clarity, uniqueness, preciseness, and distinctiveness ratings. Of the identified techniques, 16 were classified as relational techniques. The remaining 22 techniques were classified as content based. Sixteen of the MI techniques were identified as having substantial overlap with techniques from the BCTTv1. The isolation and classification of MI techniques will provide researchers with the necessary tools to clearly specify MI interventions and test the main and interactive effects of the techniques on health behaviour. The distinction between relational and content-based techniques within MI is also an important advance, recognising that changes in motivation and behaviour in MI is a function of both intervention content and the interpersonal style in which the content is delivered. PMID- 27189714 TI - Editorial: Telocytes in Regeneration and Repair. PMID- 27189712 TI - Identification and Characterization of Epstein-Barr Virus Genomes in Lung Carcinoma Biopsy Samples by Next-Generation Sequencing Technology. AB - Epstein-Barr virus (EBV) has been detected in the tumor cells of several cancers, including some cases of lung carcinoma (LC). However, the genomic characteristics and diversity of EBV strains associated with LC are poorly understood. In this study, we sequenced the EBV genomes isolated from four primary LC tumor biopsy samples, designated LC1 to LC4. Comparative analysis demonstrated that LC strains were more closely related to GD1 strain. Compared to GD1 reference genome, a total of 520 variations in all, including 498 substitutions, 12 insertions, and 10 deletions were found. Latent genes were found to harbor the most numbers of nonsynonymous mutations. Phylogenetic analysis showed that all LC strains were closely related to Asian EBV strains, whereas different from African/American strains. LC2 genome was distinct from the other three LC genomes, suggesting at least two parental lineages of EBV among the LC genomes may exist. All LC strains could be classified as China 1 and V-val subtype according to the amino acid sequence of LMP1 and EBNA1, respectively. In conclusion, our results showed the genomic diversity among EBV genomes isolated from LC, which might facilitate to uncover the previously unknown variations of pathogenic significance. PMID- 27189715 TI - Telocytes in Cardiac Protection. AB - Telocytes (TCs) are a distinct type of stromal cells with extremely thin and long prolongations called telopodes (Tps). TCs have been ubiquitously reported in almost all tissues and organs across species including heart. TCs are distinct from fibroblasts as evidenced by ultrastructural characteristics, immunohistochemistry features, gene profiles, proteome features, and miRNA signatures. By means of heterocellular junctions and extracellular vesicles, TCs may be able to regulate cardiac stem cells, angiogenesis, and anti-fibrosis. Therapeutic effects of cardiac TCs in myocardium infarction have been demonstrated. Cardiac TCs could be a source of cardiac repair and protection. PMID- 27189716 TI - Editorial: Role of Cancer Stem Cells in Common Gastrointestinal Cancers: From Pathogenesis to Therapeutic Targets. PMID- 27189718 TI - Prostate cancer glands with cribriform architecture and with glomeruloid features should be considered as Gleason pattern 4 and not pattern 3. PMID- 27189717 TI - Differential effects of inhibitors of the PI3K/mTOR pathway on the expansion and functionality of regulatory T cells. AB - The PI3K/mTOR pathway is commonly deregulated in cancer. mTOR inhibitors are registered for the treatment of several solid tumors and novel inhibitors are explored clinically. Notably, this pathway also plays an important role in immunoregulation. While mTOR inhibitors block cell cycle progression of conventional T cells (Tconv), they also result in the expansion of CD4(+)CD25(hi)FOXP3(+) regulatory T cells (Tregs), and this likely limits their clinical antitumor efficacy. Here, we compared the effects of dual mTOR/PI3K inhibition (using BEZ235) to single PI3K (using BKM120) or mTOR inhibition (using rapamycin and everolimus) on Treg expansion and functionality. Whereas rapamycin, everolimus and BEZ235 effected a relative expansion benefit for Tregs and increased their overall suppressive activity, BKM120 allowed for similar expansion rates of Tregs and Tconv without altering their overall suppressive activity. Therefore, PI3K inhibition alone might offer antitumor efficacy without the detrimental selective expansion of Tregs associated with mTOR inhibition. PMID- 27189719 TI - Fractal analysis reveals subclasses of neurons and suggests an explanation of their spontaneous activity. AB - The present work used fractal time series analysis (detrended fluctuation analysis; DFA) to examine the spontaneous activity of single neurons in an anesthetized animal model, specifically, the mitral cells in the rat main olfactory bulb. DFA bolstered previous research in suggesting two subclasses of mitral cells. Although there was no difference in the fractal scaling of the interspike interval series at the shorter timescales, there was a significant difference at longer timescales. Neurons in Group B exhibited fractal, power-law scaled interspike intervals, whereas neurons in Group A exhibited random variation. These results raise questions about the role of these different cells within the olfactory bulb and potential explanations of their dynamics. Specifically, self-organized criticality has been proposed as an explanation of fractal scaling in many natural systems, including neural systems. However, this theory is based on certain assumptions that do not clearly hold in the case of spontaneous neural activity, which likely reflects intrinsic cell dynamics rather than activity driven by external stimulation. Moreover, it is unclear how self organized criticality might account for the random dynamics observed in Group A, and how these random dynamics might serve some functional role when embedded in the typical activity of the olfactory bulb. These theoretical considerations provide direction for additional experimental work. PMID- 27189722 TI - Recurrent Hypertensive Crises in an Endoscopist: A Possible Occupational Link. PMID- 27189720 TI - Anatomical and molecular consequences of Unilateral Naris Closure on two populations of olfactory sensory neurons expressing defined odorant receptors. AB - Mammalian olfactory sensory neurons (OSNs), the primary elements of the olfactory system, are located in the olfactory epithelium lining the nasal cavity. Exposed to the environment, their lifespan is short. Consequently, OSNs are regularly regenerated and several reports show that activity strongly modulates their development and regeneration: the peripheral olfactory system can adjust to the amount of stimulus through compensatory mechanisms. Unilateral naris occlusion (UNO) was frequently used to investigate this mechanism at the entire epithelium level. However, there is little data regarding the effects of UNO at the cellular level, especially on individual neuronal populations expressing a defined odorant receptor. Here, using UNO during the first three postnatal weeks, we analyzed the anatomical and molecular consequences of sensory deprivation in OSNs populations expressing the MOR23 and M71 receptors. The density of MOR23-expressing neurons is decreased in the closed side while UNO does not affect the density of M71 expressing neurons. Using Real Time qPCR on isolated neurons, we observed that UNO modulates the transcript levels for transduction pathway proteins (odorant receptors, CNGA2, PDE1c). The transcripts modulated by UNO will differ between populations depending on the receptor expressed. These results suggest that sensory deprivation will have different effects on different OSNs' populations. As a consequence, early experience will shape the functional properties of OSNs differently depending on the type of odorant receptor they express. PMID- 27189723 TI - Medical Rescue of China International Search & Rescue Team (CISAR) in Nepal Earthquake. AB - On April 25, 2015, a massive 8.1-magnitude earthquake struck Nepal at 2:11 pm (Beijing time). The 68-member-strong China International Search & Rescue Team (CISAR) left for Nepal at 6 am, April 26, to help with relief work. The CISAR was the first foreign team to rescue a survivor who was trapped beneath the rubble in the Gongabu area after the earthquake. On May 8, the team fulfilled the search and-rescue mission and returned to Beijing. During the 2 weeks of rescue work, the team treated more than 3700 victims and cleared approximately 430 buildings. In this rescue mission, 10 experienced medical officers (including nine doctors and a nurse) from the General Hospital of Chinese People's Armed Police Force (PAP) comprised the medical team of CISAR. In this report, we focus on the medical rescues by CISAR and discuss the characteristics of the medical rescue in Nepal. (Disaster Med Public Health Preparedness. 2018;12:536-538). PMID- 27189721 TI - The Impact of African American Parents' Racial Discrimination Experiences and Perceived Neighborhood Cohesion on their Racial Socialization Practices. AB - Parental racial socialization is a parenting tool used to prepare African American adolescents for managing racial stressors. While it is known that parents' racial discrimination experiences affect the racial socialization messages they provide, little is known about the influence of factors that promote supportive and communal parenting, such as perceived neighborhood cohesion. In cohesive neighborhoods, neighbors may help parents address racial discrimination by monitoring youth and conveying racial socialization messages; additionally, the effect of neighborhood cohesion on parents' racial socialization may differ for boys and girls because parents socialize adolescents about race differently based on expected encounters with racial discrimination. Therefore, the current study examines how parents' perception of neighborhood cohesion and adolescents' gender moderate associations between parents' racial discrimination experiences and the racial socialization messages they deliver to their adolescents. Participants were a community sample of 608 African American adolescents (54 % girls; mean age = 15.5) and their primary caregivers (86 % biological mothers; mean age = 42.0). Structural equation modeling indicated that parental racial discrimination was associated with more promotion of mistrust messages for boys and girls in communities with low neighborhood cohesion. In addition, parental racial discrimination was associated with more cultural socialization messages about racial pride and history for boys in neighborhoods with low neighborhood cohesion. The findings suggest that parents' racial socialization messages are influenced by their own racial discrimination experiences and the cohesiveness of the neighborhood; furthermore, the content of parental messages delivered varies based on adolescents' gender. PMID- 27189724 TI - Power Calculation of Multi-step Combined Principal Components with Applications to Genetic Association Studies. AB - Principal component analysis (PCA) is a useful tool to identify important linear combination of correlated variables in multivariate analysis and has been applied to detect association between genetic variants and human complex diseases of interest. How to choose adequate number of principal components (PCs) to represent the original system in an optimal way is a key issue for PCA. Note that the traditional PCA, only using a few top PCs while discarding the other PCs, might significantly lose power in genetic association studies if all the PCs contain non-ignorable signals. In order to make full use of information from all PCs, Aschard and his colleagues have proposed a multi-step combined PCs method (named mCPC) recently, which performs well especially when several traits are highly correlated. However, the power superiority of mCPC has just been illustrated by simulation, while the theoretical power performance of mCPC has not been studied yet. In this work, we attempt to investigate theoretical properties of mCPC and further propose a novel and efficient strategy to combine PCs. Extensive simulation results confirm that the proposed method is more robust than existing procedures. A real data application to detect the association between gene TRAF1-C5 and rheumatoid arthritis further shows good performance of the proposed procedure. PMID- 27189725 TI - Predicting delirium after hip fracture with a 2-min cognitive screen: prospective cohort study. AB - BACKGROUND: although the importance of identifying hip fracture patients with high risk for delirium has been well established, considerable controversy exists over the choice of the screening tool. The most commonly used cognitive screeners take an excessive amount of time and include drawing tasks that can be troublesome for individuals with hip fracture who are invariably lying in bed. OBJECTIVE: to evaluate the properties of the 10-point Cognitive Screener (10-CS), a 2-min bedside tool, for predicting delirium in older adults with hip fracture. DESIGN: prospective cohort study. SETTING: a tertiary referral hospital in Sao Paulo, Brazil. SUBJECTS: non-delirious older adults with hip fracture (n = 147). METHODS: the 10-CS was administered as a baseline predictor. The test is composed of three-item temporal orientation (date, month, year), category fluency (animals in 1 min) and three-word recall. Incident delirium has been diagnosed according to the Confusion Assessment Method (CAM) that was administered daily from admission to discharge. RESULTS: during hospitalisation, 61 (41.5%) patients developed delirium. The 10-CS presented excellent accuracy for predicting delirium, with an area under ROC curve of 0.83 (95% CI 0.76-0.89). After adjusting for demographic and clinical variables, participants with probable cognitive impairment (score <= 5) were more likely to develop delirium (HR = 7.48; 95% CI 2.2-25.4) compared with participants with a normal score. Lower scores on the 10-CS were also independently associated with a longer length of stay. CONCLUSIONS: the 10-CS is an easy-to-use bedside tool with adequate properties to stratify the risk of delirium in older adults with hip fracture. PMID- 27189727 TI - The development of a geriatric postgraduate education assessment instrument using a modified Delphi procedure. AB - There is currently wide variation in the structure and content of higher medical training in geriatric medicine across Europe and no common framework within which existing efforts can be compared. We set out to develop an audit tool to compare training between countries. An initial review of indexed and grey literature was used to develop an audit tool which was used as the basis of an Internet-based modified Delphi process incorporating the views of 14 expert geriatricians from across Europe. Items in the audit tool were included or excluded when supported by >=75% or <50% of respondents, respectively. Items supported by 50-74% of respondents were carried forward with additional suggestions and modifications included following Round 1. Thirteen experts representing 12 countries responded to both rounds. 40/45 items were supported at Round 1. Five items were carried forward. A further 13 elements were introduced for consideration at Round 2. Consensus was gained after the second round. The final tool describes 52 items across four domains: general considerations, topics referring to knowledge in patient care, different roles that should be considered in medical training and topics regarding assessment. The resulting tool can be used as a basis for comparing higher medical training programmes in geriatric medicine between countries. Individual countries can use this to audit current practice. At an European Union level, the insights gained through such audit will form the basis of future work to develop an agreed postgraduate curriculum in the specialty. PMID- 27189726 TI - Intellectual ability in young adulthood as an antecedent of physical functioning in older age. AB - OBJECTIVES: low cognitive ability is associated with subsequent functional disability. Whether this association extends across adult life has been little studied. The aim of this study was to examine the association between intellectual ability in young adulthood and physical functioning during a 10-year follow-up in older age. METHODS: three hundred and sixty persons of the Helsinki Birth Cohort Study (HBCS) male members, born between 1934 and 1944 and residing in Finland in 1971, took part in The Finnish Defence Forces Basic Intellectual Ability Test during the first 2 weeks of their military service training between 1952 and 1972. Their physical functioning was assessed twice using the Short Form 36 (SF-36) questionnaire at average ages of 61 and 71 years. A longitudinal path model linking Intellectual Ability Test score to the physical functioning assessments was used to explore the effect of intellectual ability in young adulthood on physical functioning in older age. RESULTS: after adjustments for age at measurement, childhood socioeconomic status and adult BMI (kg/m(2)), better intellectual ability total and arithmetic and verbal reasoning subtest scores in young adulthood predicted better physical functioning at age 61 years (P values <0.021). Intellectual ability total and arithmetic and verbal reasoning subtest scores in young adulthood had indirect effects on physical functioning at age 71 years (P values <0.022) through better physical functioning at age 61 years. Adjustment for main chronic diseases did not change the results materially. CONCLUSION: better early-life intellectual ability helps in maintaining better physical functioning in older age. PMID- 27189728 TI - Neuropathic orofacial pain in the older person: the role of advanced imaging. PMID- 27189730 TI - 'Exposing' the source of sepsis in the older patient: have you checked the catheter? PMID- 27189731 TI - First-principles calculated decomposition pathways for LiBH4 nanoclusters. AB - We analyze thermodynamic stability and decomposition pathways of LiBH4 nanoclusters using grand-canonical free-energy minimization based on total energies and vibrational frequencies obtained from density-functional theory (DFT) calculations. We consider (LiBH4)n nanoclusters with n = 2 to 12 as reactants, while the possible products include (Li)n, (B)n, (LiB)n, (LiH)n, and Li2BnHn; off-stoichiometric LinBnHm (m <= 4n) clusters were considered for n = 2, 3, and 6. Cluster ground-state configurations have been predicted using prototype electrostatic ground-state (PEGS) and genetic algorithm (GA) based structural optimizations. Free-energy calculations show hydrogen release pathways markedly differ from those in bulk LiBH4. While experiments have found that the bulk material decomposes into LiH and B, with Li2B12H12 as a kinetically inhibited intermediate phase, (LiBH4)n nanoclusters with n <= 12 are predicted to decompose into mixed LinBn clusters via a series of intermediate clusters of LinBnHm (m <= 4n). The calculated pressure-composition isotherms and temperature-pressure isobars exhibit sloping plateaus due to finite size effects on reaction thermodynamics. Generally, decomposition temperatures of free-standing clusters are found to increase with decreasing cluster size due to thermodynamic destabilization of reaction products. PMID- 27189729 TI - Physical activity and incidence of sarcopenia: the population-based AGES Reykjavik Study. AB - BACKGROUND: the prevalence of sarcopenia increases with age. Physical activity might slow the rate of muscle loss and therewith the incidence of sarcopenia. OBJECTIVE: to examine the association of physical activity with incident sarcopenia over a 5-year period. DESIGN: data from the population-based Age, Gene/Environment, Susceptibility-Reykjavik Study were used. SETTING: people residing in the Reykjavik area at the start of the study. SUBJECTS: the study included people aged 66-93 years (n = 2309). METHODS: the amount of moderate vigorous physical activity (MVPA) was assessed by a self-reported questionnaire. Sarcopenia was identified using the European Working Group on Sarcopenia in Older People algorithm, including muscle mass (computed tomography imaging), grip strength (computerised dynamometer) and gait speed (6 m). RESULTS: mean age of the participants was 74.9 +/- 4.7 years. The prevalence of sarcopenia was 7.3% at baseline and 16.8% at follow-up. The incidence proportion of sarcopenia over 5 years was 14.8% in the least-active individuals and 9.0% in the most-active individuals. Compared with the least-active participants, those reporting a moderate-high amount of MVPA had a significantly lower likelihood of incident sarcopenia (OR = 0.64, 95% CI 0.45-0.91). Participants with a high amount of MVPA had higher baseline levels of muscle mass, strength and walking speed, but baseline MVPA was not associated with the rate of muscle loss. CONCLUSION: a higher amount of MVPA seems to contribute to counteracting the development of sarcopenia. To delay the onset of sarcopenia and its potential adverse outcomes, attention should be paid to increasing physical activity levels in older adults. PMID- 27189733 TI - Trafficking and Health: A Systematic Review of Research Methods. AB - Trafficking in persons (TIP) is a human rights violation with serious public health consequences. Unfortunately, assessing TIP and its health sequelae rigorously and reliably is challenging due to TIP's clandestine nature, variation in definitions of TIP, and the need to use research methods that ensure studies are ethical and feasible. To help guide practice, policy, and research to assess TIP and health, we undertook a systematic literature review of 70 peer-reviewed, published articles to (a) identify TIP and health research methods being used, (b) determine what we can learn about TIP and health from these varied methodologies, and (c) determine the gaps that exist in health-focused TIP research. Results revealed that there are various quantitative and qualitative data collection and analysis methods being used to investigate TIP and health. Furthermore, findings show that the limitations of current methodologies affect what is known about TIP and health. In particular, varying definitions, participant recruitment strategies, ethical standards, and outcome measures all affect what is known about TIP and health. Moreover, findings demonstrate an urgent need for representative and nonpurposive recruitment strategies in future investigations of TIP and health as well as research on risk and protective factors related to TIP and health, intervention effectiveness, long-term health outcomes, and research on trafficked people beyond women trafficked for sex. We offer recommendations for research, policy, and practice based on review results. PMID- 27189735 TI - Surface tension measurement from the indentation of clamped thin films. AB - We developed an indentation technique to measure the surface tension of relatively stiff solids. In the proposed method, a suspended thin solid film is indented by a rigid sphere and its deflection is measured by optical interferometry. The film deflection is jointly resisted by surface tension, elasticity and residual stress. Using a version of nonlinear von Karman plate theory that includes surface tension, we are able to separate the contribution of elasticity to the total tension in the film. Surface tension is determined by extrapolating the sum of surface tension and residual stress to zero film thickness. We measured the surface tension of polydimethylsiloxane (PDMS) using this technique and obtained a value of 19.5 +/- 3.6 mN m(-1), consistent with the surface energy of PDMS reported in the literature. PMID- 27189732 TI - Benign hepatocellular nodules of healthy liver: focal nodular hyperplasia and hepatocellular adenoma. AB - Owing to the progress of imaging techniques, benign hepatocellular nodules are increasingly discovered in the clinical practice. This group of lesions mostly arises in the context of a putatively normal healthy liver and includes either pseudotumoral and tumoral nodules. Focal nodular hyperplasia and hepatocellular adenoma are prototypical examples of these two categories of nodules. In this review we aim to report the main pathological criteria of differential diagnosis between focal nodular hyperplasia and hepatocellular adenoma, which mainly rests upon morphological and phenotypical features. We also emphasize that for a correct diagnosis the clinical context such as sex, age, assumption of oral contraceptives, associated metabolic or vascular disturbances is of paramount importance. While focal nodular hyperplasia is a single entity epidemiologically more frequent than adenoma, the latter is representative of a more heterogeneous group which has been recently and extensively characterized from a clinical, morphological, phenotypical and molecular profile. The use of the liver biopsy in addition to imaging and the clinical context are important diagnostic tools of these lesions. In this review we will survey their systematic pathobiology and propose a diagnostic algorithm helpful to increase the diagnostic accuracy of not dedicated liver pathologists. The differential diagnosis between so-called typical and atypical adenoma and well differentiated hepatocellular carcinoma will also be discussed. PMID- 27189736 TI - IL-17A impairs host tolerance during airway chronic infection by Pseudomonas aeruginosa. AB - Resistance and tolerance mechanisms participate to the interplay between host and pathogens. IL-17-mediated response has been shown to be crucial for host resistance to respiratory infections, whereas its role in host tolerance during chronic airway colonization is still unclear. Here, we investigated whether IL-17 mediated response modulates mechanisms of host tolerance during airways chronic infection by P. aeruginosa. First, we found that IL-17A levels were sustained in mice at both early and advanced stages of P. aeruginosa chronic infection and confirmed these observations in human respiratory samples from cystic fibrosis patients infected by P. aeruginosa. Using IL-17a(-/-) or IL-17ra(-/-) mice, we found that the deficiency of IL-17A/IL-17RA axis was associated with: i) increased incidence of chronic infection and bacterial burden, indicating its role in the host resistance to P. aeruginosa; ii) reduced cytokine levels (KC), tissue innate immune cells and markers of tissue damage (pro-MMP-9, elastin degradation, TGF-beta1), proving alteration of host tolerance. Blockade of IL-17A activity by a monoclonal antibody, started when chronic infection is established, did not alter host resistance but increased tolerance. In conclusion, this study identifies IL-17-mediated response as a negative regulator of host tolerance during P. aeruginosa chronic airway infection. PMID- 27189738 TI - Evolution of Locked Nailing. PMID- 27189739 TI - Sequence-based separation of single-stranded DNA at high salt concentrations in capillary zone electrophoresis. AB - DNA separation by fragment length can be readily achieved using sieving gels in electrophoresis. Separation by sequence has not been as simple, generally requiring adequate differences in native or induced conformation between single or hybridized strands or differences in thermal or chemical stability of hybridized strands. Previously, it was shown that four single-stranded DNA (ssDNA) 76-mers that differ by only a few A-G substitutions could be separated based solely on sequence by adding guanosine-5'-monophosphate to the running buffer in capillary zone electrophoresis (CZE). The separation was attributed to interactions of the ssDNA with self-assembled guanine-tetrad structures; however, subsequent studies of an expanded set of ten 76-mers showed that the separation was a more general phenomenon that occurred at high salt concentrations. With the long-term goal of using experimental and computational methods to provide insight into the basis of the separation, a set of ssDNA 15-mers was designed including a poly(dT) 15-mer and nine variants. Separations were performed using fluorescent labeled ssDNA in CZE with laser-induced fluorescence detection. Results show that separation improves with increasing buffer concentration and decreasing temperature, due at least in part to longer separation times. Migration times increase with increasing purine content, with A having a much larger effect that G. Circular dichroism spectra of the mixtures of the strands suggest that the separation is not due to changes in conformation of the ssDNA at high salt concentrations. PMID- 27189740 TI - Photoinduced charge-transfer dynamics simulations in noncovalently bonded molecular aggregates. AB - The rational design of new materials as prototype systems for organic solar cells remains challenging. Perylene diimide has emerged as a promising material to replace fullerene derivatives because of its synthetic flexibility, leading to the manipulation of their optical properties. As a result of their fused aromatic core that favors pi-pi stacking interactions, the aggregation of these molecules can reach highly ordered nanostructures as one-dimensional nanofibers, with a fast photoinduced charge transfer mechanism. In this article, we present an atomistic description of the photoexcited exciton dynamics in noncovalently bonded perylene diimides by time integration of the electron density in the presence of external time varying electric fields. We show that our approach is able to capture and explain the physics that underlies the charge transport mechanism through perylene diimide aggregates. PMID- 27189737 TI - Neuronal activity mediated regulation of glutamate transporter GLT-1 surface diffusion in rat astrocytes in dissociated and slice cultures. AB - The astrocytic GLT-1 (or EAAT2) is the major glutamate transporter for clearing synaptic glutamate. While the diffusion dynamics of neurotransmitter receptors at the neuronal surface are well understood, far less is known regarding the surface trafficking of transporters in subcellular domains of the astrocyte membrane. Here, we have used live-cell imaging to study the mechanisms regulating GLT-1 surface diffusion in astrocytes in dissociated and brain slice cultures. Using GFP-time lapse imaging, we show that GLT-1 forms stable clusters that are dispersed rapidly and reversibly upon glutamate treatment in a transporter activity-dependent manner. Fluorescence recovery after photobleaching and single particle tracking using quantum dots revealed that clustered GLT-1 is more stable than diffuse GLT-1 and that glutamate increases GLT-1 surface diffusion in the astrocyte membrane. Interestingly, the two main GLT-1 isoforms expressed in the brain, GLT-1a and GLT-1b, are both found to be stabilized opposed to synapses under basal conditions, with GLT-1b more so. GLT-1 surface mobility is increased in proximity to activated synapses and alterations of neuronal activity can bidirectionally modulate the dynamics of both GLT-1 isoforms. Altogether, these data reveal that astrocytic GLT-1 surface mobility, via its transport activity, is modulated during neuronal firing, which may be a key process for shaping glutamate clearance and glutamatergic synaptic transmission. GLIA 2016;64:1252 1264. PMID- 27189742 TI - Impact of students in non-teaching hospitals. AB - BACKGROUND: The placement of medical students in non-teaching hospitals is the norm worldwide. The suggestion that teaching standards are inferior in non teaching hospitals has been studied and refuted. This study explores this from a different perspective: the impact of medical student presence on the teachers, hospital environment and patient care at King Saud Medical City, as assessed by clinical supervisors. METHODS: A questionnaire was distributed to clinical supervisors on the internal medical rotation at King Saud Medical City, College of Medicine, Al Imam Muhammed Ibn Saud Islamic University, Saudi Arabia. The view of supervisors on the impact of medical students on clinical supervisors themselves, the hospital environment and patient care was elicited. This study explores... the impact of student presence on teachers, hospital environment and patient care RESULTS: Between 69 and 84 per cent of respondents believed medical students had a positive effect on their practice, including increased reflective practice, increased enthusiasm and prompts to review basic medical knowledge. Accordingly, 85 per cent of clinical supervisors believed that their continuing medical education had been improved. A majority of respondents reported a positive impact on the hospital environment, with 66 per cent believing patient care to have improved. DISCUSSION: Numerous studies have confirmed the standard of education in non-teaching hospitals to be as good as or better than in the corresponding teaching hospitals. It has also been shown that non-teaching hospitals fulfill the needs of medical students. It is suggested that this study demonstrates a positive impact of medical students on the clinical teachers in a non-teaching hospital in Saudi Arabia, with a significant proportion of teachers believing the hospital environment and quality of care to be improved by their presence. PMID- 27189741 TI - Preventive dental care in older adults with diabetes. AB - BACKGROUND: The association between poor oral health and diabetes is well documented. Preventive oral health care is, therefore, strongly indicated for people with diabetes. The authors conducted a study to determine if there was a difference in preventive dental care use among older adults with diabetes in 2002 and in 2011 and to compare preventive dental care use by older adults with and without diabetes in 2002 and in 2011. METHODS: The authors used a data sample of participants from the Medicare Current Beneficiary Survey that included older (65 years and older) fee-for-service Medicare beneficiaries. The key outcome was self reported preventive dental care. In 2002, there were 8,725 participants; in 2011, there were 7,425 participants. The authors conducted chi(2) and logistic regression analyses. RESULTS: In 2002, 28.8% of participants with diabetes had preventive dental care. In 2011, this percentage increased to 36.0%. Similar results were seen among participants without diabetes (42.9% in 2002 and 45.5% in 2011). The increase in preventive dental care was statistically significant for participants with and without diabetes. The participants with diabetes, as compared with participants without diabetes, remained statistically less likely to have had preventive dental care in adjusted logistic regression analysis with and without considering the interaction between observation year and diabetes (adjusted odds ratios, 0.73 and 0.86, respectively). CONCLUSIONS: Although the percentage increase in participants with diabetes receiving preventive dental care is welcomed, older adults with diabetes continue to have substantial preventive dental care needs. PRACTICAL IMPLICATIONS: Additional efforts are needed to encourage people with diabetes to obtain preventive dental care. PMID- 27189743 TI - Monodisperse light color nanoparticle ink toward chromatic electrophoretic displays. AB - The facile synthesis of nanoparticles for precise image control and fast response of chromatic electrophoretic displays (EPDs) is a challenge. Herein, we report a general method to prepare pink, blue, and yellow nanoparticles with low density and a tunable size of 230-310 nm. The monodispersity is down to 0.02 and surface charges are up to 666e. Importantly, our work highlights the feasibility of chromatic nanoparticles as cost-effective candidates for electrophoretic displays. PMID- 27189744 TI - Charge carrier kinetics of carbon nitride colloid: a femtosecond transient absorption spectroscopy study. AB - Carbon nitrides (CN) have been widely used in photocatalytic applications. However, the charge carrier kinetics of CN after light excitation remains unclear. Herein, we prepared a stable and transparent CN colloid in an aqueous tetraethylammonium hydroxide solution and investigated its carrier kinetics using both femtosecond transient absorption and picosecond time-resolved fluorescence spectroscopy. We found that a new and positive absorption band appears in the femtosecond transient absorption spectrum of the CN colloid, which could be attributed to the absorption of the photogenerated electron/hole pairs (or the electronic excited state) of the CN colloid after light excitation. Moreover, we found that the charge carrier kinetics obtained from the femtosecond transient absorption measurements is dramatically different from that obtained from the picosecond time-resolved fluorescence measurements, indicating that the photophysical process of the CN colloid after light excitation is complicated. With the results obtained from both the femtosecond transient absorption and picosecond time-resolved fluorescence measurements, we proposed a schematic to understand the photophysics and charge carrier kinetics of the CN colloid. We believe that the current study is also significant for researchers to understand the photophysics and charge carrier kinetics of bulk CN. PMID- 27189745 TI - Rapid Dihydrogen Cleavage by Persistent Nitroxide Radicals under Frustrated Lewis Pair Conditions. AB - Persistent radicals undergo hydrogen atom abstraction reactions with a great variety of substrates, but not with dihydrogen. It has now been found that the TEMPO radical splits dihydrogen under mild conditions in the presence of the strong bulky B(C6 F5 )3 boron Lewis acid. The reaction is thought to proceed by a typical frustrated Lewis pair mechanism with the TEMPO radical acting as the active Lewis base. The reaction was analyzed by DFT, which indicates that no significant spin density on the hydrogen atoms is accumulated along the H2 splitting reaction path. PMID- 27189747 TI - 2015 Articles of the Year, Reviewers of the Year, and Figure of the Year. PMID- 27189746 TI - High Resolution X-ray-Induced Acoustic Tomography. AB - Absorption based CT imaging has been an invaluable tool in medical diagnosis, biology, and materials science. However, CT requires a large set of projection data and high radiation dose to achieve superior image quality. In this letter, we report a new imaging modality, X-ray Induced Acoustic Tomography (XACT), which takes advantages of high sensitivity to X-ray absorption and high ultrasonic resolution in a single modality. A single projection X-ray exposure is sufficient to generate acoustic signals in 3D space because the X-ray generated acoustic waves are of a spherical nature and propagate in all directions from their point of generation. We demonstrate the successful reconstruction of gold fiducial markers with a spatial resolution of about 350 MUm. XACT reveals a new imaging mechanism and provides uncharted opportunities for structural determination with X-ray. PMID- 27189752 TI - Health workers should reverse FGM procedures by deinfibulation, WHO says. PMID- 27189753 TI - Risk-based approach to developing a national residue sampling plan for testing under European Union regulation for veterinary medicinal products and coccidiostat feed additives in domestic animal production. AB - A ranking system for veterinary medicinal products and coccidiostat feed additives has been developed as a tool to be applied in a risk-based approach to the residue testing programme for foods of animal origin in the Irish National Residue Control Plan (NRCP). Three characteristics of substances that may occur as residues in food are included in the developed risk ranking system: Potency, as measured by the acceptable daily intake assigned by the European Medicines Agency Committee for Medicinal Products for Veterinary Use, to each substance; Usage, as measured by the three factors of Number of Doses, use on Individual animals or for Group treatment, and Withdrawal Period; and Residue Occurrence, as measured by the number of Non-Compliant Samples in the NRCP. For both Number of Doses and Non-Compliant Samples, data for the 5-year period 2008-12 have been used. The risk ranking system for substances was developed for beef cattle, sheep and goats, pigs, chickens and dairy cattle using a scoring system applied to the various parameters described above to give an overall score based on the following equation: Potency * Usage (Number of Doses + Individual/Group Use + Withdrawal Period) * Residue Occurrence. Applying this risk ranking system, the following substances are ranked very highly: antimicrobials such as amoxicillin (for all species except pigs), marbofloxacillin (for beef cattle), oxytetracycline (for all species except chickens), sulfadiazine with trimethoprim (for pigs and chickens) and tilmicosin (for chickens); antiparasitic drugs, such as the benzimidazoles triclabendazole (for beef and dairy cattle), fenbendazole/oxfendazole (for sheep/goats and dairy cattle) and albendazole (for dairy cattle), the avermectin ivermectin (for beef cattle), and anti-fluke drugs closantel and rafoxanide (for sheep/goats); the anticoccidials monensin, narasin, nicarbazin and toltrazuril (for chickens). The risk ranking system described is a relatively simple system designed to provide a reliable basis for selecting the veterinary medicinal products and coccidiostat feed additives that might be prioritised for residue testing. PMID- 27189756 TI - Ferroptosis, a newly characterized form of cell death in Parkinson's disease that is regulated by PKC. AB - Parkinson's disease (PD) is a complex illness characterized by progressive dopaminergic neuronal loss. Several mechanisms associated with the iron-induced death of dopaminergic cells have been described. Ferroptosis is an iron dependent, regulated cell death process that was recently described in cancer. Our present work show that ferroptosis is an important cell death pathway for dopaminergic neurons. Ferroptosis was characterized in Lund human mesencephalic cells and then confirmed ex vivo (in organotypic slice cultures) and in vivo (in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model). Some of the observed characteristics of ferroptosis differed from those reported previously. For example, ferroptosis may be initiated by PKCalpha activation, which then activates MEK in a RAS-independent manner. The present study is the first to emphasize the importance of ferroptosis dysregulation in PD. In neurodegenerative diseases like PD, iron chelators, Fer-1 derivatives and PKC inhibitors may be strong drug candidates to pharmacologically modulate the ferroptotic signaling cascade. PMID- 27189757 TI - Triethyl orthoformate covalently cross-linked chitosan-(poly vinyl) alcohol based biodegradable scaffolds with heparin-binding ability for promoting neovascularisation. AB - There is a need to develop pro-angiogenic biomaterials to promote wound healing and to assist in regenerative medicine. To this end, various growth factors have been exploited which have the potential to promote angiogenesis. However, these are generally expensive and labile which limits their effectiveness. An alternative approach is to immobilize heparin onto biocompatible degradable hydrogels. The heparin in turn will then bind endogenous proangiogenic growth factors to induce formation of new blood vessels.In this study, we continue our development of hydrogels for wound healing purposes by exploring covalently cross linking chitosan and polyvinyl alcohol hydrogels using triethyl orthoformate. Two concentrations of triethyl orthoformate (4 and 16%) were compared for their effects on the structure of hydrogels - their swelling, pore size, and rate of degradation and for their ability to support the growth of cells and for their heparin-binding capacity and their effects on angiogenesis in a chick chorioallantoic membrane assay.Hydrogels formed with 4 or 16% both triethyl orthoformate cross-linker were equally cyto-compatible. Hydrogels formed with 4% triethyl orthoformate absorbed slightly more water than those made with 16% triethyl orthoformate and broke down slightly faster than non-cross-linked hydrogels. When soaked in heparin the hydrogel formed with 16% triethyl orthoformate showed more blood vessel formation in the CAM assay than that formed with 4% triethyl orthoformate. PMID- 27189754 TI - 22q11.2 deletion syndrome. AB - 22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal microdeletion disorder, estimated to result mainly from de novo non-homologous meiotic recombination events occurring in approximately 1 in every 1,000 fetuses. The first description in the English language of the constellation of findings now known to be due to this chromosomal difference was made in the 1960s in children with DiGeorge syndrome, who presented with the clinical triad of immunodeficiency, hypoparathyroidism and congenital heart disease. The syndrome is now known to have a heterogeneous presentation that includes multiple additional congenital anomalies and later-onset conditions, such as palatal, gastrointestinal and renal abnormalities, autoimmune disease, variable cognitive delays, behavioural phenotypes and psychiatric illness - all far extending the original description of DiGeorge syndrome. Management requires a multidisciplinary approach involving paediatrics, general medicine, surgery, psychiatry, psychology, interventional therapies (physical, occupational, speech, language and behavioural) and genetic counselling. Although common, lack of recognition of the condition and/or lack of familiarity with genetic testing methods, together with the wide variability of clinical presentation, delays diagnosis. Early diagnosis, preferably prenatally or neonatally, could improve outcomes, thus stressing the importance of universal screening. Equally important, 22q11.2DS has become a model for understanding rare and frequent congenital anomalies, medical conditions, psychiatric and developmental disorders, and may provide a platform to better understand these disorders while affording opportunities for translational strategies across the lifespan for both patients with 22q11.2DS and those with these associated features in the general population. PMID- 27189758 TI - Developing a classification system of social communication functioning of preschool children with autism spectrum disorder. AB - AIM: Impairments in social communication are the hallmark of autism spectrum disorder (ASD). Operationalizing 'severity' in ASD has been challenging; thus, stratifying by functioning has not been possible. The purpose of this study is to describe the development of the Autism Classification System of Functioning: Social Communication (ACSF:SC) and to evaluate its consistency within and between parent and professional ratings. METHOD: (1) ACSF:SC development based on focus groups and surveys involving parents, educators, and clinicians familiar with preschoolers with ASD; and (2) evaluation of the intra- and interrater agreement of the ACSF:SC using weighted kappa (kw ). RESULTS: Seventy-six participants were involved in the development process. Core characteristics of social communication were ascertained: communicative intent; communicative skills and reciprocity; and impact of environment. Five ACSF:SC levels were created and content-validated across participants. Best capacity and typical performance agreement ratings varied as follows: intrarater agreement on 41 children was kw =0.61 to 0.69 for parents, and kw =0.71 to 0.95 for professionals; interrater agreement between professionals was kw =0.47 to 0.61, and between parents and professionals was kw =0.33 to 0.53. INTERPRETATION: Perspectives from parents and professionals informed ACSF:SC development, providing common descriptions of the levels of everyday communicative abilities of children with ASD to complement the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Rater agreement demonstrates that the ACSF:SC can be used with acceptable consistency compared with other functional classification systems. PMID- 27189760 TI - Function of Thymosin Beta-4 in Ethanol-Induced Microglial Activation. AB - BACKGROUND/AIMS: Neuroinflammation mediated by activated microglia may play a pivotal role in a variety of central nervous system (CNS) pathologic conditions, including ethanol-induced neurotoxicity. The purpose of this study was to investigate the function of Tbeta4 in ethanol-induced microglia activation. METHODS: Quantitative real-time PCR was conducted to assess the expression of Tbeta4 and miR-339-5p. Western blot analysis was used to measure the expression of Tbeta4, phosphorylated p38, ERK, JNK, Akt, and NF-x03BA;B p65. The concentration of TNF-alpha and IL-1beta was determined using ELISA. NO concentration was measured using a nitric oxide colorimetric BioAssay Kit. Double immunofluorescence was performed to determine Tbeta4 expression, in order to assess microglial activation in neonatal mouse FASD model. RESULTS: Increased Tbeta4 expression was observed in ethanol treated microglia. Knockdown of Tbeta4 enhanced ethanol-induced inflammatory mediators tumor necrosis factor-alpha (TNF alpha) and interleukin-1beta (IL-1beta) and nitric oxide (NO) in BV-2 cells was performed. Exogenous Tbeta4 treatment significantly inhibited expression and secretion of these inflammatory mediators. Tbeta4 treatment attenuated p38, ERK MAPKs, and nuclear factor-kappa B (NF-x03BA;B) pathway activation, and enhanced miR-339-5p expression induced by ethanol exposure in microglia. A neonatal mouse fetal alcohol spectrum disorders (FASD) model showed that Tbeta4 expression in the microglia of the hippocampus was markedly enhanced, while Tbeta4 treatment effectively blocked the ethanol-induced increase in inflammatory mediators, to the level expressed in vehicle-treated control animals. CONCLUSION: This study is the first to demonstrate the function of Tbeta4 in ethanol-induced microglia activation, thus contributing to a more robust understanding of the role of Tbeta4 treatment in CNS disease. PMID- 27189759 TI - Retargeting FX-binding-ablated HAdV-5 to vascular cells by inclusion of the RGD 4C peptide in hexon hypervariable region 7 and the HI loop. AB - Recent studies have generated interest in the function of human adenovirus serotype 5 (HAdV-5) hexon: factor X (FX) binding and subsequent hepatocyte transduction and interaction with the immune system. Here, we retargeted adenovirus serotype 5 vectors, ablated for FX interaction, by replacing amino acids in hexon HVR7 with RGD-4C or inserting the peptide into the fibre HI loop. These genetic modifications in the capsid were compatible with virus assembly, and could efficiently retarget transduction of the vector via the alphavbeta3/5 integrin-mediated pathway, but did not alter immune recognition by pre-existing human neutralizing anti-HAdV-5 antibodies or by natural antibodies in mouse serum. Thus, FX-binding-ablated HAdV-5 can be retargeted but remain sensitive to immune-mediated attack. These findings further refine HAdV-5-based vectors for human gene therapy and inform future vector development. PMID- 27189755 TI - Update of neurotrophic factors in neurobiology of addiction and future directions. AB - Drug addiction is a chronic brain disease and drugs of abuse cause long lasting neuroadaptations. Addiction is characterized by the loss of control over drug use despite harmful consequences, and high rates of relapse even after long periods of abstinence. Neurotrophic factors (NTFs) are well known for their actions on neuronal survival in the peripheral nervous system. Moreover, NTFs have been shown to be involved in synaptic plasticity in the brain. Brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) are two of the most studied NTFs and both of them have been reported to increase craving when administered into the mesocorticolimbic dopaminergic system after drug self-administration. Here we review recent data on BDNF and GDNF functions in addiction-related behavior and discuss them in relation to previous findings. Finally, we give an insight into how new technologies could aid in further elucidating the role of these factors in drug addiction. PMID- 27189761 TI - Genetics of Type 2 Diabetes: the Power of Isolated Populations. AB - Type 2 diabetes (T2D) affects millions of people worldwide. Improving the understanding of the underlying mechanisms and ultimately improving the treatment strategies are, thus, of great interest. To achieve this, identification of genetic variation predisposing to T2D is important. A large number of variants have been identified in large outbred populations, mainly from Europe and Asia. However, to elucidate additional variation, isolated populations have a number of advantageous properties, including increased amounts of linkage disequilibrium, and increased probability for presence of high frequency disease-associated variants due to genetic drift. Collectively, this increases the statistical power to detect association signals in isolated populations compared to large outbred populations. In this review, we elaborate on why isolated populations are a powerful resource for the identification of complex disease variants and describe their contributions to the understanding of the genetics of T2D. PMID- 27189765 TI - The structural and dynamical aspects of boron nitride nanotubes under high velocity impacts. AB - This communication report is a study on the structural and dynamical aspects of boron nitride nanotubes (BNNTs) shot at high velocities (~5 km s(-1)) against solid targets. The experimental results show unzipping of BNNTs and the formation of hBN nanoribbons. Fully atomistic reactive molecular dynamics simulations were also carried out to gain insights into the BNNT fracture patterns and deformation mechanisms. Our results show that longitudinal and axial tube fractures occur, but the formation of BN nanoribbons from fractured tubes was only observed for some impact angles. Although some structural and dynamical features of the impacts are similar to the ones reported for CNTs, because BNNTs are more brittle than CNTs this results in a larger number of fractured tubes but with fewer formed nanoribbons. PMID- 27189764 TI - Involvement of nigral oxytocin in locomotor activity: A behavioral, immunohistochemical and lesion study in male rats. AB - Oxytocin is involved in the control of different behaviors, from sexual behavior and food consumption to empathy, social and affective behaviors. An imbalance of central oxytocinergic neurotransmission has been also associated with different mental pathologies, from depression, anxiety and anorexia/bulimia to schizophrenia, autism and drug dependence. This study shows that oxytocin may also play a role in the control of locomotor activity. Accordingly, intraperitoneal oxytocin (0.5-2000MUg/kg) reduced locomotor activity of adult male rats. This effect was abolished by d(CH2)5Tyr(Me)(2)-Orn(8)-vasotocin, an oxytocin receptor antagonist, given into the lateral ventricles at the dose of 2MUg/rat, which was ineffective on locomotor activity. Oxytocin (50-200ng/site) also reduced and d(CH2)5Tyr(Me)(2)-Orn(8)-vasotocin (2MUg/site) increased locomotor activity when injected bilaterally into the substantia nigra, a key area in the control of locomotor activity. Conversely, the destruction of nigral neurons bearing oxytocin receptors by the recently characterized neurotoxin oxytocin-saporin injected into the substantia nigra, increased basal locomotor activity. Since oxytocin-saporin injected into the substantia nigra caused a marked reduction of neurons immunoreactive for tyrosine hydroxylase (e.g., nigrostriatal dopaminergic neurons) and for vesicular glutamate transporters VGluT1, VGluT2 and VGluT3 (e.g., glutamatergic neurons), but not for glutamic acid decarboxylase (e.g., GABAergic neurons), together these findings suggest that oxytocin influences locomotor activity by acting on receptors localized presynaptically in nigral glutamatergic nerve terminals (which control the activity of nigral GABAergic efferent neurons projecting to brain stem nuclei controlling locomotor activity), rather than on receptors localized in the cell bodies/dendrites of nigrostriatal dopaminergic neurons. PMID- 27189763 TI - Elevated corticosterone during egg production elicits increased maternal investment and promotes nestling growth in a wild songbird. AB - Glucocorticoids circulating in breeding birds during egg production accumulate within eggs, and may provide a potent form of maternal effect on offspring phenotype. However, whether these steroids affect offspring development remains unclear. Here, we employed a non-invasive technique that experimentally elevated the maternal transfer of corticosterone to eggs in a wild population of house wrens. Feeding corticosterone-injected mealworms to free-living females prior to and during egg production increased the number of eggs that females produced and increased corticosterone concentrations in egg yolks. This treatment also resulted in an increase in the amount of yolk allocated to eggs. Offspring hatching from these eggs begged for food at a higher rate than control offspring and eventually attained increased prefledging body condition, a trait predictive of their probability of recruitment as breeding adults in the study population. Our results indicate that an increase in maternal glucocorticoids within the physiological range can enhance maternal investment and offspring development. PMID- 27189762 TI - Non-ovarian aromatization is required to activate female sexual motivation in testosterone-treated ovariectomized quail. AB - Although aromatase is expressed in both male and female brains, its functional significance in females remains poorly understood. In female quail, sexual receptivity is activated by estrogens. However it is not known whether sexual motivation is similarly estrogen-dependent and whether estrogens locally produced in the brain contribute to these behavioral responses. Four main experiments were designed to address these questions. In Experiment 1 chronic treatment of females with the anti-estrogen tamoxifen decreased their receptivity, confirming that this response is under the control of estrogens. In Experiment 2 chronic treatment with tamoxifen significantly decreased sexual motivation as treated females no longer approached a sexual partner. In Experiment 3 (a) ovariectomy (OVX) induced a significant decrease of time spent near the male and a significantly decreased receptivity compared to gonadally intact females, (b) treatment with testosterone (OVX+T) partially restored these responses and (c) this effect of T was prevented when estradiol synthesis was inhibited by the potent aromatase inhibitor Vorozole (OVX+T+VOR). Serum estradiol concentration was significantly higher in OVX+T than in OVX or OVX+T+VOR females. Together these data demonstrate that treatment of OVX females with T increases sexual motivation and that these effects are mediated at least in part by non-gonadal aromatization of the androgen. Finally, assays of aromatase activity on brain and peripheral tissues (Experiment 4) strongly suggest that brain aromatization contributes to behavioral effects observed here following T treatment but alternative sources of estrogens (e.g. liver) should also be considered. PMID- 27189767 TI - Anatomic features of the distal aortic arch that influence endovascular aneurysm repair. AB - OBJECTIVE: Successful thoracic endovascular aneurysm repair (TEVAR) is contingent on seal and fixation of the proximal graft. The aortic arch has a wide range of anatomic variability, and understanding that anatomy may optimize device deployment. The purpose of this study was to assess aortic arch anatomic features that influence zones 2 and 3 TEVAR and specifically to quantitate the impact of gantry angle correction on proximal seal zone for patients with proximal descending thoracic aortic disease. METHODS: Sixty patients with descending thoracic aortic pathology that would require TEVAR with a zone 2 or 3 deployment were evaluated. Demographic and imaging data were retrospectively reviewed. Computed tomography scans were evaluated using a 3-dimensional workstation for centerline and angle analyses. The optimal gantry angle was determined to be the orthogonal view of the leading (proximal) edge of the seal zone based on a manual adjusted centerline. Measurements were then taken of the seal zone at -10 degrees and -20 degrees from optimal view to assess the impact of imperfect gantry angle correction. RESULTS: The study included 38 men (63%) with a mean age of 66 years (range, 24-90 years). Thirty-eight (63%) required zone 2 deployment. Zone 2 seal zones were shorter and required less gantry angulation for an optimal view than were zone 3 seal zones. Incomplete gantry angle correction affected expected use of both zone 2 and 3 seal zones similarly. At 10 degrees and 20 degrees from optimal gantry angel, the loss in use of available seal zone length is estimated to be 2.4 +/- 1.1 and 6.2 +/- 2.3 mm, or 10% and 25%, respectively. These results were not different for men or women, nor were they influenced by age, sex, body mass index, height, or etiology of aortic pathology. Inner and outer curvature measurements differed by 80%. Only four patients (7%) had a zone 1 segment >= 5 mm in length. CONCLUSIONS: Optimal gantry angle correction should be the goal of any TEVAR procedure. Zone 2 seal zones require less gantry angulation than zone 3 seal zones by nearly 20 degrees . This study shows that correction within 10 degrees of optimal is unlikely to significantly impact successful seal and fixation for most patients. At 20 degrees , however, substantial loss of seal zone can be expected. Measurements of the inner and outer curvature reveal different information about the distal arch and should be assessed individually. Zone 1 deployment rarely provides meaningful additional seal zone length. PMID- 27189766 TI - Primary closure after carotid endarterectomy is not inferior to other closure techniques. AB - OBJECTIVE: Primary closure after carotid endarterectomy (CEA) has been much maligned as an inferior technique with worse outcomes than in patch closure. Our purpose was to compare perioperative and long-term results of different CEA closure techniques in a large institutional experience. METHODS: A consecutive cohort of CEAs between January 1, 2000, and December 31, 2010, was retrospectively analyzed. Closure technique was used to divide patients into three groups: primary longitudinal arteriotomy closure (PRC), patch closure (PAC), and eversion closure (EVC). End points were perioperative events, long term strokes, and restenosis >=70%. Multivariate regression models were used to assess the effect of baseline predictors. RESULTS: There were 1737 CEA cases (bilateral, 143; mean age, 71.4 +/- 9.3 years; 56.2% men; 35.3% symptomatic) performed during the study period with a mean clinical follow-up of 49.8 +/- 36.4 months (range, 0-155 months). More men had primary closure, but other demographic and baseline symptoms were similar between groups. Half the patients had PAC, with the rest evenly distributed between PRC and EVC. The rate of nerve injury was 2.7%, the rate of reintervention for hematoma was 1.5%, and the length of hospital stay was 2.4 +/- 3.0 days, with no significant differences among groups. The combined stroke and death rate was 2.5% overall and 3.9% and 1.7% in the symptomatic and asymptomatic cohort, respectively. Stroke and death rates were similar between groups: PRC, 11 (2.7%); PAC, 19 (2.2%); EVC, 13 (2.9%). Multivariate analysis showed baseline symptomatic disease (odds ratio, 2.4; P = .007) and heart failure (odds ratio, 3.1; P = .003) as predictors of perioperative stroke and death, but not the type of closure. Cox regression analysis demonstrated, among other risk factors, no statin use (hazard ratio, 2.1; P = .008) as a predictor of ipsilateral stroke and severe (glomerular filtration rate <30 mL/min/1.73 m(2)) renal insufficiency (hazard ratio, 2.6; P = .032) as the only predictor of restenosis >=70%. Type of closure did not have any predictive value. CONCLUSIONS: In our study, baseline risk factors and statin use, but not the type of closure, affect perioperative and long-term outcomes after CEA. PMID- 27189768 TI - Failure mode analysis of the Endologix endograft. AB - OBJECTIVE: Type III (T-III) endoleaks following endovascular aneurysm repair (EVAR) remain a major concern. Our center experienced a recent concentration of T III endoleaks requiring elective and emergency treatment and prompted our review of all EVAR implants over a 40-month period from April 2011 until August 2014. This report represents a single center experience with T-III endoleak management with analysis of factors leading to the T-III-related failure of EVAR. METHODS: A retrospective review of all the operative reports, medical records, and computed tomography scans were reviewed from practice surveillance. Using Society for Vascular Surgery aneurysm reporting standards, we analyzed the morphology of the aneurysms before and after EVAR implant using computed tomography. Index procedure and frequency of reinterventions required to maintain aneurysm freedom from rupture were compared across all devices using SAS v 9.4 (SAS Institute, Inc, Cary, NC). Major adverse events (MAEs) requiring secondary interventions for aneurysm treatment beyond primary implant were analyzed for methods of failure. Aneurysm morphology of patients requiring EVAR was compared across all endograft devices used for repair. For purposes of MAE analysis, patients receiving Endologix (ELX) endograft were combined into group 1; Gore, Cook, and Medtronic endograft patients were placed into group 2. RESULTS: Overall, technical success and discharge survival were achieved in 97.3% and 98% of patients regardless of device usage. There was no significant device related difference identified between patient survival or freedom from intervention. MAEs involving aneurysm treatment were over seven-fold more frequent with ELX (group 1) vs non-ELX (group 2) endografts (P < .01). Group 1 patients with aneurysm diameters larger than 65 mm were associated with a highly significant value for development of a T-III endoleak (odds ratio, 11.16; 95% confidence interval, 2.17, 57.27; P = .0038). CONCLUSIONS: While EVAR technical success and survival were similar across all devices, ELX devices exhibited an unusually high incidence of T-III endoleaks when implanted in abdominal aortic aneurysms with a diameter of more than 65 mm. Frequent reinterventions were required for Endologix devices for prevention of aneurysm rupture due to T-III endoleaks. PMID- 27189769 TI - Outcomes after retroflexed gracilis muscle flap for vascular infections in the groin. AB - OBJECTIVE: Multiple catheterizations and procedures on the femoral arteries can increase the risk of infection and eventual destruction of the overlying skin and subcutaneous tissue. Without adequate tissue coverage, vascular structures are exposed and, thus, vulnerable to disruption. This can lead to loss of limb and/or life and carries a significant mortality. We hypothesized that gracilis muscle flap (GMF) was a reliable adjunct in providing healthy tissue coverage for a complex surgical problem. METHODS: Retrospective review of charts was performed on all patients who had undergone GMF for groin infections at a tertiary care medical center. RESULTS: From 1997 to 2012, GMF was performed in 68 limbs (64 patients) by vascular surgeons for infectious etiology to cover the common femoral artery. At the time the GMF was placed, the femoral artery had synthetic graft/patch in 14 limbs, whereas 54 limbs had procedures with autologous conduit. Complete healing was achieved in 58 (85%) limbs. Treatment was deemed not successful in 10 limbs where patients continued to have persistent infection. Six out of 10 limbs had anastomosis disruption requiring emergent ligation of the common femoral artery. Nine patients died during the perioperative period (30 day). There were a total of 13 amputations in 12 patients. Limb salvage was achieved in 55 limbs (81%). Univariate analysis suggested that patients that had revascularization procedures with synthetic graft had a higher complication rate compared with autologous/vein reconstruction (24% vs 5%; P = .021). This group also has a higher rate of persistent infection compared with the autologous group (24% vs 2%; P = .006). Patients older than 75 years at the time of GMF had a higher incidence of GMF-related complications (57% vs 5%; P = .04). Multivariate analysis confirmed that presence of prosthesis led to higher incidence treatment failures and muscle flap complications at the surgical site (odds ratio, 6.6; P = .04; and odds ratio, 13.3; P = .03, respectively). CONCLUSIONS: GMF is technically simple to perform and provides durable soft tissue coverage with a high rate of healing for complex groin wounds even in the presence of synthetic conduit. PMID- 27189770 TI - Mortality rates and walking ability transition after lower limb major amputation in hemodialysis patients. AB - OBJECTIVE: The number of hemodialysis patients with peripheral artery disease is increasing, and critical limb ischemia develops in some of these patients. The clinical outcomes in such patients after major amputation remain unclear. We therefore examined the mortality rates after major amputation in hemodialysis patients. METHODS: The study enrolled 108 hemodialysis patients undergoing their first major amputation at Community Health Care Organization Sendai Hospital between January 2005 and December 2014 and monitored them until June 2015. All cause mortality and additional amputation-free survival were evaluated by Kaplan Meier analysis. RESULTS: The most dominant primary disease of renal failure was diabetes mellitus (77%), and the duration of hemodialysis was 8.5 +/- 6.8 years. During the median follow-up period of 11.5 months (20.3 +/- 22.6 months), 80 patients (74%) died, and the survival rates were 83% at 30 days, 56% at 1 year, and 15% at 5 years. The median time to death was 19.9 months (95% confidence interval, 9.8-30.0 months), and the causes of death were cardiac (45%), sepsis (29%), cerebrovascular (4%), and others (22%). Thirty-one patients underwent additional amputation, and the additional amputation-free survival rates were 39% at 1 year and 9% at 5 years. The median time between the first and second amputations was 2.5 months (5.7 +/- 7.6 months). Univariate analysis showed previous minor amputation (P = .04) and low hematocrit level (P = .04) were associated with the 30-day mortality rate, and age (P = .05) was associated with the 5-year mortality rate. On multivariate Cox proportional hazard analysis, only age was associated with mortality rate (hazard ratio, 1.02; 95% confidence interval, 0.99-1.02; P = .04). We also compared walking ability before and after major amputation among patients who survived >60 days. The rate changed from 34% to 12% for of ambulatory patients, from 45% to 48% for wheelchair use, and from 21% to 40% for bedridden patients. Ambulatory patients had a significantly better survival rate than the others (P = .02). CONCLUSIONS: The mortality rate after major amputation in hemodialysis patients was high, and major amputation had a huge negative effect on patients' walking ability. PMID- 27189771 TI - HIV infection results in metabolic alterations in the gut microbiota different from those induced by other diseases. AB - Imbalances in gut bacteria have been associated with multiple diseases. However, whether there are disease-specific changes in gut microbial metabolism remains unknown. Here, we demonstrate that human immunodeficiency virus (HIV) infection (n = 33) changes, at quantifiable levels, the metabolism of gut bacteria. These changes are different than those observed in patients with the auto-immune disease systemic lupus erythaematosus (n = 18), and Clostridium difficile associated diarrhoea (n = 6). Using healthy controls as a baseline (n = 16), we demonstrate that a trend in the nature and directionality of the metabolic changes exists according to the type of the disease. The impact on the gut microbial activity, and thus the metabolite composition and metabolic flux of gut microbes, is therefore disease-dependent. Our data further provide experimental evidence that HIV infection drastically changed the microbial community, and the species responsible for the metabolism of 4 amino acids, in contrast to patients with the other two diseases and healthy controls. The identification in this present work of specific metabolic deficits in HIV-infected patients may define nutritional supplements to improve the health of these patients. PMID- 27189772 TI - Validation of a new measure of availability and accommodation of health care that is valid for rural and urban contexts. AB - CONTEXT: Patients are the most valid source for evaluating the accessibility of services, but a previous study observed differential psychometric performance of instruments in rural and urban respondents. OBJECTIVE: To validate a measure of organizational accessibility free of differential rural-urban performance that predicts consequences of difficult access for patient-initiated care. DESIGN: Sequential qualitative-quantitative study. Qualitative findings used to adapt or develop evaluative and reporting items. Quantitative validation study. SETTING: Primary data by telephone from 750 urban, rural and remote respondents in Quebec, Canada; follow-up mailed questionnaire to a subset of 316. MAIN MEASURES AND ANALYSES: Items were developed for barriers along the care trajectory. We used common factor and confirmatory factor analysis to identify constructs and compare models. We used item response theory analysis to test for differential rural urban performance; examine individual item performance; adjust response options; and exclude redundant or non-discriminatory items. We used logistic regression to examine predictive validity of the subscale on access difficulty (outcome). RESULTS: Initial factor resolution suggested geographic and organizational dimensions, plus consequences of access difficulty. After second administration, organizational accommodation and geographic indicators were integrated into a 6 item subscale of Effective Availability and Accommodation, which demonstrates good variability and internal consistency (alpha = 0.84) and no differential functioning by geographic area. Each unit increase predicts decreased likelihood of consequences of access difficulties (unmet need and problem aggravation). CONCLUSION: The new subscale is a practical, valid and reliable measure for patients to evaluate first-contact health services accessibility, yielding valid comparisons between urban and rural contexts. PMID- 27189773 TI - Mental health nurses' experiences of managing work-related emotions through supervision. AB - AIM: The aim of this study was to explore emotion cultures constructed in supervision and consider how supervision functions as an emotionally safe space promoting critical reflection. BACKGROUND: Research published between 1995-2015 suggests supervision has a positive impact on nurses' emotional well-being, but there is little understanding of the processes involved in this and how styles of emotion interaction are established in supervision. DESIGN: A narrative approach was used to investigate mental health nurses' understandings and experiences of supervision. METHODS: Eight semi-structured interviews were conducted with community mental health nurses in the UK during 2011. Analysis of audio data used features of speech to identify narrative discourse and illuminate meanings. A topic-centred analysis of interview narratives explored discourses shared between the participants. This supported the identification of feeling rules in participants' narratives and the exploration of the emotion context of supervision. FINDINGS: Effective supervision was associated with three feeling rules: safety and reflexivity; staying professional; managing feelings. These feeling rules allowed the expression and exploration of emotions, promoting critical reflection. A contrast was identified between the emotion culture of supervision and the nurses' experience of their workplace cultures as requiring the suppression of difficult emotions. Despite this, contrast supervision functioned as an emotion micro-culture with its own distinctive feeling rules. CONCLUSIONS: The analytical construct of feeling rules allows us to connect individual emotional experiences to shared normative discourses, highlighting how these shape emotional processes taking place in supervision. This understanding supports an explanation of how supervision may positively influence nurses' emotion management and perhaps reduce burnout. PMID- 27189774 TI - Zolpidem Mucoadhesive Formulations for Intranasal Delivery: Characterization, In Vitro Permeability, Pharmacokinetics, and Nasal Ciliotoxicity in Rats. AB - Zolpidem is a non-benzodiazepine hypnotic for the treatment of insomnia characterized by difficulties with sleep initiation. Our study aimed at developing a zolpidem mucoadhesive formulation with minimal local toxicity, prolonged nasal residence time, and enhanced absorption after intranasal delivery. In vitro permeability studies using artificial membrane and Calu-3 cell culture model indicated efficient permeability of zolpidem. Aqueous solubility of zolpidem was found to be significantly improved by hydroxypropyl-beta cyclodextrin. Various mucoadhesive formulations were then prepared comprising zolpidem, hydroxypropyl-beta-cyclodextrin, and mucoadhesive polymers such as hydroxypropyl methylcellulose, sodium carboxymethylcellulose, and sodium alginate. Pharmacokinetic studies in rats demonstrated that intranasally administered zolpidem could achieve significantly faster absorption rate and higher plasma concentration than that from oral route. In comparison with solution formulation (ZLP-S03), the optimized mucoadhesive formulation (ZLP-B01) containing 0.25% hydroxypropyl methylcellulose was found to improve Cmax from 352.6 +/- 86.0 to 555.7 +/- 175.8 ng/mL, and AUC0-inf from 32,890 +/- 7547 to 65,447 +/- 36,996 ng.min/mL with mild nasal ciliotoxicity in rats. PMID- 27189775 TI - A novel pathway for fungal D-glucuronate catabolism contains an L-idonate forming 2-keto-L-gulonate reductase. AB - For the catabolism of D-glucuronate, different pathways are used by different life forms. The pathways in bacteria and animals are established, however, a fungal pathway has not been described. In this communication, we describe an enzyme that is essential for D-glucuronate catabolism in the filamentous fungus Aspergillus niger. The enzyme has an NADH dependent 2-keto-L-gulonate reductase activity forming L-idonate. The deletion of the corresponding gene, the gluC, results in a phenotype of no growth on D-glucuronate. The open reading frame of the A. niger 2-keto-L-gulonate reductase was expressed as an active protein in the yeast Saccharomyces cerevisiae. A histidine tagged protein was purified and it was demonstrated that the enzyme converts 2-keto-L-gulonate to L-idonate and, in the reverse direction, L-idonate to 2-keto-L-gulonate using the NAD(H) as cofactors. Such an L-idonate forming 2-keto-L-gulonate dehydrogenase has not been described previously. In addition, the finding indicates that the catabolic D glucuronate pathway in A. niger differs fundamentally from the other known D glucuronate pathways. PMID- 27189776 TI - Cotton-textile-enabled flexible self-sustaining power packs via roll-to-roll fabrication. AB - With rising energy concerns, efficient energy conversion and storage devices are required to provide a sustainable, green energy supply. Solar cells hold promise as energy conversion devices due to their utilization of readily accessible solar energy; however, the output of solar cells can be non-continuous and unstable. Therefore, it is necessary to combine solar cells with compatible energy storage devices to realize a stable power supply. To this end, supercapacitors, highly efficient energy storage devices, can be integrated with solar cells to mitigate the power fluctuations. Here, we report on the development of a solar cell supercapacitor hybrid device as a solution to this energy requirement. A high performance, cotton-textile-enabled asymmetric supercapacitor is integrated with a flexible solar cell via a scalable roll-to-roll manufacturing approach to fabricate a self-sustaining power pack, demonstrating its potential to continuously power future electronic devices. PMID- 27189777 TI - Automated integer programming based separation of arteries and veins from thoracic CT images. AB - Automated computer-aided analysis of lung vessels has shown to yield promising results for non-invasive diagnosis of lung diseases. To detect vascular changes which affect pulmonary arteries and veins differently, both compartments need to be identified. We present a novel, fully automatic method that separates arteries and veins in thoracic computed tomography images, by combining local as well as global properties of pulmonary vessels. We split the problem into two parts: the extraction of multiple distinct vessel subtrees, and their subsequent labeling into arteries and veins. Subtree extraction is performed with an integer program (IP), based on local vessel geometry. As naively solving this IP is time consuming, we show how to drastically reduce computational effort by reformulating it as a Markov Random Field. Afterwards, each subtree is labeled as either arterial or venous by a second IP, using two anatomical properties of pulmonary vessels: the uniform distribution of arteries and veins, and the parallel configuration and close proximity of arteries and bronchi. We evaluate algorithm performance by comparing the results with 25 voxel-based manual reference segmentations. On this dataset, we show good performance of the subtree extraction, consisting of very few non-vascular structures (median value: 0.9%) and merged subtrees (median value: 0.6%). The resulting separation of arteries and veins achieves a median voxel-based overlap of 96.3% with the manual reference segmentations, outperforming a state-of-the-art interactive method. In conclusion, our novel approach provides an opportunity to become an integral part of computer aided pulmonary diagnosis, where artery/vein separation is important. PMID- 27189778 TI - The assessment of adipocere to estimate the post-mortem interval - a skeleton from the tidelands. AB - SUMMARY: This paper discusses the discovery of a skeletonized water corpse with hollow bones filled with adipocere found in the tidelands of the river Elbe close to Otterndorf (Wesermarsch, Cuxhaven). Through macroscopic and microscopic methods, the existing adipocere was described. The post-mortem interval was assessed by a comparison of the radiocarbon data and the indications about the preservation of adipocere from the literature. The investigation has shown that the knowledge of post-mortem changes in adipocere within bone structures is still incomplete, especially for the assessment of water corpses with long post-mortem intervals. PMID- 27189779 TI - Insomnia disorder. AB - Insomnia disorder affects a large proportion of the population on a situational, recurrent or chronic basis and is among the most common complaints in medical practice. The disorder is predominantly characterized by dissatisfaction with sleep duration or quality and difficulties initiating or maintaining sleep, along with substantial distress and impairments of daytime functioning. It can present as the chief complaint or, more often, co-occurs with other medical or psychiatric disorders, such as pain and depression. Persistent insomnia has been linked with adverse long-term health outcomes, including diminished quality of life and physical and psychological morbidity. Despite its high prevalence and burden, the aetiology and pathophysiology of insomnia is poorly understood. In the past decade, important changes in classification and diagnostic paradigms have instigated a move from a purely symptom-based conceptualization to the recognition of insomnia as a disorder in its own right. These changes have been paralleled by key advances in therapy, with generic pharmacological and psychological interventions being increasingly replaced by approaches that have sleep-specific and insomnia-specific therapeutic targets. Psychological and pharmacological therapies effectively reduce the time it takes to fall asleep and the time spent awake after sleep onset, and produce a modest increase in total sleep time; these are outcomes that correlate with improvements in daytime functioning. Despite this progress, several challenges remain, including the need to improve our knowledge of the mechanisms that underlie insomnia and to develop more cost-effective, efficient and accessible therapies. PMID- 27189781 TI - Social support coping style predicts women's cortisol in the laboratory and daily life: the moderating role of social attentional biases. AB - BACKGROUND AND OBJECTIVES: Social stress and associated coping responses can profoundly influence women's stress physiology and health. Implicit social attentional biases can also influence psychological and physiological stress responses. The purpose of this study was to explore whether a coping style characterized by greater use of social support predicts indices of cortisol activity in laboratory and daily life contexts among female university students. We hypothesized that the relation of this coping style to cortisol activity would be moderated by women's attentional biases. METHODS: Seventy-four women (Mage = 19.44, range: 17.8-27.8, 64% White) completed an interpersonal stress task and an attentional bias task in the lab, along with a self-report coping inventory. Participants provided five saliva samples during the lab protocol, followed by three saliva samples per day for three consecutive weekdays. Outcome measures included cortisol response to lab tasks (AUCg), diurnal cortisol slope, diurnal AUCg, and cortisol awakening response (CARi). RESULTS: A coping style characterized by greater use of social support predicted lower lab AUCg and lower, flatter average diurnal cortisol slope for women with attentional avoidance compared to women with attentional vigilance (ps < .05). CONCLUSIONS: Responding to stress by using social support is linked to lower cortisol responses to social stress and diurnal cortisol activity for women with implicit avoidance of social threat cues. PMID- 27189782 TI - The sound of emotions-Towards a unifying neural network perspective of affective sound processing. AB - Affective sounds are an integral part of the natural and social environment that shape and influence behavior across a multitude of species. In human primates, these affective sounds span a repertoire of environmental and human sounds when we vocalize or produce music. In terms of neural processing, cortical and subcortical brain areas constitute a distributed network that supports our listening experience to these affective sounds. Taking an exhaustive cross-domain view, we accordingly suggest a common neural network that facilitates the decoding of the emotional meaning from a wide source of sounds rather than a traditional view that postulates distinct neural systems for specific affective sound types. This new integrative neural network view unifies the decoding of affective valence in sounds, and ascribes differential as well as complementary functional roles to specific nodes within a common neural network. It also highlights the importance of an extended brain network beyond the central limbic and auditory brain systems engaged in the processing of affective sounds. PMID- 27189783 TI - Revealing the quality of movement: A meta-analysis review to quantify the thresholds to pathological variability during standing and walking. AB - Neuromotor processes are inherently noisy, which results in variability during movement and fluctuations in motor control. Although controversial, low levels of variability are traditionally considered healthy, while increased levels are thought to be pathological. This systematic review and meta-analysis of the literature investigates the thresholds between healthy and pathological task variability. After examining 13,195 publications, 109 studies were included. Results from over 3000 healthy subjects and 2775 patients revealed an overall positive effect size of pathology on variability of 0.59 for walking and 0.80 for sway. For the coefficient of variation of stride time (ST) and sway area (SA), upper thresholds of 2.6% and 265mm(2) discriminated pathological from asymptomatic performance, while 1.1% and 62mm(2) identified the lower thresholds for pathological variability. This window of healthy performance now provides science based evidence for the discrimination of both extremely low and extremely high levels of variability in the identification as well as standardised monitoring of functional status in neurological cases. PMID- 27189780 TI - Multiple pathway assessment to predict anti-atherogenic efficacy of drugs targeting macrophages in atherosclerotic plaques. AB - BACKGROUND: Macrophages play a central role in atherosclerosis development and progression, hence, targeting macrophage activity is considered an attractive therapeutic. Recently, we documented nanomedicinal delivery of the anti inflammatory compound prednisolone to atherosclerotic plaque macrophages in patients, which did however not translate into therapeutic efficacy. This unanticipated finding calls for in-depth screening of drugs intended for targeting plaque macrophages. METHODS AND RESULTS: We evaluated the effect of several candidate drugs on macrophage activity, rating overall performance with respect to changes in cytokine release, oxidative stress, lipid handling, endoplasmic reticulum (ER) stress, and proliferation of macrophages. Using this in vitro approach, we observed that the anti-inflammatory effect of prednisolone was counterbalanced by multiple adverse effects on other key pathways. Conversely, pterostilbene, T0901317 and simvastatin had an overall anti atherogenic effect on multiple pathways, suggesting their potential for liposomal delivery. CONCLUSION: This dedicated assay setup provides a framework for high throughput assessment. Further in vivo studies are warranted to determine the predictive value of this macrophage-based screening approach and its potential value in nanomedicinal drug development for cardiovascular patients. PMID- 27189784 TI - A touch with words: Dynamic synergies between manual actions and language. AB - Manual actions are a hallmark of humanness. Their underlying neural circuitry gives rise to species-specific skills and interacts with language processes. In particular, multiple studies show that hand-related expressions - verbal units evoking manual activity - variously affect concurrent manual actions, yielding apparently controversial results (interference, facilitation, or null effects) in varied time windows. Through a systematic review of 108 experiments, we show that such effects are driven by several factors, such as the level of verbal processing, action complexity, and the time-lag between linguistic and motor processes. We reconcile key empirical patterns by introducing the Hand-Action Network Dynamic Language Embodiment (HANDLE) model, an integrative framework based on neural coupling dynamics and predictive-coding principles. To conclude, we assess HANDLE against the backdrop of other action-cognition theories, illustrate its potential applications to understand high-level deficits in motor disorders, and discuss key challenges for further development. In sum, our work aligns with the 'pragmatic turn', moving away from passive and static representationalist perspectives to a more dynamic, enactive, and embodied conceptualization of cognitive processes. PMID- 27189785 TI - Tris (dibenzylideneacetone) dipalladium: a small-molecule palladium complex is effective in inducing apoptosis in chronic lymphocytic leukemia B-cells. AB - Here we tested impact of Tris (dibenzylideneacetone) dipalladium (Tris-DBA) on chronic lymphocytic leukemia (CLL) B-cell survival. Indeed, treatment of CLL B cells with Tris-DBA induced apoptosis in a dose-dependent manner irrespective of IgVH mutational status. Further analyses suggest that Tris-DBA-induced apoptosis involves reduced expression of the anti-apoptotic proteins Bcl-xL, and XIAP with an upregulation of the pro-apoptotic protein BIM in CLL B-cells. Our findings also indicate that Tris-DBA targets the ribosomal protein (rp)-S6, an essential component of the Akt/mTOR signaling axis in CLL B-cells. Of interest, CLL bone marrow stromal cells were unable to protect the leukemic B cells from Tris-DBA induced apoptosis in an in vitro co-culture system. Finally, co-administration of Tris-DBA and the purine nucleoside analog fludarabine (F-ara-A) augmented CLL B cell apoptosis levels in vitro showing synergistic effects. In total, Tris-DBA is effective at inducing apoptosis in CLL B-cells even in the presence of stromal cells likely by targeting directly the signal mediator, rpS6. PMID- 27189788 TI - Theories, timing and choice of audience: some key tensions in health psychology and a response to commentaries on Ogden (2016). PMID- 27189786 TI - Multicolor 4D Fluorescence Microscopy using Ultrathin Bessel Light Sheets. AB - We demonstrate a simple and efficient method for producing ultrathin Bessel ('non diffracting') light sheets of any color using a line-shaped beam and an annulus filter. With this robust and cost-effective technology, we obtained two-color, 3D images of biological samples with lateral/axial resolution of 250 nm/400 nm, and high-speed, 4D volume imaging of 20 MUm sized live sample at 1 Hz temporal resolution. PMID- 27189787 TI - Diversity in plant hydraulic traits explains seasonal and inter-annual variations of vegetation dynamics in seasonally dry tropical forests. AB - We assessed whether diversity in plant hydraulic traits can explain the observed diversity in plant responses to water stress in seasonally dry tropical forests (SDTFs). The Ecosystem Demography model 2 (ED2) was updated with a trait-driven mechanistic plant hydraulic module, as well as novel drought-phenology and plant water stress schemes. Four plant functional types were parameterized on the basis of meta-analysis of plant hydraulic traits. Simulations from both the original and the updated ED2 were evaluated against 5 yr of field data from a Costa Rican SDTF site and remote-sensing data over Central America. The updated model generated realistic plant hydraulic dynamics, such as leaf water potential and stem sap flow. Compared with the original ED2, predictions from our novel trait driven model matched better with observed growth, phenology and their variations among functional groups. Most notably, the original ED2 produced unrealistically small leaf area index (LAI) and underestimated cumulative leaf litter. Both of these biases were corrected by the updated model. The updated model was also better able to simulate spatial patterns of LAI dynamics in Central America. Plant hydraulic traits are intercorrelated in SDTFs. Mechanistic incorporation of plant hydraulic traits is necessary for the simulation of spatiotemporal patterns of vegetation dynamics in SDTFs in vegetation models. PMID- 27189791 TI - Korean red ginseng extract enhances paclitaxel distribution to mammary tumors and its oral bioavailability by P-glycoprotein inhibition. AB - 1. Drug efflux by P-glycoprotein (P-gp) is a common resistance mechanism of breast cancer cells to paclitaxel, the primary chemotherapy in breast cancer. As a means of overcoming the drug resistance-mediated failure of paclitaxel chemotherapy, the potential of Korean red ginseng extract (KRG) as an adjuvant chemotherapy has been reported only in in vitro. Therefore, we assessed whether KRG alters P-gp mediated paclitaxel efflux, and therefore paclitaxel efficacy in in vitro and vivo models. 2. KRG inhibited P-gp protein expression and transcellular efflux of paclitaxel in MDCK-mdr1 cells, but KRG was not a substrate of P-gp ATPase. In female rats with mammary tumor, the combination of paclitaxel with KRG showed the greater reduction of tumor volumes, lower P-gp protein expression and higher paclitaxel distribution in tumors, and greater oral bioavailability of paclitaxel than paclitaxel alone. 3. From these results, KRG increased systemic circulation of oral paclitaxel and its distribution to tumors via P-gp inhibition in rats and under the current study conditions. PMID- 27189792 TI - Malignant cerebral swelling following cranioplasty. AB - Over the past few years there have been a number of case reports and small cohort studies that have described so called "malignant" cerebral swelling following an uneventful cranioplasty procedure. The pathophysiology remains to be established however it has been suggested that it may be related to a combination of failure of autoregulation and the use of closed vacuum suction drainage. The current study presents three further patients who had had a decompressive hemicraniectomy for ischaemic stroke. If decompressive craniectomy is utilised in the management of neurological emergencies, close attention and wider reporting of this type of complication is required not only to focus attention on possible management strategies, but also to determine which patients are at most risk of this devastating complication. PMID- 27189793 TI - Comparison of self-determination of students with disabilities: multivariate and discriminant function analyses. AB - BACKGROUND: Self-determined behaviour is composed of multiple, interrelated component elements, and yet little empirical study has researched the self determination components other than choice making and goal setting. Also, few theoretical relationships have been drawn between the component elements of self determined behaviour and the impact of disability category. Therefore, this study examined profiles of the combination of three self-report measures of component elements of self-determined behaviour (autonomous functioning, problem solving and internal locus of control) between two groups (ID and learning disabilities/emotional disorders). METHOD: We analysed data from 96 middle school and high school students ages 13 through 22 years who completed three self-report instruments of the Autonomy - section 1 of The Arc's Self-determination Scale, the Problem Solving Survey and the Nowicki-Strickland Locus of Control Scale. A multivariate analysis of covariance was conducted to investigate the differences between the two groups after controlling for the developmental effects of age. A discriminant function analysis examined whether membership of the two groups could be predicted from the three component elements. RESULTS: Results showed that each group had different profiles within the combined three component elements of self-determination but groups were not different on any single measure of component elements of self-determined behaviour exclusively. The combination of three variables was useful in confirming the membership of two dichotomous groups. CONCLUSIONS: Score differences on the three component behaviour imply that the two groups have different instructional needs and therefore require differentiated instructional approaches. The three measures of the component elements of self-determined behaviour collectively separate the two groups, suggesting that the component elements should be considered in a combination as opposed to being treated as individual elements in the context of discussing self-determined behaviour. PMID- 27189794 TI - Enhanced Performance by Enlarged Nano-pores of Holly Leaf-derived Lamellar Carbon for Sodium-ion Battery Anode. AB - Lamellar hard carbon derived from holly leaf with enlarged pores of tiny graphite like domains and meso-pores was prepared by hydrothermal followed high temperature pyrolysis process. Benefiting from the enlarged nano-pores of tiny graphite-like domains and the thin sheet structure with meso-pores, the derived carbon delivered a high reversible capacity of 318 mAh g(-1) at a current rate of 20 mA g(-1) and excellent rate capability as the anode of sodium-ion battery. And the hydrothermal followed high temperature pyrolysis method was also confirmed an effective approach for betula platyphylla and sophora japonica leaf as precursor respectively to synthesis hard carbon of lamellar structure with enlarged nano pores of tiny graphite-like domains. PMID- 27189795 TI - Relational Patterns and the Development of the Alliance: A Systematic Comparison of two Cases. AB - : A systematic case study approach was taken to explore the impact of client and therapist relational patterns on the development of the therapeutic alliance and symptom reduction in two cases of psychodynamic psychotherapy treated by the same therapist. The cases were selected from a larger sample and represent two distinct trajectories of alliance development: improvement versus deterioration. The comparison was based on participants' ongoing narratives about each other and about significant others, using the Relationship Anecdote Paradigm (RAP) interview. The qualitative findings were triangulated with process and outcome measures assessed at four time points during the year of treatment. We hypothesized that different therapeutic processes, including different handling by the therapist of interpersonal difficulties as they arose in treatment, could explain the two distinct trajectories of alliance development and symptom change within the caseload of one therapist. Results indicate two linked elements that may explain a steady increase in alliance and decrease in symptoms in one case, compared with the second case that started with an increase in alliance and symptom improvement, but gradually reached an impasse and a setback in symptoms. One element was the extent to which client's and therapist's relational patterns clashed, impacting each other negatively. The second was the extent to which differences and disagreements were stated openly and negotiated so that the therapist could flexibly adapt to meet the client's relational patterns in one case versus inability to do so in the other. Implications for training and other psychotherapy orientations are discussed. Copyright (c) 2016 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: The interaction of client and therapist relational patterns may be a key factor in the development of the therapeutic alliance and might potentially impact client outcome. Therapeutic practice will likely be improved if therapists are more aware of their own relational patterns and the ways these interact with their clients' relational patterns. Striving for this awareness should probably be a main focal point for therapists throughout their careers, in their training, supervisions and personal therapies. PMID- 27189796 TI - A reappraisal of clinical research on arterial stiffness in hypertension in France. PMID- 27189797 TI - Baroreflex activation therapy: future use as therapy for severe or resistant hypertension? PMID- 27189798 TI - Cystic fibrosis. AB - Cystic fibrosis is an autosomal recessive, monogenetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The gene defect was first described 25 years ago and much progress has been made since then in our understanding of how CFTR mutations cause disease and how this can be addressed therapeutically. CFTR is a transmembrane protein that transports ions across the surface of epithelial cells. CFTR dysfunction affects many organs; however, lung disease is responsible for the vast majority of morbidity and mortality in patients with cystic fibrosis. Prenatal diagnostics, newborn screening and new treatment algorithms are changing the incidence and the prevalence of the disease. Until recently, the standard of care in cystic fibrosis treatment focused on preventing and treating complications of the disease; now, novel treatment strategies directly targeting the ion channel abnormality are becoming available and it will be important to evaluate how these treatments affect disease progression and the quality of life of patients. In this Primer, we summarize the current knowledge, and provide an outlook on how cystic fibrosis clinical care and research will be affected by new knowledge and therapeutic options in the near future. For an illustrated summary of this Primer, visit: http://go.nature.com/4VrefN. PMID- 27189799 TI - Efficient plasma-enhanced method for layered LiNi1/3Co1/3Mn1/3O2 cathodes with sulfur atom-scale modification for superior-performance Li-ion batteries. AB - In order to improve the electrochemical performance of LiNi1/3Co1/3Mn1/3O2 as a lithium insertion positive electrode material, atom-scale modification was realized to obtain the layered oxysulfide LiNi1/3Co1/3Mn1/3O2-xSx using a novel plasma-enhanced doping strategy. The structure and electrochemical performance of LiNi1/3Co1/3Mn1/3O2-xSx are investigated systematically, which confirms that the S doping can make the structure stable and benefit the electrochemical performance. The phys-chemical characterizations indicate that oxygen atoms in the initial LiNi1/3Co1/3Mn1/3O2 have been partially replaced by S atoms. It should be pointed out that the atom-scale modification does not significantly alter the intrinsic structure of the cathode. Compared to the pristine material, the LiNi1/3Co1/3Mn1/3O2-xSx shows a superior performance with a higher capacity (200.4 mA h g(-1)) and a significantly improved cycling stability (maintaining 94.46% of its initial discharge capacity after 100 cycles). Moreover, it has an excellent rate performance especially at elevated performance, which is probably due to the faster Li(+) transportation after S doping into the layered structure. All the results show that the atom-scale modification with sulfur atoms on LiNi1/3Co1/3Mn1/3O2, which significantly improved the electrochemical performance, offers a novel anionic doping strategy to realize the atom-scale modification of electrode materials to improve their electrochemical performance. PMID- 27189800 TI - Matching relations for optimal entanglement concentration and purification. AB - The bilateral controlled NOT (CNOT) operation plays a key role in standard entanglement purification process, but the CNOT operation may not be the optimal joint operation in the sense that the output entanglement is maximized. In this paper, the CNOT operations in both the Schmidt-projection based entanglement concentration and the entanglement purification schemes are replaced with a general joint unitary operation, and the optimal matching relations between the entangling power of the joint unitary operation and the non-maximal entangled channel are found for optimizing the entanglement in- crement or the output entanglement. The result is somewhat counter-intuitive for entanglement concentration. The output entanglement is maximized when the entangling power of the joint unitary operation and the quantum channel satisfy certain relation. There exist a variety of joint operations with non-maximal entangling power that can induce a maximal output entanglement, which will greatly broaden the set of the potential joint operations in entanglement concentration. In addition, the entanglement increment in purification process is maximized only by the joint unitary operations (including CNOT) with maximal entangling power. PMID- 27189801 TI - 2015 Nepal Earthquake: Analysis of Child Rescue and Treatment by a Field Hospital. AB - OBJECTIVE: To retrospectively analyze the rescue and treatment of pediatric patients by the Chinese Red Cross medical team during the Nepal earthquake relief. METHODS: The medical team set up a field hospital; the pediatric clinic consisted of 1 pediatrician and several nurses. Children younger than 18 years old were placed in the pediatric clinic for injury examination and treatment. RESULTS: During the 7-day period of medical assistance (the second to third week after the earthquake), a total of 108 pediatric patients were diagnosed and treated, accounting for 2.8% of the total patients. The earthquake-related injuries mainly required surgical dressing and debridement. No severe limb fractures or traumatic brain injuries were found. Infection of the respiratory tract, the gastrointestinal tract, and the skin were the most common ailments, accounting for 42.3%, 18.5%, and 16.7%, respectively, of the total treated patients. CONCLUSION: Two to 3 weeks after the earthquake, the admitted pediatric patients mainly displayed respiratory and gastrointestinal infections. When developing a rescue plan and arranging medical resources, we should consider the necessity of treating non-disaster-related conditions. (Disaster Med Public Health Preparedness. 2016;page 1 of 4). PMID- 27189802 TI - Can Preconsent Eliminate Some Barriers to Clinical Trial Enrollment of Children With Sickle Cell Disease in Crisis? PMID- 27189803 TI - Dietary and pharmacological intervention to mitigate the cardiopulmonary effects of air pollution toxicity. AB - BACKGROUND: Exposure to air pollution contributes importantly to excess morbidity and mortality. And while regulatory actions under the "Clean Air Act" have saved millions of lives by improving air quality, there are still millions of people in the U.S. who live in areas where particulate air pollution (PM) levels exceed the U.S. Environmental Protection Agency's National Ambient Air Quality Standards. Therefore, apart from such localities working to attain such standards the protection of the health of public and in particular those at high risk might benefit from interventional strategies that would ameliorate air pollution's adverse health effects. Because inflammation and oxidative stress appear to mediate the health effects of air pollution, one interventional approach to consider is the use of dietary supplementation or medication with anti inflammatory or antioxidant properties to block the biological responses that initiate the pathophysiological process that culminates in adverse health effects. SCOPE OF REVIEW: This article reviews the capability of dietary supplementation, such as antioxidant vitamins, polyunsaturated fatty acids, and medications as a strategy to mitigate air pollution-induced subclinical cardiopulmonary effects. MAJOR CONCLUSIONS: Antioxidant vitamins C and E protect the lungs against short-term ozone and PM exposure. Polyunsaturated fatty acids, such as fish oil and olive oil appear to offer protection against short-term air pollution-induced adverse cardiovascular responses. GENERAL SIGNIFICANCE: Taking dietary supplements or medications with antioxidant or anti-inflammatory properties has the potential to provide at least partial protection against air pollution-induced adverse health effects in those individuals who are known to be most susceptible, namely those with pre-existing respiratory and cardiovascular diseases. This article is part of a Special Issue entitled Air Pollution, edited by Wenjun Ding, Andrew J. Ghio and Weidong Wu. PMID- 27189804 TI - A case of mistaken identity: CD11c-eYFP(+) cells in the normal mouse brain parenchyma and neural retina display the phenotype of microglia, not dendritic cells. AB - Under steady-state conditions the central nervous system (CNS) is traditionally thought to be devoid of antigen presenting cells; however, putative dendritic cells (DCs) expressing enhanced yellow fluorescent protein (eYFP) are present in the retina and brain parenchyma of CD11c-eYFP mice. We previously showed that these mice carry the Crb1(rd8) mutation, which causes retinal dystrophic lesions; therefore we hypothesized that the presence of CD11c-eYFP(+) cells within the CNS may be due to pathology associated with the Crb1(rd8) mutation. We generated CD11c-eYFP Crb1(wt/wt) mice and compared the distribution and immunophenotype of CD11c-eYFP(+) cells in CD11c-eYFP mice with and without the Crb1(rd8) mutation. The number and distribution of CD11c-eYFP(+) cells in the CNS was similar between CD11c-eYFP Crb1(wt/wt) and CD11c-eYFP Crb1(rd8/rd8) mice. CD11c-eYFP(+) cells were distributed throughout the inner retina, and clustered in brain regions that receive input from the external environment or lack a blood-brain barrier. CD11c eYFP(+) cells within the retina and cerebral cortex of CD11c-eYFP Crb1(wt/wt) mice expressed CD11b, F4/80, CD115 and Iba-1, but not DC or antigen presentation markers, whereas CD11c-eYFP(+) cells within the choroid plexus and pia mater expressed CD11c, I-A/I-E, CD80, CD86, CD103, DEC205, CD8alpha and CD135. The immunophenotype of CD11c-eYFP(+) cells and microglia within the CNS was similar between CD11c-eYFP Crb1(wt/wt) and CD11c-eYFP Crb1(rd8/rd8) mice; however, CD11c and I-A/I-E expression was significantly increased in CD11c-eYFP Crb1(rd8/rd8) mice. This study demonstrates that the overwhelming majority of CNS CD11c-eYFP(+) cells do not display the phenotype of DCs or their precursors and are most likely a subpopulation of microglia. GLIA 2016. GLIA 2016;64:1331-1349. PMID- 27189806 TI - Post-traumatic growth following a first episode of psychosis: a scoping review. AB - AIM: A first-episode psychosis (FEP) is a traumatic experience that can often result in great suffering. However, in addition to suffering, persons affected by FEP may also experience post-traumatic growth (PTG) or the perception that good has followed psychosis. Although much is known concerning the negative outcomes following FEP, little attention has been given to the state of scientific knowledge on PTG following FEP. The aim of this study is to determine the state of knowledge concerning PTG following FEP to help set the stage for a full systematic review. METHODS: A scoping review was conducted following six steps: identifying the research question and relevant studies, selecting studies, charting the data, coding and summarizing results and consulting with relevant stakeholders regarding the findings. RESULTS: Post-traumatic growth following FEP was described mostly as following the process of recovery and primarily, in qualitative articles. Themes related to PTG included developing positive character traits, making positive lifestyle changes, developing stronger connections with others, integrating the FEP with the self, experiencing greater religiosity and appreciating life more. CONCLUSIONS: In addition to the negative aftermath of FEP, PTG may also occur. Evidence of PTG following FEP will be examined in a systematic review focused on the recovery and qualitative literature. PMID- 27189807 TI - Mussel-Inspired Antibacterial and Biocompatible Silver-Carbon Nanotube Composites: Green and Universal Nanointerfacial Functionalization. AB - Nanointerfacial decoration of silver nanoparticles (AgNPs) is an ideal protocol to improve the antibacterial efficiency of diverse nanomaterials, including carbon nanotube (CNT), graphene, and many other intensively studied nanoarchitectures, which provides a tremendous possibility for designing advanced antibacterial biomaterials and biomedical devices. However, the direct exposure of AgNPs will lead to potential mammalian cell apoptosis and death, which significantly limits their biological applications. In this study, we demonstrated a green and one-step approach to achieve robust antibacterial and highly biocompatible AgNP-CNT composites. AgNPs were produced via mussel-inspired "one-step" in situ reduction and coating process and were anchored onto the surface of a CNT. Simultaneously, protective polymer layers were formed to shield the AgNPs to improve their biocompatibility. Because of the bactericidal efficiency of AgNPs, the composites showed robust antibacterial efficiency in terms of both inhibition of bacterial cell growth and bacterial killing activity. Moreover, owing to the shielding effects of the polymer coatings, the nanocomposites exhibited much improved compatibility with human umbilical vein endothelial cells compared with bare AgNP-CNTs. Furthermore, the nanocomposites exhibited good stability in psychological solutions. With integrated excellent antibacterial activity, cell compatibility, and long-term stability, it is believed that the synthesized AgNP-CNT composites will be of promising potential in antibacterial applications. Meanwhile, the proposed strategies can also be applied to fabricate many other kinds of AgNP-based composites because of the versatile functionality of catecholic polymers. PMID- 27189805 TI - VEGF-B inhibits hyperglycemia- and Macugen-induced retinal apoptosis. AB - Vascular endothelial growth factor B (VEGF-B) was discovered a long time ago. However, its role in hyperglycemia- and VEGF-A inhibition-induced retinal apoptosis remains unknown thus far. Yet, drugs that can block VEGF-B are being used to treat patients with diabetic retinopathy and other ocular neovascular diseases. It is therefore urgent to have a better understanding of the function of VEGF-B in these pathologies. Here, we report that both streptozotocin (STZ) induced diabetes in rats and Macugen intravitreal injection in mice leads to retinal apoptosis in retinal ganglion cell and outer nuclear layers respectively. Importantly, VEGF-B treatment by intravitreal injection markedly reduced retinal apoptosis in both models. We further reveal that VEGF-B and its receptors, vascular endothelial growth factor 1 (VEGFR1) and neuropilin 1 (NP1), are abundantly expressed in rat retinae and choroids and are upregulated by high glucose with concomitant activation of Akt and Erk. These data highlight an important function of VEGF-B in protecting retinal cells from apoptosis induced by hyperglycemia and VEGF-A inhibition. VEGF-B may therefore have a therapeutic potential in treating various retinal degenerative diseases, and modulation of VEGF-B activity in the eye needs careful consideration. PMID- 27189809 TI - Does the diameter of abdominal aortic aneurysm influence late survival following abdominal aortic aneurysm repair? A systematic review and meta-analysis. AB - BACKGROUND: Studies reporting the influence of preoperative abdominal aortic aneurysm diameter on late survival following abdominal aortic aneurysm repair have not been consistent. AIM: To report the influence of abdominal aortic aneurysm diameter on overall long-term survival following abdominal aortic aneurysm repair. METHODS: Embase, Medline and the Cochrane electronic databases were searched to identify articles reporting the influence of abdominal aortic aneurysm diameter on late survival following open aneurysm repair and endovascular aneurysm repair published up to April 2015. Data were extracted from multivariate analysis; estimated risks were expressed as hazard ratio. RESULTS: A total of 2167 titles/abstracts were retrieved, of which 76 studies were fully assessed; 19 studies reporting on 22,104 patients were included. Preoperative larger abdominal aortic aneurysm size was associated with a worse survival compared to smaller aneurysms with a pooled hazard ratio of 1.14 (95% CI: 1.09 1.18), per 1 cm increase in abdominal aortic aneurysm diameter. Subgroup analysis of the different types of repair was performed and the hazard ratio (95% CI), for open aneurysm repair and endovascular aneurysm repair were 1.08 (1.03-1.12) and 1.20 (1.15-1.25), respectively, per 1 cm increase. There was a significant difference between the groups p < 0.02. CONCLUSIONS: This meta-analysis suggests that preoperative large abdominal aortic aneurysm independently influences overall late survival following abdominal aortic aneurysm repair, and this association was greater in abdominal aortic aneurysm repaired with endovascular aneurysm repair. PMID- 27189810 TI - Multistate empirical valence bond study of temperature and confinement effects on proton transfer in water inside hydrophobic nanochannels. AB - Microscopic characteristics of an aqueous excess proton in a wide range of thermodynamic states, from low density amorphous ices (down to 100 K) to high temperature liquids under the critical point (up to 600 K), placed inside hydrophobic graphene slabs at the nanometric scale (with interplate distances between 3.1 and 0.7 nm wide) have been analyzed by means of molecular dynamics simulations. Water-proton and carbon-proton forces were modeled with a multistate empirical valence bond method. Densities between 0.07 and 0.02 A(-3) have been considered. As a general trend, we observed a competition between effects of confinement and temperature on structure and dynamical properties of the lone proton. Confinement has strong influence on the local structure of the proton, whereas the main effect of temperature on proton properties is observed on its dynamics, with significant variation of proton transfer rates, proton diffusion coefficients, and characteristic frequencies of vibrational motions. Proton transfer is an activated process with energy barriers between 1 and 10 kJ/mol for both proton transfer and diffusion, depending of the temperature range considered and also on the interplate distance. Arrhenius-like behavior of the transfer rates and of proton diffusion are clearly observed for states above 100 K. Spectral densities of proton species indicated that in all states Zundel-like and Eigen-like complexes survive at some extent. (c) 2016 Wiley Periodicals, Inc. PMID- 27189808 TI - ApoE4 expression accelerates hippocampus-dependent cognitive deficits by enhancing Abeta impairment of insulin signaling in an Alzheimer's disease mouse model. AB - The apolipoprotein E4 (ApoE4) is the strongest genetic risk factor for Alzheimer's disease (AD). The AD brain was shown to be insulin resistant at end stage, but the interplay between insulin signaling, ApoE4 and Abeta across time, and their involvement in memory decline is unclear. To investigate insulin response in the ageing mouse hippocampus, we crossed the human ApoE-targeted replacement mice with the mutant human amyloid precursor protein (APP) mice (ApoExAPP). While hippocampal Abeta levels were comparable between ApoE3xAPP and ApoE4xAPP mice at 26 weeks, insulin response was impaired in the ApoE4xAPP hippocampus. Insulin treatment was only able to stimulate insulin signaling and increased AMPA-GluR1 phosphorylation in forskolin pre-treated hippocampal slices from ApoE3xAPP mice. In ApoE4xAPP mice, insulin dysfunction was also associated with poorer spatial memory performance. Using dissociated hippocampal neuron in vitro, we showed that insulin response in ApoE3 and ApoE4 neurons increased AMPA receptor-mediated miniature excitatory postsynaptic current (mEPSC) amplitudes and GluR1-subunit insertion. Pre-treatment of ApoE3 neurons with Abeta42 did not affect insulin-mediated GluR1 subunit insertion. However, impaired insulin sensitivity observed only in the presence of ApoE4 and Abeta42, attenuated GluR1 subunit insertion. Taken together, our results suggest that ApoE4 enhances Abeta inhibition of insulin-stimulated AMPA receptor function, which accelerates memory impairment in ApoE4xAPP mice. PMID- 27189811 TI - Rhodium(I)-Catalyzed Benzannulation of Heteroaryl Propargylic Esters: Synthesis of Indoles and Related Heterocycles. AB - A de novo synthesis of a benzene ring allows for the preparation of a diverse range of heterocycles including indoles, benzofurans, benzothiophenes, carbazoles, and dibenzofurans from simple heteroaryl propargylic esters using a unified carbonylative benzannulation strategy. Multiple substituents can be easily introduced to the C4-C7 positions of indoles and related heterocycles. PMID- 27189812 TI - Biologic Variability of Soluble ST2 in Patients With Stable Chronic Heart Failure and Implications for Monitoring. AB - Soluble ST2 (sST2) is a novel biomarker implicated in myocardial remodeling and fibrosis. Recent studies in normal subjects have suggested that the biologic variability (BV) of sST2 is significantly lower than that of the B-type natriuretic peptides and N-terminal pro B-type natriuretic peptide (NTproBNP). It may, consequently, be a better biomarker for monitoring patients with chronic heart failure (CHF). To date, no published studies have examined the BV of sST2 in a heart failure population. Blood samples from 50 outpatients with pharmacologically optimized stable CHF and persistent left ventricular dysfunction (ejection fraction <40%) were collected at baseline, 1 hour, 1 month, 3 months, and 6 months. Using log-transformed data, mean intra-individual coefficients of variation (CVI) and subsequent reference change values were calculated for both NTproBNP and sST2. Results demonstrate significantly lower CVI and reference change values for sST2 compared with NTproBNP at 1 month (12.02 [36%] vs 36.75 [103%]), p <0.001, 3 months (12.23 [36%] vs 40.98 [114%]), p <0.001, and 6 months (16.41 [47%] vs 46.02 [128%]), p <0.001. In conclusion, the BV of sST2 is significantly lower than that of NTproBNP in patients with CHF. These results support previous indications that sST2 may be a better biomarker for monitoring such patients. PMID- 27189813 TI - Abundance and Significance of Iron, Zinc, Copper, and Calcium in the Hearts of Patients With Friedreich Ataxia. AB - Cardiomyopathy is a frequent cause of death in patients with Friedreich ataxia (FA), and a characteristic pathological feature is the focal accumulation of iron (Fe) in cardiomyocytes. This restricted localization of the metal contrasts with the diffuse cardiac Fe overload in hemochromatosis and transfusion siderosis. Nevertheless, heart Fe in FA contributes to cardiomyocyte necrosis, inflammation, and scarring as the disease progresses. A putative mechanism of cardiomyopathy in FA is Fe-mediated oxidative damage. Two other transition metals zinc (Zn) and copper (Cu), are diffusely distributed throughout normal hearts and the hearts of patients with FA. The myocardium in FA is also prone to deposits of calcium in the form of scattered concretions. In this study, heart tissues (left and right ventricular walls and ventricular septum) of 23 patients with genetically confirmed FA and 8 normal controls were obtained at autopsy and analyzed for Fe, Zn, Cu, and calcium. The principal assay methods were inductively coupled plasma optical emission spectrometry and plasma mass spectrometry. Total levels of Fe in bulk extracts were not significantly higher than normal, and the concentrations of Zn also remained in the normal range. Cu levels, however, were significantly lower in FA. In conclusion, the decrease of Cu may be important in consideration of the potential benefit of Cu supplements in FA cardiomyopathy. PMID- 27189815 TI - Prediction of Appropriate Shocks Using 24-Hour Holter Variables and T-Wave Alternans After First Implantable Cardioverter-Defibrillator Implantation in Patients With Ischemic or Nonischemic Cardiomyopathy. AB - In patients treated with implantable cardioverter defibrillator (ICD), prediction of both overall survival and occurrence of shocks is important if improved patient selection is desired. We prospectively studied the predictive value of biomarkers and indexes of cardiac and renal function and spectral microvolt T wave alternans testing and 24-hour Holter variables in a population who underwent first ICD implantation. Consecutive patients in sinus rhythm with ischemic or dilated cardiomyopathy scheduled for primary or secondary prophylactic ICD implantation were enrolled. Exercise microvolt T-wave alternans and 24-hour Holter for number of ventricular premature contractions (VPCs), deceleration capacity, heart rate variability, and heart rate turbulence were done. Death of any cause and first appropriate ICD shock were defined as end points. Over 33 +/- 15 months of follow-up, 36 of 253 patients (14%) received appropriate shocks and 39 of 253 patients (15%) died. Only 3 of 253 patients (1%) died after receiving at least 1 appropriate shock. In univariate analyses, New York Heart Association class, ejection fraction, N-terminal pro brain-type natriuretic peptide (NT proBNP), renal function, ICD indication, deceleration capacity, heart rate variability, and heart rate turbulence were predictive of all-cause mortality and VPC number and deceleration capacity predicted first appropriate shock. NT-proBNP (>=1,600 pg/ml) was identified as the only independent predictor of all-cause mortality (hazard ratio 3.0, confidence interval 1.3 to 7.3, p = 0.014). In contrast, VPC number predicted appropriate shocks (hazard ratio 2.3, confidence interval 1.0 to 5.5, p = 0.047) as the only independent risk marker. In conclusion, NT-proBNP is a strong independent predictor of mortality in a typical prospective cohort of newly implanted patients with ICD, among many electrocardiographic and clinical variables studied. Number of VPCs was identified as a predictor of appropriate shocks (clinicaltrials.gov: NCT02010515). PMID- 27189814 TI - Effect of Hepatitis C Positivity on Survival in Adult Patients Undergoing Heart Transplantation (from the United Network for Organ Sharing Database). AB - Concerns exist regarding orthotropic heart transplantation in hepatitis C virus (HCV) seropositive recipients. Thus, a national registry was accessed to evaluate early and late outcome in HCV seropositive recipients undergoing heart transplant. Retrospective analysis of the United Network for Organ Sharing registry (1991 to 2014) was performed to evaluate recipient profile and clinical outcome of patients with HCV seropositive (HCV +ve) and seronegative (HCV -ve). Adjusted results of early mortality and late survival were compared between cohorts. From 23,507 patients (mean age 52 years; 75% men), 481 (2%) were HCV +ve (mean age 52 years; 77% men). Annual proportion of HCV +ve recipients was comparable over the study period (range 1.3% to 2.7%; p = 0.2). The HCV +ve cohort had more African-American (22% vs 17%; p = 0.01), previous left ventricular assist device utilization (21% vs 14%; p <0.01) and more hepatitis B core Ag+ve recipients (17% vs 5%; p <0.01). However, both cohorts were comparable in terms of extracorporeal membrane oxygenator usage (p = 0.7), inotropic support (p = 0.2), intraaortic balloon pump (p = 0.7) support, serum creatinine (p = 0.7), and serum bilirubin (p = 0.7). Proportion of status 1A patients was similar (24% HCV + vs 21% HCV -); however, wait time for HCV +ve recipients were longer (mean 23 vs 19 days; p <0.01). Among donor variables, age (p = 0.8), hepatitis B status (p = 0.4), and Center for Diseases Control high-risk status (p = 0.9) were comparable in both cohorts. At a median follow-up of 4 years, 67% patients were alive, 28% died, and 1.1% were retransplanted (3.4% missing). Overall survival was worse in the HCV+ cohort (64.3% vs 72.9% and 43.2% vs 55% at 5 and 10 years; p <0.01), respectively. Late renal (odds ratio [OR] 1.2 [1 to 1.6]; p = 0.02) and liver dysfunction (odds ratio 4.5 [1.2 to 15.7]; p = 0.01) occurs more frequently in HCV +ve recipients. On adjusted analysis, HCV seropositivity is associated with poorer survival (hazard ratio for mortality 1.4 [1.1 to 1.6]; p <0.001). In conclusion, a small proportion of patients receiving a heart transplant in the United States have hepatitis C. Despite comparable preoperative hepatic function, hepatitis C seropositive recipients demonstrate poorer long-term survival. PMID- 27189816 TI - Validation of the 2014 European Society of Cardiology Sudden Cardiac Death Risk Prediction Model in Hypertrophic Cardiomyopathy in a Reference Center in South America. AB - Sudden cardiac death (SCD) is a common cause of death in hypertrophic cardiomyopathy (HC). Our aim was to conduct an external and independent validation in South America of the 2014 European Society of Cardiology (ESC) SCD risk prediction model to identify patients requiring an implantable cardioverter defibrillator. This study included 502 consecutive patients with HC followed from March, 1993 to December, 2014. A combined end point of SCD or appropriate implantable cardioverter defibrillator therapy was assessed. For the quantitative estimation of individual 5-year SCD risk, we used the formula: 1 - 0.998(exp(Prognostic index)). Our database also included the abnormal blood pressure response to exercise as a risk marker. We analyzed the 3 categories of 5 year risk proposed by the ESC: low risk (LR) <4%; intermediate risk (IR) >=4% to <6%, and high risk (HR) >=6%. The LR group included 387 patients (77%); the IR group 39 (8%); and the HR group 76 (15%). Fourteen patients (3%) had SCD/appropriate implantable cardioverter defibrillator therapy (LR: 0%; IR: 2 of 39 [5%]; and HR: 12 of 76 [16%]). In a receiver-operating characteristic curve, the new model proved to be an excellent predictor because the area under the curve for the estimated risk is 0.925 (statistical C: 0.925; 95% CI 0.8884 to 0.9539, p <0.0001). In conclusion, the SCD risk prediction model in HC proposed by the 2014 ESC guidelines was validated in our population and represents an improvement compared with previous approaches. A larger multicenter, independent and external validation of the model with long-term follow-up would be advisable. PMID- 27189817 TI - Corrigendum. AB - Deceptive meaning of oxygen uptake measured at the anaerobic threshold in patients with systolic heart failure and atrial fibrillation by Magri et al., European Journal of Preventive Cardiology 2015 22: 1046-1055, DOI: 10.1177/2047487314551546. PMID- 27189818 TI - All-inorganic colloidal silicon nanocrystals-surface modification by boron and phosphorus co-doping. AB - Si nanocrystals (Si-NCs) with extremely heavily B- and P-doped shells are developed and their structural and optical properties are studied. Unlike conventional Si-NCs without doping, B and P co-doped Si-NCs are dispersible in alcohol and water perfectly without any surface functionalization processes. The colloidal solution of co-doped Si-NCs is very stable and no precipitates are observed for more than 5 years. The co-doped colloidal Si-NCs exhibit size controllable photoluminescence (PL) in a very wide energy range covering 0.85 to 1.85 eV. In this paper, we summarize the structural and optical properties of co doped Si-NCs and demonstrate that they are a new type of environmentally-friendly nano-light emitter working in aqueous environments in the visible and near infrared (NIR) ranges. PMID- 27189820 TI - Women's health: a new global agenda. AB - Robyn Norton is co-founder and Principal Director of The George Institute for Global Health (Australia), a not-for-profit medical research institute that aims to increase the provision of safe, effective and affordable healthcare, especially for disadvantaged populations worldwide. She is Professor of Global Health and James Martin Fellow at the University of Oxford (UK), Professor of Public Health at the University of Sydney (Australia) and Honorary Professor at Peking University (China). Professor Norton is internationally regarded for her research on the causes, prevention and management of injuries and the management of various critical conditions in surgical and intensive care settings. She has had a long-standing commitment to improving women's health, particularly in resource-poor environments. PMID- 27189819 TI - The Relationship Between Gene Polymorphisms and Dipping Profile in Patients With Coronary Heart Disease. AB - BACKGROUND: The aim of this study is to report the relationship between certain single-nucleotide polymorphisms (SNPs) and blunted nighttime blood pressure (BP) fall in patients with coronary artery disease confirmed by coronary angiography. METHODS: According to the percentage decrease in mean systolic BP (SBP) and diastolic BP (DBP) during the nighttime period, subjects were classified as dippers or nondippers (nighttime relative SBP or DBP decline >=10% and <10%, respectively). Genetic risk score (GRS18) was constructed to evaluate additive effect of 18 SNPs for nondipping status. RESULTS: In the present study, 1,345 subjects with coronary heart disease (CHD) were included. During follow-up period (median 8.3 years, interquartile range 5.3-9.0 years), there were 245 all-cause deaths (18.2%) including 114 cardiovascular deaths (8.5%). There were significant differences in the number of revascularizations between nondippers SBP and DBP and dippers SBP and DBP (48.0% vs. 36.4%, P < 0.01). SNPs of the genes, MIA3, MRAS, PCSK9, SMG6, and ZC3HC1, were related to a higher risk of nondipping SBP and DBP status. CONCLUSIONS: In the present study, polymorphisms of genes related to CHD (MIA3, MRAS, PCSK9, SMG6, and ZC3HC1) were associated with nondipping SBP and DBP profile, and GRS18 was associated with nondipping status. In addition, this profile was related to a higher risk of revascularization. PMID- 27189821 TI - Anorexia nervosa. AB - Anorexia nervosa (AN) is a psychiatric condition characterized by severe weight loss and secondary problems associated with malnutrition. AN predominantly develops in adolescence in the peripubertal period. Without early effective treatment, the course is protracted with physical, psychological and social morbidity and high mortality. Despite these effects, patients are noted to value the beliefs and behaviours that contribute to their illness rather than regarding them as problematic, which interferes with screening, prevention and early intervention. Involving the family to support interventions early in the course of the illness can produce sustained changes; however, those with a severe and/or protracted illness might require inpatient nursing support and/or outpatient psychotherapy. Prevention programmes aim to moderate the overvaluation of 'thinness' and body dissatisfaction as one of the proximal risk factors. The low prevalence of AN limits the ability to identify risk factors and to study the timing and sex distribution of the condition. However, genetic profiles, premorbid features, and brain structures and functions of patients with AN show similarities with other psychiatric disorders and contrast with obesity and metabolic disorders. Such studies are informing approaches to address the neuroadaptation to starvation and the other various physical and psychosocial deficits associated with AN. This Primer describes the epidemiology, diagnosis, screening and prevention, aetiology, treatment and quality of life of patients with AN. PMID- 27189822 TI - An efficient protocol to enhance the extracellular production of recombinant protein from Escherichia coli by the synergistic effects of sucrose, glycine, and Triton X-100. AB - Targeting recombinant proteins at highly extracellular production in the culture medium of Escherichia coli presents a significant advantage over cytoplasmic or periplasmic expression. In this work, a recombinant protein between ZZ protein and alkaline phosphatase (rZZ-AP) was constructed. Because rZZ-AP has the IgG binding capacity and enzymatic activity, it can serve as an immunoreagent in immunoassays. However, only a very small portion of rZZ-AP is generally secreted into the aqueous medium under conventional cultivation procedure. Hence, we emphasized on the optimization of the culture procedures and attempted to dramatically enhance the yield of extracellular rZZ-AP from E. coli HB101 host cells by adding sucrose, glycine, and Triton X-100 in the culture medium. Results showed that the extracellular production of rZZ-AP in the culture medium containing 5% sucrose, 1% glycine, and 1% Triton X-100 was 18.6 mg/l, which was 18.6-fold higher than that without the three chemicals. And the beta galactosidase activity test showed that the increased extracellular rZZ-AP was not due to cell lysis. Further analysis suggested a significant interaction effect among the three chemicals for the enhancement of extracellular production. Ultrastructural analysis indicated that the enhancement may be due to the influence of sucrose, glycine, and Triton X-100 on the periplasmic osmolality, permeability, or integrity of the cell wall, respectively. This proposed approach presents a simple strategy to enhance the extracellular secretion of recombinant proteins in the E. coli system at the process of cell cultivation. PMID- 27189823 TI - Evaluation of the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) classification scheme for diagnosis of cutaneous melanocytic neoplasms: Results from the International Melanoma Pathology Study Group. AB - BACKGROUND: Pathologists use diverse terminology when interpreting melanocytic neoplasms, potentially compromising quality of care. OBJECTIVE: We sought to evaluate the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) scheme, a 5-category classification system for melanocytic lesions. METHODS: Participants (n = 16) of the 2013 International Melanoma Pathology Study Group Workshop provided independent case-level diagnoses and treatment suggestions for 48 melanocytic lesions. Individual diagnoses (including, when necessary, least and most severe diagnoses) were mapped to corresponding MPATH-Dx classes. Interrater agreement and correlation between MPATH-Dx categorization and treatment suggestions were evaluated. RESULTS: Most participants were board certified dermatopathologists (n = 15), age 50 years or older (n = 12), male (n = 9), based in the United States (n = 11), and primary academic faculty (n = 14). Overall, participants generated 634 case-level diagnoses with treatment suggestions. Mean weighted kappa coefficients for diagnostic agreement after MPATH-Dx mapping (assuming least and most severe diagnoses, when necessary) were 0.70 (95% confidence interval 0.68-0.71) and 0.72 (95% confidence interval 0.71 0.73), respectively, whereas correlation between MPATH-Dx categorization and treatment suggestions was 0.91. LIMITATIONS: This was a small sample size of experienced pathologists in a testing situation. CONCLUSION: Varying diagnostic nomenclature can be classified into a concise hierarchy using the MPATH-Dx scheme. Further research is needed to determine whether this classification system can facilitate diagnostic concordance in general pathology practice and improve patient care. PMID- 27189824 TI - Standardized laboratory monitoring with use of isotretinoin in acne. AB - BACKGROUND: Laboratory monitoring for adverse effects to isotretinoin occurs with variability. Standardization of laboratory monitoring practices represents an opportunity to improve quality of care. OBJECTIVE: We sought to develop an evidence-based approach to laboratory monitoring of patients receiving isotretinoin therapy for acne. METHODS: We reviewed laboratory data from 515 patients with acne undergoing 574 courses of isotretinoin from March 2003 to July 2011. Frequency, timing, and severity of abnormalities were determined. RESULTS: Clinically insignificant leukopenia or thrombocytopenia occurred in 1.4% and 0.9% of patients, respectively. Elevated liver transaminases were detected infrequently and not significantly increased compared with baseline detection rates (1.9% vs 1.6% at baseline). Significant elevations occurred with triglyceride (19.3%) and cholesterol (22.8%) levels. The most severe abnormalities were grade 2 (moderate). Mean duration of treatment before abnormalities were detected was 56.3 days for hypertriglyceridemia, 61.9 days for alanine transaminitis, and 50.1 days for hypercholesterolemia. LIMITATIONS: This was a single-center experience examining variable isotretinoin laboratory monitoring practices. CONCLUSIONS: In healthy patients with normal baseline lipid panel and liver function test results, repeated studies should be performed after 2 months of isotretinoin therapy. If findings are normal, no further testing may be required. Routine complete blood cell count monitoring is not recommended. PMID- 27189825 TI - OPA-15406, a novel, topical, nonsteroidal, selective phosphodiesterase-4 (PDE4) inhibitor, in the treatment of adult and adolescent patients with mild to moderate atopic dermatitis (AD): A phase-II randomized, double-blind, placebo controlled study. AB - BACKGROUND: Peripheral leukocytes in patients with atopic dermatitis (AD) have elevated phosphodiesterase-4 activity, which is associated with production of proinflammatory mediators. OPA-15406 is a phosphodiesterase-4 inhibitor with high selectivity for phosphodiesterase-4-B. OBJECTIVES: We sought to assess effectiveness and tolerability of topical OPA-15406 in patients with AD. METHODS: This was a randomized, double-blind, vehicle-controlled, phase-II study. Patients 10 to 70 years of age with mild or moderate AD received topical OPA-15406 0.3% (n = 41), OPA-15406 1% (n = 43), or vehicle (n = 37) twice daily for 8 weeks. RESULTS: The primary end point, Investigator Global Assessment of Disease Severity score of 0 or 1 with greater than or equal to 2-grade reduction, was met at week 4 in the OPA-15406 1% group (P = .0165 vs vehicle). Mean percentage improvement from baseline Eczema Area and Severity Index score for OPA-15406 1% was notable in week 1 (31.4% vs 6.0% for vehicle; P = .0005), even larger in week 2 (39.0% vs 3.0%; P = .0001), and persisted for 8 weeks. Visual analog scale pruritus scores improved from moderate to mild within the first week in the OPA 15406 1% group (36.4% mean change; P = .0011). OPA-15406 levels in blood were negligible. Incidence of adverse events was low, with most events mild in intensity. LIMITATIONS: Further confirmatory phase-III studies are required. CONCLUSION: OPA-15406 ointment may provide an effective therapeutic modality for patients with mild to moderate AD. PMID- 27189826 TI - Urocanic Acid: An Endogenous Regulator of Langerhans Cells. PMID- 27189827 TI - Atopic Dermatitis Is Associated with Less Physical Activity in US Adults. PMID- 27189829 TI - Binding Affinity and Interaction of LL-37 with HLA-C*06:02 in Psoriasis. PMID- 27189828 TI - MYD88 Somatic Mutation Is a Diagnostic Criterion in Primary Cutaneous Large B Cell Lymphoma. PMID- 27189830 TI - Semidominant Inheritance in Olmsted Syndrome. PMID- 27189831 TI - Clonal dissemination of linezolid-resistant Staphylococcus haemolyticus harbouring a G2576T mutation and the cfr gene in an Indian hospital. PMID- 27189832 TI - Contralateral risk reducing mastectomy in patients with sporadic breast cancer. Benefits and hazards. AB - During the last years an improving outcome of breast conserving surgery was observed along with the availability of diagnostic procedures allowing early diagnosis. Nevertheless, women with breast cancer are more frequently requesting a radical approach comprising contralateral mastectomy even if they do not have a demonstrated increased genetic risk. In this paper we reviewed the main reasons patients ask for aggressive preventive surgery, the perceived and the real risks of developing contralateral breast cancer, and the potential, if any, survival benefits along with the hazards associated to contralateral risk reducing mastectomy. A respectful management should be given to these women within a multi disciplinary team. Psychological support is highly encouraged cope fears and uncertainties but treating physicians should provide patients with comprehensive and unbiased data to take the best decision for the single person. Physicians should also give clear information on the benefits of adjuvant therapies which are reducing the incidence of contralateral breast cancer and also of the possible influences of healthy lifestyle (weight control, physical activity, diet) as effective preventive methods. PMID- 27189833 TI - Positron emission tomography (18)F-fluorodeoxyglucose uptake and prognosis in patients with bone and soft tissue sarcoma: A meta-analysis. AB - PURPOSE: To investigate the prognostic significance of (18)F-FDG PET imaging in patients with bone and soft tissue sarcoma, a meta-analysis was conducted. METHODS: Comprehensive literature searches were performed in PubMed, Embase, Web of Science and Cochrane Library. Pooled hazard ratio (HR) values were calculated to assess the correlations of pre-chemotherapy SUV (SUV1), post-chemotherapy SUV (SUV2), SUV Ratio, total lesion glycolysis (TLG) and metabolic tumor volume (MTV) with event-free survival (EFS) and overall survival (OS). RESULTS: Twenty-three studies with 1261 patients were identified. The combined HRs for EFS were 1.84 (95% CI: 1.54-2.20) for SUV1, 2.92 (95% CI: 2.15-3.97) for SUV2, 1.90 (95% CI: 1.43-2.52) for SUV Ratio, 3.01 (95% CI: 1.36-6.67) for TLG and 2.32 (95% CI: 1.44 3.75) for MTV. The pooled HRs for OS were 1.85 (95% CI: 1.49-2.30) for SUV1, 2.00 (95% CI: 1.39-2.88) for SUV2, 2.20 (95% CI: 1.18-4.10) for SUV Ratio, 6.19 (95% CI: 2.17-17.66) for TLG and 2.67 (95% CI: 1.52-4.68) for MTV. Besides, high SUV1 was found to be significantly associated with higher rate of metastasis (RR 5.55, 95% CI: 2.75-11.18) and local recurrence (RR 1.87 95% CI: 1.28-2.72). CONCLUSION: (18)F-FDG PET parameters of SUV1, SUV2, SUV Ratio, TLG and MTV may have effective prognostic significance for patients with bone and soft tissue sarcoma. (18)F-FDG PET imaging may be a promising tool to help predict survival outcomes of these patients. PMID- 27189835 TI - Corrigendum. AB - Pedro-Rosa, L.; Buckner, F.; Ranade, R. M.; et al. Identification of Potent Inhibitors of the Trypanosoma brucei Methionyl-tRNA Synthetase via High Throughput Orthogonal Screening. J Biomol Screen 2015: , 20, 122-130. (Original DOI: 10.1177/1087057114548832). PMID- 27189834 TI - Tin phosphide-based anodes for sodium-ion batteries: synthesis via solvothermal transformation of Sn metal and phase-dependent Na storage performance. AB - There is a great deal of current interest in the development of rechargeable sodium (Na)-ion batteries (SIBs) for low-cost, large-scale stationary energy storage systems. For the commercial success of this technology, significant progress should be made in developing robust anode (negative electrode) materials with high capacity and long cycle life. Sn-P compounds are considered promising anode materials that have considerable potential to meet the required performance of SIBs, and they have been typically prepared by high-energy mechanical milling. Here, we report Sn-P-based anodes synthesised through solvothermal transformation of Sn metal and their electrochemical Na storage properties. The temperature and time period used for solvothermal treatment play a crucial role in determining the phase, microstructure, and composition of the Sn-P compound and thus its electrochemical performance. The Sn-P compound prepared under an optimised solvothermal condition shows excellent electrochemical performance as an SIB anode, as evidenced by a high reversible capacity of ~560 mAh g(-1) at a current density of 100 mA g(-1) and cycling stability for 100 cycles. The solvothermal route provides an effective approach to synthesising Sn-P anodes with controlled phases and compositions, thus tailoring their Na storage behaviour. PMID- 27189836 TI - Mean Platelet Volume, Platelet Distribution Width, and Platelet Count in Varicocele: A Systematic Review and Meta-Analysis. AB - BACKGROUND/AIMS: The aim of this study was to elucidate the usefulness of platelet indices, mean platelet volume (MPV), platelet distribution width (PDW), and platelet count in diagnosis and monitoring of varicocele. METHODS: The current study included 525 patients and 379 healthy subjects from five eligible studies. We performed meta-analysis of MPV, PDW, and platelet count and mean differences in these platelet indices between healthy subjects and varicocele patients. RESULTS: The pooled MPVs were 8.168 fL (95% confidence interval [CI] 7.589 to 8.747) and 8.801 fL (95% CI 8.028 to 9.574) in healthy subjects and varicocele patients, respectively. The pooled mean difference in MPV between healthy subjects and varicocele patients was 0.834 fL in case-control studies (95% CI 0.195 to 1.473, P = 0.011). In both healthy subjects and varicocele patients, low platelet count subgroups showed higher MPV than high platelet count subgroups. The mean difference in MPV was higher in low platelet count subgroup. There was no significant difference in PDW between healthy subjects and varicocele patients. CONCLUSION: Taken together, our data showed that platelet count was significantly lower in varicocele patients than in healthy subjects. Varicocele patients showed significantly higher MPV and lower platelet count than healthy subjects. MPV levels of patients differed according to platelet counts. PMID- 27189838 TI - "Weariness" and "unpleasantness" reduce adherence to branched-chain amino acid granules among Japanese patients with liver cirrhosis: results of a single-center cross-sectional survey. AB - AIM: Branched-chain amino acids (BCAA) are valuable in the treatment of liver cirrhosis because they increase serum albumin levels. Poor adherence to BCAA may adversely affect prognosis, but little is known about factors predicting adherence. We undertook a survey of patients prescribed BCAA for the treatment of cirrhosis. METHODS: Pharmacists carried out face-to-face interviews with patients (or their representatives) prescribed any of nine BCAA formulations. Question categories included patient characteristics, prescription of BCAA granules, and perceptions of BCAA administration, including adherence and possible factors that might impact adherence. "Poor adherence" was defined as "not taking the medication appropriately" or "forgetting to take the medication". RESULTS: Overall, 253 patients (or representatives) completed the survey, of whom 135 were men, 114 were women, and 148 were >=70 years old. Most patients (163) were prescribed BCAA for >=2 years and were using three packs per day. Thirty-two patients did not take their medication appropriately and 69 sometimes forgot to administer it. Weariness of taking the medication (P < 0.001) and the perceived unpleasantness (P = 0.023) of the medication in terms of its taste and volume were significantly associated with poor adherence. The patients reported that the most influential educators were general practitioners, followed by certified hepatologists, then pharmacists. CONCLUSION: Most patients had good adherence to BCAA in clinical practice. Poor adherence was associated with weariness with taking medication, and the unpleasantness of the medication itself. Patient education from general practitioners and hepatologists combined with adherence counseling from pharmacists may help improve adherence. PMID- 27189839 TI - Breastfeeding beyond infancy: a concept analysis. AB - AIM: To report an analysis of the concept of breastfeeding beyond infancy. BACKGROUND: The World Health Organization and Health Canada recommends breastfeeding is sustained until 2 years old and beyond. However, little is known about breastfeeding a child beyond 12 months old. Breastfeeding beyond infancy is defined as any breastfeeding over the age of 12 months with no parameters placed on who initiates the weaning process. DESIGN: Rodger's framework of concept analysis was used to organize and guide data analysis. DATA SOURCES: A historical, systematic search of the literature up until 2014 was conducted using the search terms: breastfeeding OR breast feeding OR breast-feeding AND sustained, extended, prolonged, long-term and duration. METHODS: Literature was selected according to whether breastfeeding beyond 12 months old was described or analysed. All study designs and observational, descriptive and opinion papers were included in the initial screenings. RESULTS: Four characteristics were chosen as essential attributes of breastfeeding beyond infancy: health benefits, maternal profiles, parenting style and experiences. Consequences included stigma and secrecy. Additionally, the role of the nurse in supporting breastfeeding beyond infancy was explored. CONCLUSIONS: The practice of breastfeeding beyond infancy is entrenched in parenting beliefs that serve to address the child's needs by fostering an intimate and attached relationship between the mother and child. Many women conceal their breastfeeding behaviour to protect themselves from unsolicited judgement and comments. Nurses are well-served to understand, support and promote the practice of breastfeeding beyond infancy to ensure the bio-psycho-social health of their clients. PMID- 27189840 TI - Phytochemical profile of three Ballota species essential oils and evaluation of the effects on human cancer cells. AB - Three Ballota species, Ballota undulata, Ballota saxatilis and Ballota nigra ssp. foetida, were investigated for their cytotoxicity against two human cancer cells, hepatoma HepG2 cell line and breast cancer MCF-7 cell line, and for their antioxidant activity. The chemical composition of essential oils was studied by GC and GC-MS. Sesquiterpenes were the main constituents. The most antiproliferative essential oil against HepG2 cells was B. undulata with a percentage of inhibition of 81.36 +/- 3.54 at a concentration of 100 MUg/mL, while against MCF-7 cells essential oil from B. saxatilis was the most active with a percentage of inhibition of 24.18 +/- 1.13 at a concentration of 100 MUg/mL. The antioxidant activity was investigated by DPPH test for all the oils. B. undulata showed the highest antiradical effect, with IC50 value of 529.7 +/- 37.4 MUg/mL. PMID- 27189837 TI - Urokinase links plasminogen activation and cell adhesion by cleavage of the RGD motif in vitronectin. AB - Components of the plasminogen activation system including urokinase (uPA), its inhibitor (PAI-1) and its cell surface receptor (uPAR) have been implicated in a wide variety of biological processes related to tissue homoeostasis. Firstly, the binding of uPA to uPAR favours extracellular proteolysis by enhancing cell surface plasminogen activation. Secondly, it promotes cell adhesion and signalling through binding of the provisional matrix protein vitronectin. We now report that uPA and plasmin induces a potent negative feedback on cell adhesion through specific cleavage of the RGD motif in vitronectin. Cleavage of vitronectin by uPA displays a remarkable receptor dependence and requires concomitant binding of both uPA and vitronectin to uPAR Moreover, we show that PAI-1 counteracts the negative feedback and behaves as a proteolysis-triggered stabilizer of uPAR-mediated cell adhesion to vitronectin. These findings identify a novel and highly specific function for the plasminogen activation system in the regulation of cell adhesion to vitronectin. The cleavage of vitronectin by uPA and plasmin results in the release of N-terminal vitronectin fragments that can be detected in vivo, underscoring the potential physiological relevance of the process. PMID- 27189841 TI - Evaluation of thermal conductivity and flexural strength properties of poly(methyl methacrylate) denture base material reinforced with different fillers. AB - STATEMENT OF PROBLEM: Poly(methyl methacrylate) (PMMA) is widely used in prosthodontics as a denture base material. However, it has several disadvantages, including low strength and low thermal conductivity. PURPOSE: The purpose of this in vitro study was to evaluate thermal conductivity and flexural strength after adding powdered Ag, TiO2, ZrO2, Al2O3, SiC, SiC-nano, Si3N4, and HA-nano in ratios of 10 wt% to PMMA. MATERIAL AND METHODS: A total of 144 specimens were fabricated and divided into 18 groups. Specimens were left in water for 30 days. Thermal conductivity values were measured using a heat flowmeter, flexural strength was measured with a 3-point bend test, and specimens were investigated with environmental scanning electron microscopy. One-way ANOVA was used to compare means followed by using Duncan multiple range test (alpha=.05). RESULTS: The thermal conductivity value of PMMA increased significantly after the addition of Si3N4, SiC, Al2O3, SiC-nano, TiO2, ZrO2, HA-nano, and Ag. Progressive increases in thermal conductivity were observed in Si3N4, SiC, and Al2O3 fillers. Flexural strength values of the control group were not significantly different from those of the SiC, Al2O3, or Ag group (P>.05). In the other groups, flexural strength values decreased significantly (P<.05). On the basis of electron microscopy, we observed that Si3N4, SiC, and Al2O3 powders had higher thermal conductivity values that are dissipated more homogeneously in PMMA. CONCLUSIONS: Although the addition of 10 wt% SiC, Al2O3, and Ag powder to PMMA significantly increased thermal conductivity, the flexural strength values of PMMA were not significantly changed. PMID- 27189842 TI - Cross-linked Composite Gel Polymer Electrolyte using Mesoporous Methacrylate Functionalized SiO2 Nanoparticles for Lithium-Ion Polymer Batteries. AB - Liquid electrolytes composed of lithium salt in a mixture of organic solvents have been widely used for lithium-ion batteries. However, the high flammability of the organic solvents can lead to thermal runaway and explosions if the system is accidentally subjected to a short circuit or experiences local overheating. In this work, a cross-linked composite gel polymer electrolyte was prepared and applied to lithium-ion polymer cells as a safer and more reliable electrolyte. Mesoporous SiO2 nanoparticles containing reactive methacrylate groups as cross linking sites were synthesized and dispersed into the fibrous polyacrylonitrile membrane. They directly reacted with gel electrolyte precursors containing tri(ethylene glycol) diacrylate, resulting in the formation of a cross-linked composite gel polymer electrolyte with high ionic conductivity and favorable interfacial characteristics. The mesoporous SiO2 particles also served as HF scavengers to reduce the HF content in the electrolyte at high temperature. As a result, the cycling performance of the lithium-ion polymer cells with cross linked composite gel polymer electrolytes employing methacrylate-functionalized mesoporous SiO2 nanoparticles was remarkably improved at elevated temperatures. PMID- 27189843 TI - Increased prevalence of Pneumocystis jirovecii colonisation in acute pulmonary exacerbations of cystic fibrosis. AB - OBJECTIVES: This study examined the prevalence of Pneumocystis jirovecii in the sputum of adults with cystic fibrosis during clinical stability and acute pulmonary exacerbation. METHODS: This was a prospective, longitudinal observational study of patients attending the Manchester Adult Cystic Fibrosis Centre. Sputum samples were analysed for P. jirovecii DNA using PCR at enrolment and up to 5 follow-up visits. Patients were classified as stable or exacerbating using a modified Fuch's pulmonary exacerbation score. RESULTS: 226 samples were tested from 111 patients. P. jirovecii was more likely to be detected in samples at acute pulmonary exacerbation (7/76 (9.2%)) compared with stable visits (3/150 (2%)), p = 0.03. P. jirovecii was detected less frequently if patients had received co-trimoxazole within 3 months of sample collection (0% versus 29.7%, p = 0.03). CONCLUSIONS: Prevalence of P. jirovecii in stable patients is low, but P. jirovecii is detected in approximately 1 in 10 patients experiencing an acute pulmonary exacerbation. PMID- 27189844 TI - Healing of tibial bone tunnels after bone grafting for staged revision anterior cruciate ligament surgery: A prospective computed tomography analysis. AB - AIM: To quantify healing of tibial bone tunnels after bone grafting in two-stage ACL reconstruction revision. METHODS: Ten consecutive patients underwent autogenous bone grafting prior to ACL reconstruction revision (four females and six males, average age 28years). The indications for two-stage surgery were as follows: (1) the enlargement of the tibial tunnel aperture was >20mm in diameter or, (2) the existing tunnel was overlapped with the optimal tunnel and positioned more than a half tunnel diameter posterior to the optimal position. An autogenous iliac bone block was driven into a new tunnel. CT examinations were performed at three, 12 and 24weeks after bone grafting. Evaluations were performed on 15 axial planes at one-millimeter intervals from the articular surface perpendicular to the long axis of the tibia using the following three parameters: occupying ratio (OR), union ratio (UR), and bone mineral density (BMD) of grafted bone. RESULTS: The average ORs were 81, 85 and 94%, and the average URs were 49, 75 and 89% at three, 12 and 24weeks, respectively. Each parameter significantly increased over time. The average BMD was 510 and 571mg/cm(3) at 12 and 24weeks, respectively, with a significantly higher value at 24weeks. CONCLUSION: The average ORs, URs and BMD at 24weeks after bone grafting were higher than those at 12weeks, which suggests that at 24weeks after bone grating, the condition of the patients' beds becomes favorable for safe implantation and fixation of ACL graft revision. LEVEL OF EVIDENCE: Case series Level IV. PMID- 27189845 TI - Reply to "The origin of the abnormal muscle response seen in hemifacial spasm remains controversial". PMID- 27189846 TI - Reply to "The usefulness of diffusion tensor tractography for estimating the state of corticobulbar tract in stroke patients". PMID- 27189847 TI - Spatial characteristics of professional tennis serves with implications for serving aces: A machine learning approach. AB - This study sought to determine the features of an ideal serve in men's professional tennis. A total of 25,680 first serves executed by 151 male tennis players during Australian Open competition were classified as either aces or returned into play. Spatiotemporal (impact location, speed, projection angles, landing location and relative player locations) and contextual (score) features of each serve were extracted from Hawk-Eye data and used to construct a classification tree model (with decision rules) that predicted serve outcome. k means clustering was applied to the landing locations to quantify optimal landing locations for aces. The classification tree revealed that (1) serve directionality, relative to the returner; (2) the ball's landing proximity to the nearest service box line and (3) serve speed classified aces with an accuracy of 87.02%. Hitting aces appeared more contingent on accuracy than speed, with serves directed >5.88 degrees from the returner and landing <15.27 cm from a service box line most indicative of an ace. k-means clustering revealed four distinct locations (~0.73 m wide * 2.35 m deep) in the corners of the service box that corresponded to aces. These landing locations provide empirically derived target locations for players to adhere to during practice and competition. PMID- 27189849 TI - Battle of the experts: Providers - 1, Government - 0! PMID- 27189848 TI - An integrative review of physical activity/exercise intervention effects on function and health-related quality of life in older adults with heart failure. AB - This paper reviews randomized, controlled trials (RCTs) that have used a physical activity/exercise intervention in older adults with heart failure and reported outcomes of physical function and/or health-related quality of life. An integrative review was necessary because a literature search indicated no reviews have been done regarding these outcomes which are deemed very important by the older adult population. Computerized database search strategies by authors between 2002 and 2015 resulted in 163 studies, with 12 meeting inclusion criteria. Interventions were performed in clinic and home-based, group and/or individual settings with durations from three to 12 months. Interventions were varied. Common methodological weaknesses of the studies include lack of theory guiding the intervention, small sample and low minority representation. Strengths included detailed intervention methods. There was a moderate effect of interventions with no reported adverse effects. Further work is essential to identify successful strategies to support older adults with heart failure to increase their physical activity levels. PMID- 27189850 TI - A proof-of-concept study of the VeinScrew: A new percutaneous venous closure device. AB - Objective This study evaluated the concept of percutaneous closure of insufficient veins using the VeinScrew principle. Methods The VeinScrew is designed to place a spring-shaped implant that contracts and clamps around the vein. The ability of the device to occlude adequately was tested in a bench model experiment. The feasibility of accurate placement and adequate venous occlusion was evaluated in an animal experiment and in a human cadaveric experiment. Results The VeinScrew implant occluded up to a pressure of 135 mmHg. In vivo studies confirmed that deployment was challenging but technically feasible, and subsequent phlebography showed closure of the vein. The cadaveric study showed that percutaneous placement of the evolved VeinScrew around the great saphenous vein was feasible and accurate. Conclusions The current studies show the feasibility of the VeinScrew concept. Future developments and translational studies are necessary to determine the potential of this technique as a new option in the phlebologist's toolbox. PMID- 27189851 TI - Vitiligo. AB - Vitiligo is an acquired depigmenting disorder that affects 0.5% to 2% of the world population. Three different forms are classified according to the distribution of lesions; namely non-segmental, segmental and mixed vitiligo. Vitiligo is associated with polymorphisms in genes involved in the immune response and in melanogenesis. However, environmental factors are required for the development of manifest disease. In general, the diagnosis is clinical and no laboratory tests or biopsies are required. Metabolic alterations are central to current concepts in pathophysiology. They induce an increased generation of reactive oxygen species and susceptibility to mild exogenous stimuli in the epidermis. This produces a senescent phenotype of skin cells, leads to the release of innate immune molecules, which trigger autoimmunity, and ultimately causes dysfunction and death of melanocytes. Clinical management aims to halt depigmentation, and to either repigment or depigment the skin, depending on the extent of disease. New therapeutic approaches include stimulation of melanocyte differentiation and proliferation through alpha-melanocyte-stimulating hormone analogues and through epidermal stem cell engineering. Several questions remain unsolved, including the connection between melanocyte depletion and stem cell exhaustion, the underlying degenerative mechanisms and the biological mediators of cell death. Overall, vitiligo is an excellent model for studying degenerative and autoimmune processes and for testing novel approaches in regenerative medicine. For an illustrated summary of this Primer, visit: http://go.nature.com/vIhFSC. PMID- 27189852 TI - Paramedics' experiences of end-of-life care decision making with regard to nursing home residents: an exploration of influential issues and factors. AB - INTRODUCTION: For a patient nearing the end of his or her life, transfer from a nursing home to the ED can be inappropriate, with potentially negative consequences, but transfer in these circumstances is, regrettably, all too common. There is a lack of published literature exploring how paramedics make decisions in end-of-life care situations. This study aims to explore how paramedics make decisions when asked to transport nursing home residents nearing the end of their lives. METHODS: Phenomenological influenced design with a pragmatic approach. Semi-structured face-to-face interviews were conducted with six paramedics in an English NHS Ambulance Trust and subsequent data collected by text message. Audio-recorded interviews were transcribed verbatim and analysed using a thematic approach. RESULTS: Three themes emerged in relation to the decision to transport patients from nursing homes to EDs in end-of-life care situations. Paramedics identified difficulties in understanding nursing home residents' wishes. When a patient no longer had the capacity for decision making, paramedics' reasoning processes were aligned to best interest decision making, weighing the risks and benefits of hospitalisation. Paramedics found it challenging to balance patients' best interests with pressure from others: nursing staff, patients' relatives and colleagues. CONCLUSIONS: A range of factors influence paramedics' decisions to transport nursing home residents to EDs in end-of-life care situations. Decision making became a process of negotiation when the patient's perceived best interests conflicted with that of others, resulting in contrasting approaches by paramedics. This paper considers how paramedics might be better trained and supported in dealing with these situations, with the aim of providing dignified and appropriate care to patients as they reach the end of their lives. PMID- 27189854 TI - Demographic correlates of medication knowledge in Hong Kong early psychosis patients. AB - AIM: Patient knowledge of prescribed medications is important for accurate medication consumption. Not many studies have identified the demographic correlates of medication knowledge in psychiatric patients, and fewer have performed so for non-Western societies, which may present different results owing to distinct cultural factors. Our objective was to identify the demographic correlates of medication knowledge in early psychosis patients from Hong Kong. METHODS: A short questionnaire comprising questions on six components of medication knowledge was administered to 105 consecutive early psychosis patients from an outpatient clinic in Hong Kong. A suite of patient demographics was assembled from clinicians' records. RESULTS: Poor medication knowledge was characterized by patients of older age (>30 years), low education level (<=Form 3), overall negative family relationships (as compared with overall positive ones) and shorter treatment duration (<=4 years). Shorter treatment duration most consistently predicted poor medication knowledge, displaying significant (P < 0.05) associations with four out of six knowledge components. Patients (54.3%) did not know the English names of their medication. CONCLUSIONS: Specific groups of early psychosis patients are at risk of having poor medication knowledge; these individuals should be identified to receive regular health education. Contrary to findings from non-psychosis groups, short treatment duration was unequivocally associated with poorer medication knowledge in patients with early psychosis. Local replacements for English medication names should be considered in non-English speaking societies, especially in areas of mental health treatment. PMID- 27189855 TI - Nonadherence to therapy after adult solid organ transplantation: A focus on risks and mitigation strategies. PMID- 27189856 TI - Revision of the International Pharmaceutical Federation's Basel Statements on the future of hospital pharmacy: From Basel to Bangkok. AB - PURPOSE: The processes used to revise the 2008 Basel Statements on the future of hospital pharmacy are summarized, and the revised statements are presented. METHODS: The process for revising the Basel Statements followed an approach similar to that used during their initial development. The Hospital Pharmacy Section (HPS) of the International Pharmaceutical Federation (FIP) revised the 2008 FIP Basel Statements in four phases, including a survey of hospital pharmacists worldwide, an internal review, online forums, and a face-to-face "World Cafe" workshop in Bangkok, Thailand. RESULTS: The global survey on the initial Basel Statements included input from 334 respondents from 62 countries. The majority of respondents agreed that most of the initial Basel Statements were acceptable as written and did not require revision. In total, 11 statements were judged by more than 10% of respondents as needing revision or deletion. The FIP HPS executive committee used the survey results to develop 69 initial revised draft statements. After an online discussion with the international hospital pharmacy community, including individuals from 28 countries representing all six World Health Organization regions, a final set of draft statements was prepared for the live discussion involving participants from 20 countries. The final 65 revised Basel Statements were voted on and accepted. CONCLUSION: Systematic revision of the FIP Basel Statements resulted in an updated reflection of aspirational goals for the future of hospital pharmacy practice. While this revision reflects the development of new goals for hospital pharmacy practice, the core principles of the Basel Statements remain an essential foundation for the discipline. PMID- 27189857 TI - Doxorubicin-loaded galactose-conjugated poly(d,l-lactide-co-glycolide) nanoparticles as hepatocyte-targeting drug carrier. AB - The objective of this work is to produce doxorubicin-loaded galactose-conjugated poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) to be specifically recognised by human hepatoma cellular carcinoma (Hep G2) cells and assess NPs cytotoxicity. Doxorubicin-unloaded and doxorubicin-loaded galactose-conjugated PLGA NPs were prepared using an emulsion method and characterised for morphology, size, drug release behaviour, Hep G2 recognition and cell cytotoxicity. The produced doxorubicin-loaded PLGA-galactose-conjugate nanoparticles (PLGA-GAL NPs) are spherical in shape with a size of 365 +/- 74 nm, a drug encapsulation efficiency of 69% and released in a biphasic pattern with higher release rates at pH 5. In vitro cell studies confirmed the specific interaction between the receptors of Hep G2 and the PLGA-GAL NPs. Cell cytotoxicity tests showed that unloaded NPs are non-toxic and that doxorubicin-loaded NPs caused a cellular viability decrease of around 80%, therefore representing a promising approach to improve liver-specific drug delivery. PMID- 27189858 TI - Immortalized bovine mammary epithelial cells express stem cell markers and differentiate in vitro. AB - The bovine mammary epithelial cell is a secretory cell, and its cell number and secretory activity determine milk production. In this study, we immortalized a bovine mammary epithelial cell line by SV40 large T antigen gene using a retrovirus based on Chinese Holstein primary mammary epithelial cells (CMEC) cultured in vitro. An immortalized bovine mammary epithelial cell line surpassed the 50-passage mark and was designated the CMEC-H. The immortalized mammary epithelial cells grew in close contact with each other and exhibited the typical cobblestone morphology characteristic with obvious boundaries. The telomerase expression of CMEC-H has consistently demonstrated the presence of telomerase activity as an immortalized cell line, but the cell line never induced tumor formation in nude mice. CMEC-H expressed epithelial (cytokeratins CK7, CK8, CK18, and CK19), mesenchymal (vimentin), and stem/progenitor (CD44 and p63) cell markers. The induced expression of milk proteins, alphaS1 -casein, beta-casein, kappa-casein, and butyrophilin, indicated that CMEC-H maintained the synthesis function of the mammary epithelial cells. The established immortalized bovine mammary epithelial cell line CMEC-H is capable of self-renewal and differentiation and can serve as a valuable reagent for studying the physiological mechanism of the mammary gland. PMID- 27189859 TI - Penfluridol suppresses pancreatic tumor growth by autophagy-mediated apoptosis. AB - Pancreatic tumors exhibit enhanced autophagy as compared to any other cancer, making it resistant to chemotherapy. We evaluated the effect of penfluridol against pancreatic cancer. Penfluridol treatment induced apoptosis and inhibited the growth of Panc-1, BxPC-3 and AsPC-1, pancreatic cancer cells with IC50 ranging between 6-7 MUM after 24 h of treatment. Significant autophagy was induced by penfluridol treatment in pancreatic cancer cells. Punctate LC3B and autophagosomes staining confirmed autophagy. Inhibiting autophagy by chloroquine, bafilomycin, 3-methyladenine or LC3BsiRNA, significantly blocked penfluridol induced apoptosis, suggesting that autophagy lead to apoptosis in our model. Penfluridol treatment suppressed the growth of BxPC-3 tumor xenografts by 48% as compared to 17% when treated in combination with chloroquine. Similarly, penfluridol suppressed the growth of AsPC-1 tumors by 40% versus 16% when given in combination with chloroquine. TUNEL staining and caspase-3 cleavage revealed less apoptosis in the tumors from mice treated with penfluridol and chloroquine as compared to penfluridol alone. Penfluridol treatment also suppressed the growth of orthotopically implanted Panc-1 tumors by 80% by inducing autophagy mediated apoptosis in the tumors. These studies established that penfluridol inhibits pancreatic tumor growth by autophagy-mediated apoptosis. Since penfluridol is already in clinic, positive findings from our study will accelerate its clinical development. PMID- 27189861 TI - The preservation of living cells with biocompatible microparticles. AB - Biomedical applications of living cells have rapidly expanded in many fields such as toxic detection, drug screening, and regenerative medicine, etc. Efficient methods to support cell survival and maintain activity in vitro have become increasingly important. However, traditional cryopreservation for living cell based applications is limited by several problems. Here, we report that magnetic hydrogel microparticles can physically assemble into a 3D environment for efficient cell preservation in physiological conditions, avoiding any chemical reactions that would damage the cells. Two representative cell lines (loosely and firmly adherent) were tested to evaluate the versatility of this method. The results showed that cell longevity was significantly extended to at least 15 days, while the control cell samples without microparticles quickly died within 3 days. Moreover, after preservation, cells can be easily retrieved by applying a magnet to separate the magnetic particles. This strategy can also inhibit cell over-proliferation while avoiding the use of temperature extremes or toxic cryoprotectants that are essential in cryopreservation. PMID- 27189853 TI - Microglia-Neuron Communication in Epilepsy. AB - Epilepsy has remained a significant social concern and financial burden globally. Current therapeutic strategies are based primarily on neurocentric mechanisms that have not proven successful in at least a third of patients, raising the need for novel alternative and complementary approaches. Recent evidence implicates glial cells and neuroinflammation in the pathogenesis of epilepsy with the promise of targeting these cells to complement existing strategies. Specifically, microglial involvement, as a major inflammatory cell in the epileptic brain, has been poorly studied. In this review, we highlight microglial reaction to experimental seizures, discuss microglial control of neuronal activities, and propose the functions of microglia during acute epileptic phenotypes, delayed neurodegeneration, and aberrant neurogenesis. Future research that would help fill in the current gaps in our knowledge includes epilepsy-induced alterations in basic microglial functions, neuro-microglial interactions during chronic epilepsy, and microglial contribution to developmental seizures. Studying the role of microglia in epilepsy could inform therapies to better alleviate the disease. GLIA 2016;65:5-18. PMID- 27189862 TI - Prevalence of alpha(+)-Thalassemia in the Scheduled Tribe and Scheduled Caste Populations of Damoh District in Madhya Pradesh, Central India. AB - This study was carried out to ascertain the allelic frequency of alpha(+) thalassemia (alpha(+)-thal) in Scheduled caste and scheduled tribe populations of the Damoh district of Madhya Pradesh, India. Random blood samples of Scheduled tribe (267) and Scheduled caste (168), considering the family as a sampling unit, were analyzed for the presence of the -alpha(3.7) (rightward) (NG_000006.1: g.34164_37967del3804) and -alpha(4.2) (leftward) (AF221717) deletions. alpha(+) Thal was significantly higher in the Scheduled tribals (77.9%) as compared to the scheduled caste population (9.0%). About 58.0% scheduled tribals carried at least one chromosome with the -alpha(3.7) deletion and 20.0% scheduled tribals carried the -alpha(4.2) deletion. Frequency for the -alpha(3.7) allele was 0.487 in the scheduled tribal populations in comparison to 0.021 in scheduled castes. Allelic frequency for -alpha(4.2) was 0.103 and 0.024, respectively, in the above communities. No Hardy-Weinberg equilibrium for alpha-thal gene (p < 0.05) was detected in the tribal population, indicating the presence of selection pressures in favor of alpha-thal mutation and adaptation. PMID- 27189860 TI - Blood group A and D negativity are associated with symptomatic West Nile virus infection. AB - BACKGROUND: West Nile virus (WNV) infection is mostly asymptomatic (AS) but 20% of subjects report WNV fever and 1% of patients experience neurologic diseases with higher rates in elderly and immunosuppressed persons. With no treatment and no vaccine to prevent the development of symptomatic (S) infections, it is essential to understand prognostic factors influencing S disease outcome. Host genetic background has been linked to the development of WNV neuroinvasive disease. This study investigates the association between the ABO and D blood group status and WNV disease outcome. STUDY DESIGN AND METHODS: The distribution of blood groups was investigated within a cohort of 374 WNV+ blood donors including 244 AS and 130 S WNV+ blood donors. Logistic regression analyses were used to examine associations between A, B, O, and D blood groups and WNV clinical disease outcome. RESULTS: S WNV+ donors exhibited increased frequencies of blood group A (S 47.6%, AS 36.8%, p = 0.04; odds ratio [OR], 1.56; 95% confidence interval [CI], 1.01-2.40) and D- individuals (S 21.5%, AS 13.1%, p = 0.03; OR, 1.82; 95% CI, 1.04-3.18). CONCLUSION: The findings suggest a genetic susceptibility placing blood group A and D- individuals at risk for the development of S disease outcome after WNV infection. PMID- 27189863 TI - Chronic obstructive pulmonary disease. AB - Chronic obstructive pulmonary disease (COPD) is a common disease with high global morbidity and mortality. COPD is characterized by poorly reversible airway obstruction, which is confirmed by spirometry, and includes obstruction of the small airways (chronic obstructive bronchiolitis) and emphysema, which lead to air trapping and shortness of breath in response to physical exertion. The most common risk factor for the development of COPD is cigarette smoking, but other environmental factors, such as exposure to indoor air pollutants - especially in developing countries - might influence COPD risk. Not all smokers develop COPD and the reasons for disease susceptibility in these individuals have not been fully elucidated. Although the mechanisms underlying COPD remain poorly understood, the disease is associated with chronic inflammation that is usually corticosteroid resistant. In addition, COPD involves accelerated ageing of the lungs and an abnormal repair mechanism that might be driven by oxidative stress. Acute exacerbations, which are mainly triggered by viral or bacterial infections, are important as they are linked to a poor prognosis. The mainstay of the management of stable disease is the use of inhaled long-acting bronchodilators, whereas corticosteroids are beneficial primarily in patients who have coexisting features of asthma, such as eosinophilic inflammation and more reversibility of airway obstruction. Apart from smoking cessation, no treatments reduce disease progression. More research is needed to better understand disease mechanisms and to develop new treatments that reduce disease activity and progression. PMID- 27189864 TI - Apoptosis of Corneal Epithelial Cells Caused by Ultraviolet B-induced Loss of K(+) is Inhibited by Ba(2.). AB - UVB exposure at ambient outdoor levels triggers rapid K(+) loss and apoptosis in human corneal limbal epithelial (HCLE) cells cultured in medium containing 5.5 mM K(+), but considerably less apoptosis occurs when the medium contains the high K(+) concentration that is present in tears (25 mM). Since Ba(2+) blocks several K(+) channels, we tested whether Ba(2+)-sensitive K(+) channels are responsible for some or all of the UVB-activated K(+) loss and subsequent activation of the caspase cascade and apoptosis. Corneal epithelial cells in culture were exposed to UVB at 80 or 150 mJ/cm(2). Patch-clamp recording was used to measure UVB induced K(+) currents. Caspase-activity and TUNEL assays were performed on HCLE cells exposed to UVB followed by incubation in the presence or absence of Ba(2+). K(+) currents were activated in HCLE cells following UVB-exposure. These currents were reversibly blocked by 5 mM Ba(2+). When HCLE cells were incubated with 5 mM Ba(2+) after exposure to UVB, activation of caspases-9, -8, and -3 and DNA fragmentation were significantly decreased. The data confirm that UVB-induced K(+) current activation and loss of intracellular K(+) leads to activation of the caspase cascade and apoptosis. Extracellular Ba(2+) inhibits UVB-induced apoptosis by preventing loss of intracellular K(+) when K(+) channels are activated. Ba(2+) therefore has effects similar to elevated extracellular K(+) in protecting HCLE cells from UVB-induced apoptosis. This supports our overall hypothesis that elevated K(+) in tears contributes to protection of the corneal epithelium from adverse effects of ambient outdoor UVB. PMID- 27189866 TI - Contributions of the lower dimer to supramolecular actin patterning revealed by TIRF microscopy. AB - Two distinct dimers are formed during the initial steps of actin polymerization. The first one, referred to as the 'lower dimer' (LD) was discovered many years ago by means of chemical crosslinking. Owing to its transient nature, a biological relevance had long been precluded when, using LD-specific antibodies, we detected LD-like contacts in actin assemblies that are associated with the endolysosomal compartment in a number of different cell lines. Moreover, immunofluorescence showed the presence of LD-related structures at the cell periphery of migrating fibroblasts, in the nucleus, and in association with the centrosome of interphase cells. Here, we explore contributions of the LD to the assembly of supramolecular actin structures in real time by total internal reflection fluorescence (TIRF) microscopy. Our data shows that while LD on its own cannot polymerize under filament forming conditions, it is able to incorporate into growing F-actin filaments. This incorporation of LD triggers the formation of X-shaped filament assemblies with barbed ends that are pointing in the same direction in the majority of cases. Similarly, an increased frequency of junction sites was observed when filaments were assembled in the presence of oxidized actin. This data suggests that a disulfide bridge between Cys374 residues might stabilize LD-contacts. Based on our findings, we propose two possible models for the molecular mechanism underlying the supramolecular actin patterning in LD-related structures. PMID- 27189867 TI - A multilayer micromechanical model of the cuticle of Curculio longinasus Chittenden, 1927 (Coleoptera: Curculionidae). AB - Curculio longinasus Chittenden, 1927 (Coleoptera: Curculionidae), is a weevil species common throughout the southwestern United States that uses its rostrum - a very slender, curved, beak-like projection of the head - to excavate tunnels in plant organs (such as acorns) for egg laying (oviposition). Once the apical portion of the rostrum has been inserted into the preferred substrate for oviposition, the female begins rotating around the perimeter of the hole, elevating her head by extending the fore-legs, and rotating the head in place in a drilling motion. This action causes significant elastic deformation of the rostrum, which will bend until it becomes completely straight. To better understand the mechanical behavior of the cuticle as it undergoes deformation during the preparation of oviposition sites, we develop a comprehensive micro/macro model of the micromechanical structure and properties of the cuticle, spanning across all cuticular regions, and reliably mirroring the resultant macroscale properties of the cuticle. Our modeling approach relies on the use of multi-scale, hierarchical biomaterial representation, and employs various micromechanical schemata - e.g., Mori-Tanaka, effective field, and Maxwell - to calculate the homogenized properties of representative volume elements at each level in the hierarchy. We describe the configuration and behavior of this model in detail, and discuss the theoretical implications and limitations of this approach with emphasis on future biomechanical and comparative evolutionary research. Our detailed account of this approach can thereby serve as a methodological template for exploring the biomechanical behavior of new insect structures. PMID- 27189865 TI - Impact of Microbiome on Ocular Health. AB - The ocular surface is continuously exposed to the environment and, therefore, it is surprising that it harbors only few commensals with low degree of diversity. This unique aspect of the ocular surface physiology prompts the question whether there are core ocular commensal communities and how they affect ocular immunity. The purpose of this review is to provide an overview of what is known about the ocular surface commensals in health and disease and what we would like to learn in the near future. In addition, we discuss how microbiota at sites other than the eye may influence ocular immune responses. The information discussed in the review has been gathered using PubMed searches for literature published from January 1982 to December 2015. PMID- 27189868 TI - A Novel Strategy for Live Detection of Viral Infection in Drosophila melanogaster. AB - We have created a transgenic reporter for virus infection, and used it to study Nora virus infection in Drosophila melanogaster. The transgenic construct, Munin, expresses the yeast transcription factor Gal4, tethered to a transmembrane anchor via a linker that can be cleaved by a viral protease. In infected cells, liberated Gal4 will then transcribe any gene that is linked to a promoter with a UAS motif, the target for Gal4 transcription. For instance, infected cells will glow red in the offspring of a cross between the Munin stock and flies with a UAS RFP(nls) transgene (expressing a red fluorescent protein). In such flies we show that after natural infection, via the faecal-oral route, 5-15% of the midgut cells are infected, but there is little if any infection elsewhere. By contrast, we can detect infection in many other tissues after injection of virus into the body cavity. The same principle could be applied for other viruses and it could also be used to express or suppress any gene of interest in infected cells. PMID- 27189869 TI - [Ag20 {S2 P(OR)2 }12 ]: A Superatom Complex with a Chiral Metallic Core and High Potential for Isomerism. AB - The synthesis and structural determination of a silver nanocluster [Ag20 {S2 P(OiPr)2 }12 ] (2), which contains an intrinsic chiral metallic core, is produced by reduction of one silver ion from the eight-electron superatom complex [Ag21 {S2 P(OiPr)2 }12 ](PF6 ) (1) by borohydrides. Single-crystal X-ray analysis displays an Ag20 core of pseudo C3 symmetry comprising a silver-centered Ag13 icosahedron capped by seven silver atoms. Its n-propyl derivative, [Ag20 {S2 P(OnPr)2 }12 ] (3), can also be prepared by the treatment of silver(I) salts and dithiophosphates in a stoichiometric ratio in the presence of excess amount of [BH4 ](-) . Crystal structure analyses reveal that the capping silver-atom positions relative to their icosahedral core are distinctly different in 2 and 3 and generate isomeric, chiral Ag20 cores. Both Ag20 clusters display an emission maximum in the near IR region. DFT calculations are consistent with a description within the superatom model of an 8-electron [Ag13 ](5+) core protected by a [Ag7 {S2 P(OR)2 }12 ](5-) external shell. Two additional structural variations are predicted by DFT, showing the potential for isomerism in such [Ag20 {S2 P(OR)2 }12 ] species. PMID- 27189870 TI - The Influence of Knee Flexion Angle for Graft Fixation on Rotational Knee Stability During Anterior Cruciate Ligament Reconstruction: A Biomechanical Study. AB - PURPOSE: To evaluate the effect of knee flexion angle for hamstring graft fixation, full extension (FE), or 30 degrees , on acceleration of the knee motion during pivot-shift testing after either anatomic or nonanatomic anterior cruciate ligament (ACL) reconstruction using triaxial accelerometry. METHODS: Two types of ACL reconstructions (anatomic and nonanatomic) using 2 different angles of knee flexion during graft fixation (FE and 30 degrees ) were performed on 12 fresh frozen human knees making 4 groups: anatomic-FE, anatomic-30 degrees , nonanatomic-FE, and nonanatomic-30 degrees . Manual pivot-shift testing was performed at ACL-intact, ACL-deficient, and ACL-reconstructed conditions. Three dimensional acceleration of knee motion was recorded using a triaxial accelerometer. RESULTS: The anatomic-30 degrees group showed the smallest overall magnitude of acceleration among the ACL-reconstructed groups (P = .0039). There were no significant differences among the anatomic-FE group, the nonanatomic-FE group, and the nonantomic-30 degrees group (anatomic-FE vs nonanatomic-FE, P = .1093; anatomic-FE vs nonanatomic-30 degrees , P = .8728; and nonanatomic-FE vs nonanatomic-30 degrees , P = .1093). After ACL transection, acceleration was reduced by ACL reconstruction with the exception of the nonanatomic-FE group that did not show a significant difference when compared with the ACL-deficient (P = .4537). CONCLUSIONS: The anatomic ACL reconstruction with the graft fixed at 30 degrees of knee flexion better restored rotational knee stability compared with FE. An ACL graft fixed with the knee at FE in anatomic position did not show a significant difference compared with the nonanatomic ACL reconstructions. CLINICAL RELEVANCE: Knee flexion angle at the time of graft fixation for ACL reconstruction can be considered to maximize the rotational knee stability. PMID- 27189871 TI - Arthroscopic Management of Femoroacetabular Impingement in Adolescents. AB - PURPOSE: To report the outcomes of hip arthroscopy for adolescent patients with symptomatic femoroacetabular impingement (FAI) in relation to a control group of adult patients treated arthroscopically for FAI. METHODS: All patients undergoing hip arthroscopy were assessed with a modified Harris Hip Score preoperatively and postoperatively at 3, 12, 24, and 60 months. Inclusion criteria were all patients less than 18 years of age who underwent arthroscopic surgery for symptomatic FAI and had achieved minimum 1-year follow-up. These cases were gathered over an 8 year period. RESULTS: The study group consisted of 122 consecutive hips (108 patients), and the control group consisted of 122 hips. Follow-up averaged 30 months (range 12 to 60 months). For the study group, the average age was 16 years, with 55 males and 65 females; control group average age was 36 years, with 71 males and 51 females. In the study group, the average scores were preoperative 68.3 and postoperative 93.6, with a 25.4-point improvement. The duration of symptoms averaged 16.6 months, and 95.9% participated in athletic activities. The study group included 36 cam, 17 pincer, and 69 combined lesions. One hundred eleven labral tears underwent 85 refixations and 26 debridements; there were 101 acetabular chondral lesions (51 grade 3 or 4), with 4 microfractures and 3 femoral chondral lesions. Among the control group, the average scores were preoperative 63.3 and postoperative 85.5, with a 22.2-point improvement. The duration of symptoms averaged 31.2 months, and 61.5% participate in athletic activities. The control group consisted of 53 cam, 5 pincer, and 64 combined FAI lesions. One hundred three labral tears underwent 52 refixations and 51 debridements; there were 112 acetabular lesions (92 grade 3 or 4), with 20 microfractures and 17 femoral chondral lesions. The study group included 15 concomitant extra-articular procedures, and there were 5 in the control group. In the study group, 4 underwent repeat arthroscopy and 1 periacetabular osteotomy; in the control group, 1 patient underwent repeat arthroscopy. CONCLUSIONS: Favorable outcomes of arthroscopic management of FAI in adolescents are reported compared with an adult control group. The present data support that arthroscopy does have a role in the management of FAI in adolescents. LEVEL OF EVIDENCE: Level III, case control study. PMID- 27189872 TI - Acne vulgaris. AB - Acne vulgaris is a chronic inflammatory disease - rather than a natural part of the life cycle as colloquially viewed - of the pilosebaceous unit (comprising the hair follicle, hair shaft and sebaceous gland) and is among the most common dermatological conditions worldwide. Some of the key mechanisms involved in the development of acne include disturbed sebaceous gland activity associated with hyperseborrhoea (that is, increased sebum production) and alterations in sebum fatty acid composition, dysregulation of the hormone microenvironment, interaction with neuropeptides, follicular hyperkeratinization, induction of inflammation and dysfunction of the innate and adaptive immunity. Grading of acne involves lesion counting and photographic methods. However, there is a lack of consensus on the exact grading criteria, which hampers the conduction and comparison of randomized controlled clinical trials evaluating treatments. Prevention of acne relies on the successful management of modifiable risk factors, such as underlying systemic diseases and lifestyle factors. Several treatments are available, but guidelines suffer from a lack of data to make evidence-based recommendations. In addition, the complex combination treatment regimens required to target different aspects of acne pathophysiology lead to poor adherence, which undermines treatment success. Acne commonly causes scarring and reduces the quality of life of patients. New treatment options with a shift towards targeting the early processes involved in acne development instead of suppressing the effects of end products will enhance our ability to improve the outcomes for patients with acne. PMID- 27189874 TI - Features of successful academic hospitalist programs: Insights from the SCHOLAR (SuCcessful HOspitaLists in academics and research) project. AB - BACKGROUND: As clinical demands increase, understanding the features that allow academic hospital medicine programs (AHPs) to thrive has become increasingly important. OBJECTIVE: To develop and validate a quantifiable definition of academic success for AHPs. METHODS: A working group of academic hospitalists was formed. The group identified grant funding, academic promotion, and scholarship as key domains reflective of success, and specific metrics and approaches to assess these domains were developed. Self-reported data on funding and promotion were available from a preexisting survey of AHP leaders, including total funding/group, funding/full-time equivalent (FTE), and number of faculty at each academic rank. Scholarship was defined in terms of research abstracts presented over a 2-year period. Lists of top performers in each of the 3 domains were constructed. Programs appearing on at least 1 list (the SCHOLAR cohort [SuCcessful HOspitaLists in Academics and Research]) were examined. We compared grant funding and proportion of promoted faculty within the SCHOLAR cohort to a sample of other AHPs identified in the preexisting survey. RESULTS: Seventeen SCHOLAR programs were identified, with a mean age of 13.2 years (range, 6-18 years) and mean size of 36 faculty (range, 18-95). The mean total grant funding/program was $4 million (range, $0-$15 million), with mean funding/FTE of $364,000 (range, $0-$1.4 million); both were significantly higher than the comparison sample. The majority of SCHOLAR faculty (82%) were junior, a lower percentage than the comparison sample. The mean number of research abstracts presented over 2 years was 10.8 (range, 9-23). DISCUSSION: Our approach effectively identified a subset of successful AHPs. Despite the relative maturity and large size of the programs in the SCHOLAR cohort, they were comprised of relatively few senior faculty members and varied widely in the quantity of funded research and scholarship. Journal of Hospital Medicine 2016;11:708-713. (c) 2016 Society of Hospital Medicine. PMID- 27189875 TI - Characteristics of Effective Disaster Responders and Leaders: A Survey of Disaster Medical Practitioners. AB - OBJECTIVE: To identify key attributes of effective disaster/mass casualty first responders and leaders, thereby informing the ongoing development of a capable disaster health workforce. METHODS: We surveyed emergency response practitioners attending a conference session, the EMS State of the Science: A Gathering of Eagles. We used open-ended questions to ask participants to describe key characteristics of successful disaster/mass casualty first responders and leaders. RESULTS: Of the 140 session attendees, 132 (94%) participated in the survey. All responses were categorized by using a previously developed framework. The most frequently mentioned characteristics were related to incident command/disaster knowledge, teamwork/interpersonal skills, performing one's role, and cognitive abilities. Other identified characteristics were related to communication skills, adaptability/flexibility, problem solving/decision-making, staying calm and cool under stress, personal character, and overall knowledge. CONCLUSIONS: The survey findings support our prior focus group conclusion that important characteristics of disaster responders and leaders are not limited to the knowledge and skills typically included in disaster training. Further research should examine the extent to which these characteristics are consistently associated with actual effective performance of disaster response personnel and determine how best to incorporate these attributes into competency models, processes, and tools for the development of an effective disaster response workforce. (Disaster Med Public Health Preparedness. 2016;page 1 of 4). PMID- 27189877 TI - Nitrous oxide emissions from an aerobic granular sludge system treating low strength ammonium wastewater. AB - Aerobic granular sludge is a promising technology in wastewater treatment process. Its special microorganism structure could make the emissions of greenhouse gas nitrous oxide (N2O) more complicated. This study investigated the N2O emissions from a batch-fed aerobic granular sludge system during nitrification of low-strength synthetic ammonium wastewater. The N2O emission was 2.72 +/- 0.52% of the oxidized ammonium during the whole anoxic-oxic sequencing batch reactor (SBR) cycle. Under nitrification batch test with sole ammonium substrate (50 mg N/L), N2O emission factor was 1.82% (N2ON/NH4+-Nox) and ammonia oxidizing bacteria (AOB) was the responsible microorganism. The presence of high ammonium concentration (or high ammonium oxidation rate (AOR)) and accumulation of nitrite would lead to significant N2O emissions. AOB denitrification pathway was speculated to contribute more to the N2O emissions under nitrification conditions. While under simultaneous nitrification and denitrification condition with carbon source of 500 mg COD/L, the N2O emission factor increased to 2.76%. Both AOB and heterotrophic denitrifiers were responsible for N2O emission and heterotrophic denitrification enhances N2O emission. Step feeding of organic carbon source declined N2O emission factor to 1.60%, which underlined the role of storage substance consumption in N2O generation during denitrification. PMID- 27189878 TI - Sequential Nanopatterned Block Copolymer Self-Assembly on Surfaces. AB - Bottom-up self-assembly of high-density block-copolymer nanopatterns is of significant interest for a range of technologies, including memory storage and low-cost lithography for on-chip applications. The intrinsic or native spacing of a given block copolymer is dependent upon its size (N, degree of polymerization), composition, and the conditions of self-assembly. Polystyrene-block polydimethylsiloxane (PS-b-PDMS) block copolymers, which are well-established for the production of strongly segregated single-layer hexagonal nanopatterns of silica dots, can be layered sequentially to produce density-doubled and -tripled nanopatterns. The center-to-center spacing and diameter of the resulting silica dots are critical with respect to the resulting double- and triple-layer assemblies because dot overlap reduces the quality of the resulting pattern. The addition of polystyrene (PS) homopolymer to PS-b-PDMS reduces the size of the resulting silica dots but leads to increased disorder at higher concentrations. The quality of these density-multiplied patterns can be calculated and predicted using parameters easily derived from SEM micrographs of corresponding single and multilayer patterns; simple geometric considerations underlie the degree of overlap of dots and layer-to-layer registration, two important factors for regular ordered patterns, and clearly defined dot borders. Because the higher molecular-weight block copolymers tend to yield more regular patterns than smaller block copolymers, as defined by order and dot circularity, this sequential patterning approach may provide a route toward harnessing these materials, thus surpassing their native feature density. PMID- 27189876 TI - Inhibition of Endocannabinoid Degradation Improves Outcomes from Mild Traumatic Brain Injury: A Mechanistic Role for Synaptic Hyperexcitability. AB - Traumatic brain injury (TBI) is an increasingly prevalent condition affecting soldiers, athletes, and motor vehicle accident victims. Unfortunately, it currently lacks effective therapeutic interventions. TBI is defined as a primary mechanical insult followed by a secondary cascade involving inflammation, apoptosis, release of reactive oxygen species, and excitotoxicity, all of which can cause synaptic changes, altered neuronal signaling, and, ultimately, behavioral changes. Previously we showed that preventing degradation of the endocannabinoid (EC) 2-acylglycerol (2-AG) with JZL184 after mild TBI attenuated neuroinflammation and improved recovery of neurobehavioral function during the early 24 h post-TBI period. The aim of this study was to extend the timeline of observations to 2 weeks post-injury and to investigate JZL184's impact on synaptic transmission, which we view as a potential mechanism for TBI-induced cellular and behavioral pathology. Adult male rats underwent mild TBI (mTBI) followed by a single intraperitoneal injection of JZL184 or vehicle 30 min post injury. JZL184 administered-TBI animals showed improved neurobehavioral recovery compared with vehicle-injected TBI animals beginning 24 h post-injury and persisting for 2 weeks. JZL184-treated animals had significantly diminished gray and white matter astrocyte activation when compared with vehicle-treated animals at day 7 post-TBI. JZL184 administration significantly attenuated the increased pGluR1S845/GluR1 and pERK 1/2/ERK and the increases in miniature excitatory postsynaptic potential (mEPSC) frequency and amplitude observed in layer 5 pyramidal neurons at 10 days post-TBI. These results suggest a neuroprotective role for ECs in ameliorating the TBI-induced neurobehavioral, neuroinflammatory, and glutamate dyshomeostasis from mTBI. Further studies elucidating the cellular mechanisms involved are warranted. PMID- 27189879 TI - Liver fibrosis progression predicts survival in patients with primary biliary cirrhosis. PMID- 27189880 TI - Exploring the impact of parental post-traumatic stress disorder on military family children: A review of the literature. AB - OBJECTIVES: The number of UK service personnel who have a diagnosis of PTSD is unclear, but there has been a recent increase in referrals to services for PTSD symptomology. It is imperative to understand the impact this may have on the children of affected service families. This review of literature aimed to explore and provide insight into the experiences of services children whose parent has a diagnosis of PTSD. DESIGN: A comprehensive review of the literature. DATA SOURCES: Online databases CINAHL, MEDLINE, psychARTICLES, The Psychology and Behavioural Sciences Collection and PILOTS were searched. REVIEW METHODS: The studies were chosen in keeping with a specified inclusion and exclusion criteria. The literature was critically analysed and key themes identified through the strategy of thematic analysis. RESULTS: Five studies met the inclusion criteria. Three key themes were identified from the five articles; secondary traumatisation; impact on the child's mental health; and impact on the child's adult relationships. CONCLUSION: The findings highlighted the prevalence of secondary traumatisation and a potential negative impact on the child's mental health and relationships. However, literature used in the review was conducted in countries outside of the UK, therefore the comparison of results may be compromised. This review identifies the paucity of research on this topic and highlights the need for UK based research to be carried out in this area. PMID- 27189883 TI - Neuregulin 1-ErbB4 signaling in the bed nucleus of the stria terminalis regulates anxiety-like behavior. AB - The bed nucleus of the stria terminalis (BNST), a nucleus defined as part of the extended amygdala, is involved in the expression of anxiety disorders. However, the regulatory mechanisms of BNST inhibitory activity that is involved in anxiety are unknown. Here, we showed that blocking neuregulin 1 (NRG1)-ErbB4 signaling in the BNST of mice, by either neutralizing endogenous NRG1 with ecto-Erbb4 or antagonizing the ErbB4 receptor with its specific inhibitor, produced anxiogenic responses. Interestingly, application of exogenous NRG1 into the BNST induced no anxiolytic effects, suggesting saturating activity of endogenous NRG1. While infusion of the GABAA receptor antagonist bicuculline into the BNST also led to anxiety-related behaviors, it did not worsen the anxiogenic effects produced by blocking NRG1-ErbB4 signaling, suggesting possible involvement of GABAergic neurotransmission. Further, in vitro electrophysiological recordings showed that BNST NRG1-ErbB4 signaling regulated the presynaptic GABA release. Together, these results suggest that NRG1-ErbB4 signaling in the BNST may play an important role in regulating anxiety-like behaviors. PMID- 27189884 TI - Decline of microtubule-associated protein tau after experimental stroke in differently aged wild-type and 3xTg mice with Alzheimer-like alterations. AB - Stroke therapies are still limited to a minority of patients. Considering time dependent aspects of stroke, the penumbra concept describes the transition from functional to permanent tissue damage. Thereby, the role of cytoskeletal elements, as for instance microtubules with associated tau remains poorly understood and is therefore not yet considered for therapeutic approaches. This study explored the expression of microtubule-associated protein tau related to neuronal damage in stroke-affected brain regions. Wild-type and triple-transgenic mice of 3, 7 and 12months of age and with an Alzheimer-like background underwent experimental stroke. After 24h, brain sections were used for immunofluorescence labeling of tau and Neuronal Nuclei (NeuN). Potential functional consequences of cellular alterations were explored by statistical relationships to the general health condition, i.e. neurobehavioral deficits and loss of body weight. Immunoreactivity for whole tau decreased significantly in ischemic areas, while the decline at the border zone was more drastic for tau-immunoreactivity compared with the diminished NeuN labeling. Quantitative analyses confirmed pronounced sensitivity for tau-immunoreactivity in the ischemic border zone. Decline of tau- as well as NeuN-immunoreactivity correlated with body weight loss during the 24-h observation period. In conclusion, microtubule-associated protein tau was robustly identified as a highly sensitive cytoskeletal constitute under ischemic conditions, suggesting a pivotal role during the transition process toward long lasting tissue damage. Consequently, cytoskeletal elements appear as promising targets for novel therapeutic approaches with the objective to impede ischemia induced irreversible cellular degradation. PMID- 27189881 TI - Modulation of pain, nociception, and analgesia by the brain reward center. AB - The midbrain dopamine center comprises a key network for reward, salience, motivation, and mood. Evidence from various clinical and preclinical settings points to the midbrain dopamine circuit as an important modulator of pain perception and pain-induced anxiety and depression. This review summarizes recent findings that shed light to the neuroanatomical, electrophysiological and molecular adaptations that chronic pain conditions promote in the mesolimbic dopamine system. Chronic pain states induce changes in neuronal plasticity and functional connectivity in several parts of the brain reward center, including nucleus accumbens, the ventral tegmental area and the prefrontal cortex. Here, we discuss recent findings on the mechanisms involved in the perception of chronic pain, in pain-induced anxiety and depression, as well as in pain-killer addiction vulnerability. Several new studies also show that the mesolimbic dopamine circuit potently modulates responsiveness to opioids and antidepressants used for the treatment of chronic pain. We discuss recent data supporting a role of the brain reward pathway in treatment efficacy and we summarize novel findings on intracellular adaptations in the brain reward circuit under chronic pain states. PMID- 27189882 TI - Touchscreen learning deficits and normal social approach behavior in the Shank3B model of Phelan-McDermid Syndrome and autism. AB - SHANK3 is a synaptic scaffolding protein localized in the postsynaptic density and has a crucial role in synaptogenesis and neural physiology. Deletions and point mutations in SHANK3 cause Phelan-McDermid Syndrome (PMS), and have also been implicated in autism spectrum disorder (ASD) and intellectual disabilities, leading to the hypothesis that reduced SHANK3 expression impairs basic brain functions that are important for social communication and cognition. Several mouse models of Shank3 deletions have been generated, varying in the specific domain deleted. Here we report impairments in cognitive function in mice heterozygous for exon 13-16 (coding for the PDZ domain) deletion. The touchscreen pairwise discrimination task was chosen by virtue of its: (a) conceptual and technical similarities to the Cambridge Neuropsychological Test Automated Battery (CANTAB) and NIH Toolbox Cognition Battery used for testing cognitive functions in humans, (b) minimal demand on motor abilities, and (c) capability to measure many aspects of learning and memory and complex cognitive functions, including cognitive flexibility. The similarity between our mouse tasks and human cognitive assays means a high translational validity in future intervention studies using preclinical models. Our study revealed that Shank3B heterozygous mice (+/-) were slower to reach criterion in the pairwise visual discrimination task, and exhibited trends toward making more errors (first trial errors) and more correction errors than wildtype mice (+/+). Open field activity was normal in +/ , ruling out hypo- or hyperactivity as potential confounds in the touchscreen test. Sociability in the three chamber test was also normal in both +/+ and +/-. These results indicate a deficit in discrimination learning in the Shank3B model of PMS and ASD, suggesting that this mouse model is a useful preclinical tool for studying neurobiological mechanisms behind cognitive impairments in PMS and ASD. The current findings are the starting point for our future research in which we will investigate multiple domains of cognition and explore pharmacological interventions. PMID- 27189885 TI - Sarcolemmal Ca(2+)-entry through L-type Ca(2+) channels controls the profile of Ca(2+)-activated Cl(-) current in canine ventricular myocytes. AB - Ca(2+)-activated Cl(-) current (ICl(Ca)) mediated by TMEM16A and/or Bestrophin-3 may contribute to cardiac arrhythmias. The true profile of ICl(Ca) during an actual ventricular action potential (AP), however, is poorly understood. We aimed to study the profile of ICl(Ca) systematically under physiological conditions (normal Ca(2+) cycling and AP voltage-clamp) as well as in conditions designed to change [Ca(2+)]i. The expression of TMEM16A and/or Bestrophin-3 in canine and human left ventricular myocytes was examined. The possible spatial distribution of these proteins and their co-localization with Cav1.2 was also studied. The profile of ICl(Ca), identified as a 9-anthracene carboxylic acid-sensitive current under AP voltage-clamp conditions, contained an early fast outward and a late inward component, overlapping early and terminal repolarizations, respectively. Both components were moderately reduced by ryanodine, while fully abolished by BAPTA, but not EGTA. [Ca(2+)]i was monitored using Fura-2-AM. Setting [Ca(2+)]i to the systolic level measured in the bulk cytoplasm (1.1MUM) decreased ICl(Ca), while application of Bay K8644, isoproterenol, and faster stimulation rates increased the amplitude of ICl(Ca). Ca(2+)-entry through L-type Ca(2+) channels was essential for activation of ICl(Ca). TMEM16A and Bestrophin-3 showed strong co-localization with one another and also with Cav1.2 channels, when assessed using immunolabeling and confocal microscopy in both canine myocytes and human ventricular myocardium. Activation of ICl(Ca) in canine ventricular cells requires Ca(2+)-entry through neighboring L-type Ca(2+) channels and is only augmented by SR Ca(2+)-release. Substantial activation of ICl(Ca) requires high Ca(2+) concentration in the dyadic clefts which can be effectively buffered by BAPTA, but not EGTA. PMID- 27189887 TI - Stable and biocompatible cystine knot peptides from the marine sponge Asteropus sp. AB - Two new cystine knot peptides, asteropsins F (ASPF) and G (ASPG), were isolated from the marine sponge Asteropus sp. ASPF and ASPG are composed of 33 and 32 amino acids, respectively, and contain six cysteines which are involved in three disulfide bonds. They shared the characteristic features of the asteropsin family, such as, N-terminal pyroglutamate modification, incorporation of cis prolines, and the unique anionic profile, which distinguish them from other knottin families. Tertiary structures of the peptides were determined by high resolution NMR. ASPF and ASPG were found to be remarkably resistant not only to digestive enzymes (chymotrypsin, pepsin, elastase, and trypsin) but also to thermal degradation. In addition, these peptides were pharmacologically inert; non-hemolytic to human and fish red blood cells, non-stimulatory to murine macrophage cells, and nontoxic in vitro or in vivo. These observations support their stability and biocompatibility as suitable carrier scaffolds for the design of oral peptide drug. PMID- 27189888 TI - Optimization of the phenylurea moiety in a phosphoinositide 3-kinase (PI3K) inhibitor to improve water solubility and the PK profile by introducing a solubilizing group and ortho substituents. AB - Phosphoinositide 3-kinase (PI3K) is a promising anti-cancer target, because various mutations and amplifications are observed in human tumors isolated from cancer patients. Our dihydropyrrolopyrimidine derivative with a phenylurea moiety showed strong PI3K enzyme inhibitory activity, but its pharmacokinetic property was poor because of lack of solubility. Herein, we report how we improved the solubility of our PI3K inhibitors by introducing a solubilizing group and ortho substituents to break molecular planarity. PMID- 27189886 TI - Recent advances in the discovery and development of antibacterial agents targeting the cell-division protein FtsZ. AB - With the emergence of multidrug-resistant bacterial strains, there is a dire need for new drug targets for antibacterial drug discovery and development. Filamentous temperature sensitive protein Z (FtsZ), is a GTP-dependent prokaryotic cell division protein, sharing less than 10% sequence identity with the eukaryotic cell division protein, tubulin. FtsZ forms a dynamic Z-ring in the middle of the cell, leading to septation and subsequent cell division. Inhibition of the Z-ring blocks cell division, thus making FtsZ a highly attractive target. Various groups have been working on natural products and synthetic small molecules as inhibitors of FtsZ. This review summarizes the recent advances in the development of FtsZ inhibitors, focusing on those in the last 5years, but also includes significant findings in previous years. PMID- 27189889 TI - Individually customisable non-invasive head immobilisation system for non-human primates with an option for voluntary engagement. AB - BACKGROUND: Head immobilisation is often necessary for neuroscientific procedures. A number of Non-invasive Head Immobilisation Systems (NHIS) for monkeys are available, but the need remains for a feasible integrated system combining a broad range of essential features. NEW METHOD: We developed an individualised macaque NHIS addressing several animal welfare and scientific needs. The system comprises a customised-to-fit facemask that can be used separately or combined with a back piece to form a full-head helmet. The system permits presentation of visual and auditory stimuli during immobilisation and provides mouth access for reward. RESULTS: The facemask was incorporated into an automated voluntary training system, allowing the animals to engage with it for increasing periods leading to full head immobilisation. We evaluated the system during performance on several auditory or visual behavioural tasks with testing sessions lasting 1.5-2h, used thermal imaging to monitor for and prevent pressure points, and measured head movement using MRI. COMPARISON WITH EXISTING METHODS: A comprehensive evaluation of the system is provided in relation to several scientific and animal welfare requirements. Behavioural results were often comparable to those obtained with surgical implants. Cost-benefit analyses were conducted comparing the system with surgical options, highlighting the benefits of implementing the non-invasive option. CONCLUSIONS: The system has a number of potential applications and could be an important tool in neuroscientific research, when direct access to the brain for neuronal recordings is not required, offering the opportunity to conduct non-invasive experiments while improving animal welfare and reducing reliance on surgically implanted head posts. PMID- 27189891 TI - Relationship between pulmonary arterial resistance and compliance among patients with pulmonary arterial hypertension and congenital heart disease. AB - BACKGROUND: It is unknown whether changes in pulmonary arterial resistance (Rp), pulmonary arterial compliance (Cp), and the product of Rp and Cp (the RC time) in patients with pulmonary arterial hypertension (PAH) are related to an increase in pulmonary blood flow. The aim of this study is to clarify relationships between these parameters before and after corrective surgery among patients with PAH and congenital heart disease. METHODS: We performed cardiac catheter examinations and compared Rp, Cp, and the RC time before and after corrective surgery in 100 infants (53 boys) with PAH related to ventricular septal defect. RESULTS: Median age at surgery was 2.9 (0.6-28.5) months. Preoperative values of the ratio of pulmonary to systemic blood flow (Qp/Qs), systolic pulmonary arterial pressure (PAP), Rp, Cp, and the RC time were 3.5 (2.7-4.3), 65 (56-70) mm Hg, 2.18 (1.64 3.19) Wood unit/m(2), 2.67 (2.01-3.38) mL/mm Hg/m(2), and 0.36 (0.31-0.40) seconds, respectively. Postoperative systolic PAP, Cp, and the RC time were significantly decreased to 26 (23-29) mm Hg, 1.96 (1.77-2.26) mL/mm Hg/m(2), and 0.31 (0.26-0.36) seconds, respectively, although Rp remained unchanged at 2.53 (2.06-3.31) Wood unit/m(2). The relationship between Rp and Cp was inversely related before and after surgery, and the Rp-Cp coupling curve was shifted downward after surgery. In addition, lower preoperative Cp (partial regression coefficient = -3.35; P = .001) and preterm delivery (partial regression coefficient = 6.28; P = .02) were independently related to postoperative higher systolic PAP. CONCLUSIONS: Rp-Cp coupling depends on both the amount of pulmonary blood flow and the condition of the pulmonary vasculature. Lower preoperative Cp is an independent predictive factor to predict higher postoperative pulmonary systolic pressure leading to an increase in right ventricular workload. It is necessary to assess Rp-Cp coupling before surgery among patients with PAH related to congenital heart disease. PMID- 27189890 TI - Computed tomography-guided patent blue vital dye localization of pulmonary nodules in uniportal thoracoscopy. AB - OBJECTIVE: Due to the limitations of the small single incision, an ideal preoperative localization technique is essential for surgical resection of small pulmonary nodules by uniportal video-assisted thoracoscopic surgery (VATS). The aim of this study is to evaluate the usefulness and safety of preoperative computed tomography (CT)-guided patent blue vital (PBV) dye localization in patients with small indeterminate pulmonary nodules who have undergone uniportal VATS for lung resection. METHODS: In this retrospective study, 177 consecutive patients (196 pulmonary nodules) who underwent preoperative CT-guided PBV dye localization and uniportal VATS from January 2013 to September 2015 were enrolled. RESULTS: The CT-dye localization procedure was performed successfully and correctly for 99.5% (195/196) of the nodules within a mean procedure time of 30 minutes. The mean size of the nodules was 7.8 mm, and their mean depth from the pleural surface was 18.3 mm. Most of the nodules (78.6%, 154/196) were pure ground-glass nodules (GGNs) and part-solid GGN with ground-glass opacity (GGO) of 50% or more. Asymptomatic pneumothorax occurred in 29.4% (52/177) of patients after the localization procedure, but none required invasive treatment. All nodules were successfully resected using uniportal VATS without any conversion to thoracotomy. The postoperative course was smooth, with a short mean hospital stay (3.3 +/- 1.2 days) and a low morbidity rate (0.6%, 1/177). CONCLUSIONS: Preoperative CT-guided PBV dye localization is a feasible, safe, and accurate procedure. It makes uniportal VATS easy for small, poorly located pulmonary nodules with GGO predominance and synchronous multiple nodules. PMID- 27189892 TI - American College of Cardiology/American Heart Association 2016 dual antiplatelet therapy (DAPT) focused update: Implications for surgeons. PMID- 27189893 TI - Circular shunt in bidirectional cavopulmonary anastomosis. PMID- 27189895 TI - Erratum to "Neurosensory Recovery of the Infra-Orbital Nerve Following Maxillary Orthognathic Surgery" [2015; vol 120, No. 5, p e202]. PMID- 27189894 TI - Probability of fallopian tube and ovarian detection with transvaginal ultrasonography in normal women. AB - OBJECTIVE: Some ovarian malignancies may originate in the fallopian tube. The feasibility of ultrasonographically visualizing the fallopian tube is presented. METHODS: In total, 549 normal women participated in the fallopian tube visualization trial, while ovarian visualization was studied in 43,521. Chi square analysis, t-tests and multivariate analysis determined significance and interactions. RESULTS: Ovaries were observed in 82.7% while fallopian tubes were detected in 77.2% of women and 85.2% of the time when an ovary was detected. Age, BMI or parity was not significantly different when one or both fallopian tubes were visualized. Elevated BMI had slightly greater influence than age in limiting visualization of the fallopian tubes in multivariate analysis. CONCLUSION: Fallopian tubes can often be identified sonographically. Ovarian visualization provides the strongest indicator favoring fallopian tube detection. Thus, ultrasonographic examinations for adnexal cancer could include evaluation of fallopian tubes even in women >60 years and in women with BMI >=25. PMID- 27189896 TI - Xerostomia: current streams of investigation. AB - Xerostomia is the subjective feeling of dry mouth, and it is often related to salivary hypofunction. Besides medication-related salivary hypofunction, Sjogren syndrome and head-and-neck radiation are two common etiologies that have garnered considerable attention. Approaches to treating and/or preventing salivary hypofunction in patients with these conditions will likely incorporate gene therapy, stem cell therapy, and tissue engineering. Advances in these disciplines are central to current research in the cure for xerostomia and will be key to eventual treatment. PMID- 27189897 TI - Prospectively-collected, tooth-specific dosimetry correlated with adverse dental outcomes. AB - OBJECTIVES: To correlate radiation dose to specific tooth-bearing portions of bone with adverse dental outcomes. STUDY DESIGN: Eighty-nine patients treated with intensity-modulated radiation therapy with or without chemotherapy had radiation dose to specific tooth-bearing portions of the mandible and the maxilla. Data were collected prospectively during treatment planning, which resulted in 2490 data points. These patients underwent a comprehensive dental intake evaluation that included measurement of pocket depths and were then followed up with serial dental evaluations for a median of 2.5 years (range 0.2 6.9 years). RESULTS: At the patient level, the 3-year risks of osteoradionecrosis (ORN) and periodontal disease were 2.5% and 36.6%, respectively. For any individual tooth, the risks of ORN and periodontal disease were 0.1% and 5.1%, respectively, at 3 years. Radiation dose to individual tooth-bearing portions of bone was correlated with ORN development (P = .0165). Periodontal disease also demonstrated a significant, but more gradual, dose response (P = .0395). CONCLUSIONS: Adverse dental outcomes directly correlate with increased tooth specific doses. PMID- 27189898 TI - Relabelling behaviour. The effects of psycho-education on the perceived severity and causes of challenging behaviour in people with profound intellectual and multiple disabilities. AB - BACKGROUND: Prevalence rates of challenging behaviour are high in children and adults with profound intellectual and multiple disabilities (PIMD). Moreover, many of these behaviours are observed daily. Direct support staff report that most challenging behaviour identified has little impact on the person with PIMD and attribute challenging behaviour in children and adults with PIMD mainly to a biomedical model. The purpose of this study was to evaluate whether an intervention (psycho-education) had any effect on direct support staff's assessment of challenging behaviour in terms of its severity and their biomedical causal explanations (attributions) for this behaviour. METHOD: A stepped wedge study design was used to evaluate the effects of a psycho-education intervention on the perceived severity and the attributions offered for challenging behaviour of people with PIMD by 198 direct support staff. We used questionnaires assessing the perceived severity of challenging behaviour and staff views of its causes. Data on the dependent variables were collected at four 1-month intervals. RESULTS: The intervention was found to have an effect on the perceived severity of challenging behaviour identified in people with PIMD in the sense that staff generally scored challenging behaviour as more severe in its consequences after the intervention. However, this effect was very small. No significant effects were found in terms of reduction in the biomedical scale scores. CONCLUSION: No evidence for the effectiveness of a psycho-educational approach on the assessment of challenging behaviour in terms of severity and the biomedical attributions for behaviour was found. More research is required to explore further the effects of more elaborate training using methods to enable direct support staff to reflect on the behaviour of people with PIMD and on their own behaviour. PMID- 27189899 TI - A randomized controlled trial of an educational programme with telephone reinforcement to improve perceived health status of Brazilian burn victims at 6 month post discharge. AB - AIM: The aim of this study was to compare health status, self-efficacy, symptoms of depression and anxiety and post-traumatic stress between two groups of burn victims receiving information on self-care through routine care or an educational programme with telephone reinforcement. BACKGROUND: Self-care post discharge is an important factor on quality of life of burn victims. Reinforcement of self care programme via telephone follow-up might improve self-efficacy and general health perception in burn victims. DESIGN: Randomized, controlled clinical trial. METHOD: From 2011-2012, we randomized 108 burn victims either to an educational programme on self-care tailored for burn victims according to the cognitive social theory and reinforcement by telephone every 4-6 weeks for 6 months post discharge, or to the routine instructions given at discharge from the hospital. During hospitalization, at discharge, at 6 and 12 months post discharge, we collected data on socio-demographic characteristics, Burns Specific Health Scale Revised (BSHS-R), Perceived Self-Efficacy Scale (PSE), Hospital Anxiety and Depression Scales (HADS) and Impact of the Event Scale (IES). We analysed data using t-test, Chi-square test and linear regression models. RESULTS: Groups were similar regarding clinical and demographic characteristics, except for age. At 6 month follow-up, there were no differences between the groups on BSHS-R, PSE and HADS Depression, while the intervention group showed fewer symptoms of anxiety (HADS Anxiety) and lower IES scores than the control group. CONCLUSION: The educational programme, when compared with usual care, reduced anxiety symptoms and post-traumatic stress. Educational programmes with telephone follow-up might be a viable intervention to improve self-care for burn victims. PMID- 27189900 TI - Liver-related mortality in countries of the developed world: an ecological study approach to explain the variability. AB - BACKGROUND: Liver-related mortality varies across developed nations. AIM: To assess the relative role of various risk factors in relation to liver-related mortality in an ecological study approach. METHODS: Data for liver-related mortality, prevalence data for hepatitis B and C, human immunodeficiency virus (HIV), alcohol consumption per capita, Type 2 Diabetes mellitus (T2DM), overweight and obesity were extracted from peer-reviewed publications or WHO databases for different developed countries. As potential other risk-modifying factors, purchase power parity (PPP)-adjusted gross domestic product (GDP) per capita and health expenditure per capita were assessed. As an environmental 'hygiene factor', we also assessed the effect of the prevalence of Helicobacter pylori. Only countries with a PPP-adjusted GDP greater than $20 000 and valid information for at least 8 risk modifiers were included. Univariate and multivariate analyses were utilised to quantify the contribution to the variability in liver-related mortality. RESULTS: The proportion of chronic liver diseases (CLD)-related mortality ranged from 0.73-2.40% [mean 1.56%, 95% CI (1.43 1.69)] of all deaths. Univariately, CLD-related mortality was significantly associated with Hepatitis B prevalence, alcohol consumption, PPP-adjusted GDP (all P < 0.05) and potentially H. pylori prevalence (P = 0.055). Other investigated factors, including hepatitis C, did not yield significance. Backward elimination suggested hepatitis B, alcohol consumption and PPP-adjusted GDP as risk factors (explaining 66.3% of the variability). CONCLUSION: Hepatitis B infection, alcohol consumption and GDP, but not hepatitis C or other factors, explain most of the variance of liver-related mortality. PMID- 27189901 TI - "Time Out": A Strategy for Reducing Men's Violence Against Women in Relationships? AB - This article critically explores accounts of how men attending domestic violence perpetrator programs (DVPP) used the "time out" strategy. Findings are drawn from 71 semi-structured interviews with 44 men attending DVPPs and 27 female partners or ex-partners of men in DVPPs. We describe three ways in which the technique was used: first, as intended, to interrupt potential physical violence; second, through the effective adaption of the time-out rules by victim-survivors; and finally, misappropriation by some men to continue and extend their controlling behaviors. Policy and practice lessons are drawn from the findings through connecting broader and deeper measurements of what success means when working with domestic violence perpetrators to the ways in which the time-out technique was used. PMID- 27189903 TI - Cortical spreading depolarization increases adult neurogenesis, and alters behavior and hippocampus-dependent memory in mice. AB - Cortical spreading depolarizations are an epiphenomenon of human brain pathologies and associated with extensive but transient changes in ion homeostasis, metabolism, and blood flow. Previously, we have shown that cortical spreading depolarization have long-lasting consequences on the brains transcriptome and structure. In particular, we found that cortical spreading depolarization stimulate hippocampal cell proliferation resulting in a sustained increase in adult neurogenesis. Since the hippocampus is responsible for explicit memory and adult-born dentate granule neurons contribute to this function, cortical spreading depolarization might influence hippocampus-dependent cognition. To address this question, we induced cortical spreading depolarization in C57Bl/6 J mice by epidural application of 1.5 mol/L KCl and evaluated neurogenesis and behavior at two, four, or six weeks thereafter. Congruent with our previous findings in rats, we found that cortical spreading depolarization increases numbers of newborn dentate granule neurons. Moreover, exploratory behavior and object location memory were consistently enhanced. Reference memory in the water maze was virtually unaffected, whereas memory formation in the Barnes maze was impaired with a delay of two weeks and facilitated after four weeks. These data show that cortical spreading depolarization produces lasting changes in psychomotor behavior and complex, delay- and task-dependent changes in spatial memory, and suggest that cortical spreading depolarization-like events affect the emotional and cognitive outcomes of associated brain pathologies. PMID- 27189902 TI - Advancing age and ischemia elevate the electric threshold to elicit spreading depolarization in the cerebral cortex of young adult rats. AB - Spreading depolarizations of long cumulative duration have been implicated in lesion development and progression in patients with stroke and traumatic brain injury. Spreading depolarizations evolve less likely in the aged brain, but it remains to be determined at what age the susceptibility to spreading depolarizations starts to decline, especially in ischemia. Spreading depolarizations were triggered by epidural electric stimulation prior and after ischemia induction in the cortex of 7-30 weeks old anesthetized rats ( n = 38). Cerebral ischemia was achieved by occlusion of both common carotid arteries. Spreading depolarization occurrence was confirmed by the acquisition of DC potential and electrocorticogram. Cerebral blood flow variations were recorded by laser-Doppler flowmetry. Dendritic spine density in the cortex was determined in Golgi-COX stained sections. Spreading depolarization initiation required increasingly greater electric charge with older age, a potential outcome of consolidation of cortical connections, indicated by altered dendritic spine distribution. The threshold of spreading depolarization elicitation increased with ischemia in all age groups, which may be caused by tissue acidosis and increased K+ conductance, among other factors. In conclusion, the brain appears to be the most susceptible to spreading depolarizations at adolescent age; therefore, spreading depolarizations may occur in young patients of ischemic or traumatic brain injury at the highest probability. PMID- 27189905 TI - New silent and weak D alleles: molecular characterization and associated antigen density. PMID- 27189904 TI - Risk of long-term anticoagulation under sustained severe arterial hypertension: A translational study comparing warfarin and the new oral anticoagulant apixaban. AB - New oral anticoagulants for the prevention of stroke and systemic embolism in patients with atrial fibrillation have recently been introduced. In this translational study, we explored the risk of long-term anticoagulation on intracerebral hemorrhage under sustained severe arterial hypertension. We initiated anticoagulation with warfarin or apixaban in spontaneously hypertensive rats prone to develop severe hypertension and subsequent intracerebral bleeding complications. A non-anticoagulated group served as control. During an 11-week study period, blood pressure, anticoagulation parameters, and clinical status were determined regularly. The incidence of histopathologically proven intracerebral hemorrhage was defined as the primary endpoint. Both warfarin and apixaban anticoagulation was fairly stable during the study period, and all rats developed severe hypertension. Intracerebral hemorrhage was determined in 29% (4/14) of warfarin rats and in 10% (1/10) of apixaban rats. Controls did not show cerebral bleeding complications (chi-square not significant). Mortality rate at study termination was 33% (2/6) in controls, 43% (6/14) in the warfarin group, and 60% (6/10) in the apixaban group. Animals died from extracerebral complications in most cases. Our study describes an experimental intracerebral hemorrhage model in the context of sustained hypertension and long-term anticoagulation. Extracerebral bleeding complications occurred more often in warfarin-treated animals compared with apixaban and control rats. PMID- 27189906 TI - Induction of epithelial to mesenchymal transition (EMT) and inhibition on adipogenesis: Two different sides of the same coin? Feasible roles and mechanisms of transforming growth factor beta1 (TGF-beta1) in age-related thymic involution. AB - Age-related thymic involution is characterized by a loss of thymic epithelial cells (TECs) and a concomitant increase in adipocytes, but the mechanisms involved in thymic adipogenesis are still not clear. Transforming growth factor beta1 (TGF-beta1) is a pleiotropic cytokine that has been reported to be up regulated with age in thymic stromal cells in both human and mouse. However, the exact role of TGF-beta1 in age-related thymic involution remains to be further elucidated. On the basis of previous findings, we propose a novel hypothesis that TGF-beta1 functions a dual role in age-related thymic involution. On one hand, up regulation of TGF-beta1 promotes epithelial to mesenchymal transition (EMT) process in TECs via activating forkhead box protein C2 (FoxC2). On the other hand, TGF-beta1 inhibits the transdifferentiation of EMT-derived mesenchymal cells to adipocytes in the thymus. If confirmed, our hypothesis will not only provide further evidence supporting that the transdifferentiation of TECs into pre-adipocytes represents a source of thymic adiposity during age-related thymic involution, but also uncover a unique role of TGF-beta1 in the transdifferentiation of TECs into pre-adipocytes. Collectively, the inhibition of TGF-beta1 may serve as a strategy to hinder age-related thymic involution or even to restore thymic function in the elderly. PMID- 27189907 TI - Adipokines, inflammatory mediators, and insulin-resistance parameters may not be good markers of metabolic syndrome after liver transplant. AB - OBJECTIVE: The role of adipokines in liver transplantation (LTx) recipients who have metabolic syndrome (MetS) has seldom been assessed. The aim of this study was to investigate the concentrations of adipokines, inflammatory mediators, and insulin-resistance markers in liver recipients with MetS and its components. METHODS: Serum samples from 34 patients (55.9% male; 54.9 +/- 13.9 y; 7.7 +/- 2.9 y after LTx; 50% presented with MetS) were assessed for adiponectin, resistin, tumor necrosis factor (TNF)-alpha, monocyte chemoattractant protein (MCP)-1, interleukin (IL)-6, C-reactive protein (CRP), homeostatic model assessment insulin resistance (HOMA-IR) and free fatty acid (FFA) levels. The dosages were uni- and multivariate analyzed to cover MetS (using the Harmonizing MetS criteria), its components, and dietary intake. RESULTS: A higher concentration of adiponectin (P < 0.05) was observed among patients with MetS (5.2 +/- 3.2 MUg/mL) compared with those without MetS (3.2 +/- 1.2 MUg/mL), as well as those with MetS components versus those without them: abdominal obesity (4.6 +/- 2.6 MUg/mL versus 2.6 +/- 0.6 MUg/mL), high triacylglycerols (TGs; 5.6 +/- 3.1 MUg/mL versus 3 +/- 0.9 MUg/mL) and low high-density lipoprotein (HDL; 6.1 +/- 2.7 MUg/mL versus 3.3 +/- 1.9 MUg/mL). Increased TNF-alpha and HOMA-IR values were seen in patients with abdominal obesity. Patients with high TGs also had greater FFA values. Independent predictors for adiponectin were waist-to-hip ratio, low HDL and high TGs. High TGs and fasting blood glucose were independent predictors for HOMA-IR. Independent predictors could not be identified for CRP, TNF-alpha, MCP 1, IL-6, or FFA. CONCLUSIONS: MetS and its components are related to an increased HOMA-IR concentration and FFA. Adiponectin, resistin, and inflammatory markers, such as TNF-alpha, IL-6, MCP-1, and CRP, were not associated with MetS in this sample of post-LTx patients. PMID- 27189908 TI - Adherence to the DASH and Mediterranean diets is associated with decreased risk for gestational diabetes mellitus. AB - OBJECTIVES: Few studies have examined the association between adherence to the Dietary Approaches to Stop Hypertension (DASH) or Mediterranean (MED) diets and prevalence of gestational diabetes mellitus (GDM). The aim of the present study was to evaluate the association between the two diets and GDM. METHODS: In a case control hospital-based study, pregnant women with (n = 200) and without (n = 260) GMD were recruited. An average of three 24-h dietary records were used to assess participants' dietary intakes. DASH scores were calculated based on the Fung method and MED scores were calculated using the Trichopoulou method. GDM was defined as fasting glucose >95 mg/dL or 1-h postprandial glucose >140 mg/dL for the first time in the pregnancy. The risk for GDM was assessed across tertiles of DASH and MED scores. RESULTS: DASH and MED diets were negatively related to fasting blood glucose, hemoglobin A1c, and serum triacylglycerol concentrations. High-density lipoprotein cholesterol was significantly higher for those in the top tertile of the DASH diet but not the MED diet in comparison with the lowest tertile. Total serum cholesterol level was lower in the third tertile of the MED diet but not in the DASH diet. Participants in the highest tertile of the MED diet had 80% lower risk for GDM compared with those in the lowest tertile (Ptrend = 0.006). Greater adherence to the DASH eating plan was associated with 71% reduced risk for GDM (Ptrend = 0.006) after adjustment for potential confounders. CONCLUSION: Adherence to either the DASH or Mediterranean diet is associated with decreased risk for GDM. PMID- 27189909 TI - Moderately high doses of the artificial sweetener saccharin potentially induce sleep disorders in mice. AB - OBJECTIVES: Caloric sweeteners such as sugar and honey are replaced in thousands of food products by noncaloric artificial sweeteners (NASs). The aim of the present study was to determine the effects of chronic NAS intake on circadian sleep regulation. METHODS: Circadian rhythms of sleep and locomotor activity were evaluated in mice after consumption of drinking water containing 0.1% (w/v) saccharin for 2 wk. RESULTS: The intake of saccharin ad libitum significantly reduced wakefulness and increased non-rapid eye movement sleep during the first half of the active (dark) phase, whereas wakefulness was significantly increased at the start of the sleep phase. Saccharin consumption obviously reduced spontaneous activity during the first half of the dark period. CONCLUSIONS: The findings suggest that NASs disturb the circadian sleep-wake cycle and cause behavioral inactivity in mice. PMID- 27189910 TI - Biologic Therapies and Risk of Infection and Malignancy in Patients With Inflammatory Bowel Disease: A Systematic Review and Network Meta-analysis. AB - BACKGROUND & AIMS: Safety issues are a major concern for patients considering treatments for inflammatory bowel disease (IBD). We performed a systematic review and meta-analysis to determine whether biologic agents affect the risk of infection or malignancy in adults with IBD. METHODS: We searched PubMed, Embase, Scopus, Cochrane IBD Group Specialized Trials Register, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov through March 2016 for randomized placebo-controlled or head-to-head trials of biologic agents approved for treatment of adults with IBD (ie, adalimumab, certolizumab, golimumab, infliximab, natalizumab, or vedolizumab). Two reviewers independently extracted study data and outcomes (serious infections, opportunistic infections, tuberculosis, any infection, and malignancies) and rated each trial's risk of bias. We used conventional meta-analysis to synthesize direct evidence and a network meta-analysis for adjusted indirect treatment comparisons. RESULTS: We identified 49 randomized placebo-controlled studies comprising 14,590 participants. Synthesis of the evidence indicated that patients treated with biologics had a moderate increase in risk of any infection (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.10-1.29) and a significant increase in risk of opportunistic infections (OR, 1.90; 95% CI, 1.21-3.01). Risk of serious infections was not increased in patients treated with biologics (OR, 0.89; 95% CI, 0.71-1.12). On the contrary, biologics appeared to significantly reduce risk of serious infections in studies with low risk of bias (OR, 0.56; 95% CI, 0.35 0.90). We did not find an increased risk of malignancy with use of biologic agents (OR, 0.90; 95% CI, 0.54-1.50), but data were insufficient in terms of exposure and follow-up times. None of the indirect comparisons, either among the individual agents or between the anti-tumor necrosis factor and anti-integrin classes, reached significance for any of the outcomes analyzed. CONCLUSIONS: On the basis of a systematic review and meta-analysis, biologic agents increase the risk of opportunistic infections in patients with IBD, but not the risk of serious infections. It is necessary to continue to monitor the comparative and long-term safety profiles of these drugs. PMID- 27189911 TI - Personalized Technologies in Chronic Gastrointestinal Disorders: Self-monitoring and Remote Sensor Technologies. AB - With increased access to high-speed Internet and smartphone devices, patients have started to use mobile applications (apps) for various health needs. These mobile apps are now increasingly used in integration with telemedicine and wearables to support fitness, health education, symptom tracking, and collaborative disease management and care coordination. More recently, evidence (especially around remote patient monitoring) has started to build in some chronic diseases, and some of the digital health technologies have received approval from the Food and Drug Administration. With the changing healthcare landscape and push for value-based care, adoption of these digital health initiatives among providers is bound to increase. Although so far there is a dearth of published evidence about effectiveness of these apps in gastroenterology care, there are ongoing trials to determine whether remote patient monitoring can lead to improvement in process metrics or outcome metrics for patients with chronic gastrointestinal diseases. PMID- 27189913 TI - Three-dimensional Printing in the Intestine. AB - Intestinal transplantation remains a life-saving option for patients with severe intestinal failure. With the advent of advanced tissue engineering techniques, great strides have been made toward manufacturing replacement tissues and organs, including the intestine, which aim to avoid transplant-related complications. The current paradigm is to seed a biocompatible support material (scaffold) with a desired cell population to generate viable replacement tissue. Although this technique has now been extended by the three-dimensional (3D) printing of geometrically complex scaffolds, the overall approach is hindered by relatively slow turnover and negative effects of residual scaffold material, which affects final clinical outcome. Methods recently developed for scaffold-free 3D bioprinting may overcome such obstacles and should allow for rapid manufacture and deployment of "bioprinted organs." Much work remains before 3D bioprinted tissues can enter clinical use. In this brief review we examine the present state and future perspectives of this nascent technology before full clinical implementation. PMID- 27189912 TI - Negative Effects on Psychological Health and Quality of Life of Genuine Irritable Bowel Syndrome-type Symptoms in Patients With Inflammatory Bowel Disease. AB - BACKGROUND & AIMS: Symptoms compatible with irritable bowel syndrome (IBS) are common in patients with inflammatory bowel disease (IBD), but it is unclear whether this relates to occult IBD activity. We attempted to resolve this issue in a secondary care population by using a cross-sectional study design. METHODS: We analyzed Rome III IBS symptoms, disease activity indices, and psychological, somatization, and quality of life data from 378 consecutive, unselected adult patients with IBD seen in clinics at St James's University Hospital in Leeds, United Kingdom from November 2012 through June 2015. Participants provided a stool sample for fecal calprotectin (FC) analysis; levels >=250 MUg/g were used to define mucosal inflammation. By using symptom data and FC levels we identified 4 distinct groups of patients: those with true IBS-type symptoms (IBS-type symptoms with FC levels <250 MUg/g, regardless of disease activity indices), quiescent IBD (no IBS-type symptoms with FC levels <250 MUg/g, regardless of disease activity indices), occult inflammation (normal disease activity indices and FC levels >=250 MUg/g, regardless of IBS symptom status), or active IBD (abnormal disease activity indices with FC levels >=250 MUg/g, regardless of IBS symptom status). We compared characteristics between these groups. RESULTS: Fifty seven of 206 patients with Crohn's disease (27.7%) and 34 of 172 patients with ulcerative colitis (19.8%) had true IBS-type symptoms. Levels of psychological comorbidity and somatization were significantly higher among patients with true IBS-type symptoms than patients with quiescent IBD or occult inflammation. Quality of life levels were also significantly reduced compared with patients with quiescent disease or occult inflammation and were similar to those of patients with active IBD. By using FC levels >=100 MUg/g to define mucosal inflammation, we found a similar effect of IBS-type symptoms on psychological health and quality of life. CONCLUSIONS: In a cross-sectional study, we identified a distinct group of patients with IBD and genuine IBS-type symptoms in the absence of mucosal inflammation. These symptoms had negative effects on psychological well-being and quality of life to the same degree as active IBD. New management strategies are required for this patient group. PMID- 27189914 TI - Endoscopic Therapy With Lumen-apposing Metal Stents Is Safe and Effective for Patients With Pancreatic Walled-off Necrosis. AB - BACKGROUND & AIMS: Endoscopic ultrasound-guided transmural drainage and necrosectomy have become the standard treatment for patients with pancreatic walled-off necrosis (WON). Lumen-apposing metal stents (LAMS) have shown success in the management of pancreatic fluid collections. However, there are few data on their specific roles in management of WON. We investigated the efficacy and safety of LAMS in treatment of WON. METHODS: We performed a retrospective multicenter case series of 124 patients with WON who underwent endoscopic transmural drainage by using LAMS at 17 tertiary care centers from January 2014 through May 2015. Patients underwent endoscopic ultrasound-guided cystogastrostomy or cystoenterostomy with placement of an LAMS into the WON collection. At the discretion of the endoscopist, we performed direct endoscopic necrosectomy, irrigation with hydrogen peroxide, and/or nasocystic drain placement. We performed endoscopic retrograde cholangiopancreatography with pancreatic duct stent placement when indicated. Concomitant therapies included direct endoscopic debridement (n = 78), pancreatic duct stent placement for leak (n = 19), hydrogen peroxide-assisted necrosectomy (n = 38), and nasocystic irrigation (n = 22). We collected data for a median time of 4 months (range, 1-34 months) after the LAMS placement. The primary outcomes were rates of technical success (successful placement of the LAMS), clinical success (resolution of WON, on the basis of image analysis, without need for further intervention via surgery or interventional radiology), and adverse events. RESULTS: The median size of the WON was 9.5 cm (range, 4-30 cm). Eight patients had 2 LAMS placed for multiport access, all with technical success (100%). Clinical success was achieved in 107 patients (86.3%) after 3 months of follow-up. Thirteen patients required a percutaneous drain, and 3 required a surgical intervention to manage their WON. The stents remained patent in 94% of patients (117 of 124) and migrated in 5.6% of patients (7 of 124). The median number of endoscopic interventions was 2 (range, 1-9 interventions). CONCLUSIONS: On the basis of a retrospective analysis of 124 patients, endoscopic therapy of WON by using LAMS is safe and effective. Creation of a large and sustained cystogastrostomy or cystoenterostomy tract is effective in the drainage and treatment of WON. PMID- 27189916 TI - Appropriateness of Testing for Anti-Tumor Necrosis Factor Agent and Antibody Concentrations, and Interpretation of Results. AB - BACKGROUND & AIMS: The availability of tests for blood concentrations of anti tumor necrosis factor (TNF) agents and antibodies against these drugs could improve dose selection for patients with inflammatory bowel disease (IBD). However, there is little consensus on when to test and how to interpret test results. We used the RAND/UCLA Appropriateness Method to determine when these tests are appropriate and how to clinically interpret their results. METHODS: We conducted a systematic literature search in November 2013 to identify observational or experimental studies of the measurement of anti-TNF drug and antibody concentrations in patients with IBD and interpretation of their results. We developed 35 scenarios that assessed the appropriateness of testing and 143 scenarios that addressed clinical strategies in response to test results, and presented the findings to an expert panel. The appropriateness of each scenario was rated before and after an in-person meeting with the panel. Panelists rated the appropriateness of various clinical management options including changing therapy within class, switching out of class, adjusting drug dose or interval, adding or adjusting concomitant immune modulators, and doing nothing for each of 6 permutations of high versus low drug concentrations and high, low, or undetectable antibody concentrations. Disagreement was assessed using a validated index. RESULTS: Assessment of anti-TNF drug and antibody concentrations was rated appropriate at the end of induction therapy in primary nonresponders, in secondary nonresponders, at least once during the first year of maintenance therapy, and following a drug holiday. Routine assessment in responders at the end of induction was rated uncertain. In nearly all scenarios, escalation of drug dosing was rated appropriate when drug concentration was low in the absence of antibodies, and switching within class was rated appropriate when antibodies were present. Other recommendations depended on the specific clinical scenario for which the test was obtained. CONCLUSIONS: Based on the RAND/UCLA Appropriateness Method of analysis, an expert panel recommends testing for drug and antibody concentrations in many clinical scenarios. The appropriate timing and best way to respond to anti-TNF drug and antibody testing for IBD depends on the specific clinical scenario. These recommendations can help guide clinicians to best optimize anti-TNF therapy. PMID- 27189915 TI - A Model to Identify Sarcopenia in Patients With Cirrhosis. AB - BACKGROUND & AIMS: The severe depletion of muscle mass at the third lumbar vertebral level (sarcopenia) is a marker of malnutrition and is independently associated with mortality in patients with cirrhosis. Instead of monitoring sarcopenia by cross-sectional imaging, we investigated whether ultrasound-based measurements of peripheral muscle mass, measures of muscle function, along with nutritional factors, are associated with severe loss of muscle mass. METHODS: We performed a prospective study of 159 outpatients with cirrhosis (56% male; mean age, 58 +/- 10 years; mean model for end-stage liver disease score, 10 +/- 3; 60% Child-Pugh class A) evaluated at the Cirrhosis Care Clinic at the University of Alberta Hospital from March 2011 through September 2012. Lumbar skeletal muscle indices were determined by computed tomography or magnetic resonance imaging. We collected clinical data and data on patients' body composition, nutrition, and thigh muscle thickness (using ultrasound analysis). We also measured mid-arm muscle circumference, mid-arm circumference, hand grip, body mass index, and serum level of albumin; patients were evaluated using the subjective global assessment scale. Findings from these analyses were compared with those from cross-sectional imaging, for each sex, using logistic regression analysis. RESULTS: Based on cross-sectional imaging analysis, 43% of patients had sarcopenia (57% of men and 25% of women). Results from the subjective global assessment, serum level of albumin, and most nutritional factors were significantly associated with sarcopenia. We used multivariate analysis to develop a model to identify patients with sarcopenia, and developed a nomogram based on body mass index and thigh muscle thickness for patients of each sex. Our model identified men with sarcopenia with an area under the receiver operating characteristic curve value of 0.78 and women with sarcopenia with an area under the receiver operating characteristic curve value of 0.89. CONCLUSIONS: In a prospective study of patients with cirrhosis, we found that the combination of body mass index and thigh muscle thickness (measured by ultrasound) can identify male and female patients with sarcopenia almost as well as cross-sectional imaging (area under the receiver operating characteristic curve values of 0.78 and 0.89, respectively). These factors might be used in screening and routine nutritional monitoring of patients with cirrhosis. PMID- 27189918 TI - Characterization of the gene encoding a fibrinogen-related protein expressed in Crassostrea gigas hemocytes. AB - Four exons of the CgFrep1 gene (3333 bp long) encode a putative fibrinogen related protein (324 aa) bearing a single C-terminal FBG domain. Transcripts of the gene obtained from hemocytes of different Pacific oysters show prominent individual variation based on SNP and indels of tandem repeats resulted in polymorphism of N-terminus of the putative CgFrep1 polypeptide. The polypeptide chain bears N-terminal coiled-coil region potentially acting as inter-subunit interface in the protein oligomerization. It is suggested that CgFrep1 gene encodes the oligomeric lectin composed of at least two subunits. PMID- 27189917 TI - The mucosal expression signatures of g-type lysozyme in turbot (Scophthalmus maximus) following bacterial challenge. AB - The mucosal surfaces constitute the first line of host defense against infection, and also serve as the dynamic interfaces that simultaneously mediate a diverse array of critical physiological processes, while in constantly contact with a wide range of pathogens. The lysozymes are considered as key components for innate immune response to pathogen infection with their strong antibacterial activities. But their activities in mucosal immune responses were always overlooked, especially for g-type lysozymes, whose expression patterns in mucosal tissues following bacterial challenge are still limited. Towards to this end, here, we characterized the g-type lysozymes, Lyg1 and Lyg2 in turbot, and determined their expression patterns in mucosal barriers following different bacterial infection. The phylogenetic analysis revealed the turbot g-type lysozyme genes showed the closest relationship to Cynoglossus semilaevis. The two lysozyme genes showed different expression patterns following challenge. Lyg2 was significantly up-regulated in mucosal tissues following Vibrio anguillarum and Streptococcus iniae challenge, while Lyg1 showed a general trend of down regulation. The significant mucosal expression signatures of g-type lysozyme genes indicated their key roles to prevent pathogen attachment and entry in the first line of host defense system. Further functional studies should be carried out to better characterize the availability of utilization of g-type lysozyme to increase the disease resistance in the mucosal surfaces and facilitate the disease resistant breeding selection. PMID- 27189919 TI - Residual total pancreatectomy: Short- and long-term outcomes. AB - BACKGROUND/OBJECTIVES: Because of limited numbers of patients, there are limited data available regarding outcomes after residual total pancreatectomy (R-TP). This study aimed to assess outcomes after the R-TP vs the one-stage total pancreatectomy (O-TP), especially focused on the pancreatic adenocarcinoma cases. METHODS: From 2005 to 2014, all patients who underwent the R-TP (n = 8) and the O TP (n = 12) for pancreatic primary malignancy were prospectively enrolled. RESULTS: The median time from the initial operation to the R-TP was 30 months. Ten patients in the O-TP group and 8 in the R-TP had pancreatic adenocarcinoma. Postoperative complications occurred in two O-TP patients and one R-TP patient. There was no in-hospital mortality. At 12 months after surgery, the median insulin dose was 27 U/day after the O-TP and 24 U/day after the R-TP, the median hemoglobin A1c was 7.2% after the O-TP and 6.9% after the R-TP. There was a significantly larger reduction in body weight after the O-TP than after the R-TP. Postoperative fatty liver disease occurred in about half of the patients in each group. In patients with pancreatic adenocarcinoma, the 2-year overall survival rate was not significantly different (68.6% after the O-TP vs 71.4% after the R TP). CONCLUSIONS: Although the postoperative morbidity and nutritional statuses should be improved, these favorable short- and long-term outcomes demonstrate that the R-TP is a feasible procedure for patients with malignant tumor in the remnant pancreas. PMID- 27189920 TI - How Prepared Are Hospitals' Emergency Management Capacity? Factors Influencing Efficiency of Disaster Rescue. AB - OBJECTIVES: In light of government investment over the past decade, we explored the capacity for disaster response in Heilongjiang Province, identifying the factors that affect response capacity. METHODS: We surveyed 1257 medical staff in 65 secondary and tertiary hospitals in Heilongjiang province to explore their perceptions of disaster management capacity using a cross-sectional multistage, stratified cluster sampling method. RESULTS: All tertiary hospitals (100%) and most secondary hospitals (93%) have documented disaster management plans that are regularly reviewed. In secondary hospitals, drills were less prevalent (76.7%) but the occurrence of simulated training exercises was closer to tertiary hospitals (86.0%). We noted that 95.4% of all hospitals have leadership groups responsible for disaster preparedness capacity building, but only 10.8% have a stockpiled network of reserve supplies. CONCLUSIONS: Although response capacity has improved in Heilongjiang Province, vulnerabilities remain. We recommend that priorities should be targeted at preparedness capacity building, in terms of reliable and relevant operational response plans, the expansion of existing response mechanisms to oversee local education and scenario training, and to ensure there is sufficient access to protective equipment and materials, either held in reserve, or alternatively by activating resilient supply chain mechanisms. (Disaster Med Public Health Preparedness. 2018;12:176-183). PMID- 27189921 TI - Tungstate as a Transition State Analog for Catalysis by Alkaline Phosphatase. AB - The catalytic mechanisms underlying Escherichia coli alkaline phosphatase's (AP) remarkable rate enhancement have been probed extensively. Past work indicated that whereas the serine nucleophile (Ser102) electrostatically repels the product phosphate, another oxyanion, tungstate, binds more strongly in the presence of Ser102. These results predict a covalent bond between the serine nucleophile and tungstate, a model that we test herein. The crystal structure of tungstate-bound alkaline phosphatase provides evidence for a covalent adduct model and further shows that the ligand adopts trigonal bipyramidal geometry, which is infrequently observed for tungstate in small molecules and other active sites but mirrors the geometry of the presumed phosphoryl transfer transition state. The AP active site is known to stabilize another oxyanion, vanadate, in trigonal bipyramidal geometry, but the extent to which binding of either ligand reproduces the energetics of the transition state cannot be deduced from structural inspection alone. To test for transition state analog behavior, we determined the relationship between catalytic activity and affinity for tungstate and vanadate for a series of 20 AP variants. Affinity and activity were highly correlated for tungstate (r(2) = 0.89) but not vanadate (r(2) = 0.23), indicating that the tungstate*AP complex may better mimic this enzyme's transition state properties. The results herein suggest that tungstate will be a valuable tool for further dissecting AP catalysis and may prove helpful in mechanistic studies of other phosphoryl transfer enzymes. PMID- 27189923 TI - Use of the Delta plate for surgical treatment of patients with condylar fractures. AB - PURPOSE: The purpose of this study was to summarize the results of our own experience in the application of the Delta plate for surgical treatment of condylar fractures. MATERIAL AND METHODS: The research was carried out in 42 patients of the Department for Maxillofacial Surgery, Hospital of the Ministry of Interior in Kielce (Poland), who were surgically treated in the years 2013-2015 after a unilateral condylar fracture. To be qualified for surgery patients fulfilled at least two of the following criteria: (1) presence of occlusal disorders, (2) presence of displacement of fragments, (3) height decrease of the mandibular ramus of over 4 mm, or (4) dislocation of the temporomandibular joint. The first of the above criteria (clinical criterion) was treated as the basic one, and the others were established based on radiological examinations. For all patients, a Delta plate fixed with four 2.0-mm screws was applied in order to achieve a stable osteosynthesis of the fracture. Clinical studies were carried out in all patients on the first day after the surgery, as well as after 1, 3, and 6 months. RESULTS: The results presented in this study were based on an analysis of the most extensive research material in Poland (n = 42). All patients presented correct mandible mobility on all three planes, and the range of abduction after the conclusion of the treatment (i.e., 6 months after the surgery) amounted to average 47 mm (range 45-54 mm). In none of the cases analyzed in our study was there a breaking of the Delta plate. A rare complication observed in our own experience was the loosening and partial removal of one of the fastening screws from the bone and from the hole in the plate. This failure was observed in three patients (7%). CONCLUSIONS: The application of the Delta plate for the stable osteosynthesis of condylar fractures ensures fully satisfactory treatment results, both from the radiological and the clinical points of view. The use of Delta plates does not involve any significant complications. There is practically no risk of a breaking of the plate, and failures in form of the loosening of the retaining screws are very rare and do not cause any significant disturbances in the fracture healing process. PMID- 27189924 TI - Le Fort 1 osteotomy and calvarial bone grafting for severely resorbed maxillae. AB - INTRODUCTION: Long standing maxillary edentulism leads to alveolar ridge resorption which prevent implant placement and causes prosthetic malocclusion. The aim of the study was to assess vertical and transversal bone increase following Le Fort 1 osteotomy associated with calvarial bone grafting. MATERIALS AND METHODS: 66 patients who presented severely atrophic maxillae were treated with Le Fort 1 osteotomy with bone grafting from 2003 to 2014. Vertical and transversal bone level was measured preoperatively and 6 months post-operatively to calculate the alveolar ridge augmentation. Follow up ranged from 10 months to 11 years. RESULTS: The mean increase of bone height was 9.3 mm and the mean increase of bone width was 6 mm 417 endosseous implants were placed in the grafted maxilla. Mean endosseous implant length was of 10.7 mm at the first molar site (range: 8-16 mm). A total of 25 implants failed, the overall implant survival rate is of 94%. The definitive prosthetis was fixed in 65% of the patients and removable in 35% of the patients. DISCUSSION: Le Fort 1 osteotomy associated with calvarial bone grafting is the main treatment option able to offer fixed bridge and perfect class 1 occlusion in cases of severe maxillary atrophy. PMID- 27189922 TI - Rodent-Adapted Filoviruses and the Molecular Basis of Pathogenesis. AB - Ebola, Marburg, and Ravn viruses, all filoviruses, are the causative agents of severe hemorrhagic fever. Much of what we understand about the pathogenesis of filovirus disease is derived from work with animal models, including nonhuman primates, which are considered the "gold standard" filovirus model since they faithfully recapitulate the clinical hallmarks of filovirus disease. However, rodent models, including the mouse, guinea pig, and hamster, also exist for Ebola, Marburg, and Ravn viruses, and although they may not reproduce all the clinical signs of filovirus disease, thanks to their relative ease of use and low cost, they are often the first choice for initial descriptions of virus pathogenesis and evaluation of antiviral prophylactics and therapeutics. Since filoviruses do not cause significant disease in adult, immunocompetent rodents, these models rely on "rodent-adapted" viruses that have been passaged several times through their host until virulence and lethality are achieved. In the process of adaptation, the viruses acquire numerous nucleotide/amino acid mutations that contribute to virulence in their rodent host. Interestingly, virus protein 24 (VP24) and nucleoprotein (NP) appear to be major virulence factors for ebolaviruses in rodents, whereas VP40 appears to be the major virulence factor for marburgviruses. By characterizing these mutations and understanding the molecular mechanisms that lead to the acquisition of virulence, we can gain better insight into the pathogenic processes that underlie filovirus disease in humans. These processes, and the viral and/or cellular proteins that contribute to them, will make attractive targets for the development of novel therapeutics and counter-measures. PMID- 27189926 TI - Sickness behaviour in the cricket Gryllus texensis: Comparison with animals across phyla. AB - Immune activation alters behaviour (i.e. sickness behaviour) in animals across phyla and is thought to aid recovery from infection. Hypotheses regarding the adaptive function of different sickness behaviours (e.g. decreased movement and appetite) include the energy conservation and predator avoidance hypotheses. These hypotheses were originally developed for mammals (e.g. Hart, 1988), however similar sickness behaviours are also observed in insects (e.g., crickets). We predicted that immune-challenged crickets (Gryllus texensis) would reduce feeding, grooming, and locomotion as well as increase shelter use, consistent with the energy conservation and predator avoidance hypotheses. We found evidence of illness-induced anorexia in adult and juvenile crickets, consistent with previous research (Adamo et al., 2010), but contrary to expectations, we found an increase in grooming, and no evidence that crickets decreased locomotion or increased shelter use in response to immune challenge. Therefore, our results do not support the energy conservation or predator avoidance hypotheses. The difference in sickness behaviour between insects and mammals is probably due, in part, to the lack of physiological fever in insects. We hypothesize that the lack of physiological fever reduces the need for energy conservation, decreasing the benefits of some sickness behaviours such as increased shelter use. These results, taken together with others in the literature, suggest that ectotherms and endotherms may differ significantly in the selective forces leading to the evolution of most sickness behaviours. PMID- 27189925 TI - Entomological assessment of yellow fever-epidemic risk indices in Benue State, Nigeria, 2010-2011. AB - Yellow fever (YF) is a vector-borne disease affecting humans and non-human primates in tropical areas. In the past, there have been pockets of YF outbreaks in Nigeria that resulted in preventable deaths. Surveillance efforts towards avoiding another outbreak have been put in place with the aim of early detection and control. However, risk indices relating to the density of immature YF mosquito vectors are given little consideration even though it is the first step in curbing a possible outbreak. Immature collections from 1538 houses in Ega, Oju, Otukpoicho and Otukpo in Benue State were carried out in 2010 and 2011. Risk indices such as house index (HI), container index (CI) and Breteau index (BI) were estimated. Molecular detection of YF was carried out on randomly selected Aedes larvae and pupae. Overall, 431,381 mosquitoes were collected in and around house premises. Thirteen species were identified: Ae. aegypti (Linneaus), Ae. africanus (Theobald), Ae. albopictus (Skuse), Ae. cumminsii (Theobald), Ae. luteocephalus (Newstead), Ae. simpsoni s.l. (Theobald), Ae. vittatus (Bigot), Anopheles gambiae Giles, An. nili (Theobald), Cx. nebulosus Theobald, Culex quinquefasciatus Say, Lutzia tigripes (Grandpre and Charmoy) and Toxorhynchites brevipalpis Theobald. The HI, CI and BI for Ae. aegypti were high in all the study locations, but low for Ae. lueteocephalus except in Ega. With 50 immature Aedes mosquitoes screened across locations, only Ae. aegypti from Ega were positive for YF. This study places Ega on a high alert of an impending YF outbreak. Thus, urgent steps to clear this area of potential mosquito sites are highly recommended. PMID- 27189927 TI - "Pseudoprogression" of Pulmonary Pleomorphic Carcinoma during Nivolumab Therapy. PMID- 27189928 TI - The Loop Technique: Addressing Celiac Artery Dissection in a Branched and Fenestrated Endograft for the Treatment of a Type III Thoracoabdominal Aneurysm. AB - PURPOSE: To describe a bailout technique for use during branched/fenestrated thoracoabdominal aortic aneurysm (TAAA) repair to address celiac artery (CA) dissection. TECHNIQUE: The technique is demonstrated in a 69-year-old man who underwent fenestrated stent-graft repair of a 6-cm type III TAAA. The main fenestrated stent-graft was positioned without difficulty, and the renal and superior mesenteric arteries were stented. A stent-graft was placed in the CA, but angiography showed the vessel to be occluded by dissection beyond the stent graft. Wire manipulations to regain access to the true lumen culminated in perforation. At this point, the gastroduodenal artery was catheterized with a 0.035-inch guidewire, which was advanced in retrograde fashion into the CA true lumen and then snared back to the left brachial artery forming a loop. After exchange for a 0.014-inch system, self-expanding stents were deployed into the hepatic artery. Postoperative recovery was uneventful, and the patient was discharged on day 6. At 1-year follow-up, the patient was doing very well. Imaging demonstrated no endoleak, no graft migration, and sac shrinkage to a diameter of 5.1 cm. CONCLUSION: The "loop technique" can be a very useful and effective bailout maneuver in regaining access to the true lumen of a dissected CA in patients undergoing branched/fenestrated thoracoabdominal aortic aneurysm repair. PMID- 27189929 TI - Retinal Sensitivity at the Junctional Zone of Eyes With Geographic Atrophy Due to Age-Related Macular Degeneration. AB - PURPOSE: To compare the retinal sensitivity at the junctional zone and uninvolved retina of eyes with geographic atrophy (GA) due to age-related macular degeneration (AMD). DESIGN: Cross-sectional, observational study. METHODS: Patients with dry AMD were evaluated by microperimetry and Cirrus optical coherence tomography (OCT). The GA lesion was segmented on en face OCT images and registered to color images with the microperimetric sensitivity values. The junctional zone, a ring 500 MUm in width, surrounding the region of atrophy was further subdivided into "subzones": Zone 1 at the precise border of atrophy; Zone 2 as the center of this junctional region; Zone 3 at the border between the junctional zone and adjacent "normal" retina. An additional Zone 4 was defined as "normal" retina, at least 500 MUm from the edge of the GA lesion. The mean sensitivities of all stimuli within each of these zones (across the entire cohort) were compared. RESULTS: In 36 eyes with GA, the mean retinal sensitivity in the various subzones was as follows: Zone 1 = 13.7 +/- 4.7, Zone 2 = 20.3 +/- 3.9, Zone 3 = 20.9 +/- 3.9, and Zone 4= 21.1 +/- 4.1 (all in dB). Zone 1 (atrophic margin) sensitivity was significantly lower than all other zones (P < .001 for all comparisons), but there were no differences between the other zones. CONCLUSION: Retinal sensitivity appears to drop precipitously at the margins of GA lesions. The retinal sensitivity in the bulk of the junctional zone is similar to apparently uninvolved distant regions. PMID- 27189930 TI - Pars Plana Vitrectomy Combined With Either Secondary Scleral-Fixated or Anterior Chamber Intraocular Lens Implantation. AB - PURPOSE: To compare visual outcomes among eyes that underwent pars plana vitrectomy (PPV) in combination with either anterior chamber intraocular lens implantation (ACIOL) or scleral suturing of posterior chamber lens (PCIOL). DESIGN: Retrospective comparative case series. METHODS: All eyes presented with aphakia or luxated or subluxated posterior chamber intraocular lens (IOL) following complicated cataract surgery, trauma, or spontaneous dislocation. Eyes involving visually significant macular pathology, past retinal detachment, follow up of less than 6 months, and surgeries requiring the removal of an ACIOL were excluded. The main outcomes measured were final best-corrected visual acuity (BCVA) and surgical complication rates. RESULTS: Fifty-seven eyes met inclusion criteria; median follow-up was 13.2 months. Initial median BCVA for ACIOL patients was logMAR 1.301 (Snellen equivalent 20/400, range 20/20 to light perception); final median BCVA was logMAR 0.477 (Snellen equivalent 20/60, range 20/20 to light perception, P < .001). Initial median BCVA for PCIOL patients was logMAR 1.239 (Snellen equivalent 20/347, range 20/60 to light perception); final median BCVA was logMAR 0.301 (Snellen equivalent 20/40, range 20/20 to hand motions, P < .001). The change in BCVA between the 2 groups over the course of the study was similar (P > .05). More epiretinal membrane (ERM) formations occurred postoperatively in the ACIOL group (P = .011). Other complication rates were similar between both groups. CONCLUSIONS: PPV with secondary IOL placement is safe and effective, resulting in improved visual outcomes regardless of the technique used. Patients undergoing ACIOL placement have a higher incidence of ERM formation. PMID- 27189931 TI - Choroidal and Retinal Thickness in Children With Different Refractive Status Measured by Swept-Source Optical Coherence Tomography. AB - PURPOSE: To investigate the choroidal and retinal thickness in myopic, emmetropic, and hyperopic Chinese children by swept-source longer-wavelength optical coherence tomography. DESIGN: Cross-sectional study. METHODS: Two-hundred and seventy-six schoolchildren aged 7-13 years underwent comprehensive ophthalmic examinations, including cycloplegic refraction, and swept-source optical coherence tomography measurements. The thickness of the choroid, retina, ganglion cell layer, and nerve fiber layer were compared among children of different refractive status. The topographic variation and factors related to the thickness of the choroid and retinal layers were analyzed. RESULTS: Compared to emmetropic subjects, those with myopia had a significantly thinner choroid in all regions (P < .01), and hyperopic subjects had a thicker choroid in most regions (P < .05). The myopic retinas were thinner than those of emmetropic or hyperopic subjects in the superior parafoveal and all 4 perifoveal subfields (P < .05), but no other subfields differed significantly among different refractive groups (P > .05). The axial length and refractive diopters were independently related to central foveal choroidal thickness (R(2) = 0.17, P < .01), while age and intraocular pressure were independently associated with central fovea retinal (R(2) = 0.15, P < .01) and ganglion cell layer thicknesses (R(2) = 0.10, P < .01) after adjustment for other systematic and ocular factors. Central foveal choroidal and retinal thickness were unrelated in children of different refractive status (P > .05). CONCLUSIONS: Choroidal thickness, but not retinal thickness, correlated closely with axial length and refractive diopters in Chinese children. Choroid thinning occurs before retina thinning early in myopic progression. PMID- 27189933 TI - Emerging role for regulated in development and DNA damage 1 (REDD1) in the regulation of skeletal muscle metabolism. AB - Since its discovery, the protein regulated in development and DNA damage 1 (REDD1) has been implicated in the cellular response to various stressors. Most notably, its role as a repressor of signaling through the central metabolic regulator, the mechanistic target of rapamycin in complex 1 (mTORC1) has gained considerable attention. Not surprisingly, changes in REDD1 mRNA and protein have been observed in skeletal muscle under various physiological conditions (e.g., nutrient consumption and resistance exercise) and pathological conditions (e.g., sepsis, alcoholism, diabetes, obesity) suggesting a role for REDD1 in regulating mTORC1-dependent skeletal muscle protein metabolism. Our understanding of the causative role of REDD1 in skeletal muscle metabolism is increasing mostly due to the availability of genetically modified mice in which the REDD1 gene is disrupted. Results from such studies provide support for an important role for REDD1 in the regulation of mTORC1 as well as reveal unexplored functions of this protein in relation to other aspects of skeletal muscle metabolism. The goal of this work is to provide a comprehensive review of the role of REDD1 (and its paralog REDD2) in skeletal muscle during both physiological and pathological conditions. PMID- 27189934 TI - Perilipin 5 is dispensable for normal substrate metabolism and in the adaptation of skeletal muscle to exercise training. AB - Cytoplasmic lipid droplets provide a reservoir for triglyceride storage and are a central hub for fatty acid trafficking in cells. The protein perilipin 5 (PLIN5) is highly expressed in oxidative tissues such as skeletal muscle and regulates lipid metabolism by coordinating the trafficking and the reversible interactions of effector proteins at the lipid droplet. PLIN5 may also regulate mitochondrial function, although this remains unsubstantiated. Hence, the aims of this study were to examine the role of PLIN5 in the regulation of skeletal muscle substrate metabolism during acute exercise and to determine whether PLIN5 is required for the metabolic adaptations and enhancement in exercise tolerance following endurance exercise training. Using muscle-specific Plin5 knockout mice (Plin5(MKO)), we show that PLIN5 is dispensable for normal substrate metabolism during exercise, as reflected by levels of blood metabolites and rates of glycogen and triglyceride depletion that were indistinguishable from control (lox/lox) mice. Plin5(MKO) mice exhibited a functional impairment in their response to endurance exercise training, as reflected by reduced maximal running capacity (20%) and reduced time to fatigue during prolonged submaximal exercise (15%). The reduction in exercise performance was not accompanied by alterations in carbohydrate and fatty acid metabolism during submaximal exercise. Similarly, mitochondrial capacity (mtDNA, respiratory complex proteins, citrate synthase activity) and mitochondrial function (oxygen consumption rate in muscle fiber bundles) were not different between lox/lox and Plin5(MKO) mice. Thus, PLIN5 is dispensable for normal substrate metabolism during exercise and is not required to promote mitochondrial biogenesis or enhance the cellular adaptations to endurance exercise training. PMID- 27189935 TI - No insulating effect of obesity. AB - The development of obesity may be aggravated if obesity itself insulates against heat loss and thus diminishes the amount of food burnt for body temperature control. This would be particularly important under normal laboratory conditions where mice experience a chronic cold stress (at ~20 degrees C). We used Scholander plots (energy expenditure plotted against ambient temperature) to examine the insulation (thermal conductance) of mice, defined as the inverse of the slope of the Scholander curve at subthermoneutral temperatures. We verified the method by demonstrating that shaved mice possessed only half the insulation of nonshaved mice. We examined a series of obesity models [mice fed high-fat diets and kept at different temperatures, classical diet-induced obese mice, ob/ob mice, and obesity-prone (C57BL/6) vs. obesity-resistant (129S) mice]. We found that neither acclimation temperature nor any kind or degree of obesity affected the thermal insulation of the mice when analyzed at the whole mouse level or as energy expenditure per lean weight. Calculation per body weight erroneously implied increased insulation in obese mice. We conclude that, in contrast to what would be expected, obesity of any kind does not increase thermal insulation in mice, and therefore, it does not in itself aggravate the development of obesity. It may be discussed as to what degree of effect excess adipose tissue has on insulation in humans and especially whether significant metabolic effects are associated with insulation in humans. PMID- 27189932 TI - Insights into the role of neuronal glucokinase. AB - Glucokinase is a key component of the neuronal glucose-sensing mechanism and is expressed in brain regions that control a range of homeostatic processes. In this review, we detail recently identified roles for neuronal glucokinase in glucose homeostasis and counterregulatory responses to hypoglycemia and in regulating appetite. We describe clinical implications from these advances in our knowledge, especially for developing novel treatments for diabetes and obesity. Further research required to extend our knowledge and help our efforts to tackle the diabetes and obesity epidemics is suggested. PMID- 27189936 TI - Negatively Charged Lipids as a Potential Target for New Amphiphilic Aminoglycoside Antibiotics: A BIOPHYSICAL STUDY. AB - Bacterial membranes are highly organized, containing specific microdomains that facilitate distinct protein and lipid assemblies. Evidence suggests that cardiolipin molecules segregate into such microdomains, probably conferring a negative curvature to the inner plasma membrane during membrane fission upon cell division. 3',6-Dinonyl neamine is an amphiphilic aminoglycoside derivative active against Pseudomonas aeruginosa, including strains resistant to colistin. The mechanisms involved at the molecular level were identified using lipid models (large unilamellar vesicles, giant unilamelllar vesicles, and lipid monolayers) that mimic the inner membrane of P. aeruginosa The study demonstrated the interaction of 3',6-dinonyl neamine with cardiolipin and phosphatidylglycerol, two negatively charged lipids from inner bacterial membranes. This interaction induced membrane permeabilization and depolarization. Lateral segregation of cardiolipin and membrane hemifusion would be critical for explaining the effects induced on lipid membranes by amphiphilic aminoglycoside antibiotics. The findings contribute to an improved understanding of how amphiphilic aminoglycoside antibiotics that bind to negatively charged lipids like cardiolipin could be promising antibacterial compounds. PMID- 27189937 TI - Immunoresponsive Gene 1 and Itaconate Inhibit Succinate Dehydrogenase to Modulate Intracellular Succinate Levels. AB - Metabolic reprogramming is emerging as a hallmark of the innate immune response, and the dynamic control of metabolites such as succinate serves to facilitate the execution of inflammatory responses in macrophages and other immune cells. Immunoresponsive gene 1 (Irg1) expression is induced by inflammatory stimuli, and its enzyme product cis-aconitate decarboxylase catalyzes the production of itaconate from the tricarboxylic acid cycle. Here we identify an immunometabolic regulatory pathway that links Irg1 and itaconate production to the succinate accumulation that occurs in the context of innate immune responses. Itaconate levels and Irg1 expression correlate strongly with succinate during LPS exposure in macrophages and non-immune cells. We demonstrate that itaconate acts as an endogenous succinate dehydrogenase inhibitor to cause succinate accumulation. Loss of itaconate production in activated macrophages from Irg1(-/-) mice decreases the accumulation of succinate in response to LPS exposure. This metabolic network links the innate immune response and tricarboxylic acid metabolism to function of the electron transport chain. PMID- 27189938 TI - Thiopurine Prodrugs Mediate Immunosuppressive Effects by Interfering with Rac1 Protein Function. AB - 6-Thiopurine (6-TP) prodrugs include 6-thioguanine and azathioprine. Both are widely used to treat autoimmune disorders and certain cancers. This study showed that a 6-thioguanosine triphosphate (6-TGTP), converted in T-cells from 6-TP, targets Rac1 to form a disulfide adduct between 6-TGTP and the redox-sensitive GXXXXGK(S/T)C motif of Rac1. This study also showed that, despite the conservation of the catalytic activity of RhoGAP (Rho-specific GAP) on the 6-TGTP Rac1 adduct to produce the biologically inactive 6-thioguanosine diphosphate (6 TGDP)-Rac1 adduct, RhoGEF (Rho-specific GEF) cannot exchange the 6-TGDP adducted on Rac1 with free guanine nucleotide. The biologically inactive 6-TGDP-Rac1 adduct accumulates in cells because of the ongoing combined actions of RhoGEF and RhoGAP. Because other Rho GTPases, such as RhoA and Cdc42, also possess the GXXXXGK(S/T)C motif, the proposed mechanism for the inactivation of Rac1 also applies to RhoA and Cdc42. However, previous studies have shown that CD3/CD28 stimulated T-cells contain more activated Rac1 than other Rho GTPases such as RhoA and Cdc42. Accordingly, Rac1 is the main target of 6-TP in activated T cells. This explains the T-cell-specific Rac1-targeting therapeutic action of 6 TP that suppresses the immune response. This proposed mechanism for the action of 6-TP on Rac1 performs a critical role in demonstrating the capability to design a Rac1-targeting chemotherapeutic agent(s) for autoimmune disorders. Nevertheless, the results also suggest that the targeting action of other Rho GTPases in other organ cells, such as RhoA in vascular cells, may be linked to cytotoxicities because RhoA plays a key role in vasculature functions. PMID- 27189939 TI - Crystal Structure of a Two-domain Fragment of Hepatocyte Growth Factor Activator Inhibitor-1: FUNCTIONAL INTERACTIONS BETWEEN THE KUNITZ-TYPE INHIBITOR DOMAIN-1 AND THE NEIGHBORING POLYCYSTIC KIDNEY DISEASE-LIKE DOMAIN. AB - Hepatocyte growth factor activator inhibitor-1 (HAI-1) is a type I transmembrane protein and inhibitor of several serine proteases, including hepatocyte growth factor activator and matriptase. The protein is essential for development as knock-out mice die in utero due to placental defects caused by misregulated extracellular proteolysis. HAI-1 contains two Kunitz-type inhibitor domains (Kunitz), which are generally thought of as a functionally self-contained protease inhibitor unit. This is not the case for HAI-1, where our results reveal how interdomain interactions have evolved to stimulate the inhibitory activity of an integrated Kunitz. Here we present an x-ray crystal structure of an HAI-1 fragment covering the internal domain and Kunitz-1. The structure reveals not only that the previously uncharacterized internal domain is a member of the polycystic kidney disease domain family but also how the two domains engage in interdomain interactions. Supported by solution small angle x-ray scattering and a combination of site-directed mutagenesis and functional assays, we show that interdomain interactions not only stabilize the fold of the internal domain but also stimulate the inhibitory activity of Kunitz-1. By completing our structural characterization of the previously unknown N-terminal region of HAI-1, we provide new insight into the interplay between tertiary structure and the inhibitory activity of a multidomain protease inhibitor. We propose a previously unseen mechanism by which the association of an auxiliary domain stimulates the inhibitory activity of a Kunitz-type inhibitor (i.e. the first structure of an intramolecular interaction between a Kunitz and another domain). PMID- 27189940 TI - Role of the JP45-Calsequestrin Complex on Calcium Entry in Slow Twitch Skeletal Muscles. AB - We exploited a variety of mouse models to assess the roles of JP45-CASQ1 (CASQ, calsequestrin) and JP45-CASQ2 on calcium entry in slow twitch muscles. In flexor digitorum brevis (FDB) fibers isolated from JP45-CASQ1-CASQ2 triple KO mice, calcium transients induced by tetanic stimulation rely on calcium entry via La(3+)- and nifedipine-sensitive calcium channels. The comparison of excitation coupled calcium entry (ECCE) between FDB fibers from WT, JP45KO, CASQ1KO, CASQ2KO, JP45-CASQ1 double KO, JP45-CASQ2 double KO, and JP45-CASQ1-CASQ2 triple KO shows that ECCE enhancement requires ablation of both CASQs and JP45. Calcium entry activated by ablation of both JP45-CASQ1 and JP45-CASQ2 complexes supports tetanic force development in slow twitch soleus muscles. In addition, we show that CASQs interact with JP45 at Ca(2+) concentrations similar to those present in the lumen of the sarcoplasmic reticulum at rest, whereas Ca(2+) concentrations similar to those present in the SR lumen after depolarization-induced calcium release cause the dissociation of JP45 from CASQs. Our results show that the complex JP45-CASQs is a negative regulator of ECCE and that tetanic force development in slow twitch muscles is supported by the dynamic interaction between JP45 and CASQs. PMID- 27189941 TI - Generation of Integration-free Induced Neural Stem Cells from Mouse Fibroblasts. AB - The viral vector-mediated overexpression of the defined transcription factors, Brn4/Pou3f4, Sox2, Klf4, and c-Myc (BSKM), could induce the direct conversion of somatic fibroblasts into induced neural stem cells (iNSCs). However, viral vectors may be randomly integrated into the host genome thereby increasing the risk for undesired genotoxicity, mutagenesis, and tumor formation. Here we describe the generation of integration-free iNSCs from mouse fibroblasts by non viral episomal vectors containing BSKM. The episomal vector-derived iNSCs (e iNSCs) closely resemble control NSCs, and iNSCs generated by retrovirus (r-iNSCs) in morphology, gene expression profile, epigenetic status, and self-renewal capacity. The e-iNSCs are functionally mature, as they could differentiate into all the neuronal cell types both in vitro and in vivo Our study provides a novel concept for generating functional iNSCs using a non-viral, non-integrating, plasmid-based system that could facilitate their biomedical applicability. PMID- 27189943 TI - Activation of the Caenorhabditis elegans Degenerin Channel by Shear Stress Requires the MEC-10 Subunit. AB - Mechanotransduction in Caenorhabditis elegans touch receptor neurons is mediated by an ion channel formed by MEC-4, MEC-10, and accessory proteins. To define the role of these subunits in the channel's response to mechanical force, we expressed degenerin channels comprising MEC-4 and MEC-10 in Xenopus oocytes and examined their response to laminar shear stress (LSS). Shear stress evoked a rapid increase in whole cell currents in oocytes expressing degenerin channels as well as channels with a MEC-4 degenerin mutation (MEC-4d), suggesting that C. elegans degenerin channels are sensitive to LSS. MEC-10 is required for a robust LSS response as the response was largely blunted in oocytes expressing homomeric MEC-4 or MEC-4d channels. We examined a series of MEC-10/MEC-4 chimeras to identify specific domains (amino terminus, first transmembrane domain, and extracellular domain) and sites (residues 130-132 and 134-137) within MEC-10 that are required for a robust response to shear stress. In addition, the LSS response was largely abolished by MEC-10 mutations encoded by a touch-insensitive mec-10 allele, providing a correlation between the channel's responses to two different mechanical forces. Our findings suggest that MEC-10 has an important role in the channel's response to mechanical forces. PMID- 27189942 TI - EHD3 Protein Is Required for Tubular Recycling Endosome Stabilization, and an Asparagine-Glutamic Acid Residue Pair within Its Eps15 Homology (EH) Domain Dictates Its Selective Binding to NPF Peptides. AB - An elaborate network of dynamic lipid membranes, termed tubular recycling endosomes (TRE), coordinates the process of endocytic recycling in mammalian cells. The C-terminal Eps15 homology domain (EHD)-containing proteins have been implicated in the bending and fission of TRE, thus regulating endocytic recycling. EHD proteins have an EH domain that interacts with proteins containing an NPF motif. We found that NPF-containing EHD1 interaction partners such as molecules interacting with CasL-like1 (MICAL-L1) and Syndapin2 are essential for TRE biogenesis. Also crucial for TRE biogenesis is the generation of phosphatidic acid, an essential lipid component of TRE that serves as a docking point for MICAL-L1 and Syndapin2. EHD1 and EHD3 have 86% amino acid identity; they homo- and heterodimerize and partially co-localize to TRE. Despite their remarkable identity, they have distinct mechanistic functions. EHD1 induces membrane vesiculation, whereas EHD3 supports TRE biogenesis and/or stabilization by an unknown mechanism. While using phospholipase D inhibitors (which block the conversion of glycerophospholipids to phosphatidic acid) to deplete cellular TRE, we observed that, upon inhibitor washout, there was a rapid and dramatic regeneration of MICAL-L1-marked TRE. Using this "synchronized" TRE biogenesis system, we determined that EHD3 is involved in the stabilization of TRE rather than in their biogenesis. Moreover, we identify the residues Ala-519/Asp-520 of EHD1 and Asn-519/Glu-520 of EHD3 as defining the selectivity of these two paralogs for NPF-containing binding partners, and we present a model to explain the atomic mechanism and provide new insight for their differential roles in vesiculation and tubulation, respectively. PMID- 27189944 TI - Molecular Basis of Membrane Association by the Phosphatidylinositol Mannosyltransferase PimA Enzyme from Mycobacteria. AB - Phosphatidyl-myo-inositol mannosyltransferase A (PimA) is an essential glycosyltransferase that initiates the biosynthetic pathway of phosphatidyl-myo inositol mannoside, lipomannan, and lipoarabinomannan, which are key glycolipids/lipoglycans of the mycobacterial cell envelope. PimA belongs to a large family of membrane-associated glycosyltransferases for which the understanding of the molecular mechanism and conformational changes that govern substrate/membrane recognition and catalysis remains a major challenge. Here, we determined that PimA preferentially binds to negatively charged phosphatidyl-myo inositol substrate and non-substrate membrane model systems (small unilamellar vesicle) through its N-terminal domain, inducing an important structural reorganization of anionic phospholipids. By using a combination of single-point mutagenesis, circular dichroism, and a variety of fluorescence spectroscopy techniques, we determined that this interaction is mainly mediated by an amphipathic alpha-helix (alpha2), which undergoes a substantial conformational change and localizes in the vicinity of the negatively charged lipid headgroups and the very first carbon atoms of the acyl chains, at the PimA-phospholipid interface. Interestingly, a flexible region within the N-terminal domain, which undergoes beta-strand-to-alpha-helix and alpha-helix-to-beta-strand transitions during catalysis, interacts with anionic phospholipids; however, the effect is markedly less pronounced to that observed for the amphipathic alpha2, likely reflecting structural plasticity/variability. Altogether, we propose a model in which conformational transitions observed in PimA might reflect a molten globule state that confers to PimA, a higher affinity toward the dynamic and highly fluctuating lipid bilayer. PMID- 27189945 TI - Mutants of Cytochrome P450 Reductase Lacking Either Gly-141 or Gly-143 Destabilize Its FMN Semiquinone. AB - NADPH-cytochrome P450 oxidoreductase transfers electrons from NADPH to cytochromes P450 via its FAD and FMN. To understand the biochemical and structural basis of electron transfer from FMN-hydroquinone to its partners, three deletion mutants in a conserved loop near the FMN were characterized. Comparison of oxidized and reduced wild type and mutant structures reveals that the basis for the air stability of the neutral blue semiquinone is protonation of the flavin N5 and strong H-bond formation with the Gly-141 carbonyl. The DeltaGly 143 protein had moderately decreased activity with cytochrome P450 and cytochrome c It formed a flexible loop, which transiently interacts with the flavin N5, resulting in the generation of both an unstable neutral blue semiquinone and hydroquinone. The DeltaGly-141 and DeltaG141/E142N mutants were inactive with cytochrome P450 but fully active in reducing cytochrome c In the DeltaGly-141 mutants, the backbone amide of Glu/Asn-142 forms an H-bond to the N5 of the oxidized flavin, which leads to formation of an unstable red anionic semiquinone with a more negative potential than the hydroquinone. The semiquinone of DeltaG141/E142N was slightly more stable than that of DeltaGly-141, consistent with its crystallographically demonstrated more rigid loop. Nonetheless, both DeltaGly-141 red semiquinones were less stable than those of the corresponding loop in cytochrome P450 BM3 and the neuronal NOS mutant (DeltaGly-810). Our results indicate that the catalytic activity of cytochrome P450 oxidoreductase is a function of the length, sequence, and flexibility of the 140s loop and illustrate the sophisticated variety of biochemical mechanisms employed in fine tuning its redox properties and function. PMID- 27189946 TI - Type II Turn of Receptor-bound Salmon Calcitonin Revealed by X-ray Crystallography. AB - Calcitonin is a peptide hormone consisting of 32 amino acid residues and the calcitonin receptor is a Class B G protein-coupled receptor (GPCR). The crystal structure of the human calcitonin receptor ectodomain (CTR ECD) in complex with a truncated analogue of salmon calcitonin ([BrPhe(22)]sCT(8-32)) has been determined to 2.1-A resolution. Parallel analysis of a series of peptide ligands showed that the rank order of binding of the CTR ECD is identical to the rank order of binding of the full-length CTR, confirming the structural integrity and relevance of the isolated CTR ECD. The structure of the CTR ECD is similar to other Class B GPCRs and the ligand binding site is similar to the binding site of the homologous receptors for the calcitonin gene-related peptide (CGRP) and adrenomedulin (AM) recently published (Booe, J. M., Walker, C. S., Barwell, J., Kuteyi, G., Simms, J., Jamaluddin, M. A., Warner, M. L., Bill, R. M., Harris, P. W., Brimble, M. A., Poyner, D. R., Hay, D. L., and Pioszak, A. A. (2015) Mol. Cell 58, 1040-1052). Interestingly the receptor-bound structure of the ligand [BrPhe(22)]sCT(8-32) differs from the receptor-bound structure of the homologous ligands CGRP and AM. They all adopt an extended conformation followed by a C terminal beta turn, however, [BrPhe(22)]sCT(8-32) adopts a type II turn (Gly(28) Thr(31)), whereas CGRP and AM adopt type I turns. Our results suggest that a type II turn is the preferred conformation of calcitonin, whereas a type I turn is the preferred conformation of peptides that require RAMPs; CGRP, AM, and amylin. In addition the structure provides a detailed molecular explanation and hypothesis regarding ligand binding properties of CTR and the amylin receptors. PMID- 27189947 TI - Structure-based Epitope Mapping of Mycobacterium tuberculosis Secretary Antigen MTC28. AB - Secretary proteins of Mycobacterium tuberculosis are key players of the mycobacterial infection pathway. MTC28 is a 28-kDa proline-rich secretary antigen of Mycobacterium tuberculosis and is only conserved in pathogenic strains of mycobacteria. Here we report the crystal structure of MTC28 at 2.8- and 2.15-A resolutions for the structure-based epitope design. MTC28 shares a "mog1p"-fold consisting of seven antiparallel beta strands stacked between alpha helices. Five probable epitopes have been located on a solvent-accessible flexible region by computational analysis of the structure of MTC28. Simultaneously, the protein is digested with trypsin and the resulting fragments are purified by HPLC. Such 10 purified peptide fragments are screened against sera from patients infected with pulmonary tuberculosis (PTB). Two of these 10 fragments, namely (127)ALDITLPMPPR(137) and (138)WTQVPDPNVPDAFVVIADR(156),are found to be major immunogenic epitopes that are localized on the outer surface of the protein molecule and are part of a single continuous epitope that have been predicted in silico Mutagenesis and antibody inhibition studies are in accordance with the results obtained from epitope mapping. PMID- 27189948 TI - Essential Role of an Unusually Long-lived Tyrosyl Radical in the Response to Red Light of the Animal-like Cryptochrome aCRY. AB - Cryptochromes constitute a group of flavin-binding blue light receptors in bacteria, fungi, plants, and insects. Recently, the response of cryptochromes to light was extended to nearly the entire visible spectral region on the basis of the activity of the animal-like cryptochrome aCRY in the green alga Chlamydomonas reinhardtii This finding was explained by the absorption of red light by the flavin neutral radical as the dark state of the receptor, which then forms the anionic fully reduced state. In this study, time-resolved UV-visible spectroscopy on the full-length aCRY revealed an unusually long-lived tyrosyl radical with a lifetime of 2.6 s, which is present already 1 MUs after red light illumination of the flavin radical. Mutational studies disclosed the tyrosine 373 close to the surface to form the long-lived radical and to be essential for photoreduction. This residue is conserved exclusively in the sequences of other putative aCRY proteins distinguishing them from conventional (6-4) photolyases. Size exclusion chromatography showed the full-length aCRY to be a dimer in the dark at 0.5 mm injected concentration with the C-terminal extension as the dimerization site. Upon illumination, partial oligomerization was observed via disulfide bridge formation at cysteine 482 in close proximity to tyrosine 373. The lack of any light response in the C-terminal extension as evidenced by FTIR spectroscopy differentiates aCRY from plant and Drosophila cryptochromes. These findings imply that aCRY might have evolved a different signaling mechanism via a light triggered redox cascade culminating in photooxidation of a yet unknown substrate or binding partner. PMID- 27189949 TI - Inadequate Reference Datasets Biased toward Short Non-epitopes Confound B-cell Epitope Prediction. AB - X-ray crystallography has shown that an antibody paratope typically binds 15-22 amino acids (aa) of an epitope, of which 2-5 randomly distributed amino acids contribute most of the binding energy. In contrast, researchers typically choose for B-cell epitope mapping short peptide antigens in antibody binding assays. Furthermore, short 6-11-aa epitopes, and in particular non-epitopes, are over represented in published B-cell epitope datasets that are commonly used for development of B-cell epitope prediction approaches from protein antigen sequences. We hypothesized that such suboptimal length peptides result in weak antibody binding and cause false-negative results. We tested the influence of peptide antigen length on antibody binding by analyzing data on more than 900 peptides used for B-cell epitope mapping of immunodominant proteins of Chlamydia spp. We demonstrate that short 7-12-aa peptides of B-cell epitopes bind antibodies poorly; thus, epitope mapping with short peptide antigens falsely classifies many B-cell epitopes as non-epitopes. We also show in published datasets of confirmed epitopes and non-epitopes a direct correlation between length of peptide antigens and antibody binding. Elimination of short, <=11-aa epitope/non-epitope sequences improved datasets for evaluation of in silico B cell epitope prediction. Achieving up to 86% accuracy, protein disorder tendency is the best indicator of B-cell epitope regions for chlamydial and published datasets. For B-cell epitope prediction, the most effective approach is plotting disorder of protein sequences with the IUPred-L scale, followed by antibody reactivity testing of 16-30-aa peptides from peak regions. This strategy overcomes the well known inaccuracy of in silico B-cell epitope prediction from primary protein sequences. PMID- 27189950 TI - Nucleoside Triphosphate Phosphohydrolase I (NPH I) Functions as a 5' to 3' Translocase in Transcription Termination of Vaccinia Early Genes. AB - Vaccinia virus early genes are transcribed immediately upon infection. Nucleoside triphosphate phosphohydrolase I (NPH I) is an essential component of the early gene transcription complex. NPH I hydrolyzes ATP to release transcripts during transcription termination. The ATPase activity of NPH I requires single-stranded (ss) DNA as a cofactor; however, the source of this cofactor within the transcription complex is not known. Based on available structures of transcription complexes it has been hypothesized that the ssDNA cofactor is obtained from the unpaired non-template strand within the transcription bubble. In vitro transcription on templates that lack portions of the non-template strand within the transcription bubble showed that the upstream portion of the transcription bubble is required for efficient NPH I-mediated transcript release. Complementarity between the template and non-template strands in this region is also required for NPH I-mediated transcript release. This observation complicates locating the source of the ssDNA cofactor within the transcription complex because removal of the non-template strand also disrupts transcription bubble reannealing. Prior studies have shown that ssRNA binds to NPH I, but it does not activate ATPase activity. Chimeric transcription templates with RNA in the non template strand confirm that the source of the ssDNA cofactor for NPH I is the upstream portion of the non-template strand in the transcription bubble. Consistent with this conclusion we also show that isolated NPH I acts as a 5' to 3' translocase on single-stranded DNA. PMID- 27189952 TI - Comparative Effectiveness of Second Vasoactive Agents in Septic Shock Refractory to Norepinephrine. AB - OBJECTIVE: We aim to identify the appropriate vasoactive agent in patients with septic shock who are refractory to optimal doses of norepinephrine. METHODS: In this retrospective observational cohort study over a 4-year period, patients who received norepinephrine within 24 hours of ICU admission and a second agent within 48 hours were enrolled. RESULTS: Among 2640 patients screened, 234 patients were enrolled, aged 60.8 +/- 17.8 years, Acute Physiology and Chronic Health Evaluation IV 98.3 +/- 27.5, 81.6% mechanically ventilated, and 65.8% in hospital mortality. Within 96 hours, 2.8 +/- 1.0 vasoactive agents were administered. Fifty, 50, 66, and 68 patients received dobutamine, dopamine, phenylephrine, and vasopressin as the second agent, with crude in-hospital mortality 40.0%, 66.0%, 74.2%, and 76.5%, respectively, P < .001. Survival analysis showed a statistically significant difference in survival time by second vasoactive agent, P < .001. After adjusting for confounding variables, dobutamine showed significant decreased odds ratio (OR) for mortality compared to vasopressin: OR 0.34 (95% confidence interval 0.14-0.84, P = .04). The relative risk of dying was 55.8% lower in patients receiving dobutamine versus vasopressin, P < .01. CONCLUSION: Dobutamine is associated with decreased mortality compared to other second vasoactive agents in septic shock when norepinephrine is not sufficient. A prospective randomized trial examining the outcome impact of the second vasoactive agent is needed. PMID- 27189951 TI - A Gene of the beta3-Glycosyltransferase Family Encodes N Acetylglucosaminyltransferase II Function in Trypanosoma brucei. AB - The bloodstream form of the human pathogen Trypanosoma brucei expresses oligomannose, paucimannose, and complex N-linked glycans, including some exceptionally large poly-N-acetyllactosamine-containing structures. Despite the presence of complex N-glycans in this organism, no homologues of the canonical N acetylglucosaminyltransferase I or II genes can be found in the T. brucei genome. These genes encode the activities that initiate the elaboration of the Manalpha1 3 and Manalpha1-6 arms, respectively, of the conserved trimannosyl-N acetylchitobiosyl core of N-linked glycans. Previously, we identified a highly divergent T. brucei N-acetylglucosaminyltransferase I (TbGnTI) among a set of putative T. brucei glycosyltransferase genes belonging to the beta3 glycosyltransferase superfamily (Damerow, M., Rodrigues, J. A., Wu, D., Guther, M. L., Mehlert, A., and Ferguson, M. A. (2014) J. Biol. Chem. 289, 9328-9339). Here, we demonstrate that TbGT15, another member of the same beta3 glycosyltransferase family, encodes an equally divergent N acetylglucosaminyltransferase II (TbGnTII) activity. In contrast to multicellular organisms, where GnTII activity is essential, TbGnTII null mutants of T. brucei grow in culture and are still infectious to animals. Characterization of the large poly-N-acetyllactosamine containing N-glycans of the TbGnTII null mutants by methylation linkage analysis suggests that, in wild-type parasites, the Manalpha1-6 arm of the conserved trimannosyl core may carry predominantly linear poly-N-acetyllactosamine chains, whereas the Manalpha1-3 arm may carry predominantly branched poly-N-acetyllactosamine chains. These results provide further detail on the structure and biosynthesis of complex N-glycans in an important human pathogen and provide a second example of the adaptation by trypanosomes of beta3-glycosyltransferase family members to catalyze beta1-2 glycosidic linkages. PMID- 27189953 TI - Fluconazole-induced long QT syndrome via impaired human ether-a-go-go-related gene (hERG) protein trafficking in rabbits. AB - Aims: hERG protein trafficking deficiency has long been known in drug-induced long QT syndrome (LQTS). However, validated evidence from in vivo data kept scanty. Our goal was to investigate the proarrhythmic action of fluconazole and its underlying mechanism in an animal model. Methods and results: Twenty female Japanese long-eared white rabbits were randomly distributed into a control group and a fluconazole group for a chronic 2-week treatment. The control group was treated with 0.5% sodium carboxymethylcellulose (CMCNa), and the fluconazole group was treated with fluconazole. Electrocardiograms (ECGs) were recorded during the experimental period. Isolated arterially perfused left ventricular wedge preparations from the rabbits were made 2 weeks after treatment, and the arrhythmia events, the transmural ECG, and action potential from both the endocardium and epicardium were recorded. The changes in hERG protein expression were measured by western blot. The fluconazole group showed a longer QT interval 1 week after treatment (P < 0.05) and a higher arrhythmia occurrence 2 weeks after treatment (P < 0.05) than the control group. The fluconazole group also showed a longer transmural dispersion of repolarization and a higher occurrence of life-threatening torsades de pointes in arterially perfused left ventricular preparations. Furthermore, western blot analysis showed that the density of mature hERG protein was lower in the fluconazole group than that in the control group. Conclusion: Fluconazole can prolong the QT interval and possess proarrhythmic activity due to its inhibition of hERG protein trafficking in our experimental model. These findings may impact the clinical potential of fluconazole in humans. PMID- 27189956 TI - Solvent-facilitated lead disconnection for battery replacement in patients with pacemakers or implantable cardioverter defibrillators. AB - AIMS: Battery exchange in pacemaker (PM) or implantable cardioverter defibrillator (ICD) devices may be occasionally problematic because of difficulties in lead disconnection procedures and risk of injuring the fragile leads. This pilot study compares ethanol and dimethyl sulfoxide (DMSO) as solvents to assist removal of leads from PM or ICD device headers in cases of stuck leads or difficulties in untightening device header screws. METHODS AND RESULTS: Of the total number (527) of our patients requiring battery replacement due to end-of-life (EOL) warnings, conventional exchange was not possible in 34 (6.5%) due to embedding of the lead within blood-derived material. Of these, 30 (17 with PM, 13 with ICD) consented to the study and were randomly assigned to a primary attempt at lead disconnection by ethanol (n = 17) or by DMSO (n = 13). If the primary attempt failed, a secondary attempt at lead disconnection was undertaken using the alternate solvent. Ethanol was a superior solvent compared with DMSO, yielding successful disconnection at primary attempt in 88.2% (15/17) vs. 23.1% (3/13) of cases. In 8 patients in whom the primary DMSO-attempted disconnection failed, a secondary attempt with ethanol yielded success in 6 (75%) cases. Use of either ethanol or DMSO in lead disconnection was not associated with any adverse events or effects. CONCLUSION: Ethanol has utility as a simple and inexpensive modality for lead disconnection from ICD or PM headers. PMID- 27189954 TI - Multipoint pacing via a quadripolar left-ventricular lead: preliminary results from the Italian registry on multipoint left-ventricular pacing in cardiac resynchronization therapy (IRON-MPP). AB - Aims: This registry was created to describe the experience of 76 Italian centres with a large cohort of recipients of multipoint pacing (MPP) capable cardiac resynchronization therapy (CRT) devices. Methods and results: A total of 507 patients in whom these devices had been successfully implanted were enrolled between August 2013 and May 2015. We analysed: (i) current clinical practices for the management of such patients, and (ii) the impact of MPP on heart failure clinical composite response and on the absolute change in ejection fraction (EF) at 6 months. Multipoint pacing was programmed to 'ON' in 46% of patients before discharge. Methods of optimizing MPP programming were most commonly based on either the greatest narrowing of the QRS complex (38%) or the electrical delays between the electrodes (34%). Clinical and echocardiographic follow-up data were evaluated in 232 patients. These patients were divided into two groups according to whether MPP was programmed to 'ON' (n = 94) or 'OFF' (n = 138) at the time of discharge. At 6 months, EF was significantly higher in the MPP group than in the biventricular-pacing group (39.1 +/- 9.6 vs. 34.7 +/- 7.6%; P < 0.001). Even after adjustments, early MPP activation remained an independent predictor of absolute increase in LVEF of >=5% (odds ratio 2.5; P = 0.001). At 6 months, an improvement in clinical composite score was recorded in a greater proportion of patients with MPP-ON than in controls (56 vs. 38%; P = 0.009). On comparing optimal MPP and conventional vectors, QRS was also seen to have decreased significantly (P < 0.001). Conclusion: This study provides information that is essential in order to deal with the expected increase in the number of patients receiving MPP devices in the coming years. The results revealed different practices among centres, and establishing the optimal programming that can maximize the benefit of MPP remains a challenging issue. Compared with conventional CRT, MPP improved clinical status and resulted in an additional increase in EF. Clinical Trial Registration: http://www.clinicaltrial.gov/. Unique identifier: NCT02606071. PMID- 27189957 TI - Serotonin synthesis rate and the tryptophan hydroxylase-2: G-703T polymorphism in social anxiety disorder. AB - It is disputed whether anxiety disorders, like social anxiety disorder, are characterized by serotonin over- or underactivity. Here, we evaluated whether our recent finding of elevated neural serotonin synthesis rate in patients with social anxiety disorder could be reproduced in a separate cohort, and whether allelic variation in the tryptophan hydroxylase-2 (TPH2) G-703T polymorphism relates to differences in serotonin synthesis assessed with positron emission tomography. Eighteen social anxiety disorder patients and six healthy controls were scanned during 60 minutes in a resting state using positron emission tomography and 5-hydroxy-L-[beta -(11)C]tryptophan, [(11)C]5-HTP, a substrate of the second enzymatic step in serotonin synthesis. Parametric images were generated, using the reference Patlak method, and analysed using Statistical Parametric Mapping (SPM8). Blood samples for genotyping of the TPH2 G-703T polymorphism were obtained from 16 social anxiety disorder patients (T carriers: n=5, GG carriers: n=11). A significantly elevated [(11)C]5-HTP accumulation rate, indicative of enhanced decarboxylase activity and thereby serotonin synthesis capacity, was detected in social anxiety disorder patients compared with controls in the hippocampus and basal ganglia nuclei and, at a more lenient (uncorrected) statistical threshold, in the amygdala and anterior cingulate cortex. In patients, the serotonin synthesis rate in the amygdala and anterior cingulate cortex was significantly elevated in TPH2 T carriers in comparison with GG homozygotes. Our results support that social anxiety disorder entails an overactive presynaptic serotonergic system that, in turn, seems functionally influenced by the TPH2 G-703T polymorphism in emotionally relevant brain regions. PMID- 27189959 TI - Ethics, aesthetics and euphemism: the vulva in contemporary society. PMID- 27189958 TI - Helicobacter pylori vacA transcription is genetically-determined and stratifies the level of human gastric inflammation and atrophy. AB - AIMS: Helicobacter pylori infection is the major cause of peptic ulceration and gastric cancer, and an important virulence determinant is its vacuolating cytotoxin vacA. Previously, we have described allelic variation in vacA which determines toxin activity and disease risk. Here we aimed to quantify vacA mRNA expression in the human stomach, define its genetic determinants and assess how well it predicts gastric pathology. METHODS: Gastric biopsies were donated by 39 patients with H. pylori infection attending for endoscopy at Queen's Medical Centre, Nottingham, UK. Total RNA was extracted, and vacA mRNA quantified by reverse transcriptase quantitative PCR. Separate biopsies were histologically scored for inflammation and atrophy using the updated Sydney system. H. pylori strains were isolated from further biopsies, and the nucleotide sequence upstream of vacA determined. RESULTS: vacA mRNA levels in human stomachs varied by two orders of magnitude independently of vacA allelic type. Among vacA i1-type (toxic) strains, increased vacA expression was strongly associated with higher grade gastric inflammation (p<0.02), neutrophil infiltration (p<0.005) and the presence of atrophy (p<0.01). A polymorphism at nucleotide +28 near the base of a potential stem-loop structure within the 5' untranslated region was significantly associated with vacA transcript level and inflammation. CONCLUSIONS: Increased gastric vacA expression during H. pylori infection is associated with inflammation and premalignant pathology. The +28 nucleotide within the vacA 5' stem-loop stratifies disease risk among toxic vacA i1-type strains. PMID- 27189960 TI - The Rapidly Acting Antidepressant Ketamine and the mGlu2/3 Receptor Antagonist LY341495 Rapidly Engage Dopaminergic Mood Circuits. AB - Ketamine is a rapidly acting antidepressant in patients with treatment-resistant depression (TRD). Although the mechanisms underlying these effects are not fully established, inquiry to date has focused on the triggering of synaptogenesis transduction pathways via glutamatergic mechanisms. Preclinical data suggest that blockade of metabotropic glutamate (mGlu2/3) receptors shares many overlapping features and mechanisms with ketamine and may also provide rapid efficacy for TRD patients. Central dopamine circuitry is recognized as an end target for mood regulation and hedonic valuation and yet has been largely neglected in mechanistic studies of antidepressant-relevant effects of ketamine. Herein, we evaluated the changes in dopaminergic neurotransmission after acute administration of ketamine and the mGlu2/3 receptor antagonist LY341495 [(2S)-2 amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid ] in preclinical models using electrophysiologic, neurochemical, and behavioral endpoints. When given acutely, both ketamine and LY341495, but not the selective serotonin reuptake inhibitor (SSRI) citalopram, increased the number of spontaneously active dopamine neurons in the ventral tegmental area (VTA), increased extracellular levels of dopamine in the nucleus accumbens and prefrontal cortex, and enhanced the locomotor stimulatory effects of the dopamine D2/3 receptor agonist quinpirole. Further, both ketamine and LY341495 reduced immobility time in the tail-suspension assay in CD1 mice, which are relatively resistant to SSRI antidepressants. Both the VTA neuronal activation and the antidepressant phenotype induced by ketamine and LY341495 were attenuated by the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo- (9CI)-benzo[f]quinoxaline-7 sulfonamide, indicating AMPA-dependent effects. These findings provide another overlapping mechanism of action of ketamine and mGlu2/3 receptor antagonism that differentiates them from conventional antidepressants and thus support the potential rapidly acting antidepressant actions of mGlu2/3 receptor antagonism in patients. PMID- 27189964 TI - Endogenous 5-HT2C Receptors Phosphorylate the cAMP Response Element Binding Protein via Protein Kinase C-Promoted Activation of Extracellular-Regulated Kinases-1/2 in Hypothalamic mHypoA-2/10 Cells. AB - Serotonin 5-HT2C receptors (5-HT2CR) activate Gq proteins and are expressed in the central nervous system (CNS). 5-HT2CR regulate emotion, feeding, reward, or cognition and may serve as promising drug targets to treat psychiatric disorders or obesity. Owing to technical difficulties in isolating cells from the CNS and the lack of suitable cell lines endogenously expressing 5-HT2CR, our knowledge about this receptor subtype in native environments is rather limited. The hypothalamic mHypoA-2/10 cell line was recently established and resembles appetite-regulating hypothalamic neurons of the paraventricular nucleus (PVN), where 5-HT2CR have been detected in vivo. Therefore, we tested mHypoA-2/10 cells for endogenous 5-HT2CR expression. Serotonin or the 5-HT2CR preferential agonist WAY-161,503 initiated cAMP response element (CRE)-dependent gene transcription with EC50 values of 15.5 +/- 9.8 and 1.1 +/- 0.9 nM, respectively. Both responses were blocked by two unrelated 5-HT2CR-selective antagonists (SB-242,084, RS 102,221) but not by a 5-HT2AR (EMD-281,014) or 5-HT2BR (RS-127,455) antagonists. By single-cell calcium imaging, we found that serotonin and WAY-161,503 induced robust calcium transients, which were also blunted by both 5-HT2CR antagonists. Additionally we revealed, first, that 5-HT2CR induced CRE activation via protein kinase C (PKC)-mediated engagement of extracellular-regulated kinases-1/2 and, second, that intrinsic activity of WAY-161,503 was in the range of 0.3-0.5 compared with serotonin, defining the frequently used 5-HT2CR agonist as a partial agonist of endogenous 5-HT2CR. In conclusion, we have shown that hypothalamic mHypoA-2/10 cells endogenously express 5-HT2CR and thus are the first cell line in which to analyze 5-HT2CR pharmacology, signaling, and regulation in its natural environment. PMID- 27189961 TI - Reactive Oxygen Species Differentially Regulate Bone Turnover in an Age-Specific Manner in Catalase Transgenic Female Mice. AB - Chronic ethyl alcohol (EtOH) consumption results in reactive oxygen species (ROS) generation in bone and osteopenia due to increased bone resorption and reduced bone formation. In this study, transgenic C57Bl/6J mice overexpressing human catalase (TgCAT) were used to test whether limiting excess hydrogen peroxide would protect against EtOH-mediated bone loss. Micro-computed tomography analysis of the skeletons of 6-week-old female chow-fed TgCAT mice revealed a high bone mass phenotype with increased cortical bone area and thickness as well as significantly increased trabecular bone volume (P < 0.05). Six-week-old wild-type (WT) and TgCAT female mice were chow fed or pair fed (PF) liquid diets with or without EtOH, approximately 30% of calories, for 8 weeks. Pair feeding of WT had no demonstrable effect on the skeleton; however, EtOH feeding of WT mice significantly reduced cortical and trabecular bone parameters along with bone strength compared with PF controls (P < 0.05). In contrast, EtOH feeding of TgCAT mice had no effect on trabecular bone compared with PF controls. At 14 weeks of age, there was significantly less trabecular bone and cortical cross-sectional area in TgCAT mice than WT mice (P < 0.05), suggesting impaired normal bone accrual with age. TgCAT mice expressed less collagen1alpha and higher sclerostin mRNA (P < 0.05), suggesting decreased bone formation in TgCAT mice. In conclusion, catalase overexpression resulted in greater bone mass than in WT mice at 6 weeks and lower bone mass at 14 weeks. EtOH feeding induced significant reductions in bone architecture and strength in WT mice, but TgCAT mice were partially protected. These data implicate ROS signaling in the regulation of bone turnover in an age-dependent manner, and indicate that excess hydrogen peroxide generation contributes to alcohol-induced osteopenia. PMID- 27189963 TI - Physiological Content and Intrinsic Activities of 10 Cytochrome P450 Isoforms in Human Normal Liver Microsomes. AB - Due to a lack of physiologic cytochrome P450 (P450) isoform content, P450 activity is typically only determined at the microsomal level (per milligram of microsomal protein) and not at the isoform level (per picomole of P450 isoform), which could result in the misunderstanding of variations in P450 activity between individuals and further hinder development of personalized medicine. We found that there were large variations in protein content, mRNA levels, and intrinsic activities of the 10 P450s in 100 human liver samples, in which CYP2E1 and CYP2C9 showed the highest expression levels. P450 gene polymorphisms had different effects on activity at two levels: CYP3A5*3 and CYP2A6*9 alleles conferred increased activity at the isoform level but decreased activity at the microsomal level; CYP2C9*3 had no effect at the isoform level but decreased activity at the microsomal level. The different effects at each level stem from the different effects of each polymorphism on the resulting P450 protein. Individuals with CYP2A6*1/*4, CYP2A6*1/*9, CYP2C9*1/*3, CYP2D6 100C>T TT, CYP2E1 7632T>A AA, CYP3A5*1*3, and CYP3A5*3*3 genotypes had significantly lower protein content, whereas CYP2D6 1661G>C mutants had a higher protein content. In conclusion, we first offered the physiologic data of 10 P450 isoform contents and found that some single nucleotide polymorphisms had obvious effects on P450 expression in human normal livers. The effects of gene polymorphisms on intrinsic P450 activity at the isoform level were quite different from those at the microsomal level, which might be due to changes in P450 protein content. PMID- 27189962 TI - Nuclear Factor Erythroid 2-Related Factor 2 Deficiency Results in Amplification of the Liver Fat-Lowering Effect of Estrogen. AB - Transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) regulates multiple biologic processes, including hepatic lipid metabolism. Estrogen exerts actions affecting energy homeostasis, including a liver fat-lowering effect. Increasing evidence indicates the crosstalk between these two molecules. The aim of this study was to evaluate whether Nrf2 modulates estrogen signaling in hepatic lipid metabolism. Nonalcoholic fatty liver disease (NAFLD) was induced in wild-type and Nrf2-null mice fed a high-fat diet and the liver fat-lowering effect of exogenous estrogen was subsequently assessed. We found that exogenous estrogen eliminated 49% and 90% of hepatic triglycerides in wild-type and Nrf2 null mice with NAFLD, respectively. This observation demonstrates that Nrf2 signaling is antagonistic to estrogen signaling in hepatic fat metabolism; thus, Nrf2 absence results in striking amplification of the liver fat-lowering effect of estrogen. In addition, we found the association of trefoil factor 3 and fatty acid binding protein 5 with the liver fat-lowering effect of estrogen. In summary, we identified Nrf2 as a novel and potent inhibitor of estrogen signaling in hepatic lipid metabolism. Our finding may provide a potential strategy to treat NAFLD by dually targeting Nrf2 and estrogen signaling. PMID- 27189965 TI - Ethanol Tolerance Affects Endogenous Adenosine Signaling in Mouse Hippocampus. AB - Ethanol has many pharmacological effects, including increases in endogenous adenosine levels and adenosine receptor activity in brain. Ethanol consumption is associated with both positive and negative health outcomes, but tolerance to the behavioral effects of ethanol can lead to increased consumption, which increases the risk of negative health outcomes. The present study was performed to test whether a 7-day treatment with ethanol is linked to reduced adenosine signaling and whether this is a consequence of reduced ecto-5'-nucleotidase activity. Wild type (CD73(+/+)) and ecto-5'-nucleotidase-deficient (CD73(-/-)) mice were treated with ethanol (2 g/kg) or saline for 7 days. In CD73(+/+) mice, repeated ethanol treatment reduced the hypothermic and ataxic effects of acute ethanol, indicating the development of tolerance to the acute effects of ethanol. In CD73(+/+) mice, this 7-day ethanol treatment led to increased hippocampal synaptic activity and reduced adenosine A1 receptor activity under both basal and low Mg(2+) conditions. These effects of ethanol tolerance were associated with an 18% decrease in activity of ecto-5'-nucleotidase activity in hippocampal cell membranes. In contrast, ethanol treatment was not associated with changes in synaptic activity or adenosine signaling in hippocampus from CD73(-/-) mice. These data indicate that ethanol treatment is associated with a reduction in adenosine signaling through adenosine A1 receptors in hippocampus, mediated, at least in part, via reduced ecto-5'-nucleotidase activity. PMID- 27189968 TI - New Insight into the Dietary Cause of Atherosclerosis: Implications for Pharmacology. AB - At present, the guideline approach to the medical treatment and prevention of atherosclerotic cardiovascular disease (ASCVD) is to classify patients by risk and treat the known risk factors (contributory causes), e.g., hypertension, diabetes, obesity, smoking, and poor diet, as appropriate. All high-risk patients should receive statins. This approach has had substantial success but ASCVD still remains the number one cause of death in the United States. Until recently, the underlying cause of ASCVD remained unknown, although a potential dietary cause was suggested by the fact that vegetarians, especially vegans, have a much lower incidence of ASCVD than animal flesh eaters. Recently, consistent with the vegetarian data, substantial evidence for a cause of ASCVD in animals and humans has been discovered. Trimethylamine (TMA)-containing dietary compounds in meat, milk, and other animal foods (e.g., lecithin, choline, and carnitine) are converted by closely related gut bacterial TMA lyases to TMA, which is absorbed and converted predominantly by flavin mono-oxygenase 3 to the toxic trimethylamine N-oxide (TMAO). TMAO causes atherosclerosis in animals and is elevated in patients with coronary heart disease. Inhibition of bacterial lyases in mice prevents TMA and secondarily TMAO formation and atherosclerosis, strong evidence for the TMAO hypothesis. At present, the challenge for the pharmaceutical industry is to discover and develop a potent "broad spectrum" bacterial lyase inhibitor that, along with diet and exercise, could, if the TMAO hypothesis is correct, revolutionize the preventive treatment of ASCVD. PMID- 27189966 TI - Protective Action of Anandamide and Its COX-2 Metabolite against l-Homocysteine Induced NLRP3 Inflammasome Activation and Injury in Podocytes. AB - Recent studies have demonstrated that l-homocysteine (Hcys)-induced podocyte injury leading to glomerular damage or sclerosis is attributable to the activation of the nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome. Given the demonstrated anti inflammatory effects of endocannabinoids, the present study was designed to test whether anandamide (AEA) or its metabolites diminish NLRP3 inflammasome activation and prevent podocyte injury and associated glomerular damage during hyperhomocysteinemia (hHcys). AEA (100 MUM) inhibited Hcys-induced NLRP3 inflammasome activation in cultured podocytes, as indicated by elevated caspase-1 activity and interleukin-1beta levels, and attenuated podocyte dysfunction, as shown by reduced vascular endothelial growth factor production. These effects of AEA were inhibited by the cyclooxygenase-2 (COX-2) inhibitor celecoxib (CEL). In mice in vivo, AEA treatment attenuated glomerular NLRP3 inflammasome activation induced by hHcys accompanying a folate-free diet, on the basis of inhibition of hHcys-induced colocalization of NLRP3 molecules and increased interleukin-1beta levels in glomeruli. Correspondingly, AEA prevented hHcys-induced proteinuria, albuminuria, and glomerular damage observed microscopically. Hcys- and AEA induced effects were absent in NLRP3-knockout mice. These beneficial effects of AEA against hHcys-induced NLRP3 inflammasome activation and glomerular injury were not observed in mice cotreated with CEL. We further demonstrated that prostaglandin E2-ethanolamide (PGE2-EA), a COX-2 product of AEA, at 10 MUM had a similar inhibitory effect to that of 100 MUM AEA on Hcys-induced NLRP3 inflammasome formation and activation in cultured podocytes. From these results, we conclude that AEA has anti-inflammatory properties, protecting podocytes from Hcys-induced injury by inhibition of NLRP3 inflammasome activation through its COX-2 metabolite, PGE2-EA. PMID- 27189967 TI - Preferential Delivery of an Opioid Antagonist to the Fetal Brain in Pregnant Mice. AB - Prolonged fetal exposure to opioids results in neonatal abstinence syndrome (NAS), a major medical problem requiring intensive care and increased hospitalization times for newborns with NAS. Multiple strategies are currently available to alleviate withdrawal in infants with NAS. To prevent NAS caused by opioid maintenance programs in pregnant women, blocking fetal dependence without compromising the mother's opiate therapy is desirable. Here we tested in pregnant mice whether a peripherally selective opioid antagonist can preferentially enter the fetal brain and, thereby, in principle, selectively protect the fetus. We show using mass spectrometry that 6beta-naltrexol, a neutral opioid antagonist with very limited ability to cross the blood-brain barrier (BBB), readily crosses the placental barrier and enters the fetal brain at high levels, although it is relatively excluded from the maternal brain. Furthermore, owing to the late development of the BBB in postnatal mice, we show that 6beta-naltrexol can readily enter the juvenile mouse brain until at least postnatal day 14. Taking advantage of this observation, we show that long-term exposure to morphine starting in the second postnatal week causes robust and quantifiable dependence behaviors that are suppressed by concomitant administration of 6beta-naltrexol with much greater potency (ID50 0.022-0.044 mg/kg, or 1/500 the applied dose of morphine) than previously demonstrated for either the suppression of central nervous system opioid effects or the induction of withdrawal in adults. These results indicate that peripherally selective opioid antagonists capable of penetrating the placenta may be beneficial for preventing or reducing neonatal dependence and NAS in a dose range that should not interfere with maternal opioid maintenance. PMID- 27189969 TI - Berberine Decreased Inducible Nitric Oxide Synthase mRNA Stability through Negative Regulation of Human Antigen R in Lipopolysaccharide-Induced Macrophages. AB - Berberine, a major isoquinoline alkaloid found in medicinal herbs, has been reported to possess anti-inflammatory effects; however, the underlying mechanisms responsible for its actions are poorly understood. In the present study, we investigated the inhibitory effects of berberine and the molecular mechanisms involved in lipopolysaccharide (LPS)-treated RAW 264.7 and THP-1 macrophages and its effects in LPS-induced septic shock in mice. In both macrophage cell types, berberine inhibited the LPS-induced nitric oxide (NO) production and inducible NO synthase (iNOS) protein expression, but it had no effect on iNOS mRNA transcription. Suppression of LPS-induced iNOS protein expression by berberine occurred via a human antigen R (HuR)-mediated reduction of iNOS mRNA stability. Molecular data revealed that the suppression on the LPS-induced HuR binding to iNOS mRNA by berberine was accompanied by a reduction in nucleocytoplasmic HuR shuttling. Pretreatment with berberine reduced LPS-induced iNOS protein expression and the cytoplasmic translocation of HuR in liver tissues and increased the survival rate of mice with LPS-induced endotoxemia. These results show that the suppression of iNOS protein expression by berberine under LPS induced inflammatory conditions is associated with a reduction in iNOS mRNA stability resulting from inhibition of the cytoplasmic translocation of HuR. PMID- 27189970 TI - Blockade of Cocaine or sigma Receptor Agonist Self Administration by Subtype Selective sigma Receptor Antagonists. AB - The identification of sigma receptor (sigmaR) subtypes has been based on radioligand binding and, despite progress with sigma1R cellular function, less is known about sigmaR subtype functions in vivo. Recent findings that cocaine self administration experience will trigger sigmaR agonist self administration was used in this study to assess the in vivo receptor subtype specificity of the agonists (+)-pentazocine, PRE-084 [2-(4-morpholinethyl) 1 phenylcyclohexanecarboxylate hydrochloride], and 1,3-di-o-tolylguanidine (DTG) and several novel putative sigmaR antagonists. Radioligand binding studies determined in vitro sigmaR selectivity of the novel compounds, which were subsequently studied for self administration and antagonism of cocaine, (+) pentazocine, PRE-084, or DTG self administration. Across the dose ranges studied, none of the novel compounds were self administered, nor did they alter cocaine self administration. All compounds blocked DTG self administration, with a subset also blocking (+)-pentazocine and PRE-084 self administration. The most selective of the compounds in binding sigma1Rs blocked cocaine self administration when combined with a dopamine transport inhibitor, either methylphenidate or nomifensine. These drug combinations did not decrease rates of responding maintained by food reinforcement. In contrast, the most selective of the compounds in binding sigma2Rs had no effect on cocaine self administration in combination with either dopamine transport inhibitor. Thus, these results identify subtype-specific in vivo antagonists, and the utility of sigmaR agonist substitution for cocaine self administration as an assay capable of distinguishing sigmaR subtype selectivity in vivo. These results further suggest that effectiveness of dual sigmaR antagonism and dopamine transport inhibition in blocking cocaine self administration is specific for sigma1Rs and further support this dual targeting approach to development of cocaine antagonists. PMID- 27189971 TI - Vascular and Central Activation of Peroxisome Proliferator-Activated Receptor beta Attenuates Angiotensin II-Induced Hypertension: Role of RGS-5. AB - Activation of peroxisome proliferator-activated receptor-beta/delta (PPARbeta) lowers blood pressure in genetic and mineralocorticoid-induced hypertension. Regulator of G-protein-coupled receptor signaling 5 (RGS5) protein, which interferes in angiotensin II (AngII) signaling, is a target gene to PPARbeta The aim of the present study was to examine whether PPARbeta activation in resistance arteries and brain tissues prevents the elevated blood pressure in AngII-induced hypertension and evaluate the role of RGS5 in this effect. C57BL/6J male mice were divided into five groups (control mice, PPARbeta agonist [4-[[[2-[3-Fluoro-4 (trifluoromethyl)phenyl]-4-methyl-5-thiazolyl]methyl]thio]-2-methylphenoxy]acetic acid (GW0742)-treated mice AngII-infused mice, GW0742-treated AngII-infused mice, and AngII-infused mice treated with GW0742 plus PPARbeta antagonist 3-[[[2 Methoxy-4-(phenylamino)phenyl]amino]sulfonyl]-2-thiophenecarboxylic acid methyl ester (GSK0660)) and were followed for 3 weeks. GW0742 prevented the increase in both arterial blood pressure and plasma noradrenaline levels and the higher reduction of blood pressure after ganglionic blockade, whereas it reduced the mesenteric arterial remodeling and the hyper-responsiveness to vasoconstrictors (AngII and endothelin-1) in AngII-infused mice. These effects were accompanied by an inhibition of NADPH oxidase expression and activity in the brain. Gene expression profiling revealed a marked loss of brainstem and vascular RGS5 in AngII-infused mice, which was restored by GW0742. GW0742-induced effects were abolished by GSK0660. Small interfering RNA targeting RGS5 caused augmented contractile response to AngII in resistance mesenteric arteries and blunted the inhibitory effect of GW0742 on this response. In conclusion, GW0742 exerted antihypertensive effects, restoring sympathetic tone and vascular structure and function in AngII-infused mice by PPARbeta activation in brain and vessels inhibiting AngII signaling as a result of RGS5 upregulation. PMID- 27189972 TI - Interaction of the Sodium/Glucose Cotransporter (SGLT) 2 inhibitor Canagliflozin with SGLT1 and SGLT2. AB - Canagliflozin, a selective sodium/glucose cotransporter (SGLT) 2 inhibitor, suppresses the renal reabsorption of glucose and decreases blood glucose level in patients with type 2 diabetes. A characteristic of canagliflozin is its modest SGLT1 inhibitory action in the intestine at clinical dosage. To reveal its mechanism of action, we investigated the interaction of canagliflozin with SGLT1 and SGLT2. Inhibition kinetics and transporter-mediated uptake were examined in human SGLT1- or SGLT2-expressing cells. Whole-cell patch-clamp recording was conducted to examine the sidedness of drug action. Canagliflozin competitively inhibited SGLT1 and SGLT2, with high potency and selectivity for SGLT2. Inhibition constant (Ki) values for SGLT1 and SGLT2 were 770.5 and 4.0 nM, respectively. (14)C-canagliflozin was suggested to be transported by SGLT2; however, the transport rate was less than that of alpha-methyl-d-glucopyranoside. Canagliflozin inhibited alpha-methyl-d-glucopyranoside-induced SGLT1- and SGLT2 mediated inward currents preferentially from the extracellular side and not from the intracellular side. Based on the Ki value, canagliflozin is estimated to sufficiently inhibit SGLT2 from the urinary side in renal proximal tubules. The Ki value for SGLT1 suggests that canagliflozin suppresses SGLT1 in the small intestine from the luminal side, whereas it does not affect SGLT1 in the heart and skeletal muscle, considering the maximal concentration of plasma-unbound canagliflozin. Similarly, SGLT1 in the kidney would not be inhibited, thereby aiding in the prevention of hypoglycemia. After binding to SGLT2, canagliflozin may be reabsorbed by SGLT2, which leads to the low urinary excretion and prolonged drug action of canagliflozin. PMID- 27189973 TI - The gamma-Secretase Modulator, BMS-932481, Modulates Abeta Peptides in the Plasma and Cerebrospinal Fluid of Healthy Volunteers. AB - The pharmacokinetics, pharmacodynamics, safety, and tolerability of BMS-932481, a gamma-secretase modulator (GSM), were tested in healthy young and elderly volunteers after single and multiple doses. BMS-932481 was orally absorbed, showed dose proportionality after a single dose administration, and had approximately 3-fold accumulation after multiple dosing. High-fat/caloric meals doubled the Cmax and area under the curve and prolonged Tmax by 1.5 hours. Consistent with the preclinical pharmacology of GSMs, BMS-932481 decreased cerebrospinal fluid (CSF) Abeta39, Abeta40, and Abeta42 while increasing Abeta37 and Abeta38, thereby providing evidence of gamma-secretase enzyme modulation rather than inhibition. In plasma, reductions in Abeta40 and Abeta42 were observed with no change in total Abeta; in CSF, modest decreases in total Abeta were observed at higher dose levels. Increases in liver enzymes were observed at exposures associated with greater than 70% CSF Abeta42 lowering after multiple dosing. Although further development was halted due to an insufficient safety margin to test the hypothesis for efficacy of Abeta lowering in Alzheimer's disease, this study demonstrates that gamma-secretase modulation is achievable in healthy human volunteers and supports further efforts to discover well tolerated GSMs for testing in Alzheimer's disease and other indications. PMID- 27189975 TI - The costs of inequality: whole-population modelling study of lifetime inpatient hospital costs in the English National Health Service by level of neighbourhood deprivation. AB - BACKGROUND: There are substantial socioeconomic inequalities in both life expectancy and healthcare use in England. In this study, we describe how these two sets of inequalities interact by estimating the social gradient in hospital costs across the life course. METHODS: Hospital episode statistics, population and index of multiple deprivation data were combined at lower-layer super output area level to estimate inpatient hospital costs for 2011/2012 by age, sex and deprivation quintile. Survival curves were estimated for each of the deprivation groups and used to estimate expected annual costs and cumulative lifetime costs. RESULTS: A steep social gradient was observed in overall inpatient hospital admissions, with rates ranging from 31 298/100 000 population in the most affluent fifth of areas to 43 385 in the most deprived fifth. This gradient was steeper for emergency than for elective admissions. The total cost associated with this inequality in 2011/2012 was L4.8 billion. A social gradient was also observed in the modelled lifetime costs where the lower life expectancy was not sufficient to outweigh the higher average costs in the more deprived populations. Lifetime costs for women were 14% greater than for men, due to higher costs in the reproductive years and greater life expectancy. CONCLUSIONS: Socioeconomic inequalities result in increased morbidity and decreased life expectancy. Interventions to reduce inequality and improve health in more deprived neighbourhoods have the potential to save money for health systems not only within years but across peoples' entire lifetimes, despite increased costs due to longer life expectancies. PMID- 27189976 TI - Socioeconomic inequalities in a 16-year longitudinal measurement of successful ageing. AB - BACKGROUND: This study examines to what extent education, occupation and income are associated with the multidimensional process of successful ageing, encompassing trajectories of physical, mental and social functioning in old age. METHODS: We employed 16-year longitudinal data from 2095 participants aged 55-85 years at baseline in the Dutch, nationally representative Longitudinal Aging Study Amsterdam. For 9 indicators of successful ageing, separate Latent Class Growth models were used to identify subgroups of older adults with a 'successful' trajectory. A 'Successful Aging Index' expressed the number of indicators for which individual respondents had a successful trajectory (range 0-9). Using multivariate regression models, we investigated associations between socioeconomic position and the Successful Ageing Index, and with separate indicators of successful ageing. RESULTS: Higher education, occupational skill level and income were independently associated with higher numbers of successful trajectories. Education (beta=0.09) was a slightly stronger correlate of successful ageing than income (beta=0.08). Analyses of separate indicators of successful ageing showed that cognitive functioning, functional limitations and emotional support given were associated with all three components of socioeconomic position, while other indicators were associated with only one (eg, life satisfaction) or none (eg, social loneliness). For some indicators of successful ageing, socioeconomic inequalities were present at baseline, and also increased or decreased during follow-up. CONCLUSIONS: Education, occupation and income represent distinct socioeconomic life course factors, each of which contribute in a specific way to inequalities in successful ageing. Physical and cognitive functioning were associated more strongly with socioeconomic position than social and emotional functioning. PMID- 27189974 TI - Robust Translation of gamma-Secretase Modulator Pharmacology across Preclinical Species and Human Subjects. AB - The amyloid-beta peptide (Abeta)-in particular, the 42-amino acid form, Abeta1-42 is thought to play a key role in the pathogenesis of Alzheimer's disease (AD). Thus, several therapeutic modalities aiming to inhibit Abeta synthesis or increase the clearance of Abeta have entered clinical trials, including gamma secretase inhibitors, anti-Abeta antibodies, and amyloid-beta precursor protein cleaving enzyme inhibitors. A unique class of small molecules, gamma-secretase modulators (GSMs), selectively reduce Abeta1-42 production, and may also decrease Abeta1-40 while simultaneously increasing one or more shorter Abeta peptides, such as Abeta1-38 and Abeta1-37. GSMs are particularly attractive because they do not alter the total amount of Abeta peptides produced by gamma-secretase activity; they spare the processing of other gamma-secretase substrates, such as Notch; and they do not cause accumulation of the potentially toxic processing intermediate, beta-C-terminal fragment. This report describes the translation of pharmacological activity across species for two novel GSMs, (S)-7-(4 fluorophenyl)-N2-(3-methoxy-4-(3-methyl-1H-1,2,4-triazol-1-yl)phenyl)-N4-methyl 6,7-dihydro-5H-cyclopenta[d]pyrimidine-2,4-diamine (BMS-932481) and (S,Z)-17-(4 chloro-2-fluorophenyl)-34-(3-methyl-1H-1,2,4-triazol-1-yl)-16,17-dihydro-15H-4 oxa-2,9-diaza-1(2,4)-cyclopenta[d]pyrimidina-3(1,3)-benzenacyclononaphan-6-ene (BMS-986133). These GSMs are highly potent in vitro, exhibit dose- and time dependent activity in vivo, and have consistent levels of pharmacological effect across rats, dogs, monkeys, and human subjects. In rats, the two GSMs exhibit similar pharmacokinetics/pharmacodynamics between the brain and cerebrospinal fluid. In all species, GSM treatment decreased Abeta1-42 and Abeta1-40 levels while increasing Abeta1-38 and Abeta1-37 by a corresponding amount. Thus, the GSM mechanism and central activity translate across preclinical species and humans, thereby validating this therapeutic modality for potential utility in AD. PMID- 27189977 TI - The X-linked inhibitor of apoptosis regulates long-term depression and learning rate. AB - Hippocampal long-term depression (LTD) is an active form of synaptic plasticity that is necessary for consolidation of spatial memory, contextual fear memory, and novelty acquisition. Recent studies have shown that caspases (CASPs) play an important role in NMDA receptor-dependent LTD and are involved in postsynaptic remodeling and synaptic maturation. In the present study, we examined the role of X-linked inhibitor of apoptosis (XIAP), a putative endogenous CASP inhibitor, in synaptic plasticity in the hippocampus. Analysis in acute brain slices and in cultured hippocampal neurons revealed that XIAP deletion increases CASP-3 activity, enhances alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor internalization, sharply increases LTD, and significantly reduces synapse density. In vivo behaviors related to memory were also altered in XIAP(-/ ) mice, with faster acquisition of spatial object location and increased fear memory observed. Together, these results indicate that XIAP plays an important physiologic role in regulating sublethal CASP-3 activity within central neurons and thereby facilitates synaptic plasticity and memory acquisition.-Gibon, J., Unsain, N., Gamache, K., Thomas, R. A., De Leon, A., Johnstone, A., Nader, K., Seguela, P., Barker, P. A. The X-linked inhibitor of apoptosis regulates long term depression and learning rate. PMID- 27189978 TI - Transport of vitamin A across blood-tissue barriers is facilitated by STRA6. AB - Vitamin A bound to retinol binding protein 4 (RBP4) constitutes the major transport mode for retinoids in fasting circulation. Emerging evidence suggests that membrane protein, STRA6 (stimulated by retinoic acid 6), is the RBP4 receptor and vitamin A channel; however, the role of STRA6 in vitamin A homeostasis remains to be defined in vivo We subjected Stra6-knockout mice to diets sufficient and insufficient for vitamin A and used heterozygous siblings as controls. We determined vitamin A levels of the eyes, brain, and testis, which highly express Stra6, as well as of tissues with low expression, such as lung and fat. We also studied the consequence of STRA6 deficiency on retinoid-dependent processes in tissues. Furthermore, we examined how STRA6 deficiency affected retinoid homeostasis of the aging mouse. The picture that emerged indicates a critical role for STRA6 in the transport of vitamin A across blood-tissue barriers in the eyes, brain, and testis. Concurrently, fat and lung rely on dietary vitamin A. In testis and brain, Stra6 expression was regulated by vitamin A. In controls, this regulation reduced vitamin A consumption when the dietary supply was limited, sequestering it for the eye. Thus, STRA6 is critical for vitamin A homeostasis and the adaption of this process to the fluctuating supply of the vitamin.-Kelly, M., Widjaja-Adhi, M. A. K., Palczewski, G., von Lintig, J. Transport of vitamin A across blood-tissue barriers is facilitated by STRA6. PMID- 27189979 TI - Methanogenesis and the Wood-Ljungdahl Pathway: An Ancient, Versatile, and Fragile Association. AB - Methanogenesis coupled to the Wood-Ljungdahl pathway is one of the most ancient metabolisms for energy generation and carbon fixation in the Archaea. Recent results are sensibly changing our view on the diversity of methane-cycling capabilities in this Domain of Life. The availability of genomic sequences from uncharted branches of the archaeal tree has highlighted the existence of novel methanogenic lineages phylogenetically distant to previously known ones, such as the Methanomassiliicoccales. At the same time, phylogenomic analyses have suggested a methanogenic ancestor for all Archaea, implying multiple independent losses of this metabolism during archaeal diversification. This prediction has been strengthened by the report of genes involved in methane cycling in members of the Bathyarchaeota (a lineage belonging to the TACK clade), representing the first indication of the presence of methanogenesis outside of the Euryarchaeota. In light of these new data, we discuss how the association between methanogenesis and the Wood-Ljungdahl pathway appears to be much more flexible than previously thought, and might provide information on the processes that led to loss of this metabolism in many archaeal lineages. The combination of environmental microbiology, experimental characterization and phylogenomics opens up exciting avenues of research to unravel the diversity and evolutionary history of fundamental metabolic pathways. PMID- 27189982 TI - The Unicellular Ancestry of Groucho-Mediated Repression and the Origins of Metazoan Transcription Factors. AB - Groucho is a co-repressor that interacts with many transcription factors playing a crucial role in animal development. The evolutionary origins of Groucho are not clear. It is generally regarded as being a distinct animal-specific protein, although with similarities to the yeast Tup-like proteins. Here, it is shown that Groucho has true orthologs in unicellular relatives of animals. Based on their phylogenetic distribution, and an analysis of ligand-binding residues, these genes are unlikely to be orthologs of the fungal Tup-like genes. By identifying conserved candidate Groucho interaction motifs (GIMs) in nonmetazoan transcription factors, it is demonstrated that the details of molecular interactions between Groucho and transcription factors are likely to have been established prior to the origin of animals, but that the association of GIMs with many transcription factor types can be regarded as a metazoan innovation. PMID- 27189981 TI - Comparative Expression Dynamics of Intergenic Long Noncoding RNAs in the Genus Drosophila. AB - Thousands of long noncoding RNAs (lncRNAs) have been annotated in eukaryotic genomes, but comparative transcriptomic approaches are necessary to understand their biological impact and evolution. To facilitate such comparative studies in Drosophila, we identified and characterized lncRNAs in a second Drosophilid-the evolutionary model Drosophila pseudoobscura Using RNA-Seq and computational filtering of protein-coding potential, we identified 1,589 intergenic lncRNA loci in D. pseudoobscura We surveyed multiple sex-specific developmental stages and found, like in Drosophila melanogaster, increasingly prolific lncRNA expression through male development and an overrepresentation of lncRNAs in the testes. Other trends seen in D. melanogaster, like reduced pupal expression, were not observed. Nonrandom distributions of female-biased and non-testis-specific male biased lncRNAs between the X chromosome and autosomes are consistent with selection-based models of gene trafficking to optimize genomic location of sex biased genes. The numerous testis-specific lncRNAs, however, are randomly distributed between the X and autosomes, and we cannot reject the hypothesis that many of these are likely to be spurious transcripts. Finally, using annotated lncRNAs in both species, we identified 134 putative lncRNA homologs between D. pseudoobscura and D. melanogaster and find that many have conserved developmental expression dynamics, making them ideal candidates for future functional analyses. PMID- 27189980 TI - The Role of microRNAs in the Repeated Parallel Diversification of Lineages of Midas Cichlid Fish from Nicaragua. AB - Cichlid fishes are an ideal model system for studying biological diversification because they provide textbook examples of rapid speciation. To date, there has been little focus on the role of gene regulation during cichlid speciation. However, in recent years, gene regulation has been recognized as a powerful force linking diversification in gene function to speciation. Here, we investigated the potential role of miRNA regulation in the diversification of six cichlid species of the Midas cichlid lineage (Amphilophus spp.) inhabiting the Nicaraguan crater lakes. Using several genomic resources, we inferred 236 Midas miRNA genes that were used to predict the miRNA target sites on 8,232 Midas 3'-UTRs. Using population genomic calculations of SNP diversity, we found the miRNA genes to be more conserved than protein coding genes. In contrast to what has been observed in other cichlid fish, but similar to what has been typically found in other groups, we observed genomic signatures of purifying selection on the miRNA targets by comparing these sites with the less conserved nontarget portion of the 3'-UTRs. However, in one species pair that has putatively speciated sympatrically in crater Lake Apoyo, we recovered a different pattern of relaxed purifying selection and high genetic divergence at miRNA targets. Our results suggest that sequence evolution at miRNA binding sites could be a critical genomic mechanism contributing to the rapid phenotypic evolution of Midas cichlids. PMID- 27189983 TI - Pangenome Evolution in the Marine Bacterium Alteromonas. AB - We have examined a collection of the free-living marine bacterium Alteromonas genomes with cores diverging in average nucleotide identities ranging from 99.98% to 73.35%, i.e., from microbes that can be considered members of a natural clone (like in a clinical epidemiological outbreak) to borderline genus level. The genomes were largely syntenic allowing a precise delimitation of the core and flexible regions in each. The core was 1.4 Mb (ca. 30% of the typical strain genome size). Recombination rates along the core were high among strains belonging to the same species (37.7-83.7% of all nucleotide polymorphisms) but they decreased sharply between species (18.9-5.1%). Regarding the flexible genome, its main expansion occurred within the boundaries of the species, i.e., strains of the same species already have a large and diverse flexible genome. Flexible regions occupy mostly fixed genomic locations. Four large genomic islands are involved in the synthesis of strain-specific glycosydic receptors that we have called glycotypes. These genomic regions are exchanged by homologous recombination within and between species and there is evidence for their import from distant taxonomic units (other genera within the family). In addition, several hotspots for integration of gene cassettes by illegitimate recombination are distributed throughout the genome. They code for features that give each clone specific properties to interact with their ecological niche and must flow fast throughout the whole genus as they are found, with nearly identical sequences, in different species. Models for the generation of this genomic diversity involving phage predation are discussed. PMID- 27189984 TI - Diversity of Group I and II Clostridium botulinum Strains from France Including Recently Identified Subtypes. AB - In France, human botulism is mainly food-borne intoxication, whereas infant botulism is rare. A total of 99 group I and II Clostridium botulinum strains including 59 type A (12 historical isolates [1947-1961], 43 from France [1986 2013], 3 from other countries, and 1 collection strain), 31 type B (3 historical, 23 recent isolates, 4 from other countries, and 1 collection strain), and 9 type E (5 historical, 3 isolates, and 1 collection strain) were investigated by botulinum locus gene sequencing and multilocus sequence typing analysis. Historical C. botulinum A strains mainly belonged to subtype A1 and sequence type (ST) 1, whereas recent strains exhibited a wide genetic diversity: subtype A1 in orfX or ha locus, A1(B), A1(F), A2, A2b2, A5(B2') A5(B3'), as well as the recently identified A7 and A8 subtypes, and were distributed into 25 STs. Clostridium botulinum A1(B) was the most frequent subtype from food-borne botulism and food. Group I C. botulinum type B in France were mainly subtype B2 (14 out of 20 historical and recent strains) and were divided into 19 STs. Food borne botulism resulting from ham consumption during the recent period was due to group II C. botulinum B4. Type E botulism is rare in France, 5 historical and 1 recent strains were subtype E3. A subtype E12 was recently identified from an unusual ham contamination. Clostridium botulinum strains from human botulism in France showed a wide genetic diversity and seems to result not from a single evolutionary lineage but from multiple and independent genetic rearrangements. PMID- 27189986 TI - DnaK-Dependent Accelerated Evolutionary Rate in Prokaryotes. AB - Many proteins depend on an interaction with molecular chaperones in order to fold into a functional tertiary structure. Previous studies showed that protein interaction with the GroEL/GroES chaperonine and Hsp90 chaperone can buffer the impact of slightly deleterious mutations in the protein sequence. This capacity of GroEL/GroES to prevent protein misfolding has been shown to accelerate the evolution of its client proteins. Whether other bacterial chaperones have a similar effect on their client proteins is currently unknown. Here, we study the impact of DnaK (Hsp70) chaperone on the evolution of its client proteins. Evolutionary parameters were derived from comparison of the Escherichia coli proteome to 1,808,565 orthologous proteins in 1,149 proteobacterial genomes. Our analysis reveals a significant positive correlation between protein binding frequency with DnaK and evolutionary rate. Proteins with high binding affinity to DnaK evolve on average 4.3-fold faster than proteins in the lowest binding affinity class at the genus resolution. Differences in evolutionary rates of DnaK interactor classes are still significant after adjusting for possible effects caused by protein expression level. Furthermore, we observe an additive effect of DnaK and GroEL chaperones on the evolutionary rates of their common interactors. Finally, we found pronounced similarities in the physicochemical profiles that characterize proteins belonging to DnaK and GroEL interactomes. Our results thus implicate DnaK-mediated folding as a major component in shaping protein evolutionary dynamics in bacteria and supply further evidence for the long-term manifestation of chaperone-mediated folding on genome evolution. PMID- 27189985 TI - Opsin Repertoire and Expression Patterns in Horseshoe Crabs: Evidence from the Genome of Limulus polyphemus (Arthropoda: Chelicerata). AB - Horseshoe crabs are xiphosuran chelicerates, the sister group to arachnids. As such, they are important for understanding the most recent common ancestor of Euchelicerata and the evolution and diversification of Arthropoda. Limulus polyphemus is the most investigated of the four extant species of horseshoe crabs, and the structure and function of its visual system have long been a major focus of studies critical for understanding the evolution of visual systems in arthropods. Likewise, studies of genes encoding Limulus opsins, the protein component of the visual pigments, are critical for understanding opsin evolution and diversification among chelicerates, where knowledge of opsins is limited, and more broadly among arthropods. In the present study, we sequenced and assembled a high quality nuclear genomic sequence of L. polyphemus and used these data to annotate the full repertoire of Limulus opsins. We conducted a detailed phylogenetic analysis of Limulus opsins, including using gene structure and synteny information to identify relationships among different opsin classes. We used our phylogeny to identify significant genomic events that shaped opsin evolution and therefore the visual system of Limulus We also describe the tissue expression patterns of the 18 opsins identified and show that transcripts encoding a number, including a peropsin, are present throughout the central nervous system. In addition to significantly extending our understanding of photosensitivity in Limulus and providing critical insight into the genomic evolution of horseshoe crab opsins, this work provides a valuable genomic resource for addressing myriad questions related to xiphosuran physiology and arthropod evolution. PMID- 27189987 TI - The Small Nuclear Genomes of Selaginella Are Associated with a Low Rate of Genome Size Evolution. AB - The haploid nuclear genome size (1C DNA) of vascular land plants varies over several orders of magnitude. Much of this observed diversity in genome size is due to the proliferation and deletion of transposable elements. To date, all vascular land plant lineages with extremely small nuclear genomes represent recently derived states, having ancestors with much larger genome sizes. The Selaginellaceae represent an ancient lineage with extremely small genomes. It is unclear how small nuclear genomes evolved in Selaginella We compared the rates of nuclear genome size evolution in Selaginella and major vascular plant clades in a comparative phylogenetic framework. For the analyses, we collected 29 new flow cytometry estimates of haploid genome size in Selaginella to augment publicly available data. Selaginella possess some of the smallest known haploid nuclear genome sizes, as well as the lowest rate of genome size evolution observed across all vascular land plants included in our analyses. Additionally, our analyses provide strong support for a history of haploid nuclear genome size stasis in Selaginella Our results indicate that Selaginella, similar to other early diverging lineages of vascular land plants, has relatively low rates of genome size evolution. Further, our analyses highlight that a rapid transition to a small genome size is only one route to an extremely small genome. PMID- 27189988 TI - Nuclear Architecture and Patterns of Molecular Evolution Are Correlated in the Ciliate Chilodonella uncinata. AB - The relationship between nuclear architecture and patterns of molecular evolution in lineages across the eukaryotic tree of life is not well understood, partly because molecular evolution is traditionally explored as changes in base pairs along a linear sequence without considering the context of nuclear position of chromosomes. The ciliate Chilodonella uncinata is an ideal system to address the relationship between nuclear architecture and patterns of molecular evolution as the somatic macronucleus of this ciliate is composed of a peripheral DNA-rich area (orthomere) and a DNA-poor central region (paramere) to form a "heteromeric" macronucleus. Moreover, because the somatic chromosomes of C. uncinata are highly processed into "gene-sized" chromosomes (i.e., nanochromosomes), we can assess fine-scale relationships between location and sequence evolution. By combining fluorescence microscopy and analyses of transcriptome data from C. uncinata, we find that highly expressed genes have the greatest codon usage bias and are enriched in DNA-poor regions. In contrast, genes with less biased sequences tend to be concentrated in DNA abundant areas, at least during vegetative growth. Our analyses are consistent with recent work in plants and animals where nuclear architecture plays a role in gene expression. At the same time, the unusual localization of nanochromosomes suggests that the highly structured nucleus in C. uncinata may create a "gene bank" that facilitates rapid changes in expression of genes required only in specific life history stages. By using "nonmodel" organisms like C. uncinata, we can explore the universality of eukaryotic features while also providing examples of novel properties (i.e., the presence of a gene bank) that build from these features. PMID- 27189989 TI - Ancient Eukaryotic Origin and Evolutionary Plasticity of Nuclear Lamina. AB - The emergence of the nucleus was a major event of eukaryogenesis. How the nuclear envelope (NE) arose and acquired functions governing chromatin organization and epigenetic control has direct bearing on origins of developmental/stage-specific expression programs. The configuration of the NE and the associated lamina in the last eukaryotic common ancestor (LECA) is of major significance and can provide insight into activities within the LECA nucleus. Subsequent lamina evolution, alterations, and adaptations inform on the variation and selection of distinct mechanisms that subtend gene expression in distinct taxa. Understanding lamina evolution has been difficult due to the diversity and limited taxonomic distributions of the three currently known highly distinct nuclear lamina. We rigorously searched available sequence data for an expanded view of the distribution of known lamina and lamina-associated proteins. While the lamina proteins of plants and trypanosomes are indeed taxonomically restricted, homologs of metazoan lamins and key lamin-binding proteins have significantly broader distributions, and a lamin gene tree supports vertical evolution from the LECA. Two protist lamins from highly divergent taxa target the nucleus in mammalian cells and polymerize into filamentous structures, suggesting functional conservation of distant lamin homologs. Significantly, a high level of divergence of lamin homologs within certain eukaryotic groups and the apparent absence of lamins and/or the presence of seemingly different lamina proteins in many eukaryotes suggests great evolutionary plasticity in structures at the NE, and hence mechanisms of chromatin tethering and epigenetic gene control. PMID- 27189990 TI - Genus-Wide Comparative Genome Analyses of Colletotrichum Species Reveal Specific Gene Family Losses and Gains during Adaptation to Specific Infection Lifestyles. AB - Members from Colletotrichum genus adopt a diverse range of lifestyles during infection of plants and represent a group of agriculturally devastating pathogens. In this study, we present the draft genome of Colletotrichum incanum from the spaethianum clade of Colletotrichum and the comparative analyses with five other Colletotrichum species from distinct lineages. We show that the C. incanum strain, originally isolated from Japanese daikon radish, is able to infect both eudicot plants, such as certain ecotypes of the eudicot Arabidopsis, and monocot plants, such as lily. Being closely related to Colletotrichum species both in the graminicola clade, whose members are restricted strictly to monocot hosts, and to the destructivum clade, whose members are mostly associated with dicot infections, C. incanum provides an interesting model system for comparative genomics to study how fungal pathogens adapt to monocot and dicot hosts. Genus wide comparative genome analyses reveal that Colletotrichum species have tailored profiles of their carbohydrate-degrading enzymes according to their infection lifestyles. In addition, we show evidence that positive selection acting on secreted and nuclear localized proteins that are highly conserved may be important in adaptation to specific hosts or ecological niches. PMID- 27189991 TI - Pooled Enrichment Sequencing Identifies Diversity and Evolutionary Pressures at NLR Resistance Genes within a Wild Tomato Population. AB - Nod-like receptors (NLRs) are nucleotide-binding domain and leucine-rich repeats containing proteins that are important in plant resistance signaling. Many of the known pathogen resistance (R) genes in plants are NLRs and they can recognize pathogen molecules directly or indirectly. As such, divergence and copy number variants at these genes are found to be high between species. Within populations, positive and balancing selection are to be expected if plants coevolve with their pathogens. In order to understand the complexity of R-gene coevolution in wild nonmodel species, it is necessary to identify the full range of NLRs and infer their evolutionary history. Here we investigate and reveal polymorphism occurring at 220 NLR genes within one population of the partially selfing wild tomato species Solanum pennellii. We use a combination of enrichment sequencing and pooling ten individuals, to specifically sequence NLR genes in a resource and cost-effective manner. We focus on the effects which different mapping and single nucleotide polymorphism calling software and settings have on calling polymorphisms in customized pooled samples. Our results are accurately verified using Sanger sequencing of polymorphic gene fragments. Our results indicate that some NLRs, namely 13 out of 220, have maintained polymorphism within our S. pennellii population. These genes show a wide range of piN/piS ratios and differing site frequency spectra. We compare our observed rate of heterozygosity with expectations for this selfing and bottlenecked population. We conclude that our method enables us to pinpoint NLR genes which have experienced natural selection in their habitat. PMID- 27189993 TI - Genomic Signatures of Speciation in Sympatric and Allopatric Hawaiian Picture Winged Drosophila. AB - The Hawaiian archipelago provides a natural arena for understanding adaptive radiation and speciation. The Hawaiian Drosophila are one of the most diverse endemic groups in Hawaii with up to 1,000 species. We sequenced and analyzed entire genomes of recently diverged species of Hawaiian picture-winged Drosophila, Drosophila silvestris and Drosophila heteroneura from Hawaii Island, in comparison with Drosophila planitibia, their sister species from Maui, a neighboring island where a common ancestor of all three had likely occurred. Genome-wide single nucleotide polymorphism patterns suggest the more recent origin of D. silvestris and D. heteroneura, as well as a pervasive influence of positive selection on divergence of the three species, with the signatures of positive selection more prominent in sympatry than allopatry. Positively selected genes were significantly enriched for functional terms related to sensory detection and mating, suggesting that sexual selection played an important role in speciation of these species. In particular, sequence variation in Olfactory receptor and Gustatory receptor genes seems to play a major role in adaptive radiation in Hawaiian pictured-winged Drosophila. PMID- 27189992 TI - Detection of Allelic Frequency Differences between the Sexes in Humans: A Signature of Sexually Antagonistic Selection. AB - Sexually antagonistic (SA) selection, a form of selection that can occur when both sexes have different fitness optima for a trait, is a major force shaping the evolution of organisms. A seminal model developed by Rice (Rice WR. 1984. Sex chromosomes and the evolution of sexual dimorphism. Evolution 38:735-742.) predicts that the X chromosome should be a hotspot for the accumulation of loci under SA selection as compared with the autosomes. Here, we propose a methodological framework designed to detect a specific signature of SA selection on viability, differences in allelic frequencies between the sexes. Applying this method on genome-wide single nucleotide polymorphism (SNP) data in human populations where no sex-specific population stratification could be detected, we show that there are overall significantly more SNPs exhibiting differences in allelic frequencies between the sexes on the X chromosome as compared with autosomes, supporting the predictions of Rice's model. This pattern is consistent across populations and is robust to correction for potential biases such as differences in linkage disequilibrium, sample size, and genotyping errors between chromosomes. Although SA selection is not the only factor resulting in allelic frequency differences between the sexes, we further show that at least part of the identified X-linked loci is caused by such a sex-specific processes. PMID- 27189994 TI - C-Terminal Region of Sulfite Reductase Is Important to Localize to Chloroplast Nucleoids in Land Plants. AB - Chloroplast (cp) DNA is compacted into cpDNA-protein complexes, called cp nucleoids. An abundant and extensively studied component of cp nucleoids is the bifunctional protein sulfite reductase (SiR). The preconceived role of SiR as the core cp nucleoid protein, however, is becoming less likely because of the recent findings that SiRs do not associate with cp nucleoids in some plant species, such as Zea mays and Arabidopsis thaliana To address this discrepancy, we have performed a detailed phylogenetic analysis of SiRs, which shows that cp nucleoid type SiRs share conserved C-terminally encoded peptides (CEPs). The CEPs are likely to form a bacterial ribbon-helix-helix DNA-binding motif, implying a potential role in attaching SiRs onto cp nucleoids. A proof-of-concept experiment was conducted by fusing the nonnucleoid-type SiR from A. thaliana (AtSiR) with the CEP from the cp nucleoid-type SiR of Phaseolus vulgaris The addition of the CEP drastically altered the intra-cp localization of AtSiR to cp nucleoids. Our analysis supports the possible functions of CEPs in determining the localization of SiRs to cp nucleoids and illuminates a possible evolutionary scenario for SiR as a cp nucleoid protein. PMID- 27189995 TI - Evolutionary Transitions of MicroRNA-Target Pairs. AB - How newly generated microRNA (miRNA) genes are integrated into gene regulatory networks during evolution is fundamental in understanding the molecular and evolutionary bases of robustness and plasticity in gene regulation. A recent model proposed that after the birth of a miRNA, the miRNA is generally integrated into the network by decreasing the number of target genes during evolution. However, this decreasing model remains to be carefully examined by considering in vivo conditions. In this study, we therefore compared the number of target genes among miRNAs with different ages, combining experiments with bioinformatics predictions. First, we focused on three Drosophila miRNAs with different ages. As a result, we found that an older miRNA has a greater number of target genes than a younger miRNA, suggesting the increasing number of targets for each miRNA during evolution (increasing model). To further confirm our results, we also predicted all target genes for all miRNAs in D. melanogaster, considering co expression of miRNAs and mRNAs in vivo The results obtained also do not support the decreasing model but are reasonably consistent with the increasing model of miRNA-target pairs. Furthermore, our large-scale analyses of currently available experimental data of miRNA-target pairs also showed a weak but the same trend in humans. These results indicate that the current decreasing model of miRNA-target pairs should be reconsidered and the increasing model may be more appropriate to explain the evolutionary transitions of miRNA-target pairs in many organisms. PMID- 27189997 TI - Antibiotic Resistance, Core-Genome and Protein Expression in IncHI1 Plasmids in Salmonella Typhimurium. AB - Conjugative plasmids from the IncHI1 incompatibility group play an important role in transferring antibiotic resistance in Salmonella Typhimurium. However, knowledge of their genome structure or gene expression is limited. In this study, we determined the complete nucleotide sequences of four IncHI1 plasmids transferring resistance to antibiotics by two different next generation sequencing protocols and protein expression by mass spectrometry. Sequence data including additional 11 IncHI1 plasmids from GenBank were used for the definition of the IncHI1 plasmid core-genome and pan-genome. The core-genome consisted of approximately 123 kbp and 122 genes while the total pan-genome represented approximately 600 kbp. When the core-genome sequences were used for multiple alignments, the 15 tested IncHI1 plasmids were separated into two main lineages. GC content in core-genome genes was around 46% and 50% in accessory genome genes. A multidrug resistance region present in all 4 sequenced plasmids extended over 20 kbp and, except for tet(B), the genes responsible for antibiotic resistance were those with the highest GC content. IncHI1 plasmids therefore represent replicons that evolved in low GC content bacteria. From their original host, they spread to Salmonella and during this spread these plasmids acquired multiple accessory genes including those coding for antibiotic resistance. Antibiotic resistance genes belonged to genes with the highest level of expression and were constitutively expressed even in the absence of antibiotics. This is the likely mechanism that facilitates host cell survival when antibiotics suddenly emerge in the environment. PMID- 27189998 TI - The Frequency of Internal Shine-Dalgarno-like Motifs in Prokaryotes. AB - In prokaryotes, translation initiation typically depends on complementary binding between a G-rich Shine-Dalgarno (SD) motif in the 5' untranslated region of mRNAs, and the 3' tail of the 16S ribosomal RNA (the anti-SD sequence). In some cases, internal SD-like motifs in the coding region generate "programmed" ribosomal pauses that are beneficial for protein folding or accurate targeting. On the other hand, such pauses can also reduce protein production, generating purifying selection against internal SD-like motifs. This selection should be stronger in GC-rich genomes that are more likely to harbor the G-rich SD motif. However, the nature and consequences of selection acting on internal SD-like motifs within genomes and across species remains unclear. We analyzed the frequency of SD-like hexamers in the coding regions of 284 prokaryotes (277 with known anti-SD sequences and 7 without a typical SD mechanism). After accounting for GC content, we found that internal SD-like hexamers are avoided in 230 species, including three without a typical SD mechanism. The degree of avoidance was higher in GC-rich genomes, mesophiles, and N-terminal regions of genes. In contrast, 54 species either showed no signature of avoidance or were enriched in internal SD-like motifs. C-terminal gene regions were relatively enriched in SD like hexamers, particularly for genes in operons or those followed closely by downstream genes. Together, our results suggest that the frequency of internal SD like hexamers is governed by multiple factors including GC content and genome organization, and further empirical work is necessary to understand the evolution and functional roles of these motifs. PMID- 27189996 TI - Comparative Genomics of Two Closely Related Wolbachia with Different Reproductive Effects on Hosts. AB - Wolbachia pipientis are obligate intracellular bacteria commonly found in many arthropods. They can induce various reproductive alterations in hosts, including cytoplasmic incompatibility, male-killing, feminization, and parthenogenetic development, and can provide host protection against some viruses and other pathogens. Wolbachia differ from many other primary endosymbionts in arthropods because they undergo frequent horizontal transmission between hosts and are well known for an abundance of mobile elements and relatively high recombination rates. Here, we compare the genomes of two closely related Wolbachia (with 0.57% genome-wide synonymous divergence) that differ in their reproductive effects on hosts. wVitA induces a sperm-egg incompatibility (also known as cytoplasmic incompatibility) in the parasitoid insect Nasonia vitripennis, whereas wUni causes parthenogenetic development in a different parasitoid, Muscidifurax uniraptor Although these bacteria are closely related, the genomic comparison reveals rampant rearrangements, protein truncations (particularly in proteins predicted to be secreted), and elevated substitution rates. These changes occur predominantly in the wUni lineage, and may be due in part to adaptations by wUni to a new host environment, or its phenotypic shift to parthenogenesis induction. However, we conclude that the approximately 8-fold elevated synonymous substitution rate in wUni is due to a either an elevated mutation rate or a greater number of generations per year in wUni, which occurs in semitropical host species. We identify a set of genes whose loss or pseudogenization in the wUni lineage implicates them in the phenotypic shift from cytoplasmic incompatibility to parthenogenesis induction. Finally, comparison of these closely related strains allows us to determine the fine-scale mutation patterns in Wolbachia Although Wolbachia are AT rich, mutation probabilities estimated from 4-fold degenerate sites are not AT biased, and predict an equilibrium AT content much less biased than observed (57-50% AT predicted vs. 76% current content at degenerate sites genome wide). The contrast suggests selection for increased AT content within Wolbachia genomes. PMID- 27189999 TI - Capturing the Phylogeny of Holometabola with Mitochondrial Genome Data and Bayesian Site-Heterogeneous Mixture Models. AB - After decades of debate, a mostly satisfactory resolution of relationships among the 11 recognized holometabolan orders of insects has been reached based on nuclear genes, resolving one of the most substantial branches of the tree-of life, but the relationships are still not well established with mitochondrial genome data. The main reasons have been the absence of sufficient data in several orders and lack of appropriate phylogenetic methods that avoid the systematic errors from compositional and mutational biases in insect mitochondrial genomes. In this study, we assembled the richest taxon sampling of Holometabola to date (199 species in 11 orders), and analyzed both nucleotide and amino acid data sets using several methods. We find the standard Bayesian inference and maximum likelihood analyses were strongly affected by systematic biases, but the site heterogeneous mixture model implemented in PhyloBayes avoided the false grouping of unrelated taxa exhibiting similar base composition and accelerated evolutionary rate. The inclusion of rRNA genes and removal of fast-evolving sites with the observed variability sorting method for identifying sites deviating from the mean rates improved the phylogenetic inferences under a site-heterogeneous model, correctly recovering most deep branches of the Holometabola phylogeny. We suggest that the use of mitochondrial genome data for resolving deep phylogenetic relationships requires an assessment of the potential impact of substitutional saturation and compositional biases through data deletion strategies and by using site-heterogeneous mixture models. Our study suggests a practical approach for how to use densely sampled mitochondrial genome data in phylogenetic analyses. PMID- 27190000 TI - Teff, an Orphan Cereal in the Chloridoideae, Provides Insights into the Evolution of Storage Proteins in Grasses. AB - Seed storage proteins (SSP) in cereals provide essential nutrition for humans and animals. Genes encoding these proteins have undergone rapid evolution in different grass species. To better understand the degree of divergence, we analyzed this gene family in the subfamily Chloridoideae, where the genome of teff (Eragrostis tef) has been sequenced. We find gene duplications, deletions, and rapid mutations in protein-coding sequences. The main SSPs in teff, like other grasses, are prolamins, here called eragrostins. Teff has gamma- and delta prolamins, but has no beta-prolamins. One delta-type prolamin (delta1) in teff has higher methionine (33%) levels than in maize (23-25%). The other delta-type prolamin (delta2) has reduced methionine residues (<10%) and is phylogenetically closer to alpha prolamins. Prolamin delta2 in teff represents an intermediate between delta and alpha types that appears to have been lost in maize and other Panicoideae, and was replaced by the expansion of alpha-prolamins. Teff also has considerably larger numbers of alpha-prolamin genes, which we further divide into five sub-groups, where alpha2 and alpha5 represent the most abundant alpha prolamins both in number and in expression. In addition, indolines that determine kernel softness are present in teff and the panicoid cereal called foxtail millet (Setaria italica) but not in sorghum or maize, indicating that these genes were only recently lost in some members of the Panicoideae Moreover, this study provides not only information on the evolution of SSPs in the grass family but also the importance of alpha-globulins in protein aggregation and germplasm divergence. PMID- 27190002 TI - Breaking Good: Accounting for Fragility of Genomic Regions in Rearrangement Distance Estimation. AB - Models of evolution by genome rearrangements are prone to two types of flaws: One is to ignore the diversity of susceptibility to breakage across genomic regions, and the other is to suppose that susceptibility values are given. Without necessarily supposing their precise localization, we call "solid" the regions that are improbably broken by rearrangements and "fragile" the regions outside solid ones. We propose a model of evolution by inversions where breakage probabilities vary across fragile regions and over time. It contains as a particular case the uniform breakage model on the nucleotidic sequence, where breakage probabilities are proportional to fragile region lengths. This is very different from the frequently used pseudouniform model where all fragile regions have the same probability to break. Estimations of rearrangement distances based on the pseudouniform model completely fail on simulations with the truly uniform model. On pairs of amniote genomes, we show that identifying coding genes with solid regions yields incoherent distance estimations, especially with the pseudouniform model, and to a lesser extent with the truly uniform model. This incoherence is solved when we coestimate the number of fragile regions with the rearrangement distance. The estimated number of fragile regions is surprisingly small, suggesting that a minority of regions are recurrently used by rearrangements. Estimations for several pairs of genomes at different divergence times are in agreement with a slowly evolvable colocalization of active genomic regions in the cell. PMID- 27190001 TI - Plastid-Nuclear Interaction and Accelerated Coevolution in Plastid Ribosomal Genes in Geraniaceae. AB - Plastids and mitochondria have many protein complexes that include subunits encoded by organelle and nuclear genomes. In animal cells, compensatory evolution between mitochondrial and nuclear-encoded subunits was identified and the high mitochondrial mutation rates were hypothesized to drive compensatory evolution in nuclear genomes. In plant cells, compensatory evolution between plastid and nucleus has rarely been investigated in a phylogenetic framework. To investigate plastid-nuclear coevolution, we focused on plastid ribosomal protein genes that are encoded by plastid and nuclear genomes from 27 Geraniales species. Substitution rates were compared for five sets of genes representing plastid- and nuclear-encoded ribosomal subunit proteins targeted to the cytosol or the plastid as well as nonribosomal protein controls. We found that nonsynonymous substitution rates (dN) and the ratios of nonsynonymous to synonymous substitution rates (omega) were accelerated in both plastid- (CpRP) and nuclear encoded subunits (NuCpRP) of the plastid ribosome relative to control sequences. Our analyses revealed strong signals of cytonuclear coevolution between plastid- and nuclear-encoded subunits, in which nonsynonymous substitutions in CpRP and NuCpRP tend to occur along the same branches in the Geraniaceae phylogeny. This coevolution pattern cannot be explained by physical interaction between amino acid residues. The forces driving accelerated coevolution varied with cellular compartment of the sequence. Increased omega in CpRP was mainly due to intensified positive selection whereas increased omega in NuCpRP was caused by relaxed purifying selection. In addition, the many indels identified in plastid rRNA genes in Geraniaceae may have contributed to changes in plastid subunits. PMID- 27190005 TI - The Somatic Nature of Cancer Allows It to Affect Highly Constrained Genes. AB - Cancer is special among genetic disorders in two major ways: first, cancer is a disease of the most basic of cellular functions, such as cell proliferation, differentiation, and the maintenance of genomic integrity. Second, in contrast to most genetic disorders that are mediated by germline (hereditary) mutations, cancer is largely a somatic disease. Here we show that these two traits are not detached and that it is the somatic nature of cancer that allows it to affect the most basic of cellular functions. We begin by demonstrating that cancer genes are both more functionally central (as measured by their patterns of expression and protein interaction) and more evolutionarily constrained than non-cancer genetic disease genes. We then compare genes that are only modified somatically in cancer (hereinafter referred to as "somatic cancer genes") to those that can also be modified in a hereditary manner, contributing to cancer development (hereinafter referred to as "hereditary cancer genes"). We show that both somatic and hereditary cancer genes are much more functionally central than genes contributing to non-cancer genetic disorders. At the same time, hereditary cancer genes are only as constrained as non-cancer hereditary disease genes, while somatic cancer genes tend to be much more constrained in evolution. Thus, it appears that it is the somatic nature of cancer that allows it to modify the most constrained genes and, therefore, affect the most basic of cellular functions. PMID- 27190003 TI - The Role of Transcription Factors at Antisense-Expressing Gene Pairs in Yeast. AB - Genes encoded close to one another on the chromosome are often coexpressed, by a mechanism and regulatory logic that remain poorly understood. We surveyed the yeast genome for tandem gene pairs oriented tail-to-head at which expression antisense to the upstream gene was conserved across species. The intergenic region at most such tandem pairs is a bidirectional promoter, shared by the downstream gene mRNA and the upstream antisense transcript. Genomic analyses of these intergenic loci revealed distinctive patterns of transcription factor regulation. Mutation of a given transcription factor verified its role as a regulator in trans of tandem gene pair loci, including the proximally initiating upstream antisense transcript and downstream mRNA and the distally initiating upstream mRNA. To investigate cis-regulatory activity at such a locus, we focused on the stress-induced NAD(P)H dehydratase YKL151C and its downstream neighbor, the metabolic enzyme GPM1 Previous work has implicated the region between these genes in regulation of GPM1 expression; our mutation experiments established its function in rich medium as a repressor in cis of the distally initiating YKL151C sense RNA, and an activator of the proximally initiating YKL151C antisense RNA. Wild-type expression of all three transcripts required the transcription factor Gcr2. Thus, at this locus, the intergenic region serves as a focal point of regulatory input, driving antisense expression and mediating the coordinated regulation of YKL151C and GPM1 Together, our findings implicate transcription factors in the joint control of neighboring genes specialized to opposing conditions and the antisense transcripts expressed between them. PMID- 27190004 TI - Host-Associated Genomic Features of the Novel Uncultured Intracellular Pathogen Ca. Ichthyocystis Revealed by Direct Sequencing of Epitheliocysts. AB - Advances in single-cell and mini-metagenome sequencing have enabled important investigations into uncultured bacteria. In this study, we applied the mini metagenome sequencing method to assemble genome drafts of the uncultured causative agents of epitheliocystis, an emerging infectious disease in the Mediterranean aquaculture species gilthead seabream. We sequenced multiple cyst samples and constructed 11 genome drafts from a novel beta-proteobacterial lineage, Candidatus Ichthyocystis. The draft genomes demonstrate features typical of pathogenic bacteria with an obligate intracellular lifestyle: a reduced genome of up to 2.6 Mb, reduced G + C content, and reduced metabolic capacity. Reconstruction of metabolic pathways reveals that Ca Ichthyocystis genomes lack all amino acid synthesis pathways, compelling them to scavenge from the fish host. All genomes encode type II, III, and IV secretion systems, a large repertoire of predicted effectors, and a type IV pilus. These are all considered to be virulence factors, required for adherence, invasion, and host manipulation. However, no evidence of lipopolysaccharide synthesis could be found. Beyond the core functions shared within the genus, alignments showed distinction into different species, characterized by alternative large gene families. These comprise up to a third of each genome, appear to have arisen through duplication and diversification, encode many effector proteins, and are seemingly critical for virulence. Thus, Ca Ichthyocystis represents a novel obligatory intracellular pathogenic beta-proteobacterial lineage. The methods used: mini-metagenome analysis and manual annotation, have generated important insights into the lifestyle and evolution of the novel, uncultured pathogens, elucidating many putative virulence factors including an unprecedented array of novel gene families. PMID- 27190006 TI - Conserved Features in the Structure, Mechanism, and Biogenesis of the Inverse Autotransporter Protein Family. AB - The bacterial cell surface proteins intimin and invasin are virulence factors that share a common domain structure and bind selectively to host cell receptors in the course of bacterial pathogenesis. The beta-barrel domains of intimin and invasin show significant sequence and structural similarities. Conversely, a variety of proteins with sometimes limited sequence similarity have also been annotated as "intimin-like" and "invasin" in genome datasets, while other recent work on apparently unrelated virulence-associated proteins ultimately revealed similarities to intimin and invasin. Here we characterize the sequence and structural relationships across this complex protein family. Surprisingly, intimins and invasins represent a very small minority of the sequence diversity in what has been previously the "intimin/invasin protein family". Analysis of the assembly pathway for expression of the classic intimin, EaeA, and a characteristic example of the most prevalent members of the group, FdeC, revealed a dependence on the translocation and assembly module as a common feature for both these proteins. While the majority of the sequences in the grouping are most similar to FdeC, a further and widespread group is two-partner secretion systems that use the beta-barrel domain as the delivery device for secretion of a variety of virulence factors. This comprehensive analysis supports the adoption of the "inverse autotransporter protein family" as the most accurate nomenclature for the family and, in turn, has important consequences for our overall understanding of the Type V secretion systems of bacterial pathogens. PMID- 27190008 TI - Dynamic relationships between age, amyloid-beta deposition, and glucose metabolism link to the regional vulnerability to Alzheimer's disease. AB - SEE HANSSON AND GOURAS DOI101093/AWW146 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Although some brain regions such as precuneus and lateral temporo parietal cortex have been shown to be more vulnerable to Alzheimer's disease than other areas, a mechanism underlying the differential regional vulnerability to Alzheimer's disease remains to be elucidated. Using fluorodeoxyglucose and Pittsburgh compound B positron emission tomography imaging glucose metabolism and amyloid-beta deposition, we tested whether and how life-long changes in glucose metabolism relate to amyloid-beta deposition and Alzheimer's disease-related hypometabolism. Nine healthy young adults (age range: 20-30), 96 cognitively normal older adults (age range: 61-96), and 20 patients with Alzheimer's disease (age range: 50-90) were scanned using fluorodeoxyglucose and Pittsburgh compound B positron emission tomography. Among cognitively normal older subjects, 32 were further classified as amyloid-positive, with 64 as amyloid-negative. To assess the contribution of glucose metabolism to the regional vulnerability to amyloid beta deposition, we defined the highest and lowest metabolic regions in young adults and examined differences in amyloid deposition between these regions across groups. Two-way analyses of variance were conducted to assess regional differences in age and amyloid-beta-related changes in glucose metabolism. Multiple regressions were applied to examine the association between amyloid-beta deposition and regional glucose metabolism. Both region of interest and whole brain voxelwise analyses were conducted to complement and confirm the results derived from the other approach. Regional differences in glucose metabolism between the highest and lowest metabolism regions defined in young adults (T = 12.85, P < 0.001) were maintained both in Pittsburgh compound B-negative cognitively normal older subjects (T = 6.66, P < 0.001) and Pittsburgh compound B positive cognitively normal older subjects (T = 10.62, P < 0.001), but, only the Pittsburgh compound B-positive cognitively normal older subjects group showed significantly higher Pittsburgh compound B retention in the highest compared to the lowest glucose metabolism regions defined in young adults (T = 2.05, P < 0.05). Regional differences in age and amyloid-beta-dependent changes in glucose metabolism were found such that frontal glucose metabolism was reduced with age, while glucose metabolism in the precuneus was maintained across the lifespan (right hemisphere: F = 7.69, P < 0.001; left hemisphere: F = 8.69, P < 0.001). Greater Alzheimer's disease-related hypometabolism was observed in brain regions that showed both age-invariance and amyloid-beta-related increases in glucose metabolism. Our results indicate that although early and life-long regional variation in glucose metabolism relates to the regional vulnerability to amyloid beta accumulation, Alzheimer's disease-related hypometabolism is more specific to brain regions showing age-invariant glucose metabolism and amyloid-beta-related hypermetabolism. PMID- 27190007 TI - Reinventing the Wheel and Making It Round Again: Evolutionary Convergence in Buchnera-Serratia Symbiotic Consortia between the Distantly Related Lachninae Aphids Tuberolachnus salignus and Cinara cedri. AB - Virtually all aphids (Aphididae) harbor Buchnera aphidicola as an obligate endosymbiont to compensate nutritional deficiencies arising from their phloem diet. Many species within the Lachninae subfamily seem to be consistently associated also with Serratia symbiotica We have previously shown that both Cinara (Cinara) cedri and Cinara (Cupressobium) tujafilina (Lachninae: Eulachnini tribe) have indeed established co-obligate associations with both Buchnera and S. symbiotica However, while Buchnera genomes of both Cinara species are similar, genome degradation differs greatly between the two S. symbiotica strains. To gain insight into the essentiality and degree of integration of S. symbiotica within the Lachninae, we sequenced the genome of both Buchnera and S. symbiotica endosymbionts from the distantly related aphid Tuberolachnus salignus (Lachninae: Tuberolachnini tribe). We found a striking level of similarity between the endosymbiotic system of this aphid and that of C. cedri In both aphid hosts, S. symbiotica possesses a highly reduced genome and is found exclusively intracellularly inside bacteriocytes. Interestingly, T. salignus' endosymbionts present the same tryptophan biosynthetic metabolic complementation as C. cedri's, which is not present in C. tujafilina's. Moreover, we corroborate the riboflavin biosynthetic-role take-over/rescue by S. symbiotica in T. salignus, and therefore, provide further evidence for the previously proposed establishment of a secondary co-obligate endosymbiont in the common ancestor of the Lachninae aphids. Finally, we propose that the putative convergent split of the tryptophan biosynthetic role between Buchnera and S. symbiotica could be behind the establishment of S. symbiotica as an obligate intracellular symbiont and the triggering of further genome degradation. PMID- 27190009 TI - Dopamine D2 receptor gene variants and response to rasagiline in early Parkinson's disease: a pharmacogenetic study. AB - The treatment of early Parkinson's disease with dopaminergic agents remains the mainstay of symptomatic therapy for this incurable neurodegenerative disorder. However, clinical responses to dopaminergic drugs vary substantially from person to person due to individual-, drug- and disease-related factors that may in part be genetically determined. Using clinical data and DNA samples ascertained through the largest placebo-controlled clinical trial of the monoamine oxidase B inhibitor, rasagiline (ClinicalTrials.gov number, NCT00256204), we examined how polymorphisms in candidate genes associate with the clinical response to rasagiline in early Parkinson's disease. Variants in genes that express proteins involved in the pharmacokinetics and pharmacodynamics of rasagiline, and genes previously associated with the risk to develop Parkinson's disease were genotyped. The LifeTechnologies OpenArray NT genotyping platform and polymerase chain reaction-based methods were used to analyse 204 single nucleotide polymorphisms and five variable number tandem repeats from 30 candidate genes in 692 available DNA samples from this clinical trial. The peak symptomatic response to rasagiline, the rate of symptom progression, and their relation to genetic variation were examined controlling for placebo effects using general linear and mixed effects models, respectively. Single nucleotide polymorphisms, rs2283265 and rs1076560, in the dopamine D2 receptor gene (DRD2) were found to be significantly associated with a favourable peak response to rasagiline at 12 weeks in early Parkinson's disease after controlling for multiple testing. From a linear regression, the betas were 2.5 and 2.38, respectively, with false discovery rate-corrected P-values of 0.032. These polymorphisms were in high linkage disequilibrium with each other (r(2) = 0.96) meaning that the same clinical response signal was identified by each of them. No polymorphisms were associated with slowing the rate of worsening in Parkinson symptoms from Weeks 12 to 36 after correction for multiple testing. This is the largest and most comprehensive pharmacogenetics study to date examining clinical response to an anti-parkinsonian drug and the first to be conducted in patients with early stage Parkinson's disease receiving monotherapy. The results indicate a clinically meaningful benefit to rasagiline in terms of the magnitude of improvement in parkinsonian symptoms for those with the favourable response genotypes. Future work is needed to elucidate the specific mechanisms through which these DRD2 variants operate in modulating the function of the nigrostriatal dopaminergic system.media-1vid110.1093/brain/aww109_video_abstractaww109_video_abstract. PMID- 27190011 TI - C9orf72 mutations and the puzzle of cerebro-cerebellar network degeneration. PMID- 27190010 TI - Cyclooxygenase inhibition targets neurons to prevent early behavioural decline in Alzheimer's disease model mice. AB - Identifying preventive targets for Alzheimer's disease is a central challenge of modern medicine. Non-steroidal anti-inflammatory drugs, which inhibit the cyclooxygenase enzymes COX-1 and COX-2, reduce the risk of developing Alzheimer's disease in normal ageing populations. This preventive effect coincides with an extended preclinical phase that spans years to decades before onset of cognitive decline. In the brain, COX-2 is induced in neurons in response to excitatory synaptic activity and in glial cells in response to inflammation. To identify mechanisms underlying prevention of cognitive decline by anti-inflammatory drugs, we first identified an early object memory deficit in APPSwe-PS1DeltaE9 mice that preceded previously identified spatial memory deficits in this model. We modelled prevention of this memory deficit with ibuprofen, and found that ibuprofen prevented memory impairment without producing any measurable changes in amyloid beta accumulation or glial inflammation. Instead, ibuprofen modulated hippocampal gene expression in pathways involved in neuronal plasticity and increased levels of norepinephrine and dopamine. The gene most highly downregulated by ibuprofen was neuronal tryptophan 2,3-dioxygenase (Tdo2), which encodes an enzyme that metabolizes tryptophan to kynurenine. TDO2 expression was increased by neuronal COX-2 activity, and overexpression of hippocampal TDO2 produced behavioural deficits. Moreover, pharmacological TDO2 inhibition prevented behavioural deficits in APPSwe-PS1DeltaE9 mice. Taken together, these data demonstrate broad effects of cyclooxygenase inhibition on multiple neuronal pathways that counteract the neurotoxic effects of early accumulating amyloid-beta oligomers. PMID- 27190013 TI - Migraine with aura and risk of silent brain infarcts and white matter hyperintensities: an MRI study. AB - A small number of population-based studies reported an association between migraine with aura and risk of silent brain infarcts and white matter hyperintensities in females. We investigated these relations in a population based sample of female twins. We contacted female twins ages 30-60 years identified through the population-based Danish Twin Registry. Based on questionnaire responses, twins were invited to participate in a telephone-based interview conducted by physicians. Headache diagnoses were established according to the International Headache Society criteria. Cases with migraine with aura, their co-twins, and unrelated migraine-free twins (controls) were invited to a brain magnetic resonance imaging scan performed at a single centre. Brain scans were assessed for the presence of infarcts, and white matter hyperintensities (visual rating scales and volumetric analyses) blinded to headache diagnoses. Comparisons were based on 172 cases, 34 co-twins, and 139 control subjects. Compared with control subjects, cases did not differ with regard to frequency of silent brain infarcts (four cases versus one control), periventricular white matter hyperintensity scores [adjusted mean difference (95% confidence interval): -0.1 (-0.5 to 0.2)] or deep white matter hyperintensity scores [adjusted mean difference (95% confidence interval): 0.1 (-0.8 to 1.1)] assessed by Scheltens' scale. Cases had a slightly higher total white matter hyperintensity volume compared with controls [adjusted mean difference (95% confidence interval): 0.17 (-0.08 to 0.41) cm(3)] and a similar difference was present in analyses restricted to twin pairs discordant for migraine with aura [adjusted mean difference 0.21 (-0.20 to 0.63)], but these differences did not reach statistical significance. We found no evidence of an association between silent brain infarcts, white matter hyperintensities, and migraine with aura. PMID- 27190014 TI - Reply: SCA23 and prodynorphin: is it time for gene retraction? PMID- 27190012 TI - The human subthalamic nucleus encodes the subjective value of reward and the cost of effort during decision-making. AB - Adaptive behaviour entails the capacity to select actions as a function of their energy cost and expected value and the disruption of this faculty is now viewed as a possible cause of the symptoms of Parkinson's disease. Indirect evidence points to the involvement of the subthalamic nucleus-the most common target for deep brain stimulation in Parkinson's disease-in cost-benefit computation. However, this putative function appears at odds with the current view that the subthalamic nucleus is important for adjusting behaviour to conflict. Here we tested these contrasting hypotheses by recording the neuronal activity of the subthalamic nucleus of patients with Parkinson's disease during an effort-based decision task. Local field potentials were recorded from the subthalamic nucleus of 12 patients with advanced Parkinson's disease (mean age 63.8 years +/- 6.8; mean disease duration 9.4 years +/- 2.5) both OFF and ON levodopa while they had to decide whether to engage in an effort task based on the level of effort required and the value of the reward promised in return. The data were analysed using generalized linear mixed models and cluster-based permutation methods. Behaviourally, the probability of trial acceptance increased with the reward value and decreased with the required effort level. Dopamine replacement therapy increased the rate of acceptance for efforts associated with low rewards. When recording the subthalamic nucleus activity, we found a clear neural response to both reward and effort cues in the 1-10 Hz range. In addition these responses were informative of the subjective value of reward and level of effort rather than their actual quantities, such that they were predictive of the participant's decisions. OFF levodopa, this link with acceptance was weakened. Finally, we found that these responses did not index conflict, as they did not vary as a function of the distance from indifference in the acceptance decision. These findings show that low-frequency neuronal activity in the subthalamic nucleus may encode the information required to make cost-benefit comparisons, rather than signal conflict. The link between these neural responses and behaviour was stronger under dopamine replacement therapy. Our findings are consistent with the view that Parkinson's disease symptoms may be caused by a disruption of the processes involved in balancing the value of actions with their associated effort cost. PMID- 27190015 TI - SCA23 and prodynorphin: is it time for gene retraction? PMID- 27190018 TI - Reply: Role of cortico-pallidal connectivity in the pathophysiology of dystonia. PMID- 27190017 TI - CSF1R mosaicism in a family with hereditary diffuse leukoencephalopathy with spheroids. AB - Mutations in the colony stimulating factor 1 receptor (CSF1R) have recently been discovered as causal for hereditary diffuse leukoencephalopathy with axonal spheroids. We identified a novel, heterozygous missense mutation in CSF1R [c.1990G > A p.(E664K)] by exome sequencing in five members of a family with hereditary diffuse leukoencephalopathy with axonal spheroids. Three affected siblings had characteristic white matter abnormalities and presented with progressive neurological decline. In the fourth affected sibling, early progression halted after allogeneic haematopoietic stem cell transplantation from a related donor. Blood spot DNA from this subject displayed chimerism in CSF1R acquired after haematopoietic stem cell transplantation. Interestingly, both parents were unaffected but the mother's blood and saliva were mosaic for the CSF1R mutation. Our findings suggest that expression of wild-type CSF1R in some cells, whether achieved by mosaicism or chimerism, may confer benefit in hereditary diffuse leukoencephalopathy with axonal spheroids and suggest that haematopoietic stem cell transplantation might have a therapeutic role for this disorder. PMID- 27190016 TI - Corticolimbic anatomical characteristics predetermine risk for chronic pain. AB - SEE TRACEY DOI101093/BRAIN/AWW147 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Mechanisms of chronic pain remain poorly understood. We tracked brain properties in subacute back pain patients longitudinally for 3 years as they either recovered from or transitioned to chronic pain. Whole-brain comparisons indicated corticolimbic, but not pain-related circuitry, white matter connections predisposed patients to chronic pain. Intra-corticolimbic white matter connectivity analysis identified three segregated communities: dorsal medial prefrontal cortex-amygdala-accumbens, ventral medial prefrontal cortex-amygdala, and orbitofrontal cortex-amygdala-hippocampus. Higher incidence of white matter and functional connections within the dorsal medial prefrontal cortex-amygdala accumbens circuit, as well as smaller amygdala volume, represented independent risk factors, together accounting for 60% of the variance for pain persistence. Opioid gene polymorphisms and negative mood contributed indirectly through corticolimbic anatomical factors, to risk for chronic pain. Our results imply that persistence of chronic pain is predetermined by corticolimbic neuroanatomical factors. PMID- 27190019 TI - The migraine generator revisited: continuous scanning of the migraine cycle over 30 days and three spontaneous attacks. AB - Functional imaging using positron emission tomography and later functional magnetic resonance imaging revealed a particular brainstem area that is believed to be specifically activated in migraine during, but not outside of the attack, and consequently has been coined the 'migraine generator'. However, the pathophysiological concept behind this term is not undisputed and typical migraine premonitory symptoms such as fatigue and yawning, but also a typical association of attacks to circadian and menstrual cycles, all make the hypothalamus a possible regulating region of migraine attacks. Neuroimaging studies investigating native human migraine attacks however are scarce and for methodological but also clinical reasons there are currently no studies investigating the last 24 h before headache onset. Here we report a migraine patient who had magnetic resonance imaging every day for 30 days, always in the morning, to cover, using functional imaging, a whole month and three complete, untreated migraine attacks. We found that hypothalamic activity as a response to trigeminal nociceptive stimulation is altered during the 24 h prior to pain onset, i.e. increases towards the next migraine attack. More importantly, the hypothalamus shows altered functional coupling with the spinal trigeminal nuclei and the region of the migraine generator, i.e. the dorsal rostral pons during the preictal day and the pain phase of native human migraine attacks. These data suggest that although the brainstem is highly linked to the migraine biology, the real driver of attacks might be the functional changes in hypothalamo-brainstem connectivity. PMID- 27190020 TI - Microvascular alterations and the role of complement in dermatomyositis. AB - Different mechanisms have been proposed to explain the pathological basis of perifascicular muscle fibre atrophy in dermatomyositis. These include ischaemia due to immune-mediated microvascular injury, enhanced expression of type 1 interferon-induced gene transcripts in perifascicular capillaries and muscle fibres, and occlusion of larger perimysial blood vessels. Microvascular complement deposition is a feature of dermatomyositis pathology but the trigger for complement activation, the predominant complement pathway involved, or its role in the pathogenesis of the disease, has not been clearly defined. In the first step of this study we examined the density of capillaries and transverse vessels and searched for occlusion or depletion of larger perimysial blood vessels in 10 patients with dermatomyositis. This revealed an invariable association of perifascicular atrophy with capillary and transverse vessel depletion. The capillary and transverse vessel densities in non-atrophic fibre regions were not significantly different from those in muscle specimens of 10 age matched controls. Next, in the same 10, as well as in 40 additional dermatomyositis patients, we searched for vascular deposits of IgG, IgM, and the C5b-9 complement membrane attack complex. Thirty-one of 50 dermatomyositis specimens contained C5b-9 reactive endomysial microvessels but none of these or other vessels reacted for IgG. Ten of 50 specimens harboured IgM-positive capillaries but only a few of these reacted for C5b-9. Finally, we analysed and compared different pathways of complement activation in dermatomyositis, lupus nephritis, and necrotic muscle fibres in Duchenne dystrophy. In lupus nephritis, C5-b9 deposits co-localized with IgG, IgM, C1q, and C4d, consistent with immune complex dependent activation of the classical complement pathway. In both dermatomyositis and Duchenne dystrophy, C5-b9 deposits co-localized with C1q and C4d and rarely with IgM indicating activation of the classical complement pathway. We conclude that: perifascicular atrophy in dermatomyositis is consistently associated with focal microvascular depletion, and that microvascular membrane attack complex deposits in dermatomyositis result from activation of the classical complement pathway triggered by direct binding of C1q to injured endothelial cells. PMID- 27190021 TI - Universal and language-specific sublexical cues in speech perception: a novel electroencephalography-lesion approach. AB - SEE CAPPA DOI101093/BRAIN/AWW090 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE : The phonological structure of speech supports the highly automatic mapping of sound to meaning. While it is uncontroversial that phonotactic knowledge acts upon lexical access, it is unclear at what stage these combinatorial rules, governing phonological well-formedness in a given language, shape speech comprehension. Moreover few studies have investigated the neuronal network affording this important step in speech comprehension. Therefore we asked 70 participants-half of whom suffered from a chronic left hemispheric lesion-to listen to 252 different monosyllabic pseudowords. The material models universal preferences of phonotactic well-formedness by including naturally spoken pseudowords and digitally reversed exemplars. The latter partially violate phonological structure of all human speech and are rich in universally dispreferred phoneme sequences while preserving basic auditory parameters. Language-specific constraints were modelled in that half of the naturally spoken pseudowords complied with the phonotactics of the native language of the monolingual participants (German) while the other half did not. To ensure universal well-formedness and naturalness, the latter stimuli comply with Slovak phonotactics and all stimuli were produced by an early bilingual speaker. To maximally attenuate lexico-semantic influences, transparent pseudowords were avoided and participants had to detect immediate repetitions, a task orthogonal to the contrasts of interest. The results show that phonological 'well formedness' modulates implicit processing of speech at different levels: universally dispreferred phonological structure elicits early, medium and late latency differences in the evoked potential. On the contrary, the language specific phonotactic contrast selectively modulates a medium latency component of the event-related potentials around 400 ms. Using a novel event-related potential lesion approach allowed us to furthermore supply first evidence that implicit processing of these different phonotactic levels relies on partially separable brain areas in the left hemisphere: contrasting forward to reversed speech the approach delineated an area comprising supramarginal and angular gyri. Conversely, the contrast between legal versus illegal phonotactics consistently projected to anterior and middle portions of the middle temporal and superior temporal gyri. Our data support the notion that phonological structure acts on different stages of phonologically and lexically driven steps of speech comprehension. In the context of previous work we propose context-dependent sensitivity to different levels of phonotactic well-formedness. PMID- 27190022 TI - Migraine photophobia originating in cone-driven retinal pathways. AB - Migraine headache is uniquely exacerbated by light. Using psychophysical assessments in patients with normal eyesight we found that green light exacerbates migraine headache significantly less than white, blue, amber or red lights. To delineate mechanisms, we used electroretinography and visual evoked potential recording in patients, and multi-unit recording of dura- and light sensitive thalamic neurons in rats to show that green activates cone-driven retinal pathways to a lesser extent than white, blue and red; that thalamic neurons are most responsive to blue and least responsive to green; and that cortical responses to green are significantly smaller than those generated by blue, amber and red lights. These findings suggest that patients' experience with colour and migraine photophobia could originate in cone-driven retinal pathways, fine-tuned in relay thalamic neurons outside the main visual pathway, and preserved by the cortex. Additionally, the findings provide substrate for the soothing effects of green light. PMID- 27190024 TI - Role of cortico-pallidal connectivity in the pathophysiology of dystonia. PMID- 27190023 TI - In vivo imaging of neuromelanin in Parkinson's disease using 18F-AV-1451 PET. AB - The tau tangle ligand (18)F-AV-1451 ((18)F-T807) binds to neuromelanin in the midbrain, and may therefore be a measure of the pigmented dopaminergic neuronal count in the substantia nigra. Parkinson's disease is characterized by progressive loss of dopaminergic neurons. Extrapolation of post-mortem data predicts that a ~30% decline of nigral dopamine neurons is necessary to cause motor symptoms in Parkinson's disease. Putamen dopamine terminal loss at disease onset most likely exceeds that of the nigral cell bodies and has been estimated to be of the order of 50-70%. We investigated the utility of (18)F-AV-1451 positron emission tomography to visualize the concentration of nigral neuromelanin in Parkinson's disease and correlated the findings to dopamine transporter density, measured by (123)I-FP-CIT single photon emission computed tomography. A total of 17 patients with idiopathic Parkinson's disease and 16 age and sex-matched control subjects had (18)F-AV-1451 positron emission tomography using a Siemens high-resolution research tomograph. Twelve patients with Parkinson's disease also received a standardized (123)I-FP-CIT single photon emission computed tomography scan at our imaging facility. Many of the patients with Parkinson's disease displayed visually apparent decreased (18)F-AV-1451 signal in the midbrain. On quantitation, patients showed a 30% mean decrease in total nigral (18)F-AV-1451 volume of distribution compared with controls (P = 0.004), but there was an overlap of the individual ranges. We saw no significant correlation between symptom dominant side and contralateral nigral volume of distribution. There was no correlation between nigral (18)F-AV-1451 volume of distribution and age or time since diagnosis. In the subset of 12 patients, who also had a (123)I-FP-CIT scan, the mean total striatal dopamine transporter signal was decreased by 45% and the mean total (18)F-AV-1451 substantia nigra volume of distribution was decreased by 33% after median disease duration of 4.7 years (0.5-12.4 years). (18)F-AV-1451 positron emission tomography may be the first radiotracer to reflect the loss of pigmented neurons in the substantia nigra of parkinsonian patients. The magnitude of the nigral signal loss was smaller than the decrease in striatal dopamine transporter signal measured by dopamine transporter single photon emission computed tomography. These findings suggest a more severe loss of striatal nerve terminal function compared with neuronal cell bodies, in accordance with the post-mortem literature. PMID- 27190027 TI - A causal role for the anterior mid-cingulate cortex in negative affect and cognitive control. AB - Converging evidence has linked the anterior mid-cingulate cortex to negative affect, pain and cognitive control. It has previously been proposed that this region uses information about punishment to control aversively motivated actions. Studies on the effects of lesions allow causal inferences about brain function; however, naturally occurring lesions in the anterior mid-cingulate cortex are rare. In two studies we therefore recruited 94 volunteers, comprising 15 patients with treatment-resistant depression who had received bilateral anterior cingulotomy, which consists of lesions made within the anterior mid-cingulate cortex, 20 patients with treatment-resistant depression who had not received surgery and 59 healthy control subjects. Using the Ekman 60 faces paradigm and two Stroop paradigms, we tested the hypothesis that patients who received anterior cingulotomy were impaired in recognizing negative facial affect expressions but not positive or neutral facial expressions, and impaired in Stroop cognitive control, with larger lesions being associated with more impairment. Consistent with this hypothesis, we found that larger volume lesions predicted more impairment in recognizing fear, disgust and anger, and no impairment in recognizing facial expressions of surprise or happiness. However, we found no impairment in recognizing expressions of sadness. Also consistent with the hypothesis, we found that larger volume lesions predicted impaired Stroop cognitive control. Notably, this relationship was only present when anterior mid-cingulate cortex lesion volume was defined as the overlap between cingulotomy lesion volume and Shackman's meta-analysis-derived binary masks for negative affect and cognitive control. Given substantial evidence from healthy subjects that the anterior mid-cingulate cortex is part of a network associated with the experience of negative affect and pain, engaging cognitive control processes for optimizing behaviour in the presence of such stimuli, our findings support the assertion that this region has a causal role in these processes. While the clinical justification for cingulotomy is empirical and not theoretical, it is plausible that lesions within a brain region associated with the subjective experience of negative affect and pain may be therapeutic for patients with otherwise intractable mood, anxiety and pain syndromes. PMID- 27190025 TI - Thalamic pathology and memory loss in early Alzheimer's disease: moving the focus from the medial temporal lobe to Papez circuit. AB - It is widely assumed that incipient protein pathology in the medial temporal lobe instigates the loss of episodic memory in Alzheimer's disease, one of the earliest cognitive deficits in this type of dementia. Within this region, the hippocampus is seen as the most vital for episodic memory. Consequently, research into the causes of memory loss in Alzheimer's disease continues to centre on hippocampal dysfunction and how disease-modifying therapies in this region can potentially alleviate memory symptomology. The present review questions this entrenched notion by bringing together findings from post-mortem studies, non invasive imaging (including studies of presymptomatic, at-risk cases) and genetically modified animal models. The combined evidence indicates that the loss of episodic memory in early Alzheimer's disease reflects much wider neurodegeneration in an extended mnemonic system (Papez circuit), which critically involves the limbic thalamus. Within this system, the anterior thalamic nuclei are prominent, both for their vital contributions to episodic memory and for how these same nuclei appear vulnerable in prodromal Alzheimer's disease. As thalamic abnormalities occur in some of the earliest stages of the disease, the idea that such changes are merely secondary to medial temporal lobe dysfunctions is challenged. This alternate view is further strengthened by the interdependent relationship between the anterior thalamic nuclei and retrosplenial cortex, given how dysfunctions in the latter cortical area provide some of the earliest in vivo imaging evidence of prodromal Alzheimer's disease. Appreciating the importance of the anterior thalamic nuclei for memory and attention provides a more balanced understanding of Alzheimer's disease. Furthermore, this refocus on the limbic thalamus, as well as the rest of Papez circuit, would have significant implications for the diagnostics, modelling, and experimental treatment of cognitive symptoms in Alzheimer's disease. PMID- 27190029 TI - Reply: C9orf72 mutations and the puzzle of cerebro-cerebellar network degeneration. PMID- 27190028 TI - The unfolded protein response: mechanisms and therapy of neurodegeneration. AB - Activation of the unfolded protein response is emerging as a common theme in protein-misfolding neurodegenerative diseases, with relevant markers observed in patient tissue and mouse models. Genetic and pharmacological manipulation of the pathway in several mouse models has shown that this is not a passive consequence of the neurodegeneration process. Rather, overactivation of the protein kinase RNA-like ER kinase (PERK, encoded by EIF2AK3) branch of the unfolded protein response directly contributes to disease pathogenesis through the critical reduction in neuronal protein synthesis rates, essential for learning and memory and for neuronal survival. The pharmacological inhibition of this process in these models is strikingly neuroprotective, resulting in the discovery of the first small molecule preventing neurodegeneration and clinical disease in vivo This now represents a potential generic approach for boosting memory and preventing neurodegeneration across the spectrum of these disorders, albeit with some exceptions, independent of disease-specific proteins. Targeting the unfolded protein response, and particularly PERK-branch mediated translational failure is thus an increasingly compelling strategy for new treatments for dementia and neurodegenerative disease. PMID- 27190026 TI - MicroRNAs targeting TGFbeta signalling underlie the regulatory T cell defect in multiple sclerosis. AB - Transforming growth factor beta (TGFbeta) signalling is critical for regulatory T cell development and function, and regulatory T cell dysregulation is a common observation in autoimmune diseases, including multiple sclerosis. In a comprehensive miRNA profiling study of patients with multiple sclerosis naive CD4 T cells, 19 differentially expressed miRNAs predicted to target the TGFbeta signalling pathway were identified, leading to the hypothesis that miRNAs may be responsible for the regulatory T cell defect observed in patients with multiple sclerosis. Patients with multiple sclerosis had reduced levels of TGFbeta signalling components in their naive CD4 T cells. The differentially expressed miRNAs negatively regulated the TGFbeta pathway, resulting in a reduced capacity of naive CD4 T cells to differentiate into regulatory T cells. Interestingly, the limited number of regulatory T cells, that did develop when these TGFbeta targeting miRNAs were overexpressed, were capable of suppressing effector T cells. As it has previously been demonstrated that compromising TGFbeta signalling results in a reduced regulatory T cell repertoire insufficient to control autoimmunity, and patients with multiple sclerosis have a reduced regulatory T cell repertoire, these data indicate that the elevated expression of multiple TGFbeta-targeting miRNAs in naive CD4 T cells of patients with multiple sclerosis impairs TGFbeta signalling, and dampens regulatory T cell development, thereby enhancing susceptibility to developing multiple sclerosis. PMID- 27190031 TI - Of sex and determination: marking 25 years of Randy, the sex-reversed mouse. AB - On Thursday 9 May 1991, the world awoke to front-page news of a breakthrough in biological research. From Washington to Wollongong, newspapers, radio and TV were abuzz with the story of a transgenic mouse in London called Randy. Why was this mouse so special? The mouse in question was a chromosomal female (XX) made male by the presence of a transgene containing the Y chromosome gene Sry This sex reversal provided clear experimental proof that Sry was the elusive mammalian sex determining gene. Twenty-five years on, we reflect on what this discovery meant for our understanding of how males and females arise and what remains to be understood. PMID- 27190032 TI - Transcriptional interpretation of Shh morphogen signaling: computational modeling validates empirically established models. PMID- 27190030 TI - Emerging therapies for mitochondrial disorders. AB - Mitochondrial disorders are a diverse group of debilitating conditions resulting from nuclear and mitochondrial DNA mutations that affect multiple organs, often including the central and peripheral nervous system. Despite major advances in our understanding of the molecular mechanisms, effective treatments have not been forthcoming. For over five decades patients have been treated with different vitamins, co-factors and nutritional supplements, but with no proven benefit. There is therefore a clear need for a new approach. Several new strategies have been proposed acting at the molecular or cellular level. Whilst many show promise in vitro, the clinical potential of some is questionable. Here we critically appraise the most promising preclinical developments, placing the greatest emphasis on diseases caused by mitochondrial DNA mutations. With new animal and cellular models, longitudinal deep phenotyping in large patient cohorts, and growing interest from the pharmaceutical industry, the field is poised to make a breakthrough. PMID- 27190033 TI - Mathematical models help explain experimental data. Response to 'Transcriptional interpretation of Shh morphogen signaling: computational modeling validates empirically established models'. PMID- 27190034 TI - An overview of mammalian pluripotency. AB - Mammalian pluripotency is the ability to give rise to all somatic cells as well as the germ cells of an adult mammal. It is a unique feature of embryonic epiblast cells, existing only transiently, as cells pass through early developmental stages. By contrast, pluripotency can be captured and stabilized indefinitely in cell culture and can also be reactivated in differentiated cells via nuclear reprogramming. Pluripotent stem cells (PSCs) are the in vitro carriers of pluripotency and they can inhabit discrete pluripotent states depending on the stage at which they were derived and their culture conditions. Here, and in the accompanying poster, we provide a summary of mammalian pluripotency both in vivo and in vitro, and highlight recent and future applications of PSCs for basic and translational research. PMID- 27190035 TI - Neurogenesis in Cancun: where science meets the sea. AB - In March 2016, meeting organizers Sebastian Jessberger and Hongjun Song brought together over 100 scientists from around the world to Cancun, Mexico to present the latest research on neurogenesis. The meeting covered diverse aspects of embryonic and adult neurogenesis with a focus on novel technologies, including chemogenetics and optogenetics, live cell two-photon imaging, cell fate reprogramming and human pluripotent stem cell models. This Meeting Review describes the exciting work that was presented and some of the emerging themes from the meeting. PMID- 27190038 TI - Hypoxia promotes production of neural crest cells in the embryonic head. AB - Hypoxia is encountered in either pathological or physiological conditions, the latter of which is seen in amniote embryos prior to the commencement of a functional blood circulation. During the hypoxic stage, a large number of neural crest cells arise from the head neural tube by epithelial-to-mesenchymal transition (EMT). As EMT-like cancer dissemination can be promoted by hypoxia, we investigated whether hypoxia contributes to embryonic EMT. Using chick embryos, we show that the hypoxic cellular response, mediated by hypoxia-inducible factor (HIF)-1alpha, is required to produce a sufficient number of neural crest cells. Among the genes that are involved in neural crest cell development, some genes are more sensitive to hypoxia than others, demonstrating that the effect of hypoxia is gene specific. Once blood circulation becomes fully functional, the embryonic head no longer produces neural crest cells in vivo, despite the capability to do so in a hypoxia-mimicking condition in vitro, suggesting that the oxygen supply helps to stop emigration of neural crest cells in the head. These results highlight the importance of hypoxia in normal embryonic development. PMID- 27190036 TI - The transcriptional repressor Blimp1 is expressed in rare luminal progenitors and is essential for mammary gland development. AB - Mammary gland morphogenesis depends on a tight balance between cell proliferation, differentiation and apoptosis, to create a defined functional hierarchy within the epithelia. The limited availability of stem cell/progenitor markers has made it challenging to decipher lineage relationships. Here, we identify a rare subset of luminal progenitors that express the zinc finger transcriptional repressor Blimp1, and demonstrate that this subset of highly clonogenic luminal progenitors is required for mammary gland development. Conditional inactivation experiments using K14-Cre and WAPi-Cre deleter strains revealed essential functions at multiple developmental stages. Thus, Blimp1 regulates proliferation, apoptosis and alveolar cell maturation during puberty and pregnancy. Loss of Blimp1 disrupts epithelial architecture and lumen formation both in vivo and in three-dimensional (3D) primary cell cultures. Collectively, these results demonstrate that Blimp1 is required to maintain a highly proliferative luminal subset necessary for mammary gland development and homeostasis. PMID- 27190041 TI - The Joint Toxicity of Different Temperature Coefficient Insecticides on Apolygus lucorum (Hemiptera: Miridae). AB - The effect of temperature on the cotoxicity coefficient (CTC) value was used to evaluate mixture efficacy of different temperature coefficient chemicals from 15 to 35 degrees C by exposing third-instar Apolygus lucorum (Meyer-Dur) to dip treated asparagus bean pods. The results indicated the joint toxicity of same temperature coefficient insecticide (TCI) types were unaffected by temperature. This means that even when temperatures change, the mixture ratios of the highest CTC values remained the same, and the effect of temperature on the joint toxicity of same TCI types was only on the CTC values. However, the effect of temperature was variable when considering the joint toxicity of different TCI types. The effect of temperature on the joint toxicity of both strong positive and strong negative TCI types was clear, and the highest CTC values of mixture ratios changed with temperature regularly. When comparing the influence of temperature between strong/slight positive/negative insecticides, the results indicated a greater influence of the strong TCI. Paradoxically, the highest CTC value of the imidacloprid and methomyl mixture did not change with temperature changes consistently, even with the variance of imidacloprid ratios, a strong TCI. These results will guide pest managers in choosing the most effective insecticide mixtures for A. lucorum control under given environmental conditions. PMID- 27190037 TI - The ADP-ribose polymerase Tankyrase regulates adult intestinal stem cell proliferation during homeostasis in Drosophila. AB - Wnt/beta-catenin signaling controls intestinal stem cell (ISC) proliferation, and is aberrantly activated in colorectal cancer. Inhibitors of the ADP-ribose polymerase Tankyrase (Tnks) have become lead therapeutic candidates for Wnt driven cancers, following the recent discovery that Tnks targets Axin, a negative regulator of Wnt signaling, for proteolysis. Initial reports indicated that Tnks is important for Wnt pathway activation in cultured human cell lines. However, the requirement for Tnks in physiological settings has been less clear, as subsequent studies in mice, fish and flies suggested that Tnks was either entirely dispensable for Wnt-dependent processes in vivo, or alternatively, had tissue-specific roles. Here, using null alleles, we demonstrate that the regulation of Axin by the highly conserved Drosophila Tnks homolog is essential for the control of ISC proliferation. Furthermore, in the adult intestine, where activity of the Wingless pathway is graded and peaks at each compartmental boundary, Tnks is dispensable for signaling in regions where pathway activity is high, but essential where pathway activity is relatively low. Finally, as observed previously for Wingless pathway components, Tnks activity in absorptive enterocytes controls the proliferation of neighboring ISCs non-autonomously by regulating JAK/STAT signaling. These findings reveal the requirement for Tnks in the control of ISC proliferation and suggest an essential role in the amplification of Wnt signaling, with relevance for development, homeostasis and cancer. PMID- 27190042 TI - Western Corn Rootworm (Coleoptera: Chrysomelidae) Larval Movement in eCry3.1Ab+mCry3A Seed Blend Scenarios. AB - Corn fields planted with plant-incorporated Bacillus thuringiensis (Bt) proteins must have a portion of the field planted with non-Bt, isoline, plants that serve as a refuge for susceptible insects. In the Corn Belt, refuge seeds are now blended in the bag with Bt seeds for corn hybrids containing two or more toxins targeted toward the western corn rootworm, Diabrotica virgifera virgifera LeConte. Syngenta's corn hybrid, Agrisure Duracade, containing the eCry3.1Ab (event 5307) and mCry3a (event MIR604) rootworm-targeted toxins were registered as a seed blend in 2014. Western corn rootworm larval movement between the refuge plants and the Duracade plants was assessed to determine western corn rootworm survival and amount of root damage on these plants when planted in all possible seed blend scenarios. In this study, western corn rootworm larvae moved between isoline and Bt plants and adult survival was greater on Bt plants if movement from a neighboring infested isoline plant had occurred. However, root damage to these Bt plants did not reach economic levels. The low numbers of western corn rootworm larvae that did move from an infested Bt plant to an isoline plant could potentially select for resistance if they survived to adulthood. PMID- 27190043 TI - Molecular Cloning, Expression, and Identification of Bre Genes Involved in Glycosphingolipids Synthesis in Helicoverpa armigera (Lepidoptera: Noctuidae). AB - Glycosphingolipids (GSLs) play important roles in the cellular biology of vertebrate and invertebrate organisms, such as cell differentiation, tumor metastasis, and cell coordination. GSLs also serve as receptors for different bacterial toxins. For example, in the nematode Caenorhabditis elegans, GSLs function as receptors of the insecticidal Cry toxins produced by Bacillus thuringiensis (Bt), and mutations in bre genes involved in GSLs synthesis resulted in resistance to Cry5 toxin in this organism. However, the information of GSLs function in insects is still limited. In this study, three genes for glycosyltransferases, bre2, bre3, and bre4, from Helicoverpa armigera were identified and cloned. The previously reported bre5 gene from H. armigera was also analyzed. Protein sequence alignments revealed that proteins codified by H. armigera Bre shared high identity with homologous proteins from other organisms. Expression profile analysis revealed that the expressions of bre genes varied in the different tissues and also in the different developmental stages of H. armigera. Finally, the heterologous expression of bre genes in Trichoplusia ni Hi5 cell line showed that the corresponding translated proteins were localized in the cytoplasm of Hi5 cells. These results provide the bases for further functional studies of bre genes and analyzing potential roles of GSLs in mode of action of Cry1A toxin in H. armigera. PMID- 27190044 TI - All Things in Moderation: Prevention of Intestinal Adenomas by DNA Hypomethylation. AB - DNA hypomethylation can prevent intestinal tumorigenesis, presumably by reducing epigenetic silencing of tumor-suppressor genes. A study in this issue by Sheaffer and colleagues challenges this notion by showing that severe DNA hypomethylation by tissue-specific Dnmt1 knockout can actually promote intestinal adenoma formation. Cancer Prev Res; 9(7); 509-11. (c)2016 AACRSee related article by Sheaffer, et al., p. 534. PMID- 27190045 TI - Lifetime Number of Ovulatory Cycles and Risks of Ovarian and Endometrial Cancer Among Postmenopausal Women. AB - Previous studies have shown that a greater number of ovulatory cycles, cumulatively summed as lifetime number of ovulatory cycles (LOC), increases ovarian cancer risk, but there is no uniform algorithm with which to compute LOC. The association between LOC and endometrial cancer is less certain. Accordingly, we identified 14 different LOC algorithms in a literature review and calculated LOCs in the Polish Cancer Study (2001-2003). We evaluated the associations of LOC with ovarian and endometrial cancer risks using unconditional logistic regression, with and without adjustment for individual risk factors used in the LOC computations. Our analysis included 302 ovarian cancer cases with 1,356 controls and 532 endometrial cancer cases with 1,286 controls. We found a high correlation between LOC values among the combined controls (r >= 0.88) and identified 5 groups of similar LOC algorithms. A LOC value in the highest quartile was associated with ovarian cancer risk as computed by 2 algorithms (odds ratio (OR) = 2.22 (95% confidence interval (CI): 1.07, 4.62) and OR = 2.44 (95% CI: 1.22, 4.87)) and with endometrial cancer risk as computed by 1 algorithm (OR = 1.95, 95% CI: 1.11, 3.44). LOC algorithms using a core set of variables widely available in epidemiologic studies may be independently associated with risk of gynecological cancers beyond the contribution of the individual risk factors, such as ages at menopause and menarche. PMID- 27190050 TI - Phytohormone regulation of root growth triggered by P deficiency or Al toxicity. AB - Phosphorus (P) deficiency and aluminum (Al) toxicity often coexist and limit plant growth on acid soils. It has been well documented that both P deficiency and Al toxicity alter root growth, including inhibition of primary roots and promotion of lateral roots. This suggests that plants adapt to both stresses through a common regulation pathway. Although an expanding set of results shows that phytohormones play vital roles in controlling root responses to Pi starvation and Al toxicity, it remains largely unknown whether P and Al coordinately regulate root growth through interacting phytohormone biosynthesis and signal transduction pathways. This review provides a summary of recent results concerning the influences of P deficiency and Al toxicity on root growth through the action of phytohormones, most notably auxin and ethylene. The objective is to facilitate increasing insights into complex responses of plants to adverse factors common on acid soils, which can spur development of 'smart' cultivars with better root growth and higher yield on these globally distributed marginal soils. PMID- 27190055 TI - Myosin light chain phosphorylation, novel targets to repair a broken heart? PMID- 27190057 TI - Ocular Metabolism of Levobunolol: Historic and Emerging Metabolic Pathways. AB - Although ocular transport and delivery have been well studied, metabolism in the eye is not well documented, even for clinically available medications such as levobunolol, a potent and nonselective beta-adrenergic receptor antagonist. Recently, we reported an in vitro methodology that could be used to evaluate ocular metabolism across preclinical species and humans. The current investigation provides detailed in vitro ocular and liver metabolism of levobunolol in rat, rabbit, and human S9 fractions, including the formation of equipotent active metabolite, dihydrolevobunolol, with the help of high resolution mass spectrometry. 11 of the 16 metabolites of levobunolol identified herein, including a direct acetyl conjugate of levobunolol observed in all ocular and liver fractions, have not been reported in the literature. The study documents the identification of six human ocular metabolites that have never been reported. The current investigation presents evidence for ocular and hepatic metabolism of levobunolol via non-cytochrome P450 pathways, which have not been comprehensively investigated to date. Our results indicated that rat liver S9 and human ocular S9 fractions formed the most metabolites. Furthermore, liver was a poor in vitro surrogate for eye, and rat and rabbit were poor surrogates for human in terms of the rate and extent of levobunolol metabolism. PMID- 27190059 TI - Selective HDAC6 inhibition prevents TNF-alpha-induced lung endothelial cell barrier disruption and endotoxin-induced pulmonary edema. AB - Lung endothelial damage contributes to the pathogenesis of acute lung injury. New strategies against lung endothelial barrier dysfunction may provide therapeutic benefits against lung vascular injury. Cell-cell junctions and microtubule cytoskeleton are basic components in maintaining endothelial barrier integrity. HDAC6, a deacetylase primarily localized in the cytoplasm, has been reported to modulate nonnuclear protein function through deacetylation. Both alpha-tubulin and beta-catenin are substrates for HDAC6. Here, we examined the effects of tubastatin A, a highly selective HDAC6 inhibitor, on TNF-alpha induced lung endothelial cell barrier disruption and endotoxin-induced pulmonary edema. Selective HDAC6 inhibition by tubastatin A blocked TNF-alpha-induced lung endothelial cell hyperpermeability, which was associated with increased alpha tubulin acetylation and microtubule stability. Tubastatin A pretreatment inhibited TNF-alpha-induced endothelial cell contraction and actin stress fiber formation with reduced myosin light chain phosphorylation. Selective HDAC6 inhibition by tubastatin A also induced beta-catenin acetylation in human lung endothelial cells, which was associated with increased membrane localization of beta-catenin and stabilization of adherens junctions. HDAC6 knockdown by small interfering RNA also prevented TNF-alpha-induced barrier dysfunction and increased alpha-tubulin and beta-catenin acetylation in endothelial cells. Furthermore, in a mouse model of endotoxemia, tubastatin A was able to prevent endotoxin-induced deacetylation of alpha-tubulin and beta-catenin in lung tissues, which was associated with reduced pulmonary edema. Collectively, our data indicate that selective HDAC6 inhibition by tubastatin A is a potent approach against lung endothelial barrier dysfunction. PMID- 27190056 TI - Trimethylamine and Trimethylamine N-Oxide, a Flavin-Containing Monooxygenase 3 (FMO3)-Mediated Host-Microbiome Metabolic Axis Implicated in Health and Disease. AB - Flavin-containing monooxygenase 3 (FMO3) is known primarily as an enzyme involved in the metabolism of therapeutic drugs. On a daily basis, however, we are exposed to one of the most abundant substrates of the enzyme trimethylamine (TMA), which is released from various dietary components by the action of gut bacteria. FMO3 converts the odorous TMA to nonodorous TMA N-oxide (TMAO), which is excreted in urine. Impaired FMO3 activity gives rise to the inherited disorder primary trimethylaminuria (TMAU). Affected individuals cannot produce TMAO and, consequently, excrete large amounts of TMA. A dysbiosis in gut bacteria can give rise to secondary TMAU. Recently, there has been much interest in FMO3 and its catalytic product, TMAO, because TMAO has been implicated in various conditions affecting health, including cardiovascular disease, reverse cholesterol transport, and glucose and lipid homeostasis. In this review, we consider the dietary components that can give rise to TMA, the gut bacteria involved in the production of TMA from dietary precursors, the metabolic reactions by which bacteria produce and use TMA, and the enzymes that catalyze the reactions. Also included is information on bacteria that produce TMA in the oral cavity and vagina, two key microbiome niches that can influence health. Finally, we discuss the importance of the TMA/TMAO microbiome-host axis in health and disease, considering factors that affect bacterial production and host metabolism of TMA, the involvement of TMAO and FMO3 in disease, and the implications of the host microbiome axis for management of TMAU. PMID- 27190058 TI - ASIC1-mediated calcium entry stimulates NFATc3 nuclear translocation via PICK1 coupling in pulmonary arterial smooth muscle cells. AB - The development of chronic hypoxia (CH)-induced pulmonary hypertension is associated with increased pulmonary arterial smooth muscle cell (PASMC) Ca(2+) influx through acid-sensing ion channel-1 (ASIC1) and activation of the Ca(2+)/calcineurin-dependent transcription factor known as nuclear factor of activated T-cells isoform c3 (NFATc3). Whether Ca(2+) influx through ASIC1 contributes to NFATc3 activation in the pulmonary vasculature is unknown. Furthermore, both ASIC1 and calcineurin have been shown to interact with the scaffolding protein known as protein interacting with C kinase-1 (PICK1). In the present study, we tested the hypothesis that ASIC1 contributes to NFATc3 nuclear translocation in PASMC in a PICK1-dependent manner. Using both ASIC1 knockout (ASIC1(-/-)) mice and pharmacological inhibition of ASIC1, we demonstrate that ASIC1 contributes to CH-induced (1 wk at 380 mmHg) and endothelin-1 (ET-1) induced (10(-7) M) Ca(2+) responses and NFATc3 nuclear import in PASMC. The interaction between ASIC1/PICK1/calcineurin was shown using a Duolink in situ Proximity Ligation Assay. Inhibition of PICK1 by using FSC231 abolished ET-1 induced and ionomycin-induced NFATc3 nuclear import, but it did not alter ET-1 mediated Ca(2+) responses, suggesting that PICK1 acts downstream of Ca(2+) influx. The key findings of the present work are that 1) Ca(2+) influx through ASIC1 mediates CH- and ET-1-induced NFATc3 nuclear import and 2) the scaffolding protein PICK1 is necessary for NFATc3 nuclear import. Together, these data provide an essential link between CH-induced ASIC1-mediated Ca(2+) influx and activation of the NFATc3 transcription factor. Identification of this ASIC1/PICK1/NFATc3 signaling complex increases our understanding of the mechanisms contributing to the vascular remodeling and increased vascular contractility that are associated with CH-induced pulmonary hypertension. PMID- 27190060 TI - Cellular response of mucociliary differentiated primary bronchial epithelial cells to diesel exhaust. AB - Diesel emissions are the main source of air pollution in urban areas, and diesel exposure is linked with substantial adverse health effects. In vitro diesel exposure models are considered a suitable tool for understanding these effects. Here we aimed to use a controlled in vitro exposure system to whole diesel exhaust to study the effect of whole diesel exhaust concentration and exposure duration on mucociliary differentiated human primary bronchial epithelial cells (PBEC). PBEC cultured at the air-liquid interface were exposed for 60 to 375 min to three different dilutions of diesel exhaust (DE). The DE mixture was generated by an engine at 47% load, and characterized for particulate matter size and distribution and chemical and gas composition. Cytotoxicity and epithelial barrier function was assessed, as well as mRNA expression and protein release analysis. DE caused a significant dose-dependent increase in expression of oxidative stress markers (HMOX1 and NQO1; n = 4) at 6 h after 150 min exposure. Furthermore, DE significantly increased the expression of the markers of the integrated stress response CHOP and GADD34 and of the proinflammatory chemokine CXCL8, as well as release of CXCL8 protein. Cytotoxic effects or effects on epithelial barrier function were observed only after prolonged exposures to the highest DE dose. These results demonstrate the suitability of our model and that exposure dose and duration and time of analysis postexposure are main determinants for the effects of DE on differentiated primary human airway epithelial cells. PMID- 27190061 TI - Reduced force of diaphragm muscle fibers in patients with chronic thromboembolic pulmonary hypertension. AB - Patients with pulmonary hypertension (PH) suffer from inspiratory muscle weakness. However, the pathophysiology of inspiratory muscle dysfunction in PH is unknown. We hypothesized that weakness of the diaphragm, the main inspiratory muscle, is an important contributor to inspiratory muscle dysfunction in PH patients. Our objective was to combine ex vivo diaphragm muscle fiber contractility measurements with measures of in vivo inspiratory muscle function in chronic thromboembolic pulmonary hypertension (CTEPH) patients. To assess diaphragm muscle contractility, function was studied in vivo by maximum inspiratory pressure (MIP) and ex vivo in diaphragm biopsies of the same CTEPH patients (N = 13) obtained during pulmonary endarterectomy. Patients undergoing elective lung surgery served as controls (N = 15). Muscle fiber cross-sectional area (CSA) was determined in cryosections and contractility in permeabilized muscle fibers. Diaphragm muscle fiber CSA was not significantly different between control and CTEPH patients in both slow-twitch and fast-twitch fibers. Maximal force-generating capacity was significantly lower in slow-twitch muscle fibers of CTEPH patients, whereas no difference was observed in fast-twitch muscle fibers. The maximal force of diaphragm muscle fibers correlated significantly with MIP. The calcium sensitivity of force generation was significantly reduced in fast twitch muscle fibers of CTEPH patients, resulting in a ~40% reduction of submaximal force generation. The fast skeletal troponin activator CK-2066260 (5 MUM) restored submaximal force generation to levels exceeding those observed in control subjects. In conclusion, diaphragm muscle fiber contractility is hampered in CTEPH patients and contributes to the reduced function of the inspiratory muscles in CTEPH patients. PMID- 27190062 TI - beta2-Adrenergic agonists attenuate organic dust-induced lung inflammation. AB - Agricultural dust exposure results in significant lung inflammation, and individuals working in concentrated animal feeding operations (CAFOs) are at risk for chronic airway inflammatory diseases. Exposure of bronchial epithelial cells to aqueous extracts of hog CAFO dusts (HDE) leads to inflammatory cytokine production that is driven by protein kinase C (PKC) activation. cAMP-dependent protein kinase (PKA)-activating agents can inhibit PKC activation in epithelial cells, leading to reduced inflammatory cytokine production following HDE exposure. beta2-Adrenergic receptor agonists (beta2-agonists) activate PKA, and we hypothesized that beta2-agonists would beneficially impact HDE-induced adverse airway inflammatory consequences. Bronchial epithelial cells were cultured with the short-acting beta2-agonist salbutamol or the long-acting beta2-agonist salmeterol prior to stimulation with HDE. beta2-Agonist treatment significantly increased PKA activation and significantly decreased HDE-stimulated IL-6 and IL-8 production in a concentration- and time-dependent manner. Salbutamol treatment significantly reduced HDE-induced intracellular adhesion molecule-1 expression and neutrophil adhesion to epithelial cells. Using an established intranasal inhalation exposure model, we found that salbutamol pretreatment reduced airway neutrophil influx and IL-6, TNF-alpha, CXCL1, and CXCL2 release in bronchoalveolar lavage fluid following a one-time exposure to HDE. Likewise, when mice were pretreated daily with salbutamol prior to HDE exposure for 3 wk, HDE induced neutrophil influx and inflammatory mediator production were also reduced. The severity of HDE-induced lung pathology in mice repetitively exposed to HDE for 3 wk was also decreased with daily salbutamol pretreatment. Together, these results support the need for future clinical investigations to evaluate the utility of beta2-agonist therapies in the treatment of airway inflammation associated with CAFO dust exposure. PMID- 27190063 TI - Selective and inducible targeting of CD11b+ mononuclear phagocytes in the murine lung with hCD68-rtTA transgenic systems. AB - During homeostasis two distinct macrophage (Mo) populations inhabit the lungs: tissue Mo (often called interstitial Mo) and resident alveolar Mo (resAMo). During acute lung inflammation, monocytes from the circulation migrate to areas of injury where they mature into a third Mo population: recruited Mo. Resident AMo uniquely express low levels of CD11b and high levels of CD11c. In comparison, recruited Mo and tissue Mo express high levels of CD11b and low levels of CD11c. It is likely that these three Mo subpopulations play distinct roles in injury and disease states; however, tools with which to individually target or track these populations are lacking. Here we demonstrate the utility of an hCD68-rtTA transgenic system for specific, robust, and inducible targeting of CD11b(+) recruited Mo and tissue Mo in the murine lung with negligible activation in resAMo. Using hCD68rtTA-GFP reporter mice, we show both during homeostasis and inflammation that administration of doxycycline induces tet-On reporter expression in recruited Mo and tissue Mo but not in resident AMo. We further demonstrate how hCD68-rtTA can be effectively combined with tet-On Cre to target these same recMo and tissue Mo. Accordingly, the hCD68-rtTA system is a powerful new tool that can be used for lineage tracing, fate mapping, and gene deletion in a variety of murine models, thereby enabling sophisticated investigation of the unique role of these CD11b(+) Mo during lung heath and disease. PMID- 27190066 TI - Macrophage migration inhibitory factor, a role in COPD. AB - Macrophage migration inhibitor factor (MIF) is a pluripotent cytokine associated with several different inflammatory conditions, but its role within lung inflammation and chronic obstructive pulmonary disease (COPD) is unclear. This study aimed to examine MIF in both stable COPD and during acute exacerbations (AECOPD). The study included 433 patients with COPD aged 41-76 and 325 individuals from the Bergen COPD cohort study who served as controls. All patients had an FEV1 of <80% predicted, FEV1/FVC ratio of <0.7, and a smoking history >10 pack-years. Serum levels of MIF were compared between the two groups at baseline, and for 149 patients, measurements were also carried out during AECOPD. Linear regression models were fitted with MIF as the outcome variable and adjusted for sex, age, body composition, smoking, and Charlson Comorbidity Score (CCS). Median MIF (interquartile range) in patients with COPD was 20.1 ng/ml (13.5-30.9) compared with 14.9 ng/ml (11.1-21.6) in controls (P < 0.01). MIF was bivariately associated with sex, body composition, and CCS (P < 0.05 for all). In the regression analyses, MIF was significantly higher in patients with COPD, coefficient 1.32 (P < 0.01) and 1.30 (P < 0.01) unadjusted and adjusted, respectively. In addition, in 149 patients during episodes of AECOPD, MIF was significantly elevated, with a median of 23.2 ng/ml (14.1-42.3) compared with measurements at stable disease of 19.3 ng/ml (12.4-31.3, P < 0.01). Serum levels of MIF were significantly higher in patients with COPD compared with controls. We also identified an additional increase in MIF levels during episodes of AECOPD. PMID- 27190064 TI - BMP signaling is essential in neonatal surfactant production during respiratory adaptation. AB - Deficiency in pulmonary surfactant results in neonatal respiratory distress, and the known genetic mutations in key components of surfactant only account for a small number of cases. Therefore, determining the regulatory mechanisms of surfactant production and secretion, particularly during the transition from prenatal to neonatal stages, is essential for better understanding of the pathogenesis of human neonatal respiratory distress. We have observed significant increase of bone morphogenetic protein (BMP) signaling in neonatal mouse lungs immediately after birth. Using genetically manipulated mice, we then studied the relationship between BMP signaling and surfactant production in neonates. Blockade of endogenous BMP signaling by deleting Bmpr1a (Alk3) or Smad1 in embryonic day 18.5 in perinatal lung epithelial cells resulted in severe neonatal respiratory distress and death, accompanied by atelectasis in histopathology and significant reductions of surfactant protein B and C, as well as Abca3, whereas prenatal lung development was not significantly affected. We then identified a new BMP-Smad1 downstream target, Nfatc3, which is known as an important transcription activator for surfactant proteins and Abca3. Furthermore, activation of BMP signaling in cultured lung epithelial cells was able to promote endogenous Nfatc3 expression and also stimulate the activity of an Nfatc3 promoter that contains a Smad1-binding site. Therefore, our study suggests that the BMP-Alk3-Smad1-Nfatc3 regulatory loop plays an important role in enhancing surfactant production in neonates, possibly helping neonatal respiratory adaptation from prenatal amniotic fluid environment to neonatal air breathing. PMID- 27190065 TI - Early coagulation events induce acute lung injury in a rat model of blunt traumatic brain injury. AB - Acute lung injury (ALI) and systemic coagulopathy are serious complications of traumatic brain injury (TBI) that frequently lead to poor clinical outcomes. Although the release of tissue factor (TF), a potent initiator of the extrinsic pathway of coagulation, from the injured brain is thought to play a key role in coagulopathy after TBI, its function in ALI following TBI remains unclear. In this study, we investigated whether the systemic appearance of TF correlated with the ensuing coagulopathy that follows TBI in ALI using an anesthetized rat blunt trauma TBI model. Blood and lung samples were obtained after TBI. Compared with controls, pulmonary edema and increased pulmonary permeability were observed as early as 5 min after TBI without evidence of norepinephrine involvement. Systemic TF increased at 5 min and then diminished 60 min after TBI. Lung injury and alveolar hemorrhaging were also observed as early as 5 min after TBI. A biphasic elevation of TF was observed in the lungs after TBI, and TF-positive microparticles (MPs) were detected in the alveolar spaces. Fibrin(ogen) deposition was also observed in the lungs within 60 min after TBI. Additionally, preadministration of a direct thrombin inhibitor, Refludan, attenuated lung injuries, thus implicating thrombin as a direct participant in ALI after TBI. The results from this study demonstrated that enhanced systemic TF may be an initiator of coagulation activation that contributes to ALI after TBI. PMID- 27190068 TI - The Economic Impact of Acetabular Labral Tears: A Cost-effectiveness Analysis Comparing Hip Arthroscopic Surgery and Structured Rehabilitation Alone in Patients Without Osteoarthritis. AB - BACKGROUND: Hip arthroscopic surgery has emerged as a successful procedure to manage acetabular labral tears and concurrent hip injuries, which if left untreated, may contribute to hip osteoarthritis (OA). Therefore, it is essential to analyze the economic impact of this treatment option. PURPOSE: To investigate the cost-effectiveness of hip arthroscopic surgery versus structured rehabilitation alone for acetabular labral tears, to examine the effects of age on cost-effectiveness, and to estimate the rate of symptomatic OA and total hip arthroplasty (THA) in both treatment arms over a lifetime horizon. STUDY DESIGN: Economic and decision analysis; Level of evidence, 2. METHODS: A cost effectiveness analysis of hip arthroscopic surgery compared with structured rehabilitation for symptomatic labral tears was performed using a Markov decision model constructed over a lifetime horizon. It was assumed that patients did not have OA. Direct costs (in 2014 United States dollars), utilities of health states (in quality-adjusted life years [QALYs] gained), and probabilities of transitioning between health states were estimated from a comprehensive literature review. Costs were estimated using national averages of Medicare reimbursements, adjusted for all payers in the United States from a societal perspective. Utilities were estimated from the Harris Hip Score. Cost effectiveness was assessed using the incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were performed to determine the effect of uncertainty on the model outcomes. RESULTS: For a cohort representative of patients undergoing hip arthroscopic surgery at our facility, arthroscopic surgery was more costly (additional $2653) but generated more utility (additional 3.94 QALYs) compared with rehabilitation over a lifetime. The mean ICER was $754/QALY, well below the conventional willingness to pay of $50,000/QALY. Arthroscopic surgery was cost-effective for 94.5% of patients. Although arthroscopic surgery decreased in cost-effectiveness with increasing age, arthroscopic surgery remained more cost-effective than rehabilitation for patients in the second to seventh decades of life. The lifetime incidence of symptomatic hip OA was over twice as high for patients treated with rehabilitation compared with arthroscopic surgery. The preferred treatment was sensitive to the utility after successful hip arthroscopic surgery, although the utility at which arthroscopic surgery becomes less cost-effective than rehabilitation is far below our best estimate. For older patients, the lifetime cost of arthroscopic surgery was greater, while the lifetime utility of arthroscopic surgery was less, approaching that of the rehabilitation arm. CONCLUSION: Hip arthroscopic surgery is more cost-effective and results in a considerably lower incidence of symptomatic OA than structured rehabilitation alone in treating symptomatic labral tears of patients in the second to seventh decades of life without pre-existing OA. PMID- 27190067 TI - Regional lung response to bronchodilator reversibility testing determined by electrical impedance tomography in chronic obstructive pulmonary disease. AB - Patients with obstructive lung diseases commonly undergo bronchodilator reversibility testing during examination of their pulmonary function by spirometry. A positive response is defined by an increase in forced expiratory volume in 1 s (FEV1). FEV1 is a rather nonspecific criterion not allowing the regional effects of bronchodilator to be assessed. We employed the imaging technique of electrical impedance tomography (EIT) to visualize the spatial and temporal ventilation distribution in 35 patients with chronic obstructive pulmonary disease at baseline and 5, 10, and 20 min after bronchodilator inhalation. EIT scanning was performed during tidal breathing and forced full expiration maneuver in parallel with spirometry. Ventilation distribution was determined by EIT by calculating the image pixel values of FEV1, forced vital capacity (FVC), tidal volume, peak flow, and mean forced expiratory flow between 25 and 75% of FVC. The global inhomogeneity indexes of each measure and histograms of pixel FEV1/FVC values were then determined to assess the bronchodilator effect on spatial ventilation distribution. Temporal ventilation distribution was analyzed from pixel values of times needed to exhale 75 and 90% of pixel FVC. Based on spirometric FEV1, significant bronchodilator response was found in 17 patients. These patients exhibited higher postbronchodilator values of all regional EIT-derived lung function measures in contrast to nonresponders. Ventilation distribution was inhomogeneous in both groups. Significant improvements were noted for spatial distribution of pixel FEV1 and tidal volume and temporal distribution in responders. By providing regional data, EIT might increase the diagnostic and prognostic information derived from reversibility testing. PMID- 27190070 TI - Erratum: Safety of percutaneous endoscopic gastrostomy tube placement in patients with continuous-flow ventricular assist devices. PMID- 27190069 TI - Incidence, Degree, and Clinical Effect of Subchondral Bone Overgrowth After Microfracture in the Knee. AB - BACKGROUND: Subchondral bone overgrowth has been described with variable frequency after microfracture, but little systematic information is available about the clinical incidence, risk factors, or clinical relevance of this phenomenon. HYPOTHESIS: Subchondral overgrowth (1) occurs with high incidence and various degrees after microfracture, (2) is associated with risk factors, and (3) affects clinical outcome score and failure rate. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A total of 84 patients undergoing microfracture in the knee were prospectively followed up to 6 years postoperatively through use of cartilage-sensitive magnetic resonance imaging to detect the incidence of subchondral bone overgrowth. The quantity of the overgrowth was graded systematically and was then correlated to patient and lesion characteristics, surgical technique, validated functional outcome scores, and failure rate. RESULTS: Subchondral bone overgrowth was observed in 62% of patients at a mean of 22 months after surgery. Most bone overgrowth (64%) was low grade and developed during the first 12 months after microfracture. Risk factors for bone overgrowth included high body mass index, defects on the lateral femoral condyle, and aggressive debridement of the calcified cartilage layer. Knee injury and Osteoarthritis Outcome Score results were not significantly different between patients with or without subchondral bone overgrowth. However, 93% of patients who failed microfracture demonstrated osseous overgrowth, and patients with osseous overgrowth showed a significantly higher failure rate (25%) than patients without overgrowth (3.1%; P < .01). CONCLUSION: Subchondral bone overgrowth is frequently observed after microfracture surgery but is mostly of low grade. Several risk factors were identified that can affect the incidence of this phenomenon. Importantly, subchondral overgrowth is associated with an increased rate of postoperative failure after microfracture. PMID- 27190072 TI - Efficiency of Respirator Filter Media against Diesel Particulate Matter: A Comparison Study Using Two Diesel Particulate Sources. AB - Diesel engines have been a mainstay within many industries since the early 1900s. Exposure to diesel particulate matter (DPM) is a major issue in many industrial workplaces given the potential for serious health impacts to exposed workers; including the potential for lung cancer and adverse irritant and cardiovascular effects. Personal respiratory protective devices are an accepted safety measure to mitigate worker exposure against the potentially damaging health impacts of DPM. To be protective, they need to act as effective filters against carbon and other particulates. In Australia, the filtering efficiency of respiratory protective devices is determined by challenging test filter media with aerosolised sodium chloride to determine penetration at designated flow rates. The methodology outlined in AS/NZS1716 (Standards Australia International Ltd and Standards New Zealand 2012. Respiratory protective devices. Sydney/Wellington: SAI Global Limited/Standards New Zealand) does not account for the differences between characteristics of workplace contaminants like DPM and sodium chloride such as structure, composition, and particle size. This study examined filtering efficiency for three commonly used AS/NZS certified respirator filter models, challenging them with two types of diesel emissions; those from a diesel generator and a diesel engine. Penetration through the filter media of elemental carbon (EC), total carbon (TC), and total suspended particulate (TSP) was calculated. Results indicate that filtering efficiency assumed by P2 certification in Australia was achieved for two of the three respirator models for DPM generated using the small diesel generator, whilst when the larger diesel engine was used, filtering efficiency requirements were met for all three filter models. These results suggest that the testing methodology specified for certification of personal respiratory protective devices by Standards Australia may not ensure adequate protection for respirator users against DPM under all circumstances of diesel generated particles. PMID- 27190071 TI - The relation among aldosterone, galectin-3, and myocardial fibrosis: a prospective clinical pilot follow-up study. AB - Primary aldosteronism has been associated with myocardial fibrosis, and is the most common cause of secondary hypertension. We previously showed that aldosterone can induce the secretion of galectin-3. The aim of this study was to investigate the association between myocardial fibrosis and plasma galectin-3 level in patients with primary aldosteronism. We prospectively analyzed 11 patients with aldosterone-producing adenoma (APA) who received adrenalectomy from December 2006 to October 2008, and 17 patients with essential hypertension as controls. Levels of plasma galectin-3 were determined in both groups, and both groups underwent echocardiography with cyclic variations of integrated backscatter (CVIBS) to characterize tissue initially and 1 year after surgery in the APA group. Diastolic blood pressure, concentration of plasma aldosterone and aldosterone-renin ratio were significantly higher, and serum potassium level and plasma renin activity significantly lower in the APA group compared to the controls. In addition, left ventricular mass index was significantly higher and CVIBS significantly lower in the APA group (7.3+/-2.0 vs 9.2+/-1.7 dB, p=0.015). Furthermore, the concentration of plasma galectin-3 was significantly higher in the APA group (2.1+/-0.9 vs 1.1+/-0.6 ng/mL, p=0.005) compared to the controls. CVIBS was correlated to plasma galectin-3 level. In the APA group, CVIBS increased significantly (7.3+/-2.0 to 9.2+/-2.4 dB, p=0.032) and plasma galectin 3 decreased (2.1+/-0.9 to 1.2+/-0.6, p=0.049) 1 year postadrenalectomy. The patients with APA had increased myocardial fibrosis, and this was associated with a higher plasma galectin-3 level. Both increased myocardial fibrosis and plasma galectin-3 level recovered at least partially after adrenalectomy. TRIAL REGISTRATION NUMBER: 200611031R; Results. PMID- 27190074 TI - News Feature: Better models for brain disease. PMID- 27190076 TI - Expectant management with close monitoring of mother and neonate should be practised after late preterm prelabour rupture of membranes. PMID- 27190077 TI - Restarting oral anticoagulation among patients with atrial fibrillation with gastrointestinal bleeding was associated with lower risk of all-cause mortality and thromboembolism. PMID- 27190078 TI - Serum advanced glycation endproducts are associated with left ventricular dysfunction in normal glucose metabolism but not in type 2 diabetes: The Hoorn Study. AB - OBJECTIVE: To investigate whether serum advanced glycation endproducts are associated with left ventricular systolic and diastolic function in participants with normal glucose metabolism, impaired glucose metabolism and type 2 diabetes mellitus. METHODS: Participants from a cross-sectional, population-based study (n = 280 with normal glucose metabolism, n = 171 with impaired glucose metabolism, n = 242 with type 2 diabetes mellitus) underwent echocardiography. Serum protein bound advanced glycation endproducts [i.e. Nepsilon-(carboxymethyl)lysine, pentosidine and Nepsilon-(carboxyethyl)lysine] were measured. Linear regression analyses were used and stratified according to glucose metabolism status. RESULTS: In normal glucose metabolism, higher Nepsilon-(carboxymethyl)lysine and pentosidine levels were associated with worse diastolic function (left atrial volume index and left atrial volume * left ventricular mass index product term) and higher Nepsilon-(carboxymethyl)lysine and Nepsilon-(carboxyethyl)lysine levels with worse systolic function (ejection fraction). In impaired glucose metabolism, a similar pattern emerged, though less consistent. In type 2 diabetes mellitus, these associations were non-existent for diastolic function or even reversed for systolic function. CONCLUSION: This suggests that serum advanced glycation endproducts are associated with impaired left ventricular function in normal glucose metabolism, but that with deteriorating glucose metabolism status, serum advanced glycation endproducts may not mirror heart failure risk. PMID- 27190079 TI - Central arterial stiffness is associated with systemic inflammation among Asians with type 2 diabetes. AB - OBJECTIVE: To examine the relationship between inflammation and central arterial stiffness in a type 2 diabetes Asian cohort. METHOD: Central arterial stiffness was estimated by carotid-femoral pulse wave velocity and augmentation index. Linear regression model was used to evaluate the association of high-sensitivity C-reactive protein and soluble receptor for advanced glycation end products with pulse wave velocity and augmentation index. High-sensitivity C-reactive protein was analysed as a continuous variable and categories (<1, 1-3, and >3 mg/L). RESULTS: There is no association between high-sensitivity C-reactive protein and pulse wave velocity. Augmentation index increased with high-sensitivity C reactive protein as a continuous variable (beta = 0.328, p = 0.049) and categories (beta = 1.474, p = 0.008 for high-sensitivity C-reactive protein: 1-3 mg/L and beta = 1.323, p = 0.019 for high-sensitivity C-reactive protein: >3 mg/L) after multivariable adjustment. No association was observed between augmentation index and soluble receptor for advanced glycation end products. Each unit increase in natural log-transformed soluble receptor for advanced glycation end products was associated with 0.328 m/s decrease in pulse wave velocity after multivariable adjustment (p = 0.007). CONCLUSION: Elevated high-sensitivity C reactive protein and decreased soluble receptor for advanced glycation end products are associated with augmentation index and pulse wave velocity, respectively, suggesting the potential role of systemic inflammation in the pathogenesis of central arterial stiffness in type 2 diabetes. PMID- 27190080 TI - Considerably decreased risk of cardiovascular disease with combined reductions in HbA1c, blood pressure and blood lipids in type 2 diabetes: Report from the Swedish National Diabetes Register. AB - OBJECTIVES: Assess the effect of risk factors changes on risk for cardiovascular disease and mortality in patients with type 2 diabetes selected from the Swedish National Diabetes Register. METHODS: Observational study of 13,477 females and males aged 30-75 years, with baseline HbA1c 41-67 mmol/mol, systolic blood pressure 122-154 mmHg and ratio non-HDL:HDL 1.7-4.1, followed for mean 6.5 years until 2012. Four groups were created: a reference group (n = 6757) with increasing final versus baseline HbA1c, systolic blood pressure and non-HDL:HDL cholesterol during the study period, and three groups with decreasing HbA1c (n = 1925), HbA1c and systolic blood pressure (n = 2050) or HbA1c and systolic blood pressure and non-HDL:HDL (n = 2745). RESULTS: Relative risk reduction for fatal/nonfatal cardiovascular disease was 35% with decrease in HbA1c only (mean 6 to final 49 mmol/mol), 56% with decrease in HbA1c and systolic blood pressure (mean 12 to final 128 mmHg) and 75% with combined decreases in HbA1c, systolic blood pressure and non-HDL:HDL (mean 0.8 to final 2.1), all p < 0.001 adjusting for clinical characteristics, other risk factors, treatments and previous cardiovascular disease. Similar risk reductions were found for fatal/nonfatal coronary heart disease, fatal cardiovascular disease, all-cause mortality and also in a subgroup of 3038 patients with albuminuria. CONCLUSION: Considerable risk reductions for cardiovascular disease and mortality were seen with combined long-term risk factor improvement. PMID- 27190082 TI - Early myocardial impairment in type 1 diabetes patients without known heart disease assessed with tissue Doppler echocardiography: The Thousand & 1 study. AB - PURPOSE: Cardiovascular disease is the most common cause of mortality in type 1 diabetes; patients with albuminuria are at greatest risk. We investigated myocardial function and premature myocardial impairment in type 1 diabetes patients with and without albuminuria compared to controls. METHODS: This study included a cross-sectional survey of 1093 type 1 diabetes patients from Steno Diabetes Center and 200 healthy controls. Conventional and tissue Doppler echocardiographic measurements were analysed in multivariable models in normoalbuminuria (n = 760), microalbuminuria (n = 227) and macroalbuminuria (n = 106). Investigators were blinded to degree of albuminuria. RESULTS: For the type 1 diabetes patients, mean age was 49.6 years, 53% were men and mean diabetes duration was 25.5 years. In multivariable models systolic velocity s' did not differ between type 1 diabetes patients with normoalbuminuria and controls (beta coefficient [95% confidence interval]: -0.17 [-0.41; 0.08], p = 0.19), but was impaired between controls and microalbuminuria (-0.53 [-0.84; -0.23], p = 0.001) and macroalbuminuria (-0.59 [-0.96; -0.22], p = 0.002). Diastolic measurements (e', a', e'/a', and E/e') were all significantly impaired in type 1 diabetes, for example, e'/a': normoalbuminuria, microalbuminuria and macroalbuminuria versus controls: -0.38 [-0.52; -0.23], p < 0.001; -0.49 [-0.67; -0.32], p < 0.001; and 0.81 [-1.03; -0.59], p < 0.001. In age-related analyses, myocardial impairment occurred prematurely in type 1 diabetes compared to controls (e.g. E/e' = 8; 9.2 years [normoalbuminuria], 17.3 years [microalbuminuria] and 41.4 years [macroalbuminuria] prematurely, respectively). CONCLUSION: In type 1 diabetes patients with albuminuria, both systolic and diastolic functions are impaired, whereas in patients without albuminuria only diastolic function is affected. Myocardial impairment is detectable many years prematurely in type 1 diabetes, especially in patients with albuminuria. PMID- 27190081 TI - Risk stratification for 25-year cardiovascular disease incidence in type 1 diabetes: Tree-structured survival analysis of the Pittsburgh Epidemiology of Diabetes Complications study. AB - BACKGROUND: The formal identification of subgroups with varying levels of risk is uncommon in observational studies of cardiovascular disease, although such insight might be useful for clinical management. METHODS: Tree-structured survival analysis was utilized to determine whether there are meaningful subgroups at varying levels of cardiovascular disease risk in the Pittsburgh Epidemiology of Diabetes Complications study, a prospective cohort study of childhood-onset (<17 years old) type 1 diabetes. RESULTS: Of the 561 participants free of cardiovascular disease (coronary artery disease, stroke or lower extremity arterial disease) at baseline, 263 (46.9%) had an incident cardiovascular disease event over the 25-year follow-up. Tree-structured survival analysis revealed a range of risk groups, from 24% to 85%, which demonstrate that those with short diabetes duration and elevated non-high-density lipoprotein cholesterol have similar cardiovascular disease risk to those with long diabetes duration and that renal disease is a better discriminator of risk in men than in women. CONCLUSION: Our findings suggest that subgroups with major cardiovascular disease risk differences exist in this type 1 diabetes cohort. Using tree structured survival analysis may help to identify these groups and the interrelationships between their associated risk factors. This approach may improve our understanding of various clinical pathways to cardiovascular disease and help target intervention strategies. PMID- 27190083 TI - Ranirestat has a stronger inhibitory activity on aldose reductase and suppresses inflammatory reactions in high glucose-exposed endothelial cells. AB - OBJECTIVE: Under diabetic conditions, glucose is converted to sorbitol via aldose reductase, whose process could contribute to diabetic vascular complications. However, effects of aldose reductase inhibitors are modest in diabetic patients. This may be attributed to weak inhibitory activity of aldose reductase inhibitors. We compared effects of ranirestat on endothelial cell damage with those of epalrestat. MATERIALS AND METHODS: Intracellular formations of sorbitol and superoxide were measured by liquid chromatography-mass spectrometry-mass spectrometry and dihydroethidium staining, respectively. Vascular cell adhesion molecule-1 gene expression was analysed by reverse transcription polymerase chain reaction. THP-1 cell adhesion to human umbilical vein endothelial cells was evaluated using a fluorescent probe. RESULTS: High glucose significantly increased sorbitol levels, superoxide generation and vascular cell adhesion molecule-1 mRNA levels in, and THP-1 cell adhesion to, human umbilical vein endothelial cells, all of which were prevented by 500 nM ranirestat, but not epalrestat except for superoxide production. CONCLUSION: Our present results suggest that ranirestat has a stronger inhibitory activity on aldose reductase than epalrestat and suppresses inflammatory reactions in high glucose-exposed human umbilical vein endothelial cells. PMID- 27190084 TI - A preliminary study of brain macrovascular reactivity in impaired glucose tolerance and type-2 diabetes: Quantitative internal carotid artery blood flow using magnetic resonance phase contrast angiography. AB - OBJECTIVE: The aims of this study were (1) to examine cerebrovascular autoregulation in subjects with impaired glucose tolerance and type 2 diabetes and (2) to clarify whether cardiovascular autonomic nerve function is associated with abnormal cerebrovascular autoregulation. RESEARCH DESIGN AND METHODS: Totally, 46 subjects were recruited (12 = impaired glucose tolerance, 17 = type 2 diabetes and 17 = healthy volunteers). Arterial blood flow was assessed within the internal carotid artery at baseline and 20 min after intravenous pharmacological stress (1 g acetazolamide), using quantitative magnetic resonance phase-contrast angiography. Internal carotid artery vascular reactivity and pulsatility index was determined. All subjects underwent baroreceptor reflex sensitivity assessment. RESULTS: Subjects with impaired glucose tolerance and type 2 diabetes had significantly lower internal carotid artery vascular reactivity [40.2%(19.8) and 41.5%(18.7)], respectively, compared with healthy volunteers [57.0%(14.2); analysis of variance, p = 0.02]. There was no significant difference in internal carotid artery vascular reactivity between type 2 diabetes and impaired glucose tolerance groups (p = 0.84). There was a significant positive correlation between baroreceptor reflex sensitivity (low frequency:high frequency) with cardiac rhythm variability (rho = 0.47, p = 0.04) and PI (rho = 0.46, p = 0.04). CONCLUSION: We have demonstrated significant cerebrovascular haemodynamic abnormalities in subjects with type 2 diabetes and impaired glucose tolerance. This was associated with greater sympathovagal imbalance. This may provide an important mechanistic explanation for increased risk of cerebrovascular disease in diabetes. It also highlights that these abnormalities may already be present in prediabetes. PMID- 27190085 TI - The haptoglobin 2-2 genotype is associated with inflammation and carotid artery intima-media thickness. AB - The haptoglobin 2-2 genotype is associated with atherosclerosis in type 2 diabetes mellitus. We examined the associations of the haptoglobin 2-2 genotype with C-reactive protein (high-sensitivity C-reactive protein) and carotid artery intima-media thickness, adjusting for age, gender, ethnicity, type 2 diabetes mellitus, smoking status, body mass index, blood pressure, glycated haemoglobin, non-high-density lipoprotein cholesterol and medications via logistic multivariate regression in 200 subjects (160 type 2 diabetes mellitus versus 40 healthy individuals). The prevalence of the haptoglobin 2-2 genotype was 58% (115/200), higher in the Indians than in Chinese (72% versus 45%, p = 0.001). Multivariate analysis showed that the haptoglobin 2-2 genotype was associated with high-sensitivity C-reactive protein [mean: 3.5 +/- 3.9 versus 2.2 +/- 2.6 mg/L (non-haptoglobin 2-2), p < 0.001], haptoglobin concentration [mean: 116.9 +/ 54.4.0 versus 147.2 +/- 54.5 mg/dL (non-haptoglobin 2-2), p < 0.001] and average carotid artery intima-media thickness (multiplied by 10) [6.15 +/- 1.22 versus 5.98 +/- 1.20 mm (non-haptoglobin 2-2), p = 0.013]. This pilot study shows an association of the haptoglobin 2-2 genotype with low-grade inflammation, haptoglobin concentration and carotid artery intima-media thickness in multi ethnic Singapore. PMID- 27190086 TI - Amino acid metabolism reflecting arginase activity is increased in patients with type 2 diabetes and associated with endothelial dysfunction. AB - BACKGROUND: Endothelial dysfunction contributes to the development of vascular complication in diabetes. Arginase has emerged as a key mechanism behind endothelial dysfunction by its reciprocal regulation of nitric oxide production by substrate competition. We hypothesized that increased arginase activity in patients with type 2 diabetes shifts the metabolism of l-arginine from nitric oxide synthase to arginase resulting in an increase in the plasma ratio of ornithine/citrulline, and that this ratio is associated with endothelial dysfunction. METHODS: Forearm endothelium-dependent vasodilatation and endothelium-independent vasodilatation were determined in 15 patients with type 2 diabetes and 10 healthy controls and related to amino acids reflecting arginase and nitric oxide synthase activity. RESULTS: Compared to healthy controls, patients with diabetes had impaired endothelium-dependent vasodilatation and endothelium-independent vasodilatation. The ratios of ornithine/citrulline and proline/citrulline were 60% and 95% higher, respectively, in patients with diabetes than in controls (p < 0.001). The plasma ornithine/arginine ratio was 36% higher in patients with diabetes, indicating increased arginase activity. These ratios were inversely correlated to endothelium-dependent vasodilatation and endothelium-independent vasodilatation. CONCLUSION: Patients with diabetes and macrovascular complications have increased amino acid ratios reflecting a shift in arginine metabolism due to arginase activation. These changes are inversely related to endothelial function supporting that arginase activity contributes to endothelial dysfunction. PMID- 27190088 TI - Copeptin, insulin-like growth factor binding protein-1 and sitagliptin: A report from the BEta-cell function in Glucose abnormalities and Acute Myocardial Infarction study. AB - PURPOSE: To investigate whether sitagliptin affects copeptin and osmolality, suggesting arginine vasopressin activation and a potential for fluid retention, compared with placebo, in patients with a recent acute coronary syndrome and newly discovered type 2 diabetes or impaired glucose tolerance. A second aim was to confirm whether copeptin correlated with insulin-like growth factor binding protein-1. METHODS: Fasting blood samples were used from the BEta-cell function in Glucose abnormalities and Acute Myocardial Infarction trial, in which patients recently hospitalized due to acute coronary syndrome and with newly detected abnormal glucose tolerance were randomized to sitagliptin 100 mg once daily (n = 34) or placebo (n = 37). Copeptin, osmolality and insulin-like growth factor binding protein-1 were analysed at baseline and after 12 weeks. RESULTS: Copeptin and osmolality were unaffected by sitagliptin. There was no correlation between copeptin and insulin-like growth factor binding protein-1. CONCLUSION: Sitagliptin therapy does not appear to be related to activation of the arginine vasopressin system. PMID- 27190087 TI - Linagliptin and pioglitazone combination therapy versus monotherapy with linagliptin or pioglitazone: A randomised, double-blind, parallel-group, multinational clinical trial. AB - Linagliptin plus pioglitazone single-pill combinations were evaluated. Patients (n = 936) with insufficient glycaemic control, despite lifestyle interventions, were randomised for 30 weeks to either monotherapy with linagliptin 5 mg; pioglitazone 15, 30 or 45 mg; or single-pill combination with linagliptin 5 mg plus pioglitazone 15, 30 or 45 mg. An extension (?54 weeks) planned to evaluate linagliptin plus pioglitazone 30 or 45 mg single-pill combinations was not completed due to a protocol amendment. Adjusted mean (95% confidence interval) differences in HbA1c change from baseline at week 30 for linagliptin plus pioglitazone 15, 30 and 45 mg were -0.17% (-0.41, 0.07), -0.37% (-0.60, -0.14) and -0.41% (-0.64, -0.18) versus pioglitazone monotherapies, respectively, and 0.44% (-0.67, -0.20), -0.68% (-0.91, -0.44) and -0.89% (-1.12, -0.66) versus linagliptin monotherapy, respectively. Single-pill combinations were generally well tolerated. Hypoglycaemia frequency was ?1.5% per group. Linagliptin plus pioglitazone combinations were efficacious, with safety profiles comparable to the individual monotherapies. PMID- 27190089 TI - Role of Plasmodium vivax Duffy-binding protein 1 in invasion of Duffy-null Africans. AB - The ability of the malaria parasite Plasmodium vivax to invade erythrocytes is dependent on the expression of the Duffy blood group antigen on erythrocytes. Consequently, Africans who are null for the Duffy antigen are not susceptible to P. vivax infections. Recently, P. vivax infections in Duffy-null Africans have been documented, raising the possibility that P. vivax, a virulent pathogen in other parts of the world, may expand malarial disease in Africa. P. vivax binds the Duffy blood group antigen through its Duffy-binding protein 1 (DBP1). To determine if mutations in DBP1 resulted in the ability of P. vivax to bind Duffy null erythrocytes, we analyzed P. vivax parasites obtained from two Duffy-null individuals living in Ethiopia where Duffy-null and -positive Africans live side by-side. We determined that, although the DBP1s from these parasites contained unique sequences, they failed to bind Duffy-null erythrocytes, indicating that mutations in DBP1 did not account for the ability of P. vivax to infect Duffy null Africans. However, an unusual DNA expansion of DBP1 (three and eight copies) in the two Duffy-null P. vivax infections suggests that an expansion of DBP1 may have been selected to allow low-affinity binding to another receptor on Duffy null erythrocytes. Indeed, we show that Salvador (Sal) I P. vivax infects Squirrel monkeys independently of DBP1 binding to Squirrel monkey erythrocytes. We conclude that P. vivax Sal I and perhaps P. vivax in Duffy-null patients may have adapted to use new ligand-receptor pairs for invasion. PMID- 27190090 TI - Incoming human papillomavirus type 16 genome resides in a vesicular compartment throughout mitosis. AB - During the entry process, the human papillomavirus (HPV) capsid is trafficked to the trans-Golgi network (TGN), whereupon it enters the nucleus during mitosis. We previously demonstrated that the minor capsid protein L2 assumes a transmembranous conformation in the TGN. Here we provide evidence that the incoming viral genome dissociates from the TGN and associates with microtubules after the onset of mitosis. Deposition onto mitotic chromosomes is L2-mediated. Using differential staining of an incoming viral genome by small molecular dyes in selectively permeabilized cells, nuclease protection, and flotation assays, we found that HPV resides in a membrane-bound vesicle until mitosis is completed and the nuclear envelope has reformed. As a result, expression of the incoming viral genome is delayed. Taken together, these data provide evidence that HPV has evolved a unique strategy for delivering the viral genome to the nucleus of dividing cells. Furthermore, it is unlikely that nuclear vesicles are unique to HPV, and thus we may have uncovered a hitherto unrecognized cellular pathway that may be of interest for future cell biological studies. PMID- 27190091 TI - Optogenetic toolkit reveals the role of Ca2+ sparklets in coordinated cell migration. AB - Cell migration is controlled by various Ca(2+) signals. Local Ca(2+) signals, in particular, have been identified as versatile modulators of cell migration because of their spatiotemporal diversity. However, little is known about how local Ca(2+) signals coordinate between the front and rear regions in directionally migrating cells. Here, we elucidate the spatial role of local Ca(2+) signals in directed cell migration through combinatorial application of an optogenetic toolkit. An optically guided cell migration approach revealed the existence of Ca(2+) sparklets mediated by L-type voltage-dependent Ca(2+) channels in the rear part of migrating cells. Notably, we found that this locally concentrated Ca(2+) influx acts as an essential transducer in establishing a global front-to-rear increasing Ca(2+) gradient. This asymmetrical Ca(2+) gradient is crucial for maintaining front-rear morphological polarity by restricting spontaneous lamellipodia formation in the rear part of migrating cells. Collectively, our findings demonstrate a clear link between local Ca(2+) sparklets and front-rear coordination during directed cell migration. PMID- 27190092 TI - Leadership behaviours and healthcare research performance: prospective correlational study. AB - OBJECTIVES: The aims of the study were to determine whether differences in leadership self-perception/behaviour in healthcare researchers may influence research performance and to evaluate whether certain leadership characteristics are associated with enhanced leadership efficiency in terms of motivation, effectiveness and satisfaction. DESIGN AND PARTICIPANTS: All Faculty of Medicine Professors at Imperial College London (n=215) were sent the Multifactor Leadership Questionnaire (MLQ) Self form as a means of evaluating self-perception of leadership behaviours. MAIN OUTCOME MEASURES: For each professor, we extracted objective research performance measures (total number of publications, total number of citations and h index) from 1 January 2007 to 31 December 2009. The MLQ measured three leadership outcomes, which included motivation, effectiveness and satisfaction. Regression analysis was used to determine associations. RESULTS: A total number of 90 responses were received, which equated to a 42% response rate. There were no significant correlations between transformational, transactional or passive/avoidant leadership behaviours and any of the research performance measures. The five transformational leadership behaviours (ie, idealised attributes (IA), idealised behaviours (IB), inspirational motivation (IM), intellectual stimulation (IS), individual consideration (IC)) were highly significant predictors of leadership outcomes, extra effort (all B>0.404, SE=0.093-0.146, p<0.001), effectiveness (IA, IM, IS, IC B>0.359, SE=0.093-0.146, p<0.001; IB B=0.233, SE=0.103, p=0.026) and satisfaction (IA, IM, IS, IC B>0.483, SE=0.086-0.139, p<0.001; IB B=0.296, SE=0.101, p=0.004). Similarly, contingent reward was a significant predictor of extra effort (B=0.400, SE=0.123, p=0.002), effectiveness (B=0.353, SE=0.113, p=0.002) and satisfaction (B=0.326, SE=0.114, p=0.005). CONCLUSIONS: This study demonstrates that transformational leadership and contingent reward positively influence leadership efficiency in healthcare researchers. Although we did not show an association between leadership behaviours and research performance metrics, further studies using contextual performance measures at team and organisational levels are required. PMID- 27190093 TI - Outcomes of transfemoral transcatheter aortic valve implantation at hospitals with and without on-site cardiac surgery department: insights from the prospective German aortic valve replacement quality assurance registry (AQUA) in 17 919 patients. AB - AIMS: Performing transcatheter aortic valve implantation (TAVI) at hospitals with only cardiology department but no cardiac surgery (CS) on-site is at great odds with current Guidelines. METHODS AND RESULTS: We analysed data from the official, prospective German Quality Assurance Registry on Aortic Valve Replacement to compare characteristics and in-hospital outcomes of patients undergoing transfemoral TAVI at hospitals with (n = 75) and without CS departments (n = 22). An interdisciplinary Heart Team was established at all centres (internal staff physicians at hospitals with on-site CS; in-house cardiologists and visiting cardiac surgical teams from collaborating hospitals at non-CS hospitals). In 2013 and 2014, 17 919 patients (81.2 +/- 6.1 years, 55% females, German aortic valve (GAV) score 2.0 5.6 +/- 5.8%, logistic EuroSCORE I 21.1 +/- 15.4%) underwent transfemoral TAVI in Germany: 1332 (7.4%) at hospitals without on-site CS department. Patients in non-CS hospitals were older (82.1 +/- 5.8 vs. 81.1 +/- 6.1 years, P < 0.001), with more frequent co-morbidities. Predicted mortality risks per GAV-score 2.0 (6.1 + 5.5 vs. 5.5 +/- 5.9%, P < 0.001) and logEuroSCORE I (23.2 +/- 15.8 vs. 21.0 +/- 15.4%, P < 0.001) were higher in patients at non-CS sites. Complications, including strokes (2.6 vs. 2.3%, P = 0.452) and in-hospital mortality (3.8 vs. 4.2%, P = 0.396), were similar in both groups. Matched-pair analysis of 555 patients in each group with identical GAV-score confirmed similar rates of intraprocedural complications (9.2 vs. 10.3%, P = 0.543), strokes (3.2% for both groups, P = 1.00), and in-hospital mortality (1.8 vs. 2.9%, P = 0.234). CONCLUSION: Although patients undergoing TAVI at hospitals without on-site CS department were older and at higher predicted perioperative death risk, major complications, and in-hospital mortality were not statistically different, suggesting the feasibility and safety of Heart Team-based TAVI at non-CS sites. These findings need confirmation in future randomized study. PMID- 27190096 TI - Does knee replacement surgery for osteoarthritis improve survival? The jury is still out. AB - BACKGROUND: The relation of knee replacement (KR) surgery to all-cause mortality has not been well established owing to potential biases in previous studies. Thus, we aimed to examine the relation of KR to mortality risk among patients with knee osteoarthritis (OA) focusing on identifying biases that may threaten the validity of prior studies. METHODS: We included knee OA subjects (ages 50-89 years) from The Health Improvement Network, an electronic medical records database in the UK. Risk of mortality among KR subjects was compared with propensity score-matched non-KR subjects. To explore residual confounding bias, subgroup analyses stratified by age and propensity scores were performed. RESULTS: Subjects with KR had 28% lower risk of mortality than non-KR subjects (HR 0.72, 95% CI 0.66 to 0.78). However, when stratified by age, protective effect was noted only in older age groups (>63 years) but not in younger subjects (<=63 years). Further, the mortality rate among KR subjects decreased as candidacy (propensity score) for KR increased among subjects with KR, but no such consistent trend was noted among non-KR subjects. CONCLUSIONS: While a protective effect of KR on mortality cannot be ruled out, findings of lower mortality among older KR subjects and those with higher propensity scores suggest that prognosis based selection for KR may lead to intractable confounding by indication; hence, the protective effect of KR on all-cause mortality may be overestimated. PMID- 27190097 TI - Confirmation on the immunogenicity assay used in the SB4 phase III study: response to the comments by Meacci et al. PMID- 27190094 TI - Sustained safety and performance of the second-generation drug-eluting absorbable metal scaffold in patients with de novo coronary lesions: 12-month clinical results and angiographic findings of the BIOSOLVE-II first-in-man trial. AB - AIMS: Metal absorbable scaffolds constitute a conceptually attractive alternative to polymeric scaffolds. Promising 6-month outcomes of a second-generation drug eluting absorbable metal scaffold (DREAMS 2G), consisting of an absorbable magnesium scaffold backbone, have been reported. We assessed the 12-month safety and performance of this novel device. METHODS AND RESULTS: The prospective, international, multi-centre, first-in-man BIOSOLVE-II trial enrolled 123 patients with up to two de novo lesions with a reference diameter between 2.2 and 3.7 mm. All patients were scheduled for angiographic follow-up at 6 months, and-if subjects consented-at 12 months. Dual antiplatelet therapy was recommended for 6 months. Quantitative coronary angiography (QCA) parameters remained stable from 6 to 12 months [paired data of 42 patients: in-segment late lumen loss 0.20 +/- 0.21 mm vs. 0.25 +/- 0.22 mm, P = 0.117, Delta 0.05 +/- 0.21 mm (95% CI: 0.01;0.12); in-scaffold late lumen loss 0.37 +/- 0.25 mm vs. 0.39 +/- 0.27 mm, P = 0.446, Delta 0.03 +/- 0.22 (95% CI: -0.04;0.10), respectively]. Intravascular ultrasound and optical coherence tomography findings corroborated the QCA results. Target lesion failure occurred in four patients (3.4%), consisting of one death of unknown cause, one target-vessel myocardial infarction, and two clinically driven target lesion revascularization. No additional event occurred beyond the 6-month follow-up. During the entire follow-up of 12 months, none of the patients experienced a definite or probable scaffold thrombosis. CONCLUSION: The novel drug-eluting metal absorbable scaffold DREAMS 2G showed a continuous favourable safety profile up to 12 months and stable angiographic parameters between 6 and 12 months. CLINICALTRIALSGOV IDENTIFIER: NCT01960504. PMID- 27190095 TI - Biolimus-A9 polymer-free coated stent in high bleeding risk patients with acute coronary syndrome: a Leaders Free ACS sub-study. AB - Aims: Although a true clinical challenge, high bleeding risk patients with an acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) have never been specifically studied. Leaders Free ACS, a pre-specified Leaders Free sub-study, determined efficacy, and safety of a combination of 1-month dual anti-platelet therapy (DAPT) with implantation of either a polymer-free Biolimus A9-coated stent (BA9-DCS) or a bare-metal stent (BMS) in these patients. Methods and results: Leaders Free included 2466 patients undergoing PCI who had at least 1 of 13 pre-defined factors for an increased bleeding risk. Of these, 659 ACS patients were included in this analysis (BA9-DCS 330, BMS 329). At 12-month follow-up, treatment with the BA9-DCS was more effective (clinically driven target-lesion revascularization 3.9 vs. 9.0%, P = 0.009) and safer (cumulative incidence of cardiac death, myocardial infarction, or definite or probable stent thrombosis 9.3 vs. 18.5%, P = 0.001), driven by significantly lower rates of cardiac mortality (3.4 vs. 6.9%, P = 0.049) and myocardial infarction (6.9 vs. 13.8%, P = 0.005). Conclusion: We believe that the results of this sub-analysis from the Leaders Free trial are likely to significantly impact clinical practice for high bleeding risk patients presenting with an ACS: the use of a BMS can, in our view, no longer be recommended, and, given the paucity of available data for second-generation DES with shortened DAPT in these patients, the BA9-DCS should currently be considered as the device with the strongest evidence to support its use for this indication. PMID- 27190098 TI - Economic considerations and patients' preferences affect treatment selection for patients with rheumatoid arthritis: a discrete choice experiment among European rheumatologists. AB - OBJECTIVE: To compare the value that rheumatologists across Europe attach to patients' preferences and economic aspects when choosing treatments for patients with rheumatoid arthritis. METHODS: In a discrete choice experiment, European rheumatologists chose between two hypothetical drug treatments for a patient with moderate disease activity. Treatments differed in five attributes: efficacy (improvement and achieved state on disease activity), safety (probability of serious adverse events), patient's preference (level of agreement), medication costs and cost-effectiveness (incremental cost-effectiveness ratio (ICER)). A Bayesian efficient design defined 14 choice sets, and a random parameter logit model was used to estimate relative preferences for rheumatologists across countries. Cluster analyses and latent class models were applied to understand preference patterns across countries and among individual rheumatologists. RESULTS: Responses of 559 rheumatologists from 12 European countries were included in the analysis (49% females, mean age 48 years). In all countries, efficacy dominated treatment decisions followed by economic considerations and patients' preferences. Across countries, rheumatologists avoided selecting a treatment that patients disliked. Latent class models revealed four respondent profiles: one traded off all attributes except safety, and the remaining three classes disregarded ICER. Among individual rheumatologists, 57% disregarded ICER and these were more likely from Italy, Romania, Portugal or France, whereas 43% disregarded uncommon/rare side effects and were more likely from Belgium, Germany, Hungary, the Netherlands, Norway, Spain, Sweden or UK. CONCLUSIONS: Overall, European rheumatologists are willing to trade between treatment efficacy, patients' treatment preferences and economic considerations. However, the degree of trade-off differs between countries and among individuals. PMID- 27190100 TI - Evaluation of delayed puberty: what diagnostic tests should be performed in the seemingly otherwise well adolescent? AB - Delayed puberty (DP) is defined as the lack of pubertal development by an age that is 2-2.5 SDs beyond the population mean. Although it generally represents a normal variant in pubertal timing, concern that DP could be the initial presentation of a serious underlying disorder has led to a diagnostic approach that is variable and may include tests that are unnecessary and costly. In this review, we examine available literature regarding the recommended diagnostic tests and aetiologies identified during the evaluation of youth with DP. We view this literature through the prism of the seemingly otherwise well adolescent. To provide further clinical context, we also evaluate the clinical and laboratory data from patients seen with DP in our centre over a 2-year period. The literature and our data reveal wide variability in the number of tests performed and raise the question of whether tests, other than gonadotropins, obtained in the absence of signs or symptoms of an underlying disorder are routinely warranted. Together this information provides a pragmatic rationale for revisiting recommendations calling for broad testing during the initial diagnostic evaluation of an otherwise healthy adolescent with DP. We highlight the need for further research comparing the utility of broader screening with a more streamlined approach, such as limiting initial testing to gonadotropins and a bone age, which, while not diagnostic, is often useful for height prediction, followed by close clinical monitoring. If future research supports a more streamlined approach to DP, then much unnecessary testing could be eliminated. PMID- 27190101 TI - Early clinical and echocardiographic outcomes after SAPIEN 3 transcatheter aortic valve replacement in inoperable, high-risk and intermediate-risk patients with aortic stenosis. AB - AIMS: Based on randomized trials using first-generation devices, transcatheter aortic valve replacement (TAVR) is well established in the treatment of high-risk (HR) patients with severe aortic stenosis (AS). To date, there is a paucity of adjudicated, prospective data evaluating outcomes with newer generation devices and in lower risk patients. We report early outcomes of a large, multicentre registry of inoperable, HR, and intermediate-risk (IR) patients undergoing treatment with the next-generation SAPIEN 3 transcatheter heart valve (THV). METHODS AND RESULTS: Patients with severe, symptomatic AS (583 high surgical risk or inoperable and 1078 IR) were enrolled in a multicentre, non-randomized registry at 57 sites in the USA and Canada. All patients received TAVR with the SAPIEN 3 system via transfemoral (n = 1443, 86.9%) and transapical or transaortic (n = 218, 13.1%) access routes. The rate of 30-day all-cause mortality was 2.2% in HR/inoperable patients [mean Society of Thoracic Surgeons (STS) score 8.7%] and 1.1% in IR patients (mean STS score 5.3%); cardiovascular mortality was 1.4 and 0.9%, respectively. In HR/inoperable patients, the 30-day rate of major/disabling stroke was 0.9%, major bleeding 14.0%, major vascular complications 5.1%, and requirement for permanent pacemaker 13.3%. In IR patients, the 30-day rate of major/disabling stroke was 1.0%, major bleeding 10.6%, major vascular complications 6.1%, and requirement for permanent pacemaker 10.1%. Mean overall Kansas City Cardiomyopathy Questionnaire score increased from 47.8 to 67.8 (HR/inoperable, P < 0.0001) and 54.7 to 74.0 (IR, P < 0.0001). Overall, paravalvular regurgitation at 30 days was none/trace in 55.9% of patients, mild in 40.7%, moderate in 3.4%, and severe in 0.0%. Mean gradients among patients with paired baseline and 30-day or discharge echocardiograms decreased from 45.8 mmHg at baseline to 11.4 mmHg at 30 days, while aortic valve area increased from 0.69 to 1.67 cm(2). CONCLUSIONS: The SAPIEN 3 THV system was associated with low rates of 30-day mortality and major/disabling stroke as well as low rates of moderate or severe paravalvular regurgitation. TRIAL REGISTRATION: ClinicalTrials.gov #NCT01314313. PMID- 27190102 TI - Electrocardiographic screening of children and adolescents: the search for hidden risk. PMID- 27190099 TI - Omega-3 fatty acids are associated with a lower prevalence of autoantibodies in shared epitope-positive subjects at risk for rheumatoid arthritis. AB - OBJECTIVES: Previously, we found that omega-3 fatty acids (n-3 FAs) were inversely associated with anti-cyclic citrullinated peptide (anti-CCP) positivity in participants at risk for future rheumatoid arthritis (RA). We investigated whether n-3 FAs were also associated with rheumatoid factor (RF) positivity and whether these associations were modified by shared epitope (SE) positivity. METHODS: The Studies of the Etiology of RA (SERA) cohort includes RA-free participants who are at increased risk for RA. We conducted a nested case-control study (n=136) to determine the association between RF and anti-CCP2 positivity and n-3 FA percentage in erythrocyte membranes (n-3 FA% in red blood cells (RBCs)). Additionally, in the baseline visit of the SERA cohort (n=2166), we evaluated the association between reported n-3 FA supplement use and prevalence of RF and anti-CCP2. We assessed SE positivity as an effect modifier. RESULTS: In the case-control study, increasing n-3 FA% in RBCs was inversely associated with RF positivity in SE-positive participants (OR 0.27, 95% CI 0.10 to 0.79), but not SE-negative participants. Similar associations were seen with anti-CCP positivity in SE-positive participants (OR 0.42, 95% CI 0.20 to 0.89), but not SE-negative participants. In the SERA cohort at baseline, n-3 FA supplement use was associated with a lower prevalence of RF positivity in SE-positive participants (OR 0.32, 95% CI 0.12 to 0.82), but not SE-negative participants; similar but non significant trends were observed with anti-CCP2. CONCLUSIONS: The potential protective effect of n-3 FAs on RA-related autoimmunity may be most pronounced in those who exhibit HLA class II genetic susceptibility to RA. PMID- 27190104 TI - Switching from clopidogrel to prasugrel or ticagrelor: tips and tricks. PMID- 27190103 TI - Low-gradient aortic stenosis. AB - An important proportion of patients with aortic stenosis (AS) have a 'low gradient' AS, i.e. a small aortic valve area (AVA <1.0 cm(2)) consistent with severe AS but a low mean transvalvular gradient (<40 mmHg) consistent with non severe AS. The management of this subset of patients is particularly challenging because the AVA-gradient discrepancy raises uncertainty about the actual stenosis severity and thus about the indication for aortic valve replacement (AVR) if the patient has symptoms and/or left ventricular (LV) systolic dysfunction. The most frequent cause of low-gradient (LG) AS is the presence of a low LV outflow state, which may occur with reduced left ventricular ejection fraction (LVEF), i.e. classical low-flow, low-gradient (LF-LG), or preserved LVEF, i.e. paradoxical LF LG. Furthermore, a substantial proportion of patients with AS may have a normal flow, low-gradient (NF-LG) AS: i.e. a small AVA-low-gradient combination but with a normal flow. One of the most important clinical challenges in these three categories of patients with LG AS (classical LF-LG, paradoxical LF-LG, and NF-LG) is to differentiate a true-severe AS that generally benefits from AVR vs. a pseudo-severe AS that should be managed conservatively. A low-dose dobutamine stress echocardiography may be used for this purpose in patients with classical LF-LG AS, whereas aortic valve calcium scoring by multi-detector computed tomography is the preferred modality in those with paradoxical LF-LG or NF-LG AS. Although patients with LF-LG severe AS have worse outcomes than those with high gradient AS following AVR, they nonetheless display an important survival benefit with this intervention. Some studies suggest that transcatheter AVR may be superior to surgical AVR in patients with LF-LG AS. PMID- 27190105 TI - Drosophila Pkaap regulates Rab4/Rab11-dependent traffic and Rab11 exocytosis of innate immune cargo. AB - The secretion of immune-mediators is a critical step in the host innate immune response to pathogen invasion, and Rab GTPases have an important role in the regulation of this process. Rab4/Rab11 recycling endosomes are involved in the sorting of immune-mediators into specialist Rab11 vesicles that can traffic this cargo to the plasma membrane; however, how this sequential delivery process is regulated has yet to be fully defined. Here, we report that Drosophila Pkaap, an orthologue of the human dual-specific A-kinase-anchoring protein 2 or D-AKAP2 (also called AKAP10), appeared to have a nucleotide-dependent localisation to Rab4 and Rab11 endosomes. RNAi silencing of pkaap altered Rab4/Rab11 recycling endosome morphology, suggesting that Pkaap functions in cargo sorting and delivery in the secretory pathway. The depletion of pkaap also had a direct effect on Rab11 vesicle exocytosis and the secretion of the antimicrobial peptide Drosomycin at the plasma membrane. We propose that Pkaap has a dual role in antimicrobial peptide traffic and exocytosis, making it an essential component for the secretion of inflammatory mediators and the defence of the host against pathogens. PMID- 27190107 TI - Impact of white striping on functionality attributes of broiler breast meat1. AB - The influence of white striping (WS) on the water-holding capacity (WHC) and protein functionality attributes of broiler breast meat was investigated. Boneless breast fillets (Pectoralis major) were collected from the deboning line of a commercial processing plant and categorized by WS score (normal, moderate, severe). The physical (weight, pH, CIE-color values), water-holding capacity (salt-induced water uptake, cook loss, final yield), protein functionality (solubility, emulsifying activity), and protein composition (SDS-PAGE) characteristics of the fillets were measured in three experiments. Breast meat with WS exhibited greater fillet weights, higher pH, and similar color values (L*a*b*) to normal fillets. In experiment 1, fillets were frozen-thawed prior to analysis. The WS condition reduced thaw loss, sarcoplasmic protein solubility, and the emulsifying activity of the myofibrillar proteins, but did not significantly affect salt-induced water uptake, cook loss, final yield, or myofibrillar protein solubility. In experiment 2, breast meat was analyzed fresh and after a freeze-thaw cycle. Freezing samples prior to analysis negatively influenced WHC and reduced sarcoplasmic protein solubility in both WS and normal fillets. In fresh and frozen-thawed meat, the WS condition decreased sarcoplasmic protein solubility but did not significantly alter WHC or myofibrillar protein solubility. For experiment 3, fillets were portioned into 3 sections (Location A, cranial end-ventral surface; Location B, cranial end-dorsal surface; Location C, caudal end). The effects of WS on WHC and protein solubility were dependent upon breast fillet sampling location. Fillets with WS exhibited lower salt-induced water uptake, greater cook loss, and lower sarcoplasmic protein solubility than normal fillets when sampled from location A. SDS-PAGE analysis indicated that differences in the composition of sarcoplasmic and myofibrillar protein fractions between WS and normal fillets were influenced by sampling location. These results suggest that WS diminishes the WHC and protein functionality of broiler breast meat, but demonstrate that the WS effects on these traits are not uniform throughout the breast muscle. PMID- 27190106 TI - Metal ion-oxytetracycline pharmacokinetic interactions after oral co administration in broiler chickens. AB - The influence of the composition of calcium (Ca(2+)), magnesium (Mg(2+)), and iron (Fe(3+)) ions in two concentration levels (low-500 mg/L of CaCl2, 125 mg/L of MgCl2, and 10 mg/L of FeCl3 and high-2,500 mg/L of CaCl2, 625 mg/L of MgCl2, and 50 mg/L of FeCl3) contained in water on the pharmacokinetics (PK) of oxytetracycline (OTC) was determined. OTC hydrochloride was administered at a dose of 25 mg/kg of body weight to broiler chickens divided into four groups of nine birds each, including 3 oral groups (in deionized water -control, in water with low ion concentration, and in water with high ion concentration) and 1 intravenous group. OTC concentrations in plasma were determined using liquid chromatography-tandem mass spectrometry, after which non-compartmental pharmacokinetic analysis was conducted.The absolute bioavailability of OTC in the group of birds exposed to higher ions concentration was reduced (8.68% +/- 2.56) as compared to the control (13.71% +/- 2.60). Additionally, in this group, decrease in PK parameters such as: area under the concentration-time curve from 0 to infinity (15.36 MUg * h/mL +/- 4.36), from 0 to t (14.78 MUg * h/mL +/- 4.37), area under the first moment of curve from 0 to t (107.54 MUg * h/mL +/- 36.48), and maximum plasma concentration (2.13 MUg/mL +/- 0.32) were also observed. It is noteworthy, all mentioned parameters demonstrated a downward trend with high correlation coefficient (P = 0.004, P = 0.002, P = 0.005, P = 0.004, P = 0.011, respectively), reflecting the influence of increasing concentrations of Ca(2+), Mg(2+), and Fe(3+) ions on the decreasing absorption rate of OTC.Based on the current research results, it can be assumed that high concentrations of several ions applied concomitantly are able to decrease the absorption of OTC from gastrointestinal tract in broiler chickens. This occurrence might impair the drug's clinical efficacy toward some pathogenic microorganisms. It implies that using OTC on a farm may require administration of higher doses than the routine one when infections are caused by less sensitive pathogens. PMID- 27190108 TI - Genetic parameters of egg quality traits in long-term pedigree recorded Japanese quail. AB - This study was conducted to determine the genetic parameters of internal and external quality traits of Japanese quail eggs. Two statistical models were used in the calculation of genetic parameters and variance components. While 286 eggs were used based on model 1, 1,524 eggs were used based on model 2. Genetic parameters of the first eggs were calculated with direct genetic effect included in the analysis as random factors by using model 1. Model 2 was used for all eggs (5 to 6 eggs from each hen for six rearing groups). As different from model 1, their permanent environmental effects were also included in the model 2. Heritability of egg weight, egg length, egg width, shape index, shell weight, shell thickness, and shell ratio among the external quality traits of the eggs was respectively found to be 0.44, 0.53, 0.51, 0.70, 0.19, 0.16, and 0.05, respectively, according to model 1. These values were found to be 0.46, 0.40, 0.74, 0.48, 0.60, 0.28, and 0.21, respectively, according to model 2. Yolk weight, yolk diameter, yolk height, yolk index, yolk ratio, albumen weight, albumen height, albumen ratio, and Haugh unit values among the internal quality traits of the egg were found to be 0.22, 0.32, 0.02, 0.16, 0.19, 0.34, 0.19, 0.17, and 0.17, respectively, according to model 1. These internal quality traits were found to be 0.27, 0.18, 0.38, 0.06, 0.20, 0.41, 0.15, 0.15, and 0.12, respectively, according to model 2. Consequently, in this study, strong genetic correlations were detected between albumen height and Haugh unit, and also between albumen height and albumen weight. Additionally, a high and positive correlation was observed between some yolk traits (yolk weight and diameter) and albumen traits (weight and height). All these genetic correlations can be used to improve egg quality with a selection according to albumen weight. PMID- 27190109 TI - Relationship between different enteric viral infections and the occurrence of diarrhea in broiler flocks in Jordan. AB - The aim of this study is to determine if enteric viruses are the cause of diarrhea in broiler flocks in Jordan. Intestinal content samples were collected from 101 broiler flocks from several regions of Jordan to detect the presence of astrovirus, coronavirus, reovirus, and rotavirus, by using reverse transcriptase polymerase chain reaction (RT-PCR). Forty-six of these flocks were clinically healthy with no enteric disease, and the other 55 flocks were clinically suffering from diarrhea. The samples were collected between 5 and 16 d of age. The results show that 79% of total 101 flocks tested were infected with one or more of the above enteric viruses. Coronavirus was the most common virus, detected in 56.4% of these flocks, with astrovirus in 29.7% of the flocks, and rotavirus (9.9%) and reovirus (5.6%) being the least common. None of these flocks were found to be infected with all four viruses, but one of the flocks was found to be infected with astrovirus, coronavirus, and rotavirus simultaneously. Individual infection was noted with astrovirus, coronavirus and rotavirus but not with reovirus, whereas all flocks infected with reovirus were also infected with coronavirus. There was no statistical evidence to link these viruses as the main cause of diarrhea in the flocks tested. This is the first study in Jordan to detect all of these viruses and to correlate their presence with diarrhea in chicken flocks. PMID- 27190110 TI - Determination of the adequate dose of garlic diallyl disulfide and diallyl trisulfide for effecting changes in growth performance, total-tract nutrient and energy digestibility, ileal characteristics, and serum immune parameters in broiler chickens. AB - The objective of the current experiment was to determine the adequate dose and impact of graded concentrations of garlic diallyl disulfide (DADS) and diallyl trisulfide (DATS) on growth performance, total-tract nutrient and energy digestibility, serum immune parameters, and ileal morphology in broiler chickens. At 28-d post-hatch, male broiler chickens were allotted on the basis of initial body weight (1.34 +/- 0.106 kg) in a randomized complete block desing ( RCBD: ) to one of six treatments that consisted of an oral gavage of 0, 0.45, 0.90, 1.80, 3.6, or 7.2 mg of DADS + DATS per kg bodyweight (BW) with 8 replicate cages per treatment and 4 birds per cage. The DADS + DATS was administered to birds by daily oral gavage for a period of 6 d. Growth performance was recorded and excreta were collected for analysis of DM, nitrogen ( N: ), and energy ( E: ) digestibility and on the last day of the experiment, the median bird in each cage was euthanized and the mid ileum was excised for morphological and gene expression measurements and blood was collected for serum natural antibody and complement assays. Body weight gain and villus height were linearly increased (P < 0.01) with oral gavage of DADS + DATS. There was a quadratic effect (P < 0.01) of the oral gavage on digestibility of DM, N, and E that corresponded to an average broken-line regression-derived adequate dose of 1.16 mg DADS + DATS per kg BW. Supplementation of DADS + DATS by oral gavage had no impact on gene expression markers although there was a tendency for an increase (P = 0.10) in serum natural antibody activity due to treatment. Results from the current study indicate that supplementation of a gavage containing DADS + DATS improves BW gain, ileal morphology, and digestibility of DM, N, and E and may affect serum immune parameters in broiler chickens. The average broken-line regression-derived adequate dose to optimize BW gain and villus height response was 2.51 mg DADS + DATS per kg BW. PMID- 27190111 TI - Interactive effects of dietary adaptation period length and titration diet type on apparent ileal phosphorus digestibility and phosphorus retention in growing broilers. AB - Two experiments were conducted to examine the effects of different corn titration diets and dietary adaptation period length (DAPL) on intestinal histology, apparent ileal P digestibility (AIPD), and apparent P retention (APR) in Ross * Ross 708 male broilers from 20 to 24 d of age. It was hypothesized that purified ingredients in nutrient-deficient titration diets may affect P availability with varying DAPL. In experiment 1, 1,152 broilers were utilized in a 3 * 3 factorial treatment structure with 3 diets (control, 25% corn titration diet [25CTD], or 75% corn titration diet [75CTD]) and 3 DAPL (0, 24, or 72 h). Experiment 2 was conducted with 576 broilers as a 4 * 3 factorial arrangement with 4 diets (control, 25CTD, 75CTD, or nitrogen-free diet [NFD]) and 3 DAPL (24, 48, or 72 h). All diets contained purified ingredients except for the control diet, which had the same formulation as the common starter and served as a control for DAPL. The NFD diet was fed as a highly purified protein-free diet. Broilers were fed a common diet until 19 d of age and then transferred to experimental diets at 20 d of age. In experiment 1, diet type did not affect (P > 0.05) intestinal histology. However, diet type and DAPL each influenced (P.<=.0.001) diet AIPD. Higher (P.<=.0.001) AIPD was measured for the control diet compared with the 75CDT, and the 25CTD had the lowest AIPD. Following a 24 h DAPL, AIPD was higher (P.<=.0.001) than after a DAPL of 0 or 72 h. In experiment 2, diet type * DAPL interactions (P.<=.0.001) were observed for APR of the control diet, 75CTD, and NFD, but not the 25CTD. Because APR of the control diet was affected by varying DAPL, factors other than differences in diet type may have been responsible for inconsistencies in the measure of P availability. Furthermore, no clear evidence was observed that broilers were able to adapt to P-deficient diets by increasing APR or AIPD. In conclusion, a standard DAPL should be established as a means to reduce variability associated with measuring of feedstuff P availability. PMID- 27190112 TI - Disseminated histiocytic sarcoma in a child: a clinicopathological dichotomy with 8 years survival. AB - A 3-year-old girl presented with a non-healing ulcer, originating as a pustule over the right anterior chest wall of 11/2 month duration associated with high fever. A subcutaneous nodule along with right apical and anterior axillary lymph nodes was palpable. Abdominal ultrasound and chest skiagram were normal. Fine needle aspiration cytology (FNAC) from the axillary lymph node was suggestive of embryonal rhabdomyosarcoma. Bone marrow aspirate was normal. The ulcer and subcutaneous nodule were excised completely with adequate margins. Histopathological examinations were compatible with malignancy of histiocytic origin with clear resected margins. The axillary nodes were free of tumour. Adjuvant chemotherapy was given for 13 months. The patient is doing well at 8 years follow-up. PMID- 27190113 TI - Conjunctival metastatic adenocarcinoma of unknown origin. AB - We describe the case of a presumed metastatic adenocarcinoma discovered in the conjunctival limbus of a 75-year-old male with a history of prostate adenocarcinoma. After an initial clinical diagnosis of pinguecula and unsuccessful topical steroid therapy, the lesion was excised and sent for pathological evaluation and special staining. The histopathological evaluation was consistent with a diagnosis of adenocarcinoma, without evidence of lacrimal tissue. Surprisingly, results from special staining were most consistent with lung adenocarcinoma rather than that from a prostate origin. Systemic radiographic evaluation did not locate the primary tumour, and the patient did not present with any symptoms consistent with malignancy. Watchful waiting was chosen as the therapeutic strategy to manage the patient. This is the first report of an adenocarcinoma, likely metastatic, at the conjunctival limbus. PMID- 27190114 TI - Hyperimmunoglobulinaemia D syndrome: a rare cause of prolonged fever and treatment with anti-interleukin 1 agent. AB - Hyperimmunoglobulinaemia D syndrome (HIDS) is an autosomal recessive, autoinflammatory disease that is characterised with intermittent febrile episodes, cervical lymphadenopathy, rashes, arthritis and gastrointestinal symptoms associated with synovial or serosal inflammation. HIDS is caused by mutations in the gene encoding mevalonate kinase enzyme. The febrile attacks usually start in early childhood and triggered by stress or vaccinations. We report a case of 16-month-old boy who had episodes of recurrent fever accompanied by maculopapular rash and lymphadenopathy. He was diagnosed as HIDS and he had heterozygote mutation of mevalonate kinase gene. PMID- 27190115 TI - Idiopathic spinal cord herniation of the cervical cord: unusual cause of proximal muscle weakness in upper limbs. AB - Idiopathic spinal cord herniation (ISCH) is a recognised rare cause of progressive and potentially curable myelopathy. Around 170 cases have been described in the literature, all to be found between the T2 and T8 vertebrae. We report a case of ISCH in the cervical region. A 23-year-old man with no history of trauma presented with a 6-year history of bilateral mild resting hand tremor and left scapular pain radiating to the left arm for a duration of 8 months. Nerve conduction studies showed some denervation changes of the upper limbs and bulbar regions. MRI of the spine showed anterior midline herniation of the spinal cord at the level of C7 vertebra with an associated collection of cerebrospinal fluid in the extradural space in the cervical region. Owing to the non progressive nature of symptoms, currently the patient is managed conservatively. PMID- 27190117 TI - Management of a case of caesarean scar pregnancy and all its complications. AB - Caesarean scar pregnancy is a rare form of an ectopic pregnancy that can lead to serious consequences like massive bleeding and uterine rupture. Although there is no consensus for treatment, many treatment options have been described. We present a female patient who had to undergo most of these available treatments due to unforeseen circumstances. These treatments include local injection of methotrexate and potassium chloride into the pregnancy, transcervical aspiration of the pregnancy under laparoscopic guidance, balloon occlusion of the internal iliac arteries and eventually a laparoscopic hysterectomy. She also developed a complication of vault dehiscence due to an abscess formation after her hysterectomy. Owing to the potential need for multiple interventions and admissions, adequate counselling is required for these patients to manage their expectations in what is usually a very difficult situation. PMID- 27190116 TI - Successful vaginal delivery following spontaneous adrenal haemorrhage at term. AB - Spontaneous adrenal haemorrhage (SAH) is a rare event in the general population, estimated to be around 0.3-1.8%. The exact incidence in pregnancy is unknown but rare. Most cases of SAH at or near term have presented with massive haemorrhage and haemodynamic instability, requiring emergency caesarean delivery or intrauterine fetal death. This is the first reported case of a successful vaginal delivery after acute, spontaneous, left adrenal haemorrhage at term. PMID- 27190118 TI - Pancreaticopericardial fistula: a rare complication of chronic pancreatitis. AB - Pancreaticopericardial fistula (PPF) is an extremely rare clinical problem encountered in patients with chronic pancreatitis. The diagnosis should be suspected if a patient presents with pericardial effusion on a background of chronic pancreatitis. Significantly raised amylase in the pericardial fluid offers an important clue for the diagnosis. CT is the initial imaging modality to look for pancreatic and pericardial changes. The therapeutic options include medical, endoscopic or surgical interventions. Medical and endoscopic therapies are the preferred modes of treatment while surgery is reserved for those who fail these measures. PMID- 27190119 TI - Carotid artery aneurysm: last among equals. AB - A 66-year-old man presented initially with a swelling in the left side of the neck, which was confirmed to be a carotid artery aneurysm on ultrasonography. He was subsequently admitted reporting intermittent episodes of visual loss in the left eye and right arm weakness. Further imaging confirmed multiple, small acute infarcts in the left cerebral hemisphere. The patient underwent open repair of the aneurysm and made an uncomplicated recovery with no persisting neurological deficit. PMID- 27190121 TI - In the thick of it: cerebral venous sinus thrombosis precipitated by iron deficiency anaemia and sickle cell trait. PMID- 27190120 TI - Thymic hyperplasia and its spontaneous resolution with treatment of Graves' hyperthyroidism. PMID- 27190122 TI - Pancreatic gout and the role of multimodality imaging in its management. AB - Uric acid deposition in the pancreas is very rare and neither an endoscopic ultrasound (EUS) nor a contrast-enhanced CT image of this condition has ever been published. We describe a case of asymptomatic pancreatic gout that was detected incidentally on CT. Imaging features mimicked pancreatic neoplasm, warranting further evaluation with EUS-guided fine-needle aspiration. Samples revealed debris encrusted with monosodium urate crystals. Follow-up CT showed complete resolution with urate-lowering therapy. We aim to augment current knowledge on the imaging of pancreatic gout and discuss its management. PMID- 27190124 TI - Positional hoarseness: an unusual symptom in jugular foramen mass. AB - We came across a case of jugular foramen mass causing positional hoarseness on turning the head left and disappearing on returning the head to a straight position. Hoarseness of voice due to vagus nerve involvement is seen in jugular foramen mass but positional hoarseness has never been seen before. We report this rarest presentation and discuss the pathophysiology behind it. PMID- 27190123 TI - Temporary leadless pacing in a patient with severe device infection. AB - A 64-year-old patient underwent implantation of a transcatheter pacing systems (TPS) for severe lead endocarditis. The patient experienced fever after a dental procedure. On the transoesophageal echocardiogram (TEE), vegetations were attached to the leads. Because the patient was pacemaker dependent, a temporary pacing lead had to be placed. After removal, however, he did not improve. A second TEE showed new vegetations. Ventricular fibrillation occurred spontaneously; so isoprenalin had to be stopped and a new lead was implanted. Vegetations appeared soon after the new temporary lead was placed. We used a TPS as a bridging device, followed by implantation of a resynchronisation system, and explantation of the TPS. After the Micra TPS was implanted, the patient recovered noticeably. All inflammation parameters were negative and an additional (18)F fluorodeoxyglucose-positron emission tomography/CT imaging also proved to be negative. So a CRT-D device was then implanted, and the TCP was removed. PMID- 27190125 TI - Partners for life. AB - The hormones insulin and glucagon both play important roles in the development of diabetes. PMID- 27190126 TI - Effectiveness and safety of dexamethasone implants for postsurgical macular oedema including Irvine-Gass syndrome: the EPISODIC-2 study. AB - AIM: To assess the effectiveness of intravitreal dexamethasone implants for treating postsurgical macular oedema (PSMO) including Irvine-Gass syndrome and determining the predictive factors of treatment response. METHODS: Descriptive, observational, retrospective, consecutive, uncontrolled, multicentre, national case series. One hundred patients were included between April 2011 and June 2014, with a minimum of 1-year follow-up. Patients received dexamethasone implant 0.7 mg at baseline. Clinical characteristics, best-corrected visual acuity (BCVA), central subfield macular thickness (CSMT) and intraocular pressure were measured at each visit. The main outcome measure was the change in BCVA (Early Treatment of Diabetic Retinopathy Study (ETDRS) letters: L). An analysis of predictive factors of treatment response is also provided. RESULTS: Mean improvement in BCVA was 9.6 (+/-10.6) L at month 6 and 10.3 (+/-10.7) L at month 12 (p<0.001). The proportion of eyes with gains in BCVA of 15 or more letters was 32.5% and 37.5% at months 6 and 12, respectively. The mean reduction in CSMT was 135.2 and 160.9 um at months 6 and 12, respectively (p<0.001). Thirty-seven per cent of patients did not need a second injection after the first injection during follow-up. The presence of at least one PSMO risk factor decreases the probability of a gain in visual acuity (VA) >=10 L (p=0.006). Initial VA <=50 L at baseline and non-naive status decrease the probability of having only one injection during follow-up (p=0.044). CONCLUSIONS: The significant gain in BCVA from baseline achieved at month 6 was maintained at month 12 after intravitreal injection of dexamethasone implant. Naive status seems to be a good predictive factor of treatment response. PMID- 27190127 TI - Three-month outcome of intravitreal ziv-aflibercept in eyes with diabetic macular oedema. AB - PURPOSE: We report the 3-month efficacy of monthly intravitreal ziv-aflibercept in patients with diabetic macular oedema (DME). METHODS: Prospectively, consecutive patients with DME underwent intravitreal injection of 0.05 ml of compounded ziv-aflibercept (1.25 mg) from March 2015 to November 2015. Monitoring of best-corrected visual acuity (BCVA), intraocular inflammation, cataract progression and retinal structure by spectral domain optical coherence tomography was carried out at baseline, 1 week, 1 month, 2 months and 3 months after 3 monthly injections. RESULTS: A total of 17 eyes (11 right eyes and 6 left eyes) were treated. The participants were divided into 10 Caucasians and 6 Indians, 11 men and 5 women, and had a mean age of 61.5 years. Five eyes were treatment-naive cases and 12 eyes were treatment non- naive with last treatment received at least more than 4-month interval. Mean BCVA in log MAR (equivalent Snellen visual acuity) improved from baseline 0.70 (20/100) to 0.49 (20/60) at 1 month, 0.43 (20/50) at 2 months and 0.42 (20/50) at 3 months (p <= 0.003). Central macular thickness decreased from mean baseline 517.5 to 388.1 MUm at 1 week, 355.4 MUm at 1 month, 351.4 MUm at 2 months and 322.2 MUm at 3 months (p <= 0.001). CONCLUSIONS: Off-label use of intravitreal ziv-aflibercept improves visual acuity, without detectable ocular toxicity or systemic side effects in DME. It offers a less expensive alternative to the approved intravitreal aflibercept (Eylea), especially in the low/middle-income countries and in countries where Eylea is not available. PMID- 27190129 TI - MicroRNA 486-3P as a stability marker in acute coronary syndrome. AB - Easily accessible biomarkers are needed to diagnose cardiovascular disease precisely-particularly, to distinguish between disease subtypes that are encountered in clinical practice. Per the hypothesis that plasma miRNA is valuable for this purpose, we performed complete transcriptional profiling of an miRNA discovery-set in 14 samples: three patients with ST-elevated acute myocardial infarction (STEMI) at baseline and after three months of follow-up, four with stable ischaemic heart disease (stable-IHD) and four healthy age matched volunteers. Our aim was to determine whether we could distinguish patients with unstable plaques from stable patients following a STEMI event. After analysing miRNA profiles, we conducted a validation study comparing three month STEMI (n=40) with stable-IHD (n=35), which confirmed that miR-486-3P differentiates patients with three-month STEMI from those with stable-IHD (P=0.019). PMID- 27190128 TI - Choroidal structure in eyes with drusen and reticular pseudodrusen determined by binarisation of optical coherence tomographic images. AB - PURPOSE: To compare luminal and stromal area of the choroid in eyes with drusen and reticular pseudodrusen (RPD) and to investigate their changes over 24 months. METHODS: In eyes with drusen and RPD and control subjects, total choroidal, luminal and stromal area were measured on optical coherence tomography B-scans converted to binary images, at baseline and after 24 months. RESULTS: Eighteen eyes of 18 subjects for each group were included. In drusen and RPD, we found reduction of mean total choroidal (p=0.0005 and p<0.0001, respectively), luminal (p=0.003 and p<0.0001, respectively) and stromal area (p=0.007 and p=0.0002, respectively) from baseline to month 24; no change of ratio between luminal stromal and the choroidal area was recorded. Mean luminal, stromal and total choroidal areas were reduced in RPD, as compared with drusen and controls at both baseline and month 24 (p<0.05 for all). In RPD, the stromal area was more represented, as we found lower mean ratio of luminal and total choroidal area compared with drusen and control at both baseline and month 24 (p<0.05 for all). CONCLUSIONS: Mean total choroidal, luminal and stromal area decreased over 24 months similarly in eyes with drusen and RPD. Mean total choroidal, luminal and stromal area were more reduced in eyes with RPD, as compared with eyes with drusen and controls; however, stromal area was more represented in eyes with RPD suggesting a possible role of choroidal vascular depletion and fibrotic replacement in the pathogenesis and disease progression. PMID- 27190130 TI - The Swi3 protein plays a unique role in regulating respiration in eukaryotes. AB - Recent experimental evidence increasingly shows that the dysregulation of cellular bioenergetics is associated with a wide array of common human diseases, including cancer, neurological diseases and diabetes. Respiration provides a vital source of cellular energy for most eukaryotic cells, particularly high energy demanding cells. However, the understanding of how respiration is globally regulated is very limited. Interestingly, recent evidence suggests that Swi3 is an important regulator of respiration genes in yeast. In this report, we performed an array of biochemical and genetic experiments and computational analysis to directly evaluate the function of Swi3 and its human homologues in regulating respiration. First, we showed, by computational analysis and measurements of oxygen consumption and promoter activities, that Swi3, not Swi2, regulates genes encoding functions involved in respiration and oxygen consumption. Biochemical analysis showed that the levels of mitochondrial respiratory chain complexes were substantially increased in Deltaswi3 cells, compared with the parent cells. Additionally, our data showed that Swi3 strongly affects haem/oxygen-dependent activation of respiration gene promoters whereas Swi2 affects only the basal, haem-independent activities of these promoters. We found that increased expression of aerobic expression genes is correlated with increased oxygen consumption and growth rates in Deltaswi3 cells in air. Furthermore, using computational analysis and RNAi knockdown, we showed that the mammalian Swi3 BAF155 and BAF170 regulate respiration in HeLa cells. Together, these experimental and computational data demonstrated that Swi3 and its mammalian homologues are key regulators in regulating respiration. PMID- 27190131 TI - Association between selenium levels and oesophageal adenocarcinoma risk: evidence from a meta-analysis. AB - Quantification of the association between selenium and risk of oesophageal adenocarcinoma (OAC) is still conflicting. The purpose of this meta-analysis is to explore the relationship between selenium levels and OAC risk. PubMed and Web of Knowledge were searched for the related articles. Pooled relative risks (RRs) with 95% confidence intervals (CIs) from random effects models were calculated. Sensitivity analysis and publication bias were conducted. Dose-response relationship was assessed by restricted cubic spline and variance-weighted least squares regression analysis. Five articles involving 748 OAC cases were included in this meta-analysis. Pooled results suggest that higher selenium level was not significantly associated with the risk of OAC (summary RRs=1.08, 95% CIs=0.84 1.39, I(2)=0%). Besides, no significant association was found in case-control studies (summary RRs=1.13, 95% CIs=0.84-1.52, I(2)=0%) or cohort studies (summary RRs=0.99, 95% CIs=0.55-1.78, I(2)=32.6%). A linear dose-response relationship was attested that an increase in dietary selenium intake of 10 MUg/day is marginally associated with 1% increase in the risk of developing OAC (summary RRs=1.01, 95% CIs=0.99-1.03), but not statistically significant. No publication bias was found. In conclusion, our analysis indicated that a higher selenium level was not significantly associated with the risk of OAC. The relevant further studies are warranted. PMID- 27190132 TI - A randomised controlled trial comparing skin closure in total knee arthroplasty in the same knee: nylon sutures versus skin staples. AB - OBJECTIVES: Nylon sutures and skin staples are used commonly in total knee arthroplasty (TKA) surgical wound closure. However, there is no study that compares the wound healing efficacy and patient satisfaction scores of both techniques in the same knee. METHODS: We randomised 70 patients who underwent primary TKA into two groups. In one group of 34 patients, the skin at the upper half of the wound was closed with skin staples and the lower half of the wound was closed with simple interrupted nylon sutures. In the other group of 36 patients, the skin at the upper half of the wound was closed with nylon stitches and the lower half of the wound was closed with skin staples. We recorded the wound closure time, pain score at the time of stitch removal, wound complication rate, patient satisfaction score, and the Hollander wound evaluation score at the post-operative periods of five days, 14 days, six weeks, three months, and six months. Each half wound was analysed separately. RESULTS: The mean patient body mass index was 26.8 kg/m(2) (standard deviation 6.3). A total of 70 nylon stitched wounds and 70 skin stapled wounds were analysed. There were no significant differences in wound complication rates, patient satisfaction score, and the Hollander wound evaluation score between both types of wounds (p > 0.05). The wound closure time for skin stapled wounds was significantly lower than the nylon stitched wounds (p < 0.001). However, the skin stapled wounds had a significantly higher pain score at the time of stitch removal (p < 0.001). CONCLUSION: Skin staples and nylon stitches had comparable results with respect to wound healing and patient satisfaction in TKA wound closure in non-obese patients. The benefit of skin staples over nylon stitches was a decrease in operative time, but was more painful upon removal.Cite this article: V. Yuenyongviwat. A randomised controlled trial comparing skin closure in total knee arthroplasty in the same knee: nylon sutures versus skin staples. Bone Joint Res 2016;5:185-190. DOI: 10.1302/2046-3758.55.2000629. PMID- 27190133 TI - Haemostasis with fibrin glue injection into the pericardial space for right ventricular perforation caused by an iatrogenic procedural complication. AB - An 89-year-old woman with severe aortic valve stenosis and bradycardia presented with circulatory shock due to cardiac tamponade. We performed pericardiocentesis, and then diagnosed right ventricular perforation by echocardiography with microcavitation contrast medium just before inserting a drainage tube. We then inserted the drainage tube in the appropriate position and withdrew blood-filled fluid. The patient was haemodynamically stabilised, but haemorrhage from the perforation site continued for a few days. We injected fibrin glue into the pericardial space through the drainage tube and achieved haemostasis. Thus, we avoided surgery to close the perforation in this high-risk patient. There was no recurrence of haemorrhage. She subsequently had elective aortic valve replacement at another hospital. No adhesions in the pericardial space were seen during surgery. PMID- 27190134 TI - Percutaneous coronary intervention in a case of anomalous single coronary artery. AB - Anomalous origin of the right coronary artery is an uncommon entity with a reported incidence of 0.26%. The anomalous origin is usually from the left sinus of Valsalva. Anomalous origin of the right coronary artery (RCA) from the left anterior descending (LAD) artery is a rare occurrence. Symptomatic patients with associated significant coronary artery disease (CAD) may be treated with routine interventions such as percutaneous coronary intervention or coronary artery bypass surgery. We report a case of single coronary artery with severe proximal LAD stenosis. The RCA had its origin from the mid LAD. Coronary intervention was successfully carried out on the severe stenosis at the proximal LAD artery. These cases are rare. We discuss accurate diagnosis and appropriate management in such cases. PMID- 27190135 TI - Cardiac metastatic melanoma. PMID- 27190136 TI - Differential effects of NOX4 and NOX1 on immune cell-mediated inflammation in the aortic sinus of diabetic ApoE-/- mice. AB - Oxidative stress and inflammation are central mediators of atherosclerosis particularly in the context of diabetes. The potential interactions between the major producers of vascular reactive oxygen species (ROS), NADPH oxidase (NOX) enzymes and immune-inflammatory processes remain to be fully elucidated. In the present study we investigated the roles of the NADPH oxidase subunit isoforms, NOX4 and NOX1, in immune cell activation and recruitment to the aortic sinus atherosclerotic plaque in diabetic ApoE(-/-) mice. Plaque area analysis showed that NOX4- and NOX1-derived ROS contribute to atherosclerosis in the aortic sinus following 10 weeks of diabetes. Immunohistochemical staining of the plaques revealed that NOX4-derived ROS regulate T-cell recruitment. In addition, NOX4 deficient mice showed a reduction in activated CD4(+) T-cells in the draining lymph nodes of the aortic sinus coupled with reduced pro-inflammatory gene expression in the aortic sinus. Conversely, NOX1-derived ROS appeared to play a more important role in macrophage accumulation. These findings demonstrate distinct roles for NOX4 and NOX1 in immune-inflammatory responses that drive atherosclerosis in the aortic sinus of diabetic mice. PMID- 27190137 TI - Genome-Wide Analysis of Polycistronic MicroRNAs in Cultivated and Wild Rice. AB - MicroRNAs (miRNAs) are small noncoding RNAs that direct posttranscriptional gene silencing in eukaryotes. They are frequently clustered in the genomes of animals and can be independently transcribed or simultaneously transcribed into single polycistronic transcripts. Only a few miRNA clusters have been described in plants, and most of them are generated from independent transcriptional units. Here, we used a combination of bioinformatic tools and experimental analyses to discover new polycistronic miRNAs in rice. A genome-wide analysis of clustering patterns of MIRNA loci in the rice genome was carried out using a criterion of 3 kb as the maximal distance between two miRNAs. This analysis revealed 28 loci with the ability to form the typical hairpin structure of miRNA precursors in which 2 or more mature miRNAs mapped along the same structure. RT-PCR provided evidence for the polycistronic nature of seven miRNA precursors containing homologous or nonhomologous miRNA species. Polycistronic miRNAs and candidate polycistronic miRNAs are located across different rice chromosomes, except chromosome 12, and resided in both duplicated and nonduplicated chromosomal regions. Finally, most polycistronic and candidate polycistronic miRNAs showed a pattern of conservation in the genome of rice species with an AA genome. The diversity in the organization of MIR genes that are transcribed as polycistrons suggests a versatile mechanism for the control of gene expression in different biological processes and supports additional levels of complexity in miRNA functioning in plants. PMID- 27190139 TI - State of primary care sports and exercise medicine in Brazil. PMID- 27190140 TI - Epidemiology of 3825 injuries sustained in six seasons of National Collegiate Athletic Association men's and women's soccer (2009/2010-2014/2015). AB - AIM: To describe the epidemiology of National Collegiate Athletic Association (NCAA) men's and women's soccer injuries during the 2009/2010-2014/2015 academic years. METHODS: This descriptive epidemiology study used NCAA Injury Surveillance Program (NCAA-ISP) data during the 2009/2010-2014/2015 academic years, from 44 men's and 64 women's soccer programmes (104 and 167 team seasons of data, respectively). Non-time-loss injuries were defined as resulting in <24 h lost from sport. Injury counts, percentages and rates were calculated. Injury rate ratios (RRs) and injury proportion ratios (IPRs) with 95% CIs compared rates and distributions by sex. RESULTS: There were 1554 men's soccer and 2271 women's soccer injuries with injury rates of 8.07/1000 athlete exposures (AE) and 8.44/1000AE, respectively. Injury rates for men and women did not differ in competitions (17.53 vs 17.04/1000AE; RR=1.03; 95% CI 0.94 to 1.13) or practices (5.47 vs 5.69/1000AE; RR=0.96; 95% CI 0.88 to 1.05). In total, 47.2% (n=733) of men's soccer injuries and 47.5% (n=1079) of women's were non-time loss. Most injuries occurred to the lower extremity and were diagnosed as sprains. Women had higher concussion rates (0.59 vs 0.34/1000AE; RR=1.76; 95% CI 1.32 to 2.35) than men. CONCLUSIONS: Non-time-loss injuries accounted for nearly half of the injuries in men's and women's soccer. Sex differences were found in competition injuries, specifically for concussion. Further study into the incidence, treatment and outcome of non-time-loss injuries may identify a more accurate burden of these injuries. PMID- 27190138 TI - An Ancient Transkingdom Horizontal Transfer of Penelope-Like Retroelements from Arthropods to Conifers. AB - Comparative genomics analyses empowered by the wealth of sequenced genomes have revealed numerous instances of horizontal DNA transfers between distantly related species. In eukaryotes, repetitive DNA sequences known as transposable elements (TEs) are especially prone to move across species boundaries. Such horizontal transposon transfers, or HTTs, are relatively common within major eukaryotic kingdoms, including animals, plants, and fungi, while rarely occurring across these kingdoms. Here, we describe the first case of HTT from animals to plants, involving TEs known as Penelope-like elements, or PLEs, a group of retrotransposons closely related to eukaryotic telomerases. Using a combination of in situ hybridization on chromosomes, polymerase chain reaction experiments, and computational analyses we show that the predominant PLE lineage, EN(+)PLEs, is highly diversified in loblolly pine and other conifers, but appears to be absent in other gymnosperms. Phylogenetic analyses of both protein and DNA sequences reveal that conifers EN(+)PLEs, or Dryads, form a monophyletic group clustering within a clade of primarily arthropod elements. Additionally, no EN(+)PLEs were detected in 1,928 genome assemblies from 1,029 nonmetazoan and nonconifer genomes from 14 major eukaryotic lineages. These findings indicate that Dryads emerged following an ancient horizontal transfer of EN(+)PLEs from arthropods to a common ancestor of conifers approximately 340 Ma. This represents one of the oldest known interspecific transmissions of TEs, and the most conspicuous case of DNA transfer between animals and plants. PMID- 27190141 TI - A sulfide:quinone oxidoreductase from Chlorobaculum tepidum displays unusual kinetic properties. AB - Sulfide:quinone oxidoreductase (SQR) is the primary sulfide-oxidizing enzyme found in all three domains of life. Of the six phylogenetically distinct types of SQR, four have representatives that have been biochemically characterized. The genome of Chlorobaculum tepidum encodes three SQR homologs. One of these, encoded by CT1087, is a type VI SQR that has been previously shown to be required for growth at high sulfide concentrations and to be expressed in sulfide-dependent manner. Therefore, CT1087 was hypothesized to be a high sulfide adapted SQR. CT1087 was expressed in Escherichia coli with an N-terminal His-tag (CT1087NHis6) and purified by Ni-NTA chromatography. CT1087NHis6 was active and contained FAD as a strongly bound cofactor. The measured kinetic parameters for CT1087NHis6 indicate a low affinity for sulfide and a high enzymatic turnover rate consistent with the hypothesis for its function inferred from genetic and expression data. These are the first kinetic data for a type VI SQR and have implications for structure-function analyses of all SQR's. PMID- 27190142 TI - The global regulator CodY is required for the fitness of Bacillus cereus in various laboratory media and certain beverages. AB - The impact of gene mutations on the growth of the cells can be studied using pure cultures. However, the importance of certain proteins and pathways can be also examined via co-culturing wild type and its mutant derivative. Here, the relative fitness of a mutant strain that lacks the global nitrogen regulator, CodY, was examined in Bacillus cereus, a food poisoning Gram-positive bacterium. Fitness measurements revealed that the DeltacodY strain was outcompeted when cocultured with the wild-type ATCC 14579 under various rich laboratory medium, and also when inoculated in certain beverages. In nutrient-poor minimal medium, the DeltacodY mutant had comparable fitness to the wild-type strain. Interestingly, the relative fitness of the DeltacodY strain was antagonistic when it was cultivated in apple or orange juices due to unknown properties of these beverages, highlighting the importance of chemical composition of the test medium during the bacterial fitness measurements. PMID- 27190143 TI - Biofilm formation-defective mutants in Pseudomonas putida. AB - Out of 8000 candidates from a genetic screening for Pseudomonas putida KT2442 mutants showing defects in biofilm formation, 40 independent mutants with diminished levels of biofilm were analyzed. Most of these mutants carried insertions in genes of the lap cluster, whose products are responsible for synthesis, export and degradation of the adhesin LapA. All mutants in this class were strongly defective in biofilm formation. Mutants in the flagellar regulatory genes fleQ and flhF showed similar defects to that of the lap mutants. On the contrary, transposon insertions in the flagellar structural genes fliP and flgG, that also impair flagellar motility, had a modest defect in biofilm formation. A mutation in gacS, encoding the sensor element of the GacS/GacA two-component system, also had a moderate effect on biofilm formation. Additional insertions targeted genes involved in cell envelope function: PP3222, encoding the permease element of an ABC-type transporter and tolB, encoding the periplasmic component of the Tol-OprL system required for outer membrane stability. Our results underscore the central role of LapA, suggest cross-regulation between motility and adhesion functions and provide insights on the role of cell envelope trafficking and maintenance for biofilm development in P. putida. PMID- 27190144 TI - Transfer of mupirocin resistance from Staphylococcus haemolyticus clinical strains to Staphylococcus aureus through conjugative and mobilizable plasmids. AB - Coagulase-negative staphylococci are thought to act as reservoirs of antibiotic resistance genes that can be transferred to Staphylococcus aureus, thus hindering the combat of this bacterium. In this work, we analyzed the presence of plasmids conferring resistance to the antibiotic mupirocin-widely used to treat and prevent S. aureus infections in hospital environments-in nosocomial S. haemolyticus strains. About 12% of the 75 strains tested were resistant to mupirocin, and this phenotype was correlated with the presence of plasmids. These plasmids were shown to be diverse, being either conjugative or mobilizable, and capable of transferring mupirocin resistance to S. aureus Our findings reinforce that S. haemolyticus, historically and mistakenly considered as a less important pathogen, is a reservoir of resistance genes which can be transferred to other bacteria, such as S. aureus, emphasizing the necessity of more effective strategies to detect and combat this emergent opportunistic pathogen. PMID- 27190145 TI - Purification, characterization and physiological significance of a chitinase from the pilei of Coprinopsis cinerea fruiting bodies. AB - We purified a chitinase from pilei extractions of Coprinopsis cinerea fruiting bodies by ammonium sulfate precipitation and CM Sepharose cation exchange chromatography. MALDI-TOF/TOF MS analysis characterized this purified chitinase as a putative class V chitinase, ChiB1. ChiB1 hydrolyzed colloidal chitin and chitosan, whereas it did not hydrolyze chitin powder. ChiB1 cleaved only pNP (GlcNAc)2, rather than pNP-GlcNAc or pNP-(Glc-NAc)3, to release nitrophenol. ChiB1 preferably and progressively released (GlcNAc)2 from (GlcNAc)6 and digested (GlcNAc)6 to two molecules of (GlcNAc)3 in a small proportion, but did not split (GlcNAc)2, so it is an exochitinase. ChiB1 has an optimum temperature range of 35 degrees C to 40 degrees C and an optimum pH of 5.0. ChiB1 exhibited Km and Vmax values of 2.63 mg ml(-1) and 2.31 MUmol min(-1) mg protein(-1) for colloidal chitin, respectively. The ChiB1 gene, along with another putative endochitinase (class III chitinase gene), was expressed dominantly among eight predicted chitinase genes in the genome, and its expression level increased with the maturation of fruiting bodies. ChiB1 incubation released a large amount of soluble beta-glucan fractions from alkali-insoluble cell wall fractions of C. cinerea fruiting bodies, thereby it may promote the degradation of cell walls in synergy with the beta-1,3-glucanases during pileus autolysis. PMID- 27190146 TI - Control of Listeria monocytogenes biofilms on industrial surfaces by the bacteriocin-producing Lactobacillus sakei CRL1862. AB - The effect of the bacteriocin-producing Lactobacillus sakei CRL1862 and its bacteriocin in the control of Listeria biofilm formation on industrial surfaces at 10 degrees C was investigated. A screening among different Listeria species was performed allowing selecting L. monocytogenes FBUNT for its use as a biofilm producer on stainless steel (SS) and polytetrafluoroe-thylene (PTFE) surfaces. Three conditions were simulated to evaluate the ability of the bacteriocinogenic strain to displace, exclude and compete pathogen biofilm formation. Lactobacillus sakei CRL1862 effectively inhibited biofilm formation by L. monocytogenes FBUNT through the three assayed mechanisms, pathogen inhibition being more efficient on PTFE than on SS surface. Moreover, co-culture of L. monocytogenes FBUNT with the bacteriocin-producer displayed the highest efficacy reducing the pathogen by 5.54 +/- 0.12 and 4.52 +/- 0.01 on PTFE and SS, respectively. Industrially, the pre treatment with L. sakei CRL1862 or its bacteriocin (exclusion) constitutes the most realistic way to prevent pathogen biofilm settlement. The use of bacteriocins and/or the bacteriocin-producer strain represents a safe and environmentally-friendly sanitation method to mitigate post-processing food contamination. PMID- 27190148 TI - A new lactobacilli in vivo expression system for the production and delivery of heterologous proteins at mucosal surfaces. AB - Food-grade lactic acid bacteria, such as lactobacilli, represent good candidates for the development of mucosal vectors. Indeed, they are generally recognized as safe microorganisms and some strains display beneficial effects (probiotics). In this study, we described a new lactobacilli in vivo expression (LIVE) system for the production and delivery of therapeutic molecules at mucosal surfaces. The versatility and functionality of this system was successfully validated in several lactobacilli species; furthermore, we assessed in vivo LIVE system in two different mouse models of human pathologies: (i) a model of therapy against intestinal inflammation (inflammatory bowel diseases) and (ii) a model of vaccination against dental caries. We demonstrated that Lactobacillus gasseri expressing the anti-inflammatory cytokine IL-10 under LIVE system efficiently delivered the recombinant protein at mucosal surfaces and display anti inflammatory effects. In the vaccination model against caries, LIVE system allowed the heterologous expression of Streptococcus mutans antigen GbpB by L. gasseri, leading to a stimulation of the host immune response. PMID- 27190147 TI - Twitching motility and cAMP levels: signal transduction through a single methyl accepting chemotaxis protein. AB - The Pseudomonas aeruginosa Chp chemosensory system regulates twitching motility, intracellular adenosine 3('') 5(')-cyclic monophosphate (cAMP) levels and is postulated to be involved in directional twitching towards phosphatidylethanolamine (PE). Because PilJ is the only methyl-accepting chemotaxis protein (MCP) identified in the Chp system, we determined the role of PilJ in mediating signal transduction for the distinct outputs of this system. Mutants that lack the periplasmic domain of PilJ (pilJDelta74-273) showed lower levels of cAMP but retained directional twitching towards PE. While initial studies revealed reduced twitching motility by PilJDelta74-273, this was due to decreased cAMP levels. Our data illustrate the importance of the periplasmic domain of PilJ in regulating cAMP. This is the first time a defined domain within PilJ has been identified as having a distinct role in signal transduction. PMID- 27190149 TI - Boric acid-dependent decrease in regulatory histone H3 acetylation is not mutagenic in yeast. AB - Candida albicans is a dimorphic yeast commonly found on human mucosal membranes that switches from yeast to hyphal morphology in response to environmental factors. The change to hyphal growth requires histone H3 modifications by the yeast-specific histone acetyltransferase Rtt109. In addition to its role in morphogenesis, Rtt109-dependent acetylation of histone H3 lysine residues 9 and 56 has regulatory functions during DNA replication and repair. Boric acid (BA) is a broad-spectrum agent that specifically inhibits C. albicans hyphal growth, locking the fungus in its harmless commensal yeast state. The present study characterizes the effect of BA on C. albicans histone acetylation in respect to specificity, time-course and significance. We demonstrate that sublethal concentrations of BA reduce H3K9/H3K56 acetylation, both on a basal level and in response to genotoxic stress. Acetylation at other selected histone sites were not affected by BA. qRT-PCR expression analysis of the DNA repair gene Rad51 indicated no elevated level of genotoxic stress during BA exposure. A forward mutation analysis demonstrated the BA does not increase spontaneous or induced mutations. The findings suggest that DNA repair remains effective even when histone H3 acetylation decreases and dispels the notion that BA treatment impairs genome integrity in yeast. PMID- 27190151 TI - Uptake and effect of rare earth elements on gene expression in Methylosinus trichosporium OB3b. AB - It is well known that Methylosinus trichosporium OB3b has two forms of methane monooxygenase (MMO) responsible for the initial conversion of methane to methanol, a cytoplasmic (soluble) methane monooxygenase and a membrane-associated (particulate) methane monooxygenase, and that copper strongly regulates expression of these alternative forms of MMO. More recently, it has been discovered that M. trichosporium OB3b has multiple types of the methanol dehydrogenase (MeDH), i.e. the Mxa-type MeDH (Mxa-MeDH) and Xox-type MeDH (Xox MeDH), and the expression of these two forms is regulated by the availability of the rare earth element (REE), cerium. Here, we extend these studies and show that lanthanum, praseodymium, neodymium and samarium also regulate expression of alternative forms of MeDH. The effect of these REEs on MeDH expression, however, was only observed in the absence of copper. Further, a mutant of M. trichosporium OB3b, where the Mxa-MeDH was knocked out, was able to grow in the presence of lanthanum, praseodymium and neodymium, but was not able to grow in the presence of samarium. Collectively, these data suggest that multiple levels of gene regulation by metals exist in M. trichosporium OB3b, but that copper overrides the effect of other metals by an as yet unknown mechanism. PMID- 27190150 TI - Bioluminescence-based system for rapid detection of natural transformation. AB - Horizontal gene transfer plays a significant role in bacterial evolution and has major clinical importance. Thus, it is vital to understand the mechanisms and kinetics of genetic transformations. Natural transformation is the driving mechanism for horizontal gene transfer in diverse genera of bacteria. Our study introduces a simple and rapid method for the investigation of natural transformation. This highly sensitive system allows the detection of a transformation event directly from a bacterial population without any separation step or selection of cells. The system is based on the bacterial luciferase operon from Photorhabdus luminescens The studied molecular tools consist of the functional modules luxCDE and luxAB, which involve a replicative plasmid and an integrative gene cassette. A well-established host for bacterial genetic investigations, Acinetobacter baylyi ADP1, is used as the model bacterium. We show that natural transformation followed by homologous recombination or plasmid recircularization can be readily detected in both actively growing and static biofilm-like cultures, including very rare transformation events. The system allows the detection of natural transformation within 1 h of introducing sample DNA into the culture. The introduced method provides a convenient means to study the kinetics of natural transformation under variable conditions and perturbations. PMID- 27190152 TI - Identification of a multidrug efflux pump in Mycobacterium smegmatis. AB - Cell wall impermeability and active efflux of drugs are among the primary reasons for drug resistance in mycobacteria. Efflux pumps are tripartite membrane localized transport proteins that expel drug molecules outside the cells. Several of such efflux pumps are annotated in mycobacteria, but few have been characterized, like MSMEG_2991, a putative efflux pump permease of Mycobacterium smegmatis To substantiate this, we overexpressed MSMEG_2991 protein in Escherichia coli 2443. Expression of MSMEG_2991 elevated the resistance towards structurally unrelated groups of antibiotics. An active antibiotic efflux pump nature of MSMEG_2991 was revealed by assessing the acquisition of ciprofloxacin in the absence and presence of the efflux pump inhibitor, carbonyl cyanide m chlorophenyl hydrazone, indicating the involvement of proton-motive force (pmf) during the efflux activity. MSMEG_2991 expression elevated biofilm formation in E. coli by 4-fold, keeping parity to some of the earlier reported efflux pumps. In silico analysis suggested the presence of 12 transmembrane helices in MSMEG_2991 resembling EmrD efflux pump of E. coli Based on in vivo and in silico analyses, MSMEG_2991 may be designated as a pmf-mediated multidrug efflux pump protein that expels diverse groups of antibiotics and might as well be involved in the biofilm enhancement. PMID- 27190153 TI - Low disease-causing threshold in a frog species susceptible to chytridiomycosis. AB - A simple diagnosis of the presence or absence of an infection is an uninformative metric when individuals differ considerably in their tolerance to different infection loads or resistance to rates of disease progression. Models that incorporate the relationship between the progression of the infection with the potential alternate outcomes provide a far more powerful predictive tool than diagnosis alone. The global decline of amphibians has been amplified by Batrachochytrium dendrobatidis, a pathogen that can cause the fatal disease chytridiomycosis. We measured the infection load and observed signs of disease in Litoria aurea Receiver operating characteristic curves were used to quantify the dissimilarity between the infection loads of L. aurea that showed signs associated with chytridiomycosis and those that did not. Litoria aurea had a 78% probability of developing chytridiomycosis past a threshold of 68 zoospore equivalents (ZE) per swab and chytridiomycosis occurred within a variable range of 0.5-490 ZE. Studies should incorporate a species-specific threshold as a predictor of chytridiomycosis, rather than a binary diagnosis. Measures of susceptibility to chytridiomycosis must account not only for the ability of B. dendrobatidis to increase its abundance on the skin of amphibians but also to determine how each species tolerates these infection loads. PMID- 27190154 TI - Peer review: from recognition to improved practices. AB - Scientific publishing has experienced profound changes in recent years, such as the advent of open-access journals, the increasing use of preprint archives or post-publication blogs, to name a few. One pillar still remains: peer review as a key ingredient that, in most cases, contributes to clarity and quality, often detecting errors and misinterpretations. Unfortunately, peer review is poorly recognized and good reviewers are rather a 'rare avis'. Even worse, this necessary task in science is generally overlooked in curricula and post-graduate education. Some considerations should help us all to ameliorate greatly our understanding and duties. PMID- 27190155 TI - Cytotoxic damage of soybean agglutinin on intestinal epithelial cells of broiler chicks: in vitro protection by Bifidobacterium infantis CRL1395. AB - Plant lectins, which are proteins/glycoproteins present in a wide range of vegetables, fruits, cereals and beans, are resistant to digestive enzymes and food cooking temperatures. They bind reversibly to specific glycosidic residues expressed on the membrane of intestinal epithelial cells (IEC) and cause anti nutritional effects in humans and animals. Soybean lectin (SBA) has been detected in poultry diets, and its ability to bind to the intestinal epithelium has been reported. The development of new methods for removing SBA from feeds or to prevent interaction with the intestinal mucosa is of interest. In this study, the in vitro cytotoxicity of SBA on IEC of chicks was demonstrated for the first time. The LD50, assessed after 2 h exposure of IEC to SBA, was 6.13 MUg mL(-1) The ability of Bifidobacterium infantis CRL1395 to bind SBA on the bacterial envelope was confirmed, and prevention of IEC cytotoxicity by lectin removal was demonstrated. Safety of B. infantis CRL1395, resistance to gastrointestinal stress and adhesion were also determined. It was concluded that the early administration of B. infantis CRL1395 to chicks would effectively reduce the toxicity of SBA. Besides, it would favour the colonization of the gut with a beneficial microbiota. PMID- 27190156 TI - Lichen-forming fungus Caloplaca flavoruscens inhibits transcription factors and chromatin remodeling system in fungi. AB - Lichen-forming fungi and extracts derived from them have been used as alternative medicine sources for millennia and recently there has been a renewed interest in their known bioactive properties for anticancer agents, cosmetics and antibiotics. Although lichen-forming fungus-derived compounds are biologically and commercially valuable, few studies have been performed to determine their modes of action. This study used chemical-genetic and chemogenomic high throughput analyses to gain insight into the modes of action of Caloplaca flavoruscens extracts. High-throughput screening of 575 lichen extracts was performed and 39 extracts were identified which inhibited yeast growth. A C. flavoruscens extract was selected as a promising antifungal and was subjected to genome-wide haploinsufficiency profiling and homozygous profiling assays. These screens revealed that yeast deletion strains lacking Rsc8, Pro1 and Toa2 were sensitive to three concentrations (IC25.5, IC25 and IC50, respectively) of C. flavoruscens extract. Gene-enrichment analysis of the data showed that C. flavoruscens extracts appear to perturb transcription and chromatin remodeling. PMID- 27190157 TI - Impact of pnpR, a LysR-type regulator-encoding gene, on the cellular processes of Pseudomonas putida DLL-E4. AB - LysR-type transcriptional regulators (LTTRs) regulate various cellular processes in bacteria. pnpR is an LTTR-encoding gene involved in the regulation of hydroquinone (HQ) degradation, and its effects on the cellular processes of Pseudomonas putida DLL-E4 were investigated at the physiological, biochemical and molecular levels. Reverse transcription polymerase chain reaction revealed that pnpR positively regulated its own expression and that of the pnpC1C2DECX1X2 operon; additionally, pnpR partially regulated the expression of pnpA when P. putida was grown on para-nitrophenol (PNP) or HQ. Strains DLL-E4 and DLL DeltapnpR exhibited similar cellular morphologies and growth rates. Transcriptome analysis revealed that pnpR regulated the expression of genes in addition to those involved in PNP degradation. A total of 20 genes were upregulated and 19 genes were downregulated by at least 2-fold in strain DLL-DeltapnpR relative to strain DLL-E4. Bioinformatic analysis revealed putative PnpR-binding sites located in the upstream regions of genes involved in PNP degradation, carbon catabolite repression and other cellular processes. The utilization of L-aspartic acid, L-histidine, L-pyroglutamic acid, L-serine, gamma-aminobutyric acid, D,L lactic acid, D-saccharic acid, succinic acid and L-alaninamide was increased at least 1.3-fold in strain DLL-DeltapnpR as shown by BIOLOG assays, indicating that pnpR plays a potential negative regulation role in the utilization of carbon sources. PMID- 27190158 TI - Characterization of three positive regulators for tetramycin biosynthesis in Streptomyces ahygroscopicus. AB - Three putative regulatory genes, namely ttmRI, ttmRII and ttmRIII, which are present in the tetramycin (ttm) biosynthetic gene cluster, were found in Streptomyces ahygroscopicus Disruption of ttmRI, ttmRII or ttmRIII reduced tetramycin production, and their complementation restored production to varying degrees. Gene expression analysis of the wild-type (WT) and mutant strains through reverse transcriptase-polymerase chain reaction (RT-PCR) of the ttm gene cluster showed that the expression levels of most of the biosynthetic genes were reduced in DeltattmRI, DeltattmRII and DeltattmRIII Electrophoretic mobility shift assays demonstrated that TtmRI, TtmRII and TtmRIII bound the promoters of several genes in the ttm gene cluster. This study found that these three proteins are a group of positive regulators that activate the transcription of the ttm gene cluster in S. ahygroscopicus In addition, DeltattmRII had a reduced degree of grey pigmentation. Thus, TtmRII has a pleiotropic regulatory function in the tetramycin biosynthetic pathway and in development. PMID- 27190159 TI - Identification of essential arginine residues of Escherichia coli DedA/Tvp38 family membrane proteins YqjA and YghB. AB - Escherichia coli DedA/Tvp38 family proteins YghB and YqjA are putative membrane transporters with 62% amino acid identity and overlapping functions. An E. coli strain (BC202) with nonpolar DeltayghB and DeltayqjA mutations displays cell division defects and temperature sensitivity and is sensitive to antibiotics and alkaline pH. In this study, we performed site-directed mutagenesis on conserved, charged amino acids of YqjA and YghB. We discovered two conserved predicted membrane-embedded arginines (R130 and R136) that are critical for function in both proteins as defined by their ability to complement BC202 phenotypes, when expressed from a plasmid. Lysine can substitute for arginine at position R130 indicating a charge dependence at this position, but could not substitute at R136. In light of the established role that arginine plays in the translocation mechanism of numerous membrane transporters, we hypothesize that these amino acids play a role in the transport mechanism of these DedA/Tvp38 family proteins. PMID- 27190160 TI - A new biotype of Fusarium oxysporum f. sp. lycopersici race 2 emerged by a transposon-driven mutation of avirulence gene AVR1. AB - Emergence of races in Fusarium oxysporum f. sp. lycopersici (Fol) is caused by loss or mutation of at least one avirulence (AVR) gene. The product of AVR1 is a small protein (Avr1) secreted by Fol in tomato xylem sap during infection. This protein triggers Fol race 1 specific resistance (I) in tomato, indicating that AVR1 is an AVR gene. Deletion of AVR1 in race 1 resulted in the emergence of race 2, and an additional mutation in AVR2 generated race 3. Previously, we reported a new biotype of race 3, KoChi-1, in which AVR1 was truncated by a transposon Hormin, which suggested a new route to evolution of races in Fol However, to date no race 2 isolate carrying Hormin-truncated AVR1 has been reported. In this report, we describe such isolates, represented by Chiba-5, in which Hormin insertion occurred in AVR1 at a position different from that in KoChi-1. AVR1 truncation in both isolates resulted in production of defective Avr1 proteins. Chiba-5 and KoChi-1 belong to different phylogenetic clades, A1 and A2, respectively, suggesting that insertion of Hormin in AVR1 in Chiba-5 and KoChi-1 occurred as independent evolutionary events. PMID- 27190161 TI - A new custom microarray for sRNA profiling in Escherichia coli. AB - Bacterial small RNAs (sRNAs) play essential roles in the post-transcriptional control of gene expression. To improve their detection by conventional microarrays, we designed a custom microarray containing a group of probes targeting known and some putative Escherichia coli sRNAs. To assess its potential in detection of sRNAs, RNA profiling experiments were performed with total RNA extracted from E. coli MG1655 cells exponentially grown in rich (Luria-Bertani) and minimal (M9/glucose) media. We found that many sRNAs could yield reasonably strong and statistically significant signals corresponding to nearly all sRNAs annotated in the EcoCyc database. Besides differential expression of two sRNAs (GcvB and RydB), expression of other sRNAs was less affected by the composition of the growth media. Other examples of the differentially expressed sRNAs were revealed by comparing gene expression of the wild-type strain and its isogenic mutant lacking functional poly(A) polymerase I (pcnB). Further, northern blot analysis was employed to validate these data and to assess the existence of new putative sRNAs. Our results suggest that the use of custom microarrays with improved capacities for detection of sRNAs can offer an attractive opportunity for efficient gene expression profiling of sRNAs and their target mRNAs at the whole transcriptome level. PMID- 27190162 TI - OxyR-regulated catalase activity is critical for oxidative stress resistance, nodulation and nitrogen fixation in Azorhizobium caulinodans. AB - The legume-rhizobial interaction results in the formation of symbiotic nodules in which rhizobia fix nitrogen. During the process of symbiosis, reactive oxygen species (ROS) are generated. Thus, the response of rhizobia to ROS is important for successful nodulation and nitrogen fixation. In this study, we investigated how Azorhizobium caulinodans, a rhizobium that forms both root and stem nodules on its host plant, regulates ROS resistance. We found that in-frame deletions of a gene encoding the putative catalase-peroxidase katG or a gene encoding a LysR family regulatory protein, oxyR, exhibited increased sensitivity to H2O2 We then showed that OxyR positively regulated katG expression in an H2O2-independent fashion. Furthermore, we found that deletion of katG or oxyR led to significant reduction in the number of stem nodules and decrease of nitrogen fixation capacities in symbiosis. Our results revealed that KatG and OxyR are not only critical for antioxidant defense in vitro, but also important for nodule formation and nitrogen fixation during interaction with plant hosts. PMID- 27190163 TI - Plants of the fynbos biome harbour host species-specific bacterial communities. AB - The fynbos biome in South Africa is globally recognised as a plant biodiversity hotspot. However, very little is known about the bacterial communities associated with fynbos plants, despite interactions between primary producers and bacteria having an impact on the physiology of both partners and shaping ecosystem diversity. This study reports on the structure, phylogenetic composition and potential roles of the endophytic bacterial communities located in the stems of three fynbos plants (Erepsia anceps, Phaenocoma prolifera and Leucadendron laureolum). Using Illumina MiSeq 16S rRNA sequencing we found that different subpopulations of Deinococcus-Thermus, Alphaproteobacteria, Acidobacteria and Firmicutes dominated the endophytic bacterial communities. Alphaproteobacteria and Actinobacteria were prevalent in P. prolifera, whereas Deinococcus-Thermus dominated in L. laureolum, revealing species-specific host-bacteria associations. Although a high degree of variability in the endophytic bacterial communities within hosts was observed, we also detected a core microbiome across the stems of the three plant species, which accounted for 72% of the sequences. Altogether, it seems that both deterministic and stochastic processes shaped microbial communities. Endophytic bacterial communities harboured putative plant growth promoting bacteria, thus having the potential to influence host health and growth. PMID- 27190164 TI - Stx1 prophage excision in Escherichia coli strain PA20 confers strong curli and biofilm formation by restoring native mlrA. AB - Prophage insertions in Escherichia coli O157:H7 mlrA contribute to the low expression of curli fimbriae and biofilm observed in many clinical isolates. Varying levels of CsgD-dependent curli/biofilm expression are restored to strains bearing prophage insertions in mlrA by mutation of regulatory genes affecting csgD Our previous study identified strong biofilm- and curli-producing variants in O157:H7 cultures that had lost the mlrA-imbedded prophage characteristic of the parent population, suggesting prophage excision as a mechanism for restoring biofilm properties. In this study, we compared genomic, transcriptomic and phenotypic properties of parent strain PA20 (stx1, stx2) and its prophage-cured variant, 20R2R (stx2), and confirmed the mechanism underlying the differences in biofilm formation. PMID- 27190165 TI - Characterization of LysPBC4, a novel Bacillus cereus-specific endolysin of bacteriophage PBC4. AB - Bacillus cereus is a spore-forming, Gram-positive bacterium and is a major food borne pathogen. A B. cereus-specific bacteriophage PBC4 was isolated from the soil of a stock farm, and its genome was analyzed. PBC4 belongs to the Siphoviridae family and has a genome consisting of 80 647-bp-long double-stranded DNA, including 123 genes and two tRNAs. LysPBC4, the endolysin of PBC4, has an enzymatically active domain (EAD) on its N-terminal region and a putative cell wall-binding domain (CBD) on its C-terminal region, respectively. Although the phage PBC4 showed a very limited host range, LysPBC4 could lyse all of the B. cereus strains tested. However, LysPBC4 did not kill other bacteria such as B. subtilis or Listeria, indicating that the endolysin has specific lytic activity against the B. cereus group species. Furthermore, LysPBC4_CBD fused with enhanced green fluorescent protein (EGFP) could decorate limited strains of B. cereus group, suggesting that the LysPBC4_CBD may be a promising material for specific detection of B. cereus. PMID- 27190167 TI - Bioreactors and in situ product recovery techniques for acetone-butanol-ethanol fermentation. AB - The microbial fermentation process is one of the sustainable and environment friendly ways to produce 1-butanol and other bio-based chemicals. The success of the fermentation process greatly relies on the choice of bioreactors and the separation methods. In this review, the history and the performance of bioreactors for the acetone-butanol-ethanol (ABE) fermentation is discussed. The subject is then focused on in situ product recovery (ISPR) techniques, particularly for the integrated extraction-gas stripping. The usefulness of this promising hybrid ISPR device is acknowledged by its incorporation with batch, fed batch and continuous processes to improve the performance of ABE fermentation. PMID- 27190168 TI - Characterization of Bacillus cereus isolates from local dairy farms in China. AB - Bacillus cereus is an important opportunistic foodborne pathogen. In the present work, a total of 306 milk and environmental samples were collected from 10 local dairy farms in Beijing, China. Of the 92 B. cereus-like isolates, 88 and 4 belonged to B. cereus and B. thuringiensis, respectively. The prevalence of B. cereus isolates in bedding, feces, feed, liquid manure and raw milk was 93.3%, 78.9%, 41.2%, 100.0% and 9.8%, respectively. Three main toxin genes nhe, hbl and ces were detected with rates of 100.0%, 78.3% and 1.1%, but no strain harbored cytK1 The production of Nhe, Hbl and cereulide could be confirmed by specific monoclonal antibodies-based enzyme immunoassays in 94.6%, 70.7% and 1.1% of all isolates, respectively. Cytotoxicity tests were used to further corroborate the results of genetic and protein-based assays; 91.3% of the isolates showed cytotoxicity to Vero cells. All isolates were tested for antimicrobial resistance against 17 antibiotics. All isolates were resistant to lincomycin, retapamulin, tiamulin and valnemulin, while two strains were susceptible to ampicillin and ceftiofur. A total of 16 isolated strains were resistant to tetracycline. Since spores of B. cereus are not inactivated during manufacturing of most milk products, contamination of milk with B. cereus on the farm level may represent a potential hazard, particularly with respect to emetic toxin-producing strains. PMID- 27190169 TI - Dopamine Reuptake Inhibitors in Parkinson's Disease: A Review of Nonhuman Primate Studies and Clinical Trials. AB - Striatal dopamine deficiency is the core feature of the pathology of Parkinson's disease (PD), and dopamine replacement with l-3,4-dihydroxyphenylalanine (l-DOPA) is the mainstay of PD treatment. Unfortunately, chronic l-DOPA administration is marred by the emergence of dyskinesia and wearing-off. Alternatives to l-DOPA for alleviation of parkinsonism are of interest, although none can match the efficacy of l-DOPA to date. Catechol-O-methyltransferase and monoamine oxidase inhibitors are currently used to alleviate wearing-off, but they do not increase "on-time" without exacerbating dyskinesia. Alternate approaches to dopamine replacement in parkinsonism generally (and to wearing-off and dyskinesia, specifically) are therefore urgently needed. Inasmuch as they increase synaptic dopamine levels, dopamine transporter (DAT) inhibitors, whether they are selective or have actions on noradrenaline or serotonin transporters, theoretically represent an attractive way to alleviate parkinsonism per se and potentially enhance l-DOPA antiparkinsonian action (provided that sufficient dopamine terminals remain within the striatum). Several nonhuman primate studies and clinical trials have been performed to evaluate the potential of DAT inhibitors for PD. In this article, we review nonhuman primate studies and clinical trials, we summarize the current knowledge of DAT inhibitors in PD, and we propose a hypothesis as to how tailoring the selectivity of DAT inhibitors might maximize the benefits of DAT inhibition in PD. PMID- 27190166 TI - Comparison of inferred relatedness based on multilocus variable-number tandem repeat analysis and whole genome sequencing of Vibrio cholerae O1. AB - Vibrio cholerae causes cholera, a severe diarrheal disease. Understanding the local genetic diversity and transmission of V. cholerae will improve our ability to control cholera. Vibrio cholerae isolates clustered in genetically related groups (clonal complexes, CC) by multilocus variable tandem-repeat analysis (MLVA) were compared by whole genome sequencing (WGS). Isolates in CC1 had been isolated from two geographical locations. Isolates in a second genetically distinct group, CC2, were isolated only at one location. Using WGS, CC1 isolates from both locations revealed, on average, 43.8 nucleotide differences, while those strains comprising CC2 averaged 19.7 differences. Strains from both MLVA CCs had an average difference of 106.6. Thus, isolates comprising CC1 were more closely related (P < 10(-6)) to each other than to isolates in CC2. Within a MLVA CC, after removing all paralogs, alternative alleles were found in all possible combinations on separate chromosomes indicative of recombination within the core genome. Including recombination did not affect the distinctiveness of the MLVA CCs when measured by WGS. We found that WGS generally reflected the same genetic relatedness of isolates as MLVA, indicating that isolates from the same MLVA-CC shared a more recent common ancestor than isolates from the same location that clustered in a distinct MLVA-CC. PMID- 27190171 TI - Correction to "Combined Antiproliferative Effects of the Aminoalkylindole WIN55,212-2 and Radiation in Breast Cancer Cells". PMID- 27190170 TI - Analysis of beta-Subunit-dependent GABAA Receptor Modulation and Behavioral Effects of Valerenic Acid Derivatives. AB - Valerenic acid (VA)-a beta2/3-selective GABA type A (GABAA) receptor modulator displays anxiolytic and anticonvulsive effects in mice devoid of sedation, making VA an interesting drug candidate. Here we analyzed beta-subunit-dependent enhancement of GABA-induced chloride currents (IGABA) by a library of VA derivatives and studied their effects on pentylenetetrazole (PTZ)-induced seizure threshold and locomotion. Compound-induced IGABA enhancement was determined in oocytes expressing alpha1beta1gamma2S, alpha1beta2gamma2S, or alpha1beta3gamma2S receptors. Effects on seizure threshold and locomotion were studied using C57BL/6N mice and compared with saline-treated controls. beta2/3-selective VA derivatives such as VA-amide (VA-A) modulating alpha1beta3gamma2S (VA-A: Emax = 972 +/- 69%, n = 6, P < 0.05) and alpha1beta2gamma2S receptors (Emax = 1119 +/- 72%, n = 6, P < 0.05) more efficaciously than VA (alpha1beta3gamma2S: VA: Emax = 632 +/- 88%, n = 9 versus alpha1beta2gamma2S: VA: Emax = 721 +/- 68%, n = 6) displayed significantly more pronounced seizure threshold elevation than VA (saline control: 40.4 +/- 1.4 mg/kg PTZ versus VA 10 mg/kg: 49.0 +/- 1.8 mg/kg PTZ versus VA-A 3 mg/kg: 57.9 +/- 1.9 mg/kg PTZ, P < 0.05). Similarly, VA's methylamide (VA-MA) enhancing IGABA through beta3-containing receptors more efficaciously than VA (Emax = 1043 +/- 57%, P < 0.01, n = 6) displayed stronger anticonvulsive effects. Increased potency of IGABA enhancement and anticonvulsive effects at lower doses compared with VA were observed for VA-tetrazole (alpha1beta3gamma2S: VA-TET: EC50 = 6.0 +/- 1.0 MUM, P < 0.05; VA-TET: 0.3 mg/kg: 47.3 +/- 0.5 mg/kg PTZ versus VA: 10 mg/kg: 49.0 +/- 1.8 mg/kg PTZ, P < 0.05). At higher doses (>=10 mg/kg), VA-A, VA-MA, and VA-TET reduced locomotion. In contrast, unselective VA derivatives induced anticonvulsive effects only at high doses (30 mg/kg) or did not display any behavioral effects. Our data indicate that the beta2/3-selective compounds VA-A, VA-MA, and VA-TET induce anticonvulsive effects at low doses (<=10 mg/kg), whereas impairment of locomotion was observed at doses >=10 mg/kg. PMID- 27190174 TI - CardioPulse Articles. PMID- 27190173 TI - Syncope and sudden cardiac death: some answers to clinical challenges. PMID- 27190172 TI - Impact of a Healthcare Provider Educational Intervention on Frequency of Clostridium difficile Polymerase Chain Reaction Testing in Children: A Segmented Regression Analysis. AB - Background.: Although Clostridium difficile infections (CDIs) are increasingly diagnosed in children, many children diagnosed with CDI lack classic risk factors. Frequent use of highly sensitive tcdB polymerase chain reaction (PCR) testing in low-risk patients leads to CDI misdiagnosis and unnecessary CDI antibiotic use in children with C difficile carriage. Methods.: For this quasi experimental study, we developed and implemented an educational intervention (EI) to inform healthcare providers (HCPs) about tcdB PCR test limitations. We provided HCP didactic education and built an electronic notification into the tcdB PCR test order that describes scenarios in which carriage is more likely than CDI. Segmented regression analysis assessed changes in level (ie, overall rates) and trend of C difficile testing rate ([TR] number of tests performed per 1000 patient encounters) and test positivity rate ([PR] number of positive tests per 1000 patient encounters) between the pre- (August 2009-August 2013) and postintervention (February 2014-July 2015) periods. Results.: Hospital-wide, absolute TR reduction was 0.71 (P[level] = .0067; P[trend] = .0042) and absolute PR reduction was 0.14 (P[level] = .22; P[trend] = .018). In the outpatient setting, absolute TR reduction was 0.30 (P[level] = .0015; P[trend] < .001) and absolute PR reduction was 0.09 (P[level] = .0069; P[trend] = .046). The incidence density of healthcare facility-associated CDI did not significantly change after the EI. The EI was associated with avoidance of 574 tests and 113 positive tests (and subsequent antibiotic courses) during the postintervention period, which saved approximately $250 000 in patient charges related to CDI testing and treatment. Conclusions.: Healthcare provider education can cost-effectively reduce the frequency of C difficile testing and CDI misdiagnosis by improving test utilization among low-risk children. PMID- 27190175 TI - STING-Dependent 2'-5' Oligoadenylate Synthetase-Like Production Is Required for Intracellular Mycobacterium leprae Survival. AB - Cytosolic detection of nucleic acids elicits a type I interferon (IFN) response and plays a critical role in host defense against intracellular pathogens. Herein, a global gene expression profile of Mycobacterium leprae-infected primary human Schwann cells identified the genes differentially expressed in the type I IFN pathway. Among them, the gene encoding 2'-5' oligoadenylate synthetase-like (OASL) underwent the greatest upregulation and was also shown to be upregulated in M. leprae-infected human macrophage cell lineages, primary monocytes, and skin lesion specimens from patients with a disseminated form of leprosy. OASL knock down was associated with decreased viability of M. leprae that was concomitant with upregulation of either antimicrobial peptide expression or autophagy levels. Downregulation of MCP-1/CCL2 release was also observed during OASL knock down. M. leprae-mediated OASL expression was dependent on cytosolic DNA sensing mediated by stimulator of IFN genes signaling. The addition of M. leprae DNA enhanced nonpathogenic Mycobacterium bovis bacillus Calmette-Guerin intracellular survival, downregulated antimicrobial peptide expression, and increased MCP 1/CCL2 secretion. Thus, our data uncover a promycobacterial role for OASL during M. leprae infection that directs the host immune response toward a niche that permits survival of the pathogen. PMID- 27190177 TI - Saposin-like Proteins, a Multigene Family of Schistosoma Species, are Biomarkers for the Immunodiagnosis of Schistosomiasis Japonica. AB - BACKGROUND: One major obstacle to schistosomiasis prevention and control is the lack of accurate and sensitive diagnostic approaches, which are essential for planning, targeting, and evaluating disease control efforts. METHODS: Based on bioinformatics analysis, we identified a multigene family of saposin-like protein (SAPLP) in the schistosome genomes. Schistosoma japonicum SAPLPs (SjSAPLPs), including recently reported promising biomarker SjSP-13, were systematically and comparatively assessed as immunodiagnostic antigens for schistosomiasis japonica. RESULTS: Two novel antigens (SjSAPLP4 and SjSAPLP5) could specifically react to serum samples from both S. japonicum-infected laboratory animals and patients. The sensitivities of SjSAPLP4, SjSAPLP5, and SjSP-13 for immunodiagnosis were 98% (95% confidence interval, 88.0%-99.9%), 96% (85.1%-99.3%), and 88% (75.0%-95.0%), respectively, and 100% (91.1%-100%) specificity was observed for the 3 antigens with enzyme-linked immunosorbent assay; there was no cross-reaction with clonorchiosis (0 of 19 patients), echinococcosis (0 of 20 patients), or trichinellosis (0 of 18 patients) for the 3 antigens. Antibodies to the 3 antigens could be detected in the serum samples of rabbits infected with 1000 cercariae as early as 3-4 weeks after infection. CONCLUSIONS: These results suggest that SjSAPLP4 and SjSAPLP5 could serve as novel biomarkers for the immunodiagnosis of schistosomiasis japonica, which will further improve diagnostic sensitivity and specificity. PMID- 27190176 TI - Enhanced Genetic Characterization of Influenza A(H3N2) Viruses and Vaccine Effectiveness by Genetic Group, 2014-2015. AB - BACKGROUND: During the 2014-2015 US influenza season, expanded genetic characterization of circulating influenza A(H3N2) viruses was used to assess the impact of the genetic variability of influenza A(H3N2) viruses on influenza vaccine effectiveness (VE). METHODS: A novel pyrosequencing assay was used to determine genetic group, based on hemagglutinin (HA) gene sequences, of influenza A(H3N2) viruses from patients enrolled at US Influenza Vaccine Effectiveness Network sites. VE was estimated using a test-negative design comparing vaccination among patients infected with influenza A(H3N2) viruses and uninfected patients. RESULTS: Among 9710 enrollees, 1868 (19%) tested positive for influenza A(H3N2) virus; genetic characterization of 1397 viruses showed that 1134 (81%) belonged to 1 HA genetic group (3C.2a) of antigenically drifted influenza A(H3N2) viruses. Effectiveness of 2014-2015 influenza vaccination varied by influenza A(H3N2) virus genetic group from 1% (95% confidence interval [CI], -14% to 14%) against illness caused by antigenically drifted influenza A(H3N2) virus group 3C.2a viruses versus 44% (95% CI, 16%-63%) against illness caused by vaccine-like influenza A(H3N2) virus group 3C.3b viruses. CONCLUSIONS: Effectiveness of 2014 2015 influenza vaccination varied by genetic group of influenza A(H3N2) virus. Changes in HA genes related to antigenic drift were associated with reduced VE. PMID- 27190178 TI - Universal Mass Vaccination Against Rotavirus: Indirect Effects on Rotavirus Infections in Neonates and Unvaccinated Young Infants Not Eligible for Vaccination. AB - BACKGROUND: Rotavirus (RV)-associated infections account for high numbers of hospitalizations in neonates and young infants. Universal mass vaccination (UMV) has been shown to prevent the burden of disease in vaccinated children. METHODS: The present study investigated the long-term effects of UMV on RV-associated hospitalizations in children with particular focus on neonates and young infants (<=42 days old) not eligible for vaccination. Ten years of Austrian surveillance data were compared, including 10 960 laboratory-confirmed RV cases before (prevaccination period [PreVP]) and after (postvaccination period [PostVP]) introduction of UMV. RESULTS: A postvaccination decrease in hospitalized community-acquired RV infections by 89.3% was seen in all age groups, including unvaccinated neonates and young infants. Of the latter, 27.6% had a nosocomial RV infection in PreVP, and 19.3% in PostVP. Overall, the proportion of nosocomial RV infections increased from 5.5% in PreVP to 13.0% in PostVP. Breakthrough infections, usually after incomplete RV vaccination, could be identified in 6.2% of patients. CONCLUSIONS: Unvaccinated neonates and infants <=42 days old may indirectly benefit from UMV by reduction of RV infections. Breakthrough infections underline the importance of early and complete protection by the vaccine. In older patients, heightened awareness of nosocomial RV infections is warranted. Identification of RV reservoirs is also needed. PMID- 27190180 TI - VAR2CSA Domain-Specific Analysis of Naturally Acquired Functional Antibodies to Plasmodium falciparum Placental Malaria. AB - BACKGROUND: Placental malaria is caused by Plasmodium falciparum-infected erythrocytes (IEs) that surface-express VAR2CSA and bind chondroitin sulfate A. The inflammatory response to placenta-sequestered parasites is associated with poor pregnancy outcomes, and protection may be mediated in part by VAR2CSA antibodies that block placental IE adhesion. METHODS: In this study, we used a new approach to assess VAR2CSA domains for functional epitopes recognized by naturally acquired antibodies. Antigen-specific immunoglobulin (Ig) G targeting Duffy binding-like (DBL) domains from different alleles were sequentially purified from plasma pooled from multigravid women and then characterized using enzyme-linked immunosorbent assay, flow cytometry, and antiadhesion assays. RESULTS: Different DBL domain-specific IgGs could react to homologous as well as heterologous antigens and parasites, suggesting that conserved epitopes are shared between allelic variants. Homologous blocking of IE binding was observed with ID1-DBL2-ID2a-, DBL4-, and DBL5-specific IgG (range, 42%-75%), whereas partial cross-inhibition activity was observed with purified IgG specific to ID1 DBL2-ID2a and DBL4 antigens. Plasma retained broadly neutralizing activity after complete depletion of these VAR2CSA specificities. CONCLUSIONS: Broadly neutralizing antibodies of multigravidae are not depleted on VAR2CSA recombinant antigens, and hence development of VAR2CSA vaccines based on a single construct and variant might induce antibodies with limited broadly neutralizing activity. PMID- 27190181 TI - Immunologic Markers of Protection in Leishmania (Viannia) braziliensis Infection: A 5-Year Cohort Study. AB - BACKGROUND: The control of Leishmania braziliensis by individuals with subclinical infection (SC) are unknown. METHODS: A cohort of 308 household contacts (HCs) of patients with cutaneous leishmaniasis (CL) was established in 2010 in an endemic area and followed up for 5 years. Whole-blood cultures stimulated with soluble Leishmania antigen and a Leishmania skin test (LST) were performed in years 0, 2, and 4. The identification of the lymphocyte subsets secreting interferon (IFN) gamma and the ability of monocytes to control Leishmania were determined. RESULTS: During follow-up, 118 subjects (38.3%) had evidence of L. braziliensis infection. Of the HCs, CL was documented in 45 (14.6%), 101 (32.8%) had SC infection, and 162 (52.6%) did not have evidence of exposure to L. braziliensis The ratio of infection to disease was 3.2:1. IFN gamma production, mainly by natural killer cells, was associated with protection, and a positive LST result did not prevent development of disease. Moreover, monocytes from subjects with SC infection were less permissive to parasite penetration and had a greater ability to control L. braziliensis than cells from patients with CL. CONCLUSIONS: Protection against CL was associated with IFN gamma production, negative LST results, impaired ability of Leishmania to penetrate monocytes, and increased ability to control Leishmania growth. PMID- 27190182 TI - Dually Active HIV/HBV Antiretrovirals as Protection Against Incident Hepatitis B Infections: Potential for Prophylaxis. AB - BACKGROUND: Hepatitis B virus (HBV) has a detrimental effect on human immunodeficiency virus (HIV) natural course, and HBV vaccination is less effective in the HIV infected. We examine the protective effect of dually active antiretroviral therapy (DAART) for HIV/HBV (tenofovir, lamivudine, and emtricitabine) in a large cohort encompassing heterosexuals, men who have sex with men, and intravenous drug users who are HIV infected yet susceptible to HBV, with comprehensive follow-up data about risky behavior and immunological profiles. METHODS: We defined an incident HBV infection as the presence of any of HBV serological markers (hepatitis B surface antigen, anti-hepatitis B core antibodies, or HBV DNA) after a negative baseline test result for anti-hepatitis B core antibodies. Patients with positive anti-hepatitis B surface antigen serology were excluded. Cox proportional hazards models were used, with an incident case of HBV infection as the outcome variable. RESULTS: We analyzed 1716 eligible patients from the Swiss HIV Cohort Study with 177 incident HBV cases. DAART was negatively associated with incident HBV infection (hazard ratio [HR], 0.4; 95% confidence interval [CI], .2-.6). This protective association was robust to adjustment (HR, 0.3; 95% CI, .2-.5) for condomless sex, square-root transformed CD4 cell count, drug use, and patient demographics. Condomless sex (HR, 1.9; 95% CI, 1.4-2.6), being a man who has sex with men (2.7; 1.7-4.2), and being an intravenous drug user (3.8; 2.4-6.1) were all associated with a higher hazard of contracting HBV. CONCLUSIONS: Our study suggests that DAART, independently of CD4 cell count and risky behavior, has a potentially strong public health impact, including pre-exposure prophylaxis of HBV coinfection in the HIV infected. PMID- 27190183 TI - Robust Cytokine and Chemokine Response in Nasopharyngeal Secretions: Association With Decreased Severity in Children With Physician Diagnosed Bronchiolitis. AB - BACKGROUND: Bronchiolitis causes substantial disease in young children. Previous findings had indicated that a robust innate immune response was not associated with a poor clinical outcome in bronchiolitis. This study tested the hypothesis that increased concentrations of cytokines and chemokines in nasal wash specimens were associated with decreased severity in bronchiolitis. METHODS: Children <24 months old who presented to the emergency department with signs and symptoms of bronchiolitis were eligible for enrollment. Nasal wash specimens were analyzed for viral pathogens and cytokine/chemokine concentrations. These results were evaluated with regard to disposition. RESULTS: One hundred eleven children with bronchiolitis were enrolled. A viral pathogen was identified in 91.9% of patients (respiratory syncytial virus in 51.4%, human rhinovirus in 11.7%). Higher levels of cytokines and chemokines (interferon [IFN] gamma; interleukin [IL] 4, 15, and 17; CXCL10; and eotaxin) were significantly associated with a decreased risk of hospitalization. IL-17, IL-4, IFN-gamma, and IFN-gamma-inducible protein 10 (CXCL10 or IP-10) remained statistically significant in the multivariate analyses. CONCLUSIONS: The cytokines and chemokines significantly associated with decreased bronchiolitis severity are classified in a wide range of functional groups (T-helper 1 and 2, regulatory, and chemoattractant). The involvement of these functional groups suggest that a broadly overlapping cytokine/chemokine response is required for control of virus-mediated respiratory disease in young children. PMID- 27190179 TI - Baseline Inflammatory Biomarkers Identify Subgroups of HIV-Infected African Children With Differing Responses to Antiretroviral Therapy. AB - BACKGROUND: Identifying determinants of morbidity and mortality may help target future interventions for human immunodeficiency virus (HIV)-infected children. METHODS: CD4(+) T-cell count, HIV viral load, and levels of biomarkers (C reactive protein, tumor necrosis factor alpha [TNF-alpha], interleukin 6 [IL-6], and soluble CD14) and interleukin 7 were measured at antiretroviral therapy (ART) initiation in the ARROW trial (case-cohort design). Cases were individuals who died, had new or recurrent World Health Organization clinical stage 4 events, or had poor immunological response to ART. RESULTS: There were 115 cases (54 died, 45 had World Health Organization clinical stage 4 events, and 49 had poor immunological response) and 485 controls. Before ART initiation, the median ages of cases and controls were 8.2 years (interquartile range [IQR], 4.4-11.4 years) and 5.8 years (IQR, 2.3-9.3 years), respectively, and the median percentages of lymphocytes expressing CD4 were 4% (IQR, 1%-9%) and 13% (IQR, 8%-18%), respectively. In multivariable logistic regression, cases had lower age associated CD4(+) T-cell count ratio (calculated as the ratio of the subject's CD4(+) T-cell count to the count expected in healthy individuals of the same age; P < .0001) and higher IL-6 level (P = .002) than controls. Clustering biomarkers and age-associated CD4(+) and CD8(+) T-cell count ratios identified 4 groups of children. Group 1 had the highest frequency of cases (41% cases; 16% died) and profound immunosuppression; group 2 had similar mortality (23% cases; 15% died), but children were younger, with less profound immunosuppression and high levels of inflammatory biomarkers and malnutrition; group 3 comprised young children with moderate immunosuppression, high TNF-alpha levels, and high age-associated CD8(+) T-cell count ratios but lower frequencies of events (12% cases; 7% died); and group 4 comprised older children with low inflammatory biomarker levels, lower HIV viral loads, and good clinical outcomes (11% cases; 5% died). CONCLUSIONS: While immunosuppression is the major determinant of poor outcomes during ART, baseline inflammation is an additional important factor, identifying a subgroup of young children with similar mortality. Antiinflammatory interventions may help improve outcomes. PMID- 27190184 TI - Streptococcus oralis and Candida albicans Synergistically Activate MU-Calpain to Degrade E-cadherin From Oral Epithelial Junctions. AB - Streptococcus oralis forms robust mucosal biofilms with Candida albicans that have increased pathogenic potential. In this study, using oral epithelial cultures, organotypic oral mucosal constructs, and a mouse model of oral infection, we demonstrated that S. oralis augmented C. albicans invasion through epithelial junctions. C. albicans and S. oralis decreased epithelial E-cadherin levels by synergistically increasing u-calpain, a proteolytic enzyme that targets E-cadherin. In the mouse coinfection model this was accompanied by increased fungal kidney dissemination. Coinfection with a secreted aspartyl protease (sap) mutant sap2456 and S. oralis increased MU-calpain and triggered mucosal invasion and systemic dissemination, suggesting that fungal protease activity is not required for invasion during coinfection. We conclude that C. albicans and S. oralis synergize to activate host enzymes that cleave epithelial junction proteins and increase fungal invasion. PMID- 27190185 TI - Genital Anaerobic Bacterial Overgrowth and the PrePex Male Circumcision Device, Rakai, Uganda. AB - The PrePex circumcision device causes ischemic necrosis of the foreskin, raising concerns of anaerobic overgrowth. We compared the subpreputial microbiome of 2 men 7 days after PrePex device placement to that of 145 uncircumcised men in Rakai, Uganda, using 16S ribosomal (rRNA) RNA gene-based quantitative polymerase chain reaction analysis and sequencing. PrePex users had higher absolute abundance of all bacteria than uncircumcised men (P = .001), largely due to increased numbers of the following anaerobes: Porphyromonas (5.2 * 10(7) 16S rRNA gene copies/swab in the PrePex group and 1.1 * 10(6) 16S rRNA gene copies/swab in uncircumcised men; P = .002), Peptoniphilus (1.0 * 10(7) and 1.8 * 10(6) 16S rRNA gene copies/swab, respectively; P < .05), Anaerococcus (1.0 * 10(7) and 1.1 * 10(6) 16S rRNA gene copies/swab, respectively; P < .001), and Campylobacter ureolyticus (1.7 * 10(5) and 1.6 * 10(7)16S rRNA gene copies/swab, respectively; P < .001). The PrePex-associated increase in anaerobes may account for unpleasant odor and a possible heightened risk of tetanus. PMID- 27190186 TI - Therapeutic Effect of Recombinant Mutated Interleukin 11 in the Mouse Model of Tuberculosis. AB - Earlier we demonstrated that blocking of interleukin 11 (IL-11) by systemic administration of anti-IL-11 antibodies attenuates severity of Mycobacterium tuberculosis infection in mice. The substitution W147A in the IL-11 molecule creates the form of cytokine capable to disrupt gp130/IL11R signaling complex formation, thus serving as a high-affinity specific antagonist of IL-11-mediated signaling. We hypothesized that this mutant form of IL-11 may serve as an effective tool for inhibition of native IL-11 activity in vivo. We established the recombinant W147A mutant form of IL-11 in an optimized Escherichia coli expression system and administered it as the aerosol in the lungs of M. tuberculosis-susceptible I/St mice infected with M. tuberculosis Our results show that this therapeutic approach markedly inhibits tuberculous inflammation in lungs, increases the survival time of infected animals, and decreases expression of key inflammatory factors at the RNA and protein levels. These findings are a step toward clinical evaluation of the anti-IL-11 therapy for tuberculosis. PMID- 27190188 TI - T-705 as a Potential Therapeutic Agent for Rabies. PMID- 27190187 TI - Bioaerosol Sampling in Modern Agriculture: A Novel Approach for Emerging Pathogen Surveillance? AB - BACKGROUND: Modern agricultural practices create environmental conditions conducive to the emergence of novel pathogens. Current surveillance efforts to assess the burden of emerging pathogens in animal production facilities in China are sparse. In Guangdong Province pig farms, we compared bioaerosol surveillance for influenza A virus to surveillance in oral pig secretions and environmental swab specimens. METHODS: During the 2014 summer and fall/winter seasons, we used 3 sampling techniques to study 5 swine farms weekly for influenza A virus. Samples were molecularly tested for influenza A virus, and positive specimens were further characterized with culture. Risk factors for influenza A virus positivity for each sample type were assessed. RESULTS: Seventy-one of 354 samples (20.1%) were positive for influenza A virus RNA by real-time reverse transcription polymerase chain reaction analysis. Influenza A virus positivity in bioaerosol samples was a statistically significant predictor for influenza A virus positivity in pig oral secretion and environmental swab samples. Temperature of <20 degrees C was a significant predictor of influenza A virus positivity in bioaerosol samples. DISCUSSIONS: Climatic factors and routine animal husbandry practices may increase the risk of human exposure to aerosolized influenza A viruses in swine farms. Data suggest that bioaerosol sampling in pig barns may be a noninvasive and efficient means to conduct surveillance for novel influenza viruses. PMID- 27190190 TI - Reply to Virojanapirom et al. PMID- 27190189 TI - A High-Resolution Look at Influenza Virus Antigenic Drift. PMID- 27190192 TI - Adaptation Helps Fish Thrive in Toxic Environments. PMID- 27190191 TI - Genetic Evolution of a Helicobacter pylori Acid-Sensing Histidine Kinase and Gastric Disease. AB - Helicobacter pylori is the strongest risk factor for gastric adenocarcinoma, which develops within a hypochlorhydric environment. We sequentially isolated H. pylori (strain J99) from a patient who developed corpus-predominant gastritis and hypochlorhydia over a 6-year interval. Archival J99 survived significantly better under acidic conditions than recent J99 strains. H. pylori arsRS encodes a 2 component system critical for stress responses; recent J99 isolates harbored 2 nonsynonymous arsS mutations, and arsS inactivation abolished acid survival. In vivo, acid-resistant archival, but not recent J99, successfully colonized high acid-secreting rodents. Thus, genetic evolution of arsS may influence progression to hypochlorhydia and gastric cancer. PMID- 27190193 TI - When Silent Mutations Provide Evolutionary Advantages. PMID- 27190199 TI - Three-dimensional computed tomography imaging of the mitral valve with huge vegetation. PMID- 27190198 TI - Moderate hypothermia >=24 and <=28 degrees C with hypothermic circulatory arrest for proximal aortic operations in patients with previous cardiac surgery. AB - OBJECTIVES: To determine whether, in patients with previous cardiac operations, moderate hypothermia (between 24 and 28 degrees C) for hypothermic circulatory arrest (HCA) during antegrade cerebral perfusion (ACP) is safe for use during surgery on the proximal aorta and transverse aortic arch. METHODS: Over a 7-year period, 118 patients underwent ascending aortic and hemiarch repair (n = 70; 59.3%), total arch replacement (n = 47; 39.8%) or ascending aortic replacement to treat porcelain aorta (n = 1; 0.9%). Simultaneous procedures included aortic root repair or replacement (n = 33; 28.0%) and coronary artery bypass grafting (n = 21; 17.8%). All patients had previously undergone cardiac operations via a median sternotomy. Eighteen patients (15.3%) had more than 1 previous sternotomy, and 24 patients (20.3%) required emergent/urgent operation. Median cardiopulmonary bypass, cardiac ischaemic, circulatory arrest and ACP times (min) were 136.0 [118 180 interquartile range (IQR)], 91.0 (68-119 IQR), 34.0 (21-59 IQR) and 33.5 (20 59 IQR), respectively. The median temperature when HCA was initiated was 24.2 degrees C (24.1-24.8 degrees C IQR). RESULTS: The operative mortality rate was 10.2% (n = 12). Six patients (5.1%) had a permanent stroke, and 16 patients (13.6%) had a composite adverse outcome (operative mortality and/or a permanent neurological event and/or permanent haemodialysis at discharge). Preoperative renal disease was significantly more prevalent (P= 0.020) and the median circulatory arrest time significantly longer (48.5 vs 33 min; P= 0.058) in patients with composite adverse outcomes. Multivariable analysis of the redo patients showed that age (P =0.025), preoperative renal disease (P =0.024) and ACP time (P =0.012) were independent risk factors for a new postoperative renal injury. CONCLUSIONS: Moderate hypothermia for HCA during ACP is being used with increasing frequency, but has not been thoroughly evaluated in patients undergoing cardiovascular reoperations. Our experience suggests that in patients with previous cardiac surgery who are undergoing hemiarch and total aortic arch operations, moderate hypothermia is safe and produces respectable results. PMID- 27190200 TI - Small bowel obstruction 5 years following the ingestion of serrated scissors. AB - Ingested foreign bodies are common in the cohort of psychiatric patients, however clinical quiescence in this group is rare. We present a case of a 45-year-old female with emotionally unstable personality disorder (borderline type) presenting with partial intestinal obstruction 5 years after the known ingestion of serrated metallic scissors. In the asymptomatic interim a conservative approach of tracking the blades radiologically was taken. Following discussion, we conclude the following: early surgical intervention is encouraged if natural passage does not occur within 3 days following ingestion, and that any concurrent surgical needs should be addressed at this time. PMID- 27190201 TI - A rare case of occult splenic rupture after left pneumonectomy. AB - Cardiopulmonary resuscitation (CPR) techniques are now well-established and play a crucial role in improving survival in cardiac arrest. Recognized complications associated with CPR include injury to the upper abdominal viscera, including the liver, stomach and spleen. We present a rare case of occult splenic rupture following cardiac arrest in a 63-year-old male immediately after left pneumonectomy. We discuss potential mechanisms predisposing the spleen to injury in this case, and highlight the difficulty of promptly identifying such a traumatic injury within the confines of a cardiac arrest scenario. Clinicians should be aware that anatomical changes following thoracic surgery may render the intra-abdominal viscera at increased risk of injury following CPR. PMID- 27190202 TI - Examine the patient not the hernia: identification of an asymptomatic giant primary retroperitoneal pseudocyst. A case report and literature review. AB - We present the case of a 70-year-old man with a giant right-sided retroperitoneal pseudocyst, confirmed histologically after resection to be benign with appearances dissimilar to pancreatic and adrenal tissue. The cyst was noted incidentally on table at the time of laparoscopic surgery. Retroperitoneal pseudocysts most commonly arise from the pancreas and adrenal glands occurring as a result of an inflammatory process. Primary retroperitoneal pseudocysts are a rare entity. This case highlights the importance of examining the patient thoroughly and not focusing on the obvious. The mass was not palpated on initial review prior to listing for surgery, and the patient was asymptomatic from the mass. PMID- 27190204 TI - Population and Evolutionary Genomics of Amblyomma americanum, an Expanding Arthropod Disease Vector. AB - The lone star tick, Amblyomma americanum, is an important disease vector and the most frequent tick found attached to humans in the eastern United States. The lone star tick has recently experienced a rapid range expansion into the Northeast and Midwest, but despite this emerging infectious threat to wildlife, livestock, and human health, little is known about the genetic causes and consequences of the geographic expansion. In the first population genomic analysis of any tick species, we characterize the genetic diversity and population structure of A. americanum across its current geographic range, which has recently expanded. Using a high-throughput genotyping-by-sequencing approach, we discovered more than 8,000 single nucleotide polymorphisms in 90 ticks from five locations. Surprisingly, newly established populations in New York (NY) and Oklahoma (OK) are as diverse as historic range populations in North and South Carolina. However, substantial population structure occurs among regions, such that new populations in NY and OK are genetically distinct from historic range populations and from one another. Ticks from a laboratory colony are genetically distinct from wild populations, underscoring the need to account for natural variation when conducting transmission or immunological studies, many of which utilize laboratory-reared ticks. An FST-outlier analysis comparing a recently established population to a long-standing population detected numerous outlier sites, compatible with positive and balancing selection, highlighting the potential for adaptation during the range expansion. This study provides a framework for applying high-throughput DNA sequencing technologies for future investigations of ticks, which are common vectors of diseases. PMID- 27190203 TI - Parallel Evolution in Streptococcus pneumoniae Biofilms. AB - Streptococcus pneumoniae is a commensal human pathogen and the causative agent of various invasive and noninvasive diseases. Carriage of the pneumococcus in the nasopharynx is thought to be mediated by biofilm formation, an environment where isogenic populations frequently give rise to morphological colony variants, including small colony variant (SCV) phenotypes. We employed metabolic characterization and whole-genome sequencing of biofilm-derived S. pneumoniae serotype 22F pneumococcal SCVs to investigate diversification during biofilm formation. Phenotypic profiling revealed that SCVs exhibit reduced growth rates, reduced capsule expression, altered metabolic profiles, and increased biofilm formation compared to the ancestral strain. Whole-genome sequencing of 12 SCVs from independent biofilm experiments revealed that all SCVs studied had mutations within the DNA-directed RNA polymerase delta subunit (RpoE). Mutations included four large-scale deletions ranging from 51 to 264 bp, one insertion resulting in a coding frameshift, and seven nonsense single-nucleotide substitutions that result in a truncated gene product. This work links mutations in the rpoE gene to SCV formation and enhanced biofilm development in S. pneumoniae and therefore may have important implications for colonization, carriage, and persistence of the organism. Furthermore, recurrent mutation of the pneumococcal rpoE gene presents an unprecedented level of parallel evolution in pneumococcal biofilm development. PMID- 27190205 TI - The Genome of Haemoproteus tartakovskyi and Its Relationship to Human Malaria Parasites. AB - The phylogenetic relationships among hemosporidian parasites, including the origin of Plasmodium falciparum, the most virulent malaria parasite of humans, have been heavily debated for decades. Studies based on multiple-gene sequences have helped settle many of these controversial phylogenetic issues. However, denser taxon sampling and genome-wide analyses are needed to confidently resolve the evolutionay relationships among hemosporidian parasites. Genome sequences of several Plasmodium parasites are available but only for species infecting primates and rodents. To root the phylogenetic tree of Plasmodium, genomic data from related parasites of birds or reptiles are required. Here, we use a novel approach to isolate parasite DNA from microgametes and describe the first genome of a bird parasite in the sister genus to Plasmodium, Haemoproteus tartakovskyi Similar to Plasmodium parasites, H. tartakovskyi has a small genome (23.2 Mb, 5,990 genes) and a GC content (25.4%) closer to P. falciparum (19.3%) than to Plasmodium vivax (42.3%). Combined with novel transcriptome sequences of the bird parasite Plasmodium ashfordi, our phylogenomic analyses of 1,302 orthologous genes demonstrate that mammalian-infecting malaria parasites are monophyletic, thus rejecting the repeatedly proposed hypothesis that the ancestor of Laverania parasites originated from a secondary host shift from birds to humans. Genes and genomic features previously found to be shared between P. falciparum and bird malaria parasites, but absent in other mammal malaria parasites, are therefore signatures of maintained ancestral states. We foresee that the genome of H. tartakovskyi will open new directions for comparative evolutionary analyses of malarial adaptive traits. PMID- 27190207 TI - Higher diurnal salivary cortisol levels are related to smaller prefrontal cortex surface area in elderly men and women. AB - OBJECTIVE: Elevated cortisol levels with aging have been associated with atrophy of the hippocampus and prefrontal cortex (PFC), as well as with impaired cognitive functions in men. However, coexisting diseases have confounded many studies examining these relationships. Studies in women are lacking. Our objective was to test whether salivary cortisol levels were related to morphology of the hippocampus and the PFC, and to cognitive performance. DESIGN: A cross sectional study including 200 elderly (55-80 years old) men and women. METHOD: We used magnetic resonance imaging, tests of episodic-, semantic-, and working memory, visuospatial ability, and cortisol levels in four saliva samples collected during 1 day. RESULTS: Area under the curve (AUC) for cortisol levels was negatively related to cortical surface area of the left anterior cingulate gyrus (caudal P<0.001; rostral P=0.006), right lateral orbitofrontal cortex (P=0.004), and right rostral middle frontal gyrus (P=0.003). In women, there was also a negative relationship with cortical surface area in the left rostral middle frontal gyrus (P=0.006). No relationship was found between cortisol levels and hippocampal volume. CONCLUSION: This study suggests that the structure of the medial PFC is related to cortisol levels in both elderly women and men. PMID- 27190206 TI - "Every Gene Is Everywhere but the Environment Selects": Global Geolocalization of Gene Sharing in Environmental Samples through Network Analysis. AB - The spatial distribution of microbes on our planet is famously formulated in the Baas Becking hypothesis as "everything is everywhere but the environment selects." While this hypothesis does not strictly rule out patterns caused by geographical effects on ecology and historical founder effects, it does propose that the remarkable dispersal potential of microbes leads to distributions generally shaped by environmental factors rather than geographical distance. By constructing sequence similarity networks from uncultured environmental samples, we show that microbial gene pool distributions are not influenced nearly as much by geography as ecology, thus extending the Bass Becking hypothesis from whole organisms to microbial genes. We find that gene pools are shaped by their broad ecological niche (such as sea water, fresh water, host, and airborne). We find that freshwater habitats act as a gene exchange bridge between otherwise disconnected habitats. Finally, certain antibiotic resistance genes deviate from the general trend of habitat specificity by exhibiting a high degree of cross habitat mobility. The strong cross-habitat mobility of antibiotic resistance genes is a cause for concern and provides a paradigmatic example of the rate by which genes colonize new habitats when new selective forces emerge. PMID- 27190209 TI - From Newborn to Senescence Morphological and Functional Remodeling Leads to Increased Contractile Capacity of Arteries. AB - Aging induces substantial morphological and functional changes in vessels. We hypothesized that due to morphological remodeling the total contractile forces of arteries increase, especially in older age as a function of age. Mean arterial blood pressure of rats and morphological and functional characteristics of isolated carotid arteries rats, from newborn to senescent, were assessed. The arterial blood pressure of rats increased significantly from 0.25 to the age of 6 months, and then it reached a level, which was maintained until age of 30 months. Wall lumen and wall thickness increased with age, mostly due to media (smooth muscle) thickening, whereas wall tension gradually reduced with age. Contractions of arteries to nonreceptor-mediated vasomotor agent (KCl, 60mM) increased in three consecutive age groups, whereas contractility first increased (until 2 months), then it did not change further with aging. Norepinephrine-induced contractions initially increased in young age and then did not change further in older age. These findings suggest that during normal aging due to remodeling of arterial wall (smooth muscle) the contractile capacity of arteries increases, which seems to be independent from systemic blood pressure. Thus, arterial remodeling can favor the development of increased circulatory resistance in older age. PMID- 27190208 TI - Gonadal macrophage infiltration in congenital lipoid adrenal hyperplasia. AB - OBJECTIVE: Congenital lipoid adrenal hyperplasia (lipoid CAH) results in impairment of adrenal and gonadal steroidogenesis caused by STAR mutations. Our previous study revealed upregulation of genes associated with inflammatory or immune response and macrophage infiltration in the adrenal cortex of Star knockout mice. This study aimed at investigating macrophage infiltration in the gonads from human patients with lipoid CAH. DESIGN: This study includes seven patients with lipoid CAH who underwent gonadectomy: two XX women (age, 22 and 40 years) and five XY boys (1 year). Two women with ovarian cysts (32 and 40 years) and six boys with autopsy or tumor (1 year) were examined as controls. Immunohistochemical analysis of their gonads was performed to determine steroidogenic cells by NR5A1 or CYP17A1 and macrophages by IBA1 or CD68. RESULTS: An increased number of macrophages infiltrated into the ovaries of lipoid CAH and consisted of two subpopulations: one scattered within and around a layer of theca cells of maturing follicles and the other massively aggregated in the stroma. Abundant cytoplasmic lipid droplets were observed not only in the theca cells but also in the stromal macrophages. There was no significant difference in the number of macrophages in the testicular interstitium between lipoid CAH (95% confidence interval (95% CI: 19.3-47.7 per 0.2mm(2)) and controls (95% CI: 13.3 25.8 per 0.2mm(2)) (P=0.10). CONCLUSIONS: These results demonstrate that macrophages infiltrate the ovaries of lipoid CAH, where the theca cells and the stromal macrophages have abundant cytoplasmic lipid droplets. PMID- 27190210 TI - Understanding the Bases of Function and Modulation of alpha7 Nicotinic Receptors: Implications for Drug Discovery. AB - The nicotinic acetylcholine receptor (nAChR) belongs to a superfamily of pentameric ligand-gated ion channels involved in many physiologic and pathologic processes. Among nAChRs, receptors comprising the alpha7 subunit are unique because of their high Ca(2+) permeability and fast desensitization. nAChR agonists elicit a transient ion flux response that is further sustained by the release of calcium from intracellular sources. Owing to the dual ionotropic/metabotropic nature of alpha7 receptors, signaling pathways are activated. The alpha7 subunit is highly expressed in the nervous system, mostly in regions implicated in cognition and memory and has therefore attracted attention as a novel drug target. Additionally, its dysfunction is associated with several neuropsychiatric and neurologic disorders, such as schizophrenia and Alzheimer's disease. alpha7 is also expressed in non-neuronal cells, particularly immune cells, where it plays a role in immunity, inflammation, and neuroprotection. Thus, alpha7 potentiation has emerged as a therapeutic strategy for several neurologic and inflammatory disorders. With unique activation properties, the receptor is a sensitive drug target carrying different potential binding sites for chemical modulators, particularly agonists and positive allosteric modulators. Although macroscopic and single-channel recordings have provided significant information about the underlying molecular mechanisms and binding sites of modulatory compounds, we know just the tip of the iceberg. Further concerted efforts are necessary to effectively exploit alpha7 as a drug target for each pathologic situation. In this article, we focus mainly on the molecular basis of activation and drug modulation of alpha7, key pillars for rational drug design. PMID- 27190211 TI - Temperature Effects on Kinetics of KV11.1 Drug Block Have Important Consequences for In Silico Proarrhythmic Risk Prediction. AB - Drug block of voltage-gated potassium channel subtype 11.1 human ether-a-go-go related gene (Kv11.1) (hERG) channels, encoded by the KCNH2 gene, is associated with reduced repolarization of the cardiac action potential and is the predominant cause of acquired long QT syndrome that can lead to fatal cardiac arrhythmias. Current safety guidelines require that potency of KV11.1 block is assessed in the preclinical phase of drug development. However, not all drugs that block KV11.1 are proarrhythmic, meaning that screening on the basis of equilibrium measures of block can result in high attrition of potentially low risk drugs. The basis of the next generation of drug-screening approaches is set to be in silico risk prediction, informed by in vitro mechanistic descriptions of drug binding, including measures of the kinetics of block. A critical issue in this regard is characterizing the temperature dependence of drug binding. Specifically, it is important to address whether kinetics relevant to physiologic temperatures can be inferred or extrapolated from in vitro data gathered at room temperature in high-throughout systems. Here we present the first complete study of the temperature-dependent kinetics of block and unblock of a proarrhythmic drug, cisapride, to KV11.1. Our data highlight a complexity to binding that manifests at higher temperatures and can be explained by accumulation of an intermediate, non-blocking encounter-complex. These results suggest that for cisapride, physiologically relevant kinetic parameters cannot be simply extrapolated from those measured at lower temperatures; rather, data gathered at physiologic temperatures should be used to constrain in silico models that may be used for proarrhythmic risk prediction. PMID- 27190212 TI - Cryo-EM Analysis of the Conformational Landscape of Human P-glycoprotein (ABCB1) During its Catalytic Cycle. AB - The multidrug transporter P-glycoprotein (P-gp, ABCB1) is an ATP-dependent pump that mediates the efflux of structurally diverse drugs and xenobiotics across cell membranes, affecting drug pharmacokinetics and contributing to the development of multidrug resistance. Structural information about the conformational changes in human P-gp during the ATP hydrolysis cycle has not been directly demonstrated, although mechanistic information has been inferred from biochemical and biophysical studies conducted with P-gp and its orthologs, or from structures of other ATP-binding cassette transporters. Using single-particle cryo-electron microscopy, we report the surprising discovery that, in the absence of the transport substrate and nucleotides, human P-gp can exist in both open [nucleotide binding domains (NBDs) apart; inward-facing] and closed (NBDs close; outward-facing) conformations. We also probe conformational states of human P-gp during the catalytic cycle, and demonstrate that, following ATP hydrolysis, P-gp transitions through a complete closed conformation to a complete open conformation in the presence of ADP. PMID- 27190213 TI - IL15 promotes growth and invasion of endometrial stromal cells and inhibits killing activity of NK cells in endometriosis. AB - Endometriosis (EMS) is associated with an abnormal immune response to endometrial cells, which can facilitate the implantation and proliferation of ectopic endometrial tissues. It has been reported that human endometrial stromal cells (ESCs) express interleukin (IL)15. The aim of our study was to elucidate whether or not IL15 regulates the cross talk between ESCs and natural killer (NK) cells in the endometriotic milieu and, if so, how this regulation occurs. The ESC behaviors in vitro were verified by Cell Counting Kit-8 (CCK-8), Annexin/PI, and Matrigel invasion assays, respectively. To imitate the local immune microenvironment, the co-culture system between ESCs and NK cells was constructed. The effect of IL15 on NK cells in the co-culture unit was investigated by flow cytometry (FCM). In this study, we found that ectopic endometrium from patients with EMS highly expressed IL15. Rapamycin, an autophagy inducer, decreased the level of IL15 receptors (i.e. IL15Ralpha and IL2Rbeta). IL15 inhibits apoptosis and promotes the invasiveness, viability, and proliferation of ESCs. Meanwhile, a co-culture with ESCs led to a decrease in CD16 on NK cells. In the co-culture system, IL15 treatment downregulated the levels of Granzyme B and IFN-gamma in CD16(+)NK cells, NKG2D in CD56(dim)CD16( )NK cells, and NKP44 in CD56(bright)CD16(-)NK cells. On the one hand, these results indicated that IL15 derived from ESCs directly stimulates the growth and invasion of ESCs. On the other hand, IL15 may help the immune escape of ESCs by suppressing the cytotoxic activity of NK cells in the ectopic milieu, thereby facilitating the progression of EMS. PMID- 27190214 TI - Status of the Archaeal and Bacterial Census: an Update. AB - A census is typically carried out for people across a range of geographical levels; however, microbial ecologists have implemented a molecular census of bacteria and archaea by sequencing their 16S rRNA genes. We assessed how well the census of full-length 16S rRNA gene sequences is proceeding in the context of recent advances in high-throughput sequencing technologies because full-length sequences are typically used as references for classification of the short sequences generated by newer technologies. Among the 1,411,234 and 53,546 full length bacterial and archaeal sequences, 94.5% and 95.1% of the bacterial and archaeal sequences, respectively, belonged to operational taxonomic units (OTUs) that have been observed more than once. Although these metrics suggest that the census is approaching completion, 29.2% of the bacterial and 38.5% of the archaeal OTUs have been observed more than once. Thus, there is still considerable diversity to be explored. Unfortunately, the rate of new full-length sequences has been declining, and new sequences are primarily being deposited by a small number of studies. Furthermore, sequences from soil and aquatic environments, which are known to be rich in bacterial diversity, represent only 7.8 and 16.5% of the census, while sequences associated with host-associated environments represent 55.0% of the census. Continued use of traditional approaches and new technologies such as single-cell genomics and short-read assembly are likely to improve our ability to sample rare OTUs if it is possible to overcome this sampling bias. The success of ongoing efforts to use short-read sequencing to characterize archaeal and bacterial communities requires that researchers strive to expand the depth and breadth of this census. IMPORTANCE: The biodiversity contained within the bacterial and archaeal domains dwarfs that of the eukaryotes, and the services these organisms provide to the biosphere are critical. Surprisingly, we have done a relatively poor job of formally tracking the quality of the biodiversity as represented in full-length 16S rRNA genes. By understanding how this census is proceeding, it is possible to suggest the best allocation of resources for advancing the census. We found that the ongoing effort has done an excellent job of sampling the most abundant organisms but struggles to sample the rarer organisms. Through the use of new sequencing technologies, we should be able to obtain full-length sequences from these rare organisms. Furthermore, we suggest that by allocating more resources to sampling environments known to have the greatest biodiversity, we will be able to make significant advances in our characterization of archaeal and bacterial diversity. PMID- 27190215 TI - Ubiquitin-Like Proteasome System Represents a Eukaryotic-Like Pathway for Targeted Proteolysis in Archaea. AB - The molecular mechanisms of targeted proteolysis in archaea are poorly understood, yet they may have deep evolutionary roots shared with the ubiquitin proteasome system of eukaryotic cells. Here, we demonstrate in archaea that TBP2, a TATA-binding protein (TBP) modified by ubiquitin-like isopeptide bonds, is phosphorylated and targeted for degradation by proteasomes. Rapid turnover of TBP2 required the functions of UbaA (the E1/MoeB/ThiF homolog of archaea), AAA ATPases (Cdc48/p97 and Rpt types), a type 2 JAB1/MPN/MOV34 metalloenzyme (JAMM/MPN+) homolog (JAMM2), and 20S proteasomes. The ubiquitin-like protein modifier small archaeal modifier protein 2 (SAMP2) stimulated the degradation of TBP2, but SAMP2 itself was not degraded. Analysis of the TBP2 fractions that were not modified by ubiquitin-like linkages revealed that TBP2 had multiple N termini, including Met1-Ser2, Ser2, and Met1-Ser2(p) [where (p) represents phosphorylation]. The evidence suggested that the Met1-Ser2(p) form accumulated in cells that were unable to degrade TBP2. We propose a model in archaea in which the attachment of ubiquitin-like tags can target proteins for degradation by proteasomes and be controlled by N-terminal degrons. In support of a proteolytic mechanism that is energy dependent and recycles the ubiquitin-like protein tags, we find that a network of AAA ATPases and a JAMM/MPN+ metalloprotease are required, in addition to 20S proteasomes, for controlled intracellular proteolysis. IMPORTANCE: This study advances the fundamental knowledge of signal guided proteolysis in archaea and sheds light on components that are related to the ubiquitin-proteasome system of eukaryotes. In archaea, the ubiquitin-like proteasome system is found to require function of an E1/MoeB/ThiF homolog, a type 2 JAMM/MPN+ metalloprotease, and a network of AAA ATPases for the targeted destruction of proteins. We provide evidence that the attachment of the ubiquitin like protein is controlled by an N-terminal degron and stimulates proteasome mediated proteolysis. PMID- 27190216 TI - Loss of Dependence on Continued Expression of the Human Papillomavirus 16 E7 Oncogene in Cervical Cancers and Precancerous Lesions Arising in Fanconi Anemia Pathway-Deficient Mice. AB - Fanconi anemia (FA) is a rare genetic disorder caused by defects in DNA damage repair. FA patients often develop squamous cell carcinoma (SCC) at sites where high-risk human papillomaviruses (HPVs) are known to cause cancer, including the cervix. However, SCCs found in human FA patients are often HPV negative, even though the majority of female FA patients with anogenital cancers had preexisting HPV-positive dysplasia. We hypothesize that HPVs contribute to the development of SCCs in FA patients but that the continued expression of HPV oncogenes is not required for the maintenance of the cancer state because FA deficiency leads to an accumulation of mutations in cellular genes that render the cancer no longer dependent upon viral oncogenes. We tested this hypothesis, making use of Bi-L E7 transgenic mice in which we temporally controlled expression of HPV16 E7, the dominant viral oncogene in HPV-associated cancers. As seen before, the persistence of cervical neoplastic disease was highly dependent upon the continued expression of HPV16 E7 in FA-sufficient mice. However, in mice with FA deficiency, cervical cancers persisted in a large fraction of the mice after HPV16 E7 expression was turned off, indicating that these cancers had escaped from their dependency on E7. Furthermore, the severity of precancerous lesions also failed to be reduced significantly in the mice with FA deficiency upon turning off expression of E7. These findings confirm our hypothesis and may explain the fact that, while FA patients have a high frequency of infections by HPVs and HPV-induced precancerous lesions, the cancers are frequently HPV negative. IMPORTANCE : Fanconi anemia (FA) patients are at high risk for developing squamous cell carcinoma (SCC) at sites where high-risk human papillomaviruses (HPVs) frequently cause cancer. Yet these SCCs are often HPV negative. FA patients have a genetic defect in their capacity to repair damaged DNA. HPV oncogenes cause an accumulation of DNA damage. We hypothesize, therefore, that DNA damage induced by HPV leads to an accumulation of mutations in patients with FA deficiency and that such mutations allow HPV-driven cancers to become independent of the viral oncogenes. Consistent with this hypothesis, we found that cervical cancers arising in HPV16 transgenic mice with FA deficiency frequently escape from dependency on the HPV16 oncogene that drove its development. Our report provides further support for vaccination of FA patients against HPVs and argues for the need to define mutational profiles of SCCs arising in FA patients in order to inform precision medicine-based approaches to treating these patients. PMID- 27190218 TI - Type I Interferons in Newborns-Neurotoxicity versus Antiviral Defense. AB - In most children and adults, primary infection with herpes simplex virus 1 (HSV 1) is asymptomatic. However, very rarely (incidence of 1 in 1,000,000), it can cause herpes simplex encephalitis (HSE). HSE also occurs in infants but with a much starker incidence of one in three. This age difference in susceptibility to HSV-1-caused HSE is not well understood. In a recent article in mBio, authors have identified the choroid plexus as the anatomical site of robust HSV-1 replication in the brain. They point to low levels of type I interferon (IFN) receptor as causal of the lack of HSV-1 replication control in neonates, in contrast to adults. Here, I discuss these findings in the context of human genetic evidence. I point to the balancing act of type I IFN acting as a neurotoxin and an antiviral agent, an evolutionary choice of a lesser evil. PMID- 27190217 TI - A Herpesviral Lytic Protein Regulates the Structure of Latent Viral Chromatin. AB - Latent infections by viruses usually involve minimizing viral protein expression so that the host immune system cannot recognize the infected cell through the viral peptides presented on its cell surface. Herpes simplex virus (HSV), for example, is thought to express noncoding RNAs such as latency-associated transcripts (LATs) and microRNAs (miRNAs) as the only abundant viral gene products during latent infection. Here we describe analysis of HSV-1 mutant viruses, providing strong genetic evidence that HSV-infected cell protein 0 (ICP0) is expressed during establishment and/or maintenance of latent infection in murine sensory neurons in vivo Studies of an ICP0 nonsense mutant virus showed that ICP0 promotes heterochromatin and latent and lytic transcription, arguing that ICP0 is expressed and functional. We propose that ICP0 promotes transcription of LATs during establishment or maintenance of HSV latent infection, much as it promotes lytic gene transcription. This report introduces the new concept that a lytic viral protein can be expressed during latent infection and can serve dual roles to regulate viral chromatin to optimize latent infection in addition to its role in epigenetic regulation during lytic infection. An additional implication of the results is that ICP0 might serve as a target for an antiviral therapeutic acting on lytic and latent infections. IMPORTANCE: Latent infection by viruses usually involves minimizing viral protein synthesis so that the host immune system cannot recognize the infected cells and eliminate them. Herpes simplex virus has been thought to express only noncoding RNAs as abundant gene products during latency. In this study, we found genetic evidence that an HSV lytic protein is functional during latent infection, and this protein may provide a new target for antivirals that target both lytic and latent infections. PMID- 27190220 TI - Erratum for Fang and Casadevall, Research Funding: the Case for a Modified Lottery. PMID- 27190219 TI - One More Disguise in the Stealth Behavior of Streptococcus pyogenes. AB - The ability to hide in the animal kingdom is essential for survival; the same is true for bacteria. Streptococcus pyogenes is considered one of the more successful stealth bacteria in its production of a hyaluronic acid capsule that is chemically identical to the hyaluronic acid lining human joints. It has also acquired the capacity to enter eukaryotic cells to avoid the onslaught of the host's immune defenses, as well as drugs. From this intracellular vantage point, it may remain dormant from days to weeks, only to cause disease again at a later time, perhaps causing a relapse in a drug-treated patient. We now learn that it is able to enter macrophages as well, enabling the Streptococcus to use this "Trojan horse" approach to be transported to distant sites in the body. PMID- 27190221 TI - Correction to: "Biased Type 1 Cannabinoid Receptor Signaling Influences Neuronal Viability in a Cell Culture Model of Huntington Disease". PMID- 27190223 TI - A review of CARE's Community Score Card experience and evidence. AB - The global community's growing enthusiasm for the potential of social accountability approaches to improve health system performance and accelerate health progress makes it imperative that we learn from social accountability intervention implementation experience and results. To this end, we carried out a review of Cooperative for Assistance and Relief Everywhere, Inc. (CARE)'s experience with the Community Score Card(c) (CSC)-a social accountability approach CARE developed in Malawi. We reviewed projects that CARE implemented between 2002 and 2013 that employed the CSC and that had at least one evaluation in English. We systematically collected and synthesized information from evaluations on the projects' characteristics, CSC-related outcomes and challenges. Eight projects, spanning five countries, met our inclusion criteria. The projects applied the CSC to various focus areas, mostly health. We identified one to three evaluations, mostly qualitative, for each project. While the evaluations had many limitations, consistency of the results, as well as the range of outcomes, suggests that the CSC is contributing to significant changes. All projects reported CSC-related governance outcomes and service outcomes. There is promising evidence that the CSC can contribute to citizen empowerment, service provider and power-holder effectiveness, accountability and responsiveness and spaces for negotiation between the two that are expanded, effective and inclusive. There is also evidence that the CSC may contribute to improvements in service availability, access, utilization and quality. The CSC seems particularly suited to building trust and strengthening relationships between the community and service providers and to improving the user-centred dimension of quality. All of the projects reported challenges, with ensuring national responsiveness and inclusion of marginalized groups in the CSC process proving to be the most intractable. To improve health system performance and accelerate health progress we recommend further CSC use, enhancements and research. PMID- 27190224 TI - Effect of High-Frequency Oscillations on Cough Peak Flows Generated by Mechanical In-Exsufflation in Medically Stable Subjects With Amyotrophic Lateral Sclerosis. AB - BACKGROUND: Mechanically assisted coughing with mechanical in-exsufflation (MI-E) is recommended for noninvasive management of respiratory secretions in amyotrophic lateral sclerosis (ALS). To improve the effectiveness of the technique, a new device combining MI-E with high-frequency oscillations (HFO) has been developed. This work aimed to assess the effect of HFO on the cough peak flow generated by MI-E in medically stable subjects with ALS. METHODS: This was a prospective study that included subjects with ALS in a medically stable condition. Cough peak flow generated by MI-E was measured in 4 situations: without HFO, with HFO during insufflation, with HFO during exsufflation, and with HFO in both cycles. The parameters used were: insufflation pressure of +40 cm H2O, exsufflation pressure of -40 cm H2O, insufflation time 2 s, exsufflation time 3 s, amplitude of oscillations 10 cm H2O, and frequency of oscillations 15 Hz. RESULTS: Forty-seven subjects with ALS were included: 66% males, 68.2 +/- 9.2 y, 40% with bulbar onset, FVC = 1.7 +/- 1.1 L, percent-of-predicted FVC = 54.4 +/ 26.6%, cough peak flow = 3.8 +/- 2.2 L/s, PImax = -39.4 +/- 26.4 cm H2O, revised ALS scale = 28.5 +/- 9.3, Norris bulbar subscore = 26.1 +/- 10.4. No statistical differences were found in cough peak flow generated by MI-E in the 4 situations (without HFO = 4.0 +/- 1.2 L/s, with insufflation HFO = 3.9 +/- 1.2 L/s, with exsufflation HFO = 4.1 +/- 1.2 L/s, with in-exsufflation HFO = 3.9 +/- 1.1 L/s). CONCLUSIONS: The addition of HFO to mechanically assisted coughing with MI-E does not have an effect on the cough peak flow of medically stable subjects with ALS. PMID- 27190222 TI - Effectiveness of interventions to provide culturally appropriate maternity care in increasing uptake of skilled maternity care: a systematic review. AB - Addressing cultural factors that affect uptake of skilled maternity care is recognized as an important step in improving maternal and newborn health. This article describes a systematic review to examine the evidence available on the effects of interventions to provide culturally appropriate maternity care on the use of skilled maternity care during pregnancy, for birth or in the postpartum period. Items published in English, French and/or Spanish between 1 January 1990 and 31 March 2014 were considered. Fifteen studies describing a range of interventions met the inclusion criteria. Data were extracted on population and intervention characteristics; study design; definitions and data for relevant outcomes; and the contexts and conditions in which interventions occurred. Because most of the included studies focus on antenatal care outcomes, evidence of impact is particularly limited for care seeking for birth and after birth. Evidence in this review is clustered within a small number of countries, and evidence from low- and middle-income countries is notably lacking. Interventions largely had positive effects on uptake of skilled maternity care. Cultural factors are often not the sole factor affecting populations' use of maternity care services. Broader social, economic, geographical and political factors interacted with cultural factors to affect targeted populations' access to services in included studies. Programmes and policies should seek to establish an enabling environment and support respectful dialogue with communities to improve use of skilled maternity care. Whilst issues of culture are being recognized by programmes and researchers as being important, interventions that explicitly incorporate issues of culture are rarely evaluated. PMID- 27190225 TI - Benefits of walking and solo experiences in UK wild places. AB - This paper examines human-nature interaction and how therapeutic this relationship is by investigating the efficacy of structured outdoor experience. Two walking and solo experience (WSEs) explored university students' (aged 20-43 years) perceptions of walking through and being with nature. The first was a 5 day journey (n = 4; 3 females and 1 male) and the second (n = 5; 3 females and 2 males) took place over two weekends, with a 2-week interval in-between. Pre- and post-experience interviews, journal writing, group discussions and a 9-month follow-up interviews were used to collect data and thematic analysis [Braun and Clarke (Using thematic analysis in psychology. Qual Res Psychol 2006;3:77-101.)] was applied. Both WSEs were considered together during analysis, as well as comparisons made between the two, in order to evaluate implications for practice. Benefits of the WSE that contributed to a general sense of well-being were: (i) gaining a sense of freedom and escape; (ii) gaining a sense of awareness and sensitivity to one's environment and its influence (iii) gaining confidence in being able to cope and take action; (iv) gaining a sense of perspective on and appreciation for life. Furthermore, the meaning participants formed in relation to their environment before, during and after the WSE, and the activity within that environment, played a role in their sense of well-being and in their motivations to re-access nature in other places. Findings suggest that WSEs are a cost effective way to give rise to beneficial and durable experiences, but a more holistic approach to policy is needed. PMID- 27190226 TI - Comment on: Real-life effectiveness of canakinumab in cryoprin-associated periodic syndrome. PMID- 27190227 TI - Golf: a matter of life and death, health and happiness, or just Olympic medals? PMID- 27190228 TI - Rugby Sevens: Olympic debutante and research catalyst. PMID- 27190229 TI - Injury and illness surveillance at the International Sailing Federation Sailing World Championships 2014. AB - BACKGROUND/AIM: The Sailing World Championships 2014 was contested by 1167 sailors in all 10 Olympic classes. Our objective was to characterise sailing related injuries and illnesses in sailors participating in this regatta. METHODS: We conducted 2 surveys: (1) prior to the World Championships, sailors answered a 12-month recall questionnaire on sailing-related injuries and illnesses and (2) during the Championships, injuries and illnesses were documented. RESULTS: There were 760 respondents (65% of all participants) for the 12-month recall questionnaire (58% male, 42% female), of whom 244 participants reported 299 injuries (0.59 injuries per 1000 h of sailing). Injuries were most prevalent in the 49erFX (64%), RS:X Women (39%), 49er (37%) and Nacra 17 (36%). Lower back (29% of sailors), knee (13%), shoulder (12%) and ankle (10%) injuries were most prevalent; most (58% of all injuries) were overuse injuries; and 56% of sailors lost sailing time. Most illnesses (40%) were infections, primarily of the respiratory system (43%). During the Championships, there were 67 injuries (4 per 1000 days of sailing). The 49er (24% of all injuries), 470 Men and Women (24%), and 49erFX (19%) had the highest incidence. Injuries to the hand/fingers (22% of all injuries), back (18%), and foot (12%) were most common, as were contusions (37% of all injuries), cuts/lacerations (24%), and sprains (9%). Of the 29 illnesses (2 per 1000 days of sailing), 9 (31%) were gastrointestinal and 6 (21%) respiratory, while 2 (7%) were gout attacks. CONCLUSIONS: The Olympic classes introduced since 2000 (49erFX, 49er, Nacra 17) have resulted in a rise in injuries. PMID- 27190230 TI - Should player fatigue be the focus of injury prevention strategies for international rugby sevens tournaments? AB - OBJECTIVE: To assess the incidence, severity and nature of injuries, to determine risk factors for injury and to identify potential injury prevention strategies in men's international Rugby-7s tournaments. DESIGN: A prospective cohort study. PARTICIPANTS: Players from core teams competing in matches at 6 Sevens World Series from 2008/2009 to 2014/2015. RESULTS: The incidence of injury across all Series was 108.3 injuries/1000 player-match-hours (backs: 121.0; forwards: 91.5) with a mean severity of 44.2 days (backs: 46.1; forwards: 40.9) and a median severity of 28 days (backs: 29; forwards: 26). The proportion of injuries sustained in the second half was significantly higher (60%; p<0.001) than the first half of matches and the proportion increased from match to match and day to day in a tournament. The knee (17.4%), ankle (15.9%) and posterior thigh (13.2%) were the most common injury locations for backs and the knee (18.5%), head/face (17.3%) and shoulder/clavicle (13.0%) for forwards. The four most common injuries across all players were knee ligament (13.0%), ankle ligament (12.8%), concussion (10.4%) and posterior thigh muscle strains (9.8%). CONCLUSIONS: The incidence of injury in Rugby-7s suggests that teams require squads of around 20 players for a Sevens World Series. The higher incidence of injury in the second half of matches is probably the result of player fatigue; therefore, injury prevention strategies for teams and the Governing Body should address this issue. The results presented support the World Rugby trial allowing 'rolling substitutes' during Sevens World Series matches, as this approach may help to mitigate the effects of player fatigue during the second half of matches. PMID- 27190231 TI - A systematic computational analysis of the rRNA-3' UTR sequence complementarity suggests a regulatory mechanism influencing post-termination events in metazoan translation. AB - Nucleic acid sequence complementarity underlies many fundamental biological processes. Although first noticed a long time ago, sequence complementarity between mRNAs and ribosomal RNAs still lacks a meaningful biological interpretation. Here we used statistical analysis of large-scale sequence data sets and high-throughput computing to explore complementarity between 18S and 28S rRNAs and mRNA 3' UTR sequences. By the analysis of 27,646 full-length 3' UTR sequences from 14 species covering both protozoans and metazoans, we show that the computed 18S rRNA complementarity creates an evolutionarily conserved localization pattern centered around the ribosomal mRNA entry channel, suggesting its biological relevance and functionality. Based on this specific pattern and earlier data showing that post-termination 80S ribosomes are not stably anchored at the stop codon and can migrate in both directions to codons that are cognate to the P-site deacylated tRNA, we propose that the 18S rRNA-mRNA complementarity selectively stabilizes post-termination ribosomal complexes to facilitate ribosome recycling. We thus demonstrate that the complementarity between 18S rRNA and 3' UTRs has a non-random nature and very likely carries information with a regulatory potential for translational control. PMID- 27190232 TI - Characterization of CRISPR RNA transcription by exploiting stranded metatranscriptomic data. AB - CRISPR-Cas systems are bacterial adaptive immune systems, each typically composed of a locus of cas genes and a CRISPR array of spacers flanked by repeats. Processed transcripts of CRISPR arrays (crRNAs) play important roles in the interference process mediated by these systems, guiding targeted immunity. Here we developed computational approaches that allow us to characterize the expression of many CRISPRs in their natural environments, using community RNA-seq (metatranscriptomic) data. By exploiting public human gut metatranscriptomic data sets, we studied the expression of 56 repeat-sequence types of CRISPRs, revealing that most CRISPRs are transcribed in one direction (producing crRNAs). In rarer cases, including a type II system associated with Bacteroides fragilis, CRISPRs are transcribed in both directions. Type III CRISPR-Cas systems were found in the microbiomes, but metatranscriptomic reads were barely found for their CRISPRs. We observed individual-level variation of the crRNA transcription, and an even greater transcription of a CRISPR from the antisense strand than the crRNA strand in one sample. The orientations of CRISPR expression implicated by metatranscriptomic data are largely in agreement with prior predictions for CRISPRs, with exceptions. Our study shows the promise of exploiting community RNA seq data for investigating the transcription of CRISPR-Cas systems. PMID- 27190233 TI - LDSS-P: an advanced algorithm to extract functional short motifs associated with coordinated gene expression. AB - Identifying functional elements in promoter sequences is a major goal in computational and experimental genome biology. Here, we describe an algorithm, Local Distribution of Short Sequences for Prokaryotes (LDSS-P), to identify conserved short motifs located at specific positions in the promoters of co expressed prokaryotic genes. As a test case, we applied this algorithm to a symbiotic nitrogen-fixing bacterium, Sinorhizobium meliloti The LDSS-P profiles that overlap with the 5' section of the extracytoplasmic function RNA polymerase sigma factor RpoE2 consensus sequences displayed a sharp peak between -34 and -32 from TSS positions. The corresponding genes overlap significantly with RpoE2 targets identified from previous experiments. We further identified several groups of genes that are co-regulated with characterized marker genes. Our data indicate that in S. meliloti, and possibly in other Rhizobiaceae species, the master cell cycle regulator CtrA may recognize an expanded motif (AACCAT), which is positionally shifted from the previously reported CtrA consensus sequence in Caulobacter crescentus Bacterial one-hybrid experiments showed that base substitution in the expanded motif either increase or decrease the binding by CtrA. These results show the effectiveness of LDSS-P as a method to delineate functional promoter elements. PMID- 27190235 TI - Differential distribution improves gene selection stability and has competitive classification performance for patient survival. AB - A consistent difference in average expression level, often referred to as differential expression (DE), has long been used to identify genes useful for classification. However, recent cancer studies have shown that when transcription factors or epigenetic signals become deregulated, a change in expression variability (DV) of target genes is frequently observed. This suggests that assessing the importance of genes by either differential expression or variability alone potentially misses sets of important biomarkers that could lead to improved predictions and treatments. Here, we describe a new approach for assessing the importance of genes based on differential distribution (DD), which combines information from differential expression and differential variability into a unified metric. We show that feature ranking and selection stability based on DD can perform two to three times better than DE or DV alone, and that DD yields equivalent error rates to DE and DV. Finally, assessing genes via differential distribution produces a complementary set of selected genes to DE and DV, potentially opening up new categories of biomarkers. PMID- 27190234 TI - RNAontheBENCH: computational and empirical resources for benchmarking RNAseq quantification and differential expression methods. AB - RNA sequencing (RNAseq) has become the method of choice for transcriptome analysis, yet no consensus exists as to the most appropriate pipeline for its analysis, with current benchmarks suffering important limitations. Here, we address these challenges through a rich benchmarking resource harnessing (i) two RNAseq datasets including ERCC ExFold spike-ins; (ii) Nanostring measurements of a panel of 150 genes on the same samples; (iii) a set of internal, genetically determined controls; (iv) a reanalysis of the SEQC dataset; and (v) a focus on relative quantification (i.e. across-samples). We use this resource to compare different approaches to each step of RNAseq analysis, from alignment to differential expression testing. We show that methods providing the best absolute quantification do not necessarily provide good relative quantification across samples, that count-based methods are superior for gene-level relative quantification, and that the new generation of pseudo-alignment-based software performs as well as established methods, at a fraction of the computing time. We also assess the impact of library type and size on quantification and differential expression analysis. Finally, we have created a R package and a web platform to enable the simple and streamlined application of this resource to the benchmarking of future methods. PMID- 27190238 TI - Hans Georg Truper (1936-2016). PMID- 27190237 TI - Antigenic characterization of dimorphic surface protein in Mycobacterium tuberculosis. AB - The Mycobacterium tuberculosis Rv0679c protein is a surface protein that contributes to host cell invasion. We previously showed that a single nucleotide transition of the Rv0679c gene leads to a single amino acid substitution from asparagine to lysine at codon 142 in the Beijing genotype family. In this study, we examined the immunological effect of this substitution. Several recombinant proteins were expressed in Escherichia coli and Mycobacterium smegmatis and characterized with antisera and two monoclonal antibodies named 5D4-C2 and 8G10 H2. A significant reduction of antibody binding was detected by enzyme-linked immunosorbent assay (ELISA) and western blot analysis in the Lys142-type protein. This reduction of 8G10-H2 binding was more significant, with the disappearance of a signal in the proteins expressed by recombinant mycobacteria in western blot analysis. In addition, epitope mapping analysis of the recombinant proteins showed a linear epitope by 5D4-C2 and a discontinuous epitope by 8G10-H2. The antibody recognizing the conformational epitope detected only mycobacterial Asn142-type recombinant protein. Our results suggest that a single amino acid substitution of Rv0679c has potency for antigenic change in Beijing genotype strains. PMID- 27190236 TI - Heatmapper: web-enabled heat mapping for all. AB - Heatmapper is a freely available web server that allows users to interactively visualize their data in the form of heat maps through an easy-to-use graphical interface. Unlike existing non-commercial heat map packages, which either lack graphical interfaces or are specialized for only one or two kinds of heat maps, Heatmapper is a versatile tool that allows users to easily create a wide variety of heat maps for many different data types and applications. More specifically, Heatmapper allows users to generate, cluster and visualize: (i) expression-based heat maps from transcriptomic, proteomic and metabolomic experiments; (ii) pairwise distance maps; (iii) correlation maps; (iv) image overlay heat maps; (v) latitude and longitude heat maps and (vi) geopolitical (choropleth) heat maps. Heatmapper offers a number of simple and intuitive customization options for facile adjustments to each heat map's appearance and plotting parameters. Heatmapper also allows users to interactively explore their numeric data values by hovering their cursor over each heat map cell, or by using a searchable/sortable data table view. Heat map data can be easily uploaded to Heatmapper in text, Excel or tab delimited formatted tables and the resulting heat map images can be easily downloaded in common formats including PNG, JPG and PDF. Heatmapper is designed to appeal to a wide range of users, including molecular biologists, structural biologists, microbiologists, epidemiologists, environmental scientists, agriculture/forestry scientists, fish and wildlife biologists, climatologists, geologists, educators and students. Heatmapper is available at http://www.heatmapper.ca. PMID- 27190239 TI - Watch out for your TRP1 marker: the effect of TRP1 gene on the growth at high and low temperatures in budding yeast. AB - TRP1 is a frequently used auxotrophic marker for genetic modifications and selections in trp(-) budding yeast strains, including the commonly used wild-type strain W303a. However, we found that introduction of the TRP1 gene into a trp(-) strain significantly affected vegetative growth at low and high temperatures. Therefore, caution should be needed when working in a trp(-) background strain and using the TRP1 marker to study stress response phenotypes, particularly when analyzing temperature sensitivities. PMID- 27190240 TI - Accumulation of PHA granules in Cupriavidus necator as seen by confocal fluorescence microscopy. AB - Many bacteria are capable of accumulating intracellular granules of polyhydroxyalkanoates (PHA). In this work, we developed confocal microscopy analysis of bacterial cells to study changes in the diameters of cells as well as PHA granules during growth and PHA accumulation in the bacterium Cupriavidus necator H16 (formerly Ralstonia eutropha). The cell envelope was stained by DiD((r)) fluorescent probe and PHA granules by Nile Red. Signals from both probes were separated based on their spectral and fluorescence life-time properties. During growth and PHA accumulation, bacterial cells increased their length but the width of the cells remained constant. The volume fraction of PHA granules in cells increased during PHA accumulation, nevertheless, its value did not exceed 40 vol. % regardless of the PHA weight content. It seems that bacterial cultures lengthen the cells in order to control the PHA volume portion. However, since similar changes in cell length were also observed in a PHA non-accumulating mutant, it seems that there is no direct control mechanism, which regulates the prolongation of the cells with respect to PHA granules volume. It is more likely that PHA biosynthesis and the length of cells are influenced by the same external stimuli such as nutrient limitation. PMID- 27190241 TI - Diversity and distribution of catechol 2, 3-dioxygenase genes in surface sediments of the Bohai Sea. AB - Catechol 2, 3-dioxygenase (C23O) is the key enzyme for aerobic aromatic degradation. Based on clone libraries and quantitative real-time polymerase chain reaction, we characterized diversity and distribution patterns of C23O genes in surface sediments of the Bohai Sea. The results showed that sediments of the Bohai Sea were dominated by genes related to C23O subfamily I.2.A. The samples from wastewater discharge area (DG) and aquaculture farm (KL) showed distinct composition of C23O genes when compared to the samples from Bohai Bay (BH), and total organic carbon was a crucial determinant accounted for the composition variation. C6BH12-38 and C2BH2-35 displayed the highest gene copies and highest ratios to the 16S rRNA genes in KL, and they might prefer biologically labile aromatic hydrocarbons via aquaculture inputs. Meanwhile, C7BH3-48 showed the highest gene copies and highest ratios to the 16S rRNA genes in DG, and this could be selective effect of organic loadings from wastewater discharge. An evident increase in C6BH12-38 and C7BH3-48 gene copies and reduction in diversity of C23O genes in DG and KL indicated composition perturbations of C23O genes and potential loss in functional redundancy. We suggest that ecological habitat and trophic specificity could shape the distribution of C23O genes in the Bohai Sea sediments. PMID- 27190242 TI - False detection of Coxiella burnetii-what is the risk? PMID- 27190243 TI - ATF3 provides protection from Staphylococcus aureus and Listeria monocytogenes infections. PMID- 27190244 TI - Colony types and virulence traits of Legionella feeleii determined by exopolysaccharide materials. AB - Legionella feeleii is a Gram-negative pathogenic bacterium that causes Pontiac fever and pneumonia in humans. When L. feeleii serogroup 1 (ATCC 35072) was cultured on BCYE agar plates, two types of colonies were observed and exhibited differences in color, opacity and morphology. Since the two colony types are white rugose and brown translucent, they were termed as white rugose L. feeleii (WRLf) and brown translucent L. feeleii (BTLf), respectively. They exhibited different growth capacities in BYE broth in vitro, and it was found that WRLf could transform to BTLf. Under the electron microscope, it was observed that WRLf secreted materials which could be stained with ruthenium red, which was absent in BTLf. When U937 macrophages and HeLa cells were infected with the bacteria, WRLf manifested stronger internalization ability than BTLf. Intracellular growth in murine macrophages and Acanthamoeba cells was affected by the level of initial phagocytosis. WRLf was more resistant to human serum bactericidal action than BTLf. After being inoculated to guinea pigs, both organisms caused fever in the animals. These results suggest that ruthenium red-stained materials secreted in the surroundings may play a crucial role in determining L. feeleii colony morphology and virulence traits. PMID- 27190245 TI - Programmable biomaterials for dynamic and responsive drug delivery. AB - Biomaterials are continually being designed that enable new methods for interacting dynamically with cell and tissues, in turn unlocking new capabilities in areas ranging from drug delivery to regenerative medicine. In this review, we explore some of the recent advances being made in regards to programming biomaterials for improved drug delivery, with a focus on cancer and infection. We begin by explaining several of the underlying concepts that are being used to design this new wave of drug delivery vehicles, followed by examining recent materials systems that are able to coordinate the temporal delivery of multiple therapeutics, dynamically respond to changing tissue environments, and reprogram their bioactivity over time. PMID- 27190246 TI - Original Research: Metabolic alterations from early life thyroxine replacement therapy in male Ames dwarf mice are transient. AB - Ames dwarf mice are exceptionally long-lived due to a Prop1 loss of function mutation resulting in deficiency of growth hormone, thyroid-stimulating hormone and prolactin. Deficiency in thyroid-stimulating hormone and growth hormone leads to greatly reduced levels of circulating thyroid hormones and insulin-like growth factor 1, as well as a reduction in insulin secretion. Early life growth hormone replacement therapy in Ames dwarf mice significantly shortens their longevity, while early life thyroxine (T4) replacement therapy does not. Possible mechanisms by which early life growth hormone replacement therapy shortens longevity include deleterious effects on glucose homeostasis and energy metabolism, which are long lasting. A mechanism explaining why early life T4 replacement therapy does not shorten longevity remains elusive. Here, we look for a possible explanation as to why early life T4 replacement therapy does not impact longevity of Ames dwarf mice. We found that early life T4 replacement therapy increased body weight and advanced the age of sexual maturation. We also find that early life T4 replacement therapy does not impact glucose tolerance or insulin sensitivity, and any deleterious effects on oxygen consumption, respiratory quotient and heat production are transient. Lastly, we find that early life T4 replacement therapy has long-lasting effects on bone mineral density and bone mineral content. We suggest that the transient effects on energy metabolism and lack of effects on glucose homeostasis are the reasons why there is no shortening of longevity after early life T4 replacement therapy in Ames dwarf mice. PMID- 27190247 TI - Development of a bead-based suspension array for the detection of pathogens in acute respiratory tract infections. AB - We developed a high-throughput bead-based suspension array for simultaneous detection of 20 respiratory tract pathogens in clinical specimens. Pathogen specific genes were amplified and hybridized to probes coupled to carboxyl encoded microspheres. Fluorescence intensities generated via the binding of phycoerythrin-conjugated streptavidin with biotin-labeled targets were measured by the Luminex 100 bead-based suspension array system. The bead-based suspension array detected bacteria in a significantly higher number of samples compared to the conventional culture. There was no significant difference in the detection rate of atypical pathogensatypical pathogens or viruses between the bead-based suspension array and real-time PCR. This technology can play a significant role in screening patients with pneumonia. PMID- 27190248 TI - Original Research: Influence of okadaic acid on hyperphosphorylation of tau and nicotinic acetylcholine receptors in primary neurons. AB - The aim of the study was to investigate the influence of hyperphosphorylation of tau induced by okadaic acid on the expression of nicotinic acetylcholine receptors and the neurotoxicity of beta-amyloid peptide. Primary cultures of neurons isolated from the hippocampus of the brains of neonatal rats were exposed to okadaic acid or/and Abeta1-42 Tau phosphorylated at Ser404 and Ser202, and the protein expressions of alpha7, alpha4 and alpha3 nAChR subunits were quantified by Western blotting, and their corresponding mRNAs by real-time PCR. Superoxide dismutase activity was assayed biochemically and malondialdehyde by thiobarbituric acid-reactive substance. As compared to controls, phosphorylations of tau at Ser404 and Ser202 in the neurons were elevated by exposure to 20 nM okadaic acid for 48 h but not by 1 or 2 uM Abeta1-42 Treatment with 20 nM okadaic acid or 1 uM Abeta1-42 for 48 h resulted in the reduced alpha7, alpha4 and alpha3 proteins, and alpha4 and alpha3 mRNAs, as well as the decreased activity of superoxide dismutase and the increased malondialdehyde. Okadaic acid and Abeta1 42 together caused more pronounced changes in the expressions of alpha7 and alpha4, superoxide dismutase activity and lipid peroxidation than either alone. When pre-treatment with vitamin E or lovastatin, the neurotoxicity induced by okadaic acid was significantly attenuated. These findings indicate that hyperphosphorylation of tau induced by okadaic acid inhibits the expression of nicotinic acetylcholine receptors at both the protein and mRNA levels, as well as enhances the neurotoxicity of beta-amyloid peptide. PMID- 27190249 TI - Gradually increased oxygen administration promoted survival after hemorrhagic shock. AB - Gradually increased oxygen administration (GIOA) seems promising in hemorrhagic shock. However, the effects of GIOA on survival remain unclear, and details of GIOA are to be identified. After the induction of hemorrhagic shock, the rats were randomized into five groups (n = 9): normoxic group (Normo), hyperoxic group (Hypero), normoxic to hyperoxic group (GIOA1), long-time hypoxemic to hyperoxic group (GIOA2), and short-time hypoxemic to hyperoxic group (GIOA3). Survival was recorded for 96 h, plasma alanine transaminase, oxidative stress, hemodynamics, and blood gas were measured. The mean survival time of the GIOA3 was significantly longer than that of the Normo, Hypero, and GIOA2. Plasma alanine transaminase levels were significantly lower in the Normo, GIOA1, and GIOA3 compared to the Hypero and GIOA2 at 2 h post-resuscitation (PR). Plasma 3 nitrotyrosine levels at 2 h PR were significantly lower in the GIOA2 and GIOA3 compared to the Normo and Hypero. Central venous oxygen saturation at 2 h PR in the GIOA3 was significantly higher than the Normo; however, no significant difference was observed between GIOA1 and Normo. Besides, at 2 h PR, mean arterial pressure in the GIOA3 was significantly higher than the GIOA2; however, no significant difference was observed between GIOA1 and GIOA2. (1) GIOA could significantly prolong survival time compared to normoxemic resuscitation and hyperoxic resuscitation; (2) early moments of GIOA are critical to the benefits; and (3) hypoxemia at onset of resuscitation may be imperative, more works are needed to determine the optimal initial oxygen concentration of GIOA. PMID- 27190250 TI - Exogenous spermine inhibits hypoxia/ischemia-induced myocardial apoptosis via regulation of mitochondrial permeability transition pore and associated pathways. AB - Myocardial infarction (MI) is associated with a high mortality rate, which is attributed to the effects of myocyte loss that occurs as a result of ischemia induced cell death. Very few therapies can effectively prevent or delay the effects of ischemia. Polyamines (PAs) are polycations required for cell growth and division, and their use may prevent cell loss. The aim of this study was to investigate the relationship between hypoxia/ischemia (H/I)-induced cell apoptosis and PA metabolism and to investigate the ability of spermine to limit H/I injury in cardiomyocytes by blocking the mitochondrial apoptotic pathway. Neonatal rat cardiomyocytes were placed under hypoxic conditions for 24 h after being subjected to 5 MUM of spermine as a pretreatment therapy. H/I induced PA catabolism, which was indicated by a 1.3-fold up-regulation of spermidine/spermine N(1)-acetyltransferase expression. Exogenous spermine significantly reduced H/I-induced cell death rate (60 +/- 2 to 36 +/- 2%) and apoptosis rate (42 +/- 2 to 21 +/- 2%); it also attenuated lactate dehyodrogenase and creatine kinase leakage (440 +/- 13 and 336 +/- 16 U/L to 275 +/- 15 and 235 +/- 13 U/L). Furthermore, it decreases calcium overload (3.8 +/- 0.2 to 2.2 +/- 0.1 a.u.). Moreover, spermine pretreatment remarkably decreased cytochrome c release from the mitochondria to the cytosol, lowering the expression of cleaved caspase-3 and -9. With spermine pretreatment, there was an increase in Bcl-2 levels and phosphorylation of ERK1/2, phosphoinositide 3-kinase, Akt, and GSK 3beta, preserving mitochondrial membrane potential and inducing an mitochondrial permeability transition pore opening. In conclusion, H/I decreased endogenous spermine concentrations in cardiomyocytes, which ultimately induced apoptosis. The addition of exogenous spermine effectively prevented myocyte cell death. PMID- 27190251 TI - Original Research: Polyphenols extracted from grape powder induce lipogenesis and glucose uptake during differentiation of murine preadipocytes. AB - Assessing the effects of grapes and grape powder extracted polyphenols on lipogenesis and glucose uptake in adipocytes may clarify the risk/benefit of recommending them to individuals with obesity and insulin resistance. We investigated the effect of grape powder extracted polyphenols (GPEP) on intracellular fat accumulation and glucose uptake during differentiation of 3T3 F442A preadipocytes. Total polyphenols were extracted and measured based on gallic acid equivalents (GAE). There were 2167 mg of GAE polyphenols in 100 g of grape powder. 3T3-F442A cells were incubated with GPEP, extracted from 125-500 ug GP/mL of media, until day 8 of differentiation when the cells were collected for different assays. AdipoRedTM assay and Oil Red O staining showed that GPEP induced, in a dose-dependent manner, an increase in intracellular triacylglycerol (TAG) content of adipocytes. Concomitantly, grape powder extracted polyphenols increased, in a dose-dependent manner, glucose uptake by 3T3-F442A cells, and there was a strong positive correlation between glucose uptake and the amount of TAG accumulation (r = 0.826, n = 24, P <= 0.001). No changes in cell viability was measured by Trypan Blue staining, suggesting that these effects were independent of cytotoxicity. Western-blot showed that GPEP upregulated protein level of glucose transport protein 4 (GLUT4), p-PKB/Akt, and p-AMPK in 3T3-F442A adipocytes. LY294002 (10 umol/L), a phosphatidyl-inositol 3 kinase inhibitor (PI3K), reversed the effects of grape powder extracted polyphenols on cellular lipid content and glucose uptake. Furthermore, quantitative real-time polymerase chain reaction showed that GPEP increased mRNA expression of GLUT4, fatty acid synthase, lipoprotein lipase, adiponectin, and peroxisome proliferator-activated receptor gamma, while it decreased mRNA expression of leptin and Insig-1. Our results indicate that GPEP may induce adipocyte differentiation via upregulation of GLUT4, PI3K and adipogenic genes. Future research may be directed toward obese individuals with insulin resistance or individuals with diabetes. PMID- 27190252 TI - Alteration of FXR phosphorylation and sumoylation in liver in the development of adult catch-up growth. AB - Catch-up growth in adult, is increasingly recognized as an important causative factor for the extremely prevalent insulin resistance-related diseases especially in developing countries/territories. We aimed to investigate the alteration of bile acids level, phosphorylation and sumoylation of its interacting protein, bile acid receptor/farnesoid X receptor and their downstream signaling pathway, as well as insulin sensitivity and lipid profile in catch-up growth in adult rats. Male Sprague-Dawley rats were randomly allocated into four groups for two sampling points: caloric restriction group, catch-up growth in adult refed with normal chow and their normal chow controls for four or eight weeks (N4, N8 individually).We found that total serum bile acids and farnesoid X receptor phosphorylation increased without significant changes in farnesoid X receptor sumoylation and its downstream small heterodimer partner expression at the end of caloric restriction stage, while the visceral fat decreased and insulin resistance never occurred in these animals; After refeeding, total serum bile acids, farnesoid X receptor phosphorylation and sumoylation, as well as Cyp7a1, SREBP-1c mRNA levels were higher with significant decrease in small heterodimer partner expression, which is associated fat accumulation, and drastic insulin resistance in whole body and skeletal muscle. Our findings demonstrated that the fat accumulation and insulin resistance are associated with increases of bile acids, alteration of farnesoid X receptor phosphorylation, and sumoylation and its downstream signaling pathway. These changes of bile acids, farnesoid X receptor phosphorylation and sumoylation, as well as their downstream signaling might be of importance in the etiology of fat accumulation and insulin resistance in catch-up growth in adult. PMID- 27190253 TI - Emerging nanotechnologies for cancer immunotherapy. AB - Founded on the growing insight into the complex cancer-immune system interactions, adjuvant immunotherapies are rapidly emerging and being adapted for the treatment of various human malignancies. Immune checkpoint inhibitors, for example, have already shown clinical success. Nevertheless, many approaches are not optimized, require frequent administration, are associated with systemic toxicities and only show modest efficacy as monotherapies. Nanotechnology can potentially enhance the efficacy of such immunotherapies by improving the delivery, retention and release of immunostimulatory agents and biologicals in targeted cell populations and tissues. This review presents the current status and emerging trends in such nanotechnology-based cancer immunotherapies including the role of nanoparticles as carriers of immunomodulators, nanoparticles-based cancer vaccines, and depots for sustained immunostimulation. Also highlighted are key translational challenges and opportunities in this rapidly growing field. PMID- 27190255 TI - Original Research: Analysis of hepatic microRNA alterations in response to hepatitis B virus infection and pegylated interferon alpha-2a treatment. AB - Interferons play important roles in defense mechanisms against viral infection, and thus interferon therapy has been a standard treatment in chronic hepatitis B patients. Interferons signaling pathways promote interferon-inducible genes including microRNAs. In this research, we aimed to determine microRNAs expression profiles in vitro and in vivo For in vitro model, Huh7 cells were transfected with or without hepatitis B virus plasmid for 6 h, and then treated with 100 ng of pegylated-interferon alpha-2a for 24 h. In vivo, we defined microRNAs expression profiles in pair-liver tissues of chronic hepatitis B patients in comparison between before and after treatment of pegylated-interferon alpha-2a for 48 weeks. Cellular small RNAs were extracted followed by library preparation. To determine microRNAs expression profiles, the next-generation sequencing was carried out on MiSeq platform (Illumina(r)). In vitro analysis demonstrated that microRNAs can be classified into up-regulated and down-regulated microRNAs in response to hepatitis B virus, interferon, and combination of hepatitis B virus and interferon. Moreover, in vivo analysis revealed microRNAs profiles in non responders, responders without hepatitis B surface antigen clearance, and responders with hepatitis B surface antigen clearance. The target genes of the candidate microRNAs were determined in terms of roles in cellular pathways and immune response, which might be related to treatment in chronic hepatitis B patients. Results revealed that two down-regulated microRNAs including miR-185-5p and miR-186-5p were correlated in both in vitro and in vivo studies. These two microRNAs might be represented as specific hepatic microRNAs responding to hepatitis B virus and pegylated-interferon alpha-2a treatment, which may remarkable and attractive for further study involving in the association of their target genes and prediction of pegylated-interferon alpha-2a response. Interestingly, microRNAs expression patterns might be useful for understanding the response mechanism and serve as biomarkers for prediction of pegylated interferon alpha-2a treatment response in patients with chronic hepatitis B. PMID- 27190254 TI - Naturally derived biomaterials for addressing inflammation in tissue regeneration. AB - Tissue regeneration strategies have traditionally relied on designing biomaterials that closely mimic features of the native extracellular matrix (ECM) as a means to potentially promote site-specific cellular behaviors. However, inflammation, while a necessary component of wound healing, can alter processes associated with successful tissue regeneration following an initial injury. These processes can be further magnified by the implantation of a biomaterial within the wound site. In addition to designing biomaterials to satisfy biocompatibility concerns as well as to replicate elements of the composition, structure, and mechanics of native tissue, we propose that ECM analogs should also include features that modulate the inflammatory response. Indeed, strategies that enhance, reduce, or even change the temporal phenotype of inflammatory processes have unique potential as future pro-regenerative analogs. Here, we review derivatives of three natural materials with intrinsic anti-inflammatory properties and discuss their potential to address the challenges of inflammation in tissue engineering and chronic wounds. PMID- 27190257 TI - Brief Communication: Featured Article: Histone H2A mono-ubiquitination and cellular transformation are inversely related in N-nitrosodiethylamine-induced hepatocellular carcinoma. AB - Aberrant changes in histone post-translational modifications are encountered frequently in diseases like cancer. Although histone H3 post-translational modifications have been extensively studied in context of diseases, the functionally important histone H2A PTM H2A119ub (H2Aub) has not gained much attention. In this study, we report that H2Aub markedly decreases in hepatocellular carcinoma. Usp21, a H2A deubiquitinase, is probably responsible for decrease in H2Aub. In addition, the H2Aub levels showed an inverse correlation with H3S10 phosphorylation (H3S10p) and the proliferative state of the cells. Downregulation of H2Aub is also associated with increased expression of growth factor gene lipocalin 2. Interestingly, we show that treatment of cells with histone deacetylase inhibitor trichostatin A results in increase of H2Aub and decrease in H3S10p. Our work for the first time suggests the in vivo association of H3S10p, H4ac, and H2A119ub with cellular transformation. PMID- 27190256 TI - Drug delivery strategies to control macrophages for tissue repair and regeneration. AB - Tissue repair and regeneration is a complex process. Our bodies have an excellent capacity to regenerate damaged tissues in many situations. However, tissue healing is impaired in injuries that exceed a critical size or are exacerbated by chronic inflammatory diseases like diabetes. In these instances, biomaterials and drug delivery strategies are often required to facilitate tissue regeneration by providing physical and biochemical cues. Inflammation is the body's response to injury. It is critical for wound healing and biomaterial integration and vascularization, as long as the timing is well controlled. For example, chronic inflammation is well known to impair healing in chronic wounds. In this review, we highlight the importance of a well-controlled inflammatory response, primarily mediated by macrophages in tissue repair and regeneration and discuss various strategies designed to promote regeneration by controlling macrophage behavior. These strategies include temporally controlled delivery of anti-inflammatory drugs, delivery of macrophages as cellular therapy, controlled release of cytokines that modulate macrophage phenotype, and the design of nanoparticles that exploit the inherent phagocytic behavior of macrophages. A clear outcome of this review is that a deeper understanding of the role and timing of complex macrophage phenotypes or activation states is required to fully harness their abilities with drug delivery strategies. PMID- 27190258 TI - Creating biomaterials with spatially organized functionality. AB - Biomaterials for tissue engineering provide scaffolds to support cells and guide tissue regeneration. Despite significant advances in biomaterials design and fabrication techniques, engineered tissue constructs remain functionally inferior to native tissues. This is largely due to the inability to recreate the complex and dynamic hierarchical organization of the extracellular matrix components, which is intimately linked to a tissue's biological function. This review discusses current state-of-the-art strategies to control the spatial presentation of physical and biochemical cues within a biomaterial to recapitulate native tissue organization and function. PMID- 27190260 TI - Platelet-mimetic strategies for modulating the wound environment and inflammatory responses. AB - Platelets closely interface with the immune system to fight pathogens, target wound sites, and regulate tissue repair. Natural platelet levels within the body can be depleted for a variety of reasons, including excessive bleeding following traumatic injury, or diseases such as cancer and bacterial or viral infections. Platelet transfusions are commonly used to improve platelet count and hemostatic function in these cases, but transfusions can be complicated by the contamination risks and short storage life of donated platelets. Lyophilized platelets that can be freeze-dried and stored for longer periods of time and synthetic platelet mimetic technologies that can enhance or replace the functions of natural platelets, while minimizing adverse immune responses have been explored as alternatives to transfusion. Synthetic platelets typically comprise nanoparticles surface-decorated with peptides or ligands to recreate specific biological characteristics of platelets, including targeting of wound and disease sites and facilitating platelet aggregation. Recent efforts in synthetic platelet design have additionally focused on matching platelet shape and mechanics to recreate the marginalization and clot contraction capabilities of natural platelets. The ability to specifically tune the properties of synthetic platelet-mimetic materials has shown utility in a variety of applications including hemostasis, drug delivery, and targeted delivery of cancer therapeutics. PMID- 27190261 TI - Isotetrandrine ameliorates tert-butyl hydroperoxide-induced oxidative stress through upregulation of heme oxygenase-1 expression. AB - 1R, 1'S-isotetrandrine, a naturally occurring plant alkaloid found in Mahonia of Berberidaceae, possesses anti-inflammatory, antibacterial, and antiviral properties, but the antioxidative activity and mechanism action remain unclear. In this study, we demonstrated the antioxidative effect and mechanism of 1R, 1'S isotetrandrine against tert-butyl hydroperoxide-induced oxidative damage in HepG2 cells. We found that 1R, 1'S-isotetrandrine suppressed cytotoxicity, reactive oxygen species generation, and glutathione depletion. Additionally, our study confirmed that 1R, 1'S-isotetrandrine significantly increased the antioxidant enzyme heme oxygenase-1 expression and nuclear translocation of factor-erythroid 2 p45-related factor 2 (Nrf2). Specifically, the nuclear translocation of Nrf2 induced by 1R, 1'S-isotetrandrine was associated with Nrf2 negative regulatory protein Keap1 inactivation and phosphorylation of both extracellular signal regulated protein kinase and c-Jun NH2-terminal kinase. Preincubation with thiol reducing agents reduced 1R, 1'S-isotetrandrine-induced heme oxygenase-1 expression, and treatment with either extracellular signal-regulated protein kinase or c-Jun NH2-terminal kinase inhibitors attenuated the levels of 1R, 1'S isotetrandrine-induced Nrf2 activation and heme oxygenase-1 expression. Furthermore, the cytoprotective effect of 1R, 1'S-isotetrandrine was abolished by heme oxygenase-1, extracellular signal-regulated protein kinase, and c-Jun NH2 terminal kinase inhibitors. These results indicated that the 1R, 1'S isotetrandrine ameliorated tert-butyl hydroperoxide-induced oxidative damage through upregulation of heme oxygenase-1 expression by the dissociation of Nrf2 from Nrf2-Keap1 complex via extracellular signal-regulated protein kinase and c Jun NH2-terminal kinase activation and Keap1 inactivation. PMID- 27190259 TI - Glycomaterials for probing host-pathogen interactions and the immune response. AB - The initial engagement of host cells by pathogens is often mediated by glycan structures presented on the cell surface. Various components of the glycocalyx can be targeted by pathogens for adhesion to facilitate infection. Glycans also play integral roles in the modulation of the host immune response to infection. Therefore, understanding the parameters that define glycan interactions with both pathogens and the various components of the host immune system can aid in the development of strategies to prevent, interrupt, or manage infection. Glycomaterials provide a unique and powerful tool with which to interrogate the compositional and functional complexity of the glycocalyx. The objective of this review is to highlight some key contributions from this area of research in deciphering the mechanisms of pathogenesis and the associated host response. PMID- 27190262 TI - Original Research: The expression of MMP2 and MMP9 in the hippocampus and cerebral cortex of newborn mice under maternal lead exposure. AB - The current study focused on the MMP2 and MMP9 expression in cerebral cortex and hippocampus of newborn mice under maternal lead exposure. Lead exposure was initiated from gestation to weaning. Lead acetate was dissolved in deionized water with concentration of 0.1, 0.2, and 0.5% and was absorbed through daily drinking. On day 21 after birth, lead in blood and tissue levels was examined by Graphite Furnace Atomic Absorption Spectrum (GFAAS). The protein expressions of MMP2 and MMP9 in hippocampus and cerebral cortex tissues were tested by western blotting and immunohistochemistry. Compared to the control group, blood, cerebral cortex, and hippocampus lead levels of newborn mice in 0.1, 0.2, and 0.5% lead exposure groups were markedly high (P < 0.05), and mice within the 0.2 and 0.5% lead exposure groups performed much worse than that of the control group in Water Maze test (P < 0.05). Compared with the control group, MMP2 and MMP9 expressions in hippocampus were up-regulated in the lead exposure groups (P < 0.05), and the MMP2 and MMP9 expressions in cerebral cortex were also higher (P < 0.05). The increased expression of MMP2 and MMP9 in the hippocampus and cerebral cortex may lead to the neurotoxicity in the context of maternal lead exposure. PMID- 27190263 TI - Promoter methylation status of tumor suppressor genes and inhibition of expression of DNA methyltransferase 1 in non-small cell lung cancer. AB - DNA methylation is an epigenetic DNA modification catalyzed by DNA methyltransferase 1 (DNMT1). The purpose of this study was to investigate DNMT1 gene and protein expression and the effects of methylation status on tumor suppressor genes in human non-small cell lung cancer (NSCLC) cell lines grown in vitro and in vivo Human lung adenocarcinoma cell lines, A549 and H838, were grown in vitro and inoculated subcutaneously into nude mice to form tumors and were then treated with the DNA methylation inhibitor, 5-aza-2'-deoxycytidine, with and without treatment with the benzamide histone deacetylase inhibitor, entinostat (MS-275). DNMT1 protein expression was quantified by Western blot. Promoter methylation status of tumor suppressor genes (RASSF1A, ASC, APC, MGMT, CDH13, DAPK, ECAD, P16, and GATA4) was evaluated by methylation-specific polymerase chain reaction. Methylation status of the tumor suppressor genes was regulated by the DNMT1 gene, with the decrease of DNMT1 expression following DNA methylation treatment. Demethylation of tumor suppressor genes (APC, ASC, and RASSF1A) restored tumor growth in nude mice. The results of this study support a role for methylation of DNA as a potential epigenetic clinical biomarker of prognosis or response to therapy and for DNMT1 as a potential therapeutic target in NSCLC. PMID- 27190264 TI - Original Research: Atorvastatin prevents rat cardiomyocyte hypertrophy induced by parathyroid hormone 1-34 associated with the Ras-ERK signaling. AB - We investigated the effects of atorvastatin (Ator) on cardiomyocyte hypertrophy (CMH) induced by rat parathyroid hormone 1-34 (PTH1-34) and Ras-extracellular signal regulated protein kinases 1/2 (ERK1/2) signaling. Rat cardiomyocytes were randomly divided into seven groups: normal controls (NC), PTH1-34 (10(-7) mol/L), Ator (10(-5) mol/L), farnesyl transferase inhibitors-276 (FTI-276, 4 * 10(-5) mol/L), PTH1-34 + Ator, PTH1-34 + FTI-276 and PTH1-34 + Ator + mevalonic acid (MVA, 10(-4) mol/L). After treatment, the hypertrophic responses of cardiomyocytes were assessed by measuring cell diameter, detecting protein synthesis, and single-cell protein content. The concentrations of hypertrophic markers such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were measured by ELISA. Protein expressions of ERK1/2, p-ERK1/2 and Ras were detected by western blotting. The results showed that compared with the PTH1 34 group, cellular diameter, 3H-leucine incorporation, single-cell protein content, ANP and BNP concentration decreased by 12.07 um, 1622 cpm/well, 84.34 pg, 7.13 ng/L and 20.04 ug/L, respectively, and the expressions of Ras and p ERK1/2 were downregulated in PTH1-34 + Ator group (P < 0.05). Compared to the PTH1-34 + Ator group, the corresponding hypertrophic responses and hypertrophic markers increased by 4.95 um, 750 cpm/well, 49.08 pg, 3.12 ng/L and 9.35 ug/L, respectively, and the expressions of Ras and p-ERK1/2 were upregulated in the PTH1-34 + Ator + MVA group (P < 0.05). In conclusion, Ator prevents neonatal rat CMH induced by PTH1-34 and Ras-ERK signaling may be involved in this process. PMID- 27190265 TI - Brief Communication: SIR-2.1-dependent lifespan extension of Caenorhabditis elegans by oxyresveratrol and resveratrol. AB - Resveratrol (RES) has been studied for its effects on the lifespan extension of Caenorhabditis elegans, but controversy still remains on its mechanism related with SIR-2. In this study, longevity assay was performed to confirm SIR-2 dependent lifespan extension of C. elgeans with RES and oxyresveratrol (OXY), an isomer of hydroxylated RES using loss-of-function mutants of C. elegans including sir-2.1 mutant. The results showed that OXY and RES significantly (P < 0.05) extended the lifespan of C. elegans compared with the control. OXY and RES also significantly (P < 0.05) increased the mRNA expression levels of sir-2.1 and aak 2 in a dose-dependent manner and increased the protein expression levels of SIR 2.1. OXY and RES treatment extended the lifespan in daf-16 loss-of-function mutants, which suggested that lifespan extension was not occurring via the activation of DAF-16. However, OXY and RES failed to extend the lifespan in loss of-function mutants of sir-2.1 and aak-2 Therefore, OXY and RES extend the lifespan of C. elegans by overexpression of SIR-2.1, which is related to lifespan extension through calorie restriction and the AMP-activated protein kinase (AMPK) pathway, although this process is independent of the FOXO/DAF-16 pathway. PMID- 27190267 TI - Featured Article: Effect of copper on nuclear translocation of copper chaperone for superoxide dismutase-1. AB - Copper chaperone for superoxide dismutase-1 (CCS-1), facilitating copper insertion into superoxide dismutase 1 (SOD-1), is present in the nucleus. However, it is unknown how CCS-1 is translocated to the nucleus. The present study was undertaken to determine the effect of copper on nuclear translocation of CCS-1. Human umbilical vein endothelial cells (HUVECs) were subjected to hypoxia, causing an increase in both copper and CCS-1 in the nucleus. Treatment with tetraethylenepentamine (TEPA) not only decreased the total cellular concentration and the nuclear translocation of copper, but also completely suppressed the entry of CCS-1 to the nucleus. On the other hand, siRNA targeting CCS-1 neither inhibited the increase in total concentrations nor blocked the nuclear translocation of copper. This study thus demonstrates that under hypoxia condition, both copper and CCS-1 are transported to the nucleus. The nuclear translocation of CCS-1 is copper dependent, but the nuclear translocation of copper could take place alternatively in a CCS-1-independent pathway. PMID- 27190266 TI - Original Research: Different imiquimod creams resulting in differential effects for imiquimod-induced psoriatic mouse models. AB - Imiquimod (IMQ)-induced mouse psoriatic model is one of the useful models displaying most of psoriatic features. To compare the modeling efficacy of different IMQ creams, we induced the psoriatic models by topically applying two different brands of IMQ 5% creams to the shaved Balb/c mice skin and assessed the results. Balb/c female mice (n = 24) 8-12 weeks of age were randomly divided into experimental groups A (Likejie), B (Aldara), and control group C (Vaseline); Likejie, Aldara, or Vaseline was topically applied to the back skin for mice in groups A, B, and C, respectively, for six consecutive days. The total psoriasis area and severity index scores of groups A, B, and C were 3.25 +/- 1.56, 9.81 +/- 0.84, and 0, respectively; the Baker's scores were 2.93 +/- 1.07, 6.47 +/- 1.50, and 0, respectively; and the epidermis thickness was 49.79 +/- 14.16, 85.62 +/- 17.55, and 20.04 +/- 3.68 um, respectively. The differences between the three groups in dual were statistically significant (P < 0.005 for the groups in dual). Aldara group showed more characteristic alterations of psoriasiform lesions than that of Likejie both macroscopically and histopathologically. The results suggested that different brands of IMQ creams may result in differential efficacy when performing the IMQ-induced psoriasis mouse models. PMID- 27190268 TI - Original Research: Establishment of an early embolus-related cerebral injury model after cardiopulmonary bypass in miniature pigs. AB - Embolus-related cerebral injury is still a serious adverse event after cardiopulmonary bypass (CPB). But there is no stable animal model for basic and clinical research purposes. We chose miniature pig to establish a stable animal model of embolus-related cerebral injury after CPB and verified the validity of results by correlating the histopathological findings with those of diffusion weighted magnetic resonance imaging (DW-MRI). Based on different treatment regimens, 24 male miniature pigs were randomly assigned into four groups: Control, CPB, embolus, and CPB-embolus groups. DW-MRI was performed before and after surgery to diagnose and locate the brain lesions. Histopathological changes in brain tissues were examined using H&E and Nissl staining. All surgical procedures were uneventful with 100% postoperative survival of pigs. Two animals in the Embolus group and six animals in the CPB-embolus group showed signs of ischemic penumbra on DW-MRI performed 6 h after surgery. Consistent with the results of DW-MRI, histopathological examination showed necrosis and ischemic lesions. In this paper, we demonstrate the feasibility and validity of a pig model of embolus-related cerebral injury associated with CPB. This model may be used in the future for basic and translational research. PMID- 27190269 TI - Copper, iron, and selenium dietary deficiencies negatively impact skeletal integrity: A review. AB - Nutrients have been known to have a significant role in maintaining the health of the skeleton, both bone and cartilage. The nutrients that have received the majority of the attention are Vitamin D and calcium. However, limited attention has been directed toward three trace elements that may have mechanistic impact upon the skeletal tissues and could compromise skeletal health resulting from inadequate intakes of copper, iron, and selenium. The role of copper and selenium has been known, but the role of iron has only received recent attention. Copper deficiency is thought to impact bone health by a decrease in lysyl oxidase, a copper-containing enzyme, which facilitates collagen fibril crosslinking. Iron deficiency impact upon bone has only recently been discovered but the exact mechanism on how the deficient states enhance bone pathology is speculative. Selenium deficiency has an impact on cartilage thereby having an indirect impact on bone. However, several studies suggest that a mycotoxin when consumed by humans is the culprit in some cartilage disorders and the presence of selenium could attenuate the pathology. This review summarizes the current knowledge base with respect to skeletal integrity when each of these three trace elements are inadequate in diets of both animals and humans. PMID- 27190270 TI - Original Research: Label-free detection for radiation-induced apoptosis in glioblastoma cells. AB - Current flow cytometry (FCM) requires fluorescent dyes labeling cells which make the procedure costly and time consuming. This manuscript reports a feasibility study of detecting the cell apoptosis with a label-free method in glioblastoma cells. A human glioma cell line M059K was exposed to 8 Gy dose of radiation, which enables the cells to undergo radiation-induced apoptosis. The rates of apoptosis were studied at different time points post-irradiation with two different methods: FCM in combination with Annexin V-FITC/PI staining and a newly developed technique named polarization diffraction imaging flow cytometry. Totally 1000 diffraction images were acquired for each sample and the gray level co-occurrence matrix (GLCM) algorithm was used in morphological characterization of the apoptotic cells. Among the feature parameters extracted from each image pair, we found that the two GLCM parameters of angular second moment (ASM) and sum entropy (SumEnt) exhibit high sensitivities and consistencies as the apoptotic rates (Pa) measured with FCM method. In addition, no significant difference exists between Pa and ASM_S, Pa and SumEnt_S, respectively (P > 0.05). These results demonstrated that the new label-free method can detect cell apoptosis effectively. Cells can be directly used in the subsequent biochemical experiments as the structure and function of cells and biomolecules are well preserved with this new method. PMID- 27190272 TI - Gene-gene interaction of erythropoietin gene polymorphisms and diabetic retinopathy in Chinese Han. AB - The aim of this study was to investigate the association of three single nucleotide polymorphisms in the erythropoietin gene polymorphisms with diabetic retinopathy and additional role of gene-gene interaction on diabetic retinopathy risk. A total of 1193 patients (579 men, 614 women) with type 2 diabetes mellitus were selected, including 397 diabetic retinopathy patients and 796 controls (type 2 diabetes mellitus patients without diabetic retinopathy); the mean age of all participants was 56.7 +/- 13.9 years. Three single nucleotide polymorphisms were selected: rs507392, rs1617640, and rs551238. The t-test was used for comparison of erythropoietin protein level erythropoietin levels in patients having different erythropoietin genotypes. Logistic regression model was used to examine the association between three single nucleotide polymorphisms and diabetic retinopathy. Odds ratio (OR) and 95% confident interval (95% CI) were calculated. Generalized multifactor dimensionality reduction was employed to analyze the impact of interaction among three single nucleotide polymorphisms on CVD risk. After covariates adjustment, the carriers of homozygous mutant of three single nucleotide polymorphisms have higher diabetic retinopathy risk than those with wild-type homozygotes, OR (95% CI) were 2.04 (1.12-2.35), 1.87 (1.10-2.41) and 1.15 (1.06-1.76), respectively. Generalized multifactor dimensionality reduction model indicated a significant three-locus model (p = 0.0010) involving rs507392, rs1617640, and rs551238. Overall, the three-locus models had a cross-validation consistency of 10 of 10, and had the testing accuracy of 60.72%. Subjects with TC or CC-TG or GG-AC or CC genotype have the highest diabetic retinopathy risk. In conclusion, our results support an important association of rs507392, rs1617640 and rs551238 minor allele of erythropoietin with increased diabetic retinopathy risk, and additional interaction among three single nucleotide polymorphisms. PMID- 27190271 TI - Deciphering signaling networks in osteosarcoma pathobiology. AB - Osteosarcoma is the most frequent type of primary bone tumors among children and adolescents. During the past years, little progress has been made regarding prognosis of osteosarcoma patients, especially for those with metastatic disease. Genomic instability and gene alterations are common, but current data do not reveal a consistent and repeatable pattern of osteosarcoma development, thus paralleling the tumor's high heterogeneity. Critical signal transduction pathways have been implicated in osteosarcoma pathobiology and are being evaluated as therapeutic targets, including receptor activator for nuclear factor-kappaB (RANK), Wnt, Notch, phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin, and mechanotransduction pathways. Herein, we recapitulate and discuss recent advances in the context of molecular mechanisms and signaling networks that contribute to osteosarcoma progression and metastasis, towards patient tailored and novel-targeted treatments. PMID- 27190273 TI - The use of CD47-modified biomaterials to mitigate the immune response. AB - Addressing the aberrant interactions between immune cells and biomaterials represents an unmet need in biomaterial research. Although progress has been made in the development of bioinert coatings, identifying and targeting relevant cellular and molecular pathways can provide additional therapeutic strategies to address this major healthcare concern. To that end, we describe the immune inhibitory motif, receptor-ligand pairing of signal regulatory protein alpha and its cognate ligand CD47 as a potential signaling pathway to enhance biocompatibility. The goals of this article are to detail the known roles of CD47 signal regulatory protein alpha signal transduction pathway and to describe how immobilized CD47 can be used to mitigate the immune response to biomaterials. Current applications of CD47-modified biomaterials will also be discussed herein. PMID- 27190274 TI - Polyunsaturated fatty acid induces cardioprotection against ischemia-reperfusion through the inhibition of NF-kappaB and induction of Nrf2. AB - The mechanistic evidence to support the cardioprotective effects of polyunsaturated fatty acids (PUFA) are controversial. The aim was to test cardioprotective mechanisms induced by PUFA supplementation against cardiac ischemia-reperfusion (IR) injury. Ten-week-old male Wistar rats (225 +/- 14 g, n = 14) were divided in two groups: rats without supplementation ( n = 7) and a PUFA group, supplemented by PUFA (0.6 g/kg/day; DHA:EPA = 3:1) for eight weeks ( n = 7). Hearts were perfused with Krebs-Henseleit buffer for 20 min (control conditions); others were subjected to control conditions, 30 min of global ischemia and 120 min of reperfusion (IR group). Infarct size (IS) and left ventricular developed pressure (LVDP) were measured at 120 min of reperfusion. Oxidative stress biomarkers (TBARS, total carbonyls), antioxidant status (CAT, catalase; SOD, superoxide dismutase; GSH-Px, glutathione peroxidase activity and GSH/GSSG ratio), myeloperoxidase activity, ATP levels and nuclear transcription factor erythroid 2-related factor 2 (Nrf2) and nuclear factor kappaB (NF-kappaB) were determined in both experimental conditions. At the end of reperfusion, hearts supplemented with PUFA showed lower IS and a higher LVDP compared with the nonsupplemented rats. Hearts in the group supplemented with PUFA showed lower levels of oxidative stress markers and higher antioxidant activity, decreased MPO activity and NF-kappaB and Nrf2 activation compared with the nonsupplemented group. Cardioprotective effects of PUFA are exerted through induction of anti inflammatory and antioxidant mechanism at tissue level. PMID- 27190275 TI - Original Research: Orexins A and B stimulate proliferation and differentiation of porcine preadipocytes. AB - Orexin A (OXA) and B (OXB) are neuropeptides which regulate appetite, energy expenditure, and arousal via G-protein coupled receptors termed as OXR1 and OXR2. The aim of this study was to characterize the effects of OXA and OXB on proliferation and differentiation of porcine preadipocytes. Porcine preadipocytes express both OXRs. OXA and OXB enhance porcine preadipocyte proliferation by 54.8% or 63.2 %, respectively. OXA and OXB potentiate differentiation of porcine preadipocytes, as judged by the increased lipid accumulation and expression of proadipogenic genes. Cellular lipid content after exposure of preadipocytes for six days to 100 nM OXA or OXB increased by 82.2% or 59.2%, respectively. OXA and OXB suppressed glycerol release by 23.9% or 24.9% in preadipocytes differentiated for six days. OXA (100 nM) increased peroxisome proliferator-activated receptor gamma (PPARgamma) expression in cells differentiated for 24 h by 100.5%. PPARgamma expression was also stimulated in preadipocytes differentiated in the presence of 10 nM (58.3%) or 100 nM OXA (50.6%) for three days. OXB potentiated PPARgamma mRNA expression at 1 nM (59%), 10 nM (53.2%), and 100 nM (73.9%) in cells differentiated for three days. OXA increased CCAAT/enhancer binding protein alpha expression in preadipocytes differentiated for six days by 65%. OXB stimulated CCAAT/enhancer binding protein beta expression in preadipocytes differentiated for three days at 10 nM (149.5%) as well as 100 nM (207.2%). Lipoprotein lipase mRNA expression increased in cells treated with 10 nM OXA by 152.6% and 100 nM OXA by 162%. Lipoprotein lipase expression increased by 134% at 100 nM OXB. Furthermore, OXA (100 nM) and OXB (100 nM) increased leptin mRNA expression in preadipocytes differentiated for three days by 49.9% or 71.3%, respectively. These data indicate that orexin receptors may be relevant in the context of white adipose tissue formation. PMID- 27190277 TI - Resveratrol counters systemic lupus erythematosus-associated atherogenicity by normalizing cholesterol efflux. AB - Resveratrol is a bioactive molecule used in dietary supplements and herbal medicines and consumed worldwide. Numerous investigations by our group and others have indicated cardioprotective and anti-inflammatory properties of resveratrol. The present study explored potential atheroprotective actions of resveratrol on cholesterol efflux in cultured human macrophages exposed to plasma from systemic lupus erythematosus (SLE) patients. These results were confirmed in ApoE(-/-)Fas( /-) double knockout mice, displaying a lupus profile with accelerated atherosclerosis. Resveratrol treatment attenuated atherosclerosis in these mice. THP-1 human macrophages were exposed to 10% pooled or individual plasma from patients who met diagnostic criteria for SLE. Expression of multiple proteins involved in reverse cholesterol transport (ABCA1, ABCG1, SR-B1, and cytochrome P450 27-hydroxylase) was assessed using QRT-PCR and Western blotting techniques. Ten-week-old ApoE(-/-)Fas(-/-) double knockout mice (n = 30) were randomly divided into two equal groups of 15, one of which received 0.01% resveratrol for 10 consecutive weeks. Atherosclerosis progression was evaluated in murine aortas. Bone marrow-derived macrophages (BMDM) were cultured and expression of cholesterol efflux proteins was analyzed in each group of mice. Our data indicate that inhibition of cholesterol efflux by lupus plasma in THP-1 human macrophages is rescued by resveratrol. Similarly, administration of resveratrol in a lupus like murine model reduces plaque formation in vivo and augments cholesterol efflux in BMDM. This study presents evidence for a beneficial role of resveratrol in atherosclerosis in the specific setting of SLE. Therefore, resveratrol may merit investigation as an additional resource available to reduce lipid deposition and atherosclerosis in humans, especially in such vulnerable populations as lupus patients. PMID- 27190278 TI - Detection of expressional changes induced by intrauterine growth restriction in the developing rat pancreas. AB - Intrauterine growth retardation (IUGR) is a disorder that can result in permanent changes in the physiology and metabolism of the newborn, which increased the risk of disease in adulthood. Evidence supports IUGR as a risk factor for the development of diabetes mellitus, which could reflect changes in pancreas developmental pathways. We sought to characterize the IUGR-induced alterations of the complex pathways of pancreas development in a rat model of IUGR. We analyzed the pancreases of Sprague Dawley rats after inducing IUGR by feeding a maternal low calorie diet from gestational day 1 until term. IUGR altered the pancreatic structure, islet areas, and islet quantities and resulted in abnormal morphological changes during pancreatic development, as determined by HE staining and light microscopy. We identified multiple differentially expressed genes in the pancreas by RT-PCR. The genes of the insulin/FoxO1/Pdx1/MafA signaling pathway were first expressed at embryonic day 14 (E14). The expressions of insulin and MafA increased as the fetus grew while the expressions of FoxO1 and Pdx1 decreased. Compared with the control rats, the expressions of FoxO1, Pdx1, and MafA were lower in the IUGR rats, whereas insulin levels showed no change. Microarray profiling, in combination with quantitative real-time PCR, uncovered a subset of microRNAs that changed in their degree of expression throughout pancreatic development. In conclusion, our data support the hypothesis that IUGR influences the development of the rat pancreas. We also identified new pathways that appear to be programmed by IUGR. PMID- 27190279 TI - Differential Time Course of Microstructural White Matter in Patients With Psychotic Disorder and Individuals at Risk: A 3-Year Follow-up Study. AB - BACKGROUND: Although widespread reduced white matter (WM) integrity is a consistent finding in cross-sectional diffusion tensor imaging (DTI) studies of schizophrenia, little is known about the course of these alterations. This study examined to what degree microstructural WM alterations display differential trajectories over time as a function of level of psychosis liability. METHODS: Two DTI scans with a 3-year time interval were acquired from 159 participants (55 patients with a psychotic disorder, 55 nonpsychotic siblings and 49 healthy controls) and processed with tract-based spatial statistics. The mean fractional anisotropy (FA) change over time was calculated. Main effects of group, as well as group * region interactions in the model of FA change were examined with multilevel (mixed-effects) models. RESULTS: Siblings revealed a significant mean FA decrease over time compared to controls (B = -0.004, P = .04), resulting in a significant sibling-control difference at follow-up (B = -0.007, P = .03). Patients did not show a significant change over time, but their mean FA was lower than controls both at baseline and at follow-up. A significant group * region interaction (chi2 = 105.4, P = .01) revealed group differences in FA change in the right cingulum, left posterior thalamic radiation, right retrolenticular part of the internal capsule, and the right posterior corona radiata. CONCLUSION: Whole brain mean FA remained stable over a 3-year period in patients with psychotic disorder and declined over time in nonaffected siblings, so that at follow-up both groups had lower FA with respect to controls. The results suggest that liability for psychosis may involve a process of WM alterations. PMID- 27190276 TI - Intermittent hypoxia training protects cerebrovascular function in Alzheimer's disease. AB - Alzheimer's disease (AD) is a leading cause of death and disability among older adults. Modifiable vascular risk factors for AD (VRF) include obesity, hypertension, type 2 diabetes mellitus, sleep apnea, and metabolic syndrome. Here, interactions between cerebrovascular function and development of AD are reviewed, as are interventions to improve cerebral blood flow and reduce VRF. Atherosclerosis and small vessel cerebral disease impair metabolic regulation of cerebral blood flow and, along with microvascular rarefaction and altered trans capillary exchange, create conditions favoring AD development. Although currently there are no definitive therapies for treatment or prevention of AD, reduction of VRFs lowers the risk for cognitive decline. There is increasing evidence that brief repeated exposures to moderate hypoxia, i.e. intermittent hypoxic training (IHT), improve cerebral vascular function and reduce VRFs including systemic hypertension, cardiac arrhythmias, and mental stress. In experimental AD, IHT nearly prevented endothelial dysfunction of both cerebral and extra-cerebral blood vessels, rarefaction of the brain vascular network, and the loss of neurons in the brain cortex. Associated with these vasoprotective effects, IHT improved memory and lessened AD pathology. IHT increases endothelial production of nitric oxide (NO), thereby increasing regional cerebral blood flow and augmenting the vaso- and neuroprotective effects of endothelial NO. On the other hand, in AD excessive production of NO in microglia, astrocytes, and cortical neurons generates neurotoxic peroxynitrite. IHT enhances storage of excessive NO in the form of S-nitrosothiols and dinitrosyl iron complexes. Oxidative stress plays a pivotal role in the pathogenesis of AD, and IHT reduces oxidative stress in a number of experimental pathologies. Beneficial effects of IHT in experimental neuropathologies other than AD, including dyscirculatory encephalopathy, ischemic stroke injury, audiogenic epilepsy, spinal cord injury, and alcohol withdrawal stress have also been reported. Further research on the potential benefits of IHT in AD and other brain pathologies is warranted. PMID- 27190282 TI - A Positive Detour. PMID- 27190280 TI - Predictive Motor Timing and the Cerebellar Vermis in Schizophrenia: An fMRI Study. AB - Abnormalities in both time processing and dopamine (DA) neurotransmission have been observed in schizophrenia. Time processing seems to be linked to DA neurotransmission. The cognitive dysmetria hypothesis postulates that psychosis might be a manifestation of the loss of coordination of mental processes due to impaired timing. The objective of the present study was to analyze timing abilities and their corresponding functional neuroanatomy in schizophrenia. We performed a functional magnetic resonance imaging (fMRI) study using a predictive motor timing paradigm in 28 schizophrenia patients and 27 matched healthy controls (HC). The schizophrenia patients showed accelerated time processing compared to HC; the amount of the acceleration positively correlated with the degree of positive psychotic symptoms and negatively correlated with antipsychotic dose. This dysfunctional predictive timing was associated with BOLD signal activity alterations in several brain networks, especially those previously described as timing networks (basal ganglia, cerebellum, SMA, and insula) and reward networks (hippocampus, amygdala, and NAcc). BOLD signal activity in the cerebellar vermis was negatively associated with accelerated time processing. Several lines of evidence suggest a direct link between DA transmission and the cerebellar vermis that could explain their relevance for the neurobiology of schizophrenia. PMID- 27190283 TI - Characterization of a highly potent antimicrobial peptide microcin N from uropathogenic Escherichia coli. AB - Microcin N is a low-molecular weight, highly active antimicrobial peptide produced by uropathogenic Escherichia coli In this study, the native peptide was expressed and purified from pGOB18 plasmid carrying E. coli in low yield. The pure peptide was characterized using mass spectrometry, N-terminal sequencing by Edman degradation as well as trypsin digestion. We found that the peptide is 74 residue long, cationic (+2 total charge), highly hydrophobic and consists of glycine as the first N-terminal residue. The minimum inhibitory concentration of the peptide against Salmonella enteritidis was found to be 150 nM. Evaluation of the solution conformation of the peptide using circular dichroism spectroscopy showed that the peptide is well folded in 40% trifluoroethanol with helical structure whereas the folded structure is lost in aqueous solution. To increase the yield of this potent peptide, we overexpressed GST-tagged microcin N using E. coli BL21. Recombinant GST-tagged microcin N was successfully expressed in E. coli BL21; however, the cleaved mature microcin N did not show activity against the indicator strain (S. enterica) most likely due to the extreme hydrophobic nature of the peptide. Efforts to produce active microcin N in large scale are discussed as this peptide has huge potential to be the next generation antimicrobial agent. PMID- 27190281 TI - White Matter Abnormalities Associated With Subsyndromal Psychotic-Like Symptoms Predict Later Social Competence in Children and Adolescents. AB - INTRODUCTION: Recent data suggest that healthy children and adolescents who report psychotic-like experiences (PLEs) evidence abnormalities in white matter (WM). To date, no study has examined whether WM abnormalities associated with PLEs are predictive of outcome at a later time-point. The present study examined whether abnormalities in WM associated with PLEs in children and adolescents at a baseline assessment were predictive of social functioning at a 12-month follow up. SUBJECTS AND METHODS: Healthy children and adolescents aged 8-18 years (N = 56) were recruited from the community and received a diffusion tensor imaging exam and a clinical exam at baseline. Voxel-wise statistical analysis of fractional anisotropy (FA), using Tract-Based Spatial Statistics, and probabilistic tractography were used to identify WM abnormalities associated with PLEs at baseline. These abnormalities were then examined for association to social problems and social competence in 28 participants at 12-month follow-up. RESULTS: Lower FA in regions proximal to the superior longitudinal fasciculus (SLF) and corticospinal tract bilaterally as well as in the left inferior fronto occipital fasciculus and inferior longitudinal fasciculus were associated with higher levels of PLEs at baseline. Moreover, baseline FA in the SLF, but not baseline severity of PLEs, was significantly predictive of social competence at a 12-month follow-up. In contrast, baseline severity of PLEs, but not baseline FA in the SLF, predicted social problems at 12-month follow-up. DISCUSSION: These findings suggest that alterations in WM, which are associated with symptoms of psychosis well below the threshold of clinical significance, may have significant ramifications for later social development. PMID- 27190284 TI - Vitamin C induced DevR-dependent synchronization of Mycobacterium smegmatis growth and its effect on the proliferation of mycobacteriophage D29. AB - Vitamin C is known to inhibit mycobacterial growth by acting as a hypoxia inducing agent. While investigating how mycobacteriophage growth is influenced by hypoxic conditions induced by vitamin C, using Mycobacterium smegmatis- mycobacteriophage D29 as a model system, it was observed that prior exposure of the host to such conditions resulted in increased burst size of the phage. Vitamin C pre-exposure was also found to induce synchronous growth of the host. A mutant defective in DevR, the response regulator that controls hypoxic responses in mycobacteria, neither supported higher phage bursts nor was it able to undergo synchronized growth following vitamin C pre-exposure, indicating thereby that the two phenomena are interrelated. Further evidence supporting such an interrelationship was obtained from the observation that phage burst sizes varied depending on the stage of synchronous growth that the host cells were in, at the time of infection-higher bursts were observed in the resting/synthetic phases and lower in the dividing ones. The effects were specific in nature as synchronization by an unrelated method, known as 'crowding', did not lead to the same consequence. The results indicate that growth synchronization induced by vitamin C treatment is a DevR-dependent phenomenon which is exploited by mycobacteriophage D29 to grow in larger numbers. PMID- 27190286 TI - Contribution of chloride channel permease to fluoride resistance in Streptococcus mutans. AB - Genes encoding fluoride transporters have been identified in bacterial and archaeal species. The genome sequence of the cariogenic Streptococcus mutans bacteria suggests the presence of a putative fluoride transporter, which is referred to as a chloride channel permease. Two homologues of this gene (GenBank locus tags SMU_1290c and SMU_1289c) reside in tandem in the genome of S. mutans The aim of this study was to determine whether the chloride channel permeases contribute to fluoride resistance. We constructed SMU_1290c- and SMU_1289c knockout S. mutans UA159 strains. We also constructed a double-knockout strain lacking both genes. SMU_1290c or SMU_1289c was transformed into a fluoride transporter- disrupted Escherichia coli strain. All bacterial strains were cultured under appropriate conditions with or without sodium fluoride, and fluoride resistance was evaluated. All three gene-knockout S. mutans strains showed lower resistance to sodium fluoride than did the wild-type strain. No significant changes in resistance to other sodium halides were recognized between the wild-type and double-knockout strains. Both SMU_1290c and SMU_1289c transformation rescued fluoride transporter-disrupted E. coli cell from fluoride toxicity. We conclude that the chloride channel permeases contribute to fluoride resistance in S. mutans. PMID- 27190285 TI - Properties and biotechnological applications of ice-binding proteins in bacteria. AB - Ice-binding proteins (IBPs), such as antifreeze proteins (AFPs) and ice nucleating proteins (INPs), have been described in diverse cold-adapted organisms, and their potential applications in biotechnology have been recognized in various fields. Currently, both IBPs are being applied to biotechnological processes, primarily in medicine and the food industry. However, our knowledge regarding the diversity of bacterial IBPs is limited; few studies have purified and characterized AFPs and INPs from bacteria. Phenotypically verified IBPs have been described in members belonging to Gammaproteobacteria, Actinobacteria and Flavobacteriia classes, whereas putative IBPs have been found in Gammaproteobacteria, Alphaproteobacteria and Bacilli classes. Thus, the main goal of this minireview is to summarize the current information on bacterial IBPs and their application in biotechnology, emphasizing the potential application in less explored fields such as agriculture. Investigations have suggested the use of INP producing bacteria antagonists and AFPs-producing bacteria (or their AFPs) as a very attractive strategy to prevent frost damages in crops. UniProt database analyses of reported IBPs (phenotypically verified) and putative IBPs also show the limited information available on bacterial IBPs and indicate that major studies are required. PMID- 27190287 TI - Resistance-nodulation-division efflux pump acrAB is modulated by florfenicol and contributes to drug resistance in the fish pathogen Piscirickettsia salmonis. AB - Piscirickettsia salmonis is a fastidious intracellular pathogen responsible for high mortality rates in farmed salmonids, with serious economic consequences for the Chilean aquaculture industry. Oxytetracycline and florfenicol are the most frequently used antibiotics against P. salmonis, but routine use could contribute to drug resistance. This study identified differentiated florfenicol susceptibilities in two P. salmonis strains, LF-89 and AUSTRAL-005. The less susceptible isolate, AUSTRAL-005, also showed a high ethidium bromide efflux rate, indicating a higher activity of general efflux pump genes than LF-89. The P. salmonis genome presented resistance nodulation division (RND) family members, a family containing typical multidrug resistance-related efflux pumps in Gram negative bacteria. Additionally, efflux pump acrAB genes were overexpressed in AUSTRAL-005 following exposure to the tolerated maximal concentration of florfenicol, in contrast to LF-89. These results indicate that tolerated maximum concentrations of florfenicol can modulate RND gene expression and increase efflux pump activity. We propose that the acrAB efflux pump is essential for P. salmonis survival at critical florfenicol concentrations and for the generation of antibiotic-resistant bacterial strains. PMID- 27190288 TI - Microbial impact on polysulfide dynamics in the environment. AB - Polysulfides (Sx (2-)) are sulfide oxidation intermediates that are important for a variety of environmentally relevant processes including pyrite formation, organic matter sulfidization, isotope exchange among reduced sulfur species, and metal chelation. In addition to their chemical reactivity, laboratory experiments with microbial cultures and enzymes indicate both indirect and direct roles for microorganisms in affecting polysulfide chemistry in natural environments through production and consumption. As polysulfides have been detected in a wide array of natural systems ranging from microbial mats to hydrothermal vents, constraining their biogeochemical cycling has broad impacts. However, many questions remain regarding the processes responsible for polysulfide dynamics in these environments and the precise role that microorganisms play in these processes. This review provides a summary of laboratory experiments investigating the role of polysulfides in microbial metabolism, and observations of polysulfides in the environment in order to provide further insight into and highlight open questions about this significant component of the sulfur cycle. PMID- 27190290 TI - Widespread ability of fungi to drive quinone redox cycling for biodegradation. AB - Wood-rotting fungi possess remarkably diverse extracellular oxidation mechanisms, including enzymes, such as laccase and peroxidases, and Fenton chemistry. The ability to biologically drive Fenton chemistry by the redox cycling of quinones has previously been reported to be present in both ecologically diverging main groups of wood-rotting basidiomycetes. Therefore, we investigated whether it is even more widespread among fungal organisms. Screening of a diverse selection of a total of 18 ascomycetes and basidiomycetes for reduction of the model compound 2,6-dimethoxy benzoquinone revealed that all investigated strains were capable of reducing it to its corresponding hydroquinone. In a second step, depolymerization of the synthetic polymer polystyrene sulfonate was used as a proxy for quinone dependent Fenton-based biodegradation capabilities. A diverse subset of the strains, including environmentally ubiquitous molds, white-rot fungi, as well as peatland and aquatic isolates, caused substantial depolymerization indicative for the effective employment of quinone redox cycling as biodegradation tool. Our results may also open up new paths to utilize diverse fungi for the bioremediation of recalcitrant organic pollutants. PMID- 27190289 TI - The ferrichrome receptor A as a new target for Pseudomonas aeruginosa virulence attenuation. AB - Pseudomonas aeruginosa is an opportunistic pathogen, known to develop robust biofilms. Its biofilm development increases when antibiotics are presented at subminimal inhibitory concentrations (MICs) for reasons that remain unclear. In order to identify genes that affect biofilm development under such a sublethal antibiotic stress condition, we screened a transposon (Tn) mutant library of PAO1, a prototype P. aeruginosa strain. Among ~5000 mutants, a fiuA gene mutant was verified to form very defective biofilms in the presence of sub-MIC carbenicillin. The fiuA gene encodes ferrichrome receptor A, involved in the iron acquisition process. Of note, biofilm formation was not decreased in the DeltapchDeltapvd mutant defective in the production of pyochelin and pyoverdine, two well-characterized P. aeruginosa siderophore molecules. Moreover, DeltafiuA, a non-polar fiuA deletion mutant, produced a significantly decreased level of elastase, a major virulence determinant. Mouse airway infection experiments revealed that the mutant expressed significantly less pathogenicity. Our results suggest that the fiuA gene has pleiotropic functions that affect P. aeruginosa biofilm development and virulence. The targeting of FiuA could enable the attenuation of P. aeruginosa virulence and may be suitable for the development of a drug that specifically controls the virulence of this important pathogen. PMID- 27190292 TI - Nicotinamide cofactor ratios in engineered strains of Clostridium thermocellum and Thermoanaerobacterium saccharolyticum. AB - Clostridium thermocellum and Thermoanaerobacterium saccharolyticum are bacteria under investigation for production of biofuels from plant biomass. Thermoanaerobacterium saccharolyticum has been engineered to produce ethanol at high yield (>90% of theoretical) and titer (>70 g/l). Efforts to engineer C. thermocellum have not, to date, been as successful, and efforts are underway to transfer the ethanol production pathway from T. saccharolyticum to C. thermocellum One potential challenge in transferring metabolic pathways is the possibility of incompatible levels of nicotinamide cofactors. These cofactors (NAD(+), NADH, NADP(+) and NADPH) and their oxidation state are important in the context of microbial redox metabolism. In this study we directly measured the concentrations and reduced oxidized ratios of these cofactors in a number of strains of C. thermocellum and T. saccharolyticum by using acid/base extraction and enzymatic assays. We found that cofactor ratios are maintained in a fairly narrow range, regardless of the metabolic network modifications considered. We have found that the ratios are similar in both organisms, which is a relevant observation in the context of transferring the T. saccharolyticum ethanol production pathway to C. thermocellum. PMID- 27190291 TI - Endophytic fungi associated with Sudanese medicinal plants show cytotoxic and antibiotic potential. AB - In this study, we isolated 15 endophytic fungi from five Sudanese medicinal plants. Each fungal endophytic strain was identified by sequencing of internal transcribed spacer (ITS) regions of rDNA. Ethyl acetate extracts were prepared from each endophyte cultivated in vitro and tested for their respective antibacterial activities and antiproliferative activities against human cancer cells. Antibacterial screening was carried out against two bacterial strains: Gram-negative Escherichia coli and Gram-positive methicillin-resistant Staphylococcus aureus, by the broth dilution method. Cell viability was evaluated by the MTT procedure after exposure of MCF7 breast cancer cells and HT29 or HCT116 human colon adenocarcinoma cells to each endophytic extract. Of interest, Byssochlamys spectabilis isolated from Euphorbia prostata showed cytotoxicity (IC50 = 1.51 +/- 0.2 MUg mL(-1)) against MCF7 cells, but had a low effect against HT29 or HCT116 cells (IC50 > 20 MUg mL(-1)). Cladosporium cladosporioides 2, isolated from Vernonia amygdalina leaves, showed antiproliferative activities against MCF7 cells (IC50 = 10.5 +/- 1.5 MUg mL(-1)) only. On the other hand, B. spectabilis and Alternaria sp. extract had antibacterial activities against the S. aureus strain. The findings of this work revealed that endophytic fungi associated with medicinal plants from Sudan could be considered as an attractive source of new therapeutic compounds. PMID- 27190293 TI - A case in support of implementing innovative bio-processes in the metal mining industry. AB - The metal mining industry faces many large challenges in future years, among which is the increasing need to process low-grade ores as accessible higher grade ores become depleted. This is against a backdrop of increasing global demands for base and precious metals, and rare earth elements. Typically about 99% of solid material hauled to, and ground at, the land surface currently ends up as waste (rock dumps and mineral tailings). Exposure of these to air and water frequently leads to the formation of acidic, metal-contaminated run-off waters, referred to as acid mine drainage, which constitutes a severe threat to the environment. Formation of acid drainage is a natural phenomenon involving various species of lithotrophic (literally 'rock-eating') bacteria and archaea, which oxidize reduced forms of iron and/or sulfur. However, other microorganisms that reduce inorganic sulfur compounds can essentially reverse this process. These microorganisms can be applied on industrial scale to precipitate metals from industrial mineral leachates and acid mine drainage streams, resulting in a net improvement in metal recovery, while minimizing the amounts of leachable metals to the tailings storage dams. Here, we advocate that more extensive exploitation of microorganisms in metal mining operations could be an important way to green up the industry, reducing environmental risks and improving the efficiency and the economy of metal recovery. PMID- 27190295 TI - Purification, characterization, and function analysis of an extracellular beta glucosidase from elongating stipe cell walls in Coprinopsis cinerea. PMID- 27190294 TI - Cloning, expression and mutation of a triazophos hydrolase gene from Burkholderia sp. SZL-1. AB - Triazophos is a broad-spectrum and highly effective insecticide, and the residues of triazophos have been frequently detected in the environment. A triazophos degrading bacterium, Burkholderia sp. SZL-1, was isolated from a long-term triazophos-polluted soil. Strain SZL-1 could hydrolyze triazophos to 1-phenyl-3 hydroxy-1,2,4-triazole, which was further utilized as the carbon sources for growth. The triazophos hydrolase gene trhA, cloned from strain SZL-1, was expressed and homogenously purified using Ni-nitrilotriacetic acid affinity chromatography. TrhA is 55 kDa and displays maximum activity at 25 degrees C, pH 8.0. This enzyme still has nearly 60% activity at the range of 15 degrees C-50 degrees C for 30 min. TrhA was mutated by sequential error prone PCR and screened for improved activity for triazophos degradation. One purified variant protein (Val89-Gly89) named TrhA-M1 showed up to 3-fold improvement in specific activity against triazophos, and the specificity constants of Kcat and Kcat/Km for TrhA-M1 were improved up to 2.3- and 8.28-fold, respectively, compared to the wild-type enzyme. The results in this paper provided potential material for the contaminated soil remediation and hydrolase genetic structure research. PMID- 27190296 TI - Sickle cell disease severity: an introduction. PMID- 27190303 TI - A novel microfluidic assay reveals a key role for protein kinase C delta in regulating human neutrophil-endothelium interaction. AB - A key step in neutrophil-mediated tissue damage is the migration of activated neutrophils across the vascular endothelium. Previously, we identified protein kinase C delta as a critical regulator of neutrophil migration in sepsis but did not identify specific steps in migration. In this study, we used our novel biomimetic microfluidic assay to delineate systematically the mechanism by which protein kinase C delta regulates individual steps in human neutrophil-endothelial interaction during inflammation. The biomimetic microfluidic assay includes a network of vascular channels, produced from in vivo images connected to a tissue compartment through a porous barrier. HUVECs cultured in vascular channels formed a complete lumen under physiologic shear flow. HUVECs were pretreated with TNF alpha +/- a protein kinase C delta inhibitor, and the tissue compartment was filled with a chemoattractant (fMLP or IL-8). Under physiologic shear flow, the role of protein kinase C delta on spatial and temporal neutrophil adherence/migration was quantified. Protein kinase C delta inhibition significantly reduced neutrophil adhesion in response to fMLP and IL-8 only under low shear rate and near bifurcations. Protein kinase C delta inhibition also decreased adherence to nonactivated HUVECs in response to fMLP or IL-8. Protein kinase C delta inhibition reduced neutrophil migration into the tissue compartment in response to fMLP and to a lesser degree, to IL-8. Antibody-coated microparticles demonstrated that protein kinase C delta inhibition down-regulated E-selectin and ICAM-1 but not VCAM-1 expression. With the use of a physiologically relevant in vitro model system, we demonstrate that protein kinase C delta plays an important role in the regulation of neutrophil adherence/migration during inflammation and identifies key steps regulated by protein kinase C delta in neutrophil-endothelial interactions. PMID- 27190305 TI - Circulating T helper and T regulatory subsets in untreated early rheumatoid arthritis and healthy control subjects. AB - The pathogenic role and frequency of T cell subtypes in early rheumatoid arthritis are still unclear. We therefore performed a comprehensive analysis of the circulating T cell subtype pattern in patients with untreated early rheumatoid arthritis compared to healthy control subjects. Peripheral blood mononuclear cells were obtained from 26 patients with untreated early rheumatoid arthritis and from with 18 age- and sex-matched healthy control subjects. T helper cell types Th0, Th1, Th2, Th17, and Th1/17 and nonclassic T helper subsets were defined by flow cytometry based on the expression of chemokine receptors CCR4, CCR6, and CXCR3. Regulatory T cells were defined by expression of CD25+ CD127low and also FOXP3 CXCR5+ cells among regulatory and nonregulatory T cells were defined as T follicular regulatory and T follicular helper cells, respectively. The phenotype of T cell subsets was confirmed by transcription factor and cytokine secretion analyses. Multivariate discriminant analysis showed that patients with untreated early rheumatoid arthritis were segregated from healthy control subjects based on the circulating T cell subset profile. Among the discriminator subsets, CCR4+CXCR3- (Th2 and Th17), CTLA4+ and FOXP3+ subsets were present in significantly higher frequencies, whereas CCR4- (Th1/Th17, CCR6+CCR4-CXCR3-, and Th1) subsets were present in lower frequencies in patients with untreated early rheumatoid arthritis compared with healthy control subjects. The proportions of Th2 and Th17 subsets associated positively with each other and negatively with the CXCR3+/interferon gamma-secreting subsets (Th1 and Th1/Th17) in patients with untreated rheumatoid arthritis. The proportions of Th2 cells increased with age in patients with untreated early rheumatoid arthritis and healthy control subjects. The dominance of circulating CCR4+CXCR3- T helper subsets (Th2 and Th17) in untreated early rheumatoid arthritis point toward a pathogenic role of these cells in early stages of the disease. PMID- 27190310 TI - Spontaneous Pulsation of Peptide Microstructures in an Abiotic Liquid System. AB - We report observations of pulsating peptide formation and depeptidization in 70% aqueous acetonitrile solutions of l-Pro-l-Phe and l-Cys, resulting in the oscillatory appearance and disappearance of solid masses of microfibers and microspheres, respectively. We monitor the concentration changes of the monomeric amino acids by high-performance liquid chromatography. The concentration of all amino acid solutions used is 1.0 mg mL(-1), due to solubility limitations in 70% aqueous acetonitrile. The nonlinear concentration changes of l-Pro, l-Phe and l Cys, and the amounts of the main peptidization products observed within our monitoring periods (for l-Pro-l-Phe, 250 h, and for l-Cys, 70 h) are typically from several to 20% of the original monomer concentrations. We follow the formation and decay of the insoluble peptides by turbidimetry. We also investigate the materials formed using scanning electron microscopy and mass spectrometry. We carry out numerical simulations on a simple model that reflects the main features of spontaneous pulsation of peptide fiber or sphere formation in this abiotic liquid system. PMID- 27190304 TI - The protease inhibitor cystatin C down-regulates the release of IL-beta and TNF alpha in lipopolysaccharide activated monocytes. AB - Human cystatin C, a member of the cysteine proteinase-inhibitory family, is produced by all nucleated cells and has important roles in regulating natural immunity. Nematode homologs to human cystatin C have been shown to have anti inflammatory effects on monocytes and to reduce colitis in mice. In Crohn's disease, pathogenic activated monocytes help drive inflammatory processes via the release of proinflammatory cytokines and chemokines. In particular, tumor necrosis factor-alpha-producing inflammatory monocytes have a central role in the intestinal inflammation in patients with Crohn's disease. We investigated the potential of human cystatin C to regulate pathogenic activated monocytes and its potential as an Immunomodulator in Crohn's disease. We found that cystatin C significantly decreased the lipopolysaccharide-stimulated release and expression of interleukin-1beta and tumor necrosis factor-alpha in monocyte and peripheral blood mononuclear cell cultures from healthy donors, whereas interleukin-6 and interleukin-8 levels were unchanged. A similar reduction of interleukin-1beta and tumor necrosis factor-alpha was also seen in peripheral blood mononuclear cell cultures from patients with Crohn's disease, and in particular, tumor necrosis factor-alpha was reduced in supernatants from lamina propria cell cultures from patients with Crohn's disease. Further investigation revealed that cystatin C was internalized by monocytes via an active endocytic process, decreased phosphorylation of the mitogen-activated protein kinase pathway extracellular signal-regulated kinase-1/2, and altered surface marker expression. The ability of cystatin C to modulate the cytokine expression of monocytes, together with its protease-inhibitory function, indicates that modulation of the local cystatin C expression could be an option in future Crohn's disease therapy. PMID- 27190311 TI - A cAMP and CREB-mediated feed-forward mechanism regulates GSK3beta in polycystic kidney disease. AB - Glycogen synthase kinase 3beta (GSK3beta), a serine/threonine protein kinase, is commonly known to be regulated at the level of its activity. However, in some diseases including polycystic kidney disease (PKD), GSK3beta expression is increased and plays a pathophysiological role. The current studies aimed to determine the mechanism for the increased GSK3beta expression in PKD and its significance to disease progression. In mouse models of PKD, increases in renal GSK3beta corresponded with increases in renal cAMP levels and disease progression. In vivo and in vitro studies revealed that GSK3beta is a cAMP responsive gene, and elevated cAMP levels, as seen in PKD, can increase GSK3beta expression. In normal mice, vasopressin signaling induced by water deprivation increased GSK3beta expression, which decreased following rehydration. Examination of the GSK3beta promoter revealed five potential binding sites for the transcription factor, cAMP response element binding protein (CREB). CREB was found to bind to GSK3beta promoter and essential for cAMP-mediated regulation of GSK3beta. Importantly, this regulation was demonstrated to be part of a feed forward loop in which cAMP through CREB regulates GSK3beta expression, and GSK3beta in turn positively regulates cAMP generation. GSK3beta or CREB inhibition reduced transepithelial fluid secretion and cyst expansion in vitro Thus, disruption at any point of this destructive cycle may be therapeutically useful to reduce cyst expansion and preserve renal function in PKD. PMID- 27190313 TI - BTG4 is a key regulator for maternal mRNA clearance during mouse early embryogenesis. PMID- 27190312 TI - Sublytic C5b-9 triggers glomerular mesangial cell apoptosis in rat Thy-1 nephritis via Gadd45 activation mediated by Egr-1 and p300-dependent ATF3 acetylation. AB - The apoptosis of glomerular mesangial cells (GMCs) is considered to be an important contributor to the initiation and development of rat Thy-1 nephritis (Thy-1N) and is accompanied by sublytic C5b-9 deposition. However, the mechanism by which sublytic C5b-9 triggers GMC apoptosis has not been elucidated. In this study, functional and histological examinations were performed on GMCs treated with sublytic C5b-9 (in vitro) and renal tissues of Thy-1N rats (in vivo). The in vitro studies found that sublytic C5b-9 could trigger GMC apoptosis through upregulating Egr-1, ATF3, and Gadd45 expression. Egr-1-mediated post transcriptional modulation of ATF3, Egr-1/ATF3-enhanced Gadd45 promoter activity, and p300-mediated ATF3 acetylation were all involved in GMC apoptosis. More importantly, the effective binding elements for Egr-1 and ATF3 to Gadd45beta/gamma promoters and the ATF3 acetylation site were identified. In vivo, silencing renal p300, Egr-1, ATF3, and Gadd45beta/gamma significantly decreased GMC apoptosis, secondary GMC proliferation, and urinary protein secretion in Thy-1N rats. Together, these findings implicate that sublytic C5b-9 induced activation of Egr-1/p300-ATF3/Gadd45 axis plays a critical role in GMC apoptosis in Thy-1N rats. PMID- 27190316 TI - A 27-Year-Old Woman With an Unusual Cause of Periprosthetic Joint Infection. PMID- 27190314 TI - Crumbs 3b promotes tight junctions in an ezrin-dependent manner in mammalian cells. AB - Crumbs 3 (CRB3) is a component of epithelial junctions, which has been implicated in apical-basal polarity, apical identity, apical stability, cell adhesion, and cell growth. CRB3 undergoes alternative splicing to yield two variants: CRB3a and CRB3b. Here, we describe novel data demonstrating that, as with previous studies on CRB3a, CRB3b also promotes the formation of tight junctions (TJs). However, significantly we demonstrate that the 4.1-ezrin-radixin-moesin-binding motif of CRB3b is required for CRB3b functionality and that ezrin binds to the FBM of CRB3b. Furthermore, we show that ezrin contributes to CRB3b functionality and the correct distribution of TJ proteins. We demonstrate that both CRB3 isoforms are required for the production of functionally mature TJs and also the localization of ezrin to the plasma membrane. Finally, we demonstrate that reduced CRB3b expression in head and neck squamous cell carcinoma (HNSCC) correlates with cytoplasmic ezrin, a biomarker for aggressive disease, and shows evidence that while CRB3a expression has no effect, low CRB3b and high cytoplasmic ezrin expression combined may be prognostic for HNSCC. PMID- 27190318 TI - A Novel Collaborative Community-Based Hepatitis B Screening and Linkage to Care Program for African Immigrants. AB - BACKGROUND: Sub-Saharan African nations have among the highest rates of chronic hepatitis B virus (HBV) infection worldwide, but little is known about HBV infection in African-born persons in the United States. METHODS: From October 2011 to July 2013, community-based HBV screenings were conducted targeting persons originating from Africa in New York City. Persons were identified as currently HBV infected (HBsAg positive) or exposed (HBcAb positive). RESULTS: Overall, 955 persons were screened for HBV; the median age was 45 years (interquartile range, 35-54 years) and 75.5% were men. Of these, 919 persons had no history of liver disease, of whom 9.6% (n = 88) had current HBV infection and 73.9% (n = 679) had exposure. In logistic regression, older age (odds ratio [OR], 0.97; 95% confidence interval [CI], .94-.99; P < .01) and female sex (OR, 0.35; 95% CI, .14-.75; P < .01) were less likely to be associated with HBV infection, whereas having a mother with hepatitis was associated with infection (OR, 18.8; 95% CI, 2.72-164.65; P < .01). HBV exposure was associated with older age (OR, 1.03; 95% CI, 1.01-1.04; P < .01), whereas female sex (OR, 0.46; 95% CI, .33-.66; P < .01) and history of blood transfusion (OR, 0.43; 95% CI, .22-.83; P = .01) were negatively associated. A patient navigator linked 97% of infected persons to care. Eleven persons were recommended for treatment, of whom 9 (82%) started therapy. Three persons were diagnosed with hepatocellular carcinoma on the first screening ultrasound. CONCLUSIONS: The high burden of HBV infection among African immigrants in the United States underscores a need for continued screening and linkage to care in this at-risk population. PMID- 27190317 TI - Mechanism of Hepatitis B Virus Persistence in Hepatocytes and Its Carcinogenic Potential. AB - Liver disease associated with persistent infection with hepatitis B virus (HBV) continues to be a major health problem of global impact. Despite the existence of an effective vaccine, at least 240 million people are chronically infected worldwide, and are at risk of developing liver cirrhosis and hepatocellular carcinoma. Although chronic HBV infection is considered the main risk factor for liver cancer development, the molecular mechanisms determining persistence of infection and long-term pathogenesis are not fully elucidated but appear to be multifactorial. Current therapeutic regimens based on the use of polymerase inhibitors can efficiently suppress viral replication but are unable to eradicate the infection. This is due both to the persistence of the HBV genome, which forms a stable minichromosome, the covalently closed circular DNA (cccDNA), in the nucleus of infected hepatocytes, as well as to the inability of the immune system to efficiently counteract chronic HBV infection. In this regard, the unique replication strategies adopted by HBV and viral protein production also appear to contribute to infection persistence by limiting the effectiveness of innate responses. The availability of improved experimental systems and molecular techniques have started to provide new information about the complex network of interactions that HBV establishes within the hepatocyte and that may contribute to disease progression and tumor development. Thus, this review will mostly focus on events involving the hepatocyte: the only target cell where HBV infection and replication take place. PMID- 27190319 TI - Virus and Host Testing to Manage Chronic Hepatitis B. AB - Chronic hepatitis B virus (HBV) infection is a major cause of cirrhosis and hepatocellular carcinoma worldwide. The past 50 years have seen rapid developments in HBV testing. Beginning from traditional serologic tests, the availability of sensitive HBV DNA assays allows a thorough understanding of the virology and natural history of chronic HBV infection. Quantification of hepatitis B surface antigen levels reflects the amount and transcriptional activities of covalently closed circular DNA in the liver and may be used to evaluate the stage of disease and guide antiviral therapy. The natural history of chronic HBV infection is also a manifestation of the interaction between the host and the virus, and recent genomic works have shed light on the host-virus relationship and may provide novel tests in the future. This review highlights recent advances in the application of HBV tests in the management of chronic hepatitis B. PMID- 27190320 TI - Hepatitis B Virus Reactivation in the Setting of Cancer Chemotherapy and Other Immunosuppressive Drug Therapy. AB - Hepatitis B virus reactivation (HBVr) is an important complication of immunosuppressive drug therapy (ISDT). It can occur with active or resolved hepatitis B virus (HBV) infection with a clinical spectrum that ranges from mild elevations in liver tests to fulminant hepatic failure. The risk of it occurring is determined by the interplay between HBV serological status, level of viremia, and the immunosuppressive potency of the drug(s) used. Reactivation is most common during treatment of hematologic malignancies but also occurs with chemotherapy for breast cancer and numerous other solid organ malignancies, organ transplant, and immune suppression for nonmalignant conditions. The expansion of new biologic treatments for malignant and nonmalignant disorders has enlarged the population at risk. Increased awareness of HBVr among healthcare providers who prescribe ISDT, adoption of routine HBV screening, and linking the results of screening to antiviral prophylaxis are needed to reduce the incidence of this potentially fatal but preventable disorder. PMID- 27190321 TI - Hepatitis B in Pregnancy. AB - Chronic hepatitis B virus (HBV) infection is estimated to affect >350 million people worldwide and represents a significant cause of morbidity and mortality related to cirrhosis and hepatocellular carcinoma. Mother-to-child transmission (MTCT) of HBV remains an important source of incident cases of HBV. Current barriers to eradication of incident HBV infections via MTCT include underutilization of immunoprophylaxis with hepatitis B vaccination and hepatitis B immune globulin in certain endemic regions as well as failure of immunoprophylaxis. PMID- 27190322 TI - Eradication Strategies for Chronic Hepatitis B Infection. AB - Chronic hepatitis B infection affects >300 million people worldwide and is a leading cause of liver failure and cancer. Current approaches to treatment for chronic hepatitis B involve suppression of hepatitis B virus (HBV) DNA with the use of nucleoside analogues. Chronic suppressive therapy rarely results in a "functional cure" or absence of detectable HBV DNA in plasma and loss of detectable hepatitis B surface antigen after cessation of therapy. The major obstacles to achieving a functional cure are the presence of covalently closed circular DNA and ineffective/exhaustive immune system. This review focuses on novel approaches to target viral life cycle and host immunity to achieve a functional cure. PMID- 27190324 TI - Risk of fracture in adults on renal replacement therapy: a Danish national cohort study. AB - BACKGROUND: Patients on dialysis treatment or living with a transplanted kidney have several risk factors for bone fracture, especially disturbances in mineral metabolism and immunosuppressive therapy. We describe the incidence of fracture in this retrospective national Danish cohort study and explore the influence of age, gender, comorbidity and prescribed medication. METHODS: By individual-level linkage between nationwide administrative registries, the risk of fracture was compared between the group of patients receiving chronic dialysis treatment and patients receiving their first renal transplant in the study period, using the Danish background population as reference group. All three groups were followed up until first fracture, emigration, death or end of study. Cox proportional hazard models with fracture as outcome were fitted to the data. RESULTS: The hazard ratio (HR) for any fracture was 3.14 [95% confidence interval (95% CI):2.97-3.31] in the dialysis group and 1.94 (95% CI: 1.72-2.18) in the renal transplanted group. The HR remained increased, but was modified by adjustment for age, gender, comorbidity and prior fracture [dialysis group: 1.85 (95% CI: 1.75 1.95); renal transplanted group: 1.82 (95% CI: 1.62-2.06)]. Prescribed diuretics, lipid-modifying agents and proton pump inhibitors also modulated the fracture risk. CONCLUSIONS: Patients on dialysis or living with a transplanted kidney have a significantly higher risk of fracture than the Danish background population. Differences in age, gender, drug use and comorbidity only partly explain this increased risk. Further studies are warranted to explore the reason for this increased fracture risk in patients on renal replacement therapy. PMID- 27190326 TI - Averting the legacy of kidney disease: focus on childhood. PMID- 27190325 TI - Resveratrol delays polycystic kidney disease progression through attenuation of nuclear factor kappaB-induced inflammation. AB - BACKGROUND: Inflammation plays an important role in polycystic kidney disease (PKD). The current study aimed to examine the efficacy of the anti-inflammatory compound resveratrol in PKD and to investigate its underlying mechanism of action. METHODS: Male Han:SPRD (Cy/+) rats with PKD were treated with 200 mg/kg/day resveratrol or vehicle by gavage for 5 weeks. Human autosomal dominant (AD) PKD cells, three-dimensional (3D) Madin-Darby canine kidney cells and zebrafish were treated with various concentrations of resveratrol or the nuclear factor kappaB (NF-kappaB) inhibitor QNZ. RESULTS: Resveratrol treatment reduced blood urea nitrogen levels and creatinine levels by 20 and 24%, respectively, and decreased two-kidney/total body weight ratio by 15% and cyst volume density by 24% in Cy/+ rats. The proliferation index and the macrophage infiltration index were reduced by 40 and 43%, respectively, in resveratrol-treated cystic kidneys. Resveratrol reduced the levels of the pro-inflammatory factors monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-alpha) and complement factor B (CFB) in Cy/+ rat kidneys in parallel with the decreased activity of NF-kappaB (p50/p65). The activation of NF-kappaB and its correlation with pro-inflammatory factor expression were confirmed in human ADPKD cells and kidney tissues. Resveratrol and QNZ inhibited the expression of MCP-1, TNF-alpha and CFB and reduced NF-kappaB activity in ADPKD cells. Moreover, NF-kappaB blockage minimized the inhibition of inflammatory factor production by resveratrol treatment. Furthermore, resveratrol or QNZ inhibited cyst formation in the 3D cyst and zebrafish models. CONCLUSIONS: The NF-kappaB signaling pathway is activated and partly responsible for inflammation in polycystic kidney tissues. Targeting inflammation through resveratrol could be a new strategy for PKD treatment in the future. PMID- 27190327 TI - Renal biopsy in patients with diabetes: a pooled meta-analysis of 48 studies. AB - Background: The utility of renal biopsy in patients with diabetes is highly debated. Diabetics with rapidly worsening renal disease are often 'clinically' labelled as having diabetic nephropathy (DN), whereas, in many cases, they are rather developing a non-diabetic renal disease (NDRD) or mixed forms (DN + NDRD). Methods: We performed a systematic search for studies on patients with diabetes with data on the frequency of DN, NDRD and mixed forms, and assessed the positive predictive values (PPVs) and odds ratios (ORs) for such diagnoses by meta analysing single-study prevalence. Possible factors explaining heterogeneity among the different diagnoses were explored by meta-regression. Results: In the 48 included studies ( n = 4876), the prevalence of DN, NDRD and mixed forms ranged from 6.5 to 94%, 3 to 82.9% and 4 to 45.5% of the overall diagnoses, respectively. IgA nephropathy was the most common NDRD (3-59%). PPVs for DN, NDRD and mixed forms were 50.1% [95% confidence interval (CI): 44.7-55.2], 36.9% (95% CI: 32.3-41.8) and 19.7% (95% CI: 16.3-23.6), respectively. The PPV when combining NDRD and mixed forms was 49.2% (95% CI: 43.8-54.5). Meta-regression identified systolic pressure, HbA1c, diabetes duration and retinopathy as factors explaining heterogeneity for NDRD, creatinine and glomerular filtration rate for mixed forms and only serum creatinine for DN. ORs of DN versus NDRD and mixed forms were 1.71 (95% CI: 1.54-1.91) and 4.1 (95% CI: 3.43-4.80), respectively. Conclusions: NDRD are highly prevalent in patients with diabetes. Clinical judgment alone can lead to wrong diagnoses and delay the establishment of adequate therapies. Risk stratification according to individual factors is needed for selecting patients who might benefit from biopsy. PMID- 27190328 TI - Sex hormones in women with kidney disease. AB - Menstrual disorders, infertility and premature menopause are common but often underrecognized phenomena among women with chronic kidney disease. Hypothalamic, rather than ovarian dysfunction, may be the cause of the abnormal reproductive milieu, which can be at least partially reversed by kidney transplantation and increased intensity of hemodialysis. Endogenous sex hormones, and specifically estradiol, appear to be renoprotective in women, although the effects of exogenous estradiol (as an oral contraceptive and postmenopausal hormone therapy) on kidney function are more controversial. Treatment with postmenopausal hormone therapy in women with end-stage kidney disease (ESKD) has been associated with improved quality of life, bone health and markers of cardiovascular risk, as well as an increased risk of arteriovenous access thrombosis. The selective estrogen receptor modulator raloxifene has been associated with both a decreased fracture risk as well as renoprotection in women with kidney disease. Young women with ESKD are more likely to die from infection or develop malignancy, suggesting an immunomodulatory role of estrogen. Whether the premature menopause commonly observed in female patients with kidney disease results in increased cardiovascular morbidity and mortality is unknown, although preliminary studies have suggested a possible therapeutic role for manipulation of the sex hormone milieu to mitigate risk in this population. Large, prospective, randomized studies examining the role of sex hormones in women with kidney disease are required to address the question. PMID- 27190330 TI - Obesity and the risk of cardiovascular and all-cause mortality in chronic kidney disease: a systematic review and meta-analysis. AB - Background: Obesity is a risk factor for cardiovascular disease and death in people without chronic kidney disease (CKD), but the effect of obesity in people with CKD is uncertain. Methods: Medline and Embase (from inception to January 2015) were searched for cohort studies measuring obesity by body mass index (BMI), waist:hip ratio (WHR) and/or waist circumference (WC) and all-cause and cardiovascular mortality or events in patients with any stage of CKD. Data were summarized using random effects models. Meta-regression was conducted to assess sources of heterogeneity. Results: Of 4065 potentially eligible citations, 165 studies ( n = 1 534 845 participants) were analyzed. In studies that found a nonlinear relationship, underweight people with CKD (3-5) on hemodialysis experienced an increased risk of death compared with those with normal weight. In transplant recipients, excess risk was observed at levels of morbid obesity (>35 kg/m 2 ). Of studies that found the relationship to be linear, a 1 kg/m 2 increase in BMI was associated with a 3 and 4% reduction in all-cause and cardiovascular mortality in patients on hemodialysis, respectively {adjusted hazard ratio [HR] 0.97 [95% confidence interval (CI) 0.96-0.98] and adjusted HR 0.96 (95% CI 0.92-1.00)}. In CKD Stages 3-5, for every 1 kg/m 2 increase in BMI there was a 1% reduction in all-cause mortality [HR 0.99 (95% CI 0.0.97-1.00)]. There was no apparent association between obesity and mortality in transplanted patients or those on peritoneal dialysis. Sparse data for WHR and WC did not allow further analyses. Conclusions: Being obese may be protective for all-cause mortality in the predialysis and hemodialysis populations, while being underweight suggests increased risk, but not in transplant recipients. PMID- 27190329 TI - Efficacy and safety of nicotinamide in haemodialysis patients: the NICOREN study. AB - Background: Nicotinamide (NAM) has been proposed as an alternative treatment to phosphate binders for hyperphosphataemia in chronic kidney disease. Methods: The NICOREN multicentre, open-label and randomized study was designed to examine non inferiority and safety of NAM when compared with sevelamer (SEV) in chronic haemodialysis patients. One hundred patients were randomized to either NAM or SEV treatment for 24 weeks. Serum biochemistry and NAM's main metabolite, N -methyl-2 pyridone-5-carboxamide (2PY), were measured to assess compliance, efficacy and safety. Results: After 24 weeks, we observed a comparable decrease in serum phosphorus in the NAM and SEV treatment arms, from 2.1 +/- 0.4 to 1.8 +/- 0.5 and 2.3 +/- 0.5 to 1.7 +/- 0.5 mM (P = not significant), respectively. The criterion for non-inferiority was, however, not met due to a more limited number of patients being included than planned. Treatment discontinuation due to adverse events was 1.6 times higher in the NAM than in the SEV group with only 55% of study completers in the NAM arm versus 90% in the SEV arm. Thrombocytopenia was observed in four NAM-treated patients. Serum 2PY levels were comparable at baseline, but increased markedly in the NAM group, but not in the SEV group, at 24 weeks (P < 0.0001). Conclusions: Thus, both drugs are equally effective in lowering serum phosphorus, but patients' tolerance of NAM was largely inferior to that of SEV. Extremely high 2PY levels may contribute to NAM's side effects. PMID- 27190331 TI - A simple care bundle for use in acute kidney injury: a propensity score-matched cohort study. AB - BACKGROUND: Consensus guidelines for acute kidney injury (AKI) have recommended prompt treatment including attention to fluid balance, drug dosing and avoidance of nephrotoxins. These simple measures can be incorporated in a care bundle to facilitate early implementation. The objective of this study was to assess the effect of compliance with the AKI care bundle (AKI-CB) on in-hospital case fatality and AKI progression. METHODS: In this larger, propensity score-matched cohort of multifactorial AKI, we examined the impact of compliance with an AKI-CB in 3717 consecutive episodes of AKI in 3518 patients between 1 August 2013 and 31 January 2015. Propensity score matching was performed to match 939 AKI events where the AKI-CB was completed with 1823 AKI events where AKI-CB was not completed. RESULTS: The AKI-CB was completed in 25.6% of patients within 24 h. The unadjusted case-fatality was higher when the AKI-CB was not completed versus when the AKI-CB was completed (24.4 versus 20.4%, P = 0.017). In multivariable analysis, AKI-CB completion within 24 h was associated with lower odds for in hospital death [odds ratio (OR): 0.76; 95% confidence interval (95% CI): 0.62 0.92]. Increasing age (OR: 1.04; 95% CI: 1.03-1.05), hospital-acquired AKI (OR: 1.28; 95% CI: 1.04-1.58), AKI stage 2 (OR: 1.91; 95% CI: 1.53-2.39) and increasing Charlson's comorbidity index (CCI) [OR: 3.31 (95% CI: 2.37-4.64) for CCI of more than 5 compared with zero] had higher odds for death, whereas AKI during elective admission was associated with lower odds for death (OR: 0.29; 95% CI: 0.16-0.52). Progression to higher AKI stages was lower when the AKI-CB was completed (4.2 versus 6.7%, P = 0.02). CONCLUSIONS: Compliance with an AKI-CB was associated with lower mortality and reduced progression of AKI to higher stages. The AKI-CB is simple and inexpensive, and could therefore be applied in all healthcare settings to improve outcomes. PMID- 27190332 TI - Fetuin-A-containing calciprotein particles in mineral trafficking and vascular disease. AB - Calcium and phosphate combine to form insoluble precipitates in both inorganic and organic materials. This property is useful biologically and has been used by numerous organisms to create hard tissues, a process referred to as biomineralisation [1]. In humans, calcium and phosphate combine to form useful crystal structures largely composed of calcium hydroxyapatite [Ca10(PO4)6(OH)2] and these are essential in the growth, maintenance and strength of parts of the skeleton and other structures like teeth. However, it remains unclear how the body achieves the exquisite specificity involved in biomineralisation. In ageing and disease, these pathways are perturbed, resulting in ectopic calcium crystal deposition impairing tissue function and, interestingly, frequently accompanied by simultaneous loss of mineral from sites where it is useful (e.g. bone). One paradigm for this maladaptive situation is renal failure; a situation that we know is associated with vascular stiffening and calcification, along with mineral loss from the skeleton. Mineral trafficking is a loose term used to describe the movements of calcium salts around the body, and new insights into these pathways may explain some of the problems of previous models of bone mineral disease in renal failure and point to potential future therapeutic strategies. PMID- 27190333 TI - APOL1-associated glomerular disease among African-American children: a collaboration of the Chronic Kidney Disease in Children (CKiD) and Nephrotic Syndrome Study Network (NEPTUNE) cohorts. AB - Background: Individuals of African ancestry harboring two variant alleles within apolipoprotein L1 ( APOL1 ) are classified with a high-risk (HR) genotype. Adults with an HR genotype have increased risk of focal segmental glomerulosclerosis and chronic kidney disease compared with those with a low-risk (LR) genotype (0 or 1 variants). The role of APOL1 risk genotypes in children with glomerular disease is less well known. Methods: This study characterized 104 African-American children with a glomerular disease by APOL1 genotype in two cohorts: the Chronic Kidney Disease in Children (CKiD) and Nephrotic Syndrome Study Network (NEPTUNE). Results: Among these subjects, 46% had an HR genotype with a similar age at cohort enrollment. For APOL1 HR children, the median age of disease onset was older (CKiD: 4.5 versus 11.5 years for LR versus HR; NEPTUNE: 11 versus 14 years for LR versus HR, respectively) and preterm birth was more common [CKiD: 27 versus 4%; NEPTUNE: 26 versus 12%; combined odds ratio 4.6 (95% confidence interval: 1.4, 15.5)]. Within studies, HR children had lower initial estimated glomerular filtration rate (eGFR) (CKiD: 53 versus 69 mL/min/1.73 m 2 ; NEPTUNE: 74 versus 94 mL/min/1.73 m 2 ). Longitudinal eGFR decline was faster among HR children versus LR (CKiD: -18 versus -8% per year; NEPTUNE: -13 versus -3% per year). Conclusions: Children with an HR genotype in CKiD and NEPTUNE seem to have a more aggressive form of glomerular disease, in part due to a higher prevalence of focal segmental glomerulosclerosis. These consistent findings across independent cohorts suggest a common natural history for children with APOL1 associated glomerular disease. Further study is needed to determine the generalizability of these findings. PMID- 27190334 TI - Outcomes in patients with chronic kidney disease not on dialysis receiving extended dosing regimens of darbepoetin alfa: long-term results of the EXTEND observational cohort study. AB - BACKGROUND: Extended dosing of the erythropoiesis-stimulating agent (ESA) darbepoetin alfa (DA) once biweekly or monthly reduces anaemia treatment burden. This observational study assessed outcomes and dosing patterns in patients with chronic kidney disease not on dialysis (CKD-NoD) commencing extended dosing of DA. METHODS: Adult CKD-NoD patients starting extended dosing of DA in Europe or Australia in June 2006 or later were followed up until December 2012. Outcomes included haemoglobin (Hb) concentration, ESA dosing, mortality rates and receipt of dialysis and renal transplantation. Subgroup analyses were conducted for selected outcomes. RESULTS: Of 6035 enrolled subjects, 5723 (94.8%) met analysis criteria; 1795 (29.7%) received dialysis and 238 (3.9%) underwent renal transplantation. Mean (standard deviation) Hb concentration at commencement of extended dosing was 11.0 (1.5) g/dL. Mean [95% confidence interval (CI)] Hb 12 months after commencement of extended dosing (primary outcome) was 11.6 g/dL (11.5, 11.6) overall and was similar across countries, with no differences between subjects previously treated with an ESA versus ESA-naive subjects, subjects with versus without prior renal transplant or diabetics versus non diabetics. Weekly ESA dose gradually decreased following commencement of extended DA dosing and was similar across subgroups. The decrease in weekly DA dose was accompanied by an increase in the proportion of patients receiving iron therapy. Hb concentrations declined following changes in ESA labels and treatment guidelines. The mortality rate (95% CI) was 7.06 (6.68, 7.46) deaths per 100 years of follow-up. Subjects alive at study end had stable Hb concentrations in the preceding year, while those who died had lower and declining Hb concentrations in their last year. CONCLUSIONS: Long-term, extended dosing of DA maintained Hb concentrations in patients already treated with an ESA and corrected and maintained Hb in ESA-naive patients. PMID- 27190335 TI - Genotypic and phenotypic predictors of inflammation in patients with chronic kidney disease. AB - BACKGROUND: In complex diseases such as chronic kidney disease (CKD), the risk of clinical complications is determined by interactions between phenotypic and genotypic factors. However, clinical epidemiological studies rarely attempt to analyse the combined effect of large numbers of phenotype and genotype features. We have recently shown that the relaxed linear separability (RLS) model of feature selection can address such complex issues. Here, it is applied to identify risk factors for inflammation in CKD. METHODS: The RLS model was applied in 225 CKD stage 5 patients sampled in conjunction with dialysis initiation. Fifty-seven anthropometric or biochemical measurements and 79 genetic polymorphisms were entered into the model. The model was asked to identify phenotypes and genotypes that, when combined, could separate inflamed from non inflamed patients. Inflammation was defined as a high-sensitivity C-reactive protein concentration above the median (5 mg/L). RESULTS: Among the 60 genotypic and phenotypic features predicting inflammation, 31 were genetic. Among the 10 strongest predictors of inflammation, 8 were single nucleotide polymorphisms located in the NAMPT, CIITA, BMP2 and PIK3CB genes, whereas fibrinogen and bone mineral density were the only phenotypic biomarkers. CONCLUSION: These results indicate a larger involvement of hereditary factors in inflammation than might have been expected and suggest that inclusion of genotype features in risk assessment studies is critical. The RLS model demonstrates that inflammation in CKD is determined by an extensive panel of factors and may prove to be a suitable tool that could enable a much-needed multifactorial approach as opposed to the commonly utilized single-factor analysis. PMID- 27190336 TI - Clinical safety and performance of VIVIA: a novel home hemodialysis system. AB - Background: The VIVIA Hemodialysis System (Baxter Healthcare Corporation, Deerfield, IL, USA) was designed for patient use at home to reduce the burden of treatment and improve patient safety. It has unique features including extended use of the dialyzer and blood set through in situ hot-water disinfection between treatments; generation of on-line infusible-quality dialysate for automated priming, rinseback and hemodynamic support during hypotension and a fully integrated access disconnect sensor. Methods: The safety and performance of VIVIA were assessed in two clinical studies. A first-in-man study was a prospective, single-arm study that involved 22 prevalent hemodialysis (HD) patients who were treated for ~4 h, four times a week, for 10 weeks. A second clinical study was a prospective, single-arm study (6-8 h of dialysis treatment at night three times a week) that involved 17 prevalent patients treated for 6 weeks. Results: There were 1114 treatments from the two studies (first-in-man study, 816; extended duration study, 298). Adverse events (AEs) were similar in the two studies to those expected for prevalent HD patients. No deaths and no device-related serious AEs occurred. Adequacy of dialysis ( Kt / V ) urea in both clinical trials was well above the clinical guidelines. VIVIA performed ultrafiltration accurately as prescribed in the two studies. The majority of patients achieved 10 or more uses of the dialyzer. Endotoxin levels and bacterial dialysate sampling met infusible quality dialysate standards. Conclusion: These results confirm the safety and expected performance of VIVIA. PMID- 27190337 TI - Intestinal metabolites, chronic kidney disease and renal transplantation: Enigma Variations? PMID- 27190340 TI - KDIGO-based acute kidney injury criteria operate differently in hospitals and the community-findings from a large population cohort. AB - BACKGROUND: Early recognition of acute kidney injury (AKI) is important. It frequently develops first in the community. KDIGO-based AKI e-alert criteria may help clinicians recognize AKI in hospitals, but their suitability for application in the community is unknown. METHODS: In a large renal cohort (n = 50 835) in one UK health authority, we applied the NHS England AKI 'e-alert' criteria to identify and follow three AKI groups: hospital-acquired AKI (HA-AKI), community acquired AKI admitted to hospital within 7 days (CAA-AKI) and community-acquired AKI not admitted within 7 days (CANA-AKI). We assessed how AKI criteria operated in each group, based on prior blood tests (number and time lag). We compared 30 day, 1- and 5-year mortality, 90-day renal recovery and chronic renal replacement therapy (RRT). RESULTS: In total, 4550 patients met AKI e-alert criteria, 61.1% (2779/4550) with HA-AKI, 22.9% (1042/4550) with CAA-AKI and 16.0% (729/4550) with CANA-AKI. The median number of days since last blood test differed between groups (1, 52 and 69 days, respectively). Thirty-day mortality was similar for HA-AKI and CAA-AKI, but significantly lower for CANA-AKI (24.2, 20.2 and 2.6%, respectively). Five-year mortality was high in all groups, but followed a similar pattern (67.1, 64.7 and 46.2%). Differences in 5-year mortality among those not admitted could be explained by adjusting for comorbidities and restricting to 30 day survivors (hazard ratio 0.91, 95% confidence interval 0.80-1.04, versus hospital AKI). Those with CANA-AKI (versus CAA-AKI) had greater non-recovery at 90 days (11.8 versus 3.5%, P < 0.001) and chronic RRT at 5 years (3.7 versus 1.2%, P < 0.001). CONCLUSIONS: KDIGO-based AKI criteria operate differently in hospitals and in the community. Some patients may not require immediate admission but are at substantial risk of a poor long-term outcome. PMID- 27190341 TI - Skeletal fractures in patients on renal replacement therapy: how large still is the knowledge gap? PMID- 27190343 TI - Central blood pressures in early chronic kidney disease: an analysis of CARTaGENE. AB - Background: Vascular stiffness and advanced chronic kidney disease (CKD) are strong determinants of higher central blood pressure (BP) and are associated with high cardiovascular morbidity and mortality. Whether mild-to-moderate CKD is associated with higher central BP independently of other comorbid conditions remains uncertain. Methods: We evaluated the central hemodynamic profile [central systolic BP, central pulse pressure (PP), augmentation index, PP amplification, augmented pressure] of Stage 3 CKD patients and compared it with participants with estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m 2 in the CARTaGENE populational cohort through propensity score matching and multivariate regression analyses. Results: Of the 20 004 participants, 13 114 had valid pulse wave analysis and eGFRs >30 mL/min/1.73 m 2 , of which 515 had Stage 3 CKD. These 515 patients had significantly higher peripheral systolic BP (127 +/- 16 versus 125 +/- 15 mmHg, P = 0.01) and central PP (43.0 +/- 11.4 versus 39.7 +/- 10.0 mmHg, P <0.001) than the control group (eGFR >60 mL/min/1.73 m 2 ). Propensity score matching allowed the creation of 500 pairs with similar clinical characteristics. In this matched cohort, central BPs were similar in Stage 3 CKD patients compared with controls (central PP 42.9 +/- 11.3 versus 43.7 +/- 11.3 mmHg, P = 0.3). Multivariate analysis using data from all patients also found that the higher central hemodynamic readings found in Stage 3 CKD patients disappeared after adjusting for comorbid conditions. In a subset of 609 participants in whom albuminuria levels were measured, urine albumin excretion was not independently associated with higher central hemodynamic indices. Conclusion: In this large cohort from the general population, early CKD and albuminuria was not independently associated with detrimental central hemodynamic parameters. PMID- 27190342 TI - Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use and cardiovascular outcomes in patients initiating peritoneal dialysis. AB - Background: Data on the effectiveness of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in reducing cardiovascular (CV) risk in patients undergoing peritoneal dialysis (PD) are limited. We investigated the association between ACEI/ARB use and CV outcomes in patients initiating PD. Methods: In this observational cohort study, we identified from the United States Renal Data System all adult patients who initiated PD from 2007 to 2011 and participated in Medicare Part D, a federal prescription drug benefits program, for the first 90 days of dialysis. Patients who filled a prescription for an ACEI or ARB in those 90 days were considered users. We applied Cox regression to an inverse probability of treatment weighted cohort to estimate the hazard ratios (HRs) for the combined outcome of death, ischemic stroke or myocardial infarction (MI) and each outcome individually. Results: Among 4879 patients, 2063 (42%) used an ACEI/ARB. Patients were followed up for a median of 1.2 years. We recorded 1771 events, for a composite rate of 25 events per 100 person-years. ACEI/ARB use (versus nonuse) was associated with a reduced risk of the composite outcome {HR 0.84 [95% confidence interval (CI) 0.76-0.93]}, all cause mortality [HR 0.83 (95% CI 0.75-0.92)] and CV death [HR 0.74 (95% CI 0.63 0.87)], but not MI [HR 0.88 (95% CI 0.69-1.12)] or ischemic stroke [HR 1.06 (95% CI 0.79-1.43)]. Results were similar in as-treated analyses. In a subgroup analysis, we did not find any effect modification by residual renal function. Conclusions: ACEI/ARB use is common in patients initiating PD and is associated with a lower risk of fatal CV outcomes. PMID- 27190344 TI - Cum grano salis. PMID- 27190346 TI - NUP107 mutations in children with steroid-resistant nephrotic syndrome. AB - Background: NUP107 is a novel gene associated with autosomal recessive steroid resistant nephrotic syndrome (SRNS) with focal segmental glomerulosclerosis (FSGS) in children. The frequency of NUP107 mutations in children with SR-FSGS remains unknown. Methods: Nine families with two siblings affected by childhood onset SRNS or proteinuria were recruited. FSGS was confirmed by a kidney biopsy in at least one affected sibling in all families. Additionally, 69 sporadic pediatric cases with biopsy-proven SR-FSGS who had not responded to any treatment were included. All coding exons with flanking introns of the NUP107 gene were amplified using polymerase chain reaction and directly sequenced. Results: Biallelic NUP107 mutations were detected in four pairs (44.4%) of siblings from the familial cases and three (4.3%) sporadic cases. All affected patients harbored the p.Asp831Ala mutation in one allele and a truncating or abnormal splicing mutation in the other allele. NUP107 mutation-positive patients showed an earlier onset age (39.4 +/- 13.1 versus 76.8 +/- 50.0 months, P= 0.027) and more rapid progression to end-stage renal disease (at the ages of 58.9 +/- 23.4 versus 123.1 +/- 62.7 months, P < 0.001) compared with mutation-negative patients. None of the eight mutation-positive cases, who underwent kidney transplantation, showed recurrence of FSGS in the graft kidney, while 35.3% of mutation-negative cases showed recurrence of FSGS. Conclusions: An unexpectedly high incidence of NUP107 mutations was observed in Korean children with SR-FSGS. Initial genetic screening of children with SR-FSGS should include the NUP107 gene, at least in Korea. Further studies are necessary to determine the incidences of NUP107 mutations in other countries. PMID- 27190347 TI - Effect of a sustained difference in hemodialytic clearance on the plasma levels of p-cresol sulfate and indoxyl sulfate. AB - BACKGROUND: The protein-bound solutes p-cresol sulfate (PCS) and indoxyl sulfate (IS) accumulate to high plasma levels in renal failure and have been associated with adverse events. The clearance of these bound solutes can be altered independently of the urea clearance by changing the dialysate flow and dialyzer size. This study tested whether a sustained difference in clearance would change the plasma levels of PCS and IS. METHODS: Fourteen patients on thrice-weekly nocturnal hemodialysis completed a crossover study of two periods designed to achieve widely different bound solute clearances. We compared the changes in pre dialysis plasma PCS and IS levels from baseline over the course of the two periods. RESULTS: The high-clearance period provided much higher PCS and IS clearances than the low-clearance period (PCS: 23 +/- 4 mL/min versus 12 +/- 3 mL/min, P < 0.001; IS: 30 +/- 5 mL/min versus 17 +/- 4 mL/min, P < 0.001). Despite the large difference in clearance, the high-clearance period did not have a different effect on PCS levels than the low-clearance period [from baseline, high: +11% (-5, +37) versus low: -8% (-18, +32), (median, 25th, 75th percentile), P = 0.50]. In contrast, the high-clearance period significantly lowered IS levels compared with the low-clearance period [from baseline, high: -4% (-17, +1) versus low: +22% (+14, +31), P < 0.001). The amount of PCS removed in the dialysate was significantly greater at the end of the high-clearance period [269 (206, 312) versus 199 (111, 232) mg per treatment, P < 0.001], while the amount of IS removed was not different [140 (87, 196) versus 116 (89, 170) mg per treatment, P = 0.15]. CONCLUSIONS: These findings suggest that an increase in PCS generation prevents plasma levels from falling when the dialytic clearance is increased. Suppression of solute generation may be required to reduce plasma PCS levels in dialysis patients. PMID- 27190345 TI - Advances and unmet needs in genetic, basic and clinical science in Alport syndrome: report from the 2015 International Workshop on Alport Syndrome. AB - Alport syndrome (AS) is a genetic disease characterized by haematuric glomerulopathy variably associated with hearing loss and anterior lenticonus. It is caused by mutations in the COL4A3, COL4A4 or COL4A5 genes encoding the alpha3alpha4alpha5(IV) collagen heterotrimer. AS is rare, but it accounts for >1% of patients receiving renal replacement therapy. Angiotensin-converting enzyme inhibition slows, but does not stop, the progression to renal failure; therefore, there is an urgent requirement to expand and intensify research towards discovering new therapeutic targets and new therapies. The 2015 International Workshop on Alport Syndrome targeted unmet needs in basic science, genetics and diagnosis, clinical research and current clinical care. In three intensive days, more than 100 international experts including physicians, geneticists, researchers from academia and industry, and patient representatives from all over the world participated in panel discussions and breakout groups. This report summarizes the most important priority areas including (i) understanding the crucial role of podocyte protection and regeneration, (ii) targeting mutations by new molecular techniques for new animal models and potential gene therapy, (iii) creating optimal interaction between nephrologists and geneticists for early diagnosis, (iv) establishing standards for mutation screening and databases, (v) improving widespread accessibility to current standards of clinical care, (vi) improving collaboration with the pharmaceutical/biotech industry to investigate new therapies, (vii) research in hearing loss as a huge unmet need in Alport patients and (viii) the need to evaluate the risk and benefit of novel (including 'repurposing') therapies on an international basis. PMID- 27190348 TI - Validation of cystatin C-based equations for evaluating residual renal function in patients on continuous ambulatory peritoneal dialysis. AB - Background: Residual renal function needs to be assessed frequently in patients on continuous ambulatory peritoneal dialysis (CAPD). A commonly used method is to measure creatinine (Cr) and urea clearance in urine collected over 24 h, but collection can be cumbersome and difficult to manage. A faster, simpler alternative is to measure levels of cystatin C (CysC) in serum, but the accuracy and reliability of this method is controversial. Our study aims to validate published CysC-based equations for estimating residual renal function in patients on CAPD. Methods: Residual renal function was measured by calculating average clearance of urea and Cr in 24-h urine as well as by applying CysC- or Cr-based equations published by Hoek and Yang. We then compared the performance of the equations against the 24-h urine results. Results: In our sample of 255 patients ages 47.9 +/- 15.6 years, the serum CysC level was 6.43 +/- 1.13 mg/L. Serum CysC level was not significantly associated with age, gender, height, weight, body mass index, hemoglobin, intact parathyroid hormone, normalized protein catabolic rate or the presence of diabetes. In contrast, serum CysC levels did correlate with peritoneal clearance of CysC and with levels of prealbumin and high sensitivity C-reactive protein. Residual renal function was 2.56 +/- 2.07 mL/min/1.73 m 2 based on 24-h urine sampling, compared with estimates (mL/min/1.73 m 2 ) of 2.98 +/- 0.66 for Hoek's equation, 2.03 +/- 0.97 for Yang's CysC-based equation and 2.70 +/- 1.30 for Yang's Cr-based equation. Accuracies within 30%/50% of measured residual renal function for the three equations were 29.02/48.24, 34.90/56.86 and 31.37/54.90. Conclusion: The three equations for estimating residual renal function showed similar limits of agreement and differed significantly from the measured value. Published CysC-based equations do not appear to be particularly reliable for patients on CAPD. Further development and validation of CysC-based equations should take into account peritoneal clearance of CysC and other relevant factors. PMID- 27190351 TI - Midkine, a heparin-binding growth factor, and its roles in atherogenesis and inflammatory kidney diseases. AB - The heparin-binding protein midkine is a potent growth factor with emerging roles in numerous inflammatory diseases. Beyond its characterization in embryogenesis and organ development, ample insights into its function have been collected from experimental disease models using knockout animals or knockdown intervention strategies. Here a comprehensive overview on midkine and its functions in atherogenesis and kidney diseases is provided. Molecular clues to key signalling pathways (Akt, ERK, HIF1alpha) and key events in atherosclerotic vessels link midkine expression with vascular smooth muscle proliferation and (neo)angiogenesis. In acute and chronic kidney diseases, midkine expression is upregulated in tubular as well as endothelial cells. Experimental disease models that mimic diabetic nephropathy and/or immunologic glomerular damage indicate dichotomous midkine activities, with cytoprotective as well as injurious effects. This review also pinpoints the commonalities of the disease models. An understanding of the underlying molecular events will be required in order to design a targeted intervention into cardiovascular or renal diseases as well as inflammatory processes. PMID- 27190350 TI - Erythropoiesis-stimulating agent dosing, haemoglobin and ferritin levels in UK haemodialysis patients 2005-13. AB - Background: Erythropoiesis-stimulating agents (ESAs) with intravenous iron supplementation are the main treatment for anaemia in patients with chronic kidney disease. Although observational studies suggest better outcomes for patients who achieve higher haemoglobin (Hb) levels, randomized controlled trials comparing higher and lower Hb targets have led to safety concerns over higher targets and to changes in treatment guidelines. Methods: Quarterly data from 2005 to 2013 were obtained on 28 936 haemodialysis patients from the UK Renal Registry. We examined trends in ESA use and average dose, Hb and ferritin values over time and Hb according to the UK Renal Association guideline range. Results: The average ESA dose declined over time, with sharper decreases of epoetin seen towards the end of 2006 and from 2009. Average Hb for patients on ESAs was 114.1 g/L [95% confidence interval (CI) 113.7, 114.6] in the first quarter of 2005, which decreased to 109.6 g/L (95% CI 109.3, 109.9) by the end of 2013. Average serum ferritin was 353 ug/L (95% CI 345, 360) at the start of 2005, increasing to 386 ug/L (95% CI 380, 392) in the final quarter of 2013. The percentage of patients with Hb in the range of 100-120 g/L increased from 46.1 at the start of 2005 to 57.6 at the end of 2013. Conclusions: Anaemia management patterns for haemodialysis patients changed in the UK between 2005 and 2013. These patterns most likely reflect clinician response to emerging trial evidence and practice guidelines. Registries play an important role in continued observation of anaemia management and will monitor further changes as new evidence on optimal care emerges. PMID- 27190349 TI - Determining the research priorities for patients with chronic kidney disease not on dialysis. AB - Background: The importance of engaging key stakeholders, and patients in particular, in determining research priorities has been recognized. We sought to identify the top 10 research priorities for patients with non-dialysis chronic kidney disease (CKD), their caregivers, and the clinicians and policy-makers involved in their care. Methods: We used the four-step James Lind Alliance process to establish the top 10 research priorities. A national survey of patients with non-dialysis CKD (estimated glomerular filtration rate <45 mL/min/1.73 m 2 ), their caregivers, and the clinicians and policy-makers involved in their care was conducted to identify research uncertainties. A Steering Group of patients, caregivers, clinicians and researchers combined and reduced these uncertainties to 30 through a series of iterations. Finally, a workshop with participants from across Canada (12 patients, 6 caregivers, 3 physicians, 2 nurses, 1 pharmacist and 1 policy-maker) was held to determine the top 10 research priorities, using a nominal group technique. Results: Overall, 439 individuals responded to the survey and identified 1811 uncertainties, from which the steering group determined the top 30 uncertainties to be considered at the workshop. The top 10 research uncertainties prioritized at the workshop included questions about treatments to prevent progression of kidney disease (including diet) and to treat symptoms of CKD, provider- and patient-targeted strategies for managing CKD, the impact of lifestyle on disease progression, harmful effects of medications on disease progression, optimal strategies for treatment of cardiovascular disease in CKD and for early identification of kidney disease, and strategies for equitable access to care for patients with CKD. Conclusions: We identified the top 10 research priorities for patients with CKD that can be used to guide researchers, as well as inform funders of health-care research. PMID- 27190352 TI - Reaccumulation of globotriaosylceramide in podocytes after agalsidase dose reduction in young Fabry patients. AB - Background: Agalsidase-alpha 0.2 mg/kg every other week (eow) and agalsidase-beta 1.0 mg/kg/eow are licensed in Europe as equipotent treatment of the alpha galactosidase deficiency in Fabry disease. This case series describes the effects of agalsidase dose adjustments in serial kidney biopsies in switch patients. Methods: All treatment-naive patients with classical Fabry disease in our centre started on agalsidase-beta 1.0 mg/kg/eow and subsequently switched to agalsidase alpha 0.2 mg/kg/eow were included ( n = 3). The median age at enzyme replacement therapy start was 11 (range 7-18) years. Kidney biopsies were performed at baseline, after 5 years of agalsidase-beta 1.0 mg/kg/eow and after 3 subsequent years of agalsidase-alpha 0.2 mg/kg/eow. One patient was re-biopsied 2 years after reswitch to agalsidase-beta 1.0 mg/kg/eow. The scoring system of the International Scoring Group of Fabry Nephropathy was used. Results: The patients completely cleared globotriaosylceramide (GL3) from mesangial and endothelial cells and partly cleared podocytes on agalsidase-beta 1.0 mg/kg/eow. Reaccumulation of GL3 in podocytes, but not in the mesangium or endothelium, occurred after 3 years of agalsidase-alpha 0.2 mg/kg/eow. Subsequent reduction of podocyte GL3 was observed in the single patient rebiopsied 2 years after reswitch to agalsidase-beta 1.0 mg/kg/eow. Conclusion: Partial clearance, reaccumulation and renewed partial clearance of podocyte GL3 deposits in serial kidney biopsies over 8-10 years were seen in parallel with agalsidase dose adjustments. Repeated kidney biopsies may impact therapeutic choices in Fabry disease. PMID- 27190353 TI - Effect of resveratrol on progression of polycystic kidney disease: a case of cautious optimism. PMID- 27190354 TI - Renal effects of novel antiretroviral drugs. AB - Chronic kidney disease (CKD) is a critical comorbidity for patients living with HIV, with an estimated prevalence between 2.4 and 17%. Such patients are increasingly affected by diseases associated with ageing, including cardiovascular disease and CKD, and the prevalence of risk factors such as smoking and dyslipidaemia is increased in this population. Proteinuria is also now recognized as a common finding in individuals living with HIV. While combination antiretroviral (ARV) treatments reduce CKD in the HIV-infected population overall, some ARV drugs have been shown to be nephrotoxic and associated with worsening renal function. Over the last few years, several highly efficacious new ARV agents have been introduced. This brief review will look at the novel agents dolutegravir, raltegravir, elvitegravir, cobicistat, tenofovir alafenamide fumarate and atazanavir, all of which have been licensed relatively recently, and describe issues relevant to renal function, creatinine handling and potential nephrotoxicity. Given the prevalence of CKD, the wide range of possible interactions between HIV, ARV therapy, CKD and its treatments, nephrologists need to be aware of these newer agents and their possible effect on kidneys. PMID- 27190355 TI - Tolvaptan suppresses monocyte chemotactic protein-1 excretion in autosomal dominant polycystic kidney disease. AB - Background: Autosomal-dominant polycystic kidney disease (ADPKD) is characterized by multitudes of expanding renal cysts associated with mononuclear interstitial infiltrates. Monocyte chemotactic protein-1 is produced in the kidneys and excreted in the urine (uMCP1) of these patients in increased amounts. In the TEMPO 3:4 trial, tolvaptan slowed the rate of increase in total kidney volume (TKV) and the rate of decline in estimated glomerular filtration rate (eGFR). In a sub-analysis, we determined whether tolvaptan administration for up to 3 years changed the urinary excretion of MCP-1 referenced to creatinine in 869 treated subjects compared with 438 placebo subjects. Methods: Treatment group differences of uMCP1 at 0.75, 12, 24 and 36 months were evaluated by ANCOVA with factor of treatment and covariate baseline. Results: At baseline, mean uMCP1 was 429 +/- 224 pg/mg in the tolvaptan and 434 +/- 233 pg/mg in the placebo groups, ~4-fold greater than normal. Log uMCP1 associated positively with log TKV ( r = 0.2645, P < 0.0001) and negatively with eGFR ( r = -0.1555 P < 0.0001) and fasting urine osmolality ( r = -0.1933, P < 0.0001). Tolvaptan reduced uMCP1 13.8 +/- 4.4% (P < 0.0001) below placebo-treated subjects at 24 months and 14.4 +/- 3.7% (P < 0.0001) at 36 months, and to the same extent in females and males. The effect of tolvaptan on uMCP1 excretion at 36 months extended across CKD Stage 1 (11.1 +/- 6.4%, P = 0.0595), CKD 2 (13.9 +/- 5.4%, P = 0.0050) and CKD 3 (21.4 +/- 8.0%, P = 0.0020). Conclusion: Tolvaptan, administered for 3 years to patients with ADPKD, caused a sustained reduction in the urinary excretion of MCP-1 relative to placebo. PMID- 27190357 TI - Moderator's view: Cyclophosphamide in lupus nephritis. AB - Mycophenolate mofetil was recently accepted as the effective induction treatment of lupus nephritis, with the potential to replace cyclophosphamide or at least expand our therapeutic armamentarium in patients with this lifelong disease often requiring repeated induction treatment of its relapses. Compared with cyclophosphamide, mycophenolate may be more effective in black patients, and the risk of gonadotoxicity may be significantly lower in mycophenolate-treated subjects. However, experience with mycophenolate in severe lupus nephritis is still limited and we also have insufficient data on the long-term outcome of mycophenolate-treated patients. Treatment with mycophenolate is more expensive than with cyclophosphamide, which may limit its use, especially in low- and middle-income countries. The efficacy of mycophenolate mofetil may be more dependent on the patient's compliance compared with intravenous cyclophosphamide pulses. Low-dose cyclophosphamide remains an effective and relatively safe induction treatment of active lupus nephritis, but to decrease its cumulative toxicity, repeated exposure to cyclophosphamide in relapsing patients should be (if possible) avoided. PMID- 27190358 TI - Con: Cyclophosphamide for the treatment of lupus nephritis. AB - Kidney involvement is a major determinant for morbidity and mortality in patients with systemic lupus erythematosus. The treatment target of lupus renal disease is to induce and maintain remission and to minimize disease or treatment-related comorbidities. Cyclophosphamide (CYC), in conjunction with glucocorticoids, has conventionally been used for the initial treatment of lupus nephritis. However, the major concerns of CYC are its toxicities, such as infertility, urotoxicity and oncogenicity, which are particularly relevant in women of childbearing age. As a result, maintenance therapy of lupus nephritis with an extended course of CYC pulses has largely been replaced by other immunosuppressive agents such as mycophenolate mofetil (MMF) and azathioprine. Recent randomized controlled trials have demonstrated non-inferiority of MMF to pulse CYC as induction therapy of lupus nephritis. Although MMF as induction-maintenance therapy has been increasingly used in lupus nephritis, its efficacy in the long-term preservation of renal function remains to be elucidated. MMF is not necessarily less toxic than CYC. Meta-analyses of clinical trials show similar incidence of infective complications and gastrointestinal adverse events in both MMF- and CYC-based regimens. However, considering the reduction in gonadal toxicity and the risk of oncogenicity, MMF may be used as first-line therapy of lupus nephritis. Tacrolimus (TAC) has recently been shown to be equivalent to either MMF or CYC for inducing remission of lupus nephritis and may be considered as another non CYC alternative. Combined low-dose MMF and TAC appears to be more effective than CYC pulses in Chinese patients with lupus nephritis and has the potential to replace the more toxic CYC regimens in high-risk patients. Currently, CYC still plays an important role in the management of lupus nephritis patients with impaired or rapidly deteriorating renal function, crescentic glomerulonephritis or as salvage therapy for recalcitrant disease. PMID- 27190359 TI - Pro: Cyclophosphamide in lupus nephritis. AB - Based on efficacy and toxicity considerations, both low-dose pulse cyclophosphamide as part of the Euro-Lupus Nephritis protocol and mycophenolate mofetil (MMF) with corticosteroids may be considered for induction of remission in patients with proliferative lupus nephritis. The long-term follow-up data available for low-dose pulse cyclophosphamide, the fact that compliance is guaranteed with this regimen and economic issues all favour the Euro-Lupus regimen in this author's opinion. For maintenance treatment, either azathioprine (AZA) or MMF may be used; AZA is preferred in case pregnancy is planned, while MMF is preferred when the disease relapses during use of AZA and, possibly, after successful induction of remission with MMF. PMID- 27190360 TI - The effect of rituximab dose on infectious complications in ABO-incompatible kidney transplantation. AB - BACKGROUND: Rituximab (RIT) improves the outcomes of ABO-incompatible (ABOi) kidney transplantation (KT), but it has been associated with infectious complications. The aim of this study was to investigate infectious complications according to the dose of RIT in ABOi KT. METHODS: We analyzed 213 recipients [118 ABO-compatible (ABOc) KT and 95 ABOi KT] who underwent living donor KT between 2010 and 2014. ABOi KT patients were categorized by RIT dose: standard RIT (375 mg/m(2), n = 76) versus reduced RIT (200 mg, n = 19). All patients received basiliximab and maintained on triple immunosuppression consisting of tacrolimus, prednisone and mycophenolate mofetil. Infectious complications and post transplant outcomes were analyzed for 1 year following KT. RESULTS: The rates of overall infectious complications among the three groups were comparable (22.9% in ABOc KT, 38.2% in standard RIT and 26.3% in reduced RIT, P = 0.069). In the standard RIT group, hepatitis B virus reactivation occurred in three recipients (3.9%) with hepatitis B surface antigen[-]/anti-hepatitis B core antibody[+]. Three cases (3.9%) of Pneumocystis jirovecii pneumonia occurred in the standard RIT group. Serious infections developed in 13 of the ABOc KT (11.0%), 20 from the standard RIT group (26.3%) and 2 from the reduced RIT group (10.5%, P = 0.015). Standard-dose RIT was found to be an independent risk factor for serious infections [hazard ratio: 2.59 (95% confidence interval: 1.33-5.07), P = 0.005]. There were no significant differences in rejection, renal function, graft survival and patient survival between standard and reduced RIT groups. CONCLUSIONS: Standard RIT increased the risk of serious infection when compared with reduced-dose RIT. Reduced-dose RIT might be sufficient for ABOi KT without increasing the risk of serious infection. PMID- 27190356 TI - The effect of frequent hemodialysis on self-reported sleep quality: Frequent Hemodialysis Network Trials. AB - BACKGROUND: Many patients who receive maintenance hemodialysis experience poor sleep. Uncontrolled studies suggest frequent hemodialysis improves sleep quality, which is a strong motivation for some patients to undertake the treatment. We studied the effects of frequent in-center ('daily') and nocturnal home hemodialysis on self-reported sleep quality in two randomized trials. METHODS: Participants were randomly assigned to frequent (six times per week) or conventional (three times per week) hemodialysis in the Frequent Hemodialysis Network Daily (n = 245) and Nocturnal (n = 87) Trials. We used the Medical Outcomes Study Sleep Problems Index II (SPI II), a validated and reliable instrument in patients with end-stage renal disease, to measure self-reported sleep quality. The SPI II is scored from 0-100, with a higher value indicating poorer quality of sleep. A mean relative decline in SPI II would suggest improved sleep quality. The primary sleep outcome was the change in the SPI II score over 12 months. RESULTS: In the Daily Trial, after adjustment for baseline SPI II, subjects randomized to frequent as compared with conventional in-center hemodialysis experienced a 4.2 [95% confidence interval (CI) 0.4-8.0] point adjusted mean relative decline in SPI II at 4 months and a 2.6 (95% CI -2.3-7.5) point adjusted mean relative decline at 12 months. In the Nocturnal Trial, subjects randomized to frequent nocturnal as compared with conventional home hemodialysis experienced 2.9 (95% CI -3.4-9.3) and 4.5 (95% CI -3.2-12.2) point mean relative declines at Months 4 and 12, respectively. CONCLUSIONS: Although a possible benefit of frequent in-center hemodialysis was observed at 4 months, neither frequent in-center hemodialysis nor home nocturnal hemodialysis demonstrated significant improvements in self-reported sleep quality compared with conventional hemodialysis at 12 months. PMID- 27190362 TI - Deceased donor kidney transplantation across donor-specific antibody barriers: predictors of antibody-mediated rejection. AB - BACKGROUND: Apheresis-based desensitization allows for successful transplantation across major immunological barriers. For donor-specific antibody (DSA)- and/or crossmatch-positive transplantation, however, it has been shown that even intense immunomodulation may not completely prevent antibody-mediated rejection (ABMR). METHODS: In this study, we evaluated transplant outcomes in 101 DSA+ deceased donor kidney transplant recipients (transplantation between 2009 and 2013; median follow-up: 24 months) who were subjected to immunoadsorption (IA)-based desensitization. Treatment included a single pre-transplant IA session, followed by anti-lymphocyte antibody and serial post-transplant IA. In 27 cases, a positive complement-dependent cytotoxicity crossmatch (CDCXM) was rendered negative immediately before transplantation. Seventy-four of the DSA+ recipients had a negative CDCXM already before IA. RESULTS: Three-year death-censored graft survival in DSA+ patients was significantly worse than in 513 DSA- recipients transplanted during the same period (79 versus 88%, P = 0.008). Thirty-three DSA+ recipients (33%) had ABMR. While a positive baseline CDCXM showed only a trend towards higher ABMR rates (41 versus 30% in CDCXM- recipients, P = 0.2), DSA mean fluorescence intensity (MFI) in single bead assays significantly associated with rejection, showing 20 versus 71% ABMR rates at <5000 versus >15 000 peak DSA MFI. The predictive value of MFI was moderate, with the highest accuracy at a median of 13 300 MFI (after cross-validation: 0.72). Other baseline variables, including CDC assay results, human leukocyte antigen mismatch, prior transplantation or type of induction treatment, did not add independent predictive information. CONCLUSIONS: IA-based desensitization failed to prevent ABMR in a considerable number of DSA+ recipients. Assessing DSA MFI may help stratify risk of rejection, supporting its use as a guide to organ allocation and individualized treatment. PMID- 27190363 TI - Causality at the dawn of the 'omics' era in medicine and in nephrology. AB - Causality is a core concept in medicine. The quantitative determinacy characterizing today's biomedical science is unprecedented. The assessment of causal relations in human diseases is evolving, and it is therefore fundamental to keep up with the steady pace of theoretical and technological advancements. The exact specification of all causes of pathologies at the individual level, precision medicine, is expected to allow the complete eradication of disease. In this article, we discuss the various conceptualizations of causation that are at play in the context of randomized clinical trials and observational studies. Genomics, proteomics, metabolomics and epigenetics can now produce the precise knowledge we need for 21st century medicine. New conceptions of causality are needed to form the basis of the new precision medicine. PMID- 27190364 TI - Kidney transplantation due to medical urgency: time for reconsideration? PMID- 27190361 TI - Impact of individual intravenous iron preparations on the differentiation of monocytes towards macrophages and dendritic cells. AB - BACKGROUND: Treatment of iron deficiency with intravenous (i.v.) iron is a first line strategy to improve anaemia of chronic kidney disease. Previous in vitro experiments demonstrated that different i.v. iron preparations inhibit differentiation of haematopoietic stem cells to monocytes, but their effect on monocyte differentiation to macrophages and mature dendritic cells (mDCs) has not been assessed. We investigated substance-specific effects of iron sucrose (IS), sodium ferric gluconate (SFG), ferric carboxymaltose (FCM) and iron isomaltoside 1000 (IIM) on monocytic differentiation to M1/M2 macrophages and mDCs. METHODS: Via flow cytometry and microRNA (miRNA) expression analysis, we morphologically and functionally characterized monocyte differentiation to M1/M2 macrophages and mDCs after monocyte stimulation with IS, SFG, FCM and IIM (0.133, 0.266 and 0.533 mg/mL, respectively). To assess potential clinical implications, we compared monocytic phagocytosis capacity in dialysis patients who received either 500 mg IS or IIM. RESULTS: Phenotypically, IS and SFG dysregulated the expression of macrophage (e.g. CD40, CD163) and mDC (e.g. CD1c, CD141) surface markers. Functionally, IS and SFG impaired macrophage phagocytosis capacity. Phenotypic and functional alterations were less pronounced with FCM, and virtually absent with IIM. In miRNA expression analysis of mDCs, IS dysregulated miRNAs such as miR-146b-5p and miR-155-5p, which are linked to Toll-like receptor and mitogen activated protein kinase signalling pathways. In vivo, IS reduced monocytic phagocytosis capacity within 1 h after infusion, while IIM did not. CONCLUSIONS: This study demonstrates that less stable i.v. iron preparations specifically affect monocyte differentiation towards macrophages and mDCs. PMID- 27190366 TI - Indirect estimation of nephron number: a new tool to predict outcomes in renal transplantation? PMID- 27190365 TI - Curcumin ameliorates nephrosclerosis via suppression of histone acetylation independent of hypertension. AB - BACKGROUND: Although histone acetylation, an epigenetic modification, has been reported to be related to the progression of various diseases, its involvement in nephrosclerosis is unclear. METHODS: Dahl salt-sensitive rats were used as a model of nephrosclerosis in this study. The rats were divided into three groups: (i) normal-salt diet group, (ii) high-salt diet group (HS), and (iii) HS administered daily with curcumin, a histone acetyltransferase inhibitor (HS+C). At 6 weeks after the treatment, the kidneys were dissected. Morphologic changes were assessed by Masson's trichrome staining. The number of macrophages, fibroblasts and the cells expressing acetylated histone H3 at Lys 9 (H3K9) were assessed by immunohistochemistry. RESULTS: Although both HS and HS+C rats revealed a marked increase in systolic blood pressure, serum creatinine was increased only in HS rats at 6 weeks. In the HS rats, nephrosclerosis was induced, accompanying a significant accumulation of macrophages and fibroblasts. The inflammation and fibrosis was markedly suppressed in the HS+C group. The level of histone acetylation at Lys 9 was enhanced in the HS rats, whereas curcumin administration suppressed the histone acetylation. Moreover, in the HS rats, interleukin-6 gene expression was associated with acetylated H3K9, as revealed by chromatin immunoprecipitation assay. CONCLUSIONS: Our results suggested that curcumin ameliorates nephrosclerosis via suppression of histone acetylation, independently of hypertension. PMID- 27190369 TI - Dynamics and epitope specificity of anti-human leukocyte antibodies following renal allograft nephrectomy. AB - BACKGROUND: A considerable proportion of patients awaiting kidney transplantation is immunized by previous transplantation(s). We investigated how allograft nephrectomy (Nx) and withdrawal of maintenance immunosuppression (WD-MIS) in patients with a failed renal allograft contribute to allosensitization. METHODS: HLA antibodies (HLAabs) were analyzed before and after Nx and/or WD-MIS using a single antigen bead assay. Patients were grouped as follows: (A) Nx and concomitant WD-MIS (n = 28), (B) Nx (n = 14) and (C) WD-MIS (n = 12). In a subgroup of patients, the epitope specificity of HLAabs was determined by adsorption and elution of sera with recombinant single HLA allele-expressing cell lines. RESULTS: Following Nx and/or WD-MIS, HLAabs were detectable in 100, 100 and 92% of patients in Groups A, B and C, respectively. In patients of all groups, de novo donor-specific HLAabs (DSAs) were found. After Nx, an increase in the breadth [percent panel reactive antibody (%PRA)] and mean fluorescence intensity of class I HLAabs was predominant. In contrast, an increase of class II HLAabs prevailed following WD-MIS. Experimental analysis of the epitope specificities revealed that 64% of the class I HLAabs classically denoted as non DSA were donor epitope-specific HLAabs (DESA). CONCLUSIONS: Both Nx and WD-MIS contribute to alloimmunization with differing patterns concerning class I and II HLAabs. Nx preferentially increased class I HLAabs and most of the observed class I HLAabs were DESA. Considering that class I, but not class II, HLA molecules are constitutively expressed, our results support the hypothesis that the increase of HLAabs following Nx might have been caused by removal of the adsorbing donor tissue (sponge hypothesis). PMID- 27190368 TI - Chronicity following ischaemia-reperfusion injury depends on tubular-macrophage crosstalk involving two tubular cell-derived CSF-1R activators: CSF-1 and IL-34. AB - Two structurally unrelated ligands activate the macrophage colony stimulating factor receptor (CSF-1R, c-fms, CD115): M-CSF/CSF-1 and interleukin-34 (IL-34). Both ligands promote macrophage proliferation, survival and differentiation. IL 34 also activates the protein-tyrosine phosphatase zeta receptor (PTP-zeta, PTPRZ1). Both receptors and cytokines are increased during acute kidney injury. While tubular cell-derived CSF-1 is required for kidney repair, Baek et al (J Clin Invest 2015; 125: 3198-3214) have now identified tubular epithelial cell derived IL-34 as a promoter of kidney neutrophil and macrophage infiltration and tubular cell destruction during experimental kidney ischaemia-reperfusion, leading to chronic injury. IL-34 promoted proliferation of both intrarenal macrophages and bone marrow cells, increasing circulating neutrophils and monocytes and their kidney recruitment. Thus, injured tubular cells release two CSF-1R activators, one (CSF-1) that promotes tubular cell survival and kidney repair and another (IL-34) that promotes chronic kidney damage. These results hold promise for the development of IL-34-targeting strategies to prevent ischaemia-reperfusion kidney injury in contexts such as kidney transplantation. However, careful consideration should be given to the recent characterization by Bezie et al. (J Clin Invest 2015; 125: 3952-3964) of IL-34 as a T regulatory cell (Treg) cytokine that modulates macrophage responses so that IL-34-primed macrophages potentiate the immune suppressive capacity of Tregs and promote graft tolerance. PMID- 27190367 TI - Association of serum vitamin B12 and folate with mortality in incident hemodialysis patients. AB - Background: Vitamin B12 (B12) and folate are essential vitamins that play important roles in physiological processes. In the general population, many studies have evaluated the association of these vitamins with clinical outcomes, yet this association in hemodialysis (HD) patients remains unclear. Methods: We examined the association of serum folate and B12 with mortality in a 5-year cohort of 9517 (folate) and 12 968 (B12) HD patients using Cox models with hierarchical adjustment for sociodemographics, comorbidities, and laboratory variables associated with the malnutrition and inflammation complex syndrome. The associations of baseline B12 and folate (separately) with all-cause mortality were evaluated across five categories of B12 [<400 (reference), 400-<550, 550 <650, 650-<750 and >=750 pg/mL] and folate [<6.2, 6.2-<8.4, 8.4-<11 (reference), 11-<14.3 and >=14.3 ng/mL]. Results: The study cohort with B12 measurements had a mean +/- standard deviation age of 63 +/- 15 years, among whom 43% were female, 33% were African-American, and 57% were diabetic. Higher B12 concentrations >=550 pg/mL were associated with a higher risk of mortality after adjusting for sociodemographic and laboratory variables. However, only lower serum folate concentrations <6.2 ng/mL were associated with a higher risk of all-cause mortality when adjusted for sociodemographic variables [adjusted hazard ratio (95% confidence-interval): 1.18 (1.03-1.35)]. Conclusions: Higher B12 concentrations are associated with higher all-cause mortality in HD patients independent of sociodemographics and laboratory variables, whereas lower folate concentrations were associated with higher all-cause mortality after accounting for sociodemographic variables. Further studies are warranted to determine the optimal B12 and folate level targets in this population. PMID- 27190370 TI - Acetazolamide enhances the release of urinary exosomal aquaporin-1. AB - BACKGROUND: Renal aquaporin-1 (AQP1), a water channel protein, is known to be secreted into urine, conveyed by nano-sized extracellular vesicles called exosomes. A previous study has demonstrated that acetazolamide (AZ), a diuretic that inhibits carbonic anhydrases, alters the expression level of AQP1 in cultured cells. Here we investigated whether AZ alters the release of urinary exosomal AQP1 in vivo. METHODS: The effect of AZ on urinary exosomal AQP1 secretion was examined in rats and compared with furosemide (another diuretic), NaHCO3 (an alkalizing agent) and NH4Cl (an acidifying agent). Urine, blood and kidney samples were obtained 2 h after each treatment. Urinary exosomes were isolated by a differential centrifugation technique and urinary exosomal proteins were analyzed by immunoblotting. RESULTS: The release of exosomal AQP1 into urine was markedly increased after treatment with AZ, accompanied by alkaluria and metabolic acidosis. Immunohistochemistry clearly demonstrated that AZ increased the apical membrane expression of AQP1 in the proximal tubules. AZ did not affect the release of exosomal marker proteins (tumor susceptibility gene 101 protein and apoptosis-linked gene 2 interacting protein X). Treatment with furosemide did not change, whereas NaHCO3 and NH4Cl decreased the exosomal release of AQP1. CONCLUSION: The present findings indicate that AZ increases the release of exosomal AQP1 into urine in association with enhanced apical membrane expression of AQP1. PMID- 27190371 TI - Elevated urinary podocyte-derived extracellular microvesicles in renovascular hypertensive patients. AB - Background: An increased number of podocyte-derived extracellular vesicles (pEVs) may reflect podocyte injury in renal disease. Elevated glomerular pressure and other insults may injure podocytes, yet it remains unclear whether the numbers of pEVs are altered in hypertensive patients. We tested the hypothesis that urinary pEV levels would be elevated in patients with renovascular hypertension (RVH) compared with essential hypertension (EH) or healthy volunteers (HVs). Methods: We prospectively enrolled patients with EH ( n = 30) or RVH ( n = 31) to study renal blood flow (RBF) and cortical perfusion using multidetector computed tomography under controlled condition (regulated sodium intake and renin angiotensin blockade). After isolation from urine samples, pEVs (nephrin and podocalyxin positive) were characterized by flow cytometry. Fourteen RVH patients were studied again 3 months after stenting or continued medical therapy. HVs ( n = 15) served as controls. Results: The fraction of pEV among urinary EVs was elevated in RVH compared with HVs and EH (11.4 +/- 6.4, 6.8 +/- 3.4 and 6.3 +/- 3.7%, respectively; P < 0.001) and remained unchanged after 3 additional months of therapy and after controlling for clinical parameters. However, eGFR- and age adjusted pEV levels did not correlate with any clinical or renal parameters. Conclusions: In hypertensive patients under controlled conditions, urinary pEV levels are elevated in patients with RVH and low eGFR compared with patients with EH and relatively preserved renal function. These pEVs may reflect podocyte injury secondary to kidney damage, and their levels might represent a novel therapeutic target. PMID- 27190372 TI - Mild prolonged chronic hyponatremia and risk of hip fracture in the elderly. AB - BACKGROUND: Hip fractures are among the most serious bone fractures in the elderly, producing significant morbidity and mortality. Several observational studies have found that mild hyponatremia can adversely affect bone, with fractures occurring as a potential complication. We examined if there is an independent association between prolonged chronic hyponatremia (>90 days duration) and risk of hip fracture in the elderly. METHODS: We performed a retrospective cohort study in adults >60 years of age from a prepaid health maintenance organization who had two or more measurements of plasma sodium between 2005 and 2012. The incidence of hip fractures was assessed in a very restrictive population: subjects with prolonged chronic hyponatremia, defined as plasma sodium values <135 mmol/L, lasting >90 days. Multivariable Cox regression was performed to determine the hazard ratio (HR) for hip fracture risk associated with prolonged chronic hyponatremia after adjustment for the propensity to have hyponatremia, fracture risk factors and relevant baseline characteristics. RESULTS: Among 31 527 eligible patients, only 228 (0.9%) had prolonged chronic hyponatremia. Mean plasma sodium was 132 +/- 5 mmol/L in hyponatremic patients and 139 +/- 3 mmol/L in normonatremic patients (P < 0.001). The absolute risk for hip fracture was 7/282 in patients with prolonged chronic hyponatremia and 411/313 299 in normonatremic patients. Hyponatremic patients had a substantially elevated rate of hip fracture [adjusted HR 4.52 (95% CI 2.14-9.6)], which was even higher in those with moderate hyponatremia (<130 mmol/L) [adjusted HR 7.61 (95% CI 2.8-20.5)]. CONCLUSION: Mild prolonged chronic hyponatremia is independently associated with hip fracture risk in the elderly population, although the absolute risk is low. However, proof that correcting hyponatremia will result in a reduction of hip fractures is lacking. PMID- 27190373 TI - Factors influencing withdrawal from dialysis: a national registry study. AB - BACKGROUND: Dialysis withdrawal is the third most common cause of death in patients receiving dialysis for established renal failure (ERF) in Scotland. We describe incidence, risk factors and themes influencing decision-making in a national renal registry. METHODS: Details of deaths in those receiving renal replacement therapy (RRT) for ERF in Scotland are reported to the Scottish Renal Registry via a unique mortality report. We extracted patient demographics and comorbidity, cause and location of death, duration of RRT and pertinent free text comments from 1 January 2008 to 31 December 2014. Withdrawal incidence was calculated and logistic regression used to identify significantly influential variables. Themes emerging from clinician comments were tabulated for descriptive purposes. RESULTS: There were 2596 deaths; median age at death was 68 [interquartile range (IQR) 58, 76] years, 41.5% were female. Median duration on RRT was 1110 (IQR 417, 2151) days. Dialysis withdrawal was the primary cause of death in 497 (19.1%) patients and withdrawal contributed to death in a further 442 cases (17.0%). The incidence was 41 episodes per 1000 patient-years. Regression analysis revealed increasing age, female sex and prior cerebrovascular disease were associated with dialysis withdrawal as a primary cause of death. Conversely, interstitial renal disease, angiographically proven ischaemic heart disease, valvular heart disease and malignancy were negatively associated. Analysis of free text comments revealed common themes, portraying an image of physical and psychological decline accelerated by acute illnesses. CONCLUSIONS: Death following dialysis withdrawal is common. Factors important to physical independence-prior cerebrovascular disease and increasing age-are associated with withdrawal. When combined with clinician comments this study provides an insight into the clinical decline affecting patients and the complexity of this decision. Early recognition of those likely to withdraw may improve end of life care. PMID- 27190375 TI - The effects of short sleep duration on proteinuria and chronic kidney disease: a systematic review and meta-analysis. AB - Background: The risks of proteinuria and chronic kidney disease (CKD) in adults who regularly have short sleep duration (short sleepers) are controversial. The aim of this meta-analysis was to assess the effects of short sleep duration on proteinuria and CKD. Methods: A literature search was conducted using MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews from the inception of the databases through November 2015. Studies that reported relative risks, odd ratios or hazard ratios comparing the risks of proteinuria and CKD in short sleepers were included. Pooled risk ratios (RR) and 95% confidence intervals (CI) were computed utilizing a random-effect, generic inverse variance method. Results: Six observational studies with 252 075 individuals and three observational studies with 37 197 individuals were included in the analyses to assess the risks of CKD and proteinuria in short sleepers, respectively. The pooled RR of CKD in short sleepers was 1.51 (95% CI, 0.99-2.55). When meta-analysis was restricted only to studies with adjusted analysis for confounders assessing the risk of CKD in short sleepers, the pooled RR of CKD was 1.54 (95% CI, 0.80-2.95). The pooled RR of proteinuria in short sleepers was 1.47 (95% CI, 1.26-1.72). Conclusions: Despite the lack of significant association between short sleep duration and CKD, our meta-analysis suggests a potential association between short sleep duration and proteinuria, a surrogate marker for kidney disease progression. Future study is required to investigate if reversal of short sleep helps reduce proteinuria. PMID- 27190374 TI - Impact of using two dialyzers in parallel on phosphate clearance in hemodialysis patients: a randomized trial. AB - Background: Dietary restriction and phosphate binders are the main interventions used to manage hyperphosphatemia in people on hemodialysis, but have limited efficacy. Modifying conventional dialysis regimens to enhance phosphate clearance as an alternative approach remains relatively unstudied. Methods: This was a 10 week, 2-arm, randomized crossover study. Participants were prevalent dialysis patients ( n = 32) with consecutive serum phosphate levels >1.6 mmol/L and on stable doses of a phosphate binder. Following a 2-week run-in period, participants were randomized to initiate dialysis using two high flux dialyzers in parallel (blood flow >=350 mL/min, dialysate flow 800 mL/min) or standard dialysis using one high flux dialyzer (blood flow >=350 mL/min, dialysate flow of 800 mL/min). Each regimen was 3 weeks in duration. After a 2-week washout period, participants received the alternate regimen. The primary outcome was the mean difference in phosphate clearance by dialyzer strategy. Secondary outcomes were phosphate removal and pre-dialysis serum phosphate. Results: Phosphate clearance for the double dialyzer strategy did not differ significantly from the single dialyzer strategy [mean difference 7.5 mL/min (95% confidence interval, 95% CI, 6.1, 21.0), P = 0.28]. There was no difference in total phosphate removal and pre dialysis phosphate between the double and single dialyzer strategies [total phosphate removal mean difference -0.2 mmol (95% CI -4.1, 3.7), P = 0.93; pre dialysis mean difference 0.01 mmol/L (95% CI -0.18, 0.21), P = 0.88]. There was no difference in the proportion of participants who experienced at least one episode of intradialytic hypotension (32 versus 47%, P = 0.13). A limitation of the study was frequent protocol deviations in the dialysis prescription. Conclusions: In this study, the use of two dialyzers in parallel did not increase phosphate clearance, phosphate removal or pre-dialysis serum phosphorus when compared with a standard dialysis treatment strategy. Future studies should continue to evaluate novel methods of phosphate removal using conventional hemodialysis. PMID- 27190376 TI - A novel COL4A1 frameshift mutation in familial kidney disease: the importance of the C-terminal NC1 domain of type IV collagen. AB - BACKGROUND: Hereditary microscopic haematuria often segregates with mutations of COL4A3, COL4A4 or COL4A5 but in half of families a gene is not identified. We investigated a Cypriot family with autosomal dominant microscopic haematuria with renal failure and kidney cysts. METHODS: We used genome-wide linkage analysis, whole exome sequencing and cosegregation analyses. RESULTS: We identified a novel frameshift mutation, c.4611_4612insG:p.T1537fs, in exon 49 of COL4A1. This mutation predicts truncation of the protein with disruption of the C-terminal part of the NC1 domain. We confirmed its presence in 20 family members, 17 with confirmed haematuria, 5 of whom also had stage 4 or 5 chronic kidney disease. Eleven family members exhibited kidney cysts (55% of those with the mutation), but muscle cramps or cerebral aneurysms were not observed and serum creatine kinase was normal in all individuals tested. CONCLUSIONS: Missense mutations of COL4A1 that encode the CB3 [IV] segment of the triple helical domain (exons 24 and 25) are associated with HANAC syndrome (hereditary angiopathy, nephropathy, aneurysms and cramps). Missense mutations of COL4A1 that disrupt the NC1 domain are associated with antenatal cerebral haemorrhage and porencephaly, but not kidney disease. Our findings extend the spectrum of COL4A1 mutations linked with renal disease and demonstrate that the highly conserved C-terminal part of the NC1 domain of the alpha1 chain of type IV collagen is important in the integrity of glomerular basement membrane in humans. PMID- 27190378 TI - Should we aim for oral health to improve outcomes in chronic kidney disease? PMID- 27190377 TI - Aortic stiffness and change in glomerular filtration rate and albuminuria in older people. AB - Background: Aortic stiffness increases with age and increases pulsatile stress in the microcirculation. Abnormalities in kidney microvascular structure and function may contribute to development or progression of chronic kidney disease in older people. Methods: We performed a longitudinal analysis of 629 community dwelling elderly Icelandic adults from the Age, Gene/Environment Susceptibility Reykjavik Study with two visits over a mean follow-up of 5.3 years. We evaluated the associations of carotid-femoral pulse wave velocity (CFPWV), carotid pulse pressure (CPP) and augmentation index (AI), with the change in estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) assessed as annual change and dichotomized as large changes. Models were adjusted for age, sex, height, heart rate, traditional cardiovascular disease risk factors and baseline kidney measures. Results: When eGFR was analyzed as a continuous variable, higher baseline CFPWV and CPP, but not AI, were significantly associated with a larger annual decline in eGFR in models adjusted for age, sex, height, heart rate and baseline eGFR, but not after additional adjustment for the mean arterial pressure. When eGFR was analyzed as a categorical variable, higher CFPWV was significantly associated with a decrease in eGFR of >=3 mL/min/1.73 m 2 /year [odds ratio (OR) 1.53, 95% confidence interval (CI) 1.11-2.13] and higher AI was associated with 30% eGFR decline during follow-up (OR 1.44 and 95% CI 1.03 2.00) in fully adjusted models. None of the tonometry measures was associated with change in UACR. Conclusions: Abnormalities in vascular health may play a role in large declines in eGFR beyond the traditional cardiovascular disease risks in this older Icelandic cohort. PMID- 27190379 TI - The natural history of immunoglobulin M nephropathy in adults. AB - Background: Immunoglobulin M (IgM) nephropathy is an idiopathic glomerulonephritis characterized by diffuse mesangial deposition of IgM. IgM nephropathy has been a controversial diagnosis since it was first reported, and there are few data identifying specific pathological features that predict the risk of progression of renal disease. Methods: We identified 57 cases of IgM nephropathy among 3220 adults undergoing renal biopsy at our institution. Biopsies had to satisfy the following three criteria to meet the definition of IgM nephropathy in this study: (i) dominant mesangial staining for IgM, (ii) mesangial deposits on electron microscopy (EM) and (iii) exclusion of systemic disease. Results: The median age was 42 years and 24 patients were male. Thirty nine per cent of patients presented with the nephrotic syndrome, 49% presented with non-nephrotic proteinuria and 39% had eGFR <60 mL/min. The median post biopsy follow-up was 40 months and serum creatinine had doubled in 31% by 5 years. Of histological parameters, glomerular sclerosis and tubular atrophy, but not mesangial proliferation, were risk factors for renal insufficiency. Thirty nine per cent of nephrotic patients achieved complete remission, and outcome was significantly worse in those who did not respond to treatment. Focal segmental glomerulosclerosis was diagnosed in 80% of those undergoing repeat renal biopsy, despite ongoing mesangial IgM deposition. Conclusions: We propose criteria for a consensus definition of IgM nephropathy. PMID- 27190380 TI - Lung ultrasound: a novel technique for detecting fluid overload in children on dialysis. AB - Background: Optimizing the target weight of infants and children on dialysis remains an important clinical challenge. The use of ultrasound to detect fluid overload in adult patients on dialysis is receiving growing attention. We hypothesized that fluid overload can be quantified in infants and children receiving dialysis using lung ultrasound. Methods: In this prospective observational study, infants and children receiving dialysis for end-stage renal disease (ESRD) or acute kidney injury (AKI) in a regional paediatric nephrology centre were eligible. Lung ultrasound examinations were performed during in centre dialysis, on home visits or in an outpatient clinic. Fluid overload was assessed by quantifying B-lines on ultrasound and compared with proportional (%) increase in patient weight from the target weight. Results: A total of 142 ultrasound assessments were performed in 23 children. In children with AKI, median B-line score reduced from 5 (range 0-22) at presentation to 1.5 (0-4) at recovery (P = 0.04) with concurrent improvement in fluid overload judged by weight from 7.2 (-1.9 to 15.2)% to 0%. A linear correlation between lung ultrasound B-line score and fluid overload judged by weight was observed in children with AKI (r = 0.83) and ESRD (r = 0.61). Inter-observer variability was acceptable. Conclusions: Lung ultrasound is a practical and sensitive method of quantifying subclinical fluid overload in infants and children on dialysis. Interventional studies to determine the benefits of using lung ultrasound to optimize the target weight for children with ESRD are merited. PMID- 27190381 TI - Prevalence of reduced kidney function and albuminuria in older adults: the Berlin Initiative Study. AB - Background: Although CKD is said to increase among older adults, epidemiologic data on kidney function in people >=70 years of age are scarce. The Berlin Initiative Study (BIS) aims to fill this gap by evaluating the CKD burden in older adults. Methods: The BIS is a prospective population-based cohort study whose participants are members of Germany's biggest insurance company. This cross sectional analysis (i) gives a detailed baseline characterization of the participants, (ii) analyses the representativeness of the cohort's disease profile, (iii) assesses GFR and albuminuria levels across age categories, (iv) associates cardiovascular risk factors with GFR as well as albuminuria and (v) compares means of GFR values according to different estimating equations with measured GFR. Results: A total of 2069 participants (52.6% female, mean age 80.4 years) were enrolled: 26.1% were diabetic, 78.8% were on antihypertensive medication, 8.7% had experienced a stroke, 14% a myocardial infarction, 22.6% had cancer, 17.8% were anaemic and 26.5% were obese. The distribution of comorbidities in the BIS cohort was very similar to that in the insurance 'source population'. Creatinine and cystatin C as well as the albumin:creatinine ratio (ACR) increased with increasing age. After multivariate adjustments, reduced GFR and elevated ACR were associated with most cardiovascular risk factors. The prevalence of a GFR <60 mL/min/1.73 m 2 ranged from 38 to 62% depending on the estimation equation used. Conclusions: The BIS is a very well-characterized, representative cohort of older adults. Participants with an ACR >=30 had significantly higher odds for most cardiovascular risk factors compared with an ACR <30 mg/g. Kidney function declined and ACR rose with increasing age. PMID- 27190382 TI - Systemic complement activation and complement gene analysis in enterohaemorrhagic Escherichia coli-associated paediatric haemolytic uraemic syndrome. AB - BACKGROUND: In contrast to atypical haemolytic uraemic syndrome (aHUS), only single case reports and limited data have been published on systemic activation of the complement system and mutations in complement genes in paediatric enterohaemorrhagic Escherichia coli-induced HUS (EHEC-HUS). METHODS: Complement activation (CH50, APH50, C3d, sC5b-9) was analysed at four timepoints (Week 1, Week 2, Month 3 and Month 6 after primary diagnosis of HUS) in 25 children with EHEC-HUS. Seven patients received the complement C5 inhibitor eculizumab. Targeted next generation sequencing for a total of 89 genes involved in complement regulation and coagulation and haemostasis was performed in all patients. RESULTS: Activity of classical (CH50) and alternative (APH50) complement pathways was normal or even elevated throughout the observation time, except for patients under eculizumab treatment. In contrast, the mean concentration of the soluble terminal complement complex (sC5b-9) was significantly elevated at the first timepoint (mean 498 ng/mL), dropping to normal values after 2 weeks. Initially elevated (42 mU/L) median C3d concentration reached normal levels from Week 2. Levels of sC5b-9 >320 ng/mL at the time of HUS diagnosis were associated with arterial hypertension, oedema and lower platelet counts, but not with the duration of dialysis. Genetic analysis revealed various changes that may have had a modifying impact on the clinical course. CONCLUSIONS: Complement activation at the acute phase of EHEC-HUS, indicated by increased levels of sC5b-9, predicts a poor outcome. Complement alterations appear to be more frequent in patients with EHEC-HUS than previously thought and are suspected to have a role in the severity of the disease. PMID- 27190384 TI - Immunosuppression with mammalian target of rapamycin inhibitor and incidence of post-transplant cancer in kidney transplant recipients. AB - BACKGROUND: Evidence is limited regarding the effect of de novo therapy with mammalian target of rapamycin (mTOR) inhibitors on cancer risk after kidney transplantation. METHODS: Collaborative Transplant Study data from 78 146 adult recipients of first deceased-donor kidney transplants (1999-2013) were analysed (4279 mTOR inhibitor, 73 867 no mTOR inhibitor) using standard methods. Propensity score matching was performed for analysis of basal cell and squamous cell skin cancer. RESULTS: Standardized incidence ratios (SIR) versus a matched non-transplant population showed reduced tumour incidence in recipients with de novo mTOR inhibitor therapy compared with no mTOR inhibitor for non-melanoma skin cancer (NMSC) (SIR 5.1 versus 6.1; P =0.019) but not non-NMSC cancers (SIR 1.6 versus 1.7; P =0.35). Within propensity score-matched groups (n = 4265), multivariable Cox regression analysis showed a trend to reduced NMSC with mTOR inhibition [hazard ratio (HR) 0.77; P =0.063] but not for all non-NMSC tumours (HR 0.94; P= 0.59). A significant effect for mTOR inhibition was observed for basal cell carcinoma of the skin (HR 0.56; P= 0.004) but not squamous cell carcinoma (HR 0.87; P= 0.54). CONCLUSIONS: De novo mTOR inhibition was associated with a substantially and significantly reduced risk of basal cell carcinoma of the skin after kidney transplantation. A significant reduction of the incidence of other cancers was not found. PMID- 27190385 TI - Factors influencing pathological ankle-brachial index values along the chronic kidney disease spectrum: the NEFRONA study. AB - Background: The ankle-brachial index (ABI) is widely used to diagnose subclinical peripheral artery disease (PAD) in the general population, but data assessing its prevalence and related factors in different chronic kidney disease (CKD) stages are scarce. The aim of this study is to evaluate the prevalence and associated factors of pathological ABI values in CKD patients. Methods: NEFRONA is a multicentre prospective project that included 2445 CKD patients from 81 centres and 559 non-CKD subjects from 9 primary care centres across Spain. A trained team collected clinical and laboratory data, performed vascular ultrasounds and measured the ABI. Results: PAD prevalence was higher in CKD than in controls (28.0 versus 12.3%, P < 0.001). Prevalence increased in more advanced CKD stages, due to more patients with an ABI >=1.4, rather than <=0.9. Diabetes was the only factor predicting both pathological values in all CKD stages. Age, female sex, carotid plaques, higher carotid intima-media thickness, higher high-sensitivity C reactive protein (hsCRP) and triglycerides, and lower 25-hydroxi-vitamin D were independently associated with an ABI <=0.9. Higher phosphate and hsCRP, lower low density lipoprotein (LDL)-cholesterol and dialysis were associated with an ABI >=1.4. A stratified analysis showed different associated factors in each CKD stage, with phosphate being especially important in earlier CKD, and LDL cholesterol being an independent predictor only in Sage 5D CKD. Conclusions: Asymptomatic PAD is very prevalent in all CKD stages, but factors related to a low or high pathological ABI differ, revealing different pathogenic pathways. Diabetes, dyslipidaemia, inflammation and mineral-bone disorders play a role in the appearance of PAD in CKD. PMID- 27190386 TI - Efficacy and safety of antibody induction therapy in the current era of kidney transplantation. AB - BACKGROUND: Antibody induction with polyclonal rabbit-antithymocyte globulin (rATG) or an interleukin-2 receptor antagonist (IL-2RA) is widely used in kidney transplantation. METHODS: Collaborative Transplant Study data from 38 311 first deceased-donor kidney transplants (2004-13) were analysed. Transplants were classified as 'normal risk' or 'increased risk' according to current guidelines. Cox regression analysis was applied to subpopulations of propensity score-matched recipients. RESULTS: rATG or IL-2RA induction was given to 64% of increased-risk and 53% of normal-risk patients, respectively. rATG and IL-2RA induction were each associated with reduced risk for graft loss versus no induction in increased risk patients [hazard ratio (HR) 0.85, P = 0.046 and HR 0.89, P = 0.011, respectively]. The HR values for incidence of treated rejection in increased-risk patients for rATG and IL-2RA versus no induction were 0.75 (P = 0.037) and 0.77 (P < 0.001), respectively. In the normal risk subpopulation, neither induction therapy significantly affected the risk of graft loss or treated rejection. Hospitalization for infection was increased by rATG (P < 0.001) and IL-2RA (P < 0.001) induction. In contrast to patients transplanted during 1994-2003, among patients transplanted during 2004-13, rATG did not significantly affect the risk of non-Hodgkin's lymphoma versus no induction (P = 0.68). CONCLUSION: Induction therapy following kidney transplantation should be targeted to increased-risk transplants. In this analysis, a beneficial effect of antibody induction in normal-risk transplants could not be demonstrated. PMID- 27190383 TI - Matrix metalloproteinase 9 is associated with peritoneal membrane solute transport and induces angiogenesis through beta-catenin signaling. AB - Background: For patients using peritoneal dialysis (PD), the peritoneal membrane can develop fibrosis and angiogenesis, leading to ultrafiltration failure, chronic hypervolemia and increased risk of technique failure and mortality. Matrix metalloproteinases (MMPs), and specifically the gelatinases (MMP2 and MMP9), may be involved in peritoneal membrane injury. Methods: From stable PD patients, mesothelial cells were assayed for MMP gene expression. MMP9 was overexpressed in mouse peritoneum by adenovirus, and MMP9 -/- mice were subjected to transforming growth factor beta (TGF-beta)-induced peritoneal fibrosis. Results: MMP9 mRNA expression correlated with peritoneal membrane solute transport properties. Overexpression of MMP9 in the mouse peritoneum induced submesothelial thickening and angiogenesis. MMP9 induced mesothelial cell transition to a myofibroblast phenotype measured by increased alpha smooth muscle actin and decreased E-cadherin expression. Angiogenesis was markedly reduced in MMP9 -/- mice treated with an adenovirus expressing active TGF-beta compared with wild-type mice. TGF-beta-mediated E-cadherin cleavage was MMP9 dependent, and E cadherin cleavage led to beta-catenin-mediated signaling. A beta-catenin inhibitor blocked the angiogenic response induced by AdMMP9. Conclusions: Our data suggest that MMP9 is involved in peritoneal membrane injury possibly through cleavage of E-cadherin and induction of beta-catenin signaling. MMP9 is a potential biomarker for peritoneal membrane injury and is a therapeutic target to protect the peritoneal membrane in PD patients. PMID- 27190387 TI - Opponent's comments. PMID- 27190388 TI - Opponent's comments. PMID- 27190391 TI - Opponent's comments. PMID- 27190390 TI - Pro: Should we correct vitamin D deficiency/insufficiency in chronic kidney disease patients with inactive forms of vitamin D or just treat them with active vitamin D forms? AB - Evidence for the usefulness of using vitamin D to treat 'renal bone disease' is now nearly six decades old. In regular clinical practice, however, it is more like three decades, at most, that we have routinely been using vitamin D to try to prevent, or reverse, the impact of hyperparathyroidism on the skeleton of patients with chronic kidney disease (CKD). The practice has been in the main to use high doses of synthetic vitamin D compounds, not naturally occurring ones. However, the pharmacological impacts of the different vitamin D species and of their different modes, and styles of administration cannot be assumed to be uniform across the spectrum. It is disappointingly true to say that even in 2016 there is a remarkable paucity of evidence concerning the clinical benefits of vitamin D supplementation to treat vitamin D insufficiency in patients with stage 3b-5 CKD. This is even more so if we consider the non-dialysis population. While there are a number of studies that report the impact of vitamin D supplementation on serum vitamin D concentrations (unsurprisingly, usually reporting an increase), and some variable evidence of parathyroid hormone concentration suppression, there has been much less focus on hard or semi-rigid clinical end point analysis (e.g. fractures, hospitalizations and overall mortality). Now, in 2016, with the practice pattern changes of first widespread clinical use of vitamin D and second widespread supplementation of cholecalciferol or ergocalciferol by patients (alone, or as multivitamins), it is now, in my view, next to impossible to run a placebo-controlled trial over a decent period of time, especially one which involved clinically meaningful (fractures, hospitalisation, parathyroidectomy, death) end-points. In this challenging situation, we need to ask what it is we are trying to achieve here, and how best to balance potential benefits with potential harm. PMID- 27190392 TI - Con: Nutritional vitamin D replacement in chronic kidney disease and end-stage renal disease. AB - Insufficiency of 25-hydroxyvitamin D [25(OH)D] is highly prevalent among patients with chronic kidney disease (CKD) or end-stage renal disease (ESRD) and is a critical component in the pathogenesis of secondary hyperparathyroidism. Accordingly, current National Kidney Foundation-Kidney Disease Outcomes Quality Initiative and Kidney Disease: Improving Global Outcomes guidelines recommend the correction of hypovitaminosis D through nutritional vitamin D replacement as a first-step therapeutic approach targeting secondary hyperparathyroidism. In this Polar Views debate, we summarize the existing evidence, aiming to defend the position that nutritional vitamin D replacement is not evidence-based and should not be applied to patients with CKD. This position is supported by the following: (i) our meta-analysis of randomized controlled trials shows that whereas nutritional vitamin D significantly increases serum 25(OH)D levels relative to placebo, there is no evidence either in predialysis CKD or in ESRD that parathyroid hormone (PTH) is lowered; (ii) on the other hand, in randomized head to-head comparisons, nutritional vitamin D is shown to be inferior to activated vitamin D analogs in reducing PTH levels; (iii) nutritional vitamin D is reported to exert minimal to no beneficial actions in a series of surrogate risk factors, including aortic stiffness, left ventricular mass index (LVMI), epoetin utilization and immune function among others; and (iv) there is no evidence to support a benefit of nutritional vitamin D on survival and other 'hard' clinical outcomes. Whereas nutritional vitamin D replacement may restore 25(OH)D concentration to near normal, the real target of treating vitamin D insufficiency is to treat secondary hyperparathyroidism, which is untouched by nutritional vitamin D. Furthermore, the pleotropic benefits of nutritional vitamin D remain to be proven. Thus, there is little, if any, benefit of nutritional vitamin D replacement in CKD. PMID- 27190393 TI - Opponent's comments. PMID- 27190394 TI - Moderator's view: Vitamin D deficiency treatment in advanced chronic kidney disease: a close look at the emperor's clothes. AB - Two recent vitamin D supplementation (ergocalciferol) trials in stage G5D CKD patients with vitamin D insufficiency showed that this sterol effectively increases serum 25-hydroxyvitamin D [25(OH)D] but fails to modify serum PTH and other clinical outcomes. The Pro side of this polar view emphasizes that the duration of these studies was too short to allow sensible analyses based on a clinical endpoint. Furthermore, he notes that in the second study, the use of active forms of vitamin D, phosphate binders and cinacalcet could have hindered appreciation of the effect of ergocalciferol supplementation per se The Con side produces an updated meta-analysis showing that inactive vitamin D forms largely fail to reduce serum PTH and affect various relevant endpoints, including muscle strength, functional capacity, quality of life and hospitalization. Studies suggesting an effect of inactive vitamin D forms in advanced CKD are either very small and mainly based on sequential, uncontrolled observations or inherently weak, simple pre/post studies. No biological or clinical evidence exists that 25(OH)D may exert meaningful effects in CKD patients who are being treated with active forms of vitamin D. Careful a etiologic studies based on the omics sciences, i.e. precise pathophysiological profiling of individual CKD patients followed by consequential, well-targeted intervention(s) in the precision medicine scenario, will likely provide a definitive answer to the lingering question of whether inactive vitamin D forms may have biological effects beyond those produced by their proximate metabolite 1,25-dihydroxyvitamin D3. PMID- 27190396 TI - Molecular regulation of the renin-angiotensin system in haemodialysis patients. PMID- 27190397 TI - A study of correlation of angioarchitecture of intracranial blood vessels with difficulty during endovascular coiling of aneurysms. AB - OBJECTIVE: The duration and complications of coiling are dependent on several factors. These include experience with the armamentarium and the expertise of the operator. Also, the angioarchitecture of the blood vessel can play an important role in the duration of the procedure and outcome. METHODS: 41 patients underwent endovascular coiling. The angioarchitecture of the vessels in terms of the course of the blood vessels from the arch of the aorta to the aneurysm, and the angles between the arch and its branches, between the parent and feeding arteries, and between the feeding artery and the aneurysm were measured. During coiling, duration, attempts, complications, and outcome were recorded. A correlation was made between angioarchitecture and difficulty during coiling. RESULTS: Based on number of attempts of coiling, two groups were defined. In group I, 26 patients underwent a single attempt with a mean duration of 61 min and in group II, 15 patients had more than one attempt with a mean duration of 98 min. The mean angle between the arch and its branches, between the internal carotid artery and the anterior cerebral artery, and between the anterior communicating artery and the aneurysm was more acute in group II compared with group I. Spearman's correlation suggested that as the angle at different vessel levels decreased, duration, attempt, and complications increased, and vice versa. CONCLUSIONS: Angioarchitecture analysis revealed that the sharper the angle (acute angle) between various vessels, the greater the difficulty in negotiating a microcatheter through the vessels and the more complications, duration, number of attempts, and poor outcome. We therefore feel that angioarchitecture analysis should be done carefully in all patients in whom the decision to undergo coiling is taken. PMID- 27190398 TI - Mechanical thrombectomy with the ERIC retrieval device: initial experience. AB - OBJECTIVE: To report our experience with the Embolus Retriever with Interlinked Cage (ERIC) stentriever for use in mechanical endovascular thrombectomy (MET). METHODS: Thirty-four consecutive patients with acute stroke (21 men and 13 women; median age 66 years) determined appropriate for MET were treated with ERIC and prospectively included over a 6-month period at three different centers. The ERIC device differs from typical stentrievers in that it is designed with a series of interlinked adjustable nitinol cages that allow for fast thrombus capture, integration, and withdrawal. The evaluated endpoints were successful revascularization (Thrombolysis in Cerebral Infarction (TICI) 2b-3) and good clinical outcomes at 3 months (modified Rankin Scale (mRS) 0-2). RESULTS: Locations of the occlusions included the middle cerebral artery (13 patients), terminal carotid artery (11 patients), basilar artery (1 patient), and tandem occlusions (9 patients). IV thrombolysis was performed in 20/34 (58.8%) patients. Median times from symptom onset to recanalization and from puncture to recanalization were 325.5 min (180-557) and 78.5 min (14-183), respectively. Used as the first-line device, ERIC achieved a successful recanalization in 20/24 (83.3%) patients. Successful recanalization was associated with lower National Institutes of Health Stroke Scale scores at 24 h (8+/-6.5 vs 21.5+/-2.1; p=0.008) and lower mRS at 3 months (2.7+/-2.1 vs 5.3+/-1.1; p=0.04). Three procedural complications and four asymptomatic hemorrhages were recorded. Good clinical outcomes at 3 months were seen in 15/31 (48.4%) patients. CONCLUSIONS: The ERIC device is an innovative stentriever allowing fast, effective, and safe MET. PMID- 27190399 TI - Time-to-Pregnancy Associated With Couples' Use of Tobacco Products. AB - INTRODUCTION: Previous studies suggest female smoking increases time-to-pregnancy (TTP), a couple-dependent reproductive outcome, while associations with male smoking are more ambiguous. Furthermore, despite small increases in smokeless tobacco use in the United States, no prior study has evaluated TTP among smokeless tobacco users. METHODS: Using population-based sampling in 16 counties in Michigan and Texas, 501 couples discontinuing contraception to become pregnant were followed until positive pregnancy test or 12 months of trying. Participants were interviewed on lifetime and current cigarette, cigar, and chew/snuff (smokeless) use and provided blood samples for quantification of heavy metals and cotinine. Fecundability odds ratios (FORs) and 95% confidence intervals (95% CIs) were estimated, adjusted for demographics/lifestyle. FORs less than 1 reflect longer TTP. RESULTS: Eleven percentage of females and 15% of males smoked cigarettes. Among men, 14% smoked cigars, 9% used snuff, and 2% used chew. Compared with never tobacco users, male (FOR: 0.41, 95% CI: 0.24, 0.68) and female (FOR: 0.53, 95% CI: 0.33, 0.85) smoking were individually associated with longer TTP; males' smoking remained significant (FOR: 0.46, 95% CI: 0.27, 0.79) when modeling partners together. Cadmium levels were higher in smokers than smokeless tobacco and never users; adjusting for cadmium attenuated the cigarette TTP association, particularly among women. TTP was shorter among smokeless tobacco users relative to smokers (FOR: 2.86, 95% CI: 1.47, 5.57). CONCLUSIONS: Compared with never users, smokeless tobacco did not alter TTP in our cohort; however, TTP was shorter compared with smokers. We observed longer TTP in male and female smokers; cadmium may partially contribute. IMPLICATIONS: Both partners' preconception smoking contributed to longer TTP, highlighting the importance of both partners' lifestyles in healthy reproduction and underscores the need for couple-based preconception guidance. The male's contribution is a new finding. Higher cadmium levels may partially contribute to longer TTP in smokers, particularly among females. Though we do not observe longer TTP among a small sample of smokeless tobacco users compared with never tobacco users, we observe shorter TTP compared with smokers. Further work is needed to more thoroughly delineate the relationship between smokeless tobacco use and TTP and possible mechanisms of tobacco use's effects on reproduction. PMID- 27190400 TI - Fetal Exposure to Carcinogens With Tobacco Use in Pregnancy: Phase 1 MAW Study Findings. AB - INTRODUCTION: The high prevalence of smoking and smokeless tobacco (ST) use during pregnancy in Alaska Native (AN) women is concerning due to the detrimental effects of these products to the mother and the developing fetus. We sought to correlate maternal cotinine levels with fetal exposure to a tobacco-specific carcinogen to incorporate in a biomarker feedback intervention to motivate tobacco cessation during pregnancy. METHODS: Demographic and tobacco use data were collected from a convenience sample of pregnant AN smokers, ST users, and non-users. Maternal and neonatal urine were collected at delivery. Maternal urine cotinine and neonatal urine total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL, a tobacco-specific carcinogen) levels in smokers and ST users were analyzed and their correlations determined by Spearman correlation coefficients. RESULTS: During 2012-2014, we enrolled 64 non-users, 54 smokers, and 30 ST (20 homemade iqmik; 10 commercial ST) users (n = 148). Analyses of paired maternal infant urine samples obtained for 36 smokers demonstrated a moderate to strong correlation (r = 0.73, P < .001) between maternal cotinine and infant NNAL levels. The correlation was not significant for 25 iqmik users (r = 0.36, P = .17) or 9 commercial ST users (r = 0.60, P = .09). No analysis was conducted for 55 non-users with cotinine and NNAL levels < limits of quantification. CONCLUSIONS: There is a moderate to strong correlation between maternal smoking and fetal exposure to the tobacco-specific carcinogen NNAL. IMPLICATIONS: The correlation between maternal smoking and fetal carcinogen exposure may provide an education tool to help motivate smoking cessation among pregnant AN women. Further investigation is warranted to determine correlations between maternal commercial ST and iqmik use and neonatal NNAL. PMID- 27190401 TI - Exposure to Secondhand Smoke Among Nonsmokers in New York City in the Context of Recent Tobacco Control Policies: Current Status, Changes Over the Past Decade, and National Comparisons. AB - INTRODUCTION: Exposure to secondhand smoke is hazardous and can cause cancer, coronary heart disease, and birth defects. New York City (NYC) and other jurisdictions have established smoke-free air laws in the past 10-15 years. METHODS: NYC Health and Nutrition Examination Survey (HANES) 2013-2014 was a population-based survey of NYC residents, aged 20 years and older, in which biospecimens were collected and cotinine levels were measured. Secondhand smoke exposure was assessed by demographics and risk factors and compared with that from NYC HANES 2004 and national HANES. RESULTS: More than a third (37.1%, 95% confidence interval [CI] = 33.3%-41.2%) of nonsmoking adult New Yorkers were exposed to secondhand smoke, defined as a cotinine level of 0.05-10ng/mL. This was significantly lower than in 2004 NYC HANES, when 56.7% (95% CI = 53.6%-59.7%) of nonsmokers were exposed to secondhand smoke, but was greater than the proportion of adults exposed nationwide, as measured by national HANES (24.4%, 95% CI = 22.0%-26.9% in 2011-2012). Men, non-Hispanic blacks, adults aged 20-39, those with less education, and those living in high-poverty neighborhoods were more likely to be exposed. CONCLUSIONS: There has been a large decrease in secondhand smoke exposure in NYC, although disparities persist. The decrease may be the result of successful policies to limit exposure to secondhand smoke in public places and of smokers smoking fewer cigarettes per day. Yet NYC residents still experience more secondhand smoke exposure than US residents overall. Possible explanations include multiunit housing, greater population density, and pedestrian exposure. IMPLICATIONS: Measuring exposure to secondhand smoke can be difficult, and few studies have monitored changes over time. This study uses serum cotinine, a nicotine metabolite, from a local population-based examination survey, the NYC HANES 2013-2014, to examine exposure to secondhand smoke in an urban area that has implemented stringent antismoking laws. Comparison with NYC HANES conducted 10 years ago allows for an assessment of changes in the last decade in the context of municipal tobacco control policies. Results may be helpful to jurisdictions considering implementing similar tobacco control policies. PMID- 27190402 TI - Tobacco Use and 12-Month Suicidality Among Adults in the United States. AB - INTRODUCTION: To examine how 12-month prevalences of suicidality vary by tobacco use. METHODS: Data were from 325 800 adults who participated in the 2008-2014 National Survey on Drug Use and Health. Descriptive analyses and multivariable multinomial logistic regression models were applied. RESULTS: Among adults aged 18 or older in the United States during 2008-2014, 27.4% (annual average, standard error [SE] = 0.14%) were never tobacco users, 38.8% (SE = 0.17%) were former tobacco users, 5.9% (SE = 0.07%) were past-year users of other types of tobacco (non-cigarette), 20.2% (SE = 0.13%) were past-year cigarette-only users, and 7.7% (SE = 0.07%) were past-year users of cigarettes plus other types of tobacco; 2.6% (SE = 0.04%) had suicidal ideation only, 0.7% (SE = 0.02%) had suicidal ideation and suicide plan only, and 0.5% (SE = 0.02%) attempted suicide. After controlling for covariates, compared with never tobacco users, past-year users of cigarettes plus other types of tobacco were at elevated risk of all examined suicidality outcomes (adjusted relative risks [ARRs] = 1.2-1.7), and past-year cigarette-only users were at higher risk of suicide attempt (ARR = 1.4). Early age of first tobacco use was associated with higher risk of suicidal ideation and suicide plan among former tobacco users, past-year tobacco users, and past-year cigarette users (ARRs = 1.2-1.6). Among past-year tobacco users, frequencies of cigarette and cigar use were associated with suicide attempt (ARRs = 1.4-1.7). Nicotine dependence was associated with suicide attempt among past year cigarette users (ARR = 1.2). CONCLUSIONS: Tobacco use is associated with 12 month suicidality among adults. Patients who use tobacco should be assessed further for mental health status and suicide risk. IMPLICATIONS: Our results revealed that tobacco use is independently associated with the 12-month suicidality outcomes among adults and identified how the prevalences of 12-month suicidality outcomes vary by tobacco use status and use characteristics among adults. These results have important clinical implications. Future research should assess the effectiveness of tobacco use questions as simple screeners for more extensive assessment of mental health status and suicide risk. PMID- 27190403 TI - Prevalence and Correlates of the Belief That Electronic Cigarettes are a Lot Less Harmful Than Conventional Cigarettes Under the Different Regulatory Environments of Australia and the United Kingdom. AB - INTRODUCTION: The rapid rise in electronic cigarettes (ECs) globally has stimulated much debate about the relative risk and public health impact of this new emerging product category as compared to conventional cigarettes. The sale and marketing of ECs containing nicotine are banned in many countries (eg, Australia) but are allowed in others (eg, United Kingdom). This study examined prevalence and correlates of the belief that ECs are a lot less harmful than conventional cigarettes under the different regulatory environments in Australia (ie, more restrictive) and the United Kingdom (ie, less restrictive). METHODS: Australian and UK data from the 2013 survey of the International Tobacco Control Four-Country project were analyzed. RESULTS: More UK than Australian respondents (58.5% vs. 35.2%) believed that ECs are a lot less harmful than conventional cigarettes but more respondents in Australia than in the United Kingdom selected "Don't Know" (36.5% vs. 17.1%). The proportion that responded "A little less, equally or more harmful" did not differ between countries. Correlates of the belief that ECs are "A lot less harmful" differed between countries, while correlates of "Don't Know" response did not differ. CONCLUSIONS: Consistent with the less restrictive regulatory environment affecting the sale and marketing of ECs, smokers and recent ex-smokers in the United Kingdom were more likely to believe ECs were less harmful relative to conventional cigarettes compared to those in Australia. IMPLICATIONS: What this study adds: Among smokers and ex smokers, this study found that the belief that ECs are (a lot) less harmful than conventional cigarettes was considerably higher in the United Kingdom than in Australia in 2013. The finding is consistent with the less restrictive regulatory environment for ECs in the United Kingdom, suggesting that the regulatory framework for ECs adopted by a country can affect smokers' perceptions about the relative harmfulness of ECs, the group that stands to gain the most from having an accurate belief about the relative harms of ECs. PMID- 27190404 TI - Genital contact allergy: A diagnosis missed. AB - Genital allergy should be considered as a possible diagnosis in all patients with genital soreness or irritation for which no infection or dermatosis can be identified and in whom symptoms remain unchanged or worsen with treatment. It is an underreported and underdiagnosed condition as patients may not complain about symptoms in this area. Moreover, diagnosis and therapy may not often be conducted by a dermatologist or allergologist. Therefore, many cases of allergic diseases in the genital area remain undetected. PMID- 27190405 TI - Treatment seeking behaviour of STI clients in a tertiary care centre of North India: A cross sectional study. AB - OBJECTIVE: (1) To determine the treatment seeking behaviour of STI clients. (2) To ascertain the relationship of socio-demographic factors and sexual behaviours with the treatment seeking component in STI clients. METHODS: This cross sectional study was conducted in Department of Dermatology, Faculty of Medical Sciences, King George's Medical University, Lucknow, Uttar Pradesh. After obtaining approval from the Institutional Ethical Committee, the data collected daily from master register, STI/RTI patient wise register and counsellor's patient diary during the study period August 2013 to July 2015 was processed by Microsoft Excel program. The counsellor also recorded the source of information regarding STI Clinic. The information collected regarding bio-social characteristics, high risk sexual behaviours and source of knowledge about Suraksha clinic was analysed. RESULTS: Our results showed that literacy, male sex, urban residence and employment were some of the parameters which significantly improved the health seeking behaviour of STI clients. These variables were associated with higher odds for seeking treatment when adjusted for other variables. Similarly group with bisexual and homosexual behaviour had significantly lower odds for seeking treatment when adjusted for other variables. CONCLUSION/KEY MESSAGE: The optimal use of information, education and communication (IEC) techniques needs to be strengthened to further improve the utilization of STI clinic services at tertiary care teaching hospitals. PMID- 27190406 TI - Diagnostic accuracy of self-reported symptomatic assessment versus per speculum/per vaginal examination for the diagnosis of vaginal/cervical discharge and lower abdominal pain syndromes among female sex workers. AB - BACKGROUND: National AIDS Control Organization guidelines on enhanced syndromic case management of sexually transmitted infections (STIs) and reproductive tract infections (RTIs) require per speculum (P/S) and per vaginal (P/V) examinations for diagnosis of STIs. However, it is not known if the addition of P/S and P/V examinations to self-reported symptomatic assessment adds any value for the diagnosis of STI/RTI. OBJECTIVE: To assess the diagnostic accuracy of P/S and P/V examinations compared with self-reported symptomatic assessment in a cohort of female sex workers (FSWs). METHODS: We performed a cross-sectional study from August 2009 to June 2010, among 519 FSWs in Surat city, Gujarat, India. Symptomatic assessment for the presence or absence of vaginal/cervical discharge (VCD) or lower abdominal pain (LAP) was done using a self-administered questionnaire. After completion of the questionnaire, all participants underwent P/S and P/V examinations. Summary diagnostic accuracy measures were calculated. RESULTS: Five hundred and nineteen FSWs between the ages of 18-49 years participated in the study. The median age of participants was 31 years. The prevalence of VCD and LAP syndromes based on vaginal discharge, LAP, or both was 56%, 5,-10%, respectively. The sensitivity of P/S and P/V examinations depending on symptomatic assessment ranged from 47% to 76%. The specificity ranged from 73% to 93%. The positive predictive value ranged from 25% to 83%, and the negative predictive value ranged from 56% to 98%. CONCLUSION: Symptomatic assessment alone is not adequate for the diagnosis of VCD and LAP syndromes and can lead to a significant number of missed cases (36%). A P/S and P/V examinations is critical for assessment of VCD and LAP syndromes and subsequent treatment. PMID- 27190407 TI - Randomized questionnaire based cross-sectional research study on awareness of sexually transmitted diseases amongst the general population between those who completed their high school education and those who have not. AB - INTRODUCTION: Sexually transmitted diseases (STDs) are a very important health challenge for adolescents. Educational level, especially sex education in school, prevents the adolescents falling prey to these diseases. OBJECTIVE: To compare the awareness of STDs among general population with below and above high school qualification. MATERIALS AND METHODS: A simple randomized, cross-sectional, questionnaire based study on the awareness of STDs on out-patients and in patients of Saveetha Medical College and Hospital of 6 months duration was conducted. About 150 subjects participated in the study. RESULTS: About 77.8% of those who completed schooling had good awareness of STDs. Statistical analysis had shown the formal education to high school level is statistically significantP= 0.0068 (P < 0.05) in people falling prey to the STDs. CONCLUSION: The initiation of formal education about sex education at the school level can improve the present status and lead to better prevention of STDs. PMID- 27190408 TI - Predictors of unsafe sexual behavior among people living with human immunodeficiency virus/AIDS attending antiretroviral therapy center in Western India. AB - BACKGROUND: As more and more people with human immunodeficiency virus (HIV) live longer and healthier lives because of antiretroviral therapy (ART), an increasing number of sexual transmissions of HIV may arise from these people living with HIV/AIDS (PLWHA). Hence, this study is conducted to assess the predictors of unsafe sexual behavior among PLWHA on ART in Western India. MATERIALS AND METHODS: The current cross-sectional study was carried out among 175 PLWHAs attending ART center of a Tertiary Care Hospital in Western India. Unsafe sex was defined as inconsistent and/or incorrect condom use. A total of 39 variables from four domains viz., sociodemographic, relationship-related, medical and psycho social factors were studied for their relationship to unsafe sexual behavior. The variables found to be significantly associated with unsafe sex practices in bivariate analysis were explored by multivariate analysis using multiple logistic regression in SPSS 17.0 version. RESULTS: Fifty-eight percentage of PLWHAs were practicing unsafe sex. 15 out of total 39 variables showed significant association in bivariate analysis. Finally, 11 of them showed significant association in multivariate analysis. Young age group, illiteracy, lack of counseling, misbeliefs about condom use, nondisclosure to spouse and lack of partner communication were the major factors found to be independently associated with unsafe sex in multivariate analysis. CONCLUSION: Appropriate interventions like need-based counseling are required to address risk factors associated with unsafe sex. PMID- 27190409 TI - Efficacy of syndromic management measured as symptomatic improvement in females with vaginal discharge syndrome. AB - BACKGROUND: In spite of a few shortcomings such as over diagnosis and over treatment, syndromic management is a recommended practice in India for sexually transmitted infections (STIs). This study tries to find out the efficacy of syndromic management measured as symptomatic improvement in females with vaginal discharge syndrome. OBJECTIVE: The objective of the study is to find out the effectiveness of syndromic management in terms of symptomatic improvement among females with vaginal discharge syndrome. MATERIALS AND METHODS: A longitudinal study was conducted in Gynecology Department of Tertiary Care Hospital including 180 symptomatic females having vaginal discharge syndrome. Demographic profile, presenting complaints, menstrual history, obstetric history, partner history, and contraceptive history were noted. This was followed by clinical examination and specimen collection for laboratory tests and blood tests to find out type of STI including viral STI such as human immunodeficiency virus (HIV), herpes simplex virus (HSV), and hepatitis B surface antigen (HBsAg). Treatment was given according to syndromic management on the same day. All the participants were asked to come for follow-up after 15 days and their improvement in symptoms was noted as complete improvement, some improvement or no improvement on a five point scale. RESULTS: 63.9% cases showed complete improvement, while 36.1% showed some improvement. None of the patients was without any improvement. Vaginal discharge syndrome was most common between 20 and 30 years (43.4%), and 67.8% of symptomatic females with vaginal discharge syndrome belonged to the lower socioeconomic group. HSV infection was the most common (15%) associated viral infection with vaginal discharge syndrome, while hepatitis B infection was the least common (0.5%). HIV was reactive in 2.8% cases only. CONCLUSION: Syndromic management was found to be effective in relieving symptoms in most of the cases of vaginal discharge syndrome. PMID- 27190410 TI - Time trends of seroepidemiology of hepatitis C virus and hepatitis B virus coinfection in human immunodeficiency virus-infected patients in a Super Specialty Hospital in New Delhi, India: 2012-2014. AB - BACKGROUND: Hepatitis viruses and human immunodeficiency virus (HIV) coinfection is a major cause of liver diseases worldwide. High prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) in Asia makes it important to understand HBV and HCV coinfection with HIV in this part of the globe. This study was done with the aim of assessing the time trends of seroepidemiology of HBV and HCV coinfection in HIV patients over the last 3 years. MATERIALS AND METHODS: Year wise retrospective analysis of data between January 2012 and December 2014 was done. RESULTS: The prevalence of HIV infection among 0-20 years and >60 years age group decreased over the last 3 years (2012-2014), 8.4%, 6.4%, and 3.1% and 3.6%, 3.8%, and 1.5%, respectively. While increasing prevalence was seen among 21-40 years age group, 57.8%, 60.2%, and 67.1%, respectively in 2012, 2013, and 2014. There was no significant relationship between age/gender and HBV/HCV seropositivity among HIV-positive patients. The risk of acquiring HBV infection was more in HIV-positive patients who were >60 years of age (odds ratio = 3.3182; 95% confidence interval: 0.3669-30.005). The prevalence of HCV seropositivity is less in HIV-positive patients as only one case was anti-HCV antibody positive in last 3 years who was a male patient in the age group 21-40 years. A declining trend was observed for HIV positive cases over 2012-2014 while no significant trend change is seen in HBV/HCV seropositivity among HIV patients from 2012 to 2104. CONCLUSION: It is recommended to screen HIV patients routinely for concurrent HBV/HCV infection as hepatotropic viruses with HIV increase the risk of liver mortalities. PMID- 27190411 TI - Clinical manifestations and outcome of patients with human immunodeficiency virus infection at tertiary care teaching hospital. AB - BACKGROUND: AIDS has become chronic illness which is well treated with antiretroviral therapy and management of opportunistic infections (OIs). AIMS AND OBJECTIVES: The study clinical profile and outcome of human immunodeficiency virus (HIV) seropositive patients. MATERIALS AND METHODS: This was retrospective observational study carried out over a period of 1 year (January 2011-December 2011). All HIV patients admitted in medicine ward, and ICU were enrolled. Statistical analysis was performed using SSPE statistical software trial version 11. The P< 0.05 was considered as statistically significant. RESULTS: Of total 111 patients with a diagnosis of HIV/AIDS, 75 (67.56%) were male and 36 (32.43%) were female patients. A total 52 (46.84%) patients presented with respiratory manifestations, of them 23 (44.23%) had pulmonary tuberculosis (TB), 6 (11.53%) had tubercular effusion, and 3 (5.76%) had Pneumocystis jirovecii pneumonia. Respiratory manifestations including pulmonary TB were the most common presentation (P< 0.001). Total 27 (24.32%) patients were presented with the neurological manifestation of them 8 (29.62%) had a cerebro-vascular accident, 5 (18.51%) had cryptococcal meningitis, 4 (14.81%) had tubercular meningitis, and 1 (3.70%) had progressive multifocal leukoencephalopathy. Total 12 (38.70%) had acute gastroenteritis 6 (19.35%) had oral candidiasis, 8 (25%) had general tonic clonic seizure and 7 (21.87%) had pyrexia of unknown origin, 6 (18.75%) had septicemia, 6 (18.75%) had acute renal failure, and 6 (94.11%) had anemia. A total 11 (9.90%) patients succumbed. CONCLUSIONS: Overall respiratory manifestations were the common presentation in a present cohort of HIV seropositive patients and TB was the most common OI and the cerebrovascular accident was the most common neurological manifestation. PMID- 27190413 TI - Performance of the prevention of parent to child transmission program: A decadal trend from rural Maharashtra, India. AB - BACKGROUND: Human immunodeficiency virus (HIV) infection is widely spread across the state of Maharashtra with high prevalence among antenatal women. AIMS: To assess the effectiveness of prevention of parent to child transmission (PPTCT) services in rural Tertiary Health Care Centre of Western Maharashtra, India and to address the weaknesses in functioning of PPTCT services. MATERIALS AND METHODS: A cross-sectional study was conducted at Integrated Counselling and Testing Centre (ICTC) of a rural tertiary health center located in rural area of Western Maharashtra over a period of 10 years from 2003 to 2012. A total of 32,575 pregnant women were included as study subjects and data were collected as per the indicators of PPTCT by viewing the retrospective PPTCT records. The data were analyzed over the period of 10 years for the outcome of PPTCT services. The trend of PPTCT indicators over a decade were analyzed by using Chi-square test. RESULTS: The seroprevalence of HIV infection among pregnant women was 2% in 2003 which decreased to 0.2% by 2012. The proportions of women counseled and HIV tested were 88.9% and 100%, respectively in 2003 and pretest counseling trend was steadily increased to 100% by 2012; however; HIV testing trend remained 100% throughout 10 years. Posttest counseling trend ranges from 89.6% to 99.9% whereas trend of HIV testing among partners has been fluctuating from 25% to 100%. The proportional trend of HIV-positive mothers delivered in a tertiary care hospital ranges from 60% to 100%. The proportions of pair receiving prophylaxis Nevirapine has been increased from 83.8% to 100% by 2009, but thereafter decreased to 83.3% by 2012. The overall HIV positivity among babies after 18 months of follow-up was 21%. CONCLUSION: HIV seroprevalence among the pregnant population is steadily declining. More and more women are availing the facilities of ICTC centers. Intensive health education and availability of diagnostic and therapeutic services in rural health center have reduced the burden of HIV/AIDS problem in the rural community. PMID- 27190412 TI - High-risk sexual behavior among people living with HIV/AIDS attending tertiary care hospitals in district of Northern India. AB - CONTEXT: Prevention with a positive approach has been advocated as one of the main strategies to diminish the new instances of HIV and the target are those who are engaged in high-risk sexual behavior. Therefore, understanding the risky behaviors of the HIV-infected individual is important. AIMS: This study aimed to assess the prevalence and the predictors of high-risk sexual behavior among people living with HIV/AIDS (PLHA). SETTINGS AND DESIGN: A hospital-based cross sectional study was conducted at antiretroviral therapy centers of two tertiary care hospitals in Lucknow. MATERIALS AND METHODS: A total of 322 HIV-positive patients were interviewed about their sexual behaviors during last 3 months using a pretested questionnaire. STATISTICAL ANALYSIS USED: Probability (p) was calculated to test for statistical significance at 5% level of significance. Association between risk factors and high-risk sexual behavior was determined using bivariate analysis followed by multivariate logistic regression. RESULTS: Prevalence of high-risk sexual behavior was 24.5%. Of these patients, multiple sexual partners were reported by 67.3% whereas about 46.9% were engaged in unprotected sex. Multivariate logistic regression analysis revealed that high risk sexual behavior was significantly associated with nonsupporting attitude of spouse (odds ratio [OR]: 18; 95% confidence interval [CI]: 1.4-225.5; P = 0.02) and alcohol consumption (OR: 9.3; 95% CI: 2.4-35.4; P = 0.001). CONCLUSIONS: Specific intervention addressing alcohol consumption and encouragement of spouse and family support should be integrated in the routine HIV/AIDS care and treatment apart from HIV transmission and prevention knowledge. PMID- 27190414 TI - Is it time to bring the "Parent" into the prevention of parent to child transmission programs in India? A study of trends over a 10-year period in a prevention of parent to child transmission clinic in India. AB - OBJECTIVES: The present study evaluated the changes in serology and human immunodeficiency virus (HIV) testing behaviors over a 10-year period in a center in India. METHODS: We used clinical data collected at the antenatal clinic from 2002 to 2011. The key outcomes were: (1) Proportion of women who opted for HIV test and those who tested positive; (2) proportion of male partners who came in for HIV test and those who tested positive; and (3) proportion of women who opted for continuation of pregnancy or for medical termination of pregnancy. RESULTS: We tested 11,452 women for HIV over the 10-year period from 2002 to 2011. The proportion of women who opted for HIV testing was 72.0% (95% confidence interval [CI]: 70.7-73.4%). The acceptance of test increased from 35.9% (95% CI: 31.7 40.4%) in 2002 to the peak of 82.6% (95% CI: 78.6-86.8%) in 2009 (P < 0.001). The overall HIV prevalence over the decade was 0.70% (95% CI: 0.55-0.87%). The prevalence high at 1.11% (95% CI: 0.23-3.24%) in 2002 and reduced to 0.37% (95% CI: 0.12-0.87%) in 2011 (P < 0.001). Only 0.57% of male partners tested for HIV over this time period. CONCLUSION: Strategies to improve acceptance of testing in pregnant women should be included in the Indian guidelines. The male partners do not get tested. Thus, this component needs to be strengthened - by targeted interventions for male spouses - to make the program more effective. PMID- 27190415 TI - Fox-Fordyce disease of the vulva. AB - Fox-Fordyce disease is a rare, chronic skin disorder which affects the apocrine areas. This disease is due to the obstruction of the apocrine sweat duct. Extragenital regions are commonly affected than the genital region. We, herein, report a case of Fox-Fordyce in a female, with onset in the fifth decade and involving only the genital region. PMID- 27190416 TI - Kurthia gibsonii as a sexually transmitted zoonosis: From a neglected condition during World War II to a recent warning for sexually transmitted disease units. AB - CONTEXT: Zoonotic sexual transmission. AIMS: Identification of unknown microorganisms causing sexually transmitted zoonotic infection was a common effort of clinicians and the laboratory. SETTINGS AND DESIGN: A male patient had recurring urethritis and balanitis after having repeated unprotected penetrative sexual intercourse with female piglets. He claimed allergy to metals and plastics. Routine microbiological tests were carried out. MATERIALS AND METHODS: Specimens from the urethra, glans, rectum, throat, urine, and blood were cultured. Subsequently, isolates were tested for their biochemical activity and antibiotic susceptibility. RESULTS: Kurthia gibsonii was isolated from both urethra and glans. No other concomitant infection was detected. The patient was cured with oral cefuroxime for 15 days and topical gentamicin cream for 2 months. CONCLUSION: This is the first reported zoophilic infection by Kurthia spp. Fecal contamination of animals' genital tract was the possible source of infection. Immune disturbance of the patient might predispose to opportunistic Kurthia infection. PMID- 27190417 TI - Crusted Scabies: Presenting as erythroderma in a human immunodeficiency virus seropositive patient. AB - Crusted scabies is a rare manifestation of scabies characterized by uncontrolled proliferation of mites in the skin. It is common in patients with sensory neuropathy, mentally retarded persons and in patients who are immunosuppressed. Further, crusted scabies can rarely present as erythroderma (<0.5% cases) necessitating a high index of suspicion for its diagnosis. Because of its rare occurrence, we are reporting a case of crusted scabies presenting as erythroderma, in a human immunodeficiency virus seropositive patient. PMID- 27190419 TI - Gingival mass in acquired immune deficiency syndrome patient: An unusual manifestation. AB - Non-Hodgkin's lymphoma (NHL) is designated as an acquired immune deficiency syndrome defining condition. Although uncommon, it is essential to be wary of this neoplasm since intraoral manifestations may be the first clinical manifestation of HIV disease. The gingiva is one of the rarest intraoral sites with a prevalence of 0.6%. Careful evaluation of patients presenting with solitary atypical gingival mass can lead to early detection of HIV disease. Here, we report a case of NHL manifesting as a gingival mass in a 45-year-old HIV positive female patient. PMID- 27190418 TI - Cardiovascular syphilis complicated by Lower thoracic and upper abdominal aneurysm - A rare case report. AB - A 50-year-old male presented with left lower abdominal pain, visible pulsation below xiphoid process, and tenderness in the left iliac fossa for the past 10 days. Chest X-ray revealed blunting of left cardiophrenic angle. Echocardiogram revealed descending thoracic aortic pseudoaneurysm. Contrast-enhanced computed tomography of the chest and abdomen revealed dissecting aneurysm of lower thoracic and upper abdominal aorta. Thoracoabdominal aortogram revealed erosion of D12 vertebra and infected aneurysm of adjacent thoracoabdominal aorta. Serum venereal disease research laboratory assay was positive in 1:4 dilution Treponema pallidum hemagglutination assay was positive. The patient was treated with Injection procaine penicillin for 20 days undercover of steroids. Cerebrospinal fluid analysis was normal. Aortic aneurysm repair with reconstruction was done. Histopathology was in favor of syphilitic etiology. This case is being presented as descending thoracic and upper abdominal aortic aneurysm due to syphilis complicated by dissection and erosion of vertebral body is rare and has not been reported nowadays to the best of our knowledge. PMID- 27190420 TI - Erythema elevatum diutinum in acquired immune deficiency syndrome: Can it be an immune reconstitution inflammatory syndrome? AB - A 47-year-old male with acquired immune deficiency syndrome (AIDS) presented with multiple hyperpigmented papules and nodules on both ankles, dorsum of bilateral feet and soles. It was associated with mild itching and pain. The patient was diagnosed with human immunodeficiency virus (HIV) in 2007. First-line antiretroviral therapy (ART) was started in 2009 to which he responded initially. He was shifted to second-line ART 11 months ago in March 2015 due to treatment failure as suggested by CD4 count of 50 cells/mm(3). The present skin lesions started 2 months after the initiation of second-line ART. Differential diagnoses considered were Kaposi's sarcoma and immune reconstitution inflammatory syndrome (IRIS) related infections, but biopsy was suggestive of erythema elevatum diutinum (EED). Patient was started on oral dapsone 100 mg/day and increased to 200 mg/day to which he is responding gradually. In the present case, appearance of the lesions after initiation of second-line ART coupled with increase in CD4 count and decrease of viral load below undetectable level suggest that EED could be an IRIS. PMID- 27190421 TI - Sildenafil: A rare cause of erythema multiforme. AB - Erythema multiforme (EM) is an acute self-limiting mucocutaneous condition of uncertain etiopathogenesis. The most common precipitating factors are herpes simplex virus infection, mycoplasma infection, drugs, and vaccination. We report a case of EM following sildenafil used for loss of libido. EM induced by sildenafil has not been reported so far. PMID- 27190422 TI - Failure to achieve reduction in the incidence of human immunodeficiency virus among men who have sex with men: A worrisome global concern. PMID- 27190423 TI - Anti-human immunodeficiency virus serology status and pre- and post-test counseling: A note. PMID- 27190425 TI - A case of mistaken identity. PMID- 27190424 TI - Syphilis incognito: Resurgence of the covert devil. PMID- 27190426 TI - Seroprevalence of hepatitis B and syphilis co-infection in human immunodeficiency virus-positive antiretroviral therapy attendees and human immunodeficiency virus negative sexually transmitted infection attendees. PMID- 27190427 TI - Co-infection of hepatitis B virus and hepatitis C virus with human immunodeficiency virus infection: A cross-sectional study. PMID- 27190428 TI - Viva questions for postgraduate. PMID- 27190429 TI - MUC1 Immunohistochemical Expression as a Prognostic Factor in Gastric Cancer: Meta-Analysis. AB - MUC1, a member of the mucin family, is expressed in tumors of various human organs and may function as an antiadhesion molecule that inhibits cell-to-cell adhesion, inducing tumor metastasis, and served as a potential biomarker of tumor progression in early gastric cancer. However, its prognostic significance in gastric cancer is still in dispute. We performed a meta-analysis to evaluate the relationship between MUC1 expression and prognosis of gastric cancer. A total of ten eligible studies with 834 cases and 548 controls were included. MUC1 positive cases were highly positive in intestinal-type carcinomas (OR = 1.76, 95% CI: 1.27 2.44, P = 0.0008 fixed-effect), higher rate of vascular invasion (OR = 1.64, 95% CI: 1.13-2.39, P = 0.009 fixed-effect), and lymph node metastasis (OR = 2.10, 95% CI: 1.20-3.67, P = 0.01 random-effect), as well as lower 5-year survival rate (HR = 0.27, 95% CI: 0.11-0.66, P = 0.004 random-effect). However, the presence of MUC1 was not associated with gender, tumor size, histologic differentiation, and clinical stage. In summary, MUC1 is a prognostic factor in gastric cancer, which acts as a marker of poor outcome in patients with gastric cancer. Further clinical studies are needed to confirm the role of MUC1 in clinical practice. PMID- 27190431 TI - The thermic response to food intake in persons with thoracic spinal cord injury. AB - [Purpose] To investigate the influence of the level of spinal cord injury on the thermic effect of food intake (TEF) in persons with thoracic spinal cord injury. [Subjects and Methods] Seven male subjects with spinal cord injury (SCI; age, 40 +/- 6 years) and six able-bodied subjects (AB; age, 37 +/- 8 years) volunteered to participate in the present study. The subjects consumed an identical test meal consisting of 7.9 kcal/kg of body weight. Energy expenditure and plasma norepinephrine concentrations were measured over a 3-hour period. [Results] The adjusted TEF at 60 min was almost the same among the three groups [AB, SCI with high thoracic cord (T5-6) injury (HSCI), and SCI with low thoracic cord (T9-12) injury (LSCI)]. Although the LSCI group had almost the same adjusted TEF at 120 min as the AB group, the adjusted TEF at 120 min of the HSCI group was significantly lower than that of the AB group. The changes in plasma norepinephrine concentration and heart rate in response to food intake were similar among the three groups. [Conclusion] SCI at the T5-6 level results in a lower TEF due to sympathetic decentralization. PMID- 27190430 TI - Efficacy of kinesio tape application on pain and muscle strength in patients with myofascial pain syndrome: a placebo-controlled trial. AB - [Purpose] The purpose of this study was to determine the short- and mid-term effects of Kinesio taping on the trapezius muscle in individuals with myofascial pain syndrome. [Subjects and Methods] Thirty-seven patients with active upper trapezius myofascial trigger points were randomly divided to 2 groups: group 1 received Kinesio taping for the upper trapezius muscle, and group 2 received a sham Kinesio taping application. Neck pain (Visual Analog Scale and pressure algometry) and trapezius muscle strength data were collected at baseline, immediately after Kinesio taping application, and at one month follow-up. [Results] The mean changes in Visual Analog Scale scores were significantly different between groups at T2 and T1, with less pain in group 1. The mean changes in algometry scores were significantly different between groups at T3 compared with T2 in favor of group 1. The mean changes in trapezius muscle strength were significantly different between the groups at T2 compared with T1 in favor of group 1. [Conclusion] Patients with myofascial pain syndrome receiving an application of Kinesio taping exhibited statistically significant improvements in pain and upper trapezius muscle strength. PMID- 27190432 TI - Differences in the body pressure-related sensory changes between the floor and mattress in a static supine position for physiotherapy research: a randomized controlled pilot trial. AB - [Purpose] This study was performed to investigate the difference in body pressure related sensory changes between the floor and mattress in a static supine position for physiotherapy research. [Subjects and Methods] To analyze body pressure, the Body Pressure Measurement System was used. Body pressure sensors were attached to mattresses and the floor beneath the subjects. The level of pain was evaluated using pain score tools before the static supine position was adopted, at 1, 5, 10, and 15 min, and in total for specific body points. [Results] In analysis of digitized images, there was no significant difference observed between floor and mattress body pressure values at the start position. However, the head pressure intensity was significantly higher than that of the other body parts. In analysis of pain scores, all body part pain scores except those for both legs were significantly higher for the floor than for the mattress. Furthermore, the pain scores of the floor group were significantly increased at minute 1 compared with those of the mattress group. [Conclusion] These results suggest that properties that change in a time-dependent manner and postural changes need to be carefully considered when applying physical therapy. PMID- 27190433 TI - Cellular fibronectin response to supervised moderate aerobic training in patients with type 2 diabetes. AB - [Purpose] Physical activity is one of the most pivotal targets for the prevention and management of vascular complications, especially endothelial dysfunctions. Cellular fibronectin is an endothelium-derived protein involved in subendothelial matrix assembly. Its plasma levels reflect matrix alterations and vessel wall destruction in patients with type II diabetes. This study investigated the influence of 12 weeks of supervised aerobic training on cellular fibronectin and its relationship with insulin resistance and body weight in type II diabetic subjects. [Subjects and Methods] This study included 50 men with type II diabetes who had a mean age of 48.8 +/- 14.6 years and were randomly divided into two groups: an aerobic exercise group (12 weeks, three 50 minutes sessions per week) and control group. To examine changes in cellular fibronectin, glycosylated hemoglobin, insulin resistance, fasting insulin, fasting blood sugar, and lipid profile, 5 ml of blood was taken from the brachial vein of patients before and 48 hours after completion of the exercise period and after 12 hours of fasting at rest. Data analysis was performed using the SPSS-16 software with the independent and paired t-tests. [Results] A significant decrease was observed in body mass index and body fat percentage in the experimental group. Compared with the control group, the aerobic exercise group showed a significant decrease in cellular fibronectin, glycosylated hemoglobin, insulin resistance, fasting insulin, fasting blood sugar, and lipid profile after 12 weeks of aerobic exercise. The change in cellular fibronectin showed positive significant correlation with body mass index, diabetic biomarkers, and physical activity level. [Conclusion] The results showed that supervised aerobic exercise as a stimulus can change the levels of cellular fibronectin as matrix metalloproteinase protein a long with improvement of insulin sensitivity and glycosylated hemoglobin in order to prevent cardiovascular diseases in men with diabetes. PMID- 27190434 TI - Strength and muscle activity of shoulder external rotation of subjects with and without scapular dyskinesis. AB - [Purpose] This study aimed to clarify the relationship between scapular dyskinesis and shoulder external rotation strength and muscle activity. [Subjects and Methods] Both shoulders of 20 healthy males were evaluated. They were classified into 19 normal, 8 subtly abnormal, and 13 obviously abnormal shoulders using the scapular dyskinesis test. Subtly abnormal shoulders were subsequently excluded from the analysis. Shoulder external rotation strength and muscle activity (infraspinatus, serratus anterior, upper, middle, and lower trapezius) were measured in 2 positions using a handheld dynamometer and surface electromyography while sitting in a chair with shoulder 0 degrees abduction and flexion (1st position), and while lying prone on the elbows with the shoulders elevated in the zero position (zero position). The strength ratio was calculated to quantify the change in strength between the positions (zero position / 1st position). [Results] In the obviously abnormal shoulder group, the strength in the 1st position was significantly stronger, the strength ratio was significantly smaller, and the serratus anterior in the zero position showed significantly lower activity than the normal shoulder group. [Conclusion] In shoulder external rotation in the zero position, in obviously abnormal shoulders, the serratus anterior is poorly recruited, weakening the shoulder external rotation strength. PMID- 27190435 TI - The effect of chiropractic techniques on the Cobb angle in idiopathic scoliosis arising in adolescence. AB - [Purpose] The purpose of this study was to examine whether chiropractic techniques would reduce the curvature of idiopathic scoliosis, which commonly occurs in elementary school children. [Subjects] The subjects of this study were 5 healthy elementary students who listened to an explanation of the study methods and purpose of the study and agreed to participate in the experiment. [Methods] The Cobb angle was measured by taking an X-ray (FCT-1, Dongmun, Goyangsi, Republic of Korea) taken from the rear, using X-ray film. The method of intervention this study used was application of chiropractic techniques. Spinal correction was carried out for 30 minutes per session, which included soft tissue massage, 3 times a week for 8 weeks. [Results] It was established that the Cobb angle was noticeably decreased after 4 weeks of the intervention. Post Hoc analysis revealed that the Cobb angle noticeably decreased after 4 weeks compared with the Cobb angle before the chiropractic techniques were applied. However, no significant difference in Cobb angle was evident after the fourth week. [Conclusion] This study demonstrated that chiropractic techniques can effectively reduce the Cobb angle within as little as 4 weeks. So, we can confirm that the chiropractic techniques were effective for reducing the curvature of idiopathic scoliosis. PMID- 27190436 TI - Effects of oculo-motor exercise, functional electrical stimulation and proprioceptive neuromuscular stimulation on visual perception of spatial neglect patients. AB - [Purpose] The purpose of this study was to identify the effects of oculo-motor exercise, functional electrical stimulation (FES), and proprioceptive neuromuscular facilitation (PNF) on the visual perception of spatial neglect patients. [Subjects and Methods] The subjects were randomly allocated to 3 groups: an oculo-motor exercise (OME) group, a FES with oculo-motor exercise (FOME) group, and a PNF with oculo-motor exercise (POME) group. The line bisection test (LBT), motor free visual test (MVPT), and Catherine Bergego Scale (CBS) were used to measure visual perception. These were performed 5 times per week for 6 weeks. [Results] The OME group and POME group showed significant improvements according to the LBT and MVPT results, but the FOME group showed no significant improvement. According to the CBS, all 3 groups showed significant improvements. The OME and POME groups showed improvement over the FOME group in the LBT and MVPT. However, there was no significant difference among the three groups according to the CBS. [Conclusion] These results indicate that oculo-motor exercise and PNF with oculo-motor exercise had more positive effects than FES with oculo-motor exercise on the visual perception of spatial neglect patients. PMID- 27190437 TI - An immunohistochemical study of the sciatic nerve in a rat knee immobilization model. AB - [Purpose] This study was performed to immunohistochemically evaluate changes in the periphery of the sciatic nerve in a rat model of knee immobilization, and to assess the effects of range of motion exercise. [Subjects and Methods] Twenty-one male rats were divided randomly into three groups: control (C), immobilized (I), and exercise (E group). Rats in the I and E groups had the right knee joint immobilized for 2 weeks. In the E group, range of motion exercise was also performed. After the experimental period, the periphery of the sciatic nerve was immunohistochemically observed. [Results] Immunohistochemical staining revealed that the myelin sheath and the perineurium in all groups were laminin positive. In the C and E groups, all rats showed normal staining. In contrast, 4 rats in the I group exhibited weak labeling. [Conclusion] Our results suggest that immobilization alters the perineurium at a molecular level and the range of motion exercise is essential for maintaining the environment of the perineurium. PMID- 27190438 TI - Effects of sittercise on elderly subjects' depression and sleep quality. AB - [Purpose] This study examined the effects of sittercise on elderly subjects' depression and sleep quality. [Subjects] The subjects of this quasi-experimental study were divided into an experimental group and a control group. [Methods] The subjects of the experimental group performed sittercise and the control group received no intervention. [Results] The results demonstrate that the subjects who performed sittercise had significantly decreased depression levels compared to the control. They also reported significantly improved sleep quality. [Conclusion] A favorable change in depression levels was seen after sittercise which alse had a significant effect on sleep quality. PMID- 27190439 TI - The combined effects of transcutaneous electrical nerve stimulation (TENS) and stretching on muscle hardness and pressure pain threshold. AB - [Purpose] This study aimed to clarify the immediate effects of a combined transcutaneous electrical nerve stimulation and stretching protocol. [Subjects] Fifteen healthy young males volunteered to participate in this study. The inclusion criterion was a straight leg raising range of motion of less than 70 degrees. [Methods] Subjects performed two protocols: 1) stretching (S group) of the medial hamstrings, and 2) tanscutaneous electrical nerve stimulation (100 Hz) with stretching (TS group). The TS group included a 20-minute electrical stimulation period followed by 10 minutes of stretching. The S group performed 10 minutes of stretching. Muscle hardness, pressure pain threshold, and straight leg raising range of motion were analyzed to evaluate the effects. The data were collected before transcutaneous electrical nerve stimulation (T1), before stretching (T2), immediately after stretching (T3), and 10 minutes after stretching (T4). [Results] Combined transcutaneous electrical nerve stimulation and stretching had significantly beneficial effects on muscle hardness, pressure pain threshold, and straight leg raising range of motion at T2, T3, and T4 compared with T1. [Conclusion] These results support the belief that transcutaneous electrical nerve stimulation combined with stretching is effective in reducing pain and decreasing muscle hardness, thus increasing range of motion. PMID- 27190440 TI - Which is better in the rehabilitation of stroke patients, core stability exercises or conventional exercises? AB - [Purpose] The aim of this study was to determine which is better in the rehabilitation of stroke patients, core stability exercises or conventional exercises. [Subjects and Methods] Forty participants with hemiplegia were recruited in the Department of Neurology of Yidu Central Hospital of Weifang between January 2014 and February 2015 and randomly divided into either an experimental or control group. The patients in the control group performed conventional exercises for six weeks, and those in the experiment group performed core stability exercises for six weeks. The outcomes were evaluated using Modified Barthel Index and Berg Balance Scale. [Results] After treatment, the Modified Barthel Index and Berg Balance Scale were significantly increased in both groups when compared with the baseline. The Modified Barthel Index was significantly lower in the control group compared with the experimental group. The Berg Balance Scale scores in the control group were relatively lower than those in the experimental group, but there was no significant difference between the two groups. [Conclusion] Core stability exercises have a better effect on patients with hemiplegia than conventional exercises. PMID- 27190442 TI - The perceptions and readiness toward interprofessional education among female undergraduate health-care students at King Saud University. AB - [Purpose] Interprofessional education (IPE) is an important academic approach for preparing health-care professionals to provide patient care in a collaborative team environment. This study aimed to measure the perceptions and readiness toward IPE among female undergraduate health-care students at King Saud University (KSU). [Subjects and Methods] A cross-sectional study carried out using a survey in the form of an electronic questionnaire: The Readiness for Interprofessional Learning Scale (RIPLS). The questionnaire was distributed to the students via e-mail and social media networks. [Results] The RIPLS was completed by 296 female health-care students at KSU who valued the importance of IPE. The differences between health-care disciplines in the perceptions and readiness toward IPE were statistically significant, but there were no differences between students of different years of study in their perception and readiness toward IPE. [Conclusion] Administering a course of interprofessional teamwork in the health-care curriculum is a major challenge for the clinical education community. IPE offers an opportunity to address the multi-disciplinary concept in hospitals. Our findings indicate that undergraduate health-care students have high perception and readiness toward IPE. PMID- 27190443 TI - Differences in abdominal muscle activation during coughing between smokers and nonsmokers. AB - [Purpose] The purpose of this study was to compare the activity of the abdominal muscles during coughing between smokers and nonsmokers. [Subjects] A total of 30 healthy adults (15 smokers, 15 nonsmokers) participated. [Methods] The percentage maximal voluntary isometric contraction values (%MVIC) of the rectus abdominis (RA), external abdominal oblique (EO), and internal abdominal oblique (IO) and transversus abdominis (TrA) were measured using surface electromyography. [Results] The %MVIC of the IO and TrA statistically significantly differed and the %MVIC of IO and TrA was found to be higher during coughing in nonsmokers compared with during coughing in smokers. [Conclusion] The activity of the deep abdominal muscles in nonsmokers was also higher than that of smokers during coughing. PMID- 27190441 TI - A study of the effect of visual depth information on upper limb movement by use of measurement of smoothness. AB - [Purpose] This study verified that the smoothness of reaching movements is able to quantitatively evaluate the effects of two- and three-dimensional images on movement in healthy people. In addition, clinical data of cerebrovascular accident patients were also analyzed by the same method. [Subjects] Ten healthy adult volunteers and two male patients with previous cerebrovascular accidents participated. [Methods] The subjects were tasked with reaching for objects shown on a display. The target and virtual limb, rendered with computer graphics, were shown on the display. Movements of the virtual limb were synchronized with those of the subject. Healthy subjects reached for targets with their dominant arm, and cerebrovascular accident patients used their paretic arm. A polarized display and polarized glasses were used when the subjects were shown three-dimensional images. In the present study, jerk cost was used to quantify the smoothness of movement. [Results] Six of the 10 healthy subjects had significantly smoother reaching movements when viewing the three-dimensional images. The two cerebrovascular accident patients tended to have smoother movements in response to the three-dimensional images. [Conclusion] Analysis of the smoothness of movement was able to detect the influence of the depth cue in vision on movement quantitatively for the healthy subjects and cerebrovascular accident patients. PMID- 27190445 TI - Reliability of lower leg proximal end and forefoot kinematics during different paces of barefoot racewalking on a treadmill using a motion recorder (MVP-RF8 BC). AB - [Purpose] This study was performed to investigate the changes in lower leg proximal end and forefoot kinematics, and reliability of measurement during different paces of barefoot racewalking on treadmill. [Subjects] Eleven junior racewalking men participated in this study. [Methods] To identify changes in lower leg proximal end and forefoot kinematics, during different paces of barefoot racewalking on a treadmill, a wireless motion recorder (MVP-RF8-BC) was used. Interclass correlation coefficients (ICC 1, 2) were used to estimate reliability. [Results] There were significant differences in the lower leg proximal end and forefoot maximum medial/lateral rotations at a pace of 9 km/h compared with those at a pace of 5 km/h pace. The intra-examiner reliability estimates ranged from 0.82 and 0.89 to 0.87 and 0.93 for lower leg proximal end inversion/eversion rotation and medial/lateral rotation, and from 0.92 and 0.84 to 0.93 and 0.91 for forefoot inversion/eversion rotation and medial/lateral rotation. [Conclusion] We conclude that the lower leg proximal end and forefoot kinematics of barefoot racewalking on a treadmill are influenced by different paces and that assessment of lower leg proximal end and forefoot kinematics by means of the wireless motion recorder (MVP-RF8-BC) is adequately reliable. This information may be useful for determining exercise prescriptions. PMID- 27190444 TI - Comparisons of knee and ankle joint angles and ground reaction force according to functional differences during single-leg drop landing. AB - [Purpose] The purpose of this study was to determine potential predictors of functional instability of the knee and ankle joints during single-leg drop landing based on the prior history of injury. [Subjects and Methods] The subjects were 24 collegiate soccer players without pain or dysfunction. To compare the differences between the stable and unstable sides during single-leg drop landing, 8 motion analysis cameras and a force plate were used. The Cortex 4 software was used for a biomechanical analysis of 3 events. An independent t-test was used for statistical comparison between both sides; p<0.05 indicated significance. [Results] The knee joint movements showed gradual flexion in the sagittal plane. The unstable-side ankle joint showed plantar flexion of approximately 2 degrees relative to the stable side. In the coronal plane, the unstable-side knee joint differed from the stable side in its tendency for valgus movement. The unstable side ankle joint showed contrasting movement compared with the stable side, and the difference was significant. Regarding the vertical ground reaction force, the stable side showed maximum knee flexion that was approximately 0.1 BW lower than that of the unstable side. [Conclusion] Increasing the flexion angle of the knee joint can help prevent injury during landing. PMID- 27190446 TI - Effects of Kinesio taping on joint position sense of the ankle. AB - [Purpose] The purpose of this study was to examine the effect of Kinesio taping on the joint position sense of the ankle. [Subjects and Methods] The subjects of this study were 26 nomal adults who had experienced ankle sprain. Kinesio taping was applied over the ankle medial ligament and ankle lateral ligament with eight pattern reinforcement taping. Joint position sense was measured using isokinetic equipment (Biodex System 4 pro dynamometer, Biodex Medical systems Inc., USA) during dorsiflexion/plantarflexion and inversion/eversion, before and after taping. Statistical analyses were performed using SPSS 21.0 for Windows. [Results] Joint position sense after Kinesio taping was improved in the dorsiflexion and inversion positions. [Conclusion] According to the results of this study, Kinesio taping of the ankle is effective for the prevention of ankle sprain. PMID- 27190447 TI - Handgrip strength deficits best explain limitations in performing bimanual activities after stroke. AB - [Purpose] To evaluate the relationships between residual strength deficits (RSD) of the upper limb muscles and the performance in bimanual activities and to determine which muscular group would best explain the performance in bimanual activities of chronic stroke individuals. [Subjects and Methods] Strength measures of handgrip, wrist extensor, elbow flexor/extensor, and shoulder flexor muscles of 107 subjects were obtained and expressed as RSD. The performance in bimanual activities was assessed by the ABILHAND questionnaire. [Results] The correlations between the RSD of handgrip and wrist extensor muscles with the ABILHAND scores were negative and moderate, whereas those with the elbow flexor/extensor and shoulder flexor muscles were negative and low. Regression analysis showed that the RSD of handgrip and wrist extensor muscles explained 38% of the variance in the ABILHAND scores. Handgrip RSD alone explained 33% of the variance. [Conclusion] The RSD of the upper limb muscles were negatively associated with the performance in bimanual activities and the RSD of handgrip muscles were the most relevant variable. It is possible that stroke subjects would benefit from interventions aiming at improving handgrip strength, when the goal is to increase the performance in bimanual activities. PMID- 27190448 TI - Effects of Kinesio taping and Mcconnell taping on balance and walking speed of hemiplegia patients. AB - [Purpose] The aim of this study was to evaluate the overlap effect of the PNF following the application of Kinesio taping and the McConnell taping, and also the impact of the taping application method on the balance and walking speed of the patients with stroke. [Subjects and Methods] Thirty-six patients who were diagnosed with hemiplegia due to stroke were selected as subjects of this study. They were randomly and evenly divided into experiment group 1 (Kinesio taping group), experiment group 2 (McConnell taping group), and the control group; each group had 12 patients. [Results] The Berg balance scale (BBS) was used to evaluate balance, and the ability in this study. A 10 m walking test (10MWT) was performed to measure the walking speed. Experiment group 1 showed a statistically significant improvement in balance and walking speed compared to experiment group 2, and the control group in week 4 and week 8. [Conclusion] Application of Kinesio taping had a more beneficial effect on the balance and walking speed than joint-fixation taping of the patients with stroke. PMID- 27190449 TI - Walking gait changes after stepping-in-place training using a foot lifting device in chronic stroke patients. AB - [Purpose] The goal of this study was to investigate the efficacy of stepping-in place training using a foot lifting assist device on the walking gait of chronic hemiparetic stroke patients. [Subjects] Seven patients with chronic hemiplegic stroke (age 80.9+/-4.9 years) who were attending a local adult daycare facility participated in this study. [Methods] The participants had 2 or 16 weeks of intervention after a baseline period of 2 weeks. Evaluations were performed before the baseline period and before and after the intervention period. The evaluation consisted of a two-dimensional motion analysis of walking and stepping in-place exercises and a clinical evaluation. [Results] Walking speed increased in three participants after 2 or 16 weeks of intervention. The swing phase percentage increased in the paretic gait cycle, and the time from non-paretic heel contact to paretic heel off decreased during stepping-in-place in these participants. [Conclusion] Given that the transition from the support phase support to the swing phase was shortened after the intervention, the stepping-in place exercise using the device designed for this study may improve the muscle strength of the lower limb and coordination in the pre-swing phase of the paretic limb. PMID- 27190450 TI - Comprehensive geriatric assessment of effects of hospitalization and long-term rehabilitation of patients following lower extremity arthroplasty. AB - [Purpose] This study was performed to examine the effects of subacute physical therapy (PT) on activities of daily living (ADL), quality of life, and geriatric aspects of patients who underwent total knee arthroplasty (TKA) or total hip arthroplasty (THA). [Subjects] The subjects were TKA (n=56) and THA (n=39) patients who received PT on the first day of independent ADL (up to 2 weeks) and just prior to discharge (4 weeks). [Methods] The functional independence measure (FIM), grip strength, knee extension strength (KES), timed up and go (TUG) test, mini-mental state examination (MMSE), geriatric depression scale short form (GDS 15), fall efficacy scale (FES), and medical outcome study 8-item short-form health survey (SF-8) were used as outcome measure, and comorbidity involvement was also investigated. [Results] Improvements in FIM, KES, TUG, GDS-15, FES, and SF-8 scores were seen in both groups (effect size, 0.31-0.87). Poor PT effects were found for THA patients aged >=65 years, for TKA and THA patients with an MMSE score <=28, and for THA patients with two or more comorbidities. [Conclusion] Positive effects were seen in patients who received PT at 2-4 weeks after surgery. Thus, additional PT for approximately 2 weeks after the beginning of independent ADL may be beneficial. PMID- 27190452 TI - Effect of the a circuit training program using obstacles on the walking and balance abilities of stroke patients. AB - [Purpose] The aim of this study was to investigate the impact of a circuit training program on the walking and balance abilities of stroke patients using an up-to-date walking analysis device. [Subjects and Methods] The subjects of this study were 12 adults who were diagnosed with stroke. Evaluation was conducted using the Smart Step test for walking ability; (BBS) for balance ability; and the Timed Up and Go test (TUG) for functional mobility and movement ability. The 12 stroke patients were randomly recruited and divided into two groups; an experimental group which performed circuit training with obstacles, and a control group which performed flat gait training). [Results] Between-group comparison of the change in the 10-m walking speed found a statistically significant difference between the two groups. Between-group comparison of the changes in BBS and TUG found statistically significant differences between the two groups. [Conclusion] The circuit training program using obstacles had a positive effect on the gait and balance abilities of the stroke patients. PMID- 27190451 TI - The effects of biomechanical foot orthoses on the gait patterns of patients with malalignment syndrome as determined by three dimensional gait analysis. AB - [Purpose] The biomechanical effects of foot orthoses on malalignment syndrome have not been fully clarified. This experimental investigation was conducted to evaluate the effects of orthoses on the gait patterns of patients with malalignment syndrome. [Subjects and Methods] Ten patients with malalignment syndrome were recruited. For each participant, kinematic and kinetic data were collected under three test conditions: walking barefoot, walking with flat insoles in shoes, and walking with a biomechanical foot orthosis (BFO) in shoes. Gait patterns were analyzed using a motion analysis system. [Results] Spatiotemporal data showed the step and stride lengths when wearing shoes with flat insoles or BFO were significantly greater than when barefoot, and that the walking speed when wearing shoes with BFO was significantly faster than when walking barefoot or with shoes with flat insoles. Kinetic data, showed peak pelvic tilt and obliquity angle were significantly greater when wearing BFO in shoes than when barefoot, and that peak hip flexion/extension angle and peak knee flexion/extension and rotation angles were significantly greater when wearing BFO and flat insoles in shoes than when barefoot. [Conclusion] BFOs can correct pelvic asymmetry while walking. PMID- 27190453 TI - Impact of pregnancy on back pain and body posture in women. AB - [Purpose] The purpose of this single-center investigation was to study the impact of pregnancy on back pain and body posture. [Subjects] The subjects were 26 pregnant females. [Methods] Data were generated with a spine scanner (Diers((r)) formetric 4D), trunk strength measurement (Diers((r)) myoline), a numeric pain scale (0 to 10), and a biomechanical model. Parameters were compared during each trimester. [Results] The alteration in pain level at rest and lumbar lordosis angle in the females revealed a statistical trend during pregnancy. Spearman's test showed positive correlations between body weight and trunk inclination during the second trimester, and between body weight and the kyphosis angle in the third trimester. The trunk inclination and the kyphosis angle revealed a negative correlation in the third trimester. Based on our analysis, the highest moments and muscle strength must be expended in the third trimester. The actual muscle strength is greatest in the second trimester. [Conclusion] Pain at rest must be given greater attention in pregnant females, and their increasing lumbar kyphosis must be counteracted. Exercising the deep segmental muscles may serve as a preventive measure. PMID- 27190454 TI - Relationships between self-reported and performance-based measures of functional capacity in individuals with chronic stroke. AB - [Purpose] The aim of this study was to investigate the associations between self reported and valid performance-based measures of functional capacity in individuals with chronic stroke. [Subjects and Methods] Self-reported measures of functional capacity of 31 individuals with chronic stroke were assessed by the Duke Activity Status Index scores, whereas performance-based measures were assessed by the distance covered (in meters) and oxygen consumption (relative oxygen consumption, in ml.kg(-1).min(-1) ) during the six-minute walking test. [Results] The subjects had a mean age of 58.6+/-13 years and a mean time since the onset of stroke of 28.3+/-15.1 months. They had a mean Duke Activity Status Index of 27.3+/-14.4, mean distance covered of 325.2+/-140.2 m, and mean relative oxygen consumption of 9.6+/-2.3 ml.kg(-1).min(-1) . Significant, positive, and moderate to good correlation coefficients were found between the Duke Activity Status Index scores and the distance covered during the six-minute walking test (r=0.68). Significant, positive, and fair associations were also found between the Duke Activity Status Index scores and relative oxygen consumption values obtained during the six-minute walking test (r=0.45). [Conclusion] The findings of the present study support the clinical use of the Duke Activity Status Index as a tool to assist in clinical evaluations of functional capacity of individuals with chronic stroke. PMID- 27190455 TI - Effects of Nordic walking on pelvis motion and muscle activities around the hip joints of adults with hip osteoarthritis. AB - [Purpose] Increased compensatory pelvic movement is remarkable in limping patients with hip osteoarthritis (OA). However, a method of improving limping has not been established. The purpose of this study was to identify the effects of two types of Nordic walking by analyzing the pelvic movement and muscle activities of adults with hip OA. [Subjects and Methods] Ten patients with OA of the hip performed Japanese-style Nordic walking (JS NW), European-style Nordic walking (ES NW), and Ordinary walking (OW), and the muscle activities around the hip joint and pelvic movements were analyzed. [Results] The pelvic rotation angle was significantly larger in ES NW than in JS NW. In the stance phase, hip abductor muscle activity was significantly decreased in JS NW compared to both OW and ES NW. In the swing phase, rectus abdominis muscle activity was significantly increased in both JS NW and ES NW compared to OW and lumbar erector spinae activity was significantly lower in JS NW than in OW. [Conclusion] JS NW style may reduce the compensatory pelvic rotation in patients with hip OA. JS NW might be better for joint protection and prevention of secondary disorders of the hip in OA patients. PMID- 27190456 TI - Acute effect of scapular proprioceptive neuromuscular facilitation (PNF) techniques and classic exercises in adhesive capsulitis: a randomized controlled trial. AB - [Purpose] The aim of our study was to compare the initial effects of scapular proprioceptive neuromuscular facilitation techniques and classic exercise interventions with physiotherapy modalities on pain, scapular dyskinesis, range of motion, and function in adhesive capsulitis. [Subjects and Methods] Fifty three subjects were allocated to 3 groups: scapular proprioceptive neuromuscular facilitation exercies and physiotherapy modalities, classic exercise and physiotherapy modalities, and only physiotherapy modalities. The intervention was applied in a single session. The Visual Analog Scale, Lateral Scapular Slide Test, range of motion and Simple Shoulder Test were evaluated before and just after the one-hour intervention in the same session (all in one session). [Results] All of the groups showed significant differences in shoulder flexion and abduction range of motion and Simple Shoulder Test scores. There were statistically significant differences in Visual Analog Scale scores in the proprioceptive neuromuscular facilitation and control groups, and no treatment method had significant effect on the Lateral Scapular Slide Test results. There were no statistically significant differences between the groups before and after the intervention. [Conclusion] Proprioceptive neuromuscular facilitation, classic exercise, and physiotherapy modalities had immediate effects on adhesive capsulitis in our study. However, there was no additional benefit of exercises in one session over physiotherapy modalities. Also, an effective treatment regimen for shoulder rehabilitation of adhesive capsulitis patients should include scapular exercises. PMID- 27190458 TI - Fatigue and pain related to internet usage among university students. AB - [Purpose] This study was performed to assess fatigue and pain levels related to internet usage among university students. The dominant regions of fatigue and pain in the body were examined, as well as differences in fatigue and pain levels among students. [Subjects and Methods] The study used a descriptive survey and a convenience sample of 378 students from a single university. The data were collected from January 1 to June 31, 2015. Fatigue and pain levels were measured using a visual analog scale. [Results] The average reported by the participants 4.7 and 3.7 levels of fatigue and pain, respectively. The regions with the highest fatigue scores were the eyes, followed by the neck, and shoulders. The regions with the highest pain scores were the neck, followed by the shoulders, and the waist. The results show that participants' fatigue and pain levels depended on the duration of their internet use per day. [Conclusion] These findings indicate that control of internet usage time is needed to maintain the well-being of university students who use the internet. PMID- 27190459 TI - Analysis of electromyographic activities of the lumbar erector spinae caused by inversion traction. AB - [Purpose] The purpose of this study was to analyze changes in the electromyographic activities of the lumbar erector spinae caused by inversion traction in order to verify the relaxation effect. [Subjects and Methods] The subjects included 60 healthy male adults who were equally and randomly assigned to a 30-30 degrees group, a 30-60 degrees group, and a 60-60 degrees group. Inversion traction was performed for six minutes, and the electromyographic activities of the lumbar erector spinae (L2, L4) were measured before and after inversion traction. [Results] The root mean square values at the L2 and L4 levels on both sides were statistically significantly higher after inversion traction compared with before inversion traction. Before inversion traction, the root mean square values at the L2 and L4 levels on both sides in the 30-60 degrees group and 60-60 degrees group were significantly higher than those in the 30-30 degrees group, while the root mean square values at the L2 and L4 levels on both sides showed no significant differences between the groups before inversion traction. [Conclusion] The findings of this study indicated that IT is more likely to elicits an increase in muscle tension and prevent relaxation of the lumbar erector spinae. PMID- 27190457 TI - Factors affecting the discharge destination of hip fracture patients who live alone and have been admitted to an inpatient rehabilitation unit. AB - [Purpose] (1) The aim of this study was to examine relations between clinical and functional assessment and discharge destination and (2) to identify the optimal cutoff point for estimating discharge to home after inpatient rehabilitation. [Subjects] The subjects were 54 hip fracture patients (15 males, 39 females; mean age 81.3 +/- 7.4 years) living alone. [Methods] The patients were classified into two groups: those discharged to home and those admitted to an institution. Age, gender, side of fracture, fracture type, number of comorbidities, Functional Independence Measure motor score, and Functional Independence Measure cognitive score were compared between groups. Multiple logistic regression analysis was conducted with discharge to home as the dependent variable and age, gender, side of fracture, fracture type, number of comorbidities, Functional Independence Measure motor score, and Functional Independence Measure cognitive score as independent variables. A receiver operating characteristic curve analysis was used to identify a cutoff point for classification of the patients into the two groups. [Results] Multiple logistic regression analysis showed that the Functional Independence Measure cognitive score was a significant variable affecting the discharge destination. The receiver operating characteristic curve analysis revealed that discharge to home was predicted accurately by a Functional Independence Measure cognitive score of 23.5. [Conclusion] Information from this study is expected to be useful for determining discharge plans and for the setting of treatment goals. PMID- 27190460 TI - Effects of insoles contact on static balance. AB - [Purpose] This study examined the effect of the degree of the contact area between the insoles and soles on static balance. [Subjects and Methods] Thirteen healthy male and female adults voluntarily participated. All of the subjects wore three different types of insoles (no orthotic insole, partial contact, full contact) in the present experiment. The subjects were instructed to place both feet parallel to each other and maintain static balance for 30 seconds. Center of pressure parameters (range, total distance, and mean velocity) were analyzed. [Results] The results show that the anteroposterior range and mediolateral (ML) total distance and velocity decreased when orthotic insoles with partial contact or full contact were used in comparison to when a flat insole (no orthotic insole) was used. Also, the ML range and total distance were lower with full contact than in the other two conditions. These results indicate that static balance improves as the degree of contact between the soles and insoles increases. [Conclusion] The results of this study suggests that using insoles with increased sole contact area would improve static balance ability. PMID- 27190461 TI - The effect of hip joint muscle exercise on muscle strength and balance in the knee joint after meniscal injury. AB - [Purpose] This study aimed to evaluate the effect of hip muscle strengthening on muscle strength and balance in the knee joint after a meniscal injury. [Subjects and Methods] This randomized control study enrolled 24 patients who had undergone arthroscopic treatment after a meniscal injury and began a rehabilitative exercise program 8 weeks after surgery. Subjects were divided into 2 groups of 12 subjects each: gluteus medius resistance exercise group and control group. This study investigated muscle strength and balance in the knee joint flexor, extensor, and abductor during an 8-week period. [Results] Measurements of knee extensor muscle strength revealed no significant difference between the control group and the experimental group. Measurements of abductor muscle strength, however, identified a significant difference between the 2 groups. The groups did not differ significantly with regard to balance measurements. [Conclusion] The results of this study suggest that this subject should be approached in light of the correlation between the hip abductor and injury to the lower extremities. PMID- 27190463 TI - Age-related differences in control of a visuomotor coordination task: a preliminary study. AB - [Purpose] The purpose of the current study was to examine age-related differences in control of a perception-action coordination skill. We adapted a visuomotor tracking experiment requiring various coordination patterns between a limb's motion and an external signal. [Subjects and Methods] A total of 12 subjects (6 elderly and 6 young) voluntarily participated in the study. The experimental session consisted of 3 trials for 3 different relative phase patterns: 0 degrees , 90 degrees , and 180 degrees , defined by the relationship between the online visual feedback of the joystick motion and the white dot signal. [Results] The 0 degrees and 180 degrees tracking patterns were stable compared with the 90 degrees tracking pattern for both age groups. The present results also showed that the elderly subjects were less stable than were young subjects for all tracking patterns. [Conclusion] The intrinsic coordination dynamics predicted by the Haken-Kelso-Bunz (HKB) mathematical model did not change with age, whereas utilization of visual feedback information declined overall. Further research is needed regarding methods for increasing utilization of visual feedback information from the perspective of rehabilitation. PMID- 27190462 TI - Association between nutritional status and Modic classification in degenerative disc disease. AB - [Purpose] This study was conducted to examine the association between Modic classification and the eating habits in patients with degenerative disc disease (DDD) and to determine the influence of nutrition on disease severity. [Subjects and Methods] Sixty patients with DDD visiting a low back pain outpatient clinic were enrolled. Through face-to-face interviews, they completed questionnaires regarding their demographics, disease activity, smoking and alcohol use, concomitant diseases, disease duration, and nutritional status.Exclusion criteria were age <20 years or >65 years, other comorbidities, missing MRI data, and inability to speak Turkish. [Results] Forty patients were finally included in the study. The frequency with which they consumed water, salt, fast food, eggs, milk, yogurt, cheese, whole wheat bread, white bread, butter, and margarine was recorded. A weak negative correlation was observed between the Modic types and fish and egg consumption. [Conclusion] Modic changes, which indicate the severity of DDD, seem to be correlated to patients' dietary habits. However, studies with comparison groups and larger samples are needed to confirm our promising results before any cause-and-effect relationship can be proposed. PMID- 27190464 TI - Effects of treadmill exercise on skeletal muscle mTOR signaling pathway in high fat diet-induced obese mice. AB - [Purpose] The aim of this study was to investigate the effects of regular treadmill exercise on skeletal muscle Rictor-Akt and mTOR-Raptor-S6K1 signaling pathway in high-fat diet-induced obese mice. [Subjects and Methods] Four- week old C57BL/6 mice were adopted and classified into normal diet group (ND, n = 10), normal diet and training group (NDT, n = 10), high-fat diet group (HF, n = 10), and high-fat diet and training group (HFT, n = 10). The exercise program consisted of a treadmill exercise provided at low intensity for 1-4 weeks, and moderate intensity for 5-8 weeks. [Results] The Western blot method was used to measure the expression of mTOR, Raptor, S6K1, Rictor, and Akt proteins in the soleus muscle. mTOR levels were significantly higher in the HF group than in the ND and NDT groups. Raptor/mTORC1 and S6K1 levels were significantly higher in the HF group than in all the other groups. Akt levels were significantly lower in the HF group than in the NDT group. The risk of obesity may be associated with the overactivation of the mTOR-Raptor-S6K1 signaling pathway and a decrease in Akt levels. [Conclusion] This study also indicates that performing aerobic exercise may be associated with the downregulation of the mTOR-Raptor-S6K1 pathway. PMID- 27190465 TI - Thera-band((r)) elastic band tension: reference values for physical activity. AB - [Purpose] The aim of this technical note was to report significant differences in the tension forces of the different-sized Thera-band((r)) elastic bands (Hygenic Corp.) determined by us versus the manufacturer. [Subjects] Two trained observers performed all measurements. [Methods] The tension force (kilogram-force units) of eight color-coded elastic bands (tan, yellow, red, green, blue, black, silver, and gold) with different resistance levels was measured at 10 different percentages of elongation (25% to 250% with 25% increments) using an electronic elongation gauge tensiometer. [Results] There were significant differences in the tension force of the elastic bands of different colors when compared in pairs (excepting the tan/yellow pair) at 100% and 200% elongation, as determined via one-way analysis of variance. There were no differences in the slopes for the tan versus yellow and green versus blue bands, as determined via linear regression analysis and one-way analysis of variance. Comparison of the tension force values obtained in our study with the reference values of the manufacturer (the t-test applied to the slopes) showed significant differences for five colors (yellow, green, blue, silver, and gold). [Conclusion] Our results indicate that the tension force values for Thera-Band elastic bands provided by the manufacturer are overestimates. PMID- 27190466 TI - The relation between vitamin D and postural balance according to clinical tests and tetrax posturography. AB - [Purpose] To evaluate the association between Vitamin D and risk of falling, balance, and lower extremity neuromuscular function in women aged 60 and above by using Tetrax posturography. [Subjects and Methods] A total 200 women were classified based on their 25-OH-vitamin D (25(OH)D) values: hypo-vitaminosis group (less than 50.0 nmol/l) and normal group (50.0 more). Balance was measured using a Tetrax((r)) posturography device (Sunlight Medical Ltd, Israel). Falling risk, stability index (SI), and weight distribution index (WDI) were calculated. Short Physical Performance Battery (SPPB) and International Physical Activity Questionnaire (IPAQ) were used as the clinical tests. [Results] Standing balance, gait, chair stand performance and total SPPB scores were significantly better in the patients with serum 25(OH)D levels higher than 50.0 nmol/l. Similarly, falling risk and SI values in the most of the postures were significantly higher in the hypovitaminosis group. There were significant associations between serum 25(OH)D levels with SPPB total score and Tetrax-measured falling risk. [Conclusion] This study showed better balance control, lower extremity function, and reduced falling risk in patients with serum 25(OH)D levels higher than 50.0 nmol/l in women aged 60 and above. PMID- 27190467 TI - Effects of deep heating provided by therapeutic ultrasound on demyelinating nerves. AB - [Purpose] Physiotherapeutic heating agents are classified into two groups: superficial-heating agents and deep-heating agents. Therapeutic ultrasound is a deep-heating agent used to treat various musculosketal disorders. Numerous studies have attempted to determine the impact of ultrasound on healthy nerve conduction parameters. However, the instantaneous effects of deep heating via ultrasound on demyelinating nerves do not appear to have been described previously. The present study aimed to assess and compare the impact of ultrasound on demyelinating nerve and healthy nerve conduction parameters. [Subjects and Methods] Carpal tunnel syndrome was used as a focal demyelination model. Thirty-two hands of 25 participants with carpal tunnel syndrome were enrolled in the study. Ultrasound parameters were 3.3 MHz, 1.0 W/cm(2), 8 minutes, and continuous wave. Electrodiagnostic studies were performed initially, at the midpoint (4th min), and immediately after (8th min) ultrasound application. [Results] Reduced motor conduction velocity was found in demyelinating nerves at the 4th and 8th minutes. Ulnar nerve onset latency was significantly prolonged in the 8th minute recording, compared to the initial value. There were no significant differences in relative velocity and latency changes between demyelinating and normal nerves. [Conclusion] Deep heating via ultrasound may inversely affect conduction velocity in demyelinating nerves. PMID- 27190468 TI - Effects of pelvic adjustment on pelvic posture and angles of the lower limb joints during walking in female university students. AB - [Purpose] This study investigated the effects of pelvic adjustment on pelvic posture and lower limb joint angles during walking in female university students. [Subjects] Thirty healthy female university students were randomly assigned to an experimental group (pelvic adjustment group, n = 15) and a control group (stretching group, n = 15). [Methods] Pelvic adjustment was performed three times on the experimental group. The control group performed three sets of pelvic muscle stretching for 15 minutes. A back mapper and motion analysis equipment were used to measure pelvic posture and angles of lower limb joints for the experimental and control group. [Results] The values obtained before and after the intervention were compared. For the experimental group, the results were significantly different in terms of reduced differences in hip flexion between the left and right hips and in knee abduction between the left and right knees. Differences in pelvic position and pelvic torsion were also found in the experimental group. No significant differences in the control group were identified. [Conclusion] Pelvic adjustment affects pelvic position and torsion and this enhancement to pelvic stability decreases hip flexion and knee abduction during walking. PMID- 27190470 TI - The effect of peculiar complex core balance training on isokinetic muscle functions of the knee and lumbus. AB - [Purpose] This study aimed to investigate the effect of peculiar complex core balance training on the isokinetic muscle function of the knee joint and lumbus to provide fundamental data for establishing a training program that focuses on improving the performance and prevention of injury by developing the core and low extremity muscles. [Subjects and Methods] The participants in this study included a total of ten high school athletes involved in a throwing event for over five years. The subjects were randomly divided into two groups: The experimental group (N=5) and the control group (N=5). The experimental group underwent peculiar complex core balance training. [Results] According to the analysis of covariance, there was a significant effect of peculiar complex core balance training. Therefore, the isokinetic muscle function of the knee joint and lumbus in the experimental group participating in peculiar complex core balance training was significantly increased compared to the control group. [Conclusion] It is concluded that peculiar complex core balance training had a positive effect on the isokinetic muscle function of the knee and lumbus in throwing event athletes. PMID- 27190469 TI - Effects of muscle strength asymmetry between left and right on isokinetic strength of the knee and ankle joints depending on athletic performance level. AB - [Purpose] The aim of this study was to collect basic data on the effect of asymmetry on the muscle strength of the left and right knee and ankle joints of soccer players at varying athletic performance levels, to guide the development of improved exercise programs. [Subjects and Methods] Forty-nine soccer players at three athletic performance levels participated: 15 professional, 16 amateur, and 18 college. Knee extensor and flexor strength were measured at 60 degrees /sec and 180 degrees /sec, and ankle plantar flexor and dorsiflexor strength were measured at 30 degrees /sec and at 120 degrees /sec. Variables were analyzed by one-way ANOVA. [Results] College soccer players showed greater muscle strength at 60 degrees /sec and 180 degrees /sec in the knee extension muscles of both the right and the left sides, lower muscle strength at 30 degrees /sec and 120 degrees /sec in the dorsiflexor of the right ankle, and similar levels of asymmetry between left and right. The maximum muscle strength on the same side significantly differed in the right ankle joint, with asymmetry between left and right at 30 degrees /sec and 120 degrees /sec. [Conclusion] These findings suggest that muscle strength asymmetry in the ankle joint may lead to counterbalancing muscle strengthening of the knee joint to maintain the center of body mass. PMID- 27190472 TI - Elastic therapeutic tape: do they have the same material properties? AB - [Purpose] Elastic therapeutic tape has been widely used for rehabilitation and treatment of sports injuries. Tapes with different elastic properties serve different treatment purposes with inappropriate tension reducing tape effectiveness. Many tapes are available in the market, but studies on tape properties are limited. The aim of this study was to examine the material properties of elastic therapeutic tape. [Subjects and Methods] Brands of elastic therapeutic tape included KinesioTex((r)), ATex, Mueller, 3M, and ThaiTape. The Material Testing System Insight((r)) 1 Electromechanical Testing Systems was used to apply a tensile force on elastic therapeutic tape. Ten specimens of each brand were tested. Stress, load, and Young's modulus at 25%, 50%, 75%, 100%, and maximum point were collected. One-way analysis of variance with post hoc testing was used to analyze tape parameters. [Results] Maximum elongation and Young's modulus at all percentages were significantly different between brands. There were no differences in maximum load and maximum stress. [Conclusion] Mechanical properties are different for commercial elastic therapeutic tapes. Physiotherapists and other clinicians should be aware of mechanical tape properties to correctly apply kinesio tape. PMID- 27190471 TI - The effect of flexi-bar exercise with vibration on trunk muscle thickness and balance in university students in their twenties. AB - [Purpose] The purpose of this research was to determine the effect of Flexi-Bar exercise with vibration on trunk muscle thickness and balance in university students in their twenties. [Subjects and Methods] This research evaluated 26 university students in their twenties, equally and randomly divided into two groups. Both the experimental and control groups used an ordinary pole for exercise. In addition, the experimental group exercised by using a Flexi-Bar. Ultrasonic imaging was used to measure the changes in trunk muscle thickness. A balance measuring equipment was used to measure balance ability. [Results] The thickness of the transversus abdominis and the multifidus muscles in the experimental group increased, and the experimental group showed increased thickness in the transversus abdominis muscle compared to the control group. After 6 months of exercise, there was an improvement in the blind Romberg test and center of pressure moving distance with one-leg standing. [Conclusion] These results indicate that the Flexi-Bar exercise is effective in increasing trunk muscle thickness and improving balance. PMID- 27190473 TI - Improvement of tactile roughness discrimination acuity correlates with perception of improved hand function in patients after hand surgery. AB - [Purpose] The purpose of this study was to elucidate how well patients' perceptions related to the improvements in their hand function during hospitalization. [Subjects] Sixteen patients who were hospitalized after hand surgery. [Methods] Using the Japanese Society for Surgery of the Hand edition of the Quick-Disabilities of the Arm, Shoulder, and Hand questionnaire; tactile roughness discrimination acuity, motor imagery, motor function, sensory function, and pain of the upper limb were assessed at admission and discharge. Spearman's rank-order correlation coefficients were calculated using the differences in all assessment items at admission and discharge. A multiple regression analysis (stepwise method) was performed to investigate factors that correlated with improvements in Quick-Disabilities of the Arm, Shoulder, and Hand scores. [Results] The improvement of tactile roughness discrimination acuity was significantly associated with patient perception of improved hand function. [Conclusion] The results suggest that an improvement in tactile roughness discrimination acuity was most strongly correlated with patient perception of improved hand function. PMID- 27190474 TI - The relationship between health-related quality of life and higher-level functional capacity in elderly women with mild cognitive impairment. AB - [Purpose] To clarify health-related quality of life (HR-QOL) in subjects with mild cognitive impairment (MCI), using EuroQOL (EQ-5D), and to investigate the relationship between HR-QOL and Tokyo Metropolitan Institute Gerontology Index of Competence (TMIG-IC) scores. [Subjects and Methods] The subjects included 25 women with MCI or frail constitutions. A variety of methods were used to assess mental states and activities of daily living (ADL). [Results] EQ-5D scores were significantly lower in the MCI group than in the normal cognitive (NC) group. Among the assessed subscales, the percentages of participants with "moderate problems" during self-care and "moderate and extreme problems" during usual activities were significantly higher in the MCI group. TMIG-IC scores were significantly lower in the MCI group than in the NC group. There was a positive correlation between TMIG-IC and EQ-5D scores in the MCI group. There were also significant positive correlations between instrumental activities of daily living and social roles between EQ-5D and TMIG-IC scores in the MCI group. [Conclusion] TMIG-IC scores may reflect cognitive disorders earlier than BI and FIM. The decline of TMIG-IC scores, especially for IADL and social roles, affects HR-QOL even in the early phases of cognitive impairment. PMID- 27190475 TI - A quantitative assessment of the mechanical effects on the lumbar spine and the effects on straight leg raising and lumbar flexion of segmental sustained rotation. AB - [Purpose] This study were to examine the strength and relative direction of the applied force from lumbar segmental sustained rotation (LSSR) on the lumbar spinous process, and to clarify the effects of LSSR on straight leg raising (SLR) and lumbar flexion (LF). [Subjects] 18 pain-free healthy adults volunteered for this study. [Methods] Applied force and direction were measured between the L5-S1 segments using tri-axial pressure sensors. Subjects participated in 3 trials. Subjects underwent localized right rotation, held for 10 seconds, of the L5 in relation to the S1. Sham group subjects followed LSSR group protocols; however L5 S1 rotation was absent. Control subjects rested on a plinth. SLR and LF were measured pre and post-trial. [Results] Outcome data for LSSR forces were as follows; x (0.06N (+/-0.29)), y (-5.26N (+/-0.01)), z (6.16N (+/-1.33)), and resultant vector magnitude (8.19N (+/-1.12)). LSSR relative direction results were as follows: x-axis angle, 89. 6 degrees (+/-1.5); y-axis, 130.9 degrees (+/-5.6); and z-axis, 41.6 degrees (+/-4.7). The LSSR group's LF and SLR were significantly increased compared with those of the sham and control groups. [Conclusion] The identified resultant vector magnitude was 8.19N, less than other techniques. LSSR effectively improves LF and bilateral SLR. PMID- 27190476 TI - Comparison of body composition, heart rate variability, aerobic and anaerobic performance between competitive cyclists and triathletes. AB - [Purpose] The aim of this study was to compare the body composition, heart rate variability, and aerobic and anaerobic performance between competitive cyclists and triathletes. [Subjects] Six cyclists and eight triathletes with experience in competitions voluntarily participated in this study. [Methods] The subjects' body composition was measured with an anthropometric tape and skinfold caliper. Maximal oxygen consumption and maximum heart rate were determined using the incremental treadmill test. Heart rate variability was measured by 7 min electrocardiographic recording. The Wingate test was conducted to determine anaerobic physical performance. [Results] There were significant differences in minimum power and relative minimum power between the triathletes and cyclists. Anthropometric characteristics and heart rate variability responses were similar among the triathletes and cyclists. However, triathletes had higher maximal oxygen consumption and lower resting heart rates. This study demonstrated that athletes in both sports have similar body composition and aerobic performance characteristics. PMID- 27190477 TI - Effects of screen size on smartphone functionality and usability for stroke patients with hemiparalysis. AB - [Purpose] The effect of screen size on smartphone functionality and usability for patients with stroke, considering both the non-dominant and dominant hand smartphone usage, was investigated in this study. [Subjects and Methods] Thirteen patients with stroke participated in this study-five pre-non-dominant hand users and eight pre-dominant hand users. The smartphone screen sizes used were 4.2, 4.5, and 5.6 inches. Usability was assessed in terms of discomfort experienced during dragging operations, which was self-reported using a four-point Likert scale. Functionality was assessed in terms of completion time and the frequency of errors in the task requiring users to quickly touch numbers 0 through 9 in order on the keypad. [Results] For all three screen sizes, a significant difference between the dominant and non-dominant hands was found in usability, completion time, and frequency of errors. For dominant hand users, differences in usability and completion time were found among the three screen sizes. Among the three screen sizes, no difference in the frequency of errors was found in either of the groups. [Conclusion] This study will be useful as basic research on usability and functionality with stroke patients using only pre-non-dominant or pre-dominant hand. PMID- 27190478 TI - Smooth-pursuit eye movements without head movement disrupt the static body balance. AB - [Purpose] To investigate the changes of body balance in static posture in smooth pursuit eye movements (SPEMs) without head movement. [Subjects and Methods] Forty subjects (24 males, 16 females) aged 23.24 +/- 2.58 years participated. SPEMs were activated in three directions (horizontal, vertical, and diagonal movements); the target speed was set at three conditions (10 degrees /s, 20 degrees /s, and 30 degrees /s); and the binocular visual field was limited to 50 degrees . To compare the body balance changes, the general stability (ST) and the fall risk index (FI) were measured with TETRAX. The subjects wore a head-neck collar and stood on a balance plate for 32 s during each measurement in three directions. SPEMs were induced to each subject with nine target speeds and directions. All measured values were compared with those in stationary fixation. [Results] The ST and FI increased significantly in all SPEMs directions, with an increased target speed than that in stationary fixation. In the same condition of the target speed, the FI had the highest value relative to diagonal SPEMs. [Conclusion] SPEMs without head movement disrupt the stability of body balance in a static posture, and diagonal SPEMs may have a more negative effect in maintaining body balance than horizontal or vertical SPEMs. PMID- 27190479 TI - Immediate effects of kinematic taping on lower extremity muscle tone and stiffness in flexible flat feet. AB - [Purpose] This study aimed to examine the immediate effects of kinematic taping on the tone and stiffness in the leg muscles of subjects with flexible flat feet. [Subjects and Methods] A total of 30 subjects, 15 in the kinematic taping and 15 in the sham taping group, were administered respective taping interventions. Subsequently, the foot pressure and the tone and stiffness in the tibialis anterior, rectus femoris, medial gastrocnemius, and the long head of the biceps femoris muscles of both the lower extremities were measured. [Results] The foot pressure of the dominant leg significantly decreased in the kinematic taping group. The muscle tone and stiffness in the rectus femoris muscle of the dominant and non-dominant leg, tibialis anterior muscle of the dominant leg, medial gastrocnemius muscle of the non-dominant leg, and the stiffness in the dominant leg significantly decreased. The muscle tone and stiffness generally increased in the sham taping group. However, no significant difference was observed between the 2 groups. [Conclusion] This study demonstrated that kinematic taping on flexible flat feet had positive effects of immediately reducing the abnormally increased foot pressure and the tone and stiffness in the lower extremity muscles. PMID- 27190480 TI - Improvement in the physiological function and standing stability based on kinect multimedia for older people. AB - [Purpose] The increase in the Taiwanese older population is associated with age related inconveniences. Finding adequate and simple physical activities to help the older people maintaining their physiological function and preventing them from falls has become an urgent social issue. [Subjects and Methods] This study aimed to design a virtual exercise training game suitable for Taiwanese older people. This system will allow for the maintenance of the physiological function and standing stability through physical exercise, while using a virtual reality game. The participants can easily exercise in a carefree, interactive environment. This study will use Kinect for Windows for physical movement detection and Unity software for virtual world development. [Results] Group A and B subjects were involved in the exercise training method of Kinect interactive multimedia for 12 weeks. The results showed that the functional reach test and the unipedal stance test improved significantly. [Conclusion] The physiological function and standing stability of the group A subjects were examined at six weeks post training. The results showed that these parameters remained constant. This proved that the proposed system provide substantial support toward the preservation of the Taiwanese older people' physiological function and standing stability. PMID- 27190481 TI - Multimedia virtualized environment for shoulder pain rehabilitation. AB - [Purpose] Researchers imported games and virtual reality training to help participants train their shoulders in a relaxed environment. [Subjects and Methods] This study included the use of Kinect somatosensory device with Unity software to develop 3-dimensional situational games. The data collected from this training process can be uploaded via the Internet to a cloud or server for participants to perform self-inspection. The data can be a reference for the medical staff to assess training effectiveness for those with impairments and plan patient rehabilitation courses. [Results] In the training activities, 8 subjects with normal shoulder function demonstrated that the system has good stability and reproducibility. Six subjects with impaired shoulder underwent 6 weeks of training. During the third week of training, average performance stabilized. The t-test comparing 1-2 weeks to 3-4 weeks and 5-6 weeks showed significant differences. [Conclusion] Using games as training methods improved patient concentration, interest in participation and allowed patients to forget about their body discomfort. The equipment utilized in this study is inexpensive, easy to obtain, and the system is easy to install. People can perform simple self training both at home or in the office. PMID- 27190482 TI - Effects of aerobic exercise training on peripheral brain-derived neurotrophic factor and eotaxin-1 levels in obese young men. AB - [Purpose] The aim of the present study was to investigate the effects of aerobic exercise training on the levels of peripheral brain-derived neurotrophic factor and eotaxin-1 in obese young men. [Subjects and Methods] The subjects included sixteen obese young men with a body mass index greater than 25 kg/m(2). They were randomly divided between control and exercise groups (n = 8 in each group). The exercise group performed treadmill exercise for 40 min, 3 times a week for 8 weeks at the intensity of 70% heart rate reserve. Blood collection was performed to examine the levels of serum glucose, plasma malonaldehyde, serum brain-derived neurotrophic factor, and plasma eotaxin-1 before and after the intervention (aerobic exercise training). [Results] Following the intervention, serum BDNF levels were significantly higher, while serum glucose, plasma MDA, and plasma eotaxin-1 levels were significantly lower than those prior to the intervention in the exercise group. [Conclusion] Aerobic exercise training can induce neurogenesis in obese individuals by increasing the levels of brain-derived neurotrophic factor and reducing the levels of eotaxin-1. Alleviation of oxidative stress is possibly responsible for such changes. PMID- 27190483 TI - The effects of weekly exercise time on VO2max and resting metabolic rate in normal adults. AB - [Purpose] The present study examined the effect of individual weekly exercise time on resting metabolic rate and VO2max (maximal oxygen uptake), which are important components of individual health indexes. [Subjects and Methods] Thirty healthy adults participated in this study. Questionnaires were used to divide the participants into groups based on average weekly walking. Resting metabolic rate was measured using a respiratory gas analyzer. Graded exercise tests were conducted using a treadmill, and the modified Bruce protocol was used as an exercise test method. [Results] VO2max, anaerobic threshold, and resting metabolic rate were significantly different among the groups. [Conclusion] Average weekly exercise time affected VO2max, resting metabolic rate, and anaerobic threshold, all of which are indicators of individual physical ability and health. These values increased as the individual amount of exercise increased. In addition, VO2max, resting metabolic rate, and anaerobic threshold were found to be closely correlated. These findings were consistent with the results of similar previous studies. PMID- 27190484 TI - Reliability and validity of center of pressure measures for balance assessment in older adults. AB - [Purpose] This study was conducted to assess the reliability and validity of center of pressure-based parameters for balance assessment. [Subjects and Methods] Two hundred and forty older adults were evaluated using a force platform and the Berg Balance Scale at 1-week intervals. The intra-class correlation coefficient and the Pearson correlation coefficient were used to test reliability and validity respectively. [Results] The reliability of the 12 selected center of pressure measures was satisfactory (intra-class correlation coefficient = 0.75 0.99) and the validity between the parameters and the Berg Balance Scale was moderate to good (r = -0.62 to -0.88). [Conclusion] Center of pressure-based parameters are reliable and valid measures in older adults. PMID- 27190485 TI - The antalgic effects of non-invasive physical modalities on central post-stroke pain: a systematic review. AB - [Purpose] This study systematically reviewed the antalgic effects of non-invasive physical modalities (NIPMs) on central post-stroke pain (CPSP). [Subjects and Methods] Clinical studies were sought on September 2015 in 10 electronic databases, including Medline and Scopus. The searching strings were "central pain and stroke" and "treatment, and physical or non-pharmacological". The inclusion and exclusion criteria were set for screening the clinical articles by two reviewers. Pain scores on visual analog scale in an article were used as the outcome measure for resulting judgment. The NIPMs intervention summarized from the eligible articles was rated from Levels A to C according to Evidence Classification Scheme for Therapeutic Interventions. [Results] Over 1200 articles were identified in the initial searches and 85 studies were retrieved. Sixteen studies were eligible and judged. Caloric vestibular stimulation (n=3), heterotopic noxious conditioning stimulation (n=1), and transcutaneous electrical stimulation (n=1) were rated below Level C. Transcranial direct current stimulation (TDCS; n=2) and transcranial magnetic stimulation (TMS; n=9) were rated as Level B. [Conclusion] The findings suggest that TMS and TDCS were better than other treatments for CPSP relief but the studies were of insufficient quality. PMID- 27190487 TI - Promotion and support of physical activity in elderly patients on hemodialysis: a case study. AB - [Purpose] The aim of this study was to ascertain the optimum strategy for implementing a physical activity intervention in patients on hemodialysis by investigating the physical characteristics of elderly patients on hemodialysis, and their attitude to physical activity and level of daily activity. [Subjects] The Subject were 10 elderly patients on hemodialysis. [Methods] They wore a physical activity monitor for 1 week. Data obtained were analyzed for hemodialysis and non- hemodialysis days, and two-way analysis of variance was used to compare the number of steps and activity levels. A questionnaire was administered to investigate the stage of psychological preparedness for exercise and attitudes toward/awareness of exercise. [Results] There was no significant difference in the number of steps or exercise levels on hemodialysis and non- hemodialysis days. However, on both types of days, subjects spent long periods not engaged in any activity. Most of their activity was either inactivity or sedentary behavior. [Conclusion] Patients on hemodialysis with low physical activity levels are considered to have poor physical function and exercise tolerance. To maintain and improve the physical function of patients on hemodialysis, it will be necessary to reduce their time spent in inactive, and comprehensive care that covers psychosocial aspects should be provided to promote the proactive improvement of physical activity and their attitudes to exercise. PMID- 27190486 TI - Effect of absence of vision on posture. AB - [Purpose] The visual system is one of the sensory systems that enables the body to assess and process information about the external environment. In the absence of vision, a blind person loses contact with the outside world and develops faulty motor patterns, which results in postural deficiencies. However, literature regarding the development of such deficiencies is limited. The aim of this study was to discuss the effect of absence of vision on posture, the possible biomechanics behind the resulting postural deficiencies, and strategies to correct and prevent them. [Subjects and Methods] Various electronic databases including PubMed, Medline, and Google scholar were examined using the words "body", "posture", "blind" and "absence of vision". References in the retrieved articles were also examined for cross-references. The search was limited to articles in the English language. [Results] A total of 74 papers were shortlisted for this review, most of which dated back to the 1950s and 60s. [Conclusion] Blind people exhibit consistent musculoskeletal deformities. Absence of vision leads to numerous abnormal sensory and motor interactions that often limit blind people in isolation. Rehabilitation of the blind is a multidisciplinary task. Specialists from different fields need to diagnose and treat the deficiencies of the blind together as a team. Before restoring the normal mechanics of posture and gait, the missing link with the external world should be reestablished. PMID- 27190488 TI - The effect of task-oriented training on the muscle activation of the upper extremity in chronic stroke patients. AB - [Purpose] The aim of this study was to determine the effects of task-oriented training on upper extremity muscle activation in daily activities performed by chronic stoke patients. [Subjects and Methods] In this research, task-oriented training was conducted by 2 chronic hemiplegic stroke patients. Task-oriented training was conducted 5 times a week, 30 minutes per day, for 2 weeks. Evaluation was conducted 3 times before and after the intervention. The Change of muscle activation in the upper extremity was measured using a BTS FreeEMG 300. [Results] The subjects' root mean square values for agonistic muscles for the reaching activity increased after the intervention. All subjects' co-coordination ratios decreased after the intervention in all movements of reaching activity. [Conclusion] Through this research, task-oriented training was proven to be effective in improving the muscle activation of the upper extremity in chronic hemiplegic stroke patients. PMID- 27190489 TI - Clinical usefulness of augmented reality using infrared camera based real-time feedback on gait function in cerebral palsy: a case study. AB - [Purpose] This study investigated the effects of real-time feedback using infrared camera recognition technology-based augmented reality in gait training for children with cerebral palsy. [Subjects] Two subjects with cerebral palsy were recruited. [Methods] In this study, augmented reality based real-time feedback training was conducted for the subjects in two 30-minute sessions per week for four weeks. Spatiotemporal gait parameters were used to measure the effect of augmented reality-based real-time feedback training. [Results] Velocity, cadence, bilateral step and stride length, and functional ambulation improved after the intervention in both cases. [Conclusion] Although additional follow-up studies of the augmented reality based real-time feedback training are required, the results of this study demonstrate that it improved the gait ability of two children with cerebral palsy. These findings suggest a variety of applications of conservative therapeutic methods which require future clinical trials. PMID- 27190490 TI - Optimizing physical therapy for ankylosing spondylitis: a case study in a young football player. AB - [Purpose] Ankylosing spondylitis is prevalent in men. Modern and expert consensus documents include physical therapy among the strategies for the treatment of ankylosing spondylitis. This study aimed to describe the physical therapy approach in an athlete with ankylosing spondylitis. [Subject and Methods] The patient, refractory to treatment with anti-inflammatory medication, showed pelvic and lumbar pain and joint, muscle, and functional disorders, which were treated with orthopedic joint mobilization, dry needling, exercise, and whole-body hyperthermia. [Results] After the treatment, pain relief, normal joint mobility, improved muscle function, and return to activities of daily living and competitive sporting activities were recorded. [Conclusion] The literature provides evidence for the use of joint mobilization techniques; however, no previous studies have used the same techniques and methods. There is no previous evidence for the use of dry needling in this pathology. Exercise therapy has a higher level of evidence, and guidelines with scientific support were followed. This research confirms the effectiveness of hyperthermia for arthritis. The early stage of ankylosing spondylitis, and the young age, good overall condition, and cooperative attitude of the patient led to positive outcomes. In conclusion, a favorable response that promoted the remission of the disease was observed. PMID- 27190492 TI - Histamine and Immune Biomarkers in CNS Disorders. AB - Neuroimmune dysregulation is a common phenomenon in different forms of central nervous system (CNS) disorders. Cross-links between central and peripheral immune mechanisms appear to be disrupted as reflected by a series of immune markers (CD3, CD4, CD7, HLA-DR, CD25, CD28, and CD56) which show variability in brain disorders such as anxiety, depression, psychosis, stroke, Alzheimer's disease, Parkinson's disease, attention-deficit hyperactivity disorder, migraine, epilepsy, vascular dementia, mental retardation, cerebrovascular encephalopathy, multiple sclerosis, brain tumors, cranial nerve neuropathies, mental retardation, and posttraumatic brain injury. Histamine (HA) is a pleiotropic monoamine involved in several neurophysiological functions, neuroimmune regulation, and CNS pathogenesis. Changes in brain HA show an age- and sex-related pattern, and alterations in brain HA levels are present in different CNS regions of patients with Alzheimer's disease (AD). Brain HA in neuronal and nonneuronal compartments plays a dual role (neurotrophic versus neurotoxic) in a tissue-specific manner. Pathogenic mechanisms associated with neuroimmune dysregulation in AD involve HA, interleukin-1beta, and TNF-alpha, whose aberrant expression contributes to neuroinflammation as an aggravating factor for neurodegeneration and premature neuronal death. PMID- 27190491 TI - Association between Serum Interleukin-17A Level and High-Altitude Deacclimatization Syndrome. AB - High-altitude deacclimatization syndrome (HADAS) is emerging as a severe public health issue that threatens the quality of life of individuals who return to lower altitude from high altitude. In this study, we measured serum levels of SOD, MDA, IL-17A, IL-10, TNF-alpha, and HADAS score in HADAS subjects at baseline and 50th and 100th days and to evaluate the relationship between interleukins, including IL-17A, and HADAS. Our data showed that and the serum IL-17A levels and HADAS score decreased over time in the HADAS group, and serum IL-17A levels were significantly higher in the HADAS group at baseline and 50th day compared with controls (p < 0.05). Furthermore, baseline serum levels of MDA and TNF-alpha were significantly higher, while SOD and IL-10 levels were lower in HADAS subjects compared with controls (p < 0.05). It is interesting that serum levels of IL-17A were clearly interrelated with HADAS incidence and severity (p < 0.05). ROC curve analysis showed that combined serum IL-17A and IL-10 levels were a better predictor of HADAS incidence than serum levels of IL-17A or IL-10 alone. These data suggest that serum levels of IL-17A are a novel predictive index of HADAS. PMID- 27190494 TI - Long-range forces affecting equilibrium inertial focusing behavior in straight high aspect ratio microfluidic channels. AB - The controlled and directed focusing of particles within flowing fluids is a problem of fundamental and technological significance. Microfluidic inertial focusing provides passive and precise lateral and longitudinal alignment of small particles without the need for external actuation or sheath fluid. The benefits of inertial focusing have quickly enabled the development of miniaturized flow cytometers, size-selective sorting devices, and other high-throughput particle screening tools. Straight channel inertial focusing device design requires knowledge of fluid properties and particle-channel size ratio. Equilibrium behavior of inertially focused particles has been extensively characterized and the constitutive phenomena described by scaling relationships for straight channels of square and rectangular cross section. In concentrated particle suspensions, however, long-range hydrodynamic repulsions give rise to complex particle ordering that, while interesting and potentially useful, can also dramatically diminish the technique's effectiveness for high-throughput particle handling applications. We have empirically investigated particle focusing behavior within channels of increasing aspect ratio and have identified three scaling regimes that produce varying degrees of geometrical ordering between focused particles. To explore the limits of inertial particle focusing and identify the origins of these long-range interparticle forces, we have explored equilibrium focusing behavior as a function of channel geometry and particle concentration. Experimental results for highly concentrated particle solutions identify equilibrium thresholds for focusing that scale weakly with concentration and strongly with channel geometry. Balancing geometry mediated inertial forces with estimates for interparticle repulsive forces now provide a complete picture of pattern formation among concentrated inertially focused particles and enhance our understanding of the fundamental limits of inertial focusing for technological applications. PMID- 27190493 TI - Walker 256 Tumor Growth Suppression by Crotoxin Involves Formyl Peptide Receptors and Lipoxin A4. AB - We investigated the effects of Crotoxin (CTX), the main toxin of South American rattlesnake (Crotalus durissus terrificus) venom, on Walker 256 tumor growth, the pain symptoms associated (hyperalgesia and allodynia), and participation of endogenous lipoxin A4. Treatment with CTX (s.c.), daily, for 5 days reduced tumor growth at the 5th day after injection of Walker 256 carcinoma cells into the plantar surface of adult rat hind paw. This observation was associated with inhibition of new blood vessel formation and decrease in blood vessel diameter. The treatment with CTX raised plasma concentrations of lipoxin A4 and its natural analogue 15-epi-LXA4, an effect mediated by formyl peptide receptors (FPRs). In fact, the treatment with Boc-2, an inhibitor of FPRs, abolished the increase in plasma levels of these mediators triggered by CTX. The blockage of these receptors also abolished the inhibitory action of CTX on tumor growth and blood vessel formation and the decrease in blood vessel diameter. Together, the results herein presented demonstrate that CTX increases plasma concentrations of lipoxin A4 and 15-epi-LXA4, which might inhibit both tumor growth and formation of new vessels via FPRs. PMID- 27190495 TI - A Therapeutic Role for Survivin in Mitigating the Harmful Effects of Ionizing Radiation. AB - Background. Radiation therapy is a form of adjuvant care used in many oncological treatment protocols. However, nonmalignant neighboring tissues are harmed as a result of this treatment. Therefore, the goal of this study was to induce the production of survivin, an antiapoptotic protein, to determine if this protein could provide protection to noncancerous cells during radiation exposure. Methods. Using a murine model, a recombinant adenoassociated virus (rAAV) was used to deliver survivin to the treatment group and yellow fluorescence protein (YFP) to the control group. Both groups received targeted radiation. Visual inspection, gait analysis, and tissue histology were used to determine the extent of damage caused by the radiation. Results. The YFP group demonstrated ulceration of the irradiated area while the survivin treated mice exhibited only hair loss. Histology showed that the YFP treated mice experienced dermal thickening, as well as an increase in collagen that was not present in the survivin treated mice. Gait analysis demonstrated a difference between the two groups, with the YFP mice averaging a lower speed. Conclusions. The use of gene-modification to induce survivin expression in normal tissues allows for the protection of nontarget areas from the negative side effects normally associated with ionizing radiation. PMID- 27190496 TI - A case report of autoimmune necrotizing myositis presenting as dysphagia and neck swelling. AB - BACKGROUND: Severe dysphagia may occur in the immune mediated necrotizing myopathies (IMNM). Neck swelling and severe dysphagia as the initial symptoms upon presentation has not been previously described. CASE PRESENTATION: A 55-year old male with a 4 week history of neck swelling, fatigue, dysphagia, myalgias, night sweats, and cough was admitted for an elevated CK. He underwent extensive infectious and inflammatory evaluation including neck imaging and muscle biopsy. Neck CT and MRI showed inflammation throughout his strap muscles, retropharyngeal soft tissues and deltoids. Infectious work up was negative. Deltoid muscle biopsy demonstrated evidence of IMNM. Lab tests revealed anti-3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) antibodies confirming the diagnosis of HMGCR IMNM. CONCLUSIONS: HMGCR IMNM is a rare and incompletely understood disease process. Awareness of HMGCR IMNM could potentially lead to earlier diagnosis, treatment and improved clinical outcomes as disease progression can be rapid and severe. PMID- 27190497 TI - Effects of CpG Oligodeoxynucleotide 1826 on transforming growth factor-beta 1 and radiation-induced pulmonary fibrosis in mice. AB - BACKGROUND: Cytosine-phosphate-guanine (CpG) oligodeoxyribonucleotides (ODNs) are synthetic DNA fragments containing unmethylated cytosine-guanine motifs with potential immune modulatory effects and have recently been suggested to enhance sensitivity to traditional therapies in lung cancer. This study aimed to examine the effects of CpG ODN1826 on transforming growth factor-beta 1(TGF-beta1) and radiation-induced pulmonary fibrosis in mice. METHODS: The radiation-induced pulmonary fibrosis mouse model was established by a single dose of 20 Gy, 6 MV X rays exposure to the left lung. ICR mice were evenly randomized into four groups, comprising: a control group, a radiation group (RT group), a CpG group and a radiation combined with CpG ODN1826 group (RT + CpG group), with 40 mice in each group. CpG ODN1826 was intraperitoneally injected into mice at 1, 3, 5, 7 and 9 d post-irradiation. The mice were sacrificed at 1, 5, 15, 30 and 90 d post irradiation. Paraffin sections of the radiated lung were subjected to H&E staining and Masson staining. The Ashcroft scale was used for quantitative histological analysis of fibrotic changes induced by irradiation. Concentrations of serum TGF-beta1 were determined by ELISA, and concentrations of Hydroxyproline(Hyp) in the lung were determined with the alkaline hydrolysis method. Relative gene expression of FoxP3 was determined by real-time PCR. RESULTS: The radiation-induced pulmonary fibrosis mouse model was successfully established. The serum concentrations of TGF -beta1 of RT group were higher than those of the RT + CpG group (t = 5.212, 7.126, 7.972 and 3.785, P < 0.05). The Hyp in the lung of RT group was higher than that of RT + CpG group (t = 4.606, P < 0.05). The relative expressions of FoxP3 gene in the lung of the RT group were higher than those of RT + CpG group (t = 8.395, 5.099 and 6.147, P < 0.05). CONCLUSIONS: CpG ODN1826 could reduce the serum concentrations of TGF-beta1 and the lung content of Hyp in radiation-induced pulmonary fibrosis, which might be related to the possibility that CpG ODN1826 can reduce expression of the FoxP3 gene. PMID- 27190499 TI - Behavioral alterations induced by repeated saxitoxin exposure in drinking water. AB - BACKGROUND: Blooms of the saxitoxin-producing cyanobacterium Cylindrospermopsis raciborskii have been contaminating drinking water reservoirs in Brazil for many years. Although acute effects of saxitoxin intoxication are well known, chronic deleterious outcomes caused by repeated saxitoxin exposure still require further investigation. The aim of the present work is to investigate the effects of consumption of drinking water contaminated with C. raciborskii for 30 days on learning and memory processes in rats. METHODS: The effects of saxitoxin (3 or 9 MUg/L STX equivalents) or cyanobacteria on behavior was determined using the open field habituation task, elevated plus maze anxiety model task, inhibitory avoidance task, and referential Morris water maze task. RESULTS: No effects of saxitoxin consumption was observed on anxiety and motor exploratory parameters in the elevated plus maze and open field habituation tasks, respectively. However, groups treated with 9 MUg/L STX equivalents displayed a decreased memory performance in the inhibitory avoidance and Morris water maze tasks. CONCLUSIONS: These results suggest an amnesic effect of saxitoxin on aversive and spatial memories. PMID- 27190502 TI - Global Exponential Stability of Almost Periodic Solution for Neutral-Type Cohen Grossberg Shunting Inhibitory Cellular Neural Networks with Distributed Delays and Impulses. AB - A kind of neutral-type Cohen-Grossberg shunting inhibitory cellular neural networks with distributed delays and impulses is considered. Firstly, by using the theory of impulsive differential equations and the contracting mapping principle, the existence and uniqueness of the almost periodic solution for the above system are obtained. Secondly, by constructing a suitable Lyapunov functional, the global exponential stability of the unique almost periodic solution is also investigated. The work in this paper improves and extends some results in recent years. As an application, an example and numerical simulations are presented to demonstrate the feasibility and effectiveness of the main results. PMID- 27190501 TI - Timcodar (VX-853) Is a Non-FKBP12 Binding Macrolide Derivative That Inhibits PPARgamma and Suppresses Adipogenesis. AB - Nutrient overload and genetic factors have led to a worldwide epidemic of obesity that is the underlying cause of diabetes, atherosclerosis, and cardiovascular disease. In this study, we used macrolide drugs such as FK506, rapamycin, and macrolide derived, timcodar (VX-853), to determine their effects on lipid accumulation during adipogenesis. Rapamycin and FK506 bind to FK506-binding proteins (FKBPs), such as FKBP12, which causes suppression of the immune system and inhibition of mTOR. Rapamycin has been previously reported to inhibit the adipogenic process and lipid accumulation. However, rapamycin treatment in rodents caused immune suppression and glucose resistance, even though the mice lost weight. Here we show that timcodar (1 MUM), a non-FKBP12-binding drug, significantly (p < 0.001) inhibited lipid accumulation during adipogenesis. A comparison of the same concentration of timcodar (1 MUM) and rapamycin (1 MUM) showed that both are inhibitors of lipid accumulation during adipogenesis. Importantly, timcodar potently (p < 0.01) suppressed transcriptional regulators of adipogenesis, PPARgamma and C/EBPalpha, resulting in the inhibition of genes involved in lipid accumulation. These studies set the stage for timcodar as a possible antiobesity therapy, which is rapidly emerging as a pandemic. PMID- 27190500 TI - 15-Deoxy-Delta(12,14)-prostaglandin J2 Induces Apoptosis and Upregulates SOCS3 in Human Thyroid Cancer Cells. AB - The cyclopentenone prostaglandin 15-deoxy-Delta(12,14)-prostaglandin J2 (15d PGJ2) is a natural ligand of peroxisome proliferator-activated receptor gamma (PPAR-gamma) and a potential mediator of apoptosis in cancer cells. In the present study, we evaluated the effect of 15d-PGJ2 in human thyroid papillary carcinoma cells (TPC-1) using different doses of 15d-PGJ2 (0.6 to 20 MUM) to determine IC50 (9.3 MUM) via the MTT assay. The supernatant culture medium of the TPC-1 cells that was treated either with 15d-PGJ2 or with vehicle (control) for 24 hours was assessed for IL-6 secretion via CBA assay. RT-qPCR was used to evaluate mRNA expression of IL-6, SOCS1, SOCS3, and STAT3. TPC-1 cells treated with 15d-PGJ2 decreased the secretion and expression of IL-6 and STAT3, while it increased SOCS1 and SOCS3. Overall, we demonstrated that 15d-PGJ2 downregulated IL-6 signaling pathway and led TPC-1 cells into apoptosis. In conclusion, 15d PGJ2 shows the potential to become a new therapeutic approach for thyroid tumors. PMID- 27190503 TI - An Interactive Astronaut-Robot System with Gesture Control. AB - Human-robot interaction (HRI) plays an important role in future planetary exploration mission, where astronauts with extravehicular activities (EVA) have to communicate with robot assistants by speech-type or gesture-type user interfaces embedded in their space suits. This paper presents an interactive astronaut-robot system integrating a data-glove with a space suit for the astronaut to use hand gestures to control a snake-like robot. Support vector machine (SVM) is employed to recognize hand gestures and particle swarm optimization (PSO) algorithm is used to optimize the parameters of SVM to further improve its recognition accuracy. Various hand gestures from American Sign Language (ASL) have been selected and used to test and validate the performance of the proposed system. PMID- 27190504 TI - The Hepaticojejunostomy Technique with Intra-Anastomotic Stent in Biliary Diseases and Its Evolution throughout the Years: A Technical Analysis. AB - Roux-en-Y hepaticojejunostomy (RYHJ) is currently considered as the definitive treatment for iatrogenic bile duct injuries and the principal representative of biliary diversion procedures. This technique has met many milestones of extensive evolution, particularly the last years of concomitant technological evolution (laparoscopic/robotic approach). Anastomotic strictures and leaks, which may have deleterious effects on the survival and quality of life of a patient with biliary obstruction of any cause, made the need of the development of a safe and efficient RYHJ compulsory. The aim of this technical analysis and the juxtaposed discussions is to elucidate with the most important milestones and technical tips and tricks all aspects of a feasible and reliable RYHJ technique that is performed in our center for the last 25 years in around 400 patients. PMID- 27190506 TI - A Multiple-Classifier Framework for Parkinson's Disease Detection Based on Various Vocal Tests. AB - Recently, speech pattern analysis applications in building predictive telediagnosis and telemonitoring models for diagnosing Parkinson's disease (PD) have attracted many researchers. For this purpose, several datasets of voice samples exist; the UCI dataset named "Parkinson Speech Dataset with Multiple Types of Sound Recordings" has a variety of vocal tests, which include sustained vowels, words, numbers, and short sentences compiled from a set of speaking exercises for healthy and people with Parkinson's disease (PWP). Some researchers claim that summarizing the multiple recordings of each subject with the central tendency and dispersion metrics is an efficient strategy in building a predictive model for PD. However, they have overlooked the point that a PD patient may show more difficulty in pronouncing certain terms than the other terms. Thus, summarizing the vocal tests may lead into loss of valuable information. In order to address this issue, the classification setting must take what has been said into account. As a solution, we introduced a new framework that applies an independent classifier for each vocal test. The final classification result would be a majority vote from all of the classifiers. When our methodology comes with filter-based feature selection, it enhances classification accuracy up to 15%. PMID- 27190505 TI - Effect of Interval between Neoadjuvant Chemoradiotherapy and Surgery on Oncological Outcome for Rectal Cancer: A Systematic Review and Meta-Analysis. AB - Aim. To evaluate the influence of interval between neoadjuvant chemoradiotherapy (NCRT) and surgery on oncological outcome. Methods. A systematic search was conducted in PubMed, the Cochrane Library, and Embase databases for publications reporting oncological outcomes of patients following rectal cancer surgery performed at different NCRT-surgery intervals. Relative risk (RR) of pathological complete response (pCR) among different intervals was pooled. Results. Fifteen retrospective cohort studies representing 4431 patients met the inclusion criteria. There was a significantly increased rate of pCR in patients treated with surgery followed 7 or 8 weeks later (RR, 1.45; 95% CI, 1.18-1.78; and P < 0.01 and RR, 1.49; 95% CI, 1.15-1.92; and P = 0.002, resp.). There is no consistent evidence of improved local control or overall survival with longer or shorter intervals. Conclusion. Performing surgery 7-8 weeks after the end of NCRT results in the highest chance of achieving pCR. For candidates of abdominoperineal resection before NCRT, these data support implementation of prolonging the interval after NCRT to optimize the chances of pCR and perhaps add to the possibility of ultimate organ preservation. PMID- 27190507 TI - Software-Assisted Depth Analysis of Optic Nerve Stereoscopic Images in Telemedicine. AB - Background. Software guided optic nerve assessment can assist in process automation and reduce interobserver disagreement. We tested depth analysis software (DAS) in assessing optic nerve cup-to-disc ratio (VCD) from stereoscopic optic nerve images (SONI) of normal eyes. Methods. In a prospective study, simultaneous SONI from normal subjects were collected during telemedicine screenings using a Kowa 3Wx nonmydriatic simultaneous stereoscopic retinal camera (Tokyo, Japan). VCD was determined from SONI pairs and proprietary pixel DAS (Kowa Inc., Tokyo, Japan) after disc and cup contour line placement. A nonstereoscopic VCD was determined using the right channel of a stereo pair. Mean, standard deviation, t-test, and the intraclass correlation coefficient (ICCC) were calculated. Results. 32 patients had mean age of 40 +/- 14 years. Mean VCD on SONI was 0.36 +/- 0.09, with DAS 0.38 +/- 0.08, and with nonstereoscopic 0.29 +/- 0.12. The difference between stereoscopic and DAS assisted was not significant (p = 0.45). ICCC showed agreement between stereoscopic and software VCD assessment. Mean VCD difference was significant between nonstereoscopic and stereoscopic (p < 0.05) and nonstereoscopic and DAS (p < 0.005) recordings. Conclusions. DAS successfully assessed SONI and showed a high degree of correlation to physician-determined stereoscopic VCD. PMID- 27190508 TI - Ebolavirus Database: Gene and Protein Information Resource for Ebolaviruses. AB - Ebola Virus Disease (EVD) is a life-threatening haemorrhagic fever in humans. Even though there are many reports on EVD, the protein precursor functions and virulent factors of ebolaviruses remain poorly understood. Comparative analyses of Ebolavirus genomes will help in the identification of these important features. This prompted us to develop the Ebolavirus Database (EDB) and we have provided links to various tools that will aid researchers to locate important regions in both the genomes and proteomes of Ebolavirus. The genomic analyses of ebolaviruses will provide important clues for locating the essential and core functional genes. The aim of EDB is to act as an integrated resource for ebolaviruses and we strongly believe that the database will be a useful tool for clinicians, microbiologists, health care workers, and bioscience researchers. PMID- 27190509 TI - Feature Selection Has a Large Impact on One-Class Classification Accuracy for MicroRNAs in Plants. AB - MicroRNAs (miRNAs) are short RNA sequences involved in posttranscriptional gene regulation. Their experimental analysis is complicated and, therefore, needs to be supplemented with computational miRNA detection. Currently computational miRNA detection is mainly performed using machine learning and in particular two-class classification. For machine learning, the miRNAs need to be parametrized and more than 700 features have been described. Positive training examples for machine learning are readily available, but negative data is hard to come by. Therefore, it seems prerogative to use one-class classification instead of two-class classification. Previously, we were able to almost reach two-class classification accuracy using one-class classifiers. In this work, we employ feature selection procedures in conjunction with one-class classification and show that there is up to 36% difference in accuracy among these feature selection methods. The best feature set allowed the training of a one-class classifier which achieved an average accuracy of ~95.6% thereby outperforming previous two-class-based plant miRNA detection approaches by about 0.5%. We believe that this can be improved upon in the future by rigorous filtering of the positive training examples and by improving current feature clustering algorithms to better target pre-miRNA feature selection. PMID- 27190510 TI - Molecular Docking and In Silico ADMET Study Reveals Acylguanidine 7a as a Potential Inhibitor of beta-Secretase. AB - Amyloidogenic pathway in Alzheimer's disease (AD) involves breakdown of APP by beta-secretase followed by gamma-secretase and results in formation of amyloid beta plaque. beta-secretase has been a promising target for developing novel anti Alzheimer drugs. To test different molecules for this purpose, test ligands like acylguanidine 7a, rosiglitazone, pioglitazone, and tartaric acid were docked against our target protein beta-secretase enzyme retrieved from Protein Data Bank, considering MK-8931 (phase III trial, Merck) as the positive control. Docking revealed that, with respect to their free binding energy, acylguanidine 7a has the lowest binding energy followed by MK-8931 and pioglitazone and binds significantly to beta-secretase. In silico ADMET predictions revealed that except tartaric acid all other compounds had minimal toxic effects and had good absorption as well as solubility characteristics. These compounds may serve as potential lead compound for developing new anti-Alzheimer drug. PMID- 27190511 TI - FGF21 Is Associated with Acanthosis Nigricans in Obese Patients. AB - Objective. We aimed to investigate the relationship between FGF21 and obesity related acanthosis nigricans (AN). Methods. 40 obese patients without AN (OB group), 40 obese patients with AN (AN group), and 40 healthy volunteers (control group, CON) were included in this study. Weight, BMI, lipid profile, FFA, UA, and CRP were measured in all participants. Oral glucose tolerance tests (OGTT) were performed and serum glucose and plasma insulin were measured. Serum FGF21 was measured by ELISA. Results. Compared with OB group, AN group had higher levels of fasting insulin and homeostasis model of assessment for insulin resistance (HOMA IR) (P < 0.05), but lower serum levels of blood glucose. The difference of FGF21 among three groups was significant and AN group showed the highest serum level of FGF21 (P < 0.05). Serum FGF21 was most positively correlated with fasting insulin and HOMA-IR. Multiple logistic analysis showed that FGF21 was the independent risk factor for AN (OR 4.550; 95% CI 1.054-19.635; P = 0.042). Conclusion. AN patients had more serious hyperinsulinemia but better serum levels of blood glucose than OB. Increased FGF21 is associated with AN in obese patients and may be considered as compensatory response to the decreased insulin sensitivity. PMID- 27190512 TI - Growth Hormone Therapy Benefits Pituitary Stalk Interruption Syndrome Patients with Short Stature: A Retrospective Study of 75 Han Chinese. AB - Objective. We aim to investigate the long-term benefits of growth hormone (GH) therapy in short stature adolescents and adults with pituitary stalk interruption syndrome (PSIS), which would be beneficial for future clinical applications. Design and Methods. In this study, initial height, final height, total height gain, and GH treatment history were retrospectively investigated in 75 Chinese PSIS patients. We compared height gain between the GH treated cohort and untreated cohort and explored the impact of different GH therapy duration on height gain. Results. For GH treated patients, their final height (SDS) increased from -1.99 +/- 1.91 (-6.93~2.80) at bone age (BA) of 11.2 (5.0~17.0) years to 1.47 +/- 1.64 (-7.82~1.05) at BA of 16.6 (8.0~18.0) years (P = 0.016). And GH treated patients had more height gain than the untreated patients (P < 0.05). There was a significant difference between the different GH therapy duration groups (P = 0.001): GH 0 versus GH 3, P = 0.000; GH 1 versus GH 3, P = 0.028; GH 2 versus GH 3, P = 0.044. Conclusion. Adult Chinese PSIS patients with short stature benefited the most from at least 12 months of GH therapy. Although patient diagnosis age was lagged behind in the developing countries, GH treatment was still effective for them and resulted in a higher final height and more height gain. PMID- 27190513 TI - Ghrelin Protects against Dexamethasone-Induced INS-1 Cell Apoptosis via ERK and p38MAPK Signaling. AB - Glucocorticoid excess induces apoptosis of islet cells, which may result in diabetes. In this study, we investigated the protective effect of ghrelin on dexamethasone-induced INS-1 cell apoptosis. Our data showed that ghrelin (0.1 MUM) inhibited dexamethasone-induced (0.1 MUM) apoptosis of INS-1 cells and facilitated cell proliferation. Moreover, ghrelin upregulated Bcl-2 expression, downregulated Bax expression, and decreased caspase-3 activity. The protective effect of ghrelin against dexamethasone-induced INS-1 cell apoptosis was mediated via growth hormone secretagogue receptor 1a. Further studies revealed that ghrelin increased ERK activation and decreased p38MAPK expression after dexamethasone treatment. Ghrelin-mediated protection of dexamethasone-induced apoptosis of INS-1 cells was attenuated using the ERK inhibitor U0126 (10 MUM), and cell viability increased using the p38MAPK inhibitor SB203580 (10 MUM). In conclusion, ghrelin could protect against dexamethasone-induced INS-1 cell apoptosis, at least partially via GHS-R1a and the signaling pathway of ERK and p38MAPK. PMID- 27190514 TI - Maternal and Fetal Lipid and Adipokine Profiles and Their Association with Obesity. AB - Background. Maternal metabolic changes impact fetal metabolism resulting in a higher risk for developing chronic diseases later in life. The aim of this study was to assess the association between maternal and fetal adipokine and lipid profiles, as well as the influence of maternal weight on this association. Methods. Healthy pregnant women at term who delivered by C-section were enrolled. Maternal and fetal glucose, lipid profile, adiponectin, leptin, and resistin levels were analyzed by obesity and maternal weight gain. Statistics included descriptives, correlations, and mean differences (SPSS v20.0). Results. Adiponectin and resistin concentrations were higher in fetal blood, while leptin was lower (p < 0.05). A significant inverse association between maternal resistin and fetal LDL-cholesterol (LDL-C) (r = -0.327; p = 0.022) was observed. A positive correlation was found between maternal and fetal resistin (r = 0.358; p = 0.013). Women with excessive weight gain had higher leptin levels and their fetuses showed higher LDL-C levels (p < 0.05). Conclusions. Maternal resistin showed an inverse association with fetal LDL-C, suggesting that maternal adiposity status may play an active role in the regulation of fetal lipid profile and consequently, in fetal programming. Excessive maternal weight gain during pregnancy may exert an effect over metabolic mediators in both mother and newborn. PMID- 27190515 TI - Tetrahydro-iso-alpha Acids Antagonize Estrogen Receptor Alpha Activity in MCF-7 Breast Cancer Cells. AB - Tetrahydro-iso-alpha acids commonly called THIAA or Tetra are modified hop acids extracted from hop (Humulus lupulus L.) which are frequently used in brewing industry mainly in order to provide beer bitterness and foam stability. Interestingly, molecular structure of tetrahydro-iso-alpha acids is close to a new type of estrogen receptor alpha (ERalpha) antagonists aimed at disrupting the binding of coactivators containing an LxxLL motif (NR-box). In this work we show that THIAA decreases estradiol-stimulated proliferation of MCF-7 (ERalpha positive breast cancer cells). Besides, we show that it inhibits ERalpha transcriptional activity. Interestingly, this extract fails to compete with estradiol for ERalpha binding and does not significantly impact the receptor turnover rate in MCF-7 cells, suggesting that it does not act like classical antiestrogens. Hence, we demonstrate that THIAA is able to antagonize ERalpha estradiol-induced recruitment of the LxxLL binding motif. PMID- 27190516 TI - Minimally Invasive Alveolar Ridge Preservation Utilizing an In Situ Hardening beta-Tricalcium Phosphate Bone Substitute: A Multicenter Case Series. AB - Ridge preservation measures, which include the filling of extraction sockets with bone substitutes, have been shown to reduce ridge resorption, while methods that do not require primary soft tissue closure minimize patient morbidity and decrease surgical time and cost. In a case series of 10 patients requiring single extraction, in situ hardening beta-tricalcium phosphate (beta-TCP) granules coated with poly(lactic-co-glycolic acid) (PLGA) were utilized as a grafting material that does not necessitate primary wound closure. After 4 months, clinical observations revealed excellent soft tissue healing without loss of attached gingiva in all cases. At reentry for implant placement, bone core biopsies were obtained and primary implant stability was measured by final seating torque and resonance frequency analysis. Histological and histomorphometrical analysis revealed pronounced bone regeneration (24.4 +/- 7.9% new bone) in parallel to the resorption of the grafting material (12.9 +/- 7.7% graft material) while high levels of primary implant stability were recorded. Within the limits of this case series, the results suggest that beta-TCP coated with polylactide can support new bone formation at postextraction sockets, while the properties of the material improve the handling and produce a stable and porous bone substitute scaffold in situ, facilitating the application of noninvasive surgical techniques. PMID- 27190517 TI - Cuspal Displacement Induced by Bulk Fill Resin Composite Polymerization: Biomechanical Evaluation Using Fiber Bragg Grating Sensors. AB - Polymerization shrinkage is a major concern to the clinical success of direct composite resin restorations. The aim of this study was to compare the effect of polymerization shrinkage strain of two resin composites on cuspal movement based on the use of fiber Bragg grating (FBG) sensors. Twenty standardized Class II cavities prepared in upper third molars were allocated into two groups (n = 10). Restorations involved the bulk fill placement of conventional microhybrid resin composite (Esthet*X(r) HD, Dentsply DeTrey) (Group 1) or flowable "low-shrinkage" resin composite (SDRTM, Dentsply DeTrey) (Group 2). Two FBG sensors were used per restoration for real-time measurement of cuspal linear deformation and temperature variation. Group comparisons were determined using ANCOVA (alpha = 0.05) considering temperature as the covariate. A statistically significant correlation between cuspal deflection, time, and material was observed (p < 0.01). Cuspal deflection reached 8.8 MUm (0.23%) and 7.8 MUm (0.20%) in Groups 1 and 2, respectively. When used with bulk fill technique, flowable resin composite SDRTM induced significantly less cuspal deflection than the conventional resin composite Esthet*X(r) HD (p = 0.015) and presented a smoother curve slope during the polymerization. FBG sensors appear to be a valid tool for accurate real-time monitoring of cuspal deformation. PMID- 27190518 TI - Detection of Extended-Spectrum Beta-Lactamase-Producing Escherichia coli in Market-Ready Chickens in Zambia. AB - The frequent administering of antibiotics in the treatment of poultry diseases may contribute to emergence of antimicrobial-resistant strains. The objective of this study was to detect the presence of extended-spectrum beta-lactamase- (ESBL ) producing Escherichia coli in poultry in Zambia. A total of 384 poultry samples were collected and analyzed for ESBL-producing Escherichia coli. The cultured E. coli isolates were subjected to antimicrobial susceptibility tests and the polymerase chain reaction for detection of bla CTX-M, bla SHV, and bla TEM genes. Overall 20.1%, 77/384, (95% CI; 43.2-65.5%) of total samples analyzed contained ESBL-producing Escherichia coli. The antimicrobial sensitivity test revealed that 85.7% (66/77; CI: 75.7-92) of ESBL-producing E. coli isolates conferred resistance to beta-lactam and other antimicrobial agents. These results indicate that poultry is a potential reservoir for ESBL-producing Escherichia coli. The presence of ESBL-producing Escherichia coli in poultry destined for human consumption requires strengthening of the antibiotic administering policy. This is important as antibiotic administration in food animals is gaining momentum for improved animal productivity in developing countries such as Zambia. PMID- 27190520 TI - The Reliability of Pharyngeal High Resolution Manometry with Impedance for Derivation of Measures of Swallowing Function in Healthy Volunteers. AB - Purpose. We evaluated the intra- and interrater agreement and test-retest reliability of analyst derivation of swallow function variables based on repeated high resolution manometry with impedance measurements. Methods. Five subjects swallowed 10 * 10 mL saline on two occasions one week apart producing a database of 100 swallows. Swallows were repeat-analysed by six observers using software. Swallow variables were indicative of contractility, intrabolus pressure, and flow timing. Results. The average intraclass correlation coefficients (ICC) for intra- and interrater comparisons of all variable means showed substantial to excellent agreement (intrarater ICC 0.85-1.00; mean interrater ICC 0.77-1.00). Test-retest results were less reliable. ICC for test-retest comparisons ranged from slight to excellent depending on the class of variable. Contractility variables differed most in terms of test-retest reliability. Amongst contractility variables, UES basal pressure showed excellent test-retest agreement (mean ICC 0.94), measures of UES postrelaxation contractile pressure showed moderate to substantial test retest agreement (mean Interrater ICC 0.47-0.67), and test-retest agreement of pharyngeal contractile pressure ranged from slight to substantial (mean Interrater ICC 0.15-0.61). Conclusions. Test-retest reliability of HRIM measures depends on the class of variable. Measures of bolus distension pressure and flow timing appear to be more test-retest reliable than measures of contractility. PMID- 27190519 TI - Strains, Mechanism, and Perspective: Salmonella-Based Cancer Therapy. AB - Recently, investigation of bacterial-based tumor therapy has regained focus due to progress in molecular, cellular, and microbial biology. Many bacteria such as Salmonella, Listeria, Escherichia, and Clostridium have proved to have tumor targeting and in some cases even tumor-destroying phenotypes. Furthermore, bacterial clinical treatments for cancer have been improved by combination with other therapeutic methods such as chemotherapeutic drugs and radioactive agents. Synthetic biology techniques have also driven the development of new bacterial based cancer therapies. However, basic questions about the mechanisms of bacterial-mediated tumor targeting and destruction are still being elucidated. In this review, we focus on three tumor-therapeutic Salmonella models, the most intensively studied bacterial genus in this field. One of these Salmonella models is our Salmonella enterica serovar Typhimurium LT2 derived strain CRC2631, engineered to minimize toxicity but maximize tumor-targeting and destruction effects. The other two are VNP20009 and A1-R. We compare the means by which these therapeutic candidate strain models were selected for study, their tumor targeting and tumor destruction phenotypes in vitro and in vivo, and what is currently known about the mechanisms by which they target and destroy tumors. PMID- 27190521 TI - Large D-Dimer Fluctuation in Normal Pregnancy: A Longitudinal Cohort Study of 4,117 Samples from 714 Healthy Danish Women. AB - Introduction. D-dimer levels increase throughout pregnancy, hampering the usefulness of the conventional threshold for dismissing thromboembolism. This study investigates the biological fluctuation of D-dimer in normal pregnancy. Methods. A total of 801 healthy women with expected normal pregnancies were recruited. D-dimer was repeatedly measured during pregnancy, at active labor, and on the first and second postpartum days. Percentiles for each gestational week were calculated. Each individual D-dimer was normalized by transformation into percentiles for the relevant gestational age or delivery group. The range in percentage points during the pregnancy and the delivery was calculated, and reference intervals were calculated for each pregnancy trimester, during vaginal delivery and scheduled and emergency cesarean section, and for the first and second day postpartum. Results. D-dimer increased during pregnancy; the maximal fluctuation was approximately 20 percentile points in approximately half of the women. In one out of ten women, the D-dimer values fluctuated by more than 50 percentile points. Conclusions. Due to the biological variation in D-dimer within each individual woman during normal pregnancy, repeated D-dimer measurements are of no clinical use in the evaluation of thromboembolic events during pregnancy. PMID- 27190522 TI - Clinicopathological Significance of Vimentin and Cytokeratin Protein in the Genesis of Squamous Cell Carcinoma of Cervix. AB - Cervical cancer is one of the commonest types of cancers worldwide especially in developing countries. Intermediate filaments protein family has shown a role in the diagnosis of various cancers, but a few studies are available about the vimentin and cytokeratin roles in the cervical cancer. This case control study aimed to interpret the expression of vimentin and cytokeratin proteins in the development and progression of cervical cancer and its correlation with clinicopathological features. The cytoplasmic expression of vimentin was observed in 40% of cases, but not in inflammatory lesions of cervix. It was noticed that vimentin expression was increasing significantly with high grade of the tumour. Cytokeratin expression was observed in 48.33% and it was noticed that the expression was 62.5% in well differentiated (G1), 45% in moderately differentiated (G2), and 41.66% in poorly differentiated carcinoma, yet statistically insignificant. The expression of vimentin and cytokeratin proteins was not significantly associated with age groups. The current findings concluded a possible role of vimentin in the development and progression of cervical cancer and vimentin marker will be useful in the diagnosis and grading of cervical cancer. PMID- 27190523 TI - Multilayer Membranes of Glycosaminoglycans and Collagen I Biomaterials Modulate the Function and Microvesicle Release of Endothelial Progenitor Cells. AB - Multilayer composite membrane of biomaterials can increase the function of adipose stem cells or osteoprogenitor cells. Recent evidence indicates endothelial progenitor cells (EPCs) and EPCs released microvesicles (MVs) play important roles in angiogenesis and vascular repair. Here, we investigated the effects of biomaterial multilayer membranes of hyaluronic acid (HA) or chondroitin sulfate (CS) and Collagen I (Col I) on the functions and MVs release of EPCs. Layer-by-layer (LBL) technology was applied to construct the multilayer composite membranes. Four types of the membranes constructed by adsorbing either HA or CS and Col I alternatively with different top layers were studied. The results showed that all four types of multilayer composite membranes could promote EPCs proliferation and migration and inhibit cell senility, apoptosis, and the expression of activated caspase-3. Interestingly, these biomaterials increased the release and the miR-126 level of EPCs-MVs. Moreover, the CS-Col I membrane with CS on the top layer showed the most effects on promoting EPCs proliferation, EPCs-MV release, and miR-126 level in EPCs-MVs. In conclusion, HA/CS and Collagen I composed multilayer composite membranes can promote EPCs functions and release of miR-126 riched EPCs-MVs, which provides a novel strategy for tissue repair treatment. PMID- 27190524 TI - Lymphoid Tissue Mesenchymal Stromal Cells in Development and Tissue Remodeling. AB - Secondary lymphoid organs (SLOs) are sites that facilitate cell-cell interactions required for generating adaptive immune responses. Nonhematopoietic mesenchymal stromal cells have been shown to play a critical role in SLO function, organization, and tissue homeostasis. The stromal microenvironment undergoes profound remodeling to support immune responses. However, chronic inflammatory conditions can promote uncontrolled stromal cell activation and aberrant tissue remodeling including fibrosis, thus leading to tissue damage. Despite recent advancements, the origin and role of mesenchymal stromal cells involved in SLO development and remodeling remain unclear. PMID- 27190526 TI - The Effect of Exclusive Breastfeeding on Hospital Stay and Morbidity due to Various Diseases in Infants under 6 Months of Age: A Prospective Observational Study. AB - Background. Mother's milk is the best for the babies. Protective and preventive role of breast milk was evaluated in this study by assessing the relation of type of feeding and duration of hospital stay or morbidity. Methods. This prospective study was conducted in a tertiary care hospital and 232 infants in the age group of 14 weeks to 6 months formed the sample. There are two groups of infants, that is, one for breastfed and one for top fed infants. Statistical analysis was done and results were calculated up to 95% to 99% level of significance to find effect of feeding pattern on hospital stay due to various diseases and morbidity. Results. Prolonged hospital stay, that is, >7 days, was lesser in breastfed infants and results were statistically significant in case of gastroenteritis (p value < 0.001), bronchopneumonia (p value = 0.0012), bronchiolitis (p value = 0.005), otitis media (p value = 0.003), and skin diseases (p value = 0.047). Lesser morbidity was seen in breastfed infants with gastroenteritis (p value 0.0414), bronchopneumonia (p value 0.03705), bronchiolitis (p value 0.036706), meningitis (p value 0.043), and septicemia (p value 0.04). Conclusions. Breastfed infants have shorter hospital stay and lesser morbidity in regard to various diseases as compared to top fed infants. PMID- 27190525 TI - Magnitude of Neglected Tropical Diseases in Indonesia at Postmillennium Development Goals Era. AB - The world will enter the postmillennium development goals 2015 era. The achievements of the millennium development goals (MDGs) as a global development target need to be evaluated. A sustainable new reasonable target is important for neglected tropical diseases (NTD) elimination in Indonesia. This review describes the NTD situation in Indonesia and highlights problems beneath the NTD transmission. Multidisciplinary approach is a promising strategy to help the marginalized people. PMID- 27190527 TI - Anaphylaxis to IGIV in immunoglobulin-naive common variable immunodeficiency patient in the absence of IgG anti-IgA antibodies: successful administration of low IgA-containing immunoglobulin. AB - Although severe reactions to immunoglobulin preparations have been frequently reported, IgE antibodies against IgA are usually not investigated; and occur predominantly in previously sensitized patients. The purpose is to report anaphylaxis to IGIV during initial infusion in a patient with common variable immunodeficiency with absent IgA without prior sensitization and in the absence of detectable IgG anti-IgA antibodies, and positive skin tests for immediate hypersensitivity to four different preparations of IGIV, one subcutaneous immunoglobulin preparation, and to purified IgA. Patient was treated without side effects with IGIV preparation depleted of IgA to which immediate hypersensitivity skin test was negative. This case demonstrates that patients with CVID with no IgA and without prior exposure to immunoglobulin or plasma may develop anaphylaxis following initial infusion of IGIV, which appears to be due to IgE anti-IgA, and independent of IgG anti-IgA antibodies. Since there is no good correlation between anaphylaxis/anaphylactic reactions and IgG anti-IgA antibodies, and IgE anti-IgA antibody test is commercially unavailable, we suggest that the patients with CVID with absence of IgA might be skin tested for immediate hypersensitivity prior to initiation of immunoglobulin administration. However, such recommendation may require studies on a large number of patients with CVID with no detectable IgA. PMID- 27190528 TI - Methanolic Extract of Clinacanthus nutans Exerts Antinociceptive Activity via the Opioid/Nitric Oxide-Mediated, but cGMP-Independent, Pathways. AB - The objectives of the present study were to determine the mechanisms of antinociceptive effect of methanol extract of Clinacanthus nutans (Acanthaceae) leaves (MECN) using various animal nociceptive models. The antinociceptive activity of orally administered 10% DMSO, 100 mg/kg acetylsalicylic acid (ASA), 5 mg/kg morphine, or MECN (100, 250, and 500 mg/kg) was determined using the acetic acid-induced abdominal constriction (ACT), formalin-induced paw licking (FT), and hot plate tests (HPT). The role of opioid and nitric oxide/cyclic guanosine monophosphate (NO/cGMP) systems was also investigated. The results showed that MECN produced a significant (p < 0.05) antinociceptive response in all nociceptive models with the recorded ED50 value of 279.3 mg/kg for the ACT, while, for the early and late phases of the FT, the value was >500 mg/kg or 227.7 mg/kg, respectively. This antinociceptive activity was fully antagonized by naloxone (a nonselective opioid antagonist) but was partially reversed by l arginine (l-arg; a nitric oxide [NO] precursor), Nomega-nitro-l-arginine methyl ester hydrochloride (l-NAME; an NO synthase inhibitor), or their combinations thereof. In contrast, 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ; a soluble guanylyl cyclase inhibitor) enhanced the extract's antinociception. UHPLC analysis revealed the presence of several flavonoid-based compounds with antinociceptive action. In conclusion, MECN exerted the peripherally and centrally mediated antinociceptive activity via the modulation of the opioid/NO mediated, but cGMP-independent, systems. PMID- 27190530 TI - Evaluation of Medicinal Categorization of Atractylodes japonica Koidz. by Using Internal Transcribed Spacer Sequencing Analysis and HPLC Fingerprinting Combined with Statistical Tools. AB - Atractylodes rhizomes have been used as the herbal medicine "Changchul" or "Baekchul," according to their clinical purpose, in Korea, China, and Japan. Among the Atractylodes species, the medicinal use of Atractylodes japonica has been controversial, as it is categorized as both Changchul and Baekchul in those countries, and, moreover, parts of the rhizome have been differently used, depending on age of the plant, in Korea. Chromatographic fingerprinting by using HPLC combined with chemometric analyses and internal transcribed spacer (ITS) sequencing analysis were conducted to classify and identify 34 crude drugs derived from Atractylodes rhizomes. The identification of the samples, authenticated by their morphological features as A. japonica Koidz. (Changchul and Baekchul), A. chinensis Koidz., and A. macrocephala Koidz., was confirmed as A. japonica, A. chinensis, and A. macrocephala by ITS sequencing. The results from chemometric analyses showed that the chemical components of the crude drugs from A. japonica were significantly different from those from A. macrocephala but were similar to those from A. chinensis. The analyses also suggested that the categorization by age of A. japonica as Changchul or Baekchul is not recommended. The results indicate that A. japonica should be categorized as "Changchul" and should not be further categorized by age. PMID- 27190529 TI - Benefits of Whole-Body Vibration, as a Component of the Pulmonary Rehabilitation, in Patients with Chronic Obstructive Pulmonary Disease: A Narrative Review with a Suitable Approach. AB - Background. Appropriate management, including pulmonary rehabilitation, associated with correct diagnosis of chronic obstructive pulmonary disease (COPD) in patients can contribute to improving clinical conditions of these patients. Physical activity is recommended for COPD patients. Whole-body vibration (WBV) is a modality of physical activity. Putting together the biological effects and safe use of WBV, it may be a potentially feasible intervention to add to pulmonary rehabilitation. The purpose of this investigation was to systematically review studies regarding the effects of WBV, as a component of the pulmonary rehabilitation, in patients with COPD. Results. A total of six publications met inclusion for review. There was evidence to support the beneficial use of WBV to improve functional performance of the lower limbs and quality of life. However, the appropriateness of and descriptors of WBV methods were poorly described. Conclusions. The results of this review support the use of WBV as a component of pulmonary rehabilitation to assist management of patients with COPD. However, future research should examine the dose-response curve and optimal dosing regimen of WBV according to standard reporting recommendations for people with COPD. Such an approach will allow comparison among studies and the potential of meta analysis of randomized controlled trials. PMID- 27190532 TI - Clinical Experiences of Korean Medicine Treatment against Urinary Bladder Cancer in General Practice. AB - Urinary bladder cancer (UBC) is one of the most common cancers, with 1 out of every 26 men and 1 out of every 80 women worldwide developing the disease during their lifetime. Moreover, it is a disease that predominantly affects the elderly and is becoming a major health problem as the elderly population continues to rapidly increase. In spite of the rapid development of medical science, the 5 year survival rate has remained around 75% since the 1990s, and the FDA has approved no new drugs for UBC over the last 10 years. In addition, most patients experience frequent recurrence and poor quality of life after diagnosis. Therefore, in order to solve unmet needs by alternative methods, we present our clinical cases of UBC where we observed outstanding results including regression and recurrence prevention exclusively through Traditional Korean Medicine such as (1) herbal therapy, (2) acupuncture, (3) pharmacopuncture and needle-embedding therapy, (4) moxibustion, and (5) cupping therapy. From our experience, it appears that multimodal strategies for synergistic efficiency are more effective than single Korean Medicine treatment. We hope this will encourage investigation of the efficacy of Korean Medicine treatment in clinical trials for UBC patients. PMID- 27190533 TI - Endogenous L-Carnosine Level in Diabetes Rat Cardiac Muscle. AB - A novel method for quantitation of cardiac muscle carnosine levels using HPLC-UV is described. In this simple and reliable method, carnosine from the rat cardiac muscle and the internal standard, thymopentin, were extracted by protein precipitation with acetonitrile. The method was linear up to 60.96 MUg.mL(-1) for L-carnosine. The calibration curve was linear in concentration ranges from 0.5 to 60.96 MUg.mL(-1). The relative standard deviations obtained for intra- and interday precision were lower than 12% and the recoveries were higher than 90% for both carnosine and internal standard. We successfully applied this method to the analysis of endogenous carnosine in cardiac muscle of the diabetes rats and healthy control rats. The concentration of carnosine was significantly lower in the diabetes rats group, compared to that in the healthy control rats. These results support the usefulness of this method as a means of quantitating carnosine and illustrate the important role of L-carnosine in cardiac muscle. PMID- 27190531 TI - Chinese Herbal Medicine as Adjunctive Therapy to Chemotherapy for Breast Cancer: A Systematic Review and Meta-Analysis. AB - Chinese herbal medicine (CHM) has been increasingly employed during therapy for breast cancer, but its efficacy remains a matter of debate. This systematic review examined randomized controlled trials to provide a critical evaluation of this treatment. The results demonstrated that the combined use of CHM with chemotherapy may improve the immediate tumor response and reduce chemotherapy associated adverse events. Our findings highlight the poor quality of Chinese studies, and additional well-designed randomized controlled trials addressing the role of CHM are warranted. The lack of molecular-based evidence for CHM and Zheng has resulted in a limited understanding and acceptance of CHM and traditional Chinese medicine in Western countries. We believe that researchers should immediately explore a CHM-based cure, and CHM should be applied to routine care as soon as conclusive data are available. PMID- 27190534 TI - The Common Prescription Patterns Based on the Hierarchical Clustering of Herb Pairs Efficacies. AB - Prescription patterns are rules or regularities used to generate, recognize, or judge a prescription. Most of existing studies focused on the specific prescription patterns for diverse diseases or syndromes, while little attention was paid to the common patterns, which reflect the global view of the regularities of prescriptions. In this paper, we designed a method CPPM to find the common prescription patterns. The CPPM is based on the hierarchical clustering of herb-pair efficacies (HPEs). Firstly, HPEs were hierarchically clustered; secondly, the individual herbs are labeled by the HPEC (the clusters of HPEs); and then the prescription patterns were extracted from the combinations of HPEC; finally the common patterns are recognized statistically. The results showed that HPEs have hierarchical clustering structure. When the clustering level is 2 and the HPEs were classified into two clusters, the common prescription patterns are obvious. Among 332 candidate prescriptions, 319 prescriptions follow the common patterns. The description of the patterns is that if a prescription contains the herbs of the cluster (C 1), it is very likely to have other herbs of another cluster (C 2); while a prescription has the herbs of C 2, it may have no herbs of C 1. Finally, we discussed that the common patterns are mathematically coincident with the Blood-Qi theory. PMID- 27190535 TI - Characterization of the Physiological Response following In Vivo Administration of Astragalus membranaceus. AB - The botanical, Astragalus membranaceus, is a therapeutic in traditional Chinese medicine. Limited literature exists on the overall in vivo effects of A. membranaceus on the human body. This study evaluates the physiological responses to A. membranaceus by measuring leukocyte, platelet, and cytokine responses as well as body temperature and blood pressure in healthy individuals after the in vivo administration of A. membranaceus. A dose-dependent increase in monocytes, neutrophils, and lymphocytes was measured 8-12 hours after administration and an increase in the number of circulating platelets was seen as early as 4 hours. A dynamic change in the levels of circulating cytokines was observed, especially in interferon-gamma and tumor necrosis factor-alpha, IL-13, IL-6, and soluble IL-2R. Subjective symptoms reported by participants were similar to those typically experienced in viral type immune responses and included fatigue, malaise, and headache. Systolic and diastolic blood pressure were reduced within 4 hours after administration, while body temperature mildly increased within 8 hours after administration. In general, all responses returned to baseline values by 24 hours. Collectively, these results support the role of A. membranaceus in priming for a potential immune response as well as its effect on blood flow and wound healing. PMID- 27190536 TI - Effects of Zusanli and Ashi Acupoint Electroacupuncture on Repair of Skeletal Muscle and Neuromuscular Junction in a Rabbit Gastrocnemius Contusion Model. AB - Objective. To explore the effects of electroacupuncture (EA) at ST36 (EA-ST36) and at Ashi acupoints (EA-Ashi) on skeletal muscle repair. Methods. Seventy-five rabbits were randomly divided into five groups: normal, contusion, EA-Ashi, EA ST36, and EA at Ashi acupoints and ST36 (EA-AS). EA (0.4 mA, 2 Hz, 15 min) was applied after an acute gastrocnemius contusion. The morphology of myofibers and neuromuscular junctions (NMJs) and expressions of growth differentiation factor-8 (GDF-8), acetylcholinesterase (AChE), Neuregulin 1 (NGR1), and muscle-specific kinase (MuSK) were assessed 7, 14, and 28 days after contusion. Results. Compared with that in contusion group, there was an increase in the following respective parameters in treatment groups: the number and diameter of myofibers, the mean staining area, and continuities of NMJs. A comparison of EA-Ashi and EA-ST36 groups indicated that average myofiber diameter, mean staining area of NMJs, and expressions of AChE and NRG1 were higher in EA-Ashi group, whereas expression of GDF-8 decreased on day 7. However, increases in myofiber numbers, expressions of MuSK and AChE, as well as decreases in GDF-8 expression, and the discontinuities were observed in EA-ST36 group on the 28th day. Conclusion. Both EA-ST36 and EA Ashi promoted myofiber regeneration and restoration of NMJs. EA-Ashi was more effective at earlier stages, whereas EA-ST36 played a more important role at later stages. PMID- 27190537 TI - Synergism of Chinese Herbal Medicine: Illustrated by Danshen Compound. AB - The primary therapeutic effects of Chinese herbal medicine (CHM) are based on the properties of each herb and the strategic combination of herbs in formulae. The herbal formulae are constructed according to Chinese medicine theory: the "Traditional Principles for Constructing Chinese Herbal Medicinal Formulae" and the "Principles of Combining Medicinal Substances." These principles of formulation detail how and why multiple medicinal herbs with different properties are combined together into a single formula. However, the concept of herbal synergism in CHM still remains a mystery due to lack of scientific data and modern assessment methods. The Compound Danshen Formula (CDF) is a validated formula that has been used to treat a variety of diseases for hundreds of years in China and other countries. The CDF will be employed to illustrate the theory and principle of Chinese herbal medicine formulation. The aim of this review is to describe how Chinese herbal medicinal formulae are constructed according to Chinese medicine theory and to illustrate with scientific evidence how Chinese herbs work synergistically within a formula, thereby supporting Chinese medicine theory and practice. PMID- 27190538 TI - Ex Vivo Stromal Cell-Derived Factor 1-Mediated Differentiation of Mouse Bone Marrow Mesenchymal Stem Cells into Hepatocytes Is Enhanced by Chinese Medicine Yiguanjian Drug-Containing Serum. AB - Yiguanjian is administered in traditional Chinese medicine for liver diseases and has been demonstrated to reduce liver fibrosis. This study investigated the effect of Yiguanjian drug-containing serum (YGJ) with Stromal Cell-Derived Factor 1 (SDF-1) and Hepatocyte Growth Factor (HGF) on the differentiation of murine bone-marrow-derived mesenchymal cells (BM-MSCs) into hepatocytes in vitro. Adherent MSCs were isolated from murine bone marrow. Differentiation was induced by 20 ng/mL HGF, 50 ng/mL SDF-1, and 20% Yiguanjian drug-containing serum for 7 to 28 days, and mature hepatocytes' marker albumin (ALB) and cholangiocytes' marker cytokeratin-18 (CK-18) were assessed by immunocytochemistry and western blot. BM-MSCs exhibited homogeneous spindle shape growth after subculture and stained positive for CD90 and negative for CD34. After induction with HGF + normal serum or YGJ for 14 days, HGF + SDF-1 + normal serum for 7 days, or HGF + SDF-1 + YGJ for 5 days, MSCs' morphology changed gradually and begun to resemble hepatocyte-like cells. Cultures supplemented with HGF + SDF-1 + YGJ contained significantly higher proportions of ALB and CK-18 positive cells than cultures supplemented with HGF + SDF-1 + normal serum at day 7. These observations corroborated the results of western blot. In conclusion, Yiguanjian drug containing serum could facilitate the differentiation of murine BM-MSCs into hepatocytes in vitro and has a synergistic effect with SDF-1 and HGF. PMID- 27190540 TI - Composition Analysis and Inhibitory Effect of Sterculia lychnophora against Biofilm Formation by Streptococcus mutans. AB - Pangdahai is a traditional Chinese drug, specifically described in the Chinese Pharmacopoeia as the seeds of Sterculia lychnophora Hance. Here, we separated S. lychnophora husk and kernel, analyzed the nutrient contents, and investigated the inhibitory effects of S. lychnophora ethanol extracts on cariogenic properties of Streptococcus mutans, important bacteria in dental caries and plaque formation. Ethanol extracts of S. lychnophora showed dose-dependent antibacterial activity against S. mutans with significant inhibition at concentrations higher than 0.01 mg/mL compared with the control group (p < 0.05). Furthermore, biofilm formation was decreased by S. lychnophora at concentrations > 0.03 mg/mL, while bacterial viability was decreased dose-dependently at high concentrations (0.04, 0.08, 0.16, and 0.32 mg/mL). Preliminary phytochemical analysis of the ethanol extract revealed a strong presence of alkaloid, phenolics, glycosides, and peptides while the presence of steroids, terpenoids, flavonoids, and organic acids was low. The S. lychnophora husk had higher moisture and ash content than the kernel, while the protein and fat content of the husk were lower (p < 0.05) than those of the kernel. These results indicate that S. lychnophora may have antibacterial effects against S. mutans, which are likely related to the alkaloid, phenolics, glycosides, and peptides, the major components of S. lychnophora. PMID- 27190541 TI - The Effects of Xiangqing Anodyne Spray on Treating Acute Soft-Tissue Injury Mainly Depend on Suppressing Activations of AKT and p38 Pathways. AB - Objectives. In the present study we try to elucidate the mechanism of Xiangqing anodyne spray (XQAS) effects on acute soft-tissue injury (STI). Methods. Acute STI model was established by hammer blow in the rat hind leg muscle. Within 8 hours, instantly after modeling and per 2-hour interval repeated topical applications with or without XQAS, CP or IH ethanol extracts spray (CPS and IHS) were performed, respectively; muscle swelling rate and inflammation-related biochemical parameters, muscle histological observation, and mRNA and protein expression were then examined. Results. XQAS dose-dependently suppressed STI caused muscle swelling, proinflammatory mediator productions, and oxidative stress as well as severe pathological changes in the injured muscle tissue. Moreover, CPS mainly by blocking p38 activation while IHS majorly by blocking AKT activation led to cytoplastic IkappaBalpha degradation with NF-kappaB p65 translocated into the nucleus. There are synergistic effects between CP and IH components in the XQAS on preventing from acute STI with suppressing IkappaBalpha degradation, NF-kappaB p65 translocation, and subsequent inflammation and oxidative stress-related abnormality. Conclusion. Marked effects of XQAS on treating acute STI are ascribed to strong anti-inflammatory and antioxidative actions with a reasonable combination of CP active components, blocking p38-NF kappaB pathway activated, and IH active components, blocking AKT-NF-kappaB pathway activated. PMID- 27190542 TI - Acupuncture for Chronic Urinary Retention due to Spinal Cord Injury: A Systematic Review. AB - No systematic review has been published on the use of acupuncture for the treatment of chronic urinary retention (CUR) due to spinal cord injury (SCI). The aim of this review was to assess the effectiveness and safety of acupuncture for CUR due to SCI. Three randomized controlled trials (RCTs) including 334 patients with CUR due to SCI were included. Meta-analysis showed that acupuncture plus rehabilitation training was much better than rehabilitation training alone in decreasing postvoid residual (PVR) urine volume (MD -109.44, 95% CI -156.53 to 62.35). Likewise, a combination of acupuncture and aseptic intermittent catheterization was better than aseptic intermittent catheterization alone in improving response rates (RR 1.23, 95% CI 1.10 to 1.38). No severe adverse events were reported. In conclusion, acupuncture as a complementary therapy may have a potential effect in CUR due to SCI in decreasing PVR and improving bladder voiding. Additionally, acupuncture may be safe in treating CUR caused by SCI. However, due to the lack of high quality RCTs, we could not draw any definitive conclusions. More well-designed RCTs are needed to provide strong evidence. PMID- 27190543 TI - Chemical Constituents from Daphne giraldii Nitsche and Their Contents Simultaneous Determination by HPLC. AB - Daphne giraldii Nitsche (Thymelaeaceae) is widely distributed in the Chinese provinces of Shaanxi, Gansu, and Qinghai, which has been used in Chinese folk medicine to treat ache and rheumatism. Pharmacologic tests have revealed that the plant has anti-inflammatory, analgesic, and anticancer activities. However, there is still not enough systemic investigation on the chemical constituents and the method for the contents simultaneous determination in D. giraldii. Therefore, the isolation and characterization of the compounds from the stem barks of this plant were reported. Moreover, a facile, accurate, and reliable method has been developed and validated for their simultaneous determination using HPLC-DAD. PMID- 27190539 TI - The Relieving Effects of BrainPower Advanced, a Dietary Supplement, in Older Adults with Subjective Memory Complaints: A Randomized, Double-Blind, Placebo Controlled Trial. AB - Subjective memory complaints (SMCs) are common in older adults that can often predict further cognitive impairment. No proven effective agents are available for SMCs. The effect of BrainPower Advanced, a dietary supplement consisting of herbal extracts, nutrients, and vitamins, was evaluated in 98 volunteers with SMCs, averaging 67 years of age (47-88), in a randomized, double-blind, placebo controlled trial. Subjective hypomnesis/memory loss (SML) and attention/concentration deficits (SAD) were evaluated before and after 12-week supplementation of BrainPower Advanced capsules (n = 47) or placebo (n = 51), using a 5-point memory questionnaire (1 = no/slight, 5 = severe). Objective memory function was evaluated using 3 subtests of visual/audio memory, abstraction, and memory recall that gave a combined total score. The BrainPower Advanced group had more cases of severe SML (severity ? 3) (44/47) and severe SAD (43/47) than the placebo group (39/51 and 37/51, < 0.05, < 0.05, resp.) before the treatment. BrainPower Advanced intervention, however, improved a greater proportion of the severe SML (29.5%)(13/44) (P < 0.01) and SAD (34.9%)(15/43)(P < 0.01) than placebo (5.1% (2/39) and 13.5% (5/37), resp.). Thus, 3-month BrainPower Advanced supplementation appears to be beneficial to older adults with SMCs. PMID- 27190544 TI - Prevalence of HIV and hepatitis B coinfection in Ghana: a systematic review and meta-analysis. AB - BACKGROUND: Human immunodeficiency virus (HIV) and hepatitis B virus (HBV) coinfection has been associated with higher morbidity and mortality and may impact significantly on healthcare resource utilization. However, in Ghana, accurate estimates of the prevalence of HIV/HBV coinfection needed to inform policy decisions and the design of public health interventions are currently lacking. In this study, our aim was to determine the HIV/HBV coinfection prevalence rate in Ghana. METHODS: Primary studies reporting prevalence of HIV/HBV coinfection in Ghana were retrieved through searches conducted in PubMed, science direct, Google scholar and Africa journals online (AJOL) databases. The websites of the Ministry of Health and Ghana Health Service were also searched for related reports or reviews. Additionally, the online repository of two leading Ghanaian universities were searched to identify unpublished thesis related to the subject. All online searches were conducted between 01/03/2016 and 12/03/2016. Further searches were conducted through reference screening of retrieved papers. RESULTS: Twelve (12) studies published between 1999 and 2016 and conducted across seven (7) regions of Ghana were included in this review. The three (3) regions with no studies' representation were Upper East, Upper West and Central regions. The 12 included studies involved a total of 8162 HIV patients. The reported HIV/HBV coinfection prevalence rates ranged from 2.4 to 41.7 %. The pooled HIV/HBV coinfection prevalence rate was determined as 13.6 % (95 % CI 10.2 16.8 %; P < 0.001). CONCLUSIONS: In Ghana, about one in seven HIV patients may be also be chronically infected with HBV. Preventive interventions and strategic policy directions including systematic screening of all newly diagnosed HIV cases for coinfection will be needed, so as to improve management strategies for HBV infection and antiretroviral therapy (ART) implementation. PMID- 27190545 TI - Human serum prebeta1-high density lipoprotein levels are independently and negatively associated with coronary artery diseases. AB - BACKGROUND: Serum prebeta1-high density lipoprotein (prebeta1-HDL) was defined by two-dimensional non-denaturing linear gel electrophoresis and apolipoprotein A-I immuno-blotting. Serum prebeta1-HDL seems to play an important role in reverse cholesterol transport, a well-known anti-atherosclerosis process. However, there are still debatable questions for its quantification and coronary artery disease (CAD) relevance. METHODS: We isolated the prebeta1-HDL using a new native polyacrylamide gel electrophoresis (PAGE) system and lipid pre-staining serum. We established a two-demensional gel electrophoresis system. RESULTS: We measured the prebeta1-HDL in Tangier disease patients and subjects with cholesterol ester transfer protein (CETP) mutation. The prebeta1-HDL is clearly separated from lipid-free apoA-I monomer and cannot be converted into other HDL particles under lecithin-cholesterol acyltransferase (LCAT) inhibition. This prebeta1-HDL is a spheroidal particle with the highest apoA-1/cholesterol ratio and highest density (>=1.21 g/ml), as compared with all other HDLs. Importantly, we found that serum from subjects with Tangier disease or with cholesterol ester transfer protein (CETP) mutation have no detectible prebeta1-HDL particles. We recruited a total of 102 subjects underwent diagnostic coronary angiography and measured their prebeta1-HDL levels. Among them, 56 had no stenosis of coronary artery and 46 were diagnosed as CAD, which was predefined as the presence of a luminal diameter stenosis >=50 % in at least 1 major coronary artery territory. We found that prebeta1-HDL is independently and negatively associated with the severity of the coronary artery stenosis (Gensini score). CONCLUSION: We established a novel and simple method for human serum prebeta1-HDL quantification. We found that human lower prebeta1-HDL is an independent predictor for severer coronary artery stenosis. PMID- 27190546 TI - Knowledge, attitudes and determinants of exclusive breastfeeding practice among Ghanaian rural lactating mothers. AB - BACKGROUND: The practice of exclusive breastfeeding (EBF) is influenced by maternal knowledge and attitudes as well as socio-demographic and cultural factors. This study assessed knowledge, attitudes and practice of EBF among rural lactating mothers with infants aged 0-6 months. Factors associated to the practice of EBF were also investigated. METHODS: This cross-sectional study was conducted among 190 rural lactating mothers with infants aged 0-6 months seeking postnatal care at a health centre in Ghana. All data was collected using a questionnaire that contained both closed and open ended questions. RESULTS: About 26 % (n = 50) of the mothers were unable to correctly define EBF. The majority (92.6 %, n = 176) of the mothers said they felt good to EBF for 6 months, to breastfed on demand (99.5 %, n = 189) and did not have difficulties EBF (90 %, n = 171). Despite the generally positive attitude towards EBF, 42 % (n = 79) of the mothers did not EBF their babies. These mothers did not practice EBF because they misunderstood certain signs of the child to mean wanting to eat food or drink water, regarded breastmilk to be inadequate to meet the nutritional needs of the child and misunderstood healthcare professionals' EBF advice. Higher maternal education was associated with higher likelihood of EBF (OR 3.5; 95 % CI 1.6, 7.7; p = 0.002). Mothers whose babies were younger than 3 months were more likely to EBF (OR 12.0; 95 % CI 4.4, 32.5; p < 0.001) than those having babies aged >= 3 months. Furthermore, higher knowledge of EBF was associated with the likelihood of EBF (OR 5.9; 95 % CI 2.6, 13.3; p < 0.001). CONCLUSION: Mothers' knowledge and attitudes towards EBF were favourable but practice of EBF was suboptimal. This study adds additional evidence that knowledge of EBF, child's age and maternal level of education are important determinants of the practice of EBF. Beyond dissemination of health messages, healthcare professionals should pay more counselling attention to less educated mothers, and also older children's caregivers. PMID- 27190547 TI - Factors associated with prelacteal feeding in North Eastern Ethiopia: A community based cross-sectional study. AB - BACKGROUND: In spite of the negative impact of prelacteal feeding on the growth and development of children, it is widely practiced in Ethiopia. This study aimed to assess prelacteal feeding practices and associated factors among mothers of children aged less than 24 months in the North Wello zone. METHODS: A quantitative community based cross-sectional study was employed during March 2015. Eight hundred and forty four (844) mother-child pairs were selected by multi-stage sampling technique. Data were collected by face-to-face interview. Descriptive statistics, binary and multiple logistic regression analyses were employed to identify factors associated with prelacteal feeding practice. Variables with a p-value <0.05 were identified as statistically significant factors. RESULTS: The prevalence of prelacteal feeding was 11.1 % (95 % confidence interval [CI]: 9.0, 13.0). Colostrum discarding (adjusted odds ratio [AOR]: 8.7; 95 % CI (3.8, 20.1)) and lack of counseling about breastfeeding (AOR: 2.6; 95 % CI 1.27, 5.4) were the factors associated with prelacteal feeding. The major reasons stated for providing prelacteal feeds were "culture" and "do not have enough milk". CONCLUSION: Prelacteal feeds are offered to nearly one child in every ten in the North Wello zone. Colostrum removal and lack of counseling on breastfeeding at antenatal care visit are important positive predictors of prelacteal feeding practice. Awareness of the risks associated with prelacteal feeding, promotion of counseling on breastfeeding and the health benefit of colostrum during antenatal care visits are recommended interventions to reduce prelacteal feeding practices in the study areas. PMID- 27190548 TI - Mathematical Model of Three Age-Structured Transmission Dynamics of Chikungunya Virus. AB - We developed a new age-structured deterministic model for the transmission dynamics of chikungunya virus. The model is analyzed to gain insights into the qualitative features of its associated equilibria. Some of the theoretical and epidemiological findings indicate that the stable disease-free equilibrium is globally asymptotically stable when the associated reproduction number is less than unity. Furthermore, the model undergoes, in the presence of disease induced mortality, the phenomenon of backward bifurcation, where the stable disease-free equilibrium of the model coexists with a stable endemic equilibrium when the associated reproduction number is less than unity. Further analysis of the model indicates that the qualitative dynamics of the model are not altered by the inclusion of age structure. This is further emphasized by the sensitivity analysis results, which shows that the dominant parameters of the model are not altered by the inclusion of age structure. However, the numerical simulations show the flaw of the exclusion of age in the transmission dynamics of chikungunya with regard to control implementations. The exclusion of age structure fails to show the age distribution needed for an effective age based control strategy, leading to a one size fits all blanket control for the entire population. PMID- 27190549 TI - A Novel Automatic Rapid Diagnostic Test Reader Platform. AB - A novel automatic Rapid Diagnostic Test (RDT) reader platform is designed to analyze and diagnose target disease by using existing consumer cameras of a laptop-computer or a tablet. The RDT reader is useable with numerous lateral immunochromatographic assays and similar biomedical tests. The system has two different components, which are 3D-printed, low-cost, tiny, and compact stand and a decision program named RDT-AutoReader 2.0. The program takes the image of RDT, crops the region of interest (ROI), and extracts the features from the control end test lines to classify the results as invalid, positive, or negative. All related patient's personal information, image of ROI, and the e-report are digitally saved and transferred to the related clinician. Condition of the patient and the progress of the disease can be monitored by using the saved data. The reader platform has been tested by taking image from used cassette RDTs of rotavirus (RtV)/adenovirus (AdV) and lateral flow strip RDTs of Helicobacter pylori (H. pylori) before discarding them. The created RDT reader can also supply real-time statistics of various illnesses by using databases and Internet. This can help to inhibit propagation of contagious diseases and to increase readiness against epidemic diseases worldwide. PMID- 27190550 TI - Models and algorithms for genome rearrangement with positional constraints. AB - BACKGROUND: Traditionally, the merit of a rearrangement scenario between two gene orders has been measured based on a parsimony criteria alone; two scenarios with the same number of rearrangements are considered equally good. In this paper, we acknowledge that each rearrangement has a certain likelihood of occurring based on biological constraints, e.g. physical proximity of the DNA segments implicated or repetitive sequences. RESULTS: We propose optimization problems with the objective of maximizing overall likelihood, by weighting the rearrangements. We study a binary weight function suitable to the representation of sets of genome positions that are most likely to have swapped adjacencies. We give a polynomial time algorithm for the problem of finding a minimum weight double cut and join scenario among all minimum length scenarios. In the process we solve an optimization problem on colored noncrossing partitions, which is a generalization of the Maximum Independent Set problem on circle graphs. CONCLUSIONS: We introduce a model for weighting genome rearrangements and show that under simple yet reasonable conditions, a fundamental distance can be computed in polynomial time. This is achieved by solving a generalization of the Maximum Independent Set problem on circle graphs. Several variants of the problem are also mentioned. PMID- 27190551 TI - Acute appendicitis in overweight patients: the role of preoperative imaging. AB - BACKGROUND: The diagnosis of acute appendicitis in overweight patients is challenging due to the limited value of the clinical examination. The benefits of ultrasonography and abdominal CT have been studied in the general population, but there is limited data regarding their use in overweight and obese patients with suspected appendicitis. This study analyzes the role of preoperative radiological modalities in overweight patients with suspected appendicitis. METHODS: Retrospective analysis of a prospectively acquired database including 705 patients operated for suspected acute appendicitis. Patients were divided into two groups according to their BMI (BMI >=25 kg/m(2) (n = 242) and BMI <25 kg/m(2) (n = 463)). The use of preoperative radiological modalities, laboratory findings and outcome parameters were analyzed. RESULTS: Ultrasonography was the preferred radiological assessment in our cohort (68 % in BMI <25 kg/m and 52.4 % in BMI >=25 kg/m(2)). However, it was non-conclusive in 42 % of overweight as compared to 6 % in patients with a BMI < 25 (p < 0.0001). This difference was particularly obvious between female patients (8 % of non-conclusive US for BMI <25 kg/m(2) vs 52 % for BMI >=25 kg/m(2), p < 0.0001). Significantly more CT scans were performed in overweight patients (37 % vs. 20 %; p <0.0001). The accuracy of CT did not differ according to BMI (85 % vs. 88 %; p = 0.76). Preoperative radiological imaging did not significantly delay surgery. Laparoscopy was the preferred approach for both groups (98.2 % vs 98.7 %, P = 0.86) with an overall conversion rate of 4 %. The overall rate of negative appendectomy was 10 %. CONCLUSIONS: The role of ultrasonography in patients with BMI >=25 kg/m(2) with suspected acute appendicitis is questionable due to its high rate of non conclusive findings. Therefore, abdominal CT scans should be preferred to investigate suspected appendicitis in overweight patient if clinical findings are not conclusive. PMID- 27190552 TI - Pelvic alveolar rhabdomyosarcoma in a young adult. AB - Rhabdomyosarcomas are soft-tissue tumors, rare in adults. Accounting for nearly 5% of childhood cancers, they represent less than 0.03% of adult malignancies (1, 2). Three different subtypes of rhabdomyosarcoma have been described (embryonal, alveolar and pleomorphic), making up approximately 50%, 30%, and 20% of the cases, respectively (3). Although the definitive diagnosis is made pathologically, some distinguishing features among these subtypes, and between rhabdomyosarcomas and other soft-tissue tumors, can be suggested on MRI and CT. We present an interesting case of a 20-year-old female with a locally aggressive pelvic alveolar rhabdomyosarcoma. While the prognosis has improved with newer treatment techniques, overall survival rates remain poor. Our case study presents typical features of a rare disease, which can often present a diagnostic dilemma for clinicians. PMID- 27190554 TI - Primary sacrococcygeal chordoma with unusual skeletal muscle metastasis. AB - Chordomas are rare neoplasms that do not often metastasize. Of the small percent that do metastasize, they very infrequently involve skeletal muscle. Only a few cases of skeletal muscle metastases have been reported in the literature. We report an unusual case of a patient with a primary sacrococcygeal chordoma who experienced a long period of remission but who subsequently developed recurrence and multiple metastatic lesions to skeletal muscles including the deltoid, triceps, and pectineus. PMID- 27190553 TI - Bone metastasis on Tc99-m sestamibi myocardial perfusion scan. AB - A 75-year-old woman presented to our department for a stress myocardial perfusion imaging study with Tc99m-sestamibi. Incidental focal uptake, found in the left upper anterior chest, was initially felt to be located in the left breast. After additional single-photon CT imaging was performed the same day, extracardiac foci within the ribs, spine, and left lung (worrisome for active metastases) were shown to be present, with the initial focus located within a left rib rather than a breast. A review of previous radiographic and nuclear imaging studies confirmed metastatic disease from recurrent follicular thyroid cancer. Atypical focal extracardiac activity must be closely scrutinized for the possibility of malignancy, as Tc99m-sestamibi (in addition to being myocardium-avid) is tumor avid. PMID- 27190555 TI - Osteolytic mass bridging two cervical vertebrae: Unusual presentation of a vertebral body hemangioma. AB - Vertebral hemangioma is the most common spinal axis tumor. This rare presentation of a vertebral hemangioma extended contiguously from one cervical vertebra to another, encasing the vertebral artery, and thereby mimicking other tumors of the spine. We discuss the differential diagnosis of bridging vertebral masses. PMID- 27190556 TI - Epithelioid hemangioma of the spine: Two cases. AB - We report two cases of epithelioid hemangioma (EH) manifested in the thoracic spine with associated clinical, radiographic, and pathological findings. Epithelioid hemangioma is a benign vascular tumor that can involve any bone (including the spine in a subset of patients). Although recognized as a benign tumor by the WHO, it can display locally aggressive features. Within the spine, these features may lead to pain, instability, and/or neurologic dysfunction. The radiographic appearance is most typically that of a lytic, well-defined lesion on plain film or CT. The MRI appearance is typically hypointense on T1WI, hyperintense on T2WI, and avidly enhancing, often with an extraosseous soft tissue component. PMID- 27190557 TI - Transient global amnesia after cerebral angiography still occurs: Case report and literature review. AB - Transient global amnesia is considered a very rare complication of diagnostic cerebral angiography, and has been reported only in a limited number of case reports more than 15 years ago. We describe a patient experiencing transient global amnesia following cerebral digital subtraction angiography. While the condition by definition is self-limiting, its differential diagnoses may cause severe morbidity and/or mortality if left untreated. It is therefore important to build and maintain awareness of transient global amnesia as a possible complication of cerebral angiography. PMID- 27190558 TI - Two foci of FDG-avid secondary tumoral calcinosis incidentally noted in a patient with small-cell lung carcinoma after PET/CT. AB - This case report describes intense F-18 fluorodeoxyglucose (FDG) uptake within two foci of secondary tumoral calcinosis, incidentally noted during the workup of small-cell lung cancer. The patient had insulin-dependent diabetes mellitus and secondary hyperparathyroidism as a result of IgA nephropathy. PMID- 27190559 TI - A case of hyperfunctioning pancreatic mixed adenoneuroendocrine carcinoma (MANEC) arising from ectopic pancreatic tissue in the liver. AB - We report the case of a hyperfunctioning mixed adenoneuroendocrine carcinoma (MANEC) arising from ectopic pancreatic tissue in the liver. To our knowledge, the imaging appearance of a MANEC in the liver has never been reported. Literature on MANEC and its imaging features, including its appearance on the MR hepatobiliary phase and differential considerations, are reviewed and discussed. PMID- 27190560 TI - Combined laparoscopic placement of a PTBD demonstrating multidisciplinary problem solving in a complex patient. AB - In rare cases, biliary drainage is prevented by colonic position. When these situations arise within a critically ill patient who is not a good surgical candidate, unique solutions must be found. In this case, the solution was to use laparoscopic assistance to displace the colon while the interventional radiology team successfully accessed the biliary system. PMID- 27190561 TI - Colosplenopleural fistula: An unusual colonic fistula in a 44-year-old male with Crohn's disease. AB - A 44-year-old male with a history of well-controlled human immunodeficiency virus disease and Crohn's disease presented with fever, cough, and left-sided chest pain with radiation to his back. His medical history was notable for a medically managed spontaneous microperforation of the colon at the splenic flexure 30 months prior, and recurrent left-lower-lobe pneumonia with empyema and a splenic abscess within the past 24 months. CT demonstrated a complex left pleural fluid collection with fistulous connection through the spleen and into the large bowel. The patient tolerated a diverting loop ileostomy without complications and was discharged home with plans for resection of the fistulous tract and splenectomy in several months. PMID- 27190562 TI - Theoretical and experimental study of the porous film using quartz crystal microbalance. AB - The self-assembled multilayers have been studied by many researchers to modify the surfaces of artificial implants for increasing biocompatibility. The accurate mechanical properties of the film can only be obtained from the experimental results using appropriate theoretical models. As the film is composed of both solid polymers and fluid, this paper proposes a two-phase model. Based on the volume average method, the momentum equations are derived for both solid and liquid phases. In order to test our model, we built the porous film on the gold chip of the quartz crystal microbalance using the layer-by-layer method. The buildup process is based on the electrostatic interactions between anionic sodium hyaluronate and cationic chitosan by imitating the endothelial surface layer. By fitting our model to the experimental changes of the resonant frequency and dissipation factor, we get reasonable values of the film thickness, the porosity, the shear modulus of the solid phase, and the permeability. Compared with the existing models, the newly introduced permeability is an important property of the porous layer affecting the values of other parameters. Our model can provide more intrinsic properties of the self-assembled polymeric network and explain its interaction with the permeating fluid. PMID- 27190563 TI - Effects of shear on P-selectin deposition in microfluidic channels. AB - Traditional leukocyte adhesion assays have provided significant insight into the mechanisms of leukocyte rolling in part through the use of homogeneously coated surfaces. These assays typically involve protein coating of glass coverslips or plastic petri dishes applied via a static drop of protein solution. With this approach, it is difficult to spatially control the location of proteins to fabricate surface-bound protein gradients that mimic in vivo situations. Microfluidic patterning of proteins with microfluidic devices has become a popular technique due to the ability to spatially pattern proteins on a cellular scale. Despite the advantages of microfluidic patterning, few studies have systematically investigated the effects of perfusion time, protein concentration, and perfusion shear stress on protein deposition. Herein, we demonstrated the fabrication of both line and step gradients of P-selectin on glass substrates that support cell rolling and adhesion assays. Investigation of the flow conditions during the microfluidic patterning led to several significant findings. We observed that the protein deposition time of 5 min was sufficient to deposit adequate P-selectin to support neutrophil rolling. We demonstrated that the amount of membrane P-selectin (mP-selectin) or recombinant P-selectin (rP selectin) deposited showed a dependence on the perfusion shear stress between 4.0 and 32.0 dyn/cm(2), while similar studies with fibronectin or fibrinogen showed no shear stress dependence. Finally, we also created step changes in surface adherent protein concentration of P-selectin to characterize leukocyte-rolling behavior in response to sudden changes in ligand density. PMID- 27190566 TI - Characterization of enzymatic micromachining for construction of variable cross section microchannel topologies. AB - The ability to harness enzymatic activity as an etchant to precisely machine biodegradable substrates introduces new possibilities for microfabrication. This flow-based etching is straightforward to implement, enabling patterning of microchannels with topologies that incorporate variable depth along the cross sectional dimension. Additionally, unlike conventional small-molecule formulations, the macromolecular nature of enzymatic etchants enables features to be precisely positioned. Here, we introduce a kinetic model to characterize the enzymatic machining process and its localization by co-injection of a macromolecular inhibitor species. Our model captures the interaction between enzyme, inhibitor, and substrate under laminar flow, enabling rational prediction of etched microchannel profiles so that cross-sectional topologies incorporating complex lateral variations in depth can be constructed. We also apply this approach to achieve simultaneous widening of an entire network of microchannels produced in the biodegradable polymeric substrate poly(lactic acid), laying a foundation to construct systems incorporating a broad range of internal cross sectional dimensions by manipulating the process conditions. PMID- 27190564 TI - Advances in monoliths and related porous materials for microfluidics. AB - In recent years, the use of monolithic porous polymers has seen significant growth. These materials present a highly useful support for various analytical and biochemical applications. Since their introduction, various approaches have been introduced to produce monoliths in a broad range of materials. Simple preparation has enabled their easy implementation in microchannels, extending the range of applications where microfluidics can be successfully utilized. This review summarizes progress regarding monoliths and related porous materials in the field of microfluidics between 2010 and 2015. Recent developments in monolith preparation, solid-phase extraction, separations, and catalysis are critically discussed. Finally, a brief overview of the use of these porous materials for analysis of subcellular and larger structures is given. PMID- 27190567 TI - Multiphase ferrofluid flows for micro-particle focusing and separation. AB - Ferrofluids have demonstrated great potential for a variety of manipulations of diamagnetic (or non-magnetic) micro-particles/cells in microfluidics, including sorting, focusing, and enriching. By utilizing size dependent magnetophoresis velocity, most of the existing techniques employ single phase ferrofluids to push the particles towards the channel walls. In this work, we demonstrate a novel strategy for focusing and separating diamagnetic micro-particles by using the laminar fluid interface of two co-flowing fluids-a ferrofluid and a non-magnetic fluid. Next to the microfluidic channel, microscale magnets are fabricated to generate strong localized magnetic field gradients and forces. Due to the magnetic force, diamagnetic particles suspended in the ferrofluid phase migrate across the ferrofluid stream at the size-dependent velocities. Because of the low Reynolds number and high Peclet number associated with the flow, the fluid interface is sharp and stable. When the micro-particles migrate to the interface, they are accumulated near the interface, resulting in effective focusing and separation of particles. We investigated several factors that affect the focusing and separation efficiency, including susceptibility of the ferrofluid, distance between the microfluidic channel and microscale magnet, and width of the microfluidic channel. This concept can be extended to multiple fluid interfaces. For example, a complete separation of micro-particles was demonstrated by using a three-stream multiphase flow configuration. PMID- 27190568 TI - Going beyond 20 MUm-sized channels for studying red blood cell phase separation in microfluidic bifurcations. AB - Despite the development of microfluidics, experimental challenges are considerable for achieving a quantitative study of phase separation, i.e., the non-proportional distribution of Red Blood Cells (RBCs) and suspending fluid, in microfluidic bifurcations with channels smaller than 20 MUm. Yet, a basic understanding of phase separation in such small vessels is needed for understanding the coupling between microvascular network architecture and dynamics at larger scale. Here, we present the experimental methodologies and measurement techniques developed for that purpose for RBC concentrations (tube hematocrits) ranging between 2% and 20%. The maximal RBC velocity profile is directly measured by a temporal cross-correlation technique which enables to capture the RBC slip velocity at walls with high resolution, highlighting two different regimes (flat and more blunted ones) as a function of RBC confinement. The tube hematocrit is independently measured by a photometric technique. The RBC and suspending fluid flow rates are then deduced assuming the velocity profile of a Newtonian fluid with no slip at walls for the latter. The accuracy of this combination of techniques is demonstrated by comparison with reference measurements and verification of RBC and suspending fluid mass conservation at individual bifurcations. The present methodologies are much more accurate, with less than 15% relative errors, than the ones used in previous in vivo experiments. Their potential for studying steady state phase separation is demonstrated, highlighting an unexpected decrease of phase separation with increasing hematocrit in symmetrical, but not asymmetrical, bifurcations and providing new reference data in regimes where in vitro results were previously lacking. PMID- 27190565 TI - Future microfluidic and nanofluidic modular platforms for nucleic acid liquid biopsy in precision medicine. AB - Nucleic acid biomarkers have enormous potential in non-invasive diagnostics and disease management. In medical research and in the near future in the clinics, there is a great demand for accurate miRNA, mRNA, and ctDNA identification and profiling. They may lead to screening of early stage cancer that is not detectable by tissue biopsy or imaging. Moreover, because their cost is low and they are non-invasive, they can become a regular screening test during annual checkups or allow a dynamic treatment program that adjusts its drug and dosage frequently. We briefly review a few existing viral and endogenous RNA assays that have been approved by the Federal Drug Administration. These tests are based on the main nucleic acid detection technologies, namely, quantitative reverse transcription polymerase chain reaction (PCR), microarrays, and next-generation sequencing. Several of the challenges that these three technologies still face regarding the quantitative measurement of a panel of nucleic acids are outlined. Finally, we review a cluster of microfluidic technologies from our group with potential for point-of-care nucleic acid quantification without nucleic acid amplification, designed to overcome specific limitations of current technologies. We suggest that integration of these technologies in a modular design can offer a low-cost, robust, and yet sensitive/selective platform for a variety of precision medicine applications. PMID- 27190569 TI - A label-free and high-throughput separation of neuron and glial cells using an inertial microfluidic platform. AB - While neurons and glial cells both play significant roles in the development and therapy of schizophrenia, their specific contributions are difficult to differentiate because the methods used to separate neurons and glial cells are ineffective and inefficient. In this study, we reported a high-throughput microfluidic platform based on the inertial microfluidic technique to rapidly and continuously separate neurons and glial cells from dissected brain tissues. The optimal working condition for an inertial biochip was investigated and evaluated by measuring its separation under different flow rates. Purified and enriched neurons in a primary neuron culture were verified by confocal immunofluorescence imaging, and neurons performed neurite growth after separation, indicating the feasibility and biocompatibility of an inertial separation. Phencyclidine disturbed the neuroplasticity and neuron metabolism in the separated and the unseparated neurons, with no significant difference. Apart from isolating the neurons, purified and enriched viable glial cells were collected simultaneously. This work demonstrates that an inertial microchip can provide a label-free, high throughput, and harmless tool to separate neurological primary cells. PMID- 27190570 TI - On utilizing alternating current-flow field effect transistor for flexibly manipulating particles in microfluidics and nanofluidics. AB - By imposing a biased gate voltage to a center metal strip, arbitrary symmetry breaking in induced-charge electroosmotic flow occurs on the surface of this planar gate electrode, a phenomenon termed as AC-flow field effect transistor (AC FFET). In this work, the potential of AC-FFET with a shiftable flow stagnation line to flexibly manipulate micro-nano particle samples in both a static and continuous flow condition is demonstrated via theoretical analysis and experimental validation. The effect of finite Debye length of induced double layer and applied field frequency on the manipulating flexibility factor for static condition is investigated, which indicates AC-FFET turns out to be more effective for achieving a position-controllable concentrating of target nanoparticle samples in nanofluidics compared to the previous trial in microfluidics. Besides, a continuous microfluidics-based particle concentrator/director is developed to deal with incoming analytes in dynamic condition, which exploits a design of tandem electrode configuration to consecutively flow focus and divert incoming particle samples to a desired downstream branch channel, as prerequisite for a following biochemical analysis. Our physical demonstrations with AC-FFET prove valuable for innovative designs of flexible electrokinetic frameworks, which can be conveniently integrated with other microfluidic or nanofluidic components into a complete lab-on-chip diagnostic platform due to a simple electrode structure. PMID- 27190571 TI - Microarray-integrated optoelectrofluidic immunoassay system. AB - A microarray-based analytical platform has been utilized as a powerful tool in biological assay fields. However, an analyte depletion problem due to the slow mass transport based on molecular diffusion causes low reaction efficiency, resulting in a limitation for practical applications. This paper presents a novel method to improve the efficiency of microarray-based immunoassay via an optically induced electrokinetic phenomenon by integrating an optoelectrofluidic device with a conventional glass slide-based microarray format. A sample droplet was loaded between the microarray slide and the optoelectrofluidic device on which a photoconductive layer was deposited. Under the application of an AC voltage, optically induced AC electroosmotic flows caused by a microarray-patterned light actively enhanced the mass transport of target molecules at the multiple assay spots of the microarray simultaneously, which reduced tedious reaction time from more than 30 min to 10 min. Based on this enhancing effect, a heterogeneous immunoassay with a tiny volume of sample (5 MUl) was successfully performed in the microarray-integrated optoelectrofluidic system using immunoglobulin G (IgG) and anti-IgG, resulting in improved efficiency compared to the static environment. Furthermore, the application of multiplex assays was also demonstrated by multiple protein detection. PMID- 27190573 TI - Role of Vanadium in Cellular and Molecular Immunology: Association with Immune Related Inflammation and Pharmacotoxicology Mechanisms. AB - Over the last decade, a diverse spectrum of vanadium compounds has arisen as anti inflammatory therapeutic metallodrugs targeting various diseases. Recent studies have demonstrated that select well-defined vanadium species are involved in many immune-driven molecular mechanisms that regulate and influence immune responses. In addition, advances in cell immunotherapy have relied on the use of metallodrugs to create a "safe," highly regulated, environment for optimal control of immune response. Emerging findings include optimal regulation of B/T cell signaling and expression of immune suppressive or anti-inflammatory cytokines, critical for immune cell effector functions. Furthermore, in-depth perusals have explored NF-kappaB and Toll-like receptor signaling mechanisms in order to enhance adaptive immune responses and promote recruitment or conversion of inflammatory cells to immunodeficient tissues. Consequently, well-defined vanadium metallodrugs, poised to access and resensitize the immune microenvironment, interact with various biomolecular targets, such as B cells, T cells, interleukin markers, and transcription factors, thereby influencing and affecting immune signaling. A synthetically formulated and structure-based (bio)chemical reactivity account of vanadoforms emerges as a plausible strategy for designing drugs characterized by selectivity and specificity, with respect to the cellular molecular targets intimately linked to immune responses, thereby giving rise to a challenging field linked to the development of immune system vanadodrugs. PMID- 27190574 TI - Oxidative Stress in the Developing Rat Brain due to Production of Reactive Oxygen and Nitrogen Species. AB - Oxidative stress after birth led us to localize reactive oxygen and nitrogen species (RONS) production in the developing rat brain. Brains were assessed a day prenatally and on postnatal days 1, 2, 4, 8, 14, 30, and 60. Oxidation of dihydroethidium detected superoxide; 6-carboxy-2',7'-dichlorodihydrofluorescein diacetate revealed hydrogen peroxide; immunohistochemical proof of nitrotyrosine and carboxyethyllysine detected peroxynitrite formation and lipid peroxidation, respectively. Blue autofluorescence detected protein oxidation. The foetuses showed moderate RONS production, which changed cyclically during further development. The periods and sites of peak production of individual RONS differed, suggesting independent generation. On day 1, neuronal/glial RONS production decreased indicating that increased oxygen concentration after birth did not cause oxidative stress. Dramatic changes in the amount and the sites of RONS production occurred on day 4. Nitrotyrosine detection reached its maximum. Day 14 represented other vast alterations in RONS generation. Superoxide production in arachnoidal membrane reached its peak. From this day on, the internal elastic laminae of blood vessels revealed the blue autofluorescence. The adult animals produced moderate levels of superoxide; all other markers reached their minimum. There was a strong correlation between detection of nitrotyrosine and carboxyethyllysine probably caused by lipid peroxidation initiated with RONS. PMID- 27190572 TI - Intracerebral Hemorrhage, Oxidative Stress, and Antioxidant Therapy. AB - Hemorrhagic stroke is a common and severe neurological disorder and is associated with high rates of mortality and morbidity, especially for intracerebral hemorrhage (ICH). Increasing evidence demonstrates that oxidative stress responses participate in the pathophysiological processes of secondary brain injury (SBI) following ICH. The mechanisms involved in interoperable systems include endoplasmic reticulum (ER) stress, neuronal apoptosis and necrosis, inflammation, and autophagy. In this review, we summarized some promising advances in the field of oxidative stress and ICH, including contained animal and human investigations. We also discussed the role of oxidative stress, systemic oxidative stress responses, and some research of potential therapeutic options aimed at reducing oxidative stress to protect the neuronal function after ICH, focusing on the challenges of translation between preclinical and clinical studies, and potential post-ICH antioxidative therapeutic approaches. PMID- 27190575 TI - Antioxidant and Anti-Inflammatory Effects of Coenzyme Q10 on L-Arginine-Induced Acute Pancreatitis in Rat. AB - This study was aimed at evaluating the protective effect of coenzyme Q10 on L arginine-induced acute pancreatitis in rats regarding biomarkers and morphologic changes. Thirty-two male Sprague-Dawley rats were divided into 4 equal groups. Control group received intraperitoneal normal saline, while in sham and experimental groups 1 and 2 pancreatitis was induced with L-arginine. E1 and E2 groups were treated with a single dose of 100 and 200 mg/kg Q10, respectively. Serum lipase and amylase, along with pancreas IL-10, IL-1beta, and TNF-alpha, were measured. For evaluation of oxidative stress, pancreatic superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), and myeloperoxidase (MPO) were assessed. Histopathological examination for morphologic investigation was conducted. Serum amylase and lipase, as well as TNF-alpha and IL-1beta cytokines, reverted with administration of Q10 in consistence with dosage. In contrast, Q10 assisted in boosting of IL-10 with higher dosage (200 mg/kg). A similar pattern for oxidative stress markers was noticed. Both MDA and MPO levels declined with increased dosage, contrary to elevation of SOD and GSH. Histopathology was in favor of protective effects of Q10. Our findings proved the amelioration of pancreatic injury by Q10, which suggest the anti-inflammatory and antioxidant property of Q10 and its potential therapeutic role. PMID- 27190577 TI - Liver resection for intermediate hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China. The Barcelona Clinic Liver Cancer (BCLC) staging system is regarded as the gold standard staging system for HCC, classifying HCC as early, intermediate, or advanced. For intermediate HCC, trans-catheter arterial chemoembolization (TACE) is recommended as the optimal strategy by the BCLC guideline. This review investigates whether liver resection is better than TACE for intermediate HCC. Based on published studies, we compare the survival benefits and complications of liver resection and TACE for intermediate HCC. We also compare the survival benefits of liver resection in early and intermediate HCC. We find that liver resection can achieve better or at least comparable survival outcomes compared with TACE for intermediate HCC; however, we do not observe a significant difference between liver resection and TACE in terms of safety and morbidity. We conclude that liver resection may improve the short- and long-term survival of carefully selected intermediate HCC patients, and the procedure may be safely performed in the management of intermediate HCC. PMID- 27190579 TI - Co-treatment with pegylated interferon alfa-2a and entecavir for hepatitis D: A randomized trial. AB - AIM: To investigate the efficacy of pegylated interferon alfa (PEG-IFNalpha) therapy with and without entecavir in patients with chronic hepatitis D. METHODS: Forty hepatitis D virus (HDV) RNA positive patients were randomized to receive either PEG-IFNalpha-2a 180 MUg weekly in combination with entecavir 0.5 mg daily (n = 21) or PEG-IFNalpha alone (n =19). Patients who failed to show 2 log reduction in HDV RNA level at 24 wk of treatment, or had detectable HDV RNA at 48 wk of therapy were considered as treatment failure. Treatment was continued for 72 wk in the rest of the patients. All the patients were followed for 24 wk post treatment. Intention to treat analysis was performed. RESULTS: The mean age of the patients was 26.7 +/- 6.8 years, 31 were male. Two log reduction in HDV RNA levels at 24 wk of therapy was achieved in 9 (43%) patients receiving combination therapy and 12 (63%) patients receiving PEG-IFNalpha alone (P = 0.199). Decline in hepatitis B surface antigen (HBsAg) levels was insignificant. At the end of treatment, HDV RNA was negative in 8 patients (38%) receiving combination therapy and 10 patients (53%) receiving PEG-IFNalpha-2a alone. Virological response persisted in 7 (33%) and 8 (42%) patients, respectively at the end of the 24 wk follow-up period. One responder patient in the combination arm lost HBsAg and became hepatitis B surface antibody positive. Six out of 14 baseline hepatitis B e antigen reactive patients seroconverted and four of these seroconverted patients had persistent HDV RNA clearance. CONCLUSION: Administration of PEG IFNalpha-2a with or without entecavir, resulted in persistent HDV RNA clearance in 37% of patients. The addition of entecavir did not improve the overall response. PMID- 27190576 TI - Assessment of Mitochondrial Dysfunction and Monoamine Oxidase Contribution to Oxidative Stress in Human Diabetic Hearts. AB - Mitochondria-related oxidative stress is a pathomechanism causally linked to coronary heart disease (CHD) and diabetes mellitus (DM). Recently, mitochondrial monoamine oxidases (MAOs) have emerged as novel sources of oxidative stress in the cardiovascular system and experimental diabetes. The present study was purported to assess the mitochondrial impairment and the contribution of MAOs related oxidative stress to the cardiovascular dysfunction in coronary patients with/without DM. Right atrial appendages were obtained from 75 patients randomized into 3 groups: (1) Control (CTRL), valvular patients without CHD; (2) CHD, patients with confirmed CHD; and (3) CHD-DM, patients with CHD and DM. Mitochondrial respiration was measured by high-resolution respirometry and MAOs expression was evaluated by RT-PCR and immunohistochemistry. Hydrogen peroxide (H2O2) emission was assessed by confocal microscopy and spectrophotometrically. The impairment of mitochondrial respiration was substrate-independent in CHD-DM group. MAOs expression was comparable among the groups, with the predominance of MAO-B isoform but no significant differences regarding oxidative stress were detected by either method. Incubation of atrial samples with MAOs inhibitors significantly reduced the H2O2 in all groups. In conclusion, abnormal mitochondrial respiration occurs in CHD and is more severe in DM and MAOs contribute to oxidative stress in human diseased hearts with/without DM. PMID- 27190578 TI - Combined acoustic radiation force impulse, aminotransferase to platelet ratio index and Forns index assessment for hepatic fibrosis grading in hepatitis B. AB - AIM: To investigate the combined diagnostic accuracy of acoustic radiation force impulse (ARFI), aspartate aminotransferase to platelet ratio index (APRI) and Forns index for a non-invasive assessment of liver fibrosis in patients with chronic hepatitis B (CHB). METHODS: In this prospective study, 206 patients had CHB with liver fibrosis stages F0-F4 classified by METAVIR and 40 were healthy volunteers were measured by ARFI, APRI and Forns index separately or combined as indicated. RESULTS: ARFI, APRI or Forns index demonstrated a significant correlation with the histological stage (all P < 0.001). According to the AUROC of ARFI and APRI for evaluating fibrotic stages more than F2, ARFI showed an enhanced diagnostic accuracy than APRI (P < 0.05). The combined measurement of ARFI and APRI exhibited better accuracy than ARFI alone when evaluating >= F2 fibrotic stage (Z = 2.77, P = 0.006). Combination of ARFI, APRI and Forns index did not obviously improve the diagnostic accuracy compared to the combination of ARFI and APRI (Z = 0.958, P = 0.338). CONCLUSION: ARFI + APRI showed enhanced diagnostic accuracy than ARFI or APRI alone for significant liver fibrosis and ARFI + APRI + Forns index shows the same effect with ARFI + APRI. PMID- 27190580 TI - Direct acting antiviral therapy is curative for chronic hepatitis C/autoimmune hepatitis overlap syndrome. AB - Autoimmune phenomena are common in patients with chronic hepatitis C. Management of chronic hepatitis C/autoimmune hepatitis syndrome has until recently been problematic due to the adverse effects of interferon on autoimmune processes and immunosuppression on viral replication. In this report we describe 3 patients with chronic hepatitis C/autoimmune hepatitis overlap syndrome who responded rapidly to direct acting anti-viral therapy. The resolution of the autoimmune process supports a direct viral role in its pathophysiology. PMID- 27190582 TI - Role of Raman spectroscopy and surface enhanced Raman spectroscopy in colorectal cancer. AB - Colorectal cancer (CRC) is the fourth most common cancer in the United Kingdom and is the second largest cause of cancer related death in the United Kingdom after lung cancer. Currently in the United Kingdom there is not a diagnostic test that has sufficient differentiation between patients with cancer and those without cancer so the current referral system relies on symptomatic presentation in a primary care setting. Raman spectroscopy and surface enhanced Raman spectroscopy (SERS) are forms of vibrational spectroscopy that offer a non destructive method to gain molecular information about biological samples. The techniques offer a wide range of applications from in vivo or in vitro diagnostics using endoscopic probes, to the use of micro-spectrometers for analysis of biofluids. The techniques have the potential to detect molecular changes prior to any morphological changes occurring in the tissue and therefore could offer many possibilities to aid the detection of CRC. The purpose of this review is to look at the current state of diagnostic technology in the United Kingdom. The development of Raman spectroscopy and SERS in clinical applications relation for CRC will then be discussed. Finally, future areas of research of Raman/SERS as a clinical tool for the diagnosis of CRC are also discussed. PMID- 27190581 TI - MicroRNA in rectal cancer. AB - In rectal cancer, one of the most common cancers worldwide, the proper staging of the disease determines the subsequent therapy. For those with locally advanced rectal cancer, a neoadjuvant chemoradiotherapy (CRT) is recommended before any surgery. However, response to CRT ranges from complete response (responders) to complete resistance (non-responders). To date we are not able to separate in advance the first group from the second, due to the absence of a valid biomarker. Therefore all patients receive the same therapy regardless of whether they reap benefits. On the other hand almost all patients receive a surgical resection after the CRT, although a watch-and-wait procedure or an endoscopic resection might be sufficient for those who responded well to the CRT. Being highly conserved regulators of gene expression, microRNAs (miRNAs) seem to be promising candidates for biomarkers. Many studies have been analyzing the miRNAs expressed in rectal cancer tissue to determine a specific miRNA profile for the ailment. Unfortunately, there is only a small overlap of identified miRNAs between different studies, posing the question as to whether different methods or differences in tissue storage may contribute to that fact or if the results simply are not reproducible, due to unknown factors with undetected influences on miRNA expression. Other studies sought to find miRNAs which correlate to clinical parameters (tumor grade, nodal stage, metastasis, survival) and therapy response. Although several miRNAs seem to have an impact on the response to CRT or might predict nodal stage, there is still only little overlap between different studies. We here aimed to summarize the current literature on rectal cancer and miRNA expression with respect to the different relevant clinical parameters. PMID- 27190584 TI - Multitarget stool DNA for colorectal cancer screening: A review and commentary on the United States Preventive Services Draft Guidelines. AB - Multitarget stool DNA (mt-sDNA) testing was approved for average risk colorectal cancer (CRC) screening by the United States Food and Drug Administration and thereafter reimbursed for use by the Medicare program (2014). The United States Preventive Services Task Force (USPSTF) October 2015 draft recommendation for CRC screening included mt-sDNA as an "alternative" screening test that "may be useful in select clinical circumstances", despite its very high sensitivity for early stage CRC. The evidence supporting mt-sDNA for routine screening use is robust. The clinical efficacy of mt-sDNA as measured by sensitivity, specificity, life years gained (LYG), and CRC deaths averted is similar to or exceeds that of the other more specifically recommended screening options included in the draft document, especially those requiring annual testing adherence. In a population with primarily irregular screening participation, tests with the highest point sensitivity and reasonable specificity are more likely to favorably impact CRC related morbidity and mortality than those depending on annual adherence. This paper reviews the evidence supporting mt-sDNA for routine screening and demonstrates, using USPSTF's modeling data, that mt-sDNA at three-year intervals provides significant clinical net benefits and fewer complications per LYG than annual fecal immunochemical testing, high sensitivity guaiac based fecal occult blood testing and 10-year colonoscopy screening. PMID- 27190583 TI - Current adjuvant treatment modalities for gastric cancer: From history to the future. AB - The discrepancy between the surgical technique and the type of adjuvant chemotherapy used in clinical trials and patient outcomes in terms of overall survival rates has led to the generation of different adjuvant treatment protocols in distinct parts of the world. The adjuvant treatment recommendation is generally chemoradiotherapy in the United States, perioperative chemotherapy in the United Kingdom and parts of Europe, and chemotherapy in Asia. These options mainly rely on the United States Intergroup-0116, United Kingdom British Medical Research Council Adjuvant Gastric Infusional Chemotherapy, and the Asian Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer and Capecitabine and Oxaliplatin Adjuvant Study in Stomach Cancer trials. However, the benefits were evident for only certain patients, which were not very homogeneous regarding the type of surgery, chemotherapy regimens, and stage of disease. Whether the dissimilarities in survival are attributable to surgical technique or intrinsic biological differences is a subject of debate. Regardless of the extent of surgery, multimodal therapy may offer modest survival advantage at least for diseases with lymph node involvement. Moreover, in the era of individualized treatment for most of the other cancer types, identification of special subgroups comprising those who will derive more or no benefit from adjuvant therapy merits further investigation. The aim of this review is to reveal the historical evolution and future reflections of adjuvant treatment modalities for resected gastric cancer patients. PMID- 27190585 TI - Urinary metabolites as noninvasive biomarkers of gastrointestinal diseases: A clinical review. AB - The diagnosis of gastrointestinal (GI) disorders is usually based on invasive techniques such as endoscopy. A key important factor in GI cancer is early diagnosis which warrants development of non- or less-invasive diagnostic techniques. In addition, monitoring and surveillance are other important parts in the management of GI diseases. Metabolomics studies with nuclear magnetic resonance and mass spectrometry can measure the concentration of more than 3000 chemical compounds in the urine providing possible chemical signature in different diseases and during health. In this review, we discuss the urinary metabolomics signature of different GI diseases including GI cancer and elaborate on how these biomarkers could be used for the classification, early diagnosis and the monitoring of the patients. Moreover, we discuss future directions of this still evolving field of research. PMID- 27190586 TI - Non-surgical factors influencing lymph node yield in colon cancer. AB - There are numerous factors which can affect the lymph node (LN) yield in colon cancer specimens. The aim of this paper was to identify both modifiable and non modifiable factors that have been demonstrated to affect colonic resection specimen LN yield and to summarise the pertinent literature on these topics. A literature review of PubMed was performed to identify the potential factors which may influence the LN yield in colon cancer resection specimens. The terms used for the search were: LN, lymphadenectomy, LN yield, LN harvest, LN number, colon cancer and colorectal cancer. Both non-modifiable and modifiable factors were identified. The review identified fifteen non-surgical factors: (13 non modifiable, 2 modifiable) which may influence LN yield. LN yield is frequently reduced in older, obese patients and those with male sex and increased in patients with right sided, large, and poorly differentiated tumours. Patient ethnicity and lower socioeconomic class may negatively influence LN yield. Pre operative tumour tattooing appears to increase LN yield. There are many factors that potentially influence the LN yield, although the strength of the association between the two varies greatly. Perfecting oncological resection and pathological analysis remain the cornerstones to achieving good quality and quantity LN yields in patients with colon cancer. PMID- 27190587 TI - Intensity modulated radiation therapy with simultaneous integrated boost based dose escalation on neoadjuvant chemoradiation therapy for locally advanced distal esophageal adenocarcinoma. AB - AIM: To evaluate impact of radiation therapy dose escalation through intensity modulated radiation therapy with simultaneous integrated boost (IMRT-SIB). METHODS: We retrospectively reviewed the patients who underwent four-dimensional based IMRT-SIB-based neoadjuvant chemoradiation protocol. During the concurrent chemoradiation therapy, radiation therapy was through IMRT-SIB delivered in 28 consecutive daily fractions with total radiation doses of 56 Gy to tumor and 5040 Gy dose-painted to clinical tumor volume, with a regimen at the discretion of the treating medical oncologist. This was followed by surgical tumor resection. We analyzed pathological completion response (pCR) rates its relationship with overall survival and event-free survival. RESULTS: Seventeen patients underwent dose escalation with the IMRT-SIB protocol between 2007 and 2014 and their records were available for analysis. Among the IMRT-SIB-treated patients, the toxicity appeared mild, the most common side effects were grade 1-3 esophagitis (46%) and pneumonitis (11.7%). There were no cardiac events. The Ro resection rate was 94% (n = 16), the pCR rate was 47% (n = 8), and the postoperative morbidity was zero. There was one mediastinal failure found, one patient had local failure at the anastomosis site, and the majority of failures were distant in the lung or bone. The 3-year disease-free survival and overall survival rates were 41% (n = 7) and 53% (n = 9), respectively. CONCLUSION: The dose escalation through IMRT-SIB in the chemoradiation regimen seems responsible for down-staging the distal esophageal with well-tolerated complications. PMID- 27190589 TI - Pyrrolo[2,3-c]pyridines as Imaging Agents for Neurofibrilary Tangles. PMID- 27190588 TI - Therapeutics from Adult Stem Cells and the Hype Curve. AB - The Gartner curve for regenerative and stem cell therapeutics is currently climbing out of the "trough of disillusionment" and into the "slope of enlightenment". Understanding that the early years of stem cell therapy relied on the model of embryonic stem cells (ESCs), and then moved into a period of the overhype of induced pluripotent stem cells (iPSCs), instead of using the model of 40 years of success, i.e. adult stem cells used in bone marrow transplants, the field of stem cell therapy has languished for years, trying to move beyond the early and poorly understood success of bone marrow transplants. Recent studies in the lab and clinic show that adult stem cells of various types, and the molecules that they release, avoid the issues associated with ESCs and iPSCs and lead to better therapeutic outcomes and into the slope of enlightenment. PMID- 27190590 TI - Inhibitors of Renal Outer Medullary Potassium Channel. PMID- 27190591 TI - Novel Inhibitors of Toxin HipA Reduce Multidrug Tolerant Persisters. AB - Persisters are a small fraction of drug-tolerant bacteria without any genotype variations. Their existence in many life-threatening infectious diseases presents a major challenge to antibiotic therapy. Persistence is highly related to toxin antitoxin modules. HipA (high persistence A) was the first toxin found to contribute to Escherichia coli persistence. In this study, we used structure based virtual screening for HipA inhibitors discovery and identified several novel inhibitors of HipA that remarkably reduced E. coli persistence. The most potent one decreased the persister fraction by more than five-fold with an in vitro K D of 270 +/- 90 nM and an ex vivo EC50 of 46 +/- 2 and 28 +/- 1 MUM for ampicillin and kanamycin screening, respectively. These findings demonstrated that inhibition of toxin can reduce bacterial persistence independent of the antibiotics used and provided a framework for persistence treatment by interfering with the toxin-antitoxin modules. PMID- 27190592 TI - Discovery of a Selective Series of Inhibitors of Plasmodium falciparum HDACs. AB - The identification of a new series of P. falciparum growth inhibitors is described. Starting from a series of known human class I HDAC inhibitors a SAR exploration based on growth inhibitory activity in parasite and human cells-based assays led to the identification of compounds with submicromolar inhibition of P. falciparum growth (EC50 < 500 nM) and good selectivity over the activity of human HDAC in cells (up to >50-fold). Inhibition of parasital HDACs as the mechanism of action of this new class of selective growth inhibitors is supported by hyperacetylation studies. PMID- 27190594 TI - Discovery of IWP-051, a Novel Orally Bioavailable sGC Stimulator with Once-Daily Dosing Potential in Humans. AB - In recent years, soluble guanylate cyclase (sGC, EC 4.6.1.2) has emerged as an attractive therapeutic target for treating cardiovascular diseases and diseases associated with fibrosis and end-organ failure. Herein, we describe our design and synthesis of a series of 4-hydroxypyrimidine sGC stimulators starting with an internally discovered lead. Our efforts have led to the discovery of IWP-051, a molecule that achieves good alignment of potency, stability, selectivity, and pharmacodynamic effects while maintaining favorable pharmacokinetic properties with once-daily dosing potential in humans. PMID- 27190593 TI - Functionalized N,N-Diphenylamines as Potent and Selective EPAC2 Inhibitors. AB - N,N-Diphenylamines were discovered as potent and selective EPAC2 inhibitors. A study was conducted to determine the structure-activity relationships in a series of inhibitors of which several compounds displayed submicromolar potencies. Selectivity over the related EPAC1 protein was also demonstrated. Computational modeling reveals an allosteric site that is distinct from the cAMP binding domain shared by both EPAC isoforms, providing a theory with regards to subtype selectivity. PMID- 27190595 TI - Design, Synthesis, and Evaluation of Donepezil-Like Compounds as AChE and BACE-1 Inhibitors. AB - An ecofriendly synthetic pathway for the synthesis of donepezil precursors is described. Alternative energy sources were used for the total synthesis in order to improve yields, regioselectively, and rate of each synthetic step and to reduce the coproduction of waste at the same time. For all products, characterized by an improved structural rigidity respect to donepezil, the inhibitor activity on AChE, the selectivity vs BuChE, the side-activity on BACE 1, and the effect on SHSY-5Y neuroblastoma cells viability were tested. Two potential new lead compounds for a dual therapeutic strategy against Alzheimer's disease were envisaged. PMID- 27190596 TI - Discovery of a Highly Potent and Selective Indenoindolone Type 1 Pan-FLT3 Inhibitor. AB - For a subpopulation of acute myeloid leukemia (AML) patients, the mutationally activated tyrosine kinase FLT3, has emerged as a promising target for therapy. The development of drug resistance due to mutation is a growing concern for mutant FLT3 inhibitors, such as PKC412, Quizartinib, PLX3397, and Crenolanib. Thus, there is a need to develop novel FLT3 inhibitors that overcome these mutations. Here we report the development of a novel type I ATP competitive inhibitor, JH-IX-179, that is extremely potent and selective for FLT3. JH-IX-179 also has the highest affinity for three constitutively active isoforms of FLT3 (FLT3-ITD, FLT3-N841I, and FLT3-D835V) compared to a panel 456 other kinases. The unique and specific kinase inhibition profile suggests that this chemotype may represent an attractive starting point for the development of further improved FLT3 inhibitors with therapeutic potential in tumors harboring deregulated FLT3 activity. PMID- 27190597 TI - Autoradiographic Evaluation of [(18)F]FECUMI-101, a High Affinity 5-HT1AR Ligand in Human Brain. AB - [(18)F]FECUMI-101 ([(18)F]1) is a 5HT1AR ligand demonstrating specific binding in brain regions corresponding to the distribution of 5-HT1AR in baboons. However, we detected moderate uptake of [(18)F]1 in baboon thalamus, a brain region lacking 5-HT1AR. We sought to investigate the relative binding of [(18)F]1 to 5 HT1AR, alpha1R, and 5-HT7R in vitro. Using autoradiography in human brain sections, specific binding of [(18)F]1 to 5-HT1AR was confirmed. However, [(18)F]1 also showed 26% binding to alpha1R in PFC. The hippocampal formation exhibited 51% and 92% binding of [(18)F]1 to alpha1R and 5-HT1AR, respectively. Thalamus and cerebellum showed very little binding. There is no measurable specific binding of [(18)F]1 to 5-HT7R and no effect of temperature on [(18)F]1 specific binding to 5-HT1AR or alpha1R. These results indicate that, while [(18)F]FECUMI-101 is not a completely selective 5-HT1AR ligand for receptor quantification, it may be useful for occupancy measurements of drugs acting at 5 HT1AR in vivo. PMID- 27190598 TI - Structural Requirements and Docking Analysis of Amidine-Based Sphingosine Kinase 1 Inhibitors Containing Oxadiazoles. AB - Sphingosine 1-phosphate (S1P) is a potent growth-signaling lipid that has been implicated in cancer progression, inflammation, sickle cell disease, and fibrosis. Two sphingosine kinases (SphK1 and 2) are the source of S1P; thus, inhibitors of the SphKs have potential as targeted cancer therapies and will help to clarify the roles of S1P and the SphKs in other hyperproliferative diseases. Recently, we reported a series of amidine-based inhibitors with high selectivity for SphK1 and potency in the nanomolar range. However, these inhibitors display a short half-life. With the goal of increasing metabolic stability and maintaining efficacy, we designed an analogous series of molecules containing oxadiazole moieties. Generation of a library of molecules resulted in the identification of the most selective inhibitor of SphK1 reported to date (705-fold selectivity over SphK2), and we found that potency and selectivity vary significantly depending on the particular oxadiazole isomer employed. The best inhibitors were subjected to in silico molecular dynamics docking analysis, which revealed key insights into the binding of amidine-based inhibitors by SphK1. Herein, the design, synthesis, biological evaluation, and docking analysis of these molecules are described. PMID- 27190599 TI - Identification of a Potent and Selective GPR4 Antagonist as a Drug Lead for the Treatment of Myocardial Infarction. AB - GPR4, a pH-sensing G protein-coupled receptor, is highly expressed in endothelial cells and may be activated in myocardial infarction due the decreased tissue pH. We are interested in GPR4 antagonists as potential effective pharmacologic tools and/or drug leads for the treatment of myocardial infarction. We investigated the structure-activity relationship of a known GPR4 antagonist 1 as a lead compound to identify 3b as the first potent and selective GPR4 antagonist, whose effectiveness was demonstrated in a mouse myocardial infarction model. PMID- 27190600 TI - Discovery of Novel Tricyclic Heterocycles as Potent and Selective DPP-4 Inhibitors for the Treatment of Type 2 Diabetes. AB - In our efforts to develop second generation DPP-4 inhibitors, we endeavored to identify distinct structures with long-acting (once weekly) potential. Taking advantage of X-ray cocrystal structures of sitagliptin and other DPP-4 inhibitors, such as alogliptin and linagliptin bound to DPP-4, and aided by molecular modeling, we designed several series of heterocyclic compounds as initial targets. During their synthesis, an unexpected chemical transformation provided a novel tricyclic scaffold that was beyond our original design. Capitalizing on this serendipitous discovery, we have elaborated this scaffold into a very potent and selective DPP-4 inhibitor lead series, as highlighted by compound 17c. PMID- 27190601 TI - Structure-Activity Relationship Studies of Isomeric 2,4-Diaminoquinazolines on beta-Amyloid Aggregation Kinetics. AB - A library of isomeric 2,4-diaminoquinazoline (DAQ) derivatives were synthesized and evaluated for antiaggregation potential toward Abeta40/42. Structure-activity relationship data identified compound 3k (N (4)-(4-bromobenzyl)quinazoline-2,4 diamine) with a 4-bromobenzyl substituent as the most potent inhibitor (Abeta40 IC50 = 80 nM) and was almost 18-fold more potent compared to the reference agent curcumin (Abeta40 IC50 = 1.5 MUM). The corresponding N (2)-isomer 4k (N (2)-(4 bromobenzyl)quinazoline-2,4-diamine) was also able to prevent Abeta aggregation (Abeta40 IC50 = 1.7 MUM). However, compound 4k exhibited superior inhibition of Abeta42 aggregation (Abeta42 IC50 = 1.7 MUM) compared to compound 3k (Abeta42 IC50 = 14.8 MUM) and was ~1.8-fold more potent compared to curcumin (Abeta42 IC50 = 3.1 MUM). These results were supported by Abeta aggregation kinetics investigations and transmission electron microscopy studies, which demonstrate the suitability of DAQ ring system to develop antiamyloid agents as pharmacological tools to study Abeta aggregation. PMID- 27190602 TI - Structure-Based Design of 1,4-Dibenzoylpiperazines as beta-Catenin/B-Cell Lymphoma 9 Protein-Protein Interaction Inhibitors. AB - A small-molecule inhibitor with a 1,4-dibenzoylpiperazine scaffold was designed to match the critical binding elements in the beta-catenin/B-cell lymphoma 9 (BCL9) protein-protein interaction interface. Inhibitor optimization led to a potent inhibitor that can disrupt the beta-catenin/BCL9 interaction and exhibit 98-fold selectivity over the beta-catenin/cadherin interaction. The binding mode of new inhibitors was characterized by structure-activity relationships and site directed mutagenesis studies. Cell-based studies demonstrated that this series of inhibitors can selectively suppress canonical Wnt signaling and inhibit growth of Wnt/beta-catenin-dependent cancer cells. PMID- 27190603 TI - Utilization of Structure-Based Design to Identify Novel, Irreversible Inhibitors of EGFR Harboring the T790M Mutation. AB - A novel series of covalent inhibitors of EGFR (epidermal growth factor receptor) kinase was discovered through a combination of subset screening and structure based design. These compounds preferentially inhibit mutant forms of EGFR (activating mutant and T790M mutant) over wild-type EGFR in cellular assays measuring EGFR autophosphorylation and proliferation, suggesting an improved therapeutic index in non-small cell lung cancer patients would be achievable relative to established EGFR inhibitors. We describe our design approaches, resulting in the identification of the lead compound 5, and our efforts to develop an understanding of the structure-activity relationships within this series. In addition, strategies to overcome challenges around metabolic stability and aqueous solubility are discussed. Despite limitations in its physical properties, 5 is orally bioavailable in mice and demonstrates pronounced antitumor activity in in vivo models of mutant EGFR-driven cancers. PMID- 27190604 TI - Discovery of Potent, Orally Bioavailable Inhibitors of Human Cytomegalovirus. AB - A high-throughput screen based on a viral replication assay was used to identify inhibitors of the human cytomegalovirus. Using this approach, hit compound 1 was identified as a 4 MUM inhibitor of HCMV that was specific and selective over other herpes viruses. Time of addition studies indicated compound 1 exerted its antiviral effect early in the viral life cycle. Mechanism of action studies also revealed that this series inhibited infection of MRC-5 and ARPE19 cells by free virus and via direct cell-to-cell spread from infected to uninfected cells. Preliminary structure-activity relationships demonstrated that the potency of compound 1 could be improved to a low nanomolar level, but metabolic stability was a key optimization parameter for this series. A strategy focused on minimizing metabolic hydrolysis of the N1-amide led to an alternative scaffold in this series with improved metabolic stability and good pharmacokinetic parameters in rat. PMID- 27190606 TI - Discovery of a Fluorinated Enigmol Analog with Enhanced in Vivo Pharmacokinetic and Anti-Tumor Properties. AB - The orally bioavailable 1-deoxy-sphingosine analog, Enigmol, has demonstrated anticancer activity in numerous in vivo settings. However, as no Enigmol analog with enhanced potency in vitro has been identified, a new strategy to improve efficacy in vivo by increasing tumor uptake was adopted. Herein, synthesis and biological evaluation of two novel fluorinated Enigmol analogs, CF3-Enigmol and CF2-Enigmol, are reported. Each analog was equipotent to Enigmol in vitro, but achieved higher plasma and tissue levels than Enigmol in vivo. Although plasma and tissue exposures were anticipated to trend with fluorine content, CF2-Enigmol absorbed into tissue at strikingly higher concentrations than CF3-Enigmol. Using mouse xenograft models of prostate cancer, we also show that CF3-Enigmol underperformed Enigmol-mediated inhibition of tumor growth and elicited systemic toxicity. By contrast, CF2-Enigmol was not systemically toxic and demonstrated significantly enhanced antitumor activity as compared to Enigmol. PMID- 27190605 TI - Fragment-Based Discovery of a Selective and Cell-Active Benzodiazepinone CBP/EP300 Bromodomain Inhibitor (CPI-637). AB - CBP and EP300 are highly homologous, bromodomain-containing transcription coactivators involved in numerous cellular pathways relevant to oncology. As part of our effort to explore the potential therapeutic implications of selectively targeting bromodomains, we set out to identify a CBP/EP300 bromodomain inhibitor that was potent both in vitro and in cellular target engagement assays and was selective over the other members of the bromodomain family. Reported here is a series of cell-potent and selective probes of the CBP/EP300 bromodomains, derived from the fragment screening hit 4-methyl-1,3,4,5-tetrahydro-2H benzo[b][1,4]diazepin-2-one. PMID- 27190607 TI - Anemia in a neonate with placental mesenchymal dysplasia. AB - Causes of intrauterine fetal death (IUFD) are uncertain in most placental mesenchymal dysplasia (PMD) cases. Our case showed high alpha-fetoprotein levels in the maternal circulation, markedly dilated subchorionic vessels, and neonatal hemoglobin concentration of 8.4 g/dL, suggesting that fetal anemia may explain some adverse outcomes in PMD pregnancies. PMID- 27190608 TI - Cardiac arrest during spinal anesthesia for cervical conization: a case report. AB - Spinal anesthesia is regularly performed worldwide and is an integral part of the modern day anesthesia practice. Although unexpected cardiac arrests during this procedure are very rare, medical professionals should be aware of the potential for this complication. In making the decision to use spinal anesthesia, judicious patient selection, adequate preventive measures, and strict monitoring are important. PMID- 27190609 TI - Intrahepatic and extrahepatic aminotransferase elevation associated with clinical therapeutic events in a schizophrenic patient. AB - A schizophrenic patient showed rhabdomyolysis with idiopathic transaminitis. The intermixed pattern of intrahepatic and extrahepatic alanine aminotransferase (ALT) elevation is associated with respective clinical-therapeutic events. Aminotransferases play a role as surrogate biomarkers of "liver metabolic functioning" beyond the obsolete classical concept associating ALT elevation only with liver cellular damage. PMID- 27190610 TI - Bone formation in subcutaneous pocket after bone flap preservation. AB - Residual periosteum developed periosteal bone formation in the pocket 10 years after cranioplasty, lumpectomy was conducted on the left lower abdomen under local anesthesia. Pathological sections revealed abundant osteocytes and mature bone matrix, and confirmed the bone formation on the residual periosteum. PMID- 27190611 TI - Successful salvage surgery for failed transforaminal lumbosacral interbody fusion using the anterior transperitoneal approach. AB - Transforaminal lumbar interbody fusion (TLIF) is a popular posterior spinal fusion technique, but sometimes require salvage surgery when implant failure occurs, which involves possible neural damage due to postoperative adhesion. The current report deals with successful anterior transperitoneal salvage surgery for failed L5-S TLIF with less neural invasiveness. PMID- 27190612 TI - Spontaneous pneumothorax due to bronchopleural fistula following reirradiation for locoregionally recurrent squamous cell lung cancer. AB - Spontaneous pneumothorax following radiotherapy for pulmonary malignancy is an unusual clinical condition. Here, we report a case of a 78-year-old male suffering from dyspnea during radiotherapy for squamous cell lung cancer of the right main bronchus. Imaging studies and fiberoptic bronchoscopy revealed that pneumothorax was due to a bronchopleural fistula. PMID- 27190613 TI - Imatinib for bleomycin induced pulmonary toxicity: a case report and evidence base review. AB - The evidence supporting therapy with imatinib for bleomycin-induced pneumonitis (BIP) is equivocal. Further experience is needed to establish its role in BIP management. While it may be considered in the management of BIP, it is important to be mindful of the adverse effects including thrombocytopenia and gastrointestinal bleeding. PMID- 27190614 TI - Diabetes insipidus uncovered during conservative management of complicated acute appendicitis. AB - Diabetes insipidus (DI) arises from impaired function of antidiuretic hormone, characterized by hypovolemia, hypernatremia, polyuria, and polydipsia. This case is a reminder of the rare but challenging obstacle that undiagnosed DI poses in fasting surgical patients, requiring prompt recognition and vigilant management of marked homeostatic imbalances. PMID- 27190615 TI - Teratodermoid mimicking cholecystitis. AB - An acute abdomen assessment in pregnancy is complicated. Pain can have obstetric and nonobstetric causes. Cholecystitis is a common cause of pain in pregnancy with significant morbidity if not managed promptly. We report a case of a ruptured, torted, right ovarian teratodermoid erroneously diagnosed as cholecystitis in pregnancy. PMID- 27190617 TI - The first genetically confirmed Japanese patient with mucolipidosis type IV. AB - Mucolipidosis type IV (MLIV) is a rare neurodegenerative disorder characterized by severe psychomotor delay and visual impairment. We report the brain pathology in the first Japanese patient of MLIV with a novel homozygous missense mutation in MCOLN1. We detected the localized increase in p62-reactive astrocytes in the basal ganglia. PMID- 27190616 TI - Asenapine augmentation in bipolar disorders: a case series. AB - Asenapine, a novel second-generation antipsychotic is effective in acute treatment of bipolar I disorder patients in combination with mood stabilizers even in resistant cases. Although there is no evidence for asenapine's efficacy to be superior to currently available agents, asenapine's favorable weight and metabolic profile are of clinical interest. PMID- 27190618 TI - A review of the role of anticoagulation for patients with infective endocarditis and embolic stroke. AB - Stroke is a common embolic complication of infective endocarditis. The most important treatment to prevent stroke in endocarditis is the initiation of antibiotic therapy. It is unclear whether the initiation of de novo anticoagulation (i.e, warfarin) in patients with infective endocarditis is beneficial, since there are no large or randomized controlled trials in this area. However, this case report suggests, despite the limited evidence, that anticoagulation in this patient caused no harm and could suggest a hint of possible benefit. PMID- 27190619 TI - A child with mastocytosis and lymphomatoid papulosis. AB - A change in clinical behavior of a disease should prompt search for differential diagnoses. Here, the appearance of ulcerated skin nodules in a preexisting cutaneous mastocytosis revealed a concurrent lymphomatoid papulosis - a CD30+ lymphoproliferative skin disease with histological features of a malignant lymphoma, but with a benign self-healing course. PMID- 27190620 TI - Diagnosis of desmoplastic small-round-cell tumor by cytogenetic analysis: a case report. AB - We herein present atypical histologic and immunohistochemical features of DSRCT. The various differential diagnoses of DSRCT may occasionally generate confusion. Cytogenetic analysis may solve diagnostic dilemmas such as that in our case. Further studies are required to establish a standard treatment for DSRCT. PMID- 27190622 TI - An unusual case of lingual tonsillar hypertrophy. AB - Lingual tonsillar hypertrophy is an unusual presentation of voice change. If managed incorrectly this group of patients has the potential to deteriorate significantly causing airway obstruction and potentially death. PMID- 27190621 TI - Surgical management of a splenic artery aneurysm. AB - Aneurisms of the splenic artery are rare clinical findings. Surgeons and interventional radiologists should co-operate in the management of this challenging disease; we describe here a surgical option. PMID- 27190623 TI - Multiple nodular lesions following Pneumocystis pneumonia in a non-HIV immunocompromised patient. AB - Cytomegalovirus superinfection is associated with a poor prognosis in non-HIV Pneumocystis pneumonia (PCP) and can cause deterioration of PCP not only simultaneously but also after initiating PCP treatment. Cytomegalovirus pneumonia should be considered in cases with deterioration after initiating PCP treatment; multiple nodular lesions are useful findings for the diagnosis. PMID- 27190624 TI - Giant diverticulum- A rare complication of a common surgical condition. AB - A gentleman presented with abdominal distension and pain. CT confirmed a 20 cm sigmoid diverticulum. A giant diverticulum, typified by diverticula greater than 4 cm, often requires colonic resection. Fewer than 200 cases have been reported, most measuring 7-15 cm. I present a rare complication of a common surgical condition with images. PMID- 27190625 TI - Doctor, I am sweating on just one side of my body: unilateral hyperhidrosis associated with mesothelioma. AB - Unilateral hyperhidrosis is rare and should prompt a thorough review for potentially serious underlying etiologies. Available treatments for unilateral hyperhidrosis secondary to mesothelioma are limited and its presence as a symptom usually signifies advanced disease and a poor prognosis. PMID- 27190626 TI - A dangerous loop. AB - A 76-year-old man developed a hemoperitoneum after ERCP for choledocholithiasis. He underwent a laparotomy and splenectomy for a capsular tear at the splenic hilum, a rare complication of ERCP. "Bowing" of the endoscope with torsion on the greater curvature of the stomach may lead to shear forces causing splenic injury. PMID- 27190627 TI - Glimpse into the future: harnessing autophagy to promote anti-tumor immunity with the DRibbles vaccine. AB - Because the benefits of immune checkpoint blockade may be restricted to tumors with pre-existing immune recognition, novel therapies that facilitate de novo immune activation are needed. DRibbles is a novel multi-valent vaccine that is created by disrupting degradation of intracellular proteins by the ubiquitin proteasome system. The DRibbles vaccine is comprised of autophagosome vesicles that are enriched with defective ribosomal products and short-lived proteins, known tumor-associated antigens, mediators of innate immunity, and surface markers that encourage phagocytosis and cross-presentation by antigen presenting cells. Here we summarize the rationale and preclinical development of DRibbles, translational evidence in support of DRibbles as a therapeutic strategy in humans, as well as recent developments and expected future directions of the DRibbles vaccine in the clinic. PMID- 27190628 TI - Concurrent SPECT/PET-CT imaging as a method for tracking adoptively transferred T cells in vivo. AB - BACKGROUND: The ability of T-cells to traffic to and penetrate tumors impacts the clinical efficacy of T-cell therapy therefore methods to track transferred T cells in vivo are needed. In this preliminary report, we evaluated the use of concurrent SPECT/PET-CT imaging to monitor the egress of HER-2/neu specific T cells in a breast cancer patient with extensive bone-only metastatic disease. FINDINGS: Indium (In-111) labeled T-cells demonstrated similar or greater viability than unlabeled T-cells at either a low or high dose of In-111 over a 24 h incubation period in vitro. The function of labeled or unlabeled T-cells was not significantly different (p > 0.05) at either dose. T-cells trafficked to all sites of metastatic disease and infiltrated the tumor as assessed by SPECT imaging. In-111 uptake at 24 h after infusion varied from 3.8 (right proximal humerus) to 6.3 (right sacrum) background corrected counts per pixel and remained elevated at 48 h. Concurrent PET-CT imaging demonstrated a fluorodeoxyglucose flare, measured by increase in tumor site uptake as high as 32 % and at most sites of disease at 48 h. This flare was associated with focal pain after T-cell infusion at metastatic sites. The patient had stable disease for 18 months after completion of T-cell therapy. CONCLUSION: Concurrent SPECT/PET-CT imaging, over a 48-h period after T-cell infusion, provided evidence of T-cell homing to all disease sites as well as a tumor metabolism flare response. This technique may be useful for monitoring T-cell trafficking after autologous as well as chimeric antigen receptor T-cell infusion. TRIAL REGISTRAION: Trial registered at ClinicalTrials.gov registration number NCT00791037, registered 13 November 2008. PMID- 27190630 TI - Can abscopal effects of local radiotherapy be predicted by modeling T cell trafficking? AB - The abscopal effect of radiation describes tumor regression in metastases outside of the field upon treatment of one site, and is mediated by radiation-induced anti-tumor T cells. The ability of radiation to generate an in situ tumor vaccine and improve responses to immunotherapy is under intense investigation in the clinic. Preclinical and clinical evidence shows that multiple factors regulate radiation interaction with the immune system within and outside of the irradiated tumor. Poleszczuk and colleagues developed a mathematical model of T cell trafficking between metastases, and in a recent publication propose that the specific metastatic site irradiated determines the ability of T cells to traffic to other metastases and mediate abscopal responses and should dictate clinical decision making [Poleszczuk et al. Cancer Res 76:1009-18, 2016]. Here we critically discuss this model in light of the currently available information about abscopal responses in mice and patients. Caution in relying upon overly simplified models, before validation in real patients, is recommended. PMID- 27190629 TI - Agonist anti-GITR monoclonal antibody and stereotactic radiation induce immune mediated survival advantage in murine intracranial glioma. AB - BACKGROUND: Glioblastoma (GBM) is a poorly immunogenic neoplasm treated with focused radiation. Immunotherapy has demonstrated synergistic survival effects with stereotactic radiosurgery (SRS) in murine GBM. GITR is a co-stimulatory molecule expressed constitutively on regulatory T-cells and by effector T-cells upon activation. We tested the hypothesis that anti-GITR monoclonal antibody (mAb) and SRS together would confer an immune-mediated survival benefit in glioma using the orthotopic GL261 glioma model. METHODS: Mice received SRS and anti-GITR 10 days after implantation. The anti-GITR mAbs tested were formatted as mouse IgG1 D265A (anti-GITR (1)) and IgG2a (anti-GITR (2a)) isotypes. Mice were randomized to four treatment groups: (1) control; (2) SRS; (3) anti-GITR; (4) anti-GITR/SRS. SRS was delivered to the tumor in one fraction, and mice were treated with mAb thrice. Mice were euthanized on day 21 to analyze the immunologic profile of tumor, spleen, and tumor draining lymph nodes. RESULTS: Anti-GITR (1)/SRS significantly improved survival over either treatment alone (p < .0001) with a cure rate of 24 % versus 0 % in a T-lymphocyte-dependent manner. There was elevated intratumoral CD4+ effector cell infiltration relative to Treg infiltration in mice treated with anti-GITR (1)/SRS, as well as significantly elevated IFNgamma and IL-2 production by CD4+ T-cells and elevated IFNgamma and TNFalpha production by CD8+ T-cells. There was increased mRNA expression of M1 markers and decreased expression of M2 markers in tumor infiltrating mononuclear cells. The anti-GITR (2a)/SRS combination did not improve survival, induce tumor regression, or result in Treg depletion. CONCLUSIONS: These findings provide preclinical evidence for the use of anti-GITR (1) non-depleting antibodies in combination with SRS in GBM. PMID- 27190631 TI - The MUK five protocol: a phase II randomised, controlled, parallel group, multi centre trial of carfilzomib, cyclophosphamide and dexamethasone (CCD) vs. cyclophosphamide, bortezomib (Velcade) and dexamethasone (CVD) for first relapse and primary refractory multiple myeloma. AB - BACKGROUND: Multiple myeloma is a plasma cell tumour with an annual incidence in the UK of approximately 40-50 per million i.e. about 4500 new cases per annum. The triple combination cyclophosphamide, bortezomib (Velcade(r)) and dexamethasone (CVD) is an effective regimen at relapse and has emerged in recent years as the standard therapy at first relapse in the UK. Carfilzomib has good activity as a single agent in the relapsed setting, and it is expected that efficacy will be improved when used in combination with dexamethasone and cyclophosphamide. METHODS: MUK Five is a phase II open label, randomised, controlled, parallel group, multi-centre trial that will compare the activity of carfilzomib, cyclophosphamide and dexamethasone (CCD) with that of CVD, given over an equivalent treatment period (24 weeks), in participants with multiple myeloma at first relapse, or refractory to no more than 1 line of treatment. In addition, the study also aims to assess the utility of a maintenance schedule of carfilzomib in these participants. The primary objective of the trial is to assess whether CCD provides non-inferior activity in terms of >= VGPR rates at 24 weeks, and whether the addition of maintenance treatment with carfilzomib to CCD provides superior activity in terms of progression-free survival, as compared to CCD with no maintenance. Secondary objectives include comparing toxicity profiles, further summarizing and comparing the activity of the different treatment arms and analysis of the effect of each treatment arm on minimal residual disease status. DISCUSSION: The development of carfilzomib offers the opportunity to further explore the anti-tumour efficacy of proteasome inhibition and, based on the available evidence, it is important and timely to obtain data on the activity, toxicity and tolerability of this drug. In contrast to ongoing phase III trials, this phase II trial has a unique subset of participants diagnosed with multiple myeloma at first relapse or refractory to no more than 1 line of treatment and will also evaluate the utility of maintenance with carfilzomib for up to 18 months and investigate minimal residual disease status to provide information on depth of response and the prognostic impact thereof. TRIAL REGISTRATION: The trial is registered under ISRCTN17354232, December 2012. PMID- 27190632 TI - The pharmacokinetics of mianserin suppositories for rectal administration in dogs and healthy volunteers: a pilot study. AB - BACKGROUND: We formulated mianserin suppositories for the treatment of delirium and evaluated their pharmacokinetics by measuring plasma drug concentrations in dogs and healthy human volunteers. METHODS: Mianserin suppositories were prepared by a melting technique using Tetramide(r) tablets and Witepsol H-15 as the suppository base. Pharmacokinetics of this 30-mg mianserin preparation were evaluated in three beagle dogs and three healthy adult males, in line with ethics committee approval. Plasma mianserin levels were determined using gas chromatography-mass spectrometry. RESULTS: In dogs, the maximum plasma mianserin concentration (Cmax) was 1.3 +/- 0.4 ng/mL, the time to Cmax (tmax) was 5.5 +/- 4.3 h, and the area under the plasma concentration-time curve from 0 to 24 h (AUC0-24) was 18.9 +/- 1.9 h?ng/mL. In humans, the Cmax was 14.6 +/- 6.3 ng/mL, the tmax was 8 h, and the AUC0-24 was 266 +/- 103 h?ng/mL. CONCLUSIONS: The current study characterized the pharmacokinetics of mianserin suppositories in dogs and humans. As compared to oral administration, the suppositories produced a lower Cmax and a delayed tmax, although AUC0-24 values were comparable. It will be necessary to identify an appropriate dose that produces an adequate plasma mianserin concentration for effective and safe clinical use. TRIAL REGISTRATION: UMIN000013853. PMID- 27190633 TI - Clinical assessment of hypertension in children. AB - The use of blood pressure measurements have become a routine part of physical exam for the evacuation of cardiovascular health adults and, more recently, children. The most widely used definition of hypertension is delineate as greater than 90 % BP according to age, sex, and height by the National High Blood Pressure Education Program. Current research suggests that pediatric hypertension is influenced by multitude of factors including birth weight, maturity during birth, heredity, and diet leading to primary hypertension. Factors influencing secondary hypertension include renal abnormalities, coarctation of the aorta, medications, neoplasm, etc. The treatment for pediatric hypertension is carried out with diet and exercise as the first line of defense. Only under non compliance with diet and exercise is pharmaceutical intervention appropriate. This paper outlines a concise summary of the current understanding and research for scientists, clinicians, as well as for the general population to better understand pediatric hypertension. PMID- 27190634 TI - Neobenedenia melleni Parasite of Red Snapper, Lutjanus erythropterus, with Regression Statistical Analysis between Fish Length, Temperature, and Parasitic Intensity in Infected Fish, Cultured at Jerejak Island, Penang, Malaysia. AB - The fish parasites collected from Lutjanus erythropterus fish species showed a correlation with parasitic intensity, fish size, and temperature, and statistical model summary was produced using SPSS version 20, statistical software. Statistical model summary concluded that among the variables which significantly predict the prevalence of Neobenedenia melleni parasites are fish length and water temperature, both significant at 1% and 5%. Furthermore, the increase in one unit of fish length, holding other variables constant, increases the prevalence of parasite by approximately 1 (0.7~1) unit. Also, increasing the temperature from 32 degrees C to 33 degrees C will positively increase the number of parasites by approximately 0.32 units, holding other variables constant. The model can be summarized as estimated number of Neobenedenia melleni parasites = 8.2 + 0.7 * (fish length) + 0.32 * (water temperature). Next, this study has also shown the DNA sequence and parasitic morphology of Neobenedenia melleni. Nucleotide sequence for 18s ribosomal gene RNA in this study showed 99% similarity with N. melleni EU707804.1 from GenBank. Finally, all the sequence of Neobenedenia melleni in this study was deposited in GenBank with accession numbers of KU843501, KU843502, KU843503, and KU843504. PMID- 27190635 TI - Two-Dimensional Cutting (TDC) Vitrectome: In Vitro Flow Assessment and Prospective Clinical Study Evaluating Core Vitrectomy Efficiency versus Standard Vitrectome. AB - Purpose. To evaluate comparative aspiration flow performance and also vitrectomy operating time efficiency using a double-cutting open port vitreous cutting system incorporated in a two-dimensional cutting (TDC, DORC International) vitrectome design versus standard vitreous cutter. Methods. In vitro investigations compared aspiration flow rates in artificial vitreous humor at varying cutter speeds and vacuum levels using a TDC vitrectome and a standard vitrectome across different aspiration pump systems. A prospective single-centre clinical study evaluated duration of core vitrectomy in 80 patients with macular pucker undergoing 25-gauge or 27-gauge vitrectomy using either a TDC vitrectome at 16,000 cuts per minute (cpm) or standard single-cut vitrectome, combined with a Valve Timing intelligence (VTi) pump system (EVA, DORC International). Results. Aspiration flow rates remained constant independent of TDC vitrectome cut rate, while flow rates decreased linearly at higher cutter speeds using a classic single-blade vitrectome. Mean duration of core vitrectomy surgeries using a TDC vitreous cutter system was significantly (p < 0.001) shorter than the mean duration of core vitrectomy procedures using a single-cut vitrectome of the same diameter (reduction range, 34%-50%). Conclusion. Vitrectomy surgery performed using a TDC vitrectome was faster than core vitrectomy utilizing a standard single-action vitrectome at similar cut speeds. PMID- 27190636 TI - Automatic Screening and Grading of Age-Related Macular Degeneration from Texture Analysis of Fundus Images. AB - Age-related macular degeneration (AMD) is a disease which causes visual deficiency and irreversible blindness to the elderly. In this paper, an automatic classification method for AMD is proposed to perform robust and reproducible assessments in a telemedicine context. First, a study was carried out to highlight the most relevant features for AMD characterization based on texture, color, and visual context in fundus images. A support vector machine and a random forest were used to classify images according to the different AMD stages following the AREDS protocol and to evaluate the features' relevance. Experiments were conducted on a database of 279 fundus images coming from a telemedicine platform. The results demonstrate that local binary patterns in multiresolution are the most relevant for AMD classification, regardless of the classifier used. Depending on the classification task, our method achieves promising performances with areas under the ROC curve between 0.739 and 0.874 for screening and between 0.469 and 0.685 for grading. Moreover, the proposed automatic AMD classification system is robust with respect to image quality. PMID- 27190637 TI - Multimodal Image Analysis in Acquired Vitelliform Lesions and Adult-Onset Foveomacular Vitelliform Dystrophy. AB - Purpose. To characterize vitelliform lesions (VLs) in adult-onset foveomacular vitelliform dystrophy (AOFVD) and acquired vitelliform (AVL) patients using multimodal image analysis. Methods. Retrospective study of twenty-eight eyes from nineteen patients diagnosed with AVL or AOFVD. They were evaluated by color fundus photographs, fundus autofluorescence (FAF), fluorescein angiography (FA), and spectral-domain optical coherence tomography (SD-OCT). Results. Bilateral VLs were associated with AOFVD (p = 0.013). Regular and centered VLs were associated with AOFVD (p = 0.004 and p = 0.016), whereas irregular and noncentered lesions were more frequent in AVL patients. Visual acuity, greatest linear dimension (GLD), lesion height (LH), and pseudohypopyon were similar between groups. Whereas median LH and GLD in AVL group diminished significantly during follow-up (p = 0.009 and p = 0.001), AOFVD lesions tended to become larger and thicker. Conclusions. When consulting a patient presenting a VL with unknown age of onset, familial history, or previous retinal diseases, some aspects of multimodal imaging assessment may lead the ophthalmologist to a correct diagnosis. PMID- 27190638 TI - Hyaluronate Acid-Dependent Protection and Enhanced Corneal Wound Healing against Oxidative Damage in Corneal Epithelial Cells. AB - Purpose. To evaluate the effects and mechanism of exogenous hyaluronate (HA) in promoting corneal wound healing. Methods. Human corneal epithelial cells (HCECs) were incubated with different concentrations of HA to evaluate their efficiency in promoting cell migration and their modulation of repair factors. After inducing hyperosmolar conditions, the cell morphologies, cell apoptosis, and expression levels of TNF-alpha and MMP-9 were detected to assess the protective role of HA. Corneal epithelium-injured rat models were established to test the therapeutic effects of 0.3% HA. Then, the wound healing rates, the RNA expression levels of inflammatory cytokines, and repair factors were examined. Results. HCECs in the 0.03% and 0.3% HA groups showed fewer morphological alterations and lower rates of cell apoptosis following preincubation with HA under hyperosmolar conditions, as well as the expression levels of MMP-9 and TNF-alpha. In the rat model, the areas of fluorescein staining in the corneas of 0.3% HA group were significantly smaller than the control group. The expression levels of IL-1beta and MMP-9 were decreased, while CD44 and FN were increased in the 0.3% HA group. Conclusion. HA enhanced corneal epithelial cell wound healing by promoting cell migration, upregulating repair responses, and suppressing inflammatory responses. PMID- 27190639 TI - Repeatability and Reproducibility of Noninvasive Keratograph 5M Measurements in Patients with Dry Eye Disease. AB - Purpose. To determine the intraexaminer repeatability and interexaminer reproducibility of tear meniscus height (TMH) and noninvasive Keratograph tear breakup time (NIKBUT) measurements obtained with the Keratograph 5M (K5M) in a sample of healthy and dry eye populations. Methods. Forty-two patients with dry eye disease (DED group) and 42 healthy subjects (healthy group) were recruited in this prospective study. In all subjects, each eye received 3 consecutive measurements using the K5M for the TMH and NIKBUTs (NIKBUT-first and NIKBUT average). And then a different examiner repeated the measurements. The repeatability and reproducibility of measurements were assessed by the coefficient of variation (CV) and intraclass correlation coefficient (ICC). Results. The repeatability and reproducibility of TMH and NIKBUTs were good in both DED and healthy groups (CV% <= 26.1% and ICC >= 0.75 for all measurements). Patients with DED showed better intraexaminer repeatability for NIKBUTs, but worse for TMH than healthy subjects. Average TMH, NIKBUT-first, and NIKBUT average were significantly lower in DED group than in healthy group (all P values < 0.05). Conclusions. Measurements of TMH and NIKBUTs obtained with the K5M may provide a simple, noninvasive screening test for dry eye with acceptable repeatability and reproducibility. The NIKBUTs were more reliable, but TMH was less reliable in patients with DED. PMID- 27190640 TI - Comparison of the Efficacy of Intravitreal Aflibercept and Bevacizumab for Macular Edema Secondary to Branch Retinal Vein Occlusion. AB - Fifty-two eyes of 52 patients with treatment-naive macular edema associated with perfused branch retinal vein occlusion were retrospectively reviewed. Twenty seven cases received PRN intravitreal bevacizumab, and 25 cases were treated by PRN intravitreal aflibercept with monthly follow-ups for 12 months. Both aflibercept and bevacizumab were effective in reduction of macular thickness and improvement of visual acuity for the participants. Both antivascular endothelial growth factor agents had similar efficacy and duration of treatment for these eyes with macular edema secondary to branch retinal vein occlusion during a 12 month period. No serious systemic or ocular adverse events were reported. PMID- 27190641 TI - Relationship between Altered Platelet Morphological Parameters and Retinopathy in Patients with Type 2 Diabetes Mellitus. AB - Purpose. To investigate whether platelet morphology or function is altered in patients with diabetic retinopathy (DR). Methods. This prospective study enrolled 85 healthy controls (HCs) (group 1) and 262 patients with Type 2 diabetes mellitus (T2DM). Patients were subclassified into three groups according to ocular findings: no DR (group 2; n = 88); nonproliferative DR (group 3; n = 88), and proliferative DR (group 4; n = 86). Mean platelet volume (MPV), platelet distribution width (PDW), platelet large cell ratio (PLCR), plateletcrit (PCT) values, and platelet count were measured in the studied groups. Results. MPV, PDW, and PLCR levels were significantly altered in groups 2-4 compared with HCs (p < 0.05, p < 0.05, p < 0.05). Compared with group 2, both DR groups had higher MPV and PDW levels, with a significant difference between groups 2 and 4 for both MPV (p = 0.036) and PDW (p = 0.006). PLCR correlated with retinopathy stage, but no significant difference was found between the DR groups. Platelet count and PCT values were not significantly different between the groups (p > 0.05). Conclusion. Our findings suggest an association between mean platelet indices (MPI) (i.e., MPV, PDW, and PLCR) and DR stage. Therefore, MPI could be a beneficial prognostic marker of DR in patients with T2DM. PMID- 27190642 TI - Long-Term Observation of Triplex Surgery for Cataract after Phakic 6H Implantation for Super High Myopia. AB - Purpose. To analyze the safety, effectiveness, and stability of triplex surgery for phakic 6H anterior chamber phakic intraocular lens explantation and phacoemulsification with in-the-bag IOL implantation for super high myopia in long-term observations. Methods. This retrospective case series evaluated 16 eyes of 10 patients who underwent triplex surgery. Best corrected visual acuity (BCVA), endothelial cell density (ECD), and associated adverse events were evaluated. Results. The mean follow-up time after the triplex surgery was 46 +/- 14 months. The mean logMAR BCVA was significantly improved after triplex surgery (P = 0.047). One eye developed endophthalmitis five days postoperatively and underwent pars plana vitrectomy (PPV). Five eyes with preoperative severe endothelial cell loss developed corneal decompensation and underwent keratoplasty at a mean time of 9.4 +/- 2.6 months after the triplex surgery. One eye had graft failure and underwent a second keratoplasty. The eye developed rhegmatogenous retinal detachment and underwent PPV with silicone oil 18 months later. ECD before the triplex surgery was not significantly different compared with that at last follow-up (P = 0.495) apart from these five eyes. Three eyes (18.8%) developed posterior capsule opacification. Conclusions. Triplex surgery was safe and effective for phakic 6H related complicated cataracts. Early extraction before severe ECD loss is recommended. PMID- 27190643 TI - Evaluation of Antidiabetic and Antihyperlipidemic Effects of Peganum harmala Seeds in Diabetic Rats. AB - The present study was carried out to investigate the antidiabetic and antihyperlipidemic properties of hydroalcoholic extract of Peganum harmala in streptozotocin-induced diabetic male rats. In an experimental study, 64 normal Wistar albino male rats (200-230 g) were randomly divided into 8 groups. Control and diabetic rats were treated with normal saline and three different doses (30, 60, and 120 mg/kg) of hydroalcoholic extract of Peganum harmala seeds for 4 weeks orally. At the end of treatment, blood samples were taken and glucose, triglycerides, total cholesterol, LDL-c, HDL-c, malondialdehyde (MDA), total antioxidant capacity (TCA), ALT, AST, GGT, bilirubin, and glycosylated hemoglobin (HbA1C) were determined. STZ-induced diabetic rats showed significant changes in the values of glucose, triglycerides, total cholesterol, LDL-c, MDA, TAC, ALT, AST, GGT, bilirubin, and HbA1C in comparison with normal rats. Administration of the extract to diabetic rats resulted in a remarkable decrease in glucose, lipid profiles, MDA, ALT, AST, GGT, bilirubin, and HbA1C levels and increase in TAC relative to diabetic group. The results of this study indicated that hydroalcoholic extract of Peganum harmala seeds possesses antidiabetic and hypolipidemic activities and could be useful in treatment of diabetes. PMID- 27190644 TI - Liposarcoma of the Spermatic Cord: Impact of Final Surgical Intervention--An Institutional Experience. AB - BACKGROUND: Paratesticular liposarcomas are almost always mistakenly diagnosed as inguinal hernias subsequently followed by inadequate operation. METHODS: 14 consecutive patients with paratesticular liposarcoma were retrospectively reviewed. Preoperative management was evaluated. Disease-free and overall survival were determined. RESULTS: In 11 patients primary and in 3 patients recurrent liposarcoma of the spermatic cord were diagnosed. Regarding primary treatment in primary surgical intervention resection was radical (R0) in 7 of 14 (50%) patients, marginal (R1) in 6 (43%) patients, and incomplete with macroscopic residual tumour (R2) in 1 (7%) patient. Primary treatment secondary surgical intervention was performed in 4 patients: resection was radical (R0) in 3 (75%) patients and marginal (R1) in 1 (25%) patient. Regarding secondary treatment in recurrent disease resection was marginal (R1) in 3 patients (100%). Final histologic margins were negative in 10 patients with primary disease (71%) and positive in 4 patients with subsequent recurrent disease. After radical resection disease-free survival rates at 3 years were 100%. Overall survival at 4.5 years (54 (18-180) months) was 64%. CONCLUSION: An incomplete first surgical step increases the number of positive margins leading to local recurrences and adverse prognoses. Aggressive surgery should be attempted to attain 3-dimensional negative margins. PMID- 27190645 TI - Does Acellular Dermal Matrix Thickness Affect Complication Rate in Tissue Expander Based Breast Reconstruction? AB - Background. While the benefits of using acellular dermal matrices (ADMs) in breast reconstruction are well described, their use has been associated with additional complications. The purpose of this study was to determine if ADM thickness affects complications in breast reconstruction. Methods. A retrospective chart review was performed including all tissue expander based breast reconstructions with AlloDerm (LifeCell, Branchburg, NJ) over 4 years. We evaluated preoperative characteristics and assessed postoperative complications including seroma, hematoma, infection, skin necrosis, and need for reintervention. We reviewed ADM thickness and time to Jackson-Pratt (JP) drain removal. Results. Fifty-five patients underwent 77 ADM-associated tissue expander based breast reconstructions, with average age of 48.1 years and average BMI of 25.9. Average ADM thickness was 1.21 mm. We found higher complication rates in the thick ADM group. Significant associations were found between smokers and skin necrosis (p < 0.0001) and seroma and prolonged JP drainage (p = 0.0004); radiated reconstructed breasts were more likely to suffer infections (p = 0.0085), and elevated BMI is a significant predictor for increased infection rate (p = 0.0037). Conclusion. We found a trend toward increased complication rates with thicker ADMs. In the future, larger prospective studies evaluating thickness may provide more information. PMID- 27190646 TI - Hematological and Biochemistry Profile and Risk Factors Associated with Pulmonary Tuberculosis Patients in Guyana. AB - Objective. To evaluate the hematological and biochemistry profile of patients with or without HIV-TB at the Georgetown Chest Clinic, Guyana. Methods. An observational, laboratory based study was designed to assess the relationship of PTB and HIV with patients routine biochemical and hematological values. The study was conducted during the period January 2013 to December 2014; a total sample size of 316 patients was enrolled following exclusion and inclusion criteria. Results. Mean age of study population was 40.1 +/- 13.8 (95% CI 38.6-41.7) and most were between 40 and 49 age group (27.8%, 95% CI 23.2-33.0). More males were in the study 74.4% (95% CI 69.3-78.8) than females 81% (95% CI 21.1-30.7). 30% (95% CI 25.3-35.3) had a sputum smear grade of 3+ and 62.5% (95% CI 47.0-75.7) showed a CD4 count <200. The study demonstrated significantly low hemoglobin (Hb) 91.7% (95% CI 78.2-97.1), low WBC 27.8% (95% CI 15.8-44.0), high indirect bilirubin 7.4% (95% CI 2.1-23.3), ALT 41.8% (95% CI 28.4-56.7), and AST 72.2% (95% CI 57.3-83.3) among TB-HIV patients. Homelessness RR (relative risk) 2.2 (95% CI 0.48-12.3), smoking RR 1.09 (95% CI 1.01-1.19), and gender (male) RR 1.2 (95% CI 0.61-2.26) were main associated risk factors. Conclusions. There is slight variation among PTB and PTB-HIV coinfected patients in some hematological and biochemistry parameters. PMID- 27190647 TI - Preoperative Quantitative MR Tractography Compared with Visual Tract Evaluation in Patients with Neuropathologically Confirmed Gliomas Grades II and III: A Prospective Cohort Study. AB - Background and Purpose. Low-grade gliomas show infiltrative growth in white matter tracts. Diffusion tensor tractography can noninvasively assess white matter tracts. The aim was to preoperatively assess tumor growth in white matter tracts using quantitative MR tractography (3T). The hypothesis was that suspected infiltrated tracts would have altered diffusional properties in infiltrated tract segments compared to noninfiltrated tracts. Materials and Methods. Forty-eight patients with suspected low-grade glioma were included after written informed consent and underwent preoperative diffusion tensor imaging in this prospective review-board approved study. Major white matter tracts in both hemispheres were tracked, segmented, and visually assessed for tumor involvement in thirty-four patients with gliomas grade II or III (astrocytomas or oligodendrogliomas) on postoperative neuropathological evaluation. Relative fractional anisotropy (rFA) and mean diffusivity (rMD) in tract segments were calculated and compared with visual evaluation and neuropathological diagnosis. Results. Tract segment infiltration on visual evaluation was associated with a lower rFA and high rMD in a majority of evaluated tract segments (89% and 78%, resp.). Grade II and grade III gliomas had similar infiltrating behavior. Conclusion. Quantitative MR tractography corresponds to visual evaluation of suspected tract infiltration. It may be useful for an objective preoperative evaluation of tract segment involvement. PMID- 27190648 TI - Towards Tailored Patient's Management Approach: Integrating the Modified 2010 ACR Criteria for Fibromyalgia in Multidimensional Patient Reported Outcome Measures Questionnaire. AB - Objectives. To assess the validity, reliability, and responsiveness to change of a patient self-reported questionnaire combining the Widespread Pain Index and the Symptom Severity Score as well as construct outcome measures and comorbidities assessment in fibromyalgia patients. Methods. The PROMs-FM was conceptualized based on frameworks used by the WHO Quality of Life tool and the PROMIS. Initially, cognitive interviews were conducted to identify item pool of questions. Item selection and reduction were achieved based on patients as well as an interdisciplinary group of specialists. Rasch and internal consistency reliability analyses were implemented. The questionnaire included the modified ACR criteria main items (Symptom Severity Score and Widespread Pain Index), in addition to assessment of functional disability, quality of life (QoL), review of the systems, and comorbidities. Every patient completed HAQ and EQ-5D questionnaires. Results. A total of 146 fibromyalgia patients completed the questionnaire. The PROMs-FM questionnaire was reliable as demonstrated by a high standardized alpha (0.886-0.982). Content construct assessment of the functional disability and QoL revealed significant correlation (p < 0.01) with both HAQ and EQ-5D. Changes in functional disability and QoL showed significant (p < 0.01) variation with diseases activity status in response to therapy. There was higher prevalence of autonomic symptoms, CVS risk, sexual dysfunction, and falling. Conclusions. The developed PROMs-FM questionnaire is a reliable and valid instrument for assessment of fibromyalgia patients. A phased treatment regimen depending on the severity of FMS as well as preferences and comorbidities of the patient is the best approach to tailored patient management. PMID- 27190649 TI - Purification and Characterization of a Novel Intracellular Sucrase Enzyme of Leishmania donovani Promastigotes. AB - The promastigote stage of Leishmania resides in the sand fly gut, enriched with sugar molecules. Recently we reported that Leishmania donovani possesses a sucrose uptake system and a stable pool of intracellular sucrose metabolizing enzyme. In the present study, we purified the intracellular sucrase nearly to its homogeneity and compared it with the purified extracellular sucrase. The estimated size of intracellular sucrase is ~112 kDa by gel filtration chromatography, native PAGE, and substrate staining. However, in SDS-PAGE, the protein is resolved at ~56 kDa, indicating the possibility of a homodimer in its native state. The kinetics of purified intracellular sucrase shows its higher substrate affinity with a K m of 1.61 mM than the extracellular form having a K m of 4.4 mM. The highly specific activity of intracellular sucrase towards sucrose is optimal at pH 6.0 and at 30 degrees C. In this report the purification and characterization of intracellular sucrase provide evidence that sucrase enzyme exists at least in two different forms in Leishmania donovani promastigotes. This intracellular sucrase may support further intracellular utilization of transported sucrose. PMID- 27190650 TI - Repeated Exposure to Dissection Does Not Influence Students' Attitudes towards Human Body Donation for Anatomy Teaching. AB - The use of unclaimed bodies for anatomical dissection has been the main method of instruction at our institution. There is however a shortage of cadavers for dissection given the increase in the number of medical schools as well as in the number of students enrolling in these schools. This shortage could be mitigated by having voluntary human body donation programs. This study aimed at assessing the attitudes of medical students and surgical residents towards body donation for anatomy learning. We conducted an online survey involving 72 first-year medical students and 41 surgical residents at University of Nairobi who had completed one year of anatomy dissection. For the medical students, this was their first dissection experience while it was the second exposure for the surgery trainees. Most of the surgical trainees (70.7%) and medical students (68.1%) were opposed to self-body donation. This was mainly due to cultural (37%) and religious (20%) barriers. Surprisingly, of those not willing to donate themselves, 67.9% (82.8% surgical trainees, 59.2% medical students) would recommend the practice to other people. Exposure to repeated dissection does not change the perceptions towards body donation. It is noteworthy that culture and religion rank high as clear barriers amongst this "highly informed" group of potential donors. PMID- 27190652 TI - SOD1 Gene +35A/C (exon3/intron3) Polymorphism in Type 2 Diabetes Mellitus among South Indian Population. AB - Superoxide dismutase is an antioxidant enzyme that is involved in defence mechanisms against oxidative stress. Cu/Zn SOD is a variant that is located in exon3/intron3 boundary. The aim of the present study was to investigate whether the Cu/Zn SOD (+35A/C) gene polymorphism is associated with the susceptibility to type 2 diabetes mellitus among south Indian population. The study included patients with type 2 diabetes mellitus (n = 100) and healthy controls (n = 75). DNA was isolated from the blood and genotyping of Cu/Zn SOD gene polymorphism was done by polymerase chain reaction based restriction fragment length polymorphism method. Occurrence of different genotypes and normal (A) and mutant (C) allele frequencies were determined. The frequency of the three genotypes of the total subjects was as follows: homozygous wild-type A/A (95%), heterozygous genotype A/C (3%), and homozygous mutant C/C (2%). The mutant (C) allele and the mutant genotypes (AC/CC) were found to be completely absent among the patients with type 2 diabetes mellitus. Absence of mutant genotype (CC) shows that the Cu/Zn SOD gene polymorphism may not be associated with the susceptibility to type 2 diabetes mellitus among south Indian population. PMID- 27190651 TI - Poly(lactic-co-glycolic) Acid-Chitosan Dual Loaded Nanoparticles for Antiretroviral Nanoformulations. AB - Poly(lactic-co-glycolic acid) (PLGA) chitosan (CS) coated nanoparticles (NPs) were loaded with two antiretrovirals (ARVs) either lamivudine (LMV) which is hydrophilic or nevirapine (NVP) which is hydrophobic or both LMV and NVP. These ARVs are of importance in resource-limited settings, where they are commonly used in human immunodeficiency virus (HIV-1) treatment due to affordability and accessibility. NPs prepared by a water-oil-water emulsion and reduced pressure solvent evaporation technique were determined to have a positive zeta potential, a capsule-like morphology, and an average hydrodynamic diameter of 240 nm. Entrapment of NVP as a single ARV had a notable increase in NP size compared to LMV alone or in combination with LMV. NPs stored at room temperature in distilled water maintained size, polydispersity (PDI), and zeta potential for one year. No changes in size, PDI, and zeta potential were observed for NPs in 10% sucrose in lyophilized or nonlyophilized states stored at 4 degrees C and -20 degrees C, respectively. Freezing NPs in the absence of sucrose increased NP size. Drug loading, encapsulation efficiency, and kinetic release profiles were quantified by high performance liquid chromatography (HPLC). Our novel nanoformulations have the potential to improve patient outcomes and expand drug access in resource limited countries for the treatment of HIV-1. PMID- 27190653 TI - Early Functional Treatment and Modern Cast Making for Indications in Hand Surgery. AB - Cast treatment can serve both as a nonsurgical treatment option and as a means for providing postoperative protection. However, with the duration of immobilization intervals, the benefits of cast treatment, especially in hand surgery, are at risk of being outweighed by undesired drawbacks such as joint stiffening and contracture formation. In order to minimize potential complications commonly associated with cast treatment, efforts to further improve cast making must attempt to reconcile two conflicting objectives: (1) to achieve stability and rigidity at the site of injury (e.g., fracture retention) and (2) to allow free range of joint movement as early as possible. In addition, in order to assure patient compliance, modern cast treatments should aim to improve wearing-comfort of the cast. This paper describes modern cast designs for four common types hand injuries, with sample cases highlighting the clinical outcome of each treatment. PMID- 27190656 TI - Ventricular Septal Perforation after Biventricular Takotsubo Cardiomyopathy Successfully Repaired with an Amplatzer Device: First Report in the Literature. AB - A 79-year-old female was admitted with sudden onset dyspnea, mild oppressive chest pain, and severe anxiety disorder. Patient had history of hypertension, dyslipidemia, smoking, and chronic obstructive pulmonary disease. On admission blood pressure was 160/90 and heart rate was 130 bpm. Transthoracic echocardiography (TE) and contrast tomography showed a thin septum with an abnormal left and right ventricular contraction with an "apical ballooning" pattern and mild increase of cardiac enzymes. At the 4th day of admission, the patient presented symptoms and signs of congestive heart failure and developed cardiogenic shock. EKG showed an inversion of T waves in all precordial leads. In a new TE, a ventricular septal perforation (VSP) in the apical portion of the septum was seen. Coronary angiogram showed angiographically "normal" coronary arteries. With a diagnosis of VSP in takotsubo cardiomyopathy, a percutaneous procedure to repair the VSP was performed 11 days after admission. The VSP was closed with an Amplatzer device. TE performed 24 hours after showed significant improvement of ventricular function and good apposition of the Amplatzer device. Three days later she was discharged from the hospital. To our knowledge, this is the first reported case of a VSP in a TCM repaired percutaneously with an occluder device. PMID- 27190655 TI - Role of Striatal-Enriched Tyrosine Phosphatase in Neuronal Function. AB - Striatal-enriched protein tyrosine phosphatase (STEP) is a CNS-enriched protein implicated in multiple neurologic and neuropsychiatric disorders. STEP regulates key signaling proteins required for synaptic strengthening as well as NMDA and AMPA receptor trafficking. Both high and low levels of STEP disrupt synaptic function and contribute to learning and behavioral deficits. High levels of STEP are present in human postmortem samples and animal models of Alzheimer's disease, Parkinson's disease, and schizophrenia and in animal models of fragile X syndrome. Low levels of STEP activity are present in additional disorders that include ischemia, Huntington's chorea, alcohol abuse, and stress disorders. Thus the current model of STEP is that optimal levels are required for optimal synaptic function. Here we focus on the role of STEP in Alzheimer's disease and the mechanisms by which STEP activity is increased in this illness. Both genetic lowering of STEP levels and pharmacological inhibition of STEP activity in mouse models of Alzheimer's disease reverse the biochemical and cognitive abnormalities that are present. These findings suggest that STEP is an important point for modulation of proteins required for synaptic plasticity. PMID- 27190657 TI - Pancreaticopericardial Fistula: A Case Report and Literature Review. AB - Purpose. Pancreaticopericardial fistula (PPF) is an extremely rare complication of acute or chronic pancreatitis. This paper presents a rare case of PPF and provides systematic review of existing cases from 1970 to 2014. Methods. A PubMed search using key words was performed for all the cases of PPF from January 1970 to December 2014. Fourteen cases were included in the study. The cases were reviewed for demographic characteristics, diagnostic modalities, and treatment. Descriptive analysis of these variables was performed. Results. Median age was 43 years. 78% were known alcoholics and 73.3% had chronic pancreatitis. Dyspnea was present in 78%. Cardiac tamponade was present in 53%; 75% of patients had known chronic pancreatitis (RR = 0.74). Surgery was associated with best treatment outcomes and 50% of patients who underwent endoscopic treatment survived. Conclusion. PPF is a rare disease. This paper indicates that acute cardiac tamponade in patients with history of alcoholism and chronic pancreatitis could be a sign of an existing pancreaticopericardial fistula and early surgical intervention could be life-saving. PMID- 27190658 TI - Implant-Prosthetic Rehabilitation in Bilateral Agenesis of Maxillary Lateral Incisors with a Mini Split Crest. AB - The reported clinical case describes the surgical procedure of ridge augmentation by using a "split crest" technique with a partial thickness flap and a subsequent implant-prosthetic rehabilitation aimed at treating a bilateral agenesis of the upper lateral incisors. In such cases with vestibule-palatal and mesial-distal scarce bone thicknesses associated with the need of a proper functional and aesthetic rehabilitation, the split crest technique is particularly suitable. In the case we reported, because of the poor bone thicknesses, we performed a minimally invasive split crest which allowed a correct insertion of the fixtures. This technique allowed us to achieve an optimal functional and aesthetic rehabilitation; moreover, we obtained a good emergency profile, ensuring the vitality of the close teeth and ensuring a good primary stability and the following osseointegration of dental implants. PMID- 27190654 TI - Form and Function of Sleep Spindles across the Lifespan. AB - Since the advent of EEG recordings, sleep spindles have been identified as hallmarks of non-REM sleep. Despite a broad general understanding of mechanisms of spindle generation gleaned from animal studies, the mechanisms underlying certain features of spindles in the human brain, such as "global" versus "local" spindles, are largely unknown. Neither the topography nor the morphology of sleep spindles remains constant throughout the lifespan. It is likely that changes in spindle phenomenology during development and aging are the result of dramatic changes in brain structure and function. Across various developmental windows, spindle activity is correlated with general cognitive aptitude, learning, and memory; however, these correlations vary in strength, and even direction, depending on age and metrics used. Understanding these differences across the lifespan should further clarify how these oscillations are generated and their function under a variety of circumstances. We discuss these issues, and their translational implications for human cognitive function. Because sleep spindles are similarly affected in disorders of neurodevelopment (such as schizophrenia) and during aging (such as neurodegenerative conditions), both types of disorders may benefit from therapies based on a better understanding of spindle function. PMID- 27190659 TI - Paraneoplastic Pemphigus Associated with Follicular Dendritic Cell Tumor in the Mediastinum. AB - Paraneoplastic Pemphigus (PNP) is an autoimmune bullous disease characterized by severe stomatitis, polymorphous skin eruptions, and underlying neoplasms. Diagnosis of cutaneous paraneoplastic disorders requires high index of suspicion. We describe a patient with PNP associated with follicular dendritic cell (FDC) tumor in the mediastinum, a rare neoplasm originating from follicular dendritic cells. Its management requires identification of underlying malignancy and treatment of the same. Our patient showed remission of PNP upon excision of the tumor and remained disease-free for 8 years. PMID- 27190660 TI - CMV Colitis in Immunocompetent Patients: 2 Cases of a Diagnostic Challenge. AB - CMV infections are generally thought to be opportunistic by immunosuppression. Many literature cases though indicate that CMV infections can be also observed in immunocompetent patients. We present an unusual case of an extensive concentric benign stenosis due to CMV colitis and a case of coexistence with Crohn's Disease, both observed in nonimmunosuppressed individuals. The right diagnosis was set after implementation of multiple unsuccessful treatment strategies. Our purpose is therefore to familiarize clinicians involved with the diagnosis and treatment of gastroenterological diseases with this entity. PMID- 27190661 TI - Urticarial Vasculitis-Associated Intestinal Ischemia. AB - Urticarial vasculitis (UV) is a rare small vessel vasculitis. UV is often idiopathic but can also present in the context of autoimmune disorders such as systemic lupus erythematosus, drug reactions, infections, or a paraneoplastic syndrome. Extracutaneous complications include intestinal ischemic injuries, in UV patients with nonspecific gastrointestinal symptoms such as abdominal pain and nausea. Prompt recognition and treatment can minimize morbidity and mortality. This paper describes a case of urticarial vasculitis-associated intestinal ischemia. PMID- 27190662 TI - Suppression of Parathyroid Hormone in a Patient with Severe Magnesium Depletion. AB - Hypomagnesemia is often associated with coexisting electrolyte abnormalities like hypokalemia and hypocalcemia. Hypocalcemia has been shown to be secondary to hypoparathyroidism induced by hypomagnesemia. Here, we discuss a case of a patient with severe hypomagnesemia and associated hypocalcemia. A 38-year-old lady was admitted to the hospital for weakness of lower extremities and an eventual fall. The exam was significant for decreased motor strength and some paresthesias. The laboratory data was significant for hypomagnesemia, hypokalemia, and low parathyroid level in the face of hypocalcemia. After replacing magnesium, the parathyroid hormone levels normalized and led to eventual correction of calcium levels without any additional calcium replacement therapy. There was complete symptom resolution with correction of electrolyte abnormalities. This case highlights the importance of looking for all associated abnormalities in a patient with hypomagnesemia and starting the replacement therapy by first replacing the magnesium and then the others as needed. Replacing the magnesium alone may correct the hypoparathyroidism and eliminate the need for calcium replacement. PMID- 27190663 TI - Profound Autonomic Instability Complicated by Multiple Episodes of Cardiac Asystole and Refractory Bradycardia in a Patient with Anti-NMDA Encephalitis. AB - Anti-N-methyl-d-aspartate receptor encephalitis (anti-NMDARE) is autoimmune encephalitis primarily affecting young adults and children. First described about a decade ago, it frequently manifests as a syndrome that includes progressive behavioral changes, psychosis, central hypoventilation, seizures, and autonomic instability. Although cardiac arrhythmias often accompany anti-NMDARE, the need for long-term electrophysiological support is rare. We describe the case of NMDARE whose ICU course was complicated by progressively worsening episodes of tachyarrhythmia-bradyarrhythmia and episodes of asystole from which she was successfully resuscitated. Her life-threatening episodes of autonomic instability were successfully controlled only after the placement of a permanent pacemaker during her ICU stay. She made a clinical recovery and was discharged to a skilled nursing facility after a protracted hospital course. PMID- 27190664 TI - Case Report of a Traumatic Atlantoaxial Rotatory Subluxation with Bilateral Locked Cervical Facets: Management, Treatment, and Outcome. AB - The aim was to report a rare case of isolated traumatic atlantoaxial rotatory subluxation without ligamentous injury. Management consisted of analgesia, sedation, and application of a halo skull traction device. After removing halo skull traction, full reduction and recovery were achieved without instability. PMID- 27190665 TI - Congenital Temporomandibular Joint Ankylosis: Case Report and Literature Review. AB - Congenital temporomandibular joint (TMJ) ankylosis is an uncommon condition that presents itself at or soon after birth in the absence of acquired factors that could have contributed to the ankylosis such as infection and trauma. The experience of managing one such case is reported in light of a review of the literature on this condition. Key management principles include adequate removal of the ankylotic mass, costochondral grafting, and post-op physiotherapy. Most patients reported in the literature with the condition experienced relapse. This echoes our own experience where there was recurrence of the ankylosis. However, after removal of the ankylotic mass, the patient maintains a satisfactory maximal incisal opening (MIO) till the present day. The additional challenges faced in the congenital form in addition to the already complex management of acquired paediatric temporomandibular joint ankylosis are (1) much earlier insult to the TMJ, (2) reduced opportunity for neuromuscular development of the muscles of mastication, and (3) reduced compliance with postoperative physiotherapy programmes due to the younger age of these patients. PMID- 27190666 TI - Clostridium difficile Enterocolitis and Reactive Arthritis: A Case Report and Review of the Literature. AB - Reactive arthritis is a rare complication of Clostridium difficile enterocolitis, especially in children. We review the 6 pediatric cases published in the English and non-English literature and discuss their clinical presentation, outcome, treatment, and pathophysiology. We also report the seventh case of Clostridium difficile reactive arthritis in a 6-year-old boy who was treated with amoxicillin clavulanate for 10 days because of an upper respiratory infection. After the antibiotic course, the child developed at the same time diarrhea with positive stool culture for Clostridium difficile and an asymmetric polyarthritis. Nonsteroidal anti-inflammatory drugs and metronidazole completely resolved the pain, joint swelling, and diarrhea. After twelve months of follow-up there has been no recurrence. This report confirms the self-limiting course of Clostridium difficile reactive arthritis. Clostridium difficile testing in children with gastrointestinal symptoms and acute onset of joint pain should be always considered. PMID- 27190667 TI - Severe Acute Pulmonary Toxicity Associated with Brentuximab in a Patient with Refractory Hodgkin's Lymphoma. AB - Acute pulmonary toxicity associated with brentuximab appears to be a rare but serious adverse effect that can be potentially fatal. We report the case of a twenty-nine-year-old female with Hodgkin's lymphoma who was treated with brentuximab and later presented with severe acute pulmonary toxicity; she improved after the discontinuation of brentuximab and administration of antibiotics and glucocorticoid therapy. Currently there is very little data in the literature in regard to the clinical manifestations and characteristics of patients taking brentuximab and the potential development of acute severe pulmonary toxicity, as well as the appropriate therapeutic approach, making this particular case of successful treatment and resolution unique. PMID- 27190668 TI - Acute Abdominal Pain Caused by an Infected Mesenteric Cyst in a 24-Year-Old Female. AB - A mesenteric cyst is a rare cause for abdominal pain. This umbrella term includes cystic entities which reside in the mesentery. We present a case of an infected false mesenteric cyst in a 24-year-old female patient without prior surgery or known trauma. Mainstay of treatment involves surgical resection, although less invasive treatments have been described. Prognosis depends on the origin of the cyst. PMID- 27190669 TI - Primary Hydatid Cyst of Umbilicus, Mimicking an Umbilical Hernia. AB - Hydatid cyst caused by Echinococcus granulosus demonstrates an endemic infection in several countries such as Middle Eastern countries. Liver is the most frequently involved organ, followed by the lung. The case we present is solitary primary localization of cyst in abdominal wall which is extremely rare. A 57-year old woman presented with an abdominal wall lesion in umbilical area that had been evolving for about 2 years with recent complaint of pain and discomfort. We detected a midline abdominal mass 12*13 centimeters in diameter which was bulged out in umbilicus. Preoperative clinical diagnosis of incarcerated umbilical hernia was made due to its physical examination while surgical exploration disproved the primary diagnosis and we found cystic mass adherent to superficial fascia without any communication to peritoneal space. The cyst was excised completely without any injury or perforation of containing capsule. The diagnosis of hydatid cyst was confirmed by histopathological examination of specimen. The retrograde evaluation showed no involvement of other organs. The patient was followed for two years and no recurrence of hydatid disease has been observed. Hydatid cyst should be considered as a differential diagnosis of abdominal wall and umbilical lesions especially in endemic regions. PMID- 27190670 TI - Posttransurethral Resection of Prostate Recurrent Life Threatening Hematuria: A Rare Cause. AB - Herein, we present a case report of post-TURP (transurethral resection of prostate) recurrent severe hematuria due to right internal iliac artery pseudoaneurysm protruding into bladder lumen. A 60-year-old male presented with recurrent massive hematuria following TURP done elsewhere 15 days before. His hemoglobin was 4 gm/dL after 13 units of blood transfusion and repeated clot evacuations. His blood urea, serum creatinine, and coagulation profile studies were normal. Ultrasonography of abdomen showed multiple clots in the bladder. Cystoscopy revealed clots with a right posterolateral wall unhealthy area. After stabilizing the patient, contrast enhanced CT urography revealed intravesical aneurysm. CT angiography showed pseudoaneurysm of a branch of internal iliac artery protruding into urinary bladder lumen. We referred patient to selective embolization of the lesion but the procedure was unsuccessful. At last, ipsilateral internal iliac artery ligation relieved hematuria. But on postoperative day 2, patient suddenly collapsed and deceased, presumably due to cardiomorbidities. PMID- 27190671 TI - Increased Prevalence of Mutant Allele Pfdhps 437G and Pfdhfr Triple Mutation in Plasmodium falciparum Isolates from a Rural Area of Gabon, Three Years after the Change of Malaria Treatment Policy. AB - In Gabon, sulfadoxine-pyrimethamine (SP) is recommended for intermittent preventive treatment during pregnancy (IPTp-SP) and for uncomplicated malaria treatment through ACTs drug. P. falciparum strains resistant to SP are frequent in areas where this drug is highly used and is associated with the occurrence of mutations on Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and dihydropteroate synthetase (Pfdhps) genes. The aim of the study was to compare the proportion of mutations on Pfdhfr and Pfdhps genes in isolates collected at Oyem in northern Gabon, in 2005 at the time of IPTp-SP introduction and three years later. Point mutations were analyzed by nested PCR-RFLP method. Among 91 isolates, more than 90% carried Pfdhfr 108N and Pfdhfr 59R alleles. Frequencies of Pfdhfr 51I (98%) and Pfdhps 437G (67.7%) mutant alleles were higher in 2008. Mutations at codons 164, 540, and 581 were not detected. The proportion of the triple Pfdhfr mutation and quadruple mutation including A437G was high: 91.9% in 2008 and 64.8% in 2008, respectively. The present study highlights an elevated frequency of Pfdhfr and Pfdhps mutant alleles, although quintuple mutations were not found in north Gabon. These data suggest the need of a continuous monitoring of SP resistance in Gabon. PMID- 27190672 TI - Structural Neuroimaging Markers of Cognitive Decline in Parkinson's Disease. AB - Cognitive impairment in patients with Parkinson's disease is a major challenge since it has been established that 25 to 40% of patients will develop cognitive impairment early in the disease. Furthermore, it has been reported that up to 80% of Parkinsonian patients will eventually develop dementia. Thus, it is important to improve the diagnosing procedures in order to detect cognitive impairment at early stages of development and to delay as much as possible the developing of dementia. One major challenge is that patients with mild cognitive impairment exhibit measurable cognitive deficits according to recently established criteria, yet those deficits are not severe enough to interfere with daily living, hence being avoided by patients, and might be overseen by clinicians. Recent advances in neuroimaging brain analysis allowed the establishment of several anatomical markers that have the potential to be considered for early detection of cognitive impairment in Parkinsonian patients. This review aims to outline the neuroimaging possibilities in diagnosing cognitive impairment in patients with Parkinson's disease and to take into consideration the near-future possibilities of their implementation into clinical practice. PMID- 27190673 TI - Whole-Brain Atrophy Rate in Idiopathic Parkinson's Disease, Multiple System Atrophy, and Progressive Supranuclear Palsy. AB - In multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), the absence of surrogate endpoints makes clinical trials long and expensive. We aim to determine annualized whole-brain atrophy rates (a-WBAR) in idiopathic Parkinson's disease (IPD), MSA, and PSP. Ten healthy controls, 20 IPD, 12 PSP, and 8 MSA patients were studied using a volumetric MRI technique (SIENA). In controls, the a-WBAR was 0.37% +/- 0.28 (CI 95% 0.17-0.57), while in IPD a-WBAR was 0.54% +/- 0.38 (CI 95% 0.32-0.68). The IPD patients did not differ from the controls. In PSP, the a-WBAR was 1.26% +/- 0.51 (CI 95%: 0.95-1.58). In MSA, a WBAR was 1.65% +/- 1.12 (CI 95%: 0.71-2.59). MSA did not differ from PSP. The a WBAR in PSP and MSA were significantly higher than in the IPD group (p = 0.004 and p < 0.001, resp.). In PSP, the use of a-WBAR required one-half of the patients needed for clinical scales to detect a 50% reduction in their progression. In MSA, one-quarter of the patients would be needed to detect the same effect. a-WBAR is a reasonable candidate to consider as a surrogate endpoint in short clinical trials using smaller sample sizes. The confidence intervals for a-WBAR may add a potential retrospective application for a-WBAR to improve the diagnostic accuracy of MSA and PSP versus IPD. PMID- 27190675 TI - The Laplacian-Energy-Like Invariants of Three Types of Lattices. AB - This paper mainly studies the Laplacian-energy-like invariants of the modified hexagonal lattice, modified Union Jack lattice, and honeycomb lattice. By utilizing the tensor product of matrices and the diagonalization of block circulant matrices, we derive closed-form formulas expressing the Laplacian energy-like invariants of these lattices. In addition, we obtain explicit asymptotic values of these invariants with software-aided computations of some integrals. PMID- 27190674 TI - Effect of Treatment Delay, Stroke Type, and Thrombolysis on the Effect of Glyceryl Trinitrate, a Nitric Oxide Donor, on Outcome after Acute Stroke: A Systematic Review and Meta-Analysis of Individual Patient from Randomised Trials. AB - Background. Nitric oxide (NO) donors are a candidate treatment for acute stroke and two trials have suggested that they might improve outcome if administered within 4-6 hours of stroke onset. We assessed the safety and efficacy of NO donors using individual patient data (IPD) from completed trials. Methods. Randomised controlled trials of NO donors in patients with acute or subacute stroke were identified and IPD sought from the trialists. The effect of NO donor versus control on functional outcome was assessed using the modified Rankin scale (mRS) and death, by time to randomisation. Secondary outcomes included measures of disability, mood, and quality of life. Results. Five trials (4,197 participants) were identified, all involving glyceryl trinitrate (GTN). Compared with control, GTN lowered blood pressure by 7.4/3.3 mmHg. At day 90, GTN did not alter any clinical measures. However, in 312 patients randomised within 6 hours of stroke onset, GTN was associated with beneficial shifts in the mRS (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.34-0.78) and reduced death (OR 0.32, 95% CI 0.14-0.78). Conclusions. NO donors do not alter outcome in patients with recent stroke. However, when administered within 6 hours, NO donors might improve outcomes in both ischaemic and haemorrhagic stroke. PMID- 27190676 TI - Synthesis and Antibacterial Activity of 3-(Substituted)-2-(4-oxo-2 phenylquinazolin-3(4H)-ylamino)quinazolin-4(3H)-one. AB - A series of novel 3-(substituted)-2-(substituted quinazolinylamino)quinazolin 4(3H)-ones were synthesized by the reaction of 3-(substituted)-2-hydrazino quinazoline-4(3H)-ones with 2-phenyl-3,1-benzoxazin-4-one. The starting materials 3-(substituted)-2-hydrazino-quinazolin-4(3H)-ones were synthesized from various primary amines by a multistep synthesis. All the title compounds were tested for their antibacterial activity using ciprofloxacin as reference standard. Compounds 3-(4-fluorophenyl)-2-(4-oxo-2-phenylquinazolin-3(4H)-ylamino)quinazolin-4(3H)-one (9a) and 3-(4-chlorophenyl)-2-(4-oxo-2-phenylquinazolin-3(4H)-ylamino)quinazolin 4(3H)-one (9h) emerged as the most active compounds of the series. These compounds have shown most potent antibacterial activity against the tested organisms of Proteus vulgaris and Bacillus subtilis having zone of inhibition values of 1.1 cm and 1.4 cm for compound 9a 1.2 cm and 1.0 cm for compound 9h, respectively. PMID- 27190677 TI - Essential Oil Yield Pattern and Antibacterial and Insecticidal Activities of Trachyspermum ammi and Myristica fragrans. AB - Two Indian spices, Trachyspermum ammi and Myristica fragrans, were studied for their essential oil (EO) yielding pattern, insecticidal activity, antibacterial activity, and composition. The essential oils (EOs) of T. ammi (1.94 +/- 30 mL/100 gm) and M. fragrans (5.93 +/- 90 mL/100 gm) were extracted using hydrodistillation method. In Gas Chromatography analysis, the beta-pinene, alpha pinene, alpha-p-menth-1-en-4-ol, Limonene, and elemicin were found as major constituents of T. ammi essential oil whereas M. fragrans essential oil mostly contains Gamma-Terpinolene, p-Cymene, Thymol, and beta-pinene. The insecticidal activities of EO were demonstrated using LC50 values against Plodia interpunctella and EO of T. ammi was found comparatively more effective than EO of M. fragrans. Further, individual EO and combination of essential oil were examined for antibacterial activity against three Gram (-) bacterial strains (E. coli-MTCC 443, P. vulgaris-MTCC 1771, and K. pneumoniae-MTCC number 7028) and three Gram (+) bacterial strains (S. aureus-MTCC 3381, B. subtilis-MTCC 10619, and B. megaterium-MTCC 2412) by well agar diffusion method. The essential oil in combination (CEO) exhibited higher antibacterial activity as compared with individual essential oils. PMID- 27190679 TI - Safety Evaluation of Unani Formulation: Capsule Shaqeeqa in Albino Wistar Rats. AB - Capsule Shaqeeqa, Unani formulation, is prescribed for the clinical treatment of diseases like sinusitis, headache, and migraine. The safety evaluation data of it is not available; in order to provide the safety data the present study was carried out. The study was carried out on four groups of rats (n = 5). Two groups (one male and one female group) as normal controls were orally given water while the other two groups were orally given daily doses of drug at the dose level of 150 mg/kg of body weight for duration of 90 days. Physiological parameters like body weight, feed consumption, water consumption, and clinical signs were regularly monitored and recorded. Organs were collected, examined, and weighed and specimens were taken for histopathological studies. The results showed that the drug did not alter the physiological parameters. There was no mortality or any morbidity found in drug treated rats. There was no statistical significant change found in any haematological or biochemical parameter of rats orally fed with Shaqeeqa. A statistically insignificant association verified that haematological and biochemical parameters were rendered unaffected by the drug. Moreover histological investigations of essential key organs demonstrated that the drug did not prompt any histopathological change. These observations demonstrate the safety of Capsule Shaqeeqa at the studied dosage levels. PMID- 27190680 TI - Skeletal and Dentoalveolar Cephalometric Features of Anterior Open Bite among Yemeni Adults. AB - Objective. The aim of this study is to determine the cephalometric features for a sample of Yemeni adults with anterior open bite. Material and Methods. Lateral cephalometric radiographs were taken for 65 Yemeni university students (46 males and 19 females), 18-25 years old, with clinical anterior open bite (vertical overbite <= 0 mm) and no previous orthodontic treatment. The radiographs were manually traced; twelve angular, five linear measurements, and facial index were assessed, analyzed statistically, and compared to 194 Yemeni norms (89 males and 105 females) as well as cephalometric features of open bite subjects in previous studies. Results. Statistically significant differences were observed in skeletal and dental cephalometric values of Yemeni patients with anterior open bite when compared to Yemeni norms; mainly in the anteroposterior relation, the open bite individuals had higher significant value in SNA, SNB, and SNPg angles. In addition, a higher statistical significant difference was recorded in all variables of vertical relation when compared with norms. In contrast, NL-NSL angle revealed higher value among normal individuals. Dental variables among open bite individuals showed a greater degree of dental proclination, higher statistically significant value in [Formula: see text]-NA degrees , [Formula: see text]-NA mm and I-NB mm, and a lower significant value in U1-L1 in open bite group. Conclusion. Open bite Yemeni individual's skeletal and dentoalveolar variables significantly differ from Yemeni norms in the extent of the anteroposterior, vertical developmental pattern and dental relations. PMID- 27190678 TI - The Use of Heparin during Endovascular Peripheral Arterial Interventions: A Synopsis. AB - A large variety exists for many aspects of the use of heparin as periprocedural prophylactic antithrombotics (PPAT) during peripheral arterial interventions (PAI). This variation is present, not only within countries, but also between them. Due to a lack of (robust) data, no systematic review on the use of heparin during PAI could be justified. A synopsis of all available literature on heparin during PAI describes that heparin is used on technical equipment to reduce the thrombogenicity and in the flushing solution with saline. Heparin could have a cumulative anticoagulant effect when used in combination with ionic contrast medium. No level-1 evidence exists on the use of heparin. A measurement of actual anticoagulation status by means of an activated clotting time should be mandatory. PMID- 27190681 TI - Trends in the Diagnosis of Gestational Diabetes Mellitus. AB - Introduction. Gestational diabetes mellitus (GDM) is defined as carbohydrate intolerance of variable degree with onset or recognition during pregnancy. As prevalence of diabetes is linked to impaired glucose tolerance during antenatal period, routine antenatal screening of GDM is required. However, screening tests for GDM remain controversial. Objective. To review different diagnostic criteria for GDM. Materials and Methods. Freely accessible, full-text articles from 1964 to 2015, available in PubMed in English language, pertaining to screening of GDM were reviewed. Results. First diagnostic criteria for GDM in 1964 by O'Sullivan and Mahan, modified by the National Diabetes Data Group (NDDG) in 1979 and Carpenter in 1982. The cut-off value as per WHO definition of GDM was 140 mg/dL, 2 hours after 75 g glucose intake. Diabetes in Pregnancy Study Group India (DIPSI), in 2006, endorsed WHO criteria but irrespective of the last meal timings. Being cost-effective, it formed the basis of national guidelines for Indians in 2014. Conclusions. As typical clinical scenarios are usually varied, practical guidelines that meet the constraints of low-resource settings like India are required. PMID- 27190682 TI - Ultrasound Assessment of Synovial Thickness of Some of the Metacarpophalangeal Joints of Hand in Rheumatoid Arthritis Patients and the Normal Population. AB - Objective. To compare ultrasound synovial thickness of the 2nd, 3rd and 4th metacarpophalangeal joints (MCPJ) in a group of patients with proven rheumatoid arthritis (RA) and a control group of normal individuals. Materials and Methods. This is a cross-sectional study comprising 30 rheumatoid arthritis patients and 30 healthy individuals. Ultrasound scans were performed at the dorsal side of 2nd, 3rd, and 4th MCPJ of both hands in RA patients and the healthy individuals. Synovial thickness was measured according to quantitative method. The synovial thickness of RA patients and healthy individuals was compared and statistical cut off was identified. Results. Maximum synovial thickness was most often detected at the radial side of the 2nd MCPJ and 3rd MCPJ and ulnar side of the 4th MCPJ of both hands which is significantly higher (p < 0.05) in RA patients compared to healthy individuals. With high specificity (96%) and sensitivity (90%) the optimum cut-off value to distinguish RA patients and healthy individuals' synovial thickness differs for the radial side of the 2nd and 3rd MCPJ and ulnar side of the 4th MCPJ. Conclusion. Patients with early RA appear to exhibit a characteristic pattern of synovitis which shows radial side predominance in the 2nd and 3rd MCPJ and ulnar side in the 4th MCPJ. PMID- 27190683 TI - Symptoms of Poststroke Depression among Stroke Survivors: An Appraisal of Psychiatry Needs and Care during Physiotherapy Rehabilitation. AB - Purpose. To identify stroke survivors with symptoms of poststroke depression and the extent of psychiatry needs and care they have received while on physiotherapy rehabilitation. Participants. Fifty stroke survivors (22 females and 28 males) at the outpatient unit of Physiotherapy Department, University of Nigeria Teaching Hospital, Enugu, who gave their informed consent, were randomly selected. Their age range and mean age were 26-66 years and 54.76 +/- 8.79 years, respectively. Method. A multiple case study of 50 stroke survivors for symptoms of poststroke depression was done with Beck's Depression Inventory, mini mental status examination tool, and Modified Motor Assessment Scale. The tests were performed independently by the participants except otherwise stated and scored on a scale of 0-6. Data were analyzed using Z-test for proportional significance and chi square test for determining relationship between variables, at p < 0.05. Results. Twenty-one (42.0%) stroke survivors had symptoms of PSD, which was significantly dependent on duration of stroke (chi (2) = 21.680, df = 6, and p = 0.001), yet none of the participants had a psychiatry review. Conclusions. Symptoms of PSD may be common in cold compared to new cases of stroke and may need psychiatry care while on physiotherapy rehabilitation. PMID- 27190685 TI - A Mixed Method Research to Identify Perceived Reasons and Solutions for Low Uptake of Cervical Cancer Screening in Urban Families of Bhopal Region. AB - Low uptake of cervical cancer screening is not a matter of poor coverage of health care facilities only. We wish to identify the perceived reasons behind low uptake of screening in Bhopal region and also possible solutions for an urban setting. In a mixed research, through a series of focused group discussions, we wished to do thematic interpretation of the perceptions towards cervical cancer screening by deductive content analysis of FGD and also to obtain a free list of perceived causes and solutions with Smith's saliency score and perform cluster analysis by pile sorting. We found that the perceived reasons could be grouped into three themes which were (1) information gap leading to fear of unknown, (2) casual attitude, and (3) resource constrains and affordability issues. For the perceived solutions there were 11 codes which could be grouped into two groups; these were increasing awareness and vaccination. Free list of perceived reasons and solutions has also been generated. No single solution can be suggested but a comprehensive approach with awareness campaigns, personalized encouragements, affordable and friendly health care with subsidized vaccination, and screening facilities are expected to increase awareness and acceptability and thus reduce burden of disease in the long run. PMID- 27190684 TI - Updated Methods for Seed Shape Analysis. AB - Morphological variation in seed characters includes differences in seed size and shape. Seed shape is an important trait in plant identification and classification. In addition it has agronomic importance because it reflects genetic, physiological, and ecological components and affects yield, quality, and market price. The use of digital technologies, together with development of quantification and modeling methods, allows a better description of seed shape. Image processing systems are used in the automatic determination of seed size and shape, becoming a basic tool in the study of diversity. Seed shape is determined by a variety of indexes (circularity, roundness, and J index). The comparison of the seed images to a geometrical figure (circle, cardioid, ellipse, ellipsoid, etc.) provides a precise quantification of shape. The methods of shape quantification based on these models are useful for an accurate description allowing to compare between genotypes or along developmental phases as well as to establish the level of variation in different sets of seeds. PMID- 27190686 TI - Broad Spectrum Anti-Quorum Sensing Activity of Tannin-Rich Crude Extracts of Indian Medicinal Plants. AB - Quorum sensing (QS) mechanisms have been demonstrated to have significance in expression of pathogenicity in infectious bacteria. In Gram negative bacteria the autoinducer molecules that mediate QS are acyl homoserine lactones (AHL) and in Gram positive bacteria they are peptides called autoinducing peptides (AIP). A screening of tannin-rich medicinal plants was attempted to identify extracts that could interrupt the QS mechanisms in both Gram positive and Gram negative bacteria over a wide range of concentrations and therefore potentially be potent agents that could act as broad spectrum QS inhibitors. Six out of the twelve Indian medicinal plant extracts that were analyzed exhibited anti-QS activity in Chromobacterium violaceum 12472 and in S. aureus strain with agr:blaZ fusion over a broad range of subinhibitory concentrations, indicating that the extracts contain high concentration of molecules that can interfere with the QS mechanisms mediated by AHL as well as AIP. PMID- 27190688 TI - Efficacy of a Novel Topical Combination of Fipronil 9.8% and (S)-Methoprene 8.8% against Ticks and Fleas in Naturally Infested Dogs. AB - The efficacy of a novel topical combination of fipronil 9.8% (w/v) and (S) methoprene 8.8% (w/v) (Fiprofort(r) Plus) was tested against ticks and fleas in naturally infested dogs. A total of fifty dogs were allocated in the study with ticks infestation (n = 35) and fleas infestation (n = 15). On day 0, thirty-five tick and fifteen flea infested dogs received the test formulation, a combination of fipronil 9.8% (w/v) and (S)-methoprene 8.8% (w/v) spot-on solution. Ticks and flea counts were taken on days 0 (pretreatment) and 3, 7, 14, 21, 28, and 35 after treatment. Blood samples were collected for evaluation of haematological parameters on days 0 (pretreatment) and 7, 21, and 35 after treatment. All the adult ticks and fleas collected were identified as Rhipicephalus sanguineus and Ctenocephalides felis, respectively. The efficacy of spot-on formulation against ticks was 34.00% (day 3), 53.14% (day 7), 62.71% (day 14), 65.48% (day 21), 59.80% (day 28), and 58.82% (day 35), whereas against fleas it was 38.00% (day 3), 64.34% (day 7), 89.67% (day 14), 95.40% (day 21), 100.00% (day 28), and 100.00% (day 35). Haematological parameters for ticks and fleas infested dogs were statistically nonsignificant as compared to control. The combination of fipronil and (S)-methoprene eliminated the existing ticks and fleas infestation and prevented the dogs from flea and tick infestation for four weeks. PMID- 27190689 TI - Vasorelaxation Effect of Estrone Derivate EA204 in Rabbit Aorta. AB - Estrogen and its derivatives exert vascular protective effects, but the underlying mechanisms remain to be studied fully. Objective. To investigate the vasorelaxation effect and related mechanisms of an estrone derivate EA204[3-(2 piperidin-1-yl)-ethoxy-estra-1, 3, 5 (10)-trien-17-one] on isolated arterial preparation from rabbit thoracic aorta. Methods. Aortic rings from rabbit thoracic aorta were prepared and held in small organ bath filled with Krebs solution; tension change was recorded by a multichannel physiological signal collection and handling system. Results. EA204 (10(-5) to 10(-3) M) induced a concentration-dependent relaxation of aortic rings with endothelium and without endothelium. In denuded arterial preparations, EA204 had a potent relaxing effect on isolated arterial preparations contracted with phenylephrine, norepinephrine, and high-K(+) solution or BaCl2. Mechanism study indicates that EA204 relaxes aortic rings by inhibiting Ca(2+) channels (both receptor-operating Ca(2+) channels and the voltage-dependent Ca(2+) channels were involved) to decrease extracellular Ca(2+) influx and intracellular Ca(2+) release. EA204 is different from verapamil, which is a noncompetitive inhibitor of Ca(2+) channels. In addition, K(+) channels opening may contribute to this vasorelaxation effect. Conclusion. EA204 had a potent endothelium-independent relaxing effect on isolated arterial preparation by inhibiting Ca(2+) channels and opening K(+) channels. The results suggest that EA204 is a potential compound for treatment of cardiovascular diseases in postmenopausal women. PMID- 27190687 TI - Virulent Properties of Russian Bovine Viral Diarrhea Virus Strains in Experimentally Infected Calves. AB - The results of experimental study of three noncytopathic and two cytopathic bovine viral diarrhea virus (BVDV) strains isolated from cattle in the Siberian region and belonging to the type 1 (subtypes 1a, 1b, and 1d) have been presented. All investigated strains caused the development of infectious process in the seronegative 4-6-month-old calves after aerosol challenge with the dose of 6 log10 TCID50. The greatest virulence had noncytopathic strain and cytopathic strain related to the subtypes 1d and 1b, respectively. All strains in infected calves caused some signs of moderate acute respiratory disease and diarrhea: depression 3-5 days postinfection (p.i.), refusal to food, severe hyperthermia to 41.9 degrees S, serous exudate discharges from the nasal cavity and eyes, transient diarrhea with blood, leukopenia (up to 2700 cells/mm(3)), and macroscopic changes in the respiratory organs and intestine. The infected animals recovered from 12 to 15 days p.i. and in 90% cases formed humoral immune response 25 days p.i. (antibody titers to BVDV: 1 : 4-1 : 16). Our results confirmed the presence of virulent BVDV1 strains and showed the need for researches on the molecular epidemiology of the disease, development of more effective diagnostic systems, and optimization of control programs with use of vaccines. PMID- 27190690 TI - Emergency Peripartum Hysterectomies at a District General Hospital in United Kingdom: 10-Year Review of Practice. AB - Peripartum haemorrhage is an obstetric emergency which requires effective and timely management. A retrospective analysis was conducted at a single centre district hospital, over a 10-year period to describe factors that would lead to a peripartum hysterectomy. We sought to establish intraoperative and postoperative risks and review outcomes and complications associated with the procedure. A total of 29 cases (incidence 0.8 per 1000) were reviewed over 2001-2011. The mean parity was 1.8 and the mean maternal age was 33 years. Uterine atony was the most common indication for hysterectomy (12/29) followed by placenta praevia and accreta (4/29 and 5/29 cases, resp.). The commonest postoperative complications were sepsis and paralytic ileus. EPH most commonly occurs due to uterine atony but remains difficult to predict. Hospitals should continue to have robust systems and the necessary resources available to perform EPH where clinically indicated. PMID- 27190691 TI - Adverse Effects of Subchronic Dose of Aspirin on Reproductive Profile of Male Rats. AB - Aspirin (acetylsalicylic acid) is widely used for cardiovascular prophylaxis and as anti-inflammatory pharmaceutical. An investigation was carried out to evaluate the influence of subchronic dose of aspirin on reproductive profile of male rats, if any. Experimental animals were divided into three groups: control and aspirin subchronic dose of 12.5 mg/kg for 30 days and 60 days, respectively, while alterations in sperm dynamics, testicular histopathological and planimetric investigations, body and organs weights, lipid profiles, and hematology were performed as per aimed objectives. Subchronic dose of aspirin reduced sperm density, count, and mobility in cauda epididymis and testis; histopathology and developing primary spermatogonial cells (primary spermatogonia, secondary spermatogonia, and mature spermatocyte) count were also significantly decreased in rats. Hematological investigations revealed hemopoietic abnormalities in 60 day-treated animals along with dysfunctions in hepatic and renal functions. The findings of the present study revealed that administration with subchronic dose of aspirin to male rats resulted in altered reproductive profiles and serum biochemistry. PMID- 27190693 TI - Insulin resistance in development and progression of nonalcoholic fatty liver disease. AB - Although insulin resistance (IR) is strongly associated with nonalcoholic fatty liver disease (NAFLD), the association of IR and NAFLD is not universal and correlation between IR and severity of NAFLD is still controversial. In this review, we summarize recent evidence that partially dissociates insulin resistance from NAFLD. It has also been reported that single-nucleotide polymorphisms in the diacylglycerol acyltransferase gene, rather than IR, account for the variability in liver fat content. Polymorphisms of the patatin-like phospholipase 3 gene have also been reported to be associated with NAFLD without metabolic syndrome, which suggests that genetic conditions that promote the development of fatty changes in the liver may occur independently of IR. Moreover, environmental factors such as nutrition and physical activity as well as small intestinal bacterial overgrowth have been linked to the pathogenesis of NAFLD, although some of the data are conflicting. Therefore, findings from both genetically engineered animal models and humans with genetic conditions, as well as recent studies that have explored the role of environmental factors, have confirmed the view that NAFLD is a polygenic disease process caused by both genetic and environmental factors. Therefore, IR is not the sole predictor of the pathogenesis of NAFLD. PMID- 27190692 TI - Differential role of Hedgehog signaling in human pancreatic (patho-) physiology: An up to date review. AB - Since the discovery of the Hedgehog (Hh) pathway in drosophila melanogaster, our knowledge of the role of Hh in embryonic development, inflammation, and cancerogenesis in humans has dramatically increased over the last decades. This is the case especially concerning the pancreas, however, real therapeutic breakthroughs are missing until now. In general, Hh signaling is essential for pancreatic organogenesis, development, and tissue maturation. In the case of acute pancreatitis, Hh has a protective role, whereas in chronic pancreatitis, Hh interacts with pancreatic stellate cells, leading to destructive parenchym fibrosis and atrophy, as well as to irregular tissue remodeling with potency of initiating cancerogenesis. In vitro and in situ analysis of Hh in pancreatic cancer revealed that the Hh pathway participates in the development of pancreatic precursor lesions and ductal adenocarcinoma including critical interactions with the tumor microenvironment. The application of specific inhibitors of components of the Hh pathway is currently subject of ongoing clinical trials (phases 1 and 2). Furthermore, a combination of Hh pathway inhibitors and established chemotherapeutic drugs could also represent a promising therapeutic approach. In this review, we give a structured survey of the role of the Hh pathway in pancreatic development, pancreatitis, pancreatic carcinogenesis and pancreatic cancer as well as an overview of current clinical trials concerning Hh pathway inhibitors and pancreas cancer. PMID- 27190694 TI - Clinical impacts of mesothelin expression in gastrointestinal carcinomas. AB - Mesothelin, C-ERC/mesothelin is a 40-kDa cell surface glycoprotein that is normally present on normal mesothelial cells lining the pleura, peritoneum, and pericardium. Moreover, mesothelin has been shown to be overexpressed in several human cancers, including virtually all mesothelioma and pancreatic cancer, approximately 70% of ovarian cancer and extra bile duct cancer, and 50% of lung adenocarcinomas and gastric cancer. The full-length human mesothelin gene encodes the primary product, a 71-kDa precursor protein. The 71-kDa mesothelin precursor is cleaved into two products, 40-kDa C-terminal fragment that remains membrane bound via glycosylphosphatidylinositol anchor, and a 31-kDa N-terminal fragment, megakaryocyte potentiating factor, which is secreted into the blood. The biological functions of mesothelin remain largely unknown. However, results of recent studies have suggested that the mesothelin may play a role of cell proliferation and migration. In pancreatic cancer, mesothelin expression was immunohistochemically observed in all cases, but absent in normal pancreas and in chronic pancreatitis. Furthermore, the expression of mesothelin was correlated with an poorer patient outcome in several human cancers. The limited mesothelin expression in normal tissues and high expression in many cancers makes it an attractive candidate for cancer therapy. The present review discusses the expression and function of mesothelin in cancer cells and the utility of mesothelin as a target of cancer therapy. PMID- 27190695 TI - Sieving characteristics of cytokine- and peroxide-induced epithelial barrier leak: Inhibition by berberine. AB - AIM: To study whether the inflammatory bowel disease (IBD) colon which exhibits varying severity and cytokine levels across its mucosa create varying types of transepithelial leak. METHODS: We examined the effects of tumor necrosis factor alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-1-beta (IL1beta) and hydrogen peroxide (H2O2) - singly and in combinations - on barrier function of CACO-2 cell layers. Our focus was on the type (not simply the magnitude) of transepithelial leak generated by these agents as measured by transepithelial electrical resistance (TER) and transepithelial flux of (14)C-D-mannitol, (3)H Lactulose and (14)C-Polyethylene glycol as radiolabeled probe molecules. The isoquinoline alkaloid, berberine, was then examined for its ability to reduce specific types of transepithelial leak. RESULTS: Exposure to TNF-alpha alone (200 ng/mL; 48 h) induced a 50% decrease in TER, i.e., increased leak of Na(+) and Cl( ) - with only a marginal but statistically significant increase in transepithelial leak of (14)C-mannitol (Jm). Exposure to TNF-alpha + IFN-gamma (200 ng/mL; 48 h) + IL1beta (50 ng/mL; 48 h) did not increase the TER change (from TNF-alpha alone), but there was now a 100% increase in Jm. There however was no increase in transepithelial leak of two larger probe molecules, (3)H lactulose and (14)C-polyethylene glycol (PEG). However, exposure to TNF-alpha + IFN-gamma + IL1beta followed by a 5 h exposure to 2 mmol/L H2O2 resulted in a 500% increase in (14)C-PEG leak as well as leak to the luminal mitogen, epidermal growth factor. CONCLUSION: This model of graded transepithelial leak is useful in evaluating therapeutic agents reducing IBD morbidity by reducing barrier leak to various luminal substances. PMID- 27190696 TI - Visualization of sphingolipids and phospholipids in the fundic gland mucosa of human stomach using imaging mass spectrometry. AB - AIM: To analyze the lipid distribution in gastric mucosae. METHODS: Imaging mass spectrometry (MS) is a useful tool to survey the distribution of biomolecules in surgical specimens. Here we used the imaging MS apparatus named iMScope to identify the dominant molecules present in the human gastric mucosa near the fundic glands. Five gastric specimens were subjected to iMScope analysis. These specimens were also analyzed by immunohistochemistry using MUC5AC, H(+)-K(+) ATPasebeta Claudin18 antibodies. RESULTS: Three major molecules with m/z 725.5, 780.5, and 782.5 detected in the gastric mucosa were identified as sphingomyelin (SM) (d18:1/16:0), phosphatidylcholine (PC) (16:0/18:2), and PC (16:0/18:1), respectively, through MS/MS analyses. Using immunohistological staining, SM (d18:1/16:0) signals were mainly co-localized with the foveolar epithelium marker MUC5AC. In contrast, PC (16:0/18:2) signals were observed in the region testing positive for the fundic gland marker H(+)-K(+)-ATPasebeta. PC (16:0/18:1) signals were uniformly distributed throughout the mucosa. CONCLUSION: Our basic data will contribute to the studies of lipid species in physical and pathological conditions of the human stomach. PMID- 27190697 TI - Conjunctivally Applied BDNF Protects Photoreceptors from Light-Induced Damage. AB - PURPOSE: To test whether the topical eye treatment with BDNF prevents the effects of continuous light exposure (LE) in the albino rat retina. METHODS: Two groups of albino rats were used. The first group of rats received an intraocular injection of BDNF (2 MUL, 1 MUg/MUL) before LE, while the second group was treated with one single drop of BDNF (10 MUL, 12 MUg/MUL) dissolved in different types of solutions (physiological solution, the polysaccharide fraction of Tamarind gum, TSP, and sodium carboxy methyl cellulose), at the level of conjunctival fornix before LE. The level of BDNF in the retina and optic nerve was determined by enzyme-linked immunosorbent assay. We recorded the flash electroretinogram (fERG) in dark adapted rats 1 week after LE. At the end of the recording session, the retinas were removed and labeled so that the number of photoreceptors nuclear rows and thickness of the outer nuclear layer was analyzed. RESULTS: Intravitreal injection of BDNF before LE prevented fERG impairment. Different ophthalmic preparations were used for topical eye application; the TSP resulted the most suitable vehicle to increase BDNF level in the retina and optic nerve. Topical eye application with BDNF/TSP before LE partially preserved both fERG response and photoreceptors. CONCLUSIONS: Topical eye treatment with BDNF represents a suitable, noninvasive tool to increase the retinal content of BDNF up to a level capable of exerting neuroprotection toward photoreceptors injured by prolonged LE. TRANSLATIONAL RELEVANCE: A collyrium containing BDNF may serve as an effective, clinically translational treatment against retinal degeneration. PMID- 27190698 TI - Development of Visual Field Screening Procedures: A Case Study of the Octopus Perimeter. AB - PURPOSE: We develop a methodology for designing perimetric screening procedures, using Octopus perimeters as a case study. METHODS: The process has three stages: analytically determining specificity and number of presentations required for different multisampling suprathreshold schemes at a single location of the visual field, ranking visual field locations by their positive predictive value (PPV) for glaucoma, and determining a pass/fail criteria for the test. For the case study the Octopus G-program visual field test pattern is used, and a dataset of 385 glaucoma and 86 normal patients. RESULTS: Using a 1-of-3 sampling strategy at a level equal to the 95 percentile of normal observers gave the most robust specificity under the influences of false-negative responses using an average of 1.5 presentations per location. The PPV analysis gave 19 locations that completely classified our glaucomatous data. A further 9 points were added to screen for nonglaucomatous loss. The final stage found that insisting that 3 locations are missed for the screening to fail gave a simulated specificity and sensitivity of approximately 95% for unreliable responders. CONCLUSIONS: Our method gives a principled approach to choosing between the many parameters of a visual field screening procedure. We have developed a procedure for the Octopus that should terminate in less than 1 minute for normal observers with high specificity and sensitivity to glaucoma. TRANSLATIONAL RELEVANCE: Visual field screening is used in community settings and eye care practice. This study provides a principled approach to the development of such screening procedures and details a new procedure. PMID- 27190699 TI - Histopathologic Findings in the Areas of Orange Pigment Overlying Choroidal Melanomas. AB - PURPOSE: Orange pigment is an important sign of malignancy in melanocytic tumors. There is a question as to whether the pigment accumulation is inside of macrophages or retinal pigment epithelial (RPE) cells. We investigated which cells are involved with this color alteration. METHODS: We examined enucleated specimens from two patients with choroidal melanoma and dense orange pigment on fundus examination. Color fundus and fundus autofluorescence (FAF) photographs were reviewed followed by examination with fluorescent microscopy, electron microscopy, and immunohistochemistry of enucleated eyes for the specific areas corresponding to the orange pigment. RESULTS: Orange pigment was observed on color fundus photography and correlated with areas of hyperautofluorescence on FAF. Fluorescent microscopy of sections of the enucleated eyes showed autofluorescence in the RPE, which were most pronounced where there was a localized retinal detachment and reactive hyperplasia of the RPE. Immunohistochemical studies were done with keratin (OSCAR and AE1/AE3) and S-100 stained RPE cells, which still were attached to Bruch's membrane. Histiocytes present in the detached retina stained with anti-CD163 antibody and did not show autofluorescence. Electron microscopy studies of the same areas showed the presence of lipofuscin and melanolipofuscin within the clustered RPE cells. CONCLUSIONS: Orange pigment in choroidal melanocytic lesions originates from the RPE cells, rather than macrophages, and is most abundant where there is proliferation of the RPE. TRANSLATIONAL RELEVANCE: The orange pigment tumoral biomarker arises and is in the retinal pigment epithelium. PMID- 27190700 TI - Spatial Engineering of Osteochondral Tissue Constructs Through Microfluidically Directed Differentiation of Mesenchymal Stem Cells. AB - The development of tissue engineered osteochondral units has been slowed by a number of technical hurdles associated with recapitulating their heterogeneous nature ex vivo. Subsequently, numerous approaches with respect to cell sourcing, scaffolding composition, and culture media formulation have been pursued, which have led to high variability in outcomes and ultimately the lack of a consensus bioprocessing strategy. As such, the objective of this study was to standardize the design process by focusing on differentially supporting formation of cartilaginous and bony matrix by a single cell source in a spatially controlled manner within a single material system. A cell-polymer solution of bovine mesenchymal stem cells and agarose was cast against micromolds of a serpentine network and stacked to produce tissue constructs containing two independent microfluidic networks. Constructs were fluidically connected to two controlled flow loops and supplied with independently tuned differentiation parameters for chondrogenic and osteogenic induction, respectively. Constructs receiving inductive media showed differential gene expression of both chondrogenic and osteogenic markers in opposite directions along the thickness of the construct that was recapitulated at the protein level with respect to collagens I, II, and X. A control group receiving noninductive media showed homogeneous expression of these biomarkers measured in lower concentrations at both the mRNA and protein level. This work represents an important step in the rational design of engineered osteochondral units through establishment of an enabling technology for further optimization of scaffolding formulations and bioprocessing conditions toward the production of commercially viable osteochondral tissue products. PMID- 27190701 TI - Largest global shark biomass found in the northern Galapagos Islands of Darwin and Wolf. AB - Overfishing has dramatically depleted sharks and other large predatory fishes worldwide except for a few remote and/or well-protected areas. The islands of Darwin and Wolf in the far north of the Galapagos Marine Reserve (GMR) are known for their large shark abundance, making them a global scuba diving and conservation hotspot. Here we report quantitative estimates of fish abundance at Darwin and Wolf over two consecutive years using stereo-video surveys, which reveal the largest reef fish biomass ever reported (17.5 t [Formula: see text] on average), consisting largely of sharks. Despite this, the abundance of reef fishes around the GMR, such as groupers, has been severely reduced because of unsustainable fishing practices. Although Darwin and Wolf are within the GMR, they were not fully protected from fishing until March 2016. Given the ecological value and the economic importance of Darwin and Wolf for the dive tourism industry, the current protection should ensure the long-term conservation of this hotspot of unique global value. PMID- 27190703 TI - Heat shock factors in tomatoes: genome-wide identification, phylogenetic analysis and expression profiling under development and heat stress. AB - The HSF (heat shock factor) gene family contains highly conserved plant-specific transcription factors that play an important role in plant high-temperature stress responses. The present study aimed to characterize the HSF transcription factor genes in tomato (Solanum lycopersicum), which is an important vegetable crop worldwide and the model plant for fruit development studies. Twenty-six SlyHSF genes were identified in tomato, and the phylogenetic analysis showed the possible evolution profile of subgroups among in the plant kingdom. A new group O was identified that involved HSF genes in primitive plant species, like in the green algae, mosses and lycophytes. The gene structure and motifs of each SlyHSF were comprehensively analyzed. We identified orthologous, co-orthologous and paralogous HSF gene pairs in tomato, Arabidopsis and rice, and constructed a complex interaction network among these genes. The SlyHSF genes were expressed differentially in different species and at a higher level in mature fruits. The qPCR analysis was performed and showed SlyHSF genes greatly participate in plant heat tolerant pathways. Our comprehensive genome-wide analysis provided insights into the HSF gene family of tomatoes. PMID- 27190702 TI - Incorporation of an invasive plant into a native insect herbivore food web. AB - The integration of invasive species into native food webs represent multifarious dynamics of ecological and evolutionary processes. We document incorporation of Prunus serotina (black cherry) into native insect food webs. We find that P. serotina harbours a herbivore community less dense but more diverse than its native relative, P. padus (bird cherry), with similar proportions of specialists and generalists. While herbivory on P. padus remained stable over the past century, that on P. serotina gradually doubled. We show that P. serotina may have evolved changes in investment in cyanogenic glycosides compared with its native range. In the leaf beetle Gonioctena quinquepunctata, recently shifted from native Sorbus aucuparia to P. serotina, we find divergent host preferences on Sorbus- versus Prunus-derived populations, and weak host-specific differentiation among 380 individuals genotyped for 119 SNP loci. We conclude that evolutionary processes may generate a specialized herbivore community on an invasive plant, allowing prognoses of reduced invasiveness over time. On the basis of the results presented here, we would like to caution that manual control might have the adverse effect of a slowing down of processes of adaptation, and a delay in the decline of the invasive character of P. serotina. PMID- 27190704 TI - Morphometric variation of extant platyrrhine molars: taxonomic implications for fossil platyrrhines. AB - The phylogenetic position of many fossil platyrrhines with respect to extant ones is not yet clear. Two main hypotheses have been proposed: the layered or successive radiations hypothesis suggests that Patagonian fossils are Middle Miocene stem platyrrhines lacking modern descendants, whereas the long lineage hypothesis argues for an evolutionary continuity of all fossil platyrrhines with the extant ones. Our geometric morphometric analysis of a 15 landmark-based configuration of platyrrhines' first and second lower molars suggest that morphological stasis may explain the reduced molar shape variation observed. Platyrrhine lower molar shape might be a primitive retention of the ancestral state affected by strong ecological constraints throughout the radiation of the main platyrrhine families. The Patagonian fossil specimens showed two distinct morphological patterns of lower molars, Callicebus-like and Saguinus-like, which might be the precursors of the extant forms, whereas the Middle Miocene specimens, though showing morphological resemblances with the Patagonian fossils, also displayed new, derived molar patterns, Alouatta-like and Pitheciinae-like, thereby suggesting that despite the overall morphological stasis of molars, phenotypic diversification of molar shape was already settled during the Middle Miocene. PMID- 27190705 TI - Origin of aromatase inhibitory activity via proteochemometric modeling. AB - Aromatase, the rate-limiting enzyme that catalyzes the conversion of androgen to estrogen, plays an essential role in the development of estrogen-dependent breast cancer. Side effects due to aromatase inhibitors (AIs) necessitate the pursuit of novel inhibitor candidates with high selectivity, lower toxicity and increased potency. Designing a novel therapeutic agent against aromatase could be achieved computationally by means of ligand-based and structure-based methods. For over a decade, we have utilized both approaches to design potential AIs for which quantitative structure-activity relationships and molecular docking were used to explore inhibitory mechanisms of AIs towards aromatase. However, such approaches do not consider the effects that aromatase variants have on different AIs. In this study, proteochemometrics modeling was applied to analyze the interaction space between AIs and aromatase variants as a function of their substructural and amino acid features. Good predictive performance was achieved, as rigorously verified by 10-fold cross-validation, external validation, leave-one-compound-out cross-validation, leave-one-protein-out cross-validation and Y-scrambling tests. The investigations presented herein provide important insights into the mechanisms of aromatase inhibitory activity that could aid in the design of novel potent AIs as breast cancer therapeutic agents. PMID- 27190706 TI - Screening of cytoprotectors against methotrexate-induced cytogenotoxicity from bioactive phytochemicals. AB - As a well known anti-neoplastic drug, the cytogenotoxicity of methotrexate (MTX) has received more attention in recent years. To develop a new cytoprotector to reduce the risk of second cancers caused by methotrexate, an umu test combined with a micronucleus assay was employed to estimate the cytoprotective effects of ten kinds of bioactive phytochemicals and their combinations. The results showed that allicin, proanthocyanidins, polyphenols, eleutherosides and isoflavones had higher antimutagenic activities than other phytochemicals. At the highest dose tested, the MTX genetoxicity was suppressed by 34.03%~67.12%. Of all the bioactive phytochemical combinations, the combination of grape seed proanthocyanidins and eleutherosides from Siberian ginseng as well as green tea polyphenols and eleutherosides exhibited stronger antimutagenic effects; the inhibition rate of methotrexate-induced genotoxicity separately reached 74.7 +/- 6.5% and 71.8 +/- 4.7%. Pretreatment of Kunming mice with phytochemical combinations revealed an obvious reduction in micronucleus and sperm abnormality rates following exposure to MTX (p < 0.01). Moreover, significant increases in thymus and spleen indices were observed in cytoprotector candidates in treated groups. The results indicated that bioactive phytochemicals combinations had the potential to be used as new cytoprotectors. PMID- 27190707 TI - Competitive interactions between corals and turf algae depend on coral colony form. AB - Turf algae are becoming more abundant on coral reefs worldwide, but their effects on other benthic organisms remain poorly described. To describe the general characteristics of competitive interactions between corals and turf algae, we determined the occurrence and outcomes of coral-turf algal interactions among different coral growth forms (branching, upright, massive, encrusting, plating, and solitary) on a shallow reef in Vietnam. In total, the amount of turf algal interaction, i.e., the proportion of the coral boundary directly bordering turf algae, was quantified for 1,276 coral colonies belonging to 27 genera and the putative outcome of each interaction was noted. The amount of turf algal interaction and the outcome of these interactions differed predictably among the six growth forms. Encrusting corals interacted most often with turf algae, but also competed most successfully against turf algae. The opposite was observed for branching corals, which rarely interacted with turf algae and rarely won these competitive interactions. Including all other growth forms, a positive relationship was found between the amount of competitive interactions with neighboring turf algae and the percentage of such interaction won by the coral. This growth form dependent ability to outcompete turf algae was not only observed among coral species, but also among different growth forms in morphologically plastic coral genera (Acropora, Favia, Favites, Montastrea, Montipora, Porites) illustrating the general nature of this relationship. PMID- 27190709 TI - A longitudinal study of independent scholar-published open access journals. AB - Open Access (OA) is nowadays increasingly being used as a business model for the publishing of scholarly peer reviewed journals, both by specialized OA publishing companies and major, predominantly subscription-based publishers. However, in the early days of the web OA journals were mainly founded by independent academics, who were dissatisfied with the predominant print and subscription paradigm and wanted to test the opportunities offered by the new medium. There is still an on going debate about how OA journals should be operated, and the volunteer model used by many such 'indie' journals has been proposed as a viable alternative to the model adopted by big professional publishers where publishing activities are funded by authors paying expensive article processing charges (APCs). Our longitudinal quantitative study of 250 'indie' OA journals founded prior to 2002, showed that 51% of these journals were still in operation in 2014 and that the median number of articles published per year had risen from 11 to 18 among the survivors. Of these surviving journals, only 8% had started collecting APCs. A more detailed qualitative case study of five such journals provided insights into how such journals have tried to ensure the continuity and longevity of operations. PMID- 27190708 TI - Mode of action and membrane specificity of the antimicrobial peptide snakin-2. AB - Antimicrobial peptides (AMPs) are a diverse group of short, cationic peptides which are naturally occurring molecules in the first-line defense of most living organisms. They represent promising candidates for the treatment of pathogenic microorganisms. Snakin-2 (SN2) from tomato (Solanum lycopersicum) is stabilized through six intramolecular disulphide bridges; it shows broad-spectrum antimicrobial activity against bacteria and fungi, and it agglomerates single cells prior to killing. In this study, we further characterized SN2 by providing time-kill curves and corresponding growth inhibition analysis of model organisms, such as E. coli or B. subtilis. SN2 was produced recombinantly in E. coli with thioredoxin as fusion protein, which was removed after affinity purification by proteolytic digestion. Furthermore, the target specificity of SN2 was investigated by means of hemolysis and hemagglutination assays; its effect on plant cell membranes of isolated protoplasts was investigated by microscopy. SN2 shows a non-specific pore-forming effect in all tested membranes. We suggest that SN2 could be useful as a preservative agent to protect food, pharmaceuticals, or cosmetics from decomposition by microbes. PMID- 27190710 TI - Cordycepin inhibits LPS-induced inflammatory and matrix degradation in the intervertebral disc. AB - Cordycepin is a component of the extract obtained from Cordyceps militaris and has many biological activities, including anti-cancer, anti-metastatic and anti inflammatory effects. Intervertebral disc degeneration (IDD) is a degenerative disease that is closely related to the inflammation of nucleus pulposus (NP) cells. The effect of cordycepin on NP cells in relation to inflammation and degeneration has not yet been studied. In our study, we used a rat NP cell culture and an intervertebral disc (IVD) organ culture model to examine the inhibitory effects of cordycepin on lipopolysaccharide (LPS)-induced gene expression and the production of matrix degradation enzymes (MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5) and oxidative stress-associated factors (nitric oxide and PGE2). We found a protective effect of cordycepin on NP cells and IVDs against LPS-induced matrix degradation and macrophage infiltration. In addition, western blot and luciferase assay results demonstrated that pretreatment with cordycepin significantly suppressed the LPS-induced activation of the NF-kappaB pathway. Taken together, the results of our research suggest that cordycepin could exert anti-inflammatory and anti-degenerative effects on NP cells and IVDs by inhibiting the activation of the NF-kappaB pathway. Therefore, cordycepin may be a potential treatment for IDD in the future. PMID- 27190711 TI - Utilizing immunomarking techniques to track Halyomorpha halys (Hemiptera: Pentatomidae) movement and distribution within a peach orchard. AB - In this study we focus on the invasive brown marmorated stink bug, Halyomorpha halys (Stal) (Hemiptera: Pentatomidae), which has a strong dispersal capacity and has had a significant impact on several cropping systems, including peach (Prunus persica (L.)). Management of H. halys has relied on intensive insecticide use, and thus a better understanding of its dispersal behavior may assist in developing improved management strategies. In order to investigate H. halys movement and distribution patterns within a peach orchard we applied ecologically safe, food protein markers to the trees along the orchard border (chicken egg albumin in the form of liquid egg whites) and to the trees within the orchard interior (bovine casein in the form of cow's milk). We used enzyme-linked immunosorbent assays (ELISA) to assess whether collected H. halys were "marked" with either of the two protein markers, revealing where in the orchard the bugs had visited. From the density data we determined that H. halys is a perimeter driven pest in peaches, with a significantly higher density of bugs collected along the orchard border. Interestingly, this trend is primarily driven by the distribution of male bugs. The protein marking data revealed that a small proportion of male H. halys move equally between the orchard border and interior, while a small proportion of females move predominately to the border after visiting the interior. The verification of a strong edge-effect, although potentially sex-specific, implies that H. halys displays a dispersal behavior that may also be exploited for management, which may help growers more efficiently and more effectively manage H. halys. PMID- 27190712 TI - A reappraisal of Polyptychodon (Plesiosauria) from the Cretaceous of England. AB - Pliosauridae is a globally distributed clade of aquatic predatory amniotes whose fossil record spans from the Lower Jurassic to the Upper Cretaceous. However, the knowledge of pliosaurid interrelationships remains limited. In part, this is a consequence of a few key taxa awaiting detailed reassessment. Among them, the taxon Polyptychodon is of special importance. It was established on isolated teeth from the mid-Cretaceous strata of East and South East England and subsequently associated with numerous finds of near-cosmopolitan distribution. Here the taxon is reassessed based on the original dental material from England, with special focus on a large collection of late Albian material from the Cambridge Greensand near Cambridge. The dental material is reviewed here from historical and stratigraphic perspective, described in detail, and discussed in terms of its diagnostic nature. The considerable morphological variability observed in the teeth attributed to Polyptychodon, together with a wide stratigraphic range of the ascribed material, possibly exceeding 35 Ma (early Aptian to ?middle Santonian), suggests that the taxon is based on a multispecies assemblage, possibly incorporating members of different plesiosaur clades. Due to the absence of any autapomorphic characters or unique character combinations in the original material, Polyptychodon interruptus, the type species of Polyptychodon, is considered nomen dubium. From a global perspective, Polyptychodon is viewed as a wastebasket taxon whose material originating from different localities should be reconsidered separately. PMID- 27190713 TI - Localization and segmentation of optic disc in retinal images using circular Hough transform and grow-cut algorithm. AB - Automated retinal image analysis has been emerging as an important diagnostic tool for early detection of eye-related diseases such as glaucoma and diabetic retinopathy. In this paper, we have presented a robust methodology for optic disc detection and boundary segmentation, which can be seen as the preliminary step in the development of a computer-assisted diagnostic system for glaucoma in retinal images. The proposed method is based on morphological operations, the circular Hough transform and the grow-cut algorithm. The morphological operators are used to enhance the optic disc and remove the retinal vasculature and other pathologies. The optic disc center is approximated using the circular Hough transform, and the grow-cut algorithm is employed to precisely segment the optic disc boundary. The method is quantitatively evaluated on five publicly available retinal image databases DRIVE, DIARETDB1, CHASE_DB1, DRIONS-DB, Messidor and one local Shifa Hospital Database. The method achieves an optic disc detection success rate of 100% for these databases with the exception of 99.09% and 99.25% for the DRIONS-DB, Messidor, and ONHSD databases, respectively. The optic disc boundary detection achieved an average spatial overlap of 78.6%, 85.12%, 83.23%, 85.1%, 87.93%, 80.1%, and 86.1%, respectively, for these databases. This unique method has shown significant improvement over existing methods in terms of detection and boundary extraction of the optic disc. PMID- 27190714 TI - Optimisation of DNA extraction from the crustacean Daphnia. AB - Daphnia are key model organisms for mechanistic studies of phenotypic plasticity, adaptation and microevolution, which have led to an increasing demand for genomics resources. A key step in any genomics analysis, such as high-throughput sequencing, is the availability of sufficient and high quality DNA. Although commercial kits exist to extract genomic DNA from several species, preparation of high quality DNA from Daphnia spp. and other chitinous species can be challenging. Here, we optimise methods for tissue homogenisation, DNA extraction and quantification customised for different downstream analyses (e.g., LC-MS/MS, Hiseq, mate pair sequencing or Nanopore). We demonstrate that if Daphnia magna are homogenised as whole animals (including the carapace), absorbance-based DNA quantification methods significantly over-estimate the amount of DNA, resulting in using insufficient starting material for experiments, such as preparation of sequencing libraries. This is attributed to the high refractive index of chitin in Daphnia's carapace at 260 nm. Therefore, unless the carapace is removed by overnight proteinase digestion, the extracted DNA should be quantified with fluorescence-based methods. However, overnight proteinase digestion will result in partial fragmentation of DNA therefore the prepared DNA is not suitable for downstream methods that require high molecular weight DNA, such as PacBio, mate pair sequencing and Nanopore. In conclusion, we found that the MasterPure DNA purification kit, coupled with grinding of frozen tissue, is the best method for extraction of high molecular weight DNA as long as the extracted DNA is quantified with fluorescence-based methods. This method generated high yield and high molecular weight DNA (3.10 +/- 0.63 ng/ug dry mass, fragments >60 kb), free of organic contaminants (phenol, chloroform) and is suitable for large number of downstream analyses. PMID- 27190715 TI - High nonpublication rate from publication professionals hinders evidence-based publication practices. AB - Background. The need for timely, ethical, and high-quality reporting of clinical trial results has seen a rise in demand for publication professionals. These publication experts, who are not ghostwriters, work with leading medical researchers and funders around the world to plan and prepare thousands of publications each year. Despite the involvement of publication professionals in an increasing number of peer-reviewed publications, especially those that affect patient care, there is limited evidence-based guidance in the peer-reviewed literature on their publication practices. Similar to the push for editors and the peer-review community to conduct and publish research on publication ethics and the peer-review process, the International Society for Medical Publication Professionals (ISMPP) has encouraged members to conduct and publish research on publication planning and practices. Our primary objective was to investigate the publication rate of research presented at ISMPP Annual Meetings. Methods. ISMPP Annual Meeting abstract lists (April 2009-April 2014) were searched in November 2014 and data were extracted into a pilot-tested spreadsheet. MEDLINE was searched in December 2014 to determine the publication rate (calculated as the % of presented abstracts published as full papers in peer-reviewed journals). Data were analyzed using the Cochran-Armitage trend test (significance: P < .05) by an independent academic statistician. Results. From 2009 to 2014, there were 220 abstracts submitted, 185 accepted, and 164 presented. There were four corresponding publications (publication rate 2.4%). Over time, ISMPP's abstract acceptance rate (overall: 84.1%) did not change, but the number of abstracts presented increased significantly (P = .02). Most abstracts were presented as posters (81.1%) and most research was observational (72.6%). Most researchers came from the US (78.0%), followed by Europe (17.7%), and the Asia-Pacific region (11.2%). Discussion. Research presented at ISMPP Annual Meetings has rarely been published in peer-reviewed journals. The high rate of nonpublication by publication professionals has now been quantified and is of concern. Publication professionals should do more to contribute to evidence-based publication practices, including, and especially, their own. Unless the barriers to publication are identified and addressed, the practices of publication professionals, which affect thousands of peer-reviewed publications each year, will remain hidden and unproven. PMID- 27190716 TI - The Anaphase-Promoting Complex (APC) ubiquitin ligase affects chemosensory behavior in C. elegans. AB - The regulation of fundamental aspects of neurobiological function has been linked to the ubiquitin signaling system (USS), which regulates the degradation and activity of proteins and is catalyzed by E1, E2, and E3 enzymes. The Anaphase Promoting Complex (APC) is a multi-subunit E3 ubiquitin ligase that controls diverse developmental and signaling processes in post-mitotic neurons; however, potential roles for the APC in sensory function have yet to be explored. In this study, we examined the effect of the APC ubiquitin ligase on chemosensation in Caenorhabditis elegans by testing chemotaxis to the volatile odorants, diacetyl, pyrazine, and isoamyl alcohol, to which wild-type worms are attracted. Animals with loss of function mutations in either of two alleles (g48 and ye143) of the gene encoding the APC subunit EMB-27 APC6 showed increased chemotaxis towards diacetyl and pyrazine, odorants sensed by AWA neurons, but exhibited normal chemotaxis to isoamyl alcohol, which is sensed by AWC neurons. The statistically significant increase in chemotaxis in the emb-27 APC6 mutants suggests that the APC inhibits AWA-mediated chemosensation in C. elegans. Increased chemotaxis to pyrazine was also seen with mutants lacking another essential APC subunit, MAT-2 APC1; however, mat-2 APC1 mutants exhibited wild type responses to diacetyl. The difference in responsiveness of these two APC subunit mutants may be due to differential strength of these hypomorphic alleles or may indicate the presence of functional sub-complexes of the APC at work in this process. These findings are the first evidence for APC-mediated regulation of chemosensation and lay the groundwork for further studies aimed at identifying the expression levels, function, and targets of the APC in specific sensory neurons. Because of the similarity between human and C. elegans nervous systems, the role of the APC in sensory neurons may also advance our understanding of human sensory function and disease. PMID- 27190717 TI - Advertisement call and genetic structure conservatism: good news for an endangered Neotropical frog. AB - BACKGROUND: Many amphibian species are negatively affected by habitat change due to anthropogenic activities. Populations distributed over modified landscapes may be subject to local extinction or may be relegated to the remaining-likely isolated and possibly degraded-patches of available habitat. Isolation without gene flow could lead to variability in phenotypic traits owing to differences in local selective pressures such as environmental structure, microclimate, or site specific species assemblages. METHODS: Here, we tested the microevolution hypothesis by evaluating the acoustic parameters of 349 advertisement calls from 15 males from six populations of the endangered amphibian species Proceratophrys moratoi. In addition, we analyzed the genetic distances among populations and the genetic diversity with a haplotype network analysis. We performed cluster analysis on acoustic data based on the Bray-Curtis index of similarity, using the UPGMA method. We correlated acoustic dissimilarities (calculated by Euclidean distance) with geographical and genetic distances among populations. RESULTS: Spectral traits of the advertisement call of P. moratoi presented lower coefficients of variation than did temporal traits, both within and among males. Cluster analyses placed individuals without congruence in population or geographical distance, but recovered the species topology in relation to sister species. The genetic distance among populations was low; it did not exceed 0.4% for the most distant populations, and was not correlated with acoustic distance. DISCUSSION: Both acoustic features and genetic sequences are highly conserved, suggesting that populations could be connected by recent migrations, and that they are subject to stabilizing selective forces. Although further studies are required, these findings add to a growing body of literature suggesting that this species would be a good candidate for a reintroduction program without negative effects on communication or genetic impact. PMID- 27190719 TI - Genome-scale investigation of phenotypically distinct but nearly clonal Trichoderma strains. AB - Biological control agents (BCA) are beneficial organisms that are applied to protect plants from pests. Many fungi of the genus Trichoderma are successful BCAs but the underlying mechanisms are not yet fully understood. Trichoderma cf. atroviride strain LU132 is a remarkably effective BCA compared to T. cf. atroviride strain LU140 but these strains were found to be highly similar at the DNA sequence level. This unusual combination of phenotypic variability and high DNA sequence similarity between separately isolated strains prompted us to undertake a genome comparison study in order to identify DNA polymorphisms. We further investigated if the polymorphisms had functional effects on the phenotypes. The two strains were clearly identified as individuals, exhibiting different growth rates, conidiation and metabolism. Superior pathogen control demonstrated by LU132 depended on its faster growth, which is a prerequisite for successful distribution and competition. Genome sequencing identified only one non-synonymous single nucleotide polymorphism (SNP) between the strains. Based on this SNP, we successfully designed and validated an RFLP protocol that can be used to differentiate LU132 from LU140 and other Trichoderma strains. This SNP changed the amino acid sequence of SERF, encoded by the previously undescribed single copy gene "small EDRK-rich factor" (serf). A deletion of serf in the two strains did not lead to identical phenotypes, suggesting that, in addition to the single functional SNP between the nearly clonal Trichoderma cf. atroviride strains, other non-genomic factors contribute to their phenotypic variation. This finding is significant as it shows that genomics is an extremely useful but not exhaustive tool for the study of biocontrol complexity and for strain typing. PMID- 27190718 TI - The genome and transcriptome of Phalaenopsis yield insights into floral organ development and flowering regulation. AB - The Phalaenopsis orchid is an important potted flower of high economic value around the world. We report the 3.1 Gb draft genome assembly of an important winter flowering Phalaenopsis 'KHM190' cultivar. We generated 89.5 Gb RNA-seq and 113 million sRNA-seq reads to use these data to identify 41,153 protein-coding genes and 188 miRNA families. We also generated a draft genome for Phalaenopsis pulcherrima 'B8802,' a summer flowering species, via resequencing. Comparison of genome data between the two Phalaenopsis cultivars allowed the identification of 691,532 single-nucleotide polymorphisms. In this study, we reveal that the key role of PhAGL6b in the regulation of labellum organ development involves alternative splicing in the big lip mutant. Petal or sepal overexpressing PhAGL6b leads to the conversion into a lip-like structure. We also discovered that the gibberellin pathway that regulates the expression of flowering time genes during the reproductive phase change is induced by cool temperature. Our work thus depicted a valuable resource for the flowering control, flower architecture development, and breeding of the Phalaenopsis orchids. PMID- 27190720 TI - The first hominin from the early Pleistocene paleocave of Haasgat, South Africa. AB - Haasgat is a primate-rich fossil locality in the northeastern part of the Fossil Hominid Sites of South Africa UNESCO World Heritage Site. Here we report the first hominin identified from Haasgat, a partial maxillary molar (HGT 500), that was recovered from an ex situ calcified sediment block sampled from the locality. The in situ fossil bearing deposits of the Haasgat paleokarstic deposits are estimated to date to slightly older than 1.95 Ma based on magnetobiostratigraphy. This places the hominin specimen at a critical time period in South Africa that marks the last occurrence of Australopithecus around 1.98 Ma and the first evidence of Paranthropus and Homo in the region between ~2.0 and 1.8 Ma. A comprehensive morphological evaluation of the Haasgat hominin molar was conducted against the current South African catalogue of hominin dental remains and imaging analyses using micro-CT, electron and confocal microscopy. The preserved occlusal morphology is most similar to Australopithecus africanus or early Homo specimens but different from Paranthropus. Occlusal linear enamel thickness measured from micro-CT scans provides an average of ~2.0 mm consistent with Australopithecus and early Homo. Analysis of the enamel microstructure suggests an estimated periodicity of 7-9 days. Hunter-Schreger bands appear long and straight as in some Paranthropus, but contrast with this genus in the short shape of the striae of Retzius. Taken together, these data suggests that the maxillary fragment recovered from Haasgat best fits within the Australopithecus-early Homo hypodigms to the exclusion of the genus Paranthropus. At ~1.95 Ma this specimen would either represent another example of late occurring Australopithecus or one of the earliest examples of Homo in the region. While the identification of this first hominin specimen from Haasgat is not unexpected given the composition of other South African penecontemporaneous site deposits, it represents one of the few hominin localities in the topographically-distinct northern World Heritage Site. When coupled with the substantial differences in the mammalian faunal communities between the northern localities (e.g., Haasgat, Gondolin) and well-sampled Bloubank Valley sites (e.g., Sterkfontein, Swartkrans, Kromdraai), the recovery of the HGT 500 specimen highlights the potential for further research at the Haasgat locality for understanding the distribution and interactions of hominin populations across the landscape, ecosystems and fossil mammalian communities of early Pleistocene South Africa. Such contextual data from sites like Haasgat is critical for understanding the transition in hominin representation at ~2 Ma sites in the region from Australopithecus to Paranthropus and early Homo. PMID- 27190722 TI - Relationship between triterpenoid anticancer drug resistance, autophagy, and caspase-1 in adult T-cell leukemia. AB - We previously reported that the inflammasome inhibitor cucurbitacin D (CuD) induces apoptosis in human leukemia cell lines. Here, we investigated the effects of CuD and a B-cell lymphoma extra-large (Bcl-xL) inhibitor on autophagy in peripheral blood lymphocytes (PBL) isolated from adult T-cell leukemia (ATL) patients. CuD induced PBL cell death in patients but not in healthy donors. This effect was not significantly inhibited by treatment with rapamycin or 3 methyladenine (3-MA). The Bcl-xL inhibitor Z36 induced death in primary cells from ATL patients including that induced by CuD treatment, effects that were partly inhibited by 3-MA. Similarly, cell death induced by the steroid prednisolone was enhanced in the presence of Z36. A western blot analysis revealed that Z36 also promoted CuD-induced poly(ADP ribose) polymerase cleavage. Interestingly, the effects of CuD and Z36 were attenuated in primary ATL patient cells obtained upon recurrence after umbilical cord blood transplantation, as compared to those obtained before chemotherapy. Furthermore, cells from this patient expressed a high level of caspase-1, and treatment with caspase-1 inhibitor-enhanced CuD-induced cell death. Taken together, these results suggest that rescue from resistance to steroid drugs can enhance chemotherapy, and that caspase-1 is a good marker for drug resistance in ATL patients. PMID- 27190721 TI - Neuromuscular interaction is required for neurotrophins-mediated locomotor recovery following treadmill training in rat spinal cord injury. AB - Recent results have shown that exercise training promotes the recovery of injured rat distal spinal cords, but are still unclear about the function of skeletal muscle in this process. Herein, rats with incomplete thoracic (T10) spinal cord injuries (SCI) with a dual spinal lesion model were subjected to four weeks of treadmill training and then were treated with complete spinal transection at T8. We found that treadmill training allowed the retention of hind limb motor function after incomplete SCI, even with a heavy load after complete spinal transection. Moreover, treadmill training alleviated the secondary injury in distal lumbar spinal motor neurons, and enhanced BDNF/TrkB expression in the lumbar spinal cord. To discover the influence of skeletal muscle contractile activity on motor function and gene expression, we adopted botulinum toxin A (BTX A) to block the neuromuscular activity of the rat gastrocnemius muscle. BTX-A treatment inhibited the effects of treadmill training on motor function and BDNF/TrKB expression. These results indicated that treadmill training through the skeletal muscle-motor nerve-spinal cord retrograde pathway regulated neuralplasticity in the mammalian central nervous system, which induced the expression of related neurotrophins and promoted motor function recovery. PMID- 27190723 TI - Opinions regarding skin ageing in the elderly inhabitants of Bialystok, Poland. AB - Skin diseases constitute an essential health and aesthetic problem in the elderly. The aim of the study was to evaluate the knowledge of the elderly residents of public nursing homes and participants of the University of the Third Age in Bialystok, Poland surrounding the factors influencing skin ageing, the awareness of skin conditions in agening skin, and the impact of skin ageing on the volunteers. The study was performed from April to June 2015 in Bialystok, in two groups: among 100 public nursing home residents (PNH) and 100 members of University of the Third Age (U3A), (all over 60 years old). The study made use of a diagnostic survey conducted via a questionnaire prepared by the authors. Nearly half of those surveyed (42.5%; n = 85) sunbathed in the past, while 28.0% (n = 56) of those surveyed now take part in this type of leisure activity. More than half of respondents (53.0%; n = 106) protected their skin using special protective preparations. A majority of Bialystok inhabitants surveyed (80.5%; n = 161) noticed the features of skin ageing. They reported birthmarks, fungal infections and bedsores as the main skin problems of the old age. Nearly half (40%) of respondents assessed their knowledge as average and 26.0% as poor. The study showed some statistical differences in the knowledge and awareness between the residents of public nursing homes and the students of the University of the Third Age, e.g., the use of the Internet by the U3A group for finding out information. There is a desire to receive education in the field of the agening skin conditions/diseases among the elderly because their level of knowledge is relatively poor. Education of seniors in this area can increase their awareness of the basic principles of skin care and prevention marking of skin ageing. The benefits of greater knowledge of seniors about the conditions of agening skin can help reduce the medical burden and reduce the incidence on certain skin diseases. Furthermore, there is a need for educating of the younger population on the factors of skin ageing to prevent certain skin conditions as they become older. Seniors should be professionally educated by qualified specialists; for example, dermatologists or cosmeticians, so that the information they receive is in line with evidence-based medicine. PMID- 27190724 TI - PhySortR: a fast, flexible tool for sorting phylogenetic trees in R. AB - A frequent bottleneck in interpreting phylogenomic output is the need to screen often thousands of trees for features of interest, particularly robust clades of specific taxa, as evidence of monophyletic relationship and/or reticulated evolution. Here we present PhySortR, a fast, flexible R package for classifying phylogenetic trees. Unlike existing utilities, PhySortR allows for identification of both exclusive and non-exclusive clades uniting the target taxa based on tip labels (i.e., leaves) on a tree, with customisable options to assess clades within the context of the whole tree. Using simulated and empirical datasets, we demonstrate the potential and scalability of PhySortR in analysis of thousands of phylogenetic trees without a priori assumption of tree-rooting, and in yielding readily interpretable trees that unambiguously satisfy the query. PhySortR is a command-line tool that is freely available and easily automatable. PMID- 27190725 TI - Dural-Based Cavernoma of the Posterior Cranial Fossa Mimicking a Meningioma: A Case Report. AB - Cavernous angiomas usually occur in the parenchyma of both the supra and infratentorial compartments. At times, they can both clinically and radiologically mimic other dural-based lesions. We present a case of a patient with chronic occipital headaches, initially thought to have a meningioma, but proven to be a cavernoma with histological analysis. PMID- 27190726 TI - Intravitreal Injection-Induced Migraine Headaches. AB - A case of migraine headache triggered by intravitreal injection, and aborted by retrobulbar injection, is reported. To date, migraine and related cephalgia have not been reported after intravitreal injection. Ophthalmologists and neurologists should be aware of this potential sequela of a very common procedure. PMID- 27190727 TI - The Treatment of Adult Bipolar Disorder with Aripiprazole: A Systematic Review. AB - Bipolar disorder is characterized by exacerbations of opposite mood polarity, ranging from manic to major depressive episodes. In the current nosological system of the Diagnostic and Statistical Manual - 5(th) edition (DSM-5), it is conceptualized as a spectrum disorder consisting of bipolar disorder type I, bipolar disorder type II, cyclothymic disorder, and bipolar disorder not otherwise specified. Treatment of all phases of this disorder is primarily with mood stabilizers, but many patients either show resistance to the conventional mood stabilizing medications or are intolerant to their side-effects. In this setting, second-generation antipsychotics have gained prominence as many bipolar subjects who are otherwise treatment refractory show response to these agents. Aripiprazole is a novel antipsychotic initially approved for the treatment of schizophrenia but soon found to be effective in bipolar disorder. This drug is well studied, as randomized controlled trials have been conducted in various phases of bipolar disorders. Aripiprazole exhibits the pharmacodynamic properties of partial agonism, functional selectivity, and serotonin-dopamine activity modulation - the new exemplars in the treatment of major psychiatric disorders. It is the first among a new series of psychotropic medications, which now also include brexpiprazole and cariprazine. The current review summarizes the data from controlled trials regarding the efficacy and safety of aripiprazole in adult bipolar patients. On the basis of this evidence, aripiprazole is found to be efficacious in the treatment and prophylaxis of manic and mixed episodes but has no effectiveness in acute and recurrent bipolar depression. PMID- 27190728 TI - Atypical Presentation of C. Difficile Infection: Report of a Case with Literature Review. AB - Clostridium difficile (C. difficile) is a gram-positive, obligate, anaerobic spore-forming bacillus first reported by Hall and O'Toole in 1935. It occurs mostly after antibiotic use and invariably presents with watery diarrhea. We describe an atypical presentation of C. difficile in a 64-year-old Caucasian female who presented to the our emergency department with abdominal pain, nausea, and vomiting for one day. A complete blood count revealed leukocytosis 30 x 10(9)/L and a subsequent computed tomography (CT) scan of the abdomen and the pelvis, showed fluid filled small bowel loops consistent with enteritis. Her presentation was unusual for lack of diarrhea, the hallmark of C. difficile infection. She was admitted and treated with oral vancomycin. The polymerase chain reaction (PCR) value in the stool for C. difficile was positive. The patient responded very well: her abdominal pain resolved and leukocyte count normalized after a few doses of vancomycin (125 mg po qid). The patient's progress was followed in our clinic for the last three months. PMID- 27190729 TI - Sonography in Hypotension and Cardiac Arrest (SHoC): Rates of Abnormal Findings in Undifferentiated Hypotension and During Cardiac Arrest as a Basis for Consensus on a Hierarchical Point of Care Ultrasound Protocol. AB - INTRODUCTION: Point of care ultrasound (PoCUS) has become an established tool in the initial management of patients with undifferentiated hypotension. Current established protocols (RUSH and ACES) were developed by expert user opinion, rather than objective, prospective data. PoCUS also provides invaluable information during resuscitation efforts in cardiac arrest by determining presence/absence of cardiac activity and identifying reversible causes such as pericardial tamponade. There is no agreed guideline on how to safely and effectively incorporate PoCUS into the advanced cardiac life support (ACLS) algorithm. We wished to report disease incidence as a basis to develop a hierarchical approach to PoCUS in hypotension and during cardiac arrest. METHODS: We summarized the recorded incidence of PoCUS findings from the initial cohort during the interim analysis of two prospective studies. We propose that this will form the basis for developing a modified Delphi approach incorporating this data to obtain the input of a panel of international experts associated with five professional organizations led by the International Federation of Emergency Medicine (IFEM). The modified Delphi tool will be developed to reach an international consensus on how to integrate PoCUS for hypotensive emergency department patients as well as into cardiac arrest algorithms. RESULTS: Rates of abnormal PoCUS findings from 151 patients with undifferentiated hypotension included left ventricular dynamic changes (43%), IVC abnormalities (27%), pericardial effusion (16%), and pleural fluid (8%). Abdominal pathology was rare (fluid 5%, AAA 2%). During cardiac arrest there were no pericardial effusions, however abnormalities of ventricular contraction (45%) and valvular motion (39%) were common among the 43 patients included. CONCLUSIONS: A prospectively collected disease incidence-based hierarchy of scanning can be developed based on the reported findings. This will inform an international consensus process towards the development of proposed SHoC protocols for hypotension and cardiac arrest, comprised of the stepwise clinical-indication based approach of Core, Supplementary, and Additional PoCUS views. We hope that such a protocol would be structured in a way that enables the clinician to only perform views that are clinically indicated, which limits exposure to the frequent incidental positive findings that accompany the current "one size fits all" standard protocols. PMID- 27190730 TI - Intravascular Biphasic Synovial Sarcoma: The Beneficial Role of Adjuvant Treatment Approach in the Pre-metastatic Stage. AB - Synovial sarcoma (SS) is a high-grade, rare variant of soft tissue sarcoma (STS). The biphasic subtype is less common than the monophasic subtype. SS is very common around joint cavities in the extremities, but can be present elsewhere in the body. Tumor staging and therapeutic management are usually clear for a localized disease, but the proper management at the metastatic stage can be unclear. According to the literature, the histologic presence of an SS tumor thrombus affects tumor staging, making it unclear whether the tumor stage corresponds to localized or metastatic disease. An intravascular SS tumor exhibiting high metastatic potential is a rare finding that warrants thorough investigation. A 49-year-old woman presented with a biphasic SS intravascular tumor of the left inguinal area with femoral vessels involvement. Ten cases of intravascular SS have been reported in the literature and contain little information regarding the proper management of a local metastatic disease. Ours is a rare case of SS with an intravascular tumor occupying the femoral-iliac vein (as seen in metastatic disease) that has been treated as a local disease with a multidisciplinary therapeutic approach. As a result, our patient has been disease free for two years and, during that time, has achieved an acceptable quality of life. We discuss the pertinent clinical findings of this rare tumor and review the literature of tumor thrombus by SS. We also present the multidisciplinary therapeutic approach realized and the history of this disease. PMID- 27190731 TI - The Impact of Preoperative Depression and Health State on Quality-of-Life Outcomes after Anterior Cervical Diskectomy and Fusion. AB - Study Design Retrospective cohort study. Objective We sought to assess the predictive value of preoperative depression and health state on 1-year quality-of life outcomes after anterior cervical diskectomy and fusion (ACDF). Methods We analyzed 106 patients who underwent ACDF. All patients had either bilateral or unilateral cervical radiculopathy. Preoperative and 1-year postoperative health outcomes were assessed based on the visual analog scale, Pain Disability Questionnaire (PDQ), Patient Health Questionnaire (PHQ-9), and EuroQol-5 Dimensions (EQ-5D) questionnaire. Univariable and multivariate regression analyses were performed to assess for preoperative predictors of 1-year change in health status according to the EQ-5D. Results Compared with preoperative health states, the ACDF cohort showed statistically significant improved PDQ (78.5 versus 57.9), PHQ-9 (9.7 versus 5.3), and EQ-5D (0.55 versus 0.68) scores at 1 year postoperatively and surpassed the minimum clinically important difference for the EQ-5D of 0.1 units (all p <= 0.01). Multivariate linear regression indicated that anxiolytic use and higher EQ-5D preoperative scores were associated with less 1-year postoperative improvement in health status. Although not statistically significant, clinically important effects of preoperative depression, as measured by the PHQ-9, were observed on postoperative QOL outcome (-0.006, 95% confidence interval -0.014 to 0.001). Conclusions Of patients who undergo ACDF with similar preoperative QOL health states, those with a greater degree of depression may have lower improvements in postoperative QOL compared with those with less depression. Patients with anxiety and better preoperative health states also attain less 1-year QOL improvements. PMID- 27190732 TI - The Burden of Clostridium difficile after Cervical Spine Surgery. AB - Study Design Retrospective database analysis. Objective The purpose of this study is to investigate incidence, comorbidities, and impact on health care resources of Clostridium difficile infection after cervical spine surgery. Methods A total of 1,602,130 cervical spine surgeries from the Nationwide Inpatient Sample database from 2002 to 2011 were included. Patients were included for study based on International Classification of Diseases Ninth Revision, Clinical Modification procedural codes for cervical spine surgery for degenerative spine diagnoses. Baseline patient characteristics were determined. Multivariable analyses assessed factors associated with increased incidence of C. difficile and risk of mortality. Results Incidence of C. difficile infection in postoperative cervical spine surgery hospitalizations is 0.08%, significantly increased since 2002 (p < 0.0001). The odds of postoperative C. difficile infection were significantly increased in patients with comorbidities such as congestive heart failure, renal failure, and perivascular disease. Circumferential cervical fusion (odds ratio [OR] = 2.93, p < 0.0001) increased the likelihood of developing C. difficile infection after degenerative cervical spine surgery. C. difficile infection after cervical spine surgery results in extended length of stay (p < 0.0001) and increased hospital costs (p < 0.0001). Mortality rate in patients who develop C. difficile after cervical spine surgery is nearly 8% versus 0.19% otherwise (p < 0.0001). Moreover, multivariate analysis revealed C. difficile to be a significant predictor of inpatient mortality (OR = 3.99, p < 0.0001). Conclusions C. difficile increases the risk of in-hospital mortality and costs approximately $6,830,695 per year to manage in patients undergoing elective cervical spine surgery. Patients with comorbidities such as renal failure or congestive heart failure have increased probability of developing infection after surgery. Accepted antibiotic guidelines in this population must be followed to decrease the risk of developing postoperative C. difficile colitis. PMID- 27190733 TI - Accuracy of Percutaneous Pedicle Screw Insertion Technique with Conventional Dual Fluoroscopy Units and a Retrospective Comparative Study Based on Surgeon Experience. AB - Study Design Retrospective comparative study. Objective To evaluate the accuracy of percutaneous pedicle screw (PPS) placement and intraoperative imaging time using dual fluoroscopy units and their differences between surgeons with more versus less experience. Methods One hundred sixty-one patients who underwent lumbar fusion surgery were divided into two groups, A (n = 74) and B (n = 87), based on the performing surgeon's experience. The accuracy of PPS placement and radiation time for PPS insertion were compared. PPSs were inserted with classic technique under the assistance of dual fluoroscopy units placed in two planes. The breach definition of PPS misplacement was based on postoperative computed tomography (grade I: no breach; grade II: <2 mm; grade III: <=2 to <4 mm). Results Of 658 PPSs, only 21 screws were misplaced. The breach rates of groups A and B were 3.3% (grade II: 3.4%, grade III: 0%) and 3.1% (grade II: 2.6%, grade III: 0.6%; p = 0.91). One patient in grade III misplacement had a transient symptom of leg numbness. Median radiation exposure time during PPS insertion was 25 seconds and 51 seconds, respectively (p < 0.01). Conclusions Without using an expensive imaging support system, the classic technique of PPS insertion using dual fluoroscopy units in the lumbar and sacral spine is fairly accurate and provides good clinical outcomes, even among surgeons lacking experience. PMID- 27190734 TI - The Thoracolumbar AOSpine Injury Score. AB - Study Design Survey of 100 worldwide spine surgeons. Objective To develop a spine injury score for the AOSpine Thoracolumbar Spine Injury Classification System. Methods Each respondent was asked to numerically grade the severity of each variable of the AOSpine Thoracolumbar Spine Injury Classification System. Using the results, as well as limited input from the AOSpine Trauma Knowledge Forum, the Thoracolumbar AOSpine Injury Score was developed. Results Beginning with 1 point for A1, groups A, B, and C were consecutively awarded an additional point (A1, 1 point; A2, 2 points; A3, 3 points); however, because of a significant increase in the severity between A3 and A4 and because the severity of A4 and B1 was similar, both A4 and B1 were awarded 5 points. An uneven stepwise increase in severity moving from N0 to N4, with a substantial increase in severity between N2 (nerve root injury with radicular symptoms) and N3 (incomplete spinal cord injury) injuries, was identified. Hence, each grade of neurologic injury was progressively given an additional point starting with 0 points for N0, and the substantial difference in severity between N2 and N3 injuries was recognized by elevating N3 to 4 points. Finally, 1 point was awarded to the M1 modifier (indeterminate posterolateral ligamentous complex injury). Conclusion The Thoracolumbar AOSpine Injury Score is an easy-to-use, data-driven metric that will allow for the development of a surgical algorithm to accompany the AOSpine Thoracolumbar Spine Injury Classification System. PMID- 27190735 TI - Biomechanical Analysis of the Proximal Adjacent Segment after Multilevel Instrumentation of the Thoracic Spine: Do Hooks Ease the Transition? AB - Study Design Biomechanical cadaveric study. Objective Clinical studies indicate that using less-rigid fixation techniques in place of the standard all-pedicle screw construct when correcting for scoliosis may reduce the incidence of proximal junctional kyphosis and improve patient outcomes. The purpose of this study is to investigate whether there is a biomechanical advantage to using supralaminar hooks in place of pedicle screws at the upper-instrumented vertebrae in a multilevel thoracic construct. Methods T7-T12 spines were biomechanically tested: (1) intact; (2) following a two-level pedicles screw fusion from T9 to T11; and after proximal extension of the fusion to T8-T9 with (3) bilateral supra laminar hooks, (4) a unilateral hook + unilateral screw hybrid, or (5) bilateral pedicle screws. Specimens were nondestructively loaded while three-dimensional kinematics and intradiscal pressure at the supra-adjacent level were recorded. Results Supra-adjacent hypermobility was reduced when bilateral hooks were used in place of pedicle screws at the upper-instrumented level, with statistically significant differences in lateral bending and torsion (p < 0.05 and p < 0.001, respectively). Disk pressures in the supra-adjacent segment were not statistically different among top-off techniques. Conclusions The use of supralaminar hooks at the top of a multilevel posterior fusion construct reduces the stress at the proximal uninstrumented motion segment. Although further data is needed to provide a definitive link to the clinical occurrence of PJK, this in vitro study demonstrates the potential benefit of "easing" the transition between the stiff instrumented spine and the flexible native spine and is the first to demonstrate these results with laminar hooks. PMID- 27190736 TI - Screw Placement Accuracy and Outcomes Following O-Arm-Navigated Atlantoaxial Fusion: A Feasibility Study. AB - Study Design Case series of seven patients. Objective C2 stabilization can be challenging due to the complex anatomy of the upper cervical vertebrae. We describe seven cases of C1-C2 fusion using intraoperative navigation to aid in the screw placement at the atlantoaxial (C1-C2) junction. Methods Between 2011 and 2014, seven patients underwent posterior atlantoaxial fusion using intraoperative frameless stereotactic O-arm Surgical Imaging and StealthStation Surgical Navigation System (Medtronic, Inc., Minneapolis, Minnesota, United States). Outcome measures included screw accuracy, neurologic status, radiation dosing, and surgical complications. Results Four patients had fusion at C1-C2 only, and in the remaining three, fixation extended down to C3 due to anatomical considerations for screw placement recognized on intraoperative imaging. Out of 30 screws placed, all demonstrated minimal divergence from desired placement in either C1 lateral mass, C2 pedicle, or C3 lateral mass. No neurovascular compromise was seen following the use of intraoperative guided screw placement. The average radiation dosing due to intraoperative imaging was 39.0 mGy. All patients were followed for a minimum of 12 months. All patients went on to solid fusion. Conclusion C1-C2 fusion using computed tomography-guided navigation is a safe and effective way to treat atlantoaxial instability. Intraoperative neuronavigation allows for high accuracy of screw placement, limits complications by sparing injury to the critical structures in the upper cervical spine, and can help surgeons make intraoperative decisions regarding complex pathology. PMID- 27190737 TI - Cervical Myeloradiculopathy due to Ossification of the Posterior Longitudinal Ligament with versus without Diffuse Idiopathic Spinal Hyperostosis. AB - Study Design Retrospective study. Objectives Assess demographics, ossification characteristics, surgical outcomes, and complications in patients with both diffuse idiopathic spinal hyperostosis (DISH) and ossification of the posterior longitudinal ligament (OPLL) compared with patients who only have OPLL. Methods Clinical charts and radiographs of all patients treated surgically from February 2004 to July 2012 for cervical myeloradiculopathy due to DISH with OPLL or OPLL alone were reviewed retrospectively. All patients were observed for a minimum of 1 year. Pre- and postoperative Nurick grades were assessed for all patients. Results Forty-nine patients underwent surgical treatment for cervical myeloradiculopathy due to OPLL, and 8 also had DISH (average 58.9 years, range 37 to 70). The DISH with OPLL group had a significantly higher proportion of subjects with diabetes mellitus (50 versus 9.8% in the OPLL-only group). Everyone in the DISH with OPLL group had continuous or mixed-type OPLL, whereas 78% of patients in the OPLL-only group had primarily segmental type. Operative treatments for patients in the DISH with OPLL group included laminoplasty, anterior decompression and fusion, and posterior laminectomy with fusion. By Nurick grade, 5 patients improved and 3 showed no change. Conclusion Patients with both DISH and OPLL had a higher prevalence of diabetes mellitus and either continuous or mixed-type OPLL classifications. Surgical outcomes were mostly satisfactory; there was no aggravation of symptoms after surgery during the follow up period. PMID- 27190738 TI - Cadaveric Spinal Surgery Simulation: A Comparison of Cadaver Types. AB - Study Design Single-blinded study. Objective To assess the suitability of three types of cadaver for simulating pedicle screw insertion and establish if there is an ideal. Methods Three types of cadaver-Thiel-embalmed, Crosado-embalmed, and formaldehyde-embalmed-were draped and the spines exposed. Experienced surgeons were asked to place pedicle screws in each cadaver and give written questionnaire feedback using a modified Likert scale. Soft tissue and bony properties were assessed, along with the role of simulation in spinal surgery training. Results The Thiel cadaver rated highest for soft tissue feel and appearance with a median score of 6 for both (range 2 to 7). The Crosado cadaver rated highest for bony feel, with a median score of 6 (range 2 to 7). The formaldehyde cadaver rated lowest for all categories with median scores of 2, 2.5, and 3.5, respectively. All surgeons felt pedicle screw insertion should be learned in a simulated setting using human cadavers. Conclusion Thiel and Crosado cadavers both offered lifelike simulation of pedicle screw insertion, with each having advantages depending on whether the focus is on soft tissue approach or technical aspects of bony screw insertion. Both cadaver types offer the advantage of long life span, unlike fresh frozen tissue, which means cadavers can be used multiple times, thus reducing the costs. PMID- 27190739 TI - Correlations of Cervical Sagittal Alignment before and after Occipitocervical Fusion. AB - Study Design Retrospective radiographic study. Objective To investigate changes and correlations of cervical sagittal alignment including T1 slope before and after occipitocervical corrective surgery. We also investigated the relevance for preoperative planning. Methods We conducted a retrospective radiographic analysis of 27 patients who underwent surgery for occipitocervical deformity. There were 7 men and 20 women with a mean age of 56.0 years. Mean follow-up was 68.0 months (range 24 to 120). The radiographic parameters measured before surgery and at final follow-up included McGregor slope, T1 slope, occipito (O)-C2 angle, O-C7 angle, and C2-C7 angle. Pearson correlation coefficient was used to examine the correlation between the radiographic parameters. Results There was a stronger positive correlation between the T1 slope and the O-C7 angle both preoperatively and postoperatively (r = 0.72 and r = 0.83, respectively) than between the T1 slope and the C2-C7 angle (r = 0.60 and r = 0.76, respectively). The O-C2 angle and C2-C7 angle had inverse correlations to each other both pre- and postoperatively (r = - 0.50 and -0.45). McGregor slope and T1 slope did not significantly change postoperatively at final follow-up. Increase in O-C2 angle after surgery (mean change, 10.7 degrees) inversely correlated with decrease in postoperative C2-C7 angle (mean change, 12.2 degrees). As result of these complementary changes, O-C7 angle did not statistically change. Conclusions Our results suggest that the O-C7 angle is regulated by T1 slope and the corresponding O-C7 angle is divided into the O-C2 and C2-C7 angles, which have inverse correlation to each other and then maintain McGregor slope (horizontal gaze). PMID- 27190740 TI - Spinolaminar Line Test as a Screening Tool for C1 Stenosis. AB - Study Design Retrospective cohort. Objective To clarify the sensitivity of C3-C2 spinolaminar line test as a screening tool for the stenosis of C1 space available for the cord (SAC). Methods Spine clinic records from April 2005 to August 2011 were reviewed. The C1 SAC was measured on lateral radiographs, and the relative positions between a C1 posterior arch and the C3-C2 spinolaminar line were examined and considered "positive" when the C1 ring lay ventral to the line. Computed tomography (CT) scans and magnetic resonance imaging (MRI) were utilized to measure precise diameters of C1 and C2 SAC and to check the existence of spinal cord compression. Results Four hundred eighty-seven patients were included in this study. There were 246 men and 241 women, with an average age of 53 years (range: 18 to 86). The mean SAC at C1 on radiographs was 21.2 mm (range: 13.5 to 28.2). Twenty-one patients (4.3%) were positive for the spinolaminar line test; all of these patients had C1 SAC of 19.4 mm or less. Eight patients (1.6%) had C1 SAC smaller than C2 on CT examination; all of these patients had a positive spinolaminar test, with high sensitivity (100%) and specificity (97%). MRI analysis revealed that two of the eight patients with a smaller C1 SAC had spinal cord compression at the C1 level. Conclusion Although spinal cord compression at the level of atlas without instability is a rare condition, the spinolaminar line can be used as a screening of C1 stenosis. PMID- 27190741 TI - Solitary C1 Posterior Fixation for Unstable Isolated Atlas Fractures: Case Report and Systematic Review of the Literature. AB - Study Design A systematic review of the literature. Objectives To review the published results to date of motion-preserving direct reconstruction of C1 ring fractures with combined coronal plane displacement of at least 7 mm (rule of Spence) and so at risk for Dickman type I or II disruption of the transverse atlantal ligament (TAL). Methods A structured literature review prompted by successful management of a typical case. Results To date only 65 such cases are reported and follow-up is almost uniformly short. Although reported clinical success is uniform, the case mix is heterogenous and confirmation/classification of ligamentous injury at baseline is often lacking. Conclusions Direct C1 stabilization shows promise as a "more selective" option in managing displaced atlas fractures with probable TAL disruption but cannot yet be recommended as a practice standard. Prospective clinical studies are indicated and should be structured so as to differentiate between Dickman type I and type II injuries of the TAL. PMID- 27190742 TI - Upper Cervical Epidural Abscess in Clinical Practice: Diagnosis and Management. AB - Study Design Narrative review. Objective Upper cervical epidural abscess (UCEA) is a rare surgical emergency. Despite increasing incidence, uncertainty remains as to how it should initially be managed. Risk factors for UCEA include immunocompromised hosts, diabetes mellitus, and intravenous drug use. Our objective is to provide a comprehensive overview of the literature including the history, clinical manifestations, diagnosis, and management of UCEA. Methods Using PubMed, studies published prior to 2015 were analyzed. We used the keywords "Upper cervical epidural abscess," "C1 osteomyelitis," "C2 osteomyelitis," "C1 epidural abscess," "C2 epidural abscess." We excluded cases with tuberculosis. Results The review addresses epidemiology, etiology, imaging, microbiology, and diagnosis of this condition. We also address the nonoperative and operative management options and the relative indications for each as reviewed in the literature. Conclusion A high index of suspicion is required to diagnose this rare condition with magnetic resonance imaging being the imaging modality of choice. There has been a shift toward surgical management of this condition in recent times, with favorable outcomes. PMID- 27190743 TI - The Effects of Obesity on Spine Surgery: A Systematic Review of the Literature. AB - Study Design Literature review. Objective The aim of this literature review is to examine the effects of obesity on postoperative complications and functional outcomes after spine surgery. Methods A review of the relevant literature examining the effects of obesity and spine surgery was conducted using PubMed, Google Scholar, and Cochrane databases. Results Obesity contributes to disk degeneration and low back pain and potentially increases the risk of developing operative pathology. Obese patients undergoing spine surgery have a higher risk of developing postoperative complications, particularly surgical site infection and venous thromboembolism. Though functional outcomes in this population may not mirror the general population, the treatment effect associated with surgery is at least equivalent if not better in obese individuals. This reduction is primarily due to worse outcomes associated with nonoperative treatment in the obese population. Conclusion Obese individuals represent a unique patient population with respect to nonoperative treatment, postoperative complication rates, and functional outcomes. However, given the equivalent or greater treatment effect of surgery, this comorbidity should not prohibit obese patients from undergoing operative intervention. Future investigations in this area should attempt to develop strategies to minimize complications and improve outcomes in obese individuals and also examine the role of controlled weight loss preoperatively to mitigate these risks. PMID- 27190745 TI - Some remarks on b-(E.A)-property in b-metric spaces. AB - In this paper we consider, discuss, improve and generalize recent b-(E.A) property results for mappings in b-metric spaces established by Ozturk and Turkoglu (J Nonlinear Convex Anal 16(10):2059-2066, 2015). Thus, all our results are with much shorter proofs. One example is given to support the result. PMID- 27190744 TI - A Comparison of Magnetic Resonance Imaging Muscle Fat Content in the Lumbar Paraspinal Muscles with Patient-Reported Outcome Measures in Patients with Lumbar Degenerative Disk Disease and Focal Disk Prolapse. AB - Study Design Retrospective study. Objectives To assess the fatty atrophy of the lumbar paraspinal muscles (LPMs) as determined using magnetic resonance imaging in patients with lumbar degenerative disk disease (DDD) and focal disk herniation and to determine if fatty atrophy is associated with patient-reported outcome measures (PROMS). Methods One hundred sixty-five patients with lumbar DDD were identified from a PROMS database of >1,500 patients. These patients were divided into two study groups: DDD alone (n = 58) and DDD with disk herniation (n = 107). A grid was randomly applied to the axial scans at the L3-L4, L4-L5, and L5-S1 levels. The muscle-to-fat ratio of the LPMs was recorded and compared with PROMS data. Subcutaneous fat thickness at each level was also measured. Results This study found no difference in the muscle-to-fat ratio between the DDD and disk herniation groups. There was no association between the muscle-to-fat ratio and PROMS data in either group. There was significantly more subcutaneous fat at all levels in the DDD group as compared with the disk prolapse group. In DDD and disk prolapses, subcutaneous fat was thicker in women (p = 0.013 and 0.001). In patients with DDD, more subcutaneous fat was associated with disability (p < 0.001). Muscle content of erector spinae and multifidus negatively correlated with increasing age in both groups at the L3-L4 level. Conclusions Muscle fat content in the LPM does not appear to relate to PROMS. Muscle content decreases with age. Those with low back pain (DDD) have greater subcutaneous fat thickness. PMID- 27190747 TI - Usability evaluation of mobile applications using ISO 9241 and ISO 25062 standards. AB - This paper presents an empirical study based on a set of measures to evaluate the usability of mobile applications running on different mobile operating systems, including Android, iOS and Symbian. The aim is to evaluate empirically a framework that we have developed on the use of the Software Quality Standard ISO 9126 in mobile environments, especially the usability characteristic. To do that, 32 users had participated in the experiment and we have used ISO 25062 and ISO 9241 standards for objective measures by working with two widely used mobile applications: Google Apps and Google Maps. The QUIS 7.0 questionnaire have been used to collect measures assessing the users' level of satisfaction when using these two mobile applications. By analyzing the results we highlighted a set of mobile usability issues that are related to the hardware as well as to the software and that need to be taken into account by designers and developers in order to improve the usability of mobile applications. PMID- 27190746 TI - The inhibitory activity of cocoa phenolic extract against pro-inflammatory mediators secretion induced by lipopolysaccharide in RAW 264.7 cells. AB - Cocoa is a rich source of polyphenols that has been traditionally used as the treatment of several types of inflammation related disease. The response to inflammation comprises the consecutive release of mediators and the enlistment of circulating leukocytes, such as macrophages. Currently, Cocoa-derived polyphenolics have shown anti-inflammatory effects in vivo, but the therapeutic benefits in vitro remain unclear. Therefore, in this study, the effect of cocoa polyphenolic extract (CPE) on RAW 264.7 macrophage cells sensitized by lipopolysaccharide as in vitro inflammatory model was investigated. The anti inflammatory activity of CPE was assessed by measuring its ability to inhibit the pro-inflammatory enzyme 5-lipoxygenase (5-LOX) and the pro-inflammatory mediators prostaglandin E2 (PGE2), reactive oxygen species (ROS), nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha). The results show that CPE significantly inhibits 5-LOX activity (p < 0.01). In addition, CPE dose-dependently suppressed the production of PGE2, ROS, NO and TNF-alpha in RAW 264.7 cells. These data suggest that CPE may be used for the treatment of inflammation and it's related diseases. PMID- 27190748 TI - Lessening the adverse effect of the semivariogram model selection on an interpolative survey using kriging technique. AB - OBJECTIVE: Many parameters in environmental, scientific and human sciences investigations need to be interpolated. Geostatistics, with its structural analysis step, is widely used for this purpose. This precious step that evaluates data correlation and dependency is performed thanks to semivariogram. However, an incorrect choice of a semivariogram model can skew all the prediction results. The main objectives of this paper are (1) to simply illustrate the influence of the choice of an inappropriate semivariogram model and (2) to show how a best fitted model can be selected. This may lessen the adverse effect of the semivariogram model selection on an interpolation survey using kriging technique. METHODS: The influence of the semivariogram model selection is highlighted and illustrated by thematic maps drawn using four different models (Gaussian, magnetic, spherical and exponential). Then, a guideline to select the most suitable model, using mean error (ME), mean square error (MSE), root mean square error (RMSE), average standard error (ASE), and root mean square standardized error (RMSSE), is proposed. RESULTS: The choice of a semivariogram model seriously influences the results of a kriging survey at both endpoints and amplitude of the range of the estimated values. However, the direction of variation of the interpolated values is independent of the semivariogram model: different semivariogram models (with the same characteristics) produce different thematic maps but, the areas of minimum and maximum values remain unchanged. Yet, the suitable model can be selected by means of ME, MSE, RMSE, ASE and RMSSE. CONCLUSION: The present article illustrates how the use of an inappropriate semivariogram model can seriously distort the results of an evaluation, assessment or prediction survey. To avoid such an inconveniency, a methodical approach based on the computation and analysis of ME, RMSE, ASE, RMSSE and MSE is proposed. PMID- 27190749 TI - The q-Laguerre matrix polynomials. AB - The Laguerre polynomials have been extended to Laguerre matrix polynomials by means of studying certain second-order matrix differential equation. In this paper, certain second-order matrix q-difference equation is investigated and solved. Its solution gives a generalized of the q-Laguerre polynomials in matrix variable. Four generating functions of this matrix polynomials are investigated. Two slightly different explicit forms are introduced. Three-term recurrence relation, Rodrigues-type formula and the q-orthogonality property are given. PMID- 27190750 TI - Clinical value of preoperative serum CA 19-9 and CA 125 levels in predicting the resectability of hilar cholangiocarcinoma. AB - BACKGROUND: To examine the predictive value of tumor markers for evaluating tumor resectability in patients with hilar cholangiocarcinoma and to explore the prognostic effect of various preoperative factors on resectability in patients with potentially resectable tumors. Patients with potentially resectable tumors judged by radiologic examination were included. The receiver operating characteristic (ROC) analysis was conducted to evaluate serum carbohydrate antigenic determinant 19-9 (CA 19-9), carbohydrate antigen 125 (CA 125) and carcino embryonie antigen levels on tumor resectability. Univariate and multivariate logistic regression models were also conducted to analysis the correlation of preoperative factors with resectability. RESULTS: In patients with normal bilirubin levels, ROC curve analysis calculated the ideal CA 19-9 cut-off value of 203.96 U/ml in prediction of resectability, with a sensitivity of 83.7 %, specificity of 80 %, positive predictive value of 91.1 % and negative predictive value of 66.7 %. Meanwhile, the optimal cut-off value for CA 125 to predict resectability was 25.905 U/ml (sensitivity, 78.6 %; specificity, 67.5 %). In a multivariate logistic regression model, tumor size <=3 cm (OR 4.149, 95 % CI 1.326-12.981, P = 0.015), preoperative CA 19-9 level <=200 U/ml (OR 20.324, 95 % CI 6.509-63.467, P < 0.001), preoperative CA 125 levels <=26 U/ml (OR 8.209, 95 % CI 2.624-25.677, P < 0.001) were independent determinants of resectability in patients diagnosed as hilar cholangiocarcinoma. CONCLUSIONS: Preoperative CA 19-9 and CA 125 levels predict resectability in patients with radiological resectable hilar cholangiocarcinoma. Increased preoperative CA 19-9 levels and CA 125 levels are associated with poor resectability rate. PMID- 27190752 TI - Comparative study on the customization of natural language interfaces to databases. AB - In the last decades the popularity of natural language interfaces to databases (NLIDBs) has increased, because in many cases information obtained from them is used for making important business decisions. Unfortunately, the complexity of their customization by database administrators make them difficult to use. In order for a NLIDB to obtain a high percentage of correctly translated queries, it is necessary that it is correctly customized for the database to be queried. In most cases the performance reported in NLIDB literature is the highest possible; i.e., the performance obtained when the interfaces were customized by the implementers. However, for end users it is more important the performance that the interface can yield when the NLIDB is customized by someone different from the implementers. Unfortunately, there exist very few articles that report NLIDB performance when the NLIDBs are not customized by the implementers. This article presents a semantically-enriched data dictionary (which permits solving many of the problems that occur when translating from natural language to SQL) and an experiment in which two groups of undergraduate students customized our NLIDB and English language frontend (ELF), considered one of the best available commercial NLIDBs. The experimental results show that, when customized by the first group, our NLIDB obtained a 44.69 % of correctly answered queries and ELF 11.83 % for the ATIS database, and when customized by the second group, our NLIDB attained 77.05 % and ELF 13.48 %. The performance attained by our NLIDB, when customized by ourselves was 90 %. PMID- 27190751 TI - Effect of dietary histamine supplementation on growth, digestive enzyme activities and morphology of intestine and hepatopancreas in the Chinese mitten crab Eriocheir sinensis. AB - A 28-days feeding experiment was conducted to investigate the effect of histamine on digestive physiology of the Chinese mitten crab, Eriocheir sinensis. Four experimental diets were supplemented with histamine at 0, 1, 2, 4 g/kg. Histamine supplementation had no effect on growth. The activities of digestive enzyme decreased significantly at first (days 7 and 14) (p < 0.05) and then increased or finally slightly recovered in the hepatopancreas and intestinal tract on the 28th day. Tryptase and amylase activities were inhibited significantly in each histamine-treated group on day 7 as compared to the control (p < 0.05). On day 7, 14 and 28, tryptase mRNA relative expression in the histamine treatments correlated positively with the histamine concentration (p < 0.05). Histopathologic analyses showed serious alterations in hepatopancreas, moderate alterations in the hindgut and intestinal bulb, and no alterations in the midgut. In hepatopancreas, low levels (1 g/kg) of histamine caused an increase in the number of B-cells. High levels (4 g/kg) of histamine increased the number of R cells, which were also highly vacuolized. In extreme cases, the basal lamina was detached from the tubule. In the intestinal bulb and hindgut, high levels of histamine (4 g/kg) decreased the density of reserve inclusion cells. Thus, this indicated that histamine had dose-dependent effect on the activity of digestive enzymes and the morphology of the intestine and hepatopancreas. PMID- 27190753 TI - Algorithm for finding partitionings of hard variants of boolean satisfiability problem with application to inversion of some cryptographic functions. AB - In this paper we propose an approach for constructing partitionings of hard variants of the Boolean satisfiability problem (SAT). Such partitionings can be used for solving corresponding SAT instances in parallel. For the same SAT instance one can construct different partitionings, each of them is a set of simplified versions of the original SAT instance. The effectiveness of an arbitrary partitioning is determined by the total time of solving of all SAT instances from it. We suggest the approach, based on the Monte Carlo method, for estimating time of processing of an arbitrary partitioning. With each partitioning we associate a point in the special finite search space. The estimation of effectiveness of the particular partitioning is the value of predictive function in the corresponding point of this space. The problem of search for an effective partitioning can be formulated as a problem of optimization of the predictive function. We use metaheuristic algorithms (simulated annealing and tabu search) to move from point to point in the search space. In our computational experiments we found partitionings for SAT instances encoding problems of inversion of some cryptographic functions. Several of these SAT instances with realistic predicted solving time were successfully solved on a computing cluster and in the volunteer computing project SAT@home. The solving time agrees well with estimations obtained by the proposed method. PMID- 27190755 TI - Bernese periacetabular osteotomy for hip dysplasia: Surgical technique and indications. AB - For young, active patients with healthy hip cartilage, pelvic osteotomy is a surgical option in to address hip pain and to improve mechanical loading conditions related to dysplasia. Hip dysplasia may lead to arthrosis at an early age due to poor coverage of the femoral head and abnormal loading of the joint articulation. In patients with symptomatic dysplasia and closed triradiate cartilage (generally over age 10), including adolescents and young adults (generally up to around age 40), the Bernese periacetabular osteotomy (PAO) is a durable technique for addressing underlying structural deformity. The PAO involves a modified Smith-Petersen approach. Advantages of the Bernese osteotomy include preservation of the weight-bearing posterior column of the hemi-pelvis, preservation of the acetabular blood supply, maintenance of the hip abductor musculature, and the ability to effect powerful deformity correction about an ideal center of rotation. There is an increasing body of evidence that preservation of the native hip can be improved through pelvic osteotomy. In contrast to hip osteotomy and joint preservation, the role of total hip arthroplasty in young, active patients with correctable hip deformity remains controversial. Moreover, the durability of hip replacement in young patients is inherently limited. Pelvic osteotomy should be considered the preferred method to address correctable structural deformity of the hip in the young, active patient with developmental dysplasia. The Bernese PAO is technically demanding, yet offers reproducible results with good long-term survivorship in carefully selected patients with preserved cartilage and the ability to meet the demands of rehabilitation. PMID- 27190756 TI - Controversial role of arthroscopic meniscectomy of the knee: A review. AB - The role of arthroscopic partial meniscectomy (APM) in reducing pain and improving function in patients with meniscal tears remains controversial. Five recent high-quality randomized controlled trials (RCTs) compared non-operative management of meniscal tears to APM, with four showing no difference and one demonstrating superiority of APM. In this review, we examined the strengths and weaknesses of each of these RCTs, with particular attention to the occurrence of inadvertent biases. We also completed a quantitative analysis that compares treatment successes in each treatment arm, considering crossovers as treatment failures. Our analysis revealed that each study was an excellent attempt to compare APM with non-surgical treatment but suffered from selection, performance, detection, and/or transfer biases that reduce confidence in its conclusions. While the RCT remains the methodological gold standard for establishing treatment efficacy, the use of an RCT design does not in itself ensure internal or external validity. Furthermore, under our alternative analysis of treatment successes, two studies had significantly more treatment successes in the APM arm than the non operative arm although original intention-to-treat analyses showed no difference between these two groups. Crossovers remain an important problem in surgical trials with no perfect analytical solution. With the studies available at present, no conclusion can be drawn concerning the optimal treatment modality for meniscal tears. Further work that minimizes significant biases and crossovers and incorporates sub-group and cost-benefit analyses may clarify therapeutic indications. PMID- 27190754 TI - Management of metal-on-metal hip implant patients: Who, when and how to revise? AB - The debate on how best to manage patients with metal-on-metal (MOM) hip implants continues. With over 1 million patients affected worldwide, the impact is far reaching. The majority of the aggressive failures of MOM hip implants have been dealt with by revision hip surgery, leaving patients with a much more indolent pattern of failure of devices that have been in situ for more than 10 years. The longer-term outcome for such patients remains unknown, and much debate exists on how best to manage these patients. Regulatory guidance is available but remains open to interpretation due to the lack of current evidence and long-term studies. Metal ion thresholds for concern have been suggested at 7 ppb for hip resurfacing arthroplasty and below this level for large diameter total hip arthroplasties. Soft tissue changes including pseudotumours and muscle atrophy have been shown to progress, but this is not consistent. New advanced imaging techniques are helping to diagnose complications with metal hips and the reasons for failure, however these are not widely available. This has led to some centres to tackle difficult cases through multidisciplinary collaboration, for both surgical management decisions and also follow-up decisions. We summarise current evidence and consider who is at risk, when revision should be undertaken and how patients should be managed. PMID- 27190757 TI - Resection and reconstruction of pelvic and extremity soft tissue sarcomas with major vascular involvement: Current concepts. AB - Soft tissue sarcoma accounts for approximately 1% of all cancers diagnosed annually in the United States. When these rare malignant mesodermal tumours arise in the pelvis and extremities, they may potentially encase or invade large calibre vascular structures. This presents a major challenge in terms of safe excision while also leaving acceptable surgical margins. In recent times, the trend has been towards limb salvage with vascular reconstruction in preference to amputation. Newer orthopaedic and vascular reconstructive techniques including both synthetic and autogenous graft reconstruction have made complex limb-salvage surgery feasible. Despite this, limb-salvage surgery with concomitant vascular reconstruction remains associated with higher rates of post-operative complications including infection and amputation. In this review we describe the initial presentation and investigation of patients presenting with soft tissue sarcomas in the pelvis and extremities, which involve vascular structures. We further discuss the key surgical reconstructive principles and techniques available for the management of these complex tumours, drawn from our institution's experience as a national tertiary referral sarcoma service. PMID- 27190758 TI - Valgus osteotomy for nonunion and neglected neck of femur fractures. AB - Nonunion neck of femur can be a difficult problem to treat, particularly in the young, and is associated with high complication rates of avascular necrosis due to the precarious blood supply and poor biomechanics. The various treatment options that have been described can be broadly divided according to the aim of improving either biology or biomechanics. Surgeries aimed at improving the biology, such as vascularized fibula grafting, have good success rates but require high levels of expertise and substantial resources. A popular surgical treatment aimed at improving the biomechanics-valgus intertrochanteric osteotomy optimizes conditions for fracture healing by converting shear forces across the fracture site into compressive forces. Numerous variations of this surgical procedure have been developed and successfully applied in clinical practice. As a result, the proximal femoral orientation for obtaining a good functional outcome has evolved over the years, and the present concept of altering the proximal femoral anatomy as little as possible has arisen. This technical objective supports attaining union as well as a good functional outcome, since excessive valgus can lead to increased joint reaction forces. This review summarizes the historical and current literature on valgus intertrochanteric osteotomy treatment of nonunion neck of femur, with a focus on factors predictive of good functional outcome and potential pitfalls to be avoided as well as controversies surrounding this procedure. PMID- 27190759 TI - From Cape Town to Cambridge: Orthopaedic trauma in contrasting environments. AB - AIM: To compare the trauma experience gained by a trainee at a United Kingdom major trauma centre and a secondary level hospital in South Africa. METHODS: A profile of inpatient trauma cases during a five-week period in Addenbrooke's Hospital, Cambridge and Somerset Hospital, Cape Town was created. This was achieved by recording various parameters for each patient admitted including age, gender, injury, mechanism of injury and postal/area code. This, together with details of the departments themselves, allows a comparison of the amount and variety of orthopaedic trauma cases experienced by an individual trainee in each setting. RESULTS: The trauma profiles differed significantly. Patients in Cape Town were younger and more likely to be male. In the young, injury in Cape Town was more likely to occur due to assault or being struck by a vehicle, whilst patients in Cambridge were more likely to be injured whilst in a vehicle or in high energy falls. In older patients, trauma at both centres was almost exclusively due to mechanical falls. In a given age group, injuries at the two centres were similar, however the majority of patients admitted to Addenbrooke's were elderly, resulting in less variation in the overall injury profile. CONCLUSION: The trauma profile of a major trauma centre in the United Kingdom is less varied than that of a South African secondary centre, with significantly fewer cases per surgeon. This suggests a more varied training experience in the developing world with a greater caseload. PMID- 27190761 TI - Methicillin-resistant Staphylococcus aureus infected gluteal compartment syndrome with rhabdomyolysis in a bodybuilder. AB - Gluteal compartment syndrome (GCS) is a rare condition. We present a case of gluteal muscle strain with hematoma formation, methicillin-resistant Staphylococcus aureus (MRSA) superinfection, leading to acute GCS, rhabdomyolysis and acute kidney injury. This combination of diagnoses has not been reported in the literature. A 36-year-old Caucasian male presented with buttock pain, swelling and fever after lifting weights. Gluteal compartment pressure was markedly elevated compared with the contralateral side. Investigations revealed elevated white blood cell, erythrocyte sedimentation rate, C-reactive protein, creatine kinase, creatinine and lactic acid. Urinalysis was consistent with myoglobinuria. Magnetic resonance imaging showed increased T2 signal in the gluteus maximus and a central hematoma. Cultures taken from the emergency debridement and fasciotomy revealed MRSA. He had repeat, debridement 2 d later, and delayed primary closure 3 d after. GCS is rare and must be suspected when patients present with pain and swelling after an inciting event. They are easily diagnosed with compartment pressure monitoring. The treatment of gluteal abscess and compartment syndrome is the same and involves rapid surgical debridement. PMID- 27190762 TI - T2 relaxation time is related to liver fibrosis severity. AB - BACKGROUND: The grading of liver fibrosis relies on liver biopsy. Imaging techniques, including elastography and relaxometric, techniques have had varying success in diagnosing moderate fibrosis. The goal of this study was to determine if there is a relationship between the T2-relaxation time of hepatic parenchyma and the histologic grade of liver fibrosis in patients with hepatitis C undergoing both routine, liver MRI and liver biopsy, and to validate our methodology with phantoms and in a rat model of liver fibrosis. METHODS: This study is composed of three parts: (I) 123 patients who underwent both routine, clinical liver MRI and biopsy within a 6-month period, between July 1999 and January 2010 were enrolled in a retrospective study. MR imaging was performed at 1.5 T using dual-echo turbo-spin echo equivalent pulse sequence. T2 relaxation time of liver parenchyma in patients was calculated by mono-exponential fit of a region of interest (ROI) within the right lobe correlating to histopathologic grading (Ishak 0-6) and routine serum liver inflammation [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)]. Statistical comparison was performed using ordinary logistic and ordinal logistic regression and ANOVA comparing T2 to Ishak fibrosis without and using AST and ALT as covariates; (II) a phantom was prepared using serial dilutions of dextran coated magnetic iron oxide nanoparticles. T2 weighed imaging was performed by comparing a dual echo fast spin echo sequence to a Carr-Purcell-Meigboom-Gill (CPMG) multi echo sequence at 1.5 T. Statistical comparison was performed using a paired t test; (III) male Wistar rats receiving weekly intraperitoneal injections of phosphate buffer solution (PBS) control (n=4 rats); diethylnitrosamine (DEN) for either 5 (n=5 rats) or 8 weeks (n=4 rats) were MR imaged on a Bruker Pharmascan 4.7 T magnet with a home-built bird-cage coil. T2 was quantified by using a mono exponential fitting algorithm on multi-slice multi echo T2 weighted data. Statistical comparison was performed using ANOVA. RESULTS: (I) Histopathologic evaluation of both rat and human livers demonstrated no evidence of steatosis or hemochromatosis There was a monotonic increase in mean T2 value with increasing degree of fibrosis (control 65.4+/-2.9 ms, n=6 patients); mild (Ishak 1-2) 66.7+/ 1.9 ms (n=30); moderate (Ishak 3-4) 71.6+/-1.7 ms (n=26); severe (Ishak 5-6) 72.4+/-1.4 ms (n=61); with relatively low standard error (~2.9 ms). There was a statistically significant difference between degrees of mild (Ishak <4) vs. moderate to severe fibrosis (Ishak >4) (P=0.03) based on logistic regression of T2 and Ishak, which became insignificant (P=0.07) when using inflammatory markers as covariates. Expanding on this model using ordinal logistic regression, there was significance amongst all 4 groups comparing T2 to Ishak (P=0.01), with significance using inflammation as a covariate (P=0.03) and approaching statistical significance amongst all groups by ANOVA (P=0.07); (II) there was a monotonic increase in T2 and statistical significance (ANOVA P<0.0001) between each rat subgroup [phosphate buffer solution (PBS) 25.2+/-0.8, DEN 5-week (31.1+/ 1.5), and DEN 9-week (49.4+/-0.4) ms]; (III) the phantoms that had T2 values within the relevant range for the human liver (e.g., 20-100 ms), demonstrated no statistical difference between two point fits on turbo spin echo (TSE) data and multi-echo CPMG data (P=0.9). CONCLUSIONS: The finding of increased T2 with liver fibrosis may relate to inflammation that may be an alternative or adjunct to other noninvasive MR imaging based approaches for assessing liver fibrosis. PMID- 27190763 TI - The tumor shape changes of nasopharyngeal cancer during chemoradiotherapy: the estimated margin to cover the geometrical variation. AB - BACKGROUND: Considerable geometrical change occurs during chemoradiotherapy (CRT) course of nasopharyngeal carcinoma (NPC). This aim of this study was to quantify the volumetric and surface variability of the target volumes (TV) and to estimate the expanded margin to maintain acceptable geometrical coverage. METHODS: Twenty patients with locally advanced nasopharyngeal cancer underwent one planning CT (pCT) and six weekly repeated CT (rCT) scans during the treatment course of definitive CRT. The TV included the gross tumor volume (GTV) of the primary tumor, large (shortest diameter >3.0 cm) and small (diameter >1 cm and <=3 cm) positive neck lymph nodes, and low-risk clinical target volume (CTV_Lr) that were delineated manually on the pCT and each rCT. When comparing TV in pCT (V_pCT) and TV in rCT (V_rCT), the overlapping index (OI), Dice similarity coefficient (DSC), shortest perpendicular distance (SPD), and overall standard deviation (overall SD) were calculated to present the geometric changes. An isotropical margin was expanded outward around CTV_Lr in pCT to establish the mimic planning target volume (PTV). An OI >=0.95 was defined as acceptable geometrical coverage. RESULTS: For all TV, DSCs decreased, and the SPDs and overall SD increased with the increasing number of fractions delivered. The DSCs of all gross TV were <70% after the third week. The mean SPDs were 1.5-2.5 mm in the first week and 5.2-6.2 mm in the last week. The OI and DSC in concurrent CRT were smaller than those in the sequential therapy; and similarly the SPD and overall SD in the concurrent therapy were larger than those in the sequential one. To maintain >95% geometrical coverage, a 2-mm additional margin could maintain the coverage throughout the treatment course and a 1-mm margin could maintain the desired coverage if there is an adaptive re-planning no later than the third week of the treatment course. CONCLUSIONS: Both volumetric coverage and surface of the tumour underwent the progressive changes during the treatment course of CRT. One to two mm as the expanded margin to establish the PTV is required to maintain >95% geometrical coverage. PMID- 27190764 TI - Optic nerve head perfusion in normal eyes and eyes with glaucoma using optical coherence tomography-based microangiography. AB - BACKGROUND: To investigate the differences of perfusion in the optic nerve head (ONH) between normal and glaucomatous eyes using optical microangiography (OMAG) based optical coherence tomography (OCT) angiography technique. METHODS: One eye from each subject was scanned with a 68 kHz Cirrus 5000 HD-OCT-based OMAG prototype system centered at the ONH (Carl Zeiss Meditec Inc, Dublin, CA, USA). Microvascular images were generated from the OMAG dataset by detecting the differences in OCT signal between consecutive B-scans. The pre-laminar layer (preLC) was isolated by a semi-automatic segmentation program. En face OMAG images for preLC were generated using signals with highest blood flow signal intensity. ONH perfusion was quantified as flux, vessel area density, and normalized flux within the ONH. Standard t-tests were performed to analyze the ONH perfusion differences between normal and glaucomatous eyes. Linear regression models were constructed to analyze the correlation between ONH perfusion and other clinical measurements. RESULTS: Twenty normal and 21 glaucoma subjects were enrolled. Glaucomatous eyes had significantly lower ONH perfusion in preLC in all three perfusion metrics compared to normal eyes (P<=0.0003). Significant correlations between ONH perfusion and disease severity as well as structural changes were detected in glaucomatous eyes (P<=0.012). CONCLUSIONS: ONH perfusion detected by OMAG showed significant differences between glaucoma and normal controls and was significantly correlated with disease severity and structural defects in glaucomatous eyes. ONH perfusion measurement using OMAG may provide useful information for detection and monitoring of glaucoma. PMID- 27190760 TI - Management of lumbar zygapophysial (facet) joint pain. AB - AIM: To investigate the diagnostic validity and therapeutic value of lumbar facet joint interventions in managing chronic low back pain. METHODS: The review process applied systematic evidence-based assessment methodology of controlled trials of diagnostic validity and randomized controlled trials of therapeutic efficacy. Inclusion criteria encompassed all facet joint interventions performed in a controlled fashion. The pain relief of greater than 50% was the outcome measure for diagnostic accuracy assessment of the controlled studies with ability to perform previously painful movements, whereas, for randomized controlled therapeutic efficacy studies, the primary outcome was significant pain relief and the secondary outcome was a positive change in functional status. For the inclusion of the diagnostic controlled studies, all studies must have utilized either placebo controlled facet joint blocks or comparative local anesthetic blocks. In assessing therapeutic interventions, short-term and long-term reliefs were defined as either up to 6 mo or greater than 6 mo of relief. The literature search was extensive utilizing various types of electronic search media including PubMed from 1966 onwards, Cochrane library, National Guideline Clearinghouse, clinicaltrials.gov, along with other sources including previous systematic reviews, non-indexed journals, and abstracts until March 2015. Each manuscript included in the assessment was assessed for methodologic quality or risk of bias assessment utilizing the Quality Appraisal of Reliability Studies checklist for diagnostic interventions, and Cochrane review criteria and the Interventional Pain Management Techniques - Quality Appraisal of Reliability and Risk of Bias Assessment tool for therapeutic interventions. Evidence based on the review of the systematic assessment of controlled studies was graded utilizing a modified schema of qualitative evidence with best evidence synthesis, variable from level I to level V. RESULTS: Across all databases, 16 high quality diagnostic accuracy studies were identified. In addition, multiple studies assessed the influence of multiple factors on diagnostic validity. In contrast to diagnostic validity studies, therapeutic efficacy trials were limited to a total of 14 randomized controlled trials, assessing the efficacy of intraarticular injections, facet or zygapophysial joint nerve blocks, and radiofrequency neurotomy of the innervation of the facet joints. The evidence for the diagnostic validity of lumbar facet joint nerve blocks with at least 75% pain relief with ability to perform previously painful movements was level I, based on a range of level I to V derived from a best evidence synthesis. For therapeutic interventions, the evidence was variable from level II to III, with level II evidence for lumbar facet joint nerve blocks and radiofrequency neurotomy for long-term improvement (greater than 6 mo), and level III evidence for lumbosacral zygapophysial joint injections for short-term improvement only. CONCLUSION: This review provides significant evidence for the diagnostic validity of facet joint nerve blocks, and moderate evidence for therapeutic radiofrequency neurotomy and therapeutic facet joint nerve blocks in managing chronic low back pain. PMID- 27190765 TI - In vitro investigation of contrast flow jet timing in patient-specific intracranial aneurysms. AB - BACKGROUND: The direction and magnitude of intra-aneurysmal flow jet are significant risk factors of subarachnoid hemorrhage, and the change of flow jet during an endovascular procedure has been used for prediction of aneurysm occlusion or whether an additional flow diverter (FD) is warranted. However, evaluation of flow jets is often unreliable due to a large variation of flow jet on the digital subtraction angiograms, and this flow pattern variation may result in incorrect clinical diagnosis Therefore, factors contributing to the variation in flow jet are examined at an in vitro setting, and the findings can help us to understand the nature of flow jet and devise a better plan to quantify the aneurysmal hemodynamics accurately. METHODS: Intra-aneurysmal flows in three patient-specific aneurysms between 11 and 25 mm were investigated in vitro, and a FD was deployed in each aneurysm model. X-ray imaging of these models were performed at injection rates between 0.2 and 2 mL/s. Pulsatile blood pump and aneurysm model were imaged together to determine the timing of flow jet. RESULTS: The contrast bolus arrives at the aneurysm early at high contrast injection rates. The flow patterns with slow injection rates exhibit strong inertia that is associated with the systole flow. Flow jets arrive at the aneurysms at the peak systole when the bolus is injected at 0.2 mL/s. The contrast-to-signal ratio is the highest at the injection rate of 0.5 mL/s. Effect of flow diversion can only be assessed at an injection rate greater than 0.5 mL/s. CONCLUSIONS: Intra aneurysmal flow jet is highly dependent on the injection rate of the contrast agent. For the internal carotid artery (ICA) aneurysms, the systolic flows can be visualized at slow injection rates (<0.5 mL/s), while the diastolic flow jets are visible at higher injection rates (>1 mL/s). Dependence of flow jet on the contrast injection rate has serious clinical implications and needs to be considered during diagnostic procedures; a protocol with a consistent injection rate is highly recommended. PMID- 27190766 TI - Quantitative 3D breast magnetic resonance imaging fibroglandular tissue analysis and correlation with qualitative assessments: a feasibility study. AB - BACKGROUND: The amount of fibroglandular tissue (FGT) has been linked to breast cancer risk based on mammographic density studies. Currently, the qualitative assessment of FGT on mammogram (MG) and magnetic resonance imaging (MRI) is prone to intra and inter-observer variability. The purpose of this study is to develop an objective quantitative FGT measurement tool for breast MRI that could provide significant clinical value. METHODS: An IRB approved study was performed. Sixty breast MRI cases with qualitative assessment of mammographic breast density and MRI FGT were randomly selected for quantitative analysis from routine breast MRIs performed at our institution from 1/2013 to 12/2014. Blinded to the qualitative data, whole breast and FGT contours were delineated on T1-weighted pre contrast sagittal images using an in-house, proprietary segmentation algorithm which combines the region-based active contours and a level set approach. FGT (%) was calculated by: [segmented volume of FGT (mm(3))/(segmented volume of whole breast (mm(3))] *100. Statistical correlation analysis was performed between quantified FGT (%) on MRI and qualitative assessments of mammographic breast density and MRI FGT. RESULTS: There was a significant positive correlation between quantitative MRI FGT assessment and qualitative MRI FGT (r=0.809, n=60, P<0.001) and mammographic density assessment (r=0.805, n=60, P<0.001). There was a significant correlation between qualitative MRI FGT assessment and mammographic density assessment (r=0.725, n=60, P<0.001). The four qualitative assessment categories of FGT correlated with the calculated mean quantitative FGT (%) of 4.61% (95% CI, 0-12.3%), 8.74% (7.3-10.2%), 18.1% (15.1-21.1%), 37.4% (29.5-45.3%). CONCLUSIONS: Quantitative measures of FGT (%) were computed with data derived from breast MRI and correlated significantly with conventional qualitative assessments. This quantitative technique may prove to be a valuable tool in clinical use by providing computer generated standardized measurements with limited intra or inter-observer variability. PMID- 27190767 TI - A higher aneurysmal subarachnoid hemorrhage incidence in women prior to menopause: a retrospective analysis of 4,895 cases from eight hospitals in China. AB - BACKGROUND: Subarachnoid hemorrhage (SAH) from a ruptured cerebral aneurysm is a devastating disease. Despite the risk factors, including hypertension, cigarette smoking and alcohol use, are more common in men, aneurysmal SAH belongs to a few diseases which the incidence is higher in women than in men. Sex hormones, especially estrogen, might be protective against this condition. Hormone replacement therapy (HRT) seems to be associated with a reduced risk for aneurysmal SAH. This study aims to know the prevalence of aneurysmal SAH of men and women at different ages. METHODS: The age and gender information of 4,895 case of aneurysmal SAH (3,016 females, 1,879 males) were collected retrospectively from eight institutions in mainland China. The prevalence of aneurysmal SAH of men and women at different ages was analyzed. RESULTS: The data showed women had a higher incidence of aneurysmal SAH than men starting at late thirties, and men might have a higher incidence of aneurysmal SAH than women only before 37-year-old. CONCLUSIONS: Menopause may not be the only dominant factor causing higher incidence of aneurysmal SAH in women than in men. PMID- 27190768 TI - Acute pancreatitis with gradient echo T2*-weighted magnetic resonance imaging. AB - BACKGROUND: To study gradient recalled echo (GRE) T2*-weighted imaging (T2*WI) for normal pancreas and acute pancreatitis (AP). METHODS: Fifty-one patients without any pancreatic disorders (control group) and 117 patients with AP were recruited. T2* values derived from T2*WI of the pancreas were measured for the two groups. The severity of AP was graded by the magnetic resonance severity index (MRSI) and the Acute Physiology and Chronic Healthy Evaluation II (APACHE II) scoring system. Logistic regression was used to analyze the relationship between the T2* values and AP severity. The usefulness of the T2* value for diagnosing AP and the relationship between the T2* values and the severity of AP were analyzed. RESULTS: On GRE-T2*WI, the normal pancreas showed a well-marinated and consistently homogeneous isointensity. Edematous AP, as well as the non necrotic area in necrotizing AP, showed ill-defined but homogeneous signal intensity. AP with pancreatic hemorrhage showed a decreased T2* value and a signal loss on the signal decay curve. The T2* value of pancreas in the AP group was higher than that of the control group (t=-8.20, P<0.05). The T2* value tended to increase along with the increase in MRSI scores but not with the APACHE II scores (P>0.05). AP was associated with a one standard deviation increment in the T2* value (OR =1.37; 95% CI: 1.216-1.532). CONCLUSIONS: T2*WI demonstrates a few characteristics of the normal pancreas and AP, which could potentially be helpful for detecting hemorrhage, and contributes to diagnosing AP and its severity. PMID- 27190769 TI - Breath-hold black blood quantitative T1rho imaging of liver using single shot fast spin echo acquisition. AB - BACKGROUND: Liver fibrosis is a key feature in most chronic liver diseases. T1rho magnetic resonance imaging is a potentially important technique for noninvasive diagnosis, severity grading, and therapy monitoring of liver fibrosis. However, it remains challenging to perform robust T1rho quantification of liver on human subjects. One major reason is that the presence of rich blood signal in liver can cause artificially high T1rho measurement and makes T1rho quantification susceptible to motion. METHODS: A pulse sequence based on single shot fast/turbo spin echo (SSFSE/SSTSE) acquisition, with theoretical analysis and simulation based on the extended phase graph (EPG) algorithm, was presented for breath-hold single slice quantitative T1rho imaging of liver with suppression of blood signal. The pulse sequence was evaluated in human subjects at 3.0 T with 500 Hz spinlock frequency and time-of-spinlock (TSL) 0, 10, 30 and 50 ms. RESULTS: Human scan demonstrated that the entire T1rho data sets with four spinlock time can be acquired within a single breath-hold of 10 seconds with black blood effect. T1rho quantification with suppression of blood signal results in significantly reduced T1rho value of liver compared to the results without blood suppression. CONCLUSIONS: A signal-to-noise ratio (SNR) efficient pulse sequence was reported for T1rho quantification of liver. The black blood effect, together with a short breath-hold, mitigates the risk of quantification errors as would occur in the conventional methods. PMID- 27190770 TI - Optical coherence tomography based microangiography findings in hydroxychloroquine toxicity. AB - Optical coherence tomography based microangiography (OMAG) is a new, non-invasive imaging modality capable of providing three dimentional (3D) retinal and choroidal microvascular maps without a need for exogenous dye. In this study, we evaluated the retinal and choroidal microvascular architecture of the macula in a patient with hydroxychloroquine (HCQ) toxicity using OMAG. Detailed microvascular information of the retina and the underlying choroid showed loss of parafoveal outer retinal vasculature with sparing of the central fovea vasculature. PMID- 27190771 TI - The imaging of osteomyelitis. AB - Osteomyelitis is an important cause of morbidity and mortality in children and adults. Imaging plays a crucial role in establishing a timely diagnosis and guiding early management, with the aim of reducing long-term complications. Recognition of the imaging features of osteomyelitis requires a good understanding of its pathogenesis. In this review, the key imaging findings in osteomyelitis are correlated with the underlying pathological processes. There is a particular emphasis on magnetic resonance imaging (MRI), which is the best available imaging modality owing to its high sensitivity for detecting early osteomyelitis, excellent anatomical detail and superior soft tissue resolution. However, other modalities such as nuclear medicine and computed tomography (CT) are also useful in many clinical contexts, and will also be described in this review. PMID- 27190773 TI - Antisynthetase syndrome: a case report. AB - The case is about a 48-year-old man with one week history of progressively worsening shortness of breath and reduced exercise tolerance. Laboratory investigations revealed raised ESR, creatine kinase (CK) and positive anti aminoacyl-transfer RNA synthetase. High resolution computed tomography (HRCT) chest showed prominent mediastinal lymph nodes and scattered lung nodules. These findings along with clinical features and investigations confirmed the diagnosis of antisynthetase syndrome (ASS). The radiological investigations proved to be the key step in diagnosis and management of this case. PMID- 27190774 TI - Intrathoracic gastric perforation secondary to corrosive ingestion: a rare complication. AB - This case report describes a rare and serious case of acid ingestion in a 50-year old man who developed necrosis and perforation of gastric fundus and diaphragm with extension of air and fluid collection in the thorax. To the best of our knowledge, this complication has not been described so far in the literature. PMID- 27190775 TI - Synchronous Kimura lesions at two different sites-a diagnostic dilemma! AB - Kimura disease (KD) is a rare, chronic, benign inflammatory disorder of unknown etiology mimicking neoplastic disease and is characterized by multiple subcutaneous nodules and masses, primarily in the cervical region, accompanied by peripheral eosinophilia and lymphadenopathy. A 35-year-old male presented with a 2-year history of swelling in the right preauricular region and right thigh. Investigations showed a peripheral eosinophilia. CT of cervical region revealed parotid neoplasm and a fine needle aspiration was inconclusive. The thigh swelling felt vascular and a CT angiogram was done which revealed a diffuse vascular lesion. A superficial parotidectomy and an excision of the right thigh swelling were done. Histopathologies of both specimens were reported to have features suggestive of KD. The patient was evaluated for systemic manifestations and found to have no abnormalities. The patient has been disease free on follow up after 2 years. This case is being presented for the rarity of its incidence and the nature of its presentation. PMID- 27190776 TI - Pigmented villonodular synovitis mimics metastases on fluorine 18 fluorodeoxyglucose position emission tomography-computed tomography. AB - Pigmented villonodular synovitis (PVNS) is a benign joint disease best characterized on magnetic resonance imaging (MRI). The role of fluorine 18 fluorodeoxyglucose ((18)F-FDG) position emission tomography-computed tomography (PET-CT) in the diagnosis or characterization remains unclear. PVNS displays as a focal FDG avid lesion, which can masquerade as a metastatic lesion, on PET-CET. We present a case of PVNS found on surveillance imaging of a lymphoma patient. PMID- 27190772 TI - Increased low back pain prevalence in females than in males after menopause age: evidences based on synthetic literature review. AB - Female sex hormones play an important role in the etiology and pathophysiology of a variety of musculoskeletal degenerative diseases. Postmenopausal women show accelerated disc degeneration due to relative estrogen deficiency. This literature review aims to validate or falsify this hypothesis, i.e., while overall females have higher prevalence of low back pain (LBP) across all age groups, this male vs. female difference in LBP prevalence further increases after female menopause age. The literature search was performed on PubMed on January 2, 2016. The search word combination was (low back pain) AND prevalence AND [(males OR men) AND (females OR women)]. The following criteria were taken to include the papers for synthetic analysis: (I) only English primary literatures on nonspecific pain; (II) only prospective studies on general population, but not population with occupational LBP causes, of both males and female subjects studied using the same LBP criterion, ages-specific information available, and males and female subjects were age-matched; (III) studies without major quality flaws. In total 98 studies with 772,927 subjects were analyzed. According to the information in the literature, participant subjects were divided into four age groups: (I) school age children group: 6-19 years; (II) young and middle aged group: 20-50 years; (III) mixed age group: data from studies did not differentiate age groups; (IV) elderly group: >=50 years old. When individual studies were not weighted by participant number and each individual study is represented as one entry regardless of their sample size, the median LBP prevalence ratio of female vs. males was 1.310, 1.140, 1.220, and 1.270 respectively for the four age groups. When individual studies were weighted by participant number, the LBP prevalence ratio of female vs. males was 1.360, 1.127, 1.185, and 1.280 respectively for the four groups. The higher LBP prevalence in school age girls than in school age boys is likely due to psychological factors, female hormone fluctuation, and menstruation. Compared with young and middle aged subjects, a further increased LBP prevalence in females than in males was noted after menopause age. PMID- 27190777 TI - Secondary sclerosing cholangitis in a critically ill patient. AB - Critically ill patients are commonly imaged for liver dysfunction. An often fatal condition, secondary sclerosing cholangitis, is an important and likely under recognized hepatic condition in these patients. In presenting this case report, we hope to raise awareness of this condition amongst radiologists as well as other physicians caring for the critically ill. PMID- 27190778 TI - Dermatofibrosarcoma protuberans-a rare neoplasm. PMID- 27190779 TI - Ureteral endometriosis: an uncommon cause of ureteral stricture. PMID- 27190780 TI - Will the science and technology gap between China and USA becomes narrower, wider, or stay in the same in 50 years' time? PMID- 27190781 TI - Being a doctor: time for a reality check. PMID- 27190782 TI - Becoming a doctor in India: once a cherished dream, no longer cherished though. PMID- 27190783 TI - Unusual and Unique Variant Branches of Lateral Cord of Brachial Plexus and its Clinical Implications- A Cadaveric Study. AB - INTRODUCTION: Adequate knowledge on variant morphology of brachial plexus and its branches are important in clinical applications pertaining to trauma and surgical procedures of the upper extremity. AIM: Current study was aimed to report variations of the branches of the lateral cord of brachial plexus in the axilla and their possible clinical complications. MATERIALS AND METHODS: Total number of 82 upper limbs from 41 formalin embalmed cadavers was dissected. Careful observation was made to note the formation and branching pattern of lateral cord. Meticulous inspection for absence of branches, presence of additional or variant branches and presence of abnormal communications between its branches or with branches of other cords was carried out. RESULTS: In the present study, we noted varied branching pattern of lateral cord in 6 out of 82 limbs (7%). In one of the limb, the median nerve was formed by three roots; two from lateral cord and one from medial cord. Two limbs had absence of lateral pectoral nerve supplemented by medial pectoral nerves. One of which had an atypical ansa pectoralis. In 2 upper limbs, musculocutaneous nerve was absent and in both cases it was supplemented by median nerve. In one of the limb, coracobrachialis had dual nerve supply by musculocutaneous nerve and by an additional branch from the lateral cord. CONCLUSION: Variations of brachial plexus and its branches could pose both intraoperative and postoperative complications which eventually affect the normal sensory and motor functions of the upper limb. PMID- 27190784 TI - Morphometric Study of Anterior Clinoid Process and Optic Strut and the Ossification of Carotico-Clinoid Ligament with their Clinical Importance. AB - INTRODUCTION: Knowledge about the ossification of the Carotico-Clinoid Foramen (CCF), as it forms a potential site for compression of the internal carotid artery may be beneficial for neurosurgeons and radiologists. AIM: To obtain a detailed knowledge of morphometry of Anterior Clinoid Process (ACP) and Optic Strot (OS) and the type of ossification of CCF which would be necessary to increase the success of surgeries related to the cavernous sinus and internal carotid artery. MATERIALS AND METHODS: Parameters such as the length of ACP from its base to the tip, the width at its base and the distance between the tip of ACP to optic strut were measured in mm using digital calipers. SPSS version 17 was used for the statistical analysis. Paired t-test was applied to compare between right and left sides. Presence of carotico-clinoid foramen was observed and was classified as incomplete, contact form or complete. RESULTS: The average length of ACP ranged from 12 to 15mm on right side and 11 to 16mm on the left side. Paired t-test was applied to compare the means between the right and left sides. The width of ACP varied between right and left sides and this difference was statistically significant (p<0.05). Out of 12 CCF observed, the commonest type was incomplete (N=7) followed by complete (N=3) and contact form (N=2). CONCLUSION: Considering the immense anatomical surgical and radiological importance of morphology of ACP, OS and CCF, this study highlighted the detailed morphometry of these structures. The study also has explained the sexual dimorphism in their morphology. PMID- 27190785 TI - Morphometric Study of Clavicular Facet of Coracoclavicular Joint in Adult Indian Population. AB - INTRODUCTION: Anthropologists have used Coracoclavicular Joint (CCJ), a non metric anatomical variant in population, as a marker for population migration from prehistoric times to present. AIM: The aim of this osteological study was to determine the incidence and morphometry of articular facet of CCJ on conoid tubercle of clavicle in Indian population, as Indian studies are scanty and incomplete. MATERIALS AND METHODS: The study was done on 144 adult human clavicles (76 right and 68 left; 93 males and 51 females) collected from osteology museum in Department of Anatomy, Maulana Azad Medical College, New Delhi, India. The presence of articular facet on the conoid tubercle was determined and Maximum Antero-Posterior (MAPD) and maximum transverse diameter (MTD) was measured by digital vernier calliper. The incidence was compared on the basis of sex, side and with other osteological studies in the world. Statistical analysis was done using the Chi-Square test for nominal categorical data and student's t-test for normally distributed continuous variables in Microsoft Excel 2007 to assess the relationship between the examined variables. RESULTS: Articular facet on conoid tubercle was found in 8 cases (5.6%). Seven (9.2%) were present on the right side and one (1.5%) on the left side. Seven cases (7.5%) were present in males and one case (2%) was found in females. The facets were generally oval, with MAPD and MTD of 12.28 and 17.17 mm respectively. A significant side variation was present with right sided facet being more common. The left sided facet was more transversely elongated than right. In males, the facets were more elongated antero-posteriorly than in females. CONCLUSION: The Indian population showed an incidence of 5.6%, which was comparable to other ethnic groups in world population. The morphometric and side differences could be attributed to the occupational factors and range of movements associated with the CCJ. The CCJ should be borne in mind as a differential diagnosis for thoracic outlet syndrome and in general for shoulder pain. PMID- 27190786 TI - Contrast Enhanced Computed Tomographic Study on the Prevalence of Duodenal Diverticulum in Indian Population. AB - INTRODUCTION: Duodenal diverticulum (DD) is the second most common diverticulum, yet its incidence varies widely from 1-22% based on the mode of investigation. Computed Tomography (CT) of abdomen is the preferred modality to diagnose acute abdomen including those of complications of DD. Moreover, the prevalence of DD in Indian population is not yet been studied using CT. AIM: The current study aim to look for the prevalence of DD in Indian population using Contrast Enhanced Computed Tomography (CECT) abdomen. MATERIALS AND METHODS: A retrospective study was done to assess the presence of DD using the CECT abdomen of 565 patients. The number, size, location, wall thickness and the contents of the diverticulum were noted. The data obtained was analysed using SPSS version 17.0. The mean, percentage of frequency of each variable and the association of DD with pancreatitis, cholelithiasis and colonic diverticulum were also looked for. Frequencies and percentages were calculated for all categorical variables. Spearman's rho correlation was done for age, diameter and content of DD. RESULTS: The prevalence of DD in Indian population was 8.3% with the mean diameter of 17.13mm+7.26. The prevalence increased with age with no sex predilection. 89.3% were solitary and 10.64% were multiple. It was predominantly seen in the second part of duodenum (90.38%) and juxtapapillary type was the commonest. As the diameter of DD increased, fluid became its content. No significant association was observed between the presence of DD with pancreatitis, cholelithiasis or colonic diverticulum. A case of periampullary carcinoma arising from DD, a rare entity is being reported in this study. CONCLUSION: The prevalence of DD in Indian population is high compared to western population. DD has been attributed to the cases of acute abdomen and fluid alone as a content of DD with an incidence of 1.92% can be mistaken for a cystic neoplasm of pancreas. Rarely, a periampullary carcinoma can also arise from the wall of the pre-existing DD. This knowledge should be emphasised upon by the radiologist, surgeons and gastroenterologist who will be dealing with cases of acute abdomen and periampullary carcinoma. PMID- 27190787 TI - Association Between Serum B12 and Serum Homocysteine Levels in Diabetic Patients on Metformin. AB - INTRODUCTION: Type-2 Diabetes Mellitus (T2DM) and metformin both can lower serum B12 (s.B12). Raised serum Homocysteine (s.Hcy) is considered as an early marker of B12 deficiency. AIM: The study aimed to check whether homocysteine levels are more sensitive indicator of s. B12 deficiency or not among diabetics using metformin. MATERIALS AND METHODS: Mean s.B12 and s.Hcy levels of 30 cases (diabetics on metformin <5years) were compared with 30 diabetic controls not on metformin and 31 nondiabetic controls and statistically analysed by ANOVA and post-hoc tests. RESULTS: No significant differences in either s.B12 mean or s.Hcy mean were found between cases and diabetic controls. s.B12 mean did not differ significantly but s.Hcy mean was significantly higher among nondiabetics as compared to diabetic control. s. B12 level of Nondiabetic group was in borderline category while mean s. B12 levels of cases and diabetic control groups was in normal category but nearer to the lower cut off. Mean s.Hcy values in all the groups were high. Pearson correlation showed strong association between s.B12 and s.Hcy in all the groups. Additionally equation based on linear regression was derived to calculate either of the s.B12 or s.Hcy. On Receiver Operative Characteristic (ROC) curve, area under curve value was 0.842 for the value of s.Hcy. CONCLUSION: In this study neither metformin nor T2DM could be identified as a cause for s.B12 lowering and raised s.Hcy in the scenario of low normal levels of s.B12 (<300pmol/L). If B12 deficiency recognized early using s. Hcy, consequences due to B12 deficiency can be prevented or delayed among nondiabetics as well as among diabetics and metformin users. PMID- 27190788 TI - Heavy Metal Contamination in Groundwater around Industrial Estate vs Residential Areas in Coimbatore, India. AB - INTRODUCTION: Water is the vital resource, necessary for all aspects of human and ecosystem survival and health. Depending on the quality, bore water may be used for human consumption, irrigation purposes and livestock watering. The quality of bore water can vary widely depending on the quality of ground water that is its source. Pollutants are being added to the ground water system through human and natural processes. Solid waste from industrial units is being dumped near the factories, which react with percolating rainwater and reaches the ground water. The percolating water picks up a large number of heavy metals and reaches the aquifer system and contaminates the ground water. The usage of the contaminated bore water causes the diseases. Mercury, Arsenic and Cadmium are used or released by many industries. AIM: This study was conducted to investigate the pollution of bore water in the industrial region (Kurichi Industrial Cluster) of Coimbatore, in the state of Tamilnadu, India. MATERIALS AND METHODS: Four samples were taken from residential areas around Kurichi Industrial Cluster and analysed to find the concentrations of Mercury, Arsenic and Cadmium. Four more samples were taken from other residential regions far from the industrial estate and served as control. Samples were analysed using Atomic absorption spectrophotometry method. RESULTS: We found that the ground water of the areas surrounding the industrial cluster does not contain significant amount of those metals. Instead, Heavy metal contamination of ground water were observed in some residential areas of coimbatore. CONCLUSION: The regulatory measures to contain and prevent ground water contamination by industries undertaken by Tamilnadu pollution control board may have lead to absence of heavy metal contamination in Kurichi Industrial cluster, Coimbatore, India. PMID- 27190789 TI - Effect of Vitamin C Supplementation on Blood Lead Level, Oxidative Stress and Antioxidant Status of Battery Manufacturing Workers of Western Maharashtra, India. AB - INTRODUCTION: The high blood lead level induces oxidative stress and alters the antioxidant status of battery manufacturing workers. Supplementation of vitamin C is beneficial to reduce the oxidative stress and to improve the antioxidant status of these workers. AIM: The main aim of this study was to observe the changes in blood lead levels, oxidative stress i.e. serum lipid peroxide and antioxidant status parameters such as erythrocyte superoxide dismutase and catalase and serum nitrite after the vitamin C supplementation in battery manufacturing workers. MATERIALS AND METHODS: This study included 36 battery manufacturing workers from Western Maharashtra, India, having age between 20-60 years. All study group subjects were provided vitamin C tablets (500 mg/day for one month) and a blood sample of 10 ml each was drawn by puncturing the anterior cubital vein before and after vitamin C supplementation. The biochemical parameters were estimated by using the standard methods. RESULTS: Blood lead levels were not significantly altered, however, serum lipid peroxide (p<0.001, 15.56%) and serum nitrite (p<0.001, -21.37%) levels showed significant decrease and antioxidant status parameters such as erythrocyte superoxide dismutase (p<0.001, 38.02%) and catalase (p<0.001, 32.36%) revealed significant increase in battery manufacturing workers after the supplementation of vitamin C. CONCLUSION: One month vitamin C supplementation in battery manufacturing workers is not beneficial to decrease the blood lead levels. However, it is helpful to reduce the lipid peroxidation and nitrite formation and enhances the erythrocytes superoxide dismutase and catalase activity. PMID- 27190791 TI - Ischaemic Markers in Acute Hepatic Injury. AB - INTRODUCTION: Hepatic injury of varied aetiology may progress to Acute Liver Failure (ALF). Compromised microcirculation is thought to be a deciding factor of hepatic hypoxia may be involved in disease progression that needs early detection. Ischaemia markers like serum Ischaemia- modified albumin (IMA), ALT LDH ratio and ALT-LDH index have been suggested for its detection at early stage. AIM: To find out the association of Ischaemia markers like serum IMA, ALT-LDH ratio and ALT-LDH index in acute hepatic injury cases. MATERIALS AND METHODS: Forty one diagnosed acute liver injury cases of varied aetiology admitted in Department of Medicine, and Gastroenterology of SCB Medical College, Cuttack were enrolled in the study along with 30 age and sex matched healthy controls. Blood collected at time of admission and at time of discharge (1(st) day and 7(th) day) were evaluated for FPG, RFT, LFT, Serum Albumin along with serum LDH, IMA, PT-INR and platelet count. RESULT: Serum bilirubin, hepatic enzymes, IMA, PT-INR was more markedly raised in cases than controls on the 1(st) day of admission. ALT LDH ratio and index were significantly low in complicated cases. However, on responding to treatment the ALT-LDH index on 7(th) day registered a rise in comparison to the 1(st) day, while serum IMA revealed an insignificant decline showing improvement in hepatic hypoxia. ALT-LDH ratio remains more or less same on response to treatment. CONCLUSION: Serum IMA and ALT-LDH Index reveals association with disease process in Acute Hepatic Injury cases both clinically and biochemically and can be used as supportive parameters for the diagnosis of disease process. PMID- 27190790 TI - Chronic Periodontitis in Type 2 Diabetes Mellitus: Oxidative Stress as a Common Factor in Periodontal Tissue Injury. AB - INTRODUCTION: The prevalence of periodontitis is significantly higher among people with poorly controlled diabetes mellitus. Majority of tissue destruction in periodontitis is considered to be the result of an aberrant inflammatory/immune response to microbial plaque and involve prolonged release of reactive oxygen species (ROS). There is increased evidence for compromised antioxidant capacity in periodontal tissues and fluids which may be an added factor for tissue damage in periodontitis. AIM: To study the possible role of Reactive oxygen species (ROS) and antioxidant status in blood among chronic periodontitis patients with and without Type 2 Diabetes mellitus. MATERIALS AND METHODS: The study comprised of total 100 subjects among which 25 were normal healthy controls, 25 were gingivitis patients, 25 were chronic periodontitis patients (CP) and 25 were having chronic periodontitis with type 2 diabetes (CP with DM). ROS levels were determined as MDA (Malondialdehyde) and antioxidant status as plasma total antioxidant capacity (TAC), vitamin C and erythrocyte Superoxide dismutase (SOD) and catalase activity. RESULTS: There was significant increase in MDA levels in all the patient groups compared with healthy controls (p<0.05). The decrease in TAC, Vitamin C and SOD levels among CP with DM patients as compared to controls was highly significant (p<0.01). There was a positive correlation between the probing pocket depth and MDA levels among periodontitis patients with diabetes (r=0.566, p=0.003). CONCLUSION: There is increased oxidative stress in chronic periodontitis with and without type 2 diabetes indicating a common factor involvement in tissue damage. More severe tissue destruction in periodontitis is associated with excessive ROS generation which is positively correlated in type 2 diabetic subjects. PMID- 27190792 TI - Evaluation of Protein Kinase Cbeta and PPARgamma Activity in Diabetic Rats Supplemented with Momordica charantia. AB - INTRODUCTION: The present study was taken up to compare and evaluate the effect of Momordica charantia supplementation with pioglitazone on PKC-beta and PPAR gamma activity in kidneys of diabetic rats. The hypoglycaemic and lipid lowering effect of Momordica charantia were screened in laboratory animal model and its potency was compared with a Thiazolidinedione (TZD) group antidiabetic drug like pioglitazone. MATERIALS AND METHODS: Adult healthy albino rats of Wistar strain aged 3-4months, weighing between 170-250gm of either sex were divided into 4 groups; Group 1 (normal controls), Group 2 (diabetic controls), Group 3 (diabetic rats treated with pioglitazone) and Group 4 (diabetic rats treated with bitter melon juice). Type 1 Diabetes was induced in rats by intraperitoneal injection of streptozotocin at a dose of 55 mg/kg body weight, following which glucose levels were estimated by Accu chek- active glucometer on day 0, 7, 14, 21 and 28 days to assess the efficacy of Bitter Melon Juice (BMJ) and pioglitazone. After 28 days of treatment, the rats were sacrificed and blood collected from abdominal vena cava was used for estimation of triglycerides by Glycerol 3 phosphate oxidase phenol aminophenazone method and cholesterol by Cholestrol oxidase phenol aminophenazone method. PKC-beta and PPAR-gamma were estimated in the dissected kidneys by using double sandwich ELISA based kits on an automated plate reader. RESULTS: BMJ significantly reduced blood glucose levels in group 4 as compared to diabetic controls (p<0.001). Total cholesterol and triglycerides were significantly reduced in both group 3 and 4. In Group 4, there was reduction in PKC-beta levels, when compared to Group 3(p=0.004). PPAR-gamma levels were increased in both Group 3 and 4, when compared to Group 2. CONCLUSION: The results suggest that BMJ has hypoglycaemic and lipid lowering effect in diabetic animal models. BMJ increases PPAR-gamma activity and decreases PKC-beta activity in kidneys of diabetic rats, thereby preventing the complications of diabetes mellitus. Fresh BMJ mimics action of pioglitazone belonging to TZD group thus showing a potential for further research in identifying the active molecules responsible for glucose and lipid lowering action. PMID- 27190793 TI - Effect of Red Yeast Rice and Coconut, Rice Bran or Sunflower Oil Combination in Rats on Hypercholesterolemic Diet. AB - INTRODUCTION: Dietary supplements provide a novel population based health approach for treating hyperlipidemias. Red yeast rice is known to have lipid lowering effects. Combination of red yeast rice with various oils is taken by different population around the world. AIM: In this present work, we aimed to compare the effects of red yeast rice with different oil (coconut, rice bran and sunflower oil) supplementations on lipid levels and oxidative stress in rats fed on hypercholesterolemic diet. MATERIALS AND METHODS: A Randomized controlled study was conducted on 28 male Sprague Dawley rats. It included 4 arms-Control arm (hypercholesterolemic diet), Test arm A (hypercholesterolemic diet +Red yeast rice + Rice bran oil), arm B (hypercholesterolemic diet +Red yeast rice + Coconut oil) and arm C (hypercholesterolemic diet +Red yeast rice + Sunflower oil). At the end of one month, serum cholesterol, triglycerides, MDA and paraoxonase was measured. The mean values of analytes between the different groups were compared using student 't-' test. RESULTS: The rats fed with red yeast rice and rice bran oil combination showed significantly lower levels of serum cholesterol, triglycerides and MDA when compared to the controls. The serum paraoxonase levels were significantly higher in this group when compared to the controls. The rats fed with red yeast rice and coconut oil combination showed significantly lower serum cholesterol and MDA levels when compared to the controls. The mean triglyceride and paraoxonase levels did not show any statistically significant difference from the controls. The rats on red yeast rice and sunflower oil combination did not show any statistically significant difference in the lipid levels and oxidative stress parameters. CONCLUSION: The food combination which had best outcome in preventing the development of hyperlipidemia and oxidative stress in rats fed with hypercholesterolemic diet was red yeast rice and rice bran oil. Combining red yeast rice with coconut oil and sunflower oil gave suboptimal benefits. PMID- 27190794 TI - Correlation of alpha-Lipoic Acid and S. Glutathione Level with Free Radical Excess in Tobacco Consumers. AB - INTRODUCTION: Tobacco consumption is a serious health hazard and most important avoidable cause of death worldwide. Tobacco is recognized as lethal toxin, ripping off 7-11 minutes of human life with each cigarette through harmful compounds and inducing free radical synthesis and a high rate of lipid peroxidation. These free radicals are scavenged by the endogenous antioxidants viz. S. Glutathione (S.GSH) and S. alpha-Lipoic acid (S. alpha-LA), thus preventing the endothelial damage. AIM: The present study was designed with an aim to find out the lipid peroxidative stress through S. Malondialdehyde (S.MDA) and its correlation with antioxidant levels like S. Glutathione (S. GSH) and S. alpha- Lipoic acid (S. alpha- LA) among tobacco users (in both smokers and chewers). MATERIALS AND METHODS: A case control cross-sectional study was carried out in the Department of Physiology among 200 subjects; aged 18-50 years of both sexes which were chosen randomly from institutional campus and healthy volunteers. The subjects were broadly divided into two groups (A & B); group A comprised of tobacco users (n=150) with history of smoking cigarette/biddies and chewing tobacco daily, for at least one year and group B had controls (non tobacco users) (n=50). S. MDA, S.GSH and S. alpha-LA levels were estimated by standardized methods. The data was analysed by unpaired student t-test and Pearson's correlation coefficient (r) for finding the correlation between antioxidants and S.MDA in group-A and group-B. RESULTS: The present study reports the significantly higher (p<0.0001) levels of S.MDA and lower (p<0.0001) levels of S.GSH and S. alpha-LA in tobacco users as compared to nontobacco users. The observed value of S.MDA was (2.72+/-0.87, 1.39+/-0.47) nmol/ml, S. alpha-LA was (9.94+/-5.96, 14.24 +/- 4.34) MUg/ml and S.GSH was (23.24+/-7.04, 32.82+/-2.95) mg/dl respectively in group-A and group-B. A significant (p<0.01) strong negative correlation was observed between S. MDA and antioxidants (S.GSH and S. alpha-LA) with a Pearson co-efficient of r=-0.619, r= -0.625 respectively, in group A. CONCLUSION: The decreased level of S. alpha-LA and S. GSH, in our study clearly indicates potential risk of cellular damage in tobacco users due to lipid peroxidation. Hence, the present study recommends supplementation of S. alpha-LA and Vitamin C in tobacco users to prevent this damage whereas quitting this evil habit will be the best available option. PMID- 27190795 TI - Effect of Mindfulness Meditation on Perceived Stress Scores and Autonomic Function Tests of Pregnant Indian Women. AB - INTRODUCTION: Various pregnancy complications like hypertension, preeclampsia have been strongly correlated with maternal stress. One of the connecting links between pregnancy complications and maternal stress is mind-body intervention which can be part of Complementary and Alternative Medicine (CAM). Biologic measures of stress during pregnancy may get reduced by such interventions. AIM: To evaluate the effect of Mindfulness meditation on perceived stress scores and autonomic function tests of pregnant Indian women. MATERIALS AND METHODS: Pregnant Indian women of 12 weeks gestation were randomised to two treatment groups: Test group with Mindfulness meditation and control group with their usual obstetric care. The effect of Mindfulness meditation on perceived stress scores and cardiac sympathetic functions and parasympathetic functions (Heart rate variation with respiration, lying to standing ratio, standing to lying ratio and respiratory rate) were evaluated on pregnant Indian women. RESULTS: There was a significant decrease in perceived stress scores, a significant decrease of blood pressure response to cold pressor test and a significant increase in heart rate variability in the test group (p< 0.05, significant) which indicates that mindfulness meditation is a powerful modulator of the sympathetic nervous system and can thereby reduce the day-to-day perceived stress in pregnant women. CONCLUSION: The results of this study suggest that mindfulness meditation improves parasympathetic functions in pregnant women and is a powerful modulator of the sympathetic nervous system during pregnancy. PMID- 27190796 TI - Impact of Seasonal Variant Temperatures and Laboratory Room Ambient Temperature on Mortality of Rats with Ischemic Brain Injury. AB - INTRODUCTION: A popular rat model for hypoperfusion ischemic brain injury is bilateral common carotid artery occlusion (BCCAO). BCCAO surgery when performed in varying geographical locations and during different seasons of the year is reported to have variable mortality rates. Studies have also documented the diminishing influence of Ketamine-Xylazine (KT-XY) on thermoregulatory functions in rodents. AIM: To explore the impact of seasonal variant temperatures and laboratory room ambient temperatures on mortality of rats following BCCAO surgery. MATERIALS AND METHODS: The study has two parts: 1 The first part is an analysis of a three year retrospective data to explore the association between the geographical season (hot summer and cold winter) induced laboratory room ambient temperature variations and the mortality rate in KT-XY anaesthetized BCCAO rats. 2. The second part investigated the effect of conditioned laboratory room ambient temperature (CAT) (23-25(0)C) in KT-XY anaesthetized BCCAO group of rats. Rats were divided into 4 groups(n =8/group) as-Normal control, BCCAO and Sham BCCAO where they were all exposed to unconditioned ambient temperature (UCAT) during their surgery and postoperative care. And finally fourth group rats exposed to CAT during the BCCAO surgery and postoperative care. RESULTS: Pearson's chi-square test indicates a significantly high association (p<0.006) between post-BCCAO mortality and hot season of the year. CAT during the hot season reduced the mortality rate (24% less) in post- BCCAO rats compared to the rats of UCAT. CONCLUSION: Despite seasonal variations in temperature, conditioning the laboratory room ambient temperatures to 23-25(0)C, induces hypothermia in KT-XY anaesthetized ischemic brain injured rodents and improves their survival rate. PMID- 27190797 TI - Implication of Renal Aquaporin-3 in Fructose-Induced Metabolic Syndrome and Melatonin Protection. AB - INTRODUCTION: Metabolic Syndrome (MetS) can be induced by ingestion of large amounts of fructose as a consequence of oxidative stress and dyslipidemia. AIM: We investigated the possible protective effects of melatonin administration on MetS induced in fructose-fed rats with special focus on the role of renal aquaporin-3 (AQP-3). MATERIALS AND METHODS: Thirty rats were randomly divided into three groups; control, fructose, and fructose plus melatonin. MetS was induced by fructose rich diet and melatonin was injected at a dose of 5 mg/kg dissolved in 1% ethanol in normal saline. After the end of the 6-week experimental period, body weight and fat accretion were assessed. Invasive blood pressure and vascular reactivity were evaluated. Serum lipid profile, glucose, insulin levels, insulin resistance, malondialdehyde (MDA) and uric acid were measured, also underwent renal AQP-3 immunohistochemistry. RESULTS: Fructose consumption significantly increased fat accretion, systolic blood pressure, serum lipids, insulin levels and insulin resistance, confirming successful establishment of the MetS model. Also serum MDA, uric acid and renal AQP-3 expression increased compared to the control group. Melatonin supplementation significantly decreased the previously measured parameters compared to fructose group. CONCLUSION: Increased AQP-3 expression may be implicated in fructose induced MetS. Melatonin protective effect against metabolic consensus and vascular affection may be linked to its antioxidant and lipid lowering effect with reduced renal AQP-3 expression. PMID- 27190798 TI - Evaluation of NS1 Antigen Detection for Early Diagnosis of Dengue in a Tertiary Hospital in Southern India. AB - INTRODUCTION: Dengue is a mosquito-borne disease affecting mainly tropical and subtropical regions of the world. The early diagnosis of dengue is required for identifying an epidemic and also for implementing effective vector control measures. AIM: To evaluate NS1 antigen assay as an alternative to RT-PCR for the early diagnosis of Dengue. MATERIALS AND METHODS: A comparative study was conducted to evaluate NS1 antigen assay in clinically suspected dengue cases admitted to JIPMER hospital from January to November 2011. Serum samples were tested for NS1 antigen, IgM and IgG antibodies by ELISA and RT-PCR. RESULTS: Out of total 112 clinically suspected dengue, 94 were laboratory-confirmed dengue cases (positive by one or more of the following tests - IgM ELISA, NS1 antigen ELISA and RT-PCR). NS1 was detectable from day 1 to day 12 of fever. The positive detection rate of NS1 antigen ELISA, RT-PCR and IgM ELISA were 80.9%, 68.1% and 47.9% respectively. NS1 antigen ELISA was evaluated using RT-PCR as the reference standard and showed a sensitivity of 96.8%, specificity of 53.3%, positive predictive value of 81.6% and negative predictive value of 88.9% with a likelihood ratio of 2.1 by Fisher's-exact test. The combination of NS1 and IgM had the highest sensitivity of 97.8%. DEN-3 was the serotype identified by RT-PCR for 24 randomly selected samples. NS1 antigen detection had the highest sensitivity in the early stages while IgM detection was more sensitive in the later half of the illness. CONCLUSION: Both NS1 and RT-PCR are useful for early dengue diagnosis, although in terms of cost, ease of performance and rapidity, NS1 is superior to RT-PCR. NS1 in combination with IgM assay offers the most sensitive and cost-effective diagnostic modality for dengue. PMID- 27190799 TI - Application of Radial Basis Function Network Tool for Correlation of CD4+ Count with Plasma Viral Load in HIV-Seropositive Individuals. AB - INTRODUCTION: Human Immunodeficiency Virus (HIV) infects and cripples the immune system of the body. The two important marker CD4+T cells and Plasma viral load are crucial not only in understanding the disease progression but also in starting the antiretroviral therapy. A lot of research is going on in understanding the dynamic nature of HIV. AIM: To find the correlation between CD4+ count and Plasma Viral Load (PVL) measured by two different technologies; with the help of correlation technique in conjunction with the three dimensional HIV model with a purpose of establishing a mathematical model between the CD4+ cells and PVL using a sinusoidal function as well as Radial Basis Function (RBF) neural network. MATERIALS AND METHODS: Plasma Viral Load were determined by two different methods viz Exavir Cavidi(TM) and Abbott Real time HIV-1 assay and then they were correlated with the CD4+ count with the help of computational intelligence in predicting viral load. RESULTS: It was found that there exists a positive correlation between the CD4+ cells and viral loads. A correlation value of 0.4082 and 0.3652 was observed between CD4+ cells and viral measured using Exavir Cavidi(TM) and Abbott Real time HIV-1 assay respectively. CONCLUSION: The existence of positive correlation had helped us to understand the nature and dynamic of the existence of HIV and how the CD4 + and PVL act. PMID- 27190800 TI - ESBL and MBL in Cefepime Resistant Pseudomonas aeruginosa: An Update from a Rural Area in Northern India. AB - INTRODUCTION: Cefepime, a fourth generation cephalosporin, is widely used for the empirical treatment of serious infections in critically ill hospitalized patients. Pseudomonas aeruginosa (P. aeruginosa), one of the commonest bacteria causing nosocomial infections has a propensity to develop antibiotic resistance quite promptly. AIM: We undertook this study to assess the efficacy of cefepime against current clinical isolates of P. aeruginosa and to study existence of different beta-lactamase enzymes among cefepime resistant P. aeruginosa isolates. MATERIALS AND METHODS: Total of 618 isolates of P. aeruginosa recovered consecutively from various clinical samples of a tertiary care hospital were analysed. Their Antimicrobial sensitivity profile against piperacilin (100MUg), piperacillin/tazobactam (100MUg/10MUg), ceftazidime (30MUg), cefoperazone (75MUg), cefepime (30MUg), ciprofloxacin (5MUg), gentamycin (10MUg), amikacin (30MUg) and imipenem (10MUg) (Himedia) was tested by Kirby-Bauer disc diffusion method (Clinical and Laboratory Standards Institute guidelines). We further looked for ESBL, MBL and ESBL + MBL co producers among the cefepime resistant isolates by two different methods (combined double disc synergy test, imipenem EDTA combined disc test and vitek2). RESULTS: Among 618 consecutive clinical isolates of P. aeruginosa, we observed resistance to cefepime in 457 (74%) isolates. We observed resistance to ciprofloxacin (n=506, 82%) in maximum number of isolates followed by that to Gentamycin (n=475, 77%), amikacin (n=366, 60%), and cefoperazone (n=350, 56.6%). Among all our cefepime resistant P. aeruginosa isolates only 27(6%) were ESBL producers, 18(4%) MBL producers and 2(0.4%) were ESBL+ MBL co-producers. All the ESBL and MBL isolates were also tested by VITEK 2 advanced expert system (bioMirieux Vitek Systems Inc, Hazelwood, MO, France) which revealed a 100% concordance with the phenotypic method tested. CONCLUSION: This paper highlights the need to reconsider prescribing empirical antibiotics for Pseudomonas infections in this region and formulate a strong antibiotic policy to curb the menace of spread of multidrug resistant strains. PMID- 27190801 TI - Comparison of Antigen Detection and Nested PCR in CSF Samples of HIV Positive and Negative Patients with Suspected Cryptococcal Meningitis in a Tertiary Care Hospital. AB - INTRODUCTION: The cases of cryptococcal meningitis and other forms of cryptococcosis have increased in recent time and the present scenario of the condition with significant morbidity and mortality is actually posing a serious threat to the community, so an early and prompt diagnosis is necessary to prevent serious complications and thus improving the overall disease outcome. AIM: Comparison of diagnostic efficacy of nested Polymerase Chain Reaction (PCR) with Latex Agglutination Test (LAT) in the Cerebro Spinal Fluid (CSF) samples of the cases of meningitis in HIV positive and negative cases. MATERIALS AND METHODS: We have compared the diagnostic efficacy of Latex Agglutination Test (LAT) with nested Polymerase Chain Reaction (PCR) in 200 Cerebrospinal Fluid (CSF) samples, including 14 HIV positive also, in the cases of suspected cryptococcal meningitis. Nested PCR was done in all cases reporting positive by LAT and results were then compared with that of India ink and culture on Sabouraud Dextrose Agar (SDA), and the isolates were further identified by urease, nitrate and sugar assimilation tests. RESULTS: Of the 200 cases, including 14 HIV positive, LAT was positive in 46 cases while 154 were negative. Out of these 46 LAT positive cases, nested PCR was positive in 40 cases only, while culture and India ink was positive in 38 and 33 cases respectively. Majority of the cases, 30 (65.2%) were between age group 21-50 years, while 2 (4.3%) in 0-20, and 14 (30.4%) in 51-80 years age group. CONCLUSION: Although negative staining like India ink and nigrosin are most widely used techniques, but these suffer with subjective error. Rapid method like LAT is available but it always has the scope of false positive and negative results. In such cases nested PCR can help in establishing final diagnosis. PMID- 27190803 TI - Comparison Between Biofilm Production, Phospholipase and Haemolytic Activity of Different Species of Candida Isolated from Dental Caries Lesions in Children. AB - INTRODUCTION: C.albicans is the most commonly isolated fungal pathogen in the oral cavity, but isolation of non-albicans Candida is increasing in recent years. We wish to demonstrate the virulence factors of Candida spp. isolated from the dental caries lesion of the children as presence of virulence factors determines the pathogenic potential of any microorganism. AIM: To compare biofilm production, phospholipase and haemolytic activity of C.albicans with that of non albicans species of Candida isolated from dental caries lesions of children to evaluate the role of non- albicans species of Candida in formation of dental caries. MATERIALS AND METHODS: Oral swabs were collected from caries lesion of 100 school children of age 5-10 years with dental caries. Candida isolates were tested for biofilm production, phospholipase and haemolytic activity. Statistical analysis was done by Chi-Square test and Mann-Whitney U test wherever applicable using SPSS version 11.5. RESULTS: Out of the 100 children with dental caries 37 were positive for Candida by smear or culture and 31 by culture. C.albicans was the most prevalent isolate followed by C.krusei, C.tropicalis and C.albicans. Out of 21 C.albicans isolates, 10 (47.6%) showed phospholipase activity and 18 (85.71%) produced biofilm. Of the 10 non-albicans strains, 5 (50%) showed phospholipase activity and 6 (60%) produced biofilm. All isolates of Candida produced haemolysin (100%). CONCLUSION: There was no statistically relevant difference between the virulence factor production by C.albicans and non-albicans species of Candida. In other words, our study shows that both C.albicans and non albicans species of Candida isolated from caries lesions of the children, produce these virulence factors. So we can say that non-albicans species of Candida also are involved in caries formation. PMID- 27190802 TI - Diabetes Mellitus has no Significant Influence on the Prevalence of Antenatal Asymptomatic Bacteriuria. AB - INTRODUCTION: Diabetes is a known risk factor for asymptomatic bacteriuria (ASB). However, the influence of diabetes on antenatal ASB was previously not addressed. AIM: The prevalence of ASB, effect of risk factors and type of isolates and susceptibility patterns were studied in diabetic pregnancy. MATERIALS AND METHODS: A total of 311 pregnant women were recruited for this study of which 103 were diabetic and 208 non-diabetic. A clean catch midstream urine samples were collected and cultured. The isolates were identified and antibiotic sensitivity was studied. The data was analysed by Chi-square test. RESULTS: The prevalence of ASB in diabetic pregnancy was 38.83% (40/10(3); 95% CI: 23.73 - 53.94) and in non diabetic pregnancy was 37.98% (79/208; CI: 27.28- 48.68). The odds ratio was not significant 1.0225 (95% CU: 0.65 - 1.599; p=0.922) and associated factors such as age and gestational period had no effect. The major isolates were Escherichia coli (25.0%), Staphylococcus aureus (22.5%), Coagulase negative staphylococci (CONS) (20.00%), and Klebsiella pneumonia (20.00%) in diabetic pregnancy and CONS (31.7%), E.coli (24.0%) and K.pneumonia (16.5%) in non-diabetic pregnancy. The isolates of diabetic pregnancy showed highest susceptibility to nitrofurantoin (56.4%), gentamicin (38.5%) and cotrimoxazole (38.5%) whereas that of non diabetic pregnancy to gentamicin (43.0%), azithromycin (32.9%) and norfloxacin (30.4). There was no significant (p<0.05) difference in the type and susceptibly of the isolates between diabetic and non-diabetic pregnancy. CONCLUSION: Diabetes has no significant influence on the prevalence of ASB in diabetic pregnancy both in terms of isolates and antibiotic susceptibility pattern. PMID- 27190805 TI - Umbilical Sepsis Caused by Multidrug Resistant Strain of Kocuria kristinae in a New Born: A Case Report. AB - Kocuria species were placed previously under the genus Micrococcus, are skin and oropharynx commensals in mammals, including man. A rare bacteria, Kocuria kristinae isolated from a new born with umbilical sepsis. Identification and antibiotic susceptibility was done by Vitek 2 compact system (Biomerieux). The isolate was sensitive to higher antibiotics like vancomycin, teicoplanin and linezolid. As this new pathogen resembles coagulase negative staphylococcus, it should not be misidentified. PMID- 27190804 TI - Brucellosis in Occupationally Exposed Groups. AB - INTRODUCTION: In India, high incidence of human brucellosis may be expected, as the conditions conducive for human brucellosis exist. Limited studies have been undertaken on human brucellosis especially in occupationally-exposed groups. AIM: To estimate prevalence of anti-brucellar antibodies, evaluate the clinical manifestations, risk factors and Knowledge, Attitude and Practices (KAP) levels about brucellosis among occupationally exposed groups. MATERIALS AND METHODS: Blood samples were collected from 2337 occupationally exposed individuals. The serum samples were screened for the presence of anti-brucellar antibodies by Rose Bengal Plate Test (RBPT), Serum Agglutination Test (SAT) and 2-Mercaptoethanol test (2-ME). Clinical manifestations, risk factors and KAP levels were evaluated by personal interview using a structured questionnaire. RESULTS: Seroprevalence of brucellosis by RBPT, SAT and 2-ME test was 9.46%, 4.45% and 3.64 % respectively. Clinical symptoms resembling brucellosis were seen in 91 subjects. The major risk factors were animal exposure in veterinarians and abattoirs, both animal exposure and raw milk ingestion in farmers and shepherds, exposure to raw milk and its ingestion in dairy workers and exposure to Brucella culture in laboratory workers. Except laboratory workers, few veterinarians and dairy workers none had heard about brucellosis. KAP levels regarding brucellosis were too poor in all the groups except laboratory workers. CONCLUSION: Brucellosis most of the times was missed or misdiagnosed. Regular screenings for brucellosis and awareness programmes to increase KAP levels are necessary to control brucellosis in occupationally exposed groups. PMID- 27190806 TI - Candidal Vertebral Osteomyelitis in the Midst of Renal Disorders. AB - Vertebral osteomyelitis also known as discitis/pyogenic spondylitis refers to inflammation of the vertebral disc space. It is commonly seen in men and adults more than 50 years of age. Fungal osteomyelitis is a rare scenario compared to its bacterial counterpart. Spinal epidural abscess is a dangerous complication associated with vertebral osteomyelitis. Here, we report two cases of vertebral osteomyelitis caused by Candida tropicalis in patients with renal disorders (stage 5 chronic kidney disease and nephropathy). One of the case discussed here presented with spinal epidural abscess. Both the patients were started on antifungal therapy. One patient responded to treatment while the other was lost to follow up. PMID- 27190807 TI - Paragonimiasis in a Child from Assam, India. AB - Paragonimiasis or lung fluke infection is one of the neglected tropical parasitic disease which is found worldwide. Several endemic foci have been discovered in the Northeast India. Pulmonary paragonimiasis presenting with haemoptysis is generally mistaken for pulmonary tuberculosis. Herein, we present a case of pulmonary paragonimiasis, which initially presented with haemoptysis and remained undiagnosed for two years. The patient was treated with Praziquantel 25mg/kg thrice daily for two days along with the supportive care. Subsequently, on follow up after three months the patient had improved with no fever and cough. PMID- 27190808 TI - Antibiotic Adjuvant Therapy for Multi-Drug Resistant Carbapenemases Producing Klebsiella pneumoniae Associated Sepsis: A Case Study. AB - Rising resistance and spread of K. pneumoniae strains, create great concerns in treating sepsis patients due to high incidence of mortality and morbidity. The current study is a case of a 20-year-old male with sepsis and bilateral lung lesions infected with Multi-Drug Resistant (MDR) carbapenemase producing K. pneumoniae (KPC) showing resistance to carbapenem and polymyxin. Based on sensitivity report, patient was put on antibiotic adjuvant: Elores (ceftriaxone, sulbactam, disodium edetate) along with fluconazole for 10 days. Elores was instituted with remarkable recovery and patient was discharged. PMID- 27190809 TI - Profile of Kidney Histopathology in Cases of Burns - Particular Emphasis on Acridine Orange Fluorescence Study and to Explore its Forensic Utility. AB - INTRODUCTION: The major cause of death in the burn patients includes multiple organ failure and infection but, sometimes the exact cause of death in many fatally burned patients is difficult to detect. Many times in medico-legal post mortem examinations in cases of burns, histopathological examination of organs is requested. AIM: The aim was to study various histopathological changes in kidneys in the post-mortem cases of burns, by using routine Haematoxylin and Eosin stain (H&E stain), special Periodic and Schiff's Stain (PAS) stain, to study the role of acridine orange fluorescence study, to explore the forensic utility of this microscopic study and to find out the relationship between duration of survival and histopathological changes observed. MATERIALS AND METHODS: An experimental longitudinal prospective study from October 2010 to September 2012. Total 32 cases of death due to burns were autopsied at mortuary, the Department of Forensic Medicine and Toxicology in our hospital. Bilateral kidneys were removed and preserved in 10% formalin solution. These were forwarded to Department of Pathology for histopathological examination. Routine microscopic examination by H&E stain as well as PAS stain and fluorescence study by acridine orange stain were done in all cases. RESULTS: It was observed that in 21 (65.63%) cases gross findings in kidneys were normal, in 06 (18.75%) were grossly pale and in 05 (15.62%) heavy & congested. Sections taken from kidneys and studied by H&E stain showed overlapping histopathological changes in all cases. In 26 (81.25%) cases, changes of Acute Tubular Necrosis (ATN) while in remaining 06 (18.75%), changes of cloudy swelling were observed. The sections stained by acridine orange and observed under fluorescent microscope were lightly positive in 15 (46.88%), brightly positive in 08 (25.00%) whereas, negative in 09 (28.12%). CONCLUSION: Microscopy by various methods helps in getting specific lesions in kidney due to burns. However, it does not add any new tool to resolve any forensic issues of burns. Therefore, microscopy (including florescent), if done would be redundant. PMID- 27190810 TI - The Er/Ki-67 Proportion in Breast Tumours - An Immunohistochemical Study. AB - INTRODUCTION: Breast tumours are classified as benign, proliferative and invasive tumours. Estrogen hormone influences the proliferative activity and progression of the tumour. Estrogen Receptor (ER) status and proliferative index (Ki 67) are important histopathological factors in the development and prognosis of these tumours. AIM: The present study was aimed to evaluate the variations in ER and Ki 67 expression in three broad categories of breast lesions namely benign breast disease, proliferative breast disease and malignant breast disease. MATERIALS AND METHODS: ER% and Ki-67% was evaluated on the histopathological tissues of 15 patients each of benign, proliferative and invasive breast tumours. The ER+/ Ki 67+/- ratio was calculated and the variation of expression between the three categories was analyzed using student's t-test. Pearson's coefficient of correlation was used to correlate ER and Ki-67 positivity within each category. RESULTS: The mean ER+/Ki-67+ in benign, proliferative and invasive tumours was 0.81, 0.87 and 1.42 respectively. A statistically significant difference in ER+/Ki-67+ proportions was observed between proliferative breast disease category and malignant breast disease category and also between benign breast disease category and malignant breast disease category (p<0.05). However, no significant difference was observed in benign breast disease category and proliferative breast disease category (p>0.05). A significant correlation was observed in proliferative breast disease and malignant breast disease categories. However, no significant correlation was observed in benign breast disease category. CONCLUSION: ER+/Ki-67+ ratio is an important determinant of the invasive breast cancer and can be used to differentiate invasive cancers from benign and proliferative breast tumours. PMID- 27190811 TI - Clinico-Histopathological Spectrum of Infectious Granulomatous Dermatoses in Western India- A Representative Study from Mumbai. AB - INTRODUCTION: Infectious Granulomatous Dermatoses (IGDS) have various aetiological factors with a considerable overlap in the histopathological and clinical features, thus posing a diagnostic dilemma for dermatologists and pathologists. AIM: We aimed at determining the histopathological profile of IGDS correlating it with clinical features with an attempt to find the aetiology. MATERIALS AND METHODS: In a cross-sectional study conducted in a tertiary referral center of Mumbai over two years, out of 1872 skin biopsies received, 239 histopathologically diagnosed cases of IGDS were studied for histopathological features of granuloma. A clinico-histopathological correlation was attempted. Chi square test was used for comparison of proportions of different groups. RESULTS: Leprosy (211 cases) and tuberculosis (28 cases) were the commonest histopathologically diagnosed IGDS. Leprosy spectrum included BT (30.33% cases), followed by TT (21.32%), BL and LL and 21.79% cases of lepra reactions. Skin TB biopsies on histopathology showed lupus vulgaris (53.85% cases), scrofuloderma (15.38%), TBVC and papulonecrotic tuberculid (11.54% each). In leprosy maximum clinico-pathological agreement was seen at tuberculoid pole (TT 72.7% and BT 56.6%). Among tuberculosis cases, scrofuloderma (100%) and lupus vulgaris (53.8%) showed maximum agreement. CONCLUSION: Leprosy and skin TB are the commonest IGDS in Mumbai region though difficult to diagnose and subcategorize with certainty during initial stages. Histopathology plays the important role to elucidate the dilemma. This being a single center study, more such studies with a larger sample size are recommended to get more elaborate data and regional prevalence of these IGDS for a better overall approach to prevention, treatment and control. PMID- 27190813 TI - Massive Broad Ligament Cellular Leiomyoma with Cystic Change: A Diagnostic Dilemma. AB - Leiomyomas are known to arise from uterus, but rarely from broad ligament. Further, cellular leiomyoma of broad ligament is the least common variant reported in literature. The diagnostic dilemma arises when leiomyomas undergo degenerative changes. This poses both clinical and radiological difficulty in differentiating with an ovarian tumour. We present an unusual case of a huge broad ligament mass measuring 29x19x09cm, mimicking an ovarian tumour both clinically and radiologically. Histopathology revealed cellular leiomyoma of broad ligament with cystic and myxoid degeneration hereby being the second case reported in literature. This case is being presented not only because of the rare incidence but also due to its diagnostic confusion with ovarian malignancy on clinical evaluation and radiological findings. PMID- 27190812 TI - Collapsing Glomerulopathy: A Single Centre Clinicopathologic Study of Seven Years. AB - INTRODUCTION: Collapsing Glomerulopathy (CG) is recognized as distinct pattern of proliferative parenchymal injury with poor response to empirical therapy. AIM: A single center retrospective study was carried out to find out clinicopathological features of idiopathic CG. MATERIALS AND METHODS: A total of 3335 native renal biopsies were analyzed retrospectively which were performed from 2008 to 2014 with emphasis on clinicopathological correlation and histopathological presentation. RESULTS: Idiopathic CG constituted 0.75% incidence (25 out of 3335 biopsies) of all biopsies, adults constituting major study part with 88%. The duration of the symptoms at the time of biopsy was 34.12+/-26.09 days and 35+/ 22.91 days respectively in adults and children. Hypertension was noted in 9(40.9%) and oliguria in 8(36.4%) in adults. Urinalysis revealed microscopic haematuria 12(54.5%) in adults. Nephrotic range proteinuria was reported in 10 (45.5%) adult patients. Glomerular collapse with hyperplasia/ hypertrophy of podocytes was seen in 4.54+/-3.11 glomeruli. Tubular microcystic dilation was seen in 16(64%) patients. Tubular atrophy involving mild (t1) in 15(60%), moderate (t2) in 4(16%) and severe (t3) in 6(24%) patients. Interstitial fibrosis was mild (i1) in 17(68%), moderate (i2) in 2(8%) and severe (i3) in 6(24%) patients. CONCLUSION: Idiopathic CG is a morphological pattern of grave podocyte injury with poor prognosis. However, there are chances of remission/ recovery if the tubular atrophy and interstitial fibrosis are of grades <= t1 i1. PMID- 27190814 TI - Giant Placental Chorangioma: A Rare Case Report. AB - Chorangioma is a nontrophoblastic benign vascular tumour of the placenta, arising from the primitive chorionic mesenchyme. The clinical significance is related to the size of the tumours. Small chorangiomas, with a frequency of about 1%, are often asymptomatic. On the contrary, giant chorangiomas, greater than 5 cm in diameter, are rare tumours, with prevalence ranging from 1:9,000 to 1:50,000, and often associated with a variety of pregnancy complications and a poor perinatal outcome. We report a case of 26-year-old female who presented to us at 36 weeks of gestation with pain in the lower abdomen. Ultrasonograpy revealed polyhydramnios and a vascular tumour on the surface of placenta. Proper conservative antenatal management was done and a full term healthy baby was delievered. Histopathological examination of the extracted mass confirmed the diagnosis of chorangioma. The novelty of this report lies in the presence of large nontrophoblastic vascular placental tumour and the absence of any fetal complications. We emphasise the need of regular and timely antenatal management to diagnose and treat the complications of chorangioma at an early stage. PMID- 27190815 TI - Inflammatory Myofibroblastic Tumour of Thyroid with its Prominent Spindle Cell Pattern: A Rare Case Report. AB - Inflammatory myofibroblastic tumour of thyroid is very rare. Only 18 cases reported so far. Here we report a case of Inflammatory myofibroblastic tumour with its prominent spindle cell (fibrohistiocytic) pattern in a 61-year-old male patient. The dominant histological pattern in our case was myofibroblastic in contrast to prominent lymphoplasmocytic pattern in other previously reported cases. The tumour was strongly positive for vimentin, Anaplastic lymphoma kinase and showed focal positivity for Smooth Muscle Actin. The patient was treated with total thyroidectomy and he is comfortable after surgery. PMID- 27190816 TI - Microfilariae, a Common Parasite in an Unusual Site: A Case Report with Literature Review. AB - Filariasis is common in tropical countries. Wuchereria bancrofti is the most common parasite which causes lymphatic filariasis in India. This paper reports the finding of microfilariae in cervicovaginal smear of a 61-year-old post menopausal woman with a brief review of literature. There are limited numbers of reports describing the presence of microfilariae in the cervicovaginal smears and even rarely as an incidental finding. It is very important to keep in mind and screen for microfilariae in the non-endemic areas also. PMID- 27190817 TI - Fine Needle Aspiration Cytology Diagnosis of an Urachal Adenocarcinoma. AB - Urachal Carcinoma (UC) is a rare malignancy of urinary bladder. It is usually found in adults in advanced stages because the tumour often grows outside the bladder without producing clinical symptoms. Most of the cases are mucinous, intestinal or signet ring cell adenocarcinoma and the diagnosis is usually made on biopsy. Radiographic images of this tumour may show characteristic features with a midline solid or cystic mass in the anterior wall of bladder associated with small calcification, which is considered as a pathognomonic sign for the diagnosis of UC. We report a case of UC in an adult, whose radiographic images suggested an urachal tumour and Fine Needle Aspiration (FNA) cytology revealed an adenocarcinoma. Laparoscopic partial cystectomy with umbilectomy and pelvic node dissection was done without further histopathological confirmation. Surgical intervention of UC on the basis of FNA diagnosis has not been reported in the literature. PMID- 27190818 TI - A Rare Case of Haemoperitoneum in Pregnancy. AB - Haemoperitoneum in pregnancy is a rare, but potentially fatal condition. Primary hepatocellular carcinoma (HCC) in pregnancy is also very uncommon. Primary hepatocellular carcinoma occuring in a pregnant lady and presenting with massive haemoperitoneum is, to the best of our knowledge, the first case to be reported in world literature. Here we present a case of 32-year-old female who had no typical risk factors for HCC; was in nineteenth week of gestation presented with abdominal pain. Following a spontaneous expulsion of a dead and macerated foetus, she developed massive haemoperitoneum due to rupture of a liver mass. This caused a great diagnostic challenge for us to differentiate between the benign Hepatocellular Adenoma (HA) and well differentiated HCC because of the age and typical clinical presentation favouring HA and the histopathological features favouring more for HCC. Diagnosis of HCC was confirmed based on the immunohistochemical findings. The differential diagnosis between HA and well differentiated HCC is very difficult and sometimes impossible especially when it occurs in young females and in pregnancy. PMID- 27190819 TI - A Unique Presentation of Primary Intestinal MALT Lymphoma as Multiple Lymphomatous Polyposis. AB - Multiple lymphomatous polyposis is considered to be a rare condition, with most of the cases being extranodal counterpart of mantle cell lymphomas. We report a rare case of multiple lymphomatous polyposis of the gastrointestinal tract in which the patient presented with abdominal pain and bloody diarrhea. Computer tomography of the abdomen showed circumferential wall thickening with intramural mass involving caecum & ascending colon with enlarged pericolonic lymph nodes. The patient underwent right hemicolectomy. Immunohistologic findings were characteristic of MALT lymphoma. Microscopic examination of polypoidal masses and mesenteric lymph nodes revealed infiltration by pleomorphic, atypical lymphoid cells which were CD20 positive and negative for CD3, CD10, Cyclin D1. Lymphoepithelial lesions were also noted. Careful endoscopic evaluation and histopathological review along with an immunohistochemical panel is extremely useful for accurately diagnosing such cases and avoiding unnecessary surgery and inappropriate therapy. PMID- 27190820 TI - Blue Cell Tumour at Unusual Site: Retropritoneal Ewings Sarcoma. AB - Ewing's sarcoma is a highly malignant tumour of osseous or non-osseous origin, tremed as extra-skeletal Ewings sarcoma if arising from soft tissue. It is rare occurrence tumor most commonly occurring in paravertebral area, chest wall, head & neck and retroperitoneum. Reporting an interesting case of retroperitoneal Ewing's sarcoma in 39 years old female. Patient had complains of abdominal discomfort & vague pain since 2 months, following weakness in lower limb and loss of weight. On detail history and examination she was further referred to detail pathological and radiological investigations. Haematological profile, renal function test and liver function test were in normal limits. USG abdomen was normal, MRI showed a mass in pelvis retroperitoneum measuring 10x10cms, bilateral ovaries and tubes were normal. Because of retroperitoneal nature of tumor and suspicion of uterine sarcoma, laparotomy was performed. The large retroperitoneal mass adherent to posterior of uterus was excised and send for histopathological diagnosis. On gross and microscopy examination the diagnosis of blue cell tumor with PAS positivity, possibility of extraskeletal Ewing's sarcoma/primitive neuro ectodermal tumor was made which was further confirmed by immunohistochemistry, positive for S100, Vementin and CD99 and negative for desmin and CK. Confirmed diagnosis help in accurate management and improves survival rate. PMID- 27190821 TI - Parathyroid Adenoma Associated with Granulomatous Inflammation: A Curious Cause of Hypercalcaemia. AB - Primary Hyperparathyroidism (PHPT) due to solitary parathyroid adenoma followed by parathyroid hyperplasia and carcinoma are the most frequent cause of hypercalcaemia. The most common granulomatous disorders causing hypercalcaemia are sarcoidosis and tuberculosis. We have reported a case where unexplained granulomas were seen along with parathyroid adenoma. PMID- 27190822 TI - Leukaemic Transformation of Multiple Myeloma in Post Chemotherapy Remission Phase. AB - Plasma cell leukaemia is diagnosed when plasma cells are >20% in the peripheral blood. Plasma cell leukaemia may be present at the time of diagnosis (primary plasma cell leukaemia) or may evolve from multiple myeloma (secondary plasma cell leukaemia). We report case of a 62-year-old male who was diagnosed with multiple myeloma. He was treated with combination of prednisolone, melphalan and thalidomide. After 6 years he had Worsening of symptoms and also developed a scalp swelling. The swelling was diagnosed as plasmacytoma on fine needle aspiration cytology and confirmed on histopathology. Complete haemogram showed Haemoglobin - 8g/dl, Total Leucocyte Count - 4300/MUl, Differential leucocyte count - Neutrophil-40%, Lymphocyte-28%, Eosinophil-01%, Monocyte-10%, Atypical cells-21%, Platelet count- 1.5 lacs/MUl. Peripheral blood showed rouleaux formation and plasma cells. Serum protein electrophoresis revealed an M spike (3.26 g/dl). So, patient was diagnosed as secondary plasma cell leukaemia. Weekly bortezomib and dexamethasone combination chemotherapy was given to the patient. Patient is on monthly follow up. Here we present a detailed case history of this patient. PMID- 27190823 TI - Lipoleiomyoma of Cervix. PMID- 27190824 TI - A Study of Prescription Pattern of Neutraceuticals, Knowledge of the Patients and Cost in a Tertiary Care Hospital. AB - INTRODUCTION: Neutraceuticals are increasingly becoming a part of diet in a health-conscious society. People have changed their outlook towards neutraceuticals because of varying lifestyle diseases and they see the need to improve their physical and mental health. AIM: To study the prescription pattern by doctors, knowledge of patients, cost for patients and patient satisfaction regarding neutraceuticals. MATERIALS AND METHODS: Total of 120 patients were included in the study after obtaining written informed consent. The patients were interviewed and the prescriptions and bills were scrutinized. The data was gathered based on a structured pretested questionnaire comprising of socio demographic variables, their knowledge of neutraceuticals and history of regular usage, reason for their use, total cost for a month on neutraceuticals alone. The data was analysed using tests of proportions and percentages. RESULTS: Vitamins were prescribed maximum in Internal Medicine (51%), Orthopaedics (43%) and Surgery (37%). Minerals were prescribed maximum in Obstetrics and Gynaecology (30%). 66% of the patients were aware about neutraceuticals. The awareness was maximum in medicine department (70%) and least in surgery department (63.3%). The study showed that the average amount that the patients spent was Rs 357.45 per month on neutraceuticals alone, maximum was Rs 557 in orthopaedics and minimum was Rs 219 in medicine respectively. A 61.6% of the patients expressed their satisfaction after taking the neutraceuticals. However, 12.45% of the patients were dissatisfied even after taking the neutraceuticals. CONCLUSION: Neutraceuticals are being increasingly perceived as beneficial to health and are being continuously used in the treatment of various diseases. Therefore, it is imperative that a doctor educates the public and creates an awareness of the required amount of neutraceuticals that can be safely used. The future of neutraceuticals is bright and can transform healthcare in a developing country like India which utilizes a large number of natural compounds. PMID- 27190826 TI - Effect of Silybin on Lipid Profile in Hypercholesterolaemic Rats. AB - INTRODUCTION: Hyperlipidemia is a major cause of atherosclerosis and atherosclerosis associated conditions, such as Coronary Heart Disease (CHD), ischaemic cerebrovascular disease and peripheral vascular disease. Though there are hypolipidemic drugs available, the search for a more efficacious hypo lipidemic agent was always going on. AIM: To study the effect of Silybin on lipid profile in Hypercholesterolaemic rats. MATERIALS AND METHODS: After grant of permission from animal ethics committee, the animals were divided into four groups of eight each (normal control, Experimental control with High cholesterol diet, High cholesterol diet + Silybin 300mg, High cholesterol diet + Silybin 600mg). At the end of 60 days the animals in all the groups were subjected to overnight fasting followed by plasma and liver biochemical analyses. STATISTICAL ANALYSIS: The data were analysed by ANNOVA followed by Duncan's multi range test and the value of p<=0.05 was used as the criterion for statistical significance. RESULTS: The rats fed on high cholesterol diet showed significant increase in serum total cholesterol, Triglycerides, LDL-C and VLDL-C. Treatment with Silybin significantly decreased serum total cholesterol (24%), Triglycerides (21%), LDL-C (24%) in a dose dependent manner. Rats treated with Silybin (300 and 600 mg/kg) showed significant increase in hepatic HDL -C and decrease in other lipid profiles. CONCLUSION: Treatment with Silybin significantly decreased both serum and hepatic total cholesterol, triglycerides, VLDL-C, LDL-C and increased HDL-C at both doses. PMID- 27190825 TI - Assessment of Rationality of Fixed Dose Combinations Approved in CDSCO List. AB - INTRODUCTION: Fixed Dose Combination (FDC) is highly popular in the Indian pharmaceutical market and has been particularly flourishing in the last few years. Though rationality status is not clear, the pharmaceutical industry has been manufacturing and marketing FDCs. AIM: To assess rationality of FDCs enlisted in CDSCO list and marketing in India according to pharmacokinetic (FD) and pharmacodynamic (FD) reasoning and WHO rationality criteria. MATERIALS AND METHODS: In this study, 264 FDCs marketed in India from 2009 to 2014 from CDSCO list 2014 were included. Assessment was done on the basis of following parameters: 1) Year and system of FDC; 2) Dosage form; 3) Number of Active Pharmacological Ingredient (API); 4) Schedule of FDC; 5) The presence of the FDC and its ingredients in the WHO Essential Medicine List 2013 and National Essential Medicine List, India 2011; 6) FD and PK parameters of APIs of combination; 7) PK and PD interaction; 8) Safety parameters of ingredients in combination. Descriptive statistics in terms of frequency counts and percentages were used for variables. RESULTS: Out of total 264 FDCs selected, maximum number of combinations (112) were approved in 2010. System wise selection showed 51 (19.31%) FDCs were from cardiovascular system followed by 46 (17.42%) from pain/musculoskeletal system. Oral dosage form was found to be maximum with 200 (75.75%) combinations. According to schedules, 154 (58.33%) combinations were categorized under schedule H. There were 210 (79.54%) FDCs that had two API which was found to be maximum, whereas, only 3 (1.13%) combinations had 5 API. We could find possible PK and PD interactions in between API of 10 (3.78%) and 73 (27.65%) combinations respectively on basis of standard textbooks and references. Similarly dose reduction in API was seen in 58 (21.96%) FDCs. There were 123 (46.59%) FDCs had chances of increased ADRs due to its API. Out of 264 combinations, 52 combinations were rational (6-9), 75 combinations were semi rational (3-<6) and 137 combinations were found to be irrational (0<3). CONCLUSION: We could reveal that majority of combinations approved in last six years were found to be semi-rational and irrational. It is important to carry out detailed study in this area to establish the fact and increase rationality of combinations. PMID- 27190827 TI - Effect of Morinda citrifolia (Noni) Fruit Juice on High Fat Diet Induced Dyslipidemia in Rats. AB - INTRODUCTION: The medicinal value of Morinda citrifolia L. (commonly known as Noni) has been explored in ancient folk remedies with a wide range of therapeutic utility, including antibacterial, antiviral, antifungal, antitumour, analgesic, hypotensive, anti-inflammatory and immune enhancing effects. AIM: The present study was designed to evaluate the effects of Noni fruit juice on serum lipid profile in high fat diet induced murine model of dyslipidemia. MATERIALS AND METHODS: Hyperlipidemia was induced by feeding a cholesterol rich high fat diet for 45 days in wistar albino rats of either sex (n=8). Noni fruit juice administered at 50mg/kg/day and 100mg/kg/day, per oral, was compared with the standard drug Atorvastatin (10mg/kg/day, oral) fed for the latter 30 days. The blood samples were then sent for complete blood lipid profile, after 30 days of treatment. The data presented as mean +/- SEM was analyzed using one-way ANOVA followed by Tukey's post-hoc test. The p <0.05 was considered as statistically significant. RESULTS: The Noni fruit juice treated group showed a significant decrease in the total cholesterol, triglycerides and very low density lipoprotein - Cholesterol at both the doses when compared to the disease control (p<0.05). However, the decrease in the TC (102.75+/-9.79 mg/dL) and LDL-C (47.87+/-7.47 mg/dL) levels observed with the noni fruit juice at the 50mg/kg dose employed, failed to show a statistical significance when compared to atorvastatin. CONCLUSION: The present study provides evidence for the hypolipidemic activity of Noni fruit juice in high fat diet induced hyperlipidemia in rats. PMID- 27190828 TI - Pulmonary Toxicity of Bleomycin - A Case Series from a Tertiary Care Center in Southern India. AB - Hodgkin's lymphoma is one of the curable cancers and the standard treatment regimen involves combination chemotherapy involving bleomycin. One of the fatal side effect of bleomycin is pulmonary toxicity. Here we present three cases of Hodgkin's lymphoma treated with ABVD chemotherapy who had pulmonary toxicity. All three developed bleomycin induced pulmonary toxicity in the form of pulmonary fibrosis during treatment of the disease. Mode of treatment, severity of the condition and the treatment outcome varied among the three. Two recovered following treatment and one patient died due to irreversible pulmonary damage. Causality assessment using Naranjo's scale gave a score of 7 for case one and three and a score of 6 for case two, both indicating the adverse drug reaction to be a probable bleomycin induced Lung fibrosis. PMID- 27190830 TI - Familial Constitutional Rearrangement of Chromosomes 4 & 8: Phenotypically Normal Mother and Abnormal Progeny. AB - Balanced chromosome translocations carriers mostly do not have recognizable phenotypic expression but may have more risk of recurrent spontaneous abortions &/or children with serious birth defects due to unbalanced chromosome complements. Unbalanced chromosomal rearrangements have variable clinical expression and are rare. We present here a case report of three siblings affected with intellectual disability and minor dysmorphic features of face and limbs, born to a non-consanguineous couple in which mother had 5 abortions. The constitutional chromosome analysis revealed balanced translocation t (4;8) in mother and all the three siblings were karyotypically normal. Chromosomal microarray in one of the probands revealed partial monosomy 8pter-p23 and a partial trisomy 4pter-p16. Phenotypic features were recorded in 3 probands using Human Phenotype Ontology terms to query web-based tool Phenomizer. The harmonized description using globally accepted ontology is very important especially in case of rare genetic conditions and the heterogeneous phenotypes which make it even more challenging. The prevalence of sub-microscopic unbalanced translocations may be under-reported due to lesser use of molecular genetic analysis. The familial expression of abnormal phenotypes including intellectual disability make the individuals candidate for molecular genetic analysis and phenotyping to help defer the status of idiopathic mental retardation and identify sub-entity of genetic condition. PMID- 27190829 TI - beta-Thalassaemia and its Co-existence with Haemoglobin E and Haemoglobin S in Upper Assam Region of North Eastern India: A Hospital Based Study. AB - INTRODUCTION: beta-Thalassaemias are common genetic disorders in the Indian subcontinent and its status has not been well studied in the Upper Assam region of North Eastern India. AIM: The aim of the study was to show the prevalence of beta- thalassaemias and its co-existence with Haemoglobin E and Haemoglobin S in the Upper Assam region of North Eastern India. MATERIALS AND METHODS: A total of 1200 anaemic patients were investigated for beta- thalassaemias. Complete Blood Count (CBC) and High Performance Liquid Chromatography (HPLC) were done for screening. RESULTS: Out of 1200 patients screened, 5.83% beta-thalassaemia trait, 2.33% compound Hb E/beta-Thalassaemia, 1.33% beta-thalassaemia major and 0.42% compound Hb S/beta- thalassaemia were detected. A high incidence of thalassaemia is found among the people of Upper Assam region of North Eastern India. CONCLUSION: The only way to prevent the disease is carrier detection and awareness among the people about it. PMID- 27190831 TI - Dating of Early Subdural Haematoma: A Correlative Clinico-Radiological Study. AB - INTRODUCTION: Determination of post-traumatic interval remains one of the foremost important goals of any forensic investigation related to human crimes. The estimation of time since injury in cases of subdural haemorrhage has been studied only by a few investigators on the histological and radiological front. AIM: The purpose of this study was to determine the post-traumatic interval of Subdural Haemorrhage (SDH) based on Hounsfield Unit measurements (HU) on Computed Tomography (CT) in surviving victims of head injury. MATERIALS AND METHODS: The study included a total of 100 cases of closed head injury with subdural haemorrhage. The Post-traumatic Time Interval (PTI) varied from 0.5 hours to a maximum of 249 hours, with a mean of 54.2 hours. RESULTS: Statistically significant results were obtained between the HU measurements of the SDH and the post-traumatic intervals and were found to be statistically significant. A rough attempt was made to determine the effect of haematoma volume on attenuation and was found out to be statistically insignificant. CONCLUSION: The density of the subdural haematoma decreases with increase in the post-traumatic interval that concurs with the limited number of studies being conducted in the past. We concluded that further sorting of cases could be done according to its age with additional research and uniformity in the methodology. PMID- 27190832 TI - Effect of Communication Skills Training on the Burnout of Nurses: A Cross Sectional Study. AB - INTRODUCTION: One of the factors influencing the burnout of nurses is their difficult and complicated relations with patients and other members of the medical team. Therefore, it is necessary that nurses to be trained on communication skills. AIM: The present research aims to study the effect of communication skills training on the burnout of nurses. MATERIALS AND METHODS: The present research was an experimental study using pretest-posttest method. The subjects included 60 nurses working in Khatamolanbia Hospital in Iranshahr, Sistan and Baluchestan Province, Iran. The subjects were randomly divided into two groups. The required data and information were collected using Jackson and Maslach Burnout Inventory which was filled out by subjects in three steps including before the intervention, at the end of the second session, and one month after the intervention. The intervention included training on communication skills which was carried out for the intervention group as a 2-day workshop for 8 hours within a week. RESULTS: The findings showed that the mean score of frequency and intensity of burnout in the intervention group before the intervention, at the end of the intervention, and one month after the intervention was 39.3+/-6.2 and 61.1+/-8.0, 37.5+/-4.6 and 58.8+/-7.6, and 34.2+/ 4.4 and 54.6+/-7.0, respectively. These changes suggest a significant decreasing trend (p=0.01). On the other hand, mean scores of burnout in the control group showed no significant difference in three steps (p<0.05). CONCLUSION: Since communication skills training is an effective and inexpensive way for reducing the burnout among nurses, it is recommended that this approach to be taken into account by managers in order to reduce the burnout among nurses and improve the quality of healthcare services provided by them. PMID- 27190833 TI - Fundamental Ethical Issues in Unnecessary Surgical Procedures. AB - In clinical practice performing any surgical procedure is inconsistent because all surgical procedures carry definitely some degree of risk. Worldwide every year millions of patients go under knife, but many of them are enduring great pain and shelling out thousands and dollars for surgeries they don't really need. This review work was planned with an intention to focus attention towards it with reporting cited evidences of unnecessary surgical operations and discuss ethical issues concern with it. In present review the references search included standard citations Google scholar, MEDLINE and PUBMED. We also used Google search engine for screening various news concern with highlighting this topic in community and online media. For articles we go through more than 60 articles from worldwide and 12 news media views from Google search in last one year. We used following quotes for their search-unnecessary surgeries, second opinion, ethical issues in unnecessary surgeries. Geographical variations were also kept in view. Our intension was highlighting ethical issues concern with unnecessary surgical operations. Henceforth we excluded such work that does not concern with ethical issues. Unnecessary surgery is that which is medically unjustifiable when the risks and costs are more than the likely therapeutic benefits or relief to the patient based on the patient's lifestyle requirements. To avoid or minimize such interventions basic seeding of ethics in curriculum and strict laws will definitely helpful in clinical practice. In conclusion, our aim was to highlight this major issue and underline need of competency based medical bioethics education in Indian scenario. PMID- 27190834 TI - Protection Provided by Hepatitis B Vaccine in Adult Population of Chaharmahal and Bakhtiari Province, Iran in 2013. AB - INTRODUCTION: Hepatitis B vaccination has been integrated into National Expanded Program on Immunization in Iran since the year 1993 and young adult national vaccination project was done in 2008. So we have three subpopulations with vaccination coverage for hepatitis B and different antibody levels. Consisting of Subpopulation 1 born after 1993, subpopulation 2 born between 1989 and 1993 and receiving vaccination under adult national project, and subpopulation 3 born prior to the year 1989. AIM: The present study was conducted to investigate community protection by hepatitis B vaccine in adult population in an accessible population in Iran and compare vaccination coverage, HBs Ab level, and its effective titration among the three above-mentioned subpopulations. MATERIALS AND METHODS: This cross-sectional study was done on a 3000-individual adult population from all seven counties of Chaharmahal and Bakhtiari province enrolled by clustering. After obtaining written consent and filling out a questionnaire of demographic data and history of hepatitis B vaccination by trained interviewers, necessary blood sample was taken and HBs Ab titration was checked. The data were analysed by chi-square in SPSS 19. The level of significance was considered as 0.05 and effective Ab titration as >= 10. RESULTS: The mean age of the participants was 38.4+/-16.3 years. Of the participants 48.2% had effective titration. For vaccination coverage, 77.4% were unvaccinated, 20% completely vaccinated, and 2.6% incompletely vaccinated with a significant association with effective titration (p<0.001). Eighty six percent of the subpopulation 1 and 79% of the subpopulation 2 were completely vaccinated, with a significant difference in effective titration between them (p<0.001). Vaccination coverage was higher in men and the single but equal in cities and villages. The effective titration was significantly associated with being married and residence place (p=0.003). There was a significant association between effective titration and the time at vaccination (p<0.001). CONCLUSION: Protection provided by hepatitis B vaccine in adult population is relatively suitable especially in the youth population; however, catch-up programs of the groups exposed to risk are recommended. PMID- 27190836 TI - Metabolic Syndrome among Secondary School Teachers: Exploring the Ignored Dimension of School Health Programme. AB - INTRODUCTION: The rising trend of obesity, insulin resistance, metabolic abnormalities, pro atherogenic factors are important determinants of both the non communicable diseases and metabolic syndrome. Employees especially school teachers have chronic stress which predisposes them to metabolic syndrome (MS). Thus, increasing the possibility of premature mortality due to CVD and T2DM and escalating the health care cost is affecting their families. AIM: To assess the prevalence and the risk factors influencing metabolic syndrome among secondary school teachers. MATERIALS AND METHODS: A cross-sectional study among secondary school teachers of Mysore city. A self administered, pretested and structured questionnaire based on the WHO Steps Approach for NCD evaluation. Data was analysed in SPSS version 20, chi-square test for categorical variables and t-test for continuous variable was applied along with logistic regression analysis to determine the independent predictors of MS. RESULTS: The prevalence of MS was 115 (38.3%). It increased from 6 (14.3%) in 21-30 years to 40(56.3%) in > 50 years age group. However, 144(48.0%) had '<= two risk factors, 121(40.3%) had >= 3 risk factors and 7(2.3%) had all the five risk factor. CONCLUSION: All components of MS were statistically significant in their association with the metabolic syndrome disease complex. The School health programme can be utilised as an opportunity to screen the teachers and provide primary preventive care. PMID- 27190835 TI - Effect of Probiotic Dietary Intervention on Calcium and Haematological Parameters in Geriatrics. AB - INTRODUCTION: Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. Sufficient calcium intake has been reported to support bone growth and prevent bone loss during the ageing process. AIM: To determine the effect of Lactobacillus helveticus MTCC 5463 probiotic dietary intervention on serum calcium & haematological parameters in geriatric population. MATERIALS AND METHODS: Healthy volunteers with age ranging from 64-74 years were recruited from the nearby residential areas in and around Anand, Gujarat. Study duration was from 2012 to 2015. Of the 112 subjects initially enrolled in the trial, 36 withdrew before the intervention because of not matching with criterias. Of the 76 participants, 5 subjects (4%) under test group and 12 subjects (11%) under placebo left the study. We had 59 subjects who successfully completed a double blind cross over trial. Probiotic fermented milk products (in form of "Lassi") was prepared by supplementing toned milk with honey and fermenting with probiotic Lactobacillus helveticus MTCC 5463 and Streptococcus thermophilus MTCC 5460. The final product had at least 10(8) CFU/ml of viable Lactobacillus helveticus MTCC 5463 at the time of feeding. During feeding period, 200 ml of fermented product containing the test strain to one group and a similar product but without the test strain as placebo were fed regularly at the time of breakfast in morning for 4 weeks. Subjects of each group were given a washout period of 4 weeks before they were crossed over and included to the other group. The study was approved by institutional ethics committee. RESULTS: The socio-demographic and clinical profiles were similar at baseline. The mean (SD) calcium level improved significantly in test {9.36 (0.45) vs 8.45 (0.61), p<0.001}. No significant effect was observed with respect to haemoglobin & haematological parameters. CONCLUSION: The well-documented probiotic Lactobacillus helveticus MTCC 5463 confirmed increase in serum calcium level but no effect on haematological parameters when administered to geriatrics. PMID- 27190837 TI - Impact of Mode of Curriculum on Knowledge and Attitudes of Medical Students towards Health Research. AB - INTRODUCTION: Equipping students with skills in medical research should be an integral part of medical education systems. This study is designed to gauge the difference in knowledge and attitudes towards health research between two sets of undergraduate medical students; those enrolled in the new Problem Based Learning (PBL) education system versus those of the conventional Lecture Based Learning (LBL) curricula. MATERIALS AND METHODS: From the 4(th) and 5(th) years of medical university students, 90 participants were recruited from the Aga Khan University (PBL group) and Dow University of Health Sciences (LBL group) and were presented with structured and pre-validated questionnaire. Responses obtained for knowledge and attitudes of each group were recorded on a scale and graduated in percentages to be compared statistically for differences to identify the effectiveness of each curriculum. RESULTS: The score on the knowledge scale for the PBL group was found to be 44.77% against the 31.55% of the LBL students (p-value<0.001). Furthermore, the mean attitude score of AKU students was 72.22% as opposed to the 56.11% of the DUHS participants (p-value<0.001). CONCLUSION: The PBL group achieved significantly higher scores in all aspects than the LBL group, showing healthier attitudes towards health science research along with better knowledge. Hence, the apparent positive influence of PBL curricula on attitudes towards research may be helpful in improving research output of medical students in Pakistan. PMID- 27190838 TI - Spatio-Temporal Pattern of Breast Cancer - Case Study of Southern Karnataka, India. AB - INTRODUCTION: Spatio-ecological study of disease provides a framework to study the interaction of genetic, environmental, social, cultural and behavioural factors on people's health. The occurrence and interaction of these factors are different in different places, giving rise to distinct geographic or spatial variation. Diseases like breast cancer have variation both spatially and temporally. Public health practitioners can use Geographic Information System (GIS) as a visualization tool to effectively present geographic phenomenon and depict it in maps that might remain otherwise undiscovered in tabular form. AIM: To demonstrate how GIS can be used to understand and communicate breast cancer data through spatial visualization techniques. OBJECTIVES: (i) To visualize the Spatial Distribution of Breast cancer incidences by a point map. (ii) To visualize the Temporal distribution of breast cancer incidences by thematic maps for the study period of 2007 -2011. MATERIALS AND METHODS: Total 1090 breast cancer case records collected for the year 2007-2012 were segregated taluk wise for the 29 taluks and geocoded using the address of the patient, creating a point map. ArcGIS 10.2 software was used to prepare thematic map of breast cancer cases. The taluk wise aggregated breast cancer incidence from the year 2007 to 2011 was then attributed into polygon map representing taluks (Base Map). Natural break data classification technique was used to classify the breast cancer incidence data and breast cancer incidences were classified as low, moderate, high and very high. RESULTS: Spatial distribution of breast cancer incidences using thematic mapping methods high incidences were reported in MY_ T24 (Hunsur), MY_ T25 (KR Nagar), MY_27 (Nanjangud), CH_T1 (Chamrajnagar) and CH-T2 (Gundlupet). Temporal maps prepared for the study from 2007 to 2011 showed that Mysore Taluk had very high Incidence level and the same was observed throughout the study period. The taluks which have high and moderate intensities seem to be fluctuating. However, 25 taluks do not fall into very high category during the study period. Taluks such Gundlupet (CH_T2), K R Nagar (MY_T25), Kollegal (CH_T3) have been observed to enter high intensity category during the year 2011 from moderate intensity. It is also observed that Nanjangud (MY_T27) is in high intensity category throughout the study period which might be due to its proximity to Mysore urban. CONCLUSION: Analysis of Breast Cancer in southern Karnataka using GIS has revealed that urban areas of Mysore has the highest risk of breast cancer and the temporal trends reveal that even rural areas with moderate risk are moving towards high risk areas. PMID- 27190840 TI - Testing of Hypothesis in Equivalence and Non Inferiority Trials-A Concept. AB - Establishing the appropriate hypothesis is one of the important steps for carrying out the statistical tests/analysis. Its understanding is important for interpreting the results of statistical analysis. The current communication attempts to provide the concept of testing of hypothesis in non inferiority and equivalence trials, where the null hypothesis is just reverse of what is set up for conventional superiority trials. It is similarly looked for rejection for establishing the fact the researcher is intending to prove. It is important to mention that equivalence or non inferiority cannot be proved by accepting the null hypothesis of no difference. Hence, establishing the appropriate statistical hypothesis is extremely important to arrive at meaningful conclusion for the set objectives in research. PMID- 27190839 TI - Prevalence of Attention-Deficit Hyperactivity Disorder in Students and Needs Modification of Mental Health Services in Shahrekord, Iran in 2013. AB - INTRODUCTION AND OBJECTIVES: In view of the complications of Attention-Deficit Hyperactivity Disorder (ADHD) and significance of its treatment, the present study was aimed to investigate the prevalence of ADHD among elementary school students of Shahrekord and to assess the obstacles preventing patients from accessing mental health services. MATERIALS AND METHODS: In this cross-sectional study, 631 eligible students were selected from elementary school students in Shahrekord County, Iran. Multi-stage stratified random sampling was adopted. Demographic data were gathered and Child Symptom Inventory-4 for parents and teachers was filled out for each student. The students with suspected ADHD were identified, and examined for the association among mental health help-seeking steps. Obstacles to mental health help-seeking were assessed. RESULTS: ADHD prevalence was derived 17.3% and higher among male students (p=0.025). ADHD prevalence was associated with parents' education and occupation. The evaluation and diagnosis rates were significantly associated with gender (p=0.002 and 0.005, respectively). The most prevalent obstacles facing access to mental health services were those relevant to feeling no need (86%), negative expectations of treatment (78%) and mental health system (64%). CONCLUSION: ADHD was highly prevalent among elementary school students. Identifying the patients and examining the existing obstacles of access to mental health system seems necessary. PMID- 27190841 TI - Usage of Plastic Bags and Health Hazards: A Study to Assess Awareness Level and Perception about Legislation Among a Small Population of Mangalore City. AB - INTRODUCTION: Plastic bag users are at risk of number of health hazards. There is paucity of data with regard to awareness of health hazards among general population in India. AIM: This study was done to find out the status of awareness of the health hazards associated with the usage of plastic bags among people and their perception towards the legislation prohibiting the usage of plastic bags. MATERIALS AND METHODS: This cross-sectional study conducted in Mangalore city in August 2013. Data was collected by interviewing any adult member (aged above 18 years) in each of the selected households using an interview schedule. RESULTS: Mean age of the 250 participants was 32.8+/-10.8 years. Majority 160(64%) were females educated up to undergraduate level or above 187(74.8%). Among the participants 216(86.4%) were aware of the health hazards associated with the use of plastic bags. Awareness was significantly more amongst females (p=0.027), well educated participants (p=0.004) and among professionals and semi-professionals (p<0.001). There were 50(20%) participants reusing plastic bags for shopping after initial usage. The cloth bags were used for shopping in place of plastic bags by 13(5.2%) participants. Among the participants 213(85.2%) were aware of the legislation banning the use of plastic bags and out of which 166(77.9%) were in its favour. Semi-professionals and students favoured the ban on plastic bags whereas unskilled and semiskilled workers were against the ban (p=0.01). CONCLUSION: Most of the participants in the settings had the awareness of hazards of plastic bag usage. However, there is a need for spreading the awareness of using alternative strategies and effective implementation of legislation in order to minimize the usage of plastics in the community. PMID- 27190842 TI - Comparative Study of Permeatal Sandwich Tympanoplasty and Postaural Underlay Technique. AB - INTRODUCTION: Tympanoplasty is the most common operation performed by an Otolaryngologist right from the period of residency. During the last hundred years various modifications in this surgical technique have come up because of continued efforts made by otologists all over the world to achieve the best surgical outcome. AIM: To compare the graft take up and complications associated with the Permeatal Sandwich Tympanoplasty performed with the use of Otoendoscope and traditional Postaural Underlay technique of Tympanoplasty from 1(st) September 2014 to 30(th) August 2015. MATERIALS AND METHODS: Patients attending the ENT OPD, suffering from Chronic Suppurative Otitis Media (CSOM) were selected on the basis of type of perforation and their workup was done to assess the candidature for tympanoplasty. RESULTS: A total of 100 patients were included in the study and the overall graft take was 92.3% in cases of Permeatal Sandwich technique as compared to 64.58% in the case of postaural underlay technique, with a majority of the failures in the large central perforation group rendering a p = 0.021 for patients operated for Large perforations, p = 0.036 for moderate perforations and p = 0.476 for small perforations. The overall p = 0.000649 which is highly significant. On comparing the complications there were only 2 cases in Permeatal Sandwich Technique compared to 25 cases in Postaural Underlay technique rendering a highly significant p-value 0f 0.000000348. There was a difference in hearing improvement with majority of the cases improving to the range of 16-25 dB in Permeatal Sandwich technique compared to 26-45 dB in Postaural Underlay technique. CONCLUSION: Permeatal Sandwich technique produce much better results when compared with Postaural approach in terms of graft take up, complications and hearing improvement. PMID- 27190843 TI - Spindle Cell Carcinoma of Nasal Cavity- A Case Report. AB - Spindle Cell Carcinoma (SpCC), also known as Sarcomatoid Carcinoma, is a rare and peculiar biphasic malignant neoplasm that occurs mainly in the upper aero digestive tract, mostly in larynx. SCC accounts for 3% of all squamous cell carcinomas (SCCs) in the head and neck region. It is a rare variant of SCC which shows spindled or pleomorphic tumour cells simulating a true sarcoma. We present a case report of SpCC nasal cavity in a 50-year-old female patient, presented with intermittent epistaxis from left nasal cavity. On physical examination, the patient had an ulcero-exophytic type of mass in the left nasal cavity and a smooth bulge on the left side of anterior hard palate. Patient underwent excision of nasal mass along with partial palatectomy by facial degloving approach and reconstruction of palate with naso-labial flap. The postoperative histopathological report showed SCC. Surgery forms the mainstay of treatment. Radiotherapy and Chemotherapy is warranted in order to improve treatment results. As only few cases have been reported, we report a case of this rare entity to contribute for better understanding and awareness of this rare malignancy. PMID- 27190844 TI - Vagal Schwannoma: A Rare Parapharyngeal Tumour. AB - Among the parapharyngeal tumours, salivary gland tumours are the commonest, followed by schwannomas, which are slow growing benign tumours. Half of the parapharyngeal schwannomas originate from the vagus. Complete surgical excision is the treatment of choice. We hereby present two cases of parapharyngeal schwannomas, one which had presented as an intraoral mass and the other as a swelling in the neck. The first case, a 57-year-old female patient complained of a slowly increasing swelling in the left side of the throat since 3 months, associated with pain and dysphagia. In the Contrast Enhanced CT scan of the neck, a well-defined cystic lesion with central enhancing solid components (4cm X 4.5cm X 3cm) was seen in the left parapharyngeal region. The second case, a 39-year-old male patient complained of a painless, gradually increasing swelling below the lobule of the right ear since one month. Examination revealed a solitary, nontender, firm and mobile swelling of 2cm X 2cm below the lobule of the right ear. In Contrast Enhanced CT scan of the neck, an enhancing lesion was seen involving the right parapharyngeal space, post-styloid compartment. Both the patients underwent trans-cervical surgical excision. Vagal nerve schwannoma is rare. The majority of the cases present with a slow growing neck swelling without neurological deficit. Complete surgical excision of the tumour is important to prevent recurrence. PMID- 27190845 TI - Benign Lymphoepithelial Cyst of the Parotid in HIV Negative Patient. AB - Benign lymphoepithelial cysts are slow growing tumours commonly seen in HIV positive adults. It is rare to find them in non HIV individuals. In this article we discuss an uncommon presentation of a parotid swelling occurring in a 49-year old non HIV male, which was diagnosed as benign lymphoepithelial cyst. The various investigative modalities and treatment options are outlined in this article. PMID- 27190846 TI - A Rare Case of Angiofibroma Arising from Inferior Turbinate in a Female. AB - A rare case of extranasopharyngeal angiofibroma arising from the inferior turbinate in a young female of 28 years is presented. The case is discussed in light of scant contemporary literature on the cited subject. This clinical record highlights the distinct clinical nature of Extranasopharyngeal angiofibroma (ENA) and importance of Immunohistochemistry in diagnosis of such lesions. With this case we report a rare clinical entity which presented in an extremely rare manner. PMID- 27190847 TI - Role of Frequency Doubled Nd: Yag Laser in Treatment of Corneal Neovascularisation. AB - INTRODUCTION: Cornea is the outermost transparent coat of eye along with sclera, for which its avascularity is essential for maintaining its transparency to have normal visual acuity. Corneal neovascularization is characterized by the invasion of new blood vessels into the cornea from the limbus interfering with corneal transparency, resulting in reduction in visual acuity. It also increases the risk of graft rejection. So their being a dire need to treat corneal neovascularisation, with laser photocoagulation being an effective means of treating it. AIM: To evaluate the efficacy and safety of frequency doubled Nd:Yag laser photocoagulation in treatment of corneal neovascularisation. MATERIALS AND METHODS: A single centre prospective study was carried out on patients attending the outpatient department of ophthalmology in Maharani Laxmi Bai Medical College, Jhansi. Forty eyes of 40 patients having corneal neovascularisation with quiescent eyes satisfying the inclusion criteria were selected and treated with laser. The efficacy of the procedure was noted in terms of area of corneal neovascularisation, status of treated vessels, area of corneal opacity, visual acuity. The above parameters of selected patients were recorded before treatment and subsequent follow up visits at 1 week, 1 month, 2 month and 3 month after laser. Paired t-test was used to calculate the p-value. RESULTS: There was a statistically significant difference in the percentage mean area of corneal neovascularisation with a pre laser value of 31.93% to 17.62% after 3 months of laser treatment (p-value<0.0001). The percentage mean area of corneal opacity decreased from 30.75% to 23.74% (p<0.0001). Out of 185 corneal vessels, 99 (53.51%) vessels were completely occluded,17(9.18%) vessels were partially occluded and 69(37.29%) vessels were recanalised at the end of 3 months after laser treatment. CONCLUSION: Frequency doubled Nd:Yag laser is an effective and safe method for the treatment of corneal neovascularisation. PMID- 27190848 TI - Analysis of Intraoperative and Postoperative Complications in Pseudoexfoliation Eyes Undergoing Cataract Surgery. AB - INTRODUCTION: Pseudoexfoliation (PXE) is a genetically inherited condition affecting usually seen in those aged over 50 years. Surgical management of cataract in patients with PXE pose a challenge due to associated changes in ocular structures. AIM: To study the challenges in the management of cataract in patients with PXE. MATERIALS AND METHODS: This was an interventional study conducted in the Ophthalmology Department of MS Ramaiah Medical College and Memorial Hospital, Bangalore from June 2012 to September 2014. All patients admitted for cataract surgery during this period who were diagnosed as cataract associated with PXE above 50 years of age belonging to either sex were included in the study. All patients underwent cataract surgery with intraocular lens implantation. Depending on type of cataract both small incision and phacoemulsification operations were conducted. Intraoperative and postoperative complications were studied. The patients were reviewed up to 6 weeks postoperatively. RESULTS: A total of 50 eyes of 50 patients diagnosed as cataract with PXE underwent cataract surgery. Of which 40 eyes (80%) underwent small incision cataract surgery whereas, 10 (20%) underwent phacoemusification. Corneal thinning (<535 microns) was noted in majority of the cases (41 cases). Preoperatively there were 3 cases of zonular weakness. Pseudo exfoliation with glaucoma was seen in 5 cases. Intraoperative complications encountered during surgery were; zonular dialysis in 3 cases, posterior capsular tear in 2 cases, out of these 5 cases vitreous loss was seen in 3 cases. Postoperative complications were corneal odema in 17 cases, of which endothelium de-compensated in one case, while early posterior capsular opacification was seen in 6 cases. Final best corrected visual acuity was between 6/6-6/12 in 39(78%) eyes, 6/18 6/36 in 6(12%) cases; 6/60 to less in 5(10%) cases. CONCLUSION: Cataract surgery in eyes with PXE has higher incidence of intraoperative and postoperative complications. A complete preoperative workup helps reduce intraoperative complications and maximises the postoperative results. As corneal thinning is more common a pre-operative pachymetry is desirable to prevent underdiagnoses of glaucoma. PMID- 27190849 TI - Vision Screening of School Children by Teachers as a Community Based Strategy to Address the Challenges of Childhood Blindness. AB - INTRODUCTION: Early detection and treatment of vision problems in children is imperative to meet the challenges of childhood blindness. Considering the problems of inequitable distribution of trained manpower and limited access of quality eye care services to majority of our population, innovative community based strategies like 'Teachers training in vision screening' need to be developed for effective utilization of the available human resources. AIM: To evaluate the effectiveness of introducing teachers as the first level vision screeners. MATERIALS AND METHODS: Teacher training programs were conducted for school teachers to educate them about childhood ocular disorders and the importance of their early detection. Teachers from government and semi-government schools located in Ludhiana were given training in vision screening. These teachers then conducted vision screening of children in their schools. Subsequently an ophthalmology team visited these schools for re-evaluation of children identified with low vision. Refraction was performed for all children identified with refractive errors and spectacles were prescribed. Children requiring further evaluation were referred to the base hospital. The project was done in two phases. True positives, false positives, true negatives and false negatives were calculated for evaluation. RESULTS: In phase 1, teachers from 166 schools underwent training in vision screening. The teachers screened 30,205 children and reported eye problems in 4523 (14.97%) children. Subsequently, the ophthalmology team examined 4150 children and confirmed eye problems in 2137 children. Thus, the teachers were able to correctly identify eye problems (true positives) in 47.25% children. Also, only 13.69% children had to be examined by the ophthalmology team, thus reducing their work load. Similarly, in phase 2, 46.22% children were correctly identified to have eye problems (true positives) by the teachers. By random sampling, 95.65% children were correctly identified as normal (true negatives) by the teachers. CONCLUSION: Considering the high true negative rates and reasonably good true positive rates and the wider coverage provided by the program, vision screening in schools by teachers is an effective method of identifying children with low vision. This strategy is also valuable in reducing the workload of the eye care staff. PMID- 27190850 TI - Correlation of Retinal Nerve Fiber Layer Thickness and Axial Length on Fourier Domain Optical Coherence Tomography. AB - INTRODUCTION: The assessment of the peripapillary Retinal Nerve Fiber Layer (RNFL) thickness has been an important tool for evaluating and diagnosing glaucoma and its progression. Literature suggests that myopic eyes are at an increased risk for developing glaucoma. This study gives an insight into the relationship of RNFL thickness to the axial length in normal population. AIM: To correlate the RNFL thickness and the axial length in normal individuals with Fourier domain Optical Coherence Tomography (OCT). MATERIALS AND METHODS: In the current study, 298 eyes of 149 normal individuals (10 years or older) with or without refractive error were recruited. The RNFL thickness was measured using Optovue (RTVue) three-dimensional Fourier domain OCT. RESULTS: We observed an inverse relationship between average RNFL thickness and increasing axial length(p=0.003). Maximum RNFL thickness was seen in the Infero-Temporal (IT) quadrant and minimum in the Supero-Nasal (SN) quadrant. RNFL thickness did not show any tendency to decline with age using the Pearsons correlation (r=0.07). Females had an increased RNFL thickness in the Supero-Temporal (ST) and Infero Nasal (IN) quadrant (p-value 0.046 and 0.02) in comparison to males. There was a statistically significant thinning in Ganglion Cell Complex (GCC) with increasing axial length (p-value 0.000). CONCLUSION: The current study suggests that the average RNFL thickness does not decrease with age. The RNFL and GCC thickness shows an inverse correlation with axial length of the eyeball hence observations have to be carefully interpreted in myopic eyes. Clinicians need to keep the anatomical variations in RNFL for better patient management. PMID- 27190851 TI - Role of Optical Coherence Tomography in Assessing Anterior Chamber Angles. AB - INTRODUCTION: Gonioscopy is the gold standard in assessing anterior chamber angles. However, interobserver variations are common and there is a need for reliable objective method of assessment. AIM: To compare the anterior chamber angle by gonioscopy and Spectral Domain Optical Coherence Tomography (SD-OCT) in individuals with shallow anterior chamber. MATERIALS AND METHODS: This comparative observational study was conducted in a rural tertiary multi speciality teaching hospital. A total of 101 eyes of 54 patients with shallow anterior chamber on slit lamp evaluation were included. Anterior chamber angle was graded by gonioscopy using the shaffer grading system. Angles were also assessed by SD-OCT with Trabecular Iris Angle (TIA) and Angle Opening Distance (AOD). Chi-square test, sensitivity, specificity, positive and negative predictive value to find correlation between OCT parameters and gonioscopy grading. RESULTS: Females represented 72.7%. The mean age was 53.93 +/-8.24 years and mean anterior chamber depth was 2.47 +/- 0.152 mm. Shaffer grade <= 2 were identified in 95(94%) superior, 42(41.5%) inferior, 65(64.3%) nasal and 57(56.4%) temporal quadrants. Cut-off values of TIA <= 22 degrees and AOD <= 290 MUm were taken as narrow angles on SD-OCT. TIA of <= 22 degrees were found in 88(92.6%) nasal and 87(87%) temporal angles. AOD of <= 290 MUm was found in 73(76.8%) nasal and 83(83%) temporal quadrants. Sensitivity in detecting narrow angles was 90.7% and 82.2% for TIA and AOD, while specificity was 11.7% and 23.4%, respectively. CONCLUSION: Individuals were found to have narrow angles more with SD-OCT. Sensitivity was high and specificity was low in detecting narrow angles compared to gonioscopy, making it an unreliable tool for screening. PMID- 27190852 TI - Concurrent Infections of Conidiobolus Coronatus with Disseminated Tuberculosis Presenting as Bilateral Orbital Cellulitis. AB - Zygomycetes species contains two orders of organisms that infect humans, namely Mucorales and Entomophthorales. Entomophthorales cause chronic infection in immunocompetent patients, invading subcutaneous tissues but are non angioinvasive. This includes Basidiobolus ranarum, Conidiobolus incongruus and Conidiobolus coronatus. We report a case of disseminated tuberculosis with Conidiobolus coronatus infection presenting as orbital cellulitis in an adolescent. PMID- 27190853 TI - Sebaceous Gland Carcinoma of Eyelid- A Tarnished Masquerade. AB - Malignant tumours of the face are usually seen in the periocular region, mainly on eyelids most commonly in the inferior eyelid, medial canthus and superior eyelid, respectively. The prime treatment for eyelid malignant tumours is the total excision of the lesion with frozen section control or by Mohs Micrographic surgery. The postoperative defects should be reconstructed judicially taking care that the near normal anatomical and functional recovery is achieved. The Cutler Beard flap procedure, a good alternative in the reconstruction of superior near total eyelid defects resulted in good restoration of anatomy and function in our patient. We report a case of an eyelid growth persisting for 2 year duration mimicking a chalazion. Clinically the eyelid mass had malignant features and hence was planned for wide excision with frozen section of margins. After confirming the tumour free margins, we performed reconstruction of the eyelid defect with Cutler Beard flap procedure. She was followed up for one year which showed no local recurrence or regional/distant metastases. PMID- 27190854 TI - Adult Rhabdomyosarcoma of Ethmoid Sinus Recurring as an Orbital Mass. AB - Alveolar rhabdomyosarcoma (RMS) is a primitive, malignant, round cell neoplasm derived from mesenchymal tissue that exhibits partial skeletal muscle differentiation. We describe a rare case of alveolar RMS of ethmoid sinus, recurring as an orbital mass. A 23-year-old man with the chief complaint of anosmia and mild proptosis was diagnosed with RMS of the left ethmoid sinus and orbit following an endoscopic biopsy of the mass. He was treated with chemotherapy and radiotherapy. At 12 months after diagnosis, while still on maintenance chemotherapy, he presented to our eye hospital with a large medial canthal mass and lateral globe displacement. Orbital computed tomography revealed an extraconal mass in the medial orbit of the left eye, extending posteriorly and compressing the medial rectus muscle. Notably, the ethmoid sinus was clear. Incisional biopsy was performed and the recurrence of alveolar RMS was confirmed. Alveolar RMS of the ethmoid sinus may recur as an orbital mass, even if the sinus where it originated is clear at the time of recurrence. PMID- 27190855 TI - A Rare Presentation of Two Cases of Metallic Intrascleral Foreign Body Entry through Upper Eyelid. AB - Ocular injury secondary to foreign body remains an important cause of ocular morbidity with or without blindness in working population. Intraocular foreign body may have varied clinical presentation. Initially it may look an apparently normal eye followed by obvious ocular symptoms depending upon its location and degree of inflammation. It can result in partial or full thickness penetration of sclera with or without involvement of posterior segment. We hereby present two cases of metallic intrascleral foreign body entry through upper lid in young carpenters following hammer and chisel injury. In case 1, Intrascleral location of foreign body was confirmed with X ray orbit and B scan ultrasonography while in case 2 the diagnosis of intrascleral foreign body was missed at the first visit to ophthalmology clinic Both the patients underwent exploratory surgeries where intrascleral metallic foreign bodies were found without ocular penetration. An intrascleral foreign body may be missed due to small penetrating scleral wound covered by a large subconjunctival haemorrhage accompanied by minimal or no signs of inflammation and failure on part of treating ophthalmologist to suspect an intrascleral foreign body. To establish a diagnosis of intraocular particularly intrascleral foreign body, careful history taking and clinical examination along with use of imaging studies are mandatory steps which help in successful management and good visual outcome. These cases highlight the importance of considering a presumptive diagnosis of retained intrascleral foreign body in every patient with a history of penetrating ocular trauma through lid or a visible wound/scar on the lid. PMID- 27190856 TI - Christmas Tree Cataract - A Cataract that Glitters. PMID- 27190857 TI - Evaluation of the Symptom of Constipation in Indian Patients. AB - INTRODUCTION: The exact prevalence of constipation in India is unknown. To know this, first it has to be properly defined based on stool frequency and form (as in western definition) in Indian patients, data on which is scarce. There may be difference with the western definition also. AIM: To determine the stool frequency and form in patients consulting doctor for the complaint of constipation and compare these with the Western definition of constipation. MATERIALS AND METHODS: This was a prospective cross-sectional study on 331 consecutive patients seeking medical advice for their complaint of constipation. They were administered a questionnaire containing Rome III criteria points of functional constipation and constipation predominant irritable bowel syndrome and the Bristol stool chart to report their predominant stool form. Organic bowel diseases were excluded by further history taking, physical examination and appropriate investigations. The data on stool frequency and form thus obtained were compared with the existing Indian population data. RESULTS: A total of 65% patients were above 60 years of age. The predominant stool types were 1-3 according to Bristol stool form scale present in 93.8% patients and conformed to Asian criteria of constipation by stool form. Only 67.9% patients passed Bristol Stool Scale (BSS) type 1 and 2 stool which is the western definition. 51.5% reported a frequency of 3-4 motions/week, 19.8% had normal stool frequency by Indian standard (i.e. at least 1 motion/day) and only 35.4% had constipation by Western criteria (less than 3 motions/week). Hence subjective feeling varied widely from observed rate and Western definition was invalid in about twothird of patients. Feeling of incomplete evacuation was universal and this was referred to as constipation by patients. Functional constipation was diagnosed in 69.1% (of whom most were elderly with co-morbidities) and constipation predominant irritable bowel syndrome in 13.8% by Indian standard. Only 2.1% had colonic cancer. CONCLUSION: A stool frequency of <5 motions/week appears more appropriate in Indian definition of constipation where the subjective feeling of incomplete evacuation should also be given due weightage. Asian criteria based on stool form holds true in India. PMID- 27190858 TI - Basic Risk Factors Awareness in Non-Communicable Diseases (BRAND) Study Among People Visiting Tertiary Care Centre in Mysuru, Karnataka. AB - INTRODUCTION: Non Communicable Diseases (NCDs) are the major causes of mortality and morbidity globally. Awareness about NCDs and their risk factors has an important role in prevention and management strategies of these NCDs. AIM: 1) To assess the awareness of risk factors contributing to NCDs among the patients visiting tertiary care hospital in Mysuru district; 2) To compare the difference in awareness of risk factors for NCDs among the urban and rural patients with/ without NCD visiting the tertiary care hospital. MATERIALS AND METHODS: A cross- sectional study was conducted in a tertiary care centre- JSS Hospital, Mysuru, Karnataka from March 2013 - August 2013. The patients visiting Medicine OPD during the period were the study subjects. The subjects were allocated into 4 groups: Urban without any NCD, Urban with atleast one NCD, rural without NCD, rural with atleast one NCD. A pretested questionnaire regarding awareness of risk factors for NCDs was used in the study and frequency and proportions were used to analyse the data. RESULTS: A total of 400 subjects, 100 subjects in each group were included in the study. Out of these subjects about 65% of the urban group and 42% of the rural group subjects were aware of the NCDs and their risk factors. Least awareness was observed among the rural subjects without any NCDs (35%). CONCLUSION: The awareness of risk factors of NCDs and knowledge regarding prevention of NCDs was not satisfactory. The results highlighted the need and scope for health education and interventions to improve the awareness about NCDs and their risk factors. PMID- 27190859 TI - Level of Satisfaction Among People Living with HIV (PLHIV) Attending the HIV Clinic of Tertiary Care Center in Southern India. AB - INTRODUCTION: Patient satisfaction is an important issue for the health care sector. Hospitals routinely collect patient satisfaction data so that they can improve the quality of their services. There is a dearth of research in the field of satisfaction among people living with HIV (PLHIV) in India. AIM: The aim of our study was to determine the level of satisfaction among PLHIV attending the HIV clinic of tertiary health centre in Southern India. MATERIALS AND METHODS: This descriptive cross-sectional study was done in the HIV clinic attached to Kasturba Medical College (KMC) Hospital, Mangalore, India from August 2012 - August 2013. PLHIV of age more than 18 years were included. During the study period 422 consecutive patients who consented for the study were enrolled. To determine patient satisfaction towards healthcare service, we used the Short Form Patient Satisfaction Questionnaire (PSQ-18). Data was analysed using SPSS Version 11.5 statistical software. RESULTS: A total of 422 patients were included in the study out of whom 253(60%) were males and 169(40%) were females. Mean age of the patients was 37.08+/-7.2 years. The median CD4 count was 345 cells/mm(3) (IQR 245 451.2). The mean score for general satisfaction was 4.43+/-0.48, for technical quality 4.77+/-0.26, for interpersonal manner 4.59+/-0.4, for communication 4.64+/-0.42, for financial aspects 3.20+/-0.78), for accessibility and convenience 4.50+/-0.72 and for time spent with the doctor was 4.59+/-0.45. Subscale scores for general satisfaction, technical quality, accessibility, interpersonal manner, finance and communication were higher in females when compared to males which were found to be statistically significant. Younger PLHIV (<= 35 years) had significantly higher scores in technical quality, interpersonal manner and time spent with the doctor when compared to older PLHIV. CONCLUSION: Patient satisfaction was highest for technical quality and it was lowest for financial aspects. If hospitals wish to improve the quality of health services they should give priority to decreasing costs and improving accessibility. PMID- 27190860 TI - The Study of Gonadal Hormonal Abnormalities and Sexual Dysfunction in HIV Positive Females: An Exploratory Study. AB - INTRODUCTION: Every endocrine gland has been reported to be affected at varying rates in HIV. HIV is a highly stigmatized chronic disease with a substantial co occurrence of mental and sexual health problems; however the sexual health problems in women have not been extensively studied. AIM: To study the gonadal hormonal abnormalities and sexual dysfunction in HIV positive female patients and its possible association. MATERIALS AND METHODS: This descriptive/exploratory study was conducted in the Department of General Medicine at a tertiary care hospital from September 2013 to August 2015. The study group included 50 diagnosed HIV-positive patients. They were also subjected to specific questions regarding sexual dysfunction by female counselors using female sexual function index. Visits of the subjects were scheduled independent of the menstrual cycle. Hormonal levels (free testosterone, FSH, LH) were measured. RESULTS: Out of 50 patients, 26 patients in our study had sexual dysfunction (52%). Patients with age group between 30-39 years had the maximum sexual dysfunction compared to the other groups (<0.001). Patients with a CD4 count between 200 and 499 had the maximum sexual dysfunction (<0.02). Mean duration of HIV in the study was 30 months in sexual dysfunction group which was significant (p<0.005). Hormonal levels were found to be in normal range. All the study patients reported desire, arousal and lubrication problems whereas orgasm and satisfaction problems were noted in 60% patients with pain reported in 52%. CONCLUSION: We identified that although the hormonal levels were in the normal range, they were comparatively in the lower range in the dysfunction group than the non-dysfunctional group. Both free testosterone and FSH levels were low indicating involvement of the pituitary rather than the gonads. We also conclude that duration of HIV and also level of CD4 count is related to sexual dysfunction. PMID- 27190861 TI - Complications in Advanced Diabetics in a Tertiary Care Centre: A Retrospective Registry-Based Study. AB - INTRODUCTION: Diabetes is a major public health problem in our country and complications of diabetes are a major cause of morbidity and mortality. There is a need to quantify the complications in order to improve our strategies for prevention and management. AIM: To measure the prevalence of complications in type 2 diabetics following up at a tertiary care centre and to study its association with the socio-demographic and clinical parameters. MATERIALS AND METHODS: A retrospective record based study was conducted on 3261 type 2 diabetic patients on insulin therapy, recorded in the diabetic registry maintained at Goa Medical College from Aug 2009 to May 2012. Data on anthropometric measurements, demographic characteristics, complications and other details were extracted from these records. RESULTS: Out of the 3261 patients 1025 (31.4%) had macrovascular complications and 1122 (34.4%) had at least one microvascular complication. The prevalence of peripheral vascular disease, coronary artery disease and stroke were 6.7%, 21.3% and 6.6% respectively and were significantly higher in males. The prevalence of diabetic retinopathy, nephropathy and neuropathy were 16.7%, 16.5% and 16.3% respectively with diabetic nephropathy being significantly higher in males. Trend analysis showed significant association of rising prevalence of all complications with age (p<0.05). Duration of diabetes also showed significantly positive trend for all complications (p<0.05) except stroke. CONCLUSION: The study presents the prevalence of diabetic complications in patients reporting to a tertiary hospital in Goa. Coronary artery disease was found to be the most common complication. As age and duration of diabetes were found to be significantly associated, efforts should be made towards promoting earlier diagnosis of diabetes so as to improve management and decrease the chances of complications. PMID- 27190863 TI - Utility of Cell-Block of Bronchial Washings in Diagnosis of Lung Cancer- A Comparative Analysis with Conventional Smear Cytology. AB - INTRODUCTION: Bronchoscopy is a safe & effective means of diagnosing bronchogenic carcinoma with a varying diagnostic yield of different bronchoscopic procedures. Cell-Block (CB) preparation of cytology specimen has been shown to increase the diagnostic yield further. To the authors' knowledge, the diagnostic value of CB as an adjunct to conventional smear cytology (CS) of bronchial washing specimens in the detection of bronchogenic carcinoma has not been well evaluated. AIM: The present study was aimed to evaluate the diagnostic utility of CB of bronchial washings when compared with CS. MATERIALS AND METHODS: A total of 104 patients of suspected bronchogenic carcinoma were subjected to bronchoscopy as per British Thoracic Society (BTS) protocol. Bronchial biopsy, brushings and washings were collected. Smears were prepared immediately of bronchial washings and another aliquot was subjected to CB preparation and further processing by paraffin embedding and H&E staining. RESULTS: Out of 104 patients, 92 were diagnosed by bronchoscopy with a cumulative diagnostic yield of all sampling techniques being 88.46%. Yield of CB of bronchial washings (44.23%) was higher than Bronchial washings - conventional smears (36.53%). CB detected additional 8 cases of malignancy where corresponding bronchial washings-conventional smears were negative. Exclusive diagnosis by CB was obtained in 2 cases. Brushings and biopsy confirmed malignancy in 49.03% and 57.69% cases. CONCLUSION: CB of bronchial washings had a higher yield as compared to corresponding conventional smears. Increase in yield was also noted when CB of bronchial washings was combined with biopsy and compared to bronchial washings- conventional smears combined with biopsy. In limited resource settings, CB preparation is a simple method that increases diagnostic yield of flexible bronchoscopy, is cost effective & hence can be routinely used. The immunohistochemical and molecular studies are possible with CB only, which is a distinct advantage over conventional smears of bronchial washings. PMID- 27190862 TI - Ascitic Fluid High Sensitive C-Reactive Protein (hs-CRP). A Prognostic Marker in Cirrhosis with Spontaneous Bacterial Peritonitis. AB - INTRODUCTION: C-Reactive Protein (CRP) is an acute phase reactant. Its level increases in the presence of acute or chronic inflammation and infections. High sensitive CRP (hs-CRP) is more sensitive than CRP as an inflammatory marker. High sensitive CRP has been known to be elevated in chronic liver diseases and Spontaneous Bacterial Peritonitis (SBP). AIM: The aim of the study was to establish the role of ascitic fluid high sensitive C-reactive protein (hs -CRP) as a prognostic indicator in patients with SBP. MATERIALS AND METHODS: A total of 100 patients with decompensated cirrhosis admitted in medicine ward and ICU were included, of which 50 patients of acute bacterial peritonitis were used as study group and 50 patients of sterile ascites were used as control group. Hs-CRP level of cases and controls were estimated. SBP cases were treated with its standard recommended antibiotic therapy and hs-CRP level was again estimated after 5 days of antibiotic therapy or at the time of discharge. RESULTS: The mean level of hs CRP before antibiotic therapy of the patients with SBP was significantly higher than that of the patients without spontaneous bacterial peritonitis (t98=17.72; p=0.0001). The mean level of hs-CRP at 5(th) day or discharge after initiation of antibiotic therapy was significantly lower than that of level of hs-CRP before initiation of antibiotic therapy (p<0.05). The mean hs-CRP of the cases with poor outcome (death and prolonged hospital stay) was significantly higher than others. CONCLUSION: Ascitic fluid hs-CRP level can be considered as a surrogate prognostic marker in cases of Cirrhosis with SBP. PMID- 27190864 TI - Budd- Chiari Syndrome as an Initial Manifestation of Systemic Lupus Erythematosus. AB - Budd- Chiari syndrome is caused by obstruction of hepatic venous outflow. There are numerous causes for Budd-Chiari syndrome. One of the causes is systemic lupus erythematosus due to antiphospholipid antibodies. Only few cases have reported Budd-Chiari syndrome as an initial manifestation of systemic lupus erythematosus (SLE). This is a case report of Budd-Chiari syndrome due to SLE. PMID- 27190865 TI - A Case of Pleuroparenchymal Metastasis: Rare Aetiology. AB - A phyllodes tumour is a malignancy of both mesenchymal and epithelial origin affecting the breast. The malignant course of this breast tumour causing lung metastasis is rare. Here we report a treated case of borderline phyllodes tumour that presented with pleuroparenchymal metastasis. Our case highlights the possibility of recurrence of borderline phyllodes tumour as pleuroparenchymal metastasis even after a long disease free interval. PMID- 27190866 TI - Idiopathic Pulmonary Fibrosis and Myasthenia Gravis: An Unusual Association. AB - Idiopathic Pulmonary Fibrosis (IPF) is a chronic fibrosing lung condition with high morbidity and mortality, accounting for about 25% of the cases of interstitial lung diseases. It usually has a progressive course resulting in death due to respiratory failure. Myasthenia Gravis (MG) is an autoimmune neuromuscular disease, caused by antibody mediated activity against acetylcholine receptor at the neuromuscular junction. It is characterized by fluctuating muscle weakness and fatigue. Extensive literature search did not reveal any case report of an association between these two conditions. Here we present a case of a patient with IPF who also developed MG. The diagnosis of IPF was based on High Resolution Computed Tomography (HRCT) of the lung and that of MG was based on clinical criteria and electrophysiological testing. The case was successfully managed. PMID- 27190867 TI - Isolated Right Ventricular Infarction Mimicking Anterior ST-Segment Elevation. AB - Acute coronary syndromes in patients with presence of ST-segment elevation in the anterior precordial leads indicates left anterior descending coronary artery occlusion. However, anterior ST-segment elevation has also been described in right ventricular myocardial infarction and is thought to be due to right coronary artery (RCA) occlusion. We present a rare case of isolated RVMI presenting with anterior ST-segment elevation due to proximal occlusion of a right coronary artery that was treated by primary coronary angioplasty. Primary coronary angioplasty and stenting of this artery was performed resulting in resolution of the chest pain and ST- segment elevation. PMID- 27190868 TI - Intravenous Immunoglobulin Responsive Persistent Thrombocytopenia after Dengue Haemorrhagic Fever. AB - Dengue outbreak is common in Indian subcontinent and causes significant morbidity and mortality. Year 2015 has witnessed yet another Dengue epidemic in northern India and the number of cases this year is maximum in a decade. Dengue infection is a viral disease and there are 4 different serotypes DENV1, DENV2, DENV3 and DENV4. This year DENV2 and DENV4 have been isolated from most of the patients. Thrombocytopenia is hallmark of dengue infection and generally recovers within ten days of onset of symptoms. We report a case of dengue haemorrhagic fever in which thrombocytopenia persisted for almost a month and improved after Intravenous immunoglobulin (IVIG) administration. This is the first case where IVIG has been successfully used for treating persisting thrombocytopenia after dengue infection. PMID- 27190869 TI - Combined Arterial and Venous Thrombosis in Ulcerative Colitis- A Rare Vascular Manifestation. AB - Combined arterial and venous thrombosis in patients with ulcerative colitis is a rare extra vascular manifestation, which motivated the current report. Increased coagulability is a recognised feature of ulcerative colitis with frequency increasing during flares. We report the case of a 42-year-old lady who was a diagnosed case of ulcerative colitis, currently in remission. She presented with swelling followed by discolouration of left lower limb which later was diagnosed as deep venous thrombosis combined with femoral and popliteal artery thrombosis. This led to wet gangrene of the limb, sepsis, septic shock and death despite aggressive management with heparin infusion, ionotropes, and parenteral antibiotics therapy. PMID- 27190870 TI - Biphasic Effect of Rifampicin on Bilirubin- A Case Report. AB - Drug induced hepatitis is a major problem which a physician encounters in his clinical practice. In view of increasing incidence of tuberculosis in our country a large number of infected individuals are started on Antituberculous (ATT) drugs and rifampicin is invariably part of the regimen. One of the major adverse effects of ATT drugs is drug- induced hepatitis which is characterized by elevation of liver enzymes and bilirubin. Hepatotoxicity is usually idiosyncratic or dose-dependent. Rifampicin causes transient elevation of transaminases in 10 20 percent of individuals and this does not warrant dose adjustments of the drug. Rarely rifampicin can lead to severe hepatitis with hyperbilirubinaemia and marked elevations of SGOT and SGPT and in some patients this can be fatal. The exact mechanism of Rifampicin induced hepatotoxicity is not known but it is postulated to be due to idiosyncratic reaction to rifampicin metabolites which may be directly toxic or induce an immunologically mediated liver injury. Rarely rifampicin may cause hyperbilirubinaemia without enzyme elevation. Here we report a patient with bilateral pulmonary tuberculosis who developed transient severe indirect hyperbilirubinaemia on rifampicin. On review of relevant literature we find that rifampicin can have a biphasic effect on bilirubin, an initial increase in indirect bilirubin and later normalization of bilirubin. We have reported this case because of its rarity in clinical practice. PMID- 27190871 TI - Scrub Typhus Presenting with Bilateral Lateral Rectus Palsy in A Female. AB - Scrub typhus, a rickettsial disease is endemic in several parts of India usually presenting with acute symptoms. Fever, maculopapular rash, eschar, history of tick exposure and supportive diagnostic tests usually leads to diagnosis. Scrub typhus should be included in the differential diagnosis in occasions when a patient presents with fever with or without eschar and isolated cranial nerve palsy. Here we are reporting a case of Scrub typhus who presented with fever and altered sensorium of short duration, eschar formation and bilateral lateral rectus palsy. Patient was treated with doxycycline with complete reversal of neurodeficit. PMID- 27190872 TI - An Unusual Case of HCV Negative Cryoglobulinemia Presenting as Symmetrical Peripheral Gangrene. AB - Cryoglobulins are monoclonal or polyclonal immunoglobulins that undergo reversible precipitation at low temperatures. Cryoglobulinemia is associated with HCV infection in more than 90% cases, the remaining 10% being called as Essential Cryoglobulinemia which is generally associated with a severe course and suboptimal response to conventional therapies. As the digital vessels are more prone to colder temperatures, hyperviscosity in those vessels can initiate local thrombosis and may manifest as ischemic ulceration and gangrene. We report here a very unusual case of HCV negative cryoglobulinemic vasculitis presenting as symmetrical peripheral gangrene of fingers and toes. PMID- 27190873 TI - Delayed Diagnosis of Graves' Thyrotoxicoisis Presenting as Recurrent Adrenal Crisis in Primary Adrenal Insufficiency. AB - Adrenal crisis is a potential life threatening complication. The common causes of adrenal crisis are infections, surgical stress and abrupt cessation of steroid medications. Endocrine causes like Graves' disease with thyrotoxicosis is one of the less common causes of an adrenal crisis. We report a 42-year-old female who presented with recurrent episodes of adrenal crisis due to delayed diagnosis of thyrotoxicosis. She was initially treated with Carbimazole followed by Radio iodine ablation and currently she is euthyroid. Her adrenal insufficiency was initially treated with hydrocortisone during the time of adrenal crisis followed by Prednisolone 5 mg once daily in the morning along with fludrocortisone 50 mcg once daily. This case highlights the need for high index of suspicion and less common causes like thyrotoxicosis should be ruled out in patients with adrenal crisis. PMID- 27190874 TI - Correspondence: Ebola Virus Disease in ASEAN Countries. PMID- 27190875 TI - Red Eye and Red Face Following Defibrilation. PMID- 27190876 TI - Effect of Gender on the Total Abdominal Fat, Intra-Abdominal Adipose Tissue and Abdominal Sub-Cutaneous Adipose Tissue among Indian Hypertensive Patients. AB - INTRODUCTION: Abdominal obesity is a better marker of adverse metabolic profile than generalized obesity in hypertensive subjects. Further, gender has effect on adiposity and its distribution. AIM: Effect of gender on obesity and the distribution of fat in different sub-compartments of abdomen among Indian hypertensive subjects. MATERIALS AND METHODS: This observational study included 278 adult subjects (Males-149 & Females-129) with essential hypertension from a tertiary care centre in north India over one year. A detailed history taking and physical examination including anthropometry were performed in all patients. Total Abdominal Fat (TAF) and abdominal adipose tissue sub-compartments like Intra-Abdominal Adipose Tissue (IAAT) and Sub-Cutaneous Adipose Tissue (SCAT) were measured using the predictive equations developed for Asian Indians. RESULTS: Female hypertensive subjects had higher Body Mass Index (BMI) with more overweight (BMI >= 23kg/m(2)), and obesity (BMI>= 25 kg/m(2)). Additionally, they had higher prevalence of central obesity based on both Waist Circumference (WC) criteria (WC>= 90 cm in males and WC>= 80 cm in females) and TAF criteria {>=245.6 cm(2) (males) and >=203.46 cm(2) (females)} than male patients. But there was no difference in the prevalence of central obesity based on Waist Hip Ratio (WHR) criteria (WHR >=0.90 in males and WHR >= 0.85 in females) between two genders. High TAF & IAAT were present in more females although there was no difference in the distribution of high SCAT between two genders. CONCLUSION: Female hypertensive subjects were more obese with higher abnormal TAF & IAAT compared to male patients. However, there was no difference in the distribution of high SCAT among them. PMID- 27190878 TI - Strangulated Groin Hernia Repair: A New Approach for All. AB - INTRODUCTION: The available classical approaches for Groin hernia are multiple. The change of approach with change of incision is needed with these approaches when the bowel is gangrenous. AIM: To evaluate the efficacy and safety of a new approach for all strangulated groin hernias (inguinal, femoral and obturator), in terms of change of approach/complications. MATERIALS AND METHODS: It was conducted in surgical unit-2 of MGM Hospital, Kakatiya Medical College Warangal, Telangana State, India, from Nov 2000 to Oct 2010. Total 52 patients operated with classical approach were compared with 52 patients operated present new approach. All the cases (52+52) were with gangrenous bowel which required resection and end to end anastomosis of bowel. All the cases (52+52) were managed with mesh repair and the results were analysed. RESULTS: In classical approach: Three cases required laparotomy (5.7%). Twelve cases required change of approach with change of incision (23%). Eight cases developed wound infection after mesh repair (15%). Four cases required removal of mesh (7.6%). Two Cases developed recurrence (3.8%). In present new approach: No laparotomy (0%), no change of incision (0%), no removal of mesh (0%) and no recurrence(0%). Only 2 cases (3.8%) developed wound infection at lateral part of incision ie. p<0.05. CONCLUSION: This new approach for all - gives a best approach for strangulated groin hernias as it is easy to follow. It obviates the change of incision and need for a laparotomy. It further retains normal anatomy, prevents contamination of the inguinal canal and permits a mesh repair leading to decreasing the chances of recurrence. PMID- 27190877 TI - Validation of Selection Criteria for Active Surveillance in Prostate Cancer. AB - INTRODUCTION: Considerable Proportion of Prostate Cancer (PCa) patients suitable for Active Surveillance (AS) harbour aggressive disease at surgical histopathology. Identification of truly indolent prostate cancer at diagnosis is difficult. AIM: Of this study was to evaluate the accuracy of current AS protocols in identifying low risk PCa by comparing the histopathology at biopsy and surgery. MATERIALS AND METHODS: A retrospective study was performed on all patients who underwent Radical Prostatectomy (RP) between 2008 and 2012. We identified patients who fulfilled inclusion criteria of five different established AS protocols. Histopathology at biopsy was compared with final surgical histopathology to identify upgrading or upstaging of disease. The biochemical recurrence rate in the cohort was also determined. RESULTS: A total of 59 patients (24%) met criteria of at least one protocol. Sixteen patients (28%) were eligible for AS based on all studied criteria. Overall 24 patients (40.6%) were upgraded in their final histopathology while 12 patients (20%) upstaged from their original TRUS biopsy. Two patients (3%) had PSA failure, both had salvage radiotherapy. CONCLUSION: There is considerable discrepency in current AS selection criteria which makes it necessary to introduce novel markers to identify indolent disease as a part of AS protocol for PCa. PMID- 27190879 TI - Comparison of the Effects of Varicocelectomy and Oral L-carnitine on Sperm Parameters in Infertile Men with Varicocele. AB - BACKGROUND: Varicocele is defined as dilated and twisted veins of the pampiniform plexus in the spermatic cord. It is the most common cause of male infertility. There are various medical and surgical procedures for the treatment of this disease. AIM: This study was aimed to compare the effects of oral administration of L-Carnitine and varicocelectomy on spermogram parameters. MATERIALS AND METHODS: This study was conducted as a double blind clinical trial without randomization. Inclusion criteria were, all married infertile men with varicocele. Patients chose their treatment personally and spermogram was carried out for all patients before and after the third and sixth months of treatment. Then, the sperm parameters of the two groups were compared using repeated measures ANOVA. RESULTS: In our study, trend of sperm count in the surgery group changed from 22 to 28.61 million (vs 34.6 to 45.37 in L-Carnitine group), motility changed from 21.74 to 35.38 percent (vs 33.9 to 47.48 in L-Carnitine group), normal sperm morphology changed from 46.25 to 60 percent (vs 56.61 to 69.7 in L-Carnitine group) and volume of semen changed from 3.5 to 4.17 cc (vs 2.95 to 4.33 in L-Carnitine group). These values were not statistically different between the two groups. CONCLUSION: Based on the results of this study, we can say that medicinal treatment by administration of oral L-Carnitine is as effective as varicocelectomy in improving semen parameters and can be used as an alternative to surgery for varicocele grade II. PMID- 27190880 TI - Association between Hyperglycaemia with Neurological Outcomes Following Severe Head Trauma. AB - INTRODUCTION: Head Trauma (HT) is a major cause of death, disability and important public health problem. HT is also the main cause of hyperglycaemia that can increase mortality. AIM: The aim of this study was to assess the correlation between hyperglycaemia with neurological outcomes following severe Traumatic Brain Injury (TBI). MATERIALS AND METHODS: This is a descriptive and correlation study that was carried out at the Imam Khomeini Hospital affiliated with Ilam University of Medical Sciences, Ilam, IR, during March 2014-March 2015 on patients with severe TBI. Data were collected from the patient records on mortality, Intensive Care Unit (ICU) length of stay, hospital length of stay, admission GCS score, Injury Severity Score (ISS), mechanical ventilation, Ventilation Associated Pneumonia (VAP) and Acute Respiratory Distress Syndrome (ARDS). Random Blood Sugar (RBS) level on admission was recorded. Patients with diabetes mellitus (to minimize the overlap between acute stress hyperglycaemia and diabetic hyperglycaemia) were excluded. RESULTS: About 34(40%) of patients were admitted with hyperglycaemia (RBS >= 200 mg/dl) over the study period. The mortality rate, length of ICU stay, hospital stay, ISS and VAP & ARDS in patients with RBS levels >= 200 mg was significantly higher than patients with RBS levels below <= 200mg (p<0.05, p<0.001). A significant correlation was found between RBS with GCS arrival, length of ICU stay, length of hospital stay, ISS, mechanical ventilation and VAP & ARDS (p<0.05, p< 0.001). RBS is a predicate factor for ISS (p <0.05, OR : 1.36), GCS (p <0.001, OR : 1.69), mechanical ventilation (p< 0.05, OR : 1.27), VAP & ARDS (p <0.001, OR : 1.68), length of ICU stay (p <0.001, OR : 1.87) and length of hospital stay (p <0.05, OR : 1.24). CONCLUSION: Hyperglycaemia after severe TBI (RBS >= 200) is associated with poor outcome. It can be a predictive factor for mortality rate, ICU stay, GCS arrival, VAP & RDS, hospital stay and ISS. Management of hyperglycaemia with insulin protocol in cases with value >200mg/dl, is critical in improving the outcome of patients with TBI. PMID- 27190881 TI - Sinister Splenic Artery Pseudoaneursym: A Rare Case of Unidentified Aetiology. AB - Splenic Artery Pseudoaneurysms (SAP) are very rare. Giant SAPs are those which are more than 5 cm in diameter and are rarer. SAPs are usually caused by pancreatitis, trauma, surgery or other iatrogenic interventions, vasculitis, local infective or inflammatory processes. We report the successful surgical management of a giant SAP of unidentified aetiology. This case report highlights the significance that this entity may present atypically and hence, early recognition and aggressive management may be life saving. PMID- 27190882 TI - Delayed Diagnosis of Left-Sided Diaphragmatic Hernia in an Elderly Adult with no History of Trauma. AB - Diaphragmatic Hernia (DH) is the herniation of abdominal contents into the thorax through a rent in the diaphragm. Acquired DH most commonly occurs following a blunt or penetrating trauma to the abdomen with former being common than the later. Very rarely DH can be spontaneous and be asymptomatic until it's very extensive. A 78-year-old presented with breathlessness and chest pain of one month duration. There was dull note to percussion and absent breath sounds in left lower zone. Auscultation revealed bowel sounds in left infra-axillary and mammary area. Electrocardiogram and laboratory data suggested acute myocardial infarction. Coronary angiogram showed a triple vessel disease. Roentgenogram was simulating pneumonic consolidation but presence of air shadows was the thing against pneumonic consolidation. CT imaging of the thorax revealed an extensive left diaphragmatic hernia with viscera and left kidney as its contents. He was initially taken up for CABG and surgery for diaphragmatic hernia was planned at a later date. This case is important for its extensive nature and for its rarity as acquired DH rarely occurs spontaneously. Chest roentgenogram must be read cautiously in all such cases to look for this entity. Auscultation for bowel sounds in the thorax is a diagnostic clue. PMID- 27190883 TI - Acute Urinary Retention due to Primary Pelvic Hydatid Cyst: A Rare Case Report and Literature Review. AB - Causes of urinary retention in old men include benign prostatic hyperplasia, prostatitis, prostate cancer, Scarring of the urethra or bladder neck as a result of injury or surgery, use of certain medicines particularly NSAIDs and opioid analgesics, constipation and neurogenic bladder. When the above common causes are not quite obvious by clinical examination and relevant investigations, then it is necessary to think of other rare diseases. It is with the above in our mind that a case of bladder outflow obstruction due to a large primary retrovesical hydatid cyst is herein reported in a 58-year-old man. Ultrasonography (USG) and Contrast Enhanced Computed Tomography (CECT) scan of the abdomen and pelvis of the patient revealed a large, multilocular, nonenhancing, cystic lesion in the rectovesical pouch having typical cartwheel appearance without any other intraabdominal organ involvement. These typical radiological characteristics led us to suspect the presence of a hydatid cyst. He underwent exploratory laparotomy where cystopericycstectomy was done. Pre-operative and post-operative albendazole prophylaxis was also given. In conclusion, hydatid cyst should always be considered in the differential diagnosis of pelvic cystic masses, specially in endemic regions. PMID- 27190885 TI - Ileo-Colic Burkitt Lymphoma in a Young Adult Female- A Case Report. AB - Burkitt's lymphoma is an uncommon and aggressive type of Non-Hodgkin's lymphoma and is one of the fastest growing cancer tumour in humans; growth fraction close to 100%. We report a case of a young adult female presented with acute pain abdomen with ileo-caecal mass. On clinical presentation, initial diagnosis was acute appendicitis with lump formation. Ultrasound reported as diffuse inflammatory changes and later CECT was done which reported as Gastro-Intestinal Stromal Tumour (GIST). On laparotomy, a huge hard mass was found on ileo-caecal region and right hemicolectomy was done. Diagnosis was confirmed as Non-Hodgkins Burkitt's Lymphoma by HPE and immunohistochemistry testing. So, careful workup is the key to initiate early treatment. This patient had complete remission after the right hemicolectomy followed by multiagent chemotherapy. PMID- 27190884 TI - Perforated Gastric Gangrene without Pneumothorax in an Adult Bochdalek Hernia due to Volvulus. AB - Bochdalek hernia is the most frequent congenital diaphragmatic hernia which occurs due to a defect in the posterior attachment of the diaphragm when there is a failure of closure of the pleuroperitoneal membrane in utero. It rarely presents for the first time in adults. We report one such case of a 23-year-old male patient who presented with an acute abdomen. Chest X-ray showed air under diaphragm and he was taken up for an emergency laparotomy. Intraoperatively an organoaxial volvulus of the stomach was found in a bochdaleks hernia with a focal gangrene of the stomach fundus with perforation and peritonitis. However, there was no breach of pleural cavity. A sleeve resection of the gangrenous portion of the stomach was performed and the diaphragmatic defect was repaired. Patient made an uneventful postoperative recovery. Gastric gangrene with perforation as a manifestation of the adult bochdalek hernia is indeed rare. A concomitant pneumothorax occurs along with this condition which requires an intercostal drainage tube prior to the laparotomy. We report this case for its unique presentation without pneumothorax. PMID- 27190886 TI - Unusual Finding in the Inguinal Canal: Abdominal Tuberculosis Presenting as Inguinal Hernia. AB - Abnormal findings in the inguinal canal during Herniotomy are not very rare for a paediatric surgeon. These abnormal findings may range from opposite gender sex organ (e.g. uterus and fallopian tube during orchidopexy) to unexpected malignancy (e.g. Rhabdomyosarcoma) to the abnormal embryological development (Splenogonadal fusion). Though abdominal tuberculosis is common, abdominal tuberculosis presenting as an inguinal hernia is exceedingly uncommon. We report an unusual case of abdominal tuberculosis presenting as inguinal hernia. PMID- 27190888 TI - Ainhum - A Rare Case Report. AB - The term 'AINHUM' is derived from the African word meaning 'to saw or cut'. True ainhum otherwise called dactylolysis spontanea is a condition involving soft tissue or digits with constricting rings commonly presenting in fifth toes, usually bilateral. It is to be differentiated from Pseudo-ainhum that occurs secondary to some hereditary and nonhereditary diseases that lead to annular constriction of digits. We report a rare case of true ainhum involving the left fourth toe only. It is a very rare case and a very few were reported worldwide. The highest incidence of ainhum has been reported in South Africa and South America. It is rarely reported in India. Ainhum when diagnosed and treated in early stages can be prevented from progressing to mutilating deformities. PMID- 27190887 TI - Treatment of Resistant Cyclophosphamide Induced Haemorrhagic Cystitis: Review of Literature and Three Case Reports. AB - Haemorrhagic Cystitis (HC) is defined as diffuse inflammatory bladder bleeding due to many aetiologies. Massive HC often arises from anticancer chemotherapy or radiotherapy for the treatment of pelvic malignancies. Phosphamides are the anti cancer drugs used for treating breast cancer, B-cell lymphoma, leukemia, rheumatoid arthritis and systemic lupus erythaematosis by cross-linking strands of DNA and preventing the cell division. They are also used in bone marrow transplantation for prevention of Graft Versus Host Disease (GVHD). Hepatic metabolism of phosphamide forms acrolein, and acrolein makes ulceration, haemorrhage, edema and necrosis of the urothelium during its excretion by the urine. Infectious causes of HC in immunocomprimesed patients are adenovirus, BK polyoma-virus (BK), JC virus, and Cytomegalovirus (CMV). The present article attempts to make a review of literature for the treatment of intractable HC and report three cases with HC. PMID- 27190889 TI - Successful Treatment of a Large Pelvic Abscess Using Intraluminal VAC: A Case Report. AB - The most feared complication of the surgical treatment of rectal cancer is anastomotic leakage, which is related to high rates of mortality and morbidity. Here, we present a patient who could not be treated with surgical drainage but treated by intraluminal Vacuum Associated Closure (VAC). A 34-year-old male patient was treated for rectal cancer by low anterior resection, colorectal anastomosis, and diverting ileostomy following neoadjuvant CRT. The patient reported with a postoperative anastomotic disruption and a large pelvic abscess. Due to the continuation of foul-smell drainage inspite of perianal incision and drainage, intraluminal VAC was applied and the pelvic abscess and the foul-smell were successfully treated. The presence of an adequate anal sphincter tonus is a disadvantage in anastomotic leakage, since it prevents the emptying of the intestinal content and also precludes the drainage of the pelvic abscess. The endoluminal application of VAC, similar to the results of application of VAC in open wounds, has been demonstrated to decrease fibrin and necrotic tissue in the pelvic cavity and increase granulation tissue. VAC, which has long been used in the treatment of open wounds, is a promising method in the treatment of large pelvic abscesses due to anastomotic leakage following rectum resection. PMID- 27190891 TI - Bowel Herniation Through 5mm Port Site: An Unusual Complication. AB - Trocar site herniation is a rare complication following laparoscopic surgery. We report a case of small bowel herniation through 5mm port site following laparoscopic myomectomy. A 36-year-old lady underwent laparoscopic myomectomy. On the fourth postoperative day she developed features of intestinal obstruction. Further evaluation with CT scan showed herniation of a loop of small bowel through the 5mm port site in right iliac fossa. Surgical exploration of the port site revealed a herniated loop of viable small bowel. The enlarged facial defect was closed after reduction of the bowel. Patient recovered uneventfully. Bowel herniation through 5mm port site is a rare complication which requires prompt diagnosis and immediate treatment to avoid morbidity. PMID- 27190890 TI - Anastomotic Leakage in a Patient with Acute Intestinal Obstruction Secondary to Appendiceal and Ileal Endometriosis: A Case Report. AB - Endometriosis is a commonly encountered problem in women of reproductive age. It usually causes chronic abdominal pain. However, it rarely causes complications such as intestinal obstruction. The most commonly performed procedure for these patients is bowel resection and anastomosis. Unless it is complicated with anastomotic leakage. We present a 39-year-old woman presented with intestinal obstruction due to appendiceal and ileal endometriosis complicated with anastomotic leakage after surgery. PMID- 27190892 TI - An Unusual Lesser Sac Collection Causing Gastric Outlet Obstruction with Coincidental Occurrence of Leriche's Syndrome: A Case Report. AB - Gastric outlet obstruction in adults is usually caused by pyloric stenosis secondary to peptic ulcer disease or malignancy. However, there are few other causes such as a foreign body and external compression due to pseudocyst pancreas. We present a rare aetiology of a large collection of pus in the lesser sac in our patient causing gastric outlet obstruction. A perforated peptic ulcer was suspected in our patient who had symptoms of sudden onset pain in epigastric region which was referred to back. This was followed by pain in upper abdomen, vomiting, constipation and fever for which patient was being managed conservatively before being referred to us. The CECT didn't show any leakage of contrast to the lesser sac making the possibility of healed perforation likely as all other causes were ruled out at the time of presentation to our hospital. The CECT scan ruled out other causes of gastric outlet obstruction with normal wall thickness of the stomach and duodenum along with normal looking liver, pancreas and no lymphadenopathy. The liver function tests and serum amylase were within normal limits. Along with this, there was another unrelated rare coincidental finding of aortoiliac occlusive disease termed as Leriche's syndrome. Ultrasound guided percutaneous drainage was done following which the patient's obstruction was relieved and patient was referred to the department of vascular surgery for the mangement of aortoiliac occlusive disease. PMID- 27190893 TI - Macrodystrophia Lipomatosa of the Toe: A Rare Case Report. AB - Macrodystrophia lipomatosa is a rare congenital hamartoma presenting as a localized or generalized gigantism of a limb or digit manifesting from infancy to late adulthood. It is a progressive enlargement of the soft tissue components, especially fibrofatty tissue. The patient presents to us because of cosmetic reasons or mechanical issues secondary to degenerative joint disease, or features of neurovascular compression due to large osteophytes. Here, we present a case of this anomaly of the left second toe with complaints of difficulty in walking and wearing shoes, for which toe reduction surgery with partial amputation was done. PMID- 27190894 TI - Tiger Food for Short Bowel: Two Cases. PMID- 27190895 TI - Human Chorionic Gonadotropine in Cul-de-sac Fluid in Tubal Ectopic Pregnacy; A New Diagnostic Approach. AB - INTRODUCTION: Although new diagnostic abilities are being utilised increasingly yet early detection of tubal pregnancy remains a challenge. The use of highly sensitive hCG kits has facilitated the early diagnosis of a pregnancy. But it takes time to determine the localisation of the pregnancy. Early diagnosis of ectopic pregnancy may reduce the morbidity of ectopic pregnancy. AIM: This study was conducted to analyse the cul-de-sac and serum betahCG ratio in tubal ectopic pregnancy cases which may be a new diagnostic approach for ectopic pregnancy. MATERIALS AND METHODS: Between January 2004 and July 2011, 263 patients with ectopic pregnancy were included in the study. Risk factors of patients and treatment modalities were evaluated. hCG was measured in peripheral serum and peritoneal fluid, obtained by puncture of Douglas pouch in 52 patients with tubal ectopic pregnancy. hCG level was determined in the cul-de-sac fluid and in the maternal serum for comparison. RESULTS: Tubectomy (5.3%), history of abortion (9.5%), history of previous surgery (14.8%), previous cesarean section (8%) and pelvic infamatorry disease (15.9 %) were the important risk factors for ectopic pregnancy in our cases. In 51 of 52 patients with tubal pregnancy, the cul-de-sac hCG vaule and the serum hCG value ratio was >1. CONCLUSION: It is concluded that the ratio of hCG in cul-de -sac and serum can be used for the verification of tubal ectopic pregnancy in addition to other diagnostic methods. This may help rapid confirmation of the diagnosis of ectopic pregnancy. PMID- 27190896 TI - The Effect of Combined Antenatal and Postnatal Counselling on Postpartum Modern Contraceptive Use: Prospective Case-Control Study in Kocaeli, Turkey. AB - INTRODUCTION: The integration of family planning education into obstetric care has been suggested to increase postpartum contraception use. However, ideal time and type of counseling is controversial. There is no prospective study about combining prenatal and postnatal education on the postpartum modern contraceptive use (PPMC). AIM: This study was aimed to explore the effects of the addition of postpartum contraceptive counselling to antenatal education on PPMC. MATERIALS AND METHODS: Family planning counselling was given to all participating patients throughout antenatal care (ANC) via brief communications. After delivery, the women were categorised into two age-matched groups with a 1:1 allocation ratio in the order of the birth date. No further intervention was performed for Group I (n: 98). Women in Group II (n: 102) received further contraceptive education at six weeks after hospital discharge. Six months after delivery, PPMC was compared between the two groups. RESULTS: PPMC was similar between Group I and II (p>0.05). Previous contraceptive experiences, obstetric care service intensity and partner's support were the factors related to postnatal contraceptive use. Logistic regression analysis showed that PPMC was independent of confounding factors in each group. CONCLUSION: The addition of postnatal counseling to antenatal one did not further increase PPMC. The results of this study suggested that family planning counseling should be provided antenatally. PMID- 27190897 TI - Evaluation of Clinical Diagnosis of Fetal Distress and Perinatal Outcome in a Low Resource Nigerian Setting. AB - INTRODUCTION: Fetal distress has been shown to contribute to the increasing caesarean section rate. There has been controversy on the usefulness of clinical diagnosis of fetal distress using only the intermittent counting of the fetal heart rate and/or passage of meconium-stained liquor. AIM: To evaluate the clinical diagnosis of fetal distress and the perinatal outcome. MATERIALS AND METHODS: This was a retrospective study in which the case records of the patients, who were diagnosed of fetal distress at Federal Teaching Hospital, Abakaliki, Nigeria, from January 1, 2008 to December 31, 2014, were collated. The statistical analysis was done using the Statistical Package for Social Sciences version 17 software (SPSS Inc., Chicago IL, USA). RESULTS: Out of the 15,640 deliveries carried out within the study period, 3,761 (24.05%) deliveries were through caesarean section. A total of 326 (8.9%) of the 3,761 caesarean sections were due to fetal distress within the study period. More so, a total of 227 (70.9%) babies were born with >= 7 Apgar score at the 1(st) minute of delivery. The perinatal mortality rate was 31.25 per 1000 deliveries. Though birth asphyxia was recorded more on babies of mothers that had fresh meconium-stained liquor and whose decision-intervention interval was more than 30 minutes when compared with those without any of the two conditions, there was no statistical significant difference between them. CONCLUSION: The clinical diagnosis of fetal distress is accurate in 29.1% of the cases. However, it has led to an unnecessary caesarean section in the remaining 70.9% of the parturients. In order to reduce this high trend of unnecessary caesarean sections due to clinical diagnosis of fetal distress in this environment, antepartum fetal assessment with non-stress test or biophysical profile and intrapartum use of continuous electronic fetal monitoring should be used to confirm or refute the fetal distress before any surgical intervention. Fetal blood sampling and fetal pulse oximetry should be performed in event of non- re-assuring or abnormal cardiotocography. PMID- 27190898 TI - Effect of Massage Therapy on Duration of Labour: A Randomized Controlled Trial. AB - INTRODUCTION: Massage is an old technique that is widely used in childbirth and can decrease the childbirth pain by reducing the adrenaline and noradrenaline and increasing the endorphins and oxytocin and reduce the childbirth duration by increasing the uterine contractions. Therefore. AIM: This study is aimed to evaluate the effect of massage therapy on the duration of labour. MATERIALS AND METHODS: The present study was performed as randomized controlled clinical trial method on 100 pregnant women referred to maternity ward in Fatemieh Hospital, Shahroud. Subjects with inclusion criteria and who were interested to participate in the study were placed in one of the test or control groups based on pre specified sequence. Questionnaires were completed in several stages. Data analysis was conducted using chi-square test, Fisher's exact test, independent t test, Mann-Whitney test and multivariate linear regression in SPSS-21software. In data analysis, p < 0.05 was considered significant. RESULTS: The results of multivariate linear regression showed that the duration of the first and second stage labour in the massage receiving group is significantly decreased compared to the test group (p= 0.004 and p= 0.02, respectively). In addition, the Apgar scores at minutes 1 and 5 in test group is significantly increased compared to control group (p <0.0001). CONCLUSION: The findings of this study showed that massage therapy during labour will lead to shortening of the first and second stage labour duration and improve Apgar scores at the first and fifth minutes. By shortening the duration of labour, pregnant women tend to have more normal vaginal delivery. PMID- 27190899 TI - Capillary Hemangioma of the Fallopian Tube. AB - Neoplastic lesions of the fallopian tube are rarely seen by surgical pathologists. Haemangioma of the fallopian tube is an extremely rare benign neoplasm. A 30-year-old lady with polymenorrhea and dysmenorrhea underwent hysterectomy and bilateral salpingo-oophorectomy. Her left fallopian tube showed a 2mm sized solid nodule in the wall. Histopathological examination revealed a well-defined vascular lesion in the left fallopian tube, consistent with capillary haemangioma. The vascular endothelium was highlighted by CD34 immunostaining. Our literature review has identified 10 cases of cavernous haemangioma of the fallopian tube. To the best of our knowledge, we report the first ever case of capillary haemangioma of the fallopian tube. This is also the smallest detected haemangioma in the fallopian tube. PMID- 27190900 TI - Gynaecological Perspective of Schwannoma: A Rare Pelvic Tumour. AB - Schwannomas are benign tumours that arise from Schwann cells of nerve fibres. They commonly occur in the head, neck, mediastinum and extremities but pelvic occurrence is rare. We report a rare case of retroperitoneal tumour with Gynaec presentation. A 26-year-old parous woman was admitted with abdominal mass, pain abdomen, painful menstruation and painful coitus for one year. Abdominal examination revealed firm mass filling the lower abdomen with restricted mobility. On bimanual examination cervix was hitched against pubic symphysis. Mass felt through anterior and left adnexa not tender, uterus felt close to the mass about 8-10 weeks size, right adnexa free. USG revealed broad ligament fibroid with cystic right ovary. Hence myomectomy was planned, but intraoperatively it was found that the mass was filling the pelvis close to bulky uterus with cystic right ovary. After informed consent while proceeding with hysterectomy, necrotic, yellow colour material came out from the capsule like structure of the mass which was close to lower part of posterior wall of uterus. Mass was removed except which was adherent to deeper structure left behind. Histopathological examination revealed Schwannoma undergoing cystic degeneration. Since Schwannoma was mostly diagnosed incidentally, high degree suspicion is necessary for diagnosis. PMID- 27190901 TI - Intrinsic Obstetric Palsy: Case Report and Literature Review. AB - Maternal neurological injuries may be intrinsic to the labour and delivery process or may result directly or indirectly from obstetric or anaesthetic intervention. This intrinsic obstetric palsy is a rare complication of labour but can have devastating impact on a previously healthy mother. A 23-year-old gravida1, para0 who had epidural for labour analgesia, was augmented for slow progress and had a normal vaginal delivery. She was diagnosed post delivery with intrinsic obstetric palsy involving several peripheral nerves and lumbosacral nerve roots with a guarded prognosis. In this article we have discussed the risk factors and mechanisms of intrinsic obstetric palsy and proposed further investigation into the potential protective role of ambulatory analgesia i.e. CSE (Combined Spinal Epidural) or LDI (Low Dose Infusion). PMID- 27190902 TI - Screening and Diagnosis of Gestational Diabetes Mellitus, Where Do We Stand. AB - Gestational Diabetes Mellitus (GDM) is defined as any glucose intolerance with the onset or first recognition during pregnancy. This definition helps for diagnosis of unrecognized pre-existing Diabetes also. Hyperglycemia in pregnancy is associated with adverse maternal and prenatal outcome. It is important to screen, diagnose and treat Hyperglycemia in pregnancy to prevent an adverse outcome. There is no international consensus regarding timing of screening method and the optimal cut-off points for diagnosis and intervention of GDM. DIPSI recommends non-fasting Oral Glucose Tolerance Test (OGTT) with 75g of glucose with a cut-off of >= 140 mg/dl after 2-hours, whereas WHO (1999) recommends a fasting OGTT after 75g glucose with a cut-off plasma glucose of >= 140 mg/dl after 2-hour. The recommendations by ADA/IADPSG for screening women at risk of diabetes is as follows, for first and subsequent trimester at 24-28 weeks a criteria of diagnosis of GDM is made by 75 g OGTT and fasting 5.1mmol/l, 1 hour 10.0mmol/l, 2 hour 8.5mmol/l by universal glucose tolerance testing. Critics of these criteria state that it causes over diagnosis of GDM and unnecessary interventions, the controversy however continues. The ACOG still prefer a 2 step procedure, GCT with 50g glucose non-fasting if value > 7.8mmol/l followed by 3 hour OGTT for confirmation of diagnosis. In conclusion based on Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study as mild degree of dysglycemia are associated with adverse outcome and high prevalence of Type II DM to have international consensus It recommends IADPSG criteria, though controversy exists. The IADPSG criteria is the only outcome based criteria, it has the ability to diagnose and treat GDM earlier, thereby reducing the fetal and maternal complications associated with GDM. This one step method has an advantage of simplicity in execution, more patient friendly, accurate in diagnosis and close to international consensus. Keeping in the mind the diversity and variability of Indian population, judging international criteria may not be conclusive, thus further comparative studies are required on different diagnostic criteria in relation to adverse pregnancy outcomes. PMID- 27190903 TI - Uterine Fibroid (Leiomyoma) with Acute Urinary Retention: A Case Series. AB - Uterine leiomyomas are an extremely rare cause of acute urinary retention in women. The delay in diagnosing uterine leiomyomas presenting with acute urinary retention further complicates the management. The rarity of the condition makes it difficult to plan either prospective or retrospective trials. Hence, most of the evidence comes from case reports or series. We report a case series of acute urinary retention in women with uterine leiomyomas and discuss the pathophysiology, diagnosis and management options. PMID- 27190904 TI - Thoracic Endometriosis Syndrome: A Veritable Pandora's Box. AB - Thoracic endometriosis syndrome is a rare disorder characterised by the presence of functioning endometrial tissue in pleura, lung parenchyma, airways, and/or encompasses mainly four clinical entities-catamenial pneumothorax, catamenial haemothorax, catamenial haemoptysis and lung nodules. The cases were studied retrospectively by reviewing the records at Amrita Institute of Medical Sciences, for duration of five years i.e., form March 2010-2014 and analysed for the clinical presentation and management of thoracic endometriosis syndrome. Catamenial breathlessness was the main symptom. Pneumothorax and pleural effusion were the findings on investigations. Histopathology report of endometriosis was present in three cases (50%). Conditions with excess oestrogen like endometriosis, fibroid, adenomyosis were diagnosed in these patients by pelvic scan. After the initial supportive treatment with hormones, pleurodesis, hysterectomy and lung decortication were the treatment modalities. Two cases that had multiple recurrences were diagnosed as disseminated TES. They underwent combined treatment of surgery and hormones. PMID- 27190905 TI - Study of the Clinical Outcome between Traumatic and Degenerative (non-traumatic) Meniscal Tears after Arthroscopic Surgery: A 4-Years Follow-up Study. AB - INTRODUCTION: The meniscus is a biconcave fibrocartilage in the knee joint interpose between the femoral condyles and tibial plateau; the meniscus has functions in load bearing, load transmission, shock absorption joint stability, joint lubrication, and joint congruity. AIM: The aim of this study is to provide orthopeadic surgeon a base of reference in the choice of the optimal course of management for meniscal tears. MATERIALS AND METHODS: One hundred and seventeen patients met the criteria of inclusion for the present study. Patients were divided in two groups T and NT according to the presence of distinct previous traumatic events to the knees. Two subgroups were formed in each groups T and NT respectively at a mean follow up of 1 and 4 years. Postoperative clinical outcome were assessed using Lysholm scores and Rand SF-36 survey. RESULTS: One hundred and seventeen patients were included in the present study with 60(51.28%) patients in the traumatic group and 57(48.71%) in the degenerative group. 95(81.19%) patients in total were satisfied with their health status at end of follow up. The mean value of Lysholm scores at 1 year were respectively 85.25+/ 8.78 for traumatic group and 86.38+/-12.14 for non-traumatic group and at 4 years were respectively 92.63+/-7.31 for traumatic group and 72.90+/-20.77 for non traumatic group. According to Rand SF-36 health, traumatic group showed better improvements compare to non-traumatic group between 1 and 4 years after arthroscopic meniscus surgery. CONCLUSION: A total of 95(81.19%) patients in total were satisfied with their health status at follow up, however, we found that arthroscopy as a treatment for meniscal tear have a relatively better mid term clinical outcome for traumatic meniscal tears compare to non traumatic/degenerative meniscal tears. PMID- 27190906 TI - Evaluation of Vacuum Assisted Closure Therapy for Soft Tissue Injury in Open Musculoskeletal Trauma. AB - INTRODUCTION: The application of controlled levels of negative or sub atmospheric pressure for a prolonged period of time on a wound had shown to accelerate removal of excess fluid and promote hyperaemia, which eventually promote wound healing. AIM: The study was conducted with the aim to evaluate the effectiveness of Vacuum Assisted Closure (VAC) therapy for soft tissue injury in open musculoskeletal trauma. MATERIALS AND METHODS: Twenty cases of complex musculoskeletal wound involving different parts of body were included in this progressive randomized study. In patients, aggressive debridement was done before the application of VAC therapy. Controlled negative pressure was uniformly applied to the wound. Dressings were changed after every 4 to 5 days. The evaluation of results included healing rate of the wound, eradication of infection, complication rate, and number of secondary procedures. RESULTS: VAC therapy over the wound was administered for an average of 20.4 days +/-6.72 days (range 14 to 42 days). There was decrease in wound size attained by VAC therapy ranged from 2.6 to 24.4cm(2), with an average reduction of 10.55 cm(2). Three wounds were infected at the start of VAC therapy. However, all patients were cleared of bacterial infection by the end of VAC therapy. CONCLUSION: VAC therapy using negative pressure promote Wound healing by increasing local capillary perfusion and increased rate of granulation tissue formation, decreases the duration of wound healing and requires fewer painful dressing change. PMID- 27190907 TI - A Study on the Correlation of Pertrochanteric Osteoporotic Fracture Severity with the Severity of Osteoporosis. AB - INTRODUCTION: Osteoporosis is a metabolic bone disease caused by progressive bone loss. It is characterized by low Bone Mineral Density (BMD) and structural deterioration of bone tissue leading to bone fragility and increased risk of fractures. When classifying a fracture, high reliability and validity are crucial for successful treatment. Furthermore, a classification system should include severity, method of treatment, and prognosis for any given fracture. Since it is known that treatment significantly influences prognosis, a classification system claiming to include both would be desirable. Since there is no such classification system, which includes both the fracture type and the osteoporosis severity, we tried to find a correlation between fracture severity and osteoporosis severity. AIM: The aim of the study was to evaluate whether the AO/ASIF fracture classification system, which indicates the severity of fractures, has any relationship with the bone mineral status in patients with primary osteoporosis. We hypothesized that fracture severity and severity of osteoporosis should show some correlation. MATERIALS AND METHODS: An observational analytical study was conducted over a period of one year during which 49 patients were included in the study at HIMS, SRH University, Dehradun. The osteoporosis status of all the included patients with a pertrochanteric fracture was documented using a DEXA scan and T-Score (BMD) was calculated. All patients had a trivial trauma. All the fractures were classified as per AO/ASIF classification. Pearson Correlation between BMD and fracture type was calculated. STATISTICAL ANALYSIS USED: Data was entered on Microsoft Office Excel version 2007 and Interpretation and analysis of obtained data was done using summary statistics. Pearson Correlation between BMD and fracture type was calculated using the SPSS software version 22.0. RESULTS: The average age of the patients included in the study was 71.2 years and the average bone mineral density was 4.9. The correlation between BMD and fracture type was calculated and the r values obtained was 0.180, which showed low a correlation and p-value was 0.215, which was insignificant. CONCLUSION: Statistically the pertrochanteric fracture configuration as per AO Classification does not correlate with the osteoporosis severity of the patient. PMID- 27190908 TI - The Role of Fibular Fixation in Distal Tibial Fractures. AB - INTRODUCTION: Lower tibial extra-articular fractures of lower tibial extra articular bone, treated with Minimally Invasive Percutaneous plate osteosynthesis (MIPPO) may have certain advantages, though the modiality is technically demanding. AIM: To assess the results of distal tibial fractures treated with minimally invasive plate osteosynthesis utilizing precontoured dital medial tibial locking plates without fibular fracture fixation. MATERIAL AND METHODS: The study was conducted during the period from june 2009 to june 2011. A series of 30 patients (22 men and 8 women) with concurrent distal tibia and fibula fractures who underwent minimally plate osteosynthesis utilizing precontoured distal tibial medial locking plates without fibular fracture fixation have been reviewed after surgery. 14 fractures were type A1, 6 type A2, and 4 type A3. Open Grade II fracture were 4 and Open Grade IIIA fracture is2. RESULTS: The mean follow-up duration was 2 years. The mean time to bone union was 20 weeks. No patient had shortening, hardware breakdown, or deep-seated infection. Out of 30 patients, 24 had excellent results, 6 had good results. Four patients had palpable screws, two patient had blisters which subsidized with conservative treatment. This minimally invasive technique for treatment of distal tibial fractures proved to be a feasible and worthwhile method of stabilization. CONCLUSION: It appears from our study that fibula fixation is not required in non syndesmotic distal metaphyseal extra articular fractures when fixed by locking plate using minimal invasive techniques. PMID- 27190909 TI - Hip Pain and Gait Disturbance Associated with Idiopathic Hypoparathyroidism. PMID- 27190910 TI - Cotoneaster: A Safe and Easy Way to Reduce Neonatal Jaundice. AB - INTRODUCTION: Consumption of cotoneaster may reduce neonatal jaundice. AIM: Hence this study was undertaken to determine the effect of mothers' cotoneaster consumption on treatment of their neonates' jaundice. MATERIALS AND METHODS: In this randomized clinical trial study, 120 neonates with jaundice referred to a hospital in southwest Iran were enrolled by nonprobability sampling and divided randomly into four groups. In the first group both mothers and neonates received cotoneaster; in the second group only mothers; in the third group only neonates; and in the fourth group the neonates received distilled water as placebo. Phototherapy was done under the same condition for all neonates. RESULTS: The reduction of bilirubin was significantly higher in treatment groups compared to control group (p<0.05). Bilirubin in the group of neonates whose mothers consumed cotoneaster was less compared to control group at 24 and 36 hours (p<0.05) and the highest reduction in bilirubin was observed in the first group. The mean duration of hospitalization was longer for the control group (p<0.05). CONCLUSION: Consumption of cotoneaster by both mothers and neonates caused a decrease in neonatal jaundice more rapidly compared to other groups and decreased the duration of hospitalization. Cotoneaster consumption by mothers, neonates, or both may be useful in treatment of neonatal jaundice. PMID- 27190911 TI - Is Reactive Dengue NS1Antigen Test a Warning Call for Hospital Admissions? AB - INTRODUCTION: Dengue fever is a major public health problem worldwide. The 2011 revised World Health Organization (WHO) guidelines have emphasized on early diagnosis and intervention to reduce the case fatality rate due to dengue fever. Rapid diagnostic tests like NS1 antigen assays have improved the detection of cases in early clinical phase of illness but its role as a predictor of severe dengue infection is not very clear. AIM: To evaluate the utility of NS1 Ag assay as an early diagnostic marker and predictor of severe dengue infection. MATERIALS AND METHODS: All children (0-12 years of age) diagnosed and confirmed with dengue fever at a tertiary care hospital in Puducherry between 01(st) August 2012 and 31(st) July 2015 were reviewed retrospectively from hospital case records as per the revised WHO guidelines for dengue fever. The diagnosis was confirmed by NS1antigen-based ELISA test or dengue serology for IgM and IgG antibodies and the data were analysed using SPSS 16.0 statistical software. After collecting all the data, all the variables were summarised by descriptive statistics. Categorical variables were expressed as frequencies and percentages, and then analysed by the chi(2) test or fishers exact test, where appropriate. Significance was taken at p value< 0.05. RESULTS: Among the 261 confirmed cases of dengue fever non-severe dengue and severe dengue infection was seen in 60.9% and 39.1% respectively. The mean age of presentation was 6.9 years and M:F ratio was 1.2:1. NS1 Ag was positive in 217 cases (83.1%) and among them non-severe dengue and severe dengue was seen in 65.9% and 34.1% cases respectively. A total of 44 cases (16.9%) were negative for NS1 Ag assay and positive for IgM MAC ELISA and among them 16 children (36.4%) had non-severe dengue infection where as 28 children (63.6%) had severe dengue infection. Secondary infection with (MAC-ELISA IgG) was seen in 17 cases (6.5%). NS1Ag assay was predominantly positive in acute phase sera, where as IgM/IgG MAC ELISA was predominantly positive in convalescent phase sera. There were six deaths (2.3%) and the common causes of poor outcome were multiorgan failure, encephalopathy and refractory shock. CONCLUSION: NS1 Ag assay is a useful early diagnostic marker for dengue fever but cannot be used as an early predictor of severe dengue infection. The criteria for admission in hospitals of cases of dengue fever should be based on clinical warning signs rather than positive NS1 Antigen test. PMID- 27190912 TI - Appearances are Deceptive - Passing a Nasogastric Tube does Not Always Rule Out Oesophageal Atresia. AB - Oesophageal atresia/trachea-Oesophageal fistula is commonly diagnosed in the newborn period by inability to pass a nasogastric tube (NGT). We present the instance of a newborn baby where the diagnosis of oesophageal atresia was delayed because of an apparent successful passage of nasogastric tube to the stomach. Failure to reinsert the NGT raised the suspicion of oesophageal atresia which was confirmed by contrast study showing blind upper oesophageal pouch. PMID- 27190913 TI - Role of Dynamic Contrast-Enhanced Magnetic Resonance Imaging in Staging of Bladder Cancer. AB - INTRODUCTION: Dynamic Contrast Enhanced (DCE)-Magnetic Resonance Imaging (MRI) is a useful technique in which rapid enhancement of tumour by uptake of the contrast agent compared to bladder wall. AIM: To evaluate the accuracy of dynamic gadolinium-enhanced MRI in staging of bladder cancer through differentiating superficial tumours from invasive tumours and organ-confined tumours from non organ-confined tumours. In addition, the benefits of DCE-MRI in diagnosis of tumour progression steps were investigated. MATERIALS AND METHODS: This was a quasi-experimental study in which 45 patients (95.55% men and 4.45% women) were enrolled. Patients with confirmed transitional cell carcinoma by histopathology findings were imaged using 1.5 Tesla MRI systems. Pathology results were considered as the standard reference. Tumour stage was determined by imaging findings and compared with pathologic findings after radical cystectomy. Data were analysed by SPSS version 16 and the level of significance in all tests was considered p<0.001. RESULTS: The most common stage that was seen in pathology and MRI findings was T3b. Kappa agreement coefficient between MRI and pathology was 0.7 (p<0.001). The accuracy of MRI in differentiating superficial tumours (<=T1) from invasive tumours (>= T2a), and organ-confined tumours (<=T2b) from non-organ confined tumours (>=T3b) was 0.97 and 0.84, respectively. The overall accuracy of MRI was 0.77 (p<0.001). Totally, 10 cases of disagreement between MRI and pathological staging were found, eight (80%) of which were overestimated and two cases (20%) underestimated. MRI detection rate was 0% in stage Ta, 100% in stage T1, 66.7% in stage T2, 86.7% in stage T3, and 100% in stage T4. The sensitivity and specificity of MRI in differentiating superficial tumours from invasive tumours were 0.97 and 1, respectively, and in differentiating organ-confined tumours from non-organ-confined tumours were 0.94 and 0.77, respectively. The Spearman's correlation coefficient between the signal enhancement slope of time intensity curves and tumour stages was 0.88 (p<0.001). CONCLUSION: Gadolinium enhanced MRI is an appropriate and useful modality with a high accuracy in determining the stage of the bladder cancer. In addition, this method shows extension and progression of tumour and tumour invasion depth. PMID- 27190915 TI - Thoracic Endometriosis-A Rare Cause of Haemoptysis. AB - Thoracic endometriosis is a rare condition and occurs in females of reproductive age due to the presence of active endometrial tissue in tracheobronchial tree, lung parenchyma and lung pleura. A typical history of haemoptysis during menstrual periods and strong suspicion of the disease entity is important for the diagnosis and management of the case. Diagnosis of the disease is usually delayed. Serial CT thorax during menstrual period and in non-menstrual period supports the diagnosis. We present here a case of catamenial haemoptysis. The diagnosis was missed initially but later a detailed clinical history revealed the same. Serial computed tomography of thorax taken during menstrual and after menstrual period supported the diagnosis. Though bronchoscopy was able to reveal hyperemic tissue in the tracheobronchial tree, bronchial washing was inconclusive. The patient was treated successfully with danazol. PMID- 27190914 TI - Study of Imaging Pattern in Bone Marrow Oedema in MRI in Recent Knee Injuries and its Correlation with Type of Knee Injury. AB - INTRODUCTION: The knee is a major weight bearing joint that provides mobility and stability during physical activity as well as balance while standing. If the knee is exposed to forces beyond its physiologic range, risk of injury to bone or soft tissue structures increases. A thorough understanding of knee injury patterns and their mechanisms may help in achieving more accurate assessment of injuries. AIM: To identify imaging pattern in bone marrow oedema and to correlate the pattern of bone marrow oedema retrospectively with type of knee injury from clinical history. MATERIALS AND METHODS: A cross-sectional study was done on all patients referred to Krishna Hospital, Karad for MRI knee with history of recent (< 6 weeks) knee injury. Study was conducted between May 2014 to September 2015 with a sample size of 200 patients. Plain radiograph of knee was done in all patients and they were scanned using 1.5 Tesla Seimens Avanto (Tim + Dot) with Tx/Rx 15 channel knee coil # Tim. RESULTS: Among the 200 cases, bone marrow contusion was noted in 138 cases (69%) and absent contusion in 62 cases (31%). Bone marrow contusion showed five patterns (according to Sanders classification) i.e., Clip injury in 39 cases (28.3%), Pivot shift injury in 78 cases (56.5%), Dashboard injury in eight cases (5.8%), Hyperextension injury in four cases (2.9%), Lateral patellar dislocation in three cases (2.2%). In six cases (4.3%) no pattern of bone marrow contusion could be explained and was categorized as unclassified pattern. CONCLUSION: Pivot shift pattern is most common contusion pattern and the most common type/mode of sports related injury. By analysing bone marrow contusion pattern, type/mode can be determined in most of the cases. By applying a biomechanical approach in MR interpretation, it is possible to detect lesions like ligament rupture and osseous contusion, to predict subtle but it might overlook important abnormalities. PMID- 27190916 TI - Congenital Absence of Internal Carotid Artery with Rare Type of Intercavernous Anastamosis and Ruptured Cerebral Aneurysm. AB - Congenital absence of Internal Carotid Artery (ICA) is a rare anomaly seen in <0.01% of the population. Various collateral circulations develop in these cases to maintain adequate cerebral perfusion. High incidence of aneurysms is reported in these cases. Complete evaluation is required to detect other abnormalities usually seen in these patients. We report a case of congenital absence of right ICA in a 39-year-old female who presented with Subarachnoid Haemorrhage (SAH) and had a Middle Cerebral Artery Aneurysm (MCA). The right MCA got supply from the intercavernous communication from the left internal carotid artery. Skull base Computed Tomogram (CT) confirmed the congenital absence of right ICA. She underwent successful surgical clipping for the aneurysm. The high incidence of aneurysms, collateral circulations, embryological development and postulated mechanisms of this anomaly were discussed. The exact aetiology behind the absence of ICA remains unclear. It is important to differentiate this condition from acquired stenosis/occlusion due to atherosclerosis and carotid dissection. Recognising the anomaly is important and gains even more significance during surgical planning in cases of direct aneurysm clipping, carotid endarterectomy and transphenoidal surgeries. PMID- 27190917 TI - Male Breast Abscess Secondary to Actinomycosis: A Case Report. AB - Primary breast actinomycosis is a rare condition that has been previously reported in the female breast. Male breast infection is uncommon and most often associated with trauma to the skin or predisposing conditions like diabetes. We report the first case to our knowledge of primary breast actinomycosis in the male breast caused by Actinomycesneuii (A. neuii), a rare strain of Actinomyces. Mammography demonstrated periareolar skin thickening with a mottled pattern. Sonography showed multiple small cystic structures. Definitive diagnosis was made by culture of the nipple discharge. PMID- 27190918 TI - Ruptured, Intracranial Dermoid Cyst - A Visual Diagnosis? AB - Dermoid cysts are a very rare entity of intracranial tumours. The traumatic or non-traumatic rupture of the cyst wall is a serious complication that can be treated surgically or conservatively depending on the clinical symptoms. However, more common entities have to be considered as a differential diagnosis. We report on a female patient who was admitted with complaints of significant, prolonged headache and diffuse pain. Analysis of her blood and cerebrospinal fluid indicated no clear pathology. A CT examination of the head revealed a ruptured dermoid cyst adjacent to the left sphenoidal bone. An additional MRI was conducted to confirm the CT findings and rule out an intracranial ischemia or vasospasms. A conservative therapy was scheduled and the patient recovered well. Using current imaging techniques, especially magnetic resonance imaging, it is possible to identify a ruptured dermoid cyst by its pathognomonic signal behavior and rule out potentially life threatening complications. PMID- 27190919 TI - Pulmonary Aspergillosis: What CT can Offer Before it is too Late! AB - Aspergillus is a large genus of saprophytic fungi which are present everywhere in the environment. However, in persons with underlying weakened immune response this innocent bystander can cause fatal illness if timely diagnosis and management is not done. Chest infection is the most common infection caused by Aspergillus in human beings. Radiological investigations particularly Computed Tomography (CT) provides the easiest, rapid and decision making information where tissue diagnosis and culture may be difficult and time-consuming. This article explores the crucial role of CT and offers a bird's eye view of all the radiological patterns encountered in pulmonary aspergillosis viewed in the context of the immune derangement associated with it. PMID- 27190921 TI - Comparative Efficacy of Intrathecal Bupivacaine Alone and Combination of Bupivacaine with Clonidine in Spinal Anaesthesia. AB - INTRODUCTION: Clonidine is an alpha2 agonist agent that has been used as an adjuvant to local anaesthetics in regional anaesthesia. AIM: This study compared two combinations of bupivacaine and clonidine with bupivacaine alone for surgeries below the level of umbilicus in spinal anaesthesia. MATERIALS AND METHODS: We conducted a randomized double blind study on 90 patients of ASA I and ASA II aged 20-60 years, 30 in each group, undergoing surgery below the level of umbilicus in spinal anaesthesia. For intrathecal block, Group 1 received bupivacaine hydrochloride 12.5mg (2.5ml) in 8% dextrose (0.5% sensorcaine heavy) + 1ml (150MUg) of preservative free clonidine. Group 2 received bupivacaine hydrochloride 12.5mg (2.5ml) in dextrose (0.5% sensorcaine heavy) + 0.5ml (75MUg) of preservative free clonidine + 0.5ml of normal saline to make the volumes of all the groups same. Group 3 received bupivacaine hydrochloride 2.5ml in 8% dextrose (0.5% sensorcaine heavy) + 1ml of normal saline to make the volumes of all the groups same. Heart rate, NIBP, oxygen saturation and respiratory rate were monitored. The onset and duration of sensory block, the highest dermatomal level of sensory block, motor block, time to complete motor block recovery and duration of spinal anaesthesia were recorded. STATISTICAL ANALYSIS: The data of the study was recorded in the record chart and results were evaluated using statistical tests (ANOVA test, post-hoc turkey hsd test, paired t-test and chi square test). RESULTS: Demographic data, the incidence and duration of bradycardia were comparable amongst the groups. The duration of sensory and motor block were greatest in group 1, followed by group 2 and group 3 (p <0.01). Decrease in the systolic blood pressure of group 2 and group 3 was noted as compared to group 1. No significant sedation or respiratory depression was observed in any group. CONCLUSION: Addition of clonidine to bupivacaine intrathecally is although a reliable method to prolong spinal anaesthesia but close monitoring for hypotension is desirable. PMID- 27190920 TI - Hot Climate and Perioperative Outcome in Trauma Patients. AB - INTRODUCTION: Extreme hot climatic conditions constitute a major public health threat. Recent studies have shown higher rate of perioperative complications during hot weather. Although a lot of researches have been carried out to evaluate effect of hot climatic conditions and its correlation with other medical conditions, but very little has been studied in trauma patients. AIM: To evaluate the impact of hot climatic conditions on perioperative morbidity in trauma patients. MATERIALS AND METHODS: We enrolled 100 trauma patients scheduled for surgery after approval by the Hospital and University Ethical Committee. Patients were grouped as Control Group (C) when outdoor temperature ranged in comfortable zone i.e., 20-29(0)C and Study Group (S) when outdoor temperature ranged 40(0)C or more. Patients living in regular air conditioned atmosphere (more than 18 hours per day) and with co-morbid conditions or on drugs interfering with temperature regulation were excluded. Student's t-test, z-test and chi-square tests were used for statistical analysis. RESULTS: Both groups were comparable in terms of demographics, age (control group C=38.2+/-12.93 years and in group S= 40.14 +/- 15.98 years), sex, socioeconomic status and type of surgery. Mean Trauma Index Score (TIS) were 6.20+/-1.56 and 5.80+/-1.31 respectively. All patients were of low risk as per Shoe Maker's risk criteria. Post Anaesthesia Care Unit (PACU) stay was similar. Mean duration of hospital stay was 12.16 +/- 8.50 days in group C and 10.98 +/- 6.90 days in group S (p-value 0.21). 20% patients in group C whereas 54% in group S had complications (p= 0.009). There was a higher incidence of infections as well as respiratory distress in group S. On multiple logistic regression analysis peak environmental temperature was found to be the single independent risk factor for predicting perioperative morbidity. CONCLUSION: High ambient temperature adversely affects the outcome of surgery even in low risk young trauma patients belonging to American Society of Anaesthesia (ASA) physical status I and II categories. So we opine that it may be probably helpful to either postpone non-emergency surgery till fair adaptation is achieved in air conditioned environment of hospital or be cautious for complications to reduce the heat related perioperative morbidity in days of heat waves. PMID- 27190922 TI - Optimal Dose of Intrathecal Dexmedetomidine in Lower Abdominal Surgeries in Average Indian Adult. AB - BACKGROUND: Dexmedetomidine, a selective alpha2 adrenoceptor agonist, has been used as adjuvant to spinal anaesthesia. AIM: To find out the optimum dose of dexmedetomidine to be used in lower abdomen surgery intrathecally. MATERIALS AND METHODS: This was a randomized, controlled, double blinded study which included adult ASA I and II patients. They were allocated into five groups (n=20). Patients allergic to drugs to be used in the study and those with co-existing neurological disorders, coagulopathies, cardiac diseases, obesity and hypertension were excluded. Groups were designed as 2.5ml hyperbaric bupivacaine with 0.5ml saline (Control) or 0.5ml dexmedetomidine: 5mcg (D1), 10mcg (D2), 15 mcg (D3) and 20mcg (D4). Data were collected for 10 point VRS for pain, Bromage motor block, Ramsay sedation score, haemodynamics, time of first rescue analgesia (TRA) and any adverse effects and groups were analysed using one way analysis of variance (ANOVA) by SPSS16.0 (p-value <0.05 significant). RESULTS: The mean duration of analgesia and need of first rescue analgesics are 201.5+/-29.1 mins in control group but in D1 group 259.1+/-15.2 mins, D2 310.7+/-48.1mins, D3 540.3+/-51.6 mins and D4 702.4+/-52 mins. p=0.003. The mean highest VRS score along with analgesic requirements were significantly reduced in dexemeditomidine groups, but D3 and D4 had hypotension which needed correction. CONCLUSION: Weighing the prolongation of anesthesia and analgesia and side effects we conclude that 10 mcg of dexmedetomidine is optimum intrathecal dose. PMID- 27190923 TI - Optimum Concentration of Caudal Ropivacaine & Clonidine - A Satisfactory Analgesic Solution for Paediatric Infraumbilical Surgery Pain. AB - INTRODUCTION: Ropivacaine is amide local anaesthetic pure S(-)enantiomer of bupivacaine. Its duration of analgesia is similar to that of Bupivacaine (in equivalent doses) but the motor block is slower in onset, less intense, shorter in duration for a given level of sensory block with lesser cardiac side effects but addition of an adjuvant like clonidine which is an imidazoline derivative has been studied for its sedative, anxiolytic and analgesic properties. AIM: This study was aimed to show the optimum concentrations of Ropivacaine and Clonidine to maximize analgesia without side effects by evaluating its safety and efficacy. MATERIALS AND METHODS: Sixty children aged 2-10 years of ASA grade 1, scheduled to undergo infraumbilical surgeries were randomly allocated to Group A & Group B of 30 each. Group A received 0.2% Ropivacaine with normal saline and Group B received 0.2% Ropivacaine and preservative free Clonidine 1MUg/kg, the total volume of solution being 1ml/kg haemodynamic changes were monitored intraoperatively and haemodynamic parameters along with motor blockade, pain score and sedation score were assessed postoperatively. STATISTICAL ANALYSIS: Done with unpaired student t and Mann-Whitney test. RESULTS: The groups were comparable regarding demographic characterstics. The mean duration of analgesia was prolonged in group B (12+2.22 hours) than in group A (6.53+1.16 hours) with p value <0.001 leading to less rescue analgesia in former group. None of the children in the groups had a pain score of >= 4 at the end of 2 hours. A 6.6% and 60% of group A children had score of >= 4 at the end of 4(th) & 6(th) hour respectively. None in Group B had a score of >= 4. At the end of 8(th) hour, only 6.6% of the children in Group B had a pain score of >= 4 whereas it was 33.33% in Group A which is statistically significant. No bradycardia or hypotension and no significant sedation. CONCLUSION: Combination of Ropivacaine and Clonidine in the concentration used (0.2% ropivacaine and 1MUg/kg of clonidine) can be optimal for postoperative analgesia in paediatric population. PMID- 27190924 TI - Efficacy of Magnesium Sulphate as an Adjunct to Ropivacaine in Local Infiltration for Postoperative Pain Following Lower Segment Caesarean Section. AB - INTRODUCTION: Intravenous and peri-articular magnesium has been shown to reduce perioperative analgesic consumption. With this background, subcutaneous infiltration was hypothesized to potentiate the subcutaneous infiltration of local anaesthetic agent. AIM: To comparatively evaluate the efficacy of magnesium sulphate as an adjunct to ropivacaine in local infiltration for postoperative pain following lower segment cesarean section. MATERIALS AND METHODS: Sixty parturients undergoing cesarean delivery were randomized to either group A or B in a double blinded manner. After uterine and muscle closure but before skin closure, Group A was administered local subcutaneous wound infiltration of Injection (Inj) ropivacaine 0.75% 150 milligram (mg) or 20 millilitres(ml) whereas, group B patients were given a local subcutaneous wound infiltration of Inj magnesium sulphate 750 mg (1.5 ml of Inj 50% Magnesium sulphate) added to Inj ropivacaine 0.75% (18.5 ml) making a total volume of 20 ml. In postoperative period, Heart rate (HR), Mean Arterial Pressure (MAP), Visual Analogue Score (VAS), supplemental analgesic consumption and timing of each subsequent analgesic was noted for the initial 24 hours. RESULTS: There was no difference in the timings for the requirement of first Intravenous (IV) rescue analgesic among both the groups (p=0.279). However, the need for 2(nd) and 3(rd) doses of rescue analgesics was significantly later in group B and the difference was statistically significant with p-value of 0.034 and 0.031 respectively. The number of patients who were administered 2(nd), 3(rd) and 4(th) doses of rescue analgesics was significantly greater in group A as compared to group B. None of the patients in group B needed more than 4 doses of rescue analgesia while in group A, 5 patients were administered a rescue analgesic for 5(th) time. The cumulative analgesic requirement in the initial 24 hours was also greater in group A as compared to group B and the difference was statistically significant (p =0.01). The incidence of adverse effects was similar in both the groups. CONCLUSION: Subcutaneous infiltration of magnesium along with local anaesthetic prolongs the analgesic efficacy of local anaesthetic and is not associated with any significant adverse effects. PMID- 27190925 TI - Innovative Application of a Microlaryngeal Surgery Tube for difficult Airway Management in a Case of Down's Syndrome. AB - An 11-year-old male child, known case of down's syndrome with congenital oesophageal stricture was posted for oesophageal dilatation. Preoperative airway assessment revealed a high arched palate, receding mandible and Mallampati Score of 2. During surgery, after loss of consciousness which was described as loss of eyelash reflex and adequate jaw relaxation, direct laryngoscopy and endotracheal intubation was attempted with a cuffed endotracheal tube number 5.0mm ID (internal diameter). The endotracheal tube could not be negotiated smoothly, so 5.0mm ID uncuffed endotracheal tube was used which passed through easily, but on auscultation revealed a significant leak. Later, intubation via a Micro Laryngeal Surgery (MLS) cuffed tube 4.0mm ID was attempted. The MLS tube advanced smoothly and there was no associated leak on positive pressure ventilation. Thus by innovative thinking and avant-garde reasoning, a definitive airway device could be positioned with no other suitable alternative at hand. PMID- 27190926 TI - The Efficacy of Three Learning Methods Collaborative, Context-Based Learning and Traditional, on Learning, Attitude and Behaviour of Undergraduate Nursing Students: Integrating Theory and Practice. AB - INTRODUCTION: Communication skills training, responsibility, respect, and self awareness are important indexes of changing learning behaviours in modern approaches. AIM: The aim of this study was to investigate the efficacy of three learning approaches, collaborative, context-based learning (CBL), and traditional, on learning, attitude, and behaviour of undergraduate nursing students. MATERIALS AND METHODS: This study was a clinical trial with pretest and post-test of control group. The participants were senior nursing students. The samples were randomly assigned to three groups; CBL, collaborative, and traditional. To gather data a standard questionnaire of students' behaviour and attitude was administered prior to and after the intervention. Also, the rate of learning was investigated by a researcher-developed questionnaire prior to and after the intervention in the three groups. RESULTS: In CBL and collaborative training groups, the mean score of behaviour and attitude increased after the intervention. But no significant association was obtained between the mean scores of behaviour and attitude prior to and after the intervention in the traditional group. However, the mean learning score increased significantly in the CBL, collaborative, and traditional groups after the study in comparison to before the study. CONCLUSION: Both CBL and collaborative approaches were useful in terms of increased respect, self-awareness, self-evaluation, communication skills and responsibility as well as increased motivation and learning score in comparison to traditional method. PMID- 27190928 TI - Behavioural Variant Frontotemporal Dementia with Bilateral Insular Hypometabolism: A Case Report. AB - Fronto-Temporal Dementia (FTD) is a cluster of syndromes, characterized by progressive deterioration of cognition, language and/or behavioural changes associated with degeneration of the frontal and temporal lobes. A 53-year-old man was admitted with a history of gradually progressive behavioural disturbances, disinhibition, unprovoked anger outbursts, apathy, disorganised behaviour and impaired self-care. A clinical diagnosis of Fronto temporal Dementia (behavioural variant) was made. Extensive investigations found no abnormality except in FDG PET scan of the brain which revealed hypo metabolism in bilateral anterior insular region. Insula is an important brain area implicated in emotional awareness and behaviour control. Hypo metabolism in insular region in the absence of any structural neuroimaging findings, in a case of behavioural variant of Fronto-temporal dementia suggest that, it might be one of the earliest neurobiological changes occurring in this disorder. PMID- 27190927 TI - Study of Life Events and Personality Dimensions in Generalized Anxiety Disorder. AB - INTRODUCTION: Life events, recognized as stressors, due to their unanticipated nature, can cause psychiatric illness. Also there is some line of continuity between neurotic illness and antecedent personality traits. AIM: To study generalized anxiety disorder in relation to Life events and personality dimensions. MATERIALS AND METHODS: Certain hypotheses were tested in two groups, namely 30 Generalized Anxiety Disorder patients (GAD) and 30 matched controls, by utilizing assessment tools. These include: GAD patients experience more undesirable Life events than normal; GAD patients with high level of anxiety experience more undesirable Life events; Neuroticism is related to the severity of anxiety; Extroverts experience more anxiety; Level of anxiety in females is higher; GAD patients with higher education level experience more anxiety, while those with lower education level somatize more. The group differences were examined using Chi-Square test, Student t-test and ANOVA. Pearson's Correlation Co-efficient was used to find the correlation between anxiety and the undesirable Life events. The level of statistical significance was set at p<0.05. RESULTS: GAD patients experienced significantly more undesirable Life events than the matched controls. Patients with high level of anxiety experienced more undesirable Life events, with the coefficient of correlation being quite high. A significant association between Neuroticism scale and GAD was observed. CONCLUSION: The study suggests a possible causative link between the undesirable Life events and GAD; and a significant association between Neuroticism dimension and the anxiety disorder. Role of environmental stressors and personality traits in treatment outcome among GAD patients awaits further, prospective studies. PMID- 27190929 TI - A Rare Case of Mayer-Rokitansky-Kuster-Hauser Syndrome Presenting with Acute Psychosis. AB - The psychiatric co-morbidities in female population with mullerian agenesis is an area with limited research. This is probably due to the fact that when those patients are diagnosed not much attention or information is given for long term psychiatric follow-up. Owing to their inability to bear children, these subjects often become socially harassed. Thus these constant stressors may lead to development of psychopathology in future. Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is a congenital abnormality with absence of uterus, cervix and vagina, but normal secondary sexual characteristics and external genitalia and occurs in every 1 out of 4000-10,000 females. There is also limited literature on the probable common chromosomal aetiology for both psychosis and MRKH patients. We, present here a case of MRKH syndrome, whose initial presentation was psychosis only. In this respect, we also highlight the much neglected need of appropriate psychiatric screening and provision of psychiatric care in this population. PMID- 27190930 TI - Mobile Phone Dependence among Adolescents; Can We Utilize Mobile Phone as a Therapeutic Approach? PMID- 27190931 TI - The Arid Melancholy-Netherton Syndrome With Protein Energy Malnutrition. AB - Netherton Syndrome (NS) is a rare autosomal recessive hereditary ichthyosiform disease with a classical triad comprising of an ichthyosiform dermatosis, hair shaft abnormalities and atopic diathesis. There is a mutation in a gene named Serine Protease Inhibitor Kazal type-5 (SPINK5); a new type of serine protease inhibitor involved in the regulation of skin barrier formation and immunity. Skin manifestations include, Ichthyosis Linearis Circumflexa (ILC), polycyclic and serpiginous, erythematous plaques with characteristic migratory, double-edged scale at the margins, or Congenital Ichthyosiform Erythroderma (CIE). Most of the patients have elevated immunoglobulin class E (IgE) and show atopic manifestations. Hair shaft abnormalities like pili torti and/or trichorrhexis nodosa, trichorrhexis invaginata, are seen. Here, we report a rare case of Netherton Syndrome having ILC and trichorrhexis nodosa with protein energy malnutrition in a five-year-old school going girl. She belonged to a poor socio economic background and was worried about her physical appearance due to her skin lesions, causing psychosocial morbidity to her. PMID- 27190932 TI - Anogenital Pruritus - An Overview. AB - Anogenital pruritus is defined as intense itching, acute or chronic, affecting the anal, perianal, perineal and genital skin, which is a dominant problem in the course of various cutaneous and systemic conditions. It is one of the common, extremely annoying symptom for which patients attend the Dermatology Outpatient Department (OPD). Anogenital skin is highly sensitive to soaps, perfumes, clothing and superficial trauma and it is more prone for itchy dermatoses as a result of warmth, friction, lack of aeration, sweating and occlusive inner garments. Anogenital pruritus is associated with a wide spectrum of diseases which includes localized infections, infestations, inflammatory dermatoses, allergic and irritant conditions, anorectal diseases, systemic causes, nutritional disorders, psychological and when the cause cannot be found out it is often termed idiopathic. Patients are highly reluctant in consulting the physician for anogenital itch in the early stage, they usually present at a later stage with either atypical manifestations or depigmentation and lichenification, secondary to constant scratching. They often resort to over the counter topical agents, particularly combination products which contain topical steroids. The irrational use of such products results in complications like skin atrophy, striae, incognito etc. A proper clinical history, clinical examination, investigations like scrapping for fungus and itch mite, skin biopsy, patch test and relevant blood investigations to rule out systemic conditions should be carried out, when needed, to arrive at an accurate diagnosis, before treating the patient. PMID- 27190934 TI - Primary Inverted Papilloma of Middle Ear and Mastoid: A Rare Case Report. AB - Inverted papilloma or Schneiderian papilloma arising primarily from middle ear and mastoid is a very rare entity. It is a benign and locally aggressive condition, with increased risk of recurrence and malignant transformation. Surgery is the primary treatment. Radiation therapy should be considered in case of malignant transformation, recurrent or inoperable disease. Here we are reporting a case of recurrent inverted papilloma with dysplastic changes arising from mastoid cavity in a 60-year-old male. The patient was treated with surgery followed by radiotherapy. PMID- 27190933 TI - Antiproliferative and Apoptotic Effect of Curcumin and TRAIL (TNF Related Apoptosis inducing Ligand) in Chronic Myeloid Leukaemic Cells. AB - INTRODUCTION: Curcumin, traditionally utilized as a flavouring zest as a part of Indian cooking, has been accounted to decrease the proliferation potential of most cancer cells. Apoptosis is a mechanism by which most anticancer therapies including chemotherapy, radiation and antihormonal therapy kill tumour/cancer cells. Novel agents that may sensitize drug-resistant tumour cells for induction of apoptosis by customary treatments could lead to the regression and improved prognosis of the refractory disease. Indeed, chemotherapeutic agents have been shown to sensitize cancer cells to killing by death ligands such as tumour necrosis factor-alpha. AIM: To investigate cytotoxicity and apoptotic effect of curcumin in chronic myeloid leukaemic cell line KCL-22. MATERIALS AND METHODS: In present study, different doses of curcumin (10,25,50,75,100MUM) and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) (25,50 MUM) alone and combine regimen were exposed to myeloid leukaemic cell KCL-22. The cell viability was monitored by MTT assay, apoptotic activity by binding of Annexin V-FITC using fluorescence microscopy and cell cycle check points by flow cytometry. RESULTS: Cytotoxic assay revealed that curcumin and TRAIL induced both dose and time dependent decrease in cell viability. Significant cell cytotoxicity was seen in combine regimen of both curcumin and TRAIL at 48 h of exposure. Cells treated with curcumin and TRAIL was arrested at the S phase, as revealed by flow cytometric analysis. Subtoxic concentrations of the curcumin-TRAIL combination induced strong apoptotic response in KCL-22 cells as demonstrated by the binding of Annexin V-FITC. CONCLUSION: Our study conclude that curcumin inhibits the cancer cell growth by inducing apoptosis and enhance the therapeutic potential of TRAIL which recommends that both curcumin alone or in combination with TRAIL might be useful for leukaemic prevention and better therapeutic responses. PMID- 27190936 TI - Follicular Variant of Papillary Carcinoma Arising in Struma Ovarii. PMID- 27190935 TI - Massive Intrabile Duct Invasion Caused by a Fatal Progression of Colonic Adenocarcinoma: Abdominal Computed Tomography Findings and Cholangiography Correlation. AB - In this report, we present an unusual case of jaundice in a patient with advanced colorectal cancer due to intraductal tumour invasion of the intra- and extrahepatic biliary tree. This complication proved to be fatal despite aggressive therapeutic management. A correct diagnosis of this type of involvement was achieved by a combination of diagnostic and therapeutic cholangiography. Despite adequate biliary decompression, the patient died from liver failure and biliary sepsis. PMID- 27190937 TI - Atypical Lymphocytes and Cellular Cannibalism: A Phenomenon, First of its Kind to be Discovered in Chronic Periapical Lesions. AB - INTRODUCTION: Lymphocytes are often termed to be isomorphic, having a monotonous light microscopic appearance. Morphological aspects of lymphocytes in tissue sections thereby are not routinely taken notice of as their morphology seems to vary only in case of lymphoid malignancies, hematological malignancies apart from certain viral infections. Atypical lymphocytes are the lymphocytes with unusual shape, size or overall structure. These are more commonly known as reactive lymphocytes. The unusual histomorphological feature of these cells include larger size than normal lymphocytes; in some cells the size exceeds even 30 microns. The large size is the result of antigenic stimulation of the cell. Alongwith these, the other rare feature which is recently coming under light is "Cellular Cannibalism" which is defined as a large cell enclosing a slightly smaller one within its cytoplasm. Previously, this feature was noted only in cases of malignant tumors. AIM: The objectives of this study were to determine the proportion of atypical lymphocytes in chronic periapical granulomas and cysts; to determine the proportionate cellular cannibalism in these periapical lesions. MATERIALS AND METHODS: This was a descriptive, observational study conducted in the Department of Oral Medicine and Radiology and Oral Pathology and Microbiology. Haematoxylin and eosin stained 30 slides of chronic periapical granulomas and 20 slides of cysts reported in the year 2014-15 and the clinical proformas of the patients were retrieved from the files of the Department of Oral Medicine and Radiology and Oral Pathology and Microbiology. These slides were evaluated by 3 experts from the specialization of Oral Pathology and Microbiology to determine the presence of atypical lymphocytes and cellular cannibalism under high power magnification (400X). RESULTS: Out of the 30 slides of chronic periapical granulomas, about 12 slides (40%) revealed presence of atypical lymphocytes. In case of slides of chronic periapical cysts, however, only 4 out of the 20 slides (20%) examined histopathologically showed presence of atypical lymphocytes. An interesting feature of cellular cannibalism was noted in tissues with atypical cells. Cannibalistic cells were present in 12 out of the 30 slides of chronic periapical granulomas (40%). None of the cysts, however, revealed cannibalistic cells (0%). CONCLUSION: In the present study, we have quoted our observations on the unique cellular composition that was seen in histopathological sections of chronic periapical lesions. As also it was noted that those cases in which atypical cells & cellular cannibalism was evident the lesion clinically showed size more than 5cm. The question arises that whether presence of atypical cells from the tissue sections in these lesions denotes an aggressive clinical behavior and should be given a due consideration in deciding the treatment protocols for such cases to provide an optimum patient care. PMID- 27190938 TI - A Clinical Study to Examine the Effect of Complete Denture on Head Posture/Craniovertical Angle. AB - INTRODUCTION: Edentulous patients show some significant changes in ridge relationship caused by resorption of alveolar ridge. The changes are characterized by an upward rotation of mandible, increase in mandibular prognathism that ultimately results in change of natural head posture. AIM: This clinical study was planned to know the effect of complete denture on head posture in different age groups of Indian completely edentulous population, after placement of complete denture at various time intervals. MATERIALS AND METHODS: The sample consisted of completely edentulous patients without previous experience of the dentures. They were divided into 2 age groups: Group A (45-60) and Group B (61-75). During placement of complete denture craniovertical angle was measured with the help of custom made ruler protector device. Readings were taken before denture placement, immediately after denture placement, 30 minutes, 24 hours and 30 days after dentures placement. RESULTS: The results of this study indicated that in most of the patients (90%) despite their age, change in head posture (extension) occurred immediately after the denture placement. Thereafter reading remains same for measurement at 30 minutes and 24 hours of denture placement. However after 30 days, observation revealed that all the patients showed reduced craniovertical angle (flexion). Even though the values of craniovertical angle remain higher than its baseline in both groups, significant changes were noticed only in Group A. CONCLUSION: Findings revealed that head posture was significantly altered by the placement of dentures in completely edentulous patients. Within the time interval of 30 minutes and 24 hours extension of head posture remained constant with slight variation. Although after 30 days, changes remained significant for group 'A', but no significant changes were observed in the subjects of group 'B'. PMID- 27190939 TI - Prevalence of Dental Caries among School Children in Chennai, Based on ICDAS II. AB - INTRODUCTION: Dental caries is a common dental disease, which occurs during childhood and continues to be a major public health problem. The prevalence of dental caries was associated with oral hygiene practice, sugar consumption and implementation of the preventive oral health program. AIM: The purpose of this study was to assess the prevalence of dental caries in school children aged between 6-14 years using the International Caries Detection and Assessment System (ICDAS II). MATERIALS AND METHODS: The study population consisted of 2796 school children living in Pallikkaranai, Chennai, India and studying in government recognized schools. Each student was examined by a single examiner using ICDAS system under natural light during normal school hours. RESULTS: The prevalence of dental caries was 68.8% in the total surveyed population. The gender-wise prevalence of dental caries shows, females to have slightly higher prevalence than male. The prevalence of dental caries at the age group of 6 years was 57%, seven year 67%, eight year 63%, nine year 74%, 10 year 76%, 11 year 74%, 12 year 69%, 13 year 71%, and 14 year 69%. The distribution of CARS (Caries associated with Sealants and Restorations) in the surveyed population was only 1.4. CONCLUSION: The distribution of non-cavitated/early enamel lesions was higher in the studied population and indicated a requirement of a sustained dental health preventive program targeting specific segments of the population. PMID- 27190940 TI - Time Dependent Effect of a Denture Cleanser on the Sorption and Solubility of Four Soft Liners-An Invitro Study. AB - INTRODUCTION: Soft liner materials, when used with ill fitting dentures, are constantly kept in a wet environment of either saliva or denture cleanser that affects their sorption and solubility. These inturn have detrimental effect on other properties. AIM: To evaluate the influence of different exposure times of a commonly used denture cleanser on sorption and solubility of four soft liners. MATERIALS AND METHODS: Metal disc was fabricated to make the mould space for soft liner samples. Four materials were used, long term and short term acrylic liners; long term and short term silicone liners. Each of these were divided into four groups: first control group- all liners were kept in artificial saliva for entire period of study. Second group- liners were immersed daily in cleanser for 1 hour and then transferred to artificial saliva for rest of the day. Similarly samples of third and fourth groups were immersed in cleanser for 4 and 8 hours respectively and transferred to artificial saliva. Sorption and solubility tests were conducted and statistical analysis done. STATISTICAL ANALYSIS: One-way ANOVA followed by Post-hoc Tukey's test for pair wise comparisons was done. Significance was set at the probability level of p < 0.05. RESULTS: Solubility values of all groups were higher than the quoted ADA specifications. CONCLUSION: Overall, silicones performed better than acrylics. Long term silicone was most stable. Short term acrylic was most unstable. The 8 hour immersion in denture cleanser caused significantly high sorption and solubility. PMID- 27190941 TI - To Evaluate the Efficacy of an Innovative Irrigant on Smear Layer Removal - SEM Analysis. AB - INTRODUCTION: The goal of endodontic therapy is to completely eliminate the microorganisms and the smear layer from the root canal in order to provide a good seal of the root filling materials. AIM: The aim of this study was to find a viable alternative irrigant, which is easily available with less erosion and clinically acceptable smear layer removal by comparing the efficacy of EDTA and commercially available super-oxidized water, named Oxum, as a final rinse on smear layer removal and erosion in relation to coronal, middle and apical thirds of radicular dentin using Scanning Electron Microscope (SEM) analysis. MATERIALS AND METHODS: Freshly extracted 30 human lower second premolar teeth with straight roots and type I canal anatomy were selected. The root canals were cleaned and shaped using Universal Protaper Rotary System. Irrigation was performed with 1 ml of 2.5% of NaOCl solution after each instrument change. The final irrigation (5 ml) sequence was as follows: Group I- 17% EDTA, Group II - OXUM, and Group III - 0.9% saline (control) for one minute. Then, the root canals were finally irrigated with 5ml of distilled water to remove any precipitate. The roots were then gently split into two halves using a chisel and subjected to SEM analysis. RESULTS: The SEM photomicrographs were evaluated by two independent examiners and Mann Whitney results showed that there was no statistically significant difference between the two examiners. Non-parametric statistical analysis of all experimental groups showed significant difference between coronal, middle and apical third for smear layer removal with p-value<0.05. For erosion, in group II (oxum) showed statistically significant difference between coronal, middle and apical third and it showed significantly less dentine erosion when compared to EDTA. CONCLUSION: Within the limitations of the present study, Oxum the commercially available super-oxidized water proved to be equally effective in smear layer removal with less erosion when compared to EDTA. PMID- 27190942 TI - Prevalence and Characteristic of Headache in Dental Professionals: A Questionnaire Based Survey. AB - INTRODUCTION: Medical and dental streams in today's date are considered highly demanding and stressful educational environments. Dental professionals, students and faculty, encounter great deal of stress in form of academic stress and job performance. Headache is a major and common neurological problem and is the main reason for decreased work performance, absenteeism and behavioral disturbances in dental professionals. AIM: In current scenario of increasing stressful conditions in dental professionals, the present study was carried out with an aim to assess the prevalence and characteristic of headache in dental professionals in Udaipur, India. MATERIALS AND METHODS: A cross-sectional questionnaire based study was conducted in a private dental teaching hospital in Udaipur. The undergraduate, postgraduate dental students and faculty members, who gave consent, were included in the study. Information regarding the reason for headache and its various parameters was collected. Statistical analysis was done using SPSS version 22 and descriptive statistics was used to compare the results obtained. RESULTS: The headache was found to be prevalent in 87.1% of the subjects included in the study. Females (91.9%) were more frequently affected by headaches than males (87.1%). CONCLUSION: It can be concluded from the present study that headache was the main cause of absenteeism at school and work, mood and behavioral changes and inappropriate work actions. PMID- 27190943 TI - Effect of ACP-CPP Chewing Gum and Natural Chewable Products on Plaque pH, Calcium and Phosphate Concentration. AB - INTRODUCTION: Numerous epidemiological studies have documented dental caries as the major public health problems throughout the world. It is gradually increasing in the underdeveloped and developing countries especially in children due to increasing popularity of refined sugars. AIM: The aim of the study was to evaluate the effect of natural chewable products (Tulsi, sesame seeds, fennel seeds, coconut) and ACP-CPP chewing gum on plaque pH, calcium and phosphate concentration. MATERIALS AND METHODS: A randomized controlled trial, with a cross over study design, was conducted. Ten subjects aged 15-17 years who agreed to refrain from oral hygiene practice for 48 hours prior to the sample collection were selected for the study. The baseline plaque pH, calcium and phosphate was measured and repeated after 5 and 30 minutes. It was ensured that each study participant was subjected to all the products making an effective sample of ten subjects per product. The data was statistically analysed. RESULTS: The mean pH in all the study groups increased after 5 minutes and 30 minutes compared to baseline, except for coconut group at 30 minutes and fennel group at 5 minutes. Highest increase in plaque calcium concentration was found in fennel group followed by recaldent and sesame, respectively. Whereas, the highest increase in plaque phosphate was found in recaldent group followed by sesame group and fennel group respectively. CONCLUSION: Plant products can be effective, inexpensive, easily accessible methods of maintaining oral health. Further studies are recommended to confirm long term effects. PMID- 27190944 TI - Friction between Archwire of Different Sizes, Cross Section, Alloy and Brackets Ligated with Different Brands of Low Friction Elastic Ligatures- An Invitro Study. AB - INTRODUCTION: Friction in orthodontic treatment does exist and is thought to reduce the efficiency of orthodontic appliances during sliding mechanics. During sliding mechanics, a friction force is produced at the bracket archwire-ligature unit which tends to counteract the applied force and in turn resists the desired movement. AIM: The aim of this invitro study was to determine the friction between archwire of different sizes, cross section, alloy and brackets ligated with different brands of low friction elastic ligatures. MATERIALS AND METHODS: An 0.022-in slot, 10 stainless steel brackets and various orthodontic archwires which were ligated with low-friction ligatures and subjected to evaluate frictional resistance i.e. static friction and dynamic friction. The archwires of 0.014" and 0.016" nickel titanium (NiTi), 0.016 * 0.022" stainless steel (SS), 0.017 * 0.025" NiTi, 0.017 * 0.025" SS, 0.017 * 0.025" titanium molybdenum alloy (TMA), 0.019 * 0.025" SS were used. Each bracket/archwire combination was evaluated 10 times at room temperature of 27 +/- 2 degrees C. The study groups included Group I of conventional round shape module with reduced friction coating i.e. super slick and synergy and Group II contained figure of "8" shape module i.e. Octavia ties and Slide ligature. RESULT: The mean static friction force and dynamic friction force for all 7 types of wires was lower in Group II (C, D) combined compared to Group I (A, B) and the difference was statistically very highly significant (p<0.001). CONCLUSION: Super slick and synergy can be used in the initial and final phase of treatment when full engagement of archwire in the bracket slot is necessary for proper tip and torque expression. Slide and Octavia ties modules can be used in the premolar brackets during en mass retraction when using friction mechanics. PMID- 27190945 TI - A Comparative and a Qualitative Analysis of Patient's Motivations, Expectations and Satisfaction with Dental Implants. AB - INTRODUCTION: Dental Implants are the norm of today's prosthetic and restorative dentistry but, is it the answer for edentulism that can affect both individual's appearance and functioning, therefore having an impact on the psychological and the social well being of the person is an ongoing quest. Also, patient's beliefs and personal expectations for dental implants vary, which may influence the treatment outcome, thus emphasizing the importance of a good clinician-patient communication. Hence in this study a qualitative analysis was carried out with an earnest attempt to gain an insight into patient's motivations, personal expectations, satisfaction and impact of clinician's motivation for implant maintenance. AIM: To learn about patient's expectations and their level of satisfaction from dental implants. To know the impact of clinician's instructions and motivation for implant maintenance, with the patient's level of understanding and compare the level of motivation for implant maintenance and care provided by a dentist with Bachelor's degree to a dentist with a Master's degree. MATERIALS AND METHODS: A 30 systemically healthy patients who had undergone implant treatment (aged 25-65 years) were considered and divided into two groups: Group A: 15 patients in whom implant placement was done by a dentist with Bachelor's degree (24 years, 18 years in general and implant practice respectively) and Group B: 15 patients in whom implant placement was done by a dentist with a Master's degree (Periodontics; 20 years,17 years in general and implant practice respectively). A qualitative analysis with the help of appropriate questionnaires comprising of multiple choice questions specifically designed for this purpose and few open ended questions was carried out with an earnest attempt to gain an insight into patient's motivations, personal expectations, satisfaction and impact of clinician's motivation for implant maintenance. RESULTS: Patients motivations for seeking implants and their expectations of treatment differed. Dental implants had met the patient's pre-treatment expectations and they were satisfied. Variations in the knowledge on the maintenance of the implants by the patients and the kind of maintenance care provided by the dentists varied between the two groups. CONCLUSION: In regard to the patient's compliance towards dental implants, a clinician must ensure that patient's understand the different demands. PMID- 27190946 TI - A Custom Made Intrinsic Silicone Shade Guide for Indian Population. AB - INTRODUCTION: Replication of natural skin colour in maxillofacial prosthesis has been traditionally done using trial and error method, as concrete shade guides are unavailable till date. Hence a novel custom made intrinsic silicone shade guide has been attempted for Indian population. AIM: Reconstruction of maxillofacial defects is challenging, as achieving an aesthetic result is not always easy. A concoction of a novel intrinsic silicone shade guide was contemplated for the study and its reproducibility in clinical practice was analysed. MATERIALS AND METHODS: Medical grade room temperature vulcanising silicone was used for the fabrication of shade tabs. The shade guide consisted of three main groups I, II and III which were divided based upon the hues yellow, red and blue respectively. Five distinct intrinsic pigments were added in definite proportions to subdivide each group of different values from lighter to darker shades. A total number of 15 circular shade tabs comprised the guide. To validate the usage of the guide, visual assessment of colour matching was done by four investigators to investigate the consent of perfect colour correspondence. Data was statistically analysed using kappa coefficients. RESULTS: The kappa values were found to be 0.47 to 0.78 for yellow based group I, 0.13 to 0.65 for red based group II, and 0.07 to 0.36 for blue based group III. This revealed that the shade tabs of yellow and red based hues matched well and showed a statistically good colour matching. CONCLUSION: This intrinsic silicone shade guide can be effectively utilised for fabrication of maxillofacial prosthesis with silicone in Indian population. A transparent colour formula with definite proportioning of intrinsic pigments is provided for obtaining an aesthetic match to skin tone. PMID- 27190947 TI - Wispy Prosthesis: A Novel Method in Denture Weight Reduction. AB - INTRODUCTION: Stability and retention of the denture becomes at stake with the increase in weight of the denture prosthesis. As a consequence, different materials and methods have been introduced to overcome these issues but denture weight reduction still remains to be a cumbersome and strenuous procedure. AIM: To introduce a novel technique for the fabrication of denture prosthesis where in the weight of the denture will not affect the retention and stability of the denture. MATERIALS AND METHODS: Four groups with a sample size of 10 each, were included where in one group was control and other three were study groups. The control group samples were made completely solid and the study group samples were packed with materials like bean balls, cellulose balls and polyacrylic fibers. The weight of all the samples of each study group was measured and compared with the control group. The observations were analyzed statistically by paired t-test. RESULTS: It was observed that the bean balls group produced a weight reduction of 31.3%, cellulose balls group 27.4% and polyacrylic fibers group 24.5% when compared to that of the control group. CONCLUSION: This novel technique will eliminate the problems that were associated in creating hollowness and at the same time will reduce the weight of the prosthesis and among all the study groups, bean balls group were found to reduce maximum weight of the prosthesis. PMID- 27190948 TI - Evaluation of the Quality of Obturation with Obtura at Different Sizes of Apical Preparation Through Microleakage Testing. AB - INTRODUCTION: Obturation of the root canal system is required to prevent recontamination of the root canal after cleaning and shaping procedures and to seal the root canal completely, both the apical and coronal avenues of potential leakage and to maintain the disinfected status. AIM: The aim of this study was to determine the microleakage by dye leakage method at 1mm, 3mm and 5mm short of the apex with different sizes of apical preparation, obturated by Obtura. MATERIALS AND METHODS: Sixty freshly extracted human single rooted teeth were randomly distributed into six equal groups. Group I (control group) was obturated by lateral compaction technique. Group II to VI were experimental groups (apical preparations done upto ISO sizes 20, 30, 40, 50 and 60 respectively), obturated by Obtura technique. After storing the samples at 100% humidity for seven days and one day in 2% methylene blue, the roots of the teeth were sectioned at 3mm short of the apex. They were observed under stereomicroscope at 20X magnification and the images were analysed for microleakage using the scoring criteria. The data obtained were analysed by One-way ANOVA followed by Tukey pair-wise multiple comparison test and p <= 0.05 was considered as the level of significance. RESULTS: The lowest mean microleakage score was seen in Group VI (0) and the highest mean leakage score was seen in Group II (1.5). There was statistically significant difference between Group II and Group V (p = 0.044), Group II and Group VI (p = 0.013). There was no significant difference between all the other groups (p> 0.05). CONCLUSION: Comparison of microleakage between different groups from ISO sizes 20-60 recommends a minimum apical preparation of ISO size 30. PMID- 27190949 TI - Recasting Disaster Recovery Strategy at Dental Workplace in Combating Crisis - A Questionnaire Study. AB - INTRODUCTION: The number of reported natural and human-made disasters continues to rise worldwide. Disasters occur every day somewhere in the world with dramatic impact on individuals, families and communities. AIM: This study was designed to measure the knowledge, attitude and practices regarding disaster management among academicians and practitioners in Ghaziabad city. MATERIALS AND METHODS: A cross sectional study was conducted among 487 dentists. A questionnaire (15 items) measuring knowledge, attitude and practice was distributed manually to the participating dentists and data was analysed using SPSS software, version 19.0 and student t-test was performed to assess the differences. RESULTS: There was statistically significant relation between knowledge and attitude in relation to qualification degree, career prospective and years of experience (p <0.05). CONCLUSION: Dentists form an important part of the health care community and thus there is a need to harvest the services of wide distribution of dentists practicing in our country. PMID- 27190950 TI - A Comparison of the Effectiveness of Oral Midazolam -N2O Versus Oral Ketamine - N2O in Pediatric Patients-An in-Vivo Study. AB - INTRODUCTION: Most children are casual and moderately agreeable in the dental treatment environment, however some of them show practices that upset the professional and make the protected conveyance of worthy treatment extremely troublesome. For such cases dental practitioner utilizes behavior management techniques. At the point when behavioral administration procedures come up short, some type of pharmacologic sedation or anesthesia may be an important and vital option. Dental sedation is a strategy in which the utilization of a medication or drugs produce(s) a condition of depression of the central sensory system empowering treatment to be completed during which verbal contact with the patient is kept up all through the time of sedation. AIM: This study was designed to evaluate and compare the effectiveness of oral midazolam and oral ketamine in combination with N2O-O2 in children undergoing dental treatment. MATERIALS AND METHODS: This study involved a sample of 30 pediatric dental patients (age range is 3-9 years), whose selection criteria included ASA I & II health status, cooperative but apprehensive behavior and a need for multiple dental extractions. The patients were assigned to receive oral midazolam on their first visit and on the follow up visit they received oral ketamine. Nitrous oxide (30%) was used during each sedation visit. Physiological parameters like Respiratory Rate (RR), pulse rate, and oxygen saturation were evaluated for each procedure, followed by the use of modified Bender Visual Motor Gestalt Test to evaluate psychomotor effects. Data were analyzed using Independent sample student t -test. RESULTS: Analysis of the data showed statistically no significant difference (p >0.05) on comparison of effectiveness of oral midazolam-N2O with oral ketamine-N2O when pulse rate, oxygen saturation and respiratory rate were taken into consideration. Psychomotor performance was found to be marginally better with oral midazolam-N2O compared to oral ketamine-N2O. CONCLUSION: Both the drugs were effective in reducing the patient anxiety while undergoing dental extractions. Though the t test results were not statistically significant with respect to physiological parameters. Oral midazolam-N2O showed marginally better results compared to oral ketamine-N2O with respect to psychomotor effects. PMID- 27190951 TI - Marquardt's Facial Golden Decagon Mask and Its Fitness with South Indian Facial Traits. AB - INTRODUCTION: The mathematical ratio of 1:1.618 which is famously known as golden ratio seems to appear recurrently in beautiful things in nature as well as in other things that are seen as beautiful. Dr. Marquardt developed a facial golden mask that contains and includes all of the one-dimensional and two-dimensional geometric golden elements formed from the golden ratio and he claimed that beauty is universal, beautiful faces conforms to the facial golden mask regardless of sex and race. AIM: The purpose of this study was to evaluate the goodness of fit of the golden facial mask with the South Indian facial traits. MATERIALS AND METHODS: A total of 150 subjects (75 males & 75 females) with attractive faces were selected with cephalometric orthodontic standards of a skeletal class I relation. The facial aesthetics was confirmed by the aesthetic evaluation of the frontal photographs of the subjects by a panel of ten evaluators including five orthodontists and five maxillofacial surgeons. The well-proportioned photographs were superimposed with the Golden mask along the reference lines, to evaluate the goodness of fit. RESULTS: South Indian males and females invariably show a wider inter-zygomatic and inter-gonial width than the golden mask. Most of the South Indian females and males show decreased mid-facial height compared to the golden mask, while the total facial height is more or less equal to the golden mask. CONCLUSION: Ethnic or individual discrepancies cannot be totally ignored as in our study the mask did not fit exactly with the South Indian facial traits but, the beauty ratios came closer to those of the mask. To overcome this difficulty, there is a need to develop variants of golden facial mask for different ethnic groups. PMID- 27190952 TI - Papillary Height and its Relation with Interproximal Distances and Cementoenamel Junction in Subjects with Chronic Periodontitis. A Cross-Sectional Study. AB - INTRODUCTION: Presence of intact interdental papilla is considered as an essential component of aesthetic dentistry. Loss or absence of interdental papilla creates black triangles which are unpleasing. AIM: The purpose of the present study was to determine relation of interproximal distances and cementoenamel junction with the classification of interdental papilla recession after surgical exposure in chronic periodontitis patients. MATERIALS AND METHODS: This cross-sectional, single masked study group involved 198 interdental papillae in 50 chronic periodontitis patients subjected to open flap debridement. The subjects were divided into three groups according to loss of height of interdental papillae: Class I papilla, Class II papilla, Class III papilla. The interproximal distances included vertical and horizontal distance. The vertical distance was measured from apical point of the contact area to alveolar crest; horizontal distance was measured between roots at the alveolar crest. Distance from mid buccal cementoenamel junction to apical point of the contact area was also measured. RESULTS: The vertical distance was found to be significantly affecting all the classes of loss of papillary height (p<0.05). Significantly positive correlation was found between vertical distance and buccal cementoenamel junction (p<0.05). On applying multiple linear regressions vertical distance was found to be strongest determinant of loss of papillary height. CONCLUSION: Although interproximal distances and cementoenamel junction affect the height of interdental papilla, other factors influencing the existence of interdental papilla should also be taken into consideration for treatment planning to achieve better aesthetics. PMID- 27190954 TI - Retention of Implant Supported Metal Crowns Cemented with Different Luting Agents: A Comparative Invitro Study. AB - INTRODUCTION: To overcome limitations of screw-retained prostheses, cement retained prostheses have become the restoration of choice now a days. Selection of the cement hence becomes very critical to maintain retrievability of the prostheses. AIM: The purpose of this study was to assess and compare the retention of base metal crowns cemented to implant abutments with five different luting cements. MATERIALS AND METHODS: Ten implant analogs were secured in five epoxy resin casts perpendicular to the plane of cast in right first molar and left first molar region and implant abutments were screwed. Total of 100 metal copings were fabricated and cemented. The cements used were zinc phosphate, resin modified glass ionomer cement, resin cement, non-eugenol acrylic based temporary implant cement & non-eugenol temporary resin cement implant cement. Samples were subjected to a pull-out test using an Instron universal testing machine at a crosshead speed of 0.5mm/min. The load required to de-cement each coping was recorded and mean values for each group calculated and put to statistical analysis. RESULTS: The results showed that resin cement has the highest retention value 581.075N followed by zinc phosphate luting cement 529.48N, resin modified glass ionomer cement 338.095 N, non-eugenol acrylic based temporary implant cement 249.045 N and non-eugenol temporary resin implant cement 140.49N. CONCLUSION: Within the limitations of study, it was concluded that non-eugenol acrylic based temporary implant cement and non-eugenol temporary resin implant cement allow for easy retrievability of the prosthesis in case of any failure in future. These are suitable for cement retained implant restorations. The results provide a possible preliminary ranking of luting agents based on their ability to retain an implant-supported prosthesis and facilitate easy retrieval. PMID- 27190953 TI - Assessment and Evaluation of Quality of Life (OHRQoL) of Patients with Dental Implants Using the Oral Health Impact Profile (OHIP-14) - A Clinical Study. AB - INTRODUCTION: Peri-implant tissue health is a requisite for success of dental implant therapy. Plaque accumulation leads to initiation of gingivitis around natural teeth and peri-implantitis around dental implants. Peri-implantitis around dental implants may result in implant placement failure. For obtaining long-term success, timely assessment of dental implant site is mandatory. AIM: To assess and evaluate Quality of Life (OHRQoL) of individuals with dental implants using the Oral Health Impact Profile (OHIP-14). MATERIALS AND METHODS: Total 92 patients were evaluated for assessment of the health of peri-implant tissues by recording, Plaque Index (PI), Probing Pocket Depth (PD), Bleeding On Probing (BOP) and Probing Attachment Level (PAL) as compared to contra-lateral natural teeth (control). In the same patients Quality of Life Assessment was done by utilizing Oral Health Impact Profile Index (OHIP-14). RESULTS: The mean plaque index around natural teeth was more compared to implants and it was statistically significant. Other three dimensions mean bleeding on probing; mean probing attachment level and mean pocket depth around both natural teeth and implant surfaces was found to be not statistically significant. OHIP-14 revealed that patients with dental implants were satisfied with their Oral Health-Related Quality of Life (OHRQoL). CONCLUSION: Similar inflammatory conditions are present around both natural teeth and implant prostheses as suggested by results of mean plaque index, mean bleeding on probing, mean pocket depth and mean probing attachment level, hence reinforcing the periodontal health maintenance both prior to and after incorporation of dental implants. Influence of implant prostheses on patient's oral health related quality of life (as depicted by OHIP-14) and patients' perceptions and expectations may guide the clinician in providing the best implant services. PMID- 27190955 TI - Tumour-Associated Tissue Eosinophilia in Oral Squamous Cell Carcinoma- A Boon or a Bane? AB - INTRODUCTION: The infiltration of tumour stroma by eosinophils, Tumour-Associated Tissue Eosinophilia (TATE) is known to modulate the evolution of Oral Squamous Cell Carcinoma (OSCC). Identification of eosinophils in the inflammatory stroma has been proven to be an important factor in prognostication of malignant tumours including cancers of mouth, oesophagus, larynx, pharynx, breast, lung, intestine and genitourinary tract. AIM: Our study aimed to assess the role of TATE as a prognosticator in OSCC as visualized by Haematoxylin and Eosin (H&E) and congo red staining. MATERIALS AND METHODS: Thirty histologically-proven cases of OSCC were retrieved from the archives of Department of Oral Pathology, Manipal College of Dental Sciences, Mangalore, Manipal University, Karnataka, India. Two serial sections of 4MUm thickness were made and subjected to routine staining with H&E and modified congo red staining, where eosinophil granules stained red and nuclei stained blue. In 40x magnification, 10 HPF at invasive tumour front were assessed for counting eosinophils by placing a 49 square grid (measuring 0.0289 sq mm). STATISTICAL ANALYSIS: The TATE was compared with the prognosticators using Mann Whitney U-test. The grades of carcinoma were correlated with TATE using Kruskal Wallis test followed by Post-hoc Bonferronis correction. Agreement of the number of eosinophils counted in the two staining techniques (H&E and Congo red) in OSCC was achieved using interclass correlation coefficient, and Friedman's test. A value of p< 0.05 was considered statistically significant. RESULTS: Our results showed that tissue eosinophil counts were higher in well-differentiated cases of OSCC, cases with lymph node involvement, decreased survival, without margin involvement and in cases that did not recur. H&E stain showed significantly better visualization of eosinophils resulting in higher eosinophil counts than when seen with Congo red (p=0.008). CONCLUSION: Thus, TATE can be used as a surrogate marker in prediction of survival and recurrence in OSCC. H&E proved to be a better stain for evaluation of eosinophils. PMID- 27190956 TI - Comparative Evaluation of Antimicrobial Effect of Three Endodontic Sealers with and Without Antibiotics - An In-vitro Study. AB - INTRODUCTION: Root canal sealers with good sealing ability and antimicrobial activity are desired to entomb the surviving microorganisms. AIM: Aim of the present study is to evaluate the antimicrobial effect of different sealers mixed with antibiotics. MATERIALS AND METHODS: Sixty extracted premolars were taken and were cut coronally & apically such that 7mm of tooth specimen was prepared. They were sterilized by autoclaving, inoculated with E.faecalis and incubated for three weeks. The specimens were divided into six groups of 10 each. Group 1 - ZnOE, Group 2 - ZnOE +TAM, Group 3 - Apexit Plus, Group 4 - Apexit Plus +TAM, Group 5 - AH Plus, Group 6 - AH Plus + TAM. Bacterial growth in the each specimen was calculated before & after sealer application and noted as initial & final colony count. Antimicrobial effect of each sealer was measured by calculating the Percentage Reduction in Colony Count (%RCC). One way analysis of variance and post hoc tests were used for statistical analysis. RESULTS: ZnOE + TAM group showed maximum antibacterial effect among the sealers tested and AH Plus sealer showed least antimicrobial effect. CONCLUSION: When the sealers were mixed with triple antibiotic mixture the antimicrobial effect was increased significantly. PMID- 27190957 TI - Invitro Evaluation of Fluoride Release from Hydroxyapatite Reinforced Glass Ionomer with or without Protective Coating. AB - INTRODUCTION: Glass Ionomer Cement (GIC) is well known for its fluoride releasing property but has its own drawbacks of poor mechanical properties, sensitivity to initial desiccation and moisture contamination. To overcome these, search led to the reinforcement of hydroxyapatite and application of surface coating agent but their effect on fluoride release is still not clear. AIM: To evaluate and compare the release of fluoride from Hydroxyapatite Reinforced Glass Ionomer (HA-GIC) with and without protective coating. MATERIALS AND METHODS: Specimens were prepared as follows- Eight percent by weight conventional glass ionomer was replaced by hydroxyapatite powder (HA) and an indigenous product was prepared (HA GIC). This powder was mixed with liquid of conventional GIC and allowed to set, then G coat plus coating agent was applied in surface coated group and light cured. Fluoride release of the sample was measured every 24 hrs for seven days and weekly from 7(th) to 21(st) day using combination ion selective electrode. RESULTS: Mean values clearly reveal a significant decrease in the fluoride release from day 1 to day 21 for both the groups. Results of repeated measure ANOVA revealed statistically significant difference between two groups (p <0.001). CONCLUSION: Coating the hydroxyapatite reinforced glass ionomer will allow for slow and steady release of fluoride for a long period of time into oral environment. PMID- 27190958 TI - Management of Chronic Periodontitis Using Chlorhexidine Chip and Diode Laser-A Clinical Study. AB - INTRODUCTION: The use of adjuncts like chlorhexidine local delivery and diode laser decontamination have been found to improve the clinical outcomes of scaling and root planing in non-surgical periodontal therapy in patients with chronic periodontitis. AIM: To evaluate the effects of diode laser and chlorhexidine chip as adjuncts to scaling and root planing in the management of chronic periodontitis. The objective is to evaluate the outcome of chlorhexidine chip and diode laser as adjuncts to scaling and root planing on clinical parameters like Plaque Index, Gingival Index, probing pocket depth and clinical attachment level. STUDY AND DESIGN: Department of Periodontics. Randomized clinical trial with split mouth design. MATERIALS AND METHODS: Fifteen chronic periodontitis patients having a probing pocket depth of 5mm-7mm on at least one interproximal site in each quadrant of the mouth were included in the study. After initial treatment, four sites in each patient were randomly subjected to scaling and root planing (control), chlorhexidine chip application (CHX chip group), diode laser (810 nm) decontamination (Diode laser group) or combination of both (Diode laser and chip group). Plaque Index (PI), Gingival Index (GI), probing pocket depth (PPD) and clinical attachment level (CAL) were assessed at baseline, one month and three months. STATISTICAL ANALYSIS: Results were statistically analysed using paired T test, one-way ANOVA, Tukey's HSD test and repeated measure ANOVA. RESULTS: Post treatment, the test and control sites showed a statistically significant reduction in PI, GI, PPD, and CAL. After three months, a mean PPD reduction of 1.47+/-0.52 mm in control group, 1.40+/-0.83 mm in diode laser group, 2.67+/-0.62 mm in CHX group, and 2.80+/- 0.77 mm in combination group was seen. The mean gain in CAL were 1.47+/-0.52 mm in the control group, 1.40+/-0.83 mm in diode laser group, 2.67+/- 0.49 mm in CHX group and 2.67+/- 0.82 mm in combination group respectively. The differences in PPD reduction and CAL gain between control group and CHX chip and combination groups were statistically significant (p<0.05) at three months, whereas, the diode laser group did not show any significant difference from the control group. CONCLUSION: Chlorhexidine local delivery alone or in combination with diode laser decontamination is effective in reducing probing pocket depth and improving clinical attachment levels when used as adjuncts to scaling and root planing in non-surgical periodontal therapy of patients with chronic periodontitis. PMID- 27190959 TI - Quantitative Assessment of Tumor Associated Macrophages in Head and Neck Squamous Cell Carcinoma Using CD68 Marker: An Immunohistochemical Study. AB - INTRODUCTION: Oral Squamous Cell Carcinoma (OSCC) is one of the most prevalent cancers in India. Clear evidence regarding inflammation being an etiological factor of cancer was found only in the last few decades. A major inflammatory component in the tumor tissue is Tumor-Associated Macrophages (TAMs). The CD68 antibody is a marker for staining TAMs. AIM: The aim of this study is to quantify the macrophage count in healthy oral mucosa and OSCC and comparing TAMs in different histopathological grades of OSCC immunohistochemically. MATERIALS AND METHODS: Thirty archival specimens of OSCC patients and 10 healthy biopsy samples were collected. Immunohistochemical staining was done using a CD68 marker. Statistical analysis was done using Kruskal-Wallis ANOVA and Mann-Whitney U test. RESULTS: Comparing CD68 expression in various study groups showed a significant difference (p=0.000). The pair-wise analysis showed different grades of OSCC, which differed significantly for CD68 expression from the normal oral mucosa. CONCLUSION: The most significant cells present in tumor stroma are TAMs, which remain in close proximity to neoplastic cells and interact with them via several chemical mediators, which may serve to increase the invasiveness of the malignant epithelium. Dense infiltration of TAMs adjacent to tumor cells and islands vividly implies their role in tumor progression. PMID- 27190961 TI - Antibacterial Activity and Fluoride Release of Glass-Ionomer Cement, Compomer and Zirconia Reinforced Glass-Ionomer Cement. AB - INTRODUCTION: The cariostatic property of glass ionomer cement (GIC) stems from its ability to release fluoride into the oral environment. Recently, zirconia reinforced GIC has been launched which promises the protective benefits of glass ionomer while completely eliminating the hazard of mercury. AIM: To evaluate invitro antibacterial activity and fluoride release from two conventional glass ionomer cements (GC II and GC IX), compomer (Compoglass) and a zirconia reinforced glass ionomer cement (Zirconomer). MATERIALS AND METHODS: The antibacterial activity of the cement specimens was evaluated against Streptococcus mutans using the agar inhibition test. Zone of inhibition on Mueller-Hinton agar plates was measured after 48 hours. The fluoride release from the cement specimens in ppm were measured at day 1, 7, 14 and 21 using a fluoride ion selective electrode. Data was analysed using one-way and two-way analysis of variance (ANOVA) followed by LSD post-hoc test. A p-value <0.05 was considered statistically significant. RESULTS: Statistically significant largest zone of inhibition was observed with Zirconomer. Also, significant differences were seen in fluoride release of different materials. At all the time intervals maximum fluoride release was observed with Zirconomer and minimum with Compoglass. CONCLUSION: This invitro investigation has revealed that zirconia reinforced GIC (Zirconomer) had maximum antibacterial activity against S.mutans and fluoride release. PMID- 27190960 TI - Effect of Green and White Tea Pretreatment on Remineralization of Demineralized Dentin by CPP-ACFP-An Invitro Microhardness Analysis. AB - INTRODUCTION: Mechanical performance of dentine is of major significance for the overall function of the teeth. Remineralization of carious dentine is the ultimate goal in re-establishing the functionality of the affected tissue so as to regain and maintain the mechanical properties of dentine. Functional remineralization of the affected dentin involves stabilization of both inorganic and organic component, but Caesin Phosphopeptide Amorphous Calcium Flurophosphate (CPP-ACFP) stabilizes only inorganic content. Hence to stabilize organic content and to bring in functional remineralization the use of anticollagenolytic and antielastastic agent was considered for this study. AIM: To assess and compare the remineralization of artificial carious dentin pre treated with white and green tea, before and after application of CPP-ACFP using microhardness test. Null hypothesis was that both teas did not have any effect on remineralization potential of CPP ACFP. MATERIALS AND METHODS: Forty specimens were subjected to artificial caries lesions and were randomly divided into 4 groups based on the application of tea extract followed by CPP-ACFP (groups A & B) and CPP-ACFP followed by tea extracts (groups C & D). All the specimens were subjected to two pH cycling regimen. The specimens were subjected to Vickers microhardness test to obtain the microhardness values. The values were statistically analysed using one way ANOVA and multiple comparisons with Tukey's HSD procedure. RESULTS: After the 1(st) and 2(nd) pH cycling in groups A and B, Group B showed significant increase in microhardness values (35.79+/- 3.12 VHN). But after the pH cycling regimen in groups C and D, microhardness values increased in 1(st) pH cycling (50.03+/- 3.64 VHN); (50.03+/-3.64 VHN), respectively but decreased during the 2(nd) pH cycling, (33.94+/-6.45 VHN); (33.11+/-6.11 VHN) respectively with the level of significance <0.05. CONCLUSION: The results of this study rejects the hypothesis tested and showed that both the tea extracts increased the microharness values when used prior to the application of remineralizing agent. However, 10% white tea showed better microhardness indicating stabilization of collagen in dentine resulting in functional remineralization. PMID- 27190962 TI - Demystifying the Enigma of Smoking - An Observational Comparative Study on Tobacco Smoking. AB - INTRODUCTION: Smoking is a hazardous habit which causes definite changes in the oral cavity, consequently there exist changes in the mucosa when subjected to smoking. Palatal mucosa is first to be affected. The present study determines the palatal status in reverse smokers and conventional smokers. AIM: To study and compare the clinical, cytological and histopathological changes in palatal mucosa among reverse and conventional smokers. MATERIALS AND METHODS: Study sample was categorized into two groups. Group 1 comprised of 20 subjects with the habit of reverse smoking and Group 2 comprised of 20 subjects with the habit of conventional smoking. Initially, clinical appearance of the palatal mucosa was recorded, followed by a cytological smear and biopsy of the involved area among all the subjects. The findings were studied clinically, the specimens were analysed cytologically and histopathologically, and compared among the two groups. RESULTS: The severity of clinical changes of the palatal mucosa among reverse smokers was statistically significant when compared to those of conventional smokers. There was no statistically significant difference observed in cytological staging between the groups with a p-value of 0.35. The histopathological changes in both the groups showed a significant difference with a p-value of 0.02. A significant positive correlation was observed between the clinical appearance, and cytological, histopathological changes. CONCLUSION: Profound clinically aggressive changes were observed in group I compared to group II. Severity of dysplastic changes have been detected in few subjects through histopathological examination irrespective of no prominent clinical and cytological changes observed among the two groups. PMID- 27190963 TI - An Interesting Case of Penetrating Craniofacial Trauma Involving a Wooden Stick. AB - Penetrating craniofacial trauma, although uncommon, has a high potential for death or catastrophic consequences from head injury or vital neurovascular injuries. The foreign body may cause significant challenge, especially when it is a large one. Airway obstruction, vascular injuries, intracranial communication, ocular injury and injuries to any other adjacent vital structures when involved may change the treatment objectives from simple foreign body retrieval to a comprehensive multidisciplinary approach to stabilize the patient. Retrieval of foreign bodies may be challenging because of many factors including the size of the object, its site, and the surrounding anatomical structures. Accurate localization of the foreign body before removal is essential in craniofacial region. We present a case of penetrating craniofacial trauma from a wooden stick, with an in situ foreign body, that was managed by emergency surgical exploration in general anaesthesia and retrieval of foreign body in Toto under antibiotic coverage and tetanus prophylaxis. PMID- 27190964 TI - Fibrofascitis - An Enigma for the Dentist: A Case Report. AB - Fibromyalgia is a chronic syndrome that causes widespread musculoskeletal pain and stiffness throughout the connective tissues that support and move the bones and joints. Pain and localized tender points occur in the muscles, particularly those that support the neck, spine, shoulders, and hips. Moreover the disorder includes fatigue, depression, sleep disturbances and constipation. A combination of treatments including medications, patient education, physical therapy and counseling are usually recommended. Here, we present a case report of fibromyalgia and the treatment given to the patient, a combination of dental and orthopedic treatment. PMID- 27190965 TI - Non Aggressive Mandibular Osteoblastoma- A Rare Maxillofacial Entity. AB - Benign osteoblastoma is a very rare, bone tumour occurring in the facial region. These lesions are most frequently seen in long bones. They are characterised by proliferation of compact or cancellous bone. The lesion is usually asymptomatic until it causes significant facial asymmetry or displacement of the teeth if present in the alveolar region. The clinical appearance of osteoblastoma is very similar to peripheral ossifying fibroma or any fibro-osseous lesion. The tumour is characterised by bone formation along with the presence of numerous osteoblasts. This case report describes the presence of a bony hard mass in the right side of mandible of a 27-year-old female patient with the chief complaint of a painless growth since past 10 years. The growth slowly increased in size displacing the teeth associated with it. The patient also complained of difficulty in speech and mastication. PMID- 27190966 TI - A Novel Technique To Correct Multiplanar Maxillary Hypoplasia. AB - Dental malocclusion and facial deformity are frequent observations in patients with clefts of the orofacial region. These patients have a low self perception secondary to their aesthetic appearance. Cleft palate patients are further affected in their speech and oral function with direct impediment to their quality of life. Early identification and treatment in cleft lip and palate patients may directly enhance their overall well being and productivity with sustainable prognosis when managed by skilled and evidence informed operators. We present a successful case management of a patient with a cleft palate and dentofacial deformity with a past surgical history, treated with an anterior maxillary advancement osteotomy, stabilized with an interpositional non vascular iliac bone graft. The posterior open bite was corrected using overlay full coverage crowns. Both these techniques are rarely reported in the literature. The procedure positively improved the quality of life in our patient with regards to her aesthetics, speech and function. This treatment approach could be considered in similar cases to achieve predictable outcomes. PMID- 27190967 TI - Diffuse Large B-Cell Lymphoma of Maxilla - A Case Report of Late Relapse. AB - Diffuse Large B Cell Lymphomas (DLBCL) encompasses a heterogeneous group of tumors that together constitute the commonest of all Non Hodgkin Lymphoma (NHL) and the proclivity of DLBCL to oral cavity is unknown. They mostly arise from soft tissues as asymptomatic lesions, mostly without 'B' symptoms and involvement of jaw bones is uncommon. Most studies and case reports of oral DLBCL's are based on, manifestation of primary extra-nodal disease or a component of a disseminated disease process involving regional lymph nodes. Many investigators have proposed that patients with this cell type who maintain a complete response for 24 consecutive months are cured because late relapses seldom occur. With advances in treatment modalities, many patients with NHL become long-term survivors and the risk of relapses or second tumors are of growing concern. We present a case of DLBCL which relapsed after five years of initial lesion in a 41 year old female patient and presented as a nonspecific bilateral anterior maxillary radiolucency. DLBCL usually express pan-B markers with small percentage expressing T-cell markers. Few rare cases of DLBCL have shown CD3 expression, which is a most sensitive T-cell marker which was focally expressed in the present case. PMID- 27190968 TI - Role of Orthodontics in Forensic Odontology- A Social Responsibility. AB - Orthodontics like any other specialty has much to offer law enforcement in the detection and solution of crime or in civil proceedings. Forensic odontology often requires an interdisciplinary approach towards dentistry for the purpose of proper diagnosis of cases. In cases where the forensic odontologist has to establish a person's identity, an orthodontist can be of great help at times. Teeth, with their anatomic/physiologic variations and therapy such as orthodontic treatment, restorations and prosthesis may record information that remains throughout life and beyond. The teeth may also be used as weapons for defense or offense and as such may leave information about the identity of the biter at the time of crime. Forensic odontology also plays an important role in the recognition of crime and abuse among people of all ages. Orthodontists like all other dental professionals can play a major role by maintaining proper dental records and thus providing important or vital information or clues to the legal authorities in order to help them in their search. PMID- 27190970 TI - Novel Matricing Technique for Management of Fractured Cusp Conundrum - A Clinician's Corner. AB - Longitudinal tooth fracture can be classified as craze lines, fractured cusp, cracked tooth, split tooth and vertical root fracture based on extent and severity of the fracture line. The most common type of longitudinal tooth fracture is fractured cusp that poses the treatment dilemma. Retention of the fractured cusp segment temporarily with matrix band followed by permanent bonded restoration and finally removal of tooth fragment during crown preparation is a novel technique. This paper throws light on a matricing and holding technique for the management of supra-crestally fractured palatal cusp of maxillary first premolar in a 29-year-old Asian male. PMID- 27190969 TI - LongoVital- An Imminent Therapeutic Modality: An Unseen Drug Review with Advanced Features and Hypothesis. AB - Herbal medication still happens to be the backbone of the major world's population essentially because of the assumption that these drugs are free of any side effects and easily available. LongoVital (LV) is a herbal preparation with documented immune-modulatory and immune-stimulatory effects in man. Various studies conducted to date, have shown LV to have prolonged and beneficial impact in the treatment of orofacial diseases, when administered in recommended daily doses. With its combined antimicrobial and immunostimulatory effects, LV can be regarded as an emerging therapeutic modality in the treatment of orofacial diseases. PMID- 27190971 TI - A Innovative Technique - Modified Feeding Bottle for a Cleft Palate Infant. AB - Cleft lip and cleft palate are one of the most common craniofacial anomalies. Infants suffer a lot of difficulty in sucking during the initial few days after birth. There is even psychological stress to the parents due to improper feeding and the infants lose weight and are prone to nutritional insufficiency. Due to recent advancement in the medical field, there is a total repair of cleft lip and cleft palate and these procedures are performed in the later stages of infants. It is the multidisciplinary approach which includes pedodontist, oral surgeon, prosthodontist and speech therapist. In this article, the technique is highlighted to fulfill the feeding problem of infants in the early stages of birth with a modified feeding bottle. PMID- 27190972 TI - Radiographic Assessment of Bone Formation Using rhBMP2 at Maxillary Periapical Surgical Defects: A Case Series. AB - Periapical cysts are the most common inflammatory odontogenic cysts arising from untreated dental caries with pulp necrosis and periapical infection. The choice of treatment is often influenced by various factors like size, extension of the lesion, proximity to vital structures, systemic condition and compliance of the patient too. The treatment protocol for management of periapical cysts is still under discussion and options vary from conservative treatment by means of endodontic technique to surgical treatment like decompression or a marsupialisation or even to enucleation. Large bony defect secondary to periapical surgery compromising the tooth integrity often requires bone graft to enhance bone formation and thus restoring function at the earliest. The present case series included 10 patients who had established periapical pathology secondary to history of trauma on upper anterior teeth as well patients with history of carious teeth with an apparent failure in root canal therapy. All ten patients were treated with cyst enucleation and apiceotomy along with 1.4cc Recombinant Human Bone Morphogenetic Protein-2 soaked Absorbable Collagen Sponge implantation at surgical defect. Radiographs and clinical examinations were done upto 3 months to evaluate healing. Radiographic and clinical assessments revealed bone regeneration and restoration of the maxillary surgical defects in all 10 patients. No evidence of graft failure was noted. The Recombinant Human Bone Morphogenetic Protein-2 soaked Absorbable Collagen Sponge carrier is thus proved to be a viable option for the treatment of maxillary periapical surgical defects. PMID- 27190973 TI - Transforming Health Professionals into Population Health Change Agents. AB - BACKGROUND: With the recognition that professional education has not kept pace with the challenges facing the health and human service system, there has been a move to transformative education and learning professional development designed to expand the number of enlightened and empowered change agents with the competence to implement changes at an individual, organisation and systems level. DESIGN AND METHODS: Since 2010, the Department of Health and Human Services in Victoria, Australia, in collaboration with The University of Melbourne's School of Population and Global Health, has delivered seven population health short courses aimed to catalyse participants' transformation into population health change agents. This paper presents key learnings from a combination of evaluation data from six population health short courses using a transformative learning framework from a 2010 independent international commission for health professionals that was designed to support the goals of transformative and interdependent health professionals. Participatory realist evaluation approaches and qualitative methods were used. RESULTS: Evaluation findings reveal that there were mixed outcomes in facilitating participants' implementation of population health approaches, and their transformation into population health agents upon their return to their workplaces. Core enablers, barriers and requirements, at individual, organisational and system levels influence the capability of participants to implement population health approaches. The iterative and systemic evolution of the population health short courses, from a one off event to a program of inter-dependent modules, demonstrates sustained commitment by the short course developers and organisers to the promotion of transformative population health learning outcomes. CONCLUSIONS: To leverage this commitment, recognising that professional development is not an event but part of an ongoing transformative process, suggestions to further align recognition of population health professional development programs are presented. Significance for public healthWith decreasing health and wellbeing of whole populations, increasing inequities among specific population groups, health professional educators are increasingly turning their attention to population health. This has implications for implementing evidence into practice. Professional development short courses are being conducted to equip participants (health service managers, health promotion managers and coordinators, health planners, population health planners and senior executives) with knowledge, skills and tools to implement population health approaches and transform them into population health change agents. The findings of this study indicate there were mixed outcomes in facilitating participants' implementation of population health approaches and their transformation into population health agents upon their return to their workplaces. The study findings informed the evolution of the short courses, from a one off event to a program of interdependent modules, and further reveal that professional development is not an event but part of an on-going transformative process,suggestions to further align recognition of population health professional development programs are presented. PMID- 27190974 TI - A Student-Led Global Health Education Initiative: Reflections on the Kenyan Village Medical Education Program. AB - The Kenyan Village Medical Education Program is a student-led global health initiative that seeks to improve health outcomes in rural Kenya through culturally appropriate health education. The month-long program, which is organised by the Melbourne University Health Initiative (Australia), is conducted each January in southern rural Kenya. Significance for public healthThe Kenyan Village Medical Education (KVME) Program is a student-led global health initiative that involves exploring well-established strategies for the prevention of disease through workshops that are conducted in southern rural Kenya. These workshops are tailored to the unique needs and circumstances of rural Kenyan communities, and are delivered to community leaders, as well as to adults and children within the wider community. Aside from the KVME Program's emphasis on reducing the burden of preventable disease through health education, the positive impact of the KVME Program on the Program's student volunteers also deserves consideration. Throughout the month-long KVME Program, student volunteers are presented with opportunities to develop their understanding of cultural competency, the social and economic determinants of health, as well as the unique challenges associated with working in resource-poor communities. Importantly, the KVME Program also represents an avenue through which global health leadership can be fostered amongst student volunteers. PMID- 27190975 TI - Cultural Respect Encompassing Simulation Training: Being Heard About Health Through Broadband. AB - BACKGROUND: Cultural Respect Encompassing Simulation Training (CREST) is a learning program that uses simulation to provide health professional students and practitioners with strategies to communicate sensitively with culturally and linguistically diverse (CALD) patients. It consists of training modules with a cultural competency evaluation framework and CALD simulated patients to interact with trainees in immersive simulation scenarios. The aim of this study was to test the feasibility of expanding the delivery of CREST to rural Australia using live video streaming; and to investigate the fidelity of cultural sensitivity - defined within the process of cultural competency which includes awareness, knowledge, skills, encounters and desire - of the streamed simulations. DESIGN AND METHODS: In this mixed-methods evaluative study, health professional trainees were recruited at three rural academic campuses and one rural hospital to pilot CREST sessions via live video streaming and simulation from the city campus in 2014. Cultural competency, teaching and learning evaluations were conducted. RESULTS: Forty-five participants rated 26 reliable items before and after each session and reported statistically significant improvement in 4 of 5 cultural competency domains, particularly in cultural skills (P<0.05). Qualitative data indicated an overall acknowledgement amongst participants of the importance of communication training and the quality of the simulation training provided remotely by CREST. CONCLUSIONS: Cultural sensitivity education using live video streaming and simulation can contribute to health professionals' learning and is effective in improving cultural competency. CREST has the potential to be embedded within health professional curricula across Australian universities to address issues of health inequalities arising from a lack of cultural sensitivity training. Significance for public healthThere are significant health inequalities for migrant populations. They commonly have poorer access to health services and poorer health outcomes than the Australian-born population. The factors are multiple, complex and include language and cultural barriers. To address these disparities, culturally competent patient-centred care is increasingly recognised to be critical to improving care quality, patient satisfaction, patient compliance and patient outcomes. Yet there is a lack of quality in the teaching and learning of cultural competence in healthcare education curricula, particularly in rural settings where qualified trainers and resources can be limited. The Cultural Respect Encompassing Simulation Training (CREST) program offers opportunities to health professional students and practitioners to learn and develop communication skills with professionally trained culturally and linguistically diverse simulated patients who contribute their experiences and health perspectives. It has already been shown to contribute to health professionals' learning and is effective in improving cultural competency in urban settings. This study demonstrates that CREST when delivered via live video streaming and simulation can achieve similar results in rural settings. PMID- 27190976 TI - Health Professional Workforce Education in the Asia Pacific. AB - OBJECTIVE: To design and implement an international and interprofessional Global Learning Partnership Model, which involves shared learning between academics and students from Universitas 21 network with other universities with United Nations Millennium Development Goal needs. DESIGN: Two literature reviews were conducted to inform ethical aspects and curriculum design of the GLP model. Feedback from conference presentations and consultation with experts in education and public health has been incorporated to inform the current iteration of the GLP model. INTERVENTION: The pilot group of 25 students from U21 universities and Kathmandu University, representing six health disciplines will meet in Nepal in April 2016 for a shared learning experience, including a one week university based workshop and three week community based experience. OUTCOME MEASURES: A multi-phase, mixed method design was selected for the evaluation of the GLP model, utilising a combination of focus groups and questionnaires to evaluate the efficacy of the placement through student experience and learning outcomes in cultural competency, UN SDG knowledge, community engagement and health promotion skills. RESULTS: The literature review demonstrated that cultural awareness and cultural knowledge were improved through participation in cultural immersion programs that incorporated preparatory workshops and clinical experiences. Data will be gathered in April 2006 and the results of the evaluation will be published in the future. CONCLUSIONS: The GLP model proposes a project around the fundamental concept of engagement and sharing between students and academics across universities and cultural contexts to build capacity through education, while capitalising on strengths of existing global health placements. Further the inclusion of host-country students and academics in this learning exchange will promote the establishment of an international and interprofessional network for ongoing health promotion. Significance for public healthThe Global Learning Partnership model aims to contribute to the capacity building of a health workforce that is capable of working effectively in cross cultural and interprofessional health care teams. A shared public health focused global placement has the potential to catalyse collaborative relationships between educational institutions in the Asia Pacific region. PMID- 27190977 TI - Public Health Platforms: An Emerging Informatics Approach to Health Professional Learning and Development. AB - Health informatics has a major role to play in optimising the management and use of data, information and knowledge in health systems. As health systems undergo digital transformation, it is important to consider informatics approaches not only to curriculum content but also to the design of learning environments and learning activities for health professional learning and development. An example of such an informatics approach is the use of large-scale, integrated public health platforms on the Internet as part of health professional learning and development. This article describes selected examples of such platforms, with a focus on how they may influence the direction of health professional learning and development. Significance for public healthThe landscape of healthcare systems, public health systems, health research systems and professional education systems is fragmented, with many gaps and silos. More sophistication in the management of health data, information, and knowledge, based on public health informatics expertise, is needed to tackle key issues of prevention, promotion and policy making. Platform technologies represent an emerging large-scale, highly integrated informatics approach to public health, combining the technologies of Internet, the web, the cloud, social technologies, remote sensing and/or mobile apps into an online infrastructure that can allow more synergies in work within and across these systems. Health professional curricula need updating so that the health workforce has a deep and critical understanding of the way that platform technologies are becoming the foundation of the health sector. PMID- 27190979 TI - A Community Engaged Dental Curriculum: A Rural Indigenous Outplacement Programme. AB - BACKGROUND: Indigenous people worldwide suffer from poor oral health as compared to non-Indigenous citizens. One of the approaches to bring about improvement in Indigenous oral health is to enhance the service provision by implementing oral health outplacement programmes. A case study of such a programme for dental students in Australia reports how an educational institution can successfully engage with an Indigenous oral health service to provide learning experiences to the students as well as deliver much needed services to the community. DESIGN AND METHODS: The assessment of this ongoing outplacement programme over the period of 2008-14, based on students' feedback, highlights some of the key beneficial outcomes. Students agreed that the Indigenous outplacement programme improved their understanding of Indigenous issues (mean +/- SD: 4.10+/-0.8; 5 refers to strongly agree on 5-point scale) and increased the possibility that they will practise in Indigenous health (3.66+/-1.0). They were pleased with the assistance received by clinical supervisors and clinic staff at the Indigenous dental clinic (4.28+/-0.8). CONCLUSIONS: This programme has demonstrated that structured student outplacements are valuable in building relations across cultures especially with Indigenous communities. It has also shown that university engagement with the public health sector can be beneficial to both institutions. Significance for public healthAn oral health outreach programme is one of the suggested approaches to effectively address the endemic issues of poor oral health among Indigenous people around the world. An Indigenous dental clinical outplacement in Australia provides an example of beneficial outcomes of such an approach. It provides dental students with an opportunity to experience the health issues related to Australian Indigenous communities and prepare future graduates to work comfortably in the public health care system. Indigenous people also develop trust and feel comfortable in receiving oral health care services from non-indigenous clinicians. PMID- 27190978 TI - Culturally and Linguistically Diverse Populations in Medical Research: Perceptions and Experiences of Older Italians, Their Families, Ethics Administrators and Researchers. AB - BACKGROUND: Low-participation of culturally and linguistically diverse (CALD) patients in medical research remains a problem in migrant and refugee destination countries such as Australia. The aims of this study were to explore i) CALD persons' perceptions and experiences of the medical system and medical research, in this case, older Italian Australians; and ii) the views of research professionals on CALD patient participation in medical research. DESIGN AND METHODS: A qualitative study was conducted in Melbourne, Australia, in 2015 utilising in-depth interviews and focus groups with four stakeholder groups: older Italian Australians (n=21); adult children of older Italian Australians (n=10); hospital Human Research Ethics Committee administrators (n=4); and clinical researchers (n=4). The data were analysed for content and thematic analysis. RESULTS: Themes for the CALD and family group were getting by in medical interactions; receptivity to medical research: testing the waters; and, receptivity to technology for support: passive versus active. Themes for the researcher and HREC groups about CALD patient participation in research were: exclusion; cultural factors; and e-consent. CONCLUSIONS: Our findings from four stakeholder perspectives and experiences confirm that there were considerable cultural, linguistic, and resourcing barriers hindering the participation of older Italian-Australians in medical research. Furthermore, our findings showed that in this study setting there were few enabling strategies in place to address these barriers despite the national ethics guidelines for equitable participation in research. The findings informed the creation of a multimedia tool whose purpose is to address and improve representation of CALD groups in clinical research. Significance for public healthMany people from culturally and linguistically diverse (CALD) backgrounds remain excluded from medical research such as clinical trials due to a range of language and cultural factors that can be amplified when this population is ageing. This exclusion has implications for the ability of CALD populations to benefit from participating in medical research and for applying research findings to CALD populations. It is essential to develop and implement strategies to include CALD communities in medical research and to uphold the ethical obligation of obtaining informed consent to research. The findings of this study have guided the development of a tablet-based resource which can be used in clinical and community contexts to raise awareness about the purpose of medical research. The resource has been carefully designed to be appropriate for participants' cultural background as well as their preferred language and literacy level. Such a resource has potential to address some of the cultural and linguistic barriers to clinical trial participation of CALD populations. PMID- 27190980 TI - Teaching About Climate Change in Medical Education: An Opportunity. AB - Climate change threatens many of the gains in development and health over the last century. However, it could also be a catalyst for a necessary societal transformation to a sustainable and healthy future. Doctors have a crucial role in climate change mitigation and health system adaptation to prepare for emergent health threats and a carbon-constrained future. This paper argues that climate change should be integrated into medical education for three reasons: first, to prepare students for clinical practice in a climate-changing world; secondly, to promote public health and eco-health literacy; and finally, to deepen existing learning and strengthen graduate attributes. This paper builds on existing literature and the authors' experience to outline potential learning objectives, teaching methods and assessment tasks. In the wake of recent progress at the United Nations climate change conference, COP-21, it is hoped that this paper will assist universities to integrate teaching about climate change into medical education. Significance for public healthThere is a strong case for teaching about climate change in medical education. Anthropogenic climate change is accepted by scientists, governments and health authorities internationally. Given the dire implications for human health, climate change is of fundamental relevance to future doctors. Integrating climate change into medical education offers an opportunity for future doctors to develop skills and insights essential for clinical practice and a public health role in a climate-changing world. This echoes a broader call for improved public health literacy among medical graduates. This paper provides medical schools with a rationale and an outline for teaching on climate change. PMID- 27190981 TI - Aboriginal and Torres Strait Islander Public Health: Online and Integrated into Core Master of Public Health Subjects. AB - The Master of Public Health (MPH) is an internationally recognised post-graduate qualification for building the public health workforce. In Australia, MPH graduate attributes include six Indigenous public health (IPH) competencies. The University of Melbourne MPH program includes five core subjects and ten specialisation streams, of which one is Indigenous health. Unless students complete this specialisation or electives in Indigenous health, it is possible for students to graduate without attaining the IPH competencies. To address this issue in a crowded and competitive curriculum an innovative approach to integrating the IPH competencies in core MPH subjects was developed. Five online modules that corresponded with the learning outcomes of the core public health subjects were developed, implemented and evaluated in 2015. This brief report outlines the conceptualisation, development, and description of the curriculum content; it also provides preliminary student evaluation and staff feedback on the integration project. Significance for public healthThis approach to a comprehensive, online, integrated Indigenous public health (IPH) curriculum is significant, as it ensures that all University of Melbourne Master of Public Health (MPH) graduates will have the competencies to positively contribute to Indigenous health status. A workforce that is attuned not only to the challenges of IPH, but also to the principles of self-determination, Indigenous agency and collaboration is better equipped to be comprised of ethical and judgment-safe practitioners. Additionally, the outlined approach of utilizing IPH content and examples into core MPH subjects ensures both the Australian relevance for an Australian-based health professional course and international appeal through the modules inclusion of International Indigenous case-studies and content. Furthermore, approaches learned in a challenging Indigenous Australian context are transferable and applicable to other IPH challenges in a local, national and global context. PMID- 27190982 TI - Learning About Self: Leadership Skills for Public Health. AB - As public health practitioners and as clinicians we are taught to care for our patients, and for our community members. But how much do we teach and learn about how to lead, manage and care for our colleagues, our team members and ourselves? This paper emphasizes the need for leadership learning and teaching to become an essential element of the practice of public health. The paper presents the author's perspective on the leadership skills required for public health and describes a five-day intensive course designed to enable participants to develop these skills over time. The paper briefly covers leadership definitions, styles and types and key leadership skills. It mainly focuses on the design and ethos of the course, skills self-assessment, group interaction and methods for developing and refining leadership skills. The course uses a collaborative learning approach where the power differential between teachers, facilitators, guests and participants is minimized. It is based on creating an environment where any participant can reveal his or her stories, successes, failures, preferences and dislikes in a safe manner. It encourages continual, constructive individual reflection, self-assessment and group interaction. The course is aimed at the practice of public health leadership, with a particular emphasis on the leadership of self, of knowing oneself, and of knowing and understanding colleagues retrospectively as well as prospectively. The most important outcome is the design and implementation of participants' own plans for developing and nurturing their leadership skills. Significance for public healthThe nature of public health is changing rapidly and increasing in complexity. These changes include major shifts in the burden of disease and the insatiable demands of clinical medicine swamping those of public health. Public health practitioners have failed over many years to systematically ensure that leadership and management skills are essential parts of public health training (as they are in MBAs for example). This paper describes an approach and an intensive five-day course to assist practitioners to develop the key leadership skills needed to improve public health, whether it be locally, nationally or globally. PMID- 27190983 TI - Putting Population and Global Health on the Agenda of Health Professionals. PMID- 27190984 TI - Comparison of Sexual Experience and Behavior between Bipolar Outpatients and Outpatients without Mood Disorders. AB - Sexual behavior over the past year of 32 outpatients with Bipolar disorder is compared to that of 44 Comparison patients that had never had an episode of affective illness. Subjects were outpatients treated with drugs and psychotherapy in routine office practice. Differences in sexual behavior between the two groups as a whole were minimal, but meaningful differences emerged when subgroups were compared. Compared to control men, Bipolar men had had more partners in the last year and were more likely to have had sex without condoms. Compared to Bipolar females, Bipolar males had more sex partners, had more sex with strangers, and were more likely to have engaged in homosexual behavior. Even so, some patients in the Comparison group also had engaged in risky sexual behavior. They had failed to use condoms and had had sex with strangers and prostitutes during the previous year. PMID- 27190985 TI - Reconstructing the Phylogeny of Capsosiphon fulvescens (Ulotrichales, Chlorophyta) from Korea Based on rbcL and 18S rDNA Sequences. AB - Capsosiphon fulvescens is a filamentous green algae in the class Ulvophyceae. It has been consumed as food with unique flavor and soft texture to treat stomach disorders and hangovers, and its economic value justifies studying its nutritional and potential therapeutic effects. In contrast to these applications, only a few taxonomic studies have been conducted on C. fulvescens. In particular, classification and phylogenetic relationships of the C. fulvescens below the order level are controversial. To determine its phylogenetic position in the class, we used rbcL and 18S rDNA sequences as molecular markers to construct phylogenetic trees. The amplified rbcL and 18S rDNA sequences from 4 C. fulvescens isolates (Jindo, Jangheung, Wando, and Koheung, Korea) were used for phylogenetic analysis by employing three different phylogenetic methods: neighbor joining (NJ), maximum parsimony (MP), and maximum likelihood (ML). The rbcL phylogenetic tree showed that all taxa in the order Ulvales were clustered as a monophyletic group and resolved the phylogenetic position of C. fulvescens in the order Ulotrichales. The significance of our study is that the 18S rDNA phylogenetic tree shows the detailed taxonomic position of C. fulvescens. In our result, C. fulvescens is inferred as a member of Ulotrichaceae, along with Urospora and Acrosiphonia. PMID- 27190987 TI - Efficiency Analysis of Direct Video-Assisted Thoracoscopic Surgery in Elderly Patients with Blunt Traumatic Hemothorax without an Initial Thoracostomy. AB - Hemothorax is common in elderly patients following blunt chest trauma. Traditionally, tube thoracostomy is the first choice for managing this complication. The goal of this study was to determine the benefits of this approach in elderly patients with and without an initial tube thoracostomy. Seventy-eight patients aged >65 years with blunt chest trauma and stable vital signs were included. All of them had more than 300 mL of hemothorax, indicating that a tube thoracostomy was necessary. The basic demographic data and clinical outcomes of patients with hemothorax who underwent direct video-assisted thoracoscopic surgery without a tube thoracostomy were compared with those who received an initial tube thoracostomy. Patients who did not receive a thoracostomy had lower posttrauma infection rates (28.6% versus 56.3%, P = 0.061) and a significantly shorter length of stay in the intensive care unit (3.13 versus 8.27, P = 0.029) and in the hospital (15.93 versus 23.17, P = 0.01) compared with those who received a thoracostomy. The clinical outcomes in the patients who received direct VATS were more favorable compared with those of the patients who did not receive direct VATS. PMID- 27190986 TI - The Serum Levels of the Soluble Factors sCD40L and CXCL1 Are Not Indicative of Endometriosis. AB - Endometriosis is a benign but troublesome gynecological condition, characterized by endometrial-like tissue outside the uterine cavity. Lately, the discovery and validation of noninvasive diagnostic biomarkers for endometriosis is one of the main priorities in the field. As the disease elicits a chronic inflammatory reaction, we focused our interest on two factors well known to be involved in inflammation and neoplastic processes, namely, soluble CD40 Ligand and CXCL1, and asked whether differences in the serum levels of sCD40L and CXCL1 in endometriosis patients versus controls can serve as noninvasive disease markers. A total of n = 60 women were included in the study, 31 endometriosis patients and 29 controls, and the serum levels of sCD40L and CXCL1 were measured by enzyme linked immunosorbent assay. Overall, there were no statistically significant differences in the levels of expression of both sCD40L and CXCL1 between patients and controls. This study adds useful clinical data showing that the serum levels of the soluble factors sCD40L and CXCL1 are not associated with endometriosis and are not suitable as biomarkers for disease diagnosis. However, we found a trend toward lower levels of sCD40L in the deep infiltrating endometriosis subgroup making it a potentially interesting target worth further investigation. PMID- 27190991 TI - Automatic Extraction of Appendix from Ultrasonography with Self-Organizing Map and Shape-Brightness Pattern Learning. AB - Accurate diagnosis of acute appendicitis is a difficult problem in practice especially when the patient is too young or women in pregnancy. In this paper, we propose a fully automatic appendix extractor from ultrasonography by applying a series of image processing algorithms and an unsupervised neural learning algorithm, self-organizing map. From the suggestions of clinical practitioners, we define four shape patterns of appendix and self-organizing map learns those patterns in pixel clustering phase. In the experiment designed to test the performance for those four frequently found shape patterns, our method is successful in 3 types (1 failure out of 45 cases) but leaves a question for one shape pattern (80% correct). PMID- 27190989 TI - Induction of Poly(ADP-ribose) Polymerase in Mouse Bone Marrow Stromal Cells Exposed to 900 MHz Radiofrequency Fields: Preliminary Observations. AB - Background. Several investigators have reported increased levels of poly(ADP ribose) polymerase-1 (PARP-1), a nuclear enzyme which plays an important role in the repair of damaged DNA, in cells exposed to extremely low dose ionizing radiation which does not cause measurable DNA damage. Objective. To examine whether exposure of the cells to nonionizing radiofrequency fields (RF) is capable of increasing messenger RNA of PARP-1 and its protein levels in mouse bone marrow stromal cells (BMSCs). Methods. BMSCs were exposed to 900 MHz RF at 120 MUW/cm(2) power intensity for 3 hours/day for 5 days. PARP-1 mRNA and its protein levels were examined at 0, 0.5, 1, 2, 4, 6, 8, and 10 hours after exposure using RT-PCR and Western blot analyses. Sham-exposed (SH) cells and those exposed to ionizing radiation were used as unexposed and positive control cells. Results. BMSCs exposed to RF showed significantly increased expression of PARP-1 mRNA and its protein levels after exposure to RF while such changes were not observed in SH-exposed cells. Conclusion. Nonionizing RF exposure is capable of inducing PARP-1. PMID- 27190988 TI - HSP27 Inhibits Homocysteine-Induced Endothelial Apoptosis by Modulation of ROS Production and Mitochondrial Caspase-Dependent Apoptotic Pathway. AB - Objectives. Elevated plasma homocysteine (Hcy) could lead to endothelial dysfunction and is viewed as an independent risk factor for atherosclerosis. Heat shock protein 27 (HSP27), a small heat shock protein, is reported to exert protective effect against atherosclerosis. This study aims to investigate the protective effect of HSP27 against Hcy-induced endothelial cell apoptosis in human umbilical vein endothelial cells (HUVECs) and to determine the underlying mechanisms. Methods. Apoptosis, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) of normal or HSP27-overexpressing HUVECs in the presence of Hcy were analyzed by flow cytometry. The mRNA and protein expression levels were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Results. We found that Hcy could induce cell apoptosis with corresponding decrease of nitric oxide (NO) level, increase of endothelin-1 (ET 1), intracellular adhesion molecule-1 (ICAM-1), vascular cellular adhesion molecule-1 (VCAM-1), and monocyte chemoattractant protein-1 (MCP-1) levels, elevation of ROS, and dissipation of MMP. In addition, HSP27 could protect the cell against Hcy-induced apoptosis and inhibit the effect of Hcy on HUVECs. Furthermore, HSP27 could increase the ratio of Bcl-2/Bax and inhibit caspase-3 activity. Conclusions. Therefore, we concluded that HSP27 played a protective role against Hcy-induced endothelial apoptosis through modulation of ROS production and the mitochondrial caspase-dependent apoptotic pathway. PMID- 27190990 TI - Phytochemical Composition and Antibacterial Activity of Hydroalcoholic Extracts of Pterospartum tridentatum and Mentha pulegium against Staphylococcus aureus Isolates. AB - Pterospartum tridentatum and Mentha pulegium are largely used in Portuguese folk medicine to treat several human disorders and inflammatory processes but without any consistent evidence for those beneficial pointed properties. Thus, the aim of the current work is to evaluate its benefits and phytochemicals related to those beneficial properties. A distinct polyphenol profile between P. tridentatum and M. pulegium was found. Taxifolin, myricetin, ginestin, ginestein, and ginestein derivatives, biochanin A-glucoside, and biochanin A were identified in P. tridentatum, whilst in M. pulegium the luteolin-7-rutinoside, diosmin, and apigenin and respective derivatives were most representative polyphenols. These variations had implications in the antiradical and antibacterial activity and the P. tridentatum exhibited the highest antibacterial activity against methicillin resistant and methicillin-sensitive Staphylococcus aureus MSSA, which was mainly dose-dependent. This antibacterial activity seems to be related to high content of flavonols, flavones, and isoflavones, which can act synergistically with each other against this type of bacteria. Our results showed consistent evidence that Pterospartum tridentatum and Mentha pulegium are an important reservoir of phytochemicals with antiradical activity and antibacterial capacity and thus they might be used in a preventive way or in a combined pharmaceutical and antibiotic therapy against pathogenic bacteria. PMID- 27190992 TI - The Occurrence of Genetic Alterations during the Progression of Breast Carcinoma. AB - The interrelationship among genetic variations between the developing process of carcinoma and the order of occurrence has not been completely understood. Interpreting the mechanisms of copy number variation (CNV) is absolutely necessary for understanding the etiology of genetic disorders. Oncogenetic tree is a special phylogenetic tree inferential pictorial representation of oncogenesis. In our present study, we constructed oncogenetic tree to imitate the occurrence of genetic and cytogenetic alterations in human breast cancer. The oncogenetic tree model was built on CNV of ErbB2, AKT2, KRAS, PIK3CA, PTEN, and CCND1 genes in 963 cases of tumors with sequencing and CNA data of human breast cancer from TCGA. Results from the oncogenetic tree model indicate that ErbB2 copy number variation is the frequent early event of human breast cancer. The oncogenetic tree model based on the phylogenetic tree is a type of mathematical model that may eventually provide a better way to understand the process of oncogenesis. PMID- 27190993 TI - Effects of Short-Term Physical Activity Interventions on Simple and Choice Response Times. AB - Objective. Response time (RT) is important for health and human performance and provides insight into cognitive processes. It deteriorates with age, is associated with chronic physical activity (PA), and improves with PA interventions. We investigated associations between the amount and type of PA undertaken and the rate of change in RT for low-active adults across the age range 18-63 yr. Methods. Insufficiently active adults were assigned to either a walking (n = 263) or higher-intensity (n = 380) exercise program conducted over 40 days. Active controls were also recruited (n = 135). Simple response time (SRT) and choice response time (CRT) were measured before and after the intervention and at 3-, 6-, and 12-month follow-up. Results. SRT and CRT slowed across the age range; however, habitually active participants at baseline had significantly faster CRT (p < 0.05). The interventions increased weekly PA with corresponding increases in physical fitness. These changes were mirrored in faster CRT across the study for both intervention groups (p < 0.05). No changes were found for SRT. Conclusions. Both PA interventions resulted in improvements in CRT among adults starting from a low activity base. These improvements were relatively rapid and occurred in both interventions despite large differences in exercise volume, type, and intensity. There were no effects on SRT in either intervention. PMID- 27190994 TI - Are Patients with Polycystic Ovarian Syndrome Ideal Candidates for Oocyte Donation? AB - Background. The use of donated oocytes for in vitro fertilization treatment in patients with ovarian failure is universally recognized. But would patients with polycystic ovarian syndrome (PCOS) be a good choice for egg donation programs? Objective. Comparing the pregnancy rates of egg receptors from donor patients diagnosed with PCOS to receptors from donors without PCOS. Design. Retrospective cohort study. Methods. A total of 234 patients who had undergone egg reception program were separated into two groups: Group I, receptors from PCOS donors (n = 36); Group II, receptors from donors without PCOS (n = 198). Medical records were reviewed and the fertilization, implantation, and pregnancy rates were calculated. Results. PCOS patients had an average of 3.23 more oocytes retrieved, but there were no differences in the number of mature oocytes that were used for donation between the groups. We also observed that the number of transferred embryos was also not significantly different, as well as the fertilization and implantation rates. The clinical pregnancy rates were not significantly different: 28% and 26% in Group I and Group II, respectively. Conclusions. Women with PCOS should not be excluded from egg donation programs. PMID- 27190995 TI - WWOX CNV-67048 Functions as a Risk Factor for Epithelial Ovarian Cancer in Chinese Women by Negatively Interacting with Oral Contraceptive Use. AB - Copy number variations (CNVs) have attracted increasing evidences to represent their roles as cancer susceptibility regulators. However, little is known about the role of CNV in epithelia ovarian cancer (EOC). Recently, the CNV-67048 of WW domain-containing oxidoreductase (WWOX) was reported to alter cancer risks. Considering that WWOX also plays a role in EOC, we hypothesized that the CNV 67048 was associated with EOC risk. In a case-control study of 549 EOC patients and 571 age (+/-5 years) matched cancer-free controls, we found that the low copy number of CNV-67048 (1-copy and 0-copy) conferred a significantly increased risk of EOC (OR = 1.346, 95% CI = 1.037-1.747) and it determined the risk by means of copy number-dependent dosage effect (P = 0.009). Data from TCGA also confirmed the abovementioned association as the frequency of low copies in EOC group was 3.68 times more than that in healthy group (P = 0.023). The CNV also negatively interacted with oral contraceptive use on EOC risk (P = 0.042). Functional analyses further showed a lower mRNA level of WWOX in tissues with the 0-copy or 1-copy than that in those with the 2-copy (P = 0.045). Our data suggested the CNV 67048 to be a risk factor of EOC in Chinese women. PMID- 27190996 TI - Prevalence of Diabetic Foot Disease in Patients with Diabetes Mellitus under Renal Replacement Therapy in Lleida, Spain. AB - Aim. To assess the prevalence of diabetic foot and other associated conditions in patients with diabetes mellitus under renal replacement in the region of Lleida, Spain. Methods. This was an observational, cross-sectional study of 92 dialysis treated diabetic patients. Besides a podiatric examination, we explored the presence of cardiovascular risk factors, late diabetes complications, including peripheral neuropathy, atherosclerotic disease, and peripheral artery disease. We assessed risk factors for foot ulceration and amputation by logistic regression. Results. Prevalent diabetic foot was found in 17.4% of patients, foot deformities were found in 54.3%, previous ulcer was found in 19.6%, and amputations were found in 16.3%; and 87% of them had some risk of suffering diabetic foot in the future. We observed a high prevalence of patients with peripheral neuropathy and peripheral artery disease (89.1% and 64.2%, resp.). Multivariable analysis identified diabetic retinopathy and advanced atherosclerotic disease (stenosing carotid plaques) as independent risk factors for foot ulceration (p = 0.004 and p = 0.023, resp.) and diabetic retinopathy also as an independent risk factor for lower-limb amputations (p = 0.013). Moreover, there was a temporal association between the initiation of dialysis and the incidence of amputations. Conclusion. Diabetic patients receiving dialysis therapy are at high risk of foot complications and should receive appropriate and intensive foot care. PMID- 27190997 TI - The Antitumor Effect of Gekko Sulfated Glycopeptide by Inhibiting bFGF-Induced Lymphangiogenesis. AB - Objective. To study the antilymphangiogenesis effect of Gekko Sulfated Glycopeptide (GSPP) on human lymphatic endothelial cells (hLECs). Methods. MTS was conducted to confirm the antiproliferation effect of GSPP on hLECs; flow cytometry was employed to detect hLECs cycle distribution; the antimigration effect of GSPP on hLECs was investigated by wound healing experiment and transwell experiment; tube formation assay was used to examine its inhibitory effect on the lymphangiogenesis; western blotting was conducted to detect the expression of extracellular signal-regulated kinase1/2 (Erk1/2) and p-Erk1/2 after GSPP and basic fibroblast growth factor (bFGF) treatment. Nude mice models were established to investigate the antitumor effect of GSPP in vivo. Decreased lymphangiogenesis caused by GSPP in vivo was verified by immunohistochemical staining. Results. In vitro, GSPP (10 MUg/mL, 100 MUg/mL) significantly inhibited bFGF-induced hLECs proliferation, migration, and tube-like structure formation (P < 0.05) and antagonized the phosphorylation activation of Erk1/2 induced by bFGF. In vivo, GSPP treatment (200 mg/kg/d) not only inhibited the growth of colon carcinoma, but also inhibited the tumor lymphangiogenesis. Conclusion. GSPP possesses the antitumor ability by inhibiting bFGF-inducing lymphangiogenesis in vitro and in vivo, which may further inhibit tumor lymphatic metastasis. PMID- 27190998 TI - Prostaglandin E Receptor Subtype 4 Signaling in the Heart: Role in Ischemia/Reperfusion Injury and Cardiac Hypertrophy. AB - Prostaglandin E2 (PGE2) is an endogenous lipid mediator, produced from the metabolism of arachidonic acids, upon the sequential actions of phospholipase A2, cyclooxygenases, and prostaglandin E synthases. The various biological functions governed by PGE2 are mediated through its four distinct prostaglandin E receptors (EPs), designated as EP1, EP2, EP3, and EP4, among which the EP4 receptor is the one most widely distributed in the heart. The availability of global or cardiac specific EP4 knockout mice and the development of selective EP4 agonists/antagonists have provided substantial evidence to support the role of EP4 receptor in the heart. However, like any good drama, activation of PGE2-EP4 signaling exerts both protective and detrimental effects in the ischemic heart disease. Thus, the primary object of this review is to provide a comprehensive overview of the current progress of the PGE2-EP4 signaling in ischemic heart diseases, including cardiac hypertrophy and myocardial ischemia/reperfusion injury. A better understanding of PGE2-EP4 signaling should promote the development of more effective therapeutic approaches to treat the ischemic heart diseases without triggering unwanted side effects. PMID- 27190999 TI - A Novel Chemically Modified Curcumin "Normalizes" Wound-Healing in Rats with Experimentally Induced Type I Diabetes: Initial Studies. AB - Introduction. Impaired wound-healing in diabetics can lead to life-threatening complications, such as limb amputation, associated in part with excessive matrix metalloproteinase- (MMP-) mediated degradation of collagen and other matrix constituents. In the current study, a novel triketonic chemically modified curcumin, CMC2.24, was tested for efficacy in healing of standardized skin wounds in streptozotocin-induced diabetic rats. Initially, CMC2.24 was daily applied topically at 1% or 3% concentrations or administered systemically (oral intubation; 30 mg/kg); controls received vehicle treatment only. Over 7 days, the diabetics exhibited impaired wound closure, assessed by gross and histologic measurements, compared to the nondiabetic controls. All drug treatments significantly improved wound closure with efficacy ratings as follows: 1% 2.24 > systemic 2.24 > 3% 2.24 with no effect on the severe hyperglycemia. In subsequent experiments, 1% CMC2.24 "normalized" wound-healing in the diabetics, whereas 1% curcumin was no more effective than 0.25% CMC2.24, and the latter remained 34% worse than normal. MMP-8 was increased 10-fold in the diabetic wounds and topically applied 1% (but not 0.25%) CMC2.24 significantly reduced this excessive collagenase-2; MMP-13/collagenase-3 did not show significant changes. Additional studies indicated efficacy of 1% CMC2.24 over more prolonged periods of time up to 30 days. PMID- 27191000 TI - Heart Rate Variability as Early Biomarker for the Evaluation of Diabetes Mellitus Progress. AB - According to the American Diabetes Association (ADA), the side effects of diabetes mellitus have recently increased the global health expenditure each year. Of these, the early diagnostic can contribute to the decrease on renal, cardiovascular, and nervous systems complications. However, the diagnostic criteria, which are commonly used, do not suggest the diabetes progress in the patient. In this study, the streptozotocin model in mice (cDM) was used as early diagnostic criterion to reduce the side effects related to the illness. The results showed some clinical signs similarly to five-year diabetes progress without renal injury, neuropathies, and cardiac neuropathy autonomic in the cDM model. On the other hand, the electrocardiogram was used to determine alterations in heart rate and heart rate variability (HRV), using the Poincare plot to quantify the HRV decrease in the cDM-model. Additionally, the SD1/SD2 ratio and ventricular arrhythmias showed increase without side effects of diabetes. Therefore, the use of HRV as an early biomarker contributes to evaluating diabetes mellitus complications from the diagnostic. PMID- 27191001 TI - Neuroprotective Activity of (-)-Epigallocatechin Gallate against Lipopolysaccharide-Mediated Cytotoxicity. AB - Lipopolysaccharide- (LPS-) mediated systemic inflammation plays a critical role in neurodegenerative diseases. The present study was conducted to evaluate the protective effects of epigallocatechin gallate (EGCG), the major component in green tea, on LPS-mediated inflammation and neurotoxicity. LPS treatment of macrophages induced expression of proinflammatory cytokines (TNF-alpha, IL-1beta, and IL-6). However, EGCG pretreatment of macrophages significantly inhibited LPS mediated induction of these cytokines. In addition, EGCG significantly diminished LPS-induced inflammatory cytokines in the peripheral mononuclear blood cells (PBMCs). Supernatant from EGCG-pretreated and LPS-activated macrophage cultures was found to be less cytotoxic to neurons than that from non-EGCG-pretreated and LPS-activated macrophage cultures. Furthermore, EGCG treatment of neurons could inhibit LPS-induced production of reactive oxygen species (ROS). Thus EGCG represents a potent and useful neuroprotective agent for inflammation-mediated neurological disorders. PMID- 27191003 TI - In Vivo Chemoprotective Activity of Bovine Dialyzable Leukocyte Extract in Mouse Bone Marrow Cells against Damage Induced by 5-Fluorouracil. AB - Chemotherapy treatments induce a number of side effects, such as leukopenia neutropenia, peripheral erythropenia, and thrombocytopenia, affecting the quality of life for cancer patients. 5-Fluorouracil (5-FU) is wieldy used as myeloablative model in mice. The bovine dialyzable leukocyte extract (bDLE) or IMMUNEPOTENT CRP(r) (ICRP) is an immunomodulatory compound that has antioxidants and anti-inflammatory effects. In order to investigate the chemoprotection effect of ICRP on bone marrow cells in 5-FU treated mice, total bone marrow (BM) cell count, bone marrow colony forming units-granulocyte/macrophage (CFU-GM), cell cycle, immunophenotypification, ROS/superoxide and Nrf2 by flow cytometry, and histological and hematological analyses were performed. Our results demonstrated that ICRP increased BM cell count and CFU-GM number, arrested BM cells in G0/G1 phase, increased the percentage of leukocyte, granulocytic, and erythroid populations, reduced ROS/superoxide formation and Nrf2 activation, and also improved hematological levels and weight gain in 5-FU treated mice. These results suggest that ICRP has a chemoprotective effect against 5-FU in BM cells that can be used in cancer patients. PMID- 27191004 TI - Identification of Bacterial and Viral Codetections With Mycoplasma pneumoniae Using the TaqMan Array Card in Patients Hospitalized With Community-Acquired Pneumonia. AB - Mycoplasma pneumoniae was detected in a number of patients with community acquired pneumonia in a recent prospective study. To assess whether other pathogens were also detected in these patients, TaqMan Array Cards were used to test 216 M pneumoniae-positive respiratory specimens for 25 additional viral and bacterial respiratory pathogens. It is interesting to note that 1 or more codetections, predominantly bacterial, were identified in approximately 60% of specimens, with codetections being more common in children. PMID- 27191005 TI - Peripheral Intravenous Catheter Placement Is an Underrecognized Source of Staphylococcus aureus Bloodstream Infection. AB - Few studies have focused on the risks of peripheral intravenous catheters (PIVs) as sources for Staphylococcus aureus bacteremia (SAB), a life-threatening complication. We identified 34 PIV-related infections (7.6%) in a cohort of 445 patients with SAB. Peripheral intravenous catheter-related SAB was associated with significantly longer bacteremia duration and thrombophlebitis at old PIV sites rather than current PIVs. PMID- 27191006 TI - Immunological Signaling During Herpes Simplex Virus-2 and Cytomegalovirus Vaginal Shedding After Initiation of Antiretroviral Treatment. AB - Vaginal proinflammatory cytokine expression during herpes virus reactivation was examined in human immunodeficiency virus-infected women before and after initiation of antiretroviral therapy (ART). Vaginal swabs were screened for levels of cytokines interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL 12p70, IL-13, tumor necrosis factor (TNF)-alpha, and interferon-gamma. The relative risk (RR) of herpes simplex virus-2 or cytomegalovirus (CMV) shedding being associated with cytokine levels above the median were estimated. Herpes simplex virus-2 shedding was significantly associated with higher levels of IL-6 (RR = 1.4, P = .003) and TNF-alpha (RR = 1.3, P = .010), whereas CMV shedding was associated with higher IL-6 (RR = 1.3, P = .006) and IL-2 (RR = 1.4, P = .01). The association of viral shedding with higher IL-6 levels suggests that herpes virus reactivation may be playing a role in immune activation after ART initiation. PMID- 27191007 TI - Acceptability of Rapid Point-of-Care Hepatitis C Tests Among People Who Inject Drugs and Utilize Syringe-Exchange Programs. AB - People who inject drugs may benefit from point-of-care hepatitis C virus (HCV) testing offered at syringe exchanges. We sought to understand whether this population would be willing to undergo rapid HCV testing. We found that there was broad support for rapid HCV testing, especially among younger people who inject drugs with high perceived risk. PMID- 27191002 TI - Posttranslational Modifications and the Immunogenicity of Biotherapeutics. AB - Whilst the amino acid sequence of a protein is determined by its gene sequence, the final structure and function are determined by posttranslational modifications (PTMs), including quality control (QC) in the endoplasmic reticulum (ER) and during passage through the Golgi apparatus. These processes are species and cell specific and challenge the biopharmaceutical industry when developing a production platform for the generation of recombinant biologic therapeutics. Proteins and glycoproteins are also subject to chemical modifications (CMs) both in vivo and in vitro. The individual is naturally tolerant to molecular forms of self-molecules but nonself variants can provoke an immune response with the generation of anti-drug antibodies (ADA); aggregated forms can exhibit enhanced immunogenicity and QC procedures are developed to avoid or remove them. Monoclonal antibody therapeutics (mAbs) are a special case because their purpose is to bind the target, with the formation of immune complexes (ICs), a particular form of aggregate. Such ICs may be removed by phagocytic cells that have antigen presenting capacity. These considerations may frustrate the possibility of ameliorating the immunogenicity of mAbs by rigorous exclusion of aggregates from drug product. Alternate strategies for inducing immunosuppression or tolerance are discussed. PMID- 27191008 TI - Preface to Special Topic: Invited Papers of the 3rd International Conference on Ultrafast Structural Dynamics. AB - The ability to visualize the real-time dynamics of atomic, magnetic, and electronic structure is widely recognized in many fields as a key element underpinning many important processes in chemistry, materials science, and biology. The need for an improved understanding of such processes becomes acute as energy conversion processes on fast time scales become increasingly relevant to problems in science and technology. This special issue, containing invited papers from participants at the 3rd International Conference on Ultrafast Structural Dynamics held June 10-12, 2015 in Zurich, Switzerland, discusses several recent developments in this area. PMID- 27191009 TI - Energy utilization in fluctuating biological energy converters. AB - We have argued previously [Szoke et al., FEBS Lett. 553, 18-20 (2003); Curr. Chem. Biol. 1, 53-57 (2007)] that energy utilization and evolution are emergent properties based on a small number of established laws of physics and chemistry. The relevant laws constitute a framework for biology on a level intermediate between quantum chemistry and cell biology. There are legitimate questions whether these concepts are valid at the mesoscopic level. Such systems fluctuate appreciably, so it is not clear what their efficiency is. Advances in fluctuation theorems allow the description of such systems on a molecular level. We attempt to clarify this topic and bridge the biochemical and physical descriptions of mesoscopic systems. PMID- 27191011 TI - Femtosecond infrared spectroscopy of channelrhodopsin-1 chromophore isomerization. AB - Vibrational dynamics of the retinal all-trans to 13-cis photoisomerization in channelrhodopsin-1 from Chlamydomonas augustae (CaChR1) was investigated by femtosecond visible pump mid-IR probe spectroscopy. After photoexcitation, the transient infrared absorption of C-C stretching modes was detected. The formation of the 13-cis photoproduct marker band at 1193 cm(-1) was observed within the time resolution of 0.3 ps. We estimated the photoisomerization yield to (60 +/- 6) %. We found additional time constants of (0.55 +/- 0.05) ps and (6 +/- 1) ps, assigned to cooling, and cooling processes with a back-reaction pathway. An additional bleaching band demonstrates the ground-state heterogeneity of retinal. PMID- 27191010 TI - Structural dynamics of a methionine gamma-lyase for calicheamicin biosynthesis: Rotation of the conserved tyrosine stacking with pyridoxal phosphate. AB - CalE6 from Micromonospora echinospora is a (pyridoxal 5' phosphate) PLP-dependent methionine gamma-lyase involved in the biosynthesis of calicheamicins. We report the crystal structure of a CalE6 2-(N-morpholino)ethanesulfonic acid complex showing ligand-induced rotation of Tyr100, which stacks with PLP, resembling the corresponding tyrosine rotation of true catalytic intermediates of CalE6 homologs. Elastic network modeling and crystallographic ensemble refinement reveal mobility of the N-terminal loop, which involves both tetrameric assembly and PLP binding. Modeling and comparative structural analysis of PLP-dependent enzymes involved in Cys/Met metabolism shine light on the functional implications of the intrinsic dynamic properties of CalE6 in catalysis and holoenzyme maturation. PMID- 27191012 TI - Femtosecond X-ray solution scattering reveals that bond formation mechanism of a gold trimer complex is independent of excitation wavelength. AB - The [Au(CN)2 (-)]3 trimer in water experiences a strong van der Waals interaction between the d(10) gold atoms due to large relativistic effect and can serve as an excellent model system to study the bond formation process in real time. The trimer in the ground state (S0) exists as a bent structure without the covalent bond between the gold atoms, and upon the laser excitation, one electron in the antibonding orbital goes to the bonding orbital, thereby inducing the formation of a covalent bond between gold atoms. This process has been studied by various time-resolved techniques, and most of the interpretation on the structure and dynamics converge except that the structure of the first intermediate (S1) has been debated due to different interpretations between femtosecond optical spectroscopy and femtosecond X-ray solution scattering. Recently, the excitation wavelength of 267 nm employed in our previous scattering experiment was suggested as the culprit for misinterpretation. Here, we revisited this issue by performing femtosecond X-ray solution scattering with 310 nm excitation and compared the results with our previous study employing 267 nm excitation. The data show that a linear S1 structure is formed within 500 fs regardless of excitation wavelength and the structural dynamics observed at both excitation wavelengths are identical to each other within experimental errors. PMID- 27191013 TI - Evaluation of Spontaneous Pneumothorax Surgeries: A 16-Year Experience in Japan. AB - Background. Video-assisted thoracoscopic surgery is the surgical procedure of choice for spontaneous pneumothorax due to its noninvasiveness and convenience. A higher recurrence rate with thoracoscopic bullectomy (TB) than that after traditional thoracotomy (TT) led us to adopt thoracoscopic double-loop ligation (TLL) as our standard procedure in 1998. This study compares the effectiveness and safety of these 3 operative procedures. Methods. Patients who underwent their first surgery for spontaneous pneumothorax at our hospital between January 1994 and December 2010 were included. Patients with a history of surgery for spontaneous pneumothorax, those with special clinical conditions such as lymphangioleiomyomatosis, or those with catamenial, traumatic, or iatrogenic pneumothorax were excluded. Results. A total of 777 males (14-91 years old; 814 pneumothorax sides), and 96 females (16-78 years old; 99 pneumothorax sides) were included in the study. TT was performed in 137 patients (143 sides), TB in 106 patients (112 sides), and TLL in 630 patients (658 sides). The postoperative recurrence rates were 3.5%, 16.1%, and 5.3% in the TT, TB, and TLL groups, respectively (p < 0.0001). Mean blood loss and operating time were lowest for TLL. Conclusions. The results suggest that TLL should be the surgical procedure of choice for spontaneous pneumothorax. PMID- 27191015 TI - Clinical round-up. PMID- 27191014 TI - Oversolubility in the microvicinity of solid-solution interfaces. AB - Water-solid interactions at the macroscopic level (beyond tens of nanometers) are often viewed as the coexistence of two bulk phases with a sharp interface in many areas spanning from biology to (geo)chemistry and various technological fields (membranes, microfluidics, coatings, etc.). Here we present experimental evidence indicating that such a view may be a significant oversimplification. High resolution infrared and Raman experiments were performed in a 60 * 20 MUm(2) quartz cavity, synthetically created and initially filled with demineralized water. The IR mapping (3 * 3 MUm(2) beam size) performed using the SOLEIL synchrotron radiation source displays two important features: (i) the presence of a dangling free-OH component, a signature of hydrophobic inner walls; (ii) a shift of the OH-stretching band which essentially makes the 3200 cm(-1) sub-band predominate over the usual main component at around 3400 cm(-1). Raman maps confirmed these signatures (though less marked than IR's) and afforded a refined spatial distribution of this interfacial signal. This spatial resolution, statistically treated, results in a puzzling image of a 1-3 MUm thick marked liquid layer along the entire liquid-solid interface. The common view is then challenged by this strong evidence that a MUm-thick layer analogous to an interphase forms at the solid-liquid interface. The thermodynamic counterpart of the vibrational shifts amounts to around +1 kJ mol(-1) at the interface with a rapidly decreasing signature towards the cavity centre, meaning that vicinal water may form a reactive layer, of micrometer thickness, expected to have an elevated melting point, a depressed boiling temperature, and enhanced solvent properties. PMID- 27191016 TI - Postpartum pain in relation with Personal Meaning Organization. AB - AIM: The aim of this study was to investigate the relationship between postpartum pain and personality considered as Personal Meaning Organization (PMO). Pain diseases, not related to organic disorders, frequently occur in postpartum and may lead to severe consequences for women and their functions of caregiving. Emotions are usually experienced in the body and their expression is strictly related to individual personality. Considering personality as a process, each symptom expresses a need to maintain the sense of oneness and historical continuity. METHODS: One-hundred and five women were enrolled from the Department of Obstetrics and Gynecology and after delivery they presented postpartum pain not related to organic diseases. Women filled out a general information questionnaire assessing age, employment, marital status, education level, parity, type of delivery, attendance to a prepartum course, week of gestation. Their personality, as PMO, was evaluated using the Mini Questionnaire of Personal Organization (MQPO). RESULTS: Controller PMO perceived more pain compared to the Principle Oriented PMO (95% CIs [-0.09, -1.98]; Wald Z=-2.28; P<0.02), slightly more than contextualized patients (95% CIs [-0.09, -1.15]; Wald Z=-1.81, P<0.06) and more than those with a Detached PMO (95% CIs [-0.09, -2.10]; Wald Z=-1.84, P<0.06). CONCLUSION: The results suggest a role of PMO in influencing the perception of postpartum pain and no relation with the other general information assessed, particularly, within the controller women group in which the experience of physical pain might be a way to represent a subjective discomfort. PMID- 27191017 TI - [Pneumonia: The urgent problem of 21st century medicine]. AB - The paper analyzes the systematic reviews and meta-analyses on the strategic issues of pneumonia, which have been published in the past 3 years. It discusses the prevalence and mortality rates of acquired pneumonia, hospital-acquired (nosocomial) pneumonia, healthcare-associated pneumonia, ventilator-associated pneumonia, and Mycoplasma pneumonia, and the specific features of their etiology, diagnosis, and treatment. A large number of investigations emphasize the relevance of this problem in current clinical practice. PMID- 27191018 TI - [Anemias in chronic obstructive pulmonary disease]. AB - According to different studies, anemia occurs in 8--33% of patients with chronic obstructive pulmonary disease (COPD). The paper describes the most important various causes of anemia in COPD, such as systemic inflammation and endocrine disorders, the use of some medications (theophylline, angiotensin-converting enzyme inhibitors), frequent COPD exacerbations, and long-term oxygen therapy. Lower hemoglobin levels in COPD patients are accompanied by increased shortness of breath, reduced exercise tolerance, and lower quality of life. Furthermore, some investigations have shown that anemia is an independent predictor of death in patients with COPD. In spite of the fact that anemia may be successfully in these patients, the evidence suggesting the importance of its impact on the prognosis of COPD is limited. PMID- 27191021 TI - Oncogene panels: a window into the individuality of cancers. PMID- 27191019 TI - [Possible side effects of drugs in elderly patients with chronic obstructive pulmonary disease and comorbidity]. AB - the papers gives data on the positive effects and adverse reactions of drugs used to treat chronic obstructive pulmonary disease (COPD) and its comorbidity, first of all cardiovascular disease. The authors present alternative points of views based on both the data available in the literature and their findings. they propose to modify pharmacotherapy for COPD in the presence of comorbidity in patients of old age groups. PMID- 27191022 TI - Developing blood biomarker tests for the detection of cancer. PMID- 27191023 TI - IMPROVING QUALITY OF THE ETHIOPIAN MEDICAL JOURNAL: CURRENT CHALLENGES TO CHANGING THE TIDE. PMID- 27191024 TI - COMMON GENOTYPES AND TREATMENT OUTCOMES OF HCV INFECTION AMONG ETHIOPIAN PATIENTS: A PROSPECTIVE STUDY. AB - BACKGROUND: The treatment response of HCV infection is dependent on genotype and stage of the disease. However, genotype pattern and treatment outcomes of HCV infection among Ethiopian patients has not been studied so far. OBJECTIVES: To evaluate the common HCV genotypes and treatment outcomes among Ethiopian adult patients. METHOD: Adult patients aged 18 and above with HCV infection referred from various regions of the country were included in the study after written informed consent. As there was no free or insurance coverage for treatment of HCV infection in the country, those who could afford to pay for treatment with PEG Interferon and Ribavirin were recruited during January 1, 2008 through December 31,2013 at United Vision, Adera. Old Airport, and Mexico referral higher clinics in Addis Ababa. Patients with decompensated cirrhosis and pregnant ladies were excluded from the study. The patients were counseled on treatment options, cost, treatment outcomes, adverse drug effects, and possible complications. Data were collected on demographic features, clinical characteristics, viral genotypes, and treatment outcomes during follow up visits until six months after completion of recommended standard treatment. Data were analyzed using SPSS software. RESULTS: A total of 200 adults with chronic HCV infection were treated with PEG-Interferon and Ribavirin (for 24 or 48 weeks according to the genotypes) during the study period. Of the 200 patients enrolled in the study, 120 (60%) were male, 90% were from Addis Ababa, and the median age was 48 years. Sixty per cent of the patients were infected with genotype 4,17% with genotype 1, 13.5% with genotype 2 and 9.5% with genotype 3. Eighty percent of the patients had end of treatment response; of these, 74.4% had undetectable HCV RNA at 6th month after end of treatment. The end of treatment response was noted to be close to 90% for patients with HCV genotypes 2 and.3 infections. CONCLUSION: This study indicates that genotype 4 is the prevalent HCV genotype followed by 1, 2, and 3 among Ethiopian patients. Treatment with interferon and ribavirin was well tolerated and provided a very good response. PMID- 27191025 TI - PATTERNS AND SEASONAL VARIATION OF INTUSSUSCEPTION IN CHILDREN: A RETROSPECTIVE ANALYSIS OF CASES OPERATED IN A TERTIARY HOSPITAL IN ETHIOPIA. AB - BACKGROUND: Intussusception is one of the frequent causes of bowel obstruction in infants and toddlers (1). It involves invagination of a portion of intestine into another(2-4). The peak age of occurrence is between the age of 4 and 8 months. The aim of this study is to review the pattern of clinical presentation and seasonal variation of intussusception in our hospital, and to analyze the mode and outcomes of treatment. PATIENTS AND METHODS: This is a four-year retrospective study of children aged 13 years and below who were admitted and treated for intussusception between January 2011 and December 2014 at the pediatric surgery unit of Tikur Anbesa Specialized Hospital (TAH) in Ethiopia. Information on the patients' demographic characteristics, clinical presentation, and month of occurrence as well as the operative findings and outcome were obtained from the pediatric surgery unit record book, patient charts, and the operating theatre registry. RESULTS: One hundred and thirty six cases of intussusception were admitted to TAH, Addis Ababa over a four year period, of which 130 charts were retrieved and analyzed. Males dominated in the series. Age distribution showed that 59.2% of the cases were <= one year old, and 77.7 % were <= two years old. Abdominal pain, vomiting, bloody mucoid diarrhea and a mass palpated abdominally and/or rectally were the most common modes of presentations, with the classic triad of abdominal pain, vomiting and bloody mucoid diarrhea occurring in nearly two third of cases. The highest peak of presentation was in the month of June with 18 (13.9%) cases. The mean duration of symptoms before presentation to our hospital was 5.2 days with a range of 1-21 days. Intraoperatively, it was found that ileocolic intussusception was the most common type. Simple reduction without bowel resection was possible in 70.8% of cases. There were 44 (33.9 %) complications, wound site infection being the most common occurring in 20 (15.4%) cases and there were 6 deaths. CONCLUSION: Intussusception was more common in the wet season. There was delayed presentation with a higher rate of operative management and bowel resection. The mortality rate has decreased significantly compared with a previous study from this institution. PMID- 27191026 TI - OPEN WINDOW THORACOSTOMY, STILL AN OPTION IN THE MANAGEMENT OF CHRONIC EMPYEMA: EXPERIENCE FROM AYDER REFERRAL HOSPITAL. AB - OBJECTIVE: Chronic empyema is a serious problem and is often difficult to manage. Its incidence has dropped worldwide, but continues to pose health problems in low and middle income countries. This study has been conducted to assess the outcome of open thoracic window in patients with neglected chronic thoracic empyemain Ethiopian patients. METHODS: A six-year (June 2008 to October 2014) retrospective study was conducted on thirty five patients (ten females and twenty five males, age ranging from 30-70 years). Open window thoracostomy was performed on these patients for chronic empyema with residual lung tissue and with or without bronchopleural fistula who failed to respond to the conventional methods of treatment. RESULTS: The etiology was primary empyema in 16 patients, post traumatic in 12 patients, and post-thoracotomy in seven patients. Spontaneous closure was achieved in 12 patients; simple closure was done on 18 patients; and closure with muscle flap in five patients. In all patients, the cavity cleared from secretions in two to three weeks and the residual space narrowed in seven to nine months. All patients gained weight following the surgery. CONCLUSION: Our result has revealed that open thoracic window is still an alternative method for the treatment of chronic empyema when the conventional method of treatment fails. PMID- 27191027 TI - HEMATOLOGICAL AND LIPID PROFILES OF BLOOD DONORS AT RED CROSS CENTER IN ADDIS ABABA. AB - BACKGROUND: Physiological range of clinically important hematological laboratory values and lipid profiles of healthy population in Ethiopia is not well assessed. OBJECTIVE: to determine hematologic and lipid profiles of healthy blood donors in Addis Ababa. METHODS: Red Cross Society located in Addis Ababa was selected as a study area. 336 donors; age range between 18-58 years participated. Venous blood sample was collected by tube containing Ehtylenediaminetetraaceticacid tri potassium (EDTA) for hematology test and sterile tube for lipid test. After centrifugation serum was extracted for lipid test and transported to St. Pauls's Millennium Medical College (SPHMMC) within 5-8hrs of sample collection. IBM.SPSS version 21 was used for data analysis, statistical significance was set at P< 0.05 and 95% CL was accepted. RESULTS: Red blood cell count, mean corpuscular volume, platelet count and triglyceride level were significantly higher in the present study than the reference range. RBC indices, white blood cell, Hemoglobin, hematocrit, high density lipoprotein, low density lipoprotein and total cholesterol were higher in the reference range used in clinical practice. Significantly higher red blood count (p = 0.000), Hg (p = 0.000), Hematocrit (p = 0.000) and mean corpuscular hemoglobin concentration (p = 0.009) were observed in the male. Significantly higher platelet count and high density lipoprotein were observed among females (p = 0.001 and p = 0.001 respectively). No significant change in hematological laboratory values and lipid profiles was seen across age groups. CONCLUSION: It is evident from this study that hematological and lipid variables obtained were statistically significantly different from the reference range currently used in clinical practice. PMID- 27191028 TI - VISCERAL LEISHMANIASIS FROM AN AREA PREVIOUSLY NOT KNOWN TO BE ENDEMIC; DANGUR, BENSHANGUL-GUMUZ, REGIONAL STATE, NORTHWEST ETHIOPIA: A CASE REPORT. AB - Visceral leishmaniasis (VL) is a ftial and growing public health problem in Ethiopia. VL is recently reported outside the major endemic foci, the lowlands in the northwest and the Omo and Abaroba-plain, Segen and Woito valleys in the southwest. Here, we report a visceral leishmaniasis case from Benishangul-Gumuz Regional state near the Guba area. The patient had no history of travel to known VL endemic areas. The patient is a temporary farm laborer from West Go'jam Zone, Wanbermna District in Amhara Regional State. While in Benishangul-Gumuz, the patient was diagnosed with prolonged and intermittentfever, epistaxis, splenomegaly, skin pallor, diarrhea, cough and oedema. Laboratory diagnosis results showed that he had marked leucopenia, thrombocytopenia and anemia. The patient was suspected of having VL and checked with rK39 immunochromnatography and direct agglutination tests which were positive for anti leishmanial antibodies. After getting full dose of sodium stibogluconate as per the national visceral leishmaniasis treatment guideline, was clinically cured. As the area in Benshangul-Gumuz where this patient contracted visceral leishmaniasis is under social and ecological transformation with large scale projects attracting huge influx of temporary laborers and settlers, due attention is needed with respect to introduction or emergence of VL transmission. PMID- 27191029 TI - A RARE CASE OF HYDATID CYST DISEASE OF THE BREAST: A CASE REPORT AND REVIEW OF LITERATURE. AB - Hydatid cyst of the breast is extremely rare even in endemic areas and it only accounts for 0.27% of all hydatid cyst disease cases. It can either be a primary site or part of a disseminated hydatidosis. Surgery remains to be a treatment of choice. Only few reports are published in the literatures and most of the reported cases have been diagnosed postoperatively as it is not easy to reach at a definitive diagnosis with clinical examination and radiological investigations only. This is a case of an isolated hydatid cyst of breast in an 18-year old woman from the Amhara region, Ethiopia. She presented with left breast painless lump of 5 years duration and a correct pre-operative diagnosed was made by fine needle aspiration cytology, then confirmed after surgery. We believe this disease should be included in the differential diagnosis of benign breast lumps especially in endemic areas. PMID- 27191030 TI - Corrections. AB - [This corrects the article on p. E1 in vol. 104, PMID: 26807062.]. PMID- 27191031 TI - Enriching Photoelectrons via Three Transition Channels in Amino-Conjugated Carbon Quantum Dots to Boost Photocatalytic Hydrogen Generation. AB - Well-steered transport of photogenerated carriers in optoelectronic systems underlies many emerging solar conversion technologies, yet assessing the charge transition route in nanomaterials remains a challenge. Herein, we combine the photoinduced absorption, emission, and excitation properties in high luminescent carbon quantum dots (CQDs) with an amino-modified surface to identify the existence of three photoelectron transition channels, that is, near-band-edge transition, multiphoton active transition in CQDs, and transfer from amino groups to CQDs, and together they contribute to strong blue photoluminescence (PL) independent of the excitation wavelength. Moreover, the enriching electron reservoir via these three channels was demonstrated in a holes cleaning environment to efficiently trigger water splitting into hydrogen with excellent stability and recyclability. PMID- 27191032 TI - Pharmacological treatment of eosinophilic gastrointestinal disorders. AB - INTRODUCTION: Eosinophilic gastrointestinal disorders (EGIDs) are increasingly prevalent chronic inflammatory diseases characterized by eosinophilic infiltration of the gastrointestinal (GI) tract, in the absence of other known causes of eosinophilia. AREAS COVERED: Clinical management of EGIDs is challenging, as there are currently limited therapeutic options available. The most common EGID is eosinophilic esophagitis (EoE), and rarer forms are eosinophilic gastritis, eosinophilic gastroenteritis, and eosinophilic colitis. Clinical presentation depends on the affected GI site. Recently duodenal eosinophilia has been recognized to commonly be present in patients with functional dyspepsia. This review will provide an overview of the pathogenesis and therapeutic management of EGIDs, with particular focus on the pharmacological strategies for these conditions. Expert commentary: Despite the considerable progress made in understanding the pathogenesis of EGIDs, there is still an urgent need for the development of specific and effective therapeutic approaches. Therapeutic management protocols are required that are based on rigorous clinical investigation in large prospective controlled trials to better understand the risks, benefits and limitations of each therapy. More well-defined and consistent end-points are also required to assess treatment outcomes, as there has been variability between patient reported outcomes, clinical outcomes, and histological outcomes in the studies to date. PMID- 27191033 TI - Measurement of Multiple Vitamin K Forms in Processed and Fresh-Cut Pork Products in the U.S. Food Supply. AB - Vitamin K food composition data have historically been limited to plant-based phylloquinone (vitamin K1). The purpose of this study was to expand analysis of vitamin K to animal products and to measure phylloquinone and 10 forms of menaquinones (vitamin K2) in processed and fresh-cut pork products. Nationally representative samples of processed pork products (n = 28) were obtained through USDA's National Food and Nutrition Analysis Program, and fresh pork (six cuts; n = 5 per cut) and bacon (n = 4) were purchased from local retail outlets. All samples were analyzed by high-performance liquid chromatography (phylloquinone and menaquinone-4) and atmospheric-pressure chemical ionization-liquid chromatography-mass spectrometry (menaquinone-5 to menaquinone-13). Although low in phylloquinone (<2.1 +/- 0.5 MUg of phylloquinone per 100 g), all processed pork products and fresh pork cuts contained menaquinone-4, menaquinone-10, and menaquinone-11 (range: [35.1 +/- 11.0]-[534 +/- 89.0] MUg of menaquinones per 100 g). The total menaquinone contents of processed pork products were correlated with fat contents (r = 0.935). In summary, processed and fresh-cut pork products are a rich dietary source of menaquinones that are currently unaccounted for in assessment of vitamin K in the food supply. PMID- 27191034 TI - Hepatoprotective effect of trans-Chalcone on experimentally induced hepatic injury in rats: inhibition of hepatic inflammation and fibrosis. AB - The current study investigated the hepatoprotective effect of trans-Chalcone in carbon tetrachloride (CCl4) and paracetamol (PCM) induced liver damage in rats. Administration of CCl4 and PCM (1 mL/kg, i.p., 3 days, and 2 g/kg, p.o., single dose, respectively) produced hepatic injury. Ponderal changes (percent change in body mass and relative liver mass) and biochemical parameters (serum ALT, AST, ALP, bilirubin) were estimated. The markers of oxidative and nitrosative stress (TBARS, reduced GSH, nitrite and nitrate), hepatic fibrosis (TGF-beta1, collagen content), hepatic inflammation (TNF-alpha), and histopathological study were evaluated. trans-Chalcone (5, 10, and 20 mg/kg, i.p.) was found to be beneficial as demonstrated by significant reversal of liver histology by perceptible reduction of inflammatory cell infiltration with regenerative changes in hepatocytes. Improvement in percent change in body mass and significant reduction in relative liver mass were observed. Marked reduction in serum levels of ALT, AST, ALP, and bilirubin were noted. Decreases in TBARS and nitrites and nitrates and increases in reduced GSH levels were noted. Hepatic fibrosis and inflammation were significantly decreased. The findings indicate a novel hepatoprotective role for trans-Chalcone by improving hepatic injury by possible actions such as anti oxidant, anti-nitrosative, anti-fibrotic, and anti-inflammatory. Hence, it can be used as promising hepatoprotective agent. PMID- 27191036 TI - Manganese(II)/Picolinic Acid Catalyst System for Epoxidation of Olefins. AB - An in situ generated catalyst system based on Mn(CF3SO3)2, picolinic acid, and peracetic acid converts an extensive scope of olefins to their epoxides at 0 degrees C in <5 min, with remarkable oxidant efficiency and no evidence of radical behavior. Competition experiments indicate an electrophilic active oxidant, proposed to be a high-valent Mn = O species. Ligand exploration suggests a general ligand sphere motif contributes to effective oxidation. The method is underscored by its simplicity and use of inexpensive reagents to quickly access high value-added products. PMID- 27191035 TI - Shigella Antimicrobial Drug Resistance Mechanisms, 2004-2014. AB - To determine antimicrobial drug resistance mechanisms of Shigella spp., we analyzed 344 isolates collected in Switzerland during 2004-2014. Overall, 78.5% of isolates were multidrug resistant; 10.5% were ciprofloxacin resistant; and 2% harbored mph(A), a plasmid-mediated gene that confers reduced susceptibility to azithromycin, a last-resort antimicrobial agent for shigellosis. PMID- 27191037 TI - Relocation and Hair Cortisol Concentrations in New Zealand White Rabbits. AB - To investigate how long relocation modified hair cortisol concentrations in New Zealand white rabbits, 19 rabbits were subjected to a change in their breeding facility at the beginning of the trial and then were kept under stable environmental conditions. Hair samples were collected at the time of arrival to the nonhuman animal facility and at 40-day intervals from the same skin area for up to 440 days after the animals' arrival to the facility. A period effect on the hair cortisol concentration was found (p < .01). The transfer of the rabbits to the new facility might have induced an increase in the hypothalamic-pituitary adrenal axis activity (p < .01). A second increase in hair cortisol concentration (p < .01) occurred at 320 days, after a change of personnel at the facility that occurred at 280 days, which was the only environmental change. The relocation of rabbits to the facility resulted in a stress response leading to elevated cortisol levels. The effect of relocation on mean cortisol concentrations was exhausted within 120 days when all environmental factors were kept stable. PMID- 27191039 TI - CoPc 2D and 1D Arrangement on a Ferromagnetic Surface. AB - We investigated the growth and electronic properties of Co-phthalocyanine (CoPc) molecule deposited on iron film with different structures (pseudomorph-fcc and bcc) and on iron nanowires by scanning tunnelling microscopy and X-ray absorption spectroscopy (XAS). CoPc molecules self-assemble in a two-dimensional (2D) arrangement with the molecular plane parallel to the iron surfaces, and the local order is lost after the first layer. The molecule-ferromagnet interaction causes the broadening of Co and N unoccupied molecular states as well as different electronic distribution of N states as a function of the atomic structure of iron surface. The ferromagnetic coupling between the molecule and the iron film is dominated by the electronic interaction between Co and the first Fe layer. CoPc 2D arrangement turns into 1D by using as a template the iron nanowire grown on a facet surface of oxidized Cu(332) surface. CoPc molecules interact weakly with the iron nanowires manifesting a substantial Co 3dz spectral feature in XAS spectrum and the possibility of a magnetic interaction between Co moment and iron nanowires. Both CoPc 2D and 1D arrangements can open up new interesting scenarios to tune the magnetic properties of hybrid interfaces involving metallorganic molecules. PMID- 27191038 TI - Middle East Respiratory Syndrome Coronavirus Transmission in Extended Family, Saudi Arabia, 2014. AB - Risk factors for human-to-human transmission of Middle East respiratory syndrome coronavirus (MERS-CoV) are largely unknown. After MERS-CoV infections occurred in an extended family in Saudi Arabia in 2014, relatives were tested by using real time reverse transcription PCR (rRT-PCR) and serologic methods. Among 79 relatives, 19 (24%) were MERS-CoV positive; 11 were hospitalized, and 2 died. Eleven (58%) tested positive by rRT-PCR; 8 (42%) tested negative by rRT-PCR but positive by serology. Compared with MERS-CoV-negative adult relatives, MERS-CoV positive adult relatives were older and more likely to be male and to have chronic medical conditions. Risk factors for household transmission included sleeping in an index patient's room and touching respiratory secretions from an index patient. Casual contact and simple proximity were not associated with transmission. Serology was more sensitive than standard rRT-PCR for identifying infected relatives, highlighting the value of including serology in future investigations. PMID- 27191040 TI - Next-Generation Sequencing of Mycobacterium tuberculosis. PMID- 27191041 TI - Sudden fetal death due to dualism of the sino-atrial node. AB - First, we report a sudden fetal death at 33(+3)weeks due to sino-atrial node dualism. The female stillborn was delivered by induced labor. The postmortem examination of the cardiac conduction system revealed a dualism of the sino atrial node, associated with fragmentation of the atrio-ventricular node and His bundle. These abnormalities of the cardiac conduction system represent the morphological substrate for the development of malignant arrhythmias. In particular, the dualism of the sino-atrial node can cause the dissociation of the longitudinal nodal impulse into two distinct ways of different pulse generation, resulting in supraventricular tachyarrhythmias. This observation suggests new avenues of research on the pathogenesis of the sudden unexpected fetal death. Moreover, our findings confirm the need for an accurate postmortem examination, including serial sectioning of the cardiac conduction system, in every case of unexplained fetal death, following standardized autoptic protocols. PMID- 27191042 TI - Vitamin D and autoimmunity. AB - OBJECTIVES: To review and evaluate the role of vitamin D in autoimmune diseases based on current studies. METHOD: We searched PubMed using keywords such as 'vitamin D', 'autoimmune disease', and 'autoimmunity'. We compiled and reviewed various studies including prospective cohorts, cross-sectional studies, longitudinal evaluations, genetic studies, and experimental models that investigated the role of vitamin D in autoimmune diseases. RESULTS: There is evidence based on these various studies that several key autoimmune diseases are modulated by vitamin D. These diseases include, but are not limited to, multiple sclerosis (MS), scleroderma or systemic sclerosis (SSc), autoimmune thyroid diseases, rheumatoid arthritis (RA), and primary biliary cirrhosis (PBC). CONCLUSIONS: Although there is evidence for vitamin D as a factor in the pathophysiology of autoimmune diseases, the mechanism for this association has yet to be elucidated. Additional data are needed to corroborate these findings. PMID- 27191044 TI - Elevated irisin and alanine aminotransferase levels in hypothyroidism: role of oxidative stress? PMID- 27191043 TI - Autophagy in cardiac metabolic control: Novel mechanisms for cardiovascular disorders. AB - As an extensively studied quality control system, autophagy is responsible for clearance of dysfunctional organelles and damaged marcomolecules in cells. In addition to its biological recycling function, autophagy plays a significant role in the pathogenesis of metabolic syndromes such as obesity and diabetes. In particular, metabolic disorders contribute to cardiovascular disease development. As energy required to maintain cardiac cells functional is immense, disturbances in the balance between anabolic and catabolic metabolism possibly contribute to cardiovascular disorders. Therefore, an urgent need to expand our knowledge on the role of autophagy on the metabolic regulation of hearts emerges. In this review, the potential relationship between autophagic activity and cardiac metabolism is explored and we also discuss how dysregulated autophagy leads to severe cardiac disorders from the perspective of metabolic control. PMID- 27191045 TI - Biomarkers in diabetic kidney disease: good use and pitfalls. PMID- 27191046 TI - Evaluation of creatinine-based and cystatin C-based equations for estimation of glomerular filtration rate in type 1 diabetic patients. AB - Objective Several formulas based in different biomarkers may be used to estimate glomerular filtration rate (GRF). However, all of them have some limitations, and it is very important to evaluate their performances in different groups of patients. Therefore, we compared GFR, as estimated by creatinine-based and cystatin C-based equations, according to albuminuria, in type 1 diabetes (T1DM), in an observational case-control study. Subjects and methods T1DM patients were classified according to albuminuria: normoalbuminuric (n = 63), microalbuminuric (n = 30), macroalbuminuric (n = 32). GFR was calculated using creatinine-based and cystatin C-based (aMDRD, CKD-EPIcr, CKD-EPIcys, MacIsaac, Tan and CKD EPIcrcys) equations. Spearman Correlation was used to evaluate the correlation of GFR estimated by the formulas with albuminuria. ROC curves were constructed to compare AUCs of GFR estimated by equations, in reference to macroalbuminuria. Sensibility, specificity and accuracy were calculated for a cut-off < 60 mL/min/1.73 m2. Results GFR estimated by creatinine-based and cystatin C-based equations significantly differed among normoalbuminuric, microalbuminuric and macroalbuminuric patients. Spearman correlation and AUCs of GFR estimated by creatinine-based and cystatin C-based formulas were very similar to each other, though cystatin C-based equations presented better correlation with albuminuria and higher AUCs than the creatinine-based ones, and the best accuracy to detect macroalbuminuric patients. Conclusion Although GFR estimated by all creatinine based and cystatin C-based equations permitted the differentiation between T1DM patients, according to albuminuria, cystatin C-based equations presented best accuracy to detect macroalbuminuria in T1DM patients and should be considered in the clinical routine in order to increase the possibility of early diagnostic of chronic renal disease. PMID- 27191047 TI - Effects of excess maternal thyroxin on the bones of rat offspring from birth to the post-weaning period. AB - Objective To evaluate, in rat offspring, bone changes induced by excess maternal thyroxin during pregnancy and lactation, and to assess the reversibility of these changes after weaning. Material and methods Twenty Wistar rats were distributed in two groups, hyperthyroid and control, that were treated daily with L-thyroxin (50 mcg/animal) and placebo, respectively. The treatment was initiated seven days before mating and continued throughout pregnancy and lactation. From every female of each of the two groups, two offspring were euthanized after birth, two at 21 days of age (weaning), and two at 42 days of age (21 days after weaning). In newborns, the length of pelvic and thoracic limbs were measured, and in the other animals, the length and width of the femur and humerus were measured. Bones were dissected, decalcified, embedded in paraffin, and analyzed histomorphometrically. Results Excess maternal thyroxin significantly reduced the length of the pelvic limb in neonates. In 21-day-old individuals, excess maternal thyroxine reduced the length and the width of the femur and the humerus. It also increased thickness of the epiphyseal plate and the percentage of trabecular bone tissue. In 42-day-old individuals, there were no significant differences between groups in relation to the parameters evaluated in the previous periods. Conclusion Excess maternal thyroxine reduced growth in suckling rats both at birth and at weaning, and it also increased the percentage of trabecular bone tissue in 21-day old animals. These changes, however, were reversible at 42 days, i.e., 21 days after weaning. Arch Endocrinol Metab. 2016;60(2):130-7. PMID- 27191048 TI - Validation of HOMA-IR in a model of insulin-resistance induced by a high-fat diet in Wistar rats. AB - Objective The present study aimed to validate homeostasis model assessment of insulin resistance (HOMA-IR) in relation to the insulin tolerance test (ITT) in a model of insulin-resistance in Wistar rats induced by a 19-week high-fat diet. Materials and methods A total of 30 male Wistar rats weighing 200-300 g were allocated into a high-fat diet group (HFD) (55% fat-enriched chow, ad lib, n = 15) and a standard-diet group (CD) standard chow, ad lib, n = 15), for 19 weeks. ITT was determined at baseline and in the 19th week. HOMA-IR was determined between the 18-19th week in three different days and the mean was considered for analysis. Area under the curve (AUC-ITT) of the blood glucose excursion along 120 minutes after intra-peritoneal insulin injection was determined and correlated with the corresponding fasting values for HOMA-IR. Results AUC-ITT and HOMA-IR were significantly greater after 19th week in HFD compared to CD (p < 0.001 for both). AUC-OGTT was also higher in HFD rats (p = 0.003). HOMA-IR was strongly correlated (Pearson's) with AUC-ITT r = 0.637; p < 0.0001. ROC curves of HOMA-IR and AUC-ITT showed similar sensitivity and specificity. Conclusion HOMA-IR is a valid measure to determine insulin-resistance in Wistar rats. Arch Endocrinol Metab. 2016;60(2):138-42. PMID- 27191049 TI - Screening for asymptomatic coronary artery disease in patients with type 2 diabetes mellitus. AB - Diabetes is a very frequent disease and it is estimated that its prevalence will continuously increase during the next two decades. The arteriosclerotic process in diabetic patients progresses earlier and more diffusely, and it is more accelerated in the diabetic patient than in the overall population. In diabetic subjects, acute myocardial infarction (AMI) and stroke are the leading causes of death, but the presence of arterial disease is not always detected before the development of the acute arterial event. Several times, AMI is asymptomatic or present nonspecific symptoms, and it is the initial form of presentation of coronary artery disease causing an important delay in initiating cardiovascular treatment in these patients. The purpose of this review article is to discuss how to screen and early diagnose the presence of coronary artery disease in asymptomatic diabetic patients, based on new available diagnostic resources. Currently, the most recommended technique used for screening coronary artery disease in these patients is myocardial perfusion scintigraphy or stress echocardiography because of greater sensitivity and specificity in relation to the exercise test. However, technological advances have enabled the development of new imaging diagnostic methods that are less invasive than conventional coronary angiography, and which gradually gain importance in the diagnosis of coronary artery disease as they show higher effectiveness with lower invasiveness and risk. Arch Endocrinol Metab. 2016;60(2):143-51. PMID- 27191051 TI - [In Process Citation]. PMID- 27191050 TI - Central precocious puberty: revisiting the diagnosis and therapeutic management. AB - Clinical and laboratory diagnosis and treatment of central precocious puberty (CPP) remain challenging due to lack of standardization. The aim of this revision was to address the diagnostic and therapeutic features of CPP in Brazil based on relevant international literature and availability of the existing therapies in the country. The diagnosis of CPP is based mainly on clinical and biochemical parameters, and a period of follow-up is desirable to define the "progressive" form of sexual precocity. This occurs due to the broad spectrum of pubertal development, including isolated premature thelarche, constitutional growth and puberty acceleration, progressive and nonprogressive CPP, and early puberty. Measurement of basal and stimulated LH levels remains challenging, considering that the levels are not always in the pubertal range at baseline, short-acting GnRH is not readily available in Brazil, and the cutoff values differ according to the laboratory assay. When CPP is suspected but basal LH values are at prepubertal range, a stimulation test with short-acting or long-acting monthly GnRH is a diagnostic option. In Brazil, the treatment of choice for progressive CPP and early puberty is a long-acting GnRH analog (GnRHa) administered once a month or every 3 months. In Brazil, formulations of GnRHa (leuprorelin and triptorelin) are available and commonly administered, including 1-month depot leuprorelin 3.75 mg and 7.5 mg, 1-month depot triptorelin 3.75 mg, and 3-month depot leuprorelin 11.25 mg. Monthly or 3-month depot GnRHa are effective and safe to treat CPP. Arch Endocrinol Metab. 2016;60(2):163-72. PMID- 27191052 TI - In vitro assessment of potential intestinal absorption of some phenolic families and carboxylic acids from commercial instant coffee samples. AB - Coffee is one of the most consumed beverages in the world, being a source of bioactive compounds as well as flavors. Hydroxycinnamic acids, flavonols, and carboxylic acids have been studied in the samples of instant coffee commercialized in Spain. The studies about contents of food components should be complemented with either in vitro or in vivo bioaccessibility studies to know the amount of food components effectively available for functions in the human body. In this sense, a widely used in vitro model has been applied to assess the potential intestinal absorption of phenolic compounds and organic acids. The contents of hydroxycinnamic acids and flavonols were higher in instant regular coffee samples than in the decaffeinated ones. Bioaccessible phenolic compounds in most analyzed samples account for 20-25% of hydroxycinnamic acids and 17-26% of flavonols. This could mean that a great part of them can remain in the gut, acting as potential in situ antioxidants. Quinic, acetic, pyroglutamic, citric and fumaric acids were identified in commercial instant coffee samples. Succinic acid was found in the coffee blend containing chicory. All carboxylic acids showed a very high bioaccessibility. Particularly, acetic acid and quinic acid were found in higher contents in the samples treated with the in vitro simulation of gastrointestinal processes, compared to the original ones, which can be explained by their cleavage from chlorogenic acid during digestion. This is considered as a positive effect, since quinic acid is considered as an antioxidant inducer. PMID- 27191054 TI - Patient Education Materials in Dermatology: Addressing the Health Literacy Needs of Patients. PMID- 27191053 TI - GGIP: Structure and sequence-based GPCR-GPCR interaction pair predictor. AB - G Protein-Coupled Receptors (GPCRs) are important pharmaceutical targets. More than 30% of currently marketed pharmaceutical medicines target GPCRs. Numerous studies have reported that GPCRs function not only as monomers but also as homo- or hetero-dimers or higher-order molecular complexes. Many GPCRs exert a wide variety of molecular functions by forming specific combinations of GPCR subtypes. In addition, some GPCRs are reportedly associated with diseases. GPCR oligomerization is now recognized as an important event in various biological phenomena, and many researchers are investigating this subject. We have developed a support vector machine (SVM)-based method to predict interacting pairs for GPCR oligomerization, by integrating the structure and sequence information of GPCRs. The performance of our method was evaluated by the Receiver Operating Characteristic (ROC) curve. The corresponding area under the curve was 0.938. As far as we know, this is the only prediction method for interacting pairs among GPCRs. Our method could accelerate the analyses of these interactions, and contribute to the elucidation of the global structures of the GPCR networks in membranes. Proteins 2016; 84:1224-1233. (c) 2016 Wiley Periodicals, Inc. PMID- 27191055 TI - Can Attention-Deficit/Hyperactivity Disorder Onset Occur in Adulthood? PMID- 27191056 TI - Trauma management: Chernobyl in Belarus and Ukraine. AB - Although the Chernobyl nuclear disaster happened in the Soviet Union in 1986, we still do not know how the most affected states - Ukraine and Belarus - have managed this tragedy since independence. Drawing on the concept of cultural trauma, this article compares Chernobyl narratives in Belarus and Ukraine over the past 28 years. It shows that national narratives of Chernobyl differ, representing the varying ways in which the state overcomes trauma. Our understanding of post-communist transformations can be improved by analysing trauma management narratives and their importance for new national identity construction. These narratives also bring new insights to our vision of cultural trauma by linking it to ontological insecurity. The article demonstrates how the state can become an arena of trauma process as it commands material and symbolic resources to deal with trauma. In general, it contributes to a better understanding of how the same traumatic event can become a source of solidarity in one community, but a source of hostility in another. PMID- 27191058 TI - Communicating Chaplains' Care: Narrative Documentation in a Neuroscience-Spine Intensive Care Unit. AB - Chaplaincy care is different for every patient; a growing challenge is to ensure that electronic health records function to support personalized care. While ICU health care teams have advanced clinical practice guidelines to identify and integrate relevant aspects of the patient's story into whole person care, recommendations for documentation are rare. This qualitative study of over 400 free-text EHR notes offers unique insight into current use of free-text documentation in ICU by six chaplains integrated into the healthcare team. Our research provides insight into the phenomena chaplains record in the electronic record. Content analysis shows recurrent report of patient and family practices, beliefs, coping mechanisms, concerns, emotional resources and needs, family and faith support, medical decision making and medical communications. These findings are important for health care team discussions of factors deemed essential to whole person care in ICUs, and, by extension have the potential to support the development of EHR designs that aim to advance personalized care. PMID- 27191057 TI - Campylobacter jejuni adenosine triphosphate phosphoribosyltransferase is an active hexamer that is allosterically controlled by the twisting of a regulatory tail. AB - Adenosine triphosphate phosphoribosyltransferase (ATP-PRT) catalyzes the first committed step of the histidine biosynthesis in plants and microorganisms. Here, we present the functional and structural characterization of the ATP-PRT from the pathogenic epsilon-proteobacteria Campylobacter jejuni (CjeATP-PRT). This enzyme is a member of the long form (HisGL ) ATP-PRT and is allosterically inhibited by histidine, which binds to a remote regulatory domain, and competitively inhibited by AMP. In the crystalline form, CjeATP-PRT was found to adopt two distinctly different hexameric conformations, with an open homohexameric structure observed in the presence of substrate ATP, and a more compact closed form present when inhibitor histidine is bound. CjeATP-PRT was observed to adopt only a hexameric quaternary structure in solution, contradicting previous hypotheses favoring an allosteric mechanism driven by an oligomer equilibrium. Instead, this study supports the conclusion that the ATP-PRT long form hexamer is the active species; the tightening of this structure in response to remote histidine binding results in an inhibited enzyme. PMID- 27191059 TI - Self-assembled triangular DNA nanoparticles are an efficient system for gene delivery. AB - Developing an advanced nucleic acid drug delivery system is of great significance in order to achieve optimal gene delivery. Self-assembled nucleic acid nanoparticles are an excellent platform for the delivery of nucleic acids and other small molecular drugs. In this study, we developed the efficient, three stranded, RNA/DNA hybrid triangular self-assembled nanoparticles, namely, mTOR single-stranded siRNA-loaded triangular DNA nanoparticles (ssRNA-TNP). The ssRNA TNP is formed by the complementary association of the above mentioned three components and is more stable in complete medium than standard duplex siRNA. It could be efficiently transfected into NCI-H292 cells in a dose- and time dependent manner, resulting in high transfection efficiency. Furthermore, ssRNA TNP uptake is dependent on macropinocytosis and clathrin-mediated endocytosis pathways. Interestingly, ssRNA-TNP is more efficient to inhibit the expression of mTOR. This ssRNA-TNP has a simpler structure, better stability, and higher transfection efficiency; therefore it may become a novel nonviral nanosystem for gene delivery. PMID- 27191061 TI - Re: Prospective Evaluation of(99m)Tc-Sestamibi SPECT/CT for the Diagnosis of Renal Oncocytomas and Hybrid Oncocytic/Chromophobe Tumors. PMID- 27191060 TI - LPS Induces Hyper-Permeability of Intestinal Epithelial Cells. AB - Necrotizing Enterocolitis (NEC) is a severe inflammatory disorder leading to high morbidity and mortality rates. A growing body of evidence demonstrate the key role of the Toll like receptor 4 (TLR4) in NEC. This membranal receptor recognizes lipopolysaccharides (LPS) from the bacterial wall and triggers an inflammatory response. The aim of the present study was to elucidate the effect of LPS on paracellular permeability known to be severely affected in NEC. IEC-18 cells were treated with LPS and the effects on morphology, paracellular permeability and their associated gene and protein expressions were measured. Our results show that LPS down regulated the expression of occludin and ZO-1 mRNAs while up regulating Cdkn1a. In addition LPS caused a significant increase in paracellular permeability and epithelial barrier damage. Finally ZO-1 protein was found to be spatially disarrayed in the intercellular junctions in response to LPS. We conclude that LPS adversely affected the functionality of the intestinal epithelial barrier suggesting a new mechanism by which bacterial infection may contribute to the development of NEC. J. Cell. Physiol. 232: 381-390, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27191062 TI - Re: Genomic Characterization of Upper Tract Urothelial Carcinoma. PMID- 27191063 TI - Re: Oncologic Surveillance after Surgical Resection for Renal Cell Carcinoma: A Novel Risk-Based Approach. PMID- 27191064 TI - Re: Cost-Effectiveness of Neoadjuvant Chemotherapy before Radical Cystectomy for Muscle-Invasive Bladder Cancer. PMID- 27191065 TI - Re: Trends in the Use of Perioperative Chemotherapy for Localized and Locally Advanced Muscle-Invasive Bladder Cancer: A Sign of Changing Tides. PMID- 27191066 TI - Re: Variation in Performance of Candidate Surgical Quality Measures for Muscle Invasive Bladder Cancer by Hospital Type. PMID- 27191067 TI - Re: Validation of an RNA Cell Cycle Progression Score for Predicting Death from Prostate Cancer in a Conservatively Managed Needle Biopsy Cohort. PMID- 27191068 TI - Re: Nadir Testosterone within First Year of Androgen-Deprivation Therapy (ADT) Predicts for Time to Castration-Resistant Progression: A Secondary Analysis of the PR-7 Trial of Intermittent versus Continuous ADT. PMID- 27191069 TI - Re: Statin Use at the Time of Initiation of Androgen Deprivation Therapy and Time to Progression in Patients with Hormone-Sensitive Prostate Cancer. PMID- 27191070 TI - Re: Nine-Year Follow-up for a Study of Diffusion-Weighted Magnetic Resonance Imaging in a Prospective Prostate Cancer Active Surveillance Cohort. PMID- 27191071 TI - Re: Benign Conditions that Mimic Prostate Carcinoma: MR Imaging Features with Histopathologic Correlation. PMID- 27191072 TI - Re: Complications, Recovery, and Early Functional Outcomes and Oncologic Control following In-Bore Focal Laser Ablation of Prostate Cancer. PMID- 27191073 TI - Re: Radiation Exposure from Diagnostic Imaging in Young Patients with Testicular Cancer. PMID- 27191074 TI - Re: For Single Dosing, Levofloxacin is Superior to Ciprofloxacin when Combined with an Aminoglycoside in Preventing Severe Infections after Prostate Biopsy. PMID- 27191076 TI - Re: Wind, Water, Wound, Walk-Do the Data Deliver the Dictum? PMID- 27191075 TI - Re: Potential Burden of Antibiotic Resistance on Surgery and Cancer Chemotherapy Antibiotic Prophylaxis in the USA: A Literature Review and Modelling Study. PMID- 27191077 TI - Re: The Role of Calbindin-D28k on Renal Calcium and Magnesium Handling during Treatment with Loop and Thiazide Diuretics. PMID- 27191078 TI - Re: Penile Lengthening and Widening without Grafting According to a Modified 'Sliding' Technique. PMID- 27191079 TI - Re: Risk of Damage to the Somatic Innervation of the Penis during the AdVance Procedure: An Anatomical Study. PMID- 27191080 TI - Re: Intraoperative Decision-Making for Precise Penile Straightening during Inflatable Penile Prosthesis Surgery. PMID- 27191081 TI - Re: Dorsal versus Ventral Onlay Buccal Mucosal Graft Urethroplasty for Long Segment Bulbar Urethral Stricture: A Prospective Randomized Study. PMID- 27191082 TI - Re: Kidney-Failure Risk Projection for the Living Kidney-Donor Candidate. PMID- 27191083 TI - Re: Urological Surveillance and Medical Complications after Spinal Cord Injury in the United States. PMID- 27191084 TI - Re: Drug Adherence and Clinical Outcomes for Patients under Pharmacological Therapy for Lower Urinary Tract Symptoms Related to Benign Prostatic Hyperplasia: Population-Based Cohort Study. PMID- 27191085 TI - Re: The Underactive Bladder: A New Clinical Concept? PMID- 27191087 TI - Re: Diet Modification for Overactive Bladder: An Evidence-Based Review. PMID- 27191086 TI - Re: Health-Related Quality of Life and Outcomes after Surgical Treatment of Complications from Vaginally Placed Mesh. PMID- 27191088 TI - Re: "Stain in Life": The Meaning of Urinary Incontinence in the Context of Muslim Postmenopausal Women through Hermeneutic Phenomenology. PMID- 27191089 TI - Re: Efficacy of Electromagnetic Therapy for Urinary Incontinence: A Systematic Review. PMID- 27191090 TI - Re: A Randomized, Controlled Trial of Effectiveness and Safety of Management of OAB Symptoms in Elderly Men and Women with Standard-Dosed Combination of Solifenacin and Mirabegron. PMID- 27191091 TI - Re: The Effect of Conservative Treatment of Urinary Incontinence among Older and Frail Older People: A Systematic Review. PMID- 27191092 TI - Re: 5-Alpha-Reductase Inhibitors and the Risk of Diabetes Mellitus: A Nationwide Population-Based Study. PMID- 27191093 TI - Re: Can Bladder Wall Thickness Measurement be Used for Detecting Bladder Outlet Obstruction? PMID- 27191094 TI - Re: Bladder Function in Obstructed Men-Does Age Matter? PMID- 27191095 TI - Re: Temporary Implantable Nitinol Device (TIND): A Novel, Minimally Invasive Treatment for Relief of Lower Urinary Tract Symptoms (LUTS) Related to Benign Prostatic Hyperplasia (BPH): Feasibility, Safety and Functional Results at 1 Year of Follow-up. PMID- 27191096 TI - Re: Central Obesity is Predictive of Persistent Storage Lower Urinary Tract Symptoms (LUTS) after Surgery for Benign Prostatic Enlargement: Results of a Multicentre Prospective Study. PMID- 27191097 TI - Re: Resveratrol Reduces the Levels of Circulating Androgen Precursors but has No Effect on Testosterone, Dihydrotestosterone, PSA Levels or Prostate Volume. A 4 Month Randomised Trial in Middle-Aged Men. PMID- 27191098 TI - Re: Systematic Review and Meta-Analysis of Candidate Gene Association Studies of Lower Urinary Tract Symptoms in Men. PMID- 27191099 TI - Re: Hypogonadism and Mortality in Aged Hospitalized Male Patients: A 5-Year Prospective Observational Study. PMID- 27191100 TI - Re: Effect of Levitra on Sustenance of Erection (EROS): An Open-Label, Prospective, Multicenter, Single-Arm Study to Investigate Erection Duration Measured by Stopwatch with Flexible Dose Vardenafil Administered for 8 Weeks in Subjects with Erectile Dysfunction. PMID- 27191101 TI - Re: The Effect of Testosterone on Cardiometabolic Risk Factors in Atorvastatin Treated Men with Late-Onset Hypogonadism. PMID- 27191102 TI - Re: Introduction: Ejaculatory Problems and Male Infertility. PMID- 27191103 TI - Re: Therapy of Endocrine Disease: Testosterone Supplementation and Body Composition: Results from a Meta-Analysis Study. PMID- 27191104 TI - Re: Urinary Concentrations of Benzophenone-Type Ultraviolet Light Filters and Semen Quality. PMID- 27191105 TI - Re: Outcomes of Microscopic Subinguinal Varicocelectomy with and without the Assistance of Doppler Ultrasound: A Randomized Clinical Trial. PMID- 27191106 TI - Re: Varicocele Negatively Affects Sperm Mitochondrial Respiration. PMID- 27191107 TI - Re: Men's Meat Intake and Treatment Outcomes among Couples Undergoing Assisted Reproduction. PMID- 27191108 TI - Re: Access to Care and Affordability have Improved following Affordable Care Act Implementation; Problems Remain. PMID- 27191109 TI - Re: Profiling Individual Surgeon Performance Using Information from a High Quality Clinical Registry: Opportunities and Limitations. PMID- 27191110 TI - Re: Successful Pregnancy in Patients with Exstrophy-Epispadias Complex: A University of Washington Experience. PMID- 27191111 TI - Re: 30-Day Morbidity after Augmentation Enterocystoplasty and Appendicovesicostomy: A NSQIP Pediatric Analysis. PMID- 27191112 TI - Re: Is it Safe to Solely Use Ventral Penile Tissues in Hypospadias Repair? Long Term Outcomes of 578 Duplay Urethroplasties Performed in a Single Institution over a Period of 14 Years. PMID- 27191113 TI - Re: Self-Cathing Experience Journal: Enhancing the Patient and Family Experience in Clean Intermittent Catheterization. PMID- 27191114 TI - Re: Robot-Assisted Laparoscopic Augmentation Ileocystoplasty and Mitrofanoff Appendicovesicostomy in Children: Updated Interim Results. PMID- 27191115 TI - Re: Infiltrating Neutrophils Promote Renal Cell Carcinoma (RCC) Proliferation via Modulating Androgen Receptor (AR) -> c-Myc Signals. PMID- 27191116 TI - Re: Marked Protection against Acute Renal and Hepatic Injury after Nitrited Myoglobin + Tin Protoporphyrin Administration. PMID- 27191117 TI - Re: Autophagy Defects Suggested by Low Levels of Autophagy Activator MAP1S and High Levels of Autophagy Inhibitor LRPPRC Predict Poor Prognosis of Prostate Cancer Patients. PMID- 27191119 TI - Re: Characterization of Urinary Stone Composition by Use of Third-Generation Dual Source Dual-Energy CT with Increased Spectral Separation. PMID- 27191118 TI - Re: Detection of Different Kidney Stone Types: An Ex Vivo Comparison of Ultrashort Echo Time MRI to Reference Standard CT. PMID- 27191121 TI - Ultrabrief Electroconvulsive Therapy for Mania: Data From 11 Acute Treatment Courses. AB - Electroconvulsive therapy (ECT) is an effective treatment of mania. Ultrabrief ECT is a novel modality that is associated with fewer cognitive adverse effects than the standard pulse width brief pulse ECT. It has been well studied in depression. However, its use in mania is not yet known. Following a retrospective chart view, we report a small sample of patients who had Right Unilateral Ultrabrief ECT (RUB-ECT) for mania. Eleven RUB-ECTs were identified for 9 patients; 72.8% remission rate was observed with RUB-ECT. Two patients required switch into bitemporal ECT in view of minimal clinical response and 1 patient to right unilateral brief pulse ECT because of poor seizure parameters. All patients achieved remission eventually. The possible mechanisms of ECT in mania and clinical implications of ultrabrief ECT are discussed. PMID- 27191122 TI - Differences in Cognitive Outcomes After ECT Depending on BDNF and COMT Polymorphisms. AB - OBJECTIVE: The study aimed to explore cognitive outcomes after electroconvulsive therapy (ECT) depending on which version of common single nucleotide polymorphisms the patient expressed for brain-derived neurotrophic factor (BDNF) and catechol-O-methyltransferase (COMT). METHODS: A total of 87 patients from the clinical ECT service in Aberdeen, Scotland, were included in the study. Cognitive function testing (using Spatial Recognition Memory task from the Cambridge Neuropsychological Test Automated Battery and Mini-Mental State Examination) and mood ratings (Montgomery-Asberg Depression Rating Scale) were performed before ECT, after 4 treatments, at the end of ECT and 1 and 3 months after the end of treatment. These scores were compared depending on BDNF and COMT variant at each time point using the Student t test and using a time series generalized least squares random effects model. RESULTS: No differences were found between the val and met versions of the BDNF or COMT polymorphism in either cognitive or mood outcomes at any time point during ECT treatment or up to 3 months of follow-up. CONCLUSIONS: This study did not detect significant differences in cognitive or mood outcomes between patients who have the val66val or met versions of the BDNF polymorphism. Our results suggest that these polymorphisms will not be helpful in clinical practice for predicting cognitive outcomes after ECT. PMID- 27191123 TI - The FDA and ECT. PMID- 27191151 TI - Cancer comes of age embryonically. PMID- 27191125 TI - Folic acid fortification and prevalences of neural tube defects, orofacial clefts, and gastroschisis in California, 1989 to 2010. AB - BACKGROUND: We examined whether prevalences of neural tube defects (NTDs), orofacial clefts, and gastroschisis changed more rapidly after than before folic acid fortification in California. METHODS: This population-based study used vital statistics and birth defects registry data. The study population included all live births and stillbirths delivered in central California counties from 1989 to 2010. Cases included deliveries with NTDs, orofacial clefts, and gastroschisis. Weighted least squares regression was used to estimate slopes during prefortification (before 1997) and postfortification (after 1998), respectively. The difference of the two slopes with the 95% confidence interval (CI) was calculated. RESULTS: For all NTDs combined, slopes indicated that NTD prevalence was decreasing by 8.7 (slope: -8.7; 95% CI, -13.5--3.9) cases per 100,000 deliveries per year before fortification and by 1.7 (slope: -1.7; 95% CI, -3.7 0.3) after fortification; thus the decline had slowed by 7.0 (95% CI, 2.7-11.3) cases per 100,000 deliveries per year. For orofacial clefts, slopes for cleft lip with/without palate as well as for cleft palate alone indicated that the postfortification slope was lower than the prefortification slope suggesting a more accelerated decrease in the postfortification time period. For gastroschisis, the slope after fortification was lower compared with prefortification, indicating a less accelerated prevalence increase in the postfortification time period. Stratification by race/ethnicity did not substantially alter results. CONCLUSION: We observed a slower decline in prevalence of NTDs, an emergence of a decline in orofacial clefts, and a slower increase in gastroschisis, during the postfortification period in central California, relative to the prefortification period. Birth Defects Research (Part A), 2016. (c) 2016 Wiley Periodicals, Inc. Birth Defects Research (Part A) 106:1032-1041, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27191152 TI - AQP2-Induced Acceleration of Renal Cell Proliferation Involves the Activation of a Regulatory Volume Increase Mechanism Dependent on NHE2. AB - We have previously shown in renal cells that expression of the water channel Aquaporin 2 (AQP2) increases the rate of cell proliferation by shortening the transit time through the S and G2 /M phases of the cell cycle. This acceleration is due, at least in part, to a down-regulation of regulatory volume decrease (RVD) mechanisms when volume needs to be increased in order to proceed into the S phase. We hypothesize that in order to increase cell volume, RVD mechanisms may be overtaken by regulatory volume increase mechanisms (RVI). In this study, we investigated if the isoform 2 of the Na+ /H+ exchanger (NHE2), the main ion transporter involved in RVI responses, contributed to the AQP2-increased renal cell proliferation. Three cortical collecting duct cell lines were used: WT-RCCD1 (not expressing AQPs), AQP2-RCCD1 (transfected with AQP2), and mpkCCDc14 (with inducible AQP2 expression). We here demonstrate, for the first time, that both NHE2 protein activity and expression were increased in AQP2-expressing cells. NHE2 inhibition decreased cell proliferation and delayed cell cycle progression by slowing S and G2 /M phases only if AQP2 was expressed. Finally, we observed that only in AQP2-expressing cells a NHE2-dependent RVI response was activated in the S phase. These observations suggest that the AQP2-increased proliferation involves the activation of a regulatory volume increase mechanism dependent on NHE2. Therefore, we propose that the accelerated proliferation of AQP2-expressing cells requires a coordinated modulation of the RVD/RVI activity that contributes to cell volume changes during cell cycle progression. J. Cell. Biochem. 118: 967 978, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27191126 TI - Acetyl L-carnitine targets adenosine triphosphate synthase in protecting zebrafish embryos from toxicities induced by verapamil and ketamine: An in vivo assessment. AB - Verapamil is a Ca2+ channel blocker and is highly prescribed as an anti-anginal, antiarrhythmic and antihypertensive drug. Ketamine, an antagonist of the Ca2+ permeable N-methyl-d-aspartate-type glutamate receptors, is a pediatric anesthetic. Previously we have shown that acetyl l-carnitine (ALCAR) reverses ketamine-induced attenuation of heart rate and neurotoxicity in zebrafish embryos. Here, we used 48 h post-fertilization zebrafish embryos that were exposed to relevant drugs for 2 or 4 h. Heart beat and overall development were monitored in vivo. In 48 h post-fertilization embryos, 2 mm ketamine reduced heart rate in a 2 or 4 h exposure and 0.5 mm ALCAR neutralized this effect. ALCAR could reverse ketamine's effect, possibly through a compensatory mechanism involving extracellular Ca2+ entry through L-type Ca2+ channels that ALCAR is known to activate. Hence, we used verapamil to block the L-type Ca2+ channels. Verapamil was more potent in attenuating heart rate and inducing morphological defects in the embryos compared to ketamine at specific times of exposure. ALCAR reversed cardiotoxicity and developmental toxicity in the embryos exposed to verapamil or verapamil plus ketamine, even in the presence of 3,4,5 trimethoxybenzoic acid 8-(diethylamino)octyl ester, an inhibitor of intracellular Ca2+ release suggesting that ALCAR acts via effectors downstream of Ca2+ . In fact, ALCAR's protective effect was blunted by oligomycin A, an inhibitor of adenosine triphosphate synthase that acts downstream of Ca2+ during adenosine triphosphate generation. We have identified, for the first time, using in vivo studies, a downstream effector of ALCAR that is critical in abrogating ketamine- and verapamil-induced developmental toxicities. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. PMID- 27191153 TI - Digital disease detection and participatory surveillance: overview and perspectives for Brazil. AB - This study aimed to describe the digital disease detection and participatory surveillance in different countries. The systems or platforms consolidated in the scientific field were analyzed by describing the strategy, type of data source, main objectives, and manner of interaction with users. Eleven systems or platforms, developed from 1996 to 2016, were analyzed. There was a higher frequency of data mining on the web and active crowdsourcing as well as a trend in the use of mobile applications. It is important to provoke debate in the academia and health services for the evolution of methods and insights into participatory surveillance in the digital age. PMID- 27191154 TI - Relationship of health workers with their organization and work: a cross-cultural study. AB - We analyzed the differences, by Student's t-test and ANOVA, between nurses and physicians from Portugal, Poland, Spain, and United Kingdom regarding their relationship with their work and organization. In total, 1,401 professionals answered the HSA-QHPR questionnaire. There are different levels of connection between physicians and nurses. The United Kingdom has the lowest levels of connection with the work while Portugal has the highest levels of relationship with the organization. The results provide guidelines for the development of policies and differential strategies aimed at improving the quality of healthcare service. PMID- 27191155 TI - Difficulties in access and estimates of public beds in intensive care units in the state of Rio de Janeiro. AB - OBJECTIVE: To estimate the required number of public beds for adults in intensive care units in the state of Rio de Janeiro to meet the existing demand and compare results with recommendations by the Brazilian Ministry of Health. METHODS: The study uses a hybrid model combining time series and queuing theory to predict the demand and estimate the number of required beds. Four patient flow scenarios were considered according to bed requests, percentage of abandonments and average length of stay in intensive care unit beds. The results were plotted against Ministry of Health parameters. Data were obtained from the State Regulation Center from 2010 to 2011. RESULTS: There were 33,101 medical requests for 268 regulated intensive care unit beds in Rio de Janeiro. With an average length of stay in regulated ICUs of 11.3 days, there would be a need for 595 active beds to ensure system stability and 628 beds to ensure a maximum waiting time of six hours. Deducting current abandonment rates due to clinical improvement (25.8%), these figures fall to 441 and 417. With an average length of stay of 6.5 days, the number of required beds would be 342 and 366, respectively; deducting abandonment rates, 254 and 275. The Brazilian Ministry of Health establishes a parameter of 118 to 353 beds. Although the number of regulated beds is within the recommended range, an increase in beds of 122.0% is required to guarantee system stability and of 134.0% for a maximum waiting time of six hours. CONCLUSIONS: Adequate bed estimation must consider reasons for limited timely access and patient flow management in a scenario that associates prioritization of requests with the lowest average length of stay. PMID- 27191156 TI - Spatial analysis of avoidable hospitalizations due to tuberculosis in Ribeirao Preto, SP, Brazil (2006-2012). AB - OBJECTIVE: To describe the spatial distribution of avoidable hospitalizations due to tuberculosis in the municipality of Ribeirao Preto, SP, Brazil, and to identify spatial and space-time clusters for the risk of occurrence of these events. METHODS: This is a descriptive, ecological study that considered the hospitalizations records of the Hospital Information System of residents of Ribeirao Preto, SP, Southeastern Brazil, from 2006 to 2012. Only the cases with recorded addresses were considered for the spatial analyses, and they were also geocoded. We resorted to Kernel density estimation to identify the densest areas, local empirical Bayes rate as the method for smoothing the incidence rates of hospital admissions, and scan statistic for identifying clusters of risk. Softwares ArcGis 10.2, TerraView 4.2.2, and SaTScanTM were used in the analysis. RESULTS: We identified 169 hospitalizations due to tuberculosis. Most were of men (n = 134; 79.2%), averagely aged 48 years (SD = 16.2). The predominant clinical form was the pulmonary one, which was confirmed through a microscopic examination of expectorated sputum (n = 66; 39.0%). We geocoded 159 cases (94.0%). We observed a non-random spatial distribution of avoidable hospitalizations due to tuberculosis concentrated in the northern and western regions of the municipality. Through the scan statistic, three spatial clusters for risk of hospitalizations due to tuberculosis were identified, one of them in the northern region of the municipality (relative risk [RR] = 3.4; 95%CI 2.7-4,4); the second in the central region, where there is a prison unit (RR = 28.6; 95%CI 22.4-36.6); and the last one in the southern region, and area of protection for hospitalizations (RR = 0.2; 95%CI 0.2-0.3). We did not identify any space-time clusters. CONCLUSIONS: The investigation showed priority areas for the control and surveillance of tuberculosis, as well as the profile of the affected population, which shows important aspects to be considered in terms of management and organization of health care services targeting effectiveness in primary health care. PMID- 27191157 TI - Work, malaise, and well-being in Spanish and Latin-American doctors. AB - OBJECTIVE: To analyze the relations between the meanings of working and the levels of doctors work well-being in the context of their working conditions. METHOD: The research combined the qualitative methodology of textual analysis and the quantitative one of correspondence factor analysis. A convenience, intentional, and stratified sample composed of 305 Spanish and Latin American doctors completed an extensive questionnaire on the topics of the research. RESULTS: The general meaning of working for the group located in the quartile of malaise included perceptions of discomfort, frustration, and exhaustion. However, those showing higher levels of well-being, located on the opposite quartile, associated their working experience with good conditions and the development of their professional and personal competences. CONCLUSIONS: The study provides empirical evidence of the relationship between contextual factors and the meanings of working for participants with higher levels of malaise, and of the importance granted both to intrinsic and extrinsic factors by those who scored highest on well-being. PMID- 27191158 TI - Dynamic network data envelopment analysis for university hospitals evaluation. AB - OBJECTIVE: To develop an assessment tool to evaluate the efficiency of federal university general hospitals. METHODS: Data envelopment analysis, a linear programming technique, creates a best practice frontier by comparing observed production given the amount of resources used. The model is output-oriented and considers variable returns to scale. Network data envelopment analysis considers link variables belonging to more than one dimension (in the model, medical residents, adjusted admissions, and research projects). Dynamic network data envelopment analysis uses carry-over variables (in the model, financing budget) to analyze frontier shift in subsequent years. Data were gathered from the information system of the Brazilian Ministry of Education (MEC), 2010-2013. RESULTS: The mean scores for health care, teaching and research over the period were 58.0%, 86.0%, and 61.0%, respectively. In 2012, the best performance year, for all units to reach the frontier it would be necessary to have a mean increase of 65.0% in outpatient visits; 34.0% in admissions; 12.0% in undergraduate students; 13.0% in multi-professional residents; 48.0% in graduate students; 7.0% in research projects; besides a decrease of 9.0% in medical residents. In the same year, an increase of 0.9% in financing budget would be necessary to improve the care output frontier. In the dynamic evaluation, there was progress in teaching efficiency, oscillation in medical care and no variation in research. CONCLUSIONS: The proposed model generates public health planning and programming parameters by estimating efficiency scores and making projections to reach the best practice frontier. PMID- 27191160 TI - Biochar Improves Soil Aggregate Stability and Water Availability in a Mollisol after Three Years of Field Application. AB - A field experiment was carried out to evaluate the effect of organic amendments on soil organic carbon, total nitrogen, bulk density, aggregate stability, field capacity and plant available water in a representative Chinese Mollisol. Four treatments were as follows: no fertilization (CK), application of inorganic fertilizer (NPK), combined application of inorganic fertilizer with maize straw (NPK+S) and addition of biochar with inorganic fertilizer (NPK+B). Our results showed that after three consecutive years of application, the values of soil bulk density were significantly lower in both organic amendment-treated plots than in unamended (CK and NPK) plots. Compared with NPK, NPK+B more effectively increased the contents of soil organic carbon, improved the relative proportion of soil macro-aggregates and mean weight diameter, and enhanced field capacity as well as plant available water. Organic amendments had no obvious effect on soil C/N ratio or wilting coefficient. The results of linear regression indicated that the improvement in soil water retention could be attributed to the increases in soil organic carbon and aggregate stability. PMID- 27191162 TI - Facial Recognition in a Discus Fish (Cichlidae): Experimental Approach Using Digital Models. AB - A number of mammals and birds are known to be capable of visually discriminating between familiar and unfamiliar individuals, depending on facial patterns in some species. Many fish also visually recognize other conspecifics individually, and previous studies report that facial color patterns can be an initial signal for individual recognition. For example, a cichlid fish and a damselfish will use individual-specific color patterns that develop only in the facial area. However, it remains to be determined whether the facial area is an especially favorable site for visual signals in fish, and if so why? The monogamous discus fish, Symphysopdon aequifasciatus (Cichlidae), is capable of visually distinguishing its pair-partner from other conspecifics. Discus fish have individual-specific coloration patterns on entire body including the facial area, frontal head, trunk and vertical fins. If the facial area is an inherently important site for the visual cues, this species will use facial patterns for individual recognition, but otherwise they will use patterns on other body parts as well. We used modified digital models to examine whether discus fish use only facial coloration for individual recognition. Digital models of four different combinations of familiar and unfamiliar fish faces and bodies were displayed in frontal and lateral views. Focal fish frequently performed partner-specific displays towards partner-face models, and did aggressive displays towards models of non-partner's faces. We conclude that to identify individuals this fish does not depend on frontal color patterns but does on lateral facial color patterns, although they have unique color patterns on the other parts of body. We discuss the significance of facial coloration for individual recognition in fish compared with birds and mammals. PMID- 27191161 TI - Characterization of Yellow Fever Virus Infection of Human and Non-human Primate Antigen Presenting Cells and Their Interaction with CD4+ T Cells. AB - Humans infected with yellow fever virus (YFV), a mosquito-borne flavivirus, can develop illness ranging from a mild febrile disease to hemorrhagic fever and death. The 17D vaccine strain of YFV was developed in the 1930s, has been used continuously since development and has proven very effective. Genetic differences between vaccine and wild-type viruses are few, yet viral or host mechanisms associated with protection or disease are not fully understood. Over the past 20 years, a number of cases of vaccine-associated disease have been identified following vaccination with 17D; these cases have been correlated with reduced immune status at the time of vaccination. Recently, several studies have evaluated T cell responses to vaccination in both humans and non-human primates, but none have evaluated the response to wild-type virus infection. In the studies described here, monocyte-derived macrophages (MDM) and dendritic cells (MoDC) from both humans and rhesus macaques were evaluated for their ability to support infection with either wild-type Asibi virus or the 17D vaccine strain and the host cytokine and chemokine response characterized. Human MoDC and MDM were also evaluated for their ability to stimulate CD4+ T cells. It was found that MoDC and MDM supported viral replication and that there were differential cytokine responses to infection with either wild-type or vaccine viruses. Additionally, MoDCs infected with live 17D virus were able to stimulate IFN-gamma and IL-2 production in CD4+ T cells, while cells infected with Asibi virus were not. These data demonstrate that wild-type and vaccine YFV stimulate different responses in target antigen presenting cells and that wild-type YFV can inhibit MoDC activation of CD4+ T cells, a critical component in development of protective immunity. These data provide initial, but critical insight into regulatory capabilities of wild-type YFV in development of disease. PMID- 27191163 TI - Impact on Bacterial Resistance of Therapeutically Nonequivalent Generics: The Case of Piperacillin-Tazobactam. AB - Previous studies have demonstrated that pharmaceutical equivalence and pharmacokinetic equivalence of generic antibiotics are necessary but not sufficient conditions to guarantee therapeutic equivalence (better called pharmacodynamic equivalence). In addition, there is scientific evidence suggesting a direct link between pharmacodynamic nonequivalence of generic vancomycin and promotion of resistance in Staphylococcus aureus. To find out if even subtle deviations from the expected pharmacodynamic behavior with respect to the innovator could favor resistance, we studied a generic product of piperacillin-tazobactam characterized by pharmaceutical and pharmacokinetic equivalence but a faulty fit of Hill's Emax sigmoid model that could be interpreted as pharmacodynamic nonequivalence. We determined the impact in vivo of this generic product on the resistance of a mixed Escherichia coli population composed of ~99% susceptible cells (ATCC 35218 strain) and a ~1% isogenic resistant subpopulation that overproduces TEM-1 beta-lactamase. After only 24 hours of treatment in the neutropenic murine thigh infection model, the generic amplified the resistant subpopulation up to 20-times compared with the innovator, following an inverted-U dose-response relationship. These findings highlight the critical role of therapeutic nonequivalence of generic antibiotics as a key factor contributing to the global problem of bacterial resistance. PMID- 27191164 TI - Morphometric Assessment of Convergent Tool Technology and Function during the Early Middle Palaeolithic: The Case of Payre, France. AB - There appears to be little doubt as to the existence of an intentional technological resolve to produce convergent tools during the Middle Palaeolithic. However, the use of these pieces as pointed tools is still subject to debate: i.e., handheld tool vs. hafted tool. Present-day technological analysis has begun to apply new methodologies in order to quantify shape variability and to decipher the role of the morphology of these pieces in relation to function; for instance, geometric morphometric analyses have recently been applied with successful results. This paper presents a study of this type of analysis on 37 convergent tools from level Ga of Payre site (France), dated to MIS 8-7. These pieces are non-standardized knapping products produced by discoidal and orthogonal core technologies. Moreover, macro-wear studies attest to various activities on diverse materials with no evidence of hafting or projectile use. The aim of this paper is to test the geometric morphometric approach on non-standardized artefacts applying the Elliptical Fourier analysis (EFA) to 3D contours and to assess the potential relationship between size and shape, technology and function. This study is innovative in that it is the first time that this method, considered to be a valuable complement for describing technological and functional attributes, is applied to 3D contours of lithic products. Our results show that this methodology ensures a very good degree of accuracy in describing shape variations of the sharp edges of technologically non-standardized convergent tools. EFA on 3D contours indicates variations in deviations of the outline along the third dimension (i.e., dorso-ventrally) and yields quantitative and insightful information on the actual shape variations of tools. Several statistically significant relationships are found between shape variation and use wear attributes, though the results emphasize the large variability of the shape of the convergent tools, which, in general, does not show a strong direct association with technological features and function. This is in good agreement with the technological context of this chronological period, characterized by a wide diversity of non-standardized tools adapted to multipurpose functions for varied subsistence activities. PMID- 27191166 TI - Cognitive and Ocular Factors Jointly Determine Pupil Responses under Equiluminance. AB - Changes in pupil diameter can reflect high-level cognitive signals that depend on central neuromodulatory mechanisms. However, brain mechanisms that adjust pupil size are also exquisitely sensitive to changes in luminance and other events that would be considered a nuisance in cognitive experiments recording pupil size. We implemented a simple auditory experiment involving no changes in visual stimulation. Using finite impulse-response fitting we found pupil responses triggered by different types of events. Among these are pupil responses to auditory events and associated surprise: cognitive effects. However, these cognitive responses were overshadowed by pupil responses associated with blinks and eye movements, both inevitable nuisance factors that lead to changes in effective luminance. Of note, these latter pupil responses were not recording artifacts caused by blinks and eye movements, but endogenous pupil responses that occurred in the wake of these events. Furthermore, we identified slow (tonic) changes in pupil size that differentially influenced faster (phasic) pupil responses. Fitting all pupil responses using gamma functions, we provide accurate characterisations of cognitive and non-cognitive response shapes, and quantify each response's dependence on tonic pupil size. These results allow us to create a set of recommendations for pupil size analysis in cognitive neuroscience, which we have implemented in freely available software. PMID- 27191167 TI - Effects of Darwinian Selection and Mutability on Rate of Broadly Neutralizing Antibody Evolution during HIV-1 Infection. AB - Accumulation of somatic mutations in antibody variable regions is critical for antibody affinity maturation, with HIV-1 broadly neutralizing antibodies (bnAbs) generally requiring years to develop. We recently found that the rate at which mutations accumulate decreases over time, but the mechanism governing this slowing is unclear. In this study, we investigated whether natural selection and/or mutability of the antibody variable region contributed significantly to observed decrease in rate. We used longitudinally sampled sequences of immunoglobulin transcripts of single lineages from each of 3 donors, as determined by next generation sequencing. We estimated the evolutionary rates of the complementarity determining regions (CDRs), which are most significant for functional selection, and found they evolved about 1.5- to 2- fold faster than the framework regions. We also analyzed the presence of AID hotspots and coldspots at different points in lineage development and observed an average decrease in mutability of less than 10 percent over time. Altogether, the correlation between Darwinian selection strength and evolutionary rate trended toward significance, especially for CDRs, but cannot fully explain the observed changes in evolutionary rate. The mutability modulated by AID hotspots and coldspots changes correlated only weakly with evolutionary rates. The combined effects of Darwinian selection and mutability contribute substantially to, but do not fully explain, evolutionary rate change for HIV-1-targeting bnAb lineages. PMID- 27191169 TI - Different Dimensions of Cognitive Style in Typical and Atypical Cognition: New Evidence and a New Measurement Tool. AB - We developed the Sussex Cognitive Styles Questionnaire (SCSQ) to investigate visual and verbal processing preferences and incorporate global/local processing orientations and systemising into a single, comprehensive measure. In Study 1 (N = 1542), factor analysis revealed six reliable subscales to the final 60 item questionnaire: Imagery Ability (relating to the use of visual mental imagery in everyday life); Technical/Spatial (relating to spatial mental imagery, and numerical and technical cognition); Language & Word Forms; Need for Organisation; Global Bias; and Systemising Tendency. Thus, we replicate previous findings that visual and verbal styles are separable, and that types of imagery can be subdivided. We extend previous research by showing that spatial imagery clusters with other abstract cognitive skills, and demonstrate that global/local bias can be separated from systemising. Study 2 validated the Technical/Spatial and Language & Word Forms factors by showing that they affect performance on memory tasks. In Study 3, we validated Imagery Ability, Technical/Spatial, Language & Word Forms, Global Bias, and Systemising Tendency by issuing the SCSQ to a sample of synaesthetes (N = 121) who report atypical cognitive profiles on these subscales. Thus, the SCSQ consolidates research from traditionally disparate areas of cognitive science into a comprehensive cognitive style measure, which can be used in the general population, and special populations. PMID- 27191170 TI - Data Sources for Trait Databases: Comparing the Phenomic Content of Monographs and Evolutionary Matrices. AB - Databases of organismal traits that aggregate information from one or multiple sources can be leveraged for large-scale analyses in biology. Yet the differences among these data streams and how well they capture trait diversity have never been explored. We present the first analysis of the differences between phenotypes captured in free text of descriptive publications ('monographs') and those used in phylogenetic analyses ('matrices'). We focus our analysis on osteological phenotypes of the limbs of four extinct vertebrate taxa critical to our understanding of the fin-to-limb transition. We find that there is low overlap between the anatomical entities used in these two sources of phenotype data, indicating that phenotypes represented in matrices are not simply a subset of those found in monographic descriptions. Perhaps as expected, compared to characters found in matrices, phenotypes in monographs tend to emphasize descriptive and positional morphology, be somewhat more complex, and relate to fewer additional taxa. While based on a small set of focal taxa, these qualitative and quantitative data suggest that either source of phenotypes alone will result in incomplete knowledge of variation for a given taxon. As a broader community develops to use and expand databases characterizing organismal trait diversity, it is important to recognize the limitations of the data sources and develop strategies to more fully characterize variation both within species and across the tree of life. PMID- 27191168 TI - Direct and Indirect Targeting of PP2A by Conserved Bacterial Type-III Effector Proteins. AB - Bacterial AvrE-family Type-III effector proteins (T3Es) contribute significantly to the virulence of plant-pathogenic species of Pseudomonas, Pantoea, Ralstonia, Erwinia, Dickeya and Pectobacterium, with hosts ranging from monocots to dicots. However, the mode of action of AvrE-family T3Es remains enigmatic, due in large part to their toxicity when expressed in plant or yeast cells. To search for targets of WtsE, an AvrE-family T3E from the maize pathogen Pantoea stewartii subsp. stewartii, we employed a yeast-two-hybrid screen with non-lethal fragments of WtsE and a synthetic genetic array with full-length WtsE. Together these screens indicate that WtsE targets maize protein phosphatase 2A (PP2A) heterotrimeric enzyme complexes via direct interaction with B' regulatory subunits. AvrE1, another AvrE-family T3E from Pseudomonas syringae pv. tomato strain DC3000 (Pto DC3000), associates with specific PP2A B' subunit proteins from its susceptible host Arabidopsis that are homologous to the maize B' subunits shown to interact with WtsE. Additionally, AvrE1 was observed to associate with the WtsE-interacting maize proteins, indicating that PP2A B' subunits are likely conserved targets of AvrE-family T3Es. Notably, the ability of AvrE1 to promote bacterial growth and/or suppress callose deposition was compromised in Arabidopsis plants with mutations of PP2A genes. Also, chemical inhibition of PP2A activity blocked the virulence activity of both WtsE and AvrE1 in planta. The function of HopM1, a Pto DC3000 T3E that is functionally redundant to AvrE1, was also impaired in specific PP2A mutant lines, although no direct interaction with B' subunits was observed. These results indicate that sub component specific PP2A complexes are targeted by bacterial T3Es, including direct targeting by members of the widely conserved AvrE-family. PMID- 27191165 TI - Drug-Based Lead Discovery: The Novel Ablative Antiretroviral Profile of Deferiprone in HIV-1-Infected Cells and in HIV-Infected Treatment-Naive Subjects of a Double-Blind, Placebo-Controlled, Randomized Exploratory Trial. AB - Antiretrovirals suppress HIV-1 production yet spare the sites of HIV-1 production, the HIV-1 DNA-harboring cells that evade immune detection and enable viral resistance on-drug and viral rebound off-drug. Therapeutic ablation of pathogenic cells markedly improves the outcome of many diseases. We extend this strategy to HIV-1 infection. Using drug-based lead discovery, we report the concentration threshold-dependent antiretroviral action of the medicinal chelator deferiprone and validate preclinical findings by a proof-of-concept double-blind trial. In isolate-infected primary cultures, supra-threshold concentrations during deferiprone monotherapy caused decline of HIV-1 RNA and HIV-1 DNA; did not allow viral breakthrough for up to 35 days on-drug, indicating resiliency against viral resistance; and prevented, for at least 87 days off-drug, viral rebound. Displaying a steep dose-effect curve, deferiprone produced infection-independent deficiency of hydroxylated hypusyl-eIF5A. However, unhydroxylated deoxyhypusyl eIF5A accumulated particularly in HIV-infected cells; they preferentially underwent apoptotic DNA fragmentation. Since the threshold, ascertained at about 150 MUM, is achievable in deferiprone-treated patients, we proceeded from cell culture directly to an exploratory trial. HIV-1 RNA was measured after 7 days on drug and after 28 and 56 days off-drug. Subjects who attained supra-threshold concentrations in serum and completed the protocol of 17 oral doses, experienced a zidovudine-like decline of HIV-1 RNA on-drug that was maintained off-drug without statistically significant rebound for 8 weeks, over 670 times the drug's half-life and thus clearance from circulation. The uniform deferiprone threshold is in agreement with mapping of, and crystallographic 3D-data on, the active site of deoxyhypusyl hydroxylase (DOHH), the eIF5A-hydroxylating enzyme. We propose that deficiency of hypusine-containing eIF5A impedes the translation of mRNAs encoding proline cluster ('polyproline')-containing proteins, exemplified by Gag/p24, and facilitated by the excess of deoxyhypusine-containing eIF5A, releases the innate apoptotic defense of HIV-infected cells from viral blockade, thus depleting the cellular reservoir of HIV-1 DNA that drives breakthrough and rebound. TRIAL REGISTRATION: ClinicalTrial.gov NCT02191657. PMID- 27191171 TI - Prospective Validation of Cessation of Contact Precautions for Extended-Spectrum beta-Lactamase-Producing Escherichia coli(1). AB - After contact precautions were discontinued, we determined nosocomial transmission of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli by screening hospital patients who shared rooms with ESBL-producing E. coli infected or -colonized patients. Transmission rates were 2.6% and 8.8% at an acute-care and a geriatric/rehabilitation hospital, respectively. Prolonged contact was associated with increased transmission. PMID- 27191172 TI - Nonoperative Management of Extravasation Injuries Associated With Neonatal Parenteral Nutrition Using Multiple Punctures and a Hydrocolloid Dressing. AB - INTRODUCTION: Neonatal extravasation injuries are often associated with peripheral parenteral nutrition. Several treatment modalities have been developed and used for managing these injuries with variable results. However, there is a lack of consensus regarding the management of neonatal extravasation injuries. The aim of this paper is to introduce a new nonoperative method for the treatment of neonatal extravasation injuries associated with parenteral nutrition. METHODS: The authors made multiple punctures on the extravasated wound using a No. 11 scalpel blade tip and applying a DuoDERM Extra Thin (ConvaTec Inc, Princeton, NJ) dressing, a hydrocolloid dressing. The dressing was changed every 6 hours on the first day, and dressing changes were continued with decreasing frequency according to the amount of exudate until the wound healed. After the devitalized tissue began to demarcate and autolyse, surgical debridement was gradually performed. RESULTS: Twelve neonatal extravasation injuries, which occurred between November 2010 and June 2014, were evaluated. The mean follow-up duration was 10 months. The average duration of treatment for wound healing was 25 days. All wounds healed without func- tional deficits and conspicuous scars. CONCLUSION: The authors suggest their new method of using multiple punctures and a hydrocolloid dressing is an easy, effective, and minimally invasive treatment for neonatal extravasation injuries associated with peripheral parenteral nutrition, and it can be used as an alternative treatment option. PMID- 27191173 TI - The Use of Micronized Dehydrated Human Amnion/Chorion Membrane Allograft for the Treatment of Diabetic Foot Ulcers: A Case Series. AB - Diabetic foot ulcers (DFUs) are a common problem in patients with diabetes and are associated with significant morbidity and mortality. Dehydrated human amnion/chorion membrane (dHACM) allografts have been shown to be effective in the treatment of DFUs. A micronization process produces a dHACM powder that can be sprinkled onto irregular wound surfaces or reconstituted with normal saline for injection into tunneling wounds or wound margins. The author presents a case review of 3 patients with chronic plantar surface DFUs treated with micronized dHACM over a 1-month period. Wound duration was at least 8 months, and 2 out of 3 wounds had failed to heal with cryopreserved human fibroblast-derived dermal substitute before treatment with dHACM. Micronized dHACM (40 mg) in powder form was sprinkled onto the plantar ulcers weekly after sharp debridement, followed by standard topical dressings. Weekly dressing change and wound assessment was conducted to determine the rate of closure. Off-loading shoes were provided. Within 4 weeks of the first dHACM application, all 3 wounds had healed: the first after 2 applications, the second after 3 applications, and the last after 4 applications. No adverse events were observed, and the wounds remained healed after 6 months. In the author's practice, the micronized dHACM allograft was easily applied, clinically effective, and well tolerated as a treatment for plantar ulcers in patients with diabetes. PMID- 27191174 TI - Combination Treatment of Artificial Dermis and Basic Fibroblast Growth Factor for Skin Defects: A Histopathological Examination. AB - This study examined a combination of artificial dermis and basic fibroblast growth factor (bFGF) to treat skin defects in clinical cases, and it histopathologically examined the effects on the conditions of recipient beds. MATERIALS AND METHODS: The subjects were 11 patients with skin defects from burn ulcers or traumatic ulcers. In each subject, debridement was performed and subsequently artificial dermis was applied to the defect. The bFGF was used on 1 side (combination therapy) of the artificial dermis and not used on the other side (artificial dermis monotherapy). A histopathological examination was performed on the granulation tissue collected from the recipient bed. The authors also measured skin hardness 6 months after the skin graft. RESULTS: Histologically, the combination therapy site had more extensive capillary angiogenesis than the monotherapy site. The combination therapy site also had capillary walls consisting of thick, large endothelial cells; fibroblast proliferation and activation; and more severe infiltration of inflammatory cells. Skin hardness after the graft was also much softer in the combination therapy. CONCLUSION: The results suggest the usefulness of this combination therapy in the preparation of skin graft beds to improve skin hardness after skin grafts in clinical cases. PMID- 27191175 TI - The Effect of Ethanol Extract of Rose (Rosa damascena) on Intra-abdominal Adhesions After Laparotomy in Rats. AB - BACKGROUND: Abdominal adhesions are pathological connections in peritoneal surfaces that are created after abdominal surgery. The aim of this study was to evaluate the inhibitory effect of Rosa damascena extract on adhesions, considering the antioxidant properties of rose. METHODS: Thirty healthy rats were divided into 3 groups: rats treated by 1% (A) and 5% (B) of R. damascena extract and the con- trol group (C). After administering anesthesia, the abdominal wall was opened and 3 shallow incisions (2 cm) were made on the right wall, and a 2 * 2 piece of peritoneal surface was removed on the left side of the abdominal wall. Then 3 mL of 1% (A) and 5% (B) R. damascena extract was administered into the abdominal cavity. The control group (C) received 3 mL of distilled water. The abdominal cavity was sutured, and a second laparotomy was carried out 14 days later to the created adhesions according to the Canbaz scale, and a histopathologic examination was also performed. All data was analyzed by SPSS volume 16 (Chicago, IL); P less than 0.05 was considered statistically significant. RESULTS: The amount of adhesion in group A was significantly lower than that of group C, 1.4 +/- 1.265 versus 3 +/- 0.816, (P = 0.007). The histological investigation also showed significant differences in the se- verity of fibrosis (P = 0.029) and inflammation (P = 0.009) between groups A and C; all rats in group B (5%) were found dead. CONCLUSION: This study indicated the use of R. damascena at a 1% level resulted in a remarkable decrease of intra-abdominal adhesions after laparotomy in rats. Further studies are necessary on this extract and its derivatives for treatment of such diseases in the human model. PMID- 27191176 TI - Graft-versus-host Disease-associated Angiomatosis Treated With Topical Timolol Solution. AB - INTRODUCTION: Scleroderma-like graft-versus-host disease (GVHD) is an uncommon subtype of chronic GVHD. Vascular lesions rarely arise within areas of scleroderma-like changes and until recent- ly have not been considered to be related entities. Kaffenberg et al1 have grouped this heterogeneous collection of vascular lesions under the term GVHD-associated angiomatosis. Treatment modalities thus far have been mostly ineffective. Topical timolol solution has been used in the treatment of superficial infantile hemangiomas with good success. Here the authors report the first case of GVHD-associated angiomatosis treated with topical timolol solution. METHODS AND MATERIALS: Timolol 0.5% solution was applied daily to 3 lesions on the lower extremities of their patient for 3 months. RESULTS: All lesions decreased in friability and frequency of spontaneous hemorrhage. Le- sions remained stable in size throughout treatment duration, with no growth observed in any lesion. Granulation tissue surrounding all lesions was markedly reduced after the treatment period. CONCLUSION: Topical timolol remains a promising therapeutic option in the treat- ment of GVHD associated angiomatosis. PMID- 27191178 TI - The study on biomass fraction estimate methodology of municipal solid waste incinerator in Korea. AB - In Korea, the amount of greenhouse gases released due to waste materials was 14,800,000 t CO2eq in 2012, which increased from 5,000,000 t CO2eq in 2010. This included the amount released due to incineration, which has gradually increased since 2010. Incineration was found to be the biggest contributor to greenhouse gases, with 7,400,000 t CO2eq released in 2012. Therefore, with regards to the trading of greenhouse gases emissions initiated in 2015 and the writing of the national inventory report, it is important to increase the reliability of the measurements related to the incineration of waste materials. This research explored methods for estimating the biomass fraction at Korean MSW incinerator facilities and compared the biomass fractions obtained with the different biomass fraction estimation methods. The biomass fraction was estimated by the method using default values of fossil carbon fraction suggested by IPCC, the method using the solid waste composition, and the method using incinerator flue gas. The highest biomass fractions in Korean municipal solid waste incinerator facilities were estimated by the IPCC Default method, followed by the MSW analysis method and the Flue gas analysis method. Therefore, the difference in the biomass fraction estimate was the greatest between the IPCC Default and the Flue gas analysis methods. The difference between the MSW analysis and the flue gas analysis methods was smaller than the difference with IPCC Default method. This suggested that the use of the IPCC default method cannot reflect the characteristics of Korean waste incinerator facilities and Korean MSW. IMPLICATIONS: Incineration is one of most effective methods for disposal of municipal solid waste (MSW). This paper investigates the applicability of using biomass content to estimate the amount of CO2 released, and compares the biomass contents determined by different methods in order to establish a method for estimating biomass in the MSW incinerator facilities of Korea. After analyzing the biomass contents of the collected solid waste samples and the flue gas samples, the results were compared with the Intergovernmental Panel on Climate Change (IPCC) method, and it seems that to calculate the biomass fraction it is better to use the flue gas analysis method than the IPCC method. It is valuable to design and operate a real new incineration power plant, especially for the estimation of greenhouse gas emissions. PMID- 27191177 TI - Thiol-Activated HNO Release from a Ruthenium Antiangiogenesis Complex and HIF 1alpha Inhibition for Cancer Therapy. AB - Metallonitrosyl complexes are promising as nitric oxide (NO) donors for the treatment of cardiovascular, endothelial, and pathogenic diseases, as well as cancer. Recently, the reduced form of NO(-) (protonated as HNO, nitroxyl, azanone, isoelectronic with O2) has also emerged as a candidate for therapeutic applications including treatment of acute heart failure and alcoholism. Here, we show that HNO is a product of the reaction of the Ru(II) complex [Ru(bpy)2(SO3)(NO)](+) (1) with glutathione or N-acetyl-L-cysteine, using met myoglobin and carboxy-PTIO (2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1 oxyl-3-oxide) as trapping agents. Characteristic absorption spectroscopic profiles for HNO reactions with met-myoglobin were obtained, as well as EPR evidence from carboxy-PTIO experiments. Importantly, the product HNO counteracted NO-induced as well as hypoxia-induced stabilization of the tumor-suppressor HIF 1alpha in cancer cells. The functional disruption of neovascularization by HNO produced by this metallonitrosyl complex was demonstrated in an in vitro angiogenesis model. This behavior is consistent with HNO biochemistry and contrasts with NO-mediated stabilization of HIF-1alpha. Together, these results demonstrate for the first time thiol-dependent production of HNO by a ruthenium complex and subsequent destabilization of HIF-1alpha. This work suggests that the complex warrants further investigation as a promising antiangiogenesis agent for the treatment of cancer. PMID- 27191179 TI - On source models for (192)Ir HDR brachytherapy dosimetry using model based algorithms. AB - A source model is a prerequisite of all model based dose calculation algorithms. Besides direct simulation, the use of pre-calculated phase space files (phsp source models) and parameterized phsp source models has been proposed for Monte Carlo (MC) to promote efficiency and ease of implementation in obtaining photon energy, position and direction. In this work, a phsp file for a generic (192)Ir source design (Ballester et al 2015) is obtained from MC simulation. This is used to configure a parameterized phsp source model comprising appropriate probability density functions (PDFs) and a sampling procedure. According to phsp data analysis 15.6% of the generated photons are absorbed within the source, and 90.4% of the emergent photons are primary. The PDFs for sampling photon energy and direction relative to the source long axis, depend on the position of photon emergence. Photons emerge mainly from the cylindrical source surface with a constant probability over +/-0.1 cm from the center of the 0.35 cm long source core, and only 1.7% and 0.2% emerge from the source tip and drive wire, respectively. Based on these findings, an analytical parameterized source model is prepared for the calculation of the PDFs from data of source geometry and materials, without the need for a phsp file. The PDFs from the analytical parameterized source model are in close agreement with those employed in the parameterized phsp source model. This agreement prompted the proposal of a purely analytical source model based on isotropic emission of photons generated homogeneously within the source core with energy sampled from the (192)Ir spectrum, and the assignment of a weight according to attenuation within the source. Comparison of single source dosimetry data obtained from detailed MC simulation and the proposed analytical source model show agreement better than 2% except for points lying close to the source longitudinal axis. PMID- 27191180 TI - Autobiographical memory impairment in obstructive sleep apnea patients with and without depressive symptoms. AB - Obstructive sleep apnea is associated with memory impairments, and higher rates of depressive symptoms and major depressive disorder compared with community estimates. Autobiographical memory overgenerality, a behaviour characterized by difficulty recalling specific memories from one's own life, is recognized as a marker of depression. Previous studies have demonstrated the predictive quality of specific autobiographical memory recall on the course of depression in patients with obstructive sleep apnea. However, it remains unclear whether impaired autobiographical memory is simply a feature of depression, or whether it is also impaired in patients with obstructive sleep apnea without depression. This study aimed to investigate whether autobiographical memory impairments can be observed in patients with obstructive sleep apnea, independent of the severity of depressive symptoms. Twenty-one patients with obstructive sleep apnea symptomatic for depressive symptoms (mean age = 43.43 years, SD = 9.97), 17 patients with obstructive sleep apnea asymptomatic for depressive symptoms (mean age = 40.65 years, SD = 9.39), and 20 healthy controls without sleep-disordered breathing (mean age = 32.80 years, SD = 6.69) completed an Autobiographical Memory Test. Patients with obstructive sleep apnea symptomatic for depressive symptoms recalled significantly fewer specific memories when compared with healthy controls (P = 0.010). No difference in the recall of specific autobiographical memory was observed between symptomatic and asymptomatic patients with obstructive sleep apnea. With regard to valence, symptomatic patients with obstructive sleep apnea recalled significantly fewer negative specific memories when compared with controls (P = 0.010). Impairment in specific autobiographical memory recall can be observed in patients with obstructive sleep apnea, regardless of the severity of depressive symptoms; however, this effect may not be as prominent in younger patients with obstructive sleep apnea. PMID- 27191181 TI - Health impact and noise exposure assessment in the cricket bat industry of Kashmir, India. AB - AIM: The aim of the present study was to identify and evaluate predominant noise sources in the cricket bat industry of Kashmir, India. METHODS: Sound levels were measured at operator's ear level in the working zone of the workers of seven cricket bat factories. The impact assessment was made through personal interviews with each worker separately during their period of rest. RESULTS: On average, 62.5% of the workers reported difficulty in hearing and 24.1% of the workers have become patients for hypertension. Only 58.1% of the workers complained of headache due to high noise level. CONCLUSIONS: The workers engaged in the cricket bat industry of Kashmir are exposed to high noise levels. It is suggested that personal protective equipment like ear plugs and ear muffs be used by these workers as a protection against this hazard. PMID- 27191182 TI - Automated hybrid closed-loop control with a proportional-integral-derivative based system in adolescents and adults with type 1 diabetes: individualizing settings for optimal performance. AB - BACKGROUND: Automated insulin delivery systems, utilizing a control algorithm to dose insulin based upon subcutaneous continuous glucose sensor values and insulin pump therapy, will soon be available for commercial use. The objective of this study was to determine the preliminary safety and efficacy of initialization parameters with the Medtronic hybrid closed-loop controller by comparing percentage of time in range, 70-180 mg/dL (3.9-10 mmol/L), mean glucose values, as well as percentage of time above and below target range between sensor augmented pump therapy and hybrid closed-loop, in adults and adolescents with type 1 diabetes. METHODS: We studied an initial cohort of 9 adults followed by a second cohort of 15 adolescents, using the Medtronic hybrid closed-loop system with the proportional-integral-derivative with insulin feed-back (PID-IFB) algorithm. Hybrid closed-loop was tested in supervised hotel-based studies over 4 5 days. RESULTS: The overall mean percentage of time in range (70-180 mg/dL, 3.9 10 mmol/L) during hybrid closed-loop was 71.8% in the adult cohort and 69.8% in the adolescent cohort. The overall percentage of time spent under 70 mg/dL (3.9 mmol/L) was 2.0% in the adult cohort and 2.5% in the adolescent cohort. Mean glucose values were 152 mg/dL (8.4 mmol/L) in the adult cohort and 153 mg/dL (8.5 mmol/L) in the adolescent cohort. CONCLUSIONS: Closed-loop control using the Medtronic hybrid closed-loop system enables adaptive, real-time basal rate modulation. Initializing hybrid closed-loop in clinical practice will involve individualizing initiation parameters to optimize overall glucose control. PMID- 27191184 TI - Enhanced photoluminescence and phosphorescence properties of green phosphor Zn2GeO4:Mn(2+)via composition modification with GeO2 and MgF2. AB - A green long-lasting phosphorescence (LLP) phosphor Zn2GeO4:Mn(2+) (ZGOM) has been synthesized by a solid-state method at 1100 degrees C in air. The luminescence intensity has been improved up to 9 and 6 times through mixing GeO2 and MgF2 into the composition, respectively. The phosphorescence duration of the sample has been prolonged to 5 h. The phosphor, composed of a mixture of Zn2GeO4 (ZGO), GeO2, and MgGeO3 phases, emits enhanced green luminescence with a broad excitation band between 250 nm to 400 nm. Under identical measurement conditions, the optimized phosphor ZGOM has a higher emission intensity and shows longer wavelength emission than those of the commercial green LLP phosphor SrAl2O4:Eu,Dy (SAOED) under an excitation at 336 nm. The quantum yield of the sample modified by GeO2 and MgF2 is as high as 95.0%. Understanding of the formation mechanism for enhancement of emission intensity and prolonging of phosphorescence duration of ZGOM is fundamentally important, which might be extended to other identified solid-state inorganic phosphor materials for advanced properties. PMID- 27191183 TI - Hollow Structure Improved Anti-Cancer Immunity of Mesoporous Silica Nanospheres In Vivo. AB - Hollow and non-hollow mesoporous silica nanospheres are synthesized and used for cancer vaccine adjuvants. The hollow structure of mesoporous silica nanospheres significantly promote cellular uptake of a model cancer antigen by macrophage like cells in vitro, improve anti-cancer immunity, CD4(+) and CD8(+) T cell populations in splenocytes of mice in vivo. PMID- 27191185 TI - Quantifying Isoniazid Levels in Small Hair Samples: A Novel Method for Assessing Adherence during the Treatment of Latent and Active Tuberculosis. AB - BACKGROUND: Tuberculosis (TB) is the leading cause of death from an infectious pathogen worldwide and the most prevalent opportunistic infection in people living with HIV. Isoniazid preventive therapy (IPT) reduces the incidence of active TB and reduces morbidity and mortality in HIV-infected patients independently of antiretroviral therapy. However, treatment of latent or active TB is lengthy and inter-patient variability in pharmacokinetics and adherence common. Current methods of assessing adherence to TB treatment using drug levels in plasma or urine assess short-term exposure and pose logistical challenges. Drug concentrations in hair assess long-term exposure and have demonstrated pharmacodynamic relevance in HIV. METHODS: A large hair sample from a patient with active TB was obtained for assay development. Methods to pulverize hair and extract isoniazid were optimized and then the drug detected by liquid chromatography/ tandem mass spectrometry (LC/MS-MS). The method was validated for specificity, accuracy, precision, recovery, linearity and stability to establish the assay's suitability for therapeutic drug monitoring (TDM). Hair samples from patients on directly-observe isoniazid-based latent or active TB therapy from the San Francisco Department of Public Health TB clinic were then tested. RESULTS: Our LC/MS-MS-based assay detected isoniazid in quantities as low as 0.02ng/mg using 10-25 strands hair. Concentrations in spiked samples demonstrated linearity from 0.05-50ng/mg. Assay precision and accuracy for spiked quality-control samples were high, with an overall recovery rate of 79.5%. In 18 patients with latent or active TB on treatment, isoniazid was detected across a wide linear dynamic range. CONCLUSIONS: An LC-MS/MS-based assay to quantify isoniazid levels in hair with performance characteristics suitable for TDM was developed and validated. Hair concentrations of isoniazid assess long-term exposure and may be useful for monitoring adherence to latent or active TB treatment in the setting of HIV. PMID- 27191187 TI - Do as I Say, Not as I Do? An Examination of the Relationship Between Partner Behaviors and Help Seeking for Alcohol Related Issues. AB - BACKGROUND: Although there are a number of risks associated with problematic alcohol use, the proportion of people who seek help for alcohol-related issues is alarmingly low. OBJECTIVE: This study investigated the potential social influences that are associated with alcohol-related help seeking, including perceived partner support, descriptive and injunctive subjective norms, and marital satisfaction. METHODS: Participants included 133 individuals (50% female, 48% male, and 2% did not report) recruited nationwide through both print and electronic methods. Data were collected in an online survey in 2013. Respondents were 77% Caucasian, 16% African-American, 2% Asian, 2% American Indian, and 1% Hawaiian/Pacific Islander, with a mean age of 38 years (SD = 11.93). Data were analyzed using hierarchical multiple regression. RESULTS: Results suggested that when considered independently, perceived partner support, injunctive social norms, and closest friend's level of drinking were significantly associated with help seeking behavior, while marital satisfaction was not. Results further indicated that examining support and norms together accounted for increased variance in help seeking over examining the variables separately. Significant interactions were found between gender and acceptance of drinking behavior, which suggested that acceptance of drinking behavior was important for men's help seeking but not for women's, and between positive support and acceptance, which indicated that the role of support varied by level of acceptance for both genders. CONCLUSION: Overall, this study suggests that social influences play an important role in a person's decision to seek help for alcohol related issues. PMID- 27191186 TI - Associations between Parents' Perceived Air Quality in Homes and Health among Children in Nanjing, China. AB - The increasing prevalence of respiratory diseases in Chinese children has focused attention on indoor environmental quality. We investigated associations between perceived air quality in domestic environments and children's allergic diseases with a questionnaire survey study. A total of 4017 children aged 1-8 years old from 23 kindergartens in urban, suburban and industrial areas in Nanjing were randomly recruited for this study. Parents' perceived odors, including stuffy odor, unpleasant odor, pungent odor, moldy odor, humid air and dry air were found to be associated with asthma, wheeze, dry cough and rhinitis (P < 0.05). Both perceived dry and humid air were found to be positively associated with dampness indices, and we present evidence that the sensation of dryness may not be due to the actual indoor relative humidity, but rather to indoor air irritants. Parents' perception of odors and relative humidity may be indicators of environment pollutants, which are likely the real factors associated with children's allergic diseases. PMID- 27191189 TI - Clocking Surface Reaction by In-Plane Product Rotation. AB - Electron-induced reaction of physisorbed meta-diiodobenzene (mDIB) on Cu(110) at 4.6 K was studied by Scanning Tunneling Microscopy and molecular dynamics theory. Single-electron dissociation of the first C-I bond led to in-plane rotation of an iodophenyl (IPh) intermediate, whose motion could be treated as a "clock" of the reaction dynamics. Alternative reaction mechanisms, successive and concerted, were observed giving different product distributions. In the successive mechanism, two electrons successively broke single C-I bonds; the first C-I bond breaking yielded IPh that rotated directionally by three different angles, with the second C-I bond breaking giving chemisorbed I atoms (#2) at three preferred locations corresponding to the C-I bond alignments in the prior rotated IPh configurations. In the concerted mechanism a single electron broke two C-I bonds, giving two chemisorbed I atoms; significantly these were found at angles corresponding to the C-I bond direction for unrotated mDIB. Molecular dynamics accounted for the difference in reaction outcomes between the successive and the concerted mechanisms in terms of the time required for the IPh to rotate in plane; in successive reaction the time delay between first and second C-I bond breaking events allowed the IPh to rotate, whereas in concerted reaction the computed delay between excitation and reaction (~1 ps) was too short for molecular rotation before the second C-I bond broke. The dependence of the extent of motion at a surface on the delay between first and second bond breaking suggested a novel means to "clock" sub-picosecond dynamics by imaging the products arising from varying time delays between impacting pairs of electrons. PMID- 27191190 TI - Family Centered Practice During Pediatric Death in an Out of Hospital Setting. AB - OBJECTIVE: To understand effective ways for EMS providers to interact with distressed family members during a field intervention involving a recent or impending out-of-hospital (OOH) pediatric death. METHODS: Eight focus groups with 98 EMS providers were conducted in urban and rural settings between November 2013 and March 2014. Sixty-eight providers also completed a short questionnaire about a specific event including demographics. Seventy-eight percent of providers were males, 13% were either African American or Hispanic, and the average number of years in EMS was 16 years. They were asked how team members managed the family during the response to a dying child, what was most helpful for families whose child suddenly and unexpectedly was dead in the OOH setting, and what follow up efforts with the family were effective. RESULTS: The professional response by the EMS team was critical to family coping and getting necessary support. There were several critical competencies identified to help the family cope including: (1) that EMS provide excellent and expeditious care with seamless coordination, (2) allowing family to witness the resuscitation including the attempts to save the child's life, and (3) providing ongoing communication. Whether the child is removed from the scene or not, keeping the family appraised of what is happening and why is critical. Exclusion of families from the process in cases of suspected child abuse is not warranted. Giving tangible forms of support by calling friends, family, and clergy, along with allowing the family time with the child after death, giving emotional support, and follow-up gestures all help families cope. CONCLUSION: The study revealed effective ways for EMS providers to interact with distressed family members during an OOH pediatric death. PMID- 27191188 TI - Development of Medical Countermeasures to Middle East Respiratory Syndrome Coronavirus. AB - Preclinical development of and research on potential Middle East respiratory syndrome coronavirus (MERS-CoV) medical countermeasures remain preliminary; advancements are needed before most countermeasures are ready to be tested in human clinical trials. Research priorities include standardization of animal models and virus stocks for studying disease pathogenesis and efficacy of medical countermeasures; development of MERS-CoV diagnostics; improved access to nonhuman primates to support preclinical research; studies to better understand and control MERS-CoV disease, including vaccination studies in camels; and development of a standardized clinical trial protocol. Partnering with clinical trial networks in affected countries to evaluate safety and efficacy of investigational therapeutics will strengthen efforts to identify successful medical countermeasures. PMID- 27191191 TI - Leveraging a faculty fellowship programme to develop leaders in interprofessional education. AB - This article reports findings from an interprofessional education (IPE) study of a longitudinal faculty fellowship that aimed to develop IPE leaders at an academic institution based in the United States. Eight applicants were competitively selected to participate in an IPE track of the fellowship, alongside 14 faculty members who entered through a separate selection process. One year after graduation, a survey of the IPE fellows was undertaken to evaluate programme outcomes using open-ended questions based on an adaptation of Kirkpatrick's four-level training evaluation model. Results indicated that respondents valued participating in a longitudinal programme where they could learn about and practice teaching and leadership skills and conduct education scholarship. While learning on an interprofessional basis, the fellows reported establishing relationships that endured after graduation. This report suggests that adding IPE activities to existing faculty fellowship programmes can be an effective means of building faculty capacity to advance institutional IPE initiatives. PMID- 27191193 TI - Isolation, purification, and partial characterization of a membrane-bound Cl /HCO3--activated ATPase complex from rat brain with sensitivity to GABAAergic ligands. AB - This study describes the isolation and purification of a protein complex with [Formula: see text]-ATPase activity and sensitivity to GABAAergic ligands from rat brain plasma membranes. The ATPase complex was enriched using size-exclusion, affinity, and ion-exchange chromatography. The fractions obtained at each purification step were subjected to SDS-polyacrylamide gel electrophoresis (SDS PAGE), which revealed four subunits with molecular mass ~48, 52, 56, and 59 kDa; these were retained at all stages of the purification process. Autoradiography revealed that the ~52 and 56 kDa subunits could bind [3H]muscimol. The [Formula: see text]-ATPase activity of this enriched protein complex was regulated by GABAAergic ligands but was not sensitive to blockers of the NKCC or KCC cotransporters. PMID- 27191194 TI - Functional characterization of the ABCG2 5' non-coding exon variants: Stem cell specificity, translation efficiency and the influence of drug selection. AB - ABCG2 is a multidrug transporter with wide substrate specificity, and is believed to protect several cell types from various xenobiotics and endobiotics. This "guardian" function is important in numerous cell types and tissue barriers but becomes disadvantageous by being responsible for the multidrug resistance phenotype in certain tumor cells. ABCG2 regulation at the protein level has already been extensively studied, however, regulation at the mRNA level, especially the functional role of the various 5' untranslated exon variants (5' UTRs) has been elusive. In the present work, we describe a comprehensive characterization of four ABCG2 mRNA variants with different exon 1 sequences, investigate drug inducibility, stem cell specificity, mRNA stability, and translation efficiency. Although certain variants (E1B and E1C) are considered as "constitutive" mRNA isoforms, we show that chemotoxic drugs significantly alter the expression pattern of distinct ABCG2 mRNA isoforms. When examining human embryonic stem cell lines, we provide evidence that variant E1A has an expression pattern coupled to undifferentiated stem cell stage, as its transcript level is regulated parallel to mRNAs of Oct4 and Nanog pluripotency marker genes. When characterizing the four exon 1 variants we found no significant differences in terms of mRNA stabilities and half-lives of the isoforms. In contrast, variant E1U showed markedly lower translation efficiency both at the total protein level or regarding the functional presence in the plasma membrane. Taken together, these results indicate that the different 5' UTR variants play an important role in cell type specific regulation and fine tuning of ABCG2 expression. PMID- 27191192 TI - Genetic and clinical features of cryopyrin-associated periodic syndromes in Turkish children. AB - OBJECTIVES: The aim of this study was to present the genetic and clinical data of the largest cohort of Turkish cryopyrin-associated periodic syndromes (CAPS) patients. METHODS: This is a two-centre descriptive study of Turkish children with clinical diagnosis of CAPS. NLRP3 analyses were performed by Sanger sequencing and by massively parallel sequencing. ASC dependent NF-kappaB activation and transfection-induced THP-1 cell death assays determined the functional consequences of the detected variants. Disease activity and response to anti interleukin 1 (anti-IL-1) treatment was also assessed. RESULTS: Heterozygous germline NLRP3 mutation was detected in 8 of 14 enrolled patients (57.1%). Two novel somatic mutations Y560H and G307D were found which induced both THP-1 cell death and ASC dependent NF-kB activation. With anti-IL-1 treatment the disease activity was improved in all patients except one. Except two patients with macrophage activation syndrome (MAS) attack, there were no serious adverse events requiring hospitalisation. CONCLUSIONS: CAPS should be considered in all patients with typical symptoms even if Sanger-based genetic analysis is negative, since a considerable number of patients have mosaicism. Treatment should be patient-tailored and MAS should be considered as a rare complication. PMID- 27191196 TI - Response to Kaya and Yildirim's Letter: "Choroidal Thinning May Change Scleral Architecture". PMID- 27191195 TI - Skeletal site-specific effects of endurance running on structure and strength of tibia, lumbar vertebrae, and mandible in male Sprague-Dawley rats. AB - Bone microarchitecture, bone mineral density (BMD), and bone strength are affected positively by impact activities such as running; however, there are discrepancies in the magnitude of these effects. These inconsistencies are mainly a result of varying training protocols, analysis techniques, and whether or not the skeletal sites measured are weight bearing. This study's purpose was to determine the effects of endurance running on sites that experience different weight bearing and load. Eight-week-old male Sprague-Dawley rats (n = 20) were randomly assigned to either a group with a progressive treadmill running protocol (25 m/min for 1 h, incline of 10%) or a nontrained control group for 8 weeks. The trabecular structure of the tibia, lumbar vertebra (L3), and mandible and the cortical structure at the tibia midpoint were measured using microcomputed tomography to quantify bone volume fraction (i.e., bone volume divided by total volume (BV/TV)), trabecular number (Tb.N), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), and cortical thickness. BMD at the proximal tibia, lumbar vertebrae (L1-L3), and mandible was measured using dual energy X-ray absorptiometry. The tibia midpoint strength was measured by 3-point bending using a materials testing system. Endurance running resulted in superior bone structure at the proximal tibia (12% greater BV/TV (p = 0.03), 14% greater Tb.N (p = 0.01), and 19% lower Tb.Sp (p = 0.05)) but not at other sites. Contrary to our hypothesis, mandible bone structure was altered after endurance training (8% lower BV/TV (p < 0.01) and 15% lower Tb.Th (p < 0.01)), which may be explained by a lower food intake, resulting in less mechanical loading from chewing. These results highlight the site-specific effects of loading on the skeleton. PMID- 27191197 TI - Imaging Nuclei of MDA-MB-231 Breast Cancer Cells by Chiral Ruthenium(II) Complex Coordinated by 2-(4-Phenyacetylenephenyl)-1H-imidazo[4,5f][1,10]phenanthroline. AB - A pair of chiral ruthenium(II) complexes, Lambda- and Delta-[Ru(bpy)2(p BEPIP)](ClO4)2 [Lambda- and Delta-RM0627; bpy = 2,2-bipyridine; p-BEPIP = 2-(4 phenyacetylenephenyl)-1H-imidazo[4,5f][1,10]phenanthroline], were prepared using the Sonogashira coupling reaction under microwave irradiation. The study shows that Lambda-RM0627 emitted strong phosphorescence in the range 500-700 nm with a maximum at 594 nm when excited at 365 nm (the Stokes shift is about 227 nm), which was mainly located in the cell nucleus with red phosphorescence. Further studies using real-time phosphorescence observation confirmed that Lambda-RM0627 can be taken up quickly by MDA-MB-231 cells and enriched in the nucleus. The in vitro and in vivo toxicities of Lambda-RM0627 were also evaluated, and it was found that Lambda-RM0627 slightly inhibited the growth of MDA-MB-231 breast cancer cells and HaCaT normal human epidermal cells and had little influence on the development of Zebrafish embryos at low concentration. In conclusion, the levoisomer of chiral ruthenium complexes can act as a potential phosphorescent probe that targets nuclei of living cells with low toxicity. PMID- 27191198 TI - Highly Enantioselective Formation of alpha-Allyl-alpha-Arylcyclopentanones via Pd Catalysed Decarboxylative Asymmetric Allylic Alkylation. AB - A highly enantioselective Pd-catalysed decarboxylative asymmetric allylic alkylation of cyclopentanone derived alpha-aryl-beta-keto esters employing the (R,R)-ANDEN-phenyl Trost ligand has been developed. The product (S)-alpha-allyl alpha-arylcyclopentanones were obtained in excellent yields and enantioselectivities (up to >99.9 % ee). This represents one of the most highly enantioselective formations of an all-carbon quaternary stereogenic center reported to date. This reaction was demonstrated on a 4.0 mmol scale without any deterioration of enantioselectivity and was exploited as the key enantioselective transformation in an asymmetric formal synthesis of the natural product (+) tanikolide. PMID- 27191200 TI - The role of multiplex molecular panels for the diagnosis of gastrointestinal infections in immunocompromised patients. AB - PURPOSE OF REVIEW: An increasing number of laboratories have implemented multiplex molecular panels for the diagnosis of gastrointestinal infections. This review focuses on recent data addressing the performance of US Food and Drug Administration-cleared multiplex gastrointestinal panels and discusses the advantages and limitations of these tests in the immunocompromised population. RECENT FINDINGS: Testing for gastrointestinal pathogens using multiplex molecular panels increases sensitivity and detection of coinfections compared with routine testing methods. Furthermore, multiplex panels reduce turnaround time and may allow for more informed decisions regarding treatment and infection control measures. However, the routine use of multiplex gastrointestinal panels has led to an increase in the detection of certain organisms, such as enteroaggregative Escherichia coli and sapovirus, which many clinical laboratories did not specifically test for in the past. This has created a degree of confusion on how to best interpret the results of multiplex panels, especially in the immunocompromised host. SUMMARY: Multiplex molecular panels provide a rapid and sensitive tool for the diagnosis of infectious diarrhea, and may allow for more timely decisions regarding the management of immunosuppressed patients. However, there are limitations associated with multiplex panels, including the interpretation of results and the cost associated with testing. Clinical microbiologists should work closely with clinicians to develop evidence-based algorithms to guide test utilization in this area. PMID- 27191199 TI - Treatment of mucormycosis in transplant patients: role of surgery and of old and new antifungal agents. AB - PURPOSE OF REVIEW: Mucormycosis is an opportunistic mold infection whose management is difficult, as there is a paucity of evidence-based data. We summarize the latest advances in diagnosis and management of mucormycosis in transplant recipients. RECENT FINDINGS: There is promise for improvement in nonculture-based diagnostics with new biomarkers of Mucorales DNA that can be used for early diagnosis, and monitoring of response. Antifungal treatment consists of high-dose lipid formulations of amphotericin B or isavuconazole as the first-line therapy and posaconazole as salvage therapy. The new, pharmacokinetically more reliable formulations of posaconazole (intravenous, extended-release tablets) are welcomed improvements. Yet, the role of combination therapy is still uncertain. Surgery had a significant role in selected cases, such as in patients with rhinosinusitis form of mucormycosis, which nowadays can be performed with minimal invasive technique. SUMMARY: Mucormycosis remain a life threatening opportunistic mold infection among transplant patients. Early diagnosis, prompt treatment with effective antifungals in combination with surgery if feasible is essential. Immune adjunct therapy and improvement of early diagnostics are important areas for future research. There are good prospects of progress in diagnostics and management of mucormycosis in transplant patients. PMID- 27191201 TI - Molecular diagnosis of toxoplasmosis in immunocompromised patients. AB - PURPOSE OF REVIEW: Toxoplasmosis in immunocompromised patients is associated with a high mortality rate. Molecular techniques are important tools to diagnose acute disease in immunocompromised patients, but there are various methods with variable efficiency. Some of them have been validated for the diagnosis of congenital toxoplasmosis, but the impact of their use has not been evaluated in immunocompromised patients. RECENT FINDINGS: Toxoplasmosis is of increasing importance in non-HIV immunocompromised patients. In addition, the picture of disease shows greater severity in South America, both in immunocompetent study participants and in congenitally infected infants. These epidemiological differences could influence the sensitivity of diagnostic methods. This review analyzes recent data on molecular diagnosis and compares them with older ones, in light of progress gained in molecular techniques and of recent epidemiological findings. Most recent studies were conducted in South America and used PCR targeting the B1 gene. PCR on blood could allow diagnosing a significant proportion of patients with ocular toxoplasmosis in Brazil. SUMMARY: Quantitative PCR methods with specific probes should be used to improve sensitivity and warrant specificity. Performance of quantitative PCR targeting the repeated 529 bp sequence for the diagnosis of toxoplasmosis in immunocompromised patients needs evaluation in field studies in South America and in western countries. PMID- 27191202 TI - Hepatitis C following liver transplantation: current approach and future research opportunities. AB - PURPOSE OF REVIEW: The treatment of hepatitis C virus infection (HCV) in liver transplant recipients was very limited until direct-acting antivirals became widely available. We review the current approach to HCV treatment following liver transplantation and future research opportunities. RECENT FINDINGS: Current treatment of HCV infection with all oral new direct-acting antivirals in the postliver transplant setting is easier, shorter, tolerable, and more effective with high-sustained virological response rates. However, some challenges remain, including the optimal timing of therapy, drug-drug interactions, renal insufficiency, and HIV coinfection. SUMMARY: Patients with recurrent HCV following liver transplant will significantly benefit from all oral new direct acting antivirals. Ongoing studies will determine the optimal timing and combination in this unique population. PMID- 27191203 TI - Cryptococcus gattii VGIIb-like Variant in White-Tailed Deer, Nova Scotia, Canada. PMID- 27191204 TI - A Mixed Model to Disentangle Variance and Serial Autocorrelation in Affective Instability Using Ecological Momentary Assessment Data. AB - Affective instability, the tendency to experience emotions that fluctuate frequently and intensively over time, is a core feature of several mental disorders including borderline personality disorder. Currently, affect is often measured with Ecological Momentary Assessment protocols, which yield the possibility to quantify the instability of affect over time. A number of linear mixed models are proposed to examine (diagnostic) group differences in affective instability. The models contribute to the existing literature by estimating simultaneously both the variance and serial dependency component of affective instability when observations are unequally spaced in time with the serial autocorrelation (or emotional inertia) declining as a function of the time interval between observations. In addition, the models can eliminate systematic trends, take between subject differences into account and test for (diagnostic) group differences in serial autocorrelation, short-term as well as long-term affective variability. The usefulness of the models is illustrated in a study on diagnostic group differences in affective instability in the domain of eating disorders. Limitations of the model are that they pertain to group (and not individual) differences and do not focus explicitly on circadian rhythms or cycles in affect. PMID- 27191205 TI - Anticorps Monoclonaux: Principes Fondamentaux Et Applications. AB - The technique of hybridization of myeloma and B-lymphoid cells synthetizing antibodies, allows to obtain cellular clones producing a pre-defined antibody, during an undefined time and in unlimited quantity. The monoclonal antibodies have analytical properties which have never been obtained until now. They also constitute a major progress in the production of antisera, allowing their standardization, not only of place (unlimited production) but of time, thanks to the immortality (at least in principle) of the hybridoma clones. Finally, they represent a possible revival of serotherapy. PMID- 27191207 TI - Same-Sex Couples' Decisions and Experiences of Marriage in the Context of Minority Stress: Interviews From a Population-Based Longitudinal Study. AB - In the emerging context of marriage equality, it is important to explore the reasons for and experience of marriage for long-term same-sex couples, including the role of minority stress. In Wave 3 of the population-based, longitudinal CUPPLES Study we interviewed 21 long-term same-sex couples (14 female, 7 male) who resided in 12 different states and who were legally married. Couple members ranged in age from 37 to 84 and reported being together as a couple from 15 to 41 years. Seven couples lived in states that did not recognize their marriage at the time of the interview. Legal protection and social validation emerged as the two primary domains that captured couples' lived experiences of marriage. Minority stress experiences emerged in the narratives in the context of couples' long-term commitment, the availability of civil marriage, and couples' participation in activist efforts on behalf of marriage equality for themselves and others. PMID- 27191208 TI - Inflammatory Bowel Disease Patients' Participation, Attitude and Preferences Toward Exercise. AB - The purpose of the study was to investigate the level of exercise participation in patients with inflammatory bowel disease (IBD) and to investigate their intention, attitude and preference toward exercise. The data of 158 IBD patients that participated in a self-administered survey at Severance Hospital between March 2013 and November 2013 were included in this cross sectional and descriptive analysis. Questionnaires included 3 sections to determine the IBD patient's current exercise participation, attitude toward exercise, and exercise preferences. This study investigated IBD patients both collectively, and according to their specific disease: Crohn's disease (CD) (n=62), Ulcerative colitis (UC) (n=73) and intestinal Behcet's disease (BD) (n=23). IBD patients currently participate in 103 min/week of exercise including mild, moderate and strenuous intensity, with BD patients being the least active, followed by CD, and UC being most active. The majority of IBD patients found exercise to be pleasant (57.7%), beneficial (80.5%), sensible (71.8%), uplifting (61%) and good (70.5%), and 44.4% found exercise to be enjoyable. This study shows the IBD patients' participation, attitude and preferences toward exercise and provides much needed information for the development of evidence based exercise programs that are specific to IBD. PMID- 27191209 TI - A Preliminary Exploration of Concussion and Strength Performance in Youth Ice Hockey Players. AB - The objective of this study was to describe the effect of concussion on upper and lower body strength in children and youth athletes. The participant group was made up of 178 unique male and female ice hockey players (ages 8-14 years). Using a 3-year prospective longitudinal research design, baseline and post-concussion data on hand grip strength, jump tests, and leg maximal voluntary contraction were collected. Using a linear mixed-effects model, no significant differences were found when comparing the baseline strength performance of individuals who went on to experience a concussion and those who did not. When accounting for sex, multiple concussions, and ongoing changes in strength associated with age, weaker hand grip scores were found following concussion while participants were still symptomatic. Lower squat jump heights were achieved while participants were symptomatic as well as when they were no longer self-reporting symptoms associated with concussion. This study represents an initial step towards better understanding strength performance following concussion that may limit the on and off ice performance of youth ice hockey players, as well as predispose youth to subsequent injuries. PMID- 27191210 TI - The Effect of Inspiratory Muscle Training on Respiratory and Limb Locomotor Muscle Deoxygenation During Exercise with Resistive Inspiratory Loading. AB - We investigated how inspiratory muscle training impacted respiratory and locomotor muscle deoxygenation during submaximal exercise with resistive inspiratory loading. 16 male cyclists completed 6 weeks of either true (n=8) or sham (n=8) inspiratory muscle training. Pre- and post-training, subjects completed 3, 6-min experimental trials performed at ~80% VO2peak with interventions of either moderate inspiratory loading, heavy inspiratory loading, or maximal exercise imposed in the final 3 min. Locomotor and respiratory muscle oxy-, deoxy-, and total-haemoglobin and myoglobin concentration was continuously monitored using near-infrared spectroscopy. Locomotor muscle deoxygenation changes from 80% VO2peak to heavy inspiratory loading were significantly reduced pre- to post-training from 4.3+/-5.6 uM to 2.7+/-4.7 uM. Respiratory muscle deoxygenation was also significantly reduced during the heavy inspiratory loading trial (4.6+/-3.5 uM to 1.9+/-1.5 uM) post-training. There was no significant difference in oxy-, deoxy-, or total-haemoglobin and myoglobin during any of the other loading trials, from pre- to post-training, in either group. After inspiratory muscle training, highly-trained cyclists exhibited decreased locomotor and respiratory muscle deoxygenation during exercise with heavy inspiratory loading. These data suggest that inspiratory muscle training reduces oxygen extraction by the active respiratory and limb muscles, which may reflect changes in respiratory and locomotor muscle oxygen delivery. PMID- 27191211 TI - Do Stretch Durations Affect Muscle Mechanical and Neurophysiological Properties? AB - The aim of the study was to determine whether stretching durations influence acute changes of mechanical and neurophysiological properties of plantar flexor muscles. Plantar flexors of 10 active males were stretched in passive conditions on an isokinetic dynamometer. Different durations of static stretching were tested in 5 randomly ordered experimental trials (1, 2, 3, 4 and 10*30-s). Fascicle stiffness index, evoked contractile properties and spinal excitability (Hmax/Mmax) were examined before (PRE), immediately after (POST0) and 5 min after (POST5) stretching. No stretch duration effect was recorded for any variable. Moreover, whatever the stretching duration, stiffness index, peak twitch torque and rate of force development were significantly lower at POST0 and POST5 as compared to PRE (P<0.05). Electromechanical delay was longer at POST0 and POST5 as compared to PRE (P<0.05). Whatever the stretch duration, no significant changes of Hmax/Mmax ratio were recorded. In conclusion, 30 s of static stretching to maximum tolerated discomfort is sufficient enough to alter mechanical properties of plantar flexor muscles, but 10*30 s does not significantly affect these properties further. Stretching does not impair spinal excitability. PMID- 27191212 TI - The Neuropsychology of Working Memory: An Introduction. PMID- 27191213 TI - Working Memory: A Selective Review. AB - The purpose of this paper is to provide a selective overview of the evolution of the concept and assessment of working memory, and how its assessment has been confused with the assessment of some components of attention. A literature search using PsychNet Gold was conducted using the terms working memory. In addition, the writer reviewed recommendations from a sampling of recent neuropsychology texts in regard to the assessment of attention and working memory, as well as the two most recent editions of the Wechsler Memory Scale. It is argued that many clinicians have an incomplete understanding of the relationship between attention and working memory, and often conflate the two in assessment and treatment. Suggestions were made for assessing these abilities. PMID- 27191214 TI - Parental Perceptions of the Efficacy of Cogmed Working Memory Training. AB - Many articles have been written about the effectiveness of Cogmed Working Memory Training (CWMT). As Cogmed licensees, we have provided CWMT to more than 350 trainees and have collected pre- and post-training assessment data and parental feedback from about 280 child and adolescent trainees and their parents. On all nine measures of working memory and other selected executive functions, we have found statistically significant improvement. We also offer many of the comments and feedback that we have received from families about the changes they have experienced. There are limitations to the one group pre-test post-test design used in this study that need to be considered as the results are reviewed. PMID- 27191215 TI - Working Memory in the Classroom: An Inside Look at the Central Executive. AB - This article provides a review of working memory and its application to educational settings. A discussion of the varying definitions of working memory is presented. Special attention is given to the various multidisciplinary professionals who work with students with working memory deficits, and their unique understanding of the construct. Definitions and theories of working memory are briefly summarized and provide the foundation for understanding practical applications of working memory to assessment and intervention. Although definitions and models of working memory abound, there is limited consensus regarding universally accepted definitions and models. Current research indicates that developing new models of working memory may be an appropriate paradigm shift at this time. The integration of individual practitioner's knowledge regarding academic achievement, working memory and processing speed could provide a foundation for the future development of new working memory models. Future directions for research should aim to explain how tasks and behaviors are supported by the substrates of the cortico-striatal and the cerebro-cerebellar systems. Translation of neurobiological information into educational contexts will be helpful to inform all practitioners' knowledge of working memory constructs. It will also allow for universally accepted definitions and models of working memory to arise and facilitate more effective collaboration between disciplines working in educational setting. PMID- 27191216 TI - Working Memory Goes to School. AB - This article endeavors to provide a comprehensive developmental perspective of Working Memory in the classroom. Instructional implications will be discussed as they apply to preschool, elementary and secondary education. It is the intent of this paper to also provide food for thought about working memory as it applies to other aspects of the school day, such as physical education and social, emotional, and behavioral functioning. PMID- 27191217 TI - Neuro-Cognitive Intervention for Working Memory: Preliminary Results and Future Directions. AB - Definitions of working memory identify it as a function of the executive function system in which an individual maintains two or more pieces of information in mind and uses that information simultaneously for some purpose. In academics, working memory is necessary for a variety of functions, including attending to the information one's teacher presents and then using that information simultaneously for problem solving. Research indicates difficulties with working memory are observed in children with mathematics learning disorder (MLD) and reading disorders (RD). To improve working memory and other executive function difficulties, and as an alternative to medication treatments for attention and executive function disorders, the Motor Cognition(2)(r) (MC(2)(r))program was developed. Preliminary research on this program indicates statistically significant improvements in working memory, mathematics, and nonsense word decoding for reading. Further research on the MC(2)(r) program and its impact on working memory, as well as other areas of executive functioning, is warranted. PMID- 27191220 TI - Treating Working Memory Deficits: Current Status, Applications, and Future Directions. PMID- 27191218 TI - Working Memory and Neurofeedback. AB - Impairments in working memory are typically associated with impairments in other cognitive faculties such as attentional processes and short-term memory. This paper briefly introduces neurofeedback as a treatment modality in general, and, more specifically, we review several of the current modalities successfully used in neurofeedback (NF) for the treatment of working memory deficits. Two case studies are presented to illustrate how neurofeedback is applied in treatment. The development of Low Resolution Electromagnetic Tomography (LORETA) and its application in neurofeedback now makes it possible to specifically target deep cortical/subcortical brain structures. Developments in neuroscience concerning neural networks, combined with highly specific yet practical NF technologies, makes neurofeedback of particular interest to neuropsychological practice, including the emergence of specific methodologies for treating very difficult working memory (WM) problems. PMID- 27191219 TI - Implicit Working Memory: Implications for Assessment and Treatment. AB - Working memory (WM) impacts a gamut of cognitive abilities, but implicit WM is typically not considered in assessment or treatment, which may explain the variability of results in reviews of WM training. The role of implicit WM in adaptive behavior is reviewed. All we do is action based. Explicit WM plays a major role when we are required to "think"; that is, when we apply previously learned perception-action linkages in new ways to unique situations. Implicit WM is involved in the automation of behavior, which occurs through interaction with cortical and subcortical systems that guide sensory-motor anticipation and the prediction of reward. This article reviews evidence that implicit WM interacts with cortical-cerebellar and cortical-basal ganglia connections to form perception-action linkages. The cerebellum forms an internal model of cortical WM, corrects the content of this internal model, and then projects the improved representation back to the cortex, where it is retained for future use. The basal ganglia also form an anticipatory system, controlling cortical access to WM by allowing or restricting the information that is released based on the probability of reward. This framework is applied to the assessment and treatment of individuals with WM deficits. The ability to automate behavior can be assessed through repeated trials of existing testing instruments, such as the Trails B and Stroop tasks. Application of skill learning emphasizing automation as an end goal offers a model for the development of new types of WM training. PMID- 27191221 TI - The Differential Effects of Chaplain Interventions on Patient Satisfaction. AB - There is an acute need to define the specific skills that make chaplains integral to the healthcare team. This prospective study attempts to identify those skills that may be specific to chaplains, for whom no other member of the health care team has similar training, and to examine if these skills have a differential effect on patient satisfaction. A total of 59 interventions were identified and grouped into 10 categories by focus groups comprised of chaplains. Subsequently, Principal Component Analysis yielded two independent variables; Component 1 representing the "Religious/Spiritual" dimension, and Component 2 representing the "Psychosocial" dimension of chaplains' work. The two components were used in an OLS regression model to measure patient satisfaction. Interventions that comprise the "Religious/Spiritual" dimension may be considered to be specific skills that chaplains contribute to patient care and these have a slightly stronger correlation with patient satisfaction than the interventions of the "Psychosocial" dimension. PMID- 27191222 TI - Cell-Targeting Cationic Gene Delivery System Based on a Modular Design Rationale. AB - En route to target cells, a gene carrier faces multiple extra- and intracellular hurdles that would affect delivery efficacy. Although diverse strategies have been proposed to functionalize gene carriers for individually overcoming these barriers, it is challenging to generate a single multifunctional gene carrier capable of surmounting all these barriers. Aiming at this challenge, we have developed a supramolecular modular approach to fabricate a multifunctional cationic gene delivery system. It consists of two prefunctionalized modules: (1) a host module: a polymer (PCD-SS-PDMAEMA) composed of poly(beta-cyclodextrin) backbone and disulfide-linked PDMAEMA arms, expectedly acting to compact DNA and release DNA upon cleavage of disulfide linkers in reductive microenvironment; and (2) a guest module: adamantyl and folate terminated PEG (Ad-PEG-FA), expectedly functioning to reduce nonspecific interactions, improve biocompatibility, and provide folate-mediated cellular targeting specificity. Through the host-guest interaction between beta-cyclodextrin units of the "host" module and adamantyl groups of the "guest" module, the PCD-SS-PDMAEMA-1 (host) and Ad-PEG-FA (guest) self-assemble forming a supramolecular pseudocopolymer (PCD-SS-PDMAEMA-1/PEG-FA). Our comprehensive analyses demonstrate that the functions preassigned to the two building modules are well realized. The gene carrier effectively compacts DNA into stable nanosized polyplexes resistant to enzymatic digestion, triggers DNA release in reducing environment, possesses significantly improved hemocompatibility, and specifically targets folate-receptor positive cells. Most importantly, endowed with these predesigned functions, the PCD-SS-PDMAEMA-1/PEG FA supramolecular gene carrier exhibits excellent transfection efficacy for both pDNA and siRNA. Thus, this work represents a proof-of-concept example showing the efficiency and convenience of an adaptable, modular approach for conferring multiple functions to a single supramolecular gene carrier toward effective in vivo delivery of therapeutic nucleic acids. PMID- 27191223 TI - Reemergence of Dengue in Southern Texas, 2013. AB - During a dengue epidemic in northern Mexico, enhanced surveillance identified 53 laboratory-positive cases in southern Texas; 26 (49%) patients acquired the infection locally, and 29 (55%) were hospitalized. Of 83 patient specimens that were initially IgM negative according to ELISA performed at a commercial laboratory, 14 (17%) were dengue virus positive by real-time reverse transcription PCR performed at the Centers for Disease Control and Prevention. Dengue virus types 1 and 3 were identified, and molecular phylogenetic analysis demonstrated close identity with viruses that had recently circulated in Mexico and Central America. Of 51 household members of 22 dengue case-patients who participated in household investigations, 6 (12%) had been recently infected with a dengue virus and reported no recent travel, suggesting intrahousehold transmission. One household member reported having a recent illness consistent with dengue. This outbreak reinforces emergence of dengue in southern Texas, particularly when incidence is high in northern Mexico. PMID- 27191224 TI - Wastewater Treatment Works (WwTW) as a Source of Microplastics in the Aquatic Environment. AB - Municipal effluent discharged from wastewater treatment works (WwTW) is suspected to be a significant contributor of microplastics (MP) to the environment as many personal care products contain plastic microbeads. A secondary WwTW (population equivalent 650 000) was sampled for microplastics at different stages of the treatment process to ascertain at what stage in the treatment process the MP are being removed. The influent contained on average 15.70 (+/-5.23) MP.L(-1). This was reduced to 0.25 (+/-0.04) MP.L(-1) in the final effluent, a decrease of 98.41%. Despite this large reduction we calculate that this WwTW is releasing 65 million microplastics into the receiving water every day. A significant proportion of the microplastic accumulated in and was removed during the grease removal stage (19.67 (+/-4.51) MP/2.5 g), it was only in the grease that the much publicised microbeads were found. This study shows that despite the efficient removal rates of MP achieved by this modern treatment plant when dealing with such a large volume of effluent even a modest amount of microplastics being released per liter of effluent could result in significant amounts of microplastics entering the environment. This is the first study to describe in detail the fate of microplastics during the wastewater treatment process. PMID- 27191225 TI - Rapamycin slows down gut aging. PMID- 27191226 TI - Pregnancy and primary Sjogren's syndrome: management and outcomes in a multicentre retrospective study of 54 pregnancies. AB - OBJECTIVES: Primary Sjogren's syndrome (pSS) is one of the most common autoimmune diseases, mainly affecting women during the fourth decade of life. During pregnancy, the presence of anti-Ro/SSa and anti-La/SSb antibodies increases the risk of congenital heart block (CHB). Foetal and pregnancy outcomes in pregnant women with pSS compared with the general population are difficult to evaluate because of confounding factors including age and body mass index (BMI). METHOD: The aim of this case-control study was to analyse the impact of pSS in pregnant women on foetal and pregnancy outcomes. RESULTS: We enrolled 19 women with pSS (54 pregnancies) matched by age and BMI to 216 controls. Patients with pSS delivered significantly earlier (38 weeks + 3 days vs. 39 weeks + 2 days) and experienced more spontaneous abortions [< 22 weeks of gestation (WG)] than the controls [n = 16/54 (30.0%) vs. n = 1/216 (0.4%); p < 0.00001]. Preterm delivery (<= 37+6 WG) was significantly higher in the pSS group than in the control group (29% vs. 12%, p = 0.04). pSS activity significantly affected the birthweight percentile, which was lower in pregnancies occurring after the diagnosis of pSS than in those occurring before (32.43 +/- 21.57 vs. 60.46 +/- 27.37; p = 0.008). No case of CHB was observed. CONCLUSIONS: pSS is responsible for an increased risk of spontaneous abortion. The duration of pregnancy is lower in patients with than without pSS, with more premature deliveries. Pregnancies that occur after the onset of the disease result in lower birthweight percentile children than when pSS is not clinically overt. PMID- 27191227 TI - tert-Butyl Nitrite: Organic Redox Cocatalyst for Aerobic Aldehyde-Selective Wacker-Tsuji Oxidation. AB - An aldehyde-selective aerobic Wacker-Tsuji oxidation is developed. Using tert butyl nitrite as a simple organic redox cocatalyst instead of copper or silver salts, a variety of aldehydes were achieved as major products in up to 30/1 regioselectivity as well as good to high yields at room temperature. PMID- 27191229 TI - Chronic pain and cognition. PMID- 27191230 TI - Cognitive deficits in chronic pain patients, in a brief screening test, are independent of comorbidities and medication use. AB - Objective To describe and analyze cognitive aspects in patients with chronic pain and a control group without pain. Method A case-control study was conducted on 45 patients with chronic pain and on 45 control subjects. Data including pain diagnosis, comorbidities and medication used, were evaluated. Cognitive tests, such as the Montreal Cognitive Assessment (MoCA), Verbal Fluency Test, Clock Drawing Test and Stroop Test, were applied. Results Patients with chronic pain showed a poorer performance, as shown by the scores of the MoCA test (p < 0.002), Verbal Fluency Test (p < 0.001), Clock Drawing Test (p = 0.022) and Stroop Test (p < 0.000). Chronic pain variable (p = 0.015, linear regression model) was an independent factor for results obtained with the MoCA. Conclusion Patients with chronic pain showed a poorer performance in a brief screening test for cognitive impairment not related to confounding variables, as comorbidities and pain medication use. PMID- 27191231 TI - A histomorphometric study of unmyelinated fibers of the fibular nerve in Wistar rats. AB - There are few histomorphometric studies on the unmyelinated fibers of the fibular nerve in rats, and the number of experimental studies using this nerve has been increasing in the last years. Sixty-two percent of the endoneurial area from 10 fibular nerves of adult Wistar rats was scanned by electron microscopy, and digitized. The total number of unmyelinated axons (1.882 +/- 271) was significantly lesser, and their axon diameters (0.2 um to 2.8 um) significantly higher than that determined in previous studies. The histogram peaked at 1 um. The differences could be due to the nerve sampled area, the number and the age of the animals evaluated, and the laboratory techniques used. This study brings new and referential data to be used in experimental investigations involving histomorphometric evaluation of the rat fibular nerve. PMID- 27191232 TI - Exclusive bed for thrombolysis. A simple measure that allows 85% of ischemic stroke patients to be treated in the first hour. AB - The door-to-needle time is an important goal to reduce the time to treatment in intravenous thrombolysis. Objective Analyze if the inclusion of an exclusive thrombolytic bed reduces the door-to-needle time. Method One hundred and fifty patients admitted for neurological evaluation with ischemic stroke were separated in two groups: in the first, patients were admitted in the Emergency Room for intravenous thrombolysis (ER Group); in the second, patients were admitted in an exclusive thrombolytic bed in the general neurology ward (TB Group). Results Sixty-eight (86.0%) patients from TB Group were treated in the first 60 minutes of arrival as compared to 48 (67.6%) in the ER Group (p = 0.011). Conclusion The introduction of a thrombolytic bed in a general hospital setting can markedly reduce the door-to-needle time, allowing more than 85% of patients to be treated within the first hour of admission. PMID- 27191233 TI - Consistent declining trends in stroke mortality in Brazil: mission accomplished? AB - Stroke mortality rates are declining in Brazil, but diferences among regions need to be better investigated. The age-adjusted stroke mortality trends among adults (30-69 years-old) from Brazilian regions were studied between 1996 and 2011. Method Data were analyzed after: 1) reallocation of deaths with non-registered sex or age; 2) redistribution of garbage codes and 3) underreporting correction. A linear regression model with autoregressive errors and a state space model were fitted to the data, aiming the estimation of annual trends at every point in time. Results Although there were high values, a steady decrease of rates was observed. The decreasing trends among all regions were statistically significant, with higher values of decline among the Northeast and Northern regions, where rates were the highest. Conclusion Standardized methodology use is mandatory for correct interpretation of mortality estimates. Although declining, rates are still extremely high and efforts must be made towards prevention of stroke incidence, reduction of case-fatality rates and prevention of sequelae. PMID- 27191234 TI - The extended pterional approach allows excellent results for removal of anterior cranial fossa meningiomas. AB - Objective To describe a unique operative strategy, instead the classical pterional approach, and to analyses it safety and effectiveness for removal of anterior cranial fossa meningiomas. Method We identify 38 patients with tuberculum sellae and olphactory groove meningiomas operated between 1986 and 2013. Medical charts, operative reports, imaging studies and clinical follow-up evaluations were reviewed and analyzed retrospectively. The pterional craniotomy is extended toward the frontal bone providing access through the subfrontal route, besides the usual anterolateral view provided by the classical pterional approach. Results Surgical mortality occurred in one patient (2.6%). Gross total resection was achieved in 27 patients (86.8%). Median time of follow-up was 69.4 months. Conclusion The extended pterional approach allows excellent results. Total removal of meningiomas of the anterior cranial fossa was obtained in 86.8 % of patients, with low morbidity and mortality. PMID- 27191235 TI - Surgical outcomes of the endoscopic endonasal transsphenoidal approach for large and giant pituitary adenomas: institutional experience with special attention to approach-related complications. AB - Objective In this study, we investigate our institutional experience of patients who underwent endoscopic endonasal transsphenoidal approach for treatment of large and giant pituitary adenomas emphasizing the surgical results and approach related complications. Method The authors reviewed 28 consecutive patients who underwent surgery between March, 2010 and March, 2014. Results The mean preoperative tumor diameter was 4.6 cm. Gross-total resection was achieved in 14.3%, near-total in 10.7%, subtotal in 39.3%, and partial in 35.7%. Nine patients experienced improvement in visual acuity, while one patient worsened. The most common complications were transient diabetes insipidus (53%), new pituitary deficit (35.7%), endonasal adhesions (21.4%), and cerebrospinal fluid leak (17.8%). Surgical mortality was 7.1%. Conclusions Endoscopic endonasal transsphenoidal surgery is a valuable treatment option for large or giant pituitary adenomas, which results in high rates of surgical decompression of cerebrovascular structures. PMID- 27191236 TI - Pituitary macroadenoma: analysis of intercarotid artery distance compared to controls. AB - Objective To evaluate the intercarotid distance (ICD) of patients with pituitary macroadenoma and compare to heatlhy controls. Method We retrospectively reviewed contrast-enhanced MRI images from twenty consecutive patients diagnosed with non functioning pituitary macroadenoma, measured the ICD at two different levels (petrous segment - ICD1 and horizontal cavernous segment - ICD2) and compared to twenty paired controls. Results There was no statistically significant difference of the mean ICD1 between the groups and subgroups. For the ICD2 there was statistically significant difference between the case and controls. However, there was no significant difference between the patients with smaller adenomas and the controls. In contrast, the patients with giant adenomas showed statistically significantly higher ICD2 than the controls. Conclusion The ICD at the horizontal segment of the cavernous carotid tends to be wider in patients with giant pituitary adenomas than in healthy individuals or patients with smaller adenomas. PMID- 27191237 TI - 3-D simulation of posterior fossa reduction in Chiari I. AB - We proposed a 3D model to evaluate the role of platybasia and clivus length in the development of Chiari I (CI). Using a computer aided design software, two DICOM files of a normal CT scan and MR were used to simulate different clivus lengths (CL) and also different basal angles (BA). The final posterior fossa volume (PFV) was obtained for each variation and the percentage of the volumetric change was acquired with the same method. The initial normal values of CL and BA were 35.65 mm and 112.66o respectively, with a total PFV of 209 ml. Ranging the CL from 34.65 to 29.65 - 24.65 - 19.65, there was a PFV decrease of 0.47% - 1.12% - 1.69%, respectively. Ranging the BA from 122.66o to 127.66o - 142.66o, the PFV decreased 0.69% - 3.23%, respectively. Our model highlights the importance of the basal angle and clivus length to the development of CI. PMID- 27191238 TI - Predictors of quality of life after moderate to severe traumatic brain injury. AB - Objective To verify correlations between age, injury severity, length of stay (LOS), cognition, functional capacity and quality of life (QOL) six months after hospital discharge (HD) of victims of traumatic brain injury (TBI). Method 50 patients consecutively treated in a Brazilian emergency hospital were assessed at admission, HD and six months after HD. The assessment protocol consisted in Abbreviated Injury Scale, Injury Severity Score, Glasgow Coma Scale (GCS), Revised Trauma Score (RTS), Mini Mental Test, Barthel Index and World Health Organization QOL - Brief. Results Strong negative correlation was observed between LOS and GCS and LOS and RTS. An almost maximal correlation was found between RTS and GCS and functional capacity and GCS at HD. Age and LOS were considered independent predictors of QOL. Conclusion Age and LOS are independent predictors of QOL after moderate to severe TBI. PMID- 27191239 TI - Vestibular migraine: diagnosis challenges and need for targeted treatment. AB - Approximately 1% of the general population suffers from vestibular migraine. Despite the recently published diagnostic criteria, it is still underdiagnosed condition. The exact neural mechanisms of vestibular migraine are still unclear, but the variability of symptoms and clinical findings both during and between attacks suggests an important interaction between trigeminal and vestibular systems. Vestibular migraine often begins several years after typical migraine and has a variable clinical presentation. In vestibular migraine patients, the neurological and neurotological examination is mostly normal and the diagnosis will be based in the patient clinical history. Treatment trials that specialize on vestibular migraine are scarce and therapeutic recommendations are based on migraine guidelines. Controlled studies on the efficacy of pharmacologic interventions in the treatment of vestibular migraine should be performed. PMID- 27191240 TI - What's in a name? Problems, facts and controversies regarding neurological eponyms. AB - The use of eponyms in neurology remains controversial, and important questions have been raised about their appropriateness. Different approaches have been taken, with some eponyms being excluded, others replaced, and new ones being created. An example is Hallervorden-Spatz syndrome, which has been replaced by neurodegeneration with brain iron accuulatium (NBIA). Amiothoplic lateral sclerosys (ALS), for which the eponym is Charcot's disease, has been replaced in the USA by Lou Gehrig's disease. Guillain-Barre syndrome (GBS) is an eponym that is still the subject of controversy, and various different names are associated with it. Finally,restless legs syndrome (RLS), which was for years known as Ekbom's syndrome, has been rechristened as RLS/Willis-Ekbom syndrome. PMID- 27191241 TI - Hypertrophic olivary degeneration: unveiling the triangle of Guillain-Mollaret. PMID- 27191242 TI - Primary central nervous system lymphoma (PCNSL). PMID- 27191243 TI - Effects of aluminum oxide (Al2O3) nanoparticles on ECG, myocardial inflammatory cytokines, redox state, and connexin 43 and lipid profile in rats: possible cardioprotective effect of gallic acid. AB - The objectives of present study were to examine the effects of aluminum oxide (Al2O3) nanoparticles on myocardial functions, electrical activities, morphology, inflammation, redox state, and myocardial expression of connexin 43 (Cx43) and the effect of gallic acid (GA) on these effects in a rat animal model. Forty male albino rats were divided into 4 equal groups: the control (normal) group; the Al2O3 group, rats received Al2O3 (30 mg.kg(-1), i.p.) daily for 14 days; the nano alumina group, rats received nano-alumina (30 mg.kg(-1), i.p.) daily for 14 days; and the nano-alumina + GA group, rats received GA (100 mg.kg(-1) orally once daily) for 14 days before nano-alumina administration. The results showed disturbed ECG variables and significant increases in serum levels of LDH, creatine phosphokinase (CPK), CK-MB, triglycerides (TGs), cholesterol and LDL, nitric oxide (NO), and TNF-alpha and myocardial concentrations of NO, TNF-alpha, and malondialdehyde (MDA), with significant decreases in serum HDL and myocardial GSH, SOD, catalase (CAT), and Cx43 expression in the nano-alumina group. Pretreatment with GA improved significantly all parameters except serum and myocardial NO. We concluded that chronic administration of Al2O3 NPs caused myocardial dysfunctions, and pretreatment with GA ameliorates myocardial injury induced by nano-alumina, probably through its hypolipidaemic, anti-inflammatory, and antioxidant effects and upregulation of Cx43 in heart. PMID- 27191244 TI - Cell Adhesion and Proliferation on the "Living" Surface of a Polyelectrolyte Multilayer. AB - The adhesion of living eukaryotic cells to a substrate, one of the most complex problems in surface science, requires adsorption of extracellular proteins such as fibronectin. Thin films of polyelectrolyte complex made layer-by-layer (polyelectrolyte multilayers or PEMUs) offer a high degree of control of surface charge and composition-interconnected and essential variables for protein adhesion. Fibroblasts grown on multilayers of poly(styrenesulfonate), PSS, and poly(diallyldimethylammonium), PDADMA, with increasing thickness exhibit good adhesion until the 12th layer of polyelectrolyte has been added, whereupon there is a sudden transition to nonadhesive behavior. This sharp change is due to the migration of excess positive charge to the surface-a previously unrecognized property of PEMUs. Precise radiotracer assays of adsorbed (125)I-albumin show how protein adsorption is related to multilayer surface charge. With more negative surface charge density from the sulfonates of PSS, more albumin adsorbs to the surface. However, a loosely held or "soft corona" exchanges with serum protein under the Vroman effect, which is correlated with poor cell adhesion. A comprehensive view of cell adhesion highlights the central role of robust protein adhesion, which is required before any secondary effects of matrix stiffness on cell fate can come into play. PMID- 27191245 TI - Dielectrophoretic applications for disease diagnostics using lab-on-a-chip platforms. AB - Dielectrophoresis is a powerful technique used to distinguish distinct cellular identities in heterogeneous cell populations and to monitor changes in the cell state without the need for biochemical tags, including live and dead cells. Recent studies in the past decade have indicated that dielectrophoresis can be used to discriminate the disease state of cells by exploring the differences in the dielectric polarizabilities of the cells. Factors controlling the dielectric polarizability are dependent on the conductivity and permittivity of the cell and the suspending medium, the cell morphology, the internal structure, and the electric double layer effects associated with the charges on the cell surface. Diseased cells, such as those associated with malaria, cancer, dengue, anthrax and human African trypanosomiasis, could be spatially trapped by positive dielectrophoresis or spatially separated from other healthy cells by negative dielectrophoretic forces. The aim of this review was to provide a better and deeper understanding on how dielectrophoresis can be utilized to manipulate diseased cells. This review compiles and compares the significant findings obtained by researchers in manipulating abnormal or unhealthy cells. PMID- 27191246 TI - Visceral adiposity index and prognosis among patients with ischemic heart failure. AB - CONTEXT AND OBJECTIVES: The obesity paradox has already been established in relation to heart failure, but it is not known which obesity indicator best reflects this phenomenon. The aim of this study was to evaluate the association between obesity indexes and mortality among patients with heart failure. DESIGN AND SETTING: Cohort study conducted in the Department of Cardiology of Hospital Nossa Senhora da Conceicao (Brazil). METHODS: Clinical, demographic, socioeconomic, biochemical and anthropometric data on 116 patients aged 30 to 85 years with a diagnosis of heart failure were evaluated. Arm fat area, body mass index, body surface area, body adiposity index, lipid accumulation product (LAP) and visceral adiposity index (VAI) were calculated. Cox regression was used to perform survival analyses. RESULTS: At baseline, the individuals with ischemic heart failure who remained alive showed higher VAI (3.60 +/- 3.71 versus 1.48 +/- 1.58; P = 0.04) and a trend towards higher LAP, in comparison with the individuals who died. After an average follow-up of 14.3 months, ischemic heart failure patients who had VAI > 1.21 showed 78% lower risk of death (HR 0.12; 95% CI: 0.02-0.67; P = 0.02) and the Kaplan-Meier survival curves showed better prognosis for these individuals (P = 0.005; log-rank test). CONCLUSION: Our results suggest that VAI is a good predictor of better prognosis among ischemic heart failure patients. PMID- 27191247 TI - The effect of red grape seed extract on serum paraoxonase activity in patients with mild to moderate hyperlipidemia. AB - CONTEXT AND OBJECTIVE: Red grape seed extract (RGSE) contains oligomeric proanthocyanidin complexes as a class of flavonoids. These compounds are potent antioxidants and exert many health-promoting effects. This study aimed to determine the effects of RGSE on serum levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein AI (apo-AI) levels and paraoxonase (PON) activity in patients with mild to moderate hyperlipidemia (MMH). DESIGN AND SETTINGS: A randomized double-blind placebo-controlled clinical trial was conducted at Shahid-Modarres Hospital (Tehran, Iran) and Tabriz University of Medical Sciences. Seventy MMH patients were randomly assigned to receive treatment (200 mg/day of RGSE) or placebo for eight weeks. RESULTS: Significant elevation in serum levels of apo-AI (P = 0.001), HDL-C (P = 0.001) and PON activity (P = 0.001) and marked decreases in concentrations of TC (P = 0.015), TG (P = 0.011) and LDL-C (P = 0.014) were found in the cases. PON activity was significantly correlated with apo-AI (r = 0.270; P < 0.01) and HDL-C (r = 0.45; P < 0.001). Significant differences between the RGSE and control groups (before and after treatment) for TC (P = 0.001), TG (P = 0.001), PON (P = 0.03), apo-AI (P = 0.001) and LDL-C (P = 0.002) were seen. CONCLUSION: It is possible that RGSE increases PON activity mostly through increasing HDL-C and apo AI levels in MMH patients. It may thus have potential beneficial effects in preventing oxidative stress and atherosclerosis in these patients. PMID- 27191248 TI - Pneumonia caused by Bordetella bronchiseptica in two HIV-positive patients. AB - CONTEXT AND OBJECTIVE: Bordetella bronchiseptica (BB) is a Gram-negative coccobacillus responsible for respiratory diseases in dogs, cats and rabbits. Reports on its development in humans are rare. However, in immunosuppressed patients, especially in those with the immunodeficiency virus (HIV), BB can cause severe pulmonary infections. We report on two cases of pneumonia caused by BB in HIV-positive male patients in a university hospital. CASE REPORT: The first case comprised a 43-year-old patient who was admitted presenting chronic leg pain and coughing, with suspected pneumonia. BB was isolated from sputum culture and was successfully treated with trimethoprim/sulfamethoxazole in association with levofloxacin. The second case comprised a 49-year-old patient who was admitted presenting fever, nausea, sweating and a dry cough, also with suspected pneumonia. BB was isolated from sputum culture, tracheal secretions and bronchoalveolar lavage. The disease was treated with ciprofloxacin but the patient died. CONCLUSION: BB should be included in the etiology of pneumonia in immunodeficient HIV patients. As far as we know, these two were the first cases of pneumonia due to BB to occur in this university hospital. PMID- 27191249 TI - Factor structure and psychometric properties of the Connor-Davidson resilience scale among Brazilian adult patients. AB - CONTEXT AND OBJECTIVE: Personal resilience is associated with several mental health outcomes. The Connor-Davidson resilience scale (CD-RISC) is a widely used self-report measurement of resilience. This study aimed to investigate the reliability and validity of a Brazilian Portuguese version of the CD-RISC. DESIGN AND SETTING: Cross-sectional validation study carried out in the outpatient clinics of a public university hospital. METHODS: The cross-cultural adaptation followed established guidelines and involved interviews with 65 adults in psychiatric and non-psychiatric outpatient clinics at a teaching hospital. Validation was assessed through concurrent application of the Lipp Brazilian Stress Symptom Inventory (ISSL), Self-Report Questionnaire (SRQ), Sheehan Disability Scales (SDS) and Chronic Pain Grade (CPG) to 575 patients at the same setting. Temporal stability was verified through a second application to 123 participants. RESULTS: Factor analysis identified four factors, named tenacity, adaptability-tolerance, reliance on support from outside and intuition. The alpha coefficient of 0.93 and intraclass correlation coefficient of 0.84 indicated good internal consistency and temporal stability. Significant correlations between this version of the CD-RISC and the ISSL, SRQ, SDS and CPG were noted. The patients at the outpatient clinic for borderline personality had resilience scores that were significantly lower than those of the patients at the general anxiety or post-traumatic stress outpatient clinics. CONCLUSION: This Brazilian Portuguese version of the Connor-Davidson resilience scale exhibited adequate reliability and validity among a sample of Brazilian adult patients. PMID- 27191250 TI - Disability due to maternal common mental disorders (CMDs) as a risk factor for chronic childhood malnutrition: cross-sectional study. AB - CONTEXT AND OBJECTIVE: The disability associated with maternal common mental disorders (CMDs) is among the possible explanations for the association between chronic childhood malnutrition and CMDs. CMDs may impair the mother's ability to perform her role, particularly in deprived environments. The present study aimed to evaluate whether disability relating to CMDs could be part of the pathway of the association between childhood malnutrition and maternal CMDs. DESIGN AND SETTING: Cross-sectional study conducted in two institutions: one for malnourished children and another for eutrophic children living in a low-income community in the state of Alagoas, Brazil. METHOD: The cases consisted of 55 malnourished children aged from 12 to 60 months who were attending a nutritional rehabilitation center, with height-for-age z-scores < 2. The controls were 70 eutrophic children of the same age who were attending a day care center in the same area as the cases. The Self-Report Questionnaire made it possible to identify likely cases of maternal CMD. The Sheehan Disability Scale enabled evaluation of the associated disability. RESULTS: Chronic childhood malnutrition was significantly associated with maternal disability relating to CMDs (OR = 2.28; 95% CI: 1.02-5.1). The best logistic regression model using chronic childhood malnutrition as the dependent variable included the following independent variables: higher number of people living in the household; absence of the biological father from the household; and maternal disability relating to CMDs. CONCLUSIONS: If confirmed, the association between chronic childhood malnutrition and maternal disability relating to CMDs may be useful in helping to identify the causal chain between childhood malnutrition and maternal CMDs and to indicate environmental risk factors associated with chronic childhood malnutrition. PMID- 27191251 TI - Are normal-weight adolescents satisfied with their weight? AB - CONTEXT AND OBJECTIVE: The high prevalence of obesity has led to public policies for combating it. People with normal weight may gain greater awareness of this issue and change their perceptions of their weight. The aim of this study was to evaluate the prevalence of body weight dissatisfaction among normal-weight adolescents, according to demographic and socioeconomic variables, health-related behavior and morbidities. DESIGN AND SETTING: Population-based cross-sectional study that used data from a health survey conducted in the city of Campinas, Sao Paulo, in 2008-2009. METHODS: The prevalence and prevalence ratios of weight dissatisfaction were estimated according to independent variables, by means of simple and multiple Poisson regression. RESULTS: 573 normal-weight adolescents aged 10 to 19 years (mean age 14.7 years) were analyzed. The prevalence of weight dissatisfaction was 43.7% (95% confidence interval, CI: 37.8-49.8). Higher prevalences of weight dissatisfaction were observed among females, individuals aged 15 to 19 years, those whose households had eight or more domestic appliances, former smokers, individuals who reported alcohol intake and those who had one or more chronic diseases. Lower prevalence of dissatisfaction was observed among adolescents living in substandard housing. Among the normal-weight adolescents, 26.1% wished to lose weight and 17.6% wished to gain weight. CONCLUSION: The results from this study indicate that even when weight is seen to be within the normal range, a high proportion of adolescents express dissatisfaction with their weight, especially females, older adolescents and those of higher socioeconomic level. PMID- 27191252 TI - Conjugation Strategy Strongly Impacts the Conformational Stability of a PEG Protein Conjugate. AB - Site-specific PEGylation is an important strategy for enhancing the pharmacokinetic properties of protein drugs, and has been enabled by the recent development of many chemoselective reactions for protein side-chain modification. However, the impact of these different conjugation strategies on the properties of PEG-protein conjugates is poorly understood. Here we show that the ability of PEG to enhance protein conformational stability depends strongly on the identity of the PEG-protein linker, with the most stabilizing linkers involving conjugation of PEG to planar polar groups near the peptide backbone. We also find that branched PEGs provide superior stabilization relative to their linear counterparts, suggesting additional applications for branched PEGs in protein stabilization. PMID- 27191254 TI - A scoping review to understand "leadership" in interprofessional education and practice. AB - This scoping study examined how "leadership" is referred to and used in interprofessional education and practice. A total of 114 refereed articles were reviewed to determine how leadership is defined, conceptualised, and theorised. The review also examined what capabilities were identified for effective interprofessional leadership. The majority of papers were empirical studies undertaken by researchers based in North America. The majority of articles did not refer to a specific leadership approach, nor did they define, describe, or theorise leadership. Moreover, "leadership" capabilities were rarely identified. Articles generally focused on health practitioners and educators or students as leaders with little exploration of leadership at higher levels (e.g. executive, accrediting bodies, government). This review indicates the need for a more critical examination of interprofessional leadership and the capabilities required to lead the changes required in both education and practice settings. The goal of this article is to stimulate discussion and more sophisticated, shared understandings of interprofessional leadership for the professions. Recommendations for future research are required in both education and practice settings. PMID- 27191255 TI - Changes in human pulp blood flow during canine retraction. AB - AIM: To evaluate the effects of maxillary canine retraction on pulpal blood flow (PBF) in humans as recorded by laser Doppler flowmetry (LDF). METHODS: Maxillary canines of 24 participants were divided into two groups (n = 12 each). Teeth in the study group underwent maxillary canine retraction using mini-implants as anchorage for approximately 4 months, with 100 g of force applied via coil springs. Subjects in the control group received no orthodontic treatment. LDF measurements were recorded at baseline (T0); during retraction, at 24 hours (T1), 3 days (T2), 7 days (T3) and 1 month (T4); and at the end of retraction (T5) in the study group and at similar time-points in control subjects. Data were analyzed using the Friedman, Wilcoxon signed rank and Mann-Whitney U tests, with the significance level set at 0.05. RESULTS: No significant changes in PBF perfusion units (PU) were observed in the control group over the course of the study. However, PBF in the study group increased significantly from T0 (3.6 +/- 0.2 PU) to T1 (3.7 +/- 0.2 PU, p < 0.001) and decreased severely from T1 to T2 (3.3 +/- 0.1, p < 0.001). PBF in the study group was still significantly lower at T3 (3.4 +/- 0.1 PU, p < 0.001) in comparison to T0; however, at T4 and T5, PBF was found to have returned to pre-retraction levels. CONCLUSION: The fact that PBF values returned to initial levels within one month of the initiation of retraction despite short-term, hyperaemic, regressive changes demonstrates that the changes observed in PBF during canine retraction are reversible. PMID- 27191253 TI - Pregnancy, Labor, and Delivery after Ebola Virus Disease and Implications for Infection Control in Obstetric Services, United States. AB - Many of the survivors of the 2014-2015 epidemic of Ebola virus disease (EVD) in western Africa were women of childbearing age. Limited clinical and laboratory data exist that describe these women's pregnancies and outcomes. We report the case of an EVD survivor who became pregnant and delivered her child in the United States, and we discuss implications of this case for infection control practices in obstetric services. Hospitals in the United States must be prepared to care for EVD survivors. PMID- 27191256 TI - Abdominal scar characteristics as a predictor of cervical stenosis after abdominal radical trachelectomy. AB - To investigate whether abdominal scar characteristics could predict the occurrence of cervical stenosis after abdominal radical trachelectomy (ART), we conducted a retrospective study and investigated the relationship between abdominal scar characteristics and the occurrence of cervical stenosis in patients one year after undergoing ART. The abdominal scars were evaluated using the Vancouver Scar Scale (VSS). Seventy-two participants were enrolled in the study, including 15 (20.8%) women with cervical stenosis, and 57 (79.2%) without stenosis. Results showed that the mean abdominal scar score assessed by VSS was higher in patients with cervical stenosis (7, range: 1-10) compared to those without stenosis (4, range: 0-9) (P = 0.001). Incidence rates of cervical stenosis increased with the VSS score. For women with VSS scores of 0 to 4, 5, 6, 7, 8, 9 and 10, respectively, the occurrences of cervical stenosis were 6.1%, 16.7%, 16.7%, 27.3%, 37.5%, 50% and 100%. The cutoff point of VSS score was 7 according to the receiver operating characteristic (ROC) curve. Fourteen of the 15 stenosis happened either in patients without anti-stenosis tools (Foley catheters or tailed intrauterine devices) placed during the surgery or after the devices were removed. Our results demonstrated that VSS is an effective approach to assess the presence of cervical stenosis after ART. Women who have an abdominal scar with a VSS score > 7 have a high risk of developing isthmic stenosis without anti-stenosis tools in place. PMID- 27191257 TI - Demonstration of a WNT5A-IL-6 positive feedback loop in melanoma cells: Dual interference of this loop more effectively impairs melanoma cell invasion. AB - Increased expression and signalling of WNT5A and interleukin-6 (IL-6) have both been shown to promote melanoma progression. Here, we investigated the proposed existence of a WNT5A-IL-6 positive feedback loop that drives melanoma migration and invasion. First, the HOPP algorithm revealed that the invasive phenotype of cultured melanoma cells was significantly correlated with increased expression of WNT5A or IL-6. In three invasive melanoma cell lines, endogenous WNT5A protein expression was related to IL-6 protein secretion. Knockdown with anti-IL-6 siRNAs or treating WM852 melanoma cells with a neutralising anti-IL-6 antibody reduced WNT5A protein expression. Conversely, the silencing of WNT5A expression by WNT5A siRNAs or treating WM852 melanoma cells with Box5 (a WNT5A antagonist) significantly reduced IL-6 secretion. Interestingly, these effects occurred at the protein level but not at the transcriptional levels. Functionally, we demonstrated that combined siRNA knockdown of WNT5A and IL-6 expression or the simultaneous inhibition of WNT5A and IL-6 signalling inhibited melanoma cell invasion more effectively than suppressing each factor individually. Together, our results demonstrate that WNT5A and IL-6 are connected through a positive feedback loop in melanoma cells and that the combined targeting of both molecules could serve as an effective therapeutic means to reduce melanoma metastasis. PMID- 27191258 TI - Rs2853677 modulates Snail1 binding to the TERT enhancer and affects lung adenocarcinoma susceptibility. AB - Genome wide association studies (GWAS) have shown that SNPs in non-coding regions are associated with inherited susceptibility to cancer. The effect of one single SNP, however, is weak. To identify potential co-factors of SNPs, we investigated the underlying mechanism by which SNPs affect lung cancer susceptibility. We found that rs2853677 is located within the Snail1 binding site in a TERT enhancer. This enhancer increases TERT transcription when juxtaposed to the TERT promoter. The binding of Snail1 to the enhancer disrupts enhancer-promoter colocalization and silences TERT transcription. The high risk variant of rs2853677 disrupts the Snail1 binding site and derepresses TERT expression in response to Snail1 upregulation, thus increasing lung adenocarcinoma susceptibility. Our data suggest that Snail1 may be a co-factor of rs2853677 for predicting lung adenocarcinoma susceptibility and prognosis. PMID- 27191260 TI - HEY2, a target of miR-137, indicates poor outcomes and promotes cell proliferation and migration in hepatocellular carcinoma. AB - HEY2, a bHLH transcription factor, has been implicated in the progression of human cancers. Here, we showed that HEY2 expression was markedly increased in HCC, compared with the adjacent nontumorous tissues. High HEY2 expression was closely correlated with tumor multiplicity, tumor differentiation and TNM stage. Kaplan-Meier analyses revealed that HEY2 expression was significantly associated with poor overall and disease-free survival in a training cohort of 361 patients with HCC. The prognostic implication of HEY2 was validated in another cohort of 169 HCC patients. Multivariate Cox regression model indicated HEY2 as an independent factor for overall survival in HCC (Hazard ratio = 1.645, 95% confident interval: 1.309-2.067, P<0.001). We also demonstrated that HEY2 expression was inhibited by miR-137. In clinical samples, HEY2 expression was reversely associated to miR-137 expression. Furthermore, overexpression of HEY2 increased cell viabilities, colony formation and cell migration, whereas knockdown of HEY2 resulted in the opposite phenotypes. Collectively, our data suggest HEY2 as a promising biomarker for unfavorable outcomes and a novel therapeutic target for the clinical management of HCC. PMID- 27191259 TI - Notch1 pathway-mediated microRNA-151-5p promotes gastric cancer progression. AB - Gastric carcinoma is the third leading cause of lethal cancer worldwide. Previous studies showed that Notch1 receptor intracellular domain (N1IC), the activated form of Notch1 receptor, promotes gastric cancer progression. It has been demonstrated that a significant cross-talk interplays between Notch pathways and microRNAs (miRNAs) in controlling tumorigenesis. This study identified an intronic microRNA-151 (miR-151), which consists of two mature miRNAs, miR-151-3p and miR-151-5p, as a Notch1 receptor-induced miRNA in gastric cancer cells. Activation of Notch1 pathway enhanced expressions of miR-151 and its host gene, focal adhesion kinase (FAK), in gastric cancer cells. The levels of miR-151 in gastric cancer samples were higher than those of adjacent non-tumor samples. Activated Notch1 pathway induced CBF1-dependent FAK promoter activity. The ectopic expression of miR-151 promoted growth and progression of SC-M1 gastric cancer cells including cell viability and colony formation, migration, and invasion abilities. Activated Notch1 pathway could augment progression of gastric cancer cells through miR-151-5p and FAK. The mRNA levels of pluripotency genes, Nanog and SOX-2, tumorsphere formation ability, tumor growth, and lung metastasis of SC-M1 cells were elevated by activated Notch1 pathway through miR-151-5p. Furthermore, miR-151-5p could target 3'-untranslated region (3'-UTR) of p53 mRNA and down-regulate p53 level in SC-M1 cells. Mechanistically, Notch1/miR-151-5p axis contributed to progression of SC-M1 cells through down-regulation of p53 which in turn repressed FAK promoter activity. Taken together, these results suggest that Notch1 pathway and miR-151-5p interplay with p53 in a reciprocal regulation loop in controlling gastric carcinogenesis. PMID- 27191262 TI - Long non-coding RNA Malat1 promotes gallbladder cancer development by acting as a molecular sponge to regulate miR-206. AB - Long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (Malat1) functions as an oncogene in many types of human cancer. In this study, we show that Malat1 is overexpressed in gallbladder cancer (GBC) tissue and cells. The high Malat1 levels correlated positively with tumor size and lymphatic metastasis, and correlated negatively with overall survival. We also show that Malat1 functions as a competing endogenous RNA (ceRNA) for miR-206. Because miR 206 directly suppresses expression of ANXA2 and KRAS, which are thought to promote GBC progression, Malat1 binding of miR-206 in GBC tissue and cells has an oncogenic effect. Conversely, Malat1 knockdown inhibits proliferation and invasion by GBC cells while increasing apoptosis. In vivo, silencing Malat1 decreases tumor volume. These results suggest Malat1 could potentially serve as a therapeutic target and prognostic marker for GBC. PMID- 27191261 TI - A novel p70 S6 kinase-microRNA biogenesis axis mediates multicellular spheroid formation in ovarian cancer progression. AB - Ovarian cancer is the leading cause of death of all gynecologic tumors, associated with widespread peritoneal dissemination and malignant ascites. Key to this is the ability to form multicellular spheroids (MCS); however, the tumor specific factors that regulate MCS formation are unclear. p70 S6 kinase (p70S6K), which is a downstream effector of phosphatidylinositol 3-kinase/Akt, is frequently constitutively active in ovarian carcinoma. Here we identify p70S6K as a vital regulator of MCS formation. We also uncover a new mechanism of p70S6K function as a component of the microRNA biogenesis machinery in this process. We show that p70S6K phosphorylates, and inhibits the interaction of tristetraprolin (TTP) and Dicer that promotes the expression of a subset of miRNAs, including the maturation of miR-145. Twist and Sox9 are two divergent targets of miR-145, thereby enhancing N-cadherin, but not other cadherin, expression and MCS formation. Activating miR-145 suppresses ovarian tumor growth and metastasis in an orthotopic xenograft mouse model. Meta-analysis in the Oncomine database reveals that high p70S6K and low TTP levels are associated with ovarian tumor progression. These results define a critical link between p70S6K, miRNA maturation, and MCS formation that may underlie poor clinical outcome of ovarian cancer patients for developing novel therapeutic strategies. PMID- 27191263 TI - Derivatives of 6-cinnamamido-quinoline-4-carboxamide impair lysosome function and induce apoptosis. AB - Autophagy is a lysosomal degradative process that protects cancer cells from multiple types of stress. In this study, we synthesized a series of derivatives of 6-cinnamamido-quinoline-4-carboxamide (CiQ), and investigated their effects on the proliferation and autophagy of cancer cells in vitro. These derivatives effectively inhibited the proliferation of a broad spectrum of cancer cell lines. Further study revealed that CiQ derivatives may induce autophagy and result in disruption of autophagy propagation. Consequently, these derivatives triggered massive apoptosis, as evidenced by caspase-9 activation and PARP cleavage. Blockage of autophagy by depletion of autophagy related gene ATG5 or BECN1 considerably alleviated CiQ-induced cell death, indicating that autophagy may mediate CiQ-induced cell death. Furthermore, treatment with CiQ derivatives increased lysosome membrane permeability (LMP) and enhanced accumulation of ubiquitinated proteins, which collectively indicate impaired lysosome function. In addition, treatment of cells with CiQ derivatives activated extracellular signal-regulated kinase (ERK); abrogation of ERK activation, either by treating cells with U0126, an inhibitor of mitogen-activated protein/ERK kinase 1 (MEK1), or by ectopically overexpressing a dominant-negative MEK1, significantly reduced CiQ derivative-induced LMP, LC3 and p62 accumulation, and cytotoxicity. These results indicate that CiQ derivatives activate ERK and disrupt lysosome function, thereby altering autophagic flux and resulting in apoptotic cell death. PMID- 27191264 TI - Simm530, a novel and highly selective c-Met inhibitor, blocks c-Met-stimulated signaling and neoplastic activities. AB - The aberrant c-Met activation has been implicated in a variety of human cancers for its critical role in tumor growth, metastasis and tumor angiogenesis. Thus, c Met axis presents as an attractive therapeutic target. Notably, most of these c Met inhibitors currently being evaluated in clinical trials lack selectivity and target multiple kinases, often accounting for the undesirable toxicities. Here we described Simm530 as a potent and selective c-Met inhibitor. Simm530 demonstrated >2,000 fold selectivity for c-Met compared with other 282 kinases, making it one of the most selective c-Met inhibitors described to date. This inhibitor significantly blocked c-Met signaling pathways regardless of mechanistic complexity implicated in c-Met activation. As a result, Simm530 led to substantial inhibition of c-Met-promoted cell proliferation, migration, invasion, ECM degradation, cell scattering and invasive growth. In addition, Simm530 inhibited primary human umbilical vascular endothelial cell (HUVEC) proliferation, decreased intratumoral CD31 expression and plasma pro-angiogenic factor interleukin-8 secretion, suggesting its significant anti-angiogenic properties. Simm530 resulted in dose-dependent inhibition of c-Met phosphorylation and tumor growth in c-Met-driven lung and gastric cancer xenografts. And, the inhibitor is well tolerated even at doses that achieve complete tumor regression. Together, Simm530 is a potent and highly selective c Met kinase inhibitor that may have promising therapeutic potential in c-Met driven cancer treatment. PMID- 27191265 TI - Long noncoding RNA DANCR promotes invasion of prostate cancer through epigenetically silencing expression of TIMP2/3. AB - LncRNA DANCR suppresses differentiation of epithelial cells, however, its function in prostate cancer development is still unknown. In the present study, we found the expression of DANCR increases in prostate cancer tissues and cells compared to normal prostate tissues and cells, moreover, DANCR promotes invasion and migration of prostate cancer cells in vitro and metastasis of tumor xenografts in nude mice. Mechanistically, we found that TIMP2/3, which are critical metastasis inhibitor of prostate cancer, were down-regulated by DANCR synergistically with EZH2 through epigenetically silencing their promoter by chromatin immunoprecipitation assay. In addition, we further investigated whether DANCR is regulated by the differentiation-promoting androgen-androgen receptor (AR) pathway and found that DANCR expression is repressed by androgen-AR; furthermore, DANCR impedes the upregulation of TIMP2/3 and the suppression of invasion and migration by androgen-AR. On the other hand, interestingly, we found that in prostate cancer cells DANCR knockdown decreased the promotion of invasion and migration by the treatment of enzalutamide, which is an AR inhibitor. In summary, our results indicate that DANCR promotes prostate cancer invasion and metastasis through repressing the expression of TIMP2/3, and suggest that DANCR could be a potential target for preventing prostate cancer metastasis, and knockdown DANCR may lessen the potential side effect of AR inhibitor. PMID- 27191266 TI - DNA demethylating agent decitabine broadens the peripheral T cell receptor repertoire. AB - PURPOSE: Decitabine, a promising epi-immunotherapeutic agent has shown clinical responses in solid tumor patients, while the anti-tumor mechanisms were unclear. We aimed to investigate the immunomodulatory effect of decitabine in peripheral T cells. EXPERIMENTAL DESIGN: We applied next-generation sequencing to investigate the complementarity-determining region 3 (CDR3) of the TCRbeta gene, the diversity of which acts as the prerequisite for the host immune system to recognize the universal foreign antigens. We collected the peripheral blood mononuclear cells (PBMCs) from 4 patients, at baseline and after 2 cycles of low dose decitabine therapy. RESULTS: An increase of the unique productive sequences of the CDR3 of TCRbeta was observed in all of the 4 patients after decitabine treatment, which was characterized by a lower abundance of expanded clones and increased TCR diversity compared with before decitabine treatment. Further analysis showed a tendency for CD4 T cells with an increased CD4/CD8 ratio in response to decitabine therapy. In addition, the genome-wide expression alterations confirmed the effects of decitabine on immune reconstitution, and the increase of TCR excision circles (TRECs) was validated. CONCLUSIONS: The low-dose DNMT inhibitor decitabine broadens the peripheral T cell repertoire, providing a novel role for the epigenetic modifying agent in anti-tumor immune enhancement. PMID- 27191268 TI - Quantitative assessment of the association between APC promoter methylation and breast cancer. AB - Adenomatous polyposis coli (APC) is an important tumor suppressor gene in breast cancer. However, there were inconsistent conclusions in the association between APC promoter methylation and breast cancer. Hence, we conducted a meta-analysis to quantitatively assess the clinicopathological significance and diagnosis role of APC methylation in breast cancer. In total, 3172 samples from 29 studies were performed in this study. The odds ratio (OR) of APC methylation was 5.92 (95% CI = 3.16-11.07) in breast cancer cases compared to controls,. The APC promoter methylation was associated with cancer stage (OR = 0.47, 95% CI = 0.28-0.80, P = 0.006), lymph node metastases (OR = 0.55, 95% CI = 0.36-0.84, P = 0.005) and ER status (OR = 1.34, 95% CI = 1.03-1.73, P = 0.003) in breast cancer. Furthermore, the sensitivity and specificity for all included studies were 0.444 (95% CI: 0.321-0.575, P < 0.0001) and 0.976 (95% CI: 0.916-0.993, P < 0.0001), respectively. These results suggested that APC promoter methylation was associated with breast cancer risk, and it could be a valuable biomarker for diagnosis, treatment and prognosis of breast cancer. PMID- 27191267 TI - Identification of polycystic ovary syndrome potential drug targets based on pathobiological similarity in the protein-protein interaction network. AB - Polycystic ovary syndrome (PCOS) is one of the most common endocrinological disorders in reproductive aged women. PCOS and Type 2 Diabetes (T2D) are closely linked in multiple levels and possess high pathobiological similarity. Here, we put forward a new computational approach based on the pathobiological similarity to identify PCOS potential drug target modules (PPDT-Modules) and PCOS potential drug targets in the protein-protein interaction network (PPIN). From the systems level and biological background, 1 PPDT-Module and 22 PCOS potential drug targets were identified, 21 of which were verified by literatures to be associated with the pathogenesis of PCOS. 42 drugs targeting to 13 PCOS potential drug targets were investigated experimentally or clinically for PCOS. Evaluated by independent datasets, the whole PPDT-Module and 22 PCOS potential drug targets could not only reveal the drug response, but also distinguish the statuses between normal and disease. Our identified PPDT-Module and PCOS potential drug targets would shed light on the treatment of PCOS. And our approach would provide valuable insights to research on the pathogenesis and drug response of other diseases. PMID- 27191269 TI - Targeting glioma stem cells enhances anti-tumor effect of boron neutron capture therapy. AB - The uptake of (10)boron by tumor cells plays an important role for cell damage in boron neutron capture therapy (BNCT). CD133 is frequently expressed in the membrane of glioma stem cells (GSCs), resistant to radiotherapy and chemotherapy, and represents a potential therapeutic target. To increase (10)boron uptake in GSCs, we created a polyamido amine dendrimer, conjugated CD133 monoclonal antibodies, encapsulating mercaptoundecahydrododecaborate (BSH) in void spaces, and monitored the uptake of the bioconjugate nanoparticles by GSCs in vitro and in vivo. Fluorescence microscopy showed the specific uptake of the bioconjugate nanoparticles by CD133-positive GSCs. Treatment with the biconjugate nanoparticles resulted in a significant lethal effect after neutron radiation due to efficient and CD133-independent cellular targeting and uptake in CD133 expressing GSCs. A significantly longer survival occurred in combination with the biconjugate nanoparticles and BSH compared with BSH alone in human intracranial GBM models employing CD133-positive GSCs xenografts. Our data demonstrated that this bioconjugate nanoparticle targets human CD133-positive GSCs and is a potential boron agent in BNCT. PMID- 27191270 TI - MiR-23a-depressed autophagy is a participant in PUVA- and UVB-induced premature senescence. AB - Autophagy is a cellular catabolic mechanism that is activated in response to stress conditions, including ultraviolet (UV) irradiation, starvation, and misfolded protein accumulation. Abnormalities in autophagy are associated with several pathologies, including aging and cancer. Furthermore, recent studies have demonstrated that microRNAs (miRNAs) are potent modulators of the autophagy pathway. As a result, the current study aims to elucidate the role of the autophagy-related miRNA miR-23ain the process of photoaging. Experiments demonstrated that the antagomir-mediated inactivation of miR-23a resulted in the stimulation of PUVA- and UVB-depressed autophagy flux and protected human fibroblasts from premature senescence. Furthermore, AMBRA1 was identified as a miR-23a target. AMBRA1 cellular levels increased following the introduction of miR-23a antagomirs. And a bioinformatics analysis revealed that the AMBRA1 3' UTR contains functional miR-23a responsive sequences. Finally, it was also demonstrated that both AMBRA1 overexpression and Rapamycin treatment were both able to rescue fibroblasts from PUVA and UVB irradiation-induced autophagy inhibition, but that these effects could also be mitigated by miR-23a overexpression. Therefore, this study concludes that miR-23a-regulated autophagy is a novel and important regulator of ultraviolet-induced premature senescence and AMBRA1 is a rate-limiting miRNA target in this pathway. PMID- 27191273 TI - Chance to change how NMC spends your subs. AB - It will happen to every nurse and midwife each year, and they can barely fail to notice: L120 leaves his or her bank account and is deposited in the coffers of the Nursing and Midwifery Council. PMID- 27191271 TI - NPR-C gene polymorphism is associated with increased susceptibility to coronary artery disease in Chinese Han population: a multicenter study. AB - To find a new locus that confers significant susceptibility to CAD in Chinese Han population, a genome-wide association study in 200 "extreme individuals" from a Shandong cohort and a pathway-based candidate gene study from a Shanghai cohort (293 CAD/293 controls) were simultaneously performed. Amongst them, 13 SNPs associated with CAD were selected to conduct validation and replication studies in additional 3363 CAD patients and 3148 controls. A novel locus rs700926 in natriuretic peptide receptor C (NPR-C) was identified in Shandong and Hubei cohorts. Then rs700926 and other nine tag SNPs were genotyped in four geographically different populations (Shandong, Shaanxi, Hubei and Sichuan cohorts), and 6 SNPs (rs700926, rs1833529, rs2270915, rs17541471, rs3792758 and rs696831) showed stronger association with CAD, regardless of single or combined analysis. We further genotyped rs2270915 and 10 additional tag SNPs in a central China cohort and identified rs12697273 and rs10066436 as the loci associated with CAD. All these positive associations remained significant after adjustment for traditional risk factors of CAD. NPR-C gene SNPs significantly contribute to CAD susceptibility in the Chinese Han population. PMID- 27191274 TI - Overstretched staff have little time to comfort patients, survey reveals. AB - Almost three quarters of nurses feel they do not have enough time to comfort or talk to patients, Unison's annual safe staffing survey has shown. PMID- 27191276 TI - General practice plan aims to boost nurse numbers. AB - A multi-billion pound investment to counter pressures facing general practice in England includes at least L15 million to develop practice nursing. PMID- 27191275 TI - Queen's Nursing Institute backs #1hour2empower campaign. AB - The Queen's Nursing Institute is the latest organisation to give its backing to RCNi's #1hour2empower campaign. PMID- 27191277 TI - DH reveals vision for 'modernising' NMC framework. AB - A consultation on modernising the Nursing and Midwifery Council's legal framework has been launched by the Department of Health. PMID- 27191272 TI - The tumor suppressive miR-200b subfamily is an ERG target gene in human prostate tumors. AB - The TMPRSS2-ERG fusion occurs in approximately 50% of prostate cancer (PCa), resulting in expression of the oncogenic ERG in the prostate. Because ERG is a transcriptional activator, we hypothesized that ERG-regulated genes contribute to PCa development. Since microRNA (miRNA) has crucial functions in cancer, we searched for miRNAs regulated by ERG in PCas. We mined published datasets based on the MSKCC Prostate Oncogene Project, in which a comprehensive analysis defined the miRNA transcriptomes in 113 PCas. We retrieved the miRNA expression datasets, and identified miRNAs differentially expressed between ERG-positive and ERG negative samples. Out of 369 miRNAs, miR-200a, -200b, -429 and -205 are the only miRNAs significantly increased in ERG-positive tumors. Strikingly, miR-200a, 200b and -429 are transcribed as a single polycistronic transcript, suggesting they are regulated at the transcriptional level. With ChIP-qPCR and in vitro binding assay, we identified two functional ETS motifs in the miR-200b/a/429 gene promoter. Knockdown of ERG in PCa cells reduced expression of these three miRNAs. In agreement with the well-established tumor suppressor function, overexpression of the miR-200b/a/429 gene inhibited PCa cell growth and invasion. In summary, our study reveals that miR-200b/a/429 is an ERG target gene, which implicates an important role in TMPRSS2/ERG-dependent PCa development. Although induction of the tumor suppressive miR-200b subfamily by oncogenic ERG appears to be counterintuitive, it is consistent with the observation that the vast majority of primary prostate cancers are slow-growing and indolent. PMID- 27191278 TI - Ministers defer legal move to curtail time staff can spend on union duties. AB - The RCN has welcomed the delay in the introduction of a cap on time staff representatives can spend on union duties. PMID- 27191279 TI - Photographers capture the rich landscape of nursing in 2016. AB - The RCN is inviting members of the public to choose the photograph they think defines nursing in the 21st century. PMID- 27191280 TI - Trust asks NMC to change language threshold for overseas recruits. AB - An NHS trust has written to the Nursing and Midwifery Council asking the regulator to lower its English language test pass mark so it can recruit more nurses from overseas. PMID- 27191281 TI - Staffing among biggest hurdles in meeting new mental health targets. AB - Ensuring there are enough staff working in mental health care will be one of the biggest challenges in improving patient access to services. PMID- 27191282 TI - 'It is now time for the next generation of improvement'. AB - Mental health nurse Claire Murdoch, pictured, has been appointed NHS England's new national mental health director. PMID- 27191283 TI - Growing demands on end of life care. AB - Extra funding for end of life community care is needed to help the NHS and social services cope with growing numbers of people dying from cancer, a charity has warned. PMID- 27191285 TI - RCN calls for improved information sharing on FGM. AB - Updated guidance on dealing with and reporting cases of female genital mutilation (FGM) emphasises the need to improve information sharing across health and social care services. PMID- 27191286 TI - Should we stay or should we go? Referendum reflections for nurses. AB - With the EU referendum looming, nurses will be weighing up what a vote to stay in, or to leave, the European Union would mean for their jobs and healthcare in the UK. PMID- 27191287 TI - Cancer patients treated at home live longer than those receiving care in hospital. AB - Patients with cancer who die at home live longer than those who die in hospital, new study results suggest. PMID- 27191289 TI - Overfed toddlers heading for obesity with current diet. AB - UK toddlers are consuming more than the recommended amount of calories and protein, potentially putting them at risk of obesity in later life, say University College London researchers. PMID- 27191288 TI - Liver transplant patients face further complications if they have high body mass index. AB - Patients with a high body mass index (BMI) who have a liver transplant face an increased risk of developing steatosis - when the liver becomes infiltrated with fat - say researchers. PMID- 27191291 TI - Use of cannabis in pregnancy could lead to health problems in newborn babies. AB - Use of cannabis in pregnancy is linked to low birthweight and the need for intensive care, say US researchers. PMID- 27191290 TI - Primary care services do not need to be sited in emergency departments. AB - There is little evidence to back locating primary care services in emergency/urgent care facilities, a new study suggests. PMID- 27191293 TI - First steps towards a brighter future. PMID- 27191292 TI - Scarlet fever. AB - Essential facts Scarlet fever is characterised by a rash that usually accompanies a sore throat and flushed cheeks. It is mainly a childhood illness. While this contagious disease rarely poses a danger to life today, outbreaks in the past led to many deaths. PMID- 27191294 TI - Help in raising concerns about child abuse. PMID- 27191296 TI - Every contact counts. AB - Almost two in three adults are overweight or obese, which puts the majority of us at a significantly high risk of life threatening illnesses like type 2 diabetes, heart disease and certain cancers. PMID- 27191295 TI - Great achievements by dedicated nurses. AB - Like many nurses, those featured here are motivated by a desire to do everything they can to give high quality care to their patients. Nurses are often reluctant to seek recognition for their achievements, but by talking publicly about the difference they have made, Gillian Elwood, Anja Templin and Sandra Wood are helping to share good practice. PMID- 27191297 TI - Clarity of vision. AB - It is rather like painting the Forth Road Bridge, running to stand still, or akin to King Canute trying to turn back the waters. PMID- 27191298 TI - Voices - Funding of student places is a topic on everyone's mind, says Crystal Oldman. AB - Last week nurses from across the country gathered in London for the Queen's Nurses annual meeting. PMID- 27191300 TI - Readers panel - Facing up to climate change. AB - Our experts consider a hot topic of the day. PMID- 27191299 TI - Listen again. AB - At last I've caught up. Not only does my new-to-me but previously-loved motor have climate control and a heated windscreen, it lets me play music from my phone. PMID- 27191301 TI - Workplace wisdom. AB - What advice would you give to nurses who wish to work flexible hours to fit in with caring responsibilities? PMID- 27191306 TI - The best of the week's health-related TV and radio. AB - Our roundup of what's on. PMID- 27191302 TI - Starting out - I was moved by family's kindness and generosity in the face of tragedy. AB - The moment that inspired me to train as a nurse was an emotional one. I worked as a healthcare assistant before beginning training as a nurse. Several years ago I came across a patient who will always stick in my memory... even though we never spoke. PMID- 27191307 TI - Hearing Check app. AB - This free app from the charity Action on Hearing Loss is a quick way to check users' hearing. Each section provides well laid-out information with links to further content. PMID- 27191308 TI - Consultation's sleight of hand seeks to sugar unpalatable bursaries pill. AB - The Department of Health's consultation on student bursaries has begun and people are being encouraged to take part in it. However, this consultation is not a consultation - it is predictable spin where sleight of hand seeks to sugar an unpalatable pill. PMID- 27191309 TI - The right way and the wrong way of getting out of a chair. AB - Many thanks for publishing our article 'An integrated practice approach to mobility care for older people' (CPD, March 16). It looked great, however I have one comment. The picture on the Contents page to help locate the article in the magazine is misleading. It illustrates a common mistake when assisting people with mobility; encouraging or letting them put their hands on their walker when they attempt to stand. PMID- 27191310 TI - Age discrimination by fellow nurses is forcing me to leave. AB - I would like to share my upsetting experience of working in an acute hospital. I am an older, experienced nurse with a wide range of knowledge within different specialties. Due to a ward closure, I was transferred to another hospital to take charge of an acute receiving unit with a workforce of young, newly qualified nurses. Since then, I have been told to my face that I am too 'old' for the job and need to retire. Nurses seem to be sneering: 'Look at her, she is just an elderly nurse who is shockingly still working.' PMID- 27191313 TI - Golden opportunity on May 5 to send government a clear message. AB - It is worrying that there is little discussion about the upcoming local elections because this would be a golden opportunity to send the government a clear message. PMID- 27191314 TI - Education is needed to ensure high quality, fundamental care. AB - Nursing Standard (editorial April 13) refers to a comment about nursing associates by Health Education England's nurse director Lisa Bayliss-Pratt at a conference in Australia. She is quoted as saying that if we don't upskill our support workforce then graduate nurses may end up 'getting dragged down doing fundamental care'. PMID- 27191315 TI - Much needs to be done to forge alliances at grass roots. AB - Kevin Corbett and Jenny Finch (reflections, April 13) are right to call for stronger nursing alliances between primary care and community nurses. PMID- 27191316 TI - Raj Sookye: 1943-2016. AB - Retired ophthalmic theatre nurse Raj Sookye died in February aged 72, following a short illness. PMID- 27191317 TI - Stuart Frost: 1974-2016. AB - Mental health nurse Stuart Frost died in a road accident in the Worcestershire village of Shenstone on March 21. PMID- 27191318 TI - How to perform open tracheal suction via an endotracheal tube. AB - Rationale and key points Tracheal suction involves the removal of pulmonary secretions from the respiratory tract using negative pressure under sterile conditions. Practitioners should be aware of the indications for, and risks associated with, open tracheal suction via an endotracheal tube. ? Respiratory assessment of the patient should be carried out to identify when tracheal suction is required. ? A suction pressure of 80-120mmHg is recommended, and suction should last no longer than 15 seconds. ? Reassurance and support should be given to the patient to minimise any discomfort and distress that might result from tracheal suction. Reflective activity Clinical skills articles can help update your practice and ensure it remains evidence-based. Apply this article to your practice. Reflect on and write a short account of: 1. How you think this article will change your practice when performing open tracheal suction via an endotracheal tube. 2. How you could use this resource to educate your colleagues. Subscribers can upload their reflective accounts at: rcni.com/portfolio . PMID- 27191319 TI - Facilitation of learning: part 2. AB - The previous article in this series of 11, Facilitation of learning: part 1, reviewed learning theories and how they relate to clinical practice. Developing an understanding of these theories is essential for mentors and practice teachers to enable them to deliver evidence-based learning support. This is important given that effective learning support is dependent on an educator who possesses knowledge of their specialist area as well as the relevent tools and methods to support learning. The second domain of the Nursing and Midwifery Council's Standards to Support Learning and Assessment in Practice relates to the facilitation of learning. To fulfil this domain, mentors and practice teachers are required to demonstrate their ability to recognise the needs of learners and provide appropriate support to meet those needs. This article expands on some of the discussions from part 1 of this article and considers these from a practical perspective, in addition to introducing some of the tools that can be used to support learning. PMID- 27191320 TI - Neutropenic sepsis: prevention, identification and treatment. AB - Chemotherapy-induced neutropenia may result in significant physical, social and emotional consequences for patients receiving anticancer therapy. Chemotherapy induced neutropenia also leads to delays in treatment and reductions in dose intensity. In some cases neutropenia may be prevented by the use of granulocyte colony stimulating factor, but it remains one of the most common side effects of chemotherapy. Patients who are neutropenic have a reduced ability to fight infection and are at increased risk of developing neutropenic sepsis. Nurses need to be able to recognise the signs and symptoms of neutropenic sepsis to ensure early diagnosis and treatment. There are evidence-based pathways for the treatment of patients with neutropenic sepsis and nurses have the potential to develop services and initiatives to support best practice for this group of patients. PMID- 27191321 TI - Medication errors. AB - Medication errors are one of the most common causes of preventable harm to patients, and result in a financial burden on the NHS. PMID- 27191322 TI - When one door closes. AB - We probably all know someone who has been made redundant from their job. It could even have happened to you. PMID- 27191323 TI - Platforms for progression. AB - Nurses looking for jobs could do worse than spend more time on their smartphones, because employers are increasingly using social media to recruit staff. PMID- 27191325 TI - On the move. AB - Promotions / new appointments. PMID- 27191326 TI - Student life - Which path should you take? AB - Last year's Shape of Caring review highlighted the alarming fact that at least 20% of nursing students are dropping out of their studies. PMID- 27191327 TI - Attorneys and Physicians. PMID- 27191328 TI - Problems+Solutions. AB - Readers are invited to submit questions relating to problem cases. Inquiries will be answered by qualified consultants and replies forwarded by mail promptly. Selected problems and solutions are published every month in this section. PMID- 27191329 TI - The Medical Bookshelf. PMID- 27191330 TI - THE airway in systemic disease. PMID- 27191331 TI - Nasal manifestations of systemic disease. PMID- 27191333 TI - Primary Care Digest. PMID- 27191335 TI - Whole-Genome Analysis of Cryptococcus gattii, Southeastern United States. AB - Cryptococcus gattii is a recognized pathogenic fungus along the Pacific coast of the United States from California to Washington. Here we report that C. gattii may also be endemic to the southeastern United States and has probably been present there longer than in the Pacific Northwest. PMID- 27191336 TI - Initial Development and Psychometric Properties of a New Measure of Substance Use Disorder "Recovery Progression": The Recovery Progression Measure (RPM). AB - There is a growing literature around substance use disorder treatment outcomes measures. Various constructs have been suggested as being appropriate for measuring recovery outcomes, including "recovery capital" and "treatment progression." However, these previously proposed constructs do not measure changes in psychosocial functioning during the recovery process. Therefore, a new psychometric assessment, the "Recovery Progression Measure" (RPM), has been developed to measure this recovery oriented psychosocial change. AIMS: The aims of this study were to evaluate the reliability and factor structure of the RPM via data collected from 2218 service users being treated for their substance dependence. METHOD: Data were collected from service users accessing the Breaking Free Online (BFO) substance use disorder treatment and recovery program, which has within its baseline assessment a 36-item psychometric measure previously developed by the authors to assess the six areas of functioning described in the RPM. Reliability analyses and exploratory factor analyses (EFA) were conducted to examine the underlying factor structure of the RPM measure. RESULTS: Internal reliability of the RPM measure was found to be excellent (alpha > .70) with the overall assessment to have reliability alpha = .89, with item-total correlations revealing moderate-excellent reliability of individual items. EFA revealed the RPM to contain an underlying factor structure of eight components. DISCUSSION: This study provides initial data to support the reliability of the RPM as a recovery measure. Further work is now underway to extend these findings, including convergent and predictive validity analyses. PMID- 27191337 TI - Exploring structure and interactions of the bacterial adaptor protein YjbH by crosslinking mass spectrometry. AB - Adaptor proteins assist proteases in degrading specific proteins under appropriate conditions. The adaptor protein YjbH promotes the degradation of an important global transcriptional regulator Spx, which controls the expression of hundreds of genes and operons in response to thiol-specific oxidative stress in Bacillus subtilis. Under normal growth conditions, the transcription factor is bound to the adaptor protein and therefore degraded by the AAA+ protease ClpXP. If this binding is alleviated during stress, the transcription factor accumulates and turns on genes encoding stress-alleviating proteins. The adaptor protein YjbH is thus a key player involved in these interactions but its structure is unknown. To gain insight into its structure and interactions we have used chemical crosslinking mass spectrometry. Distance constraints obtained from the crosslinked monomer were used to select and validate a structure model of YjbH and then to probe its interactions with other proteins. The core structure of YjbH is reminiscent of DsbA family proteins. One lysine residue in YjbH (K177), located in one of the alpha-helices outside the thioredoxin fold, crosslinked to both Spx K99 and Spx K117, thereby suggesting one side of the YjbH for the interaction with Spx. Another lysine residue that crosslinked to Spx was YjbH K5, located in the long and presumably very flexible N-terminal arm of YjbH. Our crosslinking data lend support to a model proposed based on site-directed mutagenesis where the YjbH interaction with Spx can stabilize and present the C terminal region of Spx for protease recognition and proteolysis. Proteins 2016; 84:1234-1245. (c) 2016 Wiley Periodicals, Inc. PMID- 27191338 TI - Fractal features and surface micromorphology of diamond nanocrystals. AB - This paper analyses the three-dimensional (3-D) surface texture of growing diamond nanocrystals on Au thin films as catalyst on p-type Si substrate using hot filament chemical vapour deposition (HFCVD). Rutherford backscattering spectrometry (RBS), atomic force microscopy (AFM), Raman, X-ray diffraction (XRD) and scanning electron microscopy (SEM) analyses were applied also to characterize the 3-D surface texture data in connection with the statistical, and fractal analyses. This type of 3-D morphology allows a deeper understanding of structure/property relationships and surface defects in prepared samples. Our results indicate a promising way for preparing high-quality diamond nanocrystals on Au thin films as catalyst on p-type Si substrate via HFCVD method. PMID- 27191339 TI - Can the Afinion HbA1c Point-of-Care instrument be an alternative method for the Tosoh G8 in the case of Hb-Tacoma? AB - BACKGROUND: Hb-variant interference when reporting HbA1c has been an ongoing challenge since HbA1c was introduced to monitor patients with diabetes mellitus. Most Hb-variants show an abnormal chromatogram when cation-exchange HPLC is used for the determination of HbA1c. Unfortunately, the Tosoh G8 generates what appears to be normal chromatogram in the presence of Hb-Tacoma, yielding a falsely high HbA1c value. The primary aim of the study was to investigate if the Afinion HbA1c point-of-care (POC) instrument could be used as an alternative method for the Tosoh G8 when testing for HbA1c in the presence of Hb-Tacoma. METHODS: Whole blood samples were collected in K2EDTA tubes from individuals homozygous for HbA (n = 40) and heterozygous for Hb-Tacoma (n = 20). Samples were then immediately analyzed with the Afinion POC instrument. After analysis, aliquots of each sample were frozen at -80 degrees C. The frozen samples were shipped on dry ice to the European Reference Laboratory for Glycohemoglobin (ERL) and analyzed with three International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and National Glycohemoglobin Standardization Program (NGSP) Secondary Reference Measurement Procedures (SRMPs). The Premier Hb9210 was used as the reference method. RESULTS: When compared to the reference method, samples with Hb-Tacoma yielded mean relative differences of 31.8% on the Tosoh G8, 21.5% on the Roche Tina-quant Gen. 2 and 16.8% on the Afinion. CONCLUSIONS: The Afinion cannot be used as an alternative method for the Tosoh G8 when testing for HbA1c in the presence of Hb-Tacoma. PMID- 27191340 TI - Histamine H2 receptor blockade augments blood pressure responses to acute submaximal exercise in males. AB - Histamine is a potent vasodilator that has been found to increase during exercise. We tested the hypothesis that histamine would attenuate blood pressure (BP), cardiac output (CO), and vascular resistance responses to short-term, submaximal dynamic exercise during H2 receptor blockade. Fourteen healthy men (20 29 years of age) were studied. Systolic (SBP), diastolic (DBP), and mean arterial (MAP) BP and heart rate (HR) were assessed at rest and during the last minute of 10 min of submaximal cycling exercise (60% of peak oxygen consumption) in the absence and presence of histamine H2 receptor blockade (ranitidine, 300 mg). Stroke volume (SV) (impedance cardiography) and plasma norepinephrine (NE) were measured, and CO, rate * pressure product (RPP), and total peripheral resistance (TPR) were calculated. Plasma levels of histamine were also measured. H2 blockade had no effects on any variables at rest. During exercise, SBP (184 +/- 3 mm Hg vs. 166 +/- 2 mm Hg), MAP (121 +/- 2 mm Hg vs. 112 +/- 5 mm Hg), and RPP (25.9 +/ 0.8 * 10(3) mm Hg.beats/min vs. 23.5 +/- 0.8 * 10(3) mm Hg/beats.min) were greater during blocked conditions (P < 0.05), and an interaction was observed for TPR. SV, DBP, HR, and NE levels were unaffected by blockade. Plasma histamine increased from 1.83 +/- 0.14 ng/mL at rest to 2.33 +/- 0.23 ng/mL during exercise (P < 0.05) and was not affected by H2 blockade (1.56 +/- 0.23 ng/mL vs. 1.70 +/- 0.24 ng/mL). These findings suggest that, during submaximal exercise, histamine attenuates BP, vascular resistance, and the work of the heart via activation of H2 receptors and that these effects occurred primarily in the vasculature and not in the myocardium. PMID- 27191342 TI - Microscale air quality impacts of distributed power generation facilities. AB - The electric system is experiencing rapid growth in the adoption of a mix of distributed renewable and fossil fuel sources, along with increasing amounts of off-grid generation. New operational regimes may have unforeseen consequences for air quality. A three-dimensional microscale chemical transport model (CTM) driven by an urban wind model was used to assess gaseous air pollutant and particulate matter (PM) impacts within ~10 km of fossil-fueled distributed power generation (DG) facilities during the early afternoon of a typical summer day in Houston, TX. Three types of DG scenarios were considered in the presence of motor vehicle emissions and a realistic urban canopy: (1) a 25-MW natural gas turbine operating at steady state in either simple cycle or combined heating and power (CHP) mode; (2) a 25-MW simple cycle gas turbine undergoing a cold startup with either moderate or enhanced formaldehyde emissions; and (3) a data center generating 10 MW of emergency power with either diesel or natural gas-fired backup generators (BUGs) without pollution controls. Simulations of criteria pollutants (NO2, CO, O3, PM) and the toxic pollutant, formaldehyde (HCHO), were conducted assuming a 2 hr operational time period. In all cases, NOx titration dominated ozone production near the source. The turbine scenarios did not result in ambient concentration enhancements significantly exceeding 1 ppbv for gaseous pollutants or over 1 ug/m(3) for PM after 2 hr of emission, assuming realistic plume rise. In the case of the datacenter with diesel BUGs, ambient NO2 concentrations were enhanced by 10-50 ppbv within 2 km downwind of the source, while maximum PM impacts in the immediate vicinity of the datacenter were less than 5 ug/m(3). IMPLICATIONS: Plausible scenarios of distributed fossil generation consistent with the electricity grid's transformation to a more flexible and modernized system suggest that a substantial amount of deployment would be required to significantly affect air quality on a localized scale. In particular, natural gas turbines typically used in distributed generation may have minor effects. Large banks of diesel backup generators such as those used by data centers, on the other hand, may require pollution controls or conversion to natural gas-fired reciprocal internal combustion engines to decrease nitrogen dioxide pollution. PMID- 27191343 TI - Influence of disability type on upper-limb motor skills. AB - This study was carried out in order to determine the effect of physical disability (paraplegia) and sensory disability (deafness) on motor skills of the upper limbs. Studies were distinguished by two parameters: the nature of the control curve (sine or random) and the magnitude of the isometric force exerted on the lever (10 N, 20 N, 40 N, 80 N). A comparison of the quality of manual force control in a visual detection task among groups of people with sensory disability (deaf), people with physical disability (paraplegic) and people without disability showed differences among those groups. Values of force above 20 N create conditions of lower quality of control and of direction of force exertion outside the body. At the same time, the study proved that people with some types of disability can perform certain work tasks as effectively as people without disability. PMID- 27191345 TI - Cost of dose escalation in people with rheumatoid arthritis treated with tumour necrosis factor inhibitors across Europe. AB - OBJECTIVES: The aim of this study was to calculate the marginal cost of dose escalation in people with rheumatoid arthritis treated with tumour necrosis factor (TNF) inhibitors across Europe. METHODS: The proportion of people who escalate their dose of TNF inhibitor and the average percentage increase in TNF inhibitor cost associated with escalators versus non-escalators was calculated from previously published estimates, weighted by the sample size for each study. The number of people with rheumatoid arthritis treated with TNF inhibitors and the corresponding total drug sales were obtained for five European countries from Decision Resources' Pharmacor Market Forecast. Method 1 assumed that total sales of a TNF inhibitor represented the cost of an escalator multiplied by the number of escalators plus the cost of a non-escalator multiplied by the number of non escalators. Method 2 assumed that the drug cost per day used to forecast total sales was calculated using the dose of TNF inhibitor used by non-escalators. The marginal cost of TNF inhibitor dose escalation was estimated by multiplying the difference in cost between escalators and non-escalators by the number of escalators. RESULTS: The estimated increase in TNF inhibitor costs associated with dose escalation in people with rheumatoid arthritis across five European countries (Germany, France, UK, Spain and Italy) was ?51.5-54.4 million for adalimumab, ?44.8-52.8 million for infliximab and ?5.8-5.9 million for etanercept. CONCLUSIONS: Dose escalation of the TNF inhibitors adalimumab, etanercept and infliximab in people with rheumatoid arthritis has resulted in an increase in TNF inhibitor costs across five European countries. PMID- 27191346 TI - Salmonella Typhimurium methionine sulfoxide reductase A (MsrA) prefers TrxA in repairing methionine sulfoxide. AB - Intraphagocytic survival of Salmonella Typhimurium (ST) depends (at least in part) upon its ability to repair oxidant-damaged macromolecules. Met residues either free or in protein bound form are highly susceptible to phagocyte generated oxidants. Oxidation of Mets leads to Met-SO formation, consequently loss of protein functions that results in cell death. Methionine sulfoxide reductase (Msr) reductively repairs Met-SO to Met in the presence of thioredoxin (trx) and thioredoxin reductase (trxR). Earlier we reported that methionine sulfoxide reductase A (msrA) gene deletion strain of ST suffered oxidative stress.[1] Thioredoxin system of ST comprises of two thioredoxins (trxA and trxC) and one thioredoxin reductase (trxB). Preferred trx utilized in MsrA-mediated repair of Met-SO is not known. In current study, we cloned, expressed, and purified ST TrxA, TrxB, TrxC, and MsrA in recombinant forms. The migration of TrxA, TrxB, TrxC, and MsrA proteins was approximately 10, 36, 16, and 26 kDa on SDS-gels. The nicotinamide adenine dinucleotide phosphate hydrogen (NADPH)-linked reductase assays interpreted that MsrA utilized two times more NADPH for the reduction of S-methyl p-tolyl sulfoxide when TrxA was included in the assays as compared to TrxC. PMID- 27191347 TI - Catalytic Access to Alkyl Bromides, Chlorides and Iodides via Visible Light Promoted Decarboxylative Halogenation. AB - Herein is reported the catalytic, visible light-promoted, decarboxylative halogenation (bromination, chlorination, and iodination) of aliphatic carboxylic acids. This operationally-simple reaction tolerates a range of functional groups, proceeds at room temperature, and is redox neutral. By employing an iridium photocatalyst in concert with a halogen atom source, the use of stoichiometric metals such as silver, mercury, thallium, and lead can be circumvented. This reaction grants access to valuable synthetic building blocks from the large pool of cheap, readily available carboxylic acids. PMID- 27191344 TI - Arylfluorosulfates Inactivate Intracellular Lipid Binding Protein(s) through Chemoselective SuFEx Reaction with a Binding Site Tyr Residue. AB - Arylfluorosulfates have appeared only rarely in the literature and have not been explored as probes for covalent conjugation to proteins, possibly because they were assumed to possess high reactivity, as with other sulfur(VI) halides. However, we find that arylfluorosulfates become reactive only under certain circumstances, e.g., when fluoride displacement by a nucleophile is facilitated. Herein, we explore the reactivity of structurally simple arylfluorosulfates toward the proteome of human cells. We demonstrate that the protein reactivity of arylfluorosulfates is lower than that of the corresponding aryl sulfonyl fluorides, which are better characterized with regard to proteome reactivity. We discovered that simple hydrophobic arylfluorosulfates selectively react with a few members of the intracellular lipid binding protein (iLBP) family. A central function of iLBPs is to deliver small-molecule ligands to nuclear hormone receptors. Arylfluorosulfate probe 1 reacts with a conserved tyrosine residue in the ligand-binding site of a subset of iLBPs. Arylfluorosulfate probes 3 and 4, featuring a biphenyl core, very selectively and efficiently modify cellular retinoic acid binding protein 2 (CRABP2), both in vitro and in living cells. The X-ray crystal structure of the CRABP2-4 conjugate, when considered together with binding site mutagenesis experiments, provides insight into how CRABP2 might activate arylfluorosulfates toward site-specific reaction. Treatment of breast cancer cells with probe 4 attenuates nuclear hormone receptor activity mediated by retinoic acid, an endogenous client lipid of CRABP2. Our findings demonstrate that arylfluorosulfates can selectively target single iLBPs, making them useful for understanding iLBP function. PMID- 27191348 TI - Claudins and mineral metabolism. AB - PURPOSE OF REVIEW: The tight junction conductance made of the claudin-based paracellular channel is important in the regulation of calcium and magnesium reabsorption in the kidney. This review describes recent findings of the structure, the function, and the physiologic regulation of claudin-14, claudin 16, and claudin-19 channels that through protein interactions confer calcium and magnesium permeability to the tight junction. RECENT FINDINGS: Mutations in two tight junction genes - claudin-16 and claudin-19 - cause the inherited renal disorder familial hypomagnesemia with hypercalciuria and nephrocalcinosis. A recent genome-wide association study has identified claudin-14 as a major risk gene of hypercalciuric nephrolithiasis. The crystal structure of claudin-19 has recently been resolved allowing the reconstruction of a claudin assembly model from cis-dimers made of claudin-16 and claudin-19 interaction. MicroRNAs have been identified as novel regulators of the claudin-14 gene. The microRNA-claudin 14 operon is directly regulated by the Ca sensing receptor gene in response to hypercalcemia. SUMMARY: The paracellular pathway in the kidney is particularly important for mineral metabolism. Three claudin proteins - claudin-14, claudin 16, and claudin-19 - contribute to the structure and function of this paracellular pathway. Genetic mutations and gene expression changes in these claudins may lead to alteration of the paracellular permeability to calcium and magnesium, ultimately affecting renal mineral metabolism. PMID- 27191350 TI - Role of mesenchymal stem cells in kidney injury and fibrosis. AB - PURPOSE OF REVIEW: Multiple studies have established the beneficial role of mesenchymal stem cell (MSC) therapy for kidney injury. In this review we will discuss the recent identification of Gli1 as a marker for perivascular MSC and the role of this cell population in kidney fibrosis. RECENT FINDINGS: Recent studies demonstrate that expression of the hedgehog transcriptional activator Gli1 specifically marks perivascular MSC. Genetic fate tracing of MSC in kidney injury revealed their contribution to the myofibroblast pool whereas ablation of MSC reduced kidney fibrosis. Furthermore, strong evidence suggests that pharmacologically targeting Gli proteins inhibits cell-cycle progression of myofibroblasts in kidney fibrosis and is a promising therapeutic strategy in chronic kidney disease. SUMMARY: Although there is tremendous excitement about MSC as cellular therapy in kidney injury it has been shown that resident perivascular MSC are a major source of myofibroblasts and a novel therapeutic target in kidney fibrosis. While resident kidney MSC might also be involved in capillary rarefaction after injury and during fibrosis progression their potential role in kidney repair, angiogenesis, and regeneration remains unclear. Further studies are needed to identify the molecular pathways that control the profibrotic versus proregenerative role of resident MSC in kidney injury and repair. PMID- 27191349 TI - Oxalate, inflammasome, and progression of kidney disease. AB - PURPOSE OF REVIEW: Oxalate is an end product of metabolism excreted via the kidney. Excess urinary oxalate, whether from primary or enteric hyperoxaluria, can lead to oxalate deposition in the kidney. Oxalate crystals are associated with renal inflammation, fibrosis, and progressive renal failure. It has long been known that as the glomerular filtration rate becomes reduced in chronic kidney disease (CKD), there is striking elevation of plasma oxalate. Taken together, these findings raise the possibility that elevation of plasma oxalate in CKD may promote renal inflammation and more rapid progression of CKD independent of primary cause. RECENT FINDINGS: The inflammasome has recently been identified to play a critical role in oxalate-induced renal inflammation. Oxalate crystals have been shown to activate the NOD-like receptor family, pyrin domain containing 3 inflammasome (also known as NALP3, NLRP3, or cryopyrin), resulting in release of IL-1beta and macrophage infiltration. Deletion of inflammasome proteins in mice protects from oxalate-induced renal inflammation and progressive renal failure. SUMMARY: The findings reviewed in this article expand our understanding of the relevance of elevated plasma oxalate levels leading to inflammasome activation. We propose that inhibiting oxalate-induced inflammasome activation, or lowering plasma oxalate, may prevent or mitigate progressive renal damage in CKD, and warrants clinical trials. PMID- 27191353 TI - New opportunities for allergen immunotherapy using synthetic peptide immuno regulatory epitopes (SPIREs). AB - INTRODUCTION: Allergen immunotherapy (AIT) reduces allergic rhinoconjunctivitis (ARC) symptoms, but long-term efficacy requires treatment for 3-5 years. Synthetic peptide immuno-regulatory epitopes, a new class of AIT, are allergen peptides with a shorter, more convenient treatment regimen that could potentially have benefits on adherence and outcomes. AREAS COVERED: Phase 2 trials of therapies derived from cat, house dust mite, grass, and ragweed allergen peptides demonstrated significant reduction in ARC symptoms after short-course treatment; improvement was sustained for 18-24 months posttreatment. We conducted a PubMed literature search for clinical publications using the search terms AIT; allergen peptides; ARC; cat, grass, house dust mite, and ragweed allergy; SCIT; SLIT; and synthetic peptides. Expert commentary: Long-term disease modification is a realistic goal of AIT. The inconvenience of conventional AIT regimens negatively impacts long-term persistence and, thus, efficacy. In comparison, SPIREs have a more convenient treatment regimen that could potentially have benefits on adherence and outcomes. PMID- 27191351 TI - Inflammation regulates fibroblast growth factor 23 production. AB - PURPOSE OF REVIEW: Fibroblast growth factor 23 (FGF23) is a hormone secreted by osteocytes and osteoblasts that regulates phosphorus and vitamin D homeostasis. FGF23 levels increase progressively in chronic kidney disease (CKD), and FGF23 excess might be a causal factor of left ventricular hypertrophy, CKD progression and death. Therefore, understanding the molecular mechanisms that control FGF23 production is critical to design therapies to lower FGF23 levels. The present review focuses on the role of inflammatory stimuli on FGF23 regulation and summarizes recent studies that support a novel framework linking inflammation to FGF23 regulation. RECENT FINDINGS: Inflammation and iron deficiency, which are common occurrences in CKD, have emerged as novel FGF23 regulators. Recent findings show that inflammation increases FGF23 production in bone through direct and iron-related indirect mechanisms. In these settings, hypoxia-inducible factor (HIF)-1alpha orchestrates FGF23 transcription in response to inflammation and is primarily responsible for coordinating FGF23 production and cleavage. SUMMARY: We demonstrate that inflammation increases FGF23 production and may contribute to elevated FGF23 levels in CKD. Osseous HIF-1alpha may represent a therapeutic target to lower FGF23 levels in CKD patients and minimize the negative consequences associated with FGF23 excess. PMID- 27191352 TI - Rational Design of Prevascularized Large 3D Tissue Constructs Using Computational Simulations and Biofabrication of Geometrically Controlled Microvessels. AB - A major challenge in the development of clinically relevant 3D tissue constructs is the formation of vascular networks for oxygenation, nutrient supply, and waste removal. To this end, this study implements a multimodal approach for the promotion of vessel-like structures formation in stiff fibrin hydrogels. Computational simulations have been performed to identify the easiest microchanneled configuration assuring normoxic conditions throughout thick cylindrical hydrogels (8 mm height, 6 mm ?), showing that in our configuration a minimum of three microchannels (600 MUm ?), placed in a non-planar disposition, is required. Using small hydrogel bricks with oxygen distribution equal to the microchanneled configuration, this study demonstrates that among different culture conditions, co-culture of mesenchymal and endothelial cells supplemented with ANG-1 and VEGF leads to the most developed vascular network. Microchanneled hydrogels have been then cultured in the same conditions both statically and in a bioreactor for 7 d. Unexpectedly, the combination between shear forces and normoxic conditions is unable to promote microvascular networks formation in three-channeled hydrogels. Differently, application of either shear forces or normoxic conditions alone results in microvessels outgrowth. These results suggest that to induce angiogenesis in engineered constructs, complex interactions between several biochemical and biophysical parameters have to be modulated. PMID- 27191354 TI - Hematologic Response to Vorinostat Treatment in Relapsed Myeloid Leukemia of Down Syndrome. AB - Children with Down syndrome are at high risk to develop myeloid leukemia (ML-DS). Despite their excellent prognosis, children with ML-DS particularly suffer from severe therapy-related toxicities and for relapsed ML-DS the cure rates are very poor. Here we report the clinical course of one child with ML-DS treated with the histone deacetylase (HDAC) inhibitor vorinostat (suberoylanilide hydroxamic acid) after second relapse. The child had previously received conventional chemotherapy and stem cell transplantation, yet showed a remarkable clinical and hematologic response. Thus, HDAC inhibitor may represent an effective class of drugs for the treatment of ML-DS. PMID- 27191355 TI - Clinical Features of Ocular Sarcoidosis in Patients with Biopsy-proven Pulmonary Sarcoidosis in Serbia. AB - PURPOSE: To analyze clinical characteristics of ocular sarcoidosis in a group of biopsy-proven sarcoid patients treated at the single referral center for sarcoidosis in Serbia. METHODS: A prospective study carried out on 88 biopsy proven sarcoid patients between January 2012 and December 2014. All patients underwent complete ophthalmological examination. RESULTS: Ocular sarcoidosis was present in 32 patients (36.4% of all) and included: eyelid skin lesions (2.3%); orbital inflammation (2.3%); conjunctival lesions (7.9%); anterior uveitis (2.3%); intermediate uveitis (1.1%); posterior uveitis (15.9%); panuveitis (5.7%), and neuro-ophthalmologic manifestations (9.1%). Complications included cataract (20.4%); glaucoma (5.7%); cystoid macular edema (3.4%); epiretinal membrane formation (4.5%); macular atrophy (2.3%); and choroidal neovascularization (1.1%). Binocular visual impairment was present in one patient (1.1%), due to complications of posterior uveitis (macular scars). CONCLUSIONS: Patients in Serbia demonstrated ocular sarcoidosis as the first most common site of extrapulmonary sarcoid manifestations, with more often neuro-ophthalmologic lesions than in other European populations. PMID- 27191356 TI - Assessing the Tongzhi Label: Self-Identification and Public Opinion. AB - Tongzhi is one of several Chinese terms that refer to individuals who are attracted to the same sex. Using data from two different surveys in Hong Kong, this research note examines how the term tongzhi coexists with other terms. We investigate the prevalence of self-identification as tongzhi, and we explore the extent to which using the term tongzhi influences public attitudes toward gay people and gay rights. Activists began popularizing the term tongzhi in the late 1980s, but less than one third of the participants in our 2008 survey of sexual orientation minorities (n = 728) described themselves as tongzhi. Using a split ballot experiment in a 2013 public opinion poll (n = 831), we found that attitudes toward gay people and gay rights were not significantly impacted by whether questions were phrased in terms of tongzhi or the main alternative term tongxinglianzhe. We discuss how our findings can enrich understandings of earlier research and illuminate avenues for future study. PMID- 27191357 TI - Switchover of the Mechanism between Electron Transfer and Hydrogen-Atom Transfer for a Protonated Manganese(IV)-Oxo Complex by Changing Only the Reaction Temperature. AB - Hydroxylation of mesitylene by a nonheme manganese(IV)-oxo complex, [(N4Py)Mn(IV) (O)](2+) (1), proceeds via one-step hydrogen-atom transfer (HAT) with a large deuterium kinetic isotope effect (KIE) of 3.2(3) at 293 K. In contrast, the same reaction with a triflic acid-bound manganese(IV)-oxo complex, [(N4Py)Mn(IV) (O)](2+) -(HOTf)2 (2), proceeds via electron transfer (ET) with no KIE at 293 K. Interestingly, when the reaction temperature is lowered to less than 263 K in the reaction of 2, however, the mechanism changes again from ET to HAT with a large KIE of 2.9(3). Such a switchover of the reaction mechanism from ET to HAT is shown to occur by changing only temperature in the boundary region between ET and HAT pathways when the driving force of ET from toluene derivatives to 2 is around -0.5 eV. The present results provide a valuable and general guide to predict a switchover of the reaction mechanism from ET to the others, including HAT. PMID- 27191358 TI - Editorial: The anxiety of caring and the devaluing of nursing. PMID- 27191359 TI - PET/MRI: A New Frontier in Breast Cancer Imaging. PMID- 27191360 TI - A Community-Oriented Approach to Breast Cancer in a Low-Resource Setting: Improving Awareness, Early Detection and Treatment of Breast Cancer in Tajikistan. AB - Breast cancer is one of the most common cancers and causes of death in females in Tajikistan; yet less than half of the adult women in Tajikistan have heard of breast cancer. Limited access to health care contributes to late stage presentation. We developed a public-private partnership to implement a breast cancer awareness intervention in a low-resource community in Khorog, Tajikistan. We trained local health professionals in clinical breast care and conducted a breast cancer screening and treatment program. The partnership involved visiting USA-based health professionals working alongside local health care providers (HCP) in the continuum of breast care-from education to the diagnostic evaluation and management of detected breast abnormalities. Patient data were collected using a web-based program (VirtualDoc). Twenty-four HCP received didactic and clinical breast examination training. 441 women underwent clinical breast evaluation. 74 (17%) had abnormal exams and underwent additional diagnostic procedures. We identified six (1.4%) cases of breast cancer (all locally advanced) and two women had benign fibroadenomas. All women with cancer underwent modified radical mastectomy, while the fibroadenomas were treated by cosmetically appropriate lumpectomy. Five of six subjects with cancer were previously aware of their breast lump and three had recently seen a family medicine (FM) doctor. Health systems assessment revealed availability of diagnostic equipment but lack of well-trained operators and clinician interpreters. We were successful in integrating clinical breast exams into the routine care of female patients by local FM doctors and in the process, achieved a better understanding of existing risk factors and barriers to breast cancer care. This public-private partnership, leveraging the technical expertise of visiting health professionals, demonstrates how a focused onsite training and awareness program can provide sustained improvements in breast care in a low-resource environment. PMID- 27191362 TI - Corrigendum. PMID- 27191361 TI - A Case of Primary Angiosarcoma of Breast during Pregnancy with Metastasis to the Contralateral Breast: A Potential Diagnostic Pitfall. PMID- 27191363 TI - Investigation on the mechanism of non-photocatalytically TiO2 -induced reactive oxygen species and its significance on cell cycle and morphology. AB - Titanium dioxide (TiO2 ) nanoparticles are widely used in daily human life, and were reported to elicit biological effects such as oxidative stress either generating reactive oxygen species (ROS) or causing cell necrosis without generating ROS, whose underlying molecular mechanisms are not yet known. In this study, the role of dissolved oxygen in TiO2 catalytic activity in dark environment, and long-term cytotoxic effects of TiO2 exposure were investigated. To determine the effect of dissolved oxygen, the anatase-TiO2 nanoparticle suspension was prepared both in deoxygenated and regular MilliQ water, and a ~ 9 fold higher ROS in regular MilliQ samples was observed compared to deoxygenated samples while in the dark, which suggested dissolved oxygen as the driving agent behind the TiO2 catalytic reaction. On the other hand, the differential cell viability and endogenous ROS activity was demonstrated through a sensitive macrophage-based assay, on a dose- and time-dependent manner. Both the cell number and endogenous ROS activity increased with increase in time till 48 h, followed by a reduction at 72 h exposure period. Long-term exposures to these nanoparticles even at low concentrations were found detrimental to cells, where late apoptosis until 48 h and necrosis at 72 h leading to cell death were noted. Late apoptotic events and cell membrane cytoskeletal actin rearrangement observed were hypothesized to be induced by particle-mediated cellular ROS. This in addition to radical generation ability of TiO2 in the dark will help further in better understanding of the toxicity mechanism in cells beyond ROS generation. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27191364 TI - Promoting the immunization neighborhood: Benefits and challenges of pharmacies as additional locations for HPV vaccination. PMID- 27191366 TI - Cutaneous Hemophagocytic Lymphohistiocytosis: Bean Bags From the Bone. PMID- 27191367 TI - Thermoelectric Detection of Multi-Subband Density of States in Semiconducting and Metallic Single-Walled Carbon Nanotubes. AB - Thermoelectric detection of a multi-subband density of states in semiconducting and metallic single-walled carbon nanotubes is demonstrated by scanning the Fermi energy from electron-doped to hole-doped regions. The Fermi energy is systematically controlled by utilizing the strong electric field induced in electric-double-layer transistor configurations, resulting in the optimization of the thermoelectric power factor. PMID- 27191365 TI - Chronic kidney disease in European patients with obstructive sleep apnea: the ESADA cohort study. AB - The cross-sectional relationship of obstructive sleep apnea with moderate to severe chronic kidney disease, defined as an estimated glomerular filtration rate <60 mL min-1 ?1.73 m-2 , was investigated in a large cohort of patients with suspected obstructive sleep apnea studied by nocturnal polysomnography or cardiorespiratory polygraphy. Data were obtained from the European Sleep Apnea Database, where information from unselected adult patients with suspected obstructive sleep apnea afferent to 26 European sleep centres had been prospectively collected. Both the Modification of Diet in Renal Disease and the Chronic Kidney Disease-Epidemiology Collaboration equations were used for the assessment of estimated glomerular filtration rate. The analysed sample included 7700 subjects, 71% male, aged 51.9 +/- 12.5 years. Severe obstructive sleep apnea (apnea-hypopnea index >=30) was found in 34% of subjects. The lowest nocturnal oxygen saturation was 81 +/- 10.2%. Chronic kidney disease prevalence in the whole sample was 8.7% or 6.1%, according to the Modification of Diet in Renal Disease or the Chronic Kidney Disease-Epidemiology Collaboration equations, respectively. Subjects with lower estimated glomerular filtration rate were older, more obese, more often female, had worse obstructive sleep apnea and more co-morbidities (P < 0.001, each). With both equations, independent predictors of estimated glomerular filtration rate <60 were: chronic heart failure; female gender; systemic hypertension; older age; higher body mass index; and worse lowest nocturnal oxygen saturation. It was concluded that in obstructive sleep apnea, chronic kidney disease is largely predicted by co-morbidities and anthropometric characteristics. In addition, severe nocturnal hypoxaemia, even for only a small part of the night, may play an important role as a risk factor for kidney dysfunction. PMID- 27191369 TI - Increased levels of circulating platelet derived microparticles in Crohn's disease patients. AB - OBJECTIVE: Platelet activation is a consistent feature in inflammatory bowel disease. However, the role of circulating platelet derived microparticles (PDMPs) and the effects of disease activity and treatment on their levels has not been clarified yet in this disorder. MATERIAL AND METHODS: Using flow cytometry, we measured platelet derived microparticles and platelet derived microparticles expressing Annexin V in platelet rich plasma from 47 Crohn's disease and 43 ulcerative colitis patients and 24 healthy controls. RESULTS: Crohn's disease patients have greater PDMPs (0.31% +/- 0.07% versus 0.14% +/- 0.04%, p = 0.02) and PDMPs expressing Annexin V (27% +/- 2.6% versus 14.6% +/- 2.7%, p = 0.002) levels in comparison with healthy controls; however, both microparticles levels are not related with disease activity. Crohn's disease patients on 5-ASA therapy show lower levels of PDMPs in comparison with those on no 5-ASA (0.30% +/- 0.07% versus 0.32% +/- 0.09%, p = 0.048). Ulcerative colitis patients have similar PDMPs and PDMPs expressing Annexin V levels, compared to healthy controls (p = 0.06 and p = 0.2, respectively) and there is no correlation of both microparticles expression with disease activity. 5-ASA has no effect on both microparticles levels in ulcerative colitis patients. Anti-TNF-alpha treatment has no effect on study's microparticles expression in Crohn's and ulcerative colitis patients. CONCLUSIONS: Circulating levels of platelet derived microparticles are increased only in Crohn's patients, but they do not correlate with disease activity. 5-ASA treatment is associated with lower levels of PDMPs only in Crohn's, while anti-TNF-alpha treatment does not influence expression of microparticles in inflammatory bowel disease patients. PMID- 27191368 TI - Single-stage resection and microwave ablation for bilobar colorectal liver metastases. AB - BACKGROUND: Patients undergoing liver resection combined with microwave ablation (MWA) for bilobar colorectal metastasis may have similar overall survival to patients who undergo two-stage hepatectomy, but with less morbidity. METHODS: This was a multi-institutional evaluation of patients who underwent MWA between 2003 and 2012. Morbidity (90-day) and mortality were compared between patients who had MWA alone and those who underwent combined resection and MWA (CRA). Mortality and overall survival after CRA were compared with published data on two stage resections. RESULTS: Some 201 patients with bilobar colorectal liver metastasis treated with MWA from four high-volume institutions were evaluated (100 MWA alone, 101 CRA). Patients who had MWA alone were older, but the groups were otherwise well matched demographically. The tumour burden was higher in the CRA group (mean number of lesions 3.9 versus 2.2; P = 0.003). Overall (31.7 versus 15.0 per cent; P = 0.006) and high-grade (13.9 versus 5.0 per cent; P = 0.030) complication rates were higher in the CRA group. Median overall survival was slightly shorter in the CRA group (38.4 versus 42.2 months; P = 0.132) but disease-free survival was similar (10.1 versus 9.3 months; P = 0.525). The morbidity and mortality of CRA compared favourably with rates in the existing literature on two-stage resection, and survival data were similar. CONCLUSION: Single-stage hepatectomy and MWA resulted in survival similar to that following two-stage hepatectomy, with less overall morbidity. PMID- 27191370 TI - Pericarditis Caused by Hyperinvasive Strain of Neisseria meningitidis, Sardinia, Italy, 2015. PMID- 27191371 TI - Use of alphav Integrin Linked to GFP to Image Molecular Dynamics in Trafficking Cancer-Cell Emboli. AB - Human osteosarcoma cells with an alphav integrin green fluorescent protein (GFP) fusion gene were previously established and imaged in vitro and in vivo. In the present study, we imaged the interaction of alphav integrin-GFP in osteosarcoma cells and collagen fibers in vascular-trafficking osteosarcoma emboli in nude mice. Human 143B osteosarcoma cells, expressing alphav integrin-GFP, were injected by a vascular route in an abdominal skin flap in nude mice. Osteosarcoma cells were fluorescently imaged in the epigastric cranialis vein in the abdominal skin flap by confocal microscopy. Collagen fibers were imaged in reflectance mode. At early stages of tumor embolus-formation, cancer cells adhered firmly to each other, diffusely expressing alphav integrin-GFP. Two weeks after injection, collagen fiber scaffolds were visualized at the margins of tumor emboli or within them. Four weeks after injection, cancer cells invading from emboli were strongly expressing alphav integrin-GFP, and were aligned along collagen fibers. The results suggest alphav integrin and collagen fiber scaffolds are important for tumor embolus formation, which are potential seeds of metastasis. J. Cell. Biochem. 118: 26-30, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27191372 TI - Work Environment and Its Relationship to Quality Improvement: Health Care Providers' Perspectives. AB - There is a gap in understanding how work environment contributes to hospitals' readiness for quality improvement (QI) in developing countries; thus, diagnosing work environment problems in health care organizations is the initial step in designing strategies for QI in organizations. This study examines the relationship between nurses' and physicians' perspectives of the work environments and hospitals' climate for QI. Study results indicate that work environment is positively associated with hospitals' readiness for QI. PMID- 27191373 TI - Treatment Options for Veterans With Posttraumatic Stress Disorder. PMID- 27191374 TI - Leveraging respiratory organ motion for non-invasive tumor treatment devices: a feasibility study. AB - In noninvasive abdominal tumor treatment, research has focused on minimizing organ motion either by gating, breath holding or tracking of the target. The paradigm shift proposed in this study takes advantage of the respiratory organ motion to passively scan the tumor. In the proposed self-scanning method, the focal point of the HIFU device is held fixed for a given time, while it passively scans the tumor due to breathing motion. The aim of this paper is to present a treatment planning method for such a system and show by simulation its feasibility. The presented planning method minimizes treatment time and ensures complete tumor ablation under free-breathing. We simulated our method on realistic motion patterns from a patient specific statistical respiratory model. With our method, we achieved a shorter treatment time than with the gold-standard motion-compensation approach. The main advantage of the proposed method is that electrically steering of the focal spot is no longer needed. As a consequence, it is much easier to find an optimal solution for both avoiding near field heating and covering the whole tumor. However, the reduced complexity on the beam forming comes at the price of an increased complexity on the planning side as well as a reduced efficiency in the energy distribution. Although we simulate the approach on HIFU, the idea of self-scanning passes over to other tumor treatment modalities such as proton therapy or classical radiation therapy. PMID- 27191376 TI - Visible-Light-Assisted Photocatalytic Reduction of Nitroaromatics by Recyclable Ni(II)-Porphyrin Metal-Organic Framework (MOF) at RT. AB - A microporous Ni(II)-porphyrin metal-organic framework (MOF), [Ni3(Ni-HTCPP)2(MU2 H2O)2(H2O)4(DMF)2].2DMF, (MOF1) (where, Ni-HTCPP = 5,10,15,20-tetrakis(4 benzoate) porphyrinato-Ni(II)) has been synthesized by the solvothermal route. Single-crystal X-ray diffraction study of 1 reveals a 2D network structure constituted by Ni3 cluster and [Ni-HTCPP](3-) metalloligand having (3, 6) connected binodal net with {4(3)}2{4(6).6(6).8(3)}-kgd net topology. The 2D layers are further stacked together through pi-pi interactions between the porphyrin linkers to generate a 3D supramolecular framework which houses 1D channels with dimension of ~5.0 * 9.0 A(2) running along the crystallographic a axis. Visible-light-assisted photocatalytic investigation of MOF1 for heterogeneous reduction of various nitroaromatics at room temperature resulted in the corresponding amines with high yield and selectivity. On the contrary, the Ni(II)-centered porphyrin tetracarboxylic acid [Ni-H4TCPP] metalloligand does not show the photocatalytic activity under similar conditions. The remarkably high catalytic performance of MOF1 over [Ni-H4TCPP] metalloligand has been attributed due to cooperative catalysis involving the Ni-centered porphyrin secendary building units (SBUs) and the Ni3-oxo node. Further, the MOF1 was recycled and reused up to three cycles without any significant loss of catalytic activity as well as structural rigidity. To the best of our knowledge, MOF1 represents the first example of MOF based on 3d metal ion exhibiting visible-light-assisted reduction of nitroaromatics under mild conditions without the assistance of noble metal cocatalysts. PMID- 27191375 TI - Help-Seeking Behaviors Among Active-Duty Military Personnel: Utilization of Chaplains and Other Mental Health Service Providers. AB - Military chaplains not only conduct religious services, but also provide counseling and spiritual support to military service members, operating as liaisons between soldiers and mental health professionals. In this study, active duty soldiers (N = 889) reported help-seeking behaviors and mental health. Using logistic regressions, we describe the issues for which soldiers reported seeking help, then outline the characteristics of those who are most likely to seek help from a chaplain. Of the soldiers who sought help from a chaplain within the previous year, 29.9% reported high levels of combat exposure, 50.8% screened positive for depression, 39.1% had probable PTSD, and 26.6% screened positive for generalized anxiety disorder. The participant's unit firing on the enemy, personally firing on the enemy, and seeing dead bodies or human remains predicted seeing a chaplain. Future research should examine ways to engage soldiers who have had more combat experiences with the chaplain community to address spiritual issues. PMID- 27191377 TI - The Recaptured Scale Technique: A Method for Testing the Structural Robustness of Personality Scales. AB - Tellegen and Waller advocated a complex and time-consuming scale construction method that they called "exploratory test construction." Scales that are constructed by this method-such as the Multidimensional Personality Questionnaire (MPQ)-are presumed to be more "psychologically coherent" and "robust" than scales constructed by other means. Using a novel procedure that we call the "recaptured scale technique," we tested this conjecture by conducting a megafactor analysis on data from the 411 adult participants of the Minnesota Study of Twins Reared Apart who completed the MPQ, the MMPI, and the CPI. We extracted and obliquely rotated 21 factors from a matrix of gender-corrected tetrachoric correlations for the 1,102 nonredundant items of the three omnibus inventories. Robustness of the 11 MPQ scales was assessed by the degree to which these factors recaptured the MPQ item groupings. Our results showed that nine factors were clearly recognizable as MPQ scales and two additional factors represented a bifurcation of an MPQ scale. A higher-order factor analysis of all 21 factor scales yielded five factors that clearly resembled the Big Five. Our results provide strong support for (a) the method of exploratory test construction, (b) the structural robustness of most MPQ scales, and PMID- 27191379 TI - Is Poor Sleep Quality Associated With Greater Disability in Patients With Multiple Sclerosis? AB - Poor sleep is a serious burden for patients with multiple sclerosis (MS). The aim of this study is to assess whether the association between sleep quality and disability in MS patients is direct or mediated by depression, pain, and fatigue. We collected data from 152 patients with MS who filled out the Pittsburgh Sleep Quality Index, the Hospital Anxiety and Depression Scale, the Multidimensional Fatigue Inventory and one item of the Short Form-36 regarding pain. The relationship between poor sleep and disability was found to be indirect, mediated by depression (p < 0.05), pain (p < 0.001) and physical fatigue (p < 0.01). Treatment of sleep disturbances may have beneficial effects beyond improving sleep. It may reduce depression, pain, and physical fatigue, which in turn may lessen disability. PMID- 27191380 TI - Extended Human-to-Human Transmission during a Monkeypox Outbreak in the Democratic Republic of the Congo. AB - A >600% increase in monkeypox cases occurred in the Bokungu Health Zone of the Democratic Republic of the Congo during the second half of 2013; this increase prompted an outbreak investigation. A total of 104 possible cases were reported from this health zone; among 60 suspected cases that were tested, 50 (48.1%) cases were confirmed by laboratory testing, and 10 (9.6%) tested negative for monkeypox virus (MPXV) infection. The household attack rate (i.e., rate of persons living with an infected person that develop symptoms of MPXV infection) was 50%. Nine families showed >1 transmission event, and >6 transmission events occurred within this health zone. Mean incubation period was 8 days (range 4-14 days). The high attack rate and transmission observed in this study reinforce the importance of surveillance and rapid identification of monkeypox cases. Community education and training are needed to prevent transmission of MPXV infection during outbreaks. PMID- 27191381 TI - Enhancing the Activity of Peptide-Based Artificial Hydrolase with Catalytic Ser/His/Asp Triad and Molecular Imprinting. AB - In this study, an artificial hydrolase was developed by combining the catalytic Ser/His/Asp triad with N-fluorenylmethoxycarbonyl diphenylalanine (Fmoc-FF), followed by coassembly of the peptides into nanofibers (CoA-HSD). The peptide based nanofibers provide an ideal supramolecular framework to support the functional groups. Compared with the self-assembled catalytic nanofibers (SA-H), which contain only the catalytic histidine residue, the highest activity of CoA HSD occurs when histidine, serine, and aspartate residues are at a ratio of 40:1:1. This indicates that the well-ordered nanofiber structure and the synergistic effects of serine and aspartate residues contribute to the enhancement in activity. Additionally, for the first time, molecular imprinting was applied to further enhance the activity of the peptide-based artificial enzyme (CoA-HSD). p-NPA was used as the molecular template to arrange the catalytic Ser/His/Asp triad residues in the proper orientation. As a result, the activity of imprinted coassembled CoA-HSD nanofibers is 7.86 times greater than that of nonimprinted CoA-HSD and 13.48 times that of SA-H. PMID- 27191378 TI - The Cek1-mediated MAP kinase pathway regulates exposure of alpha-1,2 and beta-1,2 mannosides in the cell wall of Candida albicans modulating immune recognition. AB - The Cek1 MAP kinase (MAPK) mediates vegetative growth and cell wall biogenesis in the fungal pathogen Candida albicans. Alterations in the fungal cell wall caused by a defective Cek1-mediated signaling pathway leads to increased beta-1,3-glucan exposure influencing dectin-1 fungal recognition by immune cells. We show here that cek1 cells also display an increased exposure of alpha-1,2 and beta-1,2 mannosides (alpha-M and beta-M), a phenotype shared by strains defective in the activating MAPKK Hst7, suggesting a general defect in cell wall assembly. cek1 cells display walls with loosely bound material as revealed by transmission electron microscopy and are sensitive to tunicamycin, an inhibitor of N glycosylation. Transcriptomal analysis of tunicamycin treated cells revealed a differential pattern between cek1 and wild type cells which involved mainly cell wall and stress related genes. Mapping alpha-M and beta-M epitopes in the mannoproteins of different cell wall fractions (CWMP) revealed an important shift in the molecular weight of the mannan derived from mutants defective in this MAPK pathway. We have also assessed the role of galectin-3, a member of a beta galactoside-binding protein family shown to bind to and kill C. albicans through beta-M recognition, in the infection caused by cek1 mutants. Increased binding of cek1 to murine macrophages was shown to be partially blocked by lactose. Galectin 3(-/-) mice showed increased resistance to fungal infection, although galectin-3 did not account for the reduced virulence of cek1 mutants in a mouse model of systemic infection. All these data support a role for the Cek1-mediated pathway in fungal cell wall maintenance, virulence and antifungal discovery. PMID- 27191383 TI - Fine-Needle Diathermy with Simultaneous Subconjunctival Bevacizumab. AB - PURPOSE: To describe our experience of the use of subconjunctival bevacizumab in conjunction with fine-needle diathermy for the treatment of corneal vascularization. METHODS: Retrospective analysis of cases treated between 2010 and 2013. RESULTS: Those patients with corneal lipid deposition had good results following treatment with 3/5 cases requiring more than one session of treatment. A single patient with severe atopy and multiple previous failed penetrating keratoplasty underwent five sessions of treatment but his third graft subsequently also failed. CONCLUSION: Concurrent use of subconjunctival bevacizumab with FND gives good results in patients with lipid deposition; however, the management of cases with ongoing inflammatory processes is much more challenging. PMID- 27191382 TI - Deep biomarkers of human aging: Application of deep neural networks to biomarker development. AB - One of the major impediments in human aging research is the absence of a comprehensive and actionable set of biomarkers that may be targeted and measured to track the effectiveness of therapeutic interventions. In this study, we designed a modular ensemble of 21 deep neural networks (DNNs) of varying depth, structure and optimization to predict human chronological age using a basic blood test. To train the DNNs, we used over 60,000 samples from common blood biochemistry and cell count tests from routine health exams performed by a single laboratory and linked to chronological age and sex. The best performing DNN in the ensemble demonstrated 81.5 % epsilon-accuracy r = 0.90 with R(2) = 0.80 and MAE = 6.07 years in predicting chronological age within a 10 year frame, while the entire ensemble achieved 83.5% epsilon-accuracy r = 0.91 with R(2) = 0.82 and MAE = 5.55 years. The ensemble also identified the 5 most important markers for predicting human chronological age: albumin, glucose, alkaline phosphatase, urea and erythrocytes. To allow for public testing and evaluate real-life performance of the predictor, we developed an online system available at http://www.aging.ai. The ensemble approach may facilitate integration of multi-modal data linked to chronological age and sex that may lead to simple, minimally invasive, and affordable methods of tracking integrated biomarkers of aging in humans and performing cross-species feature importance analysis. PMID- 27191384 TI - Traceless and Chemoselective Amine Bioconjugation via Phthalimidine Formation in Native Protein Modification. AB - ortho-Phthalaldehyde (OPA) and its derivatives are found to react chemoselectively with amino groups on peptides and proteins rapidly and tracelessly under the physiological condition via formation of phthalimidines, which provides a novel and promising approach when performing bioconjugation on native proteins. The notable advantages of this method over the existing native protein lysine-labeling approaches include a traceless process, a self-reacting, specific and fast reaction, ease of operation, and the ability to use nonhydrolyzable reagents. Its applications have been effectively demonstrated including conjugation of peptides and proteins, and generation of an active PEGlyated l-asparaginase. PMID- 27191385 TI - A Simplified Semiquantitative Meal Bolus Strategy Combined with Single- and Dual Hormone Closed-Loop Delivery in Patients with Type 1 Diabetes: A Pilot Study. AB - BACKGROUND: Single- and dual-hormone closed-loop systems can improve glycemic control and have the potential to reduce carbohydrate-counting burden for patients with type 1 diabetes; however, simplification of meal insulin calculation should not compromise glycemic control. METHODS: We compared in a randomized outpatient pilot trial: (1) a single-hormone closed-loop system accompanied with carbohydrate-content matched boluses versus accompanied with a simplified meal bolus strategy, and (2) a dual-hormone closed-loop system accompanied with carbohydrate-content matched boluses versus accompanied with a simplified meal bolus strategy. Carbohydrate-matched boluses were based on the participant's carbohydrate meal content estimation whereas the simplified strategy involved the selection, by participants, of a semi-quantitative meal carbohydrate-content size: snack, regular, large, or very large meal. Each participant also underwent sensor-augmented pump therapy. Basal insulin delivery was more aggressive with the simplified bolus. The primary outcome was mean sensor glucose level over a 15-h daytime period. RESULTS: Twelve participants were recruited (48.2 +/- 16.0 years old; HbA1c 7.4% +/- 0.9%) to compare the two bolus strategies during single- and dual-hormone closed-loop delivery. A similar mean sensor glucose level (15 h) was achieved with the carbohydrate-matched boluses and simplified strategy using single-hormone (median [interquartile]: 7.6 [7.2-8.1] vs. 8.0 [7.0-8.6] mmol/L; P = 0.90) and dual-hormone closed-loop systems (7.6 [6.7-9.1] vs. 7.0 [6.4-8.2] mmol/L; P = 0.08). Exploratory analyses showed that, as compared with sensor-augmented pump therapy, there was an increased time spent in hypoglycemia with the simplified strategy but not with the carbohydrate-matched boluses. CONCLUSIONS: Though the algorithm employed in this pilot study may lead to an increased risk for hypoglycemia, this strategy has the potential to reduce the carbohydrate-counting burden in patients with type 1 diabetes while generally maintaining adequate glucose control. Longer outpatient studies with an improved algorithm are needed. PMID- 27191386 TI - Targeting the Motion of Shikimate Kinase: Development of Competitive Inhibitors that Stabilize an Inactive Open Conformation of the Enzyme. AB - The large conformational changes observed by Molecular Dynamics simulation studies on the product release in the LID and shikimic acid binding (SB) domains of the shikimate kinase (SK) enzyme have been exploited in the development of reversible competitive inhibitors against SK from Mycobacterium tuberculosis and Helicobacter pylori. This enzyme is a recognized target for antibiotic drug discovery. The reported C5-substituted shikimic acid analogues interact with the dynamic apolar pocket that surrounds the C4 and C5 hydroxyl groups of the natural substrate, cause the opening of the LID and SB domains, and capture the essential arginine far from the ATP binding site as required for catalysis. The 3 nitrobenzyl 3e and 5-benzothiophenyl derivatives 3i proved to be the most potent inhibitors. An ester prodrug of 3i was the most efficient derivative in achieving good in vitro activity against H. pylori, having a MIC value of 4 MUg/mL. PMID- 27191388 TI - Correction: X-Box Binding Protein 1 (XBP1s) Is a Critical Determinant of Pseudomonas aeruginosa Homoserine Lactone-Mediated Apoptosis. AB - [This corrects the article DOI: 10.1371/journal.ppat.1003576.]. PMID- 27191387 TI - Neuroprosthetic Decoder Training as Imitation Learning. AB - Neuroprosthetic brain-computer interfaces function via an algorithm which decodes neural activity of the user into movements of an end effector, such as a cursor or robotic arm. In practice, the decoder is often learned by updating its parameters while the user performs a task. When the user's intention is not directly observable, recent methods have demonstrated value in training the decoder against a surrogate for the user's intended movement. Here we show that training a decoder in this way is a novel variant of an imitation learning problem, where an oracle or expert is employed for supervised training in lieu of direct observations, which are not available. Specifically, we describe how a generic imitation learning meta-algorithm, dataset aggregation (DAgger), can be adapted to train a generic brain-computer interface. By deriving existing learning algorithms for brain-computer interfaces in this framework, we provide a novel analysis of regret (an important metric of learning efficacy) for brain computer interfaces. This analysis allows us to characterize the space of algorithmic variants and bounds on their regret rates. Existing approaches for decoder learning have been performed in the cursor control setting, but the available design principles for these decoders are such that it has been impossible to scale them to naturalistic settings. Leveraging our findings, we then offer an algorithm that combines imitation learning with optimal control, which should allow for training of arbitrary effectors for which optimal control can generate goal-oriented control. We demonstrate this novel and general BCI algorithm with simulated neuroprosthetic control of a 26 degree-of-freedom model of an arm, a sophisticated and realistic end effector. PMID- 27191389 TI - Spiclypeus shipporum gen. et sp. nov., a Boldly Audacious New Chasmosaurine Ceratopsid (Dinosauria: Ornithischia) from the Judith River Formation (Upper Cretaceous: Campanian) of Montana, USA. AB - This study reports on a new ceratopsid, Spiclypeus shipporum gen et sp. nov., from the lower Coal Ridge Member of the Judith River Formation in Montana, USA, which dates to ~76 Ma (upper Campanian). The species is distinguished by rugose dorsal contacts on the premaxillae for the nasals, laterally projecting postorbital horncores, fully fused and anteriorly curled P1 and P2 epiparietals, and a posterodorsally projecting P3 epiparietal. The holotype specimen is also notable for its pathological left squamosal and humerus, which show varied signs of osteomyelitis and osteoarthritis. Although the postorbital horncores of Spiclypeus closely resemble those of the contemporaneous 'Ceratops', the horncores of both genera are nevertheless indistinguishable from those of some other horned dinosaurs, including Albertaceratops and Kosmoceratops; 'Ceratops' is therefore maintained as a nomen dubium. Cladistic analysis recovers Spiclypeus as the sister taxon to the clade Vagaceratops + Kosmoceratops, and appears transitional in the morphology of its epiparietals. The discovery of Spiclypeus adds to the poorly known dinosaur fauna of the Judith River Formation, and suggests faunal turnover within the formation. PMID- 27191390 TI - Investigating Oral Microbiome Profiles in Children with Cleft Lip and Palate for Prognosis of Alveolar Bone Grafting. AB - In this study, we sought to investigate the oral microbiota structure of children with cleft lip and palate (CLP) and explore the pre-operative oral bacterial composition related to the prognosis of alveolar bone grafting. In total, 28 patients (19 boys, 9 girls) with CLP who were scheduled to undergo alveolar bone grafting for the first time were recruited. According to the clinical examination of operative sites at the third month after the operation, the individuals were divided into a non-inflammation group (n = 15) and an inflammation group (n = 13). In all, 56 unstimulated saliva samples were collected before and after the operation. The v3-v4 hypervariable regions of the 16S rRNA gene were sequenced using an Illumina MiSeq sequencing platform. Based on the beta diversity of the operational taxonomic units (OTUs) in the inflammation and non-inflammation samples, the microbial variation in the oral cavity differed significantly between the two groups before and after the operation (P < 0.05). Analysis of the relative abundances of pre-operative OTUs revealed 26 OTUs with a relative abundance higher than 0.01%, reflecting a significant difference of the relative abundance between groups (P < 0.05). According to a principal component analysis of the pre-operative samples, the inflammation-related OTUs included Tannerella sp., Porphyromonas sp., Gemella sp., Moraxella sp., Prevotella nigrescens, and Prevotella intermedia, most of which were enriched in the inflammation group and showed a significant positive correlation. A cross-validated random forest model based on the 26 different OTUs before the operation was able to fit the post operative status of grafted sites and yielded a good classification result. The sensitivity and specificity of this classified model were 76.9% and 86.7%, respectively. These findings show that the oral microbiota profile before alveolar bone grafting may be related to the risk of post-operative inflammation at grafted sites. PMID- 27191391 TI - First Human Cases of Leishmania (Viannia) lainsoni Infection and a Search for the Vector Sand Flies in Ecuador. AB - An epidemiological study of leishmaniasis was performed in Amazonian areas of Ecuador since little information on the prevalent Leishmania and sand fly species responsible for the transmission is available. Of 33 clinical specimens from patients with cutaneous leishmaniasis (CL), causative parasites were identified in 25 samples based on cytochrome b gene analysis. As reported previously, Leishmania (Viannia) guyanensis and L. (V.) braziliensis were among the causative agents identified. In addition, L. (V.) lainsoni, for which infection is reported in Brazil, Bolivia, Peru, Suriname, and French Guiana, was identified in patients with CL from geographically separate areas in the Ecuadorian Amazon, corroborating the notion that L. (V.) lainsoni is widely distributed in South America. Sand flies were surveyed around the area where a patient with L. (V.) lainsoni was suspected to have been infected. However, natural infection of sand flies by L. (V.) lainsoni was not detected. Further extensive vector searches are necessary to define the transmission cycle of L. (V.) lainsoni in Ecuador. PMID- 27191392 TI - The Efficacy of a Nurse-Led Disease Management Program in Improving the Quality of Life for Patients with Chronic Kidney Disease: A Meta-Analysis. AB - BACKGROUND: The impacts of nurse-led disease management programs on the quality of life for patients with chronic kidney disease have not been extensively studied. Furthermore, results of the existing related studies are inconsistent. The focus of the proposed meta-analysis is to evaluate the efficacy of nurse-led disease management programs in improving the quality of life for patients with chronic kidney disease. METHODS: Literature survey was performed to identify the eligible studies from PubMed, Current Nursing and Allied Health Literature, and Cochrane Central Register of Controlled Trials with predefined terms. The outcome measured was quality of life. This meta-analysis was conducted in line with recommendations from the preferred reporting items for systematic reviews and meta-analyses. RESULTS: Eight studies comprising a total of 1520 patients were included in this meta-analysis, with 766 patients assigned to the nurse-led disease management program. Nurse-led disease management improved the quality of life in terms of symptoms, sleep, staff encouragement, pain, general health perception, energy/fatigue, overall health and mental component summary when evaluated 6 weeks after the beginning of intervention. When evaluated 12 weeks later, the quality of life in terms of symptoms, sleep, staff encouragement, energy/fatigue, and physical component summary was improved. Stratified by the modalities of dialysis, similar results of pooled analyses were observed for patients with peritoneal dialysis or hemodialysis, compared with the overall analyses. The results of sensitivity analyses were the same as the primary analyses. The symmetric funnel plot suggested that the possibility of potential publication bias was relatively low. CONCLUSION: Nurse-led disease management program seems effective to improve some parameters of quality of life for patients with chronic kidney disease. However, the seemingly promising results should be cautiously interpreted and generalized and still need to be confirmed through well-designed large-scale prospective randomized controlled trials. PMID- 27191393 TI - Human soluble delta-like 1 homolog exerts antitumor effects in vitro and in vivo. AB - Proteolysis of delta-like 1 homolog (DLK1), a cell-surface transmembrane protein, produces an active soluble form of DLK1 (sDLK1). Both membrane-bound DLK1 and sDLK1 modulate multiple developmental processes including adipogenesis, osteogenesis, chondrogenesis and myogenesis. However, cancer-related functions of DLK1 have not yet been established. We thus evaluated the roles of extracellular sDLK1, comprising six EGF-like domains and juxtamembrane regions, in human pancreatic cancer MIA PaCa-2 cells in vitro and in vivo. We observed that sDLK1 exerted antitumor effects not only in cancer cell migration and anchorage independent cell growth but also in in vivo tumor growth. PMID- 27191394 TI - Known-Groups and Concurrent Validity of the Mandarin Tone Identification Test (MTIT). AB - OBJECTIVE: The Mandarin Tone Identification Test (MTIT) is a new test designed to assess the tone identification abilities of children with hearing impairment (HI). Evidence for reliability and sensitivity has been reported. The present study aimed to evaluate the known-groups and concurrent validity of the MTIT. DESIGN: The MTIT and Mandarin Pediatric Speech Intelligibility test (MPSI) were administered in quiet and in noise conditions. The known-groups validity was evaluated by comparing the performance of the MTIT on children with two different levels of HI. The MPSI was included to evaluate the concurrent validity of the MTIT. STUDY SAMPLE: 81 children with HI were recruited in the present study. They were Mandarin-speaking children with profound HI (mean age = 9; 0, n = 41) and with moderate to severe HI (mean age = 8; 9, n = 40). RESULTS: Scores on the MTIT differed between the two groups with different hearing levels suggesting good known-groups validity. A strong relationship between tone and sentence perception both in quiet and in noise provided preliminary evidence for concurrent validity. CONCLUSIONS: The present study confirmed that the MTIT has good known-groups validity and provided preliminary evidence for concurrent validity. The MTIT could be used to evaluate tone identification ability in children with HI with confidence. PMID- 27191395 TI - Mechanical signatures of microbial biofilms in micropillar-embedded growth chambers. AB - Biofilms are surface-attached communities of microorganisms embedded in an extracellular matrix and are essential for the cycling of organic matter in natural and engineered environments. They are also the leading cause of many infections, for example, those associated with chronic wounds and implanted medical devices. The extracellular matrix is a key biofilm component that determines its architecture and defines its physical properties. Herein, we used growth chambers embedded with micropillars to study the net mechanical forces (differential pressure) exerted during biofilm formation in situ. Pressure from the biofilm is transferred to the micropillars via the extracellular matrix, and reduction of major matrix components decreases the magnitude of micropillar deflections. The spatial arrangement of micropillar deflections caused by pressure differences in the different biofilm strains may potentially be used as mechanical signatures for biofilm characterization. Hence, we submit that micropillar-embedded growth chambers provide insights into the mechanical properties and dynamics of the biofilm and its matrix. PMID- 27191398 TI - Digital microfluidics with a magnetically actuated floating liquid marble. AB - Controlled actuation of a floating liquid marble, a liquid droplet coated with hydrophobic particles floating on another liquid surface, is a potential digital microfluidics platform for the transport of aqueous solution with minimal volume loss. This paper reports our recent investigation on the magnetic actuation of floating liquid marbles filled with magnetic particles. The magnetic force and frictional force acting on the floating liquid marble determine the horizontal movement of the marble. We varied the magnetic flux density, flux density gradient, concentration of magnetic particles and speed of the marble to elucidate the relationship between the acting forces. We subsequently determined the suitable operating conditions for the actuation and derived the scaling laws for the actuation parameters. PMID- 27191397 TI - Emissions and Char Quality of Flame-Curtain "Kon Tiki" Kilns for Farmer-Scale Charcoal/Biochar Production. AB - FLAME CURTAIN BIOCHAR KILNS: Pyrolysis of organic waste or woody materials yields charcoal, a stable carbonaceous product that can be used for cooking or mixed into soil, in the latter case often termed "biochar". Traditional kiln technologies for charcoal production are slow and without treatment of the pyrolysis gases, resulting in emissions of gases (mainly methane and carbon monoxide) and aerosols that are both toxic and contribute to greenhouse gas emissions. In retort kilns pyrolysis gases are led back to a combustion chamber. This can reduce emissions substantially, but is costly and consumes a considerable amount of valuable ignition material such as wood during start-up. To overcome these problems, a novel type of technology, the Kon-Tiki flame curtain pyrolysis, is proposed. This technology combines the simplicity of the traditional kiln with the combustion of pyrolysis gases in the flame curtain (similar to retort kilns), also avoiding use of external fuel for start-up. BIOCHAR CHARACTERISTICS: A field study in Nepal using various feedstocks showed char yields of 22 +/- 5% on a dry weight basis and 40 +/- 11% on a C basis. Biochars with high C contents (76 +/- 9%; n = 57), average surface areas (11 to 215 m(2) g(-1)), low EPA16-PAHs (2.3 to 6.6 mg kg(-1)) and high CECs (43 to 217 cmolc/kg)(average for all feedstocks, mainly woody shrubs) were obtained, in compliance with the European Biochar Certificate (EBC). GAS EMISSION FACTORS: Mean emission factors for the flame curtain kilns were (g kg(-1) biochar for all feedstocks); CO2 = 4300 +/- 1700, CO = 54 +/- 35, non-methane volatile organic compounds (NMVOC) = 6 +/- 3, CH4 = 30 +/- 60, aerosols (PM10) = 11 +/- 15, total products of incomplete combustion (PIC) = 100 +/- 83 and NOx = 0.4 +/- 0.3. The flame curtain kilns emitted statistically significantly (p<0.05) lower amounts of CO, PIC and NOx than retort and traditional kilns, and higher amounts of CO2. IMPLICATIONS: With benefits such as high quality biochar, low emission, no need for start-up fuel, fast pyrolysis time and, importantly, easy and cheap construction and operation the flame curtain technology represent a promising possibility for sustainable rural biochar production. PMID- 27191399 TI - Shape-Encoded Chitosan-Polyacrylamide Hybrid Hydrogel Microparticles with Controlled Macroporous Structures via Replica Molding for Programmable Biomacromolecular Conjugation. AB - Polymeric hydrogel microparticle-based suspension arrays with shape-based encoding offer powerful alternatives to planar and bead-based arrays toward high throughput biosensing and medical diagnostics. We report a simple and robust micromolding technique for polyacrylamide- (PAAm-) based biopolymeric-synthetic hybrid microparticles with controlled 2D shapes containing a potent aminopolysaccharide chitosan as an efficient conjugation handle uniformly incorporated in PAAm matrix. A postfabrication conjugation approach utilizing amine-reactive chemistries on the chitosan shows stable incorporation and retained chemical reactivity of chitosan, readily tunable macroporous structures via simple addition of low content long-chain PEG porogens for improved conjugation capacity and kinetics, and one-pot biomacromolecular assembly via bioorthogonal click reactions with minimal nonspecific binding. We believe that the integrated fabrication-conjugation approach reported here could offer promising routes to programmable manufacture of hydrogel microparticle-based biomacromolecular conjugation and biofunctionalization platforms for a large range of applications. PMID- 27191396 TI - Prevalence and Distribution of Segmentation Errors in Macular Ganglion Cell Analysis of Healthy Eyes Using Cirrus HD-OCT. AB - PURPOSE: To determine the frequency of different types of spectral domain optical coherence tomography (SD-OCT) scan artifacts and errors in ganglion cell algorithm (GCA) in healthy eyes. METHODS: Infrared image, color-coded map and each of the 128 horizontal b-scans acquired in the macular ganglion cell-inner plexiform layer scans using the Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA) macular cube 512 * 128 protocol in 30 healthy normal eyes were evaluated. The frequency and pattern of each artifact was determined. Deviation of the segmentation line was classified into mild (less than 10 microns), moderate (10 50 microns) and severe (more than 50 microns). Each deviation, if present, was noted as upward or downward deviation. Each artifact was further described as per location on the scan and zones in the total scan area. RESULTS: A total of 1029 (26.8%) out of total 3840 scans had scan errors. The most common scan error was segmentation error (100%), followed by degraded images (6.70%), blink artifacts (0.09%) and out of register artifacts (3.3%). Misidentification of the inner retinal layers was most frequent (62%). Upward Deviation of the segmentation line (47.91%) and severe deviation (40.3%) were more often noted. Artifacts were mostly located in the central scan area (16.8%). The average number of scans with artifacts per eye was 34.3% and was not related to signal strength on Spearman correlation (p = 0.36). CONCLUSIONS: This study reveals that image artifacts and scan errors in SD-OCT GCA analysis are common and frequently involve segmentation errors. These errors may affect inner retinal thickness measurements in a clinically significant manner. Careful review of scans for artifacts is important when using this feature of SD-OCT device. PMID- 27191400 TI - Vibrotactile Presentation of Musical Notes to the Glabrous Skin for Adults with Normal Hearing or a Hearing Impairment: Thresholds, Dynamic Range and High Frequency Perception. AB - Presentation of music as vibration to the skin has the potential to facilitate interaction between musicians with hearing impairments and other musicians during group performance. Vibrotactile thresholds have been determined to assess the potential for vibrotactile presentation of music to the glabrous skin of the fingertip, forefoot and heel. No significant differences were found between the thresholds for sinusoids representing notes between C1 and C6 when presented to the fingertip of participants with normal hearing and with a severe or profound hearing loss. For participants with normal hearing, thresholds for notes between C1 and C6 showed the characteristic U-shape curve for the fingertip, but not for the forefoot and heel. Compared to the fingertip, the forefoot had lower thresholds between C1 and C3, and the heel had lower thresholds between C1 and G2; this is attributed to spatial summation from the Pacinian receptors over the larger contactor area used for the forefoot and heel. Participants with normal hearing assessed the perception of high-frequency vibration using 1s sinusoids presented to the fingertip and were found to be more aware of transient vibration at the beginning and/or end of notes between G4 and C6 when stimuli were presented 10dB above threshold, rather than at threshold. An average of 94% of these participants reported feeling continuous vibration between G4 and G5 with stimuli presented 10dB above threshold. Based on the experimental findings and consideration of health effects relating to vibration exposure, a suitable range of notes for vibrotactile presentation of music is identified as being from C1 to G5. This is more limited than for human hearing but the fundamental frequencies of the human voice, and the notes played by many instruments, lie within it. However, the dynamic range might require compression to avoid the negative effects of amplitude on pitch perception. PMID- 27191402 TI - Trait-Based Community Assembly along an Elevational Gradient in Subalpine Forests: Quantifying the Roles of Environmental Factors in Inter- and Intraspecific Variability. AB - Understanding how communities respond to environmental variation is a central goal in ecology. Plant communities respond to environmental gradients via intraspecific and/or interspecific variation in plant functional traits. However, the relative contribution of these two responses to environmental factors remains poorly tested. We measured six functional traits (height, leaf thickness, specific leaf area (SLA), leaf carbon concentration (LCC), leaf nitrogen concentration (LNC) and leaf phosphorus concentration (LPC)) for 55 tree species occurring at five elevations across a 1200 m elevational gradient of subalpine forests in Yulong Mountain, Southwest China. We examined the relative contribution of interspecific and intraspecific traits variability based on community weighted mean trait values and functional diversity, and tested how different components of trait variation respond to different environmental axes (climate and soil variables). Species turnover explained the largest amount of variation in leaf morphological traits (leaf thickness and SLA) across the elevational gradient. However, intraspecific variability explained a large amount of variation (49.3%-76.3%) in three other traits (height, LNC and LPC) despite high levels of species turnover. The detection of limiting similarity in community assembly was improved when accounting for both intraspecific and interspecific variability. Different components of trait variation respond to different environmental axes, especially soil water content and climatic variables. Our results indicate that intraspecific variation is critical for understanding community assembly and evaluating community response to environmental change. PMID- 27191401 TI - The Regulation of para-Nitrophenol Degradation in Pseudomonas putida DLL-E4. AB - Pseudomonas putida DLL-E4 can efficiently degrade para-nitrophenol and its intermediate metabolite hydroquinone. The regulation of para-nitrophenol degradation was studied, and PNP induced a global change in the transcriptome of P. putida DLL-E4. When grown on PNP, the wild-type strain exhibited significant downregulation of 2912 genes and upregulation of 845 genes, whereas 2927 genes were downregulated and 891 genes upregulated in a pnpR-deleted strain. Genes related to two non-coding RNAs (ins1 and ins2), para-nitrophenol metabolism, the tricarboxylic acid cycle, the outer membrane porin OprB, glucose dehydrogenase Gcd, and carbon catabolite repression were significantly upregulated when cells were grown on para-nitrophenol plus glucose. pnpA, pnpR, pnpC1C2DECX1X2, and pnpR1 are key genes in para-nitrophenol degradation, whereas pnpAb and pnpC1bC2bDbEbCbX1bX2b have lost the ability to degrade para-nitrophenol. Multiple components including transcriptional regulators and other unknown factors regulate para-nitrophenol degradation, and the transcriptional regulation of para nitrophenol degradation is complex. Glucose utilization was enhanced at early stages of para-nitrophenol supplementation. However, it was inhibited after the total consumption of para-nitrophenol. The addition of glucose led to a significant enhancement in para-nitrophenol degradation and up-regulation in the expression of genes involved in para-nitrophenol degradation and carbon catabolite repression (CCR). It seemed that para-nitrophenol degradation can be regulated by CCR, and relief of CCR might contribute to enhanced para-nitrophenol degradation. In brief, the regulation of para-nitrophenol degradation seems to be controlled by multiple factors and requires further study. PMID- 27191404 TI - Calcified Cyst in the Spleen. PMID- 27191403 TI - Mothers Make a Difference: Mothers Develop Weaker Bonds with Immature Sons than Daughters. AB - Among mammals, individuals form strong social bonds preferentially with their kin. Differences in these relationships are linked to differential kin availability due to sex-specific dispersal patterns, but there is some indication that differential bonding among sexes already occurs prior to maturation. However, little is known about how these patterns arise during individual development. Here we investigated sex differences in the development of mother offspring bonds in rhesus macaques (Macaca mulatta). Our results revealed that mothers showed sex-biased bonding toward their offspring. Sons had a distinctly higher probability of receiving aggression from their mothers than did daughters in the first year of life, while no differences were found with respect to affiliative interactions. After the first year, probabilities of all affiliative and aggressive behaviours investigated were higher for daughters than for sons, although generally declining. Furthermore, sons spending less time with their mother and receiving more maternal aggression tended to disperse earlier. The results of our study suggest that mothers influence their bonding strength with offspring by interacting less affiliative with sons than daughters. PMID- 27191408 TI - New framework should be given a fair chance. AB - A commitment to ensuring the right staff are in the right place at the right time appears at number nine on the list of ten commitments that underpin the new framework for nursing in England. Others include a pledge to improve education, training and professional development, and a drive to ramp up nursing research with a view to developing a stronger evidence-base for nursing care. PMID- 27191407 TI - Running induces nausea in rats: Kaolin intake generated by voluntary and forced wheel running. AB - Three experiments were conducted showing rats' pica behavior (kaolin clay intake) due to running in activity wheels. The amount of kaolin consumed was a positive function of the available time of voluntary running (20, 40, or 60 min), although this relationship was blunted by a descending (i.e., 60 -> 40 -> 20 min) test series of execution (Experiment 1). Pica was also generated by forced running in a motorized wheel for 60 min as a positive function of the speed of wheel rotations at 98, 185, or 365 m/h, independent of the order of execution (Experiment 2). Voluntary running generated more pica than did forced running at 80 m/h, although the distance travelled in the former condition was 27% lesser than that in the latter condition (Experiment 3). Because kaolin intake is regarded as a reliable measure of nausea in rats, these results show that wheel running, either voluntary or forced, induces nausea in rats. PMID- 27191406 TI - Associations between maternal sense of coherence and controlling feeding practices: The importance of resilience and support in families of preschoolers. AB - Sense of Coherence (SOC) measures an individual's positive, or salutogenic, orientation toward her/his capacities, environment, future, and life. SOC comprises three factors: comprehensibility (the sense of one's own life as ordered and understandable); manageability (the perception of available resources and skills to manage stressors); and meaningfulness (the overall sense that life is filled with meaning and purpose). In numerous studies, SOC has been associated with resilience to stress. However, associations between parental SOC and controlling feeding practices have yet to be studied. This study examines the validity of the SOC 13-item, 3-factor questionnaire, associations between SOC and maternal and child characteristics, and associations between SOC and use of pressuring or restrictive feeding, among mothers of 4-year-olds. 565 mothers (23.5% of foreign origin, 30.3% with overweight/obesity) recruited via the Swedish population registry (response rate: 65%), completed the SOC-13, the Child Feeding Questionnaire (CFQ), and a background questionnaire. The validity of SOC 13 was examined using confirmatory factor analysis; associations with background characteristics and feeding practices were tested with structural equation modeling. SOC-13 validity testing showed acceptable fit (TLI = 0.93, CFI = 0.94, RMSEA = 0.06, SRMR = 0.04) after allowing one pair of error terms to correlate. The Cronbach's alpha for meaningfulness was 0.73, comprehensibility 0.76, and manageability 0.75. SOC increased with mothers' Swedish background and education, and decreased with higher BMI. Child gender, age, and BMI, were not associated with SOC. Lower SOC was associated with controlling practices and with concern about child weight and eating. The associations between SOC and feeding suggest that SOC-related parameters could inform childhood obesity research, and that prevention should address the socioeconomic barriers that parents face in building resilience to stress. PMID- 27191410 TI - Dementia champion is NI nurse of the year. AB - A nurse who transformed dementia care at her trust has been named RCN Northern Ireland nurse of the year. PMID- 27191409 TI - NHS England framework unveiled, with focus on new ways of working. AB - The long-awaited successor to the Compassion in Practice strategy for nurses, midwives and care staff will be launched this week. PMID- 27191411 TI - Patients say they notice when staff are under stress. AB - More than one in five patients said they had been cared for by a visibly stressed nurse in the past year, according to a survey. PMID- 27191412 TI - The case for a new nursing associate role fails to convince students. AB - Nurse academics went head-to-head in a debate last week on the proposed role of nursing associate. PMID- 27191413 TI - Get a grip on nurse supply, MPs tell health bodies. AB - Organisations in charge of NHS staffing have been told to 'get a better grip' on the supply of nurses while they attempt to create a seven-day service. PMID- 27191414 TI - Changing demands of health care require extended nursing roles. AB - Developing the skills of nurses, healthcare assistants and other non-medical staff is the only way the NHS can meet the changing demands of patient care. PMID- 27191415 TI - The spirit of Crimea lives on in trust's sculpture. AB - RCN president Cecilia Anim cut the ribbon on a sculpture commemorating nursing as part of International Nurses Day celebrations in London. PMID- 27191417 TI - Local cancer plan aims to save lives. AB - A plan to save thousands of lives through earlier cancer diagnosis, treatment and care, has been unveiled by NHS England. PMID- 27191418 TI - Bowel surgery recovery scheme proves a success. AB - A targeted recovery programme for patients after having bowel surgery has reduced readmission rates and time spent in hospital. PMID- 27191420 TI - Poor discharge planning causes huge rise in adverse incidents. AB - A sharp rise in discharge-related incidents has prompted the health service ombudsman to issue a warning over patients being unfit to leave hospital. PMID- 27191419 TI - BBC calls in nurse specialist to advise on breast cancer storyline. AB - A clinical nurse specialist in breast care was brought in to advise the BBC on the portrayal of EastEnders' Peggy Mitchell's battle with breast cancer. PMID- 27191421 TI - Nursing's first revalidators give the process an early vote of confidence. AB - Ever since a 2011 Commons health committee report described the nursing regulator's system for ensuring fitness to practise as 'wholly inadequate', the Nursing and Midwifery Council has been gearing up for revalidation. PMID- 27191423 TI - Parents believe better primary care avoids the need for trips to emergency departments. AB - Improving access to primary care will reduce paediatric visits to emergency departments; that is the widely-held view of parents studied in Iowa in the United States. PMID- 27191422 TI - Scientists discover the factor which puts type 2 diabetes into remission following surgery. AB - A gut hormone has been found to restore normal blood glucose levels in people with type 2 diabetes after bariatric surgery. PMID- 27191424 TI - Greater chance of hip replacement failure in last decade, study says. AB - Hip replacements carried out in the last decade have a greater risk of failure, a study found. PMID- 27191425 TI - Protein research offers hope of potential Alzheimer's disease treatment. AB - A protein called IL-33 could hold the key to reversing memory decline in people with Alzheimer's disease. PMID- 27191426 TI - Long-term use of aspirin linked to reduced risk of developing bile duct cancer. AB - The humble aspirin - used regularly and long-term - has the potential to decrease the risk of developing bile duct cancer, new research has found. PMID- 27191427 TI - Controlled drugs. AB - Essential facts Controlled drugs are defined and governed by the Misuse of Drugs Act 1971 and associated regulations. Examples of controlled drugs include morphine, pethidine and methadone. Since 2012, appropriately qualified nurses and midwives can prescribe controlled drugs for medical conditions within their competence. There are some exceptions when treating addiction. PMID- 27191428 TI - How art helps patient care and recovery. PMID- 27191429 TI - Inspirational nurses making a difference. AB - Nurses today perform an astonishing range of roles with energy, imagination and dedication. The three individuals featured here each show a different aspect of nursing: Kirstie Wallace's high-octane job involves managing aircraft and surgeons, Amy Louise Parkes is enabling people with dementia to have more independence, and Anna Richardson has created a ward culture that is open to challenge from patients. PMID- 27191431 TI - Voices - Finally, proof revalidation is not the nightmare many feared, says Janet Finch. AB - I come from an academic background, so am acutely aware of the importance of measuring outcomes in quantifiable terms. I was pleased with our latest revalidation figures because they clearly show that the introduction of the process has been a major success. PMID- 27191430 TI - 'Welsh uprising' gave nurses a true voice. PMID- 27191432 TI - Cultural shift. AB - Many are hailing it as the most significant development since the 1960s. NHS England's General Practice Forward View is a vindication of our call for more investment in primary care nursing. PMID- 27191433 TI - A load of bull. AB - 'How is your vision?' I asked my friend. PMID- 27191435 TI - Readers panel - Justifiable levels of protest. AB - Our experts consider a hot topic of the day. PMID- 27191434 TI - Tell us a story. AB - Want to hear some good news? Of course not. Only bad news sells papers, attracts viewers, gets clicks. Good news is for freesheets and council newsletters. Young people raise cash for puppies? Pass the sick bag. PMID- 27191436 TI - Workplace wisdom. AB - How can I support nurses with work-related mental health issues to better cope with their jobs? PMID- 27191437 TI - Starting out - What do you do when a trip to the loo is anything but bog standard? AB - During my nurse training, I was in a lecture, listening to a woman describing the problems she and her son experienced using the loo in outpatients. Her son had profound multiple learning disabilities, and what should have been a simple matter of gaining access to a toilet became a physical, and emotional, struggle. PMID- 27191441 TI - The best of the week's health-related TV and radio. AB - Our roundup of what's on. PMID- 27191443 TI - Hunt fiddles with his phone, while nurse education bursaries burn. AB - Earlier this month, I sat in the gallery of the House of Commons watching the parliamentary debate over proposed government changes to nurse education funding. This was a phenomenal moment for the #bursaryorbust campaign, highlighting how we are being heard. PMID- 27191444 TI - Call for support to ensure campaign is a roaring success. AB - The #bursaryorbust debate in parliament was a clear example of why we must continue our fight for future students. It is not just the NHS bursary, but Agenda for Change and safe staffing that the government wants to target, and we must draw a line in the sand on this. PMID- 27191445 TI - Awards event is the tip of the outstanding care iceberg. AB - On Friday May 6, the RCNi Nurse Awards 2016 took place at the Westminster Park Plaza Hotel in London. It was a wonderful occasion, and the many examples of excellent work by nurses - individually and in teams - impressed colleagues, families and friends. It was lovely to see nurses praised for their work, and hear how thrilled the finalists were to be shortlisted. PMID- 27191446 TI - Reality of pay rise gives little scope for celebration. AB - Following our recent 1% pay rise, I opened my payslip with excitement, only to be sorely disappointed. PMID- 27191448 TI - Changes to the nursing associate role are no panacea. AB - I find it surprising the number of nurses applauding the proposed changes to the nursing associate role. As well as being hailed as a return to the 'good old days', it is being seen as a stepping stone for healthcare assistants to make the leap to registered nurse, or a way in for the less academically inclined. PMID- 27191449 TI - Government needs to address needs of dying at home patients. AB - Last week was Dying Matters Awareness Week, a campaign to encourage people to talk about their end of life wishes. PMID- 27191450 TI - How to insert a nasogastric tube and check gastric position at the bedside. AB - Rationale and key points A nasogastric tube (NG tube) can be used to aspirate stomach contents or to administer feed, medication or fluid into the stomach. ? A blind technique is used to insert the NG tube through the nostril, along the nasopharynx, through the oesophagus and into the stomach. ? It is important for nurses to be able to recognise problems that may arise when inserting a NG tube blindly, and to know what actions to take if it is suspected that the distal tip of the NG tube is not sitting in the stomach, or they are unable to identify its location. ? Misplacement and subsequent use of a NG tube to administer feed, medication or fluid is a 'never event' ( NHS England Patient Safety Domain 2015 ). Reflective activity Clinical skills articles can help update your practice and ensure it remains evidence based. Apply this article to your practice. Reflect on and write a short account of: 1. How you think this article will change your practice. 2. How you could use this resource to educate your colleagues. Subscribers can update their reflective accounts at rcni.com/portfolio. PMID- 27191451 TI - Assessment and accountability: part 1 - assessment. AB - Assessment in clinical practice is a complex role undertaken by mentors and practice teachers. Therefore, this and the following two articles in this series will explore student assessment in clinical practice and the theoretical concepts that relate to assessment of learning and development. This article examines the importance of assessment and the role of mentors and practice teachers in this activity. Definitions and the purpose of assessment are analysed, in addition to various assessment methods used in clinical practice that relate to the third domain and outcomes of the Nursing and Midwifery Council's Standards to Support Learning and Assessment in Practice on assessment and accountability. PMID- 27191452 TI - Managing resources and reducing waste in healthcare settings. AB - The NHS is under pressure to increase its effectiveness and productivity. Nurses are tasked with delivering effective and efficient care, as well as improving patient safety, experiences and results. The reduction of waste in service delivery, care and treatment can release time and resources for nurses to engage in direct patient care. Nurses have an important role in reducing waste and influencing other professionals in the healthcare environment to increase their efficiency and productivity. PMID- 27191453 TI - Healthy sleep. AB - As a nurse who works permanently on night shifts, I read with interest the CPD article on promoting healthy sleep. PMID- 27191454 TI - Tips for smart leaders. AB - Are you working for a transformational leader? The sort of person the NHS desperately needs who will enthuse and inspire all around them with 100 ideas a minute and boundless energy? Yes? Exhausting isn't it? PMID- 27191456 TI - 'I left the NHS to start a business'. AB - It was December 2011. As I walked through the snow towards the hospital I'd worked at since I was 19, a feeling of despair came over me. I heard myself say out loud: 'I will not be doing this, this time next year.' It took me by surprise - it was not a question, it was a fact. PMID- 27191457 TI - Student life - How to practise effectively. AB - Referring to the Nursing and Midwifery Council Code's second theme - practise effectively; think what effective nursing care means to you and how this has an impact on the essence of quality care. PMID- 27191458 TI - Phenology, reproductive biology and growing degree days of the grapevine 'Isabel' (Vitis labrusca, Vitaceae) cultivated in northeastern Brazil. AB - Phenology and reproductive biology of cultivated species are important for the comprehension of the requirements for fruit and seed production and the management of pollinators. This study aimed to characterise the phenology, reproductive biology and growing degree days of the grapevine 'Isabel' (Vitis labrusca) in northeastern Brazil during January 2011 (P1), Augst 2011 (P2), April 2012 (P3) and August 2012 (P4). We recorded the duration (days) of the phenological stages, pruning (P), woolly bud (W), budburst (B), inflorescence development (ID), flowering (F), ripening (R) and harvest (H). We analysed the floral biology, the sexual system and the breeding system. We measured the growing degree days (GDD) required to reach the subperiods P-B, B-F and F-H. The periods P1, P2, P3 and P4 lasted for 116, 125, 117 and 130 days, respectively. The number of days of harvest were similar in the same dry (P1 and P3) and rainy (P2 and P4) periods. All the periods that we recorded were shorter than those observed in other regions of Brazil, which may be attributable to the mean temperature and carbohydrate metabolism. The flowers are green, hermaphroditic, with an odour of mignonette, low pollen viability and autogamous. The base temperature of 10 degrees C was considered the most adequate for the subperiods as has been documented for other grape varieties in Brazil. Thus, temperature was also the most adequate for the cycles, presenting a smaller standard deviation (0.119, 0.147, 0.156 and 0.153 to P1, P2, P3 and P4, respectively) when compared to a base temperature of 12 degrees C (0.122, 0.158, 0.165 and 0.160 to P1, P2, P3 and P4, respectively). The higher and the lower observed GDD were 1972.17 and 1870.05, respectively, both above the values recorded in other parts of Brazil for same variety. The phonological results, including knowledge of growing degree days, are important to the planning of cultures at the study site and in other regions that have similar climatic conditions and make it possible to pre determine the harvest. PMID- 27191459 TI - Floristic and structural status of forests in permanent preservation areas of Moju river basin, Amazon region. AB - The goal of this study is to analyze the floristic patterns and the structure of disturbed and undisturbed upland forests, in Permanent Preservation Areas (PPAs) along the Moju river, in the Brazilian state of Para. Trees with a diameter equal to or larger than 10cm at 1.30m from the ground (DBH) >=10cm were analyzed for the upper stratum. For the middle stratum, individuals with DBH between 4.99 and 9.99cm were sampled. Forty-five families and 221 species were found in disturbed forests, and 43 families and 208 species in undisturbed forests. Floristic similarity was high between strata and between forest types, with values above 50%. Similarity was highest between middle strata. The most species-abundant families in undisturbed forests were Fabaceae, Sapotaceae, Chrysobalanaceae and Myrtaceae; the species with the highest density there were Eschweilera grandiflora, Licania sclerophylla and Zygia cauliflora. In disturbed forests, the dominant families were Fabaceae, Sapotaceae, Lecythidaceae and Melastomataceae. The Shannon-Wiener diversity index was 3.21 for undisturbed forests and 2.85 for disturbed forests. Non-metric multidimensional scaling (MDS) analysis did not group the forests by their floristic composition in both upper and middle strata. Overall, the PPA forests along the Moju river, even if disturbed, did not show major floristic changes but substantially change their structural characteristics. PMID- 27191460 TI - First occurrence of Anodontites tenebricosus (Bivalvia: Mycetopodidae) in the Tocantins-Araguaia basin, Brazil. PMID- 27191461 TI - Assessment of benthic macroinvertebrates at Nile tilapia production using artificial substrate samplers. AB - Biomonitoring is a cheap and effective tool for evaluation of water quality, and infer on the balance of aquatic ecosystems. The benthic macroinvertebrates are bioindicators sensitive to environmental changes, and can assist in detecting and preventing impacts such as organic enrichment and imbalance in the food chain. We compared the structure of benthic communities on artificial substrate samplers located in places near and far from net cages for production of Nile tilapia (Oreochromis niloticus). Samplers were manufactured with nylon net, using substrates such as crushed stone, gravel, loofah and cattail leaves. Samples were collected after 30 days of colonization, rinsed and then the specimens were identified and quantified. The following metrics were calculated: richness of Operational Taxonomic Units, Margalef richness, abundance of individuals, Shannon index and evenness index. The macrobenthic community structure was strongly modified according to the proximity of the net cages. Metrics showed significant differences (p < 0.05) between near and distant sites, for both periods (dry and rainy seasons). The position of the samplers significantly affected the structure of macroinvertebrate community, as near sites showed higher values for the community metrics, such as richness and diversity. Near sites presented a larger number of individuals, observed both in the dry and rainy seasons, with a predominance of Chironomidae (Diptera) in the dry season and Tubificidae (Oligochaeta) in the rainy season. PMID- 27191463 TI - Frugivory and seed dispersal of Solanum granuloso-leprosum Dunal (Solanaceae) by birds in deciduous seasonal forest. AB - The goal of this study was to identify which bird species consume Solanum granuloso-leprosum fruits and disperse its seeds. 60 hours of focal observations were carried out between April and May 2006 on the edge of a deciduous forest fragment in the Uruguay River region, Rio Grande do Sul state, Brazil. Ten species were observed in total removing 443 fruits. Saltator similis removed 61.8% of the fruits, followed by Tangara sayaca (17.1%), Pipraeidea bonariensis (11.7%), and T. preciosa (6.8%), while the remaining six species accounted for only 2.5% of the fruits removed. Most fruit removal occurred early in the day or mid-afternoon. The most common feeding behaviors were picking (60.7%), followed by stalling (23%) and hovering (16%). Birds flew more than 10 m from the fruit plant in 62% of the removal events. All bird species observed here may be considered potential dispersers of S. granuloso-leprosum, as they moved the seeds away from the mother plant where strong competition and predation are likely to occur. Results also suggest that S. granuloso-leprosum may be useful in ecological restoration programs. PMID- 27191464 TI - Comparative feeding ecology of four syntopic Hypostomus species in a Brazilian southeastern river. AB - Though their broad distribution in most Brazilian rivers, scarce studies concerning ecological interactions on Hypostomus species are available. This study observes the diet, the trophic interactions and some morphological aspects of four syntopic species of Hypostomus. These fishes were studied at the superior part of the Corumbatai river, at Sao Paulo state, southeastern Brazil. Analyses focused feeding patterns, their amplitude and whether there happens some food items overlap among the species. Fish were caught using cast nets at some points of the river. Species were chosen according to their local abundance and, so there were four main species: H. albopunctatus, H. ancistroides, H. regani and H. strigaticeps. Nine food items were found: sediments, fungi, diatoms, green algae, Tecamoeba, vegetal debris and invertebrates. There were not significant differences for the feeding pattern among the four Hypostomus species. The feeding niche amplitude has been larger for H. albopunctatus influenced by a larger amount of vegetal debris and invertebrates. Elevated niche overlap was found to happen among the species and also for their trophic morphology. Results may suggest that there is a similar pattern in food taken between four species of Hypostomus analyzed since all consume similar environmental resources and have similar anatomical features. However, a different intake insect larvae and plant material in H. albopunctatus diet indicate differences in local and how this species may be exploring their food compared to the others. PMID- 27191462 TI - Protozoa ciliates community structure in urban streams and their environmental use as indicators. AB - The objective of this work was to investigate the patterns of diversity and abundance of ciliates protozoa community in three tropical urban streams and verify which species can be considered bioindicators of water quality. In each stream, three regions (headwater, middle and mouth) were sampled in two years, in the rainy and dry seasons. The abiotic factors (dissolved oxygen, pH, temperature, turbidity, width, depth, flow and conductivity) and biotic factors (total coliforms, bacterioplankton, chlorophyll and flagellates) were analyzed using appropriate methods and ciliates were identified and counted through specialized literature. We identified 84 species distributed into 24 orders. Peniculida was the most representative order followed by Prorodontida. The RDA scores showed a spatial difference between streams. On the other hand, regarding the temporal variation, there was no separation of the sampled data. The Indval analysis showed ten species indicators, such as Coleps hirtus, Euplotes moebiusi and Tintinidium pusillum. The Cluster analysis per stream versus period showed a greater distinction of the streams in the dry season. On the other hand, a low similarity was observed between sections within the same stream. In summary, the results indicated that the ciliates can be used as important tools as bioindicators in lotic environments affected by different degrees of pollution, due to the fact that they have short life cycle, allowing the detection of impacts on a small time scale, as well as by having direct answers to environmental changes and high sensitivity to contaminants. PMID- 27191465 TI - First record of Dendrocerus carpenteri (Hymenoptera: Megaspilidae) on Aphidius ervi in alfalfa fields in Brazil. PMID- 27191466 TI - Heterogeneity of elemental composition and natural abundance of stables isotopes of C and N in soils and leaves of mangroves at their southernmost West Atlantic range. AB - Mangrove communities were selected in the state of Santa Catarina, Brazil, near their southernmost limit of distribution, to study mineral nutrient relation in soils and plants. Communities included three true mangrove species, Rhizophora mangle, Laguncularia racemosa and Avicennia germinans, and two associated species, the fern Acrostichum danaeifolium, and the grass Spartina densiflora. The sites included communities in the lower Rio Tavares near Florianopolis city, Sonho beach near Palhoca city, and the Santo Antonio lagoon. These sites included a full range of mangroves under humid climate where winter temperatures, instead of salinity, may be the main factor regulating their productive capacity and species composition. Soil salinity was determined by the concentration of soluble Na, and soil C and N were linearly correlated indicating their association in organic matter. Tavares site showed higher specific conductivity, and concentrations of Na and Mg in the soil layer below 40 cm depth, indicating larger influence of marine water. Isotopic signature of C increased with soil depth suggesting that microorganisms decomposing organic matter are releasing 13C depleted CO2. Nitrogen isotopic signature decreased with soil depth, indicating enrichment in 15N possibly as a result of denitrification in the upper soil layers. Mineral elements in leaf tissues showed A. schaueriana with higher concentrations of N, P, Na, K, Cu, Zn, and Na/Ca ratio. Spartina densiflora was characterized by the lowest N and K concentrations, and the highest concentrations of Al and Fe. Rhizophora mangle and L. racemosa had the highest Ca concentrations. Carbon isotopic signatures identified S. densiflora as a C4 plant, and A. schaueriana as the mangrove species occupying comparatively more water stressed microsites than the rest. Leaf nitrogen isotopic signatures were positive, in correspondence with the soil values. The results support the hypothesis that sites sampled were comparatively fertile, because sediment transport through fresh water run-off is predominant in humid coasts, and therefore plants were not limited by nutrient supply, nor particularly stressed by soil salinity. PMID- 27191467 TI - Effects of a small natural barrier on the spatial distribution of the fish assemblage in the Verde River, Upper Parana River Basin,Brazil. AB - Geographical barriers influence species distribution and play an important role in the segregation of fish assemblages. The present study aims to test the influence of a small natural barrier on the spatial distribution of fish species in the Verde River, Upper Parana River Basin, Brazil, considering two biotopes: upstream and downstream of the Branca Waterfall. We observed the highest species richness downstream of the Branca Waterfall, which also had the highest number of exclusive species. Richness, evenness, and abundance varied significantly among biotopes. The composition and structure of the fish assemblage differed between biotopes, which were characterized by different indicator species, mainly downstream of the Branca Waterfall. Physical and chemical variables and geographical distance between sites were not responsible for the differences observed. Hence, the present study shows that small barriers can also be crucial in structuring fish fauna and play a key role in the segregation of fish assemblages. PMID- 27191468 TI - Regression models for estimating leaf area of seedlings and adult individuals of Neotropical rainforest tree species. AB - Individual leaf area (LA) is a key variable in studies of tree ecophysiology because it directly influences light interception, photosynthesis and evapotranspiration of adult trees and seedlings. We analyzed the leaf dimensions (length - L and width - W) of seedlings and adults of seven Neotropical rainforest tree species (Brosimum rubescens, Manilkara maxima, Pouteria caimito, Pouteria torta, Psidium cattleyanum, Symphonia globulifera and Tabebuia stenocalyx) with the objective to test the feasibility of single regression models to estimate LA of both adults and seedlings. In southern Bahia, Brazil, a first set of data was collected between March and October 2012. From the seven species analyzed, only two (P. cattleyanum and T. stenocalyx) had very similar relationships between LW and LA in both ontogenetic stages. For these two species, a second set of data was collected in August 2014, in order to validate the single models encompassing adult and seedlings. Our results show the possibility of development of models for predicting individual leaf area encompassing different ontogenetic stages for tropical tree species. The development of these models was more dependent on the species than the differences in leaf size between seedlings and adults. PMID- 27191469 TI - Antioxidant activity and phenol content of extracts of bark, stems, and young and mature leaves from Blepharocalyx salicifolius (Kunth) O. Berg. AB - Phenolic compounds are a group of plant secondary metabolites known to have a variety of bioactivities, including the ability to function as antioxidants. Because of the side effects of the use of synthetic substances, the search for natural and less toxic compounds has increased significantly. This study was designed to evaluate the antioxidant activity and phenol content of hexane, ethyl acetate, and aqueous extracts of the bark (suber) and stems as well as the young and mature leaves of Blepharocalyx salicifolius. The extracts were obtained by extraction with organic solvents and subsequent fractionation by chromatographic partition coefficient. Preliminary tests for the presence of antioxidants were performed using bioautography in thin-layer chromatography. The antioxidant activity of the extracts was assessed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method, and the phenol content of the extracts was quantified using the Folin-Ciocalteu technique. The results showed that 9 of the 12 extracts evaluated displayed very strong antioxidant activity and three displayed moderate activity. Aqueous extracts of the young leaves and bark and the ethyl acetate extract of the young leaves showed the highest levels of antioxidant activity and total phenolic content (TPC). A correlation was observed between TPC and antioxidant activity index (AAI) with a correlation coefficient (r2) of 0.7999. Thus, the high phenol content of B. salicifolius extracts and its correlation with antioxidant activity provide substrates for further studies. PMID- 27191470 TI - Length-weight relationship of Hoplias aff. malabaricus (Bloch, 1794) in a subtropical wetland. PMID- 27191472 TI - Capturing Heterogeneity in Medical Marijuana Policies: A Taxonomy of Regulatory Regimes Across the United States. AB - BACKGROUND: There is considerable movement in the U.S. to legalize use of cannabis for medicinal purposes. Twenty-three U.S. states and the District of Columbia have laws that decriminalize use of marijuana for medicinal purposes. Most prior studies of state medical marijuana laws and their association with overall marijuana use, adolescent use, crime rates, and alcohol traffic fatalities have used a binary coding of whether the state had a medical marijuana law or not. Mixed results from these studies raise the question of whether this method for measuring policy characteristics is adequate. OBJECTIVES: Our objective was to develop a validated taxonomy of medical marijuana laws that will allow researchers to measure variation in aspects of medical marijuana statutes as well as their overall restrictiveness. METHODS/RESULTS: We used a modified Delphi technique using detailed and validated data about each state's medical marijuana law. Three senior researchers coded elements of the state laws in initiation of use, quantity allowed, regulations around distribution, and overall restrictiveness. We used 2013 data from the U.S. National Survey on Drug Use and Health to assess validity of the taxonomy. Results indicate substantial state level variation in medical marijuana policies. Validation analysis supported the taxonomy's validity for all four dimensions with the largest effect sizes for the quantity allowed in the state's medical marijuana policy. CONCLUSIONS/IMPORTANCE: This analysis demonstrates the potential importance of nondichotomous measurement of medical marijuana laws in studies of their impact. These findings may also be useful to states that are considering medical marijuana laws, to understand the potential impact of characteristics of those laws. PMID- 27191471 TI - Acute Retinal Necrosis Presenting in Developmentally-delayed Patients with Neonatal Encephalitis: A Case Series and Literature Review. AB - We report three cases of patients with developmental-delay from neonatal herpetic encephalitis and/or meningitis who presented years later with acute retinal necrosis due to herpes simplex virus. The diagnosis was delayed in all cases due to the patients' inability to verbalize their ocular complaints and cooperate with eye examinations. This case series documents the clinical course, pathophysiologic mechanism, and treatment of acute retinal necrosis in this patient population. Clinicians should understand the importance of prudent consideration of acute retinal necrosis in patients with a history of neonatal herpetic encephalitis and/or meningitis presenting with a red eye. PMID- 27191473 TI - Prevalence of Nontuberculous Mycobacterial Pulmonary Disease, Germany, 2009-2014. AB - We analyzed routine statutory health insurance claim data to determine prevalence of nontuberculous mycobacterial pulmonary disease in Germany. Documented prevalence rates of this nonnotifiable disease increased from 2.3 to 3.3 cases/100,000 population from 2009 to 2014. Prevalence showed a strong association with advanced age and chronic obstructive pulmonary disease. PMID- 27191475 TI - The Medical Bookshelf. AB - Books received are listed as space permits, and those of particular interest to our readers are reviewed. PMID- 27191474 TI - Interprofessional practice in healthcare: Experiences of a faculty learning community. AB - Healthcare reform has had its impact on many health professionals as well as clinical settings, particularly with the enactment of the Affordable Care Act. In healthcare settings, healthcare teams are challenged with new systems of care and changing philosophies of management. However, healthcare providers retain a distinctive sense that they cannot always provide care without some form of collaboration. This article presents the results of a pilot study, which measured the effectiveness of a model of practice utilised at a faculty-practitioner operated university community clinic. The purpose of the study was to measure the perceived effectiveness of a practice model, client satisfaction, and students' perceptions of learning. Implications of this pilot study include providing an interprofessional practice model, which can be replicated in any healthcare setting. This study also provides an opportunity to improve student learning in degree programmes where practice is a significant aspect of the learning process. PMID- 27191477 TI - Coping in adolescence. PMID- 27191476 TI - Editor's Mail. AB - The Editor welcomes readers' comments, and selected letters are published each month. Letters must be signed and should be sent to Editor's Mail at the address shown. The journal reserves the right to condense letters if necessary for space. PMID- 27191478 TI - Cues/Tips. PMID- 27191479 TI - Cardiology in the Magic Kingdom. AB - Since his report on last year's meeting of the American College of Cardiology in Dallas was so well received, we asked Dr James M. Barker to attend this year's meeting, held in Anaheim, California, and again give us a primary care physician's perspective.-R.B.H. PMID- 27191482 TI - Apoptosis-Mediated Chemoprevention by Different Ratios of Fish Oil in Experimental Colon Carcinogenesis. AB - Apoptosis plays an important role in prevention of colon cancer. In the present study, different ratios of fish oil and corn oil increased Fas expression in both phases and a decrease in FasL expression only in post initiation phase. Treatment with fish oil activated the intrinsic apoptotic pathway by increasing Bax expression and Cyt c release and decreasing Bcl-2 levels in both phases. This suggests that intrinsic pathway is upregulated by fish oil; however, Fas-FasL activity may be involved in inhibition of reversal of immune surveillance in tumor cells. PMID- 27191484 TI - Irritable bowel syndrome. PMID- 27191483 TI - Use of Unamplified RNA/cDNA-Hybrid Nanopore Sequencing for Rapid Detection and Characterization of RNA Viruses. AB - Nanopore sequencing, a novel genomics technology, has potential applications for routine biosurveillance, clinical diagnosis, and outbreak investigation of virus infections. Using rapid sequencing of unamplified RNA/cDNA hybrids, we identified Venezuelan equine encephalitis virus and Ebola virus in 3 hours from sample receipt to data acquisition, demonstrating a fieldable technique for RNA virus characterization. PMID- 27191485 TI - Transit time. PMID- 27191486 TI - Microbiome: Bacterial broadband. PMID- 27191487 TI - Perspective: An easier diagnosis. PMID- 27191488 TI - Diet: Food for thought. PMID- 27191490 TI - Q&A: Peter Whorwell. PMID- 27191489 TI - Diagnostics: Filling in the missing pieces. PMID- 27191491 TI - Infectious disease: Something in the water. PMID- 27191493 TI - Irritable bowel syndrome: 4 big questions. PMID- 27191492 TI - Drug development: A healthy pipeline. PMID- 27191494 TI - MicroRNA-126-3p suppresses cell proliferation by targeting PIK3R2 in Kaposi's sarcoma cells. AB - Kaposi's sarcoma is a highly vascular tumor of lymphatic endothelial origin. Many deregulated miRNAs, including miR-126-3p, have been identified in Kaposi's sarcoma tissues. miR-126-3p is the most highly endothelial-specific miRNA that regulates vascular integrity and angiogenesis. In this study, we aimed to determine the effect of miR-126-3p on Kaposi's sarcoma cells through transfection of a miRNA mimic and inhibitor. Moreover, we searched the target gene (PIK3R2) of miR-126-3p using bioinformatics software and further verified PIK3R2 using luciferase reporter assays, Real-time quantitative PCR (qRT-PCR) and western blot. The results demonstrated that miR-126-3p inhibited cell proliferation, arrested cell cycle progression, induced cell apoptosis, and inhibited cell invasion of SLK cells. The bioinformatics analysis and luciferase reporter assay revealed that PIK3R2 mRNA is a direct target of miR-126-3p. Moreover, the level of expression of the PIK3R2 gene was downregulated in SLK cells transfected with miR-126-3p siRNAs. Therefore, our data demonstrated that miR-126-3p is a tumor suppressor miRNA that acts by targeting PIK3R2 in Kaposi's sarcoma cells. These findings contribute to our understanding of the molecular mechanisms underlying Kaposi's sarcoma. PMID- 27191496 TI - Mesenchymal stem cells promote pancreatic adenocarcinoma cells invasion by transforming growth factor-beta1 induced epithelial-mesenchymal transition. AB - Mesenchymal stem cells (MSCs) could be ideal delivery vehicles for antitumor biological agents in pancreatic adenocarcinoma (PA). While the role of MSCs in tumor growth is elusive. Inflammation is an important feature of PA. In this study, we reported that MSCs pre-stimulated with the combination of TNF-alpha and IFN-gamma promote PA cells invasion. The invasion of PA cell lines were evaluate by wound healing assay and transwell assay in vitro and liver metastasis in nude mice. We observed MSCs pre-stimulated with the combination of TNF-alpha and IFN gamma promoted PA cells invasion in vitro and in vivo. Consistent with MSCs promoting PA cells invasion, PA cells were found undergo epithelial-mesenchymal transition (EMT). We demonstrated that MSCs pre-stimulated with both of TNF-alpha and IFN-gamma provoked expression transforming growth factor-beta1 (TGF-beta1). MSCs promoting EMT-mediated PA cells invasion could be reversed by short interfering RNA of TGF-beta1. Our results suggest that MSCs could promote PA cells invasion in inflammation microenvironment and should be cautious as delivery vehicles in molecular target therapy. PMID- 27191495 TI - The ratio of STAT1 to STAT3 expression is a determinant of colorectal cancer growth. AB - The role of STAT1 and STAT3 for colorectal carcinoma (CRC) development and progression is controversial. We evaluated 414 CRC patient samples on tissue microarrays for differential expression of STAT1 and STAT3 protein levels and correlated ratios with clinical parameters. Concomitant absence of nuclear STAT1 and STAT3 expression was associated with significantly reduced median survival by >=33 months (p=0.003). To gain insight into underlying mechanisms, we generated four CRC cell lines with STAT3 knockdown. The cell lines harbor different known mutational drivers and were xenografted into SCID mice to analyze the influence of STAT3 on their tumor growth behavior. Experimental downregulation of STAT3 expression had differential, cell-line specific effects on STAT1 expression levels. STAT1 consistently showed nuclear localization irrespective of its tyrosine phosphorylation status. Two characteristic STAT1/3 expression patterns with opposite growth behavior could be distinguished: cell lines with a low STAT1/high STAT3 ratio showed faster tumor growth in xenografts. In contrast, xenografts of cell lines showing high STAT1 and low STAT3 levels grew slower. Importantly, these ratios reflected clinical outcome in CRC patients as well. We conclude that the ratio of STAT1 to STAT3 expression is a key determinant of CRC progression and that STAT1 counteracts pro-tumorigenic STAT3 signaling. Thus, we suggest that the STAT3/STAT1 ratios are better clinical predictors in CRC as compared to STAT3 or STAT1 levels alone. PMID- 27191497 TI - microRNA-374a suppresses colon cancer progression by directly reducing CCND1 to inactivate the PI3K/AKT pathway. AB - microRNA-374a (miR-374a) exhibits oncogenic functions in various tumor types. Here we report that miR-374a suppresses proliferation, invasion, migration and intrahepatic metastasis in colon adenocarcinoma cell lines HCT116 and SW620. Notably, we detected that PI3K/AKT signaling and its downstream cell cycle factors including c-Myc, cyclin D1 (CCND1), CDK4 and epithelial-mesenchymal transition (EMT)-related genes including ZEB1, N-cadherin, Vimentin, Slug, and Snail were all significantly downregulated after miR-374a overexpression. Conversely, cell cycle inhibitors p21 and p27 were upregulated. Expression of E cadherin was only decreased in HCT116, without any obvious differences observed in SW620 cells. Furthermore, luciferase reporter assays confirmed that miR-374a could directly reduce CCND1. Interestingly, when CCND1 was silenced or overexpressed, levels of pPI3K, pAkt as well as cell cycle and EMT genes were respectively downregulated or upregulated. We examined miR-374a levels by in situ hybridization and its correlation with CCND1 expression in CRC tumor tissues. High miR-374a expression with low level of CCND1 was protective factor in CRC. Together these findings indicate that miR-374a inactivates the PI3K/AKT axis by inhibiting CCND1, suppressing of colon cancer progression. PMID- 27191498 TI - Distinct mechanisms contribute to acquired cisplatin resistance of urothelial carcinoma cells. AB - Cisplatin (CisPt) is frequently used in the therapy of urothelial carcinoma (UC). Its therapeutic efficacy is limited by inherent or acquired drug resistance. Here, we comparatively investigated the CisPt-induced response of two different parental urothelial carcinoma cell lines (RT-112, J-82) with that of respective drug resistant variants (RT-112R, J-82R) obtained upon month-long CisPt selection. Parental RT-112 cells were ~2.5 fold more resistant to CisPt than J-82 cells and showed a different expression pattern of CisPt-related resistance factors. CisPt resistant RT-112R and J-82R variants revealed a 2-3-fold increased CisPt resistance as compared to their corresponding parental counterparts. Acquired CisPt resistance was accompanied by morphological alterations resembling epithelial mesenchymal transition (EMT). RT-112R cells revealed lower apoptotic frequency and more pronounced G2/M arrest following CisPt exposure than RT-112 cells, whereas no differences in death induction were observed between J-82 and J 82R cells. CisPt resistant J-82R cells however were characterized by a reduced formation of CisPt-induced DNA damage and related DNA damage response (DDR) as compared to J-82 cells. Such difference was not observed between RT-112R and RT 112 cells. J-82R cells showed an enhanced sensitivity to pharmacological inhibition of checkpoint kinase 1 (Chk1) and, moreover, could be re-sensitized to CisPt upon Chk1 inhibition. Based on the data we suggest that mechanisms of acquired CisPt resistance of individual UC cells are substantially different, with apoptosis- and DDR-related mechanisms being of particular relevance. Moreover, the findings indicate that targeting of Chk1 might be useful to overcome acquired CisPt resistance of certain subtypes of UC. PMID- 27191499 TI - Emx2 as a novel tool to suppress glioblastoma. AB - Glioblastoma is a devastating CNS tumour for which no cure is presently available. We wondered if manipulation of Emx2, which normally antagonizes cortico-cerebral astrogenesis by inhibiting proliferation of astrocyte progenitors, may be employed to counteract it. We found that Emx2 overexpression induced the collapse of seven out of seven in vitro tested glioblastoma cell lines. Moreover, it suppressed four out of four of these lines in vivo. As proven by dedicated rescue assays, the antioncogenic activity of Emx2 originated from its impact on at least six metabolic nodes, which accounts for the robustness of its effect. Finally, in two out of two tested lines, the tumor culture collapse was also achieved when Emx2 was driven by a neural stem cell-specific promoter, likely active within tumor-initiating cells. All that points to Emx2 as a novel, promising tool for therapy of glioblastoma and prevention of its recurrencies. PMID- 27191500 TI - Functional TRAIL receptors in monocytes and tumor-associated macrophages: A possible targeting pathway in the tumor microenvironment. AB - Despite the accepted dogma that TRAIL kills only tumor cells and spares normal ones, we show in this study that mononuclear phagocytes are susceptible to recombinant TRAIL via caspase-dependent apoptosis. Human resting monocytes and in vitro-differentiated macrophages expressed substantial levels of the functional TRAIL receptors (TRAIL-R1 and TRAIL-R2), while neutrophils and lymphocytes mostly expressed the non-signaling decoy receptor (TRAIL-R3). Accordingly, exclusively monocytes and macrophages activated caspase-8 and underwent apoptosis upon recombinant TRAIL treatment. TRAIL-Rs were up-regulated by anti-inflammatory agents (IL-10, glucocorticoids) and by natural compounds (Apigenin, Quercetin, Palmitate) and their treatment resulted in increased TRAIL-induced apoptosis. In mice, the only signaling TRAIL-R (DR5) was preferentially expressed by blood monocytes rather than neutrophils or lymphocytes. In both mice and humans, Tumor Associated Macrophages (TAM) expressed functional TRAIL-R, while resident macrophages in normal tissues did not. As a proof of principle, we treated mice bearing a murine TRAIL-resistant fibrosarcoma with recombinant TRAIL. We observed significant decrease of circulating monocytes and infiltrating TAM, as well as reduced tumor growth and lower metastasis formation. Overall, these findings demonstrate that human and murine monocytes/macrophages are, among leukocytes, uniquely susceptible to TRAIL-mediated killing. This differential susceptibility to TRAIL could be exploited to selectively target macrophages in tumors. PMID- 27191501 TI - De novo HAPLN1 expression hallmarks Wnt-induced stem cell and fibrogenic networks leading to aggressive human hepatocellular carcinomas. AB - About 20% hepatocellular carcinomas (HCCs) display wild-type beta-catenin, enhanced Wnt signaling, hepatocyte dedifferentiation and bad outcome, suggesting a specific impact of Wnt signals on HCC stem/progenitor cells. To study Wnt specific molecular pathways, cell fates and clinical outcome, we fine-tuned Wnt/beta-catenin signaling in liver progenitor cells, using the prototypical Wnt ligand Wnt3a. Cell biology assays and transcriptomic profiling were performed in HepaRG hepatic progenitors exposed to Wnt3a after beta-catenin knockdown or Wnt inhibition with FZD8_CRD. Gene expression network, molecular pathology and survival analyses were performed on HCCs and matching non-tumor livers from 70 patients by real-time PCR and tissue micro-array-based immunohistochemistry. Wnt3a reprogrammed liver progenitors to replicating fibrogenic myofibroblast-like cells displaying stem and invasive features. Invasion was inhibited by 30 nM FZD7 and FZD8 CRDs. Translation of these data to human HCCs revealed two tight gene networks associating cell surface Wnt signaling, stem/progenitor markers and mesenchymal commitment. Both networks were linked by Hyaluronan And Proteoglycan Link Protein 1 (HAPLN1), that appeared de novo in aggressive HCCs expressing cytoplasmic beta-catenin and stem cell markers. HAPLN1 was independently associated with bad overall and disease-free outcome. In vitro, HAPLN1 was expressed de novo in EPCAM-/NCAM+ mesoderm-committed progenitors, upon spontaneous epithelial-mesenchymal transition and de-differentiation of hepatocyte-like cells to liver progenitors. In these cells, HAPLN1 knockdown downregulated key markers of mesenchymal cells, such as Snail, LGR5, collagen IV and alpha-SMA. In conclusion, HAPLN1 reflects a signaling network leading to stemness, mesenchymal commitment and HCC progression. PMID- 27191502 TI - NRAS and EPHB6 mutation rates differ in metastatic melanomas of patients in the North Island versus South Island of New Zealand. AB - Melanoma, the most aggressive skin cancer type, is responsible for 75% of skin cancer related deaths worldwide. Given that New Zealand (NZ) has the world's highest melanoma incidence, we sought to determine the frequency of mutations in NZ melanomas in recurrently mutated genes. NZ melanomas were from localities distributed between North (35 degrees S-42 degrees S) and South Islands (41 degrees S-47 degrees S). A total of 529 melanomas were analyzed for BRAF exon 15 mutations by Sanger sequencing, and also by Sequenom MelaCarta MassARRAY. While, a relatively low incidence of BRAFV600E mutations (23.4%) was observed overall in NZ melanomas, the incidence of NRAS mutations in South Island melanomas was high compared to North Island melanomas (38.3% vs. 21.9%, P=0.0005), and to The Cancer Genome Atlas database (TCGA) (38.3% vs. 22%, P=0.0004). In contrast, the incidence of EPHB6G404S mutations was 0% in South Island melanomas, and was 7.8% in North Island (P=0.0002). Overall, these data suggest that melanomas from geographically different regions in NZ have markedly different mutation frequencies, in particular in the NRAS and EPHB6 genes, when compared to TCGA or other populations. These data have implications for the causation and treatment of malignant melanoma in NZ. PMID- 27191507 TI - Abstracts Of The Meeting On Obesity Organized By The Contact Groups " Hormones " and " Nutrition " of Frsm/Fwgo On February 23, 1985 In Brussels Effect Of Growth Hormone Releasing Factor (Grf) On Plasma Growth Hormone (Gh) And Prolactin (Prl) Levels In Obese Children. PMID- 27191503 TI - The prognostic role of RANK SNP rs34945627 in breast cancer patients with bone metastases. AB - Receptor activator of NF-kB (RANK) pathway regulates bone remodeling and is involved in breast cancer (BC) progression. Genetic polymorphisms affecting RANK ligand (RANKL) and osteoprotegerin (OPG) have been previously associated with BC risk and bone metastasis (BM)-free survival, respectively. In this study we conducted a retrospective analysis of the association of five missense RANK SNPs with clinical characteristics and outcomes in BC patients with BM. SNP rs34945627 had an allelic frequency of 12.5% in BC patients, compared to 1.2% in the control group (P = 0.005). SNP rs34945627 was not associated with any clinicopathological characteristics, but patients presenting SNP rs34945627 had decreased disease free survival (DFS) (log-rank P = 0.039, adjusted HR 2.29, 95% CI 1.04-5.08, P = 0.041), and overall survival (OS) (log-rank P = 0.019, adjusted HR 4.32, 95% CI 1.55-12.04, P = 0.005). No differences were observed regarding bone disease-free survival (log-rank P = 0.190, adjusted HR 1.68, 95% CI 0.78-3.66, P = 0.187), time to first skeletal-related event (log-rank P = 0.753, adjusted HR 1.28, 95% CI 1.42-3.84; P = 0.665), or time to bone progression (log-rank P = 0.618, adjusted HR 0.511, 95% CI 0.17-1.51; P = 0.233). Our analysis shows that RANK SNP rs34945627 has a high allelic frequency in patients with BC and BM, and is associated with decreased DFS and OS. PMID- 27191504 TI - Structures of paraoxon-inhibited human acetylcholinesterase reveal perturbations of the acyl loop and the dimer interface. AB - Irreversible inhibition of the essential nervous system enzyme acetylcholinesterase by organophosphate nerve agents and pesticides may quickly lead to death. Oxime reactivators currently used as antidotes are generally less effective against pesticide exposure than nerve agent exposure, and pesticide exposure constitutes the majority of cases of organophosphate poisoning in the world. The current lack of published structural data specific to human acetylcholinesterase organophosphate-inhibited and oxime-bound states hinders development of effective medical treatments. We have solved structures of human acetylcholinesterase in different states in complex with the organophosphate insecticide, paraoxon, and oximes. Reaction with paraoxon results in a highly perturbed acyl loop that causes a narrowing of the gorge in the peripheral site that may impede entry of reactivators. This appears characteristic of acetylcholinesterase inhibition by organophosphate insecticides but not nerve agents. Additional changes seen at the dimer interface are novel and provide further examples of the disruptive effect of paraoxon. Ternary structures of paraoxon-inhibited human acetylcholinesterase in complex with the oximes HI6 and 2-PAM reveals relatively poor positioning for reactivation. This study provides a structural foundation for improved reactivator design for the treatment of organophosphate intoxication. Proteins 2016; 84:1246-1256. (c) 2016 Wiley Periodicals, Inc. PMID- 27191510 TI - Arabian, Asian, western: a cross-cultural comparison of aircraft accidents from human factor perspectives. AB - INTRODUCTION: Rates of aviation accident differ in different regions; and national culture has been implicated as a factor. This invites a discussion about the role of national culture in aviation accidents. This study makes a cross cultural comparison between Oman, Taiwan and the USA. METHOD: A cross-cultural comparison was acquired using data from three studies, including this study, by applying the Human Factors Analysis and Classification System (HFACS) framework. The Taiwan study presented 523 mishaps with 1762 occurrences of human error obtained from the Republic of China Air Force. The study from the USA carried out for commercial aviation had 119 accidents with 245 instances of human error. This study carried out in Oman had a total of 40 aircraft accidents with 129 incidences. RESULTS: Variations were found between Oman, Taiwan and the USA at the levels of organisational influence and unsafe supervision. Seven HFACS categories showed significant differences between the three countries (p < 0.05). CONCLUSION: Although not given much consideration, national culture can have an impact on aviation safety. This study revealed that national culture plays a role in aircraft accidents related to human factors that cannot be disregarded. PMID- 27191509 TI - Inhibition of clinical pathogenic herpes simplex virus 1 strains with enzymatically created siRNA pools. AB - Herpes simplex virus (HSV) is a common human pathogen causing severe diseases such as encephalitis, keratitis, and neonatal herpes. There is no vaccine against HSV and the current antiviral chemotherapy fails to treat certain forms of the disease. Here, we evaluated the antiviral activity of enzymatically created small interfering (si)RNA pools against various pathogenic HSV strains as potential candidates for antiviral therapies. Pools of siRNA targeting 0.5-0.8 kbp of essential HSV genes UL54, UL29, or UL27 were enzymatically synthesized. Efficacy of inhibition of each siRNA pool was evaluated against multiple clinical isolates and laboratory wild type HSV-1 strains using three cell lines representing host tissues that support HSV-1 replication: epithelial, ocular, and cells that originated from the nervous system. The siRNA pools targeting UL54, UL29, and UL27, as well as their equimolar mixture, inhibited HSV replication, with the pool targeting UL29 having the most prominent antiviral effect. In contrast, the non-specific control siRNA pool did not have such an effect. Moreover, the UL29 pool elicited only a minimal innate immune response in the HSV-infected cells, thus evidencing the safety of its potential clinical use. These results are promising for the development of a topical RNA interference approach for clinical treatment of HSV infection. J. Med. Virol. 88:2196-2205, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27191511 TI - A review of polychlorinated biphenyls (PCBs) pollution in indoor air environment. AB - Polychlorinated biphenyls (PCBs) were widely used in industrial production due to the unique physical and chemical properties. As a kind of persistent organic pollutants, the PCBs would lead to environment pollution and cause serious problems for human health. Thus, they have been banned since the 1980s due to the environment pollution in the past years. Indoor air is the most direct and important environment medium to human beings; thus, the PCBs pollution research in indoor air is important for the protection of human health. This paper introduces the industrial application and potential harm of PCBs, summarizes the sampling, extracting, and analytical methods of environment monitoring, and compares the indoor air levels of urban areas with those of industrial areas in different countries according to various reports. This paper can provide a basic summary for PCBs pollution control in the indoor air environment. IMPLICATIONS: The review of PCBs pollution in indoor air in China is still limited. In this paper, we introduce the industrial application and potential harm of PCBs, summarize the sampling, extracting, and analytical methods of environment monitoring, and compare the indoor air levels of urban areas with industrial areas in different countries according to various reports. PMID- 27191513 TI - Automated Measurement of Cobblestone Morphology for Characterizing Stem Cell Derived Retinal Pigment Epithelial Cell Cultures. AB - PURPOSE: Assessing the morphologic properties of cells in microscopy images is an important task to evaluate cell health, identity, and purity. Typically, subjective visual assessments are accomplished by an experienced researcher. This subjective human step makes transfer of the evaluation process from the laboratory to the cell manufacturing facility difficult and time consuming. METHODS: Automated image analysis can provide rapid, objective measurements of cultured cells, greatly aiding manufacturing, regulatory, and research goals. Automated algorithms for classifying images based on appearance characteristics typically either extract features from the image and use those features for classification or use the images directly as input to the classification algorithm. In this study we have developed both feature and nonfeature extraction methods for automatically measuring "cobblestone" structure in human retinal pigment epithelial (RPE) cell cultures. RESULTS: A new approach using image compression combined with a Kolmogorov complexity-based distance metric enables robust classification of microscopy images of RPE cell cultures. The automated measurements corroborate determinations made by experienced cell biologists. We have also developed an approach for using steerable wavelet filters for extracting features to characterize the individual cellular junctions. CONCLUSIONS: Two image analysis techniques enable robust and accurate characterization of the cobblestone morphology that is indicative of viable RPE cultures for therapeutic applications. PMID- 27191514 TI - Enzymatic modification by point mutation and functional analysis of an omega-6 fatty acid desaturase from Arctic Chlamydomonas sp. AB - Arctic Chlamydomonas sp. is a dominant microalgal strain in cold or frozen freshwater in the Arctic region. The full-length open reading frame of the omega 6 fatty acid desaturase gene (AChFAD6) was obtained from the transcriptomic database of Arctic Chlamydomonas sp. from the KOPRI culture collection of polar micro-organisms. Amino acid sequence analysis indicated the presence of three conserved histidine-rich segments as unique characteristics of omega-6 fatty acid desaturases, and three transmembrane regions transported to plastidic membranes by chloroplast transit peptides in the N-terminal region. The AChFAD6 desaturase activity was examined by expressing wild-type and V254A mutant (Mut-AChFAD6) heterologous recombinant proteins. Quantitative gas chromatography indicated that the concentration of linoleic acids in AChFAD6-transformed cells increased more than 3-fold [6.73 +/- 0.13 mg g-1 dry cell weight (DCW)] compared with cells transformed with vector alone. In contrast, transformation with Mut-AChFAD6 increased the concentration of oleic acid to 9.23 +/- 0.18 mg g-1 DCW, indicating a change in enzymatic activity to mimic that of stearoyl-CoA desaturase. These results demonstrate that AChFAD6 of Arctic Chlamydomonas sp. increases membrane fluidity by enhancing denaturation of C18 fatty acids and facilitates production of large quantities of linoleic fatty acids in prokaryotic expression systems. PMID- 27191515 TI - Integration host factor and LuxR synergistically bind DNA to coactivate quorum sensing genes in Vibrio harveyi. AB - The cell-cell signaling process called quorum sensing allows bacteria to control behaviors in response to changes in population density. In Vibrio harveyi, the master quorum-sensing transcription factor LuxR is a member of the TetR family of transcription factors that both activates and represses genes to coordinate group behaviors, including bioluminescence. Here, we show that integration host factor (IHF) is a key coactivator of the luxCDABE bioluminescence genes that is required together with LuxR for precise timing and expression levels of bioluminescence during quorum sensing. IHF binds to multiple sites in the luxCDABE promoter and bends the DNA in vitro. IHF and LuxR synergistically bind luxCDABE promoter DNA at overlapping, essential binding sites that are required for maximal gene expression in vivo. RNA-seq analysis demonstrated that IHF regulates 300 genes in V. harveyi, and among these are a core set of 19 genes that are also directly bound and regulated by LuxR. We validated these global analyses by demonstrating that both IHF and LuxR are required for transcriptional activation of the osmotic stress response genes betIBA-proXWV. These data suggest that IHF plays an integral role in one mechanism of transcriptional activation by the LuxR-type family of quorum-sensing regulators in vibrios. PMID- 27191512 TI - In Vitro and In Vivo Enzyme Activity Screening via RNA-Based Fluorescent Biosensors for S-Adenosyl-l-homocysteine (SAH). AB - High-throughput enzyme activity screens are essential for target characterization and drug development, but few assays employ techniques or reagents that are applicable to both in vitro and live cell settings. Here, we present a class of selective and sensitive fluorescent biosensors for S-adenosyl-l-homocysteine (SAH) that provide a direct "mix and go" activity assay for methyltransferases (MTases), an enzyme class that includes several cancer therapeutic targets. Our riboswitch-based biosensors required an alternate inverted fusion design strategy, but retained full selectivity for SAH over its close structural analogue, the highly abundant methylation cofactor S-adenosyl-l-methionine (SAM). The level of ligand selectivity for these fluorescent biosensors exceeded that of commercial antibodies for SAH and proved critical to cellular applications, as we employed them to measure methylthioadenosine nucleosidase (MTAN) activity in live Escherichia coli. In particular, we were able to monitor in vivo increase of SAH levels upon chemical inhibition of MTAN using flow cytometry, which demonstrates high-throughput, single cell measurement of an enzyme activity associated with the biosynthesis of quorum sensing signal AI-2. Thus, this study presents RNA based fluorescent biosensors as promising molecular reagents for high-throughput enzymatic assays that successfully bridge the gap between in vitro and in vivo applications. PMID- 27191517 TI - [The health care through the critical eyes of the users: a survey]. AB - INTRODUCTION: Hospitalization is a condition, in which the individual ceases his daily normal acti- vities to be taken over by a hospital, in order to solve a health problem. The healthcare profes- sionals have the responsibility to make the event "admission" the least traumatic as possible. In this regard the welcome is a crucial moment - like a "business card" for the structure - and it will mostly define the satisfaction of the hospitalization experience. OBJECTIVE: Aim of this study is to explore the experience of hospitalization of the respondents, to outline the main issues that affect the quality of care provided in two hospitals in Rome and to detect the most common critical situations, in relation to the thematic areas identified. METHOD: Data collected through semi-structured questionnaires and following phenomenological approach focused on the analysis of experiences of respondents to extract the meaning themes with inductive technique of Van Kaam. RESULTS: Thanks to the interviews about the users hospitalization experience, there were outlined four key-elements that affect the quality of care provided and the more obvious critical issues detected; therefore it is highlighted a relational and communicative asymmetry between the heal- thcare provider and the user and also a lack of awareness of healthcare professionals on the impor- tance of the "primacy effect", which is a preliminary element to strengthen the subsequent posi- tive perceptions of hospital care. CONCLUSIONS: In the light of the results, that work can provide interesting insights and guidance to all those who, for various reasons, are active in the health professions in addition to contribu- ting to the improvement of the quality of care in our facilities. PMID- 27191516 TI - [Uniform and ornaments of hands of Healthcare workers: a point prevalence survey in Ausl of Rimini]. AB - INTRODUCTION: The debate about uniform and hand ornament of nurses, technical and supporting staff is focused on two main topics: the risk of infections and the effect on the professional image perceived by patient. AIM: PRIMARY OBJECTIVE: to describe how nurses, technical and supporting staff dress their uniform. SECONDARY OBJECTIVE: to verify the use of ornaments of the hands during routine care. METHODS: The survey was conducted in a sample of 503 operators on 67 working contexts in hospital during 14 days. Study questionnaire was composed by 5 items that described behaviors regarding uniform (item 1-2) and the presence of hand ornaments (item 3-4-5). RESULTS: The 17.3% of observed subjects did not wear the uniform and identification badge appropriately; 16.1% had hand ornaments. DISCUSSION: Despite patient delegates, through advisory committee, pointed out the need to identify the workers through the uniform and badge, our results showed inadequate behaviours. The presence of ornaments that interfere with hands hygiene and increase infection risk is a critical issue that has to be periodically monitored. Future interventions are needed to improve behaviours of healthcare personnel. PMID- 27191518 TI - [Efficacy of educational intervention for patients wearing peripherall inserted central catheter. A pilot study]. AB - BACKGROUND: Peripherally Inserted Central Catheter (PICC) is a central venous catheter suitable for patients who receive chemotherapy in Day Hospital regimen. The patient must be educated to a proper home management of the PICC through targeted education. AIM: To evaluate the effectiveness of a targeted educational intervention through the comparison of: indi- vidual interview, brochure paper, informative video. METHOD: Single-centre randomized controlled clinical trial with a simple three-arm comparative scheme. The study population is represented by all patients undergoing the insertion of PICC at the Oncological Day Hospital and Breast Unit in the observation period between October 2013 and February 2014. The Standard educational session is performed by the nurse positioning the PICC. PICC team consists of two nurses in possession of the first level master in venous access management. Following randomization eligible patients were divided in three groups: group A received Standard educational session; group B received the standard information and the brochure; group C received the stan- dard information and the informative video. The level of the achieved knowledge was investigated by administering targeted questionnaires. RESULTS: A total of 40 patients joined the study: a convenience sample represented by people between the ages of 18 and 75 years, in outpatient care. Statistically significant difference in key areas necessary for the proper management of PICC: when to change the dressing (p=0.001), when to wash the catheter (p=0), how to recognize signs and symptoms of infection (p=0.001), identify at-risk behaviors (p=0.005), when carrying out the inspection of the catheter's insertion site (p=0). CONCLUSIONS: The administration of a multimedial educational tool was found to be superior in efficacy compared to the only Standard educational session to increase patient's knowledges. The video appears to be more effective than the brochure. The obtained results are influenced by the small sample size and by the shortness of the follow up timing; this leads to a low generalizability of the conclusions. PMID- 27191519 TI - [Ricerca storica sul contributo di Cristina Trivulzio di Belgiojoso all'assistenza infermieristica]. AB - The aim of this historical research project is to examine the contribution of Cristina Trivulzio Princess of Belgiojoso to the development of the nursing organisation in Italy. Specifically, the analysis focuses on the period of the Roman Republic, as in 1849 Cristina Trivulzio (Princess of Belgiojoso) was one of the person in charge of the service of caring and rescuing of the injured. For this reason, nineteen volumes were analysed out of the one hundred twenty-nine volumes found in five Italian historical archives. All documentary sources were evaluated accordingly to the Chabod historical research method (1999), while for their critical interpretation a scheme of analysis was created. As a result, five topics clearly emerged from the data collected: organisation, health politics, training, research and nursing. To sum up, this research reveals that the contributions of Cristina Trivulzio are so relevant that she may be counted among the founders of the italian nursing organisation. PMID- 27191520 TI - Towards an integrated model of nursing competence: an overview of the literature reviews and concept analysis. AB - INTRODUCTION: Competence is considered a fundamental element when measuring a nurse's or student's ability to provide nursing care, but there is no consensus on what competence really is. This paper aims to review the existing meanings and models of nursing competence. METHOD: The overview of literature reviews and concept analysis was performed through a search on Pubmed, Cinahl and PsychINFO from January 2005 to September 2014. It included key words, such as: Competence Model; Professional Competence; Nursing Competence; Competency Model; Professional Competency; Nursing Competency. RESULT: A total of 14 papers were found, coming from educational or clinical nursing field. It was possible to identify some common themes: description of competence determinants; confu- sion around the competence concept; lack in competence evaluation; lack when competence have to be operationalized. CONCLUSION: The overview results, enriched by the literature coming out from the organiza- tional studies, build the conceptual basis of an integrated model of nursing competence. More empirical research is needed to test the theoretical assumptions. PMID- 27191522 TI - [Editorial]. PMID- 27191521 TI - Nursing diagnoses and theoretical frameworks in neonatal units: a literature review. AB - AIM: To identify nursing diagnoses and theoretical frameworks used in neonatal units through a literature review. METHOD: Cinahl, Medline and Lilacs, database were used to perform this study. The descriptors used were: "Nursing Diagnosis" AND "Models, Nursing" OR "Nursing Theory" AND "Infant" OR "Newborn". The search was limited to articles published from 2000 to November 2013. Studies were selected only if they were written in English, Spanish, Portuguese and Italian. RESULTS: In the literature review two taxonomies and six major theoretical frameworks were identified. The most frequently detected nursing diagnoses were: activity intolerance, impaired spontaneous ventilation, ineffective breathing pattern, risk for aspiration, delayed growth and development, Ineffective breastfeeding, Ineffective infant feeding pattern, hyperthermia / hypothermia, risk for infection, impaired tissue integrity, Interrupted family processes, risk for impaired parenting, risk for impaired attachment, interrupted family processes. Diagnoses applying to parents' psychosocial sphere were identified, enabling the newborn's integral evaluation, including the family. CONCLUSIONS: Nursing diagnoses provide nurses working in neonatal units the opportunity of an effective management of the care process as well as the availability of the needed data in order to continuously improve a quality-based nursing care. The use of one model or more reference models represents a way to help professional action. PMID- 27191523 TI - Binge-eating disorder: emerging treatments for a new diagnosis. AB - PURPOSE OF REVIEW: This review provides an update on the new Diagnostic and Statistical Manual (DSM) diagnosis of binge-eating disorder (BED) by presenting diagnostic criteria, associated risk factors and co-morbidities, and tools for assessment. An update on the currently available evidence-based treatments for adolescent BED is provided to help with the coordination of treatment planning for identified patients with this condition. RECENT FINDINGS: BED is now officially included in the DSM. Research with youth has begun to show improvement from treatments such as cognitive behavioral therapy, previously shown to be useful in adults. SUMMARY: BED is common and often begins during youth. The availability of diagnostic criteria, along with increasing knowledge about the condition and available treatments, is expected to result in improved identification and management in younger patients. PMID- 27191524 TI - Understanding autoimmunity of vitiligo and alopecia areata. AB - PURPOSE OF REVIEW: Vitiligo and alopecia areata are common, disfiguring skin diseases. Treatment options are limited and include nontargeted approaches, such as corticosteroids, topical calcineurin inhibitors, narrow band ultraviolet B phototherapy, and other immune-modifying agents. The purpose of this article is to review shared, novel mechanisms between vitiligo and alopecia areata, as well as discuss how they inform the development of future targeted treatments. RECENT FINDINGS: Vitiligo and alopecia areata are both autoimmune diseases, and striking similarities in pathogenesis have been identified at the level of both the innate and adaptive immune system. Increased reactive oxygen species and high cellular stress level have been suggested as the initiating trigger of the innate immune system in both diseases, and genome-wide association studies have implicated risk alleles that influence both innate and adaptive immunity. Most importantly, mechanistic studies in mouse models of vitiligo and alopecia areata have specifically implicated an interferon (IFN)gamma-driven immune response, including IFNgamma, IFNgamma-induced chemokines, and cytotoxic CD8 T cells as the main drivers of disease pathogenesis. These recent discoveries may reveal an effective strategy to develop new treatments, and several proof-of-concept clinical studies support this hypothesis. SUMMARY: The identification of IFNgamma driven immune signaling pathways has enabled discoveries of potential new treatments for vitiligo and alopecia areata, and supports initiation of larger clinical trials. PMID- 27191526 TI - Further understanding of the immunopathology of multiple sclerosis: impact on future treatments. AB - INTRODUCTION: The understanding of the immunopathogenesis of multiple sclerosis (MS) has expanded with more research into T-cell subtypes, cytokine contributors, B-cell participation, mitochondrial dysfunction, and more. Treatment options have rapidly expanded with three relatively recent oral therapy alternatives entering the arena. AREAS COVERED: In the following review, we discuss current mechanisms of immune dysregulation in MS, how they relate to current treatments, and the impact these findings will have on the future of therapy. Expert commentary: The efficacy of these medications and understanding their mechanisms of actions validates the immunopathogenic mechanisms thought to underlie MS. Further research has exposed new targets, while new promising therapies have shed light on new aspects into the pathophysiology of MS. PMID- 27191527 TI - Whole-exome sequencing strategy proposed as first-line test: WES for well phenotyped infants leads to high diagnostic yield. PMID- 27191525 TI - Clinical implications of new mechanistic insights into atopic dermatitis. AB - PURPOSE OF REVIEW: The review will examine recent advances in our understanding of atopic dermatitis and how these mechanisms provide a framework for new approaches to the management of this common skin disease. RECENT FINDINGS: The mechanisms by which epithelial skin barrier and immune responses contribute to the complex clinical phenotypes found in atopic dermatitis are being elucidated. Atopic dermatitis often precedes food allergy because reduced skin barrier function allows environmental food allergens to penetrate the skin leading to systemic allergen sensitization. There is increasing evidence that atopic dermatitis is a systemic disease. New treatments are focused on intervention in polarized immune responses leading to allergic diseases. This includes antagonism of IL-4 and IL-13 effects. Prevention strategies involve maintaining normal skin barrier function with emollients to prevent allergens and microbes from penetrating the skin. SUMMARY: Recent work on the pathogenesis of atopic dermatitis has important implications for its clinical management, including the development of effective barrier creams and biologicals targeting specific polarized immune pathways resulting in skin inflammation. PMID- 27191528 TI - Website aims to accelerate gene discovery, diagnosis, treatment: MyGene2.org fosters open sharing among families, researchers, and clinicians. PMID- 27191531 TI - Pediatric Uveitis: Experience in Colombia. AB - PURPOSE: To describe the clinical features of uveitis in children treated at two ophthalmologic centers in Bogota, Colombia, in a 13 year-period. METHODS: Retrospective observational clinical record review of pediatric children with diagnosis of uveitis. RESULTS: In total, 310 children were evaluated, 51.9% were female, mean age of 10.1 years. Posterior uveitis was the most common location (58.7%), of insidious onset (87.4%) and chronic course (78.1%). The most common etiology was infection (58.4%) caused by toxoplasmosis (76.8%). There was a statistically significant difference in visual acuity between anterior (20/68) and intermediate uveitis (20/70), compared with posterior uveitis (20/434) (p<0.05). CONCLUSIONS: This is the first study to report the clinical features of pediatric uveitis in Colombia, where infectious etiologies are the leading cause. It will improve awareness and knowledge of pediatric uveitis in developing countries, and contribute to the development of public health policies of pediatric visual health. Received 12 September 2015; revised 23 February 2016; accepted 25 February 2016; published online 18 May 2016. PMID- 27191533 TI - Self-perceived health status, gender, and work status. AB - This study analyzes the relationship between gender and self-perceived health status in Spanish retirees and housewives from a sample of 1,106 community dwelling older adults. A multivariate linear regression model was used in which self-perceived health status was measured by the EQ-5D visual analogue scale and gender according to work status (retired men and women and housewives). Retired males reported a significantly better health status than housewives. Self perceived health status was closely associated with physical, mental, and functional health and leisure activities. Finally, being a woman with complete dedication to domestic work is associated with a worse state of self-perceived health. PMID- 27191534 TI - Characterization of obstructive sleep apnea-hypopnea syndrome (OSA) population by means of cluster analysis. AB - Obstructive sleep apnea-hypopnea syndrome (OSA) is being identified increasingly as an important health issue. It is typified by repeated episodes of upper airway collapse during sleep leading to occasional hypoxaemia, sleep fragmentation and poor sleep quality. OSA is also being considered as an independent risk factor for hypertension, diabetes and cardiovascular diseases, leading to increased multi-morbidity and mortality. Cluster analysis, a powerful statistical set of techniques, may help in investigating and classifying homogeneous groups of patients with similar OSA characteristics. This study aims to investigate the (possible) different groups of patients in an OSA population, and to analyse the relationships among the main clinical variables in each group to better understand the impact of OSA on patients. Starting from a well-characterized OSA population of 198 subjects afferent to our sleep centre, we identified three different communities of OSA patients. The first has a very severe disease [apnea hypopnea index (AHI) = 65.91 +/- 22.47] and sleep disorder has a strong impact on daily life: a low level of diurnal partial pressure of oxygen (PaO2 ) (77.39 +/- 11.64 mmHg) and a high prevalence of hypertension (64%); the second, with less severe disease (AHI = 28.88 +/- 17.13), in which sleep disorders seem to be less important for diurnal PaO2 and have a minimum impact on comorbidity; and the last with very severe OSA (AHI = 57.26 +/- 15.09) but with a low risk of nocturnal hypoxaemia (T90 = 11.58 +/- 8.54) and less sleepy (Epworth Sleepiness Scale 10.00 +/- 4.77). PMID- 27191535 TI - A Single Gene Cluster for Chalcomycins and Aldgamycins: Genetic Basis for Bifurcation of Their Biosynthesis. AB - Aldgamycins are 16-membered macrolide antibiotics with a rare branched-chain sugar d-aldgarose or decarboxylated d-aldgarose at C-5. In our efforts to clone the gene cluster for aldgamycins from a marine-derived Streptomyces sp. HK-2006-1 capable of producing both aldgamycins and chalcomycins, we found that both are biosynthesized from a single gene cluster. Whole-genome sequencing combined with gene disruption established the entire gene cluster of aldgamycins: nine new genes are incorporated with the previously identified chalcomycin gene cluster. Functional analysis of these genes revealed that almDI/almDII, (encoding alpha/beta subunits of pyruvate dehydrogenase) triggers the biosynthesis of aldgamycins, whereas almCI (encoding an oxidoreductase) initiates chalcomycins biosynthesis. This is the first report that aldgamycins and chalcomycins are derived from a single gene cluster and of the genetic basis for bifurcation in their biosynthesis. PMID- 27191532 TI - In Situ Transfection by Controlled Release of Lipoplexes Using Acoustic Droplet Vaporization. AB - Localized delivery of nucleic acids to target sites (e.g., diseased tissue) is critical for safe and efficacious gene therapy. An ultrasound-based technique termed acoustic droplet vaporization (ADV) has been used to spatiotemporally control the release of therapeutic small molecules and proteins contained within sonosensitive emulsions. Here, ADV is used to control the release of lipoplex containing plasmid DNA encoding an enhanced green fluorescent protein reporter from a sonosensitive emulsion. Focused ultrasound (3.5 MHz, mechanical index (MI) >= 1.5) generates robust release of fluorescein (i.e., surrogate payload) and lipoplex from the emulsion. In situ release of the lipoplex from the emulsion using ADV (MI = 1.5, 30 cycles) yields a 55% release efficiency, resulting in 43% transfection efficiency and 95% viability with C3H/10T1/2 cells. Without exposure to ultrasound, the release and transfection efficiencies are 5% and 7%, respectively, with 99% viability. Lipoplex released by ADV retains its bioactivity while the ADV process does not yield any measureable sonoporative enhancement of transfection. Co-encapsulation of Ficoll PM 400 within the lipoplex-loaded emulsion, and its subsequent release using ADV, yield higher transfection efficiency than the lipoplex alone. The results demonstrate that ADV can have utility in the spatiotemporal control of gene delivery. PMID- 27191537 TI - Safety of antitumour necrosis factor treatments in chronic rheumatic diseases: therapy discontinuations related to side effects. AB - WHAT IS KNOWN AND OBJECTIVE: The appearance of antitumor necrosis factor drugs (ATDs) has been a major advance in the management of these patients. However, due to the immunosuppressive effect of these therapies, side effects that require treatment discontinuations can appear. The purpose of this study was to evaluate the frequency of ATD discontinuation due to adverse drug effects (ADEs) and the influence of different factors such as diagnosis, ATD prescribed and concomitant disease-modifying antirheumatic drugs (DMARDs). METHODS: Observational study from a prospective cohort conducted in a tertiary hospital (1350 beds) in Spain. Data were obtained from the database of the Rheumatology Outpatient Unit of the hospital and patients' clinical files. Included patients had a diagnosis of RA or peripheral or axial SpA (ankylosing spondylitis, psoriatic SpA, non-radiographic SpA, SpA associated with inflammatory bowel disease or reactive arthritis) treated between November 2000 and March 2014 with infliximab (IFX), etanercept (ETN) or adalimumab (ADA). RESULTS AND DISCUSSION: Study cohort included 531 rheumatic patients (282 patients with RA, 53.1%, and 249 patients with SpA, 46.9%). ATDs were discontinued in 62 cases (11.7%) because of ADEs, mainly inmunogenicity and infections (mainly due to infusion reactions, 58.1%, and infections, 19.3%). ATD discontinuation was higher in the group of RA patients compared with SpA (44/282 (15.6%) in RA vs. 18/249 (7.23%) in SpA). The appearance of ADEs that led to drop out was more frequent in patients under IFX therapy (45 (18.6%) with IFX vs. 12 (7.59%) with ETN and 5 (3.81%) with ADA). We observed a significantly increased risk of ADEs when patients received IFX than when ETN or ADA were used (P < 0.001); 444 patients (83.6%) received DMARDs in combination with ATDs. The risk of ATD withdrawal was significantly higher in patients treated with leflunomide as compared to those who do not (OR = 1.984, P < 0.05). WHAT IS NEW AND CONCLUSION: Discontinuation of ATD due to ADEs is relatively frequent and it depends on the diagnosis and ATD administered. The risk of treatment discontinuation is higher in patients diagnosed with RA vs. SpA or treated with IFX (rather than with ETN or ADA). The addition of DMARDs to ATDs increased the frequency of treatment discontinuation, up to three concomitant medications. Leflunomide in combination with an ATD significantly increased the probability of treatment discontinuation due to adverse reactions. PMID- 27191536 TI - Effect of Helicobacter pylori Eradication and ABO Genotype on Gastric Cancer Development. AB - BACKGROUND: Evidence is lacking regarding how Helicobacter pylori infection status, eradication history, and ABO blood type affect the development of gastric cancer (GC) given the multifactorial and distinctive etiology according to cancer location (noncardia vs cardia) and histologic type (intestinal vs diffuse-type). We evaluated the effect of H. pylori infection status incorporated with H. pylori eradication history and ABO genotype on GC development according to cancer location and histologic type. METHODS: A case-control study of 997 patients with noncardia GC (NCGC) and 1147 control subjects was performed using risk analyses with 14 factors including H. pylori infection with eradication history and ABO genotype. As final analyses, multivariable logistic regression models were fitted. Additionally, H. pylori infection status with eradication history was tested for its association with age, atrophic gastritis (AG), and intestinal metaplasia (IM). RESULTS: The ABO genotype with the B allele was associated with a significantly lower risk of NCGC of both histologic types. The reduction in risk for NCGC by adding the B allele was more prominent in diffuse-type than that in the intestinal-type. H. pylori infection with eradication history was associated with a significantly lower risk of NCGC of both histologic types, compared with those without eradication history (odds ratio (OR), 0.22; 95% confidence interval (CI), 0.14-0.34) approaching that of uninfected subjects. Past infection status without an eradication history was associated with older age, AG, and IM. CONCLUSIONS: H. pylori eradication and the B allele decreased the risks of the intestinal and diffuse-types of NCGC. H. pylori eradication revealed a strong association against developing NCGC. Therefore, it should be considered as a primary measure in NCGC prevention. PMID- 27191539 TI - Dipeptidyl peptidase-IV inhibitors induced bullous pemphigoid: a case report and analysis of cases reported in the European pharmacovigilance database. AB - WHAT IS KNOWN AND OBJECTIVE: Bullous pemphigoid has been reported in association with gliptins. We describe a case, review the literature and analyse all cases of bullous pemphigoid recorded in the European pharmacovigilance database, EudraVigilance. CASE SUMMARY: A 74-year-old woman, treated with vildagliptin/metformin for 12 months, developed bullous pemphigoid, confirmed by skin biopsy. The symptoms resolved within 7 months after vildagliptin/metformin withdrawal. WHAT IS NEW AND CONCLUSION: A search in EudraVigilance showed a disproportionality for bullous pemphigoid and gliptins, except alogliptin. These findings extend the evidence associating gliptins with this potentially serious disease. PMID- 27191538 TI - Population pharmacokinetics of tacrolimus in Thai kidney transplant patients: comparison with similar data from other populations. AB - WHAT IS KNOWN AND OBJECTIVE: Tacrolimus, the most widely used calcineurin inhibitor in kidney transplantation, has a narrow therapeutic window with high interindividual variability in its pharmacokinetics. Clinically feasible models that combine important factors may help guide individual tacrolimus dosage adjustment in kidney transplant patients. The purpose of this study was to develop a population pharmacokinetic model and investigate the influence of clinical factors on the pharmacokinetics of tacrolimus in adult Thai kidney transplant patients from routine data monitoring. METHODS: A total of 1183 whole blood concentrations from 96 patients were characterized using nonlinear mixed effects modelling. Clinical factors tested for influence on pharmacokinetic parameters were weight, haemoglobin, duration of tacrolimus therapy, prednisolone dose, serum albumin and estimated glomerular filtration rate. RESULTS AND DISCUSSION: A one-compartment model with first-order absorption best described the data. The population estimate of tacrolimus apparent clearance (CL/F) and apparent volume of distribution (V/F) in the final population model was 21.5 L/h (95% CI; 18.38, 24.34) and 333 L (95% CI; 222.66, 484.35), respectively. CL/F increased with decreasing haemoglobin levels and decreased with increasing duration of tacrolimus therapy (both P < 0.001). The population pharmacokinetic equation that predicted CL/F of tacrolimus was CL/F = 21.5 * exp((-0.05 () (HB) ( - 11.8))) * (DOT/125)(-0.06) , where CL/F was tacrolimus apparent oral clearance (L/h), HB was haemoglobin levels (g/dL), and DOT was duration of tacrolimus therapy (days). No covariates significantly influenced V/F. WHAT IS NEW AND CONCLUSION: The first population pharmacokinetic model of tacrolimus in Thai adult kidney transplant patients was developed and validated. Haemoglobin and duration of tacrolimus therapy could partly explain the interindividual variability in the apparent clearance of tacrolimus. This manuscript also provides a summary review of previously reported population pharmacokinetic models of twice daily tacrolimus in adult kidney transplant recipients. PMID- 27191540 TI - Diabetes literacy and informal social support: a qualitative study of patients at a diabetes centre. AB - AIMS AND OBJECTIVES: To explore the resources that patients diagnosed with type 2 diabetes drew upon to manage the disease in their daily lives. BACKGROUND: Type 2 diabetes is a disease affecting Australian adults at a rate described as an 'epidemic'. Treatment usually focuses on patient self-management, which may require daily blood sugar monitoring, oral medications or injectable therapies, and regulating diet and exercise. Health research studies of patient self management, including those involving type 2 diabetes, have focused largely on individual-centred definitions, though a number of studies, in particular qualitative studies, have indicated the positive role of social relationships and informal social networks. DESIGN: Exploratory, qualitative. METHODS: The project focused on 26 patients attending a diabetes centre for clinical consultations with centre staff including doctors, diabetes educators, podiatrists and dietitians. The consultations were observed and audio recorded, followed by semi structured, audio-recorded interviews with the patients and separate interviews with the consulting professional staff. RESULTS: Overwhelmingly the patients drew on informal social networks of support to manage the disease. Spouses were significant, sometimes presenting with the patient as a 'team' approach to managing the disease. Sons and daughters also played a significant support role, especially interpreting during consultations and explaining health information. In some cases neighbours and also local community organisations provided informal support. Only two patients claimed not to use informal social support. CONCLUSIONS: Informal social support in patients' self-management of type 2 diabetes was found to be an important factor to be considered by clinicians. The study suggested the need for a more deliberate or pro-active policy to involve patients' family and other informal social networks in treatment programs. RELEVANCE TO CLINICAL PRACTICE: Clinicians may need document and incorporate informal social support in the development and implementation of patient management plans. PMID- 27191541 TI - Death by a thousand cuts: the slow demise of chemotherapy. PMID- 27191542 TI - The uncovering and characterization of a CCKoma syndrome in enteropancreatic neuroendocrine tumor patients. AB - OBJECTIVE: Neuroendocrine tumors in the pancreas and the gastrointestinal tract may secrete hormones which cause specific syndromes. Well-known examples are gastrinomas, glucagonomas, and insulinomas. Cholecystokinin-producing tumors (CCKomas) have been induced experimentally in rats, but a CCKoma syndrome in man has remained unknown until now. MATERIAL AND METHODS: Using a panel of immunoassays for CCK peptides and proCCK as well as for chromogranin A, we have examined plasma samples from 284 fasting patients with gastroenteropancreatic neuroendocrine tumors. In hyperCCKemic samples, plasma CCK was further characterized by chromatography. RESULTS: One of the patients displayed gross hyperCCKemia. She was a 58-year old woman with a pancreatic endocrine tumor, liver metastases, 500-1000-fold elevated basal CCK concentration in plasma, diarrhea, severe weight loss, recurrent peptic ulcer and bilestone attacks from a contracted gallbladder. The CCK concentrations in plasma were not affected by resection of the pancreatic tumor, but decreased to normal after hemihepatectomy with removal of the metastases. CONCLUSION: A CCKoma syndrome with severe hypersecretion of CCK exists in man. The duodenal ulcer disease and diarrhea with permanently low gastrin in plasma suggest that CCKomas may mimic gastrinoma-like symptoms, because CCK peptides are full agonists of the gastrin/CCK-B receptor. PMID- 27191543 TI - Ecologic Study of Meningococcal B Vaccine and Neisseria gonorrhoeae Infection, Norway. PMID- 27191544 TI - The rise and fall of the CD28 superagonist TGN1412 and its return as TAB08: a personal account. AB - Two decades ago, we discovered 'superagonistic' monoclonal antibodies specific for the CD28 molecule which are able to polyclonally activate T cells, in particular regulatory T cells, and are therapeutically active in many rodent models of autoimmunity, inflammation, transplantation, and tissue repair. A phase I trial of the human CD28 superagonist TGN1412 failed in 2006 due to an unexpected cytokine release syndrome, but after it became clear that dose reduction allows to preferentially address regulatory T cells also in humans, clinical development was resumed under the name TAB08. Here, I recount the story of CD28 superagonist development from a personal perspective with an emphasis on the dramatic events during and after the 2006 phase I trial, the reasons for the failure of preclinical research to warn of the impending cytokine storm, and on the research which allowed resumption of clinical development. PMID- 27191545 TI - Trends in National Institutes of Health Funding of Principal Investigators in Dermatology Research by Academic Degree and Sex. AB - IMPORTANCE: National Institutes of Health (NIH) grants are becoming increasingly competitive in the academic research arena. Identifying NIH funding disparities is an important step in improving academic diversity. OBJECTIVE: To examine recent NIH funding trends in dermatology. DESIGN, SETTING, AND PARTICIPANTS: Retrospective study with linear regression analysis and repeated-measures analysis of variance of all NIH grants awarded to departments of dermatology from fiscal year 2009 to 2014. Funding data were exported from the NIH Research Portfolio Online Reporting Tools Expenditures and Results. Publication data were drawn from Scopus. All NIH-funded principal investigators in dermatology were categorized by their academic degree and sex. MAIN OUTCOMES AND MEASURES: The NIH funding trends were compared by investigator degree (MD, PhD, or MD/PhD) and sex. RESULTS: A total of 1292 NIH-funded grants were awarded to dermatology research from fiscal year 2009 through 2014. Adjusted NIH funding for dermatologic research diminished by 4.6% from $67.3 million in 2009 to $64.2 million in 2014, with a nadir of $58.6 million in 2013. Funding for the NIH's Research Project Grant Program (R01) decreased by 21.0% from $43.9 million to $34.7 million during this period. The dollar amount of NIH funding significantly trended down for investigators with an MD degree by $1.35 million per year from $23.6 million in 2009 to $18.4 million in 2014 (P = .02) while there was no significant change in NIH funding for MD/PhD (from $17.6 million in 2009 to $19.8 million in 2014; P = .44) and PhD investigators (from $26.1 million in 2009 to $25.9 million in 2014; P = .74). Similarly, the total dollar amount of R01 grants awarded to principal investigators with only an MD degree trended down by $1.4 million per year from $13.2 million in 2009 to $6.0 million in 2014 (P < .001). The number of female investigators with NIH grants in dermatology trended down significantly compared with the trend of their male counterparts (from 49 women in 2009 to 43 women in 2014 vs from 84 men in 2009 to 97 men in 2014; P = .04). CONCLUSIONS AND RELEVANCE: There is a downward trend in NIH funding for female and MD-only dermatology investigators. Departmental support and junior faculty mentorship for women and MD investigators is crucial for maintaining their presence in NIH funded dermatology research. PMID- 27191546 TI - Examining the complexities of affective experience will enhance our understanding of pain and inform new interventions designed to bolster resilience. PMID- 27191547 TI - Treatment Options for Veterans With Posttraumatic Stress Disorder. PMID- 27191549 TI - Effects of market, e-marketing, and technology orientations on innovativeness and performance in Turkish health organizations. AB - This article investigates the effects of strategic orientation on innovativeness and performance in health organizations in Turkey. We test hypotheses that market, e-marketing, and technology orientations positively affect innovativeness and performance. Market and technology orientations are found not have a significant effect on performance, but e-marketing orientation and innovativeness have a significant and positive effect. We also investigate indirect effects on innovativeness and performance. The analyses of direct and indirect effects are an important contribution to understanding relationships among research variables. PMID- 27191548 TI - Methionine-Restricted Diet Increases miRNAs That Can Target RUNX2 Expression and Alters Bone Structure in Young Mice. AB - Dietary methionine restriction (MR) increases longevity and improves healthspan in rodent models. Young male C57BL/6J mice were placed on MR to assess effects on bone structure and formation. Mice were fed diets containing 0.86% or 0.12% methionine for 5 weeks. Fasting blood plasma was analyzed for metabolic and bone related biomarkers. Tibiae were analyzed by histomorphometry, while femurs were analyzed by micro-CT and biomechanically using 4-point bending. MR mice had reduced plasma glucose and insulin, while FGF21 and FGF23 increased. Plasma levels of osteocalcin and osteoprotegrin were unaffected, but sclerostin and procollagen I decreased. MR induced bone marrow fat accretion, antithetical to the reduced fat depots seen throughout the body. Cortical bone showed significant decreases in Bone Tissue Density (BTD). In trabecular bone, mice had decreased BTD, bone surface, trabecula and bone volume, and trabecular thickness.. Biomechanical testing showed that on MR, bones were significantly less stiff and had reduced maximum load and total work, suggesting greater fragility. Reduced expression of RUNX2 occurred in bone marrow of MR mice. These results suggest that MR alters bone remodeling and apposition. In MR mice, miR-31 in plasma and liver, and miR-133a, miR-335-5p, and miR-204 in the bone marrow was elevated. These miRNAs were shown previously to target and regulate Osterix and RUNX2 in bone, which could inhibit osteoblast differentiation and function. Therefore, dietary MR in young animals alters bone structure by increasing miRNAs in bone and liver that can target RUNX2. J. Cell. Biochem. 118: 31-42, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27191550 TI - Removal of nickel(II) from aqueous solution by Vigna unguiculata (cowpea) pods biomass. AB - The potential to remove nickel(II) ions from aqueous solution using a biosorbent prepared from Vigna unguiculata pods (VUPs) was investigated in batch experiments. The batch mode experiments were conducted utilising the independent variables of pH (2 to 8), contact time (5 to 120 min), dosage concentration (0.2 to 1.6 g), nickel(II) concentrations (10 to 80 mg L(-1)) and temperature (20 to 50 degrees C). The biosorption data fitted best to the Freundlich biosorption model with a correlation coefficient (R(2)) of 0.993 and lowest chi-squared value of 31.89. The maximum sorption capacity of the VUP for nickel(II) was 27.70 mg g( 1). Kinetics studies revealed that the biosorption process followed the pseudo second-order model as it had the lowest sum of square error value (0.808) and correlation coefficient close to unity (R(2) = 0.998). The calculated thermodynamic parameters showed that the biosorption process was feasible, spontaneous and endothermic. Consequently, the study demonstrated that VUP biomass could be used as a biosorbent for the removal of nickel(II) from aqueous solution. PMID- 27191552 TI - The activated sludge metabolic characteristics changing sole carbon source from readily biodegradable acetate to toxic phenol. AB - A sequencing batch reactor was used to investigate the effect of carbon sources on the metabolism of activated sludge. Acetate and phenol, with the chemical oxygen demand (COD) of 330-350 mg L(-1), was used as the carbon source in Periods I and II, respectively. Acetate decreased in the initial 120 min with the intracellular storage materials (XSTO), extracellular polymeric substances (EPS), and the soluble microbial products (SMP) accumulating to 131.0 mg L(-1), 347.5 mg L(-1), and 35.5 mg L(-1), respectively. Then, XSTO and EPS decreased to 124.5 mg L(-1) and 340.0 mg L(-1), respectively, in the following 120 min. When acetate was replaced by phenol, it could not be used at the beginning due to its toxicity. The XSTO decreased from 142 mg L(-1) to 54.6 mg L(-1) during the aeration period. The EPS had a significant increase, with the highest value of 618.1 mg L(-1), which then decreased to 245.6 mg L(-1) at 240 min. The phenol was gradually degraded with the acclimation and it can be fully degraded 18 d later. Meanwhile, the usage ratio of the internal carbon source decreased. The effluent SMP in Period II was 1.7 times that in Period I. PMID- 27191551 TI - The investigation of the sludge reduction efficiency and mechanisms in oxic settling-anaerobic (OSA) process. AB - This paper aims to provide a full understanding of the sludge reduction mechanisms in the oxic-settling-anaerobic (OSA) process and presents an evaluation of the sludge reduction efficiencies and sludge characteristics in this process compared to the conventional activated sludge process. Fifty-eight percent reduction in observed yield in the OSA process was achieved compared to the control system at the end of the operational period with no deterioration of effluent quality. The settleability of sludge in the OSA process was also found to be better than that of the control system in terms of sludge volume index. In long-term operation, capillary suction time and specific resistance to filtration values confirmed that the OSA process showed good filterability characteristics. The results of batch experiments showed that higher endogenous respiration in the systems might lead to lower sludge production and that energy uncoupling had only a limited impact on sludge reduction. PMID- 27191553 TI - Mutagenicity, cytotoxicity and phytotoxicity evaluation of biodegraded textile effluent by fungal ligninolytic enzymes. AB - Colored effluents from the textile industry have led to severe environmental pollution, and this has emerged as a global issue. The feasibility of ligninolytic enzymes for the detoxification and degradation of textile wastewater was investigated. Ganoderma lucidum crude ligninolytic enzymes extract (MnP 717.7, LiP 576.3, and Laccase 323.2 IU/mL) was produced using solid-state culture using wheat bran as substrate. The biodegradation treatment efficiency was evaluated on the basis of degradation and detoxification of textile effluents. Standard bioassays were employed for mutagenicity, cytotoxicity and phytotoxicity evaluation before and after biodegradation. The degradation of Masood Textile, Kalash Textile, Khyber Textile and Sitara Textile effluents was achieved up to 87.29%, 80.17%, 77.31% and 69.04%, respectively. The biochemical oxygen demand, chemical oxygen demand, total suspended solids and total organic carbon were improved considerably as a result of biodegradation of textile effluents, which were beyond the permissible limits established by the National Environmental Quality Standards before treatment. The cytotoxicity (Allium cepa, hemolytic, Daphnia magna and brine shrimp), mutagenicity (Ames TA98 and TA100) and phytotoxicity (Triticum aestivum) tests revealed that biodegradation significantly (P < 0.05) detoxifies the toxic agents in wastewater. Results revealed that biodegradation could possibly be used for remediation of textile effluents. However, detoxification monitoring is crucial and should always be used to evaluate the bio-efficiency of a treatment technique. PMID- 27191555 TI - Life cycle assessment comparison of activated sludge, trickling filter, and high rate anaerobic-aerobic digestion (HRAAD). AB - This paper conducts a comparative assessment of the environmental impacts of three methods of treating primary clarifier effluent in wastewater treatment plants (WWTPs) through life cycle assessment methodology. The three technologies, activated sludge (AS), high rate anaerobic-aerobic digestion (HRAAD), and trickling filter (TF), were assessed for treatment of wastewater possessing average values of biochemical oxygen demand and total suspended solids of 90 mg L(-1) and 70 mg L(-1), respectively. The operational requirements to process the municipal wastewater to effluent that meets USEPA regulations have been calculated. The data for the AS system were collected from the East Honolulu WWTP (Hawaii, USA) while data for the HRAAD system were collected from a demonstration scale system at the same plant. The data for the TF system were estimated from published literature. Two different assessment methods have been used in this study: IMPACT 2002+ and TRACI 2. The results show that TF had the smallest environmental impacts and that AS had the largest, while HRAAD was in between the two but with much reduced impacts compared with AS. Additionally, the study shows that lower sludge production is the greatest advantage of HRAAD for reducing environmental impacts compared with AS. PMID- 27191554 TI - Visible light induced photocatalytic degradation of rhodamine B by magnetic bentonite. AB - The photocatalytic activity of magnetic bentonite, Fe3O4 nanoparticles decorated Al-pillared bentonite (Fe3O4/Al-B), for the degradation of rhodamine B (RhB) in the presence of H2O2 under visible light (VL) was evaluated. The effects of different reaction parameters such as catalyst dose, dye concentration and externally added H2O2 were also investigated. The magnetic bentonite showed good photocatalytic activity, magnetic separability and stability for repeated use. More than 95% of 40 mg/L RhB was converted within 3 h under VL with a catalyst dose of 0.5 g/L. Suitable mechanisms have been proposed to account for the photocatalytic activities in the presence and absence of H2O2. The efficiency of H2O2 in VL process was much higher than that of the dark process. Results obtained in the current study may be useful to develop a suitable photocatalyst for photocatalytic remediation of different water contaminants including organic dyes. PMID- 27191556 TI - Breakthrough curves of oil adsorption on novel amorphous carbon thin film. AB - A novel amorphous carbon thin film (ACTF) was prepared by hydrolyzing wood sawdust and delignificating the residue to obtain cellulose mass that was subjected to react with cobalt silicate nanoparticle as a catalyst under the influence of sudden concentrated sulfuric acid addition at 23 degrees C. The novel ACTF was obtained in the form of thin films like graphene sheets having winding surface. The prepared ACTF was characterized by Fourier-transform infrared spectrometer, transmission electron microscope (TEM), and Brunauer Emmett-Teller (BET). The adsorption capacity of ACTF to remove oil from synthetic produced water was evaluated using the incorporation of Thomas and Yoon-Nelson models. The performance study is described through the breakthrough curves concept under relevant operating conditions such as column bed heights (3.8, 5 and 11 mm) and flow rate (0.5, 1 and 1.5 mL.min(-1)). It was found that the oil uptake mechanism is favoring higher bed height. Also, the highest bed capacity of 700 mg oil/g ACTF was achieved at 5 mm bed height, and 0.5 mL.min(-1) flow rate. The results of breakthrough curve for oil adsorption was best described using the Yoon-Nelson model. Finally, the results illustrate that ACTF could be utilized effectively for oil removal from synthetic produced water in a fixed-bed column system. PMID- 27191557 TI - Characterization of char from slow pyrolysis of sewage sludge. AB - The effects of final pyrolysis temperature Tend from 300 oC to 550 oC, heating rates beta of 2 oC/min, 3 oC/min and 5 oC/min, retention time RT from 45 min to 90 min, and the moisture content MC from 0 to 70% on characteristics of the pyrolysis char from sewage sludge were investigated using a tube furnace in this study. The resulting chars were characterized by sorption of nitrogen (surface area and pore volume). Their adsorption characteristics were evaluated via iodine value and methylene blue value. Either the pore structures or adsorption characteristics depend on the pyrolysis processing and moisture content of the sludge precursors. In terms of iodine value and surface area of the char, Tend of 450 oC, RT of 75 min and beta of 3 oC/min proved the optimum combination of pyrolysis parameters. The chars have an undeveloped mesopore and macropore structure and a developed micropore structure. The sodium phenoxide adsorption equilibrium data fit well with the Langmuir model of adsorption, suggesting monolayer coverage of sodium phenoxide molecules at the surface of the char. Its adsorption mechanism is mainly physical in nature, enhanced by chemisorption. PMID- 27191558 TI - A surfactant-free solvothermal synthesis of Cu2O microcrystals and their photocatalytic activity. AB - The Cu2O octahedral microcrystals have been successfully fabricated by a surfactant-free solvothermal approach. The morphology and structure of the as prepared sample were characterized by scanning electron microscopy, X-ray powder diffraction and UV-Vis spectroscopy. It was found that the structure and morphology of Cu2O microcrystals were strongly affected by synthesis time and temperature. Based on the time-dependent experiment, the possible formation mechanism of Cu2O octahedral microcrystals was proposed. The photocatalytic activities of as-prepared Cu2O samples were also evaluated for degradation of methyl orange under visible-light irradiation. The results showed that the Cu2O synthesized at 180 degrees C for 4 h had a better photocatalytic performance due to its high percentage of exposed (111) crystal facet and the lowest band gap energy. PMID- 27191559 TI - Anaerobic digestion of aliphatic polyesters. AB - Anaerobic processes for the treatment of plastic materials waste represent versatile and effective approach in environmental protection and solid waste management. In this work, anaerobic biodegradability of model aliphatic polyesters, poly(L-lactic acid) (PLA), and poly(E-caprolactone) (PCL), in the form of powder and melt-pressed films with varying molar mass, was studied. Biogas production was explored in batch laboratory trials at 55 +/- 1 degrees C under a nitrogen atmosphere. The inoculum used was thermophilic digested sludge (total solids concentration of 2.9%) from operating digesters at the Central Waste Water Treatment Plant in Prague, Czech Republic. Methanogenic biodegradation of PCLs typically yielded from 54 to 60% of the theoretical biogas yield. The biodegradability of PLAs achieved from 56 to 84% of the theoretical value. High biogas yield (up to 677 mL/g TS) with high methane content (more than 60%), comparable with conventionally processed materials, confirmed the potential of polyester samples for anaerobic treatment in the case of their exploitation in agriculture or as a packaging material in the food industry. PMID- 27191560 TI - Poly-(acryl amine-co-dimethyldiallyl ammonium chloride) graft starch flocculant for cleaning-up of wastewater. AB - Graft starch flocculant (GSF) was synthesized by copolymerization of carboxymethylated soluble starch, acryl amine and dimethyldiallyl ammonium chloride using ceric ammonium nitrate (NH4)2Ce(NO3)6 as the polymerization initiator. The morphology was observed by scanning electron microscope, the structure was characterized by Fourier transform infrared spectroscopy and the surface area was measured by the Brunauer-Emmett-Teller method. The experimental results showed that the GSF had huge pore volume, high specific area and proper reaction groups, which could enhance its ability to adsorb heavy metal ions. The adsorption behavior was investigated through batch experiments in simulated Cu(2+)and Pb(2+) ions wastewater, and adsorption characteristics were affected by many factors, such as flocculant concentration, pH of the solution and adsorption time. Finally, the optimal adsorption parameters were gained, with GSF density of 0.024 mg.L(-1), pH of 8 and a reaction time of 30 min. Application experiments adequately demonstrated that the removal ratio of Cu(2+) and Pb(2+) ions for the local wastewater reached about 50% based on the above optimized condition. PMID- 27191561 TI - Application of response surface methodology and artificial neural network: modeling and optimization of Cr(VI) adsorption process using Dowex 1X8 anion exchange resin. AB - We report the adsorption efficiency of Cr(VI) on a strong anionic resin Dowex 1X8. The Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analysis of this adsorbent were investigated. Response surface methodology was applied to evaluate the main effects and interactions among initial pH, initial Cr(VI) concentration, adsorbent dose and temperature. Analysis of variance depicted that resin dose and initial pH were the most significant factors. Desirability function (DF) showed that the maximum Cr(VI) removal of 95.96% was obtained at initial pH 5, initial Cr(VI) concentration of 100 mg/L, resin dose of 2 g and temperature of 283 K. Additionally, a simulated industrial wastewater containing 14.95 mg/L of Cr(VI) was treated successfully by Dowex 1X8 at optimum conditions. Same experimental design was employed to develop the artificial neural network. Both models gave a high correlation coefficient (RRSM(2) = 0.932, RANN(2) = 0.996). PMID- 27191562 TI - Water quality of Danube Delta systems: ecological status and prediction using machine-learning algorithms. AB - Environmental issues have a worldwide impact on water bodies, including the Danube Delta, the largest European wetland. The Water Framework Directive (2000/60/EC) implementation operates toward solving environmental issues from European and national level. As a consequence, the water quality and the biocenosis structure was altered, especially the composition of the macro invertebrate community which is closely related to habitat and substrate heterogeneity. This study aims to assess the ecological status of Southern Branch of the Danube Delta, Saint Gheorghe, using benthic fauna and a computational method as an alternative for monitoring the water quality in real time. The analysis of spatial and temporal variability of unicriterial and multicriterial indices were used to assess the current status of aquatic systems. In addition, chemical status was characterized. Coliform bacteria and several chemical parameters were used to feed machine-learning (ML) algorithms to simulate a real time classification method. Overall, the assessment of the water bodies indicated a moderate ecological status based on the biological quality elements or a good ecological status based on chemical and ML algorithms criteria. PMID- 27191563 TI - Adsorption characteristics of Pb(II) from aqueous solutions onto a natural biosorbent, fallen arborvitae leaves. AB - In this study, the potential of the oriental arborvitae leaves for the adsorption of Pb(II) from aqueous solutions was evaluated. Brunauer-Emmett-Teller analysis showed that the surface area of arborvitae leaves was 29.52 m(2)/g with pore diameter ranging from 2 to 50 nm. X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy showed C-C or C-H, C-O, and O-C=O were the main groups on the arborvitae leaves, which were the main sites for surface complexation. Finally, effects of adsorbent dose, initial pH, contact time, and coexisting natural organic matters (humic acid (HA)) on the adsorption of Pb(II) were investigated. The results indicated that the pHZPC (adsorbents with zero point charge at this pH) was 5.3 and the adsorption reached equilibrium in 120 min. Isotherm simulations revealed that the natural arborvitae leaves exhibit effective adsorption for Pb(II) in aqueous solution, giving adsorptive affinity and capacity in an order of 'no HA' > 5 mg/L HA > 10 mg/L HA, and according to the Langmuir models, the maximum adsorptions of Pb(II) were 43.67 mg/g, 38.61 mg/g and 35.97 mg/g, respectively. The results demonstrated that the oriental arborvitae leaves showed high potentials for the adsorption of Pb(II) from aqueous solutions. PMID- 27191565 TI - Biodegradation and decolorization of melanoidin solutions by manganese peroxidase yeasts. AB - The ability of selected manganese peroxidase (MnP) yeast strains, isolated from the mixed liquor of an activated sludge bioreactor treating melanoidins wastewater, was investigated in this work, aiming to examine the degradation potential of melanoidins, in the presence or absence of nutrients. Ten yeast strains were initially isolated from the mixed liquor; four yeast strains (Y1, Y2, Y3 and Y4) were selected for further studies, based on their tolerance towards synthetic melanoidins (SMs) degradation and MnP activity onto solid agar medium. The Y1 strain exhibited almost 98% homology to Candida glabrata yeast, based on 28S rRNA identification studies. During experiments carried out using SM at 30 degrees C, the four isolated yeast cultures showed a noticeable organic matter reduction and decolorization capacity reaching up to 70% within 2-5 days. However, the corresponding yeast cultures grown in glucose peptone yeast extract medium using real melanoidin wastewater at 30 degrees C showed lower organic matter and color removal capacity, reaching about 60% within 2-5 days. Nevertheless, it was found that the removal of real and synthetic melanoidins could be carried out by these strains under non-aseptic conditions, without requiring further addition of nutrients. PMID- 27191564 TI - Simulations of nutrient emissions from a net cage aquaculture system in a Brazilian bay. AB - Hydrodynamics and transport simulations were conducted with the modeling software TELEMAC-2D on Ico-Mandantes bay, a branch of the Itaparica reservoir. The bay has a maximal operational water level amplitude of 5 m and is suffering from eutrophication and algae bloom. Therefore, we investigated low and high water level scenarios with two different high resolution meshes, with the purpose to deeper understand their impact on transport of substances and to improve the watershed management. In particular, nutrient emissions from a hypothetical net cage aquaculture system located in the bay were investigated on half-year cycles. We observed a relevant impact on water quality for a tilapia production of 130 t y(-1); i.e. after 6 months' simulation we obtained around 8 MUgP L(-1) and 6 MUgP L(-1) at the source of emissions, for low and high water scenarios, respectively. PMID- 27191566 TI - Anaerobic treatment of sulfate-containing municipal wastewater with a fluidized bed reactor at 20 degrees C. AB - This study focuses on the anaerobic treatment of sulfate-containing municipal wastewater at 20 degrees C with a fluidized bed reactor. Mean influent chemical oxygen demand (COD) and sulfate concentrations were 481 and 96 mg/l. The response of the COD removal efficiency to increasing organic loading rates (OLR) was investigated. Average total COD removal was 61% at OLR between 2.7 and 13.7 kg COD/(m3.d) and did not distinctly depend on the OLR. To assess the removal efficiency in more detail the COD in- and output mass flows were balanced. The results showed that only 11-12% of the input COD was recovered as gaseous methane. About 12-13% of the input COD remained in the effluent as dissolved methane. Furthermore, a distinct amount of 12-19% of the input COD remained in the reactor as settled sludge and was not further biologically degraded. Due to the reduction by sulfate-reducing bacteria, 13-14% of the input COD was degraded. Further adverse impacts of the influent sulfate on the anaerobic treatment process are discussed as well. PMID- 27191567 TI - Adsorption efficiency of natural materials for low-concentration cesium in solution. AB - In this study, several natural materials were investigated in order to clarify their potential use as cesium (Cs) adsorbents in situ. Four materials--carbonized rice hull, beech sawdust, oak sawdust, and charcoal (Japanese cedar)--which were previously shown to have Cs adsorption capabilities, were examined. Cs adsorption experiments were conducted using different initial Cs and adsorbent concentrations. The physical properties, adsorption isotherms, and adsorption processes were then examined, so as to exploit the Cs adsorption characteristics in the field. Based on these findings, carbonized rice hull and beech sawdust were selected as effective Cs adsorbents. It was found that these materials show continuous and stable Cs adsorption rates for different initial Cs concentrations. The adsorption efficiency of these two adsorption materials in combination was considered, and it was shown that the adsorption isotherms for carbonized rice hull and beech sawdust follow the Freundlich model. Furthermore, the beech sawdust adsorption process exhibited better agreement with the calculated values obtained via the adsorption rate model and the adsorption kinetics model than did the carbonized rice hull adsorption. PMID- 27191568 TI - Effect of carrier fill ratio on biofilm properties and performance of a hybrid fixed-film bioreactor treating coal gasification wastewater for the removal of COD, phenols and ammonia-nitrogen. AB - The purpose of this study was to determine the effect different biofilm carrier filling ratios would have on biofilm morphology and activity and bacterial diversity in a hybrid fixed-film bioreactor treating high strength coal gasification wastewater (CGWW) for the removal of chemical oxygen demand (COD), phenols and ammonia-nitrogen. Results showed that a carrier fill of 70% formed a 'compact' biofilm, a 50% fill formed a 'rippling' biofilm and a 30% fill formed a 'porous' biofilm. The highest microbial activity was obtained with a 50% carrier fill supporting a relatively thin biofilm. The highest level of biofilm bound metals were aluminium, silicon, calcium and iron in the 'compact' biofilm; nitrogen, magnesium, chloride, sodium and potassium in the 'rippling' biofilm, and copper in the 'porous' biofilm. The bioreactor improved the quality of the CGWW by removing 49% and 78% of the COD and phenols, respectively. However, no significant amount of ammonia-nitrogen was removed since nitrification did not take place due to heterotrophic bacteria out-competing autotrophic nitrifying bacteria in the biofilm. The dominant heterotrophic genera identified for all three carrier filling ratios were Thauera, Pseudaminobacter, Pseudomonas and Diaphorobacter. PMID- 27191569 TI - Determining anaerobic degradation kinetics from batch tests. AB - Data obtained from a biomethane potential (BMP) test were used in order to obtain the parameters of a kinetic model of solid wastes anaerobic degradation. The proposed model considers a hydrolysis step with a first order kinetic, a Monod kinetic for the soluble organic substrate degradation and a first order decay of microorganisms. The instantaneous release of methane was assumed. The parameters of the model are determined following a direct search optimization procedure. A 'multiple-shooting' technique was used as a first step of the optimization process. The confidence interval of the parameters was determined by using Monte Carlo simulations. Also, the distribution functions of the parameters were determined. Only the hydrolysis first order constant shows a normal distribution. PMID- 27191570 TI - Analysis and numerical simulation of natural and human-caused low dissolved oxygen in the Minjiang River Estuary. AB - The Minjiang River, a typical tidal channel in Southeast China, plays an important role in the supply of drinking water, flood control and drought relief, farming and navigation, as well as shipping and other functions. Dissolved oxygen (DO), as a basic living condition for aquatic biota, has been deteriorating in the Minjiang River in recent years. In order to understand how the spatial distribution of DO responds to river discharge, nutrient loading and water temperature, a three-dimensional Environmental Fluid Dynamics Code model was used to simulate water age and the distribution of DO in the Minjiang River. The model presented in this paper was used for water resource and water quality simulations under various physical, chemical, and biological scenarios. Sensitivity simulation results indicated that the three factors had a significant impact on the spatial distribution variation of DO in the Minjiang River. Increased river discharge or split ratio of the North Channel resulted in decreased water age and increased DO. Increased nutrient loading and water temperature caused lower DO. In order to protect coastal environments in the Minjiang River, river discharge should be increased and pollutants of local cities should be reduced during the high temperature and drought period. PMID- 27191572 TI - Simulation of antimony adsorption on nano-zero valent iron and kaolinite and analyzing the influencing parameters. AB - Antimony is one of the most toxic pollutants in industrial and mineral wastewaters threatening the life of humans and other creatures. We simulated the adsorption of antimony in the presence of nano-zero valent iron (nZVI) adsorbent, on kaolinite and in the presence of nZVI coated on kaolinite from mineral wastewater using VISUAL MINTEQ 3.1 software. Our aim was to determine the factors affecting the adsorption of antimony by applying simulation. The simulation was performed using an adsorption model of a diffuse layer model. The results of the simulation indicated that the nZVI concentration, initial concentrations of antimony and pH factor are effective on the adsorption of antimony. In the conducted stimulation, the optimum pH was 2-5 and the highest adsorption occurred in an acidic state. With increasing initial concentrations of antimony in the simulation, we concluded that nZVI had absorbed various concentrations above 90% and, by increasing the concentration of nZVI, antimony adsorption rate increased. The increased surface area of nZVI and the expansion of more interchangeable surfaces available for reaction with antimony ions causes more antimony ions to be adsorbed. In all cases, the coefficient of determination between the laboratory results and the model predictions that was obtained was more than 0.9. PMID- 27191571 TI - A novel anoxic-aerobic biofilter process using new composite packing material for the treatment of rural domestic wastewater. AB - A pilot scale experiment was conducted to evaluate the characteristics of contaminants removal in a continuously two-stage biological process composed of an anoxic biofilter (AF) and an biological aerated filter (BAF). This novel process was developed by introducing new composite packing material (MZF) into bioreactors to treat rural domestic wastewater. A comparative study conducted by the same process with ceramsite as packing material under the same conditions showed that a MZF system with a Fe proportion in the packing material performed better in chemical oxygen demand (COD) removal (average 91.5%), ammonia (NH4(+) N) removal (average 98.3%), total nitrogen (TN) removal (average 64.8%) and total phosphorus (TP) removal (average 90%). After treatment of the MZF system, the concentrations of COD, NH4(+)-N, TN and TP in effluent were 20.3 mg/L, 0.5 mg/L, 11.5 mg/L and 0.3 mg/L, respectively. The simultaneously high efficiencies of nitrification, denitrification and phosphorus removal were achieved by the coupling effects of biological and chemical processes in the MZF system. The results of this study showed that the application of MZF might be a favorable choice as packing material in biofilters for treatment of rural domestic wastewater. PMID- 27191573 TI - Carbon sequestration in a surface flow constructed wetland after 12 years of swine wastewater treatment. AB - Constructed wetlands used for the treatment of swine wastewater may potentially sequester significant amounts of carbon. In past studies, we evaluated the treatment efficiency of wastewater in a marsh-pond-marsh design wetland system. The functionality of this system was highly dependent on soil carbon content and organic matter turnover rate. To better understand system performance and carbon dynamics, we measured plant dry matter, decomposition rates and soil carbon fractions. Plant litter decomposition rate was 0.0052 g day(-1) (+/-0.00119 g day(-1)) with an estimated half-life of 133 days. The detritus layer accumulated over the soil surface had much more humin than other C fractions. In marsh areas, soil C extracted with NaOH had four to six times higher amounts of humic acid, fulvic acid and humin than soil C extracted by cold and hot water, HCl/HF, and Na pyruvate. In the pond area, humic acid, fulvic acid and humin content were two to four times lower than in the marsh area. More soil C and N was found in the marsh area than in the pond area. These wetlands proved to be large sinks for stable C forms. PMID- 27191575 TI - Influence of temperature on the activity of anammox granular biomass. AB - The aim of this study was to determine a short-term and long-term effect of temperature on the anammox rate and determination of temperature coefficients in the Arrhenius and Ratkowsky equations. The short-term effects of temperature on the anammox granular biomass were investigated in batch tests at ten different temperatures in the range of 10-55 degrees C. The maximum overall nitrogen removal rate of 1.3 gN gVSS(-1).d(-1) was observed at 40 degrees C (VSS: volatile suspended solids). The minimum rate, close to 0 gN gVSS(-1).d(-1), was observed for the limits of the analyzed temperature range (10 and 55 degrees C). The activity tests carried out at 55 degrees C showed an irreversible loss of the activity due to the observed biomass lysis. Subsequently to the batch tests, a sequencing batch reactor (SBR) was operated at different temperatures (from 30 to 11 degrees C) to determine the long-term effects of temperature. The system was successfully operated at 15 degrees C, but when temperature was decreased to 11 degrees C, nitrite started to accumulate and the system lost its stability. The temperature coefficient (theta) was 1.07 for the batch tests carried out in the temperature range of 10-40 degrees C. In contrast, during the long-term SBR operation, substantially different theta had to be estimated for two temperature ranges, 1.07 (T = 15-30 degrees C) and 1.65 (T = 11-15 degrees C). PMID- 27191574 TI - Meat industry wastewater: microbiological quality and antimicrobial susceptibility of E. coli and Salmonella sp. isolates, case study in Vojvodina, Serbia. AB - Wastewater from meat processing industries is a fusion of compounds with a high load of organic matter, and pathogen microorganisms like Escherichia coli, and Salmonella sp. The aim of this research was to determine microbiological characteristics of the wastewater discharged from the meat processing industry in order to get a more detailed insight into meat industry wastewater pollution, and to evaluate the resistance of bacterial strains E. coli and Salmonella sp. to antibiotics. The evaluation of the antimicrobial susceptibility was performed on 37 strains of E. coli and eight strains of Salmonella sp. to nine different antibiotics. The number of faecal pollution indicators was very high in all samples. From a total of 37 strains of E. coli, a moderate degree of resistance was shown to tetracycline (37.83%); a low degree of resistance to ampicillin (21.62%), streptomycin (24.32%), trimethoprim-sulfamethoxazol (18.92%) and nalidixic acid (16.22%); and very low to: chloramphenicol (13.51%), ciprofloxacin (2.7%), gentamicin and cefotaxime (0.0%). The results for eight strains of Salmonella sp. show that all eight isolates had some degree of susceptibility to nine tested antimicrobial agents and six strains were fully susceptible to all tested antibiotics. PMID- 27191576 TI - Optimization of lamp arrangement in a closed-conduit UV reactor based on a genetic algorithm. AB - The choice for the arrangement of the UV lamps in a closed-conduit ultraviolet (CCUV) reactor significantly affects the performance. However, a systematic methodology for the optimal lamp arrangement within the chamber of the CCUV reactor is not well established in the literature. In this research work, we propose a viable systematic methodology for the lamp arrangement based on a genetic algorithm (GA). In addition, we analyze the impacts of the diameter, angle, and symmetry of the lamp arrangement on the reduction equivalent dose (RED). The results are compared based on the simulated RED values and evaluated using the computational fluid dynamics simulations software ANSYS FLUENT. The fluence rate was calculated using commercial software UVCalc3D, and the GA-based lamp arrangement optimization was achieved using MATLAB. The simulation results provide detailed information about the GA-based methodology for the lamp arrangement, the pathogen transport, and the simulated RED values. A significant increase in the RED values was achieved by using the GA-based lamp arrangement methodology. This increase in RED value was highest for the asymmetric lamp arrangement within the chamber of the CCUV reactor. These results demonstrate that the proposed GA-based methodology for symmetric and asymmetric lamp arrangement provides a viable technical solution to the design and optimization of the CCUV reactor. PMID- 27191577 TI - Copper and cadmium complexation by Cylindrospermopsis raciborskii exudates. AB - Cylindrospermopsis raciborskii is a potentially toxic cyanobacterium that excretes organic materials which act as ligands for metals. Metal ligands may be characterized for their strength of association, e.g., stability constants, which can be either thermodynamic (K) or conditional (K'). In this research we examined K and K' for Cu and Cd complexes with three molecular weight fractions (>30 kDa; 30-10 kDa; 10-3 kDa) of the cyanobacteria EOM. Complexation capacities of the excreted organic materials (EOM) for metals were determined at several ionic strengths (1.0 * 10(-2), 5.0 * 10(-2), 1.0 * 10(-1), and 5.0 * 10(-1) mol L(-1)) at pH 6.6 +/- 0.1, with ligands for which no data for their acidity constants are available; these constants are thus conditional for this specific pH. Bayesian statistics showed that with a probability of 95-100% the EOM have two different ligands for Cu but only one for Cd, that ligands for Cu were stronger than for Cd (94-100% probability), and that the smallest EOM fraction had the highest strength of association for Cu (logKCuL 13.5). The lowest affinity was obtained for Cd (logKCdL 8.6) complexed to any molecular weight fraction. The present findings have important ecological implications, since the metal-ligand association is dynamic, and together with a diversity of ligands it can act as an environmental metal buffer. As a result, higher metal loads may be necessary for the detection of toxicity. PMID- 27191578 TI - Study of kinetics of degradation of cyclohexane carboxylic acid by acclimated activated sludge. AB - Activated sludge contains complex microorganisms, which are highly effective biodegrading agents. In this study, the kinetics of biodegradation of cyclohexane carboxylic acid (CHCA) by an acclimated aerobic activated sludge were investigated. The results showed that after 180 days of acclimation, the activated sludge could steadily degrade >90% of the CHCA in 120 h. The degradation of CHCA by the acclimated activated sludge could be modeled using a first-order kinetics equation. The equations for the degradation kinetics for different initial CHCA concentrations were also obtained. The kinetics constant, kd, decreased with an increase in the CHCA concentration, indicating that, at high concentrations, CHCA had an inhibiting effect on the microorganisms in the activated sludge. The effects of pH on the degradation kinetics of CHCA were also investigated. The results showed that a pH of 10 afforded the highest degradation rate, indicating that basic conditions significantly promoted the degradation of CHCA. Moreover, it was found that the degradation efficiency for CHCA increased with an increase in temperature and concentration of dissolved oxygen under the experimental conditions. PMID- 27191580 TI - Erratum: Water Science and Technology 73 (4), 873-880: Influence of flocculation on sediment deposition process at the Three Gorges Reservoir, Dangwei Wang, Xiaofang Liu, Zuwen Ji, Zhandi Dong and Haihua Hu, doi: 10.2166/wst.2015.562. PMID- 27191579 TI - Utilization of artificial recharged effluent as makeup water for industrial cooling system: corrosion and scaling. AB - The secondary effluent from wastewater treatment plants was reused for industrial cooling water after pre-treatment with a laboratory-scale soil aquifer treatment (SAT) system. Up to a 95.3% removal efficiency for suspended solids (SS), 51.4% for chemical oxygen demand (COD), 32.1% for Cl(-) and 30.0% SO4(2-) were observed for the recharged secondary effluent after the SAT operation, which is essential for controlling scaling and corrosion during the cooling process. As compared to the secondary effluent, the reuse of the 1.5 m depth SAT effluent decreased the corrosion by 75.0%, in addition to a 55.1% decline of the scales/biofouling formation (with a compacted structure). The experimental results can satisfy the Chinese criterion of Design Criterion of the Industrial Circulating Cooling Water Treatment (GB 50050-95), and was more efficient than tertiary effluent which coagulated with ferric chloride. In addition, chemical structure of the scales/biofouling obtained from the cooling system was analyzed. PMID- 27191581 TI - Liposomal Formulation to Increase Stability and Prolong Antineuropathic Activity of Verbascoside. AB - Verbascoside (acteoside) possesses various pharmacological properties for human health, including antioxidant, anti-inflammatory, and antineoplastic properties in addition to numerous wound healing and neuroprotective properties, with an excellent and well-known safety profile. However, its poor chemical stability, due to hydrolysis, limits its use in the clinic. To overcome these limitations, we prepared unilamellar liposomal formulations of verbascoside for parenteral administration.Two formulations were prepared: V-L1 and V-L2, where V-L2 contains phospholipid and cholesterol about 4 times higher than the V-L1 sample, and about 2 times higher than verbascoside. The mean particle size of the liposomes prepared was found to be around 120 nm with a polydispersity index < 0.2. Encapsulation efficacy resulted in 30 %. A total of 82.28 +/- 1.79 % of verbascoside was released from the liposomes within 24 hours. Liposomes ameliorate the stability of verbascoside by preventing its hydrolysis.The optimized drug delivery formulation was tested in the paw pressure test in two animal models of neuropathic pain: a peripheral mononeuropathy was produced either by a chronic constriction injury of the sciatic nerve or by an intra articular injection of sodium monoiodoacetate. The performance of the liposomal formulation was compared with that of the free drug.For evaluating the paw pressure test in chronic constriction injury rats, a liposomal formulation administered i. p. at the dosage of 100 mg/kg showed a longer lasting antihyperalgesic effect in comparison with a 100-mg/kg verbascoside saline solution, as well as in the sodium monoiodoacetate models. The effect appeared 15 min after administration and persisted for up to 60 min. PMID- 27191582 TI - Squarrosine A and Pyrrolhuperzine A, New Lycopodium Alkaloids from Thai and Philippine Huperzia squarrosa. AB - Two new Lycopodium alkaloids, squarrosine A (1) and pyrrolhuperzine A (2), were isolated from the Thai and Philippine plant Huperzia squarrosa. (R)-2 Piperidineacetic acid (5) was a known alkaloid, but has now been isolated for the first time from a natural source. Their structures were elucidated using extensive spectroscopic analyses and, for pyrrolhuperzine A (2), confirmation by chemical transformation. The new compounds exhibited moderate acetylcholinesterase inhibitory activities. PMID- 27191583 TI - Marine Biodiscovery Goes Deeper: Using In Vivo Bioassays Based on Model Organisms to Identify Biomedically Relevant Marine Metabolites. AB - Secondary metabolites from marine organisms are structurally diverse small molecules with high levels of bioactivity, and represent an underutilized resource for modern drug discovery. To facilitate the identification of drug-like marine metabolites, the significant potential of in vivo models of human disease in particular those suitable for medium-throughput screening and bioassay-guided fractionation - should be explored in future marine biodiscovery efforts. Here, we explore the advantages of Caenorhabditis elegans, Drosophila, and zebrafish bioassays for marine biodiscovery, and review recent progress in using these in vivo models to identify bioactive marine metabolites. PMID- 27191584 TI - Fe3O4@Graphene Oxide@Ag Particles for Surface Magnet Solid-Phase Extraction Surface-Enhanced Raman Scattering (SMSPE-SERS): From Sample Pretreatment to Detection All-in-One. AB - A multifunctional magnetic graphene surface-enhanced Raman scattering (SERS) substrate was fabricated successfully by the layer-by-layer assembly of silver and graphene oxide (GO) nanoparticles (NPs) on the magnetic ferroferric oxide particles (Fe3O4@GO@Ag). This ternary particle possesses magnetic properties, SERS activity, and adsorption ability simultaneously. Owing to the multifunction of this Fe3O4@GO@Ag ternary complex, we put forward a new method called a surface magnetic solid-phase extraction (SMSPE) technique, for the SERS detections of pesticide residues on the fruit peels. SMSPE integrates many sample pretreatment procedures, such as surface extraction, separation sample, and detection, all-in one. So this method shows great superiority in simplicity, rapidity, and high efficiency above other standard methods. The whole detection process can be finished within 20 min including the sample pretreatment and SERS detection. Owing to the high density of Ag NPs, the detection sensitivity is high enough that the lowest detectable concentrations are 0.48 and 40 ng/cm(2) for thiram and thiabendazole, which are much lower than the maximal residue limits in fruit prescribed by the U.S. Environmental Protection Agency. This multifunctional ternary particle and its corresponding analytical method have been proven to be applicable for practical samples and also valuable for other surface analysis. PMID- 27191585 TI - To Drug or Not to Drug: A Qualitative Study of Patients' Decision-Making Processes for Managing Insomnia. AB - Treatment preferences play a key role in dictating sleep health outcomes. However, patients' treatment beliefs, attitudes, and experiences that inform preference conceptualization remain an unknown phenomenon. Therefore, this study aims to explore patient perceptions toward pharmacotherapy and the nonpharmacological management of insomnia. Fifty-one patients with insomnia were recruited from specialist clinics and general community settings. Participants completed a brief questionnaire followed by an in-depth semistructured interview that was digitally recorded, transcribed verbatim, and subjected to Framework Analysis to identify emergent themes. Three key themes were identified: Resolving Insomnia, Self-Imposed Treatment Boundaries, and Treatment Uptake. Patients' illness, treatment, and psychosocial beliefs and experiences are closely linked to treatment choice. Being attuned to these influences during the clinical encounter can facilitate treatment selection that is meaningful for the patient. PMID- 27191586 TI - Identification of a mutation causing a defective spindle assembly checkpoint in high ethyl caproate-producing sake yeast strain K1801. AB - In high-quality sake brewing, the cerulenin-resistant sake yeast K1801 with high ethyl caproate-producing ability has been used widely; however, K1801 has a defective spindle assembly checkpoint (SAC). To identify the mutation causing this defect, we first searched for sake yeasts with a SAC-defect like K1801 and found that K13 had such a defect. Then, we searched for a common SNP in only K1801 and K13 by examining 15 checkpoint-related genes in 23 sake yeasts, and found 1 mutation, R48P of Cdc55, the PP2A regulatory B subunit that is important for the SAC. Furthermore, we confirmed that the Cdc55-R48P mutation was responsible for the SAC-defect in K1801 by molecular genetic analyses. Morphological analysis indicated that this mutation caused a high cell morphological variation. But this mutation did not affect the excellent brewing properties of K1801. Thus, this mutation is a target for breeding of a new risk free K1801 with normal checkpoint integrity. PMID- 27191587 TI - Social Workers as Workplace-Based Instructors of Alcohol and Drug Screening, Brief Intervention, and Referral to Treatment (SBIRT) for Emergency Medicine Residents. AB - PROBLEM: Residency education is challenged by a shortage of personnel and time, particularly for teaching behavioral interventions such as screening, brief intervention, and referral to treatment (SBIRT) to reduce hazardous drinking and drug use. However, social workers may be well placed to teach SBIRT in clinical training settings. INTERVENTION: We describe a curriculum with social workers as SBIRT trainers of emergency medicine (EM) residents during actual clinical shifts in an EM residency training program. The curriculum required 1 EM faculty member working with social workers and 1 additional hour of formal residency conference teaching time. CONTEXT: We implemented the curriculum at both a university tertiary care hospital emergency department and a county trauma center. We trained 8 social workers at both sites as SBIRT superusers to teach and assess EM resident SBIRT performance with actual patients. We measured the length and number of sessions to attain SBIRT competence, residents' satisfaction, and resident comments (coded by authors). OUTCOME: Five of the 8 social workers trained residents between June 2013 and May 2014, 31 EM residents trained to a level indicating SBIRT competence with 114 patients. Each patient interaction averaged 8.8 minutes and residents averaged 3.13 patients. Twenty-four (77%) residents gave ratings of 1.58 (SD = .58) for the quality of teaching, 2.33 (SD = .87) for recommending the training to a colleague, 1.38 (SD = .49) for superusers' knowledge, 1.88 (SD = .95) for usefulness of instruction, 1.54 (SD = .72) for workplace learning, and 1.58 (SD = .78) for valuing learning from social workers (on a scale of 1 [very satisfied/strongly agree] to 5 [very dissatisfied/strongly disagree]). Residents preferred learning SBIRT during the 1st and 2nd training years and in the workplace. LESSONS LEARNED: Social work colleagues can be effective in teaching SBIRT to residents in the workplace, and our residents highly valued learning from social workers, who all had prior training in motivational interviewing. In the implementation of this curriculum, the clinical demands of residents must be taken into account when teaching occurs, and having multiple social worker instructors was instrumental. PMID- 27191588 TI - Prevalence and antibiotic resistance of commensal Streptococcus pneumoniae in nine European countries. AB - The human microbiota represents an important reservoir of antibiotic resistance. Moreover, the majority of antibiotics are prescribed in primary care. For this reason, we assessed the prevalence and antibiotic resistance of nasal carriage strains of Streptococcus pneumoniae, the most prevalent bacterial causative agent of community-acquired respiratory tract infections, in outpatients in nine European countries. Nasal swabs were collected between October 2010 and May 2011, from 32,770 patients, recruited by general practices in nine European countries. Overall prevalence of S. pneumoniae nasal carriage in the nine countries was 2.9%. The carriage was higher in men (3.7%) than in women (2.7%). Children (4-9 years) had a higher carriage prevalence (27.2%) compared with those older than 10 years (1.9%). The highest resistance observed was to cefaclor. The highest prevalence of multidrug resistance was found in Spain and the lowest prevalence was observed in Sweden. PMID- 27191589 TI - Use of Population Genetics to Assess the Ecology, Evolution, and Population Structure of Coccidioides. AB - During the past 20 years, a general picture of the genetic diversity and population structure of Coccidioides, the causal agent of coccidioidomycosis (Valley fever), has emerged. The genus consists of 2 genetically diverse species, C. immitis and C. posadasii, each of which contains 1 or more distinct populations with limited gene flow. Genotypic data indicate that C. immitis is divided into 2 subpopulations (central and southern California populations) and C. posadasii is divided into 3 subpopulations (Arizona, Mexico, and Texas/South America populations). However, admixture within and among these populations and the current paucity of environmental isolates limit our understanding of the population genetics of Coccidioides. We assessed population structure of Coccidioides in Arizona by analyzing 495 clinical and environmental isolates. Our findings confirm the population structure as previously described and indicate a finer scale population structure in Arizona. Environmental isolates appear to have higher genetic diversity than isolates from human patients. PMID- 27191590 TI - Fission Yeast SCYL1/2 Homologue Ppk32: A Novel Regulator of TOR Signalling That Governs Survival during Brefeldin A Induced Stress to Protein Trafficking. AB - Target of Rapamycin (TOR) signalling allows eukaryotic cells to adjust cell growth in response to changes in their nutritional and environmental context. The two distinct TOR complexes (TORC1/2) localise to the cell's internal membrane compartments; the endoplasmic reticulum (ER), Golgi apparatus and lysosomes/vacuoles. Here, we show that Ppk32, a SCYL family pseudo-kinase, is a novel regulator of TOR signalling. The absence of ppk32 expression confers resistance to TOR inhibition. Ppk32 inhibition of TORC1 is critical for cell survival following Brefeldin A (BFA) induced stress. Treatment of wild type cells with either the TORC1 specific inhibitor rapamycin or the general TOR inhibitor Torin1 confirmed that a reduction in TORC1 activity promoted recovery from BFA induced stress. Phosphorylation of Ppk32 on two residues that are conserved within the SCYL pseudo-kinase family are required for this TOR inhibition. Phosphorylation on these sites controls Ppk32 protein levels and sensitivity to BFA. BFA induced ER stress does not account for the response to BFA that we report here, however BFA is also known to induce Golgi stress and impair traffic to lysosomes. In summary, Ppk32 reduce TOR signalling in response to BFA induced stress to support cell survival. PMID- 27191592 TI - In Vivo Chromatin Targets of the Transcription Factor Yin Yang 2 in Trophoblast Stem Cells. AB - BACKGROUND: Yin Yang 2 (YY2) is a zinc finger protein closely related to the well characterized Yin Yang 1 (YY1). YY1 is a DNA-binding transcription factor, with defined functions in multiple developmental processes, such as implantation, cell differentiation, X inactivation, imprinting and organogenesis. Yy2 has been treated as a largely immaterial duplication of Yy1, as they share high homology in the Zinc Finger-region and similar if not identical in vitro binding sites. In contrast to these similarities, gene expression alterations in HeLa cells with attenuated levels of either Yy1 or Yy2 were to some extent gene-specific. Moreover, the chromatin binding sites for YY2, except for its association with transposable retroviral elements (RE) and Endogenous Retroviral Elements (ERVs), remain to be identified. As a first step towards defining potential Yy2 functions matching or complementary to Yy1, we considered in vivo DNA binding sites of YY2 in trophoblast stem (TS) cells. RESULTS: We report the presence of YY2 protein in mouse-derived embryonic stem (ES) and TS cell lines. Following up on our previous report on ERV binding by YY2 in TS cells, we investigated the tissue-specificity of REX1 and YY2 binding and confirm binding to RE/ERV targets in both ES cells and TS cells. Because of the higher levels of expression, we chose TS cells to understand the role of Yy2 in gene and chromatin regulation. We used in vivo YY2 association as a measure to identify potential target genes. Sequencing of chromatin obtained in chromatin-immunoprecipitation (ChIP) assays carried out with alphaYY2 serum allowed us to identify a limited number of chromatin targets for YY2. Some putative binding sites were validated in regular ChIP assays and gene expression of genes nearby was altered in the absence of Yy2. CONCLUSIONS: YY2 binding to ERVs is not confined to TS cells. In vivo binding sites share the presence of a consensus binding motif. Selected sites were uniquely bound by YY2 as opposed to YY1, suggesting that YY2 exerts unique contributions to gene regulation. YY2 binding was not generally associated with gene promoters. However, several YY2 binding sites are linked to long noncoding RNA (lncRNA) genes and we show that the expression levels of a few of those are Yy2-dependent. PMID- 27191591 TI - Identification of a Transcription Factor That Regulates Host Cell Exit and Virulence of Mycobacterium tuberculosis. AB - The interaction of Mycobacterium tuberculosis (Mtb) with host cell death signaling pathways is characterized by an initial anti-apoptotic phase followed by a pro-necrotic phase to allow for host cell exit of the bacteria. The bacterial modulators regulating necrosis induction are poorly understood. Here we describe the identification of a transcriptional repressor, Rv3167c responsible for regulating the escape of Mtb from the phagosome. Increased cytosolic localization of MtbDeltaRv3167c was accompanied by elevated levels of mitochondrial reactive oxygen species and reduced activation of the protein kinase Akt, and these events were critical for the induction of host cell necrosis and macroautophagy. The increase in necrosis led to an increase in bacterial virulence as reflected in higher bacterial burden and reduced survival of mice infected with MtbDeltaRv3167c. The regulon of Rv3167c thus contains the bacterial mediators involved in escape from the phagosome and host cell necrosis induction, both of which are crucial steps in the intracellular lifecycle and virulence of Mtb. PMID- 27191594 TI - A Conserved Epitope Mapped with a Monoclonal Antibody against the VP3 Protein of Goose Parvovirus by Using Peptide Screening and Phage Display Approaches. AB - BACKGROUND: Waterfowl parvovirus (WPV) infection causes high mortality and morbidity in both geese (Anser anser) and Muscovy ducks (Cairina moschata), resulting in significant losses to the waterfowl industries. The VP3 protein of WPV is a major structural protein that induces neutralizing antibodies in the waterfowl. However, B-cell epitopes on the VP3 protein of WPV have not been characterized. METHODS AND RESULTS: To understand the antigenic determinants of the VP3 protein, we used the monoclonal antibody (mAb) 4A6 to screen a set of eight partially expressed overlapping peptides spanning VP3. Using western blotting and an enzyme-linked immunosorbent assay (ELISA), we localized the VP3 epitope between amino acids (aa) 57 and 112. To identify the essential epitope residues, a phage library displaying 12-mer random peptides was screened with mAb 4A6. Phage clone peptides displayed a consensus sequence of YxRFHxH that mimicked the sequence 82Y/FNRFHCH88, which corresponded to amino acid residues 82 to 88 of VP3 protein of WPVs. mAb 4A6 binding to biotinylated fragments corresponding to amino acid residues 82 to 88 of the VP3 protein verified that the 82FxRFHxH88 was the VP3 epitope and that amino acids 82F is necessary to retain maximal binding to mAb 4A6. Parvovirus-positive goose and duck sera reacted with the epitope peptide by dot blotting assay, revealing the importance of these amino acids of the epitope in antibody-epitope binding reactivity. CONCLUSIONS AND SIGNIFICANCE: We identified the motif FxRFHxH as a VP3-specific B-cell epitope that is recognized by the neutralizing mAb 4A6. This finding might be valuable in understanding of the antigenic topology of VP3 of WPV. PMID- 27191593 TI - Mycobacterium massiliense Induces Macrophage Extracellular Traps with Facilitating Bacterial Growth. AB - Human neutrophils have been known to release neutrophil extracellular traps (NETs), antimicrobial DNA structures capable of capturing and killing microbes. Recently, a similar phenomenon has been reported in macrophages infected with various pathogens. However, a role for macrophages extracellular traps (METs) in host defense responses against Mycobacterium massiliense (M. mass) has yet to be described. In this study, we show that M. mass, a rapid growing mycobacterium (RGM), also induces the release of METs from PMA-differentiated THP-1 cells. Intriguingly, this process is not dependent on NADPH oxidase activity, which regulates NET formation. Instead, M. mass-induced MET formation partially depends on calcium influx and requires phagocytosis of high bacterial load. The METs consist of a DNA backbone embedded with microbicidal proteins such as histone, MPO and elastase. Released METs entrap M. mass and prevent their dissemination, but do not have bactericidal activity. Instead, they result in enhanced bacterial growth. In this regard, METs were considered to provide interaction of M. mass with cells and an environment for bacterial aggregation, which may facilitate mycobacterial survival and growth. In conclusion, our results demonstrate METs as an innate defense response against M. mass infection, and suggest that extracellular traps play a multifaceted role in the interplay between host and bacteria. PMID- 27191596 TI - Overexpression of Actinidia deliciosa pyruvate decarboxylase 1 gene enhances waterlogging stress in transgenic Arabidopsis thaliana. AB - Ethanolic fermentation is classically associated with waterlogging tolerance when plant cells switch from respiration to anaerobic fermentation. Pyruvate decarboxylase (PDC), which catalyzes the first step in this pathway, is thought to be the main regulatory enzyme. Here, we cloned a full-length PDC cDNA sequence from kiwifruit, named AdPDC1. We determined the expression of the AdPDC1 gene in kiwifruit under different environmental stresses using qRT-PCR, and the results showed that the increase of AdPDC1 expression during waterlogging stress was much higher than that during salt, cold, heat and drought stresses. Overexpression of kiwifruit AdPDC1 in transgenic Arabidopsis enhanced the resistance to waterlogging stress but could not enhance resistance to cold stress at five weeks old seedlings. Overexpression of kiwifruit AdPDC1 in transgenic Arabidopsis could not enhance resistance to NaCl and mannitol stresses at the stage of seed germination and in early seedlings. These results suggested that the kiwifruit AdPDC1 gene is required during waterlogging but might not be required during other environmental stresses. Expression of the AdPDC1 gene was down-regulated by abscisic acid (ABA) in kiwifruit, and overexpression of the AdPDC1 gene in Arabidopsis inhibited seed germination and root length under ABA treatment, indicating that ABA might negatively regulate the AdPDC1 gene under waterlogging stress. PMID- 27191595 TI - JC Polyomavirus Abundance and Distribution in Progressive Multifocal Leukoencephalopathy (PML) Brain Tissue Implicates Myelin Sheath in Intracerebral Dissemination of Infection. AB - Over half of adults are seropositive for JC polyomavirus (JCV), but rare individuals develop progressive multifocal leukoencephalopathy (PML), a demyelinating JCV infection of the central nervous system. Previously, PML was primarily seen in immunosuppressed patients with AIDS or certain cancers, but it has recently emerged as a drug safety issue through its association with diverse immunomodulatory therapies. To better understand the relationship between the JCV life cycle and PML pathology, we studied autopsy brain tissue from a 70-year-old psoriasis patient on the integrin alpha-L inhibitor efalizumab following a ~2 month clinical course of PML. Sequence analysis of lesional brain tissue identified PML-associated viral mutations in regulatory (non-coding control region) DNA, capsid protein VP1, and the regulatory agnoprotein, as well as 9 novel mutations in capsid protein VP2, indicating rampant viral evolution. Nine samples, including three gross PML lesions and normal-appearing adjacent tissues, were characterized by histopathology and subject to quantitative genomic, proteomic, and molecular localization analyses. We observed a striking correlation between the spatial extent of demyelination, axonal destruction, and dispersion of JCV along white matter myelin sheath. Our observations in this case, as well as in a case of PML-like disease in an immunocompromised rhesus macaque, suggest that long-range spread of polyomavirus and axonal destruction in PML might involve extracellular association between virus and the white matter myelin sheath. PMID- 27191597 TI - Novel Mutations in the Voltage-Gated Sodium Channel of Pyrethroid-Resistant Varroa destructor Populations from the Southeastern USA. AB - The parasitic mite Varroa destructor has a significant worldwide impact on bee colony health. In the absence of control measures, parasitized colonies invariably collapse within 3 years. The synthetic pyrethroids tau-fluvalinate and flumethrin have proven very effective at managing this mite within apiaries, but intensive control programs based mainly on one active ingredient have led to many reports of pyrethroid resistance. In Europe, a modification of leucine to valine at position 925 (L925V) of the V. destructor voltage-gated sodium channel was correlated with resistance, the mutation being found at high frequency exclusively in hives with a recent history of pyrethroid treatment. Here, we identify two novel mutations, L925M and L925I, in tau-fluvalinate resistant V. destructor collected at seven sites across Florida and Georgia in the Southeastern region of the USA. Using a multiplexed TaqMan(r) allelic discrimination assay, these mutations were found to be present in 98% of the mites surviving tau-fluvalinate treatment. The mutations were also found in 45% of the non-treated mites, suggesting a high potential for resistance evolution if selection pressure is applied. The results from a more extensive monitoring programme, using the Taqman(r) assay described here, would clearly help beekeepers with their decision making as to when to include or exclude pyrethroid control products and thereby facilitate more effective mite management programmes. PMID- 27191598 TI - Ocelot (Leopardus pardalis) Density in Central Amazonia. AB - Ocelots (Leopardus pardalis) are presumed to be the most abundant of the wild cats throughout their distribution range and to play an important role in the dynamics of sympatric small-felid populations. However, ocelot ecological information is limited, particularly for the Amazon. We conducted three camera trap surveys during three consecutive dry seasons to estimate ocelot density in Amana Reserve, Central Amazonia, Brazil. We implemented a spatial capture recapture (SCR) model that shared detection parameters among surveys. A total effort of 7020 camera-trap days resulted in 93 independent ocelot records. The estimate of ocelot density in Amana Reserve (24.84 +/- SE 6.27 ocelots per 100 km2) was lower than at other sites in the Amazon and also lower than that expected from a correlation of density with latitude and rainfall. We also discuss the importance of using common parameters for survey scenarios with low recapture rates. This is the first density estimate for ocelots in the Brazilian Amazon, which is an important stronghold for the species. PMID- 27191599 TI - Photochemical Generation of Benzyl Cations That Selectively Cross-Link Guanine and Cytosine in DNA. AB - UV irradiation of several aryl boronates efficiently produced bifunctional benzyl cations that selectively form guanine-cytosine cross-links in DNA. Photoinduced homolysis of the C-Br bond took place with the aryl boronate bromides 3a and 4a, generating free radicals that were oxidized to benzyl cations via electron transfer. However, photoirradiation of the quaternary ammonium salts 3b and 4b led to heterolysis of C-N bond, directly producing benzyl cations. The electron donating group in the aromatic ring greatly enhanced cross-linking efficiency. PMID- 27191601 TI - Response to comment on "Exposure-response modeling of non-cancer effects in humans exposed to Libby Amphibole Asbestos; update" by Benson et al. (2015) submitted by Goodman et al. (2016). PMID- 27191600 TI - Genome-Wide Association Mapping of Anther Extrusion in Hexaploid Spring Wheat. AB - In a number of crop species hybrids are able to outperform line varieties. The anthers of the autogamous bread wheat plant are normally extruded post anthesis, a trait which is unfavourable for the production of F1 hybrid grain. Higher anther extrusion (AE) promotes cross fertilization for more efficient hybrid seed production. Therefore, this study aimed at the genetic dissection of AE by genome wide association studies (GWAS) and determination of the main effect QTL. We applied GWAS approach to identify DArT markers potentially linked to AE to unfold its genetic basis in a panel of spring wheat accessions. Phenotypic data were collected for three years and best linear unbiased estimate (BLUE) values were calculated across all years. The extent of the AE correlation between growing years and BLUE values ranged from r = +0.56 (2013 vs 2015) to 0.91 (2014 vs BLUE values). The broad sense heritability was 0.84 across all years. Six accessions displayed stable AE >80% across all the years. Genotyping data included 2,575 DArT markers (with minimum of 0.05 minor allele frequency applied). AE was influenced both by genotype and by the growing environment. In all, 131 significant marker trait associations (MTAs) (|log10 (P)| >FDR) were established for AE. AE behaved as a quantitative trait, with five consistently significant markers (significant across at least two years with a significant BLUE value) contributing a minor to modest proportion (4.29% to 8.61%) of the phenotypic variance and affecting the trait either positively or negatively. For this reason, there is potential for breeding for improved AE by gene pyramiding. The consistently significant markers linked to AE could be helpful for marker assisted selection to transfer AE to high yielding varieties allowing to promote the exploitation of hybrid-heterosis in the key crop wheat. PMID- 27191602 TI - Patterns of Coral-Reef Finfish Species Disappearances Inferred from Fishers' Knowledge in Global Epicentre of Marine Shorefish Diversity. AB - In the Philippines, very high fishing pressure coincides with the globally greatest number of shorefish species, yet no long-term fisheries data are available to explore species-level changes that may have occurred widely in the most species rich and vulnerable marine ecosystem, namely coral reefs. Through 2655 face-to-face interviews conducted between August 2012 and July 2014, we used fishers' recall of past catch rates of reef-associated finfish to infer species disappearances from catches in five marine key biodiversity areas (Lanuza Bay, Danajon Bank, Verde Island Passage, Polillo Islands and Honda Bay). We modeled temporal trends in perceived catch per unit effort (CPUE) based on fishers' reports of typical good days' catches using Generalized Linear Mixed Modelling. Fifty-nine different finfish disappeared from catches between the 1950s and 2014; 42 fish were identified to species level, two to genus, seven to family and eight to local name only. Five species occurring at all sites with the greatest number of fishers reporting zero catches were the green bumphead parrotfish (Bolbometopon muricatum), humphead wrasse (Cheilinus undulatus), African pompano (Alectis ciliaris), giant grouper (Epinephelus lanceolatus) and mangrove red snapper (Lutjanus argentimaculatus). Between the 1950s and 2014, the mean perceived CPUE of bumphead parrotfish declined by 88%, that of humphead wrasse by 82%, African pompano by 66%, giant grouper by 74% and mangrove red snapper by 64%. These declines were mainly associated with excess and uncontrolled fishing, fish life-history traits like maximum body size and socio-economic factors like access to market infrastructure and services, and overpopulation. The fishers' knowledge is indicative of extirpations where evidence for these losses was otherwise lacking. Our models provide information as basis for area-based conservation and regional resource management particularly for the more vulnerable, once common, large, yet wide-ranging reef finfish species. PMID- 27191603 TI - Derivation, Characterization, and Neural Differentiation of Integration-Free Induced Pluripotent Stem Cell Lines from Parkinson's Disease Patients Carrying SNCA, LRRK2, PARK2, and GBA Mutations. AB - We report generation of induced pluripotent stem cell (iPSC) lines from ten Parkinson's disease (PD) patients carrying SNCA, PARK2, LRRK2, and GBA mutations, and one age-matched control. After validation of pluripotency, long-term genome stability, and integration-free reprogramming, eight of these lines (one of each SNCA, LRRK2 and GBA, four PARK2 lines, and the control) were differentiated into neural stem cells (NSC) and subsequently to dopaminergic cultures. We did not observe significant differences in the timeline of neural induction and NSC derivation between the patient and control line, nor amongst the patient lines, although we report considerable variability in the efficiency of dopaminergic differentiation among patient lines. We performed whole genome expression analyses of the lines at each stage of differentiation (fibroblast, iPSC, NSC, and dopaminergic culture) in an attempt to identify alterations by large-scale evaluation. While gene expression profiling clearly distinguished cells at different stages of differentiation, no mutation-specific clustering or difference was observed, though consistent changes in patient lines were detected in genes associated mitochondrial biology. We further examined gene expression in a stress model (MPTP-induced dopaminergic neuronal death) using two clones from the SNCA triplication line, and detected changes in genes associated with mitophagy. Our data suggested that even a well-characterized line of a monogenic disease may not be sufficient to determine the cause or mechanism of the disease, and highlights the need to use more focused strategies for large-scale data analysis. PMID- 27191604 TI - Morphometric analysis of feedforward pathways from the primary somatosensory area (S1) of rats. AB - We used biotinylated dextran amine (BDA) to anterogradely label individual axons projecting from primary somatosensory cortex (S1) to four different cortical areas in rats. A major goal was to determine whether axon terminals in these target areas shared morphometric similarities based on the shape of individual terminal arbors and the density of two bouton types: en passant (Bp) and terminaux (Bt). Evidence from tridimensional reconstructions of isolated axon terminal fragments (n=111) did support a degree of morphological heterogeneity establishing two broad groups of axon terminals. Morphological parameters associated with the complexity of terminal arbors and the proportion of beaded Bp vs stalked Bt were found to differ significantly in these two groups following a discriminant function statistical analysis across axon fragments. Interestingly, both groups occurred in all four target areas, possibly consistent with a commonality of presynaptic processing of tactile information. These findings lay the ground for additional work aiming to investigate synaptic function at the single bouton level and see how this might be associated with emerging properties in postsynaptic targets. PMID- 27191605 TI - Altered mean platelet volume in patients with polymyositis and its association with disease severity. AB - Polymyositis (PM) is an autoimmune disease characterized by chronic inflammation in skeletal muscle. Mean platelet volume (MPV), a marker in the assessment of systemic inflammation, is easily measured by automatic blood count equipment. However, to our knowledge, there are no data in the literature with respect to MPV levels in PM patients. Therefore, in this study we aimed to investigate MPV levels in patients with PM. This study included 92 newly diagnosed PM patients and 100 healthy individuals. MPV levels were found to be significantly lower compared with healthy controls (10.3+/-1.23 vs 11.5+/-0.74 fL, P<0.001). Interestingly, MPV was found to be positively correlated with manual muscle test (MMT) score and negatively correlated with erythrocyte sedimentation rate (ESR) in patients with PM (r=0.239, P=0.022; r=-0.268, P=0.010, respectively). In addition, MPV was significantly lower in active PM patients compared with inactive PM patients (9.9+/-1.39 vs 10.6+/-0.92 fL, P=0.010). MPV was independently associated with PM in multivariate regression analyses, when controlling for hemoglobin and ESR (OR=0.312, P=0.031, 95%CI=0.108 to 0.899). The ROC curve analysis for MPV in estimating PM patients resulted in an area under the curve of 0.800, with sensitivity of 75.0% and specificity of 67.4%. Our results suggest that MPV is inversely correlated with disease activity in patients with PM. MPV might be a useful tool for rapid assessment of disease severity in PM patients. PMID- 27191606 TI - Involvement of the TRPV1 channel in the modulation of spontaneous locomotor activity, physical performance and physical exercise-induced physiological responses. AB - Physical exercise triggers coordinated physiological responses to meet the augmented metabolic demand of contracting muscles. To provide adequate responses, the brain must receive sensory information about the physiological status of peripheral tissues and organs, such as changes in osmolality, temperature and pH. Most of the receptors involved in these afferent pathways express ion channels, including transient receptor potential (TRP) channels, which are usually activated by more than one type of stimulus and are therefore considered polymodal receptors. Among these TRP channels, the TRPV1 channel (transient receptor potential vanilloid type 1 or capsaicin receptor) has well-documented functions in the modulation of pain sensation and thermoregulatory responses. However, the TRPV1 channel is also expressed in non-neural tissues, suggesting that this channel may perform a broad range of functions. In this review, we first present a brief overview of the available tools for studying the physiological roles of the TRPV1 channel. Then, we present the relationship between the TRPV1 channel and spontaneous locomotor activity, physical performance, and modulation of several physiological responses, including water and electrolyte balance, muscle hypertrophy, and metabolic, cardiovascular, gastrointestinal, and inflammatory responses. Altogether, the data presented herein indicate that the TPRV1 channel modulates many physiological functions other than nociception and thermoregulation. In addition, these data open new possibilities for investigating the role of this channel in the acute effects induced by a single bout of physical exercise and in the chronic effects induced by physical training. PMID- 27191607 TI - Histidine-tryptophan-ketoglutarate solution decreases mortality and morbidity in high-risk patients with severe pulmonary arterial hypertension associated with complex congenital heart disease: an 11-year experience from a single institution. AB - Cardioplegic reperfusion during a long term ischemic period interrupts cardiac surgery and also increases cellular edema due to repeated solution administration. We reviewed the clinical experiences on myocardial protection of a single perfusion with histidine-tryptophan-ketoglutarate (HTK) for high-risk patients with severe pulmonary arterial hypertension associated with complex congenital heart disease. This retrospective study included 101 high-risk patients undergoing arterial switch operation between March 2001 and July 2012. We divided the cohort into two groups: HTK group, myocardial protection was carried out with one single perfusion with HTK solution; and St group, myocardial protection with conventional St. Thomas' crystalloid cardioplegic solution. The duration of cardiopulmonary bypass did not differ between the two groups. The mortality, morbidity, ICU stay, post-operative hospitalization time, and number of transfusions in HTK group were lower than those in St group (P<0.05). Univariate and multivariate analysis showed that HTK is a statistically significant independent predictor of decreased early mortality and morbidity (P<0.05). In conclusion, HTK solution seems to be an effective and safe alternative to St. Thomas' solution for cardioplegic reperfusion in high-risk patients with complex congenital heart disease. PMID- 27191608 TI - Random-start controlled ovarian stimulation for emergency fertility preservation in a patient with myelodysplastic syndrome: a case report. AB - This study reports a case of a gonadotropin-releasing hormone agonist trigger in a young female with myelodysplastic syndrome (MDS) who underwent fertility preservation using random-start controlled ovarian stimulation. This method involves the stimulation of the ovary regardless of a patient's menstrual-cycle phase. A review of the related literature is also provided. A 17-year-old patient was diagnosed with MDS and required initiation of peripheral blood stem cell transplantation within a maximum of 3 weeks and was in the luteal phase of the menstrual cycle when the possibility of attempting preservation of fertility was presented to her. She opted for a random-start controlled ovarian stimulation with gonadotropins. With successful hemorrhagic prophylaxis, 17 oocytes were retrieved including 10 mature and 7 immature oocytes. Of the immature oocytes, 3 were successfully matured in vitro and a vitrification protocol was used to freeze the 13 mature oocytes. PMID- 27191609 TI - Novel retrograde puncture method to establish preperitoneal space for laparoscopic direct inguinal hernia repair with internal ring suturing. AB - The aim of this study was to explore the clinical efficacy of a novel retrograde puncture approach to establish a preperitoneal space for laparoscopic direct inguinal hernia repair with inguinal ring suturing. Forty-two patients who underwent laparoscopic inguinal hernia repair with retrograde puncture for preperitoneal space establishment as well as inguinal ring suturing between August 2013 and March 2014 at our hospital were enrolled. Preperitoneal space was successfully established in all patients, with a mean establishment time of 6 min. Laparoscopic repairs were successful in all patients, with a mean surgical time of 26+/-15.1 min. Mean postoperative hospitalization duration was 3.0+/-0.7 days. Two patients suffered from postoperative local hematomas, which were relieved after puncturing and drainage. Four patients had short-term local pain. There were no cases of chronic pain. Patients were followed up for 6 months to 1 year, and no recurrence was observed. Our results demonstrate that preperitoneal space established by the retrograde puncture technique can be successfully used in adult laparoscopic hernioplasty to avoid intraoperative mesh fixation, and thus reduce medical costs. PMID- 27191610 TI - Analysis of foveal characteristics and their asymmetries in the normal population. AB - The advance of optical coherence tomography (OCT) enables a detailed examination of the human retina in-vivo for clinical routine and experimental eye research. Only few investigations to date captured human foveal morphology in a large subject group on the basis of a detailed analysis employing mathematical models. However, even for important foveal characteristics unified terminology and clear definitions were not implemented so far. This might be a reason, why to this day the human fovea is considered to be a mostly symmetric and round structure. Therefore, the most important finding of this work is the detailed analysis of the asymmetric structure of the human fovea. We employed five clinically highly relevant foveal characteristics, which are derived from a previously published fovea model. For each, an accurate mathematical description is given. The presented properties include (1) mean retinal thickness inside a defined radius, (2) foveal bowl area, (3) a new, exact definition of foveal radius, (4) maximum foveal slope, and (5) the maximum height of the foveal rim. Furthermore, minimum retinal thickness was derived and analyzed. 220 strictly controlled healthy Caucasian subjects of European decent with an even distribution of age and gender were imaged with an Heidelberg Spectralis OCT. Detailed analysis demonstrated the following general results: (1) significant gender difference regarding the central foveal subfield thickness (CFST) but no significant differences for the minimum central retinal thickness, (2) a strong correlation between right and left eye of the same subject, and, as essential finding, (3) strong structural differences of the fovea form in the different anatomical directions (nasal, temporal, inferior and superior). In the analysis of the foveal asymmetry, it will be demonstrated that the foveal radius is larger in nasal and temporal direction compared to inferior and superior position. Furthermore, it will be shown that the circular fovea rather has an elliptic form with the larger axis along the nasal to temporal direction. Interestingly, the foveal slope shows a divergent behavior as the temporal direction has the smallest slope angle and both, inferior and superior angles are clearly larger than the others. The findings in this work can be used for an exact quantification of changes in early stages of various retinal diseases and as a marker for initial diagnosis. PMID- 27191611 TI - Changes in aquaporin-4 and Kir4.1 expression in rats with inherited retinal dystrophy. AB - Muller glial cells (MGC) are essential for normal functioning of retina. They are especially involved in potassium (K+) and water homeostasis, via inwardly rectifying K+ (Kir 4.1) and aquaporin-4 (AQP4) channels respectively. Because MGC appear morphologically and functionally altered in most retinal pathologies, we studied the expression of AQP 4 and Kir 4.1 during the time course of progressive retinal degeneration in Royal College of Surgeons (RCS) rats, an animal model for the hereditary human retinal degenerative disease Retinitis pigmentosa. Simultaneous detection of AQP4 and Kir 4.1 was performed by quantitative real time polymerase chain reaction (QRT-PCR), Western blot and immunohistochemistry at birth and during progression of the pathology. Although small quantities of AQP4 and Kir 4.1 mRNA were detected at birth (postnatal day (PNd) 0) in both control and dystrophic rat retinas, proteins could not be detected at this age. Detectable proteins appeared in the second week of postnatal life. From PNd15 onwards, the time course in the expression of both AQP4 and Kir 4.1 mRNAs and protein was similar in dystrophic and control rats, with a progressive increase peaking at PNd60 and a subsequent decrease by one year. AQP4 protein and mRNA content were significantly lowered in dystrophic compared to control rats. Kir 4.1 protein levels were also lower in dystrophic retinas, while mRNA concentrations were unchanged and/or slightly higher in dystrophic rats. The discrepancies between Kir4.1 mRNA and protein suggest perturbation in protein translation due to the pathology. AQP4 and Kir 4.1/vimentin co-immunolabeling showed that: 1) apical radial processes of some MGC invaded the subretinal zone, and 2) MGC morphology was distorted in advanced pathology. MGC became hypertrophic both during the pathology and also with age in control rats. In conclusion, our results confirm that this inherited photoreceptor degeneration also leads to progressive alterations in physiological and morphological parameters of MGC which may aggravate retinal impairment. PMID- 27191612 TI - Antimicrobial Susceptibility of Enteric Gram Negative Facultative Anaerobe Bacilli in Aerobic versus Anaerobic Conditions. AB - Antimicrobial treatments result in the host's enteric bacteria being exposed to the antimicrobials. Pharmacodynamic models can describe how this exposure affects the enteric bacteria and their antimicrobial resistance. The models utilize measurements of bacterial antimicrobial susceptibility traditionally obtained in vitro in aerobic conditions. However, in vivo enteric bacteria are exposed to antimicrobials in anaerobic conditions of the lower intestine. Some of enteric bacteria of food animals are potential foodborne pathogens, e.g., Gram-negative bacilli Escherichia coli and Salmonella enterica. These are facultative anaerobes; their physiology and growth rates change in anaerobic conditions. We hypothesized that their antimicrobial susceptibility also changes, and evaluated differences in the susceptibility in aerobic vs. anaerobic conditions of generic E. coli and Salmonella enterica of diverse serovars isolated from cattle feces. Susceptibility of an isolate was evaluated as its minimum inhibitory concentration (MIC) measured by E-Test(r) following 24 hours of adaptation to the conditions on Mueller-Hinton agar, and on a more complex tryptic soy agar with 5% sheep blood (BAP) media. We considered all major antimicrobial drug classes used in the U.S. to treat cattle: beta-lactams (specifically, ampicillin and ceftriaxone E-Test(r)), aminoglycosides (gentamicin and kanamycin), fluoroquinolones (enrofloxacin), classical macrolides (erythromycin), azalides (azithromycin), sulfanomides (sulfamethoxazole/trimethoprim), and tetracyclines (tetracycline). Statistical analyses were conducted for the isolates (n>=30) interpreted as susceptible to the antimicrobials based on the clinical breakpoint interpretation for human infection. Bacterial susceptibility to every antimicrobial tested was statistically significantly different in anaerobic vs. aerobic conditions on both media, except for no difference in susceptibility to ceftriaxone on BAP agar. A satellite experiment suggested that during first days in anaerobic conditions the susceptibility changes with time. The results demonstrate that assessing effects of antimicrobial treatments on resistance in the host's enteric bacteria that are Gram negative facultative Anaerobe Bacilli requires data on the bacterial antimicrobial susceptibility in the conditions resembling those in the intestine. PMID- 27191613 TI - Synthesis of alpha-santonin derived acetyl santonous acid triazole derivatives and their bioevaluation for T and B-cell proliferation. AB - A new series of alpha-santonin derived acetyl santonous acid 1,2,3-triazole derivatives were synthesised using Huisgen 1,3-dipolar cyclo-addition reaction (click chemistry approach) and evaluated for their in vitro inhibition activity on concanavalin A (ConA) induced T cell proliferation and lipopolysaccharide (LPS) induced B cell proliferation. Among the synthesised series, compounds 2-10 and 19 exhibited significant inhibition against ConA and LPS stimulated T-cell and B-cell proliferation in a dose dependent manner. More significantly compounds 4, 9-10 and 19 exhibited potent inhibition activity with remarkably lower cytotoxicity on the mitogen-induced T cell and B cell proliferation at 1 MUM concentration. The compound 6 displayed potent immunosuppressive effects with ~89% against LPS induced B-cell and ~83% against ConA stimulated T-cell proliferation at 100 MUM concentration without cytotoxicity. Compound 10 was more selective against B cell proliferation and exhibited 81% and 69% suppression at 100 and 1 MUM concentration respectively. The present study led to the identification of several santonin analogs with reduced cytotoxicity and strong inhibition activity against the cell proliferation induced by the mitogens. PMID- 27191614 TI - The therapeutic voyage of pyrazole and its analogs: A review. AB - Pyrazole, a five membered heteroaromatic ring with two nitrogen atoms is of immense significance. Presence of this nucleus in the pharmacological agents of diverse therapeutic categories viz. antianxiety, anti-inflammatory, antipsychotic, anticancer, antiobesity, analgesic, antipyretic etc. has made it an indispensable anchor for design and development of new pharmacological agents. Owing to the development of novel and new pyrazole based therapeutic agents at a faster pace, there is a need to couple the latest information with previously available information to understand status of this moiety in medicinal chemistry research. The review herein highlights the therapeutic worth of pyrazole derivatives. Several therapeutically active pyrazole based derivatives developed by numerous scientists across the globe are reported here. PMID- 27191615 TI - 2,3,4-Trihydroxybenzyl-hydrazide analogues as novel potent coxsackievirus B3 3C protease inhibitors. AB - Human coxsackievirus B3 (CVB3) 3C protease plays an essential role in the viral replication of CVB3, which is a non-enveloped and positive single-stranded RNA virus belonging to Picornaviridae family, causing acute viral myocarditis mainly in children. During optimization based on SAR studies of benserazide (3), which was reported as a novel anti-CVB3 3C(pro) agent from a screening of compound libraries, the 2,3,4-trihydroxybenzyl moiety of 3 was identified as a key pharmacophore for inhibitory activity against CVB3 3C(pro). Further optimization was performed by the introduction of various aryl-alkyl substituted hydrazide moieties instead of the serine moiety of 3. Among the optimized compounds, 11Q, a 4-hydroxyphenylpentanehydrazide derivative, showed the most potent inhibitory activity (IC50 = 0.07 MUM). Enzyme kinetics studies indicated that 11Q exhibited a mixed inhibitory mechanism of action. The antiviral activity against CVB3 was confirmed using the further derived analogue (14b) with more cell permeable valeryl ester group at the 2,3,4-trihydroxy moiety. PMID- 27191616 TI - Gold(III) complexes with ONS-Tridentate thiosemicarbazones: Toward selective trypanocidal drugs. AB - Tridentate thiosemicarbazone ligands with an ONS donor set, H2L(R) (R = Me and Et) were prepared by reactions of 1-phenyl-1,3-butanedione with 4-R-3 thiosemicarbazides. H2L(R) reacts with Na[AuCl4].2H2O in MeOH in a 1:1 M ratio under formation of green gold(III) complexes of composition [AuCl(L(R))]. These compounds represent the first examples of gold(III) complexes with ONS chelate bonded thiosemicarbazones. The in vitro anti-Trypanosoma cruzi activity against both trypomastigote and amastigote forms (IC50try/ama) of CL Brener strains as well as the cytotoxicity against LLC-MK2 cells of the free ligands and complexes was evaluated. The complex [AuCl(L(Me))] was found to be more active and more selective than its precursor ligand and the standard drug benznidazole with a SItry/ama value higher than 200, being considered as a lead candidate for Chagas disease treatment. Moreover the in vitro activity against the replicative amastigote form (IC50ama) of T. cruzi was additionally investigated revealing that [AuCl(L(Me))] was also more potent than benznidazole still with a similar selectivity index. Finally, docking studies showed that free ligands and complexes interact with the same residues of the parasite protease cruzain but with different intensities, suggesting that this protease could be a possible target for the trypanocidal action of the obtained compounds. PMID- 27191618 TI - Design, synthesis and antifungal activity of novel furancarboxamide derivatives. AB - Twenty-seven novel furancarboxamide derivatives with a diphenyl ether moiety were synthesized and evaluated for their antifungal activity against Rhizoctonia solani, Botrytis cirerea, Valsa mali and Sphaceloma ampelimum. Antifungal bioassay results indicated that most compounds had good or excellent fungicidal activities for R. solani and S. ampelimum at 20 mg L(-1). Among synthesized compounds, compound 18e showed a greater inhibitory effect against S. ampelimum, with half maximal effective concentration (EC50) values of 0.020 mg L(-1). This strong activity rivals currently used commercial fungicides, such as Boscalid and Carbendazim, and has great potential as a lead compound for future development of novel fungicides. PMID- 27191617 TI - 3-(Benzodioxan-2-ylmethoxy)-2,6-difluorobenzamides bearing hydrophobic substituents at the 7-position of the benzodioxane nucleus potently inhibit methicillin-resistant Sa and Mtb cell division. AB - Lipophilic substituents at benzodioxane C (7) of 3-(benzodioxan-2-ylmethoxy)-2,6 difluorobenzamide improve the antibacterial activity against methicillin resistant Staphylococcus aureus strains to MIC values in the range of 0.2-2.5 MUg/mL, whereas hydrophilic substituents at the same position and modifications at the benzodioxane substructure, excepting for replacement with 2-cromanyl, are deleterious. Some of the lead compounds also exhibit good activity against Mtb. Parallel SARs to those of 3-(2-benzothiazol-2-ylmethoxy)-2,6-difluorobenzamide, well known FtsZ inhibitor, and cells alterations typical of FtsZ inhibition indicate such a protein as the target of these potent antibacterial benzodioxane benzamides. PMID- 27191619 TI - 8-Hydroxyquinolines in medicinal chemistry: A structural perspective. AB - 8-Hydroxyquinolines are heterocyclic compounds characterized by a moderate metal binding affinity. The interest in 8-hydroxyquinolines has grown exponentially in the last two decades as they are privileged structures for the design of new drug candidates that exert a host of biological effects on various targets. The study of biological activities such as neuroprotection, anticancer, antibacterial, antifungal activity has been further promoted by the synthetic versatility of 8 hydroxyquinoline, which allows the generation of a large number of derivatives. These include numerous multifunctional analogues having the metal-binding motif of 8-hydroxyquinoline. In this review, we have summarized 8-hydroxyquinolines, 8 hydroxyquinoline-like compounds, 8-hydroxyquinoline-loaded nanoparticle systems with respect to their biological activities, interaction with metal ions and mechanisms of action. PMID- 27191620 TI - Association of Sleep Disordered Breathing with Mono-Symptomatic Nocturnal Enuresis: A Study among School Children of Central India. AB - OBJECTIVE: To study the prevalence of primary monosymptopomatic nocturnal enuresis (PMNE) in children aged 5-10 year and to find its association with sleep disordered breathing (SDB) by using a 22 item pediatric sleep related breathing disorder (SRBD) scale. METHODS: This was a school based cross sectional epidemiological study from July 2015 to November 2015. A questionnaire seeking information on socio-demographic variables, nocturnal enuresis (NE) frequency, school performance and a validated 22 item pediatric sleep related breathing disorder scale (SRBDs) was distributed to 1820 pupils in three primary schools. RESULTS: A total of 1528(83.95%) questionnaires were retrieved. Out of 1528 forms, 182(11.9%) forms were incomplete for requested information and hence 1346 (73.9%) questionnaires were finally analyzed. The prevalence of NE was found to be 12.7% (95% CI; 11-14.6), whereas prevalence of primary nocturnal enuresis (PMNE) was 8.2% (95% CI; 7.1-10.1). SRBD scale score >0.33 (adjusted OR: 2.87; 95%CI: 1.67-4.92), paternal history of enuresis in childhood (adjusted OR:4.96; 95% CI: 2.36-10.45), and inappropriate toilet training (adjusted OR: 1.64; 95% CI: 1.01-2.66) were independently associated with PMNE. CONCLUSION: Sleep disordered breathing, inappropriate toilet training and a history of childhood NE in father were found to be significant risk factors for PMNE in the present study. Thus, these findings suggest that it is imperative to rule out SDB in PMNE patients as they may require different therapeutic interventions. PMID- 27191622 TI - Ptosis Repair in Ocular Myasthenia Gravis. AB - Ptosis repair was performed in patients with ocular myasthenia gravis by a posterior approach (Fasanella-Servat, 12 eyelids of nine patients) or levator advancement (eight eyelids of five patients) techniques. There were eight males and five females. Median age was 73 years and range 30-86 years. The median duration of myasthenia was 10 years and range 2 to 28 years. Pyridostigmine and prednisone were widely used prior to surgical referral, but ineffective or intolerable in all. The mean preoperative upper margin-reflex distance (MRD) was 0.55 mm (range -1 to 2 mm). The levator excursion range was 10 to 16 mm and mean 12.4 mm. Mean follow-up was 9.1 months. Postoperatively, the MRD ranged from 0.5 to 4 mm, with a mean of 2.3 mm. Two patients had lagophthalmos postoperatively (one posterior approach, one levator advancement) that did not require correction. Three of five patients who underwent levator advancement required repeat ptosis repair. PMID- 27191621 TI - Post-Ebola Measles Outbreak in Lola, Guinea, January-June 2015(1). AB - During public health crises such as the recent outbreaks of Ebola virus disease in West Africa, breakdowns in public health systems can lead to epidemics of vaccine-preventable diseases. We report here on an outbreak of measles in the prefecture of Lola, Guinea, which started in January 2015. PMID- 27191623 TI - Synthesis of substituted phenylcarbamates of N-cyclobutylformylated chitosan and their application as chiral selectors in enantioseparation. AB - The goal of this study was to develop new chiral stationary phases (CSPs) with high chiral recognition capability and high compatibility with the so-called "nonstandard solvents". Seven new chitosan bis(phenylcarbamate)-(N cyclobutylformamide) derivatives were synthesized from chitosan with high degree of deacetylation as a starting material. The corresponding chiral stationary phases (CSPs 1-7) were prepared with the chitosan derivatives as chiral selectors (CSs). The enantioseparation capability of CSPs 1-7 was evaluated by high performance liquid chromatography with nineteen analytes. In comparison with the CSPs of cellulose tris(3,5-dimethylphenylcarbamate) (CDMPC) and amylose tris(3,5 dimethylphenylcarbamate) (ADMPC), the prepared CSPs generally demonstrated excellent enantioseparation capability, particularly for the CSP derived from chitosan bis(3-chloro-4-methylphenylcarbamate)-(N-cyclobutylformamide). Moreover, the CSPs in the present study could separate some analytes better, making them complementary for enantioseparations with the CSPs of CDMPC and ADMPC. The tolerability of the CSP with the best enantioseparation capability to organic solvents was investigated. The results showed that it could work in pure ethyl acetate, pure chloroform, and a normal phase containing 70% tetrahydrofuran, which are prevented from enantioseparation by the coating type CSPs of CDMPC and ADMPC. As these chitosan derivatives were almost insoluble in most organic solvents, the corresponding CSPs can work in a wide range of mobile phases. In addition, the influence of the position and electron effects of methyl and chloro groups introduced onto the CSs and the composition of mobile phases on enantioseparation was also discussed. PMID- 27191624 TI - Ultrasound-Assisted Solvent-Free Parallel Synthesis of 3-Arylcoumarins Using N Acylbenzotriazoles. AB - An ultrasound-assisted one-pot acylation/cyclization reaction between N acylbenzotriazoles and 2-hydroxybenzaldehydes has been developed for the synthesis of substituted 3-arylcoumarins. Using ultrasound not only allows rapid and clean conversion but also simplifies experimental setup and parallel workup leading to rapid generation of 3-arylcoumarin libraries under mild, solvent-free, and chromatography-free conditions. PMID- 27191625 TI - Aortic Centers of Excellence: Shifting the Focus. PMID- 27191626 TI - Choroidal Thinning May Change Scleral Architecture. PMID- 27191628 TI - The Professors Rate Us. PMID- 27191627 TI - Development of a Computer-Based Format for the Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST) With University Students. AB - BACKGROUND: The Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST) is a reliable and valid tool for the early detection of harmful and hazardous drug use in primary care settings when administered by interview in the general population. In university students, substance use is high, so a reliable and feasible screening instrument is needed. OBJECTIVES: To compare the computer based ASSIST (ASSISTc) with the interview format (ASSISTi). METHODS: A convenience sample with counterbalanced design was used alternating between the ASSISTi and ASSISTc with 15-day interval. Although this is not a traditional test retest reliability study, the same statistical analysis was used: intraclass correlations (ICC), kappa (kappa), and Cronbach's alpha (alpha) to compare the two formats. A satisfaction questionnaire was applied immediately after the second session. RESULTS: Both formats were completed by the students (n = 809) over 15 days. The scores of involvement with all substances and with tobacco, alcohol, cannabis, and cocaine obtained with the two formats demonstrated excellent ICC (> .77). The level of agreement was considered substantial for tobacco (kappa = .69) and cannabis (kappa = .70) and moderate for alcohol (kappa = .58). The consistency of the ASSISTc was considered satisfactory (alpha: .85 for tobacco, .73 for alcohol, and .87 for cannabis). The analysis of satisfaction and feasibility showed that the ASSISTi was easier to understand, but the two formats were considered similar when considering acceptability, ease of responding, and degree of intimidation. CONCLUSIONS/IMPORTANCE: The two formats are acceptable, the scores are comparable, and they can be used interchangeably. PMID- 27191629 TI - Problems+Solutions. AB - Readers are invited to submit questions relating to problem cases. Inquiries will be answered by qualified consultants and replies forwarded by mail promptly. Selected problems and solutions are published every month in this section. PMID- 27191630 TI - The Medical Bookshelf. AB - Books received are listed as space permits, and those of particular interest to our readers are reviewed. PMID- 27191631 TI - Jarm-don't jog-to live longer. AB - This section is reserved for commentaries and brief essays dealing with matters of interest to physicians. Material for consideration should not exceed five double-spaced typewritten pages. An honorarium of $75 is offered at the time of publication. Submissions should be addressed to: Editor, Postgraduate Medicine, 4530 W 77th St, Minneapolis. MN 55435. PMID- 27191633 TI - Trauma injuries. PMID- 27191632 TI - Trauma. PMID- 27191636 TI - Primary Care Digest. PMID- 27191634 TI - Cues/Tips. PMID- 27191638 TI - Developing interprofessional communication skills for pharmacists to improve their ability to collaborate with other professions. AB - Successful communication between health professionals is a prerequisite for collaborative practice. Clinical pharmacists completed a learning and practice module introducing them to a framework for successful interprofessional communication (IPC) in the course of their postgraduate studies. A face-to-face discussion of a contemporary clinical topic with a health professional was then scheduled, mainly with junior doctors, in their practice setting. An exploratory case study methodology was employed to investigate pharmacists' written reflections on their experience applying their newly acquired IPC skills. Thematic analysis of reflections developed five categories relating to interprofessional collaboration, learning, and education. Themes describing pharmacists' preconceptions about the health professional and scheduled interprofessional encounter, how it allowed them to learn about doctors' and other health professionals' practice and build collaborative relationships were identified. Reflections also elaborated that applying the communication framework and strengthening of collaboration created opportunities for IPE, with added observations about these increasing potential impact on patient care and change of practice. Analysis of anonymous feedback provided by the health professionals yielded similar themes and was integrated for triangulation. Applying successful IPC skills in healthcare settings may increase interprofessional collaboration and create practice models which facilitate interprofessional learning in health profession programmes. PMID- 27191639 TI - Lighting the way. PMID- 27191640 TI - Designing convergent chemistry curricula. PMID- 27191641 TI - Gene expression: Means to an end. PMID- 27191642 TI - Genomics: A Tribe for RNA. PMID- 27191643 TI - Protein evolution: Polymerase's new language. PMID- 27191645 TI - Proteostasis: Chaperoning for hearing loss. PMID- 27191646 TI - Cancer metabolism: Addicted to serine. PMID- 27191648 TI - Erratum: Chemoproteomic profiling of host and pathogen enzymes active in cholera. PMID- 27191647 TI - Metalloproteins: Mapping elusive electron density. PMID- 27191649 TI - Possible Transmission of mcr-1-Harboring Escherichia coli between Companion Animals and Human. PMID- 27191650 TI - Speed of leukemia development and genetic diversity in xenograft models of T cell acute lymphoblastic leukemia. AB - T cell acute lymphoblastic leukemia (T-ALL) develops through accumulation of multiple genomic alterations within T-cell progenitors resulting in clonal heterogeneity among leukemic cells. Human T-ALL xeno-transplantation in immunodeficient mice is a gold standard approach to study leukemia biology and we recently uncovered that the leukemia development is more or less rapid depending on T-ALL sample. The resulting human leukemia may arise through genetic selection and we previously showed that human T-ALL development in immune-deficient mice is significantly enhanced upon CD7+/CD34+ leukemic cell transplantations. Here we investigated the genetic characteristics of CD7+/CD34+ and CD7+/CD34- cells from newly diagnosed human T-ALL and correlated it to the speed of leukemia development. We observed that CD7+/CD34+ or CD7+/CD34- T-ALL cells that promote leukemia within a short-time period are genetically similar, as well as xenograft derived leukemia resulting from both cell fractions. In the case of delayed T-ALL growth CD7+/CD34+ or CD7+/CD34- cells were either genetically diverse, the resulting xenograft leukemia arising from different but branched subclones present in the original sample, or similar, indicating decreased fitness to mouse micro-environment. Altogether, our work provides new information relating the speed of leukemia development in xenografts to the genetic diversity of T-ALL cell compartments. PMID- 27191651 TI - Mesenchymal stem cells in combination with erythropoietin repair hyperoxia induced alveoli dysplasia injury in neonatal mice via inhibition of TGF-beta1 signaling. AB - The aim of the present study is to investigate the protection effects of bone marrow mesenchymal stem cells (MSCs) in combination with EPO against hyperoxia induced bronchopulmonary dysplasia (BPD) injury in neonatal mice. BPD model was prepared by continuous high oxygen exposure, 1*106 bone marrow MSCs and 5000U/kg recombinant human erythropoietin (EPO) were injected respectively. Results showed that administration of MSCs, EPO especially MSCs+EPO significant attenuated hyperoxia-induced lung damage with a decrease of fibrosis, radical alveolar counts and inhibition of the occurrence of epithelial-mesenchymal transition (EMT). Furthermore, MSCs+EPO co-treatment more significantly suppressed the levels of transforming growth factor-beta1(TGF-beta1) than MSCs or EPO alone. Collectively, these results suggested that MSCs, EPO in particular MSCs+EPO co treatment could promote lung repair in hyperoxia-induced alveoli dysplasia injury via inhibition of TGF-beta1 signaling pathway to further suppress EMT process and may be a promising therapeutic strategy. PMID- 27191652 TI - Expression of PD-1 on CD4+ T cells in peripheral blood associates with poor clinical outcome in non-small cell lung cancer. AB - Recent success of using agents inhibiting the major immune check point, programmed cell death-1 (PD-1) pathway, offers a great promise for effective cancer therapy. Two blocking antibodies for PD-1, nivolumab and pembrolizumab have recently been approved for treating advanced recurrent non-small cell lung cancer (NSCLC). Activation of PD-1 on T cells and PD-L1 on tumor cells or antigen presenting cells leads to T cell exhaustion and ultimately tumor growth. In this study, we performed flow cytometry analysis of peripheral blood samples collected from patients with advanced NSCLC at initial diagnosis. We report that surface expression of PD-1 on CD4+ T cells has a prognostic value in NSCLC patients, as high expression of PD-1 is associated with a shorter progression-free survival and overall survival. Importantly, we also found that high PD-1 expression on peripheral CD4+ T cells is associated with inferior clinical response in a subset of patients who received anti-PD-L1 treatment, indicating a potential predictive value of this marker. This work highlights the potential of a non-invasive and effective method to determine prognostic and predictive biomarkers for inhibiting the PD-1 pathway in NSCLC patients. PMID- 27191653 TI - Altered glutamine metabolism in platinum resistant ovarian cancer. AB - Ovarian cancer is characterized by an increase in cellular energy metabolism, which is predominantly satisfied by glucose and glutamine. Targeting metabolic pathways is an attractive approach to enhance the therapeutic effectiveness and to potentially overcome drug resistance in ovarian cancer. In platinum-sensitive ovarian cancer cell lines the metabolism of both, glucose and glutamine was initially up-regulated in response to platinum treatment. In contrast, platinum resistant cells revealed a significant dependency on the presence of glutamine, with an upregulated expression of glutamine transporter ASCT2 and glutaminase. This resulted in a higher oxygen consumption rate compared to platinum-sensitive cell lines reflecting the increased dependency of glutamine utilization through the tricarboxylic acid cycle. The important role of glutamine metabolism was confirmed by stable overexpression of glutaminase, which conferred platinum resistance. Conversely, shRNA knockdown of glutaminase in platinum resistant cells resulted in re-sensitization to platinum treatment. Importantly, combining the glutaminase inhibitor BPTES with platinum synergistically inhibited platinum sensitive and resistant ovarian cancers in vitro. Apoptotic induction was significantly increased using platinum together with BPTES compared to either treatment alone. Our findings suggest that targeting glutamine metabolism together with platinum based chemotherapy offers a potential treatment strategy particularly in drug resistant ovarian cancer. PMID- 27191654 TI - Long-term clinical outcome in nasopharyngeal carcinoma patients with post radiation persistently detectable plasma EBV DNA. AB - PURPOSE: To investigate the long-term clinical outcome of nasopharyngeal carcinoma (NPC) patients with persistently detectable plasma EBV (pEBV) DNA after curative radiotherapy (RT). RESULTS: The post-RT pEBV DNA levels were very lower copy number (median 21, interquartile range 8-206 copies/ml). After long-term follow-up, the relapse rate was 64.8%, the median time to progression 20 months, and 5-year overall survival (OS) 49.6%. Thirty-two of 39 (82.1%) patients with high viral load (>= 100 copies/ ml) developed tumor relapse, whereas 57.0% (49/86) patients with low viral load (< 100 copies/ml) had tumor relapse (P = 0.0065). The 5-year OS rates were 20.5% and 62.9% for patients with viral load >= and < 100 copies/ml (median survival, 20 vs. 100 months; P < 0.0001). Patients who received adjuvant chemotherapy (AdjCT) experienced significant reduction in distant failures (66.2% vs. 31.6%; P = 0.0001) but similar locoregional recurrences (P = 0.2337). The 5-year OS rates were 69.4% for patients who received AdjCT compared with 33.2% for those of without AdjCT (median survival, 111 vs. 32 months; P < 0.0001). METHODS: We screened 931 newly diagnosed NPC patients who finished curative RT and found 125 patients (13.4%) with detectable pEBV DNA one week after RT. The clinical characteristics, treatment modality, subsequent failure patterns and survivals were analyzed. CONCLUSIONS: NPC patients with persistently detectable pEBV DNA after curative RT have a higher rate of treatment failure and poor survivals. Levels of the post-RT pEBV DNA and administration of AdjCT affect the final outcome significantly. PMID- 27191657 TI - An Update on the Clinical Utility of the Children's Post-Traumatic Cognitions Inventory. AB - The Children's Post-Traumatic Cognitions Inventory (CPTCI) is a self-report questionnaire that measures maladaptive cognitions in children and young people following exposure to trauma. In this study, the psychometric properties of the CPTCI were examined in further detail with the objective of furthering its utility as a clinical tool. Specifically, we investigated the CPTCI's discriminant validity, test-retest reliability, and the potential for the development of a short form of the measure. Three samples (London, East Anglia, Australia) of children and young people exposed to trauma (N = 535; 7-17 years old) completed the CPTCI and a structured clinical interview to measure posttraumatic stress disorder (PTSD) symptoms between 1 and 6 months following trauma. Test-retest reliability was investigated in a subsample of 203 cases. The results showed that a score in the range of 46 to 48 on the CPTCI was indicative of clinically significant appraisals as determined by the presence of PTSD. The measure also had moderate-to-high test-retest reliability (r = .78) over a 2 month period. The Children's Post-Traumatic Cognitions Inventory-Short Form (CPTCI-S) had excellent internal consistency (alpha = .92), and moderate-to-high test-retest reliability (r = .78). The examination of construct validity showed the model had an excellent fitting factor structure (Comparative Fit index = 0.95, Tucker-Lewis index = 0.91, Root Mean Square Error of Approximation = .07). A score ranging from 16 to 18 was the best cutoff point on the CPTCI-S, in that it was indicative of clinically significant appraisals as determined by the presence of PTSD. Based on these results, we concluded that the CPTCI is a useful tool to support the practice of clinicians and that the CPTCI-S has excellent psychometric properties. PMID- 27191655 TI - rs965513 polymorphism as a common risk marker is associated with papillary thyroid cancer. AB - Papillary thyroid cancer (PTC) is the most common type of thyroid cancer. With the rapid development of genome-wide association studies (GWAS), many genome variants associated with susceptibility to PTC have been identified, including the single nucleotide polymorphism rs965513 (9q22.33) near FOXE1. To evaluate the association between rs965513 and PTC in different ethnicities and countries, we conducted a meta-analysis using relatively large-scale samples from 23 studies (N = 163,136; 20,736 cases and 142,400 controls) by searching the PubMed and Google Scholar databases. Significant heterogeneity caused by different populations among the selected studies was observed. The A allele of rs965513 polymorphism was shown to be highly associated with risk of thyroid cancer, with odds ratios of 1.58 (95% CI 1.32-1.90) in all populations, 1.65 (95% CI 1.31-2.07)) in Caucasian populations and 1.49 in Asian populations. Compared to the dominant and recessive models, we observed the highest odds ratio (OR = 2.80, 95% CI 2.12 3.69) in the homozygous model. These results revealed that the rs965513 polymorphism is a risk factor for thyroid cancer. PMID- 27191658 TI - Abstracts of the meeting of the Belgian Society of Internal Medicine (27 February 1988). PMID- 27191660 TI - Interrater reliability of electrodiagnosis in neonatal brachial plexopathy. AB - INTRODUCTION: We investigated interrater reliability of overall assessment of nerve root lesions by electrodiagnostic testing (EDX) in neonatal brachial plexus palsy (NBPP). METHODS: Two blinded, board-certified reviewers retrospectively reviewed de-identified EDX data from 37 infants with NBPP for 2005-2012. Only nerve conduction and electromyography needle data were included. The examiners independently assigned 1 of 4 nerve root lesion categories: (1) pre-ganglionic lesion (avulsion), (2) post-ganglionic lesion (rupture), (3) normal, or (4) "unable to determine." Simple percentage agreement, the Cohen kappa statistic representing interrater reliability for each nerve root (C5-T1), and overall kappa between examiners were evaluated. RESULTS: Interrater reliabilities were substantial to almost perfect for each nerve root except C5. Considering all nerve roots, overall interrater reliability was substantial (kappa = 0.62); simple percentage agreement was 75% (138/185). CONCLUSIONS: Interrater reliability of nerve root assessment by EDX for infants with NBPP was high for C6 T1 root levels, but less reliable for C5 because of technical factors. Muscle Nerve 55: 69-73, 2017. PMID- 27191656 TI - Isolation, identification, and characterization of novel nanovesicles. AB - Extracellular microvesicles (EVs) have been recognized for many potential clinical applications including biomarkers for disease diagnosis. In this study, we identified a major population of EVs by simply screening fluid samples with a nanosizer. Unlike other EVs, this extracellular nanovesicle (named HG-NV, HG-NV stands for HomoGenous nanovesicle as well as for Huang-Ge- nanovesicle) can be detected with a nanosizer with minimal in vitro manipulation and are much more homogenous in size (8-12 nm) than other EVs. A simple filtration platform is capable of separating HG-NVs from peripheral blood or cell culture supernatants. In comparison with corresponding exosome profiles, HG-NVs released from both mouse and human breast tumor cells are enriched with RNAs. Tumor derived HG-NVs are more potent in promoting tumor progression than exosomes. In summary, we identified a major subset of EVs as a previously unrecognized nanovesicle. Tumor cell derived HG-NVs promote tumor progression. Molecules predominantly present in breast tumor HG-NVs have been identified and characterized. This discovery may have implications in advancing both microvesicle biology research and clinical management including potential used as a biomarker. PMID- 27191661 TI - Novel insights into enhanced dewatering of waste activated sludge based on the durable and efficacious radical generating. AB - : This study aims to develop a high-efficiency radical oxidation process for enhancing the dewaterability of waste activated sludge (WAS). Radical scavenging studies combined with electron paramagnetic resonance (EPR) were carried out for the direct radical identification and effectiveness evaluation of radical oxidation. The results indicated that Fe(II)-activated CaO2 can pose a superior effect on dewatering WAS due to its distinctive capacity of stable *OH production and the high reaction efficiency of regulated-released *OH with water-holding organics. The mechanism for the enhanced dewatering performance was also explored. The rupture of sludge colloidal flocs and the reduction of hydrophilic functional groups in loosely bound extracellular polymeric substances (LB-EPS) were found to be mainly responsible for the release of interstitial water and improved dewaterability, respectively. In addition, an inference about the relationship between interfacial water and zeta potential of different EPS fractions was established by the simultaneous measurement of the binding affinities of Ca2+ and Fe2+/Fe3+ for EPS and bound water content. All these results provide the direct evidence that Fe(II)-activated CaO2 is a promising pretreatment reagent for sludge disposal. IMPLICATIONS: Fe(II)-activated CaO2 was first proposed to be highly effective in enhancing the dewaterability of waste activated sludge. Electron paramagnetic resonance (EPR) spectroscopy provided the direct evidence for the specific advantages of CaO2, especially the capacity of durable and efficacious *OH production leading to the excellent conditioning performance. PMID- 27191662 TI - Low-dose versus high-dose heparin locks for hemodialysis catheters: a systematic review and meta-analysis. AB - BACKGROUND: Low-dose heparin lock has been suggested as an effective and safe catheter lock in hemodialysis. However, whether a low-dose lock is superior to a high-dose heparin lock in preventing catheter-related infections and maintaining catheter patency is inconclusive. STUDY DESIGN: A systematic review and meta analysis was performed by searching in NGC (National Guideline Clearinghouse), Cochrane Library, Joanna Briggs Institute Library, MEDLINE, EMbase, RNAO (Registered Nurses' Association of Ontario), Nursing Consult, PubMed, OVID, China Biology Medicine disc (CBMdisc), China National Knowledge Infrastructure (CNKI), Chongqing VIP (CQVIP), Wanfang Data Knowledge Service Platform, and major nephrology journals. SETTING AND POPULATION: Patients receiving hemodialysis with central venous catheters. SELECTION CRITERIA FOR STUDIES: Randomized controlled trials (RCT), controlled clinical trials (CCT), and cohort studies comparing low dose heparin lock with high-dose heparin lock in hemodialysis patients with central venous catheters. Intervention (exposure): Locking central venous catheters with low-dose heparin lock. OUTCOMES: Primary outcomes include bleeding related complications and catheter-related infections. Secondary outcomes include catheter retention time, catheter thrombosis/occlusion incidence, and catheter dysfunction. RESULTS: Five RCTs and three CCTs were eventually identified for the meta-analysis, with 916 patients in total. Meta-analysis showed that, compared with the high-dose heparin group (>= 5,000 U/mL), the low-dose (< 5,000 U/mL) heparin lock could significantly reduce the incidences of bleeding- related complications RR = 3.29, 95% CI (2.19, 4.94), p < 0.00001) and catheterrelated infections (RR = 1.66, 95% CI (1.01, 2.73), p = 0.04). However, no significant differences were observed in the catheter retention time MD = 9.32, 95% CI ( 6.70, 25.35), p = 0.25), catheter thrombosis/occlusion incidence (RR = 0.68, 95% CI (0.28, 1.65), p = 0.39), or catheter dysfunction (RR = 1.07, 95% CI (0.75, 1.53), p = 0.71) between the high- and low-dose heparin groups. CONCLUSION: Low dose heparin lock could decrease the incidences of catheter-related infections and bleeding-related complications without influencing the catheter retention time or the incidence of catheter thrombosis/occlusion or catheter dysfunction. Low-dose heparin lock solution should be recommended for the hemodialysis patients using central venous catheter in clinic. PMID- 27191663 TI - Serum phosphorus adds to value of serum parathyroid hormone for assessment of bone turnover in renal osteodystrophy. AB - It is well-established that parathyroid hormone (PTH) correlates with the level of bone turnover in patients with chronic kidney disease stage 5D (CKD-5D). Hyperphosphatemia is a well-established complication of end-stage renal disease and is usually attributed to dietary intake. This study evaluates the relationship between serum phosphorus levels and bone turnover in patients with CKD-5D. 93 patients with CKD-5D from the Kentucky Bone Registry who had sequentially undergone anterior iliac bone biopsies were reviewed. Undecalcified bone sections were qualitatively assessed for turnover and placed into a group with low turnover and a group with non-low (normal/high) turnover. Results of PTH and phosphorus concentrations in blood drawn at the time of biopsies were compared between the groups. PTH and phosphorus levels were significantly higher in the non-low turnover group compared to the low turnover group. Cutoff levels for PTH and phosphorus were tested for predictive power of bone turnover. Both PTH and phosphorus correlated with turnover. Adding serum phosphorus to serum PTH enhanced predictive power of PTH for low turnover. The vast majority of patients with serum phosphorus levels >= 6.0 mg/dL had non-low turnover, while the majority of those with low turnover had phosphorus values < 6.0 mg/dL. Classification and regression-tree analysis showed that elevated serum phosphorus (> 6.2 mg/dL) in patients with PTH < 440 pg/mL was helpful in diagnosing nonlow turnover in this range of PTH. In patients with PTH ranges of 440 - 814 pg/mL, serum phosphorus levels > 4.55 mg/dL ruled out low turnover bone disease. This suggests that not only dietary intake but also bone affects serum phosphorus levels. PMID- 27191664 TI - Challenges with Accruing a Study of Topical Opioid for Painful Malignant Wounds: Lessons Learned. PMID- 27191665 TI - Optimal therapy and prospects for new medicines in eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome). AB - INTRODUCTION: The prevalence of eosinophilic granulomatosis with polyangiitis (EGPA; previously known as Churg-Strauss syndrome) is lower than that of other antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV's), and only a few randomized controlled trials have been conducted for this rare disease. However, recent international efforts have helped delineate the best treatment approach. AREAS COVERED: At present, EGPA conventional therapy is by default similar to that of other AAVs. Limited, non-severe EGPA can initially be treated with glucocorticoids (GCs) alone. Patients with life-threatening manifestations and/or major organ involvement must receive a combination of GCs and an immunosuppressant, mainly cyclophosphamide. Remission can be achieved in >85% of patients with these first-line treatments, but vasculitis relapses occur in more than one-third of patients, and about 85% cannot stop GC treatment because of GC-dependent asthma and/or ENT manifestations. A few biologic agents, including rituximab or mepolizumab, are now under investigation after interesting preliminary results. Expert commentary: Treatment for EGPA still has several unmet needs. Several biologic agents are now under investigation in randomized controlled trials, but a few others should be considered soon. Their benefit should be demonstrated for devising more EGPA-tailored therapeutic strategies (ideally GC-free). PMID- 27191666 TI - Measures of health, fitness, and functional movement among firefighter recruits. AB - AIM: The purpose of this study was to examine the associations between various health and fitness measures and Functional Movement ScreenTM (FMSTM) scores among 78 firefighter recruits. METHODS: Relationships between FMSTM scores and age, body mass index (BMI), sit and reach (S&R) distance, estimated maximal aerobic capacity (VO2max), estimated one-repetition maximum squat (1RM-Squatmax), and plank endurance (%Plankmax) were examined. RESULTS: Total FMSTM scores were significantly correlated with BMI (r = -0.231, p = 0.042), estimated 1RM-Squatmax (r = 0.302, p = 0.007), and %Plankmax (r = 0.320, p = 0.004). Multiple regression analyses indicated that this combination of predictors significantly predicted (F(3, 74) = 5.043, p = 0.003) Total FMSTM score outcomes and accounted for 17% of the total variance (R2 = 0.170). In addition, logistic regression analyses indicated that estimated 1RM-Squatmax also significantly predicted (chi2 = 6.662, df = 1, p = 0.010) FMSTM group membership (<=14 or >=15). CONCLUSION: These results suggest that the health and fitness measures of obesity (BMI), bilateral lower extremity strength (estimated 1RM-Squatmax), and core muscular endurance (%Plankmax) are significantly associated with functional movement patterns among firefighter recruits. Consequently, injury prevention programs implemented among firefighter recruits should target these aspects of health and fitness. PMID- 27191667 TI - Corneal Astigmatism Stability in Descemet Membrane Endothelial Keratoplasty for Fuchs Corneal Dystrophy. AB - PURPOSE: To calculate the magnitude and angle of the shift in corneal astigmatism associated with Descemet membrane endothelial keratoplasty (DMEK) surgery to determine the feasibility of concurrent astigmatism correction at the time of DMEK triple procedures. DESIGN: Retrospective study. METHODS: Forty-seven eyes that previously underwent the DMEK procedure for Fuchs endothelial corneal dystrophy and that had more than 1.0 diopter (D) of front corneal astigmatism preoperatively were identified. All DMEK surgeries used a clear corneal temporal incision of 3.2 mm. Surgically induced astigmatism (SIA) was evaluated 6 months postsurgery with vector analysis using Scheimpflug image reading. RESULTS: We did not find a difference between pre- and postoperative magnitude of front astigmatism (P = 0.88; paired t test). The magnitude of the SIA front surface was 0.77 +/- 0.63 D (range, 0.10-3.14 D). The centroid vector of the SIA front surface was 0.14 at 89.3 degrees . A hyperopic corneal power shift was noted in both the front surface by 0.26 +/- 0.74 D (range, 0.45-3.05 D) (P = 0.018; paired t test) and back surface by 0.56 +/- 0.55 D (range, 0.25-2.40 D) (P < 0.01; paired t test). CONCLUSIONS: DMEK surgery induces minimal amounts of corneal astigmatism that is a with-the-rule shift associated with a temporal clear corneal incision. The stability of these data from preop to postop supports the plausibility of incorporating astigmatism correction with the cautious use of toric intraocular lenses for patients with Fuchs corneal dystrophy and cataract. PMID- 27191668 TI - Descemet Membrane Endothelial Keratoplasty (DMEK) Tissue Preparation: A Donor Diabetes Mellitus Categorical Risk Stratification Scale for Assessing Tissue Suitability and Reducing Tissue Loss. AB - PURPOSE: This study assessed a novel diabetes mellitus (DM) rating scale in relation to its utility in reducing Descemet membrane endothelial keratoplasty (DMEK) tissue preparation failure. METHODS: A 5-point DM rating scale was defined, in which 1 demonstrated relatively good health associated with DM and 5 represented comorbidities associated with DM. A chart review from consecutive donors who had at least 1 tissue prepared for DMEK was performed. Using the donor profile, the first tissue processed from each donor was categorized according to the DM severity and if the tissue passed or failed the DMEK preparation. Failure rates per rating group were evaluated using logistic regression and odds of preparation failure. RESULTS: A total of 125 tissues prepared for DMEK were categorized based on the defined DM rating scale. Of these, 9 tissues were rated 1 (11.1% failure), 25 were rated 2 (0% failure), 31 were rated 3 (6.5% failure), 24 were rated 4 (16.7% failure), and 36 were rated 5 (30.6% failure). The odds ratios were significant for tissues rated as 5 and 3 (P < 0.05). No other rating categories were found to influence the odds of failure. A chi test comparing categories of low risk (1-3) and high risk (4-5) was also performed (P = 0.001). CONCLUSIONS: The DM rating scale does seem to stratify the risk of preparation failure associated with the severity of DM and associated comorbidities. Inclusion of some diabetic donors for the preparation of DMEK grafts may be warranted given proper screening of the donor history and application of the rating scale. PMID- 27191669 TI - Acute Corneal Hydrops Complicated by Microbial Keratitis: Case Series Reveals Poor Immediate and Long-Term Prognosis. AB - PURPOSE: Acute corneal hydrops is a rare complication of keratoconus and may be a risk factor for further complications such as microbial keratitis. METHODS: Retrospective, case series. RESULTS: Six eyes developed microbial keratitis during acute corneal hydrops. Risk factors for the development of microbial keratitis included epithelial defect, contact lens wear, trichiasis, and use of topical steroids. Two eyes developed corneal perforation and 1 eye was treated for possible endophthalmitis. All eyes developed marked scarring and neovascularization with final visual acuity of 20/200 or less. Three eyes received penetrating keratoplasty, and each experienced endothelial rejection with 1 eye developing graft failure. CONCLUSIONS: Microbial keratitis is a rare complication that may develop during acute corneal hydrops. The infection may rapidly appear and spread throughout the cornea and can lead to severe corneal scarring, neovascularization, and loss of vision and may prejudice subsequent keratoplasty. Prophylactic topical antibiotics should always be considered when treating acute corneal hydrops. PMID- 27191670 TI - Tear Matrix Metalloproteinases and Myeloperoxidase Levels in Patients With Boston Keratoprosthesis Type I. AB - PURPOSE: To investigate the tear levels of matrix metalloproteinases (MMPs), myeloperoxidase (MPO), and tissue inhibitor of metalloproteinase-1 in eyes after Boston keratoprosthesis type I (B-KPro) implantation and to correlate these markers with the established B-KPro prognostic categories. METHODS: Tear washes were collected from 40 patients (7 with autoimmune disease, 2 with chemical burn, and 31 with other noncicatrizing diagnoses). Tear levels of MMPs, MPO, and tissue inhibitor of metalloproteinase-1 were quantified using multianalyte bead-based enzyme-linked immunosorbent assays. The total MMP activity was determined using a fluorimetric assay. The analytes were compared to the underlying diagnosis and other clinical factors. RESULTS: The MMP-8, MMP-9, and MPO levels were markedly elevated in the eyes with B-KPro (80 +/- 31, 291 +/- 77, and 244 +/- 33 pg/MUg, respectively). Chemical burn was associated with significantly higher tear MMP-8 (474 +/- 376 pg/MUg) and MMP-9 levels (1300 +/- 635 pg/MUg) compared with noncicatrizing diseases (MMP-8: 41 +/- 15 pg/MUg, P = 0.02 and MMP-9: 196 +/- 57 pg/MUg, P = 0.02) and higher MMP-9 levels compared with autoimmune diseases (MMP 8: 96 +/- 65 pg/MUg, P = 0.21 and MMP-9: 306 +/- 196 pg/MUg, P = 0.04). Similar analyte levels were observed in the B-KPro eye and the contralateral non-B-KPro eye of patients with bilateral diseases. MMP-8, MMP-9, and total MMP activities correlated strongly with each other. CONCLUSIONS: In the eyes with B-KPro, tear MMP-8 and MMP-9 levels seem to be related to the underlying ocular surface pathology and not significantly influenced by the presence of the prosthesis. PMID- 27191671 TI - Wave Front-Guided Photorefractive Keratectomy Using a High-Resolution Aberrometer After Corneal Collagen Cross-Linking in Keratoconus. AB - PURPOSE: To evaluate the clinical outcomes of wave front-guided (WFG) photorefractive keratectomy (PRK) using a high-definition aberrometer in corneas with keratoconus at least 1 year after corneal collagen cross-linking (CXL). METHODS: Prospective uncontrolled interventional case series study including a total of 34 consecutive eyes of 25 patients with keratoconus previously treated with CXL. All cases underwent WFG PRK using the VISX STAR S4 IR excimer laser and the iDesign system. All eyes had keratoconus grade I or II according to the Amsler-Krumeich classification. Visual, refractive, and ocular aberrometric outcomes were evaluated during a 12-month follow-up. Astigmatic changes were analyzed with the Alpins vector method. RESULTS: A significant improvement was observed in the uncorrected and corrected distance visual acuities (P < 0.001). The mean efficacy and safety indices at 12 months postoperatively were 1.58 +/- 1.11 and 1.96 +/- 1.52, respectively. Manifest sphere and cylinder were reduced significantly (P < 0.001), with 76.5% of the eyes having a spherical equivalent within +/-1.00 D at 12 months postoperatively. The mean difference vector and magnitude of error were 1.06 +/- 0.92 and 0.43 +/- 0.86 D, respectively. Some corneal irregularity indices were reduced significantly with surgery (P <= 0.005) as well as the level of ocular higher order aberrations, primary coma, and trefoil (P < 0.001). CONCLUSIONS: Sequential WFG PRK using the iDesign system and the STAR S4 IR excimer laser after CXL is an effective option to correct the spherocylindrical error and to minimize the level of higher order aberrations in mild and moderate keratoconus if the maximum intended ablation depth does not exceed 15% of the minimal corneal thickness. PMID- 27191673 TI - Eckardt Keratoprosthesis for Tectonic Repair of a Large Corneal Perforation. AB - PURPOSE: To report on the use of the Eckardt keratoprosthesis as an emergency temporary tectonic seal for a full-thickness, large decentered corneal perforation. METHODS: Case report and review of the literature. RESULTS: A 47 year-old male patient with myotonic dystrophy presented with a large corneal perforation as a complication of chronic ulceration caused by lagophthalmia and recurrent herpetic keratitis. The perforation was triggered by a superinfection with Gram-positive bacteria. In an emergency setting where no donor cornea was available, the Eckardt keratoprosthesis was sutured into the debrided corneal defect as a tectonic measure. A secondary procedure, consisting of open sky cataract extraction combined with penetrating keratoplasty was performed 3 weeks later. During this period, the prosthesis was well tolerated and the anterior chamber stayed well formed. CONCLUSIONS: The Eckardt keratoprosthesis allowed us to convert what would have been an emergency a chaud keratoplasty into a well controlled elective procedure. In our case, the silicone prosthesis was well tolerated during the 3-week period while awaiting final repair with a corneal donor button. PMID- 27191672 TI - Corneoscleral Laceration and Ocular Burns Caused by Electronic Cigarette Explosions. AB - PURPOSE: To report cases of acute globe rupture and bilateral corneal burns from electronic cigarette (EC) explosions. METHODS: Case series. RESULTS: We describe a series of patients with corneal injury caused by EC explosions. Both patients suffered bilateral corneal burns and decreased visual acuity, and one patient sustained a unilateral corneoscleral laceration with prolapsed iris tissue and hyphema. A review of the scientific literature revealed no prior reported cases of ocular injury secondary to EC explosions; however, multiple media and government agency articles describe fires and explosions involving ECs, including at least 4 with ocular injuries. CONCLUSIONS: Given these cases and the number of recent media reports, ECs pose a significant public health risk. Users should be warned regarding the possibility of severe injury, including sight-threatening ocular injuries ranging from corneal burns to full-thickness corneoscleral laceration. PMID- 27191674 TI - Long-Term Density Changes in Corneal Layers After Primary Pterygium Excision With Topical Mitomycin-C. AB - PURPOSE: To evaluate the long-term change in average corneal densities at 18 months after primary pterygium excision with topical adjuvant mitomycin-C application, particularly the relationship between anterior and posterior corneal layer densities. METHODS: Prospective observational case series. Patients were imaged with the Pentacam at 18 months after their surgery. Average corneal densities were the primary outcome and were compared with postoperative weeks 1, 4, and 12 data using paired t test. RESULTS: In all, 31 eyes of 31 patients were recruited. Mean age at time of operation was 62.0 +/- 9.4 years. Mean best corrected logarithm of the minimal angle of resolution visual acuity at 18 months was 0.14. The mean total anterior, central, and posterior average corneal densities were 30.6, 25.9, and 20.5 respectively. Compared with postoperative week 1 data, the anterior layer was reduced by 12.7% (P = 0.0144); however, there was no significant change in the central and posterior layers (P = 0.5353 and 0.0858, respectively). Subgroup analyses did not support the use of a 10- to 12 mm annulus as opposed to total-diameter data, and density reduction effect at 18 months from week 12 and week 1 seemed to be stronger in males (P = 0.0074 and 0.0042, respectively). CONCLUSIONS: Anterior corneal scars continued to diminish in density with time. Previous finding of a significant increase in posterior layer density at postoperative week 12 is likely not a result of optical phenomenon caused by a less dense anterior layer. Sex difference in terms of scar remodeling may be present. PMID- 27191675 TI - Boston Type 1 Keratoprosthesis: Visual Outcomes, Device Retention, and Complications. AB - PURPOSE: To determine the visual outcomes, device retention, and complications after Boston type 1 keratoprosthesis (KPro-1) device implantation. METHODS: Comprehensive review of every case of KPro-1 implantation at a tertiary eye care center. RESULTS: The initial KPro-1 procedure, performed in 75 eyes without a previous keratoprosthesis, was included in the analysis. During the first 6 postoperative months, improvement occurred in the mean preoperative best corrected visual acuity of 20/1265 to a mean best-obtained postoperative visual acuity of 20/97 (P < 0.001). After a mean follow-up period of 41.4 months (range, 0.8-82.8 months), the final mean best-corrected visual acuity was 20/428. Improved vision was recorded in 43 eyes (57.3%), ambulatory vision (>=20/400) in 47 eyes (62.7%), intermediate functional vision (>=20/80) in 23 eyes (30.7%), and full functional vision (>=20/40) in 11 eyes (14.7%). The initial device was retained in 64 eyes (85.3%), with a Kaplan-Meier retention probability of 96% at 6 months and 82% at 5 years. One or more sight-threatening complications occurred in 51 eyes (68%). These included device extrusion in 11 eyes (14.7%), ulcerative keratitis in 12 eyes (16%), endophthalmitis in 7 eyes (9.3%), sterile vitritis in 3 eyes (4%), retroprosthetic membranes in 25 eyes (33.3%), maculopathy in 26 eyes (34.7%), retinal detachment in 9 eyes (12%), and progressive optic neuropathy in 7 eyes (9.3%). CONCLUSIONS: Boston KPro-1 implantation is associated with satisfactory visual outcomes and excellent device retention in a majority of cases. However, serious postoperative complications are common and may compromise the final visual result. PMID- 27191677 TI - Adjusting Local Molecular Environment for Giant Ambient Thermal Contraction. AB - A low-energy triggered switch that can generate mechanoresponse has great technological potential. A submolecular moiety, S-dibenzocyclooctadiene (DBCOD) that is composed of a flexible eight-membered ring connecting to a phenyl ring at each end, undergoes a conformational change from twist-boat to chair under a low energy stimulus such as near infrared irradiation, resulting in thermal contraction of DBCOD-based polymer. Experimental evidence corroborated by theoretical calculations indicates that introducing molecular asymmetry can reduce crystallinity significantly and consequently facilitate the kinetics of the conformational change. It has been demonstrated that the negative thermal expansion (NTE) coefficient of a DBCOD-based polymer system can be adjusted in a range from -1140 to -2350 ppm K-1 . -2350 ppm K-1 is ~10 times better than the value reported by the second best NTE system. PMID- 27191676 TI - Anti-Proliferation Effects of Garlic (Allium sativum L.) on the Progression of Benign Prostatic Hyperplasia. AB - Benign prostatic hyperplasia (BPH) is a urologic disease that affects most of men over the age 50. But until now there is no such perfect cure without side effects. Because of diverse adverse effects, it is desirable to develop effective and long term-safety-herbal medicines to inhibit the progress of BPH. In spite of garlic's large use and a wide spectrum of studies, including anti-hyperlipidemic, cardio-protective, and anti-inflammatory activities, there was none to prove efficacy for BPH. In this study, we evaluated the efficacy of garlic to prove its suppressing effects on BPH. Garlic administration decreased relative prostate weight ratio, suppressed mRNA expression level of AR, DHT serum levels, and the growth of prostatic tissue in BPH-induced rats. Moreover, garlic administration decreased the levels of inflammatory proteins, iNOS, and COX-2 in prostatic tissue. Further investigation showed that garlic induced accumulation of death inducing signal complex and activation of AMPK and decreased the levels of anti apoptotic proteins, such as Bcl-2, Bcl-xL, and survivin. These results suggest that garlic may have suppressing effects on BPH and it has great potential to be developed as treatment for BPH. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27191678 TI - 'Competent persons who can treat you with competence, as simple as that' - an interview study with transgender people on their experiences of meeting health care professionals. AB - AIMS AND OBJECTIVES: With a focus on sexual health and rights, this study describes how transgender people experience meetings with health care professionals. BACKGROUND: Transgender people face prejudice and discrimination worldwide. Little is known of their experiences in sexual health-promoting settings. METHOD: Within a descriptive design, 20 persons aged 18-74 and identifying as transgender and nonbinary were interviewed. The results were analysed with constructivist grounded theory. RESULTS: Disrespect among health care professionals is the core category connected to the experiences in the result; transgender people experience estrangement, expectations and eviction in different sexual health-promoting settings. CONCLUSION: Transgender knowledge needs to be increased in general, in both specialised transgender health care and many other health care settings, to prevent transgender peoples' experiences of estrangement. Moreover, an increased knowledge of, and respect for, sexual health and rights is needed to prevent transgender peoples' exposure to gender binary, cis- and heteronormative expectations. In addition, access to sexual health care is essential following gender-confirmatory care as well to avoid transgender peoples' experiences of eviction from the health care system. RELEVANCE TO CLINICAL PRACTICE: Nurses have an important role to play in striving for equity and justice within health care. This study describes how health care professionals appear to be disrespectful and suggestions of how this can be avoided are made. PMID- 27191680 TI - Improved chromatographic method for purification of lactoperoxidase from different milk sources. AB - Our previous studies showed that sulfanilamide is a new competitive inhibitor of and can be used in the purification of lactoperoxidase (LPO, EC1.11.1.7) from milk. However, this method has some disadvantages like a lower purification factor. The aim of the present study is to improve the purification process of milk LPO from different sources. For this purpose, 16 commercial sulfanilamide derivatives were selected for inhibition studies to determine the best inhibitor of bovine LPO by calculating kinetic parameters. A cyanogen bromide-activated Sepharose 4B affinity matrix was synthesized by coupling with each competitive inhibitor. Among the inhibitors, 5-amino-2-methylbenzenesulfonamide and 2-chloro 4-sulfamoylaniline were used as ligands for the purification of LPO from bovine, buffalo, cow, and goat milks with 1059.37, 509.09, 232.55, and 161.90, and 453.12 , 151.86-, 869.00-, and 447.57-fold, respectively. Our results show that 5-amino 2-methylbenzenesulfonamide, 2-chloro-4-sulfamoylaniline, and 5-amino-1 naphthalenesulfonamide are the best inhibitors for one-step purification of the enzyme. PMID- 27191679 TI - Anisotropically Stiff 3D Micropillar Niche Induces Extraordinary Cell Alignment and Elongation. AB - A microfabricated pillar substrate is developed to confine, align, and elongate cells, allowing decoupled analysis of stiffness and directionality in 3D. Mesenchymal stem cells and cardiomyocytes are successfully confined in a 3D environment with precisely tunable stiffness anisotropy. It is discovered that anisotropically stiff micropillar substrates provide cellular confinement in 3D, aligning cells in the stiffer direction with extraordinary elongation. PMID- 27191682 TI - Noble-Metal-Free Materials for Surface-Enhanced Raman Spectroscopy Detection. AB - Surface-enhanced Raman spectroscopy (SERS) is an attractive tool for the sensing of molecules in the fields of chemical and biochemical analysis as it enables the sensitive detection of molecular fingerprint information even at the single molecule level. In addition to traditional coinage metals in SERS analysis, recent research on noble-metal-free materials has also yielded highly sensitive SERS activity. This Minireview presents the recent development of noble-metal free materials as SERS substrates and their potential applications, especially semiconductors and emerging graphene-based nanostructures. Rather than providing an exhaustive review of this field, possible contributions from semiconductor substrates, characteristics of graphene enhanced Raman scattering, as well as effect factors such as surface plasmon resonance, structure and defects of the nanostructures that are considered essential for SERS activity are emphasized. The intention is to illustrate, through these examples, that the promise of noble metal-free materials for enhancing detection sensitivity can further fuel the development of SERS-related applications. PMID- 27191681 TI - Complete Series of {FeNO}(8), {FeNO}(7), and {FeNO}(6) Complexes Stabilized by a Tetracarbene Macrocycle. AB - Use of a macrocyclic tetracarbene ligand, which is topologically reminiscent of tetrapyrrole macrocycles though electronically distinct, has allowed for the isolation, X-ray crystallographic characterization and comprehensive spectroscopic investigation of a complete set of {FeNO}(x) complexes (x = 6, 7, 8). Electrochemical reduction, or chemical reduction with CoCp2, of the {FeNO}(7) complex 1 leads to the organometallic {FeNO}(8) species 2. Its crystallographic structure determination is the first for a nonheme iron nitroxyl {FeNO}(8) and has allowed to identify structural trends among the series of {FeNO}(x) complexes. Combined experimental data including (57)Fe Mossbauer, IR, UV-vis-NIR, NMR and Kbeta X-ray emission spectroscopies in concert with DFT calculations suggest a largely metal centered reduction of 1 to form the low spin (S = 0) {FeNO}(8) species 2. The very strong sigma-donor character of the tetracarbene ligand imparts unusual properties and spectroscopic signatures such as low (57)Fe Mossbauer isomer shifts and linear Fe-N-O units with high IR stretching frequencies for the NO ligand. The observed metal-centered reduction leads to distinct reactivity patterns of the {FeNO}(8) species. In contrast to literature reported {FeNO}(8) complexes, 2 does not undergo NO protonation under strictly anaerobic conditions. Only in the presence of both dioxygen and protons is rapid and clean oxidation to the {FeNO}(7) complex 1 observed. While 1 is stable toward dioxygen, its reaction with dioxygen under NO atmosphere forms the {FeNO}(6)(ONO) complex 3 that features an unusual O-nitrito ligand trans to the NO. 3 is a rare example of a nonheme octahedral {FeNO}(6) complex. Its electrochemical or chemical reduction triggers dissociation of the O-nitrito ligand and sequential formation of the {FeNO}(7) and {FeNO}(8) compounds 1 and 2. A consistent electronic structure picture has been derived for these unique organometallic variants of the key bioinorganic {FeNO}(x) functional units. PMID- 27191684 TI - Optimizing Stimulation in a Case of Facial Pain Through "Cross-Talk" of Peripheral and Central Leads: A Case Report. AB - OBJECTIVES: To describe inter-lead (cross-talk) stimulation between a trigeminal nerve lead and a cervical epidural lead for the treatment of facial pain in a 69 year-old patient with empty nose syndrome. MATERIALS AND METHODS: A trial implant was performed with a peripheral V2 trigeminal lead and a C1-C2 lead in cross-talk configuration. During permanent implant, the V2 lead was placed uneventfully while the central lead could only be advanced to C3-C4. RESULTS: During the trial, pain decreased by 70%. One month after permanent implant, the patient still experienced a 60-70% reduction in pain levels and a decrease from ten to two weekly pain episodes. Nine months post implant, the patient reported complete pain relief (0/10 on a numeric rating scale ranging from 0 to 10) and medications were discontinued. Infrequent exacerbations (3/10) were controlled by increasing stimulation. Three years post implant, the patient continued to have no baseline pain and could easily control exacerbations. CONCLUSION: Cross-talk configuration between a peripheral and a central lead created a more efficient stimulation technique. The resulting paresthesia was superior to that obtained from either lead alone and exceeded the paresthesia obtained from the combination of the two leads when used simultaneously, without an inter-lead configuration. PMID- 27191683 TI - Comparing the energy landscapes for native folding and aggregation of PrP. AB - Protein sequences are evolved to encode generally one folded structure, out of a nearly infinite array of possible folds. Underlying this code is a funneled free energy landscape that guides folding to the native conformation. Protein misfolding and aggregation are also a manifestation of free-energy landscapes. The detailed mechanisms of these processes are poorly understood, but often involve rare, transient species and a variety of different pathways. The inherent complexity of misfolding has hampered efforts to measure aggregation pathways and the underlying energy landscape, especially using traditional methods where ensemble averaging obscures important rare and transient events. We recently studied the misfolding and aggregation of prion protein by examining 2 monomers tethered in close proximity as a dimer, showing how the steps leading to the formation of a stable aggregated state can be resolved in the single-molecule limit and the underlying energy landscape thereby reconstructed. This approach allows a more quantitative comparison of native folding versus misfolding, including fundamental differences in the dynamics for misfolding. By identifying key steps and interactions leading to misfolding, it should help to identify potential drug targets. Here we describe the importance of characterizing free energy landscapes for aggregation and the challenges involved in doing so, and we discuss how single-molecule studies can help test proposed structural models for PrP aggregates. PMID- 27191686 TI - Multi-Case Review of the Application of the Precautionary Principle in European Union Law and Case Law. AB - The precautionary principle was formulated to provide a basis for political action to protect the environment from potentially severe or irreversible harm in circumstances of scientific uncertainty that prevent a full risk or cost-benefit analysis. It underpins environmental law in the European Union and has been extended to include public health and consumer safety. The aim of this study was to examine how the precautionary principle has been interpreted and subsequently applied in practice, whether these applications were consistent, and whether they followed the guidance from the Commission. A review of the literature was used to develop a framework for analysis, based on three attributes: severity of potential harm, standard of evidence (or degree of uncertainty), and nature of the regulatory action. This was used to examine 15 pieces of legislation or judicial decisions. The decision whether or not to apply the precautionary principle appears to be poorly defined, with ambiguities inherent in determining what level of uncertainty and significance of hazard justifies invoking it. The cases reviewed suggest that the Commission's guidance was not followed consistently in forming legislation, although judicial decisions tended to be more consistent and to follow the guidance by requiring plausible evidence of potential hazard in order to invoke precaution. PMID- 27191685 TI - Intravitreal Dexamethasone Implant for the Treatment of Macular Edema in Chronic Non-infectious Uveitis. AB - PURPOSE: To report observations on the single and repeat use of the dexamethasone (DEX) intravitreal implant (Ozurdex; Allergan, Inc, Irvine, CA) for the treatment of macular edema in patients with non-infectious posterior segment uveitis. METHODS: A chart review of 15 consecutive patients (25 eyes) was conducted. The primary outcome measure of the first and subsequent implants was central retinal thickness (CRT) on spectral-domain optical coherence tomography (sdOCT). Secondary outcomes were best-corrected visual acuity (BCVA), time to repeat implant, and adverse events. Multilevel mixed-effects linear regression was used to determine the effect of the DEX implant compared with baseline. The Kaplan Meier estimator was used to examine survival from relapse. RESULTS: A total of 35 implants on 25 eyes of 15 patients were included in the analysis. Of these, 91.4% (32 of 35 eyes) had a reduction in CRT and 80% (20 of 25 eyes) had improved BCVA. After the first DEX implant, CRT decreased from 590 um (SE: 28 um) at baseline to 370 um (SE: 31 um) at 3 months (p < 0.001). The logMAR VA was 0.614 (SE: 0.089) at baseline and improved to 0.35 (SE: 0.10, p = 0.002), reaching a statistically significant difference at 3 months. A repeat implant led to VA improvement of 0.184 logMAR (SE: 0.171 logMAR) and CRT reduction of -291 um (SE: 74 um). There was no significant difference in effect between the first repeat implant and the initial implant. Kaplan-Meier estimates of treatment success were 72% between 3 and 6 months. CONCLUSIONS: The DEX implant is an effective adjunct treatment to systemic corticosteroid or immunomodulatory therapy. Additional research is required to determine the efficacy of DEX implant as monotherapy for controlling chronic uveitic macular edema. PMID- 27191688 TI - Efficacy of Human Fibrinogen-Thrombin Patch (TachoSil) Clinical Application in Upper Gastrointestinal Cancer Surgery. AB - BACKGROUND: Previous studies investigated the efficacy and applicability of tissue adhesives in gastrointestinal surgery while no evidence is available to date about a novel compound, TachoSil (Takeda, Zurich, Switzerland). The primary aim of this observational study was to assess the effect of new fibrin sealant on the incidence of postoperative complications in a homogeneous group of patients submitted to upper gastrointestinal surgery for cancer. METHODS: Two cohorts of 28 and 34 patients undergoing upper gastrointestinal for surgery were compared. In the first cohort, the anastomotic site was treated with TachoSil fibrinogen thrombin-collagen patches and in the second no collagen sponge or any other hemostatic sealant was used. Postoperative complications and outcomes as well as postoperative biochemical parameters were analyzed. RESULTS: Postoperative complications occurred in 12 patients (35.3%) and 2 patients (7.1%) in control and collagen sponge group respectively (chi2 = 3.539, p < 0.05), with no anastomotic leakage in the collagen sponge group. A binary logistic regression analysis showed that the nonuse of collagen sponge [odds ratio (OR) = 0.025, 95% confidence interval (CI) = 0.001-0.457, p = 0.01] was independently associated with postoperative complication occurrence. CONCLUSIONS: The addition of fibrinogen-thrombin-collagen sponge patch may reduce postoperative complication rate after upper gastrointestinal surgery for cancer. Further study to delineate the role of TachoSil in gastrointestinal surgery are also needed to demonstrate improved effectiveness and applicability. PMID- 27191687 TI - Nephroblastomatosis or Wilms tumor in a fourth patient with a somatic PIK3CA mutation. AB - Wilms tumor and nephroblastomatosis are associated with syndromic conditions including hemihyperplasia. Hemihyperplasia is genetically heterogeneous and may be the result of genomic abnormalities seen in Beckwith-Wiedemann syndrome, mosaic chromosome or genomic abnormalities, or somatic point mutations. Somatic missense mutations affecting the PI3K-AKT-MTOR pathway result in segmental overgrowth and are present in numerous benign and malignant tumors. Here, we report a fourth patient with asymmetric overgrowth due to a somatic PIK3CA mutation who had nephroblastomatosis or Wilms tumor. Similar to two of three reported patients with a somatic PIK3CA mutation and renal tumors, he shared a PIK3CA mutation affecting codon 1047, presented at birth with asymmetric overgrowth, and had fibroadipose overgrowth. Codon 1047 is most commonly affected by somatic mutations in PIK3CA-related overgrowth spectrum (PROS). While the fibroadipose overgrowth phenotype appears to be common in individuals with PIK3CA mutations at codon 1047, individuals with a clinical diagnosis of Klippel Trenaunay syndrome or isolated lymphatic malformation also had mutations affecting this amino acid. Screening for Wilms tumor in individuals with PROS related hemihyperplasia may be considered and, until the natural history is fully elucidated in larger cohort studies, may follow guidelines for Beckwith-Wiedemann syndrome, or isolated hemihyperplasia. It is not known if the specific PIK3CA mutation, the mosaic distribution, or the clinical presentation affect the Wilms tumor or nephroblastomatosis risk in individuals with PROS. (c) 2016 Wiley Periodicals, Inc. PMID- 27191690 TI - Adaptation of Perceptual Responses to Low-Load Blood Flow Restriction Training. AB - Martin-Hernandez, J, Ruiz-Aguado, J, Herrero, AJ, Loenneke, JP, Aagaard, P, Cristi-Montero, C, Menendez, H, and Marin, PJ. Adaptation of perceptual responses to low-load blood flow restriction training. J Strength Cond Res 31(3): 765-772, 2017-The purpose of this study was to determine the adaptive response of ratings of perceived exertion (RPE) and pain over 6 consecutive training sessions. Thirty subjects were assigned to either a blood flow restriction training (BFRT) group or a high-intensity resistance training (HIT) group. Blood flow-restricted training group performed 4 sets (30 + 15 + 15 + 15, respectively) of unilateral leg extension at an intensity of 20% one repetition maximum (1RM) while a restrictive cuff was applied to the most proximal part of the leg. The HIT group performed 3 sets of 8 repetitions with 85% 1RM. Ratings of perceived exertion and pain were assessed immediately after each exercise set along the 6 training sessions and were then averaged to obtain the overall RPE and pain per session. Statistical analyses showed significant main effects for group (p <= 0.05) and time (p < 0.001). Ratings of perceived exertion values dropped from session 1 to session 6 in both BFRT (8.12 +/- 1.3 to 5.7 +/- 1.1, p < 0.001) and HIT (8.5 +/- 1.2 to 6.40 +/- 1.2, p < 0.001). Similar results were observed regarding pain ratings (BFRT: 8.12 +/- 1.3 to 5.90 +/- 1.55, p < 0.001; HIT: 6.22 +/- 1.7 to 5.14 +/- 1.42, p < 0.01). Our results indicate that RPE was higher after HIT, whereas differences did not reach significance regarding pain. These perceptual responses were attenuated over time, and the time course of this adaptive response was similar between BFRT and HIT. In summary, BFRT induces a marked perceptual response to training, comparable with that observed with HIT. However, this response becomes attenuated with continuous practice, leading to moderate values of RPE and pain. Perceptual responses may not limit the application of BFRT to highly motivated individuals. PMID- 27191691 TI - Effect of Time-of-Day on Biochemical Markers in Response to Physical Exercise. AB - Ammar, A, Chtourou, H, and Souissi, N. Effect of time-of-day on biochemical markers in response to physical exercise. J Strength Cond Res 31(1): 272-282, 2017-It is well established that many physiological functions are time-of-day (TOD) dependent, and their circadian rhythms are well documented in healthy populations at resting state. In fact, greater rate of oxidative stress, white blood cell, homocysteine, and muscle damage markers were shown in the early evening (~18:00 hours), and more efficient antioxidant activity was observed in the early morning (~06:00 hours). During physical tasks, the majority of the above-mentioned physiological functions increase from pre to post physical exercise with different rates of increases from morning to evening. These different rates of increases are suggested to alter the physiological resting diurnal variation. In this context, given the possible significant interaction "TOD * physical exercise," circadian rhythms of the physiological responses during physical activity are still not well established in trained subjects. Otherwise, it was suggested that the diurnal variation of these biochemical parameters could, in part, explain the typical diurnal fluctuation of physical performance. Therefore, the aim of this review was to summarize the currently available studies investigating the circadian rhythms of physiological functions at rest and after physical exercise and to establish their possible effect on the diurnal variation of sport performance. Although studies in this field are limited, the available information shows that compared with sedentary subjects, trained population maintained similar diurnal variations of hematological parameters, homocysteine, and some biochemical markers at rest and even after physical exercise. However, after strength exercises, the circadian rhythms for the majority of oxidative stress and muscle damage markers were altered because of the higher rate of increased pre-post exercises registered in the morning compared with the afternoon and evening. The available studies reveal that the significant circadian variation observed for sport performances could be more likely explained by the alteration of ionic movement and the diurnal fluctuation of homocysteine, lactate, muscle damage, and antioxidant markers. PMID- 27191689 TI - Final overall survival results of a randomized trial comparing bortezomib plus pegylated liposomal doxorubicin with bortezomib alone in patients with relapsed or refractory multiple myeloma. AB - BACKGROUND: Previous results from an interim analysis of an open-label, randomized, phase 3 study demonstrated that bortezomib combined with pegylated liposomal doxorubicin (PLD) was superior to bortezomib monotherapy in patients with relapsed/refractory multiple myeloma who had previously received one or more lines of therapy. Protocol-defined final survival data from that study are provided here. METHODS: Patients were randomized (1:1) to receive either bortezomib alone (1.3 mg/m(2) intravenously on days 1, 4, 8, and 11 of every 21 day cycle) or bortezomib-PLD (bortezomib plus PLD 30 mg/m(2) intravenously on day 4). The primary endpoint was the time to progression. Secondary efficacy endpoints included overall survival (OS), progression-free survival, and the overall response rate. RESULTS: In total, 646 patients (bortezomib-PLD, n = 324; bortezomib alone, n = 322) were randomized between December, 2004, and March, 2006. On the clinical cutoff date (May 16, 2014) for the final survival analysis, at a median follow-up of 103 months, 79% of patients had died (bortezomib-PLD group: 253 of 324 patients; 78%; bortezomib alone group: 257 of 322 patients; 80%). The median OS in the bortezomib-PLD group was 33 months (95% confidence interval [CI], 28.9-37.1) versus 30.8 months (95% CI, 25.2-36.5) in the bortezomib alone group (hazard ratio, 1.047; 95% CI, 0.879-1.246; P = .6068). Salvage therapies included conventional and novel drugs, which were well balanced between the two treatment groups. CONCLUSIONS: Despite inducing a superior time to progression, long-term follow-up revealed that PLD-bortezomib did not improve OS compared with bortezomib alone in patients with relapsed/refractory multiple myeloma. The inability to sustain the early observed survival advantage may have been caused by the effects of subsequent lines of therapy, and underscores the need for long-term follow-up of phase 3 trials while recognizing the challenge of having adequate power to detect long-term differences in OS. Cancer 2016;122:2050 6. (c) 2016 American Cancer Society. PMID- 27191692 TI - Electromyographical Comparison of Pike Variations Performed With and Without Instability Devices. AB - Snarr, RL, Hallmark, AV, Nickerson, BS, and Esco, MR. Electromyographical comparison of pike variations performed with and without instability devices. J Strength Cond Res 30(12): 3436-3442, 2016-Instability devices are primarily used with the intent of increasing the intensity of traditional exercises by providing further muscular demands of the abdominal wall by decreasing stability. Although there are multiple studies examining these devices, most often they only compare one such device to a stable movement and overlook the comparison among multiple devices. The purpose of this investigation was to compare the electromyographical differences of the rectus abdominis (RA), external oblique (EO), erector spinae (LSES), and rectus femoris (RF) during pike variations performed on various surfaces. Twenty men and women volunteered for this study. All subjects performed 5 variations of a pike on varying surfaces (i.e., stable ground [PK], Swiss ball [SB], suspension training device [ST], BOSU ball [BOSU], and Core Coaster [CC]). Normalized (%MVC) values were recorded for each muscle during 5 repetitions of each pike variations. For the RA, EO, LSES, and RF, the PK elicited significantly lower values compared with the instability devices. In terms of the EO, the ST was significantly higher than the BOSU, SB, and CC. Results of this investigation demonstrated significant differences between the instability devices and the stable pike. These results indicate that with more freely moving instability devices (e.g., suspension device, Swiss ball, etc.), core musculature may require greater muscular demands. Practitioners should take note that traditional stable pikes may not offer a core musculature challenge to resistance-trained individuals. PMID- 27191693 TI - Effects of 16 Weeks of Concurrent Training on Resting Heart Rate Variability and Cardiorespiratory Fitness in People Living With HIV/AIDS Using Antiretroviral Therapy: A Randomized Clinical Trial. AB - Pedro, RE, Guariglia, DA, Okuno, NM, Deminice, R, Peres, SB, and Moraes, SMF. Effects of 16 weeks of concurrent training on resting heart rate variability and cardiorespiratory fitness in people living with HIV/AIDS using antiretroviral therapy: a randomized clinical trial. J Strength Cond Res 30(12): 3494-3502, 2016 The study evaluated the effects of concurrent training on resting heart rate variability (HRVrest) and cardiorespiratory fitness in people living with HIV/AIDS undergoing antiretroviral therapy (ART). Fifty-eight participants were randomized into 2 groups (control and training group); however, only 33 were analyzed. The variables studied were HRVrest indices, submaximal values of oxygen uptake (V[Combining Dot Above]O2sub) and heart rate (HR5min), peak speed (Vpeak), and peak oxygen uptake (V[Combining Dot Above]O2peak). The training group performed concurrent training (15-20 minutes of aerobic exercise plus 40 minutes of resistance exercise), 3 times per week, for 16 weeks. Posttraining V[Combining Dot Above]O2peak and Vpeak increased, and HR5min decreased. Resting heart rate variability indices did not present statistical differences posttraining; however, the magnitude-based inferences demonstrated a "possibly positive effect" for high frequency (HF) and low frequency (LF) plus high frequency (LF + HF) and a "likely positive effect" for R-Rmean posttraining. In conclusion, concurrent training was effective at improving cardiorespiratory fitness and endurance performance. Moreover, it led to probably a positive effect on HF and a likely positive effect on R-Rmean in people living with HIV/AIDS undergoing ART. PMID- 27191694 TI - The Running Performance Profile of Elite Gaelic Football Match-Play. AB - : Malone, S, Solan, B, and Collins, K. TITLE: The running performance profile of elite Gaelic football match-play. J Strength Cond Res 31(1): 30-36, 2017-The current study examined (a) the match running performance of Gaelic football and (b) the decrement in match running performance with respect to position. Global positioning satellite system technologies (4-Hz; VX Sport) were used with 3 elite intercounty teams across 3 full seasons with 250 full game data sets collected. Game movements were classified according to game actions and distance covered across speed zone thresholds (total distance [TD], high-speed running distance [HSRD; >=17 km.h], sprint distance [SD; >=22 km.h]; accelerations [n]; peak speed [km.h]). The influence of running performance in each quarter on the subsequent quarter was analyzed across all positional roles. The mean (+/-SD) TD and HSRD covered during the game were 8,889 +/- 1,448 m and 1,596 +/- 594 m, respectively. Results show a temporal profile for TD with reductions in the second (-4.1%), third (-5.9%) and fourth (-3.8%) quarters, respectively. There was a significant reduction in HSRD in the second (-8.8%), third (-15.9%), and fourth (-19.8%) quarters when compared to the first quarter (p < 0.001). Positional differences were observed for distance-based measures with the middle 3 positions (half-back, midfield, and half-forward) completing the highest running performances. These positions also showed increased decrements in TD and HSRD and SD across quarters. The current data indicate a reduction in exercise intensity over the duration of elite Gaelic football match-play. It is unclear if this reduction is because of fatigue, pacing, contextual factors, or nutritional strategies employed by players. PMID- 27191695 TI - Warm-up Practices in Elite Boxing Athletes: Impact on Power Output. AB - Cunniffe, B, Ellison, M, Loosemore, M, and Cardinale, M. Warm-up practices in elite boxing athletes: Iimpact on power output. J Strength Cond Res 31(1): 95 105, 2017-This study evaluated the performance impact of routine warm-up strategies in elite Olympic amateur boxing athletes and physiological implications of the time gap (GAP) between warm-up and boxing activity. Six male boxers were assessed while performing standardized prefight warm-up routines. Core and skin temperature measurements (Tcore and Tskin), heart rate, and upper- and lower-body power output (PO) were assessed before and after warm-up, during a 25-minutes GAP and after 3 * 2 minutes rounds of sparring. Reflected temperature (Tc) was also determined using high-resolution thermal images at fixed time points to explore avenues for heat loss. Despite individual differences in warm up duration (range 7.4-18.5 minutes), increases in Tcore and Tskin occurred (p <= 0.05). Corresponding increases (4.8%; p <= 0.05) in countermovement jump (CMJ) height and upward-rightward shifts in upper-body force-velocity and power velocity curves were observed. Athletes remained inactive during the 25-minutes GAP with a gradual and significant increase in Tc occurring by the end of GAP suggesting the likelihood of heat loss. Decreases in CMJ height and upper-body PO were observed after 15 minutes and 25 minutes GAP (p <= 0.05). By the end of GAP period, all performance variables had returned to pre-warm-up values. Results suggest routine warm-ups undertaken by elite boxers have acute effects on power generating capacity. Gradual decreases in performance variables are evident with inactivity and seem related to alterations in body temperature. Considering the constraints of major competitions and time spent in air conditioned holding areas before fights, practitioners should be aware of the potential of nullifying the warm-up effects. PMID- 27191696 TI - Maximal Aerobic Frequency of Ball Hitting: A New Training Load Parameter in Tennis. AB - Baiget, E, Iglesias, X, and Rodriguez, FA. Maximal aerobic frequency of ball hitting: a new training load parameter in tennis. J Strength Cond Res 31(1): 106 114, 2017-This study aimed (a) to evaluate a new training load parameter in tennis based on the ball-hitting frequency (Ballf) at V[Combining Dot Above]O2max occurs (maximal aerobic frequency of ball hitting, MAF) and (b) to assess the accuracy of a specific endurance tennis test (SET-Test) for predicting MAF. Thirty-five male competitive tennis players performed the SET-Test and selected physiological and performance parameters at maximal workload (MAX), and last completed stage (LS) and MAF were compared. Performance parameters (Ballf, time, stage, and hits per test) at LS were higher than at MAF (20.2 +/- 1.7 vs. 18.1 +/ 1.5 shots.min, 6.6 +/- 0.8 vs. 5.6 +/- 0.8 stages, and 189 +/- 33 vs. 147 +/- 27 hits; p < 0.001), and highly correlated (r = 0.72-0.77; p < 0.001). The mean difference between Ballf and stage at MAF and LS were 2.1 +/- 1.1 shots.min and 1.1 +/- 0.6 stages, respectively. The main physiological parameters (heart rate, V[Combining Dot Above]O2, and V[Combining Dot Above]CO2 at LS) were higher than at MAF (191 +/- 9 vs. 186 +/- 8 beats.min, 55.5 +/- 5.9 vs. 55.0 +/- 6.0 ml.kg.min and 4,724 +/- 880 vs. 4,253 +/- 739 ml.min; p < 0.005), and were very strongly correlated (r = 0.93-0.99; p < 0.001). We conclude that MAF can be used as a practical performance parameter to prescribe tennis-specific training, and that the SET-Test is a valid method for assessing MAF. Gas exchange measurements not being available, as a rule of thumb, most players reach their MAF at ~1 stage (95% confidence interval: 0.9-1.2) and ~2 shots.min (95% confidence interval: 1.7 2.5) less than their completed LS. A model for specific on-court training protocols for optimizing aerobic fitness in competitive tennis player is proposed. PMID- 27191697 TI - Effects of Short or Long Warm-up on Intermediate Running Performance. AB - van den Tillaar, R, Vatten, T, and von Heimburg, E. Effects of short or long warm up on intermediate running performance. J Strength Cond Res 31(1): 37-44, 2017 The aim of the study was to compare the effects of a long warm-up (general + specific) and a short warm-up (specific) on intermediate running performance (3 minute run). Thirteen experienced endurance-trained athletes (age 23.2 +/- 2.3 years, body mass 79.8 +/- 8.2 kg, body height 1.82 +/- 0.05 m) conducted 2 types of warm-ups in a crossover design with 1 week in between: a long warm-up (10 minutes, 80% maximal heart rate, and 8 * 60 m sprint with increasing intensity and 1 minute rest in between) and a short warm-up (8 * 60 m sprint with increasing intensity and 1 minute rest in between). Each warm-up was followed by a 3-minute running test on a nonmotorized treadmill. Total running distance, running velocity at each 30 seconds, heart rate, blood lactate concentration, oxygen uptake, and rate of perceived exertion were measured. No significant differences in running performance variables and physiological parameters were found between the 2 warm-up protocols, except for the rate of perceived exertion and heart rate, which were higher after the long warm-up and after the 3-minute running test compared with the short warm-up. It was concluded that a short warm up is as effective as a long warm-up for intermediate performance. Therefore, athletes can choose for themselves if they want to include a general part in their warm-up routines, even though it would not enhance their running performance more compared with only using a short, specific warm-up. However, to increase efficiency of time for training or competition, these short, specific warm-ups should be performed instead of long warm-ups. PMID- 27191698 TI - Comparison of Olympic and Hexagonal Barbells With Midthigh Pull, Deadlift, and Countermovement Jump. AB - Malyszek, KK, Harmon, RA, Dunnick, DD, Costa, PB, Coburn, JW, and Brown, LE. Comparison of olympic and hexagonal barbells with midthigh pull, deadlift, and countermovement jump. J Strength Cond Res 31(1): 140-145, 2017-Those training for strength and power commonly use different bars and different lifts. The hexagonal barbell (HBar) and Olympic barbell (OBar) are frequently used training implements, and the midthigh pull (MTP) and deadlift (DL) are 2 popular exercises. Therefore, the purpose of this study was to compare force between an HBar and OBar for a MTP, DL, and countermovement jump (CMJ). Twenty resistance trained men (age = 24.05 +/- 2.09 years, ht = 178.07 +/- 7.05 cm, mass = 91.42 +/ 14.44 kg) volunteered to participate and performed MTP and DL using both bars and a CMJ. Joint angles were recorded for all pulls and the bottom position of the CMJ. Peak ground reaction force (PGRF) was greater in the MTP (3,186.88 +/- 543.53 N) than DL (2,501.15 +/- 404.04 N) but not different between bars. Midthigh pull joint angles were more extended than DL, and the strongest correlations between isometric and dynamic performance were seen between DL PGRF and CMJ impulse (OBar r = 0.85; HBar r = 0.84). These findings are likely because of the different anatomical characteristics between the MTP and DL and the similarity in joint angles between the DL and CMJ. Therefore, the DL may be an optimal choice for athletes in jump-dependent sports, regardless of bar. PMID- 27191699 TI - Neisseria gonorrhoeae Resistant to Ceftriaxone and Cefixime, Argentina. PMID- 27191700 TI - Stealth Research and Theranos: Reflections and Update 1 Year Later. PMID- 27191702 TI - Errors in Identification of 17 of 527 Brain Images in Genetic Study of Phenotypes Associated With Bipolar Disorder. PMID- 27191701 TI - Long and short (timeframe) of endoplasmic reticulum stress-induced cell death. AB - A number of age-dependent degenerative diseases are caused by chronic endoplasmic reticulum (ER) stress in vital cells. In many cases, the afflicted cells suffer from ER stress since birth, but the death of irreplaceable cells occurs only late in life. Although our understanding of ER stress-induced cell death has advanced significantly, most of the known mechanisms involve pathways that signal within hours, and it remains unclear how these pathways regulate cell death that occurs only decades later. Here, I highlight the conceptual issues and suggest ways to make sense of the age-related effect of ER stress-induced cell death in degenerative diseases. PMID- 27191703 TI - Transcription Factor Drug Targets. AB - Transcription factors represent the point of convergence of multiple signaling pathways within eukaryotic cells. Deregulated transcription factors contribute to the pathogenesis of a plethora of human diseases, ranging from diabetes, inflammatory disorders and cardiovascular disease to many cancers, and thus these proteins hold great therapeutic potential. Direct modulation of transcription factor function by small molecules is no longer regarded a Sisyphean task, as recent work in drug discovery has revealed that transcription factors are amenable to drug inhibition. Here in we summarize, recent advances regarding the significance of transcription factors in human diseases and we discuss emerging pharmacological strategies to modulate transcription factor function. J. Cell. Biochem. 117: 2693-2696, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27191704 TI - Does trust of patients in their physician predict loyalty to the health care insurer? The Israeli case study. AB - This pioneer study tests the relationship between patients' trust in their physicians and patients' loyalty to their health care insurers. This is a cross sectional study using a representative sample of patients from all health care insurers with identical health care plans. Regression analyses and Baron and Kenny's model were used to test the study model. Patient trust in the physician did not predict loyalty to the insurer. Loyalty to the physician did not mediate the relationship between trust in the physician and loyalty to the insurer. Satisfaction with the physician was the only predictor of loyalty to the insurer. PMID- 27191705 TI - Modern Radiological Imaging of Osteoarthritis of The Hip Joint With Consideration of Predisposing Conditions. AB - Osteoarthritis is the most common disease of the hip joint in adults and has a high socioeconomic impact. This review article discusses the value of three imaging modalities in the diagnosis of osteoarthritis of the hip joint: projection radiography, computed tomography, and magnetic resonance imaging (MRI). Besides established imaging diagnostics of osteoarthritis, this review also outlines new MRI techniques that enable the biochemical analysis of hip joint cartilage and discusses predisposing deformities of the hip joint including femoroacetabular impingement (FAI) with labral pathologies, hip joint dysplasia, malrotation, and, finally, femoral head necrosis, for which early detection and an exact description of the extent and localization of the necrotic area are extremely important. Conventional X-rays remain indispensable for the diagnosis of osteoarthritis, while MRI is able to depict additional early symptoms and signs of activity of the disease. With the increasing number of joint-preserving interventions such as surgical hip luxation and hip joint arthroscopy for treating FAI, high-resolution imaging is gaining further importance for both pre- and postoperative diagnostics because it can accurately recognize early stages of joint damage. With high-resolution MR sequences and MR arthrography, the detailed depiction of the thin cartilaginous coating of the hip joint has become quite possible. KEY POINTS: * Projection radiography is the method of choice for the diagnostic work-up of osteoarthritis of the hip joint.* Using computed tomography, the amount of acetabular bone stock prior to total hip arthroplasty is assessed in selected patients.* Magnetic resonance imaging can substantiate the indication of surgery in case of discrepancy between clinical symptoms and radiological findings of the hip joint.* If distinct and left untreated, predisposing conditions (such as femoroacetabular impingement) may lead to early development of osteoarthritis of the hip joint.* Functional cartilage imaging can verify changes in the biochemical composition of the cartilage before they become morphologically evident. Citation Format: * Weber MA, Merle C, Rehnitz C et al. Modern Radiological Imaging of Osteoarthritis of The Hip Joint With Consideration of Predisposing Conditions. Fortschr Rontgenstr 2016; 188: 635 - 651. PMID- 27191706 TI - Heterogenized Bimetallic Pd-Pt-Fe3O4 Nanoflakes as Extremely Robust, Magnetically Recyclable Catalysts for Chemoselective Nitroarene Reduction. AB - A very simple synthesis of bimetallic Pd-Pt-Fe3O4 nanoflake-shaped alloy nanoparticles (NPs) for cascade catalytic reactions such as dehydrogenation of ammonia-borane (AB) followed by the reduction of nitro compounds (R-NO2) to anilines or alkylamines (R-NH2) in methanol at ambient temperature is described. The Pd-Pt-Fe3O4 NPs were easily prepared via a solution phase hydrothermal method involving the simple one-pot coreduction of potassium tetrachloroplatinate (II) and palladium chloride (II) in polyvinylpyrrolidone with subsequent deposition on commercially available Fe3O4 NPs. The bimetallic Pd-Pt alloy NPs decorated on Fe3O4 NPs provide a unique synergistic effect for the catalysis of cascade dehydrogenation/reduction. Various nitroarene derivatives were reduced to anilines with very specific chemoselectivity in the presence of other reducible functional groups. The bimetallic Pd-Pt-Fe3O4 NPs provide a unique synergistic effect for the catalysis of cascade dehydrogenation/reduction. The nitro reduction proceeded in 5 min with nearly quantitative conversions and yields. Furthermore, the magnetically recyclable nanocatalysts were readily separated using an external magnet and reused up to 250 times without any loss of catalytic activity. A larger scale (10 mmol) reaction was also successfully performed with >99% yield. This efficient, recyclable Pd-Pt-Fe3O4 NPs system can therefore be repetitively utilized for the reduction of various nitro-containing compounds. PMID- 27191708 TI - Trait and State Levels of Loneliness in Early and Late Adolescents: Examining the Differential Reactivity Hypothesis. AB - According to the differential reactivity hypothesis, lonely individuals respond differently to their environment compared to nonlonely individuals, which may sustain their loneliness levels. However, this interesting hypothesis has not yet been explored in daily life: Do lonely individuals feel lonely all the time, or do they feel more or less lonely in specific social contexts? The main aim of the present study was to test the differential reactivity hypothesis in daily life by examining in three samples whether trait levels of loneliness affected the levels of state loneliness in different social contexts. We used baseline questionnaires to measure trait loneliness and the Experience Sampling Method to collect data on state loneliness, in early adolescents (N = 269, Mage = 14.49, 59% female) and late adolescents (N = 223, Mage = 19.60, 91% female) from the Netherlands and late adolescents from the United States (N = 126, Mage = 19.20, 51% female). Results provided evidence for the differential reactivity hypothesis in the total sample, as high lonely adolescents experienced higher levels of state loneliness in situations in which they were alone than low lonely adolescents, but also benefited more from being with intimate company than low lonely adolescents. In sum, the present study provided evidence for the differential reactivity hypothesis and showed that the experience of loneliness in daily life was remarkably similar across age and culture. Our findings provide important insights into the daily experiences of trait lonely people, which may provide starting points for interventions. PMID- 27191707 TI - Exploiting mitochondria as targets for the development of new antifungals. AB - Mitochondria are essential for cell growth and survival of most fungal pathogens. Energy (ATP) produced during oxidation/reduction reactions of the electron transport chain (ETC) Complexes I, III and IV (CI, CIII, CIV) fuel cell synthesis. The mitochondria of fungal pathogens are understudied even though more recent published data suggest critical functional assignments to fungal-specific proteins. Proteins of mammalian mitochondria are grouped into 16 functional categories. In this review, we focus upon 11 proteins from 5 of these categories in fungal pathogens, OXPHOS, protein import, stress response, carbon source metabolism, and fission/fusion morphology. As these proteins also are fungal specific, we hypothesize that they may be exploited as targets in antifungal drug discovery. We also discuss published transcriptional profiling data of mitochondrial CI subunit protein mutants, in which we advance a novel concept those CI subunit proteins have both shared as well as specific responsibilities for providing ATP to cell processes. PMID- 27191710 TI - Handbook on Medical Student Evaluation and Assessment. PMID- 27191709 TI - A combination of soy isoflavones and cello-oligosaccharides changes equol/O desmethylangolensin production ratio and attenuates bone fragility in ovariectomized mice. AB - We examined the cooperative effects of isoflavones and cello-oligosaccharides on daidzein metabolism and bone fragility in ovariectomized mice. Cello oligosaccharides increased urinary equol and decreased O-desmethylangolensin. A combination of isoflavones and cello-oligosaccharides attenuated decreases in bone breaking force and stiffness caused by ovariectomy. Combination treatment with isofalvones and cello-oligosaccharides increases urinary equol/O desmethylangolensin production ratio and prevents ovariectomy-induced abnormalities in bone strength. PMID- 27191711 TI - Discriminatory usefulness of pulsed-field gel electrophoresis and sequence-based typing in Legionella outbreaks. AB - AIM: To compare the discriminatory power of pulsed-field gel electrophoresis (PFGE) and sequence-based typing (SBT) in Legionella outbreaks for determining the infection source. MATERIALS & METHODS: Twenty-five investigations of Legionnaires' disease were analyzed by PFGE, SBT and Dresden monoclonal antibody. RESULTS: The results suggested that monoclonal antibody could reduce the number of Legionella isolates to be characterized by molecular methods. The epidemiological concordance PFGE-SBT was 100%, while the molecular concordance was 64%. Adjusted Wallace index (AW) showed that PFGE has better discriminatory power than SBT (AWSBT->PFGE = 0.767; AWPFGE->SBT = 1). The discrepancies appeared mostly in sequence type (ST) 1, a worldwide distributed ST for which PFGE discriminated different profiles. CONCLUSION: SBT discriminatory power was not sufficient verifying the infection source, especially in worldwide distributed STs, which were classified into different PFGE patterns. PMID- 27191712 TI - Rapid Detection of Polymyxin Resistance in Enterobacteriaceae. AB - For identification of polymyxin resistance in Enterobacteriaceae, we developed a rapid test that detects glucose metabolization associated with bacterial growth in the presence of a defined concentration of colistin or polymyxin B. Formation of acid metabolites is evidenced by a color change (orange to yellow) of a pH indicator (red phenol). To evaluate the test, we used bacterial colonies of 135 isolates expressing various mechanisms of colistin resistance (intrinsic, chromosomally encoded, and plasmid-mediated MCR-1) and 65 colistin-susceptible isolates. Sensitivity and specificity were 99.3% and 95.4%, respectively, compared with the standard broth microdilution method. This new test is inexpensive, easy to perform, sensitive, specific, and can be completed in <2 hours. It could be useful in countries facing endemic spread of carbapenemase producers and for which polymyxins are last-resort drugs. PMID- 27191713 TI - Copper-Catalyzed Three-Component Reaction for Regioselective Aryl- and Heteroarylselenation of Indoles using Selenium Powder. AB - A new and efficient copper-catalyzed C3 aryl- and heteroarylselenation of indoles employing selenium powder has been developed. The advantages of this chemistry involve the use of cheap selenating reagents, tolerance of a variety of functional groups, and practicality. In addition, this protocol has been further elaborated in an intramolecular phenylselenation of a (hetero) aryl C-H bond to construct an important motif of benzoselenopheno[3,2-b]indole. A preliminary mechanism study suggests that the reaction starts with a Ullman-type selenation between aryl iodides and selenium, followed by an oxidative cross-coupling with indole. The utility of this method has been demonstrated in an efficient gram scale synthesis and an application to the synthesis of tubulin polymerization inhibitor. PMID- 27191714 TI - Antipsychotic-Induced Neuroleptic Malignant Syndrome After Cardiac Surgery. AB - We report a case of neuroleptic malignant syndrome (NMS) in a postoperative cardiac surgery patient after the administration of typical and atypical antipsychotics for the treatment of delirium. On postoperative day 8, the patient's temperature peaked at 40.6 degrees C. Agitation, rigidity, elevation in creatine kinase, and leukocytosis were associated findings. NMS was suspected on postoperative day 10. All antipsychotics were discontinued; dantrolene infusions and fluid therapy were initiated. After 2 days of NMS treatment, the patient's symptoms resolved. The temporal relationship between discontinuation of all antipsychotics, initiation of dantrolene, and clinical improvement supports the diagnosis of antipsychotic-induced NMS. PMID- 27191717 TI - The Effects of Run-of-River Hydroelectric Power Schemes on Fish Community Composition in Temperate Streams and Rivers. AB - The potential environmental impacts of large-scale storage hydroelectric power (HEP) schemes have been well-documented in the literature. In Europe, awareness of these potential impacts and limited opportunities for politically-acceptable medium- to large-scale schemes, have caused attention to focus on smaller-scale HEP schemes, particularly run-of-river (ROR) schemes, to contribute to meeting renewable energy targets. Run-of-river HEP schemes are often presumed to be less environmentally damaging than large-scale storage HEP schemes. However, there is currently a lack of peer-reviewed studies on their physical and ecological impact. The aim of this article was to investigate the effects of ROR HEP schemes on communities of fish in temperate streams and rivers, using a Before-After, Control-Impact (BACI) study design. The study makes use of routine environmental surveillance data collected as part of long-term national and international monitoring programmes at 23 systematically-selected ROR HEP schemes and 23 systematically-selected paired control sites. Six area-normalised metrics of fish community composition were analysed using a linear mixed effects model (number of species, number of fish, number of Atlantic salmon-Salmo salar, number of >1 year old Atlantic salmon, number of brown trout-Salmo trutta, and number of >1 year old brown trout). The analyses showed that there was a statistically significant effect (p<0.05) of ROR HEP construction and operation on the number of species. However, no statistically significant effects were detected on the other five metrics of community composition. The implications of these findings are discussed in this article and recommendations are made for best-practice study design for future fish community impact studies. PMID- 27191716 TI - Chimeric Mice with Competent Hematopoietic Immunity Reproduce Key Features of Severe Lassa Fever. AB - Lassa fever (LASF) is a highly severe viral syndrome endemic to West African countries. Despite the annual high morbidity and mortality caused by LASF, very little is known about the pathophysiology of the disease. Basic research on LASF has been precluded due to the lack of relevant small animal models that reproduce the human disease. Immunocompetent laboratory mice are resistant to infection with Lassa virus (LASV) and, to date, only immunodeficient mice, or mice expressing human HLA, have shown some degree of susceptibility to experimental infection. Here, transplantation of wild-type bone marrow cells into irradiated type I interferon receptor knockout mice (IFNAR-/-) was used to generate chimeric mice that reproduced important features of severe LASF in humans. This included high lethality, liver damage, vascular leakage and systemic virus dissemination. In addition, this model indicated that T cell-mediated immunopathology was an important component of LASF pathogenesis that was directly correlated with vascular leakage. Our strategy allows easy generation of a suitable small animal model to test new vaccines and antivirals and to dissect the basic components of LASF pathophysiology. PMID- 27191715 TI - Maintenance of Stem Cell Niche Integrity by a Novel Activator of Integrin Signaling. AB - Stem cells depend critically on the surrounding microenvironment, or niche, for their maintenance and self-renewal. While much is known about how the niche regulates stem cell self-renewal and differentiation, mechanisms for how the niche is maintained over time are not well understood. At the apical tip of the Drosophila testes, germline stem cells (GSCs) and somatic stem cells share a common niche formed by hub cells. Here we demonstrate that a novel protein named Shriveled (Shv) is necessary for the maintenance of hub/niche integrity. Depletion of Shv protein results in age-dependent deterioration of the hub structure and loss of GSCs, whereas upregulation of Shv preserves the niche during aging. We find Shv is a secreted protein that modulates DE-cadherin levels through extracellular activation of integrin signaling. Our work identifies Shv as a novel activator of integrin signaling and suggests a new integration model in which crosstalk between integrin and DE-cadherin in niche cells promote their own preservation by maintaining the niche architecture. PMID- 27191719 TI - Mass Extinction and the Disappearance of Unknown Mammal Species: Scenario and Perspectives of a Biodiversity Hotspot's Hotspot. AB - We aimed to determine the conservation status of medium- and large-sized mammals and evaluate the impact of 500 years of forest fragmentation on this group of animals in the Pernambuco Endemism Center, in the biogeographical zone of the Atlantic forest north of the Sao Francisco River in northeastern Brazil. Line transect surveys were performed in 21 forest fragments, resulting in a checklist of the mammals of the entire Pernambuco Endemism Center area. We ran a generalized linear model (Factorial ANCOVA) to analyze to what extent the vegetation type, fragment area, isolation, sampling effort (as total kilometers walked), or higher-order interactions predicted (a) richness and (b) sighting rates. To determine if the distribution of the species within the forest fragments exhibited a nested pattern, we used the NODF metric. Subsequently, we performed a Binomial Logistic Regression to predict the probability of encountering each species according to fragment size. Out of 38 medium- and large sized mammal species formerly occurring in the study area, only 53.8% (n = 21) were sighted. No fragment hosted the entire remaining mammal community, and only four species (19%) occurred in very small fragments (73.3% of the remaining forest fragments, with a mean size of 2.8 ha). The mammalian community was highly simplified, with all large mammals being regionally extinct. Neither the species richness nor sighting rate was controlled by the vegetation type, the area of the forest fragments, isolation or any higher-order interaction. Although a highly significant nested subset pattern was detected, it was not related to the ranking of the area of forest fragments or isolation. The probability of the occurrence of a mammal species in a given forest patch varied unpredictably, and the probability of detecting larger species was even observed to decrease with increasing patch size. In an ongoing process of mass extinction, half of the studied mammals have gone extinct. The remaining medium-sized mammal community is highly simplified and homogenized. The persistence of these species in a forest patch is determined by their ability to adapt to a novel simplified diet, the efficient use of the surrounding matrix without being engulfed by the sink effect, and escaping hunting. Our results suggest that the 21st century medium sized mammalian fauna of this region will comprise only four species unless strict conservation measures are implemented immediately and every forest fragment is effectively protected. PMID- 27191718 TI - The Lake Chad Basin, an Isolated and Persistent Reservoir of Vibrio cholerae O1: A Genomic Insight into the Outbreak in Cameroon, 2010. AB - The prevalence of reported cholera was relatively low around the Lake Chad basin until 1991. Since then, cholera outbreaks have been reported every couple of years. The objective of this study was to investigate the 2010/2011 Vibrio cholerae outbreak in Cameroon to gain insight into the genomic make-up of the V. cholerae strains responsible for the outbreak. Twenty-four strains were isolated and whole genome sequenced. Known virulence genes, resistance genes and integrating conjugative element (ICE) elements were identified and annotated. A global phylogeny (378 genomes) was inferred using a single nucleotide polymorphism (SNP) analysis. The Cameroon outbreak was found to be clonal and clustered distant from the other African strains. In addition, a subset of the strains contained a deletion that was found in the ICE element causing less resistance. These results suggest that V. cholerae is endemic in the Lake Chad basin and different from other African strains. PMID- 27191721 TI - Limited Capacity for Faster Digestion in Larval Coral Reef Fish at an Elevated Temperature. AB - The prevalence of extreme, short-term temperature spikes in coastal regions during summer months is predicted to increase with ongoing climate change. In tropical systems, these changes are predicted to increase the metabolic demand of coral reef fish larvae while also altering the plankton communities upon which the larvae feed during their pelagic phase. The consequences of these predictions remain speculative in the absence of empirical data on the interactive effects of warm temperatures on the metabolism, postprandial processes and growth responses of coral reef fish larvae. Here, we tested the effect of increased temperature on the metabolism, postprandial performance and fine-scale growth patterns of a coral reef fish (Amphiprion percula) in the latter half of its ~11-d larval phase. First, we measured the length and weight of fed versus fasted larvae (N = 340; mean body mass 4.1+/-0.05 mg) across fine temporal scales at a typical current summer temperature (28.5 degrees C) and a temperature that is likely be encountered during warm summer periods later this century (31.5 degrees C). Second, we measured routine metabolic rate (Mo2 routine) and the energetics of the postprandial processes (i.e., digestion, absorption and assimilation of a meal; termed specific dynamic action (SDA)) at both temperatures. Larvae fed voraciously when provided with food for a 12-hour period and displayed a temperature-independent increase in mass of 40.1% (28.5 degrees C) and 42.6% (31.5 degrees C), which was largely associated with the mass of prey in the gut. A subsequent 12-h fasting period revealed that the larvae had grown 21.2+/-4.8% (28.5 degrees C) and 22.8+/-8.8% (31.5 degrees C) in mass and 10.3+/-2.0% (28.5 degrees C) and 7.8+/-2.6% (31.5 degrees C) in length compared with pre-feeding values (no significant temperature effect). Mo2 routine was 55+/-16% higher at 31.5 degrees C and peak Mo2 during the postprandial period was 28+/-11% higher at 31.5 degrees C, yet elevated temperature had no significant effect on SDA (0.51+/ 0.06 J at 28.5 degrees C vs. 0.53+/-0.07 J at 31.5 degrees C), SDA duration (6.0+/-0.6 h vs. 6.5+/-0.5 h), or the percent of total meal energy used for SDA (SDA coefficient: 10.1+/-1.3% vs. 13.0+/-1.7%). Our findings of higher Mo2 routine but similar SDA coefficient at high temperature provide the first empirical evidence that coral reef fish larvae may have to secure more food to attain similar growth rates during warm summer periods, and perhaps with chronically warmer conditions associated with climate change. PMID- 27191720 TI - Integrated and Functional Genomics Analysis Validates the Relevance of the Nuclear Variant ErbB380kDa in Prostate Cancer Progression. AB - The EGF-family of tyrosine-kinase receptors activates cytoplasmic pathways involved in cell proliferation, migration and differentiation in response to specific extracellular ligands. Beside these canonical pathways, the nuclear localization of the ErbB receptors in primary tumours and cancer cell lines led to investigate their role as transcriptional regulators of cancer genes. The nuclear localization of ErbB3 has been reported in various cancer tissues and cell lines but the nuclear functions and the putative correlation with tumour progression and resistance to therapy remain unclear. We first assessed ErbB3 expression in normal and tumour prostate tissues. The nuclear staining was mainly due to an isoform matching the C-terminus domain of the full length ErbB3185kDa receptor. Nuclear staining was also restricted to cancer cells and was increased in advanced castration-resistant prostate cancer when compared to localized tumours, suggesting it could be involved in the progression of prostate cancer up to the terminal castration-resistant stage. ChIP-on-chip experiments were performed on immortalized and tumour cell lines selected upon characterization of endogenous nuclear expression of an ErbB380kDa isoform. Among the 1840 target promoters identified, 26 were selected before ErbB380kDa-dependent gene expression was evaluated by real-time quantitative RT-PCR, providing evidence that ErbB380kDa exerted transcriptional control on those genes. Some targets are already known to be involved in prostate cancer progression even though no link was previously established with ErbB3 membrane and/or nuclear signalling. Many others, not yet associated with prostate cancer, could provide new therapeutic possibilities for patients expressing ErbB380kDa. Detecting ErbB380kDa could thus constitute a useful marker of prognosis and response to therapy. PMID- 27191722 TI - Species Identification in Malaise Trap Samples by DNA Barcoding Based on NGS Technologies and a Scoring Matrix. AB - The German Barcoding initiatives BFB and GBOL have generated a reference library of more than 16,000 metazoan species, which is now ready for applications concerning next generation molecular biodiversity assessments. To streamline the barcoding process, we have developed a meta-barcoding pipeline: We pre-sorted a single malaise trap sample (obtained during one week in August 2014, southern Germany) into 12 arthropod orders and extracted DNA from pooled individuals of each order separately, in order to facilitate DNA extraction and avoid time consuming single specimen selection. Aliquots of each ordinal-level DNA extract were combined to roughly simulate a DNA extract from a non-sorted malaise sample. Each DNA extract was amplified using four primer sets targeting the CO1-5' fragment. The resulting PCR products (150-400bp) were sequenced separately on an Illumina Mi-SEQ platform, resulting in 1.5 million sequences and 5,500 clusters (coverage >=10; CD-HIT-EST, 98%). Using a total of 120,000 DNA barcodes of identified, Central European Hymenoptera, Coleoptera, Diptera, and Lepidoptera downloaded from BOLD we established a reference sequence database for a local CUSTOM BLAST. This allowed us to identify 529 Barcode Index Numbers (BINs) from our sequence clusters derived from pooled Malaise trap samples. We introduce a scoring matrix based on the sequence match percentages of each amplicon in order to gain plausibility for each detected BIN, leading to 390 high score BINs in the sorted samples; whereas 268 of these high score BINs (69%) could be identified in the combined sample. The results indicate that a time consuming presorting process will yield approximately 30% more high score BINs compared to the non sorted sample in our case. These promising results indicate that a fast, efficient and reliable analysis of next generation data from malaise trap samples can be achieved using this pipeline. PMID- 27191723 TI - BMP4 Signaling Is Able to Induce an Epithelial-Mesenchymal Transition-Like Phenotype in Barrett's Esophagus and Esophageal Adenocarcinoma through Induction of SNAIL2. AB - BACKGROUND: Bone morphogenetic protein 4 (BMP4) signaling is involved in the development of Barrett's esophagus (BE), a precursor of esophageal adenocarcinoma (EAC). In various cancers, BMP4 has been found to induce epithelial-mesenchymal transition (EMT) but its function in the development of EAC is currently unclear. AIM: To investigate the expression of BMP4 and several members of the BMP4 pathway in EAC. Additionally, to determine the effect of BMP4 signaling in a human Barrett's esophagus (BAR-T) and adenocarcinoma (OE33) cell line. METHODS: Expression of BMP4, its downstream target ID2 and members of the BMP4 pathway were determined by Q-RT-PCR, immunohistochemistry and Western blot analysis using biopsy samples from EAC patients. BAR-T and OE33 cells were incubated with BMP4 or the BMP4 antagonist, Noggin, and cell viability and migration assays were performed. In addition, expression of factors associated with EMT (SNAIL2, CDH1, CDH2 and Vimentin) was evaluated by Q-RT-PCR and Western blot analysis. RESULTS: Compared to squamous epithelium (SQ), BMP4 expression was significantly upregulated in EAC and BE. In addition, the expression of ID2 was significantly upregulated in EAC and BE compared to SQ. Western blot analysis confirmed our results, showing an upregulated expression of BMP4 and ID2 in both BE and EAC. In addition, more phosphorylation of SMAD1/5/8 was observed. BMP4 incubation inhibited cell viability, but induced cell migration in both BAR-T and OE33 cells. Upon BMP4 incubation, SNAIL2 expression was significantly upregulated in BAR-T and OE33 cells while CDH1 expression was significantly downregulated. These results were confirmed by Western blot analysis. CONCLUSION: Our results indicate active BMP4 signaling in BE and EAC and suggest that this results in an invasive phenotype by inducing an EMT-like response through upregulation of SNAIL2 and subsequent downregulation of CDH1. PMID- 27191724 TI - Using Big Data to Assess Prescribing Patterns in Greece: The Case of Chronic Obstructive Pulmonary Disease. AB - INTRODUCTION: Chronic Obstructive Pulmonary Disease (COPD) is one of the top leading causes of death and disability, and its management is focused on reducing risk factors, relieving symptoms, and preventing exacerbations. The study aim was to describe COPD prescribing patterns in Greece by using existing health administrative data for outpatients. METHODS: This is a retrospective cross sectional study based on prescriptions collected by the largest social insurance fund, during the first and last trimester of 2012. Selection criteria were the prescription of specific active substances and a COPD diagnosis. Extracted information included active substance, strength, pharmaceutical form and number of packages prescribed, diagnosis, time of dispensing, as well as insurees' age, gender, percentage of co-payment and social security unique number. Statistical analysis included descriptive statistics and logistic regression. RESULTS: 174,357 patients received medicines for COPD during the study period. Patients were almost equally distributed between male and female, and age above 55 years was strongly correlated with COPD. Most patients received a long-acting beta agonist plus inhaled corticosteroid combination (LABA +ICS), followed by long acting muscarinic agonist (LAMA). 63% patients belonging in the 35-54 age received LABA+ICS. LAMA was prescribed more frequently among males and was strongly correlated with COPD. CONCLUSION: The study provides big data analysis of Greek COPD prescribing patterns. It highlights the need for appropriate COPD classification in primary care illustrating the role of electronic prescribing in ensuring appropriate prescribing. Moreover, it indicates possible gender differences in treatment response or disease severity, and the impact of statutory co-payments on prescribing. PMID- 27191726 TI - The mechanistic-holistic divide revisited: The case of the lac operon. AB - In this paper, I revisit the development of the repression model of genetic regulation in the lac operon to challenge a common application of a conceptual framework in the history of biology. I take Allen's (1978) account of the changes in the life sciences during the early and mid-twentieth century as an example of a common application of a framework based on the dichotomy between a mechanistic, or reductionist, approach to science and a holistic one. From this conceptual framework, Allen infers two general claims about the process of science and its goals: (1) that "mechanistic materialism" has often presented a more practical way to begin the study of complex phenomena in the life sciences, and (2) that the approach described as "holistic materialism" provides a more complete or accurate description of the natural world. The development of the lac operon model does not fit Allen's generalizations about scientific developments, and it can be used to cast some doubt on the scope of application of that conceptual framework. I argue that a better framework to interpret particular episodes in the history of molecular biology is to consider the ways in which biologists prioritize and track different aspects of the phenomena under study, rather than to focus on whether certain scientific practices are best described as developing from mechanistic to more holistic approaches. I end with some implications for the historiography of science by considering the appropriateness of different conceptual frameworks for different grains of resolution in the history of biology. PMID- 27191725 TI - Triclosan Exposure Is Associated with Rapid Restructuring of the Microbiome in Adult Zebrafish. AB - Growing evidence indicates that disrupting the microbial community that comprises the intestinal tract, known as the gut microbiome, can contribute to the development or severity of disease. As a result, it is important to discern the agents responsible for microbiome disruption. While animals are frequently exposed to a diverse array of environmental chemicals, little is known about their effects on gut microbiome stability and structure. Here, we demonstrate how zebrafish can be used to glean insight into the effects of environmental chemical exposure on the structure and ecological dynamics of the gut microbiome. Specifically, we exposed forty-five adult zebrafish to triclosan-laden food for four or seven days or a control diet, and analyzed their microbial communities using 16S rRNA amplicon sequencing. Triclosan exposure was associated with rapid shifts in microbiome structure and diversity. We find evidence that several operational taxonomic units (OTUs) associated with the family Enterobacteriaceae appear to be susceptible to triclosan exposure, while OTUs associated with the genus Pseudomonas appeared to be more resilient and resistant to exposure. We also found that triclosan exposure is associated with topological alterations to microbial interaction networks and results in an overall increase in the number of negative interactions per microbe in these networks. Together these data indicate that triclosan exposure results in altered composition and ecological dynamics of microbial communities in the gut. Our work demonstrates that because zebrafish afford rapid and inexpensive interrogation of a large number of individuals, it is a useful experimental system for the discovery of the gut microbiome's interaction with environmental chemicals. PMID- 27191728 TI - A Systematic Review of Social Media Use to Discuss and View Deliberate Self-Harm Acts. AB - OBJECTIVE: To conduct a systematic review of studies of social media platforms used by young people to discuss and view deliberate self-harm. STUDY DESIGN: 11 electronic databases were searched from January 2000 to January 2012 for primary research; in June 2014 an updated search of Medline was conducted. Grey literature sources were also searched. Search results were screened by two reviewers. Data were extracted by one reviewer and verified by another. Methodological quality was assessed using the Mixed Methods Appraisal Tool. RESULTS: Due to heterogeneity in study objectives and outcomes, results were not pooled; a narrative analysis is presented. 26 studies were included. Most were conducted in Canada or the UK (30.8% each), used qualitative designs (42.3%), and evaluated discussion forums (73.1%). Participants were most often aged 19-21 years (69.2%), female (mean 68.6%), and 19.2% had a documented history of depression. The social media platforms evaluated were commonly supportive and provided a sense of community among users. Support included suggestions for formal treatment, advice on stopping self-harming behavior, and encouragement. Harms included normalizing and accepting self-harming behavior; discussion of motivation or triggers, concealment, suicidal ideation or plans; and live depictions of self-harm acts. CONCLUSIONS: Although this evidence is limited by its descriptive nature, studies identify beneficial and detrimental effects for young people using social media to discuss and view deliberate self-harm. The connections users make online may be valuable to explore for therapeutic benefit. Prospective, longitudinal investigations are needed to identify short- and long term potential harms associated with use. PMID- 27191727 TI - Morning and Evening Blue-Enriched Light Exposure Alters Metabolic Function in Normal Weight Adults. AB - Increasing evidence points to associations between light-dark exposure patterns, feeding behavior, and metabolism. This study aimed to determine the acute effects of 3 hours of morning versus evening blue-enriched light exposure compared to dim light on hunger, metabolic function, and physiological arousal. Nineteen healthy adults completed this 4-day inpatient protocol under dim light conditions (<20lux). Participants were randomized to 3 hours of blue-enriched light exposure on Day 3 starting either 0.5 hours after wake (n = 9; morning group) or 10.5 hours after wake (n = 10; evening group). All participants remained in dim light on Day 2 to serve as their baseline. Subjective hunger and sleepiness scales were collected hourly. Blood was sampled at 30-minute intervals for 4 hours in association with the light exposure period for glucose, insulin, cortisol, leptin, and ghrelin. Homeostatic model assessment of insulin resistance (HOMA-IR) and area under the curve (AUC) for insulin, glucose, HOMA-IR and cortisol were calculated. Comparisons relative to baseline were done using t-tests and repeated measures ANOVAs. In both the morning and evening groups, insulin total area, HOMA IR, and HOMA-IR AUC were increased and subjective sleepiness was reduced with blue-enriched light compared to dim light. The evening group, but not the morning group, had significantly higher glucose peak value during blue-enriched light exposure compared to dim light. There were no other significant differences between the morning or the evening groups in response to blue-enriched light exposure. Blue-enriched light exposure acutely alters glucose metabolism and sleepiness, however the mechanisms behind this relationship and its impacts on hunger and appetite regulation remain unclear. These results provide further support for a role of environmental light exposure in the regulation of metabolism. PMID- 27191730 TI - Total Synthesis of Teixobactin. AB - The first total synthesis of the cyclic depsipeptide natural product teixobactin is described. Synthesis was achieved by solid-phase peptide synthesis, incorporating the unusual l-allo-enduracididine as a suitably protected synthetic cassette and employing a key on-resin esterification and solution-phase macrolactamization. The synthetic natural product was shown to possess potent antibacterial activity against a range of Gram-positive pathogenic bacteria, including a virulent strain of Mycobacterium tuberculosis and methicillin resistant Staphylococcus aureus (MRSA). PMID- 27191731 TI - Patterns of Uveitis and Scleritis in Nepal: A Tertiary Referral Center Study. AB - PURPOSE: To analyze the patterns of uveitis and scleritis at the tertiary referral center in Nepal. METHODS: A retrospective review of uveitis and scleritis cases at Tilganga Institute of Ophthalmology in 2014. RESULTS: A total of 1113 uveitis, 73 scleritis, 35 sclerouveitis cases were reviewed. Anterior uveitis (590, 53%) was most common, followed by panuveitis (20%), intermediate uveitis (14%), then posterior uvietis (12.9%). The most common causes of anterior, pan, and posterior uveitis were herpetic disease (15.1%), SHAPU (15.2%) and toxoplamosis (27.1%) respectively. The most common cause of scleritis & sclerouveitis was Tuberculosis (15.1%, 31.4% respectively). CONCLUSION: Herpetic disease, toxoplasmosis, tuberculosis and SHAPU were common infections. PMID- 27191733 TI - Mind MELD or Ignore It at Your Peril. PMID- 27191729 TI - Lumbar Myeloid Cell Trafficking into Locomotor Networks after Thoracic Spinal Cord Injury. AB - Spinal cord injury (SCI) promotes inflammation along the neuroaxis that jeopardizes plasticity, intrinsic repair and recovery. While inflammation at the injury site is well-established, less is known within remote spinal networks. The presence of bone marrow-derived immune (myeloid) cells in these areas may further impede functional recovery. Previously, high levels of the gelatinase, matrix metalloproteinase-9 (MMP-9) occurred within the lumbar enlargement after thoracic SCI and impeded activity-dependent recovery. Since SCI-induced MMP-9 potentially increases vascular permeability, myeloid cell infiltration may drive inflammatory toxicity in locomotor networks. Therefore, we examined neurovascular reactivity and myeloid cell infiltration in the lumbar cord after thoracic SCI. We show evidence of region-specific recruitment of myeloid cells into the lumbar but not cervical region. Myeloid infiltration occurred with concomitant increases in chemoattractants (CCL2) and cell adhesion molecules (ICAM-1) around lumbar vasculature 24h and 7days post injury. Bone marrow GFP chimeric mice established robust infiltration of bone marrow-derived myeloid cells into the lumbar gray matter 24h after SCI. This cell infiltration occurred when the blood-spinal cord barrier was intact, suggesting active recruitment across the endothelium. Myeloid cells persisted as ramified macrophages at 7days post injury in parallel with increased inhibitory GAD67 labeling. Importantly, macrophage infiltration required MMP-9. PMID- 27191734 TI - Fixation Characteristics of Severe Amblyopia Subtypes: Which One is Worse? AB - PURPOSE: To determine differences in macular sensitivity and fixation patterns in different subtypes of severe amblyopia. METHODS: This case-control study enrolled a total of 73 male adults, including 18 with pure strabismic severe amblyopia, 19 with pure anisometropic severe amblyopia, 18 with mixed (strabismic plus anizometropic) severe amblyopia, and 18 healthy controls. MP-1 microperimetry was used to evaluate macular sensitivity, location of fixation, and stability of fixation. RESULTS: Mean macular sensitivity, stability of fixation, and location of fixation were significantly worse in all amblyopia subtypes when compared with healthy controls. Intergroup comparisons between amblyopia subtypes revealed that mean macular sensitivity, stability of fixation, and location of fixation were significantly worse in pure strabismic and mixed amblyopic eyes when compared with pure anisometropic amblyopic eyes. CONCLUSIONS: Strabismus seems to be a worse prognostic factor in severe amblyopia than anisometropia in terms of fixation characteristics and retinal sensitivity. PMID- 27191732 TI - Substance Use Profiles of Urban American Indian Adolescents: A Latent Class Analysis. AB - A growing majority of American Indian adolescents now live in cities and are at high risk of early and problematic substance use and its negative health effects. OBJECTIVE: This study used latent class analysis to empirically derive heterogeneous patterns of substance use among urban American Indian adolescents, examined demographic correlates of the resulting latent classes, and tested for differences among the latent classes in other risk behavior and prosocial outcomes. METHOD: The study employed a representative sample of 8th, 10th, and 12th grade American Indian adolescents (n = 2,407) in public or charter schools in metropolitan areas of Arizona in 2012. Latent class analysis examined eight types of last 30 day substance use. RESULTS: Four latent classes emerged: a large group of "nonusers" (69%); a substantial minority using alcohol, tobacco, and/or marijuana [ATM] (17%); a smaller group of polysubstance users consuming, alcohol, tobacco, marijuana, other illicit drugs, and prescription or OTC drugs in combination (6%); and a "not alcohol" group reporting combinations of tobacco, marijuana, and prescription drug use, but rarely alcohol use (4%). The latent classes varied by age and grade level, but not by other demographic characteristics, and aligned in highly consistent patterns on other non-substance use outcomes. Polysubstance users reported the most problematic and nonusers the least problematic outcomes, with ATM and "not alcohol" users in the middle. CONCLUSIONS: Urban AI adolescent substance use occurs in three somewhat distinctive patterns of combinations of recent alcohol and drug consumption, covarying in systematic ways with other problematic risk behaviors and attitudes. PMID- 27191735 TI - Epidemiology of Pulmonary Nontuberculous Mycobacterial Disease, Japan(1). PMID- 27191736 TI - One carbon metabolism, a complex metabolic network involved in pathomechanisms of inherited disorders, birth defects and age-related pathologies. PMID- 27191737 TI - Quantitative transportation assessment in curved canals prepared with an off centered rectangular design system. AB - The purpose of this study was to assess the ability of an off-centered rectangular design system [ProTaper Next (PTN)] to maintain the original profile of the root canal anatomy. To this end, ProTaper Universal (PTU), Reciproc (R) and WaveOne (WO) systems were used as reference techniques for comparison. Forty clear resin blocks with simulated curved root canals were randomly assigned to 4 groups (n = 10) according to the instrumentation system used: PTN, PTU, R and WO. Color stereomicroscopic images of each block were taken before and after instrumentation. All image processing and data analysis were performed with an open source program (Fiji v.1.47n). Evaluation of canal transportation was obtained for two independent regions: straight and curved portions. Univariate analysis of variance and Tukey's Honestly Significant Difference test were performed, and a cut-off for significance was set at alpha = 5%. Instrumentation systems significantly influenced canal transportation (p = 0.000). Overall, R induced significantly lower canal transportation compared with WO, PTN and PTU (p = 0.000). The curved portion displayed superior canal transportation compared to the straight one (p = 0.000). The significance of the difference among instrumentation systems varied according to the canal level evaluated (p = 0.000). In its straight portion, R and WO exhibited significantly lower transportation than PTN; whereas in the curved portion, R produced the lowest deviation. PTU exhibited the highest canal transportation at both levels. It can be concluded that PTN produced less canal transportation than PTU and WO; however, R exhibited better centering ability than PTN. PMID- 27191738 TI - Histomorphometric evaluation of strontium-containing nanostructured hydroxyapatite as bone substitute in sheep. AB - The aim of this study is to evaluate the biocompatibility and osteoconductivity in surgical defects of sheep tibias filled with 1% strontium-containing nanostructured hydroxyapatite microspheres (SrHA), stoichiometric hydroxyapatite without strontium microspheres (HA), or blood clots. Santa Ines sheep were subjected to three perforations on the medial side of the left tibia. The biomaterials were characterized by X-ray Diffraction (XRD) and Fourier Transform Infrared (FTIR) before implantation and by X-Ray Microfluorescence (uFRX) and Scanning Electron Microscopy (SEM) after sheep tibias implantation. Surgical defects were filled with blood clots (control), SrHA (Group 1) or HA (Group 2). After 30 days, 5-um bone blocks were obtained for histological evaluation, and the blocks obtained from 1 animal were embedded in methylmethacrylate for undecalcified sections. Mononuclear inflammatory infiltrate remained mild in all experimental groups. Giant cells were observed surrounding biomaterials particles of both groups and areas of bone formation were detected in close contact with biomaterials. All groups showed newly formed bone from the periphery to the center of the defects, which the control, HA and SrHA presented 36.4% (+/- 21.8), 31.2% (+/- 14.7) and 26.2% (+/- 12.9) of newly formed bone density, respectively, not presenting statistical differences. In addition, the connective tissue density did not show any significant between groups. The SrHA showing a higher volume density of biomaterial (51.2 +/- 14.1) present in the defect compared to HA (32.6 +/- 8.5) after 30 days (p = 0.03). Microspheres containing 1% SrHA or HA can be considered biocompatible, have osteoconductive properties and may be useful biomaterials for clinical applications. PMID- 27191739 TI - Effect of irrigation technique for removal of triple antibiotic paste on bond strength of MTA to root dentin. AB - This study evaluated the bond strength of mineral trioxide aggregate (MTA) to root canal dentin after the performance of various irrigation procedures to remove triple antibiotic paste (TAP). A total of 56 single-rooted human mandibular premolars were instrumented using a rotary system to size 40 and divided randomly into a control group (no intracanal dressing) and three experimental groups (TAP application for 28 days). TAP was then removed by rinsing with 10 mL 2.5% NaOCl using three irrigation systems (Vibringe sonic irrigation, CanalBrush, and syringe irrigation). The coronal and middle parts of root canals were then obturated with MTA. After storage for 1 week, each specimen was embedded in an acrylic block and sectioned horizontally (2-mm-thick slices) at two levels (coronal and middle). Bond strength of MTA to root canal dentin was assessed in 28 samples per group via push-out test using a universal testing machine. Data from the four groups were compared using one-way analysis of variance. Tukey's test was used for multiple comparisons. Push-out bond strength values were significantly higher in the control and Vibringe groups than in the CanalBrush and syringe irrigation groups (p < 0.001). TAP removal from root canals with the Vibringe irrigation system may increase the push-out bond strength of MTA compared with the use of the CanalBrush or syringe irrigation. PMID- 27191740 TI - Radiological characterization of clay mixed red mud in particular as regards its leaching features. AB - The reuse of industrial by-products such as red mud is of great importance. In the case of the building material industry the reuse of red mud requires a cautious attitude, since the enhanced radionuclide content of red mud can have an effect on human health. The natural radionuclide content of red mud from the Ajka red mud reservoir and the clay sample from a Hungarian brick factory were determined by gamma spectrometry. It was found that maximum 27.8% red mud content can be added to fulfil the conditions of the EU-BSS. The effect of heat treatment was investigated on a red mud-clay mixture and it was found that in the case of radon and thoron exhalation the applied heat reduced remarkably the exhalation capacities. The leaching features of red mud and different mixtures were studied according to the MSZ-21470-50 Hungarian standard, the British CEN/TS 14429 standard and the Tessier sequential extraction method. The Tessier method and the MSZ-21470-50 standard are suitable for the characterization of materials; however, they do not provide enough information for waste deposition purposes. To this end, we propose using the CEN/TS 14429 method, because it is easy to use, and gives detailed information about the material's behaviour under different pH conditions, however, further measurements are necessary. PMID- 27191741 TI - Estimation of sedimentation rates based on the excess of radium 228 in granitic reservoir sediments. AB - Knowledge of sedimentation rates in lakes is required to understand and quantify the geochemical processes involved in scavenging and remobilization of contaminants at the Sediment-Water Interface (SWI). The well-known 210Pb excess (210Pbex) method cannot be used for quantifying sedimentation rates in uranium enriched catchments, as large amounts of 210Pb produced by weathering and human activities may dilute the atmospheric 210Pb. As an alternative dating method in these cases, we propose an original method based on 232Th decay series nuclides. This study focuses on an artificial lake located in a granitic catchment downstream from a former uranium mine site. The exponential decay of 228Ra excess (228Raex) with depth in two long cores yields sedimentation rates of 2.4 and 5.2 cm yr-1 respectively. These sedimentation rates lead to the attribution of the 137Cs activity peak observed at depth to the Chernobyl fallout event of 1986. The 228Raex method was also applied to two short cores which did not display the 137Cs peak, and mean sedimentation rates of 2.1 and 4.0 cm y-1 were deduced. The proposed method may replace the classical radiochronological methods (210Pbex, 137Cs) to determine sedimentation rates in granitic catchments. PMID- 27191742 TI - GFOD1 and peejar are promising markers for clear-cell renal cell carcinoma disease progression. AB - Clear cell renal cell carcinoma (ccRCC) is a common genitourinary malignancy. The molecular pathogenesis of ccRCC remains unclear and biomarkers for daily practice were still limited. We performed an integrative analysis of two public ccRCC microarray datasets, E-GEOD-22541 and E-MTAB-1050, The candidate differential expression genes (DEG) were then confirmed in the E-GEOD-53757 dataset. In addition, an independent cohort of 50 ccRCC and 36 non-tumor kidney tissues were analyzed to examine the selected DGEs by qRT-PCR. We identified and validated two DEGs, namely GFOD1 and peejar, which were significantly up-regulated in ccRCC compared with normal renal tissues (p < 0.001). Moreover, the expression of these two genes are related to histological grade and stage and decrease of their expression correlated with disease progression (p < 0.05). Furthermore, we found the expression of peejar was positively correlated with the expression of GFOD1 in ccRCC tissue, with Pearson correlation coefficiency reaching 0.939 (p < 0.001). GFOD1 and peejar were novel genes correlated with ccRCC disease progression and patients' poor prognosis. PMID- 27191743 TI - CAPE suppresses migration and invasion of prostate cancer cells via activation of non-canonical Wnt signaling. AB - Prostate cancer (PCa) was the fifth most common cancer overall in the world. More than 80% of patients died from PCa developed bone metastases. Caffeic acid phenethyl ester (CAPE) is a main bioactive component of honeybee hive propolis. Transwell and wound healing assays demonstrated that CAPE treatment suppressed the migration and invasion of PC-3 and DU-145 PCa cells. Gelatin zymography and Western blotting indicated that CAPE treatment reduced the abundance and activity of MMP-9 and MMP-2. Analysis using Micro-Western Array (MWA), a high-throughput antibody-based proteomics platform with 264 antibodies detecting signaling proteins involved in important pathways indicated that CAPE treatment induced receptor tyrosine kinase-like orphan receptor 2 (ROR2) in non-canonical Wnt signaling pathway but suppressed abundance of beta-catenin, NF-kappaB activity, PI3K-Akt signaling, and epithelial-mesenchymal transition (EMT). Overexpression or knockdown of ROR2 suppressed or enhanced cell migration of PC-3 cells, respectively. TCF-LEF promoter binding assay revealed that CAPE treatment reduced canonical Wnt signaling. Intraperitoneal injection of CAPE reduced the metastasis of PC-3 xenografts in tail vein injection nude mice model. Immunohistochemical staining demonstrated that CAPE treatment increased abundance of ROR2 and Wnt5a but decreased protein expression of Ki67, Frizzle 4, NF-kappaB p65, MMP-9, Snail, beta-catenin, and phosphorylation of IkappaBalpha. Clinical evidences suggested that genes affected by CAPE treatment (CTNNB1, RELA, FZD5, DVL3, MAPK9, SNAl1, ROR2, SMAD4, NFKBIA, DUSP6, and PLCB3) correlate with the aggressiveness of PCa. Our study suggested that CAPE may be a potential therapeutic agent for patients with advanced PCa. PMID- 27191746 TI - The role of CEUS in characterization of superficial lymph nodes: a single center prospective study. AB - Accurate lymph node characterization is important in a large number of clinical settings. We evaluated the usefulness of Contrast Enhanced Ultrasound (CEUS) in distinguishing between benign and malignant lymph nodes compared with conventional ultrasonography in the differential diagnosis of superficial lymphadenopathy.We present our experience for 111 patients enrolled in a single center.111 superficial lymph nodes were selected and only 1 lymph node per patient underwent CEUS. A definitive diagnosis for all lymph nodes was obtained by ultrasonographically guided biopsy and/or excision biopsy.The size of the lymph nodes, the site (neck, axilla, inguinal region) being easily accessible for biopsy, and the US and color Doppler US characteristics guided us in selecting the nodes to be evaluated by CEUS.In our study we identified different enhancement patterns in benign and malignant lymph nodes, with a high degree of diagnostic accuracy for superficial lymphadenopathy in comparison with conventional US. PMID- 27191744 TI - Targeting tumor-associated macrophages to combat pancreatic cancer. AB - The tumor microenvironment is replete with cells that evolve with and provide support to tumor cells during the transition to malignancy. The hijacking of the immune system in the pancreatic tumor microenvironment is suggested to contribute to the failure to date to produce significant improvements in pancreatic cancer survival by various chemotherapeutics. Regulatory T cells, myeloid derived suppressor cells, and fibroblasts, all of which constitute a complex ecology microenvironment, can suppress CD8+ T cells and NK cells, thus inhibiting effector immune responses. Tumor-associated macrophages (TAM) are versatile immune cells that can express different functional programs in response to stimuli in tumor microenvironment at different stages of pancreatic cancer development. TAM have been implicated in suppression of anti-tumorigenic immune responses, promotion of cancer cell proliferation, stimulation of tumor angiogenesis and extracellular matrix breakdown, and subsequent enhancement of tumor invasion and metastasis. Many emerging agents that have demonstrated efficacy in combating other types of tumors via modulation of macrophages in tumor microenvironments are, however, only marginally studied for pancreatic cancer prevention and treatment. A better understanding of the paradoxical roles of TAM in pancreatic cancer may pave the way to novel preventive and therapeutic approaches. Here we give an overview of the recruitment and differentiation of macrophages, TAM and pancreatic cancer progression and prognosis, as well as the potential preventive and therapeutic targets that interact with TAM for pancreatic cancer prevention and treatment. PMID- 27191745 TI - Aldehyde dehydrogenase 2 inhibits inflammatory response and regulates atherosclerotic plaque. AB - Previous studies demonstrated that aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism, which eliminates ALDH2 activity down to 1%-6%, is a susceptibility gene for coronary disease. Here we investigated the underlying mechanisms based on our prior clinical and experimental studies. Male apoE-/- mice were transfected with GFP, ALDH2-overexpression and ALDH2-RNAi lentivirus respectively (n=20 each) after constrictive collars were placed around the right common carotid arteries. Consequently, ALDH2 gene silencing led to an increased en face plaque area, more unstable plaque with heavier accumulation of lipids, more macrophages, less smooth muscle cells and collagen, which were associated with aggravated inflammation. However, ALDH2 overexpression displayed opposing effects. We also found that ALDH2 activity decreased in atherosclerotic plaques of human and aged apoE-/- mice. Moreover, in vitro experiments with human umbilical vein endothelial cells further illustrated that, inhibition of ALDH2 activity resulted in elevating inflammatory molecules, an increase of nuclear translocation of NF-kappaB, and enhanced phosphorylation of NF-kappaB p65, AP-1 c Jun, Jun-N terminal kinase and p38 MAPK, while ALDH2 activation could trigger contrary effects. These findings suggested that ALDH2 can influence plaque development and vulnerability, and inflammation via MAPK, NF-kappaB and AP-1 signaling pathways. PMID- 27191747 TI - CXCL16 regulates cisplatin-induced acute kidney injury. AB - The pathogenesis of cisplatin-induced acute kidney injury (AKI) is characterized by tubular cell apoptosis and inflammation. However, the molecular mechanisms are not fully understood. We found that CXCL16 was induced in renal tubular epithelial cells in response to cisplatin-induced AKI. Therefore, we investigated whether CXCL16 played a role in cisplatin-induced tubular cell apoptosis and inflammation. Wild-type and CXCL16 knockout mice were administrated with vehicle or cisplatin at 20 mg/kg by intraperitoneal injection. CXCL16 knockout mice had lower blood urea nitrogen and less tubular damage following cisplatin-induced AKI as compared with wild-type mice. Genetic disruption of CXCL16 reduced tubular epithelial cell apoptosis and decreased caspase-3 activation. Furthermore, CXCL16 deficiency inhibited infiltration of macrophages and T cells into the kidneys following cisplatin treatment, which was associated with reduced expression of the proinflammatory cytokines in the kidneys. Taken together, our results indicate that CXCL16 plays a crucial role in the pathogenesis of cisplatin induced AKI through regulation of apoptosis and inflammation and maybe a novel therapeutic target for cisplatin-induced AKI. PMID- 27191753 TI - Food (and Water) for Thought. PMID- 27191752 TI - Doctor to Doctor. PMID- 27191754 TI - Problems+Solutions. PMID- 27191749 TI - Comparison of the early period effects of bone marrow-derived mesenchymal stem cells and platelet-rich plasma on the Achilles tendon ruptures in rats. AB - INTRODUCTION: This study aims to histopathologically, biomechanically, and immunohistochemically compare the fourth-week efficiencies of local platelet-rich plasma (PRP) and bone marrow-derived mesenchymal stem cell (rBM-MSC) treatments of the Achilles tendon ruptures created surgically in rats. MATERIALS AND METHODS: The study included 35 12-month-old male Sprague Dawley rats, with an average weight of 400-500 g. Five rats were used as donors for MSC and PRP, and 30 rats were separated into MSC, PRP, and control groups (n = 10). The Achilles tendons of the rats were cut transversely, the MSC from bone marrow was administered to the MSC group, the PRP group received PRP, and the control group received physiological saline to create the same surgical effect. In previous studies, it was shown that this physiological saline does not have any effect on tendon recovery. Thirty days after the treatment, the rats were sacrificed and their Achilles tendons were examined histopathologically, immunohistochemically, and biomechanically. RESULTS: The use of rBM-MSC and PRP in the Achilles tendon ruptures when the tendon is in its weakest phase positively affected the recovery of the tendon in histopathologic, immunohistochemical, and biomechanical manners compared to the control group (p < 0.05). While the levels of pro-inflammatory cytokines TNF-alpha, IFNgamma, and IL 1beta were significantly low, the levels of anti-inflammatory cytokines and growth factors playing key roles in tendon recovery, such as IL2, VEGF, transforming growth factor-beta, and HGF, were significantly higher in the MSC group than those of the PRP and control groups (p < 0.05). In the MSC group, the [Formula: see text] (mm) value was significantly higher (p ? 0.05) than that in the PRP and control groups. CONCLUSION: rBM-MSC and PRP promote the recovery of the tendon and increase its structural strength. The use of PRP and MSC provides hope for the treatment of the Achilles tendon ruptures that limit human beings' functionalities and quality of life, particularly for athletes. It is thought that the use of MSC can be more effective for tendon healing; hence, more extensive and advanced studies are needed on this topic. PMID- 27191755 TI - Readers' Forum. PMID- 27191748 TI - Combined experience of six independent laboratories attempting to create an Ewing sarcoma mouse model. AB - Ewing sarcoma (ES) involves a tumor-specific chromosomal translocation that produces the EWS-FLI1 protein, which is required for the growth of ES cells both in vitro and in vivo. However, an EWS-FLI1-driven transgenic mouse model is not currently available. Here, we present data from six independent laboratories seeking an alternative approach to express EWS-FLI1 in different murine tissues. We used the Runx2, Col1a2.3, Col1a3.6, Prx1, CAG, Nse, NEFL, Dermo1, P0, Sox9 and Osterix promoters to target EWS-FLI1 or Cre expression. Additional approaches included the induction of an endogenous chromosomal translocation, in utero knock in, and the injection of Cre-expressing adenovirus to induce EWS-FLI1 expression locally in multiple lineages. Most models resulted in embryonic lethality or developmental defects. EWS-FLI1-induced apoptosis, promoter leakiness, the lack of potential cofactors, and the difficulty of expressing EWS-FLI1 in specific sites were considered the primary reasons for the failed attempts to create a transgenic mouse model of ES. PMID- 27191756 TI - The Medical Bookshelf. PMID- 27191758 TI - Treatment of warts. PMID- 27191757 TI - Everyday minor surgery. PMID- 27191759 TI - Where does heroism really begin? PMID- 27191762 TI - Primary Care Digest. PMID- 27191760 TI - The 'retired MD syndrome'. PMID- 27191764 TI - Warts. PMID- 27191765 TI - Dose regimens for Chinese adult liver transplant recipients according to the genetic polymorphisms of CYP2C9, CYP2C19, and CYP3A5 in recipients and donors. AB - OBJECTIVE: Genetic polymorphisms of the P450 2C9 enzyme (CYP2C9), CYP2C19 and CYP3A5 gene are known to affect the metabolism of many drugs applied in liver transplant recipients, such as warfarin, voriconazole, and tacrolimus. The aim of this study was to recommend dose regimens for the liver recipients based on CYP2C9, CYP2C19, and CYP3A5 genotypic combinations of liver transplant recipients and their donors. METHODS: 91 adult Han Chinese liver transplant recipients who underwent orthotopic liver transplantation at Tianjin First Central Hospital, China, between 2013 and 2014 were included in this study. CYP2C9*2, CYP2C9*3, CYP2C19* 2, CYP2C19*3 and CYP3A5*3, in both liver recipients and their grafted liver were tested by polymerase chain reaction-restriction fragment length polymorphism. The dose regimens for the liver recipients were recommended based on CYP genotypic combinations of the recipients and their donors. RESULTS: In the liver transplant recipients, the frequencies of CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*3, and CYP3A5*3 were found to be 2.75%, 4.40%, 0%, 24.18%, and 75.27%, respectively. Allele frequencies were significantly different for CYP2C9*2, CYP2C19*2, and CYP2C19* 3 (p < 0.001) when comparing the recipients with Chinese, Eastern Asians and Caucasians populations. Most dose regimens of drugs, especially of immunosuppressive drugs, should be adjusted according to the variant metabolism activity affected by the genetic polymorphisms in both recipients and their grafted liver. CONCLUSION: The dose regimens would present considerable intraand inter-patient variability in liver transplant recipients since the genetic polymorphisms of P450 enzyme in their grafted liver might complicate the metabolism of drugs in liver transplant recipients. Giving careful consideration to the CYP genotypic combinations of transplant recipients and donors in clinical dose regimens could optimize outcomes. PMID- 27191766 TI - Population pharmacokinetics of ticagrelor in patients with acute coronary syndromes. AB - OBJECTIVE: Ticagrelor is an orally administered antiplatelet agent used to reduce thrombotic events in patients with acute coronary syndromes. Data from two studies in patients with acute coronary syndromes with large amounts of pharmacokinetic (PK) data (phase IIb DISPERSE-2 study (n = 609)); phase III PLATO PK substudy (n = 6,381)), along with non-linear mixed effects modeling software, were used to develop population PK models for ticagrelor and its metabolite, AR C124910XX, and to evaluate the impact of demographic and clinical factors on the PK of ticagrelor and AR-C124910XX. METHODS: 32 covariates relating to disease history, biomarkers, clinical chemistry, and concomitant medications were assessed. RESULTS: A one-compartment model with population mean PK parameters of firstorder absorption rate constant (0.67/h), apparent systemic clearance (14 L/h), and apparent volume of distribution (221 L) was shown to best describe the PK profile of ticagrelor. Patients co-administered moderate CYP3A inducers or inhibitors increased (by 110%, 95% confidence interval (CI), 52 - 192%) or decreased (by 64%, 95% CI, 39 - 73%) apparent ticagrelor clearance, respectively, while habitual smoking decreased apparent ticagrelor clearance by 22% (95% CI, 19 - 25%). Ticagrelor bioavailability was 21% (95% CI, 19 - 22%) lower at treatment initiation (visit 1) versus subsequent visits. Compared with Caucasian patients, ticagrelor bioavailability was 39% (95% CI, 33 - 46%) higher in Asian patients and 18% (95% CI, 6 - 28%) lower in Black patients. CONCLUSIONS: In the current analyses, the population PK models developed for ticagrelor and AR-C124910XX described the data obtained in the DISPERSE-2 and PLATO studies well, and were consistent with previous phase I PK studies. PMID- 27191767 TI - Pharmacokinetics of a nanocrystal-containing megestrol acetate formulation: a single-dose, randomized, open-label, 2-part, 2-period crossover study in healthy Korean subjects. AB - OBJECTIVE: The conventional suspension of megestrol acetate contains micronized megestrol acetate, which was recently discovered to have a disadvantage of decreasing bioavailability when taken in a fasting state. Since megestrol acetate is taken to increase appetite, this property becomes a discouraging factor. To improve upon this, an advanced formulation was developed using a nanocrystal drug-delivery system. This study was conducted to compare the safety and pharmacokinetic characteristics between the conventional formulation of megestrol acetate and a generic version of the advanced formulation containing nanocrystals. METHODS: This was a randomized, open-label, 2-period, 2 treatment, crossover, single-dose, 2-part study (part 1 fasting and part 2 fed), conducted in healthy males aged between 20 and 50 years with weight within +/- 20% of ideal body weight having no congenital abnormalities or chronic diseases. Different subjects were used in part 1 and part 2, but subjects received a single dose of the reference and test drugs separated by a 14-day washout period. Blood sampling was performed up to 120 hours after dosing using a pre-specified sampling time scheme. Primary pharmacokinetic parameters were Cmax and AUClast of the test and reference formulations of megestrol acetate. Bioequivalence evaluation was based on the standard criterion of 80 - 125% for the 90% confidence interval of geometric mean ratios of test to reference drugs calculated for the pharmacokinetic parameters. To monitor adverse events, both subject interviews and physical examinations were done on a regular time basis. RESULTS: 80 subjects (n = 40 each part) were enrolled, and 79 completed the study. The 90% CIs of the geometric mean ratios of Cmax and AUClast were 4.4625 - 5.6018 and 1.3602 - 1.6418, respectively, for part 1, and 0.9793 - 1.1327 and 0.7721 - 0.8431, respectively, for part 2. No significant difference was discovered in the incidence of adverse events (AEs) when test and reference treated groups were compared. CONCLUSIONS: Our findings suggest that the test formulation of megestrol-acetate-containing nanocrystals is better absorbed and has higher bioavailability compared to the reference formulation in a fasting state. This should allow for a lower dose and better patient compliance.

ClinicalTrials.gov identifier: NCT02446353. PMID- 27191768 TI - Effects of cardiovascular drugs on TSH serum levels in patients on replacement therapy after thyroidectomy. AB - OBJECTIVE: Hypothyroidism is one of most common endocrine disorders resulting from deficiency of thyroid hormones. The aim of our study was to investigate whether cardiovascular drugs as well as gender, age, body-mass index, and habits, like smoking or drinking coffee affect thyroid-stimulating hormone (TSH) level in hypothyroid patients with thyroxine replacement therapy who suffer from cardiovascular disease. MATERIALS: The study was conducted on 150 hypothyroid patients who underwent total thyroidectomy for benign reasons; they were divided into five treatment groups: levothyroxine only group and, according to the drugs they had in therapy alongside levothyroxine, the angiotensinconverting enzyme inhibitors group, the selective beta-blockers group, the calcium antagonists group, as well as the nitrates group. A retrospective cohort study was conducted in the Clinical Center Kragujevac, Serbia, during the period of January 2012 to October 2014. All patients' data were collected both from participants' health records and questionnaires that patients completed, including data about habits, like smoking or drinking coffee. RESULTS: TSH values were significantly higher in the group of patients with selective beta-blockers in therapy alongside levothyroxine, compared to all the other study groups. The values of TSH level did not significantly differ among the other therapy groups. On the other hand, cigarette smoking was a risk factor that decreased TSH levels in patients on thyroid replacement therapy. CONCLUSIONS: Our study shows that selective beta-1 blockers can increase, while cigarette smoking can decrease TSH serum levels in hypothyroid patients on thyroid-replacement therapy. PMID- 27191769 TI - Killian's photographs: "Facies dolorosa", the countenance of pain. AB - The book "Facies dolorosa" by Hans Killian, first published in 1934 and later in 1956 and 1967 as extended and annotated versions, comprises ~ 70 photographs depicting facial expressions of patients suffering from various diseases. The photographs in black and white are analyzed and annotated by the author with the purpose of providing clinicians, and especially young doctors, with an insight into the medical and scientific value of facial expression of pain in the diagnosis, staging, and prognosis of severe disease. This historical review of a book no longer in print is part of a 2016 commemorative publication marking the 60th anniversary of the publication of the "Facies dolorosa" by Dustri Medical and Scientific Publications, Munich, Germany and Rockledge, USA. PMID- 27191770 TI - Induced next-day somnolence in an elderly patient taking suvorexant concomitantly with diltiazem. AB - OBJECTIVE: To present the first case of induced next-day somnolence in a patient taking suvorexant concomitantly with diltiazem. CASE SUMMARY: The patient was an 88-year-old female who had suffered from insomnia and anorexia, for which a psychiatric clinic had prescribed 1.5 mg/day aripiprazole and 15 mg/day suvorexant (both once daily at bedtime), which cured her insomnia. Subsequently, a different hospital prescribed diltiazem hydrochloride (100 mg, sustained release, daily after breakfast) for treatment of hypertension. After starting diltiazem, the patient was unable to wake up in the morning and overslept by ~ 3 hours. On the third day of taking diltiazem, the patient, on the basis of her own judgment, took only half a tablet of suvorexant, and found that she was able to sleep, and there was no somnolence the following morning. As halving suvorexant tablets is an off-label usage, and lower-dose tablets are not available, her prescription was switched to 1-mg rilmazafone hydrochloride. Since then, her sleep disorder has not recurred. DISCUSSION: Because suvorexant is metabolized by CYP3A4, next-day somnolence could have occurred as a result of increased plasma suvorexant concentration due to CYP3A4 inhibition by diltiazem. CONCLUSION: Elderly patients may suffer next-day somnolence if they concomitantly take suvorexant and sustained-release diltiazem hydrochloride, even if the diltiazem dose is low and there is a significant interval between the administration times of the two drugs. In order to avoid drug interaction, it may be desirable to switch from suvorexant to a different soporific that is not metabolized by CYP3A4. PMID- 27191772 TI - Five-Year Secular Trends and Predictors of Nonconsent to Receive Donor Milk in the Neonatal Intensive Care Unit. AB - OBJECTIVE: To identify independent maternal and infant factors associated with donor milk nonconsent and to examine secular trends in nonconsent rates. MATERIALS AND METHODS: Mothers of infants eligible to receive donor milk (<=32 weeks of gestation or <=1,800 g) born between August 2010 and 2015 were included. Multivariable logistic regression modeled odds of nonconsent. RESULTS: Of the 486 mother/infant dyads from the first 5 years of the donor milk program, nonwhite race (adjusted odds ratio [aOR] 1.69; 95% confidence interval [CI] 1.04-2.76) and increasing gestational age (aOR 1.11; 95% CI 1.03-1.21) independently predicted nonconsent. Each year the program existed, there was a 48% reduction in odds of nonconsent (aOR 0.52; 95% CI 0.43-0.62). The most common reason given for nonconsent was "it's someone else's milk." CONCLUSION: Program duration was associated with reduced nonconsent rates and may reflect increased exposure to information and acceptance of donor milk use among neonatal intensive care unit staff and parents. Despite overall improvements in consent rates, race-specific disparities in rates of nonconsent for donor milk persisted after 5 years of this donor milk program. Further research is warranted to clarify the basis for race based disparities in donor milk nonconsent rates, with the goal of designing interventions to reduce donor milk refusal among minority mothers. PMID- 27191771 TI - FAAH inhibitors in the limelight, but regrettably. AB - This short review focuses on the recent drug development of FAAH inhibitors, as recent serious adverse events have been reported in a phase I study with a compound of this class. The authors overview the potential interest in targeting FAAH inhibition, the current programs, and the available information on the recent dramatic events. PMID- 27191773 TI - Synthesis, Radiolabeling, and Biological Evaluation of 5-Hydroxy-2 [(18)F]fluoroalkyl-tryptophan Analogues as Potential PET Radiotracers for Tumor Imaging. AB - Aiming at developing mechanism-based amino acid (18)F-PET tracers for tumor imaging, we synthesized two (18)F-labeled analogues of 5-hydroxy-l-[beta (11)C]tryptophan ([(11)C]5HTP) whose excellent in vivo performance in neuroendocrine tumors is mainly attributed to its decarboxylation by aromatic amino acid decarboxylase (AADC), an enzyme overexpressed in these malignancies. Reference compounds and precursors were synthesized following multistep synthetic approaches. Radiosynthesis of tracers was accomplished in good radiochemical yields (15-39%), high specific activities (45-95 GBq/MUmol), and excellent radiochemical purities. In vitro cell uptake was sodium-independent and was inhibited >=95% by 2-amino-2-norbornanecarboxylic acid (BCH) and ~30% by arginine. PET imaging in mice revealed distinctly high tumor/background ratios for both tracers, outperforming the well-established O-(2 [(18)F]fluoroethyl)tyrosine ([(18)F]FET) tracer in a head-to-head comparison. Biological evaluation revealed that the in vivo performance is most probably independent of any interaction with AADC. Nevertheless, the excellent tumor visualization qualifies the new tracers as interesting probes for tumor imaging worthy for further investigation. PMID- 27191774 TI - Reliability and validity of the Turkish translation of the beliefs about medicines questionnaire (BMQ-T) in patients with Behcet's disease. AB - OBJECTIVES: The aim of this study was to evaluate the reliability and validity of the Turkish translation of the Beliefs about Medicines Questionnaire (BMQ-T, (c)Prof. Rob Horne) for patients with Behcet's disease. METHODS: This methodological study enrolled a sample of 125 patients. The scale was adapted to Turkish through a process including translation, comparison with versions in other languages, back translation, and pretesting. Construct validity was evaluated by factor analysis. Medication adherence evaluated as poor, moderate and good according to the Morisky Medication Adherence Scale (MMAS). BMQ-T scores compared along medication adherence status groups. RESULTS: In our study, as in the original scale, the factor analysis confirmed that the BMQ-T had a four factor structure explaining 54.73% of the total variance. The BMQ-T had acceptable internal consistency (Cronbach's alpha coefficient: Specific Necessity=.812; Specific Concerns=.672; General Harm=.677; General Overuse=.656), adequate test-retest reliability (intraclass correlation coefficients: Specific Necessity=.715; Specific Concerns=.680; General Harm=.678; General Overuse=.327). Specific Necessity and Specific Concerns scores were significantly different between medication adherence status groups. CONCLUSIONS: The psychometric properties of the BMQ-T were consistent with those reported in the original study. The BMQ-T was found to be a valid and reliable tool for evaluating beliefs about medicines in patients with Behcet's disease. PMID- 27191775 TI - In situ dispersion of non-aqueous Fe3O4 nanocolloids by microdroplet coalescence and their use in the preparation of magnetic composite particles. AB - Monodispersity and size uniformity are critical issues for nanoparticles, especially for the inorganic particles dispersed in organic carriers serving as the precursor of composites. Herein, for the first time, we have developed a method based on flow-induced droplet coalescence for in situ dispersion of surface-modified Fe3O4 nanoparticles to prepare Fe3O4/polystyrene (Fe3O4/PS) composite particles. A plate-type microchannel was constructed to initiate droplet coalescence for reducing the water-oil interfacial area and for dispersing Fe3O4 nanoparticles into the precursor suspensions. Under optimized conditions, the precursor suspensions could be composed of monodispersed Fe3O4 nanoparticles with an average size of approximately 12 nm. In this case, the saturation magnetization of the prepared superparamagnetic composites was as high as 4.012 emu g(-1) at a magnetite content of 5 wt%. The method is simple and has great potential to be tailored for the preparation of non-aqueous suspensions with uniform and monodispersed nanoparticles. PMID- 27191776 TI - Abstracts of the meeting of the Belgian Society of Endocrinology (5 March 1988). PMID- 27191777 TI - Deployment Experiences, Social Support, and Mental Health: Comparison of Black, White, and Hispanic U.S. Veterans Deployed to Afghanistan and Iraq. AB - Compared to their White counterparts, Black and Hispanic Vietnam-era, male, combat veterans in the United States have experienced discrimination and increased trauma exposure during deployment and exhibited higher rates of postdeployment mental health disorders. The present study examined differences in deployment experiences and postdeployment mental health among male and female Black, Hispanic, and White veterans deployed in support of Operation Enduring Freedom in Afghanistan and Operation Iraqi Freedom in Iraq. Data were drawn from a national survey of veterans (N = 924) who had returned from deployment within the last 2 years. Ethnoracial minority veterans were compared to White veterans of the same gender on deployment experiences and postdeployment mental health. The majority of comparisons did not show significant differences; however, several small group differences did emerge (.02 < eta(2) < .04). Ethnoracial minority veterans reported greater perceived threat in the warzone and more family-related concerns and stressors during deployment than White veterans of the same gender. Minority female veterans reported higher levels of postdeployment symptoms of anxiety than their White counterparts, which were accounted for by differences in deployment experience. These differences call for ongoing monitoring. PMID- 27191778 TI - Legionella pneumophila restrains autophagy by modulating the host's sphingolipid metabolism. AB - Sphingolipids are bioactive molecules playing a key role as membrane components, but they are also central regulators of many intracellular processes including macroautophagy/autophagy. In particular, sphingosine-1-phosphate (S1P) is a critical mediator that controls the balance between sphingolipid-induced autophagy and cell death. S1P levels are adjusted via S1P synthesis, dephosphorylation or degradation, catalyzed by SGPL1 (sphingosine-1-phosphate lyase 1). Intracellular pathogens are able to modulate many different host cell pathways to allow their replication. We have found that infection of eukaryotic cells with the human pathogen Legionella pneumophila triggers a change in the host cell sphingolipid metabolism and specifically affects the levels of sphingosine. Indeed, L. pneumophila secretes a protein highly homologous to eukaryotic SGPL1 (named LpSPL). We solved the crystal structure of LpSPL and showed that it encodes lyase activity, targets the host's sphingolipid metabolism, and plays a role in starvation-induced autophagy during L. pneumophila infection to promote intracellular survival. PMID- 27191779 TI - Commentary on Neodymium-Doped Yttrium Aluminium Garnet Laser Treatment of Pediatric Venous Malformation in the Oral Cavity. PMID- 27191780 TI - Cicatricial Ectropion With Topical 5% Fluorouracil Cream. PMID- 27191781 TI - Reconstruction of a Hand Web Space Defect. PMID- 27191782 TI - Histologic Findings of Tumor Lysis in Advanced Basal Cell Carcinoma Treated With Vismodegib. PMID- 27191784 TI - Pulsed Dye Laser Treatment of Multiple Common Acquired Melanocytic Nevi: A Novel Approach. PMID- 27191783 TI - Laser-Assisted Drug Delivery. AB - BACKGROUND: Laser-assisted drug delivery (LADD) is an evolving new therapy with many possible applications as a highly targeted customizable method for distribution of drugs within the skin. LADD offers the advantages of accessibility, noninvasiveness, compliance, safety, and effectiveness. OBJECTIVE: To review the available literature regarding LADD. METHODS: A MEDLINE search was performed on LADD from 1989 to 2015, and the results are summarized. Practical applications of these procedures are also discussed. RESULTS: Reports of the use of ablative, nonablative, and fractional lasers as a means to increase cutaneous permeation of the topical application of medications and cosmeceuticals were found. The focus of the review was to demonstrate the variety of topical treatments that have been used with the LADD method and the multitude of future studies needed to fully characterize the best application of this evolving technology. CONCLUSION: The most comprehensive review in the literature to date on LADD is provided. Further studies are needed to fully evaluate the safety, dosing, side effects, and results. PMID- 27191785 TI - Advanced Scalp Measurement Using a Phototrichogram With a Protractor and Tapeline. PMID- 27191786 TI - Superficial Acral Fibromyxoma (Digital Fibromyxoma): A Novel Treatment Approach Using Mohs Micrographic Surgery for a Recurrence-Prone Digital Tumor. PMID- 27191788 TI - Occupational safety and health as an element of a complex compensation system evaluation within an organization. AB - Occupational safety and health (OSH) plays a significant role in today's organizations, because it helps in attracting and retaining employees as well as molding their attitudes and behaviors at work. This is why the issue of OSH is stressed in a comprehensive approach to employee rewards: the total reward concept. This article explains how OSH may be included in a complex evaluation process of the compensation system. Although the literature on the effectiveness of employee compensation refers mainly to financial and non-financial components, there is a need for inclusion of working conditions in such analyses. An evaluation of the compensation system that incorporates OSH can drive many benefits for both the organization and employees. Obtaining such benefits, however, requires systematic evaluation of the reward system, including OSH. Incorporation of OSH issue within the comprehensive analysis of compensation systems promotes responsible behavior of all stakeholders. PMID- 27191787 TI - Treatment of genetic defects of thiamine transport and metabolism. AB - INTRODUCTION: Thiamine is a key cofactor for energy metabolism in brain tissue. There are four major genetic defects (SLC19A2, SLC19A3, SLC25A19 and TPK1) involved in the metabolism and transport of thiamine through cellular and mitochondrial membranes. Neurological involvement predominates in three of them (SLC19A3, SCL25A19 and TPK1), whereas patients with SLC19A2 mutations mainly present extra-neurological features (e.g. diabetes mellitus, megaloblastic anaemia and sensori-neural hearing loss). These genetic defects may be amenable to therapeutic intervention with vitamins supplementation and hence, constitutes a main area of research. AREAS COVERED: We conducted a literature review of all reported cases with these genetic defects, and focused our paper on treatment efficacy and safety, adverse effects, dosing and treatment monitoring. Expert commentary: Doses of thiamine vary according to the genetic defect: for SLC19A2, the usual dose is 25-200 mg/day (1-4 mg/kg per day), for SLC19A3, 10-40 mg/kg per day, and for TPK1, 30 mg/kg per day. Thiamine supplementation in SLC19A3-mutated patients restores CSF and intracellular thiamine levels, resulting in successful clinical benefits. In conclusion, evidence collected so far suggests that the administration of thiamine improves outcome in SLC19A-2, SLC19A3- and TPK1 mutated patients, so most efforts should be aimed at early diagnosis of these disorders. PMID- 27191789 TI - Synaptotagmin I's Intrinsically Disordered Region Interacts with Synaptic Vesicle Lipids and Exerts Allosteric Control over C2A. AB - Synaptotagmin I (Syt I) is a vesicle-localized integral membrane protein that senses the calcium ion (Ca(2+)) influx to trigger fast synchronous release of neurotransmitter. How the cytosolic domains of Syt I allosterically communicate to propagate the Ca(2+) binding signal throughout the protein is not well understood. In particular, it is unclear whether the intrinsically disordered region (IDR) between Syt I's transmembrane helix and first C2 domain (C2A) plays an important role in allosteric modulation of Ca(2+) binding. Moreover, the structural propensity of this IDR with respect to membrane lipid composition is unknown. Using differential scanning and isothermal titration calorimetry, we found that inclusion of the IDR does indeed allosterically modulate Ca(2+) binding within the first C2 domain. Additionally through application of nuclear magnetic resonance, we found that Syt I's IDR interacts with membranes whose lipid composition mimics that of a synaptic vesicle. These findings not only indicate that Syt I's IDR plays a role in regulating Syt I's Ca(2+) sensing but also indicate the IDR is exquisitely sensitive to the underlying membrane lipids. The latter observation suggests the IDR is a key route for communication of lipid organization to the adjacent C2 domains. PMID- 27191790 TI - Participatory design facilitates Person Centred Nursing in service improvement with older people: a secondary directed content analysis. AB - AIMS AND OBJECTIVES: To explore, using the example of a project working with older people in an outpatient setting in a large UK NHS Teaching hospital, how the constructs of Person Centred Nursing are reflected in interviews from participants in a Co-design led service improvement project. BACKGROUND: Person Centred Care and Person Centred Nursing are recognised terms in healthcare. Co design (sometimes called participatory design) is an approach that seeks to involve all stakeholders in a creative process to deliver the best result, be this a product, technology or in this case a service. Co-design practice shares some of the underpinning philosophy of Person Centred Nursing and potentially has methods to aid in Person Centred Nursing implementation. RESEARCH DESIGN: The research design was a qualitative secondary Directed analysis. METHODS: Seven interview transcripts from nurses and older people who had participated in a Co design led improvement project in a large teaching hospital were transcribed and analysed. Two researchers analysed the transcripts for codes derived from McCormack & McCance's Person Centred Nursing Framework. RESULTS: The four most expressed codes were as follows: from the pre-requisites: knowing self; from care processes, engagement, working with patient's beliefs and values and shared Decision-making; and from Expected outcomes, involvement in care. This study describes the Co-design theory and practice that the participants responded to in the interviews and look at how the co-design activity facilitated elements of the Person Centred Nursing framework. CONCLUSIONS: This study adds to the rich literature about using emancipatory and transformational approaches to Person Centred Nursing development, and is the first study exploring explicitly the potential contribution of Co-design to this area. IMPLICATIONS FOR PRACTICE: Methods from Co-design allow older people to contribute as equals in a practice development project, co-design methods can facilitate nursing staff to engage meaningfully with older participants and develop a shared understanding and goals. The co-produced outputs of Co-design projects embody and value the expressed beliefs and values of staff and older people. PMID- 27191791 TI - Brain-derived Neurotrophic Factor Signaling Mediates the Antidepressant-like Effect of the Total Flavonoids of Alpiniae Oxyphyllae Fructus in Chronic Unpredictable Mild Stress Mice. AB - The present study verified the antidepressant-like effects of the total flavonoids of Alpinia oxyphylla Miq. (AOF) using the chronic unpredictable mild stresses paradigm and explored the mechanism that underlies antidepressant-like effects of AOF in mice. Previous research has shown that tropomyosin-related kinase B (TrkB) receptor-mediated extracellular regulated protein kinases (ERK) signaling pathways participate in depression pathophysiology. Therefore, we aimed to explore whether AOF improved depression-like behaviors by increasing activity of ERK pathways mediated by TrkB. Results showed that AOF significantly reduced the immobility time in the forced swimming test and increased the sucrose preference in sucrose preference test. In addition, decreased phosphorylated cyclic adenosine monophosphate response element-binding protein (pCREB)/CREB, pERK/ERK, and pTrkB/TrkB levels in the hippocampus induced by chronic unpredictable mild stresses were reversed by intragastric administration of AOF. Results suggested that AOF increased pCREB/CREB, pERK/ERK, and pTrkB/TrkB levels by acting on the TrkB receptor. To verify this hypothesis, mice were pretreated with the TrkB inhibitor K252a (or 0.1% dimethyl sulfoxide, intraperitoneally, 2 weeks), before the intragastric administration of AOF. This resulted in an absence of antidepressant-like effects, as well as no activation of pERK/pCREB/BDNF signaling pathways. Results demonstrated that AOF might exert antidepressant-like effects by targeting TrkB receptor-mediated pERK/pCREB/BDNF signal systems, which could help to identify the AOF receptor. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27191792 TI - Positives and negatives of online dating according to women 50. AB - To understand the positives and negatives of online dating according to the lived experience of older women, telephone interviews were conducted with 45 women ages 50+ who date online. Interviews were audio recorded, transcribed verbatim, and thematically team coded. The opportunity to expand one's social network for both friendships and romantic partners, the ability to control dating risks and pace of relationship formation, and knowing more about one's partner were significant reported benefits of online dating. Dating online also includes unique risks, such as pervasive lying, attempted financial exploitation in the form of scammers, and unwanted electronic sexual aggression. PMID- 27191793 TI - Fabrication of Dendrimer-Based Polyion Complex Submicrometer-Scaled Structures with Enhanced Stability under Physiological Conditions. AB - Submicrometer-scaled (subMU-) self-assembled materials have been developed based on polyion complex (PIC) formation, in particular for biomedical-applications. However, sufficient stability under physiological conditions is required for their practical use. In this study, PIC formation behavior is examined using a block aniomer, poly(ethylene glycol)-b-poly(aspartic acid), and homocatiomers, poly(l-lysine) (LPK) and dendritic poly(l-lysine) (DPK) with different generations, to elucidate the contribution of the dendritic architecture to stability enhancement. LPK-based PIC shows a subMU-vesicular structure only at 25 degrees C in the absence of NaCl; in contrast, DPK-based PIC forms a subMU structure under physiological salt concentration and temperature conditions, even when the number of charges of a single molecule is much smaller than that of LPK. Moreover, the formation of subMU-vesicular and -spherical micellar structures is dependent on DPK generation. Thus, the molecular backbone architecture of the PIC component plays an important role not only in expanding the preparation conditions and enhancing stability, but also in controlling the self-assembled structures, mainly due to the spatially restricted structures of dendrimers. PMID- 27191794 TI - Add-on treatment with intermediate-acting insulin versus sliding-scale insulin for patients with type 2 diabetes or insulin resistance during cyclic glucocorticoid-containing antineoplastic chemotherapy: a randomized crossover study. AB - The aim of this study was to compare the effectiveness and safety of intermediate acting insulin (IMI) titrated on body weight and glucocorticoid dose with that of short-acting sliding-scale insulin (SSI) in patients on recurrent high-dose glucocorticoid-containing chemotherapy. We enrolled 26 patients with type 2 diabetes mellitus or random blood glucose level >12 mmol/l in a previous cycle of chemotherapy in a randomized crossover study. In two consecutive cycles of glucocorticoid-containing chemotherapy, participants were treated with either IMI or SSI, as add-on to routine diabetes medication. We compared time spent in target range (3.9-10 mmol/l), measured by continuous glucose monitoring (CGM), and the occurrence of hypoglycaemia. IMI resulted in a higher proportion of glucose values within target range than SSI (34.4 vs 20.9%; p < 0.001). There were no severe or symptomatic hypoglycaemic events. Two participants in each group had a subclinical hypoglycaemia detected only by CGM. Once-daily IMI resulted in better glycaemic control than SSI in patients with glucocorticoid induced hyperglycaemia during chemotherapy. Safety was not compromised as the incidence of hypoglycaemia was low and not different between both regimens. PMID- 27191795 TI - The Impact of Distraction on Laparoscopic Skills in Veterinary Medical Students. AB - OBJECTIVE: To investigate the impact of distraction on the performance of a simulator-based laparoscopic task in veterinary students. STUDY DESIGN: Prospective, randomized trial. SAMPLE POPULATION: Years 1-4 veterinary students (n=41). METHODS: Participants repeated a simulated laparoscopic peg transfer task to eliminate any learning effects and were subsequently randomized to receive either a cognitive (double-digit addition questions, n=21) or sensory distraction (dogs barking and anesthesia monitor alerts, n=20). The laparoscopic task scores were compared between baseline and in the presence and absence of each distraction. The number of addition questions attempted, and the number of questions answered correctly in 1 minute were compared between baseline and during a concurrent laparoscopic task. RESULTS: Baseline laparoscopic task scores were not significantly different between groups (P=.09). Laparoscopic task scores were significantly lower than baseline when performed with the cognitive distraction (P<.001) and significantly higher than baseline when performed with the sensory distraction (P=.005). Participants undergoing cognitive distraction attempted significantly fewer addition questions (P<.001) and answered significantly fewer addition questions correctly (P<.001) when a concurrent laparoscopic task was performed. CONCLUSION: Cognitive distraction had a negative impact on the performance of a laparoscopic task in this cohort of veterinary students, whereas sensory distraction had a positive effect. PMID- 27191796 TI - Intrathecal Baclofen Therapy in a Child With Severe Scoliosis: Report of 2 Cases. AB - OBJECTIVE: Scoliosis is commonly found in children with cerebral palsy. Many patients with cerebral palsy and scoliosis undergo intrathecal baclofen (ITB) pump placement. The authors report 2 cases with cerebral palsy and severe scoliosis treated with intrathecal baclofen. METHOD: The case of a 7-year-old boy with shunted hydrocephalus required surgical revision of the intrathecal catheter, while the other patient without shunt did not require revision. In the patient with shunted hydrocephalus, after the initial placement of baclofen pump and catheter at Th3 level, spasticity of lower extremities did not improve. The Indium(111) diethylenetriamine pentaacetic acid (In(111) DTPA) scintigraphy with injection of In(111) DTPA through the pump did not demonstrate distribution of the tracer to the lumbosacral area. Conversely, by direct injection of In(111) DTPA through lumbar puncture, the tracer distributed in the whole spinal canal. RESULT: Replacement of the tip of the catheter caudal to the curve of the scoliosis improved the symptom. CONCLUSION: The authors suggest that, in patients with severe scoliosis and shunted hydrocephalus, it may be necessary to place the tip of the catheter caudal to the curve of the scoliosis for correction of spasticity of lower extremities. PMID- 27191797 TI - Outcomes of Ahmed Glaucoma Valve Implantation for Glaucoma Secondary to Fuchs Uveitis Syndrome. AB - PURPOSE: To present the outcomes of Ahmed glaucoma valve implantation (AGV) in glaucoma secondary to Fuchs uveitis syndrome (FUS). METHODS: In this retrospective chart review, two definitions of success were used: 6 mmHg <=intraocular pressure (IOP) <=21 mmHg (success 1), and 6 mmHg <= IOP <=21 mmHg and at least 25% reduction from baseline (success 2). Depending on the need of postoperative antiglaucoma medication, success was defined as either complete or qualified. RESULTS: In total, 17 eyes of 17 patients were included. Complete success rates (both definitions) were 23.5% (n = 17) after 1 year and 23% (n = 13) after 3 years. Qualified success rates (both definitions) were 58.3% (n = 17) after 1 and 38.4% (n = 13) after 3 years. Encapsulated bleb formation was the most common complication (47% of eyes). CONCLUSIONS: AGV was moderately successful in the management of glaucoma secondary to FUS. Success rates are improved by medications, needling, and cycloablative procedures. PMID- 27191798 TI - Phenotypic variability in patients with interstitial 6q21-q22 microdeletion and Acro-Cardio-Facial syndrome. AB - Deletions of 6q are known to be associated with variable clinical phenotypes including facial dysmorphism, hand malformations, heart defects, microcephaly, intellectual disability, epilepsy, and other neurodevelopmental and neuropsychiatric conditions. Here, we report a 7-year-old boy evaluated for facial dysmorphism, trigonocephaly, microcephaly, global developmental delay, and behavioral abnormalities. Molecular karyotyping revealed a 13-Mb deletion within 6q21-q22.31, (chr6:105,771,520-119,130,805; hg19, GRch37) comprising 81 genes. Review of 15 cases with interstitial 6q21-q22.3 deletion from the literature showed that facial dysmorphism, intellectual disability, and corpus callosum abnormalities are the most consistent clinical features in these individuals. Deleted genes and breakpoints in the 6q21-q22 region of the patient reported here are similar to two earlier reported cases with the clinical diagnosis of Acro Cardio-Facial syndrome. However, the present case lacks characteristic clinical findings of Acro-Cardio-Facial syndrome. We discuss, the considerable phenotypic variability seen in individuals with 6q21-q22 microdeletion and emphasize the need for further scrutiny into the hypothesis of Acro-Cardio-Facial syndrome being a microdeletion syndrome. (c) 2016 Wiley Periodicals, Inc. PMID- 27191799 TI - Recovery of episodic memory subprocesses in mild and complicated mild traumatic brain injury at 1 and 12 months post injury. AB - INTRODUCTION: Episodic memory complaints are commonly reported after traumatic brain injury (TBI). The contributions of specific memory subprocesses (encoding, consolidation, and retrieval), however, are not well understood in mild TBI (mTBI). In the present study, we evaluated subprocesses of episodic memory in patients with mTBI using the item-specific deficit approach (ISDA), which analyzes responses on list learning tasks at an item level. We also conducted exploratory analyses to evaluate the effects of complicated mTBI (comp-mTBI) on memory. METHOD: We compared episodic verbal memory performance in mTBI (n = 92) at approximately 1 and 12 months post TBI, as well as in a healthy comparison (HC) group (n = 40) at equivalent time points. Episodic memory was assessed using the California Verbal Learning Test-2nd Edition (CVLT-II), and both standard CVLT II scores and ISDA indices were evaluated. RESULTS: Compared to the HC group, the mTBI group showed significantly poorer encoding and learning across time, as measured by ISDA and CVLT-II. Further analyses of these mTBI subgroups [(noncomplicated mTBI (NC-mTBI, n = 77) and comp-mTBI (n = 15)], indicated that it was the comp-mTBI group who continued to demonstrate poorer encoding ability than the HC group. When the patient groups were directly compared, the NC-mTBI group improved slightly on the ISDA Encoding Deficit Index. While the comp-mTBI group worsened slightly over time, their poorer encoding ability was not likely clinically meaningful. CONCLUSIONS: These findings indicate that, while the NC mTBI and HC groups' performances were comparable by 12 months, a primary, long term deficit in encoding of auditory verbal information remained problematic in the comp-mTBI group. PMID- 27191800 TI - Androgen deprivation therapy use and risk of death in men treated with high-dose radiation for intermediate-risk prostate cancer. PMID- 27191801 TI - Salivary antimicrobial defensins in pregnancy. AB - AIM: Susceptibility to and severity of gingival inflammation are enhanced during pregnancy; however, regulation of oral innate immune response, including antimicrobial peptides, during pregnancy is still unknown. We analysed salivary levels of human beta-defensin (hBD)-1, -2, -3, and human neutrophil peptide (HNP) 1 in pregnant women, and related those to their periodontal status. MATERIAL AND METHODS: In this cohort study, 30 generally healthy, non-smoking Caucasian women without periodontitis were followed at three time points during pregnancy and twice post-partum. The non-pregnant group consisted of 24 women, who were examined three times at the following months. At each visit, periodontal status was recorded and stimulated saliva samples were collected. Salivary estradiol, progesterone, and defensin concentrations were measured by ELISA assays. RESULTS: After adjusting for visible plaque and gingival bleeding, reduced salivary concentrations of hBD-1, hBD-2, and HNP-1 were found especially during the third trimester, whereas hBD-3 concentrations did not change during pregnancy and post partum visits. Weak associations were observed between salivary defensin and hormone concentrations and clinical parameters. CONCLUSION: There seems to be an independent regulation cascade for each antimicrobial defensin in the oral cavity during pregnancy, despite of the similarities between these antimicrobial peptides. PMID- 27191802 TI - Photocatalytic Degradation of Cell Membrane Coatings for Controlled Drug Release. AB - Biomimetic cell-membrane-camouflaged particles with desirable features have been widely used for various biomedical applications. However, there are few reports on employing these particles for cancer drug delivery due to the failure of the membrane coatings to be efficiently degraded in the tumor microenvironment which hampers the drug release. In this work, core-shell SiO2 @TiO2 nanoparticles with enhanced photocatalytic activity are used for controlled degradation of surface erythrocyte membrane coatings. The antitumor drug docetaxel is encapsulated into nanocarriers to demonstrate the controlled drug release under ultraviolet irradiation, and the drug-loaded nanoparticles are further used for enhanced cancer cell therapy. Here, a simple but practical method for degradation of cell membrane coatings is presented, and a good feasibility of using cell membrane coated nanocarriers for controlled drug delivery is demonstrated. PMID- 27191805 TI - Breast Cancer Exosomes Breach the Blood-Brain Barrier. PMID- 27191806 TI - Ready or Not, Here We Go: Decision-Making Strategies From Artificial Intelligence Based on Deep Neural Networks. PMID- 27191807 TI - Hyaluronidase and Hyaluronan Oligosaccharides Promote Neurological Recovery After Intraventricular Hemorrhage. PMID- 27191808 TI - Increasing the Relevance of Optogenetics to the Human Brain: Novel Platform for Nonhuman Primates. PMID- 27191809 TI - Targeted Treatment of Experimental Spinal Cord Glioma With Dual Gene-Engineered Human Neural Stem Cells. PMID- 27191810 TI - Iatrogenic Alzheimer Disease? Amyloid-beta Protein Transmission Between Humans. PMID- 27191811 TI - The FIRST Trial: Implications for Neurosurgery. PMID- 27191812 TI - Epidural Spinal Cord Stimulation for the Restoration of Balance and Gait Following Spinal Cord Injury. PMID- 27191813 TI - Isocitrate Dehydrogenase Mutation Leads to Alteration in 3-Dimensional DNA Structure and Oncogene Activation in Gliomas. PMID- 27191814 TI - Targeting MicroRNA to Enhance Poststroke Recovery. PMID- 27191816 TI - Nicotiana benthamiana MAPK-WRKY pathway confers resistance to a necrotrophic pathogen Botrytis cinerea. AB - MEK2-SIPK/WIPK cascade, a Nicotiana benthamiana mitogen-activated protein kinase (MAPK) cascade, is an essential signaling pathway for plant immunity and involved in hypersensitive response (HR) accompanied by cell death. WRKY transcription factors as substrates of SIPK and WIPK have been isolated and implicated in HR cell death. Here, we show virus-induced gene silencing of WRKY genes compromised constitutively active MEK2-triggered cell death in N. benthamiana leaves. In general, HR cell death enhances susceptibility to necrotrophic pathogens such as Botrytis cinerea. However, the WRKY gene silencing elevated susceptibility to B. cinerea. These findings suggest that downstream WRKYs of MEK2-SIPK/WIPK cascade are required for cell death-dependent and -independent immunities in N. benthamiana. PMID- 27191817 TI - Effects of Ecballium Elaterium on Proinflammatory Cytokines in a Rat Model of Sepsis. AB - OBJECTIVE: Ecballium elaterium (EE) is a plant from Cucurbitaceae family. Its anti-inflammatory role in sepsis is not well understood. We investigated the effects of EE on serum levels of proinflammatory cytokines and further explored the mechanisms underlying histological changes in liver and ileum following EE administration in a polymicrobial sepsis model. METHODS: Thirty rats were divided into three groups of 10 rats each. Rats were subjected to sham laparotomy plus normal saline administration (control group, CG), laparotomy with cecal ligation and puncture (CLP) (sepsis group, SG), and laparotomy with CLP plus 2.5 mg/kg EE administration (experimental group, EG). Twenty-four hours after laparotomy, animals underwent cardiac puncture, and blood was collected for interleukin 1 (IL 1), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) assessment. Whole sections of liver and ileum tissues were collected for histologic examination. RESULTS: The serum level of IL-6 was significantly lower in EG as compared to SG. Although IL-6 levels were shown a statistically significant (p < 0.0001) decline to near control values, no significant changes were observed in serum levels of IL-1 and TNF-alpha after EE treatment. Histologic examination revealed statistically significant reduction in collagen formation (p = 0.001) on serosal surface of ileum and hepatic venous congestion (p = 0.040) in EG as compared to SG. CONCLUSION: EE might play a protective role in sepsis prevention and treatment by decreasing IL-6 production and reducing liver damage and may influence bacterial translocation by reinforcing intestinal barrier function. PMID- 27191819 TI - Macroscopic Alignment of One-Dimensional Conjugated Polymer Nanocrystallites for High-Mobility Organic Field-Effect Transistors. AB - Controlling the morphology of polymer semiconductors remains a fundamental challenge that hinders their widespread applications in electronic and optoelectronic devices and commercial feasibility. Although conjugated polymer nanowires (NWs) are envisioned to afford high charge-carrier mobility, the alignment of preformed conjugated polymer NWs has not been reported. Here, we demonstrate an extremely simple and effective strategy to generate well-aligned arrays of one-dimensional (1D) polymer semiconductors that exhibit remarkable enhancement in charge transport using a solution shear-coating technique. We show that solution shear coating of poly(alkylthiophene) NWs induces extension or coplanarization of the polymer backbone and highly aligned network films, which results in enhanced intra- and intermolecular ordering and reduced grain boundaries. Consequently, highly aligned poly(3-hexylthiophene) NWs exhibited over 33-fold enhancement in the average carrier mobility, with the highest mobility of 0.32 cm(2) V(-1) s(-1) compared to pristine films. The presented platform is a promising strategy and general approach for achieving well-aligned 1D nanostructures of polymer semiconductors and could enable the next generation of high-performance flexible electronic devices for a wide range of applications. PMID- 27191818 TI - Debate Regarding Oseltamivir Use for Seasonal and Pandemic Influenza. AB - A debate about the market-leading influenza antiviral medication, oseltamivir, which initially focused on treatment for generally mild illness, has been expanded to question the wisdom of stockpiling for use in future influenza pandemics. Although randomized controlled trial evidence confirms that oseltamivir will reduce symptom duration by 17-25 hours among otherwise healthy adolescents and adults with community-managed disease, no randomized controlled trials have examined the effectiveness of oseltamivir against more serious outcomes. Observational studies, although criticized on methodologic grounds, suggest that oseltamivir given early can reduce the risk for death by half among persons hospitalized with confirmed infection caused by influenza A(H1N1)pdm09 and influenza A(H5N1) viruses. However, available randomized controlled trial data may not be able to capture the effect of oseltamivir use among hospitalized patients with severe disease. We assert that data on outpatients with relatively mild disease should not form the basis for policies on the management of more severe disease. PMID- 27191821 TI - Fully Automated RNAscope In Situ Hybridization Assays for Formalin-Fixed Paraffin Embedded Cells and Tissues. AB - Biomarkers such as DNA, RNA, and protein are powerful tools in clinical diagnostics and therapeutic development for many diseases. Identifying RNA expression at the single cell level within the morphological context by RNA in situ hybridization provides a great deal of information on gene expression changes over conventional techniques that analyze bulk tissue, yet widespread use of this technique in the clinical setting has been hampered by the dearth of automated RNA ISH assays. Here we present an automated version of the RNA ISH technology RNAscope that is adaptable to multiple automation platforms. The automated RNAscope assay yields a high signal-to-noise ratio with little to no background staining and results comparable to the manual assay. In addition, the automated duplex RNAscope assay was able to detect two biomarkers simultaneously. Lastly, assay consistency and reproducibility were confirmed by quantification of TATA-box binding protein (TBP) mRNA signals across multiple lots and multiple experiments. Taken together, the data presented in this study demonstrate that the automated RNAscope technology is a high performance RNA ISH assay with broad applicability in biomarker research and diagnostic assay development. J. Cell. Biochem. 117: 2201-2208, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27191820 TI - Structural domains within the HIV-1 mRNA and the ribosomal protein S25 influence cap-independent translation initiation. AB - The 5' leader of the HIV-1 genomic RNA is a multifunctional region that folds into secondary/tertiary structures that regulate multiple processes during viral replication including translation initiation. In this work, we examine the internal ribosome entry site (IRES) located in the 5' leader that drives translation initiation of the viral Gag protein under conditions that hinder cap dependent translation initiation. We show that activity of the HIV-1 IRES relies on ribosomal protein S25 (eS25). Additionally, a mechanistic and mutational analysis revealed that the HIV-1 IRES is modular in nature and that once the 40S ribosomal subunit is recruited to the IRES, translation initiates without the need of ribosome scanning. These findings elucidate a mechanism of initiation by the HIV-1 IRES whereby a number of highly structured sites present within the HIV 1 5' leader leads to the recruitment of the 40S subunit directly at the site of initiation of protein synthesis. PMID- 27191822 TI - Increased Ocular Levels of MicroRNA-148a in Cases of Retinal Detachment Promote Epithelial-Mesenchymal Transition. AB - PURPOSE: The purpose of this study was to determine microRNA expression in vitreous and subretinal fluid (SRF) samples from patients with retinal detachment (RD). The pathological importance of the identified microRNA transcript levels was analyzed in vitro. METHODS: Vitreous fluid was collected from 10 patients with macular hole (MH), vitreomacular traction syndrome (VMTS), or foveoschisis and from 11 patients with RD. Subretinal fluid was collected from 7 patients with RD. Of these, blood serum was collected in 4 patients. MicroRNA microarray profiling was performed to identify microRNA transcripts that were present in vitreous fluid, and more redundantly detected in SRF, of patients with RD, but not detected in control eyes. Western blotting and scratch assays were performed in ARPE-19 cells and primary human RPE cell lines transfected with microRNA to elucidate the effect of identified microRNA transcripts on epithelial-mesenchymal transition (EMT). RESULTS: MicroRNA microarray profiling revealed that hsa-miR 148a-3p was the most redundantly detected transcript in SRF and vitreous fluid from patients with RD, but not those with the other diseases. Expression levels of hsa-miR-148a-3p were higher in SRF samples than in blood serum samples in 3 out of 4 patients. Following hsa-miR-148a-3p mimic transfection, ARPE-19 and human RPE cells demonstrated increased expression of alpha-smooth muscle actin by Western blotting and increased migration ability during scratch assays. CONCLUSIONS: The results of the present study indicate that hsa-miR-148a-3p was specifically detected in RD and promotes EMT in RPE. PMID- 27191824 TI - Treatment Options for Veterans With Posttraumatic Stress Disorder-Reply. PMID- 27191825 TI - Efficiency of the Switching Process in Organic Electrochemical Transistors. AB - Entirely screen printed organic electrochemical transistors (OECTs) based on poly(3,4-ethylenedioxithiophene) poly(styrenesulfonate) ( PEDOT: PSS) and a polymer electrolyte are investigated in view of a correlation between the electrical charge consumed during switching and the volume of PEDOT: PSS in the transistor channel. An understanding of the relation between charge consumption and the amount of electrochemically active PEDOT is essential for the design of high performance transistors and for providing a deeper insight into the fundamentals of the electrochemical switching process in OECTs. It turned out that a precise control of the width of the PEDOT: PSS source-drain line is imperative for maximizing both the on-current and the on/off current ratio of lateral OECTs. PMID- 27191823 TI - Progressive Early Breakdown of Retinal Pigment Epithelium Function in Hyperglycemic Rats. AB - PURPOSE: Diabetic macular edema (DME), an accumulation of fluid in the subretinal space, is a significant cause of vision loss. The impact of diabetes on the breakdown of the inner blood-retina barrier (BRB) is an established event that leads to DME. However, the role of the outer BRB in ocular diabetes has received limited attention. We present evidence that the breakdown of normal RPE function in hyperglycemia facilitates conditions conducive to DME pathogenesis. METHODS: Brown Norway rats (130-150 g) were injected intraperitoneally with streptozotocin (STZ; 60 mg/kg) to induce hyperglycemia. After 4 weeks, Evans blue (EB) dye was injected intravenously to determine whether there was leakage of albumin into the retina. Subretinal saline blebs (0.5-1 MUL) were placed 4 and 9 weeks after STZ injection, and time-lapse optical coherence tomography tracked the resorption rate. In a subset of rats, intravitreal bevacizumab, a humanized monoclonal antibody targeted to VEGF, was given at 5 weeks and resorption was measured at 9 weeks. RESULTS: The ability of the RPE to transport fluid was reduced significantly after 4 and 9 weeks of hyperglycemia with a reduction of over 67% at 9 weeks. No EB dye leakage from inner retinal vessels was measured in hyperglycemic animals compared to control. The intravitreal administration of bevacizumab at week 5 significantly increased the rate of fluid transport in rats subjected to hyperglycemia for 9 weeks. CONCLUSIONS: These results demonstrate that chronic hyperglycemia altered RPE fluid transport, in part dependent on the actions of VEGF. These results support the idea that RPE dysfunction is an early event associated with hyperglycemia that contributes to fluid accumulation in DME. PMID- 27191826 TI - Synthesis and Evaluation of 1-Substituted-Biguanide Derivatives as Anti-Diabetic Agents for Type II Diabetes Insulin Resistant. AB - New 1-substituted-biguanide derivatives 1-3 were synthesized by the reaction of 2,4-dimethoxyaniline, hydrazine and methylhydrazine with dicyandiamide in diluted hydrochloric acid. The resulting biguanide salts were fully characterized by spectroscopic methods. The synthesized compounds were screened for their anti diabetic activity with standard metformin drug. Oral treatment of hyperglycemic rats with the synthesized biguanide derivatives (200 mg/kg/day) for 2 weeks significantly decreased the elevated blood glucose level. Oral administration of biguanide derivative 2 significantly decreased the level of total cholesterol. While, the triglycerides level was little decreased following administration of biguanide 1 as compared to hyperglycemic rats. Additionally, anti-diabetic properties towards liver function enzyme activities (AST and ALT) and kidney functions (urea and critinine) as well as histopathological studies relative to metformin hydrochloride were investigated and discussed. PMID- 27191827 TI - Molecular dynamics simulation of d-Benzedrine transmitting through molecular channels within D3R. AB - Dex-Benzedrine (known as d-Benzedrine or SAT) acts in dopamine receptors of central nerve cell system. In clinic, SAT is used to treat a variety of diseases; meanwhile, it has dependence and addiction. In order to investigate the pharmacology and addiction mechanisms of SAT as a medicine, in this paper, we have studied the structure of D3R complex protein with SAT, and based on which, using potential mean force with umbrella samplings and the simulated phospholipid bilayer membrane (or POPC bilayer membrane), the molecular dynamics simulation was performed to obtain free energy changes upon the trajectories for SAT moving along the molecular channels within D3R. The free energy change for SAT transmitting toward the outside of cell along the functional molecular channel within D3R is 83.5 kJ mol-1. The change of free energy for SAT to permeate into the POPC bilayer membrane along the protective molecular channel within D3R is 87.7 kJ mol-1. Our previous work gave that the free energy for Levo-Benzedrine (RAT) transmitting toward the outside of cell along the functional molecular channel within D3R is 91.4 kJ mol-1, while it is 117.7 kJ mol-1 for RAT to permeate into the POPC bilayer membrane along the protective molecular channel within D3R. The values of free energy suggest that SAT relatively prefers likely to pass through the functional molecular channel within D3R for increasing the release of dopamine molecules resulting in a variety of functional effects for SAT. The obtained results show that the pharmacology and addiction mechanisms of SAT as a drug are closely related to the molecular dynamics and mechanism for SAT transmitting along molecular channels within D3R. PMID- 27191828 TI - Motivational Interviewing: Creating a Leadership Role for Social Work in the Era of Healthcare Reform. AB - To better address the needs of individuals with a range of complex health conditions, the Affordable Care Act has shifted the focus from acute care to prevention through behavior change and promoted the integration of physical and behavioral healthcare systems. Central to healthcare reform is delivering person centered care, which means actively engaging people in their treatment decisions and managing their wellness. Motivational Interviewing (MI) is perhaps the most widely used intervention to promote behavior change. Although MI is utilized across most health disciplines, social workers are uniquely positioned to lead dissemination and on-going training efforts in this area. PMID- 27191831 TI - Parental Serotonin Transporter Polymorphism (5-HTTLPR) Moderates Associations of Stress and Child Behavior With Parenting Behavior. AB - The serotonin transporter-linked polymorphic region (5-HTTLPR) is associated with caregiving in nonhuman animals and with affective and cognitive correlates of human parenting, yet its association with human parenting is largely unknown. Using a well-characterized sample of parents and offspring, we evaluated the association of parental 5-HTTLPR with observed positive and negative parenting behavior, as well as its biologically plausible moderation of child-related stress and disruptive child behavior as predictors of parenting. One hundred and sixty-two parents (86% mothers) and their 6- to 9-year-old children with and without attention-deficit/hyperactivity disorder were ascertained using multiple methods including structured interviews, rating scales, and observed parent-child interaction, yielding strong measures of key constructs. Controlling for multiple youth-level (e.g., sex, 5-HTTLPR genotype, disruptive behavior) and parent-level (e.g., demographics, depression, attention-deficit/hyperactivity disorder) factors, parents with an S allele exhibited significantly less observed positive parenting than those with the LL genotype. Significant Gene * Environment interactions were also observed: Child-related stress was negatively associated with observed parental negativity among SS/SL genotype parents but not LL genotype parents; next, observed disruptive child behavior was positively associated with parental negativity for both genotypes, but the effect was strongest in SS/SL parents. These preliminary findings suggest that parental 5 HTTLPR is uniquely associated with positive and negative parenting behavior, with more specific patterns according to child-related stress and disruptive child behavior. We consider implications for future research evaluating genetic influences on parenting as well as considerations for designing and delivering parenting-based interventions. PMID- 27191830 TI - Seeing Is Believing: Evaluating a Point-of-Care Ultrasound Curriculum for 1st Year Medical Students. AB - PROBLEM: Point-of-care ultrasound has been a novel addition to undergraduate medical education at a few medical schools. The impact is not fully understood, and few rigorous assessments of educational outcomes exist. This study assessed the impact of a point-of-care ultrasound curriculum on image acquisition, interpretation, and student and faculty perceptions of the course. INTERVENTION: All 142 first-year medical students completed a curriculum on ultrasound physics and instrumentation, cardiac, thoracic, and abdominal imaging. A flipped classroom model of preclass tutorials and tests augmenting live, hands-on scanning sessions was incorporated into the physical examination course. Students and faculty completed surveys on impressions of the curriculum, and all students under-went competency assessments with standardized patients. CONTEXT: The curriculum was a mandatory part of the physical examination course and was taught by experienced clinician-sonographers as well as faculty who do not routinely perform sonography in their clinical practice. OUTCOME: Students and faculty agreed that the physical examination course was the right time to introduce ultrasound (87% and 80%). Students demonstrated proper use of the ultrasound machine functions (M score = 91.55), and cardiac, thoracic, and abdominal system assessments (M score = 80.35, 79.58, and 71.57, respectively). Students and faculty valued the curriculum, and students demonstrated basic competency in performance and interpretation of ultrasound. Further study is needed to determine how to best incorporate this emerging technology into a robust learning experience for medical students. PMID- 27191829 TI - Batf3-dependent CD103(+) dendritic cell accumulation is dispensable for mucosal and systemic antifungal host defense. AB - Dendritic cells (DCs) are critical for defense against a variety of pathogens and the formation of adaptive immune responses. The transcription factor Batf3 is critical for the development of CD103(+)CD11b(-) DCs, which promote IL-12 dependent protective immunity during viral and parasitic infections, dampen Th2 immunity during helminthic infection, and exert detrimental effects during bacterial infection. Whether CD103(+) DCs modulate immunity during systemic or mucosal fungal disease remains unknown. Herein, we report that Batf3 is critical for accumulation of CD103(+) DCs in the kidney and tongue at steady state, for their expansion during systemic and oropharyngeal candidiasis, and for tissue specific production of IL-12 in kidney but not tongue during systemic and oropharyngeal candidiasis, respectively. Importantly, deficiency of CD103(+) DCs does not impair survival or fungal clearance during systemic or oropharyngeal candidiasis, indicating that Batf3-dependent CD103(+) DC accumulation mediates pathogen- and tissue-specific immune effects. PMID- 27191832 TI - One-Way Multishape-Memory Effect and Tunable Two-Way Shape Memory Effect of Ionomer Poly(ethylene-co-methacrylic acid). AB - Reversible elongation by cooling and contraction by heating, without the need for repeated programming, is well-known as the two-way shape-memory effect (2W-SME). This behavior is contrary to the common physics-contraction when cooling and expansion when heating. Materials with such behavior may find many applications in real life, such as self-sufficient grippers, fastening devices, optical gratings, soft actuators, and sealant. Here, it is shown that ionomer Surlyn 8940, a 50-year old polymer, exhibits both one-way multishape-memory effects and tunable two-way reversible actuation. The required external tensile stress to trigger the tunable 2W-SME is very low when randomly jumping the temperatures within the melting transition window. With a proper one-time programming, "true" 2W-SME (i.e., 2W-SME without the need for an external tensile load) is also achieved. A long training process is not needed to trigger the tunable 2W-SME. Instead, a proper one-time tensile programming is sufficient to trigger repeated and tunable 2W-SME. Because the 2W-SME of the ionomer Surlyn is driven by the thermally reversible network, here crystallization and melting transitions of the semicrystalline poly(ethylene-co-methacrylic acid), it is believed that a class of thermally reversible polymers should also exhibit tunable 2W-SMEs. PMID- 27191833 TI - Calcium and filoviruses: a budding relationship. PMID- 27191835 TI - Synthesis of Esters by in Situ Formation and Trapping of Diazoalkanes. AB - A general method has been developed for the in situ formation and trapping of diazoalkanes by carboxylic acids to form esters. The method is applicable to a large variety of carboxylic acids using diazo compounds that are formed from the hydrazones of benzaldehydes and aryl ketones. In situ reaction monitoring with IR spectroscopy (ReactIR) was used to demonstrate that slow addition of the hydrazone to a mixture of oxidant and carboxylic acid avoids the buildup of the diazo compound. This method enables the safe preparation of esters from simple precursors without isolation of diazo compounds. PMID- 27191834 TI - Human Adenovirus Associated with Severe Respiratory Infection, Oregon, USA, 2013 2014. AB - Several human adenoviruses (HAdVs) can cause respiratory infections, some severe. HAdV-B7, which can cause severe respiratory disease, has not been recently reported in the United States but is reemerging in Asia. During October 2013-July 2014, Oregon health authorities identified 198 persons with respiratory symptoms and an HAdV-positive respiratory tract specimen. Among 136 (69%) hospitalized persons, 31% were admitted to the intensive care unit and 18% required mechanical ventilation; 5 patients died. Molecular typing of 109 specimens showed that most (59%) were HAdV-B7, followed by HAdVs-C1, -C2, -C5 (26%); HAdVs-B3, -B21 (15%); and HAdV-E4 (1%). Molecular analysis of 7 HAdV-B7 isolates identified the virus as genome type d, a strain previously identified only among strains circulating in Asia. Patients with HAdV-B7 were significantly more likely than those without HAdV-B7 to be adults and to have longer hospital stays. HAdV-B7 might be reemerging in the United States, and clinicians should consider HAdV in persons with severe respiratory infection. PMID- 27191836 TI - Programmatic Efforts at the National Institutes of Health to Promote and Support the Careers of Women in Biomedical Science. AB - Although women have reached parity at the training level in the biological sciences and medicine, they are still significantly underrepresented in the professoriate and in mid- and senior-level life science positions. Considerable effort has been devoted by individuals and organizations across science sectors to understanding this disparity and to developing interventions in support of women's career development. The National Institutes of Health (NIH) formed the Office of Research on Women's Health (ORWH) in 1990 with the goals of supporting initiatives to improve women's health and providing opportunities and support for the recruitment, retention, reentry, and sustained advancement of women in biomedical careers. Here, the authors review several accomplishments and flagship activities initiated by the NIH and ORWH in support of women's career development during this time. These include programming to support researchers returning to the workforce after a period away (Research Supplements to Promote Reentry into Biomedical and Behavioral Research Careers), career development awards made through the Building Interdisciplinary Research Careers in Women's Health program, and trans-NIH involvement and activities stemming from the NIH Working Group on Women in Biomedical Careers. These innovative programs have contributed to advancement of women by supporting the professional and personal needs of women in science. The authors discuss the unique opportunities that accompany NIH partnerships with the scientific community, and conclude with a summary of the impact of these programs on women in science. PMID- 27191837 TI - Quality of Care Provided by Board-Certified Versus Non-Board-Certified Psychiatrists and Neurologists. AB - PURPOSE: To examine associations between board certification of psychiatrists and neurologists and quality-of-care measures, using multilevel models controlling for physician and patient characteristics, and to assess feasibility of linking physician information with patient records to construct quality measures from electronic claims data. METHOD: The authors identified quality measures and matched claims data from 2006 to 2012 with 942 board-certified (BC) psychiatrists, 868 non-board-certified (nBC) psychiatrists, 963 BC neurologists, and 328 nBC neurologists. Using the matched data, they identified psychiatrists who treated at least one patient with a schizophrenia diagnosis, and neurologists attending patients discharged with a principal diagnosis of ischemic stroke, and analyzed claims from these patients. For patients with schizophrenia who were prescribed an atypical antipsychotic, quality measures were claims for glucose and lipid tests, duration of any antipsychotic treatment, and concurrent prescription of multiple antipsychotics. For patients with ischemic stroke, quality measures were dysphagia evaluation; speech/language evaluation; and prescription of clopidogrel, low-molecular-weight heparin, intravenous heparin, and warfarin (for patients with co-occurring atrial fibrillation). RESULTS: Overall, multilevel models (patients nested within physicians) showed no statistically significant differences in quality measures between BC and nBC psychiatrists and neurologists. CONCLUSIONS: The authors demonstrated the feasibility of linking physician information with patient records to construct quality measures from electronic claims data, but there may be only minimal differences in the quality of care between BC and nBC psychiatrists and neurologists, or there may be a difference that could not be measured with the quality measures used. PMID- 27191838 TI - Strategies for Developing and Recognizing Faculty Working in Quality Improvement and Patient Safety. AB - Academic clinical departments have the opportunity and responsibility to improve the quality and value of care and patient safety by supporting effective quality improvement activities. The pressure to provide high-value care while further developing academic programs has increased the complexity of decision making and change management in academic health systems. Overcoming these challenges will require faculty engagement and leadership; however, most academic departments do not have a sufficient number of individuals with expertise and experience in quality improvement and patient safety (QI/PS). Accordingly, the authors of this article advocate for a targeted and proactive approach to developing faculty working in QI/PS. They propose a strategy predicated on the identification of QI/PS as a strategic priority for academic departments, the creation of enabling resources in QI/PS, and the expansion of rigorous training programs in change management and in improvement and implementation sciences. Professional organizations, health systems, medical schools, and academic departments should recognize successful QI/PS work with awards and promotions. Individual faculty members should expand their collaborative networks, consider the generalizability and scholarly impact of their efforts when designing QI/PS initiatives, and benchmark the outcomes of their performance. Appointments and promotions committees should work proactively with department and QI/PS leaders to ensure that outstanding achievement in QI/PS is defined and recognized. As with the development of physician-investigators and clinician-educators, departments and health systems need a comprehensive approach to support and recognize the contributions of faculty working in QI/PS to meet the considerable needs and opportunities in health care. PMID- 27191839 TI - Five Tactics to Quickly Build Quality Improvement and Patient Safety Capacity at Academic Health Centers. AB - In this issue, Coleman and colleagues propose an ambitious strategic action framework for academic health center (AHC) department chairs seeking to expand faculty expertise in quality improvement and patient safety (QI/PS). Noting the advent of value-based payment models and that AHCs lag behind some community hospitals in QI/PS, Coleman and colleagues call for deliberate, proactive faculty development and recognition measures to build QI/PS capacity at AHCs. In this Invited Commentary, the author addresses the five challenges to strengthening QI/PS capacity identified by Coleman and colleagues: (1) the mentorship gap: the paucity of expert senior faculty who can mentor junior colleagues in QI/PS; (2) data and analytic bottlenecks: information systems and analytic requests to support QI/PS projects often get pushed to the back of long queues of prioritized queries from other departments, effectively halting QI/PS projects; (3) misalignment between existing reimbursement mechanisms and QI/PS: current fee-for service and prospective payment mechanisms drive high utilization of costly interventions and can financially penalize organizations that keep patients well and avoid interventions; (4) limited recognition for QI/PS achievement in academic advancement decisions; and (5) pressure to invent and deploy alternative business models that reward value and results rather than the volume and pricing of services, to better align payer, provider, and patient incentives around high value care. The author outlines practical short-term measures to mitigate the first four challenges and a more expansive vision for AHCs to transform their business models and regain a leadership position in QI/PS to address the fifth challenge. PMID- 27191840 TI - Microanalytic Assessment of Self-Regulated Learning During Clinical Reasoning Tasks: Recent Developments and Next Steps. AB - Helping medical educators obtain and use assessment data to assist medical students, residents, and physicians in reducing diagnostic errors and other forms of ineffective clinical practice is of critical importance. Self-Regulated Learning-Microanalytic Assessment and Training is an assessment-to-intervention framework designed to address this need by generating data about trainees' strategic processes (e.g., focusing on clinical task procedures), regulatory processes (e.g., planning how to do a task), and motivational processes (e.g., increasing confidence for performing a task) as they perform clinical activities. In this article, the authors review several studies that have used an innovative assessment approach, called self-regulated learning (SRL) microanalysis, to generate data about how trainees regulate their thinking and actions during clinical reasoning tasks. Across the studies, initial findings revealed that medical students often do not exhibit strategic thinking and action during clinical reasoning practice tasks even though some regulatory processes (e.g., planning) are predictive of important medical education outcomes. Further, trainees' motivation beliefs, strategic thinking, and self-evaluative judgments tend to shift rapidly during clinical skills practice and may also vary across different parts of a patient encounter. Collectively, these findings underscore the value of dynamically assessing trainees' SRL as they complete clinical tasks. The findings also set the stage for exploring how medical educators can best use SRL microanalytic assessment data to guide remedial practices and the provision of feedback to trainees. Implications and future research directions for connecting assessments to intervention in medical education are discussed. PMID- 27191842 TI - Coached Peer Review: Developing the Next Generation of Authors. AB - PROBLEM: Publishing in academic journals is challenging for learners. Those who pass the initial stages of internal review by an editor often find the anonymous peer review process harsh. Academic blogs offer alternate avenues for publishing medical education material. Many blogs, however, lack a peer review process, which some consumers argue compromises the quality of materials published. APPROACH: CanadiEM (formerly BoringEM) is an academic educational emergency medicine blog dedicated to publishing high-quality materials produced by learners (i.e., residents and medical students). The editorial team has designed and implemented a collaborative "coached peer review" process that comprises an open exchange among the learner-author, editors, and reviewers. The goal of this process is to facilitate the publication of high-quality academic materials by learner-authors while providing focused feedback to help them develop academic writing skills. OUTCOMES: The authors of this Innovation Report surveyed (February-June 2015) their blog's learner-authors and external expert "staff" reviewers who had participated in coached peer review for their reactions to the process. The survey results revealed that participants viewed the process positively compared with both traditional journal peer review and academic blog publication processes. Participants found the process friendly, easy, efficient, and transparent. Learner-authors also reported increased confidence in their published material. These outcomes met the goals of coached peer review. NEXT STEPS: CanadiEM aims to inspire continued participation in, exposure to, and high quality production of academic writing by promoting the adoption of coached peer review for online educational resources produced by learners. PMID- 27191841 TI - Role Modeling and Regional Health Care Intensity: U.S. Medical Student Attitudes Toward and Experiences With Cost-Conscious Care. AB - PURPOSE: To examine medical student attitudes toward cost-conscious care and whether regional health care intensity is associated with reported exposure to physician role-modeling behaviors related to cost-conscious care. METHOD: Students at 10 U.S. medical schools were surveyed in 2015. Thirty-five items assessed attitudes toward, perceived barriers to and consequences of, and observed physician role-modeling behaviors related to cost-conscious care (using scales for cost-conscious and potentially wasteful behaviors; Cronbach alphas of 0.82 and 0.81, respectively). Regional health care intensity was measured using Dartmouth Atlas End-of-Life Chronic Illness Care data: ratio of physician visits per decedent compared with the U.S. average, ratio of specialty to primary care physician visits per decedent, and hospital care intensity index. RESULTS: Of 5,992 students invited, 3,395 (57%) responded. Ninety percent (2,640/2,932) agreed physicians have a responsibility to contain costs. However, 48% (1,1416/2,960) thought ordering a test is easier than explaining why it is unnecessary, and 58% (1,685/2,928) agreed ordering fewer tests will increase the risk of malpractice litigation. In adjusted linear regression analyses, students in higher-health-care-intensity regions reported observing significantly fewer cost-conscious role-modeling behaviors: For each one-unit increase in the three health care intensity measures, scores on the 21-point cost-conscious role modeling scale decreased by 4.4 (SE 0.7), 3.2 (0.6), and 3.9 (0.6) points, respectively (all P < .001). CONCLUSIONS: Medical students endorse barriers to cost-conscious care and encounter conflicting role-modeling behaviors, which are related to regional health care intensity. Enhancing role modeling in the learning environment may help prepare future physicians to address health care costs. PMID- 27191844 TI - Cysteine Peptidase B Regulates Leishmania mexicana Virulence through the Modulation of GP63 Expression. AB - Cysteine peptidases play a central role in the biology of Leishmania. In this work, we sought to further elucidate the mechanism(s) by which the cysteine peptidase CPB contributes to L. mexicana virulence and whether CPB participates in the formation of large communal parasitophorous vacuoles induced by these parasites. We initially examined the impact of L. mexicana infection on the trafficking of VAMP3 and VAMP8, two endocytic SNARE proteins associated with phagolysosome biogenesis and function. Using a CPB-deficient mutant, we found that both VAMP3 and VAMP8 were down-modulated in a CPB-dependent manner. We also discovered that expression of the virulence-associated GPI-anchored metalloprotease GP63 was inhibited in the absence of CPB. Expression of GP63 in the CPB-deficient mutant was sufficient to down-modulate VAMP3 and VAMP8. Similarly, episomal expression of GP63 enabled the CPB-deficient mutant to establish infection in macrophages, induce the formation of large communal parasitophorous vacuoles, and cause lesions in mice. These findings implicate CPB in the regulation of GP63 expression and provide evidence that both GP63 and CPB are key virulence factors in L. mexicana. PMID- 27191845 TI - Infant Cries Rattle Adult Cognition. AB - The attention-grabbing quality of the infant cry is well recognized, but how the emotional valence of infant vocal signals affects adult cognition and cortical activity has heretofore been unknown. We examined the effects of two contrasting infant vocalizations (cries vs. laughs) on adult performance on a Stroop task using a cross-modal distraction paradigm in which infant distractors were vocal and targets were visual. Infant vocalizations were presented before (Experiment 1) or during each Stroop trial (Experiment 2). To evaluate the influence of infant vocalizations on cognitive control, neural responses to the Stroop task were obtained by measuring electroencephalography (EEG) and event-related potentials (ERPs) in Experiment 1. Based on the previously demonstrated existence of negative arousal bias, we hypothesized that cry vocalizations would be more distracting and invoke greater conflict processing than laugh vocalizations. Similarly, we expected participants to have greater difficulty shifting attention from the vocal distractors to the target task after hearing cries vs. after hearing laughs. Behavioral results from both experiments showed a cry interference effect, in which task performance was slower with cry than with laugh distractors. Electrophysiology data further revealed that cries more than laughs reduced attention to the task (smaller P200) and increased conflict processing (larger N450), albeit differently for incongruent and congruent trials. Results from a correlation analysis showed that the amplitudes of P200 and N450 were inversely related, suggesting a reciprocal relationship between attention and conflict processing. The findings suggest that cognitive control processes contribute to an attention bias to infant signals, which is modulated in part by the valence of the infant vocalization and the demands of the cognitive task. The findings thus support the notion that infant cries elicit a negative arousal bias that is distracting; they also identify, for the first time, the neural dynamics underlying the unique influence that infant cries and laughs have on cognitive control. PMID- 27191847 TI - Cortisol Awakening Response and Walking Speed in Older People. AB - In older people, less diurnal variability in cortisol levels has been consistently related to worse physical performance, especially to slower walking speed (WS). The cortisol awakening response (CAR) is a discrete component of the hypothalamic-pituitary-adrenal axis that has been related to several health problems, such as cardiovascular disease and/or worse performance on executive function and memory. The relationship between the CAR and physical performance in older people is poorly understood. In this study, in 86 older people (mean age = 64.42, SD = 3.93), we investigated the relationship between the CAR and WS, a commonly used measure of physical performance in the older population that has also been related to health problems, such as cardiovascular disease and executive function performance in older people. Additionally, we studied whether the relationship between the CAR and WS was independent from cortisol levels on awakening and several possible confounders. Results showed that a CAR of reduced magnitude (measured with 3 samples each day, for two consecutive days, and calculated as the area under the curve with respect to the increase), but not cortisol levels on awakening, was related to slower WS. In addition, this relationship was independent from cortisol levels on awakening. It is possible that a CAR of reduced magnitude would contribute to less diurnal cortisol variability, affecting physical performance. Additionally, it is possible that a CAR of reduced magnitude affects WS through a possible negative effect on executive function, or that the association between the CAR and WS is due to the fact that both are related to similar health problems and to changes in cognitive performance in older people. PMID- 27191843 TI - The EARP Complex and Its Interactor EIPR-1 Are Required for Cargo Sorting to Dense-Core Vesicles. AB - The dense-core vesicle is a secretory organelle that mediates the regulated release of peptide hormones, growth factors, and biogenic amines. Dense-core vesicles originate from the trans-Golgi of neurons and neuroendocrine cells, but it is unclear how this specialized organelle is formed and acquires its specific cargos. To identify proteins that act in dense-core vesicle biogenesis, we performed a forward genetic screen in Caenorhabditis elegans for mutants defective in dense-core vesicle function. We previously reported the identification of two conserved proteins that interact with the small GTPase RAB 2 to control normal dense-core vesicle cargo-sorting. Here we identify several additional conserved factors important for dense-core vesicle cargo sorting: the WD40 domain protein EIPR-1 and the endosome-associated recycling protein (EARP) complex. By assaying behavior and the trafficking of dense-core vesicle cargos, we show that mutants that lack EIPR-1 or EARP have defects in dense-core vesicle cargo-sorting similar to those of mutants in the RAB-2 pathway. Genetic epistasis data indicate that RAB-2, EIPR-1 and EARP function in a common pathway. In addition, using a proteomic approach in rat insulinoma cells, we show that EIPR-1 physically interacts with the EARP complex. Our data suggest that EIPR-1 is a new interactor of the EARP complex and that dense-core vesicle cargo sorting depends on the EARP-dependent trafficking of cargo through an endosomal sorting compartment. PMID- 27191846 TI - Quantitative, Qualitative and Geospatial Methods to Characterize HIV Risk Environments. AB - Increasingly, 'place', including physical and geographical characteristics as well as social meanings, is recognized as an important factor driving individual and community health risks. This is especially true among marginalized populations in low and middle income countries (LMIC), whose environments may also be more difficult to study using traditional methods. In the NIH-funded longitudinal study Mapa de Salud, we employed a novel approach to exploring the risk environment of female sex workers (FSWs) in two Mexico/U.S. border cities, Tijuana and Ciudad Juarez. In this paper we describe the development, implementation, and feasibility of a mix of quantitative and qualitative tools used to capture the HIV risk environments of FSWs in an LMIC setting. The methods were: 1) Participatory mapping; 2) Quantitative interviews; 3) Sex work venue field observation; 4) Time-location-activity diaries; 5) In-depth interviews about daily activity spaces. We found that the mixed-methodology outlined was both feasible to implement and acceptable to participants. These methods can generate geospatial data to assess the role of the environment on drug and sexual risk behaviors among high risk populations. Additionally, the adaptation of existing methods for marginalized populations in resource constrained contexts provides new opportunities for informing public health interventions. PMID- 27191848 TI - Recent Clinical Trials in Osteoporosis: A Firm Foundation or Falling Short? AB - The global burden of osteoporotic fractures is associated with significant morbidity, mortality, and healthcare costs. We examined the ClinicalTrials.gov database to determine whether recently registered clinical trials addressed prevention and treatment in those at high risk for fracture. A dataset of 96,346 trials registered in ClinicalTrials.gov was downloaded on September 27, 2010. At the time of the dataset download, 40,970 interventional trials had been registered since October 1, 2007. The osteoporosis subset comprised 239 interventional trials (0.6%). Those trials evaluating orthopedic procedures were excluded. The primary purpose was treatment in 67.0%, prevention in 20.1%, supportive care in 5.8%, diagnostic in 2.2%, basic science in 3.1%, health services research in 0.9%, and screening in 0.9%. The majority of studies (61.1%) included drug-related interventions. Most trials (56.9%) enrolled only women, 38.9% of trials were open to both men and women, and 4.2% enrolled only men. Roughly one fifth (19.7%) of trials excluded research participants older than 65 years, and 33.5% of trials excluded those older than 75 years. The funding sources were industry in 51.0%, the National Institutes of Health in 6.3%, and other in 42.7%. We found that most osteoporosis-related trials registered from October 2007 through September 2010 examined the efficacy and safety of drug treatment, and fewer trials examined prevention and non-drug interventions. Trials of interventions that are not required to be registered in ClinicalTrials.gov may be underrepresented. Few trials are specifically studying osteoporosis in men and older adults. Recently registered osteoporosis trials may not sufficiently address fracture prevention. PMID- 27191849 TI - Attraction Propagation: A User-Friendly Interactive Approach for Polyp Segmentation in Colonoscopy Images. AB - The article raised a user-friendly interactive approach-Attraction Propagation (AP) in segmentation of colorectal polyps. Compared with other interactive approaches, the AP relied on only one foreground seed to get different shapes of polyps, and it can be compatible with pre-processing stage of Computer-Aided Diagnosis (CAD) under the systematically procedure of Optical Colonoscopy (OC). The experimental design was based on challenging distinct datasets that totally includes 1691 OC images, and the results demonstrated that no matter in accuracy or calculating speed, the AP performed better than the state-of-the-art. PMID- 27191850 TI - Identifying Neurocognitive Decline at 36 Months among HIV-Positive Participants in the CHARTER Cohort Using Group-Based Trajectory Analysis. AB - INTRODUCTION: While HIV-associated neurocognitive impairment remains common despite the widespread use of combined antiretroviral therapy (cART), there have been relatively few studies investigating the trajectories of neurocognitive change in longitudinal NeuroAIDS studies. OBJECTIVE: To estimate the magnitude and pattern of neurocognitive change over the first 3 years of follow-up using Group-Based Trajectory Analysis (GBTA) applied to participants in the longitudinal arm of the CHARTER cohort. METHOD: The study population consisted of 701 CHARTER participants who underwent neuropsychological (NP) testing on at least 2 occasions. Raw test scores on 15 NP measures were modeled using GBTA. Each trajectory was categorized as stable, improved or declined, according to two different criteria for change (whether the magnitude of the estimated change at 36 months differed >= 0.5 standard deviations from baseline value or changed by > the standard error of measurement estimated at times 1 and 2). Individuals who declined on one or more NP measures were categorized as decliners. RESULTS: Overall, 111 individuals (15.8%) declined on at least one NP test over 36 months, with the vast majority showing decline on a single NP test (93/111-83.8%). The posterior probability of group assignment was high in most participants (71%) after only 2 sessions, and in the overwhelming majority of those with 3+ sessions. Heterogeneity of trajectories was the norm rather than the exception. Individuals who declined had, on average, worse baseline NP performance on every test, were older, had a longer duration of HIV infection and more follow-up sessions. CONCLUSION: The present study identified heterogeneous trajectories over 3 years across 15 NP raw test scores using GBTA. Cognitive decline was observed in only a small subset of this study cohort. Decliners had demographics and HIV characteristics that have been previously associated with cognitive decline, suggesting clinical validity for the method. PMID- 27191851 TI - Treatment of Thyroid Dysfunctions Decreases the Risk of Cerebrovascular Events in Men but Not in Women: Results of the MONICA/KORA Cohort Study. AB - OBJECTIVE: Thyroid disorders are well known to be associated with cardiovascular diseases. Some studies have shown that the negative effects of thyroid disorders are partially reversible after adequate treatment. The aim of this analysis was to assess the risk of incident ischemic cerebrovascular diseases in study participants treated for thyroid dysfunctions in a population-based cohort study. METHODS: For the presented analyses data from 8564 male and 8714 female individuals aged 25 to 74 years of the MONICA/KORA cohort were used (median follow-up 14.0 years). A combined binary variable "thyroid disorder" (TDC) was created utilizing data on self-reported physician-treated thyroid disorders and information about medication use. To examine the association between TDC and incident ischemic cerebrovascular events, we performed multiple adjusted Cox proportional hazard regression models and calculated hazard ratios and corresponding 95% confidence intervals (HR, 95%CI). RESULTS: During follow-up between 1984 and 2008/2009, 514 incident fatal and non-fatal ischemic cerebrovascular events occurred in men and 323 in women. At baseline, 3.5% of men and 15.6% of women reported TDC. In the fully adjusted model, males who reported TDC had a significantly reduced risk of ischemic cerebrovascular events (HR = 0.52, 95%CI = 0.29-0.92). A similar result was obtained in men, when we utilized information on thyroid hormones use only. For the total study population and for women with TDC we found no association with ischemic cerebrovascular events. CONCLUSIONS: In our longitudinal analyses subjects with treated thyroid diseases had no increased risk of incident ischemic cerebrovascular events. Surprisingly in males, even a significantly reduced risk of incident ischemic cerebrovascular events was found, a result that deserves further clarification. PMID- 27191854 TI - Fibrin clot formation and fibrinolysis in patients with a history of coronary stent thrombosis. AB - INTRODUCTION: Coronary stent thrombosis is a devastating complication of percutaneous coronary intervention (PCI). Multiple factors underlie the pathophysiological mechanisms of stent thrombosis. Previous studies demonstrated that patients with stent thrombosis, compared to control PCI patients, formed denser fibrin clots in vitro which were more resistant to fibrinolysis, suggesting that altered fibrin clot properties may contribute to the pathophysiology of stent thrombosis. We assessed the plasma fibrin clot formation and fibrinolysis of patients with and without stent thrombosis. METHODS: Cases (patients with stent thrombosis) and matched controls (patients without stent thrombosis) were included for a matched case-control study. Matching was performed on indication and time of the index PCI (initial stent implantation) from the cases. Fibrin clot formation and fibrinolysis were assessed in vitro by turbidimetric assays, with human thrombin to initiate fibrin polymerization and tissue type plasminogen activator to initiate fibrinolysis. Lag time, maximal absorbance and clot lysis time were determined by these assays. RESULTS: In total, 27 cases and 27 controls were included. No significant differences were observed between cases and controls in lag time (173 vs. 162s, p=0.18), maximal absorbance (0.78 vs. 0.83, p=0.36), and clot lysis time (69 vs. 71min, p=0.78). Fibrin clot formation and fibrinolysis were not associated with stent thrombosis. CONCLUSIONS: Plasma fibrin clot formation and fibrinolysis were not significantly different between patients with stent thrombosis and matched control patients, suggesting that fibrin clot formation and fibrinolysis play no significant role in the pathophysiology of stent thrombosis. PMID- 27191852 TI - Cystathione gamma lyase/Hydrogen Sulphide Pathway Up Regulation Enhances the Responsiveness of alpha1A and alpha1B-Adrenoreceptors in the Kidney of Rats with Left Ventricular Hypertrophy. AB - The purpose of the present study was to investigate the interaction between H2S and NO (nitric oxide) in the kidney and to evaluate its impact on the functional contribution of alpha1A and alpha1B-adrenoreceptors subtypes mediating the renal vasoconstriction in the kidney of rats with left ventricular hypertrophy (LVH). In rats the LVH induction was by isoprenaline administration and caffeine in the drinking water together with intraperitoneal administration of H2S. The responsiveness of alpha1A and alpha1B to exogenous noradrenaline, phenylephrine and methoxaminein the absence and presence of 5-methylurapidil (5-MeU) and chloroethylclonidine (CEC) was studied. Cystathione gamma lyase (CSE), cystathione beta synthase (CBS), 3-mercaptopyruvate sulphar transferase (3-MST) and endothelial nitric oxide synthase (eNOS) were quantified. There was significant up regulation of CSE and eNOS in the LVH-H2S compared to the LVH group (P<0.05). Baseline renal cortical blood perfusion (RCBP) was increased (P<0.05) in the LVH-H2S compared to the LVH group. The responsiveness of alpha1A adrenergic receptors to adrenergic agonists was increased (P<0.05) after administration of low dose 5-Methylurapidil in the LVH-H2S group while alpha1B adrenergic receptors responsiveness to adrenergic agonists were increased (P<0.05) by both low and high dose chloroethylclonidine in the LVH-H2S group. Treatment of LVH with H2S resulted in up-regulation of CSE/H2S, CBS, and 3-MST and eNOS/NO/cGMP pathways in the kidney. These up regulation of CSE/H2S, CBS, and 3-MST and eNOS/NO/cGMP pathways enhanced the responsiveness of alpha1A and alpha1B-adrenoreceptors subtypes to adrenergic agonists in LVH-H2S. These findings indicate an important role for H2S in modulating deranged signalling in the renal vasculature resulting from LVH development. PMID- 27191855 TI - Non-neural androgen receptor promotes androphilic odor preference in mice. AB - In mice, male-typical preference for female olfactory cues results largely from sexually differentiated testosterone production. It is currently unclear on which cells and tissues testosterone acts to produce male-typical preference for female olfactory cues. To further address the site of androgen action on olfactory preference, we have developed a loxP-based transgenic mouse that overexpresses androgen receptors (AR) only when activated by Cre. We used this transgene to overexpress AR globally in all tissues using a CMV-Cre driver and a Nestin-Cre driver to overexpress AR selectively in neural tissue. We then examined olfactory preference in transgenic and wildtype (Wt) littermates by simultaneously exposing animals to female-soiled, male-soiled and clean bedding. Ubiquitous overexpression of AR in CMV-AR mice increased preference for male bedding, whereas neural-specific AR overexpression in Nestin-AR transgenic mice did not differ from wildtype siblings in olfactory preference. Neural activation of olfactory brain areas in response to female-soiled bedding was also evaluated in these mice by measuring FOS immunoreactivity. This revealed a decrease in neural activity along the accessory olfactory pathway that accompanied the decrease in preference for female odors in CMV-AR males, compared to both Nestin-AR and Wt male siblings. Together, results indicate that androgens act via non-neural AR to mediate olfactory preference and neural responses to olfactory stimuli, and further suggest that AR in non-neural tissues can promote androphilic odor preferences in male mice.In mice, male-typical preference for female olfactory cues results largely from sexually differentiated testosterone production. It is currently unclear on which cells and tissues testosterone acts to produce male typical preference for female olfactory cues. To further address the site of androgen action on olfactory preference, we have developed a loxP-based transgenic mouse that overexpresses androgen receptors (AR) only when activated by Cre. We used this transgene to overexpress AR globally in all tissues using a CMV-Cre driver and a Nestin-Cre driver to overexpress AR selectively in neural tissue. We then examined olfactory preference in transgenic and wildtype (Wt) littermates by simultaneously exposing animals to female-soiled, male-soiled and clean bedding. Ubiquitous overexpression of AR in CMV-AR mice increased preference for male bedding, whereas neural-specific AR overexpression in Nestin AR transgenic mice did not differ from wildtype siblings in olfactory preference. Neural activation of olfactory brain areas in response to female-soiled bedding was also evaluated in these mice by measuring FOS immunoreactivity. This revealed a decrease in neural activity along the accessory olfactory pathway that accompanied the decrease in preference for female odors in CMV-AR males, compared to both Nestin-AR and Wt male siblings. Together, results indicate that androgens act via non-neural AR to mediate olfactory preference and neural responses to olfactory stimuli, and further suggest that AR in non-neural tissues can promote androphilic odor preferences in male mice. PMID- 27191853 TI - Perinatal Exposure to a Diet High in Saturated Fat, Refined Sugar and Cholesterol Affects Behaviour, Growth, and Feed Intake in Weaned Piglets. AB - The increased consumption of diets high in saturated fats and refined sugars is a major public health concern in Western human societies. Recent studies suggest that perinatal exposure to dietary fat and/or sugar may affect behavioural development. We thus investigated the effects of perinatal exposure to a high-fat high-sugar diet (HFS) on behavioural development and production performance of piglets. Thirty-two non-obese sows and their piglets were allocated to 1 of 4 treatments in a 2 * 2 factorial design, with 8-week prenatal (gestation) and 8 week postnatal (lactation and post-weaning) exposure to a HFS diet (12% saturated fat, 18.5% sucrose, 1% cholesterol) or control low-fat low-sugar high-starch diets as factors. From weaning onwards (4 weeks of age), piglets were housed in group of 3 littermates (n = 8 groups/treatment) and fed ad libitum. After the end of the dietary intervention (8 weeks of age), all the piglets were fed a standard commercial diet. Piglet behaviours in the home pens were scored, and skin lesions, growth, feed intake and feed efficiency were measured up to 8 weeks after the end of the dietary treatment, i.e. until 16 weeks of age. At the end of the dietary treatment (8 weeks of age), response to novelty was assessed in a combined open field and novel object test (OFT/NOT). During the weeks following weaning, piglets fed the postnatal HFS diet tended to be less aggressive (p = 0.06), but exhibited more oral manipulation of pen mates (p = 0.05) than controls. Compared to controls, piglets fed the prenatal or postnatal HFS diet walked more in the home pen (p <= 0.05), and tended to have fewer skin lesions (p < 0.10). Several behavioural effects of the postnatal HFS diet depended on the prenatal diet, with piglets subjected to a switch of diet at birth being more active, and exploring feeding materials, pen mates, and the environment more than piglets that remained on the same diet. Behaviours during the OFT/NOT were not affected by the diet. The intake of the postnatal HFS diet drastically reduced feed intake, but improved feed efficiency up to 8 weeks after the end of the dietary intervention, i.e. 16 weeks of age (p < 0.0001 for both). Our study highlights the key role of prenatal and postnatal nutritional interactions for early behavioural development, and reveals programming effects of early life nutrition on voluntary feed intake of piglets later in life. PMID- 27191856 TI - The strain of an accompanying conspecific affects the efficacy of social buffering in male rats. AB - Social buffering is a phenomenon in which stress in an animal is ameliorated when the subject is accompanied by a conspecific animal(s) during exposure to distressing stimuli. We previously reported that in male Wistar rats, the presence of another Wistar rat mitigates conditioned fear responses to an auditory conditioned stimulus (CS). Subsequent analyses revealed several characteristics of this social buffering of conditioned fear responses. However, information regarding the specificity of accompanying conspecifics is still limited. In the present study, we assessed whether rats of other strains could induce social buffering in Wistar rats. When a fear-conditioned Wistar subject was re-exposed to the CS alone, we observed increased freezing and decreased investigation and walking, as well as elevated corticosterone levels. The presence of a Wistar, Sprague-Dawley, or Long-Evans rat blocked these responses, suggesting that social buffering was induced by these strains of rats. In contrast, a Fischer 344 rat did not induce social buffering in the Wistar subject. We further found that an inbred Lewis rat induced social buffering whereas a Brown Norway rat, a strain that has been established independently from Wistar rats, did not. These results suggest that the difference in origin, rather than the inbred or outbred status of the associate rat, seemed to account for the lack of social buffering induced by the F344 rats. Based on these findings, we conclude that strains of an accompanying conspecific can affect the efficacy of social buffering in rats. PMID- 27191858 TI - Palladium-Catalyzed Regioselective Difluoroalkylation and Carbonylation of Alkynes. AB - A novel, four-component synthetic strategy to synthesize a series of beta difluoroalkyl unsaturated esters/amides with high regioslectivity is described. This Pd-catalyzed difluoroalkylation and carbonylation reaction can be carried out with simple starting materials. Through this protocol, two new C-C bonds (including one C-CF2 bond) and one C-O(N) bond are constructed simultaneously in a single step. The synthetic utility of this reaction system has been certified by the applicability to a wide scope of alkynes and nucleophiles. Preliminary mechanistic studies suggest that the difluoroalkyl radical pathway is involved in this reaction. PMID- 27191857 TI - Evaluating the Impact of Naltrexone on the Rat Gambling Task to Test Its Predictive Validity for Gambling Disorder. AB - Gambling Disorder has serious consequences and no medications are currently approved for the treatment of this disorder. One factor that may make medication development difficult is the lack of animal models of gambling that would allow for the pre-clinical screening of efficacy. Despite this, there is evidence from clinical trials that opiate antagonists, in particular naltrexone, may be useful in treating gambling disorder. To-date, the effects of naltrexone on pre-clinical models of gambling have not been evaluated. The purpose of the present study was to evaluate the effects of naltrexone in an animal model of gambling, the rat gambling task (rGT), to determine whether this model has some predictive validity. The rGT is a model in which rats are given a choice of making either a response that produces a large reward or a small reward. The larger the reward, the greater the punishment, and thus this task requires that the animal inhibit the 'tempting' choice, as the smaller reward option produces overall the most number of rewards per session. People with gambling disorder chose the tempting option more, thus the rGT may provide a model of problem gambling. It was found that naltrexone improved performance on this task in a subset of animals that chose the 'tempting', disadvantageous choice, more at baseline. Thus, the results of this study suggest that the rGT should be further investigated as a pre clinical model of gambling disorder and that further investigation into whether opioid antagonists are effective in treating Gambling Disorder may be warranted. PMID- 27191859 TI - Association between Concentrations of Metals in Urine and Adult Asthma: A Case Control Study in Wuhan, China. AB - BACKGROUND: Several metals have been reported to be associated with childhood asthma. However, the results on relationships between metals and risk of childhood asthma are inconclusive, and the research on adult asthma in the Chinese general population is rare. OBJECTIVES: To investigate potential associations between levels of urinary metals and adult asthma. METHODS: A case control study of 551 adult asthma cases and 551 gender- and age-matched controls was conducted in Wuhan, China. Demographic information was obtained, and lung function was assessed. The urinary concentrations of 22 metals were measured by inductively coupled plasma mass spectrometry. RESULTS: After adjusting for other metalsand other covariates, urinary cadmium, molybdenum, chromium, copper, uranium and selenium were positively associated with asthma, with odds ratios (95% CI) of 1.69 (1.00, 2.85), 3.76 (2.30, 6.16), 4.89 (3.04, 7.89), 6.06 (3.27, 11.21), 6.99 (4.37, 11.19) and 9.17 (4.16, 20.21), respectively. By contrast, urinary lead, barium, iron, zinc, nickel, manganese and rubidium were negatively associated with asthma, with odds ratios (95% CI) of 0.48 (0.29, 0.80), 0.44 (0.27, 0.71), 0.41 (0.26, 0.64), 0.40 (0.24, 0.66), 0.30 (0.22, 0.41), 0.23 (0.14, 0.39) and 0.07 (0.03, 0.15), respectively. When comparing urinary metals in different subgroups of cases with those in matched controls, the associations of above 13 metals with asthma prevalence were nearly the same. CONCLUSIONS: Our results suggested that asthma prevalence in the Chinese adults was positively associated with urinary chromium, chromium, selenium, molybdenum, cadmium, and uranium, and negatively associated with urinary manganese, iron, nickel, zinc, rubidium, barium and lead. Additional research with larger populations in different regions is required to support our findings. PMID- 27191861 TI - Safety and Outcome of Microincision Vitreous Surgery in Uveitis. AB - PURPOSE: To report the outcome of microincision vitreous surgery (MIVS) in uveitis. METHODS: In total, 103 patients (106 eyes) underwent diagnostic MIVS between March 2012 and April 2015. Postoperative evaluation included vitreous haze grading from clinical/electronic records, best-corrected visual acuity (BCVA), and complications. RESULTS: Mean age was 36.8 +/- 13.9 years (range: 8-80 years). Mean follow-up after MIVS was 12.2 +/- 7.2 months (median 12 months). Mean vitreous haze grading was 2.39 +/- 0.98 (preoperatively), 0.36 +/- 0.73 postoperatively (1 week), and 0.02 +/- 0.2 at 1 month (p < 0.001). Mean BCVA was 1.5 +/- 1.0 logMAR preoperatively and 0.72 +/- 0.68 logMAR at 1 month (p = 0.000). Postoperative complications included cataract (14.6%), rise in intraocular pressure (13.2%), vitreous hemorrhage (4.7%), hypotony (3.2%), retinal detachment (2.8%), epiretinal membrane (2.8%), and worsening of inflammation (0.9%). CONCLUSIONS: MIVS is safe and may have a therapeutic role in uveitis. PMID- 27191863 TI - Do Surgeons or Hospital Economics Ultimately Decide Operative Approach? PMID- 27191860 TI - Clinical evaluation of 4D PET motion compensation strategies for treatment verification in ion beam therapy. AB - A clinical trial named PROMETHEUS is currently ongoing for inoperable hepatocellular carcinoma (HCC) at the Heidelberg Ion Beam Therapy Center (HIT, Germany). In this framework, 4D PET-CT datasets are acquired shortly after the therapeutic treatment to compare the irradiation induced PET image with a Monte Carlo PET prediction resulting from the simulation of treatment delivery. The extremely low count statistics of this measured PET image represents a major limitation of this technique, especially in presence of target motion. The purpose of the study is to investigate two different 4D PET motion compensation strategies towards the recovery of the whole count statistics for improved image quality of the 4D PET-CT datasets for PET-based treatment verification. The well known 4D-MLEM reconstruction algorithm, embedding the motion compensation in the reconstruction process of 4D PET sinograms, was compared to a recently proposed pre-reconstruction motion compensation strategy, which operates in sinogram domain by applying the motion compensation to the 4D PET sinograms. With reference to phantom and patient datasets, advantages and drawbacks of the two 4D PET motion compensation strategies were identified. The 4D-MLEM algorithm was strongly affected by inverse inconsistency of the motion model but demonstrated the capability to mitigate the noise-break-up effects. Conversely, the pre reconstruction warping showed less sensitivity to inverse inconsistency but also more noise in the reconstructed images. The comparison was performed by relying on quantification of PET activity and ion range difference, typically yielding similar results. The study demonstrated that treatment verification of moving targets could be accomplished by relying on the whole count statistics image quality, as obtained from the application of 4D PET motion compensation strategies. In particular, the pre-reconstruction warping was shown to represent a promising choice when combined with intra-reconstruction smoothing. PMID- 27191864 TI - The impact of food structure on taste and digestibility. AB - The modern food chain depends on complex interactions between businesses from farming to retail. Until recently their success depended upon providing consumers with safe, convenient food which was pleasant to eat, at a reasonable value for money. This has required detailed research into how food structures deliver recognisable and preferred types of foods, from hard solids to thick liquids. Fortunately the consumer is able to detect and report sensations of texture and flavour which can be related to the composition, structure and breakdown of food in the mouth. Chemists, physicists and engineers can attempt to build mechanistic models of how structures relate to perception. The state of the art in our understanding and design capabilities are reviewed. In the developed world, the success is self evident as food prices (as a proportion of income) have decreased and there is a surfeit of choice on the supermarket shelf. More recently, the requirement to add a balanced healthy diet to the simple pleasure of eating has become the new target. This is a different type of challenge. The effects of diet on health are long term, and not easily reported by the consumer. Whilst we know something of how the digestive tract works in breaking down foods, we know little of how food structure impacts upon this process, and even less of how the neural and metabolic feedback systems operate to relate food structures to satiety and satiation. Therefore, in the absence of causal models relating structures to eating habits, structures designed to achieve both immediate pleasure and long term healthy eating are much more speculative. What we think we know, and what we need to know are reviewed. There is no doubt that other skills, in nutrition, physiology, neuroscience, and molecular biology etc. will need to be added to the classical approaches of food materials science and engineering if these challenges are to be met. PMID- 27191862 TI - Substance Abuse Among Blacks Across the Diaspora. AB - BACKGROUND: Lower rates of substance abuse are found among Black Americans compared to Whites, but little is known about differences in substance abuse across ethnic groups within the black population. OBJECTIVES: We examined prevalence rates of substance abuse among Blacks across three geographic regions (US, Jamaica, Guyana). The study also sought to ascertain whether length of time, national context and major depressive episodes (MDE) were associated with substance abuse. METHODS: We utilized three different data sources based upon probability samples collected in three different countries. The samples included 3,570 African Americans and 1,621 US Caribbean Black adults from the 2001-2003 National Survey of American Life (NSAL). An additional 1,142 Guyanese Blacks and 1,176 Jamaican Blacks living in the Caribbean region were included from the 2005 NSAL replication extension study, Family Connections Across Generations and Nations (FCGN). Mental disorders were based upon DSM-IV criteria. For the analysis, we used descriptive statistics, chi-square, and multivariate logistic regression analytic procedures. RESULTS: Prevalence of substance abuse varied by national context, with higher rates among Blacks within the United States compared to the Caribbean region. Rates of substance abuse were lower overall for women, but differ across cohorts by nativity and length of time in the United States, and in association with major depressive episode. CONCLUSIONS: The study highlights the need for further examination of how substance abuse disparities between US-based and Caribbean-based populations may become manifested. PMID- 27191865 TI - A Novel Capsulorhexis Technique in White Cataract Surgery. PMID- 27191866 TI - Identifying 2'-O-methylationation sites by integrating nucleotide chemical properties and nucleotide compositions. AB - 2'-O-methylationation is an important post-transcriptional modification and plays important roles in many biological processes. Although experimental technologies have been proposed to detect 2'-O-methylationation sites, they are cost ineffective. As complements to experimental techniques, computational methods will facilitate the identification of 2'-O-methylationation sites. In the present study, we proposed a support vector machine-based method to identify 2'-O methylationation sites. In this method, RNA sequences were formulated by nucleotide chemical properties and nucleotide compositions. In the jackknife cross-validation test, the proposed method obtained an accuracy of 95.58% for identifying 2'-O-methylationation sites in the human genome. Moreover, the model was also validated by identifying 2'-O-methylation sites in the Mus musculus and Saccharomyces cerevisiae genomes, and the obtained accuracies are also satisfactory. These results indicate that the proposed method will become a useful tool for the research on 2'-O-methylation. PMID- 27191867 TI - Elevated Pertussis Reporting in Response to 2011-2012 Outbreak, New York City, New York, USA. PMID- 27191868 TI - Editorial. PMID- 27191869 TI - The importance of scientific production for the political consolidation of professional practice. PMID- 27191870 TI - Otoacoustic emissions in newborns with mild and moderate perinatal hypoxia. AB - Introduction Severe neonatal hypoxia (as evidenced by the Apgar value) is currently considered the only risk for hearing loss. Hypoxia is one of the most common causes of injury and cell death. The deprivation of oxygen in mild or moderate cases of hypoxia, although smaller, occurs and could cause damage to the auditory system. Objective To investigate the amplitude of otoacoustic emissions in neonates at term with mild to moderate hypoxia and no risk for hearing loss. Methods We evaluated 37 newborns, divided into two groups: a control group of 25 newborns without hypoxia and a study group of 12 newborns with mild to moderate hypoxia. TEOAE and DPOAE were investigated in both groups. Results The differences between groups were statistically significant in the amplitude of DPOAE at the frequencies of 1000, 2800, 4000 and 6000 Hz. In TEOAE, statistically significant differences were found in all tested frequency bands. OAE of the study group were lower than those in the control group. Conclusion Although the occurrence of mild and moderate neonatal hypoxia is not considered a risk factor for hearing loss, deprivation of minimum oxygen during neonatal hypoxia seems to interfere in the functioning of the outer hair cells and, consequently, alter the response level of otoacoustic emissions. Thus, hese children need longitudinal follow-up in order to identify the possible impact of these results on language acquisition and future academic performance. PMID- 27191871 TI - Evaluation of the hearing protector in a real work situation using the field microphone-in-real-ear method. AB - Purpose To evaluate the effectiveness of the attenuation of a hearing protector (HP) in a real work situation using the field-microphone-in-real-ear method (f MIRE). Methods Eighteen individuals of both genders (mean age of 47.17+/-8 years) participated in this study. In the workplace, the personal attenuation level of the HP was assessed using the f-MIRE method, followed by orientation about the importance of using the HP, cleaning and storing the device, and training for effective placement. Results The analyses showed a significant statistic attenuation for all of the collected data (total noise, by frequency band and dose) when the noise levels in the lapel microphone and the probe microphone were compared. In the comparison of the attenuation values provided by the manufacturer and those found in this study, we observed higher values for the manufacturer in all frequency bands. No difference was observed for the noise levels in the different activities and times evaluated. Conclusion The findings of this study enabled us to know the personal level of attenuation of the HP during a real work situation, which was within the limits of tolerance. It was also possible to collect information about the environmental noise to which these workers are exposed. We noticed situations where this level exceeded the safety values, and therefore it is recommended the use of the HP. It is important that more studies are conducted using the f-MIRE method, because it may be an ally to assess the effectiveness of the HP attenuation in the workplace. PMID- 27191872 TI - Quality of life in adult cochlear implant users. AB - Objective To evaluate the quality of life (QOL) of adult cochlear implant users (CI) and compare it with the QOL of adults with normal hearing; and study the influence of the variables socioeconomic status, education, age at assessment, auditory sensory deprivation time, device usage time and performance in auditory speech perception tests in the QOL of adult cochlear implant users. Design The QOL was assessed using the World Health Organization Quality of Life (WHOQOL BREF) generic assessment questionnaire. Study sample Seventy adult CI users formed the experimental group (EG) and 50 adults with normal hearing formed the control group (CG). Results The EG scores were close to the maximum score in satisfactory quality of life for all domains of the WHOQOL-BREF and there were similar results between the EG and CG. The variables age at assessment, duration of auditory sensory deprivation, duration of CI use and performance in auditory speech perception did not influence the results of the QOL of adult cochlear implant users. Conclusion Evaluating the QOL should be a concern of interdisciplinary teams in CI for an intervention with humanized care. PMID- 27191873 TI - The effectiveness of the head-turn-plus-chin-down maneuver for eliminating vallecular residue. AB - Purpose When swallowing efficiency is impaired, residue accumulates in the pharynx. Cued or spontaneous swallows in the head neutral position do not always successfully clear residue. We investigated the impact of a novel maneuver on residue clearance by combining a head turn with the chin down posture. Methods Data were collected from 26 participants who demonstrated persistent vallecular residue after an initial head neutral clearance swallow in videofluoroscopy. Participants were cued to perform a head-turn-plus-chin-down swallow, with the direction of head turn randomized. Pixel-based measures of residue in the vallecular space before and after the maneuver were made on still frame lateral images using ImageJ software. Measures of % full and the Normalized Residue Ratio Scale (NRRS) were extracted. Univariate analyses of variance were used to detect significant reductions in residue. Results On average, pre-maneuver measures showed residue filling 56-73% of the valleculae, depending on stimulus consistency (NRRS scores: 0.2-0.4). More than 80% of pre-swallow measures displayed NRRS ratios > 0.06, a threshold previously linked to increased risk of post-swallow aspiration. Conclusion The head-turn-plus-chin-down maneuver achieved significant reductions in residue for thin and nectar-thick fluids, suggesting that this maneuver can be effective in reducing persistent vallecular residue with these consistencies. PMID- 27191874 TI - Linguistic performance in 2 years old preterm, considering chronological age and corrected age. AB - Introduction Preterm birth causes problems that are not restricted to perinatal mortality. Some premature, even in the absence of brain damage, have negative effects on various aspects of development, such as language difficulties. Objective This study aimed to verify the linguistic performance of preterm children at 2 years old, considering the chronological age and corrected age. Methods The study included 23 preterm children and applied the Test of Early Language Development- TELD-3 to assess the language skills. Results The premature children showed the linguistic performance alterations in Teld-3 in 39.13% of cases. They were also analyzed considering the delay to the chronological and corrected ages and there was no difference in performance for both receptive subtests (p = 0.250) and significant (p = 1.000). Conclusion The group of premature children at 2 years is a population at risk for language disorders that cannot be compensated with age correction. PMID- 27191876 TI - International Classification of Functioning, Disability and Health, and aphasia: a study of social participation. AB - Purpose To identify and analyze the impact of aphasia on social participation and daily activities of people affected by this disease, as well as to understand implications of environmental factors on limitations and restrictions of participation according to the criteria established by the International Classification of Functioning, Disability and Health. Method Data presented and discussed were collected from 12 people of both sexes with aphasia participating in an Interdisciplinary Group for Coexistence. Data were collected between October 2011 and March 2013 and analyzed based on the International Classification of Functioning, Disability and Health checklist. Results All subjects had restrictions on performing and participating in their daily activities, either by biological, environmental or socio-cultural factors. Conclusions The restriction in participation was the most evident, mostly due to environmental factors than sequels resulting from the brain injury. PMID- 27191875 TI - Spelling performance of students with developmental dyslexia and with developmental dyslexia associated to attention deficit disorder and hyperactivity. AB - Purpose to analyze and classify the spelling performance according to the semiology of spelling error of children with developmental dyslexia (DD) and with developmental dyslexia associated to attention deficit disorder and hyperactivity(DD and ADHD) comparing them to a group of children without learning process complaints. Methods Seventy students, from the third to fifth grade, participated in this study divided as follows: 32 children without complaints of learning difficulties (GI), mean age 9.5 years; 22 students with developmental dyslexia (GII), mean age 10 years; 16 scholars with developmental dyslexia associated to attention deficit disorders and hyperactivity (GIII), mean age 9.9. Spelling skills were assessed through a standardized word dictation task. Results Data indicated that GII and GIII children presented lower performance when compared with typically developed children. There was no statistical difference between the performance of GII and GIII children regarding the score reached in spelling, although GIII children presented the lowest performance. We observed differences between GII and GIII only in the type of misspelling. Conclusion Data from this research contribute to develop better programs for intervention in the studied population. PMID- 27191877 TI - The influence of listener training on the perceptual assessment of hypernasality. AB - Introduction A high agreement in the perceptual assessment of hypernasality among different listeners is difficult to achieve. Prior listener training and the standardization of analysis criteria may be effective strategies to decrease the effect of perceptual assessment subjectivity and increase the agreement among listeners. Objective To investigate the influence of prior training on agreement among different listeners in the perceptual assessment of hypernasality. Methods Three experienced speech-language pathologists analyzed 77 audio-recorded speech samples of individuals with repaired cleft palate. During the first phase, the listeners classified hypernasality according to their own criteria, using a 4 point scale. Seventy days later, they were required to complete the training to define the stimuli to be used as anchors for the assessment in the following phase. During the second phase, the listeners analyzed the same samples and rated hypernasality in a 4-point scale, using the anchors defined during training as the criteria. Intra- and interrater agreement in both the phases were calculated by the kappa coefficient. These values were statistically compared using the Z test. Results The intrarater agreement obtained between the two phases of the study ranged from 0.38 to 0.92, with a statistically significant difference for one of the listeners (p=0.004). The agreement for the hypernasality degree obtained among the three listeners after training (0.54) was significantly higher than that obtained before training (0.37; p=0.044). Conclusion Listener training and the definition of criteria to rate hypernasality lead to the increase of intra- and interrater agreement. PMID- 27191878 TI - Validity and reliability of the quality of masticatory function questionnaire applied in Brazilian adolescents. AB - Purpose proper chewing and swallowing functions have great importance in general health, since it potentially affects food's digestion and the subject's nutritional status. The aim was to assess the validity and reliability of the self-applied Quality of Masticatory Function Questionnaire (QMFQ) in a convenience (non-referred) sample of Brazilian adolescents divided into three groups: control (n=57), dental caries (n=51) and malocclusion (n=54). Methods caries and malocclusion were evaluated using DMF-S index (number of decayed, missing and filled primary and permanent surfaces) and Index of Orthodontic Treatment Need, respectively. The QMFQ comprises 26 items regarding frequency and intensity of chewing problems with five domains: Food-Mastication, Habits, Meat, Fruits and Vegetables. Data were submitted to descriptive statistics, Kolmogorov Smirnov and Chi-square tests. Psychometric evaluation included measures of reliability (internal consistency - Cronbach's alpha and matrix of correlation) and discriminant validity (Kruskal-Wallis/Dunn post-test). Results the instrument showed satisfactory internal consistency, with significant positive correlations between the domains scores except between Habits and Vegetables. Total scale Cronbach's alpha coefficient was 0.87 and the coefficient did not increase significantly with the removal of each domain. Significant differences were found between controls and caries group in Food-Mastication, Meat and Fruits scores. Caries group also showed higher median values in Food-Mastication and Fruits than the malocclusion group. Conclusion the Quality of Masticatory Function Questionnaire showed acceptable properties regarding internal consistency, reliability, and discriminant validity in evaluating the impact of caries on the perception of the masticatory function quality of Brazilian adolescents. PMID- 27191879 TI - Effect of time of contraction and rest on the masseter and anterior temporal muscles activity in subjects with temporomandibular disorder. AB - Purpose The main objective of this study was to investigate the effect of time of contraction and rest on the masseter and temporal muscles activity. Methods 49 female subjects between 18 and 30 years of age were divided into TMD (n: 26) and control groups (n: 23). Surface electromyograph was used to evaluate the anterior temporal and masseter muscles during contraction and rest protocols. The root means square, median frequency and slope coefficient of the linear regression line parameters were analyzed. Results A significant effect of time in the contraction and rest muscle protocols was found. TMD patients showed a significant decrease in median frequency in the right masseter muscle and the slope coefficient in the right temporal muscle during the contraction protocol to control subjects. Conclusion Despite the TMD patients presented with higher fatigue susceptibility compared to the control group, both groups must meet the maximum time of 5 s of maximum voluntary contraction and at least 30 s rest between successive contractions of masticatory muscles during clinical or research assessment protocols. PMID- 27191880 TI - Auditory-perceptual evaluation of rough and breathy voices: correspondence between analogical visual and numerical scale. AB - PURPOSE: To determine the cut-off values of different degrees of vocal roughness and breathiness in an analogical visual scale, from a numerical scale. METHODS: We selected 150 voices from both genders, with quality ranging from neutrality to intense deviations, and predominance of breathiness or roughness. The auditory perceptual assessment through two scales: 100-mm analogical visual scales and 4 point numerical scale. Intra and interrater reliability of auditory-perceptual ratings was analyzed using the Intraclass Correlation Coefficient. The cut-off values for graduation of roughness and breathiness voices were determinate using the analysis of the Receiver Operating Characteristic (ROC) curve, which is based on the sensitivity, specificity and efficiency. RESULTS: The intra and interrater reliability of auditory-perceptual ratings was excellent on both scales. The cut off values (mm) in the analogical visual scale, from the numeric scale, indicated a roughness distribution: 0-8.5 absence of the parameter; 8.5- 28.5 mild presence; 28.5- 59.5 moderate and 59.5- 100 intense. For breathiness, the distribution was: 0-8.5 absence of the parameter; 8.5-33.5 for mild presence; 33.5-52.5 moderate and 52.5-100 intense. CONCLUSION: The cut-off values found for the analogical visual scale conclude that the numerical scale zero, which represents the absence of parameter, corresponds to a small range of scores in the analogical visual scale. Furthermore, the third degree of the numerical scale corresponded to a wide range of the analogical visual scale. PMID- 27191881 TI - Teacher's voice: vocal tract discomfort symptoms, vocal intensity and noise in the classroom. AB - OBJECTIVE: To identify a possible correlation between teachers vocal intensity and the noise in the classroom, as well as between vocal intensity and the symptoms of vocal tract discomfort before and after classes. METHODS: 27 Elementary School I teachers participated in the study. We used the questionnaires "Vocal Production Condition of the Teacher" and "Vocal Tract Discomfort Scale - VTD" which were applied before and after the class. A properly calibrated noise meter was used for measuring noise in the classroom and the teachers' vocal intensity. RESULTS: There was a moderate positive correlation between vocal intensity and noise and also a significant difference between the VTD scale and the teachers with and without vocal complaint before and after classes. When compared separately on both occasions, there was an increase in the group's scores for both groups and with and without complaints. We found association of the vocal tract symptoms before and after classes, frequency of burning, itching, sore throat and sensitive throat were observed. The intensity of symptoms was significant for sore throat, itching and feeling of lump in the throat. We observed significant values of vocal intensity and frequency and intensity of symptoms for sensitive throat and lump in the throat before the class, and sore throat and lump in the throat after the. CONCLUSION: The increase in teacher's vocal intensity correlates to high noise levels in the classroom. The evidence suggests correlation between vocal intensity and discomfort of the vocal tract, with most of the symptoms reported in greater frequency and intensity after the class. PMID- 27191882 TI - Voice telerehabilitation in Parkinson's disease. AB - Parkinson's disease (PD) is a neurodegenerative condition associated with motor, neuropsychological, sensorial, and vocal symptoms. It has been suggested that eventual obstacles faced by many patients to reach speech therapy rehabilitation centers could be overcome with the use of synchronous telerehabilitation (real time) approach employing communication technologies. PURPOSE: To investigate the efficacy of vocal telerehabilitation in PD patients. METHODS: Twenty patients diagnosed with PD and with vocal complaints participated in this study. Patients were evaluated by videoconference (Adobe Connect 8) before and after treatment. Evaluation method consisted of perceptual analysis of vocal quality measured by the GRBASI scale. Treatment was conducted following the extended version of Lee Silverman method (LSVT-X). At the end of treatment all patients were requested to fill a questionnaire to assess their experience with telerehabilitation. RESULTS: Analysis revealed decrease in magnitude of voice quality changes after the intervention, indicating improvement of vocal pattern. All patients reported satisfaction and preference for telerehabilitation compared to face-to-face rehabilitation, as well as positive perception of audio and video. Some technological adversities have been identified but did not prevent the approaches to assessment and treatment. CONCLUSION: Present results suggest that telerehabilitation methods can be considered as an effective treatment for speech symptoms associated with PD and can be indicated to patients presenting limited access to speech therapy centers and technological readiness. PMID- 27191883 TI - Interference of conventional and orthodontic nipples in system stomatognatic: systematic review. AB - PURPOSE: Check if the type of nozzle, orthodontic or conventional, of pacifier and bottle have any influence on the changes found in the stomatognathic system caused by the maintenance of the sucking habit. Research Strategies: Through a systematic literature review with meta-analysis, performed from the databases Lilacs, Medline and Embase and Scholar Google, with the following key words in Portuguese and English: "malocclusion" + "Pacifiers "; "Malocclusion" + "Bottle Feeding"; "Malocclusion" + "Bottle feeding" beyond words "Orthodontic Beak" + "Conventional Beak". SELECTION CRITERIA: We included studies that presented in their methods to compare groups who used pacifiers and/or bottle with conventional nozzle with groups using orthodontic nipple without temporal delimitation. DATA ANALYSIS: The analysis of the article in its entirety was performed systematically, ordering the relevant results in the following categories: objective, method-case studies and evaluation, results, and conclusion. RESULTS: Found 1,041 jobs, from the period 1969 to 2013, 848 jobs were excluded based on the exclusion criteria and another 174 that were repetitions. A total of 19 articles were read in full of which 4 articles met the proposed inclusion criteria, and three studies were included in the meta analysis. These results show that there are no significant differences between the orthodontic and conventional nozzles on the implications of the stomatognathic system. CONCLUSION: There is no way to conclude that there are differences as to the consequences to the stomatognathic system caused by conventional nozzles and orthodontic pacifier/bottle. PMID- 27191884 TI - Vocal dose in teachers: correlation with dysphonia. AB - Teachers are professionals with high prevalence of dysphonia, whose main risk factors are the large work hours in classrooms with the presence of background noise. The purpose of the study was to calculate the phonation time and the cycle dose of teachers with dysphonia and teachers without voice disorders during the class. There were two groups analyzed: five teachers with functional dysphonia were the first group and five teachers without voice disorders were the second group. For the data was used the VoxLog(r) dosimeter and the parameters were: intensity; fundamental frequency; phonation time and cycle dose. The statistical analysis used ANOVA, Student's T-test, and Kruskal-Wallis test. Dysphonic teachers showed major values of phonation time and cycle dose compared with teachers without voice disorders. The dysphonia is related to extended period of speech time and greater exposure of the tissue of the vocal fold to phonotrauma. PMID- 27191885 TI - Jaw movement in people with Parkinson's Disease. AB - This study aimed to characterize the amplitude and speed of isolated jaw movements and chewing using electrognathography in a volunteer and to compare these data with those of two other Parkinson Disease (PD) subjects, differentiated by the motor characteristics. METHOD: The 3 participants were divided into three categories: one with 1 non-PD volunteer, a second category with 1 volunteer characterized by Parkinson's hypokinesia, and a third with 1 volunteer characterized by Parkinson's tremor. RESULTS: There were differences among the three groups; however the most significant was between the non-PD and the PD-rigidity, in the amplitude and speed when performing the jaw movements and chewing. Factors related to the adaptive and compensatory processes derived from rigidity process seemed to better explain the observed changes among the PD groups. PMID- 27191886 TI - Characteristics of young lung cancer: Analysis of Taiwan's nationwide lung cancer registry focusing on epidermal growth factor receptor mutation and smoking status. AB - Lung cancer is relatively rare in young patients as the median age at diagnosis is 65-70 years. The main objective of this nationwide study was to investigate the characteristics of young lung cancer in Taiwan, especially the relationships among smoking behavior, epidermal growth factor receptor (EGFR) mutation, and age. The National Taiwan Lung Cancer Registry, a database contain detailed cancer statistics, was analyzed in this study for the period 2011-2012. Young lung cancer was defined as age a?| 45 years. There were 21,536 lung cancer patients (13,187 men and 8349 women). Among these patients, 1074 (5.0%) were in the younger group, and 20,462 patients (95.0%) were in the older group. Female gender (48.8% versus 38.2%, P < 0.001), never-smokers (47.3% versus 43.8%, P = 0.015), and adenocarcinoma (70.4% versus 58.1%, P < 0.001) were more frequent in the younger group. While the EGFR mutation rate was lower in the younger group (52.5% versus 60.6%, P = 0.001), the primary site of lung cancer and stage distribution were not significantly different. If only adenocarcinoma patients were included in the analysis, female gender, older age, and never-smokers were more likely to have EGFR mutation. In conclusion, lung cancer in young patients (a?| 45 year old) was associated with unique characteristics, with greater percentages of female patients, adenocarcinoma, and never-smokers and a lower EGFR mutation rate compared with older patients. PMID- 27191887 TI - Circulating AR copy number and outcome to enzalutamide in docetaxel-treated metastatic castration-resistant prostate cancer. AB - In the present study, we aimed to evaluate the association of circulating AR copy number (CN) and outcome in a cohort of patients with advanced castration resistant prostate cancer (CRPC) treated with enzalutamide after docetaxel. Fifty nine CRPC patients were evaluated. AR CN was analyzed with real-time and digital PCR in the serum collected at starting of treatment. Progressive disease was defined on the basis of Prostate Cancer Working Group 2 criteria. AR CN gain was found in 21 of 59 (36%) patients. Median baseline PSA, alkaline phosphatase and lactate dehydrogenase levels were higher in the AR CN gained group (p = 0.007, p = 0.003, p = 0.0009, respectively). Median PFS of patients with AR CN gain was 2.4 (95%CI: 1.9-3.2) vs. 4.0 months (95%CI: 3.0-6.5) of those with no gain (p = 0.0004). Median OS of patients with AR CN gain was 6.1 (95%CI: 3.4-8.6) vs. 14.1 months (95%CI: 8.2-20.5) of those with no gain (p = 0.0003). At multivariate analysis, PSA decline >= 50% and AR CN showed a significant association with PFS (p = 0.008 and p = 0.002, respectively) and OS (p = 0.009 and p = 0.001, respectively). These findings indicate that the detection of circulating AR CN gain is a promising non-invasive biomarker for outcome prediction to enzalutamide treatment in CRPC patients. PMID- 27191888 TI - Long non-coding RNA metastasis associated in lung adenocarcinoma transcript 1 (MALAT1) interacts with estrogen receptor and predicted poor survival in breast cancer. AB - Metastasis associated in lung adenocarcinoma transcript 1 (MALAT1), a lncRNA that was first recognized as a prognostic parameter for patient survival of stage I lung cancer, is up-regulated in multiple human malignancies, including breast cancer. However, the mechanism of its function remained elusive. In the current study, by examining MALAT1 expression on mRNA level, we demonstrated that compared with MCF10A, MALAT1 expression was up-regulated in the majority of breast cancer cell lines (9/12). In 26 pairs of estrogen receptor (ER)-positive breast cancer samples, MALAT1 expression was significantly up-regulated compared with adjacent normal tissues (P = 0.012). Furthermore, of 204 breast cancer patients, high MALAT1 expression was associated with positive ER (P = 0.023) and progesterone receptor (PR) (P = 0.024) status. Further analysis using TCGA database revealed that ER and its target genes PGR and CCND1, were overexpressed in MALAT1 altered group compared with unaltered group, both on the mRNA and protein level. Lastly, we verified MALAT1's prognostic value in breast cancer. At the cut-off value of 75%, MALAT1 was the only independent prognostic factor of recurrence-free survival (RFS) in ER-negative patients in a multivariate Cox regression model (hazard ratio [HR] = 2.83, 95% confidence interval [CI] 1.02 7.83). MALAT1 overexpression was also associated with poor RFS in tamoxifen treated ER-positive breast cancer patients, which might serve as a potential biomarker to predict endocrine treatment sensitivity. PMID- 27191889 TI - Bi-directional roles of IRF-1 on autophagy diminish its prognostic value as compared with Ki67 in liver transplantation for hepatocellular carcinoma. AB - The prognostic values of IRF-1 and Ki-67 for liver transplantation (LT) of hepatocellular carcinoma (HCC) were investigated, as well as the mechanisms of IRF-1 in tumor suppression. Adult orthotropic liver transplantation cases (N = 127) were involved in the analysis. A significant decreased recurrence free survival (RFS) was found in the Ki-67 positive groups. Ki-67, tumor microemboli, the Milan and UCSF criteria were found to be independent risk factors for RFS. In LT for HCC beyond the Milan criteria, a significant decrease in RFS was found in the IRF-1 negative groups. In SK-Hep1 cells, an increase in apoptosis and decrease in autophagy were observed after IFN-gamma stimulation, which was accompanied with increasing IRF-1 levels. When IRF-1 siRNA or a caspase inhibitor were used, reductions in LC3-II were diminished or disappeared after IFN-gamma stimulation, suggesting that IFN-gamma inhibited autophagy via IRF-1 expression and caspase activation. However, after IRF-1 siRNA was introduced, a reduction in LC3-II was found. Thus basic expression of IRF-1 was also necessary for autophagy. IRF-1 may be used as a potential target for HCC treatment based on its capacity to affect apoptosis and autophagy. Ki-67 shows great promise for the prediction of HCC recurrence in LT and can be used as an aid in the selection of LT candidates. PMID- 27191890 TI - Molecular factors in migraine. AB - Migraine is a common neurological disorder that affects 11% of adults worldwide. This disease most likely has a neurovascular origin. Migraine with aura (MA) and more common form - migraine without aura (MO) - are the two main clinical subtypes of disease. The exact pathomechanism of migraine is still unknown, but it is thought that both genetic and environmental factors are involved in this pathological process. The first genetic studies of migraine were focused on the rare subtype of MA: familial hemiplegic migraine (FHM). The genes analysed in familial and sporadic migraine are: MTHFR, KCNK18, HCRTR1, SLC6A4, STX1A, GRIA1 and GRIA3. It is possible that migraine is a multifactorial disease with polygenic influence.Recent studies have shown that the pathomechanisms of migraine involves both factors responsible for immune response and oxidative stress such as: cytokines, tyrosine metabolism, homocysteine; and factors associated with pain transmission and emotions e.g.: serotonin, hypocretin-1, calcitonin gene-related peptide, glutamate. The correlations between genetic variants of the HCRTR1 gene, the polymorphism 5-HTTLPR and hypocretin-1, and serotonin were observed. It is known that serotonin inhibits the activity of hypocretin neurons and may affect the appearance of the aura during migraine attack.The understanding of the molecular mechanisms of migraine, including genotype-phenotype correlations, may contribute to finding markers important for the diagnosis and treatment of this disease. PMID- 27191892 TI - Distinctive expression patterns of hypoxia-inducible factor-1alpha and endothelial nitric oxide synthase following hypergravity exposure. AB - This study was designed to examine the expression of hypoxia-inducible factor 1alpha (HIF-1alpha) and the level and activity of endothelial nitric oxide synthase (eNOS) in the hearts and livers of mice exposed to hypergravity. Hypergravity-induced hypoxia and the subsequent post-exposure reoxygenation significantly increased cardiac HIF-1alpha levels. Furthermore, the levels and activity of cardiac eNOS also showed significant increase immediately following hypergravity exposure and during the reoxygenation period. In contrast, the expression of phosphorylated Akt (p-Akt) and phosphorylated extracellular signal regulated kinase (p-ERK) showed significant elevation only during the reoxygenation period. These data raise the possibility that the increase in cardiac HIF-1alpha expression induced by reoxygenation involves a cascade of signaling events, including activation of the Akt and ERK pathways. In the liver, HIF-1alpha expression was significantly increased immediately after hypergravity exposure, indicating that hypergravity exposure to causes hepatocellular hypoxia. The hypergravity-exposed livers showed significantly higher eNOS immunoreactivity than did those of control mice. Consistent with these results, significant increases in eNOS activity and nitrate/nitrite levels were also observed. These findings suggest that hypergravity-induced hypoxia plays a significant role in the upregulation of hepatic eNOS. PMID- 27191891 TI - SETD2: an epigenetic modifier with tumor suppressor functionality. AB - In the past decade important progress has been made in our understanding of the epigenetic regulatory machinery. It has become clear that genetic aberrations in multiple epigenetic modifier proteins are associated with various types of cancer. Moreover, targeting the epigenome has emerged as a novel tool to treat cancer patients. Recently, the first drugs have been reported that specifically target SETD2-negative tumors. In this review we discuss the studies on the associated protein, Set domain containing 2 (SETD2), a histone modifier for which mutations have only recently been associated with cancer development. Our review starts with the structural characteristics of SETD2 and extends to its corresponding function by combining studies on SETD2 function in yeast, Drosophila, Caenorhabditis elegans, mice, and humans. SETD2 is now generally known as the single human gene responsible for trimethylation of lysine 36 of Histone H3 (H3K36). H3K36me3 readers that recruit protein complexes to carry out specific processes, including transcription elongation, RNA processing, and DNA repair, determine the impact of this histone modification. Finally, we describe the prevalence of SETD2-inactivating mutations in cancer, with the highest frequency in clear cell Renal Cell Cancer, and explore how SETD2-inactivation might contribute to tumor development. PMID- 27191893 TI - Paclitaxel is necessary for improved survival in epithelial ovarian cancers with homologous recombination gene mutations. AB - PURPOSE: To investigate the impact of somatic mutations in homologous recombination (HR) genes on the chemotherapeutic response and survival of patients with epithelial ovarian cancer (EOC). EXPERIMENTAL DESIGN: We performed targeted massively parallel sequencing of tumor DNA from 158 patients with EOC. We associated adjuvant chemotherapy and clinical outcome with mutations in selected genes, focusing on those encoding HR proteins. RESULTS: HR mutations were found in 47 (30%) tumors. We did not detect an overall survival (OS) difference in advanced stage patients whose tumors had HR mutations compared to those without (median OS of 49.6 months (95% CI 29.9-57.7) vs. 43.3 months (95% CI 31.9-75.47), p = 0.87). However, when stratified by chemotherapy regimen, patients whose tumors had TP53 and HR mutations demonstrated a marked survival advantage when treated with platinum and paclitaxel vs. platinum +/- cyclophosphamide (median OS of 90 months (95% CI 50-NA) vs. 29.5 months (95% CI 17.7-50.5), p = 0.0005). CONCLUSIONS: Previous studies demonstrating a survival advantage for EOC patients with somatic HR mutations have been conducted with almost universal use of both platinum and paclitaxel. Our study is the first to our knowledge to compare cohorts with somatic HR gene mutations treated with and without paclitaxel containing platinum regimens. The survival benefit attributed to the platinum sensitivity of HR deficient ovarian cancers may depend upon the combined use of paclitaxel. PMID- 27191894 TI - Simultaneous multitarget radiotherapy using helical tomotherapy and its combination with sorafenib for pulmonary metastases from hepatocellular carcinoma. AB - We evaluated radiotherapy using helical tomotherapy (HT) combined with sorafenib for treatment of pulmonary metastases from hepatocellular carcinoma (HCC). We also analyzed potential prognostic factors and further validated the combination treatment. The objective response rate in the total cohort of 45 patients treated with HT (with or without sorafenib) was 66.7% (complete response, n = 1; partial response, n = 29), with no adverse events > grade 2 in severity. Median progression-free survival (PFS) and overall survival (OS) were 7.50 +/- 0.53 and 26.40 +/- 2.66 months, respectively. The addition of sorafenib was associated with increased PFS (11.80 +/- 1.55 vs 5.80 +/- 0.52 months, p = 0.006) and increased OS (29.60 +/- 5.23 vs 21.90 +/- 5.17 months, p = 0.007). After multivariate adjustment, the risk of disease progression associated with combination treatment was significantly lower (p = 0.022) compared with HT only, and survival was significantly longer (p = 0.014). Further validation confirmed the benefit of combination treatment. Prognostic factors were number of pulmonary metastases for PFS (19.00 +/- 7.15 months for <=3 lesions vs 5.80 +/- 0.26 months for >3 lesions, p < 0.001) and intrahepatic tumor status for OS (28.50 +/- 2.76 months for well-controlled tumors vs 15.60 +/- 6.38 months for uncontrolled tumors, p = 0.011). In conclusion, radiotherapy with HT for pulmonary metastases is feasible without major complications, and its combination with sorafenib may be a promising approach in a subgroup of patients. PMID- 27191896 TI - Binding Strength of Nucleobases and Nucleosides on Silver Nanoparticles Probed by a Colorimetric Method. AB - Because of their unique and tunable properties, oligonucleotide-functionalized noble metal nanoparticles have provided a versatile platform for various engineering and biomedical applications. The vast majority of such applications were demonstrated with gold nanoparticles (AuNPs) while only a few were demonstrated with sliver nanoparticles (AgNPs). This is largely due to the lack of robust protocols to functionalize AgNPs with thiol-modified oligonucleotides. Previous studies have revealed strong interactions between nucleobases and AgNPs. This could enable an alternative way to functionalize AgNPs with non-thiolated oligonucleotides. However, there is no quantitative study on the interaction strengths between AgNPs and oligonucleotides. Several methods have been used for quantitative evaluation of the interaction strengths between AuNPs and oligonucleotides. These methods often require specialized equipment that might not be widely accessible or rely on labor-intensive procedures to obtain the adsorption isotherms. Herein, we developed a colorimetric method, as a simple and high-throughput alternative of existing methods, to quantify the binding strength between AgNPs and nucleobases/nucleosides. In this colorimetric method, concentration-dependent destabilizing effects of nucleobase/nucleoside adsorption on AgNPs are utilized to indirectly quantify the amount of nucleobases/nucleosides adsorbed on AgNPs, thus deriving the binding strength between AgNPs and nucleobases/nucleosides. First, the concentration-dependent AgNP aggregation kinetics in the presence of nucleobases/nucleosides were systematically investigated. Then, this colorimetric method was used to determine the binding strengths between AgNPs and various DNA/RNA nucleobases/nucleosides. It was found that the ranking of interaction strengths between AgNPs and DNA/RNA nucleosides (dC < dT < dA, rC < rU < rA) is generally agreed with that between AgNPs and corresponding nucleobases (C < T < U < A). This suggests that DNA/RNA nucleosides interact with AgNPs mainly via the constituent nucleobases. It was also revealed that interactions of AgNPs with DNA/RNA nucleosides are significantly weaker than that with corresponding nucleobases. This implies that deoxyribose/ribose might sterically inhibit the interactions between nucleobases and AuNPs. PMID- 27191895 TI - A novel TRPV4-specific agonist inhibits monocyte adhesion and atherosclerosis. AB - TRPV4 ion channel mediates vascular mechanosensitivity and vasodilation. Here, we sought to explore whether non-mechanical activation of TRPV4 could limit vascular inflammation and atherosclerosis. We found that GSK1016790A, a potent and specific small-molecule agonist of TRPV4, induces the phosphorylation and activation of eNOS partially through the AMPK pathway. Moreover, GSK1016790A inhibited TNF-alpha-induced monocyte adhesion to human endothelial cells. Mice given GSK1016790A showed increased phosphorylation of eNOS and AMPK in the aorta and decreased leukocyte adhesion to TNF-alpha-inflamed endothelium. Importantly, oral administration of GSK1016790A reduced atherosclerotic plaque formation in ApoE deficient mice fed a Western-type diet. Together, the present study suggests that pharmacological activation of TRPV4 may serve as a potential therapeutic approach to treat atherosclerosis. PMID- 27191901 TI - Doctor to Doctor. PMID- 27191897 TI - The effects of the 5-HT2A receptor antagonist sarpogrelate hydrochloride on chronic hypoxic pulmonary hypertension in rats. AB - PURPOSE OF THE STUDY: This study investigated whether sarpogrelate hydrochloride (SPG), a 5-HT2A receptor antagonist, alleviates chronic hypoxic pulmonary hypertension (CH-PH) in rats by stimulating apoptosis and inhibiting proliferation in pulmonary artery smooth muscle cells (PASMCs). MATERIALS AND METHODS: Forty male Sprague-Dawley rats were pretreated with SPG (50 mg/kg/day by oral gavage) or saline vehicle and then subjected to chronic hypoxia (CH) (hypobaric chamber set to 380 mmHg, 10% oxygen) or normoxia for 14 days. Mean pulmonary artery pressure (PAP) and right ventricular hypertrophy (RVH) were measured. Hypertensive pulmonary vascular remodeling was assayed by light microscopy. Terminal deoxynucletidyl transferase dUTP nick end ligase (TUNEL) assays, western blotting, and real-time polymerase chain reaction were used to assess apoptosis, proliferation and underlying signaling pathways in PASMCs from lung tissue and isolated pulmonary artery rings. RESULTS: CH increased mean PAP and RVH. CH increased the percentage of muscularized arteries in the peripheral pulmonary vasculature and medial wall thickness in small muscular arteries. CH increased pulmonary protein and mRNA levels of the B-cell lymphoma protein 2 (Bcl 2), pyruvate dehydrogenase kinase (PDK), phosphorylation of extracellular signal regulated kinases 1 and 2 (pERK1/2), cyclin D1, proliferating cell nuclear antigen (PCNA) and decreased protein and mRNA levels of Bcl-2-associated X protein (BAX), cleaved caspase-3. Pretreatment with SPG, which has been shown previously to inhibit ERK1/2 phosphorylation and PDK, countered all of these effects. Isolated pulmonary artery rings incubated with 5-HT increased pERK1/2, PDK, and Bcl-2 expression, and decreased Bax expression. CONCLUSION: Administration of SPG ameliorated the development of CH-PH by stimulating apoptosis in and inhibiting proliferation of PASMCs. PMID- 27191902 TI - Checks and Balances. PMID- 27191904 TI - Bernstein's hug. PMID- 27191903 TI - The Medical Bookshelf. PMID- 27191905 TI - Chronic lung disease. PMID- 27191907 TI - Primary Care Digest. PMID- 27191906 TI - Prevention of emphysema. PMID- 27191909 TI - Emphysema. PMID- 27191911 TI - Emperipolesis in eosinophilic granuloma of the skull. PMID- 27191910 TI - Resveratrol-Loaded Liquid-Crystalline System Inhibits UVB-Induced Skin Inflammation and Oxidative Stress in Mice. AB - Evidence shows beneficial effects of resveratrol (RES) on human health. However, its poor aqueous solubility limits therapeutic effectiveness. Thus, the use of nanostructured delivery systems for RES, such as a liquid-crystalline system (LCS), could be viable. The purpose of this study was to develop, characterize, and determine the in vivo effectiveness of a RES-loaded LCS. We studied an LCS containing silicon glycol copolymer, polyether functional siloxane, and the polymeric dispersion carbomer homopolymer type B (C974) in the ratio 20:55:25 with and without RES. Results obtained using polarized light microscopy, small angle X-ray scattering, and rheology analysis showed that the RES-loaded LCS system presents a lamellar structure and behaves as a non-Newtonian fluid presenting pseudoplastic (the apparent viscosity decreases as the stress increases) and thixotropic (the apparent viscosity decreases with the duration of stress) behaviors. Cytotoxicity studies showed that the formulation components are noncytotoxic. Topical application of a RES-loaded LCS protected hairless mice from UVB-irradiation-induced skin damage by inhibiting edema, neutrophil recruitment, lipid hydroperoxide and superoxide anion production, gp91phox mRNA expression, and oxidative stress. The RES-loaded LCS maintained 2,2'-azinobis(3 ethylbenzothiazoline-6-sulfonic acid) (ABTS) and ferric reducing abilities, catalase activity, reduced glutathione levels, and mRNA expression of glutathione peroxidase 1 and glutathione reductase. The RES-loaded LCS also up-regulated matrix metalloproteinase-9 activity, IL-10 production, and mRNA expression of transcription factor Nrf2 and heme oxygenase-1. Therefore, a RES-loaded LCS is a promising new therapeutic approach to mitigate skin photodamage. PMID- 27191912 TI - A methodological study of locus coeruleus degeneration in dementing disorders. AB - BACKGROUND: Degeneration of the locus coeruleus (LC) of the brain stem is a recognized phenomenon in Alzheimer's disease (AD), in dementia with Lewy bodies (DLB), and in Parkinson's disease with dementia (PDD). Prior studies have suggested that LC degeneration can be used to differentiate various dementing disorders histologically, but the paucity of methodological data may hamper systematic research on this nucleus. PURPOSE: The purpose of this study was to evaluate various approaches to quantifying LC degeneration in dementing disorders, and to inform future decisions regarding the most appropriate method for diagnostics and research. METHODS: 105 LCs from brains of demented individuals with AD, DLB/PDD, vascular dementia (VaD), mixed dementia (AD+VaD), or frontotemporal lobar degeneration (FTLD) were examined, and the extent of LC degeneration was assessed using macroscopic evaluation, cell counting, and two degeneration scales. Scores were compared across diagnostic categories; diagnostic utility and intra- and interobserver reliability were assessed. RESULTS: AD and DLB/PDD were associated with greater LC damage using either assessment method, significantly different from VaD and FTLD. Macroscopic appearance was informative, but cell counting was more sensitive and specific. The degeneration scales did not add significant diagnostic value over cell counting and were associated with greater observer variability. CONCLUSIONS: The LC degenerates in certain dementia subtypes, especially in AD and DLB/PDD. Macroscopic assessment of the LC postmortem can be used to differentiate between disorders associated with degeneration (AD, DLB/PDD) or sparing (VaD) of the LC, but counting LC cells in a representative pontine section is the most appropriate method by which to assess LC degeneration. PMID- 27191913 TI - Microglioma in a child - a further case in support of the microglioma entity and distinction from histiocytic sarcoma. AB - Microglia are not generally known to cause brain tumors but one bona fide case of adult microglioma has been published [9]. This tumor was highly malignant. We now report on a second, juvenile case, which showed a less aggressive course. Microglioma is a primary central nervous system (CNS) neoplasm distinct from glioma and other known brain tumor entities, based on its strong immunoreactivity for the macrophage marker CD163, the microglia marker Iba1, and the complete absence of neural as well as lymphocyte antigens. Furthermore, we have analyzed the literature and identified a number of cases that qualify as primary parenchymal histiocytic sarcomas of the CNS, which lack microglial morphology. Considering the non-hematopoietic developmental origin of the vast majority of microglia and the distinct morphological as well as immunophenotypic similarity of their neoplastic counterparts, we suggest using the term microglioma. More cases will be required along with appropriately-collected tissue to establish the molecular genetic profile of this extremely rare entity. PMID- 27191914 TI - Hyaline protoplasmic astrocytopathy with associated focal cortical dysplasia and hippocampal sclerosis. AB - Hyaline protoplasmic astrocytopathy is a rare histopathologic finding in which there is an accumulation of filamin A within protoplasmic astrocytes. The condition has been reported in association with Aicardi syndrome and in patients with epilepsy. This case reports findings of hyaline protoplasmic astrocytopathy in a 4-year-old female who presented with febrile-onset, medically-intractable epilepsy. She underwent resection of the left lateral temporal lobe, hippocampus, and amygdala. In addition to characteristic eosinophilic, astrocytic cytoplasmic inclusions, the lateral temporal lobe showed changes consistent with ILAE (International League Against Epilepsy) type Ic focal cortical dysplasia/Palmini et al. [12] type IA focal cortical dysplasia. The hippocampal formation was marked by loss of neurons in the CA1 region accompanied by gliosis and a relative sparing of neurons in the CA4 region, consistent with ILAE type 2 hippocampal sclerosis or CA1 sclerosis. The literature on hyaline protoplasmic astrocytopathy and coexistent pathologies in the clinical setting of chronic epilepsy is reviewed. PMID- 27191915 TI - Extracellular vesicles in blood, milk and body fluids of the female and male urogenital tract and with special regard to reproduction. AB - Extracellular vesicles (EVs) are released from almost all cells and tissues. They are able to transport substances (e.g. proteins, RNA or DNA) at higher concentrations than in their environment and may adhere in a receptor-controlled manner to specific cells or tissues in order to release their content into the respective target structure. Blood contains high concentrations of EVs mainly derived from platelets, and, at a smaller amount, from erythrocytes. The female and male reproductive tracts produce EVs which may be associated with fertility or infertility and are released into body fluids and mucosas of the urogenital organs. In this review, the currently relevant detection methods are presented and critically compared. During pregnancy, placenta-derived EVs are dynamically detectable in peripheral blood with changing profiles depending upon progress of pregnancy and different pregnancy-associated pathologies, such as preeclampsia. EVs offer novel non-invasive diagnostic tools which may reflect the situation of the placenta and the foetus. EVs in urine have the potential of reflecting urogenital diseases including cancers of the neighbouring organs. Several methods for detection, quantification and phenotyping of EVs have been established, which include electron microscopy, flow cytometry, ELISA-like methods, Western blotting and analyses based on Brownian motion. This review article summarises the current knowledge about EVs in blood and cord blood, in the different compartments of the male and female reproductive tracts, in trophoblast cells from normal and pre eclamptic pregnancies, in placenta ex vivo perfusate, in the amniotic fluid, and in breast milk, as well as their potential effects on natural killer cells as possible targets. PMID- 27191917 TI - Clinical Problem Solving Series Strategies of Information Gathering. AB - EDITORS' PREFACE Our goal in this exercise is to consider a neglected aspect of diagnostic problem solving, namely the strategies that physicians use to gather data as they confront a diagnostic dilemma. In the first part, we will analyze the rationale for individual questions and for the sequence of questions that a general internist used when taking the history from a previously ill physician. In the second part, we will review some of the studies that bear on the experimental approach to information gathering. PMID- 27191916 TI - The active immunological profile in patients with primary Sjogren's syndrome is restricted to typically encountered autoantibodies. PMID- 27191918 TI - Abstracts of the meeting of the Belgian Society of Internal Medicine (5 May 1990). PMID- 27191920 TI - Histologic evaluation of new bone in post-extraction sockets induced by melatonin and apigenin: an experimental study in American fox hound dogs. AB - OBJECTIVE: The aim of this study was to evaluate the effect of topical applications of melatonin and apigenin (4',5,7-trihydroxyflavone) on new bone formation in post-extraction sockets after 30, 60 and 90 days. MATERIALS AND METHODS: Six American fox hounds were used in the study, extracting mandibular premolars (P2, P3 and P4) and first molar (M1). Melatonin or apigenin impregnated in collagen sponges were applied at P3, P4 and M1 sites in both hemimandibles; P2 sites were used as control sites. Bone biopsies were taken at 30, 60 and 90 days and stained with hematoxylin-eosin. RESULTS: At 30 days, a higher percentage of immature bone was observed in the control group (58.11 +/- 1.76%) than in the apigenin (34.11 +/- 1.02%) and melatonin groups (24.9 +/- 0.14%) with significant differences between the three groups (P < 0.05). At 60 days, results were significantly better at melatonin sites (10.34 +/- 1.09%) than apigenin (19.22 +/ 0.35%) and control sites (36.7 +/- 1.11%) (P < 0.05). At 90 days, immature bone percentages were similar for all groups. New bone formation was higher in melatonin group (79.56 +/- 1.9%) than apigenin (68.89 +/- 1.5%) and control group (58.87 +/- 0.12%). CONCLUSIONS: Topical applications of either melatonin or apigenin have a potential to accelerate bone tissue in early healing stages; melatonin was seen to have stimulated bone maturation to a greater extent at the 60 days of follow-up. PMID- 27191921 TI - Peritonsillar morphine infiltration to prevent early postoperative pain after tonsillectomy. PMID- 27191922 TI - Gender difference in career advancement and job satisfaction in anaesthesia: A cross-sectional study. PMID- 27191923 TI - Effects of remifentanil on pharyngeal swallowing: A double blind randomised cross over study in healthy volunteers. AB - BACKGROUND: Exposure to remifentanil increases the incidence of pulmonary aspiration in healthy volunteers. This effect may be explained by impairment of airway defence mechanisms and/or altered swallowing function. Pressure-flow analysis is a technique that allows objective assessment of swallowing based on pressure-impedance patterns recorded during bolus swallowing. OBJECTIVES: The aim of this study was to use pressure-flow analysis to quantify the effect of remifentanil on healthy pharyngeal swallowing and to compare these effects with morphine. DESIGN: A double-blind, randomised, cross-over study. SETTING: A tertiary care teaching hospital. VOLUNTEERS: Eleven young volunteers (mean age, 23 years) and seven older volunteers (mean age, 73 years). INTERVENTIONS: Volunteers were studied twice and received either a target-controlled remifentanil infusion (target concentrations: young, 3 ng ml; old, 2 ng ml) or a bolus injection of morphine (dose: young, 0.1 mg kg; old, 0.07 mg kg). Pharyngeal pressure and impedance were recorded with an indwelling catheter while swallowing 10 boluses of liquid during each measuring phase. Variables defining swallowing function were calculated and compared to determine drug effects. MAIN OUTCOME MEASURES: Pharyngeal pressure-flow variables following remifentanil exposure. RESULTS: Changes produced by remifentanil in the measured variables were consistent with greater dysfunction of swallowing. Both the strength of the pharyngeal contractions and pharyngeal bolus propulsion were reduced, whereas flow resistance was increased. The swallow risk index, a global index of swallowing dysfunction, increased overall. At the experimental doses tested, morphine produced similar, but less extensive effects on swallowing. CONCLUSION: Remifentanil induced dysfunction of the pharyngeal swallowing mechanism. This may contribute to an increased risk of aspiration. TRIAL REGISTRATION: NCT01924234 (www.clinicaltrials.gov). PMID- 27191924 TI - Reply to: are transdermal opioids contraindicated in patients at risk of suicide? PMID- 27191926 TI - Perioperative nurses' attitudes towards organ procurement: a systematic review. AB - AIMS AND OBJECTIVES: To explore and evaluate perioperative nurses' experience of organ procurement. BACKGROUND: Organ procurement is part of the organ donation process, and is typically performed in the perioperative setting. This experience may contribute to perioperative nurses' feelings of distress and negative attitudes towards organ donation. DESIGN: Systematic review of the literature. METHOD: Primary research studies, published in the English language between 1990 2014 were identified, screened and appraised using Joanna Briggs Institute appraisal tools. Data extraction and analysis followed. RESULTS: The quality assessment resulted in seven qualitative and three quantitative research studies. The main findings were: (1) Perioperative nurses reported feeling emotionally distressed, challenged, lonely and physically drained throughout the entire organ procurement procedure. (2) Perioperative nurses reported finding their own unique self-coping strategies and ways of eliciting support. (3) Perioperative nurses had positive and negative attitudes towards organ donation. CONCLUSION: Perioperative nurses reported feelings of sadness, feeling challenged and physically drained through the entire organ procurement procedure, which were influenced by differing factors in the preoperative, intraoperative and postoperative stages. It is acknowledged that personal coping strategies and support are important to help perioperative nurses improve their psychological well-being, and their experiences and attitudes towards organ procurement and donation. The meaningfulness of these findings for practice policy and research is described. RELEVANCE TO CLINICAL PRACTICE: Perioperative nurses play a vital role in the organ procurement procedure and require ongoing support to ensure their psychological welfare, in particular, newly qualified or inexperienced nurses' participating in organ procurement. PMID- 27191925 TI - The influence of a dynamic elastic garment on musculoskeletal and respiratory wellness in computer users. AB - BACKGROUND: Evidence is growing that computer users are at increased risk of developing musculoskeletal disorders, particularly those involving the upper extremity, with significant financial cost and lost productivity. OBJECTIVE: The purpose of this study was to determine the short-term effects of wearing a dynamic elastic garment (Posture Shirt[Formula: see text]; AlignMed, USA) on musculoskeletal wellness and health in the computer workplace. METHODS: Ninety six computer users were evaluated. The Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire was completed. A functional assessment of posture, lung function, and grip strength was performed after wearing the Posture Shirt[Formula: see text] for 4 weeks. A training log was kept to track usage of the garment, as well as weekly sensations of fatigue, productivity, and energy level. RESULTS: After 4 weeks, there was statistically significant improvement in forward shoulder and head posture, thoracic kyphosis, and grip strength. Improvements in spirometry measures did not meet statistical significance. Postural fatigue and muscular fatigue decreased by 21% and 29%, respectively, and energy level and productivity increased by 20% and 13%, respectively. CONCLUSION: This prospective study demonstrated positive short-term impact of the Posture Shirt[Formula: see text] on both subjective and objective measures of posture, lung function, grip strength, fatigue, and productivity. PMID- 27191927 TI - Glaucoma with Descemet's membrane detachment in five horses. AB - PURPOSE: To describe the clinical and histopathologic features of glaucoma associated with Descemet's membrane (DM) detachment in five horses without prior history of intraocular surgery. ANIMALS STUDIED: Three Appaloosa horses and two Thoroughbreds were included in this study. The affected horses ranged in age from 16 to 27 years and presented with severe diffuse corneal edema. PROCEDURE: Five eyes were enucleated due to intraocular hypertension and/or chronic corneal ulceration. The enucleated globes were evaluated by the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW). Each globe was routinely processed for histopathology and analyzed by light microscopy. A histologic diagnosis of glaucoma was reached by demonstrating a loss of optic nerve axonal tissue by measuring neurofilament-immunopositive axons with automated image analysis software. RESULTS: All five horses presented with unilateral severe diffuse corneal edema that had developed between 2 and 16 weeks prior to enucleation. Intraocular pressures for the affected eyes were between 9 and 87 mmHg prior to enucleation. Descemet's membrane detachment was identified histopathologically in all five globes (5/5, 100%). All five eyes had an avascular spindle cell proliferation filling the space between the displaced peripheral DM and the corneal stroma. Neurofilament immunostaining revealed axonal loss consistent with glaucoma. CONCLUSION: Equine glaucoma may be associated with Descemet's membrane detachment. This detachment and glaucoma is a possible differential diagnosis for severe equine corneal edema. In this case series, an eye with a DM detachment had a poor prognosis for retention. PMID- 27191928 TI - Headaches and myofascial temporomandibular disorders: overlapping entities, separate managements? AB - There are relevant clinical overlaps between some of the painful temporomandibular disorders (TMD) and headache conditions that may hamper the diagnostic process and treatment. A non-systematic search for studies on the relationship between TMD and headaches was carried out in the following databases: PubMed, Cochrane Library and Embase. Important pain mechanisms contributing to the close association and complex relationship between TMD and headache disorders are as follows: processes of peripheral and central sensitisation which take place in similar anatomical areas, the possible impairment of the descending modulatory pain pathways and the processes of referred pain. In addition, the clinical examination does not always provide distinguishing information to differentiate between headaches and TMD. So, considering the pathophysiology and the clinical presentation of some types of headache and myofascial TMD, such overlap can be considered not only a matter of comorbid relationship, but rather a question of disorders where the distinction lines are sometimes hard to identify. These concerns are certainly reflected in the current classification systems of both TMD and headache where the clinical consequences of diagnosis such as headache attributed to or associated with TMD are uncertain. There are several similarities in terms of therapeutic strategies used to manage myofascial TMD and headaches. Considering all these possible levels of interaction, we reinforce the recommendation for multidisciplinary approaches, by a team of oro-facial pain specialists and a neurologist (headache specialist), to attain the most precise differential diagnosis and initiate the best and most efficient treatment. PMID- 27191929 TI - Sendai viroplexes for epidermal growth factor receptor-directed delivery of interleukin-12 and salmosin genes to cancer cells. AB - BACKGROUND: The effective delivery of therapeutic genes to target cells has been a fundamental goal in cancer gene therapy because of its advantages with respect to both safety and transfection efficiency. In the present, study we describe a tumor-directed gene delivery system that demonstrates remarkable efficacy in gene delivery and minimizes the off-target effects of gene transfection. METHODS: The system consists of a well-verified cationic O,O'-dimyristyl-N-lysyl glutamate (DMKE), Sendai virus fusion (F) protein and hemagglutinin-neuraminidase (HN) protein, referred to as cationic Sendai F/HN virosomes. To achieve tumor-specific recognition, anti-epidermal growth factor (EGF) receptor antibody was coupled to the surface of the virosomes containing interleukin-12 (IL-12) and/or salmosin genes that have potent anti-angiogenetic functions. RESULTS: Among the virosomal formulations, the anti-EGF receptor (EGFR) viroplexes, prepared via complexation of plasmid DNA (pDNA) with cationic DMKE lipid, exhibited more efficient gene transfection to tumor cells over-expressing EGF receptors compared to the neutrally-charged anti-EGFR virosomes encapsulating pDNA. In addition, the anti EGFR viroplexes with IL-12 and salmosin genes exhibited the most effective therapeutic efficacy in a mouse tumor model. Especially when combined with doxorubicin, transfection of the two genes via the anti-EGFR viroplexes exhibited an enhanced inhibitory effect on tumor growth and metastasis in lungs. CONCLUSIONS: The results of the present study suggest that anti-EGFR viroplexes can be utilized as an effective strategy for tumor-directed gene delivery. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27191930 TI - Relationship between the apolipoprotein E gene and headache following sports related concussion. AB - INTRODUCTION: Headache is one of the most commonly reported and longest lasting symptoms that concussed athletes report, yet the etiology of headache symptoms following concussion is not entirely clear. The purpose of this study was to determine whether the e4 allele of the apolipoprotein E (APOE) gene influences the presence and severity of postconcussion headache. METHOD: Participants were composed of 45 concussed athletes and 43 healthy/nonconcussed athletes who were involved in a clinically based sports concussion management program. All athletes completed the Post-Concussion Symptom Scale (PCSS). The "headache" symptom from the PCSS was the primary outcome variable. Buccal samples were collected and analyzed to determine APOE genotype. RESULTS: A significantly greater proportion of concussed e4+ athletes than e4- athletes endorsed headache. Furthermore, concussed e4+ athletes endorsed more severe headaches than e4- athletes. When examining the healthy/nonconcussed sample (i.e., athletes at baseline), results showed no differences between e4 allele groups with respect to the presence and severity of headache. CONCLUSIONS: These findings show that when compared to concussed e4- athletes, e4+ athletes are more likely to (a) endorse postconcussion headache and (b) report more severe headache symptoms following concussion. Conversely, it appears that the e4 allele does not influence baseline reports of headache. Thus, results suggest that those with the e4 genotype may be at a higher risk for experiencing headache-related difficulties only after a concussion is sustained. PMID- 27191932 TI - Congenital lacrimal fistula: A major review. AB - The purpose of this article is to review and summarize the etiopathogenesis, symptomatology, systemic associations, management, complications and clinical outcomes of congenital lacrimal fistulae. The authors performed an electronic database (PubMed, MEDLINE, EMBASE and Cochrane Library) search of all articles published in English on congenital lacrimal fistulae. Congenital subsets of patients from series of mixed lacrimal fistulae were included in the review. These articles were reviewed along with their relevant cross-references. Data reviewed included demographics, presentations, investigations, management, complications and outcomes. The prevalence of congenital lacrimal fistulae is reported to be around 1 in 2000 live births. They are frequently unilateral, although familial cases tend to be bilateral. Lacrimal and systemic anomalies have been associated with lacrimal fistulae. Exact etiopathogenesis is unknown but mostly believed to be an accessory out budding from the lacrimal drainage system during embryogenesis. Treatment is indicated when significant epiphora or discharge is present and is mostly achieved by various fistulectomy techniques with or without a dacryocystorhinostomy. Congenital lacrimal fistulae are a distinct clinical entity with unique features. Surgical management can be challenging and successful outcomes are usually achieved with widely accepted protocols. PMID- 27191931 TI - Compressing molecular dynamics trajectories: Breaking the one-bit-per-sample barrier. AB - Molecular dynamics simulations yield large amounts of trajectory data. For their durable storage and accessibility an efficient compression algorithm is paramount. State of the art domain-specific algorithms combine quantization, Huffman encoding and occasionally domain knowledge. We propose the high resolution trajectory compression scheme (HRTC) that relies on piecewise linear functions to approximate quantized trajectories. By splitting the error budget between quantization and approximation, our approach beats the current state of the art by several orders of magnitude given the same error tolerance. It allows storing samples at far less than one bit per sample. It is simple and fast enough to be integrated into the inner simulation loop, store every time step, and become the primary representation of trajectory data. (c) 2016 Wiley Periodicals, Inc. PMID- 27191933 TI - Improved minimal residual disease detection by targeted quantitative polymerase chain reaction in Nucleophosmin 1 type a mutated acute myeloid leukemia. AB - Multicolor flow cytometry (MFC) and real-time quantitative PCR (RQ-PCR) are important independent techniques to determine minimal residual disease (MRD) in acute myeloid leukemia (AML). MFC is the standard method, but may be unreliable. Therefore, MFC-based determination of MRD with an RQ-PCR-based approach targeting the nucleophosmin 1 (NPM1) type A mutation was set out to compare. Since most current NPM1 RQ-PCR MRD protocols suffer from clear definitions of quantifiability, we sought to define quantifiability in a reproducible and standardized manner. The limit of quantifiability of our RQ-PCR protocol for the NPM1 type A mutation varied between 0.002% and 0.04% residual leukemic cells depending on the features of the standard curve for each PCR experiment. The limit of detection was close to 0.001% leukemic cells. The limit of detection by MFC ranged from 0.01% to 1% depending on the phenotype of the leukemic cells as compared with non-leukemic bone marrow cells. Forty-five MRD samples from 15 patients using both NPM1 mutation specific RQ-PCR and MFC were analyzed. In 32 of the 45 samples (71%), an MRD-signal could be detected with RQ-PCR. A quantifiable NPM1 mutation signal was found in 15 samples (33%) (range 0.003%-2.6% leukemic cells). By contrast, only two follow-up samples (4%) showed residual leukemic cells (0.04% and 0.3%, respectively) by MFC. Thus, RQ-PCR of the NPM1 type A mutation was more sensitive and reliable than MFC for determination of MRD, which might have clinical implications. (c) 2016 Wiley Periodicals, Inc. PMID- 27191935 TI - Enhanced hyphal growth of arbuscular mycorrhizae by root exudates derived from high R/FR treated Lotus japonicus. AB - Red/Far Red (R/FR) sensing positively influences the arbuscular mycorrhizal (AM) symbiosis of both legume and nonlegume plants through jasmonic acid (JA) and strigolactone signaling. We previously reported that root exudates obtained from high R/FR-grown plants contained more strigolactone than low R/FR-grown plants. To determine whether JA and JA derivatives were secreted from roots, we investigated the expression levels of JA-responsive genes in L. japonicus Miyakojima MG20 plants treated with root exudates prepared from either high or low R/FR light-treated plants. The root exudates from high R/FR light-treated plants were found to enhance the expression levels of JA-responsive genes significantly. Moreover, exogenous JA increased AM fungal hyphal elongation as did the root exudates derived from high R/FR-grown L. japonicus plants. We conclude that increased JA accumulation and secretion into root exudates from high R/FR light-grown plants is the best explanation for increased colonization and enhanced mycorrhization under these conditions. PMID- 27191937 TI - lambda-Eye: a high-sensitivity gamma imaging probe for axillary sentinel lymph node mapping. AB - OBJECTIVE: The aim of this study is the construction and performance evaluation of 'lambda-eye', a gamma imaging probe, optimized in terms of sensitivity for sentinel lymph node mapping. The optimization of the probe is based on theoretical models and simulation results that were presented in a previous study of our group. In this work, the construction of the probe, the experimental confirmation of the simulation results, and the evaluation of its performance with phantoms and lymph node imaging in small animals are presented. METHODS: The system's spatial and energy resolution, sensitivity, and count rate performance were measured using phantoms. The values of the integral and differential uniformity in the useful field-of-view and in the central field-of-view were also calculated. Finally, a proof-of-concept animal experiment was conducted for the imaging of the lymph nodes of normal mice. RESULTS: The system's energy resolution was measured as 36+/-2% and the spatial resolution was 2.2 mm at 2 mm source-collimator distance. The values of the integral uniformity and differential uniformity in the useful field-of-view and in the central field-of view were found to be 5.2, 2.1, 1.7, and 0.75%, respectively. Finally, the lymph nodes of normal mice were clearly imaged with a 10 s acquisition time. CONCLUSION: The 'lambda-eye', used for sentinel lymph node mapping, provides a combination of high sensitivity (~1.5 counts/s/kBq) and good spatial resolution (~6 mm full-width of the half-maximum at 20 mm and ~10 mm full-width of the half maximum at 50 mm distance). Its compact size (40 mm*40 mm*70 mm) allows its use during surgery and/or for the detailed scan of a suspicious region. PMID- 27191934 TI - Human Infection with Influenza A(H7N9) Virus during 3 Major Epidemic Waves, China, 2013-2015. AB - Since March 2013, a novel influenza A(H7N9) virus has caused 3 epidemic waves of human infection in mainland China. We analyzed data from patients with laboratory confirmed influenza A(H7N9) virus infection to estimate the risks for severe outcomes after hospitalization across the 3 waves. We found that hospitalized patients with confirmed infections in waves 2 and 3 were younger and more likely to be residing in small cities and rural areas than were patients in wave 1; they also had a higher risk for death, after adjustment for age and underlying medical conditions. Risk for death among hospitalized patients during waves 2 and 3 was lower in Jiangxi and Fujian Provinces than in eastern and southern provinces. The variation in risk for death among hospitalized case-patients in different areas across 3 epidemic waves might be associated with differences in case ascertainment, changes in clinical management, or virus genetic diversity. PMID- 27191936 TI - Evaluation of the effectiveness of adding androgen deprivation to modern dose escalated radiotherapy for men with favorable intermediate-risk prostate cancer. AB - BACKGROUND: Randomized trials have shown that androgen-deprivation therapy (ADT) improves survival for men with intermediate-risk prostate cancer treated with radiotherapy (RT). The benefit of ADT to patients with favorable intermediate risk prostate cancer treated with modern dose-escalated RT is unknown. This study evaluated the effectiveness of ADT on survival of men with favorable intermediate risk prostate cancer treated with dose-escalated RT. METHODS: This study was a retrospective cohort analysis of men with favorable intermediate-risk prostate cancer from 2004 to 2007 in the National Cancer Data Base. Favorable intermediate risk disease was defined as 1 adverse risk factor (prostate-specific antigen level of 10-20 ng/mL or Gleason score of 7) and clinical T1/T2 prostate cancer. All patients were treated with primary dose-escalated RT (>=75.6 Gy or RT with a brachytherapy boost). Overall survival was analyzed with propensity score adjustment and Cox multivariate modeling. RESULTS: The study included 18,598 patients. The use of ADT decreased from 43.5% in 2004 to 39.5% in 2007. The propensity score-adjusted survival analysis demonstrated similar 8-year overall survival for men treated with dose-escalated RT and ADT and men treated with RT alone (77.7% vs 78.4%). ADT was not associated with improved survival in any age or comorbidity subgroup. In a sensitivity analysis using Cox multivariate modeling, the receipt of ADT was not associated with overall survival (hazard ratio, 0.99; 95% confidence interval, 0.91-1.07; P = .768). CONCLUSIONS: Adding ADT to modern dose-escalated RT was not associated with improved survival for patients with favorable intermediate-risk prostate cancer. The applicability of the survival benefit seen in older trials to modern patients is unclear. Because of the morbidity associated with ADT, dose-escalated RT alone for patients with favorable intermediate-risk prostate cancer may be a reasonable option. Cancer 2016;122:2341-2349. (c) 2016 American Cancer Society. PMID- 27191938 TI - Hydrophobin-1 promotes thermostability of firefly luciferase. AB - The thermal sensitivity of firefly luciferase limits its use in certain applications. Firefly luciferase has hydrophobic sites on its surface, which lead to aggregation and inactivation of the enzyme at temperatures over 30 degrees C. We have successfully stabilized firefly luciferase at high temperatures with the assistance of a unique protein, hydrophobin-1 (HFB1). HFB1 is a small secretory protein belonging to class II of hydrophobins with a low molecular weight (7.5 kDa) and distinct functional hydrophobic patch on its surface. The interaction of HFB1 with hydrophobic sites on the surface of luciferase was confirmed by extrinsic fluorescence studies using 8-anilino-1-naphthalenesulfonic acid (ANS) as a hydrophobic reporter probe. Calculation of thermodynamic parameters of heat inactivation of luciferase shows that conformational changes and flexibility of enzyme decreased in the presence of HFB1, and thermostability of the HFB1-treated enzyme increased. Furthermore, the addition of HFB1 into the enzymatic solution leads to an increase in catalytic efficiency of luciferase and subsequently improves the utility of the enzyme as an ATP detector. PMID- 27191939 TI - Treatment Options for Veterans With Posttraumatic Stress Disorder-Reply. PMID- 27191940 TI - Individual differences in face-looking behavior generalize from the lab to the world. AB - Recent laboratory studies have found large, stable individual differences in the location people first fixate when identifying faces, ranging from the brows to the mouth. Importantly, this variation is strongly associated with differences in fixation-specific identification performance such that individuals' recognition ability is maximized when looking at their preferred location (Mehoudar, Arizpe, Baker, & Yovel, 2014; Peterson & Eckstein, 2013). This finding suggests that face representations are retinotopic and individuals enact gaze strategies that optimize identification, yet the extent to which this behavior reflects real world gaze behavior is unknown. Here, we used mobile eye trackers to test whether individual differences in face gaze generalize from lab to real-world vision. In lab fixations were measured with a speeded face identification task, while real world behavior was measured as subjects freely walked around the Massachusetts Institute of Technology campus. We found a strong correlation between the patterns of individual differences in face gaze in the lab and real-world settings. Our findings support the hypothesis that individuals optimize real world face identification by consistently fixating the same location and thus strongly constraining the space of retinotopic input. The methods developed for this study entailed collecting a large set of high-definition, wide field-of-view natural videos from head-mounted cameras and the viewer's fixation position, allowing us to characterize subjects' actually experienced real-world retinotopic images. These images enable us to ask how vision is optimized not just for the statistics of the "natural images" found in web databases, but of the truly natural, retinotopic images that have landed on actual human retinae during real world experience. PMID- 27191942 TI - Motion-based nearest vector metric for reference frame selection in the perception of motion. AB - We investigated how the visual system selects a reference frame for the perception of motion. Two concentric arcs underwent circular motion around the center of the display, where observers fixated. The outer (target) arc's angular velocity profile was modulated by a sine wave midflight whereas the inner (reference) arc moved at a constant angular speed. The task was to report whether the target reversed its direction of motion at any point during its motion. We investigated the effects of spatial and figural factors by systematically varying the radial and angular distances between the arcs, and their relative sizes. We found that the effectiveness of the reference frame decreases with increasing radial- and angular-distance measures. Drastic changes in the relative sizes of the arcs did not influence motion reversal thresholds, suggesting no influence of stimulus form on perceived motion. We also investigated the effect of common velocity by introducing velocity fluctuations to the reference arc as well. We found no effect of whether or not a reference frame has a constant motion. We examined several form- and motion-based metrics, which could potentially unify our findings. We found that a motion-based nearest vector metric can fully account for all the data reported here. These findings suggest that the selection of reference frames for motion processing does not result from a winner-take-all process, but instead, can be explained by a field whose strength decreases with the distance between the nearest motion vectors regardless of the form of the moving objects. PMID- 27191941 TI - Evidence for different processes involved in the effects of nontemporal stimulus size and numerical digit value on duration judgments. AB - Perceived duration has been shown to be positively related to task-irrelevant, nontemporal stimulus magnitude. To account for this finding, Walsh's (2003) A Theory of Magnitude (ATOM) model suggests that magnitude of time is not differentiated from magnitude of other nontemporal stimulus characteristics and collectively processed by a generalized magnitude system. In Experiment 1, we investigated the combined effects of stimulus size and numerical quantity, as two nontemporal stimulus dimensions covered by the ATOM model, on duration judgments. Participants were required to reproduce the duration of target intervals marked by Arabic digits varying in physical size and numerical value. While the effect of stimulus size was effectively moderated by target duration, the effect of numerical value appeared to require attentional resources directed to the numerical value in order to become effective. Experiment 2 was designed to further elucidate the mediating influence of attention on the effect of numerical value on duration judgments. An effect of numerical value was only observed when participants' attention was directed to digit value, but not when participants were required to pay special attention to digit parity. While the ATOM model implies a common metrics and generalized magnitude processing for time, size, and quantity, the present findings provided converging evidence for the notion of two qualitatively different mechanisms underlying the effects of nontemporal stimulus size and numerical value on duration judgments. Furthermore, our data challenge the implicit common assumption that the effect of numerical value on duration judgments represents a continuously increasing function of digit magnitude. PMID- 27191943 TI - Predicting bias in perceived position using attention field models. AB - Attention is the mechanism through which we select relevant information from our visual environment. We have recently demonstrated that attention attracts receptive fields across the visual hierarchy (Klein, Harvey, & Dumoulin, 2014). We captured this receptive field attraction using an attention field model. Here, we apply this model to human perception: We predict that receptive field attraction results in a bias in perceived position, which depends on the size of the underlying receptive fields. We instructed participants to compare the relative position of Gabor stimuli, while we manipulated the focus of attention using exogenous cueing. We varied the eccentric position and spatial frequency of the Gabor stimuli to vary underlying receptive field size. The positional biases as a function of eccentricity matched the predictions by an attention field model, whereas the bias as a function of spatial frequency did not. As spatial frequency and eccentricity are encoded differently across the visual hierarchy, we speculate that they might interact differently with the attention field that is spatially defined. PMID- 27191944 TI - Interaction between contours and eye movements in the perception of afterimages: A test of the signal ambiguity theory. AB - An intriguing property of afterimages is that conscious experience can be strong, weak, or absent following identical stimulus adaptation. Previously we suggested that postadaptation retinal signals are inherently ambiguous, and therefore the perception they evoke is strongly influenced by cues that increase or decrease the likelihood that they represent real objects (the signal ambiguity theory). Here we provide a more definitive test of this theory using two cues previously found to influence afterimage perception in opposite ways and plausibly at separate loci of action. However, by manipulating both cues simultaneously, we found that their effects interacted, consistent with the idea that they affect the same process of object interpretation rather than being independent influences. These findings bring contextual influences on afterimages into more general theories of cue combination, and we suggest that afterimage perception should be considered alongside other areas of vision science where cues are found to interact in their influence on perception. PMID- 27191945 TI - Global shape aftereffects in composite radial frequency patterns. AB - Individual radial frequency (RF) patterns are generated by modulating a circle's radius as a sinusoidal function of polar angle and have been shown to tap into global shape processing mechanisms. Composite RF patterns can reproduce the complex outlines of natural shapes and examining these stimuli may allow us to interrogate global shape mechanisms that are recruited in biologically relevant tasks. We present evidence for a global shape aftereffect in a composite RF pattern stimulus comprising two RF components. Manipulations of the shape, location, size and spatial frequency of the stimuli revealed that this aftereffect could only be explained by the attenuation of intermediate-level global shape mechanisms. The tuning of the aftereffect to test stimulus size also revealed two mechanisms underlying the aftereffect; one that was tuned to size and one that was invariant. Finally, we show that these shape mechanisms may encode some RF information. However, the RF encoding we found was not capable of explaining the full extent of the aftereffect, indicating that encoding of other shape features such as curvature are also important in global shape processing. PMID- 27191948 TI - Cyanoacrylate microbial sealants for skin preparation prior to surgery. AB - BACKGROUND: Surgical site infections (i.e. incisions that become infected) are a continuing concern in health care. Microbial sealant is a liquid that can be applied to the skin immediately before surgery and is thought to help reduce the incidence of surgical site infections (SSIs) by sealing in the skin flora, thus preventing contamination and infection of the surgical site. OBJECTIVES: To assess the effects of the preoperative application of microbial sealants (compared with no microbial sealant) on rates of SSI in people undergoing clean surgery. SEARCH METHODS: For this second update we searched the following electronic databases in May 2015: the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE and EBSCO CINAHL. There were no restrictions based on language or date of publication or study setting. SELECTION CRITERIA: Randomised controlled trials (RCTs) were eligible for inclusion if they involved people undergoing clean surgery (i.e. surgery that does not involve the breathing system, gut, genital or urinary tract, or any part of the body with an existing infection) in an operating theatre and compared the use of preoperative microbial sealants with no microbial sealant. DATA COLLECTION AND ANALYSIS: All review authors independently extracted data on the characteristics, risk of bias and outcomes of the eligible trials. MAIN RESULTS: Seven trials (859 participants undergoing clean surgery) met the inclusion criteria. The trials all compared cyanoacrylate microbial sealant with no sealant. We found there were fewer SSIs with the use of microbial sealant (23/443 participants) than with the control comparison (46/416 participants). There was no evidence of a difference between the two groups in surgical site infection rates following the use of microbial sealants when the results were pooled (risk ratio (RR) 0.53, 95% CI 0.24 to 1.18). There were adverse events in three studies, but these were not judged to be a result of the use of microbial sealant. AUTHORS' CONCLUSIONS: In this second update there is still insufficient evidence available to determine whether the use of microbial sealants reduces the risk of surgical site infection or not. Further rigorous, adequately-powered RCTs are required to investigate this properly. PMID- 27191946 TI - Ultrastable and Biofunctionalizable Gold Nanoparticles. AB - Gold nanoparticles provide an excellent platform for biological and material applications due to their unique physical and chemical properties. However, decreased colloidal stability and formation of irreversible aggregates while freeze-drying nanomaterials limit their use in real world applications. Here, we report a new generation of surface ligands based on a combination of short oligo (ethylene glycol) chains and zwitterions capable of providing nonfouling characteristics while maintaining colloidal stability and functionalization capabilities. Additionally, conjugation of these gold nanoparticles with avidin can help the development of a universal toolkit for further functionalization of nanomaterials. PMID- 27191949 TI - The "New Public" and the "Good Ol' Press": Evaluating Online News Sources During the 2013 Polio Outbreak in Israel. AB - The current research focuses on the 2013 polio outbreak in Israel as a case study to analyze the sources of information used in new media platforms, examining whether the new media have changed the ways in which we communicate about health issues. Specifically, we tracked and coded polio-related references on Hebrew news websites, blogs, forums, and Facebook posts. Overall, 24,388 polio-related references constituted our sampling frame. The findings suggest that there is a moderate-level correlation between the platform and the type of sources chosen by users. Beyond the differences between various platforms, we found that online information platforms rely not only on popular or pseudoscientific sources, but also on high-quality information. In fact, the analysis indicates that online news websites, forums, blogs, and Facebook posts create a unique blend of information, including scientific literature, medical professionals, and government representatives, as well as pseudoscientific research. These findings suggest a more optimistic view of the Internet as a source for health-related information in times of crises. Although the fact that members of the public are exposed to scientific sources does not indicate to what degree this affects their actual decision making. Exposure to a wider variety of sources may enhance health literacy, resulting in a better understanding of information needed to make informed decisions. PMID- 27191947 TI - (1) H MRS in the human spinal cord at 7 T using a dielectric waveguide transmitter, RF shimming and a high density receive array. AB - Multimodal MRI is the state of the art method for clinical diagnostics and therapy monitoring of the spinal cord, with MRS being an emerging modality that has the potential to detect relevant changes of the spinal cord tissue at an earlier stage and to enhance specificity. Methodological challenges related to the small dimensions and deep location of the human spinal cord inside the human body, field fluctuations due to respiratory motion, susceptibility differences to adjacent tissue such as vertebras and pulsatile flow of the cerebrospinal fluid hinder the clinical application of (1) H MRS to the human spinal cord. Complementary to previous studies that partly addressed these problems, this work aims at enhancing the signal-to-noise ratio (SNR) of (1) H MRS in the human spinal cord. To this end a flexible tight fit high density receiver array and ultra-high field strength (7 T) were combined. A dielectric waveguide and dipole antenna transmission coil allowed for dual channel RF shimming, focusing the RF field in the spinal cord, and an inner-volume saturated semi-LASER sequence was used for robust localization in the presence of B1 (+) inhomogeneity. Herein we report the first 7 T spinal cord (1) H MR spectra, which were obtained in seven independent measurements of 128 averages each in three healthy volunteers. The spectra exhibit high quality (full width at half maximum 0.09 ppm, SNR 7.6) and absence of artifacts and allow for reliable quantification of N-acetyl aspartate (NAA) (NAA/Cr (creatine) 1.31 +/- 0.20; Cramer-Rao lower bound (CRLB) 5), total choline containing compounds (Cho) (Cho/Cr 0.32 +/- 0.07; CRLB 7), Cr (CRLB 5) and myo-inositol (mI) (mI/Cr 1.08 +/- 0.22; CRLB 6) in 7.5 min in the human cervical spinal cord. Thus metabolic information from the spinal cord can be obtained in clinically feasible scan times at 7 T, and its benefit for clinical decision making in spinal cord disorders will be investigated in the future using the presented methodology. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27191950 TI - Benchmark Calculations for Bond Dissociation Enthalpies of Unsaturated Methyl Esters and the Bond Dissociation Enthalpies of Methyl Linolenate. AB - It is important to determine an appropriate computational method for obtaining accurate thermochemical properties of large biodiesel molecules such as methyl linolenate. In this study, we use Kohn-Sham density functional theory (DFT) and coupled cluster theory to calculate bond dissociation enthalpies (BDEs) of seven fragment molecules of methyl linolenate, in particular, propene, methyl formate, cis-3-hexene, 1,4-pentadiene, 1-pentene, butane, and methyl butanoate. The results are compared to BDEs obtained from experiments and to Oyeyemi et al.'s multireference averaged coupled pair functional (MRACPF2) calculations. We found that with extrapolation to the complete basis set (CBS) limit, the BDEs derived from coupled cluster calculations with single, double, and triple excitations (CCSDT) and from CCSDT with a perturbative treatment of connected quadruple excitations, CCSDT(2)Q/CBS, are closer to the available experimental values than those obtained by MRACPF2 for propene and methyl formate. The CCSDT/CBS calculations were chosen as the reference for validating the DFT methods. Among the density functionals, we found that M08-HX has the best performance with a mean unsigned deviation (MUD) from CCSDT/CBS of only 1.0 kcal/mol, whereas the much more expensive MRACPF2 has an MUD of 1.1 kcal/mol. We then used the most successfully validated density functionals to calculate the BDEs of methyl linolenate and compared the results with the MRACPF2 BDEs. The present study identifies several Kohn-Sham exchange-correlation functionals that should be useful for modeling ester combustion, especially the M08-HX, M06-2X, M05-2X, M08 SO, and MPWB1K global-hybrid meta functionals, the M11 and MN12-SX range separated-hybrid meta functionals, the omegaB97 range-separated hybrid gradient approximation functional, and the SOGGA11-X global-hybrid gradient approximation functional. PMID- 27191951 TI - Correction: Arabidopsis ERF1 Mediates Cross-Talk between Ethylene and Auxin Biosynthesis during Primary Root Elongation by Regulating ASA1 Expression. AB - [This corrects the article DOI: 10.1371/journal.pgen.1005760.]. PMID- 27191952 TI - Senior Centers and Nutritional Outcomes: A Texas Example. AB - Healthy diet and weight control are important for elders and senior centers (SCs). The authors consider effects of SCs on attendee nutrition and health and efforts to improve diets and weight. Data derive from surveys in 2006 (N = 798) and 2007 (N = 742) at 21 multipurpose SCs in Tarrant County, Texas, supplemented with data from 2012 (N = 1,402). Measures included attendee agreement that SC meals improved nutrition, improved health, attempts to improve diets, and success in controlling weight. Cumulative and binary logistic regression methods were employed. SC attendance and social engagement explained agreement that SC meals improved nutrition and health but were not shown to predict changes in diet or weight control. Findings suggest success of SC programs, as well as physician recommendations, in influencing attendee nutritional behavior and perceptions of nutrition and health effects. Practice recommendations include SC collaborations with local health providers to promote attendee nutritional health. PMID- 27191953 TI - Associations between Screen-Based Sedentary Behaviour and Anxiety Symptoms in Mothers with Young Children. AB - OBJECTIVES: Anxiety is a serious illness and women (including mothers with young children) are at particular risk. Although physical activity (PA) may reduce anxiety risk, little research has investigated the link between sedentary behaviour and anxiety risk. The aim of this study was to examine the association between screen-based sedentary behaviour and anxiety symptoms, independent of PA, amongst mothers with young children. METHODS: During 2013-2014, 528 mothers with children aged 2-5 years completed self-report measures of recreational screen based sedentary behaviour (TV/DVD/video viewing, computer/e-games/hand held device use) and anxiety symptoms (using the Hospital Anxiety and Depression Scale, HADS-A). Linear regression analyses examined the cross-sectional association between screen-based sedentary behaviour and anxiety symptoms. RESULTS: In models that adjusted for key demographic and behavioural covariates (including moderate- to vigorous-intensity PA, MVPA), computer/device use (B = 0.212; 95% CI = 0.048, 0.377) and total screen time (B = 0.109; 95% CI = 0.014, 0.205) were positively associated with heightened anxiety symptoms. TV viewing was not associated with anxiety symptoms in either model. CONCLUSIONS: Higher levels of recreational computer or handheld device use and overall screen time may be linked to higher risk of anxiety symptoms in mothers with young children, independent of MVPA. Further longitudinal and intervention research is required to determine temporal associations. PMID- 27191954 TI - Pemetrexed/Carboplatin/Bevacizumab followed by Maintenance Pemetrexed/Bevacizumab in Hispanic Patients with Non-Squamous Non-Small Cell Lung Cancer: Outcomes according to Thymidylate Synthase Expression. AB - OBJECTIVE: To evaluate the efficacy and safety of pemetrexed, carboplatin and bevacizumab (PCB) followed by maintenance therapy with pemetrexed and bevacizumab (PB) in chemotherapy-naive patients with stage IV non-squamous non-small cell lung cancer (NSCLC) through the influence of thymidylate synthase (TS) protein and mRNA expression on several outcomes. The primary endpoints were the overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). METHODS: A cohort of 144 patients were administered pemetrexed (500 mg/m2), carboplatin (AUC, 5.0 mg/ml/min) and bevacizumab (7.5 mg/kg) intravenously every three weeks for up to four cycles. Maintenance PB was administered until disease progression or unacceptable toxicity. RESULTS: One hundred forty-four Colombian patients with a median follow-up of 13.8 months and a median number of 6 maintenance cycles (range, 1-32) were assessed. The ORR among the patients was 66% (95% CI, 47% to 79%). The median PFS and (OS) rates were 7.9 months (95% CI, 5.9-10.0 months) and 21.4 months (95% CI, 18.3 to 24.4 months), respectively. We documented grade 3/4 hematologic toxicities, including anemia (14%), neutropenia (8%), and thrombocytopenia (16%). The identified grade 3/4 non-hematologic toxicities were proteinuria (2%), venous thrombosis (4%), fatigue (11%), infection (6%), nephrotoxicity (2%), and sensory neuropathy (4%). No grade >3 hemorrhagic events or hypertension cases were reported. OS was significantly higher in patients with the lowest TS mRNA levels [median, 29.6 months (95% CI, 26.2-32.9)] compared with those in patients with higher levels [median, 9.3 months (95% CI, 6.6-12.0); p = 0.0001]. TS expression (mRNA levels or protein expression) did not influence the treatment response. CONCLUSION: Overall, PCB followed by maintenance pemetrexed and bevacizumab was effective and tolerable in Hispanic patients with non-squamous NSCLC. This regimen was associated with acceptable toxicity and prolonged OS, particularly in patients with low TS expression. We found a role for Ki67 and TS expression as prognostic factors. PMID- 27191955 TI - Correction: Decreasing Hepatitis C Virus Infection in Thailand in the Past Decade: Evidence from the 2014 National Survey. AB - [This corrects the article DOI: 10.1371/journal.pone.0149362.]. PMID- 27191956 TI - Correction: Therapist Effects and the Impact of Early Therapeutic Alliance on Symptomatic Outcome in Chronic Fatigue Syndrome. AB - [This corrects the article DOI: 10.1371/journal.pone.0144623.]. PMID- 27191958 TI - Power Asymmetries and Punishment in a Prisoner's Dilemma with Variable Cooperative Investment. AB - In many two-player games, players that invest in punishment finish with lower payoffs than those who abstain from punishing. These results question the effectiveness of punishment at promoting cooperation, especially when retaliation is possible. It has been suggested that these findings may stem from the unrealistic assumption that all players are equal in terms of power. However, a previous empirical study which incorporated power asymmetries into an iterated prisoner's dilemma (IPD) game failed to show that power asymmetries stabilize cooperation when punishment is possible. Instead, players cooperated in response to their partner cooperating, and punishment did not yield any additional increase in tendency to cooperate. Nevertheless, this previous study only allowed an all-or-nothing-rather than a variable-cooperation investment. It is possible that power asymmetries increase the effectiveness of punishment from strong players only when players are able to vary their investment in cooperation. We tested this hypothesis using a modified IPD game which allowed players to vary their investment in cooperation in response to being punished. As in the previous study, punishment from strong players did not increase cooperation under any circumstances. Thus, in two-player games with symmetric strategy sets, punishment does not appear to increase cooperation. PMID- 27191957 TI - Trib2 Suppresses Tumor Initiation in Notch-Driven T-ALL. AB - Trib2 is highly expressed in human T cell acute lymphoblastic leukemia (T-ALL) and is a direct transcriptional target of the oncogenic drivers Notch and TAL1. In human TAL1-driven T-ALL cell lines, Trib2 is proposed to function as an important survival factor, but there is limited information about the role of Trib2 in primary T-ALL. In this study, we investigated the role of Trib2 in the initiation and maintenance of Notch-dependent T-ALL. Trib2 had no effect on the growth and survival of murine T-ALL cell lines in vitro when expression was blocked by shRNAs. To test the function of Trib2 on leukemogenesis in vivo, we generated Trib2 knockout mice. Mice were born at the expected Mendelian frequencies without gross developmental anomalies. Adult mice did not develop pathology or shortened survival, and hematopoiesis, including T cell development, was unperturbed. Using a retroviral model of Notch-induced T-ALL, deletion of Trib2 unexpectedly decreased the latency and increased the penetrance of T-ALL development in vivo. Immunoblotting of primary murine T-ALL cells showed that the absence of Trib2 increased C/EBPalpha expression, a known regulator of cell proliferation, and did not alter AKT or ERK phosphorylation. Although Trib2 was suggested to be highly expressed in T-ALL, transcriptomic analysis of two independent T-ALL cohorts showed that low Trib2 expression correlated with the TLX1-expressing cortical mature T-ALL subtype, whereas high Trib2 expression correlated with the LYL1-expressing early immature T-ALL subtype. These data indicate that Trib2 has a complex role in the pathogenesis of Notch-driven T-ALL, which may vary between different T-ALL subtypes. PMID- 27191959 TI - Emotional Intolerance and Core Features of Anorexia Nervosa: A Dynamic Interaction during Inpatient Treatment? Results from a Longitudinal Diary Study. AB - OBJECTIVE: The role of emotion dysregulation with regard to the psychopathology of anorexia nervosa (AN) is increasingly discussed. It is both assumed that AN symptoms have an impact on difficulties in tolerating aversive emotions and that conversely-emotion dysregulation influences AN. To date, such conclusions are drawn on the basis of cross-sectional data not allowing for inferences on the temporal dynamics. The current study investigates the longitudinal interaction between emotional intolerance and core AN symptoms over the course of inpatient treatment by comparing patients with high (BMI<15 kg/m2) vs. low symptom severity (HSS vs. LSS). METHOD: The study adopted a longitudinal, process-oriented design with N = 16 analysed electronic diaries. Throughout the course of their inpatient treatment, the patients answered questions daily about emotional intolerance and their AN-specific cognitions and behaviours. The temporal dynamics between emotional intolerance and these variables were analysed using a multivariate time series approach. RESULTS: The time series of the processes under investigation adequately reflected the individual treatment courses. The majority of significant linear time trends was found for HSS patients. Most importantly, analysis revealed significant temporal interactions between emotional intolerance and AN symptoms in almost 70% of HSS patients. Thereby, up to 37% of variance in eating restraint and up to 23% in weight concern could be attributed to changes in emotional intolerance. CONCLUSIONS: The findings support the notion that intolerable unpleasant emotions in severely affected AN patients influence their psychopathology. Additionally, time series analysis outlined the inter-individual heterogeneity of psychosomatic treatment courses of AN patients. PMID- 27191960 TI - The Impact of Vision Impairment (IVI) Questionnaire; Validation of the Thai Version and the Implementation on Vision-Related Quality of Life in Thai Rural Community. AB - The objective of this study is to validate the Thai-version of the impact of vision impairment (IVI) questionnaire and to evaluate its impact on vision related quality of life (VRQoL) in southern Thailand. The IVI questionnaire was translated into Thai according to WHO translation guidelines. In addition to the routine ophthalmological examinations, a Thai version of the IVI questionnaire was administered to all participants. A total of 120 patients with visual impairment who presented at Songklanagarind hospital, Songkhla province, were enrolled in the study; 30 had age-related macular degeneration (AMD), 30 had cataract, 30 had diabetic retinopathy, 30 had glaucoma, and 30 non-visually impaired individuals comprised the control group. Statistical analysis demonstrated the Thai-version IVI questionnaire is valid and reliable to evaluate the VRQoL of the Thai patients through three subscales: (i) mobility and independence, (ii) reading and accessing information, and (iii) emotional well being. The results demonstrated high consistency in all subscales with Cronbach's alpha ranging from 0.787 to 0.849. Rasch analysis revealed the validity of the Thai-version IVI to assess VRQoL through all three subscales. Test-retest reliability was also high (intraclass correlation coefficient = 0.96). The composite score of the IVI was significantly higher in participants with visual impairment compared with healthy participants. Moreover, the subscale scores of reading and accessing information, and emotional well-being were highest in participants with AMD. While the subscale scores of mobility and independence were highest among those with either cataracts or diabetic retinopathy. The symptoms of the common vision impairment diseases are associated with an adverse impact on VRQoL in a clinic-based population as demonstrated in this study. PMID- 27191962 TI - Development of proton CT imaging system using plastic scintillator and CCD camera. AB - A proton computed tomography (pCT) imaging system was constructed for evaluation of the error of an x-ray CT (xCT)-to-WEL (water-equivalent length) conversion in treatment planning for proton therapy. In this system, the scintillation light integrated along the beam direction is obtained by photography using the CCD camera, which enables fast and easy data acquisition. The light intensity is converted to the range of the proton beam using a light-to-range conversion table made beforehand, and a pCT image is reconstructed. An experiment for demonstration of the pCT system was performed using a 70 MeV proton beam provided by the AVF930 cyclotron at the National Institute of Radiological Sciences. Three dimensional pCT images were reconstructed from the experimental data. A thin structure of approximately 1 mm was clearly observed, with spatial resolution of pCT images at the same level as that of xCT images. The pCT images of various substances were reconstructed to evaluate the pixel value of pCT images. The image quality was investigated with regard to deterioration including multiple Coulomb scattering. PMID- 27191961 TI - Usual Care and Informed Consent in Clinical Trials of Oxygen Management in Extremely Premature Infants. AB - OBJECTIVE: The adequacy of informed consent in the Surfactant, Positive Pressure, and Pulse Oximetry Randomized Trial (SUPPORT) has been questioned. SUPPORT investigators and publishing editors, heads of government study funding agencies, and many ethicists have argued that informed consent was adequate because the two oxygen saturation target ranges studied fell within a range commonly recommended in guidelines. We sought to determine whether each oxygen target as studied in SUPPORT and four similar randomized controlled trials (RCTs) was consistent with usual care. DESIGN/PARTICIPANTS/SETTING: PubMed, EMBASE, Web of Science, and Scopus were searched for English articles back to 1990 providing information on usual care oxygen management in extremely premature infants. Data were extracted on intended and achieved oxygen saturation levels as determined by pulse oximetry. Twenty-two SUPPORT consent forms were examined for statements about oxygen interventions. RESULTS: While the high oxygen saturation target range (91 to 95%) was consistent with usual care, the low range (85 to 89%) was not used outside of the SUPPORT trial according to surveys and clinical studies of usual care. During usual care, similar lower limits (< 88%) were universally paired with higher upper limits (>= 92%) and providers skewed achieved oxygen saturations toward the upper-end of these intended ranges. Blinded targeting of a low narrow range resulted in significantly lower achieved oxygen saturations and a doubling of time spent below the lower limit of the intended range compared to usual care practices. The SUPPORT consent forms suggested that the low oxygen saturation arm was a widely practiced subset of usual care. CONCLUSIONS: SUPPORT does not exemplify comparative effectiveness research studying practices or therapies in common use. Descriptions of major differences between the interventions studied and commonly practiced usual care, as well as potential risks associated with these differences, are essential elements of adequate informed consent. PMID- 27191963 TI - Chronic Anterior Uveitis in Children. AB - PURPOSE: To describe the visual prognosis and remission rate of chronic anterior uveitis in pediatric patients. METHODS: A retrospective case series of children with chronic anterior uveitis treated in the University of Buenos Aires. Juvenile idiopathic arthritis was defined according to the International League of Associations for Rheumatology criteria. Uveitis remission was defined according to SUN criteria. RESULTS: There were 35 pediatric patients (61 eyes), mean age of uveitis onset was 7.69 +/- 3 years, 60% were females and 74% had bilateral disease, median follow-up was 60 months (range: 12-192 months). JIA was more frequent in females (80.95 vs 21.43; p<0.0001) and oligoarthritis was the most common form. Remission rate was higher in males (HR = 4.99; 95% CI = 1.16-21.51; p = 0.031). More than 40 eyes remained with the same BCVA at 1 year of follow-up. CONCLUSIONS: Although remission was not common and only occurred after long-term follow-up, visual prognosis was good Received 30 August 2015; revised 6 March 2016; accepted 14 March 2016; published online 18 May 2016. PMID- 27191964 TI - Psychological Disorders and Psychosocial Resources of Patients with Newly Diagnosed Bladder and Kidney Cancer: A Cross-Sectional Study. AB - PURPOSE: Psychological disorders have been proven to be associated with poor physiological, psychological and immune outcomes in cancer patients. However, despite of many challenges of the changed self-image/body image and the altered sexual/urinary function, relatively little is known about psychological disorders of patients with newly diagnosed bladder and kidney cancer. We aimed to investigate the prevalence of depression, anxiety, post-traumatic stress disorder (PTSD) and the associated psychosocial factors among bladder/kidney cancer patients. METHODS: A cross-sectional study was conducted of consecutive inpatients with bladder/kidney cancer in the First Affiliated Hospital of China Medical University in Liaoning Province, northeast China. A total of 489 early stage cancer patients eligible for this study completed questionnaires on demographic and clinical variables, depression, anxiety, PTSD, perceived social support and positive psychological variables (hope, optimism and resilience) anonymously during October 2013 and August 2014. Hierarchical regression analysis was used to examine the relationships between psychosocial resources and psychological disorders, while controlling for possible covariates. RESULTS: The prevalence of depression, anxiety and PTSD was 77.5%, 69.3% and 25.2%, respectively, while 24.9% of patients had psychological co-morbidity. Psychosocial resources together explained more than one-third of the variance on psychological disorders. Under standardized estimate (beta) sequence, patient's perception of social support from family was significantly associated with depression, anxiety and PTSD (p < 0.01). Optimism and resilience showed integrated and independent effects on psychological disorders, and hope represented the significant association with PTSD only (p < 0.01). CONCLUSIONS: The high prevalence of psychological disorders in newly diagnosed patients with early-stage bladder/kidney cancer should receive more attention in Chinese medical settings. Additionally, in consideration of the different protective effects of psychosocial resources, the present study demonstrated that one complete psychological intervention integrating the associated psychosocial factors are necessary to ameliorate psychological disorders so as to provide patients with a more holistic cancer care. PMID- 27191965 TI - Folate-Functionalized Magnetic-Mesoporous Silica Nanoparticles for Drug/Gene Codelivery To Potentiate the Antitumor Efficacy. AB - An appropriate codelivery system for chemotherapeutic agents and nucleic acid drugs will provide a more efficacious approach for the treatment of cancer. Combining gene therapy with chemotherapeutics in a single delivery system is more effective than individual delivery systems carrying either gene or drug. In this work, we developed folate (FA) receptor targeted magnetic-mesoporous silica nanoparticles for the codelivery of VEGF shRNA and doxorubicin (DOX) (denoted as M-MSN(DOX)/PEI-FA/VEGF shRNA). Our data showed that M-MSN(DOX)/PEI-FA could strongly condense VEGF shRNA at weight ratios of 30:1, and possesses higher stability against DNase I digestion and sodium heparin. In vitro antitumor activity assays revealed that HeLa cell growth was significantly inhibited. The intracellular accumulation of DOX by confocal microscopy and fluorescence spectrophotometry showed that M-MSN(DOX)/PEI-FA were more easily taken up than nontargeted M-MSN(DOX). Quantitative PCR and ELISA data revealed that M-MSN/PEI FA/VEGF shRNA induced a significant decrease in VEGF expression as compared to cells treated with either the control or other complexes. The invasion and migration phenotypes of the HUVECs were significantly decrease after coculture with MSN/PEI-FA/VEGF shRNA nanocomplexes-treated HeLa cells. The approach provides a potential strategy to treat cancer by a singular nanoparticle delivery system. PMID- 27191966 TI - Prevalence and Correlates of Any and Frequent Synthetic Cannabinoid Use in a Representative Sample of High School Students. AB - BACKGROUND: There is increasing evidence that Synthetic Cannabinoid (SC) use is associated with adverse health effects, but little is known about the prevalence of SC use and risk and protective factors for SC use among adolescents. OBJECTIVES: To determine the prevalence and correlates of any and frequent SC use in a representative sample of high school students. METHODS: The 2013 Youth Risk Behavior Survey was administered to 3,928 high school students in Nevada. A state added question assessed any and frequent SC use (10 or more times). Weighted logistic regression identified factors for both outcomes. RESULTS: 17.3% of students reported SC use and 4.3% used SCs frequently. As expected, there were strong associations between SC use and other substance use. After controlling for substance use, any SC use was associated with being Hispanic (AOR = 1.74; 95% CI = 1.27, 2.38) and living in a rural county (AOR = 1.68; 95% CI = 1.26, 2.23). Frequent SC use was higher among students who were male (AOR = 2.14; 95% CI = 1.19, 3.84), 18 years of age (AOR = 2.34; 95% CI = 1.18, 4.67), lived in a rural county (AOR = 1.84; 95% CI = 1.11, 3.04), and were offered, sold, or given illegal drugs on school property (AOR = 2.40; 95% CI = 1.53, 3.79). Protective factors for frequent SC use included high parental monitoring (AOR = 0.54; 95% CI = 0.31, 0.93) and sports team participation (AOR = 0.61; 95% CI = 0.37, 0.99). CONCLUSIONS/IMPORTANCE: SC prevention policies and programs should focus on adolescents who live in rural settings and engage in substance use. Initiatives to address drug availability as school and promote parent involvement are also warranted. PMID- 27191967 TI - Heterogeneous and Dynamic Prevalence of Asymptomatic Influenza Virus Infections. AB - Influenza infection manifests in a wide spectrum of severity, including symptomless pathogen carriers. We conducted a systematic review and meta-analysis of 55 studies to elucidate the proportional representation of these asymptomatic infected persons. We observed extensive heterogeneity among these studies. The prevalence of asymptomatic carriage (total absence of symptoms) ranged from 5.2% to 35.5% and subclinical cases (illness that did not meet the criteria for acute respiratory or influenza-like illness) from 25.4% to 61.8%. Statistical analysis showed that the heterogeneity could not be explained by the type of influenza, the laboratory tests used to detect the virus, the year of the study, or the location of the study. Projections of infection spread and strategies for disease control require that we identify the proportional representation of these insidious spreaders early on in the emergence of new influenza subtypes or strains and track how this rate evolves over time and space. PMID- 27191969 TI - Do Surgeons or Does Hospital Economics Ultimately Decide Operative Approach? Reply. PMID- 27191970 TI - Infrequent Complications of Inferior Oblique Recession Surgery. AB - PURPOSE: To report the infrequent complications, including antielevation and adherence syndrome, after a unilateral and bilateral inferior oblique (IO) recession procedure and to discuss the possible causes. METHODS: A retrospective chart review was conducted for patients on whom unilateral or bilateral IO weakening surgeries were performed. RESULTS: Forty-three patients were included in the study. In 23 patients unilateral and in 20 patients bilateral IO weakening was performed. All patients underwent IO recession surgery. Mild limitation of elevation developed in two patients and adherence syndrome developed in one patient. All occurred after unilateral IO recession. No duction deficiency was observed in patients after bilateral IO recession. CONCLUSION: Antielevation and adherence syndrome can develop after unilateral IO recession surgery. Care should be taken not to tighten the neurofibrovascular bundle of the IO muscle during surgery. PMID- 27191968 TI - Transcription Factor SP2 Enhanced the Expression of Cd14 in Colitis-Susceptible C3H/HeJBir. AB - Genetic analysis in the IL10-deficient mouse model revealed a modifier locus of experimental inflammatory bowel disease (IBD) on chromosome 18, with the allele of the strain C3H/HeJBir (C3Bir) conferring resistance and the allele of C57BL/6J (B6) conferring susceptibility. Differential Cd14 expression was associated with this background specific susceptibility to intestinal inflammation. Polymorphisms of the Cd14 promoter were found to be likely causative for strain specific expression, and Cd14-knockout mice revealed a protective role of this gene product in experimental IBD. In this study, luciferase reporter assays confirmed an increased activity of the C3Bir derived Cd14 promoter compared to the one of B6. Promoter truncation experiments and site-directed mutagenesis in both strains resulted in reduced Cd14 promoter activity and confirmed that a central AP1 and the proximal SP1 transcription factor binding sites mediated the basal activity of the Cd14 promoter in the mouse. Moreover, a T to C exchange at position -259 replaced putative STAT1 and CDX1 sites in the Cd14 promoter from B6 by a SP2 site in C3Bir. Ablation of the Sp2 site through truncation was associated with a decreased promoter activity. Site-directed mutagenesis also demonstrated that the inactivation of SP2 led to a substantial loss of promoter activity in C3Bir. Performing electrophoretic mobility shift and supershift assays demonstrated interaction of SP2 with its potential binding site. In addition, retroviral mediated overexpression of the SP2 transcription factor in primary bone marrow macrophages derived from C3Bir mice caused a significant increase in Cd14 transcription. These data characterized SP2 as important factor responsible for higher Cd14 expression and reduced IBD susceptibility mediated by the C3Bir allele. PMID- 27191972 TI - Hemophagocytic Lymphohistiocytosis and Progressive Disseminated Histoplasmosis. PMID- 27191971 TI - Selenium reduces enterohemorrhagic Escherichia coli O157:H7 verotoxin production and globotriaosylceramide receptor expression on host cells. AB - AIM: This study investigated the efficacy of selenium (Se) in reducing Escherichia coli O157:H7 verotoxin production and toxin gene expression. Additionally, the effect of Se on globotriaosylceramide (Gb3) receptor in human lymphoma cells was determined. MATERIALS & METHODS: The effect of Se on verotoxin synthesis was determined by standard ELISA, whereas its effect on Gb3 receptor was determined by flow cytometry and real-time quantitative PCR. RESULTS & CONCLUSIONS: Se reduced extracellular and intracellular verotoxin concentration by 40-60% and 80-90%, respectively (p < 0.05), and downregulated verotoxin genes (p < 0.05). Se reduced Gb3 receptor synthesis in lymphoma cells, and real-time quantitative PCR data revealed a significant downregulation of LacCer synthase gene (GalT2) involved in Gb3 synthesis. Further studies are warranted to validate these results in an appropriate animal model. PMID- 27191974 TI - After geneticization. AB - The concept of geneticization belongs to a style of thinking within the social sciences that refers to wide-ranging processes and consequences of genetic knowledge. Lippman's original use of the term was political, anticipating the onerous consequences of genetic reductionism and determinism, while more recent engagements emphasise the productivity and heterogeneity of genetic concepts, practices and technologies. This paper reconstructs the geneticization concept, tracing it back to early political critiques of medicine. The argument is made that geneticization belongs to a style of constructionist thinking that obscures and exaggerates the essentializing effects of genetic knowledge. Following Hacking's advice, we need a more literal sense of construction in terms of 'assembly' to give a clearer account of the relationship between processes and products. Using the 'assemblage' concept to explore the social ontology of genetics, the paper reviews three areas of the empirical literature on geneticization - disease classification, clinical practice and biosociality - to show that a new style of thinking has appeared within the social sciences. In the final assessment, the conditions that gave rise to geneticization are now obsolete. While it may serve as a useful ritual of debate, conceptually geneticization offers a limited account of the heterogeneity of socio-technical change. PMID- 27191973 TI - Bursicon-alpha subunit modulates dLGR2 activity in the adult Drosophila melanogaster midgut independently to Bursicon-beta. AB - Bursicon is the main regulator of post molting and post eclosion processes during arthropod development. The active Bursicon hormone is a heterodimer of Burs-alpha and Burs-beta. However, adult midguts express Burs-alpha to regulate the intestinal stem cell niche. Here, we examined the potential expression and function of its heterodimeric partner, Burs-beta in the adult midgut. Unexpectedly, our evidence suggests that Burs-beta is not significantly expressed in the adult midgut. burs-beta mutants displayed the characteristic developmental defects but showed wild type-like adult midguts, thus uncoupling the developmental and adult phenotypes seen in burs-alpha mutants. Gain of function data and ex vivo experiments using a cAMP biosensor, demonstrated that Burs-alpha is sufficient to drive stem cell quiescence and to activate dLGR2 in the adult midgut. Our evidence suggests that the post developmental transactivation of dLGR2 in the adult midgut is mediated by Burs-alpha and that the beta subunit of Bursicon is dispensable for these activities. PMID- 27191975 TI - Extracellular histones identified in crocodile blood inhibit in-vitro HIV-1 infection. AB - OBJECTIVE: It has been reported that crocodile blood contains potent antibacterial and antiviral properties. However, its effects on HIV-1 infection remain unknown. DESIGN: We obtained blood from saltwater crocodiles to examine whether serum or plasma could inhibit HIV-1 infection. We purified plasma fractions then used liquid chromatography-mass spectrometry to identify the inhibitory protein factor(s). We then analyzed the ability of recombinant proteins to recapitulate HIV-1 inhibition and determine their mechanism of action. METHODS: Crocodylus porosus plasma was tested for inhibition of Jurkat T cell HIV-1 infection. Inhibitor(s) were purified by reverse-phase chromatography then identified by protein liquid chromatography-mass spectrometry. Anti-HIV-1 activity of purified plasma or recombinant proteins were measured by p24 enzyme linked immunosorbent assay and luciferase readouts, and mechanism of action was determined by measuring HIV-1 RNA, cDNA and transcription (using 1G5 cells). RESULTS: Crocodile plasma contains potent inhibitors of HIV-1IIIB infection, which were identified as histones. Recombinant human histones H1 and H2A significantly reduced HIV-1JR-FL infection (IC50 of 0.79 and 0.45 MUmol/l, respectively), whereas H4 enhanced JR-FL luciferase activity. The inhibitory effects of crocodile plasma, recombinant H1 or recombinant H2A on HIV-1 infection were during or post-viral transcription. CONCLUSION: Circulating histones in crocodile blood, possibly released by neutrophil extracellular traps, are significant inhibitors of HIV-1 infection in-vitro. Extracellular recombinant histones have different effects on HIV-1 transcription and protein expression and are downregulated in HIV-1 patients. Circulating histones may be a novel resistance factor during HIV-1 infection, and peptide versions should be explored as future HIV-1 therapeutics that modulate viral transcription. PMID- 27191976 TI - Accelerated CD4+ cell count decline in untreated HIV-1 patients points toward increasing virulence over the course of the epidemic. AB - Based on the assumption that the rate of CD4 cell count loss in treatment-naive patients is correlated with the virulence of HIV-1, we evaluated 4616 patients. Patients who entered a German national database between 1985 and 1995 had a median annual CD4 cell count loss of 48 cells/MUl, whereas those registered between 1999 and 2009 had a median annual CD4 cell count loss of 68 cells/MUl (P < 0.001). This suggests that HIV-1 virulence has increased over the course of the epidemic. PMID- 27191977 TI - Plasma microRNA profiling predicts HIV-associated neurocognitive disorder. AB - OBJECTIVE: HIV-associated neurocognitive disorder (HAND) is a common neurological disorder among HIV-infected patients despite the availability of combination antiretroviral therapy. Host-encoded microRNAs (miRNA) regulate both host and viral gene expression contributing to HAND pathogenesis and can also serve as disease biomarkers. Herein, plasma miRNA profiles were investigated in HIV/AIDS patients with HAND. METHODS: Discovery and Validation Cohorts comprising HIV/AIDS patients were studied that included patients with and without HAND (non-HAND). Plasma miRNA levels were measured by array hybridization and verified by quantitative real-time reverse transcriptase PCR (qRT-PCR). Multiple bioinformatic and biostatistical analyses were applied to the data from each cohort. RESULTS: Expression analyses identified nine miRNAs in the Discovery Cohort (HAND, n = 22; non-HAND, n = 25) with increased levels (>=two-fold) in the HAND group compared with the non-HAND group (P < 0.05). In the Validation Cohort (HAND, n = 12; non-HAND, n = 12) upregulation (>=two-fold) of three miRNAs (miR 3665, miR-4516 and miR-4707-5p) was observed in the HAND group that were also increased in the Discovery Cohort's HAND patients, which were verified subsequently by qRT-PCR. Receiver-operating characteristic curve analyses for the three miRNAs also pointed to the diagnosis of HAND (area under curve, 0.87, P < 0.005). Bioinformatics tools predicted that all three miRNAs targeted sequences of genes implicated in neural development, cell death, inflammation, cell signalling and cytokine functions. CONCLUSION: Differentially expressed plasma derived miRNAs were detected in HIV/AIDS patients with HAND that were conserved across different patient cohorts and laboratory methods. Plasma-derived miRNAs might represent biomarkers for HAND and also provide insights into disease mechanisms. PMID- 27191978 TI - Responsiveness to IL-7 but not to IFN-alpha is diminished in CD4+ T cells from treated HIV infected patients who experience poor CD4+ T-cell recovery. AB - OBJECTIVE: To assess CD4 T-cell responsiveness to IL-7 and IFN-alpha in HIV infected patients who experience poor recovery of CD4 T-cell counts during therapy (immune failure patients). DESIGN: Responses to IL-7 and IFN-alpha were compared between HIV-infected immune failure (CD4 cell counts <379 cells/MUl) patients and immune success (CD4 cell counts >500 cells/MUl) as well as healthy control patients. METHODS: Flow cytometry was used to assess peripheral blood mononuclear cells for IL-7-induced proliferation, CD25 expression, and signaling (signal transducer and activator of transcription 5 phosphorylation and Akt phosphorylation) in CD4 T cells. Freshly isolated cells were characterized by expression of IL-7Ralpha (CD127) among CD4 T-cell maturation subsets by flow cytometry and sorted CD3 T cells were assessed for expression of IFN-alpha and interferon stimulated genes (2'-5'-oligoadenylate synthetase-1 and myxovirus resistance A protein) by quantitative real-time PCR. Responses to IFN-alpha were assessed by induction of signal transducer and activator of transcription 1 phosphorylation and inhibition of IL-7-induced CD4 T-cell proliferation. RESULTS: IL-7-induced proliferation and CD25 expression were decreased in CD4 T cells from immune failure patients. CD127 expressing CD4 T cells were decreased, whereas expression of 2'-5'-oligoadenylate synthetase-1, myxovirus resistance A protein, and IFN-alpha mRNA were increased in total CD3 T cells from immune failure patients. CD127 expression correlated with CD25 induction but not proliferation, whereas T-cell IFN-alpha mRNA was associated with reduced proliferation in CD4 T cells from immune failure patients. IFN-alpha-mediated induction of signal transducer and activator of transcription 1 phosphorylation and inhibition of proliferation were not diminished in CD4 T cells from immune failure patients. CONCLUSION: IL-7 responsiveness is impaired in immune failure patients and may be related to expression of CD127 and IFN-alpha. PMID- 27191979 TI - Association of chronic obstructive pulmonary disease with frailty measurements in HIV-infected and uninfected Veterans. AB - OBJECTIVE: Chronic obstructive pulmonary disease (COPD) prevalence is increasing among aging HIV-infected individuals. We determined the association between COPD and self-reported measures of frailty [adapted frailty-related phenotype (aFRP)] and physical limitation, and a clinical biomarker of physiologic frailty [Veterans Aging Cohort Study (VACS) Index] in HIV-infected compared with uninfected individuals. DESIGN: Cross-sectional study of VACS participants between 2002 and 2012. METHODS: Prefrail/aFRP was obtained from self-reported surveys. Prefrail was defined as 1-2 domains of physical shrinking, exhaustion, slowness and low physical activity; aFRP was defined as at least 3 domains. Physical limitation scale was determined from 12 self-reported survey items assessing limitations performing physical activities. VACS index includes age and laboratory measurements. We used regression models to test for associations between COPD and outcomes in models stratified by HIV status. RESULTS: The sample included 3538 HIV-infected and 3606 uninfected participants; 67 and 63% were black (P = 0.0003), 97 and 92% were men (P < 0.0001) and 4 and 5% had COPD (P = 0.2). In unadjusted analyses, COPD was associated with all three outcomes (P < 0.0001). In adjusted analyses, COPD was associated with increased prefrail and aFRP in HIV-infected and uninfected participants (P <= 0.01 for all comparisons). COPD was associated with physical limitation in both groups (P < 0.0001). There was an interaction between COPD and physical limitation by HIV status with increased physical limitation among HIV-infected participants (P = 0.04). COPD was not associated with VACS index. CONCLUSION: COPD was strongly associated with aFRP and physical limitations. COPD management may mediate frailty through functional limitations rather than physiologic biomarkers, especially in HIV infected individuals. PMID- 27191980 TI - An oxygen-sensitive luminescent Dy(iii) complex. AB - This paper presents the first dysprosium(iii) complex, [{((MeMe)ArO)3tacn}Dy(III)(THF)] (1(Dy)), that shows oxygen-sensitive luminescence. The synthesis, structure and oxygen-sensitive luminescence properties of 1(Dy) are reported (Phi = 0.050 and tau = 17.7 MUs under N2, Phi = 0.011 and tau = 4.1 MUs under O2 and KSV = 305 M(-1) in THF; KSV = 0.0077%(-1) in polystyrene film). The oxygen sensitive mechanism of 1(Dy) is discussed based on the photophysical properties of the corresponding gadolinium(iii) complex, [{((MeMe)ArO)3tacn}Gd(III)(THF)]. PMID- 27191981 TI - Crosstalk between the HIF-1 and Toll-like receptor/nuclear factor-kappaB pathways in the oral squamous cell carcinoma microenvironment. AB - Hypoxia is a prominent feature of the microenvironment of solid tumors and may contribute to tumor progression through the oxygen-sensitive transcriptional regulator hypoxia-inducible factor-1 (HIF-1). Chronic inflammation is another typical feature. Inflammatory mediators, including Toll-like receptors (TLRs) and nuclear factor-kappaB (NF-kappaB), play an important role in cancer development. Recent studies have revealed extensive cross-talk between hypoxia and inflammation signaling, though the mechanisms remain unclear. Our results confirm that TLR3 and TLR4 are highly expressed in oral squamous cell carcinoma (OSCC). Activation of TLR3 and TLR4 stimulated the expression of HIF-1 through NF-kappaB. In addition, HIF-1 increased the expression of TLR3 and TLR4 through direct promoter binding. Thus, the TLR/NF-kappaB pathway forms a positive feedback loop with HIF-1. These results indicate a novel cross-talk between the TLR/NF-kappaB and HIF-1 signaling, which may contribute to OSCC initiation and progression. With the elucidation of this novel mechanism, it might serve as a basis for future microenvironment targeted cancer therapy. PMID- 27191982 TI - The signaling involved in autophagy machinery in keratinocytes and therapeutic approaches for skin diseases. AB - Autophagy is responsible for the lysosomal degradation of proteins, organelles, microorganisms and exogenous particles. Epidermis primarily consists of keratinocytes which functions as an extremely important barrier. Investigation on autophagy in keratinocytes has been continuously renewing, but is not so systematic due to the complexity of the autophagy machinery. Here we reviewed recent studies on the autophagy in keratinocyte with a focus on interplay between autophagy machinery and keratinocytes biology, and novel autophagy regulators identified in keratinocytes. In this review, we discussed the roles of autophagy in apoptosis, differentiation, immune response, survival and melanin metabolism, trying to reveal the possible involvement of autophagy in skin aging, skin disorders and skin color formation. Since autophagy routinely plays a double edged sword role in various conditions, its functions in skin homeostasis and potential application as a therapeutic target for skin diseases remains to be clarified. Furthermore, more investigations are needed on optimizing designed strategies to inhibit or enhance autophagy for clinical efficacy. PMID- 27191985 TI - Gene-expression analysis of gleason grade 3 tumor glands embedded in low- and high-risk prostate cancer. AB - The Gleason score (GS) of prostate cancer on diagnostic biopsies is an important parameter for therapeutic decision-making. Biopsy GS under-estimates the actual GS at radical prostatectomy in a significant number of patients due to samplingartifact. The aim of this study was to identify markers that are differentially expressed in Gleason grade 3 (GG3) tumor glands embedded in GS 4 + 3 = 7 and GS 3 + 3 = 6 prostate cancer using laser capture microdissection and RNA sequencing.GG3 tumor glands embedded in nine GS 3 + 3 = 6 and nine GS 4 + 3 = 7 prostate cancers were isolated by laser capture microdissection of frozen radical prostatectomy specimens. After RNA amplification and RNA sequencing, differentially expressed genes in both GG3 components were identified by a 2log fold change > 1.0 and p-value < 0.05. We applied immunohistochemistry on a tissue micro-array representing 481 radical prostatectomy samples for further validation on protein level.A total of 501 genes were up-regulated and 421 down-regulated in GG3 glands embedded in GS 4 + 3 = 7 as compared to GS 3 + 3 = 6 prostate cancer. We selected HELLS, ZIC2 and ZIC5 genes for further validation. ZIC5 mRNA was up regulated 17 fold (p = 8.4E-07), ZIC2 8 fold (p = 1.3E-05) and HELLS 2 fold (p = 0.006) in GG3 glands derived from GS 4 + 3 = 7. HELLS expression of >= 1% occurred in 10% GS < 7, 17% GS 7 and 43% GS >7 prostate cancer (p < 0.001). Using a cut-off of >= 1%, protein expression of ZIC5 was present in 28% GS < 7, 43% GS 7 and 57% GS > 7 cancer (p < 0.001). ZIC2 was neither associated with GS nor outcome in our validation set. HELLS was independently predictive for biochemical recurrence after radical prostatectomy (HR 2.3; CI 1.5-3.6; p < 0.01).In conclusion, HELLS and ZIC5 might be promising candidate markers for selection of biopsy GS 6 prostate cancer being at risk for up-grading at prostatectomy. PMID- 27191984 TI - Altered methylation of glucosylceramide synthase promoter regulates its expression and associates with acquired multidrug resistance in invasive ductal breast cancer. AB - Overexpression of glucosylceramide synthase (GCS) increases multidrug resistance (MDR) in many cancer cells. However, its mechanism is unknown. The aim of the present study is to detect the association of methylation at the GCS gene promoter with its expression and MDR in invasive ductal breast cancer. 40 cases GCS-positive and 40 cases GCS-negative primary breast carcinoma samples, three drug-sensitive breast cancer cell lines and one multidrug-resistant breast cancer cell line were used. Immunohistochemistry, methylation-specific PCR (MSP), quantitative real-time (qPCR), westernblot and cytotoxicity assay techniques were employed. Thwe results revealed that there was a statistically negative correlation between GCS CpG islands methylation and GCSphenotype in patients with breast cancer. GCS CpG islands methylation was negatively associated with high ER, meanwhile positively with high HER-2 status. Similar results were obtained from the analysis of breast cancer cell lines. Treatment with the demethylating agent 5-aza-2'-deoxycytidine (5-Aza-dc) changed the GCS promoter methylation pattern in three sensitive cells and also caused increased drug resistance of them. These results suggested that the changes of DNA methylation status of the GCS promoter correlates with multidrug resistance in breast cancer. PMID- 27191983 TI - The emerging roles of exosomes in leukemogeneis. AB - Communication between leukemia cells and their environment is essential for the development and progression of leukemia. Exosomes are microvesicles secreted by many types of cells that contain protein and RNA and mediate intercellular communication. The involvement of exosomes has been demonstrated in the crosstalk between leukemic cells, stromal cells and endothelial cells, consequently promoting the survival of leukemic cells, protection of leukemic cells from the cytotoxic effects of chemotherapeutic drugs, angiogenesis and cell migration. At the same time, exosomes can be used for the detection and monitoring of leukemia, with some advantage over current methods of detection and surveillance. As they are involved in immune response towards leukemic cells, exosomes can also potentially be exploited to augment immunotherapy in leukemia. In this review, we first describe the general characteristics of exosomes and biogenesis of exosomes. We then highlight the emerging role of exosomes in different types of leukemia. Finally, the clinical value of exosomes as biomarkers, in vivo drug carriers and novel exosome-based immunotherapy are discussed. PMID- 27191986 TI - GRK3 is a direct target of CREB activation and regulates neuroendocrine differentiation of prostate cancer cells. AB - Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of prostate cancer that commonly arises through neuroendocrine differentiation (NED) of prostate adenocarcinoma (PAC) after therapy, such as radiation therapy and androgen deprivation treatment (ADT). No effective therapeutic is available for NEPC and its molecular mechanisms remain poorly understood. We have reported that G protein-coupled receptor kinase 3 (GRK3, also called ADRBK2) promotes prostate cancer progression. In this study, we demonstrate that the ADT-activated cAMP response element binding protein (CREB) directly targets and induces GRK3. We show GRK3 expression is higher in NEPC than in PAC cells and mouse models, and it positively correlates with the expression and activity of CREB in human prostate cancers. Notably, overexpression of GRK3 in PAC cells increased the expression of NE markers in a kinase activity dependent manner. Conversely, silencing GRK3 blocked CREB-induced NED in PAC cells, reversed NE phenotypes and inhibited proliferation of NEPC cells. Taken together, these results indicate that GRK3 is a new critical activator of NE phenotypes and mediator of CREB activation in promoting NED of prostate cancer cells. PMID- 27191987 TI - Ginsenoside Rg1 and platelet-rich fibrin enhance human breast adipose-derived stem cell function for soft tissue regeneration. AB - Adipose-derived stem cells (ASCs) can be used to repair soft tissue defects, wounds, burns, and scars and to regenerate various damaged tissues. The cell differentiation capacity of ASCs is crucial for engineered adipose tissue regeneration in reconstructive and plastic surgery. We previously reported that ginsenoside Rg1 (G-Rg1 or Rg1) promotes proliferation and differentiation of ASCs in vitro and in vivio. Here we show that both G-Rg1 and platelet-rich fibrin (PRF) improve the proliferation, differentiation, and soft tissue regeneration capacity of human breast adipose-derived stem cells (HBASCs) on collagen type I sponge scaffolds in vitro and in vivo. Three months after transplantation, tissue wet weight, adipocyte number, intracellular lipid, microvessel density, and gene and protein expression of VEGF, HIF-1alpha, and PPARgamma were higher in both G Rg1- and PRF-treated HBASCs than in control grafts. More extensive new adipose tissue formation was evident after treatment with G-Rg1 or PRF. In summary, G-Rg1 and/or PRF co-administration improves the function of HBASCs for soft tissue regeneration engineering. PMID- 27191988 TI - Elevated ZC3H15 increases HCC growth and predicts poor survival after surgical resection. AB - Zinc finger CCCH-type containing 15 (ZC3H15), also known as DRG family regulatory protein 1 (DFRP1), is a highly conserved eukaryotic protein that associates with active translation machinery. The aim of our study was to explore the clinical relevance and intrinsic functions of ZC3H15 in hepatocellular carcinoma (HCC). We constructed a cohort with 261 tumor and matched normal tissues from HCC patients. ZC3H15 protein and mRNA levels were determined using immunohistochemistry, western blot analysis, and quantitative polymerase chain reaction. ZC3H15 was highly expressed in the majority of HCC cases, and high ZC3H15 levels were significantly associated with high serum a-fetoprotein (AFP) levels (>20 ng/mL) and vascular invasion. Kaplan-Meier and Cox regression data indicated that elevated ZC3H15 was an independent predictor for HCC-specific disease-free survival (hazards ratio [HR], 1.789; 95% confidence interval [95% CI], 1.298 2.466 [P=0.0004]) and overall survival (HR, 1.613; 95% CI, 1.120-2.322 [P=0.0101]). Interaction of ZC3H15 with TRAF2 increased activation of NFkappaB signaling. These results suggest ZC3H15 is an independent prognostic marker in HCC patients that is clinicopathologically associated with tumor invasion and serum AFP levels. PMID- 27191990 TI - A unique set of 6 circulating microRNAs for early detection of non-small cell lung cancer. AB - INTRODUCTION: Circulating microRNAs are promising biomarkers for diagnosis, predication and prognostication of diseases. Lung cancer is the cancer disease accountable for most cancer deaths, largely due to being diagnosed at late stages. Therefore, diagnosing lung cancer patients at an early stage is crucial for improving the outcome. The purpose of this study was to identify circulating microRNAs for detection of early stage lung cancer, capable of discriminating lung cancer patients from those with chronic obstructive pulmonary disease (COPD) and healthy volunteers. RESULTS: We identified 7 microRNAs separating lung cancer patients from controls. By using RT-qPCR, we validated 6 microRNAs (miR-429, miR 205, miR-200b, miR-203, miR-125b and miR-34b) with a significantly higher abundance in serum from NSCLC patients. Furthermore, the 6 miRNAs were validated in a different dataset, revealing an area under the receiver operating characteristic curve of 0.89 for stage I-IV and 0.88 for stage I/II. MATERIALS AND METHODS: We profiled the expression of 754 unique microRNAs by TaqMan Low Density Arrays, and analyzed serum from 38 patients with NSCLC, 16 patients suffering from COPD and 16 healthy volunteers from Norway, to explore their potential as diagnostic biomarkers. For validation, we analyzed serum collected from high-risk individuals enrolled in the Valencia branch of the International Early Lung Cancer Action Program screening trial (n=107) in addition to 51 lung cancer patients. CONCLUSIONS: Considering the accessibility and stability of circulating miRNAs, these 6 microRNAs are promising biomarkers as a supplement in future screening studies. PMID- 27191991 TI - Pathological complete response as a surrogate for relapse-free survival in patients with triple negative breast cancer after neoadjuvant chemotherapy. AB - We retrospective analyzed triple negative breast cancer (TNBC) patients who received either taxane-based or anthracycline-based neoadjuvant chemotherapy, evaluated whether pathological complete response (pCR) is a surrogate endpoint for relapse free survival (RFS) in TNBC and explored which subgroup of patients benefits more from superior treatment regimen. 186 patients received taxane-based (Group A) or anthracycline-based (Group B) neoadjuvant chemotherapy, median follow-up was 48.1 months. 42 patients received total pCR (ypT0/is ypN0), 34 in Group A and 8 in Group B, p < 0.001. Patients who achieved pCR had an increased RFS when compared with non-pCR patients, p = 0.043. Patients in Group A had a better RFS, p = 0.025, after adjusting for tumor size and clinical lymph node status before neoadjuvant therapy. Only patients sensitive to neoadjuvant chemotherapy exhibited RFS benefit from taxane-based treatment, and those who were treatment insensitive had similar RFS between both groups. Our analysis showed Taxane-based regimen had higher pCR rate and could predict improved RFS in TNBC, and the prognostic value was greater in treatment sensitive patients. This retrospective analysis supports the use of pCR as a surrogate endpoint for RFS in TNBC. PMID- 27191989 TI - Proteomic analysis of stromal proteins in different stages of colorectal cancer establishes Tenascin-C as a stromal biomarker for colorectal cancer metastasis. AB - Tumor microenvironment is crucial to tumor development and metastasis. Little is known about the roles of stromal proteins in colorectal carcinogenesis. In this study, we used a combination of laser capture microdissection (LCM), iTRAQ labeling and two-dimensional liquid chromatography-tandem mass spectrometry (2D LC-MS/MS) to compare stromal proteomes in different stages of colorectal cancer. A total of 1966 proteins were identified, and 222 proteins presenting a significant fold change were quantified in different stages. Differentially expressed proteins (DEPs) were subjected to cluster and pathway analyses. We confirmed the differential expression of Tenascin-C and S100A9 using immunohistochemical analysis, and found that the expression levels of S100A9 and Tenascin-C were correlated with TNM stages and metastasis. In addition, our results showed that Tenascin-C was abundantly secreted by the colon cancer cells with high metastatic potential, and highly expressed in lymph nodes with metastasis. Our studies not only shed light on the mechanism by which stromal proteins contributed to colorectal carcinogenesis, but also identified Tenascin-C as a potential stromal biomarker for colorectal cancer metastasis. PMID- 27191994 TI - Methylation-mediated repression of microRNA-129-2 suppresses cell aggressiveness by inhibiting high mobility group box 1 in human hepatocellular carcinoma. AB - Aberrant expression of microRNAs (miRNAs) and its dysfunction have been revealed as crucial modulators of cancer initiation and progression. MiR-129-2 has been reported to play a tumor suppressive role in different human malignancies. Here, we demonstrated that miR-129-2 was significantly decreased in hepatocellular carcinoma (HCC) tissues and cell lines. Furthermore, miR-129-2 was expressed at significant lower levels in aggressive and recurrent tumor tissues. Clinical analysis indicated that miR-129-2 expression was inversely correlated with venous infiltration, high Edmondson-Steiner grading and advanced tumor-node-metastasis (TNM) stage in HCC. Notably, miR-129-2 was an independent prognostic factor for indicating overall survival (OS) and disease-free survival (DFS) of HCC patients. Ectopic expression of miR-129-2 inhibited cell migration and invasion in vitro and in vivo. Furthermore, we confirmed that high mobility group box 1 (HMGB1) was a direct target of miR-129-2, and it abrogated the function of miR-129-2 in HCC. Mechanistic investigations showed that miR-129-2 overexpression inhibited AKT phosphorylation at Ser473 and decreased the expression of matrix metalloproteinase2/9 (MMP2/9). Upregulation of p-AKT abolished the decreased cell migration and invasion induced by miR-129-2 in HCC. Whereas inhibition of Akt phosphorylation significantly decreased HMGB1-enhanced HCC cell migration and invasion. Moreover, we found that miR-129-2 was downregulated by DNA methylation, and demethylation of miR-129-2 increased miR-129-2 expression in HCC cells and resulted in significant inhibitory effects on cell migration and invasion. In conclusion, miR-129-2 may serve as a prognostic indicator for HCC patients and exerts tumor suppressive role, at least in part, by inhibiting HMGB1. PMID- 27191993 TI - The histone methyltransferase EZH2 as a novel prosurvival factor in clinically aggressive chronic lymphocytic leukemia. AB - The histone methyltransferase EZH2 induces gene repression through trimethylation of histone H3 at lysine 27 (H3K27me3). EZH2 overexpression has been reported in many types of cancer and associated with poor prognosis. Here we investigated the expression and functionality of EZH2 in chronic lymphocytic leukemia (CLL). Aggressive cases with unmutated IGHV genes (U-CLL) displayed significantly higher EZH2 expression compared to indolent CLL cases with mutated IGHV genes (M-CLL); furthermore, in U-CLL EZH2 expression was upregulated with disease progression. Within U-CLL, EZH2high cases harbored significantly fewer (p = 0.033) TP53 gene abnormalities compared to EZH2low cases. EZH2high cases displayed high H3K27me3 levels and increased viability suggesting that EZH2 is functional and likely confers a survival advantage to CLL cells. This argument was further supported by siRNA-mediated downmodulation of EZH2 which resulted in increased apoptosis. Notably, at the intraclonal level, cell proliferation was significantly associated with EZH2 expression. Treatment of primary CLL cells with EZH2 inhibitors induced downregulation of H3K27me3 levels leading to increased cell apoptosis. In conclusion, EZH2 is overexpressed in adverse-prognosis CLL and associated with increased cell survival and proliferation. Pharmacologic inhibition of EZH2 catalytic activity promotes apoptosis, highlighting EZH2 as a novel potential therapeutic target for specific subgroups of patients with CLL. PMID- 27191996 TI - Programmed death-ligand-1 expression in advanced gastric cancer detected with RNA in situ hybridization and its clinical significance. AB - PD-L1 expression may be a predictive marker for anti-PD-1 therapeutic efficacy. No standard detection method of PD-L1 expression was available for advanced gastric cancer (AGC), which would be investigated in this study using RNA in situ hybridization and immunohistochemistry. Patients (N = 165) with AGC treated at Peking University Cancer Hospital from October 2008 to February 2013 were retrospectively studied. Tissue samples prior to chemotherapy were assessed for PD-L1 expression using RNA in situ hybridization (an RNAscope assay) and immunohistochemistry (IHC). The correlations of PD-L1 expression to patient characteristics and clinical outcomes were statistically analyzed. PD-L1 mRNA signals were located in tumor compartments or the mesenchyme in a brown dotted or clustered pattern, and PD-L1 mRNA expression in gastric cancer was heterogeneous. PD-L1-positive expressions were observed in 33.9% (56/165) and 35.1% (46/131) patients in mRNA level and protein level, respectively. A positive relationship was found between PD-L1 mRNA and PD-L1 protein, and compared to IHC, RNAscope assay could provide an intuitional and quantitative data with potential clinical application. No statistically significant differences occurred between PD-L1 expression and clinical response to chemotherapy, or survival. However, we found that PD-L1 expression was higher in intestinal type than in diffuse type. These findings suggested that the RNAscope assay may be a promising method for patient assessment in gastric cancer clinical trials, which would be illustrated in further study. PMID- 27191992 TI - Practical aspects of NGS-based pathways analysis for personalized cancer science and medicine. AB - Nowadays, the personalized approach to health care and cancer care in particular is becoming more and more popular and is taking an important place in the translational medicine paradigm. In some cases, detection of the patient-specific individual mutations that point to a targeted therapy has already become a routine practice for clinical oncologists. Wider panels of genetic markers are also on the market which cover a greater number of possible oncogenes including those with lower reliability of resulting medical conclusions. In light of the large availability of high-throughput technologies, it is very tempting to use complete patient-specific New Generation Sequencing (NGS) or other "omics" data for cancer treatment guidance. However, there are still no gold standard methods and protocols to evaluate them. Here we will discuss the clinical utility of each of the data types and describe a systems biology approach adapted for single patient measurements. We will try to summarize the current state of the field focusing on the clinically relevant case-studies and practical aspects of data processing. PMID- 27191998 TI - Can new treatment developments combat resistance in malaria? PMID- 27191995 TI - Strategies to improve treatment outcome in gastric cancer: a retrospective analysis of patients from two high-volume hospitals in Korea and China. AB - China has high incidence of gastric cancer (GC). However, the treatment outcomes of China were unsatisfactory compared to those of Korea. We performed this study to compare tumour characteristics, treatment parameters, and survival outcomes of GC patients between Korea and China based on the databases of two high-volume hospitals, with the aim of identifying indicators of GC prognosis. Data of patients undergoing gastrectomy for GC from 2006 to 2010 were analysed retrospectively. Subgroup survival analyses, stratified by clinicopathologic factors and multivariable analyses, were performed. The interactive roles of chemotherapy and D2 lymphadenectomy for overall survival were also investigated. Among 1365 Chinese and 4981 Korean patients, the proportion of early cancer detection in Chinese patients was much lower relative to that of Korean patients. There were no significant differences between countries in terms of surgical morbidity and mortality. The overall 5-year survival rates were 54.3% and 81.4%; when stratified by clinicopathologic factors, the survival were generally statistically higher in Korean patients. Gender, age, T stage, N stage, extent of lymphadenectomy, radicality of surgery, resection type, and chemotherapy were independently associated with survival in patients without metastasis. Survival rates for stage II and III GC differed significantly between the two countries, but this difference was eliminated among patients who underwent D2 lymphadenectomy or received chemotherapy. These treatments were given to patients with advanced-stage diagnoses (approximately 20% and 80% of patients, respectively). Treatment type was selected as independent prognostic factors in stage I-III and D2/D2+, with chemotherapy resulting in the best prognosis. Many differences in GC tumour characteristics exist between two countries. Early cancer detection and standardized treatment in Korea contribute to superior survival rates. Promotion of an early screening program, training and dissemination of standard D2 lymphadenectomy, and appropriate applications of chemotherapy would improve survival outcomes. PMID- 27192006 TI - Doctor to Doctor. PMID- 27192005 TI - Get a Medical Student. PMID- 27192007 TI - The Medical Bookshelf. PMID- 27191997 TI - A novel microfluidic model can mimic organ-specific metastasis of circulating tumor cells. AB - A biomimetic microsystem might compensate costly and time-consuming animal metastatic models. Herein we developed a biomimetic microfluidic model to study cancer metastasis. Primary cells isolated from different organs were cultured on the microlfuidic model to represent individual organs. Breast and salivary gland cancer cells were driven to flow over primary cell culture chambers, mimicking dynamic adhesion of circulating tumor cells (CTCs) to endothelium in vivo. These flowing artificial CTCs showed different metastatic potentials to lung on the microfluidic model. The traditional nude mouse model of lung metastasis was performed to investigate the physiological similarity of the microfluidic model to animal models. It was found that the metastatic potential of different cancer cells assessed by the microfluidic model was in agreement with that assessed by the nude mouse model. Furthermore, it was demonstrated that the metastatic inhibitor AMD3100 inhibited lung metastasis effectively in both the microfluidic model and the nude mouse model. Then the microfluidic model was used to mimick liver and bone metastasis of CTCs and confirm the potential for research of multiple-organ metastasis. Thus, the metastasis of CTCs to different organs was reconstituted on the microfluidic model. It may expand the capabilities of traditional cell culture models, providing a low-cost, time-saving, and rapid alternative to animal models. PMID- 27192009 TI - A special prescription for Mrs Rowbottom. PMID- 27192008 TI - Bowel disorders. PMID- 27192010 TI - Cme Credit QUIZ. PMID- 27192011 TI - Primary Care Digest. PMID- 27192013 TI - Diverticular Disease. PMID- 27192014 TI - Acyl-homoserine Lactone from Saccharum * officinarum with Stereochemistry Dependent Growth Regulatory Activity. AB - Acyl-homoserine lactones (AHLs) are a class of compounds produced by Gram negative bacteria that are used in a process of chemical communication called quorum sensing. Much is known about how bacteria use these chemical compounds to control the expression of important factors; however, there have been few reports about the presence and effects of AHLs in plants. In this study, the phytochemical study of leaves and culms of sugar cane (Saccharum * officinarum) led to the identification of N-(3-oxo-octanoyl)homoserine lactone. Since the absolute configuration of the natural product could not be determined, both R and S enantiomers of N-(3-oxo-octanoyl)homoserine lactone were synthesized and tested in sugar cane culms. The enantiomers caused changes in the mass and length of buds and roots when used at micromolar concentrations. Using the sugar cane RB96 6928 variety, the S enantiomer increased sprouting of roots more effectively than the R enantiomer. Furthermore, scanning electron microscopy showed that both the R and S enantiomers led to more stretched root cells compared with the control. PMID- 27192015 TI - Active insecticides for Diaphania hyalinata selective for the natural enemy Solenopsis saevissima. AB - The objective of this study was to determine the toxicity of the nine synthetic dienamides against the insect pest Diaphania hyalinata (melonworm) and the selectivity of these substances for the predator Solenopsis saevissima (fire ant). Four bioassays were conducted. To begin with, the dienamides that caused high mortality of D. hyalinata have been selected. In the second bioassay the dose-mortality curves of the selected dienamides have been constructed. In the third bioassay, the survival curves for D. hyalinata and the elapsed time to kill 50% of their population have been determined. In the fourth biological test, the selectivity of the substances to the predator S. saevissima has been evaluated. The most active (2E,4E)-N-butylhexa-2,4-dienamide 3d has killed 95% of the melonworm, D. hyalinata, and less than 10% of the natural enemy S. saevissima. The results presented by this compound are superior to the outcome displayed by the commercial insecticide Malathion(r). Three of the dienamides prepared in this manuscript have proven to be selective in killing the pest, but not the beneficial insect. PMID- 27192017 TI - Comparative Molecular Dynamics Study on Tri-n-butyl Phosphate in Organic and Aqueous Environments and Its Relevance to Nuclear Extraction Processes. AB - A refined model for tri-n-butyl phosphate (TBP), which uses a new set of partial charges generated from our ab initio density functional theory calculations, has been proposed in this study. Molecular dynamics simulations are conducted to determine the thermodynamic properties, transport properties, and the microscopic structures of liquid TBP, TBP/water mixtures, and TBP/n-alkane mixtures. These results are compared with those obtained from four other TBP models, previously described in the literature. We conclude that our refined TBP model appears to be the only TBP model from this set that, with reasonable accuracy, can simultaneously predict the properties of TBP in bulk TBP, in organic diluents, and in aqueous solution. The other models only work well for two of the three systems mentioned above. This new TBP model is thus appropriate for the simulation of liquid-liquid extraction systems in the nuclear extraction process, where one needs to simultaneously model TBP in both aqueous and organic phases. It is also promising for the investigation of the microscopic structure of the organic phase in these processes and for the characterization of third-phase formation, where TBP again interacts simultaneously with both polar and nonpolar molecules. Because the proposed TBP model uses OPLS-2005 Lennard-Jones parameters, it may be used with confidence to model mixtures of TBP with other species whose parameters are given by the OPLS-2005 force field. PMID- 27192016 TI - Circulating microRNAs predict future fatal myocardial infarction in healthy individuals - The HUNT study. AB - Coronary heart disease is the most common cause of death, and the number of individuals at risk is increasing. To better manage this pandemic, improved tool for risk prediction, including more accurate biomarkers are needed. The objective of this study was to assess the utility of circulating microRNAs (miRs) to predict future fatal acute myocardial infarction (AMI) in healthy participants. We performed a prospective nested case-control study with 10-year observation period and fatal AMI as endpoint. In total, 179 miRs were quantified by real-time polymerase chain reaction in serum of 112 healthy participants (40-70years) that either (1) suffered from fatal AMI within 10years [n=56], or (2) remained healthy [n=56, risk factor-matched controls]. Candidate miRs were validated in a separate cohort of healthy individuals (n=100). Twelve miRs were differently expressed in cases and controls in the derivation cohort (p<0.05). Among these, 10 miRs differed significantly between cases and controls in the validation cohort (p<0.05). We identified gender dimorphisms, as miR-424-5p and miR-26a-5p were associated exclusively with risk in men and women, respectively. The best model for predicting future AMI consisted of miR-106a-5p, miR-424-5p, let-7g-5p, miR 144-3p and miR-660-5p, providing 77.6% correct classification for both genders, and 74.1% and 81.8% for men and women, respectively. Adding these 5 miRs to the Framingham Risk Score, increased the AUC from 0.72 to 0.91 (p<0.001). In conclusion, we identified several miRs associated with future AMI, revealed gender-specific associations, and proposed a panel of 5 miRs to enhance AMI risk prediction in healthy individuals. PMID- 27192018 TI - Self-assembly of polymeric micelles into complex but regular superstructures based on highly controllable core-core fusion between the micelles. AB - Herein, we report a facile but highly controllable method to induce core-core fusion for not only spherical but also worm-like polymeric micelles, leading to various complex but regular superstructures including "random worm-like co micelles", "block worm-like co-micelles" and octopus-like superparticles. PMID- 27192019 TI - AFM Studies on Liquid Superlubricity between Silica Surfaces Achieved with Surfactant Micelles. AB - By using atomic force microscopy (AFM), we showed that the liquid superlubricity with a superlow friction coefficient of 0.0007 can be achieved between two silica surfaces lubricated by hexadecyltrimethylammonium bromide (C16TAB) solution. There exists a critical load that the lubrication state translates from superlow friction to high friction reversibly. To analyze the superlow friction mechanism and the factors influencing the critical load, we used AFM to measure the structure of adsorbed C16TAB molecules and the normal force between two silica surfaces. Experimental results indicate that the C16TAB molecules are firmly adsorbed on the two silica surfaces by electrostatic interaction, forming cylinder-like micelles. Meanwhile, the positively charged headgroups exposed to solution produce the hydration and double layer repulsion to bear the applied load. By controlling the concentration of C16TAB solution, it is confirmed that the critical load of superlow friction is determined by the maximal normal force produced by the hydration layer. Finally, the superlow friction mechanism was proposed that the adsorbed micellar layer forms the hydration layer, making the two friction surfaces be in the repulsive region and meanwhile providing excellent fluidity without adhesion between micelles. PMID- 27192020 TI - Neutrophil-related and serum biomarkers in granulomatosis with polyangiitis support extracellular traps mechanism of the disease. AB - OBJECTIVES: Granulomatosis with polyangiitis (GPA) is an autoimmune disease with still unknown etiology. Recent studies indicate that neutrophils extra-cellular traps participate in the pathophysiology of GPA. This study investigates the levels of circulating NET formation markers and neutrophil-platelet interaction in patients with GPA. METHODS: We enrolled 40 GPA patients (20 in the active stage of the disease and 20 in remission). Twenty sex- and age-matched healthy subjects served as a control group. Serum/plasma levels of serine proteases, and histone-, myeloperoxidase-, proteinase-3 DNA complexes and sP-selectin were measured using ELISA or Luminex assays. Circulating platelet-neutrophil aggregates and neutrophils activation markers expression was measured by flow cytometry. RESULTS: Patients in active stage of GPA had higher circulating levels of serine proteases, DNA-histone and myeloperoxidase -DNA complexes. In addition, platelet-neutrophil aggregates and sP-selectin were also elevated in this group. Platelet-neutrophil aggregates and myeloperoxidase -DNA complexes correlated positively with the disease activity score (BVAS). CONCLUSIONS: NETs production and activation of platelets in GPA is supported by elevated myeloperoxidase-DNA complexes and platelet-neutrophil aggregates correlating positively with the disease activity score. This mechanism justifies laboratory measurements of myeloperoxidase-DNA complexes and plasma sP-selectin as biomarkers for studying GPA activity. PMID- 27192021 TI - Chiral Sensor for Enantiodiscrimination of Varied Acids. AB - A chiral thiophosphoroamide 4 derived from (1R,2R)-1,2-diaminocyclohexane is used as a highly effective chiral sensor for the chiral recognition of varied acids via ion-pairing and hydrogen-bonding interactions using (1)H, (19)F and (31)P NMR. PMID- 27192022 TI - A system for evaluating the impact of noise pollution on the population's health. AB - The aim of this study was to develop a support system for the evaluation of noise pollution, applied to the central urban area of Rio Claro, Sao Paulo State, Brazil. Data were obtained from noise measurements and interviews with the population, generating the following indicators: equivalent sound level (Leq ), traffic noise index (LTNI ), and a participatory diagnosis (Dp ), integrated through a fuzzy inference system (FIS). The proposed system allowed classifying the measurement points according to the degree of impact of noise pollution on the population's health (IPS ) in the study area. Impact was considered significant in 31.4% of the measurement points and very significant in 62.9%. The FIS can be adjusted to local conditions, allowing generalization and thus also supporting noise pollution evaluation and respective environmental noise management in other geographic areas. PMID- 27192023 TI - In the choice between health and money, health comes first: an analysis of happiness among rural Chilean elderly. AB - We studied the relationship between happiness and individual socio-demographic context and health and dietary variables by interviewing 389 elderly individuals (age 60-90 years) living in rural areas in the Maule Region of Central Chile. The Lyubomirsky & Lepper (1999) subjective happiness scale was used. Ordinal logistic regression models were estimated. The discrete dependent variable was level of happiness. The following variables were significantly associated with happiness: (1) individual socio-demographic variables like age and satisfaction with the economic situation; (2) health variables like independence in activities of daily living, common activities, and self-rated health; and (3) dietary variables such as life satisfaction related to food and the frequency with which the elders shared dinner with others. The study results suggest more efficient efforts at healthy eating for the elderly in rural areas. PMID- 27192024 TI - Zika virus and women. PMID- 27192025 TI - Eating patterns in the Brazilian Longitudinal Study of Adult Health (ELSA Brasil): an exploratory analysis. AB - The food consumption of 15,071 public employees was analyzed in six Brazilian cities participating in the baseline for Brazilian Longitudinal Study of Adult Health (ELSA-Brasil, 2008-2010) with the aim of identifying eating patterns and their relationship to socio-demographic variables. Multiple correspondence and cluster analysis were applied. Four patterns were identified, with their respective frequencies: "traditional" (48%); "fruits and vegetables" (25%); "pastry shop" (24%); and "diet/light" (5%) The "traditional" and "pastry shop" patterns were more frequent among men, younger individuals, and those with less schooling. "Fruits and vegetables" and "diet/light" were more frequent in women, older individuals, and those with more schooling. Our findings show the inclusion of new items in the "traditional" pattern and the appearance of the "low sugar/low fat" pattern among the eating habits of Brazilian workers, and signal socio-demographic and regional differences. PMID- 27192026 TI - The debate on abortion and Zika: lessons from the AIDS epidemic. PMID- 27192027 TI - [A comprehensive and critical view of conceptual models for access to health services, 1970-2013]. AB - The aim of this study was to critically analyze various conceptual models on access to health services described in the literature from 1970 to 2013. A systematic review was conducted on applied and theoretical research publications that explicitly conceptualized access to health services. The review included 25 articles that met the study's objectives. The analysis used a matrix containing the conceptual model's logic and its description. Access to health services was classified in five categories: (i) decent minimums, (ii) market-driven, (iii) factors and multicausality, (iv) needs-based, and (v) social justice and the right to health. The study concludes that the predominant concept of access in the literature has been the market logic of medical care services, linked to the logic of factors and multicausality. Meanwhile, no conceptual model was found for access to health services based explicitly on social justice and the right to health. PMID- 27192028 TI - Is cognitive decline in the elderly associated with contextual income? Results of a population-based study in southern Brazil. AB - The aim of this study was to estimate the association between contextual income and cognitive decline in the elderly in Florianopolis, a medium-sized city in southern Brazil. A nested cross-sectional study was performed in a cohort of elderly >= 60 years (n = 1,197), interviewed in the second wave (2013/2014) of the EpiFloripa cohort. Cognitive decline was assessed with the Mini Mental State Examination (MMSE) and contextual income was measured as the mean monthly income of the heads of households. Individual adjustment variables were sex, age, skin color, per capita household income, years of schooling, and time living in the neighborhood. The data were analyzed using multilevel logistic regression. The odds of cognitive decline were twice as high (OR = 1.99; 95%CI: 1.03; 3.87) in elderly living in census tracts with the lowest income quintile compared to those in the highest quintile, independently of individual characteristics. In conclusion, the socioeconomic environment is related to cognitive decline and should be considered in public policies with a focus on health of the elderly. PMID- 27192029 TI - [Where Descartes got it right: the implications for science, biomedicine, and public health]. AB - The "received view" of Descartes has shaped the image of a dualist thinker who radically separated mind and body and thus laid the foundations for a "divided modernity". Numerous epithets have been applied to Cartesian thinking, all of which now sound depreciative: mechanicism, determinism, and reductionism, among others. This article contends that Descartes was not the type of dualist that is normally assumed. Based on a rereading of two essential works (Discourse on Method and Metaphysical Meditations) and a dialogue with the new literature on the theme, we contend that overcoming the "received view" of Descartes can shed new light on discussions in (and of) the collective health field and highlight the so-called expanded health paradigm (including aspects beyond the biological or physiological, such as the psychological, social, economic, cultural, and political). PMID- 27192031 TI - Zika in Cadernos de Saude Publica / Reports in Public Health: again? PMID- 27192032 TI - Barriers and Facilitators to the Use of Mental Health Services by Women With Elevated Symptoms of Depression and Their Partners. AB - This qualitative descriptive study explored the barriers and facilitators to the use of mental health services reported by women with elevated symptoms of depression in the postpartum period and their partners. Data were collected through individual semi-structured interviews of 30 heterosexual couples. Content analysis revealed five principal barriers and facilitators: (a) accessibility and proximity, (b) appropriateness and fit, (d) stigma, (e) encouraged to seek help, and (f) personal characteristics. The study highlights the importance of barriers and facilitators to be taken into consideration in order to promote the use of mental health services for women with elevated symptoms of depression in the postpartum period. PMID- 27192034 TI - The Mediterranean diet and age-related cognitive functioning: A systematic review of study findings and neuropsychological assessment methodology. AB - OBJECTIVES: The primary aims of this review were to identify studies investigating the association between the MedDiet pattern and age-related cognitive function, to determine the current status of knowledge, and to ascertain whether a lack of standardization with the operationalization of age related cognitive function and differences in the chosen neuropsychological assessment methodology impacted on the results and findings. METHODS: The systematic review protocol for this paper was carried out following the statement and general principles of PRISMA and the UK Centre for Reviews and Dissemination (CRD). RESULTS: A systematic search of electronic databases yielded two cross sectional studies, two cross-sectional/prospective studies, and 11 prospective studies for inclusion. Among this group of studies, conflicting results and conclusions regarding the efficacy of the MedDiet as a therapeutic approach for age-related cognitive function were found. Of importance, clear differences among studies in relation to neuropsychological assessment methodology were identified. Such disparity appeared to be one plausible factor contributing to the lack of consensus among study findings. DISCUSSION: One of the important challenges for future research will be to aim toward some kind of standardized neuropsychological assessment criteria. This type of endeavor will enable the ability to validate with greater confidence, whether or not adherence to a MedDiet does promote benefit for age-related cognitive function. PMID- 27192035 TI - Optimization of electrospinning parameters for polyacrylonitrile-MgO nanofibers applied in air filtration. AB - The present study aimed to optimize the electrospinning parameters for polyacrylonitrile (PAN) nanofibers containing MgO nanoparticle to obtain the appropriate fiber diameter and mat porosity to be applied in air filtration. Optimization of applied voltage, solution concentration, and spinning distance was performed using response surface methodology. In total, 15 trials were done according to the prepared study design. Fiber diameter and porosity were measured using scanning electron microscopic (SEM) image analysis. For air filtration testing, the nanofiber mat was produced based on the suggested optimum conditions for electrospinning. According to the results, the lower solution concentration favored the thinner fiber. The larger diameter gave a higher porosity. At a given spinning distance, there was a negative correlation between fiber diameter and applied voltage. Moreover, there were curvilinear relationships between porosity and both spinning distance and applied voltage at any concentration. It was also concluded that the developed filter medium could be comparable to the high efficiency particulate air (HEPA) filter in terms of collection efficiency and pressure drop. The empirical models presented in this study can provide an orientation to the subsequent experiments to form uniform and continuous nanofibers for future application in air purification. IMPLICATIONS: High efficiency filtration is becoming more important, due to decreasing trends air quality. Effective filter media are increasingly needed in industries applying clean-air technologies, and the necessity for developing the high-performance air filters has been more and more felt. Nanofibrous filter media that are mostly fabricated via electrospinning technique have attracted considerable attention in the last decade. The present study aimed to develop the electrospun PAN containing MgO nanoparticle (using the special functionalities such as absorption and adsorption characteristics, antibacterial functionality, and as a pore forming agent) filter medium through experimental investigations for application in high-performance air filters. PMID- 27192033 TI - Functional characterization of SlitPBP3 in Spodoptera litura by CRISPR/Cas9 mediated genome editing. AB - Functional gene analysis by using genome editing techniques is limited only in few model insects. Here, we reported an efficient and heritable gene mutagenesis analysis in an important lepidopteran pest, Spodoptera litura, using the CRISPR/Cas9 system. By using this system, we successfully obtained the homozygous S. litura strain by targeting the pheromone binding protein 3 gene (SlitPBP3), which allowed us to elucidate the role of this gene in the olfaction of the female sex pheromones. By co-injection of Cas9 mRNA and sgRNA into S. litura eggs, highly efficient chimera mutation in SlitPBP3 loci was detected both in injected eggs (39.1%) and in the resulting individual moths (87.5%). We used the mutant moths as parents to obtain the G1 offspring and the homozygous mutant strain in G2. The function of SlitPBP3 was explored by Electroantennogram (EAG) recordings with a homozygous mutant strain. The result showed that the EAG responses were significantly decreased in mutant males than in control males when treated with the major sex pheromone component (Z9,E11-14:Ac) and a minor component (Z9-14:Ac) at higher dosages. The results demonstrate that s SlitPBP3 gene plays a minor role in the perception of the female sex pheromones. Furthermore, our study provides a useful methodology with the CRISPR/Cas9 system for gene in vivo functional study, particular for lepidopteran species in which the RNAi approach is not efficient. PMID- 27192036 TI - X-ray Crystallographic Structure and Solution Behavior of an Antiparallel Coiled Coil Hexamer Formed by de Novo Peptides. AB - The self-assembly of peptides and proteins into higher-ordered structures is encoded in the amino acid sequence of each peptide or protein. Understanding the relationship among the amino acid sequence, the assembly dynamics, and the structure of well-defined peptide oligomers expands the synthetic toolbox for these structures. Here, we present the X-ray crystallographic structure and solution behavior of de novo peptides that form antiparallel coiled-coil hexamers (ACC-Hex) by an interaction motif neither found in nature nor predicted by existing peptide design software. The 1.70 A X-ray crystallographic structure of peptide 1a shows six alpha-helices associating in an antiparallel arrangement around a central axis comprising hydrophobic and aromatic residues. Size exclusion chromatography studies suggest that peptides 1 form stable oligomers in solution, and circular dichroism experiments show that peptides 1 are stable to relatively high temperatures. Small-angle X-ray scattering studies of the solution behavior of peptide 1a indicate an equilibrium of dimers, hexamers, and larger aggregates in solution. The structures presented here represent a new motif of biomolecular self-assembly not previously observed for de novo peptides and suggest supramolecular design principles for material scaffolds based on coiled-coil motifs containing aromatic residues. PMID- 27192038 TI - Periorbital cellulitis in children: Analysis of outcome of intravenous antibiotic therapy. AB - Periorbital cellulitis is a relatively common ocular disease in the pediatric population. Early diagnosis of this disease with a prompt intervention is critical to avoid vision and life-threatening complications. In the last years, medical therapy has been expanding for the treatment of orbital cellulitis, instead of the standard surgical approach. The purpose of this study was to describe the outcome of treatment with intravenous antibiotic of periorbital cellulitis in children. A retrospective review of all children admitted with periorbital cellulitis in our hospital between January 2002 and July 2013 was conducted. Cases were divided in two subgroups, pre-septal and post-septal infection. The demographics, clinical findings, treatment and outcomes were analyzed. In total 110 children were included, 93 with pre-septal and 17 with post-septal cellulitis. The mean age was 3.5 years in children with pre-septal cellulitis and 5.5 years in those with post-septal cellulitis (p = 0.149). For both subgroups the most common predisposing factor was sinusitis. Intravenous antibiotic therapy was successful in all except one patient with an orbital abscess who required surgical intervention. In our study complete recovery was achieve in all (except for one) children with periorbital cellulitis treated with intravenous antibiotics only. PMID- 27192037 TI - Compaction and segregation of sister chromatids via active loop extrusion. AB - The mechanism by which chromatids and chromosomes are segregated during mitosis and meiosis is a major puzzle of biology and biophysics. Using polymer simulations of chromosome dynamics, we show that a single mechanism of loop extrusion by condensins can robustly compact, segregate and disentangle chromosomes, arriving at individualized chromatids with morphology observed in vivo. Our model resolves the paradox of topological simplification concomitant with chromosome 'condensation', and explains how enzymes a few nanometers in size are able to control chromosome geometry and topology at micron length scales. We suggest that loop extrusion is a universal mechanism of genome folding that mediates functional interactions during interphase and compacts chromosomes during mitosis. PMID- 27192039 TI - Natural or replacer sources of milk in lambs during feeding adaptation: influences on performance, metabolism of protein and lipid and oxidative/antioxidant status. AB - This study aimed to evaluate the effect of milk feeding using milk replacer (MR) or natural ewe's milk (NEM) for Lacaune lambs on performance, protein and lipid metabolism and oxidative/antioxidant status. These parameters were evaluated during the period of feeding adaptation, which corresponded to 12 days after ewe's separation. Fifteen lambs were selected and divided into two groups: Group A (n = 7) with lambs receiving natural milk; Group B (n = 8) with lambs receiving a milk replacer. Liquid food supply, for both groups, was set according to their body weight, given in two daily periods. Feed intake was also obtained by individual body weight and adjusted according leftovers. Blood samples were collected on three different days (0, 6 and 12) to perform the serum analysis of total protein, albumin, cholesterol, triglycerides, alanine aminotransferase (ALT) and urea. Additionally, the oxidative profile was analysed in sera samples through the assessment of TBARS (reactive substances thiobarbituric acid) and ROS (reactive oxygen species) which aims to identify lipid peroxidation and free radical levels, respectively, as well as the antioxidant profile evaluating glutathione S-transferase (GST). There was no statistical difference (p > 0.05) between groups on levels of total protein, albumin and globulin. However, cholesterol (day 6), triglycerides (days 6 and 12), urea (day 6) and ALT (day 12) levels differed (p < 0.05) between groups. Values of total protein, globulin, ALT and TBARS differed (p < 0.05) along the time. The average weight gain and body weight differed (p < 0.05) only on day 12, showing that weight gain was higher for lambs fed with NEM. The performance of lambs fed with MR was impaired. Biochemical parameters had a slight variation between groups and along the time, as well as oxidative/antioxidant status did not change in the different liquid diets. PMID- 27192040 TI - Optimized approach to cine MRI of uterine peristalsis. AB - PURPOSE: To determine the optimal slice thickness, playback rate, and scan time for uterine peristalsis with 3.0T magnetic resonance imaging (MRI). MATERIALS AND METHODS: In all, 23 young female volunteers underwent a 3.0T MRI scan with different slice thicknesses of 3 mm (Cine3mm ), 5 mm (Cine5mm ), and 7 mm (Cine7mm ) for 6 minutes. Subjective image quality score, signal-to-noise ratios (SNRs), and contrast-to-noise ratios (CNRs) of those MR images were evaluated by two radiologists independently. The number, intensity, and direction of uterine peristalsis with different thickness were compared at various playback rates. Also, the peristalsis frequency was counted and compared in different acquisition durations (1-6 minutes). RESULTS: The subjective image quality score, peristalsis number, and intensity were significantly higher in Cine7mm and Cine5mm than Cine3mm (P < 0.05), while the SNRs and CNRs of Cine7mm were significantly higher than Cine3mm (P < 0.05). Peristalsis numbers did not differ significantly at different playback rates with the same slice thickness (P = 0.548-0.962). However, peristalsis intensity at 12*, and 15* was significantly greater than that at 8* the actual speed for Cine7mm and Cine5mm (P < 0.05). The peristalsis frequency at 3, 4, 5, 6 minutes was significantly higher than that at 1 minute and 2 minutes (P < 0.05). CONCLUSION: We recommend a slice thickness of 5 mm or 7 mm and a scan time of 3 minutes for uterine peristalsis with 3.0T MRI, and a playback rate of 12* or 15* the actual speed for peristalsis observation. J. Magn. Reson. Imaging 2016;44:1397-1404. PMID- 27192041 TI - Advanced Nursing Process quality: Comparing the International Classification for Nursing Practice (ICNP) with the NANDA-International (NANDA-I) and Nursing Interventions Classification (NIC). AB - AIMS AND OBJECTIVES: To assess the quality of the advanced nursing process in nursing documentation in two hospitals. BACKGROUND: Various standardised terminologies are employed by nurses worldwide, whether for teaching, research or patient care. These systems can improve the quality of nursing records, enable care continuity, consistency in written communication and enhance safety for patients and providers alike. DESIGN: Cross-sectional study. METHODS: A total of 138 records from two facilities (69 records from each facility) were analysed, one using the NANDA-International and Nursing Interventions Classification terminology (Centre 1) and one the International Classification for Nursing Practice (Centre 2), by means of the Quality of Diagnoses, Interventions, and Outcomes instrument. Quality of Diagnoses, Interventions, and Outcomes scores range from 0-58 points. Nursing records were dated 2012-2013 for Centre 1 and 2010-2011 for Centre 2. RESULTS: Centre 1 had a Quality of Diagnoses, Interventions, and Outcomes score of 35.46 (+/-6.45), whereas Centre 2 had a Quality of Diagnoses, Interventions, and Outcomes score of 31.72 (+/-4.62) (p < 0.001). Centre 2 had higher scores in the 'Nursing Diagnoses as Process' dimension, whereas in the 'Nursing Diagnoses as Product', 'Nursing Interventions' and 'Nursing Outcomes' dimensions, Centre 1 exhibited superior performance; acceptable reliability values were obtained for both centres, except for the 'Nursing Interventions' domain in Centre 1 and the 'Nursing Diagnoses as Process' and 'Nursing Diagnoses as Product' domains in Centre 2. CONCLUSION: The quality of nursing documentation was superior at Centre 1, although both facilities demonstrated moderate scores considering the maximum potential score of 58 points. Reliability analyses showed satisfactory results for both standardised terminologies. RELEVANCE TO CLINICAL PRACTICE: Nursing leaders should use a validated instrument to investigate the quality of nursing records after implementation of standardised terminologies. PMID- 27192042 TI - Discrepancies between direct and indirect measures of interpersonal and neurocognitive skills in autism spectrum disorder children. AB - BACKGROUND: Subjects with autistic spectrum disorders (ASD) show persistent deficits in social interaction. In order to explore the scope of their deficits, it is of great interest to compare the different interpersonal skills and executive functions of ASD subjects to those of children with typical development. Assessing these skills usually involves a large variety of informants (parents, teachers, other family members) and of measures, with frequent discrepancies between direct performance measures and indirect measures (third-party report). Different explanations of this mismatch between measures have been addressed in previous studies. OBJECTIVES: We wish to analyze whether there are differences between children with ASD and children with typical development on several direct performance measures of interpersonal and neurocognitive skills and one third-party report on real-life performance of interpersonal skills; we also want to look at whether discrepancies appear between the two types of measurements in the two groups of participants. METHOD: A total of 68 Spanish children between the ages of 7 and 12 years participated; 34 were children with ASD, and 34 showed typical development. All participants were tested for recognition of emotions, solving interpersonal conflicts, and executive function. RESULTS: Significant differences between the two groups were not found on most of the direct performance measures, but they did appear in the report by third parties, in favor of the group with typical development. There was also a significant association between neurocognitive and social variables in the latter group. CONCLUSIONS: There were intergroup differences and discrepancies between the direct performance and indirect measures in children with ASD, and these must be explained. For this reason, future studies could seek to explain the cause of these discrepancies with a greater number of measures for each of the skills. PMID- 27192043 TI - Integration of Genomic and Other Epidemiologic Data to Investigate and Control a Cross-Institutional Outbreak of Streptococcus pyogenes. AB - Single-strain outbreaks of Streptococcus pyogenes infections are common and often go undetected. In 2013, two clusters of invasive group A Streptococcus (iGAS) infection were identified in independent but closely located care homes in Oxfordshire, United Kingdom. Investigation included visits to each home, chart review, staff survey, microbiologic sampling, and genome sequencing. S. pyogenes emm type 1.0, the most common circulating type nationally, was identified from all cases yielding GAS isolates. A tailored whole-genome reference population comprising epidemiologically relevant contemporaneous isolates and published isolates was assembled. Data were analyzed independently using whole-genome multilocus sequencing and single-nucleotide polymorphism analyses. Six isolates from staff and residents of the homes formed a single cluster that was separated from the reference population by both analytical approaches. No further cases occurred after mass chemoprophylaxis and enhanced infection control. Our findings demonstrate the ability of 2 independent analytical approaches to enable robust conclusions from nonstandardized whole-genome analysis to support public health practice. PMID- 27192045 TI - Access to and characteristics of palliative care-related hospitalization in the management of end-stage renal disease patients on renal replacement therapy in France. AB - AIM: Palliative care is seldom proposed to patients with end-stage renal disease (ESRD) despite a mortality rate and disease burden as high as among cancer patients. The aim of this study is to analyze the access of palliative care related hospitalization in the management of patients on dialysis in France, by describing the characteristics of these hospitalizations, the clinical status of the concerned patients, and the use of palliative care in those stopping dialysis. METHODS: The French Renal Epidemiology and Information Network (REIN) registry includes data about 51 834 patients aged 20 years and older who began dialysis from 1 January 2008 to 31 December 2013, and were followed longitudinally until that date. Linkage to the anonymized national hospital discharge database allowed us to analyse hospitalizations associated with palliative care. RESULTS: During the follow-up period, 1865 patients (3.6%) had a palliative care-related hospitalization corresponding to a total of 3382 hospitalizations. Lower levels of serum albumin, active cancer, and impaired mobility were each independently associated with the probability of at least one such hospitalization. During the same period 4540 patients withdrew from dialysis (9% of the patients), 10% of them had a palliative care-related hospitalization. CONCLUSION: This study suggests that among ESRD patients, only a few resorted to palliative care-related hospitalization, even those withdrawing from dialysis. Cooperation between nephrologists and physicians trained in palliative care should be improved at least to the extent necessary to identify patients who should be referred to palliative care. Our study also highlights the need for more information on the current access to any kind of supportive care for dialysis patients. PMID- 27192044 TI - Gestation related karyotype, QF-PCR and CGH-array failure rates in diagnostic amniocentesis. AB - BACKGROUND: Few data exist describing laboratory related failure rates in prenatal diagnosis. The aim of this study is to assess the laboratory associated failure rate for karyotype, QF-PCR and CGH-array following amniocentesis in relation to gestation. METHODS: Retrospective database study of amniocenteses performed 2004-2014 comparing laboratory failure rate for karyotype, QF-PCR and CGH-array between 16 + 0 and 40 + 0 weeks' gestation. RESULTS: A total of 10 484 amniotic fluid test results were collected in three databases. Karyotype failed in 41/1797 (2.3%) tests; failure rate was significantly greater with advancing gestation reaching 43% at 36-40 weeks. QF-PCR failed in 132/5715 tests (2.3%) and was significantly greater with advancing gestation reaching 7% at 36-40 weeks. For CGH-array, 10/298 tests (3.4%) failed analysis. In one case, no result was obtainable by any technique. CONCLUSIONS: These data provide gestation specific laboratory failure rates for amniocentesis enabling informed decisions about the timing and laboratory technique most applicable to the clinical situation. Before 20 weeks, karyotype is least likely to fail of the three techniques. However, in the late third trimester, QF-PCR and, in particular, karyotyping are more likely to fail than CGH-array. Although there is some overlap between the three different tests, they may be preferentially offered in different clinical scenarios. (c) 2016 John Wiley & Sons, Ltd. PMID- 27192046 TI - Ophthalmic diagnostic testing and examination findings in a colony of captive brown pelicans (Pelecanus occidentalis). AB - OBJECTIVE: To establish reference values and report ophthalmic examination findings in a colony of captive brown pelicans (Pelecanus occidentalis). DESIGN: Descriptive study. ANIMALS STUDIED: Sixty-three captive brown pelicans in Florida were examined. PROCEDURES: A complete ophthalmic examination including Schirmer tear test (STT), applanation tonometry, fluorescein stain, biomicroscopy, and direct and indirect ophthalmoscopy was performed. A-scan ultrasonography was performed to measure axial globe length (AGL), anterior chamber depth (ACD), lens thickness, and vitreal chamber length. Fifty-two adults and 11 juvenile pelicans with an age range of 4 months to 38 years were evaluated. RESULTS: Twenty-nine pelicans (46%) had a normal ocular examination. Mean STT in normal pelicans was 5.45 +/- 1.88 mm/min. Mean intraocular pressure (IOP) in normal pelicans was 10.86 +/- 1.61 mmHg. One pelican was fluorescein positive unilaterally. Mean AGL was 20.70 +/- 0.62 mm. Mean ACD was 3.38 +/- 0.19 mm. Mean axial lens diameter (ALD) was 5.19 +/- 0.23 mm. Mean vitreal chamber depth (VCD) was 12.15 +/- 0.53 mm. Twenty-three pelicans (36.51%) had cataracts, 17 pelicans (26.98%) had vitreal degeneration, 18 pelicans (28.57%) had corneal disease, and seven pelicans (11.11%) had evidence of significant ocular trauma, which included collapsed anterior chamber or lens luxation. CONCLUSIONS AND CLINICAL RELEVANCE: To the author's knowledge, this is the first report of normal ophthalmic parameters and the incidence and type of ocular disease in a captive flock of brown pelicans. This information may aid in the diagnosis and treatment of brown pelicans with ocular disease. PMID- 27192047 TI - Exercise intolerance in pulmonary hypertension: mechanism, evaluation and clinical implications. AB - INTRODUCTION: Exercise intolerance in pulmonary hypertension (PH) is a major factor affecting activities of daily living and quality of life. Evaluation strategies (i.e., non-invasive and invasive tests) are integral to providing a comprehensive assessment of clinical and functional status. Despite a growing body of literature on the clinical consequences of PH, there are limited studies discussing the contribution of various physiological systems to exercise intolerance in this patient population. AREAS COVERED: This review, through a search of various databases, describes the physiological basis for exercise intolerance across the various PH etiologies, highlights the various exercise evaluation methods and discusses the rationale for exercise training amongst those diagnosed with PH. Expert commentary: With the growing importance of evaluating exercise capacity in PH (class 1, Level C recommendation), understanding why exercise performance is altered in PH is crucial. Thus, the further study is required for better quality evidence in this area. PMID- 27192048 TI - Cinnamomum verum ingredient 2-methoxycinnamaldehyde: a new antiproliferative drug targeting topoisomerase I and II in human lung squamous cell carcinoma NCI-H520 cells. AB - Cinnamomum verum has been used as a Chinese herbal medication. We investigated the antiproliferative effect of 2-methoxycinnamaldehyde (2-MCA), a constituent of the cortex of the plant, and the molecular biomarkers associated with tumorigenesis in human lung squamous cell carcinoma NCI-H520 cells. The effects of 2-MCA on cell growth, cytotoxicity, apoptosis, and topoisomerase I and II activities in human lung squamous cell carcinoma NCI-H520 cells were evaluated in vitro and in vivo. The results showed that 2-MCA inhibited proliferation and induced apoptosis as implicated by mitochondrial membrane potential (DeltaPsim) loss, activation of both caspase 3 and caspase 9, as well as morphological characteristics of apoptosis. Furthermore, 2-MCA also induced lysosomal vacuolation with elevated volume of acidic compartment and cytotoxicity, and inhibited topoisomerase I as well as II activities. Additional study showed the antiproliferative effect of 2-MCA in a nude mice model. In short, our data imply that the antiproliferative activity of 2-MCA in vitro involved downregulation of cell growth markers, both topoisomerase I and II, and upregulation of proapoptotic molecules, associated with increased lysosomal vacuolation. In vivo, 2-MCA reduced the tumor size, which could have had a significant clinical impact. Our data imply that 2-MCA may be a potential agent for chemoprevention as well as anticancer therapy. PMID- 27192049 TI - Correction: Morphogenesis of the C. elegans Intestine Involves Axon Guidance Genes. AB - [This corrects the article DOI: 10.1371/journal.pgen.1005950.]. PMID- 27192050 TI - Attention-Deficit/Hyperactivity Disorder Trajectories From Childhood to Young Adulthood: Evidence From a Birth Cohort Supporting a Late-Onset Syndrome. AB - IMPORTANCE: The requirement of a childhood onset has always been a key criterion for the diagnosis of attention-deficit/hyperactivity disorder (ADHD) in adults, but recently this requirement has become surrounded by controversy. OBJECTIVE: To investigate whether impaired young adults with ADHD symptoms always have a childhood-onset disorder in a population-based longitudinal study. DESIGN, SETTING, AND PARTICIPANTS: Participants belonged to the 1993 Pelotas Birth Cohort Study, including 5249 individuals born in Pelotas, Brazil, in 1993. They were followed up to 18 to 19 years of age, with 81.3% retention. The data analysis was performed between August 8, 2015, and February 5, 2016. MAIN OUTCOMES AND MEASURES: The ADHD status was first ascertained at 11 years of age using a screening instrument (hyperactivity subscale of the Strength and Difficulties Questionnaire) calibrated for a DSM-IV ADHD diagnosis based on clinical interviews with parents using the Development and Well-Being Assessment. At 18 to 19 years of age, ADHD diagnosis was derived using DSM-5 criteria, except age at onset. We estimated the overlap between these groups assessed at 11 and 18 to 19 years of age and the rates of markers of impairment in these 2 groups compared with those without ADHD. RESULTS: At 11 years of age, childhood ADHD (C-ADHD) was present in 393 individuals (8.9%). At 18 to 19 years of age, 492 individuals (12.2%) fulfilled all DSM-5 criteria for young adult ADHD (YA-ADHD), except age at onset. After comorbidities were excluded, the prevalence of YA-ADHD without comorbidities decreased to 256 individuals (6.3%). Children with C-ADHD had a male preponderance not observed among children without ADHD (251 [63.9%] vs 1930 [47.9%] male, P < .001), whereas the YA-ADHD group had a female preponderance (192 [39.0%] vs 1786 [50.4%] male, P < .001). Both groups had increased levels of impairment in adulthood, as measured by traffic incidents, criminal behavior, incarceration, suicide attempts, and comorbidities. However, only 60 children (17.2%) with ADHD continued to have ADHD as young adults, and only 60 young adults (12.6%) with ADHD had the disorder in childhood. CONCLUSIONS AND RELEVANCE: The findings of this study do not support the assumption that adulthood ADHD is necessarily a continuation of childhood ADHD. Rather, they suggest the existence of 2 syndromes that have distinct developmental trajectories. PMID- 27192051 TI - Cost-Effectiveness Analysis of Screening for and Managing Identified Hypertension for Cardiovascular Disease Prevention in Vietnam. AB - OBJECTIVE: To inform development of guidelines for hypertension management in Vietnam, we evaluated the cost-effectiveness of different strategies on screening for hypertension in preventing cardiovascular disease (CVD). METHODS: A decision tree was combined with a Markov model to measure incremental cost-effectiveness of different approaches to hypertension screening. Values used as input parameters for the model were taken from different sources. Various screening intervals (one-off, annually, biannually) and starting ages to screen (35, 45 or 55 years) and coverage of treatment were analysed. We ran both a ten-year and a lifetime horizon. Input parameters for the models were extracted from local and regional data. Probabilistic sensitivity analysis was used to evaluate parameter uncertainty. A threshold of three times GDP per capita was applied. RESULTS: Cost per quality adjusted life year (QALY) gained varied in different screening scenarios. In a ten-year horizon, the cost-effectiveness of screening for hypertension ranged from cost saving to Int$ 758,695 per QALY gained. For screening of men starting at 55 years, all screening scenarios gave a high probability of being cost-effective. For screening of females starting at 55 years, the probability of favourable cost-effectiveness was 90% with one-off screening. In a lifetime horizon, cost per QALY gained was lower than the threshold of Int$ 15,883 in all screening scenarios among males. Similar results were found in females when starting screening at 55 years. Starting screening in females at 45 years had a high probability of being cost-effective if screening biannually was combined with increasing coverage of treatment by 20% or even if sole biannual screening was considered. CONCLUSION: From a health economic perspective, integrating screening for hypertension into routine medical examination and related coverage by health insurance could be recommended. Screening for hypertension has a high probability of being cost-effective in preventing CVD. An adequate screening strategy can best be selected based on age, sex and screening interval. PMID- 27192053 TI - Correction: Two-Level Scheduling for Video Transmission over Downlink OFDMA Networks. AB - [This corrects the article DOI: 10.1371/journal.pone.0148625.]. PMID- 27192052 TI - Detectable HIV Viral Load in Kenya: Data from a Population-Based Survey. AB - INTRODUCTION: At the individual level, there is clear evidence that Human Immunodeficiency Virus (HIV) transmission can be substantially reduced by lowering viral load. However there are few data describing population-level HIV viremia especially in high-burden settings with substantial under-diagnosis of HIV infection. The 2nd Kenya AIDS Indicator Survey (KAIS 2012) provided a unique opportunity to evaluate the impact of antiretroviral therapy (ART) coverage on viremia and to examine the risks for failure to suppress viral replication. We report population-level HIV viral load suppression using data from KAIS 2012. METHODS: Between October 2012 to February 2013, KAIS 2012 surveyed household members, administered questionnaires and drew serum samples to test for HIV and, for those found to be infected with HIV, plasma viral load (PVL) was measured. Our principal outcome was unsuppressed HIV viremia, defined as a PVL >= 550 copies/mL. The exposure variables included current treatment with ART, prior history of an HIV diagnosis, and engagement in HIV care. All point estimates were adjusted to account for the KAIS 2012 cluster sampling design and survey non response. RESULTS: Overall, 61.2% (95% CI: 56.4-66.1) of HIV-infected Kenyans aged 15-64 years had not achieved virological suppression. The base10 median (interquartile range [IQR]) and mean (95% CI) VL was 4,633 copies/mL (0-51,596) and 81,750 copies/mL (59,366-104,134), respectively. Among 266 persons taking ART, 26.1% (95% CI: 20.0-32.1) had detectable viremia. Non-ART use, younger age, and lack of awareness of HIV status were independently associated with significantly higher odds of detectable viral load. In multivariate analysis for the sub-sample of patients on ART, detectable viremia was independently associated with younger age and sub-optimal adherence to ART. DISCUSSION: This report adds to the limited data of nationally-representative surveys to report population- level virological suppression. We established heterogeneity across the ten administrative and HIV programmatic regions on levels of detectable viral load. Timely initiation of ART and retention in care are crucial for the elimination of transmission of HIV through sex, needle and syringe use or from mother to child. Further refinement of geospatial mapping of populations with highest risk of transmission is necessary. PMID- 27192054 TI - A Survey of N'-Nitrosonornicotine (NNN) and Total Water Content in Select Smokeless Tobacco Products Purchased in the United States in 2015. AB - This investigation provides an updated survey measuring the levels of N' nitrosonornicotine (NNN) and water content of a select number of smokeless tobacco products sold in the United States in 2015. A total of 34 smokeless tobacco products were collected and analyzed for NNN and water content using LC MS/MS and GC-TCD, respectively. Smokeless tobacco products were chosen to obtain a representative sample of the different types of products on the U.S. market. These smokeless products represent 12 of the 25 top-selling smokeless tobacco products according to 2013 Nielsen net sales data while five of the smokeless tobacco products are of lower selling smokeless tobacco products. The NNN levels and the water content of the smokeless tobacco products were determined and compared to previous studies. Although the range of NNN levels found was broad for the examined smokeless tobacco products (0.64-12.0 MUg/g dry weight), dry snuff had the highest levels of NNN observed (>5 MUg/g dry weight). We observed a general decrease in NNN levels for the same six moist snuff products that were analyzed in 2004 compared to our current 2015 study. The water content of the smokeless tobacco products surveyed ranged from 3.92 to 54.8%. PMID- 27192056 TI - Correction: Effects of a Closed Space Environment on Gene Expression in Hair Follicles of Astronauts in the International Space Station. AB - [This corrects the article DOI: 10.1371/journal.pone.0150801.]. PMID- 27192055 TI - Open-label, multicenter, phase 1 study of alisertib (MLN8237), an aurora A kinase inhibitor, with docetaxel in patients with solid tumors. AB - BACKGROUND: This study was designed to determine the safety, tolerability, and pharmacokinetics (PK) of alisertib (MLN8237) in combination with docetaxel and to identify a recommended dose for the combination. METHODS: Adults with metastatic cancer were treated on 21-day cycles with alisertib (10, 20, 30, or 40 mg) twice daily on days 1 to 7 or days 1 to 5 and with docetaxel (75 or 60 mg/m(2) ) on day 1. The primary objectives were to assess the safety and tolerability of the combination and to determine the recommended phase 2 dose (RP2D) for future studies. Secondary objectives included an efficacy assessment and PK analyses of docetaxel and alisertib. RESULTS: Forty-one patients participated. Eight dose levels were explored with various doses of alisertib and docetaxel. The dose limiting toxicities were neutropenic fever, neutropenia without fever, stomatitis, and urinary tract infection. The RP2D of this combination was 20 mg of alisertib twice daily on days 1 to 7 and intravenous docetaxel at 75 mg/m(2) on day 1 in 21-day cycles. Eight of the 28 patients (29%) who were efficacy evaluable had objective responses. These included 1 complete response in a patient with bladder cancer, 6 partial responses in patients with castration resistant prostate cancer, and 1 partial response in a patient with angiosarcoma. Concomitant administration of alisertib did not produce any clinically meaningful change in docetaxel PK. CONCLUSIONS: Alisertib at 20 mg twice daily on days 1 to 7 with intravenous docetaxel at 75 mg/m(2) on day 1 in a 21-day cycle was well tolerated, and the combination demonstrated antitumor activity. Cancer 2016;122:2524-33. (c) 2016 American Cancer Society. PMID- 27192058 TI - Low quality of dying and death in patients with septic shock as perceived by nurses and resident physicians. AB - Septic shock is a disease with both high prevalence and mortality. Few studies have evaluated the quality of dying and death (QODD) in patients with septic shock. The authors compared the QODD of patients who died of septic shock versus other causes. They prospectively collected QODD surveys from nurses and residents caring for 196 patients who died in the medical intensive care unit (ICU) at an urban, university hospital. Patients were included in the analysis if either a nurse or resident returned a survey. Chart review established cause of death. The authors compared total QODD scores (on a scale of 0-100) and a single-item score (QODD-1; on a scale of 0-10) of patients who died of septic shock versus other causes. Survey response rates were 59% (n = 155) for residents and 49% (n = 129) for nurses. Nurses rated patients as having lower total QODD and QODD-1 scores for septic (Delta 7.5 points, p = 0.03, and 0.9 points, p = 0.05, respectively). Residents rated septic patients with lower QODD-1 scores than nonseptic patients (Delta 0.8 points, p = 0.03). This study shows that nurses rate patients with septic shock as having lower QODD than patients dying of other causes. These findings are important for clinicians who counsel families of patients dying of septic shock. PMID- 27192059 TI - DEFENDER: Detecting and Forecasting Epidemics Using Novel Data-Analytics for Enhanced Response. AB - In recent years social and news media have increasingly been used to explain patterns in disease activity and progression. Social media data, principally from the Twitter network, has been shown to correlate well with official disease case counts. This fact has been exploited to provide advance warning of outbreak detection, forecasting of disease levels and the ability to predict the likelihood of individuals developing symptoms. In this paper we introduce DEFENDER, a software system that integrates data from social and news media and incorporates algorithms for outbreak detection, situational awareness and forecasting. As part of this system we have developed a technique for creating a location network for any country or region based purely on Twitter data. We also present a disease nowcasting (forecasting the current but still unknown level) approach which leverages counts from multiple symptoms, which was found to improve the nowcasting accuracy by 37 percent over a model that used only previous case data. Finally we attempt to forecast future levels of symptom activity based on observed user movement on Twitter, finding a moderate gain of 5 percent over a time series forecasting model. PMID- 27192057 TI - Molecular Characterization and Function Analysis of the Vitellogenin Receptor from the Cotton Bollworm, Helicoverpa armigera (Hubner) (Lepidoptera, Noctuidae). AB - Developing oocytes accumulate plentiful yolk protein during oogenesis through receptor-mediated endocytosis. The vitellogenin receptor (VgR), belonging to the low-density lipoprotein receptor (LDLR) family, regulates the absorption of yolk protein. In this work, the full-length vitellogenin receptor (HaVgR) in the cotton bollworm Helicoverpa armigera was identified, encoding a 1817 residue protein. Sequence alignment revealed that the sequence of HaVgR contained all of the conservative structural motifs of LDLR family members, and phylogenetic analysis indicated that HaVgR had a high identity among Lepidoptera and was distinct from that of other insects. Consistent with other insects, HaVgR was specifically expressed in ovarian tissue. The developmental expression pattern showed that HaVgR was first transcribed in the newly metamorphosed female adults, reached a peak in 2-day-old adults and then declined. Western blot analysis also revealed an ovarian-specific and developing expression pattern, which was consistent with the HaVgR mRNA transcription. Moreover, RNAi-mediated HaVgR knockdown strongly reduced the VgR expression in both the mRNA and protein levels, which inhibited the yolk protein deposition in the ovaries, led to the dramatic accumulation of vitellogenin and the up-regulation of HaVg expression in hemolymph, and eventually resulted in a declined fecundity. Together, all of these findings demonstrate that HaVgR is a specific receptor in uptake and transportation of yolk protein for the maturation of oocytes and that it plays a critical role in female reproduction. PMID- 27192060 TI - Taking Perspective: Personal Pronouns Affect Experiential Aspects of Literary Reading. AB - Personal pronouns have been shown to influence cognitive perspective taking during comprehension. Studies using single sentences found that 3rd person pronouns facilitate the construction of a mental model from an observer's perspective, whereas 2nd person pronouns support an actor's perspective. The direction of the effect for 1st person pronouns seems to depend on the situational context. In the present study, we investigated how personal pronouns influence discourse comprehension when people read fiction stories and if this has consequences for affective components like emotion during reading or appreciation of the story. We wanted to find out if personal pronouns affect immersion and arousal, as well as appreciation of fiction. In a natural reading paradigm, we measured electrodermal activity and story immersion, while participants read literary stories with 1st and 3rd person pronouns referring to the protagonist. In addition, participants rated and ranked the stories for appreciation. Our results show that stories with 1st person pronouns lead to higher immersion. Two factors-transportation into the story world and mental imagery during reading-in particular showed higher scores for 1st person as compared to 3rd person pronoun stories. In contrast, arousal as measured by electrodermal activity seemed tentatively higher for 3rd person pronoun stories. The two measures of appreciation were not affected by the pronoun manipulation. Our findings underscore the importance of perspective for language processing, and additionally show which aspects of the narrative experience are influenced by a change in perspective. PMID- 27192061 TI - Female Zebra Finches Smell Their Eggs. AB - Parental investment in unrelated offspring seems maladaptive from an evolutionary perspective, due to the costs of energy and resources that cannot be invested in related offspring at the same time. Therefore selection should favour mechanisms to discriminate between own and foreign offspring. In birds, much emphasis has been placed on understanding the visual mechanisms underlying egg recognition. However, olfactory egg recognition has almost been completely ignored. Here, we investigated whether female zebra finches (Taeniopygia guttata) are able to discriminate between their own and a conspecific egg based on olfactory cues alone. Zebra finches are colonial-breeding songbirds. Eggs are monomorphic, i.e. without any spotting pattern, and intraspecific brood parasitism frequently occurs. In a binary choice experiment, female zebra finches were given the choice between the scent of their own and a conspecific egg. After the onset of incubation, females chose randomly and showed no sign of discrimination. However, shortly before hatching, females preferred significantly the odour of their own egg. The finding that females are capable to smell their own egg may inspire more research on the potential of olfaction involved in egg recognition, especially in cases where visual cues might be limited. PMID- 27192062 TI - Inference for binomial probability based on dependent Bernoulli random variables with applications to meta-analysis and group level studies. AB - We study bias arising as a result of nonlinear transformations of random variables in random or mixed effects models and its effect on inference in group level studies or in meta-analysis. The findings are illustrated on the example of overdispersed binomial distributions, where we demonstrate considerable biases arising from standard log-odds and arcsine transformations of the estimated probability p, both for single-group studies and in combining results from several groups or studies in meta-analysis. Our simulations confirm that these biases are linear in rho, for small values of rho, the intracluster correlation coefficient. These biases do not depend on the sample sizes or the number of studies K in a meta-analysis and result in abysmal coverage of the combined effect for large K. We also propose bias-correction for the arcsine transformation. Our simulations demonstrate that this bias-correction works well for small values of the intraclass correlation. The methods are applied to two examples of meta-analyses of prevalence. PMID- 27192063 TI - ECDYSTEROID AND CHITINASE FLUCTUATIONS IN THE WESTERN TARNISHED PLANT BUG (Lygus hesperus) PRIOR TO MOLT INDICATE ROLES IN DEVELOPMENT. AB - Vital physiological processes that drive the insect molt represent areas of interest for the development of alternative control strategies. The western tarnished plant bug (Lygus hesperus Knight) is a pest of numerous agronomic and horticultural crops but the development of novel control approaches is impeded by limited knowledge of the mechanisms regulating its molt. To address this deficiency, we examined the fundamental relationship underlying the hormonal and molecular components of ecdysis. At 27 degrees C L. hesperus exhibits a temporally controlled nymph-adult molt that occurs about 4 days after the final nymph-nymph molt with ecdysteroid levels peaking 2 days prior to the final molt. Application of exogenous ecdysteroids when endogenous levels had decreased disrupted the nymphal-adult molt, with treated animals exhibiting an inability to escape the old exoskeleton and resulting in mortality compared to controls. Using accessible transcriptomic data, we identified 10 chitinase-like sequences (LhCht), eight of which had protein motifs consistent with chitinases. Phylogenetic analyses revealed orthologous relationships to chitinases critical to molting in other insects. RT-PCR based transcript profiling revealed that expression changes to four of the LhChts was coordinated with the molt period and ecdysteroid levels. Collectively, our results support a role for ecdysteroid regulation of the L. hesperus molt and suggest that cuticle clearance is mediated by LhCht orthologs of chitinases that are essential to the molt process. These results provide the initial hormonal and molecular basis for future studies to investigate the specific roles of these components in molting. PMID- 27192066 TI - Integrating supportive and palliative care for young adults with serious illnesses. PMID- 27192064 TI - Polarized trafficking of the sorting receptor SorLA in neurons and MDCK cells. AB - The sorting receptor SorLA is highly expressed in neurons and is also found in other polarized cells. The receptor has been reported to participate in the trafficking of several ligands, some of which are linked to human diseases, including the amyloid precursor protein, TrkB, and Lipoprotein Lipase (LpL). Despite this, only the trafficking in nonpolarized cells has been described so far. Due to the many differences between polarized and nonpolarized cells, we examined the localization and trafficking of SorLA in epithelial Madin-Darby canine kidney (MDCK) cells and rat hippocampal neurons. We show that SorLA is mainly found in sorting endosomes and on the basolateral surface of MDCK cells and in the somatodendritic domain of neurons. This polarized distribution of SorLA respectively depends on an acidic cluster and an extended version of this cluster and involves the cellular adaptor complex AP-1. Furthermore, we show that SorLA can mediate transcytosis across a tight cell layer. PMID- 27192068 TI - Lateral violence: How educators can help break the cycle. PMID- 27192070 TI - Acute kidney injury: Limiting the damage. PMID- 27192071 TI - Looking into oropharyngeal dysphagia in older adults. PMID- 27192072 TI - The man in the yellow slicker: A clinical chaplain's reflection on nursing and patient care. PMID- 27192073 TI - Using social media to increase engagement in nursing organizations. PMID- 27192074 TI - Update: Pediatric Basic Life Support and Advanced Life Support guidelines. PMID- 27192075 TI - Robotic pet therapy in long-term care. PMID- 27192076 TI - Substance abuse and the law: A case study. PMID- 27192077 TI - Listen up for safe ear irrigation. PMID- 27192079 TI - Online resources for HIV/AIDS. PMID- 27192078 TI - Evaluating pain management in older adults. PMID- 27192080 TI - Vaccines and immune globulins. PMID- 27192083 TI - Electrocatalytic (Bio)Nanostructures Based on Polymer-Grafted Platinum Nanoparticles for Analytical Purpose. AB - Functionalized platinum nanoparticles (PtNPs) possess electrocatalytic properties toward H2O2 oxidation, which are of great interest for the construction of electrochemical oxidoreductase-based sensors. In this context, we have shown that polymer-grafted PtNPs could efficiently be used as building bricks for electroactive structures. In the present work, we prepared different 2D nanostructures based on these elementary bricks, followed by the subsequent grafting of enzymes. The aim was to provide well-defined architectures to establish a correlation between their electrocatalytic properties and the arrangement of building bricks. Two different nanostructures have been elaborated via the smart combination of surface initiated-atom transfer radical polymerization (SI-ATRP), functionalized PtNPs (Br-PtNPs) and Langmuir-Blodgett (LB) technique. The first nanostructure (A) has been elaborated from LB films of poly(methacrylic acid)-grafted PtNPs (PMAA-PtNPs). The second nanostructure (B) consisted in the elaboration of polymer brushes (PMAA brushes) from Br-PtNPs LB films. In both systems, grafting of the glucose oxidase (GOx) has been performed directly to nanostructures, via peptide bonding. Structural features of nanostructures have been carefully characterized (compression isotherms, neutron reflectivity, and profilometry) and correlated to their electrocatalytic properties toward H2O2 oxidation or glucose sensing. PMID- 27192084 TI - Exercise Ameliorates Endocrine Pancreas Damage Induced by Chronic Cola Drinking in Rats. AB - PURPOSE: This study evaluates whether the daily practice of an exercise routine might protect from endocrine pancreas damage in cola drinking rats. METHODS: Forty-eight Wistar rats were randomly assigned to 4 groups depending on a) beverage consumption ad libitum, water (W) or cola beverage (C), and b) physical activity, sedentary (S) or treadmill running (R). Accordingly, 4 groups were studied: WS (water sedentary), WR (water runner), CS (cola sedentary) and CR (cola runner). Body weight, nutritional data, plasma levels of glucose, creatinine, total cholesterol and cholesterol fractions, and triglycerides (enzymocolorimetry), and systolic blood pressure (plethysmography) were measured. After 6 months, euthanasia was performed (overdose sodium thiopental). Pancreatic tissue was immediately excised and conventionally processed for morphometrical and immunohistochemical determinations. RESULTS: The effects of running and chronic cola drinking on pancreas morphology showed interaction (p<0.001) rather than simple summation. Cola drinking (CS vs WS) reduced median pancreatic islet area (-30%, 1.8 10(4) MUm2 vs 2.58 10(4) MUm2, p<0.0001) and median beta-cell mass (-43%, 3.81 mg vs 6.73 mg, p<0.0001), and increased median alpha/beta ratio (+49%, 0.64 vs 0.43, p< 0.001). In water drinking rats (WR vs WS), running reduced median alpha-cell mass (-48%, 1.48 mg vs 2.82 mg, p<0.001) and alpha/beta ratio (-56%, 0.19 vs 0.43, p<0.0001). Differently, in cola drinking rats (CR vs CS), running partially restored median islet area (+15%, 2.06 10(4) MUm2 vs 1.79 10(4) MUm2, p<0.05), increased median beta-cell mass (+47%, 5.59 mg vs 3.81 mg, p <0.0001) and reduced median alpha/beta ratio (-6%, 0.60 vs 0.64, p<0.05). CONCLUSION: This study is likely the first reporting experimental evidence of the beneficial effect of exercise on pancreatic morphology in cola-drinking rats. Presently, the increase of nearly 50% in beta cells mass by running in cola drinking rats is by far the most relevant finding. Moderate running, advisably indicated in cola consumers and patients at risk of diabetes, finds here experimental support. PMID- 27192085 TI - Elevational Distribution of Flightless Ground Beetles in the Tropical Rainforests of North-Eastern Australia. AB - Understanding how the environment influences patterns of diversity is vital for effective conservation management, especially in a changing global climate. While assemblage structure and species richness patterns are often correlated with current environmental factors, historical influences may also be considerable, especially for taxa with poor dispersal abilities. Mountain-top regions throughout tropical rainforests can act as important refugia for taxa characterised by low dispersal capacities such as flightless ground beetles (Carabidae), an ecologically significant predatory group. We surveyed flightless ground beetles along elevational gradients in five different subregions within the Australian Wet Tropics World Heritage Area to investigate (1) whether the diversity and composition of flightless ground beetles are elevationally stratified, and, if so, (2) what environmental factors (other than elevation per se) are associated with these patterns. Generalised linear models and model averaging techniques were used to relate patterns of diversity to environmental factors. Unlike most taxonomic groups, flightless ground beetles increased in species richness and abundance with elevation. Additionally, each subregion consisted of relatively distinct assemblages containing a high level of regional endemic species. Species richness was most strongly and positively associated with historical and current climatic stabilities and negatively associated with severity of recent disturbance (treefalls). Assemblage composition was associated with latitude and historical and current climatic conditions. Although the results need to be interpreted carefully due to inter-correlation between historical and current climatic variables, our study is in agreement with the hypothesis that upland refugia provided stable climatic conditions since the last glacial maximum, and supported a diverse fauna of flightless beetle species. These findings are important for conservation management as upland habitats become increasingly threatened by climate change. PMID- 27192082 TI - Task and Resting-State fMRI Reveal Altered Salience Responses to Positive Stimuli in Patients with Major Depressive Disorder. AB - Altered brain function in patients with major depressive disorder (MDD) has been repeatedly demonstrated by task-based and resting-state studies, respectively. However, less is known concerning whether overlapped abnormalities in functional activities across modalities exist in MDD patients. To find out the answer, we implemented an fMRI experiment and collected both task and resting-state data from 19 MDD patients and 19 matched, healthy, controls. A distraction paradigm involving emotionally valenced pictures was applied to induce affective responses in subjects. As a result, concurrent deficits were found in arousing activation during a positive task in both the reward circuit and salience network (SN) that is composed of the dorsal part of anterior cingulate cortex (dACC) and bilateral anterior insulae (AI) in only the MDD group. Subsequent amplitude of low frequency fluctuations (ALFF) and functional connectivity analyses based on resting-state data exhibited consistent alterations in the bilateral AI of MDD patients, and indicated patients' difficulties in regulating the balance between central executive network (CEN) and default mode network (DMN) due to altered connectivity among the CEN, DMN, and SN. Our findings provide new evidence demonstrating impaired salience processing and resulting alterations in responses to positive stimuli in MDD patients. Furthermore, brain abnormalities synchronized across functional states in MDD patients can be evidenced by a combination of task and resting-state fMRI analyses. PMID- 27192087 TI - Issue highlights - May 2016. PMID- 27192089 TI - Aqueous Photochemistry of Glyoxylic Acid. AB - Aerosols affect climate change, the energy balance of the atmosphere, and public health due to their variable chemical composition, size, and shape. While the formation of secondary organic aerosols (SOA) from gas phase precursors is relatively well understood, studying aqueous chemical reactions contributing to the total SOA budget is the current focus of major attention. Field measurements have revealed that mono-, di-, and oxo-carboxylic acids are abundant species present in SOA and atmospheric waters. This work explores the fate of one of these 2-oxocarboxylic acids, glyoxylic acid, which can photogenerate reactive species under solar irradiation. Additionally, the dark thermal aging of photoproducts is studied by UV-visible and fluorescence spectroscopies to reveal that the optical properties are altered by the glyoxal produced. The optical properties display periodicity in the time domain of the UV-visible spectrum of chromophores with absorption enhancement (thermochromism) or loss (photobleaching) during nighttime and daytime cycles, respectively. During irradiation, excited state glyoxylic acid can undergo alpha-cleavage or participate in hydrogen abstractions. The use of (13)C nuclear magnetic resonance spectroscopy (NMR) analysis shows that glyoxal is an important intermediate produced during direct photolysis. Glyoxal quickly reaches a quasi-steady state as confirmed by UHPLC-MS analysis of its corresponding (E) and (Z) 2,4 dinitrophenylhydrazones. The homolytic cleavage of glyoxylic acid is proposed as a fundamental step for the production of glyoxal. Both carbon oxides, CO2(g) and CO(g) evolving to the gas-phase, are quantified by FTIR spectroscopy. Finally, formic acid, oxalic acid, and tartaric acid photoproducts are identified by ion chromatography (IC) with conductivity and electrospray (ESI) mass spectrometry (MS) detection and (1)H NMR spectroscopy. A reaction mechanism is proposed based on all experimental observations. PMID- 27192088 TI - The phenomenon of fluorescence in immunosensors. AB - The phenomenon of fluorescence in immunosensors is described in this paper. Both structure and characteristics of biosensors and immunosensors are presented. Types of immunosensors and the response of bioreceptor layers to the reaction with analytes as well as measurements of electrochemical, piezoelectric and optical parameters in immunosensors are also presented. In addition, detection techniques used in studies of optical immunosensors based on light-matter interactions (absorbance, reflectance, dispersion, emission) such as: UV/VIS spectroscopy, reflectometric interference spectroscopy (RIfs), surface plasmon resonance (SPR), optical waveguide light-mode spectroscopy (OWLS), fluorescence spectroscopy. The phenomenon of fluorescence in immunosensors and standard configurations of immunoreactions between an antigen and an antibody (direct, competitive, sandwich, displacement) is described. Fluorescence parameters taken into account in analyses and fluorescence detection techniques used in research of immunosensors are presented. Examples of immunosensor applications are given. PMID- 27192090 TI - The impact of supervised weight loss and intentional weight regain on sex hormone binding globulin and testosterone in premenopausal women. AB - What is the impact of intentional weight loss and regain on serum androgens in women? We conducted an ancillary analysis of prospectively collected samples from a randomized controlled trial. The trial involved supervised 10% weight loss (8.5 kg on average) with diet and exercise over 4-6 months followed by supervised intentional regain of 50% of the lost weight (4.6 kg on average) over 4-6 months. Participants were randomized prior to the partial weight regain component to either continuation or cessation of endurance exercise. Analytic sample included 30 obese premenopausal women (mean age of 40 +/- 5.9 years, mean baseline body mass index (BMI) of 32.9 +/- 4.2 kg/m(2)) with metabolic syndrome. We evaluated sex hormone binding globulin (SHBG), total testosterone (T), free androgen index (FAI), and high molecular weight adiponectin (HMWAdp). Insulin, homeostasis model assessment (HOMA), and quantitative insulin sensitivity check index (QUICKI), and visceral adipose tissue (VAT) measured in the original trial were reanalyzed for the current analytic sample. Insulin, HOMA, and QUICKI improved with weight loss and were maintained despite weight regain. Log-transformed SHBG significantly increased from baseline to weight loss, and then significantly decreased with weight regain. LogFAI and logVAT decreased similarly and increased with weight loss followed by weight regain. No changes were found in logT and LogHMWAdp. There was no significant difference in any tested parameters by exercise between the groups. SHBG showed prominent sensitivity to body mass fluctuations, as reduction with controlled intentional weight regain showed an inverse relationship to VAT and occurred despite stable HMWAdp and sustained improvements with insulin resistance. FAI showed opposite changes to SHBG, while T did not change significantly with weight. Continued exercise during weight regain did not appear to impact these findings. PMID- 27192091 TI - False Balance in Public Health Reporting? Michele Bachmann, the HPV Vaccine, and "Mental Retardation". AB - This content analysis of media coverage of Michele Bachmann's erroneous comments that the HPV vaccine causes mental retardation explores the relationship between truth-telling (the presentation of accurate information) and balance (presenting opposing perspectives of an issue equally and legitimately) in public health reporting. Of 200 articles analyzed, about 50% provided correction and about 40% provided a counterpoint. We also found that health reporters tended to engage in truth-telling and balance more than political reporters. Implications for theory and practice are discussed. PMID- 27192086 TI - Susceptibility-weighted imaging: current status and future directions. AB - Susceptibility-weighted imaging (SWI) is a method that uses the intrinsic nature of local magnetic fields to enhance image contrast in order to improve the visibility of various susceptibility sources and to facilitate diagnostic interpretation. It is also the precursor to the concept of the use of phase for quantitative susceptibility mapping (QSM). Nowadays, SWI has become a widely used clinical tool to image deoxyhemoglobin in veins, iron deposition in the brain, hemorrhages, microbleeds and calcification. In this article, we review the basics of SWI, including data acquisition, data reconstruction and post-processing. In particular, the source of cusp artifacts in phase images is investigated in detail and an improved multi-channel phase data combination algorithm is provided. In addition, we show a few clinical applications of SWI for the imaging of stroke, traumatic brain injury, carotid vessel wall, siderotic nodules in cirrhotic liver, prostate cancer, prostatic calcification, spinal cord injury and intervertebral disc degeneration. As the clinical applications of SWI continue to expand both in and outside the brain, the improvement of SWI in conjunction with QSM is an important future direction of this technology. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27192092 TI - Azathioprine and 6-mercaptopurine for maintenance of remission in ulcerative colitis. AB - BACKGROUND: Maintenance of remission is a major issue in inflammatory bowel disease. In ulcerative colitis, the evidence for the effectiveness of azathioprine and 6-mercaptopurine for the maintenance of remission is still controversial. OBJECTIVES: To assess the effectiveness and safety of azathioprine and 6-mercaptopurine for maintaining remission of ulcerative colitis. SEARCH METHODS: The MEDLINE, EMBASE and Cochrane Library databases were searched from inception to 30 July 2015. Both full randomized controlled trials and associated abstracts were included. SELECTION CRITERIA: Randomized controlled trials of at least 12 months duration that compared azathioprine or 6-mercaptopurine with placebo or standard maintenance therapy (e.g. mesalazine) were included. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data using standard forms. Disagreements were solved by consensus including a third author. Study quality was assessed using the Cochrane risk of bias tool. The primary outcome was failure to maintain clinical or endoscopic remission. Secondary outcomes included adverse events and withdrawal due to adverse events. Analyses were performed separately by type of control (placebo, or active comparator). Pooled risk ratios were calculated based on the fixed-effect model unless heterogeneity was shown. The GRADE approach was used to assess the overall quality of evidence for pooled outcomes. MAIN RESULTS: Seven studies including 302 patients with ulcerative colitis were included in the review. The risk of bias was high in three of the studies due to lack of blinding. Azathioprine was shown to be significantly superior to placebo for maintenance of remission. Fourty-four per cent (51/115) of azathioprine patients failed to maintain remission compared to 65% (76/117) of placebo patients (4 studies, 232 patients; RR 0.68, 95% CI 0.54 to 0.86). A GRADE analysis rated the overall quality of the evidence for this outcome as low due to risk of bias and imprecision (sparse data). Two trials that compared 6-mercaptopurine to mesalazine, or azathioprine to sulfasalazine showed significant heterogeneity and thus were not pooled. Fifty per cent (7/14) of 6 mercaptopurine patients failed to maintain remission compared to 100% (8/8) of mesalazine patients (1 study, 22 patients; RR 0.53, 95% CI 0.31 to 0.90). Fifty eight per cent (7/12) of azathioprine patients failed to maintain remission compared to 38% (5/13) of sulfasalazine patients (1 study, 25 patients; RR 1.52, 95% CI 0.66 to 3.50). One small study found that 6-mercaptopurine was superior to methotrexate for maintenance of remission. In the study, 50% (7/14) of 6 mercaptopurine patients and 92% (11/12) of methotrexate patients failed to maintain remission (1 study, 26 patients; RR 0.55, 95% CI 0.31 to 0.95). One very small study compared azathioprine with cyclosporin and found that there was no significant difference between patients failing remission on azathioprine (50%, 4/8) or cyclosporin (62.5%, 5/8) (1 study, 16 patients, RR 0.80 95% CI 0.33 to 1.92). When placebo-controlled studies were pooled with aminosalicylate comparator studies to assess adverse events, there was no statistically significant difference between azathioprine and control in the incidence of adverse events. Nine per cent (11/127) of azathioprine patients experienced at least one adverse event compared to 2% (3/130) of placebo patients (5 studies, 257 patients; RR 2.82, 95% CI 0.99 to 8.01). Patients receiving azathioprine were at significantly increased risk of withdrawing due to adverse events. Eight per cent (8/101) of azathioprine patients withdrew due to adverse events compared to 0% (0/98) of control patients (5 studies, 199 patients; RR 5.43, 95% CI 1.02 to 28.75). Adverse events related to study medication included acute pancreatitis (3 cases, plus 1 case on cyclosporin) and significant bone marrow suppression (5 cases). Deaths, opportunistic infection or neoplasia were not reported. AUTHORS' CONCLUSIONS: Azathioprine therapy appears to be more effective than placebo for maintenance of remission in ulcerative colitis. Azathioprine or 6-mercaptopurine may be effective as maintenance therapy for patients who have failed or cannot tolerate mesalazine or sulfasalazine and for patients who require repeated courses of steroids. More research is needed to evaluate superiority over standard maintenance therapy, especially in the light of a potential for adverse events from azathioprine. This review updates the existing review of azathioprine and 6-mercaptopurine for maintenance of remission in ulcerative colitis which was published in the Cochrane Library (September 2012). PMID- 27192093 TI - Validation of calculation algorithms for organ doses in CT by measurements on a 5 year old paediatric phantom. AB - Many organ dose calculation tools for computed tomography (CT) scans rely on the assumptions: (1) organ doses estimated for one CT scanner can be converted into organ doses for another CT scanner using the ratio of the Computed Tomography Dose Index (CTDI) between two CT scanners; and (2) helical scans can be approximated as the summation of axial slices covering the same scan range. The current study aims to validate experimentally these two assumptions. We performed organ dose measurements in a 5 year-old physical anthropomorphic phantom for five different CT scanners from four manufacturers. Absorbed doses to 22 organs were measured using thermoluminescent dosimeters for head-to-torso scans. We then compared the measured organ doses with the values calculated from the National Cancer Institute dosimetry system for CT (NCICT) computer program, developed at the National Cancer Institute. Whereas the measured organ doses showed significant variability (coefficient of variation (CoV) up to 53% at 80 kV) across different scanner models, the CoV of organ doses normalised to CTDIvol substantially decreased (12% CoV on average at 80 kV). For most organs, the difference between measured and simulated organ doses was within +/-20% except for the bone marrow, breasts and ovaries. The discrepancies were further explained by additional Monte Carlo calculations of organ doses using a voxel phantom developed from CT images of the physical phantom. The results demonstrate that organ doses calculated for one CT scanner can be used to assess organ doses from other CT scanners with 20% uncertainty (k = 1), for the scan settings considered in the study. PMID- 27192094 TI - Addiction and crime: The importance of asymmetry in offending and the life course. AB - The intersection of addiction and crime is pervasive. Not only is there a high prevalence of substance use and substance use disorders among criminal justice populations that is substantially higher than in the general population, but also offenders with substance use disorders are more likely to be rearrested. The authors believe there are several broad points that addiction researchers and criminologists have come to understand that are important to bring together. In this commentary, the asymmetrical nature of crime (i.e., a small subset account for the lion's share of offending) and the value of a developmentally sensitive life-course approach to inform criminal behavior are elucidated and discussed. These 2 themes are intertwined. High-impact offenders have extensive drug use histories and need intervention (policy or individual-level), but the form and content and ultimately the effectiveness of the intervention may depend on what period in the life-course the intervention is to be implemented. PMID- 27192095 TI - A Case of Immunoglobulin G4-associated Anterior Uveitis and Remitting Seronegative Symmetrical Synovitis with Pitting Edema Syndrome. PMID- 27192098 TI - Novel Avian Influenza A(H5N8) Viruses in Migratory Birds, China, 2013-2014. PMID- 27192097 TI - High MICs for Vancomycin and Daptomycin and Complicated Catheter-Related Bloodstream Infections with Methicillin-Sensitive Staphylococcus aureus. AB - We investigated the prognostic role of high MICs for antistaphylococcal agents in patients with methicillin-sensitive Staphylococcus aureus catheter-related bloodstream infection (MSSA CRBSI). We prospectively reviewed 83 episodes from 5 centers in Spain during April 2011-June 2014 that had optimized clinical management and analyzed the relationship between E-test MICs for vancomycin, daptomycin, oxacillin, and linezolid and development of complicated bacteremia by using multivariate analysis. Complicated MSSA CRBSI occurred in 26 (31.3%) patients; MICs for vancomycin and daptomycin were higher in these patients (optimal cutoff values for predictive accuracy = 1.5 MUg/mL and 0.5 MUg/mL). High MICs for vancomycin (hazard ratio 2.4, 95% CI 1.2-5.5) and daptomycin (hazard ratio 2.4, 95% CI 1.1-5.9) were independent risk factors for development of complicated MSSA CRBSI. Our data suggest that patients with MSSA CRBSI caused by strains that have high MICs for vancomycin or daptomycin are at increased risk for complications. PMID- 27192096 TI - Disc cell senescence in intervertebral disc degeneration: Causes and molecular pathways. AB - The accumulation of senescent disc cells in degenerative intervertebral disc (IVD) suggests the detrimental roles of cell senescence in the pathogenesis of intervertebral disc degeneration (IDD). Disc cell senescence decreased the number of functional cells in IVD. Moreover, the senescent disc cells were supposed to accelerate the process of IDD via their aberrant paracrine effects by which senescent cells cause the senescence of neighboring cells and enhance the matrix catabolism and inflammation in IVD. Thus, anti-senescence has been proposed as a novel therapeutic target for IDD. However, the development of anti-senescence therapy is based on our understanding of the molecular mechanism of disc cell senescence. In this review, we focused on the molecular mechanism of disc cell senescence, including the causes and various molecular pathways. We found that, during the process of IDD, age-related damages together with degenerative external stimuli activated both p53-p21-Rb and p16-Rb pathways to induce disc cell senescence. Meanwhile, disc cell senescence was regulated by multiple signaling pathways, suggesting the complex regulating network of disc cell senescence. To understand the mechanism of disc cell senescence better contributes to developing the anti-senescence-based therapies for IDD. PMID- 27192099 TI - Passive Anti-Icing and Active Deicing Films. AB - Anti-icing and deicing are the two major pathways for suppressing adhesion of ice on surfaces, yet materials with dual capabilities are rare. In this work, we have designed a perfluorododecylated graphene nanoribbon (FDO-GNR) film that takes advantage of both the low polarizability of perfluorinated carbons and the intrinsic conductive nature of graphene nanoribbons. The FDO-GNR films are superhydrophobic with a sheet resistance below 8 kOmega.sq(-1) and then exhibit an anti-icing property that prevents freezing of incoming ice-cold water down to 14 degrees C. After that point, voltage can be applied to the films to resistively heat and deice the surface. Further a lubricating liquid can be employed to create a slippery surface to improve the film's deicing performance. The FDO-GNR films can be easily switched between the superhydrophobic anti-icing mode and the slippery deicing mode by applying the lubricant. A spray-coating method makes it suitable for large-scale applications. The anti-icing and deicing properties render the FDO-GNR films with promise for use in extreme environments. PMID- 27192101 TI - Surgical Management of Double-Head Pterygium Using a Modified Split-Conjunctival Autograft Technique. AB - AIM: To describe a modified split-conjuctival autograft technique for double-head pterygium and evaluate the postoperative outcomes. METHODS: A retrospective analysis of all patients who underwent split-conjunctival autograft surgery for double-head pterygium from November 2012 to March 2014. Conjunctival autograft was split vertically, in order to obtain limbal sides of cojunctival autograft for both sides. No adjunctive agent was used. Records of included patients were reviewed and outcomes and recurrence rates were noted. RESULTS: Eight cases of double-head pterygia were noted in 158 total cases of pterygia evaluated (5%). The baseline characteristics included 2 female and 6 male with an age between 26 and 71 (average 42.63) years. All eyes had 12-month follow-ups in average (6-21 months). No intraoperative or postoperative complications were noted. No recurrence was observed. CONCLUSION: A modified, vertical-split conjunctival autograft without any adjunctive agents is a successful and safe technique in management of double-head pterygium. PMID- 27192100 TI - Comprehensive Assessment of Factors Associated With In-Hospital Mortality After Elective Abdominal Aortic Aneurysm Repair. AB - IMPORTANCE: Patient- and hospital-level factors affecting outcomes after open and endovascular abdominal aortic aneurysm (AAA) repair are each well described separately, but not together. OBJECTIVE: To describe the association of patient- and hospital-level factors with in-hospital mortality after elective AAA repair. DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of the Nationwide Inpatient Sample database (January 2007-December 2011). The review included all patients undergoing elective open AAA repair (OAR) or endovascular AAA repair (EVAR) and was conducted between December 2014 and January 2015. MAIN OUTCOMES AND MEASURES: Factors associated with in-hospital mortality were analyzed for OAR and EVAR using multivariable analyses, adjusting for previously defined patient- and hospital-level risk factors. RESULTS: Of the 166 443 surgeries (131 908 EVARs and 34 535 OARs) that were performed at 1207 hospitals, 133 407 patients (80.2%) were men, 123 522 patients (89.6%) were white, and the mean (SD) age was 73 (0.04) years. Overall in-hospital mortality was 0.7% for EVAR and 3.8% for OAR. Mortality after EVAR was significantly higher among hospitals with high general surgery mortality (mortality quartile >= 50%; odds ratio [OR], 1.37; 95% CI, 1.01 1.86; P = .04) and there was no difference in mortality among hospitals meeting the Leapfrog criteria for AAA repair (OR, 0.64; 95% CI, 0.38-1.09; P = .09). Mortality after OAR was significantly lower among hospitals performing at least 25% of AAA repairs using open techniques (OR, 0.68; 95% CI, 0.52-0.88; P = .004). Neither hospital bed size nor teaching status was significantly associated with mortality after either EVAR or OAR. Overall, OAR (OR, 6.07; 95% CI, 4.92-7.49) and intrinsic patient risk (Medicare score; OR, 4.81; 95% CI, 3.45-6.72) were most likely associated with in-hospital mortality after AAA repair, although hospitals with poor general surgery performance (OR, 1.31; 95% CI, 1.06-1.63) and those with at least a 25% proportion of open cases (OR, 1.39; 95% CI, 1.10-1.75) were also significantly associated with mortality (all P < .002). Notably, the proportion of institutions performing at least 25% open cases fell from 41% in 2007 to 18% in 2011 (P < .001). CONCLUSIONS AND RELEVANCE: Patient-level factors were associated with in-hospital mortality outcomes after elective AAA repair. Hospital case volume and practice patterns were also associated. This demonstrates the importance of adequate institutional experience with OAR techniques, which appear to be critically declining. Based on these data, appropriate patient selection and medical optimization appear to be the most important means by which we can improve outcomes following elective AAA repair, although patient referral to high-volume aortic centers of excellence should be a secondary consideration. PMID- 27192102 TI - A role for private sector laboratories in public health surveillance of antimicrobial resistance. PMID- 27192103 TI - Evaluation of flow injection analysis method with spectrophotometric detection for the determination of atrazine in soil extracts. AB - A method for determining atrazine in soil extracts was evaluated by flow injection analysis with spectrophotometric detection. The method is based on the reaction of atrazine with pyridine in an acid medium followed by the reaction with NaOH and sulfanilic acid. Several analytical conditions were previously studied and optimized. Under the best conditions of analysis, the limits of detection and quantification were 0.15 and 0.45 mg L(-1), respectively, for a linear response between 0.50 and 2.50 mg L(-1), and a sampling throughput of 21 determinations per hour. Using the standard addition method, the maximum relative standard deviation of 17% and recovery values between 80 and 100% were observed for three extracts from soil samples with different composition. The proposed method is simple, low-cost and easy to use, and can be employed for studies involving atrazine in soil samples or for screening of atrazine in soils. PMID- 27192104 TI - Naphthotetrathiophene-Based Helicene-Like Molecules: Synthesis and Photophysical Properties. AB - Two novel helicene-like molecules based on naphthotetrathiophene are successfully synthesized. All target molecules and intermediates are characterized by (1)H NMR, (13)C NMR, IR, and HRMS. Their electrochemical and photophysical properties are studied. The configurations of the molecules are optimized by DFT quantum calculations and UV-vis behaviors are also predicted to further understand the origin of different absorption bands. We believe the current work illustrated an efficient way for the design and synthesis of sophisticated structures with naphthotetrathiophene as building blocks. PMID- 27192107 TI - Utilite De La gamma Glutamyl Transpeptidase De La 5'Nucleotidase Et Des Isozymes De La Phosphatase Alcaline Pour Le Diagnostic Differentiel Des Affectations Hepatiques. AB - The use of the determination of the gamma-glutamyl-transpeptidase (GT), the 5'nucleotidase and of the isoenzymes of the alkaline phosphatase for the differential diagnoses of liver disease is discussed. It is concluded that the GT is a useful test to diagnose diseases of liver, common bile duct or pancreas, but without distinction between these illnessess. An affection of these organs is not very probable if the GT is normal, it is very probable if the level of activity exceeds 500 units. In cancer patients without jaundice, a normal level of this enzyme suggests the absence of metastases of the liver. The enzymatic activity is normal in case of bone affection but can be elevated in case of some neurological diseases and 3 to 4 days after the beginning of a myocardial infarction. An abnormally elevated 5'nucleotidase accompanied with an elevated alkaline phosphatase suggests strongly the presence of an hepatobiliary damage, except when the alkaline phosphatase is very elevated, which may cause an "apparent" increase of the 5'nucleotidase and except when the elevation is due to a bone damage. The rise in case of bone damage seems however not to take place by more than 10 % of the cases. This enzyme is also useful for the diagnoses of active chronic liver damages. The determination of the isoenzymes of the alkaline phosphatase seems especially useful in case of an increase of the phosphatase alkaline whilst the 5'nucleotidase and the liver tests are normal. It often gives the possibility to determine whether the increase of the alkaline phosphatase in that case can be ascribed to a bone or to a liver damage. The technical details are important. The electrophoresis on acrylamide and the inactivation by heat seem to be adequate methods. To the autors it appears that the determination of the GT and of the 5'nucleotidase can find place in the classical liver tests, from one could eliminate other tests such as the Hanger. As far as the determination of the isoenzymes of the alkaline phosphatase is concerned, their application could be reserved for selected cases. PMID- 27192106 TI - Avant Propos. PMID- 27192105 TI - Aerobic Copper-Mediated Domino Three-Component Approach to 2-Aminobenzothiazole Derivatives. AB - An unprecedented three-component reaction involving a 2,2'-diaminodiaryl disulfide, copper cyanide, and an electrophile is described. This transformation is based on an oxidative copper-mediated S-cyanation as a key step and involves a cyanation/cyclization/acylation domino sequence enabling a rapid and efficient synthesis of diversely substituted 2-aminobenzothiazole derivatives. Notably, this reaction proceeds via an original mechanism involving an intermolecular migration of the acyl group. PMID- 27192108 TI - Electroforese Van Lactaatdehydrogenase-Isoenzymen Op Hypergelcelluloseacetaat. AB - Hypergel cellulose acetate is an excellent medium for LDH-isoenzymes electrophoresis because of its high degree of gellation. The cellulose acetate is brought on a polyester sheet which makes it much easier to handle throughout the electrophoresis and coloration procedures. For coloration of the isoenzymes, the generally used techniques are applicable. PMID- 27192109 TI - Which Way In The Labyrinth Of The Newer Penicillins ? PMID- 27192110 TI - Selected Summaries. PMID- 27192112 TI - Protein-RNA Dynamics in the Central Junction Control 30S Ribosome Assembly. AB - Interactions between ribosomal proteins (rproteins) and ribosomal RNA (rRNA) facilitate the formation of functional ribosomes. S15 is a central domain primary binding protein that has been shown to trigger a cascade of conformational changes in 16S rRNA, forming the functional structure of the central domain. Previous biochemical and structural studies in vitro have revealed that S15 binds a three-way junction of helices 20, 21, and 22, including nucleotides 652-654 and 752-754. All junction nucleotides except 653 are highly conserved among the Bacteria. To identify functionally important motifs within the junction, we subjected nucleotides 652-654 and 752-754 to saturation mutagenesis and selected and analyzed functional mutants. Only 64 mutants with greater than 10% ribosome function in vivo were isolated. S15 overexpression complemented mutations in the junction loop in each of the partially active mutants, although mutations that produced inactive ribosomes were not complemented by overexpression of S15. Single-molecule Forster or fluorescence resonance energy transfer (smFRET) was used to study the Mg(2+)- and S15-induced conformational dynamics of selected junction mutants. Comparison of the structural dynamics of these mutants with the wild type in the presence and absence of S15 revealed specific sequence and structural motifs in the central junction that are important in ribosome function. PMID- 27192113 TI - Adult Children of Parents with Mental Illness: Losing Oneself. Who am I? AB - There is a limited body of research that focuses on experiences of families of people with mental illness. While the body of knowledge concerning children of parents with mental illness is increasing, there remains limited discourse surrounding the experiences of adults who have lived with childhood parental mental illness. This paper examined one major theme of a study focusing on parenting narratives of adults who had experienced childhood parental mental illness. The narrative study from a metropolitan area of Australia reflects adult children's experiences of being overwhelmed with parental mental illness. They felt unsure of their own emotions and felt they had lost a sense of who they were as individual people. Adult children felt confused about their sense of reality, particularly for those whose parent had a diagnosis of schizophrenia or psychosis. Their experiences of loss were closely associated with changing self identity. Furthermore, many of the narratives demonstrated experiences of grief for adult children. Greater understanding of adult children's perceptions of being parented by a person with mental illness, alongside their experiences of loss, has the potential to help health and social care professionals to facilitate greater resilience for families who are living with parental mental illness. PMID- 27192114 TI - Management of cardiovascular disease in patients with psoriasis. AB - INTRODUCTION: Patients with psoriasis have an increased incidence and prevalence of cardiovascular (CV) risk factors, and CV undertreatment in these patients is a well-established problem. The link between psoriasis and CV disease is present on a pathogenic level, as well as due to modifiable lifestyle factors such as smoking and alcohol abuse. AREAS COVERED: In this manuscript we describe the evidence associating psoriasis with CV disease, as well as the pharmacological and non-pharmacological treatment of CV risk factors including the CV effects of anti-psoriatic therapy and vice versa. EXPERT OPINION: Current guidelines recommend that patients with psoriasis are screened for CV risk factors, and recommend smoking cessation, reduced alcohol consumption, altering of lifestyle to move to a normal-weight body-mass index, exercising 3 times a week for 30 minutes, and monitoring and modifying cholesterol levels, respectively. While the current sum of evidence is not sufficient to recommend specific therapies for psoriasis solely based on their potential CV impact, some guidelines have suggested a 1.5 multiplication factor, in patients with severe psoriasis, to the Framingham risk score. Indeed, the importance of screening for CV risk factors and strict adherence to established primary and secondary preventive measures in these patients should be emphasized. PMID- 27192115 TI - WDR5 high expression and its effect on tumorigenesis in leukemia. AB - WD repeat domain 5 (WDR5) plays an important role in various biological functions through the epigenetic regulation of gene transcription. However, the oncogenic effect of WDR5 in leukemia remains largely unknown. Here, we found WDR5 expression is increased in leukemia patients. High expression of WDR5 is associated with high risk leukemia; Patients with WDR5 and MLL1 high expression have poor complete remission rate. We further identified the global genomic binding of WDR5 in leukemic cells and found the genomic co-localization of WDR5 binding with H3K4me3 enrichment. Moreover, WDR5 knockdown by shRNA suppresses cell proliferation, induces apoptosis, inhibits the expression of WDR5 targets, and blocks the H3K4me3 enrichment on the promoter of its targets. We also observed the positive correlation of WDR5 expression with these targets in the cohort study of leukemia patients. Our data reveal that WDR5 may have oncogenic effect and WDR5-mediated H3K4 methylation plays an important role in leukemogenesis. PMID- 27192117 TI - Differential DNA methylation patterns of polycystic ovarian syndrome in whole blood of Chinese women. AB - As a universally common endocrinopathy in women of reproductive age, the polycystic ovarian syndrome is characterized by composite clinical phenotypes reflecting the contributions of reproductive impact of ovarian dysfunction and metabolic abnormalities with widely varying symptoms resulting from interference of the genome with the environment through integrative biological mechanisms including epigenetics. We have performed a genome-wide DNA methylation analysis on polycystic ovarian syndrome and identified a substantial number of genomic sites differentially methylated in the whole blood of PCOS patients and healthy controls (52 sites, false discovery rate < 0.05 and corresponding p value < 5.68e 06), highly consistently replicating biological pathways extensively implicated in immunity and immunity-related inflammatory disorders (false discovery rate < 0.05) that were reportedly regulated in the DNA methylome from ovarian tissue under PCOS condition. Most importantly, our genome-wide profiling focusing on PCOS patients revealed a large number of DNA methylation sites and their enriched functional pathways significantly associated with diverse clinical features (levels of prolactin, estradiol, progesterone and menstrual cycle) that could serve as novel molecular basis of the clinical heterogeneity observed in PCOS women. PMID- 27192116 TI - The IDO1 selective inhibitor epacadostat enhances dendritic cell immunogenicity and lytic ability of tumor antigen-specific T cells. AB - Epacadostat is a novel inhibitor of indoleamine-2,3-dioxygenase-1 (IDO1) that suppresses systemic tryptophan catabolism and is currently being evaluated in ongoing clinical trials. We investigated the effects of epacadostat on (a) human dendritic cells (DCs) with respect to maturation and ability to activate human tumor antigen-specific cytotoxic T-cell (CTL) lines, and subsequent T-cell lysis of tumor cells, (b) human regulatory T cells (Tregs), and (c) human peripheral blood mononuclear cells (PBMCs) in vitro. Simultaneous treatment with epacadostat and IFN-gamma plus lipopolysaccharide (LPS) did not change the phenotype of matured human DCs, and as expected decreased the tryptophan breakdown and kynurenine production. Peptide-specific T-cell lines stimulated with DCs pulsed with peptide produced significantly more IFN-gamma, TNFalpha, GM-CSF and IL-8 if the DCs were treated with epacadostat. These T cells also displayed higher levels of tumor cell lysis on a per cell basis. Epacadostat also significantly decreased Treg proliferation induced by IDO production from IFN-gamma plus LPS matured human DCs, although the Treg phenotype did not change. Multicolor flow cytometry was performed on human PBMCs treated with epacadostat; analysis of 123 discrete immune cell subsets revealed no changes in major immune cell types, an increase in activated CD83+ conventional DCs, and a decrease in immature activated Tim3+ NK cells. These studies show for the first time several effects of epacadostat on human DCs, and subsequent effects on CTL and Tregs, and provide a rationale as to how epacadostat could potentially increase the efficacy of immunotherapeutics, including cancer vaccines. PMID- 27192119 TI - dbCPG: A web resource for cancer predisposition genes. AB - Cancer predisposition genes (CPGs) are genes in which inherited mutations confer highly or moderately increased risks of developing cancer. Identification of these genes and understanding the biological mechanisms that underlie them is crucial for the prevention, early diagnosis, and optimized management of cancer. Over the past decades, great efforts have been made to identify CPGs through multiple strategies. However, information on these CPGs and their molecular functions is scattered. To address this issue and provide a comprehensive resource for researchers, we developed the Cancer Predisposition Gene Database (dbCPG, Database URL: http://bioinfo.ahu.edu.cn:8080/dbCPG/index.jsp), the first literature-based gene resource for exploring human CPGs. It contains 827 human (724 protein-coding, 23 non-coding, and 80 unknown type genes), 637 rats, and 658 mouse CPGs. Furthermore, data mining was performed to gain insights into the understanding of the CPGs data, including functional annotation, gene prioritization, network analysis of prioritized genes and overlap analysis across multiple cancer types. A user-friendly web interface with multiple browse, search, and upload functions was also developed to facilitate access to the latest information on CPGs. Taken together, the dbCPG database provides a comprehensive data resource for further studies of cancer predisposition genes. PMID- 27192118 TI - Fibroblast growth factor receptor 4 (FGFR4) and fibroblast growth factor 19 (FGF19) autocrine enhance breast cancer cells survival. AB - Basal-like breast cancer is an aggressive tumor subtype with poor prognosis. The discovery of underlying mechanisms mediating tumor cell survival, and the development of novel agents to target these pathways, is a priority for patients with basal-like breast cancer. From a functional screen to identify key drivers of basal-like breast cancer cell growth, we identified fibroblast growth factor receptor 4 (FGFR4) as a potential mediator of cell survival. We found that FGFR4 mediates cancer cell survival predominantly via activation of PI3K/AKT. Importantly, a subset of basal-like breast cancer cells also secrete fibroblast growth factor 19 (FGF19), a canonical ligand specific for FGFR4. siRNA-mediated silencing of FGF19 or neutralization of extracellular FGF19 by anti-FGF19 antibody (1A6) decreases AKT phosphorylation, suppresses cancer cell growth and enhances doxorubicin sensitivity only in the FGFR4+/FGF19+ breast cancer cells. Consistently, FGFR4/FGF19 co-expression was also observed in 82 out of 287 (28.6%) primary breast tumors, and their expression is strongly associated with AKT phosphorylation, Ki-67 staining, higher tumor stage and basal-like phenotype. In summary, our results demonstrated the presence of an FGFR4/FGF19 autocrine signaling that mediates the survival of a subset of basal-like breast cancer cells and suggest that inactivation of this autocrine loop may potentially serve as a novel therapeutic intervention for future treatment of breast cancers. PMID- 27192122 TI - Visible/near-IR-light-driven TNFePc/BiOCl organic-inorganic heterostructures with enhanced photocatalytic activity. AB - Although semiconductor photocatalysis has been reported for more than 40 years, the spectral response is still focused on the region of UV-Visible and it is seldom extended to more than 600 nm. In this work, visible/near-IR-light-driven 2,9,16,23-tetranitrophthalocyanine iron (FeTNPc)/bismuth oxychloride (BiOCl) organic-inorganic heterostructures have been synthesized by a two-step solvothermal method. The obtained products were characterized by X-ray diffraction, Fourier transform infrared spectra, scanning electron and transmission microscopy, energy dispersive X-ray spectrometer, UV-vis diffuse reflectance spectroscopy, nitrogen adsorption-desorption, and electrochemical measurements. The photocatalytic activity for the decomposition of methyl orange and bisphenol A solution can be significantly improved under visible/near-IR light irradiation. Through detecting the main oxidative species by trapping experiments, the results show holes and O2(-) radicals are majorly and minorly responsible for photodegradation respectively. What's more, the FeTNPc/BiOCl composite photocatalyst still retained the photocatalytic activity after three cycle measurements. PMID- 27192120 TI - Telomerase inhibitor imetelstat has preclinical activity across the spectrum of non-small cell lung cancer oncogenotypes in a telomere length dependent manner. AB - Telomerase was evaluated as a therapeutic oncotarget by studying the efficacy of the telomerase inhibitor imetelstat in non-small cell lung cancer (NSCLC) cell lines to determine the range of response phenotypes and identify potential biomarkers of response. A panel of 63 NSCLC cell lines was studied for telomere length and imetelstat efficacy in inhibiting colony formation and no correlation was found with patient characteristics, tumor histology, and oncogenotypes. While there was no overall correlation between imetelstat efficacy with initial telomere length (ranging from 1.5 to 20 kb), the quartile of NSCLC lines with the shortest telomeres was more sensitive than the quartile with the longest telomeres. Continuous long-term treatment with imetelstat resulted in sustained telomerase inhibition, progressive telomere shortening and eventual growth inhibition in a telomere-length dependent manner. Cessation of imetelstat therapy before growth inhibition was followed by telomere regrowth. Likewise, in vivo imetelstat treatment caused tumor xenograft growth inhibition in a telomere length dependent manner. We conclude from these preclinical studies of telomerase as an oncotarget tested by imetelstat response that imetelstat has efficacy across the entire oncogenotype spectrum of NSCLC, continuous therapy is necessary to prevent telomere regrowth, and short telomeres appears to be the best treatment biomarker. PMID- 27192121 TI - LncRNA-RMRP promotes carcinogenesis by acting as a miR-206 sponge and is used as a novel biomarker for gastric cancer. AB - Long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis. However, the mechanisms of most lncRNAs in cancers are largely unknown. Because the RNA component of mitochondrial RNA processing endoribonuclease (RMRP) is one of the dysregulated lncRNAs in gastric cancer, this study explored its molecular mechanisms in carcinogenesis. RMRP levels in 792 tissues, plasma and gastric juices from patients with various stages of gastric tumorigenesis were analyzed by quantitative reverse transcription-polymerase chain reaction. Overexpression and RNA interference were used to manipulate RMRP expression by RMRP expression vector and small interfering RNAs, respectively. Its mechanisms were evaluated by flow cytometry, real-time cell analysis, plate colony formation assays, and xenograft models. RMRP levels in tissue, plasma and gastric juices from patients with gastric cancer were significantly different from those from controls. Its levels were significantly associated with Borrmann type and metastasis. Plasma and gastric juice RMRP had higher sensitivity and specificity than commonly used markers (such as carcinoembryonic antigen and carbohydrate antigen 19-9). Knockdown of RMRP significantly inhibited cell proliferation in vitro and in vivo, whereas overexpression of RMRP promoted cell growth. Acting as a miR-206 sponge, RMRP modulated cell cycle by regulating Cyclin D2 expression. RMRP plays a crucial role in gastric cancer occurrence and can be used as a novel biomarker for gastric cancer. PMID- 27192123 TI - African American race associated with body image dissatisfaction among patients with systemic sclerosis. AB - OBJECTIVES: Studies have shown a high degree of body image dissatisfaction among patients with systemic sclerosis (SSc). We aimed to identify demographic and phenotypic characteristics that correlate with body image dissatisfaction. METHODS: Ninety-eight patients with SSc were recruited from Georgetown University Medical Center 2003-2004. Anonymous surveys collected demographic information (age, race, gender, duration/type of SSc) and assessed degree of body image dissatisfaction on a scale of 0-3 in relation to phenotypic features of SSc (hand contractures, finger ulcers, pigmentation changes, lip wrinkling/thinning, telangiectasias). A composite total distress score was derived. Parametric and nonparametric T tests were used to compare groups. RESULTS: Of 98 patients, 86 were female and 12 male. The majority of patients were 30-60 years old. The sample was 62% Caucasian, 27% African American, and the rest identified as "other". Twenty-seven percent had limited SSc, 48% diffuse, and 25% "other". African American patients had greater total body image dissatisfaction (p=0.002), specifically with respect to digital ulcers, pruritus, and pigmentation changes, than Caucasian participants. Patients with diffuse SSc had greater body image dissatisfaction than those with limited disease (p=0.002). CONCLUSIONS: Our results suggest that African American patients with SSc and those with diffuse subtype suffer a higher degree of body image dissatisfaction. Screening for and addressing this issue in SSc patients is prudent. Further study is needed to understand racial differences in body image dissatisfaction among patients with SSc. PMID- 27192126 TI - A Comparative Analysis of the Legal and Bioethical Frameworks Governing the Secondary Use of Data for Research Purposes. AB - The secondary use of research and health data for purposes that differ from the original purpose of the collection is becoming a major trend in research, since it allows for the optimal use of already available resources, and reduces the costs of research activities. However, the consent provided at the time of the initial data collection might not have foreseen these new uses of the data. This is especially true for biobanks having collected data under a restricted or a disease-specific consent, and for data linkage, which allows researchers to combine research data with information from the medical record of participants. To protect the participants' privacy, confidentiality, and autonomy, the use of identifiable research and clinical data for secondary research purposes is governed by a rather complex legal and ethical framework. This article aims to: (1) provide a comprehensive analysis of the legal and bioethical framework governing the secondary use of data at the international level, and; (2) identify points of convergence and divergence with regard to the secondary use of data for research purposes, in five countries (Australia, Canada, France, United Kingdom, and United States). While the secondary use of already collected data carries benefits and drawbacks, the international and national legal framework provide guidance to promote a wider (although limited) secondary use of data, while protecting research participants' rights and interests. Despite some differences, the similarities between international and national regulations and norms reveal the emergence of a common set of criteria for the secondary use of data in international research. PMID- 27192127 TI - Oncogenetics service and the Brazilian public health system: the experience of a reference Cancer Hospital. AB - The identification of families at-risk for hereditary cancer is extremely important due to the prevention potential in those families. However, the number of Brazilian genetic services providing oncogenetic care is extremely low for the continental dimension of the country and its population. Therefore, at-risk patients do not receive appropriate assistance. This report describes the creation, structure and management of a cancer genetics service in a reference center for cancer prevention and treatment, the Barretos Cancer Hospital (BCH). The Oncogenetics Department (OD) of BCH offers, free of charge, to all patients/relatives with clinical criteria, the possibility to perform i) genetic counseling, ii) preventive examinations and iii) genetic testing with the best quality standards. The OD has a multidisciplinary team and is integrated with all specialties. The genetic counseling process consists (mostly) of two visits. In 2014, 614 individuals (371 families) were seen by the OD. To date, over 800 families were referred by the OD for genetic testing. The support provided by the Oncogenetics team is crucial to identify at-risk individuals and to develop preventive and personalized behaviors for each situation, not only to the upper middle class population, but also to the people whose only possibility is the public health system. PMID- 27192128 TI - The lipidome, genotoxicity, hematotoxicity and antioxidant properties of andiroba oil from the Brazilian Amazon. AB - Andirobeira is an Amazonian tree, the seeds of which produce a commercially valuable oil that is used in folk medicine and in the cosmetic industry. Andiroba oil contains components with anti-inflammatory, cicatrizing and insect-repellant actions. However, virtually nothing is known of the safety of this oil for humans. The aim of this work was therefore to investigate the hematotoxicity, genotoxicity and mutagenicity of andiroba oil using the comet and micronucleus assays, and to assess its antioxidant properties and lipidome as a means of addressing safety issues. For the experiments, andiroba oil was administered by gavage for 14 consecutive days in nulliparous female Swiss mice randomly distributed in four groups: negative control and three doses of oil (500, 1000 and 2000 mg/kg/day). These doses were chosen based on recommendations of the OECD guideline no. 474 (1997). GC/MS was used to investigate the free fatty acid, cholesterol and triterpene content of andiroba oil in a lipidomic analysis. No clinical or behavioral alterations were observed throughout the period of treatment, and exposure to andiroba oil at the doses and conditions used here did not result in hematotoxic, genotoxic or mutagenic effects. Tests in vitro showed that oil sample 3 from southwestern of Brazilian Amazon had a high antioxidant capacity that may protect biological systems from oxidative stress, although this activity remains to be demonstrated in vivo. PMID- 27192129 TI - CDH1 mutations in gastric cancer patients from northern Brazil identified by Next Generation Sequencing (NGS). AB - Gastric cancer is considered to be the fifth highest incident tumor worldwide and the third leading cause of cancer deaths. Developing regions report a higher number of sporadic cases, but there are only a few local studies related to hereditary cases of gastric cancer in Brazil to confirm this fact. CDH1 germline mutations have been described both in familial and sporadic cases, but there is only one recent molecular description of individuals from Brazil. In this study we performed Next Generation Sequencing (NGS) to assess CDH1 germline mutations in individuals who match the clinical criteria for Hereditary Diffuse Gastric Cancer (HDGC), or who exhibit very early diagnosis of gastric cancer. Among five probands we detected CDH1 germline mutations in two cases (40%). The mutation c.1023T > G was found in a HDGC family and the mutation c.1849G > A, which is nearly exclusive to African populations, was found in an early-onset case of gastric adenocarcinoma. The mutations described highlight the existence of gastric cancer cases caused by CDH1 germline mutations in northern Brazil, although such information is frequently ignored due to the existence of a large number of environmental factors locally. Our report represent the first CDH1 mutations in HDGC described from Brazil by an NGS platform. PMID- 27192130 TI - Hereditary cancer risk assessment: insights and perspectives for the Next Generation Sequencing era. AB - Hereditary cancer risk assessment is a multidisciplinary and dynamic process, with the purpose of estimating probabilities of germline mutations in cancer susceptibility genes and assessing empiric risks of cancer based on personal and family histories, in order to offer clinical and molecular diagnoses and clinical management based on these risks. Genetic tests are available and most of them are reimbursed by insurance companies, although they are generally not covered by the public health systems of developing countries. More recently, molecular diagnosis of hereditary cancer is feasible through next-generation sequencing (NGS) panels. Here we review the benefits and limitations of NGS technologies in the clinical practice. PMID- 27192131 TI - Proteomic analysis of halotolerant proteins under high and low salt stress in Dunaliella salina using two-dimensional differential in-gel electrophoresis. AB - Dunaliella salina, a single-celled marine alga with extreme salt tolerance, is an important model organism for studying fundamental extremophile survival mechanisms and their potential practical applications. In this study, two dimensional differential in-gel electrophoresis (2D-DIGE) was used to investigate the expression of halotolerant proteins under high (3 M NaCl) and low (0.75 M NaCl) salt concentrations. Matrix-assisted laser desorption ionization time-of flight mass spectrometry (MALDI-TOF/TOF MS) and bioinformatics were used to identify and characterize the differences among proteins. 2D-DIGE analysis revealed 141 protein spots that were significantly differentially expressed between the two salinities. Twenty-four differentially expressed protein spots were successfully identified by MALDI-TOF/TOF MS, including proteins in the following important categories: molecular chaperones, proteins involved in photosynthesis, proteins involved in respiration and proteins involved in amino acid synthesis. Expression levels of these proteins changed in response to the stress conditions, which suggests that they may be involved in the maintenance of intracellular osmotic pressure, cellular stress responses, physiological changes in metabolism, continuation of photosynthetic activity and other aspects of salt stress. The findings of this study enhance our understanding of the function and mechanisms of various proteins in salt stress. PMID- 27192132 TI - Physiological and perceptual effects of precooling in wheelchair basketball athletes. AB - OBJECTIVE: To investigate the physiological and perceptual effects of three precooling strategies during pre-exercise rest in athletes with a spinal cord injury (SCI). DESIGN: Randomized, counterbalanced. Participants were precooled, then rested for 60 minutes (22.7 +/- 0.2 degrees C, 64.2 +/- 2.6%RH). SETTING: National Wheelchair Basketball Training Centre, Australia. PARTICIPANTS: Sixteen wheelchair basketball athletes with a SCI. INTERVENTIONS: Participants were precooled through; 1) 10 minutes of 15.8 degrees C cold water immersion (CWI), 2) ingestion of 6.8 g/kg-1 of slushie (S) from sports drink; 3) ingestion of 6.8 g/kg-1 of slushie with application of iced towels to the legs, torso and back/arms (ST); or 4) ingestion of 6.8 g/kg-1 of room temperature (22.3 degrees C) sports drink (CON). OUTCOME MEASURES: Core temperature (Tgi), skin temperature (Tsk), heart rate (HR), and thermal and gastrointestinal comfort. RESULTS: Following CWI, a significant reduction in Tgi was observed compared to CON, with a greatest reduction of 1.58 degrees C occurring 40 minutes post-cooling (95% CI [1.07, 2.10]). A significant reduction in Tgi following ST compared to CON was also observed at 20 minutes (0.56 degrees C; [0.03, 1.09]) and 30 minutes (0.56 degrees C; [0.04, 1.09]) post-cooling. Additionally, a significant interaction between impairment level and time was observed for Tgi and HR, demonstrating athletes with a higher level of impairment experienced a greater reduction in HR and significant decrease in rate of decline in Tgi, compared to lesser impaired athletes. CONCLUSION: CWI and ST can effectively lower body temperature in athletes with a SCI, and may assist in tolerating warm conditions. PMID- 27192135 TI - Doctor to Doctor. PMID- 27192136 TI - Winter emergencies. PMID- 27192137 TI - The spirit of Christmas in a doctor's bag. PMID- 27192134 TI - Local Structure in Terms of Nearest-Neighbor Approach in 1-Butyl-3 methylimidazolium-Based Ionic Liquids: MD Simulations. AB - Description of the local microscopic structure in ionic liquids (ILs) is a prerequisite to obtain a comprehensive understanding of the influence of the nature of ions on the properties of ILs. The local structure is mainly determined by the spatial arrangement of the nearest neighboring ions. Therefore, the main interaction patterns in ILs, such as cation-anion H-bond-like motifs, cation cation alkyl tail aggregation, and ring stacking, were considered within the framework of the nearest-neighbor approach with respect to each particular interaction site. We employed classical molecular dynamics (MD) simulations to study in detail the spatial, radial, and orientational relative distribution of ions in a set of imidazolium-based ILs, in which the 1-butyl-3-methylimidazolium (C4mim(+)) cation is coupled with the acetate (OAc(-)), chloride (Cl(-)), tetrafluoroborate (BF4(-)), hexafluorophosphate (PF6(-)), trifluoromethanesulfonate (TfO(-)), or bis(trifluoromethanesulfonyl)amide (TFSA( )) anion. It was established that several structural properties are strongly anion-specific, while some can be treated as universally applicable to ILs, regardless of the nature of the anion. Namely, strongly basic anions, such as OAc(-) and Cl(-), prefer to be located in the imidazolium ring plane next to the C-H(2/4-5) sites. By contrast, the other four bulky and weakly coordinating anions tend to occupy positions above/below the plane. Similarly, the H-bond-like interactions involving the H(2) site are found to be particularly enhanced in comparison with the ones at H(4-5) in the case of asymmetric and/or more basic anions (C4mimOAc, C4mimCl, C4mimTfO, and C4mimTFSA), in accordance with recent spectroscopic and theoretical findings. Other IL-specific details related to the multiple H-bond-like binding and cation stacking issues are also discussed in this paper. The secondary H-bonding of anions with the alkyl hydrogen atoms of cations as well as the cation-cation alkyl chain aggregation turned out to be poorly sensitive to the nature of the anion. PMID- 27192133 TI - Exploring Relationships Among Experience of Regret, Delay Discounting, and Worries About Future Effects of Smoking Among Current Smokers. AB - BACKGROUND: Smoking regret differs by smoker characteristics (dependence) and may be linked to delay discounting (DD), where smaller immediate rewards are preferred to larger delayed rewards. It is hypothesized that those who exhibit stronger tendencies to delay rewards also express fewer future health concerns and possibly less regret about smoking. OBJECTIVES: The objective is to determine the interrelationships of regret, dependence, and delay discounting among current smokers. METHODS: In July 2010, 1062 smokers completed a 45-minute at-home web based survey and answered questions including regret, dependence (Fagerstrom Test for Cigarette Dependence), and delay discounting (Monetary Choice Questionnaire). Relationships among these variables and perceived future health effects were analyzed using correlations, repeated measures analysis of variance, and generalized linear models. RESULTS: Most smokers (85%) regretted smoking. FTCD and log-k (DD) scores were positively associated (rs = 0.15, p < .001). Though a strong decline in log-k was shown as reward increased (p's < .001), there were no differences in discounting by regret. Regret was positively associated with worries concerning health effects, quality of life, and finances (p's < .001). Little association was found between DD and future health concerns. CONCLUSIONS/IMPORTANCE: Though this study confirms that regret for smoking is associated with perceived future risks as well as supports previous findings between FTCD and DD, it shows little association between DD and perceived future risks. PMID- 27192139 TI - Cme Credit QUIZ. PMID- 27192141 TI - Frostbite. PMID- 27192142 TI - South Philadelphia passive sampler and sensor study. AB - From June 2013 to March 2015, in total 41 passive sampler deployments of 2 wk duration each were conducted at 17 sites in South Philadelphia, PA, with results for benzene discussed here. Complementary time-resolved measurements with lower cost prototype fenceline sensors and an open-path ultraviolet differential optical absorption spectrometer were also conducted. Minimum passive sampler benzene concentrations for each sampling period ranged from 0.08 ppbv to 0.65 ppbv, with a mean of 0.25 ppbv, and were negatively correlated with ambient temperature (-0.01 ppbv/ degrees C, R(2) = 0.68). Co-deployed duplicate passive sampler pairs (N = 609) demonstrated good precision with an average and maximum percent difference of 1.5% and 34%, respectively. A group of passive samplers located within 50 m of a refinery fenceline had a study mean benzene concentration of 1.22 ppbv, whereas a group of samplers located in communities >1 km distant from facilities had a mean of 0.29 ppbv. The difference in the means of these groups was statistically significant at the 95% confidence level (p < 0.001). A decreasing gradient in benzene concentrations moving away from the facilities was observed, as was a significant period-to-period variation. The highest recorded 2-wk average benzene concentration for the fenceline group was 3.11 ppbv. During this period, time-resolved data from the prototype sensors and the open-path spectrometer detected a benzene signal from the west on one day in particular, with the highest 5-min path-averaged benzene concentration measured at 24 ppbv. IMPLICATIONS: Using a variation of EPA's passive sampler refinery fenceline monitoring method, coupled with time-resolved measurements, a multiyear study in South Philadelphia informed benzene concentrations near facilities and in communities. The combination of measurement strategies can assist facilities in identification and mitigation of emissions from fugitive sources and improve information on air quality complex air sheds. PMID- 27192143 TI - Embodying health identities: A study of young people with asthma. AB - The embodiment of health identities is a growing area of interest. Questions posed in this literature include: how important is the body in our understandings/experiences of health, how are everyday definitions of health and self embodied despite chronic illness, and how do social relations influence these interpretations? Mindful of such questions, this paper draws on a qualitative study of mild to moderate asthma among young people in Ireland. In depth interviews were undertaken with 31 respondents aged between 5 and 17, including boys (n = 15) and girls (n = 16) from different class and ethnic backgrounds. Core themes included: the importance of play, physical activity and sport; diet/nutrition; and physical appearance. Asthma sometimes presented challenges in relation to specific domains, notably strenuous physical activity, though in many other respects its potential impact was discursively minimised. Attentive to various modalities of the lived body, we illustrate how health identities are negotiated among young people diagnosed with a chronic illness. Connections are also made with the sociology of childhood and (ill) health, which views young people as active agents. PMID- 27192144 TI - Cell Permeating Nano-Complexes of Amphiphilic Polyelectrolytes Enhance Solubility, Stability, and Anti-Cancer Efficacy of Curcumin. AB - Many hydrophobic drugs encounter severe bioavailability issues owing to their low aqueous solubility and limited cellular uptake. We have designed a series of amphiphilic polyaspartamide polyelectrolytes (PEs) that solubilize such hydrophobic drugs in aqueous medium and enhance their cellular uptake. These PEs were synthesized through controlled (~20 mol %) derivatization of polysuccinimide (PSI) precursor polymer with hydrophobic amines (of varying alkyl chain lengths, viz. hexyl, octyl, dodecyl, and oleyl), while the remaining succinimide residues of PSI were opened using a protonable and hydrophilic amine, 2-(2-amino-ethyl amino) ethanol (AE). Curcumin (Cur) was employed as a representative hydrophobic drug to explore the drug-delivery potential of the resulting PEs. Unprecedented enhancement in the aqueous solubility of Cur was achieved by employing these PEs through a rather simple protocol. In the case of PEs containing oleyl/dodecyl residues, up to >65000* increment in the solubility of Cur in aqueous medium could be achieved without requiring any organic solvent at all. The resulting suspensions were physically and chemically stable for at least 2 weeks. Stable nanosized polyelectrolyte complexes (PECs) with average hydrodynamic diameters (DH) of 150-170 nm (without Cur) and 220-270 nm (after Cur loading) were obtained by using submolar sodium polyaspartate (SPA) counter polyelectrolyte. The zeta potential of these PECs ranged from +36 to +43 mV. The PEC-formation significantly improved the cytocompatibility of the PEs while affording reconstitutable nanoformulations having up to 40 wt % drug-loading. The Cur loaded PECs were readily internalized by mammalian cells (HEK-293T, MDA-MB-231, and U2OS), majorly through clathrin-mediated endocytosis (CME). Cellular uptake of Cur was directly correlated with the length of the alkyl chain present in the PECs. Further, the PECs significantly improved nuclear transport of Cur in cancer cells, resulting in their death by apoptosis. Noncancerous cells were completely unaffected under this treatment. PMID- 27192145 TI - A prebiotic role of Ecklonia cava improves the mortality of Edwardsiella tarda infected zebrafish models via regulating the growth of lactic acid bacteria and pathogen bacteria. AB - In this study, the beneficial prebiotic roles of Ecklonia cava (E. cava, EC) were evaluated on the growth of lactic acid bacteria (LAB) and pathogen bacteria and the mortality of pathogen-bacteria infected zebrafish model. The result showed that the original E. cava (EC) led to the highest growth effects on three LABs (Lactobacillus brevis, L. brevis; Lactobacillus pentosus, L. pentosus; Lactobacillus plantarum; L. plantarum) and it was dose-dependent manners. Also, EC, its Celluclast enzymatic (ECC) and 100% ethanol extracts (ECE) showed the anti-bacterial activities on the fish pathogenic bacteria such as (Edwardsiella tarda; E. tarda, Streptococcus iniae; S. iniae, and Vibrio harveyi; V. harveyi). Interestingly, EC induced the higher production of the secondary metabolites from L. plantarum in MRS medium. The secondary metabolites produced by EC significantly inhibited the growth of pathogen bacteria. In further in vivo study, the co-treatment of EC and L. plantarum improved the growth and mortality of E. tarda-infected zebrafish as regulating the expression of inflammatory molecules such as iNOS and COX2. Taken together, our present study suggests that the EC plays an important role as a potential prebiotic and has a protective effect against the infection caused by E. tarda injection in zebrafish. Also, our conclusion from this evidence is that EC can be used and applied as a useful prebiotic. PMID- 27192146 TI - Differentially proteomic analysis of the Chinese shrimp at WSSV latent and acute infection stages by iTRAQ approach. AB - As the direct executors of biological function, the expression level of proteins will reveal the molecular mechanisms regulating WSSV acute infection more directly. In the present study, the iTRAQ approach was applied to identifying differentially expressed proteins in Chinese shrimp during WSSV latent infection and acute infection. A total of 4051 unique peptides corresponding to 1286 proteins were identified. 118 unique proteins showed differential up-regulation and 122 proteins were down-regulated in shrimp during WSSV acute infection compared with those in WSSV latent infection stage. A number of proteins related to actin-myosin cytoskeleton process, including myosin, actin, tubulin, clathrin, and tropomyosin were found up-regulated in shrimp at WSSV AI stage, indicating that the phagocytosis process was involved in WSSV AI stage. The apoptosis process in shrimp during WSSV AI seemed to be inhibited because some proteins suppressive on apoptosis were up-regulated, such as ALG-2 interacting protein x, Hsp90, 14-3-3-like protein, peroxiredoxin 5, peroxiredoxin 6 and adenine nucleotide translocase 2. Association analysis between the proteomic data and the previous transcriptome data was performed. Quantitative real-time PCR and western blot were carried out to verify the reliability of the proteomics data. The present study provided a comprehensive view of molecular mechanisms regulating WSSV acute infection at the protein level. PMID- 27192148 TI - A New Centrosaurine Ceratopsid, Machairoceratops cronusi gen et sp. nov., from the Upper Sand Member of the Wahweap Formation (Middle Campanian), Southern Utah. AB - The Upper Cretaceous (middle-late Campanian) Wahweap Formation of southern Utah contains the oldest diagnostic evidence of ceratopsids (to date, all centrosaurines) in North America, with a number of specimens recovered from throughout a unit that spans between 81 and 77 Ma. Only a single specimen has been formally named, Diabloceratops eatoni, from the lower middle member of the formation. Machairoceratops cronusi gen. et sp. nov., a new centrosaurine ceratopsid from the upper member of the Wahweap Formation, is here described based on cranial material representing a single individual recovered from a calcareous mudstone. The specimen consists of two curved and elongate orbital horncores, a left jugal, a nearly complete, slightly deformed braincase, the left squamosal, and a mostly complete parietal ornamented by posteriorly projected, anterodorsally curved, elongate spikes on either side of a midline embayment. The fan-shaped, stepped-squamosal is diagnostic of Centrosaurinae, however, this element differs from the rectangular squamosal in Diabloceratops. Machairoceratops also differs in the possession of two anterodorsally (rather than laterally) curved epiparietal ornamentations on either side of a midline embayment that are distinguished by a posteromedially-oriented sulcus along the entire length of the epiparietal. Additionally, the parietosquamosal frill is lacking any other epiossifications along its periphery. Machairoceratops shares a triangular (rather than round) frill and spike-like epiparietal loci (p1) ornamentation with the stratigraphically lower Diabloceratops. Both parsimony and Bayesian phylogenetic analyses place Machairoceratops as an early-branching centrosaurine. However, the parsimony-based analysis provides little resolution for the position of the new taxon, placing it in an unresolved polytomy with Diabloceratops. The resultant Bayesian topology yielded better resolution, aligning Machairoceratops as the definitive sister taxon to a clade formed by Diabloceratops and Albertaceratops. Considered together, both phylogenetic methods unequivocally place Machairoceratops as an early-branching centrosaurine, and given the biostratigraphic position of Machairoceratops, these details increase the known ceratopsid diversity from both the Wahweap Formation and the southern portion of Laramidia. Finally, the unique morphology of the parietal ornamentation highlights the evolutionary disparity of frill ornamentation near the base of Centrosaurinae. PMID- 27192147 TI - Host Immune Responses Differ between M. africanum- and M. tuberculosis-Infected Patients following Standard Anti-tuberculosis Treatment. AB - Epidemiological differences exist between Mycobacterium africanum (Maf)- and Mycobacterium tuberculosis (Mtb)-infected patients, but to date, contributing host factors have not been characterised. We analysed clinical outcomes, as well as soluble markers and gene expression profiles in unstimulated, and ESAT6/CFP-10 , whole-Maf- and Mtb-stimulated blood samples of 26 Maf- and 49 Mtb-HIV-negative tuberculosis patients before, and after 2 and 6 months of anti-tuberculosis therapy. Before treatment, both groups had similar clinical parameters, but differed in few cytokines concentration and gene expression profiles. Following treatment the body mass index, skinfold thickness and chest X-ray scores showed greater improvement in the Mtb- compared to Maf-infected patients, after adjusting for age, sex and ethnicity (p = 0.02; 0.04 and 0.007, respectively). In addition, in unstimulated blood, IL-12p70, IL12A and TLR9 were significantly higher in Maf-infected patients, while IL-15, IL-8 and MIP-1alpha were higher in Mtb-infected patients. Overnight stimulation with ESAT-6/CFP-10 induced significantly higher levels of IFN-gamma and TNF-alpha production, as well as gene expression of CCL4, IL1B and TLR4 in Mtb- compared to Maf-infected patients. Our study confirms differences in clinical features and immune genes expression and concentration of proteins associated with inflammatory processes between Mtb- and Maf-infected patients following anti-tuberculosis treatment These findings have public health implications for treatment regimens, and biomarkers for tuberculosis diagnosis and susceptibility. PMID- 27192149 TI - The Relationships between Workaholism and Symptoms of Psychiatric Disorders: A Large-Scale Cross-Sectional Study. AB - Despite the many number of studies examining workaholism, large-scale studies have been lacking. The present study utilized an open web-based cross-sectional survey assessing symptoms of psychiatric disorders and workaholism among 16,426 workers (Mage = 37.3 years, SD = 11.4, range = 16-75 years). Participants were administered the Adult ADHD Self-Report Scale, the Obsession-Compulsive Inventory Revised, the Hospital Anxiety and Depression Scale, and the Bergen Work Addiction Scale, along with additional questions examining demographic and work-related variables. Correlations between workaholism and all psychiatric disorder symptoms were positive and significant. Workaholism comprised the dependent variable in a three-step linear multiple hierarchical regression analysis. Basic demographics (age, gender, relationship status, and education) explained 1.2% of the variance in workaholism, whereas work demographics (work status, position, sector, and annual income) explained an additional 5.4% of the variance. Age (inversely) and managerial positions (positively) were of most importance. The psychiatric symptoms (ADHD, OCD, anxiety, and depression) explained 17.0% of the variance. ADHD and anxiety contributed considerably. The prevalence rate of workaholism status was 7.8% of the present sample. In an adjusted logistic regression analysis, all psychiatric symptoms were positively associated with being a workaholic. The independent variables explained between 6.1% and 14.4% in total of the variance in workaholism cases. Although most effect sizes were relatively small, the study's findings expand our understanding of possible psychiatric predictors of workaholism, and particularly shed new insight into the reality of adult ADHD in work life. The study's implications, strengths, and shortcomings are also discussed. PMID- 27192150 TI - Coping styles used by sexual minority men who experience intimate partner violence. AB - AIMS AND OBJECTIVES: This study examined the coping styles used by sexual minority men who have experienced intimate partner violence, including sexual, emotional and physical victimisation, as well as physical injury. BACKGROUND: Although sexual minority men experience intimate partner violence at least as often as do heterosexuals, there is currently limited knowledge of intimate partner violence in this community or resources for sexual minority men who experience intimate partner violence. DESIGN: Cross-sectional design. METHOD: Sexual minority men (N = 89) were recruited as part of a national online survey and completed questionnaires assessing lifetime experiences of intimate partner violence as well as various coping strategies. In terms of intimate partner violence, 34.8% of participants reported having been targets of sexual abuse, 38.2% targets of physical abuse, 69.7% targets of psychological abuse and 28.1% had experienced an injury as a result of intimate partner violence during their lifetime. RESULTS: Canonical correlation analyses found that intimate partner violence victimisation explained 32.5% of the variance in adaptive and 31.4% of the variance in maladaptive coping behaviours. In the adaptive coping canonical correlation, standardised loadings suggested that sexual minority men who experienced intimate partner violence resulting in injury were more likely to use religious coping, but less likely to use planning coping. In the maladaptive coping canonical correlation, sexual minority men who had been targets of intimate partner sexual victimisation and intimate partner violence resulting in injury tended to engage in increased behavioural disengagement coping. CONCLUSION: This study revealed several coping behaviours that are more or less likely as the severity of different forms of intimate partner violence increases. RELEVANCE TO CLINICAL PRACTICE: The identification of these coping styles could be applied to the development and modification of evidence-based interventions to foster effective and discourage ineffective coping styles, thereby improving outcomes for sexual minority men who experience intimate partner violence. PMID- 27192152 TI - Correction: Investigating the Role of RIO Protein Kinases in Caenorhabditis elegans. AB - [This corrects the article DOI: 10.1371/journal.pone.0117444.]. PMID- 27192154 TI - Consultations by Asylum Seekers: Recent Trends in the Emergency Department of a Swiss University Hospital. AB - BACKGROUND: Large-scale war-related migration to Switzerland and other European countries is currently challenging European health systems. Little is known about recent patterns and trends in Emergency Department (ED) consultations by Asylum Seekers (AS). METHODS: A retrospective single-centre analysis was performed of the data from all adult patients with the official status of "Asylum Seeker" or "Refugee" who consulted the ED of Bern University Hospital, Switzerland, between June 2012 and June 2015. Patient characteristics and clinical information, such as triage category, type of referral and discharge, violence-related injury and diagnostic group on discharge, were extracted from the computerised database or determined from the medical reports. Changes in categorical variables between the three studied years were described. RESULTS: A total of 1,653 eligible adult patients were identified in the 3-year period. Between the first (06/12-06/13) and third periods (06/14-06/15), the number of presentations per year increased by about 45%. The AS came from 62 different nations, the most common countries being Eritrea (13%), Somalia (13%) and Syria (11%). The mean age was 33.3 years (SD 12.3) and two thirds (65.7%) were male. The proportion of women increased over time. Moreover the relative proportions shifted from patients between 20 and 50 years to patients of under 20 or over 60 years. Nearly two thirds of the patients were walk-in emergencies and this proportion increased over time. The mean triage score was 2.9 (SD 0.7), with more than 90% presenting as "urgent consultation". About half of the patients were treated for trauma (17.2%), infections (16.8%) or psychiatric problems (14.2%). Trauma was seen in a higher proportion of male than female patients. About 25% of the patients were admitted for in-hospital treatment. CONCLUSIONS: The recent rise in AS in the population has lead to an increase in AS presenting to EDs. This changes the composition of ED patients and should raise awareness that changes in procedures may be needed. Infectious diseases and psychiatric problems remain a heavy burden for AS presenting in the ED. A trend towards an increasing proportion of walk-in patients to the ED could not be explained by this study. Further studies and surveillance are needed to investigate this trend. PMID- 27192155 TI - Case Report: Coexistence of SUNCT and Hypnic Headache in the Same Patient. AB - BACKGROUND: Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and hypnic headache (HH) are two exceedingly rare and distinctly classified primary headaches. The hypothalamus seems to be a crucial region involved in the pathophysiology of both conditions, but no cases of SUNCT and HH co-occurrence have been described so far. CASE RESULTS: A 49-year-old woman who has been suffering from SUNCT for years, with alternation of symptomatic periods and remissions, developed a new headache with different clinical features, presenting exclusively during sleep and with a dramatic responsiveness to caffeine, that met the diagnostic criteria for HH. CONCLUSIONS: The available literature suggests that SUNCT and HH are different conditions but the association in the same patient that we describe supports the concept that they are not mutually exclusive. Further studies are needed to establish if they share a common pathophysiological mechanism. PMID- 27192151 TI - Boosting with Subtype C CN54rgp140 Protein Adjuvanted with Glucopyranosyl Lipid Adjuvant after Priming with HIV-DNA and HIV-MVA Is Safe and Enhances Immune Responses: A Phase I Trial. AB - BACKGROUND: A vaccine against HIV is widely considered the most effective and sustainable way of reducing new infections. We evaluated the safety and impact of boosting with subtype C CN54rgp140 envelope protein adjuvanted in glucopyranosyl lipid adjuvant (GLA-AF) in Tanzanian volunteers previously given three immunizations with HIV-DNA followed by two immunizations with recombinant modified vaccinia virus Ankara (HIV-MVA). METHODS: Forty volunteers (35 vaccinees and five placebo recipients) were given two CN54rgp140/GLA-AF immunizations 30-71 weeks after the last HIV-MVA vaccination. These immunizations were delivered intramuscularly four weeks apart. RESULTS: The vaccine was safe and well tolerated except for one episode of asymptomatic hypoglycaemia that was classified as severe adverse event. Two weeks after the second HIV-MVA vaccination 34 (97%) of the 35 previously vaccinated developed Env-specific binding antibodies, and 79% and 84% displayed IFN-gamma ELISpot responses to Gag and Env, respectively. Binding antibodies to subtype C Env (included in HIV-DNA and protein boost), subtype B Env (included only in HIV-DNA) and CRF01_AE Env (included only in HIV-MVA) were significantly boosted by the CN54rgp140/GLA-AF immunizations. Functional antibodies detected using an infectious molecular clone virus/peripheral blood mononuclear cell neutralization assay, a pseudovirus/TZM bl neutralization assay or by assays for antibody-dependent cellular cytotoxicity (ADCC) were not significantly boosted. In contrast, T-cell proliferative responses to subtype B MN antigen and IFN-gamma ELISpot responses to Env peptides were significantly enhanced. Four volunteers not primed with HIV-DNA and HIV-MVA before the CN54rgp140/GLA-AF immunizations mounted an antibody response, while cell-mediated responses were rare. After the two Env subtype C protein immunizations, a trend towards higher median subtype C Env binding antibody titers was found in vaccinees who had received HIV-DNA and HIV-MVA prior to the two Env protein immunizations as compared to unprimed vaccinees (p = 0.07). CONCLUSION: We report excellent tolerability, enhanced binding antibody responses and Env-specific cell-mediated immune responses but no ADCC antibody increase after two immunizations with a subtype C rgp140 protein adjuvanted in GLA-AF in healthy volunteers previously immunized with HIV-DNA and HIV-MVA. TRIAL REGISTRATION: International Clinical Trials Registry PACTR2010050002122368. PMID- 27192153 TI - Efficient method for volumetric assessment of peak blood flow velocity using 4D flow MRI. AB - PURPOSE: To test the feasibility and effectiveness of using maximum intensity plots (MIPs) based on 4D flow magnetic resonance imaging (MRI) velocity data to assess systolic peak velocities in a cohort of bicuspid aortic valve (BAV) patients. MATERIALS AND METHODS: 4D flow MRI at 1.5T was performed on 51 BAV patients. MIPs were generated from the 4D flow MRI velocity data and used by two users to determine peak velocities in three regions of interest (ROIs): ascending aorta (AAo), aortic arch, and descending aorta. 4D flow MRI peak velocities in the AAo were compared to peak velocities recorded by 2D phase contrast MRI (2D PCMRI) in a subcohort of 36 patients and by Doppler echocardiography in a subcohort of 34 patients. 4D flow MRI peak velocities recorded by each observer were compared for all ROIs to test for interobserver variability. RESULTS: 4D flow MRI recorded significantly higher velocities compared to 2D PCMRI (2.04 +/- 0.71 m/s vs. 1.69 +/- 0.79 m/s, 17.2% difference, P < 0.001) and similar velocities compared to Doppler echocardiography. There was excellent agreement between the observers, with a mean difference of 0.005 m/s and an intraclass correlation coefficient of 0.98. CONCLUSION: 4D flow MRI velocity MIPs allow for efficient measurement of peak velocities in BAV patients with higher accuracy than 2D PCMRI and similar accuracy to Doppler echocardiography. J. Magn. Reson. Imaging 2016;44:1673-1682. PMID- 27192156 TI - Prognostic impact of perineural invasion in hypopharyngeal squamous cell carcinoma. AB - OBJECTIVES: The aim of this study was to evaluate the role of PNI in HPSCC. METHODS: The medical records of 105 patients who underwent surgery-based treatment for HPSCC were reviewed. Clinicopathologic parameters including disease specific survival were correlated with PNI. RESULTS: PNI was identified in 27 of the 105 (25.7%) cases of HPSCC. Correlation analysis demonstrated that PNI in HPSCC was significantly correlated with pN classification (10.3% in N0/N1 vs 34.8% in N2/N3, p = 0.006). Patients with PNI had decreased 5-year disease specific survival with borderline significance (p = 0.065). In a sub-set of 31 patients who did not receive post-operative radiotherapy, PNI was determined to be a significant prognostic predictor (p = 0.033). In multivariate analysis, extracapsular invasion was the only independent prognostic factor for disease specific survival (p = 0.001). CONCLUSION: Perineural invasion (PNI) should be considered an independent predictor for cervical lymph node involvement. PNI status in primary hypopharyngeal squamous cell carcinoma (HPSCC) specimens should be considered in decisions concerning adjuvant radiotherapy. PMID- 27192159 TI - Predictive Factors of Spontaneous Reporting of Adverse Drug Reactions among Community Pharmacists. AB - PURPOSE: To evaluate the association between spontaneous reporting (SR) and the knowledge, attitude, and needs of community pharmacists (CPs), using a questionnaire following a conceptual model known as the mixed model of knowledge attitude-practices and the satisfaction of needs. METHODS: Self-administered questionnaires were used with a nationwide convenience sample of CPs between September 1, 2014 and November 25, 2014 in Korea. The association between SR and the predictive factors was evaluated using multivariate logistic regression analysis. RESULTS: In total, 1,001 questionnaires were analyzed. The mean age of the respondents and the number of years spent in community pharmacy practice were 45.6 years and 15.3 years, respectively. CPs with experience of SR was 29.4%. Being older than 60 (ORadj, 0.16; 95% CI, 0.06-0.42), having prior experience with adverse drug reactions (ADR) (ORadj, 6.46; 95% CI, 2.46-16.98), having higher specific knowledge of SR (ORadj, 3.58; 95% CI, 1.96-6.56), and having less concern about the obstacles to SR (ORadj, 0.36; 95% CI, 0.23-0.57) were significant contributing factors to SR. The main obstacles to SR included perception of ADRs as 'not serious ADR' (77.9%), 'already well known ADR' (81.5%), and 'uncertain about causality' (73.3%). CPs without reporting experience had greater concerns related to the reporting method and the liability of the pharmacy than those with reporting experience (p<0.05). CONCLUSIONS: Findings from our study showed around one in three CPs had ADR reporting experience in Korea, while 87.1% had prior experience with ADR cases. The knowledge of SR, prior experience of ADR, and less concern about the obstacles to SR were contributing factors for reporting levels. PMID- 27192160 TI - Serum C-reactive protein in food protein-induced enterocolitis syndrome versus food protein-induced proctocolitis in Japan. AB - BACKGROUND: Some infants with food protein-induced enterocolitis syndrome (FPIES) have increased serum C-reactive protein (CRP) and fever in Japan. The aim of this study was therefore to clarify and compare the incidence of this in patients with FPIES versus patients with food protein-induced proctocolitis (FPIP). METHODS: One hundred and sixteen infants with non-IgE-mediated gastrointestinal food allergies were enrolled in this study and classified into three phenotypes: FPIES presenting with vomiting and/or diarrhea (n = 47); FPIP with bloody stool alone (n =19); and the mixed phenotype (MP), bloody stool with vomiting and/or diarrhea (n = 50). RESULTS: Serum CRP was increased in 55.3% of the FPIES group, similar to that in the MP group (54.0%), and significantly higher than in the FPIP group (15.8%; P < 0.01). Fever was observed in 29.8% of the FPIES group, significantly higher than in the MP group (8.0%; P < 0.01) and in the FPIP group (0%; P < 0.05). Patients with fever had significantly higher serum CRP than patients without fever (median, 12.8 vs <0.2 mg/dL, P < 0.00001). CONCLUSIONS: Serum CRP was significantly higher in the FPIES group than in the FPIP group. This suggests that serum CRP is a useful marker for differentiating the pathogenesis of FPIES from FPIP. From the perspective of serum CRP, the pathology of the intestinal inflammation in MP subjects is suggested to be similar to that of FPIES. PMID- 27192161 TI - Organolead Halide Perovskites for Low Operating Voltage Multilevel Resistive Switching. AB - Organolead halide perovskites are used for low-operating-voltage multilevel resistive switching. Ag/CH3 NH3 PbI3 /Pt cells exhibit electroforming-free resistive switching at an electric field of 3.25 * 10(3) V cm(-1) for four distinguishable ON-state resistance levels. The migration of iodine interstitials and vacancies with low activation energies is responsible for the low-electric field resistive switching via filament formation and annihilation. PMID- 27192162 TI - A systematic review of the effectiveness of smartphone applications that encourage dietary self-regulatory strategies for weight loss in overweight and obese adults. AB - The aim of this paper is to systematically review the evidence to explore whether smartphone applications that use self-regulatory strategies are beneficial for weight loss in overweight and obese adults over the age of 18 years. Sixteen electronic databases were searched for articles published up to April 2015 including MEDLINE, OVID, Ingenta, PSYCARTICLES and PSYCINFO, CINAHL, Sportdiscus, Science Direct, Web of Knowledge, Cochrane Library, JSTOR, EBSCO, Proquest, Wiley and Google Scholar. Twenty nine eligible studies were retrieved of which six studies met the inclusion criteria. Studies that recruited participants under the age of 18 years, adults with a chronic condition or did not report weight loss outcomes were excluded. Study findings were combined using a narrative synthesis. Overall, evidence suggests that smartphone applications may be a useful tool for self-regulating diet for weight loss as participants in the smartphone application group in all studies lost at least some bodyweight. However, when compared to other self-monitoring methods, there was no significant difference in the amount of weight lost. Findings should be interpreted with caution based on the design of the studies and the comparator groups used. Future research needs to be more methodologically rigorous and incorporate measures of whether eating habits become healthier in addition to measuring weight and BMI. PMID- 27192165 TI - The Sialylation Pathway and Coronary Artery Disease. PMID- 27192166 TI - College and the grieving student: A mixed-methods analysis. AB - The current mixed-methods study examines how college students negotiate the grief process with the competing demands of college. Data were collected from 950 students at a regional comprehensive university and a research intensive institution. Quantitative findings revealed closeness to the deceased as a key positive predictor of mental health and academic difficulties and positive associations between changes in peer relationships and mental health difficulties. Qualitative findings showed that closeness to the deceased was associated with a greater sense of purpose in the college experience and findings suggested that institutions and their faculty encourage and exhibit more sensitivity about grief issues. PMID- 27192163 TI - Infectious Disease Risk Associated with Contaminated Propofol Anesthesia, 1989 2014(1). AB - Administration of propofol, the most frequently used intravenous anesthetic worldwide, has been associated with several iatrogenic infections despite its relative safety. Little is known regarding the global epidemiology of propofol related outbreaks and the effectiveness of existing preventive strategies. In this overview of the evidence of propofol as a source of infection and appraisal of preventive strategies, we identified 58 studies through a literature search in PubMed, Embase, and Lilacs for propofol-related infections during 1989-2014. Twenty propofol-related outbreaks have been reported, affecting 144 patients and resulting in 10 deaths. Related factors included reuse of syringes for multiple patients and prolonged exposure to the environment when vials were left open. The addition of antimicrobial drugs to the emulsion has been instituted in some countries, but outbreaks have still occurred. There remains a lack of comprehensive information on the effectiveness of measures to prevent future outbreaks. PMID- 27192164 TI - Characterization of ESBL- and AmpC-Producing and Fluoroquinolone-Resistant Enterobacteriaceae Isolated from Mouflons (Ovis orientalis musimon) in Austria and Germany. AB - The aim of this study was to investigate the presence of beta-lactamase producing or fluoroquinolone-resistant members of the family Enterobacteriaceae in European mouflons (Ovis orientalis musimon). The mouflon samples originated from nasal and perineal swabs and/or organ samples in cases of a suspected infection. Only one of the 32 mouflons was tested positive for the presence of Enterobacteriaceae that displayed either an ESBL/AmpC phenotype or were resistant to ciprofloxacin. The positively tested swab originated from a sample of the jejunal mucosa of a four-year old female mouflon. Two different colony morphotypes were identified as Escherichia coli and Klebsiella pneumoniae. These isolates were phenotypically and genotypically characterized in detail by a polyphasic approach. Both isolates were multi-drug resistant. The E. coli isolate belonged to the phylogenetic group B1 and sequence type (ST) 744 and harboured the beta-lactamase genes blaCTX-M-15 and blaOXA-1. The K. pneumoniae, identified as ST11, harboured the beta-lactamase genes blaSHV-11, blaOXA-1, and blaDHA-1 as well as the plasmid-mediated quinolone resistance (PMQR) gene qnrB55. The present study demonstrates that wild animals can acquire human-derived resistance determinants and such findings may indicate environmental pollution with resistance determinants from other sources. PMID- 27192168 TI - Conjunctival malignant melanoma in Denmark: epidemiology, treatment and prognosis with special emphasis on tumorigenesis and genetic profile. AB - Conjunctival malignant melanoma is a rare disease associated with considerable mortality. Most published data have been based on case reports or series of referred patients. In addition, very little is known about the genetic and epigenetic profile of conjunctival melanoma and the resemblance to uveal, cutaneous and mucosal melanoma. The aim was to determine the incidence rate of conjunctival melanoma, and to relate clinicopathological features and treatment to prognosis. A further aim was to determine the prevalence of BRAF mutations in conjunctival melanoma, to determine whether BRAF mutations are early events in pathogenesis, and relate clinicopathological features and prognosis to BRAF mutation status. Finally, we wanted to identify tumour-specific and prognostic microRNAs in conjunctival melanoma, and to compare these with the microRNA expression of other melanoma subtypes. In order to investigate these rare tumours, we studied all the conjunctival melanomas that had been surgically removed in Denmark over a period of 52 years (1960-2012). Tissue samples, clinical files, pathology reports and follow-up data were collected and re evaluated. Using droplet digital polymerase chain reaction and immunohistochemistry, we investigated BRAF mutations; and using microRNA expression profiling, we investigated differentially expressed microRNAs. The overall incidence of conjunctival melanoma was 0.5/1 000 000/year, and it increased in Denmark over 52 years. The increase was mainly caused by an increase in older patients (>65 years) and bulbar lesions. Clinicopathological features significantly associated with a poor prognosis were extrabulbar location, involvement of adjacent tissue structures, tumour thickness exceeding 2 mm and local tumour recurrence. Patients undergoing incisional biopsy and/or treatment involving excision without adjuvant therapy fared worse than patients treated with excision and any type of adjuvant treatment. We found that 35% (39/110) of conjunctival melanomas were BRAF-mutated, and the incidence of BRAF mutations was constant over time. BRAF-mutation status corresponded in conjunctival melanoma and paired premalignant lesions. BRAF mutations were more frequent in males, in young patients, and in tumours with a sun-exposed tumour location (bulbar conjunctiva or caruncle), with a mixed or non-pigmented colour, with absence of primary acquired melanosis, and with origin in a nevus. Immunohistochemistry was able to accurately detect BRAF V600E mutations. In univariate analysis, distant metastatic disease was associated with BRAF mutations. No prognostic associations with BRAF mutations were identified in multivariate analyses. MicroRNA expression analysis revealed 25 tumour-specific microRNAs in conjunctival melanoma. Five possibly oncogenic miRNAs (miR-20b-5p, miR-146b-5p, miR-146a-5p, miR-506-3p and miR-509-3p) were up-regulated. Seven microRNAs (miR-30d-5p, miR-138-5p, miR-146a 5p, miR-500a-5p, miR-501-3p, miR-501-5p and miR-502-3p) were significantly and simultaneously up-regulated in both stage T1 and stage T2 tumours, and were associated with increased tumour thickness. The expression of the 25 tumour specific microRNAs did not differ significantly between conjunctival melanoma and oral or nasal mucosal melanoma. In conclusion, the incidence of conjunctival melanoma increased in the Danish population from 1960 to 2012. From our findings of a distinct pattern of BRAF mutations and differentially expressed microRNAs, it is evident that conjunctival melanoma is closely related to cutaneous and other mucosal melanomas and bears less resemblance to uveal melanomas. This means that conjunctival melanoma patients may benefit from therapies that are effective for cutaneous and mucosal melanoma. Additionally, the identification of several up-regulated microRNAs may prove to be useful as prognostic or therapeutic targets in conjunctival melanoma. PMID- 27192167 TI - Longitudinal Changes in the Motor Learning-Related Brain Activation Response in Presymptomatic Huntington's Disease. AB - Neurocognitive decline, including deficits in motor learning, occurs in the presymptomatic phase of Huntington's disease (HD) and precedes the onset of motor symptoms. Findings from recent neuroimaging studies have linked these deficits to alterations in fronto-striatal and fronto-parietal brain networks. However, little is known about the temporal dynamics of these networks when subjects approach phenoconversion. Here, 10 subjects with presymptomatic HD were scanned with 15O-labeled water at baseline and again 1.5 years later while performing a motor sequence learning task and a kinematically matched control task. Spatial covariance analysis was utilized to characterize patterns of change in learning related neural activation occurring over time in these individuals. Pattern expression was compared to corresponding values in 10 age-matched healthy control subjects. Spatial covariance analysis revealed significant longitudinal changes in the expression of a specific learning-related activation pattern characterized by increasing activity in the right orbitofrontal cortex, with concurrent reductions in the right medial prefrontal and posterior cingulate regions, the left insula, left precuneus, and left cerebellum. Changes in the expression of this pattern over time correlated with baseline measurements of disease burden and learning performance. The network changes were accompanied by modest improvement in learning performance that took place concurrently in the gene carriers. The presence of increased network activity in the setting of stable task performance is consistent with a discrete compensatory mechanism. The findings suggest that this effect is most pronounced in the late presymptomatic phase of HD, as subjects approach clinical onset. PMID- 27192169 TI - The role of air pollution in COPD and implications for therapy. AB - INTRODUCTION: Exposure to many environmental conditions, apart from tobacco, as a risk factor for developing chronic obstructive pulmonary disease (COPD) has been comprehensively studied. AREAS COVERED: Global estimates of air pollution depict a scenario of a considerable burden on respiratory health. Exposure to biomass smoke and occupational inhaled agents have been described as potentially related to causing or aggravating COPD. A number of emerging natural or accidental disasters have been suggested as a new source of exposure. Management of COPD patients exposed to different substances should include avoidance, especially in the more susceptible populations and proper pharmacological treatment considering potential association with particular clinical presentations. Expert commentary: Altogether, the available information indicates that appraisal of different environmental pollution exposures is clinically relevant, and should be systematically evaluated in COPD. PMID- 27192171 TI - Do Childhood Adversities Predict Suicidality? Findings from the General Population of the Metropolitan Area of Sao Paulo, Brazil. AB - BACKGROUND: Childhood adversities have been associated with a number of medical and psychiatric outcomes. However, the reported effects that specific childhood adversities have on suicidality vary across studies. METHOD: This was a cross sectional, stratified, multistage area probability investigation of a general population in Brazil, designated the Sao Paulo Megacity Mental Health Survey. The World Mental Health Composite International Diagnostic Interview was applied in 5037 individuals >= 18 years of age, in order to assess 12 different adversities occurring during childhood and/or adolescence, as well as to look for associations between those adversities and subsequent suicidality in different age strata. RESULTS: Over half of the respondents reported at least one childhood adversity. Only physical abuse was consistently associated with suicide attempts in all subsequent life stages (OR = 2.1). Among adults 20-29 years of age, the likelihood of a suicide attempt was correlated with parental divorce, whereas suicidal ideation was associated with prior sexual abuse. Among adults over 30 years of age, physical illness and economic adversity emerged as relevant childhood adversities associated with suicide attempts, whereas sexual abuse, family violence, and economic adversity were associated with suicidal ideation. CONCLUSION: Childhood adversities, especially physical abuse, are likely associated with unfavorable consequences in subsequent years. For suicidality across a lifespan, the role of different childhood adversities must be examined independently. PMID- 27192172 TI - Targeting In-Stent-Stenosis with RGD- and CXCL1-Coated Mini-Stents in Mice. AB - Atherosclerotic lesions that critically narrow the artery can necessitate an angioplasty and stent implantation. Long-term therapeutic effects, however, are limited by excessive arterial remodeling. We here employed a miniaturized nitinol stent coated with star-shaped polyethylenglycole (star-PEG), and evaluated its bio-functionalization with RGD and CXCL1 for improving in-stent stenosis after implantation into carotid arteries of mice. Nitinol foils or stents (bare metal) were coated with star-PEG, and bio-functionalized with RGD, or RGD/CXCL1. Cell adhesion to star-PEG-coated nitinol foils was unaltered or reduced, whereas bio functionalization with RGD but foremost RGD/CXCL1 increased adhesion of early angiogenic outgrowth cells (EOCs) and endothelial cells but not smooth muscle cells when compared with bare metal foils. Stimulation of cells with RGD/CXCL1 furthermore increased the proliferation of EOCs. In vivo, bio-functionalization with RGD/CXCL1 significantly reduced neointima formation and thrombus formation, and increased re-endothelialization in apoE-/- carotid arteries compared with bare-metal nitinol stents, star-PEG-coated stents, and stents bio-functionalized with RGD only. Bio-functionalization of star-PEG-coated nitinol-stents with RGD/CXCL1 reduced in-stent neointima formation. By supporting the adhesion and proliferation of endothelial progenitor cells, RGD/CXCL1 coating of stents may help to accelerate endothelial repair after stent implantation, and thus may harbor the potential to limit the complication of in-stent restenosis in clinical approaches. PMID- 27192170 TI - Low Mutation Burden in Ovarian Cancer May Limit the Utility of Neoantigen Targeted Vaccines. AB - Due to advances in sequencing technology, somatically mutated cancer antigens, or neoantigens, are now readily identifiable and have become compelling targets for immunotherapy. In particular, neoantigen-targeted vaccines have shown promise in several pre-clinical and clinical studies. However, to date, neoantigen-targeted vaccine studies have involved tumors with exceptionally high mutation burdens. It remains unclear whether neoantigen-targeted vaccines will be broadly applicable to cancers with intermediate to low mutation burdens, such as ovarian cancer. To address this, we assessed whether a derivative of the murine ovarian tumor model ID8 could be targeted with neoantigen vaccines. We performed whole exome and transcriptome sequencing on ID8-G7 cells. We identified 92 somatic mutations, 39 of which were transcribed, missense mutations. For the 17 top predicted MHC class I binding mutations, we immunized mice subcutaneously with synthetic long peptide vaccines encoding the relevant mutation. Seven of 17 vaccines induced robust mutation-specific CD4 and/or CD8 T cell responses. However, none of the vaccines prolonged survival of tumor-bearing mice in either the prophylactic or therapeutic setting. Moreover, none of the neoantigen-specific T cell lines recognized ID8-G7 tumor cells in vitro, indicating that the corresponding mutations did not give rise to bonafide MHC-presented epitopes. Additionally, bioinformatic analysis of The Cancer Genome Atlas data revealed that only 12% (26/220) of HGSC cases had a >=90% likelihood of harboring at least one authentic, naturally processed and presented neoantigen versus 51% (80/158) of lung cancers. Our findings highlight the limitations of applying neoantigen targeted vaccines to tumor types with intermediate/low mutation burdens. PMID- 27192173 TI - LiFE | Literature for ENYGO. PMID- 27192174 TI - Evaluation of the Persistence, Remission, and Emergence of Attention Deficit/Hyperactivity Disorder in Young Adulthood. AB - IMPORTANCE: Attention-deficit/hyperactivity disorder (ADHD) is now recognized to occur in adulthood and is associated with a range of negative outcomes. However, less is known about the prospective course of ADHD into adulthood, the risk factors for its persistence, and the possibility of its emergence in young adulthood in nonclinical populations. OBJECTIVE: To investigate childhood risk factors and young adult functioning of individuals with persistent, remitted, and late-onset young adult ADHD. DESIGN, SETTING, AND PARTICIPANTS: The study sample was the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative birth cohort of 2232 twins born in England and Wales from January 1, 1994, to December 4, 1995. Evaluation of childhood ADHD (ages 5, 7, 10, and 12 years) included prenatal and perinatal factors, clinical characteristics, and aspects of the family environment. Among participants aged 18 years, ADHD symptoms and associated impairment, overall functioning, and other mental health disorders were examined. Data analysis was conducted from February 19 to September 10, 2015. MAIN OUTCOMES AND MEASURES: Attention-deficit/hyperactivity disorder according to DSM-IV diagnostic criteria in childhood and DSM-5 diagnostic criteria in young adulthood. RESULTS: Of 2232 participants in the E Risk Study, 2040 were included in the present analysis. In total, 247 individuals met diagnostic criteria for childhood ADHD; of these, 54 (21.9%) also met diagnostic criteria for the disorder at age 18 years. Persistence was associated with more symptoms (odds ratio [OR], 1.11 [95% CI, 1.04-1.19]) and lower IQ (OR, 0.98 [95% CI, 0.95-1.00]). At age 18 years, individuals with persistent ADHD had more functional impairment (school/work: OR, 3.30 [95% CI, 2.18-5.00], home/with friends: OR, 6.26 [95% CI, 3.07-12.76]), generalized anxiety disorder (OR, 5.19 [95% CI, 2.01-13.38]), conduct disorder (OR, 2.03 [95% CI, 1.03-3.99]), and marijuana dependence (OR, 2.88 [95% CI, 1.07-7.71]) compared with those whose ADHD remitted. Among 166 individuals with adult ADHD, 112 (67.5%) did not meet criteria for ADHD at any assessment in childhood. Results from logistic regressions indicated that individuals with late-onset ADHD showed fewer externalizing problems (OR, 0.93 [95% CI, 0.91-0.96]) and higher IQ (OR, 1.04 [95% CI, 1.02-1.07]) in childhood compared with the persistent group. However, at age 18 years, those with late-onset ADHD demonstrated comparable ADHD symptoms and impairment as well as similarly elevated rates of mental health disorders. CONCLUSIONS AND RELEVANCE: We identified heterogeneity in the DSM-5 young adult ADHD population such that this group consisted of a large, late-onset ADHD group with no childhood diagnosis, and a smaller group with persistent ADHD. The extent to which childhood-onset and late-onset adult ADHD may reflect different causes has implications for genetic studies and treatment of ADHD. PMID- 27192175 TI - PERIPHERAL RETINOPATHY ASSOCIATED WITH APLASTIC ANEMIA. AB - PURPOSE: To report a case of severe, bilateral, rapidly progressing peripheral retinal nonperfusion associated with underlying aplastic anemia. METHODS: An interventional case report. RESULTS: A 4-year-old girl presented with decreased visual acuity. On clinical examination, she was found to have a RAPD, elevated intraocular pressure, 360 degrees rubeosis, vitreous hemorrhage, severe exudative retinal detachment, and telangiectasia with severe peripheral retinal nonperfusion. Laboratory workup was significant for pancytopenia, and a bone marrow biopsy showed extreme hypocellularity with no malignant cells. The patient was diagnosed with primary aplastic anemia. She developed dramatic progression of retinal nonperfusion in the left eye, as well as in the fellow right eye. This bilateral retinopathy was poorly responsive to aggressive management, which included laser photocoagulation and intravitreal injections of anti-vascular endothelial growth factor medications. CONCLUSION: Asymmetric, bilateral quickly progressing peripheral retinal ischemia, in conjunction with pancytopenia and otherwise negative workup may be related to underlying bone marrow failure and aplastic anemia. PMID- 27192176 TI - Prevalence, distribution, and risk factor for colonic neoplasia in 1133 subjects aged 40-49 undergoing screening colonoscopy. AB - BACKGROUND AND AIM: Colorectal cancer (CRC) incidence is rising among <50-year olds. The objective of this study was to determine screening colonoscopy outcomes among 40- to 49-year olds, which are currently limited. METHODS: Asymptomatic 40- to 49-year olds underwent one time CRC screening colonoscopy at The Chinese University of Hong Kong between 2007 and 2011. Screening outcomes, including prevalence, distribution, and predictive factors for overall and specifically proximal colorectal neoplasia were determined. RESULTS: Among 1133 ethnic Chinese, colorectal neoplasia prevalence was 20.5%. In men, distal adenomas were associated with proximal colorectal neoplasia. Men, advancing age, a first degree relative (FDR) with CRC, and diabetes mellitus were independently associated with colorectal neoplasia. A colorectal neoplasia was three times more likely to be found in a 45- to 49-year-old man with FDR of CRC compared with a 40- to 44-year old woman without a FDR of CRC. The numbers needed to screen one colorectal neoplasia, and one advanced neoplasm in the highest risk group of 45- to 49-year old men with FDR with CRC were 2.8 (95% CI: 2.2-4.4) and 18.5 (95% CI: 8.9-39.2), respectively. CONCLUSIONS: Colorectal neoplasia prevalence in this 40- to 49-year old Chinese cohort was higher than previous studies. Men, advancing age, FDR with CRC, and diabetes mellitus, can be used to risk stratify for neoplasia development. Men 45-49 years old with FDR with CRC represented the highest risk subgroup, with the lowest number needed to screen. PMID- 27192178 TI - Minimally adaptive BH: A tiny but uniform improvement of the procedure of Benjamini and Hochberg. AB - We define an adaptive procedure for control of the false discovery rate that is uniformly more powerful than the procedure of Benjamini and Hochberg. The power gain is tiny, however, and only appreciable for small numbers of hypotheses. We illustrate the new method with the case of two hypotheses, for which so far no procedure was known that controls false discovery rate but not also familywise error rate under positive dependence. PMID- 27192179 TI - Current densities and total contact currents during forest clearing tasks under 400 kV power lines. AB - The aim of the study was to analyze all values of electric currents from measured periods while performing tasks in forest clearing. The objective was also to choose and analyze measurement cases, where current measurements successfully lasted the entire work period (about 30 min). Two forestry workers volunteered to perform four forest clearing tasks under 400 kV power lines. The sampling frequency of the current measurements was 1 sample/s. The maximum values of the current densities were 1.0-1.2 mA/m(2) (calculated internal EFs 5.0-12.0 mV/m), and the average values were 0.2-0.4 mA/m(2) . The highest contact current was 167.4 MUA. All measured values during forest clearing tasks were lower than basic restrictions (0.1 V/m and 0.8 V/m) of the International Commission on Non Ionizing Radiation Protection. Bioelectromagnetics. 37:423-428, 2016. (c) 2016 The Authors. Bioelectromagnetics published by Wiley Periodicals, Inc. PMID- 27192180 TI - Fabrication of SnO2 Asymmetric Membranes for High Performance Lithium Battery Anode. AB - Alloy electrode material like tin dioxide (SnO2) possesses much higher specific capacity as compared to commercial graphite anode in lithium ion battery (783 vs 372 mAh g(-1)). However, the huge volume change (260%) of SnO2-based anode during the alloying and dealloying process can cause significant electrode pulverization and rapid capacity loss. Herein we report the synthesis of SnO2 asymmetric membranes via a unique combination of phase inversion and sol-gel chemistry to overcome this big challenge. The SnO2 asymmetric membrane electrode demonstrates a specific capacity of 500 mAh g(-1) based on the overall electrode mass at a current density of 280 mA g(-1) (~0.5C) with >96% capacity retention after 400 cycles. When the current density is increased from 28 to 560 mA g(-1), its overall capacity is only reduced by 36%. Such an outstanding rate and cycling performance is attributed to the existence of networking porous structure in the membrane that can provide high electrical conductivity, multiple diffusion channels, and free volumes for electrode expansion. The carbonization temperature has a dramatic impact on the electrode performance. Membranes carbonized at 500 degrees C show an excellent cycling performance, whereas the capacity of the membrane carbonized at 800 degrees C decreases by 51% in 100 cycles. Such a drastic difference in cycle life is caused by the reduction of small SnO2 NPs (~3.9 nm) into large metallic tin spheres (~40 nm) at 800 degrees C. This is the first original report on using asymmetric membrane structure to stabilize an SnO2 based lithium ion battery anode with an excellent electrochemical performance. PMID- 27192177 TI - Dentate nucleus iron deposition is a potential biomarker for tremor-dominant Parkinson's disease. AB - Parkinson's disease (PD) is a heterogeneous neurodegenerative disorder with variable clinicopathologic phenotypes and underlying neuropathologic mechanisms. Each clinical phenotype has a unique set of motor symptoms. Tremor is the most frequent initial motor symptom of PD and is the most difficult symptom to treat. The dentate nucleus (DN) is a deep iron-rich nucleus in the cerebellum and may be involved in PD tremor. In this study, we test the hypothesis that DN iron may be elevated in tremor-dominant PD patients using quantitative susceptibility mapping. Forty-three patients with PD [19 tremor dominant (TD)/24 akinetic rigidity (AR) dominant] and 48 healthy gender- and age-matched controls were recruited. Multi-echo gradient echo data were collected for each subject on a 3.0 T MR system. Inter-group susceptibility differences in the bilateral DN were investigated and correlations of clinical features with susceptibility were also examined. In contrast with the AR-dominant group, the TD group was found to have increased susceptibility in the bilateral DN when compared with healthy controls. In addition, susceptibility was positively correlated with tremor score in drug naive PD patients. These findings indicate that iron load within the DN may make an important contribution to motor phenotypes in PD. Moreover, our results suggest that TD and AR-dominant phenotypes of PD can be differentiated on the basis of the susceptibility of the DN, at least at the group level. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27192182 TI - Quantum Mechanical Investigation of Mode-Specific Tunneling upon Fundamental Excitation in Malonaldehyde. AB - We present a quantum mechanical study of mode-specific tunneling upon fundamental excitation in malonaldehyde with a multidimensional theory that utilizes the saddle-point normal coordinates. We find that a ring-deformation normal mode is as essential as the well-known imaginary-frequency normal mode in the multidimensional investigation. The changes in tunneling splittings upon fundamental excitation are calculated. The results are competitive with those from a recently developed mixed classical-quantum method. Moreover, the results are qualitatively consistent with experiment for about half of all the modes. PMID- 27192181 TI - Genetic variation in Tunisia in the context of human diversity worldwide. AB - OBJECTIVES: North Africa has a complex demographic history of migrations from within Africa, Europe, and the Middle East. However, population genetic studies, especially for autosomal genetic markers, are few relative to other world regions. We examined autosomal markers for eight Tunisian and Libyan populations in order to place them in a global context. MATERIALS AND METHODS: Data were collected by TaqMan on 399 autosomal single nucleotide polymorphisms on 331 individuals from Tunisia and Libya. These data were combined with data on the same SNPs previously typed on 2585 individuals from 57 populations from around the world. Where meaningful, close by SNPs were combined into multiallelic haplotypes. Data were evaluated by clustering, principal components, and population tree analyses. For a subset of 102 SNPs, data from the literature on seven additional North African populations were included in analyses. RESULTS: Average heterozygosity of the North African populations is high relative to our global samples, consistent with a complex demographic history. The Tunisian and Libyan samples form a discrete cluster in the global and regional views and can be separated from sub-Sahara, Middle East, and Europe. Within Tunisia the Nebeur and Smar are outlier groups. Across North Africa, pervasive East-West geographical patterns were not found. DISCUSSION: Known historical migrations and invasions did not displace or homogenize the genetic variation in the region but rather enriched it. Even a small region like Tunisia contains considerable genetic diversity. Future studies across North Africa have the potential to increase our understanding of the historical demographic factors influencing the region. Am J Phys Anthropol 161:62-71, 2016. (c) 2016 The Authors American Journal of Physical Anthropology Published by Wiley Periodicals, Inc. PMID- 27192183 TI - Applied Grant Writing Training for Future Health Communication Researchers: The Health Communication Scholars Program. AB - Health communication faculty face increasing expectations regarding their academic productivity, including the expectation to seek and secure external funding. Doctoral training in health communication that does not fully prepare students for the challenges of securing external funding is doing them a disservice that will make them less competitive for academic positions and less likely to succeed in the academic positions they assume. The purpose of this study is to share the evaluation of a program, the Health Communication Scholars Program (HCSP), designed to train future health communication researchers in the pursuit of external funding. The HCSP includes a grant-writing workshop, requires interdisciplinary graduate student teams to submit applications, and awards funding to top proposals. HCSP participants responding to an evaluation survey (N = 25) had overwhelmingly positive experiences; respondents felt the program provided great value, improved their writing skills, gave them skills to pursue funding in the future, and helped them secure tenure-track faculty positions. The results of this formal evaluation suggest the HCSP is an experience that builds crucial skills and prepares graduate students for the demands they will face as faculty. It is a relatively low-cost, replicable model that merits consideration and adoption at other institutions that hope to provide professional development for doctoral students interested in health communication. PMID- 27192184 TI - Immunohistochemical localization of irisin in skin, eye, and thyroid and pineal glands of the crested porcupine (Hystrix cristata). AB - Irisin was first identified in muscle cells. We detected irisin immunoreactivity in various organs of the crested porcupine (Hystrix cristata). In the epidermis, irisin immunoreactivity was localized mainly in stratum basale, stratum spinosum and stratum granulosum layers; immunoreactivity was not observed in the stratum corneum. In the dermis, irisin was found in the external and internal root sheath, cortex and medulla of hair follicles, and in sebaceous glands. Irisin immunoreactivity was found in the neural retina and skeletal muscle fibers associated with the eye. The pineal and thyroid glands also exhibited irisin immunoreactivity. PMID- 27192186 TI - Topical Olopatadine in the Treatment of Allergic Conjunctivitis: A Systematic Review and Meta-analysis. AB - PURPOSE: To assess the safety and efficacy of topical olopatadine versus placebo and other topical anti-allergic medications in treating allergic conjunctivitis. METHODS: We systematically searched the literature for randomized-controlled trials that included patients with allergic conjunctivitis, compared olopatadine versus placebo or alternative anti-allergic medications, and examined itch, conjunctival hyperemia, composite symptom or sign scores, and/or occurrence of adverse events. We assessed the safety and efficacy of topical olopatadine when compared with placebo or alternative anti-allergic medications using meta analysis. RESULTS: When compared with placebo, topical olopatadine is associated with a pooled-mean difference (MD) in ocular itch of -1.33 (p < 0.00001) and ocular hyperemia of -0.92 (p < 0.00001). When compared with other agents, olopatadine was inferior to alcaftadine on ocular itch (pooled-MD = 0.39; p < 0.00001) but comparable with epinastine and ketotifen. CONCLUSIONS: Topical olopatadine is a safe and effective treatment modality for allergic conjunctivitis, whereas alcaftadine appears to be superior to olopatadine in reducing ocular itch. PMID- 27192185 TI - Aurora-A regulates MCRS1 function during mitosis. AB - The mitotic spindle is made of microtubules (MTs) nucleated through different pathways involving the centrosomes, the chromosomes or the walls of pre-existing MTs. MCRS1 is a RanGTP target that specifically associates with the chromosome driven MTs protecting them from MT depolymerases. MCRS1 is also needed for the control of kinetochore fiber (K-fiber) MT minus-ends dynamics in metaphase. Here, we investigated the regulation of MCRS1 activity in M-phase. We show that MCRS1 is phosphorylated by the Aurora-A kinase in mitosis on Ser35/36. Although this phosphorylation has no role on MCRS1 localization to chromosomal MTs and K-fiber minus-ends, we show that it regulates MCRS1 activity in mitosis. We conclude that Aurora-A activity is particularly important in the tuning of K-fiber minus-ends dynamics in mitosis. PMID- 27192187 TI - Population-Level Effect of Cholera Vaccine on Displaced Populations, South Sudan, 2014. AB - Following mass population displacements in South Sudan, preventive cholera vaccination campaigns were conducted in displaced persons camps before a 2014 cholera outbreak. We compare cholera transmission in vaccinated and unvaccinated areas and show vaccination likely halted transmission within vaccinated areas, illustrating the potential for oral cholera vaccine to stop cholera transmission in vulnerable populations. PMID- 27192188 TI - Increased Tear Film Osmolarity in Systemic Lupus Erythematosus. AB - PURPOSE: To evaluate tear film osmolarity in patients with systemic lupus erythematosus (SLE). METHODS: A total of 55 eyes from 55 patients with SLE and 47 eyes from 47 age- and gender-matched healthy individuals were included in this study. Tear film osmolarity was evaluated with a lab-on-a-chip technique (TearLab; TearLab Corporation, San Diego, CA) in SLE patients in comparison with healthy individuals, and results were correlated to clinically available diagnostic tests for dry eye, such as tear film break-up time (BUT), Schirmer's test, and Ocular Surface Disease Index (OSDI). RESULTS: The mean tear film osmolarity in the SLE patients and healthy individuals was 306.02 +/- 13.27 mOsm/L and 300.74 +/- 9.11 mOsm/L, respectively, which made for a statistically significant difference (p = 0.020). In the SLE group, tear film osmolarity was negatively correlated with the Schirmer's test score and the BUT value (r = 0.295 p = 0.029 and r = 0.347 p = 0.009, respectively), whereas tear film osmolarity was not correlated with OSDI score (r = -0.182 p = 0.183). CONCLUSIONS: This study revealed that tear film hyperosmolarity and abnormal tear film function are associated with SLE. PMID- 27192189 TI - Association of Model for End-Stage Liver Disease Score With Mortality in Emergency General Surgery Patients. AB - IMPORTANCE: Emergency general surgery (EGS) patients have a disproportionate burden of death and complications. Chronic liver disease (CLD) increases the risk of complications following elective surgery. For EGS patients with CLD, long-term outcomes are unknown and risk stratification models do not reflect severity of CLD. OBJECTIVE: To determine whether the Model for End-Stage Liver Disease (MELD) score is associated with increased risk of 90-day mortality following intensive care unit (ICU) admission in EGS patients. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective cohort study of patients with CLD who underwent an EGS procedure based on International Classification of Diseases, Ninth Revision (ICD 9) procedure codes and were admitted to a medical or surgical ICU within 48 hours of surgery between January 1, 1998, and September 20, 2012, at 2 academic medical centers. Chronic liver disease was identified using ICD-9 codes. Multivariable logistic regression was performed. The analysis was conducted from July 1, 2015, to January 1, 2016. MAIN OUTCOMES AND MEASURES: The primary outcome was all-cause 90-day mortality. RESULTS: A total of 13 552 EGS patients received critical care; of these, 707 (5%) (mean [SD] age at hospital admission, 56.6 [14.2] years; 64% male; 79% white) had CLD and data to determine MELD score at ICU admission. The median MELD score was 14 (interquartile range, 10-20). Overall 90-day mortality was 30.1%. The adjusted odds ratio of 90-day mortality for each 10-point increase in MELD score was 1.63 (95% CI, 1.34-1.98). A decrease in MELD score of more than 3 in the 48 hours following ICU admission was associated with a 2.2-fold decrease in 90-day mortality (odds ratio = 0.46; 95% CI, 0.22-0.98). CONCLUSIONS AND RELEVANCE: In this study, MELD score was associated with 90-day mortality following EGS in patients with CLD. The MELD score can be used as a prognostic factor in this patient population and should be used in preoperative risk prediction models and when counseling EGS patients on the risks and benefits of operative intervention. PMID- 27192190 TI - An edge-on charge-transfer design for energy-resolved x-ray detection. AB - As an x-ray beam goes through the human body, it will collect important information via interaction with tissues. Since this interaction is energy sensitive, the state-of-the-art spectral CT technologies provide higher quality images of biological tissues with x-ray energy information (or spectral information). With existing energy-integrating technologies, a large fraction of energy information is ignored in the x-ray detection process. Although the recently proposed photon-counting technology promises to achieve higher image quality at a lower radiation dose, it suffers from limitations in counting rate, performance uniformity, and fabrication cost. In this paper, we focus on an alternative approach to resolve the energy distribution of transmitted x-ray photons. First, we analyze the x-ray attenuation in a silicon substrate and describe a linear approximation model for x-ray detection. Then, we design an edge-on architecture based on the proposed energy-resolving model. In our design, the x-ray-photon-induced charges are transferred sequentially resembling the working process of a CCD camera. Finally, we numerically evaluate the linear approximation of x-ray attenuation and derive the energy distribution of x-ray photons. Our simulation results show that the proposed energy-sensing approach is feasible and has the potential to complement the photon-counting technology. PMID- 27192191 TI - Living Cell Multilifetime Encoding Based on Lifetime-Tunable Lattice-Strained Quantum Dots. AB - A series of functional quantum dots (QDs) with widely tunable near-infrared fluorescence emission (620-750 nm) and lifetime (30-160 ns) were synthesized via lattice strain and showed excellent photo, colloid, pH, and lifetime stabilities. The well-defined targeting QDs were first developed for a living cell multilifetime encoding strategy to track and recognize specified tumor cell clusters dependent on lifetime distribution using fluorescence lifetime imaging microscopy. PMID- 27192192 TI - Seasonality of reproduction of epiphytic bryophytes in flooded forests from the Caxiuana National Forest, Eastern Amazon. AB - This work aimed to recognize the reproductive biology of the epiphytic bryoflora of phorophytes of Virola surinamensis (Rol. ex. Rottb.) Warb. in varzea and igapo forests in the Caxiuana National Forest, to answer the following question: The reproductive period of the bryophyte species is influenced by the environment due the climatic seasonality present in flooded forests, being higher the occurrence of the sexual and asexual reproduction in the rainiest months? The bryophytes were identified and analyzed for the type of reproduction, sexual system and reproductive structures. In total, 502 samples of bryophytes were analyzed, resulting in 54 species, of which 34 were fertile. The comparison of the fertility of the species in different environmental conditions (dry or rainy, and igapo or varzea forest) was assessed using the chi-square test. The fertility of the seven studied species could not be defined by a pattern, considering the forest type and the seasonality. However, two species were associated to the forest type and two further species to the seasonality, showing that, for some bryophyte species, invest in constant fertility may be favoring the maintenance of their populations in tropical forests. PMID- 27192193 TI - Extraction of bioactive compounds and free radical scavenging activity of purple basil (Ocimum basilicum L.) leaf extracts as affected by temperature and time. AB - In the current study, response surface methodology (RSM) was used to assess the effects of extraction time and temperature on the content of bioactive compounds and antioxidant activity of purple basil leaf (Ocimum basilicum L.) extracts. The stability of anthocyanins in relation to temperature, light and copigmentation was also studied. The highest anthocyanin content was 67.40 mg/100 g extracted at 30 degrees C and 60 min. The degradation of anthocyanins with varying temperatures and in the presence of light followed a first-order kinetics and the activation energy was 44.95 kJ/mol. All the extracts exposed to light showed similar half-lives. The extracts protected from light, in the presence of copigments, showed an increase in half-life from 152.67 h for the control to 856.49 and 923.17 h for extract in the presence of gallic acid and phytic acid, respectively. These results clearly indicate that purple basil is a potential source of stable bioactive compounds. PMID- 27192194 TI - Palynological analysis of Dennstaedtiaceae taxa from the Paranaense Phytogeographic Province that produce Trilete spores II: Microlepia speluncae and Pteridium arachnoideum. AB - The spore morphology and wall ultrastructure of Microlepia speluncae and Pteridium arachnoideum from the Paranaense Province were analyzed with LM, SEM and TEM and a comparative analysis was carried out. In both species the spores are covered by a three-dimensional network of threads branched and fused, tangentially arranged to the surface, and some free-end threads are also seen. The species were differentiated by morphology and the frequency of threads fusion and the networks distribution on the surface of the spores. In both species the exospore is two-layered in section, both layers are traversed by single or branched channels. The perispore is three-layered in section: the inner layer is adhered to the exospore, the middle layer is formed of a three-dimensional network of threads and the outer layer is discontinuous. The perispore ultrastructure of Microlepia speluncae was interpreted as formed of helical subunits displayed around a central channel. The spore morphology and perispore ultrastructure allow differentiating Microlepia from Pteridium but also to the other Dennstaedtiaceae genera that grow in the Paranaense Province. The results obtained allow establishing relationships that let us recognize different groups and gave a new reference to get a better knowledge of the family. PMID- 27192195 TI - The influence of fire on the assemblage structure of foraging birds in grasslands of the Serra da Canastra National Park, Brazil. AB - Grasslands are the most threatened physiognomies of the Cerrado biome (Brazilian savanna), a biodiversity hotspot with conservation as a priority. The Serra da Canastra National Park protects the most important remnants of the Cerrado's southern grasslands, which are under strong anthropogenic pressure. The present study describes the structure of bird assemblages that directly use food resources in burned areas, comparing areas affected by natural fire to the areas where controlled fires were set (a management strategy to combat arson). The tested null hypothesis was that different bird assemblages are structured in a similar manner, regardless of the post-fire period or assessed area. Between December/2012 and January/2015, 92 species were recorded foraging in the study areas. The results indicate that both types of burnings triggered profound and immediate changes in bird assemblages, increasing the number of species and individuals. Natural fires exhibited a more significant influence on the structure (diversity and dominance) than prescribed burnings. Nevertheless, all the differences were no longer noticeable after a relatively short time interval of 2-3 months after prescribed burnings and 3-4 after natural fires. The findings may help the understanding of prescribed burnings as a management strategy for bird conservation in grasslands. PMID- 27192196 TI - The effects of coconut oil supplementation on the body composition and lipid profile of rats submitted to physical exercise. AB - This study aims to verify the effects of coconut oil supplementation (COS) in the body composition and lipid profile of rats submitted to physical exercise. The animals (n=6 per group) were randomly assigned to: G1=Sedentary and Non supplemented (Control Group), G2=Sedentary and Supplemented, G3=Exercised and Non supplemented and G4=Exercised and Supplemented. The COS protocol used was 3 mL/Kg of body mass by gavage for 28 days. The physical exercise was the vertical jumping training for 28 days. It was determined the body mass parameters, Lee Index, blood glucose and lipid profile. The COS did not interfere with body mass, but the lean body mass was lower in G3 compared to G2. The final Lee Index classified G1 and G2 as obese (>30g/cm). The lipid profile showed total cholesterol was decreased in G3, LDL-c concentration was decreased in G2, triglycerides, VLDL-c and HDL-c concentrations were increased in G2 and G4 in relation to G1 and G3. The COS decreased LDL-c/HDL-c ratio. In conclusion, the COS associated or not to physical exercise worsen others lipid parameters, like triglycerides and VLDL-c level, showing the care with the use of lipid supplements. PMID- 27192197 TI - Application of modified simplex on the development of a preconcentration system for cadmium determination in sediments, food and cigarettes. AB - A modified simplex algorithm was used to optimize a system of preconcentration for cadmium determination in samples of sediments, cigarettes and food using flame atomic absorption spectrometry. The preconcentration system is based on the sorption of cadmium in a minicolumn packed with Amberlite XAD-2 resin functionalized with 3,4-dihydroxybenzoic acid (DHB). The optimized variables were pH and sampling flow rate and the optimum conditions found for these variables were, respectively 8.7 and 8.8 mL min-1. The developed system showed a preconcentration factor of 15.3, detection limit of 0.49 ug L-1, quantification limit of 1.65 ug L-1 and precision expressed as relative standard deviation (% RSD, n=10) of 5.9. The accuracy of the method was checked by analysis of estuary sediment certified reference material (NIST 1646-1). The cadmium concentrations found in sediment samples ranged from 1.73 and 1.90 ug g-1. In cigarette samples the results were 0.085 and 0.193 ug g-1, and in food samples (coriander and lettuce) the concentrations found of this metal were, respectively, 0.33 and 0.12 ug g-1. PMID- 27192198 TI - A contribution to the identification of charcoal origin in Brazil II - Macroscopic characterization of Cerrado species. AB - The Brazilian Cerrado is the richest savanna in the world. It is also one of the biomes more threatened in the country and a hotspot for conservation priorities. The main causes of deforestation in Cerrado are agricultural practices, livestock and charcoal production. Although charcoal has a minor impact, its consumption represents the deforestation of 16.000 Km2 of the Cerrado. To contribute for the biomes's conservation it is very important to improve forestry supervision. Thus, in this work we present the macroscopic characterization of charcoal from 25 Cerrado's species. We simulate the real conditions of forest controllers by using the magnifications of 10x, 25x and 65x. Likewise, the charcoals micrographs are all of transverse sections due to the larger amount of anatomical information. We also analyzed texture, brightness, vitrification, ruptures and some special features. The species present several differences in their anatomical structure. Although some of them are very unique, this work does not intent to identify charcoals only by macroscopic analyses. But it might give directions to future identification of genera or species. It also provides knowledge for government agents to verify the documents of forestry origin by fast analyzing a sample of charcoal itself. PMID- 27192199 TI - Anti-PGL-1 Positivity as a Risk Marker for the Development of Leprosy among Contacts of Leprosy Cases: Systematic Review and Meta-analysis. AB - BACKGROUND: There is no point of care diagnostic test for infection with M. Leprae or for leprosy, although ELISA anti PGL-1 has been considered and sometimes used as a means to identify infection. METHODS: A systematic review of all cohort studies, which classified healthy leprosy contacts, at entry, according to anti-PGL1 positivity, and had at least one year follow up. The outcome was clinical diagnosis of leprosy by an experienced physician. The meta analysis used a fixed model to estimated OR for the association of PGL-1 positivity and clinical leprosy. A fixed model also estimated the sensibility of PGL-1 positivity and positive predictive value. RESULTS: Contacts who were anti PGL-1 positive at baseline were 3 times as likely to develop leprosy; the proportion of cases of leprosy that were PGL-1 positive at baseline varied but was always under 50%. CONCLUSIONS: Although there is a clear and consistent association between positivity to anti PGL-1 and development of leprosy in healthy contacts, selection of contacts for prophylaxis based on anti PGL1 response would miss more than half future leprosy cases. Should chemoprophylaxis of controls be incorporated into leprosy control programmes, PGL1 appears not to be a useful test in the decision of which contacts should receive chemoprophylaxis. PMID- 27192200 TI - Time-Based Measurement of Personal Mite Allergen Bioaerosol Exposure over 24 Hour Periods. AB - Allergic diseases such as asthma and rhinitis are common in many countries. Globally the most common allergen associated with symptoms is produced by house dust mites. Although the bed has often been cited as the main site of exposure to mite allergens, surprisingly this has not yet been directly established by measurement due to a lack of suitable methods. Here we report on the development of novel methods to determine the pattern of personal exposure to mite allergen bioaerosols over 24-hour periods and applied this in a small field study using 10 normal adults. Air was sampled using a miniature time-based air-sampler of in house design located close to the breathing zone of the participants, co-located with a miniature time-lapse camera. Airborne particles, drawn into the sampler at 2L/min via a narrow slot, were impacted onto the peripheral surface of a disk mounted on the hour-hand of either a 12 or 24 hour clock motor. The impaction surface was either an electret cloth, or an adhesive film; both novel for these purposes. Following a review of the time-lapse images, disks were post-hoc cut into subsamples corresponding to eight predetermined categories of indoor or outdoor location, extracted and analysed for mite allergen Der p 1 by an amplified ELISA. Allergen was detected in 57.2% of the total of 353 subsamples collected during 20 days of sampling. Exposure patterns varied over time. Higher concentrations of airborne mite allergen were typically measured in samples collected from domestic locations in the day and evening. Indoor domestic Der p 1 exposures accounted for 59.5% of total exposure, whereas total in-bed-asleep exposure, which varied 80 fold between individuals, accounted overall for 9.85% of total exposure, suggesting beds are not often the main site of exposure. This study establishes the feasibility of novel methods for determining the time geography of personal exposure to many bioaerosols and identifies new areas for future technical development and clinical applications. PMID- 27192202 TI - Correction: Two Independent Mutations in ADAMTS17 Are Associated with Primary Open Angle Glaucoma in the Basset Hound and Basset Fauve de Bretagne Breeds of Dog. AB - [This corrects the article DOI: 10.1371/journal.pone.0140436.]. PMID- 27192201 TI - Positive Contrast MRI Techniques for Visualization of Iron-Loaded Hernia Mesh Implants in Patients. AB - OBJECT: In MRI, implants and devices can be delineated via susceptibility artefacts. To discriminate susceptibility voids from proton-free structures, different positive contrast techniques were implemented. The purpose of this study was to evaluate a pulse sequence-based positive contrast technique (PCSI) and a post-processing susceptibility gradient mapping algorithm (SGM) for visualization of iron loaded mesh implants in patients. MATERIAL AND METHODS: Five patients with iron-loaded MR-visible inguinal hernia mesh implants were examined at 1.5 Tesla. A gradient echo sequence (GRE; parameters: TR: 8.3ms; TE: 4.3ms; NSA:2; FA:20 degrees ; FOV:350mm2) and a PCSI sequence (parameters: TR: 25ms; TE: 4.6ms; NSA:4; FA:20 degrees ; FOV:350mm2) with on-resonant proton suppression were performed. SGM maps were calculated using two algorithms. Image quality and mesh delineation were independently evaluated by three radiologists. RESULTS: On GRE, the iron-loaded meshes generated distinct susceptibility-induced signal voids. PCSI exhibited susceptibility differences including the meshes as hyperintense signals. SGM exhibited susceptibility differences with positive contrast. Visually, the different algorithms presented no significant differences. Overall, the diagnostic value was rated best in GRE whereas PCSI and SGM were barely "sufficient". CONCLUSION: Both "positive contrast" techniques depicted implanted meshes with hyperintense signal. SGM comes without additional acquisition time and can therefore be utilized in every patient. PMID- 27192203 TI - Refill Adherence in Relation to Substitution and the Use of Multiple Medications: A Nationwide Population Based Study on New ACE-Inhibitor Users. AB - OBJECTIVE: Generic substitution has contributed to economic savings but switching products may affect patient adherence, particularly among those using multiple medications. The aim was to analyse if use of multiple medications influenced the association between switching products and refill adherence to angiotensin converting-enzyme (ACE) inhibitors in Sweden. STUDY DESIGN AND SETTING: New users of ACE-inhibitors, starting between 1 July 2006 and 30 June 2007, were identified in the Swedish Prescribed Drug Register. Refill adherence was assessed using the continuous measure of medication acquisition (CMA) and analysed with linear regression and analysis of covariance. RESULTS: The study population included 42735 individuals whereof 51.2% were exposed to switching ACE-inhibitor and 39.6% used multiple medications. Refill adherence was higher among those exposed to switching products than those not, but did not vary depending on the use of multiple medications or among those not. Refill adherence varied with age, educational level, household income, country of birth, previous hospitalisation and previous cardiovascular diagnosis. CONCLUSION: The results indicate a positive association between refill adherence and switching products, mainly due to generic substitution, among new users of ACE-inhibitors in Sweden. This association was independent of use of multiple medications. PMID- 27192205 TI - Vitamin C status of Canadian adults: Findings from the 2012/2013 Canadian Health Measures Survey. AB - BACKGROUND: Although vitamin C is not produced in the body, it is important for many biochemical and physiological functions. Little is known about the current vitamin C status of Canadians. This study describes the correlates of vitamin C status in a nationally representative sample of adults. DATA AND METHODS: Data are from the 2012/2013 Canadian Health Measures Survey. Plasma vitamin C (L ascorbic acid) concentrations were measured among a fasting subsample of respondents aged 20 to 79 (n = 1,615). Vitamin C status, prevalence of deficiency (plasma vitamin C < 11 MUmol/L), and use of vitamin C-containing supplements were estimated. Multivariate regression models were used to examine associations between vitamin C status and sociodemographic characteristics, smoking, body mass index, supplement use, and consumption of fruit juice and citrus fruit. RESULTS: The mean plasma vitamin C concentration of adults aged 20 to 79 was 53 MUmol/L; fewer than 3% were vitamin C-deficient. Almost 22% took a vitamin C-containing supplement. Concentrations were lower among smokers and people who were obese, and higher among vitamin C supplement users and fruit juice and citrus fruit consumers. Multivariate models showed that supplement use was the strongest and most consistent predictor of vitamin C status; fruit juice and citrus fruit consumption were predictors only among populations with lower vitamin C concentrations (for example, smokers, obese). INTERPRETATION: Few Canadians were vitamin C-deficient. Smokers and people with a higher BMI were most at risk of lower vitamin C concentrations; concentrations were higher among supplement users and consumers of fruit juice and citrus fruit. PMID- 27192206 TI - Alzheimer's disease and other dementias in Canada. AB - This article provides information on Alzheimer's disease and other dementias, using the 2010/2011 Canadian Community Health Survey, the 2011/2012 Survey of Neurological Conditions in Institutions in Canada, and the 2011 Survey on Living with Neurological Conditions in Canada. Among Canadians aged 45 or older, an estimated 0.8% in private households and 45% in long-term residential care facilities had a diagnosis of dementia. Prevalence rose with age. The vast majority of people with dementia in private households received assistance with medical care (81%), housework and home maintenance (83%), meal preparation (88%), emotional support (90%), transportation (92%), and managing care (92%). Among those receiving assistance, 85% relied, at least in part, on family, friends or neighbours. The primary caregiver tended to be a spouse (46%) or an adult child (44%), most of whom were daughters (71%). The majority of primary caregivers lived in the same household (83%) and provided daily care (86%). PMID- 27192207 TI - Mortality from Alzheimer's disease in Canada: A multiple-cause-of-death analysis, 2004 to 2011. AB - Using multiple-cause-of-death data, this study investigates mortality from Alzheimer's disease. From 2004 through 2011, Alzheimer's disease was coded as a cause of 80,868 deaths-more often the underlying than a contributing cause. The rate of Alzheimer's disease deaths was higher for women and older individuals than for men and younger people, and varied considerably by province/territory. Regardless of whether Alzheimer's disease was coded as the underlying or a contributing cause, on average, two other causes were also listed on the death certificate. When Alzheimer's disease was the underlying cause, cardiovascular diseases were most often listed as a contributing cause; when Alzheimer's disease was a contributing cause, cardiovascular diseases were most often listed as the underlying cause. PMID- 27192204 TI - Interferon-gamma Autoantibodies as Predisposing Factor for Nontuberculous Mycobacterial Infection. PMID- 27192208 TI - Optimizing Sampling Strategies for Riverine Nitrate Using High-Frequency Data in Agricultural Watersheds. AB - Understanding linked hydrologic and biogeochemical processes such as nitrate loading to agricultural streams requires that the sampling bias and precision of monitoring strategies be known. An existing spatially distributed, high-frequency nitrate monitoring network covering ~40% of Iowa provided direct observations of in situ nitrate concentrations at a temporal resolution of 15 min. Systematic subsampling of nitrate records allowed for quantification of uncertainties (bias and precision) associated with estimates of various nitrate parameters, including: mean nitrate concentration, proportion of samples exceeding the nitrate drinking water standard (DWS), peak (>90th quantile) nitrate concentration, and nitrate flux. We subsampled continuous records for 47 site year combinations mimicking common, but labor-intensive, water-sampling regimes (e.g., time-interval, stage-triggered, and dynamic-discharge storm sampling). Our results suggest that time-interval sampling most efficiently characterized all nitrate parameters, except at coarse frequencies for nitrate flux. Stage triggered storm sampling most precisely captured nitrate flux when less than 0.19% of possible 15 min observations for a site-year were used. The time interval strategy had the greatest return on sampling investment by most precisely and accurately quantifying nitrate parameters per sampling effort. These uncertainty estimates can aid in designing sampling strategies focused on nitrate monitoring in the tile-drained Midwest or similar agricultural regions. PMID- 27192211 TI - Comparison of methods for quantitating Salmonella enterica Typhimurium and Heidelberg strain attachment to reusable plastic shipping container coupons and preliminary assessment of sanitizer efficacy. AB - Salmonella serovars, one of the leading contributors to foodborne illness and are especially problematic for foods that are not cooked before consumption, such as fresh produce. The shipping containers that are used to transport and store fresh produce may play a role in cross contamination and subsequent illnesses. However, methods for quantitatively attached cells are somewhat variable. The overall goal of this study was to compare conventional plating with molecular methods for quantitating attached representative strains for Salmonella Typhimurium and Heidelberg on reusable plastic containers (RPC) coupons, respectively. We attached Salmonella enterica serovar Typhimurium ATCC 14028 and serovar Heidelberg SL486 (parent and an antibiotic resistant marker strain) to plastic coupons (2.54 cm(2)) derived from previously used shipping containers by growing for 72 h in tryptic soy broth. The impact of the concentration of sanitizer on log reductions between unsanitized and sanitized coupons was evaluated by exposing attached S. Typhimurium cells to 200 ppm and 200,000 ppm sodium hypochlorite (NaClO). Differences in sanitizer effectiveness between serovars were also evaluated with attached S. Typhimurium compared to attached S. Heidelberg populations after being exposed to 200 ppm peracetic acid (PAA). Treatment with NaClO caused an average of 2.73 +/- 0.23 log CFU of S. Typhimurium per coupon removed with treatment at 200 ppm while 3.36 +/- 0.54 log CFU were removed at 200,000 ppm. Treatment with PAA caused an average of 2.62 +/- 0.15 log CFU removed for S. Typhimurium and 1.41 +/- 0.17 log CFU for S. Heidelberg (parent) and 1.61 +/- 0.08 log CFU (marker). Lastly, scanning electron microscopy (SEM) was used to visualize cell attachment and coupon surface topography. SEM images showed that remaining attached cell populations were visible even after sanitizer application. Conventional plating and qPCR yielded similar levels of enumerated bacterial populations indicating a high concordance between the two methods. Therefore, qPCR could be used for the rapid quantification of Salmonella attached on RPC. PMID- 27192210 TI - An Event-Related Potential Study of Social Information Processing in Adolescents. AB - Increased social awareness is a hallmark of adolescence. The primary aim of this event-related potential study was to investigate whether adolescents, in comparison to adults, would show relatively enhanced early neural processing of complex pictures containing socially-relevant information. A secondary aim was to investigate whether there are also gender and age differences in the ways adolescents and adults process social and nonsocial information. We recorded EEGs from 12-17 year-olds and 25-37 year-olds (N = 59) while they viewed pleasant pictures from the International Affective Picture System. We found age-related amplitude differences in the N1 and the LPP, and gender-related differences in the N2 region for socially-relevant stimuli. Social pictures (featuring mostly young children and adults) elicited larger N1s than nonsocial stimuli in adolescents, but not adults, whereas larger LPPs to social stimuli were seen in adults, but not adolescents. Furthermore, in general, males (regardless of age) showed larger N2s to nonsocial than to social images, but females did not. Our results imply that compared to adults, adolescents show relatively greater initial orientation toward social than toward nonsocial stimuli. PMID- 27192209 TI - Evaluation of the Interaction between the Poincianella pyramidalis (Tul.) LP Queiroz Extract and Antimicrobials Using Biological and Analytical Models. AB - Poincianella pyramidalis (Tul.) LP Queiroz (Fabaceae) is an endemic tree of northeastern Brazil, occurring mainly in the Caatinga. Its medicinal use is widespread and is an important therapeutic option against diarrhea, dysentery, and respiratory and urinary infections, among other diseases. In this study we determined the chemical marker and evaluated the interaction between P. pyramidalis extract and a commercial antimicrobial through the use of biological and analytical models. To obtain the extract, an ethanol-water mixture (50:50 v/v) was used as solvent. It was nebulized in a spray dryer using colloidal silicon dioxide as a drying adjuvant. The extract (ENPp) was subjected to HPLC analysis to verify the presence of certain secondary metabolites. The Minimum Inhibitory Concentration (MIC) of the extract against Gram-negative bacteria was determined by broth microdilution and the MIC of synthetic antimicrobial drugs in the presence and absence of the extract. The antioxidant activity of ENPp was evaluated by the DPPH method. The compatibility between the antimicrobial and the extract was evaluated by thermal analysis (TG/DTA). The acute toxicity of the extract was evaluated in vivo in rodents. The results indicate significant additive action of the extract on synthetic antibiotics, considerable antioxidant activity and absence of toxicity. This extract shows high potential for the development of formulations for antimicrobial therapy when used with a vegetable active ingredient. PMID- 27192212 TI - A Real-Time PCR Method to Detect the Population Level of Halovirus SNJ1. AB - Although viruses of haloarchaea are the predominant predator in hypersaline ecosystem, the culture studies about halovirus-host systems are infancy. The main reason is the tradition methodology (plaque assay) for virus-host interaction depends on culturable and susceptible host. Actually, more than 90% of haloarchaea are unculturable. Therefore, it is necessary to establish an approach for detecting the dynamics of virus in hypersaline environment without culture. In this study, we report a convenient method to determine the dynamics of halovirus SNJ1 based on quantitative real-time PCR (qPCR). All findings showed that the qPCR method was specific (single peak in melt curves), accurate (a good linear relationship between the log of the PFU and the Ct values, R2 = 0.99), reproducible (low coefficient of variations, below 1%). Additionally, the physicochemical characteristics of the samples tested did not influence the stability of qPCR. Therefore, the qPCR method has the potential value in quantifying and surveying haloviruses in halophilic ecological system. PMID- 27192213 TI - The crosstalk between gut microbiota and obesity and related metabolic disorders. AB - Obesity and related metabolic diseases are currently a threat to global public health. The occurrence and development of these conditions result from the combined effects of multiple factors. The human gut is a diverse and vibrant microecosystem, and its composition and function are a focus of research in the fields of life science and medicine. An increasing amount of evidence indicates that interactions between the gut microbiota and their genetic predispositions or dietary changes may be key factors that contribute to obesity and other metabolic diseases. Defining the mechanisms by which the gut microbiota influence obesity and related chronic metabolic diseases will bring about revolutionary changes that will enable practitioners to prevent and control metabolic diseases by targeting the gut microbiota. PMID- 27192214 TI - Sensory processing patterns, coping strategies, and quality of life among patients with unipolar and bipolar disorders. AB - OBJECTIVE: To compare sensory processing, coping strategies, and quality of life (QoL) in unipolar and bipolar patients; to examine correlations between sensory processing and QoL; and to investigate the relative contribution of sociodemographic characteristics, sensory processing, and coping strategies to the prediction of QoL. METHODS: Two hundred sixty-seven participants, aged 16-85 years (53.6+/-15.7), of whom 157 had a diagnosis of unipolar major depressive disorder and 110 had bipolar disorder type I and type II, completed the Adolescent/Adult Sensory Profile, Coping Orientations to Problems Experienced, and 12-item Short-Form Health Survey version 2. The two groups were compared with multivariate analyses. RESULTS: The unipolar and bipolar groups did not differ concerning sensory processing, coping strategies, or QoL. Sensory processing patterns correlated with QoL independently of mediation by coping strategies. Correlations between low registration, sensory sensitivity, sensation avoidance, and reduced QoL were found more frequently in unipolar patients than bipolar patients. Higher physical QoL was mainly predicted by lower age and lower sensory sensitivity, whereas higher mental QoL was mainly predicted by coping strategies. CONCLUSION: While age may predict physical QoL, coping strategies predict mental QoL. Future studies should further investigate the impact of sensory processing and coping strategies on patients' QoL in order to enhance adaptive and functional behaviors related to affective disturbances. PMID- 27192215 TI - Awareness of memory deficits is useful to distinguish between depression and mild cognitive impairment in the elderly. AB - OBJECTIVE: To investigate whether the level of awareness of memory deficits is useful for discriminating between major depressive disorder (MDD) and mild cognitive impairment (MCI) in the elderly. METHODS: Sixty-three consecutively referred patients (38 women and 25 men) with memory concerns comprising three groups (clinical control, MDD and MCI) underwent a memory test (Rey Auditory Verbal Learning Test [RAVLT]) and completed the Memory Assessment Complaints Questionnaire (MAC-Q). Level of awareness was estimated by the difference between the MAC-Q score and the score on the fifth presentation of the RAVLT. Memory performance, Mini-Mental State Examination (MMSE) and depressive symptoms (Geriatric Depression Scale [GDS]) were also assessed. RESULTS: The control (n=25), MDD (n=16), and MCI (n=22) groups were similar in age, educational level, and MMSE (p > 0.05). Among the groups, the MDD group had the most memory complaints, whereas the MCI group had the worst objective memory performance. Level of awareness was capable of discriminating between MDD and MCI (p < 0.05), but not between MDD and clinical controls (p > 0.05). MDD subjects tended to underestimate their memory functioning as compared to controls (p < 0.05). CONCLUSION: Level of awareness of memory deficits was significantly useful to discriminate between MCI and MDD, which is a common difficulty faced by clinicians. Future studies with larger samples are needed to confirm these findings. PMID- 27192216 TI - Mental health in medical residents: relationship with personal, work-related, and sociodemographic variables. AB - Objective:: To examine association of sociodemographic characteristics, personality traits, social skills, and work variables with anxiety, depression, and alcohol dependence in medical residents. Methods:: A total of 270 medical residents completed the following self-report instruments: sociodemographic and work questionnaire, Patient Health Questionnaire-4 (PHQ-4), Alcohol Use Disorders Identification Test-3 (AUDIT-3), Revised NEO-Five Factor Inventory (NEO-FFI-R), and Social Skills Inventory (SSI-Del-Prette). Data were analyzed using descriptive statistics and univariate and multivariate logistic regression analyses. Results:: Multivariate analysis showed an association of neuroticism (odds ratio [OR] 2.60, p < 0.001), social skills (OR 0.41, p < 0.01), and number of shifts (OR 1.91, p = 0.03) with anxiety or depression, and of male sex (OR 3.14, p = 0.01), surgical residency (OR 4.40, p = 0.001), extraversion (OR 1.80, p < 0.01), and number of shifts (OR 2.32, p = 0.04) with alcohol dependence. Conclusion:: The findings support a multidetermined nature of mental health problems in medical residents, in addition to providing data that may assist in the design of preventive measures to protect the mental health of this group. PMID- 27192217 TI - A Comprehensive Evaluation of NIPAM Polymer Gel Dosimeters on Three Orthogonal Planes and Temporal Stability Analysis. AB - Polymer gel dosimeters have been proven useful for dose evaluation in radiotherapy treatments. Previous studies have demonstrated that using a polymer gel dosimeter requires a 24 h reaction time to stabilize and further evaluate the measured dose distribution in two-dimensional dosimetry. In this study, the short term stability within 24 h and feasibility of N-isopropylacrylamide (NIPAM) polymer gel dosimeters for use in three-dimensional dosimetry were evaluated using magnetic resonance imaging (MRI). NIPAM gels were used to measure the dose volume in a clinical case of intensity-modulated radiation therapy (IMRT). For dose readouts, MR images of irradiated NIPAM gel phantoms were acquired at 2, 5, 12, and 24 h after dose delivery. The mean standard errors of dose conversion from using dose calibration curves (DRC) were calculated. The measured dose volumes at the four time points were compared with those calculated using a treatment planning system (TPS). The mean standard errors of the dose conversion from using the DRCs were lower than 1 Gy. Mean pass rates of 2, 5, 12, and 24 h axial dose maps calculated using gamma evaluation with 3% dose difference and 3 mm distance-to-agreement criteria were 83.5% +/- 0.9%, 85.9% +/- 0.6%, 98.7% +/- 0.3%, and 98.5% +/- 0.9%, respectively. Compared with the dose volume histogram of the TPS, the absolute mean relative volume differences of the 2, 5, 12, and 24 h measured dose volumes were lower than 1% for the irradiated region with an absorbed dose higher than 2.8 Gy. It was concluded that a 12 h reaction time was sufficient to acquire accurate dose volume using the NIPAM gels with MR readouts. PMID- 27192218 TI - Regulation of Heat Exchange across the Hornbill Beak: Functional Similarities with Toucans? AB - Beaks are increasingly recognised as important contributors to avian thermoregulation. Several studies supporting Allen's rule demonstrate how beak size is under strong selection related to latitude and/or air temperature (Ta). Moreover, active regulation of heat transfer from the beak has recently been demonstrated in a toucan (Ramphastos toco, Ramphastidae), with the large beak acting as an important contributor to heat dissipation. We hypothesised that hornbills (Bucerotidae) likewise use their large beaks for non-evaporative heat dissipation, and used thermal imaging to quantify heat exchange over a range of air temperatures in eighteen desert-living Southern Yellow-billed Hornbills (Tockus leucomelas). We found that hornbills dissipate heat via the beak at air temperatures between 30.7 degrees C and 41.4 degrees C. The difference between beak surface and environmental temperatures abruptly increased when air temperature was within ~10 degrees C below body temperature, indicating active regulation of heat loss. Maximum observed heat loss via the beak was 19.9% of total non-evaporative heat loss across the body surface. Heat loss per unit surface area via the beak more than doubled at Ta > 30.7 degrees C compared to Ta < 30.7 degrees C and at its peak dissipated 25.1 W m(-2). Maximum heat flux rate across the beak of toucans under comparable convective conditions was calculated to be as high as 61.4 W m(-2). The threshold air temperature at which toucans vasodilated their beak was lower than that of the hornbills, and thus had a larger potential for heat loss at lower air temperatures. Respiratory cooling (panting) thresholds were also lower in toucans compared to hornbills. Both beak vasodilation and panting threshold temperatures are potentially explained by differences in acclimation to environmental conditions and in the efficiency of evaporative cooling under differing environmental conditions. We speculate that non-evaporative heat dissipation may be a particularly important mechanism for animals inhabiting humid regions, such as toucans, and less critical for animals residing in more arid conditions, such as Southern Yellow-billed Hornbills. Alternatively, differences in beak morphology and hardness enforced by different diets may affect the capacity of birds to use the beak for non-evaporative heat loss. PMID- 27192219 TI - Sequential Differentiation of Embryonic Stem Cells into Neural Epithelial-Like Stem Cells and Oligodendrocyte Progenitor Cells. AB - BACKGROUND: Recent advances in stem cell technology afford an unlimited source of neural progenitors and glial cells for cell based therapy in central nervous system (CNS) disorders. However, current differentiation strategies still need to be improved due to time-consuming processes, poorly defined culture conditions, and low yield of target cell populations. METHODOLOGY/PRINCIPLE FINDINGS: This study aimed to provide a precise sequential differentiation to capture two transient stages: neural epithelia-like stem cells (NESCs) and oligodendrocytes progenitor cells (OPCs) derived from mouse embryonic stem cells (ESCs). CHIR99021, a glycogen synthase kinase 3 (GSK-3) inhibitor, in combination with dual SMAD inhibitors, could induce ESCs to rapidly differentiate into neural rosette-like colonies, which facilitated robust generation of NESCs that had a high self-renewal capability and stable neuronal and glial differentiation potentials. Furthermore, SHH combined with FGF-2 and PDGF-AA could induce NESCs to differentiate into highly expandable OPCs. These OPCs not only robustly differentiated into oligodendrocytes, but also displayed an increased migratory activity in vitro. CONCLUSIONS/SIGNIFICANCE: We developed a precise and reliable strategy for sequential differentiation to capture NESCs and OPCs derived from ESCs, thus providing unlimited cell source for cell transplantation and drug screening towards CNS repair. PMID- 27192223 TI - Microfiber interferometer with surface plasmon-polariton involvement. AB - We fabricated a microfiber interferometer with surface plasmon-polaritons (SPPs) involvement. Commonly, the SPPs are not involved in interference due to the mismatch momentum and ultrashort propagation distance. In this Letter, an absorber-doped microfiber is utilized for increasing the matched momentum (i.e., their modal projection), and as a result, an SPP is coherent with an end-fire method-stimulated hybrid SPP. A mathematical model is proposed for investigating the modal-projection-caused interference, and its results show that the proposed interferometer is very dependent on the polarization. Confirmation experiments were carried out, and a good agreement between theoretical predictions and experimental results was found. The proposed interferometer will potentially facilitate many SPP studies in directly related fields. PMID- 27192220 TI - PEGylation of Truncated Streptokinase Leads to Formulation of a Useful Drug with Ameliorated Attributes. AB - Streptokinase (SK) remains a favored thrombolytic agent in the developing world as compared to the nearly 10-fold more expensive human tissue-plasminogen activator (tPA) for the dissolution of pathological fibrin clots in myocardial infarction. However, unlike the latter, SK induces systemic activation of plasmin which results in a greater risk of hemorrhage. Being of bacterial origin, it elicits generation of unwanted antibody and has a relatively short half-life in vivo that needs to be addressed to make it more efficacious clinically. In order to address these lacunae, in the present study we have incorporated cysteine residues specifically at the N- and C-termini of partially truncated SK and these were then PEGylated successfully. Some of the obtained derivatives displayed enhanced plasmin resistance, longer half-life (upto several hours), improved fibrin clot-specificity and reduced immune-reactivity as compared to the native SK (nSK). This paves the way for devising next-generation SK-based thrombolytic agent/s that besides being fibrin clot-specific are endowed with an improved efficacy by virtue of an extended in vivo half-life. PMID- 27192224 TI - High-dynamic-range microscope imaging based on exposure bracketing in full-field optical coherence tomography. AB - By applying the proposed high-dynamic-range (HDR) technique based on exposure bracketing, we demonstrate a meaningful reduction in the spatial noise in image frames acquired with a CCD camera so as to improve the fringe contrast in full field optical coherence tomography (FF-OCT). This new signal processing method thus allows improved probing within transparent or semitransparent samples. The proposed method is demonstrated on 3 MUm thick transparent polymer films of Mylar, which, due to their transparency, produce low contrast fringe patterns in white-light interference microscopy. High-resolution tomographic analysis is performed using the technique. After performing appropriate signal processing, resulting XZ sections are observed. Submicrometer-sized defects can be lost in the noise that is present in the CCD images. With the proposed method, we show that by increasing the signal-to-noise ratio of the images, submicrometer-sized defect structures can thus be detected. PMID- 27192221 TI - Subclinical ultrasound synovitis in a particular joint is associated with ultrasound evidence of bone erosions in that same joint in rheumatoid patients in clinical remission. AB - OBJECTIVES: The main aim of this study was to investigate the relationship between ultrasound (US) findings indicative of joint inflammation and US features characterising bone erosions at joint level in patients with rheumatoid arthritis (RA) in clinical remission. METHODS: Twenty-four consecutive patients with RA in clinical remission according to EULAR criteria (DAS28<2.6) underwent a complete clinical assessment. An experienced sonographer blind to the clinical data performed the US examinations to detect and score signs of joint inflammation and bone erosions from second to fifth metacarpophalangeal (MCP) joints of both hands. All joints were scanned both on dorsal and volar aspects. The second and fifth MCP joints were scanned also in lateral aspects. RESULTS: The patients were mainly female (79.2%), with a mean age of 63.2 years +/-12.3 standard deviation (SD) and a mean disease duration of 114.5 months +/-53.9 SD. Half of the patients were rheumatoid factor positive and 45.8% were anti-citrullinated protein antibody positive. A total of 192 MCP joints and 480 aspects were assessed. Of these joints, 105 (54.7%) were found inflamed by grey-scale US, 57 (29.7%) were power Doppler (PD) positive, and bone erosions were detected in 42 (21.7%) joints. PD signal was found in 30 (53.6%) of the 56 eroded aspects and in only 41 (9.7%) out of the 424 aspects without bone erosions. Both the GS and PD mean scores were statistically higher in the joints with US bone erosions compared to those without erosions. CONCLUSIONS: A higher prevalence of PD signal was found in the joints where bone erosions were detected. This is the first study providing evidence supporting the association between US bone erosions and the persistence of subclinical inflammation in RA patients in clinical remission. PMID- 27192222 TI - Emergence of representations through repeated training on pronouncing novel letter combinations leads to efficient reading. AB - Printed text can be decoded by utilizing different processing routes depending on the familiarity of the script. A predominant use of word-level decoding strategies can be expected in the case of a familiar script, and an almost exclusive use of letter-level decoding strategies for unfamiliar scripts. Behavioural studies have revealed that frequently occurring words are read more efficiently, suggesting that these words are read in a more holistic way at the word-level, than infrequent and unfamiliar words. To test whether repeated exposure to specific letter combinations leads to holistic reading, we monitored both behavioural and neural responses during novel script decoding and examined changes related to repeated exposure. We trained a group of Dutch university students to decode pseudowords written in an unfamiliar script, i.e., Korean Hangul characters. We compared behavioural and neural responses to pronouncing trained versus untrained two-character pseudowords (equivalent to two-syllable pseudowords). We tested once shortly after the initial training and again after a four days' delay that included another training session. We found that trained pseudowords were pronounced faster and more accurately than novel combinations of radicals (equivalent to letters). Imaging data revealed that pronunciation of trained pseudowords engaged the posterior temporo-parietal region, and engagement of this network was predictive of reading efficiency a month later. The results imply that repeated exposure to specific combinations of graphemes can lead to emergence of holistic representations that result in efficient reading. Furthermore, inter-individual differences revealed that good learners retained efficiency more than bad learners one month later. PMID- 27192225 TI - Wide-field broadband extreme ultraviolet transmission ptychography using a high harmonic source. AB - High-harmonic generation (HHG) provides a laboratory-scale source of coherent radiation ideally suited to lensless coherent diffractive imaging (CDI) in the EUV and x-ray spectral region. Here we demonstrate transmission extreme ultraviolet (EUV) ptychography, a scanning variant of CDI, using radiation at a wavelength around 29 nm from an HHG source. Image resolution is diffraction limited at 54 nm and fields of view up to ~100 MUm are demonstrated. These results demonstrate the potential for wide-field, high-resolution, laboratory scale EUV imaging using HHG-based sources with potential application in biological imaging or EUV lithography pellicle inspection. PMID- 27192227 TI - Additional peak appearing in the one-photon luminescence of single gold nanorods. AB - We used a confocal laser microscope to investigate the one-photon photoluminescence (PL) of gold antennas. The PL spectra can be precisely fitted to a plasmon-enhanced PL model. For increasing the antenna length, the energy peak position decreases continuously until it reaches a value of 1.7-1.8 eV. For longer antennas and smaller plasmon energies, we observe an additional, persistent shoulder in the PL spectra, which we explain by a Gaussian-shaped peak at DeltaX~1.78-1.79 eV. We attribute this behavior to the opening of an additional decay path for electrons at the gold interband transition edge, which we observe only for long antennas. PMID- 27192226 TI - Bit-efficient, sub-millisecond wavefront measurement using a lock-in camera for time-reversal based optical focusing inside scattering media. AB - Time-reversed ultrasonically encoded optical focusing measures the wavefront of ultrasonically tagged light, and then phase conjugates the tagged light back to the ultrasonic focus, thus focusing light deep inside the scattering media. In previous works, the speed of wavefront measurement was limited by the low frame rates of conventional cameras. In addition, these cameras used most of their bits to represent an informationless background when the signal-to-background ratio was low, resulting in extremely low efficiencies in the use of bits. Here, using a lock-in camera, we increase the bit efficiency and reduce the data transfer load by digitizing only the signal after rejecting the background. With this camera, we obtained the wavefront of ultrasonically tagged light after a single frame of measurement taken within 0.3 ms, and focused light in between two diffusers. The phase sensitivity has reached 0.51 rad even when the SBR is 6*10-4. PMID- 27192228 TI - Broadband and wide-angle light harvesting by ultra-thin silicon solar cells with partially embedded dielectric spheres. AB - We propose a design of crystalline silicon thin-film solar cells (c-Si TFSCs, 2 MUm-thick) configured with partially embedded dielectric spheres on the light injecting side. The intrinsic light trapping and photoconversion are simulated by the complete optoelectronic simulation. It shows that the embedding depth of the spheres provides an effective way to modulate and significantly enhance the optical absorption. Compared to the conventional planar and front sphere systems, the optimized partially embedded sphere design enables a broadband, wide-angle, and strong optical absorption and efficient carrier transportation. Optoelectronic simulation predicts that a 2 MUm-thick c-Si TFSC with half embedded spheres shows an increment of more than 10 mA/cm2 in short circuit current density and an enhancement ratio of more than 56% in light conversion efficiency, compared to the conventional planar counterparts. PMID- 27192229 TI - Broad-bandwidth near-shot-noise-limited intensity noise suppression of a single frequency fiber laser. AB - A significant broad-bandwidth near-shot-noise-limited intensity noise suppression of a single-frequency fiber laser is demonstrated based on a semiconductor optical amplifier (SOA) with optoelectronic feedback. By exploiting the gain saturation effect of the SOA and the intensity feedback loop, a maximum noise suppression of over 50 dB around the relaxation oscillation frequencies and a suppression bandwidth of up to 50 MHz are obtained. The relative intensity noise of -150 dB/Hz in the frequency range from 0.8 kHz to 50 MHz is achieved, which approaches the shot-noise limit. The obtained optical signal-to-noise ratio is more than 70 dB. This near-shot-noise-limited laser source shows important implications for the advanced fields of high-precision frequency stabilization, quantum key distribution, and gravitational wave detection. PMID- 27192230 TI - Photonic nanojet of cylindrical metalens assembled by hexagonally arranged nanofibers for breaking the diffraction limit. AB - We designed a novel cylindrical metalens assembled by hexagonally arranged close contact nanofibers. A near-field focusing nanojet with a full-width at half maximum (FWHM) waist, 26.7% smaller than the Abbe diffraction limit for 532 nm wavelength light, is observed at the bottom of a 1600 nm diameter cylindrical metalens assembled by 160 nm diameter nanofibers irradiated by a plane wave from the top. Using differently sized nanofibers as building blocks to assemble the metalens, the waist size of the produced photonic nanojet in the near-field zone and the lateral resolution of the focus can be flexibly adjusted, simultaneously breaking the diffraction limit. PMID- 27192231 TI - Thermal degradation of ultrabroad bismuth NIR luminescence in bismuth-doped tantalum germanate laser glasses. AB - Because of ultra-broadband luminescence in 1000-1700 nm and consequent applications in fiber amplifier and lasers in the new spectral range where traditional rare earth cannot work, bismuth-doped laser glasses have received rising interest recently. For long-term practical application, thermal degradation must be considered for the glasses. This, however, has seldom been investigated. Here we report the thermal degradation of bismuth-doped germanate glass. Heating and cooling cycle experiments at high temperature reveal strong dependence of the thermal degradation on glass compositions. Bismuth and tantalum lead to the reversible degradation, while lithium can produce permanent irreversible degradation. The degradation becomes worse as lithium content increases in the glass. Absorption spectra show this is due to partial oxidation of bismuth near-infrared emission center. Surprisingly, we notice the emission of bismuth exhibits blueshift, rather than redshift at a higher temperature, and the blueshift can be suppressed by increasing the lithium content. PMID- 27192232 TI - Phase-shift detection in a Fourier-transform method for temperature sensing using a tapered fiber microknot resonator. AB - Phase-shift detection in a fast-Fourier-transform (FFT)-based spectrum analysis technique for temperature sensing using a tapered fiber microknot resonator is proposed and demonstrated. Multiple transmission peaks in the FFT spectrum of the device were identified as optical modes having completed different amounts of round trips within the ring structure. Temperature variation induced phase shifts for each set of peaks were characterized, and experimental results show that different peaks have distinct temperature sensitivities reaching values up to 0.542 rad/ degrees C, which is about 10 times greater than that of a regular adiabatic taper Mach-Zehnder interferometer when using similar phase-tracking schemes. PMID- 27192233 TI - Efficient nonlinear generation of high power, higher order, ultrafast "perfect" vortices in green. AB - We report on efficient nonlinear generation of ultrafast, higher order "perfect" vortices at the green wavelength. Based on Fourier transformation of the higher order Bessel-Gauss (BG) beam generated through the combination of the spiral phase plate and axicon, we have transformed the Gaussian beam of the ultrafast Yb fiber laser at 1060 nm into perfect vortices of power 4.4 W and order up to 6. Using single-pass second-harmonic generation (SHG) of such vortices in 5 mm long chirped MgO-doped, periodically poled congruent LiNbO3 crystal, we have generated perfect vortices at green wavelength (530 nm) with output power of 1.2 W and vortex order up to 12 at a single-pass conversion efficiency of 27%, independent of the orders. This is the highest single-pass SHG efficiency of any optical beams other than Gaussian beams. Unlike the disintegration of higher order vortices due to spatial walk-off effect in birefringent crystals, here, the use of the quasi-phase-matching process enables generation of high-quality vortices, even at higher orders. The green perfect vortices of all orders have temporal and spectral widths of 507 fs and 1.9 nm, respectively, corresponding to a time-bandwidth product of 1.02. PMID- 27192234 TI - Optimal estimator for tomographic fluorescence lifetime multiplexing. AB - We use the model resolution matrix to analytically derive an optimal Bayesian estimator for multiparameter inverse problems that simultaneously minimizes inter parameter cross talk and the total reconstruction error. Application of this estimator to time-domain diffuse fluorescence imaging shows that the optimal estimator for lifetime multiplexing is identical to a previously developed asymptotic time-domain (ATD) approach, except for the inclusion of a diagonal regularization term containing decay amplitude uncertainties. We show that, while the optimal estimator and ATD provide zero cross talk, the optimal estimator provides lower reconstruction error, while ATD results in superior relative quantitation. The framework presented here is generally applicable to other multiplexing problems where the simultaneous and accurate relative quantitation of multiple parameters is of interest. PMID- 27192235 TI - Single frequency MOPA based on Nd:YAG single crystal fiber and rods. AB - We demonstrate a single frequency 1064 nm master oscillator power amplifier (MOPA) system operating in macro-micro pulse scheme. The repetition rate for the macro pulses was 300 Hz with pulse duration of 300 MUs. Micro pulses operated at 25 kHz. The master laser was a single-longitudinal-mode electro-optically Q switched Nd:YAG laser with an output power of 250 mW and pulse duration of 33 ns. Three stages of power amplifiers based on Nd:YAG single crystal fiber and rods were designed. The final output power reached 31.3 W with pulse duration of 30 ns and linewidth of less than 130 MHz. Micro pulse energy of 13.9 mJ was obtained with a peak power of up to 464 kW. The beam quality factors (M2) were measured to be 1.56 and 1.76 in horizontal and vertical directions, respectively. PMID- 27192237 TI - Infrared dielectric properties of low-stress silicon oxide. AB - Silicon oxide thin films play an important role in the realization of optical coatings and high-performance electrical circuits. Estimates of the dielectric function in the far- and mid-infrared regime are derived from the observed transmittance spectrum for a commonly employed low-stress silicon oxide formulation. The experimental, modeling, and numerical methods used to extract the dielectric function are presented. PMID- 27192236 TI - Tapered polysilicon core fibers for nonlinear photonics. AB - We propose and demonstrate a novel approach to obtaining small-core polysilicon waveguides from the silicon fiber platform. The fibers were fabricated via a conventional drawing tower method and, subsequently, tapered down to achieve silicon core diameters of ~1 MUm, the smallest optical cores for this class of fiber to date. Characterization of the material properties have shown that the taper process helps to improve the local crystallinity of the silicon core, resulting in a significant reduction in the material loss. By exploiting the combination of small cores and low losses, these tapered fibers have enabled the first observation of nonlinear transmission within a polycrystalline silicon waveguide of any type. As the fiber drawing method is highly scalable, it opens a route for the development of low-cost and flexible nonlinear silicon photonic systems. PMID- 27192238 TI - Nonlinear absorption and nonlinear refraction in a chemical vapor deposition grown, ultrathin hexagonal boron nitride film. AB - An ultrathin hexagonal boron nitride film is synthesized by a method of chemical vapor deposition. Irradiated by femtosecond laser pulses in the visible spectrum of 400-800 nm, it exhibits multiphoton absorption and positive nonlinear refraction properties. The two-photon and three-photon absorption coefficients are of the order of 10-5 cm W-1 and 10-14 cm3 W-2, respectively. The nonlinear refraction coefficient is as large as ~10-8 cm2 W-1. These nonlinear coefficients lead to figures of merit that meet the material requirements for all optical switching devices. PMID- 27192239 TI - Enabling transistor-like action in photonic crystal waveguides using optical event horizons. AB - We show that dispersion and loss-engineered photonic crystal waveguides can support optical event horizons enabling the manipulation of a strong soliton pulse by a weaker control pulse within a 3 mm waveguide. Depending on the launching frequency of the weak control pulse, both blue and red soliton shifts are observed, while the soliton appears to be delayed by several pulse widths. PMID- 27192240 TI - Simultaneous three-dimensional velocimetry and thermometry in gaseous flows using the stereoscopic vibrationally excited nitric oxide monitoring technique. AB - We present a demonstration of the simultaneous measurement of spatially resolved three-component velocity and temperature in gaseous flow fields using a variant of the vibrationally excited nitric oxide monitoring (VENOM) technique, based on planar laser induced fluorescence and molecular tagging velocimetry methods. Three-component velocity determinations were derived from two-dimensional molecular tagging velocity measurements employing sequential fluorescence image pairs obtained simultaneously by two cameras in stereoscopic configuration. Probing two different rotational states of nitric oxide (X2?, upsilon''=1), produced via fluorescence and collisional quenching from initial excitation to the A Sigma+2 state, for the sequential velocimetry images allows simultaneous determination of the temperature field. Experimental measurements of velocity and temperature across an oblique shock result in mean values within 21 m/s for the three components of velocity and 20 K for planar temperature when compared to oblique shock calculations. PMID- 27192241 TI - Rapid spectrum measurement at 3 MUm over 100 nm wavelength range using mid infrared difference frequency generation source. AB - We demonstrate a broadband rapid scanning light source in the 3-MUm region by using difference frequency generation (DFG). The DFG source consists of a module with quasi-phase-matched LiNbO3 ridge waveguides, a 1-MUm-band wide swept range laser for the pump source, and a 1.5-MUm continuous wave laser for the signal source. The sweep rate and the tuning bandwidth of this source are 20 kHz and 100 nm, respectively. This source enables us to evaluate the temperature dependence of absorbance of methane gas. PMID- 27192242 TI - Sub-80 femtosecond pulses generation from a diode-pumped mode-locked Nd:Ca3La2(BO3)4 disordered crystal laser. AB - We experimentally demonstrated a diode-pumped sub-80 fs Nd:Ca3La2(BO3)4 disordered crystal laser. Pumping by an 808 nm fiber coupled laser diode, stable continuous-wave mode-locked pulses as short as 79 fs were achieved with a semiconductor saturable absorber mirror (SESAM). The ultrashort pulses had a repetition rate of ~98.9 MHz at the central wavelength of about 1068 nm. To the best of our knowledge, this is the first demonstration of sub-100 fs pulses and the shortest mode-locked pulses generated from the Nd3+-doped crystal lasers. PMID- 27192243 TI - Coherence properties of a 2.6-7.5 MUm frequency comb produced as a subharmonic of a Tm-fiber laser. AB - We study the temporal coherence of an ultrabroadband frequency comb produced in a degenerate GaAs optical parametric oscillator (OPO) pumped by a stabilized Tm fiber comb, by observing multiheterodyne beats in the RF domain. We infer that in such a regime the OPO automatically produces a stable frequency comb that is phase and frequency locked to the pump. By varying intracavity dispersion, we achieve a comb spanning 2.6-7.5 MUm at a -20 dB level. Low pump threshold (down to 7 mW), high average power (up to 73 mW), broad spectral coverage, flat spectrum, and high coherence make this comb a source suitable for various applications, foremost dual-comb molecular spectroscopy. PMID- 27192244 TI - Femtosecond laser direct writing of metal microstructure in a stretchable poly(ethylene glycol) diacrylate (PEGDA) hydrogel. AB - The fabrication of three-dimensional (3D) metal microstructures in a synthetic polymer-based hydrogel is demonstrated by femtosecond laser-induced photoreduction. The linear-shaped silver structure of approximately 2 micrometers in diameter is fabricated inside a biocompatible poly(ethylene glycol) diacrylate (PEGDA) hydrogel. The silver structure is observed and confirmed by scanning electron microscopy (SEM) and elemental analysis using energy-dispersive X-ray spectroscopy (EDX). Shrinking and swelling of the fabricated structure is also demonstrated experimentally, which shows the potential of the present method for realizing 3D flexible electronic and optical devices, as well as for fabricating highly integrated devices at submicron scales. PMID- 27192245 TI - Fast method of calculating a photorealistic hologram based on orthographic ray wavefront conversion. AB - A computer-generated hologram based on ray-wavefront conversion can reconstruct photorealistic three-dimensional (3D) images containing deep virtual objects and complicated physical phenomena; however, the required computational cost has been a problem that needs to be solved. In this Letter, we introduce the concept of an orthographic projection in the ray-wavefront conversion technique for reducing the computational cost without degrading the image quality. In the proposed method, plane waves with angular spectra of the object are obtained via orthographic ray sampling and Fourier transformation, and only the plane waves incident on the hologram plane are numerically propagated. We verified this accelerated computational method theoretically and experimentally, and demonstrated optical reconstruction of a deep 3D image in which the effects of occlusions, transmission, refraction, and reflection were faithfully reproduced. PMID- 27192246 TI - High-resolution plasmonic structural colors from nanohole arrays with bottom metal disks. AB - We present transmissive plasmonic structural colors from subwavelength nanohole arrays with bottom metal disks for scaled-up manufacturing by nanoimprint lithography (NIL). Comprehensive theoretical and experimental studies are carried out to understand the specific extraordinary optical transmission behavior of the structures with such bottom metal disks. Distinctive colors covering the entire visible spectrum can be generated by changing the structural dimensions of hole arrays in Ag covered by the metal disks. The plasmonic energy hybridization theory is applied to explain the unstable color output with shallow holes so that a large processing window during NIL could be achieved for mass production. A high-resolution of 127,000 dots per inch is demonstrated with potential applications, including color filters and displays, high-resolution color printing, CMOS color imaging, and anti-counterfeiting. PMID- 27192247 TI - Visualization of acceleration in multiphase fluid interactions. AB - Probing the dynamics of structures in turbid media is important for understanding the internal forces that drive the time evolution of many fluid systems; the breakup of fuel injection sprays is a prime example. We demonstrate a three-pulse configuration for time-gated ballistic imaging, applied to a turbulent, steady spray allowing the acquisition of time-correlated image data. Coupled with targeted region-matching analysis, the detected image triplets are used to generate time-resolved velocity and acceleration vectors representing motion and forces involved in spray development. PMID- 27192248 TI - Linear mode conversion of terahertz radiation into terahertz surface magnetoplasmons on a rippled surface of magnetized n-InSb. AB - A new mechanics of linear mode conversion of terahertz (THz) radiation into THz surface magnetoplasmons on a rippled surface of magnetized n-InSb is proposed. The normally incident THz radiation, polarized in the direction of a ripple wave vector, imparts oscillatory velocity to electrons in the ripple layer. This velocity beats with surface ripple to produce a nonlinear current that resonantly drives the THz surface magnetoplasmons. In the presence of an applied magnetic field, the surface plasmon (SP) mode splits into two modes-an upper mode and a lower mode. The amplitude of the SP for the upper branch mode is higher than that for the lower mode. PMID- 27192249 TI - Solitonization of a dispersive wave. AB - We report the observation of a nonlinear propagation scenario in which a dispersive wave is transformed into a fundamental soliton in an axially varying optical fiber. The dispersive wave is initially emitted in the normal dispersion region and the fiber properties change longitudinally so that the dispersion becomes anomalous at the dispersive wave wavelength, which allows it to be transformed into a soliton. The solitonic nature of the field is demonstrated by solving the direct Zakharov-Shabat scattering problem. Experimental characterization performed in spectral and temporal domains show evidence of the solitonization process in an axially varying photonic crystal fiber. PMID- 27192250 TI - Phase-shifting by means of an electronically tunable lens: quantitative phase imaging of biological specimens with digital holographic microscopy. AB - The use of an electronically tunable lens (ETL) to produce controlled phase shifts in interferometric arrangements is shown. The performance of the ETL as a phase-shifting device is experimentally validated in phase-shifting digital holographic microscopy. Quantitative phase maps of a section of the thorax of a Drosophila melanogaster fly and of human red blood cells have been obtained using our proposal. The experimental results validate the possibility of using the ETL as a reliable phase-shifter device. PMID- 27192251 TI - Fiber Bragg grating laser sensor with direct radio-frequency readout. AB - A fiber Bragg grating (FBG)-coupled ring laser sensor is demonstrated. In the proposed configuration the interrogating source, the sensing head and the readout instrument are integrated in a single fiber-optic device. An FBG inserted within a bidirectional fiber ring couples the two counterpropagating modes of the cavity, generating a splitting of the resonant wavelengths proportional to the FBG reflectivity. When the cavity gain is brought beyond threshold, the two peaks of the split resonances simultaneously lase, leading to a beat note in the emission spectrum whose frequency tracks any small shift of the FBG reflectivity spectrum. Such a beat note can be simply monitored by a frequency counter, without the need for an optical spectrometer, allowing to significantly reduce size and costs of the sensor setup. The sensing performance compares well to the state-of-the-art thermo-mechanical fiber sensors. PMID- 27192252 TI - Nonlinear laser pulse response in a crystalline lens. AB - The propagation characteristics of a spatial Gaussian laser pulse have been studied inside a gradient-index structured crystalline lens with constant-density plasma generated by the laser-tissue interaction. The propagation of the laser pulse is affected by the nonlinearities introduced by the generated plasma inside the crystalline lens. Owing to the movement of plasma species from a higher- to a lower-temperature region, an increase in the refractive index occurs that causes the focusing of the laser pulse. In this study, extended paraxial approximation has been applied to take into account the evolution of the radial profile of the Gaussian laser pulse. To examine the propagation characteristics, variation of the beam width parameter has been observed as a function of the laser power and initial beam radius. The cavitation bubble formation, which plays an important role in the restoration of the elasticity of the crystalline lens, has been investigated. PMID- 27192253 TI - Real-time quantitative phase imaging based on transport of intensity equation with dual simultaneously recorded field of view. AB - Since quantitative phase distribution reflects both cellular shapes and conditions from another view, compared to traditional intensity observation, different quantitative phase microscopic methods are proposed for cellular detections. However, the transport of intensity equation-based approach not only presents phase, but also intensity, which attracts much attention. While classical transport of intensity equation needs multi-focal images which often cannot realize simultaneous phase measurement, in this Letter, to break through the limitation, a real-time quantitative phase imaging method using transport of intensity equation is proposed. Two identical CCD cameras are set at the binocular tubes to capture the same field of view but at different focal planes. With a double-frame algorithm assuming that the on-focal image is the average of over- and under-focal information, the proposed method is capable of calculating quantitative phase distributions of samples accurately and simultaneously indicating its potentialities in cellular real-time monitoring. PMID- 27192254 TI - Enhanced spectral sensitivity of a chip-scale photonic-crystal slow-light interferometer. AB - We experimentally demonstrate that the spectral sensitivity of a Mach-Zehnder (MZ) interferometer can be enhanced through structural slow light. We observe a 20-fold resolution enhancement by placing a dispersion-engineered, slow-light, photonic-crystal waveguide in one arm of a fiber-based MZ interferometer. The spectral sensitivity of the interferometer increases roughly linearly with the group index, and we have quantified the resolution in terms of the spectral density of interference fringes. These results show promise for the use of slow light methods for developing novel tools for optical metrology and, specifically, for compact high-resolution spectrometers. PMID- 27192255 TI - Demonstration of flat-band image transmission in optically induced Lieb photonic lattices. AB - We present a simple, yet effective, approach for optical induction of Lieb photonic lattices, which typically rely on the femtosecond laser writing technique. Such lattices are established by judiciously overlapping two sublattices (an "egg-crate" lattice and a square lattice) with different periodicities through a self-defocusing photorefractive medium. Furthermore, taking advantage of the superposition of localized flat-band states inherent in the Lieb lattices, we demonstrate distortion-free image transmission in such two dimensional perovskite-like photonic structures. Our experimental observations find good agreement with numerical simulations. PMID- 27192256 TI - Frequency doubling of Raman fiber lasers with random distributed feedback. AB - This Letter presents what we believe is the first experimental study of frequency doubling of a Raman fiber laser (RFL) with random distributed feedback (RDFB) in an MgO:PPLN crystal. We compared two laser configurations, each with a half-open cavity. The cavity contained either a broadband Sagnac mirror or a narrowband fiber Bragg grating (FBG). We found that spectral broadening in the studied configurations of the RDFB RFLs differed from that found in a conventional RFL with a linear cavity, as well as from each other. We also compared the second harmonic generation (SHG) efficiency for these three types of lasers. The highest SHG efficiency was obtained for the RDFB RFL with the FBG delivering >100 mW power at 654 nm. PMID- 27192257 TI - Effect of induced inner curvature on refractive index sensitivity in internally tilted long-period gratings. AB - A new complete analysis of the effect of induced inner curvature on refractive index (RI) sensitivity in internally tilted long-period gratings (ITLPGs) is presented. The responses in terms of RI sensitivity of a standard LPG and different ITLPGs with curvature values between 15 and 19 m-1 were compared. The analysis suggests first, that the larger the induced curvature, the greater the RI sensitivity; and second, that the RI sensitivity exponentially increases with both the curvature and cladding mode order. RI sensitivity greater than 100 nm RIU-1 can be attained with curvature greater than 25 m-1 for LP06 mode. Conversely, the temperature sensitivity of ITLPGs is comparable to standard LPGs for the considered cladding mode order. PMID- 27192258 TI - Self-referenced waveguide grating sensor. AB - Like any other sensor system, performances of waveguide grating couplers are affected by adverse effects such as noise and drift, mainly limiting the devices' resolution and long-term stability. It is therefore often required to reference the measurement with a secondary, parallel sensor to decrease these undesired influences. Here we present a simple but effective method to self-reference a label-free waveguide grating coupler by partially coating and thereby passivating the sensitive area with an inert layer. The presented waveguide grating chip design offers the advantage of internal self-referencing for adverse effects, such as inherent system instabilities, mechanical disturbance, or temperature drift, without the need of a sacrificial reference channel. PMID- 27192259 TI - Ultrafast axial scanning for two-photon microscopy via a digital micromirror device and binary holography. AB - In this Letter, we present an ultrafast nonmechanical axial scanning method for two-photon excitation (TPE) microscopy based on binary holography using a digital micromirror device (DMD), achieving a scanning rate of 4.2 kHz, scanning range of ~180 MUm, and scanning resolution (minimum step size) of ~270 nm. Axial scanning is achieved by projecting the femtosecond laser to a DMD programmed with binary holograms of spherical wavefronts of increasing/decreasing radii. To guide the scanner design, we have derived the parametric relationships between the DMD parameters (i.e., aperture and pixel size), and the axial scanning characteristics, including (1) maximum optical power, (2) minimum step size, and (3) scan range. To verify the results, the DMD scanner is integrated with a custom-built TPE microscope that operates at 60 frames per second. In the experiment, we scanned a pollen sample via both the DMD scanner and a precision z stage. The results show the DMD scanner generates images of equal quality throughout the scanning range. The overall efficiency of the TPE system was measured to be ~3%. With the high scanning rate, the DMD scanner may find important applications in random-access imaging or high-speed volumetric imaging that enables visualization of highly dynamic biological processes in 3D with submillisecond temporal resolution. PMID- 27192260 TI - Effects of bump/pit on the radiative properties of small particles. AB - We use the particle superposition model to create bumps or pits on the surface of small particles for the purpose of simulating the roughness of the particles. Four different models are introduced to show the bump/pit effect on the radiative properties of the host particle. The results show that surface roughness plays an important role in the light scattering properties of small particles. Different roughened models behave differently. PMID- 27192261 TI - Optical thermometry based on the red upconversion fluorescence of Er3+ in CaWO4:Yb3+/Er3+ polycrystalline powder. AB - Based on the fluorescence intensity ratio method, the temperature-sensing behavior through thermally coupled levels (TCL) of the H11/22 and S3/24 states as well as the sub-levels of the F9/24 state of Er3+ has been studied. The thermometry is observed to be dependent on the pump power for the H11/22 and S3/24 states, leading to an error of more than 20 K at 478 K. By utilizing the sub-levels of the F9/24 state, such a problem could be solved. The maximum sensitivity is about 0.15% K-1 at 298 K. This will provide guidance on selecting appropriate and practical TCL for precisely sensing the temperature. PMID- 27192262 TI - Structured beam diffraction. AB - We report on the observation of a modulated pattern induced by a single laser beam in a polymeric film. In spite of the simple geometrical configuration, the analysis of the far field diffraction pattern allows a sensitive retrieving of the wavelength of the recording beam and of its incidence angle, pointing out the high information content of the recorded spot. A theoretical model is presented which satisfactorily explains the observed behavior. It takes into account the interaction of structured light with structured matter with the same symmetries and spatial modulation frequencies close to each other. This result shows a feature of the interaction between structured light and structured matter which has not been explored yet. PMID- 27192263 TI - Enhanced photoluminescence properties of bismuth sulfide nanocrystals with core shell Ag@SiO2. AB - A novel self-assembled hybrid nanocompound consisting of bismuth sulfide nanocrystals (Bi2S3 NCs) and Ag@SiO2 nanoparticles (NPs) is used to study the enhancement of photoluminescence by localized surface plasmon resonance (LSPR). Ag@SiO2 core-shell NPs were prepared by deposition of silica onto the surface of Ag NPs through the sol gel method and followed by surface modification via 3-aminopropyltriethoxysilane for the coming conjugation with Bi2S3 NCs. We propose the photoluminescence enhancement by the LSPR effect through adjusting the thickness of silica shell and the Ag@SiO2 NP concentration. By modulating the thickness of the silica shell and the concentration of Ag NPs, the maximum enhancement of a 5.7 fold can be reached with the thickness of an SiO2 shell at 22.5 nm. A clear red shift of the emission peaks in the Bi2S3 NCs-Ag@SiO2 NPs hybrid structures is observed. Such a metal-enhanced Bi2S3 quantum dot (QD) fluorescence system may have promising applications in optoelectronic device. PMID- 27192264 TI - Design of a variable-line-spacing grating pattern for spectrometers based on a grating Fresnel device. AB - In this Letter, we propose a variable-line-spacing (VLS) grating pattern for a hybrid diffractive device termed a grating Fresnel (G-Fresnel) lens, which is used in spectrometers to improve spectral resolution over a wide spectral range. The VLS grating pattern disperses light of specific wavelengths with a different angle and position such that the aberration caused by the Fresnel surface can be compensated for. In this manner, high resolution can be achieved over a relatively wide spectral range. The VLS grating pattern is designed based on the least wave-change principle and simulated by ZEMAX. Results reveal that the VLS G Fresnel device allows a subnanometer resolution over a spectral range of 200 nm. PMID- 27192265 TI - Microstructures fabricated by dynamically controlled femtosecond patterned vector optical fields. AB - We have presented and demonstrated a method for the fabrication of various complicated microstructures based on dynamically controlled patterned vector optical fields (PVOFs). We design and generate dynamic PVOFs by loading patterned holograms displayed on the spatial light modulator and moving traces of focuses with different patterns. We experimentally fabricate the various microstructures in z-cut lithium niobate plates. The method we present has some benefits such as no motion of the fabricated samples and high efficiency due to its parallel feature. Moreover, our approach is able to fabricate three-dimensional microstructures. PMID- 27192266 TI - Optical lattice induced by angular momentum and polygonal plasmonic mode. AB - A series of plasmonic devices are proposed to generate multipatterned and two dimensional optical lattices with or without helicity. Both the spin and orbital angular momentum of incident beam together with the excited polygonal plasmonic mode contribute to the formation of optical lattices due to the spin-orbit coupling. The impact of the mode property of incident beams on lattice pattern deforming is also discussed. Due to the compactness and flexible tunability, we believe that this work would facilitate the utilization of optical lattices in various on-chip applications. PMID- 27192267 TI - Compensation of a distorted N-fold orbital angular momentum multicasting link using adaptive optics. AB - By using an adaptive feedback correction technique, we experimentally demonstrate turbulence compensation for free-space four-fold and eight-fold 16-ary quadrature amplitude modulation (16-QAM) carrying orbital angular momentum (OAM) multicasting links. The performance of multicasted OAM beams through emulated atmospheric turbulence and adaptive optics assisted compensation loop is investigated. The experimental results show that the scheme can efficiently compensate for the atmospheric turbulence induced distortions, i.e., reducing power fluctuation of multicasted OAM channels, suppressing inter-channel crosstalk, and improving the bit-error rate (BER) performance. PMID- 27192268 TI - Continuous multigram nanoparticle synthesis by high-power, high-repetition-rate ultrafast laser ablation in liquids. AB - Utilizing a novel laser system consisting of a 500 W, 10 MHz, 3 ps laser source which is fully synchronized with a polygon scanner reaching scanning speeds up to 500 m/s, we explore the possibilities to increase the productivity of nanoparticle synthesis by laser ablation in liquids. By exploiting the high scanning speed, laser-induced cavitation bubbles are spatially bypassed at high repetition rates and continuous multigram ablation rates up to 4 g/h are demonstrated for platinum, gold, silver, aluminum, copper, and titanium. Furthermore, the applicable, ablation-effective repetition rate is increased by two orders of magnitude. The ultrafast ablation mechanisms are investigated for different laser fluences, repetition rates, interpulse distances, and ablation times, while the resulting trends are successfully described by validating a model developed for ultrafast laser ablation in air to hold in liquids as well. PMID- 27192269 TI - Coding/decoding two-dimensional images with orbital angular momentum of light. AB - We investigate encoding and decoding of two-dimensional information using the orbital angular momentum (OAM) of light. Spiral phase plates and phase-only spatial light modulators are used in encoding and decoding of OAM states, respectively. We show that off-axis points and spatial variables encoded with a given OAM state can be recovered through decoding with the corresponding complimentary OAM state. PMID- 27192270 TI - Connection between modeled blackbody radiation and dipole emission in large-area nanostructures. AB - When modeling the emission of light from nanostructures, we typically study either (1) blackbody radiation or (2) dipole emission. For effective analysis, it is important to know how results from these two types of modeling are related. Here, we use Kirchoff's reciprocity to study how interference affects the emissivity and number of emitted blackbody photons from a thin film for varying thickness. Next, we use Lorentz's reciprocity to study how interference modifies the emission rate of a dipole placed within the same film. Finally, to find the connection between these two emission types, we use Kirchoff's and Lorentz's reciprocity simultaneously for an arbitrary three-dimensional large-area nanostructure. We show analytically how the blackbody radiation can be represented as the integrated emission from homogeneously distributed dipoles in the nanostructure. In this case, the dipole moment density is determined by the refractive index of the nanostructure. PMID- 27192271 TI - Probing with randomly interleaved pulse train bridges the gap between ultrafast pump-probe and nanosecond flash photolysis. AB - Despite the long-standing importance of transient absorption (TA) spectroscopy, many researchers remain frustrated by the difficulty of measuring the nanosecond range in a wide spectral range. To address this shortcoming, we propose a TA spectrophotometer in which there is no synchronization between a pump pulse and a train of multiple probe pulses from a picosecond supercontinuum light source, termed the randomly-interleaved-pulse-train (RIPT) method. For each pump pulse, many monochromatized probe pulses impinge upon the sample, and the associated pump-probe time delays are determined passively shot by shot with subnanosecond accuracy. By repeatedly pumping with automatically varying time delays, a TA temporal profile that covers a wide dynamic range from subnanosecond to milliseconds is simultaneously obtained. By scanning wavelength, this single, simple apparatus acquires not only wide time range TA profiles, but also broadband TA spectra from the visible through the near-infrared regions. Furthermore, we present a typical result to demonstrate how the RIPT method may be used to correct for fluorescence, which often pollutes TA curves. PMID- 27192272 TI - Few-photon heterodyne spectroscopy. AB - We perform a high-resolution Fourier transform spectroscopy of optical sources in the few-photon regime based on the phenomenon of two-photon interference in a beam splitter. From the heterodyne interferogram, between test and reference sources, it is possible to obtain the spectrum of the test source relative to that of the reference. The method proves to be a useful asset for spectral characterization of faint optical sources below the range covered by classical heterodyne beating techniques. PMID- 27192273 TI - Observation of localized surface plasmons and hybridized surface plasmon polaritons on self-assembled two-dimensional nanocavities. AB - Large-area patterning of periodic nanostructures using self-assembled nanospheres is of interest for fabricating low-cost plasmonic substrates, such as two dimensional (2D) metallic gratings. Surface plasmon polaritons (SPPs) excited on metallic gratings have applications in biosensors, thin-film photovoltaics, photoelectrochemical cells, and photodetectors. Here we fabricated large-area metallic gratings using nanosphere lithography, and the geometry of gratings was controlled by the sphere size and distance between nanospheres. Both forward and backward propagating SPPs were observed using the grating coupling geometry. Furthermore, we reported the first observation of localized surface plasmons (LSPs) on this large-area metallic grating by both simulation and experimental studies. Such an LSP mode was confined in the 2D nanocavities and was not supported by dielectric gratings with the same 2D geometry. PMID- 27192274 TI - Thermo-optical properties of terbium-aluminum garnet ceramics doped with silicon and titanium. AB - The Verdet constant and thermo-optical characteristics of a Si-doped and Ti-doped terbium aluminum garnet ceramics have been investigated. It is shown that the Verdet constant of the samples is ~40% higher than that of TGG ceramics at 1064 nm. The best samples of Si:TAG have magneto-optical figures of merit more than 1.5 times greater than those of TGG ceramics. Si:TAG is better than TGG ceramics as a medium for high-power Faraday isolators. PMID- 27192275 TI - Few-mode fiber based distributed curvature sensor through quasi-single-mode Brillouin frequency shift. AB - We proposed and demonstrated a few-mode fiber (FMF) based optical-fiber sensor for distributed curvature measurement through quasi-single-mode Brillouin frequency shift (BFS). By central-alignment splicing FMF and single-mode fiber (SMF) with a fusion taper, a SMF-components-compatible distributed curvature sensor based on FMF is realized using the conventional Brillouin optical time domain analysis system. The distributed BFS change induced by bending in FMF has been theoretically and experimentally investigated. The precise BFS response to the curvature along the fiber link has been calibrated. A proof-of-concept experiment is implemented to validate its effectiveness in distributed curvature measurement. PMID- 27192276 TI - Bi-doped fiber amplifier with a flat gain of 25 dB operating in the wavelength band 1320-1360 nm. AB - Bismuth (Bi)-doped phosphosilicate fibers have been fabricated by the modified chemical vapor deposition (MCVD)-solution doping technique under different process conditions. The influence of fabrication conditions on unsaturable loss in fibers has been investigated. Pump wavelength dependent Bi gain has been studied to obtain a flat gain over a wide bandwidth. A diode pumped all-fiber Bi doped amplifier with a flat gain of 25+/-1 dB from 1320-1360 nm (40 nm) has been demonstrated for -10 dBm of input signal power with a noise figure (NF) ranging from 4-6 dB. Moreover, a small signal gain of 29 dB and a NF of 4.5 dB at 1340 nm has been achieved for an input signal power of -30 dBm. PMID- 27192278 TI - Inversion of the topological charge of optical vortices in a coil fiber resonator. AB - In this Letter, we study the propagation of optical vortices (OVs) in a two-coil multimode fiber resonator. We suggest an analytical scheme of solving this problem based on its reduction to one of propagation of OVs in parallel evanescently coupled optical fibers. In the framework of the scalar approximation, we derive expressions for normal modes of the system and study evolution of an OV with an arbitrary topological charge excited at the input end of the resonator. We show that such a coil resonator is able to invert the topological charge of the incoming OV, provided the resonance condition is met. PMID- 27192277 TI - Experimental demonstration of quenched transmission effect of an ultrathin metallic grating. AB - We report on the experimental study of an anomalous transmission effect in ultrathin metallic gratings, where the metal thickness is much thinner than the skin depth. In particular, incident transverse magnetic polarized waves are reflected while incident transverse electric polarized waves are transmitted. This anomalous effect is strongly dependent on the metal thickness and metal width. We systematically investigate and demonstrate the anomalous effect and find the optimized nanostrip thickness and width by introducing a shadow-mask fabrication approach. Our results demonstrate the possibility of developing ultrathin nanostrip based planar metasurfaces with low loss. PMID- 27192279 TI - Watt-level second-harmonic generation at 589 nm with a PPMgO:LN ridge waveguide crystal pumped by a DBR tapered diode laser. AB - A DBR tapered diode laser in continuous wave operation was used to generate second-harmonic radiation at 589 nm in a PPMgO:LN ridge waveguide crystal. An optical output power of 0.86 W at an optical-to-optical and an electrical-to optical efficiency of 42% and 11%, respectively, was achieved. The visible radiation was characterized by a spectral bandwidth DeltanuFWHM of 230 MHz and a beam propagation parameter M1/e22 better than 1.1. The integration of such a system into a housing of a small footprint will enable a portable and highly efficient module featuring a visible output power in the watt level range. PMID- 27192280 TI - Laser damage dependence on the size and concentration of precursor defects in KDP crystals: view through differently sized filter pores. AB - We investigate the laser-induced damage performance at 1064 nm of potassium dihydrogen phosphate (KDP) crystals grown using filters of different pore sizes. The aim is to explore a novel method for understanding laser-matter interactions with regard to physical parameters affecting the ability of damage precursors to initiate damage. By reducing the pore size of filters in continuous filtration growth, we can improve laser damage resistance. Furthermore, we develop a model based on a Gaussian distribution of precursor thresholds and heat transfer to obtain a size distribution of the precursor defects. Smaller size and/or lower concentration of precursor defects could lead to better damage resistance. PMID- 27192282 TI - Improved nonlinear slot waveguides using dielectric buffer layers: properties of TM waves. AB - We propose an improved version of the symmetric metal slot waveguides with a Kerr type nonlinear dielectric core adding linear dielectric buffer layers between the metal regions and the core. Using a finite element method to compute the stationary nonlinear modes, we provide the full phase diagrams of its main transverse magnetic modes as a function of the total power, buffer layer, and core thicknesses that are more complex than the ones of the simple nonlinear metal slot. We show that these modes can exhibit spatial transitions toward specific modes of the new structure as a function of power. We also demonstrate that, for the main modes, the losses are reduced compared to the previous structures, and that they can now decrease with power. Finally, we describe the stability properties of the main stationary solutions using nonlinear FDTD simulations. PMID- 27192281 TI - Effects of backscattering in high-Q, large-area silicon-on-insulator ring resonators. AB - We demonstrate large-area silicon-on-insulator ring resonators with Q values of about 2*106 at critical coupling and 3.6*106 for heavily undercoupled conditions. A model has been developed to understand the impact of waveguide backscattering and subcomponent imperfections on the spectral response of our devices. The model predicts the appearance of signals at ports that would not have them under backscattering-free, ideal-power-splitting conditions. The predictions of our model are shown to match the phenomena observed in our measurements. PMID- 27192283 TI - Convolution approach for beam propagation in random media. AB - A simple formula is derived for predicting transverse intensity distribution of coherent and partially coherent (Schell-model) scalar beams propagating in extended linear isotropic, homogeneous media with given power spectra of refractive index. The examples illustrate how the formula can be applied to different beams propagating in atmospheric and oceanic turbulence. Our result provides deep insight into the light-media interaction process and serves as a convenient analytical and/or numerical tool for analyzing beam propagation problems without performing lengthy evaluations. PMID- 27192284 TI - Extending resolution of scanning optical microscopy beyond the Abbe limit through the assistance of InSb thin layers. AB - The resolution of light imaging is required to extend beyond the Abbe limit to the subdiffraction, or even nanoscale. In this Letter, we propose to extend the resolution of scanning optical microscopy (SOM) beyond the Abbe limit as a kind of subdiffraction imaging technology through the assistance of InSb thin layers due to obvious nonlinear saturation absorption and reversible formation of an optical pinhole channel. The results show that the imaging resolution is greatly improved compared with the SOM itself. This work provides a way to improve the resolution of SOM without changing the SOM itself, but through the assistance of InSb thin layers. This is also a simple and practical way to extend the resolution of SOM beyond the Abbe limit. PMID- 27192285 TI - Quantitative phase imaging of biological cells using spatially low and temporally high coherent light source. AB - In this Letter, we demonstrate quantitative phase imaging of biological samples, such as human red blood cells (RBCs) and onion cells using narrow temporal frequency and wide angular frequency spectrum light source. This type of light source was synthesized by the combined effect of spatial, angular, and temporal diversity of speckle reduction technique. The importance of using low spatial and high temporal coherence light source over the broad band and narrow band light source is that it does not require any dispersion compensation mechanism for biological samples. Further, it avoids the formation of speckle or spurious fringes which arises while using narrow band light source. PMID- 27192286 TI - Enhanced super resolution using Fresnel incoherent correlation holography with structured illumination. AB - The structured illumination (SI) technique has already been well established as a resolution enhancer in many studies and well demonstrated in many optical imaging systems during the past decade. The ability to use the SI in incoherent imaging systems was also introduced, especially in fluorescence microscopy. In this Letter, we propose and demonstrate a new approach to combine the SI technique with the recently innovated motionless incoherent holographic system, called Fresnel incoherent correlation holography (FINCH), in order to enhance the resolution beyond the limits achieved in regular imaging with SI. The results obtained by use of SI-FINCH were compared against regular imaging, regular FINCH and SI-imaging. PMID- 27192287 TI - Compact and stable temporally magnified tomography using a phase-locked broadband source. AB - The temporally magnified tomography system is further improved in terms of resolution and imaging stability. We simplify the system configuration and improve the axial resolution simultaneously by utilizing a stabilized all-fiber broadband source. The highly stable spectrum of the source assisted by a phase locked loop guarantees an improved imaging quality. In addition, the impact of the repetition-rate fluctuation of the source to the system stability is analyzed, which also applies to other temporal imaging systems. Achieving a 90 MUm in-air resolution at 89-MHz A-scan rate and improved stability, we are taking one major step toward the practical application of this new optical tomographic modality. PMID- 27192288 TI - Varying polarization and spin angular momentum flux of radially polarized beams by anisotropic Kerr media. AB - Light fields with structured polarization distribution interacting with structured media will result in many novel optical effects in both the linear and nonlinear regimes. In this work, we report a theoretical investigation of both vectorial self-diffraction behaviors and polarization evolution characteristics of a radially polarized beam induced by anisotropic Kerr nonlinearity. By taking the polarization-orientation dependence of the third-order refractive nonlinearity, we study the far-field vectorial self-diffraction patterns of the radially polarized beam using the vectorial Rayleigh-Sommerfeld formulas. Numerical results reveal that the self-diffraction patterns with a four-fold rotational symmetry exhibit hybrid states of polarization. Moreover, the interaction of radially polarized beams with the anisotropic nonlinear Kerr media leads to the redistribution of the spin angular momentum (SAM) flux in the far field plane. The presented work opens up new avenues for varying polarization and SAM through anisotropic optical nonlinearity. PMID- 27192289 TI - High-repetition-rate laser ignition of fuel-air mixtures. AB - A laser-ignition (LI) method is presented that utilizes a high-repetition-rate (HRR) nanosecond laser to reduce minimal ignition energies of individual pulses by ~10 times while maintaining comparable total energies. The most common LI employs a single nanosecond-laser pulse with energies on the order of tens of millijoules to ignite combustible gaseous mixtures. Because of the requirements of high energy per pulse, fiber coupling of traditional LI systems is difficult to implement in real-world systems with limited optical access. The HRR LI method demonstrated here has an order of magnitude lower per-pulse energy requirement than the traditional single-pulse LI technique, potentially allowing delivery through standard commercial optical fibers. Additionally, the HRR LI approach significantly increases the ignition probability of lean combustible mixtures in high-speed flows while maintaining low individual pulse energies. PMID- 27192290 TI - Non-destructive identification of twisted light. AB - The non-destructive identification of the orbital angular momentum (OAM) is essential to various applications in the optical information processing. Here, we propose and demonstrate experimentally an efficient method to identify non destructively the OAM by using a modified Mach-Zehnder interferometer. Our schemes are applicable not only to the case with integer charges, but also to optical vortices with noninteger charges. Our Letter presents the first experimental demonstration of the non-destructive identification of twisted light with integer or noninteger topological charges, which has potential applications in the OAM-based data transmission for optical communications. PMID- 27192291 TI - Three-dimensional grating nanowires for enhanced light trapping. AB - We propose rationally designed 3D grating nanowires for boosting light-matter interactions. Full-vectorial simulations show that grating nanowires sustain high amplitude waveguide modes and induce a strong optical antenna effect, which leads to an enhancement in nanowire absorption at specific or broadband wavelengths. Analyses of mode profiles and scattering spectra verify that periodic shells convert a normal plane wave into trapped waveguide modes, thus giving rise to scattering dips. A 200 nm diameter crystalline Si nanowire with designed periodic shells yields an enormously large current density of ~28 mA/cm2 together with an absorption efficiency exceeding unity at infrared wavelengths. The grating nanowires studied herein will provide an extremely efficient absorption platform for photovoltaic devices and color-sensitive photodetectors. PMID- 27192292 TI - Waveguide-coupled surface phonon resonance sensors with super-resolution in the mid-infrared region. AB - A waveguide-coupled surface phonon resonance (SPhR) sensor with super-resolution based on Fano resonance (FR) by using a multilayer system within the Kretschmann configuration in the mid-infrared wavelength region is proposed. Due to the coherent interference of the waveguide and the surface phonon polariton modes, the calculated reflectivity spectrum possesses sharp asymmetric FR dips. An ultra small linewidth is formed because of the Fano coupling, and the physical features contribute to a highly efficient nano-sensor for refractive index sensing. The bulk and surface sensitivity by intensities are greatly enhanced relative to those of conventional SPhR sensors. PMID- 27192293 TI - Suppression of backreflection error in resonator integrated optic gyro by the phase difference traversal method. AB - The phase difference traversal (PDT) method is proposed to suppress the backreflection-induced error in resonator integrated optic gyro (RIOG). Theoretical analysis shows that the backreflection-induced zero-bias fluctuation is periodical and sine/cosine-like. By forcing the phase difference between the CW and CCW incident light to traverse the interval [0, 2pi] repeatedly and rapidly enough, the fluctuation can be low-pass filtered and, hence, the backreflection-induced error can be effectively suppressed. A RIOG apparatus is built up, with multi-wave hybrid phase modulation to traverse the phase difference and in-phase modulation to set the operation point. A short-term bias stability of 0.0055 deg/s and a long-term bias stability of 0.013 deg/s are successfully demonstrated which, to the best of our knowledge, are the best results reported to date for the buried-type silica waveguide ring resonator based RIOG. PMID- 27192294 TI - Highly improved reliability of amber light emitting diode with Ca -alpha-SiAlON phosphor in glass formed by gas pressure sintering for automotive applications. AB - Phosphor in glass (PiG) with 40 wt% of Ca-alpha-SiAlON phosphor and 60 wt% of Pb free silicate glass was synthesized and mounted on a high-power blue LED to make an amber LED for automotive applications. Gas pressure sintering was applied after the conventional sintering process was used to achieve fully dense PiG plates. Changes in photoluminescence spectra and color coordination were inspected by varying the thickness of the plates that were mounted after optical polishing and machining. A trade-off between luminous flux and color purity was observed. The commercial feasibility of amber PiG packaged LED, which can satisfy international regulations for automotive components, was successfully demonstrated by examining the practical reliability under 85% humidity at an 85 degrees C condition. PMID- 27192295 TI - Sagnac interferometer hydrogen sensor based on panda fiber with Pt-loaded WO3/SiO2 coating. AB - A highly sensitive optical fiber Sagnac interferometer hydrogen sensor is proposed and demonstrated. The device is fabricated by inserting a segment of panda fiber coated with Pt-loaded WO3/SiO2 into a Sagnac interferometer loop. When Pt/WO3 film is exposed to hydrogen, the exothermic reaction raises the temperature of the panda fiber, resulting in the resonant wavelength shift of the interferometer, and the resonant dip obtained has a large extinction ratio of ~25 dB and a narrow linewidth of 2.5 nm. Such a device responds fast to hydrogen, exhibits a high sensitivity of -7.877 nm/% (vol. %) within the range of 0%-1.0% and is robust, low cost, and easy to fabricate. PMID- 27192296 TI - 266 nm ultraviolet light generation in Ga-doped BaAlBO3F2 crystals. AB - BaAlBO3F2 (BABF) crystals are a recently developed and promising nonlinear optical material, notably for the third harmonic generation of ultraviolet (UV) light at 355 nm. However, the fourth harmonic generation of UV light at 266 nm has never been obtained by using a BABF crystal due to its relatively small birefringence. We demonstrate that the birefringence of BABF can be effectively increased by doping it with Ga3+. The fourth harmonic generation of UV light at 266 nm was achieved for the first time in a Ga-doped BABF crystal. PMID- 27192297 TI - High-power continuous-wave dual-wavelength operation of a diode-pumped Yb:KGW laser. AB - High-power dual-wavelength diode-pumped Yb:KGW laser using a single birefringent filter plate was demonstrated. Two oscillating wavelengths maintained the same polarization and stable dual-wavelength operation at 1014.6 and 1041.3 nm (7.57 THz of frequency offset) with 3.4 W of average output power and a diffraction limited beam profile was obtained. Dual-wavelength laser operation at shorter- or longer-wavelength pairs with lower average output power could also be realized for other output-coupling transmissions. PMID- 27192298 TI - Ultrafast rotating dipole or propeller-shaped patterns: subwavelength shaping of a beam of light on a femtosecond time scale. AB - We report on a remarkable property of azimuthally (radially) polarized light beams containing a vortex or an orbital angular momentum: upon tight focusing of a first-order vortex beam, the subwavelength spot has a shape of an electric (magnetic) dipole rotating at an optical frequency. For beams with a vortex of order m, the generated pattern is propeller-shaped and rotates at a 1/m fraction of the optical frequency. The applications include petahertz control of electrical or optical conductance between two electrodes or waveguides of two terminal junctions. PMID- 27192299 TI - 110 W 1678 nm laser based on high-efficiency optical parametric interactions pumped by high-power slab laser. AB - This Letter presents a high-efficiency optical parametric amplifier pumped by a high-power slab laser with approximate uniform rectangular distribution. By optimizing the overlapping, spectrum matching, and pulse synchronization for the pump and signal lasers, output power of 110.8 W at 1678 nm with corresponding conversion efficiency of 32.3% was achieved in addition to sufficient usage of the effective area in MgO doped periodically poled lithium niobate crystal. It could also provide a designable and tunable wavelength of the amplified laser in a wide infrared region. PMID- 27192300 TI - Ultra-sensitive cavity ring-down spectroscopy in the mid-infrared spectral region. AB - We describe an ultra-sensitive cavity ring-down spectrometer which operates in the mid-infrared spectral region near 4.5 MUm. With this instrument a noise equivalent absorption coefficient of 2.6*10-11 cm-1 Hz-1/2 was demonstrated with less than 150 nW of optical power incident on the photodetector. Quantum noise was observed in the individual ring down decay events, leading to quantum-noise-limited short-time performance. We believe that this spectrometer's combination of high sensitivity and robustness make it well suited for measurements of ultra-trace gas species as well as applications in optics and fundamental physics. PMID- 27192301 TI - Phase retrieval by using the transport-of-intensity equation with Hilbert transform. AB - Phase recovery by solving the transport-of-intensity equation (TIE) is a non iterative and non-interferometric phase retrieval technique. From solving the TIE with conventional, one partial derivative and Hilbert transform methods for both the periodic and aperiodic samples, we demonstrate that the Hilbert transform method can provide the smoother phase images with edge enhancement and fine structures. Furthermore, compared with the images measured by optical and atomic force microscopy, the Hilbert transform method has the ability to quantitatively map out the phase images for both the periodic and aperiodic structures. PMID- 27192302 TI - Transmission of three-polarization-multiplexed 25-Gb/s DPSK signals over 300-km fiber link. AB - Polarization is one of the key parameters to be utilized for large capacity and high spectral-efficient optical communication systems, especially the widely deployed polarization-division-multiplexing (PDM) scheme. To break the limitation of only two orthogonal polarization states that could be used for carrying data signals over the same wavelength, we experimentally demonstrate the first transmission of three-polarization-division-multiplexed DPSK signals at a rate up to 3*25 Gb/s over 300-km fiber link by using a single-carrier. PMID- 27192303 TI - Majorization applied to diffraction. AB - We apply the statistical tools of majorization to characterize and compare the amount of diffraction caused by different apertures, where variance cannot be applied. PMID- 27192304 TI - Yb:YAG single-crystal fiber amplifiers for picosecond lasers using the divided pulse amplification technique. AB - A two-stage master-oscillator power-amplifier (MOPA) system based on Yb:YAG single-crystal-fiber (SCF) technology and designed for high peak power is studied to significantly increase the pulse energy of a low-power picosecond laser. The first SCF amplifier has been designed for high gain. Using a gain medium optimized in terms of doping concentration and length, an optical gain of 32 dB has been demonstrated. The second amplifier stage designed for high energy using the divided pulse technique allows us to generate a recombined output pulse energy of 2 mJ at 12.5 kHz with a pulse duration of 6 ps corresponding to a peak power of 320 MW. Average powers ranging from 25 to 55 W with repetition rates varying from 12.5 to 500 kHz have been demonstrated. PMID- 27192305 TI - Enhancement of radiative processes in nanofibers with embedded plasmonic nanoparticles. AB - Efficient manipulation and long-distance transport of single photons is a key component in nanoscale quantum optics. In this Letter, we study the emission properties of an individual light emitter placed into a nanofiber and coupled to a metallic nanoparticle. We find that plasmonic field enhancement together with nanofiber optical confinement uniquely and synergistically contribute to an overall increase of emission rates as well as quantum yields. We predict a quantum yield enhancement up to a factor of 2.5 with respect to free space for an averaged dipole orientation. PMID- 27192306 TI - Optically integrated trimodality imaging system: combined all-optical photoacoustic microscopy, optical coherence tomography, and fluorescence imaging. AB - We have developed a trimodality imaging system by optically integrating all optical photoacoustic microscopy (AOPAM), optical coherence tomography (OCT), and fluorescence microscopy (FLM) to provide complementary information including optical absorption, optical back-scattering, and fluorescence contrast of biological tissue. By sharing the same low-coherence Michelson interferometer, AOPAM and OCT could be organically optically combined. Also, owing to using the same laser source and objective lens, intrinsically registered photoacoustic and fluorescence signals are obtained in a single pulse. Simultaneously photoacoustic angiography, tissue structure, and fluorescence molecular in vivo images of mouse ear were acquired to demonstrate the capabilities of the optically integrated trimodality imaging system, which can present more information to study tumor angiogenesis, vasculature, anatomical structure, and microenvironments in vivo. PMID- 27192307 TI - High-temperature flow field's electron number density measurement by two wavelength moire tomography. AB - In this Letter, a direct method is proposed to measure the electron number density distribution for high-temperature complex flow fields. The experimental system of two-wavelength moire tomography is established, while four key issues are solved and well clarified. The argon arc plasma is adopted as an example for experiment, while 532 and 808 nm are chosen as the two probe wavelengths. The results indicate that the electron number density's distribution of the measured argon arc plasma can be directly obtained by two-wavelength moire tomography, which can avoid the imprecision of the indirect methods. This Letter can provide some reference for various high-temperature and high-density gradient flow field optical measurement and diagnosis. PMID- 27192308 TI - Simultaneous multi-frequency topological edge modes between one-dimensional photonic crystals. AB - We show theoretically that, in the limit of weak dispersion, one-dimensional binary centrosymmetric photonic crystals can support topological edge modes in all photonic bandgaps. By analyzing their bulk band topology, these "harmonic" topological edge modes can be designed in a way that they exist at all photonic bandgaps opened at the center of the Brillouin zone, at all gaps opened at the zone boundaries, or both. The results may suggest a new approach to achieve robust multi-frequency coupled modes for applications in nonlinear photonics, such as frequency upconversion. PMID- 27192309 TI - Subwavelength-grating-assisted broadband polarization-independent directional coupler. AB - This Letter presents both numerical and experimental results of a polarization independent directional coupler based on slot waveguides with a subwavelength grating. The measured coupling efficiency is 97.4% for TE and 96.7% for TM polarization at a wavelength of 1550 nm. Further analysis shows that the proposed subwavelength grating directional coupler has a fabrication tolerance of +/-20 nm for the grating structure and that the coupling efficiencies for the two polarizations are both higher than -0.5 dB (~89%), exceeding the entire C-band (1525-1570 nm) experimentally. PMID- 27192310 TI - Trapping and manipulating nanoparticles in photonic nanojets. AB - A novel optical manipulation system based on photonic nanojets (PNJs) is numerically investigated based on the finite element method. It is found that nanoscale particles can be trapped stably in a standing-wave PNJ generated by the constructive interference between two coherent PNJs. In particular, we show that the elongated standing-wave PNJs generated by using two-layer microcylinders or microspheres can provide larger manipulation platforms and stronger optical forces. To assess the trapping stability of the particle under the Brownian motion in the elongated PNJ, the relationship between the stability number and the particle size is studied. The simulation results show that the proposed elongated standing-wave PNJs can provide the stable and tunable manipulation for dielectric nanoparticles that are smaller than 100 nm. PMID- 27192311 TI - Pushing phase and amplitude sensitivity limits in interferometric microscopy. AB - Sensitivity of the amplitude and phase measurements in interferometric microscopy is influenced by factors such as instrument design and environmental interferences. Through development of a theoretical framework followed by experimental validation, we show photon shot noise is often the limiting factor in interferometric microscopy measurements. Thereafter, we demonstrate how a state-of-the-art camera with million-level electrons full well capacity can significantly reduce shot noise contribution resulting in a stability of optical path length down to a few picometers even in a near-common-path interferometer. PMID- 27192312 TI - Sum frequency generation of UV laser radiation at 266 nm in LBO crystal. AB - We report experimental results of generation at 266 nm in LBO crystal by frequency mixing of the fundamental (1064 nm) and third harmonic (355 nm) of ytterbium pulsed fiber laser radiation. Deep ultraviolet (DUV) output power of 3.3 W at 266 nm was achieved with 14% IR-to-DUV conversion efficiency. UV-induced bulk degradation of LBO crystals was observed and visualized by the dark field method. PMID- 27192313 TI - Optically pumped 1.3 MUm room-temperature InAs quantum-dot micro-disk lasers directly grown on (001) silicon. AB - Direct integration of high-performance laser diodes on silicon will dramatically transform the world of photonics, expediting the progress toward low-cost and compact photonic integrated circuits (PICs) on the mainstream silicon platform. Here, we report, to the best of our knowledge, the first 1.3 MUm room-temperature continuous-wave InAs quantum-dot micro-disk lasers epitaxially grown on industrial-compatible Si (001) substrates without offcut. The lasing threshold is as low as hundreds of microwatts, similar to the thresholds of identical lasers grown on a GaAs substrate. The heteroepitaxial structure employed here does not require the use of an absorptive germanium buffer and/or dislocation filter layers, both of which impede the efficient coupling of light from the laser active regions to silicon waveguides. This allows for full compatibility with the extensive silicon-on-insulator (SOI) technology. The large-area virtual GaAs (on Si) substrates can be directly adopted in various mature in-plane laser configurations, both optically and electrically. Thus, this demonstration represents a major advancement toward the commercial success of fully integrated silicon photonics. PMID- 27192314 TI - Spontaneous generation of singularities in paraxial optical fields. AB - In nonrelativistic quantum mechanics, the spontaneous generation of singularities in smooth and finite wave functions is a well understood phenomenon also occurring for free particles. We use the familiar analogy between the two dimensional Schrodinger equation and the optical paraxial wave equation to define a new class of square-integrable paraxial optical fields that develop a spatial singularity in the focal point of a weakly focusing thin lens. These fields are characterized by a single real parameter whose value determines the nature of the singularity. This novel field enhancement mechanism may stimulate fruitful research for diverse technological and scientific applications. PMID- 27192315 TI - Current sensing using circularly birefringent twisted solid-core photonic crystal fiber. AB - Continuously twisted solid-core photonic crystal fiber (PCF) exhibits pure circular birefringence (optical activity), making it ideal for current sensors based on the Faraday effect. By numerical analysis, we identify the PCF geometry for which the circular birefringence (which scales linearly with twist rate) is a maximum. For silica-air PCF, this occurs at a shape parameter (diameter-to spacing ratio of the hollow channels) of 0.37 and a scale parameter (spacing-to wavelength) of 1.51. This result is confirmed experimentally by testing a range of different structures. To demonstrate the effectiveness of twisted PCF as a current sensor, a length of fiber is placed on the axis of a 7.6 cm long solenoid, and the Faraday rotation is measured at different values of dc current. The system is then used to chart the wavelength dependence of the Verdet constant. PMID- 27192316 TI - Versatile and widely tunable mid-infrared erbium doped ZBLAN fiber laser. AB - We report on a long wavelength emitting rare earth doped fiber laser with the emission centered at 3.5 MUm and tunable across 450 nm. The longest wavelength emission was 3.78 MUm which is the longest emission from a fiber laser operating at room temperature. In a simple optical arrangement employing dielectric mirrors for feedback, the laser was capable of emitting 1.45 W of near diffraction limited output power at 3.47 MUm. These emission characteristics complement the emissions from quantum cascade lasers and demonstrate how all infrared dual wavelength pumping can be used to access high lying rare earth ion transitions that have previously relied on visible wavelength pumping. PMID- 27192317 TI - Novel thin-disk oscillator concept for the generation of radially polarized femtosecond laser pulses. AB - We report on the first demonstration of a radially polarized passively mode locked thin-disk oscillator. Radial polarization was achieved by the use of a novel circular grating waveguide output coupler. We showed mode-locked operation up to a maximum average output power of 13.3 W with an optical efficiency of 21.8%. The degree of radial polarization of the emitted beam was measured to be 97+/-1%. The laser system generated pulses with a duration of 907 fs and an energy of 316 nJ corresponding to a peak power of 0.35 MW. To the best of our knowledge, these values exceed the performance of previously reported radially polarized mode-locked oscillator systems. PMID- 27192318 TI - Focusing surface plasmon polaritons and detecting Stokes parameters utilizing nanoslits distributed plasmonic lenses. AB - A method to detect the full Stokes parameters utilizing a double-ring and Archimedes-curves distributed nanoslits plasmonic lenses is proposed. We demonstrate theoretically and numerically that both of these two plasmonic lenses can focus surface plasmon polaritons to centrally symmetric fields with subwavelength-sized focal spots under linear, elliptical, and circular polarization incidence. The intensity at the focal spots is modulated by the polarization state of incident light. Utilizing this intensity polarization sensitivity, the full Stokes parameters of incident light are detected by recoding only four intensities at the focal spots of these two plasmonic lenses. PMID- 27192319 TI - Measuring chromatic aberrations in imaging systems using plasmonic nanoparticles. AB - We demonstrate a method to measure chromatic aberrations of microscope objectives with metallic nanoparticles using white light. Extinction spectra are recorded while scanning a single nanoparticle through a lens's focal plane. We show a direct correlation between the focal wavelength and the longitudinal chromatic focal shift through our analysis of the variations between the scanned extinction spectra at each scan position and the peak extinction over the entire scan. The method has been tested on achromat and apochromat objectives using aluminum disks varying in size from 260-520 nm. Our method is straightforward, robust, low cost, and broadband with a sensitivity suitable for assessing longitudinal chromatic aberrations in high-numerical-aperture apochromatic corrected lenses. PMID- 27192320 TI - Reflection-induced linear polarization rotation and phase modulation between orthogonal waves for refractive index variation measurement. AB - An optical phase interrogation is proposed to study reflection-induced linear polarization rotation in a common-path homodyne interferometer. This optical methodology can also be applied to the measurement of the refractive index variation of a liquid solution. The performance of the refractive index sensing structure is discussed theoretically, and the experimental results demonstrated a very good ability based on the proposed schemes. Compared with a conventional common-path heterodyne interferometer, the proposed homodyne interferometer with only a single channel reduced the usage of optic elements. PMID- 27192321 TI - Synthesis of Polysubstituted Benzoic Esters from 1,2-Dihydropyridines and Its Application to the Synthesis of Fluorenones. AB - A convenient, instrumentally simple, and efficient methodology to transform 1,2 dihydropyridines into benzoic esters is described. The generated multisubstituted benzoic esters feature different topologies spanning from simple aromatic rings to fused benzocycloalkane systems. As an extension of this methodology, these benzoic esters are efficiently transformed into an array of fluorenone frameworks featuring interesting and novel topological patterns. PMID- 27192322 TI - Drug therapies for HIV-related metabolic disorders. AB - INTRODUCTION: Human immunodeficiency virus (HIV) has become a chronic disease often associated with dyslipidaemia and insulin resistance. Combination antiretroviral therapy (cART) may contribute to metabolic disturbances, eventually leading to increased cardiovascular disease (CVR) in this population. Escalating interventions to decrease CVR include promoting a healthy lifestyle, such as quitting smoking, diet and regular exercise. If they do not achieve the goals, a change of cART should be considered, followed by or used concomitantly with the use of chemical therapies. AREAS COVERED: The aim of this article is to review the available drug therapies for the treatment of metabolic disorders in HIV-infected patients and to examine their safety and effectiveness in this population. A review of the literature was conducted, highlighting the most relevant articles. EXPERT OPINION: Switching strategies can be useful but its expected benefit is not high. Therefore, chemical intervention is often needed. Statins have been proven to reduce CVR in the general population and in HIV infected patients. Simvastatin is contraindicated in patients treated with boosted PI due to interactions; atorvastatin is safe at submaximal dose and needs close monitoring, while pravastatin lacks lipid-lowering potency, and rosuvastatin and pitavastatin are safe. Ezetimibe and fibrates are also safe and effective in HIV-infected patients and can be used in combination with statins. The management of glucose homeostatic disorders in HIV-infected patients follows the same guidelines as in the general population. However, there are specific considerations with respect to the interactions of particular medications with cART. When drug therapy is needed, metformin is the first-line drug. Decisions regarding second- and third-line drugs should be carefully individualized. PMID- 27192324 TI - Size-Selective Nanoparticle Assembly on Substrates by DNA Density Patterning. AB - The vision of nanoscale self-assembly research is the programmable synthesis of macroscale structures with controlled long and short-range order that exhibit a desired set of properties and functionality. However, strategies to reliably isolate and manipulate the nanoscale building blocks based on their size, shape, or chemistry are still in their infancy. Among the promising candidates, DNA mediated self-assembly has enabled the programmable assembly of nanoparticles into complex architectures. In particular, two-dimensional assembly on substrates has potential for the development of integrated functional devices and analytical systems. Here, we combine the high-resolution patterning capabilities afforded by electron-beam lithography with the DNA-mediated assembly process to enable direct write grayscale DNA density patterning. This method allows modulation of the functionally active DNA surface density to control the thermodynamics of interactions between nanoparticles and the substrate. We demonstrate that size selective directed assembly of nanoparticle films from solutions containing a bimodal distribution of particles can be realized by exploiting the cooperativity of DNA binding in this system. To support this result, we study the temperature dependence of nanoparticle assembly, analyze the DNA damage by X-ray photoelectron spectroscopy and fluorescence microscopy, and employ molecular dynamics simulations to explore the size-selection behavior. PMID- 27192325 TI - Electron Transfer Facilitated by Dendrimer-Encapsulated Pt Nanoparticles Across Ultrathin, Insulating Oxide Films. AB - Electrocatalytic oxygen reduction at carbon electrodes fully passivated by Al2O3 is reported. Specifically, pyrolyzed polymer film (PPF) electrodes were prepared and then coated with pinhole-free Al2O3 layers ranging in thickness from 2.5 to 5.7 nm. All of these ultrathin oxide film thicknesses completely passivated the PPF electrodes, resulting in no faradaic current for either inner-sphere or outer sphere electrochemical reactions. The electrodes could, however, be reactivated by immobilizing Pt dendrimer-encapsulated nanoparticles (DENs), containing an average of 55 atoms each, on the oxide surface. These PPF/Al2O3/Pt DEN electrodes were completely stable under a variety of electrochemical and solution conditions, and they are active for simple electron-transfer reactions and for more complex electrocatalytic processes. This approach for preparing well-defined oxide electrodes opens the door to a better understanding of the effect of oxide supports on reactions electrocatalyzed by metal nanoparticles. PMID- 27192323 TI - Ratiometric Tension Probes for Mapping Receptor Forces and Clustering at Intermembrane Junctions. AB - Short-range communication between cells is required for the survival of multicellular organisms. One mechanism of chemical signaling between adjacent cells employs surface displayed ligands and receptors that only bind when two cells make physical contact. Ligand-receptor complexes that form at the cell-cell junction and physically bridge two cells likely experience mechanical forces. A fundamental challenge in this area pertains to mapping the mechanical forces experienced by ligand-receptor complexes within such a fluid intermembrane junction. Herein, we describe the development of ratiometric tension probes for direct imaging of receptor tension, clustering, and lateral transport within a model cell-cell junction. These probes employ two fluorescent reporters that quantify both the ligand density and the ligand tension and thus generate a tension signal independent of clustering. As a proof-of-concept, we applied the ratiometric tension probes to map the forces experienced by the T-cell receptor (TCR) during activation and showed the first direct evidence that the TCR-ligand complex experiences sustained pN forces within a fluid membrane junction. We envision that the ratiometric tension probes will be broadly useful for investigating mechanotransduction in juxtacrine signaling pathways. PMID- 27192326 TI - Virulence and toxigenicity of coagulase-negative staphylococci in Nigerian traditional fermented foods. AB - The incidence of coagulase-negative staphylococci (CoNS) may render food unsafe, as the clinical isolates have been reported to exude virulent traits. A total of 255 CoNS isolates from 6 traditional fermented foods (nono, kunu, wara, iru, ogi, and kindirmo) from North Central Nigeria, identified as Staphylococcus epidermidis, Staphylococcus simulans, Staphylococcus xylosus, Staphylococcus kloosii, and Staphylococcus caprae, were investigated for virulence traits. The strains were examined for biofilm formation and production of hyaluronidase, DNase, TNase, haemolysins, and superantigenic toxins (SEA, SEB, SEC, SED, and TSST-1) using standard and genotypic methods. The analysis of virulence factors revealed the production of slime in 200 isolates (78.4%); alpha-haemolysin in 136 (53.3%); beta-haemolysin in 43 (16.9%); DNase in 199 (78.0%); TNase in 29 (11.4%); hyaluronidase in 125 (49.0%); TSST-1 in 119 (46.7%); and enterotoxin producing isolates SEA, SEB, SEC, and SED in 61 (23.9%), 19 (7.5%), 9 (3.5%), and 8 (3.1%), respectively. PCR analysis detected tsst-1, sea, seb, and sec genes. The ability of these microorganisms to exhibit virulence evokes the potential to cause disease especially under determinate conditions or in immune-compromised patients. The occurrence of CoNS in food should not be ignored nor their pathogenic potential considered as insignificant, rather safety measures should be taken to reduce or totally eliminate their occurrence in foods. PMID- 27192328 TI - Mercury in dental amalgam: Are our health care workers at risk? AB - : Dental amalgam in fillings exposes workers to mercury. The exposure to mercury was investigated among 1871 dental health care workers. The aim of the study was to evaluate the risk of mercury exposure among dental compared to nondental health care workers and to determine other risk factors for mercury exposure. Respondents answered questionnaires to obtain demographic, personal, professional, and workplace information and were examined for their own amalgam fillings. Chronic mercury exposure was assessed through urinary mercury levels. In total, 1409 dental and 462 nondental health care workers participated in the study. Median urine mercury levels for dental and nondental health care workers were 2.75 MUg/L (interquartile range [IQR] = 3.0175) and 2.66 MUg/L (IQR = 3.04) respectively. For mercury exposure, there were no significant risk factor found among the workers involved within the dental care. The Mann-Whitney test showed that urine mercury levels were significantly different between respondents who eat seafood more than 5 times per week compared to those who eat it less frequently or not at all (p = 0.003). The urinary mercury levels indicated significant difference between dental workers in their practice using squeeze cloths (Mann-Whitney test, p = 0.03). Multiple logistic regression showed that only the usage of cosmetic products that might contain mercury was found to be significantly associated with the urinary mercury levels (odds ratio [OR] = 15.237; CI: 3.612-64.276). Therefore, mean urinary mercury levels of health care workers were low. Exposure to dental amalgam is not associated with high mercury exposure. However, usage of cosmetic products containing mercury and high seafood consumption may lead to the increase of exposure to mercury. IMPLICATIONS: Exposure to the high levels of mercury from dental amalgam can lead to serious health effects among the dental health care workers. Nationwide chronic mercury exposure among dental personnel was assessed through urinary mercury levels. Findings suggest low urinary mercury levels of these health care workers. Exposure to dental amalgam is not associated with high mercury exposure. However, the usage of cosmetic products containing mercury and high seafood consumption may lead to the increase of exposure to mercury. PMID- 27192329 TI - Chromosome Mapping of 18S Ribosomal RNA Genes in Eleven Hypostomus Species (Siluriformes, Loricariidae): Diversity Analysis of the Sites. AB - We investigated the chromosomal distribution of 18S ribosomal DNA (rDNA) in different populations of 11 species of Hypostomus collected in important Brazilian basins, namely South Atlantic, Upper Parana, and Paraguay applying the fluorescence in situ hybridization (FISH). Hypostomus cochliodon, Hypostomus commersoni, Hypostomus hermanni, Hypostomus regani, Hypostomus albopunctatus, Hypostomus paulinus, Hypostomus aff. paulinus, Hypostomus iheringii, and Hypostomus mutucae presented multiple 18S rDNA sites while Hypostomus strigaticeps and Hypostomus nigromaculatus exhibited a single pair of chromosomes with 18S rDNA sites. The studied species presented variations in the number and position of these sites. The results accomplished were similar to those obtained by the analysis of AgNORs, revealing the same interspecific variability. Each species exhibited distinctive patterns of AgNOR and 18S rDNA distribution, which can be considered cytogenetic markers in each species of the genus and help improve the discussions on the phylogeny of the group. PMID- 27192333 TI - Doctor to Doctor. PMID- 27192331 TI - Students' knowledge of, and attitudes towards biotechnology revisited, 1995-2014: Changes in agriculture biotechnology but not in medical biotechnology. AB - Modern biotechnology is one of the most important scientific and technological revolutions in the 21st century, with an increasing and measurable impact on society. Development of biotechnology curriculum has become important to high school bioscience classrooms. This study has monitored high school students in Taiwan on their knowledge of and attitudes towards biotechnology for nearly two decades. Not surprisingly, knowledge of biotechnology of current students has increased significantly (p < 0.001) and most students have learned some definitions and examples of biotechnology. There was a positive correlation between biotechnology knowledge and attitudes toward biotechnology for current students who study Advanced Biology (AB). However, for current students who did not study AB, there was a negative correlation.The attitude results showed that students today expressed less favorable opinions toward agricultural biotechnology (p < 0.001) despite studying AB or not. However, there is no significant difference between students today and 18 years ago in opinions towards medical biotechnology. In addition, current students showed a greater concern involving environmental risks than former students. Interestingly, the high school curriculum did affect students' attitudes toward genetically engineered (GE) plants but not GE animals. Our current study also found that the students' attitude towards GE animals was influenced more by their limited knowledge than by their moral belief. On the basis of findings from this study, we suggest that more materials of emerging animal biotechnology should be included in high school curriculum and recommend that high school teachers and university faculty establish a collaborative framework in the near future. (c) 2016 by The International Union of Biochemistry and Molecular Biology, 44(5):475 491, 2016. PMID- 27192330 TI - Gender differences in treatment and clinical characteristics among patients receiving extended release naltrexone. AB - Further research is needed to investigate real-world acceptability of extended release naltrexone for alcohol and opioid use disorders, and potential gender differences. This study examines treatment and clinical characteristics among men and women receiving extended-release naltrexone in a large, publicly funded substance use disorder treatment system (N = 465; 52% female). Patient demographics, treatment characteristics, and the number of extended-release naltrexone doses received were collected from administrative data and treatment program staff. Additionally, patients provided information on experiences with extended-release naltrexone in an open-ended format at 1, 2, and 3 weeks following their first injection. For a subsample of patients (N = 220), alcohol/opioid cravings and specific adverse effects were also assessed. Compared to men, women reported experiencing a higher rate and mean number of adverse effects. Overall, craving scores showed substantial reductions over time. However, among patients taking extended-release naltrexone for alcohol use, women showed a significantly greater reduction in craving scores compared to men. No gender differences were observed in the number of extended-release naltrexone doses received. Although women may have a greater need for additional support in managing early adverse effects, extended-release naltrexone as an adjunct to psychosocial treatment may be an acceptable and promising treatment approach for both men and women, and particularly for women prescribed extended-release naltrexone for alcohol use. This study contributes further information on patients' experiences during the early course of extended-release naltrexone treatment in real-world settings. Understanding these experiences may assist policy makers and treatment providers in addressing challenges of implementing this treatment into wider practice. PMID- 27192335 TI - Readers' Forum. PMID- 27192334 TI - The Medical Bookshelf. PMID- 27192337 TI - Pearls. PMID- 27192336 TI - My Little Red Book. PMID- 27192338 TI - Interstate Postgraduate Medicine Association: Scottsdale Seminar. PMID- 27192339 TI - cme credit QUIZ. PMID- 27192340 TI - patient notes index. AB - Patient Notes are indexed alphabetically and by subject. The number immediately following the title is the number of the Patient Note, and the number in parentheses is the date of publication. This index includes all 82 Patient Notes published so far, from February 1, 1988, through this issue. PMID- 27192342 TI - Yo-yo dieting. PMID- 27192343 TI - Influence of Dosage and Type of Music Therapy in Symptom Management and Rehabilitation for Individuals with Schizophrenia. AB - The purpose of this systematic review was to investigate the influence of dosage, type (active, receptive, or combined), and format (individual or group) of music therapy for individuals with schizophrenia. With the terms "music*" and "schizophreni*," six research databases were searched: CINAHL, EMBASE, Music Index, PsycInfo, Pubmed, and RILM. The search was limited to studies written in English, peer-reviewed, and published between 1991 and 2015. Seventeen articles met the stated criteria. Dosage of music therapy ranged from 20 to 9,720 minutes. Three types of music therapy were delivered: active, receptive, or combined, and therapy was implemented via individual or group format. Depending on the dosage, type, and format, music therapy improved psychotic symptom management, depression and anxiety management, social and cognitive functioning, behavior, and quality of life of the participants. Dosage had a greater impact on the effects of music therapy compared to type and format. Studies that implemented a combination of active and receptive music therapy were more likely to produce significant improvements in outcomes compared to the studies that implemented the other types of music therapy. However, studies using combined type provided higher dosage of the intervention (e.g., more minutes of intervention exposure). This systematic review can be used to guide future research on and clinical applications for music therapy in this population. Future studies might also investigate the interaction of demographic characteristics or severity of illness with dosage and type on effects of music therapy. PMID- 27192346 TI - Contrasting photophysical properties of rhenium(i) tricarbonyl complexes having carbazole groups attached to the polypyridine ligand. AB - In the present work, new rhenium(i) polypyridyl compounds, fac [Re(L)(CO)3(cbz2phen)](+/0) where cbz2phen = 4,7-di(9H-carbazol-9-yl)-1,10 phenanthroline and L = Cl(-), pyridine (py) or 2-aminomethylpyridine (ampy) were synthesized and characterized by (1)H NMR, UV-Vis and IR spectroscopy combined with theoretical calculations using time-dependent density functional theory (TD DFT). Their photophysical properties were investigated by steady state and time resolved emission spectroscopy. These compounds show a strong and broad absorption band around 350-500 nm that, also by TD-DFT, corresponds to the carbazol -> phenanthroline intraligand charge transfer transition, (1)ILCTcbz2phen, with some contribution of the Re(i) -> phenanthroline metal-to ligand charge transfer transition, (1)MLCTRe->cbz2phen. In contrast to typical Re(i) polypyridyl complexes, cbz2phen-based Re(i) compounds exhibit two emission maxima in CH3CN solution and relatively low emission quantum yields, 10(-3)-10( 2). Solution phase time-resolved photoluminescence and excited state quenching experiments provided meaningful information on the presence of multiple emitter states after light excitation, which were identified as an (1)ILCTcbz2phen excited state deactivation at higher energies and a long-lived phosphorescence attributed to the (3)MLCTRe->cbz2phen excited state. When embedded into a PMMA matrix, the radiative decay from the singlet state is inhibited and the contribution of both (3)MLCT and (3)ILCTcbz2phen to the luminescence is observed. The photophysics of these Re(i) compounds reported herein provide new insights into the understanding of substitutional groups on the polypyridyl ligands that are relevant to practical and fundamental development of photo-induced molecular devices. PMID- 27192347 TI - Impact of a Risk Calculator on Risk Perception and Surgical Decision Making: A Randomized Trial. AB - OBJECTIVE: The aim of this study was to determine whether exposure to data from a risk calculator influences surgeons' assessments of risk and in turn, their decisions to operate. BACKGROUND: Little is known about how risk calculators inform clinical judgment and decision-making. METHODS: We asked a national sample of surgeons to assess the risks (probability of serious complications or death) and benefits (recovery) of operative and nonoperative management and to rate their likelihood of recommending an operation (5-point scale) for 4 detailed clinical vignettes wherein the best treatment strategy was uncertain. Surgeons were randomized to the clinical vignettes alone (control group; n = 384) or supplemented by data from a risk calculator (risk calculator group; n = 395). We compared surgeons' judgments and decisions between the groups. RESULTS: Surgeons exposed to the risk calculator judged levels of operative risk that more closely approximated the risk calculator value (RCV) compared with surgeons in the control group [mesenteric ischemia: 43.7% vs 64.6%, P < 0.001 (RCV = 25%); gastrointestinal bleed: 47.7% vs 53.4%, P < 0.001 (RCV = 38%); small bowel obstruction: 13.6% vs 17.5%, P < 0.001 (RCV = 14%); appendicitis: 13.4% vs 24.4%, P < 0.001 (RCV = 5%)]. Surgeons exposed to the risk calculator also varied less in their assessment of operative risk (standard deviations: mesenteric ischemia 20.2% vs 23.2%, P = 0.01; gastrointestinal bleed 17.4% vs 24.1%, P < 0.001; small bowel obstruction 10.6% vs 14.9%, P < 0.001; appendicitis 15.2% vs 21.8%, P < 0.001). However, averaged across the 4 vignettes, the 2 groups did not differ in their reported likelihood of recommending an operation (mean 3.7 vs 3.7, P = 0.76). CONCLUSIONS: Exposure to risk calculator data leads to less varied and more accurate judgments of operative risk among surgeons, and thus may help inform discussions of treatment options between surgeons and patients. Interestingly, it did not alter their reported likelihood of recommending an operation. PMID- 27192348 TI - Surgeon Perception of Risk and Benefit in the Decision to Operate. AB - OBJECTIVE: To determine how surgeons' perceptions of treatment risks and benefits influence their decisions to operate. BACKGROUND: Little is known about what makes one surgeon choose to operate on a patient and another chooses not to operate. METHODS: Using an online study, we presented a national sample of surgeons (N = 767) with four detailed clinical vignettes (mesenteric ischemia, gastrointestinal bleed, bowel obstruction, appendicitis) where the best treatment option was uncertain and asked them to: (1) judge the risks (probability of serious complications) and benefits (probability of recovery) for operative and nonoperative management and (2) decide whether or not they would recommend an operation. RESULTS: Across all clinical vignettes, surgeons varied markedly in both their assessments of the risks and benefits of operative and nonoperative management (narrowest range 4%-100% for all four predictions across vignettes) and in their decisions to operate (49%-85%). Surgeons were less likely to operate as their perceptions of operative risk increased [absolute difference (AD) = 29.6% from 1.0 standard deviation below to 1.0 standard deviation above mean (95% confidence interval, CI: -31.6, -23.8)] and their perceptions of nonoperative benefit increased [AD = -32.6% (95% CI: -32.8,--28.9)]. Surgeons were more likely to operate as their perceptions of operative benefit increased [AD = 18.7% (95% CI: 12.6, 21.5)] and their perceptions of nonoperative risk increased [AD = 32.7% (95% CI: 28.7, 34.0)]. Differences in risk/benefit perceptions explained 39% of the observed variation in decisions to operate across the four vignettes. CONCLUSIONS: Given the same clinical scenarios, surgeons' perceptions of treatment risks and benefits vary and are highly predictive of their decisions to operate. PMID- 27192349 TI - Dual-graft Adult Living Donor Liver Transplantation: An Innovative Surgical Procedure for Live Liver Donor Pool Expansion. AB - OBJECTIVE: To detail the surgical technique and outcomes of dual-graft (DG) adult living donor liver transplantation (ALDLT). BACKGROUND: DG ALDLT has a great potential for expanding the living donor pool without increasing donor risk. However, little is known about DG ALDLT because it has been performed by a limited number of institutions due to its technical complexity. METHODS: The clinical data of patients who underwent DG ALDLT at a single institute between March 2000 and December 2014 were retrospectively reviewed. RESULTS: In total, 400 DG ALDLTs, which accounted for 11.7% of all ALDLTs (n = 3387), were performed at our institute. The 1, 5, and 10-year patient survival rates of DG ALDLT were 89.2%, 85.5%, and 80.2%, respectively. In a propensity-matched cohort, there were no significant differences in the survival outcomes between DG and single-graft ALDLT (P = 0.163). Donor age, body mass index, and steatosis were significantly higher in the DG group. Additionally, the male predominance in the sex ratio of donors was lower in the DG group. In the DG group, the mean operative time was longer (18.7 vs 13.9 h; P < 0.001) and there was greater requirement for intraoperative transfusion of red blood cells (18.2 vs 11.4 units; P < 0.001). Additionally, the surgical complication rate per patient was significantly higher (53.7 vs 28.5%; P < 0.001). CONCLUSIONS: DG ALDLT enables us to achieve an acceptable survival outcome with 2 suboptimal grafts. However, technical complexity and longer operative time limit is its drawback. PMID- 27192350 TI - Investigating Adverse Event Free Admissions in Medicare Inpatients as a Patient Safety Indicator. AB - OBJECTIVE: To investigate adverse event free admissions as a potential, patient centered indicator aligned directly with the goal of patient safety-freedom from harm. BACKGROUND: Preventable adverse event rates in healthcare could be further reduced. These are generally measured separately, one adverse event at a time. However, this does not reveal whether different patients are affected or the same patients are experiencing multiple events. METHODS: We examined Medicare inpatient hospital administrative datasets for 2009 to 2011, processed using standard criteria. Events were (i) death within 30 days, (ii) unplanned readmissions within 30 days, (iii) long length of stay, (iv) healthcare acquired infections, and (v) established patient safety indicators not present on admission. We defined adverse event free admissions as those without record of any of these events. National rates were calculated by diagnosis group. Risk adjusted hospital-specific rates of adverse event free admissions were calculated using colorectal procedures as an example. RESULTS: There were 23,991,193 admissions after exclusions. Approximately, 64% went through the acute inpatient Medicare system without record of anything untoward. Multiple events were recorded in 22.7% admissions; 15% of these experienced more than 2 adverse events. Risk-adjusted hospital-specific rates of adverse event free admissions for colorectal procedures showed 131 out of 3786 hospitals below the 99.8% lower control limit of the national upper quartile. CONCLUSIONS: Overall, only 60% of admissions were recorded as adverse event free. Multiple adverse events were common. Even if events are under recorded, this measure could provide an easily understandable and useful baseline for clinicians and managers. PMID- 27192351 TI - An 18-Year Nationwide Cohort Study on The Association Between Diverticulitis and Colon Cancer. AB - OBJECTIVE: To investigate the association between diverticulitis and colon cancer in a large, nationwide cohort study. BACKGROUND: Diverticulitis is a common disease, especially in the Western world. Previous articles have investigated the association between diverticulitis and colon cancer with inconclusive results. METHODS: We conducted a population-based cohort study based on longitudinal Danish national registers with data from the period 1995 to 2012. Data were extracted from comprehensive Danish national registers containing information from both public and private hospitals. Patients with diverticulitis were identified from the registers and matched by sex and age (+/- 1 year) with a ratio of 1:10 to people who did not have a registration of diverticulitis or diverticulosis. Main outcome was the event of colon cancer. Subgroup analyses were performed to investigate the effect of colonoscopies and treatment on the colon cancer rate after diverticulitis. RESULTS: A total of 445,456 people were included, of whom 40,496 had a diagnosis of diverticulitis. The incidence of colon cancer in the group with diverticulitis (4.3%) and the group without diverticulitis (2.3%) differed significantly (P < 0.001) with an incidence rate ratio of 1.86 (95% confidence interval, CI, 1.77-1.96). When adjusted for possible confounders, the association between diverticulitis and cancer remained significant with an odds ratio (OR) of 2.20 (95% CI 2.08-2.32) (P < 0.001). Those with diverticulitis, who had no colonoscopy, had an increased risk of colon cancer compared with those without both diverticulitis and colonoscopy with an OR of 2.72 (95% CI 2.64-2.94) (P < 0.001). CONCLUSIONS: We found a strong association between development of diverticulitis and colon cancer. This raises several questions regarding the possible causal association and warrants further studies. Patients with diverticulitis should undergo endoscopic surveillance for colon cancer. PMID- 27192353 TI - Secondary Structures of Ubiquitin Ions Soft-Landed onto Self-Assembled Monolayer Surfaces. AB - The secondary structures of multiply charged ubiquitin ions soft-landed onto self assembled monolayer (SAM) surfaces were studied using in situ infrared reflection absorption spectroscopy (IRRAS). Two charge states of ubiquitin, 5+ and 13+, were mass selected separately from a mixture of different charge states produced by electrospray ionization (ESI). The low 5+ charge state represents a nativelike folded state of ubiquitin, while the high 13+ charge state assumes an extended, almost linear conformation. Each of the two charge states was soft-landed onto a CH3- and COOH-terminated SAM of alkanethiols on gold (HSAM and COOH-SAM). HSAM is a hydrophobic surface known to stabilize helical conformations of soft-landed protonated peptides, whereas COOH-SAM is a hydrophilic surface that preferentially stabilizes beta-sheet conformations. IRRAS spectra of the soft landed ubiquitin ions were acquired as a function of time during and after ion soft-landing. Similar to smaller peptide ions, helical conformations of ubiquitin are found to be more abundant on HSAM, while the relative abundance of beta-sheet conformations increases on COOH-SAM. The initial charge state of ubiquitin also has a pronounced effect on its conformation on the surface. Specifically, on both surfaces, a higher relative abundance of helical conformations and a lower relative abundance of beta-sheet conformations are observed for the 13+ charge state compared to the 5+ charge state. Time-resolved experiments indicate that the alpha-helical band in the spectrum of the 13+ charge state slowly increases with time on the HSAM surface and decreases in the spectrum of the 13+ charge state on COOH-SAM. These results further support the preference of the hydrophobic HSAM surface toward helical conformations and demonstrate that soft landed protein ions may undergo slow conformational changes during and after deposition. PMID- 27192352 TI - Economic Impact of Routine Cavity Margins Versus Standard Partial Mastectomy in Breast Cancer Patients: Results of a Randomized Controlled Trial. AB - OBJECTIVE: The aim of the study was to compare costs associated with excision of routine cavity shave margins (CSM) versus standard partial mastectomy (PM) in patients with breast cancer. BACKGROUND: Excision of CSM reduces re-excision rates by more than 50%. The economic implications of this is, however, unclear. METHODS: Between October 21, 2011 and November 25, 2013, 235 women undergoing PM for Stage 0-III breast cancer were randomized to undergo either standard PM ("no shave", n = 116) or have additional CSM taken ("shave", n = 119). Costs from both a payer and a hospital perspective were measured for index surgery and breast cancer surgery-related care through subsequent 90 days. RESULTS: The 2 groups were well-matched in terms of baseline characteristics. Those in the "shave" group had a longer operative time at the initial surgery (median 76 vs 66 min, P < 0.01), but a lower re-excision rate for positive margins (13/119 = 10.9% vs 32/116 = 27.6%, P < 0.01). Actual direct hospital costs associated with operating room time ($1315 vs. $1137, P = 0.03) and pathology costs ($1195 vs $795, P < 0.01) were greater for the initial surgery in patients in the "shave" group. Taking into account the index surgery and the subsequent 90 days, there was no significant difference in cost from either the payer ($10,476 vs $11,219, P = 0.40) or hospital perspective ($5090 vs $5116, P = 0.37) between the "shave" and "no shave" groups. CONCLUSIONS: Overall costs were not significantly different between the "shave" and "no shave" groups due to significantly fewer reoperative surgeries in the former. PMID- 27192354 TI - Electro-dewatering of activated sludge: Electrical resistance analysis. AB - The significant risk of ohmic heating and the high electric energy consumption at terminal stages of the dewatering are two problems that hamper the development of the electro-dewatering (EDW) technology. In the future prospect of studying these two issues, it is important to provide and analyse quantitative data relative to the behavior of the electric resistance in EDW. It was the main goal of this study. It showed that the electric resistance of the complete system (cake + filter cloth) depended on the cake dryness. It increased sharply when the solids content exceeded around 45%.The solids loading also influenced the apparent resistance at the beginning of the process. The electric resistance of the filter cloth represented about 20% of the total resistance. It remained relatively constant over the process except at the terminal stage where it generally increased sharply. The use of conductive filter, such as metallic cloth, enabled to decrease the electric resistance and reduce the energy consumption of the process. The electric resistance decreased across the cake from the anode to the cathode. This behavior may be explained by several phenomena such as the ions migration and their interaction with the solid, the decrease of dry solids content from the anode to the cathode and the gas presence at the anode (due to electrolysis reaction). PMID- 27192355 TI - Toward a better understanding of coagulation for dissolved organic nitrogen using polymeric zinc-iron-phosphate coagulant. AB - The increase of agricultural related activities and the lack of effective waste control has led to an increase of organic nitrogen in water. The development of coagulants to effectively remove dissolved organic nitrogen (DON) is a high priority in the water treatment industry. We developed a polymeric zinc-iron phosphate (ZnFeP) coagulant and investigated its coagulation effect on DON removal. Optimum coagulant for coagulation for DON and TDN removals was characterized by the dense convex-concave packing structure differing from other zinc-based coagulant, polycrystalline structure and high content colloidal species, which could account up to 87% of the total colloidal species. Coagulation experiments showed the DON removal rate to vary greatly depending on principal components and their interaction with metals, phosphate and hydroxyl. DON removal efficiency increased with the increase of colloidal species. The coagulation was also dependent on coagulant dosage and water quality parameters: Coagulation efficiency increased with coagulant dosage in the investigated range of 1-16 mg/l, and a pH of 6 was found to be superior for the coagulation. DON removal efficiency was also higher than and linearly correlated with total dissolved nitrogen (TDN) removal, which implies that an effective coagulation for TDN is also effective for DON. The findings in this study indicate that coagulation of DON is largely influenced by coagulant composition and species. We also found the removal of DON by our newly developed polymeric ZnFeP coagulant to be effective. PMID- 27192356 TI - Inflow rate-driven changes in the composition and dynamics of chromophoric dissolved organic matter in a large drinking water lake. AB - Drinking water lakes are threatened globally and therefore in need of protection. To date, few studies have been carried out to investigate how the composition and dynamics of chromophoric dissolved organic matter (CDOM) in drinking water lakes are influenced by inflow rate. Such CDOM can lead to unpleasant taste and odor of the water and produce undesirable disinfection byproducts during drinking water treatment. We studied the drinking water Lake Qiandao, China, and found that the concentrations of suspended particulate matter (SPM) in the lake increased significantly with inflow rate (p < 0.001). Similarly, close relationships between inflow rate and the CDOM absorption coefficient at 350 nm a(350) and with terrestrial humic-like fluorescence C3 and a negative relationship between inflow rate and the first principal component (PC1) scores, which, in turn, were negatively related to the concentrations and relative molecular size of CDOM (p < 0.001), i.e. the concentration and molecular size of CDOM entering the lake increased proportionately with inflow rate. Furthermore, stable isotopes (deltaD and delta(18)O) were depleted in the upstream river mouth relative to downstream remaining lake regions, substantiating that riverine CDOM entering the lake was probably driven by inflow rate. This was further underpinned by remarkably higher mean chlorophyll-a and in situ measured terrestrial CDOM fluorescence (365/480 nm) and apparent oxygen utilization (AOU), and notably lower mean PC1 and CDOM spectral slope (S275-295) recorded in the upstream river mouth than in the downstream main lake area. Strong negative correlations between inflow rate and a(250):a(365), S275-295, and the spectral slope ratio (SR) implied that CDOM input to the lake in rainy period was dominated by larger organic molecules with a more humic-like character. Rainy period, especially rainstorm events, therefore poses a risk to drinking water safety and requires higher removal efficiency of CDOM during drinking water treatment processes. PMID- 27192357 TI - Molecular diversity of riverine alkaline-extractable sediment organic matter and its linkages with spectral indicators and molecular size distributions. AB - Few studies have been conducted to examine the spatial heterogeneity of riverine sediment organic matter (SOM) at the molecular level. The present study explored the chemical and molecular heterogeneity of alkaline-extractable SOM from riverine sediments via multiple analytical tools including molecular composition, absorption and fluorescence spectra, and molecular size distributions. The riverine SOM revealed complex and diverse characteristics, exhibiting a great number of non-redundant formulas and high spatial variations. The molecular diversity was more pronounced for the sediments affected by a higher degree of anthropogenic activities. Unlike the cases of aquatic dissolved organic matter, highly-unsaturated structures with oxygen (HUSO) of SOM were more associated with the spectral and size features of humic-like (or terrestrial) substances than aromatic molecules were, cautioning the interpretation of the SOM molecules responsible for apparent indicators. Noting that a higher detection rate (DR) produces fewer common molecules, the common molecules of 23 different SOMs were determined at a reasonable DR value of 0.35, which accounted for a small portion (5.8%) of all detected molecules. They were mainly CHO compounds (>98%), which positively correlated with spectral indicators of biological production. Despite the low abundance, however, the ratios of aromatic to aliphatic substances could be indexed to classify the common molecules into several geochemical molecular groups with different degrees of the associations with the apparent spectral and size indicators. PMID- 27192358 TI - Human fecal and pathogen exposure pathways in rural Indian villages and the effect of increased latrine coverage. AB - Efforts to eradicate open defecation and improve sanitation access are unlikely to achieve health benefits unless interventions reduce microbial exposures. This study assessed human fecal contamination and pathogen exposures in rural India, and the effect of increased sanitation coverage on contamination and exposure rates. In a cross-sectional study of 60 villages of a cluster-randomized controlled sanitation trial in Odisha, India, human and domestic animal fecal contamination was measured in community tubewells and ponds (n = 301) and via exposure pathways in homes (n = 354), using Bacteroidales microbial source tracking fecal markers validated in India. Community water sources were further tested for diarrheal pathogens (rotavirus, adenovirus and Vibrio cholerae by quantitative PCR; pathogenic Escherichia coli by multiplex PCR; Cryptosporidium and Giardia by immunomagnetic separation and direct fluorescent antibody microscopy). Exposure pathways in intervention and control villages were compared and relationships with child diarrhea examined. Human fecal markers were rarely detected in tubewells (2.4%, 95%CI: 0.3-4.5%) and ponds (5.6%, 95%CI: 0.8-10.3%), compared to homes (35.4%, 95%CI: 30.4-40.4%). In tubewells, V. cholerae was the most frequently detected pathogen (19.8%, 95%CI: 14.4-25.2%), followed by Giardia (14.8%, 95%CI: 10.0-19.7%). In ponds, Giardia was most often detected (74.5%, 95%CI: 65.7-83.3%), followed by pathogenic E. coli (48.1%, 95%CI: 34.8-61.5%) and rotavirus (44.4%, 95%CI: 34.2-54.7%). At village-level, prevalence of fecal pathogen detection in community drinking water sources was associated with elevated prevalence of child diarrhea within 6 weeks of testing (RR 2.13, 95%CI: 1.25-3.63) while within homes, higher levels of human and animal fecal marker detection were associated with increased risks of subsequent child diarrhea (P = 0.044 and 0.013, respectively). There was no evidence that the intervention, which increased functional latrine coverage and use by 27 percentage points, reduced human fecal contamination in any tested pathway, nor the prevalence of pathogens in water sources. In conclusion, the study demonstrates that (1) improved sanitation alone may be insufficient and further interventions needed in the domestic domain to reduce widespread human and animal fecal contamination observed in homes, (2) pathogens detected in tubewells indicate these sources are microbiologically unsafe for drinking and were associated with child diarrhea, (3) domestic use of ponds heavily contaminated with multiple pathogens presents an under-recognized health risk, and (4) a 27 percentage point increase in improved sanitation access at village-level did not reduce detectable human fecal and pathogen contamination in this setting. PMID- 27192359 TI - The Effects of Tonsillectomy Education Using Smartphone Text Message for Mothers and Children Undergoing Tonsillectomy: A Randomized Controlled Trial. AB - BACKGROUND: Tonsillectomy is the most common type of surgical procedure performed in preschool children. Due to short period of hospitalization, mothers are expected to manage their children's care at home. However, they are rarely provided with sufficient information about postoperative management. This study aims to determine the effectiveness of providing caregivers with information on tonsillectomy care by smartphone text messaging in increasing their mothers' knowledge, reducing the anxiety, and improving the sick-role behavior of pediatric tonsillectomy patients. MATERIALS AND METHODS: A sample of 61 pediatric patients and their mothers was recruited. Participants were randomly assigned into either the experimental group (n = 27) or the control group (n = 34). The control group was given information about the tonsillectomy by conventional textual and verbal means, whereas the experimental group received the same information in the form of 10 text messages during the period from hospitalization to their first follow-up visits. RESULTS: Results of mixed design, two-way analysis of variance indicated significant interaction effects between time points and groups for mothers' knowledge (F = 4.26, p = 0.043) and children's anxiety (F = 3.32; p = 0.037). Thus, the results do support the effectiveness of tonsillectomy education using smartphone text messaging in increasing mothers' knowledge and reducing children's anxiety. CONCLUSIONS: These results can be applied to preoperative and postoperative interventions for children not only for tonsillectomy but also for many other operations. The development of various educational programs using smartphone text messaging for postoperative patient management would also be valuable. PMID- 27192361 TI - Basophilic differentiation in transient abnormal myelopoiesis. PMID- 27192363 TI - Editorial. PMID- 27192362 TI - Ultrahigh-Performance Liquid Chromatography-High-Resolution Quadrupole Time-of Flight Mass Spectrometry Based Metabolomics Reveals Key Differences between Brachiaria decumbens and B. brizantha, Two Similar Pastures with Different Toxicities. AB - Several species of Brachiaria (Poaceae) currently cover extensive grazing areas in Brazil, providing valuable source of feed for a large cattle population. However, numerous cases of toxicity outbreaks in livestock have raised concerns on safety of using these plants, especially B. decumbens. In this study, chemometric analysis of ultrahigh-performance liquid chromatography-high resolution quadrupole time-of-flight mass spectrometry (UHPLC-HR-QTOF-MS) data has for the first time uncovered qualitative and quantitative differences between metabolomes of toxic B. decumbens and nontoxic B. brizantha. The steroidal saponin protoneodioscin was established as the main biomarker for B. decumbens when compared to B. brizantha, and therefore the key explanation for their phytochemical differentiation. Quantification of protodioscin in both plants showed no significant differences; consequently, the idea that this compound is solely responsible for toxicity outbreaks must be discarded. Instead, we propose that the added occurrence of its stereoisomer, protoneodioscin, in B. decumbens, can be considered as the probable cause of these events. Interestingly, the greatest concentrations of saponins for both species were reached during winter (B. decumbens = 53.6 +/- 5.1 mg.g(-1) dry weight (D.W.); B. brizantha = 25.0 +/- 1.9 mg.g(-1) D.W.) and spring (B. decumbens = 49.4 +/- 5.0 mg.g(-1) D.W.; B. brizantha = 27.9 +/- 1.4 mg.g(-1) D.W.), although in the case of B. decumbens these values do not vary significantly among seasons. PMID- 27192365 TI - Myers-Briggs typology and Jungian individuation. AB - Myers-Briggs typology is widely seen as equivalent to and representative of Jungian theory by the users of the Myers-Briggs Type Indicator (MBTI) and similar questionnaires. However, the omission of the transcendent function from the theory, and the use of typological functions as its foundation, has resulted in an inadvertent reframing of the process of individuation. This is despite some attempts to integrate individuation and typology, and reintroduce the transcendent function into Myers-Briggs theory. This paper examines the differing views of individuation in Myers-Briggs and Jungian theory, and some of the challenges of reconciling those differences, particularly in the context of normality. It proposes eight principles, drawn mainly from Jungian and classical post-Jungian work, that show how individuation as a process can be integrated with contemporary Myers-Briggs typology. These principles show individuation as being a natural process that can be encouraged outside of the analytic process. They make use of a wide range of opposites as well as typological functions, whilst being centred on the transcendent function. Central to the process is the alchemical image of the caduceus and a practical interpretation of the axiom of Maria, both of which Jung used to illustrate the process of individuation. PMID- 27192364 TI - Boundary and analytic attitude: reflections on a summer holiday break. AB - The effect of a boundary in analytic work at the summer holiday break is discussed in relation to archetypal experiences of exclusion, loss and limitation. Some attempts by patients to mitigate an analyst's act of separation are reviewed as enactments, and in particular the meanings of a gift made by one patient. Analytic attitude towards enactment from within different schools of practice is sketched, with reference to the effect on the analyst of departing from the received practice of their own allegiance. A theory is adumbrated that the discomfort of 'contravening the rules' has a useful effect in sparking the analyst into consciousness, with greater attention to salient features in an individual case. Interpretation as an enactment is briefly considered, along with the possible effects of containing the discomfort of a patient's enactment in contrast to confronting it with interpretation. PMID- 27192360 TI - Prospective Study of Acute HIV-1 Infection in Adults in East Africa and Thailand. AB - BACKGROUND: Acute human immunodeficiency virus type 1 (HIV-1) infection is a major contributor to transmission of HIV-1. An understanding of acute HIV-1 infection may be important in the development of treatment strategies to eradicate HIV-1 or achieve a functional cure. METHODS: We performed twice-weekly qualitative plasma HIV-1 RNA nucleic acid testing in 2276 volunteers who were at high risk for HIV-1 infection. For participants in whom acute HIV-1 infection was detected, clinical observations, quantitative measurements of plasma HIV-1 RNA levels (to assess viremia) and HIV antibodies, and results of immunophenotyping of lymphocytes were obtained twice weekly. RESULTS: Fifty of 112 volunteers with acute HIV-1 infection had two or more blood samples collected before HIV-1 antibodies were detected. The median peak viremia (6.7 log10 copies per milliliter) occurred 13 days after the first sample showed reactivity on nucleic acid testing. Reactivity on an enzyme immunoassay occurred at a median of 14 days. The nadir of viremia (4.3 log10 copies per milliliter) occurred at a median of 31 days and was nearly equivalent to the viral-load set point, the steady state viremia that persists durably after resolution of acute viremia (median plasma HIV-1 RNA level, 4.4 log10 copies per milliliter). The peak viremia and downslope were correlated with the viral-load set point. Clinical manifestations of acute HIV-1 infection were most common just before and at the time of peak viremia. A median of one symptom of acute HIV-1 infection was recorded at a median of two study visits, and a median of one sign of acute HIV-1 infection was recorded at a median of three visits. CONCLUSIONS: The viral-load set point occurred at a median of 31 days after the first detection of plasma viremia and correlated with peak viremia. Few symptoms and signs were observed during acute HIV-1 infection, and they were most common before peak viremia. (Funded by the Department of Defense and the National Institute of Allergy and Infectious Diseases.). PMID- 27192366 TI - The use of Skype in analysis and training: a research and literature review. AB - Of recent years there has not only been an increasing use of Skype in analytic treatment, supervision and teaching, but also a number of writers have been endeavouring to assess its effectiveness. Whilst it is generally agreed that Skype can facilitate an analytic encounter where distance prohibits a face-to face process, where continuity needs to be maintained and where analysands are in areas far from specialized centres, there is divergence in the literature as to whether analysis, as opposed to psychotherapy, can be successful using Skype. This paper reviews the literature and concludes that the essentials of a genuine analytic process are not necessarily precluded by Skype. One central reason is because there exists a cross-modal communication channel between the human senses (underpinned by audiovisual mirror neurons) in addition to the recently discovered instinct for communication and interpersonal understanding, and these can override the need for physical proximity of the participants. The essentials of an analytic frame can thus be maintained, and the continuity that Skype enables means that containment is also facilitated and this counters the negative aspects of shuttle analysis. The critical issues for the profession then become the professional development for practitioners in the use of Skype and suggestions are listed. PMID- 27192367 TI - Jung, Winnicott and the divided psyche. AB - In his review of Memories Dreams Reflections, Winnicott diagnosed Jung as suffering from a psychic split, and characterized the content and the structure of analytical psychology as primarily moulded and conditioned by Jung's own defensive quest for a 'self that he could call his own'. This pathologizing analysis continues to be endorsed by contemporary Jungian writers. In this paper I attempt to show that Winnicott's critique is fundamentally misguided because it derives from a psychoanalytic model of the psyche, a model that regards all dissociation as necessarily pathological. I argue that Jung's understanding of the psyche differs radically from this model, and further, that it conforms by and large to the kind of dissociative model that we find in the writings of Frederic Myers, William James and Theodor Flournoy. I conclude that a fruitful relationship between psychoanalysis and analytical psychology must depend upon an awareness of these important differences between the two psychic models. PMID- 27192368 TI - Winnicott redux: a reply to Saban. PMID- 27192369 TI - A response to William Meredith-Owen. PMID- 27192370 TI - Jung in education: a review of historical and contemporary contributions from analytical psychology to the field of education. AB - The available literature on the influence of Jungian thought on the theory and practice of education leaves the impression that although the work of Carl Jung and analytical psychology have much to offer the field of education, the Jungian influence has so far been slight. While this has certainly been true, the last decade or so has nevertheless witnessed an increased scholarly interest in exploring how analytical psychology may inform and inspire the field of education. As an explanation for this burgeoning interest in Jung, several of the contemporary contributors mention that analytical psychology has the potential of functioning as a counterbalance to the tendencies in Western societies to focus on measurable learning targets and increasingly standardized measures of teaching and assessment. It seems pertinent then to gain an overview of how analytical psychology has so far inspired the field of education and how it may fruitfully continue do so in the future. To this end this paper is structured chronologically, starting with the different phases of Jung's own engagement with the field of education and ending with later post-Jungian applications of his concepts and ideas to education. PMID- 27192371 TI - William Willeford (1929-2015). PMID- 27192375 TI - The 2015 Most Influential Bioelectromagnetics Journal Paper by Citation Award. PMID- 27192374 TI - Advancing our understanding of infant bronchiolitis through phenotyping and endotyping: clinical and molecular approaches. AB - INTRODUCTION: Bronchiolitis is a major public health problem worldwide. However, no effective treatment strategies are available, other than supportive care. AREAS COVERED: Although bronchiolitis has been considered a single disease diagnosed based on clinical characteristics, emerging evidence supports both clinical and pathobiological heterogeneity. The characterization of this heterogeneity supports the concept that bronchiolitis consists of multiple phenotypes or consistent grouping of characteristics. Expert commentary: Using unbiased statistical approaches, multidimentional clinical characteristics will derive bronchiolitis phenotypes. Furthermore, molecular and systems biology approaches will, by linking pathobiology to phenotype, identify endotypes. Large cohort studies of bronchiolitis with comprehensive clinical characterization and system-wide profiling of the '-omics' data (e.g., host genome, transcriptome, epigenome, viral genome, microbiome, metabolome) should enhance our ability to molecularly understand these phenotypes and lead to more targeted and personalized approaches to bronchiolitis treatment. PMID- 27192376 TI - Opinion Leaders in Online Cancer Support Groups: An Investigation of Their Antecedents and Consequences. AB - With a focus on the nature and dynamic process of social interactions among breast cancer patients, this study argues that the notion of opinion leaders can be another crucial factor in explaining positive psychosocial health outcomes within computer-mediated social support (CMSS) groups. This study investigates the relationship between opinion leaders and their psychosocial health benefits by considering two overarching questions: (a) Who are the opinion leaders? (b) What role do these opinion leaders play in explaining health outcomes? The data analyzed in this study resulted from merging human-coded content analysis of discussion group messages, action log data analysis of interactive health system usage, and longitudinal survey data. Surveys were administered to 221 women with breast cancer; participants were provided free access to and training for the CMSS groups developed by the Comprehensive Health Support System (CHESS) project. The findings suggest that opinion leaders obtained psychosocial health benefits, such as higher levels of cancer information competence, breast cancer knowledge, and better problem-focused coping strategies. Those who had a higher baseline level of breast cancer knowledge and optimism in coping with challenges in their life were more likely to act as opinion leaders. Implications for research and improving psychosocial interventions for people with health concerns are discussed. PMID- 27192377 TI - Effects of Well-Controlled HIV Infection on Complement Activation and Function. AB - INTRODUCTION: Uncontrolled HIV infection is known to activate the complement system, leading to an increase in chronic inflammation. Whether or not this activation of complement persists and contributes to chronic inflammation in subjects with HIV infection that is well controlled through use of antiretroviral therapy has not been studied. METHODS: We conducted an observational, cross sectional study using sera from 305 adults with well-controlled HIV infection and 30 healthy controls. Sera was tested for markers of complement activation (C3a and C5a levels), complement function (CH50 assay), and immunoglobulin levels (IgG1-IgG4) as IgG can activate complement. We evaluated the association of well controlled HIV infection with C3a, C5a, CH50, IgG1-IgG4, and total IgG levels using both univariate and multivariate analyses, controlling for factors such as age, sex, race, comorbidities (including hepatitis C coinfection), smoking status, and statin use. RESULTS: Well-controlled HIV infection was associated with a 54% increase in complement activation as measured by C3a levels compared with healthy controls (P < 0.0001). Hepatitis C coinfection was associated with a further 52% increase in complement activation, as measured by C3a levels, over HIV alone (P = 0.003). CONCLUSION: These results suggest that complement activation may contribute to a proinflammatory state even in well-controlled HIV infection. Furthermore, hepatitis C virus coinfection may be even more proinflammatory, in complement activation, compared with HIV infection alone. PMID- 27192378 TI - Grafted Vitamin-E UHMWPE may increase the durability of posterior stabilized and constrained condylar total knee replacements. AB - The suitability of grafted vitamin-E highly crosslinked polyethylene (VE-HXPE) for use in posterior stabilized (PS) and constrained condylar knee (CCK) applications has not been explored. We hypothesized that VE-HXPE performs better than conventional and crosslinked polyethylene under clinically relevant conditions. PS tibial post fracture resistance under adverse shear loading conditions, CCK tibial post resistance to torsional fatigue, delamination resistance under high stress, and wear resistance were evaluated. Grafted VE-HXPE exhibits (1) 10% and 57% improved PS post fatigue strength compared to conventional PE (CPE) and remelted HXPE; (2) 45% improved CCK post fatigue strength compared to CPE; (3) Greater than 36* the delamination resistance of CPE; and (4) 96% and 73% wear reduction compared to CPE and HXPE. VE-HXPE performed well under clinically relevant in vitro conditions. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1789-1798, 2017. PMID- 27192380 TI - Selected Summaries. PMID- 27192382 TI - Erratum. PMID- 27192379 TI - Quantifying the impact of underlying measurement error on cervical spinal cord diffusion tensor imaging at 3T. AB - PURPOSE: To empirically characterize and quantify the impact of gradient weighting schemes on the appearance and fidelity of diffusion tensor imaging of the human spinal cord in vivo in clinically relevant scan time equivalents (STE). MATERIALS AND METHODS: In five healthy controls at 3T, we evaluated test-retest reproducibility and performed voxelwise analysis of diffusion tensor imaging (DTI)-derived indices (fractional anisotropy [FA], mean [MD], axial [AD], and radial [RD] diffusivity) in the cervical spinal cord to assess spatial dependencies of measurement error and differences across three different sampling schemes (6, 15, and 32 directions) at STE of 4.5, 9, and 18 minutes. A subjective assessment was also performed. RESULTS: With six directions, column-specific errors are highest (effect size = 2.9%, 4.4%, 7.2% for FA in dorsal column, lateral column, and gray matter) and different than the 15-direction scheme (P < 0.05). STE sequences with 15 and 32 directions exhibited small differences in error (P > 0.05). For FA and AD, measurement errors are prevalent in gray matter, while partial volume effects with cerebrospinal fluid heavily influence RD. Measurement errors decreased with increasing scan time (P < 0.01), albeit with diminishing returns at scan times longer than 9 minutes (P < 0.05). CONCLUSION: A 15-direction scheme of 9 minutes yields measurements of the cervical spinal cord with low error. J. Magn. Reson. Imaging 2016;44:1608-1618. PMID- 27192383 TI - Transcatheter Aortic Valve Implantation and Morbidity and Mortality-Related Factors: a 5-Year Experience in Brazil. AB - BACKGROUND: Transcatheter aortic valve implantation has become an option for high surgical-risk patients with aortic valve disease. OBJECTIVE: To evaluate the in hospital and one-year follow-up outcomes of transcatheter aortic valve implantation. METHODS: Prospective cohort study of transcatheter aortic valve implantation cases from July 2009 to February 2015. Analysis of clinical and procedural variables, correlating them with in-hospital and one-year mortality. RESULTS: A total of 136 patients with a mean age of 83 years (80-87) underwent heart valve implantation; of these, 49% were women, 131 (96.3%) had aortic stenosis, one (0.7%) had aortic regurgitation and four (2.9%) had prosthetic valve dysfunction. NYHA functional class was III or IV in 129 cases (94.8%). The baseline orifice area was 0.67 +/- 0.17 cm2 and the mean left ventricular-aortic pressure gradient was 47.3+/-18.2 mmHg, with an STS score of 9.3% (4.8%-22.3%). The prostheses implanted were self-expanding in 97% of cases. Perioperative mortality was 1.5%; 30-day mortality, 5.9%; in-hospital mortality, 8.1%; and one year mortality, 15.5%. Blood transfusion (relative risk of 54; p = 0.0003) and pulmonary arterial hypertension (relative risk of 5.3; p = 0.036) were predictive of in-hospital mortality. Peak C-reactive protein (relative risk of 1.8; p = 0.013) and blood transfusion (relative risk of 8.3; p = 0.0009) were predictive of 1-year mortality. At 30 days, 97% of patients were in NYHA functional class I/II; at one year, this figure reached 96%. CONCLUSION: Transcatheter aortic valve implantation was performed with a high success rate and low mortality. Blood transfusion was associated with higher in-hospital and one-year mortality. Peak C-reactive protein was associated with one-year mortality. PMID- 27192384 TI - Mortality from Circulatory System Diseases and Malformations in Children in the State of Rio de Janeiro. AB - BACKGROUND: The epidemiological profile of mortality in a population is important for the institution of measures to improve health care and reduce mortality Objective: To estimate mortality rates and the proportional mortality from cardiovascular diseases and malformations of the circulatory system in children and adolescents. METHODS: This is a descriptive study of mortality from cardiovascular diseases, malformations of the circulatory system, from all causes, ill-defined causes and external causes in children and adolescents in the state of Rio de Janeiro from 1996 to 2012. Populations were obtained from the Brazilian Institute of Geography and Statistics (Instituto Brasileiro de Geografia e Estatistica - IBGE) and deaths obtained from the Department of Informatics of the Unified Health System (DATASUS)/Ministry of Health. RESULTS: There were 115,728 deaths from all causes, 69,757 in males. The annual mortality from cardiovascular diseases was 2.7/100,000 in men and 2.6/100,000 in women. The annual mortality from malformations of the circulatory system was 7.5/100,000 in men and 6.6/100,000 in women. Among the specific causes of circulatory diseases, cardiomyopathies had the highest rates of annual proportional mortality, and from malformations of the circulatory system, it occurred due to unspecified malformations of the circulatory system, at all ages and in both genders. CONCLUSION: Mortality from malformations of the circulatory system was most striking in the first years of life, while cardiovascular diseases were more relevant in adolescents. Low access to prenatal diagnosis or at birth probably prevented the proper treatment of malformations of the circulatory system. PMID- 27192385 TI - Association between Spirituality and Adherence to Management in Outpatients with Heart Failure. AB - BACKGROUND: Spirituality may influence how patients cope with their illness. OBJECTIVES: We assessed whether spirituality may influence adherence to management of outpatients with heart failure. METHODS: Cross sectional study enrolling consecutive ambulatory heart failure patients in whom adherence to multidisciplinary treatment was evaluated. Patients were assessed for quality of life, depression, religiosity and spirituality utilizing validated questionnaires. Correlations between adherence and psychosocial variables of interest were obtained. Logistic regression models explored independent predictors of adherence. RESULTS: One hundred and thirty patients (age 60 +/- 13 years; 67% male) were interviewed. Adequate adherence score was observed in 38.5% of the patients. Neither depression nor religiosity was correlated to adherence, when assessed separately. Interestingly, spirituality, when assessed by both total score sum (r = 0.26; p = 0.003) and by all specific domains, was positively correlated to adherence. Finally, the combination of spirituality, religiosity and personal beliefs was an independent predictor of adherence when adjusted for demographics, clinical characteristics and psychosocial instruments. CONCLUSION: Spirituality, religiosity and personal beliefs were the only variables consistently associated with compliance to medication in a cohort of outpatients with heart failure. Our data suggest that adequately addressing these aspects on patient's care may lead to an improvement in adherence patterns in the complex heart failure management. PMID- 27192386 TI - Comparison of pollutant concentrations from weekly discrete versus composite samples for residential dry-weather runoff. AB - As urbanization has increased, so has degradation of urban streams. Urban water quality monitoring has focused on storm runoff sampling, but in arid climates, dry-weather runoff is a significant contributor of pollutants to aquatic systems. The majority of dry-weather runoff studies sample a small window of the entire dry-season. For this study constituent concentrations were compared using two sampling protocols. The first protocol repeatedly collected samples on the same day of the week at the same time of day. The second protocol collected samples during two week-long intensive sampling events consisting of sample collection every hour for 24 h for seven consecutive days. The two protocols were compared to determine if sampling at the same time of the week was representative of the entire week. For nitrate, total phosphorous, fipronil, permethrin, total organic carbon, and total suspended solids, sampling at the same time was not representative of the weekly mean; however, variability was observed between sites and constituents. For those constituent concentrations with significant differences seen between the two protocols, load adjustment factors (LAF) were determined, using a ratio of treatment means, and employed to adjust dry-season load estimates. Future work should include determining if LAF values can be used at similar sites excluded from the study or for similar constituents from the current sampling sites. PMID- 27192387 TI - Comparative study of ground water treatment plants sludges to remove phosphorous from wastewater. AB - Alum- and iron-based sludge obtained from water treatment plant produced during a unit treatment process (coagulation and flocculation) have been widely tested as a low-cost adsorbent to remove phosphorous (P) from wastewater. However, the effectiveness of iron-based sludge generated from the oxidation of iron which naturally occurs in the ground water has not been investigated. Moreover, influences of dominant metals ions comprised in the treatment plants sludges on P adsorption capacity and rate from wastewater are not yet known. This study, therefore, employed four different groundwater treatment plants sludges iron based (from the oxidation of iron) and alum-based (from coagulation and flocculation process) to determine their P adsorption capacities and adsorption rates from the synthetic wastewater (SWW) and secondary effluent wastewater (SEWW). Although metals ions concentrations were the highest in the iron-based sludge amongst the sludge used in this study, it appeared to have the lowest P adsorption capacity and adsorption rate. A good correlation between aluminium to iron mass ratio and adsorption capacity for both types of waters were noted. However, a poor relation between aluminium to iron mass ratio and adsorption rates for the SEWW was observed. Further, the tested sludges were found to have a better P removal efficiency and adsorption capacity from the SEWW than from the SWW. Thus, this study demonstrates the ground water treatment plants sludges could be a low cost and effective adsorbent in removing P from wastewater. PMID- 27192388 TI - Sex- and Site-Specific Normative Data Curves for HR-pQCT. AB - The purpose of this study was to develop age-, site-, and sex-specific centile curves for common high-resolution peripheral quantitative computed tomography (HR pQCT) and finite-element (FE) parameters for males and females older than 16 years. Participants (n = 866) from the Calgary cohort of the Canadian Multicentre Osteoporosis Study (CaMos) between the ages of 16 and 98 years were included in this study. Participants' nondominant radius and left tibia were scanned using HR pQCT. Standard and automated segmentation methods were performed and FE analysis estimated apparent bone strength. Centile curves were generated for males and females at the tibia and radius using the generalized additive models for location, scale, and shape (GAMLSS) package in R. After GAMLSS analysis, age-, sex-, and site-specific centiles (10th, 25th, 50th, 75th, 90th) for total bone mineral density and trabecular number as well as failure load have been calculated. Clinicians and researchers can use these reference curves as a tool to assess bone health and changes in bone quality. (c) 2016 American Society for Bone and Mineral Research. PMID- 27192389 TI - Management of Different Subtypes of Primary Angle Closure with Phacoemulsification and Viscogoniosynechialysis. AB - PURPOSE: To retrospectively assess the effectiveness of combined phacoemulsification with viscogoniosynechialysis for patients with different subtypes of primary angle closure (PAC). METHODS: Forty-three eyes of 37 patients diagnosed with PAC (12 eyes), PAC with glaucoma (PACG, 20 eyes), and acute PAC (11 eyes) were treated with phacoemulsification and viscogoniosynechialysis between November 2010 and October 2012. Main outcome measures were anterior chamber depth (ACD), intraocular pressure (IOP), the number of IOP-lowering medication, extent of peripheral anterior synechia (PAS), and visual acuity preoperatively and one month postoperatively. RESULTS: All operations were successfully accomplished and no intra-operative complications were observed. The ACD, IOP, PAS, and visual acuity were all significantly improved postoperatively, especially in the acute PAC group, which resulted in few glaucoma drugs being needed. The IOP was decreased into equal or less than 21 mmHg in most patients postoperatively, except four patients had IOP slightly higher than 21 mmHg. However, they were restored to normal spontaneously or by medication at last follow-up. The extent of PAS was all reduced to less than 90 or 180 degrees , with the visual acuity restored to more than 0.1. CONCLUSIONS: Combined phacoemulsification with viscogoniosynechialysis seems to be an effective surgical procedure in the treatment of various subtypes of PAC. PMID- 27192390 TI - Hearing impairment, cochlear morphology, and peroxynitrite (ONOO(-)) formation in adult and aging NOS II knockout mice. AB - CONCLUSION: Nitric oxide synthase (NOS) II induction is a protective mechanism against age-related degeneration of the cochlea. OBJECTIVES: An induction of NOS II has been described in different inner ear pathologies. The objective was to examine the role of NOS II in age-related degeneration of the cochlea. METHODS: The hearing ability in adult and aging NOS II knockout mice (KO) and their wildtype (WT) littermates was explored via auditory brainstem response (ABR) measurements. Inner ear morphological differences were studied with scanning electron microscopy (SEM). Immunohistochemistry was used to examine the induction of NOS II in the inner ear of aging WT mice. Expression of nitrotyrosin, a marker protein for the reactive oxygen species peroxynitrite, was compared between KO and WT mice using immunohistochemistry. RESULTS: Adult KO mice exhibited a mild hearing impairment. WT mice showed an induction of NOS II after 6 months of age. Age-related hearing deterioration was accelerated in KO mice, which was accompanied by increased nitrotyrosin formation and outer hair cell loss. PMID- 27192391 TI - MRI of cerebral blood flow under hyperbaric conditions in rats. AB - Hyperbaric oxygen (HBO) therapy has a number of clinical applications. However, the effects of acute HBO on basal cerebral blood flow (CBF) and neurovascular coupling are not well understood. This study explored the use of arterial spin labeling MRI to evaluate changes in baseline and forepaw stimulus-evoked CBF responses in rats (n = 8) during normobaric air (NB), normobaric oxygen (NBO) (100% O2 ), 3 atm absolute (ATA) hyperbaric air (HB) and 3 ATA HBO conditions. T1 was also measured, and the effects of changes in T1 caused by increasing oxygen on the CBF calculation were investigated. The major findings were as follows: (i) increased inhaled oxygen concentrations led to a reduced respiration rate; (ii) increased dissolved paramagnetic oxygen had significant effects on blood and tissue T1 , which affected the CBF calculation using the arterial spin labeling method; (iii) the differences in blood T1 had a larger effect than the differences in tissue T1 on CBF calculation; (iv) if oxygen-induced changes in blood and tissue T1 were not taken into account, CBF was underestimated by 33% at 3 ATA HBO, 10% at NBO and <5% at HB; (v) with correction, CBF values under HBO, HB and NBO were similar (p > 0.05) and all were higher than CBF under NB by ~40% (p < 0.05), indicating that hypercapnia from the reduced respiration rate masks oxygen-induced vasoconstriction, although blood gas was not measured; and (vi) substantial stimulus-evoked CBF increases were detected under HBO, similar to NB, supporting the notion that activation-induced CBF regulation in the brain does not operate through an oxygen-sensing mechanism. CBF MRI provides valuable insights into the effects of oxygen on basal CBF and neurovascular coupling under hyperbaric conditions. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27192392 TI - A Symmetric Eczematous Eruption Harboring Thousands of Melanocytic Lesions. AB - IMPORTANCE: The abrupt appearance of melanocytic lesions is a unique phenomenon that can occur in the setting of eruptive nevi or epidermotropic melanoma metastases. OBJECTIVE: To examine the immunohistochemical and genetic mutative features of a novel case of an eczematous reaction followed by the abrupt appearance of melanocytic lesions. DESIGN, SETTING, AND PARTICIPANT: Case report of a 48-year-old woman with no significant medical history who first presented with an eczematous dermatitis on her torso, extremities, and buttocks and who subsequently developed thousands of pinpoint, histologically atypical melanocytic tumors and invasive melanoma within the areas of inflammation. MAIN OUTCOMES AND MEASURES: Immunohistochemical and mutational analyses of the patient's melanocytic tumors were conducted. RESULTS: Mutational analysis of the pigmented lesions did not identify any activating mutations in BRAF, PTEN, NRAS, KRAS, and HRAS. Immunohistochemical analyses of 9 biopsied pigmented lesions all showed normal expression of the tumor suppressors p16 and PTEN and no expression of mutated BRAF V600E protein. CONCLUSIONS AND RELEVANCE: To our knowledge, this is a previously unreported eruption comprising 2 distinct components: an eczematous reaction and a wave of melanocytic proliferations within the inflammatory regions. Possible explanations for this patient's condition, include immune stimulation leading to nevogenesis, benign "nevic" metastases, eruptive nevi, and epidermotropic metastatic melanoma. PMID- 27192393 TI - Scarlet Fever Upsurge in England and Molecular-Genetic Analysis in North-West London, 2014. AB - Scarlet fever notifications surged across the United Kingdom in spring 2014. Molecular epidemiologic investigation of Streptococcus pyogenes infections in North-West London highlighted increased emm4 and emm3 infections coincident with the upsurge. Unlike outbreaks in other countries, antimicrobial resistance was uncommon, highlighting an urgent need to better understand the drivers of scarlet fever activity. PMID- 27192394 TI - National survey on concepts for congenital hypothyroidism screening in neonatal intensive care units in Japan. AB - BACKGROUND: Recently, a revised version of the Guidelines for Mass Screening of Congenital Hypothyroidism (CH) was published in Japan, but it is not known whether the guidelines are used routinely in neonatal intensive care units (NICU). METHODS: To clarify the current status and issues of newborn screening (NBS) for CH in Japanese NICU, we sent a questionnaire by mail or email to neonatologists responsible for 100 tertiary NICU in Japan, and analyzed their responses. RESULTS: The response rate was 92% (92/100). Among respondents, 65% (59/91) performed thyroid function testing separately from NBS for CH. Within this group, 63% (37/59) applied criteria, mostly for very low-birthweight (VLBW) infants (25/37). Only 29% of respondents (26/90), however, used criteria to select VLBW infants for treatment. Furthermore, criteria differed in each NICU. Fifty-seven percent of respondents (50/87) reported issues regarding NBS for CH in NICU, which fell into three main areas: establishment of a clear method for the management of VLBW infants; necessity of simultaneous measurement of thyroid stimulating hormone and free thyroxine; and overlapping blood collection for NBS and thyroid function tests. CONCLUSIONS: Two-thirds of tertiary NICU performed thyroid function testing separately from NBS for CH. Approximately 60% of neonatologists responded that current NBS for CH had ongoing issues. Further research is needed to establish the optimal NBS protocol for CH in NICU in Japan. PMID- 27192395 TI - Improved Global Capacity for Influenza Surveillance. AB - During 2004-2009, the Centers for Disease Control and Prevention (CDC) partnered with 39 national governments to strengthen global influenza surveillance. Using World Health Organization data and program evaluation indicators collected by CDC in 2013, we retrospectively evaluated progress made 4-9 years after the start of influenza surveillance capacity strengthening in the countries. Our results showed substantial increases in laboratory and sentinel surveillance capacities, which are essential for knowing which influenza strains circulate globally, detecting emergence of novel influenza, identifying viruses for vaccine selection, and determining the epidemiology of respiratory illness. Twenty-eight of 35 countries responding to a 2013 questionnaire indicated that they have leveraged routine influenza surveillance platforms to detect other pathogens. This additional surveillance illustrates increased health-system strengthening. Furthermore, 34 countries reported an increased ability to use data in decision making; data-driven decisions are critical for improving local prevention and control of influenza around the world. PMID- 27192397 TI - Comment on: "The Prevalence of Dry Eye and Sjogren Syndrome in Patients with Migraine". PMID- 27192396 TI - Absolute dosimetry on a dynamically scanned sample for synchrotron radiotherapy using graphite calorimetry and ionization chambers. AB - The absolute dose delivered to a dynamically scanned sample in the Imaging and Medical Beamline (IMBL) on the Australian Synchrotron was measured with a graphite calorimeter anticipated to be established as a primary standard for synchrotron dosimetry. The calorimetry was compared to measurements using a free air chamber (FAC), a PTW 31 014 Pinpoint ionization chamber, and a PTW 34 001 Roos ionization chamber. The IMBL beam height is limited to approximately 2 mm. To produce clinically useful beams of a few centimetres the beam must be scanned in the vertical direction. In practice it is the patient/detector that is scanned and the scanning velocity defines the dose that is delivered. The calorimeter, FAC, and Roos chamber measure the dose area product which is then converted to central axis dose with the scanned beam area derived from Monte Carlo (MC) simulations and film measurements. The Pinpoint chamber measures the central axis dose directly and does not require beam area measurements. The calorimeter and FAC measure dose from first principles. The calorimetry requires conversion of the measured absorbed dose to graphite to absorbed dose to water using MC calculations with the EGSnrc code. Air kerma measurements from the free air chamber were converted to absorbed dose to water using the AAPM TG-61 protocol. The two ionization chambers are secondary standards requiring calibration with kilovoltage x-ray tubes. The Roos and Pinpoint chambers were calibrated against the Australian primary standard for air kerma at the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA). Agreement of order 2% or better was obtained between the calorimetry and ionization chambers. The FAC measured a dose 3-5% higher than the calorimetry, within the stated uncertainties. PMID- 27192398 TI - Cationic Polyphosphazene Vesicles for Cancer Immunotherapy by Efficient in Vivo Cytokine IL-12 Plasmid Delivery. AB - To circumvent the severe toxicity of the systemic delivery of IL-12 protein and the limits of local administration of IL-12 gene, we constructed a polymersome system for systemic delivery of recombinant murine IL-12 plasmid (pmIL-12) based on amphiphilic polyphosphazenes containing weakly cationic N,N diisopropylethylenediamine (DPA) as hydrophobic groups and monomethoxy poly(ethylene glycol) (mPEG) as hydrophilic tails. By simple dialysis method, pmIL-12 was successfully loaded into polymersomes due to the combination effect of physical encapsulation and electrostatic interaction. This pmIL-12 polymersome delivery system was validated with good biocompatibility and stability despite of serum protein and DNase challenging. The results of in vivo antitumor experiments showed that intravenous injection of pmIL-12 polymersomes achieved significant suppression of tumor growth in BALB/c mice bearing CT-26 colon carcinoma. The analysis revealed that the mechanism was related to the antitumor immune response induced by efficient transfection of pmIL-12 polymersomes, which maybe involved lymphocytes infiltration and angiogenic inhibition at the tumor site. PMID- 27192399 TI - Facile Fabrication of MoS2-Modified SnO2 Hybrid Nanocomposite for Ultrasensitive Humidity Sensing. AB - An ultrasensitive humidity sensor based on molybdenum-disulfide- (MoS2)-modified tin oxide (SnO2) nanocomposite has been demonstrated in this work. The nanostructural, morphological, and compositional properties of an as-prepared MoS2/SnO2 nanocomposite were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), energy dispersive spectrometry (EDS), nitrogen sorption analysis, and Raman spectroscopy, which confirmed its successful preparation and rationality. The sensing characteristics of the MoS2/SnO2 hybrid film device against relative humidity (RH) were investigated at room temperature. The RH sensing results revealed an unprecedented response, ultrafast response/recovery behaviors, and outstanding repeatability. To our knowledge, the sensor response yielded in this work was tens of times higher than that of the existing humidity sensors. Moreover, the MoS2/SnO2 hybrid nanocomposite film sensor exhibited great enhancement in humidity sensing performances as compared to the pure MoS2, SnO2, and graphene counterparts. Furthermore, complex impedance spectroscopy and bode plots were employed to understand the underlying sensing mechanisms of the MoS2/SnO2 nanocomposite toward humidity. The synthesized MoS2/SnO2 hybrid composite was proved to be an excellent candidate for constructing ultrahigh performance humidity sensor toward various applications. PMID- 27192400 TI - Substance Use Patterns Among Adolescents in Europe: A Latent Class Analysis. AB - BACKGROUND: Several researchers have investigated substance use patterns using a latent class analysis; however, hardly no studies exist on substance use patterns across countries. OBJECTIVES: Adolescent substance use patterns, demographic factors, and international differences in the prevalence of substance use patterns were explored. METHODS: Data from 25 European countries were used to identify patterns of adolescent (12-16 years, 50.6% female) substance use (N = 33,566). RESULTS: Latent class analysis revealed four substance use classes: nonusers (68%), low-alcohol users (recent use of beer, wine, and alcopops; 16.1%), alcohol users (recent use of alcohol and lifetime use of marijuana; 11.2%), and polysubstance users (recent use of alcohol, marijuana, and other illicit drugs; 4.7%). Results support a general pattern of adolescent substance use across all countries; however, the prevalence rates of use patterns vary for each country. CONCLUSIONS/IMPORTANCE: The present research provides insight into substance use patterns across Europe by using a large international adolescent sample, multidimensional indicators and a variety of substances. Substance use patterns are helpful when targeting policy and prevention strategies. PMID- 27192401 TI - Risk Minimization and a Late Holocene Increase in Mobility at Roonka Flat, South Australia: An Analysis of Lower Limb Bone Diaphyseal Shape. AB - OBJECTIVES: The strengthening of the El Nino Southern Oscillation (ENSO) in the mid-Holocene caused significant changes in climate, vegetation, and faunal assemblages in South Australia. The appearance of a light, flexible backed artifact toolkit ~4 kya has been interpreted as evidence for changes in foraging behavior in response to this event. Optimal foraging theory supports a risk minimization strategy for South Australian hunter-gatherers in which increased mobility was used to cope with effects of a dryer, unstable environment in the late Holocene. Whether this event caused changes in foraging mobility will be tested by examining lower limb external diaphyseal shape between pre-ENSO and post-ENSO skeletons from Roonka Flat, South Australia. MATERIALS AND METHODS: Anteroposterior and mediolateral diameters were used to construct diaphyseal shape indices for Roonka Flat femora and tibiae. If populations living in South Australia became more mobile over time, then post-ENSO skeletons should exhibit higher shape indices. RESULTS: The pooled-sex post-ENSO sample has significantly higher femoral shape indices than the pre-ENSO sample. Males do not show significant diaphyseal shape differences over time, but females significantly increase. DISCUSSION: These data are consistent with the risk minimization model, indicating that South Australians became more mobile post-ENSO to better exploit a less productive environment by expanding their foraging radii. The temporal shift toward more elliptical diaphyses is more notable in females than males, which is consistent with Aboriginal ethnographies that show both sexes being intensely involved in hunting and capturing game animals. Am J Phys Anthropol 161:94-103, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27192402 TI - Cyc17, a meiosis-specific cyclin, is essential for anaphase initiation and chromosome segregation in Tetrahymena thermophila. AB - Although the role of cyclins in controlling nuclear division is well established, their function in ciliate meiosis remains unknown. In ciliates, the cyclin family has undergone massive expansion which suggests that diverse cell cycle systems exist, and this warrants further investigation. A screen for cyclins in the model ciliate Tetrahymena thermophila showed that there are 34 cyclins in this organism. Only 1 cyclin, Cyc17, contains the complete cyclin core and is specifically expressed during meiosis. Deletion of CYC17 led to meiotic arrest at the diakinesis-like metaphase I stage. Expression of genes involved in DNA metabolism and chromosome organization (chromatin remodeling and basic chromosomal structure) was repressed in cyc17 knockout matings. Further investigation suggested that Cyc17 is involved in regulating spindle pole attachment, and is thus essential for chromosome segregation at meiosis. These findings suggest a simple model in which chromosome segregation is influenced by Cyc17. PMID- 27192404 TI - Perfluoroalkyl Acids (PFAAs) and Selected Precursors in the Baltic Sea Environment: Do Precursors Play a Role in Food Web Accumulation of PFAAs? AB - The present study examined the presence of perfluoroalkyl acids (PFAAs) and selected precursors in the Baltic Sea abiotic environment and guillemot food web, and investigated the relative importance of precursors in food web accumulation of PFAAs. Sediment, water, zooplankton, herring, sprat, and guillemot eggs were analyzed for perfluoroalkane sulfonic acids (PFSAs; C4,6,8,10) and perfluoroalkyl carboxylic acids (PFCAs; C6-15) along with six perfluoro-octane sulfonic acid (PFOS) precursors and 11 polyfluoroalkyl phosphoric acid diesters (diPAPs). FOSA, FOSAA and its methyl and ethyl derivatives (Me- and EtFOSAA), and 6:2/6:2 diPAP were detected in sediment and water. While FOSA and the three FOSAAs were detected in all biota, a total of nine diPAPs were only detected in zooplankton. Concentrations of PFOS precursors and diPAPs exceeded PFOS and PFCA concentrations, respectively, in zooplankton, but not in fish and guillemot eggs. Although PFOS precursors were present at all trophic levels, they appear to play a minor role in food web accumulation of PFOS based on PFOS precursor/PFOS ratios and PFOS and FOSA isomer patterns. The PFCA pattern in fish could not be explained by the intake pattern based on PFCAs and analyzed precursors, that is, diPAPs. Exposure to additional precursors might therefore be a dominant exposure pathway compared to direct PFCA exposure for fish. PMID- 27192403 TI - Titanium-Silver Alloy Miniplates for Mandibular Fixation: In Vitro and In Vivo Study. AB - PURPOSE: Titanium (Ti) alloys have received considerable attention as materials for oral and maxillofacial surgery, which require high mechanical strength, osteosynthesis, and biocompatibility. The objective was to implant miniplates fabricated from commercially pure Ti (CP Ti) and newly developed Ti-silver (Ag) alloy in fractured mandibles of adult dogs after preliminary mechanical and biological characterization. MATERIALS AND METHODS: The surface characteristics, biocompatibility, and pre-osteoblast adhesion and proliferation of CP Ti (grade 3) and Ti-Ag (2 at% Ag) alloys were evaluated. Next, the bending strength of 6- and 8-hole miniplates fabricated from CP Ti and Ti-Ag was compared according to ISO (International Organization for Standardization) 9585. Six-hole miniplates were implanted for 12 weeks in fractured mandibles of adult dogs. The Ag ion concentration in each alloy and implanted bone block with soft tissue was measured by inductively coupled plasma mass spectroscopy after euthanasia according to ISO 10993-12. RESULTS: Precipitated Ag was detected in Ti-Ag by alpha- and beta-phase Ti in x-ray powder diffraction. The biocompatibility with pre-osteoblasts of Ti-Ag and CP Ti was comparable in terms of cytotoxicity, cell adhesion, and proliferation (P > .05). Ti-Ag miniplates had up to 3-fold greater bending strength than CP Ti miniplates (P < .05). An in vivo study showed that CP Ti and Ti-Ag miniplates had comparable soft and hard tissue regeneration ability (P > .05). Ag ions were detected in Ti-Ag alloys and applied mandible blocks. CONCLUSIONS: The results of this study suggest that Ti-Ag alloys can be used to produce miniplates with high mechanical properties, as well as considerable biocompatibility, osteosynthesis ability, and Ag ion-release properties. Further studies, including preclinical investigations, are required to enable clinical use of Ti-Ag bone plates. PMID- 27192406 TI - Concentration and dissipation of chlorantraniliprole and thiamethoxam residues in maize straw, maize, and soil. AB - To study the dissipation rates and final residual levels of chlorantraniliprole and thiamethoxam in maize straw, maize, and soil, two independent field trials were conducted during the 2014 cropping season in Beijing and Anhui Provinces of China. A 40% wettable powder (20% chlorantraniliprole + 20% thiamethoxam) was sprayed onto maize straw and soil at an application rate of 118 g of active ingredient per hectare (g a.i.ha(-1)). The residual concentrations were determined by ultra-high-performance liquid chromatography-tandem mass spectrometry. The chlorantraniliprole half-lives in maize straw and soil were 9.0 10.8 and 9.5-21.7 days, respectively. The thiamethoxam half-lives in maize straw and soil were 8.4-9.8 and 4.3-11.7 days, respectively. The final residues of chlorantraniliprole and thiamethoxam in maize straw, maize, and soil were measured after the pesticides had been sprayed two and three times with an interval of 7 days using 1 and 1.5 times the recommended rate (72 g a.i. ha(-1) and 108 g a.i. ha(-1), respectively). Representative maize straw, maize, and soil samples were collected after the last treatment at pre-harvest intervals of 7, 14, and 28 days. The chlorantraniliprole residue was below 0.01 mg kg(-1) in maize, between 0.01 and 0.31 mg kg(-1) in maize straw, and between 0.03 and 1.91 mg kg(-1) in soil. The thiamethoxam residue concentrations in maize, maize straw, and soil were <0.01, <0.01, and 0.01-0.03 mg kg(-1), respectively. The final pesticide residues on maize were lower than the maximum residue limit (MRL) of 0.02 mg kg(-1) after a 14-day pre-harvest interval. Therefore, a dosage of 72 g a.i. ha(-1) was recommended, as it can be considered safe to human beings and animals. PMID- 27192407 TI - Diet and Macronutrient Optimization in Wild Ursids: A Comparison of Grizzly Bears with Sympatric and Allopatric Black Bears. AB - When fed ad libitum, ursids can maximize mass gain by selecting mixed diets wherein protein provides 17 +/- 4% of digestible energy, relative to carbohydrates or lipids. In the wild, this ability is likely constrained by seasonal food availability, limits of intake rate as body size increases, and competition. By visiting locations of 37 individuals during 274 bear-days, we documented foods consumed by grizzly (Ursus arctos) and black bears (Ursus americanus) in Grand Teton National Park during 2004-2006. Based on published nutritional data, we estimated foods and macronutrients as percentages of daily energy intake. Using principal components and cluster analyses, we identified 14 daily diet types. Only 4 diets, accounting for 21% of days, provided protein levels within the optimal range. Nine diets (75% of days) led to over-consumption of protein, and 1 diet (3% of days) led to under-consumption. Highest protein levels were associated with animal matter (i.e., insects, vertebrates), which accounted for 46-47% of daily energy for both species. As predicted: 1) daily diets dominated by high-energy vertebrates were positively associated with grizzly bears and mean percent protein intake was positively associated with body mass; 2) diets dominated by low-protein fruits were positively associated with smaller-bodied black bears; and 3) mean protein was highest during spring, when high-energy plant foods were scarce, however it was also higher than optimal during summer and fall. Contrary to our prediction: 4) allopatric black bears did not exhibit food selection for high-energy foods similar to grizzly bears. Although optimal gain of body mass was typically constrained, bears usually opted for the energetically superior trade-off of consuming high-energy, high-protein foods. Given protein digestion efficiency similar to obligate carnivores, this choice likely supported mass gain, consistent with studies showing monthly increases in percent body fat among bears in this region. PMID- 27192405 TI - Sensitivity of the Dengue Surveillance System in Brazil for Detecting Hospitalized Cases. AB - We evaluated the sensitivity of the dengue surveillance system in detecting hospitalized cases in ten capital cities in Brazil from 2008 to 2013 using a probabilistic record linkage of two independent information systems hospitalization (SIH-SUS) adopted as the gold standard and surveillance (SINAN). Sensitivity was defined as the proportion of cases reported to the surveillance system amid the suspected hospitalized cases registered in SIH-SUS. Of the 48,174 hospitalizations registered in SIH-SUS, 24,469 (50.7%) were reported and registered in SINAN, indicating an overall sensitivity of 50.8% (95%CI 50.3 51.2). The observed sensitivity for each of the municipalities included in the study ranged from 22.0% to 99.1%. The combination of the two data sources identified 71,161 hospitalizations, an increase of 97.0% over SINAN itself. Our results allowed establishing the proportion of underreported dengue hospitalizations in the public health system in Brazil, highlighting the use of probabilistic record linkage as a valuable tool for evaluating surveillance systems. PMID- 27192408 TI - Statolith Morphometrics Can Discriminate among Taxa of Cubozoan Jellyfishes. AB - Identification of potentially harmful cubomedusae is difficult due to their gelatinous nature. The only hard structure of medusae, the statolith, has the potential to provide robust measurements for morphometric analysis. Traditional morphometric length to width ratios (L: W) and modern morphometric Elliptical Fourier Analysis (EFA) were applied to proximal, oral and lateral statolith faces of 12 cubozoan species. EFA outperformed L: W as L: W did not account for the curvature of the statolith. Best discrimination was achieved with Canonical Discriminant Analysis (CDA) when analysing proximal + oral + lateral statolith faces in combination. Normalised Elliptical Fourier (NEF) coefficients classified 98% of samples to their correct species and 94% to family group. Statolith shape agreed with currently accepted cubozoan taxonomy. This has potential to assist in identifying levels of risk and stock structure of populations in areas where box jellyfish envenomations are a concern as the severity of envenomation is family dependent. We have only studied 12 (27%) of the 45 currently accepted cubomedusae, but analyses demonstrated that statolith shape is an effective taxonomic discriminator within the Class. PMID- 27192409 TI - Access to Interdental Brushing in Periodontal Healthy Young Adults: A Cross Sectional Study. AB - PURPOSE: Interdental diameter space is largely undefined in adults, which compromises the decision support for daily interdental cleaning during routine practice in individual oral prophylaxis. This study assesses the distribution of diameter access of interdental spaces in an 18- to 25-year-old adult population free of periodontal disease. METHODS: In March-April 2015, a cross-sectional study using random sampling was performed at the University Lyon 1, France. The interproximal dental spaces of 99 individuals were examined using a colorimetric calibrated probe associated with the corresponding calibrated interdental brush (IDB). RESULTS: Of the 2,408 out of 2,608 sites, the overall accessibility prevalence of any interdental brushing was 92.3%. In total, 80.6% of the sites required interdental brushes with smaller diameters (0.6-0.7 mm). In anterior sites, the diameter of the interdental brushes used was smaller (55.8% of IDB with 0.6 mm) than the diameter of the interdental brushes used in posterior sites (26.1% of IDB with 0.6 mm) (p < 0.01). The adjusted ORs indicate a significant association with the location of the sites (approximately doubling the risk of bleeding, i.e., OR = 1.9, in posterior sites). CONCLUSIONS: Most interdental sites can be cleaned using interdental brushes. Even in healthy people, interdental hygiene requirements are very high. Strengthening the oral hygiene capacity by specifically using interdental brushes can have an effect on the health of the entire population. Screening of the accessibility of the interdental space should be a component of a routine examination for all patients. PMID- 27192410 TI - A Centrosymmetric Hexagonal Magnet with Superstable Biskyrmion Magnetic Nanodomains in a Wide Temperature Range of 100-340 K. AB - Superstable biskyrmion magnetic nanodomains are experimentally observed for the first time in a hexagonal MnNiGa, a common and easily produced centrosymmetric material. The biskyrmion states in MnNiGa thin plates, as determined by the combination of in situ Lorentz transmission electron microscopy images, magnetoresistivity, and topological Hall effect measurements, are surprisingly stable over a broad temperature range of 100-340 K. PMID- 27192411 TI - Correction: Single Sustained Inflation followed by Ventilation Leads to Rapid Cardiorespiratory Recovery but Causes Cerebral Vascular Leakage in Asphyxiated Near-Term Lambs. AB - [This corrects the article DOI: 10.1371/journal.pone.0146574.]. PMID- 27192412 TI - Participants' perceptions of an intervention implemented in an Action Research Nursing Documentation Project. AB - AIMS AND OBJECTIVES: The aim of this study is to describe healthcare professionals' experiences and perceptions of an intervention implemented in an action research project conducted to improve nursing documentation practices in four municipalities in Norway. BACKGROUND: Documentation of individualized patient care is a continuing concern in healthcare services and could impacts the quality and safety of healthcare. Use of electronic systems has made some aspects of documentation more comprehensive, but creation of an individualized care plan remains a pressing issue. DESIGN: A qualitative descriptive design was used. METHODS: An action research project was conducted between 2010-2012 to improve the content and quality of nursing documentation in community healthcare services in four municipalities. One year after the project was completed four focus group interviews were conducted with healthcare professionals, one for each involved municipality. Two unit managers were interviewed individually. Qualitative content analysis was used. RESULTS: Three themes emerged: healthcare professionals perceived competing interest; they experienced that they had to manage complexity and changes; and they highlighted a clear and visible leader as important for success. CONCLUSIONS: Quality improvement activities are essential. Healthcare professionals experience a complicated situation when electronic health record systems do not support workflow. Further research is recommended to focus on the functionality and user interface of electronic health record systems, and on the role of leadership when implementing changes in clinical practice. RELEVANCE TO CLINICAL PRACTICE: Stronger cooperation among policymakers, electronic health record system vendors, and healthcare professionals is essential for improving electronic health record systems and documentation practices. Involvement of end-users in these improvements can make a difference in the way the systems are perceived in the clinical workflow. PMID- 27192413 TI - Health-related quality of life as a predictor of mortality in patients on peritoneal dialysis. AB - OBJECTIVE: to characterize deaths that occurred, and the association between socio-demographic, clinical, laboratory variables and health-related quality of life and the outcome of death in patients on peritoneal dialysis, over a two year period after an initial assessment. METHOD: observational, prospective population study with 82 patients on peritoneal dialysis. The instruments used for the first stage of data collection were the mini-mental state examination, a sociodemographic, economic, clinical and laboratory questionnaire and the Kidney Disease and Quality of Life-Short Form. After two years, data for characterization and occurrence of death in the period were collected. The relative risk of death outcome was calculated through statistical analysis; the risk of death was estimated by the survival Kaplan-Meier curve, and determined predictors of death by the Cox Proportional Hazards Model. RESULTS: of the 82 original participants, 23 had as an outcome death within two years. The increased risk for the outcome of death was associated with a lower mean score of health related quality of life in the physical functioning domain. CONCLUSION: the worst health-related quality of life in the physical functioning domain, could be considered a predictor of death. PMID- 27192414 TI - Quality of life of Brazilian and Spanish cancer patients undergoing chemotherapy: an integrative literature review. AB - OBJECTIVE: characterize the scientific production of Brazil and Spain in regard to methodological aspects and aspects of health-related quality of life experienced by cancer patients receiving chemotherapy in both countries. METHOD: integrative literature review was conducted using the following databases: CINAHL, MEDLINE, SCOPUS and CUIDEN and the electronic libraries PubMed and SciELO, conducted in September 2013. RESULTS: a total of 28 papers met the inclusion criteria. The synthesis of knowledge was presented in three categories of analysis: assessment of quality of life in different types of cancer; sociodemographic factors that influenced quality of life; and type of cancer and interventions that improve quality of life. Chemotherapy affects health-related quality of life and the most important factors were: age, sex, chemotherapy protocol, type of surgery, stage of the disease, educational level, and emotional intelligence. Complementary therapies such as acupuncture, guided visualization, prayers and exercise were positive and reduced side effects. CONCLUSION: the results showed a poor level of evidence, since 86% of the studies were cross sectional descriptive studies; the instrument most frequently used to measure health-related quality of life was EORTC QLQ C-30 and more studies were conducted in Brazil than in Spain. PMID- 27192415 TI - Prediction of risk and incidence of dry eye in critical patients. AB - OBJECTIVES: to estimate the incidence of dry eye, to identify risk factors and to establish a risk prediction model for its development in adult patients admitted to the intensive care unit of a public hospital. METHOD: concurrent cohort, conducted between March and June, 2014, with 230 patients admitted to an intensive care unit. Data were analyzed by bivariate descriptive statistics, with multivariate survival analysis and Cox regression. RESULTS: 53% out of 230 patients have developed dry eye, with onset mean time of 3.5 days. Independent variables that significantly and concurrently impacted the time for dry eye to occur were: O2 in room air, blinking more than five times per minute (lower risk factors) and presence of vascular disease (higher risk factor). CONCLUSION: dry eye is a common finding in patients admitted to adults intensive care units, and care for its prevention should be established. PMID- 27192417 TI - Adaptation and evaluation of the measurement properties of the Brazilian version of the Self-efficacy for Appropriate Medication Adherence Scale. AB - OBJECTIVES: to undertake the cultural adaptation of, and to evaluate the measurement properties of, the Brazilian version of the Self-efficacy for Appropriate Medication Adherence Scale in coronary heart disease (CHD) patients, with outpatient monitoring at a teaching hospital. METHOD: the process of cultural adaptation was undertaken in accordance with the international literature. The data were obtained from 147 CHD patients, through the application of the sociodemographic/clinical characterization instrument, and of the Brazilian versions of the Morisky Self-Reported Measure of Medication Adherence Scale, the General Perceived Self-Efficacy Scale, and the Self-efficacy for Appropriate Medication Adherence Scale. RESULTS: the Brazilian version of the Self-efficacy for Appropriate Medication Adherence Scale presented evidence of semantic-idiomatic, conceptual and cultural equivalencies, with high acceptability and practicality. The floor effect was evidenced for the total score and for the domains of the scale studied. The findings evidenced the measure's reliability. The domains of the Brazilian version of the Self-efficacy for Appropriate Medication Adherence Scale presented significant inverse correlations of moderate to strong magnitude between the scores of the Morisky scale, indicating convergent validity, although correlations with the measure of general self-efficacy were not evidenced. The validity of known groups was supported, as the scale discriminated between "adherents" and "non-adherents" to the medications, as well as to "sufficient dose" and "insufficient dose". CONCLUSION: the Brazilian version of the Self-efficacy for Appropriate Medication Adherence Scale presented evidence of reliability and validity in coronary heart disease outpatients. PMID- 27192416 TI - Adherence to antiretrovirals in people coinfected with the human immunodeficiency virus and tuberculosis. AB - OBJECTIVE: assess the adherence levels to antiretroviral therapy in people coinfected with HIV/tuberculosis and correlate these levels with the sociodemographic and clinical variables of the study population. METHOD: cross sectional study involving 74 male and female adults coinfected with HIV/tuberculosis. For the data collection, a sociodemographic and clinical assessment form and the Antiretroviral Treatment Adherence Assessment Questionnaire were used. For the data analysis, the software STATA version 11 was used, through descriptive statistics, Fisher's chi-square exact test and the probability test. RESULTS: men were predominant (79.7%), between 30 and 39 years of age (35.1%), low income (75.7%) and pulmonary tuberculosis (71.6%). Adherence to antiretroviral therapy was inappropriate in 78.1% of the men; 61.0% of single people; 47.0% unemployed and 76.5% among people gaining less than one minimum wage. A significant difference was observed between compliance and length of use of antiretrovirals (p=0.018), sexual orientation (p=0.024) and number of children (p=0.029). CONCLUSION: the coinfected patients presented inappropriate adherence to the antiretrovirals, a fact that negatively affects the health conditions of the people living with HIV/tuberculosis coinfection. A statistically significant correlation was found between the levels of adherence and some sociodemographic and clinical characteristics. PMID- 27192418 TI - Guidelines for a Comprehensive Care Program to Ostomized Patients and Families: a Nursing proposal. AB - OBJECTIVES: describe care needs and demands that mark the discursive practices of ostomized clients and family members and discuss guidelines for a comprehensive care program to ostomized clients and their families, organized by macrosociological categories. METHOD: Creative and Sensitive, involving 17 ostomized subjects and family members at a municipal outpatient clinic. The ethical aspects were complied with. A characterization form was used, as well as Creativity and Sensitivity Dynamics: "speaking map", "body-knowledge" and "calendar". Critical Discourse Analysis was applied. RESULTS: the health needs and care demands of the ostomized patients and their family members, in their multiple dimensions, were constituted in the home and community, outpatient and social context, implying new orientations for nursing care. The unveiling of the data brought elements that constituted guidelines, in a macrosociological approach, to achieve the expanded integrality of nursing care. CONCLUSION: the ostomized clients are unique in their genre/peculiar from Latin sui generis, calling for strategies that respond to and distinguish their specificities. Elaborating a Public Health Policy that improves and reorganizes the care demands, taking into account these individual biopsychosocial and spiritual aspects, is a possible and irrevocable target in the attempt to achieve better conditions of health and wellbeing. PMID- 27192419 TI - Paramagnetic Gd(3+) labeled red blood cells for magnetic resonance angiography. AB - Despite significant advances in contrast enhanced-magnetic resonance angiography, the lack of truly blood-pool agents with long circulating property is limiting the clinical impact of this imaging technique. The terminal half-life for blood elimination of most small molecular weight gadolinium (Gd) based extracellular fluid agents is about 1.5 h when administered intravenously to subjects with normal renal function. The small size of these extracellular fluid agents does not prevent them from extravasating, especially from damaged vessels which are generally hyperpermeable. Therefore, the development of novel, clinically relevant blood pool contrast agents is critically needed to improve outcomes in the prevention, detection, and treatment of vascular diseases. We have demonstrated the fusion strategies in which the Gd-liposome without any stealth property radically fuses with red blood cells (RBCs) forming MR glowing Gd-RBC with the order of magnitude enhancements in circulation half-life (t1/2 = 50 h) and r1 relaxivity (r1 = 19.0 mM(-1) s(-1)) of Gd. The in vivo contrast enhancement of Gd-RBC was studied by using 3T clinical MR scanner for extended period of time, which clearly visualized the abdominal aorta. In summary, the vascular delivery of blood pool agents may benefit from carriage by RBCs because it naturally stays within the vascular lumen. PMID- 27192420 TI - Targeting dendritic cells in lymph node with an antigen peptide-based nanovaccine for cancer immunotherapy. AB - The design of peptide-based subunit vaccine formulations for the direct delivery of tumor antigen peptides (Aps) to dendritic cells (DCs) localized within draining lymph nodes (DLNs) is challenging. Mature DCs (mDCs) are abundantly distributed within DLNs but have dramatically reduced endocytic uptake and antigen-processing abilities, so their role as potential vaccine targets has been largely overlooked. Here we report an ultra-small biocompatible nanovaccine (alpha-Ap-FNP) functionalized by avidly targeting delivery of Ap via the scavenger receptor class B1 (SR-B1) pathway to mDCs. The self-assembly, small size (~30 nm), SR-B1-targeting and optical properties of alpha-Ap-FNP resulted in its efficient Ap loading, substantial LN accumulation, targeting of mDCs and enhanced Ap presentation, and fluorescence trafficking, respectively. We also demonstrate that the alpha-Ap-FNP can be either used alone or encapsulated with CpG oligodeoxynucleotide as a prophylactic and therapeutic vaccine. Thus, the excellent properties of alpha-Ap-FNP provide it potential for clinical applications as a potent nanovaccine for cancer immunotherapy. PMID- 27192421 TI - MMP-9 triggered self-assembly of doxorubicin nanofiber depots halts tumor growth. AB - A central challenge in cancer care is to ensure that therapeutic compounds reach their targets. One approach is to use enzyme-responsive biomaterials, which reconfigure in response to endogenous enzymes that are overexpressed in diseased tissues, as potential site-specific anti-tumoral therapies. Here we report peptide micelles that upon MMP-9 catalyzed hydrolysis reconfigure to form fibrillar nanostructures. These structures slowly release a doxorubicin payload at the site of action. Using both in vitro and in vivo models, we demonstrate that the fibrillar depots are formed at the sites of MMP-9 overexpression giving rise to enhanced efficacy of doxorubicin, resulting in inhibition of tumor growth in an animal model. PMID- 27192422 TI - The rites of spring, Take 2. AB - Recruiting PhD students can be a frustrating process, but Eve Marder looks forward to welcoming the latest crop in the autumn. PMID- 27192423 TI - New Insights on Different Response of MDMA-Elicited Serotonin Syndrome to Systemic and Intracranial Administrations in the Rat Brain. AB - In spite of the fact that systemic administration of MDMA elicits serotonin syndrome, direct intracranial administration fails to reproduce the effect. To reconcile these findings, it has been suggested that the cause of serotonin syndrome is attributed mainly to MDMA hepatic metabolites, and less likely to MDMA itself. Recently, however, this explanation has been challenged, and alternative hypotheses need to be explored. Here, we tested the hypothesis that serotonin syndrome is the result of excessive 5HT simultaneously in many brain areas, while MDMA administered intracranially fails to cause serotonin syndrome because it produces only a localized effect at the delivery site and not to other parts of the brain. This hypothesis was examined using adult male Sprague Dawley rats by comparing 5HT responses in the right and left hemispheric frontal cortices, right and left hemispheric diencephalons, and medullar raphe nucleus. Occurrence of serotonin syndrome was confirmed by measuring change in body temperature. Administration routes included intraperitoneal (IP), intracerebroventricular (ICV) and reverse microdialysis. First, we found that IP administration caused excessive 5HT in all five sites investigated and induced hypothermia, suggesting the development of the serotonin syndrome. In contrast, ICV and reverse microdialysis caused excessive 5HT only in regions of delivery sites without changes in body-core temperature, suggesting the absence of the syndrome. Next, chemical dyes were used to trace differences in distribution and diffusion patterns between administration routes. After systemic administration, the dyes were found to be evenly distributed in the brain. However, the dyes administered through ICV or reverse microdialysis injection still remained in the delivery sites, poorly diffusing to the brain. In conclusion, intracranial MDMA administration in one area has no or little effect on other areas, which must be considered a plausible reason for the difference in MDMA-elicited serotonin syndrome between systemic and intracranial administrations. PMID- 27192425 TI - Clinical, autoimmune, and psychiatric parameters correlate with sleep disturbance in patients with systemic sclerosis and rheumatoid arthritis. AB - OBJECTIVES: Sleep disturbance is an important contributor to poor quality of life in rheumatic disorders. This study aims to test whether clinical, autoimmune and psychological factors are associated with sleep disturbance in systemic sclerosis (SSc) compared to rheumatoid arthritis (RA) patients and controls. METHODS: 101 female subjects (SSc=33, RA=34, healthy controls=34) participated in this observational, cross-sectional, parallel group study. Sleep disturbance was assessed with the Pittsburgh Sleep Quality Index (PSQI). Other assessments included the visual analogue scale (VAS) for pain, 36-item Short-Form Health Survey (SF-36), Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI). Clinical parameters, therapeutic regimen, and serologic status were recorded. RESULTS: In SSc patients, PSQI scores were higher than in RA patients and controls. Linear regression analysis showed that in SSc patients PSQI scores was associated with BDI, disease duration, modified Rodnan skin score and VAS, while DAS28 and BDI were associated with PSQI scores in RA patients. Anti-Scl70 and ANA positive SSc patients showed higher PSQI scores compared to those ANA positive only, while no differences were observed in RA patients classified according to rheumatoid factor positivity. SSc patients treated with immunosuppressants had lower PSQI scores compared to those not on therapy, whereas only corticosteroid treatment was significantly associated with higher PSQI scores in RA patients. RA patients with disease activity higher than moderate (DAS28>=3.2) had higher PSQI scores than those with lower than moderate (DAS28<3.2). CONCLUSIONS: Longitudinal studies are needed to identify disease specific patterns associated with sleep disturbances and the influence on sleep function induced by immunosuppressive therapy among rheumatic patients. PMID- 27192426 TI - Synthesis and biological evaluation of 3beta-androsta-5,8(14),15-trien-17-one derivatives as potential anticancer agents. AB - A novel and operationally simple method for highly efficient synthesis of promising anti-cancer 3beta-hydroxy-16-arylandrosta-5,8(14),15-trien-17-ones was reported. Compounds were tested for their cytotoxic activities against A549, SKOV3, MKN-45 and MDA-MB-435 cancer cell lines. The preliminary results showed that compounds 5e, g were the most active especially against cancer cell lines tested. PMID- 27192424 TI - Spatial and Temporal Dynamics of a Mortality Event among Central African Great Apes. AB - In 2006-2007 we observed an unusual mortality event among apes in northern Republic of Congo that, although not diagnostically confirmed, we believe to have been a disease outbreak. In 2007-2011 we conducted ape nest surveys in the region, recording 11,835 G. g. gorilla nests (2,262 groups) and 5,548 P. t. troglodytes nests (2,139 groups). We developed a statistical model to determine likely points of origin of the outbreak to help identify variables associated with disease emergence and spread. We modeled disease spread across the study area, using suitable habitat conditions for apes as proxy for local ape densities. Infectious status outputs from that spread model were then used alongside vegetation, temperature, precipitation and human impact factors as explanatory variables in a Generalized Linear Model framework to explain observed 2007-2011 ape nest trends in the region. The best models predicted emergence in the western region of Odzala-Kokoua National Park and north of the last confirmed Ebola virus disease epizootics. Roads were consistently associated with attenuation of modeled virus spread. As disease is amongst the leading threats to great apes, gaining a better understanding of disease transmission dynamics in these species is imperative. Identifying ecological drivers underpinning a disease emergence event and transmission dynamics in apes is critical to creating better predictive models to guide wildlife management, develop potential protective measures for wildlife and to reduce potential zoonotic transmission to humans. The results of our model represent an important step in understanding variables related to great ape disease ecology in Central Africa. PMID- 27192427 TI - Synthesis of 3alpha-deuterated 7alpha-hydroxy-DHEA and 7-oxo-DHEA and application in LC-MS/MS plasma analysis. AB - 7-Oxygenated metabolites of dehydroepiandrosterone (DHEA) are known for their neuroprotective and immunomodulatory properties. These neuroactive steroids are currently predominately analysed by mass spectrometry, for which the use of internal deuterated standards is necessary. The aim of this study was to synthesize the deuterated derivatives of 7alpha-hydroxy-DHEA and 7-oxo-DHEA and test them in liquid chromatography-tandem mass spectrometry (LC-MS/MS) in order to enhance the performance characteristics of this method. Here we report the synthesis of 3alpha deuterium-labelled 7alpha-hydroxy-DHEA and 7-oxo-DHEA. Deuterium was introduced into the 3alpha position by reduction of the corresponding 3-ketone with a protected 17-carbonyl group using NaBD4. Our new procedure allows the easier synthesis of deuterated steroid labelled compounds. The use of these deuterated steroids enabled us to improve the human plasma LC MS/MS analysis of 7alpha-hydroxy-DHEA and 7-oxo-DHEA in terms of sensitivity, precision and recovery. PMID- 27192429 TI - Lacking of estradiol reduces insulin exocytosis from pancreatic beta-cells and increases hepatic insulin degradation. AB - Low levels of plasma estrogens are associated with weight-gain, android fat distribution, and a high prevalence of obesity-related comorbidities such as glucose intolerance and type II diabetes. The mechanisms underlying the association between low levels of estrogens and impaired glucose homeostasis are not completely understood. To begin to test this, we used three-month-old female C57BL/6J mice that either underwent ovariectomy (OVX) or received a sham surgery (Sham), and we characterized glucose homeostasis. In a subsequent series of experiments, OVX mice received estradiol treatment (OVX+E2) or vehicle (OVX) for 6 consecutive days. As has been previously reported, lack of ovarian hormones resulted in dysregulated glucose homeostasis. To begin to explore the mechanisms by which this occurs, we characterized the impact of estrogens on insulin secretion and degradation in these mice. Insulin secretion and plasma insulin levels were lower in OVX mice. OVX mice had lower levels of pancreatic Syntaxin 1 A (Synt-1A) protein, which is involved in insulin extrusion from the pancreas. In the liver, OVX mice had higher levels of insulin-degrading enzyme (IDE) and this was associated with higher insulin clearance. Estradiol treatment improved glucose intolerance in OVX mice and restored insulin secretion, as well as normalized the protein content of pancreatic Synt-1A. The addition of estrogens to OVX mice reduced IDE protein to that of Sham mice. Our data suggest loss of ovarian estradiol following OVX led to impaired glucose homeostasis due to pancreatic beta-cell dysfunction in the exocytosis of insulin, and upregulation of hepatic IDE protein content resulting in lower insulinemia, which was normalized by estradiol replacement. PMID- 27192428 TI - There goes the neighborhood: Assembly of transcriptional complexes during the regulation of metabolism and inflammation by the glucocorticoid receptor. AB - Glucocorticoids (GCs), as ligands for the glucocorticoid receptor (GR), represent one of the most effective and frequently used classes of drugs for anti inflammatory and immunosuppressive therapy. In addition, its role in physiological and pathophysiological processes makes the GR an important research target. The past decades have yielded a wealth of insight into the physiological and pharmacological effects of GCs. Today's era of next generation sequencing techniques is now beginning to elucidate the molecular and genomic circuits underlying GR's cell type-specific actions. This review focuses on the concepts and insights gained from recent studies in two of the most important tissues for GC action: the liver (mediating GR's metabolic effects) and macrophages (as the main target of anti-inflammatory GC therapy). We summarize results obtained from transgenic mouse models, molecular and genome-wide studies to illustrate GR's complex interactions with DNA, chromatin, co-regulators and other transcription factors. Characterizing the cell type-specific transcriptional complexes assembled around GR will pave the road for the development of new anti inflammatory and metabolic therapies in the future. PMID- 27192430 TI - Co-Prescription of QT-Interval Prolonging Drugs: An Analysis in a Large Cohort of Geriatric Patients. AB - BACKGROUND: Drug-induced QT-interval prolongation is associated with occurrence of potentially fatal Torsades de Pointes arrhythmias (TdP). So far, data regarding the overall burden of QT-interval prolonging drugs (QT-drugs) in geriatric patients are limited. OBJECTIVE: This study was performed to assess the individual burden of QT-interval prolonging drugs (QT-drugs) in geriatric polymedicated patients and to identify the most frequent and risky combinations of QT-drugs. METHODS: In the discharge medication of geriatric patients between July 2009 and June 2013 from the Geriatrics in Bavaria-Database (GiB-DAT) (co) prescriptions of QT-drugs were investigated. QT-drugs were classified according to a publicly available reference site (CredibleMeds(r)) as ALL-QT-drugs (associated with any QT-risk) or High-risk-QT-drugs (corresponding to QT-drugs with known risk of Torsades de Pointes according to CredibleMeds(r)) and in addition as SmPC-high-risk-QT-drugs (according to the German prescribing information (SmPC) contraindicated co-prescription with other QT-drugs). RESULTS: Of a cohort of 130,434 geriatric patients (mean age 81 years, 67% women), prescribed a median of 8 drugs, 76,594 patients (58.7%) received at least one ALL QT-drug. Co-prescriptions of two or more ALL-QT-drugs were observed in 28,768 (22.1%) patients. Particularly risky co-prescriptions of High-risk-QT-drugs or SmPC-high-risk-QT-drugs with at least on further QT-drug occurred in 55.9% (N = 12,633) and 54.2% (N = 12,429) of these patients, respectively. Consideration of SmPCs (SmPC-high-risk-QT-drugs) allowed the identification of an additional 15% (N = 3,999) patients taking a risky combination that was not covered by the commonly used CredibleMeds(r) classification. Only 20 drug-drug combinations accounted for more than 90% of these potentially most dangerous co-prescriptions. CONCLUSION: In a geriatric study population co-prescriptions of two and more QT drugs were common. A considerable proportion of QT-drugs with higher risk only could be detected by using more than one classification-system. Local adaption of international classifications can improve identification of patients at risk. PMID- 27192431 TI - Riparian shading controls instream spring phytoplankton and benthic algal growth. AB - Dissolved oxygen (DO) concentrations showed a striking pattern in a multi-year study of the River Enborne, a small river in SE England. In each of three years (2010-2012), maximum DO concentrations were attained in mid-April, preceded by a period of steadily increasing diurnal amplitudes, followed by a steady reduction in both amplitude and concentration. Flow events during the reduction period reduce DO to low concentrations until the following spring. Evidence is presented that this pattern is mainly due to benthic algal growth which is eventually suppressed by the growth of the riparian tree canopy. Nitrate and silicate concentrations are too high to inhibit the growth of either benthic algae or phytoplankton, but phosphate concentrations might have started to reduce growth if the tree canopy development had been delayed. This interpretation is supported by evidence from weekly flow cytometry measurements and analysis of the diurnal, seasonal and annual patterns of nutrient concentrations. As the tree canopy develops, the river switches from an autotrophic to a heterotrophic state. The results support the use of riparian shading to help control algal growth, and highlight the risks of reducing riparian shade. PMID- 27192433 TI - A Twin Protection Effect? Explaining Twin Survival Advantages with a Two-Process Mortality Model. AB - Twin studies that focus on the correlation in age-at-death between twin pairs have yielded important insights into the heritability and role of genetic factors in determining lifespan, but less attention is paid to the biological and social role of zygosity itself in determining survival across the entire life course. Using data from the Danish Twin Registry and the Human Mortality Database, we show that monozygotic twins have greater cumulative survival proportions at nearly every age compared to dizygotic twins and the Danish general population. We examine this survival advantage by fitting these data with a two-process mortality model that partitions survivorship patterns into extrinsic and intrinsic mortality processes roughly corresponding to acute, environmental and chronic, biological origins. We find intrinsic processes confer a survival advantage at older ages for males, while at younger ages, all monozygotic twins show a health protection effect against extrinsic death akin to a marriage protection effect. While existing research suggests an increasingly important role for genetic factors at very advanced ages, we conclude that the social closeness of monozygotic twins is a plausible driver of the survival advantage at ages <65. PMID- 27192432 TI - Genetic Deletion of the Clathrin Adaptor GGA3 Reduces Anxiety and Alters GABAergic Transmission. AB - Golgi-localized gamma-ear-containing ARF binding protein 3 (GGA3) is a monomeric clathrin adaptor that has been shown to regulate the trafficking of the Beta-site APP-cleaving enzyme (BACE1), which is required for production of the Alzheimer's disease (AD)-associated amyloid betapeptide. Our previous studies have shown that BACE1 is degraded via the lysosomal pathway and that depletion of GGA3 results in increased BACE1 levels and activity owing to impaired lysosomal trafficking and degradation. We further demonstrated the role of GGA3 in the regulation of BACE1 in vivo by showing that BACE1 levels are increased in the brain of GGA3 null mice. We report here that GGA3 deletion results in novelty-induced hyperactivity and decreased anxiety-like behaviors. Given the pivotal role of GABAergic transmission in the regulation of anxiety-like behaviors, we performed electrophysiological recordings in hippocampal slices and found increased phasic and decreased tonic inhibition in the dentate gyrus granule cells (DGGC). Moreover, we found that the number of inhibitory synapses is increased in the dentate gyrus of GGA3 null mice in further support of the electrophysiological data. Thus, the increased GABAergic transmission is a leading candidate mechanism underlying the reduced anxiety-like behaviors observed in GGA3 null mice. All together these findings suggest that GGA3 plays a key role in GABAergic transmission. Since BACE1 levels are elevated in the brain of GGA3 null mice, it is possible that at least some of these phenotypes are a consequence of increased processing of BACE1 substrates. PMID- 27192434 TI - Podocyte Depletion in Thin GBM and Alport Syndrome. AB - The proximate genetic cause of both Thin GBM and Alport Syndrome (AS) is abnormal alpha3, 4 and 5 collagen IV chains resulting in abnormal glomerular basement membrane (GBM) structure/function. We previously reported that podocyte detachment rate measured in urine is increased in AS, suggesting that podocyte depletion could play a role in causing progressive loss of kidney function. To test this hypothesis podometric parameters were measured in 26 kidney biopsies from 21 patients aged 2-17 years with a clinic-pathologic diagnosis including both classic Alport Syndrome with thin and thick GBM segments and lamellated lamina densa [n = 15] and Thin GBM cases [n = 6]. Protocol biopsies from deceased donor kidneys were used as age-matched controls. Podocyte depletion was present in AS biopsies prior to detectable histologic abnormalities. No abnormality was detected by light microscopy at <30% podocyte depletion, minor pathologic changes (mesangial expansion and adhesions to Bowman's capsule) were present at 30-50% podocyte depletion, and FSGS was progressively present above 50% podocyte depletion. eGFR did not change measurably until >70% podocyte depletion. Low level proteinuria was an early event at about 25% podocyte depletion and increased in proportion to podocyte depletion. These quantitative data parallel those from model systems where podocyte depletion is the causative event. This result supports a hypothesis that in AS podocyte adherence to the GBM is defective resulting in accelerated podocyte detachment causing progressive podocyte depletion leading to FSGS-like pathologic changes and eventual End Stage Kidney Disease. Early intervention to reduce podocyte depletion is projected to prolong kidney survival in AS. PMID- 27192436 TI - Porous Au-Ag Nanospheres with High-Density and Highly Accessible Hotspots for SERS Analysis. AB - Colloidal plasmonic metal nanoparticles have enabled surface-enhanced Raman scattering (SERS) for a variety of analytical applications. While great efforts have been made to create hotspots for amplifying Raman signals, it remains a great challenge to ensure their high density and accessibility for improved sensitivity of the analysis. Here we report a dealloying process for the fabrication of porous Au-Ag alloy nanoparticles containing abundant inherent hotspots, which were encased in ultrathin hollow silica shells so that the need of conventional organic capping ligands for stabilization is eliminated, producing colloidal plasmonic nanoparticles with clean surface and thus high accessibility of the hotspots. As a result, these novel nanostructures show excellent SERS activity with an enhancement factor of ~1.3 * 10(7) on a single particle basis (off-resonant condition), promising high applicability in many SERS-based analytical and biomedical applications. PMID- 27192437 TI - Group-wise parcellation of the cortex through multi-scale spectral clustering. AB - The delineation of functionally and structurally distinct regions as well as their connectivity can provide key knowledge towards understanding the brain's behaviour and function. Cytoarchitecture has long been the gold standard for such parcellation tasks, but has poor scalability and cannot be mapped in vivo. Functional and diffusion magnetic resonance imaging allow in vivo mapping of brain's connectivity and the parcellation of the brain based on local connectivity information. Several methods have been developed for single subject connectivity driven parcellation, but very few have tackled the task of group wise parcellation, which is essential for uncovering group specific behaviours. In this paper, we propose a group-wise connectivity-driven parcellation method based on spectral clustering that captures local connectivity information at multiple scales and directly enforces correspondences between subjects. The method is applied to diffusion Magnetic Resonance Imaging driven parcellation on two independent groups of 50 subjects from the Human Connectome Project. Promising quantitative and qualitative results in terms of information loss, modality comparisons, group consistency and inter-group similarities demonstrate the potential of the method. PMID- 27192439 TI - Investigating motivating factors for sound hospital waste management. AB - Sustainable management of hospital waste requires an active involvement of all key players. This study aims to test the hypothesis that three motivating factors, namely, Reputation, Liability, and Expense, influence hospital waste management. The survey for this study was conducted in two phases, with the pilot study used for exploratory factor analysis and the subsequent main survey used for cross-validation using confirmatory factor analysis. The hypotheses were validated through one-sample t tests. Correlations were established between the three motivating factors and organizational characteristics of hospital type, location, category, and size. The hypotheses were validated, and it was found that the factors of Liability and Expense varied considerably with respect to location and size of a hospital. The factor of Reputation, however, did not exhibit significant variation. In conclusion, concerns about the reputation of a facility and an apprehension of liability act as incentives for sound hospital waste management, whereas concerns about financial costs and perceived overburden on staff act as disincentives. IMPLICATIONS: This paper identifies the non economic motivating factors that can be used to encourage behavioral changes regarding waste management at hospitals in resource constrained environments. This study discovered that organizational characteristics such as hospital size and location cause the responses to vary among the subjects. Hence a policy maker must take into account the institutional setting before introducing a change geared towards better waste management outcomes across hospitals. This study covers a topic that has hitherto been neglected in resource constrained countries. Thus it can be used as one of the first steps to highlight and tackle the issue. PMID- 27192438 TI - Remission of Severe Opioid Use Disorder with Ibogaine: A Case Report. AB - BACKGROUND: Opioid use disorders (OUD) translate into major health, social, and economic consequences. Opioid agonist medications, which generally require long term administration, are the mainstay pharmacological treatment of OUD. However, a large proportion of individuals with OUD either refuse or fail to respond to these therapies. Ibogaine, a naturally occurring substance found in the Tabernanthe iboga plant, has shown potential to bring about transformative or spiritual experiences that have reportedly been associated with long-term abstinece. Although research on ibogaine is limited, an ibogaine subculture persists, offering unregulated ibogaine preparations for the treatment of addiction. CASE PRESENTATION: We describe the case of a 37-year-old female with a 19-year history of severe OUD achieving an ongoing 18-month period of abstinence following a four-day ibogaine treatment. Her previous longest period of continuous abstinence from opioids was two months while on methadone. No safety issues associated with ibogaine were observed. CONCLUSIONS: A four-day treatment with ibogaine was succesful in achieving long-term remission of a previously treatment-refractory patient with severe OUD. While rigorous trials are required to establish safety and efficacy, future studies should seek to delineate the potential role of ibogaine or other molecules that may produce transformative experiences for individuals with substance use disorder. PMID- 27192435 TI - Wnt Signaling Alteration in the Spinal Cord of Amyotrophic Lateral Sclerosis Transgenic Mice: Special Focus on Frizzled-5 Cellular Expression Pattern. AB - BACKGROUND: Amyotrophic lateral sclerosis is a chronic neurodegenerative disease characterized by progressive paralysis due to degeneration of motor neurons by unknown causes. Recent evidence shows that Wnt signaling is involved in neurodegenerative processes, including Amyotrophic Lateral Sclerosis. However, to date, little is known regarding the expression of Wnt signaling components in this fatal condition. In the present study we used transgenic SOD1G93A mice to evaluate the expression of several Wnt signaling components, with special focus on Frizzled-5 cellular expression alteration along disease progression. FINDINGS: Based on previous studies demonstrating the expression of Wnts and their transcriptional regulation during Amyotrophic lateral sclerosis development, we have analyzed the mRNA expression of several Wnt signaling components in the spinal cord of SOD1G93A transgenic mice at different stages of the disease by using real time quantitative PCR analysis. Strikingly, one of the molecules that seemed not to be altered at mRNA level, Frizzled-5, showed a clear up-regulation at late stages in neurons, as evidenced by immunofluorescence assays. Moreover, increased Frizzled-5 appears to correlate with a decrease in NeuN signal in these cells, suggesting a correlation between neuronal affectation and the increased expression of this receptor. CONCLUSIONS: Our data suggest the involvement of Wnt signaling pathways in the pathophysiology of Amyotrophic Lateral Sclerosis and, more specifically, the implication of Frizzled-5 receptor in the response of neuronal cells against neurodegeneration. Nevertheless, further experimental studies are needed to shed light on the specific role of Frizzled-5 and the emerging but increasing Wnt family of proteins research field as a potential target for this neuropathology. PMID- 27192440 TI - Efficient production of Aschersonia placenta protoplasts for transformation using optimization algorithms. AB - The insect pathogenic fungus Aschersonia placenta is a highly effective pathogen of whiteflies and scale insects. However, few genetic tools are currently available for studying this organism. Here we report on the conditions for the production of transformable A. placenta protoplasts using an optimized protocol based on the response surface method (RSM). Critical parameters for protoplast production were modelled by using a Box-Behnken design (BBD) involving 3 levels of 3 variables that was subsequently tested to verify its ability to predict protoplast production (R(2) = 0.9465). The optimized conditions resulted in the highest yield of protoplasts ((4.41 +/- 0.02) * 10(7) cells/mL of culture, mean +/- SE) when fungal cells were treated with 26.1 mg/mL of lywallzyme for 4 h of digestion, and subsequently allowed to recover for 64.6 h in 0.7 mol/L NaCl-Tris buffer. The latter was used as an osmotic stabilizer. The yield of protoplasts was approximately 10-fold higher than that of the nonoptimized conditions. Generated protoplasts were transformed with vector PbarGPE containing the bar gene as the selection marker. Transformation efficiency was 300 colonies/(MUg DNA.10(7) protoplasts), and integration of the vector DNA was confirmed by PCR. The results show that rational design strategies (RSM and BBD methods) are useful to increase the production of fungal protoplasts for a variety of downstream applications. PMID- 27192442 TI - Laboratory course on Streptomyces genetics and secondary metabolism. AB - The "Streptomyces genetics and secondary metabolism" laboratory course gives an introduction to the versatile soil dwelling Gram-positive bacteria Streptomyces and their secondary metabolism. The course combines genetic modification of Streptomyces; growing of the strain and protoplast preparation, plasmid isolation by alkaline lysis and phenol precipitation, digestions, and ligations prior to protoplast transformation, as well as investigating the secondary metabolites produced by the strains. Thus, the course is a combination of microbiology, molecular biology, and chemistry. After the course the students should understand the relationship between genes, proteins, and the produced metabolites. (c) 2016 by The International Union of Biochemistry and Molecular Biology, 44(5):492-499, 2016. PMID- 27192443 TI - Gay Men and Lesbian Women Who Become Parents in the Context of a Former Heterosexual Relationship: An Explorative Study in Italy. AB - In Italy, homosexual people are not allowed to perform donor insemination/surrogacy or adoption, thus they become parents mainly in the context of previous heterosexual relationships. The current study examines the experiences of 34 gay fathers and 32 lesbian mothers with children from a heterosexual relationship. Data on homosexuality awareness, reasons for marriage and parenthood, and the coming-out process to children were collected. Most participants reported not being aware of their homosexuality when they married and became parents. The most common reasons for marriage were "love" and "social expectancy," whereas parenthood was motivated mainly by the "desire for children and family." Most participants came out to at least one child and reported a positive reaction. The most cited benefit of coming out was "openness/not hiding anymore." The results suggest that the lives of gay and lesbian parents are shaped by their sexual minority status as well as by societal heterosexism. PMID- 27192441 TI - Release of GTP Exchange Factor Mediated Down-Regulation of Abscisic Acid Signal Transduction through ABA-Induced Rapid Degradation of RopGEFs. AB - The phytohormone abscisic acid (ABA) is critical to plant development and stress responses. Abiotic stress triggers an ABA signal transduction cascade, which is comprised of the core components PYL/RCAR ABA receptors, PP2C-type protein phosphatases, and protein kinases. Small GTPases of the ROP/RAC family act as negative regulators of ABA signal transduction. However, the mechanisms by which ABA controls the behavior of ROP/RACs have remained unclear. Here, we show that an Arabidopsis guanine nucleotide exchange factor protein RopGEF1 is rapidly sequestered to intracellular particles in response to ABA. GFP-RopGEF1 is sequestered via the endosome-prevacuolar compartment pathway and is degraded. RopGEF1 directly interacts with several clade A PP2C protein phosphatases, including ABI1. Interestingly, RopGEF1 undergoes constitutive degradation in pp2c quadruple abi1/abi2/hab1/pp2ca mutant plants, revealing that active PP2C protein phosphatases protect and stabilize RopGEF1 from ABA-mediated degradation. Interestingly, ABA-mediated degradation of RopGEF1 also plays an important role in ABA-mediated inhibition of lateral root growth. The presented findings point to a PP2C-RopGEF-ROP/RAC control loop model that is proposed to aid in shutting off ABA signal transduction, to counteract leaky ABA signal transduction caused by "monomeric" PYL/RCAR ABA receptors in the absence of stress, and facilitate signaling in response to ABA. PMID- 27192444 TI - Loss of 89K Pathogenicity Island in Epidemic Streptococcus suis, China. PMID- 27192445 TI - Elucidating Quantum Confinement in Graphene Oxide Dots Based On Excitation Wavelength-Independent Photoluminescence. AB - Investigating quantum confinement in graphene under ambient conditions remains a challenge. In this study, we present graphene oxide quantum dots (GOQDs) that show excitation-wavelength-independent photoluminescence. The luminescence color varies from orange-red to blue as the GOQD size is reduced from 8 to 1 nm. The photoluminescence of each GOQD specimen is associated with electron transitions from the antibonding pi (pi*) to oxygen nonbonding (n-state) orbitals. The observed quantum confinement is ascribed to a size change in the sp(2) domains, which leads to a change in the pi*-pi gap; the n-state levels remain unaffected by the size change. The electronic properties and mechanisms involved in quantum confined photoluminescence can serve as the foundation for the application of oxygenated graphene in electronics, photonics, and biology. PMID- 27192446 TI - Not What the Textbooks Describe: Challenging Clinical Conventions About Psychosis. PMID- 27192447 TI - SnAP-eX Reagents for the Synthesis of Exocyclic 3-Amino- and 3-Alkoxypyrrolidines and Piperidines from Aldehydes. AB - SnAP-eX (tin amine protocol, exocyclic heteroatoms) reagents allow the single step transformation of aldehydes and ketones into 2,3-disubstituted pyrrolidines and piperidines containing exocyclic amine or alkoxy groups. These saturated N heterocycles are of importance in modern drug discovery approaches and are prepared in moderate yields using an operationally simple protocol that is compatible with a range of functional groups and heterocyclic aldehydes. PMID- 27192451 TI - Doctor to Doctor. PMID- 27192452 TI - Conference Call. PMID- 27192449 TI - RESAMA: A Network for Monitoring Health and Husbandry Practices in Aquatic Research Facilities. AB - Health monitoring is a crucial aspect of the management of any research animal house. RESAMA is a network strong of 60 academic and private partners acting in France since the end of 2012. The network aims to increase awareness of animal caretakers and researchers on health management issues in facilities holding aquatic model species (zebrafish, Xenopus, medaka, Mexican tetra). To do so, each partner research facility will be visited at least once. The visiting team is composed at least of one veterinarian and one zootechnician specialized in aquatic species. The visit results in a health-monitoring assessment of the facility, which includes a sampling for histo-pathological, bacteriological, and molecular pathogen detection. During the visit, rearing practices are also reviewed through an interview of animal caretakers. However, the present report essentially focuses on the health-monitoring aspect. The ultimate goal of the project is to provide a network-wide picture of health issues in aquatic facilities. Performed in parallel, the rearing practice assessment will ultimately help to establish rational relationship between handling practices and animal health in aquatic facilities. The study is still in progress. Here, we describe the results to be drawn from an analysis of the 23 facilities that had been visited so far. We sampled 720 fish and 127 amphibians and performed a little less than 1400 individual tests. PMID- 27192448 TI - Controlled Sculpture of Black Phosphorus Nanoribbons. AB - Black phosphorus (BP) is a highly anisotropic allotrope of phosphorus with great promise for fast functional electronics and optoelectronics. We demonstrate the controlled structural modification of few-layer BP along arbitrary crystal directions with sub-nanometer precision for the formation of few-nanometer-wide armchair and zigzag BP nanoribbons. Nanoribbons are fabricated, along with nanopores and nanogaps, using a combination of mechanical-liquid exfoliation and in situ transmission electron microscopy (TEM) and scanning TEM nanosculpting. We predict that the few-nanometer-wide BP nanoribbons realized experimentally possess clear one-dimensional quantum confinement, even when the systems are made up of a few layers. The demonstration of this procedure is key for the development of BP-based electronics, optoelectronics, thermoelectrics, and other applications in reduced dimensions. PMID- 27192454 TI - Literature Scan. PMID- 27192453 TI - Pearls. PMID- 27192455 TI - cme credit Quiz. PMID- 27192457 TI - Combating acne. PMID- 27192458 TI - "Chasing a Ghost": Factors that Influence Primary Care Physicians to Follow Up on Incidental Imaging Findings. AB - Purpose To explore provider and patient characteristics that influence how primary care providers (PCPs) communicate and manage incidental imaging findings. Materials and Methods This HIPAA-compliant study was approved by the institutional review board. Through semistructured interviews, researchers explored concerns and perspectives of 30 PCPs on receiving and acting on incidental imaging findings. Open-ended questions were designed to elicit a range of responses rather than quantifiable data. Thematic codes were developed and explicitly defined. Three research assistants independently coded all 30 deidentified transcripts and resolved discrepancies (kappa = 0.85). Codes pertaining to PCP and patient characteristics were organized into an explanatory model. Results Some PCPs felt compelled but frustrated to pursue costly follow-up for incidental imaging findings of limited clinical importance. Other PCPs did not act on findings that were unfamiliar or occurred in an unusual clinical context when follow-up recommendations were not given; the challenges of researching the clinical importance of these findings or seeking specialist consultation led to inaction. Some PCPs reported using a uniform approach to communicate and manage incidental findings, while others adapted their approach to the patient and the finding. Sometimes PCP characteristics such as follow-up style superseded patient characteristics. At other times patient characteristics such as health literacy superseded PCP characteristics. Conclusion PCPs cited a variety of objective and subjective factors that influence how they communicate and manage incidental imaging findings. These results suggest that some patients may receive inappropriate follow-up of incidental imaging findings and present an opportunity for radiologists to help PCPs and patients to best use the information conveyed in imaging reports. (c) RSNA, 2016 Online supplemental material is available for this article. PMID- 27192459 TI - Focused Ultrasound Enhances Central Nervous System Delivery of Bevacizumab for Malignant Glioma Treatment. AB - Purpose To demonstrate that magnetic resonance (MR) imaging-monitored transcranial focused ultrasound can enhance the delivery of the antiangiogenic monoclonal antibody bevacizumab into the central nervous system (CNS) for glioblastoma multiforme (GBM) treatment. Materials and Methods All animal experiments were approved by the animal committee and adhered to experimental animal care guidelines. Transcranial focused ultrasound exposure in the presence of microbubbles was used to open the blood-brain barrier (BBB) to enhance bevacizumab penetration into the CNS in healthy and glioma-bearing mice. Bevacizumab concentration was quantitated with high-performance liquid chromatography, and Western blot testing was performed to confirm the specific biologic form in the CNS. Penetration of bevacizumab into brain tissue was estimated in vivo by means of contrast material-enhanced MR imaging and quantitative gallium 68 ((68)Ga)-bevacizumab micro-positron emission tomography, and glioma progression was longitudinally followed with T2-weighted MR imaging. Hematoxylin-eosin staining and cluster of differentiation 31 immunostaining were used to assess morphologic changes and vascular inhibition at histologic examination. The two-tailed Student t test and the Mantel-Cox log-rank test were used for statistical analyses, with a significance level of .05. Results Focused ultrasound significantly enhanced bevacizumab penetration into the CNS by 5.7- to 56.7-fold compared with that in nonexposed brain (both P < .0001). Contrast enhanced MR imaging indexes correlated with bevacizumab concentration (r = 0.748 0.857) in vivo. Focused ultrasound-enhanced bevacizumab delivery significantly retarded glioma progression, with a significantly increased median survival (median increase in survival time = 135% in the group treated with bevacizumab and focused ultrasound, P < .0001; as compared with 48% in the group treated with bevacizumab alone, P = .0002). Conclusion Focused ultrasound-enhanced bevacizumab delivery can provide an antivascularization normalization effect to suppress glioma. ((c)) RSNA, 2016 Online supplemental material is available for this article. PMID- 27192460 TI - Time-Intensity Curves Obtained after Microbubble Injection Can Be Used to Differentiate Responders from Nonresponders among Patients with Clinically Active Crohn Disease after 6 Weeks of Pharmacologic Treatment. AB - Purpose To assess whether contrast material-enhanced ultrasonography (US) can be used to differentiate responders from nonresponders among patients with clinically active Crohn disease after 6 weeks of pharmacologic treatment. Materials and Methods This prospective study was approved by our ethics committee, and written informed consent was obtained from all patients. Fifty consecutive patients (26 men and 24 women; mean age, 34.76 years +/- 9) with a proved diagnosis of active Crohn disease who were scheduled to begin therapy with biologics (infliximab or adalimumab) were included, with enrollment from June 1, 2013, to June 1, 2015. In each patient, the terminal ileal loop was imaged with contrast-enhanced US before the beginning and at the end of week 6 of pharmacologic treatment. Time-intensity curves obtained in responders (those with a decrease in the Crohn disease endoscopic index of severity score of 25-44 before treatment to 10-15 after treatment, an inflammatory score <7, and/or a decrease >=70 in the Crohn disease activity index score compared with baseline) and nonresponders were compared with Mann-Whitney test. Results Responders (n = 31) and nonresponders (n = 19) differed (P < .05) in the percent change of peak enhancement (-40.78 +/- 62.85 vs 53.21 +/- 72.5; P = .0001), wash-in (-34.8 +/- 67.72 vs 89.44 +/- 145.32; P = .001) and washout (-5.64 +/- 130.71 vs 166.83 +/- 204.44; P = .002) rate, wash-in perfusion index (-42.29 +/- 59.21 vs 50.96 +/- 71.13; P = .001), area under the time-intensity curve (AUC; -46.17 +/- 48.42 vs 41.78 +/- 87.64; P = .001), AUC during wash-in (-43.93 +/- 54.29 vs 39.79 +/- 70.85; P = .001), and AUC during washout (-49.36 +/- 47.42 vs 42.65 +/- 97.09; P = .001). Responders and nonresponders did not differ in the percent change of rise time (5.09 +/- 49.13 vs 6.24 +/- 48.06; P = .93) and time to peak enhancement (8.82 +/- 54.5 vs 10.21 +/- 43.25; P = .3). Conclusion Analysis of time-intensity curves obtained after injection of microbubble contrast material 6 weeks after beginning pharmacologic treatment can be used to differentiate responders from nonresponders among patients with clinically active Crohn disease. (c) RSNA, 2016. PMID- 27192461 TI - Diagnostic Performance of Self-navigated Whole-Heart Contrast-enhanced Coronary 3 T MR Angiography. AB - Purpose To evaluate the diagnostic performance of self-navigated whole-heart coronary 3-T magnetic resonance (MR) angiography by using conventional invasive coronary angiography (ICA) as the reference gold standard. Materials and Methods This study was approved by the local ethics committee. Written informed consent was obtained from each patient before the study. Thirty-nine consecutive patients underwent coronary MR angiography and later underwent ICA. Coronary MR angiography was performed with a 3-T imager with contrast agent enhancement during free breathing with self-navigated affine motion correction reconstruction. Coronary segments with reference diameters larger than 1.5 mm were included in the comparison between coronary MR angiography and ICA. The coronary MR angiography images were evaluated by two experienced readers blinded to the ICA results to identify significant luminal narrowing (>50% diameter reduction in reference ICA). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were performed to detect significant coronary artery stenosis. Results Coronary MR angiography examinations were successfully performed in all 39 patients. A total of 327 coronary segments had reference luminal diameter larger than 1.5 mm. Of these 327 coronary segments, 303 (92.7%) segments had a quality score greater than 1 at coronary MR angiography and were included in the analysis. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 78.2%, 75.0%, 81.8%, 70.6%, and 76.9%, respectively, on a per-patient basis. Conclusion Contrast-enhanced self-navigated coronary 3-T MR angiography is a promising technique for the noninvasive detection of clinically significant coronary stenosis. (c) RSNA, 2016. PMID- 27192463 TI - A case of trapped lung by a fractured rib. PMID- 27192464 TI - Managing missed lower extremity compartment syndrome in the physiologically stable patient: A systematic review and lessons from a Level I trauma center. AB - BACKGROUND: Decompressing an acute lower extremity compartment syndrome salvages muscle and nerve and preserves limb function. However, reperfusion of ischemic tissue causes a systemic insult that can be life threatening. Hence, the management of missed acute lower limb compartment syndrome remains controversial. The aim of this study was to evaluate the literature and, together with our own experience from a Level 1 trauma center, clarify the management of missed compartment syndrome in the physiologically stable patient. METHODS: Pubmed, EMBASE, MEDLINE, the Cochrane database of systematic reviews and the Cochrane central register of controlled trials were searched. Studies were evaluated using the GRADE methodology. In addition, our trauma database was searched (2005 to May 2015) for additional cases, and a multidisciplinary case note review was conducted for all cases identified. This study was registered prospectively on the PROSPERO database (CRD42015026098). RESULTS: Our systematic review yielded 9 studies, including one case-controlled study, 3 case series, and 5 case reports with a total of 57 patients and 64 limbs. Overall, study quality was "very low" with the exception of the case-controlled study, which was "low." Delayed compartment decompression (6-120 hours) resulted in amputation rates of 5 of 24, 8 of 19, 4 of 5, and 2 of 3 limbs. Two patients died of complications associated with late compartment decompression. One compartment syndrome of the buttock was managed nonoperatively. Most surviving limbs exhibited functional deficits.Additionally, our experience comprised 10 cases. Of the six who underwent compartment decompression, the burden of subsequent morbidity included three amputations (one above knee), two complete foot drops, and one episode of severe sepsis. As this experience mirrored the poor outcomes reported in the literature, we managed the four most recent cases nonoperatively. All remain ambulant with incomplete foot drops or limb weakness. CONCLUSION: Surgical decompression of missed acute lower limb compartment syndrome yields an early physiological insult and a high late-amputation rate. Managing selected cases nonoperatively may result in less early morbidity and yield superior long-term results, but the evidence remains sparse and of poor quality. LEVEL OF EVIDENCE: Systematic review, level III. PMID- 27192465 TI - Repainting the ceiling: Do patient safety and satisfaction initiatives make things safer or more satisfying? PMID- 27192466 TI - Emergent non-image-guided resuscitative endovascular balloon occlusion of the aorta (REBOA) catheter placement: A cadaver-based study. AB - BACKGROUND: Emergent resuscitative endovascular balloon occlusion of the aorta (REBOA) insertion for critically injured patients in hemorrhagic shock is performed blindly with fluoroscopic imaging confirmation. The aim of this study was to determine a reliable method for initial REBOA catheter insertion with balloon deployment between the left subclavian artery takeoff and the celiac trunk (CT). METHODS: Human cadaver study. External surface (sternal notch, mid sternum, xiphoid) and intravascular (left subclavian artery [LSA], and CT) landmarks were measured from standardized left and right common femoral artery puncture sites. The landing zone (LZ, distance between LSA and CT) and margins of safety (distance from distal balloon edge to LSA and proximal balloon edge to CT) were calculated using intravascular landmarks. The probability of balloon deployment in the LZ using external landmarks was compared in univariate analysis using the Fisher exact test. RESULTS: Ten cadavers were analyzed (seven males; mean body mass index, 19.4 kg/m). Mean (SD) intravascular distances from femoral puncture sites to the LSA and CT were 54.8 (1.9) cm and 32.9 (1.9) cm. The mean (SD) LZ was 21.8 (3.8) cm. Mean (SD) surface distances from femoral puncture sites to the xiphoid, mid-sternum, and sternal notch were 31.8 (3.9) cm, 41.8 (3.3) cm, and 51.8 (3.2) cm. Inserting the catheter to a distance approximated by surface distance from the femoral puncture site to mid-sternum resulted in a 100% likelihood balloon deployment in the LZ for both sides. This was superior to the xiphoid and sternal notch (left site, p = 0.005; right site, p = 0.036; mean of both sites, p = 0.083). Using the mid-sternum landmark, the mean (SD) margins of safety to the LSA and CT were 10.7 (4.3) cm and 3.1 (3.4) cm. CONCLUSION: When using the use of the mid-sternum landmark for REBOA balloon placement, the likelihood of balloon deployment in the LZ was 100% with an acceptable margin of safety. PMID- 27192467 TI - Correlation between laboratory coagulation testing and thromboelastometry is modified during management of trauma patients. AB - BACKGROUND: Thromboelastometry (ROTEM, Pentapharm GmbH, Munich, Germany) is increasingly being used to make a diagnosis of coagulopathy and to guide hemostatic therapy (HT). Although ROTEM parameters and standard laboratory test (SLT) correlated well before administration of HT, it is not known if this correlation persists after hemostatic resuscitation. METHODS: A retrospective analysis of prospectively collected data from a trauma registry (2011-2014) was performed. All patients having a ROTEM analysis were included. ROTEM parameters (clotting time and clot amplitude at 5 minutes) were determined after activation with tissue factor (EXTEM) or platelet inhibition with cytochalasin D (FIBTEM). Spearman rank correlation coefficient was calculated for the correlation between SLT and thromboelastometry parameters, and thresholds were determined with receiver operating characteristic (ROC) curve analysis for the diagnosis of an international normalized ratio (INR) greater than 1.5, fibrinogen 1.5 g/L or less, and platelet count of less than 100.10/L. RESULTS: Of the 358 patients included, 533 thromboelastometry results were obtained (335 at admission, 198 during care). Correlation between INR and EXTEM-clotting time was good at admission (r = 0.617) in the whole cohort but decreased in the subgroup of patients having an Injury Severity Score of less than 25 (r = 0.399) or a base excess of less than 6 mmol/L (r = 0.489). During care, correlation was impaired after the administration of fibrinogen concentrates in the whole cohort (r = 0.430), as well as in the subgroup of patients having an Injury Severity Score greater than 24 (r = 0.465). As well, for the diagnosis of increased INR, sensitivity and the area under the ROC curve decreased from 75% and 0.894 (no treatment) to 20% and 0.653 (fibrinogen concentrate). Areas under the ROC curve for the prediction of a fibrinogen or platelet decrease were not significantly altered regardless of the treatment group. CONCLUSIONS: A decrease in the correlation between SLTs and ROTEM parameters was observed at admission or during care, which could be in relation with injury severity, base deficit, or the administration of blood products, particularly fibrinogen concentrate. Further work will be necessary to better understand which tool is the most suitable for guiding HT. LEVEL OF EVIDENCE: Therapeutic study, level IV; diagnostic study, level IV. PMID- 27192468 TI - Delayed presentation of pulmonary hernia following surgical stabilization of severe rib fractures. PMID- 27192470 TI - Contemporary management of civilian penetrating cervicothoracic arterial injuries. AB - BACKGROUND: The management of arterial injury at the thoracic outlet has long hinged on the fundamental principles of extensile exposure and vascular anastomosis. Nonetheless, treatment options for such injuries have evolved to include both endovascular stent placement and temporary vascular shunts. The purpose of this study was to evaluate our recent experience with penetrating cervicothoracic arterial injuries in light of these developments in trauma care. METHODS: Patients with penetrating injuries to the innominate, carotid, subclavian, or axillary arteries managed at a single civilian trauma center between 2000 and 2013 were categorized as the modern era (ME) cohort. The management strategies and outcomes pertaining to the ME group were compared to those of previously reported experience (PE) concerning injuries to the innominate, carotid, subclavian, or axillary arteries at the same institution from 1974 to 1988. RESULTS: Over the two eras, there were 202 patients: 110 in the ME group and 92 in the PE group. Most of the injuries in both groups were managed with primary repair (45% vs. 46%; p = 0.89). A similar proportion of injuries in each group was managed with anticoagulation alone (14% vs. 10%; p = 0.40). In the ME group, two cases were managed with temporary shunt placement, and endovascular stent placement was performed in 12 patients. Outcomes were similar between the groups (bivariate comparison): mortality (ME, 15% vs. PE, 14%; p = 0.76), amputation following subclavian or axillary artery injury (ME, 5% vs. PE, 4%; p = 0.58), and posttreatment stroke following carotid injury (ME, 2% vs. PE, 6%; p = 0.57). CONCLUSIONS: Experience with penetrating arterial cervicothoracic injuries at a high-volume urban trauma center remained remarkably similar with respect to both anatomic distribution of injury and treatment. Conventional operative exposure and repair remain the cornerstone of treatment for most civilian cervicothoracic arterial injuries. LEVEL OF EVIDENCE: Therapeutic study, level V. PMID- 27192472 TI - Limiting chest computed tomography in the evaluation of pediatric thoracic trauma. AB - BACKGROUND: Computed tomography (CT) of the chest (chest CT) is overused in blunt pediatric thoracic trauma. Chest CT adds to the diagnosis of thoracic injury but rarely changes patient management. We sought to identify a subset of blunt pediatric trauma patients who would benefit from a screening chest CT based on their admission chest x-ray (CXR) findings. We hypothesize that limiting chest CT to patients with an abnormal mediastinal silhouette identifies intrathoracic vascular injuries not otherwise seen on CXR. METHODS: All blunt trauma activations that underwent an admission CXR at our Level 1 pediatric trauma center from 2005 to 2013 were retrospectively reviewed. Patients who had a chest CT were evaluated for added diagnoses and change in management after CT. RESULTS: An admission CXR was performed in 1,035 patients. One hundred thirty-nine patients had a CT, and the diagnosis of intra-thoracic injury was added in 42% of patients. Chest CT significantly increased the diagnosis of contusion or atelectasis (30.3% vs 60.4%; p < 0.05), pneumothorax (7.2% vs 18.7%; p < 0.05), and other fractures (4.3% vs 10.8%; p < 0.05) on CXR compared to chest CT. Chest CT changed the management of only 4 patients (2.9%). Two patients underwent further radiologic evaluation that was negative for injury, one had a chest tube placed for an occult pneumothorax before exploratory laparotomy, and one patient had a thoracotomy for repair of aortic injury. Chest CT for select patients with an abnormal mediastinal silhouette on CXR would have decreased CT scans by 80% yet still identified patients with an intrathoracic vascular injury. CONCLUSIONS: The use of chest CT should be limited to the identification of intrathoracic vascular injuries in the setting of an abnormal mediastinal silhouette on CXR. LEVEL OF EVIDENCE: Therapeutic study, level IV; diagnostic study, level III. PMID- 27192471 TI - Reducing acute kidney injury due to vancomycin in trauma patients. AB - BACKGROUND: Supratherapeutic vancomycin trough levels are common after trauma and associated with both increased acute kidney injury (AKI) and mortality. We sought to limit the adverse effects of vancomycin in trauma patients through more frequent trough monitoring. METHODS: Beginning in January 2011, trauma patients treated with vancomycin had trough levels (VT) monitored daily until steady state was reached. Trauma patients admitted from January 2011 to May 2015 (POST) were compared with those admitted from January 2006 to December 2010 (PRE). Inclusion criteria required administration of intravenous vancomycin, admission serum creatinine (SCr), and SCr within 72 hours of highest VT. Acute kidney injury was defined as an increase in SCr of at least 0.3 mg/dL or 50% from admission to post vancomycin administration. Those in the POST group were prospectively followed up until discharge or death. RESULTS: Two hundred sixty-three patients met inclusion criteria in the PRE-phase and 115 in the POST-phase. The two groups were similar in age, gender, race, body mass index, pre-existing comorbidities, admission systolic blood pressure, Glasgow Coma Scale, and head Abbreviated Injury Scale. Injury Severity Score was higher in the POST cohort (18 PRE vs. 25 POST, p < 0.001). Compared with PRE, the POST cohort had lower rates of supratherapeutic VT (>20 mg/L) (34.6% PRE vs. 22.6% POST, p = 0.02) and AKI (30.4% PRE vs. 19.1% POST, p = 0.026). After adjusting for confounders, the POST group had a significantly lower risk of AKI with an adjusted odds ratio of 0.457 (p = 0.027). There was a trend toward decreased mortality in the POST cohort, but this did not reach significance (10% PRE vs. 5.2% POST, p = 0.162). CONCLUSIONS: A reduction in AKI was observed in trauma patients with daily vancomycin trough levels monitored until steady state. Increased awareness regarding closer surveillance of VT in trauma patients may limit the incidence of vancomycin-related nephrotoxicity. LEVEL OF EVIDENCE: Therapeutic study, level IV. PMID- 27192473 TI - Smartkuber: A Serious Game for Cognitive Health Screening of Elderly Players. AB - OBJECTIVE: The goal of this study was to design and develop a serious game for cognitive health screening of the elderly, namely Smartkuber, and evaluate its construct, criteria (concurrent and predictive), and content validity, assessing its relationship with the Montreal Cognitive Assessment (MoCA) test. Furthermore, the study aims to evaluate the elderly players' game experience with Smartkuber. SUBJECTS AND METHODS: Thirteen older adults were enrolled in the study. The game was designed and developed by a multidisciplinary team. The study follows a mixed methodological approach, utilizing the In-Game Experience Questionnaire to assess the players' game experience and a correlational study, to examine the relationship between the Smartkuber and MoCA scores. The learning effect is also examined by comparing the mean game scores of the first and last game sessions of each player (Delta scores). RESULTS: All 13 participants (mean age: 68.69, SD: 7.24) successfully completed the study. Smartkuber demonstrated high concurrent validity with the MoCA test (r = 0.81, P = 0.001) and satisfying levels of predictive and content validity. The Delta scores showed no statistically significant differences in scoring, thus indicating no learning effects during the Smartkuber game sessions. CONCLUSIONS: The study shows that Smartkuber is a promising tool for cognitive health screening, providing an entertaining and motivating gaming experience to elderly players. Limitations of the study and future directions are discussed. PMID- 27192474 TI - The Enigma of Postoperative Troponin Elevation. PMID- 27192475 TI - Predicting the Best Fit: A Comparison of Response Surface Models for Midazolam and Alfentanil Sedation in Procedures With Varying Stimulation. AB - BACKGROUND: Selecting an effective dose of sedative drugs in combined upper and lower gastrointestinal endoscopy is complicated by varying degrees of pain stimulation. We tested the ability of 5 response surface models to predict depth of sedation after administration of midazolam and alfentanil in this complex model. The procedure was divided into 3 phases: esophagogastroduodenoscopy (EGD), colonoscopy, and the time interval between the 2 (intersession). METHODS: The depth of sedation in 33 adult patients was monitored by Observer Assessment of Alertness/Scores. A total of 218 combinations of midazolam and alfentanil effect site concentrations derived from pharmacokinetic models were used to test 5 response surface models in each of the 3 phases of endoscopy. Model fit was evaluated with objective function value, corrected Akaike Information Criterion (AICc), and Spearman ranked correlation. A model was arbitrarily defined as accurate if the predicted probability is <0.5 from the observed response. RESULTS: The effect-site concentrations tested ranged from 1 to 76 ng/mL and from 5 to 80 ng/mL for midazolam and alfentanil, respectively. Midazolam and alfentanil had synergistic effects in colonoscopy and EGD, but additivity was observed in the intersession group. Adequate prediction rates were 84% to 85% in the intersession group, 84% to 88% during colonoscopy, and 82% to 87% during EGD. The reduced Greco and Fixed alfentanil concentration required for 50% of the patients to achieve targeted response Hierarchy models performed better with comparable predictive strength. The reduced Greco model had the lowest AICc with strong correlation in all 3 phases of endoscopy. Dynamic, rather than fixed, gamma and gammaalf in the Hierarchy model improved model fit. CONCLUSIONS: The reduced Greco model had the lowest objective function value and AICc and thus the best fit. This model was reliable with acceptable predictive ability based on adequate clinical correlation. We suggest that this model has practical clinical value for patients undergoing procedures with varying degrees of stimulation. PMID- 27192476 TI - Hemostatic Therapy Using Tranexamic Acid and Coagulation Factor Concentrates in a Model of Traumatic Liver Injury. AB - BACKGROUND: The potential clinical benefits of targeted therapy with coagulation factor concentrates (e.g., fibrinogen) and antifibrinolytic agents (e.g., tranexamic acid [TXA]) for the treatment of trauma-induced coagulopathy are increasingly recognized. We hypothesized that human fibrinogen concentrate (FC) and prothrombin complex concentrate (PCC), administered as combined therapy with TXA, would provide additive effects for reducing blood loss in an animal trauma model. METHODS: Thirty-six pigs were subjected to 2 consecutive blunt liver injuries, resulting in severe hemorrhagic shock and coagulopathy. Intervention comprised saline (control group); TXA (15 mg kg, TXA group); TXA and FC (90 mg kg, TXA-FC); or TXA, FC, and PCC (20 U kg, TXA-FC-PCC). Blood loss, thromboelastometry (ROTEM), measures of thrombin generation, platelet activation, and global coagulation variables were monitored for 4 hours. Tissue sections were examined to determine the occurrence of thromboembolic events. RESULTS: Total blood loss was similar in the TXA-FC and TXA-FC-PCC groups (mean +/- SD: 1012 +/- 86 mL and 1037 +/- 118 mL, respectively; P = 1.000). These values were both lower (P < 0.001) than the TXA group (1579 +/- 306 mL). Blood loss in all 3 intervention groups was lower (P < 0.001) than in the control group (2376 +/- 478 mL). After trauma and resuscitation, but before study intervention, plasma fibrinogen levels were severely depleted (median for the whole study population: 66 mg dL; interquartile range: 51-108 mg dL) and clot strength was decreased (EXTEM whole-blood maximum clot firmness [MCF]: 53 +/- 5 mm). Compared with controls, TXA inhibited fibrinolysis and stabilized MCF and clotting time. The addition of FC restored and stabilized hemostasis to a greater extent than TXA alone; the addition of PCC had no statistically significant impact on blood loss, clot strength (MCF), or clotting time, but it increased thrombin generation. There were no significant differences among the study groups regarding platelet activation. No thrombi or microthrombi were observed in any group at necropsy. CONCLUSIONS: The early use of TXA and FC reduced blood loss and improved coagulation measurements in a porcine model of blunt liver injury and hemorrhagic shock. FC, administered in addition to TXA, was highly effective in reducing blood loss. The lack of statistically significant reduction in blood loss when PCC was added to TXA and FC may be attributable to the absence of thrombin generation impairment in this model. PMID- 27192477 TI - Ergonomic analysis of working postures using OWAS in semi-trailer assembly, applying an individual sampling strategy. AB - In semi-trailer assembly, workers are exposed to several physical risk factors. Awkward working postures have not yet been investigated in semi-trailer assembly, although they are known to be a major risk factor for musculoskeletal disorders. We therefore conducted a comprehensive ergonomic analysis of working postures using the Ovako working posture analysing system (OWAS), with an individual sampling strategy. The postural load in semi-trailer assembly was assessed on the basis of 20,601 observations of 63 workers executing a representative set of nine work tasks. According to the OWAS, the postural load of various working postures and body part positions may have a harmful effect on the musculoskeletal system. We therefore give examples of corrective measures that could improve awkward working postures. Applying an individual sampling strategy was revealed to have advantages over a collective strategy, so this is recommended for future ergonomic analyses. PMID- 27192478 TI - Can chlorination co-select antibiotic-resistance genes? AB - Selective pressures, such as chemical or heavy metal pollution, may co-select for bacterial antibiotic resistance in the environment. However, whether chlorination in water treatment can co-select antibiotic-resistant bacteria is controversial. In this study, high capacity quantitative polymerase chain reaction (qPCR) analysis was applied to target almost all known antibiotic-resistance genes (ARGs) (282 types) and 13 mobile genetic elements (MGEs) in bacteria detected in secondary effluents from a municipal wastewater treatment plant after chlorination. The results revealed that 125 unique ARGs were detected in non chlorinated samples, and the number decreased (79-91 types) as the chlorine concentration was increased. Moreover, 7.49 * 10(4)-3.92 * 10(7) copies/100 ml water reduction of ARGs occurred with 4 mg Cl2/l. Considering the relative abundance of ARGs (i.e., ARG copies normalized to 16S rRNA gene copies), 119 ARGs decreased in response to chlorination, whereas only six ARGs, such as dfrA1, tetPB-03, tetPA, ampC-04, tetA-02, and erm(36), were potentially enriched by 10.90-, 10.06-, 8.63-, 6.86-, 3.77-, and 1.09-fold, respectively. Furthermore, the relative abundance of 12 detected MGEs was lower after chlorination. Therefore, chlorination was effective in reducing ARGs and MGEs rather than co selecting them. PMID- 27192479 TI - Bioaccumulation of (63)Ni in the scleractinian coral Stylophora pistillata and isolated Symbiodinium using radiotracer techniques. AB - Development of nickel mining activities along the New Caledonia coasts threatens the biodiversity of coral reefs. Although the validation of tropical marine organisms as bioindicators of metal mining contamination has received much attention in the literature over the last decade, few studies have examined the potential of corals, the fundamental organisms of coral reefs, to monitor nickel (Ni) contamination in tropical marine ecosystems. In an effort to bridge this gap, the present work investigated the bioaccumulation of (63)Ni in the scleractinian coral Stylophora pistillata and in its isolated zooxanthellae Symbiodinium, using radiotracer techniques. Results highlight the high capacities of coral tissues (zooxanthellae and host tissues) to efficiently bioconcentrate (63)Ni compared to skeleton (Concentration Factors CF at 14 days of exposure are 3 orders of magnitude higher in tissues than in skeleton). When non-contaminated conditions were restored, (63)Ni was more efficiently retained in skeleton than in coral tissues, with biological half-lives (Tb1/2) of 44.3 and 6.5 days, respectively. In addition, our work showed that Symbiodinium bioconcentrated (63)Ni exponentially, with a vol/vol concentration factor at steady state (VCFSS) reaching 14,056. However, compilation of our results highlighted that despite efficient bioconcentration of (63)Ni in Symbiodinium, their contribution to the whole (63)Ni accumulation in coral nubbins represents less than 7%, suggesting that other biologically controlled processes occur in coral host allowing such efficient bioconcentration in coral tissues. PMID- 27192480 TI - In vitro exposure of Ulva lactuca Linnaeus (Chlorophyta) to gasoline - Biochemical and morphological alterations. AB - Refined fuels have considerable share of pollution of marine ecosystems. Gasoline is one of the most consumed fuel worldwide, but its effects on marine benthic primary producers are poorly investigated. In this study, Ulva lactuca was chosen as a biological model due to its cosmopolitan nature and tolerance to high levels and wide range of xenobiotics and our goal was to evaluate the effects of gasoline on ultrastructure and metabolism of that seaweed. The experimental design consisted of in vitro exposure of U. lactuca to four concentrations of gasoline (0.001%, 0.01%, 0.1%, and 1.0%, v/v) over 30 min, 1 h, 12 h, and 24 h, followed by cytochemical, SEM, and biochemical analysis. Increase in the number of cytoplasmic granules, loss of cell turgor, cytoplasmic shrinkage, and alterations in the mucilage were some of the ultrastructural alterations observed in thalli exposed to gasoline. Decrease in carotenoid and polyphenol contents, as well as increase of soluble sugars and starch contents were associated with the time of exposure to the xenobiotic. In combination, the results revealed important morphological and biochemical alterations in the phenotype of U. lactuca upon acute exposure to gasoline. This seaweed contain certain metabolites assigned as candidates to biomarkers of the environmental stress investigated and it is thought to be a promise species for usage in coastal ecosystems perturbation monitoring system. In addition, the findings suggest that U. lactuca is able to metabolize gasoline hydrocarbons and use them as energy source, acting as bioremediator of marine waters contaminated by petroleum derivatives. PMID- 27192481 TI - Characterization of dissolved organic nitrogen in wet deposition from Lake Erhai basin by using ultrahigh resolution FT-ICR mass spectrometry. AB - Dissolved Organic Nitrogen (DON) of wet deposition in Erhai basin (EWD) was characterized at the molecular level by using electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI FT-ICR MS). The structure and composition of DON were investigated by the combined ESI FT-ICR MS, UV-Vis absorbance and fluorescence techniques. The FT-ICR MS measurements indicate that a large (~790) number of organic species present in the wet deposition, in which DON account for 18.3%, with most of DON containing a single nitrogen atom. The typical relative molecular mass of the DON species was found to be in the range of 200-400 Da. Approximately 57.2% of DON species are highly unsaturated (DBE (Double Bond Equivalent) > 5) with the nitrogen- and sulfur containing species, which are probably represented mainly by active nitrooxy organosulfates, accounting for ~ 19.3% of the total DON. The low average SUVA254 and A253/A203 values (0.02 and 0.06, respectively), indicates that the aromaticity of the EWD samples is particularly weak. The average values of E2/E3 and E4/E6 in the EWD samples were 6.84 and 1.84, respectively. This is a clear indication of the low degree of humification of EWD samples, in agreement with ESI FT-ICR MS measurements. Our study demonstrates that multiple experimental techniques combined with FT-ICR MS, UV-Vis absorbance and fluorescence can be efficiently used for in-depth studying the DON at the molecular level. Thus it allows us to achieve a deep and insightful understanding of the DON structure and composition. PMID- 27192487 TI - Unexpected Metabolic Reactions and Secondary Targets of Pesticide Action. AB - Pesticides provide a fascinating combination of substituents not present in other environmental chemicals, leading to unexpected metabolites and toxicological effects in pests, mammals, and other organisms. The parent compound and/or metabolites of some pesticides have multiple targets, requiring identification of the causal agents and their modes of action. This review considers a few of the author's observations in the past six decades, some solved and others still puzzling. It illustrates that a new substituent combination not only confers specific chemical and physical properties to a class of compounds but often yields metabolites with a surprising variety of biological activities. Examples considered include proinsecticides, procyclic phosphates, CYP inhibitors as synergists, thiocarbamate sulfoxides, promutagens, carcinogens, and hepatotoxins, and stress tolerance inducers in plants. Although the discoveries considered are based on pesticide toxicology, they are broadly applicable to environmental toxicology and xenobiotics in animals, plants, and microorganisms. PMID- 27192486 TI - Effects of Sex and Notch Signaling on the Osteocyte Cell Pool. AB - Osteocytes play a fundamental role in mechanotransduction and skeletal remodeling. Sex is a determinant of skeletal structure, and female C57BL/6J mice have increased osteoblast number in cancellous bone when compared to male mice. Activation of Notch in the skeleton causes profound cell-context dependent changes in skeletal physiology. To determine the impact of sex and of Notch signaling on the osteocyte cell pool, we analyzed cancellous and cortical bone of 1-6-month-old C57BL/6J or 129SvJ/C57BL/6J mice and determined the osteocyte number/area. There was an age-dependent decline in osteocyte number in cancellous bone of male but not female mice, so that 6-month-old female mice had a greater number of osteocytes than male littermates. Although differences between male and female mice were modest, female mice had ~10-15% greater number of osteocytes/area. RNA sequence analysis of osteocyte-rich preparations did not reveal differences between sexes in the expression of genes known to influence bone homeostasis. Neither the activation of Notch1 nor the concomitant inactivation of Notch1 and Notch2 in Osterix (Sp7) or Dentin matrix protein 1 (Dmp1) expressing cells had a pronounced and consistent effect on cancellous or cortical bone osteocyte number in either sex. Moreover, inactivation of Notch1 and Notch2 in Dmp1 expressing cells did not influence the bone loss in a muscle immobilization model of skeletal unloading. In conclusion, cancellous bone osteocytes decline with age in male mice, cortical osteocytes are influenced by sex in younger mice, but osteocyte cell density is not affected substantially by Notch signaling. J. Cell. Physiol. 232: 363-370, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27192488 TI - Resistance to 3-HTMC-Induced Apoptosis Through Activation of PI3K/Akt, MEK/ERK, and p38/COX-2/PGE2 Pathways in Human HT-29 and HCT116 Colorectal Cancer Cells. AB - Increasing incidence and mortality of colorectal cancer brings the necessity to uncover new possibilities in its prevention and treatment. Chalcones have been identified as interesting compounds having chemopreventive and antitumor properties. In this study, we investigated the effects of the synthetic chalcone derivative 3-hydroxy-3',4,4',5'-tetra-methoxy-chalcone (3-HTMC) on proliferation, cell cycle distribution, apoptosis, and its mechanism of action in human colorectal HT-29 (COX-2 sufficient) and HCT116 (COX-2 deficient) cancer cells. We showed that 3-HTMC decreased cell viability in a dose-dependent manner with a more potent antiproliferative effect on HCT116 than HT-29 cells. Flow cytometric analysis revealed G2 /M cell cycle accumulation in HT-29 cells and significant G2 /M arrest in HCT116 cells with a subsequent apoptosis shown by appearance of Sub G1 peak. We demonstrated that 3-HTMC treatment on both cell lines induced apoptotic process associated with overexpression of death receptor DR5, activation of caspase-8 and -3, PARP cleavage, and DNA fragmentation. In addition, 3-HTMC induced activation of PI3K/Akt and MEK/ERK principal survival pathways which delay 3-HTMC-induced apoptosis in both cell lines. Furthermore, COX-2 overexpression in HT-29 cells contributes to apoptosis resistance which explains the difference of sensitivity between HT-29 and HCT116 cells to 3-HTMC treatment. Even if resistance mechanisms to apoptosis reduced chalcone antitumoral potential, our results suggest that 3-HTMC may be considered as an interesting compound for colorectal cancer therapy or chemoprevention. J. Cell. Biochem. 117: 2875-2885, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27192489 TI - The Potential Use of Forensic DNA Methods Applied to Sand Fly Blood Meal Analysis to Identify the Infection Reservoirs of Anthroponotic Visceral Leishmaniasis. AB - BACKGROUND: In the Indian sub-continent, visceral leishmaniasis (VL), also known as kala azar, is a fatal form of leishmaniasis caused by the kinetoplastid parasite Leishmania donovani and transmitted by the sand fly Phlebotomus argentipes. VL is prevalent in northeast India where it is believed to have an exclusive anthroponotic transmission cycle. There are four distinct cohorts of L. donovani exposed individuals who can potentially serve as infection reservoirs: patients with active disease, cured VL cases, patients with post kala azar dermal leishmaniasis (PKDL), and asymptomatic individuals. The relative contribution of each group to sustaining the transmission cycle of VL is not known. METHODOLOGY/PRINCIPAL FINDINGS: To answer this critical epidemiological question, we have addressed the feasibility of an approach that would use forensic DNA methods to recover human DNA profiles from the blood meals of infected sand flies that would then be matched to reference DNA sampled from individuals living or working in the vicinity of the sand fly collections. We found that the ability to obtain readable human DNA fingerprints from sand flies depended entirely on the size of the blood meal and the kinetics of its digestion. Useable profiles were obtained from most flies within the first 24 hours post blood meal (PBM), with a sharp decline at 48 hours and no readable profiles at 72 hours. This early time frame necessitated development of a sensitive, nested-PCR method compatible with detecting L. donovani within a fresh, 24 hours blood meal in flies fed on infected hamsters. CONCLUSION/SIGNIFICANCE: Our findings establish the feasibility of the forensic DNA method to directly trace the human source of an infected blood meal, with constraints imposed by the requirement that the flies be recovered for analysis within 24 hours of their infective feed. PMID- 27192490 TI - New Eocene Coleoid (Cephalopoda) Diversity from Statolith Remains: Taxonomic Assignation, Fossil Record Analysis, and New Data for Calibrating Molecular Phylogenies. AB - New coleoid cephalopods are described from statolith remains from the Middle Eocene (Middle Lutetian) of the Paris Basin. Fifteen fossil statoliths are identified and assigned to the Sepiidae (Sepia boletzkyi sp. nov.,? Sepia pira sp. nov.), Loliginidae (Loligo clarkei sp. nov.), and Ommastrephidae (genus indet.) families. The sediments containing these fossils indicate permanent aquatic settings in the infralittoral domain. These sediments range in age from 46 Mya to 43 Mya. Analysis of the fossil record of statoliths (from findings described here, together with a review of previously published data) indicates marked biases in our knowledge. Fossil statoliths are known from as far back as the Early Jurassic (199.3 to 190.8 Mya) but surprisingly, to the best of our knowledge, no record occurs in the Cretaceous. This is a "knowledge bias" and clearly calls for further studies. Finally, we attempt to compare findings described here with fossils previously used to constrain divergence and/or diversification ages of some coleoid subclades in molecular phylogenies. This comparison clearly indicates that the new records detailed here will challenge some estimated divergence times of coleoid cephalopod subclades. PMID- 27192492 TI - Risk Factors for Seabird Bycatch in a Pelagic Longline Tuna Fishery. AB - Capture in global pelagic longline fisheries threatens the viability of some seabird populations. The Hawaii longline tuna fishery annually catches hundreds of seabirds, primarily Laysan (Phoebastria immutabilis) and black-footed (P. nigripes) albatrosses. Since seabird regulations were introduced in 2001, the seabird catch rate has declined 74%. However, over the past decade, seabird catch levels significantly increased due to significant increasing trends in both effort and nominal seabird catch rates. We modelled observer data using a spatio temporal generalized additive mixed model with zero-inflated Poisson likelihood to determine the significance of the effect of various risk factors on the seabird catch rate. The seabird catch rate significantly increased as annual mean multivariate ENSO index values increased, suggesting that decreasing ocean productivity observed in recent years in the central north Pacific may have contributed to the increasing trend in nominal seabird catch rate. A significant increasing trend in number of albatrosses attending vessels, possibly linked to declining regional ocean productivity and increasing absolute abundance of black footed albatrosses, may also have contributed to the increasing nominal seabird catch rate. Largest opportunities for reductions are through augmented efficacy of seabird bycatch mitigation north of 23 degrees N where mitigation methods are required and during setting instead of during hauling. Both side vs. stern setting, and blue-dyed vs. untreated bait significantly reduced the seabird catch rate. Of two options for meeting regulatory requirements, side setting had a significantly lower seabird catch rate than blue-dyed bait. There was significant spatio-temporal and seasonal variation in the risk of seabird capture with highest catch rates in April and May and to the northwest of the main Hawaiian Islands. PMID- 27192491 TI - Prescribing of Antidiabetic Medicines before, during and after Pregnancy: A Study in Seven European Regions. AB - AIM: To explore antidiabetic medicine prescribing to women before, during and after pregnancy in different regions of Europe. METHODS: A common protocol was implemented across seven databases in Denmark, Norway, The Netherlands, Italy (Emilia Romagna/Tuscany), Wales and the rest of the UK. Women with a pregnancy starting and ending between 2004 and 2010, (Denmark, 2004-2009; Norway, 2005 2010; Emilia Romagna, 2008-2010), which ended in a live or stillbirth, were identified. Prescriptions for antidiabetic medicines issued (UK) or dispensed (non-UK) during pregnancy and/or the year before or year after pregnancy were identified. Prescribing patterns were compared across databases and over calendar time. RESULTS: 1,082,673 live/stillbirths were identified. Pregestational insulin prescribing during the year before pregnancy ranged from 0.27% (CI95 0.25-0.30) in Tuscany to 0.45% (CI95 0.43-0.47) in Norway, and increased between 2004 and 2009 in all countries. During pregnancy, insulin prescribing peaked during the third trimester and increased over time; third trimester prescribing was highest in Tuscany (2.2%) and lowest in Denmark (0.5%). Of those prescribed an insulin during pregnancy, between 50.5% in Denmark and 88.8% in the Netherlands received an insulin analogue alone or in combination with human insulin, this proportion increasing over time. Oral products were mainly metformin and prescribing was highest in the 3 months before pregnancy. Metformin use during pregnancy increased in some countries. CONCLUSION: Pregestational diabetes is increasing in many areas of Europe. There is considerable variation between and within countries in the choice of medication for treating pregestational diabetes in pregnancy, including choice of insulin analogues and oral antidiabetics, and very large variation in the treatment of gestational diabetes despite international guidelines. PMID- 27192493 TI - Errors in Data. PMID- 27192494 TI - Correction: Effect of Providing Multiple Micronutrients in Powder through Primary Healthcare on Anemia in Young Brazilian Children: A Multicentre Pragmatic Controlled Trial. AB - [This corrects the article DOI: 10.1371/journal.pone.0151097.]. PMID- 27192495 TI - The Keap1-Nrf2-ARE Pathway As a Potential Preventive and Therapeutic Target: An Update. AB - The Keap1-Nrf2-ARE ((Kelch-like ECH-Associating protein 1) nuclear factor erythroid 2 related factor 2-antioxidant response element) pathway is one of the most important defense mechanisms against oxidative and/or electrophilic stresses, and it is closely associated with inflammatory diseases, including cancer, neurodegenerative diseases, cardiovascular diseases, and aging. In recent years, progress has been made in strategies aimed at modulating the Keap1-Nrf2 ARE pathway. The Nrf2 activator DMF (Dimethylfumarates) has been approved by the FDA as a new first-line oral drug to treat patients with relapsing forms of multiple sclerosis, while a phase 3 study of another promising candidate, CDDO Me, was terminated for safety reasons. Directly inhibiting Keap1-Nrf2 protein protein interactions as a novel Nrf2-modulating strategy has many advantages over using electrophilic Nrf2 activators. The development of Keap1-Nrf2 protein protein interaction inhibitors has become a topic of intense research, and potent inhibitors of this target have been identified. In addition, inhibiting Nrf2 activity has attracted an increasing amount of attention because it may provide an alternative cancer therapy. This review summarizes the molecular mechanisms and biological functions of the Keap1-Nrf2-ARE system. The main focus of this review is on recent progress in studies of agents that target the Keap1-Nrf2-ARE pathway and the therapeutic applications of such agents. PMID- 27192496 TI - Metagenomic assessment of the microbial diversity in ground pork products from markets in the North Central Region of South Korea. AB - The purpose of this study was to characterize the microbial community in ground pork using molecular approaches. Forty six ground pork products were purchased from local stores in the north central area of South Korea. Aerobic plate counts varied 4.23 +/- 5.14 * 10(5) CFU/g with the range between 5.00 * 10(3) and 1.85 * 10(6) CFU/g for ground pork samples. Four ground meat samples were further processed for metagenomic analysis. Pseudomonas species was the most relative abundant with a wide range occurring (1.72 to 77.7%) as part of the microbial genera in ground pork. Bacteria such as Carnobacterium, Yersinia, Photobacterium were also identified in ground pork. Despite the prominence of certain genera across all samples there was still extensive microbial diversity among ground pork products that originated from different slaughter houses and were processed in different markets. Such diversity indicates that designing interventions to extend shelf life may be hampered by the extensive variability in the microbial consortia associated with pork products. However, this diversity may be useful for developing microbial traceability signatures unique to a slaughter house or a particular market. PMID- 27192497 TI - Quantitative magnetic resonance arthrography in patients with femoroacetabular impingement. AB - PURPOSE: Quantitative MRI (QMRI) of the hip with sequences such as T1rho and T2 mapping has been utilized to detect early changes in cartilage matrix composition. However, QMRI has not been performed in the presence of intra articular contrast. Thus the purpose of this study was to evaluate the feasibility and use of QMRI during MR-arthrography (MRA) in femoracetabular impingement (FAI) patients. MATERIALS AND METHODS: Using a 3 Tesla MR-scanner, 10 FAI patients underwent a unilateral MRA and standard MRI of the hip joint. Global and sub-regional T1rho and T2 relaxation times of the acetabular and femoral articular cartilage were computed in the MRA and MRI assessments and agreement of these values were assessed using the Krippendorff's alpha (alpha) coefficient and linear regression (MU). T1rho and T2 relaxation times between the MRA and MRI were compared using a repeated measures analysis of variance. RESULTS: Both global and sub-regional T1rho and T2 relaxation times demonstrated strong agreement (alpha > 0.83; MU > 0.85) independent of intra-articular contrast. Also, global and sub-regional acetabular T1rho (P = 0.72) and T2 (P = 0.94), as well as femoral T1rho , relaxation times were similar between MRA and MRI (P = 0.73) yet femoral T2 relaxation times decreased when using intra-articular contrast (P = 0.04). CONCLUSION: This study demonstrated the feasibility of T1rho and T2 mapping for use in hip MRA with FAI patients. The inclusion of QMRI in MRA provides a quantitative assessment of the effects of FAI on hip joint articular cartilage while allowing for detailed assessment of labral pathology with the use of intra-articular contrast. J. Magn. Reson. Imaging 2016;44:1539-1545. PMID- 27192498 TI - Possible Case of Novel Spotted Fever Group Rickettsiosis in Traveler Returning to Japan from India. AB - A 60-year-old woman experienced fever, headache, rash, and altered vision after returning to Japan from India. Testing detected elevated antibody titers to spotted fever group rickettsia; PCR on blood yielded positive results for the rickettsial outer membrane protein A gene. We isolated a unique rickettsial agent and performed a full-genome analysis. PMID- 27192499 TI - Image Quality in Oncologic Chest Computerized Tomography With Iterative Reconstruction: A Phantom Study. AB - OBJECTIVE: The purpose of this study was to validate iterative reconstruction technique in oncologic chest computed tomography (CT). METHODS: An anthropomorphic thorax phantom with 4 simulated tumors was scanned on a 64-slice CT scanner with 2 different iterative reconstruction techniques: one model based (MBIR) and one hybrid (ASiR). Dose levels of 14.9, 11.1, 6.7, and 0.6 mGy were used, and all images were reconstructed with filtered back projection (FBP) and both iterative reconstruction algorithms. Hounsfield units (HU) and absolute noise were measured in the tumors, lung, heart, diaphragm, and muscle. Contrast to-noise ratios (CNRs) and signal-to-noise ratios (SNRs) were calculated. RESULTS: Model-based iterative reconstruction (MBIR) increased CNRs of the tumors (21.1-192.2) and SNRs in the lung (-49.0-165.6) and heart (3.1-8.5) at all dose levels compared with FBP (CNR, 1.1-23.0; SNR, -7.5-31.6 and 0.2-1.1) and with adaptive statistical iterative reconstruction (CNR, 1.2-33.2; SNR, -7.3-37.7 and 0.2-1.5). At the lowest dose level (0.6 mGy), MBIR reduced the cupping artifact (HU range: 17.0 HU compared with 31.4-32.2). An HU shift in the negative direction was seen with MBIR. CONCLUSIONS: Quantitative image quality parameters in oncologic chest CT are improved with MBIR compared with FBP and simpler iterative reconstruction algorithms. Artifacts at low doses are reduced. A shift in HU values was shown; thus, absolute HU values should be used with care. PMID- 27192500 TI - Role of Cardiac Computed Tomography in the Evaluation of Coronary Artery Stenosis in Patients With Ascending Aorta Aneurysm Detected at Transthoracic Echocardiography. AB - OBJECTIVE: The aim of our study was to evaluate the diagnostic performance of cardiac computed tomography (CCT) in the evaluation of coronary artery stenosis in patients with ascending aorta aneurysm detected at transthoracic echocardiography. METHODS: We conducted a retrospective analysis of patients with an aneurysm 45 mm or greater at transthoracic echocardiography who underwent CCT from 2012 to 2014 in our hospital. We calculated the sensitivity, specificity, and positive and negative predictive values of CCT for the assessment of coronary artery stenosis (<50% or >=50% stenosis) in patients who underwent conventional coronary angiography. RESULTS: We included 104 patients (73 men, aged 64 [SD, 10.8] years) in our study. Obstructive coronary artery disease was found in 22.1% of patients. Sensitivity, specificity, and positive and negative predictive values of CCT for detecting significant stenoses were 100%, 98%, and 82% and 100% on a segment-by-segment analysis and 100%, 83%, and 65% and 100% on a per-patient analysis, respectively. CONCLUSIONS: Cardiac computed tomography provides a comprehensive evaluation of ascending aorta aneurysms and coronary artery tree. PMID- 27192501 TI - Diffusion-Weighted Breast Magnetic Resonance Imaging: A Semiautomated Voxel Selection Technique Improves Interreader Reproducibility of Apparent Diffusion Coefficient Measurements. AB - OBJECTIVE: To determine whether a semiautomated voxel selection technique improves interreader reproducibility for breast apparent diffusion coefficient (ADC) measurements. METHODS: Three readers retrospectively performed ADC measurements of 31 breast lesions (16 malignant, 15 benign) and contralateral normal tissue in 26 women both unassisted (manual method) and assisted by a semiautomated software tool that excludes voxels below a dynamically specified signal intensity threshold. Reproducibility between readers for each technique was assessed by Bland-Altman analysis and concordance correlation coefficients (CCCs). RESULTS: Differences between readers' measured ADCs of lesions were smaller with the semiautomated tool vs the manual method. Concordance correlation coefficients for each reader pair were greater with the semiautomated tool for lesions (mean CCC difference, 0.11; 95% confidence interval, 0.04-0.26). For normal tissue, reader agreement was lower than for lesions and did not differ based on software tools (mean CCC difference, 0.00; 95% confidence interval, 0.14 to 0.13). CONCLUSIONS: A semiautomated voxel selection tool can improve interreader reproducibility of breast lesion ADC measures. PMID- 27192502 TI - The Use of Breast Magnetic Resonance Imaging Parameters to Identify Possible Signaling Pathways of a Serum Biomarker, HE4. AB - OBJECTIVES: This study aimed to investigate the relationship between breast magnetic resonance imaging (MRI) parameters; clinical features such as age, tumor diameter, N, T, and TNM stages; and serum human epididymis protein 4 (HE4) levels in patients with breast carcinoma and use this as a means of estimating possible signaling pathways of the biomarker, HE4. METHODS: Thirty-seven patients with breast cancer were evaluated by breast MRI and serum HE4 levels before therapy. Correlations between parameters including age, tumor diameter T and N, dynamic curve type, enhancement ratio (ER), slope washin (S-WI), time to peak (TTP), slope washout (S-WO), and the serum level of HE4 were investigated statistically. Human epididymis protein 4 levels of early and advanced stage of disease were also compared statistically. RESULTS: Breast MRI parameters showed correlation to serum HE4 levels and correlations were statistically significant. Of these MRI parameters, S-WI had higher correlation coefficient than the others. Human epididymis protein 4 levels were not statistically different in early and advanced stage of disease. CONCLUSIONS: High correlation with MRI parameters related to neoangiogenesis may indicate signaling pathway of HE4. PMID- 27192503 TI - Correction of Motion Artifacts From Shuttle Mode Computed Tomography Acquisitions for Body Perfusion Imaging Applications. AB - OBJECTIVE: The aim of this study was to investigate the feasibility of shuttle mode computed tomography (CT) technology for body perfusion applications by quantitatively assessing and correcting motion artifacts. METHODS: Noncontrast shuttle-mode CT scans (10 phases, 2 nonoverlapping bed locations) were acquired from 4 patients on a GE 750HD CT scanner. Shuttling effects were quantified using Euclidean distances (between-phase and between-bed locations) of corresponding fiducial points on the shuttle and reference phase scans (prior to shuttle mode). Motion correction with nonrigid registration was evaluated using sum-of-squares differences and distances between centers of segmented volumes of interest on shuttle and references images. RESULTS: Fiducial point analysis showed an average shuttling motion of 0.85 +/- 1.05 mm (between-bed) and 1.18 +/- 1.46 mm (between phase), respectively. The volume-of-interest analysis of the nonrigid registration results showed improved sum-of-squares differences from 2950 to 597, between-bed distance from 1.64 to 1.20 mm, and between-phase distance from 2.64 to 1.33 mm, respectively, averaged over all cases. CONCLUSIONS: Shuttling effects introduced during shuttle-mode CT acquisitions can be computationally corrected for body perfusion applications. PMID- 27192504 TI - Adaptive prior weighting in generalized regression. AB - The prior distribution is a key ingredient in Bayesian inference. Prior information on regression coefficients may come from different sources and may or may not be in conflict with the observed data. Various methods have been proposed to quantify a potential prior-data conflict, such as Box's p-value. However, there are no clear recommendations how to react to possible prior-data conflict in generalized regression models. To address this deficiency, we propose to adaptively weight a prespecified multivariate normal prior distribution on the regression coefficients. To this end, we relate empirical Bayes estimates of prior weight to Box's p-value and propose alternative fully Bayesian approaches. Prior weighting can be done for the joint prior distribution of the regression coefficients or-under prior independence-separately for prespecified blocks of regression coefficients. We outline how the proposed methodology can be implemented using integrated nested Laplace approximations (INLA) and illustrate the applicability with a Bayesian logistic regression model for data from a cross sectional study. We also provide a simulation study that shows excellent performance of our approach in the case of prior misspecification in terms of root mean squared error and coverage. Supplementary Materials give details on software implementation and code and another application to binary longitudinal data from a randomized clinical trial using a Bayesian generalized linear mixed model. PMID- 27192506 TI - [Cognitive Training in Parkinson's Disease - A New Therapy Option?]. AB - Cognitive impairment is a frequent and clinically relevant symptom in patients with Parkinson's disease (PD). Given that pharmacological therapy options are limited, non-pharmacological interventions for the prevention and treatment of cognitive impairment in PD patients are attracting increasing interest. This review summarizes the current state of research regarding cognition-based interventions in PD patients. Eleven randomized controlled studies (RCT) were found in a systematic literature search, all of which used cognitive training (CT). These studies and a recently published meta-analysis demonstrate that especially executive and memory functions can be enhanced by CT in PD patients. Future studies examining CT or cognitive stimulation should include large PD samples with well-defined cognitive inclusion criteria so that clear therapy recommendations can be defined for PD patients without cognitive dysfunctions, those with mild cognitive impairment, and those with dementia. PMID- 27192505 TI - Use of a platelet-rich fibrin membrane to repair traumatic tympanic membrane perforations: a comparative study. AB - OBJECTIVES: (1) To evaluate the effects of a platelet-rich fibrin (PRF) membrane in the repair of traumatic tympanic membrane (TM) perforations; and (2) to compare the use of a PRF membrane with the paper patch technique with regard to recovery rates, healing time, and correction of the mean air-bone gap. METHODS: A randomized, prospective analysis was performed for 60 patients who were treated for traumatic TM perforations using one of the two methods. Closure rate, speed of healing, and hearing gain were compared between the PRF (Group 1) and paper patch (Group 2) groups. RESULTS: Closure was obtained in 28 (93%) perforations in Group 1 and 25 (83%) perforations in Group 2 (p > 0.05). On day 10, full closure of the TM was observed in 24 (80%) patients in Group 1 and 16 (53%) patients in Group 2 (p < 0.05). The improvement in the mean air-bone gap was 14.1 dB in Group 1 and 12.4 dB in Group 2 on post-operative day 45 (p < 0.05). CONCLUSIONS: In comparison with the paper patch method, PRF, a new method, provided more rapid healing with more successful audiological results, and with no requirement for a second procedure. PMID- 27192507 TI - Hydrophobic tail length plays a pivotal role in amyloid beta (25-35) fibril surfactant interactions. AB - The amyloid beta-peptide fragment comprising residues 25-35 (Abeta25-35 ) is known to be the most toxic fragment of the full length Abeta peptide which undergoes fibrillation very rapidly. In the present work, we have investigated the effects of the micellar environment (cationic, anionic, and nonionic) on preformed Abeta25-35 fibrils. The amyloid fibrils have been prepared and characterized by several biophysical and microscopic techniques. Effects of cationic dodecyl trimethyl ammonium bromide (DTAB), cetyl trimethylammonium bromide (CTAB), anionic sodium dodecyl sulfate (SDS), and nonionic polyoxyethyleneoctyl phenyl ether (Triton X-100 or TX) on fibrils have been studied by Thioflavin T fluorescence, UV-vis spectroscopy based turbidity assay and microscopic analyses. Interestingly, DTAB and SDS micelles were observed to disintegrate prepared fibrils to some extent irrespective of their charges. CTAB micelles were found to break down the fibrillar assembly to a greater extent. On the other hand, the nonionic surfactant TX was found to trigger the fibrillation process. The presence of a longer hydrophobic tail in case of CTAB is assumed to be a reason for its higher fibril disaggregating efficacy, the premise of their formation being largely attributed to hydrophobic interactions. Proteins 2016; 84:1213-1223. (c) 2016 Wiley Periodicals, Inc. PMID- 27192508 TI - Changes in sight. PMID- 27192509 TI - Benign skin disease with pustules in the newborn. AB - The neonatal period comprises the first four weeks of life. It is a period of adaptation where the skin often presents several changes: transient lesions, resulting from a physiological response, others as a consequence of transient diseases and some as markers of severe disorders. The presence of pustules in the skin of the newborn is always a reason for the family and for the assisting doctor to be worried, since the newborn is especially vulnerable to bacterial, viral or fungal infection. However, the majority of neonatal skin pustules is not infectious, comprising the benign neonatal pustulosis. Benign neonatal pustuloses are a group of clinical disease characterized by pustular eruptions in which a contagious agent is not responsible for its etiology. The most common ones are erythema toxicum neonatorum, the transient neonatal pustular melanosis and the benign cephalic pustulosis. These dermatoses are usually benign, asymptomatic and self-limited. It is important that the dermatologist and the neonatologist can identify benign and transient lesions, those caused by genodermatoses, and especially differentiate between neonates with systemic involvement from those with benign skin lesions, avoiding unnecessary diagnostic tests and worries. PMID- 27192510 TI - Photodynamic action of protoporphyrin IX derivatives on Trichophyton rubrum. AB - BACKGROUND: Dermatophytes are filamentous keratinophilic fungi. Trichophyton rubrum is a prevalent infectious agent in tineas and other skin diseases. Drug therapy is considered to be limited in the treatment of such infections, mainly due to low accessibility of the drug to the tissue attacked and development of antifungal resistance in these microorganisms. In this context, Photodynamic Therapy is presented as an alternative. OBJECTIVE: Evaluate, in vitro, the photodynamic activity of four derivatives of Protoporphyrin IX by irradiation with LED 400 nm in T. rubrum. METHOD: Assays were subjected to irradiation by twelve cycles of ten minutes at five minute intervals. RESULT: Photodynamic action appeared as effective with total elimination of UFCs from the second irradiation cycle. CONCLUSION: Studies show that the photodynamic activity on Trichophyton rubrum relates to a suitable embodiment of the photosensitizer, which can be maximized by functionalization of peripheral groups of the porphyrinic ring. PMID- 27192511 TI - Evaluation of dental material series from patients with dental prostheses and suspicion of delayed hypersensitivity. AB - BACKGROUND: Patients with oral sensitivity are common in our practice. Allergic contact dermatitis is one of the most frequent etiologies. OBJECTIVES: Evaluate oral contact dermatitis using the Brazilian standard series and complementary dental series in patients using dental prostheses, with or without oral complaints. Determine specific dental Brazilian series. METHODS: Patients using dental prostheses with or without oral complaints realized patch tests. Brazilian standard series and complementary dental series were used according to ICDRG recommendations. The results were analysed according to age, sex, race, atopic conditions and symptoms associated. RESULTS: From 54 patients tested, 34 (63%) were positive at least to one substance. Nineteen had oral complaints, such as burning mouth, itch or oral erythema. There was no association between atopic condition and tests results. Without the oral series, just 23(42,6%) patients had a positive result. Using the Brazilian standard series with the complementary dental series we improved the positivity of the patch test to 47%. CONCLUSION: In patients using prostheses and with oral complaints, patch tests with Brazilian standard series with complementary dental series improve the tests positivity. PMID- 27192513 TI - Are 2D:4D finger-length ratios an indicator of androgenetic alopecia in males? AB - BACKGROUND: Although the pathogenesis of androgenetic alopecia is not completely understood, the roles of genetic susceptibility and androgens are well-known. A lower ratio of the second digit (index finger = 2D) to the fourth digit (ring finger = 4D) length has been hypothesized to reflect prenatal androgen exposure and/or higher sensitivity to androgens. OBJECTIVES: To determine the relationship between the second to fourth digit length ratio and androgenetic alopecia. METHODS: Finger length measurements were made by a digital vernier calliper. Androgenetic alopecia severity was assessed using the Hamilton-Norwood scale. Subjects with an androgenetic alopecia score of grade III or more were included in the study. RESULTS: A total of 189 males with androgenetic alopecia and 171 healthy controls were enrolled in the study. The age range of participants was 19 65 years. The 2D:4D ratios in patients with androgenetic alopecia were significantly lower than those of healthy controls for the right hand; however, no significant difference was found for the left hand. Average 2D:4D ratios in androgenetic alopecia patients were also lower than in controls. No significant relationship was observed between androgenetic alopecia severity and 2D:4D ratios. CONCLUSION: Our data support the anatomical evidence of in utero androgen exposure and/or an individual's sensitivity to androgens in patients with androgenetic alopecia. Furthermore, the right hand 2D:4D ratio might be an indicator of androgenetic alopecia development. PMID- 27192512 TI - Assessment of adiposity in psoriatic patients by dual energy X-ray absorptiometry compared to conventional methods. AB - BACKGROUND: Obesity is considered a chronic low-grade inflammatory disease that shares mediators of inflammation with psoriasis, such as TNF-alpha and IL-6. The relationship between these two conditions involves factors such as predisposition and response to therapy, in addition to an association with cardiovascular disease. OBJECTIVES: The aim of the present study was to investigate the prevalence of adiposity as determined by body mass index (BMI), waist circumference (WC), and dual energy X-ray absorptiometry (DXA) evaluation in patients with psoriasis. METHODS: BMI, WC and body composition by DXA were measured in 42 psoriatic patients without joint complaints and in 41 control patients using standard procedures. In the comparison between cases and controls, we used Pearson's Chi2 test or Fisher's exact test, and the nonparametric Mann Whitney test. The difference between the diverse classification methods for obesity was evaluated using McNemar's test. To test the level of agreement between those variables, we used the weighted kappa coefficient. RESULTS: There was no difference in the prevalence of obesity among cases and controls. Both BMI and WC had low agreement with measures of body fat evaluated by DXA. With the use of DXA scanning, prevalence of overweight and obesity in patients with psoriasis was 83.3%, which constitutes a strong evidence of the need for intervention on this metabolic parameter. CONCLUSION: Dual energy X-ray absorptiometry was more capable of identifying obesity compared with BMI and WC both in psoriatic and control patients. PMID- 27192514 TI - Improvement of health-related quality of life and adherence to treatment with calcipotriol-betamethasone dipropionate gel in patients with psoriasis vulgaris. AB - BACKGROUND: Psoriasis is a common, chronic, recurrent, immune-mediated disorder of the skin and joints. It can have a significant negative impact on the physical, emotional and psychosocial wellbeing of affected patients. OBJECTIVES: To measure improvement in health-related QoL (HRQoL) in Greek patients with psoriasis vulgaris after a month of treatment with calcipotriol-betamethasone dipropionate gel; and evaluate adherence to treatment parameters. METHODS: The study included 394 psoriasis vulgaris patients from 16 private dermatological practices in Greece, all treated with calcipotriol-betamethasone dipropionate gel. They were evaluated at the first visit and after 4 weeks. Moreover, they completed the Dermatology Life Quality Index (DLQI), while other data such as disease severity, subjective symptoms and adherence, were collected. RESULTS: At week 4, the DLQI median was reduced by 3.5 points from the baseline (p<0.001; baseline and week 4 median: 4.5 and 1.0 respectively). Pruritus and sleep disorders also improved (p<0.001). Furthermore, 90.1% of the subjects fully adhered to treatment, with a 97.1% mean level of compliance. CONCLUSIONS: The convincing clinical results, with a distinct improvement in HRQoL, plus the high level of adherence due to its advantageous physical properties, make the calcipotriol-betamethasone dipropionate gel formulation an important, effective and well-tolerated topical therapy to treat psoriasis. PMID- 27192515 TI - Incidence of allergic contact sensitization in central Chinese subjects with chronic urticaria. AB - BACKGROUND: Chronic urticaria (CU) can be provoked by a wide variety of causes. Some studies suggest contact sensitization may play a role in the disease. OBJECTIVE: To investigate the incidence and distribution characteristics of allergic contact sensitization in central Chinese subjects with CU, and assess contact allergen avoidance measures in managing CU. METHODS: Patch tests were performed, following the recommended standard procedure, with 20 selected allergens, in line with the European baseline series. All subjects with positive results were prescribed appropriate avoidance measures for the sensitizing substances, while subjects with negative results served as the control group. CU severity was assessed daily from week1 to week4 and for each subject, applying the Urticaria Activity Score. RESULTS: 42.9% (233/543) of subjects with CU showed positive reactions to one or more contact allergen(s). Potassium dichromate, benzene mix and carba mix were more common in male patients, while nickel sulfate was more frequent in females. The positive rates for different allergens varied with age and occupation. The median (interquartile range) severity scores at week 1 were 20 (14-21) and 15 (14-27) for the allergen avoidance group and control group, respectively (P>0.05); and 12 (7-15) and 14 (12-17) at week 4 (P<0.001). CONCLUSION: The incidence of allergic contact sensitization in CU patients was high, and appropriate contact allergen avoidance measures benefitted CU management. Contact allergens may play a role in the pathogenic mechanism of CU and patch tests are an option for CU patients. PMID- 27192516 TI - Trichosporon isolation from human ungueal infections: is there a pathogenic role? AB - BACKGROUND: Although dermatophytes are considered the major cause of onychomycosis, many reports have incriminated non-dermatophyte moulds and yeasts in the disease's etiology. Successive Trichosporon isolation from onychomycosis has led to the genus being suspected as a nail primary pathogen. OBJECTIVE: To determine the prevalence of Trichosporon isolation in onychomycosis patients who attended a mycology diagnostic service in Rio de Janeiro, Brazil, between January 2003 and December 2006. The study also includes a worldwide review on Trichosporon isolation prevalence in ungueal disease, emphasizing T. ovoides. METHODS: This retrospective study was conducted with the support of staff from the Mycology Laboratory at the Dermatological Service of Rio de Janeiro's Santa Casa da Misericordia (MLDS). RESULTS: Mycological analysis provided positive results equaling 47/5036 (0.93%) for Trichosporon spp.; obtained mainly as a single agent (72.35%), and from mixed cultures (27.65%; X2= 6.397; p= 0.018). The great majority belongs to the T. ovoides species (91.5%; n=43), obtained as a single isolate (74.41%; n= 32/43; X2 = 7.023; p= 0.014). CONCLUSIONS: Although T. ovoides is classically associated as an etiologic agent of white piedra, this study highlights its potential as a human nail disease pathogen. Our study opens doors for future epidemiologic and virulence factors aimed at determining whether T. ovoides is an important causative agent of onychomycosis in Brazil. PMID- 27192517 TI - Translation, cultural adaptation and validation for Brazilian Portuguese of the Cardiff Acne Disability Index instrument. AB - BACKGROUND: The Cardiff Acne Disability Index was originally developed in English for measuring quality of life of acne patients. Considering the psychosocial impact of this disease, it is important to have instruments culturally and linguistically validated for use in Brazilian adolescents. OBJECTIVE: To translate the Cardiff Acne Disability Index into Brazilian Portuguese, culturally adapt it, and verify its reliability and validity in adolescent patients with acne. METHODS: In the first step, the Cardiff Acne Disability Index was translated and validated linguistically to Brazilian Portuguese in accordance with international guidelines published. In the second step, the validation of the Cardiff Acne Disability Index into Brazilian Portuguese instrument was performed, when patients aged from 12 to 20 years with acne were selected. The participants were interviewed to collect demographic data, submitted to the classification of acne by the Global Acne Grading System and invited to respond the Cardiff Acne Disability Index into Brazilian Portuguese version and DLQI (>16 years) or CDLQI (<=16 years). The internal consistency of Cardiff Acne Disability Index into Brazilian Portuguese was assessed by Cronbach's alpha coefficient and concurrent validity was measured by the Spearman correlation coefficient and Student 's t-test for paired samples. RESULTS: The study included 100 adolescents. The Cardiff Acne Disability Index into Brazilian Portuguese version showed good reliability and internal consistency (Cronbach's alpha = 0.73). The concurrent validity of the scale was supported by a strong and significant correlation with CDLQI / DLQI instruments (rs=0.802;p<0.001). CONCLUSIONS: Cardiff Acne Disability Index into Brazilian Portuguese version is a reliable, valid and valuable tool to measure the impact of acne on quality of life in adolescent patients. PMID- 27192518 TI - Effectiveness and safety of topical tacrolimus monotherapy for repigmentation in vitiligo: a comprehensive literature review. AB - Thus far, several small studies and case reports on the use of topical immunomodulators in vitiligo have been published. We undertook a comprehensive literature review, searching for studies evaluating clinical response to tacrolimus topical therapy for vitiligo. A search was performed on PubMed/Medline using the term "vitiligo", combined with "topical" and "ointment". Our inclusion criteria were: use of tacrolimus ointment as monotherapy to treat vitiligo. We found 29 studies from 2002 to 2014. Overall, 709 patients were treated in 29 studies. Pooling the lesions, 50% repigmentation of vitiligo patches was never achieved before 2 months of treatment, with a peak after 6 months of therapy. The best results were obtained on lesions of the cephalic region, especially the face, with tacrolimus 0.1% ointment two times daily. The percentage of non responsive patients ranged from 0% to 14%. Treatment was generally well tolerated; only localized adverse effects were reported. Our objective was to verify the effectiveness and safety of tacrolimus ointment monotherapy. It has good efficacy and tolerability. At present, only small trials and case series are available in the literature. Further, standardized investigations on a larger number of patients are needed. PMID- 27192519 TI - Leprosy among children under 15 years of age: literature review. AB - Leprosy is a chronic infectious disease caused by Mycobacterium leprae, representing a public health issue in some countries. Though more prevalent in adults, the detection of new cases in children under 15 years of age reveals an active circulation of bacillus, continued transmission and lack of disease control by the health system, as well as aiding in the monitoring of the endemic. Among patients under 15 years of age, the most affected age group is children between 10 and 14 years of age, although cases of patients of younger than 1 year of age have also been reported. Household contacts are the primary source of infection, given that caretakers, such as babysitters and others, must be considered in this scenario. Paucibacillary forms of the disease prevailed, especially borderline-tuberculoid leprosy, with a single lesion in exposed areas of the body representing the main clinical manifestation. Reactional states: Lepra reactions are rare, although some authors have reported high frequencies of this phenomenon, the most frequent of which is Type 1 Lepra Reaction. Peripheral nerve involvement has been described at alarming rates in some studies, which increases the chance of deformities, a serious problem, especially if one considers the age of these patients. The protective effect of BCG vaccination was found in some studies, but no consensus has been reached among different authors. Children must receive the same multidrug therapy regimen and the doses should, ideally, be calculated based on the child's weight. Adverse reactions to this therapy are rare within this age group. This article aims to review epidemiological, clinical, and therapeutic aspects of leprosy in patients under 15 years of age. PMID- 27192520 TI - Papulonodular secondary syphilis: a rare clinic presentation confirmed by serologic and histologic exams. AB - Syphilis is a sexually transmitted disease caused by Treponema pallidum and divided into three stages according to the duration of the disease: primary, secondary and tertiary. Secondary syphilis has diverse clinical presentations, such as papular-nodular lesions. This presentation is rare, with 15 cases reported in the literature over the past 20 years. We report a case of secondary syphilis with papular-nodular lesions in a healthy 63-year-old patient, who has presented treponema in immunohistochemical examination of the skin lesions. PMID- 27192521 TI - Scleroderma en coup de sabre treated with polymethylmethacrylate - Case report. AB - The scleroderma en coup de sabre is a variant of localized scleroderma that occurs preferentially in children. The disease progresses with a proliferative and inflammatory phase and later atrophy and residual deformity, which are treated with surgical techniques such as injectable fillers, transplanted or autologous fat grafting and resection of the lesion. Among the most widely used fillers is hyaluronic acid. However, there are limitations that motivate the search for alternatives, such as polymethylmethacrylate, a permanent filler that is biocompatible, non-toxic, non-mutagenic and immunologically inert. In order to illustrate its application, a case of scleroderma en coup de sabre in a 17-year old patient, who was treated with polymethylmethacrylate with excellent aesthetic results, is reported. PMID- 27192522 TI - Infantile multiple large pyogenic granuloma on burned skin. Case report and review of literature. AB - Pyogenic granuloma (PG) is a benign vascular lesion of the skin and mucous membranes, presenting as a solitary, red, pedunculated papule that bleeds easily and which appears to be a reactive vascular proliferation to minor injury. These lesions are more common in children and are mostly seen in exposed sites. Multiple disseminated PG is a rare condition. This report describes an infant with multiple, disseminated, pyogenic granulomas following burns from boiling milk. We reviewed literature published in English and found 9 cases. Six cases were provoked by hot milk, 2 by hot water, while the cause of the other case is unknown. Angiogiogenetic activity in milk may explain PG development in these patients. PMID- 27192523 TI - Cutaneous neonatal herpes simplex virus infection type 2: a case report. AB - Neonatal herpes is a serious condition. Newborns can be contaminated in utero via transplacental hematogenic transmission, upon delivery (the most frequent route), or during the postnatal period (indirect transmission). Optimal management requires prompt and accurate recognition, particularly in newborns, in order to prevent complications. Acyclovir is the treatment of choice, but its implementation is often delayed while awaiting test results, such as PCR and serology. Cytology for diagnostic purposes is rarely used in dermatology, despite the quick and reliable results. We report a case of neonatal herpes caused by type 2 herpes simplex virus diagnosed by cytology. PMID- 27192524 TI - Multifocal primary cutaneous extranodal NK/T lymphoma nasal type. AB - Nasal type extranodal NK/T-cell lymphoma is a distinct entity according to the World Health Organization classification. Although 60% to 90% of patients with this disease present with a destructive mass in the midline facial tissues, it may also primarily or secondarily involve extranasal sites, like the skin. We report the case of a 77-year-old patient that came to our department with erythematous plaques of the right leg and eczematous lesions of the trunk. These lesions were biopsied and the patient was diagnosed with extranodal NK/T-cell lymphoma, nasal type. He was treated with multi-agent systemic chemotherapy but died 5 months after diagnosis. This case highlights the rarity and variability of cutaneous features of this disease and its aggressive course and poor prognosis. PMID- 27192525 TI - Paronychia and granulation tissue formation during treatment with isotretinoin. AB - This paper describes the association of two unusual side effects of treatment with isotretinoin for severe acne: paronychia and excess granulation tissue in the nails furrows. We report a case of male patient aged 19 years, who in the course of the 36th week of treatment with isotretinoin for acne grade III showed erythema, edema, excess granulation tissue and onychocryptosis in various nail beds of hands and feet, with no history of trauma associated. A literature review revealed few reports of these adverse events, and two clinical patterns of exuberant granulation tissue has been described: one in periungual location and other in lesions of previous acne. The rarity and lack of knowledge on the best treatment for granuloma-like reactions make this theme a considerable challenge. PMID- 27192526 TI - Hyaline fibromatosis syndrome: cutaneous manifestations. AB - Hyaline fibromatosis syndrome is the current name for clinical manifestations of diseases previously known as "infantile systemic hyalinosis" and "juvenile hyaline fibromatosis". The authors report representative clinical cases of each one of the above subtypes with emphasis on cutaneous manifestations and difficulties for early diagnosis in this syndrome, essentially of multidisciplinary approach. PMID- 27192528 TI - Penile ulcer as a specific clinical manifestation of Waldenstrom's macroglobulinemia. AB - Waldenstrom's macroglobulinemia is considered a lymphoma by the World Health Organization. Cutaneous lesions, particularly of a specific type, are rare occurring in 5% of patients. What draws attention in this case is the unusual cutaneous clinical manifestation and its location on the genitals, which has not been described in researched literature, therefore imposing differential diagnosis with other etiologies of genital ulcers. PMID- 27192527 TI - Sarcoidosis and chronic hepatitis C: treatment with prednisone and colchicine. AB - Sarcoidosis is a disease which still has uncertain etiology. Possible environmental causes are cited in the literature, like organic and inorganic particles and infectious agents. Recent studies have demonstrated the occurrence of sarcoidosis in patients with chronic C hepatitis; however, this association remains without statistical or causal evidence. In this report a case of sarcoidosis associated with chronic hepatitis C will be described, with subcutaneous lesions, considered rare, and good response to treatment with colchicine and prednisone. The hepatitis C virus was isolated in sarcoid tissue and the association between the two diseases will be discussed. PMID- 27192529 TI - Isolated plexiform neurofibroma mimicking a vascular lesion. AB - Plexiform neurofibromas are benign tumors originating from peripheral nerve sheaths, generally associated with Neurofibromatosis Type 1 (NF1). They are diffuse, painful and sometimes locally invasive, generating cosmetic problems. This report discusses an adolescent patient who presented with an isolated, giant plexiform neurofibroma on her leg that was confused with a vascular lesion due to its clinical aspects. Once the diagnosis was confirmed by surgical biopsy, excision of the lesion was performed with improvement of the symptoms. PMID- 27192530 TI - Paracoccidioidomycosis and cryptococcosis with localized skin manifestations: report of two cases in the elderly. AB - Distinct cases of Paracoccidioidomycosis and Cryptococcosis with atypical and localized skin manifestation on the upper limbs of two elderly patients are reported. In the 2nd one, he presented asymptomatic pulmonary cancer; the blood tests for fungal infection were negative, and the etiologic agents were seen in skin biopsy samples. This report emphasizes the importance of the differential diagnosis of infectious diseases in elderly patients. PMID- 27192531 TI - Syndrome in question. AB - Neurofibromatosis is extremely variable in its presentation. Segmental neurofibromatosis (SNF), which corresponds to NF-type 5 in the Riccardi classification, is a rare disorder. It may go unrecognized if few lesions are observed. We present a case of segmental neurofibromatosis in a 28 year-old patient who presented with multiple papules and nodules distributed in dermatomal fashion on the trunk. The histopathological examination of the lesions revealed a non-encapsulated, well-circumscribed spindle cell neoplasm, which was consistent with neurofibromas. PMID- 27192532 TI - Bullous leukemia cutis mimicking facial cellulitis. AB - Bullous leukemia cutis is an uncommon clinical manifestation of cutaneous infiltration by leukemic cells, from B-cell chronic lymphocytic leukemia. We present the case of a 67-year-old, female, chronic lymphocytic leukemia patient. She was taking chlorambucil and developed facial edema with erythema and warmth, misjudged as facial cellulitis. Two days later, she developed bullous lesions in the arms, legs, neck and face. The histopathology of facial and bullous lesions confirmed leukemia cutis. All lesions disappeared following the administration of rituximab combined with cycles of fludarabine and cyclophosphamide. Although soft tissue infections are common complications in patients undergoing chemotherapy, leukemia cutis can also resemble cellulitis. PMID- 27192533 TI - Relationship between acne vulgaris and attention-deficit/hyperactivity disorder symptoms in a clinical sample of women. AB - Acne vulgaris has recently been reported to be associated with elevated rates of attention deficit/hyperactivity disorder in epidemiological studies. This report examines childhood and current attention-deficit/hyperactivity disorder symptoms in a clinical sample of female adults. Ninety-one women with acne vulgaris and 53 controls were included in this study. The aforementioned symptoms were measured in participants. No significant differences were found between patients and controls in any of the measurements. Contrary to the findings of epidemiological studies, this study did not uncover a link between acne vulgaris and attention deficit/hyperactivity disorder. PMID- 27192535 TI - Les Antigenes Des Membranes Basales Et Les Nephropathies. PMID- 27192534 TI - Modest Rise in Caesarean Section from 2000-2010: The Dutch Experience. AB - BACKGROUND: The caesarean delivery (CD) rate has risen in most countries over the last decades, but it remains relatively low in the Netherlands. Our objective was to analyse the trends of CD rates in various subgroups of women between 2000 and 2010, and identify the practice pattern that is attributable to the relative stability of the Dutch CD rate. METHODS: A total of 1,935,959 women from the nationwide Perinatal Registry of the Netherlands were included. Women were categorized into ten groups based on the modified CD classification scheme. Trends of CD rates in each group were described. RESULTS: The overall CD rate increased slightly from 14.0% in 2000-2001 to 16.7% in 2010. Fetal, early and late neonatal mortality rates decreased by 40-50% from 0.53%, 0.21%, 0.04% in 2000-2001 to 0.29%, 0.12%, 0.02% in 2010, respectively. During this period, the prevalence of non-vertex presentation decreased from 6.7% to 5.3%, even though the CD rate in this group was high. The nulliparous women with spontaneous onset of labor at term and a singleton child in vertex presentation had a CD rate of 9.9%, and 64.7% of multiparous women with at least one previous uterine scar and a singleton child in vertex presentation had a trial of labor and the success rate of vaginal delivery was 45.9%. CONCLUSIONS: The Dutch experience indicates that external cephalic version for breech presentation, keeping the CD rate low in nulliparous women and encouraging a trial of labor in multiparous women with a previous scar, could help to keep the overall CD rate steady. PMID- 27192536 TI - Serotypage Des Pneumocoques (Hemocultures Et Ponctions Tracheales), Sensibilite Aux Antibiotiques Et Considerations Sur L'Usage D'Un Vaccin Specifique. AB - 114 strains isolated by blood cultures and transtracheal aspirations were typed: serotypes 3 and 4 were largely predominant and a 14-valent vaccine (1, 2, 3, 4, 6, 8, 9, 12, 14, 19, 23, 25, 51, 56) should cover 67 % of these strains and protect 53 % of our patients because the efficacy of the vaccine is evaluated at 80 %. A controlled clinical trial seems to be necessary. We did not isolate any penicillin-resistant strain but 14 % of our strains were resistant to tetracycline. PMID- 27192537 TI - Evaluation Des Cephalosporins De La Deuxieme Generation: Cefamandole, Cefoxitine, Cefuroxime. PMID- 27192539 TI - Therapeutic augmentation of the growth hormone axis to improve outcomes following peripheral nerve injury. AB - INTRODUCTION: Peripheral nerve injuries often result in debilitating motor and sensory deficits. There are currently no therapeutic agents that are clinically available to enhance the regenerative process. Following surgical repair, axons often must regenerate long distances to reach and reinnervate distal targets. Progressive atrophy of denervated muscle and Schwann cells (SCs) prior to reinnervation contributes to poor outcomes. Growth hormone (GH)-based therapies have the potential to accelerate axonal regeneration while at the same time limiting atrophy of muscle and the distal regenerative pathway prior to reinnervation. AREAS COVERED: In this review, we discuss the potential mechanisms by which GH-based therapies act on the multiple tissue types involved in peripheral nerve regeneration to ultimately enhance outcomes, and review the pertinent mechanistic and translational studies that have been performed. We also address potential secondary benefits of GH-based therapies pertaining to improved bone, tendon and wound healing in the setting of peripheral nerve injury. EXPERT OPINION: GH-based therapies carry great promise for the treatment of peripheral nerve injuries, given the multi-modal mechanism of action not seen with other experimental therapies. A number of FDA-approved drugs that augment the GH axis are currently available, which may facilitate clinical translation. PMID- 27192540 TI - Role of Associated Defects in Oxygen Ion Conduction and Surface Exchange Reaction for Epitaxial Samaria-Doped Ceria Thin Films as Catalytic Coatings. AB - Samaria-doped ceria (SDC) thin films are particularly important for energy and electronic applications such as microsolid oxide fuel cells, electrolyzers, sensors, and memristors. In this paper, we report a comparative study investigating ionic conductivity and surface reactions for well-grown epitaxial SDC films varying the samaria doping concentration. With increasing doping above 20 mol % of samaria, an enhancement in the defect association is observed by Raman spectroscopy. The role of such associated defects on the films oxygen ion transport and exchange is investigated by electrochemical impedance spectroscopy and electrochemical strain microscopy (ESM). The measurements reveal that the ionic transport has a sharp maximum in ionic conductivity and drops in its activation energy down to 0.6 eV for 20 mol % doping. Increasing the doping concentration further up to 40 mol %, it raises the activation energy substantially by a factor of 2. We ascribe the sluggish transport kinetics to the "bulk" ionic-near ordering in case of the heavily doped epitaxial films. Analysis of the ESM first-order reversal curve measurements indicates that these associated defects may have a beneficial role by lowering the activation of the oxygen exchange "surface" reaction for heavily doped 40 mol % of samaria. In a model experiment, through a solid solution series of samaria doped ceria epitaxial films, we reveal that the occurrence of associated defects in the bulk affects the surface charging state of the SDC films to increase the exchange rates. The implication of these findings is the design of coatings with tuned oxygen surface exchange by controlling the bulk associated clusters for future electrocatalytic applications. PMID- 27192542 TI - Folliculocentric and Octagonal Scaly Papules. PMID- 27192544 TI - Does Emergency Department Use for Alcohol and Other Drug Use Cluster Geographically? A Population-Based Retrospective Cohort Study. AB - PURPOSE: To identify geographic areas in Alberta, Canada with higher numbers of adolescents with an emergency department (ED) presentation for a mental or behavioral disorder secondary to alcohol and other drug use. METHODS: A population-based cohort analysis of ED visits (n = 7787) by adolescents aged 15 17 years (n = 7238) during 2002-2011. We calculated sex-adjusted directly standardized rates (DSRs) and identified space-time clusters in health zones (North, Edmonton, Calgary, Central, and South). RESULTS: The North zone had higher DSRs compared to other areas. Clusters were identified in: (1) North, Edmonton, and northwest Central zones [relative risk (RR: 1.54; from 2004 to 2008); (2) western South and southern Calgary zones (RR: 1.58; from 2007 to 2011); and (3) northern South zone (RR: 2.38; from 2006 to 2007). CONCLUSIONS: The spatial scan can identify geographic areas of high health care use for specific health conditions. These results, in turn, can be used to inform health resource planning. PMID- 27192543 TI - Antibody Response and Disease Severity in Healthcare Worker MERS Survivors. AB - We studied antibody response in 9 healthcare workers in Jeddah, Saudi Arabia, who survived Middle East respiratory syndrome, by using serial ELISA and indirect immunofluorescence assay testing. Among patients who had experienced severe pneumonia, antibody was detected for >18 months after infection. Antibody longevity was more variable in patients who had experienced milder disease. PMID- 27192545 TI - Efficiency of Ozone Therapy in a Rat Model of Experimental Uveitis. AB - PURPOSE: To investigate efficiency of ozone therapy in uveitis. METHODS: A total of 24 albino Wistar rats were randomly assigned to four groups (n = 6); (a) control group; (b) sham group; (c) infliximab treatment group; (d) ozone therapy group. Vitreous haze scores of all groups were evaluated. Vitreous cytokine levels (TNF-alpha, IL-1, IL-6) measured by ELISA and eyes were enucleated for histopathologic examination. RESULTS: According to vitreous haze scores, there was statistically significant inflammation in Group (b) compared with Group (a), and there was less inflammation in infliximab and ozone groups compared with Group (b) (p < 0.05). Cytokine levels in infliximab and ozone groups were lower but not statistically significant when compared with Group (b) (p > 0.05). There was significantly less inflammation in histopathologic examination in treatment groups when compared with the sham group (p < 0.05). CONCLUSIONS: Clinical and histopathologic examination results indicate that systemic application of ozone may be efficient in the treatment of uveitis. PMID- 27192547 TI - TBDQ: A Pragmatic Task-Based Method to Data Quality Assessment and Improvement. AB - Organizations are increasingly accepting data quality (DQ) as a major key to their success. In order to assess and improve DQ, methods have been devised. Many of these methods attempt to raise DQ by directly manipulating low quality data. Such methods operate reactively and are suitable for organizations with highly developed integrated systems. However, there is a lack of a proactive DQ method for businesses with weak IT infrastructure where data quality is largely affected by tasks that are performed by human agents. This study aims to develop and evaluate a new method for structured data, which is simple and practical so that it can easily be applied to real world situations. The new method detects the potentially risky tasks within a process, and adds new improving tasks to counter them. To achieve continuous improvement, an award system is also developed to help with the better selection of the proposed improving tasks. The task-based DQ method (TBDQ) is most appropriate for small and medium organizations, and simplicity in implementation is one of its most prominent features. TBDQ is case studied in an international trade company. The case study shows that TBDQ is effective in selecting optimal activities for DQ improvement in terms of cost and improvement. PMID- 27192546 TI - Ultrastructural Changes Associated with Reversible Stiffening in Catch Connective Tissue of Sea Cucumbers. AB - The dermis of sea cucumbers is a catch connective tissue or a mutable collagenous tissue that shows rapid, large and reversible stiffness changes in response to stimulation. The main component of the dermis is the extracellular material composed of collagen fibrils embedded in a hydrogel of proteoglycans. The stiffness of the extracellular material determines that of the dermis. The dermis has three mechanical states: soft (Sa), standard (Sb) and stiff (Sc). We studied the ultrastructural changes associated with the stiffness changes. Transverse sections of collagen fibrils in the dermis showed irregular perimeters with electron-dense protrusions or arms that cross-bridged between fibrils. The number of cross-bridges increased in stiffer dermis. The distance between the fibrils was shorter in Sc than that in other states, which was in accord with the previous report that water exuded from the tissue in the transition Sb->Sc. The ultrastructure of collagen fibrils that had been isolated from the dermis was also studied. Fibrils aggregated by tensilin, which causes the transition Sa->Sb possibly through an increase in cohesive forces between fibrils, had larger diameter than those dispersed by softenin, which antagonizes the effect of tensilin. No cross-bridges were found in isolated collagen fibrils. From the present ultrastructural study we propose that three different mechanisms work together to increase the dermal stiffness. 1.Tensilin makes collagen fibrils stronger and stiffer in Sa->Sb through an increase in cohesive forces between subfibrils that constituted fibrils; 2. Cross-bridging by arms caused the fibrils to be a continuous network of bundles both in Sa->Sb and in Sb->Sc; 3. The matrix embedding the fibril network became stiffer in Sb->Sc, which was produced by bonding associated with water exudation. PMID- 27192541 TI - Variant ASGR1 Associated with a Reduced Risk of Coronary Artery Disease. AB - BACKGROUND: Several sequence variants are known to have effects on serum levels of non-high-density lipoprotein (HDL) cholesterol that alter the risk of coronary artery disease. METHODS: We sequenced the genomes of 2636 Icelanders and found variants that we then imputed into the genomes of approximately 398,000 Icelanders. We tested for association between these imputed variants and non-HDL cholesterol levels in 119,146 samples. We then performed replication testing in two populations of European descent. We assessed the effects of an implicated loss-of-function variant on the risk of coronary artery disease in 42,524 case patients and 249,414 controls from five European ancestry populations. An augmented set of genomes was screened for additional loss-of-function variants in a target gene. We evaluated the effect of an implicated variant on protein stability. RESULTS: We found a rare noncoding 12-base-pair (bp) deletion (del12) in intron 4 of ASGR1, which encodes a subunit of the asialoglycoprotein receptor, a lectin that plays a role in the homeostasis of circulating glycoproteins. The del12 mutation activates a cryptic splice site, leading to a frameshift mutation and a premature stop codon that renders a truncated protein prone to degradation. Heterozygous carriers of the mutation (1 in 120 persons in our study population) had a lower level of non-HDL cholesterol than noncarriers, a difference of 15.3 mg per deciliter (0.40 mmol per liter) (P=1.0*10(-16)), and a lower risk of coronary artery disease (by 34%; 95% confidence interval, 21 to 45; P=4.0*10( 6)). In a larger set of sequenced samples from Icelanders, we found another loss of-function ASGR1 variant (p.W158X, carried by 1 in 1850 persons) that was also associated with lower levels of non-HDL cholesterol (P=1.8*10(-3)). CONCLUSIONS: ASGR1 haploinsufficiency was associated with reduced levels of non-HDL cholesterol and a reduced risk of coronary artery disease. (Funded by the National Institutes of Health and others.). PMID- 27192548 TI - In situ speciation of dissolved inorganic antimony in surface waters and sediment porewaters: development of a thiol-based diffusive gradients in thin films technique for Sb(III). AB - Antimony is a priority environmental contaminant typically present as either the trivalent (Sb(III)) or the pentavalent (Sb(V)) oxidation state in aquatic systems. Both the toxicity and mobility of antimony are affected by its speciation, and thus the accurate measurement of antimony speciation is essential for investigating the behaviour of this contaminant in aquatic systems. Here we present a diffusive gradients in thin films (DGT) technique, which utilises a binding layer containing a thiol-based adsorbent (3-mercaptopropyl functionalised silica gel), for the selective measurement of Sb(III) in surface waters and sediment porewaters. We also evaluated the Metsorb DGT technique, which has been previously reported to accurately measure Sb(V), for its ability to accumulate Sb(III) and thus allow the measurement of total inorganic antimony. Both the mercapto-silica and Metsorb DGT techniques showed a high affinity for Sb(III), with uptake efficiencies >97%. Elution efficiencies of 86.9 +/- 2.6% and 88.1 +/- 1.2% were obtained for mercapto-silica and Metsorb, respectively, with 1 mol L( 1) H2O2 in 1 mol L(-1) NaOH. The accumulation of Sb(III) by these DGT techniques was linear with time (R(2) > 0.99) and unaffected by pH (4.07-8.05), ionic strength (0.001-1.0 mol L(-1) NaCl), bicarbonate (1-15 mmol L(-1)), and an artificial seawater matrix (pH 8.34; salinity 34.8). Finally, the mercapto-silica DGT technique was applied to measure porewater concentrations of Sb(III) and As(III) in a contaminated freshwater sediment at high resolution. PMID- 27192549 TI - Conformational States of HIV-1 Reverse Transcriptase for Nucleotide Incorporation vs Pyrophosphorolysis-Binding of Foscarnet. AB - HIV-1 reverse transcriptase (RT) catalytically incorporates individual nucleotides into a viral DNA strand complementing an RNA or DNA template strand; the polymerase active site of RT adopts multiple conformational and structural states while performing this task. The states associated are dNTP binding at the N site, catalytic incorporation of a nucleotide, release of a pyrophosphate, and translocation of the primer 3'-end to the P site. Structural characterization of each of these states may help in understanding the molecular mechanisms of drug activity and resistance and in developing new RT inhibitors. Using a 38-mer DNA template-primer aptamer as the substrate mimic, we crystallized an RT/dsDNA complex that is catalytically active, yet translocation-incompetent in crystals. The ability of RT to perform dNTP binding and incorporation in crystals permitted obtaining a series of structures: (I) RT/DNA (P-site), (II) RT/DNA/AZTTP ternary, (III) RT/AZT-terminated DNA (N-site), and (IV) RT/AZT-terminated DNA (N site)/foscarnet complexes. The stable N-site complex permitted the binding of foscarnet as a pyrophosphate mimic. The Mg(2+) ions dissociated after catalytic addition of AZTMP in the pretranslocated structure III, whereas ions A and B had re-entered the active site to bind foscarnet in structure IV. The binding of foscarnet involves chelation with the Mg(2+) (B) ion and interactions with K65 and R72. The analysis of interactions of foscarnet and the recently discovered nucleotide-competing RT inhibitor (NcRTI) alpha-T-CNP in two different conformational states of the enzyme provides insights for developing new classes of polymerase active site RT inhibitors. PMID- 27192550 TI - Learning image based surrogate relevance criterion for atlas selection in segmentation. AB - Picking geometrically relevant atlases from the whole training set is crucial to multi-atlas based image segmentation, especially with extensive data of heterogeneous quality in the Big Data era. Unfortunately, there is very limited understanding of how currently used image similarity criteria reveal geometric relevance, let alone the optimization of them. This paper aims to develop a good image based surrogate relevance criterion to best reflect the underlying inaccessible geometric relevance in a learning context. We cast this surrogate learning problem into an optimization framework, by encouraging the image based surrogate to behave consistently with geometric relevance during training. In particular, we desire a criterion to be small for image pairs with similar geometry and large for those with significantly different segmentation geometry. Validation experiments on corpus callosum segmentation demonstrate the improved quality of the learned surrogate compared to benchmark surrogate candidates. PMID- 27192551 TI - Drug release from liposome coated hydrogels for soft contact lenses: the blinking and temperature effect. AB - In this article, liposome-based coatings aiming to control drug release from therapeutic soft contact lenses (SCLs) materials are analyzed. A PHEMA based hydrogel material loaded with levofloxacin is used as model system for this research. The coatings are formed by polyelectrolyte layers containing liposomes of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and DMPC + cholesterol (DMPC + CHOL). The effect of friction and temperature on the drug release is investigated. The aim of the friction tests is to simulate the blinking of the eyelid in order to verify if the SCLs materials coated with liposomes are able to keep their properties, in particular the drug release ability. It was observed that under the study conditions, friction did not affect significantly the drug release from the liposome coated PHEMA material. In contrast, increasing the temperature of release leads to an increase of the drug diffusion rate through the hydrogel. This phenomenon is recorded both in the control and in the coated samples. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1799-1807, 2017. PMID- 27192552 TI - Decreased epithelial and plasma miR-181b-5p expression associates with airway eosinophilic inflammation in asthma. AB - BACKGROUND: Airway eosinophilic inflammation is a pivotal feature of asthma. Epithelial cells play critical roles in airway eosinophilia. We hypothesized that epithelial microRNAs (miRNAs) are involved in airway eosinophilia. OBJECTIVE: This study investigated the associations between epithelial and plasma miR-181b 5p and airway eosinophilic inflammation, and the possible mechanism by which miR 181b-5p participates in eosinophilic inflammation. METHODS: Epithelial miRNAs expression was profiled by miRNA array in eight subjects with asthma and four healthy controls. Epithelial miR-181b-5p expression was confirmed by quantitative PCR in the subjects for array experiment and another cohort including 21 subjects with asthma and 10 controls. Plasma miR-181b-5p was determined by quantitative PCR in 72 subjects with asthma and 35 controls. Correlation assays between epithelial and plasma miR-181b-5p expression and airway eosinophilia were performed. The target of miR-181b-5p, SPP1, was predicted by online algorithms and verified in BEAS-2B cells. The role of miR-181b-5p in epithelial proinflammatory cytokine expression was examined in an in vitro system. RESULTS: Epithelial miR-181b-5p expression was decreased in subjects with asthma. Epithelial miR-181b-5p levels were inversely correlated with sputum and bronchial submucosal eosinophilia. Plasma miR-181b-5p was decreased and correlated with epithelial miR-181b-5p in subjects with asthma. There was a strong inverse correlation between plasma miR-181b-5p and airway eosinophilia in subjects with asthma. Plasma miR-181b-5p was increased after inhaled corticosteroids treatment. We verified that SPP1 is a target of miR-181b-5p. In human bronchial epithelial cells, miR-181b-5p regulated IL-13-induced IL-1beta and CCL11 expression by targeting SPP1. Dexamethasone restored IL-13-induced miR-181b-5p down-regulation and suppressed IL-13-induced SPP1, IL-1beta and CCL11 expression. CONCLUSIONS AND CLINICAL RELEVANCE: Epithelial and plasma miR-181b-5p are potential biomarkers for airway eosinophilia in asthma. MiR-181b-5p may participate in eosinophilic airway inflammation by regulating proinflammatory cytokines expression via targeting SPP1. PMID- 27192553 TI - Prediction of clinical progression after radical prostatectomy in a nationwide population-based cohort. AB - OBJECTIVE: The aim of this study was to create a model for predicting progression free survival after radical prostatectomy for localized prostate cancer. MATERIAL AND METHODS: The risk of biochemical recurrence (BCR) was modelled in a cohort of 3452 men aged 70 years or younger who were primarily treated with radical prostatectomy after being diagnosed between 2003 and 2006 with localized prostate cancer [clinical stage T1c-T2, Gleason score 5-10, N0/NX, M0/MX, prostate specific antigen (PSA) < 20 ng/ml]. The cohort was split into two: one cohort for model development (n = 3452) and one for validation (n = 1762). BCR was defined as two increasing PSA values of at least 0.2 ng/ml, initiation of secondary therapy, distant metastases or death from prostate cancer. Multivariable Cox proportional hazard regression was applied, predictive performance was assessed using the bootstrap resampling technique to calculate the c index, and calibration of the model was evaluated by comparing predicted and observed Kaplan Meier 1 year BCR. RESULTS: The overall 5 year progression-free survival was 83% after a median follow-up time of 6.8 years in the development cohort and 7.3 years in the validation cohort. The final model included T stage, PSA level, primary and secondary Gleason grade, and number of positive and negative biopsies. The c index for discrimination between high and low risk of recurrence was 0.68. The probability of progression-free survival ranged from 22% to 97% over the range of risk scores in the study population. CONCLUSIONS: This model is based on nationwide population-based data and can be used with a fair predictive accuracy to guide decisions on clinical follow-up after prostatectomy. An online calculator for convenient clinical use of the model is available at www.npcr.se/nomogram. PMID- 27192554 TI - Comparison between Timelines of Transcriptional Regulation in Mammals, Birds, and Teleost Fish Somitogenesis. AB - Metameric segmentation of the vertebrate body is established during somitogenesis, when a cyclic spatial pattern of gene expression is created within the mesoderm of the developing embryo. The process involves transcriptional regulation of genes associated with the Wnt, Notch, and Fgf signaling pathways, each gene is expressed at a specific time during the somite cycle. Comparative genomics, including analysis of expression timelines may reveal the underlying regulatory modules and their causal relations, explaining the nature and origin of the segmentation mechanism. Using a deconvolution approach, we computationally reconstruct and compare the precise timelines of expression during somitogenesis in chicken and zebrafish. The result constitutes a resource that may be used for inferring possible causal relations between genes and subsequent pathways. While the sets of regulated genes and expression profiles vary between different species, notable similarities exist between the temporal organization of the pathways involved in the somite clock in chick and mouse, with certain aspects (as the phase of expression of Notch genes) conserved also in the zebrafish. The regulated genes have sequence motifs that are conserved in mouse and chicken but not zebrafish. Promoter sequence analysis suggests involvement of several transcription factors that may bind these regulatory elements, including E2F, EGR and PLAG, as well as a possible role of G-quadruplex DNA structure in regulation of the cyclic genes. Our research lays the groundwork for further studies that will probe the evolution of the regulatory mechanism of segmentation across all vertebrates. PMID- 27192556 TI - The Chlamydia muridarum Organisms Fail to Auto-Inoculate the Mouse Genital Tract after Colonization in the Gastrointestinal Tract for 70 days. AB - Chlamydia muridarum is known to colonize in the gastrointestinal tract for long periods of time, which has been hypothesized to serve as a reservoir for spreading to the genital tract. To test this hypothesis, a luciferase-expressing C. muridarum was used to establish a long-lasting infection in the mouse gastrointestinal tract following either intragastric or intrarectal inoculations. In vivo imaging revealed significant bioluminescent signals mainly in the mouse abdominal area throughout the experiments. Ex vivo imaging localized the signals to the mouse gastrointestinal tract, which was confirmed by monitoring the C. muridarum organisms in the mouse organs/tissues. Despite the long-lasting colonization in the gastrointestinal tract and active shedding of infectious organisms in the rectal swabs, the organisms did not cause any significant infection or pathology in the genital tract throughout the experiments, which was reproduced in multiple strains of mice and with an increased inoculation dose to the gastrointestinal tract. The above observations have demonstrated that the long-lasting C. muridarum organisms from the gastrointestinal tract are inefficient in auto-inoculating the genital tract, suggesting that the gastrointestinal tract Chlamydia may utilize an indirect mechanism to affect its pathogenicity in the genital tract. PMID- 27192557 TI - Microsatellite allele sizes alone are insufficient to delineate species boundaries in Symbiodinium. AB - Symbiodinium are a diverse group of unicellular dinoflagellates that are important nutritional symbionts of reef-building corals. Symbiodinium putative species ('types') are commonly identified with genetic markers, mostly nuclear and chloroplast encoded ribosomal DNA regions. Population genetic analyses using microsatellite loci have provided insights into Symbiodinium biogeography, connectivity and phenotypic plasticity, but are complicated by: (i) a lack of consensus criteria used to delineate inter- vs. intragenomic variation within species; and (ii) the high density of Symbiodinium in host tissues, which results in single samples comprising thousands of individuals. To address this problem, Wham & LaJeunesse (2016) present a method for identifying cryptic Symbiodinium species from microsatellite data based on correlations between allele size distributions and nongeographic genetic structure. Multilocus genotypes that potentially do not recombine in sympatry are interpreted as secondary 'species' to be discarded from downstream population genetic analyses. However, Symbiodinium species delineations should ideally incorporate multiple physiological, ecological and molecular criteria. This is because recombination tests may be a poor indicator of species boundaries in Symbiodinium due to their predominantly asexual mode of reproduction. Furthermore, discontinuous microsatellite allele sizes in sympatry may be explained by secondary contact between previously isolated populations and by mutations that occur in a nonstepwise manner. Limitations of using microsatellites alone to delineate species are highlighted in earlier studies that demonstrate occasional bimodal distributions of allele sizes within Symbiodinium species and considerable allele size sharing among Symbiodinium species. We outline these issues and discuss the validity of reinterpretations of our previously published microsatellite data from Symbiodinium populations on the Great Barrier Reef (Howells et al. 2013). PMID- 27192558 TI - Promoting Physical Activity With Group Pictures. Affiliation-Based Visual Communication for High-Risk Populations. AB - Past research in social and health psychology has shown that affiliation motivation is associated with health behavior, especially for high-risk populations, suggesting that targeting this motivation could be a promising strategy to promote physical activity. However, the effects that affiliation appeals (e.g., pictures depicting companionship during physical activities) and accompanying slogans have on motivating physical activity have been largely unexplored. Hence, our two studies experimentally tested the effects of exposure to affiliation-based pictures for overweight or less active people, as well as the moderating effect of affiliation motivation. The results of these two studies give some indication that group pictures (with or without an accompanying slogan) can be an effective strategy to improve high-risk populations' attitudes, self efficacy, and intentions to engage in physical activity. Affiliation motivation as a personality trait did not interact with these effects, but was positively associated with attitudes, independent of the group picture effect. PMID- 27192555 TI - Development and evaluation of a host-targeted antiviral that abrogates herpes simplex virus replication through modulation of arginine-associated metabolic pathways. AB - Since their inception five decades ago, most antivirals have been engineered to disrupt a single viral protein or process that is essential for viral replication. This approach has limited the overall therapeutic effectiveness and applicability of current antivirals due to restricted viral specificity, a propensity for development of drug resistance, and an inability to control deleterious host-mediated inflammation. As obligate intracellular parasites, viruses are reliant on host metabolism and macromolecular synthesis pathways. Of these biosynthetic processes, many viruses, including Herpes simplex viruses (HSV), are absolutely dependent on the bioavailability of arginine, a non essential amino acid that is critical for many physiological and pathophysiological processes associated with either facilitating viral replication or progression of disease. To assess if targeting host arginine associated metabolic pathways would inhibit HSV replication, a pegylated recombinant human Arginase I (peg-ArgI) was generated and its in vitro anti herpetic activity was evaluated. Cells continuously treated with peg-ArgI for over 48 h exhibited no signs of cytotoxicity or loss of cell viability. The antiviral activity of peg-ArgI displayed a classical dose-response curve with IC50's in the sub-nanomolar range. peg-ArgI potently inhibited HSV-1 and HSV-2 viral replication, infectious virus production, cell-to-cell spread/transmission and virus-mediated cytopathic effects. Not unexpectedly given its host-targeted mechanism of action, peg-ArgI showed similar effectiveness at controlling replication of single and multidrug resistant HSV-1 mutants. These findings illustrate that targeting host arginine-associated metabolic pathways is an effective means of controlling viral replicative processes. Further exploration into the breadth of viruses inhibited by peg-ArgI, as well as the ability of peg ArgI to suppress arginine-associated virus-mediated pathophysiological disease processes is warranted. PMID- 27192559 TI - Effects of dietary protein and energy levels on digestive enzyme activities and electrolyte composition in the small intestinal fluid of geese. AB - The present study was conducted to evaluate the effects of dietary protein and energy levels on digestive enzymes and electrolyte composition in jejunum of geese. A 3*3 factorial and completely randomized design was adopted with three protein levels and three energy levels. The experiment included four replicates for each treatment, and three geese for each replicate. Isovolumetric supernate from centrifugal jejuna fluid were mixed in each replicate. Activities of digestive enzymes and ions were analyzed. The results showed trypsin and chymotrypsin activities were significantly increased with increasing of dietary protein and energy levels (P<0.05). The concentrations of Ca2+ and pH value were significantly decreased by increased dietary protein and energy levels. However, no significant differences were found for the activities of amylase and cellulase, as well as the concentration of Na+ among groups with different protein and energy levels. In conclusion, digesta enzymes and electrolytes in the small intestine adapted to the protein and energy levels. The activities of protease, rather than amylase and cellulase were induced with increasing of protein and energy levels. The imbalance of positive and negative ions was possibly adjusted by the fluctuant concentrations of K+ , Cl- and Ca2+ for maintaining normal physiological function. PMID- 27192560 TI - Neurophysiological Correlates of Musical and Prosodic Phrasing: Shared Processing Mechanisms and Effects of Musical Expertise. AB - The processing of prosodic phrase boundaries in language is immediately reflected by a specific event-related potential component called the Closure Positive Shift (CPS). A component somewhat reminiscent of the CPS in language has also been reported for musical phrases (i.e., the so-called 'music CPS'). However, in previous studies the quantification of the music-CPS as well as its morphology and timing differed substantially from the characteristics of the language-CPS. Therefore, the degree of correspondence between cognitive mechanisms of phrasing in music and in language has remained questionable. Here, we probed the shared nature of mechanisms underlying musical and prosodic phrasing by (1) investigating whether the music-CPS is present at phrase boundary positions where the language-CPS has been originally reported (i.e., at the onset of the pause between phrases), and (2) comparing the CPS in music and in language in non musicians and professional musicians. For the first time, we report a positive shift at the onset of musical phrase boundaries that strongly resembles the language-CPS and argue that the post-boundary 'music-CPS' of previous studies may be an entirely distinct ERP component. Moreover, the language-CPS in musicians was found to be less prominent than in non-musicians, suggesting more efficient processing of prosodic phrases in language as a result of higher musical expertise. PMID- 27192561 TI - Multipotent neurogenic fate of mesenchymal stem cell is determined by Cdk4 mediated hypophosphorylation of Smad-STAT3. AB - Cyclin-dependent kinase (Cdk) in complex with a corresponding cyclin plays a pivotal role in neurogenic differentiation. In particular, Cdk4 activity acts as a signaling switch to direct human mesenchymal stem cells (MSCs) to neural transdifferentiation. However, the molecular evidence of how Cdk4 activity converts MSCs to neurogenic lineage remains unknown. Here, we found that Cdk4 inhibition in human MSCs enriches the populations of neural stem and progenitor pools rather than differentiated glial and neuronal cell pools. Interestingly, Cdk4 inhibition directly inactivates Smads and subsequently STAT3 signaling by hypophosphorylation, and both Cdk4 and Smads levels are linked during the processes of neural transdifferentiation and differentiation. In summary, our results provide novel molecular evidence in which Cdk4 inhibition leads to directing human MSCs to a multipotent neurogenic fate by inactivating Smads-STAT3 signaling. PMID- 27192562 TI - Cellulose Structural Polymorphism in Plant Primary Cell Walls Investigated by High-Field 2D Solid-State NMR Spectroscopy and Density Functional Theory Calculations. AB - The native cellulose of bacterial, algal, and animal origins has been well studied structurally using X-ray and neutron diffraction and solid-state NMR spectroscopy, and is known to consist of varying proportions of two allomorphs, Ialpha and Ibeta, which differ in hydrogen bonding, chain packing, and local conformation. In comparison, cellulose structure in plant primary cell walls is much less understood because plant cellulose has lower crystallinity and extensive interactions with matrix polysaccharides. Here we have combined two dimensional magic-angle-spinning (MAS) solid-state nuclear magnetic resonance (solid-state NMR) spectroscopy at high magnetic fields with density functional theory (DFT) calculations to obtain detailed information about the structural polymorphism and spatial distributions of plant primary-wall cellulose. 2D (13)C (13)C correlation spectra of uniformly (13)C-labeled cell walls of several model plants resolved seven sets of cellulose chemical shifts. Among these, five sets (denoted a-e) belong to cellulose in the interior of the microfibril while two sets (f and g) can be assigned to surface cellulose. Importantly, most of the interior cellulose (13)C chemical shifts differ significantly from the (13)C chemical shifts of the Ialpha and Ibeta allomorphs, indicating that plant primary wall cellulose has different conformations, packing, and hydrogen bonding from celluloses of other organisms. 2D (13)C-(13)C correlation experiments with long mixing times and with water polarization transfer revealed the spatial distributions and matrix-polysaccharide interactions of these cellulose structures. Celluloses f and g are well mixed chains on the microfibril surface, celluloses a and b are interior chains that are in molecular contact with the surface chains, while cellulose c resides in the core of the microfibril, outside spin diffusion contact with the surface. Interestingly, cellulose d, whose chemical shifts differ most significantly from those of bacterial, algal, and animal cellulose, interacts with hemicellulose, is poorly hydrated, and is targeted by the protein expansin during wall loosening. To obtain information about the C6 hydroxymethyl conformation of these plant celluloses, we carried out DFT calculations of (13)C chemical shifts, using the Ialpha and Ibeta crystal structures as templates and varying the C5-C6 torsion angle. Comparison with the experimental chemical shifts suggests that all interior cellulose favor the tg conformation, but cellulose d also has a similar propensity to adopt the gt conformation. These results indicate that cellulose in plant primary cell walls, due to their interactions with matrix polysaccharides, and has polymorphic structures that are not a simple superposition of the Ialpha and Ibeta allomorphs, thus distinguishing them from bacterial and animal celluloses. PMID- 27192563 TI - Coinhibitory Pathways in the B7-CD28 Ligand-Receptor Family. AB - Immune responses need to be controlled for optimal protective immunity and tolerance. Coinhibitory pathways in the B7-CD28 family provide critical inhibitory signals that regulate immune homeostasis and defense and protect tissue integrity. These coinhibitory signals limit the strength and duration of immune responses, thereby curbing immune-mediated tissue damage, regulating resolution of inflammation, and maintaining tolerance to prevent autoimmunity. Tumors and microbes that cause chronic infections can exploit these coinhibitory pathways to establish an immunosuppressive microenvironment, hindering their eradication. Advances in understanding T cell coinhibitory pathways have stimulated a new era of immunotherapy with effective drugs to treat cancer, autoimmune and infectious diseases, and transplant rejection. In this review we discuss the current knowledge of the mechanisms underlying the coinhibitory functions of pathways in the B7-CD28 family, the diverse functional consequences of these inhibitory signals on immune responses, and the overlapping and unique functions of these key immunoregulatory pathways. PMID- 27192565 TI - Lag-3, Tim-3, and TIGIT: Co-inhibitory Receptors with Specialized Functions in Immune Regulation. AB - Co-inhibitory receptors, such as CTLA-4 and PD-1, have an important role in regulating T cell responses and have proven to be effective targets in the setting of chronic diseases where constitutive co-inhibitory receptor expression on T cells dampens effector T cell responses. Unfortunately, many patients still fail to respond to therapies that target CTLA-4 and PD-1. The next wave of co inhibitory receptor targets that are being explored in clinical trials include Lag-3, Tim-3, and TIGIT. These receptors, although they belong to the same class of receptors as PD-1 and CTLA-4, exhibit unique functions, especially at tissue sites where they regulate distinct aspects of immunity. Increased understanding of the specialized functions of these receptors will inform the rational application of therapies that target these receptors to the clinic. PMID- 27192564 TI - CD28 Costimulation: From Mechanism to Therapy. AB - Ligation of the CD28 receptor on T cells provides a critical second signal alongside T cell receptor (TCR) ligation for naive T cell activation. Here, we discuss the expression, structure, and biochemistry of CD28 and its ligands. CD28 signals play a key role in many T cell processes, including cytoskeletal remodeling, production of cytokines, survival, and differentiation. CD28 ligation leads to unique epigenetic, transcriptional, and post-translational changes in T cells that cannot be recapitulated by TCR ligation alone. We discuss the function of CD28 and its ligands in both effector and regulatory T cells. CD28 is critical for regulatory T cell survival and the maintenance of immune homeostasis. We outline the roles that CD28 and its family members play in human disease and we review the clinical efficacy of drugs that block CD28 ligands. Despite the centrality of CD28 and its family members and ligands to immune function, many aspects of CD28 biology remain unclear. Translation of a basic understanding of CD28 function into immunomodulatory therapeutics has been uneven, with both successes and failures. Such real-world results might stem from multiple factors, including complex receptor-ligand interactions among CD28 family members, differences between the mouse and human CD28 families, and cell-type specific roles of CD28 family members. PMID- 27192567 TI - T Cell Cosignaling Molecules in Transplantation. AB - The ultimate outcome of alloreactivity versus tolerance following transplantation is potently influenced by the constellation of cosignaling molecules expressed by immune cells during priming with alloantigen, and the net sum of costimulatory and coinhibitory signals transmitted via ligation of these molecules. Intense investigation over the last two decades has yielded a detailed understanding of the kinetics, cellular distribution, and intracellular signaling networks of cosignaling molecules such as the CD28, TNF, and TIM families of receptors in alloimmunity. More recent work has better defined the cellular and molecular mechanisms by which engagement of cosignaling networks serve to either dampen or augment alloimmunity. These findings will likely aid in the rational development of novel immunomodulatory strategies to prolong graft survival and improve outcomes following transplantation. PMID- 27192571 TI - Regulatory T Cells: A Crisis Averted. AB - Although regulatory T cells protect people from autoimmunity, two recent papers in Immunity (Malchow et al., 2016; Kieback et al., 2016) demonstrate that these cells are also a crisis averted. Without the proper education in the thymus, these cells will turn on their host and cause autoimmunity. PMID- 27192570 TI - Targeting T Cell Co-receptors for Cancer Therapy. AB - Checkpoint-blocking antibodies can generate potent anti-tumor responses by encouraging the immune system to seek and destroy cancer cells. At this time, the United States Food and Drug Administration has approved three checkpoint-blocking antibodies in three disease indications, and additional approvals are expected to broaden the clinical scope of immunotherapy. Herein, we review the clinical development of CTLA-4-, PD-1-, and PD-L1-blocking antibodies across tumor types and briefly discuss areas of active investigation of potential biomarkers. PMID- 27192572 TI - Making Ends Meet: Myeloid Cells Catalyze Blood Vessel Repair in the Brain. AB - Hemorrhagic stroke, primarily caused by rupture of blood vessels in the brain, is a leading cause of death and disability in adults. In this issue of Immunity, Liu et al. (2016) demonstrate that repair of cerebrovascular ruptures can be directly mediated by myeloid cells. PMID- 27192566 TI - The TNF Receptor Superfamily in Co-stimulating and Co-inhibitory Responses. AB - Cytokines related to tumor necrosis factor (TNF) provide a communication network essential for coordinating multiple cell types into an effective host defense system against pathogens and malignant cells. The pathways controlled by the TNF superfamily differentiate both innate and adaptive immune cells and modulate stromal cells into microenvironments conducive to host defenses. Members of the TNF receptor superfamily activate diverse cellular functions from the production of type 1 interferons to the modulation of survival of antigen-activated T cells. Here, we focus attention on the subset of TNF superfamily receptors encoded in the immune response locus in chromosomal region 1p36. Recent studies have revealed that these receptors use diverse mechanisms to either co-stimulate or restrict immune responses. Translation of the fundamental mechanisms of TNF superfamily is leading to the design of therapeutics that can alter pathogenic processes in several autoimmune diseases or promote immunity to tumors. PMID- 27192568 TI - Co-stimulatory and Co-inhibitory Pathways in Autoimmunity. AB - The immune system is guided by a series of checks and balances, a major component of which is a large array of co-stimulatory and co-inhibitory pathways that modulate the host response. Although co-stimulation is essential for boosting and shaping the initial response following signaling through the antigen receptor, inhibitory pathways are also critical for modulating the immune response. Excessive co-stimulation and/or insufficient co-inhibition can lead to a breakdown of self-tolerance and thus to autoimmunity. In this review, we will focus on the role of co-stimulatory and co-inhibitory pathways in two systemic (systemic lupus erythematosus and rheumatoid arthritis) and two organ-specific (multiple sclerosis and type 1 diabetes) emblematic autoimmune diseases. We will also discuss how mechanistic analysis of these pathways has led to the identification of potential therapeutic targets and initiation of clinical trials for autoimmune diseases, as well as outline some of the challenges that lie ahead. PMID- 27192573 TI - Homing in on the Sweet Side of Immune Checkpoint Biology. AB - P-selectin glycoprotein ligand-1 (PSGL-1) and its glycostructural determinants facilitate responses to infection and cancer by promoting immune effector-cell trafficking into inflamed tissue. In this issue of Immunity, Tinoco et al. (2016) report homing-independent functions of PSGL-1 in immune checkpoint regulation and T cell effector activity, in models of chronic viral infection and melanoma. PMID- 27192569 TI - Costimulatory and Coinhibitory Receptor Pathways in Infectious Disease. AB - Costimulatory and inhibitory receptors play a key role in regulating immune responses to infections. Recent translation of knowledge about inhibitory receptors such as CTLA-4 and PD-1 into the cancer clinic highlights the opportunities to manipulate these pathways to treat human disease. Studies in infectious disease have provided key insights into the specific roles of these pathways and the effects of their manipulation. Here, recent studies are discussed that have addressed how major inhibitory and costimulatory pathways play a role in regulating immune responses during acute and chronic infections. Mechanistic insights from studies of infectious disease provide opportunities to further expand our toolkit to treat cancer and chronic infections in the clinic. PMID- 27192574 TI - Offspring's Tolerance of Mother Goes Viral. AB - Pregnancy uniquely allows genetically discordant tissues of the mother and child to intimately coexist in harmony. In this issue of Immunity, Ou and colleagues show that hepatitis B virus exploits these naturally occurring immune tolerance pathways to establish persistent postnatal infection in offspring. PMID- 27192575 TI - HIV Immunology Goes Out On a Limb. AB - Vaccines against HIV most likely need to elicit broadly neutralizing antibodies. In this issue of Immunity, Poignard and colleagues describe the co-evolution of a broadly neutralizing antibody and the virus that triggered it, providing a template for HIV vaccine design. PMID- 27192576 TI - A Cholesterol-Based Allostery Model of T Cell Receptor Phosphorylation. AB - Signaling through the T cell receptor (TCR) controls adaptive immune responses. Antigen binding to TCRalphabeta transmits signals through the plasma membrane to induce phosphorylation of the CD3 cytoplasmic tails by incompletely understood mechanisms. Here we show that cholesterol bound to the TCRbeta transmembrane region keeps the TCR in a resting, inactive conformation that cannot be phosphorylated by active kinases. Only TCRs that spontaneously detached from cholesterol could switch to the active conformation (termed primed TCRs) and then be phosphorylated. Indeed, by modulating cholesterol binding genetically or enzymatically, we could switch the TCR between the resting and primed states. The active conformation was stabilized by binding to peptide-MHC, which thus controlled TCR signaling. These data are explained by a model of reciprocal allosteric regulation of TCR phosphorylation by cholesterol and ligand binding. Our results provide both a molecular mechanism and a conceptual framework for how lipid-receptor interactions regulate signal transduction. PMID- 27192577 TI - Thymus-Derived Regulatory T Cells Are Positively Selected on Natural Self-Antigen through Cognate Interactions of High Functional Avidity. AB - Regulatory T (Treg) cells expressing Foxp3 transcripton factor are essential for immune homeostasis. They arise in the thymus as a separate lineage from conventional CD4(+)Foxp3(-) T (Tconv) cells. Here, we show that the thymic development of Treg cells depends on the expression of their endogenous cognate self-antigen. The formation of these cells was impaired in mice lacking this self antigen, while Tconv cell development was not negatively affected. Thymus-derived Treg cells were selected by self-antigens in a specific manner, while autoreactive Tconv cells were produced through degenerate recognition of distinct antigens. These distinct modes of development were associated with the expression of T cell receptor of higher functional avidity for self-antigen by Treg cells than Tconv cells, a difference subsequently essential for the control of autoimmunity. Our study documents how self-antigens define the repertoire of thymus-derived Treg cells to subsequently endow this cell type with the capacity to undermine autoimmune attack. PMID- 27192578 TI - PSGL-1 Is an Immune Checkpoint Regulator that Promotes T Cell Exhaustion. AB - Chronic viruses and cancers thwart immune responses in humans by inducing T cell dysfunction. Using a murine chronic virus that models human infections, we investigated the function of the adhesion molecule, P-selectin glycoprotein ligand-1 (PSGL-1), that is upregulated on responding T cells. PSGL-1-deficient mice cleared the virus due to increased intrinsic survival of multifunctional effector T cells that had downregulated PD-1 as well as other inhibitory receptors. Notably, this response resulted in CD4(+)-T-cell-dependent immunopathology. Mechanistically, PSGL-1 ligation on exhausted CD8(+) T cells inhibited T cell receptor (TCR) and interleukin-2 (IL-2) signaling and upregulated PD-1, leading to diminished survival with TCR stimulation. In models of melanoma cancer in which T cell dysfunction occurs, PSGL-1 deficiency led to PD-1 downregulation, improved T cell responses, and tumor control. Thus, PSGL-1 plays a fundamental role in balancing viral control and immunopathology and also functions to regulate T cell responses in the tumor microenvironment. PMID- 27192581 TI - Visceral leishmaniasis in Southern Rio de Janeiro State and the risk of propagation to Sao Paulo State, Brazil. PMID- 27192580 TI - A simple method for assessing occupational exposure via the one-way random effects model. AB - A one-way random effects model is postulated for the log-transformed shift-long personal exposure measurements, where the random effect in the model represents an effect due to the worker. Simple closed-form confidence intervals are proposed for the relevant parameters of interest using the method of variance estimates recovery (MOVER). The performance of the confidence bounds is evaluated and compared with those based on the generalized confidence interval approach. Comparison studies indicate that the proposed MOVER confidence bounds are better than the generalized confidence bounds for the overall mean exposure and an upper percentile of the exposure distribution. The proposed methods are illustrated using a few examples involving industrial hygiene data. PMID- 27192582 TI - Epstein-Barr virus-positive gastric cancer: a distinct molecular subtype of the disease? AB - Approximately 90% of the world population is infected by Epstein-Barr virus (EBV). Usually, it infects B lymphocytes, predisposing them to malignant transformation. Infection of epithelial cells occurs rarely, and it is estimated that about to 10% of gastric cancer patients harbor EBV in their malignant cells. Given that gastric cancer is the third leading cause of cancer-related mortality worldwide, with a global annual incidence of over 950,000 cases, EBV-positive gastric cancer is the largest group of EBV-associated malignancies. Based on gene expression profile studies, gastric cancer was recently categorized into four subtypes; EBV-positive, microsatellite unstable, genomically stable and chromosomal instability. Together with previous studies, this report provided a more detailed molecular characterization of gastric cancer, demonstrating that EBV-positive gastric cancer is a distinct molecular subtype of the disease, with unique genetic and epigenetic abnormalities, reflected in a specific phenotype. The recognition of characteristic molecular alterations in gastric cancer allows the identification of molecular pathways involved in cell proliferation and survival, with the potential to identify therapeutic targets. These findings highlight the enormous heterogeneity of gastric cancer, and the complex interplay between genetic and epigenetic alterations in the disease, and provide a roadmap to implementation of genome-guided personalized therapy in gastric cancer. The present review discusses the initial studies describing EBV-positive gastric cancer as a distinct clinical entity, presents recently described genetic and epigenetic alterations, and considers potential therapeutic insights derived from the recognition of this new molecular subtype of gastric adenocarcinoma. PMID- 27192584 TI - Over expression of AdeABC and AcrAB-TolC efflux systems confers tigecycline resistance in clinical isolates of Acinetobacter baumannii and Klebsiella pneumoniae. AB - INTRODUCTION: Due to the wide use of tigecycline in the treatment of severe infections caused by multidrug-resistant (MDR) bacteria, clinical resistance to tigecycline has increased in recent years. Here, we investigated the relationship between tigecycline resistance and the expression of efflux pumps. METHODS: Clinical isolates of Acinetobacter baumannii and Klebsiella pneumoniae were consecutively collected from hospitalized patients in three hospitals. The minimum inhibitory concentration (MIC) of tigecycline was determined using the broth microdilution method. Expression levels of efflux pump genes and regulators were examined by quantitative real-time reverse transcription polymerase chain reaction. The correlations between tigecycline MICs and gene expression levels were analyzed. RESULTS: Overall, 1,026 A. baumannii and 725 K. pneumoniae strains were collected. Most strains were isolated from sputum. The tigecycline resistance rate was 13.4% in A. baumannii isolates and 6.5% in K. pneumoniae isolates. Overexpression of AdeABC and AcrAB-TolC efflux systems was observed found in clinical tigecycline-resistant isolates. The tigecycline MIC had a linear relationship with the adeB expression level in A. baumannii isolates, but not with the acrB expression level in K. pneumoniae isolates. There were significant linear trends in the overexpression of ramA as the tigecycline MIC increased in K. pneumoniae isolates. CONCLUSIONS: Tigecycline resistance in A. baumannii and K. pneumoniae was strongly associated with the overexpression of efflux systems. More studies are needed to elucidate whether there are other regulators that affect the expression of adeB in A. baumannii and how ramA affects the expression of acrB in K. pneumoniae. PMID- 27192583 TI - Integrative literature review of the reported uses of serological tests in leprosy management. AB - An integrative literature review was conducted to synthesize available publications regarding the potential use of serological tests in leprosy programs. We searched the databases Literatura Latino-Americana e do Caribe em Ciencias da Saude, Indice Bibliografico Espanhol em Ciencias da Saude, Acervo da Biblioteca da Organizacao Pan-Americana da Saude, Medical Literature Analysis and Retrieval System Online, Hanseniase, National Library of Medicine, Scopus, Ovid, Cinahl, and Web of Science for articles investigating the use of serological tests for antibodies against phenolic glycolipid-I (PGL-I), ML0405, ML2331, leprosy IDRI diagnostic-1 (LID-1), and natural disaccharide octyl-leprosy IDRI diagnostic-1 (NDO-LID). From an initial pool of 3.514 articles, 40 full-length articles fulfilled our inclusion criteria. Based on these papers, we concluded that these antibodies can be used to assist in diagnosing leprosy, detecting neuritis, monitoring therapeutic efficacy, and monitoring household contacts or at-risk populations in leprosy-endemic areas. Thus, available data suggest that serological tests could contribute substantially to leprosy management. PMID- 27192585 TI - Monoterpene isolated from the essential oil of Trachyspermum ammi is cytotoxic to multidrug-resistant Pseudomonas aeruginosa and Staphylococcus aureus strains. AB - INTRODUCTION: The aim of this study was to determine whether an herbal extract containing monoterpene exhibited activity against multidrug-resistant Staphylococcus aureus and Pseudomonas aeruginosa isolated from clinical infection samples. METHODS: The essential oil of Trachyspermum ammi (L.) Sprague ex Turrill (Apiaceae) fruit was extracted by hydrodistillation. Fruit residues were treated with hydrochloric acid and re-hydrodistilled to obtain volatile compounds. Compounds in the distilled oil were identified using gas-chromatography (GC) and GC-mass spectrometry (MS). The antibiotic susceptibility of all bacterial isolates was analyzed using both the disc diffusion method and determination of the minimum inhibitory concentration (MIC). The sensitivity of antibiotic resistant isolates to essential oil was also determined by using the disc diffusion method and MIC determination. RESULTS: Of 26 clinical isolates, 92% were multidrug-resistant (MDR). Aromatic monoterpenes (thymol, paracymene, and gamma-terpinene) were the major (90%) components of the oil. Growth of S. aureus strains was successfully inhibited by the oil, with an inhibitory zone diameter (IZD) between 30-60mm and MIC <0.02MUL/mL. The oil had no antimicrobial activity against clinical isolates of P. aeruginosa; rather, it prevented pigment production in these isolates. CONCLUSIONS: This study revealed that the essential oil of Trachyspermum ammi, which contains monoterpene, has good antibacterial potency. Monoterpenes could thus be incorporated into antimicrobial ointment formulas in order to treat highly drug-resistant S. aureus infections. Our findings also underscore the utility of research on natural products in order to combat bacterial multidrug resistance. PMID- 27192586 TI - Secular trends in Klebsiella pneumoniae isolated in a tertiary-care hospital: increasing prevalence and accelerated decline in antimicrobial susceptibility. AB - INTRODUCTION Klebsiella pneumoniae has become an increasingly important etiologic agent of nosocomial infections in recent years. This is mainly due to the expression of virulence factors and development of resistance to several antimicrobial drugs. METHODS This retrospective study examines data obtained from the microbiology laboratory of a Brazilian tertiary-care hospital. To assess temporal trends in prevalence and antimicrobial susceptibility, K. pneumoniae isolates were analyzed from 2000 to 2013. The relative frequencies of K. pneumoniae isolation were calculated among all Gram-negative bacilli isolated in each period analyzed. Susceptibility tests were performed using automated systems. RESULTS: From 2000-2006, K. pneumonia isolates comprised 10.7% of isolated Gram-negative bacilli (455/4260). From 2007-2013, this percentage was 18.1% (965/5331). Strictly considering isolates from bloodstream infections, the relative annual prevalence of K. pneumoniae increased from 14-17% to 27-32% during the same periods. A progressive decrease in K. pneumoniae susceptibility to all antimicrobial agents assessed was detected. Partial resistance was also observed to antimicrobial drugs that have been used more recently, such as colistin and tigecycline. CONCLUSIONS Our study indicates that K. pneumoniae has become a major pathogen among hospitalized patients and confirms its recent trend of increasing antimicrobial resistance. PMID- 27192579 TI - Early Antibody Lineage Diversification and Independent Limb Maturation Lead to Broad HIV-1 Neutralization Targeting the Env High-Mannose Patch. AB - The high-mannose patch on HIV Env is a preferred target for broadly neutralizing antibodies (bnAbs), but to date, no vaccination regimen has elicited bnAbs against this region. Here, we present the development of a bnAb lineage targeting the high-mannose patch in an HIV-1 subtype-C-infected donor from sub-Saharan Africa. The Abs first acquired autologous neutralization, then gradually matured to achieve breadth. One Ab neutralized >47% of HIV-1 strains with only ~11% somatic hypermutation and no insertions or deletions. By sequencing autologous env, we determined key residues that triggered the lineage and participated in Ab Env coevolution. Next-generation sequencing of the Ab repertoire showed an early expansive diversification of the lineage followed by independent maturation of individual limbs, several of them developing notable breadth and potency. Overall, the findings are encouraging from a vaccine standpoint and suggest immunization strategies mimicking the evolution of the entire high-mannose patch and promoting maturation of multiple diverse Ab pathways. PMID- 27192587 TI - Trypanosoma cruzi isolated from a triatomine found in one of the biggest metropolitan areas of Latin America. AB - INTRODUCTION: To characterize Trypanosoma cruzi (TcI) isolated from a Panstrongylus megistus specimen found in one of the biggest metropolitan areas of Latin America, the relationship between the TcI group of T. cruzi and the transmission cycle in the urban environment was studied. METHODS: The T. cruzi strain, Pm, was isolated in a culture medium from the evolutionary forms present in the hindgut of a live male specimen of P. megistus found in the Jabaquara subway in Sao Paulo City. The sample from the triatomine showed trypomastigote forms of Trypanosomatidae, which were inoculated in the peritoneum of Balb/c mice. The sample was then inoculated in Liver Infusion Tryptose medium and J774 cells for the molecular identification and characterization of the parasite. The Pm strain of T. cruzi was identified by isolation in axenic culture medium, and based on the morphology, cell infection, growth kinetics, and molecular characterization. RESULTS: After isolation, the protozoan was identified as T. cruzi. No parasites were detected in the peripheral blood of the animal, which can be a characteristic inherent to the strain of T. cruzi that was isolated. Cell invasion assays were performed in triplicate in the J774 cell line to confirm the invasive ability of the Pm strain and revealed amastigote forms of the parasite within macrophages. CONCLUSIONS: Our biological and molecular characterizations helped understand parasite-host interactions and their evolutionary history in context of the associations between vectors, ecotopes, hosts, and groups of the parasite. PMID- 27192588 TI - Extraction of Trypanosoma cruzi DNA from food: a contribution to the elucidation of acute Chagas disease outbreaks. AB - INTRODUCTION: Before 2004, the occurrence of acute Chagas disease (ACD) by oral transmission associated with food was scarcely known or investigated. Originally sporadic and circumstantial, ACD occurrences have now become frequent in the Amazon region, with recently related outbreaks spreading to several Brazilian states. These cases are associated with the consumption of acai juice by waste reservoir animals or insect vectors infected with Trypanosoma cruzi in endemic areas. Although guidelines for processing the fruit to minimize contamination through microorganisms and parasites exist, acai-based products must be assessed for quality, for which the demand for appropriate methodologies must be met. METHODS: Dilutions ranging from 5 to 1,000 T. cruzi CL Brener cells were mixed with 2mL of acai juice. Four Extraction of T. cruzi DNA methods were used on the fruit, and the cetyltrimethyl ammonium bromide (CTAB) method was selected according to JRC, 2005. RESULTS: DNA extraction by the CTAB method yielded satisfactory results with regard to purity and concentration for use in PCR. Overall, the methods employed proved that not only extraction efficiency but also high sensitivity in amplification was important. CONCLUSIONS: The method for T. cruzi detection in food is a powerful tool in the epidemiological investigation of outbreaks as it turns epidemiological evidence into supporting data that serve to confirm T. cruzi infection in the foods. It also facilitates food quality control and assessment of good manufacturing practices involving acai-based products. PMID- 27192589 TI - Antimonial drugs entrapped into phosphatidylserine liposomes: physicochemical evaluation and antileishmanial activity. AB - INTRODUCTION: Leishmaniasis is a disease caused by the protozoan Leishmania that resides mainly in mononuclear phagocytic system tissues. Pentavalent antimonials are the main treatment option, although these drugs have toxic side effects and high resistance rates. A potentially alternative and more effective therapeutic strategy is to use liposomes as carriers of the antileishmanial agents. The aims of this study were to develop antimonial drugs entrapped into phosphatidylserine liposomes and to analyze their biological and physicochemical characteristics. METHODS: Liposomes containing meglumine antimoniate (MA) or pentavalent antimony salt (Sb) were obtained through filter extrusion (FEL) and characterized by transmission electron microscopy. Promastigotes of Leishmania infantum were incubated with the drugs and the viability was determined with a tetrazolium dye (MTT assay). The effects of these drugs against intracellular amastigotes were also evaluated by optical microscopy, and mammalian cytotoxicity was determined by an MTT assay. RESULTS: Liposomes had an average diameter of 162nm. MA-FEL showed inhibitory activity against intracellular L. infantum amastigotes, with a 50% inhibitory concentration (IC50) of 0.9MUg/mL, whereas that of MA was 60MUg/mL. Sb-FEL showed an IC50 value of 0.2MUg/mL, whereas that of free Sb was 9MUg/mL. MA-FEL and Sb-FEL had strong in vitro activity that was 63-fold and 39 fold more effective than their respective free drugs. MA-FEL tested at a ten times higher concentration than Sb-FEL did not show cytotoxicity to mammalian cells, resulting in a higher selectivity index. CONCLUSIONS: Antimonial drug containing liposomes are more effective against Leishmania-infected macrophages than the non-liposomal drugs. PMID- 27192590 TI - Molecular characterization of Mycobacterium tuberculosis isolates from Tehran, Iran by restriction fragment length polymorphism analysis and spoligotyping. AB - INTRODUCTION Characterization of Mycobacterium tuberculosis (MTB) isolates by DNA fingerprinting has contributed to tuberculosis (TB) control. The aim of this study was to determine the genetic diversity of MTB isolates from Tehran province in Iran. METHODS MTB isolates from 60 Iranian and 10 Afghan TB patients were fingerprinted by standard IS6110-restriction fragment length polymorphism (RFLP) analysis and spoligotyping. RESULTS The copy number of IS6110 ranged from 10-24 per isolate. The isolates were classified into 22 clusters showing >= 80% similarity by RFLP analysis. Fourteen multidrug-resistant (MDR) isolates were grouped into 4 IS6110-RFLP clusters, with 10 isolates [71% (95% CI: 45-89%)] in 1 cluster, suggesting a possible epidemiological linkage. Eighteen Iranian isolates showed >= 80% similarity with Afghan isolates. There were no strains with identical fingerprints. Spoligotyping of 70 isolates produced 23 distinct patterns. Sixty (85.7%) isolates were grouped into 13 clusters, while the remaining 10 isolates (14.2%) were not clustered. Ural (formerly Haarlem4) (n = 22, 31.4%) was the most common family followed by Central Asian strain (CAS) (n = 18, 25.7%) and T (n = 9, 12.8%) families. Only 1strain was characterized as having the Beijing genotype. Among 60 Iranian and 10 Afghan MTB isolates, 25% (95% CI: 16-37) and 70% (95% CI: 39-89) were categorized as Ural lineage, respectively. CONCLUSIONS A higher prevalence of Ural family MTB isolates among Afghan patients than among Iranian patients suggests the possible transmission of this lineage following the immigration of Afghans to Iran. PMID- 27192591 TI - Two decades of tuberculosis in a city in Northeastern Brazil: advances and challenges in time and space. AB - INTRODUCTION This study presents two decades of epidemiological data on tuberculosis (TB), in order to understanding the disease profile and its spatiotemporal dynamics. METHODS This descriptive study was performed in the City of Olinda/Pernambuco, Brazil, from 1991-2010, and it analyzed new patients with TB living in the city. We used the chi2-test with a p-value <0.05 to identify differences in trends. Incidence and cluster distribution were identified using spatial scan statistics. RESULTS In total, 6202 new cases were recorded during the two decades. The highest incidence occurred in 1995 (110 cases/100,000 inhabitants), and the lowest occurred in 2009 (65 cases/100,000 inhabitants) (beta=-1.44; R2=0.43; p=0.0018). The highest mortality occurred in 1998 (16 deaths/100,000 inhabitants), and the lowest occurred in 2008 (5 deaths/100,000 inhabitants) (beta=-0.19; R2=0.17; p=0.07). There was a male predominance (65%), and ages ranged from 20-49 years (65%). There was a substantial increase in the number of patients that were cured after treatment (60% to 67%; p<0.001) as well as those tested for HIV (1.9% to 58.5%; p<0.001). During the first decade, clusters with p-values <0.05 included 29% of the total notified cases, and in the second decade, that percentage was 12%. CONCLUSIONS We observed a decreasing trend in incidence, which was significant, and mortality rates, which was not significant. The increased number of laboratory tests performed reflects advances in surveillance, and a reduction in the proportion of cases in primary clusters suggests, among other things, that the disease is spreading across the region. PMID- 27192592 TI - Knowledge and practices related to dengue and its vector: a community-based study from Southeast Brazil. AB - INTRODUCTION: This study investigated the knowledge of users of primary healthcare services living in Ribeirao Preto, Brazil, about dengue and its vector. METHODS: A cross-sectional survey of 605 people was conducted following a major dengue outbreak in 2013. RESULTS: Participants with higher levels of education were more likely to identify correctly the vector of the disease. CONCLUSIONS: The results emphasize the relevance of health education programs, the continuous promotion of educational campaigns in the media, the role of the television as a source of information, and the importance of motivating the population to control the vector. PMID- 27192593 TI - Spatial distribution of disseminated histoplasmosis and AIDS co-infection in an endemic area of Northeastern Brazil. AB - INTRODUCTION: The spatial distribution of disseminated histoplasmosis (DH) and acquired immunodeficiency syndrome (AIDS) co-infection in adult residents of Fortaleza, Ceara, Brazil was evaluated. METHODS: Socio-demographic data for the DH/AIDS cases were obtained from a reference hospital, and socio-environmental indicators were obtained from an official Brazilian institute. Kernel analysis and local indicators of spatial autocorrelation (LISA) cluster maps were used to estimate the case density within the city. RESULTS: DH/AIDS cases were concentrated in the Northwestern and Southwestern peripheral areas of the city, related with low human development indices, but different from AIDS cases distribution. CONCLUSION: Risk factors other than AIDS infection must affect histoplasmosis development in this area. PMID- 27192594 TI - Evaluation of human T-lymphotropic virus prevalence/co-infection rates for a four year period in a non-metropolitan blood center in Southeast Brazil. AB - INTRODUCTION: Human T-lymphotropic virus types 1/2 (HTLV-1/2) are distributed worldwide and are endemic in specific regions. METHODS: Serological evaluation of the HTLV-1/2 prevalence and co-infection rate [human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), Chagas disease, and syphilis)] for 2011-2014 was performed with volunteer blood donors from the western part of Sao Paulo State. RESULTS: Serrana and Aracatuba had higher HTLV seroprevalence rates (0.1%); while Franca, Olimpia, and Bebedouro had lower seroprevalences (0.04%). Co-infection (HBV and syphilis) was present in 12.3% of HTLV-infected blood donors. CONCLUSIONS: Our findings provide data for the prevalence of HTLV in Brazil and demonstrate the importance of regional and global hemovigilance. PMID- 27192595 TI - Prevalence and genotype distribution of human papillomavirus: implications for cancer screening and vaccination in Henan province, China. AB - INTRODUCTION: To provide information for cervical cancer screening and vaccination in Henan province, China, the distribution of human papillomavirus (HPV) was analyzed. METHODS: The HPV genotypes were detected using gene array and flow-through hybridization. RESULTS: Overall, 38.1% (1,536/4,033) of the women were human papillomavirus deoxyribonucleic acid (HPV DNA) positive. The prevalence of high-risk HPV types was 32.4%. HPV 16 was the most prevalent genotype (8.9%), followed by HPV 52 (5.8%) and HPV 58 (4.4%). CONCLUSIONS: The data support close surveillance of women for cervical cancer screening, and HPV prophylactic vaccines including HPV16, HPV 52, and HPV 58 might offer greater protection in this area. PMID- 27192596 TI - Acceptance and potential barriers to effective use of diagnostic tests for visceral leishmaniasis in an urban area in Brazil. AB - INTRODUCTION: Acceptance of the IT LEISH(r) and direct agglutination test- made in the Laboratorio de Pesquisas Clinicas (DAT-LPC) by healthcare professionals and patients suspected of visceral leishmaniasis (VL) in Ribeirao das Neves was evaluated. METHODS: Ninety-two patients and 47 professionals completed three questionnaires. RESULTS: Eighty-eight (96%) patients considered fingertip blood collection a positive test feature, and 86% (37) and 91% of professionals considered the IT LEISH(r) easy to perform and interpret, respectively. All professionals classified the DAT-LPC as simple and easy. CONCLUSIONS: Patients and healthcare professionals in Ribeirao das Neves demonstrated a high degree of acceptance of the IT LEISH(r) and DAT-LPC. PMID- 27192597 TI - New cases of Chagas disease in a rural area of Northeast Brazilian. AB - INTRODUCTION: Chagas disease is considered one of the 17 most neglected tropical diseases in the World, with the most common form of vector transmission. METHODS: This structured cross-sectional study was conducted through an epidemiological survey in the Tobias Barreto municipality of Sergipe. RESULTS: Of the 255 participants, 1 (0.4%) participant was positive for human Chagas disease. Approximately 30.2% of the participants found the triatomine bugs in their houses and outbuildings. CONCLUSIONS: The detection of a case indicated transmission, which was also evidenced by the presence of triatomines and poor housing conditions. PMID- 27192598 TI - Factors associated with non-adherence to the treatment of vivax malaria in a rural community from the Brazilian Amazon Basin. AB - INTRODUCTION We investigated the association between demographic and behavioral factors and non-adherence to antimalarial therapy. METHODS A demographic questionnaire and 5-item self-reported questionnaire regarding non-adherence were completed by 135 patients after treatment for Plasmodium vivax. RESULTS Treatment interruption, but not demographic factors, was significantly associated with non adherence to therapy. The likelihood of non-adherence was 5.16 times higher when the patients felt better than when they felt worse. The relative risk of parasitic resurgence was 3.04 times higher in non-adherent patients. CONCLUSIONS Treatment interruption is significantly associated with treatment adherence. PMID- 27192599 TI - Assessment of schistosomiasis in the semi-arid Northeast region of Brazil: the Sao Francisco River large-scale water transposition project. AB - INTRODUCTION Risk of schistosomiasis expansion to semi-arid northeastern Brazil under the influence of the Integration Project of the Sao Francisco River (IPSFR) was assessed. METHODS: Stool examinations of schoolchildren, epidemiological investigation, and survey of the local host snail Biomphalaria straminea were performed in five IPSFR municipalities. RESULTS Six of 4,770 examined schoolchildren were egg-positive for Schistosoma mansoni. Biomphalaria straminea was widespread, but not naturally infected with S. mansoni. Snails experimentally exposed to two laboratory S. mansoni strains yielded infection indices of 1-4.5%. CONCLUSIONS: There is evidence of active schistosomiasis transmission in the area; thus, intensive surveillance actions are required. PMID- 27192600 TI - Case report of vancomycin-induced pancytopenia. AB - Vancomycin is the first-line agent for the treatment of bacteremia, endocarditis, pneumonia, cellulitis, and osteomyelitis. Pancytopenia is an uncommon adverse effect of vancomycin therapy, with only a few cases of vancomycin-related neutropenia and pancytopenia described in the literature. We describe a case of a 56-year-old man who was diagnosed with chronic paraspinal abscess and started on intravenous vancomycin. He was re-admitted two weeks later with new-onset pancytopenia. Discontinuation of vancomycin resulted in improved cell counts. Physicians should monitor cell counts in patients who are on long-term intravenous vancomycin. PMID- 27192601 TI - Secondary transmission of cryptosporidiosis associated with well water consumption: two case studies. AB - Cryptosporidiosis is a very prominent disease in the field of public health, and usually causes diarrhea. We describe two immunocompetent patients who presented with chronic diarrhea that was ultimately found to be caused by continuous exposure to well water contaminated with the microbial cysts (oocysts) of the Cryptosporidium spp parasite. We describe the patients' histories and possible explanations for their prolonged symptoms. PMID- 27192602 TI - Cysticerci located in the fourth ventricle causing obstructive hydrocephalus: a radiological emergency requiring prompt diagnosis. PMID- 27192603 TI - Reply. PMID- 27192605 TI - Quantitative Identification of Biogenic Nonextractable Pesticide Residues in Soil by (14)C-Analysis. AB - Quantification of nonextractable residues (NER) of pesticides in soil is feasible by use of radioactively labeled compounds, but structural information on these long-term stabilized residues is usually lacking. Microorganisms incorporate parts of the radiolabeled ((14)C-) carbon from contaminants into microbial biomass, which after cell death enters soil organic matter, thus forming biogenic nonextractable residues (bioNER). The formation of bioNER is not yet determinable in environmental fate studies due to a lack of methodology. This paper focuses on the development of a feasible analytical method to quantify proteinaceous carbon, since proteins make up the largest mass portion of bacterial cells. The test substance (14)C-bromoxynil after 56 days forms more than 70% of NER in soil. For further characterization of NER the amino acids were extracted, purified, and separated by two-dimensional thin-layer chromatography (TLC). Visualization of the (14)C-amino acids was performed by bioimaging, unambiguous identification by GC-MS and LC-MS/MS. Our analysis revealed that after 56 days of incubation about 14.5% of the (14)C-label of bromoxynil was incorporated in amino acids. Extrapolating this content based on the amount of proteins in the biomass (55%), in total about 26% of the NER is accounted for by bioNER and thus is not environmentally relevant. PMID- 27192604 TI - Shift of the Muscular Inhibition Latency during On-Line Acquisition of Anticipatory Postural Adjustments. AB - During action, Anticipatory Postural Adjustments (APAs) cancel the consequences of a movement on postural stabilization. Their muscular expression is characterized by early changes in the activity of the postural muscles, before the movement begins. To explore the mechanisms enabling the acquisition of APAs, a learning paradigm was designed in which the voluntary lifting of a load with one hand triggered the unloading of another load suspended below the contralateral forearm. The aim of this study was to investigate changes in the muscular expression that uncovers the progressive learning of new APAs. A trial by-trial analysis of kinematic and electromyographic signals recorded on the right arm was conducted in twelve adults through six sessions of learning. Kinematic results reported an enhancement of the postural stabilization across learning. The main EMG pattern found during learning consisted of a flexor inhibition, where latency was shifted towards an earlier occurrence in parallel with the improvement of the postural performance. A linear regression analysis conducted between the inhibition latency and the maximal amplitude of elbow rotation showed that the earlier the inhibition onset, the better the postural stabilization. This study revealed that the progressive shift of the postural flexor inhibition latency could be considered as a reliable neurophysiological marker of the progressive learning of new APAs. Importantly, this marker could be used to track motor learning abnormalities in pathology. We relate our findings to the update of a forward predictive model of action, defined as a system that predicts beforehand the consequences of the action on posture. PMID- 27192607 TI - Odor composition analysis and odor indicator selection during sewage sludge composting. AB - On the basis of total temperature increase, normal dehydration, and maturity, the odor compositions of surface and internal piles in a well-run sewage sludge compost plant were analyzed using gas chromatography-mass spectrometry with a liquid nitrogen cooling system and a portable odor detector. Approximately 80 types of substances were detected, including 2 volatile inorganic compounds, 4 sulfur organic compounds, 16 benzenes, 27 alkanes, 15 alkenes, and 19 halogenated compounds. Most pollutants were mainly produced in the mesophilic and pre thermophilic periods. The sulfur volatile organic compounds contributed significantly to odor and should be controlled primarily. Treatment strategies should be based on the properties of sulfur organic compounds. Hydrogen sulfide, methyl mercaptan, dimethyl disulfide, dimethyl sulfide, ammonia, and carbon disulfide were selected as core indicators. Ammonia, hydrogen sulfide, carbon disulfide, dimethyl disulfide, methyl mercaptan, dimethylbenzene, phenylpropane, and isopentane were designated as concentration indicators. Benzene, m-xylene, p xylene, dimethylbenzene, dichloromethane, toluene, chlorobenzene, trichloromethane, carbon tetrachloride, and ethylbenzene were selected as health indicators. According to the principle of odor pollution indicator selection, dimethyl disulfide was selected as an odor pollution indicator of sewage sludge composting. Monitoring dimethyl disulfide provides a highly scientific method for modeling and evaluating odor pollution from sewage sludge composting facilities. IMPLICATIONS: Composting is one of the most important methods for sewage sludge treatment and improving the low organic matter content of many agricultural soils. However, odors are inevitably produced during the composting process. Understanding the production and emission patterns of odors is important for odor control and treatment. Core indicators, concentration indicators, and health indicators provide an index system to odor evaluation. An odor pollution indicator provides theoretical support for further modelling and evaluating odor pollution from sewage sludge composting facilities. PMID- 27192606 TI - Diversity of fungi from the mound nests of Formica ulkei and adjacent non-nest soils. AB - Culture-based methods were employed to recover 3929 isolates of fungi from soils collected in May and July 2014 from mound nests of Formica ulkei and adjacent non nest sites. The abundance, diversity, and richness of species from nest mounds exceeded those of non-mound soils, particularly in July. Communities of fungi from mounds were more similar to those from mounds than non-mounds; this was also the case for non-mound soils with the exception of one non-mound site in July. Species of Aspergillus, Paecilomyces, and Penicillium were dominant in nest soils and represented up to 81.8% of the taxa recovered. Members of the genus Aspergillus accounted for the majority of Trichocomaceae from nests and were represented almost exclusively by Aspergillus navahoensis and Aspergillus pseudodeflectus. Dominant fungi from non-mound sites included Cladosporium cladosporioides, Geomyces pannorum, and species of Acremonium, Fusarium, Penicillium, and Phoma. Although mound nests were warmer than adjacent soils, the dominance of xerotolerant Aspergillus in soils from mounds and the isolation of the majority of Trichocomaceae at 25 and 35 degrees C suggests that both temperature and water availability may be determinants of fungal community structure in nests of F. ulkei. PMID- 27192608 TI - Direct Mapping of Charge Distribution during Lithiation of Ge Nanowires Using Off Axis Electron Holography. AB - The successful operation of rechargeable batteries relies on reliable insertion/extraction of ions into/from the electrodes. The battery performance and the response of the electrodes to such ion insertion and extraction are directly related to the spatial distribution of the charge and its dynamic evolution. However, it remains unclear how charge is distributed in the electrodes during normal battery operation. In this work, we have used off-axis electron holography to measure charge distribution during lithium ion insertion into a Ge nanowire (NW) under dynamic operating conditions. We discovered that the surface region of the Ge core is negatively charged during the core-shell lithiation of the Ge NW, which is counterbalanced by positive charge on the inner surface of the lithiated LixGe shell. The remainder of the lithiated LixGe shell is free from net charge, consistent with its metallic characteristics. The present work provides a vivid picture of charge distribution and dynamic evolution during Ge NW lithiation and should form the basis for tackling the response of these and related materials under real electrochemical conditions. PMID- 27192609 TI - Older Single Gay Men's Body Talk: Resisting and Rigidifying the Aging Discourse in the Gay Community. AB - Previous research saw older gay men as subject to structural marginalization of ageism but yet possessing agency to interpret aging in diverse ways. I move beyond this duality, drawing on the theory of defensive othering to understand how older gay men live with the aging discourse in the gay community. Informed by grounded theory, I analyzed interviews with 25 self-identified single gay men aged 50 or above in England inductively. It emerged that many older gay men found it difficult to escape the discourse that marginalizes the aging body. Even when they argued they were the exception and "looked good," they were discursively producing a two-tier system: they themselves as the "good older gay men," as opposed to the other "bad older gay men," who "had given up." Such a defensive othering tactic seemingly allowed them to resist age norms from applying to them personally, but unintentionally reinforced an ageist discourse. PMID- 27192610 TI - Stent implantation to relieve native obstructed left partial anomalous pulmonary venous connections. AB - Obstructed partial anomalous pulmonary venous connections (APVC) are rare but may be associated with severe pulmonary hypertension (PHTN) and warrant urgent relief. There are a number of case reports of successful catheter intervention for obstructed total APVC. We present the first reported case of catheter intervention to relieve obstructed, left sided PAPVC in a neonate with Turner syndrome. (c) 2016 Wiley Periodicals, Inc. PMID- 27192611 TI - Microfluidic Fabrication of Pluronic Vesicles with Controlled Permeability. AB - Block copolymers with a low hydrophilic-to-lipophilic balance form membranes that are highly permeable to hydrophilic molecules. Polymersomes with this type of membrane enable the controllable release of molecules without membrane rupture. However, these polymersomes are difficult to assemble because of their low hydrophobicity. Here, we report a microfluidic approach to the production of these polymersomes using double-emulsion drops with ultrathin shells as templates. The small thickness of the middle oil phase enables the attraction of the hydrophobic blocks of the polymers adsorbed at each of the oil/water interfaces of the double emulsions; this results in the dewetting of the oil from the surface of the innermost water drops of the double emulsions and the ultimate formation of the polymersome. This approach to polymersome fabrication enables control of the vesicle size and results in the efficient encapsulation of hydrophilic ingredients that can be released through the polymer membrane without membrane rupture. We apply our approach to the fabrication of Pluronic L121 vesicles and characterize the permeability of their membranes. Furthermore, we show that membrane permeability can be tuned by blending different Pluronic polymers. Our work thus describes a route to producing Pluronic vesicles that are useful for the controlled release of hydrophilic ingredients. PMID- 27192612 TI - Enhanced gas sorption and breathing properties of the new sulfone functionalized COMOC-2 metal organic framework. AB - A new sulfone functionalized vanadium metal-organic framework (MOF), denoted as SO2-COMOC-2, has been synthesized solvothermally. Its structural and gas sorption properties towards CO2 and CH4 have been evaluated and compared to those of the pristine COMOC-2 material. The SO2-COMOC-2 shows a remarkable increase in CO2 capacity at ambient pressure (2.13 mmol g(-1) at 273 K vs. 1.23 mmol g(-1) for the pristine COMOC-2). Additionally, the high pressure CO2 sorption isotherm shows a distinctive two-step sorption behavior with a final capacity of 12.45 mmol g(-1) for SO2-COMOC-2 at 303 K, while for CH4 a typical Type I isotherm was obtained with a capacity of 4.13 mmol g(-1). In situ synchrotron X-ray powder diffraction measurements have been carried out to characterize the structural flexibility of the materials, showing both the presence of large pore and narrow pore form. Furthermore, synchrotron XANES and a variety of spectroscopic techniques have been utilized to verify the presence of hydroxyl groups and the existence of the mixed vanadium oxidation states in the titled MOF structure. PMID- 27192613 TI - Power morcellation inside a secure endobag: a pilot study. AB - INTRODUCTION: Unprotected power morcellation can lead to a spread of previously undiagnosed malignancy. We present a new containment bag with two closable trocar insertion sites to reduce this risk. This pilot study was designed to assess the feasibility of this device under everyday conditions. MATERIAL AND METHODS: The containment bag was used in ten laparoscopic supracervical hysterectomies. We evaluated time requirement for bag insertion into the abdominal cavity and in-bag morcellation. A 2000 ml polyurethane morcellation bag was used for all interventions. All surgeries were carried out in a three-trocar setting. RESULTS: We carried out ten supracervical hysterectomies. No intraoperative complications and no bag ruptures occurred. The meantime requirement to insert the bag and prepare the specimen for morcellation was 10.5 min (range, 7-19 min). The mean specimen weight was 191.9 g (range, 32-710 g). Mean morcellation time was 10.5 min (range, 3-28 min), mean weight of remaining tissue and fluid in the bag after morcellation was 12.1 g (range, 7-19 g). CONCLUSIONS: The presented data demonstrate that the endobag can be successfully applied in the clinical routine. Further studies are required to evaluate additional characteristics, such as individual learning curve and time requirements. PMID- 27192615 TI - Synthesis of [60]Fullerene-Fused Spiroindanes by Palladium-Catalyzed Oxidative Annulation of [60]Fullerene with 2-Aryl Cyclic 1,3-Dicarbonyl Compounds. AB - A convenient and facile palladium-catalyzed reaction of [60]fullerene (C60) with 2-aryl cyclic 1,3-dicarbonyl compounds via the enolate-directed sp(2) C-H activation and sp(3) C-H functionalization has been exploited to synthesize the novel and rare C60-fused spiroindanes for the first time. This reaction is easy to perform with broad substrate scope and provides diversified products in 20-50% yields. A plausible reaction mechanism involving the palladium-catalyzed enolate directed C-H activation and subsequent cyclization has been proposed, and the electrochemistry of the C60-fused spiroindanes has also been investigated. PMID- 27192614 TI - Bayesian Top-Down Protein Sequence Alignment with Inferred Position-Specific Gap Penalties. AB - We describe a Bayesian Markov chain Monte Carlo (MCMC) sampler for protein multiple sequence alignment (MSA) that, as implemented in the program GISMO and applied to large numbers of diverse sequences, is more accurate than the popular MSA programs MUSCLE, MAFFT, Clustal-Omega and Kalign. Features of GISMO central to its performance are: (i) It employs a "top-down" strategy with a favorable asymptotic time complexity that first identifies regions generally shared by all the input sequences, and then realigns closely related subgroups in tandem. (ii) It infers position-specific gap penalties that favor insertions or deletions (indels) within each sequence at alignment positions in which indels are invoked in other sequences. This favors the placement of insertions between conserved blocks, which can be understood as making up the proteins' structural core. (iii) It uses a Bayesian statistical measure of alignment quality based on the minimum description length principle and on Dirichlet mixture priors. Consequently, GISMO aligns sequence regions only when statistically justified. This is unlike methods based on the ad hoc, but widely used, sum-of-the-pairs scoring system, which will align random sequences. (iv) It defines a system for exploring alignment space that provides natural avenues for further experimentation through the development of new sampling strategies for more efficiently escaping from suboptimal traps. GISMO's superior performance is illustrated using 408 protein sets containing, on average, 235 sequences. These sets correspond to NCBI Conserved Domain Database alignments, which have been manually curated in the light of available crystal structures, and thus provide a means to assess alignment accuracy. GISMO fills a different niche than other MSA programs, namely identifying and aligning a conserved domain present within a large, diverse set of full length sequences. The GISMO program is available at http://gismo.igs.umaryland.edu/. PMID- 27192618 TI - Antimicrobial prophylaxis for surgery. PMID- 27192616 TI - Synthetic and Receptor Signaling Explorations of the Mitragyna Alkaloids: Mitragynine as an Atypical Molecular Framework for Opioid Receptor Modulators. AB - Mu-opioid receptor agonists represent mainstays of pain management. However, the therapeutic use of these agents is associated with serious side effects, including potentially lethal respiratory depression. Accordingly, there is a longstanding interest in the development of new opioid analgesics with improved therapeutic profiles. The alkaloids of the Southeast Asian plant Mitragyna speciosa, represented by the prototypical member mitragynine, are an unusual class of opioid receptor modulators with distinct pharmacological properties. Here we describe the first receptor-level functional characterization of mitragynine and related natural alkaloids at the human mu-, kappa-, and delta opioid receptors. These results show that mitragynine and the oxidized analogue 7 hydroxymitragynine, are partial agonists of the human mu-opioid receptor and competitive antagonists at the kappa- and delta-opioid receptors. We also show that mitragynine and 7-hydroxymitragynine are G-protein-biased agonists of the mu opioid receptor, which do not recruit beta-arrestin following receptor activation. Therefore, the Mitragyna alkaloid scaffold represents a novel framework for the development of functionally biased opioid modulators, which may exhibit improved therapeutic profiles. Also presented is an enantioselective total synthesis of both (-)-mitragynine and its unnatural enantiomer, (+) mitragynine, employing a proline-catalyzed Mannich-Michael reaction sequence as the key transformation. Pharmacological evaluation of (+)-mitragynine revealed its much weaker opioid activity. Likewise, the intermediates and chemical transformations developed in the total synthesis allowed the elucidation of previously unexplored structure-activity relationships (SAR) within the Mitragyna scaffold. Molecular docking studies, in combination with the observed chemical SAR, suggest that Mitragyna alkaloids adopt a binding pose at the mu-opioid receptor that is distinct from that of classical opioids. PMID- 27192619 TI - QuilliChew ER--extended-release chewable methylphenidate tablets. PMID- 27192620 TI - Ciprofloxacin (Otiprio) for tympanostomy tube insertion. PMID- 27192621 TI - Three new drugs for multiple myeloma. PMID- 27192622 TI - Subaerial biofilms on granitic historic buildings: microbial diversity and development of phototrophic multi-species cultures. AB - Microbial communities of natural subaerial biofilms developed on granitic historic buildings of a World Heritage Site (Santiago de Compostela, NW Spain) were characterized and cultured in liquid BG11 medium. Environmental barcoding through next-generation sequencing (Pacific Biosciences) revealed that the biofilms were mainly composed of species of Chlorophyta (green algae) and Ascomycota (fungi) commonly associated with rock substrata. Richness and diversity were higher for the fungal than for the algal assemblages and fungi showed higher heterogeneity among samples. Cultures derived from natural biofilms showed the establishment of stable microbial communities mainly composed of Chlorophyta and Cyanobacteria. Although most taxa found in these cultures were not common in the original biofilms, they are likely common pioneer colonizers of building stone surfaces, including granite. Stable phototrophic multi-species cultures of known microbial diversity were thus obtained and their reliability to emulate natural colonization on granite should be confirmed in further experiments. PMID- 27192623 TI - Flexor Digitorum Superficialis Tear in a Wakeboarder: An Unusual Clinical Case. AB - Tears in the flexor digitorum superficialis muscle belly are rare injuries with one single case reported in the literature. In this article, we describe the first case of muscle tear of the flexor digitorum superficialis resulting from a wakeboarding trauma. The wakeboarder presented with pain localized in the anterior forearm, and early symptoms of carpal tunnel syndrome. Ultrasonography demonstrated an intramuscular hematoma of the flexor digitorum superficialis myotendinous junction, which compressed the median nerve. After conservative treatment, the patient was asymptomatic and returned to his usual daily activities and sports within 5 weeks of the injury. In patients with a wakeboard trauma and similar presentations, a tear in the flexor digitorum superficialis muscle belly should be suspected. PMID- 27192627 TI - Toxicity assessment of boron (B) by Lemna minor L. and Lemna gibba L. and their possible use as model plants for ecological risk assessment of aquatic ecosystems with boron pollution. AB - As many of the metalloid-based pollutants, the boron (B) toxicity issues have aroused more and more global attentions, especially concerning drinking water sources which flow through boron-rich areas. Therefore, feasible and innovative approaches are required in order to assess B toxicity in aquatic ecosystems. In this study, the toxic effects of B on Lemna minor L. and Lemna gibba L. were investigated using various endpoints including number of fronds, growth rates, dry biomass and antioxidants enzymatic activities. Lemna species were exposed to B concentrations of 2 (control), 4, 8, 16, 32, 64 and 128 mg L(-1) for a test period of 7 days. The results demonstrated that plant growth was significantly reduced when the B concentration reached 16 mg L(-1). Furthermore, our results also concluded that among the antioxidative enzymes, SOD, APX and GPX can serve as important biomarkers for B-rich environment. The present results suggested that L. minor and L. gibba are very useful model plants for phytoremediation of low-B contaminated wastewater and they are also suitable options for B biomonitoring due to high phototoxic sensitivity against B. In this respect, the scientific insight of the present study is to fill the gaps in the research about the use of L. minor and L. gibba in ecotoxicological research associated with B toxicity. PMID- 27192628 TI - MicroRNA-590-5p Stabilizes Runx2 by Targeting Smad7 During Osteoblast Differentiation. AB - Mesenchymal stem cells (MSCs) are multipotent cells and their differentiation into the osteoblastic lineage is strictly controlled by several regulators, including microRNAs (miRNAs). Runx2 is a bone transcription factor required for osteoblast differentiation. Here, we used in silico analysis to identify a number of miRNAs that putatively target Runx2 and its co-factors to mediate both positive and negative regulation of osteoblast differentiation. Among these miRNAs, miR-590-5p was selected and its expression was found to be increased during osteoblast differentiation. When mouse MSCs (mMSCs) were transiently transfected with a miR-590-5p mimic, we detected an increase in both calcium deposition and the mRNA expression of osteoblast differentiation marker genes such as alkaline phosphatase (ALP) and type I collagen genes. Smad7 was found to be among the putative target genes of miR-590-5p and its mRNA and protein expression decreased after miR-590-5p mimic transfection in human osteoblast-like cells (MG63). Our analysis indicated that Runx2 was not a putative target of miR 590-5p. However, Runx2 protein, but not mRNA expression, increased after miR-590 5p mimic transfection in MG63 cells. Runx2 protein expression was increased with knockdown of Smad7 expression by Smad7 siRNA in these cells. We further identified that the 3'-untranslated region of Smad7 was directly targeted by miR 590-5p; this was done using the luciferase reporter gene system. It is known that Smad7 inhibits osteoblast differentiation via Smurf2-mediated Runx2 degradation. Hence, based on our results, we suggest that miR-590-5p promotes osteoblast differentiation by indirectly protecting and stabilizing the Runx2 protein by targeting Smad7 gene expression. J. Cell. Physiol. 232: 371-380, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27192629 TI - Manipulation of Rumen Microbial Fermentation by Polyphenol Rich Solvent Fractions from Papaya Leaf to Reduce Green-House Gas Methane and Biohydrogenation of C18 PUFA. AB - Different solvents (hexane, chloroform, ethyl acetate, butanol, and water) were used to identify the effect of papaya leaf (PL) fractions (PLFs) on ruminal biohydrogenation (BH) and ruminal methanogenesis in an in vitro study. PLFs at a concentration of 0 (control, CON) and 15 mg/250 mg dry matter (DM) were mixed with 30 mL of buffered rumen fluid and were incubated for 24 h. Methane (CH4) production (mL/250 mg DM) was the highest (P < 0.05) for CON (7.65) and lowest for the chloroform fraction (5.41) compared to those of other PLFs at 24 h of incubation. Acetate to propionate ratio was the lowest for PLFs compared to that of CON. Supplementation of the diet with PLFs significantly (P < 0.05) decreased the rate of BH of C18:1n-9 (oleic acid; OA), C18:2n-6 (linoleic acid; LA), and C18:3n-3 (alpha-linolenic acid; LNA) compared to that of CON after 24 h of incubation. Real time PCR indicated that total protozoa and total methanogen population in PLFs decreased (P < 0.05) compared to those of CON. PMID- 27192630 TI - Cycloheximide Inhibits Actin Cytoskeletal Dynamics by Suppressing Signaling via RhoA. AB - Genome-wide screening of the yeast Saccharomyces cerevisiae knockout collection was used to characterize chemical-genetic interactions of cycloheximide (CHX). The results showed that while the act1Delta mutant was the only deletion mutant in the heterozygous essential gene deletion collection that showed hypersensitivity to sub-inhibitory concentrations of CHX, deletion of nonessential genes that work in concert with either cytoplasmic or nuclear actin in the homozygous deletion collection also highly sensitized yeast to CHX. Fluorescence microscopy analysis revealed that CHX disrupts filamentous actin structures and fluid phase endocytosis in the yeast cell. It also showed that CHX disrupts transforming growth factor-beta1 (TGF-beta1)-induced actin reorganization and polygonal architecture of microfilaments in mammalian cells. This inhibitory effect is mediated, at least in part, through the actin dynamics signaling pathway via suppression of activation of the small GTPase RhoA. J. Cell. Biochem. 117: 2886-2898, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27192631 TI - Echocardiographic measures of atrial function may predict atrial fibrillation in stroke patients. AB - OBJECTIVE: In patients with a prior stroke or transient ischemic attack (TIA) and atrial fibrillation anticoagulant treatment is indicated. This study's purpose was to investigate if echocardiography can predict unknown AF in patients after stroke. DESIGN: Prospectively, 174 stroke/TIA patients without diagnosed AF underwent echocardiographic evaluation including tissue Doppler imaging (TDI) focusing on functional parameters of the left atrium and left ventricular diastolic function. AF screening was performed during 30 d. RESULTS: Fifteen patients (8.6%) were diagnosed with AF. Echocardiography in the AF group compared to those without AF, showed larger left atrial volume index (LAVI), (37.2 +/- 6.7 vs. 31.6 +/- 8.6 ml/m(2), p = 0.018), lower A' velocities in ventricular (5.9 +/- 2.2 vs. 7.2 +/- 1.6, p = 0.010) and atrial (4.8 +/- 1.4 vs. 5.9 +/- 1.4, p = 0.013) septa, higher LAVI/A' in ventricular septum (6.7 (5.0-8.7) vs. 4.2 (3.2 5.5), p = 0.001) and atrial septum (8.5 (5.9-11.0) vs. 5.1 (4.1-6.8), p = 0.003). Receiver operating characteristic analyses to detect AF was performed, area under the curve for LAVI was 0.71 (0.61-0.83), p = 0.008, and for LAVI/A' in ventricular septum 0.76 (0.59-0.93), p = 0.006 and atrial septum 0.78 (0.63 0.93), p = 0.002, respectively. CONCLUSIONS: LAVI and measures of atrial contraction as measured by TDI predict unknown AF in patients after an stroke/TIA and may be used to detect silent AF. PMID- 27192632 TI - Isolation and identification of biocontrol agent Streptomyces rimosus M527 against Fusarium oxysporum f. sp. cucumerinum. AB - Actinomycetes have received considerable attention as biocontrol agents against fungal plant pathogens and as plant growth promoters. In this study, a total of 320 actinomycetes were isolated from various habitats in China. Among which, 77 strains have been identified as antagonistic activities against Fusarium oxysporum f. sp. cucumerinum which usually caused fusarium wilt of cucumber. Of these, isolate actinomycete M527 not only displayed broad-spectrum antifungal activity but also showed the strongest antagonistic activity against the spore germination of F. oxysporum f. sp. cucumerinum. In pot experiments, the results indicated that isolate M527 could promote the shoot growth and prevent the development of the disease on cucumber caused by F. oxysporum f. sp. cucumerinum. The control efficacy against seedling fusarium wilt of cucumber after M527 fermentation broth root-irrigation was up to 72.1% as compared to control. Based on 16S rDNA sequence analysis, the isolate M527 was identified as Streptomyces rimosus. PMID- 27192634 TI - Historical Vignettes of Epicanthoplasty. AB - The aim of this study is to summarize historical vignettes in regards to epicanthoplasty, systematically.In a PubMed search and a Scopus search, the search terms (epicanthal) AND (fold)and (epicanthoplasty) were used, which resulted in 389 titles found. Among the 480 titles, 74 titles, which were duplicated between PubMed and Scopus were excluded. Excluding 352 titles from the remaining 406 titles, 54 abstracts discussing at least 1 surgical method correcting epicanthal folds were reviewed. By excluding further 6 abstracts, 48 full articles, were reviewed. Finally, 6 mined articles were added, in which 4 studies were excluded resulting in 46 articles being analyzed.Forty-three articles studied eliminating epicanthal folds (93.5%) and 3 discussed reconstructing removed epicanthal folds (6.5%). The methods were categorized into Z-plasty, advancement, skin redraping, excision, and others. Among the 48 methods analyzed, the Z-plasty (21, 43.8%) was written most frequently followed by advancement (14, 29.2%), and excision (7, 14.6%). Redraping was relatively rare (4, 8.3%). The Z-plasty is employed frequently and is increasingly used. Excision has decreased in use and no more articles have been written recently. Advancement has continuously increased but has stabilized from 2010. Redraping has increased recently apparently after Oh's 2007 article was published.Excessive performance of epicanthoplasty causes unwanted results, including overcorrection. Subsequently, reconstruction of the over-corrected cases was needed and restoration methods are now being published. It is expected that new modifications of Z-epicanthoplasty or skin redraping technique will appear. Reconstruction methods will also be developed. PMID- 27192635 TI - Analysis of Rib Cartilages Anomalies in Patients With Microtia. AB - OBJECTIVE: The objective of this study was to identify the characteristics and incidence of rib cartilages anomalies in patients with microtia and to investigate the interaction between microtia and rib cartilages anomalies. METHODS: A total of 214 consecutive patients received a preoperative 3 dimensional chest computed tomography. A retrospective study was performed with the clinical and imaging data from November 2014 to July 2015. Pearson X2 test and Spearman analysis were used to analyze the interaction between microtia and rib cartilages anomalies. RESULTS: With the 3-dimensional chest computed tomography images, a total of 62 patients (29.0%) were documented with rib cartilages anomalies including 4 patients (1.9%) with numerical variations, 13 patients (6.1%) with structural changes, and 51 patients (23.8%) with abnormal articulations. The incidence of rib anomalies (P = 0.035) varied with grades of microtia. CONCLUSIONS: The incidence of rib cartilages anomalies was high in patients with microtia. The authors observed a higher incidence of costal cartilages anomalies in patients with a more serious grade of microtia. Microtia with rib cartilages anomalies may involve a new syndrome previously undiscovered or just another extension with the very wide spectrum of microtia. PMID- 27192636 TI - Empowerment of Parents of Children With Craniosynostosis by Objective Scoring of Patient Information Websites. AB - INTRODUCTION: Parental anxiety may be caused by inappropriate information on the world wide web regarding craniosynostosis. The aim of this study was to study the correlation between the first 100 websites ranked on the Google search engine and those ranked based on objective scoring with patient information scoring tool. The results of these findings can then be used to recommend websites based on the quality of information that may not initially appear first on a search engine. METHODS: The DISCERN patient information scoring tool was chosen as a scientific way of measuring the quality of patient information based on previous research by the Picker Institute in Oxford. The word "craniosynostosis" was entered into the Google internet search engine. Patient information provided by the first 100 websites was studied and scored using the DISCERN scoring tool. From this score, each website was ranked with the highest scoring website at the top and worse scoring website at the bottom. This ranking based on the DISCERN tool score was correlated against the ranking of the website by Google. Positive correlation between DISCERN and Google ranking would be demonstrated if a website high in the ranking using DISCERN was also at the top of the first 100 websites on Google. RESULTS: No correlation could be found between those websites ranked highly for patient information on craniosynostosis using the DISCERN tool to the ranking provided by Google. DISCERN scores ranged from 17 to 72 (the lowest possible DISCERN tool score being 15 and the highest 85). The website ranking highest in terms of quality appeared only 50th in the Google rank. CONCLUSION: High-quality patient information on craniosynostosis does exist on the world wide web but may be difficult to find due to the complexity of factors used to rank websites on internet search engines. This results in some high-quality websites not appearing at the top of an internet search. Therefore, parents risk missing useful information relevant to their child's diagnosis. Healthcare professionals can use objective scoring of patient information websites to empower their patients to seek higher quality information. PMID- 27192637 TI - A Novel Local Autologous Bone Graft Donor Site After Scalp Tissue Expansion in Aplasia Cutis Congenita. AB - Aplasia cutis congenita (ACC) is a rare condition often presenting as an absent area of cutaneous scalp. The calvarium and dura may also be affected. Scalp reconstruction with tissue expansion is often needed for large defects. Patients involving deficient calvarial bone present a dilemma for the reconstructive surgeon, because bone graft donor sites are limited in young children.A thick, bony rim has been noted to form around the periphery of scalp tissue expanders. The authors present a series of 3 patients with ACC for whom this bony hyperostosis was used as donor particulate bone graft at the time of scalp tissue expansion. There was 85 to 100% graft ossification on postoperative computed tomography scan. There were no bone graft-related complications.In conclusion, the hyperostotic rim that forms after scalp tissue expansion can be successfully used as particulate bone graft, decreasing the number of procedures needed for patient with ACC and obviating the need for other donor sites. PMID- 27192633 TI - Great expectations: racial differences in outcome expectations for a weight lifting intervention among black and white breast cancer survivors with or without lymphedema. AB - BACKGROUND: Black breast cancer survivors are less likely to engage in physical activity than are White survivors. This is unfortunate because physical activity may be especially beneficial given Black breast cancer survivors' higher rates of obesity and adverse treatment effects related to obesity, such as breast cancer related lymphedema (BCRL). The analysis explored outcome expectations for a weight lifting intervention by sedentary Black or White female breast cancer survivors and assessed the role of BCRL on outcome expectations for exercise. METHODS: Chi-squared tests compared mean outcome expectation values for Black and White breast cancer survivors who completed baseline surveys for the Physical Activity and Lymphedema trial (n = 281). With race as the independent variable, multivariable analysis compared results for women without BCRL with those with BCRL, separately. RESULTS: Across the entire sample, Black survivors (n = 90) had significantly higher (p < 0.05) outcome expectations than White survivors (n = 191) for improvements in sleep, appearance, mental health, affect, energy, and eating habits, with small to moderate effect sizes. When stratified by BCRL status, differences by race were robust only among those with BCRL. CONCLUSIONS: Black cancer survivors had greater expectations than White cancer survivors for how a weight lifting intervention would improve their physical and mental states; these differences were most apparent among women with BCRL. Improving outcomes in Black breast cancer survivors rests on the development of interventions that are appropriately tailored to address the expectations of this population and account for differences in persistent adverse effects of cancer such as BCRL. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27192638 TI - Applying Craniofacial Principles to Neurosurgical Exposures in Cerebrovascular Aneurysm Repair. AB - The subspecialty of craniofacial surgery emphasizes skeletal exposure, preservation of critical structures, and provision of a superior cosmetic result. In recent decades, an emphasis on minimally invasive neurosurgical exposure has paved the way for increased collaboration between neurosurgeons and craniofacial surgeons.The 1990s saw the growing popularity of an eyebrow incision for orbital roof craniotomies in neurosurgery to address lesions in the anterior skull base. Disadvantages of this approach included conspicuous scarring above the brow skin, risk of injury to the frontal branch of the facial nerve, and numbness from supraorbital or supratrochlear nerve transection.A transpalpebral approach was first described in 2008 in the neurosurgical literature. An approach familiar to the craniofacial surgeon, transpalpebral exposure is used for zygomaticomaxillary complex fractures as well as aesthetic brow and periorbital surgery.In conjunction with neurosurgery, the authors have applied craniofacial principles to address the major pitfalls of the transpalpebral craniotomy. The authors present their patient series experience. Hopefully, in the future, other institutions will have increased collaboration between craniofacial surgeons and neurosurgeons. PMID- 27192639 TI - Does Simultaneous Third Molar Extraction Increase Intraoperative and Perioperative Complications in Orthognathic Surgery? AB - BACKGROUND: Prior to orthognathic surgery, most surgeons recommend third molar extraction. Espoused reasons include potential risk for infection, untoward osteotomies, and worsened postoperative discomfort. However, in addition to being another procedure for the patient, this may necessitate a longer preorthognathic surgery phase. The purpose of this study is to compare the outcomes of orthognathic surgery with staged versus simultaneous third molar extractions. METHODS: This was a retrospective analysis of patients who underwent orthognathic surgery from 2013 to 2014, with at least a 1-year follow-up period. Patients were stratified into 2 groups: Extraction of third molars at the time of surgery and prior extraction of third molars. Primary outcomes included the occurrence of unfavorable splits, infection, bleeding, malocclusion, and hardware failure. Secondary outcomes were procedure time, postoperative pain, and length of stay. Pearson chi tests and 2-tailed unpaired t tests were performed to determine if there was an association between the simultaneous removal of third molars and the primary and secondary outcome measures, respectively. RESULTS: One hundred patients were included in the study. Forty-nine patients had third molars extracted at the time of surgery and fifty-one did not. Complications included unfavorable split, postoperative infection, mild postoperative bleeding, postoperative malocclusion, and hardware failure. There was no significant difference in the incidence of complications in both groups. Procedure time was not considerably increased with extractions. There was no significant difference in postoperative pain or length of stay between both groups. CONCLUSIONS: Removing third molars concurrently with orthognathic surgery does not increase the risk of adverse outcomes, nor does it significantly influence hospital course. PMID- 27192641 TI - Surgeon-Friendly Anatomy. PMID- 27192640 TI - Combined External-Endoscopic Endonasal Assisted Removal of a Nail Gun. AB - Management of penetrating trauma to the paranasal sinuses with retained foreign bodies represents a challenge due to the proximity to vital neurovascular structures. The authors report the successful treatment of a patient with a work related nail gun injury, carried out by means of a combined endoscopic endonasal external assisted procedure.A transnasal endoscopic approach was planned to minimize inadvertent movements of the nail during surgery and in case necessary to repair the orbit or skull base. No major bleeding or neurovascular complication was observed after surgery and a computed tomography scan was performed after surgery confirming the complete removal of the nail and with no damage of the orbit nor the skull base. PMID- 27192642 TI - Reconstruction of Congenital Isolated Alar Defect Using Mutaf Triangular Closure Technique in Pediatric Patients. AB - Congenital isolated alar defects are extremely rare, occurring in approximately 1 in 20,000 to 40,000 live births. The patients are presented here of 2 pediatric patients operated on for congenital isolated alar defect. The reconstruction of congenital isolated alar defects was made in a 3-layered fashion. The skin defects were covered using the Mutaf triangular closure technique in which 2 cutaneous local flaps are designed in an unequal Z-plasty manner. Conchal cartilage graft was used between the skin and mucosal closure to replace the missing part of the lower lateral cartilage in these patients. The early results were promising in Patient 1, but sufficient improvement was detected in the alar cartilage postoperative follow-up period in Patient 2. Hence, this patient required revision 1 to 2 years postoperatively. This technique provides excellent aesthetic and functional results, except for this problem in Tessier 2 cleft patients. The use of the Stair step flap technique with Mutaf triangle closure technique achieved cosmetically and functionally excellent results in the reconstruction and repair of a large, irregular, narrow cleft, in the inadequate rotation of the lateral part of the lower lateral cartilage. However, because of this problem, evaluation of the long-term follow-up of patients is necessary. PMID- 27192643 TI - Cranioplasty Enhanced by Three-Dimensional Printing: Custom-Made Three Dimensional-Printed Titanium Implants for Skull Defects. AB - The authors studied to demonstrate the efficacy of custom-made three-dimensional (3D)-printed titanium implants for reconstructing skull defects. From 2013 to 2015, 21 patients (8-62 years old, mean = 28.6-year old; 11 females and 10 males) with skull defects were treated. Total disease duration ranged from 6 to 168 months (mean = 33.6 months). The size of skull defects ranged from 84 * 104 to 154 * 193 mm. Custom-made implants were manufactured by Medyssey Co, Ltd (Jecheon, South Korea) using 3D computed tomography data, Mimics software, and an electron beam melting machine. The team reviewed several different designs and simulated surgery using a 3D skull model. During the operation, the implant was fit to the defect without dead space. Operation times ranged from 85 to 180 minutes (mean = 115.7 minutes). Operative sites healed without any complications except for 1 patient who had red swelling with exudation at the skin defect, which was a skin infection and defect at the center of the scalp flap reoccurring since the initial head injury. This patient underwent reoperation for skin defect revision and replacement of the implant. Twenty-one patients were followed for 6 to 24 months (mean = 14.1 months). The patients were satisfied and had no recurrent wound problems. Head computed tomography after operation showed good fixation of titanium implants and satisfactory skull-shape symmetry. For the reconstruction of skull defects, the use of autologous bone grafts has been the treatment of choice. However, bone use depends on availability, defect size, and donor morbidity. As 3D printing techniques are further advanced, it is becoming possible to manufacture custom-made 3D titanium implants for skull reconstruction. PMID- 27192644 TI - Utility of Cartilage Grafts Wrapped With Amniotic Membrane in Dorsal Nasal Augmentation. AB - OBJECTIVES: The success of rhinoplasty may be compromised with postoperative problems like rough and rigid nasal dorsum. Biological grafts or alloplastic materials are required to hurdle and correct nasal dorsal deformities and also irregularities. The purpose of this experimental study was to compare pure cartilage graft, cartilage graft wrapped in amniotic membrane, and diced cartilage grafts wrapped in amniotic membrane for soft tissue augmentation. METHODS: All grafts were transplanted through a subcutaneous tunnel created in the nasal dorsum of 18 rats, 6 in each group. After 3 months follow-up, the histopathological changes in all groups were evaluated by light microscopy and volumetric measurements. RESULTS: With regard to cartilage viability, cartilage wrapped in amniotic membrane had a higher success rate than pure cartilage graft. Also, a further increased success rate was found in the diced group. CONCLUSIONS: In the soft tissue augmentation after rhinoplasty surgery, especially diced cartilage wrapped in amniotic membrane keeps the graft viable and adjoined. PMID- 27192645 TI - Which Patients With Ossifying Fibroma of the Jaws Would Be Suitable for Radical Ablative Surgery? AB - OBJECTIVE: The aim of authors' study was to present their 10-year experience in the treatment of giant ossifying fibroma (GOF), and to prove if GOF can be totally excised preventing recurrence. The authors' secondary goal was to study the aesthetic and functional outcomes after radical resection of GOF followed by immediate reconstruction. METHODS: Eighteen patients who underwent radical ablative surgery of GOF of the jaw followed by immediate reconstruction with vascularized fibula flap or ilium flap between May 2003 and May 2013 were taken. Recurrence rate was statistically observed and 2-year postoperative aesthetic and functional outcomes were evaluated. RESULTS: The average length of follow-up was 4.5 years. There was no residual tumor or tumor recurrence observed in any patient during the mean follow-up of 4.5 years, and good cosmesis and functional outcome was noted after ablative surgery of GOF followed by computer-assisted reconstruction. CONCLUSIONS: For giant OF, if it is mainly located in the jaws without invasion of the skull base and/or pterygoid process, radical surgical treatment should be performed for prevention of tumor recurrence. And good aesthetic and functional results can be achieved by immediate computer-assisted reconstruction and dental rehabilitation. PMID- 27192646 TI - A New Technique for Posterior Distraction in Craniosynostosis: The Double-Door Technique. AB - BACKGROUND: Posterior cranial vault distraction osteogenesis is a common treatment for syndromal patients of brachycephaly and oxycephaly. Although posterior distraction can increase intracranial volume, the flattened head phenotype is difficult to correct. The authors examined a new posterior distraction technique termed double-door distraction for improvement of the flattened head phenotype. METHODS: From 2010 to 2013, 6 patients with flattened posterior craniums were operated on using the double-door distraction technique. The calvarial segment was cut at the midline and divided into 2 pieces. Distractors were then fixed in parallel to join the calvarial pieces. The distraction was initiated at a rate of 1.0 mm/day and continued until proper cranial form was confirmed by radiography and appearance. RESULTS: The average surgery time was 2 hours 47 minutes and the amount of distraction ranged from 15 to 22 mm. An improved head shape and expanded cranial vault was achieved in all patients without any complications. CONCLUSIONS: The double-door distraction technique is a useful technique not only for calvarial expansion, but also for correction of the flattened posterior cranium phenotype. PMID- 27192648 TI - The Retromolar Trigone: Anatomy, Cancer Treatment Modalities, Reconstruction, and a Classification System. AB - BACKGROUND: Retromolar trigone (RMT) tumors are rare and aggressive malignancies, spreading rapidly into surrounding structures. In reviewing the literature, there is lack of information and quality evidence pertaining to their management and high heterogeneity in treatment modalities. METHODS: A systematic Medline search was performed to gather all reports of articles related to retromolar trigone in tle last 10 years (2005-2015). Papers were excluded if they were related to oral cavity cancer but not specific for the RMT. RESULTS: Results were divided into 5 sections: anatomy and lymphatic drainage; etiology and diagnosis; cancer treatment modalities; reconstructive options; proposal of a classifications system. A clinical patient exemplification was also included. Various treatment modalities have been tried in the past including surgery, radiotherapy, and combination therapy using chemoradiation. All these modalities have intrinsic risks. There is also controversy regarding the extent of surgery. Reconstructive options differ with the size of the defects. The ability of the propeller lingual flap to rotate any angle up to 180 degrees allows it to reconstruct small-to medium sized defects. If bulkier reconstructions are needed to separate oral and nasal cavities, a free flap (radial forearm, anterolateral thigh, medial sural) should be planned. CONCLUSIONS: In view of the rarity of the tumor and heterogeneity of treatment, there is limited information available pertaining to retromolar trigone tumors. A better understanding of RMT amatomy, cancer treatment modalities, and reconstructive options can improve the surgeon decision capacity and clinical results, when dealing with such uncommon and challenging tumors. PMID- 27192647 TI - Survival Without Neurological Impairment of a Patient With Rhino-Orbito-Cerebral Zygomycosis. AB - Rhinocerebral zygomycosis is a rare condition characterized by infection initially in the nose and paranasal sinuses with atypical symptoms consistent with sinusitis. Once established in the nasal sinuses, the infection can easily spread to the orbital region and brain. In the localized form of the infection, the mortality rate is approximately 10%, which increases in the occurrence of orbital involvement and survival in patients of cerebral dissemination is extremely rare. The present paper reports a patient of nasal zygomycosis with orbital and cerebral dissemination in an otherwise healthy patient who survived after 14 months of hospitalization with no neurological impairment. A review of the literature addressing aspects related to diagnosis, treatment, and complications of this fungal infection is also presented. PMID- 27192649 TI - Delayed Onset Intracranial Subdural Hematoma Following Spinal Surgery. AB - In this case-based review, the authors analyzed relevant literature with an illustrative patient of theirs about subdural hematoma secondary to dural tear at spinal surgery. Intracranial hypotension is a condition of decreased cerebrospinal fluid volume and pressure. Even though intracranial hypotension is temporary and can be managed conservatively, it may progress and result in subdural fluid collections, hematoma formations, "brain sagging or slumping" states, syringohydromyelia, encephalopathy, coma, and even death. The authors present an 81-year-old man admitted with subdural hematoma 50 days following previous spinal surgery for lumbar spinal stenosis. In his previous spinal surgery he had had dural tear, which had been closed primarily. To the literature, only 21 patients have been reported to develop subdural hematoma following spinal surgery. In patients with subdural hematoma following spinal surgery, the female:male ratio was 3:4 and the median age was 55 years. Surgical diagnoses for previous spinal surgeries were intervertebral disc herniation (5), spinal canal stenosis and spondylolisthesis (6), failed back syndrome (2), tethered cord syndrome and myelodysplastic spine (2), spinal cord tumor, spinal epidural hematoma, vertebral dislocation, vertebral fracture, vertebral tumor, and inflammatory spine. Patients presented with signs and symptoms of subdural hematoma within 6 hours to 50 days following the spinal surgery. Source of cerebrospinal fluid leak was most commonly from lumbar region (13 patients, 62%). Ten of 21 (48%) patients were treated conservatively. Late-onset neurological findings should not prevent the evaluation of cranial vault with computed tomography and magnetic resonance imaging. Spinal dural tear should be more aggressively treated instead of suture alone approach, when recognized in older patients during the spinal surgery. PMID- 27192650 TI - A Patient With Aspiration Pneumonia After Mandibular Osteotomy With Genioplasty. AB - Orthognathic surgery including maxillary osteotomy, mandibular osteotomy, and genioplasty is a reliable treatment strategy for jaw deformity. However, there are some complications associated with these surgeries, including neurovascular damage and abnormal bleeding. The authors present here a patient of aspiration pneumonia after mandibular osteotomy.An 18-year-old female patient underwent sagittal split ramus osteotomy and genioplasty for mandibular prognathism. She began choking and coughing immediately after surgery. She was diagnosed with aspiration pneumonia based on chest radiography and computed tomography findings. Her hyoid bone was shifted 23 mm inferiorly after surgery, and this movement may have caused swallowing dysfunction. She was treated with intravenous antibiotics and discharged on the 18th postoperative day.Although the hyoid bone is transiently shifted inferiorly by mandibular setback with or without genioplasty, this shift does not usually affect swallowing function. Damage to the suprahyoid muscles during genioplasty may cause both an inferior shift and dysmobility of the hyoid bone. Therefore, surgeons must be careful not to damage the suprahyoid muscles at the lingual site osteotomy in genioplasty to avoid this complication. PMID- 27192652 TI - Preservation of Facial Nerve With Adjuvant Radiotherapy for Recurrent Mammary Analogue Secretory Carcinoma of Parotid Gland. AB - Mammary analogue secretory carcinoma of salivary glands harbors the recurrent ETV6-NTRK3 gene fusion because of the translocation t (12; 15) (p13; q25) and resembles breast secretory carcinoma. This tumor composed of papillary, cystic, solid, and cribriform patterns. Immunohistochemically, the tumors are positive for mammaglobin, CK7, CK8, STAT5a, vimentin, and S100. In this report, the authors presented a patient of recurrent parotid gland mammary analogue secretory carcinoma in a 22-year-old woman. The patient received extended parotidectomy with partial adhesive masseter surgery. The facial nerve was preserved during the surgery and adjuvant radiotherapy was performed postoperation. The patient did not suffer local recurrence and facial paralysis in the 18 months follow-up period. PMID- 27192651 TI - Considerations for Management of Head and Neck Lymphatic Malformations in Children. AB - OBJECTIVE: There exist inherent problems with previously described classification schemes for head and neck lymphatic malformations in children and lack of guidance for management. An organization scheme and management recommendations are proposed to improve communication between health care providers. STUDY DESIGN: Consecutive patient series with a chart review of children with head and neck lymphatic malformations. SETTING: Tertiary-care, academic children's hospital. METHODS: Children with lymphatic malformations of the head and neck were included. A proposed organization system for head and neck lymphatic malformations in children was developed and compared to 2 others currently predominantly used, de Serres and Cologne Disease Score. RESULTS: Seventeen patients were identified, 7 boys and 10 girls. The mean age was 64.4 months (range 0.89-185.5). Nine patients (52.9%) were managed expectantly, 5 (29.4%) with sclerotherapy with 1 awaiting treatment (5.9%), and 2 (11.8%) with surgical excision. All children who underwent active treatment with surgery or sclerotherapy were managed successfully. No treatment-related complications were encountered, and no children managed with watchful waiting/expectant management experienced failure. The proposed staging system differed from the de Serres stage in 11 children (64.7%), with 9 (81.8%) being down staged and 2 (18.2%) up staged. Cologne Disease Score ranged from 2 to 10, with only 1 (5.9%) patient with a score of 3 or less (severe disease). CONCLUSIONS: Treatment recommendations in children with head and neck lymphatic malformations should be individualized. Weaknesses of currently used staging systems are discussed as well as considerations for management decisions. PMID- 27192653 TI - Extensive Chondrosarcoma of the Nasal Septum: Endoscopic Resection and Long-Term Follow-Up. AB - Chondrosarcoma of the nasal septum is extremely rare slow growing malignant tumor of nonepithelial origin. Preoperative differentiation between low-grade chondrosarcoma and benign cartilaginous tumors such as chondroma may be difficult. Surgical excision is the treatment of choice. Radiotherapy is reserved for residual or recurrent patients. Recent advance in endoscopic sinus surgery has allowed successful, noninvasive excision of many sinonasal tumors with low morbidity.The authors herein report, what we believe, the most extensive case of posterior nasal septal chondrosarcoma with the longest follow-up period that was completely excised endoscopically with no evidence of local or systemic recurrence after 5 years. The authors also discuss its relevant clinical presentation, diagnosis, and management. PMID- 27192655 TI - Pathologic Patency Analysis of the Descending Branch of the Lateral Femoral Circumflex Artery in Head and Neck Reconstruction. AB - The pathophysiology of atherosclerotic lesion progression shows that the composition of an atherosclerotic lesion is related to the clinical status of the patient. In humans, certain artery types, such as the coronary artery, renal artery, and internal carotid artery at the level of the carotid sinus and aorta, are prone to develop clinically manifested atherosclerosis, whereas other artery types remain free of atherosclerotic disease. In head and neck reconstruction, various flaps are used. Especially, anterolateral thigh free flap is a good option for reconstruction. The descending branch of the lateral femoral circumflex artery (DLFCA) is useful as an alternative arterial graft and pedicle for anterolateral thigh flaps. However, no pathophysiological study has determined whether the DLFCA is atherosclerosis resistant. The authors studied the morphological characteristics of the DLFCA and assessed the correlation with the degree of atherosclerotic change. Seventeen perforators originating from the DLFCA were selected. All sections were classified into 6 lesion types according to the American Heart Association. Seven sections contained a stenotic area of at least 25% and 1 section was > 50%. All sections were classified as type 1. In conclusion, the DLFCA only has physiological adaptation in the intimal layer and no relationship with atherosclerotic risk factors. Therefore, the DLFCA is atherosclerosis resistant and surgeons should not hesitate to use the DLFCA. PMID- 27192654 TI - Assessing the Cervical Range of Motion in Infants With Positional Plagiocephaly. AB - PURPOSE: To determine if infants with positional plagiocephaly have limitations of active and passive cervical range of motion measured with simple and reliable methods. METHODS: The examiners assessed bilateral active and passive cervical rotations and passive cervical lateral flexion. Cervical assessment was performed twice by 2 different physicians to assess intertester reliability. To assess intratester reliability the first investigator performed a second examination 48 hours after the first one. RESULTS: One-hundred nine subjects were analyzed; 70.7% of the sample had head positional preference on the right, while 29.3% had head positional preference on the left (chi 35.52, P <0.001). Cervical rotations and lateral flexion showed reliable levels of agreement for intra and intertester reliability. CONCLUSIONS: The most limited range of motion in infants with positional plagiocephaly was cervical active rotation which affected more than 90% of patients. Passive cervical rotations and lateral flexion were limited in more than 60% of patients. PMID- 27192656 TI - Parental Perceptions of Neurodevelopment in Toddlers Following Craniosynostosis Repair. AB - INTRODUCTION: The relationship between nonsyndromic craniosynostosis and neurodevelopment remains controversial. Beyond standardized testing, little data exist about parental perceptions of their child's development. METHODS: Parents of children who underwent cranial vault remodeling for nonsyndromic craniosynostosis from 2011 to 2015 were asked to complete an anonymous survey. RESULTS: Twenty-two parents (31%) completed the survey. Patients included 52.4% males and 47.6% females with a mean age at surgery of 9.2 months and mean follow up time of 19.8 months. Craniosynostosis types were primarily metopic (45%) and coronal (35%).The mean score for overall satisfaction with head shape with a maximum score of 10 was 9.2 (range 5-10). When answering whether their child is different for the better other than appearance with a 5 rating as "strongly agree," the mean score was 3.8 (range 1-5). When asked whether their child's motor, speech and behavior, or attention were different following surgery, the majority responded "No" (74%, 83%, and 67%, respectively).All parents would have their child undergo surgery again or recommend surgery to another family. There were no statistically significant differences when stratifying by age at surgery or length of follow-up. When stratifying by sex, parents of males gave higher ratings for whether their children were better other than appearance compared with females, 4.8 versus 3.1 (P = 0.031). DISCUSSION: Parents rated their child's neurodevelopment as largely age-appropriate following cranial vault remodeling. These findings are concordant with the majority of formal, standardized testing for this age group. Assessing parental perceptions once children enter school age may reveal increased developmental delays. PMID- 27192657 TI - Sternal Wound Salvage in Post-Transplant Adolescents: Omental Flap Reconstruction in Patients With Prior Abdominal Surgery. AB - Sternal wound infections remain a significant cause of morbidity and mortality in patients undergoing complex cardiothoracic surgery. Heart and lung transplant patients presumably face additional risk secondary to their underlying morbidity, postoperative immunosuppression, and difficulty with primary wound closure over large graft size. These patients present a unique challenge to the reconstructive surgeon, as many have a significant past surgical history, which can limit or alter treatment options. This study reports 2 pediatric transplant patients who underwent use of omental flap for sternal wound reconstruction in the context of significant past abdominal surgery. One patient underwent prior heart transplantation and the other patient underwent previous bilateral lung transplantation. Both had significant abdominal surgery prior to transplantation and suffered from sternal wound complications post-transplantation. Each patient was successfully treated with omental flap reconstruction. PMID- 27192658 TI - Multiple Human Papilloma Virus 16 Infection Presenting as Various Skin Lesions. AB - The 53-year-old woman admitted with multiple persistent, progressive, slightly raised, red, and crusted plague form masses that suddenly occurred on left thumb, both upper and lower extremity about 10 years ago. There was no induration in the lesion or in its surrounding skin. There was no unusual opinion on a radiologic test and family history. And she had no history of working in the business related to any chemical product such as arsenic or tar which was carcinogen. The patient has had total hysterectomy to treat uterine myoma 10 years ago. The wide excision and split thickness skin graft of 2 * 1.5 cm was performed around mass in the size of 1.5 * 1.2 cm on the left thumb and wide excision and local advancement flap was done on the other sites. As a result of biopsy, masses were diagnosed as Bowen disease, actinic keratosis, and Seborrheic keratosis. These specimens were obtained during surgery: broom-type cell sampling devices were used to collect samples from the specimens, and they were placed into PreservCyt solution (Cytyc Corp, Boxborough, MA). Then, the collected samples underwent the Roche Linear Array HPV Genotyping Test (Roche Diagnostics, Branchburg, NJ) that allows for the simultaneous identification of human papilloma virus (HPV) types from liquid-based cell preparations. On histopathological examination of the surgical specimen, atypical squamous cells proliferate through the whole thickness of the epidermis. The entire tumor was confined to the epidermis and did not invade into the dermis. The cells were often highly atypical. That were the irregular shape which the resection margin of masses had a negative tumor component. And HPV 16 genotyping test was positive although vaginal examination of HPV 16 genotyping was negative. PMID- 27192660 TI - Estimating the average treatment effect on survival based on observational data and using partly conditional modeling. AB - Treatments are frequently evaluated in terms of their effect on patient survival. In settings where randomization of treatment is not feasible, observational data are employed, necessitating correction for covariate imbalances. Treatments are usually compared using a hazard ratio. Most existing methods which quantify the treatment effect through the survival function are applicable to treatments assigned at time 0. In the data structure of our interest, subjects typically begin follow-up untreated; time-until-treatment, and the pretreatment death hazard are both heavily influenced by longitudinal covariates; and subjects may experience periods of treatment ineligibility. We propose semiparametric methods for estimating the average difference in restricted mean survival time attributable to a time-dependent treatment, the average effect of treatment among the treated, under current treatment assignment patterns. The pre- and posttreatment models are partly conditional, in that they use the covariate history up to the time of treatment. The pre-treatment model is estimated through recently developed landmark analysis methods. For each treated patient, fitted pre- and posttreatment survival curves are projected out, then averaged in a manner which accounts for the censoring of treatment times. Asymptotic properties are derived and evaluated through simulation. The proposed methods are applied to liver transplant data in order to estimate the effect of liver transplantation on survival among transplant recipients under current practice patterns. PMID- 27192659 TI - Clinical activity of sunitinib rechallenge in metastatic renal cell carcinoma Results of the REchallenge with SUnitinib in MEtastatic RCC (RESUME) Study. AB - AIM: To assess the efficacy and tolerability of sunitinib rechallenge in the third-line or later setting in patients with metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: This observational study comprised 61 mRCC patients at 19 centres in France who received sunitinib rechallenge between January 2006 and May 2013. Patients received first-line sunitinib, >=1 different targeted therapies, and then sunitinib rechallenge. Patient/disease characteristics, tolerability, treatment modalities, and outcomes of therapeutic lines were recorded. The primary end-point was progression-free survival (PFS) in sunitinib rechallenge. RESULTS: Analyses included 52 patients; median age was 59 years, 75% were male, and 98% had clear-cell mRCC and prior nephrectomy. At sunitinib rechallenge versus first-line, patients had poorer performance (Karnofsky performance status 90-100: 30% versus 81%) and Memorial Sloan Kettering Cancer Centre prognostic risk (poor risk: 18% versus 3%). Overall, 20%, 65%, 12%, and 4% received sunitinib rechallenge as third-, fourth-, fifth-, and sixth-line therapy, respectively, at 14.6 months (median) after stopping initial treatment. With first-line sunitinib and rechallenge, median PFS was 18.4 and 7.9 months, respectively; objective response rate was 54% and 15%. Two of eight rechallenge responders had not achieved first-line response. Median overall survival was 55.9 months. The sunitinib rechallenge safety profile was as expected, with no new adverse events reported. CONCLUSIONS: Sunitinib rechallenge is a feasible treatment option with potential clinical benefit for mRCC patients. Disease progression with first-line sunitinib may not be associated with complete or irreversible resistance to therapy. PMID- 27192661 TI - The Greek version of the Gagging Assessment Scale in children and adolescents: psychometric properties, prevalence of gagging, and the association between gagging and dental fear. AB - BACKGROUND: No studies assessing the association between gagging and dental fear are available in pediatric samples. AIM: To assess the psychometric properties of the Greek version of the Gagging Assessment Scale (GAS), to explore the prevalence of gagging, and to evaluate the relationship between gagging and dental fear in a pediatric sample. DESIGN: A total of 849 8- and 14-year-old children filled out a questionnaire consisting of demographic items, the Greek version of the GAS, and the Greek Children's Fear Survey Schedule Dental Subscale (CFSS-DS); the older children also completed the Greek version of the Modified Dental Anxiety Scale (MDAS). The short form of dentist part of the Gagging Problem Assessment (GPA-de-c/SF) was used to objectively assess gagging. RESULTS: A total of 51 children (6.0%) demonstrated gagging on the GPA-de-c/SF. Children rated as gaggers on the GPA-de-c/SF had significantly higher GAS scores. There were no relationships between GPA-de-c/SF and the CFSS-DS or MDAS. The GAS ratings were significantly correlated with the CFSS-DS (rho = 0.420, P < 0.001) and MDAS (rho = 0.429, P < 0.001). The internal consistency was good (Cronbach's alpha = 0.697). CONCLUSIONS: The GAS demonstrated good psychometric properties. Dental fear was correlated with the self-report gagging assessment, but not with the objective gagging assessment. PMID- 27192662 TI - Effect of System-Wide Interventions on the Assessment and Treatment of Pain by Emergency Medical Services Providers. AB - BACKGROUND: An estimated 20% of patients arriving by ambulance to the emergency department are in moderate to severe pain. However, the management of pain in the prehospital setting has been shown to be inadequate. Untreated pain may have negative physiologic and psychological consequences. The prehospital community has acknowledged this inadequacy and made treatment of pain a priority. OBJECTIVES: To determine if system-wide pain management improvement efforts (i.e. education and protocol implementation) improve the assessment of pain and treatment with opioid medications in the prehospital setting and to determine if improvements are maintained over time. METHODS: This was a retrospective before and after study of a countywide prehospital patient care database. The study population included all adult patients transported by EMS between February 2004 and February 2012 with a working assessment of trauma or burn. EMS patient care records were searched for documentation of pain scores and opioid administration. Four time periods were examined: 1) before interventions, 2) after pediatric specific pain management education, 3) after pain management protocol implementation, and 4) maintenance phase. Frequencies and 95% confidence intervals were calculated for all patients meeting the inclusion criteria in each time period and Chi-square was used to compare frequencies between time periods. RESULTS: 15,228 adult patients transported by EMS during the study period met the inclusion criteria. Subject demographics were similar between the four time periods. Pain score documentation improved between the time periods but was not maintained over time (13% [95%CI 12-15%] to 32% [95%CI 31-34%] to 29% [95 CI 27 30%] to 19% [95%CI 18-21%]). Opioid administration also improved between the time periods and was maintained over time (7% [95%CI 6-8%] to 18% [95%CI 16-19%] to 24% [95%CI 22-25%] to 23% [95% CI 22-24%]). CONCLUSIONS: In adult patients both pediatric-focused education and pain protocol implementation improved the administration of opioid pain medications. Documentation and assessment of pain scores was less affected by specific pain management improvement efforts. PMID- 27192663 TI - De Laboratoria Van Klinische Biologie in Belgie: Evolutie En Situatie Na Organisatie Van De Verpl1Chte Externe KWaliteitscontrole. AB - The evolution and the situation of the laboratories of clinical biology in Belgium is described. This paper gives a point of view of the locality, the activity and the employment in these laboratories. PMID- 27192664 TI - The Epidemiology of Chronic Digestive Disease. PMID- 27192665 TI - The effects of low voltage electrical stimulation on donkey meat. PMID- 27192666 TI - Disparities in Academic Dermatology. PMID- 27192667 TI - Crystal structure of a [NiFe] hydrogenase maturation protease HybD from Thermococcus kodakarensis KOD1. AB - A [NiFe] hydrogenase maturation protease HybD from Thermococcus kodakarensis KOD1 (TkHybD) is involved in the cleavage of the C-terminal residues of [NiFe] hydrogenase large subunits by Ni recognition. Here, we report the crystal structure of TkHybD at 1.82 A resolution to better understand this process. TkHybD exhibits an alpha/beta/alpha sandwich fold with conserved residues responsible for the Ni recognition. Comparisons of TkHybD with homologous proteins also reveal that they share a common overall architecture, suggesting that they have similar catalytic functions. Our results including metal binding site prediction provide insight into the substrate recognition and catalysis mechanism of TkHybD. Proteins 2016; 84:1321-1327. (c) 2016 Wiley Periodicals, Inc. PMID- 27192668 TI - Matrix-assisted laser desorption ionization-time of flight Mass spectrometry can detect Staphylococcus aureus clonal complex 398. AB - Within the last decade methicillin-resistant Staphylococcus aureus belonging to CC398 has become a worldwide threat associated with livestock. More recently, methicillin-susceptible S. aureus (MSSA) belonging to CC398 have been increasingly reported as a cause of invasive infections in patients without livestock contact. It appears therefore necessary to implement a convenient tool for the surveillance this emerging pathogen. We evaluated the MALDI-TOF MS as a tool for rapid detection of S. aureus CC398. We used 626 S. aureus isolates characterized by a CC398-specific PCR, to constitute independent training (300 isolates including 60 isolates CC398) and validation sets (326 isolates including 82 isolates CC398). Fifteen peak biomarkers of CC398 were identified from the mass spectra of the training set. Ninety four % (307 of 326) of strains of the validation set were well assigned with an overall sensitivity of 93% and a specificity of 95%. Six CC398 and 13 non-CC398 isolates were misclassified. With MALDI-TOF MS, clinical laboratories could rapidly detect S. aureus CC398 associated with a higher mortality in hospitalized patients. PMID- 27192669 TI - Essential Medicines in the United States--Why Access Is Diminishing. PMID- 27192670 TI - The Great War and Modern Health Care. PMID- 27192673 TI - Coronary-Artery Bypass Grafting. PMID- 27192671 TI - Danazol Treatment for Telomere Diseases. AB - BACKGROUND: Genetic defects in telomere maintenance and repair cause bone marrow failure, liver cirrhosis, and pulmonary fibrosis, and they increase susceptibility to cancer. Historically, androgens have been useful as treatment for marrow failure syndromes. In tissue culture and animal models, sex hormones regulate expression of the telomerase gene. METHODS: In a phase 1-2 prospective study involving patients with telomere diseases, we administered the synthetic sex hormone danazol orally at a dose of 800 mg per day for a total of 24 months. The goal of treatment was the attenuation of accelerated telomere attrition, and the primary efficacy end point was a 20% reduction in the annual rate of telomere attrition measured at 24 months. The occurrence of toxic effects of treatment was the primary safety end point. Hematologic response to treatment at various time points was the secondary efficacy end point. RESULTS: After 27 patients were enrolled, the study was halted early, because telomere attrition was reduced in all 12 patients who could be evaluated for the primary end point; in the intention-to-treat analysis, 12 of 27 patients (44%; 95% confidence interval [CI], 26 to 64) met the primary efficacy end point. Unexpectedly, almost all the patients (11 of 12, 92%) had a gain in telomere length at 24 months as compared with baseline (mean increase, 386 bp [95% CI, 178 to 593]); in exploratory analyses, similar increases were observed at 6 months (16 of 21 patients; mean increase, 175 bp [95% CI, 79 to 271]) and 12 months (16 of 18 patients; mean increase, 360 bp [95% CI, 209 to 512]). Hematologic responses occurred in 19 of 24 patients (79%) who could be evaluated at 3 months and in 10 of 12 patients (83%) who could be evaluated at 24 months. Known adverse effects of danazol- elevated liver-enzyme levels and muscle cramps--of grade 2 or less occurred in 41% and 33% of the patients, respectively. CONCLUSIONS: In our study, treatment with danazol led to telomere elongation in patients with telomere diseases. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01441037.). PMID- 27192674 TI - IMAGES IN CLINICAL MEDICINE. Splenosis Mimicking Cancer. PMID- 27192672 TI - Randomized Trial of a Lifestyle Program in Obese Infertile Women. AB - BACKGROUND: Small lifestyle-intervention studies suggest that modest weight loss increases the chance of conception and may improve perinatal outcomes, but large randomized, controlled trials are lacking. METHODS: We randomly assigned infertile women with a body-mass index (the weight in kilograms divided by the square of the height in meters) of 29 or higher to a 6-month lifestyle intervention preceding treatment for infertility or to prompt treatment for infertility. The primary outcome was the vaginal birth of a healthy singleton at term within 24 months after randomization. RESULTS: We assigned women who did not conceive naturally to one of two treatment strategies: 290 women were assigned to a 6-month lifestyle-intervention program preceding 18 months of infertility treatment (intervention group) and 287 were assigned to prompt infertility treatment for 24 months (control group). A total of 3 women withdrew consent, so 289 women in the intervention group and 285 women in the control group were included in the analysis. The discontinuation rate in the intervention group was 21.8%. In intention-to-treat analyses, the mean weight loss was 4.4 kg in the intervention group and 1.1 kg in the control group (P<0.001). The primary outcome occurred in 27.1% of the women in the intervention group and 35.2% of those in the control group (rate ratio in the intervention group, 0.77; 95% confidence interval, 0.60 to 0.99). CONCLUSIONS: In obese infertile women, a lifestyle intervention preceding infertility treatment, as compared with prompt infertility treatment, did not result in higher rates of a vaginal birth of a healthy singleton at term within 24 months after randomization. (Funded by the Netherlands Organization for Health Research and Development; Netherlands Trial Register number, NTR1530.). PMID- 27192675 TI - CASE RECORDS of the MASSACHUSETTS GENERAL HOSPITAL. Case 15-2016. A 32-Year-Old Man with Olfactory Hallucinations and Paresthesias. PMID- 27192676 TI - Is Less More for the Treatment of Atrial Fibrillation after Cardiac Surgery? PMID- 27192677 TI - Telomeres on Steroids--Turning Back the Mitotic Clock? PMID- 27192678 TI - Weight Loss and Health Status after Bariatric Surgery in Adolescents. PMID- 27192679 TI - Weight Loss and Health Status after Bariatric Surgery in Adolescents. PMID- 27192680 TI - Weight Loss and Health Status after Bariatric Surgery in Adolescents. PMID- 27192681 TI - Weight Loss and Health Status after Bariatric Surgery in Adolescents. PMID- 27192682 TI - Papillary Renal-Cell Carcinoma. PMID- 27192683 TI - Papillary Renal-Cell Carcinoma. PMID- 27192684 TI - Surgery for Severe Ischemic Mitral Regurgitation. PMID- 27192685 TI - Surgery for Severe Ischemic Mitral Regurgitation. PMID- 27192686 TI - Surgery for Severe Ischemic Mitral Regurgitation. PMID- 27192687 TI - Medical Taylorism, Lean, and Toyota. PMID- 27192688 TI - Medical Taylorism, Lean, and Toyota. PMID- 27192689 TI - Medical Taylorism, Lean, and Toyota. PMID- 27192690 TI - A Mechanism for Cancer-Associated Membranous Nephropathy. PMID- 27192691 TI - IMAGES IN CLINICAL MEDICINE. Loose Teeth and Excessive Thirst. PMID- 27192692 TI - Concise Approach to (ent)-14 beta-Hydroxysteroids through Highly Diastereo /Enantioselective Diels-Alder Reactions. AB - 14beta-Hydroxysteroids, especially 14beta-hydroxyandrostane derivatives are closely related to the cardenolide skeletons. The latter were readily available through highly diastero/enantioselective Diels-Alder (DA) reactions requiring high pressure or Lewis acid activation. Moreover, in the presence of (R)- or (S) carvone as a chiral dienophile, the DA-reaction takes place under chemodivergent parallel kinetic resolution control affording highly enantiomerically enriched 14beta-hydroxysteroid derivatives or the corresponding (ent)-14beta hydroxysteroid derivatives. PMID- 27192693 TI - Use of controlled internal drug releasing (CIDR) devices to control reproduction in goats: A review. AB - High reproductive rates are necessary in order to increase the productivity of goat operations. Progesterone and its analogues are widely used in other species to control the reproductive system to facilitate synchronized births, induce fertile estrus or to facilitate the use of assisted reproductive techniques with the goal of increasing productivity of livestock. Progesterone impregnated controlled internal drug releasing (CIDR) devices are approved for delivery of the natural hormone progesterone to synchronize and induce fertile estrus in sheep. A few studies have reported a high estrous response and pregnancy rates when CIDRs are used to induce estrus in goats. However, significant variation exists in the duration of treatment (5-16 days) and in the use of exogenous gonadotropins as part of the treatment protocol. As gonadotropins are not currently approved for commercial use in small ruminants in the USA, studies are needed to determine the necessity for exogenous gonadotropins and whether they can be replaced by enhancing endogenous secretion through photoperiodic manipulation of the doe and ? or increase stimulation through the 'buck-effect'. Future studies must not only evaluate efficacy, but should consider the economic feasibility of using CIDRs in commercial production systems. PMID- 27192694 TI - Differences of brain electrical activity between moderate and severe obstructive sleep apneic patients: a LORETA study. AB - The effects of initiation of continuous positive airway pressure (CPAP) therapy on electroencephalographic (EEG) background activity were investigated in patients exhibiting both moderate (n = 13) and severe (n = 12) obstructive sleep apnea syndromes in the testing of the potential differences of alterations of brain electrical activity caused by chronic hypoxia between these two groups. A normal control group (n = 14) was also examined. Two EEG examinations were achieved in each group: before and after first-time CPAP therapy. Low-resolution electromagnetic tomography (LORETA) was implemented towards localizing the generators of EEG activity in separate frequency bands. Prior to CPAP treatment, as a common direction of change, analysis with LORETA demonstrated increased activity in comparison with the patient and control groups. In the moderate group, significant changes were detected in the alpha2 band in the posterior cingulate cortex as well as in the beta1 band in the right posterior parietal cortex and the left supramarginal gyrus. In the severe group, significant changes were found in theta and alpha1 bands in the posterior cingulate cortex. Following CPAP treatment, these significant differences vanished in the severe group. In the moderate group, significantly decreased activity was seen in the beta3 band in the right fusiform gyrus. These findings potentially suggest a normalizing effect of CPAP therapy on EEG background activity in both groups of obstructive sleep apnea syndrome patients. Compensatory alterations of brain electrical activity in regions associated with influencing successful memory retrieval, emotional perception, default mode network, anorexia and fear network caused by chronic intermittent hypoxia could possibly be reversed with the use of CPAP therapy. PMID- 27192695 TI - Increased F3-Isoprostanes in the Canadian Inuit Population Could Be Cardioprotective by Limiting F2-Isoprostane Production. AB - CONTEXT: F3-isoprostanes (F3-IsoPs), derived from peroxidation of eicosapentaenoic acid (C20:5n-3), could be cardioprotective by limiting production of F2-isoprostanes (F2-IsoPs), a cardiovascular disease risk factor. OBJECTIVE: The objective of the study was to determine whether the n-3 polyunsaturated (PUFA)-rich Inuit diet is associated with a lower plasma ratio of F2-IsoPs to F3-IsoPs. DESIGN: This was a cross-sectional observational study. SETTING: The study was conducted in 36 Canadian Arctic Inuit communities. PARTICIPANTS: Participants included a random subset (n = 233) of Inuit adults taken from a population-based survey. MAIN OUTCOME MEASURES: Plasma F2-IsoPs and F3-IsoPs, cardiometabolic risk factors (blood lipids, C-reactive protein, blood pressure, fasting glucose) and markers of dietary exposure (erythrocyte n-3 and n 6 PUFA, blood levels of Se, mercury, polychlorinated biphenyls) were measured. RESULTS: Inuit aged 40 years old and older vs younger Inuit showed higher concentrations of plasma F3-IsoPs and erythrocyte n-3 PUFA and lower plasma F2 IsoPs concentrations despite having higher blood lipids, fasting glucose, systolic blood pressure, and percentage body fat. Plasma F3-IsoPs were not associated with any cardiometabolic measures. When subjects were categorized into tertiles according to total n-3 PUFA erythrocyte concentrations, F3-IsoPs increased with increasing tertiles, whereas the F2-IsoP to F3-IsoP ratio was lowest at the highest n-3 tertile. The F2-IsoP to F3-IsoP ratio was significantly predicted by C20:5n-3 (beta= -.365, P = .002); C20:4n-6:C20:5n-3 (beta = .056, P = .006), blood mercury (beta = -.812, P =.015), blood Se (beta = -1.95, P = .015), and smoking (beta = .745, P = .025). CONCLUSIONS: Plasma F3-IsoPs were not associated with cardiometabolic risk factors previously seen with F2-IsoPs. Higher n-3 fatty acid status was associated with lower plasma F2-IsoPs and higher plasma F3-IsoPs, which provides partial explanation to the cardioprotective effects of the n-3 PUFA-rich Inuit diet. PMID- 27192697 TI - Calcium-regulated import of myosin IC into the nucleus. AB - Myosin IC is a molecular motor involved in intracellular transport, cell motility, and transcription. Its mechanical properties are regulated by calcium via calmodulin binding, and its functions in the nucleus depend on import from the cytoplasm. The import has recently been shown to be mediated by the nuclear localization signal located within the calmodulin-binding domain. In the present paper, it is demonstrated that mutations in the calmodulin-binding sequence shift the intracellular distribution of myosin IC to the nucleus. The redistribution is displayed by isoform B, described originally as the "nuclear myosin," but is particularly pronounced with isoform C, the normally cytoplasmic isoform. Furthermore, experimental elevation of the intracellular calcium concentration induces a rapid import of myosin into the nucleus. The import is blocked by the importin beta inhibitor importazole. These findings are consistent with a mechanism whereby calmodulin binding prevents recognition of the nuclear localization sequence by importin beta, and the steric inhibition of import is released by cell signaling leading to the intracellular calcium elevation. The results establish a mechanistic connection between the calcium regulation of the motor function of myosin IC in the cytoplasm and the induction of its import into the nucleus. (c) 2016 Wiley Periodicals, Inc. PMID- 27192698 TI - Polq-Mediated End Joining Is Essential for Surviving DNA Double-Strand Breaks during Early Zebrafish Development. PMID- 27192696 TI - Effects of High-Dose Vitamin D2 Versus D3 on Total and Free 25-Hydroxyvitamin D and Markers of Calcium Balance. AB - CONTEXT: Controversy persists over: 1) how best to restore low serum 25 hydroxyvitamin D (25D) levels (vitamin D2 [D2] vs vitamin D3 [D3]); 2) how best to define vitamin D status (total [protein-bound + free] vs free 25D); and 3) how best to assess the bioactivity of free 25D. OBJECTIVE: To assess: 1) the effects of D2 vs D3 on serum total and free 25D; and 2) whether change in intact PTH (iPTH) is more strongly associated with change in total vs free 25D. DESIGN: Participants previously enrolled in a D2 vs D3 trial were matched for age, body mass index, and race/ethnicity. Participants received 50 000 IU of D2 or D3 twice weekly for 5 weeks, followed by a 5-week equilibration period. Biochemical assessment was performed at baseline and at 10 weeks. SETTING AND PARTICIPANTS: Thirty-eight adults (19 D2 and 19 D3) >=18 years of age with baseline 25D levels <30 ng/mL were recruited from an academic ambulatory osteoporosis clinic. OUTCOME MEASURES: Serum measures were total 25D, free 25D (directly measured), 1,25 dihydroxyvitamin D, calcium, and iPTH. Urine measure was fasting calcium:creatinine ratio. RESULTS: Baseline total (22.2 +/- 3.3 vs 23.3 +/- 7.2 ng/mL; P = .5) and free (5.4 +/- 0.8 vs 5.3 +/- 1.7 pg/mL; P = .8) 25D levels were similar between D2 and D3 groups. Increases in total (+27.6 vs +12.2 ng/mL; P = .001) and free (+3.6 vs +6.2 pg/mL; P = .02) 25D levels were greater with D3 vs D2. Percentage change in iPTH was significantly associated with change in free (but not total) 25D, without and with adjustment for supplementation regimen, change in 1,25-dihydroxyvitamin D, and change in calcium. CONCLUSIONS: D3 increased total and free 25D levels to a greater extent than D2. Free 25D may be superior to total 25D as a marker of vitamin D bioactivity. PMID- 27192699 TI - Enhanced removal of nitrate from water using amine-grafted agricultural wastes. AB - Adsorption using low-cost adsorbents is a favourable water treatment method for the removal of water contaminants. In this study the enhanced removal of nitrate, a contaminant at elevated concentration affecting human health and causing eutrophication of water, was tested using chemically modified agricultural wastes as adsorbents. Batch and fixed-bed adsorption studies were performed on corn cob and coconut copra that were surface modified by amine-grafting to increase the surface positive charges. The Langmuir nitrate adsorption capacities (mgN/g) were 49.9 and 59.0 for the amine-grafted (AG) corn cob and coconut copra, respectively at pH6.5 and ionic strength 1*10(-3)M NaCl. These values are higher than those of many commercially available anion exchange resins. Fixed-bed (15-cm height) adsorption capacities (mgN/g) calculated from the breakthrough curves were 15.3 and 18.6 for AG corn cob and AG coconut copra, respectively, for an influent nitrate concentration 20mg N/L at a flow velocity 5m/h. Nitrate adsorption decreased in the presence of sulphate, phosphate and chloride, with sulphate being the most competitive anion. The Thomas model fitted well to the fixed-bed adsorption data from four repeated adsorption/desorption cycles. Plug-flow model fitted well to the data from only the first cycle. PMID- 27192700 TI - An evaluation of the migration of antimony from polyethylene terephthalate (PET) plastic used for bottled drinking water. AB - The leaching of antimony (Sb) from polyethylene terephthalate (PET) bottling material was assessed in twelve brands of bottled water purchased in Mexican supermarkets by atomic fluorescence spectrometry with a hydride generation system (HG-AFS). Dowex(r) 1X8-100 ion-exchange resin was used to preconcentrate trace amounts of Sb in water samples. Migration experiments from the PET bottle material were performed in water according to the following storage conditions: 1) temperature (25 and 75 degrees C), 2) pH (3 and 7) and 3) exposure time (5 and 15days), using ultrapure water as a simulant for liquid foods. The test conditions were studied by a 2(3) factorial experimental design. The Sb concentration measured in the PET packaging materials varied between 73.0 and 111.3mg/kg. The Sb concentration (0.28-2.30MUg/L) in all of the PET bottled drinking water samples examined at the initial stage of the study was below the maximum contaminant level of 5MUg/L prescribed by European Union (EU) regulations. The parameters studied (pH, temperature, and storage time) significantly affected the release of Sb, with temperature having the highest positive significant effect within the studied experimental domain. The highest Sb concentration leached from PET containers was in water samples at pH7 stored at 75 degrees C for a period of 5days. The extent of Sb leaching from the PET ingredients for different brands of drinking water can differ by as much as one order of magnitude in experiments conducted under the worst-case conditions. The chronic daily intake (CDI) caused by the release of Sb in one brand exceeded the Environmental Protection Agency (USEPA) regulated CDI value of 400ng/kg/day, with values of 514.3 and 566.2ng/kg/day for adults and children. Thus, the appropriate selection of the polymer used for the production of PET bottles seems to ensure low Sb levels in water samples. PMID- 27192701 TI - Acute strongyloidiasis in a traveller returning from South East Asia. AB - We report a case of acute strongyloidiasis, presenting with fever, pronounced eosinophilia and a disseminated skin rash, in a traveller returning from South East Asia. PMID- 27192705 TI - Strengthening the taxonomic backbone of Thai orchid conservation: genetic fingerprinting and morphometry applied to a species complex in Geodorum. AB - BACKGROUND AND AIMS: A well-supported classification is crucial for conservation planning, but intricate species complexes constitute a serious challenge to the preparation of flora accounts. In preparation of the Flora of Thailand account on Geodorum (Orchidaceae), it was decided to use multivariate morphometric analysis and genetic fingerprinting to resolve the intricate G. pulchellum sensu Seidenfaden/G. siamense species complex, with the specific aim of testing the taxonomic soundness of the apparently rare and conservation-requiring G. pulchellum sensu Seidenfaden. Geodorum densiflorum, universally considered distinct from the above species complex, was included as reference. METHODS: Morphometric data and tissue samples for amplified fragment length polymorphism (AFLP) analysis were collected from 17 Geodorum populations in northern and north eastern Thailand. Principal components analysis was employed to summarize the patterns of phenetic variation. Hierarchical genetic differentiation between populations was explored using Bayesian inference followed by cluster analysis. KEY RESULTS: The taxonomic distinction of G. densiflorum was generally supported. In contrast, G. siamense and G. pulchellum sensu Seidenfaden were poorly separated, especially according to the estimated patterns of inter-population genetic differentiation. CONCLUSIONS: The G. pulchellum sensu Seidenfaden/G. siamense complex should be treated as one variable species (under the name G. siamense), meaning that G. pulchellum sensu Seidenfaden should not be given high independent conservation priority. This study demonstrates that flora accounts can benefit from prior employment of multivariate and Bayesian methods for exploring intricate species complexes, in turn leading to more solid decisions and priorities in a conservation context. PMID- 27192706 TI - Low-temperature leaf photosynthesis of a Miscanthus germplasm collection correlates positively to shoot growth rate and specific leaf area. AB - BACKGROUND AND AIMS: The C4 perennial grass miscanthus has been found to be less sensitive to cold than most other C4 species, but still emerges later in spring than C3 species. Genotypic differences in miscanthus were investigated to identify genotypes with a high cold tolerance at low temperatures and quick recovery upon rising temperatures to enable them to exploit the early growing season in maritime cold climates. Suitable methods for field screening of cold tolerance in miscanthus were also identified. METHODS: Fourteen genotypes of M. sacchariflorus, M. sinensis, M. tinctorius and M. * giganteus were selected and grown under warm (24 degrees C) and cold (14 degrees C) conditions in a controlled environment. Dark-adapted chlorophyll fluorescence, specific leaf area (SLA) and net photosynthetic rate at a photosynthetically active radiation (PAR) of 1000 MUmol m(-2) s(-1) (A1000) were measured. Photosynthetic light and CO2 response curves were obtained from 11 of the genotypes, and shoot growth rate was measured under field conditions. KEY RESULTS: A positive linear relationship was found between SLA and light-saturated photosynthesis (Asat) across genotypes, and also between shoot growth rate under cool field conditions and A1000 at 14 degrees C in a climate chamber. When lowering the temperature from 24 to 14 degrees C, one M. sacchariflorus exhibited significantly higher Asat and maximum photosynthetic rate in the CO2 response curve (Vmax) than other genotypes at 14 degrees C, except M * giganteus 'Hornum'. Several genotypes returned to their pre chilling A1000 values when the temperature was increased to 24 degrees C after 24 d growth at 14 degrees C. CONCLUSIONS: One M. sacchariflorus genotype had similar or higher photosynthetic capacity than M * giganteus, and may be used for cultivation together with M * giganteus or for breeding new interspecies hybrids with improved traits for temperate climates. Two easily measured variables, SLA and shoot growth rate, may be useful for genotype screening of productivity and cold tolerance. PMID- 27192707 TI - Plant-plant interactions mediate the plastic and genotypic response of Plantago asiatica to CO2: an experiment with plant populations from naturally high CO2 areas. AB - BACKGROUND AND AIMS: The rising atmospheric CO2 concentration ([CO2]) is a ubiquitous selective force that may strongly impact species distribution and vegetation functioning. Plant-plant interactions could mediate the trajectory of vegetation responses to elevated [CO2], because some plants may benefit more from [CO2] elevation than others. The relative contribution of plastic (within the plant's lifetime) and genotypic (over several generations) responses to elevated [CO2] on plant performance was investigated and how these patterns are modified by plant-plant interactions was analysed. METHODS: Plantago asiatica seeds originating from natural CO2 springs and from ambient [CO2] sites were grown in mono stands of each one of the two origins as well as mixtures of both origins. In total, 1944 plants were grown in [CO2]-controlled walk-in climate rooms, under a [CO2] of 270, 450 and 750 ppm. A model was used for upscaling from leaf to whole-plant photosynthesis and for quantifying the influence of plastic and genotypic responses. KEY RESULTS: It was shown that changes in canopy photosynthesis, specific leaf area (SLA) and stomatal conductance in response to changes in growth [CO2] were mainly determined by plastic and not by genotypic responses. We further found that plants originating from high [CO2] habitats performed better in terms of whole-plant photosynthesis, biomass and leaf area, than those from ambient [CO2] habitats at elevated [CO2] only when both genotypes competed. Similarly, plants from ambient [CO2] habitats performed better at low [CO2], also only when both genotypes competed. No difference in performance was found in mono stands. CONCLUSION: The results indicate that natural selection under increasing [CO2] will be mainly driven by competitive interactions. This supports the notion that plant-plant interactions have an important influence on future vegetation functioning and species distribution. Furthermore, plant performance was mainly driven by plastic and not by genotypic responses to changes in atmospheric [CO2]. PMID- 27192708 TI - Repeated gains in yellow and anthocyanin pigmentation in flower colour transitions in the Antirrhineae. AB - BACKGROUND AND AIMS: Angiosperms display remarkable diversity in flower colour, implying that transitions between pigmentation phenotypes must have been common. Despite progress in understanding transitions between anthocyanin (blue, purple, pink or red) and unpigmented (white) flowers, little is known about the evolutionary patterns of flower-colour transitions in lineages with both yellow and anthocyanin-pigmented flowers. This study investigates the relative rates of evolutionary transitions between different combinations of yellow- and anthocyanin-pigmentation phenotypes in the tribe Antirrhineae. METHODS: We surveyed taxonomic literature for data on anthocyanin and yellow floral pigmentation for 369 species across the tribe. We then reconstructed the phylogeny of 169 taxa and used phylogenetic comparative methods to estimate transition rates among pigmentation phenotypes across the phylogeny. KEY RESULTS: In contrast to previous studies we found a bias towards transitions involving a gain in pigmentation, although transitions to phenotypes with both anthocyanin and yellow taxa are nevertheless extremely rare. Despite the dominance of yellow and anthocyanin-pigmented taxa, transitions between these phenotypes are constrained to move through a white intermediate stage, whereas transitions to double-pigmentation are very rare. The most abundant transitions are between anthocyanin-pigmented and unpigmented flowers, and similarly the most abundant polymorphic taxa were those with anthocyanin-pigmented and unpigmented flowers. CONCLUSIONS: Our findings show that pigment evolution is limited by the presence of other floral pigments. This interaction between anthocyanin and yellow pigments constrains the breadth of potential floral diversity observed in nature. In particular, they suggest that selection has repeatedly acted to promote the spread of single-pigmented phenotypes across the Antirrhineae phylogeny. Furthermore, the correlation between transition rates and polymorphism suggests that the forces causing and maintaining variance in the short term reflect evolutionary processes on longer time scales. PMID- 27192709 TI - Plant root tortuosity: an indicator of root path formation in soil with different composition and density. AB - BACKGROUND AND AIMS: Root soil penetration and path optimization are fundamental for root development in soil. We describe the influence of soil strength on root elongation rate and diameter, response to gravity, and root-structure tortuosity, estimated by average curvature of primary maize roots. METHODS: Soils with different densities (1.5, 1.6, 1.7 g cm-3), particle sizes (sandy loam; coarse sand mixed with sandy loam) and layering (monolayer, bilayer) were used. In total, five treatments were performed: Mix_low with mixed sand low density (three pots, 12 plants), Mix_medium - mixed sand medium density (three pots, 12 plants), Mix_high - mixed sand high density (three pots, ten plants), Loam_low sandy loam soil low density (four pots, 16 plants), and Bilayer with top layer of sandy loam and bottom layer mixed sand both of low density (four pots, 16 plants). We used non-invasive three-dimensional magnetic resonance imaging to quantify effects of these treatments. KEY RESULTS: Roots grew more slowly [root growth rate (mm h-1); decreased 50 %] with increased diameters [root diameter (mm); increased 15 %] in denser soils (1.7 vs. 1.5 g cm-3). Root response to gravity decreased 23 % with increased soil compaction, and tortuosity increased 10 % in mixed sand. Response to gravity increased 39 % and tortuosity decreased 3 % in sandy loam. After crossing a bilayered-soil interface, roots grew more slowly, similar to roots grown in soil with a bulk density of 1.64 g cm-3, whereas the actual experimental density was 1.48+/-0.02 g cm-3 Elongation rate and tortuosity were higher in Mix_low than in Loam_low. CONCLUSIONS: The present study increases our existing knowledge of the influence of physical soil properties on root growth and presents new assays for studying root growth dynamics in non-transparent media. We found that root tortuosity is indicative of root path selection, because it could result from both mechanical deflection and active root growth in response to touch stimulation and mechanical impedance. PMID- 27192710 TI - Minimal temperature of pollen germination controls species distribution along a temperature gradient. AB - BACKGROUND AND AIMS: Although plant distribution patterns are well documented, our understanding of the ecophysiological mechanisms that control the geographical ranges of plant species remains poor. We used a largely ignored method, the performance of the male gametophyte in vitro, to assess whether the thermal range of pollen germination and tube growth controls species distribution ranges, in this case along an elevational gradient. METHODS: Using in vitro pollen germination experiments, we obtained cardinal temperatures (minimal, optimal and maximal) of pollen germination and pollen tube growth for 25 herbaceous species along a mean annual temperature gradient of about 5 degrees C. These temperatures were correlated with temperatures of the sites where the species were collected. The presence of a phylogenetic signal in the data set as well as an effect of species flowering phenology were also estimated. KEY RESULTS AND CONCLUSIONS: We found a strong positive relationship between temperature conditions at our collection sites and the minimum temperature for both pollen germination and pollen tube growth. In addition, a significant correlation between maximum temperature of pollen tube growth and temperature of flowering month was apparent. We conclude that the restriction of pollen germination and growth by low temperatures is an important contributor to the climatic restriction of plant species distributions. Improved knowledge of this thermal precursor to seed production could, from a functional perspective, enhance our understanding of species distributions along climatic gradients and our ability to predict how anthropogenic climate change might affect plant community composition. PMID- 27192711 TI - Ethylene is involved in root phosphorus remobilization in rice (Oryza sativa) by regulating cell-wall pectin and enhancing phosphate translocation to shoots. AB - BACKGROUND AND AIMS: Plants are able to grow under phosphorus (P)-deficient conditions by coordinating Pi acquisition, translocation from roots to shoots and remobilization within the plant. Previous reports have demonstrated that cell wall pectin contributes greatly to rice cell-wall Pi re-utilization under P deficient conditions, but whether other factors such as ethylene also affect the pectin-remobilizing capacity remains unclear. METHODS: Two rice cultivars, 'Nipponbare' (Nip) and 'Kasalath' (Kas) were cultured in the +P (complete nutrient solution), -P (withdrawing P from the complete nutrient solution), +P+ACC (1-amino-cyclopropane-1-carboxylic acid, an ethylene precursor, adding 1 MUm ACC to the complete nutrient solution) and -P+ACC (adding 1 MUm ACC to -P nutrient solution) nutrient solutions for 7 d. KEY RESULTS: After 7 d -P treatment, there was clearly more soluble P in Nip root and shoot, accompanied by additional production of ethylene in Nip root compared with Kas. Under P deficient conditions, addition of ACC significantly increased the cell-wall pectin content and decreased cell-wall retained P, and thus more soluble P was released to the root and translocated to the shoot, which was mediated by the expression of the P deficiency- responsive gene OsPT2, which also strongly induced by ACC treatment under both P-sufficient and P-deficient conditions. CONCLUSIONS: Ethylene positively regulates pectin content and expression of OsPT2, which ultimately makes more P available by facilitating the solubilization of P fixed in the cell wall and its translocation to the shoot. PMID- 27192712 TI - Environmental and physiological effects on grouping of drought-tolerant and susceptible rice varieties related to rice (Oryza sativa) root hydraulics under drought. AB - BACKGROUND AND AIMS: Root hydraulic limitations (i.e. intra-plant restrictions to water movement) may be related to crop performance under drought, and groupings in the hydraulic function of drought-tolerant and drought-susceptible rice (Oryza sativa) varieties have been previously reported. This study aimed to better understand the environmental and physiological relationships with rice root hydraulics under drought. METHODS: Xylem sap bleeding rates in the field (gsap g 1shoot) were measured on seasonal and diurnal time frames, during which time environmental conditions were monitored and physiological measurements were conducted. Complementary experiments on the effects of vapour pressure deficit (VPD) on root hydraulic conductivity and on transpiration rates of de-rooted tillers were conducted in growth chambers. KEY RESULTS: The diurnal effects on bleeding rate were more closely related to irradiance than VPD, and VPD effects on root hydraulic conductivity measured on 21-day-old plants were due to effects on plant growth including root surface area, maximum root depth and root:shoot ratio. Leaf osmotic potential was related to the grouping of drought-tolerant and drought-susceptible varieties in rice root hydraulics, and these groupings were independent of differences in phenology. Low single-tiller bleeding rates were observed under high evapo-transpirational demand, higher bleeding rates were observed at more negative leaf osmotic potentials in drought-susceptible varieties, and drought-tolerant and susceptible varieties differed in the VPD induced increase in transpiration rates of de-rooted tillers. Low root suberin amounts in some of the drought-susceptible varieties may have resulted in higher ion transport, as evidenced by higher sap K+ concentration and higher bleeding rates in those varieties. CONCLUSIONS: These results provide evidence of the environmental effects on shoots that can influence root hydraulics. The consistent groupings of drought-tolerant and susceptible varieties suggest that traits affecting plant osmotic status may regulate root hydraulic response to drought in rice. PMID- 27192713 TI - Variable presence of the inverted repeat and plastome stability in Erodium. AB - BACKGROUND AND AIMS: Several unrelated lineages such as plastids, viruses and plasmids, have converged on quadripartite genomes of similar size with large and small single copy regions and a large inverted repeat (IR). Except for Erodium (Geraniaceae), saguaro cactus and some legumes, the plastomes of all photosynthetic angiosperms display this structure. The functional significance of the IR is not understood and Erodium provides a system to examine the role of the IR in the long-term stability of these genomes. We compared the degree of genomic rearrangement in plastomes of Erodium that differ in the presence and absence of the IR. METHODS: We sequenced 17 new Erodium plastomes. Using 454, Illumina, PacBio and Sanger sequences, 16 genomes were assembled and categorized along with one incomplete and two previously published Erodium plastomes. We conducted phylogenetic analyses among these species using a dataset of 19 protein-coding genes and determined if significantly higher evolutionary rates had caused the long branch seen previously in phylogenetic reconstructions within the genus. Bioinformatic comparisons were also performed to evaluate plastome evolution across the genus. KEY RESULTS: Erodium plastomes fell into four types (Type 1-4) that differ in their substitution rates, short dispersed repeat content and degree of genomic rearrangement, gene and intron content and GC content. Type 4 plastomes had significantly higher rates of synonymous substitutions (dS) for all genes and for 14 of the 19 genes non-synonymous substitutions (dN) were significantly accelerated. We evaluated the evidence for a single IR loss in Erodium and in doing so discovered that Type 4 plastomes contain a novel IR. CONCLUSIONS: The presence or absence of the IR does not affect plastome stability in Erodium. Rather, the overall repeat content shows a negative correlation with genome stability, a pattern in agreement with other angiosperm groups and recent findings on genome stability in bacterial endosymbionts. PMID- 27192714 TI - Emotional Intelligence: A Violence Strategy. PMID- 27192715 TI - A Survey on Main Semen Parameters in Natural Pregnancy and Intrauterine Insemination: Are There Any Significant Differences? AB - Intrauterine insemination (IUI) is a treatment of choice compared with other invasive and expensive techniques of assisted reproduction. Sperm quality is used to predict its outcome and success. Establishing threshold levels for sperm parameters is useful to avoid spending time and money to do other assisted reproductive techniques. This study was carried out to compare various semen parameters in a group of men eligible to participate in an IUI program with those of fertile men whose wives were pregnant at the time of the study. Two hundred and thirty-four semen samples were evaluated from subfertile men whose partners were candidates for IUI and 234 semen samples were evaluated from fertile men whose partners were pregnant less than 12 weeks. To assess the sensitivity and specificity of the main semen parameters, receiver operating characteristic (ROC) curves were used. Normal sperm morphology is more sensitive and specific compared with its progressive motility and concentration. No significant differences in various semen parameters of fertile men and those of the male partners of IUI candidates were observed. ROC analysis identified that sperm normal morphology using strict criteria may be a good indicator of fertility status in men. No significant difference in various semen parameters between the male partners of IUI candidates and the fertile men was seen. However, utilizing ROC curves, sperm morphology using strict criteria could be a good predictor of fertility. PMID- 27192716 TI - A Validation of the Group-Based Medical Mistrust Scale in Formerly Incarcerated Black and Latino Men. AB - While there is a growing body of literature on medical mistrust and its relevance to public health, research on formerly incarcerated Black and Latino men and their perception of mistrust toward medical providers and medical institutions remains scant. Very little is known about whether formerly incarcerated Black and Latino men mistrust medical and clinical providers given their previous experiences with the criminal justice system. It is important to determine whether medical mistrust play a key role in the health and health behaviors of released Black and Latino men. The purpose of this study is to validate and assess the psychometric properties of the Group-Based Medical Mistrust Scale for use among formerly incarcerated Black and Latino men in New York City. The findings of the exploratory and confirmatory factor analyses state that a two factor structure fit the data best. Two dimensions emerged as important subscales: discrimination and suspicion. The current findings suggest the two factor Group-Based Medical Mistrust Scale is a valid and reliable assessment tool to discern medical mistrust levels among formerly incarcerated Black and Latino men. PMID- 27192717 TI - A Descriptive Study Assessing Quality of Life for Adults With a Permanent Ostomy and the Influence of Preoperative Stoma Site Marking. AB - Diseases or anomalies of the genitourinary or gastrointestinal tract often require removal of organs and creation of an artificial opening (stoma) to allow for elimination of urine or stool. Preoperative stoma site marking can affect quality of life (QoL). A descriptive study was conducted to assess the relationship between QoL and preoperative stoma site marking in adults with a permanent ostomy. Using convenience sampling methods, 230 eligible participants attending a United Ostomy Association of America conference were invited to complete a survey of demographics regarding age, gender, time since surgeries, and ostomy type and the City of Hope National Medical Center Quality of Life Ostomy Questionnaire. The latter contains 2 sections of 30 and 43 items each that address life impact and quality of life, respectively. The researcher explained the study and provided a study packet to volunteers who were interested in participating. Volunteers were to complete the surveys over a 4-day period while at the conference; the investigator collected all study materials. Inclusion criteria stipulated study participants must be English writing/reading persons at least 18 years of age with a colostomy, ileostomy, or urostomy. All descriptive statistics (means, standard deviation, frequency, and percents) used to describe demographic and surgical history and quantitative data (logistic regression, cross-tabulation, Pearson product moment correlations, and analysis of covariance) used to determine relationships among factors were entered and analyzed using a computer software program. Of the 140 participants who met inclusion criteria and provided data, the majority (85, 60.7%) had their stoma site marked by a wound, ostomy, continence (WOC) nurse. WOC nurse marking was more likely in recent years, and WOC nurse marking was 1.03 times more likely for each year since stoma surgery (M = 13.44, SD = 13.48). Mean QoL was 7.56 (SD = 1.59, range 3.84-10.00) and was positively correlated with age (r [137] = 0.27, P = 0.001), years since first surgery (r (138) = 0.25, P = 0.003), and years since most recent surgery (r [137] =0.28, P = 0.001). The total number of surgeries was unrelated to QoL. More than 75% of the participants received preoperative marking, with a significant difference in QoL for persons marked by a surgeon (M = 7.71, SE = 0.16) or a WOC nurse (M = 8.82, SE = 0.37) versus another professional (M = 4.83, SE = 1.05) (F [3.118] = 3.44, P = 0.19). The increasing prevalence of preoperative stoma site marking by a WOC nurse over time serves as a benchmark for this centerpiece of WOC nursing practice. The findings confirm the need for stoma site marking and validate the impact of stoma site marking by the WOC nurse. PMID- 27192718 TI - A Retrospective, Observational Study of the Adequacy of Elective Loop Stoma Diversion. AB - Diverting stomas are employed for various clinical indications and easier to revert than end stomas. General, plastic, and colorectal surgeons continue to debate whether a diverting loop stoma adequately diverts stool, preventing spillage into the distal limb, which does not receive stool. A retrospective, descriptive study was conducted involving all patients who underwent loop ostomy surgery (colostomy or ileostomy) - defined by current procedural terminology (CPT) codes 44187, 44188, 44153, and 44155-44158 - between April 1, 2002 and October 12, 2010. The purpose of the study was to determine if a diverting loop stoma is completely diverting with no efflux into the distal limb by examining the rate of distal limb contamination. Two surgeons identified patients at the University of Virginia who had loop ostomy surgery and subsequently underwent computed tomography (CT) scan with oral contrast for clinical suspicion of abnormal pathology. A radiologist reviewed these images to evaluate the presence or absence of oral contrast in the ostomy distal limb. Distal progression of oral contrast was deemed adequate if oral contrast was visualized within the ostomy bag or if contrast was intraluminal distal to the loop ostomy. The loop ostomy was considered diverting if oral contrast was only visualized in the ostomy bag with no oral contrast distally. Of the 202 eligible patients, 26 (13%) underwent 41 postoperative CT scans of the abdomen/pelvis. Four (4) were excluded due to inadequate exam or confounding contrast (rectal contrast, contrast retention from preoperative scan). Of the remaining 22 patients with 35 CT scans (median age 54 [range 26-82] years, 10 men, 18 Caucasian, 18 having elective surgery), no patient (0%) had evidence of distal contrast. In this and other studies, loop stomas were found to provide adequate diversion without spillage into the nonfunctional limb for the vast majority of patients and should strongly be considered as the procedure of choice for temporary diversion. PMID- 27192719 TI - Hyperbaric Oxygen Therapy for the Adjunctive Treatment of Pyoderma Gangrenosum: A Case Report. AB - Pyoderma gangrenosum (PG) is a neutrophilic dermatosis of unknown etiology characterized by an ulcerative skin condition and confirmed through a diagnosis of exclusion. Management usually consists of systemic drug therapy, such as corticosteroids, sulfones, or immunosuppressants, either alone or in combination. Long-term use of these medications often has untold side effects. Hyperbaric oxygen therapy (HBOT) has been shown effective in the treatment of PG, reducing pain and tempering the need for medication. A case is presented of a 54-year-old woman with diabetes, hypertension, and a peptic ulcer who presented with painful, purulent ulcers on her buttocks, hands, and lower extremities of 2 weeks' duration. She was ultimately diagnosed with PG and provided 20 mg/day of oral prednisone for 1 week, tapered to 10 mg/day in the next week and then stopped. In addition, she received 12 sessions of HBOT - she breathed in 100% oxygen under 2.5 atmospheres absolute pressure for 90 minutes over 2 weeks. Her wounds healed without scarring. This excellent outcome including good wound healing, decreased pain, and reduced doses of systemic corticosteroids warrants additional study of the adjunctive use of HBOT for PG. PMID- 27192720 TI - Using the Literature to Understand Achilles' Fate. AB - According to Greek mythology, Achilles was fatally wounded in his heel, bled out, and died. Several unproven hypotheses mention poisoning, infection, allergy, hemophilia, thyrotoxic storm (ie, pain and stress), and suicide. The author, a plastic surgeon who often treats chronic wounds, proposes an additional scenario: Although not mortally wounded, Achilles was considered dead, because in his time a wounded hero was as good as a dead hero, so he lived out the remainder of his life as former hero with a chronic wound far away from everyone. To determine whether his injury was enough to cause fatal bleeding and quick death or if other factors might have been in play, a search of the literature was conducted to enhance what is known about Achilles, basically through the tale related in The Iliad and the clinical impact of an Achilles' injury. Search terms utilized included bleeding tibialis posterior artery (3 manuscripts were found) and chronic wound, Achilles tendon (631 manuscripts were located). Although science may not be able to explain how and why Achilles died, the literature supported the conjecture that Achilles probably had a chronic wound with skin and paratenon defect, de- vitalized tendon tissue, bleeding, granulation, and repeated infections. It is interesting to consider the state of his injury and his mind in the making of this legend. PMID- 27192721 TI - Case law update. Keys v. Alta Bates Summit Medical Center, N. A140038 (Ct. App. Cal. February 23, 2015). PMID- 27192723 TI - Case law update. Mackey v. Sarroca, No. 3-13-0219 (Ct. App. Ill. April 27, 2015). PMID- 27192722 TI - Case law update. Hammond v. Saini, 758 SE 2d 855 (N.C. 2014). PMID- 27192724 TI - Case law update. Whitlow v. Rideout Memorial Hospital, No. C074810 (Ct. App. 3rd Dist. Cal. June 9, 2015). PMID- 27192726 TI - Preface. PMID- 27192725 TI - Case law update. Baker v. Banner Health, Civil Action No. 12-cv-3029 (D. Colo. May 28, 2015). PMID- 27192727 TI - Standard Preparations, Limits of Potency, and Dating Period Limitations for Biological Products. Direct final rule. AB - The Food and Drug Administration (FDA or Agency or we) is amending the general biological products standards relating to dating periods and also removing certain standards relating to standard preparations and limits of potency. FDA is taking this action to update outdated requirements, and accommodate new and evolving technology and testing capabilities, without diminishing public health protections. This action is part of FDA's retrospective review of its regulations in response to an Executive order. FDA is issuing these amendments directly as a final rule because the Agency believes they are noncontroversial and FDA anticipates no significant adverse comments. PMID- 27192728 TI - Medicare and Medicaid Programs; Fire Safety Requirements for Certain Health Care Facilities. Final rule. AB - This final rule will amend the fire safety standards for Medicare and Medicaid participating hospitals, critical access hospitals (CAHs), long-term care facilities, intermediate care facilities for individuals with intellectual disabilities (ICF-IID), ambulatory surgery centers (ASCs), hospices which provide inpatient services, religious non-medical health care institutions (RNHCIs), and programs of all-inclusive care for the elderly (PACE) facilities. Further, this final rule will adopt the 2012 edition of the Life Safety Code (LSC) and eliminate references in our regulations to all earlier editions of the Life Safety Code. It will also adopt the 2012 edition of the Health Care Facilities Code, with some exceptions. PMID- 27192729 TI - Medicaid and Children's Health Insurance Program (CHIP) Programs; Medicaid Managed Care, CHIP Delivered in Managed Care, and Revisions Related to Third Party Liability. Final rule. AB - This final rule modernizes the Medicaid managed care regulations to reflect changes in the usage of managed care delivery systems. The final rule aligns, where feasible, many of the rules governing Medicaid managed care with those of other major sources of coverage, including coverage through Qualified Health Plans and Medicare Advantage plans; implements statutory provisions; strengthens actuarial soundness payment provisions to promote the accountability of Medicaid managed care program rates; and promotes the quality of care and strengthens efforts to reform delivery systems that serve Medicaid and CHIP beneficiaries. It also ensures appropriate beneficiary protections and enhances policies related to program integrity. This final rule also implements provisions of the Children's Health Insurance Program Reauthorization Act of 2009 (CHIPRA) and addresses third party liability for trauma codes. PMID- 27192730 TI - Deeming Tobacco Products To Be Subject to the Federal Food, Drug, and Cosmetic Act, as Amended by the Family Smoking Prevention and Tobacco Control Act; Restrictions on the Sale and Distribution of Tobacco Products and Required Warning Statements for Tobacco Products. Final rule. AB - The Food and Drug Administration (FDA) is issuing this final rule to deem products meeting the statutory definition of "tobacco product,'' except accessories of the newly deemed tobacco products, to be subject to the Federal Food, Drug, and Cosmetic Act (the FD&C Act), as amended by the Family Smoking Prevention and Tobacco Control Act (Tobacco Control Act). The Tobacco Control Act provides FDA authority to regulate cigarettes, cigarette tobacco, roll-your-own tobacco, smokeless tobacco, and any other tobacco products that the Agency by regulation deems to be subject to the law. With this final rule, FDA is extending the Agency's "tobacco product'' authorities in the FD&C Act to all other categories of products that meet the statutory definition of "tobacco product" in the FD&C Act, except accessories of such newly deemed tobacco products. This final rule also prohibits the sale of "covered tobacco products" to individuals under the age of 18 and requires the display of health warnings on cigarette tobacco, roll-your own tobacco, and covered tobacco product packages and in advertisements. FDA is taking this action to reduce the death and disease from tobacco products. In accordance with the Tobacco Control Act, we consider and intend the extension of our authorities over tobacco products and the various requirements and prohibitions established by this rule to be severable. PMID- 27192731 TI - Schedules of Controlled Substances: Placement of UR-144, XLR11, and AKB48 into Schedule I. Final rule. AB - With the issuance of this final rule, the Drug Enforcement Administration places (1-pentyl-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone (UR-144), [1-(5 fluoro-pentyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone (5-fluoro UR-144, XLR11), and N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide (APINACA, AKB48), including their salts, isomers, and salts of isomers whenever the existence of such salts, isomers, and salts of isomers is possible, into schedule I of the Controlled Substances Act. This scheduling action is pursuant to the Controlled Substances Act which requires that such actions be made on the record after opportunity for a hearing through formal rulemaking. This action imposes the regulatory controls and administrative, civil, and criminal sanctions applicable to schedule I controlled substances on persons who handle (manufacture, distribute, reverse distribute, import, export, engage in research, conduct instructional activities or chemical analysis, or possess), or propose to handle UR-144, XLR11, or AKB48. PMID- 27192732 TI - Schedules of Controlled Substances: Placement of Brivaracetam Into Schedule V. Interim final rule, with request for comments. AB - The Drug Enforcement Administration is placing the substance brivaracetam ((2S)-2 [(4R)-2-oxo-4-propylpyrrolidin-1-yl] butanamide) (also referred to as BRV; UCB 34714; Briviact) (including its salts) into schedule V of the Controlled Substances Act. This scheduling action is pursuant to the Controlled Substances Act, as revised by the Improving Regulatory Transparency for New Medical Therapies Act which was signed into law on November 25, 2015. PMID- 27192733 TI - Schedules of Controlled Substances: Temporary Placement of Butyryl Fentanyl and Beta-Hydroxythiofentanyl Into Schedule I. Final order. AB - The Administrator of the Drug Enforcement Administration is issuing this final order to temporarily schedule the synthetic opioids, N-(1-phenethylpiperidin-4 yl)-N-phenylbutyramide, also known as N-(1-phenethylpiperidin-4-yl)-N phenylbutanamide, (butyryl fentanyl) and N-[1-[2-hydroxy-2-(thiophen-2 yl)ethyl]piperidin-4-yl]-N-phenylpropionamide, also known as N-[1-[2-hydroxy-2-(2 thienyl)ethyl]-4-piperidinyl]-N-phenylpropanamide, (beta-hydroxythiofentanyl), and their isomers, esters, ethers, salts and salts of isomers, esters and ethers, into schedule I pursuant to the temporary scheduling provisions of the Controlled Substances Act. This action is based on a finding by the Administrator that the placement of butyryl fentanyl and beta-hydroxythiofentanyl into schedule I of the Controlled Substances Act is necessary to avoid an imminent hazard to the public safety. As a result of this order, the regulatory controls and administrative, civil, and criminal sanctions applicable to schedule I controlled substances will be imposed on persons who handle (manufacture, distribute, reverse distribute, import, export, engage in research, conduct instructional activities or chemical analysis, or possess), or propose to handle, butyryl fentanyl and beta hydroxythiofentanyl. PMID- 27192734 TI - Improve Tracking of Workplace Injuries and Illnesses. Final rule. AB - OSHA is issuing a final rule to revise its Recording and Reporting Occupational Injuries and Illnesses regulation. The final rule requires employers in certain industries to electronically submit to OSHA injury and illness data that employers are already required to keep under existing OSHA regulations. The frequency and content of these establishment-specific submissions is set out in the final rule and is dependent on the size and industry of the employer. OSHA intends to post the data from these submissions on a publicly accessible Web site. OSHA does not intend to post any information on the Web site that could be used to identify individual employees. The final rule also amends OSHA's recordkeeping regulation to update requirements on how employers inform employees to report work-related injuries and illnesses to their employer. The final rule requires employers to inform employees of their right to report work-related injuries and illnesses free from retaliation; clarifies the existing implicit requirement that an employer's procedure for reporting work-related injuries and illnesses must be reasonable and not deter or discourage employees from reporting; and incorporates the existing statutory prohibition on retaliating against employees for reporting work-related injuries or illnesses. The final rule also amends OSHA's existing recordkeeping regulation to clarify the rights of employees and their representatives to access the injury and illness records. PMID- 27192735 TI - Medicare Program; Obtaining Final Medicare Secondary Payer Conditional Payment Amounts via Web Portal. Final rule. AB - This final rule specifies the process and timeline for expanding CMS' existing Medicare Secondary Payer (MSP) Web portal to conform to section 201 of the Medicare IVIG and Strengthening Medicare and Repaying Taxpayers Act of 2012 (the SMART Act). The final rule specifies a timeline for developing a multifactor authentication solution to securely permit authorized users other than the beneficiary to access CMS' MSP conditional payment amounts and claims detail information via the MSP Web portal. It also requires that we add functionality to the existing MSP Web portal that permits users to: Notify us that the specified case is approaching settlement; obtain time and date stamped final conditional payment summary statements and amounts before reaching settlement; and ensure that relatedness disputes and any other discrepancies are addressed within 11 business days of receipt of dispute documentation. PMID- 27192736 TI - Regulations Under the Americans With Disabilities Act; Genetic Information Nondiscrimination Act. Final rule. AB - The Equal Employment Opportunity Commission (EEOC or Commission) is issuing its final rule to amend the regulations and interpretive guidance implementing Title I of the Americans with Disabilities Act (ADA) to provide guidance on the extent to which employers may use incentives to encourage employees to participate in wellness programs that ask them to respond to disability-related inquiries and/or undergo medical examinations. This rule applies to all wellness programs that include disability-related inquiries and/or medical examinations whether they are offered only to employees enrolled in an employer-sponsored group health plan, offered to all employees regardless of whether they are enrolled in such a plan, or offered as a benefit of employment by employers that do not sponsor a group health plan or group health insurance. Published elsewhere in this issue of the Federal Register, the EEOC also issued a final rule to amend the regulations implementing Title II of the Genetic Information Nondiscrimination Act (GINA) that addresses the extent to which employers may offer incentives for an employee's spouse to participate in a wellness program. PMID- 27192737 TI - [Musculoskeletal tumor. Update therapeutic strategies for bone sarcomas of spine and pelvis]. PMID- 27192738 TI - [I. Management of giant cell tumor of the spine and pelvis--current perspective]. PMID- 27192739 TI - [II. The evidence of local treatments for malignant bone tumors in pelvis and spine]. PMID- 27192740 TI - [III. An update on drug therapy for chordoma]. PMID- 27192741 TI - Genetic Information Nondiscrimination Act. Final rule. AB - The Equal Employment Opportunity Commission (EEOC or Commission) is issuing a final rule to amend the regulations implementing Title II of the Genetic Information Nondiscrimination Act of 2008 as they relate to employer-sponsored wellness programs. This rule addresses the extent to which an employer may offer an inducement to an employee for the employee's spouse to provide information about the spouse's manifestation of disease or disorder as part of a health risk assessment (HRA) administered in connection with an employer-sponsored wellness program. Several technical changes to the existing regulations are included. Published elsewhere in this issue of the Federal Register, the EEOC also issued a final rule to amend the regulations and interpretive guidance implementing Title I of the Americans with Disabilities Act (ADA) that addresses the extent to which employers may use incentives to encourage employees to participate in wellness programs that ask them to respond to disability-related inquiries and/or undergo medical examinations. PMID- 27192742 TI - Nondiscrimination in Health Programs and Activities. Final rule. AB - This final rule implements Section 1557 of the Affordable Care Act (ACA) (Section 1557). Section 1557 prohibits discrimination on the basis of race, color, national origin, sex, age, or disability in certain health programs and activities. The final rule clarifies and codifies existing nondiscrimination requirements and sets forth new standards to implement Section 1557, particularly with respect to the prohibition of discrimination on the basis of sex in health programs other than those provided by educational institutions and the prohibition of various forms of discrimination in health programs administered by the Department of Health and Human Services (HHS or the Department) and entities established under Title I of the ACA. In addition, the Secretary is authorized to prescribe the Department's governance, conduct, and performance of its business, including, here, how HHS will apply the standards of Section 1557 to HHS administered health programs and activities. PMID- 27192744 TI - Teaching the Real World: The UNC-NCSU BME Design Symposium. PMID- 27192743 TI - Is it Really Necessary to Keep My Pebble Smart Watch 2.5 cm from My Body? PMID- 27192745 TI - The Hygiene Hypothesis. PMID- 27192746 TI - Highlights in the History of the Fourier Transform. PMID- 27192747 TI - 30 Years and Still Going Strong. PMID- 27192749 TI - HOW Being a Home birth Midwife Enabled Me to Learn about SHOULDER DYSTOCIA. PMID- 27192748 TI - Cesarean Prevention Gains Some New Allies. PMID- 27192750 TI - The Fourth Stage: Sharing the Asian Way. PMID- 27192751 TI - First Hours after Birth: Family Integration and Mutual Regulation. PMID- 27192752 TI - Childbirth from a Bacteriological Perspective. PMID- 27192753 TI - Managing First Stage Problems. PMID- 27192754 TI - Opening the Pelvic Brim with Walcher's Position. PMID- 27192755 TI - A Vision of Birth. PMID- 27192756 TI - Waterbirth Basics: From Newborn Breathing to Hospital Protocols. PMID- 27192757 TI - Global Midwifery and the Humanization of Birth. PMID- 27192758 TI - The Endurinq Qualities in Midwifery. PMID- 27192759 TI - A Difficult Breech Birth. PMID- 27192760 TI - Midwifing Second Stage. PMID- 27192761 TI - The International MotherBaby Childbirth Initiative (IMBCI) A Human Rights Approach to Optimal Maternity Care. PMID- 27192762 TI - The Bond of Midwifery and Art. PMID- 27192763 TI - Margaret Stephen:The Ironies and Instruments of an 18th CenturvyLondon Midwife. PMID- 27192764 TI - Delayed Cord Clamping Requires a New Table for Stressed Newborns. PMID- 27192765 TI - A Slower Transition for Waterbirth Babies. PMID- 27192766 TI - Outside the Evidence: Births Missing from the Research. PMID- 27192767 TI - [Orbital radiographic anatomy. Part 2. Orbital soft tissue contents]. AB - OBJECTIVE: to study the characteristics of orbital soft tissues in health. MATERIAL AND METHODS: Computed tomography scans of 210 individuals (266 orbits) with no orbital abnormality were examined. RESULTS: The paper presents the volumetric characteristics and parameters of the soft tissue density of the orbit and its apex (extraocular muscles, retrobulbar fat, optic nerve, lacrimal gland, eye, and vitreous body) in health. The internal surgical space fat at the orbital apex is estimated to be 75.35 and 73.83% of the total volume at the apex in men and women, respectively. The paper shows that individual asymmetry of orbital fat volumes in health is encountered in 47.61% of the men and in 51.42% of the women and ranges from 0.5 to 2.0 cm3. CONCLUSION: The volumes of orbital soft tissues in health are statistically significant different in the men and in the women. The asymmetry of the mean orbital soft tissue volumes in health is within the limits of statistical error. PMID- 27192768 TI - [Variant radiation anatomy of the lacrimal sac at visualization by contrast-free computed tomography]. AB - OBJECTIVE: to morphometrically estimate normal variations in the sizes of lacrimal sacs on the basis of computed tomography findings to optimize the choice of endoscopic surgical intervention tactics for dacryocystitis. MATERIAL AND METHODS: Preoperative orbital computed tomography data were comparatively morphometrically processed in two groups of patients with or without clinically verified dacryo- cystitis. RESULTS: Data on the typical variants of the sizes of the lacrimal sac in health and in clinically manifested dacryocystitis were obtained and statistically processed. The advantages of using the design volume of the lacrimal sac over other measurements were shown. A method for the morphometry of lacrimal sacs was proposed on the strength of computed tomography data. CONCLUSION: The obtained new refined data on the holotopy of the lacrimal sac in health and clinically verified dacryocystitis can simplify the choice of an approach to planning endonasal dacryocystorhinostomy. PMID- 27192769 TI - [Use of phase-contrast magnetic resonance imaging to quantify cerebrospinal fluid dynamics in patients with communicating hydrocephalus]. AB - OBJECTIVE: to determine differences in cerebrospinal fluid (CSF) flow velocities in patients with varying degrees of communicating hydrocephalus (CH) versus a group of healthy volunteers without hydrodynamic disorders. MATERIAL AND METHODS: The investigation enrolled 27 CH patients (17 and 10 patients with an Evans index of 0.31 and 0.46, respectively) and 62 healthy volunteers. Average, volumetric, and peak flow velocities were determined at different intracranial levels. RESULTS: Analysis of differences between the mean values indicated that the patients with CH were observed to have progressive cranial cavity CSF outflow obstruction that depended on the degree of dilation of the ventricular system and, probably, on impaired CSF reabsorption. These changes can provide an explanation for the clinical symptoms present in the patients and also serve as diagnostic criteria. CONCLUSION: The investigation showed that phase-contrast magnetic resonance imaging might be used to estimate the quantitative indicators of CSF in health and in varying degrees of CH. The velocity characteristics of antegrade and retrograde CSF flows are significantly different in health and in disease, which may be relevant to neurologists and neurosurgeons when planning therapy and surgery options. PMID- 27192770 TI - Comparison of Radiological Assessments Patellar Resurfacing with Retention for Grade IV Osteoarthritis in Patellofemoral Joint accomplished Total Knee Arthroplasty. AB - INTRODUCTION: The purpose of this prospective study was to compare radiological outcomes after total knee artliroplasty (TKA) with or without patellar resurfacing in patients with grade IV osteoarthritis on patellofemoral joint. MATERIAL AND METHODS: 123 cases with Kellgren-Lawrence grade IV osteoarthritis on patellofemoral joint were enrolled for this study. At the operating room, they were randomly assigned to undergo patella resurfacing (62 cases) or patella retention (61 cases). Among them, 114 cases that could be followed for more than 2 years were included in this study (resurfacing group; 59 cases, retention group; 55 cases). Preoperative and postoperative radiological outcomes (mechanical femorotibial angle, patellar tilt and congruence angles) were evaluated and compared between two groups. RESULTS: Preoperative radiological measures shows not significant difference between patellar tilt (P = 0.13), mechanical femorotibial angles (P = 0.62) and congruence angle (P = 0.37). Despite the difference performed methods of surgery, postoperative radiological assessment outcomes between two groups were almost identical Patellar tilt (P = 0.47), mechanical femorotibial angles (P = 0.34) and congruence angle (P > 0.05). CONCLUSION: Obtained ahnost the same satisfactory radiological outcomes after patella resurfacing and retention groups after total knee replacement allows us to conclude that, primary TKA without patella resurfacing is a good treatment option in patients with high grade osteoarthritis of the patellofemoral joint. PMID- 27192771 TI - [Contrast-enhanced computed tomography is the required minimum in the diagnosis of abdominal and retroperitoneal space-occupying lesions]. AB - OBJECTIVE: to determine the advantages of contrast-enhanced computed tomography (CT) over contrast-free studies in the differential diagnosis of hepatic, renal, and pancreatic space-occupying lesions. MATERIAL AND METHODS. A team of experienced radiologists retrospectively used CT data of patients with different space-occupying lesions of the abdomen and retroperitoneal space (liver, kidney, and pancreas). RESULTS: The diagnostic value of CT of the liver, kidney, and pancreas substantially decreases without using radiopaque contrast agents; at the same time not only the differential diagnosis, but also visualization of some neoplasms are frequently impossible. CONCLUSION: The potential benefit of contrast-enhanced CT virtually always outweighs the risks associated with the injection of a contrast agent. PMID- 27192772 TI - [Comparative survey of radiation doses to patients in computed tomography in a federal hospital]. AB - OBJECTIVE: to analyze radiation exposure due to computed tomography (CT) of brain, chest, abdomen and pelvis in a large multi-field federal hospital and feasibility of low-dose CT-examinations. MATERIAL AND METHODS: Retrospective analysis was performed using data from electronic patient records and PACS from a single multi-field hospital. Data were obtained from 1626 records of patients (794 men, 832 women; age range 17-93) scanned with 3 MDCT during one year. CT examinations of good quality were selected, volumetric CT dose index (CTDI) and dose-length product (DLP) were collected for each of them. The effective doses (ED) were calculated using the normalized coefficients according to Russian Guidance. RESULTS. Number and structure of CT-examinations for the years 2012 2014 in a multi-field hospital were analyzed. The mean effective dose (M +/- m) values with/without contrast medium (respectively), according to anatomical areas were as follows: brain--2.34 +/- 0.03/3, 52 +/- 0.23, chest--4.83 +/- 0.11/11.02 +/- 0.82, abdomen-pelvis--9.81 +/- 0.40/36.6 +/- 1.17, chest-abdomen-pelvis - 12.41 +/- 0.79/35.63 +/- 1.81 mSv. CONCLUSION. Results of this study give an example of CT dose values and distribution in a multi-field hospital. They are compa- rable with reference levels published of other authors. This expe- rience should be expanded for creation of CT national reference values and for co operation with international initiatives (EUROSAFE projects). PMID- 27192773 TI - [Prostate biopsy under magnetic resonance imaging guidance]. AB - Prostate cancer (PC) is one of the most important problems in modern oncology. According to statistical data, PC ranks second in the cancer morbidity structure in the Russian Federation and developed countries and its prevalence has been progressively increasing over the past decade. A need for early diagnosis and maximally accurate morphological verification of the diagnosis in difficult clinical cases (inconvenient tumor location for standard transrectal biopsy; gland scarring changes concurrent with prostatitis and hemorrhage; threshold values of prostate-specific antigen with unclear changes in its doubling per unit time; suspicion of biochemical recurrence or clinical tumor progression after special treatment) leads to revised diagnostic algorithms and clinically introduced new high-tech invasive diagnostic methods. This paper gives the first analysis of literature data on Russian practice using one of the new methods to verify prostate cancer (transrectal prostate cancer under magnetic resonance imaging (MRI) guidance). The have sought the 1995-2015 data in the MEDLINE and Pubmed. PMID- 27192774 TI - CLINICAL ANALYSIS OF OSTEOARTICULAR NONTUBERCULOUS MYCOBACTERIAL INFECTION. AB - OBJECTIVE: The incidence rate of nontuberculous mycobacterial (NTM) infection has been increasing globally in recent years. However, reports of osteoarticular NTM infection are relatively rare. We report the characteristic clinical features of patients with osteoarticular NTM infection. PATIENTS AND METHODS: We examined 14 patients with osteoarticular NTM infection (mean age, 68 years) were treated in our hospital in the 20 years between 1995 and 2015. RESULTS: The rate of osteoarticular NTM infection in whole osteoarticular infection during the same period in our hospital was 2.7%. The NTM species. isolated from the 14 patients included Mycobacterium avium (n = 7), M. intracellulare (n = 5), M. fortuitum (n = 1), and M. kansasii (n = 1). Twelve patients had spinal involvements, and their levels were categorized as thoracic (n = 3), lumbar (n = 4), thoracolumbar (n = 1), and cervicothoracic (n = 4), with an average number of affected vertebra of 4.4. Nine patients had pulmonary lesions, including fibrocavitary (n = 5) and nodular/ bronchiectatic types (n = 4). Nine patients had lesions in sites other than the spinal and pulmonary regions, including the skin (n = 6), rib (n = 2), ilium (n = 2), humerus (n = 2), ulna (n = 1), wrist (n = 1), knee joint (n = 1), femur (n = 2), tibia (n = 1), toe (n = 1), and kidney (n = 1). In the initial examination, 11 patients were misdiagnosed, which delayed the final diagnosis in 7 patients. Six patients received chemotherapy with rifampicin, ethambutol, and clarithromycin, and 8 patients received other macrolide-based therapy. Five patients underwent surgical treatments in former hospitals, and 8 patients underwent surgical treatments (including salvage surgeries) in our hospital. With regard to outcome, 9 patients achieved healing, 2 patients with relapse were healed after retreatment, 1 patient was undergoing treatment, 1 patient had interrupted treatment, and 1 patient died during the treatment period. DISCUSSION: Osteoarticular NTM infection presented widely spread lesions in the spine and other various locations, mostly developed as a part of disseminated infection. Most patients were aged or immunosuppressed, but some patients were healthy individuals with no relevant medical history. Thus, if a patient is diagnosed with disseminated NTM infection, examination for possible lesions in other sites, including the bone and joint, should be performed. Cutaneous lesions, including subcutaneous abscess, were also characteristic. It is worth mentioning that such lesions can develop even under chemotherapy. Given the increasing trend in the overall incidence of NTM infection, awareness that NTM is a causative organism of osteoarticular infection is important. PMID- 27192775 TI - ASSOCIATION BETWEEN A pMAH135 PLASMID AND THE PROGRESSION OF PULMONARY DISEASE CAUSED BY MYCOBACTERIUM AVIUM. AB - BACKGROUND: Pulmonary disease caused by nontuberculous mycobacteria has a variable clinical course. Although this is possibly the result of not only host factors, but also bacterial factors, many questions remain to be answered regarding these manifestations. METHODS: To assess the relationship between the progression of pulmonary Mycobacterium avium disease and bacterial factors we performed variable number tandem repeats (VNTR) typing analysis of M. avium tandem repeats (MATR) in M. avium isolates from 46 patients with different clinical courses, and furthermore, examined the association between disease progression and a pMAH135 plasmid derived from M. avium. RESULTS: In patients whose treatment was initiated because of worsenedchest radiograph findings and/or clinical symptoms within 18 months after being diagnosed with pulmonary M. avium disease, the detection rate of 6 genes located in pMAH135 was 35.3-47.1% for 17 isolates. However, in untreated patients with a stable condition, these rates were 10.3-13.8% in 29 isolates. MATR-VNTR typing analysis showed that isolates from patients with worsened disease and those with stable disease are clustered differently. In cluster III, the number of isolates from patients with worsened disease was higher than that from patients with stable disease (p = 0.019), and furthermore, the number of isolates carrying pMAH135 genes was higher than that not carrying pMAH135 genes (p <= 0.001). CONCLUSION: These results indicate an association between the progression of pulmonary M. avium disease and pMAH135. The presence of pMAH135 genes might be a useful prognostic indicator for pulmonary M. avium disease and may serve as one criterion for treatment initiation. PMID- 27192776 TI - TUBERCULOSIS AND LUNG CANCER. AB - The occurrence of pulmonary tuberculosis (PTB) and lung cancer as comorbidities has been extensively discussed in many studies. In the past, it was well known that lung cancer is a specific epidemiological successor of PTB and that lung cancer often develops in scars caused by PTB. In recent years, the relevance of the two diseases has drawn attention in terms of the close epidemiological connection and chronic inflammation-associated carcinogenesis. In Japanese case series studies, most lung cancer patients with tuberculous sequelae received supportive care alone in the past, but more recently, the use of aggressive lung cancer treatment is increasing. Many studies on PTB and lung cancer as comorbidities have revealed that active PTB is noted in 2-5% of lung cancer cases, whereas lung cancer is noted in 1-2% of active PTB cases. In such instances of comorbidity, many active PTB cases showed Type II (non-extensively cavitary disease) and Spread 2-3 (intermediate-extensive diseases) on chest X rays, but standard anti-tuberculosis treatment easily eradicates negative conversion of sputum culture for M. tuberculosis; lung cancer cases were often stage III- IV and squamous cell carcinoma predominant, and the administration of aggressive treatment for lung cancer is increasing. The major clinical problems associated with PTB and lung cancer as comorbidities include delay in diagnosis (doctor's delay) and therapeutic limitations. The former involves two factors of radiographic interpretation: the principles of parsimony (Occam's razor) and visual search; the latter involves three factors of lung cancer treatment: infectivity of M.tuberculosis, anatomical limitation due to lung damage by tuberculosis, and drug-drug interactions between rifampicin and anti-cancer drugs, especially molecularly targeted drugs. The comorbidity of these two diseases is an important health-related issue in Japan. In the treatment of PTB, the possibility of concurrent lung cancer should be kept in mind, while in the treatment of lung cancer, the possibility of concurrent PTB should also be considered. PMID- 27192777 TI - COLLECTIVE VORTEX BEHAVIORS: DIVERSITY, PROXIMATE, AND ULTIMATE CAUSES OF CIRCULAR ANIMAL GROUP MOVEMENTS. AB - Ant mill, caterpillar circle, bat doughnut, amphibian vortex, duck swirl, and fish torus are different names for rotating circular animal formations, where individuals turn around a common center. These "collective vortex behaviors" occur at different group sizes from pairs to several million individuals and have been reported in a large number of organisms, from bacteria to vertebrates, including humans. However, to date, no comprehensive review and synthesis of the literature on vortex behaviors has been conducted. Here, we review the state of the art of the proximate and ultimate causes of vortex behaviors. The ubiquity of this behavioral phenomenon could suggest common causes or fundamental underlying principles across contexts. However, we find that a variety of proximate mechanisms give rise to vortex behaviors. We highlight the potential benefits of collective vortex behaviors to individuals involved in them. For example, in some species, vortices increase feeding efficiency and could give protection against predators. It has also been argued that vortices could improve collective decision-making and information transfer. We highlight gaps in our understanding of these ubiquitous behavioral phenomena and discuss future directions for research in vortex studies. PMID- 27192778 TI - INSURMOUNTABLE HEAT: THE EVOLUTION AND PERSISTENCE OF DEFENSIVE HYPERTHERMIA. AB - Fever, the rise in body temperature set point in response to infection or injury, is a highly conserved trait among vertebrates, and documented in many arthropods. Fever is known to reduce illness duration and mortality. These observations present an evolutionary puzzle: why has fever continued to be an effective response to fast-evolving pathogenic microbes across diverse phyla, and probably over countless millions of years? Framing fever as part of a more general thermal manipulation strategy that we term defensive hyperthermia, we hypothesize that the solution lies in the independent contributions to pathogen fitness played by virulence and infectivity. A host organism deploying defensive hyperthermia alters the ecological environment of an invading pathogen. To the extent that the pathogen evolves to be able to function effectively at elevated temperatures, it disadvantages itself at infecting the next (thermonormative) host, becoming more likely to be thwarted by that host's immune system and outcompeted by wild ecotype conspecifics (a genetically distinct strain adapted to specific environmental conditions) that, although more vulnerable to elevated temperatures, operate more effectively at the host's normal temperature. We evaluate this hypothesis in light of existing evidence concerning pathogen thermal specialization, and discuss theoretical and translational implications of this model. PMID- 27192779 TI - HOW MATE AVAILABILITY INFLUENCES FILIAL CANNIBALISM. AB - Parents sometimes eat their young to reduce the consequences of brood overcrowding, for nutritional gain, and/or to redirect investment toward future reproduction. It has been predicted that filial cannibalism should be more prevalent when mate availability is high as parents can more easily replace consumed young. Reviewing the available evidence--which comes almost exclusively from studies of paternal caring fish--we find support in some species, but not others. To explain this, we hypothesize that sexual selection against filial cannibalism and/or the tendency to acquire larger broods under conditions of high mate availability discourages filial cannibalism. Additionally, filial cannibalism might occur when mate availability is low to facilitate survival until access to mates improves. Since attractiveness can also influence remating opportunities, we review its effect on filial cannibalism, finding that attractive parents engage in less filial cannibalism. More research is needed to determine if this relationship is a result of individuals showing adaptive plasticity in filial cannibalism based on self-perceived attractiveness, or if the attractiveness of individuals is reduced by their propensity to commit filial cannibalism. More generally, to advance our understanding of how mate availability influences filial cannibalism, future studies should also focus on a wider range of taxa. PMID- 27192780 TI - The ODA as asking Oklahomans: Is Your Dentist an ODA Member? PMID- 27192781 TI - Oklahoma Dental Political Action Committee Update. PMID- 27192782 TI - ODA Hero of Dentistry Creed Cardon, Tulsa, OK. PMID- 27192783 TI - Building a Community of Dental Homes for Children. PMID- 27192784 TI - The Hygienist's Role In Comprehensive Case Presentation & Patient Education. PMID- 27192785 TI - Dental Sealant Pilot Program Serves At-Risk Students On-site. PMID- 27192787 TI - [Management of Common-law Marriage in Hospitalization for Medical Care and Protection Procedure after Abolishment of Guardianship System]. PMID- 27192788 TI - [Suicide Prevention and Mental Health Measures for Japanese University Students]. AB - According to the nationwide survey of the National University students in Japan, the annual suicide rate in 2012 was 15.7 per 100,000 undergraduate students. In many universities, suicide prevention is an important issue regarding mental health measures, and each university is actively examining this. The current situation concerning measures for suicide prevention in the Japanese National Universities was investigated in 2009. In 2010, the "college student's suicide prevention measures guideline, 2010" was established based on the results of this investigation. This guideline refers to the basic philosophy of suicide prevention in Chapter 1, risk factors for suicide in Chapter 2, and systems and activities for suicide prevention in Chapter 3. The Health Service Center, Okayama University plays central roles in mental health and suicide prevention measures on the Medical Campus. The primary prevention includes a mini-lecture on mental health, classes on mental health, and periodic workshops and lectures for freshmen. The secondary prevention includes interviews with students with mental health disorders by a psychiatrist during periodic health check-ups and introducing them to a hospital outside the university. The tertiary prevention includes support for students taking a leave of absence to return to school, periodic consultation with such students with mental disorders, and postvention following a suicide. We believe that for mental health measures on the university campus, it is important to efficiently make use of limited resources, and that these efforts will eventually lead to suicide prevention. PMID- 27192786 TI - [Identification of Psychotropic Drugs Attributed to Fatal Overdose--A Case control Study by Data from the Tokyo Medical Examiner's Office and Prescriptions]. AB - Drug overdose is a serious public health issue and fatal cases have been reported from various fields of medicine. This case-control analysis assessed the comparison between fatal overdose cases in the special wards of Tokyo Metropolitan area and prescribed psychotropic drugs in Tokyo in 2009-2010. It was suggested that the prescribed drugs serve as a direct cause of death in overdose cases. Furthermore, pentobarbital calcium, chlorpromazine-promethazine phenobarbital, levomepromazine and flunitrazepam were identified as drugs with a high risk of fatal overdose. It is encouraged to prudently verify the intended application and usage of such psychotropic drugs in each case upon their prescription. This is the first study in Japan to identify psychotropic drugs with a high risk of fatal overdose by case-control study. PMID- 27192789 TI - [Designing and Operating a Comprehensive Mental Health Management System to Support Faculty at a University That Contains a Medical School and University Hospital]. AB - In Japan, healthcare professionals and healthcare workers typically practice a culture of self-assessment when it comes to managing their own health. Even where this background leads to instances of mental health disorders or other serious problems within a given organization, such cases are customarily addressed by the psychiatrists or psychiatric departments of the facilities affected. Organized occupational mental health initiatives for professionals and workers within the healthcare system are extremely rare across Japan, and there is little recognition of the need for such initiatives even among those most directly affected. The author has some experience designing and operating a comprehensive health management system to support students and faculty at a university in the Tokyo Metropolitan Area that contains a medical school and university hospital. At this university, various mental health-related problems were routinely being allowed to develop into serious cases, while the fundamental reforms required by the health management center and the mental health management scheme organized through the center had come to represent a challenge for the entire university. From this initial situation, we undertook several successive initiatives, including raising the number of staff in the health management center and its affiliated organizations, revising and drafting new health management rules and regulations, launching an employment support and management system, implementing screenings to identify people with mental ill-health, revamping and expanding a counselling response system, instituting regular collaboration meetings with academic affairs staff, and launching educational and awareness-raising activities. This resulted in the possibility of intervention in all cases of mental health crisis, such as suicidal ideation. We counted more than 2,400 consultations (cumulative total number; more than half of consultations was from the medical school, postgraduate medical course, or hospitals) on a campus comprising 8,700 people, in which our problem-solving approach was able to achieve a certain degree of success in a majority of cases. Amid the increasing prevalence of mental ill-health and signs of worsening mental health problems in all areas of society, I look forward to the establishment of occupational mental health systems that are suited to medical institutions. PMID- 27192790 TI - [Mental Health and Prevention of Suicide in Japanese Workplaces Based on a Pilot Study of Job Stress and Suicide Ideation]. AB - The Japanese suicide rate is still high compared with other countries. Worker suicide especially leads to marked social and economic losses and severely affects the bereaved. There is an urgent need to devise a system to prevent suicide at a very early stage. Generally, it is considered very difficult to intervene and prevent suicide in cases in which individuals kill themselves suddenly. However, according to some studies on suicide attempts, even those who killed themselves suddenly had experienced some kind of conflict or a desire to die for a long period. Therefore, it is essential to analyze the risk factors at an early stage when individuals have vague thoughts of suicide. This will help reduce the risk of suicide in such cases. In this article, I first survey the data related to workers' mental health in Japan. Second, I introduce the results of our pilot study in which we investigated mental health issues related to suicide among workers who have taken leave from work for more than two months. In this study, workers who do not exhibit help-seeking behavior are suggested to be a high-risk group for suicide. It is speculated that this behavior is related to several factors such as the sex, age, social status, education, personal stigma, and perceived stigma. Therefore, we must focus on both clinical and social solutions for the prevention of suicide. I believe that psychiatrists will come to play a more important role as liaisons between workplaces and social resources for the prevention of suicide. PMID- 27192791 TI - [National Guidelines and Useful Guidance for Psychiatrists When Cooperating with Companies]. AB - Good coordination between the principal doctor and companies will benefit workers with mental health disorders, and for that reason a common understanding is required. Companies seeks to preserve a workers' health from the viewpoint of obligation of security, while "caseness", being the trouble in the companies, is undesirable from the viewpoint of risk management. The principal doctor needs to understand that the companies reaction sets the caseness above the illness. There are various national guidelines and forms of guidance for workers' mental health."Guidelines for the Promotion of Workers' Mental Health at Work"was indicated in 2000 for the development of an organizational framework, and the "Manual on Workplace Reentry Support for Workers Returning from Leave Due to Mental Health Issues" was indicated in 2004. "Certification Criteria for Mental Disorders Caused by Psychological Stress" was also indicated in 2011 and, in which, harassment was recognized as an injury of workers. In many cases, companies consider employees with mental health disorders with these guidelines and guidance in mind to avoid lawsuits, and principal doctors are similarly expected to share a common understanding, promoting favorable coordination. PMID- 27192792 TI - [The Utility of XE-2 100 Analyzer's NEUT-X and NEUT-Y Parameters for Detecting Neutrophil Dysplasia in Myelodysplastic Syndromes]. AB - Morphological abnormalities of blood cells are the typical characteristics of myelodysplastic syndromes (MDS). Recently, the usefulness of multiparameter automatic hematology analyzer XE-2100 for detecting neutrophil dysplasia has been reported by using parameters of NEUT-X and NEUT-Y, reflecting neutrophil cytoplasmic granularity and the cellular content of nucleic acid and protein, respectively. We evaluated the utility of these parameters by analyzing the blood samples of fifty MDS patients consulting Kakogawa West Municipal Hospital between Jan, 2010 and Jun, 2014, as well as 100 persons undergoing medical examinations during the same period as controls. Neutrophil granulation level was classified as normal, hypo-granular, or agranular under microscopic observation, and degranulation index was calculated using the following formula. The relationship between NEUT-X, NEUT-Y values and degranulation index was studied as below. Degranulation index = agranular (%) x 2+ hypo-granular (%) x 1 + normal (%) x 0 Neut-X values of MDS patients were 1,350 (mean), 1,345 (median), and NEUT-Y values, 430 (mean) and 432 (median). The NEUT-X and NEUT-Y values of control patients were 1,350, 1,349, 446 and 445, respectively. Correlation efficiency between degranulation index and NEUT-X or NEUT-Y were r = 0.62 or 0.52, respectively. Relationship between NEUT-X and NEUT-Y for all patients was r = 0.90. All the 10 patients showing NEUT-X lower than 1,315 and NEUT-Y lower than 400 simultaneously were MDS. Hence, we conclude that NEUT-X and NEUT-Y information is useful for quantitative evaluation of neutrophil morphological abnormalities. PMID- 27192793 TI - [Study of Somatosensory Event-Related Potential in Mood Disorder]. AB - There have been a number of inconsistent previous reports indicating that mood disorder patients are relatively sensitive or conversely insensitive to physical pain. However, there have been few such studies examining pain using neurophysiological techniques. The present study was performed to investigate the differences in tactile sense recognition between mood disorder patients and control subjects using a tactile sense recognition P300 measuring system. Tactile stimuli were delivered to the index finger as frequent stimuli and to the ring finger as infrequent stimuli. Subjects were requested to press a button promptly and accurately in response to infrequent stimuli. N140 and P300 were measured in the event-related potential to infrequent stimulus paradigm. The subjects evaluated stimuli on a visual analog scale (VAS). The amplitudes of P300 were smaller for the mood disorder patients than for control subjects. The VAS scores of mood disorder patients were significantly higher than those of control subjects. In mood disorder patients, the amplitude of P300 was negatively correlated with the HAM-D score. These results suggest dysfunction of tactile sense recognition in mood disorder patients. In addition, the amplitude of P300 may be useful as a biological marker for psychological conditions in mood disorder patients. PMID- 27192794 TI - [Multivariate Analyses on Clinical Utility and Sources of Variation of Serum Presepsin as a Diagnostic Marker for Sepsis]. AB - OBJECTIVE: Clinical utility of a new marker for sepsis, presepsin, was evaluated by use of a case-control study design. METHOD: Enrolled in the study were seventy one consecutive cases for whom blood culture was ordered in suspicion of sepsis. After the culture, 36 subjects were diagnosed as having a state of sepsis (S group) and 35 were denied of sepsis (NS group). The serum level of presepsin was measured together with basic chemistry tests and complete blood counts at the time of diagnosis. RESULTS: Median serum presepsin for the two groups were 1,602 and 586 pg/mL, respectively. The difference was significant by Mann-Whitney test (P < 0.001). Logistic regression analysis was performed to evaluate contribution of presepsin in diagnosing sepsis in comparison with other markers for septic state. The result showed that presepsin was most powerful in predicting sepsis together with monocyte count percent (Mo). The diagnostic accuracy by use of logistic equation including both presepsin and Mo was 0.86 in terms of area under ROC curve (AUC), whereas AUC by use of an equation with presepsin alone was 0.80. Additionally, multiple regression analysis was performed to evaluate sources of variation of presepsin. It revealed that serum albumin and eGFR were negatively associated with serum level of presepsin. CONCLUSION: It is recommended to look at Mo together with presepsin in the diagnosis of sepsis. Serum level of presepsin is raised in the presence of renal dysfunction and/or hypoalbuminemia. PMID- 27192796 TI - [The Role of Anti-Oxidative Stress in HDL]. AB - High-density lipoprotein(HDL) particles play a role in anti-oxidative stress, and this action is partially involved in the anti-atherosclerotic processes. Indeed, a decreased level of anti-oxidative stress in HDL has been reported in oxidative stress-related pathologies. As typical HDL-containing protein molecules, apolipoprotein A-I (apoA-I), paraoxonase-1 (PON1), and lipoprotein-associated phospholipase A2 (Lp-PLA2) are mainly described in the present review. Numerous studies have demonstrated that a low apoA-I level and the oxidative modification of apoA-I is associated with a dysfunction of anti-oxidative stress in HDL. A low PON1 level also plays a significant role in the dysfunction of anti-oxidative stress in HDL. Several studies have shown Lp-PLA2 to have an anti-atherosclerotic ability, while there have also been clinical studies showing a positive association between the Lp-PLA2 level and atherosclerotic manifestations. There are other HDL-containing protein molecules related to the anti-oxidative stress system in HDL, and all of these should be further investigated. The treatment of oxidative stress-related pathologies can lead to an improvement or even a full recovery of the anti-oxidative stress function in HDL. Given the multiple functions of HDL particles and the limitations associated with only HDL cholesterol measurements, a comprehensive assessment of HDL particles, which includes the role of anti-oxidative stress in HDL, is thus considered to be necessary in future practice. PMID- 27192795 TI - [Introduction]. AB - It is well-known that plasma HDL-C shows a negative correlation with the incidence of coronary artery disease, which was confirmed by the Framingham Study, a famous prospective cohort study, in 1977. At first, HDL-C was determined by the precipitation method, and then the homogeneous method of HDL-C determination was developed in the 1990's in Japan. This method enabled HDL-C measurement in a short time for many samples. HDL removes free cholesterol from somatic cells by accepting cell cholesterol via ATP-binding cassette transporter A1. Cholesterol ester in HDL is transferred to VLDL and LDL by the action of cholesterol ester transfer protein or is incorporated into the liver via SR-BI. This pathway is called reverse cholesterol transport, which can regress atheromatous plaques. On the other hand, some CETP inhibitors, which can increase the HDL-C level have been developed in the world. However, the development of all candidate drugs was stopped because of side or insufficient effects. In addition, patients with CETP deficiency, whose HDL-C levels are markedly high, sometimes show the findings of coronary artery disease. These observations indicate that elevating HDL-C levels alone may not lower the cardiovascular disease risk. Recently, it was reported that HDL has pleiotropic functions other than reverse cholesterol transport. Actually, HDL inhibits lipid oxidation, impairs leukocyte adhesion and monocyte activation, promotes nitric oxide production, and inhibits the activation of platelets and the coagulation cascade. Functional characterization of HDL is, therefore, necessary for precise assessment of the cardiovascular risk and effectiveness of risk reduction. PMID- 27192797 TI - [Molecular Mechanism and Evaluation Method for Anti-Inflammatory HDL]. AB - Plasma concentrations of high-density lipoprotein cholesterol (HDL-C) are inversely correlated with the risk of coronary artery disease (CAD). The cardioprotective effect of HDL is attributable to its reverse cholesterol transport capacity from peripheral cells to the liver. HDL has a variety of anti inflammatory, anti-oxidative, and anti-apoptotic properties. However, recent interventional therapies using CETP inhibitors or niacin did not prove to be of benefit in the reduction of cardiovascular risks. This discrepancy is often explained by the quality of HDL particles. HDL particles undergo oxidation, chloralization, nitration, and calbamilation, under conditions due to inflammatory or metabolic disorders. HDL particles with these modifications may lose their atheroprotective effects and promote inflammatory processes, being referred to as dysfunctional HDL. HDL consists of a variety of phospholipids and proteins such as apolipoprotein A-I and paraoxonase-1. Because these components in the HDL particle regulate anti-atherosclerotic effects, the significance of HDL should be evaluated based on the HDL function. Reliable assays and surrogate markers of HDL function will be useful for evaluating the efficacy of HDL targeted interventions against atherosclerosis. In this review, we summarized the mechanism of anti-inflammatory effects on HDL and assays for evaluating HDL functions. PMID- 27192798 TI - [Role of HDL in Cholesterol Efflux and Reverse Cholesterol Transport]. AB - Low plasma levels of HDL-cholesterol (HDL-C) have been consistently associated with an increased risk of atherosclerotic cardiovascular diseases (CVD), and it is thus considered to be an anti-atherogenic lipoprotein. The development of novel therapies to enhance the atheroprotective properties of HDL may have the potential to further reduce the residual risk. Reverse cholesterol transport (RCT) is believed to be a primary atheroprotective property of HDL and its major protein, apolipoprotein A-I(apoA-I). HDL and apoA-I have been shown to promote the efflux of excess cholesterol from macrophage-derived foam cells via the cholesterol transporters, ATP-binding cassette transporter A1 (ABCA1), ABCG1, and scavenger receptor class B, type I (SR-BI), and then transport it back to the liver for excretion into bile and eventually into the feces. In this regard, a validated murine assay that quantifies macrophage RCT may be a better predictor of atherosclerosis than the steady-state plasma concentration of HDL-C. Indeed, a recent clinical study demonstrated that the ability of serum HDL to mediate cholesterol efflux from macrophages was independently and negatively associated with the CVD risk even after adjustment for HDL-C levels, suggesting that HDL functionality is more important than its quantity. Therefore, the future development of HDL-targeted therapy should take both aspects into consideration to further reduce the residual risk. PMID- 27192799 TI - [Anti-Thrombotic Properties of High-Density Lipoprotein]. AB - Along with the established evidence on the association between a low HDL cholesterol level and arterial thrombosis, several limited studies have suggested that low HDL cholesterol is also a risk factor for venous thrombosis, such as deep vein thrombosis and pulmonary embolism. As well as emerging evidence from clinical studies, basic research has proposed the interaction between HDL and key molecules in the field of thrombosis and hemostasis; HDL interacts with megakaryocytes to affect the production of platelets, suppresses the aggregation of platelets, protects against the injury of endothelial cells, and inhibits coagulation and fibrinolysis cascades. Considering these reports together, HDL can possess anti-thrombotic properties as one of its pleiotropic effects other than its role in the reverse transport system of cholesterol. Further study on the basic mechanism of this property of HDL and medical applications are expected to lead to the development of novel anti-thrombotic reagents and new laboratory tests for thrombosis and hemostasis in the future. PMID- 27192800 TI - [Sex Specificity in Age-Related Thyroid Hormone Responsiveness]. AB - Similar to other systems, the endocrine system is affected by aging. Thyroid hormone, the action of which is affected by many factors, has been shown to be associated with longevity. The most useful marker for assessment of the thyroid hormone action is the TSH level. Although age and sex are believed to modify the pituitary set point or response to the free thyroid hormone concentration, the precise age- and sex-dependent responses to thyroid hormone have yet to be reported. In this lecture, molecular aspects of resistance to thyroid hormone are initially overviewed. After presentation of the evidence that the TSH-thyroid hormone axis is evolutionarily modified, and that negative feedback mechanisms may start to play roles in homeostatic regulation at the time of delivery, the rationale of age-dependent thyroid hormone resistance is introduced. To assess the age- and sex-dependent resistance to thyroid hormone, the index is provided by the formula based on the relationship between thyroid hormone and TSH levels. The index is calculated by the results of thyroid function tests obtained from the two individual clinical groups. From the results, there were negative relationships between the free T3 resistance index and age in males of both groups, while there were no apparent relationships in females. These findings indicate that there is a male-specific response to thyroid hormone with aging. Furthermore, the specific features of the response may not be affected by environmental factors such as the presence of disorders or medical treatments. PMID- 27192801 TI - [Human Resource Development for Tohoku Region after Great East Japan Earthquake: Remarks of the Chairperson]. AB - In order to promote further advances of medical systems in the Tohoku region where the Great East Japan Earthquake and the subsequent accident at the Fukushima Dai-ichi Nuclear Power Plant occurred, the requirement of human resources in clinical laboratory medicine has increased. Therefore, the symposium entitled "Human resource development for Tohoku region after Great East Japan Earthquake" was held in The 47th Tohoku Regional Congress of Japanese Society of Laboratory Medicine. In Fukushima Prefecture, the Thyroid Ultrasound Examination program has been conducted since Oct. 2011. Educational courses and certification programs for thyroid ultrasound examiners were established for medical doctors and technologists in Fukushima. The need for certified sonographers has also increased because deep venous thrombosis is also one of the health problems in the earthquake-hit area. Human resource development of sonographers was discussed in this symposium. In addition, further advances in clinical laboratory medicine are dependent on the development of specified medical technologists and certified physicians. Projects of human resource development currently performed in the Tohoku region were introduced and future actions were discussed. PMID- 27192802 TI - [Human Resource Development for Thyroid Ultrasound Examination Program in Fukushima]. AB - As a response to the health effects associated with the Fukushima Daiichi Nuclear Power Plant accident that occurred after the Great East Japan Earthquake, the Thyroid Ultrasound Examination program as a part of the Fukushima Health Management Survey was started on Oct. 9th, 2011. Since this project required a large-scale cohort comprising all residents aged <= 18 years living in Fukushima when the earthquake happened, the nurturing of many ultrasound examiners was a matter of great urgency. Moreover, the standardization of examination procedures and skills of examiners were also important issues. Therefore, educational projects were established to develop ultrasound skills for medical doctors and technicians in Fukushima Prefecture. Marked efforts for this project resulted in increases in ultrasound examiners and institutions taking part in the Thyroid Ultrasound Examination project. Medical technicians specialized in ultrasound examinations are actively involved in these educational projects. We report the details of human resource development projects from the point of view of such medical technicians. PMID- 27192803 TI - [Viewpoint: Skill Certifications for Japanese Medical Technologists]. AB - With the development of medicine, the field of clinical laboratory medicine evolves rapidly, and it will be more specialized in the near future. Medical technologists are required to hone their skills and knowledge, in order to keep up with the evolution. In recent years, board certifications by several medical societies are considered to indicate the skills of medical technologists. The number of board-certified medical technologists in populated areas such as Tokyo, Kanagawa, Osaka, and Fukuoka is greater than in less populated areas such as Kyusyu and Tohoku. The rate of certified medical technologists among prefectures is the highest in Mie (10.1%), followed by Nagasaki (8.8%). Tokyo, Ishikawa, Kyoto, and Osaka have acquisition rates greater than 7%. In contrast, prefectures of Miyazaki, Kumamoto, Yamanashi, and Akita have low acquisition rates of less than 4%. Being certified is not only an opportunity for personal career advancement, but also a chance to improve the laboratory. More technologists are being certified in our laboratory, and we are encouraging a future increase in their number. However, there are some problems to be overcome. Assignment of competent staff and long-term and premeditated rotation are considered to be important for staff to find the work rewarding, and the laboratory to be trusted by physicians. PMID- 27192804 TI - [Industry-Academia Collaboration in the Clinical Laboratory Field: Chairmen's Introductory Remarks]. AB - Industry-academia collaboration has become essential in contemporary medicine. Therefore, many institutes including university corporations have promoted the establishment of an endowed chair and/or performed collaborative research. This symposium was held to overview the present status of industry-academia collaboration in the clinical laboratory field. As a representative of the industry, Mr. Taniguchi (Sysmex) presented the development process of M2BP Glycosylation Isomer, a new marker for liver fibrosis. Mr. Saitoh (Horiba) introduced the achievements of joint collaborative research with Kyoto Prefectural University of Medicine, especially the practical realization of an automated hematology analyzer capable of simultaneously measuring C-reactive protein. Mr. Setoyama (LSI Medience) presented on the characteristic collaboration between academia and commercial laboratories such as Tsukuba Medical Laboratory of Education and Research (TMER). On the other hand, as a representative of academia, Associate Prof. Imai (Kyoto Prefectural University of Medicine) summarized the necessity of clinical laboratories spread regenerative medicine. Finally, Prof. Koshiba (Hyogo College of Medicine) presented on the industry-academia collaboration in routine laboratory work in his institute. PMID- 27192807 TI - Healthcare and self-care dovetail as themes at business conference. PMID- 27192805 TI - [Experience of Collaborative Research through Department of Medical Instrumental Research and Technology in Kyoto Prefectural University of Medicine]. AB - Both of Kyoto Prefectural University of Medicine which offers high, technical and safe medical treatment and Horiba, Ltd. which has small CBC analyzers in a core product established a joint research institute for development of advanced laboratory test analyzer from January 1, 2012 in Kyoto Prefectural University of Medicine as the "advanced treatment hospital" where the Ministry of Health, Labour and Welfare has got approved. Clinical needs about analyzer and reagent for a laboratory test are being investigated to the emergency medical care unit and the intensive care unit as well as the laboratory test part in the affiliated hospital and many medical departments of the pediatrics, the internal medicine and the surgery. Developing the new analyzer based on high technology, evaluating the performance of them and spreading them to a medical examination and treatment site is our main target. PMID- 27192808 TI - OR Manager Conference keynote makes compelling case for compassion in patient care. PMID- 27192809 TI - ERAS improves outcomes, shortens length of stay. PMID- 27192810 TI - Committee saves over $1 million through cost conscious initiatives. PMID- 27192811 TI - Post-OR career path may lead to business opportunity--Part 2. PMID- 27192812 TI - Two hospitals face value-based payment--which one does your OR resemble? PMID- 27192813 TI - Ophthalmic ASCs have eyes on the prize as the specialty expands. PMID- 27192814 TI - [ADULT STEM CELLS AND CELLS OF MALIGNANT ORIGIN. PART II]. AB - Recent data on adult stem cells are reviewed. According to the present dominant paradigm, it is most probable that cancer predisposition arises or cancer is initiated in these cells. PMID- 27192815 TI - [ASSOCIATION BETWEEN FOUR SEROTONIC GENES POLYMORPHISM (5HTTL, 5HT1A, 5HT2A, AND MAOA) AND PERSONALITY TRAITS IN WRESTLERS AND CONTROL GROUP]. AB - This study presents the data on the polymorphisms of the serotonin system genes (5-HTTL, 5-HT1A, 5-HT2A, and MAOA) in male and female wrestlers and in the control group. The population genetics analysis of the 5HTTL gene showed the highest frequency of the SS genotype 5-HTTLPR in sportsmen (p = 0.04), as well as the trend toward higher frequency of united genotypes of the locus of 5-HTTLPR VNTR and SNP rs25531--SASA (p = 0.06) in comparison with the control group. As for the polymorphisms for other genes 5-HT1A (rs6295), 5-HT2A (rs6311), and MAOA (VNTR), we found no significant differences between the groups tested. Using the NEO PI-R questionnaire we analyzed the possible correlations between the genotypes and the psychological traits in our samples. It was demonstrated that the athletic success in elite sportsmen was associated with lower openness to experience and higher conscientiousness. The interaction effect of the gender and 5-HT2A on the self-rating for openness to experience, interaction effect of the level of the sport success and 5-HT2A, and the interaction effect of the gender and 5-HT1A genotype on self-reported conscientiousness were observed as a trend. PMID- 27192816 TI - [CITRULLINUREIDASE GENE DIVERSITY IN THE GENUS FRANCISELLA]. AB - This work describes the results, of the in silico analysis of the genetic diversity of the citrullinureidase gene (ctu) in two species of bacteria of the genus Francisella: tularensis (ssp. tularensis, holarctica, mediasiatica, novicida) and philomiragia. The strains of the Central Asiatic subspecies possessing the citrullinureidase activity differ in the gene ctu from the ssp tularensis Schu by three nucleotide substitutions leading to two insignificant amino acid substitutions in the encoded polypeptide. In the strain F. tularensis of the ssp. holarctica the gene ctu encodes inactive enzyme, which is probably due to amino acid substitutions: 151 Gly --> Asp, 183 Pro --> Leu, 222 Asp --> Asn. Except for the Japan biovar bacteria, in all strains of the Holarctic subspecies there are two stop codons in the gene ctu. The bacteria of the subspecies novicida contain the ctu gene only in the strain 3523, whereas the other strains contain the gene FTN_0827 encoding the C-N hydrolase, which probably provides the citrullinureidase activity. PMID- 27192817 TI - [A METHOD FOR DIFFERENTIATION OF BACILLUS ANTHRACIS STRAINS AND PHYLOGENETICALLY RELATED SPECIES BASED ON DETERMINATION OF THE STRUCTURAL DIFFERENCESBETWEEN CHROMOSOMAL GENES FOR BIOSYNTHESIS OF FLAGELLIN AND METHIONINE]. AB - Nucleotide sequence analysis of several genes responsible for the anthrax pathogen definitive properties--motility and penicillinase activity--determined a chromosomal locus promising for interspecies differentiation. We demonstrated that the gene fliC encoding flagellin synthesis contains extended region, distinguishing B. anthracis strains from the majority of non-pathogenic and opportunistic bacilli. A novel method for the anthrax pathogen indication and identification based on determination of the differences in the chromosomal genes fliC and hom2 structure was suggested. A total of 60 strains of different Bacillus spp. (B. anthracis, B. cereus, B. thuringiensis, B. mycoides, B. megaterium, B. subtilis, etc.) were tested using two chromosomal DNA targets. The algorithm developed in this work permits to detect the pathogenic microorganism and reliably differentiate it from other Bacillus spp. representatives. The introduction of primers complementary to specific sequences of pXO1 and pXQ2 plasmids into the multiplex PCR makes it possible to receive additional information on proposed virulence of the isolate. PMID- 27192818 TI - [The Experience of the Identifying Rubella Infection Markers during Local Outbreaks in Western Siberia]. PMID- 27192819 TI - [ENHANCEMENT OF THE IMMUNE RESPONSE BY CO-DELIVERY OF THE HEPATITIS C VIRUS RECOMBINANT DNA AND PROTEINS OF REPLI- CATIVE COMPLEX GENETIC VARIANTS OF THE NOROVIRUS GENOTYPE GII.6]. AB - BACKGROUND: Noroviruses--etiological agents of acute enteric infections, mainly related to the genotype GII.4. However, other genotypes of the noroviruses also play an important role in some epidemic seasons or in particular geographic regions. The norovirus genotype GII.6 has become the second most important etiologic agent of outbreaks of the norovirus infection after GII.4 in recent years. OBJECTIVE: To characterize the norovirus genotype GII.6 genetic variants based on phylogenetic analysis of genome sequences submitted to the databases GenBank and NoroNet as well as identified in Nizhny Novgorod. MATERIALS AND METHODS: Norovirus genotype GII.6 circulating with sporadic morbidity that had caused the outbreak of acute enteric infection in Nizhny Novgorod were identified by sequencing the region of the genome encoding the N/S-domain of capsid protein VP1. The comparative phylogenetic analysis of obtained sequences and sequences available in the international genetic databases was performed using the MEGA 5.2 software package. RESULTS: The presence of three genetic variants of the noroviruses GII.6 genotype based on capsid protein gene, GII.6a (Seacroft_1990), GII.6b (Saitama_1997) and GII.6c (Shizuoka 2008), in combination with two genotypes of the polymerase gene, P6 and P7, was confirmed. It was shown that co circulation of these variants from the 1970s reflected the differences in evolution between the minor genotypes of noroviruses and dominant genotype GII.4, whose new epidemic variants completely replaced the previous for several years. Noroviruses GII.6 circulating in Nizhny Novgorod and other cities of Russia belong to genovariants GII.6a and GII.6b. CONCLUSION: The recombinant noroviruses GII.P7_GII.6c became most widespread in Asia and Europe in recent years. Genetic variant GII.6c of the norovirus have not been identified in Russia, but we cannot exclude the possibility of their occurrence as a cause of the outbreaks of acute enteric infections in this country in the near future. PMID- 27192820 TI - [TULA HANTAVIRUS IN CRIMEA]. AB - Genetic evidence of the Tula virus (TULV) in Crimea region of Russia is presented. Based on the reverse transcription PCR and subsequent sequence analysis, a total of 4 RNA isolates of the TULV were identified from the tissue samples of the Altai voles Microtus obscurus captured in the Bakhchisaray district of the Republic Crimea. Phylogenetic analysis of the S-, M-, and L segment sequences of the Crimean TULV strains showed that they formed distinct genetic lineage, Russia IV, in the TULV variant. New sequences were most closely related to the lineage Russia I sequences obtained from common vole (M. arvalis) captured in the Tula region in Central Russia PMID- 27192821 TI - [Dynamics of Irreversible Evaporation of a Water-Protein Droplet and a Problem of Structural and Dynamical Experiments with Single Molecules]. AB - We discuss the effect of isothermal and adiabatic evaporation of water on the state of a water-protein droplet. The discussed problem is of current importance due to development of techniques to perform single molecule experiments using free electron lasers. In such structure-dynamic experiments the delivery of a sample into the X-ray beam is performed using the microdroplet injector. The time between the injection and delivery is in the order of microseconds. In this paper we developed a specialized variant of all-atom molecular dynamics simulations for the study of irreversible isothermal evaporation of the droplet. Using in silico experiments we determined the parameters of isothermal evaporation of the water protein droplet with the sodium and chloride ions in the concentration range of 0.3 M at different temperatures. The energy of irreversible evaporation determined from in silico experiments at the initial stages of evaporation virtually coincides with the specific heat of evaporation for water. For the kinetics of irreversible adiabatic evaporation an exact analytical solution was obtained in the limit of high thermal conductivity of the droplet (or up to the droplet size of -100 A). This analytical solution incorporates parameters that are determined using in silico. experiments on isothermal droplet evaporation. We show that the kinetics of adiabatic evaporation and cooling of the droplet scales with the droplet size. Our estimates of the water-protemi droplet. freezing rate in the adiabatic regime in a vacuum chamber show that additional techniques for stabilizing the temperature inside the droplet should be used in order to study the conformational transitions of the protein in single molecules. Isothermal and quasi-isothermal conditions are most suitable for studying the conformational transitions upon object functioning. However, in this case it is necessary to take into account the effects of dehydration and rapid increase of ionic strength in an aqueous microenvironment surrounding the protein. PMID- 27192822 TI - [Protein Folding and Stability in the Presence of Osmolytes]. AB - Osmolytes are molecules with the function among others to align hydrostatic pressure between intracellular and extracellular spaces. Accumulation of osmolytes occurs in the cell in response to stress caused by pressure change, change in temperature, pH, and concentration of inorganic salts. Osmolytes can prevent native proteins denaturation and promote folding of unfolding proteins. Investigation of the osmolytes effect on these processes is essential for understanding the mechanisms of folding and functioning of proteins in vivo. A score of works, devoted to the effect of osmolytes on proteins, are not always consistent with each other. In this review an attempt was made to systemize available array of data on the subject and consider the problem of folding and stability of proteins in solutions in the presence of osmolytes from the single viewpoint. PMID- 27192823 TI - [Similarity of Spectral Profiles with Individual Fluorescence Lifetime of Tryptophan in Proteins of Different Structure]. AB - This work presents the results of the analysis of the fluorescence lifetime of tryptophan in three proteins: human serum albumin, bovine serum albumin and bacterial luciferase, containing 1, 2 and 7 tryptophan residues, respectively. It was shown that for all proteins fluorescence decay can be fitted by three lifetimes: tau1 = 6-7 ns, tau2 = -2,0-2,3 ns and tau3 <= 0,1 ns (the native state) and tau1 = 4,4-4,6 ns, tau2 = 1,7-1,8 ns and tau3 <= 0,1 ns (the denaturated state). It was found that spectral profiles with individual protein fluorescence lifetime have similar peak wavelength and identical half-width of the spectrum as in the native state (lambda(max)tau1 = 342 nm, lambda(max)tau2 = 328 nm and lambda(max)tau3 = 3i5 nm), and in the denaturated state (lambda(max)tau1 = 350 nm, lambda(max)tau2 = 343 nm and lambda(max)tau3 = 317 nm). In addition, the differences in the steady-state spectra of the studied proteins are caused by the individual ratio of lifetime contributions. The correlation between. lifetime components and a known classification of the tryptophan residues in the structure of proteins, under study was performed within the discrete states model. PMID- 27192824 TI - [Magnetic Magnesium Isotope Accelerates ATP Hydrolysis Catalyzed by Myosin]. AB - In this paper, we present the results of experimental studies on the influence of different magnesium isotopes, the magnetic 25Mg and nonmagnetic 24Mg and 26Mg on ATP activity of the isolated myosin subfragment-1. The reaction rate in the presence of magetic 25Mg isotope turned out to be 2.0-2.5 times higher than that using nonmagnetic 24Mg and 2 Mg isotopes. No magnetic isotope effect was observed in the absence of the enzyme as in spontaneous ATP hydrolysis in aqueous solution. Hence, a significant catalytic effect of the magnetic 25Mg isotope (nuclear spin catalysis) was observed in the enzymatic hydrolysis of ATP. PMID- 27192825 TI - [Structure and Activity of Fungal Lipases in Bile Salt Solutions]. AB - The changes in structure and catalytic properties of fungal lipases (Candida rugosa, Rhizomucor miehei, Mucor javanicus) were investigated in micellar solutions of bile salts that differ in hydrophilic-lypophilic balance and reaction medium properties. The methods of circular dichroism and tryptophan fluorescence were applied to estimate the changes in peptide structure within complexes with bile salt micelles. Bile salts do not exert a significant influence on the structure of the enzymes under study: in Rh. miehei and M. javanicus lipases the alpha helix content slightly decreased, the influence of bile salts on the C. rugosa structure was not revealed. Despite negligible structural modifications in the enzymes, in bile salt solutions a considerable change in their catalytic properties was observed: an abrupt decrease in catalytic effectiveness. Substrate-bile salts micelles complex formation was demonstrated by the NMR self-diffusion method. The model of a regulation of fungal lipase activity was proposed. PMID- 27192826 TI - [On a Possible Mechanism of the Effect of Microwave Radiation on Biological Macromolecules]. AB - A model describing the process of dissociation of hydrogen bonding in water clusters when irradiated by electromagnetic field in the microwave range is suggested. The model is also applicable for the case of rupture of the covalent bond of the water molecule cluster. If the energy absorption occurs at the interface of water and polymer clusters (e.g., DNA, chitosan), degradation of the polymer chain is possible. PMID- 27192827 TI - [Analysis of Conformational Features of Watson-Crick Duplex Fragments by Molecular Mechanics and Quantum Mechanics Methods]. AB - It is generally accepted that the important characteristic features of the Watson Crick duplex originate from the molecular structure of its subunits. However, it still remains to elucidate what properties of each subunit are responsible for the significant characteristic features of the DNA structure. The computations of desoxydinucleoside monophosphates complexes with Na-ions using density functional theory revealed a pivotal role of DNA conformational properties of single-chain minimal fragments in the development of unique features of the Watson-Crick duplex. We found that directionality of the sugar-phosphate backbone and the preferable ranges of its torsion angles, combined with the difference between purines and pyrimidines. in ring bases, define the dependence of three dimensional structure of the Watson-Crick duplex on nucleotide base sequence. In this work, we extended these density functional theory computations to the minimal' fragments of DNA duplex, complementary desoxydinucleoside monophosphates complexes with Na-ions. Using several computational methods and various functionals, we performed a search for energy minima of BI-conformation for complementary desoxydinucleoside monophosphates complexes with different nucleoside sequences. Two sequences are optimized using ab initio method at the MP2/6-31++G** level of theory. The analysis of torsion angles, sugar ring puckering and mutual base positions of optimized structures demonstrates that the conformational characteristic features of complementary desoxydinucleoside monophosphates complexes with Na-ions remain within BI ranges and become closer to the corresponding characteristic features of the Watson-Crick duplex crystals. Qualitatively, the main characteristic features of each studied complementary desoxydinucleoside monophosphates complex remain invariant when different computational methods are used, although the quantitative values of some conformational parameters could vary lying within the limits typical for the corresponding family. We observe that popular functionals in density functional theory calculations lead to the overestimated distances between base pairs, while MP2 computations and the newer complex functionals produce the structures that have too close atom-atom contacts. A detailed study of some complementary desoxydinucleoside monophosphate complexes with Na-ions highlights the existence of several energy minima corresponding to BI-conformations, in other words, the complexity of the relief pattern of the potential energy surface of complementary desoxydinucleoside monophosphate complexes. This accounts for variability of conformational parameters of duplex fragments with the same base sequence. Popular molecular mechanics force fields AMBER and CHARMM reproduce most of the conformational characteristics of desoxydinucleoside monophosphates and their complementary complexes with Na-ions but fail to reproduce some details of the dependence of the Watson-Crick duplex conformation on the nucleotide sequence. PMID- 27192828 TI - [Interaction of Dystamycin Dimeric Analog with Poly(dA) x poly(dT), Poly[d(A-T)] x poly[d(A-T)] and Duplex O23 at Origin of Replication of the Herpes Simplex Virus]. AB - The binding of distamycin dimeric analog (Pt-bis-Dst) to poly[d(A-T)] x poly[d(A T)1, poly(dA) x poly(dT) and duplex O23 with the sequence 5' GCCAATATATATATATTATTAGG-3' which is present at the origin of replication of herpes simplex virus OriS is investigated with the use of UV and CD spectroscopy. The distinction of the synthetic polyamide from a natural antibiotic lies in the fact that in the synthetic polyamide there are two distamycin moieties bound via a glycine cis-diamino platinum group. It was shown that the binding of Pt-bis-Dst to poly[d(A-T)] x poly[d(A-T)] and poly(dA) x poly(dT) reaches saturation if one molecule of the ligand occurs at approximately every 8 bp. With further increase in the ratio of the added ligand to the base pairs in CD spectra of complexes with poly[d(A-T)] x poly[d(A-T)], we observed that the maximum wavelength band tend to be shifted towards longer wavelengths, while in the spectral region of 290-310 nm a "shoulder", that was absent in the spectra of the complexes obtained at low polymer coverages by the ligand, appeared. At high molar concentration ratios of ligand to oligonucleotide Pt-bis-Dst can bind to poly[d(A-T)] x poly[d(A-T)] in the form of hairpins or may form associates by the interaction between the distamycin moieties of neighboring molecules of Pt-bis-Dst. The structure of the complexes is stabilized by interactions between pirrolcarboxamide moieties of two molecules of Pt-bis-Dst adsorbed on adjacent overlapping binding sites. These interactions are probably also responsible for the concentration-dependent spectral changes observed during the formation of a complex between Pt-bis-Dst and poly[d(A-T)] x poly[d(A-T)]. Spectral changes are almost absent in binding of Pt-bis-Dst to poly(dA) x poly(dT). Binding of Pt-bis Dst to duplex O23 reaches saturation if two ligand molecules occur in a duplex that contains a cluster of 18 AT pairs. With increasing the molar concentration ratio of the ligand to the duplex CD spectra undergo concentration-dependent changes similar to those observed during binding of Pt-bis-Dst to poly [d(A-T)] x poly[d(A-T)]. Testing for antiviral efficacy of Pt-bis-Dst showed that the concentration, at which the cytopathic effect produced by the herpes simplex virus in cell culture Vero E6 halved, is equal to 1.5 MUg/ml and the selectivity index for evaluating antiviral activity is 65 at a relatively low cytotoxicity. The concentration of Pt-bis-Dst, at which approximately half the cells are killed, is equal to 100 MUg/ml. PMID- 27192829 TI - [Determination of the Minimal Fragment of the Poliovirus IRES Necessary for the Formation of a Specific Complex with the Human Glycyl-tRNA Synthetase]. AB - Aminoacyl-tRNA synthetases are an ancient enzyme family that specifically charge a tRNA molecule with a cognate amino acid required for protein synthesis. Glycyl tRNA synthetase is one of the most interesting aminoacyl-tRNA synthetases due to its structure variability and functional features in the different organisms. It was shown recently that human glycyl-tRNA synthetase is a regulator of translational initiation of poliovirus mRNA. Details of this process and its mechanism still remain unknown. While exploring this stage of poliovirus functioning we have studied the interaction of the cytoplasmic form of human glycyl-tRNA synthetase and its domains with the fragments of the poliovirus IRES element. As a result, we have identified the minimal fragment of viral mRNA with which glycyl-tRNA synthetase fully interacts and estimated the contribution of some domains to the interaction of glycyl-tRNA synthetase with RNA. PMID- 27192830 TI - [Forced Oscillations of DNA Bases]. AB - This paper presents the results of the studying of forced angular oscillations of the DNA bases with the help of the mathematical model consisting of two coupled nonlinear differential equations that take into account the effects of dissipation and the influence of an external periodic field. The calculation results are illustrated for sequence of gene encoding interferon alpha 17 (IFNA 17). PMID- 27192831 TI - [Gelation in Low Concentrated Solutions of Cholesterol and Ergosterol]. AB - The molecular dynamics method has been applied to investigate the conformational behavior of biologically important chiral molecules of cholesterol and ergosterol. The formation of strings in the solution of cholesterol in methanol and the lack of strings in solutions of ergosterol in methanol has been experimentally detected. It was shown that the intermolecular dynamics in the molecule has a significant impact on the potential of structure formation. We proposed alternative explanation of the functional significance of cholesterol, apparently associated with the formation of interconnect structures outside the membrane as the biological feasibility of finding ergosterol in non-switched cells of fungi and cholesterol in the switching cells of macroorganisms. PMID- 27192832 TI - [Generation of Superoxide Radicals by Complex III in Heart Mitochondria and Antioxidant Effect of Dinitrosyl Iron Complexes at Different Partial Pressure of Oxygen]. AB - The EPR spin-trapping technique and EPR-oximetry were used to study generation of superoxide radicals in heart mitochondria isolated from Wistar rats under conditions of variable oxygen concentration. Lithium phthalocyanine and TEMPONE 15N-D16 were chosen to determine oxygen content in a gas-permeable capillary tube containing mitochondria. TIRON was used as a spin trap. We investigated the influence of different oxygen concentrations in incubation mixture and demonstrated that heart mitochondria can generate superoxide in complex III at different partial pressure of oxygen as well as under the conditions of deep hypoxia (< 5% O2). Dinitrosyl iron complexes with glutathione (the pharmaceutical drug "Oxacom") exerted an antioxidant effect, regardless of the value of the partial pressure of oxygen, but the magnitude and kinetic characteristics of the effect depended on the concentration of the drug. PMID- 27192834 TI - [Influence of Storage Temperature and Cryopreservation Conditions on the Extent of Human Sperm DNA Fragmentation]. AB - With the direct labeling procedure for detecting DNA fragmentation we explored the influence of the different storage temperature conditions as well as different methods of cryopreservation on the structure of DNA organization in the human sperm. 19 sperm samples obtained from healthy men with normozoospermia (according to the criteria of the World Health Organization) were used for investigation. A significant increase of human sperm DNA-fragmentation was observed after 8 hours of incubation at +39 degrees C (by 76.7%) and at +37 degrees C (by 68.9%). It was found that sperm cooling with the use of a cryoprotectant immediately after thawing did not produce significant differences in the extent of DNA fragmentation, although samples, containing cryoprotectants, showed a sharp increase of DNA fragmentation after 24 hours of incubation, that could suggest cryoprotectant cytotoxicity. PMID- 27192833 TI - [The Nonlinear Effect of the Composite Influence of Red and Blue Light on Bacteria Escherichia coli Viability]. AB - A non-linear dependence of the inhibition of E. coli cells is found when irradiated simultaneously with the blue and red regions of the spectrum at a power density of 100 mW/cm2. Such dependence is explained by the assumption of a cascade two-photon absorption of light by DNA molecules with an intermediate resonance at cellular chromophores, causing excitation and subsequent DNA damage similar to damage when exposed to UV radiation. PMID- 27192835 TI - [The Role of ABCG2 Protein in Maintenance of Viability and Proliferative Activity of Bone Marrow Mesenchymal Stem Cells Under Hypoxic Conditions]. AB - It has been shown that hypoxia (5% 02) and fibroblast growth factor bFGF reduce the doubling time of bone marrow mesenchymal stem cells under their cultivation in vitro that indicates an increase in cell culture proliferation. It has been found out that low concentrations of O2 and factor bFGF added to the cell culture medium increase an expression of abcg2 gene and its gene protein, ABCG2 transport gene, in mesenchymal stem cells. These events potentiate the effects of hypoxia observed in mesenchymal stem cells. We revealed that blocking of ABCG2 protein functional activity led to increased generation of reactive oxygen species in mesenchymal stem cells. The effect of hypoxia and/or bFGF on protein profile of mesenchymal stem cells was studied. The results represented in this work together with previous data proved a link between ABCG2 protein expression, its activity and maintenance of viability and proliferative activity of mesenchymal stem cells cultivated under hypoxia. ABCG2 acts as protector. PMID- 27192836 TI - [The Role of Membrane-Bound Heat Shock Proteins Hsp90 in Migration of Tumor Cells in vitro and Involvement of Cell Surface Heparan Sulfate Proteoglycans in Protein Binding to Plasma Membrane]. AB - Heat shock protein Hsp90, detected in the extracellular space and on the membrane of cells, plays an important role in cell motility, migration, invasion and metastasis of tumor cells. At present, the functional role and molecular mechanisms of Hsp90 binding to plasma membrane are not elucidated. Using isoform specific antibodies against Hsp90, Hsp9alpha and Hsp90beta, we showed that membrane-bound Hsp90alpha and Hsp90beta play a significant role in migration of human fibrosarcoma (HT1080) and glioblastoma (A-172) cells in vitro. Disorders of sulfonation of cell heparan sulfates, cleavage of cell heparan. sulfates by heparinase I/III as well as treatment of cells with heparin lead to an abrupt reduction in the expression level of Hsp90 isoforms. Furthermore, heparin significantly inhibits tumor cell migration. The results obtained demonstrate that two isoforms of membrane-bound Hsp90 are involved in migration of tumor cells in vitro and that cell surface heparan sulfate proteoglycans play a pivotal role in the "anchoring" of Hsp90alpha and Hsp90beta to the plasma membrane. PMID- 27192837 TI - [Changes in Kinetics of Chemiluminescence of Plasma as a Measure of Systemic Oxidative Stress in Humans]. AB - Oxidative stress is a pathogenetic factor of many diseases. The control of its level is important for early diagnosis and therapy adjustment. In this work, antioxidant status was estimated in blood plasma. In the system of 2,2'-azo-bis(2 amidinopropane)dihydrochloride-luminol a set of chemiluminescence kinetic curve parameters is proposed for oxidative stress level estimation (the latent period tau(lat) and the increasing of analytical signal DeltaI(CL)). Uric acid and albumin were shown as the main components that responsible for changes in chemiluminescence kinetic curve of plasma. Serum albumin undergoes oxidative modification in dose-depend manner under the action of UV irradiation, it causes the enhancement of antioxidant properties. Changes in plasma chemiluminescence kinetics are proposed as a measure of oxidative stress in human body. PMID- 27192839 TI - [Mechanism of Formation of Cardiac Arrhythmia Due to Pathological Distribution of Myocardium Conductivity]. AB - Two mechanisms responsible for the emergence of arrhythmia are known: a change of part of the cells to a self-oscillatory mode and generation of circulating waves. In this paper, we investigate the generation mechanism of the circulating waves using the unidirectional block. One of the variants of its realization is a narrow gap between two non-conducting regions. Implementation of this mechanism in the human heart turns out to be impossible, since in the heart in which the duration of cardiac action potential lasts 0.3 s and the velocity of wave propagation is equal to 33 cm/s, the minimal length of the pathway for wave circulation is approximately 10 cm, while the distance between the ventricular apex and atrioventricular septal is, on the average, 8 cm. Therefore, that inhomogeneity cannot exist at the scale of human heart. To adapt this mechanism to the size of the human heart, we introduce into the scheme the regions with low conductivity, which provide slow propagation of the wave. The value of conductivity is chosen based on the results of evaluation of the "conductivity wave velocity" correlation. The analysis of wave propagation through the boundary between two regions with different conductivities has shown that the refractory period depends on the conductivity ratio. To minimize this dependence we introduce the transition zone, in which conductivity changes linearly from some normal value to a reduced one. This allowed us to generate a 12-mm inhomogeneity area, provoking the appearance of the circulating wave. PMID- 27192838 TI - [Nitric Oxide in Modulation of Crystallogenic Propeties of Biological Fluid]. AB - The aim of this work was a comparative analysis of the influence of different NO forms on dehydration structurization of human blood serum. Blood specimens from 15 healthy people were treated by NO-containing gas flow (800 and 80 ppm) generated with the "Plazon" unit, experimental NO-generator (20, 50, 75 and 100 ppm) and by water solution of thiol-containing dinitrosyl iron complexes (3 mM/L). The influence of blood sodium on blood serum crystallization in original and NO-treated blood specimens was estimated. It was found, that the effect of NO on crystallogenic properties of blood serum depends directly on its concentration and form (free or bound), as well as on the presence of reactive oxygen species in gas flow. The most pronounced stimulating effect was observed for the bound form of NO--dinitrosyl iron complexes with glutathione ligands. Low NO concentrations modulated crystallogenic properties of blood serum and the most optimal stimulating action was demonstrated in gas flow containing 20 ppm nitric oxide. In contrast, high NO concentration (800 ppm) inhibited the crystallogenic activity of biological fluid with multiply increasing of structural elements destruction leading to the formation of an additional belt in marginal zone of dehydrated specimens. PMID- 27192841 TI - [Neurodynamic Bases of Imitation Learning and Episodic Memory]. AB - In this review, three essentially important processes in development of cognitive behavior are considered: knowledge of a spatial environment by means of physical activity, coding and a call of an existential context of episodic memory and imitation learning based on the mirror neural mechanism. The data show that the parietal and frontal system of learning by imitation, allows the developing organism to seize skills of management and motive synergies in perisomatic space, to understand intentions and the purposes of observed actions of other individuals. At the same time a widely distributed parietal and frontal and entorhinal-hippocampal system mediates spatial knowledge and the solution of the navigation tasks important for creation of an existential context of episodic memory. PMID- 27192840 TI - [Some Approaches to Activation of Antitumor Resistance Mechanisms and Functional Analogs in Categories of Synergetics]. AB - This paper briefly reviews the ways of activation of the antitumor resistance mechanisms developed on the basis of the concept of the periodic system of general nonspecific adaptational reactions of the body. The principles of the formation of effective influences by electromagnetic radiation using biologically active substances are described. A comparison of the criteria and conceptions of the theory of adaptational reactions to some concepts and categories of synergetics is made. The features of dynamics of the studied parameters upon effective influences are considered. Antistress nature of the systemic effects of ferromagnetic nanoparticles on tumor bearing animals is shown. The, possible mechanisms of regression of large tumor under the influence of two different factors--modulated electromagnetic radiation and magnetite nanoparticles--are discussed. The cases of a change of the order parameter in connection with the development of antistress areactivity and regression of experimental tumors under the influence of the combined electromagnetic impact are analyzed. PMID- 27192843 TI - [An Iterative Continuous-Event Model of the Population Outbreak of Phytophagous Hemiptera]. AB - Based on the analysis of changes in the local density of the insect within the family Psillidae in Australia we have developed a model for a scenario of a dramatic increase in the number of jumping plant lice at the expense of primary and secondary Encyrtidae parasitoid microwasps. A phenomenological model describes on a case by case basis the efficiency of reproduction in several ranges of population conditions. We have proposed a continuous-event structure, where the rate of a decrease of the number of psyllid generations is uneven at different stages of ontogenesis of the insect with an incomplete metamorphosis. The moments when the rate is changing are determined by the state of internal variables of the auxiliary equation of a continuous system. Spontaneous time limited local outbreak occurs after overcoming the threshold balancing in iterative dynamic system that reduces the effect of normal regulatory mechanisms of psyllid reproduction and the speed of a decrease of the number of generations changes. The method with the addition of the right side of the first equation by special functionality with limited range of values simulates a sharp decrease in survival with the exhaustion of resources. The limited availability of leaves causes a backward tangent bifurcation. After a few iterations from the tangent bifurcation population transfers to the mode of ordinary fluctuations without explicit of cyclical component at a low average psyllids population. PMID- 27192842 TI - [Providing the Optimal Insolation of a Photobiological Architectural Shell for Microalgae Cultivation]. AB - Translucent architectural shells with microalgae are considered as an element of local photobiological treatment facilities integrated in the urban environment. A mathematical microalgae growth model for the prediction of insolation and temperature behaviour in the medium during microalgae cultivation under dynamically fluctuating natural lighting is presented. The task of optimizing the parameters of photobiological architectural shell with respect to temperature and insolation is set. The results of numerical experiments for the model problem are shown. PMID- 27192844 TI - [On Atomic Nuclear Fusion Processes at Low-Temperatures. An Enhancement of the Probability of Transition through a Potential Barrier Due to the So-Called Barrier Anti-Zeno Effect]. AB - It is known that in quantum mechanics the act of observing the experiment can affect the experimental findings in some cases. In particular, it happens under the so-called Zeno effect. In this work it is shown that in contrast to the "standard" Zeno-effect where the act of observing a process reduces the probability of its reality, an inverse situation when a particle transmits through a potential barrier (a so-called barrier anti-Zeno effect) can be observed, the observation of the particle essentially increases the probability of its transmission through the barrier. The possibility of using the barrier anti-Zeno effect is discussed to explain paradoxical results of experiments on "cold nuclear fusion" observed in various systems including biological ones. (According to the observers who performed the observations, the energy generation, which could not be explained by any chemical processes, as well as the change in the isotope and even element composition of the studied object may occur in these systems. PMID- 27192845 TI - [ASSESSMENT OF LIVER FUNCTION WITH TRANSESOPHAGEAL ECHOCARDIOGRAPHY HEART SURGERY WITH CARDIOPULMONARY BYPASS]. AB - AIM OF THE STUDY: evaluation of arterial and venous liver circulation during cardiopulmonary bypass (CPB) using the method of transesophageal echocardiography (TEE). MATERIALS AND METHODS: 62 patients undergoing reconstructive cardiac surgery with CPB were analyzed. During all the stages of treatment we performed monitoring of mean arterial pressure, heart rate and central venous pressure. TEE was performed using specialized Philips iE-33 3-D matrix multifrequency probe X7 2t in transgastral position. Ultrasonic and dopplerographic measuring of blood flow in hepatic artery and veins was performed before sternotomy, in 30 minutes after starting CPB and after stopping CPB during sternal closure. The speed of bloodflow in hepatic artery, hepatic veins, biochemical blood analysis was evaluated, i.e. lactate level, AST ALT ratio before the intervention, during CPD and in early postoperative period RESULTS: Correlation between blood flow in liver vessels and dynamics of biochemical analysis. It is considered to that this change during procedures with CPB may be linked with liver insufficiency during first hours of evaluation. In other words reduced blood flow in liver vessels may be one of the liver insufficiency early symptoms and is one of factors that require correction during operative and early postoperative period. So dynamic follow-up of hepatic circulation may be used as a method of early diagnostics of functional organ disorders. PMID- 27192846 TI - [THE INFLUENCE OF ANAESTHESIA ON PERIOPERATIVE VALUES OF AMINOTERMINAL FRAGMENT OF THE BRAIN NATRIURETIC PEPTIDE PRECUSSOR IN PATIENT WITH POSTINFARCTION CARDIOSCLEROSIS UNDERGOING NONCARDIAC SURGERY]. AB - BACKGROUND: The importance of postoperative values of cardiac damage biomarkers studying (such as troponine and NTproBNP) is stressed by recommendations of the European Society of Cardiology and the European Society of Anaesthesiologists (2014). AIM OF THE STUDY: the effects of general and spinal anaesthesia on perioperative dynamics of NTproBNP in patients with postinfarction cardiosclerosis in the surgical treatment of benign prostatic hyperplasia. MATERIALS AND METHODS: 67 men aged 60 to 75 years were included in a prospective, randomized study. Patients were undergone elective open surgery for prostatic hyperplasia. All patients had a history of myocardial infarction. Depending on the type of anaesthesia the patients were divided into 2 groups: The first group (35) was operated under spinal anaesthesia (SA). The second group (32) was operated under general anaesthesia (GA). The volume infusion was 2700 +/- 250 ml in the first group and 1600 +/- 250 ml in the second group during perioperative period. Determining the level of NTproBNP in the venous blood plasma realized four times: 1 hour before surgery, at once at the end of surgery, 12 and 24 hour after surgery. RESULTS: The first group patients was registered an increase the values of NTproBNP in plasma 2 times from 628.6 +/- 107.4 pg/mol to 1204.1 +/- 141.9 pg/mol 12 hour after the operation (P < 0.01). After 24 hours the level of NTproBNP in blood plasma of the first group patients was reduced by 28%, but, however, exceeding the values in the second group is more than 1.7 times (P < 0.05). CONCLUSION: The extra volume of the infusion during the spinal anaesthesia in the early postoperative period after the elimination of the sympathetic blockade to leads volume overload in patients with accompanying cardiac pathology. PMID- 27192847 TI - [ANALYSIS OF THE POSTOPERATIVE COURSE OF COMPLEX CONGENITAL HEART DISEASES SIMULTANEOUS CORRECTION WITH AN OPEN STERNOTOMY IN CHILDREN DURING THE FIRST MONTHS OF LIFE]. AB - In children during the first months of life delayed sternum closure is one of the few techniques increasing cardiac output after simultaneous correction of complex congenital heart defects (CHD). The aim of study was evaluating mortality, predictors of adverse outcome and frequency noncardial complications at of delayed sternum closure after correction of CHD. METHODS: Study design: a prospective, uncontrolled, cohort. 22 children were studied 6 children died. Anesthesia was carried out on the basis ofpropofol (3 mg/kg/h) and fentanyl (5 pg/kg/h) infusion with sevoflurane inhalation in a dose of 1-1.5 WT, including during perfusion. Cardiopulmonary bypass (IR) was carried out by the "Stockert S50" using oxygenators ("Medtronic"). After IR in all cases the use of arterio- venous modified ultrafiltration. Sternum closure was performed on average 2.7 +/- 1.4 days after surgery. RESULTS: The odds ratio (OR) of death development at the mean arterial pressure (MAP) < 35 Hg was 3.7, the OR for the risk of death development if SVO2 < 40% was 0.94. OR for risk of death when blood lactate level > 10 mmol/l during the first three days ofpostoperative intensive care was 2.1. CONCLUSIONS: The technique of delayed sternum closure is an acceptable method of maintaining cardiac output in children during the first months of life with CHD in the postoperative period. High blood lactate level (> 10 mmol/l) and especially its further growth and the MAP < 35 mm Hg can be predictors of adverse outcomes of surgical interventions with an open sternotomy. PMID- 27192848 TI - [CAUSES AND PREVENTION OF POSTOPERATIVE NAUSEA AND VOMITING AFTER ADENOTONSILLECTOMY IN CHILDREN IN THE GENERAL ANESTHESIA]. AB - The aim of the research is to determine the reasons of post operative nausea and vomiting and to compare the efficiency of taken PONVprophylaxis after adenotonsillectomy with general anesthesia in children. 155 patients took part in the research work at the age from 3 to 10 years, of ASAI-II physical status, who were operated on in planned order because of adenotonsillectomy. The patients were divided into 5 groups according to the type of holding PONV prophylaxis. The 1-st group consisted of 30 patients who were given antiemetic--Metoclopramidum (0.15 mg/kg); the 2-nd group (30 patients) was given ondansetronum (0.1 mg/kg); the 3-d group also consisted of 30 patients who were given Dexamethasone (0.2 mg/kg, but not more than 8 mg); the 4-th included 30 patients who were given Dexamethasone (0.2 mg/kg, but not more than 8 mg) and Metoclopramidum (0,15 mg/kg) as the antiemetic; the 5-th group the test one, included 35 patients who were not given PONVprophylaxis. During the first day after the operation the amount of nausea and vomiting have been estimated, the time of occurrence and the character of vomiting. According to the results of the research the PONV in postoperative period consisted 22.6% in which in 13.6% vomiting with blood was pointed out during coming out from general anesthesia, and in early post operative period (p < 0.01), which is connected with blood swallowing on the phase of awaking or possible postoperative bleeding. According to given prophylaxis the least number of PONV is revealed in the group which was given ondansetronum, and the high frequency of post operative nausea and vomiting was pointed out in the group which wasn't given prophylaxis of PONV. PMID- 27192849 TI - [THE COGNITIVE STATUS DYNAMIC OF CARDIOSURGICAL PATIENTS AND THE PREDICTORS OF ITS DISTURBANCE]. AB - AIM OF RESEARCH: To estimate the cognitive status dynamics ofpatients during the early postoperative period after cardiac interventions and to reveal predictors of cognitive functions deterioration at this category of patients. MATERIALS AND METHODS: 118 cardiac patients were tested of neurocognitive functions one days before operation, and then for the 2-3rd days after operation by means of the MMSE test, the FAB test, Shulte's test, a questionnaire of a depression of CES-D, the BATTERY OF FRONTAL DYSFUNCTION TEST. Data of the perioperation's period was analyzed. RESULTS: Deterioration of results in the 2nd and more tests were registered at 61% of patients. The main distinctions between patients with postoperative deterioration of testing results and without it were: parameters of mehanical ventilation (tidal volume/ideal body weight, airways pressure), initial condition and existence of signs of initial deficit of blood circulation (decrease in the cardiac index and O2 delivery, increase of level of a lactate), decrease in cerebral oksimetry, existence of respiratory alkalosis dekompensation during CPB. Administration of the Dopamine before CPB and use of Desfluran demonstrated the positive influence to the cognitive status. CONCLUSIONS: 1) Neurocognitive dysfunction during the early postoperative period after cardiac surgery is tipical for 30-70% of patients. 2) The most significant predictors of deterioration of neurocognitive function in the postoperative period are the excessive depth of anesthesia and significant intraoperative decrease in the cerebral oxygenation. 3) Influence of the mehanical ventilation parameters on postoperative neurocognitive function is revealed, use of the large tidal volumes is especially negative. 4) Existence of the blood circulation deficit and decrease in oxygen delivery without timely intraoperative correction, and also an intraoperative hyperglycemia worsen a neurocognitive function in the postoperative period. 5) Desfluran administration has positive impact on the neurocognitive function. PMID- 27192851 TI - [FEATURES OF FLUID THERAPY IN CHILDREN WITH SEVERE MAJOR TRAUMA]. AB - BACKGROUND: Fluid and transfusion therapy is proved to be a required component of treating children with severe major trauma significantly influencing the case outcome. OBJECTIVE: To analyze efficiency of fluid and transfusion therapy in children with severe major trauma and assess its correspondence with current recommendations. MATERIALS AND METHODS: 150 children aged from 0 to 18 years getting treatment in intensive care units of children's city hospitals of Saint Petersburg, Archangelsk, Ufa, Samara, and Leningrad region were included in the research. The main course of severe major trauma were car injury and catatrauma. The coefficient according to Pediatric trauma score (PTS) was 6.4 points. The mean duration of hospitalization in emergencies units was 3 (2-7) days, the duration of artificial lung ventilation was 48 +/- 99.9 hours, the duration of hospitalization in the department ward was 24 (15-32) days. Favorable outcome (transferring from emergencies units to department wards) was reported in 147 (98%) children, death cases were registered in 4 (2.6%) children. RESULTS: There was determined that the basic crystalloid solutions used for infusion therapy in children were the following: Ringer solution, Plasma-lit solution and 10% glucose solution. "Gelofisin" and "Voluven" had more frequent administration rate among colloidal solutions. Transfusion of blood was performed in 26% patients. The infusion therapy in the first three days did not exceed the necessary physiological requirements that provided stabilization of the patient's condition and did not produce a negative influence on the status of hemodynamics and gas exchange. CONCLUSION: Administration of current well-balanced crystalloid and colloidal solutions to children with severe combined trauma in an amount within the limits of required physiological indicators does not produce a negative influence on the status of gas exchange and the case outcome. PMID- 27192852 TI - [MONITORING OF HEMODYNAMICS IN THE CHOICE OF INTENSIVE THERAPY IN THE OPERATED INFANTS]. AB - Noninvasive monitoring in obtaining important and reliable information relevant to pediatric practices, not only in respect of dangers and complications of most invasive techniques, but also because a number of them difficult or even impossible in infants. The aim of this study was to estimate the significance of hemodynamic parameters and capabilities of ECHO and dophlercardiography for analyzing violations hemodynamics in primary diagnosis and conduct drug therapy in infants. The study included the results of a survey of 65 infants aged from 29 to 39 weeks with various surgical pathology, who received the various options the hemodynamic support. In the initial assessment and selecting tactics of therapy for hemodynamic analysis carried out routine monitoring and for evaluation of cardiac contractility used echo- and Doppler exams. All children have pointed out a number of significant changes of haemodynamics, that has required inotropic therapy with dopamine (64% of children with diaphragmatic hernia received additional dobutamine). Validation of expressed pulmonary hypertension children appointed sildenafil, and in the absence ofthe effect used nitrous oxide. Hemodynamic monitoring allows to monitor the status of circulation on the background of the treatment and to make timely changes to the script therapy. PMID- 27192850 TI - [CHARACTERISTICS OF COMBINED ANESTHESIA WITH EPIDURAL COMPONENTE DEPENDING ON VEGETATIVE NERVOUS SYSTEM TYPE]. AB - The research objective was to study the characteristics of combined anesthesia with epidural componente (CAEC) depending on vegetative nervous system type (VNS) in patients who underwent large scale traumatic surgical operations on abdominal cavity organs. The scientific research was conducted in Anaesthesiology- Reanimation Department of the Scientific Surgical Centre named after acad. MA. Topchubashev, the Ministry of Health of the Azerbaijan Republic. The research objects were 69 patients who underwent operations in conditions of CAEC due to different serious surgical pathologies of abdominal cavity organs. VNS type was identified based on electroencephalogram, Cerdo Vegetative Index (CVI), Hildebrandt coefficient (HC) and single neurophysiological tests. The patients were divided into three groups depending on VNS type: I--normotonics--17 patients (24.7%), II--sympathatonics--25 patients (36.2%), and III--vagotonics--27 patients (39.1%). Blood adrenocorticotropic hormone (ACTH) and cortisol concentration were studied in 3 stages: I -preoperative, II--operation traumatic stage, III--the 1st postoperative days. The other indicators (heart rate, systolic blood pressure--SBP, dyastolic blood pressure--DBR average blood pressure--BP ave., pulse oximetry SpO2, ECG, gases in blood and acid-base balance, electrolytes, blood glucose level, myocardium oxygen demand--MOD) were registered after 20 minutes and the 2nd day after operation besides the above stages. The research results indicated that it is possible to define the vegetative nervous system type superiority based on complex of single tests data, EEG, ECG, Cerdo Vegetative Index, Hildebrandt coefficient. CAEC can be considered optimun alternative of general anesthesia ensuring neurohumoral and hemodynamic stability in large scale, traumatic operations on abdominal cavity organs. Clinical course of CAEC is characterized by firmer hemodynamic and humoral stability in patients with functional balance of sympathetic and parasympathetic divisions of vegetative nervous system, that is in normotonics in comparison with sympathico-, and parasympathotonics. PMID- 27192853 TI - [SIMULTANEOUS MEASUREMENT OF INTRAVENTRICULAR AND PARENCHYMAL INTRACRANIAL PRESSURE IN PATIENTS WITH SEVERE TRAUMA BRAIN INJURY]. AB - INTRODUCTION: "Standard" assessment of ICP by measuring liquor ventricular pressure recently questioned. THE OBJECTIVE OF THE STUDY: Compare the values of ventricular and parenchymal ICP against the closure of open liquor drainage and during active CSF drainage. MATERIALS AND METHODS: Examined 7 patients with TBI and intracranial hypertension syndrome, GCS 5.6 +/- 1.2 points, 4.2 +/- age 33 years. Compared parenchymal and ventricular ICP in three time periods: 1--during closure of ventricular drainage, 2--during of the open drains and drainage at the level of 14-15 mmHg, 3--during the period of active drainage. When comparing two methods of measurement used Bland-Altman method. RESULTS: 1. During time period of the closed drainage correlation coefficient was r = 0.83, p < 0.001. Bland Altman method: the difference of the two measurements is equal to the minimum and 0.7 mm Hg, the standard deviation of 2.02 mm Hg 2. During time period of the open drainage was reduction of the correlation coefficient to r = 0.46, p < 0.01. Bland-Altman method: an increase in the difference of the two measurements to 0.84 mmHg, standard deviation 2.8 mm Hg 3. During time period of the active drainage of cerebrospinal fluid was marked difference between methods of measurement. Bland-Altman method: the difference was 8.64 mm Hg, and a standard deviation of 2.6 mm Hg. CONCLUSIONS: 1. During the closure of the ventricular drainage were good correlation between ventricular and parenchymal ICR 2. During open the liquor drainage correlation between the two methods of measuring the intracranial pressure is reduced. 3. During the active CSF drainage correlation between the two methods of measuring intracranial pressure can be completely lost. Under these conditions, CSF pressure is not correctly reflect the ICP 4. For an accurate and continuous measurement of intracranial pressure on the background of the active CSF drainage should be carried out simultaneous parenchymal ICP measurement. PMID- 27192855 TI - [MECHANISMS OF SMALL INTESTINE MOTOR DISORDERS DURING ENDOTOXEMIA AND PATHOPHYSIOLOGICAL RATIONALE FOR THE USE OF TRIBUTYRINE AS ANTI-INFLAMMATORY AND PROKINETIC PHARMACONUTRIENT]. AB - Studying the mechanisms of the small intestine motor function disorders during endotoxemia and searching ways to mitigate them remain relevant. The article discusses the role of inflammatory mediators, in particular nitric oxide as a key factor in the generation of inflammatory response and brake the main neurotransmitter in the gut in the pathogenesis of the small intestine motor disorders during endotoxemia. Also discusses anti-inflammatory cholinergic path, which is realized with the participation of the autonomic nervous system. Possible mechanisms by which tributyrinte as a component of nutritional support creates a multiplier effect in arresting the inflammatory response and normalization of intestinal motility are suggested. PMID- 27192854 TI - [MIKAMINOM ANTIFUNGAL THERAPY IN NEWBORNS AND INFANTS WITH SURGICAL PATHOLOGY]. AB - Prolonged empiric and etiotropic therapy of multidrug-resistant or pan-resistant bacterial flora in different gestation age newborns has led to the growth of resistant fungalflora in intencive care units (ICU). According to risk factors and rating scales every child of ICU undergoing the abdominal cavity surgery is threatened the development of a fungal infection and requires antifungal therapy appointment or causal prophylactic. In recent years, before the advent of medications of the group of echinocandins, therapy of invasive fungal infections has been a challenge. Currently alternative drug to diflucane in neonates and infants is micafungine (mycamine) in the dose of 2-8 mg/kg/day, depending on the signs of infestation and severity of the condition. PMID- 27192856 TI - [ANESTHESIA DURING THE SEPARATION OF THE FETUS IN FETU IN A 2 DAYS-LIFE CHILD WITH ACCOMPANYING NON-CORRECTED CRITICAL CONGENITAL HEART DISEASE (CHD)]. AB - The article describes a clinical case of treating a few- hours-life child with birth body weight--2900 g, length--50 cm, who had been extremely rare complex congenital malformations: fetus in fetu in the epigastrium with satisfactorily formed the lower half of the body of the failed twin, omphalocele and severe CHD. The surgical treatment was in terms of multicomponent endotracheal anesthesia. At the end of surgery puncture and catheterization of the epidural space at the level of L1/L2 holding the catheter up to Th9/Th10 for postoperative analgesia was made. Cardiotonic therapy and mechanical ventilation was performed after the operation. There have been signs of high pulmonary hypertension. On the 6th day of life the child was transferred to the Department of cardiac surgery and intensive care for the correction of complex combined CHD. At the age of 8 days of life performed the operation. Clamping of the aorta lasted for 21 minutes. On the 24th day of life has been deteriorating due to increasing renal failure and development of multiorgan failure, disseminated intravascular coagulation syndrome. After repeated resuscitations the child died at the age of 25 days of life. PMID- 27192858 TI - [PECULIARITIES OF ANESTHESIA AND MECHANICAL VENTILATION IN CHILDREN WITH SURGICAL PATHOLOGY AND RELATED CONGENITAL HEART DEFECTS]. AB - Unfortunately, last years there are more and more children with multiple malformations. Often in the intensive care unit appears children with problems requiring urgent surgical intervention. Congenital heart diseases (CHD) are often accompanying pathology. There are specific changes in hemodynamics in this category of children, which influence parameters of mechanical ventilation, leading sometimes to extremely undesirable consequences. Accordingly, this review deals with the features of anesthesia for various surgical interventions in children with severe (often uncorrected) accompanying CHD. PMID- 27192857 TI - [THE USE OF 20% LIPOFUNDIN INFUSIONS AT THE APPEARANCE OF TOXIC PROPERTIES OF ROPIVACAINE 2 MG/ML IN CHILD 1.5 MONTHS AT THE POSTOPERATIVE PERIOD WITH EPIDURAL ANALGESIA]. AB - Introduction of local anesthetic proved application of epidural (EP) as an effective and safe way of an analgesia in intra- and the post-operational period and now it is widely applied at children of all age groups (1). However there is a number of contraindications for application of this type of an analgesia. At children till 6 months lower dosages of a ropivacain of 2 mg/kg are applied, considering their age features. At the phenomena of system toxicity infusion of 20% lipofundin is applied. The child has an age 1.5 months, weight 5230 g, with the diagnosis a cystous dysplasia of both kidneys, a megaureter at the left and on the right, lack offunction of the left kidney operation a laparoscopic nefrureterektomia is executed at the left. In the postoperative period at application of EP of an analgesia ofropivacain 2 mg/ml by a drop way introduction in a standard dosage of 0.2 mg/kg of body weight an hour the repeating episodes of convulsions which were regarded as manifestation of toxic properties of local anesthetic were noted. Infusion of 20% lipofundin of 15 ml (2.8 ml/kg of body weight) within 30 minutes with a positive effect was applied. EP an analgesia was recoloured. PMID- 27192859 TI - [THE DIAGNOSTIC AND THERAPEUTIC BRONCHOSCOPY IN CARDIAC PATIENTS UNDERGOING MECHANICAL VENTILATION IN THE POSTOPERATIVE PERIOD]. AB - The review presents an analysis of domestic and foreign literature on the use of bronchoscopy in patients with obstructive respiratory failure in the ICU. Separately considered the issue of additional research when performing bronchoscopy and create an algorithmfor the application of diagnostic and therapeutic bronchoscopy in cardiac surgical patients undergoing mechanical ventilation. PMID- 27192860 TI - [Diagnostics and intensive therapy of acute respiratory distress syndrome. FAR's clinical guidelines]. PMID- 27192861 TI - [HOLDING OBJECTIVE STRUCTURED CLINICAL EXAMINATIONS FOR ANESTHESIOLOGY AND INTENSIVE CARE CLINICAL RESIDENCY IN STATE GRADUATES CERTIFICATION]. AB - The modern system of medical education requires objective methods to assess clinical competence of medical specialists. Application of objective structured clinical examination (OSCE) during the final certification of graduates of clinical residency allows to evaluate the theoretical knowledge, manual skills. Enabling simulation scenarios in the program makes it possible to objectively evaluate the important non-technical skills of anesthesiologists, identify gaps in the system of training and modify it. The experience of the objective structured clinical examination as part of the state certification of graduates of clinical residency of the Department ofAnesthesiology and Intensive Care, Military MedicalAcademy after C M Kirov allows us to consider this technique in an objective way a comprehensive assessment of the competence of health professionals. Students confirmed its highly realistic, they have revealed the presence of emotional stress during the simulation sessions, the majority agreed that the simulation session increased the level of their readiness to address these situations in clinical practice. Staff of the department is planning to testing and introduction rating scales into a system of assessment, to improved exam program, increasing the number of clinical scenarios for simulation sessions. PMID- 27192862 TI - [The memory of Raisa Ivanovna Novikova]. PMID- 27192863 TI - [The memory of Aleksandr Iosifovich Saltanov]. PMID- 27192864 TI - [The memory of Stanislav Valerianovich Obolenskiy]. PMID- 27192865 TI - [Neuronal migration in the brain and the mechanisms controlling the migration]. PMID- 27192866 TI - [Foreword]. PMID- 27192867 TI - [Structural study of enzymes involved in heme metabolism]. PMID- 27192868 TI - [Free N-glycans (FNG)--occurrence and diverse mechanisms for their formation and degradation]. PMID- 27192869 TI - [Role of Nitric Oxide in Plant Defense System]. PMID- 27192870 TI - [Optogenetics on non-excitable cells]. PMID- 27192871 TI - [Astrocytes connect synapses with blood vessels]. PMID- 27192872 TI - [DDX5 is a novel targeting protein of tumor suppressor ARF]. PMID- 27192873 TI - [The mechanism of proteasome inhibition-mediated mitochondrial impairment]. PMID- 27192874 TI - [Functional properties of gamma-secretase in the yeast reconstitution system]. PMID- 27192875 TI - [Transcription factor Npas4 regulates the development of dendritic spines in newborn olfactory bulb interneurons depending on sensory experience]. PMID- 27192876 TI - [Transgenic mouse model for imaging of inflammation in vivo]. PMID- 27192877 TI - [Neuronal circuitry for sensory processing in the spinal dorsal horn]. PMID- 27192878 TI - [Clarifying the novel myeloid differentiation mechanisms through identifying PU.1 target genes]. PMID- 27192879 TI - [Roles of TRPA1 in painful peripheral neuropathy]. PMID- 27192881 TI - [Regulation of mRNA length by FUS]. PMID- 27192880 TI - [Novel lysophospholipase D-type enzymes involved in the biosynthesis of N acylethanolamines and lysophosphatidic acids]. PMID- 27192882 TI - [Molecular mechanisms of LRRK2-mediated abnormal phosphorylation of Tau protein]. PMID- 27192883 TI - [The ribosome cycle and translational regulation by the formation of 100S ribosome]. PMID- 27192884 TI - [Mannose trimming mechanism in endoplasmic reticulum-associated degradation of glycoproteins]. PMID- 27192885 TI - [Development of a method for identifying the substrates of specific ubiquitin ligases]. PMID- 27192886 TI - [A novel flow cytometry-based cell capture platform for the detection, capture and molecular characterization of rare tumor cells in blood]. PMID- 27192888 TI - CLINICAL FEATURES AND GENETIC ANALYSIS OF SIX PATIENTS WITH WISKOTT-ALDRICH SYNDROME REPORTING TWO NOVEL MUTATIONS: EXPERIENCE OF ERCIYES UNIVERSITY, KAYSERI, TURKEY. AB - AIM: The Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency characterized by micro-thrombocytopenia, eczema, and recurrent infections. We aimed to share our experience with six children with WAS, including two patients with two novel mutations. MATERIAL AND METHOD: We present phenotypical and laboratory description of six patients with WAS. The initial clinical presentation, biochemical and radiological features, molecular diagnosis together with long-term follow-up data are provided. RESULTS: The patients showed increased serum levels of IgE; otherwise the serum levels of IgM were decreased. The percentages of CD3+ T cells were decreased or within lower limit. Four patients underwent molecular genetics analysis and Western blot studies; two of them showed unpublished mutations: a hemizygous splice site mutation in intron 8 (c.778-2A>T), and a hemizygous deletion in exon10 of the WASP gene (c.1017delT; p.S339fsX444) were detected. Western blot studies confirmed the reduced WAS protein expression in peripheral mononuclear blood cells in four studied patients. CONCLUSIONS: The major characteristics of patients were thrombocytopenia with decreased mean platelet volume and bleeding. All patients had been previously misdiagnosed as idiopathic thrombocytopenic purpura, demonstrating the importance of a careful differential diagnosis, and intense evaluation. PMID- 27192887 TI - A FURTHER PATIENT OF PURE 15q DELETION: CLINICAL AND MOLECULAR CYTOGENETIC FINDINGS. AB - A deletion of the distal long arm of chromosome 15 is generally reported with the formation of ring chromosome 15, whereas an isolated 15q deletion is rarely described. Here we report an 11 year-old girl, from non-consanguineous parents, who was referred to the Pediatric Genetics Department with growth retardation and multiple congenital abnormalities. In her medical history, she had a cleft palate, hip dislocation and crossed renal ectopia. Dysmorphological evaluation revealed a triangular face, low-set ears, fissured cleft tongue, micrognathia, proximally placed hypoplastic thumbs, genu valgus, 2-3 toe skin syndactyly, clinodactyly and nail hypoplasia. Speech problems were also noticed. The karyotype was normal. Subtelomeric fluorescent in-situ hybridisation (FISH) analysis showed a de novo terminal deletion about 755 kb. Furthermore, the breakpoint was located within the CHSY1 gene that is responsible for Temtamy preaxial brachydactyly syndrome which shares clinical features with 15qter deletion syndrome. To the best of our knowledge, this deletion is the smallest among reported patients. It is considered that the patient presented here significant contribution to phenotype-genotype correlation in 15q deletion patients. PMID- 27192889 TI - CO-OCCURRENCE OF PRIMARY MICROCEPHALY CAUSED BY A NOVEL HOMOZYGOUS ASPM MUTATION ALONG WITH X-LINKED ICHTHYOSIS IN THE SAME PATIENT. AB - Autosomal recessive primary microcephaly is a heterogeneous genetic disorder caused by genes that affect neurogenesis. This form of microcephaly has not been associated with other congenital anomalies. ASPM mutations have been identified as the major cause implicated in autosomal recessive primary microcephaly. X linked recessive ichthyosis, is an inborn error of steroid sulfatase metabolism characterized by dark and adhesive scaly skin. Here, we examined an Egyptian boy presenting with microcephaly and simplified gyral pattern. Additionally, he had ichthyosis that goes with the X-linked type. Mutation analyses of the ASPM gene for autosomal recessive primary microcephaly and STS gene of X-linked recessive ichthyosis were conducted revealing a co-occurrence of a novel homozygous splice site mutation of ASPM gene (c.2936+1G>A) and a partial deletion of STS spanning from exon 7-10. We propose that the phenotype of our patient results from the combined effects of mutations in both ASPM and STS that account for the neurological signs and skin manifestations, respectively. The association of isolated X-linked recessive ichthyosis and autosomal recessive primary microcephaly has never been reported in the literature. Careful clinical and genetic assessment of patients with atypical clinical phenotypes is crucial for detecting such rare double mutations and thus proper genetic counseling. PMID- 27192890 TI - PARTIAL TRISOMY 4p AND PARTIAL MONOSOMY 13q: CASE REPORT AND A LITERATURE REVIEW. AB - We report on a term first born dichorionic-diamniotic twin with deletion of the distal long arm of chromosome 13, partial trisomy of the short arm of chromosome 4, intrauterine growth retardation, and multiple anomalies including microcephaly, colpocephaly, absent corpus callosum, bulbous tip of the nose, large and low set ears, macroglossia, thin upper lip, double outlet right ventricle, atria/ventricular septal defect, cleft mitral valve, pulmonary stenosis, single umbilical artery, multicystic dysplastic left kidney, sacral dimple, anterior displacement of anus, simian creases, abnormal thumb (congenital clasped thumb), overlapping toes, and congenital hypothyroidism. This is the first report of a patient with partial trisomy 4p and partial monosomy 13q. PMID- 27192891 TI - 22.5 MB DELETION OF 13q31.1-q34 ASSOCIATED WITH HPE, DWM, AND HSCR: A CASE REPORT AND REDEFINING THE SMALLEST DELETED REGIONS. AB - Partial deletion of the long arm of the chromosome 13, 13q deletion syndrome is a rare chromosomal disorder characterized by severe growth and mental retardation, microcephaly, facial dysmorphism, brain malformations (holoprosencephaly, Dandy Walker malformation), distal limb defects, eye anomalies, genitourinary and gastrointestinal tract malformations (Hirschsprung's disease). Approximately 1.2 Mb region in 13q32 was suggested as minimal critical region which is responsible for severe mental and growth retardation and brain anomalies. Here we described a male patient with de novo interstitial deletion of 13q31.1-q34 associated with short stature, microcephaly, facial dysmorphism, clinodactyly, cryptorchidism, micropenis, epilepsy, HPE, DWM, and HSCR. According to the literature review, present case indicated that smallest deleted region associated with DWM and HPE might be located at the 13q32.3, limb defects 13q34, anogenital malformations 13q33.3-34, and HSCR 13q31.1-32.1. PMID- 27192892 TI - A MOLECULARLY CHARACTERIZED INTERSTITIAL DELETION ENCOMPASSING THE 11q14.1-q23.3 REGION IN A CASE WITH MULTIPLE CONGENITAL ABNORMALITIES. AB - Interstitial deletion of chromosome 11 long arm is a rare event. In most of the interstitial deletions on the long arm of chromosome 11 both the position and the size of these deletions are heterogeneous making a precise karyotype-phenotype correlation. In only a few of the reported cases has the deletion been molecularly characterized. Our patient was a 13-year-old male presented; mental motor retardation, strabismus, myopia, retinopathy, sensorineural hearing loss, a long and triangular face, a broad forehead, hypotelorism, nasal septal deviation, a beaked nose, hypoplastic ala nasie, bilateral low-set ears, a high arched palate, crowded teeth, retrognathia, thin lips, a long neck, and sloping shoulders, hyperactive behavior, pulmonary stenosis and lumbar scoliosis. Conventional cytogenetic analysis revealed 46,XY,del(11)(q14.1-q23.3) karyotype in the patient. Array-CGH analysis of the patient's DNA revealed an interstitial deletion encompassing 33.2 Mb in the 11q14.1-q23.3 genomic region (chr11: 83,161,443-116,401,751 ; Hg19). In this report, we present a patient with an interstitial deletion on the long arm of chromosome 11 that encompassed the 11q14.1-q23.3 region; and, using array-CGH analysis, we molecularly characterized the deleted region. PMID- 27192893 TI - PARTIAL OCULOCUTANEOUS ALBINISM AND IMMUNODEFICIENCY SYNDROMES: TEN YEARS EXPERIENCE FROM A SINGLE CENTER IN TURKEY. AB - BACKGROUND AND AIM: Partial oculocutaneous albinism and immunodeficiency (OCA-ID) diseases are autosomal recessive syndromes characterized by partial hypopigmentation and recurrent infections. Moreover, some OCA-ID syndromes confer susceptibility to develop a life-threatening hyperinflammatory condition called hemophagocytic lymphohistiocytosis (HLH). We investigated the genetic, clinical and immunological characteristics of 20 OCA patients. MATERIAL AND METHODS: Herein, we present the clinical and immunological characteristics of 20 OCA patients who referred to the Department of Pediatric Immunology, Erciyes University Medical Faculty in Kayseri, Turkey between 2004 and 2014. RESULTS: Of the 20 OCA patients, 7 fulfilled diagnostic criteria for HLH, 9 showed defective functions of CD8 T cells and natural killer cells, and 8 received a definitive molecular diagnosis. Among the patients, we also report a patient diagnosed with two different genetic defects, in TYR and JAK3 genes, causing, respectively, OCA and ID. CONCLUSION: Our results illustrate the variability of clinical presentations and disease severity in OCA-ID patients, with consequent challenges in diagnosing and treating these patients. PMID- 27192894 TI - OCULOECTODERMAL SYNDROME: A NEW CASE WITH GIANT CELL GRANULOMAS AND NON-OSSIFYING FIBROMAS. AB - Oculoectodermal syndrome (OES) is a very rare disorder with an unknown etiology and characterized by aplasia cutis congenita, epibulbar dermoid and hyperpigmentation areas on the skin. To the best of our knowledge, two cases of OES have been reported to date with recurrent giant cell granuloma in the jaw and one of them also had a non-ossified fibroma in the long bones. Herein, we report the second case with aplasia cutis congenita, epibulbar dermoid, hyperpigmentation along Blaschko lines and also giant cell granuloma in the jaw and non-ossified fibromas in the bones. PMID- 27192895 TI - HYPOPHOSPHATASIA WITH THE ASSOCIATION OF INV(1)(q11,q21.3) AND CLEFT PALATE. PMID- 27192896 TI - AXILLARY ARTERY THROMBOSIS IN A NEWBORN HOMOZYGOUS FOR METHYLENETETRAHYDROFOLATE REDUCTASE (A1298C) MUTATION AND HETEROZYGOUS FOR FACTOR V LEIDEN (G506A) MUTATION. PMID- 27192897 TI - Y-CHROMOSOME DE NOVO RECOMBINANTS. IMPLICATIONS FOR NOMENCLATURE. PMID- 27192898 TI - A RARE COMBINATION OF 45,X/46,XY MOSAICISM AND Y CHROMOSOME MICRODELETION IN AN INFERTILE MAN WITH AZOOSPERMIA. PMID- 27192899 TI - [Diagnosis and treatment of solitary pterygoid benign lesions]. AB - OBJECTIVE: To investigate the clinical and pathological features of solitary pterygoid benign lesions, as well as the treatment and outcome of endoscopic surgery. METHOD: We retrospectively analyzed clinical data of 4 patients with pterygoid benign lesions in our department. High resolution CT and enhanced MRI were performed before the operations, then endoscopic surgeries were carried out under the circumstance of general anesthesia. After a follow-up in 12 months to 48 months, nasal endoscopy and MRI examination were performed. Therefore we are able to understand the situation of operations and postoperative recurrences, and to inquire about the changes of symptoms and the relief of symptoms before and after surgery. RESULT: From the Pathological diagnosis, it showed 2 cases of cystic lesions, 1 case of spindle cell lipoma, 1 case of inflammatory lesion. Postoperative follow up showed scar formation, smooth surface, no recurrence, and no new symptom. Nasal obstruction is relieved after the surgery, and no changes in the sympotoms of headache were observed. CONCLUSION: The combination of high resolution CT with enhanced MRI isimportant for ascertaining the location, extent and nature of the pterygoid lesions. Endoscopic surgery is a minimally invasive, safe, and effective method for the treatment of solitary pterygoid benign lesions. PMID- 27192900 TI - [Expression and clinical significance of MICA in laryngeal carcinoma tissue and cells]. AB - OBJECTIVE: To investigate the mRNA and protein expression of MICA in laryngeal squamous cell carcinoma tissue and the Hep-2 cells. METHOD: Reverse transcriptase polymerase chain reaction (RT-PCR) and Western-blot were used to detect the expression of MICA mRNA and protein levels in the Hep-2 cells and laryngeal cancer tissues. RESULT: The MICA mRNA showed higher expression in Hep-2 cells by RT-PCR. Compared with the control, the mRNA expression of MICA was significantly enhanced in laryngeal cancer tissues (t = 11.878, P < 0.01). The intensity of MICA expression is not related to the clinical stage of cancer. MICA protein demonstrated higher level expression by Western blot. The intensity of MICA protein expression was decreased with increased clinical stage in laryngeal cancer tissues. CONCLUSION: The MICA mRNA showed stronger expression in Hep-2 cells and laryngeal cancer tissues. The intensity of its expression is not related to clinical stage of cancer. The MICA protein expression was strong in Hep-2 cells. The intensity of MICA protein expression was decreased with increased clinical stage in laryngeal cancer tissues. MICA may play an important role in laryngeal carcinoma process. PMID- 27192901 TI - [Remote fitting models analysis of hearing AIDS from primary hospitals: 45 case reports]. AB - OBJECTIVE: To study the feasibility and the generalizability of the Remote fitting models of hearing AIDS from primary hospitals. METHOD: we comparative analyzed the speech recognition scores and satisfaction of 45 cases with traditional hearing AID fitting and with a hearing aid remote test respectively. RESULT: 45 cases were analyzed in each group, including traditional hearing AID fitting model and remote test, and 35 recovered in traditional fitting model group, and the recovery rate was 77.8%; Remote fitting model rehabilitation 42 cases, recovery rate was 93.3%, the difference was statistically significant (P < 0.05). In 6 weekend wear hearing AIDS, traditional fitting model of speech recognition rate increased by 19.40% on average, the average distance fitting model speech recognition rate increases by 27.47%, the average distance fitting model than traditional fitting the speech recognition rate increased significantly more (8.07%). Effect of hearing aid international questionnaire results suggest: 45 cases using traditional model fitting hearing AIDS patients, 33 cases (73.3%) satisfaction, 12 cases (26.7%) patients after use. Remote and 45 cases of using hearing AIDS fitting model, satisfied with 40 cases (88.9%), 5 cases (11.1%) patients after use. CONCLUSION: the curative effect and the satisfaction of remote fitting models of hearing AIDS on hearing impairment are better than that in patients with traditional fitting models. Therefore it is more worthy of clinical application especially in basic level hospitals. PMID- 27192902 TI - [The value of lidocaine through different routes of administration in the treatment of tinnitus: a Meta-analysis]. AB - OBJECTIVE: To evaluate the clinical value of lidocain in the treatment of tinnitus through three routes of administration (intravenous, intratympanic and acupoint injection) by analyzing literatures. METHOD: Articles were collected through Hownet, Wanfang, VIP, Pubmed, SciVerse ScienceDirect, Springer and OVID, etc. The articles were strictly evaluated based on their quality. The Meta analysis was performed to evaluate the outcomes by RevMan 5. 2 software. RESULT: A total of 16 articles with 1203 patients were enrolled in the analysis. Their tinnitus history ranged from 7 hours to 20 years. Assessment methods include tinnitus loudness levels, severity scales and subjective feelings. None of articles refer to maintaining time, instead of "short-term", "short" and so on. A total of 133 cases received intravenous injection and the effective rate was 73.4% (98 cases). 50 cases and 332 cases received intratympanic and acupoint injection respectively and their effective rates were 74.0% and 87.7%, respectively. The effective rate ranged from 42.4% to 58.3% in control group. Meta-analysis results indicate that all three routes of lidocaine administrations are more effective than conventional methods (P < 0.05). CONCLUSION: Different routes of lidocaine administration have a good but short time effects on the tinnitus control. It can effectively reduce the time of tinnitus habituation as a complementary treatment. But its value still needs further evaluation. PMID- 27192903 TI - [Analysis of olfactory rehabilitation after endoscopic sinus surgery in patients with chronic sinusitis and nasal polyps]. AB - OBJECTIVE: To evaluate the influence of endoscopic sinus surgery on olfactory disorder caused by chronic sinusitis and nasal polyps, by testing the olfactory function of seventy-four patients before and after endoscopic sinus surgery,and evaluate the outcomes of olfactory dysfunction after endoscopic sinus surgery in patients with choinc rhinosinusitis and the related factors. METHOD: The olfactory function of the seventy-four patients with chronic sinusitis and nasal polyps were tested by the T&T olfactory testing method at pre-operation and four weeks,twelve weeks, twenty-four weeks of post-operation. Patients were divided into two groups, according to whether combined with allergic rhinitis. Data were achieved by the scores of endoscopic appearances of Kennedy, and CT staging system of Lund-Mackey. Parallel processing standard endoscopic operation and processing specification during peri operation period. Analysing the degree of olfactory rehabilitation in chronic sinusitis and nasal polyps with allergic rhinitis. RESULT: (1) Compared with the level of olfactory function, significant improvement was found at first month;however, the olfactory function level 4 weeks after operations was significantly statistically different with that 12 weeks and 24 weeks after operations; (2) Lund-Mackey sinus CT higher score is related to the worse degree of postoperative nasal olfactory rehabilitation (P < 0.05). (3) The higher scores of endoscopic appearances of Kennedy is related to the worse degree of postoperative nasal olfactory rehabilitation (P < 0.05). (4) Allergic rhinitis is one of the factors of olfactory rehabilitation in chronic rhinosinusitis with olfactory dysfunction olfactory rehabilitation, the olfactory rehabilitation of patients with allergic rhinitis is worse than that in the patients with no allergic rhinitis. (5) Course of disease is one of the factors of chronic rhinosinusitis with olfactory dysfunction olfactory rehabilitation. Longer the course of disease, worse the olfactory rehabilitation. (6) E osinophil count was related to olfactory rehabilitation in chronic rhinosinusitis with olfactory dysfunction olfactory rehabilitation. Higher Eosinophil count, worse the olfactory rehabilitation. CONCLUSION: FESS plays a positive role in the improvement of olfactory impairment in patients with CRS. It is important to protect the olfactory mucous during surgical removal of sinonasal lesions. The standard intraoperative procedure, treatment on allergic rhinitis and regular follow-up after operation are also very important. PMID- 27192904 TI - [Efficacy of combined modality therapy for intractable difficult-to-treat rhinosinusitis]. AB - OBJECTIVE: To investigate the clinical effects of the combined modality therapy for the patients with difficult-to-treat rhinosinusitis (DTRS). METHOD: The clinical data involving 42 patients with DTRS were analyzed retrospectively. All patients received revision endoscopic sinus surgery (ESS) and combined modality therapy systematically and individually. The clinical effects of all patients were observed 6- and 12-month following revision ESS. RESULT: Forty-two patients were followed up for 6 months, whereas 35 patients were followed for 12 months post operation. VAS scores of the patients significantly improved (P < 0.01) 6- and 12-month after revision ESS, but there was no statistic difference (P > 0.05) between 6- and 12-month post operation. Moreover, Lund-Kennedy scores by endoscopy significantly improved (P < 0.01) 6- and 12-month following ESS. Similarly, there was no statistic difference (P > 0.05) between 6- and 12-month postoperatively. Additionally, within 6 months follow-up, 16 of 42 patients (38.1%) were cured, 19 of 42 patients (45.2%) were improved, and 7 of 42 patients (16.7%) were ineffective. The total effective rate in all patients was 83.3% 6 months postoperatively. While within 12 months follow-up, 11 of 35 patients (31.4%) were cured, 15 of 35 patients (42.9%) were improved, and 9 of 35 patients (25.7%) were ineffective. Hence, the total effective rate in 35 patients was 74.3% after 12-month follow-up. There was no statistic difference (chi2 = 1.019, P > 0.05) between 6- and 12-month postoperatively. CONCLUSION: Appropriate revision ESS plus the combined modality therapy has been proven to be an effective method for the treatment of DTRS. The clinical effects in this study are significant and stable, and thus it is worthy of further clinical applications. PMID- 27192905 TI - [Distribution and drug sensitivity test of bacteria of patients on chronic rhinosinusitis with or without nasal polyps]. AB - OBJECTIVE: To study the distribution and drug sensitivity test of bacteria of patients on chronic rhinosinusitis with or without nasal polyps. METHOD: The purulent discharges were collected from sinus of 175 patients with chronic rhinosinusitis with or without nasal polyps during endoscopic sinus surgery. The results of germiculture and drug sensitivity test were analyzed. RESULT: From 175 specimens, 118 (67%) showed positive results in germiculture. Among them, 79 strains of gram positive bacteria and 39 strains of gram negative bacteria were detected. Staphylococcus epidermidis, Staphylococcus aureus and Staphylococcus haemolyticus were the most common pathogens in gram positive bacteria. The most common pathogens of gram negative bacteria were P. Aeruginosa, Enterobacter aerogenes, Enterobacter cloacae. The sensitive antibiotic on gram positive bacteria were amikacin, Daptomycin, Linezolid, vancomycin, teicoplanin, amoxicillin and clavulanate potassium, cefuroxime, respectively. The sensitive antibiotics on Gram negative bacteria were amikacin, Cefoperazone/sulbactam and imipenem, ceftazidime ceftazidime, aztreonam, levofloxacin, respectively. CONCLUSION: Bacterial infection was common happened in the sinus cavity of patients with chronic rhinosinusitis with or without nasal polyps. Gram positive bacteria were the main pathogenic bacteria and gram positive bacteria and gram negative bacteria have great differences in the sensitivity of antibiotics. For patients with chronic rhinosinusitis, the using of antibiotics should depend on the drug sensitivity test. PMID- 27192906 TI - [Value of thyroid imaging reporting and data system and shear wave elastography for diagnosis of thyroid microcarcinoma]. AB - OBJECTIVE: To investigate the value of each single and combined applications of ultrasound thyroid imaging reporting and data system (TI-RADS), ultrasonic shear wave elastography in the diagnosis of thyroid microcarcinoma (TMC). METHOD: 323 patients with thyroid tiny nodules confirmed by surgery and pathology were analyzed prospectively. Then their TI-RADS and shear wave elastography features were summarized. SWE elasticity indices (mean, minimum and maximum value of interest) of nodules were measured. The surgical pathology results were regarded as the gold standard to calculate the sensitivity, specificity, accuracy, positive predictive value and negative predictive value of TI-RADS, shear wave elastography and their combination in the diagnosis of TMC. The receiver operating characteristic (ROC) curve of TI-RADS, shear wave elastography and combined application of both were drawn. The area under the ROC curve were calculated. Furthermore, the value of combined application of both examinations in the diagnosis of thyroid microcarcinoma (TMC) was investigated. RESULT: From 323 nodules,253 were thyroid carcinomas and 70 were benign. Areas under the ROC curves (AUC) of SWE parameters were 0. 648,0. 629 and 0. 605. For SWE, the optimal cut-off value according to ROC curve was SWE_max = 65.50 kPa and SWE_mean = 37.50 kPa. Generally, the sensitivity, specificity, accuracy, PPV and NPV were 88.14%, 82.86%, 87.00%, 94.89% and 65.91% for TI-RADS, and 49.01%, 74.29%, 54.49%, 87.32% and 28. 73% for SWE. There were statistically significant differences in the sensitivity, accuracy, PPV and no statistically significant differences in the specificity, and NPV. The sensitivity,specificity, accuracy, PPV and NPV were 95.26%, 67.14%, 89.16%, 91.29% and 79.66% for combined application of both. The area under the ROC curve of TI-RADS, shear wave elastography and their combination were 0.763, 0.616, 0.804. For nodules <= 5 mm, the sensitivity, specificity, accuracy, PPV and NPV were 91.67%, 66.67%, 87.07%, 92.44% and 64.29%. However, for nodules 5-10 mm,the sensitivity,specificity, accuracy, PPV and NPV were 98.50%, 67.44%, 90.91%, 90.34% and 93.55%. CONCLUSION: The diagnose of TMC can be further improved by combined application of ultra sonic TI-RADS and SWE. PMID- 27192907 TI - [Expression and significance of p-Stat3 and its downstream gene c-myc in laryngeal squamous cell carcinoma tissue and cell line]. AB - OBJECTIVE: To detect the expressions of p-Stat3 and c-myc in human laryngeal squamous cell carcinoma (LSCC) tissue and Hep2 cell line, and to find the relationship between them. METHOD: Immunohistochemistry was used to detect the expressions of p-Stat3 and c-myc in 60 cases of LSCC and 30 cases of vocal cord polyp tissue. The protein levels of p-Stat3 and c-myc in Hep2 cell line was determined by immunocytochemistry. Western blotting was used to determine the protein levels of p-Stat3 and c-myc in Hep2 after treating with different concentrations of Stattic. RESULT: The positive rates of p-Stat3 and c-myc were 65% and 70% in the LSCC tissue, compared with that in the vocal cord polyp tissue, with significant difference (P < 0.05). The expression of p-Stat3 in LSCC tissue was associated with that of c-myc (r = 0.273, P < 0.05). The protein levels of p-Stat3 and c-myc were detected in the Hep2 cell line. Stattic inhibited Stat3 phosphorylation and c-myc in the Hep2 cell line in a concentration-dependent manner. CONCLUSION: p-Stat and c-myc were up regulated in the tissue of laryngeal squamous cell carcinoma and the Hep2 cell line. Stattic inhibits the constitutively active p-Stat3 signaling pathway, and downregulats the expression of c-myc. The strong constitutive p-Stat3 signaling pathway in LSCC makes p-Stat3 a target for the development of novel therapeutic strategies. PMID- 27192908 TI - [Analysis on the clinical outcomes of idiopathic sudden sensorineural hearing loss using the EuroQol 5-Dimension 3-Level questionnaire]. AB - OBJECTIVE: To investigate the applicability of EuroQol 5-Dimension 3-Level questionnaire (Chinese Version 1.0) (EQ-5D-3L) in the assessment of life quality of patients with idopathic sudden hearing loss. METHOD: In this retrospect study, the EQ-5D-3L was assigned to 60 patients with idopathic sudden hearing loss before and after drug therapy. Audiometry examinations were undertaken and concomitant symptoms were recorded. A Wilcoxon rank sum test was applicated to the comparisons of results of EQ-5D-3L before and after the treatment, a t-test for results of EQ-VAS and a Kappa measurement for the consistency of certain dimension correlated with the symptoms. RESULT: Sixty patients completed the five questions and visual analog scale of the EQ-5D. A statistically significant changes of pain/discomfort, anxiety/depression before and after the treatment were observed (P < 0.05). The domains of mobility, self-care and usual activities did not show statistically significant different (P > 0.05). The dimension of pain/discomfort was in agreement with the concomitant symptoms. And the result of EQ-VAS was in agreement with the therapeutic outcome. CONCLUSION: It is suitable for the EQ-5D to be a general health measure with sensitivity to clinical change in idiopathic sudden sensorineural hearing loss, which monitors the patients' outcomes. PMID- 27192909 TI - [Construction and screening effective sequence of shRNA targeting human trefoil factor 3]. AB - OBJECTIVE: Trefoil factor 3 plays a pivot role in oncogenic transformation, growth and metastatic extension of solid tumours besides mucosal protection. We screened the best siRNA sequence targeting human TFF3 by the transient transfection of the lentiviral mediated shRNA into thyroid carcinoma K1 cells which secrete TFF3 themselves. METHOD: Four siRNA transcription template hairpin structure target potential sites in human TFF3 mRNA sequence(132,170,258 and 537 bp,seperately) were selected and synthesized,as well as one negative shRNA(shRNAC). After annealing in vitro, insert pLVX-shRNA-puro construct recombinant plasmid, then enzyme digestion and sequencing analysis. The lentiviral-shRNAs were transient-transfected into K1 cells. TFF3 mRNA and protein levels were test by real-time PCR and western blot respectively in K1 cells at 48h post transient-transfected. RESULT: Genetic mutations in two sequences of shRNA1~2, so the follow-up study terminated. The TFF3 expression were obviously inhibited in K1 cells at 48 hours post transient-transfected of shRNA3 and shRNA4. TFF3 (258-276) showed the highest silencing efficiency (TFF3 mRNA reduced 60.67% and TFF3 protein reduced 56.44%, P < 0.01) when the transfection efficiency was 76.83%. CONCLUSION: pLVX-shRNA-puro-TFF3 expression plamid were successfully constructed and the highest efficiency sequences were screened. All these laid a foundation for further study about the function of TFF3 gene. PMID- 27192910 TI - [The evaluation of curative effect of radiofrequency thermocoagulation on semilunar ganglion of aged patients with recurrent trigeminal neuralgia]. AB - OBJECTIVE: To investigate curative effect and importance of radiofrequency thermocoagulation onsemilunar ganglion of aged patients with recurrent trigeminal neuralgia. METHOD: 112 cases with recurrent trigeminal neuralgia were performed with radiofrequency thermocoagulation on semilunar ganglion by puncture through skin under local anesthesia. RESULT: The maintaining effective duration in 112 cases was 7.3 +/- 1.3 years after primary therapy. After the first thermocoagulation, 89.28% (100/112) patients got the relief from pain immediately, 8 (7.14%) cases also recieved the same effect after twice treatment. However two cases (2.6%) had no effects. The total effective rate was 98.21%. During five follow-up years, VAS scores, dose of carbamazepine and satisfaction were better than those before the treatment. The effective rate was still over 57.5% within three years after the treatment. The recurrent risk increased obviously from 40 months after the treatment by Kaplan-Meier method. CONCLUSION: Semilunar ganglion of radiofrequency thermocoagulation was an ideal option for old-age patients with trigeminal neuralgia. It can be performed repeatedly. PMID- 27192911 TI - [The significance of keratinocyte in hyperproliferation of middle ear cholesteatoma]. AB - OBJECTIVE: In order to investigate the interaction between the cytokines and keratinocyte and determine the role of cytokines in hyperproliferative of chronic otitis media with cholesteatoma, we observe the expression of matrix metalloproteinase 9 (MMP9), vascular endothelial growth factor (VEGF), keratinocyte growth factor (KGF) and its receptor (KGFR) in middle ear cholesteatoma. METHOD: We examined the expression of MMP9, VEGF, KGF, KGFR and Ki 67 by immunohistochemistry in 50 specimens from chronic otitis media with cholesteatoma and 15 specimens from the normal skin of external auditory meatus. Ki-67 as an evaluation of cholesteatoma proliferation markers were used to detect the keratinocyte proliferative activity. RESULT: (1) The expression of VEGF and MMP9 in cholesteatoma specimens was higher than normal skin, and the difference was statistically significant (t = 4.914, P < 0.01; t = 3.284, P < 0.01). (2) The expression of KGF and KGFR in middle ear tissues was higher than normal skin, and the difference was statistically significant (t = 4.814, P < 0.01; t = 3.104, P < 0.01); The expression of KGF and KGFR increased, and the expression of Ki-67 also correspondly increased in the cholesteatoma. (3) In the tissue MMP9 and VEGF were positive. Mean optical density increased as well. KGF expression also increased accordingly. CONCLUSION: MMP9, VEGF, KGF and KGFR proteins played an important role in hyperproliferation of cholesteatoma tissues. VEGF, MMP9 and KGF had a synergistic effect in hyperproliferation of cholesteatoma tissues. PMID- 27192912 TI - [Value of high-resolution CT reconstruction technique in the assessment of patients with hearing problem after the ossicular chain reconstruction]. PMID- 27192913 TI - [Correlations between allergen skin prick tests and patients' symptoms and quality of life]. PMID- 27192914 TI - [The observation of therapeutic effect of auricle keloid by the operation of through resection]. PMID- 27192915 TI - [Analysis of 20 mutation sites in 4 genes in neonates in Shaoguan City]. PMID- 27192916 TI - [A case of vocal cord contact granuloma after vocal cord polyp surgery]. AB - The vocal cord polyp is easy to relapse after surgery, but if the patient has recurrence in a short term, it is necessary to consider it as postoperative vocal cord contact granuloma. If the patients with contact granuloma after surgical treatment had severe impact on the pronunciation, it is necessary to be operated and confirmed by pathology and given the treatment of acid suppression, in order to avoid postoperative recurrence. PMID- 27192917 TI - [A case of large solitary fibrous tumor originated from the neck]. AB - Solitary fibrous tumor (SFT) is a rare spindle cell neoplasm that usually develops in the pleura and peritoneum. The head and the neck region is involved in only 6% of the cases. We described a rare case of large SFT originated from the right neck region in a 32-year-old man. Enhanced CT scan revealed two large completely resected masses in the carotid sheath region and the right thyroid gland. Immunohistochemical studies showed positive CD34, CD99, NSE and bcl-2, and negative Desmin, NF, S-100, CD31, F8, CK, MBP, indicating that the tumor was benign. It showed no evidence of recurrence on the patient during 9 years follow up. PMID- 27192918 TI - [Maxillary sinus carcinoma combined with maxillary sinus fungal sinusitis: one case report]. AB - A 70 years old male patient complained a sense of swelling on right facial, mild pain, and the obstruction of right nasal, no complain of facial numbness and toothache. Physical examination showed the slight bulging on right facial with mild tenderness, purulent nasal secretions on the right middle nasal meatus, and no significant neoplasm. CT scan showed that soft density tissue in the right maxillary sinus,and the high density tissue in some period. Postoperative diagnosis: carcinoma of maxillary sinus with fungal sinusitis. PMID- 27192919 TI - [One case report of nasal sinus ossification]. AB - A 8-years-old male patient with a bulge of left eye ball for one mongth was hospitalized. The inspection of the patient showed the movement on the left side of the lateral nasal wall and a narrow nasal cavity. Orbital CT showed that the left orbital ethmoid sinus, maxillary sinus cyst, left orbital, sphenoid sinus, nasal cavity were damaged. A resection with the combination of approaches including the left maxillary sinus, the ethmoid sinus, and the sphenoid sinus osteofibroma was performed. 5 days after the operation, the nasal packing material was removed and 7 days after the operation the stiches were removed. The recovery of the patient was satisfied after the operation and no recurrence was observed during one and half years follow up. PMID- 27192920 TI - [The diagnosis and treatment of one huge cystic lymphangioma in etropharyngeal space]. AB - One child was hospitalized because of repeated cough and sputum. The biopsy diagnosis in local hospital was cystic lymphangioma in retropharyngeal space. We carried out transoral incision and drainage by catheter under general anesthesia. Put into the surgical cavity a suction drainage tube, and injected 5 mg dexamethasone and 8mg Bleomycin. He had nasogastric liquid diet after operation. We removed the suction drainage tube two weeks later. No recurrence was found following up over two years. PMID- 27192921 TI - [Progress of Th17 cells in chronic rhinosinusitis]. AB - Chronic rhinosinusitis is a common disease and frequently encountered disease in otolaryngology, but the therapeutic effect is not ideal. While its pathogenesis is exploring in the continuously. Found in the recent years, Th17 cells are a new subset of T cells and closely related with inflammatory disorders, autoimmune diseases and cancer. Its differentiation, regulation and biological effects are widely noted as a hot area of research. This review explores the discovery of differentiation and regulation of Th17 cells, the relationship between related cytokines and chronic rhinosinusitis, in order to have a beteer knowledge of chronic rhinosinusitis. This review regards Th17 cells as the main clue, nevertheless, lacking consideration of the impacts of other factors on chronic rhinosinusitis. PMID- 27192922 TI - [Treatment options of T1 glottic carcinoma]. AB - T1 glottic carcinoma is part of early laryngeal carcinoma which involves the vocal cords, including anterior commissure or posterior commissure. We analyzed the treatment options of T1 glottic carcinoma by reviewing the related literatures about T1 glottic carcinoma treated by conservative surgery (open surgery and laser microsurgery), radiotherapy, robot surgery, photodynamic treatment. PMID- 27192923 TI - [Development of improving speech perception of cochlear implants in noisy environment]. AB - Cochlear implantation has been a standard therapy for treating severe deafness because patients who receive it have better speech perception. However, the hearing performance of cochlear implantation in noisy environment is far from satisfaction. Efforts have been made to reverse such condition, such as EAS, bimodal stimulation, environment-adaptive speech enhancement and multipolar stimulation, and patients who receive it get more or less better speech perception in noisy environment than traditional cochlear implantation. PMID- 27192924 TI - Kinematic analysis of the drag flick in field hockey. AB - Attaining high speed of the stick head and consequently of the ball is essential for successful performance of the drag flick in field hockey, but the coordination pattern used to maximise stick head speed is unknown. The kinematics of the drag flick was studied in ten elite hockey players who performed twenty shots each towards a target located 1.5 m high. A 150 Hz active marker motion analysis system was used, alongside two force plates to detect foot touchdown. Angular velocity and contribution to stick endpoint speed of upper body joints were analysed. Repeated measures ANOVA was used to compare timing of onset and peak angular velocities between joints. Participants used a kinematic pattern that was close to a proximal-to-distal sequence. Trunk axial rotation and lateral rotation towards the target, right wrist flexion and left wrist extension were the main contributors to stick endpoint speed. Coaches should emphasise trunk rotations and wrist flexion and extension movements for maximising stick head speed. Given the high level of the participants in this study, the coordination of joints motions, as reported here, can serve as a guideline for drag flick training. PMID- 27192926 TI - Late radio-lunate arthritis following ulnar shortening osteotomy. PMID- 27192925 TI - Use of a DNA film on a self-assembled monolayer for investigating the physical process of DNA damage induced by core electron ionization. AB - PURPOSE: A novel two-layer sample composed of a deoxyribonucleic acid (DNA) film and self-assembled monolayer (SAM) was prepared on an inorganic surface to mimic the processes in which DNA is damaged by soft X-ray irradiation. MATERIALS AND METHODS: A mercaptopropyltrimethoxysilane (MPTS) SAM was formed on a sapphire surface, then oligonucleotide (OGN) molecules were adsorbed on the MPTS-SAM. The thicknesses and chemical states of the layers were determined by X-ray photoelectron spectroscopy (XPS) and near-edge X-ray fine structure (NEXAFS) around the phosphorus (P) and sulfur (S) K-edges. To induce the damage to the OGN molecules, the sample was irradiated with synchrotron soft X-rays. The chemical state of the OGN molecules before and after irradiation was examined by NEXAFS around the nitrogen (N) K-edge region. RESULTS: The thickness of the MPTS-OGN layer was approximately 7.7 nm. The S atom of the OGN molecules was located at the bottom of the OGN layer. The peak shape of the N K-edge NEXAFS spectra of the MPTS-OGN layers clearly changed following irradiation. CONCLUSIONS: The MPTS-OGN layer formed on the sapphire surface. The chemical states and the structure of the interface were elucidated using synchrotron soft X-rays. The OGN molecules adsorbed on the MPTS films decomposed upon exposure to soft X-ray irradiation. PMID- 27192929 TI - Obituary. PMID- 27192927 TI - Treatment of post-traumatic chronic osteomyelitis of lower limbs by bone transport technique using mono-lateral external fixator: Follow-up study of 18 cases. AB - PURPOSE: To review the results of the treatment of post-traumatic chronic osteomyelitis of lower limbs by bone transport technique using mono-lateral external fixator. PATIENTS AND METHODS: A total of 18 patients with post traumatic chronic osteomyelitis of lower limbs were treated by bone transport technique using mono-lateral external fixator in this study. Seven cases (patients No. 1-7) were performed early BGPO (autologous ilium bone grafting and plate osteosynthesis) intervention after BT (bone transport). The end results were assessed by the criteria of ASAMI and Paley et al. Some data between the cases with and without the intervention of early BGPO were subjected to statistical analysis of Student's t-test. RESULTS: The overall average time for union was 10.8 months. The average union time of the non-early BGPO cases was 52.27 +/- 7.82 weeks while the early BGPO cases took a shorter time of 36.86 +/- 5.34 weeks (P < 0.001). The overall average duration from bone transport to removal of external fixator was 10.0 months. The average duration from bone transport to removal of external fixator in the non-early BGPO cases was 51.55 +/ 7.45 weeks while the early BGPO cases took a shorter time of 29.29 +/- 5.47 weeks (P < 0.001). The overall average of BHI was 1.77 months cm(-1). The average of BHI in the non-early BGPO cases was 2.25 +/- 0.25 months cm(-1) and the average BHI of the early BGPO cases was 1.22 +/- 0.114 months cm(-1) (P < 0.001). There were 31 additional surgeries and 38 complications in total after bone transport treatment. The bone results were excellent in 15 cases, good in 3 cases. The functional results were excellent in 9 cases, good in 6 cases and fair in 3 cases. CONCLUSIONS: 1. Bone transport technique using mono-lateral external fixator is an effective method for the treatment of post-traumatic chronic osteomyelitis. 2. Early BGPO intervention after bone transport is a feasible method to shorten the external fixation time and the total duration of treatment. PMID- 27192930 TI - New Insights into the Molecular Dynamics of P3HT:PCBM Bulk Heterojunction: A Time of-Flight Quasi-Elastic Neutron Scattering Study. AB - The molecular dynamics of organic semiconductor blend layers are likely to affect the optoelectronic properties and the performance of devices such as solar cells. We study the dynamics (5-50 ps) of the poly(3-hexylthiophene) (P3HT): phenyl-C61 butyric acid methyl ester (PCBM) blend by time-of-flight quasi-elastic neutron scattering, at temperatures in the range 250-360 K, thus spanning the glass transition temperature region of the polymer and the operation temperature of an OPV device. The behavior of the QENS signal provides evidence for the vitrification of P3HT upon blending, especially above the glass transition temperature, and the plasticization of PCBM by P3HT, both dynamics occurring on the picosecond time scale. PMID- 27192928 TI - Assessment of different methods to estimate bovine colostrum quality on farm. AB - AIMS: To evaluate two different hydrometers and an optical and a digital Brix refractometer for the assessment of bovine colostrum quality, in terms of accuracy and precision compared with the measurement of IgG concentrations using radial immunodiffusion (RID), and to evaluate the reliability and repeatability of the Brix refractometers. METHODS: To determine reliability and repeatability, 145 colostrum samples were tested by two independent observers twice, using the optical and digital Brix refractometers. A further 193 colostrum samples from Holstein cows were collected on one commercial dairy farm at first milking and tested with two hydrometers and an optical and digital Brix refractometer. An aliquot of each sample was frozen for RID measurement of IgG concentrations and samples were classified as poor (<=50 g IgG/L) or good (>50 g IgG/L) quality colostrum. Intraclass correlation coefficients (ICC) were used to determine inter and intra-observer reliability and repeatability. Optimised cut-off values for the four devices were determined using receiver operating characteristics (ROC) analysis with the RID results as the reference. Using these cut-offs, sensitivities and specificities for determining good quality colostrum were calculated. RESULTS: The ICC for inter-observer reliability was 0.98 for the optical Brix refractometer, and for intra-observer repeatability was 0.97 and 0.98 for the optical and the digital Brix refractometers, respectively. For the 193 colostrum samples, 67 (34.7%) had concentrations of IgG <=50 g/L determined by RID. Optimised cut-off values evaluated by ROC analysis were higher for all devices compared with manufacturer reference or previously published values. Using these values, the sensitivities for the two hydrometers, and the optical and the digital Brix refractometers were 0.73, 0.71, 0.56 and 0.79, respectively; specificities were 0.72, 0.61, 0.90 and 0.69, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The Brix refractometers provided the most accurate assessment of colostrum quality of the devices evaluated, and demonstrated excellent precision in terms of repeatability. To provide optimal health for newborn calves, a sufficient intake of good quality colostrum is essential. The Brix refractometers provide rapid, convenient tools for classification of colostrum quality. PMID- 27192931 TI - Consensus Among International Ethical Guidelines for the Provision of Videoconferencing-Based Mental Health Treatments. AB - BACKGROUND: Online technologies may reduce barriers to evidence-based mental health care, yet they also create numerous ethical challenges. Recently, numerous professional organizations and expert groups have produced best-practice guidelines to assist mental health professionals in delivering online interventions in an ethically and clinically sound manner. However, there has been little critical examination of these international best-practice guidelines regarding appropriate electronic mental health (e-mental health) service delivery via technologies such as videoconferencing (including Skype), particularly for specific, vulnerable populations. Further, the extent to which concordance exists between these guidelines remains unclear. Synthesizing this literature to provide clear guidance to both mental health professionals and researchers is critical to ensure continued progress in the field of e-mental health. OBJECTIVE: This study aims to review all currently available ethical and best-practice guidelines relating to videoconferencing-delivered mental health treatments in order to ascertain the recommendations for which international consensus could be found. Additionally, this review examines the extent to which each set of guidance addresses several key special populations, including children and young people, and populations living with illness. METHODS: This systematic review examined guidelines using a two-armed search strategy, examining (1) professional organizations' published guidance; and (2) MEDLINE, PsycINFO, and EMBASE for the past ten years. In order to determine consensus for best-practice, a recommendation was considered "firm" if 50% or more of the reviewed guidelines endorsed it and "tentative" if recommended by fewer guidelines than these. The professional guidelines were also scored by two raters using the Appraisal of Guidelines for Research and Evaluation II (AGREE-II) criteria. RESULTS: In the study, 19 guidelines were included, yielding 11 specific "firm" and a further 123 "tentative-level" recommendations regarding the appropriateness of e-mental health, competence, legal and regulatory issues, confidentiality, consent, professional boundaries, and crisis management. International consensus yielded firm guidance across almost all areas except professional boundaries and some aspects of determining the appropriateness of e-mental health. Few guidelines specifically addressed special populations. Overall guideline quality varied; however, 42% (8/19) of the guidelines scored at least 5 out of 7. CONCLUSIONS: This synthesis of guidelines provides a foundation for clinicians and researchers utilizing e-mental health worldwide. The lack of specific guidance relating to special populations is an area warranting further attention in order to strengthen mental health professionals' and researchers' capacity to ethically and effectively tailor e-mental health interventions to these groups. PMID- 27192933 TI - Erythema papulosa semicircularis recidivans associated with primary pancreas B cell lymphoma. PMID- 27192934 TI - Altered hippocampal function in major depression despite intact structure and resting perfusion. AB - BACKGROUND: Hippocampal volume reductions in major depression have been frequently reported. However, evidence for functional abnormalities in the same region in depression has been less clear. We investigated hippocampal function in depression using functional magnetic resonance imaging (fMRI) and neuropsychological tasks tapping spatial memory function, with complementing measures of hippocampal volume and resting blood flow to aid interpretation. METHOD: A total of 20 patients with major depressive disorder (MDD) and a matched group of 20 healthy individuals participated. Participants underwent multimodal magnetic resonance imaging (MRI): fMRI during a spatial memory task, and structural MRI and resting blood flow measurements of the hippocampal region using arterial spin labelling. An offline battery of neuropsychological tests, including several measures of spatial memory, was also completed. RESULTS: The fMRI analysis showed significant group differences in bilateral anterior regions of the hippocampus. While control participants showed task-dependent differences in blood oxygen level-dependent (BOLD) signal, depressed patients did not. No group differences were detected with regard to hippocampal volume or resting blood flow. Patients showed reduced performance in several offline neuropsychological measures. All group differences were independent of differences in hippocampal volume and hippocampal blood flow. CONCLUSIONS: Functional abnormalities of the hippocampus can be observed in patients with MDD even when the volume and resting perfusion in the same region appear normal. This suggests that changes in hippocampal function can be observed independently of structural abnormalities of the hippocampus in depression. PMID- 27192932 TI - Ageing and the pathogenesis of osteoarthritis. AB - Ageing-associated changes that affect articular tissues promote the development of osteoarthritis (OA). Although ageing and OA are closely linked, they are independent processes. Several potential mechanisms by which ageing contributes to OA have been elucidated. This Review focuses on the contributions of the following factors: age-related inflammation (also referred to as 'inflammaging'); cellular senescence (including the senescence-associated secretory phenotype (SASP)); mitochondrial dysfunction and oxidative stress; dysfunction in energy metabolism due to reduced activity of 5'-AMP-activated protein kinase (AMPK), which is associated with reduced autophagy; and alterations in cell signalling due to age-related changes in the extracellular matrix. These various processes contribute to the development of OA by promoting a proinflammatory, catabolic state accompanied by increased susceptibility to cell death that together lead to increased joint tissue destruction and defective repair of damaged matrix. The majority of studies to date have focused on articular cartilage, and it will be important to determine whether similar mechanisms occur in other joint tissues. Improved understanding of ageing-related mechanisms that promote OA could lead to the discovery of new targets for therapies that aim to slow or stop the progression of this chronic and disabling condition. PMID- 27192935 TI - Evolving Trends in Female to Male Incidence and Male Mortality of Primary Biliary Cholangitis. AB - Primary biliary cholangitis (PBC) has been regarded as female-predominant without evidence of gender difference in survival. We aimed to compare the overall survival, incidence and prevalence of PBC in two well defined population-based studies over a recent decade, considering also sex ratios and mortality. We have taken advantage of population-wide records, during 2000-2009, in Lombardia, Northern Italy, and Denmark. We focused on the incident cases of PBC, including gender and outcome, among 9.7 million inhabitants of Lombardia and 5.5 million of Denmark. In Lombardia there were 2,970 PBC cases with a female:male ratio of 2.3:1. The age/sex-adjusted annual incidence of PBC was 16.7 per million. Point prevalence was 160 per million on January 1(st) 2009. In Denmark there were 722 cases of incident PBC, female:male ratio was 4.2:1, and the annual incidence was 11.4 per million, a point prevalence of 115 per million in 2009. Cox regression multivariate analysis identified male sex as an independent predictor of all cause mortality in both Italian (HR 2.36) and Danish population (HR 3.04). Our data indicate for PBC a sex ratio significantly lower than previously cited, a reversal of the usual latitudinal difference in prevalence and a surprisingly higher overall mortality for male patients. PMID- 27192936 TI - Perturbation of gut bacteria induces a coordinated cellular immune response in the purple sea urchin larva. AB - The purple sea urchin (Strongylocentrotus purpuratus) genome sequence contains a complex repertoire of genes encoding innate immune recognition proteins and homologs of important vertebrate immune regulatory factors. To characterize how this immune system is deployed within an experimentally tractable, intact animal, we investigate the immune capability of the larval stage. Sea urchin embryos and larvae are morphologically simple and transparent, providing an organism-wide model to view immune response at cellular resolution. Here we present evidence for immune function in five mesenchymal cell types based on morphology, behavior and gene expression. Two cell types are phagocytic; the others interact at sites of microbial detection or injury. We characterize immune-associated gene markers for three cell types, including a perforin-like molecule, a scavenger receptor, a complement-like thioester-containing protein and the echinoderm-specific immune response factor 185/333. We elicit larval immune responses by (1) bacterial injection into the blastocoel and (2) seawater exposure to the marine bacterium Vibrio diazotrophicus to perturb immune state in the gut. Exposure at the epithelium induces a strong response in which pigment cells (one type of immune cell) migrate from the ectoderm to interact with the gut epithelium. Bacteria that accumulate in the gut later invade the blastocoel, where they are cleared by phagocytic and granular immune cells. The complexity of this coordinated, dynamic inflammatory program within the simple larval morphology provides a system in which to characterize processes that direct both aspects of the echinoderm specific immune response as well as those that are shared with other deuterostomes, including vertebrates. PMID- 27192937 TI - Emerging role of immunoproteasomes in pathophysiology. AB - The immunoproteasome is a proteasome variant that is found only in jawed vertebrates. It is responsible for degrading intracellular proteins to generate a major source of peptides with substantial major histocompatibility complex I binding affinity. The immunoproteasome also has roles in T-cell survival, differentiation and proliferation in various pathological conditions. In humans, any alteration in the expression, assembly or function of the immunoproteasome can lead to cancer, autoimmune disorders or inflammatory diseases. Although the roles of the immunoproteasome in cancer and neurodegenerative disorders have been extensively studied, its significance in other disease conditions has only recently become known. Therefore, there is renewed interest in the development of drugs, vaccines and biomarkers that target the immunoproteasome. The current review highlights the involvement of this complex in disease pathology in addition to the advances made in immunoproteasome research. PMID- 27192943 TI - Exceptional photosensitivity of a polyoxometalate-based charge-transfer hybrid material. AB - An unusual room-temperature light sensitivity was realized in a polyoxometalate based hybrid material due to cooperative multicomponent molecular charge-transfer interactions taking place in this material, mainly among POMs, NDIs, and other molecules. The functional pi-acidic NDI linkers and POM clusters in the discussed hybrid material were individually designed as photosensors and electron reservoirs. To propose a photo-induced charge-transfer mechanism, EPR, XPS, UV Vis and computational studies were carried out, and indicated the presence of active charge-transfer interactions among several of the components. PMID- 27192938 TI - Human cytomegalovirus pUL10 interacts with leukocytes and impairs TCR-mediated T cell activation. AB - Human cytomegalovirus (HCMV) is known to exert suppressive effects on the host immune system through expression of various viral genes, thus directly and indirectly affecting antiviral immunity of the infected individuals. We report here that HCMV UL10 encodes a protein (pUL10) with immunosuppressive properties. UL10 has been classified as a member of the HCMV RL11 gene family. Although pUL10 is known to be dispensable for viral replication in cultured cells, its amino acid sequence is well conserved among different HCMV isolates, suggesting that the protein has a crucial role in viral survival in the host environment. We show that pUL10 is cleaved from the cell surface of fibroblasts as well as epithelial cells and interacts with a cellular receptor ubiquitously expressed on the surface of human leukocytes, demonstrated by ex vivo cell-based assays and flow cytometric analyses on both lymphoid cell lines and primary blood cells. Furthermore, preincubation of peripheral blood mononuclear cells with purified pUL10 ectodomain results in significantly impaired proliferation and substantially reduced pro-inflammatory cytokine production, in particular in CD4+ T cells upon in vitro T-cell stimulation. The inhibitory effect of pUL10 is also observed on antigen receptor-mediated intracellular tyrosine phosphorylation in a T-cell line. Based on these observations, we suggest that pUL10 is a newly identified immunomodulatory protein encoded by HCMV. Further elucidation of interactions between pUL10 and the host immune system during HCMV may contribute to finding ways towards new therapies for HCMV infection. PMID- 27192941 TI - Large reversible caloric effect in FeRh thin films via a dual-stimulus multicaloric cycle. AB - Giant magnetocaloric materials are promising for solid-state refrigeration, as an alternative to hazardous gases used in conventional cooling devices. A giant magnetocaloric effect was discovered near room temperature in near-equiatomic FeRh alloys some years before the benchmark study in Gd5Si2Ge2 that launched the field. However, FeRh has attracted significantly less interest in cooling applications mainly due to irreversibility in magnetocaloric cycles associated with the large hysteresis of its first-order metamagnetic phase transition. Here we overcome the irreversibility via a dual-stimulus magnetic-electric refrigeration cycle in FeRh thin films via coupling to a ferroelectric BaTiO3 substrate. This experimental realization of a multicaloric cycle yields larger reversible caloric effects than either stimulus alone. While magnetic hysteretic losses appear to be reduced by 96% in dual-stimulus loops, we show that the losses are simply transferred into an elastic cycle, contrary to common belief. Nevertheless, we show that these losses do not necessarily prohibit integration of FeRh in practical refrigeration systems. Our demonstration of a multicaloric refrigeration cycle suggests numerous designs for efficient solid-state cooling applications. PMID- 27192939 TI - Subtle reproductive impairment through nitric oxide-mediated mechanisms in sea urchins from an area affected by harmful algal blooms. AB - The health of the sea urchin Paracentrotus lividus, a key species in the Mediterranean Sea, is menaced by several pressures in coastal environments. Here, we aimed at assessing the reproductive ability of apparently healthy P. lividus population in a marine protected area affected by toxic blooms of Ostreospsis cf. ovata. Wide-ranging analyses were performed in animals collected prior to and during the bloom, as well as at several times thereafter, during the reproductive season. Adults showed a low fertilization rate, along with high nitric oxide (NO) levels in the gonads and the nitration of the major yolk protein toposome, which is an important player in sea urchin development. Serious developmental anomalies were observed in the progeny, which persist several months after the bloom. NO levels were high in the different developmental stages, which also showed variations in the transcription of several genes that were found to be directly or indirectly modulated by NO. These results highlight subtle but important reproductive flaws transmitted from the female gonads to the offspring with the NO involvement. Despite a recovery along time after the bloom, insidious damages can be envisaged in the local sea urchin population, with possible reverberation on the whole benthic system. PMID- 27192944 TI - Mueller-matrix of laser-induced autofluorescence of polycrystalline films of dried peritoneal fluid in diagnostics of endometriosis. AB - This research presents investigation results of the diagnostic efficiency of an azimuthally stable Mueller-matrix method of analysis of laser autofluorescence of polycrystalline films of dried uterine cavity peritoneal fluid. A model of the generalized optical anisotropy of films of dried peritoneal fluid is proposed in order to define the processes of laser autofluorescence. The influence of complex mechanisms of both phase (linear and circular birefringence) and amplitude (linear and circular dichroism) anisotropies is taken into consideration. The interconnections between the azimuthally stable Mueller-matrix elements characterizing laser autofluorescence and different mechanisms of optical anisotropy are determined. The statistical analysis of coordinate distributions of such Mueller-matrix rotation invariants is proposed. Thereupon the quantitative criteria (statistic moments of the first to the fourth order) of differentiation of polycrystalline films of dried peritoneal fluid, group 1 (healthy donors) and group 2 (uterus endometriosis patients), are determined. PMID- 27192942 TI - Therapeutic Blockade of Immune Complex-Mediated Glomerulonephritis by Highly Selective Inhibition of Bruton's Tyrosine Kinase. AB - Lupus nephritis (LN) is a potentially dangerous end organ pathology that affects upwards of 60% of lupus patients. Bruton's tyrosine kinase (BTK) is important for B cell development, Fc receptor signaling, and macrophage polarization. In this study, we investigated the effects of a novel, highly selective and potent BTK inhibitor, BI-BTK-1, in an inducible model of LN in which mice receive nephrotoxic serum (NTS) containing anti-glomerular antibodies. Mice were treated once daily with vehicle alone or BI-BTK-1, either prophylactically or therapeutically. When compared with control treated mice, NTS-challenged mice treated prophylactically with BI-BTK-1 exhibited significantly attenuated kidney disease, which was dose dependent. BI-BTK-1 treatment resulted in decreased infiltrating IBA-1+ cells, as well as C3 deposition within the kidney. RT-PCR on whole kidney RNA and serum profiling indicated that BTK inhibition significantly decreased levels of LN-relevant inflammatory cytokines and chemokines. Renal RNA expression profiling by RNA-seq revealed that BI-BTK-1 dramatically modulated pathways related to inflammation and glomerular injury. Importantly, when administered therapeutically, BI-BTK-1 reversed established proteinuria and improved renal histopathology. Our results highlight the important role for BTK in the pathogenesis of immune complex-mediated nephritis, and BTK inhibition as a promising therapeutic target for LN. PMID- 27192946 TI - Systematic Review of Submaximal Cycle Tests to Predict, Monitor and Optimize Cycling Performance. AB - Finding the optimal balance between high training loads and recovery is a constant challenge for cyclists and their coaches. Monitoring improvements in performance and levels of fatigue is recommended in order to correctly adjust training to ensure optimal adaptation. However, many performance tests require a maximal or exhaustive effort, which reduces their real-world application. The purpose of this review was to investigate the development and use of submaximal cycling tests which can be used to predict and monitor cycling performance and training status. Twelve studies met the inclusion criteria and three separate submaximal cycling tests were identified from within those studies. Submaximal variables including; gross mechanical efficiency, VO2, heart rate, lactate, predicted time to exhaustion, RPE, power output and heart rate recovery were the components of the three tests. Predicted time to exhaustion, submaximal power output, RPE and heart rate recovery appear to have the most value for monitoring improvements in performance and indicate a state of fatigue. This literature review shows that several submaximal cycle tests have been developed over the last decade with the aim to predict, monitor and optimize cycling performance. To be able to conduct a submaximal test on a regular basis, a submaximal test needs to be short in duration and as minimally non-invasive as possible. In addition, a test should capture multiple variables and use multi-variate analyses to interpret the submaximal outcomes correctly and alter training prescription if needed. PMID- 27192947 TI - Psychological trauma after the Great East Japan Earthquake. AB - The Great East Japan Earthquake (GEJE) struck the northeastern part of Japan on 11 March 2011 and triggered a devastating tsunami, causing widespread destruction along the coast of northeastern Japan. The tsunami also led to an accident at the Fukushima Daiichi nuclear power plant. Incidents occurring in such major disasters are known to lead to psychological trauma. This paper has summarized English-language documentation regarding GEJE-related psychological trauma or post-traumatic stress disorder (PTSD). Research thus far has reported the possibility of higher probable PTSD prevalence among residents of the GEJE areas than in the average Japanese population during normal times. At the very least, many people have experienced trauma symptoms at self-recognition levels 1 year or longer after the disaster. It appears that the percentage of persons with high PTSD risk was higher in regions with radiation-related impacts than in regions where the main damage was caused by the earthquake and tsunami. Results have not been limited to showing relations between severe exposure to a traumatic event and PTSD symptoms but also show that a variety of factors, including social factors, has been shown to interact with PTSD symptoms. The fact that Japanese society as a whole united against the trauma of the GEJE may have worked to minimize the effects of trauma. To grasp a full picture of the effects of psychological trauma due to the GEJE, further surveys and research are necessary. It will be necessary to continue engagements related to these problems and issues into the future. PMID- 27192945 TI - Proteomic profiling of cellulase-aid-extracted membrane proteins for functional identification of cellulose synthase complexes and their potential associated- components in cotton fibers. AB - Cotton fibers are an excellent model for understanding of cellulose biosynthesis in higher plants. In this study, we determined a high cellulose biosynthesis activity in vitro by optimizing biochemical reaction conditions in cotton fibers. By adding a commercial cellulase enzyme into fibers extraction process, we extracted markedly higher levels of GhCESA1 and GhCESA8 proteins and observed an increase in beta-1,4-glucan and beta-1,3-glucan products in vitro. LC-MS/MS analysis of anti-GhCESA8-immunoprecipitated proteins showed that 19 proteins could be found in three independent experiments including four CESAs (GhCESA1,2,7,8), five well-known non-CESA proteins, one callose synthase (CALS) and nine novel proteins. Notably, upon the cellulase treatment, four CESAs, one CALS and four novel proteins were measured at relatively higher levels by calculating total peptide counts and distinct peptide numbers, indicating that the cellulase-aid-extracted proteins most likely contribute to the increase in beta-glucan products in vitro. These results suggest that the cellulase treatment may aid to release active cellulose synthases complexes from growing glucan chains and make them more amenable to extraction. To our knowledge, it is the first time report about the functional identification of the potential proteins that were associated with plant cellulose and callose synthases complexes by using the cellulase-aided protein extraction. PMID- 27192949 TI - Hypnosis for pain management during labour and childbirth. AB - BACKGROUND: This review is one in a series of Cochrane reviews investigating pain management for childbirth. These reviews all contribute to an overview of systematic reviews of pain management for women in labour, and share a generic protocol. This review updates an earlier version of the review of the same title. OBJECTIVES: To examine the effectiveness and safety of hypnosis for pain management during labour and childbirth. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2015) and the reference lists of primary studies and review articles. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTS comparing preparation for labour using hypnosis and/or use of hypnosis during labour, with or without concurrent use of pharmacological or non-pharmacological pain relief methods versus placebo, no treatment or any analgesic drug or technique. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trial quality. Where possible we contacted study authors seeking additional information about data and methodology. MAIN RESULTS: We included nine trials randomising a total of 2954 women. The risk of bias in trials was variable, there were several well-designed large trials and some trials where little was reported about trial design. Although eight of the nine trials assessed antenatal hypnotherapy, there were considerable differences between these trials in timing and technique. One trial provided hypnotherapy during labour. In this updated review we compared hypnosis interventions with all control groups (main comparison) and also with specific control conditions: standard care (nine RCTs), supportive counselling (two RCTs) and relaxation training (two RCTs).In the main comparison, women in the hypnosis group were less likely to use pharmacological pain relief or analgesia than those in the control groups, (average risk ratio (RR) 0.73, 95% CI 0.57 to 0.94, eight studies, 2916 women; very low-quality evidence; random effects model). There were no clear differences between women in the hypnosis group and those in the control groups for most of the other primary outcomes. There were no clear differences for sense of coping with labour (MD 0.22, 95% CI 0.14 to 0.58, one study, 420 women; low-quality evidence) or spontaneous vaginal birth (average RR 1.12, 95% CI 0.96 to 1.32, six studies, 2361 women; low-quality evidence; random-effects model). There were no clear differences for satisfaction with pain relief (measured on a seven-point scale two weeks postnatally) for women in the hypnosis group who also received pethidine (MD 0.41, 95% CI -0.45 to 1.27; one study, 72 women), Entonox (MD 0.19, 95% CI -0.19 to 0.57; one study, 357 women), self-hypnosis (MD 0.28, 95% CI -0.32 to 0.88; one study, 160 women), or epidural (MD -0.03, 95% CI -0.40 to 0.34; one study, 127 women), but a slight benefit in favour of hypnosis was seen for women who received water immersion (MD 0.52, 95% CI 0.04 to 1.00; one study, 174 women (all low-quality evidence). There were no clear differences for satisfaction with pain relief when it was measured as the number of women who reported they had adequate pain relief (risk ratio (RR) 1.06, 95% confidence interval (CI) 0.94 to 1.20, one study, 264 women; low quality evidence). It should be noted that for pharmacological pain relief and spontaneous vaginal birth, there was evidence of considerable statistical heterogeneity, which could not be fully explained by subgroup analysis.For this review's secondary outcomes, no clear differences were found between women in the hypnosis group and women in the control groups for most outcomes where data were available. There was mixed evidence regarding benefits for women in the hypnosis group compared with all control groups for pain intensity, satisfaction with childbirth experience and postnatal depression. For each of these outcomes, data from more than one trial were available for analysis but could not be combined due to differences in measurement methods. There was evidence that fewer women in the hypnosis group stayed in hospital for more than two days after the birth but this finding was based on one small study (RR 0.11, 95% CI 0.02 to 0.83). No clear differences between women in the hypnosis group and the control groups were found for the other secondary outcomes where data were available.In the comparisons of hypnosis with specific types of control conditions: standard care, supportive counselling and relaxation training, there were no clear differences found between women in the hypnosis group and those in the standard care control groups or the relaxation control groups for the primary outcomes. Compared with the women in the supportive counselling control group, women in the hypnosis group were less likely to use pharmacological analgesia (average RR 0.48, 95% CI 0.32 to 0.73, two studies, 562 women). They were also more likely to have a spontaneous vaginal birth (RR 2.42, 95% CI 1.43 to 4.07), although this finding was based on the results of one small study. Overall these new comparisons displayed much less statistical heterogeneity than the comparison including all control groups. AUTHORS' CONCLUSIONS: There are still only a relatively small number of studies assessing the use of hypnosis for labour and childbirth. Hypnosis may reduce the overall use of analgesia during labour, but not epidural use. No clear differences were found between women in the hypnosis group and those in the control groups for satisfaction with pain relief, sense of coping with labour or spontaneous vaginal birth. Not enough evidence currently exists regarding satisfaction with pain relief or sense of coping with labour and we would encourage any future research to prioritise the measurement of these outcomes. The evidence for the main comparison was assessed using GRADE as being of low quality for all the primary outcomes with downgrading decisions due to concerns regarding inconsistency of the evidence, limitations in design and imprecision. Further research is needed in the form of large, well-designed randomised controlled trials to assess whether hypnosis is of value for pain management during labour and childbirth. PMID- 27192948 TI - Choroidal thickness does not predict visual acuity in young high myopes. AB - PURPOSE: To investigate the influence of choroidal thickness (CT) on visual acuity (VA) in young persons with extremely high myopia. METHODS: We conducted a case-control study of young men with extremely high myopia and controls with emmetropia recruited from a mandatory medical eye review for employment purposes. Retinal and choroidal imaging was performed using enhanced depth imaging (EDI) spectral-domain optical coherence tomography (SD-OCT). RESULTS: We included 105 extremely high myopic subjects with spherical equivalent (SE) -10 dioptre (D) or worse and 50 emmetropic subjects with SE less than 0.5 D. The mean SE was -11.56 +/- 2.04 D (range, -10 to -23 D) for myopic group and 0.14 +/- 0.25 D for emmetropic group. The mean age of included myopic and emmetropic subjects was 21.51 +/- 1.22 years and 21.96 +/- 0.89 years, respectively. In the univariate analysis, subfoveal CT was significantly associated with best-corrected visual acuity (BCVA) (beta = -0.039, p = 0.015). However, in the multiple linear regression analysis, after adjusting for SE and presence of any pathological myopia lesions such as posterior staphyloma, lacquer cracks or chorioretinal atrophy, subfoveal CT was not independently associated with BCVA (p = 0.937). CONCLUSION: Extremely high myopic eyes had thinner choroid, but CT was not an independent predictor of VA. Other factors related to myopia are likely responsible for the diminished VA in young extremely high myopic eyes. PMID- 27192950 TI - Targeting CTLA-4, PD-L1 and IDO to modulate immune responses in vitiligo. AB - For decades, an extensive debate is continued on the pathophysiology of vitiligo. Numerous hypotheses have been put forward, and many supported by well-documented arguments. Regardless of the initiating steps, most experts agree that an immune based melanocyte destruction is responsible for the final steps leading to epidermal depigmentation. It is remarkable that currently the only therapeutic approach to counter this phenomenon consists of non-specific local and systemic immunosuppressants. Immunotherapy for melanoma reveals that targeting factors involved in peripheral tolerance are sufficient to break the natural defense mechanisms to develop skin depigmentations. Therapeutically enhancing these immune checkpoints seems therefore a promising long-term therapy for vitiligo. In this viewpoint, we propose this strategy as a promising therapeutic option for vitiligo. Several approaches are proposed with a focus on cytotoxic T-lymphocyte associated protein 4, programmed death ligand-1 and indoleamine 2,3-dioxygenase. PMID- 27192951 TI - Maturing insights into the genetic architecture of neurodevelopmental disorders - from common and rare variant interplay to precision psychiatry. AB - The categorisation of neurodevelopmental and psychiatric disorders by clinical syndromes, rather than by aetiology, continues to obstruct progress in biomarker identification as well as innovative drug development and effective treatment in general. There is a decisive move to think of neurodevelopmental disorders as a spectrum rather than discrete categorical entities. We might call them neurodevelopmental spectrum disorders (NSDs) ranging from intellectual disability (ID) to autism (ASD), and attention-deficit/hyperactivity disorder (ADHD) (Kiser, Rivero, & Lesch, ). PMID- 27192952 TI - Editorial Perspective: Psychological stress and epigenetic aging - what can we learn and how can we prevent? AB - Psychological stress can exert a lasting impact on the aging process. This hypothesis, long posited by Hans Selye, has been supported by evidence linking stressors with several aging-related disease phenotypes. However, little is known about the molecular mechanisms underlying this association. Among plausible mechanisms linking stress and aging, evidence supports the role of epigenetic modifications, a set of molecular processes that can be induced by environmental stressors and regulate gene expression without altering the underlying genetic sequence. In particular, recent evidence shows that psychological stress can accelerate epigenetic aging, a measure based on DNA methylation prediction of chronological age that shows promise as biomarker of aging. Some studies further suggest that epigenetic aging could be modifiable, albeit others contradict this hypothesis. Future studies will need to determine the preventability or reversibility of epigenetic aging in response to distinct interventions and the potential clinical implications of such a prevention or reversal. PMID- 27192953 TI - Commentary: Switching the zoom on the ADHD research lens - a reflection on Leventakou et al. (2016). AB - The study by Leventakou and colleagues is emblematic of a welcome change in focus in attention-deficit/hyperactivity disorder (ADHD) research. First, the authors focused on the overlooked association between ADHD and aberrant eating patterns, reflecting an emerging change in the conceptualization of ADHD as a condition affecting not only high-level cognitive processes but also more basic functions such as eating and sleeping, as well as the underlying complex metabolic and possibly inflammatory pathways. Second, the authors focused, for the first time, on the relationship between ADHD and eating disorders in preschoolers, which is of relevance for the design of preventive strategies. Third, they zoomed closely to several types of aberrant eating behaviours; besides confirming the association of ADHD symptoms to emotional overeating, they also found an intriguing relationship between impulsivity and food fussiness. Further changes in perspective focusing on the underlying mechanisms, as well as using a wide angle lens to capture the longitudinal relationship between ADHD and aberrant eating behaviours will not only provide a more detailed (clinical) picture of individuals with ADHD but will also hopefully lead to more effective preventive/treatment strategies. PMID- 27192954 TI - Commentary: Networks of peers, genes, and explanations - reflections on Szekely et al. (2016). AB - Much has been learned about the origins and effects of peer relationships on the health and well-being of children, adolescents, and adults. This commentary on Szekely et al. examines the role of genetics research on peer relationships, and the arising methodological and conceptual questions. Research findings on the genetics of peer networks illustrate how genetic influences may shape complex and dynamic phenotypes. Equally complex is the application of these findings for theory and practice. PMID- 27192955 TI - Commentary: Cognitive and emotional empathy in transdiagnostic research - reflections on Klapwijk et al. (2016). AB - Evidence across multiple disorders indicates that empathy is a transdiagnostic dimension of psychopathology. Klapwijk et al.'s (2016) functional MRI study examines whether autism spectrum disorder (ASD) and conduct disorder (CD) can be distinguished by the constructs of 'cognitive' and 'emotional' empathy - with the former focusing on accurate emotion perception and the latter on shared affective experience. This commentary examines the implications of the cognitive/emotional empathy distinction, and how it fits with existing accounts of perceptual differences in ASD. Cognitive empathy overlaps substantially with the constructs of emotion perception and Theory of Mind - both well studied among individuals with ASD, but generally viewed as fairly distinct from empathy. CD, on the other hand, is typically not associated with frank perceptual deficits. Although the brain imaging data from this study do not provide strong support for the constructs of cognitive and emotional empathy, the general approach used in this study is precisely the kind needed to test the validity and utility of transdiagnostic mechanisms of psychopathology. PMID- 27192957 TI - Erratum. PMID- 27192956 TI - Commentary: Objective aids for the assessment of ADHD - further clarification of what FDA approval for marketing means and why NEBA might help clinicians. A response to Arns et al. (2016). AB - Neuropsychiatric EEG-Based ADHD Assessment Aid (NEBA) is an EEG-based device designed to aid in the diagnostic process for ADHD by identifying individuals less likely to have ADHD by virtue of a lower theta/beta ratio. In using NEBA as an example, the Arns et al. commentary misstates the purpose of NEBA, which is to widen the differential rather than to make the diagnosis. Arns et al. caution about missing an ADHD diagnosis, but fail to mention the impact of overdiagnosis. If we are to advance our knowledge of the etiology and pathophysiology of ADHD, as well as develop tailored treatments and ultimately improve outcomes for ADHD, then biomarkers and objective assessment aids such as NEBA are needed to improve and refine diagnostic accuracy beyond symptom description and clinical history. PMID- 27192958 TI - Contextualizing individual differences in error monitoring: Links with impulsivity, negative affect, and conscientiousness. AB - The error-related negativity (ERN) is a neural measure of error processing that has been implicated as a neurobehavioral trait and has transdiagnostic links with psychopathology. Few studies, however, have contextualized this traitlike component with regard to dimensions of personality that, as intermediate constructs, may aid in contextualizing links with psychopathology. Accordingly, the aim of this study was to examine the interrelationships between error monitoring and dimensions of personality within a large adult sample (N = 208). Building on previous research, we found that the ERN relates to a combination of negative affect, impulsivity, and conscientiousness. At low levels of conscientiousness, negative urgency (i.e., impulsivity in the context of negative affect) predicted an increased ERN; at high levels of conscientiousness, the effect of negative urgency was not significant. This relationship was driven specifically by the conscientiousness facets of competence, order, and deliberation. Links between personality measures and error positivity amplitude were weaker and nonsignificant. Post-error slowing was also related to conscientiousness, as well as a different facet of impulsivity: lack of perseverance. These findings suggest that, in the general population, error processing is modulated by the joint combination of negative affect, impulsivity, and conscientiousness (i.e., the profile across traits), perhaps more so than any one dimension alone. This work may inform future research concerning aberrant error processing in clinical populations. PMID- 27192959 TI - Association of NOS2 and NOS3 gene polymorphisms with susceptibility to type 2 diabetes mellitus and diabetic nephropathy in the Chinese Han population. AB - Inducible nitric oxide synthase (NOS2) and endothelial nitric oxide synthase (NOS3) gene play important roles in the susceptibility to type 2 diabetes mellitus (T2DM). The present study aims to detect the potential association of NOS2 and NOS3 gene polymorphisms with the susceptibility toT2DM and diabetic nephropathy (DN) in the Chinese Han population. Four hundred and ninety T2DM patients and 485 healthy controls were enrolled in this case-control study. The genotypes of NOS2 and NOS3 gene polymorphisms were analyzed by the polymerase chain reaction (PCR)-ligase detection reaction (LDR) method. Our data demonstrated that the NOS2 rs2779248 and NOS2 rs1137933 genetic polymorphisms were significantly associated with the increased susceptibility to T2DM in the heterozygote comparison, dominant model, and allele contrast; and NOS3 rs3918188 genetic polymorphism was significantly associated with the increased susceptibility to T2DM in the homozygote comparison and recessive model. The allele-C and genotype-TC of NOS2 rs2779248, allele-A and genotype-GA of NOS2 rs1137933 and genotype-AA of NOS3 rs3918188 genetic polymorphisms might be the risk factors for increasing the susceptibility to T2DM. And a significant haplotype effect of NOS2 rs10459953/C- rs1137933/G- rs2779248/T was found between T2DM cases and controls. Moreover, NOS3 rs1800783 polymorphism was significantly associated with the increased susceptibility to DN in the heterozygote comparison, recessive model and allele contrast. At last, a positive correlation of family history of diabetes with NOS3 rs11771443 polymorphism was found in DN. These preliminary findings indicate that the NOS2 rs2779248, NOS2 rs1137933, and NOS3 rs3918188 genetic polymorphisms are potentially related to the susceptibility to T2DM, and the rs1800783 polymorphism might be considered as genetic risk factors for diabetic nephropathy, and family history of diabetes was closely associated with rs11771443 polymorphism in DN, and the genetic variants might be used as molecular markers for evaluating the risk of T2DM and diabetic nephropathy. (c) 2016 IUBMB Life, 68(7):516-525, 2016. PMID- 27192960 TI - Functional dichotomy of Vdelta2 gammadelta T cells in chronic hepatitis C virus infections: role in cytotoxicity but not for IFN-gamma production. AB - Vdelta2 gammadelta (Vdelta2) T cells, a major human gammadelta T cell subset, exhibit broad anti-tumor and anti-infective activity; however, their precise role in chronic hepatitis C virus (HCV) infections remains unclear. In this study, we analyzed the phenotype and function of Vdelta2 T cells in 43 HCV-infected patients compared to 39 healthy controls (HCs). Vdelta2 T cells from HCV-infected patients were activated and differentiated into effector cells. Vdelta2 T cells in patients expressed significantly higher levels of natural killer (NK) cell markers CD56 and CD16 than in HCs, acquiring cytotoxic NK-like phenotype. The Vdelta2 T cell phenotype was associated with increased cytolytic effector molecules expression in HCV-infected patients with elevated serum ALT levels. Surprisingly, Vdelta2 T cells in patients had a markedly impaired capacity to produce IFN-gamma. Further in vitro and in vivo analysis showed that interferon alpha, which was induced during HCV infection, caused Vdelta2 T cell function bias toward cytotoxicity. These results suggest a functional dichotomy for Vdelta2 T cells in chronic HCV infections: a role in cytotoxicity but not for IFN gamma production, which may contribute to both the liver inflammation and HCV persistence. PMID- 27192962 TI - Strongly Coupled Cyclometalated Ruthenium Triarylamine Chromophores as Sensitizers for DSSCs. AB - A series of anchor-functionalized cyclometalated bis(tridentate) ruthenium(II) triarylamine hybrids [Ru(dbp-X)(tctpy)](2-) [2 a](2-) -[2 c](2-) (H3 tctpy=2,2';6',2''-terpyridine-4,4',4''-tricarboxylic acid; dpbH=1,3 dipyridylbenzene; X=N(4-C6 H4 OMe)2 ([2 a](2-) ), NPh2 ([2 b](2-) ), N-carbazolyl [2 c](2-) ) was synthesized and characterized. All complexes show broad absorption bands in the range 300-700 nm with a maximum at about 545 nm. Methyl esters [Ru(Me3 tctpy)(dpb-X)](+) [1 a](+) -[1 c](+) are oxidized to the strongly coupled mixed-valent species [1 a](2+) -[1 c](2+) and the Ru(III) (aminium) complexes [1 a](3+) -[1 c](3+) at comparably low oxidation potentials. Theoretical calculations suggest an increasing spin delocalization between the metal center and the triarylamine unit in the order [1 a](2+) <[1 b](2+) <[1 c](2+) . Solar cells were prepared with the saponified complexes [2 a](2-) -[2 c](2-) and the reference dye N719 as sensitizers using the I3 (-) /I(-) couple and [Co(bpy)3 ](3+/2+) and [Co(ddpd)2 ](3+/2+) couples as [B(C6 F5 )4 ](-) salts as electrolytes (bpy=2,2'-bipyridine; ddpd=N,N'-dimethyl-N,N'-dipyridin-2-yl pyridine-2,6-diamine). Cells with [2 c](2-) and I3 (-) /I(-) electrolyte perform similarly to cells with N719. In the presence of cobalt electrolytes, all efficiencies are reduced, yet under these conditions [2 c](2-) outperforms N719. PMID- 27192963 TI - Exploring factors affecting registered nurses' pursuit of postgraduate education in Australia. AB - The aim of this study was to explore the factors influencing registered nurses' pursuit of postgraduate education in specialty nursing practice in Australia. Despite the increased requirement for postgraduate education for advanced practice, little has been reported on the contributory factors involved in the decision to undertake further education. The Nurses' Attitudes Towards Postgraduate Education instrument was administered to 1632 registered nurses from the Nurses and Midwives e-Cohort Study across Australia, with a response rate of 35.9% (n = 568). Data reduction techniques using principal component analysis with varimax rotation were used. The analysis identified a three-factor solution for 14 items, accounting for 52.5% of the variance of the scale: "facilitators," "professional recognition," and "inhibiting factors." Facilitators of postgraduate education accounted for 28.5% of the variance, including: (i) improves knowledge; (ii) increases nurses' confidence in clinical decision making; (iii) enhances nurses' careers; (iv) improves critical thinking; (v) improves nurses' clinical skill; and (vi) increased job satisfaction. This new instrument has potential clinical and research applications to support registered nurses' pursuit of postgraduate education. PMID- 27192964 TI - Valley polarization and p-/n-type doping of monolayer WTe2 on top of Fe3O4(111). AB - The electronic properties of monolayer WTe2 on top of Fe3O4(111) are investigated by density functional theory. We find that the substrate termination of Fe3O4(111) can switch the conductivity of monolayer WTe2 from the p- to n-type. However, the stacking pattern can critically influence its electronic structure. For Fe(A)-terminated interfaces, stronger-bonding models show Fermi level pinning. Additionally, the time-reversal symmetry is broken by the proximity that leads to valley polarization. With particular stacking patterns, large valley splittings of 139, -76 and -72 meV are obtained for Fe(A)-, Fe(B)- and O terminated models, respectively. Moreover, Fe(B)- and O-terminated ones have more applicable significance for valleytronics as no interference of the interface state appears at the valence band maximum. We demonstrate that proximity to a room-temperature ferromagnet is a convenient way to obtain valley polarization and adjust the conductivity of monolayer WTe2. PMID- 27192961 TI - How motif environment influences transcription factor search dynamics: Finding a needle in a haystack. AB - Transcription factors (TFs) have to find their binding sites, which are distributed throughout the genome. Facilitated diffusion is currently the most widely accepted model for this search process. Based on this model the TF alternates between one-dimensional sliding along the DNA, and three-dimensional bulk diffusion. In this view, the non-specific associations between the proteins and the DNA play a major role in the search dynamics. However, little is known about how the DNA properties around the motif contribute to the search. Accumulating evidence showing that TF binding sites are embedded within a unique environment, specific to each TF, leads to the hypothesis that the search process is facilitated by favorable DNA features that help to improve the search efficiency. Here, we review the field and present the hypothesis that TF-DNA recognition is dictated not only by the motif, but is also influenced by the environment in which the motif resides. PMID- 27192965 TI - Identification of a novel HLA-DRB1*07 allele, HLA-DRB1*07:01:19. AB - HLA-DRB1*07:01:19 differs from DRB1*07:01:01:01 by a single nucleotide substitution at position 261 of exon 2. PMID- 27192966 TI - Recognising and referring children exposed to domestic abuse: a multi professional, proactive systems-based evaluation using a modified Failure Mode and Effects Analysis (FMEA). AB - Failure Modes and Effects Analysis (FMEA) is a prospective quality assurance methodology increasingly used in healthcare, which identifies potential vulnerabilities in complex, high-risk processes and generates remedial actions. We aimed, for the first time, to apply FMEA in a social care context to evaluate the process for recognising and referring children exposed to domestic abuse within one Midlands city safeguarding area in England. A multidisciplinary, multi agency team of 10 front-line professionals undertook the FMEA, using a modified methodology, over seven group meetings. The FMEA included mapping out the process under evaluation to identify its component steps, identifying failure modes (potential errors) and possible causes for each step and generating corrective actions. In this article, we report the output from the FMEA, including illustrative examples of the failure modes and corrective actions generated. We also present an analysis of feedback from the FMEA team and provide future recommendations for the use of FMEA in appraising social care processes and practice. Although challenging, the FMEA was unequivocally valuable for team members and generated a significant number of corrective actions locally for the safeguarding board to consider in its response to children exposed to domestic abuse. PMID- 27192967 TI - Re: Atomic force microscopy and scanning electron microscopy analysis of daily disposable limbal ring contact lenses. PMID- 27192968 TI - Response to RE: Atomic force microscopy and scanning electron microscopy analysis of daily disposable limbal ring contact lenses. PMID- 27192969 TI - Dasatinib in imatinib-resistant or -intolerant chronic-phase, chronic myeloid leukemia patients: 7-year follow-up of study CA180-034. AB - Dasatinib was approved at 100 mg once daily for imatinib-resistant or -intolerant patients with chronic myeloid leukemia (CML) in chronic phase, based on results of the phase 3 CA180-034 (NCT00123474) study. Here we present the final 7-year analysis of this pivotal study, the longest follow-up to date of any second generation BCR-ABL1 tyrosine kinase inhibitor (TKI). Patients (n = 670) with imatinib-resistant or -intolerant CML in chronic phase received dasatinib. Nineteen percent of patients continued on study treatment, with a greater proportion in the 100 mg once daily arm remaining on therapy. Seven-year rates for major molecular response (MMR), progression-free survival (PFS), and overall survival (OS) were similar across doses; MMR, PFS, and OS results were 46, 42, and 65% at 100 mg once daily, respectively. Improved PFS and OS rates were reported in patients who achieved BCR-ABL1 <=10% at 3 and 6 months. No new safety signals were identified. The incidence of drug-related pleural effusion was 28% at 100 mg once daily and 35% at the other three dose groups. Incidence of drug related pulmonary hypertension and pulmonary arterial hypertension remained low (<=3% across all doses). Arterial ischemic events occurred in <=4% of patients across all doses. These data support the long-term efficacy and well-established safety profile of dasatinib for patients with imatinib-resistant or -intolerant CML in chronic phase. Am. J. Hematol. 91:869-874, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27192970 TI - Intraindividual dynamics of transcriptome and genome-wide stability of DNA methylation. AB - Cytosine methylation at CpG dinucleotides is an epigenetic mechanism that affects the gene expression profiles responsible for the functional differences in various cells and tissues. Although gene expression patterns are dynamically altered in response to various stimuli, the intraindividual dynamics of DNA methylation in human cells are yet to be fully understood. Here, we investigated the extent to which DNA methylation contributes to the dynamics of gene expression by collecting 24 blood samples from two individuals over a period of 3 months. Transcriptome and methylome association analyses revealed that only ~2% of dynamic changes in gene expression could be explained by the intraindividual variation of DNA methylation levels in peripheral blood mononuclear cells and purified monocytes. These results showed that DNA methylation levels remain stable for at least several months, suggesting that disease-associated DNA methylation markers are useful for estimating the risk of disease manifestation. PMID- 27192971 TI - Transplantation of Declined Liver Allografts Following Normothermic Ex-Situ Evaluation. AB - The demand for liver transplantation (LT) exceeds supply, with rising waiting list mortality. Utilization of high-risk organs is low and a substantial number of procured livers are discarded. We report the first series of five transplants with rejected livers following viability assessment by normothermic machine perfusion of the liver (NMP-L). The evaluation protocol consisted of perfusate lactate, bile production, vascular flows, and liver appearance. All livers were exposed to a variable period of static cold storage prior to commencing NMP-L. Four organs were recovered from donors after circulatory death and rejected due to prolonged donor warm ischemic times; one liver from a brain-death donor was declined for high liver function tests (LFTs). The median (range) total graft preservation time was 798 (range 724-951) min. The transplant procedure was uneventful in every recipient, with immediate function in all grafts. The median in-hospital stay was 10 (range 6-14) days. At present, all recipients are well, with normalized LFTs at median follow-up of 7 (range 6-19) months. Viability assessment of high-risk grafts using NMP-L provides specific information on liver function and can permit their transplantation while minimizing the recipient risk of primary graft nonfunction. This novel approach may increase organ availability for LT. PMID- 27192972 TI - Manifesting Subtle Differences of Neutral Hydrophilic Guest Isomers in a Molecular Container by Phase Transfer. AB - Achieving strong host-guest interactions between synthetic hosts and hydrophilic guests in solution is challenging because solvation effects overwhelm other effects. To resolve this issue, we transferred complexes of cucurbit[7]uril (CB[7]) and monosaccharides to the gas phase and report here their intrinsic host guest chemistry in the absence of solvation effects. It was observed that effective host-guest interactions in the gas phase mediated by ammonium cations allow the differentiation of the monosaccharide isomers in complex with CB[7] upon vibrational excitation. The potential of the unique observation was extended to a quantitative supramolecular analytical method for the monosaccharide guests. The combination of host-guest chemistry and phase transfer presented in this study is an effective approach to overcome current limitations in supramolecular chemistry. PMID- 27192973 TI - Effect and immediate after-effect of lightly gripping the cane on postural sway. AB - BACKGROUND: This study investigated the effect and after-effect of lightly touching a real cane on postural sway and ankle muscle activity. METHOD: Participants performed a single-leg stance (SLS) task with their eyes closed for 30 s under three tasks. In the first and third tasks, the participants performed a normal SLS. In the second task, the participants in light-grip group (n = 11) were asked to perform SLS while lightly gripping a cane with their hand. The participants in depend-on-cane group (n = 11) were asked to support their own body with a cane. RESULTS: Postural sway during a single-leg stance is decreased by light gripping and is accompanied by decreased co-contraction of the ankle joint muscles. If a participant lightly gripped a cane, postural sway decreased not only during the light gripping but also immediately after the withdrawal of the cane. Although postural sway and co-contraction in the depend-on-cane group were significantly decreased during the second task compared to the first task, they were not significantly changed between the first and third tasks. CONCLUSION: These results suggest that lightly gripped cane provides a haptic sensory cue that can be used to assist postural control mechanisms due to enhanced perception of self-motion through sensory interaction with the environment through the cane. Further, the haptic sensory cue during postural maintenance might be promoted as a practice effect of postural control. PMID- 27192975 TI - Macular Retinal Ganglion Cell Layer Thickness Is Not Reduced in Patients with Obstructive Sleep Apnea. AB - PURPOSE: To evaluate macular ganglion cell layer (GCL) and ganglion cell-inner plexiform layer (GCIPL) thicknesses in patients with obstructive sleep apnea (OSA) syndrome. METHODS: 73 OSA patients and 67 age-matched controls were consecutively and prospectively enrolled. All participants underwent at least one reliable standard automated perimetry (SAP) and were imaged with spectral-domain optical coherence tomography (OCT) using two different devices. The OCT parameters were compared between groups, and Pearson correlations between main indices of SAP and OCT parameters were calculated. RESULTS: The pattern standard deviation of SAP was higher in the OSA group (p = 0.001). Mean GCIPL thickness was 82.99 +/- 10.30 and 80.78 +/- 12.15 um in the control and OSA groups, respectively (p = 0.25), and GCL thickness was 44.93 +/- 11.42 um in the control group and 48.81 +/- 10.85 um in OSA individuals (p = 0.47). Pearson correlations between the GCIPL-GCL measurements and the main indices of SAP were not significant. CONCLUSIONS: Neither GCIPL nor GCL thickness were reduced in OSA subjects compared with healthy individuals. Retinal sensitivity evaluated with SAP was however decreased in OSA patients. PMID- 27192974 TI - The Bcl-2 homologue Buffy rescues alpha-synuclein-induced Parkinson disease-like phenotypes in Drosophila. AB - BACKGROUND: In contrast to the complexity found in mammals, only two Bcl-2 family genes have been found in Drosophila melanogaster including the pro-cell survival, human Bok-related orthologue, Buffy. The directed expression of alpha-synuclein, the first gene identified to contribute to inherited forms of Parkinson disease (PD), in the dopaminergic neurons (DA) of flies has provided a robust and well studied Drosophila model of PD complete with the loss of neurons and accompanying motor defects. To more fully understand the biological basis of Bcl-2 genes in PD, we altered the expression of Buffy in the dopamine producing neurons with and without the expression of alpha-synuclein, and in the developing neuron-rich eye. RESULTS: To alter the expression of Buffy in the dopaminergic neurons of Drosophila, the Ddc-Gal4 transgene was used. The directed expression of Buffy in the dopamine producing neurons resulted in flies with increased climbing ability and enhanced survival, while the inhibition of Buffy in the dopaminergic neurons reduced climbing ability over time prematurely, similar to the phenotype observed in the alpha-synuclein-induced Drosophila model of PD. Subsequently, the expression of Buffy was altered in the alpha-synuclein-induced Drosophila model of PD. Analysis revealed that Buffy acted to rescue the associated loss of locomotor ability observed in the alpha-synuclein-induced model of PD, while Buffy RNA interference resulted in an enhanced alpha-synuclein-induced loss of climbing ability. In complementary experiments the overexpression of Buffy in the developing eye suppressed the mild rough eye phenotype that results from Gal4 expression and from alpha-synuclein expression. When Buffy is inhibited the roughened eye phenotype is enhanced. CONCLUSIONS: The inhibition of Buffy in DA neurons produces a novel model of PD in Drosophila. The directed expression of Buffy in DA neurons provide protection and counteracts the alpha-synuclein induced Parkinson disease-like phenotypes. Taken all together this demonstrates a role for Buffy, a Bcl-2 pro-cell survival gene, in neuroprotection. PMID- 27192976 TI - Positive geotactic behaviors induced by geomagnetic field in Drosophila. AB - BACKGROUND: Appropriate vertical movement is critical for the survival of flying animals. Although negative geotaxis (moving away from Earth) driven by gravity has been extensively studied, much less is understood concerning a static regulatory mechanism for inducing positive geotaxis (moving toward Earth). RESULTS: Using Drosophila melanogaster as a model organism, we showed that geomagnetic field (GMF) induces positive geotaxis and antagonizes negative gravitaxis. Remarkably, GMF acts as a sensory cue for an appetite-driven associative learning behavior through the GMF-induced positive geotaxis. This GMF induced positive geotaxis requires the three geotaxis genes, such as cry, pyx and pdf, and the corresponding neurons residing in Johnston's organ of the fly's antennae. CONCLUSIONS: These findings provide a novel concept with the neurogenetic basis on the regulation of vertical movement by GMF in the flying animals. PMID- 27192977 TI - Rescue of dnapol-null Autographa californica multiple nucleopolyhedrovirus with DNA polymerase (DNApol) of Spodoptera litura nucleopolyhedrovirus (SpltNPV) and identification of a nuclear localization signal in SpltNPV DNApol. AB - DNA polymerase (DNApol) is highly conserved in all baculoviruses and plays an essential role in viral DNA replication. It determines the fidelity of baculovirus DNA replication by inserting the correct nucleotides into the primer terminus and proofreading any mispaired nucleotides. DNApols of groups I and II of the genus Alphabaculovirus in the family Baculoviridae share many common structural features. However, it is not clear whether a group I Autographa californica multiple nucleopolyhedrovirus (AcMNPV) DNApol can be substituted by a group II NPV DNApol. Here we report the successful generation of AcMNPV dnapol null virus being rescued by a group II Spodoptera litura NPV (SpltNPV) dnapol (Bac-AcDeltaPol : Slpol). Viral growth curves and quantitative real-time PCR showed that the dnapol replacement reduced the level of viral production and DNA replication of Bac-AcDeltaPol : SlPol compared with WTrep, a native dnapol insertion in an AcMNPV dnapol-null virus. Light microscopy showed that production of occlusion bodies for Bac-AcDeltaPol : Slpol was reduced. We also identified a nuclear localization signal (NLS) for the SpltNPV DNApol C terminus at residues 827-838 by mutational analysis and confocal microscopy. Multiple point substitution of SpltNPV DNApol NLS abrogated virus production and viral DNA replication. Overall, these data suggested that the NLS plays an important role in SpltNPV DNApol nuclear localization and that SpltNPV DNApol cannot efficiently substitute the AcMNPV DNApol in AcMNPV. PMID- 27192978 TI - Protein expression changes induced in a malignant melanoma cell line by the curcumin analogue compound D6. AB - BACKGROUND: We have previously demonstrated that the hydroxylated biphenyl compound D6 (3E,3'E)-4,4'-(5,5',6,6'-tetramethoxy-[1,1'-biphenyl]-3,3' diyl)bis(but-3-en-2-one), a structural analogue of curcumin, exerts a strong antitumor activity on melanoma cells both in vitro and in vivo. Although the mechanism of action of D6 is yet to be clarified, this compound is thought to inhibit cancer cell growth by arresting the cell cycle in G2/M phase, and to induce apoptosis through the mitochondrial intrinsic pathway. To investigate the changes in protein expression induced by exposure of melanoma cells to D6, a differential proteomic study was carried out on D6-treated and untreated primary melanoma LB24Dagi cells. METHODS: Proteins were fractionated by SDS-PAGE and subjected to in gel digestion. The peptide mixtures were analyzed by liquid chromatography coupled with tandem mass spectrometry. Proteins were identified and quantified using database search and spectral counting. Proteomic data were finally uploaded into the Ingenuity Pathway Analysis software to find significantly modulated networks and pathways. RESULTS: Analysis of the differentially expressed protein profiles revealed the activation of a strong cellular stress response, with overexpression of several HSPs and stimulation of ubiquitin-proteasome pathways. These were accompanied by a decrease of protein synthesis, evidenced by downregulation of proteins involved in mRNA processing and translation. These findings are consistent with our previous results on gene expression profiling in melanoma cells treated with D6. CONCLUSIONS: Our findings confirm that the curcumin analogue D6 triggers a strong stress response in melanoma cells, turning down majority of cell functions and finally driving cells to apoptosis. PMID- 27192979 TI - Triglycerides are a predictive factor for arterial stiffness: a community-based 4.8-year prospective study. AB - BACKGROUND: Epidemiological studies have disclosed an independent effect of triglycerides on coronary heart disease despite achievement of low-density lipoprotein cholesterol goals with statin therapy. Arterial stiffness has been increasingly recognized as a strong predictor of cardiovascular disease and atherosclerotic disease. The association between triglycerides and arterial stiffness is not well characterized. We aimed to determine the relationship between triglycerides and arterial stiffness in a community-based longitudinal sample from Beijing, China. METHODS: We related levels of plasma TGs to measures of arterial stiffness (carotid-femoral pulse wave velocity [PWV] and carotid radial PWV) in 1447 subjects (mean age, 61.3 years) from a community-based population in Beijing, China. RESULTS: After a median follow-up interval of 4.8 years, multiple linear regression analysis revealed that TGs were independently associated with carotid-femoral PWV (beta = 0.747, P < 0.001) and carotid-radial PWV (beta = 0.367, P = 0.001). In the group older than 65 years, the association between baseline TG levels and follow-up carotid-femoral PWV (beta = 1.094, P = 0.001) and carotid-radial PWV (beta = 0.524, P = 0.002) were strengthened. In forward stepwise multivariate logistic regression analysis, every SD increase in TGdelta was associated with a 1.296-increased likelihood of the presence of carotid-femoral PWVdeltaII (OR [per SD increase in TGdelta]: 1.296; 95% CI: 1.064 ~ 1.580; P = 0.010) in Model 2, whereas the relationship between TGdelta and carotid-radial PWVdeltaII disappeared. In addition, the relationship was strengthened between TGdelta and the presence of carotid-femoral PWVdeltaII (OR 1.526, 95% CI: 1.088-2.141, P = 0.014) in the group older than 65 years but not carotid-radial PWVdeltaII. No association was noted in subjects younger than 65 years. CONCLUSIONS: Lower triglyceride levels were significantly associated with decreases in carotid-femoral PWV, indicating that achieving low TG levels may be an additional therapeutic consideration in subjects with atherosclerotic disease. PMID- 27192981 TI - Radiologic anatomy of the maxillary artery in the pterygopalatine area applied to Le Fort 1 osteotomies. AB - PURPOSE: In Le Fort 1 osteotomies there is a risk of injuring the maxillary artery, during the pterygomaxillary (PM) disjunction. To improve the knowledge of the relation between the maxillary artery and the PM suture, an anatomic study of the pterygopalatal fossa has been performed. METHODS: The study was based on CT scan head with vascular injection of the supraaortic trunks in 92 patients. The vertical length of the PM junction and the position of maxillary artery in relation to PM junction have been measured on a parasagittal plane passing through the lateral surface of the PM junction, and on a plane where the PM suture is the highest. RESULTS: The height of the PM junction on the plane passing through the lateral surface of the PM junction was 6.86 +/- 2.67 mm, and the maxillary artery was located 18.22 +/- 3.79 mm from the most inferior point of the PM junction. The maximum PM junction height was 13.96 +/- 3.03 mm, and at this place the maxillary artery was located 18.85 +/- 3.26 mm from the most inferior point of the PM junction. The distance between these two planes was 5.14 +/- 2.02 mm. CONCLUSIONS: According to our results, the height of the PM junction is less than 14 mm and during the PM disjunction there is a risk of injuring the maxillary artery 18 mm above the inferior extremity of the PM junction. PMID- 27192980 TI - A morphometric study of the atlas occipitalization and coexisted congenital anomalies of the vertebrae and posterior cranial fossa with neurological importance. AB - PURPOSE: Our study highlights the morphometry of the partial and complete atlas occipitalization (AOZ), its coexistence with fusions of the 2nd and 3rd cervical vertebrae and morphological and morphometric abnormalities of the posterior cranial fossa that are of paramount neurological importance. METHODS: One hundred and eighty adult dry skulls, the atlas and axis vertebrae were examined. RESULTS: Four skulls (2.2 %) showed AOZ. Two of them (1.1 %) presented a partial AOZ, one male skull (0.6 %) a complete AOZ and a female skull (0.6 %) had a fused left hemiatlas with the occipital bone and a fusion of the 2nd and 3rd cervical vertebrae. The inner anteroposterior and transverse diameters of the foramen magnum (FM) in the control group were 34.6 +/- 3.46 and 29.3 +/- 3.47 mm. Only the skull with the complete AOZ had a reduced outer anteroposterior diameter of the FM (29.8 mm), while no specimen was found with a reduced transverse diameter. A wide total decrease (range 13.1-50.9 %) in the surface area of the FM in skulls with AOZ was detected. Extracranial, the clivus length in two skulls with AOZ was smaller than the normal range. No skull was detected with a reduction in the intracranial length of the clivus. All skulls with the AOZ had a vermian fossa. CONCLUSIONS: The study adds important morphometric details about the partial and complete AOZ and correlates the phenomenon of synostosis with the narrowing of the FM, particularly in the case of complete AOZ. Awareness of the AOZ and other fusions of the upper cervical vertebrae and their topographical relations and attendant problems are of paramount importance to surgeons, when operate to the craniocervical junction, or interpret imaging studies to plan a safe surgery for nerve or spinal tissue decompression. PMID- 27192982 TI - Low radiation dose computed tomography coronary angiography: evaluation of the variations in coronary arteries. AB - OBJECTIVE: Despite attempts to decrease the radiation dose, coronary computed tomography angiography (CCTA) generally uses higher doses than computed tomography scans of other organs. The purpose of this study was to evaluate the incidence of the variations of the coronary arteries using the adaptive statistical iterative reconstruction technique to perform low-dose coronary computed tomography (CTA). METHODS: Diagnostic CCTA scans were performed in 3433 patients (from November 2010 to January 2015) using an Optima CT660 (GE Healthcare, USA) 64-slice and analyzed retrospectively. RESULTS: The mean effective dose was 2.1 mSv (1.2-4.9 mSv) for prospective and 4.5 mSv (3.6-9.1 mSv) for retrospective ECG-gated scans. The variations of the coronary arteries (CA) excluding myocardial bridge (MB) were detected in 76 (2.2 %) of the 3433 patients. A myocardial bridge was the most common variation (n = 288, 8.3 %). The second most common variation (n = 13, 17.1 %) was an absence of the left main coronary artery (LMCA) with separate starting points for the left anterior descending (LAD) and left circumflex (LCX) arteries. In addition, there was a rare variation (n = 1, 1.3 %) consisting of the LAD artery originating from the right coronary artery (RCA). CONCLUSIONS: The present retrospective study was conducted using CCTA on patients with a coronary artery variations in Turkey (n = 3433). Our data show that low-dose CCTA can be used to detect common coronary variations. PMID- 27192983 TI - Usefulness of three-dimensional computed tomographic anatomy in endoscopic frontal recess surgery. AB - PURPOSE: The endoscopic bidimensional vision offered by the endoscope during endoscopic sinus surgery involves difficulty in visualizing surgical field depth which makes it difficult to learn this surgical technique and makes it necessary for the endoscopic surgeon to mentally create a three-dimensional (3D) picture of the paranasal sinuses anatomy. In particular, frontal recess surgery requires good knowledge of its anatomic position, also since it is necessary to use angled endoscopes, which distort the view, and angular instruments which are difficult to use. Purpose of this project is to offer to the endoscopic surgeon a detailed 3D model of the nose and paranasal sinuses with particular attention to the frontal recess. METHODS: A 3D reconstruction of the frontal recess and its related structures, starting from computer tomography scans of the human skull, was realized using a professional 3D graphics software. RESULTS: A detailed reconstruction of the main structures which contribute to form the frontal recess was obtained. Particular attention was paid when reproducing the agger nasi cells, uncinate process, ethmoidal bulla, anterior ethmoidal cells, frontoethmoidal cells and their anatomic variants. CONCLUSIONS: This is the first experience reported in literature regarding this new technique of iconographic didactics applied to endoscopic sinus surgery. It represents a new frontier, which surpasses and integrates the previous didactic techniques to help the surgeon to mentally create a 3D image of the paranasal sinuses. PMID- 27192984 TI - Is Cerebellar Architecture Shaped by Sensory Ecology in the New Zealand Kiwi (Apteryx mantelli). AB - Among some mammals and birds, the cerebellar architecture appears to be adapted to the animal's ecological niche, particularly their sensory ecology and behavior. This relationship is, however, not well understood. To explore this, we examined the expression of zebrin II (ZII) in the cerebellum of the kiwi (Apteryx mantelli), a fully nocturnal bird with auditory, tactile, and olfactory specializations and a reduced visual system. We predicted that the cerebellar architecture, particularly those regions receiving visual inputs and those that receive trigeminal afferents from their beak, would be modified in accordance with their unique way of life. The general stripe-and-transverse region architecture characteristic of birds is present in kiwi, with some differences. Folium IXcd was characterized by large ZII-positive stripes and all Purkinje cells in the flocculus were ZII positive, features that resemble those of small mammals and suggest a visual ecology unlike that of other birds. The central region in kiwi appeared reduced or modified, with folium IV containing ZII+/- stripes, unlike that of most birds, but similar to that of Chilean tinamous. It is possible that a reduced visual system has contributed to a small central region, although increased trigeminal input and flightlessness have undoubtedly played a role in shaping its architecture. Overall, like in mammals, the cerebellar architecture in kiwi and other birds may be substantially modified to serve a particular ecological niche, although we still require a larger comparative data set to fully understand this relationship. PMID- 27192986 TI - Lipopolysaccharide-Induced Behavioral Alterations Are Alleviated by Sodium Phenylbutyrate via Attenuation of Oxidative Stress and Neuroinflammatory Cascade. AB - Oxido-nitrosative stress, neuroinflammation, and reduced level of neurotrophins are implicated in the pathophysiology of anxiety and depressive illness. A few recent studies have revealed the role of endoplasmic reticulum (ER) stress in the pathophysiology of stress and depression. The aim of the present study is to investigate the neuroprotective potential of sodium phenylbutyrate (SPB), an ER stress inhibitor against lipopolysaccharide (LPS)-induced anxiety and depressive like behavior in Swiss albino mice. Anxiety and depressive-like behavior was induced by LPS (0.83 mg/kg; i.p.) administration. Various behavioral tests were conducted to evaluate the anxiety and depressive-like behavior in mice. Real-time PCR was employed for the detection and expression of ER stress markers (78-kDa glucose-regulated protein (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP)). Pretreatment with SPB significantly ameliorated the LPS-induced anxiety and depressive-like behavior as revealed by behavioral paradigm results. LPS-induced oxidative stress was ameliorated by SPB pretreatment in hippocampus (HC) and prefrontal cortex (PFC) region. Neuroinflammation was significantly reduced by SPB pretreatment in LPS-treated mice as evident from reduction in proinflammatory cytokines (IL-1beta and TNF-alpha). Importantly, LPS administration significantly up-regulated the GRP78 mRNA expression level in the HC which suggests the involvement of unfolded protein response (UPR) in LPS evoked behavioral anomalies. These results highlight the neuroprotective potential of SPB in LPS-induced anxiety and depressive illness model which may be partially due to inhibition of oxidative stress-neuroinflammatory cascade. PMID- 27192988 TI - Electronic Patient Records to Identify Patients in the United Kingdom with Diabetic Macular Oedema Suitable for ILUVIEN((r)) (Fluocinolone Acetonide). AB - INTRODUCTION: We describe a proactive method using electronic patient records (EPR) to identify pseudophakic patients with diabetic macular oedema (DMO) that might benefit from treatment with 0.2 ug/day fluocinolone acetonide (FAc; ILUVIEN((r))) implant. METHODS: Our EPR audit tool (Medisoft((r))) identified diabetic patients (May 2011-December 2014) with National Screening Committee confirmed grade M1 maculopathy. Searches segmented this DMO patient population into patient groups who: (1) had received ranibizumab therapy, (2) had received >=2 macular laser treatments, or (3) were unsuitable for macular laser or ranibizumab therapy. Pre-specified criteria identified patients insufficiently responsive to treatment, and their electronic case notes were flagged for clinicians to consider FAc, based on National Institute for Health and Care Excellence (NICE) TA301. RESULTS: Using this methodology, 138 patients with DMO were identified, of whom 87 were assigned to group 1, 32 to group 2, and 29 to group 3 (10 patients were included in both groups 2 and 3). From these, 28 different pseudophakic eyes were identified as suitable for treatment with FAc, based on insufficient response to prior treatment. CONCLUSION: EPR audit offers a real-world methodology to efficiently identify patients that might benefit from treatment with FAc. Limitations apply, and thorough documentation of lens status and ocular comorbidities is vital; however, this approach was more rapid than prospective recruitment through the clinic. Flagging patient records using EPR audit offers a practical process for application to clinical practice, thereby optimizing patient care in line with NICE TA301 guidelines. FUNDING: Alimera Sciences Ltd. PMID- 27192985 TI - NB-3 signaling mediates the cross-talk between post-traumatic spinal axons and scar-forming cells. AB - Little is known about the molecules mediating the cross-talk between post traumatic axons and scar-forming cells after spinal cord injury. We found that a sustained NB-3 induction was simultaneously present in the terminations of post traumatic corticospinal axons and scar-forming cells at the spinal lesion site, where they were in direct contact when axons tried to penetrate the glial scar. The regrowth of corticospinal axons was enhanced in vivo with NB-3 deficiency or interruption of NB-3 trans-homophilic interactions. Biochemical, in vitro and in vivo evidence demonstrated that NB-3 homophilically interacted in trans to initiate a growth inhibitory signal transduction from scar-forming cells to neurons by modulating mTOR activity via CHL1 and PTPsigma. NB-3 deficiency promoted BMS scores, electrophysiological transmission, and synapse reformation between regenerative axons and neurons. Our findings demonstrate that NB-3 trans homophilic interactions mediate the cross-talk between post-traumatic axons and scar-forming cells and impair the intrinsic growth ability of injured axons. PMID- 27192987 TI - Selenium Pretreatment for Mitigation of Ischemia/Reperfusion Injury in Cardiovascular Surgery: Influence on Acute Organ Damage and Inflammatory Response. AB - Ischemia/reperfusion injury (IRI) contributes to morbidity and mortality after cardiovascular surgery requiring cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA). Multi-organ damage is associated with substantial decreases of blood selenium (Se) levels in patients undergoing cardiac surgery with CPB. We compared the influence of a dietary surplus of Se and pretreatment with ebselen, a mimic of the selenoenzyme glutathione peroxidase, on IRI-induced tissue damage and inflammation. Male Wistar rats were fed either a Se-adequate diet containing 0.3 ppm Se or supplemented with 1 ppm Se (as sodium selenite) for 5 weeks. Two other groups of Se-adequate rats received intraperitoneal injection of ebselen (30 mg/kg) or DMSO (solvent control) before surgery. The animals were connected to a heart-lung-machine and underwent 45 min of global ischemia during circulatory arrest at 16 degrees C, followed by re warming and reperfusion. Selenite and ebselen suppressed IRI-induced leukocytosis and the increase in plasma levels of tissue damage markers (AST, ALT, LDH, troponin) during surgery but did not prevent the induction of proinflammatory cytokines (IL-6, TNF-alpha). Both Se compounds affected phosphorylation and expression of proteins related to stress response and inflammation: Ebselen increased phosphorylation of STAT3 transcription factor in the heart and decreased phosphorylation of ERK1/2 MAP kinases in the lungs. Selenite decreased ERK1/2 phosphorylation and HSP-70 expression in the heart. Pretreatment with selenite or ebselen protected against acute IRI-induced tissue damage during CPB and DHCA. Potential implications of their different actions with regard to molecular stress markers on the recovery after surgery represent promising targets for further investigation. PMID- 27192989 TI - Depot-specific effects of treadmill running and rutin on white adipose tissue function in diet-induced obese mice. AB - White adipose tissue (WAT) is a critical organ involved in regulating metabolic homeostasis under obese condition. Strategies that could positively affect WAT function would hold promise for fighting against obesity and its complications. The aim of the present study is to explore the effects of treadmill exercise training and rutin intervention on adipose tissue function from diet-induced obese (DIO) mice and whether fat depot-specific effects existed. In epididymal adipose tissue, high-fat diet (HFD) resulted in reduction in adiponectin mRNA expression, peroxisome proliferator-activated receptors (PPAR)-gamma and DsbA-L protein expression, elevation in endoplasmic reticulum (ER) stress markers including 78 kDa glucose-regulated protein (GRP-78), C/EBP homologous protein (CHOP) and p-c-Jun N-terminal kinase (JNK). Isoproterenol-stimulated lipolysis and insulin stimulated Akt phosphorylation ex vivo were blunted from HFD group. The combination of rutin with exercise (HRE) completely restored GRP78 and p-JNK protein expression to normal levels, as well as blunted signaling ex vivo. In inguinal adipose tissue, HFD led to increased adiponectin mRNA expression, PPAR gamma, GRP78, and p-JNK protein expression, and reduction in DsbA-L. HRE is effective for restoring p-JNK, PPAR-gamma, and DsbA-L. In conclusion, depot specific effects may exist in regard to the effects of rutin and exercise on key molecules involved in regulating adipose tissue function (i.e., ER stress markers, PPAR-gamma and DsbA-L, adiponectin expression, and secretion, ex vivo catecholamine stimulated lipolysis and insulin stimulated Akt phosphorylation) from DIO mice. PMID- 27192990 TI - Comparing Length of Stay Between Patients Taking Rivaroxaban and Conventional Anticoagulants for Treatment of Venous Thromboembolism. AB - BACKGROUND: Recent studies have demonstrated non-inferiority of rivaroxaban when compared to warfarin for the treatment of pulmonary embolism and deep venous thrombosis. Analysis of data from the EINSTEIN trials has demonstrated that patients who received rivaroxaban had a shorter length of stay (LOS) compared to those who received warfarin. However, these trials had strict inclusion and exclusion criteria, and were designed for a different primary outcome. Also, data from these closely monitored clinical trials may not reflect the daily practice of medicine. OBJECTIVES: To clarify this issue further, we performed a retrospective analysis at our institution, comparing the LOS between patients discharged on rivaroxaban and other conventional anticoagulants (warfarin, enoxaparin, and enoxaparin with warfarin). METHODS: This was a retrospective study of consecutive patients admitted to our institution from January 2011 to July 2014 with newly diagnosed venous thromboembolism (VTE). Inclusion criteria were age > 18 years and objective confirmation of VTE. Exclusion criteria included diagnosis of VTE 24 h after admission, contraindication to anticoagulation, treatment with fibrinolytic agents, patients already on anticoagulation, and pregnancy. Out of 1553 consecutive patients diagnosed with VTE, a total of 414 patients met the eligibility criteria. These patients were further subdivided into four groups based on their discharge anticoagulant: rivaroxaban, warfarin, enoxaparin, and warfarin with enoxaparin. RESULTS: Patients discharged on rivaroxaban had a significantly shorter LOS compared with patients discharged on warfarin (3.5 vs. 7.0 days; p < 0.001), but not when compared to those discharged on enoxaparin alone (3.0 days) or enoxaparin with warfarin (4.0 days) (p > 0.05). The hospital incidence of bleeding and the 6 month readmission rates were not different among the different anticoagulants. CONCLUSIONS: In patients admitted with newly diagnosed VTE, those discharged on rivaroxaban had a significantly shorter LOS compared to those discharged on warfarin. In the appropriate subset of patients with VTE, treatment with rivaroxaban may result in significant cost savings for the hospital. PMID- 27192991 TI - Pneumolysin Mediates Platelet Activation In Vitro. AB - This study has explored the role of the pneumococcal toxin, pneumolysin (Ply), in activating human platelets. Following exposure to Ply (10-80 ng/ml), platelet activation and cytosolic Ca(2+) concentrations were measured flow cytometrically according to the level of expression of CD62P (P-selectin) and spectrofluorimetrically, respectively. Exposure to Ply resulted in marked upregulation of expression of platelet CD62P, achieving statistical significance at concentrations of 40 ng/ml and higher (P < 0.05), in the setting of increased influx of Ca(2+). These potentially pro-thrombotic actions of Ply were attenuated by depletion of Ca(2+) from the extracellular medium or by exposure of the cells to a pneumolysoid devoid of pore-forming activity. These findings are consistent with a mechanism of Ply-mediated platelet activation involving sub-lytic pore formation, Ca(2+) influx, and mobilization of CD62P-expressing alpha-granules, which, if operative in vivo, may contribute to the pathogenesis of associated acute lung and myocardial injury during invasive pneumococcal disease. PMID- 27192992 TI - Notices and Policies for Retractions, Expressions of Concern, Errata and Corrigenda: Their Importance, Content, and Context. AB - A retraction notice is an essential scientific historical document because it should outline the reason(s) why a scientific manuscript was retracted, culpability (if any) and any other factors that have given reason for the authors, editors, or publisher, to remove a piece of the literature from science's history books. Unlike an expression of concern (EoC), erratum or corrigendum, a retraction will usually result in a rudimentary vestige of the work. Thus, any retraction notice that does not fully indicate a set of elements related to the reason and background for the retraction serves as a poor historical document. Moreover, poorly or incompletely worded retraction notices in fact do not serve their intended purpose, i.e., to hold all parties accountable, and to inform the scientific and wider public of the problem and reason for the paper's demise. This paper takes a look at the definitions and the policies of clauses for retractions, EoCs, errata and corrigenda in place by 15 leading science, technology and medicine (STM) publishers and four publishing related bodies that we believe have the greatest influence on the current fields of science, technology and medicine. The primary purpose was to assess whether there is a consistency among these entities and publishers. Using an arbitrary 5 scale classification system, and evaluating the different categories of policies separately, we discovered that in almost all cases (88.9 %), the wording used to define these four categories of polices differs from that of the Committee on Publication Ethics (COPE), which is generally considered to be the guiding set of definitions in science publishing. In addition, as much as 61 % deviation in policies (wording and meaning), relative to COPE guidelines, was discovered. When considering the average pooled deviation across all categories of policies, we discovered that there was either no deviation or a small deviation, only in the wording, in the definition of policies when compared to the COPE guidelines in 1 out of 3 ethical bodies, and in 40 % (6 out of 15) STM publishers. Moderate deviation from the COPE guidelines was detected in 26.7 % of STM publishers and one ethical body but a large deviation in one ethical body and 20 % of STM publishers was observed. Two STM publishers (13.3 %) did not report any information about these policies. Even though in practice, editors and publishers may deviate from these written definitions when dealing with case-by-case issues, we believe that it is essential, to serve as a consistent guide for authors and editors, that the wording be standardized across these entities. COPE and these entities also have the responsibility of making it clear that these definitions are merely suggestions and that their application may be subjected to subjective interpretation and application. PMID- 27192993 TI - Risk, Uncertainty and Precaution in Science: The Threshold of the Toxicological Concern Approach in Food Toxicology. AB - Environmental risk assessment is often affected by severe uncertainty. The frequently invoked precautionary principle helps to guide risk assessment and decision-making in the face of scientific uncertainty. In many contexts, however, uncertainties play a role not only in the application of scientific models but also in their development. Building on recent literature in the philosophy of science, this paper argues that precaution should be exercised at the stage when tools for risk assessment are developed as well as when they are used to inform decision-making. The relevance and consequences of this claim are discussed in the context of the threshold of the toxicological concern approach in food toxicology. I conclude that the approach does not meet the standards of an epistemic version of the precautionary principle. PMID- 27192994 TI - When is it time to move to the next map? Optimal foraging in guided visual search. AB - Suppose that you are looking for visual targets in a set of images, each containing an unknown number of targets. How do you perform that search, and how do you decide when to move from the current image to the next? Optimal foraging theory predicts that foragers should leave the current image when the expected value from staying falls below the expected value from leaving. Here, we describe how to apply these models to more complex tasks, like search for objects in natural scenes where people have prior beliefs about the number and locations of targets in each image, and search is guided by target features and scene context. We model these factors in a guided search task and predict the optimal time to quit search. The data come from a satellite image search task. Participants searched for small gas stations in large satellite images. We model quitting times with a Bayesian model that incorporates prior beliefs about the number of targets in each map, average search efficiency (guidance), and actual search history in the image. Clicks deploying local magnification were used as surrogates for deployments of attention and, thus, for time. Leaving times (measured in mouse clicks) were well-predicted by the model. People terminated search when their expected rate of target collection fell to the average rate for the task. Apparently, people follow a rate-optimizing strategy in this task and use both their prior knowledge and search history in the image to decide when to quit searching. PMID- 27192995 TI - Working memory-driven attention improves spatial resolution: Support for perceptual enhancement. AB - Previous research has indicated that attention can be biased toward those stimuli matching the contents of working memory and thereby facilitates visual processing at the location of the memory-matching stimuli. However, whether this working memory-driven attentional modulation takes place on early perceptual processes remains unclear. Our present results showed that working memory-driven attention improved identification of a brief Landolt target presented alone in the visual field. Because the suprathreshold target appeared without any external noise added (i.e., no distractors or masks), the results suggest that working memory driven attention enhances the target signal at early perceptual stages of visual processing. Furthermore, given that performance in the Landolt target identification task indexes spatial resolution, this attentional facilitation indicates that working memory-driven attention can boost early perceptual processing via enhancement of spatial resolution at the attended location. PMID- 27192996 TI - Which long-term antiplatelet regimen for patients with acute coronary syndromes? AB - Dual antiplatelet therapy (DAPT ) is recommended up to 12 months in patients with acute coronary syndromes, but the risk of cardiovascular events in this group of subjects remains high, also in the long-term follow-up. The potential benefit of a prolonged period of DAPT has recently been assessed in three large-volume randomized clinical trials (PEGASUS, DAPT-MI, TRA2P-TIMI 50) but final results are quite difficult to interpret and clear indications for the clinical practice are so far lacking. A direct comparison of the three studies is challenging since relevant differences exist as to clinical features and risk profile of the study populations. Different anti-platelet drugs have been tested in addition to aspirin making it difficult to understand which antithrombotic regimen guarantees the best balance between thrombotic and haemorragic events. Finally, specific designs of these trials, evaluating complex composite end-points, may generate further difficulties in the interpretation of data. We believe that the use of total mortality rather than cardiovascular death as end-point, would better describe the long-term outcome incorporating the catastrophic consequences of bleeding. This review seeks to highlight strengths and weaknesses of these three large-volume trials and tries to establish whether or not prolonging DAPT beyond 12 months in patients with acute coronary syndromes is useful and which anti thrombotic regimen would offer the best balance between thrombotic and bleeding risk. PMID- 27192997 TI - Impact of shade on outdoor thermal comfort-a seasonal field study in Tempe, Arizona. AB - Shade plays an important role in designing pedestrian-friendly outdoor spaces in hot desert cities. This study investigates the impact of photovoltaic canopy shade and tree shade on thermal comfort through meteorological observations and field surveys at a pedestrian mall on Arizona State University's Tempe campus. During the course of 1 year, on selected clear calm days representative of each season, we conducted hourly meteorological transects from 7:00 a.m. to 6:00 p.m. and surveyed 1284 people about their thermal perception, comfort, and preferences. Shade lowered thermal sensation votes by approximately 1 point on a semantic differential 9-point scale, increasing thermal comfort in all seasons except winter. Shade type (tree or solar canopy) did not significantly impact perceived comfort, suggesting that artificial and natural shades are equally efficient in hot dry climates. Globe temperature explained 51 % of the variance in thermal sensation votes and was the only statistically significant meteorological predictor. Important non-meteorological factors included adaptation, thermal comfort vote, thermal preference, gender, season, and time of day. A regression of subjective thermal sensation on physiological equivalent temperature yielded a neutral temperature of 28.6 degrees C. The acceptable comfort range was 19.1 degrees C-38.1 degrees C with a preferred temperature of 20.8 degrees C. Respondents exposed to above neutral temperature felt more comfortable if they had been in air-conditioning 5 min prior to the survey, indicating a lagged response to outdoor conditions. Our study highlights the importance of active solar access management in hot urban areas to reduce thermal stress. PMID- 27192998 TI - Dissipation of excess excitation energy of the needle leaves in Pinus trees during cold winters. AB - Photooxidative damage to the needle leaves of evergreen trees results from the absorption of excess excitation energy. Efficient dissipation of this energy is essential to prevent photodamage. In this study, we determined the fluorescence transients, absorption spectra, chlorophyll contents, chlorophyll a/b ratios, and relative membrane permeabilities of needle leaves of Pinus koraiensis, Pinus tabulaeformis, and Pinus armandi in both cold winter and summer. We observed a dramatic decrease in the maximum fluorescence (F m) and substantial absorption of light energy in winter leaves of all three species. The F m decline was not correlated with a decrease in light absorption or with changes in chlorophyll content and chlorophyll a/b ratio. The results suggested that the winter leaves dissipated a large amount of excess energy as heat. Because the cold winter leaves had lost normal physiological function, the heat dissipation depended solely on changes in the photosystem II supercomplex rather than the xanthophyll cycle. These findings imply that more attention should be paid to heat dissipation via changes in the photosystem complex structure during the growing season. PMID- 27193000 TI - Seasonal Variability May Affect Microbial Decomposers and Leaf Decomposition More Than Warming in Streams. AB - Ongoing climate change is expected to affect the diversity and activity of aquatic microbes, which play a key role in plant litter decomposition in forest streams. We used a before-after control-impact (BACI) design to study the effects of warming on a forest stream reach. The stream reach was divided by a longitudinal barrier, and during 1 year (ambient year) both stream halves were at ambient temperature, while in the second year (warmed year) the temperature in one stream half was increased by ca. 3 degrees C above ambient temperature (experimental half). Fine-mesh bags containing oak (Quercus robur L.) leaves were immersed in both stream halves for up to 60 days in spring and autumn of the ambient and warmed years. We assessed leaf-associated microbial diversity by denaturing gradient gel electrophoresis and identification of fungal conidial morphotypes and microbial activity by quantifying leaf mass loss and productivity of fungi and bacteria. In the ambient year, no differences were found in leaf decomposition rates and microbial productivities either between seasons or stream halves. In the warmed year, phosphorus concentration in the stream water, leaf decomposition rates, and productivity of bacteria were higher in spring than in autumn. They did not differ between stream halves, except for leaf decomposition, which was higher in the experimental half in spring. Fungal and bacterial communities differed between seasons in both years. Seasonal changes in stream water variables had a greater impact on the activity and diversity of microbial decomposers than a warming regime simulating a predicted global warming scenario. PMID- 27192999 TI - Resources of dark skies in German climatic health resorts. AB - Illumination of nocturnal environments is increasing steadily worldwide. While there are some benefits for mankind, light at night affects animals, plants, and human health by blurring the natural distinction between day and night. International regulations exist to protect the environment for the maintenance of human health but nocturnal darkness is not considered. In Germany, cities and communities labeled as Climatic Health Resorts provide for high standards in air quality. However, their degree of nocturnal darkness is unexplored so far. In our study, we examined the degree of nocturnal darkness in German Climatic Health Resorts by two datasets based on georeferenced remote sensing data. The majority of Climatic Health Resorts (93.1 %) are able to offer a relative respite (>= 20 mag/arcsec2) from a degraded nocturnal environment, while only 3.4 % are able to offer a dark, if by no means pristine, night environment (>= 21 mag/arcsec2). Climatic Health Resorts emit less light as well as are less affected by night sky brightness compared to the average of non-classified communities. In combination with daytime requirements, the resorts provide conditions for a more distinct day and-night-cycle than non-classified communities. PMID- 27193001 TI - Competitive Survival of Escherichia coli, Vibrio cholerae, Salmonella typhimurium and Shigella dysenteriae in Riverbed Sediments. AB - Studies on the survival of bacterial enteric pathogens in riverbed sediments have mostly focused on individual organisms. Reports on the competitive survival of these pathogens in riverbed sediments under the same experimental setup are limited. We investigated the survival of Escherichia coli, Salmonella enterica ser. Typhimurium, Vibrio cholerae and Shigella dysenteriae in riverbed sediments of the Apies River. Experiments were performed in flow chambers containing three sediment types and connected to aquarium pumps immersed in river water to maintain continuous water circulation. Each chamber was inoculated with ~107 CFU/mL (final concentration) of each microorganism and kept at 4, 20 and 30 degrees C. Chambers were sampled on days 0, 1, 2, 7, 14 and 28. At 4 degrees C, only E. coli and S. typhimurium survived throughout the 28 experimental days. V. cholerae had the shortest survival time at this temperature and was not detected in any of the sediment chambers 24 h after inoculation. S. dysenteriae only survived until day 7. At an increased temperature of 20 degrees C, only S. dysenteriae was not detected on day 28 of the experiment. At 30 degrees C, V. cholerae and Salmonella survived longer (28 days) than E. coli (14 days) and S. dysenteriae (4 days). Vibrio cholerae was shown to have the highest T 90 values (32 days) in all sediment types at 20 and 30 degrees C. We conclude that the sediments of the Apies River present a favourable environment for the survival of indicator and pathogenic bacteria depending on the prevailing temperature. PMID- 27193002 TI - Hot Melt Extrusion for Sustained Protein Release: Matrix Erosion and In Vitro Release of PLGA-Based Implants. AB - The design of biodegradable implants for sustained release of proteins is a complex challenge optimizing protein polymer interaction in combination with a mini-scale process which is predictive for production. The process of hot melt extrusion (HME) was therefore conducted on 5- and 9-mm mini-scale twin screw extruders. Poly(lactic-co-glycolic acid) (PLGA) implants were characterized for their erosion properties and the in vitro release of the embedded protein (bovine serum albumin, BSA). The release of acidic monomers as well as other parameters (pH value, mass loss) during 16 weeks indicated a delayed onset of matrix erosion in week 3. BSA-loaded implants released 17.0% glycolic and 5.9% lactic acid after a 2-week lag time. Following a low burst release (3.7% BSA), sustained protein release started in week 4. Storage under stress conditions (30 degrees C, 75% rH) revealed a shift of erosion onset of 1 week (BSA-loaded implants: 26.9% glycolic and 9.3% lactic acid). Coherent with the changed erosion profiles, an influence on the protein release was observed. Confocal laser scanning and Raman microscopy showed a homogenous protein distribution throughout the matrix after extrusion and during release studies. Raman spectra indicated a conformational change of the protein structure which could be one reason for incomplete protein release. The study underlined the suitability of the HME process to obtain a solid dispersion of protein inside a polymeric matrix providing sustained protein release. However, the incomplete protein release and the impact by storage conditions require thorough characterization and understanding of erosion and release mechanisms. PMID- 27193003 TI - Practical Considerations for Determination of Glass Transition Temperature of a Maximally Freeze Concentrated Solution. AB - Glass transition temperature is a unique thermal characteristic of amorphous systems and is associated with changes in physical properties such as heat capacity, viscosity, electrical resistance, and molecular mobility. Glass transition temperature for amorphous solids is referred as (T g), whereas for maximally freeze concentrated solution, the notation is (T g'). This article is focused on the factors affecting determination of T g' for application to lyophilization process design and frozen storage stability. Also, this review provides a perspective on use of various types of solutes in protein formulation and their effect on T g'. Although various analytical techniques are used for determination of T g' based on the changes in physical properties associated with glass transition, the differential scanning calorimetry (DSC) is the most commonly used technique. In this article, an overview of DSC technique is provided along with brief discussion on the alternate analytical techniques for T g' determination. Additionally, challenges associated with T g' determination, using DSC for protein formulations, are discussed. The purpose of this review is to provide a practical industry perspective on determination of T g' for protein formulations as it relates to design and development of lyophilization process and/or for frozen storage; however, a comprehensive review of glass transition temperature (T g, T g'), in general, is outside the scope of this work. PMID- 27193004 TI - An umbilical surprise: a collective review on umbilical pilonidal sinus : An uncommon alternative diagnosis in common umbilical symptoms. AB - PURPOSE: Umbilical pilonidal sinus (UPS) has an atypical clinical presentation and is therefore not well recognized. The aim of this case series and review of the literature, is to provide more insight in the underlying pathology and a guidance for the treatment of this condition. METHODS: Three recent clinical cases are described that made us perform a multi-database research was to reveal relevant literature. RESULTS: Three relevant clinical cases from our clinic are described. Thirth three studies, describing 463 patients were included. Most studies were case reports or series; few were case series or cohort studies. UPS develops by loose hairs getting caught in the umbilical pit and subsequently penetrate the umbilical cicatrix by friction. In this way an inflammatory response is triggered, resulting in oedema that further narrows the umbilical orifice, hence forming a sinus. Several risk factors are identified. There is no particular consensus on the treatment of this disease. Although older literature advocates immediate umbilical excision without exception, recent studies provide evidence that supports multiple courses of conservative treatment. Several cases were described in which surgery consisted of excision of the sinus and hair tufts in contrast to excision of the entire umbilicus. CONCLUSIONS: Umbilical pilonidal disease has an atypical presentation and might mimic conditions such as incarcerated hernia, Anterior Cutaneous Nerve Entrapment Syndrome or urachal cyst. Risk factors that can bring physicians closer to a reliable diagnosis are identified. An example of a treatment algorithm is provided, suggesting surgery should only be considered when conservative treatment fails. PMID- 27193005 TI - [Rational antibiotic treatment of mediastinitis]. AB - Mediastinitis occurs as a severe complication of thoracic and cardiac surgical interventions and is the result of traumatic esophageal perforation, conducted infections or as a result of lymphogenic and hematogenic spread of specific infective pathogens. Treatment must as a rule be accompanied by antibiotics, whereby knowledge of the spectrum of pathogens depending on the pathogenesis is indispensable for successful antibiotic therapy. Polymicrobial infections with a high proportion of anaerobes are found in conducted infections of the mediastinum and after esophageal perforation. After cardiac surgery Staphylococci are the dominant pathogens and a nasal colonization with Staphylococcus aureus seems to be a predisposing risk factor. Fungi are the predominant pathogens in immunocompromised patients with consumptive underlying illnesses and can cause acute or chronic forms with granulomatous inflammation. Resistant pathogens are increasingly being found in high-risk patient cohorts, which must be considered for a calculated therapy. For calculated antibiotic therapy the administration of broad spectrum antibiotics, mostly beta-lactams alone or combined with metronidazole is the therapy of choice for both Gram-positive and Gram-negative bacteria inclusive of anaerobes. For patients at risk, additional antibiotic classes with a spectrum against methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE) can be administered. Increasing rates of multidrug-resistant Gram-negative bacteria (e.g. Enterobacteriaceae) and non-fermenting bacteria (e.g. Pseudomonas and Acinetobacter) in individual cases necessitates the use of polymyxins (e.g. colistin), new tetracyclines (e.g. glycylglycines) and newly developed combinations of beta-lactams and beta-lactam inhibitors. For treatment of fungal infections (e.g. Candida, Aspergillus and Histoplasma) established and novel azoles, amphotericin B and echinocandins seem to be successful; however, detection of Candida, particularly in mixed infections does not always necessitate treatment. Mediastinitis is still a severe infectious disease with a high mortality, which necessitates an early and broad spectrum antibiotic therapy; however, with respect to optimal duration of therapy and selection of antibiotics, data from good quality comparative studies are lacking. PMID- 27193007 TI - Innovative development path of ethnomedicines: an overview of ethnomedicines in China. AB - In the long history of disease prevention and treatment, ancestral populations worldwide have gained knowledge and experiences in traditional medicines. For instance, ethnomedicines of Chinese ethnic minorities constitute an important part of traditional medicines. In our study, we firstly clarified the concept of ethnomedicines and the connotations of ethnopharmacology. The particularity of ethnomedicine research were then summed up, and the development profiles of the ethnomedicines of Chinese ethnic minorities were discussed by investigating the current status and existing problems. On this basis, we abstracted the innovative development path of ethnomedicines for the first time, which was found to follows:resource study -> standardized development research -> industrialization of the achievements and efforts for internationalization. We found that platform establishment and team training are keys to achieving innovative development. Hence, this study provided a basis for ethnomedicine development. PMID- 27193006 TI - [Treatment of chronic mediastinitis]. AB - BACKGROUND: Chronic mediastinitis is a rare disorder characterized by the proliferation of fibrous tissue within the mediastinum resulting in compression of mediastinal structures. OBJECTIVE: This article gives an overview of the treatment options for chronic mediastinitis. MATERIAL AND METHODS: A literature search was carried out regarding treatment options for chronic mediastinitis RESULTS AND CONCLUSION: Little is known about the pathogenesis of chronic mediastinitis, which has hampered the development of novel therapeutic approaches. There is no convincing evidence for the success of medicinal (antifungal or conventional anti-inflammatory) therapy and it is not recommended. In cases of clinical symptoms procedures for decompression, such as endovascular or endobronchial stents or surgical procedures, such as decompression interventions or extra-anatomic bypasses should be considered. The prognosis for unilateral involvement is better than for bilateral involvement if performed in specialized centers. PMID- 27193009 TI - Early OA: point of no return or a chance for regenerative approaches. PMID- 27193008 TI - Preoperative prediction of anterior cruciate ligament tibial footprint size by anthropometric variables. AB - PURPOSE: The purpose of this study was to evaluate whether the ACL tibial footprint size can be predicted by anthropometric variables including height, weight, leg length, femur length, tibia length, and anteroposterior and mediolateral diameters of proximal tibia. METHODS: This study included 209 out of the 378 eligible patients. The inclusion criterion was ACL with normal gross appearance. Patients with conditions that could have affected the measurement were excluded: torn ACL, osteophyte formation around the ACL tibial attachment, presence of inflammatory arthritis, or history of knee joint infection. According to the above criteria, 169 patients were excluded from this study; 138 had torn ACL, 24 had osteophyte around the ACL footprint, 5 had history of rheumatoid arthritis, and 2 had history of previous knee joint infection. The ACL tibial footprint was carefully dissected and measured during total knee arthroplasty. Anthropometric variables regarding bone lengths were measured on radiography. The association of the ACL tibial footprint size (length and width) with anthropometric variables was analysed using simple and multiple linear regression analyses. RESULTS: The height, weight, leg length, femur length, tibia length, and the size of proximal tibia were associated with the ACL tibial footprint length and width. The ACL tibial footprint length could be predicted by the equation using tibia length: ACL tibial footprint length = -9.361 + 0.759 * (tibia length in cm) (R 2 = 0.44, P < 0.001) and width by the equation using weight and tibia length: ACL tibial footprint width = -0.5615 + 0.279 * (tibia length in cm) + 0.0333 * (weight in kgs) (R 2 = 0.17, P < 0.001). The concordance correlation coefficient for the measured and predicted values of ACL tibial footprint length and width showed moderate and low agreement, respectively (0.61, 95 % CI 0.53-0.68; 0.30, 95 % CI 0.21-0.38). CONCLUSION: The ACL tibial footprint length and width are associated with anthropometric variables, especially with tibial length. The predictive equation developed from this study can serve as supplementary guides to determine the surgical techniques and graft options in preoperative planning of an individual ACL reconstruction. LEVEL OF EVIDENCE: IV. PMID- 27193010 TI - Erratum to: Variants in TNIP1, a regulator of the NF-kB pathway, found in two patients with neural tube defects. PMID- 27193011 TI - Reversible striatal hypermetabolism in chorea associated with moyamoya disease: a report of two cases. AB - BACKGROUND: The pathophysiological mechanism of chorea as a presentation of pediatric moyamoya disease remains unknown, although ischemia is suspected as a likely cause. The authors describe two cases of pediatric moyamoya disease, both of which presented with hemichorea in the stable phase after successful bypass surgery. CLINICAL PRESENTATION: Cerebral blood flow was almost normal in one case and decreased in the basal ganglia and watershed area in the other case due to infarcts occurring before surgery. In both cases, 18F-fluorodeoxyglucose positron emission tomography revealed elevated glucose metabolism in the corresponding side of the striatum, which reverted to normal after recovery from chorea. Magnetic resonance angiography revealed a dilated and extended lenticulostriate artery at the exact site of the hypermetabolic lesion. PMID- 27193012 TI - Thinking outside the shunt-sterile CSF malabsorption in pilocytic astrocytomas: case series and review of the literature. AB - INTRODUCTION: Ventriculoperitoneal (VP) shunt insertion is the most common cerebrospinal fluid (CSF) diversionary procedure used for the treatment of chronic hydrocephalus. Sterile CSF ascites is a rare complication of VP shunt insertion. This can arise from either an overproduction of CSF or inadequate filtration of CSF at the level of the peritoneum. By either mechanism, the development of CSF ascites requires an intact VP shunt. OBJECTIVE: The authors discuss two paediatric cases diagnosed with suprasellar pilocytic astrocytomas treated with platinum-based chemotherapy, who subsequently developed sterile CSF ascites. We review the literature with regard to CSF malabsorption and discuss it as a contributing factor to shunt malfunction. CONCLUSION: CSF malabsorption with resultant ascites is a rare complication of VP shunting with many etiologies. Two common predisposing factors included the use of platinum-based chemotherapeutic agents, as well as the specific neuropathology. Further analysis of these two entities is needed in order to elucidate their role in contributing to the development of CSF ascites in this patient cohort. PMID- 27193013 TI - Evaluation and quantitative analysis of different growth periods of herb-arbor intercropping systems using HPLC and UV-vis methods coupled with chemometrics. AB - As a result of the pressure from population explosion, agricultural land resources require further protecting and rationally utilizing. Intercropping technique has been widely applied for agricultural production to save cultivated area, improve crop quality, and promote agriculture economy. In this study, we employed high-performance liquid chromatography (HPLC) and ultraviolet-visible spectroscopy (UV-vis) combined with chemometrics for determination and qualitative evaluation of several kinds of intercropping system with Gentiana rigescens Franch. ex Hemsl. (GR), which is used as an hepatic protector in local communities in China. Results revealed that GR in a Camellia sinensis intercropping system contained most gentiopicroside, sweroside, and total active constituents (six chemical indicators), whose content reached 91.09 +/- 3.54, 1.03 +/- 0.06, and 104.05 +/- 6.48 mg g(-1), respectively. The two applied quantitative and qualitative methods reciprocally verified that GR with 2 years of growth period performed better in terms of quality than 1 year, collectively. PMID- 27193014 TI - Anti-dormant mycobacterial activity and target molecule of melophlins, tetramic acid derivatives isolated from a marine sponge of Melophlus sp. AB - Tuberculosis (TB), caused by Mycobacterium tuberculosis infection, is a major world health problem that is responsible for the deaths of 1.5 million people each year. In addition, the requirement for long-term therapy to cure TB complicates treatment of the disease. One of the major reasons for the extended chemotherapeutic regimens and wide epidemicity of TB is that M. tuberculosis has the ability to persist in a dormant state. We therefore established a new screening system to search for substances with activity against dormant mycobacteria using M. smegmatis and M. bovis BCG cultivated in medium containing propionate as sole carbon source to induce dormancy. Subsequently, melophlins A (1), G (2), H (3), and I (4), tetramic acid derivatives, were re-discovered from the Indonesian marine sponge of Melophlus sp. as anti-dormant mycobacterial substances. Moreover, target analysis of melophlin A indicated that it targeted the BCG1083 protein of putative exopolyphosphatase and the BCG1321c protein of diadenosine 5',5'''-P(1),P(4)-tetraphosphate phosphorylase. PMID- 27193015 TI - Erratum to: An Invariant-Based Damage Model for Human and Animal Skins. PMID- 27193016 TI - Estimation of a physician practice cost function. AB - OBJECTIVE: The goal of the present paper is to provide evidence on the behavior of physician practice cost functions. DATA SOURCES: Our study is based on the data of 3686 physician practices in Germany for the years 2006 to 2008. STUDY DESIGN: We apply a translog functional form and include a comprehensive set of variables that have not been previously used in this context. A system of four equations using three-stage least squares is estimated. PRINCIPAL FINDINGS: We find that a higher degree of specialization leads to a decrease in costs, whereas quality certification increases costs. Costs of group practices are higher than of solo practices. The latter finding can be explained by the existence of indivisibilities of expensive technical equipment. Smaller practices do not reach the critical mass to invest in certain technologies, which leads to differences in the type of health care services provided by different practice types. CONCLUSIONS: This is the first study to use physician practices as the unit of observation and to consider the endogenous character of physician input. Our results suggest that identifying factors that influence physician practice costs is important for providing evidence-based physician payment systems and to enable decision-makers to set incentives effectively. PMID- 27193017 TI - Chia Seed Shows Good Protein Quality, Hypoglycemic Effect and Improves the Lipid Profile and Liver and Intestinal Morphology of Wistar Rats. AB - Chia has been consumed by the world population due to its high fiber, lipids and proteins content. The objective was to evaluate the protein quality of chia untreated (seed and flour) and heat treated (90 degrees C/20 min), their influence on glucose and lipid homeostasis and integrity of liver and intestinal morphology of Wistar rats. 36 male rats, weanling, divided into six groups which received control diet (casein), free protein diet (aproteic) and four diet tests (chia seed; chia seed with heat treatment; chia flour and chia flour with heat treatment) for 14 days were used. The protein efficiency ratio (PER), net protein ratio (NPR) and true digestibility (TD) were evaluated. The biochemical variables and liver and intestinal morphologies of animals were determined. The values of PER, NPR and TD did not differ among the animals that were fed with chia and were lower than the control group. The animals that were fed with chia showed lower concentrations of glucose; triacylglycerides, low-density lipoprotein cholesterol and very low-density lipoprotein and higher high-density lipoprotein cholesterol than the control group. The liver weight of animals that were fed with chia was lower than the control group. Crypt depth and thickness of intestinal muscle layers were higher in groups that were fed with chia. The consumption of chia has shown good digestibility, hypoglycemic effect, improved lipid and glycemic profiles and reduced fat deposition in liver of animals, and also promoted changes in intestinal tissue that enhanced its functionality. PMID- 27193018 TI - New Procedure to Obtain Polyphenol-Enriched Grapes Based on the Use of Chemical Elicitors. AB - The effect of the postharvest treatment of methyl jasmonate enantiomers in conjunction with ethanol on bioformation of resveratrol and quercetin glycosides in grapes was evaluated. The antioxidant activity of treated grape extracts as compared with untreated extracts was also assayed. Exogenous (-)-methyl jasmonate in combination with ethanol induced a significant increase in the levels of resveratrol (from 27 to 39 MUg g(-1)), quercetin-3-O-glucoside (from 59 to 136 MUg g(-1)), quercetin-3-O-galactoside (from 398 to 807 MUg g(-1)) and quercetin-3 O-rutinoside (from 23 to 43 MUg g(-1)). (+)-Methyl jasmonate with ethanol also resulted in increase of quercetin-3-O-glucoside and quercetin-3-O-rutinoside. However, no (+)-methyl jasmonate effect was observed for resveratrol and quercetin-3-O-galactoside. Both (-)- and (+)-methyl jasmonate treatments provided with extracts with higher antioxidant activity. From the results found in the present work postharvest treatment with (-)-methyl jasmonate in conjunction with ethanol is proposed as a mean to obtain polyphenol-enriched grape extracts with improved antioxidant properties. The procedure here developed is proposed as a mean to obtain functional grapes. Extracts obtained from grapes treated with (-) methyl jasmonate with ethanol can be particularly useful for industry due to their high antioxidant capacity. PMID- 27193021 TI - For love and money: the need to rethink benefits in HIV cure studies. AB - HIV cure research holds great potential to eradicate HIV, but the benefit to early trial participants is likely to be small. Moreover, participation carries unknown and possibly significant risks to research participants. This is the risk:benefit ratio challenge of HIV cure research. Although it may be consensual and rational for individuals to participate in HIV cure research that requires a degree of self-sacrifice, I argue that altruistic research participants can be exploited when the benefits to them are unfair. Transactions of this kind should not be prohibited, as that would be unacceptably paternalistic and thwart socially valuable research. Nevertheless, we should not simply accept these transactions but must work to reduce or eliminate exploitation by enhancing the benefits so that research participants are better off by their own lights. Offering payment in HIV cure research is the optimal way to enhance benefits to research participants and to make the risk:benefit ratio more favourable. I argue for a payment-as-benefit model against the standard view, assumed in ethics and policy, that offers of payment are not legitimate benefits. PMID- 27193022 TI - Prevalence and molecular characterization of human noroviruses and sapoviruses in Ethiopia. AB - Viral gastroenteritis is a major public health problem worldwide. In Ethiopia, very limited studies have been done on the epidemiology of enteropathogenic viruses. The aim of this study was to detect and characterize noroviruses (NoVs) and sapoviruses (SaVs) from acute gastroenteritis patients of all ages. Fecal samples were collected from diarrheic patients (n = 213) in five different health centers in Addis Ababa during June-September 2013. The samples were screened for caliciviruses by reverse transcription polymerase chain reaction (RT-PCR) using universal and genogroup-specific primer pairs. Phylogenetic analyses were conducted using the sequences of the PCR products. Of the clinical samples, 25.3 % and 4.2 % were positive for NoV and SaV RNA, respectively. Among the norovirus positives, 22 were sequenced further, and diverse norovirus strains were identified: GI (n = 4), GII (n = 17) and GIV (n = 1). Most strains were GII (n = 17/22: 77.2 %), which were further divided into three different genotypes (GII.4, GII.12/GII.g recombinant-like and GII.17), with GII.17 being the dominant (7/17) strain detected. GI noroviruses, in particular GI.4 (n = 1), GI.5 (n = 2) and GI.8 (n = 1), were also detected and characterized. The GIV strain detected is the first from East Africa. The sapoviruses sequenced were also the first reported from Ethiopia. Collectively, this study showed the high burden and diversity of noroviruses and circulation of sapoviruses in diarrheic patients in Ethiopia. Continued surveillance to assess their association with diarrhea is needed to define their epidemiology, disease burden, and impact on public health. PMID- 27193020 TI - Highly individual patterns of virus-immune IgG effector responses in humans. AB - IgG responses are fundamental to adaptive immunity and document immunological memory of previous pathogen encounter. While specific antigen recognition is mediated by the variable F(ab')2 domain of IgG, various effector functions become activated via the constant Fcgamma part bridging IgG-opsonized targets to FcgammaR-expressing immune effector cells. Traditionally, neutralizing IgG is considered the most appropriate correlate of protective humoral immunity to viruses. However, evidence is increasing that antiviral IgG mediates protection to viruses via activation of FcgammaRs. Using a test system allowing quantitative detection of virus-immune IgG able to activate FcgammaRs, sera of healthy individuals and vaccinees were assessed with regard to two prototypical human pathogenic viruses: measles and human cytomegalovirus. Marked differences in the capacity of individuals to generate FcgammaRI-, FcgammaRII- and FcgammaRIII activating responses were noted. Comparison of FcgammaR-activating IgG with neutralizing and ELISA IgG concentrations did not correlate for HCMV and only very poorly for MV. Since neither neutralizing IgG nor overall IgG responses faithfully predict the activation of FcgammaRs, only the simultaneous quantification of IgGs activating defined FcgammaRs will aid to delineate individual "immunograms" of virus IgG immunity. Such new multiparametric assessment of antiviral IgG qualities could be instrumental in defining correlates of protection and disease progression. PMID- 27193019 TI - A Retrospective Study in Adults with Metabolic Syndrome: Diabetic Risk Factor Response to Daily Consumption of Agaricus bisporus (White Button Mushrooms). AB - Adults with metabolic syndrome from different race/ethnicities are often predisposed to developing type 2 diabetes (T2D); however, growing evidence suggests that healthy diets and lifestyle choices can significantly slow or prevent progression to T2D. This poorly understood relationship to healthy dietary patterns and prevention of T2D motivated us to conduct a retrospective analysis to determine the potential impact of a minor dietary lifestyle change (daily mushroom consumption) on known T2D risk factors in racially diverse adults with confirmed features of the metabolic syndrome. Retrospectively, we studied 37 subjects who had participated in a dietary intervention focused on vitamin D bioavailability from white button mushrooms (WBM). All 37 had previously completed a 16-week study where they consumed 100 g of WBM daily and were then followed-up for one month during which no mushrooms were consumed. We analyzed differences in serum risk factors from baseline to 16-week, and from baseline to one-month follow-up. Measurement of serum diabetic risk factors included inflammatory and oxidative stress markers and the antioxidant component naturally rich in mushrooms, ergothioneine. Significant beneficial health effects were observed at 16-week with the doubling of ergothioneine from baseline, increases in the antioxidant marker ORAC (oxygen radical absorption capacity) and anti inflammatory hormone, adiponectin and significant decreases in serum oxidative stress inducing factors, carboxymethyllysine (CML) and methylglyoxal (MG), but no change in the lipid oxidative stress marker 8-isoprostane, leptin or measures of insulin resistance or glucose metabolism. We conclude that WBM contain a variety of compounds with potential anti-inflammatory and antioxidant health benefits that can occur with frequent consumption over time in adults predisposed to T2D. Well-controlled studies are needed to confirm these findings and identify the specific mushroom components beneficial to health. PMID- 27193023 TI - Elevated hepatic lipid and interferon stimulated gene expression in HCV GT3 patients relative to non-alcoholic steatohepatitis. AB - BACKGROUND AND AIMS: HCV GT-3 has a more pronounced effect on hepatic steatosis and host lipids than other HCV genotypes and is proving less responsive to all oral interferon-free treatment with direct acting antiviral agents. As both HCV GT3 infection and NASH can result in steatosis and cirrhosis, we asked whether hepatic transcriptional profiles reflective of the host response to inflammation differed based on the etiology of injury. METHODS: Hepatic gene expression was determined for 48 pre-selected genes known to be associated with hepatic interferon signaling and lipid metabolic pathways in treatment-naive HCV GT-3 (n = 9) and NASH (n = 14) patients. RESULTS: Genes with significantly higher expression in HCV included chemokines CXCL10, CXCL11 interferon IFNA2, interferon receptors IFNAR1, IL10RB negative regulators of interferon signaling SOCS3, USP18, JAK/STAT and IRF family members STAT1, STAT2, and IRF, and TGFB family members TGFB1, TGFBR1, and TGFBR2 and other ISGs like OAS2, IF127, IF144 and ISG15. HCV infection was also associated with higher expression of genes associated with lipid metabolism APOE, APOL3, SREBF1 and HMBS. Furthermore, our results suggest that, in HCV GT3-infected patients, IL28B (CC) genotype is associated with lower baseline ISG expression such as IRF9, ISG15, MX1, STAT1, CXCL10, CXCL11, and IFI27 compared to CT/TT genotype. CONCLUSIONS: HCV GT-3 and NASH both induce hepatic steatosis and inflammation, while HCV GT-3 infection is uniquely associated with elevated transcription of hepatic ISGs and genes associated with lipid metabolism. These changes likely reflect the unique host response to HCV replication distinct from the inflammatory response induced by NASH. PMID- 27193024 TI - Molecular mechanisms of HBeAg in persistent HBV infection. AB - PURPOSE: The aim of this study is to investigate the T-lymphocyte subpopulation and expression of programmed cell death-1 (PD-1), toll-like receptor (TLR)3, TLR4, and interferon (INF)-gamma to illustrate the relationship between hepatitis B e antigen (HBeAg) and persistent hepatitis B virus (HBV) infection. METHODS: Blood was taken from normal subjects into anticoagulation tubes to separate peripheral blood mononuclear cells (PBMCs). The PBMCs were divided into four groups and cultured with various concentrations of HBeAg for 72 h. Changes in the T-cell subset were analyzed through cell counting by flow cytometry, and expression of TLR3, TLR4, and PD-1 was assessed by flow cytometry and Western blot. The concentration of IFN-gamma was analyzed using enzyme-linked immunospot (ELISPOT) experiments. RESULTS: PBMCs were stimulated with various concentrations of HBeAg for 72 h and assayed by flow cytometry to determine CD4+ and CD8+ cell counts. The relative frequencies of CD4+ and CD8+ subpopulations and the CD4+/CD8+ ratio decreased compared with the control group, and T-cell impairment was significantly associated with higher HBeAg load. TLR3, TLR4, and PD-1 protein expression was assessed using flow cytometry and Western blotting. Expression of TLR3, TLR4, and PD-1 increased with increasing concentration of HBeAg. ELISPOT experiments were used to determine the concentration of IFN-gamma. IFN-gamma production in treatment groups was lower than in the control group. Comparing IFN gamma production in treatment groups, IFN-gamma production in PBMCs stimulated with high dose of HBeAg was lower than for those stimulated with low-dose HBeAg. CONCLUSIONS: HBeAg can inhibit proliferation of lymphocytes, increase TLR3, TLR4, and PD-1 expression, and decrease IFN-gamma production. This may be one of the molecular mechanisms of HBV immune tolerance. PMID- 27193027 TI - Mental Disorders Top The List Of The Most Costly Conditions In The United States: $201 Billion. AB - Estimates of annual health spending for a comprehensive set of medical conditions are presented for the entire US population and with totals benchmarked to the National Health Expenditure Accounts. In 2013 mental disorders topped the list of most costly conditions, with spending at $201 billion. PMID- 27193025 TI - Vigilance and wake EEG architecture in simulated hyperammonaemia: a pilot study on the effects of L-Ornithine-L-Aspartate (LOLA) and caffeine. AB - Hyperammonaemia/mild hepatic encephalopathy (HE) can be simulated by the oral administration of a so-called amino acid challenge (AAC). This study sought to assess the effects of the AAC alone and in combination with either ammonia lowering [L-ornithine-L-aspartate (LOLA)] or vigilance-enhancing medication (caffeine). Six patients with cirrhosis (5 males; 61.3 +/- 9.2 years; 5 Child A, 1 Child B) and six healthy volunteers (5 males; 49.8 +/- 10.6 years) were studied between 08:00 and 19:00 on Monday of three consecutive weeks. The following indices were obtained: hourly capillary ammonia, hourly subjective sleepiness, paper & pencil/computerized psychometry and wake electroencephalography (EEG) at 12:00, i.e. at the time of the maximum expected effect of the AAC. RESULTS: On average, patients had worse neuropsychological performance and slower EEG than healthy volunteers in all conditions but differences did not reach significance. In healthy volunteers, the post-AAC increase in capillary ammonia levels was contained by both the administration of LOLA and of caffeine (significant differences between 10:00 and 14:00 h). The administration of caffeine also resulted in a reduction in subjective sleepiness and in the amplitude of the EEG on several frontal/temporal-occipital sites (p < 0.05; paired t-test). Changes in ammonia levels, subjective sleepiness and the EEG in the three conditions were less obvious in patients. In conclusion, both LOLA and caffeine contained the AAC induced increase in capillary ammonia, especially in healthy volunteers. Caffeine also counteracted the AAC effects on sleepiness/EEG amplitude. The association of ammonia-lowering and vigilance-enhancing medication in the management of HE is worthy of further study. PMID- 27193028 TI - Charging overseas visitors to use NHS will benefit no one, doctors' leaders warn. PMID- 27193026 TI - The cariogenicity of commercial infant formulas: a systematic review. AB - AIM: To systematically evaluate the cariogenic potential of various commercially available infant formulas. MATERIALS AND METHODS: A literature search was conducted using Pubmed and Scopus databases for articles published between 1966 and November 2014. Reference lists of all eligible studies were searched. Only human studies were included. Data extraction and risk of bias assessments were performed. RESULTS: Seven of the 83 articles identified were included in this review, of which six studies employed plaque harvesting methods, while one study utilised an intra-oral cariogenicity/in situ model. Three studies compared milk based formulas (MBFs) and soy-based formulas (SBFs), two compared protein hydrolysate formulas (PHFs) with MBFs and SBFs, four compared formulas with various types of sugar, and two studies compared formulas with varying casein content. Based on a single study, SBFs were significantly more cariogenic than MBFs. Formulas containing only non-milk extrinsic sugars (NMES) and those containing lactose + NMES were found to be significantly more cariogenic than formulas containing only lactose. No significant correlation was found between cariogenicity and casein content in infant formula. The results of studies comparing PHFs with MBFs and SBFs were contradictory. Risk of bias assessment revealed that five studies were at moderate risk of bias, and two were assessed to be at high risk of bias. CONCLUSION: The result for cariogenicity of various types of infant formulas remains inconclusive, thus no concrete recommendations can be made. Further well-designed studies are needed to clarify the effect of casein content on cariogenicity. PMID- 27193029 TI - Diagnostic Accuracy of a New d-Dimer Assay (Sclavo Auto d-Dimer) for Exclusion of Deep Vein Thrombosis in Symptomatic Outpatients. AB - In patients presenting non-high clinical pretest probability (PTP), a negative d dimer can exclude venous thromboembolism without imaging tests. However, each d dimer assay should be validated in prospective studies. We evaluated an automated d-dimer immunoassay using the Sclavo Auto d-dimer (Sclavo Diagnostics Int, Sovicille, Italy) provided by Dasit Diagnostica (Cornaredo, Milan, Italy). Three hundred two consecutive outpatients suspected of leg deep vein thrombosis (DVT) with non-high PTP were included. The Sclavo Auto d-dimer assay was evaluated on 2 analyzers (Sysmex CA-7000 and Sysmex CS-2100; Sysmex Corporation, Kobe, Japan, provided by Dasit). The cutoff value (200 ng/mL) was established a priori. Prevalence of DVT was 11.9%. Since no false-negative patients were detected, the sensitivity and negative predictive values (NPVs) were 100% (sensitivity = CA 7000: 100% [95% confidence interval, CI: 93.3-100], CS-2100: 100% [95% CI: 93.3 100]; NPV = CA-7000: 100% [95% CI: 97.9-100], CS-2100: 100% [95% CI: 98.0-100]). Specificity was 65.4% (95% CI: 59.4-71.1) and 69.2% (95% CI: 63.3-74.7) for CA 7000 and CS-2100, respectively. Specificity increased when a higher cutoff value (234 ng/mL) was used for patients aged >=60 years without compromising the safety. Assay reproducibility was satisfactory at concentrations near the cutoff value (total coefficient of variations <10%). In conclusion, the Sclavo Auto d dimer assay was accurate when used for DVT diagnostic workup in outpatients with non-high PTP. Based on its high sensitivity and NPV, it can be used as a stand alone test in outpatients with non-high PTP. Given its high specificity, the number of patients in whom further imaging techniques can be avoided increased, improving the yield of the test. PMID- 27193030 TI - Lipid-based Vesicular Nanocargoes as Nanotherapeutic Targets for the Effective Management of Rheumatoid Arthritis. AB - BACKGROUND: Rheumatoid arthritis (RA) is an immune mediated joint-based chronic inflammatory disorder recognized by joint inflammation, destruction, pain and remission. Currently, numerous pharmacotherapeutic strategies have gained immense popularity in RA therapy and improving the patient life. METHODS: Besides, it exhibits numerous drawbacks such as requirement of high dose of drugs, unavoidable adverse effects and diseases remission. Thus, use of currently available pharmacotherapeutics employing conventional formulations can only provide therapeutic effects to a certain extent. RESULTS: Recent advancements in nanotechnology-based lipidic vesicular nanocarriers have led provided improved efficacy and safety for the anti-rheumatic drugs. These include liposomes, stealth liposomes, ethosomes, transfersomes, etc., which have shown their potential to improve the therapeutic efficacy of antirheumatic drugs with lesser toxicity. Although the results of animal models for use of lipid vesicular nanocarriers for drug targeting in RA have been found to be highly promising, but lack of sufficient data in a clinical setup are still evident to demonstrate their practical utility in patient populations. In this regard, considerable research studies are required for evaluating the efficacy and safety of the aforementioned nanocarriers in RA through clinical studies. CONCLUSION: The present review, therefore, covers the brief pathophysiology of RA, current medication and their challenges in RA therapy. Besides, an extensive account on recent advancements in novel lipid vesicular nanocarriers in RA therapy has also been addressed with special emphasis on the patent literature too. PMID- 27193031 TI - A combined large-scale meta-analysis identifies COG6 as a novel shared risk locus for rheumatoid arthritis and systemic lupus erythematosus. AB - OBJECTIVES: During the last years, genome-wide association studies (GWASs) have identified a number of common genetic risk factors for rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, the genetic overlap between these two immune-mediated diseases has not been thoroughly examined so far. The aim of the present study was to identify additional risk loci shared between RA and SLE. METHODS: We performed a large-scale meta-analysis of GWAS data from RA (3911 cases and 4083 controls) and SLE (2237 cases and 6315 controls). The top associated polymorphisms in the discovery phase were selected for replication in additional datasets comprising 13 641 RA cases and 31 921 controls and 1957 patients with SLE and 4588 controls. RESULTS: The rs9603612 genetic variant, located nearby the COG6 gene, an established susceptibility locus for RA, reached genome-wide significance in the combined analysis including both discovery and replication sets (p value=2.95E-13). In silico expression quantitative trait locus analysis revealed that the associated polymorphism acts as a regulatory variant influencing COG6 expression. Moreover, protein-protein interaction and gene ontology enrichment analyses suggested the existence of overlap with specific biological processes, specially the type I interferon signalling pathway. Finally, genetic correlation and polygenic risk score analyses showed cross-phenotype associations between RA and SLE. CONCLUSIONS: In conclusion, we have identified a new risk locus shared between RA and SLE through a meta analysis including GWAS datasets of both diseases. This study represents the first comprehensive large-scale analysis on the genetic overlap between these two complex disorders. PMID- 27193032 TI - When doctors share visit notes with patients: a study of patient and doctor perceptions of documentation errors, safety opportunities and the patient-doctor relationship. AB - BACKGROUND: Patient advocates and safety experts encourage adoption of transparent health records, but sceptics worry that shared notes may offend patients, erode trust or promote defensive medicine. As electronic health records disseminate, such disparate views fuel policy debates about risks and benefits of sharing visit notes with patients through portals. METHODS: Presurveys and postsurveys from 99 volunteer doctors at three US sites who participated in OpenNotes and postsurveys from 4592 patients who read at least one note and submitted a survey. RESULTS: Patients read notes to be better informed and because they were curious; about a third read them to check accuracy. In total, 7% (331) of patients reported contacting their doctor's office about their note. Of these, 29% perceived an error, and 85% were satisfied with its resolution. Nearly all patients reported feeling better (37%) or the same (62%) about their doctor. Patients who were older (>63), male, non-white, had fair/poor self reported health or had less formal education were more likely to report feeling better about their doctor. Among doctors, 26% anticipated documentation errors, and 44% thought patients would disagree with notes. After a year, 53% believed patient satisfaction increased, and 51% thought patients trusted them more. None reported ordering more tests or referrals. CONCLUSIONS: Despite concerns about errors, offending language or defensive practice, transparent notes overall did not harm the patient-doctor relationship. Rather, doctors and patients perceived relational benefits. Traditionally more vulnerable populations-non-white, those with poorer self-reported health and those with fewer years of formal education may be particularly likely to feel better about their doctor after reading their notes. Further informing debate about OpenNotes, the findings suggest transparent records may improve patient satisfaction, trust and safety. PMID- 27193033 TI - Cognitive tests predict real-world errors: the relationship between drug name confusion rates in laboratory-based memory and perception tests and corresponding error rates in large pharmacy chains. AB - BACKGROUND: Drug name confusion is a common type of medication error and a persistent threat to patient safety. In the USA, roughly one per thousand prescriptions results in the wrong drug being filled, and most of these errors involve drug names that look or sound alike. Prior to approval, drug names undergo a variety of tests to assess their potential for confusability, but none of these preapproval tests has been shown to predict real-world error rates. OBJECTIVES: We conducted a study to assess the association between error rates in laboratory-based tests of drug name memory and perception and real-world drug name confusion error rates. METHODS: Eighty participants, comprising doctors, nurses, pharmacists, technicians and lay people, completed a battery of laboratory tests assessing visual perception, auditory perception and short-term memory of look-alike and sound-alike drug name pairs (eg, hydroxyzine/hydralazine). RESULTS: Laboratory test error rates (and other metrics) significantly predicted real-world error rates obtained from a large, outpatient pharmacy chain, with the best-fitting model accounting for 37% of the variance in real-world error rates. Cross-validation analyses confirmed these results, showing that the laboratory tests also predicted errors from a second pharmacy chain, with 45% of the variance being explained by the laboratory test data. CONCLUSIONS: Across two distinct pharmacy chains, there is a strong and significant association between drug name confusion error rates observed in the real world and those observed in laboratory-based tests of memory and perception. Regulators and drug companies seeking a validated preapproval method for identifying confusing drug names ought to consider using these simple tests. By using a standard battery of memory and perception tests, it should be possible to reduce the number of confusing look-alike and sound-alike drug name pairs that reach the market, which will help protect patients from potentially harmful medication errors. PMID- 27193034 TI - PPAR-alpha, a lipid-sensing transcription factor, regulates blood-brain barrier efflux transporter expression. AB - Lipid sensor peroxisome proliferator-activated receptor alpha (PPAR- alpha) is the master regulator of lipid metabolism. Dietary release of endogenous free fatty acids, fibrates, and certain persistent environmental pollutants, e.g. perfluoroalkyl fire-fighting foam components, are peroxisome proliferator activated receptor alpha ligands. Here, we define a role for peroxisome proliferator-activated receptor alpha in regulating the expression of three ATP driven drug efflux transporters at the rat and mouse blood-brain barriers: P glycoprotein (Abcb1), breast cancer resistance protein (Bcrp/Abcg2), and multidrug resistance-associated protein 2 (Mrp2/Abcc2). Exposing isolated rat brain capillaries to linoleic acid, clofibrate, or PKAs increased the transport activity and protein expression of the three ABC transporters. These effects were blocked by the PPAR- alpha antagonist, GW6471. Dosing rats with 20 mg/kg or 200 mg/kg of clofibrate decreased the brain accumulation of the P-glycoprotein substrate, verapamil, by 50% (in situ brain perfusion; effects blocked by GW6471) and increased P-glycoprotein expression and activity in capillaries ex vivo. Fasting C57Bl/6 wild-type mice for 24 h increased both serum lipids and brain capillary P-glycoprotein transport activity. Fasting did not alter P-glycoprotein activity in PPAR- alpha knockout mice. These results indicate that hyperlipidemia, lipid-lowering fibrates and exposure to certain fire-fighting foam components activate blood-brain barrier peroxisome proliferator-activated receptor alpha, increase drug efflux transporter expression and reduce drug delivery to the brain. PMID- 27193037 TI - Pathological Effects of the FMR1 CGG-Repeat Polymorphism (5-55 Repeat Numbers): Systematic Review and Meta-Analysis. AB - The fragile X mental retardation 1 (FMR1) gene contains a highly polymorphic trinucleotide (CGG) repeat and consists of various allelic forms. Traditionally, 55-200 repeats and over 200 CGG repeats have been highlighted to be associated with ovarian dysfunction and neuro-psychiatric risks. However, previous studies had paid little attention to the allelic forms of 5-55 CGG repeats. Herein, we sought to evaluate the pathological features of FMR1 allelic category with a range of 5-55 CGG repeats. We further classified the spectrum of CGG sizes (5-55 repeats) into three sub-groups as low numbers of CGG repeat (< 26 repeats), normal CGG count (26-34 repeats), and small CGG expansion (35-54 repeats). Our systematic review documented that low numbers of CGG repeat (< 26 repeats) revealed a close relationship with premature ovarian failure. Correspondingly, the meta-analysis showed that small CGG expansion, involving allelic sizes with 35-54 (n = 8, OR = 1.22, 95% CI: 0.75-2.00, P > 0.05) and 41-54 (n = 7, OR = 1.62, 95% CI: 1.14-2.30, P < 0.05), was both linked to the risk of ovarian dysfunction. Additionally, small CGG expansion exerts significant influence on male Parkinsonism cohorts (OR = 2.17, 95% CI: 1.50-3.14, P < 0.05), mental retardation, and repeat instability. Our data provide evidence that the CGG repeat numbers below 26 or above 34 of FMR1 gene are also associated with disease risks and thus should be regarded as pathological genotypes for a routine test. PMID- 27193035 TI - Aging-related alterations in eNOS and nNOS responsiveness and smooth muscle reactivity of murine basilar arteries are modulated by apocynin and phosphorylation of myosin phosphatase targeting subunit-1. AB - Aging causes major alterations of all components of the neurovascular unit and compromises brain blood supply. Here, we tested how aging affects vascular reactivity in basilar arteries from young (<10 weeks; y-BA), old (>22 months; o BA) and old (>22 months) heterozygous MYPT1-T-696A/+ knock-in mice. In isometrically mounted o-BA, media thickness was increased by ~10% while the passive length tension relations were not altered. Endothelial denudation or pan NOS inhibition (100 umol/L L-NAME) increased the basal tone by 11% in y-BA and 23% in o-BA, while inhibition of nNOS (1 umol/L L-NPA) induced ~10% increase in both ages. eNOS expression was ~2-fold higher in o-BA. In o-BA, U46619-induced force was augmented (pEC50 ~6.9 vs. pEC50 ~6.5) while responsiveness to DEA NONOate, electrical field stimulation or nicotine was decreased. Basal phosphorylation of MLC20-S19 and MYPT1-T-853 was higher in o-BA and was reversed by apocynin. Furthermore, permeabilized o-BA showed enhanced Ca2+-sensitivity. Old T-696A/+ BA displayed a reduced phosphorylation of MYPT1-T696 and MLC20, a lower basal tone in response to L-NAME and a reduced eNOS expression. The results indicate that the vascular hypercontractility found in o-BA is mediated by inhibition of MLCP and is partially compensated by an upregulation of endothelial NO release. PMID- 27193038 TI - The Severity of Takayasu Arteritis Is Associated with the HLA-B52 Allele in Japanese Patients. AB - Takayasu arteritis (TA) is a type of vasculitis that affects the large elastic arteries, specifically the aorta and its main branches. It has been reported that TA occurred most frequently in Nagasaki Prefecture, the western area in Japan. We retrospectively collected the information of 34 patients with TA, diagnosed using the American College of Rheumatology 1990 criteria for the classification of TA, from the medical records of Nagasaki University Hospital from 2003 to 2015, and we investigated the clinical characteristics of these TA patients. Among the 35 patients, 25 patients were examined for the existence of the HLA-B52 allele that has been reported to influence TA susceptibility. Seventeen patients (68.0%) of the 25 patients were HLA-B52-allele-positive, which was defined as the state of having at least one HLA-B52 allele. There was a significant difference in the rate of smokers: HLA-B52-allele-positive: six patients (35.3%) vs. HLA-B52-allele negative: 0 (0.0%). The C-reactive protein level in the HLA-B52-positive patients (9.0 +/- 6.4 mg/dL) was significantly higher than that in the HLA-B52-negative patients (3.2 +/- 3.9 mg/dL). All HLA-B52-allele-positive patients were found to be active according to Kerr's criteria. The HLA-B52-positive patients' initial prednisolone dosage (37.7 +/- 8.6 mg/day) was significantly higher than that of the HLA-B52-allele-negative patients (23.1 +/- 13.1 mg/day). Thus, the HLA-B52 allele is associated with the disease activity and the steroid requirements of TA patients. Furthermore, our present findings have revealed for the first time that the HLA-B52 allele and smoking might be associated with the onset of TA. PMID- 27193036 TI - Mobile Technology for Vegetable Consumption: A Randomized Controlled Pilot Study in Overweight Adults. AB - BACKGROUND: Mobile apps present a potentially cost-effective tool for delivering behavior change interventions at scale, but no known studies have tested the efficacy of apps as a tool to specifically increase vegetable consumption among overweight adults. OBJECTIVE: The purpose of this pilot study was to assess the initial efficacy and user acceptability of a theory-driven mobile app to increase vegetable consumption. METHODS: A total of 17 overweight adults aged 42.0 (SD 7.3) years with a body mass index (BMI) of 32.0 (SD 3.5) kg/m(2) were randomized to the use of Vegethon (a fully automated theory-driven mobile app enabling self monitoring of vegetable consumption, goal setting, feedback, and social comparison) or a wait-listed control condition. All participants were recruited from an ongoing 12-month weight loss trial (parent trial). Researchers who performed data analysis were blinded to condition assignment. The primary outcome measure was daily vegetable consumption, assessed using an adapted version of the validated Harvard Food Frequency Questionnaire administered at baseline and 12 weeks after randomization. An analysis of covariance was used to assess differences in 12-week vegetable consumption between intervention and control conditions, controlling for baseline. App usability and satisfaction were measured via a 21-item post-intervention questionnaire. RESULTS: Using intention to-treat analyses, all enrolled participants (intervention: 8; control: 9) were analyzed. Of the 8 participants randomized to the intervention, 5 downloaded the app and logged their vegetable consumption a mean of 0.7 (SD 0.9) times per day, 2 downloaded the app but did not use it, and 1 never downloaded it. Consumption of vegetables was significantly greater among the intervention versus control condition at the end of the 12-week pilot study (adjusted mean difference: 7.4 servings; 95% CI 1.4-13.5; P=.02). Among secondary outcomes defined a priori, there was significantly greater consumption of green leafy vegetables, cruciferous vegetables, and dark yellow vegetables (adjusted mean difference: 2.6, 1.6, and 0.8 servings; 95% CI 0.1-5.0, 0.1-3.2, and 0.3-1.4; P=.04, P=.04, and P=.004, respectively). Participants reported positive experiences with the app, including strong agreement with the statements "I have found Vegethon easy to use" and "I would recommend Vegethon to a friend" (mean 4.6 (SD 0.6) and 4.2 (SD 0.8), respectively, (on a 5-point scale). CONCLUSIONS: Vegethon demonstrated initial efficacy and user acceptability. A mobile app intervention may be useful for increasing vegetable consumption among overweight adults. The small sample size prevented precise estimates of effect sizes. Given the improved health outcomes associated with increases in vegetable consumption, these findings indicate the need for larger, longer-term evaluations of Vegethon and similar technologies among overweight adults and other suitable target groups. TRIAL REGISTRATION: ClinicalTrials.gov NCT01826591; https://clinicaltrials.gov/ct2/show/NCT01826591 (Archived by WebCite at http://www.webcitation.org/6hYDw2AOB). PMID- 27193039 TI - Immunoglobulin M for Acute Infection: True or False? AB - Immunoglobulin M (IgM) tests have clear clinical utility but also suffer disproportionately from false-positive results, which in turn can lead to misdiagnoses, inappropriate therapy, and premature closure of a diagnostic workup. Despite numerous reports in the literature, many clinicians and laboratorians remain unaware of this issue. In this brief review, a series of virology case examples is presented. However, a false-positive IgM can occur with any pathogen. Thus, when an accurate diagnosis is essential for therapy, prognosis, infection control, or public health, when the patient is sick enough to be hospitalized, or when the clinical or epidemiologic findings do not fit, IgM detection should not be accepted as a stand-alone test. Rather, whenever possible, the diagnosis should be confirmed by other means, including testing of serial samples and the application of additional test methods. PMID- 27193043 TI - Improving Sexual Function Recovery Following RARP: Impact of Surgeon Technique Versus the Role of Anti-Inflammatory Agents?, Editorial Comment for Patel et al. PMID- 27193042 TI - Recalcitrant steroid-induced rosacea successfully treated with 0.03% tacrolimus and 595-nm pulsed dye laser. PMID- 27193041 TI - Circulating Gut-Homing (alpha4beta7+) Plasmablast Responses against Shigella Surface Protein Antigens among Hospitalized Patients with Diarrhea. AB - Developing countries are burdened with Shigella diarrhea. Understanding mucosal immune responses associated with natural Shigella infection is important to identify potential correlates of protection and, as such, to design effective vaccines. We performed a comparative analysis of circulating mucosal plasmablasts producing specific antibodies against highly conserved invasive plasmid antigens (IpaC, IpaD20, and IpaD120) and two recently identified surface protein antigens, pan-Shigella surface protein antigen 1 (PSSP1) and PSSP2, common to all virulent Shigella strains. We examined blood and stool specimens from 37 diarrheal patients admitted to the Infectious Diseases & Beliaghata General Hospital, Kolkata, India. The etiological agent of diarrhea was investigated in stool specimens by microbiological methods and real-time PCR. Gut-homing (alpha4beta7 (+)) antibody-secreting cells (ASCs) were isolated from patient blood by means of combined magnetic cell sorting and two-color enzyme-linked immunosorbent spot (ELISPOT) assay. Overall, 57% (21 of 37) and 65% (24 of 37) of the patients were positive for Shigella infection by microbiological and real-time PCR assays, respectively. The frequency of alpha4beta7 (+) IgG ASC responders against Ipas was higher than that observed against PSSP1 or PSSP2, regardless of the Shigella serotype isolated from these patients. Thus, alpha4beta7 (+) ASC responses to Ipas may be considered an indirect marker of Shigella infection. The apparent weakness of ASC responses to PSSP1 is consistent with the lack of cross protection induced by natural Shigella infection. The finding that ASC responses to IpaD develop in patients with recent-onset shigellosis indicates that such responses may not be protective or may wane too rapidly and/or be of insufficient magnitude. PMID- 27193040 TI - An HIV gp120-CD4 Immunogen Does Not Elicit Autoimmune Antibody Responses in Cynomolgus Macaques. AB - A promising concept for human immunodeficiency virus (HIV) vaccines focuses immunity on the highly conserved transition state structures and epitopes that appear when the HIV glycoprotein gp120 binds to its receptor, CD4. We are developing chimeric antigens (full-length single chain, or FLSC) in which gp120 and CD4 sequences are flexibly linked to allow stable intrachain complex formation between the two moieties (A. DeVico et al., Proc Natl Acad Sci U S A 104:17477-17482, 2007, doi:10.1073/pnas.0707399104; T. R. Fouts et al., J Virol 74:11427-11436, 2000, doi:10.1128/JVI.74.24.11427-11436.2000). Proof of concept studies with nonhuman primates show that FLSC elicited heterologous protection against simian-human immunodeficiency virus (SHIV)/simian immunodeficiency virus (SIV) (T. R. Fouts et al., Proc Natl Acad Sci U S A 112:E992-E999, 2016, doi:10.1073/pnas.1423669112), which correlated with antibodies against transition state gp120 epitopes. Nevertheless, advancement of any vaccine that comprises gp120-CD4 complexes must consider whether the CD4 component breaks tolerance and becomes immunogenic in the autologous host. To address this, we performed an immunotoxicology study with cynomolgus macaques vaccinated with either FLSC or a rhesus variant of FLSC containing macaque CD4 sequences (rhFLSC). Enzyme-linked immunosorbent assay (ELISA) binding titers, primary CD3(+) T cell staining, and temporal trends in T cell subset frequencies served to assess whether anti-CD4 autoantibody responses were elicited by vaccination. We find that immunization with multiple high doses of rhFLSC did not elicit detectable antibody titers despite robust responses to rhFLSC. In accordance with these findings, immunized animals had no changes in circulating CD4(+) T cell counts or evidence of autoantibody reactivity with cell surface CD4 on primary naive macaque T cells. Collectively, these studies show that antigens using CD4 sequences to stabilize transition state gp120 structures are unlikely to elicit autoimmune antibody responses, supporting the advancement of gp120-CD4 complex-based antigens, such as FLSC, into clinical testing. PMID- 27193044 TI - Switching of an Azobenzene-Tripod Molecule on Ag(111). AB - The trans-cis isomerization makes azobenzene (AB) a robust molecular switch. Once adsorbed to a metal, however, the switching is inefficient or absent due to rapid excited-state quenching or loss of the trans-cis bistability. We find that tris [4-(phenylazo)-phenyl]-amine is a rather efficient switch on Ag(111). Using scanning tunneling and atomic force microscopy at submolecular resolution along with density functional theory calculations, we show that the switching process is no trans-cis isomerization but rather a reorientation of the N-N bond of an AB unit. It proceeds through a twisting motion of the azo-bridge that leads to a lateral shift of a phenyl ring. Thus, the role of the Ag substrate is ambivalent. While it suppresses the original bistability of the azobenzene units, it creates a new one by inducing a barrier for the rotation of the N-N bond. PMID- 27193045 TI - The Effect of Variation of Plyometric Push-Ups on Force-Application Kinetics and Perception of Intensity. AB - PURPOSE: To examine differences between ground-reaction-force (GRF)-based parameters collected from 5 types of plyometric push-ups. Between-trials reliability and the relationships between parameters were also assessed. METHODS: Thirty-seven highly active commando soldiers performed 3 trials of 5 variations of the plyometric push-up in a counterbalanced order: standard countermovement push-up (SCPu), standard squat push-up (SSPu), kneeling countermovement push-up (KCPu), kneeling squat push-up (KSPu), and drop-fall push-up (DFPu). Vertical GRF was measured during these exercises using a portable Kistler force plate. The GRF applied by the hands in the starting position (initial force supported), peak GRF and rate of force development during takeoff, flight time, impact force, and rate of force development impact on landing were determined. RESULTS: During standard position exercises (SCPu and SSPu) the initial force supported and impact force were higher (P < .001) than with kneeling exercises (KCPu, KSPu, and DFPu). The peak GRF and rate of force development during takeoff were higher (P < .001) in the countermovement push-up exercises ([CMP] SCPu, KCPu, and DFPu) than squat push-up exercises ([SP] SSPu and KSPu). Furthermore, the flight time was greater (P < .001) during kneeling exercises than during standard-position exercises. A significant relationship (P < .01) between impact force and the rate of force development impact was observed for CMP and SP exercises (r = .83 and r = .62, respectively). The initial force supported was also negatively related (P < .01) to the flight time for both CMP and SP (r = -.74 and r = -.80, respectively). It was revealed that the initial force supported and the peak GRF during takeoff had excellent reliability; however, other parameters had poor absolute reliability. CONCLUSIONS: It is possible to adjust the intensity of plyometric push-up exercises and train athletes' muscle power by correctly interpreting GRF-based parameters. However, caution is required as some parameters had marginal absolute reliability. PMID- 27193046 TI - Gender Differences in Spousal Care Across the Later Life Course. AB - Spouses often serve as the primary caregivers to their ill or disabled partners. Studies have shown that men receive more care from their wives than vice versa, but few studies have focused on how the gender gap in care varies across the later life course. Drawing on data from the Health and Retirement Study, this study examined the moderating effects of age, gender, and full-time employment on married women's and men's receipt of spousal care. This study found that among community-dwelling married adults, the gender gap in care was larger among those in middle age (50-65) than it was among those in older age. As women and men aged, the gender gap decreased primarily because men left full-time work and increased the amount of time that they spent caring for their wives. As gender differences in full-time employment narrowed, the gender gap in spousal care narrowed. PMID- 27193048 TI - A Longitudinal Analysis of Site of Death: The Effects of Continuous Enrollment in Medicare Advantage Versus Conventional Medicare. AB - This study assessed the odds of dying in hospital associated with enrollment in Medicare Advantage (M-A) versus conventional Medicare Fee-for-Service (M-FFS). Data were derived from the 2008 and 2010 waves of the Health and Retirement Study ( n = 1,030). The sample consisted of elderly Medicare beneficiaries who died in 2008-2010 (34% died in hospital, and 66% died at home, in long-term senior care, a hospice facility, or other setting). Logistic regression estimated the odds of dying in hospital for those continuously enrolled in M-A from 2008 until death compared to those continuously enrolled in M-FFS and those switching between the two plans. Results indicate that decedents continuously enrolled in M-A had 43% lower odds of dying in hospital compared to those continuously enrolled in M-FFS. Financial incentives in M-A contracts may reduce the odds of dying in hospital. PMID- 27193050 TI - Laser Measurements of the H Atom + Ozone Rate Constant at Mesospheric Temperatures. AB - The exothermic H + O3 reaction produces OH(v) Meinel band emissions, used to derive mesospheric H concentrations and chemical heating rates. We remeasured its rate constant to reduce its uncertainty and extended the measurements to lower mesospheric temperatures using modern laser-induced fluorescence (LIF) techniques. H atoms were produced by pulsed ultraviolet laser trace photolysis of O3, followed by reaction of O((1)D) with added H2. A second, delayed, frequency mixed dye laser measured the reaction decay rate with the remaining ozone using LIF. We monitored either the H atom decay by two photon excitation at 205 nm and detection of red fluorescence, or the OH (v = 9) product time evolution with excitation of the B(2)Sigma(+)-X(2)Pi (0,9) band at 237 nm and emission in the blue B(2)Sigma(+)-A(2)Sigma(+) (0,7) band. By cooling the enclosed low pressure flow cell we obtained measurements from 140 to 305 K at 20 to 200 Torr in Ar. Small kinetic modeling corrections were made for secondary regeneration of H atoms. The results are consistent with the current NASA JPL recommendation for this rate constant and establish its extrapolation down to the lower temperatures of the mesosphere. PMID- 27193047 TI - Disparities in Mental Health Quality of Life Between Hispanic and Non-Hispanic White LGB Midlife and Older Adults and the Influence of Lifetime Discrimination, Social Connectedness, Socioeconomic Status, and Perceived Stress. AB - We assessed factors contributing to ethnic and racial disparities in mental health quality of life (MHQOL) among lesbian, gay, and bisexual (LGB) midlife and older adults. We utilized cross-sectional survey data from a sample of non Hispanic White and Hispanic LGB adults aged 50 and older. Structural equation modeling was used to test the indirect effect of ethnicity/race on MHQOL via explanatory factors including social connectedness, lifetime discrimination, socioeconomic status (SES), and perceived stress. Hispanics reported significantly lower levels of MHQOL, compared to non-Hispanic Whites. In the final model, the association between ethnicity/race and MHQOL was explained by higher levels of perceived stress related to lower SES, higher frequency of lifetime discrimination, and lack of social connectedness among Hispanic LGB adults. This study suggests that perceived stress related to social disadvantage and marginalization plays an important role in MHQOL disparities among Hispanic LGB midlife and older adults. PMID- 27193049 TI - Histone deacetylase inhibitor SAHA attenuates post-seizure hippocampal microglia TLR4/MYD88 signaling and inhibits TLR4 gene expression via histone acetylation. AB - BACKGROUND: Epilepsy is a common neurological disorder characterized by recurrent unprovoked seizures. Seizure-induced TLR4/MYD88 signaling plays a critical role in activating microglia and triggering neuron apoptosis. SAHA is a histone deacetylase inhibitor that regulates gene expression by increasing chromatin histone acetylation. In this study, we investigated the role of SAHA in TLR4/MYD88 signaling in a rat seizure model. RESULTS: Sprague-Dawley rats with kainic acid (KA)-induced seizures were treated with SAHA. The expression of TLR4, MYD88, NF-kappaB P65 and IL-1beta in hippocampus was detected at hour 2 and 6 and day 1, 2, and 3 post seizure. SAHA pretreatment increased seizure latency and decreased seizure scores. The expression levels of TLR4, MYD88, NF-kappaB and IL 1beta increased significantly in both activated microglia and apoptotic neurons after KA treatment. The effects were attenuated by SAHA. Chromatin immunoprecipitation assays indicated that the H3 histone acetylation levels significantly decreased while H3K9 levels significantly increased in the KA treatment group. The H3 and H3K9 acetylation levels returned to control levels after SAHA (50 mg/kg) pretreatment. There was a positive correlation between the expression of TLR4 and the acetylation levels of H3K9. CONCLUSIONS: Histone deacetylase inhibitor SAHA can suppress seizure-induced TLR4/MYD88 signaling and inhibit TLR4 gene expression through histone acetylation regulation. This suggests that SAHA may protect against seizure-induced brain damage. PMID- 27193051 TI - The association between exposure and psychological health in earthquake survivors from the Longmen Shan Fault area: the mediating effect of risk perception. AB - BACKGROUND: In this study, exposure refers to survivors who suffered from life changing situations, such as personal injuries, the deaths or injury of family members, relatives or friends or the loss of or damage to personal or family property, as a result of the earthquake. The mediating effect of risk perception on the exposure and psychological health in survivors from the Longmen Shan Fault area and the moderating effect of social support on the relationship between risk perception and psychological health were both examined. METHOD: A cross-sectional survey was conducted in a local Longmen Shan Fault area near the epicenter of the 2008 Wenchuan earthquake. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), the standard Chinese 12-item Short Form (SF 12v2), and the Social Support Rating Scale (SSRS) were used to interview 2,080 earthquake survivors in the period one-year after the earthquake. Based on the environment and the characteristics of the Longmen Shan Fault area, a risk perception questionnaire was developed to evaluate survivor risk perception. Factor and regression analyses were conducted to determine the hypothetical relations. RESULTS: The analyses provided effective support for the hypothesized model. Survivor risk perception was classified into direct risk perception and indirect risk perception. Survivor direct risk perception was found to play a partial mediating role in the relationship between exposure and the two domains (Physical component summary (PCS) and the Mental component summary (MCS)) of psychological health. Survivor indirect risk perception was found to have a only partial mediating effect on the association between exposure and MCS. Social support was found to moderate the influence of risk perception on psychological health. CONCLUSION: Risk communication should be considered in future post earthquake psychological assistance programs and social support strategies could also be useful in improving psychological health. PMID- 27193052 TI - Transgene Reactivation in Induced Pluripotent Stem Cell Derivatives and Reversion to Pluripotency of Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells. AB - Induced pluripotent stem cells (iPSCs) have enormous potential in regenerative medicine and disease modeling. It is now felt that clinical trials should be performed with iPSCs derived with nonintegrative constructs. Numerous studies, however, including those describing disease models, are still being published using cells derived from iPSCs generated with integrative constructs. Our experimental work presents the first evidence of spontaneous transgene reactivation in vitro in several cellular types. Our results show that the transgenes were predominantly silent in parent iPSCs, but in mesenchymal and endothelial iPSC derivatives, the transgenes experienced random upregulation of Nanog and c-Myc. Additionally, we provide evidence of spontaneous secondary reprogramming and reversion to pluripotency in mesenchymal stem cells derived from iPSCs. These findings strongly suggest that the studies, which use cellular products derived from iPSCs generated with retro- or lentiviruses, should be evaluated with consideration of the possibility of transgene reactivation. The in vitro model described here provides insight into the earliest events of culture transformation and suggests the hypothesis that reversion to pluripotency may be responsible for the development of tumors in cell replacement experiments. The main goal of this work, however, is to communicate the possibility of transgene reactivation in retro- or lenti-iPSC derivatives and the associated loss of cellular fidelity in vitro, which may impact the outcomes of disease modeling and related experimentation. PMID- 27193053 TI - Exploring the interaction among EPHX1, GSTP1, SERPINE2, and TGFB1 contributing to the quantitative traits of chronic obstructive pulmonary disease in Chinese Han population. AB - BACKGROUND: Currently, the majority of genetic association studies on chronic obstructive pulmonary disease (COPD) risk focused on identifying the individual effects of single nucleotide polymorphisms (SNPs) as well as their interaction effects on the disease. However, conventional genetic studies often use binary disease status as the primary phenotype, but for COPD, many quantitative traits have the potential correlation with the disease status and closely reflect pathological changes. METHOD: Here, we genotyped 44 SNPs from four genes (EPHX1, GSTP1, SERPINE2, and TGFB1) in 310 patients and 203 controls which belonged to the Chinese Han population to test the two-way and three-way genetic interactions with COPD-related quantitative traits using recently developed generalized multifactor dimensionality reduction (GMDR) and quantitative multifactor dimensionality reduction (QMDR) algorithms. RESULTS: Based on the 310 patients and the whole samples of 513 subjects, the best gene-gene interactions models were detected for four lung-function-related quantitative traits. For the forced expiratory volume in 1 s (FEV1), the best interaction was seen from EPHX1, SERPINE2, and GSTP1. For FEV1%pre, the forced vital capacity (FVC), and FEV1/FVC, the best interactions were seen from SERPINE2 and TGFB1. CONCLUSION: The results of this study provide further evidence for the genotype combinations at risk of developing COPD in Chinese Han population and improve the understanding on the genetic etiology of COPD and COPD-related quantitative traits. PMID- 27193055 TI - Analysis of 4931 renal biopsy data in central China from 1994 to 2014. AB - The purpose of this study is to investigate the changing spectrum and clinicopathologic correlation of biopsy-proven renal diseases in central China. We retrospectively analyzed data of 4931 patients who underwent renal biopsy in ten hospitals between September 1994 and December 2014. Among them, 81.55% were primary glomerular diseases (GD), and 13.02% were secondary GD. IgA nephropathy (IgAN) was the most common primary GD (43.45%), followed by focal glomerulonephritis (16.79%), mesangial proliferative glomerulonephritis (MsPGN, 14.35%), and membranous nephropathy (MN, 13.28%). IgAN was leading primary GD in patients under 60 years old, while MN was the leading one over 60 years old. The most frequent secondary GD was lupus nephritis (LN) (47.35%). The prevalence of IgAN, MN and minimal change disease was found to increase significantly (p < 0.001, p < 0.001, and p < 0.01, respectively), while that of MsPGN, membranoproliferative glomerulonephritis and LN decreased significantly (p < 0.001, p < 0.001, and p < 0.05, respectively). The main indication for renal biopsy was proteinuria and hematuria (49.03%), followed by nephrotic syndrome (NS, 20.36%). IgAN was the most common cause in patients with proteinuria and hematuria, chronic-progressive kidney injury, hematuria and acute kidney injury; and MN was the leading cause of NS. Primary GD remained the predominant renal disease in central China. IgAN and LN were the most prevalent histopathologic lesions of primary and secondary GD, respectively. The spectrum of biopsy-proven renal disease had a great change in the past two decades. Proteinuria and hematuria was the main indication for renal biopsy. PMID- 27193057 TI - Quantum coherence and quantum phase transitions. AB - We study the connections between local quantum coherence (LQC) based on Wigner Yanase skew information and quantum phase transitions (QPTs). When applied on the one-dimensional Hubbard, XY spin chain with three-spin interaction, and Su Schrieffer-Heeger models, the LQC and its derivatives are used successfully to detect different types of QPTs in these spin and fermionic systems. Furthermore, the LQC is effective as the quantum discord (QD) in detecting QPTs at finite temperatures, where the entanglement has lost its effectiveness. We also demonstrate that the LQC can exhibit different behaviors in many forms compared with the QD. PMID- 27193056 TI - In actio optophysiological analyses reveal functional diversification of dopaminergic neurons in the nematode C. elegans. AB - Many neuronal groups such as dopamine-releasing (dopaminergic) neurons are functionally divergent, although the details of such divergence are not well understood. Dopamine in the nematode Caenorhabditis elegans modulates various neural functions and is released from four left-right pairs of neurons. The terminal identities of these dopaminergic neurons are regulated by the same genetic program, and previous studies have suggested that they are functionally redundant. In this study, however, we show functional divergence within the dopaminergic neurons of C. elegans. Because dopaminergic neurons of the animals were supposedly activated by mechanical stimulus upon entry into a lawn of their food bacteria, we developed a novel integrated microscope system that can auto track a freely-moving (in actio) C. elegans to individually monitor and stimulate the neuronal activities of multiple neurons. We found that only head-dorsal pair of dopaminergic neurons (CEPD), but not head-ventral or posterior pairs, were preferentially activated upon food entry. In addition, the optogenetic activation of CEPD neurons alone exhibited effects similar to those observed upon food entry. Thus, our results demonstrated functional divergence in the genetically similar dopaminergic neurons, which may provide a new entry point toward understanding functional diversity of neurons beyond genetic terminal identification. PMID- 27193054 TI - The clinical application of mesenchymal stromal cells in hematopoietic stem cell transplantation. AB - Mesenchymal stromal cells (MSCs) are multipotent stem cells well known for repairing tissue, supporting hematopoiesis, and modulating immune and inflammation response. These outstanding properties make MSCs as an attractive candidate for cellular therapy in immune-based disorders, especially hematopoietic stem cell transplantation (HSCT). In this review, we outline the progress of MSCs in preventing and treating engraftment failure (EF), graft versus-host disease (GVHD) following HSCT and critically discuss unsolved issues in clinical applications. PMID- 27193058 TI - The nitrogen responsive transcriptome in potato (Solanum tuberosum L.) reveals significant gene regulatory motifs. AB - Nitrogen (N) is the most important nutrient for the growth of potato (Solanum tuberosum L.). Foliar gene expression in potato plants with and without N supplementation at 180 kg N ha(-1) was compared at mid-season. Genes with consistent differences in foliar expression due to N supplementation over three cultivars and two developmental time points were examined. In total, thirty genes were found to be over-expressed and nine genes were found to be under-expressed with supplemented N. Functional relationships between over-expressed genes were found. The main metabolic pathway represented among differentially expressed genes was amino acid metabolism. The 1000 bp upstream flanking regions of the differentially expressed genes were analysed and nine overrepresented motifs were found using three motif discovery algorithms (Seeder, Weeder and MEME). These results point to coordinated gene regulation at the transcriptional level controlling steady state potato responses to N sufficiency. PMID- 27193059 TI - Diverse Chemistry of Stable Hydronitrogens, and Implications for Planetary and Materials Sciences. AB - Nitrogen hydrides, e.g., ammonia (NH3), hydrazine (N2H4) and hydrazoic acid (HN3), are compounds of great fundamental and applied importance. Their high pressure behavior is important because of their abundance in giant planets and because of the hopes of discovering high-energy-density materials. Here, we have performed a systematic investigation on the structural stability of N-H system in a pressure range up to 800 GPa through evolutionary structure prediction. Surprisingly, we found that high pressure stabilizes a series of previously unreported compounds with peculiar structural and electronic properties, such as the N4H, N3H, N2H and NH phases composed of nitrogen backbones, the N9H4 phase containing two-dimensional metallic nitrogen planes and novel N8H, NH2, N3H7, NH4 and NH5 molecular phases. Another surprise is that NH3 becomes thermodynamically unstable above ~460 GPa. We found that high-pressure chemistry of hydronitrogens is much more diverse than hydrocarbon chemistry at normal conditions, leading to expectations that N-H-O and N-H-O-S systems under pressure are likely to possess richer chemistry than the known organic chemistry. This, in turn, opens a possibility of nitrogen-based life at high pressure. The predicted phase diagram of the N-H system also provides a reference for synthesis of high-energy-density materials. PMID- 27193060 TI - When your pain signifies my gain: neural activity while evaluating outcomes based on another person's pain. AB - The overlap between pain and reward processing pathways leds researchers to hypothesize that there are interactions between them in the human brain. Two hypotheses have been proposed. The "competition hypothesis" posits that reward can reduce pain-related neural activity and vice versa. The "salience hypothesis" suggests that the motivational salience of pain and reward can be mutually reinforced. However, no study has tested these two hypotheses from temporal perspective as we know. In the present study, pictures depicted other people in painful or non-painful situations were used to indicate the valence of outcomes in a gambling task. The event-related potential results revealed an interaction between another person's pain and outcome valence in multiple time stages. Specifically, the amplitudes of the N1 and P3 were enhanced in the win condition compared with the loss condition when the outcome was indicated by painful picture. This interactions between pain and reward support the salience hypothesis but not the competition hypothesis. The present results provide evidence from human subjects that support the salience hypothesis, which claims that observing other people's pain can enhance the salience of reward. PMID- 27193063 TI - Time course and predictors of use of erectile dysfunction treatment in a Veterans Affairs medical center. AB - The objective of this study was to define the pattern and time course of use of ED treatments in a Veterans Affairs (VA) medical center and to identify clinical or demographic variables that are associated with the use of second- or third line ED treatments. We identified 702 men treated for ED at the Greater Los Angeles Veterans Affairs between 2007 and 2013. We extracted demographics, Charlson co-morbidity score, pertinent surgical/medication history as well as use of ED treatments from medical records. On multivariate analysis, age over 65 (OR 1.83, 95% CI: 1.31-2.56) and Charlson co-morbidity score of 1 (OR 1.77, 95% CI: 1.13-2.77) and 2+ (OR 2.07, 95% CI: 1.28-3.36) were significantly associated with use of medicated urethral suppositories for erection (MUSE)/intracorporal injections (ICI) compared with PDE5i/erection devices. Across all men who used second- or third-line treatments, median time until receiving MUSE was 0.6 years and median time until receiving ICI/implant was 2 years. We conclude that men who will ultimately use more invasive ED treatments, such as men with more co morbidities, tend to have a prolonged treatment course. This information may be incorporated into a shared decision-making model for more efficient treatment of ED. PMID- 27193064 TI - Somatosensory evoked potentials assess the efficacy of circumcision for premature ejaculation. AB - To assess the efficacy and mechanism of circumcision in the treatment of premature ejaculation (PE) with redundant prepuce, we enrolled a total of 81 PE patients who received circumcision. The patients' ejaculatory ability and sexual performances were evaluated before and after circumcision by using questionnaires (Intravaginal ejaculation latency time (IELT), Chinese Index of PE with 5 questions (CIPE-5) and International Index of Erectile function- 5 (IIEF-5)). Furthermore, somatosensory evoked potentials (SEPs) including dorsal nerve (DNSEP) and glans penis (GPSEP) of the patients were also measured. The mean IELTs of preoperation and post operation were 1.10+/-0.55 and 2.48+/-2.03 min, respectively (P<0.001). In addition, the geometric mean IELT after operation was 2.16 min, compared with the baseline 1.07 min before the operation, the fold increase of the IELT was 2.02. Compared with the uncircumcised status, scores of CIPE-5 showed a significant increase after circumcision (P<0.001). The mean latencies (and amplitudes) of GPSEP and DNSEP were 38.1+/-4.0 ms (3.0+/-1.9 uV) and 40.5+/-3.4 ms (2.8+/-1.6 uV) before circumcision, respectively; and 42.8+/ 3.3 ms (2.8+/-1.6 uV) and 40.5+/-4.1 ms (2.4+/-1.2 uV) in the follow-up end point after circumcision. Only the latencies of GPSEP showed significant prolongation before and after circumcision (P<0.001). The ejaculation time improvement after circumcision is so small, and equal to placebo response, therefore it could not be interpreted as a therapeutic method in men with PE. PMID- 27193067 TI - I. Dissociation free energies of drug-receptor systems via non-equilibrium alchemical simulations: a theoretical framework. AB - In this contribution I critically revise the alchemical reversible approach in the context of the statistical mechanics theory of non-covalent bonding in drug receptor systems. I show that most of the pitfalls and entanglements for the binding free energy evaluation in computer simulations are rooted in the equilibrium assumption that is implicit in the reversible method. These critical issues can be resolved by using a non-equilibrium variant of the alchemical method in molecular dynamics simulations, relying on the production of many independent trajectories with a continuous dynamical evolution of an externally driven alchemical coordinate, completing the decoupling of the ligand in a matter of a few tens of picoseconds rather than nanoseconds. The absolute binding free energy can be recovered from the annihilation work distributions by applying an unbiased unidirectional free energy estimate, on the assumption that any observed work distribution is given by a mixture of normal distributions, whose components are identical in either direction of the non-equilibrium process, with weights regulated by the Crooks theorem. I finally show that the inherent reliability and accuracy of the unidirectional estimate of the decoupling free energies, based on the production of a few hundreds of non-equilibrium independent sub-nanosecond unrestrained alchemical annihilation processes, is a direct consequence of the funnel-like shape of the free energy surface in molecular recognition. An application of the technique to a real drug-receptor system is presented in the companion paper. PMID- 27193062 TI - A genome-wide association scan implicates DCHS2, RUNX2, GLI3, PAX1 and EDAR in human facial variation. AB - We report a genome-wide association scan for facial features in ~6,000 Latin Americans. We evaluated 14 traits on an ordinal scale and found significant association (P values<5 * 10(-8)) at single-nucleotide polymorphisms (SNPs) in four genomic regions for three nose-related traits: columella inclination (4q31), nose bridge breadth (6p21) and nose wing breadth (7p13 and 20p11). In a subsample of ~3,000 individuals we obtained quantitative traits related to 9 of the ordinal phenotypes and, also, a measure of nasion position. Quantitative analyses confirmed the ordinal-based associations, identified SNPs in 2q12 associated to chin protrusion, and replicated the reported association of nasion position with SNPs in PAX3. Strongest association in 2q12, 4q31, 6p21 and 7p13 was observed for SNPs in the EDAR, DCHS2, RUNX2 and GLI3 genes, respectively. Associated SNPs in 20p11 extend to PAX1. Consistent with the effect of EDAR on chin protrusion, we documented alterations of mandible length in mice with modified Edar funtion. PMID- 27193065 TI - Comparison of different approaches to the surgical treatment of penile fractures: quicker return to sexual function with longitudinal incisions. AB - The objective of this study was to compare the long-term clinical outcomes from longitudinal incisions and subcoronal circumferential degloving incisions in the surgical treatment of penile fractures. From July 2001 to July 2014, 23 patients were identified with penile fractures. Fourteen patients underwent longitudinal incisions after ultrasound localization; nine patients underwent subcoronal circumferential degloving incisions. Sexual function was evaluated preoperatively and postoperatively using an abridged International Index of Erectile Function (IIEF) questionnaire. The mean (+/-s.d.) operative time was 19.1 (+/-3.9) min in the longitudinal incision group and was 45.1 (+/-6.5) min in the subcoronal circumferential degloving incision group (P<0.05). The mean (+/-s.d.) times required to recover sexual function were 35.6 (+/-6.0) days in the longitudinal incision group and 54.0 (+/-5.8) days in the circumferential incision group (P<0.05). Six months postoperatively, the erectile functions of all cases were comparable to the level preoperatively except three patients. One patient from each group reported symptoms associated with mild ED, but they experienced satisfying sexual orgasms after psychotherapy for 2 months. Another patient's score on the IIEF-5 declined from 25 to 24 points in the circumferential incision group 10 months postoperatively, and this was associated with maintaining an erection after vaginal penetration. In conclusion, the longitudinal incision may allow quicker return to sexual function but not necessarily improved the long term clinical outcomes. Furthermore, postoperative psychosocial nursing and psychotherapy should receive more attention. PMID- 27193068 TI - A decahaem cytochrome as an electron conduit in protein-enzyme redox processes. AB - The decahaem cytochrome MtrC from Shewanella oneidensis MR-1 was employed as a protein electron conduit between a porous indium tin oxide electrode and redox enzymes. Using a hydrogenase and a fumarate reductase, MtrC was shown as a suitable and efficient diode to shuttle electrons to and from the electrode with the MtrC redox activity regulating the direction of the enzymatic reactions. PMID- 27193069 TI - Changes in profile of lipids and adipokines in patients with newly diagnosed hypothyroidism and hyperthyroidism. AB - Changes in profile of lipids and adipokines have been reported in patients with thyroid dysfunction. But the evidence is controversial. The present study aimed to explore the relationships between thyroid function and the profile of lipids and adipokines. A cross-sectional study was conducted in 197 newly diagnosed hypothyroid patients, 230 newly diagnosed hyperthyroid patients and 355 control subjects. Hypothyroid patients presented with significantly higher serum levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDLC), fasting insulin, resistin and leptin than control (p < 0.05). Hyperthyroid patients presented with significantly lower serum levels of high-density lipoprotein cholesterol, LDLC and leptin, as well as higher levels of fasting insulin, resistin, adiponectin and homeostasis model insulin resistance index (HOMA-IR) than control (p < 0.05). Nonlinear regression and multivariable linear regression models all showed significant associations of resistin or adiponectin with free thyroxine and association of leptin with thyroid-stimulating hormone (p < 0.001). Furthermore, significant correlation between resistin and HOMA-IR was observed in the patients (p < 0.001). Thus, thyroid dysfunction affects the profile of lipids and adipokines. Resistin may serve as a link between thyroid dysfunction and insulin resistance. PMID- 27193070 TI - Final rotational state distributions from NO(vi = 11) in collisions with Au(111): the magnitude of vibrational energy transfer depends on orientation in molecule surface collisions. AB - When NO molecules collide at a Au(111) surface, their interaction is controlled by several factors; especially important are the molecules' orientation with respect to the surface (N-first vs. O-first) and their distance of closest approach. In fact, the former may control the latter as N-first orientations are attractive and O-first orientations are repulsive. In this work, we employ electric fields to control the molecules' incidence orientation in combination with rotational rainbow scattering detection. Specifically, we report final rotational state distributions of oriented NO(vi = 11) molecules scattered from Au(111) for final vibrational states between vf = 4 and 11. For O-first collisions, the interaction potential is highly repulsive preventing the close approach and scattering results in high-J rainbows. By contrast, these rainbows are not seen for the more intimate collisions possible for attractive N-first orientations. In this way, we reveal the influence of orientation and the distance of closest approach on vibrational relaxation of NO(vi = 11) in collisions with a Au(111) surface. We also elucidate the influence of steering forces which cause the O-first oriented molecules to rotate to an N-first orientation during their approach to the surface. The experiments show that when NO collides at the surface with the N-atom first, on average more than half of the initial vibrational energy is lost; whereas O-first oriented collisions lose much less vibrational energy. These observations qualitatively confirm theoretical predictions of electronically non-adiabatic NO interactions at Au(111). PMID- 27193072 TI - Synthetic Cannabinoid Receptor Agonists and Antagonists: Implication in CNS Disorders. AB - BACKGROUND: Since the discovery of the cannabinoid receptors, numerous studies associate the endocannabinoid system with several physiological and pathological processes including cancer, appetite, fertility, memory, neuropathic and inflammatory pain, obesity, and neurodegenerative diseases. Over the last two decades, several researches have been dedicated extensively on the cannabinoid receptors ligands since the direct activation of cannabinoid receptors results in several beneficial effects, in the brain and in the periphery. The cannabinoid CB1 and CB2 receptor synthetic ligands reported in this review have been collected by a wide research of scientific literature in particular in public database for patents and clinical trials. The references for patent numbers, clinical trial registry numbers, websites and scientific articles are reported in the reference section. RESULTS: During past years, cannabinoid CB1 and CB2 receptor ligands from plants or lab were rapidly developed and then various new structures were reported to be cannabinoids. However the CB1 receptor ligands have had a limited usefulness due to their psychotropic effects, dependence, and cognitive impairment. On the contrary the development of CB2 receptor ligands has been more productive. Furthermore peripherally restricted agonists as well as CB1 receptor positive or negative allosteric modulators were studied with the aim of eliminating the undesirable CB1 receptor central effects. CONCLUSIONS: The CB1 and CB2 receptor ligands offer several therapeutic opportunities for several CNS related diseases. Based on the scientific literature, this review provides an overview of CB1 and CB2 receptor synthetic ligands obtained from drug research and in particular those synthesized for therapeutic purposes and potential clinical applications for central nervous system disorders. PMID- 27193071 TI - Time to wake up: reactive countermeasures to sleep inertia. AB - Sleep inertia is the period of impaired performance and grogginess experienced after waking. This period of impairment is of concern to workers who are on-call, or nap during work hours, and need to perform safety-critical tasks soon after waking. While several studies have investigated the best sleep timing and length to minimise sleep inertia effects, few have focused on countermeasures especially those that can be implemented after waking (i.e. reactive countermeasures). This structured review summarises current literature on reactive countermeasures to sleep inertia such as caffeine, light, and temperature and discusses evidence for the effectiveness and operational viability of each approach. Current literature does not provide a convincing evidence-base for a reactive countermeasure. Caffeine is perhaps the best option, although it is most effective when administered prior to sleep and is therefore not strictly reactive. Investigations into light and temperature have found promising results for improving subjective alertness; further research is needed to determine whether these countermeasures can also attenuate performance impairment. Future research in this area would benefit from study design features highlighted in this review. In the meantime, it is recommended that proactive sleep inertia countermeasures are used, and that safety-critical tasks are avoided immediately after waking. PMID- 27193074 TI - Axillary web syndrome following granulomatous inflammation after folliculitis. PMID- 27193073 TI - Verbal memory declines more in female patients with Parkinson's disease: the importance of gender-corrected normative data. AB - BACKGROUND: Data on gender-specific profiles of cognitive functions in patients with Parkinson's disease (PD) are rare and inconsistent, and possible disease confounding factors have been insufficiently considered. METHOD: The LANDSCAPE study on cognition in PD enrolled 656 PD patients (267 without cognitive impairment, 66% male; 292 with mild cognitive impairment, 69% male; 97 with PD dementia, 69% male). Raw values and age-, education-, and gender-corrected Z scores of a neuropsychological test battery (CERAD-Plus) were compared between genders. Motor symptoms, disease duration, l-dopa equivalent daily dose, depression - and additionally age and education for the raw value analysis - were taken as covariates. RESULTS: Raw-score analysis replicated results of previous studies in that female PD patients were superior in verbal memory (word list learning, p = 0.02; recall, p = 0.03), while men outperformed women in visuoconstruction (p = 0.002) and figural memory (p = 0.005). In contrast, gender corrected Z scores showed that men were superior in verbal memory (word list learning, p = 0.02; recall, p = 0.02; recognition, p = 0.04), while no difference was found for visuospatial tests. This picture could be observed both in the overall analysis of PD patients as well as in a differentiated group analysis. CONCLUSIONS: Normative data corrected for gender and other sociodemographic variables are relevant, since they may elucidate a markedly different cognitive profile compared to raw scores. Our study also suggests that verbal memory decline is stronger in women than in men with PD. Future studies are needed to replicate these findings, examine the progression of gender-specific cognitive decline in PD and define different underlying mechanisms of this dysfunction. PMID- 27193075 TI - Cross-cultural adaptation of the drug-taking confidence questionnaire drug version for use in Brazil. AB - BACKGROUND: The Drug-Taking Confidence Questionnaire evaluates a drug user's confidence in his or her ability to resist the urge to consume psychoactive substances in high-risk situations. This study's objective was to develop a cross cultural adaptation of the eight-item version of the Drug-Taking Confidence Questionnaire (DTCQ-8) for all drugs except alcohol and to verify its content validity and reliability in a pre-test stage. METHODS: The following steps were taken: (1) implementation of the translation protocol and transcultural adaptation, (2) validation of the adapted content, and (3) assessment of reliability. Nine experts participated in the process of adaptation, and the trial's sample comprised 40 drug users in treatment at a Psychosocial Care Center for Alcohol and Other Drugs (CAPSad). RESULTS: The average indices of semantic agreement (0.989; 0.989; 1.00), idiomatic (0.967), experiential (0.956), conceptual (0.978) and content validity with respect to language clarity (0.972), practice relevance (0.958), theoretical relevance (0.958) and theoretical dimension (1.00) showed that the adaption was successful. The mean total score of the DTCQ-8 version for other drugs was 477.00 + 234.27-SD, and 57.5 % of the users were classified as having moderate self-efficacy to resist the urge to use drugs in high-risk situations. The Cronbach's alpha coefficient was 0.889 for the complete instrument and 0.863-0.890 between items. CONCLUSIONS: The DTCQ-8 version for other drugs proved to be easy to use and understand, and its process of adaptation was satisfactory for use in the Brazilian context. In this sample, the questionnaire was adequate to measure users' self-efficacy to resist the urge to consume these substances in high-risk situations. PMID- 27193076 TI - Perspectives of People Living with HIV on Access to Health Care: Protocol for a Scoping Review. AB - BACKGROUND: Strategies to improve access to health care for people living with human immunodeficiency virus (PLHIV) have demonstrated limited success. Whereas previous approaches have been informed by the views of health providers and decision-makers, it is believed that incorporating patient perspectives into the design and evaluations of health care programs will lead to improved access to health care services. OBJECTIVE: We aim to map the literature on the perspectives of PLHIV concerning access to health care services, to identify gaps in evidence, and to produce an evidence-informed research action plan to guide the Living with HIV program of research. METHODS: This scoping review includes peer-reviewed and grey literature from 1946 to May 2014 using double data extraction. Variations of the search terms "HIV", "patient satisfaction", and "health services accessibility" are used to identify relevant literature. The search strategy is being developed in consultation with content experts, review methodologists, and a librarian, and validated using gold standard studies identified by those stakeholders. The inclusion criteria are (1) the study includes the perspectives of PLHIV, (2) study design includes qualitative, quantitative, or mixed methods, and (3) outcome measures are limited to patient satisfaction, their implied needs, beliefs, and desires in relation to access to health care. The papers are extracted by two independent reviewers, including quality assessment. Data is then collated, summarized, and thematically analyzed. RESULTS: A total of 12,857 references were retrieved, of which 326 documents were identified as eligible in pre-screening, and 64 articles met the inclusion criteria (56% qualitative studies, 38% quantitative studies and 6% mixed-method studies). Only four studies were conducted in Canada. Data synthesis is in progress and full results are expected in June, 2016. CONCLUSIONS: This scoping review will record and characterize the extensive body of literature on perspectives of PLHIV regarding access to health care. A literature repository will be developed to assist stakeholders, decision-makers, and PLHIV in developing and implementing patient oriented health care programs. PMID- 27193078 TI - Development of a novel walkability index for London, United Kingdom: cross sectional application to the Whitehall II Study. AB - BACKGROUND: Physical activity is essential for health; walking is the easiest way to incorporate activity into everyday life. Previous studies report positive associations between neighbourhood walkability and walking but most focused on cities in North America and Australasia. Urban form with respect to street connectivity, residential density and land use mix-common components of walkability indices-differs in European cities. The objective of this study was to develop a walkability index for London and test the index using walking data from the Whitehall II Study. METHODS: A neighbourhood walkability index for London was constructed, comprising factors associated with walking behaviours: residential dwelling density, street connectivity and land use mix. Three models were produced that differed in the land uses included. Neighbourhoods were operationalised at three levels of administrative geography: (i) 21,140 output areas, (ii) 633 wards and (iii) 33 local authorities. A neighbourhood walkability score was assigned to each London-dwelling Whitehall II Study participant (2003 04, N = 3020, mean +/- SD age = 61.0 years +/- 6.0) based on residential postcode. The effect of changing the model specification and the units of enumeration on spatial variation in walkability was examined. RESULTS: There was a radial decay in walkability from the centre to the periphery of London. There was high inter-model correlation in walkability scores for any given neighbourhood operationalisation (0.92-0.98), and moderate-high correlation between neighbourhood operationalisations for any given model (0.39-0.70). After adjustment for individual level factors and area deprivation, individuals in the most walkable neighbourhoods operationalised as wards were more likely to walk >6 h/week (OR = 1.4; 95 % CI: 1.1-1.9) than those in the least walkable. CONCLUSIONS: Walkability was associated with walking time in adults. This walkability index could help urban planners identify and design neighbourhoods in London with characteristics more supportive of walking, thereby promoting public health. PMID- 27193077 TI - Selectivity on-target of bromodomain chemical probes by structure-guided medicinal chemistry and chemical biology. AB - Targeting epigenetic proteins is a rapidly growing area for medicinal chemistry and drug discovery. Recent years have seen an explosion of interest in developing small molecules binding to bromodomains, the readers of acetyl-lysine modifications. A plethora of co-crystal structures has motivated focused fragment based design and optimization programs within both industry and academia. These efforts have yielded several compounds entering the clinic, and many more are increasingly being used as chemical probes to interrogate bromodomain biology. High selectivity of chemical probes is necessary to ensure biological activity is due to an on-target effect. Here, we review the state-of-the-art of bromodomain targeting compounds, focusing on the structural basis for their on-target selectivity or lack thereof. We also highlight chemical biology approaches to enhance on-target selectivity. PMID- 27193080 TI - An open-label randomised controlled trial on the efficacy of adding intranasal fentanyl to intravenous tramadol in patients with moderate to severe pain following acute musculoskeletal injuries. AB - INTRODUCTION: The use of intranasal fentanyl as an alternative type of analgesia has been shown to be effective in paediatric populations and prehospital settings. There are a limited number of studies on the use of intranasal fentanyl in adult patients in emergency settings. METHODS: An open-label study was conducted to evaluate the effectiveness of the addition of 1.5 mcg/kg intranasal fentanyl to 2 mg/kg intravenous tramadol (fentanyl + tramadol arm, n = 10) as compared to the administration of 2 mg/kg intravenous tramadol alone (tramadol only arm, n = 10) in adult patients with moderate to severe pain due to acute musculoskeletal injuries. RESULTS: When analysed using the independent t-test, the difference between the mean visual analogue scale scores pre-intervention and ten minutes post-intervention was 29.8 +/- 8.4 mm in the fentanyl + tramadol arm and 19.6 +/- 9.7 mm in the tramadol-only arm (t[18] = 2.515, p = 0.022, 95% confidence interval 1.68-18.72 mm). A statistically significant, albeit transient, reduction in the ten-minute post-intervention mean arterial pressure was noted in the fentanyl + tramadol arm as compared to the tramadol-only arm (13.35 mmHg vs. 7.65 mmHg; using Mann-Whitney U test with U-value 21.5, p = 0.029, r = 0.48). There was a higher incidence of transient dizziness ten minutes after intervention among the patients in the fentanyl + tramadol arm. CONCLUSION: Although effective, intranasal fentanyl may not be appropriate for routine use in adult patients, as it could result in a significant reduction in blood pressure. PMID- 27193079 TI - Effect of platelet-rich plasma combined with demineralised bone matrix on bone healing in rabbit ulnar defects. AB - INTRODUCTION: This study evaluates the effect of autologous platelet-rich plasma (PRP) combined with xenogeneic demineralised bone matrix (DBM) on bone healing of critical-size ulnar defects (2-2.5 times the ulnar diameter) in New Zealand White rabbits. METHODS: Critical-size defects were created unilaterally in the ulna of 36 rabbits, while keeping the contralateral limb intact. They were divided into three groups. In Group A, the defect was filled with autologous PRP and in Group B, with autologous PRP combined with DBM; in Group C, the defect remained empty. The rabbits were euthanised 12 weeks postoperatively. Radiological, biomechanical and histological assessments were carried out and statistical analysis of the results was performed. RESULTS: Group B had significantly higher radiological and histological scores than Groups A and C. Defects in Group B showed significant new bone formation, whereas there was minimal or no new bone formation in Groups A and C. Only specimens in Group B showed macroscopic bone union. Biomechanical evaluation of the treated and intact contralateral limbs in Group B showed significant differences. CONCLUSION: In this study, statistically significant enhancement of bone healing was found in critical-size defects treated with PRP and DBM, as shown by radiological findings, gross assessment, and biomechanical and histopathological results. Defects in the two other groups remained unbridged. Therefore, PRP was effective only when it was used in combination with a bone graft. PMID- 27193081 TI - Percutaneous transcatheter aortic valve implantation for degenerated surgical bioprostheses: the first case series in Asia with one-year follow-up. AB - INTRODUCTION: Percutaneous transcatheter aortic valve implantation (TAVI) has become an established therapy for inoperable and high-surgical-risk patients with severe aortic stenosis. Although TAVI in patients with degenerated surgical aortic bioprostheses (i.e. valve-in-valve TAVI) is increasingly reported in Western studies, such data is lacking in Asian patients. We describe the initial experience of valve-in-valve TAVI in Asia. METHODS: Eight patients who underwent valve-in-valve TAVI due to degenerated aortic bioprostheses were enrolled. The mechanism of bioprosthetic valve failure was stenotic, regurgitation or mixed. All procedures were performed via transfemoral arterial access, using the self expanding CoreValve prosthesis or balloon-expandable SAPIEN XT prosthesis. RESULTS: The mean age of the patients was 71.6 +/- 13.2 years and five were male. Mean duration to surgical bioprosthesis degeneration was 10.2 +/- 4.1 years. Valve-in-valve TAVI was successfully performed in all patients. CoreValve and SAPIEN XT prostheses were used in six and two patients, respectively. There were no deaths, strokes or permanent pacemaker requirement at 30 days, with one noncardiac mortality at one year. All patients experienced New York Heart Association functional class improvement. Post-procedure mean pressure gradients were 20 +/- 11 mmHg and 22 +/- 8 mmHg at 30 days and one year, respectively. Residual aortic regurgitation (AR) of more than mild severity occurred in one patient at 30 days. At one year, only one patient had mild residual AR. CONCLUSION: In our experience of valve-in-valve TAVI, procedural success was achieved in all patients without adverse events at 30 days. Good clinical and haemodynamic outcomes were sustained at one year. PMID- 27193082 TI - Nanoshell-Enhanced Raman Spectroscopy on a Microplate for Staphylococcal Enterotoxin B Sensing. AB - A sensitive surface-enhanced Raman scattering (SERS) immunosensor based on the Au nanoparticle (Au NP) shell structure was developed to detect staphylococcal enterotoxin B (SEB) on a microplate. Au NPs modified with 4-nitrothiophenol (4 NTP) and coated with Ag shell of controlled thickness at 6.6 nm exhibited excellent SERS intensity and were used as signal reporters in the detection of SEB. The engaged 4-NTP allowed the significant electromagnetic enhancement between Au NPs and the Ag shell and prevented the dissociation of the Raman reporter. More importantly, 4-NTP-differentiated SERS signals between the sample and microplate. The SERS-based immunosensor had a limit of detection of 1.3 pg/mL SEB. Analysis of SEB-spiked milk samples revealed that the developed method had high accuracy. Therefore, the SERS-encoded Au@Ag core-shell structure-based immunosensor is promising for the detection of biotoxins, pathogens, and environmental pollutants. PMID- 27193083 TI - Critical residues involved in tau binding to fyn: implications for tau phosphorylation in Alzheimer's disease. AB - Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterised by neuropathological deposits of amyloid plaques and neurofibrillary tangles comprised of beta-amyloid and tau protein, respectively. In AD, tau becomes abnormally phosphorylated and aggregates to form intracellular deposits. However, the mechanisms by which tau exerts neurotoxicity in disease remain unclear. Recent studies have suggested that the presence of tau at synapses may indicate a role in neuronal signalling, which could be disrupted in pathological conditions. The non-receptor-associated tyrosine kinase fyn is located at the dendrite in neurons, where it was recently shown to interact with tau to stabilise receptor complexes at the post-synaptic density. Fyn also co localises with tau in a proportion of neurons containing tau tangles in AD and fyn is also a tau kinase. Hence, tau-fyn interactions could play a pathogenic role in AD. Here we report the identification of critical proline residues, Pro213, Pro216, and Pro219, located within the fifth and sixth Pro-X-X-Pro motifs in the proline-rich region of tau, that are important for its binding to fyn. These residues in tau are flanked by numerous phosphorylation sites and therefore we investigated the relationship between fyn and the degree of tau phosphorylation in human post-mortem brain tissue. We found no difference in the amount of fyn present in control and AD brain. Notably, however, there was a significant correlation between fyn and phosphorylated tau at specific phospho epitopes in control, but not in AD brain. Our results suggest that the pathological mechanisms underlying AD, that result in increased tau phosphorylation, may disrupt the physiological relationship between tau phosphorylation and fyn. PMID- 27193085 TI - The Unsuitability of Energy Expenditure Derived From Microtechnology for Assessing Internal Load in Collision-Based Activities. AB - This aim of this study was to examine the validity of energy expenditure derived from microtechnology when measured during a repeated-effort rugby protocol. Sixteen male rugby players completed a repeated-effort protocol comprising 3 sets of 6 collisions during which movement activity and energy expenditure (EEGPS) were measured using microtechnology. In addition, energy expenditure was estimated from open-circuit spirometry (EEVO2). While related (r = .63, 90%CI .08 .89), there was a systematic underestimation of energy expenditure during the protocol (-5.94 +/- 0.67 kcal/min) for EEGPS (7.2 +/- 1.0 kcal/min) compared with EEVO2 (13.2 +/- 2.3 kcal/min). High-speed-running distance (r = .50, 95%CI -.66 to .84) was related to EEVO2, while PlayerLoad was not (r = .37, 95%CI -.81 to .68). While metabolic power might provide a different measure of external load than other typically used microtechnology metrics (eg, high-speed running, PlayerLoad), it underestimates energy expenditure during intermittent team sports that involve collisions. PMID- 27193084 TI - Decreased microRNA-452 expression and its prognostic significance in human osteosarcoma. AB - BACKGROUND: MicroRNA-452 (miR-452) was previously reported to be dysregulated in several types of human cancers and involved in tumor progression. The aim of this study was to investigate the clinical significance and prognostic value of miR 452 expression in human osteosarcoma. METHODS: The expression of miR-452 was detected in 95 pairs of osteosarcoma specimens and adjacent noncancerous bone tissues using quantitative RT-PCR (qRT-PCR) assay. Then, the association of miR 452 levels with clinicopathological features and prognosis was analyzed. The roles of miR-452 in regulating osteosarcoma cell proliferation, apoptosis, and invasion were evaluated in vitro. RESULTS: miR-452 expression was significantly downregulated in osteosarcoma tissues than those in corresponding noncancerous bone tissues (P < 0.001). Decreased miR-452 expression was linked to larger tumor size, high tumor grade, advanced clinical stage, distant metastasis, and shorter overall survival. Multivariate Cox regression analysis confirmed that low level of miR-452 expression predicted poor prognosis independently. miR-452 overexpression in MG-63 cells suppressed cell proliferation, promoted cell apoptosis, inhibited cell invasion, and led to decreased BMI1 protein levels. CONCLUSIONS: These findings suggest that miR-452 downregulation may be involved in osteosarcoma formation and progression and that miR-452 would serve as a novel prognostic biomarker for patients with this disease. PMID- 27193087 TI - The Matter of Urgency. PMID- 27193086 TI - Conceptual Analysis for Nanoscience. PMID- 27193089 TI - Tribute to Ronnie Kosloff. PMID- 27193088 TI - Two Spin-State Reactivity in the Activation and Cleavage of CO2 by [ReO2](.). AB - The rhenium dioxide anion [ReO2](-) reacts with carbon dioxide in a linear ion trap mass spectrometer to produce [ReO3](-) corresponding to activation and cleavage of a C-O bond. Isotope labeling experiments using [Re(18)O2](-) reveal that (18)O/(16)O scrambling does not occur prior to cleavage of the C-O bond. Density functional theory calculations were performed to examine the mechanism for this oxygen atom abstraction reaction. Because the spins of the ground states are different for the reactant and product ions ((3)[ReO2](-) versus (1)[ReO3]( )), both reaction surfaces were examined in detail and multiple [O2Re-CO2](-) intermediates and transition structures were located and minimum energy crossing points were calculated. The computational results show that the intermediate [O2Re(eta(2)-C,O-CO2)](-) species most likely initiates C-O bond activation and cleavage. The stronger binding affinity of CO2 within this species and the greater instabilities of other [O2Re-CO2)](-) intermediates are significant enough that oxygen atom exchange is avoided. PMID- 27193093 TI - Periostin promotes immunosuppressive premetastatic niche formation to facilitate breast tumour metastasis. AB - Periostin (POSTN) is a limiting factor in the metastatic colonization of disseminated tumour cells. However, the role of POSTN in regulating the immunosuppressive function of immature myeloid cells in tumour metastasis has not been documented. Here, we demonstrate that POSTN promotes the pulmonary accumulation of myeloid-derived suppressor cells (MDSCs) during the early stage of breast tumour metastasis. Postn deletion decreases neutrophil and monocytic cell populations in the bone marrow of mice and suppresses the accumulation of MDSCs to premetastatic sites. We also found that POSTN-deficient MDSCs display reduced activation of ERK, AKT and STAT3 and that POSTN deficiency decreases the immunosuppressive functions of MDSCs during tumour progression. Moreover, the pro metastatic role of POSTN is largely limited to ER-negative breast cancer patients. Lysyl oxidase contributes to POSTN-promoted premetastatic niche formation and tumour metastasis. Our findings indicate that POSTN is essential for immunosuppressive premetastatic niche formation in the lungs during breast tumour metastasis and is a potential target for the prevention and treatment of breast tumour metastasis. Copyright (c) 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID- 27193095 TI - Identification of confounder in epidemiologic data contaminated by measurement error in covariates. AB - BACKGROUND: Common methods for confounder identification such as directed acyclic graphs (DAGs), hypothesis testing, or a 10 % change-in-estimate (CIE) criterion for estimated associations may not be applicable due to (a) insufficient knowledge to draw a DAG and (b) when adjustment for a true confounder produces less than 10 % change in observed estimate (e.g. in presence of measurement error). METHODS: We compare previously proposed simulation-based approach for confounder identification that can be tailored to each specific study and contrast it with commonly applied methods (significance criteria with cutoff levels of p-values of 0.05 or 0.20, and CIE criterion with a cutoff of 10 %), as well as newly proposed two-stage procedure aimed at reduction of false positives (specifically, risk factors that are not confounders). The new procedure first evaluates potential for confounding by examination of correlation of covariates and applies simulated CIE criteria only if there is evidence of correlation, while rejecting a covariate as confounder otherwise. These approaches are compared in simulations studies with binary, continuous, and survival outcomes. We illustrate the application of our proposed confounder identification strategy in examining the association of exposure to mercury in relation to depression in the presence of suspected confounding by fish intake using the National Health and Nutrition Examination Survey (NHANES) 2009-2010 data. RESULTS: Our simulations showed that the simulation-determined cutoff was very sensitive to measurement error in exposure and potential confounder. The analysis of NHANES data demonstrated that if the noise-to-signal ratio (error variance in confounder/variance of confounder) is at or below 0.5, roughly 80 % of the simulated analyses adjusting for fish consumption would correctly result in a null association of mercury and depression, and only an extremely poorly measured confounder is not useful to adjust for in this setting. CONCLUSIONS: No a prior criterion developed for a specific application is guaranteed to be suitable for confounder identification in general. The customization of model-building strategies and study designs through simulations that consider the likely imperfections in the data, as well as finite-sample behavior, would constitute an important improvement on some of the currently prevailing practices in confounder identification and evaluation. PMID- 27193094 TI - Overexpression of CTNND1 in hepatocellular carcinoma promotes carcinous characters through activation of Wnt/beta-catenin signaling. AB - BACKGROUND: Increasing evidence supports the association of CTNND1 with tumor development and progression. However, the mechanism and clinical significance of CTNND1 deregulation in hepatocellular carcinoma (HCC) remains unknown. In this study, we aim to investigate the role of CTNND1 in HCC. METHODS: qRT-PCR and immunohistochemical analyses were used to measure the levels of CTNND1 in HCC specimens and HCC cell lines. CTNND1 and shCTNND1 were transfected into HCC cell lines to investigate its role in HCC. Cell migration and invasion were measured by Transwell and Matrigel analyses in vitro. In vivo metastasis assays were performed in SCID mice. RESULTS: In clinical HCC samples, we found that CTNND1 expression was significantly up-regulated in cancer lesions compared with paired normal liver tissues. By silencing or overexpressing CTNND1 in HCC cells, we found that CTNND1 could promote cell proliferation, migration, and invasion in vitro. An in-vivo assay showed that CTNND1 dramatically promoted HCC cell tumor formation and metastasis. Moreover, CTNND1 promoted HCC metastasis, at least in part, by indirectly enhancing Wnt/beta-catenin signaling. Consistent with these results, the expression of CTNND1 was positively correlated with beta-catenin, WNT11, Cyclin D1, and BMP7 expression in human HCC specimens. CONCLUSIONS: Our study provides evidence that CTNND1 functions as a novel tumor oncogene in HCC, and may be a potential therapeutic target for HCC management. PMID- 27193096 TI - Identifying novel therapeutic agents using xenograft models of pediatric cancer. AB - In the USA, the overall cure rate for all childhood cancers is seventy percent, and in many patients that ultimately fail curative therapy, initial responses to current multimodality treatments (surgery, radiation therapy and chemotherapy) is good, with overall 5-year event-free survival approaching 80 %. However, current approaches to curative therapy result in significant morbidity and long-term sequelae, including cardiac dysfunction and cognitive impairment. Furthermore, dose-intensive chemotherapy with conventional agents has not significantly improved outcomes for patients that present with advanced or metastatic disease. Classical cytotoxic agents remain the backbone for curative therapy of both hematologic and solid tumors of childhood. While 'molecularly' targeted agents have shown some clinical activity, responses are often modest and of short duration; hence, there is a need to identify new classes of cytotoxic agent that are effective in patients at relapse and that have reduced or different toxicity profiles to normal tissues. Here we review the pediatric preclinical testing program experience of testing novel agents, and the value and limitations of preclinical xenograft models and genetically engineered mouse models for developing novel agents for treatment of childhood cancer. PMID- 27193098 TI - Cell death patterns in Arabidopsis cells subjected to four physiological stressors indicate multiple signalling pathways and cell cycle phase specificity. AB - Corpse morphology, nuclear DNA fragmentation, expression of senescence-associated genes (SAG) and cysteine protease profiles were investigated to understand cell death patterns in a cell cycle-synchronised Arabidopsis thaliana cell suspension culture treated with four physiological stressors in the late G2 phase. Within 4 h of treatment, polyethylene glycol (PEG, 20 %), mannose (100 mM) and hydrogen peroxide (2 mM) caused DNA fragmentation coinciding with cell permeability to Evans Blue (EB) and produced corpse morphology corresponding to apoptosis-like programmed cell death (AL-PCD) with cytoplasmic retraction from the cell wall. Ethylene (8 mL per 250-mL flask) caused permeability of cells to EB without concomitant nuclear DNA fragmentation and cytoplasmic retraction, suggesting necrotic cell death. Mannose inducing glycolysis block and PEG causing dehydration resulted in relatively similar patterns of upregulation of SAG suggesting similar cell death signalling pathways for these two stress factors, whereas hydrogen peroxide caused unique patterns indicating an alternate pathway for cell death induced by oxidative stress. Ethylene did not cause appreciable changes in SAG expression, confirming necrotic cell death. Expression of AtDAD, BoMT1 and AtSAG2 genes, previously shown to be associated with plant senescence, also changed rapidly during AL-PCD in cultured cells. The profiles of nine distinct cysteine protease-active bands ranging in size from ca. 21.5 to 38.5 kDa found in the control cultures were also altered after treatment with the four stressors, with mannose and PEG again producing similar patterns. Results also suggest that cysteine proteases may have a role in necrotic cell death. PMID- 27193097 TI - A prospective, multicenter phase I/II study of induction chemotherapy with docetaxel, cisplatin and fluorouracil (DCF) followed by chemoradiotherapy in patients with unresectable locally advanced esophageal carcinoma. AB - PURPOSE: Standard care for unresectable locally advanced esophageal squamous cell carcinoma (ESCC) is concurrent chemoradiotherapy, but survival remains limited. Neoadjuvant chemotherapy with docetaxel, cisplatin and fluorouracil (DCF) has demonstrated promising activity, with a pathological complete response (CR) of 17 % for resectable stage II/III ESCC. Here, we conducted a multicenter study to assess the efficacy and safety of induction chemotherapy with DCF followed by CRT in patients with unresectable locally advanced ESCC. METHODS: Eligibility criteria included clinical T4 and/or M1 lymph node ESCC, PS 0-1 and age 20-70 years. Treatment consisted of docetaxel 70 mg/m(2) and cisplatin 70 mg/m(2) on day 1, and fluorouracil 750 mg/m(2) on days 1-5, repeated every 3 weeks for three cycles, followed by cisplatin 70 mg/m(2) on days 64 and 92, and fluorouracil 700 mg/m(2) on days 64-67 and 92-95, concurrently with radiotherapy (60 Gy in 30 fractions, 5 days/week). Primary endpoint of the phase II part was CR rate. RESULTS: Thirty-three patients were enrolled. The completion rate of protocol treatment was 88 %. Thirteen patients (39.4 %) achieved a CR. With a median follow-up period of 41 months (range 24-49 months), median progression-free survival was 12.2 months, and median survival was 26.0 months, with a survival rate of 40.4 % at 3 years. The most common grade 3 or 4 toxicities were neutropenia, leukopenia, anorexia and dysphagia. No treatment-related death was observed. CONCLUSION: Induction chemotherapy with DCF followed by CRT is tolerable and shows promising efficacy for unresectable locally advanced ESCC. PMID- 27193099 TI - Prediction and validation of cis-regulatory elements in 5' upstream regulatory regions of lectin receptor-like kinase gene family in rice. AB - Lectin receptor-like kinases (LecRLKs) play crucial roles in regulating plant growth and developmental processes in response to stress. In transcriptional gene regulation for normal cellular functions, cis-acting regulatory elements (CREs) direct the temporal and spatial gene expression with respect to environmental stimuli. A complete insightful of the transcriptional gene regulation system relies on effective functional analysis of CREs. Here, we analyzed the potential putative CREs present in the promoters of rice LecRLKs genes by using PlantCARE database. The CREs in LecRLKs promoters are associated with plant growth/development, light response, plant hormonal regulation processes, various stress responses, hormonal response like ABA, root-specific expression responsive, drought responsive, and cell and organ specific regulatory elements. The effect of methylation on these cis-regulatory elements was also analyzed. Real-time analysis of rice seedling under various stress conditions showed the expression levels of selected LecRLK genes superimposing the number of different CREs present in 5' upstream region. The overall results showed that the possible CREs function in the selective expression/regulation of LecRLKs gene family and during rice plant development under stress. PMID- 27193100 TI - SmLEA2, a gene for late embryogenesis abundant protein isolated from Salvia miltiorrhiza, confers tolerance to drought and salt stress in Escherichia coli and S. miltiorrhiza. AB - Abiotic stresses, such as drought and high salinity, are major factors that limit plant growth and productivity. Late embryogenesis abundant (LEA) proteins are members of a diverse, multigene family closely associated with tolerance to abiotic stresses in numerous organisms. We examined the function of SmLEA2, previously isolated from Salvia miltiorrhiza, in defense responses to drought and high salinity. Phylogenetic analysis indicated that SmLEA2 belongs to the LEA_2 subfamily. Its overexpression in Escherichia coli improved growth performance when compared with the control under salt and drought stresses. We further characterized its roles in S. miltiorrhiza through overexpression and RNAi mediated silencing. In response to drought and salinity treatments, transgenic plants overexpressing SmLEA2 exhibited significantly increased superoxide dismutase activity, reduced levels of lipid peroxidation, and more vigorous growth than empty-vector control plants did. However, transgenic lines in which expression was suppressed showed the opposite results. Our data demonstrate that SmLEA2 plays an important role in the abiotic stress response and its overexpression in transgenic S. miltiorrhiza improves tolerance to excess salt and drought conditions. PMID- 27193101 TI - [Strategies for the noninvasive diagnosis of melanoma]. AB - The diagnosis of advanced cutaneous melanoma may easily be made by the unaided eye, followed by excisional biopsy and histopathological examination. However, in the setting of melanoma screening examinations in high-risk patients with many nevi, dermatologists are challenged with the differentiation of atypical but benign nevi and early invasive or in situ melanomas. In this situation, there is a real need for additional, noninvasive examination techniques that may serve as an aide to decide for or against an excisional biopsy. Conventional dermoscopy is a well-established examination procedure and an increase in sensitivity was confirmed by two independent meta-analyses. Moreover, dynamic changes or newly developed pigmented lesions may be detected by sequential digital dermoscopy or (automated) total body photography, respectively. Over the past years, a number of medicinal products gained market access after licensing by American and European agencies for the noninvasive diagnosis of cutaneous neoplasms. These devices are based on technologies including in vivo reflectance confocal microscopy, multispectral analysis, electrical impedance spectroscopy, or Raman spectroscopy. Other technologies are still on the verge of becoming less experimental but more clinically applicable for diagnosing melanoma (in vivo multiphoton tomography, stepwise two-photon laser spectroscopy, infrared thermal image analysis, epidermal genetic information retrieval). This review provides a concise overview of general principles and sheds light on indication and added value for dermatologists. PMID- 27193102 TI - Masked hypertension in newly diagnosed hypothyroidism: a pilot study. AB - PURPOSE: Masked hypertension (MH) is the association of normal office blood pressure (BP) with high ambulatory or home BP. This condition is associated with increased cardiovascular target organ damage, as true hypertension. Because the relation with hypothyroidism is controversial, we investigated it in a pilot longitudinal and controlled study. METHODS: We consecutively enrolled 64 newly diagnosed hypothyroid patients, 38 subclinical (s-HYPO), and 26 overt (o-HYPO). The control group consisted of 50 euthyroid subjects seen at outpatient clinics. All participants underwent office and 24-h ambulatory BP measurement. RESULTS: BP monitoring revealed a higher prevalence of MH both in s-HYPO (26.3 %) and in o HYPO (15.4 %) than in euthyroid subjects (10 %, p = 0.05); true hypertension also was more frequent in o-HYPO (11.5 %) and s-HYPO (10.5 %) than in controls (8 %, p = 0.03). The odds ratio for hypertension versus normotension confirmed a significantly increased risk of MH in hypothyroid patients versus euthyroid subjects (3.29, 1.08-10.08; p = 0.02). In a subgroup of patients reevaluated after restoration of euthyroidism, an improvement of BP profile was observed, especially in s-HYPO subgroup, with a decreased prevalence of MH (from 25 to 10.7 %) and true hypertension (from 10.7 to 3.4 %). CONCLUSIONS: Hypothyroidism may be an important predictor of higher BP values, with an increased risk of MH. Because MH is a cardiovascular risk and can be reversed by thyroid hormone replacement, its presence should represent an indication for thyroid hormone replacement therapy also in patients with s-HYPO. PMID- 27193103 TI - Long Noncoding RNA-Sox2OT Knockdown Alleviates Diabetes Mellitus-Induced Retinal Ganglion Cell (RGC) injury. AB - Retinal ganglion cell (RGC) injury is one of the important pathological features of diabetes-induced retinal neurodegeneration. Increasing attention has been paid to find strategies for protecting against RGC injury. Long noncoding RNAs (lncRNAs) have emerged as the key regulators of many cell functions. Here, we show that Sox2OT expression is significantly down-regulated in the retinas of STZ induced diabetic mice and in the RGCs upon high glucose or oxidative stress. SOX2OT knockdown protects RGCs against high glucose-induced injury in vitro. Moreover, Sox2OT knockdown plays a neuroprotective role in diabetes-related retinal neurodegeneration in vivo. Sox2OT knockdown could regulate oxidative stress response in RGCs and diabetic mouse retinas. Sox2OT knockdown plays an anti-oxidative role via regulating NRF2/HO-1 signaling activity. Taken together, Sox2OT knockdown may be a therapeutic strategy for the prevention and treatment of diabetes-induced retinal neurodegeneration. PMID- 27193104 TI - Enduring large use of acetaminophen suppositories for fever management in children: a national survey of French parents and healthcare professionals' practices. AB - The pharmacological specificities of the rectal formulation of acetaminophen led to a debate on its appropriateness for managing fever in children, but few data are available on the formulation's current use and determinants of use. In a national cross-sectional study between 2007 and 2008, healthcare professionals were asked to include five consecutive patients with acute fever. Among the 6255 children (mean age 4.0 years +/- 2.8 SD) who received acetaminophen given by parents or prescribed/recommended by healthcare professionals, determinants of suppository use were studied by multilevel models. A suppository was given by 27 % of parents and prescribed/recommended by 19 % of healthcare professionals, by 24 and 16 %, respectively, for children 2 to 5 years old, and by 13 and 8 %, respectively, for those 6 to 12 years old. Among children who received suppositories from parents and healthcare professionals, 83 and 84 %, respectively, did not vomit. Suppository use was independently associated with several patient- and healthcare professional-level characteristics: young age of children, presence of vomiting, or lack of diarrhea. CONCLUSION: We report an enduring large use of suppositories in France for the symptomatic management of fever in children, including in non-vomiting and/or older children. The rational for such use should be questioned. WHAT IS KNOWN: * The pharmacological specificities of the rectal formulation of acetaminophen have led to a debate on its appropriateness for managing fever in children. Few data are available on the formulation's current use and determinants of the use. What is New: * In a national cross-sectional study, we observed a large use of suppositories in France for symptomatic management of fever in children. Suppositories were frequently used for the youngest children but also for older and/or non-vomiting children. PMID- 27193105 TI - Association between IL-6 Gene (-174 & -572 G/C) Polymorphisms and Endometrial Adenocarcinoma Risk. AB - We aimed to evaluate the association of IL-6 gene polymorphisms at positions of 174 and -572 and predisposition of endometrial adenocarcinoma (EAC) in a Chinese population. EAC patients have remarkably higher frequency of IL-6 -174 CC genotype [odds ratio (OR) =1.56, 95 % confidence interval (CI) =1.07-2.23; P = 0.03], IL-6 -572 CC genotype (OR =1.93, 95%CI =1.17-3.15; P = 0.01) and IL-6 -174 C allele (OR =1.22, 95 % CI =1.03-1.46; P = 0.04) compared with healthy controls. When stratified with FIGO stage, patients with III-IV EAC have a significantly higher frequency of IL-6 -174 CC genotype (OR =1.66, 95% CI =1.06-2.58; P = 0.02) than healthy controls. The CC genotype of IL-6 gene polymorphisms at positions of -174 and -572 may denote potential high risk of EAC. PMID- 27193107 TI - HOW DO PATIENTS EXPERIENCE A KIDNEY BIOPSY? AB - BACKGROUND: Guidelines for care before, during and after a kidney biopsy vary nationally and internationally. A literature search has shown few studies about the care before, during and after a kidney biopsy and we found one study from the patients' perspective. OBJECTIVES: The aim of the study is to gain knowledge about patients' experiences before, during and after a kidney biopsy. METHODS: A qualitative study with a phenomenological and hermeneutic approach using 'observiews' of seven patients before, during and after a kidney biopsy. Data were analysed using Malterud's principles of systematic text condensation. RESULTS: Three themes were found: The patients' basic needs, the patient's needs for information and the patients use humour as a coping strategy. CONCLUSION AND APPLICATION TO PRACTICE: The patients' experiences were characterised by their need to fulfill self-care requirements, because they had to lie down for four to six hours after the biopsy procedure. There is a need to find evidence for the time the patient need to be bedbound to avoid bleeding complications. The patients' needs for information were different, which explains why information should be individualised. There is particular need for more information after discharge. PMID- 27193108 TI - Rats respond where it counts. AB - Taniuchi, Sugihara, Wakashima, and Kamijo (2016) report the surprising finding that rats can transfer numerical discrimination to novel objects. Further experiments show that rat numerical discrimination is flexible, as it can both count homogeneous and heterogeneous objects and omit an odd object. PMID- 27193106 TI - Prognostic Factors for Morbimortality in Sleeve Gastrectomy. The Importance of the Learning Curve. A Spanish-Portuguese Multicenter Study. AB - BACKGROUND: Complications in sleeve gastrectomy (SG) can cast a shadow over the technique's good results and compromise its safety. The aim of this study is to identify risk factors for complications, and especially those that can potentially be modified to improve safety. METHODS: A retrospective multicenter cohort study was carried out, involving the participation of 29 hospitals. Data was collected on demographic variables, associated comorbidities, technical modifications, the surgeon's experience, and postoperative morbimortality. A multivariate logistic regression analysis was carried out on risk factors (RFs) for the complications of leak/fistula, hemoperitoneum, pneumonia, pulmonary embolism, and death. RESULTS: The following data were collected for 2882 patients: age, 43.85 +/- 11.6. 32.9 % male; BMI 47.22 +/- 8.79; 46.2 % hypertensive; 29.2 % diabetes2; 18.2 % smokers; bougie calibre >=40 F 11.1 %; complications 11.7 % (2.8 % leaks, 2.7 % hemoperitoneum, 1.1 % pneumonia, 0.2 % pulmonary embolism); and death 0.6 %. RFs for complications were as follows: surgeon's experience < 20 patients, OR 1.72 (1.32-2.25); experience > 100 patients, OR 0.78 (0.69-0.87); DM2, OR1.48(1.12-1.95); probe > 40 F, OR 0.613 (0.429-0.876). Leak RFs were the following: smoking, OR1.93 (1.1-3.41); surgeon's experience < 20 patients, OR 2.4 (1.46-4.16); experience of 20-50 patients, OR 2.5 (1.3-4.86); experience >100 patients, OR 0.265 (0.11-0.63); distance to pylorus > 4 cm, OR 0.510 (0.29-0.91). RFs for death were as follows: smoking, OR 8.64 (2.63-28.34); DM2, OR 3.25 (1.1-9.99); distance to pylorus < 5 cm, OR 6.62 (1.63-27.02). CONCLUSIONS: The safety of SG may be compromised by nonmodifiable factors such as age >65, patient comorbidities (DM2, hypertension), and prior treatment with anticoagulants, as well as by modifiable factors such as smoking, bougie size <40 F, distance to the pylorus <4 cm, and the surgeon's experience (<50-100 cases). PMID- 27193109 TI - Cardioprotective effect of resveratrol analogue isorhapontigenin versus omega-3 fatty acids in isoproterenol-induced myocardial infarction in rats. AB - Myocardial infarction (MI) is a common cause of mortality worldwide. Isorhapontigenin is a derivative of stilbene with chemical structure similar to resveratrol. The omega-3 fatty acids (FA) have beneficial effects on neurodegenerative, inflammatory, and cardiovascular diseases. The aim of this study was to investigate the effects of pretreatment with isorhapontigenin and omega-3 FA on rat model of isoproterenol-induced MI. Fifty-six rats were divided into seven groups: normal, normal + isorhapontigenin, normal + omega-3 FA, MI, MI + isorhapontigenin, MI + omega-3 FA, and MI + isorhapontigenin + omega-3 FA. Serum levels of cardiac marker enzymes [lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB)], cardiac troponin I (cTnI), inflammatory markers [tumor necrosis factor-alpha (TNF-alpha) and interleukin-6], and lipid profile [triglycerides, total cholesterol (T.Ch), high and low density lipoproteins (HDL, LDL), and phospholipids] as well as cardiac levels of malondialdehyde and anti oxidants [reduced glutathione (GSH), superoxide dismutase (SOD), and catalase)] were measured in all rats. ECG and histopathological examination were performed. Isoproterenol caused a significant elevation of ST segment, decreased R wave amplitude, HDL, and anti-oxidants, and increased LDH, CK-MB, cTnI, TNF-alpha, interleukin-6, malondialdehyde, triglycerides, T.Ch, LDL, and phospholipids. Omega-3 FA or isorhapontigenin significantly decreased the ST segment elevation, LDH, CK-MB, cTnI, TNF-alpha, interleukin-6, malondialdehyde, and phospholipids and increased R wave amplitude and anti-oxidants. The effects of combined omega-3 FA and isorhapontigenin were more significant than either of them alone. Therefore, we conclude that omega-3 FA and isorhapontigenin have a cardioprotective effect on rats with isoproterenol-induced MI through their anti oxidant and anti-inflammatory actions. PMID- 27193110 TI - The development of sweet taste: From biology to hedonics. AB - From the age of 2 years, an American child is more likely to consume a sugar sweetened product than a fruit or vegetable on any given day-a troubling statistic, given that food preferences are established early in childhood, as well as the strong association between this dietary pattern and increased risk of developing a number of chronic diseases. Here, we review the ontogeny and biopsychology of sweet taste, highlighting how a biological drive to prefer sweetness at high concentrations during childhood, which would have conferred an advantage in environments of scarcity, now predisposes children to overconsume all that is sweet in a modern food system replete with added sugars. We review the power of sweet taste to blunt expressions of pain and mask bad tastes in foods as well as factors that predispose some to consume high-sugar diets, including experiential learning and taste preferences driven in part by genetics. Understanding children's unique vulnerability to our current food environment, rich in both nutritive and nonnutritive sweeteners, is highlighted as a priority for future research to develop evidence-based strategies to help establish healthy dietary behaviors early in life. PMID- 27193112 TI - Urinary proteomic pattern in female stress urinary incontinence: a pilot study. AB - INTRODUCTION AND HYPOTHESIS: Previous studies aiming to identify specific pre defined urine protein biomarkers for stress urinary incontinence (SUI) have not identified clinically important differences. The hypothesis of our study was that the global distribution of urinary proteins, the proteome, differs between women with and those without SUI. METHODS: In this age-matched case-control study, we compared the urinary proteome of 20 women with SUI and 20 controls. Proteins were identified by applying high-performance liquid chromatography separation and tandem mass spectrometry detection. Data analysis was performed using Mascot 2.4.1 embedded in ProteinScape 3.1. RESULTS: We identified 828 different proteins. The concentration of six of those showed a significant difference between urine samples of SUI patients and those of controls (q value < 0.25). Four proteins showed a higher abundance in SUI samples compared with controls: plasma serine protease inhibitor (logFC 1.11), leucine-rich alpha-2-glycoprotein (logFC 3.91), lysosomal alpha-glucosidase (logFC 1.24), and peptidyl-prolyl cis- trans isomerase A (logFC 1.96). We identified two proteins in lower abundance in SUI samples compared with controls: uromodulin (logFC -4.87) and TALPID3 (logFC 1.99). CONCLUSIONS: Overexpression of plasma serine protease inhibitor, leucine rich alpha-2-glycoprotein, lysosomal alpha-glucosidase, and peptidyl-prolyl cis- trans isomerase A, and lower expression of uromodulin and TALPID3, in urine may be associated with female SUI. PMID- 27193111 TI - Changes in hydration structure are necessary for collective motions of a multi domain protein. AB - Conformational motions of proteins are necessary for their functions. To date, experimental studies measuring conformational fluctuations of a whole protein structure have revealed that water molecules hydrating proteins are necessary to induce protein functional motions. However, the underlying microscopic mechanism behind such regulation remains unsolved. To clarify the mechanism, multi-domain proteins are good targets because it is obvious that water molecules between domains play an important role in domain motions. Here, we show how changes in hydration structure microscopically correlate with large-amplitude motions of a multi-domain protein, through molecular dynamics simulation supported by structural analyses and biochemical experiments. We first identified collective domain motions of the protein, which open/close an active-site cleft between domains. The analyses on changes in hydration structure revealed that changes in local hydration in the depth of the cleft are necessary for the domain motion and vice versa. In particular, 'wetting'/'drying' at a hydrophobic pocket and 'adsorption'/'dissociation' of a few water molecules at a hydrophilic crevice in the cleft were induced by dynamic rearrangements of hydrogen-bond networks, and worked as a switch for the domain motions. Our results microscopically demonstrated the importance of hydrogen-bond networks of water molecules in understanding energy landscapes of protein motions. PMID- 27193114 TI - The standardization of urodynamic reporting in the International Urogynecology Journal. PMID- 27193113 TI - Functional mapping of the pelvic floor and sphincter muscles from high-density surface EMG recordings. AB - INTRODUCTION AND HYPOTHESIS: Knowledge of the innervation of pelvic floor and sphincter muscles is of great importance to understanding the pathophysiology of female pelvic floor dysfunctions. This report presents our high-density intravaginal and intrarectal electromyography (EMG) probes and a comprehensive innervation zone (IZ) imaging technique based on high-density EMG readings to characterize the IZ distribution. METHODS: Both intravaginal and intrarectal probes are covered with a high-density surface electromyography electrode grid (8 * 8). Surface EMG signals were acquired in ten healthy women performing maximum voluntary contractions of their pelvic floor. EMG decomposition was performed to separate motor-unit action potentials (MUAPs) and then localize their IZs. RESULTS: High-density surface EMG signals were successfully acquired over the vaginal and rectal surfaces. The propagation patterns of muscle activity were clearly visualized for multiple muscle groups of the pelvic floor and anal sphincter. During each contraction, up to 218 and 456 repetitions of motor units were detected by the vaginal and rectal probes, respectively. MUAPs were separated with their IZs identified at various orientations and depths. CONCLUSIONS: The proposed probes are capable of providing a comprehensive mapping of IZs of the pelvic floor and sphincter muscles. They can be employed as diagnostic and preventative tools in clinical practices. PMID- 27193115 TI - Inference to the best explanation and mechanisms in medicine. AB - This article considers the prospects of inference to the best explanation (IBE) as a method of confirming causal claims vis-a-vis the medical evidence of mechanisms. I show that IBE is actually descriptive of how scientists reason when choosing among hypotheses, that it is amenable to the balance/weight distinction, a pivotal pair of concepts in the philosophy of evidence, and that it can do justice to interesting features of the interplay between mechanistic and population level assessments. PMID- 27193117 TI - Comment on "Linfotaping with kinesio(r) tape to manage and treat lymphedema patients: safety and tolerability are more important the efficacy?". PMID- 27193118 TI - Comparison of the FACT-C, EORTC QLQ-CR38, and QLQ-CR29 quality of life questionnaires for patients with colorectal cancer: a literature review. AB - PURPOSE: The purpose of this review was to compare the development, characteristics, validity, and reliability of three widely used quality of life (QOL) assessment tools used in colorectal cancer (CRC) patients: the Functional Assessment of Cancer Therapy-Colorectal (FACT-C), the European Organization for Research and Treatment of Cancer Quality of Life (EORTC) Quality of Life Questionnaire Colorectal Cancer Module (QLQ-CR38) and its successor, the QLQ CR29. METHODS: A literature search was conducted using Ovid EMBASE and EMBASE Classic (1996-2015 Week 39), Ovid MEDLINE and OLDMEDLINE (1996 September Week 4 2015), and the Cochrane Central Register of Controlled Trials (up to August 2015) to identify studies that discussed the FACT-C, EORTC QLQ-CR38, and QLQ-CR29 including, but not limited to, their development, characteristics, validity, and reliability. RESULTS: The FACT-C consists of 36 items, presented on a 5-point Likert scale, in four domains of well-being (physical, emotional, social, and functional), and the Colorectal Cancer Subscale (CCS). The physical and social well-being scales showed reasonable internal consistency (Cronbach's alpha coefficient > 60) in all studied populations. The EORTC QLQ-CR38 (38 items) and the QLQ-CR29 (29 items) are implemented in conjunction with the core QLQ-C30 (30 items); all are presented in 4-point Likert scales. Seven scales in the QLQ-CR38 demonstrated good internal consistency (Cronbach's alpha coefficient > 0.70). In the QLQ-CR29, three scales had a Cronbach's alpha coefficient of less than 0.70. CONCLUSION: The FACT-C, QLQ-CR38, and QLQ-CR29 have been extensively validated. However, analysis of their characteristics, validity, and reliability suggest differing suitability in assessing QOL in specific clinical situations. PMID- 27193116 TI - The relationship between mindfulness, pain intensity, pain catastrophizing, depression, and quality of life among cancer survivors living with chronic neuropathic pain. AB - PURPOSE: This study aims to examine if mindfulness is associated with pain catastrophizing, depression, disability, and health-related quality of life (HRQOL) in cancer survivors with chronic neuropathic pain (CNP). METHOD: We conducted a cross-sectional survey with cancer survivors experiencing CNP. Participants (n = 76) were men (24 %) and women (76 %) with an average age of 56.5 years (SD = 9.4). Participants were at least 1 year post-treatment, with no evidence of cancer, and with symptoms of neuropathic pain for more than three months. Participants completed the Five Facets Mindfulness Questionnaire (FFMQ), along with measures of pain intensity, pain catastrophizing, pain interference, depression, and HRQOL. RESULTS: Mindfulness was negatively correlated with pain intensity, pain catastrophizing, pain interference, and depression, and it was positively correlated with mental health-related HRQOL. Regression analyses demonstrated that mindfulness was a negative predictor of pain intensity and depression and a positive predictor of mental HRQOL after controlling for pain catastrophizing, age, and gender. The two mindfulness facets that were most consistently associated with better outcomes were non-judging and acting with awareness. Mindfulness significantly moderated the relationships between pain intensity and pain catastrophizing and between pain intensity and pain interference. CONCLUSION: It appears that mindfulness mitigates the impact of pain experiences in cancer survivors experiencing CNP post-treatment. IMPLICATIONS FOR CANCER SURVIVORS: This study suggests that mindfulness is associated with better adjustment to CNP. This provides the foundation to explore whether mindfulness-based interventions improve quality of life among cancer survivors living with CNP. PMID- 27193119 TI - Capacity of the Edmonton Symptom Assessment System and the Canadian Problem Checklist to screen clinical insomnia in cancer patients. AB - PURPOSE: Insomnia is highly prevalent in cancer patients. Efficacious treatments exist for this condition but, for these interventions to be offered, an effective screening needs to be carried out beforehand. The pan-Canadian practice guidelines on sleep disturbances provide recommendations on how to use the Edmonton Symptom Assessment System (ESAS) and the Canadian Problem Checklist (CPC) to screen for sleep difficulties in cancer. However, empirical evidence to support these recommendations is lacking. The goal of this study was to assess the capacity of the ESAS (drowsiness and "other" items) and the CPC (sleep item) to screen for clinical insomnia in cancer patients. METHODS: As part of routine care, 615 patients with various cancer types completed the ESAS, the CPC, and the Insomnia Severity Index, used as the standard for establishing the presence of clinical insomnia. RESULTS: None of the criteria provided an effective screening when used alone. No patient used the ESAS-other item to report sleep difficulties. The sensitivity and specificity rates of the CPC-sleep item alone were 60.4 and 89.6 %, respectively. A score >=2 on the ESAS-drowsiness item had a sensitivity of 61.5 % and a specificity of 75.4 %. When used in combination, the best option was scoring positively on the CPC-sleep item OR a score >=2 on the ESAS-drowsiness item (sensitivity 84.2 %; specificity 69.7 %). CONCLUSIONS: When used alone, the CPC-sleep and the ESAS-drowsiness items yielded insufficient sensitivity rates for a first screening, but when used in combination, they provided a good balance between sensitivity and specificity. PMID- 27193120 TI - Synthesis and characterization of shape-memory poly carbonate urethane microspheres for future vascular embolization. AB - Two types of shape memory poly carbonate urethanes (PCUs) microspheres were synthesized by pre-polymerization and suspension polymerization, based on Polycarbonate diol (PCDL) as the soft segment, Isophorone diisocyanate (IPDI) and 1,6-hexamethylene diisocyanate (HDI) as the hard segments and 1,4-butanediol (BDO) as the chain expanding agent. The structure, crystallinity, and thermal property of the two synthesized PCUs were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Differential scanning calorimetery (DSC), respectively. The results showed that the two types of PCUs exhibited high thermal stability with phase separation and semi-crystallinity. Also, the results of the compression test displayed that the shape fixity and the shape recovery of two PCUs were more than 90% compared to the originals, indicating their similar bio-applicability and shape-memory properties. The tensile strength, elongation at break was enhanced by introducing and increasing content of HDI. The water contact angles of PCUs decreased and their surface tension increased by surface modified with Bovine serum albumin (BSA). Furthermore, the biological study results of two types of PCUs from the platelet adhesion test and the cell proliferation inhibition test indicated they had some biocompatibilites. Hence, the PCU microspheres might represent a smart and shape memory embolic agent for vascular embolization. PMID- 27193122 TI - An unusual case of ocular tuberculosis presenting as subretinal abscess with posterior scleritis. AB - We report an unusual presentation of ocular tuberculosis with subretinal abscess with associated posterior scleritis. This is a first-of-its-kind report of such an association. A 26-year-old female presented to us with complaints of redness, pain, and decreased vision in her left eye since 1 week. On examination, the vision in her right eye was 6/6 and in the left eye was 1/60. Detailed ocular evaluation revealed exudative retinal detachment, subretinal abscess, and disk edema. Ocular and systemic investigations were consistent with presumed tubercular etiology and posterior scleritis. The patient was treated with a course of anti-tubercular therapy, under cover of oral steroids. The vision improved in subsequent visits and at the last follow-up 6 months later, the lesion had resolved completely with a best-corrected visual acuity of 20/40. PMID- 27193121 TI - The leguminous lectin of Lonchocarpus araripensis promotes antinociception via mechanisms that include neuronal inhibition of Na(+) currents. AB - OBJECTIVE AND DESIGN: Sodium channels are highly expressed in nociceptive sensory neurons during hypernociceptive conditions. Based on the presence of a glycosidic portion in the sodium channel beta subunit associated to the antinociceptive effect of leguminous lectins via lectin domain, this study investigated the antinociceptive activity of the lectin isolated from Lonchocarpus araripensis seeds (LAL) in mice behavioral models and in NaV current in the nociceptor of rat dorsal root ganglion (DRG). MATERIAL/METHODS: LAL antinociceptive activity and the participation of opioid system, lectin domain and sodium channels were evaluated in Swiss mice models of nociception (formalin, capsaicin, hot plate, tail flick, von Frey) and in primary cultures of Wistar rats neurons of DRG (patch clamp). RESULTS: LAL presented inhibitory effects in the nociception induced by chemical and mechanical, but not by thermal stimuli and reduced total Na(+) current. LAL activity was inhibited by the lectin association with its binding sugar N-acethyl-glucosamine. CONCLUSION: LAL inhibits peripheral hypernociception by mechanisms that involve the lectin domain, inflammatory mediators and Na(+) channels. The innovative inhibitory action of leguminous lectins on NaV current brings new insights for the investigation of sodium channels role in nociception. PMID- 27193123 TI - Reduced ocular surface disease index (OSDI) scores in patients with isotretinoin treatment. AB - To evaluate the changes in ocular surface and functions of tear-film in patients treated with systemic isotretinoin, to assess diagnostic performance of ocular surface disease index (OSDI) test in the dry eye conditions in association with the use of isotretinoin, and to determine the correlation between all tear-film function tests, OSDI and the dose and duration of isotretinoin administration. One hundred and twenty eyes of 60 subjects treated with oral isotretinoin were enrolled. All patients underwent ophthalmic examination at the baseline and another examination during the course of treatment. Biomicroscopic ophthalmic examination of the meibomian glands, non-anesthetized Schirmer test, and tear film break-up time (BUT) were performed. Subjective ocular complaints were scored with an OSDI questionnaire. Average Schirmer scores were not significantly changed by isotretinoin treatment. There were significant differences in the average OSDI score, the average meibomian gland disease (MGD) grade and average BUT value of both eyes during the treatment compared with baseline values (p < 0.01). There was a statistically significant inverse correlation between MGD grade and BUT value. There was no significant correlation between BUT value, OSDI score, Schirmer score, MGD grade, the total and divided dose of isotretinoin and the duration of treatment. The follow-up time was 4.01 +/- 1.3 months (range 1.5 6 months). Systemic isotretinoin treatment can cause alterations in the tear film and dry eye symptoms. The OSDI test can be used as a diagnostic test for patients receiving systemic isotretinoin treatment. PMID- 27193125 TI - Type specific persistence of high risk human papillomavirus (HPV) as indicator of high grade cervical squamous intraepithelial lesions in young women: population based prospective follow up study. PMID- 27193126 TI - Slow induction of brain death leads to decreased renal function and increased hepatic apoptosis in rats. AB - BACKGROUND: Donor brain death (BD) is an independent risk factor for graft survival in recipients. While in some patients BD results from a fast increase in intracranial pressure, usually associated with trauma, in others, intracranial pressure increases more slowly. The speed of intracranial pressure increase may be a possible risk factor for renal and hepatic graft dysfunction. This study aims to assess the effect of speed of BD induction on renal and hepatic injury markers. METHODS: BD induction was performed in 64 mechanically ventilated male Fisher rats by inflating a 4.0F Fogarty catheter in the epidural space. Rats were observed for 0.5, 1, 2 or 4 h following BD induction. Slow induction was achieved by inflating the balloon-catheter at a speed of 0.015 ml/min until confirmation of BD. Fast induction was achieved by inflating the balloon at 0.45 ml/min for 1 min. Plasma, kidney and liver tissue were collected for analysis. RESULTS: Slow BD induction led to higher plasma creatinine at all time points compared to fast induction. Furthermore, slow induction led to increased renal mRNA expression of IL-6, and renal MDA values after 4 h of BD compared to fast induction. Hepatic mRNA expression of TNF-alpha, Bax/Bcl-2, and protein expression of caspase-3 was significantly higher due to slow induction after 4 h of BD compared to fast induction. PMN infiltration was not different between fast and slow induction in both renal and hepatic tissue. CONCLUSION: Slow induction of BD leads to poorer renal function compared to fast induction. Renal inflammatory and oxidative stress markers were increased. Liver function was not affected by speed of BD induction but hepatic inflammatory and apoptosis markers increased significantly due to slow induction compared to fast induction. These results provide initial proof that speed of BD induction influences detrimental renal and hepatic processes which could signify different donor management strategies for patients progressing to BD at different speeds. PMID- 27193127 TI - Endoscopic Aspiration of a Cystic Midbrain Tumour through the 4th Ventricle. PMID- 27193124 TI - V-akt murine thymoma viral oncogene homolog 3 (AKT3) contributes to poor disease outcome in humans and mice with pneumococcal meningitis. AB - Pneumococcal meningitis is the most common and severe form of bacterial meningitis. Fatality rates are substantial, and long-term sequelae develop in about half of survivors. Here, we have performed a prospective nationwide genetic association study using the Human Exome BeadChip and identified gene variants in encoding dynactin 4 (DCTN4), retinoic acid early transcript 1E (RAET1E), and V akt murine thymoma viral oncogene homolog 3 (AKT3) to be associated with unfavourable outcome in patients with pneumococcal meningitis. No clinical replication cohort is available, so we validated the role of one of these targets, AKT3, in a pneumococcal meningitis mouse model. Akt3 deficient mice had worse survival and increased histopathology scores for parenchymal damage (infiltration) and vascular infiltration (large meningeal artery inflammation) but similar bacterial loads, cytokine responses, compared to wild-type mice. We found no differences in cerebrospinal fluid cytokine levels between patients with risk or non-risk alleles. Patients with the risk genotype (rs10157763, AA) presented with low scores on the Glasgow Coma Scale and high rate of epileptic seizures. Thus, our results show that AKT3 influences outcome of pneumococcal meningitis. PMID- 27193129 TI - Symptomatic capillary telangiectasia of the pons: three pediatric cases diagnosed by suspectibility-weighted imaging. AB - INTRODUCTION: Brain capillary telangiectasias (BCT) are small, clinically benign, usually asymptomatic and rarely seen lesions during childhood. Large symptomatic BCT during childhood are extremely rare, with only a few reports in the literature. They usually cannot be detected easily on conventional magnetic resonance imaging and angiography. METHODS: We present the first pediatric case series of large pontine BCT presenting with distinct symptoms and in whom the lesions were detected by susceptibility-weighted imaging (SWI), for the first time to date. SWI provides a crucial imaging modality for BCT. RESULTS: We suggest that the combination of signal intensity loss on SWI and focal enhancement in a lesion otherwise not seen on conventional MR images is diagnostic for BCT and serves to discard serious differential diagnoses with high specificity, reassuring patients and referring physicians. CONCLUSION: We would like to emphasize clinical and radiological findings of BCT and utility of SWI images on MRI for the confirmation of diagnosis in the pediatric age group. PMID- 27193128 TI - Scope of practice and outcomes of cerebrovascular procedures in children. AB - PURPOSE: The impact of scope of practice of providers (predominantly adult versus predominantly pediatric) on the outcomes of cerebrovascular procedures in children remains an issue of debate. We investigated the association of scope of practice with the outcomes of cerebrovascular interventions. METHODS: We performed a cohort study of all pediatric patients (younger than 18 years old) who underwent cerebrovascular procedures from 2009 to 2013 and were registered in the Statewide Planning and Research Cooperative System (SPARCS) database. In order to control for confounding, we used propensity score conditioning and mixed effects analysis to account for clustering at the hospital level. RESULTS: During the study period, there were 1243 pediatric patients who underwent cerebrovascular procedures and met the inclusion criteria. Of these, 631 (50.7 %) underwent treatment by providers with predominantly adult practices and 612 (49.3 %) by physicians who operated predominantly on children. The mixed-effects multivariable regression analysis demonstrated lack of association of predominantly adult practice with inpatient mortality (OR, 1.20; 95 % CI, 0.61 2.38), discharge to a facility (OR, 1.50; 95 % CI, 0.73-3.09), and length of stay (LOS) (adjusted difference, 0.003; 95 % CI, -0.09 to 0.10). These associations persisted in propensity-adjusted models. CONCLUSIONS: In a cohort of pediatric patients undergoing cerebrovascular procedures from a comprehensive all-payer database, we did not demonstrate a difference in mortality, discharge to a facility, and LOS between providers with predominantly adult and predominantly pediatric practices. PMID- 27193130 TI - Clinical and pathologic features of patients with non-epithelial ovarian cancer: retrospective analysis of a single institution 15-year experience. AB - PURPOSE: Non-epithelial ovarian cancers (NEOCs) are rare diseases. Despite their overall good prognosis, the best management and current prognostic factors remain unclear. The objective of our study was to assess the clinical and pathological features of NEOC patients treated in our institution in the last 15 years and to explore risk factors for relapse and survival. METHODS/PATIENTS: All patients with a pathological diagnosis of NEOC referred to the medical oncology department at Hospital Universitario Virgen del Rocio between 1999 and 2014 were included. Demographics, tumor characteristics, treatment procedures, and clinical follow-up were retrospectively collected. Risk factors for disease-free survival (DFS) and overall survival (OS) were assessed. RESULTS: Fifty-seven patients were included, 33 (58 %) had a sex cord-stromal tumor (SCST) and 24 (42 %) had a germ-cell tumor (GCT). Median age, non-conservative surgery rates and DFS were lower in the GCT cohort; however, salvage chemotherapy led to a high proportion of complete responses in this group translating into a 90 % 3-year OS rate in both NEOC subtypes. The only identified risk factors statistically significant were stage and tumour relapse that associated, respectively, with DFS (HR = 8.84; 95 % CI 1.85-42) and OS (HR = 11.02; 95 % CI 1.76-68.7). CONCLUSIONS: Despite their rarity, NEOCs remain a highly curable group of neoplasm. In our series, a more conservative treatment approach in ovarian GCTs revealed comparable OS outcomes to SCST. No new risk factors that would help in patient stratification were identified. PMID- 27193132 TI - Catching a Deceiver in the Act: Processes Underlying Deception in an Interactive Interview Setting. AB - Lying is known to evoke stress and cognitive load. Both form cues to deception and lead to an increase in sympathetic nervous system (SNS) activity. But in reality, deceivers stick to the truth most the time and only lie occasionally. The present study therefore examined in an interactive suspect interview setting, whether deceivers still have clearly diverging cognitive and emotional processes from truth tellers when only having the intention to lie incidentally. We found that deceivers who lied constantly diverge from truth tellers in SNS activity, self-reported cognitive load and stress. Across all interviews, SNS activity correlated stronger with self-reports of cognitive load than stress, which supports the cognitive load approach. Furthermore, deceivers who told the truth and lied on only one crucial question, particularly diverged in self-reported stress from truth-tellers. In terms of SNS activity and self-reported cognitive load, no differences were found. Theoretical and practical implications are discussed. PMID- 27193131 TI - Extracorporeal carbon dioxide removal (ECCO2R) in respiratory deficiency and current investigations on its improvement: a review. AB - The implementation of extracorporeal carbon dioxide removal (ECCO2R) as one of the extracorporeal life support system is getting more attention today. Thus, the objectives of this paper are to study the clinical practice of commercial ECCO2R system, current trend of its development and also the perspective on future improvement that can be done to the existing ECCO2R system. The strength of this article lies in its review scope, which focuses on the commercial ECCO2R therapy in the market based on membrane lung and current investigation to improve the efficiency of the ECCO2R system, in terms of surface modification by carbonic anhydrase (CA) immobilization technique and respiratory electrodialysis (R-ED). Our methodology approach involves the identification of relevant published literature from PubMed and Web of Sciences search engine using the terms Extracorporeal Carbon Dioxide Removal (ECCO2R), Extracorporeal life support, by combining terms between ECCO2R and CA and also ECCO2R with R-ED. This identification only limits articles in English language. Overall, several commercial ECCO2R systems are known and proven safe to be used in patients in terms of efficiency, safety and risk of complication. In addition, CA-modified hollow fiber for membrane lung and R-ED are proven to have good potential to be applied in conventional ECCO2R design. The detailed technique and current progress on CA immobilization and R-ED development were also reviewed in this article. PMID- 27193133 TI - Evidence for potential involvement of pro-inflammatory adipokines in the pathogenesis of idiopathic intracranial hypertension. AB - Background Although specific role players are currently unknown, contribution of inflammatory mediators has been suggested in the pathophysiology of idiopathic intracranial hypertension (IIH), which is a disease more prevalent in obese female individuals of childbearing age. We aimed to investigate the levels of adipokines and cytokines to demonstrate possible markers for inflammation that participate in IIH pathophysiology and their association with clinical features of IIH. Methods IIH patients, diagnosed according to the revised criteria, and age-, gender- and body mass index (BMI)-matched healthy controls were enrolled in this study. Serum samples were evaluated for insulin-like growth factor 1, insulin, nesfatin, adiponectin, interleukin (IL)-1beta, IL-6, IL-8, leptin, plasminogen activator inhibitor type-1, resistin, tumour necrosis factor-alpha (TNF-alpha) and monocyte chemotactic protein 1 via enzyme-linked immunosorbent assay or multiplex immunoassays. Results IL-1beta level was significantly higher ( p = 0.012), and IL-8 and TNF-alpha levels were significantly lower in the IIH group ( p < 0.001 and p = 0.008, respectively) compared to the control group. There were no correlations between the cytokine/adipokine levels and age, BMI, disease duration, and cerebrospinal fluid oligoclonal bands. There were also no significant differences in cytokine and adipokine levels between IIH patients regarding visual impairment. However, statistically significant differences were found between IIH patients with relapse versus healthy controls regarding IL 1beta ( p = 0.007), IL-8 ( p = 0.001) and TNF-alpha ( p = 0.017) levels. Other investigated cytokines and adipokines showed no significant alterations in IIH patients investigated in the remission period. Conclusion Altered serum levels of IL-1beta, IL-8 and TNF-alpha seem to be associated with IIH pathogenesis, and these cytokines may be used as prognostic markers in IIH to predict relapse. PMID- 27193134 TI - Platelet Activating Factor (PAF) Receptor Deletion or Antagonism Attenuates Severe HSV-1 Meningoencephalitis. AB - Herpes simplex virus type 1 (HSV-1) is a human pathogen that may cause severe encephalitis. The exacerbated immune response against the virus contributes to the disease severity and death. Platelet activating factor (PAF) is a mediator capable of inducing increase in vascular permeability, production of cytokines on endothelial cells and leukocytes. We aimed to investigate the activation of PAF receptor (PAFR) and its contribution to the severity of the inflammatory response in the brain following HSV-1 infection. C57BL/6 wild-type (WT) and PAFR deficient (PAFR-/-) mice were inoculated intracranially with 104 plaque-forming units (PFU) of HSV-1. Visualization of leukocyte recruitment was performed using intravital microscopy. Cells infiltration in the brain tissue were analyzed by flow cytometry. Brain was removed for chemokine assessment by ELISA and for histopathological analysis. The pharmacological inhibition by the PAFR antagonist UK-74,505 was also analyzed. In PAFR-/- mice, there was delayed lethality but no difference in viral load. Histopathological analysis of infected PAFR-/- mice showed that brain lesions were less severe when compared to their WT counterparts. Moreover, PAFR-/- mice showed less TCD4+, TCD8+ and macrophages in brain tissue. This reduction of the presence of leukocytes in parenchyma may be mechanistically explained by a decrease in leukocytes rolling and adhesion. PAFR /- mice also presented a reduction of the chemokine CXCL9 in the brain. In addition, by antagonizing PAFR, survival of C57BL/6 infected mice increased. Altogether, our data suggest that PAFR plays a role in the pathogenesis of experimental HSV-1 meningoencephalitis, and its blockade prevents severe disease manifestation. PMID- 27193136 TI - An evidence-based resource for the management of comorbidities associated with childhood overweight and obesity. AB - PURPOSE: Overweight and obesity in children and adolescents is often accompanied by obesity-related comorbidities. An integrative review of the literature was performed to create a comprehensive algorithm to help primary care providers manage the common comorbidities associated with childhood overweight and obesity. DATA SOURCES: The Cumulative Index to Nursing and Allied Health Literature, ProQuest Nursing and Allied Health Source, and PubMed databases were searched. Evidence from 2002 to present was reviewed. Guidelines and algorithms from the American Academy of Pediatrics, National Association of Pediatric Nurse Practitioners, American Heart Association, American Diabetes Association, Centers for Disease Control and Prevention, National Heart, Lung, and Blood Institute, Agency for Healthcare and Research Quality, U.S. Department of Health and Human Services, and the International Diabetes Federation were also reviewed. CONCLUSIONS: Key information was extracted and data sources ranked according to the Polit and Beck evidence hierarchy. Highest level evidence guided the selection and development of recommendations to formulate a comprehensive resource for the recognition and management of pediatric hypertension, sleep apnea, vitamin D deficiency, nonalcoholic fatty liver disease, dyslipidemia, thyroid disease, diabetes mellitus, insulin resistance, metabolic syndrome, and polycystic ovarian syndrome. IMPLICATIONS FOR PRACTICE: The Childhood Overweight and Obesity Comorbidities Resource provides a consistent, convenient point-of care reference to help primary care providers improve pediatric health outcomes. PMID- 27193135 TI - Effectiveness of non invasive external pelvic compression: a systematic review of the literature. AB - INTRODUCTION: Pelvic fractures might carry a significant risk of bleeding. A wide variety of pelvic binders together with pelvic sheets are available and offer an adjunct to the initial management of poly-trauma patients with pelvic injuries. These devices are collectively referred to as pelvic circumferential compression devices (PCCDs). The aim of this study was to review the literature for evidence pertinent to the efficacy and safety of PCCDs. METHODS: Using the PRISMA guidelines a systematic search on PubMed, Web of Science, CINAHL, Embase and Scopus was carried out. Articles included were in English language and published between 1999 and 2015. Studies included were appraised with narrative data synthesis. RESULTS: Seven articles addressed mechanical properties of non invasive external mechanical devices, six articles focused on physiological aspects, and three studies evaluated the pressure characteristics of these devices. We found 4 case reports regarding adverse effects. None of the studies identified addressed the cost effectiveness or pain relief issues related to the use of PCCDs. CONCLUSIONS: Based on available literature, PCCDs are widely used in the initial management of patients with suspected pelvic bleeding. There is evidence to suggest that external compression reduces disrupted pelvic rings. There are some complications reported following application of PCCDs. Hemorrhagic source and physiological effectiveness of PCCDs needs to be addressed in future studies. In the meantime judicious application of PCCDs will continue to be recommended. PMID- 27193137 TI - The influence of the commensal and pathogenic gut microbiota on prion disease pathogenesis. AB - Prion diseases are a unique group of transmissible, chronic, neurodegenerative disorders. Following peripheral exposure (e.g. oral), prions often accumulate first within the secondary lymphoid tissues before they infect the central nervous system (CNS). Prion replication within secondary lymphoid tissues is crucial for the efficient spread of disease to the CNS. Once within the CNS, the responses of innate immune cells within it can have a significant influence on neurodegeneration and disease progression. Recently, there have been substantial advances in our understanding of how cross-talk between the host and the vast community of commensal microorganisms present at barrier surfaces such as the gut influences the development and regulation of the host's immune system. These effects are evident not only in the mucosal immune system in the gut, but also in the CNS. The actions of this microbial community (the microbiota) have many important beneficial effects on host health, from metabolism of nutrients and regulation of host development to protection from pathogen infection. However, the microbiota can also have detrimental effects in some circumstances. In this review we discuss the many and varied interactions between prions, the host and the gut microbiota. Particular emphasis is given to the ways by which changes to the composition of the commensal gut microbiota or congruent pathogen infection may influence prion disease pathogenesis and/or disease susceptibility. Understanding how these factors influence prion pathogenesis and disease susceptibility is important for assessing the risk to infection and the design of novel opportunities for therapeutic intervention. PMID- 27193138 TI - Immunopathology of lung diseases: introduction for the special issue. PMID- 27193140 TI - [Not Available]. PMID- 27193139 TI - Low temperature caused modifications in the arrangement of cell wall pectins due to changes of osmotic potential of cells of maize leaves (Zea mays L.). AB - The cell wall emerged as one of the important structures in plant stress responses. To investigate the effect of cold on the cell wall properties, the content and localization of pectins and pectin methylesterase (PME) activity, were studied in two maize inbred lines characterized by different sensitivity to cold. Low temperature (14/12 degrees C) caused a reduction of pectin content and PME activity in leaves of chilling-sensitive maize line, especially after prolonged treatment (28 h and 7 days). Furthermore, immunocytohistological studies, using JIM5 and JIM7 antibodies, revealed a decrease of labeling of both low- and high-methylesterified pectins in this maize line. The osmotic potential, quantified by means of incipient plasmolysis was lower in several types of cells of chilling-sensitive maize line which was correlated with the accumulation of sucrose. These studies present new finding on the effect of cold stress on the cell wall properties in conjunction with changes in the osmotic potential of maize leaf cells. PMID- 27193141 TI - Decoupling optical function and geometrical form using conformal flexible dielectric metasurfaces. AB - Physical geometry and optical properties of objects are correlated: cylinders focus light to a line, spheres to a point and arbitrarily shaped objects introduce optical aberrations. Multi-functional components with decoupled geometrical form and optical function are needed when specific optical functionalities must be provided while the shapes are dictated by other considerations like ergonomics, aerodynamics or aesthetics. Here we demonstrate an approach for decoupling optical properties of objects from their physical shape using thin and flexible dielectric metasurfaces which conform to objects' surface and change their optical properties. The conformal metasurfaces are composed of silicon nano-posts embedded in a polymer substrate that locally modify near-infrared (lambda=915 nm) optical wavefronts. As proof of concept, we show that cylindrical lenses covered with metasurfaces can be transformed to function as aspherical lenses focusing light to a point. The conformal metasurface concept is highly versatile for developing arbitrarily shaped multi functional optical devices. PMID- 27193145 TI - Corrigendum. AB - Nikopensius T, Saag M, Jagomagi T, Annilo T, Kals M, Kivistik PA, Milani L, Metspalu A. 2013. A missense mutation in DUSP6 is associated with Class III malocclusion. J Dent Res. 92(10):893-898. (Original DOI: 10.1177/0022034513502790). PMID- 27193144 TI - Oncological outcomes of patients with incidental pathological T3a stage small renal cell carcinoma after partial nephrectomy. AB - PURPOSE: This study was designed to evaluate and compare the oncological outcomes of patients with pathological T1a (pT1a) small renal cell carcinomas (RCCs) with those with incidental pathological T3a (pT3a) RCCs who have been treated using partial nephrectomy (PN). METHODS: We retrospectively evaluated the records of 1367 consecutive patients who underwent PN for small RCCs (<=4 cm) between 1997 and 2014. The curves for recurrence-free, cancer-specific, and overall survival were estimated using the Kaplan-Meier method. Cox regression analysis was used to estimate the prognostic significance of each variable. RESULTS: Of the 1367 small RCC patients identified, 1324 (96.8 %) had pT1a lesions and 43 (3.2 %) had pT3a lesions. The median ages of the pT1a and pT3a patients were 53.9 and 58.1 years, respectively. Patients received follow-up for a median of 54 months. The 5- and 10-year RFS rates in patients with pT1a and pT3a RCCs were 98.0 and 95.2 %, and 94.4 and 95.2 %, respectively (P = 0.521). None of the patients with recurrent tumors in the pT3a group have died by the time of the writing of this report. A multivariate Cox proportional hazards model showed that tumor size was a significant predictor of RFS and CSS (P < 0.05). However, pT stage (pT3a vs. pT1a) was not a significant predictor of RFS, CSS, or OS (P = 0.104, P = 0.573, and P = 0.441, respectively). CONCLUSIONS: Our study found that pT3a stage disease following PN for small RCCs (<=4 cm) had similar oncological outcomes to those of pT1a stage. PMID- 27193142 TI - Diverse mechanisms shape the evolution of virulence factors in the potato late blight pathogen Phytophthora infestans sampled from China. AB - Evolution of virulence in plant pathogens is still poorly understood but the knowledge is important for the effective use of plant resistance and sustainable disease management. Spatial population dynamics of virulence, race and SSR markers in 140 genotypes sampled from seven geographic locations in China were compared to infer the mechanisms driving the evolution of virulence in Phytophthora infestans (P. infestans). All virulence types and a full spectrum of race complexity, ranging from the race able to infect the universally susceptible cultivar only to all differentials, were detected. Eight and two virulence factors were under diversifying and constraining selection respectively while no natural selection was detected in one of the virulence types. Further analyses revealed excesses in simple and complex races but deficiency in intermediate race and negative associations of annual mean temperature at the site from which pathogen isolates were collected with frequency of virulence to differentials and race complexity in the pathogen populations. These results suggest that host selection may interact with other factors such as climatic conditions in determining the evolutionary trajectory of virulence and race structure in P. infestans and global warming may slow down the emergence of new virulence in the pathogen. PMID- 27193147 TI - CORR Insights(r): Which Sport Activity Levels Are Achieved in Patients After Resection and Endoprosthetic Reconstruction for a Proximal Femur Bone Sarcoma? PMID- 27193146 TI - First Cultivation of Health-Associated Tannerella sp. HOT-286 (BU063). AB - Despite significant advances in recent years in culture-independent molecular microbiology methods, the detailed study of individual bacterial species still relies on having pure cultures in the laboratory. Yet, more than a third of the approximately 700 bacterial taxa found in the human oral cavity are as yet uncultivated in vitro. One such taxon, Tannerella sp. HOT-286 (phylotype BU063), is the focus of much interest since it is associated with periodontal health, while Tannerella forsythia, its closest phylogenetic neighbor, is strongly associated with periodontal disease. HOT-286, however, has remained uncultivated despite the efforts of several research groups, spanning over a decade. The aim of this study was to cultivate Tannerella sp. HOT-286. A heavily diluted sample of subgingival plaque was inoculated onto culture plates supplemented with siderophores (pyoverdines-Fe complex or desferricoprogen) or a neat plaque suspension. After 8 d of anaerobic incubation, microcolonies and colonies showing satellitism were passaged onto fresh culture plates cross-streaked with potential helper strains or onto cellulose-acetate membranes placed over lawn cultures of helper strains. Subcultured colonies were identified by 16S rRNA gene sequencing, and purity was confirmed by sequencing 20 clones per library prepared from a single colony. Three colonies of interest (derived from pyoverdines- and plaque supplemented plates) were identified as Tannerella sp. HOT-286. The isolates were found to be incapable of independent growth, requiring helpers such as Propionibacterium acnes and Prevotella intermedia for stimulation, with best growth on membranes over "helper" lawns. A representative isolate was subjected to phenotypic characterization and found to produce a range of glycosidic and proteolytic enzymes. Further comparison of this novel "periodontal health associated" taxon with T. forsythia will be valuable in investigating virulence factors of the latter and possible health benefits of the former. PMID- 27193148 TI - Safer Operations, But Worse Surgeons? PMID- 27193149 TI - CORR Insights((r)): Modular to Monoblock: Difficulties of Detaching the M(2)a Magnum(TM) Head Are Common in Metal-on-metal Revisions. PMID- 27193150 TI - CORR Insights(r): Length of Endoprosthetic Reconstruction in Revision Knee Arthroplasty Is Associated With Complications and Reoperations. PMID- 27193151 TI - Human aqueous humor proteome in cataract, glaucoma, and pseudoexfoliation syndrome. AB - Twenty-nine human aqueous humor samples from patients with eye diseases such as cataract and glaucoma with and without pseudoexfoliation syndrome were characterized by LC-high resolution MS analysis. In total, 269 protein groups were identified with 1% false discovery rate including 32 groups that were not reported previously for this biological fluid. Since the samples were analyzed individually, but not pooled, 36 proteins were identified in all samples, comprising the constitutive proteome of the fluid. The most dominant molecular function of aqueous humor proteins as determined by GO analysis is endopeptidase inhibitor activity. Label-free protein quantification showed no significant difference between glaucoma and cataract aqueous humor proteomes. At the same time, we found decrease in the level of apolipoprotein D as a marker of the pseudoexfoliation syndrome. The data are available from ProteomeXchange repository (PXD002623). PMID- 27193152 TI - Mechanical roles of apical constriction, cell elongation, and cell migration during neural tube formation in Xenopus. AB - Neural tube closure is an important and necessary process during the development of the central nervous system. The formation of the neural tube structure from a flat sheet of neural epithelium requires several cell morphogenetic events and tissue dynamics to account for the mechanics of tissue deformation. Cell elongation changes cuboidal cells into columnar cells, and apical constriction then causes them to adopt apically narrow, wedge-like shapes. In addition, the neural plate in Xenopus is stratified, and the non-neural cells in the deep layer (deep cells) pull the overlying superficial cells, eventually bringing the two layers of cells to the midline. Thus, neural tube closure appears to be a complex event in which these three physical events are considered to play key mechanical roles. To test whether these three physical events are mechanically sufficient to drive neural tube formation, we employed a three-dimensional vertex model and used it to simulate the process of neural tube closure. The results suggest that apical constriction cued the bending of the neural plate by pursing the circumference of the apical surface of the neural cells. Neural cell elongation in concert with apical constriction further narrowed the apical surface of the cells and drove the rapid folding of the neural plate, but was insufficient for complete neural tube closure. Migration of the deep cells provided the additional tissue deformation necessary for closure. To validate the model, apical constriction and cell elongation were inhibited in Xenopus laevis embryos. The resulting cell and tissue shapes resembled the corresponding simulation results. PMID- 27193155 TI - Higher Serum Bisphenol A Levels in Diabetic Hemodialysis Patients. AB - BACKGROUND: Bisphenol A (BPA) has been implicated as an 'endocrine disruptor'. We aimed at exploring the association between serum BPA levels and patient characteristics, particularly the presence of diabetes mellitus, and laboratory parameters in hemodialysis patients. METHODS: This study included 47 chronic hemodialysis patients. Patient characteristics were recorded. Blood was drawn before and after hemodialysis session. Serum BPA levels were measured by the high performance-liquid-chromatography and laboratory parameters were measured by using standard methods. RESULTS: In hemodialysis patients, postdialysis serum BPA levels were significantly higher than predialysis after a single hemodialysis session (5.57 +/- 1.2 vs. 4.06 +/- 0.73, p < 0.0001). Predialysis serum BPA levels were significantly higher in patients with diabetes than non-diabetics (4.4 +/- 0.6 vs. 3.9 +/- 0.7, p = 0.025). No association was found between serum BPA levels and patient characteristics, and particularly laboratory parameters. CONCLUSION: Serum BPA levels were rising significantly after a single dialysis session. Diabetic hemodialysis patients had higher predialysis serum BPA levels. PMID- 27193154 TI - High Nutrient Concentration Can Induce Virulence Factor Expression and Cause Higher Virulence in an Environmentally Transmitted Pathogen. AB - Environmentally transmitted opportunistic pathogens shuttle between two substantially different environments: outside-host and within-host habitats. These environments differ from each other especially with respect to nutrient availability. Consequently, the pathogens are required to regulate their behavior in response to environmental cues in order to survive, but how nutrients control the virulence in opportunistic pathogens is still poorly understood. In this study, we examined how nutrient level in the outside-host environment affects the gene expression of putative virulence factors of the opportunistic fish pathogen Flavobacterium columnare. The impact of environmental nutrient concentration on bacterial virulence was explored by cultivating the bacteria in various nutrient conditions, measuring the gene expression of putative virulence factors with RT qPCR and, finally, experimentally challenging rainbow trout (Oncorhynchus mykiss) fry with these bacteria. Our results show that increased environmental nutrient concentration can increase the expression of putative virulence genes, chondroitinase (cslA) and collagenase, in the outside-host environment and may lead to more rapid fish mortality. These findings address that the environmental nutrients may act as significant triggers of virulence gene expression and therefore contribute to the interaction between an environmentally transmitted opportunistic pathogen and its host. PMID- 27193153 TI - A lumped stiffness model of intermuscular and extramuscular myofascial pathways of force transmission. AB - Mechanical behavior of skeletal muscles is commonly modeled under the assumption of mechanical independence between individual muscles within a muscle group. Epimuscular myofascial force transmission via the connective tissue network surrounding a muscle challenges this assumption as it alters the force distributed to the tendons of individual muscles. This study aimed to derive a lumped estimate of stiffness of the intermuscular and extramuscular connective tissues and to assess changes in such stiffness in response to a manipulation of the interface between adjacent muscles. Based on in situ measurements of force transmission in the rat plantar flexors, before and after resection of their connective tissue network, a nonlinear estimate of epimuscular myofascial stiffness was quantified and included in a multi-muscle model with lumped parameters which allows for force transmission depending on the relative position between the muscles in the group. Such stiffness estimate was assessed for a group with normal intermuscular connective tissues and for a group with increased connectivity, mimicking scar tissue development. The model was able to successfully predict the amount of epimuscular force transmission for different experimental conditions than those used to obtain the model parameters. The proposed nonlinear stiffness estimates of epimuscular pathways could be integrated in larger musculoskeletal models, to provide more accurate predictions of force when effects of mechanical interaction or altered epimuscular connections, e.g. after surgery or injury, are substantial. PMID- 27193156 TI - Clinical Pharmacokinetics and Pharmacodynamics of Ledipasvir/Sofosbuvir, a Fixed Dose Combination Tablet for the Treatment of Hepatitis C. AB - Ledipasvir/sofosbuvir (Harvoni(r)), a fixed-dose combination tablet of an NS5A inhibitor ledipasvir and an NS5B polymerase inhibitor sofosbuvir, is approved in the US, European Union, Canada, and other regions for the treatment of chronic hepatitis C virus infection in adults. Following absorption, ledipasvir reaches maximum plasma concentrations (T max) 4-4.5 h post-dose and is eliminated with a terminal half-life (t 1/2) of 47 h. Sofosbuvir undergoes intracellular activation to an active triphosphate GS-461203 (not detected in plasma) and ultimately to GS 331007, a predominant circulating metabolite, which is the primary analyte of interest in clinical pharmacology studies. Sofosbuvir is rapidly absorbed and eliminated from plasma (T max: 0.8-1 h; t 1/2: 0.5 h). The peak plasma concentrations for GS-331007 are achieved between 3.5 and 4 h post-dose; the elimination t 1/2 for GS-331007 is 27 h. Ledipasvir/sofosbuvir exhibits a favorable clinical pharmacology profile; it can be administered once daily without regard to food and does not require dose modification in hepatitis C virus-infected patients with any degree of hepatic impairment or mild to moderate renal impairment. The pharmacokinetic profiles of ledipasvir, sofosbuvir, and GS 331007 (predominant circulating metabolite of sofosbuvir) are not significantly affected by demographic variables; pharmacokinetic/pharmacodynamic analyses reveal no exposure-response relationships for efficacy or safety. The review summarizes the clinical pharmacokinetics, pharmacodynamics, and pharmacokinetic/pharmacodynamic analyses for ledipasvir/sofosbuvir. PMID- 27193157 TI - Presenting GECO: An eyetracking corpus of monolingual and bilingual sentence reading. AB - This article introduces GECO, the Ghent Eye-Tracking Corpus, a monolingual and bilingual corpus of the eyetracking data of participants reading a complete novel. English monolinguals and Dutch-English bilinguals read an entire novel, which was presented in paragraphs on the screen. The bilinguals read half of the novel in their first language, and the other half in their second language. In this article, we describe the distributions and descriptive statistics of the most important reading time measures for the two groups of participants. This large eyetracking corpus is perfectly suited for both exploratory purposes and more directed hypothesis testing, and it can guide the formulation of ideas and theories about naturalistic reading processes in a meaningful context. Most importantly, this corpus has the potential to evaluate the generalizability of monolingual and bilingual language theories and models to the reading of long texts and narratives. The corpus is freely available at http://expsy.ugent.be/downloads/geco . PMID- 27193158 TI - ASL-LEX: A lexical database of American Sign Language. AB - ASL-LEX is a lexical database that catalogues information about nearly 1,000 signs in American Sign Language (ASL). It includes the following information: subjective frequency ratings from 25-31 deaf signers, iconicity ratings from 21 37 hearing non-signers, videoclip duration, sign length (onset and offset), grammatical class, and whether the sign is initialized, a fingerspelled loan sign, or a compound. Information about English translations is available for a subset of signs (e.g., alternate translations, translation consistency). In addition, phonological properties (sign type, selected fingers, flexion, major and minor location, and movement) were coded and used to generate sub-lexical frequency and neighborhood density estimates. ASL-LEX is intended for use by researchers, educators, and students who are interested in the properties of the ASL lexicon. An interactive website where the database can be browsed and downloaded is available at http://asl-lex.org . PMID- 27193160 TI - One algorithm to rule them all? An evaluation and discussion of ten eye movement event-detection algorithms. AB - Almost all eye-movement researchers use algorithms to parse raw data and detect distinct types of eye movement events, such as fixations, saccades, and pursuit, and then base their results on these. Surprisingly, these algorithms are rarely evaluated. We evaluated the classifications of ten eye-movement event detection algorithms, on data from an SMI HiSpeed 1250 system, and compared them to manual ratings of two human experts. The evaluation focused on fixations, saccades, and post-saccadic oscillations. The evaluation used both event duration parameters, and sample-by-sample comparisons to rank the algorithms. The resulting event durations varied substantially as a function of what algorithm was used. This evaluation differed from previous evaluations by considering a relatively large set of algorithms, multiple events, and data from both static and dynamic stimuli. The main conclusion is that current detectors of only fixations and saccades work reasonably well for static stimuli, but barely better than chance for dynamic stimuli. Differing results across evaluation methods make it difficult to select one winner for fixation detection. For saccade detection, however, the algorithm by Larsson, Nystrom and Stridh (IEEE Transaction on Biomedical Engineering, 60(9):2484-2493,2013) outperforms all algorithms in data from both static and dynamic stimuli. The data also show how improperly selected algorithms applied to dynamic data misestimate fixation and saccade properties. PMID- 27193159 TI - Sentiment Analysis and Social Cognition Engine (SEANCE): An automatic tool for sentiment, social cognition, and social-order analysis. AB - This study introduces the Sentiment Analysis and Cognition Engine (SEANCE), a freely available text analysis tool that is easy to use, works on most operating systems (Windows, Mac, Linux), is housed on a user's hard drive (as compared to being accessed via an Internet interface), allows for batch processing of text files, includes negation and part-of-speech (POS) features, and reports on thousands of lexical categories and 20 component scores related to sentiment, social cognition, and social order. In the study, we validated SEANCE by investigating whether its indices and related component scores can be used to classify positive and negative reviews in two well-known sentiment analysis test corpora. We contrasted the results of SEANCE with those from Linguistic Inquiry and Word Count (LIWC), a similar tool that is popular in sentiment analysis, but is pay-to-use and does not include negation or POS features. The results demonstrated that both the SEANCE indices and component scores outperformed LIWC on the categorization tasks. PMID- 27193161 TI - Investigations of metastable Ca2IrO4 epitaxial thin-films: systematic comparison with Sr2IrO4 and Ba2IrO4. AB - We have synthesized thermodynamically metastable Ca2IrO4 thin-films on YAlO3 (110) substrates by pulsed laser deposition. The epitaxial Ca2IrO4 thin-films are of K2NiF4-type tetragonal structure. Transport and optical spectroscopy measurements indicate that the electronic structure of the Ca2IrO4 thin-films is similar to that of Jeff = 1/2 spin-orbit-coupled Mott insulator Sr2IrO4 and Ba2IrO4, with the exception of an increased gap energy. The gap increase is to be expected in Ca2IrO4 due to its increased octahedral rotation and tilting, which results in enhanced electron-correlation, U/W. Our results suggest that the epitaxial stabilization growth of metastable-phase thin-films can be used effectively for investigating layered iridates and various complex-oxide systems. PMID- 27193163 TI - A cross-sectional study of the association between mobility test performance and personality among older adults. AB - BACKGROUND: Falls among the elderly are a major public health challenge. The Timed-Up and Go (TUG) test is commonly used to identify older adults with mobility limitations. This study explored the association between TUG test results and personality among community-dwelling older adults. METHODS: This cross-sectional study included 85 older adults. Personality was evaluated with the Five Factor Model. Times to complete the TUG as a single task (TUGST) alone and also with an additional cognitive task i.e., dual-task (DT), were recorded. Ordinary least squares OLS regression models were used to examine the associations between personality factors and both single DT TUG. RESULTS: Extraversion was found to be inversely associated with time to complete the TUGST (beta = -.26, p < .05). Conscientiousness was inversely associated with TUGDT (beta = -.24, p < .01). CONCLUSIONS: Findings from this study highlight the relationship between personality and the TUG test. Specifically, older adults with high Extraversion completed the TUGST test more quickly than those who had lower measures of this trait and, people with high Conscientiousness completed the TUGDT tests more quickly. These findings may contribute to early identification of older adults at higher risk from mobility limitations and falls, and to developing personality-tailored interventions for fall prevention. PMID- 27193164 TI - Cell surface glycans in the human stratum corneum: distribution and depth-related changes. AB - During the formation of the stratum corneum (SC) barrier, the extracellular spaces of viable epidermis, rich in glycans, are filled with a highly organized lipid matrix and the plasma membranes of keratinocytes are replaced by cornified lipid envelopes. These structures comprise cross-linked proteins, including transmembrane glycoproteins and proteoglycans, covalently bound to a monolayer of cell surface ceramides. Little is known about the presence and distribution of glycans on the SC corneocytes despite their possible involvement in SC hydration, cohesion and desquamation. In this work, we visualized ultrastructurally and quantified the distribution of glycans on the surface of native and delipidated corneocytes. The cells were harvested at different depths of the SC, allowing us to define the relationship between the distribution of various glycans, proteoglycans and glycoproteins, and other changes occurring in SC. At the cell periphery, we found a correlation between the depth-related alterations of corneodesmosome glycoproteins and alpha-d-mannosyl and N-acetyl-d-glucosamine labelling patterns. Elimination of the terminal sugars, alpha-linked fucose and alpha-(2,3) linked sialic acid, was less abrupt, but also the initial extent of their peripheral distribution was overall lower than that of concanavalin A and wheat germ agglutinin lectin-detected glycans. Diffuse labelling of heparan sulphate glycosaminoglycans disappeared completely from the outermost corneocytes, whereas that of several simple carbohydrates could be detected at all SC levels. Our results suggest that specific glycan distribution may participate in the progressive changes of SC, as it evolves from the SC compactum to the SC disjunctum, towards desquamation. PMID- 27193162 TI - Transvaginal uterosacral ligament hysteropexy: a retrospective feasibility study. AB - INTRODUCTION AND HYPOTHESIS: Uterine-sparing procedures could be attractive in patients concerned about preservation of fertility and change in corporeal image and sexuality. Transvaginal uterosacral hysteropexy can provide an alternative mesh-free technique for uterine suspension. This study aimed to evaluate the feasibility of transvaginal uterine suspension to uterosacral ligaments in terms of operative data, complications, midterm efficacy, and patient satisfaction. MATERIALS AND METHODS: This retrospective study analyzed the first 20 cases of transvaginal hysteropexy through bilateral high uterosacral ligaments (modified Shull technique) performed in our Institution. RESULTS: Mean follow-up was 33.2 months. The procedure was performed in 84 +/- 19 min ,and blood loss was 228 +/- 139 ml. Three mild complications (15 %) were observed. Recurrence [Pelvic Organ Prolapse Quantification system (POP-Q) stage >= II was observed in five patients (25 %), and three of them (15 %) required reintervention. Mean Patient Global Impression of Improvement score was "much improved." Two woman (40 %) who had not fulfilled their childbearing desire obtained a pregnancy. Both underwent elective caesarean section at term. CONCLUSIONS: Transvaginal uterosacral hysteropexy appears a feasible mesh-free technique for apical support. This procedure can be indicated in women with the desire of preserving fertility or who prefer a uterine-sparing surgical option. PMID- 27193165 TI - A partial trace amine-associated receptor 1 agonist exhibits properties consistent with a methamphetamine substitution treatment. AB - Recent evidence suggests that the trace amine-associated receptor 1 (TAAR1) plays a pivotal role in the regulation of dopamine (DA) transmission and psychostimulant action. Several selective TAAR1 agonists have previously shown efficacy in models of cocaine addiction. However, the effects of TAAR1 activation on methamphetamine (METH)-induced behaviours are less well understood, as indeed are the underlying neurochemical mechanisms mediating potential interactions between TAAR1 and METH. Here, in a progressive ratio schedule of reinforcement the partial TAAR1 agonist, RO5263397, reduced the break-point for METH self administration, while significantly increasing responding maintained by food reward. Following self-administration and extinction training, RO5263397 completely blocked METH-primed reinstatement of METH seeking. Moreover, when used as a substitute, unlike a low dose of METH, which sustained vigorous responding when substituting for the training dose of METH, RO5263397 was not self administered at any dose, thus exhibiting no apparent abuse liability. Fast-scan cyclic voltammetry experiments showed that RO5263397 prevented METH-induced DA overflow in slices of the nucleus accumbens, while having no effect on DA transmission in its own right. Collectively, the present observations demonstrate that partial TAAR1 activation decreases the motivation to self-administer METH, blocks METH-primed reinstatement of METH seeking and prevents METH-induced DA elevations in the nucleus accumbens, and strongly support the candidacy of TAAR1 based medications as potential substitute treatment in METH addiction. PMID- 27193166 TI - BESTROPHIN1 mutations cause defective chloride conductance in patient stem cell derived RPE. AB - Bestrophin1 (BEST1) is expressed in human retinal pigment epithelium (RPE) and mutations in the BEST1 gene commonly cause retinal dysfunction and macular degeneration. BEST1 is presumed to assemble into a calcium-activated chloride channel and be involved in chloride transport but there is no direct evidence in live human RPE cells to support this idea. To test whether BEST1 functions as a chloride channel in living tissue, BEST1-mutant RPE (R218H, L234P, A243T) were generated from patient-derived induced pluripotent stem cells and compared with wild-type RPE in a retinal environment, using a biosensor that visualizes calcium induced chloride ion flux in the cell. Calcium stimulation elicited chloride ion export in normal RPE but not in RPE derived from three patients with BEST1 mutations. These data, along with three-dimensional modeling, provide evidence that BEST1 assembles into a key calcium-sensing chloride channel in human RPE. PMID- 27193168 TI - Altered RNA metabolism due to a homozygous RBM7 mutation in a patient with spinal motor neuropathy. AB - The exosome complex is the most important RNA processing machinery within the cell. Mutations in its subunits EXOSC8 and EXOSC3 cause pontocerebellar hypoplasia, spinal muscular atrophy (SMA) and central nervous system demyelination. We present a patient with SMA-like phenotype carrying a homozygous mutation in RBM7-a subunit of the nuclear exosome targeting (NEXT) complex-which is known to bind and carry specific subtypes of coding and non-coding RNAs to the exosome. The NEXT complex with other protein complexes is responsible for the substrate specificity of the exosome. We performed RNA-sequencing (RNA-seq) analysis on primary fibroblasts of patients with mutations in EXOSC8 and RBM7 and gene knock-down experiments using zebrafish as a model system. RNA-seq analysis identified significantly altered expression of 62 transcripts shared by the two patient cell lines. Knock-down of rbm7, exosc8 and exosc3 in zebrafish showed a common pattern of defects in motor neurons and cerebellum. Our data indicate that impaired RNA metabolism may underlie the clinical phenotype by fine tuning gene expression which is essential for correct neuronal differentiation. PMID- 27193169 TI - Molecular cloning and characterization of the MsHSP17.7 gene from Medicago sativa L. AB - Heat shock proteins (HSPs) are ubiquitous protective proteins that play crucial roles in plant development and adaptation to stress, and the aim of this study is to characterize the HSP gene in alfalfa. Here we isolated a small heat shock protein gene (MsHSP17.7) from alfalfa by homology-based cloning. MsHSP17.7 contains a 477-bp open reading frame and encodes a protein of 17.70-kDa. The amino acid sequence shares high identity with MtHSP (93.98 %), PsHSP17.1 (83.13 %), GmHSP17.9 (74.10 %) and SlHSP17.6 (79.25 %). Phylogenetic analysis revealed that MsHSP17.7 belongs to the group of cytosolic class II small heat shock proteins (sHSP), and likely localizes to the cytoplasm. Quantitative RT-PCR indicated that MsHSP17.7 was induced by heat shock, high salinity, peroxide and drought stress. Prokaryotic expression indicated that the salt and peroxide tolerance of Escherichia coli was remarkably enhanced. Transgenic Arabidopsis plants overexpressing MsHSP17.7 exhibited increased root length of transgenic Arabidopsis lines under salt stress compared to the wild-type line. The malondialdehyde (MDA) levels in the transgenic lines were significantly lower than in wild-type, although proline levels were similar between transgenic and wild-type lines. MsHSP17.7 was induced by heat shock, high salinity, oxidative stress and drought stress. Overexpression analysis suggests that MsHSP17.7 might play a key role in response to high salinity stress. PMID- 27193167 TI - Oxygen consumption deficit in Huntington disease mouse brain under metabolic stress. AB - In vivo evidence for brain mitochondrial dysfunction in animal models of Huntington disease (HD) is scarce. We applied the novel 17O magnetic resonance spectroscopy (MRS) technique on R6/2 mice to directly determine rates of oxygen consumption (CMRO2) and assess mitochondrial function in vivo Basal respiration and maximal CMRO2 in the presence of the mitochondrial uncoupler dinitrophenol (DNP) were compared using 16.4 T in isoflurane anesthetized wild type (WT) and HD mice at 9 weeks. At rest, striatal CMRO2 of R6/2 mice was equivalent to that of WT, indicating comparable mitochondrial output despite onset of motor symptoms in R6/2. After DNP injection, the maximal CMRO2 in both striatum and cortex of R6/2 mice was significantly lower than that of WT, indicating less spare energy generating capacity. In a separate set of mice, oligomycin injection to block ATP generation decreased CMRO2 equally in brains of R6/2 and WT mice, suggesting oxidative phosphorylation capacity and respiratory coupling were equivalent at rest. Expression levels of representative mitochondrial proteins were compared from harvested tissue samples. Significant differences between R6/2 and WT included: in striatum, lower VDAC and the mitochondrially encoded cytochrome oxidase subunit I relative to actin; in cortex, lower tricarboxylic acid cycle enzyme aconitase and higher protein carbonyls; in both, lower glycolytic enzyme enolase. Therefore in R6/2 striatum, lowered CMRO2 may be attributed to a decrease in mitochondria while the cortical CMRO2 decrease may result from constraints upstream in energetic pathways, suggesting regionally specific changes and possibly rates of metabolic impairment. PMID- 27193171 TI - Combined Intraoral and Endoscopic Approach for Malar Reduction. PMID- 27193170 TI - Karyotype diversity suggests that Laonastes aenigmamus (Laotian rock rat) (Rodentia, Diatomyidae) is a multi-specific genus. AB - Laonastes aenigmamus (Khanyou) is a recently described rodent species living in geographically separated limestone formations of the Khammuan Province in Lao PDR. Chromosomes of 21 specimens of L. aenigmamus were studied using chromosome banding as well as fluorescent in situ hybridization (FISH) techniques using human painting, telomere repeats, and 28S rDNA probes. Four different karyotypes were established. Study with human chromosome paints and FISH revealed that four large chromosomes were formed by multiple common tandem fusions, with persistence of some interstitial telomeres. The rearrangements separating the different karyotypes (I to IV) were also reconstructed. Various combinations of Robertsonian translocations or tandem fusions involving the same chromosomes differentiate these karyotypes. These rearrangements create a strong gametic barrier, which isolates specimens with karyotype II from the others. C-banding and FISH with telomere repeats also exhibit large and systematized differences between karyotype II and others. These data indicate an ancient reproductive separation and suggest that Laonastes is not a mono-specific genus. PMID- 27193172 TI - Achieving Ideal Lower Face Aesthetic Contours: Combination of Tridimensional Fat Grafting to the Chin with Masseter Botulinum Toxin Injection. AB - BACKGROUND: Lower face aesthetic contouring is in high demand among Asians with wide and short faces desiring a slim lower face. For this purpose invasive mandible angle reduction and genioplasty are complex procedures with significant risks and downtime. Non-invasive botulinum toxin A injection into bilateral masseters - while popular for lower face contouring - does not address facial length deficiency in wide and short faces. Autologous chin fat grafting is a simple minimally-invasive technique for facial lengthening. OBJECTIVES: We present our experience pairing chin fat grafting and masseteric botulinum toxin injection for effective lower face contouring. METHODS: Thirteen consecutive patients with relatively wide and short faces underwent chin fat grafting and 1 to 3 serial masseteric botulinum toxin A injections. Mean follow up after final intervention was 20 months (range, 6 months to 3 years). RESULTS: The postoperative mean ratio of bigonial distance to total facial height improved from 0.599 to 0.569 (P < .01), closer to the ideal ratio of 0.561. The mean ratio of upper lip length to lower lip and chin length improved from 0.611 to 0.560 (P < .01), nearing the ideal 0.542. Postoperative lateral profile in all was ideal. There were no complications at follow up. Results were durable at latest follow up and most were satisfied with their final appearance. CONCLUSIONS: Combined tridimensional chin fat grafting and botulinum toxin masseteric injection is an effective, simple, fast, inexpensive, safe, and minimally-invasive strategy for aesthetic lower face contouring of short and wide faces, with short downtime, long-lasting results, and high patient satisfaction. LEVEL OF EVIDENCE: 4 Therapeutic. PMID- 27193173 TI - How Social Are We? A Cross-Sectional Study of the Website Presence and Social Media Activity of Canadian Plastic Surgeons. AB - The internet and social media are increasingly being used by patients not only for health-related research, but also for obtaining information on their surgeon. Having an online presence via a website and social media profile is one-way plastic surgeons can meet this patient driven demand. The authors sought to document current website and social media usage of Canadian plastic surgeons and to determine if this usage correlated with years in practice. A Google search was performed using publicly available lists of all plastic surgeons registered with the Royal College of Physicians and Surgeons of Canada (RCPSC) and the Canadian Society for Aesthetic Plastic Surgery (CSAPS). This search found 42% (268/631) of RCPSC plastic surgeons had a website and 85% (536/631) had a profile on social media. Younger RCPSC surgeons (registered for less years) were significantly more likely to have a website (12.8 vs. 21.9 years, P < 0.0001) and an active social media profile (16.2 vs. 23.9 years, P < 0.002). The social media platform most used was RateMDs (81%) followed in decreasing order by: LinkedIn (28%), RealSelf (22%), Facebook (20%), Google+ (17%) and Twitter (16%). Dual RCPSC-CSAPS members were more likely than RCPSC-only members to have a website (56 vs. 36%, P < 0.0001) and an active social media profile (P < 0.05). Overall, current website usage and social media presence by Canadian plastic surgeons is comparable to counterparts in the US and UK. It may be possible to better optimize online presence through education of current search engine technology and becoming active on multiple social media platforms. PMID- 27193176 TI - Editors' note. PMID- 27193175 TI - Identification of impaired fasting glucose, healthcare utilization and progression to diabetes in the UK using the Clinical Practice Research Datalink (CPRD). AB - PURPOSE: Few studies have examined patients with prediabetes in usual, "real world" clinical practice settings. Among patients with impaired fasting glucose (IFG), we aimed to describe the rates of progression to diabetes and to examine the long-term reduction in diabetes risk associated with regression to normoglycemia at 1 year. METHODS: The UK-based study included 120 055 non diabetic patients in Clinical Practice Research Datalink from 2001 to 2012 aged 25+ years and with >=1 fasting plasma glucose (FPG) test between >=6.1 and <7.0 mmol/l indicating IFG who were followed for progression to diabetes. In a subgroup of 45 167 patients with IFG with subsequent FPG results 1 year later, we assessed the 1-year glycemic status change and estimated the relative hazard of diabetes comparing patients with regression to normoglycemia (IFG-normoglycemia) to those who remained in IFG (IFG-IFG) using a multivariable Cox model. RESULTS: Among patients with IFG with over 414 649 person-years of follow-up, 52% received a subsequent FPG test, and 10% developed diabetes within 1 year after recognition of IFG. The incidence rate of diabetes was 5.86 (95% CI: 5.78 to 5.93) per 100 person-years. In the subgroup analysis, 31% of these patients remained in IFG, while 53% and 16% converted to normoglycemia or diabetes, respectively. The adjusted hazard ratio of developing diabetes was 0.33 (95% CI: 0.31 to 0.35) comparing IFG-normoglycemia to IFG-IFG. CONCLUSIONS: IFG is a high-risk state for diabetes. Regression to normoglycemia from IFG strongly reduces the long-term risk of developing diabetes. Our study also shows the feasibility of identifying patients with IFG in the Clinical Practice Research Datalink. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27193177 TI - Spinal Cord Injury (SCI) Facts and Figures at a Glance. PMID- 27193174 TI - Apigenin reduce lipoteichoic acid-induced inflammatory response in rat cardiomyoblast cells. AB - Infective endocarditis is caused by Streptococcus sanguinis present in dental plaque, which can induce inflammatory responses in the endocardium. The present study depicts research on the properties of apigenin in embryonic mouse heart cells (H9c2) treated with lipoteichoic acid (LTA) obtained from S. sanguinis. Interleukin-1beta and cyclooxygenase (COX)-2 expression were detected by reverse transcriptase polymerase chain reaction. In addition, western blot assays and immuno-fluorescence staining were used to assess translocation of nuclear factor kappa beta (NF-kappaB), degradation of IkappaB, as well as activity of the mitogen activated protein kinases: extracellular signal-regulated kinase (ERK)1/2, p38, and c-Jun N-terminal kinase (JNK). Effect of apigenin on cell viability was equally assessed in other experimental series. Our results showed that apigenin blocked activation of ERK, JNK, and p38 in cardiomyocytes treated with LTA in a dose-dependent fashion. Moreover, apigenin showed no cytotoxic effects; it blocked NF-kappaB translocation and IkappaB degradation. Our findings suggested that apigenin possessed potential value in the treatment of infectious endocarditis. PMID- 27193178 TI - Radiobiological influence of megavoltage electron pulses of ultra-high pulse dose rate on normal tissue cells. AB - Regarding the long-term goal to develop and establish laser-based particle accelerators for a future radiotherapeutic treatment of cancer, the radiobiological consequences of the characteristic short intense particle pulses with ultra-high peak dose rate, but low repetition rate of laser-driven beams have to be investigated. This work presents in vitro experiments performed at the radiation source ELBE (Electron Linac for beams with high Brilliance and low Emittance). This accelerator delivered 20-MeV electron pulses with ultra-high pulse dose rate of 10(10) Gy/min either at the low pulse frequency analogue to previous cell experiments with laser-driven electrons or at high frequency for minimizing the prolonged dose delivery and to perform comparison irradiation with a quasi-continuous electron beam analogue to a clinically used linear accelerator. The influence of the different electron beam pulse structures on the radiobiological response of the normal tissue cell line 184A1 and two primary fibroblasts was investigated regarding clonogenic survival and the number of DNA double-strand breaks that remain 24 h after irradiation. Thereby, no considerable differences in radiation response were revealed both for biological endpoints and for all probed cell cultures. These results provide evidence that the radiobiological effectiveness of the pulsed electron beams is not affected by the ultra-high pulse dose rates alone. PMID- 27193179 TI - Case report: a patient with pulmonary arterial hypertension transitioning from a PDE-5 inhibitor to Riociguat. AB - BACKGROUND: We present here the case of a patient with pulmonary arterial hypertension and NYHA Class II symptoms who transitioned from PDE-5i therapy to riociguat. No protocol currently exists for transitioning between these PAH medications. CASE PRESENTATION: A 59-year old male with a history of anorexigen use initially presented in 2008 and was felt to have non-operable small vessel disease. His care was transitioned to our center after insurance would not cover high-dose sildenafil in addition to ERA therapy. CONCLUSION: This case demonstrates a safe and successful transition from higher dose PDE-5is to riociguat with no interruption in therapy. PMID- 27193180 TI - Molecular pathogenesis of plasminogen Hakodate: the second Japanese family case of severe type I plasminogen deficiency manifested late-onset multi-organic chronic pseudomembranous mucositis. AB - A 64-year-old man first developed ligneous conjunctivitis at the age of 58 years after right pulmonary resection because of suspected cancer; otherwise, he had been healthy. Since then, he began to suffer from various forms of chronic pseudomembranous mucositis. Laboratory tests demonstrated that he had 7.8 % of plasminogen activity and 5.9 % of the normal antigen level. Thus, he was diagnosed as having severe type I plasminogen deficiency, making him the third case in Japan. DNA sequencing and PCR-restriction fragment length polymorphism analyses revealed that this patient was a compound heterozygote of a G-to-A missense mutation (G266E) in exon VIII and a g-to-a mutation at the obligatory splicing acceptor site in intron 12 (IVS12-1g>a). These two mutations were confirmed to be novel. Molecular modeling and splice site strength calculation predicted conformational disorder(s) for the Glu266 mutant and a drastic decrease in splicing efficiency for intron 12, respectively. Western blot analysis demonstrated that the patient contained a small amount of the normal-sized plasminogen protein. Mass spectrometric analysis of the patient's plasminogen revealed a peptide containing the wild-type Gly266 residue and no peptides with mutations at Glu266. However, he had never suffered from thrombosis. Low levels of fibrinogen/fibrin degradation products (FDP), D-dimer, and plasmin-alpha2 plasmin inhibitor complex clearly indicated a hypo-fibrinolytic condition. However, his plasma concentration of elastase-digested crosslinked FDPs was 4.8 U/mL, suggesting the presence of an on-going plasmin(ogen)-independent "alternative" fibrinolytic system, which may protect the patient from thrombosis. The patient has been free from recurrence of ligneous conjunctivitis for approximately 2.5 years. PMID- 27193181 TI - II. Dissociation free energies in drug-receptor systems via nonequilibrium alchemical simulations: application to the FK506-related immunophilin ligands. AB - The recently proposed fast switching double annihilation (FS-DAM) [Cardelli et al., J. Chem. Theory Comput., 2015, 11, 423] is aimed at computing the absolute standard dissociation free energies for the chemical equilibrium RL ? R + L occurring in solution through molecular dynamics (MD) simulations at the atomistic level. The technique is based on the production of fast nonequilibrium annihilation trajectories of one of the species (the ligand) in the solvated RL complex and in the bulk solvent. As detailed in the companion theoretical paper, the free energies of these two nonequilibrium annihilation processes are recovered by using an unbiased unidirectional estimate derived from the Crooks theorem exploiting the inherent Gaussian nature of the annihilation work. The FS DAM technique was successfully applied to the evaluation of the dissociation free energy of the complexes of Zn(ii) cations with an inhibitor of the Tumor Necrosis Factor alpha converting enzyme. Here we apply the technique to a real drug receptor system, by satisfactorily reproducing the experimental dissociation free energies of FK506-related bulky ligands towards the native FKBP12 enzyme and by predicting the dissociation constants for the same ligands towards the mutant I56D. The effect of such mutations on the binding affinity of FK506-related ligands is relevant for assessing the thermodynamic forces regulating molecular recognition in FKBP12 inhibition. PMID- 27193182 TI - Sexuality and Autistic-Like Symptoms in Juvenile Sex Offenders: A Follow-Up After 8 Years. AB - Juveniles who have committed a sexual offense (JSOs) are thought to have abnormal sexual development, as well as increased ASD symptoms. In the current study, sexual development and behavior, as well as stability of ASD-like symptoms were assessed in a sample of 44 male JSOs (mean age 24.7 +/- 1.5 years) 8 years after their sexual offence. JSOs exhibited less knowledge of sexuality, less positive attitudes towards pornography and more often reported having been a victim of verbal sexual intimidation than a matched normal population sample. ASD symptoms were relatively stable over the 8 years follow-up, indicating that social difficulties in JSOs may be part of life-long autistic-like traits. However, ASD symptoms were not related to alterations in sexual development or behavior. PMID- 27193183 TI - After Early Autism Diagnosis: Changes in Intervention and Parent-Child Interaction. AB - This study documents the relation between an autism spectrum disorder (ASD) diagnosis, increases in intervention, and changes in parent-child interaction quality. Information about intervention and observations of interaction were collected before diagnosis and a half year after diagnosis for 79 low-risk toddlers who had screened positive for ASD risk during a well-baby checkup. Children diagnosed with ASD (n = 44) were 2.69 times more likely to increase intervention hours. After ASD diagnosis, the relation between intervention and interaction quality was complex: although increases in intervention and interaction quality were only modestly related, the overall amount of intervention after diagnosis was associated with higher quality interactions. Moreover, lower quality interactions before diagnosis significantly increased the likelihood that intervention would increase post-diagnosis. PMID- 27193184 TI - Brief Report: Simulations Suggest Heterogeneous Category Learning and Generalization in Children with Autism is a Result of Idiosyncratic Perceptual Transformations. AB - Children with autism spectrum disorder (ASD) sometimes have difficulties learning categories. Past computational work suggests that such deficits may result from atypical representations in cortical maps. Here we use neural networks to show that idiosyncratic transformations of inputs can result in the formation of feature maps that impair category learning for some inputs, but not for other closely related inputs. These simulations suggest that large inter- and intra individual variations in learning capacities shown by children with ASD across similar categorization tasks may similarly result from idiosyncratic perceptual encoding that is resistant to experience-dependent changes. If so, then both feedback- and exposure-based category learning should lead to heterogeneous, stimulus-dependent deficits in children with ASD. PMID- 27193185 TI - A proposal of a simple epidural simulator for training novice anesthesiologists. AB - PURPOSE: Confirming the epidural space during epidural anesthesia relies mainly on feel and experience, which are difficult techniques for a trainee to learn. We designed an epidural simulator for trainees to experience loss of resistance (LOR) and various degrees of pressure resistance. METHODS: The simulator consists of a Perifix((r)) LOR syringe and 1-, 5-, 10- and 50-mL syringes assembled by three-way stopcocks. A total of 89 anesthesiologists evaluated the simulator, given the choice of either the intermittent technique with air or continuous technique with saline. Sudden LOR and applicability of the simulator for training purposes were assessed using the numerical rating score (NRS). Pressure resistance at each lumbar structure was evaluated by the anesthesiologists using the intermittent technique with air. RESULTS: Seventy-four anesthesiologists used the intermittent technique with air and 15 used the continuous technique with saline. The NRSs for sudden LOR and the applicability for training purposes were 8 and 9 (median), respectively. The pressure resistance to a 50-mL syringe was regarded as the epidural space (odds ratio 602.3 for 5-mL syringe and 144.4 for 10-mL syringe) by 89 % of anesthesiologists using air for LOR. Resistance to the 10-mL syringe was most frequently considered as muscle, subcutaneous fat, or the interspinous ligament, while resistance to the 1-mL syringe was considered as the ligamentum flavum (odds ratio 2.3 for 5-mL syringe and 18.6 for 10-mL syringe). CONCLUSIONS: Our epidural simulator is a simple, low-cost device that can be easily constructed. It was shown to provide valid haptic feedback as a promising tool for training novice anesthesiologists. PMID- 27193186 TI - The Essential Role of H19 Contributing to Cisplatin Resistance by Regulating Glutathione Metabolism in High-Grade Serous Ovarian Cancer. AB - Primary and acquired drug resistance is one of the main obstacles encountered in high-grade serous ovarian cancer (HGSC) chemotherapy. Cisplatin induces DNA damage through cross-linking and long integrated non-coding RNAs (lincRNAs) play an important role in chemical induced DNA-damage response, which suggests that lincRNAs may be also associated with cisplatin resistance. However, the mechanism of long integrated non-coding RNAs (lincRNAs) acting on cisplatin resistance is not well understood. Here, we showed that expression of lin-RECK-3, H19, LUCAT1, LINC00961, and linc-CARS2-2 was enhanced in cisplatin-resistant A2780-DR cells, while transcriptome sequencing showed decreased Linc-TNFRSF19-1 and LINC00515 expression. Additionally, we verified that different H19 expression levels in HGSC tissues showed strong correlation with cancer recurrence. H19 knockdown in A2780-DR cells resulted in recovery of cisplatin sensitivity in vitro and in vivo. Quantitative proteomics analysis indicated that six NRF2-targeted proteins, including NQO1, GSR, G6PD, GCLC, GCLM and GSTP1 involved in the glutathione metabolism pathway, were reduced in H19-knockdown cells. Furthermore, H19 knockdown cells were markedly more sensitive to hydrogen-peroxide treatment and exhibited lower glutathione levels. Our results reveal a previously unknown link between H19 and glutathione metabolism in the regulation of cancer-drug resistance. PMID- 27193188 TI - Reward-related neural dysfunction across depression and impulsivity: A dimensional approach. AB - Recent theoretical models underline reward sensitivity as a potential endophenotype for major depressive disorder. Neural and behavioral evidence reveals depression is associated with reduced reward sensitivity. However, reward dysfunction is not unique to depression, as it is also common across disorders of poor impulse control. We examined the interrelationships of depression (Depression, Anxiety, and Stress Scale [DASS-21]) and impulsivity (UPPS-P Impulsive Behavior Scale) with reward sensitivity among a large, representative sample (N = 260). ERPs were recorded to isolate two neural indicators of consummatory reward processing: initial evaluation of rewards in the 250-350 ms time window postonset of feedback (reward positivity [RewP]), and salience to monetary outcomes (P3). Significant interactions were observed between depression and impulsivity facets across these two stages of reward processing: depression and positive urgency predicted RewP amplitude to reward outcomes (win vs. loss); depression and one other impulsivity trait, (lack of) premeditation, predicted P3 amplitude to monetary outcomes. Conversely, high symptoms of depression were related to three biobehavioral profiles: (1) blunted RewP in conjunction with high positive urgency, (2) combination of blunted RewP and low (lack of) premeditation, and (3) blunted P3 to monetary wins/losses, in conjunction with low (lack of) premeditation. Findings illustrate that reward-related dysfunctions may be optimally conceptualized when examining the interactions between dimensions of internalizing and externalizing psychopathology. PMID- 27193187 TI - Internet Gaming Disorder as a formative construct: Implications for conceptualization and measurement. AB - Some people have serious problems controlling their Internet and video game use. The DSM-5 now includes a proposal for 'Internet Gaming Disorder' (IGD) as a condition in need of further study. Various studies aim to validate the proposed diagnostic criteria for IGD and multiple new scales have been introduced that cover the suggested criteria. Using a structured approach, we demonstrate that IGD might be better interpreted as a formative construct, as opposed to the current practice of conceptualizing it as a reflective construct. Incorrectly approaching a formative construct as a reflective one causes serious problems in scale development, including: (i) incorrect reliance on item-to-total scale correlation to exclude items and incorrectly relying on indices of inter-item reliability that do not fit the measurement model (e.g., Cronbach's alpha); (ii) incorrect interpretation of composite or mean scores that assume all items are equal in contributing value to a sum score; and (iii) biased estimation of model parameters in statistical models. We show that these issues are impacting current validation efforts through two recent examples. A reinterpretation of IGD as a formative construct has broad consequences for current validation efforts and provides opportunities to reanalyze existing data. We discuss three broad implications for current research: (i) composite latent constructs should be defined and used in models; (ii) item exclusion and selection should not rely on item-to-total scale correlations; and (iii) existing definitions of IGD should be enriched further. PMID- 27193189 TI - Management of Perforator Plunge in the Transverse Sinus. AB - Plunging is rare with the use of automatic-release perforators. We describe the management of a case of plunging in the transverse sinus in a child who underwent suboccipital craniotomy. The perforator got stuck in the bone and transverse sinus. The perforator-bone complex was removed in one piece with suturing of the transverse sinus. PMID- 27193191 TI - Nanomaterial-modulated autophagy: underlying mechanisms and functional consequences. AB - Autophagy is an essential lysosome-dependent process that controls the quality of the cytoplasm and maintains cellular homeostasis, and dysfunction of this protein degradation system is correlated with various disorders. A growing body of evidence suggests that nanomaterials (NMs) have autophagy-modulating effects, thus predicting a valuable and promising application potential of NMs in the diagnosis and treatment of autophagy-related diseases. NMs exhibit unique physical, chemical and biofunctional properties, which may endow NMs with capabilities to modulate autophagy via various mechanisms. The present review highlights the impacts of various NMs on autophagy and their functional consequences. The possible underlying mechanisms for NM-modulated autophagy are also discussed. PMID- 27193192 TI - Sacral nerve stimulation for faecal incontinence: medium-term follow-up from a single institution. AB - BACKGROUND: Most studies on sacral nerve stimulation (SNS) are either single centre with small numbers of patients or multi-centre studies. We present the medium-term follow-up results from a single centre for 127 patients undergoing SNS. METHODS: Consecutive patients treated with SNS for faecal incontinence had preoperative baseline St Mark's continence scores, faecal incontinence quality of life (FIQL) measures and anorectal physiology studies. Follow-up was a postal questionnaire concerning continence, FIQL, patient-perceived change in bowel control (-5 to +5 where 0 is no change), overall satisfaction (0-10 visual analogue scale) and use of medications. RESULTS: A total of 166 patients underwent temporary nerve stimulation testing, of which 112 progressed to a permanent implantable pulse generator (IPG). Fifteen received an IPG without the testing phase, hence 127 patients in total. Fourteen had the IPG removed, four were deceased, leaving 109 for assessment; 91 (83%) responded to the survey. Mean follow-up was 2.7 years (range: 2 months-8.5 years). Mean baseline St Mark's continence score was 14.4, and mean follow-up score was 10.3 (P < 0.01). FIQL improved in all domains (P < 0.001). Patient-reported improved bowel control mean score was +3.2 (95% CI: 2.9, 3.55). Median satisfaction score was 8.0 (range: 0 10). Complications included 17 lead dislodgements, seven superficial infections, five infections requiring surgery and five repositioning of a rotated IPG. Thirty two patients used loperamide and 34 used fibre supplements. CONCLUSION: In this observational study, limited by the absence of a placebo control group, SNS significantly improved continence and quality of life, and patient satisfaction was high. PMID- 27193193 TI - Atomic structure of a peptide coated gold nanocluster identified using theoretical and experimental studies. AB - Peptide coated gold nanoclusters (AuNCs) have a precise molecular formula and atomic structure, which are critical for their unique applications in targeting specific proteins either for protein analysis or drug design. To date, a study of the crystal structure of peptide coated AuNCs is absent primarily due to the difficulty of obtaining their crystalline phases in an experiment. Here we study a typical peptide coated AuNC (Au24Peptide8, Peptide = H2N-CCYKKKKQAGDV-COOH, Anal. Chem., 2015, 87, 2546) to figure out its atomic structure and electronic structure using a theoretical method for the first time. In this work, we identify the explicit configuration of the essential structure of Au24Peptide8, Au24(Cys-Cys)8, using density functional theory (DFT) computations and optical spectroscopic experiments, where Cys denotes cysteine without H bonded to S. As the first multidentate ligand binding AuNC, Au24(Cys-Cys)8 is characterized as a distorted Au13 core with Oh symmetry covered by two Au(Cys-Cys) and three Au3(Cys Cys)2 staple motifs in its atomic structure. The most stable configuration of Au24(Cys-Cys)8 is confirmed by comparing its UV-vis absorption spectrum from time dependent density-functional theory (TDDFT) calculations with optical absorption measurements, and these results are consistent with each other. Furthermore, we carry out frontier molecular orbital (FMO) calculations to elucidate that the electronic structure of Au24(Cys-Cys)8 is different from that of Au24(SR)20 as they have a different Au/S ratio, where SR represents alkylthiolate. Importantly, the different ligand coatings, Cys-Cys and SR, in Au24(Cys-Cys)8 and Au24(SR)20 cause the different Au/S ratios in the coated Au24. The reason is that the Au/S ratio is crucial in determining the size of the Au core of the ligand protected AuNC, and the size of the Au core corresponds to a specific electronic structure. By the adjustment of ligand coatings from alkylthiolate to peptide, the Au/S ratio could be controlled to generate different AuNCs with versatile electronic structures, optical properties and reaction stabilities. Therefore, we propose a universal approach to obtain a specific Au/S ratio of ligand coated AuNCs by adjusting the ligand composition, thus controlling the chemicophysical properties of AuNCs with ultimately the same number of Au atoms. PMID- 27193190 TI - The ALS/FTLD associated protein C9orf72 associates with SMCR8 and WDR41 to regulate the autophagy-lysosome pathway. AB - Hexanucleotide repeat expansion in the C9orf72 gene is a leading cause of frontotemporal lobar degeneration (FTLD) with amyotrophic lateral sclerosis (ALS). Reduced expression of C9orf72 has been proposed as a possible disease mechanism. However, the cellular function of C9orf72 remains to be characterized. Here we report the identification of two binding partners of C9orf72: SMCR8 and WDR41. We show that WDR41 interacts with the C9orf72/SMCR8 heterodimer and WDR41 is tightly associated with the Golgi complex. We further demonstrate that C9orf72/SMCR8/WDR41 associates with the FIP200/Ulk1 complex, which is essential for autophagy initiation. C9orf72 deficient mice, generated using the CRISPR/Cas9 system, show severe inflammation in multiple organs, including lymph node, spleen and liver. Lymph node enlargement and severe splenomegaly are accompanied with macrophage infiltration. Increased levels of autophagy and lysosomal proteins and autophagy defects were detected in both the spleen and liver of C9orf72 deficient mice, supporting an in vivo role of C9orf72 in regulating the autophagy/lysosome pathway. In summary, our study elucidates potential physiological functions of C9orf72 and disease mechanisms of ALS/FTLD. PMID- 27193195 TI - Variation in infection length and superinfection enhance selection efficiency in the human malaria parasite. AB - The capacity for adaptation is central to the evolutionary success of the human malaria parasite Plasmodium falciparum. Malaria epidemiology is characterized by the circulation of multiple, genetically diverse parasite clones, frequent superinfection, and highly variable infection lengths, a large number of which are chronic and asymptomatic. The impact of these characteristics on the evolution of the parasite is largely unknown, however, hampering our understanding of the impact of interventions and the emergence of drug resistance. In particular, standard population genetic frameworks do not accommodate variation in infection length or superinfection. Here, we develop a population genetic model of malaria including these variations, and show that these aspects of malaria infection dynamics enhance both the probability and speed of fixation for beneficial alleles in complex and non-intuitive ways. We find that populations containing a mixture of short- and long-lived infections promote selection efficiency. Interestingly, this increase in selection efficiency occurs even when only a small fraction of the infections are chronic, suggesting that selection can occur efficiently in areas of low transmission intensity, providing a hypothesis for the repeated emergence of drug resistance in the low transmission setting of Southeast Asia. PMID- 27193197 TI - Treatments for paracetamol poisoning. PMID- 27193198 TI - Bias in emerging biomarkers for bipolar disorder. AB - BACKGROUND: To date no comprehensive evaluation has appraised the likelihood of bias or the strength of the evidence of peripheral biomarkers for bipolar disorder (BD). Here we performed an umbrella review of meta-analyses of peripheral non-genetic biomarkers for BD. METHOD: The Pubmed/Medline, EMBASE and PsycInfo electronic databases were searched up to May 2015. Two independent authors conducted searches, examined references for eligibility, and extracted data. Meta-analyses in any language examining peripheral non-genetic biomarkers in participants with BD (across different mood states) compared to unaffected controls were included. RESULTS: Six references, which examined 13 biomarkers across 20 meta-analyses (5474 BD cases and 4823 healthy controls) met inclusion criteria. Evidence for excess of significance bias (i.e. bias favoring publication of 'positive' nominally significant results) was observed in 11 meta analyses. Heterogeneity was high for (I 2 ? 50%) 16 meta-analyses. Only two biomarkers met criteria for suggestive evidence namely the soluble IL-2 receptor and morning cortisol. The median power of included studies, using the effect size of the largest dataset as the plausible true effect size of each meta-analysis, was 15.3%. CONCLUSIONS: Our findings suggest that there is an excess of statistically significant results in the literature of peripheral biomarkers for BD. Selective publication of 'positive' results and selective reporting of outcomes are possible mechanisms. PMID- 27193196 TI - Neuromyelitis optica study model based on chronic infusion of autoantibodies in rat cerebrospinal fluid. AB - BACKGROUND: Devic's neuromyelitis optica (NMO) is an autoimmune astrocytopathy, associated with central nervous system inflammation, demyelination, and neuronal injury. Several studies confirmed that autoantibodies directed against aquaporin 4 (AQP4-IgG) are relevant in the pathogenesis of NMO, mainly through complement dependent toxicity leading to astrocyte death. However, the effect of the autoantibody per se and the exact role of intrathecal AQP4-IgG are still controversial. METHODS: To explore the intrinsic effect of intrathecal AQP4-IgG, independent from additional inflammatory effector mechanisms, and to evaluate its clinical impact, we developed a new animal model, based on a prolonged infusion of purified immunoglobulins from NMO patient (IgG(AQP4+), NMO-rat) and healthy individual as control (Control-rat) in the cerebrospinal fluid (CSF) of live rats. RESULTS: We showed that CSF infusion of purified immunoglobulins led to diffusion in the brain, spinal cord, and optic nerves, the targeted structures in NMO. This was associated with astrocyte alteration in NMO-rats characterized by loss of aquaporin-4 expression in the spinal cord and the optic nerves compared to the Control-rats (p = 0.001 and p = 0.02, respectively). In addition, glutamate uptake tested on vigil rats was dramatically reduced in NMO-rats (p = 0.001) suggesting that astrocytopathy occurred in response to AQP4-IgG diffusion. In parallel, myelin was altered, as shown by the decrease of myelin basic protein staining by up to 46 and 22 % in the gray and white matter of the NMO-rats spinal cord, respectively (p = 0.03). Loss of neurofilament positive axons in NMO-rats (p = 0.003) revealed alteration of axonal integrity. Then, we investigated the clinical consequences of such alterations on the motor behavior of the NMO-rats. In a rotarod test, NMO-rats performance was lower compared to the controls (p = 0.0182). AQP4 expression, and myelin and axonal integrity were preserved in AQP4 IgG-depleted condition. We did not find a major immune cell infiltration and microglial activation nor complement deposition in the central nervous system, in our model. CONCLUSIONS: We establish a link between motor-deficit, NMO-like lesions and astrocytopathy mediated by intrathecal AQP4-IgG. Our study validates the concept of the intrinsic effect of autoantibody against surface antigens and offers a model for testing antibody and astrocyte-targeted therapies in NMO. PMID- 27193199 TI - Association between clinical antibiotic resistance and susceptibility of Pseudomonas in the cystic fibrosis lung. AB - BACKGROUND AND OBJECTIVES: Cystic fibrosis patients suffer from chronic lung infections that require long-term antibiotic therapy. Pseudomonas readily evolve resistance, rendering antibiotics ineffective. In vitro experiments suggest that resistant bacteria may be treated by exploiting their collateral sensitivity to other antibiotics. Here, we investigate correlations of sensitivity and resistance profiles of Pseudomonas aeruginosa that naturally adapted to antibiotics in the cystic fibrosis lung. METHODOLOGY: Resistance profiles for 13 antibiotics were obtained using broth dilution, E-test and VITEK mass spectroscopy. Genetic variants were determined from whole-genome sequences and interrelationships among isolates were analyzed using 13 MLST loci. RESULT: Our study focused on 45 isolates from 13 patients under documented treatment with antibiotics. Forty percent of these were clinically resistant and 15% multi-drug resistant. Colistin resistance was found once, despite continuous colistin treatment and even though colistin resistance can readily evolve experimentally in the laboratory. Patients typically harbored multiple genetically and phenotypically distinct clones. However, genetically similar clones often had dissimilar resistance profiles. Isolates showed mutations in genes encoding cell wall synthesis, alginate production, efflux pumps and antibiotic modifying enzymes. Cross-resistance was commonly observed within antibiotic classes and between aminoglycosides and beta-lactam antibiotics. No evidence was found for consistent phenotypic resistance to one antibiotic and sensitivity to another within one genotype. CONCLUSIONS AND IMPLICATIONS: Evidence supporting potential collateral sensitivity in clinical P. aeruginosa isolates remains equivocal. However, cross-resistance within antibiotic classes is common. Colistin therapy is promising since resistance to it was rare despite its intensive use in the studied patients. PMID- 27193201 TI - Clone wars: the evolution of therapeutic resistance in cancer. PMID- 27193200 TI - The low prevalence of female smoking in the developing world: gender inequality or maternal adaptations for fetal protection? AB - BACKGROUND: Female smoking prevalence is dramatically lower in developing countries (3.1%) than developed countries (17.2%), whereas male smoking is similar (32% vs 30.1%). Low female smoking has been linked to high gender inequality. Alternatively, to protect their offspring from teratogenic substances, pregnant and lactating women appear to have evolved aversions to toxic plant substances like nicotine, which are reinforced by cultural proscriptions. Higher total fertility rates (TFRs) in developing countries could therefore explain their lower prevalence of female smoking. OBJECTIVE: To compare the associations of TFR and gender inequality with national prevalence rates of female and male smoking. METHODS: Data from a previous study of smoking prevalence vs gender inequality in 74 countries were reanalysed with a regression model that also included TFR. We replicated this analysis with three additional measures of gender equality and 2012 smoking data from 173 countries. RESULTS: A 1 SD increase in TFR predicted a decrease in female smoking prevalence by factors of 0.58-0.77, adjusting for covariates. TFR had a smaller and unexpected negative association with male smoking prevalence. Increased gender equality was associated with increased female smoking prevalence, and, unexpectedly, with decreased male smoking prevalence. TFR was also associated with an increase in smoking prevalence among postmenopausal women. CONCLUSIONS: High TFR and gender inequality both predict reduced prevalence of female smoking across nations. In countries with high TFR, adaptations and cultural norms that protect fetuses from plant toxins might suppress smoking among frequently pregnant and lactating women. PMID- 27193202 TI - Systematic review with meta-analysis: the effect of tobacco smoking on the natural history of ulcerative colitis. AB - BACKGROUND: Tobacco smoking is associated with a reduced risk of developing ulcerative colitis (UC). A high proportion of UC patients perceive a benefit in disease outcomes secondary to smoking. However, the effects of smoking on the natural history of UC are uncertain. AIM: To conduct a systematic review and meta analysis of the effects of tobacco smoking on the natural history of UC. METHODS: A search of MEDLINE, EMBASE and EMBASE classic was carried out (up to December 2015) to identify observational studies reporting data on smoking and rates of colectomy, flare of disease activity, proximal disease extension, and development of pouchitis following panproctocolectomy and ileal pouch-anal anastomosis in patients with UC. Dichotomous data were pooled to obtain odds ratios (ORs), with 95% confidence intervals (CIs). RESULTS: The search identified 16 eligible studies: five (2615 patients) studying colectomy; four (620 patients) reporting on flare of disease activity; four (687 patients) examining proximal disease extension and three (355 patients) assessing development of pouchitis. Compared with nonsmokers, the odds of colectomy (OR = 0.89; 95% CI 0.62-1.26), flare of disease activity (OR = 1.26; 95% CI 0.65-2.44), proximal extension of disease (OR = 0.57; 95% CI 0.20-1.66) or the development of pouchitis (OR = 0.57; 95% CI 0.21 1.53) were not significantly lower in smokers. CONCLUSIONS: Smoking may not improve the natural history of ulcerative colitis. Given the health benefits of smoking cessation and the lack of clear benefit in ulcerative colitis, smoking cessation advice should be incorporated into guidance on the management of ulcerative colitis. PMID- 27193203 TI - The effect of axial rotation of the anterior resection plane in patellofemoral arthroplasty. AB - BACKGROUND: Patellofemoral arthroplasty (PFA) has a small but definite place in replacement surgery of the knee, especially in young patients. The main surgical considerations in PFA are the patient's anatomy, the type of prosthesis and the surgical technique. The surgical technique and PFA success rely heavily on the anterior resection. In this study we investigate the effect of axial rotation of the anterior resection plane. METHODS: We tested the outcome of PFA fit based on resection footprint measurements, axial and coronal groove angles, and lateral trochlear inclination (LTI) angle in a virtual PFA model. The range of anterior resection plane axial rotations was from five degree internal to five degree external with an increment of one degree. RESULTS: Axial rotation of anterior resection plane changes the resection footprint dimension, which leads to coronal rotation of the femoral component. External rotation of the resection plane results in valgus rotation of the trochlear groove and decreased LTI after PFA and the opposite was observed for internal rotation. CONCLUSION: Our study showed that by changing the axial rotation of the anterior cut, the coronal groove of the prosthesis can be altered to lie more closely with the native groove line without compromising the prosthesis-cartilage transition. PMID- 27193204 TI - [Not Available]. PMID- 27193205 TI - Early synaptic dysfunction in Parkinson's disease: Insights from animal models. AB - The appearance of motor manifestations in Parkinson's disease (PD) is invariably linked to degeneration of nigral dopaminergic neurons of the substantia nigra pars compacta. Traditional views on PD neuropathology have been grounded in the assumption that the prime event of neurodegeneration involves neuronal cell bodies with the accumulation of metabolic products. However, this view has recently been challenged by both clinical and experimental evidence. Neuropathological studies in human brain samples and both in vivo and in vitro models support the hypothesis that nigrostriatal synapses may indeed be affected at the earliest stages of the neurodegenerative process. The mechanisms leading to either structural or functional synaptic dysfunction are starting to be elucidated and include dysregulation of axonal transport, impairment of the exocytosis and endocytosis machinery, altered intracellular trafficking, and loss of corticostriatal synaptic plasticity. The aim of this review is to try to integrate different lines of evidence from both pathogenic and genetic animal models that, to different extents, suggest that early synaptic impairment may represent the key event in PD pathogenesis. Understanding the molecular and cellular events underlying such synaptopathy is a fundamental step toward developing specific biomarkers of early dopaminergic dysfunction and, more importantly, designing novel therapies targeting the synaptic apparatus of selective, vulnerable synapses. (c) 2016 International Parkinson and Movement Disorder Society. PMID- 27193207 TI - Outcomes after resection and/or radiofrequency ablation for recurrence after treatment of colorectal liver metastases. AB - BACKGROUND: Repeat liver resection for colorectal liver metastases (CRLMs) is possible in a limited number of patients, with radiofrequency ablation (RFA) as an alternative for unresectable CRLMs. The aim of this study was to analyse survival rates with these interventions. METHODS: This was a database analysis of patients who underwent first and repeat interventions for synchronous and metachronous CRLMs between 2000 and 2013. Descriptive and survival statistics were calculated. RESULTS: Among 431 patients who underwent resection or RFA for CRLMs, 305 patients developed recurrences for which 160 repeat interventions (resection and/or RFA or ablative radiotherapy) were performed. In total, after 707 first or repeat interventions, 516 recurrences (73.0 per cent) developed, of which 276 were retreated curatively. At the time of first intervention, independent risk factors for death were lymph node-positive primary tumour (hazard ratio (HR) 1.40; P = 0.030), more than one CRLM (HR 1.53; P = 0.007), carcinoembryonic antigen level exceeding 200 ng/ml (HR 1.89; P = 0.020) and size of largest CRLM greater than 5 cm (HR 1.54; P = 0.014). The 5-year overall survival rates for liver resection and percutaneous RFA as first intervention were 51.9 and 53 per cent, with a median overall survival of 65.0 (95 per cent c.i. 47.3 to 82.6) and 62.1 (52.2 to 72.1) months, respectively. CONCLUSION: RFA had good oncological outcomes in patients with unresectable CRLMs. Radiofrequency ablation is progressively more applied with each additional intervention. PMID- 27193206 TI - Reversible decline in pulmonary function during left ventricular assist device therapy. AB - Cardiac replacement therapy, consisting of left ventricular assist device (LVAD) implant surgery and heart transplantation, has considerably reduced the mortality and morbidity of patients with stage D heart failure. However, its impact on pulmonary function remains unclear. We retrospectively evaluated 22 consecutive patients (16 men; 42 +/- 13 years old) who had undergone pulmonary function tests during the heart failure, LVAD, and heart transplantation periods. The LVAD therapy lasted an average of 871 +/- 267 days. The % vital capacity and forced expiratory volume in 1 s decreased significantly after LVAD implantation and returned to baseline levels after heart transplantation. Correlation analysis indicated that a shorter duration of LVAD support was associated with a more significant improvement in % vital capacity in heart transplantation recipients, compared to the pre-LVAD period and the LVAD period. In conclusion, we provide evidence that a decrease in pulmonary function occurs during LVAD support but it may be reversible. Limited LVAD duration may be a key for the recovery of pulmonary dysfunction. PMID- 27193209 TI - Corrigendum for: Accommodating Presuppositions is Inappropriate in Implausible Contexts, by Raj Singh, Evelina Fedorenko, Kyle Mahowald, Edward Gibson in Cognitive Science, 40(3). PMID- 27193208 TI - Is mucin a determinant of peritoneal dissemination of gastrointestinal cancer? Analysis of mucin depletion in two preclinical models. AB - BACKGROUND: Mucinous gastrointestinal cancers may indicate a higher propensity for widespread peritoneal seeding than their non-mucinous counterparts. We hypothesized that mucin content of gastrointestinal cancer cells and tumors is an indicator of cell viability and a determinant of the peritoneal tumor burden and tested our hypothesis in relevant experimental models. METHODS: MKN45 and LS174T models of human gastrointestinal cancer were treated with known mucin-depleting agents in vitro and in vivo, their mucin production was evaluated with Western blot immunohistochemistry, PAS staining and ELISA, and its correlation with cell viability and peritoneal tumor burden was analyzed. RESULTS: A relationship was found between the viability of cancer cells and their mucin levels in vitro. In agreement, when treated animal models were categorized into low- and high-burden groups (based on the weight and number of the peritoneal nodules), tumoral mucin levels were found to be significantly higher in the latter group. CONCLUSIONS: Tumoral mucin is apparently among the factors that dictate the pattern and extent of the peritoneal spread of gastrointestinal cancer, where it allows for enhanced dissemination and redistribution. If further tested and validated, our hypothesis could lay the basis for the development of novel mucin-targeted strategies. PMID- 27193210 TI - Chiral Nanoparticles/Lewis Acids as Cooperative Catalysts for Asymmetric 1,4 Addition of Arylboronic Acids to alpha,beta-Unsaturated Amides. AB - Cooperative catalysts consisting of chiral Rh/Ag nanoparticles and Sc(OTf)3 have been developed that catalyze asymmetric 1,4-addition reactions of arylboronic acids with alpha,beta-unsaturated amides efficiently. The reaction has been considered one of the most challenging reactions because of the low reactivity of the amide substrates. The new catalysts provide the desired products with outstanding enantioselectivities (>98 % ee) in the presence of low loadings (<0.5 mol %) of the catalyst. PMID- 27193211 TI - Selective binding of estrogen receptor alpha to ubiquitin chains. AB - Ubiquitin (Ub)-binding domains (UBDs) noncovalently contact the Ub modification on binding partners. Ub possesses seven lysine (K) residues (i.e., K6, K11, K27, K29, K33, K48, and K63) that can be used to form different chains based on different Ub linkage types (e.g., monoubiquitination/polyubiquitination). Thus, different Ub-based signals exist and are decoded by UBDs. Recently, we have reported the existence of two Ub binding surfaces located within the estrogen receptor alpha (ERalpha) protein. We have shown that the leucine (L) 429 and alanine (A) 430 ERalpha residues direct noncovalent receptor binding to K63-based Ub chains in vitro. However, mutation of L429 and A430 residues did not completely abolish the ability of ERalpha to associate with Ub in cell lines. Thus, we evaluated the possibility that one or both ERalpha Ub binding surfaces could non-covalently interact with other Ub chains. Here, we report that ERalpha selectively binds to specific Ub chains based on different Ub linkages and that ERalpha monoubiquitination requires non-covalent ERalpha:Ub binding. Considering the importance of the UBD:Ub interaction in the initiation and progression of many diseases (e.g., cancer), our data provide novel insights into ERalpha functions that could be relevant to ERalpha-related diseases. (c) 2016 IUBMB Life, 68(7):569-577, 2016. PMID- 27193213 TI - Diversified pulse generation from frequency shifted feedback Tm-doped fibre lasers. AB - Pulsed fibre lasers operating in the eye-safe 2 MUm spectral region have numerous potential applications in areas such as remote sensing, medicine, mid-infrared frequency conversion, and free-space communication. Here, for the first time, we demonstrate versatile 2 MUm ps-ns pulses generation from Tm-based fibre lasers based on frequency shifted feedback and provide a comprehensive report of their special behaviors. The lasers are featured with elegant construction and the unparalleled capacity of generating versatile pulses. The self-starting mode locking is initiated by an intra-cavity acousto-optical frequency shifter. Diversified mode-locked pulse dynamics were observed by altering the pump power, intra-cavity polarization state and cavity structure, including as short as 8 ps single pulse sequence, pulse bundle state and up to 12 nJ, 3 ns nanosecond rectangular pulse. A reflective nonlinear optical loop mirror was introduced to successfully shorten the pulses from 24 ps to 8 ps. Beside the mode-locking operation, flexible Q-switching and Q-switched mode-locking operation can also be readily achieved in the same cavity. Up to 78 MUJ high energy nanosecond pulse can be generated in this regime. Several intriguing pulse dynamics are characterized and discussed. PMID- 27193212 TI - Out-of-hospital cardiac arrest patients treated with cardiopulmonary resuscitation using extracorporeal membrane oxygenation: focus on survival rate and neurologic outcome. AB - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a useful treatment for refractory out-of-hospital cardiac arrest (OHCA). However, little is known about the predictors of survival and neurologic outcome after ECMO. We analyzed our institution's experience with ECMO for refractory OHCA and evaluated the predictors of survival and neurologic outcome after ECMO. METHODS: This was a retrospective review of the medical records of 23 patients who were treated with ECMO due to OHCA that was unresponsive to conventional cardiopulmonary resuscitation, between January 2009 and January 2014. RESULTS: Our ECMO team was activated within 10 min for refractory OHCA, and the 30-day survival rate was 43.5 %. In a multivariate analysis that evaluated independent factors contributing to mortality, urine output <= 0.5 mL . kg(-1) . h(-1) (defined as oliguria) during the 24 h after ECMO was statistically significant (OR, 32.271; 95 % CI, 1.379-755.282; p = 0.031). Just after ECMO implantation, 6 of the 9 patients (66.7 %) who had normal findings on brain computed tomography (CT) survived with a cerebral performance category (CPC) of grade 1. However, only 3 of the 11 patients (27 %) who had evidence of hypoxic brain damage on initial brain CT survived (their CPC grade was 4). CONCLUSIONS: Based on our findings, the survival rate can be improved by rapid implantation of ECMO, and oliguria seen during the first 24 h after ECMO may be an independent predictor of mortality. Furthermore, findings on brain CT just after ECMO and subsequent images may represent an important predictor for neurologic outcome after ECMO. PMID- 27193214 TI - Very High Levels of High-Density Lipoprotein Cholesterol and Cardiovascular Events in Japanese Population. PMID- 27193215 TI - Scleroderma-like skin changes occurring after the use of paclitaxel without any chemical solvents: a first case report. PMID- 27193216 TI - Distribution of Amblydromalus limonicus in northeastern Spain and diversity of phytoseiid mites (Acari: Phytoseiidae) in tomato and other vegetable crops after its introduction. AB - Amblydromalus limonicus (Garman and McGregor) was detected for the first time in 2011 on tomatoes of several locations of the northeastern Spain. During 2012 and 2013 samplings on tomato crop cultivars in the two provinces of Catalonia where the species was found were carried out. The goals of the study were to know the range of spread of the species in these two provinces, its abundance in tomato cultivars, non-crop vegetation among them, in the different parts of the tomato plant and in some other vegetable crops. Results showed that A. limonicus was present at both regions sampled, although there were significant differences in the abundance of the species between sampling points. It is the second in abundance in tomato and the cultivars that most frequently host A. limonicus were Anaidis, Hybrid and Marmande. No significant differences were found in the abundance of A. limonicus among tomato plant canopy strata. On average, it accounted for 31.6 % of all sampled phytoseiids. It was present in four crops (tomato, bean, cucumber and strawberry) and in Amaranthus cruentus, Chenopodium polyspermum, Cynodon dactylon, Mentha sp., Parietaria officinalis and Phleum pratense. Amblydromalus limonicus is well established in the extreme northeast of Spain all year round in crops and non-crops. PMID- 27193217 TI - Reproductive outcomes following preimplantation genetic diagnosis using fluorescence in situ hybridization for 52 translocation carrier couples with a history of recurrent pregnancy loss. AB - Forty-six reciprocal and six Robertsonian translocation carrier couples who experienced recurrent pregnancy loss underwent fluorescence in situ hybridization based preimplantation genetic diagnosis (PGD) for the presence of the two translocated chromosomes. Out of 52 couples, 17 (33%) were undergoing infertility treatment. In total, 239 PGD cycles as oocyte retrieval (OR) were applied. The transferrable rate of negatively diagnosed embryos at the cleavage stage was 26.3%; 71 embryos were transferred as single blastocysts. The clinical pregnancy rate per transfer was 60.6%. We obtained 41 healthy live births with 3 incidences of miscarriage (7.0%). The average cumulative live birth rate was 76.9% during 4.6 OR cycles using a mild ovarian stimulation strategy. The outcomes were classified into four groups based on carrier gender and maternal age (young (<38 years) or advanced). PGD was performed for 52 couples of which the average number of OR cycles was 4.1, 2.1, 6.7 and 4.5 in young female and male carriers and female and male carriers of advanced age; the live birth rate for a primiparity was 77.8, 72.7, 66.7 and 50.0% in those groups. These results suggest that the final live birth rate might be influenced by maternal age regardless of the gender of the carrier. PMID- 27193218 TI - Novel European SLC1A4 variant: infantile spasms and population ancestry analysis. AB - SLC1A4 deficiency is a recently described neurodevelopmental disorder associated with microcephaly, global developmental delay, abnormal myelination, thin corpus callosum and seizures. It has been mainly reported in the Ashkenazi-Jewish population with affected individuals homozygous for the p.Glu256Lys variant. Exome sequencing performed in an Irish proband identified a novel homozygous nonsense SLC1A4 variant [p.Trp453*], confirming a second case of SLC1A4 associated infantile spasms. As this is the first European identified, population ancestry analysis of the Exome Aggregation Consortium database was performed to determine the wider ethnic background of SLC1A4 deficiency carriers. p.Glu256Lys was found in Hispanic and South Asian populations. Other potential disease causing variants were also identified. Investigation for SLC1A4 deficiency should be performed regardless of ethnicity and extend to include unexplained early onset epileptic encephalopathy. PMID- 27193220 TI - EED-associated overgrowth in a second male patient. AB - Following our discovery that constitutional mutations in EED can cause overgrowth, we screened our cohort of patients with Weaver-like features for mutations in this gene. Here we describe a second patient with a different, rare and de novo mutation in EED. Phenotypic overlap with our first case of EED associated overgrowth is significant. Now that we have found two unrelated families of different ethnicities, with a similar rare phenotype, both associated with de novo mutations in this member of the PRC2 complex, we are confident that EED is indeed a novel overgrowth gene. PMID- 27193219 TI - A significant association between rs8067378 at 17q12 and invasive cervical cancer originally identified by a genome-wide association study in Han Chinese is replicated in a Japanese population. AB - In this study, associations between invasive cervical cancer and four cervical cancer susceptibility loci (rs13117307 at 4q12, rs8067378 at 17q12, and rs4282438 and rs9277952 at 6p21.32) in the Han Chinese population were investigated in a Japanese population. Human leukocyte antigen (HLA)-DPB1 alleles were also investigated for their association with cervical cancer risk in the Japanese population. After receiving written informed consent, 214 unrelated Japanese women with invasive cervical cancer and 288 cancer-free Japanese women were recruited, and DNA samples were obtained (study protocol approved by Institutional Review Board of Nagasaki University). Of the four single-nucleotide polymorphisms, rs8067378 showed a significant association with invasive cervical cancer (P=0.0071). Under a recessive model, the minor allele G of rs8067378 contributed to the risk of invasive cervical cancer (odds ratio=2.92, 95% confidence interval=1.40-6.36; P=0.0021). No association was detected between HLA DPB1 alleles and cervical cancer risk in the Japanese population. In conclusion, we show for the first time, to the best of our knowledge, that an association between increased risk of invasive cervical cancer and rs8067378 in the Han Chinese population is replicated in a Japanese population. In addition, Japanese women with the GG genotype of rs8067378 are a candidate high-risk group for invasive cervical carcinoma. PMID- 27193222 TI - Genotyping NUDT15 can predict the dose reduction of 6-MP for children with acute lymphoblastic leukemia especially at a preschool age. AB - The pharmacokinetics among children has been altered dynamically. The difference between children and adults is caused by immaturity in things such as metabolic enzymes and transport proteins. The periods when these alterations happen vary from a few days to some years after birth. We hypothesized that the effect of gene polymorphisms associated with the dose of medicine could be influenced by age. In this study, we analyzed 51 patients with childhood acute lymphoblastic leukemia (ALL) retrospectively. We examined the associations between the polymorphism in NUDT15 and clinical data, especially the dose of 6-mercaptopurine (6-MP). Ten of the patients were heterozygous for the variant allele in NUDT15. In patients under 7 years old with NUDT15 variant allele, the average administered dose of 6-MP was lower than that for the patients homozygous for the wild-type allele (P=0.04). Genotyping of NUDT15 could be a beneficial to estimate the tolerated dose of 6-MP for patients with childhood ALL, especially at a preschool age in Japan. Furthermore, the analysis with stratification by age might be useful in pharmacogenomics among children. PMID- 27193223 TI - Androgen receptor CAG polymorphism and sporadic and early-onset prostate cancer among Mexican men. AB - A short CAG repeat length in the gene encoding for the androgen receptor (AR) has been associated with prostate cancer (PC) risk and aggressiveness. In Latino men, information on this association is scarce. Hence, the aim of this study was to evaluate this association in Mexican males. Using fragment analysis by capillary electrophoresis, we determined the number of CAG repeats-(CAG)n-in AR gene from 158 incident PC cases and 326 age-matched healthy controls (+/-5 years), residing in Mexico City, Mexico. According to Gleason scale and age at diagnosis, cases were classified as high (?7) and low grade (<7), as well as early onset (<60 years) or late onset PC (?60 years). At diagnosis, 78% of cases were classified as high-grade and 26.6% as early onset. Men with sporadic (no family history of PC) and early-onset PC presented shorter CAG repeat length than controls (18.6+/ 2.2 vs 19.5+/-2.5; P=0.02). Lower number of CAG repeats (CAG)?19 were associated with a greater risk for early-onset PC (odds ratio: 2.31; 95% confidence interval: 1.14-4.69). CAG repeat length could increase the risk for sporadic and early-onset PC. The best cutoff point for identifying at-risk subjects was (CAG)19. However, further studies are necessary to replicate our findings in subjects with a family history of PC and also to evaluate the association between CAG repeats length and disease progression. PMID- 27193224 TI - Analysis of phenotype, enzyme activity and genotype of Chinese patients with POMT1 mutation. AB - Protein O-mannosyltransferase 1 (POMT1) is a glycosyltransferase involved in alpha-dystroglycan glycosylation. POMT1 mutations cause a wide spectrum of clinical conditions from Walker-Warburg syndrome (WWS), which involves muscle, eye and brain abnormalities, to mild forms of limb-girdle muscular dystrophy with mental retardation. We aimed to elucidate the impact of different POMT1 mutations on the clinical phenotype. We report five Chinese patients with POMT1 mutations: one had a typical clinical manifestation of WWS, and the other four were diagnosed with congenital muscular dystrophy with mental retardation of varying severity. We analyzed the influence of the POMT1 mutations on POMT activity by assaying the patients' muscles and cultured skin fibroblasts. We demonstrated different levels of decreased POMT activity that correlated highly with decreased alpha-dystroglycan glycosylation. Our results suggest that POMT activity is inversely proportional to clinical severity, and demonstrate that skin fibroblasts can be used for differential diagnosis of patients with alpha dystroglycanopathies. We have provided clinical, histological, enzymatic and genetic evidence of POMT1 involvement in five unrelated Chinese patients. PMID- 27193221 TI - Otopalatodigital spectrum disorders: refinement of the phenotypic and mutational spectrum. AB - Otopalatodigital spectrum disorders (OPDSD) constitute a group of dominant X linked osteochondrodysplasias including four syndromes: otopalatodigital syndromes type 1 and type 2 (OPD1 and OPD2), frontometaphyseal dysplasia, and Melnick-Needles syndrome. These syndromes variably associate specific facial and extremities features, hearing loss, cleft palate, skeletal dysplasia and several malformations, and show important clinical overlap over the different entities. FLNA gain-of-function mutations were identified in these conditions. FLNA encodes filamin A, a scaffolding actin-binding protein. Here, we report phenotypic descriptions and molecular results of FLNA analysis in a large series of 27 probands hypothesized to be affected by OPDSD. We identified 11 different missense mutations in 15 unrelated probands (n=15/27, 56%), of which seven were novel, including one of unknown significance. Segregation analyses within families made possible investigating 20 additional relatives carrying a mutation. This series allows refining the phenotypic and mutational spectrum of FLNA mutations causing OPDSD, and providing suggestions to avoid the overdiagnosis of OPD1. PMID- 27193226 TI - Spectroscopic Evidence for the Two C-H-Cleaving Intermediates of Aspergillus nidulans Isopenicillin N Synthase. AB - The enzyme isopenicillin N synthase (IPNS) installs the beta-lactam and thiazolidine rings of the penicillin core into the linear tripeptide l-delta aminoadipoyl-l-Cys-d-Val (ACV) on the pathways to a number of important antibacterial drugs. A classic set of enzymological and crystallographic studies by Baldwin and co-workers established that this overall four-electron oxidation occurs by a sequence of two oxidative cyclizations, with the beta-lactam ring being installed first and the thiazolidine ring second. Each phase requires cleavage of an aliphatic C-H bond of the substrate: the pro-S-CCys,beta-H bond for closure of the beta-lactam ring, and the CVal,beta-H bond for installation of the thiazolidine ring. IPNS uses a mononuclear non-heme-iron(II) cofactor and dioxygen as cosubstrate to cleave these C-H bonds and direct the ring closures. Despite the intense scrutiny to which the enzyme has been subjected, the identities of the oxidized iron intermediates that cleave the C-H bonds have been addressed only computationally; no experimental insight into their geometric or electronic structures has been reported. In this work, we have employed a combination of transient-state-kinetic and spectroscopic methods, together with the specifically deuterium-labeled substrates, A[d2-C]V and AC[d8-V], to identify both C-H-cleaving intermediates. The results show that they are high-spin Fe(III) superoxo and high-spin Fe(IV)-oxo complexes, respectively, in agreement with published mechanistic proposals derived computationally from Baldwin's founding work. PMID- 27193225 TI - Composition of Rosenthal Fibers, the Protein Aggregate Hallmark of Alexander Disease. AB - Alexander disease (AxD) is a neurodegenerative disorder characterized by astrocytic protein aggregates called Rosenthal fibers (RFs). We used mouse models of AxD to determine the protein composition of RFs to obtain information about disease mechanisms including the hypothesis that sequestration of proteins in RFs contributes to disease. A method was developed for RF enrichment, and analysis of the resulting fraction using isobaric tags for relative and absolute quantitation mass spectrometry identified 77 proteins not previously associated with RFs. Three of five proteins selected for follow-up were confirmed enriched in the RF fraction by immunobloting of both the AxD mouse models and human patients: receptor for activated protein C kinase 1 (RACK1), G1/S-specific cyclin D2, and ATP-dependent RNA helicase DDX3X. Immunohistochemistry validated cyclin D2 as a new RF component, but results for RACK1 and DDX3X were equivocal. None of these was decreased in the non-RF fractions compared to controls. A similar result was obtained for the previously known RF component, alphaB-crystallin, which had been a candidate for sequestration. Thus, no support was obtained for the sequestration hypothesis for AxD. Providing possible insight into disease progression, the association of several of the RF proteins with stress granules suggests a role for stress granules in the origin of RFs. PMID- 27193229 TI - On evolution operators of genetic coalgebras. AB - We characterize evolutionary operators acting on coalgebras with genetic realization modeling the backwards genetic inheritance in Mendelian genetic systems. This characterization is made in terms of the different slices of the cubic stochastic matrix of type (1,2) given by the transition probabilities defining the genetic coalgebra comultiplication. We use the obtained characterization to describe all possible equilibrium states a genetic population can reach when tracing the genetic information one generation back. PMID- 27193227 TI - Biomechanical effects of body weight support with a novel robotic walker for over ground gait rehabilitation. AB - Body weight support (BWS) promotes better functional outcomes for neurologically challenged patients. Despite the established effectiveness of BWS in gait rehabilitation, the findings on biomechanical effects of BWS training still remain contradictory. Therefore, the aim of this study is to comprehensively investigate the effects of BWS. Using a newly developed robotic walker which can facilitate pelvic motions with an active BWS unit, we compared gait parameters of ten healthy subjects during a 10-m walk with incremental levels of body weight unloading, ranging from 0 to 40 % at 10 % intervals. Significant changes in joint angles and gait temporospatial parameters were observed. In addition, the results of an EMG signal study showed that the intensity of muscle activation was significantly reduced with increasing BWS levels. The reduction was found at the ankle, knee, and hip joints in the sagittal plane as well as at the hip joint in the frontal plane. The results of this study provide an important indication of increased lateral body balance and greater stabilization in sagittal and frontal plane during gait. Our findings provide a better understanding of the biomechanical effects of BWS during gait, which will help guide the gait rehabilitation strategies. PMID- 27193228 TI - Effects of slow and regular breathing exercise on cardiopulmonary coupling and blood pressure. AB - Investigation of the interaction between cardiovascular variables and respiration provides a quantitative and noninvasive approach to assess the autonomic control of cardiovascular function. The aim of this paper is to investigate the changes of cardiopulmonary coupling (CPC), blood pressure (BP) and pulse transit time (PTT) during a stepwise-paced breathing (SPB) procedure (spontaneous breathing followed by paced breathing at 14, 12.5, 11, 9.5, 8 and 7 breaths per minute, 3 min each) and gain insights into the characteristics of slow breathing exercises. RR interval, respiration, BP and PTT are collected during the SPB procedure (48 healthy subjects, 27 +/- 6 years). CPC is assessed through investigating both the phase and amplitude dynamics between the respiration-induced components from RR interval and respiration by the approach of ensemble empirical mode decomposition. It was found that even though the phase synchronization and amplitude oscillation of CPC were both enhanced by the SPB procedure, phase coupling does not increase monotonically along with the amplitude oscillation during the whole procedure. Meanwhile, BP was reduced significantly by the SPB procedure (SBP: from 122.0 +/- 13.4 to 114.2 +/- 14.9 mmHg, p < 0.001, DBP: from 82.2 +/- 8.6 to 77.0 +/- 9.8 mmHg, p < 0.001, PTT: from 172.8 +/- 20.1 to 176.8 +/- 19.2 ms, p < 0.001). Our results demonstrate that the SPB procedure can reduce BP and lengthen PTT significantly. Compared with amplitude dynamics, phase dynamics is a different marker for CPC analysis in reflecting cardiorespiratory coherence during slow breathing exercise. Our study provides a methodology to practice slow breathing exercise, including the setting of target breathing rate, change of CPC and the importance of regular breathing. The applications and usability of the study results have also been discussed. PMID- 27193230 TI - Social interactions and children with asthma. AB - This article reviews the literature on the effects of living in a disenfranchised community for low-income African American children who have asthma. The review focuses on social integration, social network, interactions with parents, and limited cultural resources, which lead to negative health outcomes among these children. PMID- 27193234 TI - Isomorphous template induced crystallisation: a robust method for the targeted crystallisation of computationally predicted metastable polymorphs. AB - A new method of inducing the crystallisation of metastable polymorphs by isomorphous templating has been developed and used to reproduce the crystallisation of CBZ-V on the surface of DHC-II. Studies of the growth of CBZ-V on DHC-II single crystals show crystals growing laterally and vertically on DHC II surfaces without any significant face selectivity. The generality of this computationally inspired crystallisation approach is demonstrated by producing the first crystals of an entirely new polymorph of cyheptamide, which is isomorphous to both DHC-II and CBZ-V. PMID- 27193231 TI - Creatine ingestion augments dietary carbohydrate mediated muscle glycogen supercompensation during the initial 24 h of recovery following prolonged exhaustive exercise in humans. AB - Muscle glycogen availability can limit endurance exercise performance. We previously demonstrated 5 days of creatine (Cr) and carbohydrate (CHO) ingestion augmented post-exercise muscle glycogen storage compared to CHO feeding alone in healthy volunteers. Here, we aimed to characterise the time-course of this Cr induced response under more stringent and controlled experimental conditions and identify potential mechanisms underpinning this phenomenon. Fourteen healthy, male volunteers cycled to exhaustion at 70 % VO2peak. Muscle biopsies were obtained at rest immediately post-exercise and after 1, 3 and 6 days of recovery, during which Cr or placebo supplements (20 g day(-1)) were ingested along with a prescribed high CHO diet (37.5 kcal kg body mass(-1) day(-1), >80 % calories CHO). Oral-glucose tolerance tests (oral-GTT) were performed pre-exercise and after 1, 3 and 6 days of Cr and placebo supplementation. Exercise depleted muscle glycogen content to the same extent in both treatment groups. Creatine supplementation increased muscle total-Cr, free-Cr and phosphocreatine (PCr) content above placebo following 1, 3 and 6 days of supplementation (all P < 0.05). Creatine supplementation also increased muscle glycogen content noticeably above placebo after 1 day of supplementation (P < 0.05), which was sustained thereafter. This study confirmed dietary Cr augments post-exercise muscle glycogen super-compensation, and demonstrates this occurred during the initial 24 h of post-exercise recovery (when muscle total-Cr had increased by <10 %). This marked response ensued without apparent treatment differences in muscle insulin sensitivity (oral-GTT, muscle GLUT4 mRNA), osmotic stress (muscle c-fos and HSP72 mRNA) or muscle cell volume (muscle water content) responses, such that another mechanism must be causative. PMID- 27193232 TI - Identification of hydrophobic interactions between relaxin-3 and its receptor RXFP3: implication for a conformational change in the B-chain C-terminus during receptor binding. AB - Relaxin-3 is an insulin/relaxin superfamily neuropeptide implicated in the regulation of food intake and stress response via activation of the G protein coupled receptor RXFP3. Their electrostatic interactions have been recently identified, and involves three positively charged B-chain residues (B12Arg, B16Arg, and B26Arg) of relaxin-3 and two negatively charged residues (Glu141 and Asp145) in a highly conserved ExxxD motif at the extracellular end of the second transmembrane domain of RXFP3. To investigate their hydrophobic interactions, in the present work we deleted the highly conserved B-chain C-terminal B27Trp residue of relaxin-3, and mutated four highly conserved aromatic residues (Phe137, Trp138, Phe146, and Trp148) around the ExxxD motif of RXFP3. The resultant [?B27W]relaxin-3 exhibited approximately tenfold lower binding potency and ~1000-fold lower activation potency towards wild-type RXFP3, confirming its importance for relaxin-3 function. Although the RXFP3 mutants could be normally trafficked to cell membrane, they had quite different activities. [F137A]RXFP3 could normally distinguish wild-type relaxin-3 and [?B27W]relaxin-3 in binding and activation assays, whereas [W138A]RXFP3 lost most of this capability, suggesting that the Trp138 residue of RXFP3 forms hydrophobic interactions with the B27Trp residue of relaxin-3. The hydrophobic Trp138 residue and the formerly identified negatively charged Glu141 and Asp145 residues in the highly conserved WxxExxxD motif may thus form a functional surface that is important for interaction with relaxin-3. We hypothesize that the relaxin-3 B-chain C-terminus changes from the original folding-back conformation to an extended conformation during binding with RXFP3, to allow its B27Trp and B26Arg residues to interact with the Trp138 and Glu141 residues of RXFP3, respectively. PMID- 27193233 TI - Destabilization of the ornithine decarboxylase mRNA transcript by the RNA-binding protein tristetraprolin. AB - Ornithine decarboxylase (ODC) is the first and usually rate-limiting enzyme in the polyamine biosynthetic pathway. In a normal physiological state, ODC is tightly regulated. However, during neoplastic transformation, ODC expression becomes upregulated. The studies described here show that the ODC mRNA transcript is destabilized by the RNA-binding protein tristetraprolin (TTP). We show that TTP is able to bind to the ODC mRNA transcript in both non-transformed RIE-1 cells and transformed Ras12V cells. Moreover, using mouse embryonic fibroblast cell lines that are devoid of a functional TTP protein, we demonstrate that in the absence of TTP both ODC mRNA stability and ODC enzyme activity increase when compared to wild-type cells. Finally, we show that the ODC 3' untranslated region contains cis acting destabilizing elements that are affected by, but not solely dependent on, TTP expression. Together, these data support the hypothesis that TTP plays a role in the post-transcriptional regulation of the ODC mRNA transcript. PMID- 27193235 TI - [The Interdisciplinary Conference on Lacrimal System Disorders of ophthalmic and ENT surgeons at the University Hospital Halle : An analysis of present patient material]. AB - BACKGROUND AND AIM: The lacrimal system (LS) crosses regions of ocular adnexa, the nose, and the paranasal sinuses. Surgery of disorders requires a targeted ophthalmologic and otolaryngologic examination. Since 2013, an Interdisciplinary Conference on Lacrimal System Disorders (ICLSD) has existed at the University Hospital Halle. First results of our experiences with this cooperation between ophthalmic and ENT surgeons are presented. METHODS: In a retrospective study at the Department of Ophthalmology, University Hospital Halle, all patients aged 22 80 years (n = 43, 10 with bilateral manifestation; mean age 65.1 years) having had a consultation in ICLSD between February 2013 and May 2015 were analyzed. Thereby, 53 LS were included in the descriptive evaluation. RESULTS: The main relevant pathology in terms of ophthalmologic manifestation was chronic dacryocystitis and its complications (n = 42), whereas nasal septum deviation (n = 11) and chronic rhinosinusitis (n = 10) were the most frequent otorhinolaryngologic pathologies. Prior to consultation, ENT (n = 34) and/or ophthalmic surgery (n = 40) had been performed. During ICLSD, an individualized therapeutic regime for each patient was developed. Surgery was required in 43 out of 53 LS. Of these, 32 were mainly ophthalmic, 11 mainly ENT interventions. At the time of evaluation (median 3 months; range 1 to 24 months), 29 out of 38 patients (76.3 %) were free of complaints. CONCLUSION: Since 2013, competences of ophthalmic and ENT surgeons have been integrated in ICLSD for advanced diagnosis and therapy of lacrimal disorders at the University Hospital Halle. Encouraging functional results are shown in this study, as most patients have had a long and complicated history of lacrimal system disorders. ICLSD enables interdisciplinary patient care. PMID- 27193237 TI - Boosting Responsivity of Organic-Metal Oxynitride Hybrid Heterointerface Phototransistor. AB - Amorphous metal oxides are attractive materials for various sensor applications, because of high electrical performance and easy processing. However, low absorption coefficient, slow photoresponse, and persistent photoconductivity of amorphous metal oxide films from the origin of deep-level defects are obstacles to their use as photonic applications. Here, we demonstrate ultrahigh photoresponsivity of organic-inorganic hybrid phototransistors featuring bulk heterojunction polymers and low-bandgap zinc oxynitride. Spontaneous formation of ultrathin zinc oxide on the surface of zinc oxynitride films could make an effective band-alignment for electron transfer from the dissociation of excitons in the bulk heterojunction, while holes were blocked by the deep highest occupied molecular orbital level of zinc oxide. These hybrid structure-based phototransistors are ultrasensitive to broad-bandwidth photons in ultraviolet to near-infrared regions. The detectivity and a linear dynamic range exceeded 10(12) Jones and 122.3 dB, respectively. PMID- 27193239 TI - Induction and Tunability of Self-Healing Property of Dendron Based Hydrogel Using Clay Nanocomposite. AB - Low molecular weight gels have relatively poor self-healing capacity compared to that of polymeric gels. Induction and tuning of the healing capacity of low molecular weight gels to achieve desired applications are thus challenging tasks. The present work describes the achievement of remarkable tunability of self healing property for a low molecular weight hybrid gel, based on poly(aryl ether) dendron derivative (PAD). The hybrid gel has been synthesized using PAD and poly(amido amine) {PAMAM} dendrimer derivative (QPD), which are intercalated in the montmorillonite clay (MMT) layers. The self-healing of the hybrid gel (QPD MMT-PAD) was demonstrated through experiments where the distorted gel regained the initial value of storage modulus (G') within a few minutes. Further, the propensity of self-healing of the gel has been tuned as a function of QPD concentration. The mechanically stable QPD-MMT-PAD hybrid gel has been utilized for the adsorption of ppm level concentration of polycyclic aromatic hydrocarbons (PAHs) such as beta-naphthol, pyrene, and phenenathrene from water with excellent efficiency (80-98%). PMID- 27193238 TI - Effects of Enterococcus faecalis CECT 7121 on Cryptosporidium parvum infection in mice. AB - Cryptosporidium is an opportunistic protozoan parasite of humans and animals worldwide and causes diarrheal disease that is typically self-limiting in immunocompetent hosts but often life threatening to immunocompromised individuals. However, there is a lack of completely efficient therapy available. Probiotics have attracted the attention as potential antiparasite compounds against protozoa involved in intestinal infections. This study investigated the effects of administration of probiotic Enterococcus faecalis CECT 7121 on Cryptosporidium parvum infection in immunosuppressed mice. Effects on C. parvum infection at the intestinal mucosa were studied and scored at each portion of the gut. It was demonstrated that Ef CECT 7121 interfered with C. parvum infection when both probiotic and parasite were present in the same intestinal location suggesting that Ef CECT 7121 supplementation can alleviate the negative effects of C. parvum infection. PMID- 27193236 TI - A curated and standardized adverse drug event resource to accelerate drug safety research. AB - Identification of adverse drug reactions (ADRs) during the post-marketing phase is one of the most important goals of drug safety surveillance. Spontaneous reporting systems (SRS) data, which are the mainstay of traditional drug safety surveillance, are used for hypothesis generation and to validate the newer approaches. The publicly available US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) data requires substantial curation before they can be used appropriately, and applying different strategies for data cleaning and normalization can have material impact on analysis results. We provide a curated and standardized version of FAERS removing duplicate case records, applying standardized vocabularies with drug names mapped to RxNorm concepts and outcomes mapped to SNOMED-CT concepts, and pre-computed summary statistics about drug outcome relationships for general consumption. This publicly available resource, along with the source code, will accelerate drug safety research by reducing the amount of time spent performing data management on the source FAERS reports, improving the quality of the underlying data, and enabling standardized analyses using common vocabularies. PMID- 27193240 TI - Egg white/poly (vinyl alcohol)/MMT nanocomposite hydrogels for wound dressing. AB - Nanocomposite hydrogels on the basis of egg white and poly (vinyl alcohol) (PVA) containing 0, 5, and 10 wt.% of montmorillonite (MMT) nanoclay were prepared by a facile cyclic freezing-thawing technique and their properties investigated for wound dressing application. The morphological, structural, thermal, physical, and in vitro cytotoxic properties of the prepared nanocomposite hydrogel wound dressings (NHWDs) were experimentally studied. The NHWDs had an exfoliated morphology with a porous structure having pores sizes in the nanometric scale. It was shown that MMT acted as cross-linker in the network of NHWDs and improved their thermal stabilities. The prepared wound dressings were transparent and their equilibrium water contents and water vapor transmission rates, as two important factors of wound dressings, were very close to the properties of human skin which means that the prepared wound dressings could interact appropriately with the damaged tissues of wounds and protect them like an artificial skin during the wound healing process. The in vitro cytotoxicity assay also confirmed the non-cytotoxic nature of the prepared NHWDs. It was finally concluded that the prepared egg white/PVA/MMT nanocomposite hydrogels are promising materials to be used as novel wound dressings in wound and burn care. PMID- 27193241 TI - Exclusion performance and learning by exclusion in dogs. AB - Responding by exclusion is a type of emergent repertoire in which an individual chooses an alternative by the apparent exclusion of other available alternatives. In this case it is possible to respond appropriately to an undefined stimulus (one that has not previously acquired discriminative functions) by excluding the defined alternatives. There is evidence of exclusion in humans and nonhuman animals, although learning as an outcome of exclusion does not always occur. This study aimed to investigate exclusion in visual simple discriminations and learning of new simple discriminations resulting from exclusion in four border collies. Subjects were trained to perform simple simultaneous discriminations between pairs of tridimensional objects, and were then tested for exclusion, novelty control and learning of new simple discriminations. All dogs successfully responded by exclusion, choosing an undefined stimulus displayed with an S-. For three dogs, it was possible to conclude that these previously undefined stimuli acquired S+ functions, documenting learning of new simple discriminations. However, this required up to four exposures to exclusion trials with each pair of stimuli. PMID- 27193243 TI - Assessing the role of alternative response rates and reinforcer rates in resistance to extinction of target responding when combining stimuli. AB - Studies of behavioral momentum reveal that reinforcing an alternative response in the presence of a target response reduces the rate of target responding but increases its persistence, relative to training the target response on its own. Because of the parallels between these studies and differential-reinforcement techniques to reduce problem behavior in clinical settings, alternative techniques to reduce problem behavior without enhancing its persistence are being explored. One potential solution is to train an alternative response in a separate stimulus context from problem behavior before combining the alternative stimulus with the target stimulus. The present study assessed how differences in reinforcement contingencies and rate for alternative responding influenced resistance to extinction of target responding when combining alternative and target stimuli in pigeons. Across three experiments, alternative stimuli signaling a response-reinforcer dependency and greater reinforcer rates more effectively decreased the persistence of target responding when combining alternative and target stimuli within the same extinction tests, but not when compared across separate extinction tests. Overall, these findings reveal that differences in competition between alternative and target responding produced by contingencies of alternative reinforcement could influence the effectiveness of treating problem behavior through combining stimulus contexts. PMID- 27193242 TI - Behavioral momentum theory fails to account for the effects of reinforcement rate on resurgence. AB - The behavioral-momentum model of resurgence predicts reinforcer rates within a resurgence preparation should have three effects on target behavior. First, higher reinforcer rates in baseline (Phase 1) produce more persistent target behavior during extinction plus alternative reinforcement. Second, higher rate alternative reinforcement during Phase 2 generates greater disruption of target responding during extinction. Finally, higher rates of either reinforcement source should produce greater responding when alternative reinforcement is suspended in Phase 3. Recent empirical reports have produced mixed results in terms of these predictions. Thus, the present experiment further examined reinforcer-rate effects on persistence and resurgence. Rats pressed target levers for high-rate or low-rate variable-interval food during Phase 1. In Phase 2, target-lever pressing was extinguished, an alternative nose-poke became available, and nose-poking produced either high-rate variable-interval, low-rate variable-interval, or no (an extinction control) alternative reinforcement. Alternative reinforcement was suspended in Phase 3. For groups that received no alternative reinforcement, target-lever pressing was less persistent following high-rate than low-rate Phase-1 reinforcement. Target behavior was more persistent with low-rate alternative reinforcement than with high-rate alternative reinforcement or extinction alone. Finally, no differences in Phase-3 responding were observed for groups that received either high-rate or low-rate alternative reinforcement, and resurgence occurred only following high-rate alternative reinforcement. These findings are inconsistent with the momentum based model of resurgence. We conclude this model mischaracterizes the effects of reinforcer rates on persistence and resurgence of operant behavior. PMID- 27193244 TI - A survey of residual analysis and a new test of residual trend. AB - A survey of residual analysis in behavior-analytic research reveals that existing methods are problematic in one way or another. A new test for residual trends is proposed that avoids the problematic features of the existing methods. It entails fitting cubic polynomials to sets of residuals and comparing their effect sizes to those that would be expected if the sets of residuals were random. To this end, sampling distributions of effect sizes for fits of a cubic polynomial to random data were obtained by generating sets of random standardized residuals of various sizes, n. A cubic polynomial was then fitted to each set of residuals and its effect size was calculated. This yielded a sampling distribution of effect sizes for each n. To test for a residual trend in experimental data, the median effect size of cubic-polynomial fits to sets of experimental residuals can be compared to the median of the corresponding sampling distribution of effect sizes for random residuals using a sign test. An example from the literature, which entailed comparing mathematical and computational models of continuous choice, is used to illustrate the utility of the test. PMID- 27193247 TI - Corrigendum to "Comparison of non-HDL-cholesterol versus triglycerides-to HDLcholesterol ratio in relation to cardiometabolic risk factors and preclinical organ damage in overweight/obese children: The CARITALY study" [Nutr Metab Cardiovasc Dis 25 (2015) 489-494]. PMID- 27193248 TI - Can Previewing Sport-Specific Video Influence Reactive-Agility Response Time? AB - The purpose of this study was to examine whether a video-based warm-up could provide an acute performance benefit to response time for athletes in a sport specific agility task. In addition, 2 learning strategies, explicit and implicit, were compared for their effectiveness in facilitating an improvement in sport specific agility. Thirty representative male junior rugby union players (age 14 16 y, mean age 14.6 +/- 1.09 y) were placed in 3 experimental groups (explicit, implicit, and control) and completed 2 intervention sessions. Testing sessions included preintervention testing, completion of the video-based warm-up intervention, and postintervention testing. A 3D motion-analysis system was used to assess response time in the testing battery. The athletes' response times on the pre- to postintervention tests were compared to determine the effectiveness of the video-based warm-up. A 2-way general linear model with repeated-measures analysis indicated that both the explicit (P = .030, d = 0.28) and implicit (P = .049, d = 0.33) groups significantly improved their response time by the intervention compared with the control group (P = .367, d = 0.08). The mean postintervention response time for the explicit group improved by 19.1% (from 0.246 s pre to 0.199 s post), and the implicit group improved by 15.7% (from 0.268 s to 0.226 s). Findings suggest that a video-based warm-up may provide an acute benefit to sport-specific agility performance for junior athletes. PMID- 27193250 TI - Illumina MiSeq sequencing disfavours a sequence motif in the GFP reporter gene. AB - Green fluorescent protein (GFP) is one of the most used reporter genes. We have used next-generation sequencing (NGS) to analyse the genetic diversity of a recombinant influenza A virus that expresses GFP and found a remarkable coverage dip in the GFP coding sequence. This coverage dip was present when virus-derived RT-PCR product or the parental plasmid DNA was used as starting material for NGS and regardless of whether Nextera XT transposase or Covaris shearing was used for DNA fragmentation. Therefore, the sequence coverage dip in the GFP coding sequence was not the result of emerging GFP mutant viruses or a bias introduced by Nextera XT fragmentation. Instead, we found that the Illumina MiSeq sequencing method disfavours the 'CCCGCC' motif in the GFP coding sequence. PMID- 27193251 TI - Fertility preservation option in young women with ovarian cancer. PMID- 27193252 TI - Erratum to: Vitamin D deficiency in patients with either rheumatic diseases or inflammatory bowel diseases on biologic therapy. PMID- 27193254 TI - The Role of DeltaFosB on the Pro-survival Effect of PTHrP in Goat Mammary Epithelial Cells. AB - The mechanism of regulation mammary epithelial cell number in ruminant is not fully understood, but is thought to be dependent on the balance of cell proliferation and cell apoptosis. Parathyroid hormone-related protein (PTHrP) could express in mammary epithelial cells and breast cancer cells, and has been reported to regulate cell survival. Here, we showed that PTHrP induced cell proliferation and increased the expression of CyclinD1 and proliferating cell nuclear antigen (PCNA) in goat mammary epithelial cells (GMEC). PTHrP increased the mRNA levels of anti-apoptosis genes Bcl-2 and Bcl-xl, and protected GMEC from apoptosis. We also found DeltaFosB, an alternative splicing of finkel-biskis jinkins murine osteosarcoma B (fosB), inhibited GMEC apoptosis, and induced cell proliferation with increased Bcl-2/Bax and Bcl-xl/Bax ratios. Interestingly, DeltaFosB could further promote the pro-survival effect of PTHrP, and the Bcl 2/Bax and Bcl-xl/Bax ratios showed higher levels. We conclude that the pro survival role of PTHrP in GMEC may be regulated by DeltaFosB. PMID- 27193255 TI - Loops Adjacent to Catalytic Region and Molecular Stability of Man1312. AB - Hemicelluloses are the second major polysaccharides in nature and can be converted to ethanol product by a variety of enzymes including mannanases. Mannanase is an important enzyme that hydrolyses mannose-containing polysaccharides which are abundant in plants. An optimized mannanase could help to improve conversion process and make the technology efficiently and competitively. In this work, the effects of loops adjacent to active region on enzymic properties of Man1312 were investigated. Loop 6 and 10 are two loops neighboring to Man1312 catalytic region, and deletion mutagenesis and residue substitution were performed on both loops. Deletion on sites S145, Q148, N244, and S255 and substitution on sites N146, S147, S156, and T157 gave significant increased stability to enzyme. The quadruplet mutant ManD4I4 combined all the mutations and had higher optimal temperature and T m value by 5 and 4 degrees C than Man1312, respectively. From our data, we are able to conclude the loops of enzymes are important to design mutagenesis and obtain improved properties, especially the loops neighboring to catalytic region from tertiary structure. In our experiment, residue deletion and substitution on loops neighboring to catalytic region made significant improvement on enzyme properties. PMID- 27193249 TI - Ribosome-based quality control of mRNA and nascent peptides. AB - Quality control processes are widespread and play essential roles in detecting defective molecules and removing them in order to maintain organismal fitness. Aberrant messenger RNA (mRNA) molecules, unless properly managed, pose a significant hurdle to cellular proteostasis. Often mRNAs harbor premature stop codons, possess structures that present a block to the translational machinery, or lack stop codons entirely. In eukaryotes, the three cytoplasmic mRNA surveillance processes, nonsense-mediated decay (NMD), no-go decay (NGD), and nonstop decay (NSD), evolved to cope with these aberrant mRNAs, respectively. Nonstop mRNAs and mRNAs that inhibit translation elongation are especially problematic as they sequester valuable ribosomes from the translating ribosome pool. As a result, in addition to RNA degradation, NSD and NGD are intimately coupled to ribosome rescue in all domains of life. Furthermore, protein products produced from all three classes of defective mRNAs are more likely to malfunction. It is not surprising then that these truncated nascent protein products are subject to degradation. Over the past few years, many studies have begun to document a central role for the ribosome in initiating the RNA and protein quality control processes. The ribosome appears to be responsible for recognizing the target mRNAs as well as for recruiting the factors required to carry out the processes of ribosome rescue and nascent protein decay. WIREs RNA 2017, 8:e1366. doi: 10.1002/wrna.1366 For further resources related to this article, please visit the WIREs website. PMID- 27193256 TI - A Multivariate Approach to Evaluate Biomass Production, Biochemical Composition and Stress Compounds of Spirulina platensis Cultivated in Wastewater. AB - The study was performed to investigate the effects of using cow effluent for the cultivation of Spirulina platensis on its biomass production and cell physiology. S. platensis was cultivated in three different cow effluents (CE) used as cultivation medium during 15 days. CE was prepared using dry cow manures, and it was further modified with supplement of NaNO3 (CEN) and NaNO3 + NaCl (CENS). High nitrate value stimulated chlorophyll-a and total protein content of the cyanobacterium and also biomass production in standards medium (SM) and CEN media. Total carbohydrate content of S. platensis grown in CE media was found to be higher (p < 0.05) than that of SM. Productions of biomass and biochemical compounds by the cyanobacterium grown on the CE and SM media were evaluated by using multivariate approach. Conductivity, oxidation reduction potential (ORP), salinity, pH, and TDS played important role (p < 0.01) in the biochemical composition. As an effective explanatory factor, ORP had a significant positive correlation with H2O2, whereas negatively correlated with chlorophyll-alpha, biomass production, filament length, and proline. Canonical correspondence analysis proposed that biochemical compounds of S. platensis were not only affected by salinity and nutrition of media but also by pH and ORP. The present study indicated that CEN as a low cost model medium had high potential for the production of biomass by S. platensis with high protein content. PMID- 27193257 TI - Tungsten Oxide Nanoplates; the Novelty in Targeting Metalloproteinase-7 Gene in Both Cervix and Colon Cancer Cells. AB - In this study, we synthesized tungsten oxide (WO3) nanoplates, both crystallographic phases and the morphology of the samples were determined by powder x-ray diffraction and the scanning electron microscopy, respectively. The obtained data clarified that, the all prepared WO3.H2O samples were composed of large quantity of nanoplates. The cytotoxicity patterns of nanoplates were checked on both normal and cancer mammalian cell lines. Both nanoplates cytotoxicity did not exceed the 50 % inhibitory concentration (IC50) on the all normal tested cells even by using concentrations up to 1 mg/ml. In addition, orthorhombic tungsten oxide nanoplate was more potent against both Caco2 and Hela cells by showing inhibition percentages in cellular viability 64.749 and 72.27, respectively, and with cancer selectivity index reached 3.2 and 2.6 on both colon and cervix cancer, respectively. The anticancer effects of nanoplates were translated to alteration in both pro-apoptotic and anti-apoptotic genes expressions. Tungsten oxide nanoplates down regulated the expression of B cell lymphoma 2 (Bcl-2) and metalloproteinase-7 (MMP7) genes. In addition, orthorhombic tungsten oxide nanoplates showed more potentiation in IL2 and IL8 induction (40.43 pg/ml) and upregulation of TNF-alpha gene expression but with lower folds than Escherichia coli lipopolysaccharide (LPS) induction. PMID- 27193258 TI - Cell-Cell Communication Between Fibroblast and 3T3-L1 Cells Under Co-culturing in Oxidative Stress Condition Induced by H2O2. AB - The present study was carried out to understand the interaction between fibroblast and 3T3-L1 preadipocyte cells under H2O2-induced oxidative stress condition. H2O2 (40 MUM) was added in co-culture and monoculture of fibroblast and 3T3-L1 cell. The cells in the lower well were harvested for analysis and the process was carried out for both cells. The cell growth, oxidative stress markers, and antioxidant enzymes were analyzed. Additionally, the mRNA expressions of caspase-3 and caspase-7 were selected for analysis of apoptotic pathways and TNF-alpha and NF-kappaB were analyzed for inflammatory pathways. The adipogenic marker such as adiponectin and PPAR-gamma and collagen synthesis markers such as LOX and BMP-1 were analyzed in the co-culture of fibroblast and 3T3-L1 cells. Cell viability and antioxidant enzymes were significantly increased in the co-culture compared to the monoculture under stress condition. The apoptotic, inflammatory, adipogenic, and collagen-synthesized markers were significantly altered in H2O2-induced co-culture of fibroblast and 3T3-L1 cells when compared with the monoculture of H2O2-induced fibroblast and 3T3-L1 cells. In addition, the confocal microscopical investigation indicated that the co culture of H2O2-induced 3T3-L1 and fibroblast cells increases collagen type I and type III expression. From our results, we suggested that co-culture of fat cell (3T3-L1) and fibroblast cells may influence/regulate each other and made the cells able to withstand against oxidative stress and aging. It is conceivable that the same mechanism might have been occurring from cell to cell while animals are stressed by various environmental conditions. PMID- 27193259 TI - Effectiveness and outcomes of a nurse practitioner-run chest pain evaluation unit. AB - BACKGROUND: Every year, more than 5 million patients seek medical care for chest pain. OBJECTIVE: The goal of this study was to evaluate test utilization and outcomes of a nurse practitioner (NP)-based chest pain unit and compare results to data previously reported from our institution. DESIGN, SETTING, AND PARTICIPANTS: The records from 814 consecutive patients with chest pain admitted to the NP-run unit were compared to the outcomes of 250 patients admitted to a separate hospitalist-run unit at a New York City hospital. RESULTS: Forty-four percent of patients in the NP unit underwent stress myocardial perfusion imaging (MPI) as the primary diagnostic test (compared to 22% in the hospitalist unit, p < .0001). The average length of stay was shorter for patients in the NP unit (2.7 +/- 3.6 days compared to 3.9 +/- 3.4 days, p < .0001). Additionally, the 90-day readmission rate was less for patients in the NP unit (2.7% vs. 3.9%, p < .0006). CONCLUSIONS: An NP-run chest pain unit resulted in decreased length of stay and reduced readmission rates compared to a hospitalist-based unit. PMID- 27193260 TI - Enhanced power factor via the control of structural phase transition in SnSe. AB - Tin selenide has attracted much research interest due to its unprecedentedly high thermoelectric figure of merit (ZT). For real applications, it is desirable to increase the ZT value in the lower-temperature range, as the peak ZT value currently exists near the melting point. It is shown in this paper that the structural phase transition plays an important role in boosting the ZT value of SnSe in the lower-temperature range, as the Cmcm phase is found to have a much higher power factor than the Pnma phase. Furthermore, hydrostatic pressure is predicted to be extremely effective in tuning the phase transition temperature based on ab-initio molecular dynamic simulations; a remarkable decrease in the phase transition temperature is found when a hydrostatic pressure is applied. Dynamical stabilities are investigated based on phonon calculations, providing deeper insight into the pressure effects. Accurate band structures are obtained using the modified Becke-Johnson correction, allowing reliable prediction of the electrical transport properties. The effects of hydrostatic pressure on the thermal transport properties are also discussed. Hydrostatic pressure is shown to be efficient in manipulating the transport properties via the control of phase transition temperature in SnSe, paving a new path for enhancing its thermoelectric efficiency. PMID- 27193262 TI - Multiplexed data independent acquisition (MSX-DIA) applied by high resolution mass spectrometry improves quantification quality for the analysis of histone peptides. AB - We present the MS-based application of the innovative, although scarcely exploited, multiplexed data-independent acquisition (MSX-DIA) for the analysis of histone PTMs. Histones are golden standard for complexity in MS based proteomics, due to their large number of combinatorial modifications, leading to isobaric peptides after proteolytic digestion. DIA has, thus, gained popularity for the purpose as it allows for MS/MS-based quantification without upfront assay development. In this work, we evaluated the performance of traditional DIA versus MSX-DIA in terms of MS/MS spectra quality, instrument scan rate and quantification precision using histones from HeLa cells. We used an MS/MS isolation window of 10 and 6 m/z for DIA and MSX-DIA, respectively. Four MS/MS scans were multiplexed for MSX-DIA. Despite MSX-DIA was programmed to perform two fold more MS/MS events than traditional DIA, it acquired on average ~5% more full MS scans, indicating even faster scan rate. Results highlighted an overall decrease of background ion signals using MSX-DIA, and we illustrated specific examples where peptides of different precursor masses were co-fragmented by DIA but not MSX-DIA. Taken together, MSX-DIA proved thus to be a more favorable method for histone analysis in data independent mode. PMID- 27193261 TI - T-bet is a key modulator of IL-23-driven pathogenic CD4(+) T cell responses in the intestine. AB - IL-23 is a key driver of pathogenic Th17 cell responses. It has been suggested that the transcription factor T-bet is required to facilitate IL-23-driven pathogenic effector functions; however, the precise role of T-bet in intestinal T cell responses remains elusive. Here, we show that T-bet expression by T cells is not required for the induction of colitis or the differentiation of pathogenic Th17 cells but modifies qualitative features of the IL-23-driven colitogenic response by negatively regulating IL-23R expression. Consequently, absence of T bet leads to unrestrained Th17 cell differentiation and activation characterized by high amounts of IL-17A and IL-22. The combined increase in IL-17A/IL-22 results in enhanced epithelial cell activation and inhibition of either IL-17A or IL-22 leads to disease amelioration. Our study identifies T-bet as a key modulator of IL-23-driven colitogenic responses in the intestine and has important implications for understanding of heterogeneity among inflammatory bowel disease patients. PMID- 27193263 TI - Merging scleractinian genera: the overwhelming genetic similarity between solitary Desmophyllum and colonial Lophelia. AB - BACKGROUND: In recent years, several types of molecular markers and new microscale skeletal characters have shown potential as powerful tools for phylogenetic reconstructions and higher-level taxonomy of scleractinian corals. Nonetheless, discrimination of closely related taxa is still highly controversial in scleractinian coral research. Here we used newly sequenced complete mitochondrial genomes and 30 microsatellites to define the genetic divergence between two closely related azooxanthellate taxa of the family Caryophylliidae: solitary Desmophyllum dianthus and colonial Lophelia pertusa. RESULTS: In the mitochondrial control region, an astonishing 99.8 % of nucleotides between L. pertusa and D. dianthus were identical. Variability of the mitochondrial genomes of the two species is represented by only 12 non-synonymous out of 19 total nucleotide substitutions. Microsatellite sequence (37 loci) analysis of L. pertusa and D. dianthus showed genetic similarity is about 97 %. Our results also indicated that L. pertusa and D. dianthus show high skeletal plasticity in corallum shape and similarity in skeletal ontogeny, micromorphological (septal and wall granulations) and microstructural characters (arrangement of rapid accretion deposits, thickening deposits). CONCLUSIONS: Molecularly and morphologically, the solitary Desmophyllum and the dendroid Lophelia appear to be significantly more similar to each other than other unambiguous coral genera analysed to date. This consequently leads to ascribe both taxa under the generic name Desmophyllum (priority by date of publication). Findings of this study demonstrate that coloniality may not be a robust taxonomic character in scleractinian corals. PMID- 27193264 TI - Using health and demographic surveillance for the early detection of cholera outbreaks: analysis of community- and hospital-based data from Matlab, Bangladesh. AB - BACKGROUND: Cholera outbreaks are a continuing problem in Bangladesh, and the timely detection of an outbreak is important for reducing morbidity and mortality. In Matlab, the ongoing Health and Demographic Surveillance System (HDSS) data records symptoms of diarrhea in children under the age of 5 years at the community level. Cholera surveillance in Matlab currently uses hospital-based data. OBJECTIVE: The objective of this study is to determine whether increases in cholera in Matlab can be detected earlier by using HDSS diarrhea symptom data in a syndromic surveillance analysis, when compared to hospital admissions for cholera. METHODS: HDSS diarrhea symptom data and hospital admissions for cholera in children under 5 years of age over a 2-year period were analyzed with the syndromic surveillance statistical program EARS (Early Aberration Reporting System). Dates when significant increases in either symptoms or cholera cases occurred were compared to one another. RESULTS: The analysis revealed that there were 43 days over 16 months when the cholera cases or diarrhea symptoms increased significantly. There were 8 months when both data sets detected days with significant increases. In 5 of the 8 months, increases in diarrheal symptoms occurred before increases of cholera cases. The increases in symptoms occurred between 1 and 15 days before the increases in cholera cases. CONCLUSIONS: The results suggest that the HDSS survey data may be able to detect an increase in cholera before an increase in hospital admissions is seen. However, there was no direct link between diarrheal symptom increases and cholera cases, and this, as well as other methodological weaknesses, should be taken into consideration. PMID- 27193265 TI - Post-disaster health impact of natural hazards in the Philippines in 2013. AB - BACKGROUND: In 2011, the Health Emergency Management Bureau (HEMB) created the Surveillance for Post Extreme Emergencies and Disasters (SPEED), a real-time syndromic surveillance system that allows the early detection and monitoring of post-disaster disease trends. SPEED can assist health leaders in making informed decisions on health systems affected by disasters. There is a need for further validation of current concepts in post-disaster disease patterns in respect to actual field data. This study aims to evaluate the temporal post-disaster patterns of selected diseases after a flood, an earthquake, and a typhoon in the Philippines in 2013. METHODOLOGY: We analyzed the 21 syndromes provided by SPEED both separately and grouped into injuries, communicable diseases, and non communicable diseases (NCDs) by calculating daily post-disaster consultation rates for up to 150 days post-disaster. These were compared over time and juxtaposed according to the type of disaster. RESULTS: Communicable diseases were found to be the predominant syndrome group in all three disaster types. The top six syndromes found were: acute respiratory infections, open wounds, bruises and burns, high blood pressure, skin disease, fever, and acute watery diarrhea. DISCUSSION: Overall, the results aligned with the country's morbidity profile. Within 2 months, the clear gradation of increasing syndrome rates reflected the severity (flood=70 years, race, ethnicity and baseline glycaemic status did not. Compared with a reference subject weighing 100 kg, exposure of liraglutide 3.0 mg was 44 % lower for a subject weighing 234 kg (90 % CI 41-47), 41 % higher for a subject weighing 60 kg (90 % CI 37-46), and 32 % higher (90 % CI 28-35) in females than males with the same body weight. Neither injection site nor renal function significantly influenced exposure of liraglutide 3.0 mg (post hoc analysis). CONCLUSION: Population pharmacokinetics of liraglutide up to and including 3.0 mg daily in overweight and obese adults demonstrated dose-proportional exposure, and limited effect of covariates other than sex and body weight. These findings were similar to those previously observed with liraglutide up to 1.8 mg in subjects with type 2 diabetes mellitus. Further analysis of exposure-response relationship and its effect on dose requirements is addressed in a separate publication. PMID- 27193273 TI - Are Aristolochic Acids Responsible for the Chemical Defence of Aposematic Larvae of Battus polydamas (L.) (Lepidoptera: Papilionidae)? AB - Aristolochic acids (AAs) are thought to be responsible for the chemical protection of the aposematic larvae Battus polydamas (L.) (Papilionidae: Troidini) against predators. These compounds are sequestered by larvae from their Aristolochia (Aristolochiaceae) host plants. Studying the role of the chemical protection of the second and fifth instars of B. polydamas against potential predators, we found that the consumption of larvae by the carpenter ant Camponotus crassus Mayr and young chicks Gallus gallus domesticus was dependent on larval developmental stage. Second instars were more preyed upon than fifth instars; however, the assassin bug Montina confusa Stal was not deterred by chemical defences of the fifth instar B. polydamas. Laboratory bioassays with carpenter ants and young chicks using palatable baits topically treated with a pure commercial mixture of AAs I and AAs II in concentrations up to 100 times those previously found in B. polydamas larvae showed no activity. Similar results were found in field bioassays, where palatable baits treated as above were exposed to the guild of predators that attack B. polydamas larvae and were also consumed irrespective of the commercial AA concentration used. These results suggest that the mixture of AAs I and AAs II have no defensive role against predators, at least against those investigated in the present work. Other compounds present in Aristolochia host plants such as O-glycosylated AAs; benzylisoquinoline alkaloids; and mono-, sesqui-, di-, and triterpenes, which can be sequestered by Troidini, could act as deterrents against predators. PMID- 27193275 TI - Influence of Apis mellifera L. (Hymenoptera: Apidae) on the Use of the Most Abundant and Attractive Floral Resources in a Plant Community. AB - Some factors influence the distribution of abundance of floral visitors, especially the amount and quality of the floral resources available, the size of the area occupied by the visitor, habitat heterogeneity, and the impact caused by natural enemies and introduced species. The objective of this research was to evaluate the distribution of abundance of the foraging activity of native floral visitors and Apis mellifera L. in the most abundant and attractive food sources in a secondary forest fragment with features of Cerrado-Atlantic Forest. Some plant species were selected and the frequency of foraging made by floral visitors was recorded. A high abundance of visits in flowers was performed by A. mellifera. Two factors may have influenced this result: (1) the occupation of the forest fragment predominantly by vines and shrubs at the expenses of vegetation with arboreal characteristics that favored the encounter of the flowering plants by A. mellifera; (2) rational beekeeping of A. mellifera, causing the number of natural swarms which originate annually from colonies of commercial apiaries and colonies previously established in the environment to be very high, thus leading to an increase in the population size of this bee species in the study site. The frequent occurrence of human-induced fire and deforestation within the forest fragment may have reduced the population size of the bee species, including A. mellifera. As the populations of A. mellifera have the capacity to quickly occupy the environment, this species possibly became dominant after successive disturbances made in the forest fragment. PMID- 27193274 TI - Species Diversity and Temporal Variation of the Orchid-Bee Fauna (Hymenoptera, Apidae) in a Conservation Gradient of a Rocky Field Area in the Espinhaco Range, State of Minas Gerais, Southeastern Brazil. AB - This study investigated the orchid-bee community in a conservation gradient of the high-altitude rocky fields in the state of Minas Gerais, Brazil. Sampling was performed at two sites with different anthropic influences: a disturbed area (DA), with exotic plant species, and a preserved area (PA). From September 2009 through February 2011, males of euglossine bees were sampled using aromatic bait traps. We collected a total of 819 specimens belonging to 11 species and three genera: Euglossa Latreille, Eulaema Lepeletier, and Eufriesea Cockerell. Despite the proximity of DA and PA (about 1.2 km), differences in orchid-bee abundance and richness were observed. Higher abundance was observed in the PA (n = 485) compared with the DA (n = 334). Eight species were common to both sites, and only the DA showed exclusive species. The DA showed higher diversity and higher estimated species richness. Euglossa leucotricha Rebelo & Moure was the most abundant species at both sites followed by Euglossa melanotricha Moure. Higher abundance and richness were found in the warm rainy season. This study contributes to the knowledge of the orchid-bee fauna in the rocky fields and suggests that the greater resource availability in the DA was responsible for the higher orchid-bee diversity. PMID- 27193276 TI - Development and Leaf Consumption by Spodoptera cosmioides (Walker) (Lepidoptera: Noctuidae) Reared on Leaves of Agroenergy Crops. AB - Spodoptera cosmioides (Walker) (Lepidoptera: Noctuidae) is a polyphagous pest that threatens more than 24 species of crop plants including those used for biodiesel production such as Ricinus communis (castor bean), Jatropha curcas (Barbados nut), and Aleurites fordii (tung oil tree). The development and leaf consumption by S. cosmioides reared on leaves of these three species were studied under controlled laboratory conditions. The egg-to-adult development time of S. cosmioides was shortest when reared on castor bean leaves and longest when reared on tung oil tree leaves. Larvae reared on castor bean and Barbados nut leaves had seven instars, whereas those reared on tung oil tree leaves had eight. Females originating from larvae reared on castor bean and Barbados nut leaves showed greater fecundity than did females originating from larvae reared on tung oil tree leaves. Insects fed on castor bean leaves had shorter life spans than those fed on tung oil tree and Barbados nut leaves although the oviposition period did not differ significantly. The intrinsic and finite rates of increase were highest for females reared on castor bean leaves. Total leaf consumption was highest for larvae reared on tung oil tree leaves and lowest for those reared on Barbados nut leaves. We conclude that castor bean is a more appropriate host plant for the development of S. cosmioides than are Barbados nut and tung oil tree. PMID- 27193277 TI - Egg Phenology of a Host-Specialist Butterfly in the Western Slopes of the Northern Chilean Andes. AB - Phenological studies are especially important in order to understand the ecological process operating at temporal level. The western slopes of the northern Chilean Andes at about 3,500 m asl are a mosaic of arid environments in which precipitations are highly seasonal, mostly concentrated in summer. Teriocolias zelia andina Forbes (Lepidoptera: Pieridae) is one of the most conspicuous and regularly observed butterflies flying in this region; it is a host specialist associated with the native shrub Senna birostris var. arequipensis (Fabaceae). The objectives of this study were (1) to characterize the temporal variations in the relative abundance of eggs of this host-specialist butterfly and (2) to examine the relationship of these variations with leaf phenology. Monthly samplings of eggs were carried out from February 2011 to January 2012. Circular statistical analyses of the relative abundance of eggs indicated clustered distribution along the year with the mean vector in June. Temporal variation in the relative abundance of eggs was correlated (Spearman rank correlation test) with the availability of plant substrate for egg laying and larval feeding. PMID- 27193279 TI - Distribution, Abundance and Molecular Analysis of Genus Barbadocladius Cranston & Krosch (Diptera, Chironomidae) in Tropical, High Altitude Andean Streams and Rivers. AB - The distribution of the genus Barbadocladius Cranston & Krosch (Diptera: Chironomidae), previously reported from Chile to Bolivia, has extended northwards. Larvae, pupae and pupal exuviae of this genus have been found in the high mountain tropical streams of Peru to 9 degrees 22'56", but are restricted to very high altitude streams (altitudes over 3,278 m asl) compared to the lower altitude streams (below 1,100 m asl) in which the genus is reported in Chile and Argentina. Based on morphological studies, both described species in the genus, Barbadocladius andinus Cranston & Krosch and Barbadocladius limay Cranston & Krosch, have been found in Peru as pupae or pupal exuviae. Morphological analysis of the larvae and pupae revealed no differences between the two described species from Patagonia and Peru, which are of similar size and with a similar armament of hooklets and spines in pupal tergites and sternites. However, molecular analysis of larvae and pupae revealed that in Peru, there are at least two different evolutionary lines, one distributed widely and another restricted to one site. Phylogenetic analysis (using cox1 mitochondrial sequences) of all available sequences of Barbadocladius shows that the Chilean and Argentinean material differs from that of Peru. Therefore, a total of four molecular segregates are identified, although morphologically, neither larvae nor the pupae may be differentiated. PMID- 27193278 TI - Sexual Size Dimorphism in the Color Pattern Elements of Two Mimetic Heliconius Butterflies. AB - Sexual dichromatism and sexual dimorphism of body size are reasonably well studied in butterflies. Sexual size dimorphism of color pattern elements, however, is much less explored. The object of this study is Heliconius, a genus of butterflies well known for the coevolution between mate color preferences and mimicry. Given the sexual role of wing coloration, we investigated the existence of sexual size dimorphism in the wing color elements of a mimetic pair-Heliconius erato phyllis Fabricius and Heliconius besckei Menetries-and analyzed the allometric patterns of these traits. Correlation between size of elements in the dorsal and ventral wing surfaces were also estimated. In both species, three out of four elements were larger in males, but the non-dimorphic element was not the same. With regard to the allometric patterns, our most important finding was that smaller males of one species have proportionally larger yellow bars. This is the first study specifically concerning quantitative sexual dimorphism in the coloration of this well-known genus of butterflies and it opens new prospects to investigate sex-related natural selection and sexual selection of color pattern elements. PMID- 27193280 TI - The Identity of Specimens of the Anastrepha fraterculus Complex (Diptera, Tephritidae) with Atypical Aculeus Tip. AB - Several specimens collected in Paraguay along with Anastrepha fraterculus (sensu lato) have an aculeus tip similar to species from the fraterculus complex, but the teeth of the aculeus of these specimens are poorly defined. As Anastrepha species identification is based mostly on subtle differences in the aculeus tip, we studied these specimens with atypical aculeus tips (with poorly defined teeth) that slightly differs from the aculeus tip of species of the fraterculus complex (with well-developed blunt teeth), to determine if this is due to intraspecific variation or if it can characterize a full species. The Paraguayan specimens were separated in six groups under stereomicroscope according to variation in their aculeus tip. Specimens within each group were studied by means of morphometrics (traditional and geometric) and gene sequence analysis (COI and ITS1). Morphometric analyses were significant, but no clear groups were formed by the discriminant analyses of the aculeus and wing, and the COI and ITS1 sequence analysis clustered specimens with all six aculeus variations. Therefore, the subtle morphological differences observed in the aculeus tip of Paraguayan specimens are intraspecific variations and the Paraguayan specimens were more genetically closely related to Anastrepha sp. 3 from the fraterculus complex. PMID- 27193281 TI - Aphid Species and Population Dynamics Associated with Strawberry. AB - Aphids are among the major pests associated with strawberries in Southern Brasil. In this study, we identified the main species that occur in strawberry fields in the states of Parana and Rio Grande do Sul, Brasil. We also compared the effectiveness of different sampling methods and studied the population dynamics of aphid species during two strawberry crop cycles in the municipality of Pinhais, state of Parana, Brasil. Chaetosiphon fragaefolii (Cockerell) and Aphis forbesi Weed were the main species associated with strawberry. The method of hit plant and the Moericke trap showed equal effectiveness to capture wingless and winged insects. The peak population of aphids in the state of Parana occurred from September to November. This information can help producers to implement strategies to monitor and control the major aphid species that occur in strawberry culture. PMID- 27193282 TI - Effects of Pepper (Capsicum annuum) Cultivars on the Biology and Life Table Parameters of Myzus persicae (Sulz.) (Hemiptera: Aphididae). AB - Green peach aphids, Myzus persicae (Sulz.) (Hemiptera: Aphididae), obtained from pepper fields, were colonized on susceptible pepper plants in a growth chamber. The development, survivorship, and life table parameters of the green peach aphid were evaluated on nine peppers cultivars as follows: Almuden, Bilano, Bird, Cabezo, de la Sierra, Eppo, Jaen, Raza, and Yatasto at controlled conditions (20 +/- 1 degrees C; about 70% RH; 14h photophase). The development times of immatures ranged from 6.1 days on Yatasto to 11.4 days on Jaen, whereas immature survival was close to 100% on all cultivars. The intrinsic rate of increase (r m ) for green peach aphid on Bilano and Yatasto were the highest. Jackknife estimates of r m varied from 0.281 to 0.174 females/female/day on Yatasto and Jaen, respectively. The mean population generation times (T) on these hosts ranged from 13.7 to 22.7 days. The highest net reproductive rates (R 0 ) were on Bird and Bilano (63.8 and 62.89 females/female/generation, respectively) and the lowest on De la Sierra and Almuden (34.1 and 38.7, respectively). Because of the high coefficient of determination (R (2)) values in Gompertz and Weibul models, survival data from different cultivars had a good fit to both models. The results pointed Jaen, Almuden, and Raza cultivars as the least suitable host plants, indicating that they were the most resistant to M. persicae among the cultivars we tested. PMID- 27193283 TI - Assessment of Insecticidal Efficacy of Diatomaceous Earth and Powders of Common Lavender and Field Horsetail against Bean Weevil Adults. AB - In the search for an effective and sustainable control method against the bean weevil Acanthoscelides obtectus (Say), an important insect pest affecting stored common beans and other legumes, three different powders were tested against adult been weevils under laboratory conditions. The three powders were diatomaceous earth (DE) (commercial product SilicoSec(r)), common lavender (Lavandula angustifolia) powder and field horsetail (Equisetum arvense) powder. The substances were tested at five temperatures (15, 20, 25, 30, and 35 degrees C), two relative humidity levels (RH) (55 and 75%), and four concentrations (100, 300, 500, and 900 ppm). The mortality of adults was measured after the 1st, 2nd, 4th, and 7th days of exposure. The efficacy of the powders increased with the temperature, whereas in general, RH did not have a significant effect on the adults' survival. According to common practice of storing common beans, we recommend the use of DE against the pest in question, as this inert powder showed the highest efficacy at lower temperatures and concentrations. Concerning the wider use of common lavender and field horsetail powders, we suggest studying their combined use with other environmentally friendly methods with the aim of achieving the highest synergistic effect possible. PMID- 27193284 TI - Activity in the fronto-parietal network indicates numerical inductive reasoning beyond calculation: An fMRI study combined with a cognitive model. AB - Numerical inductive reasoning refers to the process of identifying and extrapolating the rule involved in numeric materials. It is associated with calculation, and shares the common activation of the fronto-parietal regions with calculation, which suggests that numerical inductive reasoning may correspond to a general calculation process. However, compared with calculation, rule identification is critical and unique to reasoning. Previous studies have established the central role of the fronto-parietal network for relational integration during rule identification in numerical inductive reasoning. The current question of interest is whether numerical inductive reasoning exclusively corresponds to calculation or operates beyond calculation, and whether it is possible to distinguish between them based on the activity pattern in the fronto parietal network. To directly address this issue, three types of problems were created: numerical inductive reasoning, calculation, and perceptual judgment. Our results showed that the fronto-parietal network was more active in numerical inductive reasoning which requires more exchanges between intermediate representations and long-term declarative knowledge during rule identification. These results survived even after controlling for the covariates of response time and error rate. A computational cognitive model was developed using the cognitive architecture ACT-R to account for the behavioral results and brain activity in the fronto-parietal network. PMID- 27193285 TI - Delivering a quality-assured fracture liaison service in a UK teaching hospital is it achievable? AB - To determine whether new national guidance on the specifications of a fracture liaison service are realistically deliverable, 1 year of data on the performance of such a service were audited. Audit targets were mostly met. This audit demonstrates that these standards are deliverable in a real world setting. INTRODUCTION: UK service specifications for a fracture liaison service (FLS) have been produced (National Osteoporosis Society, NOS) to promote effective commissioning and delivery of the highest quality care to patients with fragility fractures. How deliverable these standards are has not as yet been methodically reported. Our FLS was modelled on the ten NOS standards; performance was audited after 1 year to determine whether these standards could be delivered and to describe the lessons learnt. METHODS: Performance was audited against the NOS FLS Service Standards, with management based on the Fracture Risk Assessment Tool (FRAX(r)), the four-item Falls Risk Assessment Tool (FRAT), National Institute for Health and Care Excellence (NICE) and the National Osteoporosis Guideline Groups (NOGG) guidance. Data were recorded prospectively on a database. The FLS commenced in May 2014, was fully operational in August 2014 and data were captured from 1 September 2014 to 1 September 2015. RESULTS: The FLS detected 1773 patients and standards were largely achieved. Most, 94 %, patients were seen within 6 weeks, 533 DXA requests were generated, 804 outpatient FRAT assessments were recorded (134 required falls intervention) and 773 patients had bone treatments started. On follow-up at 3 months, between 78-79 % were still taking medication. CONCLUSIONS: Preliminary evaluation of a FLS implemented according to UK NOS standards demonstrates that the model is practical to apply to a large teaching hospital population. Collection and review of outcome and cost effectiveness data is required to determine the performance of this model in comparison with existing models. PMID- 27193286 TI - [Molecular epidemiology of phlebovirus in four provinces in Morocco]. AB - Sandflies are vectors of protozoa, viruses, and bacteria. To investigate the transmission of phleboviruses, a total of 8753 sandflies were collected in four foci of leishmania. A total of 16 distinct species were morphologically identified. Nested-PCR and cell culture screening for phleboviruses, using an assay targeting the polymerase gene, showed positive results for 19 pools of sandflies. Sequencing of the corresponding products confirmed the results and allowed identification of Toscana virus exclusively. Corresponding sandfly species originated from four different foci, and were different from those commonly reported in the literature. Sequence analysis shows that the Moroccan Toscana viruses belong to genotype B and appear close to the Toscana viruses isolated in France and Spain. This study reported the existence of the virus in the north, center and south of the country. The abundance and diversity of sandflies in Morocco, Mediterranean climate, would support the continuous circulation of Toscana virus in our country, posing a potential risk of emergence of these arboviruses. PMID- 27193288 TI - Teaching Real Data Interpretation with Models (TRIM): Analysis of Student Dialogue in a Large-Enrollment Cell and Developmental Biology Course. AB - We present our design for a cell biology course to integrate content with scientific practices, specifically data interpretation and model-based reasoning. A 2-yr research project within this course allowed us to understand how students interpret authentic biological data in this setting. Through analysis of written work, we measured the extent to which students' data interpretations were valid and/or generative. By analyzing small-group audio recordings during in-class activities, we demonstrated how students used instructor-provided models to build and refine data interpretations. Often, students used models to broaden the scope of data interpretations, tying conclusions to a biological significance. Coding analysis revealed several strategies and challenges that were common among students in this collaborative setting. Spontaneous argumentation was present in 82% of transcripts, suggesting that data interpretation using models may be a way to elicit this important disciplinary practice. Argumentation dialogue included frequent co-construction of claims backed by evidence from data. Other common strategies included collaborative decoding of data representations and noticing data patterns before making interpretive claims. Focusing on irrelevant data patterns was the most common challenge. Our findings provide evidence to support the feasibility of supporting students' data-interpretation skills within a large lecture course. PMID- 27193287 TI - A meta-review of stress, coping and interventions in dementia and dementia caregiving. AB - BACKGROUND: There has been a substantial number of systematic reviews of stress, coping and interventions for people with dementia and their caregivers. This paper provides a meta-review of this literature 1988-2014. METHOD: A meta-review was carried out of systematic reviews of stress, coping and interventions for people with dementia and their caregivers, using SCOPUS, Google Scholar and CINAHL Plus databases and manual searches. RESULTS: The meta-review identified 45 systematic reviews, of which 15 were meta-analyses. Thirty one reviews addressed the effects of interventions and 14 addressed the results of correlational studies of factors associated with stress and coping. Of the 31 systematic reviews dealing with intervention studies, 22 focused on caregivers, 6 focused on people with dementia and 3 addressed both groups. Overall, benefits in terms of psychological measures of mental health and depression were generally found for the use of problem focused coping strategies and acceptance and social-emotional support coping strategies. Poor outcomes were associated with wishful thinking, denial, and avoidance coping strategies. The interventions addressed in the systematic reviews were extremely varied and encompassed Psychosocial, Psychoeducational, Technical, Therapy, Support Groups and Multicomponent interventions. Specific outcome measures used in the primary sources covered by the systematic reviews were also extremely varied but could be grouped into three dimensions, viz., a broad dimension of "Psychological Well-Being v. Psychological Morbidity" and two narrower dimensions of "Knowledge and Coping" and of "Institutionalisation Delay". CONCLUSIONS: This meta-review supports the conclusion that being a caregiver for people with dementia is associated with psychological stress and physical ill-health. Benefits in terms of mental health and depression were generally found for caregiver coping strategies involving problem focus, acceptance and social-emotional support. Negative outcomes for caregivers were associated with wishful thinking, denial and avoidance coping strategies. Psychosocial and Psychoeducational interventions were beneficial for caregivers and for people with dementia. Support groups, Multicomponent interventions and Joint Engagements by both caregivers and people with dementia were generally found to be beneficial. It was notable that virtually all reviews addressed very general coping strategies for stress broadly considered, rather than in terms of specific remedies for specific sources of stress. Investigation of specific stressors and remedies would seem to be a useful area for future research. PMID- 27193289 TI - Practices and Perspectives of College Instructors on Addressing Religious Beliefs When Teaching Evolution. AB - Evolution is a core concept of biology, and yet many college biology students do not accept evolution because of their religious beliefs. However, we do not currently know how instructors perceive their role in helping students accept evolution or how they address the perceived conflict between religion and evolution when they teach evolution. This study explores instructor practices and beliefs related to mitigating students' perceived conflict between religion and evolution. Interviews with 32 instructors revealed that many instructors do not believe it is their goal to help students accept evolution and that most instructors do not address the perceived conflict between religion and evolution. Instructors cited many barriers to discussing religion in the context of evolution in their classes, most notably the instructors' own personal beliefs that religion and evolution may be incompatible. These data are exploratory and are intended to stimulate a series of questions about how we as college biology instructors teach evolution. PMID- 27193290 TI - Changes in Biology Self-Efficacy during a First-Year University Course. AB - Academic self-efficacy encompasses judgments regarding one's ability to perform academic tasks and is correlated with achievement and persistence. This study describes changes in biology self-efficacy during a first-year course. Students (n = 614) were given the Biology Self-Efficacy Scale at the beginning and end of the semester. The instrument consisted of 21 questions ranking confidence in performing biology-related tasks on a scale from 1 (not at all confident) to 5 (totally confident). The results demonstrated that students increased in self efficacy during the semester. High school biology and chemistry contributed to self-efficacy at the beginning of the semester; however, this relationship was lost by the end of the semester, when experience within the course became a significant contributing factor. A proportion of high- and low- achieving (24 and 40%, respectively) students had inaccurate self-efficacy judgments of their ability to perform well in the course. In addition, female students were significantly less confident than males overall, and high-achieving female students were more likely than males to underestimate their academic ability. These results suggest that the Biology Self-Efficacy Scale may be a valuable resource for tracking changes in self-efficacy in first-year students and for identifying students with poorly calibrated self-efficacy perceptions. PMID- 27193291 TI - A Conceptual Framework for Graduate Teaching Assistant Professional Development Evaluation and Research. AB - Biology graduate teaching assistants (GTAs) are significant contributors to the educational mission of universities, particularly in introductory courses, yet there is a lack of empirical data on how to best prepare them for their teaching roles. This essay proposes a conceptual framework for biology GTA teaching professional development (TPD) program evaluation and research with three overarching variable categories for consideration: outcome variables, contextual variables, and moderating variables. The framework's outcome variables go beyond GTA satisfaction and instead position GTA cognition, GTA teaching practice, and undergraduate learning outcomes as the foci of GTA TPD evaluation and research. For each GTA TPD outcome variable, key evaluation questions and example assessment instruments are introduced to demonstrate how the framework can be used to guide GTA TPD evaluation and research plans. A common conceptual framework is also essential to coordinating the collection and synthesis of empirical data on GTA TPD nationally. Thus, the proposed conceptual framework serves as both a guide for conducting GTA TPD evaluation at single institutions and as a means to coordinate research across institutions at a national level. PMID- 27193293 TI - Quantification of the HIV transcriptional activator complex in live cells by image-based protein-protein interaction analysis. AB - The virus-encoded Tat protein is essential for HIV transcription in infected cells. The interaction of Tat with the cellular transcription elongation factor P TEFb (positive transcriptional elongation factor b) containing cyclin T1 (CycT1) and cyclin-dependent kinase 9 (CDK9) is critical for its activity. In this study, we use the Fluoppi (fluorescent-based technology detecting protein-protein interaction) system, which enables the quantification of interactions between biomolecules, such as proteins, in live cells. Quantitative measurement of the molecular interactions among Tat, CycT1 and CDK9 has showed that any third molecule enhances the binding between the other two molecules. These findings suggest that each component of the Tat:P-TEFb complex stabilizes the overall complex, thereby supporting the efficient transcriptional elongation during viral RNA synthesis. These interactions may serve as appropriate targets for novel anti HIV therapy. PMID- 27193292 TI - Isolating RNA from precursor and mature melanocytes from human vitiligo and normal skin using laser capture microdissection. AB - To characterize the gene expression profile of regenerated melanocytes in the narrow band UVB (NBUVB)-treated vitiligo epidermis and their precursors in the hair follicle, we present here a strategy of RNA isolation from in situ melanocytes using human frozen skin. We developed a rapid immunostaining protocol using the NKI-beteb antibody, which labels differentiated and precursor melanocytes, followed by fluorescent laser capture microdissection. This technique enabled the direct isolation, from melanocyte and adjacent keratinocyte populations, of satisfactory quality RNA that was successfully amplified and analysed by qRT-PCR. The melanocyte-specific gene transcripts TYR, DCT, TYRP1 and PMEL were significantly upregulated in our NBUVB-treated melanocyte samples as compared with the keratinocyte samples, while keratinocyte-specific genes (KRT5 and KRT14) were expressed significantly higher in the keratinocyte samples as compared with the melanocyte samples. Furthermore, in both NBUVB-treated vitiligo skin and normal skin, when bulge melanocytes were compared with epidermal melanocytes, we found significantly lower expression of melanocyte-specific genes and significantly higher expression of three melanocytic stem cell genes (SOX9, WIF1 and SFRP1), while ALCAM and ALDH1A1 transcripts did not show significant variation. We found significantly higher expression of melanocyte-specific genes in the epidermis of NBUVB-treated vitiligo, as compared to the normal skin. When comparing bulge melanocyte samples from untreated vitiligo, NBUVB-treated vitiligo and normal skin, we did not find significant differences in the expression of melanocyte-specific genes or melanocytic stem cell genes. These techniques offer valuable opportunities to study melanocytes and their precursors in vitiligo and other pigmentation disorders. PMID- 27193294 TI - Subcutaneous Phaeohyphomycosis Cyst Associated with Medicopsis romeroi in an Immunocompromised Host. AB - An 88-year-old man, receiving prednisolone for sarcoidosis, presented with a discrete keratotic lesion on the dorsum of his right hand following the placement of an intravenous cannula a month prior to its appearance. Medicopsis romeroi was isolated from the tissue and identified by sequencing the internal transcribed spacer region ITS-1 and the D1-2 fragment of the 28S rDNA gene. Histopathological examination showed fungal hyphae in the internal inflammatory cells layer and within the histocyte-macrophage layer, highly suggestive of deep mycosis. The patient was successfully treated with surgical excision of the cyst. M. romeroi exhibited high MIC values for echinocandin drugs in vitro, but appeared susceptible to newer triazole agents, amphotericin B and terbinafine. This is the first report of a subcutaneous phaeohyphomycotic cyst occurring following the placement of an intravenous cannula. This report highlights the potential role of M. romeroi as an emerging cause of deep, non-mycetomatous infection in immunocompromised patients. PMID- 27193295 TI - Virulence Attributes and Antifungal Susceptibility Profile of Opportunistic Fungi Isolated from Ophthalmic Infections. AB - Investigations of both virulence factors and antifungal susceptibility profiles are crucial for understanding the pathogenesis and prognosis of ophthalmic mycoses. In this study, we investigated the in vitro antifungal susceptibility of amphotericin B (AMB), voriconazole (VRC), and natamycin (NAT) against a set of 50 fungal isolates obtained from patients with ocular mycoses using the Clinical and Laboratory Standards Institute broth microdilution method. In addition, putative virulence factor, such as secretory phospholipases and proteinases, and biofilm formation activity were analyzed. The geometric means (GMs) of the minimum inhibitory concentrations (MICs) of the antifungals across all isolates were the following (in increasing order): VRC (0.70 MUg/mL), AMB (0.81 MUg/mL), and NAT (1.05 MUg/mL). The highest activity against 14 Aspergillus strains was exhibited by VRC (GM MIC: 0.10 MUg/mL), followed by AMB and NAT (GM MICs: 0.21 and 0.27 MUg/mL), respectively. However, for 12 Fusarium spp., the GM MIC of VRC (2.66) was higher than those of NAT and AMB (GM MICs 1.3 and 0.8 MUg/mL, respectively). Proteinase and phospholipase activity were observed in 30 % and 42 % of the isolates, respectively, whereas only 8 % of the isolates were able to produce biofilms. Phospholipase activity was observed in all Fusarium isolates, but not in any of the Aspergillus isolates. In contrast, biofilm-forming capability was detected in 25 % of the Fusarium isolates, but none of the Aspergillus isolates. The differences in the MICs of AMB, VRC, and NAT, biofilm-forming ability and proteinase and phospholipase activities among the isolates were not significant (p > 0.05). Overall, our study suggests no significant correlation between the antifungal susceptibility profiles and virulence attributes of ocular fungal isolates. PMID- 27193296 TI - Individual-based versus aggregate meta-analysis in multi-database studies of pregnancy outcomes: the Nordic example of selective serotonin reuptake inhibitors and venlafaxine in pregnancy. AB - PURPOSE: Compare analyses of a pooled data set on the individual level with aggregate meta-analysis in a multi-database study. METHODS: We reanalysed data on 2.3 million births in a Nordic register based cohort study. We compared estimated odds ratios (OR) for the effect of selective serotonin reuptake inhibitors (SSRI) and venlafaxine use in pregnancy on any cardiovascular birth defect and the rare outcome right ventricular outflow tract obstructions (RVOTO). Common covariates included maternal age, calendar year, birth order, maternal diabetes, and co medication. Additional covariates were added in analyses with country-optimized adjustment. RESULTS: Country adjusted OR (95%CI) for any cardiovascular birth defect in the individual-based pooled analysis was 1.27 (1.17-1.39), 1.17 (1.07 1.27) adjusted for common covariates and 1.15 (1.05-1.26) adjusted for all covariates. In fixed effects meta-analyses pooled OR was 1.29 (1.19-1.41) based on crude country specific ORs, 1.19 (1.09-1.29) adjusted for common covariates, and 1.16 (1.06-1.27) for country-optimized adjustment. In a random effects model the adjusted OR was 1.07 (0.87-1.32). For RVOTO, OR was 1.48 (1.15-1.89) adjusted for all covariates in the pooled data set, and 1.53 (1.19-1.96) after country optimized adjustment. Country-specific adjusted analyses at the substance level were not possible for RVOTO. CONCLUSION: Results of fixed effects meta-analysis and individual-based analyses of a pooled dataset were similar in this study on the association of SSRI/venlafaxine and cardiovascular birth defects. Country optimized adjustment attenuated the estimates more than adjustment for common covariates only. When data are sparse pooled data on the individual level are needed for adjusted analyses. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27193297 TI - Only Making Things Worse: A Qualitative Study of the Impact of Wrongly Removing Disability Benefits from People with Mental Illness. AB - Many countries belonging to the Organisation for Economic Co-operation and Development (OECD) have seen a considerable increase in the number of disability benefits recipients (DBRs), in addition to an increase in the proportion of people with mental illness. As in other countries, changes to the welfare benefits system in England were made in order to reduce the number of DBRs. Many people lost their benefit payments, although a considerable number had them reinstated after appeal. Our aim was to investigate the impact of the process on DBRs whose disability was related to mental health and who won their appeal. Seventeen DBRs were interviewed. The participants reported three main types of impact. Beyond the practical reduction of income and the related anxiety, interviewees reported considerable stress when coping with the 'never-ending' cycle of bureaucracy. They also expressed anger, frustration and demoralisation at mistrust on the part of the authorities partly due to the 'invisibility' of their disability. PMID- 27193298 TI - PACRG, a protein linked to ciliary motility, mediates cellular signaling. AB - Cilia are microtubule-based organelles that project from nearly all mammalian cell types. Motile cilia generate fluid flow, whereas nonmotile (primary) cilia are required for sensory physiology and modulate various signal transduction pathways. Here we investigate the nonmotile ciliary signaling roles of parkin coregulated gene (PACRG), a protein linked to ciliary motility. PACRG is associated with the protofilament ribbon, a structure believed to dictate the regular arrangement of motility-associated ciliary components. Roles for protofilament ribbon-associated proteins in nonmotile cilia and cellular signaling have not been investigated. We show that PACRG localizes to a small subset of nonmotile cilia in Caenorhabditis elegans, suggesting an evolutionary adaptation for mediating specific sensory/signaling functions. We find that it influences a learning behavior known as gustatory plasticity, in which it is functionally coupled to heterotrimeric G-protein signaling. We also demonstrate that PACRG promotes longevity in C. elegans by acting upstream of the lifespan promoting FOXO transcription factor DAF-16 and likely upstream of insulin/IGF signaling. Our findings establish previously unrecognized sensory/signaling functions for PACRG and point to a role for this protein in promoting longevity. Furthermore, our work suggests additional ciliary motility-signaling connections, since EFHC1 (EF-hand containing 1), a potential PACRG interaction partner similarly associated with the protofilament ribbon and ciliary motility, also positively regulates lifespan. PMID- 27193299 TI - Defining the functional binding sites of interleukin 12 receptor beta1 and interleukin 23 receptor to Janus kinases. AB - The interleukin (IL)-12-type cytokines IL-12 and IL-23 are involved in T-helper (Th) 1 and Th17 immunity, respectively. They share the IL-12 receptor beta1 (IL 12Rbeta1) as one component of their receptor signaling complexes, with IL 12Rbeta2 as second receptor for IL-12 and IL-23R for IL-23 signal transduction. Stimulation with IL-12 and IL-23 results in activation of receptor-associated Janus kinases (Jak) and phosphorylation of STAT proteins in target cells. The Janus kinase tyrosine kinase (Tyk) 2 associates with IL-12Rbeta1, whereas Jak2 binds to IL-23R and also to IL-12Rbeta2. Receptor association of Jak2 is mediated by Box1 and Box2 motifs located within the intracellular domain of the receptor chains. Here we define the Box1 and Box2 motifs in IL-12Rbeta1 and an unusual Jak2-binding site in IL-23R by the use of deletion and site-directed mutagenesis. Our data show that nonfunctional box motifs abolish IL-12- and IL-23-induced STAT3 phosphorylation and cytokine-dependent proliferation of Ba/F3 cells. Coimmunoprecipitation of Tyk2 by IL-12Rbeta1 and Jak2 by IL-23R supported these findings. In addition, our data demonstrate that association of Jak2 with IL-23R is mandatory for IL-12 and/or IL-23 signaling, whereas Tyk2 seems to be dispensable. PMID- 27193300 TI - Virtual-tissue computer simulations define the roles of cell adhesion and proliferation in the onset of kidney cystic disease. AB - In autosomal dominant polycystic kidney disease (ADPKD), cysts accumulate and progressively impair renal function. Mutations in PKD1 and PKD2 genes are causally linked to ADPKD, but how these mutations drive cell behaviors that underlie ADPKD pathogenesis is unknown. Human ADPKD cysts frequently express cadherin-8 (cad8), and expression of cad8 ectopically in vitro suffices to initiate cystogenesis. To explore cell behavioral mechanisms of cad8-driven cyst initiation, we developed a virtual-tissue computer model. Our simulations predicted that either reduced cell-cell adhesion or reduced contact inhibition of proliferation triggers cyst induction. To reproduce the full range of cyst morphologies observed in vivo, changes in both cell adhesion and proliferation are required. However, only loss-of-adhesion simulations produced morphologies matching in vitro cad8-induced cysts. Conversely, the saccular cysts described by others arise predominantly by decreased contact inhibition, that is, increased proliferation. In vitro experiments confirmed that cell-cell adhesion was reduced and proliferation was increased by ectopic cad8 expression. We conclude that adhesion loss due to cadherin type switching in ADPKD suffices to drive cystogenesis. Thus, control of cadherin type switching provides a new target for therapeutic intervention. PMID- 27193301 TI - Clustered nuclei maintain autonomy and nucleocytoplasmic ratio control in a syncytium. AB - Nuclei in syncytia found in fungi, muscles, and tumors can behave independently despite cytoplasmic translation and the homogenizing potential of diffusion. We use a dynactin mutant strain of the multinucleate fungus Ashbya gossypii with highly clustered nuclei to assess the relative contributions of nucleus and cytoplasm to nuclear autonomy. Remarkably, clustered nuclei maintain cell cycle and transcriptional autonomy; therefore some sources of nuclear independence function even with minimal cytosol insulating nuclei. In both nuclear clusters and among evenly spaced nuclei, a nucleus' transcriptional activity dictates local cytoplasmic contents, as assessed by the localization of several cyclin mRNAs. Thus nuclear activity is a central determinant of the local cytoplasm in syncytia. Of note, we found that the number of nuclei per unit cytoplasm was identical in the mutant to that in wild-type cells, despite clustered nuclei. This work demonstrates that nuclei maintain autonomy at a submicrometer scale and simultaneously maintain a normal nucleocytoplasmic ratio across a syncytium up to the centimeter scale. PMID- 27193304 TI - Effects of Manufacturing Conditions on Pharmaceutical Properties of Petrolatum Ointment. AB - Oleaginous white petrolatum ointment (WP ointment) is one of the most commonly used dosage forms in the preparation of topical products. In general, WP ointments containing medium chain fatty acid triglycerides (MCT) are manufactured through a process of melting, mixing, agitating, and cooling. To investigate the pharmaceutical properties of WP ointments in greater detail, we examined manufacturing factors which could potentially influence the pharmaceutical properties of the finished product. WP ointment samples containing 10% MCT were stirred with a homogenizer and a paddle mixer at 65 degrees C, then the homogenizer was stopped. Next, the paddle-mixer was stopped at several planned temperature points at which different samples were taken. Each sample was then cooled under the following planned conditions: rapid-cooling [-50 degrees C/h] and slow-cooling [-7.5 degrees C/h]. The pharmaceutical properties of each WP ointment sample, along with the appearance (Optical/digital microscope), hardness (Rheometer), and bleeding ability (100 Mesh wire-net cone) were measured. Then, release profiles were performed with a WP ointment using the model active ingredient Vitamin D. As a result, high hardness, low bleeding ability and low release profile were observed in the WP ointment samples that were manufactured under the condition of stopping the paddle-mixer at 40 degrees C. However, the influence of cooling speed was observed to affect only hardness. Through optical microscopic observation, it was found that the appearance of WP ointment samples differed depending on the conditions under which they were manufactured. In this study, it was clear that the pharmaceutical properties of WP ointment samples were particularly influenced by the paddle-mixer stopping temperature. PMID- 27193303 TI - Two-ligand priming mechanism for potentiated phosphoinositide synthesis is an evolutionarily conserved feature of Sec14-like phosphatidylinositol and phosphatidylcholine exchange proteins. AB - Lipid signaling, particularly phosphoinositide signaling, plays a key role in regulating the extreme polarized membrane growth that drives root hair development in plants. The Arabidopsis AtSFH1 gene encodes a two-domain protein with an amino-terminal Sec14-like phosphatidylinositol transfer protein (PITP) domain linked to a carboxy-terminal nodulin domain. AtSfh1 is critical for promoting the spatially highly organized phosphatidylinositol-4,5-bisphosphate signaling program required for establishment and maintenance of polarized root hair growth. Here we demonstrate that, like the yeast Sec14, the AtSfh1 PITP domain requires both its phosphatidylinositol (PtdIns)- and phosphatidylcholine (PtdCho)-binding properties to stimulate PtdIns-4-phosphate [PtdIns(4)P] synthesis. Moreover, we show that both phospholipid-binding activities are essential for AtSfh1 activity in supporting polarized root hair growth. Finally, we report genetic and biochemical evidence that the two-ligand mechanism for potentiation of PtdIns 4-OH kinase activity is a broadly conserved feature of plant Sec14-nodulin proteins, and that this strategy appeared only late in plant evolution. Taken together, the data indicate that the PtdIns/PtdCho-exchange mechanism for stimulated PtdIns(4)P synthesis either arose independently during evolution in yeast and in higher plants, or a suitable genetic module was introduced to higher plants from a fungal source and subsequently exploited by them. PMID- 27193302 TI - Coordinate action of distinct sequence elements localizes checkpoint kinase Hsl1 to the septin collar at the bud neck in Saccharomyces cerevisiae. AB - Passage through the eukaryotic cell cycle requires processes that are tightly regulated both spatially and temporally. Surveillance mechanisms (checkpoints) exert quality control and impose order on the timing and organization of downstream events by impeding cell cycle progression until the necessary components are available and undamaged and have acted in the proper sequence. In budding yeast, a checkpoint exists that does not allow timely execution of the G2/M transition unless and until a collar of septin filaments has properly assembled at the bud neck, which is the site where subsequent cytokinesis will occur. An essential component of this checkpoint is the large (1518-residue) protein kinase Hsl1, which localizes to the bud neck only if the septin collar has been correctly formed. Hsl1 reportedly interacts with particular septins; however, the precise molecular determinants in Hsl1 responsible for its recruitment to this cellular location during G2 have not been elucidated. We performed a comprehensive mutational dissection and accompanying image analysis to identify the sequence elements within Hsl1 responsible for its localization to the septins at the bud neck. Unexpectedly, we found that this targeting is multipartite. A segment of the central region of Hsl1 (residues 611-950), composed of two tandem, semiredundant but distinct septin-associating elements, is necessary and sufficient for binding to septin filaments both in vitro and in vivo. However, in addition to 611-950, efficient localization of Hsl1 to the septin collar in the cell obligatorily requires generalized targeting to the cytosolic face of the plasma membrane, a function normally provided by the C terminal phosphatidylserine-binding KA1 domain (residues 1379-1518) in Hsl1 but that can be replaced by other, heterologous phosphatidylserine-binding sequences. PMID- 27193305 TI - A new indole glycoside from the seeds of Raphanus sativus. AB - A new indole glycoside, beta-D-glucopyranosyl 2-(methylthio)-1H-indole-3 carboxylate, named raphanuside A (1), as well as eight known compounds, beta-D fructofuranosyl-(2 -> 1)-(6-O-sinapoyl)-alpha-D-glucopyranoside (2), (3-O sinapoyl)-beta-D-fructofuranosyl-(2 -> 1)-alpha-D-glucopyranoside (3), (3-O sinapoyl)-beta-D-fructofuranosyl-(2 -> 1)-(6-O-sinapoyl)-alpha-D-glucopyranoside (4), (3,4-O-disinapoyl)-beta-D-fructofuranosyl-(2 -> 1)-(6-O-sinapoyl)-alpha-D glucopyranoside (5), isorhamnetin 3,4'-di-O-beta-D-glucoside (6), isorhamnetin 3 O-beta-D-glucoside-7-O-alpha-L-rhamnoside (7), isorhamnetin 3-O-beta-D-glucoside (8) and 3'-O-methyl-(-)-epicatechin 7-O-beta-D-glucoside (9) were isolated from the seeds of Raphanus sativus. Furthermore, compounds 1-3 and 6-9, were isolated from this plant for the first time. The structures of compounds 1-9 were identified using 1D and 2D NMR, including (1)H-(1)H COSY, HSQC, HMBC and NOESY spectroscopic analyses. The inhibitory activity of these isolated compounds against interleukin-6 (IL-6) production in TNF-alpha stimulated MG-63 cells was also examined. PMID- 27193306 TI - Comparison of Radiation Exposure Associated With Intraoperative Cone-Beam Computed Tomography and Follow-up Multidetector Computed Tomography Angiography for Evaluating Endovascular Aneurysm Repairs. AB - PURPOSE: To compare the radiation exposure associated with intraoperative contrast-enhanced cone-beam computed tomography (ceCBCT) acquisitions to standard 3-phase multidetector computed tomography (MDCT) angiography used for assessing technical success after endovascular aortic repair (EVAR). METHODS: Effective doses (EDs) were calculated for 66 EVAR patients (mean age 71 years; 61 men) with a mean 27.7-kg/m(2) body mass index (range 17-49) who had both intraoperative ceCBCT and postoperative 3-phase MDCT angiography between November 2012 and April 2015. In addition, EDs were directly determined using thermoluminescent dosimeters (TLDs) embedded in anthropomorphic phantoms with body mass indexes of 22 and 30 kg/m(2) Effective doses were calculated by summing doses recorded by all TLDs corresponding to a specific tissue type before applying the International Commission on Radiological Protection (ICRP) 60 and 103 weighting factors. EDs were compared with each other for both imaging modalities as well as to TLD measurements. RESULTS: Average EDs of the patient collective were 4.9+/ 1.1 mSv for ceCBCT, 2.6+/-1.2 mSv for single-phase MDCT (46% decrease, covering solely the area of the implanted endograft), and 13.6+/-5.5 mSv for comprehensive 3-phase MDCT examinations (178% increase, anatomical coverage from the aortic arch to femoral artery bifurcation). EDs determined in phantom measurements ranged from 3.1 to 4.5 mSv for ceCBCT, amounting to 2.6 mSv for a single MDCT phase (15% to 40% decrease) using ICRP 60 conversion factors. Applying ICRP 103 factors resulted in higher values for ceCBCT and slightly lower ones for MDCT. CONCLUSION: ceCBCT offers the chance for immediate intraoperative revisions of endograft-related problems. Requiring only a single-phase acquisition, ceCBCT is associated with a considerable reduction in ED (50%-75%) compared to standard 3 phase MDCT angiography after EVAR. On the other hand, MDCT has a larger field of view and is associated with less radiation exposure for a single phase (reduction of 20%-60%) if only the stented region is covered; however, MDCT angiography also uses larger amounts of contrast. PMID- 27193307 TI - Off-Label Iliac Side Branch Application for Salvage of an Accessory Renal Artery. AB - PURPOSE: To present the off-label use of an iliac side branch device to connect an accessory right renal artery to a bifurcated endograft in infrarenal aortic aneurysm repair. CASE REPORT: An 83-year-old woman with a 54-mm infrarenal abdominal aortic aneurysm underwent endovascular repair using an iliac side branch device for accessory renal artery salvage. The procedure was technically successful, and no immediate perioperative adverse events were encountered. The creatinine level increased slightly. Six-month follow-up imaging revealed no endoleaks or occlusion. CONCLUSION: Considering the higher perioperative risk associated with open or hybrid procedures for similar cases, this off-label application of a well-recognized endovascular device deserves consideration as an alternative treatment option. PMID- 27193309 TI - Advances in EEG: home video telemetry, high frequency oscillations and electrical source imaging. AB - Over the last two decades, technological advances in electroencephalography (EEG) have allowed us to extend its clinical utility for the evaluation of patients with epilepsy. This article reviews three main areas in which substantial advances have been made in the diagnosis and pre-surgical planning of patients with epilepsy. Firstly, the development of small portable video-EEG systems have allowed some patients to record their attacks at home, thereby improving diagnosis, with consequent substantial healthcare and economic implications. Secondly, in specialist centres carrying out epilepsy surgery, there has been considerable interest in whether bursts of very high frequency EEG activity can help to determine the regions of the brain likely to be generating the seizures. Identification of these discharges, initially only recorded from intracranial electrodes, may thus allow better surgical planning and improve surgical outcomes. Finally we discuss the contribution of electrical source imaging in the pre-surgical evaluation of patients with focal epilepsy, and its prospects for the future. PMID- 27193308 TI - Twelve-Month Results From the MAJESTIC Trial of the Eluvia Paclitaxel-Eluting Stent for Treatment of Obstructive Femoropopliteal Disease. AB - PURPOSE: To report the 12-month results of the MAJESTIC clinical study of the self-expanding Eluvia paclitaxel-eluting stent in the treatment of femoropopliteal lesions. METHODS: The prospective, single-arm, multicenter trial (clinicaltrials.gov identifier NCT01820637) enrolled 57 patients (mean age 69+/-9 years; 47 men) with chronic lower limb ischemia referable to de novo or restenotic lesions in the native superficial femoral and/or proximal popliteal arteries. A third of the patients had diabetes. Mean lesion length was 70.8+/ 28.1 mm, and diameter stenosis was 86.3%+/-16.2%; 26 (46%) lesions were occluded. Primary patency was defined as duplex ultrasound peak systolic velocity ratio <=2.5 and the absence of target lesion revascularization (TLR) or bypass. Major adverse events (MAEs) included all-cause death through 1 month and target limb major amputation and TLR through 12 months. RESULTS: All 57 patients had a single Eluvia stent implanted, employing pre- and postdilation in 93% (53/57) and 95% (54/57) of cases, respectively. Technical success was 97% (55/57; 2 failures due to residual stenosis >30%). At 12 months, primary patency was 96% (49/51) and the MAE rate was 4% (2/53); both MAEs were TLRs. No stent fractures were identified. There were no major amputations. One death occurred 368 days postprocedure, unrelated to the device or procedure. Improvements in the Rutherford category were sustained through 1 year, with 81% (43/53) exhibiting no symptoms (category 0) and 13% (7/53) presenting with mild claudication (category 1). Mean ABI improved from 0.73+/-0.22 at baseline to 1.02+/-0.20 at 12 months. CONCLUSION: MAJESTIC results showed that patients whose femoropopliteal arteries were treated with the Eluvia drug-eluting stent sustained high patency and low MAE rates through 12 months. PMID- 27193310 TI - Relapse frequency in transitioning from natalizumab to dimethyl fumarate: assessment of risk factors. AB - Risk of relapse after natalizumab (NAT) cessation and switch to dimethyl fumarate (DMF) is unknown. The objective of this paper is to identify the risk and associated risk factors for relapse after switching from NAT to DMF in relapsing remitting multiple sclerosis. Patients (n = 30) were treated with NAT for >=12 months and then switched to DMF in a mean of 50 days. Patient age, annualized relapse rates (ARR), Expanded Disability Status Scale scores (EDSS), and lymphocyte counts were assessed. Overall, eight patients (27 %) had relapses after switching to DMF. Five patients (17 %) suffered severe relapses with multifocal clinical and radiological findings. New lesions by MRI (T2 hyperintense or enhancing) were observed in 35 % of patients. Relapses occurred at a mean of 3.5 months after NAT cessation. Patient age and elevated ARR prior to NAT use were significantly associated with risk of relapse after switch to DMF. Once on DMF for 4 months prior to relapse, lymphocyte count decreased more significantly in patients without relapses than those with relapses. Switching from NAT to DMF correlated with increased relapses. Young patient age, high ARR and stability of lymphocyte counts were risk factors for relapse after transition from NAT to DMF. PMID- 27193311 TI - Postural motor learning in people with Parkinson's disease. AB - Protective postural responses to external perturbations are hypokinetic in people with Parkinson's disease (PD), and improving these responses may reduce falls. However, the ability of people with PD to improve postural responses with practice is poorly understood. Our objective was to determine whether people with PD can improve protective postural responses similarly to healthy adults through repeated perturbations, and whether improvements are retained or generalize to untrained perturbations. Twelve healthy adults and 15 people with PD underwent 25 forward and 25 backward translations of the support surface, eliciting backward, and forward protective steps, respectively. We assessed whether: (1) performance improved over one day of practice, (2) changes were retained 24 h later, and (3) improvements generalized to untrained (lateral) postural responses. People with PD and healthy adults improved postural response characteristics, including center of mass displacement after perturbations (p < 0.001), margin of stability at first footfall (p = 0.001), step latency (p = 0.044), and number of steps (p = 0.001). However, unlike controls, improvements in people with PD occurred primarily in the first block of trials. Improvements were more pronounced during backward protective stepping than forward, and with the exception of step latency, were retained 24 h later. Improvements in forward-backward stepping did not generalize to lateral protective stepping. People with PD can improve protective stepping over the course of 1 day of perturbation practice. Improvements were generally similar to healthy adults, and were retained in both groups. Perturbation practice may represent a promising approach to improving protective postural responses in people with PD; however, additional research is needed to understand how to enhance generalization. PMID- 27193313 TI - Salt effects on the picosecond dynamics of lysozyme hydration water investigated by terahertz time-domain spectroscopy and an insight into the Hofmeister series for protein stability and solubility. AB - The addition of salts into protein aqueous solutions causes changes in protein solubility and stability, whose ability is known to be ordered in the Hofmeister series. We investigated the effects of Hofmeister salts on the picosecond dynamics of water around a lysozyme molecule using terahertz time-domain spectroscopy. The change in the absorption coefficient for 200 mg mL(-1) lysozyme aqueous solution by the addition of salts was found to depend on the salts used, whereas that for pure water was almost independent of salts. From the difference in the salt concentration dependence for various salts, it has been found that chaotropic anions make the dynamics of water around the lysozyme molecule slower, whereas kosmotropic anions make the dynamics faster. The ability of an anion to slow down the water dynamics was found to have the following order: SCN(-) > Cl( ) > H2PO4(-) > NO3(-) ~ SO4(2-). This result indicates that the effects of anions on the dynamics of water around the lysozyme molecule are the opposite of those for bulk water. This finding agrees with a prediction from a molecular model proposed by Collins [K. D. Collins, Methods, 2004, 34, 300]. The results presented here are compared with the results from preferential interaction studies and the results from sum frequency generation spectroscopy. These discussions have led to the conclusion that the picosecond dynamics of protein hydration water strongly contributes to protein stability, whereas electrostatic interactions between protein molecules contribute to protein solubility. PMID- 27193312 TI - CHI3L1 polymorphisms, cord blood YKL-40 levels and later asthma development. AB - BACKGROUND: Single nucleotide polymorphisms (SNPs) in chitinase 3-like 1 (CHI3L1), the gene encoding YKL-40, and increased serum YKL-40 levels are associated with severe forms of asthma. It has never been addressed whether SNPs in CHI3L1 and cord blood YKL-40 levels could already serve as potential biomarkers for milder forms of asthma. We assessed in an unselected population whether SNPs in CHI3L1 and cord blood YKL-40 levels at birth are associated with respiratory symptoms, lung function changes, asthma, and atopy. METHODS: In a prospective birth cohort of healthy term-born neonates (n = 260), we studied CHI3L1 polymorphisms, and measured cord blood YKL-40 levels by ELISA in (n = 170) infants. Lung function was performed at 5 weeks and 6 years. Respiratory health during the first year of life was assessed weekly by telephone interviews. Diagnosis of asthma and allergic sensitisation was assessed at 6 years (n = 142). RESULTS: The SNP rs10399805 was significantly associated with asthma at 6 years. The odds ratio for asthma was 4.5 (95 % CI 1.59-12.94) per T-allele. This finding was unchanged when adjusting for cord blood YKL-40 levels. There was no significant association for cord blood YKL-40 levels and asthma. SNPs in CHI3L1 and cord blood YKL-40 were not associated with lung function measurements at 5 weeks and 6 years, respiratory symptoms in the first year, and allergic sensitisation at 6 years. CONCLUSION: Genetic variation in CHI3L1 might be related to the development of milder forms of asthma. Larger studies are warranted to establish the role of YKL-40 in that pathway. PMID- 27193314 TI - Does supplementation of beef calves by creep feeding systems influence milk production and body condition of the dams? AB - The aim of this study was to evaluate the effects of beef calves' supplementation in creep feeding systems on milk yield, body weight (BW), and body condition score (BCS) of their dams on tropical pastures using a meta-analytical approach. The database was obtained from 11 experiments conducted between 2009 and 2014 in Brazil, totaling 485 observations (cows). The database consisted of 273 Nellore and 212 crossbred (7/8 Nellore * 1/8 Holstein) cows. All experiments were carried out in the suckling phase (from 3 to 8 months of age of calves) during the transition phase between rainy and dry seasons from February to June of different years. The data were analyzed by a meta-analytical approach using mixed models and taking into account random variation among experiments. Calves' supplementation (P >= 0.59) and the calves' sex (P >= 0.48) did not affect milk yield of cows. The average fat-corrected milk (FCM) yield was 6.71 and 6.83 kg/day for cows that had their calves supplemented and not supplemented, respectively. Differences were observed (P < 0.0001) for milk yield due to the genetic group where crossbred cows presented greater FCM yield (7.37 kg/day) compared with Nellore cows (6.17 kg/day). There was no effect of the calves' supplementation on BW change (P >= 0.11) and BCS change (P >= 0.23) of the cows. Therefore, it is concluded that supplementation of beef calves using creep feeding systems in tropical pastures does not affect milk yield, body weight, or body condition of their dams. PMID- 27193315 TI - Trends in percutaneous pericardial access during catheter ablation of ventricular arrhythmias: a single-center experience. AB - PURPOSE: Percutaneous pericardial access (EpiAcc) assists ventricular tachycardia/premature ventricular complex (VT/PVC) ablation by permitting epicardial mapping and ablation outside the vicinity of the coronary venous system. We sought to determine whether expanding indications and growing operator experience have led to increased rates of EpiAcc. METHODS: We reviewed the frequency of EpiAcc procedures performed during VT/PVC ablation between 2007 and 2014 to identify temporal trends in the procedure. RESULTS: There were 758 patients undergoing 880 VT/PVC ablation procedures (average 95 patients per year; 110 procedures per year) during the study period. EpiAcc for ablation was utilized in 170 patients (181 procedures). The average age at the time of EpiAcc was 55 +/- 16 years and 129 (76.0 %) patients were male. The rate of EpiAcc was 22.9 % in males and 15.4 % in females (P = 0.008). The absolute number of EpiAcc procedures increased from 2007 (6 procedures) to 2014 (27 procedures). Similarly, the proportion of patients undergoing EpiAcc increased from 8.6 % of procedures in 2007 to 24.5 % in 2014 (P < 0.0001). While EpiAcc use became more frequent, the rate of epicardial ablation among those who underwent EpiAcc remained stable (approximately 70 %). CONCLUSIONS: Percutaneous pericardial access has been used with increasing frequency as part of VT/PVC ablations without an increase in the rate of epicardial ablation. This growing utilization may lay the foundation for novel epicardial strategies as new technologies emerge. The frequency of percutaneous pericardial access in VT/PVC ablation appears to be greater in males, reasons for which are undefined. PMID- 27193316 TI - Outcomes after cryoballoon or radiofrequency ablation for persistent atrial fibrillation: a multicentric propensity-score matched study. AB - PURPOSE: Recent data show no benefit of additional ablation beyond pulmonary vein isolation (PVI) in persistent atrial fibrillation (AF). Evidence suggests that radiofrequency energy (RF) and cryoballoon (CRYO) have comparable efficacy for PVI. We aimed to assess the outcomes after a single catheter ablation procedure, comparing PVI using CRYO vs. RF ablation for PVI plus additional ablation in a cohort of patients with persistent AF. METHODS: In this prospective multicenter propensity score-matched comparison, 59 consecutive patients undergoing CRYO ablation of persistent AF were matched to 59 patients treated with RF from November 2010 to June 2012. RESULTS: During a mean follow-up of 15.6 +/- 11.5 months, 43.2 % of patients presented atrial arrhythmia relapse after a blanking period of 3 months, which was comparable between the two groups (40.7 % in CRYO vs. 45.8 % in RF, Log rank P = 0.14; HR = 0.67, 95 %CI 0.38-1.16, P = 0.15), despite the fact that 52.5 % of RF patients add additional complex fractionated atrial electrogram ablation, as well as left atrial linear ablation in over two thirds (roof line in 67.8 % and mitral isthmus in 32.2 %). On multivariate Cox regression, only AF duration in years (HR = 1.10, 95 %CI 1.01-1.10, P = 0.04) was a predictor of relapse. Patients undergoing RF ablation presented a numerically, but non-significantly, lower complication rate (6.8 vs 10.2 %, P = 0.51). CONCLUSION: In our multicenter experience, freedom from atrial arrhythmias was comparable among matched patients treated with CRYO and RF, despite non significant trends in favor of RF in terms of complications, at the cost of longer procedure times. PMID- 27193317 TI - Prefrontal and anterior cingulate cortex neurons encode attentional targets even when they do not apparently bias behavior. AB - Neurons in anterior cingulate and prefrontal cortex (ACC/PFC) carry information about behaviorally relevant target stimuli. This information is believed to affect behavior by exerting a top-down attentional bias on stimulus selection. However, attention information may not necessarily be a biasing signal but could be a corollary signal that is not directly related to ongoing behavioral success, or it could reflect the monitoring of targets similar to an eligibility trace useful for later attentional adjustment. To test this suggestion we quantified how attention information relates to behavioral success in neurons recorded in multiple subfields in macaque ACC/PFC during a cued attention task. We found that attention cues activated three separable neuronal groups that encoded spatial attention information but were differently linked to behavioral success. A first group encoded attention targets on correct and error trials. This group spread across ACC/PFC and represented targets transiently after cue onset, irrespective of behavior. A second group encoded attention targets on correct trials only, closely predicting behavior. These neurons were not only prevalent in lateral prefrontal but also in anterior cingulate cortex. A third group encoded target locations only on error trials. This group was evident in ACC and PFC and was activated in error trials "as if" attention was shifted to the target location but without evidence for such behavior. These results show that only a portion of neuronaly available information about attention targets biases behavior. We speculate that additionally a unique neural subnetwork encodes counterfactual attention information. PMID- 27193319 TI - On the nature of unintentional action: a study of force/moment drifts during multifinger tasks. AB - We explored the origins of unintentional changes in performance during accurate force production in isometric conditions seen after turning visual feedback off. The idea of control with referent spatial coordinates suggests that these phenomena could result from drifts of the referent coordinate for the effector. Subjects performed accurate force/moment production tasks by pressing with the fingers of a hand on force sensors. Turning the visual feedback off resulted in slow drifts of both total force and total moment to lower magnitudes of these variables; these drifts were more pronounced in the right hand of the right handed subjects. Drifts in individual finger forces could be in different direction; in particular, fingers that produced moments of force against the required total moment showed an increase in their forces. The force/moment drift was associated with a drop in the index of synergy stabilizing performance under visual feedback. The drifts in directions that changed performance (non-motor equivalent) and in directions that did not (motor equivalent) were of about the same magnitude. The results suggest that control with referent coordinates is associated with drifts of those referent coordinates toward the corresponding actual coordinates of the hand, a reflection of the natural tendency of physical systems to move toward a minimum of potential energy. The interaction between drifts of the hand referent coordinate and referent orientation leads to counterdirectional drifts in individual finger forces. The results also demonstrate that the sensory information used to create multifinger synergies is necessary for their presence over the task duration. PMID- 27193318 TI - Spontaneously active NaV1.5 sodium channels may underlie odor sensitivity. AB - The olfactory system is remarkably sensitive to airborne odor molecules, but precisely how very low odor concentrations bordering on just a few molecules per olfactory sensory neuron can trigger graded changes in firing is not clear. This report reexamines signaling in olfactory sensory neurons in light of the recent account of NaV1.5 sodium channel-mediated spontaneous firing. Using a model of spontaneous channel activity, the study shows how even submillivolt changes in membrane potential elicited by odor are expected to cause meaningful changes in NaV1.5-dependent firing. The results suggest that the random window currents of NaV1.5 channels may underpin not only spontaneous firing in olfactory sensory neurons but the cellular response to odor as well, thereby ensuring the robustness and sensitivity of signaling that is especially important for low odor concentrations. PMID- 27193321 TI - Subspace mapping of the three-dimensional spectral receptive field of macaque MT neurons. AB - Neurons in the middle temporal (MT) visual area are thought to represent the velocity (direction and speed) of motion. Previous studies suggest the importance of both excitation and suppression for creating velocity representation in MT; however, details of the organization of excitation and suppression at the MT stage are not understood fully. In this article, we examine how excitatory and suppressive inputs are pooled in individual MT neurons by measuring their receptive fields in a three-dimensional (3-D) spatiotemporal frequency domain. We recorded the activity of single MT neurons from anesthetized macaque monkeys. To achieve both quality and resolution of the receptive field estimations, we applied a subspace reverse correlation technique in which a stimulus sequence of superimposed multiple drifting gratings was cross-correlated with the spiking activity of neurons. Excitatory responses tended to be organized in a manner representing a specific velocity independent of the spatial pattern of the stimuli. Conversely, suppressive responses tended to be distributed broadly over the 3-D frequency domain, supporting a hypothesis of response normalization. Despite the nonspecific distributed profile, the total summed strength of suppression was comparable to that of excitation in many MT neurons. Furthermore, suppressive responses reduced the bandwidth of velocity tuning, indicating that suppression improves the reliability of velocity representation. Our results suggest that both well-organized excitatory inputs and broad suppressive inputs contribute significantly to the invariant and reliable representation of velocity in MT. PMID- 27193320 TI - Megamap: flexible representation of a large space embedded with nonspatial information by a hippocampal attractor network. AB - The problem of how the hippocampus encodes both spatial and nonspatial information at the cellular network level remains largely unresolved. Spatial memory is widely modeled through the theoretical framework of attractor networks, but standard computational models can only represent spaces that are much smaller than the natural habitat of an animal. We propose that hippocampal networks are built on a basic unit called a "megamap," or a cognitive attractor map in which place cells are flexibly recombined to represent a large space. Its inherent flexibility gives the megamap a huge representational capacity and enables the hippocampus to simultaneously represent multiple learned memories and naturally carry nonspatial information at no additional cost. On the other hand, the megamap is dynamically stable, because the underlying network of place cells robustly encodes any location in a large environment given a weak or incomplete input signal from the upstream entorhinal cortex. Our results suggest a general computational strategy by which a hippocampal network enjoys the stability of attractor dynamics without sacrificing the flexibility needed to represent a complex, changing world. PMID- 27193324 TI - Rethinking general anesthesia for cesarean section. PMID- 27193322 TI - Dopamine D1 receptor modulation of calcium channel currents in horizontal cells of mouse retina. AB - Horizontal cells form the first laterally interacting network of inhibitory interneurons in the retina. Dopamine released onto horizontal cells under photic and circadian control modulates horizontal cell function. Using isolated, identified horizontal cells from a connexin-57-iCre * ROSA26-tdTomato transgenic mouse line, we investigated dopaminergic modulation of calcium channel currents (ICa) with whole cell patch-clamp techniques. Dopamine (10 MUM) blocked 27% of steady-state ICa, an action blunted to 9% in the presence of the L-type Ca channel blocker verapamil (50 MUM). The dopamine type 1 receptor (D1R) agonist SKF38393 (20 MUM) inhibited ICa by 24%. The D1R antagonist SCH23390 (20 MUM) reduced dopamine and SKF38393 inhibition. Dopamine slowed ICa activation, blocking ICa by 38% early in a voltage step. Enhanced early inhibition of ICa was eliminated by applying voltage prepulses to +120 mV for 100 ms, increasing ICa by 31% and 11% for early and steady-state currents, respectively. Voltage-dependent facilitation of ICa and block of dopamine inhibition after preincubation with a Gbetagamma-blocking peptide suggested involvement of Gbetagamma proteins in the D1R-mediated modulation. When the G protein activator guanosine 5'-O-(3 thiotriphosphate) (GTPgammaS) was added intracellularly, ICa was smaller and showed the same slowed kinetics seen during D1R activation. With GTPgammaS in the pipette, additional block of ICa by dopamine was only 6%. Strong depolarizing voltage prepulses restored the GTPgammaS-reduced early ICa amplitude by 36% and steady-state ICa amplitude by 3%. These results suggest that dopaminergic inhibition of ICa via D1Rs is primarily mediated through the action of Gbetagamma proteins in horizontal cells. PMID- 27193326 TI - Changes in uncuffed endotracheal tube leak during laparoscopic inguinal herniorrhaphy in children. AB - The present study was conducted to investigate changes in uncuffed endotracheal tube (ETT) leak during laparoscopic surgery. The study included 31 patients aged between 1 and 6 years scheduled for elective laparoscopic inguinal herniorrhaphy. Inspiratory and expiratory tidal volumes (TVi and TVe) were measured during mechanical ventilation, and ETT leak was calculated using the formula-ETT leak = (TVi - TVe)/TVi * 100 (%), assessed at the following time-points-5 min after the start of mechanical ventilation (T1, baseline), just before the start of surgery (T2), 5 min after the induction of pneumoperitoneum with 15 degrees Trendelenburg tilt (T3), and at the end of surgery (T4). Additionally, leak pressure was assessed after successful tracheal intubation (T0, baseline) at T2, T3 and T4. Uncuffed ETT leak significantly decreased at T3 compared with T1 (baseline). Leak pressure significantly increased at T3 and T4 compared with T0 (baseline). Further studies are needed in order to determine whether the results are universal and associated with clinically significant outcomes. PMID- 27193327 TI - Unique Distribution of Benzodiazepine Receptors in the Brain during the First Two Years of Life. AB - BACKGROUND: 123I-iomazenil (IMZ) single-photon emission computed tomography (SPECT) is a tool for evaluating epileptic foci and brain damage. To apply the method to children, information regarding the age-specific expression of benzodiazepine receptors (BDZ-Rs) is required. Unfortunately, there is no information currently available for children <2 years of age. METHODS: We used IMZ SPECT once in infants aged 3-8 months and again at 2 years of age in order to describe the maturational changes in BDZ-R distribution. RESULTS: No neurological deficits were found in any of the infants at the first examination. The BDZ-Rs were more dominantly distributed in the occipital lobe than in the frontal lobe before the age of 2 years. The frontal-occipital gradients of the distribution were obvious in children <8 months of age. Magnetic resonance imaging showed a spreading of myelination toward the frontal lobes simultaneously with BDZ-R expression. CONCLUSION: Information regarding the alteration in the BDZ-R distribution pattern is useful when assessing infantile epilepsy and brain injury. The age-related pattern of BDZ-R distribution could correspond with myelination, cerebral blood flow, metabolism and behavioral development. PMID- 27193325 TI - Ciproxifan, an H3 receptor antagonist, improves short-term recognition memory impaired by isoflurane anesthesia. AB - BACKGROUND: Exposure to volatile anesthetics has been reported to cause temporary or sustained impairments in learning and memory in pre-clinical studies. The selective antagonists of the histamine H3 receptors (H3R) are considered to be a promising group of novel therapeutic agents for the treatment of cognitive disorders. The aim of this study was to evaluate the effect of H3R antagonist ciproxifan on isoflurane-induced deficits in an object recognition task. METHODS: Adult C57BL/6 J mice were exposed to isoflurane (1.3 %) or vehicle gas for 2 h. The object recognition tests were carried at 24 h or 7 days after exposure to anesthesia to exploit the tendency of mice to prefer exploring novel objects in an environment when a familiar object is also present. During the training phase, two identical objects were placed in two defined sites of the chamber. During the test phase, performed 1 or 24 h after the training phase, one of the objects was replaced by a new object with a different shape. The time spent exploring each object was recorded. RESULTS: A robust deficit in object recognition memory occurred 1 day after exposure to isoflurane anesthesia. Isoflurane-treated mice spent significantly less time exploring a novel object at 1 h but not at 24 h after the training phase. The deficit in short-term memory was reversed by the administration of ciproxifan 30 min before behavioral training. CONCLUSION: Isoflurane exposure induces reversible deficits in object recognition memory. Ciproxifan appears to be a potential therapeutic agent for improving post anesthesia cognitive memory performance. PMID- 27193323 TI - Inhibitory interneurons in visual cortical plasticity. AB - For proper maturation of the neocortex and acquisition of specific functions and skills, exposure to sensory stimuli is vital during critical periods of development when synaptic connectivity is highly malleable. To preserve reliable cortical processing, it is essential that these critical periods end after which learning becomes more conditional and active interaction with the environment becomes more important. How these age-dependent forms of plasticity are regulated has been studied extensively in the primary visual cortex. This has revealed that inhibitory innervation plays a crucial role and that a temporary decrease in inhibition is essential for plasticity to take place. Here, we discuss how different interneuron subsets regulate plasticity during different stages of cortical maturation. We propose a theory in which different interneuron subsets select the sources of neuronal input that undergo plasticity. PMID- 27193328 TI - Metformin-induced acute dystonia in a schizophrenic patient treated with sulpiride and clozapine. PMID- 27193329 TI - Altered localization and functionality of TAR DNA Binding Protein 43 (TDP-43) in niemann- pick disease type C. AB - Niemann-Pick type C (NPC) disease is a lysosomal storage disorder characterized by the occurrence of visceral and neurological symptoms. At present, the molecular mechanisms causing neurodegeneration in this disease are unknown. Here we report the altered expression and/or mislocalization of the TAR-DNA binding protein 43 (TDP-43) in both NPC mouse and in a human neuronal model of the disease. We also report the neuropathologic study of a NPC patient's brain, showing that while TDP-43 is below immunohistochemical detection in nuclei of cerebellar Purkinje cells, it has a predominant localization in the cytoplasm of these cells. From a functional point of view, the TDP-43 mislocalization, that occurs in a human experimental neuronal model system, is associated with specific alterations in TDP-43 controlled genes. Most interestingly, treatment with N Acetyl-cysteine (NAC) or beta-cyclodextrin (CD) can partially restore TDP-43 nuclear localization. Taken together, the results of these studies extend the role of TDP-43 beyond the Amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD)/Alzheimer disease (AD) spectrum. These findings may open novel research/therapeutic avenues for a better understanding of both NPC disease and the TDP-43 proteinopathy disease mechanism. PMID- 27193332 TI - Gold-catalyzed Hosomi-Sakurai type reaction for the total synthesis of herboxidiene. AB - Total synthesis of herboxidiene/GEX1A/TAN-1609 has been accomplished in the 22 longest linear sequences starting from 2-butyne-1,4-diol following our recently developed gold-catalyzed Hosomi-Sakurai type of reaction on lactols with allyltrimethyl silane and Stille cross coupling to assemble the advanced fragment. The synthesis of the C10-C19 fragment was accomplished by means of Sharpless epoxidation and asymmetric alkylation reactions starting from (R) methyl lactate. PMID- 27193330 TI - Early life overfeeding impairs spatial memory performance by reducing microglial sensitivity to learning. AB - BACKGROUND: Obesity can lead to cognitive dysfunction including poor performance in memory tasks. However, poor memory is not seen in all obese humans and takes several months to develop in animal models, indicating the adult brain is relatively resistant to obesity's cognitive effects. We have seen that, in the rat, overfeeding for as little as 3 weeks in early life leads to lasting obesity and microglial priming in the hypothalamus. Here we hypothesized that microglial hyper-sensitivity in the neonatally overfed rats extends beyond the hypothalamus into memory-associated brain regions, resulting in cognitive deficits. METHODS: We tested this idea by manipulating Wistar rat litter sizes to suckle pups in litters of 4 (overfed) or 12 (control). RESULTS: Neonatally overfed rats had microgliosis in the hippocampus after only 14 days overfeeding, and this persisted into adulthood. These changes were coupled with poor performance in radial arm maze and novel object recognition tests relative to controls. In controls, the experience of the radial arm maze reduced cell proliferation in the dentate gyrus and neuron numbers in the CA3. The learning task also suppressed microglial number and density in hippocampus and retrosplenial cortex. Neonatally overfed brains had impaired sensitivity to learning, with no neuronal or cell proliferative effects and less effective microglial suppression. CONCLUSIONS: Thus, early life overfeeding contributes to a long-term impairment in learning and memory with a likely role for microglia. These data may partially explain why some obese individuals display cognitive dysfunction and some do not, i.e. the early life dietary environment is likely to have a vital long-term contribution. PMID- 27193331 TI - A significant causal association between C-reactive protein levels and schizophrenia. AB - Many observational studies have shown elevated blood CRP levels in schizophrenia compared with controls, and one population-based prospective study has reported that elevated plasma CRP levels were associated with late- and very-late-onset schizophrenia. Furthermore, several clinical studies have reported the efficacy of anti-inflammatory drugs on the symptoms in patients with schizophrenia. However, whether elevated CRP levels are causally related to schizophrenia is not still established because of confounding factors and reverse causality. In the present study, we demonstrated that serum CRP levels were significantly higher in patients with schizophrenia than in the controls by conducting a case-control study and a meta-analysis of case-control studies between schizophrenia and serum CRP levels. Furthermore, we provided evidence for a causal association between elevated CRP levels and increased schizophrenia risk by conducting a Mendelian randomization analysis. Our findings suggest that elevated CRP itself may be a causal risk factor for schizophrenia. PMID- 27193334 TI - Facing forward after Ebola: questions for the next director general of the World Health Organization. PMID- 27193335 TI - [Rheumatology - Integration into student training (RISA) : Current structure of clinical rheumatology in German universities (RISA III)]. AB - The German Society of Rheumatology and the Committee for Student Training investigated what effects the structures in university medicine have on student teaching. In February 2014 a questionnaire was sent to the teaching staff and Deans of each of the 37 medical faculties. Of the locations seven were classified as being independent rheumatological university hospitals and nine universities had a W2/W3/C3 grade professor as head of a department of clinical rheumatology but answerable to superiors. In the 37 faculties in Germany the proportion of lecture hours, the proportion of obligatory lecture hours, the number of hours for practical exercises and the number of hours for bedside teaching were distributed very differently and as a rule higher in universities with academic freedom. Not all medical faculties have obligatory teaching in the field of clinical rheumatology. On average medical students see five patients with rheumatological symptoms during their studies. In summary, over the past years it has not been possible to successfully utilize the great importance of rheumatology for society and the innovation potential of this discipline in order to improve the integration of clinical rheumatology into universities. PMID- 27193336 TI - [Severe therapy refractive osteoporosis : A rare differential diagnosis]. AB - Systemic mastocytosis is defined as a clonal increase of mast cells. We report on four patients with severe osteoporosis and histologically confirmed systemic mastocytosis. In spite of antiresorptive therapy the patients developed further vertebral fractures and suffered from ostealgia. Systemic mastocytosis is an important differential diagnosis in patients with therapy refractive and unexplained osteoporosis. Skin involvement (urticaria pigmentosa) is a rare occurrence and in most cases an isolated involvement of bone marrow is present. Determination of serum tryptase can provide indications for systemic mastocytosis but the diagnosis is only confirmed by bone marrow biopsy. There is a high risk of vertebral fractures and patients should be treated in specialized centers. Zoledronic acid can be a therapeutic option for indolent osteoporosis associated with systemic mastocytosis. PMID- 27193333 TI - Phenotypic dynamics of microglial and monocyte-derived cells in glioblastoma bearing mice. AB - Inflammatory cells, an integral component of tumor evolution, are present in Glioblastomas multiforme (GBM). To address the cellular basis and dynamics of the inflammatory microenvironment in GBM, we established an orthotopic syngenic model by grafting GL261-DsRed cells in immunocompetent transgenic LysM-EGFP//CD11c-EYFP reporter mice. We combined dynamic spectral two-photon imaging with multiparametric cytometry and multicolor immunostaining to characterize spatio temporal distribution, morphology and activity of microglia and blood-derived infiltrating myeloid cells in live mice. Early stages of tumor development were dominated by microglial EYFP(+) cells invading the tumor, followed by massive recruitment of circulating LysM-EGFP(+) cells. Fluorescent invading cells were conventional XCR1(+) and monocyte-derived dendritic cells distributed in subpopulations of different maturation stages, located in different areas relative to the tumor core. The lethal stage of the disease was characterized by the progressive accumulation of EGFP(+)/EYFP(+) monocyte-derived dendritic cells. This local phenotypic regulation of monocyte subtypes marked a transition in the immune response. PMID- 27193337 TI - Electrochemical nanostructured ZnO biosensor for ultrasensitive detection of cardiac troponin-T. AB - AIM: Vertically oriented zinc oxide nanostructures based disposable diagnostic biosensor for detecting and quantifying levels of cardiac troponin-T from human serum has been developed. MATERIALS & METHODS: The biosensors were designed by integrating hydrothermally grown zinc oxide nanostructures on glass and printed circuit board platforms, resulting in the generation of high-density nanostructure arrays with nanotextured zinc oxide based electrodes. The size, density and surface terminations of the nanostructures were leveraged toward achieving surface confinement of the target cTnT molecules on to the nanostructures. A combination of AC and DC spectroscopy was used to characterize the biosensor response to cTnT. RESULTS & CONCLUSION: LOD of 0.1 pg/ml in human serum was achieved. PMID- 27193338 TI - Remarkable points for cardiovascular studies in fibromyalgia syndrome management. PMID- 27193340 TI - Muscle regeneration after sepsis. AB - Severe critical illness is often complicated by intensive care unit-acquired weakness (ICU-AW), which is associated with increased ICU and post-ICU mortality, delayed weaning from mechanical ventilation and long-term functional disability. Several mechanisms have been implicated in the pathophysiology of ICU-AW, but muscle regeneration has not been investigated to any extent in this context, even though its involvement is suggested by the protracted functional consequences of ICU-AW. Recent data suggest that muscle regeneration could be impaired after sepsis, and that mesenchymal stem cell treatment could improve the post-injury muscle recovery. PMID- 27193339 TI - Distinct white-matter aberrations in 22q11.2 deletion syndrome and patients at ultra-high risk for psychosis. AB - BACKGROUND: Patients with a deletion at chromosome 22q11.2 (22q11DS) have 30% lifetime risk of developing a psychosis. People fulfilling clinical criteria for ultra-high risk (UHR) for psychosis have 30% risk of developing a psychosis within 2 years. Both high-risk groups show white-matter (WM) abnormalities in microstructure and volume compared to healthy controls (HC), which have been related to psychotic symptoms. Comparisons of WM pathology between these two groups may specify WM markers related to genetic and clinical risk factors. METHOD: Fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) were assessed using diffusion tensor magnetic resonance imaging (MRI), and WM volume with structural MRI, in 23 UHR patients, 21 22q11DS patients, and 33 HC. RESULTS: Compared to UHR patients 22q11DS patients had (1) lower AD and RD in corpus callosum (CC), cortical fasciculi, and anterior thalamic radiation (ATR), (2) higher FA in CC and ATR, and (3) lower occipital and superior temporal gyrus WM volume. Compared to HC, 22q11DS patients had (1) lower AD and RD throughout cortical fasciculi and (2) higher FA in ATR, CC and inferior fronto-occipital fasciculus. Compared to HC, UHR patients had (1) higher mean MD, RD, and AD in CC, ATR and cortical fasciculi, (2) no differences in FA. CONCLUSIONS: UHR and 22q11DS patients share a susceptibility for developing psychosis yet were characterized by distinct patterns of WM alterations relative to HC. While UHR patients were typified by signs suggestive of aberrant myelination, 22q11DS subjects showed signs suggestive of lower axonal integrity. PMID- 27193341 TI - Ecosystemic, climatic and temporal differences in oribatid communities (Acari: Oribatida) from forest soils. AB - Oribatid mite communities from 18 natural autochthonous forest soils in the Basque Country, belonging to five forest types, distributed along an ombrothermic gradient of five climatic regions were broadly studied. Forest type and climatic region together (45 % of the total variability) were important factors influencing the oribatid community. The local scale variable (forest type, 28 %) was about as determinant a factor as the regional scale (climatic region, 26 %), though together they accounted for just 9 %. By contrast, the influence of spatial distribution (geography) was not significant by itself but played an important role as a co-variable. Differences in community indices were detected only for species abundances, with holm oak showing the highest oribatid density and beech the lowest. The effect of the passage of time on oribatid communities was also analyzed by comparing recent communities to those of 19-26 years ago in the same forests. The community indices are influenced by the course of time when separate periods of time are compared. Although the recently studied forests apparently show the same conservational conditions as those studied in the past, they are less diverse. PMID- 27193342 TI - New-Onset Scleral Icterus in a School-Aged Female. PMID- 27193343 TI - [Contested fields in neurology]. PMID- 27193344 TI - Single-channel EEG sleep stage classification based on a streamlined set of statistical features in wavelet domain. AB - The main objective of this study was to enhance the performance of sleep stage classification using single-channel electroencephalograms (EEGs), which are highly desirable for many emerging technologies, such as telemedicine and home care. The proposed method consists of decomposing EEGs by a discrete wavelet transform and computing the kurtosis, skewness and variance of its coefficients at selected levels. A random forest predictor is trained to classify each epoch into one of the Rechtschaffen and Kales' stages. By performing a comprehensive set of tests on 106,376 epochs available from the Physionet public database, it is demonstrated that the use of these three statistical moments has enhanced performance when compared to their application in the time domain. Furthermore, the chosen set of features has the advantage of exhibiting a stable classification performance for all scoring systems, i.e., from 2- to 6-state sleep stages. The stability of the feature set is confirmed with ReliefF tests which show a performance reduction when any individual feature is removed, suggesting that this group of feature cannot be further reduced. The accuracies and kappa coefficients yield higher than 90 % and 0.8, respectively, for all of the 2- to 6-state sleep stage classification cases. PMID- 27193345 TI - Serum brain-derived neurotrophic factor (BDNF) concentrations in pregnant women with post-traumatic stress disorder and comorbid depression. AB - There is accumulating evidence for the role of brain-derived neurotrophic factor (BDNF) in the pathophysiology of depression. However, the role of BDNF in the pathophysiology of post-traumatic stress disorder (PTSD) remains controversial, and no study has assessed BDNF concentrations among pregnant women with PTSD. We examined early-pregnancy BDNF concentrations among women with PTSD with and without depression. A total of 2928 women attending prenatal care clinics in Lima, Peru, were recruited. Antepartum PTSD and depression were evaluated using PTSD Checklist-Civilian Version (PCL-C) and Patient Health Questionnaire-9 (PHQ 9) scales, respectively. BDNF concentrations were measured in a subset of the cohort (N = 944) using a competitive enzyme-linked immunosorbent assay (ELISA). Logistic regression procedures were used to estimate odds ratios (OR) and 95 % confidence intervals (95 % CI). Antepartum PTSD (37.4 %) and depression (27.6 %) were prevalent in this cohort of low-income pregnant Peruvian women. Approximately 19.9 % of participants had comorbid PTSD-depression. Median serum BDNF concentrations were lower among women with comorbid PTSD-depression as compared with women without either condition (median [interquartile range], 20.44 [16.97-24.30] vs. 21.35 [17.33-26.01] ng/ml; P = 0.06). Compared to the referent group (those without PTSD and depression), women with comorbid PTSD-depression were 1.52-fold more likely to have low (<25.38 ng/ml) BDNF concentrations (OR = 1.52; 95 % CI 1.00-2.31). We observed no evidence of reduced BDNF concentrations among women with isolated PTSD. BDNF concentrations in early pregnancy were only minimally and non-significantly reduced among women with antepartum PTSD. Reductions in BDNF concentrations were more pronounced among women with comorbid PTSD-depression. PMID- 27193346 TI - Persistence and drug tolerance in pathogenic yeast. AB - In this review, we briefly summarize the current understanding of how fungal pathogens can persist antifungal treatment without heritable resistance mutations by forming tolerant persister cells. Fungal infections tolerant to antifungal treatment have become a major medical problem. One mechanism leading to drug recalcitrance is the formation of antifungal persister cells. These cells have wild-type genotype with the ability to survive exposure to antifungal agents due to changed membrane composition, upregulated stress response, and enhanced cell wall integrity. Knowledge of the mechanisms regulating entry and exit of the persister phenotype is limited, but it has recently been shown that the inhibition of the growth regulating TORC1 pathway induces fungal persistence. The phenotypic properties of persister cells and the involvement of the TORC1 pathway indicate that persister cells are quiescent in G0 of the cell cycle. This knowledge leads us to suggest that the identified shared drug-tolerance mechanisms of persister and quiescent cells may serve as a foundation for developing novel treatment strategies that are independent of growth mode against systemic fungal infections. PMID- 27193347 TI - ["Choosing wisely" in infectious diseases : Overuse of antibiotics - too few vaccinations]. AB - The "choosing wisely" recommendations of the German Society of Internal Medicine (DGIM) and its specialist societies address diagnostic and therapeutic procedures, which are of particular medical importance but applied too often or too rarely in clinical practice. The aim is to further improve treatment of patients. Important topics of overuse and insufficient treatment related to the diagnostics, therapy, prevention and exclusion of infectious diseases could be identified. These topics not only play an important role in the discipline of infectious diseases but are also relevant for other internal medical disciplines. These topics related to infectious diseases have also been integrated into the recommendations of the German Society of Gastroenterology, Digestive and Metabolic Diseases as well as the German Societies for Internal Intensive Care and Emergency Medicine, for Pneumology, for Nephrology and for Rheumatology. The pivotal issues of the recommendations are the inappropriate use of antibiotics and insufficient vaccination rates. PMID- 27193348 TI - First molecular identification of Dirofilaria spp. (Onchocercidae) in mosquitoes from Serbia. AB - Dirofilariosis is a common and widespread veterinary health issue in several European countries with notable zoonotic potential. The causative agents are Dirofilaria immitis and Dirofilaria repens nematoda species which are transmitted by different mosquito vectors. Similar to other mosquito-borne infections, the knowledge about mosquito species involved in disease transmission is crucial for the complex understanding of local transmission cycles. Since there is no available data on mosquito species, potentially involved in disease transmission from Serbia, 6369 female mosquito individuals were retrospectively tested for Dirofilaria nematodes, collected from 13 localities in Vojvodina province, Serbia, in 2013. Altogether, 8.33 % of tested pools showed positivity, composed of five mosquito species, mainly, Culex pipiens and Aedes vexans. D. immitis and D. repens were both detected from multiple localities, during the whole period of mosquito breeding season, which provides the first data on local transmission characteristics regarding mosquitoes from the Balkans. PMID- 27193349 TI - Jointed toxicity of TiO2 NPs and Cd to rice seedlings: NPs alleviated Cd toxicity and Cd promoted NPs uptake. AB - Previous studies have reported that nanoparticles (NPs) and heavy metals are toxic to the environment. However, the jointed toxicity is not yet well understood. This study was aimed to investigate the combined toxicity of TiO2 NPs and the heavy metal cadmium (Cd) to plants. Rice (Oryzasativa L.) was selected as the target plant. The rice seedlings were randomly separated into 12 groups and treated with CdCl2 (0, 10 and 20 mg/L) and TiO2 NPs (0, 10, 100 and 1000 mg/L). The plant height, biomass and root length indicated significant toxicity of Cd to the growth, but TiO2 NPs exhibited the potential ability to alleviate the Cd toxicity. Transmission electron microscopy (TEM) and energy dispersive spectrometer (EDS) confirmed the existence of TiO2 NPs in plants. Elemental analysis of Ti and Cd suggested that the presences of Cd significantly decreased the Ti accumulation in the rice roots in the co-exposure treatments. Interestingly, TiO2 NPs could lower the Cd uptake and distribution in rice roots and leaves. The results of antioxidant enzyme activity, lipid peroxide as well as phytohormones varied in the different treatments. Comparing with the Cd alone treatment, the net photosynthetic rate and chlorophyll content were significantly increased in the co-exposure treatments, suggesting that TiO2 NPs could tremendously reduce the Cd toxicity. PMID- 27193350 TI - Small ruminant lentiviral Vif proteins commonly utilize cyclophilin A, an evolutionarily and structurally conserved protein, to degrade ovine and caprine APOBEC3 proteins. AB - Mammals have co-evolved with retroviruses, including lentiviruses, over a long period. Evidence supporting this contention is that viral infectivity factor (Vif) encoded by lentiviruses antagonizes the anti-viral action of cellular apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3 (APOBEC3) of the host. To orchestrate E3 ubiquitin ligase complex for APOBEC3 degradation, Vifs utilize mammalian proteins such as core-binding factor beta (CBFB; for primate lentiviruses) or cyclophilin A (CYPA; for Maedi-Visna virus [MVV]). However, the co-evolutionary relationship between lentiviral Vif and the mammalian proteins associated with Vif-mediated APOBEC3 degradation is poorly understood. Moreover, it is unclear whether Vif proteins of small ruminant lentiviruses (SRLVs), including MVV and caprine arthritis encephalitis virus (CAEV), commonly utilize CYPA to degrade the APOBEC3 of their hosts. In this study, molecular phylogenetic and protein homology modeling revealed that Vif co factors are evolutionarily and structurally conserved. It was also found that not only MVV but also CAEV Vifs degrade APOBEC3 of both sheep and goats and that CAEV Vifs interact with CYPA. These findings suggest that lentiviral Vifs chose evolutionarily and structurally stable proteins as their partners (e.g., CBFB or CYPA) for APOBEC3 degradation and, particularly, that SRLV Vifs evolved to utilize CYPA as their co-factor in degradation of ovine and caprine APOBEC3. PMID- 27193352 TI - Nitrogen-Rich Manganese Oxynitrides with Enhanced Catalytic Activity in the Oxygen Reduction Reaction. AB - The catalytic activity of manganese oxynitrides in the oxygen reduction reaction (ORR) was investigated in alkaline solutions to clarify the effect of the incorporated nitrogen atoms on the ORR activity. These oxynitrides, with rock salt-like structures with different nitrogen contents, were synthesized by reacting MnO, Mn2 O3 , or MnO2 with molten NaNH2 at 240-280 degrees C. The anion contents and the Mn valence states were determined by combustion analysis, powder X-ray diffraction, and X-ray absorption near-edge structure analysis. An increase in the nitrogen content of rock-salt-based manganese oxynitrides increases the valence of the manganese ions and reinforces the catalytic activity for the ORR in 1 m KOH solution. Nearly single-electron occupancy of the antibonding eg states and highly covalent Mn-N bonding thus enhance the ORR activity of nitrogen rich manganese oxynitrides. PMID- 27193351 TI - Prospective assessment of serum periostin as a biomarker for diagnosis and monitoring of eosinophilic oesophagitis. AB - BACKGROUND: Periostin is highly expressed in eosinophilic oesophagitis (EoE), but has not been extensively studied as a non-invasive biomarker. AIM: To assess whether serum periostin distinguished EoE from controls at baseline, had utility for monitoring treatment response, or was associated with IL-13 levels. METHODS: This was a sub-analysis of a prospective cohort study of adults undergoing out patient upper endoscopy. Incident cases of EoE were diagnosed per consensus guidelines. Controls were subjects with either GERD or dysphagia without EoE. EoE patients were treated with swallowed/topical steroids and had repeat endoscopy/biopsy. Serum periostin levels for cases and controls were compared at baseline, and pre/post-treatment levels were compared for cases. Serum IL-13 and tissue expression of periostin were also assessed. RESULTS: A total of 61 incident EoE cases and 87 controls were analysed. Despite a marked increase in tissue periostin expression in cases, the median baseline serum periostin level was only slightly higher in cases than controls (22.1 ng/mL vs. 20.7; P = 0.04); there was no change in post-treatment levels. There was also no difference in serum periostin for cases by histologic response or atopic status. There was a strong trend towards higher serum IL-13 levels in cases in the highest periostin quartile (57.1 pg/mL vs. 2.6; P = 0.07). CONCLUSIONS: Serum periostin levels were similar in cases and controls, and there were no changes post-treatment. Given elevated IL-13 levels in the EoE patients with the highest periostin levels, future studies could explore periostin as a biomarker in EoE, perhaps in the setting of anti-IL-13 therapy. PMID- 27193353 TI - Design of alpha-Fe2O3 nanorods functionalized tubular NiO nanostructure for discriminating toluene molecules. AB - A novel tubular NiO nanostructure was synthesized by a facile and low-cost hydrothermal strategy and then further functionalized by decorating alpha-Fe2O3 nanorods. The images of electron microscopy indicated that the alpha-Fe2O3 nanorods were assembled epitaxially on the surfaces of NiO nanotubes to form alpha-Fe2O3/NiO nanotubes. As a proof-of-concept demonstration of the function, gas sensing devices were fabricated from as-prepared alpha-Fe2O3/NiO nanotubes, and showed enhanced gas response and excellent selectivity toward toluene, giving a response of 8.8 to 5 ppm target gas, which was about 7.8 times higher than that of pure NiO nanotubes at 275 degrees C. The improved gas sensing performance of alpha-Fe2O3/NiO nanotubes could be attributed to the unique tubular morphology features, p-n heterojunctions and the synergetic behavior of alpha-Fe2O3 and NiO. PMID- 27193355 TI - Green Tea Versus Traditional Korean Teas: Antibacterial/Antifungal or Both? AB - The feasibility of utilizing the antimicrobial activity of naturally available teas was studied. Eleven teas including 2 green teas and 9 other traditional Korean mixed teas were tested for their antimicrobial properties. Antibacterial and antifungal properties were assessed. The results showed that green teas possessed significant antifungal and antibacterial properties, while most of the mixed teas showed some amount of antifungal activity and almost insignificant antibacterial properties. Confocal microscopic imaging revealed mycelial damage as well as attack on sporophores rather than spores/spore germination to be the reason behind the antifungal activity. EGCG was identified as the crucial catechin for antimicrobial activity. The study confirmed that green tea had a clear edge over the traditional mixed teas when it comes to antimicrobial activity. PMID- 27193354 TI - The WRKY Transcription Factor Family in Citrus: Valuable and Useful Candidate Genes for Citrus Breeding. AB - WRKY transcription factors belong to a large family of plant transcriptional regulators whose members have been reported to be involved in a wide range of biological roles including plant development, adaptation to environmental constraints and response to several diseases. However, little or poor information is available about WRKY's in Citrus. The recent release of completely assembled genomes sequences of Citrus sinensis and Citrus clementina and the availability of ESTs sequences from other citrus species allowed us to perform a genome survey for Citrus WRKY proteins. In the present study, we identified 100 WRKY members from C. sinensis (51), C. clementina (48) and Citrus unshiu (1), and analyzed their chromosomal distribution, gene structure, gene duplication, syntenic relation and phylogenetic analysis. A phylogenetic tree of 100 Citrus WRKY sequences with their orthologs from Arabidopsis has distinguished seven groups. The CsWRKY genes were distributed across all ten sweet orange chromosomes. A comprehensive approach and an integrative analysis of Citrus WRKY gene expression revealed variable profiles of expression within tissues and stress conditions indicating functional diversification. Thus, candidate Citrus WRKY genes have been proposed as potentially involved in fruit acidification, essential oil biosynthesis and abiotic/biotic stress tolerance. Our results provided essential prerequisites for further WRKY genes cloning and functional analysis with an aim of citrus crop improvement. PMID- 27193356 TI - The Influence of Pole Length on Performance, O2 Cost, and Kinematics in Double Poling. AB - PURPOSE: In the double-poling (DP) cross-country-skiing technique, propulsive forces are transferred solely through the poles. The aim of the current study was to investigate how pole length influences DP performance, O2 cost, and kinematics during treadmill roller skiing. METHODS: Nine male competitive cross-country skiers (24 +/- 3 y, 180 +/- 5 cm, 72 +/- 5 kg, VO2max running 76 +/- 6 mL . kg-1 . min-1) completed 2 identical test protocols using self-selected (84% +/- 1% of body height) and long poles (self-selected + 7.5 cm; 88% +/- 1% of body height) in a counterbalanced fashion. Each test protocol included a 5-min warm-up (2.5 m/s; 2.5 degrees ) and three 5-min submaximal sessions (3.0, 3.5, and 4.0 m/s; 2.5 degrees ) for assessment of O2 cost, followed by a selfpaced 1000-m time trial (~3 min, >5.0 m/s; 2.5 degrees ). Temporal patterns and kinematics were assessed using accelerometers and 2D video. RESULTS: Long poles reduced 1000-m time (mean +/- 90% confidence interval; -1.0% +/- 0.7%, P = .054) and submaximal O2 cost (-2.7% +/- 1.0%, P = .002) compared with self-selected poles. The center of-mass (CoM) vertical range of displacement tended to be smaller for long than for self-selected poles (23.3 +/- 3.0 vs 24.3 +/- 3.0 cm, P = .07). Cycle and reposition time did not differ between pole lengths at any speeds tested, whereas poling time tended to be shorter for self-selected than for long poles at the lower speeds (<=3.5 m/s, P <= .10) but not at the higher speeds (>=4.0 m/s, P >= .23). CONCLUSIONS: DP 1000-m time, submaximal O2 cost, and CoM vertical range of displacement were reduced in competitive cross-country skiers using poles 7.5 cm longer than self-selected ones. PMID- 27193357 TI - Trends in cancer survivors' experience of patient-centered communication: results from the Health Information National Trends Survey (HINTS). AB - PURPOSE: Two Institute of Medicine reports almost a decade apart suggest that cancer survivors often feel "lost in transition" and experience suboptimal quality of care. The six core functions of patient-centered communication: managing uncertainty, responding to emotions, making decisions, fostering healing relationships, enabling self-management, and exchanging information, represent a central aspect of survivors' care experience that has not been systematically investigated. METHODS: Nationally representative data from four administrations of the Health Information National Trends Survey (HINTS) was merged with combined replicate weights using the jackknife replication method. Linear and logistic regression models were used to assess (1) characteristics of cancer survivors (N = 1794) who report suboptimal patient-centered communication and (2) whether survivors' patient-centered communication experience changed from 2007 to 2013. RESULTS: One third to one half of survivors report suboptimal patient-centered communication, particularly on core functions of providers helping manage uncertainty (48 %) and responding to emotions (49 %). In a fully adjusted linear regression model, survivors with more education (Wald F = 2.84, p = .04), without a usual source of care (Wald F = 11.59, p < .001), and in poorer health (Wald F = 9.08, p < .001) were more likely to report less patient-centered communication. Although ratings of patient-centered communication improved over time (p trend = .04), this trend did not remain significant in fully adjusted models. CONCLUSIONS: Despite increased attention to survivorship, many survivors continue to report suboptimal communication with their health care providers. IMPLICATIONS FOR CANCER SURVIVORS: Survivorship communication should include managing uncertainty about future risk and address survivors' emotional needs. Efforts to improve patient-centered communication should focus on survivors without a usual source of care and in poorer health. PMID- 27193358 TI - Disability Rating Scales in Parkinson's Disease: Critique and Recommendations. AB - INTRODUCTION: PD is associated with impairments that progress over time to disability. A large number of disability scales exist with little information on the best choice in PD. METHODS: Following methodology adopted by the International Parkinson and Movement Disorder Society Task Force, a review of disability scales used in PD was completed. Based on prespecified criteria, the review categorized scales into: "Recommended"; "Recommended with Further Validation in PD Required" when well-validated scales have not been specifically tested for clinimetric properties in PD; "Suggested"; and "Listed." RESULTS: Twenty-nine disability instruments were identified with nine scales fulfilling criteria for "Recommended" and 7 "Recommended with Further Validation in PD Required." Eight scales are "Suggested" and five scales are "Listed" for use in PD. The nine Recommended scales (Functional Status Questionnaire, Lawton-Brody Activities of Daily Living, Nottingham Activities of Daily Living, Schwab and England Activities of Daily Living, Self-Assessment PD Disability, Short Parkinson's Evaluation Scale/Scales for Outcomes in PD, Unified PD Rating Scale II: Activities of Daily Living, Movement Disorders Society UPDRS Motor Experiences of Daily Living, PROMIS(r) and Neuro-QoL Physical Function), and the seven Recommended with Further Validation in PD Required are reviewed. CONCLUSION: Many disability measures are available and recommended for application in PD. The Task Force does not recommend the development of a new scale. Selection of the most appropriate instrument for a particular objective requires consideration of the characteristics of each scale and the goals of the assessment. (c) 2016 International Parkinson and Movement Disorder Society. PMID- 27193360 TI - Some Unusual Neuropsychological Syndromes: Somatoparaphrenia, Akinetopsia, Reduplicative Paramnesia, Autotopagnosia. AB - Some unusual neuropsychological syndromes are rarely reported in the neuropsychological literature. This paper presents a review of four of these unusual clinical syndromes: (1) somatoparaphrenia (delusional belief in which a patient states that the limb contralateral to a brain pathology, does not belong to him/her); (2) akinetopsia (cortical syndrome in which patient losses the ability to perceive visual motion); (3) reduplicative paramnesia (believe that a familiar place, person, object, or body part has been duplicated); and (4) autotopagnosia (disturbance of body schema involving the loss of ability to localize, recognize, or identify the specific parts of one's body). It is concluded that regardless of their rarity, it is fundamental to take them into consideration in order to understand how the brain organizes cognition; their understanding is also crucial in the clinical analysis of patients with brain pathologies. PMID- 27193359 TI - Epitrochlear cat scratch disease: unique imaging features allowing differentiation from other soft tissue masses of the medial arm. AB - OBJECTIVE: Evaluate anatomic and imaging features of epitrochlear regional adenopathy secondary to cat scratch disease (CSD) to assist differentiation of CSD from other soft tissue masses at the elbow. MATERIALS AND METHODS: Retrospective review of 24 confirmed cases of CSD. Patient demographics, clinical presentation and radiographic (R; n = 10), CT (n = 3), ultrasound (US; n = 5), and MR (n = 21) images were reviewed. Lesion location, size, number of masses, and intrinsic characteristics on R/CT/US/MR and presence of soft tissue inflammatory changes or adjacent bone or joint involvement were established through the consensus interpretation by four musculoskeletal radiologists. RESULTS: The average patient age was 18.6 years. Mass location was anterior and superficial to the medial intermuscular septum (100 %) with the masses posterior or posteromedial to the basilic vein (92 %). Three or fewer lymph nodes were involved in 92 %. Masses were noncalcified with adjacent inflammatory change (R = 90 %, CT = 100 %). US showed hypoechoic soft tissue echogenicity masses with defined to minimally irregular margins (80 %) and preserved central hilar hypervascularity on Doppler (100 % of cases). On MR, masses were T1 isointense (62 %), T2 isointense (54 %), intermediate signal on T2 images with fat suppression (55 %), and had perilesional inflammatory changes (95 %), perilesional fluid collections (38 %), adjacent muscle edema (81 %), hyperintense cental hilar vascular enhancement (65 %) and occasional preserved central hilar fat (14 %). CONCLUSION: Cat scratch disease is suggested by the characteristic location of a medial epitrochlear mass superficial to the brachial fascia and posterior to the basilic vein with surrounding inflammatory changes and preservation of hilar vascular architecture, hilar enhancement and occasional hilar fat. PMID- 27193361 TI - Verbal Memory Abilities in Severe Childhood Psychiatric Disorders and the Influence of Attention and Executive Functions. AB - Despite prior adult research regarding the influence of executive functions on memory performance, there has been inconsistent prior research on the role of executive functions on memory performance in children, particularly those children with severe psychiatric disorders. A medical chart review was conducted for 76 children (ages 6-12 years) who received a neuropsychological evaluation during children's psychiatric inpatient program hospitalization. A series of hierarchical regression analyses investigated the role of attention/executive and non-executive functions in verbal memory performance (immediate recall, delayed recall, and delayed recognition). Demographic and verbal measures were entered into blocks 1 and 2 for all analyses, followed by attention and executive functions (i.e., attention span, sustained attention, verbal fluency, cognitive flexibility, inhibitory control, and planning/organization). Nearly 15% of the participants displayed memory impairment. Results of regression analyses indicated attention/executive dysfunction severity predicted overall memory performance. Attention span predicted performance on all three memory conditions. Planning/organization accounted for unique variance in immediate recall condition while inhibitory control accounted for unique variance in delayed recall condition. These results indicate that verbal memory problems frequently occur in severe childhood psychiatric disorders. Further, planning/organization deficits may influence immediate recall, while inhibitory control deficits may influence delayed recall. Alternatively, delayed recognition memory may be the most resistant to the negative influence of executive deficits on verbal memory performance in childhood psychiatric disorders. PMID- 27193362 TI - Prevalence of below-criterion Reliable Digit Span scores in a clinical sample of older adults. AB - OBJECTIVE: The Reliable Digit Span (RDS) is a well-validated embedded indicator of performance validity. An RDS score of <=7 is commonly referenced as indicative of invalid performance; however, few studies have examined the classification accuracy of the RDS among individuals suspected for dementia. The current study evaluated performance of the RDS in a clinical sample of 934 non-litigating individuals presenting to an outpatient memory disorders clinic for assessment of dementia. METHOD: The RDS was calculated for each participant in the context of a comprehensive neuropsychological assessment completed as part of routine clinical care. Score distributions were examined to establish the base rate of below criterion performance for RDS cutoffs of <=7, <=6, and <=5. One-way ANOVA was used to compare performance on a cognitive screening measure and informant reports of functional independence of those falling below and above cutoffs. RESULTS: A cutoff score of <=7 resulted in a high prevalence of below-criterion performance (29.7%), though an RDS of <=6 was associated with fewer below criterion scores (12.8%) and prevalence of an RDS of <=5 was infrequent (4.3%). Those scoring below cutoffs performed worse on cognitive measures compared with those falling above cutoffs. CONCLUSIONS: Using the RDS as a measure of performance validity among individuals presenting with a possibility of dementia increases the risk of misinterpreting genuine cognitive impairment as invalid performance when higher cutoffs are used; lower cutoffs may be useful when interpreted in conjunction with other measures of performance validity. PMID- 27193363 TI - Mild Cognitive Impairment in Late Middle Age in the Wisconsin Registry for Alzheimer's Prevention Study: Prevalence and Characteristics Using Robust and Standard Neuropsychological Normative Data. AB - OBJECTIVE: Detecting cognitive decline in presymptomatic Alzheimer's disease (AD) and early mild cognitive impairment (MCI) is challenging, but important for treatments targeting AD-related neurodegeneration. The current study aimed to investigate the utility and performance of internally developed robust norms and standard norms in identifying cognitive impairment in late middle-age (baseline age range = 36-68; M = 54). METHOD: Robust norms were developed for neuropsychological measures based on longitudinally confirmed cognitively normal (CN) participants (n= 476). Seven hundred and seventy-nine participants enriched for AD risk were classified as psychometric MCI (pMCI) or CN based on standard and robust norms and "single-test" versus "multi-test" criteria. RESULTS: Prevalence of pMCI ranged from 3% to 49% depending on the classification scheme used. Those classified as pMCI using robust norms exhibited greater subjective cognitive complaints, diagnostic stability, and mild clinical symptoms at follow up. CONCLUSIONS: Results suggest that identifying early clinically relevant cognitive decline in late middle-age is feasible using robust norms and multi test criteria. PMID- 27193364 TI - Facial Emotion Processing in Aviremic HIV-infected Adults. AB - The emotional processing in human immunodeficiency virus-seropositive individuals (HIV+) has been scarcely studied. We included HIV+ individuals (n = 107) on antiretroviral therapy (>=2 years) who completed 6 facial processing tasks and neurocognitive testing. We compared HIV+ and healthy adult (HA) participants (n = 40) in overall performance of each facial processing task. Multiple logistic regressions were conducted to explore predictors of poorer accuracy in those measures in which HIV+ individuals performed poorer than HA participants. We separately explored the impact of neurocognitive status, antiretroviral regimen, and hepatitis C virus (HCV) coinfection on the tasks performance. We found similar performance in overall facial emotion discrimination, recognition, and recall between HIV+ and HA participants. The HIV+ group had poorer recognition of particular negative emotions. Lower WAIS-III Vocabulary scores and active HCV predicted poorer accuracy in recognition of particular emotions. Our results suggest that permanent damage of emotion-related brain systems might persist despite long-term effective antiretroviral therapy. PMID- 27193365 TI - Apolipoprotein E E4, Cognitive Function, and Pain Experience in Down Syndrome: A Pilot Study. AB - OBJECTIVE: The presence of apolipoprotein E (ApoE) E4 allele might be related to higher pain experience due to increased risk for potentially painful physical conditions and cognitive impairment (less efficient coping with pain). This hypothesis is clinically relevant to examine in adults with Down syndrome (DS) because they are at risk for painful physical conditions, their presence of ApoE epsilon4 is related to cognitive impairment, and their pain experience is unclear. The present pilot study addressed the associations between ApoE genotype, cognition, and pain in DS. METHOD: DNA analysis of saliva, neuropsychological tests (assessing memory and executive functioning), and self reporting pain scales (in rest and after movement) were used with a cross sectional design in 146 adults with DS (mean age 39.1 years, mild to moderate intellectual disabilities, 46% men, 30% ApoE E4 carrier). RESULTS: The difference between ApoE E4 carriers and noncarriers was not statistically significant for cognitive function, pain experience, and prevalence of potentially painful conditions. Among E4 carriers, the presence of potentially painful conditions was associated with worse executive functioning (p = .022, r = .39). CONCLUSIONS: The clinical implication of the results is that ApoE E4 in DS may play a role in pain, although the theoretical explanation via associations with pain experience and cognition remains unclear. Further research should include a large sample of adults with DS selected on diagnosed painful conditions to obtain more insight into the possible role of ApoE genotype (and its association with cognition) in the pain experience of this target group. PMID- 27193367 TI - Further Validation of the Conner's Adult Attention Deficit/Hyperactivity Rating Scale Infrequency Index (CII) for Detection of Non-Credible Report of Attention Deficit/Hyperactivity Disorder Symptoms. AB - OBJECTIVE: Attention deficit/hyperactivity disorder (ADHD) can be easily presented in a non-credible manner, through non-credible report of ADHD symptoms and/or by non-credible performance on neuropsychological tests. While most studies have focused on detection of non-credible performance using performance validity tests, there are few studies examining the ability to detect non credible report of ADHD symptoms. We provide further validation data for a recently developed measure of non-credible ADHD symptom report, the Conner's Adult ADHD Rating Scales (CAARS) Infrequency Index (CII). METHOD: Using archival data from 86 adults referred for concerns about ADHD, we examined the accuracy of the CII in detecting extreme scores on the CAARS and invalid reporting on validity indices of the Minnesota Multiphasic Personality Inventory-2 Restructured Format (MMPI-2-RF). We also examined the accuracy of the CII in detecting non-credible performance on standalone and embedded performance validity tests. RESULTS: The CII was 52% sensitive to extreme scores on CAARS DSM symptom subscales (with 97% specificity) and 20%-36% sensitive to invalid responding on MMPI-2-RF validity scales (with near 90% specificity), providing further evidence for the interpretation of the CII as an indicator of non credible ADHD symptom report. However, the CII detected only 18% of individuals who failed a standalone performance validity test (Word Memory Test), with 87.8% specificity, and was not accurate in detecting non-credible performance using embedded digit span cutoffs. CONCLUSIONS: Future studies should continue to examine how best to assess for non-credible symptom report in ADHD referrals. PMID- 27193366 TI - Examining the Association between Patient-Reported Symptoms of Attention and Memory Dysfunction with Objective Cognitive Performance: A Latent Regression Rasch Model Approach. AB - OBJECTIVE: Patient-reported cognition generally exhibits poor concordance with objectively assessed cognitive performance. In this article, we introduce latent regression Rasch modeling and provide a step-by-step tutorial for applying Rasch methods as an alternative to traditional correlation to better clarify the relationship of self-report and objective cognitive performance. An example analysis using these methods is also included. METHOD: Introduction to latent regression Rasch modeling is provided together with a tutorial on implementing it using the JAGS programming language for the Bayesian posterior parameter estimates. In an example analysis, data from a longitudinal neurocognitive outcomes study of 132 breast cancer patients and 45 non-cancer matched controls that included self-report and objective performance measures pre- and post treatment were analyzed using both conventional and latent regression Rasch model approaches. RESULTS: Consistent with previous research, conventional analysis and correlations between neurocognitive decline and self-reported problems were generally near zero. In contrast, application of latent regression Rasch modeling found statistically reliable associations between objective attention and processing speed measures with self-reported Attention and Memory scores. CONCLUSIONS: Latent regression Rasch modeling, together with correlation of specific self-reported cognitive domains with neurocognitive measures, helps to clarify the relationship of self-report with objective performance. While the majority of patients attribute their cognitive difficulties to memory decline, the Rash modeling suggests the importance of processing speed and initial learning. To encourage the use of this method, a step-by-step guide and programming language for implementation is provided. Implications of this method in cognitive outcomes research are discussed. PMID- 27193370 TI - Evaluating Decision-Making: Validation and Regression-Based Normative Data of the Judgment Assessment Tool. AB - OBJECTIVE: This study presents the results of the development and validation of the Judgment Assessment Tool (JAT). The JAT measures two core aspects of judgment, namely generation of solutions (G) and assessment of options (A), the two first stages of decision-making process. METHOD: During the test development phase (study 1), a preliminary version of the JAT was evaluated by 14 experts and tested on 30 healthy controls (HC). One hundred and twenty HC (20-84 years old) and 24 participants with mild Alzheimer's disease (AD) were subsequently tested on the final version of the JAT (study 2). HC participants aged 60 and over and AD participants underwent a neuropsychological evaluation. RESULTS: The internal consistency of the final version of the JAT assessed by Cronbach's a was 0.71 for the HC group and 0.85 for the AD group. Performance on the JAT was normally distributed both in the HC and AD groups. The test correlated with abstract reasoning, verbal fluency, and working memory. Results revealed adequate test retest reliability and excellent interrater reliability (k coefficient was 0.92 for the G section and 0.93 for the A section). Demographically adjusted normative data were generated based on a regression analysis and results showed that AD participants performed worse than HC with a large effect size (Cohen's d = 1.79). CONCLUSION: Overall, these results provide evidence of the reliability and strong construct validity of the JAT to evaluate judgment. PMID- 27193369 TI - Attentional Lapses of Adults with Attention Deficit Hyperactivity Disorder in Tasks of Sustained Attention. AB - Adults with attention deficit hyperactivity disorder (ADHD) show attentional dysfunction such as distractibility and mind-wandering, especially in lengthy tasks. However, fundamentals of dysfunction are ambiguous and relationships of neuropsychological test parameters with self-report measures of ADHD symptoms are marginal. We hypothesize that basic deficits in sustaining attention explain more complex attentional dysfunction in persons with ADHD and relate to ADHD symptoms. Attentional function was analyzed by computing ex-Gaussian parameters for 3 time Blocks in a 20 min test of sustained alertness. Changes in performance across these blocks were analyzed by comparing adult persons with ADHD (n = 24) with healthy matched controls (n = 24) and correlated with neuropsychological measures of selective and divided attention as well as self-report measures of ADHD symptoms. We found a significantly steeper increase in the number of slow responses (ex-Gaussian parameter tau) in persons with ADHD with time on task in basic sustained alertness. They also performed significantly worse in tasks of sustained selective and divided attention. However, after controlling for an increase in tau during the alertness task, significant differences between groups disappeared for divided and partly selective attention. Increases in tau in the sustained alertness task correlated significantly with self-report measures of ADHD symptoms. Our results provide evidence that very basic deficits in sustaining attention in adults with ADHD are related to infrequent slow responses (=attentional lapses), with changes over time being relevant for more complex attentional function and experienced ADHD symptoms in everyday life. PMID- 27193368 TI - One-Year Reference Norms of Cognitive Change in Spanish Old Adults: Data from the NEURONORMA Sample. AB - OBJECTIVE: Serial cognitive assessments are useful for many purposes, such as monitoring cognitive decline or evaluating the result of an intervention. In order to determine if an observed change is reliable and meaningful, longitudinal reference data from non-clinical samples are needed. Since neuropsychological outcomes are affected by language and cultural background, cognitive tests should be adapted, and country-based norms collected. The lack of cross-sectional normative data for Spanish population has been partially remediated, but there is still a need of reliable change norms. This paper aims to give an initial response to this need by providing several reliable change indices (RCI) for 1 year follow-up in a Spanish sample. METHOD: A longitudinal observational study was designed. A total of 122 healthy subjects over age 50 were evaluated twice (M = 369.5, SD= 10.7 days) with the NEURONORMA battery. Scores changes were analyzed, and simple discrepancy scores, standard deviation indices, RCI, and standardized regression-based scores were calculated. RESULTS: Significant improvements were observed in variables related to memory, both verbal and visual, visuospatial function, and the completion time of complex problems. Reference tables for several RCI are provided for their use in clinical settings. CONCLUSIONS: Our results confirm the existence of heterogeneous practice effects after 1 year, and support the recommendation of using reliable change norms to avoid misdiagnosis in repeated assessments. This study provides with initial, preliminary norms of cognitive change for its use in Spanish elders. Further studies on larger samples and different inter-visit intervals are still needed. PMID- 27193371 TI - Heterologous expression of the Hsp24 from Trichoderma asperellum improves antifungal ability of Populus transformant Pdpap-Hsp24 s to Cytospora chrysosperma and Alternaria alternate. AB - The tolerance of plants to biotic and abiotic stresses could be improved by transforming with fungal resistance-related genes. In this study, the cDNA sequence (GenBank Acc. No. KP337939) of the resistance-related gene Hsp24 encoding the 24 kD heat shock protein was obtained from the biocontrol fungus Trichoderma asperellum ACCC30536. The promoter region of Hsp24 contained many cis regulators related to stresses response, such as "GCN4" and "GCR1" etc. Hsp24 transcription in T. asperellum was up-regulated under six different environmental stresses, compared with the control. Furthermore, following heterologous transformation into Populus davidiana * P. alba var. Pyramidalis (Pdpap), Hsp24 was successfully transcribed in transformant Pdpap-Hsp24s. Pathogen-related genes (PRs) in four Pdpap-Hsp24s were up-regulated compared with those in the control Pdpap (Pdpap-Con). After co-culture of Pdpap-Hsp24s with the weak parasite Cytospora chrysosperma, the transcription of genes related to hormone signal pathway (JA and SA) were up-regulated in Pdpap-Hsp24s, and ethidium bromide (EtBr) and Nitro-blue tetrazolium (NBT) staining assays indicated that the cell membrane permeability and the active oxygen content of Pdpap-Hsp24s leaves were lower than that of the control Pdpap-Con. And when the Pdpap-Hsp24s were under the Alternaria alternate stress, the activities of superoxide dismutase (SOD) and peroxidase (POD) got higher in Pdpap-Hsp24s than that in Pdpap-Con, and the disease spots in Pdpap-Con leaves were obviously larger than those in Pdpap Hsp24s leaves. In summary, Hsp24 of T. asperellum ACCC30536 is an important defense response gene, and its heterologous expression improved the resistance of transformant Pdpap-Hsp24s to C. chrysosperma and A. alternate. PMID- 27193372 TI - A Case of Survival: Myocardial Infarction and Ventricular Arrhythmia Induced by Severe Hydrogen Sulfide Poisoning. AB - Most cases of acute hydrogen sulfide (H2S) poisoning in China are caused by sewage processing. With the rapid development of urbanization in China, H2S poisoning is showing an increasing trend. Here, we report a case of survival from severe H2S poisoning. A 40-year-old worker was found in the underground sewer lines. He was unresponsive with bilaterally dilated pupils and had poor oxygen saturation. After intubation, he was transferred to the intensive care unit. He developed respiratory failure, acute myocardial infarction, ventricular arrhythmia and left ventricular function impairment, requiring artificial ventilation with highly concentrated oxygen, hyperbaric oxygen treatment and drug therapy. Consequently, he completely recovered from the respiratory and cardiac failure. Cases of survival after severe H2S intoxication have been rarely reported. Such exposures may bring about severe myocardial impairment, which is most likely to benefit from angiotensin-converting enzyme inhibition and beta blocker. PMID- 27193374 TI - Contact allergy in atopic individuals in relation to allergen-specific immunotherapy. AB - Type I sensitizations and atopic dermatitis (AD) often appear in the same patient. Beneficial effects of allergen-specific immunotherapy (ASIT) in patients with both AD and type I allergies have been reported. The predisposing role of AD to the development of type IV sensitization is discussed. Whether ASIT for type I allergy also influences type IV allergies is unknown. To compare the number of contact allergies between patients with and without AD, before and after one year's treatment with ASIT. A controlled, single-blind multicentre study of children/adults with allergic asthma and/or rhinoconjunctivitis, treated or untreated with ASIT, was performed. The history of AD was collected using questionnaires. The number of contact allergies was assessed by patch testing with a baseline series. 205 individuals completed the study; 133 treated with ASIT (exposed) and 72 before starting ASIT (unexposed). For participants with AD, significantly more contact allergies were found in the groups of all children (p = 0.002), all exposed children (p<0.001), and all exposed study persons (p = 0.013). Independent of AD, significantly more contact allergies were noted in the groups of all unexposed adults (p = 0.004) and all unexposed study persons (p = 0.004). The higher number of contact allergies in patients with AD indicates that AD may be a risk factor for type IV sensitization in those with allergic asthma and/or rhinoconjunctivitis. The lower number of contact allergies in patients exposed to ASIT suggests an immunomodulatory effect on type IV sensitization. PMID- 27193373 TI - Regulating the anticancer properties of organometallic dendrimers using pyridylferrocene entities: synthesis, cytotoxicity and DNA binding studies. AB - A new series of eight first- and second-generation heterometallic ferrocenyl derived metal-arene metallodendrimers, containing ruthenium(ii)-p-cymene, ruthenium(ii)-hexamethylbenzene, rhodium(iii)-cyclopentadienyl or iridium(iii) cyclopentadienyl moieties have been prepared. The metallodendrimers were synthesized by first reacting DAB-(NH2)n (where n = 4 or 8, DAB = diaminobutane) with salicylaldehyde, and then the Schiff-base dendritic ligands were reacted in a one-pot reaction with the appropriate [(eta(6)-p-iPrC6H4Me)RuCl2]2, [(eta(6) C6Me6)RuCl2]2, [(eta(5)-C5Me5)IrCl2]2 or [(eta(5)-C5Me5)RhCl2]2 dimers, in the presence of 4-pyridylferrocene. Heterometallic binuclear analogues were prepared as models of the larger metallodendrimers. All complexes have been characterized using analytical and spectroscopic methods. The cytotoxicity of the heterometallic metallodendrimers and their binuclear analogues were evaluated against A2780 cisplatin-sensitive and A2780cisR cisplatin-resistant human ovarian cancer cell lines and against a non-tumorigenic HEK-293 human embryonic kidney cell line. The second generation Ru(ii)-eta(6)-C6Me6 metallodendrimer is the most cytotoxic and selective compound. DNA binding experiments reveal that a possible mode-of-action of these compounds involves non-covalent interactions with DNA. PMID- 27193377 TI - Ursodeoxycholic Acid Ameliorated Diabetic Nephropathy by Attenuating Hyperglycemia-Mediated Oxidative Stress. AB - Oxidative stress has a great role in diabetes and diabetes induced organ damage. Endoplasmic reticulum (ER) stress is involved in the onset of diabetic nephropathy. We hypothesize that ER stress inhibition could protect against kidney injury through anti-oxidative effects. To test whether block ER stress could attenuate oxidative stress and improve diabetic nephropathy in vivo and in vitro, the effect of ursodeoxycholic acid (UDCA), an ER stress inhibitor, on spontaneous diabetic nephropathy db/db mice, ER stress inducer or high glucose triggered podocytes were studied. Mice were assigned to 3 groups (n=6 per group): control group (treated with vehicle), db/db group (treated with vehicle), and UDCA group (db/db mice treated with 40 mg/kg/d UDCA). After 8 weeks treatment, mice were sacrificed. Blood and kidneys were collected for the assessment of albumin/creatinine ratio, blood urea nitrogen (BUN), serum creatinine (SCr), insulin, total cholesterol, triglyceride, low density lipoprotein cholesterol (LDL-C), oxidized LDL-C, high density lipoprotein cholesterol (HDL-C), non esterified fatty acid (NEFA), superoxide dismutase (SOD), catalase (CAT), methane dicarboxylic aldehyde (MDA), the expressions of SOD isoforms and glutathione peroxidase 1, as well as histopathological examination. In addition, generation of reactive oxygen species (ROS) was detected by 2'7'-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescence. The results showed that UDCA alleviated renal ER stress-evoked cell death, oxidative stress, renal dysfunction, ROS production, upregulated the expression of Bcl-2 and suppressed Bax in vivo and in vitro. Hence, inhibition ER stress diminishes oxidative stress and exerts renoprotective effects. PMID- 27193378 TI - Negletein as a neuroprotectant enhances the action of nerve growth factor and induces neurite outgrowth in PC12 cells. AB - Negletein has been shown to have therapeutic potential for inflammation associated diseases, but its effect on neurite outgrowth is still unknown. The present study showed that negletein alone did not trigger PC12 cells to differentiate and extend neurites. When compared with the cells in the untreated control, a significant (P < 0.05) induction and a higher neurite outgrowth activity was observed when the cells were cotreated with negletein (10 uM) and a low dose of nerve growth factor (NGF; 5 ng/mL). The neurite outgrowth process was blocked by the tyrosine kinase receptor (Trk) inhibitor, K252a, suggesting that the neuritogenic effect was NGF-dependent. Negletein (10 uM) together with NGF (5 ng/mL) enhanced the phosphorylation of extracellular signal-regulated kinases (ERKs), protein kinase B (Akt), and cAMP response element-binding protein (CREB). The growth associated protein-43 (GAP-43) and the NGF level were also upregulated by negletein (10 uM) and a low dose of NGF (5 ng/mL). Negletein at nanomolar concentration also was found to be sufficient to mediate the survival of serum deprived PC12 cells up to 72 h. Taken together, negletein might be useful as an efficient bioactive compound to protect neurons from cell death and promote neuritogenesis. (c) 2016 BioFactors, 42(6):591-599, 2016. PMID- 27193379 TI - Photolithographically Patterned TiO2 Films for Electrolyte-Gated Transistors. AB - Metal oxides constitute a class of materials whose properties cover the entire range from insulators to semiconductors to metals. Most metal oxides are abundant and accessible at moderate cost. Metal oxides are widely investigated as channel materials in transistors, including electrolyte-gated transistors, where the charge carrier density can be modulated by orders of magnitude upon application of relatively low electrical bias (2 V). Electrolyte gating offers the opportunity to envisage new applications in flexible and printed electronics as well as to improve our current understanding of fundamental processes in electronic materials, e.g. insulator/metal transitions. In this work, we employ photolithographically patterned TiO2 films as channels for electrolyte-gated transistors. TiO2 stands out for its biocompatibility and wide use in sensing, electrochromics, photovoltaics and photocatalysis. We fabricated TiO2 electrolyte gated transistors using an original unconventional parylene-based patterning technique. By using a combination of electrochemical and charge carrier transport measurements we demonstrated that patterning improves the performance of electrolyte-gated TiO2 transistors with respect to their unpatterned counterparts. Patterned electrolyte-gated (EG) TiO2 transistors show threshold voltages of about 0.9 V, ON/OFF ratios as high as 1 * 10(5), and electron mobility above 1 cm(2)/(V s). PMID- 27193376 TI - Heme pathway evolution in kinetoplastid protists. AB - BACKGROUND: Kinetoplastea is a diverse protist lineage composed of several of the most successful parasites on Earth, organisms whose metabolisms have coevolved with those of the organisms they infect. Parasitic kinetoplastids have emerged from free-living, non-pathogenic ancestors on multiple occasions during the evolutionary history of the group. Interestingly, in both parasitic and free living kinetoplastids, the heme pathway-a core metabolic pathway in a wide range of organisms-is incomplete or entirely absent. Indeed, Kinetoplastea investigated thus far seem to bypass the need for heme biosynthesis by acquiring heme or intermediate metabolites directly from their environment. RESULTS: Here we report the existence of a near-complete heme biosynthetic pathway in Perkinsela spp., kinetoplastids that live as obligate endosymbionts inside amoebozoans belonging to the genus Paramoeba/Neoparamoeba. We also use phylogenetic analysis to infer the evolution of the heme pathway in Kinetoplastea. CONCLUSION: We show that Perkinsela spp. is a deep-branching kinetoplastid lineage, and that lateral gene transfer has played a role in the evolution of heme biosynthesis in Perkinsela spp. and other Kinetoplastea. We also discuss the significance of the presence of seven of eight heme pathway genes in the Perkinsela genome as it relates to its endosymbiotic relationship with Paramoeba. PMID- 27193380 TI - Modification of decellularized vascular scaffold with conditioned medium to enhance cell reseeding. AB - Repopulation of decellularized vascular scaffolds (DVS) is limited because of change in the repertoire and ratios of the remaining extracellular matrix (ECM) proteins, for example, loss of glycoproteins and the retention of type I collagen. Pre-treatment of DVS with defined ECM proteins, which match the repertoire of integrin receptors expressed by the embryonic stem cells (mESCs) to be seeded, can increase the reseeding efficacy. mESCs mainly express high levels of functional receptors for LM and FN. Reseeding efficiency of DVS with mESCs was very low, but was sigficantly increased (2.5 +/- 0.1 fold) by pre-treating the DVS with A549-conditioned media. In addition, pre-treatment with A549-conditioned media led to a more homogeneous distribution of the seeded mESCs throughout the engineered blood vessel as compared to untreated DVS. This paper may promote blood vessel engineering by stressing the importance of matching the cell binding motifs of DVS and the integrin receptor repertoire of seeded cells. PMID- 27193382 TI - Patterns and predictors of undiagnosed and uncontrolled hypertension: observations from a poor-resource setting. AB - Early detection is the cornerstone of hypertension management; still majority remains undetected until complications arise, especially in poor-resource settings. Paucity of information regarding undiagnosed and uncontrolled hypertension in eastern India thus called for a detailed investigation involving a representative sample of adults in Malda, one of the poorest districts in the region. In a cross-sectional study, between October 2013 and July 2014, using multistage random sampling with probability-proportional-to-size, 18 028 consenting adults were interviewed. Diagnosed cases were defined as uncontrolled if they still had hypertensive level of blood pressure (according to JNC-VIII criteria) while those detected during this study were defined as undiagnosed. Descriptive and regression analyses were performed using SAS version 9.3.2. Among 18 028 participants, 4695 (26.04% (95% confidence intervals: 95% CI=25.40-26.68)) had hypertension, of which 3937 (83.86% (82.80-84.91)) were undiagnosed and 548 (72.30 (69.10-75.49)) had uncontrolled hypertension. Relatively older subjects (adjusted Odds ratio (aOR)41-60 years=0.34 (95% CI=0.26-0.43) and aOR>60 years=0.29 (0.21-0.38)), who were divorced/separated/widowed/widower (aOR=0.76 (0.61-0.95)), had higher education (aOR=0.61 (0.43-0.88)), better socio-economic status (SES) (aORMiddle=0.77 (0.60-0.99) and aORUpper=0.64 (0.48-0.85)) and urban residence (aOR=0.44 (0.36-0.55)) were less likely while subjects who belonged to backward castes (aOR=1.37 (1.15-1.64)) were more likely to have undiagnosed hypertension. Odds of having uncontrolled hypertension were higher among participants aged >60 years (aOR=2.25 (1.27-3.99)). Burden of hypertension (diagnosed and undiagnosed) was high in Malda district of West Bengal. Significant predictors of undiagnosed hypertension were young age, backward caste, poor education and lower SES, while older subjects had poor control. Thus, appropriate surveillance targeting these at-risk groups might be effective in controlling hypertension in similar poor-resource settings. PMID- 27193381 TI - Gold Nanoparticle Coated Carbon Nanotube Ring with Enhanced Raman Scattering and Photothermal Conversion Property for Theranostic Applications. AB - We report a new type of carbon nanotube ring (CNTR) coated with gold nanoparticles (CNTR@AuNPs) using CNTR as a template and surface attached redox active polymer as a reducing agent. This nanostructure of CNTR bundle embedded in the gap of closely attached AuNPs can play multiple roles as a Raman probe to detect cancer cells and a photoacoustic (PA) contrast agent for imaging-guided cancer therapy. The CNTR@AuNP exhibits substantially higher Raman and optical signals than CNTR coated with a complete Au shell (CNTR@AuNS) and straight CNT@AuNP. The extinction intensity of CNTR@AuNP is about 120-fold higher than that of CNTR at 808 nm, and the surface enhanced Raman scattering (SERS) signal of CNTR@AuNP is about 110 times stronger than that of CNTR, presumably due to the combined effects of enhanced coupling between the embedded CNTR and the plasmon mode of the closely attached AuNPs, and the strong electromagnetic field in the cavity of the AuNP shell originated from the intercoupling of AuNPs. The greatly enhanced PA signal and photothermal conversion property of CNTR@AuNP were successfully employed for imaging and imaging-guided cancer therapy in two tumor xenograft models. Experimental observations were further supported by numerical simulations and perturbation theory analysis. PMID- 27193383 TI - Thermosensitive magnetic liposomes with doxorubicin cell-penetrating peptides conjugate for enhanced and targeted cancer therapy. AB - To specifically deliver cytotoxic drug to tumor cells and enhance cellular uptake is the key for effective cancer therapy. In this paper, we described a novel drug targeting system, which is designed to combine features of biological (cell penetrating peptides, CPPs) and physical (magnetic) drug targeting for use in the magnetic hyperthermia-triggered release. A doxorubicin-CPPs conjugate (DOX-CPPs) was loaded into thermosensitive magnetic liposomes (TSMLs) (DOX-CPPs/TSMLs), and in vitro DOX-CPPs thermosensitive release activity, anti-proliferation effect, in vivo targeted delivery as well as in vivo antitumor activity were determined. The results demonstrated that the DOX-CPPs/TSMLs showed good physicochemical properties, effective anti-proliferation effect in MCF-7 cells in vitro. Additionally, in vivo study, DOX-CPPs/TSMLs under AC magnetic field displayed superior in vivo targeted delivery efficacy, antitumor efficacy in an MCF-7 xenograft murine model. In conclusion, the application of DOX-CPPs/TSMLs under AC magnetic field may provide a strategy for the selective and efficient delivery of drug. PMID- 27193384 TI - Black perithecial pigmentation in Fusarium species is due to the accumulation of 5-deoxybostrycoidin-based melanin. AB - Biosynthesis of the black perithecial pigment in the filamentous fungus Fusarium graminearum is dependent on the polyketide synthase PGL1 (oPKS3). A seven membered PGL1 gene cluster was identified by over-expression of the cluster specific transcription factor pglR. Targeted gene replacement showed that PGL1, pglJ, pglM and pglV were essential for the production of the perithecial pigment. Over-expression of PGL1 resulted in the production of 6-O-demethyl-5 deoxybostrycoidin (1), 5-deoxybostrycoidin (2), and three novel compounds 5 deoxybostrycoidin anthrone (3), 6-O-demethyl-5-deoxybostrycoidin anthrone (4) and purpurfusarin (5). The novel dimeric bostrycoidin purpurfusarin (5) was found to inhibit the growth of Candida albicans with an IC50 of 8.0 +/- 1.9 MUM. The results show that Fusarium species with black perithecia have a previously undescribed form of 5-deoxybostrycoidin based melanin in their fruiting bodies. PMID- 27193385 TI - Serum replacement with albumin-associated lipids prevents excess aggregation and enhances growth of induced pluripotent stem cells in suspension culture. AB - Suspension culture systems are currently under investigation for the mass production of pluripotent stem (PS) cells for tissue engineering; however, the control of cell aggregation in suspension culture remains challenging. Existing methods to control aggregation such as microwell culture are difficult to scale up. To address this issue, in this study a novel method that incorporates the addition of KnockOut Serum Replacement (KSR) to the PS cell culture medium was described. The method regulated cellular aggregation and significantly improved cell growth (a 2- to 10-fold increase) without any influence on pluripotency. In addition, albumin-associated lipids as the major working ingredient of KSR responsible for this inhibition of aggregation were identified. This is one of the simplest methods described to date to control aggregation and requires only chemically synthesizable reagents. Thus, this method has the potential to simplify the mass production process of PS cells and thus lower their cost. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1009-1016, 2016. PMID- 27193387 TI - In silico Structural characterization of podocin and assessment of nephrotic syndrome-associated podocin mutants. AB - Nephrotic syndrome (NS) is manifested by hyperproteinuria, hypoalbuminemia, and edema. NPHS2 that encodes podocin was found to have most mutations among the genes that are involved in the pathophysiology of NS. Podocin, an integral membrane protein belonging to stomatin family, is expressed exclusively in podocytes and is localized to slit-diaphragm (SD). Mutations in podocin are known to be associated with steroid-resistant NS and rapid progression to end-stage renal disease, thus signifying its role in maintaining SD integrity and podocyte function. The structural insights of podocin are not known, and the precise mechanism by which podocin contributes to the architecture of SD is yet to be elucidated. In this study, we deduced a model for human podocin, discussed the details of transmembrane localization and intrinsically unstructured regions, and provide an understanding of how podocin interacts with other SD components. Intraprotein interactions were assessed in wild-type podocin and in some of its mutants that are associated with idiopathic NS. Mutations in podocin alter the innate intraprotein interactions affecting the native structure of podocin and its ability to form critical complex with subpodocyte proteins. (c) 2016 IUBMB Life, 68(7):578-588, 2016. PMID- 27193389 TI - Amplification, Decoherence, and the Acquisition of Information by Spin Environments. AB - Quantum Darwinism recognizes the role of the environment as a communication channel: Decoherence can selectively amplify information about the pointer states of a system of interest (preventing access to complementary information about their superpositions) and can make records of this information accessible to many observers. This redundancy explains the emergence of objective, classical reality in our quantum Universe. Here, we demonstrate that the amplification of information in realistic spin environments can be quantified by the quantum Chernoff information, which characterizes the distinguishability of partial records in individual environment subsystems. We show that, except for a set of initial states of measure zero, the environment always acquires redundant information. Moreover, the Chernoff information captures the rich behavior of amplification in both finite and infinite spin environments, from quadratic growth of the redundancy to oscillatory behavior. These results will considerably simplify experimental testing of quantum Darwinism, e.g., using nitrogen vacancies in diamond. PMID- 27193388 TI - TNFalpha promotes CAR-dependent migration of leukocytes across epithelial monolayers. AB - Trans-epithelial migration (TEpM) of leukocytes during inflammation requires engagement with receptors expressed on the basolateral surface of the epithelium. One such receptor is Coxsackie and Adenovirus Receptor (CAR) that binds to Junctional Adhesion Molecule-like (JAM-L) expressed on leukocytes. Here we provide the first evidence that efficient TEpM of monocyte-derived THP-1 cells requires and is controlled by phosphorylation of CAR. We show that TNFalpha acts in a paracrine manner on epithelial cells via a TNFR1-PI3K-PKCdelta pathway leading to CAR phosphorylation and subsequent transmigration across cell junctions. Moreover, we show that CAR is hyper-phosphorylated in vivo in acute and chronic lung inflammation models and this response is required to facilitate immune cell recruitment. This represents a novel mechanism of feedback between leukocytes and epithelial cells during TEpM and may be important in controlling responses to pro-inflammatory cytokines in pathological settings. PMID- 27193386 TI - Neurocognitive, Neuroprotective, and Cardiometabolic Effects of Raloxifene: Potential for Improving Therapeutic Outcomes in Schizophrenia. AB - Raloxifene is a selective estrogen receptor modulator that has been approved for treating osteoporosis and breast cancer in high-risk postmenopausal women. However, recent evidence suggests that raloxifene adjunct therapy improves cognition and reduces symptom severity in men and women with schizophrenia. In animal models, raloxifene increases forebrain neurogenesis and enhances working memory and synaptic plasticity. It may consequently repair the neuronal and synaptic connectivity that is disrupted in schizophrenia. It also reduces oxidative stress and neuroinflammation, which are potent etiological factors in the neuropathology of schizophrenia. Furthermore, in postmenopausal women, raloxifene reduces the risks for atherosclerosis, diabetes mellitus, and weight gain, which are serious adverse effects associated with long-term antipsychotic treatment in schizophrenia; therefore, it may improve the safety and efficacy of antipsychotic drugs. In this review, recent insights into the neurocognitive, neuroprotective, and cardiometabolic effects of raloxifene in relation to therapeutic outcomes in schizophrenia are discussed. PMID- 27193391 TI - Facile Fabrication of Binary Nanoscale Interface for No-Loss Microdroplet Transportation. AB - Binary nanoscale interfacial materials are fundamental issues in many applications for smart surfaces. A binary nanoscale interface with binary surface morphology and binary wetting behaviors has been prepared by a facile wet chemical method. The prepared surface presents superhydrophobicity and high adhesion with the droplet at the same time. The composition, surface morphology, and wetting behaviors of the prepared surface have been systematic studied. The special wetting behaviors can be contributed to the binary nanoscale effect. The stability of the prepared surface was also investigated. As a primary application, a facile device based on the prepared binary nanoscale interface with superhydrophobicity and high adhesion was constructed for microdroplet transportation. PMID- 27193390 TI - Varying proliferative and clonogenic potential in NRAS-mutated congenital melanocytic nevi according to size. AB - Congenital melanocytic nevi (CMN) are benign proliferations that may be associated with various consequences depending on their size. They are characterized by a specific molecular signature, namely a postzygotic somatic NRAS or BRAF mutation. We have recently reported that large CMN (lCMN), which are classically associated with an increased melanoma risk, harbour cell subpopulations with specific clonogenic and tumorigenic potential. We wished to ascertain whether cells displaying similar properties persisted postnatally in medium CMN (mCMN). Eighteen medium M1, nine large and one giant NRAS-mutated CMN were prospectively included in the study. Subpopulations of mCMN cells expressed stem cell/progenitor lineage markers such as Sox10, nestin and Oct4, as was the case in lCMN. Nevertheless, conversely to lCMN, mCMN cells with clonogenic properties were rarer. In vitro, approximatively one in 1500 cells isolated from fresh mCMN formed colonies that could be passaged. In vivo, mCMN seemed to harbour cells with less proliferative potential than the larger lesions as lCMN biopsies displayed a threefold expansion compared to mCMN when xenografted in Rag2(-/-) mice. Thus, our data revealed variations in clonogenicity and tumorigenic properties in NRAS-mutated CMN according to size. PMID- 27193392 TI - DgcA, a diguanylate cyclase from Xanthomonas oryzae pv. oryzae regulates bacterial pathogenicity on rice. AB - Xanthomonas oryzae pv. oryzae (Xoo) is the causal agent of rice blight disease as well as a serious phytopathogen worldwide. It is also one of the model organisms for studying bacteria-plant interactions. Current progress in bacterial signal transduction pathways has identified cyclic di-GMP as a major second messenger molecule in controlling Xanthomonas pathogenicity. However, it still remains largely unclear how c-di-GMP regulates the secretion of bacterial virulence factors in Xoo. In this study, we focused on the important roles played by DgcA (XOO3988), one of our previously identified diguanylate cyclases in Xoo, through further investigating the phenotypes of several dgcA-related mutants, namely, the dgcA-knockout mutant DeltadgcA, the dgcA overexpression strain OdgcA, the dgcA complemented strain CdgcA and the wild-type strain. The results showed that dgcA negatively affected virulence, EPS production, bacterial autoaggregation and motility, but positively triggered biofilm formation via modulating the intracellular c-di-GMP levels. RNA-seq data further identified 349 differentially expressed genes controlled by DgcA, providing a foundation for a more solid understanding of the signal transduction pathways in Xoo. Collectively, the present study highlights DgcA as a major regulator of Xoo virulence, and can serve as a potential target for preventing rice blight diseases. PMID- 27193393 TI - Ligand Specific Efficiency (LSE) Index for PET Tracer Optimization. AB - Ligand efficiency indices are widely used to guide chemical optimization in drug discovery, due to their predictive value in the early steps of optimization. At later stages, however, as more complex properties become critical for success, indices relying on calculated, rather than experimental, parameters become less informative. This problem is particularly acute when developing positron emission tomography (PET) imaging agents, for which nonspecific binding (NSB) to membranes and non-target proteins is a frequent cause of failure. NSB cannot be predicted using in silico parameters. To address this gap, we explored the use of the experimentally determined chromatographic hydrophobicity index on immobilized artificial membranes, CHI(IAM), to guide the optimization of NSB. The ligand specific efficiency (LSE) index was defined as the ratio between affinity (pIC50 or pKd ) and the logarithmic value of CHI(IAM). It allows for quantification of binding affinity to the target of interest, relative to NSB. Its use was illustrated by the optimization of PET tracer candidates for the prostacyclin receptor. PMID- 27193394 TI - Vascular control of the Drosophila haematopoietic microenvironment by Slit/Robo signalling. AB - Self-renewal and differentiation of mammalian haematopoietic stem cells (HSCs) are controlled by a specialized microenvironment called 'the niche'. In the bone marrow, HSCs receive signals from both the endosteal and vascular niches. The posterior signalling centre (PSC) of the larval Drosophila haematopoietic organ, the lymph gland, regulates blood cell differentiation under normal conditions and also plays a key role in controlling haematopoiesis under immune challenge. Here we report that the Drosophila vascular system also contributes to the lymph gland homoeostasis. Vascular cells produce Slit that activates Robo receptors in the PSC. Robo activation controls proliferation and clustering of PSC cells by regulating Myc, and small GTPase and DE-cadherin activity, respectively. These findings reveal that signals from the vascular system contribute to regulating the rate of blood cell differentiation via the regulation of PSC morphology. PMID- 27193396 TI - An observational study of sequential protein-sparing, very low-calorie ketogenic diet (Oloproteic diet) and hypocaloric Mediterranean-like diet for the treatment of obesity. AB - The impact of a rehabilitative multi-step dietary program consisting in different diets has been scantily investigated. In an open-label study, 73 obese patients underwent a two-phase weight loss (WL) program: a 3-week protein-sparing, very low-calorie, ketogenic diet (<500 kcal/day; Oloproteic((r)) Diet) and a 6-week hypocaloric (25-30 kcal/kg of ideal body weight/day), low glycemic index, Mediterranean-like diet (hypo-MD). Both phases improved visceral adiposity, liver enzymes, GH levels, blood pressure and glucose and lipid metabolism. However, the hypo-MD was responsible for a re-increase in blood lipids and glucose tolerance parameters. Changes in visceral adiposity and glucose control-related variables were more consistent in patients with metabolic syndrome. However, in these patients the hypo-MD did not result in a consistent re-increase in glucose control-related variables. A dietary program consisting in a ketogenic regimen followed by a balanced MD appeared to be feasible and efficacious in reducing cardiovascular risk, particularly in patients with metabolic syndrome. PMID- 27193395 TI - A knowledge synthesis of culturally- and spiritually-sensitive end-of-life care: findings from a scoping review. AB - BACKGROUND: Multiple factors influence the end-of-life (EoL) care and experience of poor quality services by culturally- and spiritually-diverse groups. Access to EoL services e.g. health and social supports at home or in hospices is difficult for ethnic minorities compared to white European groups. A tool is required to empower patients and families to access culturally-safe care. This review was undertaken by the Canadian Virtual Hospice as a foundation for this tool. METHODS: To explore attitudes, behaviours and patterns to utilization of EoL care by culturally and spiritually diverse groups and identify gaps in EoL care practice and delivery methods, a scoping review and thematic analysis of article content was conducted. Fourteen electronic databases and websites were searched between June-August 2014 to identify English-language peer-reviewed publications and grey literature (including reports and other online resources) published between 2004-2014. RESULTS: The search identified barriers and enablers at the systems, community and personal/family levels. Primary barriers include: cultural differences between healthcare providers; persons approaching EoL and family members; under-utilization of culturally-sensitive models designed to improve EoL care; language barriers; lack of awareness of cultural and religious diversity issues; exclusion of families in the decision-making process; personal racial and religious discrimination; and lack of culturally-tailored EoL information to facilitate decision-making. CONCLUSIONS: This review highlights that most research has focused on decision-making. There were fewer studies exploring different cultural and spiritual experiences at the EoL and interventions to improve EoL care. Interventions evaluated were largely educational in nature rather than service oriented. PMID- 27193398 TI - Performance of the Striped Mealybug Ferrisia virgata Cockerell (Hemiptera: Pseudococcidae) under Variable Conditions of Temperature and Mating. AB - Mealybugs have strong associations with their host plants due to their limitations for dispersal. Thus, environmental conditions and host quality may impact the biological traits of mealybugs. To the best of our knowledge, we are the first to report on the biology of a Brazilian population of the striped mealybug Ferrisia virgata Cockerell (Hemiptera: Pseudococcidae), which has recently been reported to infest cotton in Brazil. We evaluated the development and reproductive performance of F. virgata reared under different temperatures (25, 27, and 28 degrees C) and mating status. The type of reproduction was also studied with insects reared on a factitious host and on cotton plants. Shorter development was obtained at 28 degrees C as follows: nymphs generating males and females exhibited three and four instars with a mean duration of 19.1 and 20.5 days, respectively. The nymphal viability ranged from 77 to 96%, and was highest at 25 degrees C. Females reared at 28 degrees C initiated reproduction earlier (16.4 days), but the reproductive period was similar in all temperatures (~16.2 days). Females produced more nymphs at 27 and 28 degrees C (440 and 292 neonates) than at 25 degrees C (277 neonates), although they lived longer at 25 degrees C (63 days). Ferrisia virgata females exhibited only sexual reproduction. Thus, only mated females produced offspring, whereas unmated females died without reproducing. Therefore, the studied population of F. virgata exhibited only sexual reproduction with high survival and offspring production when fed cotton. Furthermore, pumpkin is a feasible host for mass rearing this mealybug species in the laboratory, an opening avenue for future studies. PMID- 27193397 TI - Peptide-based systems analysis of inflammation induced myeloid-derived suppressor cells reveals diverse signaling pathways. AB - A better understanding of molecular signaling between myeloid-derived suppressor cells (MDSC), tumor cells, T-cells, and inflammatory mediators is expected to contribute to more effective cancer immunotherapies. We focus on plasma membrane associated proteins, which are critical in signaling and intercellular communication, and investigate changes in their abundance in MDSC of tumor bearing mice subject to heightened versus basal inflammatory conditions. Using spectral counting, we observed statistically significant differential abundances for 35 proteins associated with the plasma membrane, most notably the pro inflammatory proteins S100A8 and S100A9 which induce MDSC and promote their migration. We also tested whether the peptides associated with canonical pathways showed a statistically significant increase or decrease subject to heightened versus basal inflammatory conditions. Collectively, these studies used bottom-up proteomic analysis to identify plasma membrane associated pro-inflammatory molecules and pathways that drive MDSC accumulation, migration, and suppressive potency. PMID- 27193399 TI - Phenological Patterns and Preferences for Aromatic Compounds by Male Euglossine Bees (Hymenoptera, Apidae) in Two Coastal Ecosystems of the Brazilian Atlantic Forest. AB - In order to investigate phenological patterns and seasonal and geographic variations in the preference for fragrances of Euglossini males, monthly sampling was carried out from August 2007 to July 2009 in two coastal areas of Atlantic Forest in Ubatuba, northern coast of the state of Sao Paulo. Fourteen aromatic baits were used, 3 of them in the first year (August 2007 to July 2008) and the other 11 in the second year (August 2008 to July 2009). A total of 1,475 individuals from 22 species were collected. The highest frequency of the individuals of the majority of the sampled species occurred in the hot/super humid season. However, Eulaema cingulata (Fabricius) showed peaks of abundance in the cold/less-humid season on Anchieta Island. Seasonal variation in fragrance choice by males was not registered. Males of El. cingulata showed preference for beta-ionone on Anchieta Island and for benzyl acetate in the Picinguaba region, characterizing the single example of geographic variation in preference for scent baits we recorded. PMID- 27193400 TI - Larval Distribution and Behavior of Chrysomya rufifacies (Macquart) (Diptera: Calliphoridae) Relative to Other Species on Florida Black Bear (Carnivora: Ursidae) Decomposing Carcasses. AB - Larval interactions of dipteran species, blow flies in particular, were observed and documented daily over time and location on five black bear carcasses in Gainesville, FL, USA, from June 2002 - September 2004. Cochliomyia macellaria (Fabricius) or Chrysomya megacephala (Fabricius) larvae were collected first, after which Chrysomya rufifacies (Macquart) oviposited on the carcasses in multiple locations (i.e., neck, anus, and exposed flesh) not inhabited already by the other blow fly larvae. Within the first week of decomposition, C. rufifacies larvae grew to >=12 mm, filling the carcasses with thousands of larvae and replacing the other calliphorid larvae either through successful food source competition or by predation. As a result, C. macellaria and C. megacephala were not collected past their third instar feeding stage. The blow fly species, C. megacephala, C. macellaria, Lucilia caeruleiviridis (Macquart), Phormia regina (Meigen), Lucilia sericata (Meigen), and C. rufifacies, completed two developmental cycles in the 88.5-kg carcass. This phenomenon might serve to complicate or prevent the calculation of an accurate postmortem interval. PMID- 27193401 TI - Skipper Richness (Hesperiidae) Along Elevational Gradients in Brazilian Atlantic Forest. AB - Hesperiidae are claimed to be a group of elusive butterflies that need major effort for sampling, thus being frequently omitted from tropical butterfly surveys. As no studies have associated species richness patterns of butterflies with environmental gradients of high altitudes in Brazil, we surveyed Hesperiidae ensembles in Serra do Mar along elevational transects (900-1,800 m above sea level) on three mountains. Transects were sampled 11-12 times on each mountain to evaluate how local species richness is influenced by mountain region, vegetation type, and elevational zones. Patterns were also analyzed for the subfamilies, and after disregarding species that exhibit hilltopping behavior. Species richness was evaluated by the observed richness, Jacknife2 estimator and Chao 1 estimator standardized by sample coverage. Overall, 155 species were collected, but extrapolation algorithms suggest a regional richness of about 220 species. Species richness was far higher in forest than in early successional vegetation or grassland. Richness decreased with elevation, and was higher on Anhangava mountain compared with the two others. Patterns were similar between observed and extrapolated Jacknife2 richness, but vegetation type and mountain richness became altered using sample coverage standardization. Hilltopping species were more easily detected than species that do not show this behavior; however, their inclusion did neither affect estimated richness nor modify the shape of the species accumulation curve. This is the first contribution to systematically study highland butterflies in southern Brazil where all records above 1,200 m are altitudinal extensions of the known geographical ranges of skipper species in the region. PMID- 27193403 TI - Effect of Lunar Phases, Tides, and Wind Speed on the Abundance of Diptera Calliphoridae in a Mangrove Swamp. AB - Abiotic factors, such as lunar phases and tides, have a significant effect on insect development. Reproduction and immature development are usually interlinked to these abiotic factors. The tide is at its highest levels at full moon or new moon, hindering the feeding of the immature or causing their drowning. The oviposition by adult females is also compromised on these days because much of the available food is submerged. Another important abiotic factor is the wind, which displaces odoriferous particles in the air. Wind speed and direction are important elements to indicate potential sources of food for insects. I report on the effects of lunar phases, tides, and wind speed on the Calliphoridae fauna in mangrove swamps. The different species collected were identified, and the predominant species in the area were quantified. A total of 1,710 flies were collected over a 1-year period. Six Calliphoridae flies, Chloroprocta idioidea (Robineau-Desvoidy), Chrysomya megacephala (Fabricius), Chrysomya albiceps (Wiedemann), Chrysomya putoria (Wiedemann), Cochliomyia macellaria (Fabricius), and Lucilia eximia (Wiedemann) were collected. Data indicated that lunar phases have a significant effect on the abundance of C. albiceps (r = 0.39, p < 0.01), and that the variation of the tides also affected the abundance of C. putoria (r = 0.40, p < 0.00), C. macellaria (r = 0.41, p < 0.00), and C. idioidea (r = 0.31, p < 0.04). The wind speed, however, did not affect these species. PMID- 27193402 TI - Evidence for the Deflective Function of Eyespots in Wild Junonia evarete Cramer (Lepidoptera, Nymphalidae). AB - Junonia evarete Cramer is a fast-flying butterfly that perches on the ground with wings opened exhibiting four eyespots close to wing borders. These eyespots presumably function either to intimidate predators, like insectivorous birds, or to deflect bird attacks to less vital parts of the body. We assessed the form, frequency, and location of beak marks on the wings of wild butterflies in central Brazil during two not consecutive years. We found that almost 50% of males and 80% of females bore signals of predator attacks (wing tears), most of them consisting of partially or totally V-shaped forms apparently produced by birds. Males were significantly less attacked and showed a lower proportion of attacks on eyespots than females, suggesting they are better to escape bird attacks. In contrast, females were heavily attacked on eyespots. Eyespot tears in females were higher (and significant different) than expected by chance, indicating that birds do attempt to reach the eyespots when striking on these butterflies. Other comparisons involving the proportion of tears directed or not directed to eyespots in males and females are presented and discussed. PMID- 27193404 TI - Floral Preference of Melipona eburnea Friese (Hymenoptera: Apidae) in a Colombian Andean Region. AB - Melipona eburnea Friese is a stingless bee kept in some regions of Colombia, where it is reported to be vulnerable to extinction due to habitat disturbance. To contribute to raising conservation strategies, the aim of this study was to identify the floral preferences of this species using melissopalynological analysis. A total of 31 pollen pot samples and 37 honey samples were taken from March 2009 through March 2010 from four colonies in Fusagasuga, Colombia. We found 92 pollen types: 17 from pollen pot samples, 39 from honey samples (indicating the sources of nectar), and 36 in both types of samples. The most frequent pollen types in the pollen pot samples were Myrcia type (100%), Eucalyptus globulus (96.9%), and Fraxinus uhdei (96.9%). The most frequent pollen types in honey samples were E. globulus (97.4%) and Myrcia type (94.9%). The pollen types corresponded mainly to native plants (68%), trees (44.5%), plants whose sexual system is hermaphroditic (56.5%), and plants with inflorescences (76.2%). The most frequent shapes of the flowers were brush-like (type Myrtaceae) and dish-like (type Asteraceae), and the preferred flower colors were white or cream (52.2%). In general, we found that M. eburnea showed a strong preference for trees of the family Myrtaceae to obtain nectar and pollen, including native and introduced species. Some other families are contributing significantly, such as Melastomataceae for pollen collection and Asteraceae for nectar. These results highlight the key plant species for the diet of M. eburnea. PMID- 27193405 TI - Erratum to: Floral Preference of Melipona eburnea Friese (Hymenoptera: Apidae) in a Colombian Andean Region. PMID- 27193406 TI - New Species and New Records of Dexosarcophaga Townsend (Diptera: Sarcophagidae) from Brazil with a Key to Species of the Subgenus Bezzisca. AB - Dexosarcophaga tupinamba n. sp. is described based on male specimens from the Brazilian states of Para and Maranhao; Dexosarcophaga bermudezi Silva & Mello Patiu is newly recorded from Para and South America; and Dexosarcophaga avispaensis Mello is newly recorded from Para (new to Brazil). The Brazilian species Dexosarcophaga limitata (Lopes) and Dexosarcophaga pusilla (Lopes) are both recorded from Para, which are new records from the Brazilian Amazon, Dexosarcophaga aurifacies (Lopes) is newly recorded from the state of Alagoas and Dexosarcophaga carvalhoi (Lopes) is newly recorded from the states of Mato Grosso, Maranhao, and Para. A key to the identification of males of the subgenus Bezzisca is provided. PMID- 27193407 TI - Description of a New Species of the Andean Butterfly Genus Forsterinaria Gray (Lepidoptera: Nymphalidae) with Considerations on an Apparently New Structure in Male Genitalia. AB - The butterfly genus Forsterinaria Gray is the only strictly montane representative of the diverse Neotropical subtribe Euptychiina (Nymphalidae, Satyrinae), with 24 described species. Recent research in some of the most isolated and highly diverse Andean regions, such as central Peru, show that its total species richness is still underestimated. An example is the new species described here, Forsterinaria emo n. sp., which is particularly interesting because of an unusual structure discovered in its male genitalia which consists of a bunch of bristle-like processes, composing a fringe-like formation on the dorsum of the tegumen. No similar, homologous structure was found in any congener, nor indeed, in any species of diurnal Lepidoptera. Scanning electron microscope studies revealed that the microstructure of the processes resembles a membrane lining the tegumen. Its function is unknown but two hypotheses are discussed based on a comparative study with other genital structures of butterflies. We argue that it may help stabilizing the partners in the process of mating or it may serve as a 'mating plug', preventing the female from multiple copulations. PMID- 27193408 TI - Susceptibility of Nezara viridula (L.) (Hemiptera: Pentatomidae) Egg Masses of Different Sizes to Parasitism by Trissolcus basalis (Woll.) (Hymenoptera: Platygastridae) in the Field. AB - Egg masses of Nezara viridula (L.) are commonly parasitized by Trissolcus basalis (Woll.), and we investigated the role of size of egg masses on parasitization by T. basalis. Sentinel egg masses were exposed to parasitism in the field for 6-7 days, when they were collected for evaluation of parasitoid emergence. We recorded the number of eggs per egg mass, the number of emerged hosts, and the number of empty and parasitized eggs. We calculated the proportion of attacked host egg masses (DE), the proportion of parasitized eggs per attacked egg mass (PE), and total parasitism (PI). The total number of egg masses exposed to parasitism was 330. The minimum, mean, and maximum egg mass sizes were 25, 75.2, and 111, respectively. DE and PE varied widely between different fields, and they were independent of egg mass size. In 14.2% of all parasitized egg masses, we found simultaneous emergence of T. basalis and N. viridula independently of host egg mass size. PE exhibited low variability compared with PI and DE, which were linearly related. PI and DE values from other field studies are consistent with the linear relationship, suggesting that PI is mostly related to the proportion of the DE. This also suggests that total parasitism is independent of egg mass size, of possible differences in plant species, and T. basalis density and strains. PMID- 27193409 TI - Evaluation of Cold and Thermal Fogging Spraying Methods for Mosquito Control. AB - The efficacy of three pyrethroid insecticides (lambda-cyhalothrin, deltamethrin, and cyphenothrin) in cold (CF) and thermal fogging (TF) applications against caged adults of Culex pipiens Linnaeus were evaluated under hot-dry conditions in Riyadh, Saudi Arabia. The efficacy of CF and TF at different distances from the release point (15, 30, 45, and 60 m) and height (1 and 2 m) was also investigated by evaluating adult mortality after 24 h of exposure. Our data indicated that TF was more efficacious than CF. While the distance from the spray path did not affect TF efficacy, CF showed decreased efficacy with the increase in distance from the spray path. Deltamethrin efficacy was significantly affected by both the application method and distance from the spray path, whereas lambda-cyhalothrin was only affected by the spray method. PMID- 27193410 TI - Resistance of Sugarcane Cultivars to Mahanarva fimbriolata (Stal) (Hemiptera: Cercopidae). AB - The spittlebug Mahanarva fimbriolata (Stal) (Hemiptera: Cercopidae) is one of the most important pests of the sugarcane crop in Brazil. Despite of its importance, there is currently a lack of information regarding sugarcane cultivars' resistance to the spittlebug. Therefore, our objective was to evaluate the response of sugarcane genotypes to this species. Two experiments were carried out under laboratory conditions using a random block design with treatments in a factorial arrangement of 2 * 13 (experiment 1) and 2 * 12 (experiment 2), with six replicates. The first factor included two levels of infestation (infested and noninfested plants with spittlebugs), while the second consisted of the cultivars. Nymph survival varied from 47.9 to 84.5%, indicating that there are different levels of antibiosis to M. fimbriolata among the tested cultivars. The highest degree of antibiosis was found in cultivars IACSP96-7586 and IACSP96 2008, in which nymph survival was close to 48%. IACSP96-7586 also presented some degree of tolerance, but IACSP96-7569 and IACSP97-6682 stood out as the most tolerant cultivars to the pest, showing the lowest reduction in weight of aboveground biomass. On average, spittlebug infestations caused a significant reduction in relative leaf chlorophyll content and aboveground biomass weight. PMID- 27193411 TI - Family Physicians' Knowledge, Attitudes, and Practices Toward Colorectal Cancer Screening. AB - The purpose of this study was to assess family physicians' knowledge, attitudes, and practices toward colorectal cancer (CRC) screening. The population in this cross-sectional study consisted of 290 family physicians working in Samsun, Turkey, contacted between 15 June and 15 July 2015 and agreeing to participate. A questionnaire prepared by the authors on the basis of the relevant literature was applied at face-to-face interviews. The first part of the questionnaire inquired into sociodemographic information, while the second contained questions evaluating family physicians' knowledge, attitudes, and practices toward CRC screening. Physicians completed the questionnaire in approximately 10 min. 65.9 % of the family physicians in the study were men. Mean age of the participants was 43.40 +/- 6.54 years, and mean number of years in service was 18.43 +/- 6.42. The average number of patients seen by physicians on a daily basis was 51-99. CRC screening was performed by 83.1 % of physicians. The fecal occult blood test (FOBT) was recommended at the correct frequency by 30.7 % of physicians and colonoscopy by 11.7 %. A further 68.6 % of physicians followed no CRC guideline. Only 3.8 % of those reporting using a guideline were able to name it. The great majority of physicians in this study apply CRC screening. However, family physicians lack sufficient information concerning the ages at which screening tests should be started and concluded and how frequently they should be performed. They also do not attach sufficient importance to CRC guidelines. This results in excessive demand for screening tests. PMID- 27193412 TI - Barriers to Completing Delayed Breast Reconstruction Following Mastectomy: a Critical Need for Patient and Clinician Education. AB - Rates of breast reconstruction following mastectomy vary widely, and little is known about why women who originally express an interest in breast reconstruction do not receive it. Improved documentation of clinical decision-making is one of the potential benefits of the electronic health record (EHR), and may serve as a tool to enhance patient-centered, clinical outcomes research. The goals of this study were to explore patterns in delayed reconstruction (DR), identify barriers to follow through, and to determine the adequacy of EHR documentation in providing information about decision-making for breast reconstruction. Retrospective EHR review of women undergoing mastectomy, 2008-2012, was conducted in an academic medical center in New England. Data included patient demographics, cancer stage, co-morbidity index, post-mastectomy reconstruction status, and documented decision-making regarding reconstruction. Of 367 women who had undergone a total mastectomy, 219 did not receive immediate reconstruction. Of these, 24.6 % expressed no interest in DR, 21.9 % expressed interest but were still pending the procedure, and 5.9 % had completed DR. Of decision-making regarding breast reconstruction, 47.5 % lacked documentation. Median follow-up was 34 months. Reasons for not following through with DR included poor timing (25 %), indecision (17 %), desired method of reconstruction not available at treating facility (10 %), persistent obesity (8.3 %), continued smoking (4 %), and reason not specified (35 %). Many women do not receive breast reconstruction despite expressing an initial interest in the procedure. Reasons were multi-factorial and the extent of documentation was inconsistent. Further exploration of potential barriers to breast reconstruction as well as opportunities to enhance shared decision-making may serve to improve patient experience and satisfaction following mastectomy. PMID- 27193413 TI - Reflections: Rethinking the Meaning of Competence. PMID- 27193414 TI - Survivorship Challenges and Information Needs after Radiotherapy for Oral Cancer. AB - Oral cancer (OC) treatment can lead to considerable functional impairment, psychological distress, and decrements in quality of life. Given that limited information and support services are available for cancer survivors, many are turning to the Internet. However, little is known about the specific information and service needs of OC survivors. We conducted a descriptive study to (1) characterize the associations between OC survivor functional problems and distress and (2) describe the Internet use of OC survivors, their satisfaction with existing sources of information/support, and their unmet information and service needs. Ninety-three oral cancer survivors completed cross-sectional surveys within 1-year of completing radiotherapy. Clinical levels of distress were 10 % for depression and 16 % for anxiety. Dental health, smell, and range of motion problems were significant (p < .05) determinants of both depression and anxiety symptoms. Eighty-three percent of survivors used the Internet; most used it to obtain health-related information or support. Unmet information needs included how to live a healthy lifestyle after treatment (87 %), strategies for dealing with eating and speaking problems (81 %), and information about what to expect in terms of side effects after treatment (76 %). Findings suggest that interventions that teach survivors coping and problem-solving skills to manage and cope with functional impairments may help to alleviate distress. Results of this study support the need for psychoeducational interventions for this population and showcase the potential of the Internet as a feasible mode for future dissemination. PMID- 27193415 TI - Medication-related adverse events during hospitalization: a retrospective patient record review study in The Netherlands. AB - PURPOSE: Medication-related adverse events (MRAEs) are an important priority for patient safety. Results from Dutch AE studies showed that-despite various improvement initiatives-the incidence of preventable MRAEs did not decline. The aim of this study is to describe the characteristics of MRAEs during hospitalizations using national patient data from records of patients admitted to Dutch hospitals in 2008 and 2011/2012. METHODS: Trained nurses and physicians reviewed the randomly selected records of 8071 patients admitted to one of 20 hospitals in 2008 or 2011/2012 during a two-stage review process. Patient and admission characteristics were collected. After identification of a MRAE, physicians determined their potential preventability, drug type, related prescribing factors, and potential consequences. RESULTS: The physicians identified 928 adverse events (AEs) in 857 admissions, of which 218 (15.2%) were medication-related. They judged 55 (18.4%) of these as preventable. Preventability of MRAEs was high in anticoagulant treatment (42.5%). Haematoma (39.0%) and intra-cerebral haemorrhage (25.5%) were common types of anticoagulant related AEs. Anticoagulant-related AEs were often related to dosage factors (46.9%) and often resulted in an intervention (80.2%), of which 40.2% was judged as preventable. CONCLUSIONS: This study provided detailed information on MRAEs during hospital admissions in The Netherlands. A substantial proportion of AEs was medication-related (15.2%), of which 18.4% was judged to be preventable. As preventability in MRAEs was especially high in anticoagulant treatment (42.5%), those medications are a threat to patient safety. Future research and new safety programs should focus on prevention of AEs related to this medication group. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27193416 TI - Endocannabinoid signaling regulates regenerative axon navigation in Caenorhabditis elegans via the GPCRs NPR-19 and NPR-32. AB - The axon regeneration ability of neurons depends on the interplay of factors that promote and inhibit regeneration. In Caenorhabditis elegans, axon regeneration is promoted by the JNK MAP kinase (MAPK) pathway. Previously, we found that the endocannabinoid anandamide (AEA) inhibits the axon regeneration response of motor neurons after laser axotomy by suppressing the JNK signaling pathway. Here, we show that the G-protein-coupled receptors (GPCRs) NPR-19 and NPR-32 inhibit axon regeneration in response to AEA. Furthermore, we show that sensory neuron expression of the nape-1 gene, which encodes an enzyme synthesizing AEA, causes the regenerating motor axons to avoid sensory neurons and this avoidant response depends on NPR-19 and NPR-32. These results indicate that the navigation of regenerating axons is modulated by the action of AEA on NPR-19/32 GPCRs. PMID- 27193418 TI - Helminth parasites in black rats (Rattus rattus) and brown rats (Rattus norvegicus) from different environments in the Netherlands. AB - BACKGROUND: Rattus norvegicus (brown rat) and Rattus rattus (black rat) are known carriers of bacteria, viruses, and parasites of zoonotic and veterinary importance. Moreover, rats may play a role in the transmission of muscle larvae of the zoonotic nematode Trichinella spiralis to farm animals. We aimed to study the intestinal and intramuscular helminths in wild rats from three different environments to assess the relevance of rats as carrier of zoonotic parasites for public health. MATERIALS AND METHODS: Wild brown rats (117 individuals) and black rats (44 individuals) were captured at farms, in suburban and in rural environments in the Netherlands. Intestinal helminths were isolated and identified morphologically. Artificial digestion was used to isolate muscle larvae. RESULTS AND DISCUSSION: Morphological analysis of rat intestinal contents yielded six nematode species (Syphacia muris, Heterakis spumosa, Aonchotheca murissylvatici, Trichuris muris, Nippostrongylus brasiliensis, and Strongyloides sp.), three cestode species (Hymenolepis diminuta, H. nana and Hymenolepis (=Rodentolepis) fraterna), and four trematode species (Plagiorchis muris, Plagiorchis proximus, Echinostoma chloropodis, and Notocotylus imbricatus).Black rats at farms displayed the lowest intestinal helminth species variation (six species) and carried overall on average 0.93 species simultaneously. In comparison, brown rats at farms carried seven helminth species and 1.91 species simultaneously. Brown rats from suburban environments displayed the highest species variation (11 species) at 1.82 simultaneous helminth species. Absence of trematodes from rats at farms may suggest limited exchange of rats between farms and surrounding wet rural environments. We report four species of veterinary (Syphacia muris) or zoonotic relevance (Hymenolepis diminuta, Hymenolepis nana and Plagiorchis muris). We did not find Trichinella muscle larvae, consistent with long-term prevalence in Dutch wild rats. PMID- 27193417 TI - Superficial Mycoses Associated with Diaper Dermatitis. AB - Diapers create particular conditions of moisture and friction, and with urine and feces come increased pH and irritating enzymes (lipases and proteases). Fungi can take advantage of all these factors. Candida yeasts, especially C. albicans, are responsible for the most frequent secondary infections and are isolated in more than 80 % of cases. Correct diagnosis is important for ensuring the correct prescription of topical antimycotics. Nystatin, imidazoles and ciclopirox are effective. It is important to realize there are resistant strains. Dermatophytes can infect the diaper area, with the most common agent being Epidermophyton floccosum. The clinical characteristics of dermatophytosis are different from those of candidiasis, and it can be diagnosed and treated simply. Malassezia yeasts can aggravate conditions affecting the diaper area, such as seborrheic dermatitis, atopic dermatitis, and inverse psoriasis. Additional treatment is recommended in this case, because they usually involve complement activation and increased specific IgE levels. Erythrasma is a pseudomycosis that is indistinguishable from candidiasis and may also occur in large skin folds. It is treated with topical antibacterial products and some antimycotics. PMID- 27193419 TI - Methicillin resistance gene diversity in staphylococci isolated from captive and free-ranging wallabies. AB - BACKGROUND: Infection with methicillin-resistant staphylococci (MRS) can be life threatening in humans and its presence in animals is a cause for public health concern. The aim of this study was to measure the prevalence of MRS in captive and free-ranging wallabies over a 16-month period in South Australia, Australia. MATERIALS AND METHODS: Eighty-nine purified staphylococcal isolates recovered from 98 captive and free-ranging wallabies' anterior nasal swabs were used in this study. All isolates were tested for the presence of the mecA, mecA1, and mecC genes. Multiplex PCR-directed SCCmec-typing, ccrB-typing, and determination of the minimal inhibitory concentration of oxacillin were performed on mec positive isolates. RESULTS AND DISCUSSION: In total, 11 non-Staphylococcus aureus MRS were isolated from 7 out of 98 animals, corresponding to a 7.1% carriage rate. The SCCmec types I, III, and V were identified by multiplex PCR and sequencing of the ccrB gene. This is the first report of MRS carriage in both captive and free-ranging wallabies in Australia. These data demonstrate a low prevalence of MRS and no association between wallaby captivity status and MRS carriage could be assigned. These animals may act as a reservoir for the exchange of genetic elements between staphylococci. Furthermore, the mecA genes of animal isolates were identical to that found in human MRS strains and thus the possibility of zoonotic transfer must be considered. PMID- 27193421 TI - Integrase strand transferase inhibitors: the preferred antiretroviral regimen in HIV-positive renal transplantation. AB - In the era of antiretroviral therapy, people living with HIV/AIDS live longer and are subject to co-morbidities that affect the general population, such as chronic kidney disease. An increasing number of people living with HIV/AIDS with end stage renal disease are candidates for renal transplantation. Prior experience demonstrated that HIV-positive renal transplant recipients had acceptable survival but graft survival was decreased and rejection rates were increased, possibly due to suboptimal management of immunosuppressive medications in the face of drug interactions with antiretroviral therapy, particularly protease inhibitors and non-nucleoside reverse transcriptase inhibitors. Integrase strand transferase inhibitors are advantageous since they avoid drug-drug interactions with immunosuppressive drugs such as calcineurin inhibitors. We report clinical outcomes of 12 HIV-positive patients who underwent 13 kidney transplantations at our institution between 2000 and 2015. Cumulative survival was 75%, one-year and three-year survival were 100% and 63%. Integrase strand transferase inhibitor based regimens were used in nine patients, of which eight survived. In patients on integrase strand transferase inhibitor, there was 100% graft survival and two had allograft rejection. In contrast, graft failure occurred in three patients on non-integrase strand transferase inhibitor-based regimens. Based on our study findings and on previously published data, we conclude that integrase strand transferase inhibitor-based therapy, preferably instituted prior to transplantation, is the preferred antiretroviral regimen in HIV-positive renal transplantation. PMID- 27193420 TI - Motor Training Promotes Both Synaptic and Intrinsic Plasticity of Layer II/III Pyramidal Neurons in the Primary Motor Cortex. AB - Motor skill training induces structural plasticity at dendritic spines in the primary motor cortex (M1). To further analyze both synaptic and intrinsic plasticity in the layer II/III area of M1, we subjected rats to a rotor rod test and then prepared acute brain slices. Motor skill consistently improved within 2 days of training. Voltage clamp analysis showed significantly higher alpha-amino 3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-d-aspartate (AMPA/NMDA) ratios and miniature EPSC amplitudes in 1-day trained rats compared with untrained rats, suggesting increased postsynaptic AMPA receptors in the early phase of motor learning. Compared with untrained controls, 2-days trained rats showed significantly higher miniature EPSC amplitude and frequency. Paired-pulse analysis further demonstrated lower rates in 2-days trained rats, suggesting increased presynaptic glutamate release during the late phase of learning. One day trained rats showed decreased miniature IPSC frequency and increased paired pulse analysis of evoked IPSC, suggesting a transient decrease in presynaptic gamma-aminobutyric acid (GABA) release. Moreover, current clamp analysis revealed lower resting membrane potential, higher spike threshold, and deeper afterhyperpolarization in 1-day trained rats-while 2-days trained rats showed higher membrane potential, suggesting dynamic changes in intrinsic properties. Our present results indicate dynamic changes in glutamatergic, GABAergic, and intrinsic plasticity in M1 layer II/III neurons after the motor training. PMID- 27193422 TI - Are HIV-positive young black MSM having safer sex than those who are HIV negative? AB - In the United States, young Black men who have sex with men (YBMSM) bear the single largest burden of the HIV/AIDS epidemic. Whether HIV-positive men in this population practice relatively safer sex than their HIV negative counterparts has not been recently investigated. The purpose of this study was to compare selected sexual risk behaviors between YBMSM who are HIV-positive to their HIV-negative counterparts of the same geographic location in the southern US. A convenience sample of 600 YBMSM completed a computer-assisted self-interview in a private area of a clinic dedicated to sexual health. Frequency/prevalence of 16 sexual risk behaviors was compared between men who were HIV-positive and those who were HIV-negative at the time. Bivariate associations were tested in regression models adjusted for age and having a main male sex partner. One-quarter of the sample (25.5%) was HIV-positive at study enrollment. Remarkably few differences in sexual risk behaviors were observed. HIV-positive men were less likely to report recent sex with a woman ( P = .003), and they were more likely to report recent sex with persons known to be HIV-positive ( P < .001). Of 16 assessed outcome measures, these two significant findings represented the only significant differences in the adjusted analyses. YBMSM residing in the southern US may experience high levels of HIV exposure risk or risk of exposing others to HIV. A particularly urgent need exists to improve post-diagnostic HIV prevention efforts for HIV-positive YBMSM. PMID- 27193423 TI - Isolation and characterization of hair follicle stem cells from Arbas Cashmere goat. AB - In this study, highly purified hair follicle stem cells from Arbas Cashmere goat (gHFSCs) were isolated using enzyme digestion and adhesion to type IV collagen. The biological characteristics of the gHFSCs were identified by morphological observation, growth curve, markers assay and differentiation in vitro. The gHFSCs were in small cell size with typical cobblestone morphology, good adhesion and high refractive index. Immunocytochemistry staining showed the cells were expressing Krt15, Krt19, CD34, Itgbeta1 and Krt14. Cell growth curve indicated that cultured gHFSCs had strong proliferation ability. Krt14 and CD34 were high expressed at the mRNA level, respectively, 39.68 and 24.37 times of the Cashmere goat keratinocytes, and krt15 expression was 5.62 times and itgbeta1 expression was 1.81 times higher (p < 0.01). Western blot detected the expression of all the above markers. After osteogenic induction, the cells were positive for Von Kossa staining and expressed Osteocalcin. Sulfated proteoglycans in cartilaginous matrices were positively stained by Alcian blue after chondrogenic induction and COL2A1 was expressed. In myogenic induction, Hoechst 33342 staining evidenced cytoplasm fusion and positive expression of MyoG was detected by immunocytochemistry. PMID- 27193426 TI - D-A-D-type narrow-bandgap small-molecule photovoltaic donors: pre-synthesis virtual screening using density functional theory. AB - A new series of D-A-D-type small-molecule photovoltaic donors are designed and virtually screened before synthesis using time-dependent density functional theory calculations carefully validated against various polymeric and molecular donors. In this series of new design, benzodithiophene is kept as D to achieve the optimum highest-occupied molecular orbital energy level, while thienopyrroledione is initially chosen as A but later replaced by difluorinated benzodiathiazole or its selenide derivative to achieve the optimum band gap. The D-A-D core is end-capped by pyridone units which could not only enhance their self-assembly via hydrogen bonds but also play a role as an acceptor (A') to form an extended A'-D-A-D-A' small-molecule donor. PMID- 27193425 TI - The movement of water and cryoprotectants across the plasma membrane of mammalian oocytes and embryos and its relevance to vitrification. AB - The permeability of the plasma membrane to water and cryoprotectants is one of the most important factors for determining suitable conditions for vitrification of mammalian oocytes and embryos. In mouse oocytes and early stage embryos, water and cryoprotectants move slowly, principally by simple diffusion. In contrast, in morulae (and probably blastocysts), water, glycerol, and ethylene glycerol move rapidly, principally by facilitated diffusion via aquaporin 3, and DMSO moves rapidly via channels other than aquaporin 3. However, propylene glycol moves principally by simple diffusion. In cows and pigs, similar results were obtained. However, in bovine morulae, DMSO moves principally by simple diffusion. In pigs, permeability to water, glycerol, and ethylene glycol increases not at the morula stage but at the blastocyst stage, and increases further at the expanded blastocyst stage. Therefore, in general, the permeability of mammalian oocytes and early stage embryos to water and cryoprotectants is low. Then, at later stages, the permeability to water and some cryoprotectants markedly increases and occurs by facilitated diffusion via channels, although there are some species specific differences. PMID- 27193427 TI - The current topics of surgical pathology of breast cancer in Japan. PMID- 27193428 TI - Editorial: Towards New Approaches in Alzheimer's Research and Alzheimer's Disease. PMID- 27193424 TI - Endogenous and tumour-derived microRNAs regulate cross-presentation in dendritic cells and consequently cytotoxic T cell function. AB - Dendritic cells (DCs) are potent antigen presenting cells (APCs). They are also specialized in the induction of cytotoxic T lymphocyte mediated responses against extracellular antigens, including tumour-specific antigens, by presenting peptide Major Histocompatibility Complex (MHC) I complexes to naive CD8+ T cells in lymphoid tissues, a process called cross-presentation. Emerging evidence suggests that the efficiency of cross-presentation can be influenced by a unique set of microRNAs (miRNAs). Some are differentially expressed in the course of morphological and functional development of DCs while tumorigenic miRNAs (onco miRs) can be delivered to and inserted into DCs via exosomes. The latter reprogram the miRNA repertoire of DCs, transforming them from effective APCs to negative modulators of immunity, ultimately aiding cancers to evade host immunity. On the other hand, endogenous microRNAs can influence cross presentation either positively or negatively. In this review, we discuss the possible mechanisms by which specific miRNAs influence cross-presentation as well as the viability of manipulating the expression of miRNAs that regulate DC cross presentation as a potential cancer immunotherapy intervention. PMID- 27193429 TI - Branched-chain amino acids regulate insulin-like growth factor-binding protein 1 (IGFBP1) production by decidua and influence trophoblast migration through IGFBP1. AB - STUDY QUESTION: Do branched-chain amino acids (BCAAs) influence the migration of human extravillous trophoblast (EVT) cells through changes in insulin-like growth factor-binding protein 1 (IGFBP1) production in decidual cells? STUDY FINDING: Decidua-derived IGFBP1 had a stimulating effect on migration of EVT. WHAT IS KNOWN ALREADY: IGFBP1 is abundantly secreted from human decidual cells and influences trophoblast migration in human placenta of early pregnancy. In hepatic cells, the expression of IGFBP1 is influenced by nutritional status and BCAAs regulate IGFBP1 production. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: This is a laboratory-based study using human decidual cells and trophoblast cells isolated from placental tissue of early pregnancy (n = 50) and grown as primary cultures. Production of IGFBP1 from decidual cells was examined by enzyme-linked immunosorbent assay and immunoblotting after incubation with or without BCAAs. EVT migration was evaluated using the media conditioned by decidual cells. The effect of conditioned media on phosphorylation of focal adhesion kinase (FAK) in EVT was also analyzed by immunoblotting. The same experiments were repeated in the presence of RGD peptide, which inhibits IGFBP1 binding to alpha5beta1 integrin. An EVT migration assay and the immunoblotting of phosphorylated FAK were also conducted with exogenous IGFBP1. The effect of the conditioned media on cytotrophoblast cell number was also assessed using WST-1 in a cell proliferation assay. MAIN RESULTS AND THE ROLE OF CHANCE: Deprivation of BCAAs on decidual cells significantly suppressed IGFBP1 secretion (P < 0.05, versus BCAA+). Exogenous IGFBP1-stimulated EVT migration (P < 0.05) and phosphorylation of FAK (P < 0.05), and the RGD peptide inhibited these effects. EVT migration and phosphorylation of FAK were stimulated by the conditioned media, presumably by IGFBP1 in the media. RGD treatment abrogated the stimulating effects of conditioned media. The conditioned media deprived of BCAAs had suppressive effects on EVT migration (P < 0.05, versus BCAA+) and phosphorylation of FAK (P < 0.05, versus BCAA+). The conditioned media did not affect number of cytotrophoblast cells. LIMITATIONS, REASONS FOR CAUTION: The conclusions are based on in vitro experiments with human decidual cells and trophoblast cells isolated from placental tissue of early pregnancy, and we were unable to ascertain whether these mechanisms actually operate in vivo. We investigated the effect of decidua-derived IGFBP1 on EVT migration, however, we cannot completely rule out the possibility that endogenous IGF could also influence cell migration. WIDER IMPLICATIONS OF FINDINGS: Interruption of the BCAA supply to uterine decidual cells in early pregnancy may suppress EVT migration through reduced IGFBP1 secretion, which may be one of the pathophysiological conditions responsible for pre-eclampsia. LARGE SCALE DATA: None. STUDY FUNDING/ AND COMPETING INTERESTS: All funds were obtained through Kyorin University School of Medicine. The authors have no conflict of interest to declare. PMID- 27193430 TI - Exploring choriocapillaris under reticular pseudodrusen using OCT-Angiography. AB - PURPOSE: To evaluate if choriocapillaris (CC) vessel density and CC decorrelation signal index are compromised in eyes with reticular pseudodrusen (RPD) using optical coherence tomography angiography (OCT-A). METHODS: Decorrelation values in OCT-A CC images of 20 RPD patients were measured in the outer superior and the outer inferior sector of the EDTRS grid and compared to age-matched healthy controls. CC vessel density and CC decorrelation signal index were measured within a 30 MUm and a 10 MUm OCT-A CC slab. CC data were correlated to number of RPD lesions, predominantly present RPD stage, predominantly present RPD type, retinal area affected by RPD and choroidal thickness (CT). RESULTS: CC vessel density and CC decorrelation signal index decreased in correlation to advancing age in healthy subjects particularly in subjects older than 60 years (CC vessel density: 30 MUm: p=0.0019; 10 MUm: p=0.0014; CC decorrelation signal index: 30 MUm: p=0.0005; 10 MUm: p=0.0003). In the RPD group, CC vessel density (outer superior sector, 10 MUm: 98.299) and CC decorrelation signal index (89.07) were significantly reduced compared to controls (99.203, p=0.0002; 98.09, p=0.0010). The number of RPD lesions was correlated to a reduced CC vessel density (30 MUm: p=0.0355) but not to changes in CC decorrelation signal index. No correlations were found between CC parameters and either RPD stage, RPD type, size of RPD affected area or CT. CONCLUSIONS: OCT-A reveals a distinct reduction in CC vessel density and CC decorrelation signal index in eyes affected by RPD, which emphasizes the relevance of the CC layer in RPD pathogenesis. PMID- 27193431 TI - Ability of an intentionally smaller anterior than posterior gap to reduce the sagittal tibial slope in opening wedge high tibial osteotomy. AB - BACKGROUND: We utilized in vivo 3- dimensional (D) computed tomography (CT) to determine whether the preoperatively planned anterior and posterior opening gap heights correlated with the real gaps following opening wedge high tibial osteotomy (HTO), as well as the relationships between anterior and posterior gap heights and change in sagittal tibial slope. METHODS: This prospective study involved 41 patients (41 knees) undergoing navigation HTO for primary medial osteoarthritis. Mechanical axis (MA), weight-bearing line (WBL) ratio, and posterior tibial slope were measured on radiographs preoperatively and after 3 months. The anterior and posterior opening gaps created by osteotomy were measured using in vivo 3D CT and the patients were classified into a larger anterior or posterior gap group. RESULTS: Of the 41 patients, 24 (59 %) had larger anterior and 17 (41 %) had larger posterior gaps. There were no between group differences in preoperative and postoperative slopes, or in change in slope. The correlation between preoperatively planned and postoperative posterior gaps was good, whereas the correlation of anterior gaps was only fair. Bland Altman plots showed poor agreement for both preoperative and postoperative anterior and posterior gaps. The mean systematic difference (bias) was 2.3 mm (p < 0.001) for anterior and -1.0 mm (p = 0.033) for posterior gaps. CONCLUSIONS: Preoperatively calculated opening gaps, which were planned to be larger posteriorly than anteriorly to minimize the change in slope after surgery, did not correspond with postoperative opening gaps on 3D CT. In addition, postoperative tibial slope did not increase, even when the anterior gap was larger than the posterior gap. TRIAL REGISTRATION: TRIAL REGISTRATION NUMBER: KCT0001905 , April 29, 2016. PMID- 27193432 TI - UK Views toward Breastfeeding in Public: An Analysis of the Public's Response to the Claridge's Incident. AB - BACKGROUND: The embarrassment that UK mothers experience when breastfeeding in public has often been cited as a key factor in the decision of the mother to discontinue breastfeeding. There is convincing evidence that many UK residents are not comfortable with women breastfeeding in public; however, little is known about the underlying reasons for this discomfort. OBJECTIVE: This study aimed to assess views on breastfeeding in public in the United Kingdom and to understand why some UK residents object to this practice. METHODS: The comments sections of news media websites and parenting forums were systematically identified and reviewed for statements made in response to an incident widely reported in the British press: a woman was asked to cover up while breastfeeding in public at Claridge's, a London luxury hotel. Of these, 805 comments (73 108 words) met the inclusion criteria and were thematically analyzed. RESULTS: The majority of commenters were supportive of "discreet" breastfeeding in public, but a significant portion felt that breastfeeding in public is always inappropriate. Sexualization of the breast was mainly evoked as something others may experience while viewing a breastfeeding mother, rather than to reflect the commenters' own views. Common justifications cited against breastfeeding in public were onlookers' embarrassment (not knowing where to look) and disgust (at bodily fluids and/or functions). CONCLUSION: Campaigns portraying breastfeeding in public as normal and desirable with a focus on human milk as food rather than a bodily fluid may improve societal acceptance of breastfeeding in public. PMID- 27193433 TI - Comparison of progression to end-stage renal disease requiring dialysis after partial or radical nephrectomy for renal cell carcinoma in patients with severe chronic kidney disease. AB - PURPOSE: We analyzed trends related to surgical approach for renal cell carcinoma (RCC), including partial nephrectomy (PN) or radical nephrectomy (RN), in patients with stage 4 chronic kidney disease (CKD), and identified predictors for postoperative progression to end-stage renal disease (ESRD) requiring permanent dialysis. METHODS: We enrolled patients with stage 4 CKD who underwent surgery for non-metastatic RCC. We compared their characteristics according to surgical approach (PN vs. RN). Moreover, predictors for postoperative progression to requiring permanent dialysis were determined using multivariable analyses. The Charlson comorbidity index (CCI) was adjusted for age. RESULTS: Fifty-one patients (PN 23, RN 28) were evaluated in the present study. Their mean preoperative estimated glomerular filtration rate (eGFR) was 24 ml/min/1.73 m(2), and four patients had a solitary kidney. Three of 23 patients (13 %) who underwent PN progressed to requiring dialysis after surgery after a median 16 months. In contrast, 13 of 28 patients (46 %) who underwent RN developed dialysis immediately after surgery (median 2 days). Patients who underwent PN had lower T stages (T1, PN 100 % vs. RN 50 %, p = 0.004) and smaller tumors (31 mm vs. 65 mm, p < 0.0001) than did those who underwent RN. RN and lower preoperative eGFR significantly predicted progression to requiring dialysis, while tumor size and CCI did not. CONCLUSIONS: PN tended to be selected for patients with lower T stage and smaller tumors in the limited cohort of stage 4 CKD patients. PN had a significant benefit of preventing dialysis in the multivariable analysis. PMID- 27193434 TI - Switching from subcutaneous insulin injection to oral vildagliptin administration in hemodialysis patients with type 2 diabetes: a pilot study. AB - We conducted this pilot study to examine efficacy and safety of switching from subcutaneous injection of insulin to oral administration of a DPP-4 inhibitor, vildagliptin, in type 2 diabetic patients undergoing hemodialysis. Consecutive type 2 diabetic patients on hemodialysis who were switched from insulin to vildagliptin between August 2010 and April 2011 were extracted from the hospital database. In patients whose post-switch increase in glycated albumin (GA) levels was <1.5 % without resuming insulin at least 24 weeks, the switch was defined as efficacious. In patients who resumed insulin therapy due to worsening of glycemic control or in patients whose GA levels increased by 1.5 % or more, the switch was considered inefficacious. To predict patients in whom switch to vildagliptin proved efficacious, receiver-operating characteristic (ROC) analysis and logistic regression analysis were performed. A total of 20 patients were extracted; insulin dose was 12 +/- 4 units/day; levels of GA and HbA1c was 21.0 +/- 3.7 % and 6.5 +/- 0.6 %, respectively. Among them, 11 patients were efficaciously switched to vildagliptin. ROC analysis and logistic analysis showed that patients with a shorter duration of diabetes, as well as lower levels of GA and HbA1c, appeared to have a higher likelihood of successful treatment switches. None of the patients developed hypoglycemic symptoms, ketoacidosis, or serious adverse events. In conclusion, efficacious change from insulin to vildagliptin was possible in approximately a half of type 2 diabetic dialysis patients. Long-term follow-up studies including large number of patients are needed to confirm these results. PMID- 27193436 TI - Effects of mineralocorticoid receptor antagonists on left ventricular mass in chronic kidney disease patients: a systematic review and meta-analysis. AB - BACKGROUND: Mineralocorticoid receptor antagonists (MRAs) are used widely in treatment of heart failure, but their effects on cardiovascular complications and mortality of chronic kidney disease (CKD) are not well known. Thus, we aim to assess such therapeutic effects of MRAs on CKD. METHODS: Electronic literature published in any language until Dec 31, 2015, was systematically searched on PubMed, Embase, and Cochrane Central Register of Controlled Trials. Primary outcome was left ventricular mass (LVM) or LVM index (LVMI), and secondary outcome was all-cause mortality and major adverse cardiovascular events (MACEs). Results of continuous outcomes were pooled using mean difference (MD) and standard mean difference (SMD). Risk ratios (RRs) with 95 % confidence intervals (CIs) were pooled using a random- or fixed-effects model. RESULTS: Totally 12 studies (6 randomized controlled trials with 1003 participants) involving 4935 patients were included. MRA treatment versus non-MRA treatment resulted in a significant change of 0.93 SMD (standard mean difference) in LVM (LVMI), a significant reduction of 22 % in all-cause mortality, a significant reduction of incidence of MACEs (RR 0.65, P = 0.001), significantly higher prevalence rates of hyperkalemia (>5.5 mmol/L), but no significant change in prevalence rates of severe hyperkalemia (>6.0 mmol/L). CONCLUSION: MRA benefits CKD patients in terms of LVMI, all-cause mortality, and MACEs with no incidence of severe hyperkalemia. Nevertheless, the real effects of MRAs on cardiovascular events and mortality as well as their safety in CKD patients should be identified by further studies with prospective and large-sample clinical trials. PMID- 27193435 TI - The importance of success prediction in angioaccess surgery. AB - Access to the circulation is an "Achilles' heel" of chronic hemodialysis. According to the current guidelines, autologous arteriovenous fistula is the best choice available. However, the impossibility of immediate use and the high rate of non-matured fistulas place fistula far from an ideal hemodialysis vascular access. The first attempt at constructing an angioaccess should result in functional access as much as possible. After failed attempts, patients and nephrologists lose their patience and confidence, which results in high percentage of central venous catheter use. Predictive models could help, but clinical judgment still remains crucial. Early referral to the nephrologist and vascular access surgeon, careful preoperative examinations, preparation of patients and duplex sonography mapping of the vessels are very important in the preoperative stage. In the operative stage, it is crucial to understand that angioaccess procedures should not be considered as minor procedures and these operations must be performed by surgeons with demonstrable interest and experience. In the postoperative stage, appropriate surveillance of the maturation process is also important, as well as good cannulation skills of the dialysis staff. The purpose of this review article is to stress the importance of success prediction in order to avoid unsuccessful attempts in angioaccess surgery. PMID- 27193437 TI - Upper urinary tract urothelial carcinoma behaviors in patients with end-stage renal disease after kidney transplantation in Taiwan. AB - PURPOSE: To determine upper urinary tract urothelial carcinoma (UT-UC) behavior in patients with end-stage renal disease (ESRD) after kidney transplantation (KT). METHODS: From 2005 to 2012, 117 ESRD patients with localized UT-UC underwent nephroureterectomy at our institution. We divide these patients into two groups according to having had KT or not. Kaplan-Meier survival plot and multivariate analysis were used to evaluate whether kidney transplantation interfered with the UT-UC outcome. RESULTS: The mean age was younger in ESRD with KT group (p = 0.001), but there was no difference in gender, smoking, or previous bladder cancer history between these two groups. The pathological features were more aggressive in ESRD with KT group compared to those without KT in regard to incidence of carcinoma in situ (p = 0.025) and multifocality (p = 0.001). Kidney transplantation did not interfere with the oncological outcome of UT-UC in ESRD patients. There were no differences in oncological outcome. Five-year metastasis free survival rate was comparable. CONCLUSION: In our sample, for patients with ESRD after kidney transplantation, the postoperative onset of UT-UC was younger and the pathological features were more aggressive. Standard surgical intervention resulted in satisfactory and similar outcome as did ESRD. PMID- 27193438 TI - Influence of volume administration on Doppler-based renal resistive index, renal hemodynamics and renal function in medical intensive care unit patients with septic-induced acute kidney injury: a pilot study. AB - PURPOSE: Impact of volume challenge (VC) on renal hemodynamics and renal function in patients with septic-induced acute kidney injury in addition to transpulmonary thermodilution (TPTD)-derived hemodynamic parameters. METHODS: Systemic hemodynamic parameters derived from TPTD, Doppler-based resistive index (RI) urine output, creatinine and urea levels were obtained before, after and 24 h after VC. RESULTS: Heart rate (p < 0.045), systolic blood pressure (p < 0.030) and mean arterial pressure (p < 0.001) were significantly altered after VC in VC responders compared to baseline immediately after VC but not after 24 h (p = 0.719; p = 0.576; p = 0.435).TPTD-derived cardiac function parameter cardiac index significantly increased after VC (p < 0.001) as well after 24 h (p < 0.02) in the responder group. Stroke volume index also significantly increased after VC (0.033) in responders immediately after VC, but not after 24 h of VC (p < 0.073). No significant changes could be observed in the non-responder group.Renal RI was not significantly different between VC responders and VC non-responders (p = 0.55) immediately after VC and after 24 h (p = 0.65).Creatinine levels in VC responders significantly decreased after 24 h (p < 0.001). Urine output increased from 400 to 542 ml/d in responders, but not statistically significant (p = 0.09). Vasopressor dose in VC responders was statistically significantly lower after 24 h (p < 0.001) compared to baseline. CONCLUSIONS: Responders to VC with septic induced AKI can benefit from an optimized hemodynamic environment. The resistive index to guide fluid therapy for renal hemodynamic management may be limited by the small magnitude of the changes. PMID- 27193440 TI - Endogenous Estrogens, Estrogen Metabolites, and Breast Cancer Risk in Postmenopausal Chinese Women. AB - BACKGROUND: The role of estrogen metabolism in determining breast cancer risk and differences in breast cancer rates between high-incidence and low-incidence nations is poorly understood. METHODS: We measured urinary concentrations of estradiol and estrone (parent estrogens) and 13 estrogen metabolites formed by irreversible hydroxylation at the C-2, C-4, or C-16 positions of the steroid ring in a nested case-control study of 399 postmenopausal invasive breast cancer case participants and 399 matched control participants from the population-based Shanghai Women's Health Study cohort. Odds ratios (ORs) and 95% confidence intervals (CIs) of breast cancer by quartiles of metabolic pathway groups, pathway ratios, and individual estrogens/estrogen metabolites were estimated by multivariable conditional logistic regression. Urinary estrogen/estrogen metabolite measures were compared with those of postmenopausal non-hormone-using Asian Americans, a population with three-fold higher breast cancer incidence rates. All statistical tests were two-sided. RESULTS: Urinary concentrations of parent estrogens were strongly associated with breast cancer risk (ORQ4vsQ1 = 1.94, 95% CI = 1.21 to 3.12, Ptrend = .01). Of the pathway ratios, the 2 pathway:total estrogens/estrogen metabolites and 2-pathway:parent estrogens were inversely associated with risk (ORQ4vsQ1 = 0.57, 95% CI = 0.35 to 0.91, Ptrend = .03, and ORQ4vsQ1 = 0.61, 95% CI = 0.37 to 0.99, Ptrend = .04, respectively). After adjusting for parent estrogens, these associations remained clearly inverse but lost statistical significance (ORQ4vsQ1 = 0.65, 95% CI = 0.39 to 1.06, Ptrend = .12 and ORQ4vsQ1 = 0.76, 95% CI = 0.44 to 1.32, Ptrend = .28). The urinary concentration of all estrogens/estrogen metabolites combined in Asian American women was triple that in Shanghai women. CONCLUSIONS: Lower urinary parent estrogen concentrations and more extensive 2-hydroxylation were each associated with reduced postmenopausal breast cancer risk in a low-risk nation. Markedly higher total estrogen/estrogen metabolite concentrations in postmenopausal United States women (Asian Americans) than in Shanghai women may partly explain higher breast cancer rates in the United States. PMID- 27193439 TI - Effects of magnesium supplementation on electrophysiological remodeling of cardiac myocytes in L-NAME induced hypertensive rats. AB - Hypertension is one of the major risk factors of cardiac hypertrophy and magnesium deficiency is suggested to be a contributing factor in the progression of this complication. In this study, we aimed to investigate the relationship between intracellular free Mg(2+) levels and electrophysiological changes developed in the myocardium of L-NAME induced hypertensive rats. Hypertension was induced by administration of 40 mg/kg of L-NAME for 6 weeks, while magnesium treated rats fed with a diet supplemented with 1 g/kg of MgO for the same period. L-NAME administration for 6 weeks elicited a significant increase in blood pressure which was corrected with MgO treatment; thereby cardiac hypertrophy developing secondary to hypertension was prevented. Cytosolic free magnesium levels of ventricular myocytes were significantly decreased with hypertension and magnesium administration restored these changes. Hypertension significantly decreased the fractional shortening with slowing of shortening kinetics in left ventricular myocytes whereas magnesium treatment was capable of restoring hypertension-induced contractile dysfunction. Long-term magnesium treatment significantly restored the hypertension-induced prolongation in action potentials of ventricular myocytes and suppressed Ito and Iss currents. In contrast, hypertension dependent decrement in intracellular Mg(2+) level did not cause a significant change in L-type Ca(2+) currents, SR Ca(2+) content and NCX activity. Nevertheless, hypertension mediated increase in superoxide anion, hydrogen peroxide and protein oxidation mitigated with magnesium treatment. In conclusion, magnesium administration improves mechanical abnormalities observed in hypertensive rat ventricular myocytes due to reduced oxidative stress. It is likely that, changes in intracellular magnesium balance may contribute to the pathophysiology of chronic heart diseases. PMID- 27193441 TI - A single point in protein trafficking by Plasmodium falciparum determines the expression of major antigens on the surface of infected erythrocytes targeted by human antibodies. AB - Antibodies to blood-stage antigens of Plasmodium falciparum play a pivotal role in human immunity to malaria. During parasite development, multiple proteins are trafficked from the intracellular parasite to the surface of P. falciparum infected erythrocytes (IEs). However, the relative importance of different proteins as targets of acquired antibodies, and key pathways involved in trafficking major antigens remain to be clearly defined. We quantified antibodies to surface antigens among children, adults, and pregnant women from different malaria-exposed regions. We quantified the importance of antigens as antibody targets using genetically engineered P. falciparum with modified surface antigen expression. Genetic deletion of the trafficking protein skeleton-binding protein 1 (SBP1), which is involved in trafficking the surface antigen PfEMP1, led to a dramatic reduction in antibody recognition of IEs and the ability of human antibodies to promote opsonic phagocytosis of IEs, a key mechanism of parasite clearance. The great majority of antibody epitopes on the IE surface were SBP1 dependent. This was demonstrated using parasite isolates with different genetic or phenotypic backgrounds, and among antibodies from children, adults, and pregnant women in different populations. Comparisons of antibody reactivity to parasite isolates with SBP1 deletion or inhibited PfEMP1 expression suggest that PfEMP1 is the dominant target of acquired human antibodies, and that other P. falciparum IE surface proteins are minor targets. These results establish SBP1 as part of a critical pathway for the trafficking of major surface antigens targeted by human immunity, and have key implications for vaccine development, and quantifying immunity in populations. PMID- 27193444 TI - Traumatic Brain Injury in Children: Role of CDRs-PECARN as a Clinical Predictive Resource for Evaluation of Intracranical Lesions and Neuropsychiatric Outcomes. AB - Cranial computed tomography (CT) is considered the gold standard for the diagnosis of traumatic brain injury (TBI). The aim of this study was to evaluate if the clinical decision rules proposed by the Pediatric Emergency Care Applied Research Network (CDRs-PECARN) are really able to identify the patients who do not need cranial CT. This study investigates the neuropsychiatric outcome after TBI according to a pediatric version of the Glasgow Outcome Scale-Extended (GOS-E Peds). We calculated the sensitivity, specificity, negative predictive value (NPV) and positive predictive value of the CDRs-PECARN in 2 age groups. Sensitivity was very high in both groups, and the NPV was very useful for predicting which subjects, of those who presented without CDRs- PECARN, would have a negative cranial CT. We also evaluated the correlations between the GOS-E Peds and Glasgow Coma Scale and between the GOS-E Peds and cranial CT scan. Our study confirms the validation of the PECARN TBI prediction rules as a clinical instrument which can play a significant role in CT decision-making for children with TBI. It also demonstrates that the GOS-E Peds is a valid pediatric outcome scale for children with TBI, despite some important limitations. PMID- 27193443 TI - Shoot- and root-borne cytokinin influences arbuscular mycorrhizal symbiosis. AB - The arbuscular mycorrhizal (AM) symbiosis is functionally important for the nutrition and growth of most terrestrial plants. Nearly all phytohormones are employed by plants to regulate the symbiosis with AM fungi, but the regulatory role of cytokinin (CK) is not well understood. Here, we used transgenic tobacco (Nicotiana tabacum) with a root-specific or constitutive expression of CK degrading CKX genes and the corresponding wild-type to investigate whether a lowered content of CK in roots or in both roots and shoots influences the interaction with the AM fungus Rhizophagus irregularis. Our data indicates that shoot CK has a positive impact on AM fungal development in roots and on the root transcript level of an AM-responsive phosphate transporter gene (NtPT4). A reduced CK content in roots caused shoot and root growth depression following AM colonization, while neither the uptake of phosphorus or nitrogen nor the root transcript levels of NtPT4 were significantly affected. This suggests that root CK may restrict the C availability from the roots to the fungus thus averting parasitism by AM fungi. Taken together, our study indicates that shoot- and root borne CK have distinct roles in AM symbiosis. We propose a model illustrating how plants may employ CK to regulate nutrient exchange with the ubiquitous AM fungi. PMID- 27193445 TI - Molecular identification of iridoviruses infecting various sturgeon species in Europe. AB - Iridoviridae are known to cause disease in sturgeons in North America. Here, histological and molecular methods were used to screen for this family of virus in sturgeons from various European farms with low-to-high morbidity. Some histological samples revealed basophilic cells in the gill and labial epithelia, strongly suggesting the accumulation of iridovirus particles. Newly developed generic PCR tests targeting the major capsid protein (MCP) gene of sturgeon iridoviruses identified in North America, namely the white sturgeon iridovirus and the Namao virus (NV), produced positive signals in most samples from four sturgeon species: Russian (Acipenser gueldenstaedtii), Siberian (A. baerii), Adriatic (A. naccarii) and beluga (Huso huso). The sequences of the PCR products were generally highly similar one another, with nucleotide identities greater than 98%. They were also related to (74-88%), although distinct from, American sturgeon iridoviruses. These European viruses were thus considered variants of a single new virus, provisionally named Acipenser iridovirus-European (AcIV-E). Moreover, three samples infected with AcIV-E showed genetic heterogeneity, with the co-existence of two sequences differing by five nucleotides. One of our European samples carried a virus distinct from AcIV-E, but closely related to NV identified in Canada (95%). This study demonstrates the presence of two distinct sturgeon iridoviruses in Europe: a new genotype AcIV-E and an NV-related virus. PMID- 27193447 TI - Imidazolylpyridine-In(OTf)3 catalyzed enantioselective allylation of ketimines derived from isatins. AB - An enantioselective In(OTf)3-catalyzed allylation of ketimines derived from isatins in the presence of an imidazolylpyridine ligand is described. The reaction proceeded smoothly under mild conditions and resulted in 3-allyl 3 aminooxindoles with good yields and moderate to excellent enantioselectivities (up to 97% ee). PMID- 27193442 TI - Pre-diagnostic meat and fibre intakes in relation to colorectal cancer survival in the European Prospective Investigation into Cancer and Nutrition. AB - Improvements in colorectal cancer (CRC) detection and treatment have led to greater numbers of CRC survivors, for whom there is limited evidence on which to provide dietary guidelines to improve survival outcomes. Higher intake of red and processed meat and lower intake of fibre are associated with greater risk of developing CRC, but there is limited evidence regarding associations with survival after CRC diagnosis. Among 3789 CRC cases in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, pre-diagnostic consumption of red meat, processed meat, poultry and dietary fibre was examined in relation to CRC-specific mortality (n 1008) and all-cause mortality (n 1262) using multivariable Cox regression models, adjusted for CRC risk factors. Pre diagnostic red meat, processed meat or fibre intakes (defined as quartiles and continuous grams per day) were not associated with CRC-specific or all-cause mortality among CRC survivors; however, a marginal trend across quartiles of processed meat in relation to CRC mortality was detected (P 0.053). Pre diagnostic poultry intake was inversely associated with all-cause mortality among women (hazard ratio (HR)/20 g/d 0.92; 95 % CI 0.84, 1.00), but not among men (HR 1.00; 95 % CI 0.91, 1.09) (P for heterogeneity=0.10). Pre-diagnostic intake of red meat or fibre is not associated with CRC survival in the EPIC cohort. There is suggestive evidence of an association between poultry intake and all-cause mortality among female CRC survivors and between processed meat intake and CRC specific mortality; however, further research using post-diagnostic dietary data is required to confirm this relationship. PMID- 27193448 TI - Ionic Conduction in Lithium Ion Battery Composite Electrode Governs Cross sectional Reaction Distribution. AB - Composite electrodes containing active materials, carbon and binder are widely used in lithium-ion batteries. Since the electrode reaction occurs preferentially in regions with lower resistance, reaction distribution can be happened within composite electrodes. We investigate the relationship between the reaction distribution with depth direction and electronic/ionic conductivity in composite electrodes with changing electrode porosities. Two dimensional X-ray absorption spectroscopy shows that the reaction distribution is happened in lower porosity electrodes. Our developed 6-probe method can measure electronic/ionic conductivity in composite electrodes. The ionic conductivity is decreased for lower porosity electrodes, which governs the reaction distribution of composite electrodes and their performances. PMID- 27193446 TI - Single molecule targeted sequencing for cancer gene mutation detection. AB - With the rapid decline in cost of sequencing, it is now affordable to examine multiple genes in a single disease-targeted clinical test using next generation sequencing. Current targeted sequencing methods require a separate step of targeted capture enrichment during sample preparation before sequencing. Although there are fast sample preparation methods available in market, the library preparation process is still relatively complicated for physicians to use routinely. Here, we introduced an amplification-free Single Molecule Targeted Sequencing (SMTS) technology, which combined targeted capture and sequencing in one step. We demonstrated that this technology can detect low-frequency mutations using artificially synthesized DNA sample. SMTS has several potential advantages, including simple sample preparation thus no biases and errors are introduced by PCR reaction. SMTS has the potential to be an easy and quick sequencing technology for clinical diagnosis such as cancer gene mutation detection, infectious disease detection, inherited condition screening and noninvasive prenatal diagnosis. PMID- 27193450 TI - Cancer Stem Cells: Basic Concepts and Therapeutic Implications. AB - Different mechanisms contribute to intratumor heterogeneity, including genetic mutations, the microenvironment, and the existence of subpopulations of cancer cells with increased renewal capacity and the ability to recapitulate the heterogeneity found in primary tumors, which are referred to as cancer stem cells (CSCs). In this review, we discuss how the concept of CSCs has been defined, what assays are currently used to define the functional properties of CSCs, what intrinsic and extrinsic mechanisms regulate CSC functions, how plastic CSCs are, and the importance of epithelial-to-mesenchymal transition in conferring CSC properties. Finally, we discuss the mechanisms by which CSCs may resist medical therapy and contribute to tumor relapse. PMID- 27193449 TI - Discourse, ideas and power in global health policy networks: political attention for maternal and child health in the millennium development goal era. AB - BACKGROUND: Maternal and child health issues have gained global political attention and resources in the past 10 years, due in part to their prominence on the Millennium Development Goal agenda and the use of evidence-based advocacy by policy networks. This paper identifies key factors for this achievement, and raises questions about prospective challenges for sustaining attention in the transition to the post-2015 Sustainable Development Goals, far broader in scope than the Millennium Development Goals. METHODS: This paper relies on participant observation methods and document analysis to develop a case study of the behaviours of global maternal and child health advocacy networks during 2005 2015. RESULTS: The development of coordinated networks of heterogeneous actors facilitated the rise in attention to maternal and child health during the past 10 years. The strategic use of epidemiological and economic evidence by these networks enabled policy attention and promoted network cohesion. The time-bound opportunity of reaching the 2015 Millennium Development Goals created a window of opportunity for joint action. As the new post-2015 goals emerge, networks seek to sustain attention by repositioning their framing of issues, network structures, and external alliances, including with networks that lay both inside and outside of the health domain. CONCLUSIONS: Issues rise on global policy agendas because of how ideas are constructed, portrayed and positioned by actors within given contexts. Policy networks play a critical role by uniting stakeholders to promote persuasive ideas about policy problems and solutions. The behaviours of networks in issue-framing, member-alignment, and strategic outreach can force open windows of opportunity for political attention -- or prevent them from closing. PMID- 27193452 TI - Pathogenesis of Myeloproliferative Disorders. AB - Myeloproliferative neoplasms (MPNs) are a set of chronic hematopoietic neoplasms with overlapping clinical and molecular features. Recent years have witnessed considerable advances in our understanding of their pathogenetic basis. Due to their protracted clinical course, the evolution to advanced hematological malignancies, and the accessibility of neoplastic tissue, the study of MPNs has provided a window into the earliest stages of tumorigenesis. With the discovery of mutations in CALR, the majority of MPN patients now bear an identifiable marker of clonal disease; however, the mechanism by which mutated CALR perturbs megakaryopoiesis is currently unresolved. We are beginning to understand better the role of JAK2(V617F) homozygosity, the function of comutations in epigenetic regulators and spliceosome components, and how these mutations cooperate with JAK2(V617F) to modulate MPN phenotype. PMID- 27193453 TI - The Role of Surgical Pathology in Guiding Cancer Immunotherapy. AB - The recognition that the immune system can identify and destroy tumor cells has driven a paradigm shift in our understanding of human cancer. Therapies designed to enhance this capacity, including cancer vaccines and coinhibitory receptor blockade, have demonstrated clinical efficacy in treating tumors refractory to conventional therapy. In this review, we discuss how the analysis of the immune microenvironment in primary tissue biopsy samples can be used to stratify patients according to clinical outcome, identify patients likely to benefit from specific immunotherapies, and tailor combination immunotherapy to individual patients and tumor types. As immunotherapy gains in complexity and is used in combination with agents that target oncogenic, intracellular signaling pathways, diagnostic pathologists will play an increasingly important part in identifying and quantifying cellular and molecular biomarkers in tissue samples that reflect the nature and magnitude of the antitumor immune response. PMID- 27193454 TI - Obesity, Inflammation, and Cancer. AB - Obesity, a worldwide epidemic, confers increased risk for multiple serious conditions, including cancer, and is increasingly recognized as a growing cause of preventable cancer risk. Chronic inflammation, a well-known mediator of cancer, is a central characteristic of obesity, leading to many of its complications, and obesity-induced inflammation confers additional cancer risk beyond obesity itself. Multiple mechanisms facilitate this strong association between cancer and obesity. Adipose tissue is an important endocrine organ, secreting several hormones, including leptin and adiponectin, and chemokines that can regulate tumor behavior, inflammation, and the tumor microenvironment. Excessive adipose expansion during obesity causes adipose dysfunction and inflammation to increase systemic levels of proinflammatory factors. Cells from adipose tissue, such as cancer-associated adipocytes and adipose-derived stem cells, enter the cancer microenvironment to enhance protumoral effects. Dysregulated metabolism that stems from obesity, including insulin resistance, hyperglycemia, and dyslipidemia, can further impact tumor growth and development. This review describes how adipose tissue becomes inflamed in obesity, summarizes ways these mechanisms impact cancer development, and discusses their role in four adipose-associated cancers that demonstrate elevated incidence or mortality in obesity. PMID- 27193455 TI - Hematopoietic Stem Cell Niche in Health and Disease. AB - Regulation of stem cells in adult tissues is a key determinant of how well an organism can respond to the stresses of physiological challenge and disease. This is particularly true of the hematopoietic system, where demands on host defenses can call for an acute increase in cell production. Hematopoietic stem cells receive the regulatory signals for cell production in adult mammals in the bone marrow, a tissue with higher-order architectural and functional organization than previously appreciated. Here, we review the data defining particular structural components and heterologous cells in the bone marrow that participate in hematopoietic stem cell function. Further, we explore the case for stromal hematopoietic cell interactions contributing to neoplastic myeloid disease. As the hematopoietic regulatory networks in the bone marrow are revealed, it is anticipated that strategies will emerge for how to enhance or inhibit production of specific blood cells. In that way, the control of hematopoiesis will enter the domain of therapies to modulate broad aspects of hematopoiesis, both normal and malignant. PMID- 27193451 TI - Hypoxia and Mucosal Inflammation. AB - Sites of inflammation are defined by significant changes in metabolic activity. Recent studies have suggested that O2 metabolism and hypoxia play a prominent role in inflammation so-called "inflammatory hypoxia," which results from a combination of recruited inflammatory cells (e.g., neutrophils and monocytes), the local proliferation of multiple cell types, and the activation of multiple O2 consuming enzymes during inflammation. These shifts in energy supply and demand result in localized regions of hypoxia and have revealed the important function off the transcription factor HIF (hypoxia-inducible factor) in the regulation of key target genes that promote inflammatory resolution. Analysis of these pathways has provided multiple opportunities for understanding basic mechanisms of inflammation and has defined new targets for intervention. Here, we review recent work addressing tissue hypoxia and metabolic control of inflammation and immunity. PMID- 27193456 TI - Mechanisms of MicroRNAs in Atherosclerosis. AB - The maladaptation of endothelial cells to disturbed flow at arterial bifurcations increases permeability for lipoproteins. Additional injury by chemically modified lipoproteins disrupts the continuous repair of maladapted endothelial cells and triggers intimal macrophage accumulation. Macrophages remove modified lipoproteins from the extracellular space until the cholesterol overload leads to macrophage death and insufficient efferocytosis. This macrophage failure promotes the progression to advanced lesions by formation of a lipid-rich necrotic core, which may rupture and cause myocardial infarction and stroke. In this article, we summarize the fundamental roles of microRNAs (miRNAs) in the regulation of endothelial maladaptation and macrophage failure during atherosclerosis. We describe how miRNAs coordinate the mutual interaction between chronic endothelial repair and endothelial senescence and mechanistically link the regulation of macrophage cholesterol homeostasis with defective efferocytosis. Lastly, we discuss how miRNAs may challenge and extend current theories about atherosclerosis. PMID- 27193458 TI - Inflammatory myofibroblastic tumour of sigmoid mesocolon in a child. PMID- 27193457 TI - Serotype-specific differences in short- and longer-term mortality following invasive pneumococcal disease. AB - Invasive pneumococcal disease (IPD), caused by infection with Streptococcus pneumoniae, has a substantial global burden. There are over 90 known serotypes of S. pneumoniae with a considerable body of evidence supporting serotype-specific mortality rates immediately following IPD. This is the first study to consider the association between serotype and longer-term mortality following IPD. Using enhanced surveillance data from the North East of England we assessed both the short-term (30-day) and longer-term (?7 years) independent adjusted associations between individual serotypes and mortality following IPD diagnosis using logistic regression and extended Cox proportional hazards models. Of the 1316 cases included in the analysis, 243 [18.5%, 95% confidence interval (CI) 16.4-20.7] died within 30 days of diagnosis. Four serotypes (3, 6A, 9N, 19 F) were significantly associated with overall increased 30-day mortality. Effects were observable only for older adults (?60 years). After extension of the window to 12 months and 36 months, one serotype was associated with significantly increased mortality at 12 months (19 F), but no individual serotypes were associated with increased mortality at 36 months. Two serotypes had statistically significant hazard ratios (HR) for longer-term mortality: serotype 1 for reduced mortality (HR 0.51, 95% CI 0.30-0.86) and serotype 9N for increased mortality (HR 2.30, 95% CI 1.29-4.37). The association with serotype 9N was no longer observed after limiting survival analysis to an observation period starting 30 days after diagnosis. This study supports the evidence for associations between serotype and short-term (30-day) mortality following IPD and provides the first evidence for the existence of statistically significant associations between individual serotypes and longer-term variation in mortality following IPD. PMID- 27193459 TI - Clean cut surgery. PMID- 27193460 TI - Do gray wolves (Canis lupus) support pack mates during aggressive inter-pack interactions? AB - For group-living mammals, social coordination increases success in everything from hunting and foraging (Crofoot and Wrangham in Mind the Gap, Springer, Berlin, 2010; Bailey et al. in Behav Ecol Sociobiol 67:1-17, 2013) to agonism (Mosser and Packer in Anim Behav 78:359-370, 2009; Wilson et al. in Anim Behav 83:277-291, 2012; Cassidy et al. in Behav Ecol 26:1352-1360, 2015). Cooperation is found in many species and, due to its low costs, likely is a determining factor in the evolution of living in social groups (Smith in Anim Behav 92:291 304, 2014). Beyond cooperation, many mammals perform costly behaviors for the benefit of group mates (e.g., parental care, food sharing, grooming). Altruism is considered the most extreme case of cooperation where the altruist increases the fitness of the recipient while decreasing its own fitness (Bell in Selection: the mechanism of evolution. Oxford University Press, Oxford 2008). Gray wolf life history requires intra-pack familiarity, communication, and cooperation in order to succeed in hunting (MacNulty et al. in Behav Ecol doi: 10.1093/beheco/arr159 2011) and protecting group resources (Stahler et al. in J Anim Ecol 82: 222-234, 2013; Cassidy et al. in Behav Ecol 26:1352-1360, 2015). Here, we report 121 territorial aggressive inter-pack interactions in Yellowstone National Park between 1 April 1995 and 1 April 2011 (>5300 days of observation) and examine each interaction where one wolf interferes when its pack mate is being attacked by a rival group. This behavior was recorded six times (17.6 % of interactions involving an attack) and often occurred between dyads of closely related individuals. We discuss this behavior as it relates to the evolution of cooperation, sociality, and altruism. PMID- 27193462 TI - [German urologists are open to new ways of making wise decisions]. PMID- 27193461 TI - P-Glycoprotein Activity in Steroid-Responsive vs. Steroid-Resistant Nephrotic Syndrome. AB - OBJECTIVES: To explore the expression of P-glycoprotein (P-gp) in the peripheral blood nucleated cells (PBNCs) of children with nephrotic syndrome in relation to their clinical response to glucocorticoid treatment. METHODS: Thirty-six children with nephrotic syndrome (20 cases of steroid-responsive and 16 cases of steroid resistant) were examined. All the participants were subjected to complete history taking, thorough clinical examination, laboratory investigations (24-h urinary protein, serum albumin, complete blood count with differential white blood cell count, serum cholesterol, serum urea, serum creatinine) and functional assay of P gp using FACS Calibur flowcytometry. P-gp assay was done in both groups during remission. RESULTS: P-gp activity was significantly higher in steroid-resistant than steroid-sensitive cases. CONCLUSIONS: P-gp can be used as a predictor of outcome, as a part of laboratory evaluation of the cases before starting steroid therapy, so as to determine whether to use alternative line of therapy or use one of the P-gp inhibitors with steroid therapy. PMID- 27193463 TI - Disease burden of ischaemic heart disease from short-term outdoor air pollution exposure in Tianjin, 2002-2006. AB - AIMS: To obtain a reliable estimation of the health impact of air pollution, we explored the effects of air pollutants on years of life lost from ischaemic heart disease in Tianjin, China. METHODS AND RESULTS: We conducted a retrospective ecological analysis using daily time series set in six urban districts in Tianjin. Our data included 28,365 ischaemic heart disease deaths registered in 2002-2006. The main outcome measures were years of life lost and deaths from ischaemic heart disease. We found mean concentrations of daily particulate matter with an aerodynamic diameter of less than 10 um in size (PM10), sulfur dioxide and nitrogen dioxide of 125.6 ug/m3, 78.7 ug/m3, 55.1 ug/m3, respectively. Interquartile range increases of PM10, sulfur dioxide and nitrogen dioxide were associated with increases in years of life lost from ischaemic heart disease of 13.8, 4.8 and 22.7 years in single pollutant models, respectively. The effects associated with an interquartile range increase in PM10 were greater in women than men. During the 5 years, there were 27,485 years and 1252 deaths advanced by PM10 pollution over expected rates when daily levels did exceed the World Health Organization air quality guidelines. That is to say, on average, 63.12 hours per person were lost by air pollution in the 5-year period in Tianjin. CONCLUSIONS: Short-term exposure to air pollution has a significant impact on ischaemic heart disease years of life lost and mortality in Tianjin, particularly among women. Air quality improvement has become necessary to protect public health. PMID- 27193464 TI - Current situation and future usage of anticancer drug databases. AB - Cancer is a deadly disease with increasing incidence and mortality rates and affects the life quality of millions of people per year. The past 15 years have witnessed the rapid development of targeted therapy for cancer treatment, with numerous anticancer drugs, drug targets and related gene mutations been identified. The demand for better anticancer drugs and the advances in database technologies have propelled the development of databases related to anticancer drugs. These databases provide systematic collections of integrative information either directly on anticancer drugs or on a specific type of anticancer drugs with their own emphases on different aspects, such as drug-target interactions, the relationship between mutations in drug targets and drug resistance/sensitivity, drug-drug interactions, natural products with anticancer activity, anticancer peptides, synthetic lethality pairs and histone deacetylase inhibitors. We focus on a holistic view of the current situation and future usage of databases related to anticancer drugs and further discuss their strengths and weaknesses, in the hope of facilitating the discovery of new anticancer drugs with better clinical outcomes. PMID- 27193465 TI - Safety and QOL in Patients with Advanced NET in a Phase 3b Expanded Access Study of Everolimus. AB - BACKGROUND/AIMS: An open-label, multi-center, expanded access study was conducted in patients with advanced neuroendocrine tumors (NET) treated with everolimus (10 mg/day) to assess safety and health-related quality of life (HRQOL). METHODS: Of the 246 patients enrolled, 126 have pancreatic NET (pNET) and 120 have non-pNET. Patients continued treatment until disease progression, unacceptable toxicity, death, until commercial availability of everolimus, or May 2012, whichever came first. Adverse events (AEs) were analyzed according to Common Terminology Criteria version 4.0. HRQOL was assessed at baseline, for three 28-day cycles, and then at every three cycles until end of treatment (EOT) with EQ-5D, EORTC QLQ C30, and EORTC QLQ-GINET21 instruments. RESULTS: The most common grade 3 or 4 AEs included hyperglycemia, infections, stomatitis, fatigue, and abdominal pain. In patients with pNET, mean (+/- SD) EQ VAS score remained stable at EOT (baseline, 68.8 +/- 19.9 vs. EOT, 66.5 +/- 20.6) without clinically significant change in QLQ-C30 global health status (change from baseline, - 3.9; n = 86). For patients with non-pNET, a reduction in EQ VAS score (63.9 +/- 19.0 vs. 55.3 +/- 23.0) with clinically significant changes in QLQ-C30 global health status (-13.0; n = 69) was seen by EOT. EQ-5D utility scores remained stable in patients with pNET and a moderate decrease was reported by patients with non-pNET. CONCLUSIONS: The safety profile of everolimus was consistent with the previous studies without adversely affecting HRQOL in pNET. Lower baseline HRQOL scores and more frequent comorbidities might have contributed to the worse outcomes in non-pNET. TRIAL REGISTRATION: EudraCT no. 2010-023032-17. PMID- 27193466 TI - Bone mineral density in patients with mucopolysaccharidosis type III. AB - Mucopolysaccharidosis type III (MPS III) is a neurodegenerative disorder. In MPS III patients, heparan sulfate accumulates in many tissues especially the central nervous system. There are limited data regarding bone involvement in MPS III compared to other MPS types. The aim of this study was to evaluate bone mineral density (BMD) and the prevalence of low bone mass, and to explore the association between BMD, vitamin D levels, bone fracture, and patient characteristics in MPS III. A clinical assessment and interview was held to obtain data about family history, height, weight, body mass index (BMI), nutrition, walking capacity, bone fracture, epilepsy, and medical therapy of 15 patients with MPS III. Height, weight, and BMI z scores were calculated. Laboratory tests including 25 hydroxyvitamin D (25-OH-D) were measured. BMD measurements for the lumbar spine were obtained using dual-energy X-ray absorptiometry (DXA). BMD z scores were adjusted for height-for-age z score (HAZ) to provide correction for height deficits. Lumbar spine BMD z score was low (<-1) in five patients for chronological age and normalized in two of five patients after adjustment for HAZ. Three patients continued to have low BMD; these were older than the other patients and one had a history of long bone fracture. Two of these patients were observed to have lost walking capacity at 10 and 14 years, and the other was walking with support. Six patients had deficient, and three patients had insufficient levels of 25-OH-D. Two osteoporotic patients had significantly lower levels of 25-OH-D. We found that older patients with immobility are at high risk of osteoporosis and bone fracture, and vitamin D deficiencies/insufficiencies are widely seen. We recommend monitoring BMD by DXA and checking vitamin D metabolism to assess low bone mass and fracture risk in older MPS III patients with immobility. PMID- 27193467 TI - Relationship between soy milk intake and radiographic knee joint space narrowing and osteophytes. AB - The purpose of this study was to examine the cross-sectional association between dietary soy milk intake and the prevalence of radiographic knee joint space narrowing (JSN) and osteophytes (OST). Soy milk intake was assessed using a validated semiquantitative food frequency questionnaire and classified into three categories: never, =once a day. JSN and OST were assessed individually based on the Osteoarthritis Research Society International atlas. Multivariable logistic models were used after adjusting for potentially confounding factors. A total of 5764 subjects were included. Both the models suggested a significant inverse association between soy milk intake and OST. In model 1 (adjusted for age, body mass index, and sex), the prevalence of OST decreased in ">=once a day" category (OR 0.52, 95 % CI 0.28-0.98, P = 0.042) and "=once a day" category: OR 0.49, 95 % CI 0.26-0.92, P = 0.026; " 0.05). Subjects in Group II experienced, on average, more blood loss than subjects in Group I, 355.50 ml and 238.90 ml, respectively. CONCLUSION: The use of multi-drug combination may offer significant advantage of reducing patients' mean arterial pressure. However, this has no significant effect on reducing blood loss or surgery time in comparison to sevoflurane alone. PMID- 27193473 TI - Genome-wide identification and comparative analysis of the cation proton antiporters family in pear and four other Rosaceae species. AB - The monovalent cation proton antiporters (CPAs) play essential roles in plant nutrition, development, and signal transduction by regulating ion and pH homeostasis of the cell. The CPAs of plants include the Na(+)/H(+) exchanger, K(+) efflux antiporter, and cation/H(+) exchanger families. However, currently, little is known about the CPA genes in Rosaceae species. In this study, 220 CPA genes were identified from five Rosaceae species (Pyrus bretschneideri, Malus domestica, Prunus persica, Fragaria vesca, and Prunus mume), and 53 of which came from P. bretschneideri. Phylogenetic, structure, collinearity, and gene expression analyses were conducted on the entire CPA genes of pear. Gene expression data showed that 35 and 37 CPA genes were expressed in pear fruit and pollen tubes, respectively. The transcript analysis of some CPA genes under abiotic stress conditions revealed that CPAs may play an important role in pollen tubes growth. The results presented here will be useful in improving understanding of the complexity of the CPA gene family and will promote functional characterization in future studies. PMID- 27193475 TI - Cephalometrics in Stickler syndrome: Objectification of the typical facial appearance. AB - INTRODUCTION: Stickler syndrome is a connective tissue disorder characterized by orofacial, ocular, skeletal and auditory symptoms. The orofacial phenotype mainly consists of midfacial hypoplasia, micrognathia and cleft palate. Large phenotypic variability is evident though. Few studies have tried to substantiate the typical facial appearance in Stickler syndrome patients. METHODS: Molecularly confirmed Stickler patients were invited to undergo cephalometric analysis based on a lateral radiograph in standardized conditions. Angular and linear measurements were performed according to Steiner's and Sassouni's analysis and compared with age- and gender-matched reference values. RESULTS: Thirteen patients aged 10-62y were included, twelve of whom had type 1 Stickler syndrome (COL2A1 mutation) and one type 2 Stickler syndrome (COL11A1 mutation). The position of maxilla and mandible relative to the cranial base was not significantly different from the reference population (S-N-A: p = 0.73, S-N-B: p = 0.43). The mandibular plane and y-axis showed an elevated angle with the cranial base in most patients, although not significant for the total group (S-N to Go-Me: p = 0.20, S-N to S-Gn: p = 0.18). Dental analysis was normal, except for a higher overjet value (p = 0.006) and a higher angle between occlusal plane and Frankfort plane (p = 0.022). CONCLUSION: Cephalometric analysis was not able to thoroughly prove the abnormal facial appearance in Stickler syndrome. The majority of patients had normal dentofacial proportions. The most frequently observed anomaly in our series is a rather short and posteriorly rotated mandible, but clinical variability is high. PMID- 27193476 TI - Radiotherapy for oral cancer decreases the cutaneous expression of host defence peptides. AB - INTRODUCTION: Bacterial resistance against antibiotics has become an increasing challenge in the treatment of cutaneous infections. Consequences can be severe, especially in infected wounds following previous local radiotherapy. Certain endogenous peptide antibiotics, the host defence peptides (HDPs), exhibit broad spectrum antimicrobial activity and promote wound healing. Their use as supplements to conventional antibiotics is a current topic of discussion; however, knowledge of their quantities in healthy and compromised tissue is a prerequisite for such discussion. To date, no data concerning HDP quantities in irradiated skin are available. METHODS: Expression profiles of the genes encoding HDPs, namely human beta-defensin-1 (DEFB1, hBD-1), beta-defensin-2 (DEFB4A, hBD 2), beta-defensin-3 (DEFB103, hBD-3) and S100A7, were assessed in samples of non irradiated and irradiated neck. RESULTS: A reduction in the expression of all of the examined genes was observed in irradiated skin when compared with non irradiated skin (statistically significant in the case of S100A7, P = 0.013). Immunohistochemistry revealed differences in HDP distribution with respect to the epithelial layers. CONCLUSION: The study demonstrates a significant reduction in HDP gene expression in neck skin as a result of radiotherapy. These findings might represent a starting point for novel treatments of cutaneous infections in irradiated patients, such as topical supplementation of synthetic HDP. PMID- 27193477 TI - Is a computer-assisted design and computer-assisted manufacturing method for mandibular reconstruction economically viable? AB - The design and manufacture of patient-specific mandibular reconstruction plates, particularly in combination with cutting guides, has created many new opportunities for the planning and implementation of mandibular reconstruction. Although this surgical method is being used more widely and the outcomes appear to be improved, the question of the additional cost has to be discussed. To evaluate the cost generated by the management of this technology, we studied a cohort of patients treated for mandibular neoplasms. The population was divided into two groups of 20 patients each who were undergoing a 'traditional' freehand mandibular reconstruction or a computer-aided design/computer-aided manufacturing (CAD-CAM) mandibular reconstruction. Data concerning operation time, complications, and days of hospitalisation were used to evaluate costs related to the management of these patients. The mean operating time for the CAD-CAM group was 435 min, whereas that for the freehand group was 550.5 min. The total difference in terms of average time gain was 115.5 min. No microvascular complication occurred in the CAD-CAM group; two complications (10%) were observed in patients undergoing freehand reconstructions. The mean overall lengths of hospital stay were 13.8 days for the CAD-CAM group and 17 days for the freehand group. Finally, considering that the institutional cost per minute of theatre time is ?30, the money saved as a result of the time gained was ?3,450. This cost corresponds approximately to the total price of the CAD-CAM surgery. In conclusion, we believe that CAD-CAM technology for mandibular reconstruction will become a widely used reconstructive method and that its cost will be covered by gains in terms of surgical time, quality of reconstruction, and reduced complications. PMID- 27193478 TI - Is there a correlation between the clinical findings and the radiological findings in chronic maxillary sinus atelectasis? AB - OBJECTIVE: Silent sinus syndrome (SSS) is a clinical syndrome that occurs as a result of chronic maxillary sinus atelectasis (CMA) and is seen with progressive enophthalmos and hypoglobus. The aim of this study was to investigate the correlation between radiological findings and clinical findings in patients with radiologically asymmetrical reduced maxillary sinus volume. MATERIAL AND METHOD: A comparison was made of patients with CMA through evaluation of paranasal sinus computed tomography, magnetic resonance imaging examination of maxillary sinus volume of the CMA side and the contralateral side, thickness of the retroantral fat tissue, infraorbital bone curve, uncinate process lateralisation measurement, middle concha diameter, and calculation of the change in location of the inferior rectus muscle. RESULTS: The study included 16 patients. Although a statistically significant difference was determined between the healthy and the pathological sides in respect to maxillary sinus volume, thickness of the retroantral fat tissue, infraorbital bone curve, uncinate process lateralisation measurement, and middle concha diameter (p = 0.00, p = 0.002, p = 0.020, p = 0.020, p = 0.007), no significant difference was determined in respect to the change in location of the inferior rectus muscle (p = 0.154). A positive correlation was determined between the increase in sulcus depth and maxillary sinus volume and inferior orbital bone curve (p < 0.05). CONCLUSION: In CMA patients suspected of having SSS, radiological maxillary sinus volume analysis, determination of retroantral fat thickness, measurement of the infraorbital bone curve, and measurement of the uncinate process lateralisation can be used as objective tests. However, it should be kept in mind that radiological findings may not always be compatible with the ophthalmological examination findings. PMID- 27193479 TI - Influence of repeat surgery on treatment time in the interdisciplinary management of impacted maxillary canines: A retrospective cohort study. AB - PURPOSE: To evaluate the effect of repeat surgery on treatment time in the interdisciplinary management of impacted maxillary canines. MATERIAL AND METHODS: This retrospective cohort study enrolled patients referred for computed tomographic examination for impacted maxillary canines within a 5-year observational period. The occurrence of repeat surgery was analysed with regard to treatment time, canine location, and surgical exposure technique. RESULTS: A total of 55 patients with 79 impacted maxillary canines were analysed. Of those, 83.6% did not present with complications that would have prompted repeat surgery during their treatment. For patients requiring repeat surgery, time until clinically visible movement of the canine was significantly longer (p < 0.001), whereas time between initial movement and eruption into the oral cavity was significantly shorter (p < 0.001). Overall treatment time did not differ significantly (p = 0.13). An open surgical exposure technique was associated with a significantly lower occurrence of repeat surgeries (p = 0.03). Bilateral impaction of canines significantly prolonged overall treatment time (p = 0.01). CONCLUSIONS: In the event of initial treatment failure during the interdisciplinary management of impacted maxillary canines, repeat surgery should be considered, which has limited effect on overall treatment time. An open surgical exposure technique is preferable. PMID- 27193480 TI - Implant supported dental rehabilitation following segmental mandibular reconstruction- quality of life outcomes of a prospective randomized trial. AB - PURPOSE: The primary objective of this study was to assess the difference in quality of life (QoL) in patients with dental rehabilitation using two or four implant-supported overdentures following segmental mandibulectomy defect reconstruction with fibula free flap. MATERIAL AND METHODS: This prospective, parallel designed, randomized clinical study was conducted with a 1:1 ratio. At baseline, all participants already had fibula flap reconstruction for segmental defects of the mandible and rehabilitation with conventional (non-implant supported) removable partial dentures. The participants were then randomized into two groups. Group I received implant supported overdentures on two implants, and Group II received four implants. QoL outcomes were evaluated using standardized questionnaires (EORTC_QLQ c30, H&N35, OHIP, DSI). Outcomes of treatment were evaluated at 6 months (T1) and 1 year (T2) following rehabilitation. RESULTS: A total of 52 patients were randomized into two treatment groups (26 each). After accounting for the loss to lack of follow-up, 22 patients in Group I and 24 patients in Group II were evaluated for QoL at the end of the study. There was a significant improvement in QoL with implant-assisted dental rehabilitation. However there were no significant differences in QoL between the two-implant and four-implant groups. CONCLUSION: Implant-supported removable overdentures improve QoL outcomes in patients with reconstructed mandibles. This study showed no significant difference in QoL outcomes in patients with two- or four-implant supported removable prostheses. PMID- 27193481 TI - The Good, the Bad, and the Ugly: Professional Perceptions of Jury Decision-making Research Practices. PMID- 27193482 TI - Evaluation of cephalexin failure rates in morbidly obese patients with cellulitis. AB - WHAT IS KNOWN AND OBJECTIVE: Identification of adequate antimicrobial dosing regimens for morbidly obese patients is essential given the simultaneous increase in morbid obesity and cellulitis prevalence in recent years. Insufficient data currently exist to describe the effectiveness of extrapolating traditional antibiotic dosing strategies to morbidly obese patients with cellulitis. The primary objective of this study was to compare therapeutic failure rates in non obese and morbidly obese patients with cellulitis when treated with cephalexin at standard dosing. METHODS: This was a single-centre, retrospective cohort analysis. Adult patients hospitalized or under inpatient observation at a 1265 bed academic medical centre who received cephalexin monotherapy for non-purulent cellulitis from 2005 to 2015 were evaluated for inclusion. Patients were divided into two cohorts based on body mass index (BMI), where BMI <30 kg/m(2) was defined as non-obese and BMI >=40 kg/m(2) as morbidly obese. Patients with critical risk factors for purulent or polymicrobial cellulitis were excluded. The primary outcome, therapeutic failure, was defined as a need for extended or additional antimicrobial therapy, surgical intervention, emergency department visit, or re-hospitalization within two to thirty days after cephalexin initiation. RESULTS AND DISCUSSION: A total of 94 patients (69 non-obese and 25 morbidly obese) met inclusion and exclusion criteria, which was below the estimated sample size needed to reach desired power. The rate of therapeutic failure in the morbidly obese group was similar to the non-obese group (20% vs. 14.5%, P = 0.53). Patients most commonly had extended or additional antibiotics prescribed in response to therapeutic failure with cephalexin. WHAT IS NEW AND CONCLUSION: Cephalexin failure rates for cellulitis did not differ statistically between morbidly obese and non-obese patients. The underpowered nature of this study is a limitation. Until further study with a larger sample size is completed, empiric adjustment of cephalexin dosing based solely on BMI may not be necessary. PMID- 27193483 TI - Iron Alkynyl Helicenes: Redox-Triggered Chiroptical Tuning in the IR and Near-IR Spectral Regions and Suitable for Telecommunications Applications. AB - The combination of a bis-alkynyl-helicene moiety with two iron centers leads to novel electroactive species displaying unprecedented redox-triggered chiroptical switching. Upon oxidation, strong changes of vibrational modes (either local or extended coupled modes) are detected by vibrational circular dichroism and Raman optical activity. Remarkably, the sign of the optical rotation at 1.54 um (that is, at wavelengths typically used for telecommunications) changes upon oxidation while the topology and stereochemistry of the helicene remain unchanged. PMID- 27193485 TI - Quantifying Neuromuscular Fatigue Induced by an Intense Training Session in Rugby Sevens. AB - PURPOSE: To compare the sensitivity of a sprint vs a countermovement-jump (CMJ) test after an intense training session in international rugby sevens players, as well as analyze the effects of fatigue on sprint acceleration. METHODS: Thirteen international rugby sevens players completed two 30-m sprints and a set of 4 repetitions of CMJ before and after a highly demanding rugby sevens training session. RESULTS: Change in CMJ height was unclear (-3.6%; +/-90% confidence limits 11.9%. Chances of a true positive/trivial/negative change: 24/10/66%), while a very likely small increase in 30-m sprint time was observed (1.0%; +/ 0.7%, 96/3/1%). A very likely small decrease in the maximum horizontal theoretical velocity (V0) (-2.4; +/-1.8%, 1/4/95%) was observed. A very large correlation (r = -.79 +/- .23) between the variations of V0 and 30-m-sprint performance was also observed. Changes in 30-m sprint time were negatively and very largely correlated with the distance covered above the maximal aerobic speed (r = -.71 +/- .32). CONCLUSIONS: The CMJ test appears to be less sensitive than the sprint test, which casts doubts on the usefulness of a vertical-jump test in sports such as rugby that mainly involve horizontal motions. The decline in sprint performance relates more to a decrease in velocity than in force capability and is correlated with the distance covered at high intensity. PMID- 27193486 TI - High-Dose Fluoride Induces Apoptosis and Inhibits Ameloblastin Secretion in Primary Rat Ameloblast. AB - The objectives of this study are to establish the in vitro culture system for rat primary ameloblast and to investigate the effects of fluoride on cell viability, apoptosis, and ameloblastin (AMBN) secretion of primary rat ameloblast in vitro. Ameloblast was isolated from the tooth germ of the maxillomandibular molar and cultured in vitro. Cells were treated with NaF at 0.4, 0.8, 1.6, 3.2, and 6.4 mM for 24, 48, and 72 h, respectively. Cell viability was measured by MTT assay and apoptosis was tested by flow cytometry. The activation of Fas ligand (FasL)/Fas pathway was detected using immunoblotting for FasL, Fas, cleaved caspase-8, cleaved caspase-3, and cleaved PARP. Secretion of AMBN in culture medium was measured using ELISA. Primary rat ameloblast was successfully isolated and cultured. The effects of low-dose fluoride on cell viability were bi-phasic, while high-dose fluoride resulted in decreased cell viability uniformly. Fluoride induced ameloblast apoptosis via activation of FasL/Fas signaling pathway and diminished secretion of AMBN by ameloblast. Fluoride could decrease ameloblast viability, induce ameloblast apoptosis via activating FasL/Fas signaling pathway, and reduce AMBN secretion. PMID- 27193484 TI - Structural and functional insights into the E3 ligase, RNF126. AB - RNF126 is an E3 ubiquitin ligase that collaborates with the BAG6 sortase complex to ubiquitinate hydrophobic substrates in the cytoplasm that are destined for proteasomal recycling. Composed of a trimeric complex of BAG6, TRC35 and UBL4A the BAG6 sortase is also associated with SGTA, a co-chaperone from which it can obtain hydrophobic substrates. Here we solve the solution structure of the RNF126 zinc finger domain in complex with the BAG6 UBL domain. We also characterise an interaction between RNF126 and UBL4A and analyse the competition between SGTA and RNF126 for the N-terminal BAG6 binding site. This work sheds light on the sorting mechanism of the BAG6 complex and its accessory proteins which, together, decide the fate of stray hydrophobic proteins in the aqueous cytoplasm. PMID- 27193487 TI - Biomarkers for dementia and mild cognitive impairment in Parkinson's disease. AB - Cognitive decline is one of the most frequent and disabling nonmotor features of Parkinson's disease. Around 30% of patients with Parkinson's disease experience mild cognitive impairment, a well-established risk factor for the development of dementia. However, mild cognitive impairment in patients with Parkinson's disease is a heterogeneous entity that involves different types and extents of cognitive deficits. Because it is not currently known which type of mild cognitive impairment confers a higher risk of progression to dementia, it would be useful to define biomarkers that could identify these patients to better study disease progression and possible interventions. In this sense, the identification among patients with Parkinson's disease and mild cognitive impairment of biomarkers associated with dementia would allow the early detection of this process. This review summarizes studies from the past 25 years that have assessed the potential biomarkers of dementia and mild cognitive impairment in Parkinson's disease patients. Despite the potential importance, no biomarker has as yet been validated. However, features such as low levels of epidermal and insulin-like growth factors or uric acid in plasma/serum and of Abeta in CSF, reduction of cerebral cholinergic innervation and metabolism measured by PET mainly in posterior areas, and hippocampal atrophy in MRI might be indicative of distinct deficits with a distinct risk of dementia in subgroups of patients. Longitudinal studies combining the existing techniques and new approaches are needed to identify patients at higher risk of dementia. (c) 2016 International Parkinson and Movement Disorder Society. PMID- 27193489 TI - In memoriam: Prof. Dr. Edwaldo Eduardo Camargo (1938-2016). PMID- 27193490 TI - Metal complexes with di(N-heterocyclic carbene) ligands bearing a rigid ortho-, meta or para-phenylene bridge. AB - Three novel dinuclear bis-dicarbene silver(i) complexes of general formula [Ag2(MeIm-phenylene-MeIm)2](PF6)2 (Im = imidazol-2-ylidene) were synthesized. The corresponding copper(i) and gold(i) complexes were obtained by transmetalation of the di(N-heterocyclic carbene) ligand from the silver(i) species, and both coordination geometry and stoichiometry are maintained for all three group 11 metals as expected. The photophysical properties of the Ag(i) and Au(i) complexes were also investigated and discussed; in particular the most strongly emitting complex was also studied via DFT calculations. In addition, the ruthenium(ii) and iridium(iii) complexes [RuCl(MeIm-(o-phenylene)-MeIm)(p-cym)](PF6) and [IrClCp*(MeIm-(o-phenylene)-MeIm)](PF6) were prepared and shown to present in these cases a chelating coordination of the di(N-heterocyclic carbene) ligand. PMID- 27193488 TI - Checkpoint Inhibitors and Other Immune Therapies for Hodgkin and Non-Hodgkin Lymphoma. AB - OPINION STATEMENT: Treatment for relapsed/refractory (R/R) Hodgkin and non Hodgkin lymphoma remains challenging. The introduction of rituximab to B cell non Hodgkin lymphoma (B-NHL) treatment significantly improved patients' response rate and survival; however, approximately one third of patients with diffuse large B cell lymphoma, the most common B-NHL subtype, still have a relapse or become refractory after first-line therapy. More recently, antibody therapies and small molecule inhibitors were approved for treating R/R lymphomas; these agents include brentuximab vedotin, ibrutinib, and idelalisib. Immune checkpoint inhibitors and other immune therapies are emerging treatments currently being evaluated in various clinical trials for their efficacy against lymphoid malignancies. Striking results from these treatment modalities have been observed in solid tumors, and evidence is accumulating to support their use in various lymphomas. The most exciting results from immune checkpoint inhibitor therapy have been seen in patients with R/R Hodgkin lymphoma, in whom the overall response rate has reached 60-80 %. Results in NHL are more similar to those seen in other solid malignancies, ranging between 20 and 40 %, depending on the histology. Formal approval of these drugs is being awaited, as are the results of combination therapy with checkpoint inhibitors and other treatment modalities, including conventional chemotherapy, small-molecule inhibitors, and other immune therapies. Although response rates have been promising, attention must be paid to the management of unique immune-related adverse events, which warrant close monitoring in some cases. Identification of biomarkers that predict response or severe adverse events using either the tumor specimen or peripheral blood would aid in selecting patients suited for these types of treatment as well as determining the ideal sequence of treatment within the realm of immune therapies. PMID- 27193492 TI - Integrin beta4 is a major target antigen in pure ocular mucous membrane pemphigoid. AB - Previous studies of ocular mucous membrane pemphigoid (OMMP) have identified several components of the basement membrane zone to be autoantigens, including integrin beta4. However, there are no extensive or definitive reported studies that address this, particularly in pure OMMP. To clarify the major autoantigens in pure OMMP. In this study, we examined sera from 43 pure OMMP patients for both IgG and IgA antibodies using newly developed immunoblotting analyses with a hemidesmosome-rich fraction and various recombinant proteins of integrin alpha6beta4, in addition to our routine immune-serological tests. Using a hemidesmosome-rich fraction, sera from patients with pure OMMP demonstrated reactivity of IgG and/or IgA antibodies to integrin beta4, BP180 and laminin-332. The reactivity of pure OMMP sera to integrin beta4 was further confirmed by immunoblotting using integrin beta4 recombinant proteins. Using concentrated supernatant of HaCaT cells, only one serum sample showed positive IgG and IgA reactivity to LAD-1, the ectodomain of BP180. None of the pure OMMP sera reacted with any autoantigens on immunoblotting using normal human epidermal or dermal extracts, or purified human laminin-332. Integrin beta4 was considered to be the major and specific autoantigen for pure OMMP. The new methods established in this study are useful for detection of various autoantigens, particularly integrin beta4. PMID- 27193491 TI - Long-term outcome following regenerative periodontal treatment of intrabony defects. AB - This study aimed to evaluate the long-term outcome of the regenerative periodontal therapy of an intrabony defect in terms of tooth survival and clinical attachment level (CAL) stability. The association between failure and patient as well as tooth variables was assessed. Treatment records of the patients who received regenerative surgery and re-evaluation at 1-year post surgery were screened. Patient and tooth variables, defect characteristics, and types of treatments were collected. Periodontal parameters were retrieved before regenerative surgery (baseline), 1-year post-surgery, and every visits of supportive periodontal treatment (SPT) until failure, including tooth loss or CAL loss >=2 mm was found. In this study, treatment records from 89 patients were included. These patients continued SPT from 0.5-11.16 years. Of these patients, 92.1 % survived from tooth loss, while 61.8 % survived from CAL loss >=2 mm compared to 1-year post-surgery. At the sites with residual pocket depth <5 mm, patients attending SPT >80 % had a significantly less percentage of teeth with CAL loss >=2 mm compared to 1-year post-surgery than those attending SPT <80 %. However, at the sites with residual pocket depth >=5 mm, no significant difference in the percentage of teeth with CAL loss >=2 mm was found between patients attending SPT >80 % or <80 %. Smoking, patient's compliance, and residual pocket depth after regenerative surgery were significantly associated with tooth loss. However, these factors were not significantly associated with CAL loss compared to baseline or 1-year post-surgery. PMID- 27193493 TI - Characterization of Kidney and Skeleton Phenotypes of Mice Double Heterozygous for Foxc1 and Foxc2. AB - Foxc1 and Foxc2 play key roles in mouse development. Foxc1 mutant mice develop duplex kidneys with double ureters, and lack calvarial and sternal bones. Foxc2 null mice have been reported to have glomerular abnormalities in the kidney and axial skeletal anomalies. Expression patterns of Foxc1 and Foxc2 overlap extensively and are believed to have interactive roles. However, cooperative roles of these factors in glomerular and skeletal development are unknown. Therefore, we examined the kidneys and skeleton of mice that were double heterozygous for Foxc1 and Foxc2. Double heterozygotes were generated by mating single heterozygotes for Foxc1 and Foxc2. Newborn double heterozygous mice showed many anomalies in the kidney and urinary tract resembling Foxc1 phenotypes, including duplex kidneys, double ureters, hydronephrosis and mega-ureter. Some mice had hydronephrosis alone. In addition to these macroscopic anomalies, some mice had abnormal glomeruli and disorganized glomerular capillaries observed in Foxc2 phenotypes. Interestingly, these mice also showed glomerular cysts not observed in the single-gene knockout of either Foxc1 or Foxc2 but observed in conditional knockout of Foxc2 in the kidney. Serial section analysis revealed that all cystic glomeruli were connected to proximal tubules, precluding the possibility of atubular glomeruli resulting in cyst formation. Dorsally opened vertebral arches and malformations of sternal bones in the double heterozygotes were phenotypes similar to Foxc1 null mice. Absent or split vertebral bodies in the double heterozygotes were phenotypes similar to Foxc2 null mice, whilst hydrocephalus noted in the Foxc1 phenotype was not observed. Thus, Foxc1 and Foxc2 have a role in kidney and axial skeleton development. These transcription factors might interact in the regulation of the embryogenesis of these organs. PMID- 27193496 TI - Indocyanine Green Fluorescence Navigation Thoracoscopic Metastasectomy for Pulmonary Metastasis of Hepatocellular Carcinoma. AB - Indocyanine green can selectively accumulate in primary hepatocellular carcinoma (HCC) and extrahepatic metastases. We report a patient who underwent resection of pulmonary metastasis of HCC using a thoracoscopic near-infrared imaging system and fluorescent navigation surgery. A 66-year-old man with suspicion of pulmonary metastasis of HCC was referred to our hospital. Indocyanine green was injected intravenously at a dose of 0.5 mg/kg body weight, 20 h before thoracoscopic surgery. An endoscopic indocyanine green near-infrared fluorescence imaging system showed clear blue fluorescence, indicating pulmonary metastasis of HCC in a lingular segment. We performed wide wedge resection using the fluorescence image for navigation to confirm the surgical margins. The specimen was histologically confirmed as a pulmonary metastasis of HCC. In conclusion, thoracoscopic indocyanine green near-infrared fluorescence imaging for pulmonary metastases of HCC is useful in identifying tumor locations and ensuring resection margins. PMID- 27193497 TI - Short-term ubiquinol supplementation reduces oxidative stress associated with strenuous exercise in healthy adults: A randomized trial. AB - Studies about Coenzyme Q10 (CoQ10 ) supplementation on strenuous exercise are scarce, especially those related with oxidative stress associated with physical activity and virtually nonexistent with the reduced form, Ubiquinol. The objective of this study was to determine, for the first time, whether a short term supplementation with Ubiquinol can prevent oxidative stress associated to strenuous exercise. The participants (n = 100 healthy and well trained, but not on an elite level) were classified in two groups: Ubiquinol (experimental group), and placebo group (control). The protocol consisted of conducting two identical strenuous exercise tests with a rest period between tests of 24 h. Blood and urine samples were collected from the participants before supplementation (basal value) (T1), after supplementation (2 weeks) (T2), after first physical exercise test (T3), after 24 h of rest (T4), and after second physical exercise test (T5).The increase observed in the lactate, isoprostanes, DNA damage, and hydroperoxide levels reveals the severity of the oxidative damage induced by the exercise. There was a reduction in the isoprostanes, 8-OHdG, oxidized LDL, and hydroperoxydes in the supplemented Ubiquinol group, an increase in total antioxidant status, fat soluble antioxidant (both plasma and membrane), and CAT activity. Also, NO in the Ubiquinol-supplemented group was maintained within a narrow range. Oxidative stress induced by strenuous exercise is accumulative and increases transiently in subsequent sessions of physical activity. A short-term supplementation (2 weeks) with Ubiquinol (200 mg/day) before strenuous exercise, decreases oxidative stress and increases plasma NO, fact that could improve endothelial function, energetic substrate supply, and muscle recovery after strenuous exercise. (c) 2016 BioFactors, 42(6):612-622, 2016. PMID- 27193498 TI - Expandable Scaffold Improves Integration of Tissue-Engineered Cartilage: An In Vivo Study in a Rabbit Model. AB - One of the major limitations of tissue-engineered cartilage is poor integration of chondrocytes and scaffold structures with recipient tissue. To overcome this limitation, an expandable scaffold with a honeycomb-like structure has been developed using microfluidic technology. In this study, we evaluated the performance of this expandable gelatin scaffold seeded with rabbit chondrocytes in vivo. The chondrocyte/scaffold constructs were implanted into regions of surgically introduced cylindrical osteochondral defects in rabbit femoral condyles. At 2, 4, and 6 months postsurgery, the implanted constructs were evaluated by gross and histological examinations. As expected, the osteochondral defects, which were untreated or transplanted with blank scaffolds, showed no signs of repair, whereas the defects transplanted with chondrocyte/scaffold constructs showed significant cartilage regeneration. Furthermore, the expandable scaffolds seeded with chondrocytes had more regenerated cartilage tissue and better integration with the recipient tissue than autologous chondrocyte implantation. Biomechanical tests revealed that the chondrocyte/scaffold group had the highest compressive strength among all groups at all three time points and endured a similar compressive force to normal cartilage after 6 months of implantation. Histological examinations revealed that the chondrocytes were distributed uniformly within the scaffolds, maintained a normal phenotype, and secreted functional components of the extracellular matrix. Histomorphometric assessment showed a remarkable total interface of up to 87% integration of the expandable scaffolds with the host tissue at 6 months postoperation. In conclusion, the expandable scaffolds improved chondrocyte/scaffold construct integration with the host tissue and were beneficial for cartilage repair. PMID- 27193500 TI - Covalent non-fused tetrathiafulvalene-acceptor systems. AB - Covalent donor-acceptor (D-A) systems have significantly contributed to the development of many organic materials and to molecular electronics. Tetrathiafulvalene (TTF) represents one of the most widely studied donor precursors and has been incorporated into the structure of many D-A derivatives with the objective of obtaining redox control and modulation of the intramolecular charge transfer (ICT), in order to address switchable emissive systems and to take advantage of its propensity to form regular stacks in the solid state. In this review, we focus on the main families of non-fused TTF acceptors, which are classified according to the nature of the acceptor: nitrogen containing heterocycles, BODIPY, perylenes and electron poor unsaturated hydrocarbons, as well as radical acceptors. We describe herein the most representative members of each family with a brief mention of their synthesis and a special focus on their D-A characteristics. Special attention is given to ICT and its modulation, fluorescence quenching and switching, photoconductivity, bistability and spin distribution by discussing and comparing spectroscopic and electrochemical features, photophysical properties, solid-state properties and theoretical calculations. PMID- 27193495 TI - A cure for the blues: opsin duplication and subfunctionalization for short wavelength sensitivity in jewel beetles (Coleoptera: Buprestidae). AB - BACKGROUND: Arthropods have received much attention as a model for studying opsin evolution in invertebrates. Yet, relatively few studies have investigated the diversity of opsin proteins that underlie spectral sensitivity of the visual pigments within the diverse beetles (Insecta: Coleoptera). Previous work has demonstrated that beetles appear to lack the short-wavelength-sensitive (SWS) opsin class that typically confers sensitivity to the "blue" region of the light spectrum. However, this is contrary to established physiological data in a number of Coleoptera. To explore potential adaptations at the molecular level that may compensate for the loss of the SWS opsin, we carried out an exploration of the opsin proteins within a group of beetles (Buprestidae) where short-wave sensitivity has been demonstrated. RNA-seq data were generated to identify opsin proteins from nine taxa comprising six buprestid species (including three male/female pairs) across four subfamilies. Structural analyses of recovered opsins were conducted and compared to opsin sequences in other insects across the main opsin classes-ultraviolet, short-wavelength, and long-wavelength. RESULTS: All nine buprestids were found to express two opsin copies in each of the ultraviolet and long-wavelength classes, contrary to the single copies recovered in all other molecular studies of adult beetle opsin expression. No SWS opsin class was recovered. Furthermore, the male Agrilus planipennis (emerald ash borer EAB) expressed a third LWS opsin at low levels that is presumed to be a larval copy. Subsequent homology and structural analyses identified multiple amino acid substitutions in the UVS and LWS copies that could confer short-wavelength sensitivity. CONCLUSIONS: This work is the first to compare expressed opsin genes against known electrophysiological data that demonstrate multiple peak sensitivities in Coleoptera. We report the first instance of opsin duplication in adult beetles, which occurs in both the UVS and LWS opsin classes. Through structural comparisons of known insect opsins, we suggest that opsin duplication and amino acid variation within the chromophore binding pocket explains sensitivity in the short-wavelength portion of the visible light spectrum in these species. These findings are the first to reveal molecular complexity of the color vision system within beetles. PMID- 27193501 TI - Implementing a culturally appropriate birthing policy: Ethnographic analysis of the experiences of skilled birth attendants in Peru. AB - Policies about skilled birth attendants (SBA) need to account for cultural acceptability of care rendered by SBAs. Few studies have assessed these policies from the perspective of SBAs. I identify challenges and analyze the experiences of SBAs implementing a culturally appropriate birth care policy in Peru. I collected data during 15 months of ethnographic research: conducting semi structured interviews and informal conversations with 5 SBAs in 2 villages and with health officials. I compared interview results with my observations of consultations and of labor and delivery. Weak institutional support, lack of training, negative perceptions of the policy inhibited implementation, as did detrimental effects on future personal and professional opportunities. SBAs in Peru face many challenges when trying to establish intercultural birth care. My recommendations include provision of focused training, promoting a more diverse workforce, and increasing community engagement.Journal of Public Health Policy advance online publication, 19 May 2016; doi:10.1057/jphp.2016.19. PMID- 27193502 TI - A review of health literacy: Definitions, interpretations, and implications for policy initiatives. AB - Definitions and interpretations of 'health literacy' have important implications for the delivery of health care and for health policy-related initiatives. We conducted a systematic review and critical analysis to determine the extent to which definitions of health literacy differ in the academic literature, the similarities and differences across definitions, and possible interpretations for the most commonly used definitions. We identified 250 different definitions of health literacy and grouped them into three categories: (i) most commonly used definitions (n=6), (ii) modified versions of these most commonly used definitions (n=133), and (iii) 'other' definitions (n=111). We found the most commonly used definitions to be open to multiple interpretations and to reflect underlying assumptions that are not always justifiable. Attention is needed to the ways in which differing definitions and interpretations of health literacy may affect patient care and the delivery of health literacy-related policy initiatives.Journal of Public Health Policy advance online publication, 19 May 2016; doi:10.1057/jphp.2016.18. PMID- 27193499 TI - Rapid Inhibition Profiling in Bacillus subtilis to Identify the Mechanism of Action of New Antimicrobials. AB - Increasing antimicrobial resistance has become a major public health crisis. New antimicrobials with novel mechanisms of action (MOA) are desperately needed. We previously developed a method, bacterial cytological profiling (BCP), which utilizes fluorescence microscopy to rapidly identify the MOA of antimicrobial compounds. BCP is based upon our discovery that cells treated with antibiotics affecting different metabolic pathways generate different cytological signatures, providing quantitative information that can be used to determine a compound's MOA. Here, we describe a system, rapid inhibition profiling (RIP), for creating cytological profiles of new antibiotic targets for which there are currently no chemical inhibitors. RIP consists of the fast, inducible degradation of a target protein followed by BCP. We demonstrate that degrading essential proteins in the major metabolic pathways for DNA replication, transcription, fatty acid biosynthesis, and peptidoglycan biogenesis in Bacillus subtilis rapidly produces cytological profiles closely matching that of antimicrobials targeting the same pathways. Additionally, RIP and antibiotics targeting different steps in fatty acid biosynthesis can be differentiated from each other. We utilize RIP and BCP to show that the antibacterial MOA of four nonsteroidal anti-inflammatory antibiotics differs from that proposed based on in vitro data. RIP is a versatile method that will extend our knowledge of phenotypes associated with inactivating essential bacterial enzymes and thereby allow for screening for molecules that inhibit novel essential targets. PMID- 27193503 TI - Nickel-Catalyzed Alkylative Cross-Coupling of Anisoles with Grignard Reagents via C-O Bond Activation. AB - We report nickel-catalyzed cross-coupling of methoxyarenes with alkylmagnesium halides, in which a methoxy group is eliminated. A wide range of alkyl groups, including those bearing beta-hydrogens, can be introduced directly at the ipso position of anisole derivatives. We demonstrate that the robustness of a methoxy group allows this alkylation protocol to be used to synthesize elaborate molecules by combining it with traditional cross-coupling reactions or oxidative transformation. The success of this method is dependent on the use of alkylmagnesium iodides, but not chlorides or bromides, which highlights the importance of the halide used in developing catalytic reactions using Grignard reagents. PMID- 27193504 TI - Highly conformal fabrication of nanopatterns on non-planar surfaces. AB - While the number of techniques for patterning materials at the nanoscale exponentially increases, only a handful of methods approach the conformal patterning of strongly non-planar surfaces. Here, using the direct surface self assembly of colloids by electrostatics, we produce highly conformal bottom-up nanopatterns with a short-range order. We illustrate the potential of this approach by devising functional nanopatterns on highly non-planar substrates such as pyramid-textured silicon substrates and inherently rough polycrystalline films. We further produce functionalized polycrystalline thin-film silicon solar cells with enhanced optical performance. The perspective presented here to pattern essentially any surface at the nanoscale, in particular surfaces with high inherent roughness or with microscale features, opens new possibilities in a wide range of advanced technologies from affordable photovoltaics and optoelectronics to cellular engineering. PMID- 27193506 TI - Potential human health risk assessment of trace metals via the consumption of marine fish in Persian Gulf. AB - This study was carried out to evaluate the concentration of trace metals (Cd, Cu, Ni, Pb and Zn) in the muscle of four fish species from the Persian Gulf. Trace metals were analyzed using atomic absorption spectroscopy and consumption rates advisory for minimizing chronic systemic effects in children and adults were estimated. The metals concentrations in analyzed fish samples were lower than legal limits. Cadmium target hazard quotient values suggested that the threshold to avoid the potential risk for children health is an exposure level lower than 3 meals per week. Hazard index values based on four metals (not including Pb) for the child age class were higher than those of the adult age class, suggesting that children may suffer from a higher health risk. This study provides information about the consumption limits of certain metals, in particular Cd, necessary for minimizing potential health risks resulting from human consumption. PMID- 27193505 TI - Synthesis, antimicrobial and anticonvulsant screening of small library of tetrahydro-2H-thiopyran-4-yl based thiazoles and selenazoles. AB - Synthesis and investigation of antimicrobial activity of 22 novel thiazoles and selenazoles derived from dihydro-2H-thiopyran-4(3H)-one are presented. Additionally, anticonvulsant activity of six derivatives is examinated. Among the derivatives, compounds 4a-f, 4i, 4k, 4 l, 4n, 4o-s and 4v have very strong activity against Candida spp. with MIC = 1.95-15.62 MUg/ml. In the case of compounds 4a-f, 4i, 4k, 4 l, 4n, 4o, 4r and 4s, the activity is very strong against some strains of Candida spp. isolated from clinical materials, with MIC = 0.98 to 15.62 MUg/ml. Additionally, compounds 4n-v are found to be active against Gram-positive bacteria with MIC = 7.81-62.5 MUg/ml. The results of anticonvulsant screening reveal that compounds 4a, 4b, 4m and 4n demonstrate a statistically significant anticonvulsant activity in the pentylenetetrazole model, whereas compounds 4a and 4n showed protection in 6-Hz psychomotor seizure model. Noteworthy, none of these compounds impaired animals' motor skills in the rotarod test. We also performed quantum chemical calculation of interaction and binding energies in complex of 4a with cyclodextrin. PMID- 27193507 TI - Nano-electro-mechanical pump: Giant pumping of water in carbon nanotubes. AB - A fully controllable nano-electro-mechanical device that can pump fluids at nanoscale is proposed. Using molecular dynamics simulations, we show that an applied electric field to an ion@C60 inside a water-filled carbon nanotube can pump water with excellent efficiency. The key physical mechanism governing the fluid pumping is the conversion of electrical energy into hydrodynamic flow with efficiencies as high as 64%. Our results show that water can be compressed up to 7% higher than its bulk value by applying electric fields. High flux of water (up to 13,000 molecules/ns) is obtained by the electro-mechanical, piston-cylinder like moving mechanism of the ion@C60 in the CNT. This large flux results from the piston-like mechanism, compressibility of water (increase in density of water due to molecular ordering), orienting dipole along the electric field and efficient electrical to mechanical energy conversion. Our findings can pave the way towards efficient energy conversion, pumping of fluids at nanoscale, and drug delivery. PMID- 27193509 TI - Under-Liquid Self-Assembly of Submerged Buoyant Polymer Particles. AB - The self-assembly of submerged cold-plasma-treated polyethylene beads (PBs) is reported. The plasma-treated immersed millimetrically sized PBs formed well ordered 2D quasicrystalline structures. The submerged floating of "light" (buoyant) PBs is possible because of the energy gain achieved by the wetting of the high-energy plasma-treated polymer surface prevailing over the energy loss due to the upward climb of the liquid over the beads. The capillary "immersion" attraction force is responsible for the observed self-assembly. The observed 2D quasicrystalline structures demonstrate "dislocations" and "point defects". The mechanical vibration of self-assembled rafts built of PBs leads to the healing of point defects. The immersion capillary lateral force governs the self-assembly, whereas the elastic force is responsible for the repulsion of polymer beads. PMID- 27193508 TI - Intraprocedural balloon dilation of the direct flow medical transcatheter aortic valve: First United States experience. AB - Optimization of hemodynamics during transcatheter aortic valve replacement (TAVR) using the commercially available balloon expandable and self-expanding valves is often accomplished through post-dilation of the valves' metallic frame. The direct flow medical (DFM) valve is a uniquely designed second-generation TAVR prosthetic without a rigid metallic frame. It is not widely known whether balloon dilation of this valve is beneficial when valve hemodynamics after initial deployment suboptimal due to valve underexpansion. We present the first two US patients who underwent TAVR using the DFM valve who had underexpansion in the setting of bulky leaflet calcification that resulted in elevated valve gradients and were treated successfully using intraprocedural balloon dilation. (c) 2016 Wiley Periodicals, Inc. PMID- 27193511 TI - Triboluminescence dominated by crystallographic orientation. AB - Triboluminescence (TL) is an optical phenomenon that has a long and varied history with broad applications, such as damage detection, X-ray source, and mass health monitoring sensor. So far, the properties and mechanisms of TL remain not completely understood. The TL properties emitted during the sliding contact between Al2O3 and SiO2 surfaces were studied along different crystallographic orientations. In this study, the TL intensity of Al2O3 was significantly enhanced as Al2O3 surface was along a particular crystallographic orientation, which is an unconventional phenomenon. TL enhancement of Al2O3 was not affected by air atmosphere and atomic stocking mode of Al2O3. The enhancement mechanism of Al2O3 may be influenced by the surface state of Al2O3. This work provides a new method to control the intensity of TL and novel ideas to elucidate the TL mechanism. PMID- 27193510 TI - Dermal adipocytes' claim for fame in psoriasis. PMID- 27193513 TI - Revealing oxidative damage to enzymes of carbohydrate metabolism in yeast: An integration of 2D DIGE, quantitative proteomics, and bioinformatics. AB - Clinical usage of lidocaine, a pro-oxidant has been linked with severe, mostly neurological complications. The mechanism(s) causing these complications is independent of the blockade of voltage-gated sodium channels. The budding yeast Saccharomyces cerevisiae lacks voltage-gated sodium channels, thus provides an ideal system to investigate lidocaine-induced protein and pathway alterations. Whole-proteome alterations leading to these complications have not been identified. To address this, S. cerevisiae was grown to stationary phase and exposed to an LC50 dose of lidocaine. The differential proteomes of lidocaine treatment and control were resolved 6 h post exposure using 2D DIGE. Amine reactive dyes and carbonyl reactive dyes were used to assess protein abundance and protein oxidation, respectively. Quantitative analysis of these dyes (? 1.5 fold alteration, p ? 0.05) revealed a total of 33 proteoforms identified by MS differing in abundance and/or oxidation upon lidocaine exposure. Network analysis showed enrichment of apoptotic proteins and cell wall maintenance proteins, while the abundance of proteins central to carbohydrate metabolism, such as triosephosphate isomerase and glyceraldehyde-3-phosphate dehydrogenase, and redox proteins superoxide dismutase and peroxiredoxin were significantly decreased. Enzymes of carbohydrate metabolism, such as phosphoglycerate kinase and enolase, the TCA cycle enzyme aconitase, and multiple ATP synthase subunits were found to be oxidatively modified. Also, the activity of aconitase was found to be decreased. Overall, these data suggest that toxic doses of lidocaine induce significant disruption of glycolytic pathways, energy production, and redox balance, potentially leading to cell malfunction and death. PMID- 27193514 TI - Clinically-oriented proteomic investigation of sickle cell disease: Opportunities and challenges. AB - Sickle cell disease (SCD) is an autosomal recessively inherited beta hemoglobinopathy causing a sickling hemoglobin (HbS) to be expressed in the erythrocyte. Due its unique biophysical properties and tendency to form polymers in deoxygenated conditions, HbS causes dramatic erythrocyte deformation and damage ultimately leading to diffuse hemolysis, vasco-occlusion, and vasculopathy in affected individuals. Albeit SCD was the first molecular disease identified in the human several decades ago, the progress in caring for patients with SCD has been globally limited and faces considerable biological, medical, psychological, and economic challenges. The aim of this review is to illustrate the opportunities lying ahead for proteomic discovery in SCD. It also establishes a tentative conceptual framework for clinically oriented investigations. The ultimate target is the translation of findings into validated and actionable improvements at the bedside. Thanks to significant technological advances, proteomics is poised to play an important role for patients affected by hematological disorders, and SCD could be a paradigm for impactful research. PMID- 27193512 TI - Improving the uptake of pre-travel health advice amongst migrant Australians: exploring the attitudes of primary care providers and migrant community groups. AB - BACKGROUND: Migrant travellers who return to their country of origin to visit family and friends (VFR) are less likely to seek travel-related medical care and are less likely to adhere to recommended medications and travel precautions. Through this study, we aimed to get an understanding of the views of stakeholders from community migrant centres and primary care providers on barriers for migrants, particularly from non-English speaking backgrounds, in accessing travel health advice and the strategies that could be used to engage them. METHODS: A qualitative study involving 20 semi-structured interviews was undertaken in Sydney, Australia between January 2013 and September 2014. Thematic analysis was undertaken. RESULTS: Language barriers, a lower perceived risk of travel-related infections and the financial costs of seeking pre-travel health care were nominated as being the key barriers impacting on the uptake of pre-travel health advice and precautions. To overcome pre-existing language barriers, participants advocated for the use of bilingual community educators, community radio, ethnic newspapers and posters in the dissemination of pre-travel health information. CONCLUSIONS: Travel is a major vector of importation of infectious diseases into Australia, and VFR travellers are at high risk of infection. Collaboration between the Government, primary care physicians, migrant community groups and migrants themselves is crucial if we are to be successful in reducing travel related risks among this subgroup of travellers. PMID- 27193515 TI - Functional and Taxonomic Diversity of Stinging Wasps in Brazilian Atlantic Rainforest Areas. AB - Vespoidea are the most functionally diverse superfamily of Hymenoptera. Ecological studies involving this family are primarily based on eusocial groups, including ants and social paper wasps. In the present study, we examine stinging wasp (Vespoidea) faunal diversity in the Atlantic Rain Forest, which is one of the most diverse and threatened ecosystems in the World. Three conservation areas were sampled employing a standardized sample protocol. Families and functional groups of Vespoidea were collected in each area, with the exception ants (Formicidae), and analyzed using diversity analyses, to generate taxonomic diversity and distinctness indices. Results indicated Pompilidae was the most diverse family, and the idiobiont parasitoid type was the most diverse functional group in the three study areas. Nucleo Picinguaba of the Parque Estadual da Serra do Mar was taxonomically and functionally the most diverse and species rich area. Parque Estadual Intervales showed the highest number of dominant species and diversity of koinobiont parasitoids, while the Rebio Sooretama exhibited a decrease in several diversity parameters. PMID- 27193517 TI - Workers' Extra-Nest Behavioral Changes During Colony Fission in Dinoponera quadriceps (Santschi). AB - Ant colonies can reproduce by two strategies: independent foundation, wherein the queen starts a new colony alone, and dependent foundation, in which workers assist the queen. In the queenless species Dinoponera quadriceps (Santschi), the colony reproduces obligatorily by fission, a type of dependent foundation, but this process is not well understood. This study describes a colony fission event of D. quadriceps in the field and analyzes the influence of the fission process on workers' extra-nest behavior. Based on observations of workers outside the nest, five distinct stages were identified: monodomic stage, polydomic stage, split stage, conflict stage, and post-conflict stage. The colony was initially monodomic and then occupied a second nest before it split into two independent colonies, indicating a gradual and opportunistic dependent foundation. After the fission event, the daughter colony had aggressive conflicts with the parental colony, resulting in the latter's disappearance. Colony fission affected workers' extra-nest behavior by increasing the frequency of rubbing the gaster against the substrate (which probably has a chemical marking function) and by decreasing the frequency of foraging during the split stage. After the fission event, the number of foragers was halved and foragers remained nearer to the nest during extra-nest activity. The spatial closeness of the parental and daughter colonies led to competition that caused the extinction or migration of the parental colony. Intraspecific competition was indicated by foraging directionality at the colony level, whereby areas of neighbor colonies were avoided; this directionality was stronger while both colonies coexisted. PMID- 27193516 TI - Identification and Expression Profile of Two Putative Odorant-Binding Proteins from the Neotropical Brown Stink Bug, Euschistus heros (Fabricius) (Hemiptera: Pentatomidae). AB - This work presents the first identification of putative odorant-binding proteins (OBPs) from a member of the Pentatomidae, i.e. the brown stink bug Euschistus heros (Fabricius), an important pest of soybean in Brazil. Antennae from both sexes of E. heros adults (12 days old and unmated) were used to construct a cDNA library, from which two transcripts encoding putative E. heros OBPs (EherOBPs) were identified. The expression levels of EherOBP1 and EherOBP2 were found to be higher in male antennae than in female and there was difference in expression in legs, wings, and abdomens of the two sexes. The histolocalization of EherOBP1 and EherOBP2 transcripts in antennae also showed a sexual dimorphism in the chemoreception system, with different expression sites in the antennal segments between males and females, occurring predominantly at the base of the sensillum. The implications of these findings for stink bug chemoreception are discussed. PMID- 27193518 TI - Blowflies (Diptera, Calliphoridae) Associated with Pig Carcasses in a Caatinga Area, Northeastern Brazil. AB - Studies that focused on Calliphoridae associated with pig carcasses are abundant in southern and southeastern Brazil; however, there are few in northeast. Here, we present an inventory of the blowfly species associated with the stages of decomposition of pig carcasses in a caatinga area during dry and rainy seasons. The study took place at the Private Reserve for the Environmental Inheritance "Fazenda Almas," state of Paraiba, Brazil. Using a modified version of the Shannon trap, 32,909 adult specimens belonging to eight species were captured. During the dry season, Cochliomyia macellaria (Fabricius) (52.2%) and Chrysomya albiceps (Wiedemann) (39.9%) were the most abundant species. In the rainy season, when the majority of individuals were captured (93.7%), Chloroprocta idioidea (Robineau-Desvoidy) (71.1%) was the most abundant. Five decomposition stages were recognized, being the active decay the most attractive to colonization by blowflies, except for Lucilia eximia (Wiedemann), which was more abundant in the bloated stage. PMID- 27193519 TI - Resource Utilization and Temporal Segregation of Scarabaeinae (Coleoptera, Scarabaeidae) Community in a Caatinga Fragment. AB - We characterized dung beetles food preference and diel activity and examined the way such characteristics may structure a Scarabaeinae community in a dry forest. We sampled a fragment of Arboreal Caatinga in Milagres, Bahia, Brazil, during the dry and wet seasons, using baited pitfall (bovine spleen, human feces, cow dung, and rotten banana). Species were classified by activity (nocturnal and diurnal) and food preference (coprophagous, necrophagous, saprophagous, copro necrophagous, and generalist). In total, 1,581 individuals belonging to 16 morphospecies were sampled, with six new records for Caatinga. The dung beetles were mainly from generalist and coprophagous species; seven species presented nocturnal activity, and five were diurnal. There was higher species richness during the day and greater abundance during the night. Species composition differences were influenced by functional guilds and beetle size according to temporal segregation. These factors may be related to physiological, morphological, and behavioral differences. PMID- 27193520 TI - The Usefulness of the Sting Apparatus in Phylogenetic Reconstructions in Vespids, with Emphasis on the Epiponini: More Support for the Single Origin of Eusociality in the Vespidae. AB - This study aimed at testing the utility of characters derived from chitinous structures of the sting apparatus for elucidating relationships among the genera of Epiponini. The characters were obtained from the spiracular and quadrate plates, gonostylus, and sting. The data matrix was analyzed using parsimony with equal and implied weighting. Sting characters were also optimized on the tree of Wenzel & Carpenter (1994). Consensus of analysis using equal weights parsimony resulted in a tree with low resolution, but the use of implied weighting improved the results and a consensus tree with a better resolution was obtained. Implied weighting analysis showed an interesting result with Vespinae and Epiponini (the taxa that present the highest degree of sociality) together in a clade. The overall uniformity in morphology of sting apparatus and a possible influence of sociality on morphology could explain these results. The evolution of some characters is discussed. PMID- 27193521 TI - A Review of the Copitarsia decolora (Guenee) (Lepidoptera: Noctuidae) Species Complex with the Description of a New Species from Chile and Argentina. AB - Copitarsia gibberosa n. sp. is described from Chile and Argentina. Morphological characters are discussed to differentiate it from Copitarsia decolora (Guenee), Copitarsia incommoda (Walker), and Copitarsia corruda (Pogue & Simmons). Copitarsia corruda has its status revised based on CO1 and morphology. Copitarsia paraturbata Castillo & Angulo is a new synonym of C. incommoda based on morphology. Copitarsia uncilata Burgos & Leiva is a new synonym of C. decolora based on morphology. A review of recent literature revealed a misunderstanding of the complex of species related to C. decolora, and these papers are evaluated and species are identified. Host plant utilization is discussed between C. decolora and C. corruda. Adults and male and female genitalia are illustrated to differentiate between the species in the C. decolora species complex. Keys to male and females based on genitalic morphology are given. Distribution maps of collected specimens are provided. PMID- 27193522 TI - Side Effects of Neem Oil on the Midgut Endocrine Cells of the Green Lacewing Ceraeochrysa claveri (Navas) (Neuroptera: Chrysopidae). AB - We described the ultrastructure of Ceraeochrysa claveri (Navas) midgut endocrine cells in larva, pupa, and adult, and evaluated the side effects of ingested neem oil, a botanical insecticide obtained from the seeds of the neem tree (Azadirachta indica), on these cells. During the larval period, C. claveri were fed (ad libitum) Diatraea saccharalis (F.) eggs treated with neem oil at concentrations of 0.5%, 1%, or 2%. Transmission electron microscopy showed that two subtypes of endocrine cells, namely granular and vesicular, occurred in the midgut epithelium during the three stages of the life cycle. Both cell types did not reach the midgut lumen and were positioned basally in the epithelium. The endocrine cells did not show extensive infoldings of the basal plasma membrane, and there were numerous secretory granules in the basal region of the cytoplasm. In the granular endocrine cells, the granules were completely filled with a dense matrix. In the vesicular endocrine cells, the main secretory products consisted of haloed vesicles. Ultrastructural examination indicated that only the granular endocrine cells exhibited signs of morphologic changes of cell injury present in all life cycle stages after the larvae were chronically exposed to neem oil by ingestion. The major cellular damage consisted of dilatation and vesiculation of the rough endoplasmic reticulum and the development of smooth endoplasmic reticulum and mitochondrial swelling. Our data suggest that cytotoxic effects on midgut endocrine cells can contribute to a generalized disruption of the physiological processes in this organ due to a general alteration of endocrine function. PMID- 27193523 TI - Further Ergatoid Gyne Records in the Ant Tribe Dacetini (Formicidae: Myrmicinae). AB - Variants of gynes and workers occur in a substantial number of ant species; however, dacetine ergatoid gynes have been recorded just once in the literature thus far. In the present paper, we provide abridged descriptions of five ergatoid female reproductives in five species of Neotropical dacetines belonging to two genera: Acanthognathus brevicornis Smith, Acanthognathus ocellatus Mayr, Acanthognathus rudis Brown & Kempf, Strumigenys cosmostela Kempf, and Strumigenys hindenburgi Forel. We also compare the ergatoids with conspecific gynes and workers. PMID- 27193524 TI - Allometry for Sexual Size Dimorphism in Stoneflies Defies the Rensch's Rule. AB - The Rensch's rule predicts that male-biased sexual size dimorphism (SSD) increases with body size, while female-biased SSD (FBSSD) decreases. In insects, many groups follow this rule, but the evidence suggests that it is taxon dependent and that the inverse of the rule can occur in species with FBSSD. Therefore, we conducted this study with Gripopterygidae stoneflies (Plecoptera) to describe their pattern of SSD and determine if they follow the Rensch's rule. Our data suggest that stoneflies exhibit FBSSD and do not follow the rule, but a reverse pattern. Our results corroborate other studies that suggest that the Rensch's rule is taxon based and that groups with FBSSD usually fail to obey the rule. PMID- 27193525 TI - Temperature-Dependent Parasitism, Survival, and Longevity of Five Species of Trichogramma Westwood (Hymenoptera: Trichogrammatidae) Associated with Anticarsia gemmatalis Hubner (Lepidoptera: Noctuidae). AB - Egg parasitoids of the genus Trichogramma Westwood play an important role in the control of the velvetbean caterpillar Anticarisa gemmatalis Hubner in soybean crops in Southern Brazil. The effectiveness of Trichogramma species as biocontrol agents is dependent of several factors, but their adaptation to the climatic conditions of the region where they will be released is one of the most important. In this context, this study evaluated the effects of five constant temperatures ranging from 14 to 30 degrees C on parasitism, age-specific survival, progeny production and longevity of Trichogramma pretiosum Riley, Trichogramma atopovirilia Oatman & Platner, Trichogramma acacioi Brun, Moraes & Soares, Trichogramma lasallei Pinto, and Trichogramma rojasi Nagaraja & Nagarkatti. We demonstrate that temperature differently affected the species of Trichogramma investigated when using eggs of the velvetbean caterpillar. We also demonstrate that T. pretiosum and T. atopovirilia are better adapted to a wide range of temperatures than the other species evaluated, and are therefore better suited as biocontrol agents for applied biological control programs of A. gemmatalis. PMID- 27193526 TI - Biology of the Two-Spotted Spider Mite on Strawberry Plants. AB - The two-spotted spider mite, Tetranychus urticae Koch, is commonly found on strawberry crops (Fragaria x ananassa). Strawberry plants have defensive mechanisms, which in turn influence the behavior of herbivores. The oviposition and development of the two-spotted spider mite were evaluated on the leaf disks of the cultivars 'Aromas,' 'Camarosa,' 'Camino Real,' 'Diamante,' 'Diamante 10,' 'Diamante 50,' 'Festival,' and 'Seascape.' It was observed that on cultivars such as 'Aromas,' 'Camarosa,' and 'Seascape,' immature survivorship was higher, but no difference was found during the developmental period from egg to adult of T. urticae. The immature development time was also longer on 'Camarosa.' Females laid more eggs on 'Seascape' (8.4 eggs/day), and the least on 'Camarosa' (1.0 egg/day). Mortality was higher at the larval stage and reached more than 50% in three cultivars 'Camarosa,' 'Diamante,' and 'Seascape.' Thus, the cultivars 'Camarosa,' 'Diamante,' and 'Seascape' were the ones that mostly affected the survival, development, and reproduction of T. urticae. PMID- 27193527 TI - Records of Natural Enemies of Bemisia tabaci (Genn.) (Hemiptera: Aleyrodidae) Biotype B in Brazil. AB - Collections of natural enemies of Bemisia tabaci biotype B (Genn.) (Hemiptera: Aleyrodidae) were made in Lavras, state of Minas Gerais, Brazil. In the greenhouse, 6,495 predators and 16,628 parasitoids belonging to three families were collected. In the field, 267 predators and 344 parasitoids belonging to five families were found. For the first time in Brazil, five species of predators associated with this whitefly were reported. Because of the diversity of natural enemies of B. tabaci biotype B recorded, this study points out the importance of these data for studies on integrated pest management. PMID- 27193528 TI - Atraumatic splenic rupture, an underrated cause of acute abdomen. PMID- 27193529 TI - Multidetector CT of expected findings and early postoperative complications after current techniques for ventral hernia repair. AB - Current techniques for ventral hernia repair (VHR) rely on prosthetic mesh implantation and are increasingly performed laparoscopically. Potentially serious iatrogenic complications may occur following VHR, though these are rare compared to the vast number of procedures performed each year. This paper provides an overview of contemporary open and laparoscopic surgical techniques and biomaterials, then reviews and illustrates the expected postoperative imaging appearances, and common and unusual early complications after VHR. Emphasis is placed on multidetector computed tomography (CT), which comprehensively visualizes the operated anterior abdominal wall and deeper intra-abdominal structures. CT consistently allows diagnosis of postoperative seromas, abdominal wall abscesses and fistulas, haemorrhages with or without active bleeding, bowel obstruction, peritonitis and recurrent hernias, and thus providing a reliable basis for an appropriate choice between conservative, interventional, or surgical treatment. Familiarity with early post-surgical CT is warranted to avoid misinterpretation of the expected imaging appearance and correctly elucidate postoperative complications after VHR. TEACHING POINTS: * Open and laparoscopic repair of ventral hernias rely on prosthetic mesh implantation. * Potentially serious iatrogenic complications occasionally occur after ventral hernioplasty. * Multidetector CT consistently evaluates the operated abdominal wall and deeper structures. * Familiarity with the expected early postoperative imaging appearance is required. * Complications include seroma, infections, haemorrhage, bowel obstruction, peritonitis, and recurrence. PMID- 27193530 TI - Effective techniques for changing physical activity and healthy eating intentions and behaviour: A systematic review and meta-analysis. AB - PURPOSE: The primary aim of this study was to review the evidence on the impact of a change in intention on behaviour and to identify (1) behaviour change techniques (BCTs) associated with changes in intention and (2) whether the same BCTs are also associated with changes in behaviour. METHODS: A systematic review was conducted to identify interventions that produced a significant change in intention and assessed the impact of this change on behaviour at a subsequent time point. Each intervention was coded using a taxonomy of BCTs targeting healthy eating and physical activity. A series of meta-regression analyses were conducted to identify effective BCTs. RESULTS: In total, 25 reports were included. Interventions had a medium-to-large effect on intentions (d+ = 0.64) and a small-to-medium effect (d+ = 0.41) on behaviour. One BCT, 'provide information on the consequences of behaviour in general', was significantly associated with a positive change in intention. One BCT, 'relapse prevention/coping planning', was associated with a negative change in intention. No BCTs were found to have significant positive effects on behaviour. However, one BCT, 'provide feedback on performance', was found to have a significant negative effect. BCTs aligned with social cognitive theory were found to have significantly greater positive effects on intention (d+ = 0.83 vs. 0.56, p < .05), but not behaviour (d+ = 0.35 vs. 0.23, ns), than those aligned with the theory of planned behaviour. CONCLUSIONS: Although the included studies support the notion that a change in intention is associated with a change in behaviour, this review failed to produce evidence on how to facilitate behaviour change through a change in intention. Larger meta-analyses incorporating interventions targeting a broader range of behaviours may be warranted. Statement of contribution What is already known on this subject? Prior research on the causal relationship between intention and behaviour has produced mixed findings. Further experimental research to determine the precise nature of these variables is clearly warranted. However, precise guidance on how to change intention is still lacking. What does this study add? This study aimed to identify behaviour change techniques associated with changes in intention and behaviour. Techniques with positive effects on intention were identified; however, these did not have an impact on behaviour. Larger meta-analyses incorporating interventions targeting a broader range of behaviours may be warranted. PMID- 27193531 TI - Competing covalent and ionic bonding in Ge-Sb-Te phase change materials. AB - Ge2Sb2Te5 and related phase change materials are highly unusual in that they can be readily transformed between amorphous and crystalline states using very fast melt, quench, anneal cycles, although the resulting states are extremely long lived at ambient temperature. These states have remarkably different physical properties including very different optical constants in the visible in strong contrast to common glass formers such as silicates or phosphates. This behavior has been described in terms of resonant bonding, but puzzles remain, particularly regarding different physical properties of crystalline and amorphous phases. Here we show that there is a strong competition between ionic and covalent bonding in cubic phase providing a link between the chemical basis of phase change memory property and origins of giant responses of piezoelectric materials (PbTiO3, BiFeO3). This has important consequences for dynamical behavior in particular leading to a simultaneous hardening of acoustic modes and softening of high frequency optic modes in crystalline phase relative to amorphous. This different bonding in amorphous and crystalline phases provides a direct explanation for different physical properties and understanding of the combination of long time stability and rapid switching and may be useful in finding new phase change compositions with superior properties. PMID- 27193533 TI - The Biophysics of Infection. AB - Our understanding of the processes involved in infection has grown enormously in the past decade due in part to emerging methods of biophysics. This new insight has been enabled through advances in interdisciplinary experimental technologies and theoretical methods at the cutting-edge interface of the life and physical sciences. For example, this has involved several state-of-the-art biophysical tools used in conjunction with molecular and cell biology approaches, which enable investigation of infection in living cells. There are also new, emerging interfacial science tools which enable significant improvements to the resolution of quantitative measurements both in space and time. These include single molecule biophysics methods and super-resolution microscopy approaches. These new technological tools in particular have underpinned much new understanding of dynamic processes of infection at a molecular length scale. Also, there are many valuable advances made recently in theoretical approaches of biophysics which enable advances in predictive modelling to generate new understanding of infection. Here, I discuss these advances, and take stock on our knowledge of the biophysics of infection and discuss where future advances may lead. PMID- 27193532 TI - Hyponatremia in patients with systemic lupus erythematosus. AB - The aim of this study was to determine whether decreased serum sodium concentration could be associated with the disease activity in SLE. We retrospectively analyzed the data of the two independent cohorts of children and adults with SLE in two centers. Hyponatremia was associated with serum chloride (p = 0.004), albumin (p = 0.002) and SLE disease activity index (SLEDAI) (p = 0.026) in children with SLE. Serum sodium levels were correlated negatively with ESR (p =0.001) and positively with serum albumin levels (p < 0.0001) and C3 (p = 0.008) in children with SLE and those levels were correlated negatively with serum interleukin-6 levels (p = 0.003) in adults with SLE. Independent risk factors for the development of hyponatremia were the decreased serum C3 levels (OR 1.069, p = 0.031), the decreased serum chloride levels (OR 2.054, p = 0.006) and increased erythrocyte sedimentation rate (ESR) (OR 1.066, p = 0.03) in children with SLE and increased C-reactive protein (CRP) (OR 1.480, p = 0.023) in combined cohorts with SLE by multiple logistic regression analyses. Our study firstly showed that hyponatremia could reflect a disease activity and severe inflammation of SLE. PMID- 27193534 TI - Single-Molecule Observation of DNA Replication Repair Pathways in E. coli. AB - The method of action of many antibiotics is to interfere with DNA replication quinolones trap DNA gyrase and topoisomerase proteins onto DNA while metronidazole causes single- and double-stranded breaks in DNA. To understand how bacteria respond to these drugs, it is important to understand the repair processes utilised when DNA replication is blocked. We have used tandem lac operators inserted into the chromosome bound by fluorescently labelled lac repressors as a model protein block to replication in E. coli. We have used dual colour, alternating-laser, single-molecule narrowfield microscopy to quantify the amount of operator at the block and simultaneously image fluorescently labelled DNA polymerase. We anticipate use of this system as a quantitative platform to study replication stalling and repair proteins. PMID- 27193535 TI - Investigating the Swimming of Microbial Pathogens Using Digital Holography. AB - To understand much of the behaviour of microbial pathogens, it is necessary to image living cells, their interactions with each other and with host cells. Species such as Escherichia coli are difficult subjects to image: they are typically microscopic, colourless and transparent. Traditional cell visualisation techniques such as fluorescent tagging or phase-contrast microscopy give excellent information on cell behaviour in two dimensions, but no information about cells moving in three dimensions. We review the use of digital holographic microscopy for three-dimensional imaging at high speeds, and demonstrate its use for capturing the shape and swimming behaviour of three important model pathogens: E. coli, Plasmodium spp. and Leishmania spp. PMID- 27193536 TI - What Is the 'Minimum Inhibitory Concentration' (MIC) of Pexiganan Acting on Escherichia coli?-A Cautionary Case Study. AB - We measured the minimum inhibitory concentration (MIC) of the antimicrobial peptide pexiganan acting on Escherichia coli , and found an intrinsic variability in such measurements. These results led to a detailed study of the effect of pexiganan on the growth curve of E. coli, using a plate reader and manual plating (i.e. time-kill curves). The measured growth curves, together with single-cell observations and peptide depletion assays, suggested that addition of a sub-MIC concentration of pexiganan to a population of this bacterium killed a fraction of the cells, reducing peptide activity during the process, while leaving the remaining cells unaffected. This pharmacodynamic hypothesis suggests a considerable inoculum effect, which we quantified. Our results cast doubt on the use of the MIC as 'a measure of the concentration needed for peptide action' and show how 'coarse-grained' studies at the population level give vital information for the correct planning and interpretation of MIC measurements. PMID- 27193537 TI - Evolution of Drug Resistance in Bacteria. AB - Resistance to antibiotics is an important and timely problem of contemporary medicine. Rapid evolution of resistant bacteria calls for new preventive measures to slow down this process, and a longer-term progress cannot be achieved without a good understanding of the mechanisms through which drug resistance is acquired and spreads in microbial populations. Here, we discuss recent experimental and theoretical advances in our knowledge how the dynamics of microbial populations affects the evolution of antibiotic resistance . We focus on the role of spatial and temporal drug gradients and show that in certain situations bacteria can evolve de novo resistance within hours. We identify factors that lead to such rapid onset of resistance and discuss their relevance for bacterial infections. PMID- 27193538 TI - Using Biophysics to Monitor the Essential Protonmotive Force in Bacteria. AB - Protonmotive force is an essential biological energy format in all levels of cells. Protonmotive force comprises electrical and chemical potential difference across biological membrane. In bacteria, protonmotive force couples to metabolism and ATP production. Moreover, protonmotive force directly provides driving energy of bacterial flagellar motor that is critical for bacterial motility and infection. Due to the small size of bacterial cells, there were limited experimental tools to measure protonmotive force in bacteria. Recent developments of optical membrane potential and intracellular pH indicators provide valuable information on bacterial studies. These new biophysical techniques allow us to monitor the protonmotive force even in single bacterial cell level that shed the light of next generation single-cell physiological experiments towards the understanding of bacterial infection process. PMID- 27193539 TI - The Type I Restriction Enzymes as Barriers to Horizontal Gene Transfer: Determination of the DNA Target Sequences Recognised by Livestock-Associated Methicillin-Resistant Staphylococcus aureus Clonal Complexes 133/ST771 and 398. AB - The Type I DNA restriction-modification (RM) systems of Staphylococcus aureus are known to act as a significant barrier to horizontal gene transfer between S. aureus strains belonging to different clonal complexes. The livestock-associated clonal complexes CC133/771 and CC398 contain Type I RM systems not found in human MRSA strains as yet but at some point transfer will occur. When this does take place, horizontal gene transfer of resistance will happen more easily between these strains. The reservoir of antibiotic resistance, virulence and host adaptation genes present in livestock-associated MRSA will then potentially contribute to the development of newly evolving MRSA clones. The target sites recognised by the Type I RM systems of CC133/771 and CC398 were identified as CAG(N)5RTGA and ACC(N)5RTGA, respectively. Assuming that these enzymes recognise the methylation state of adenine, the underlined A and T bases indicate the unique positions of methylation. Target methylation points for enzymes from CC1 were also identified. The methylation points for CC1-1 are CCAY(N)5TTAA and those for CC1-2 are CCAY(N)6 TGT with the underline indicating the adenine methylation site thus clearing up the ambiguity noted previously (Roberts et al. 2013, Nucleic Acids Res 41:7472-7484) for the half sites containing two adenine bases. PMID- 27193540 TI - Biomechanical Analysis of Infectious Biofilms. AB - The removal of infectious biofilms from tissues or implanted devices and their transmission through fluid transport systems depends in part of the mechanical properties of their polymeric matrix. Linking the various physical and chemical microscopic interactions to macroscopic deformation and failure modes promises to unveil design principles for novel therapeutic strategies targeting biofilm eradication, and provide a predictive capability to accelerate the development of devices, water lines, etc, that minimise microbial dispersal. Here, our current understanding of biofilm mechanics is appraised from the perspective of biophysics , with an emphasis on constitutive modelling that has been highly successful in soft matter. Fitting rheometric data to viscoelastic models has quantified linear and nonlinear stress relaxation mechanisms, how they vary between species and environments, and how candidate chemical treatments alter the mechanical response. The rich interplay between growth, mechanics and hydrodynamics is just becoming amenable to computational modelling and promises to provide unprecedented characterisation of infectious biofilms in their native state. PMID- 27193541 TI - Designing a Single-Molecule Biophysics Tool for Characterising DNA Damage for Techniques that Kill Infectious Pathogens Through DNA Damage Effects. AB - Antibiotics such as the quinolones and fluoroquinolones kill bacterial pathogens ultimately through DNA damage. They target the essential type IIA topoisomerases in bacteria by stabilising the normally transient double-strand break state which is created to modify the supercoiling state of the DNA. Here we discuss the development of these antibiotics and their method of action. Existing methods for DNA damage visualisation, such as the comet assay and immunofluorescence imaging can often only be analysed qualitatively and this analysis is subjective. We describe a putative single-molecule fluorescence technique for quantifying DNA damage via the total fluorescence intensity of a DNA origami tile fully saturated with an intercalating dye, along with the optical requirements for how to implement these into a light microscopy imaging system capable of single-molecule millisecond timescale imaging. This system promises significant improvements in reproducibility of the quantification of DNA damage over traditional techniques. PMID- 27193542 TI - Bacterial Surfaces: Front Lines in Host-Pathogen Interaction. AB - All bacteria are bound by at least one membrane that acts as a barrier between the cell's interior and the outside environment. Surface components within and attached to the cell membrane are essential for ensuring that the overall homeostasis of the cell is maintained. However, many surface components of the bacterial cell also have an indispensable role mediating interactions of the bacteria with their immediate environment and as such are essential to the pathogenesis of infectious disease. During the course of an infection, bacterial pathogens will encounter many different ecological niches where environmental conditions such as salinity, temperature, pH, and the availability of nutrients fluctuate. It is the bacterial cell surface that is at the front-line of these host-pathogen interactions often protecting the bacterium from hostile surroundings but at the same time playing a critical role in the adherence to host tissues promoting colonization and subsequent infection. To deal effectively with the changing environments that pathogens may encounter in different ecological niches within the host many of the surface components of the bacterial cell are subject to phenotypic variation resulting in heterogeneous subpopulations of bacteria within the clonal population. This dynamic phenotypic heterogeneity ensures that at least a small fraction of the population will be adapted for a particular circumstance should it arise. Diversity within the clonal population has often been masked by studies on entire bacterial populations where it was often assumed genes were expressed in a uniform manner. This chapter, therefore, aims to highlight the non-uniformity in certain cell surface structures and will discuss the implication of this heterogeneity in bacterial-host interaction. Some of the recent advances in studying bacterial surface structures at the single cell level will also be reviewed. PMID- 27193543 TI - Biophysical Approaches to Bacterial Gene Regulation by Riboswitches. AB - The last decade has witnessed the discovery of a variety of non-coding RNA sequences that perform a broad range of crucial biological functions. Among these, the ability of certain RNA sequences, so-called riboswitches, has attracted considerable interest. Riboswitches control gene expression in response to the concentration of particular metabolites to which they bind without the need for any protein. These RNA switches not only need to adopt a very specific tridimensional structure to perform their function, but also their sequence has been evolutionary optimized to recognize a particular metabolite with high affinity and selectivity. Thus, riboswitches offer a unique opportunity to get fundamental insights into RNA plasticity and how folding dynamics and ligand recognition mechanisms have been efficiently merged to control gene regulation. Because riboswitch sequences have been mostly found in bacterial organisms controlling the expression of genes associated to the synthesis, degradation or transport of crucial metabolites for bacterial survival, they offer exciting new routes for antibiotic development in an era where bacterial resistance is more than ever challenging conventional drug discovery strategies. Here, we give an overview of the architecture, diversity and regulatory mechanisms employed by riboswitches with particular emphasis on the biophysical methods currently available to characterise their structure and functional dynamics. PMID- 27193544 TI - Bugs on a Slippery Plane : Understanding the Motility of Microbial Pathogens with Mathematical Modelling. AB - Many pathogenic microorganisms live in close association with surfaces, typically in thin films that either arise naturally or that they themselves create. In response to this constrained environment, the cells adjust their behaviour and morphology, invoking communication channels and inducing physical phenomena that allow for rapid colonization of biomedically relevant surfaces or the promotion of virulence factors. Thus, it is very important to measure and theoretically understand the key mechanisms for the apparent advantage obtained from swimming in thin films. We discuss experimental measurements of flows around a peritrichously flagellated bacterium constrained in a thin film, derive a simplified mathematical theory and Green's functions for flows in a thin film with general slip boundary conditions, and establish connections between theoretical and experimental results. This article aims to highlight the importance of mathematics as a tool to unlock qualitative mechanisms associated with experimental observations in the medical and biological sciences. PMID- 27193546 TI - How Biophysics May Help Us Understand the Flagellar Motor of Bacteria Which Cause Infections. AB - Motor proteins are molecules which convert chemical energy to mechanical work and are responsible for motility across all levels: for transport within a cell, for the motion of an individual cell in its surroundings, and for movement in multicellular aggregates, such as muscles. The bacterial flagellar motor is one of the canonical examples of a molecular complex made from several motor proteins, which self-assembles on demand and provides the locomotive force for bacteria. This locomotion provides a key aspect of bacteria's prevalence. Here, we outline the biophysics behind the assembly, the energetics, the switching and the rotation of this remarkable nanoscale electric motor that is Nature's first wheel. PMID- 27193545 TI - Transcription Regulation and Membrane Stress Management in Enterobacterial Pathogens. AB - Transcription regulation in a temporal and conditional manner underpins the lifecycle of enterobacterial pathogens. Upon exposure to a wide array of environmental cues, these pathogens modulate their gene expression via the RNA polymerase and associated sigma factors. Different sigma factors, either involved in general 'house-keeping' or specific responses, guide the RNA polymerase to their cognate promoter DNAs. The major alternative sigma54 factor when activated helps pathogens manage stresses and proliferate in their ecological niches. In this chapter, we review the function and regulation of the sigma54-dependent Phage shock protein (Psp) system-a major stress response when Gram-negative pathogens encounter damages to their inner membranes. We discuss the recent development on mechanisms of gene regulation, signal transduction and stress mitigation in light of different biophysical and biochemical approaches. PMID- 27193547 TI - Mechanics of Bacterial Cells and Initial Surface Colonisation. AB - The mechanical properties of bacterial cells play an important role in crucial bacterial processes such as cell growth, colonisation and biofilm formation. Recent developments in the field of nanotechnology and atomic force microscopy (AFM) have made it possible to observe, characterise and understand the nanomechanic behaviour of live bacterial cells as never before. Unlike traditional techniques, AFM makes it possible to employ living bacteria in their physiological environment with minimal or no sample preparation. The technique of AFM nanoindentation opens new possibilities to study bacterial cell wall stiffness under different mechanical and buffer conditions. Also, by attaching bacterial cells to functionalised AFM cantilevers, single-cell force spectroscopy (SCFS) can be used to measure the adhesion of bacteria to biological and non biological substrates at the nano-newton and pico-newton scale, and provide specific information on receptor-ligand interactions. By studying the biophysics of the bacterial-surface interaction with the abovementioned techniques, it has been possible to gain new insight on the early stages of bacterial colonisation and biofilm formation. PMID- 27193548 TI - Neutron Reflectivity as a Tool for Physics-Based Studies of Model Bacterial Membranes. AB - The principles of neutron reflectivity and its application as a tool to provide structural information at the (sub-) molecular unit length scale from models for bacterial membranes are described. The model membranes can take the form of a monolayer for a single leaflet spread at the air/water interface, or bilayers of increasing complexity at the solid/liquid interface. Solid-supported bilayers constrain the bilayer to 2D but can be used to characterize interactions with antimicrobial peptides and benchmark high throughput lab-based techniques. Floating bilayers allow for membrane fluctuations, making the phase behaviour more representative of native membranes. Bilayers of varying levels of compositional accuracy can now be constructed, facilitating studies with aims that range from characterizing the fundamental physical interactions, through to the characterization of accurate mimetics for the inner and outer membranes of Gram-negative bacteria. Studies of the interactions of antimicrobial peptides with monolayer and bilayer models for the inner and outer membranes have revealed information about the molecular control of the outer membrane permeability, and the mode of interaction of antimicrobials with both inner and outer membranes. PMID- 27193549 TI - Mechanisms of Salmonella Typhi Host Restriction. AB - Salmonella enterica serovar Typhi (S. Typhi) is the cause of typhoid fever, a life-threatening bacterial infection that is very common in the developing world. Recent spread of antimicrobial resistant isolates of S. Typhi makes typhoid fever, a global public health risk. Despite being a common disease, still very little is known about the molecular mechanisms underlying typhoid fever and S. Typhi pathogenesis. In contrast to other Salmonellae, S. Typhi can only infect humans. The molecular bases of this human restriction are mostly unknown. Recent studies identified a novel pathway that contributes to S. Typhi human restriction and is required for killing S. Typhi in macrophages of nonsusceptible species. The small Rab GTPase Rab32 and its guanine nucleotide exchange factor BLOC-3 are the critical components of this pathway. These proteins were already well known as important regulators of intracellular membrane transport. In particular, they are central for the transport of enzymes that synthetize melanin in pigment cells. The recent findings that Rab32 and BLOC-3 are required for S. Typhi host restriction point out to a novel mechanism restricting the growth of bacterial pathogen, dependent on the transport of still unknown molecule(s) to the S. Typhi vacuole. The identification of this novel antimicrobial pathway constitutes a critical starting point to study molecular mechanisms killing bacterial pathogens and possibly identify novel antimicrobial molecules. PMID- 27193550 TI - Insights into Biological Complexity from Simple Foundations. AB - We discuss an overtly "simple approach" to complex biological systems borrowing selectively from theoretical physics. The approach is framed by three maxims, and we show examples of its success in two different applications: investigating cellular robustness at the level of gene regulatory networks and quantifying rare events of DNA replication errors. PMID- 27193551 TI - Force Spectroscopy in Studying Infection. AB - Biophysical force spectroscopy tools-for example, optical tweezers, magnetic tweezers, atomic force microscopy-have been used to study elastic, mechanical, conformational and dynamic properties of single biological specimens from single proteins to whole cells to reveal information not accessible by ensemble average methods such as X-ray crystallography, mass spectroscopy, gel electrophoresis and so on. Here, we review the application of these tools on a range of infection related questions from antibody-inhibited protein processivity to virus-cell adhesion. In each case, we focus on how the instrumental design tailored to the biological system in question translates into the functionality suitable for that particular study. The unique insights that force spectroscopy has gained to complement knowledge learned through population averaging techniques in interrogating biomolecular details prove to be instrumental in therapeutic innovations such as those in structure-based drug design. PMID- 27193552 TI - Imaging Immunity in Lymph Nodes: Past, Present and Future. AB - Immune responses occur as a result of stochastic interactions between a plethora of different cell types and molecules that regulate the migration and function of innate and adaptive immune cells to drive protection from pathogen infection. The trafficking of immune cells into peripheral tissues during inflammation and then subsequent migration to draining lymphoid tissues has been quantitated using radiolabelled immune cells over 40 years ago. However, how these processes lead to efficient immune responses was unclear. Advances in physics (multi-photon), chemistry (probes) and biology (animal models) have provided immunologists with specialized tools to quantify the molecular and cellular mechanisms driving immune function in lymphoid tissues through directly visualising cellular behaviours in 3-dimensions over time. Through the temporal and spatial resolution of multi-photon confocal microscopy immunologists have developed new insights into normal immune homeostasis, host responses to pathogens, anti-tumour immune responses and processes driving development of autoimmune pathologies, by the quantification of the interactions and cellular migration involved in adaptive immune responses. Advances in deep tissue imaging, including new fluorescent proteins, increased resolution, speed of image acquisition, sensitivity, number of signals and improved data analysis techniques have provided unprecedented capacity to quantify immune responses at the single cell level. This quantitative information has facilitated development of high-fidelity mathematical and computational models of immune function. Together this approach is providing new mechanistic understanding of immune responses and new insights into how immune modulators work. Advances in biophysics have therefore revolutionised our understanding of immune function, directly impacting on the development of next generation immunotherapies and vaccines, and is providing the quantitative basis for emerging technology of simulation-guided experimentation and immunotherapeutic design. PMID- 27193553 TI - Novel Approaches to Manipulating Bacterial Pathogen Biofilms: Whole-Systems Design Philosophy and Steering Microbial Evolution. AB - Understanding and manipulating bacterial biofilms is crucial in medicine, ecology and agriculture and has potential applications in bioproduction, bioremediation and bioenergy. Biofilms often resist standard therapies and the need to develop new means of intervention provides an opportunity to fundamentally rethink our strategies. Conventional approaches to working with biological systems are, for the most part, "brute force", attempting to effect control in an input and effort intensive manner and are often insufficient when dealing with the inherent non linearity and complexity of living systems. Biological systems, by their very nature, are dynamic, adaptive and resilient and require management tools that interact with dynamic processes rather than inert artefacts. I present an overview of a novel engineering philosophy which aims to exploit rather than fight those properties, and hence provide a more efficient and robust alternative. Based on a combination of evolutionary theory and whole-systems design, its essence is what I will call systems aikido; the basic principle of aikido being to interact with the momentum of an attacker and redirect it with minimal energy expenditure, using the opponent's energy rather than one's own. In more conventional terms, this translates to a philosophy of equilibrium engineering, manipulating systems' own self-organisation and evolution so that the evolutionarily or dynamically stable state corresponds to a function which we require. I illustrate these ideas with a description of a proposed manipulation of environmental conditions to alter the stability of co-operation in the context of Pseudomonas aeruginosa biofilm infection of the cystic fibrosis lung. PMID- 27193556 TI - Computational Systems Biomedicine. PMID- 27193554 TI - Prognostic factors in recurrent glioblastoma patients treated with bevacizumab. AB - The value of bevacizumab (BEV) in recurrent glioblastoma is unclear. Imaging parameters and progression-free survival (PFS) are problematic endpoints. Few data exist on clinical factors influencing overall survival (OS) in unselected patients with recurrent glioblastoma exposed to BEV. We retrospectively analyzed 174 patients with recurrent glioblastoma treated with BEV at two German brain tumor centers. We evaluated general patient characteristics, MGMT status, pretreatment, concomitant oncologic treatment and overall survival. Karnofsky performance score, number of prior chemotherapies, number of prior recurrences and combined treatment with irinotecan (IRI) were significantly associated with OS in univariate analysis. We did not find differences in OS related to sex, age, histology, MGMT status, prior surgical treatment or number of prior radiotherapies. Combined treatment with IRI and higher KPS both remained significantly associated with prolonged survival in multivariate analysis, but patients receiving IRI co-treatment had less advanced disease. Grouping into clinically relevant categories revealed an OS of 16.9 months from start of BEV in patients with first recurrence and KPS >= 80 % (n = 25). In contrast, in patients with second recurrence and KPS < 80 %, OS was 3.6 months (n = 27). Our observational data support an early use of BEV in patients with good performance status. The benefit of co-treatment with IRI in our cohort seems to be the result of biased patient recruitment. PMID- 27193555 TI - Transforming growth factor-beta and stem cell markers are highly expressed around necrotic areas in glioblastoma. AB - Invasion into surrounding normal brain and resistance to genotoxic therapies are the main devastating aspects of glioblastoma (GBM). These biological features may be associated with the stem cell phenotype, which can be induced through a dedifferentiation process known as epithelial-mesenchymal transition (EMT). We show here that tumor cells around pseudopalisading necrotic areas in human GBM tissues highly express the most important EMT inducer, transforming growth factor (TGF-beta), concurrently with the EMT-related transcriptional factor, TWIST. In addition, the stem cell markers CD133 and alkaline phosphatase (ALPL) were also highly expressed around necrotic foci in GBM tissues. The high expression of TGF beta around necrotic regions was significantly correlated with shorter progression-free survival and overall survival in patients with GBM. High expression of stem cell markers, ALPL, CD133, and CD44 was also correlated with poor outcomes. These results collectively support the hypothesis that tissue hypoxia induces the stem cell phenotype through TGF-beta-related EMT and contributes to the poor outcome of GBM patients. PMID- 27193557 TI - The validity and reliability of a signal impact assessment tool. AB - BACKGROUND: The Netherlands Pharmacovigilance Centre Lareb uses an operating Signal Impact Assessment Tool (SIAT) as aid in signal selection. SIAT prioritized signals into one of four categories: strong/moderate signal strength and similarly health impact. Although the SIAT has been used for many years, validity and reliability was never explored. PURPOSE: The aim of this study is to test the validity and reliability of the operating and weight-adjusted SIAT. METHOD: For validity testing, judgments of a Delphi panel of three pharmacovigilance experts were used as a 'gold standard'. First, the panel judged the weighting of the items included in the SIAT. Then, during two phases, the panel rated 40 signals in one of the four categories. Two researchers scored the signals using the SIAT. Panel judgments were compared with scores for the operating and weight-adjusted SIAT. Inter- and intra-observer variability was also tested. The Cohen's Kappa coefficient (k) was calculated. At least substantial agreement (k > 0.6) was considered to be necessary for an acceptable reliability. RESULTS: Validity did not meet predefined criteria: operating and weight-adjusted tool, respectively, k phase1 = 0.83 and 0.83, k-phase2 = 0.18 and 0.36. Differences were found for signal strength and health impact. Inter- and intra-observer variabilities were good, k of 0.78 and 0.72, respectively. CONCLUSIONS: The SIAT was found to have an insufficient validity and proper reliability. Although SIAT scores should not be decisive in the decision making process, items included can be used as an aid to decide which signals deserve further investigation. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27193559 TI - Sebacinales - one thousand and one interactions with land plants. AB - 20 I 21 II 21 III 23 IV 29 V 33 VI 35 36 36 References 36 SUMMARY: Root endophytism and mycorrhizal associations are complex derived traits in fungi that shape plant physiology. Sebacinales (Agaricomycetes, Basidiomycota) display highly diverse interactions with plants. Although early-diverging Sebacinales lineages are root endophytes and/or have saprotrophic abilities, several more derived clades harbour obligate biotrophs forming mycorrhizal associations. Sebacinales thus display transitions from saprotrophy to endophytism and to mycorrhizal nutrition within one fungal order. This review discusses the genomic traits possibly associated with these transitions. We also show how molecular ecology revealed the hyperdiversity of Sebacinales and their evolutionary diversification into two sister families: Sebacinaceae encompasses mainly ectomycorrhizal and early-diverging saprotrophic species; the second family includes endophytes and lineages that repeatedly evolved ericoid, orchid and ectomycorrhizal abilities. We propose the name Serendipitaceae for this family and, within it, we transfer to the genus Serendipita the endophytic cultivable species Piriformospora indica and P. williamsii. Such cultivable Serendipitaceae species provide excellent models for root endophytism, especially because of available genomes, genetic tractability, and broad host plant range including important crop plants and the model plant Arabidopsis thaliana. We review insights gained with endophytic Serendipitaceae species into the molecular mechanisms of endophytism and of beneficial effects on host plants, including enhanced resistance to abiotic and pathogen stress. PMID- 27193558 TI - Therapeutic surfactant-stripped frozen micelles. AB - Injectable hydrophobic drugs are typically dissolved in surfactants and non aqueous solvents which can induce negative side-effects. Alternatives like 'top down' fine milling of excipient-free injectable drug suspensions are not yet clinically viable and 'bottom-up' self-assembled delivery systems usually substitute one solubilizing excipient for another, bringing new issues to consider. Here, we show that Pluronic (Poloxamer) block copolymers are amenable to low-temperature processing to strip away all free and loosely bound surfactant, leaving behind concentrated, kinetically frozen drug micelles containing minimal solubilizing excipient. This approach was validated for phylloquinone, cyclosporine, testosterone undecanoate, cabazitaxel and seven other bioactive molecules, achieving sizes between 45 and 160 nm and drug to solubilizer molar ratios 2-3 orders of magnitude higher than current formulations. Hypertonic saline or co-loaded cargo was found to prevent aggregation in some cases. Use of surfactant-stripped micelles avoided potential risks associated with other injectable formulations. Mechanistic insights are elucidated and therapeutic dose responses are demonstrated. PMID- 27193560 TI - Rewards of Persistence: Manometric Clues to Cancer. PMID- 27193561 TI - Endoscopic Features and Eosinophil Density Are Associated with Food Impaction in Adults with Esophageal Eosinophilia. AB - BACKGROUND AND AIMS: Food impaction has been described in both eosinophilic esophagitis and proton pump inhibitor-responsive esophageal eosinophilia. The association between endoscopic/histologic features of esophageal eosinophilia and food impaction remains unclear. We aimed to identify clinical, endoscopic, and histologic findings associated with a history of food impaction in esophageal eosinophilia. METHODS: This was a retrospective cohort study of adult esophageal eosinophilia patients at a tertiary center in 6/2005-10/2014. Only patients with >=15 eosinophils/high-power field on mucosal biopsies were included. Demographics, comorbidities, symptoms, endoscopic/histologic findings on initial endoscopy, and history of food impaction were reviewed. Statistical analyses were performed using Fisher's exact test (univariate) and forward stepwise logistic regression (multivariate). RESULTS: 400 patients (42 +/- 14 years, 61 % male) were included, with 78 (20 %) having food impaction history. On univariate analyses, rings (62 vs 42 %, p = 0.003), erosions (12 vs 5 %, p = 0.03), eosinophil density on biopsy (40 [IQR = 30-50] vs 30 [IQR = 15-50], p = 0.004), and dysphagia (88 vs 62 %, p < 0.0001) were more prevalent among patients with food impaction history, while heartburn (10 vs 33 %, p < 0.0001) and abdominal pain (1 vs 12 %, p = 0.002) were less common. On multivariate analysis, rings (OR 2.6, p = 0.002), erosions (OR 3.2, p = 0.02), and eosinophil density (beta coefficient = 0.01, p = 0.04) remained associated with food impaction. CONCLUSIONS: Findings of rings and erosions on endoscopy and increased eosinophil density on histology were independently associated with a history of food impaction in adult esophageal eosinophilia patients. Food impaction may result from both active inflammation (erosions and increased eosinophil density) and chronic fibrostenotic changes (rings). PMID- 27193562 TI - Endoscopic Gastric Food Retention in Relation to Scintigraphic Gastric Emptying Delays and Clinical Factors. AB - BACKGROUND: Gastric food residue frequently is observed on endoscopy despite fasting. AIMS: To delineate factors promoting endoscopic food retention in the stomach. METHODS: Two series of analyses were performed. Magnitudes of retained food in 834 patients from an endoscopy database were related to obstructive versus non-obstructive etiologies and gastric emptying findings. Emptying delays in 619 patients from a scintigraphy database were associated with endoscopic food retention, gastroparesis etiologies, and medications that modify gastric transit. RESULTS: On endoscopy, 310 (37 %) had large, 338 (41 %) showed medium, and 103 (12 %) exhibited small amounts of retained food in the stomach. Of 433 patients with definable etiologies of food retention, 106 (24 %) had obstructive causes. One hundred three of 327 (31 %) with non-obstructive conditions underwent scintigraphy showing mean 52 +/- 29 % 4-h retention. From the scintigraphy database, 164/619 patients (26 %) with delayed emptying exhibited food retention on endoscopy. Four-hour scintigraphic retention was greater with versus without retained food (41 +/- 25 vs. 32 +/- 22 %, P < 0.001). Retained food occurred more frequently with postsurgical (28/69, 41 %) versus diabetic (33/139, 24 %) and idiopathic (65/294, 22 %) gastroparesis (P = 0.006). Opiate use was more prevalent with increasing food retention (P = 0.02), while other medications that delay or accelerate emptying did not relate to retained food. CONCLUSIONS: Gastric food retention has obstructive and non-obstructive causes, and is found in one-quarter of gastroparesis, especially postsurgical cases. Gastric emptying delays correlate with amounts of retained food on endoscopy. Retention is influenced by opiates, but not other medications. These analyses delineate pathogenic factors promoting gastric food retention. PMID- 27193565 TI - Pursuing a Clinical Academic Career During Gastroenterology Fellowship. PMID- 27193564 TI - Extra-Gastrointestinal Manifestations of Inflammatory Bowel Disease May Be Less Common Than Previously Reported. AB - BACKGROUND AND AIMS: Extra-intestinal manifestations are well recognized in inflammatory bowel disease (IBD). To what extent the commonly recognized extra intestinal manifestations seen in IBD patients are attributable to IBD is, however, not clear due to the limited number of controlled studies published. METHODS: We have conducted a study of these manifestations using electronic primary care records. We have identified extra-intestinal manifestations in IBD and non-IBD patients and derived odds ratios (ORs) using conditional logistic regression. RESULTS: A total of 56,097 IBD patients (32.5 % Crohn's disease, 48.3 % ulcerative colitis (UC) and 19.2 % not classified) were matched to 280,382 non IBD controls. We found records of pyoderma gangrenosum (OR = 29.24), erythema nodosum (OR = 5.95), primary sclerosing cholangitis (OR = 188.25), uveitis (OR = 2.81), ankylosing spondylitis (OR = 7.07), sacroiliitis (OR = 2.79) and non rheumatoid inflammatory arthritides (OR = 2.66) to be associated with IBD. One or more of these was recorded in 8.1 % of IBD patients and 2.3 % of controls. Non specific arthritides were present in many more patients, affecting 30 % of IBD patients and 23.8 % of controls overall. We also found weaker associations with a number of conditions not generally considered to be extra-intestinal manifestations including psoriasis, ischemic heart disease, multiple sclerosis and hay fever. CONCLUSION: Although "classical" extra-intestinal manifestations are strongly associated with IBD, most IBD patients remain unaffected. Arthropathies, perceived to be the commonest extra-intestinal manifestation, are not strongly associated with IBD, and the proportion of arthropathies attributable to IBD is likely to be small. PMID- 27193563 TI - Weight Change and Obesity Are Associated with a Risk of Adenoma Recurrence. AB - BACKGROUND: Obesity is reportedly a risk factor for colorectal adenoma. However, the influence of weight change and obesity on colorectal adenoma recurrence is unclear. AIM: To investigate whether weight change and obesity are associated with recurrence and development of colorectal adenoma. PATIENTS AND METHODS: Of 62,171 asymptomatic subjects who underwent a colonoscopy for a heath checkup between 2010 and 2011, this longitudinal study was performed with the 5297 subjects who underwent another colonoscopy between 2012 and 2013. The risk of recurrence or development of adenoma according to quartiles of weight change (< 1.6, -1.6 to 0.1, 0.2-1.8, and >=1.9 kg) and baseline BMI categories (<25, 25-29, and >=30 kg/m(2)) was assessed using Cox proportional hazards modeling. RESULTS: The average period between visits 1 and 2 was 2.2 +/- 0.6 years. Among the 2176 subjects with adenomas, the risk of recurrence of any adenoma increased with increasing weight change quartiles (p for trend = 0.030), whereas the risk of recurrence of advanced adenoma was not associated with weight change (p for trend = 0.852). The risk of recurrence of advanced adenoma increased with increasing baseline BMI categories (p for trend = 0.029). Among 3121 subjects with no adenoma, the risk of developing any adenoma increased with increasing baseline BMI categories (p for trend <0.001). However, the risk of developing any or advanced adenoma was not associated with weight change. CONCLUSIONS: Weight change over 2.2 years affected adenoma recurrence and obesity was related to advanced adenoma recurrence and adenoma development. PMID- 27193566 TI - Which patient- and physician-related factors are associated with guideline adherent initiation of adjuvant endocrine therapy? Results of the prospective multi-centre cohort study BRENDA II. AB - BACKGROUND: We analysed factors that might influence patients' and physicians' decisions against the initiation of guideline adherent adjuvant endocrine therapy (ET). METHODS: In a prospective multi-centre study, including four certified breast cancer centres in Germany, patients with primary breast cancer were included from 2009 to 2012. Patients completed a questionnaire prior to surgery, adjuvant therapy, and 6 months after adjuvant therapy. This questionnaire assessed health-related quality of life (QoL), psychiatric co-morbidity, demographic characteristics, and the intensity of fear for ET. Guideline adherence was classified based on an algorithm derived from international guidelines. The tumour board's (TB) decisions against or for ET was documented. The TB was blinded regarding the guideline results. RESULTS: In 666 patients, adjuvant ET was indicated according to the guideline recommendations. The TB decided in 92.3 % (n = 615) of those that adjuvant ET was indicated. TB's decision against ET was associated with the younger age of patients (OR = 0.5; 95 % CI 0.3-0.9) and poor QoL (OR = 1.7; 95 % CI 1.0-2.8). In 93 patients, ET was not indicated according to the guidelines, and the TB decided in 84 of those not to prescribe ET. The TB decided in 93.4 % of the cases according to the guidelines. Of the patients, where the TB prescribed ET, 5 % (n = 31) decided against ET. This decision was associated with fear of ET (OR = 2.2; 95 % CI 1.0 5.2) and higher age (OR 9; 95 % CI 1.0-48.1). Psychiatric co-morbidity (OR = 1.8; 95 % CI 0.7-4.2), poor QoL (OR = 0.4; 95 % CI 0.2-1.2), and education (OR = 1.2; 95 % CI 0.5-2.6) were not associated with the decision. DISCUSSION: Guideline adherent implementation of adjuvant ET is high. Physicians' decision against ET is mainly associated with patients' younger age and poor quality of life, whereas patients' decision, once the TB decided to initiate ET and if ET is indicated by guidelines, is associated with higher age and fear of ET. PMID- 27193568 TI - Development and Assessment of a Gas Chromatographic Based Method for the Quantification of Thymol from Cream Based Formulation. AB - INTRODUCTION: Herbal medicines have been used for different illnesses. However, standardization of these medicaments should be done before introducing for treatment purposes. Ajwain an essential oil, is traditionally used for neuropathic pain. OBJECTIVE: To develop and assess a gas chromatographic-based method for the quantification of thymol in Ajwain essential oil, current work was performed. METHODOLOGY: Both pure thymol and Ajwain creams were prepared and subjected to hydrodistillation method under temperature-controlled procedure to re-extract the applied essential oil and pure thymol. Previously, Ajwain seeds essential oil composition was analyzed and identified using GC/MS. After re extraction, GC/FID was applied quantitatively to determine the thymol content in the Ajwain and thymol creams. The parameters represented in International Conference on Harmonization (ICH) guidelines were considered for the determination. RESULTS: Thymol content in a 50 g laminated tube of Ajwain cream was calculated as 2.34 g +/- 0.02. Regarding the total thymol content of a 50 g laminated tube of Thymol cream (2.43 g), recovery percent for Ajwain cream was calculated as 96.29 %. CONCLUSION: Using hydrodistillation for an essential oil- containing cream sample via Clevenger proved to be a simple and convenient method to work up and extract active volatile components of such semisolid formulation. However, the extraction yield was profoundly related to the condenser temperature. The current employed determination method is introduced as a rapid and reliable method and thus, can be suggested for the quality control assessment of phytopharmaceutical semisolid preparations containing thymol and similar volatile constituents. PMID- 27193567 TI - Influenza vaccination for patients with chronic obstructive pulmonary disease: understanding immunogenicity, efficacy and effectiveness. AB - Influenza infection is an important cause of global mortality and morbidity with the greatest impact on older people and those with chronic disease. Patients with chronic obstructive pulmonary disease (COPD) are particularly vulnerable to influenza, with evidence for increased incidence and severity of infection. In this patient group influenza is associated with exacerbations and pneumonia which result in a significant healthcare burden and premature mortality. Influenza vaccination and in particular the use of the seasonal trivalent influenza vaccine (TIV) is recommended for patients with COPD. The evidence base for its effects in this population is, however, limited. Available data suggest that immunogenicity is variable in COPD but the underlying mechanisms are not completely understood. The contribution of age, disease severity, comorbidity and treatments to vaccine responses has only been investigated in a limited manner. Existing data suggest that key immune mechanisms governing T- and B-cell responses are adversely affected by these factors. The efficacy of TIV has been studied in a number of small clinical trials which form the basis of a Cochrane review. Here evidence for effect is conflicting depending on individual trial design and inclusions. Overall, TIV offers protection against influenza infection in the trial setting but further studies are required to stratify patients and enable prediction of inadequate responses. Larger-scale clinical studies have largely been observational and have often been conducted in consort with pneumonia vaccination. Overall the mortality benefit of TIV in COPD is suggested by a number studies but the impact on exacerbation prevention is less clear. Influenza vaccination currently plays an important role in disease prevention in COPD. However, we postulate that a more in-depth understanding of mechanisms of response in the context of a highly heterogeneous disease will lead to a more informed approach to vaccination and greater benefit for the individual patient. PMID- 27193569 TI - Information and communication technology demands at work: the association with job strain, effort-reward imbalance and self-rated health in different socio economic strata. AB - PURPOSE: The use of information and communication technology (ICT) is common in modern working life. ICT demands may give rise to experience of work-related stress. Knowledge about ICT demands in relation to other types of work-related stress and to self-rated health is limited. Consequently, the aim of this study was to examine the association between ICT demands and two types of work-related stress [job strain and effort-reward imbalance (ERI)] and to evaluate the association between these work-related stress measures and self-rated health, in general and in different SES strata. METHODS: This study is based on cross sectional data from the Swedish Longitudinal Occupational Survey of Health collected in 2014, from 14,873 gainfully employed people. ICT demands, job strain, ERI and self-rated health were analysed as the main measures. Sex, age, SES, lifestyle factors and BMI were used as covariates. RESULTS: ICT demands correlated significantly with the dimensions of the job strain and ERI models, especially with the demands (r = 0.42; p < 0.01) and effort (r = 0.51; p < 0.01) dimensions. ICT demands were associated with suboptimal self-rated health, also after adjustment for age, sex, SES, lifestyle and BMI (OR 1.49 [95 % CI 1.36 1.63]), but job strain (OR 1.93 [95 % CI 1.74-2.14) and ERI (OR 2.15 [95 % CI 1.95-2.35]) showed somewhat stronger associations with suboptimal self-rated health. CONCLUSION: ICT demands are common among people with intermediate and high SES and associated with job strain, ERI and suboptimal self-rated health. ICT demands should thus be acknowledged as a potential stressor of work-related stress in modern working life. PMID- 27193570 TI - The minimal sequence essential for replication and movement of Cotton leaf curl Multan betasatellite DNA by a helper virus in plant cells. AB - Betasatellites are single-stranded circular DNAs associated with a number of monopartite begomoviruses. Betasatellites rely on the helper begomoviruses for replication and movement in plant tissues and plant-to-plant transmission by vectors. Their genomes are approximately half the size of the helper viruses and consist of three main regions including the betaC1 gene, an adenine-rich (A-rich) region, and the satellite conserved region (SCR). In this study, we investigated the minimal sequences required for Cotton leaf curl Multan betasatellite (CLCuMB) replication and movement. Mutational analysis of CLCuMB DNA genome indicated that betaC1 gene and A-rich region were not required for trans-replication and movement of CLCuMB in host plants by a helper virus. Deletion of betaC1 gene and a fragment (135 nt in length) upstream of this gene impaired CLCuMB replication. However, CLCuMB mutant with deletion of betaC1 gene and a further 163 nucleotides replicated at a lower level as compared to the wild-type betasatellite. This suggests that there are essential elements in the fragment upstream of betaC1 gene, which are required for the replication of CLCuMB rather than the size limitation of CLCuMB DNA. PMID- 27193571 TI - How necessary is to analyze PTPN11 gene in fetuses with first trimester cystic hygroma and normal karyotype? AB - Cystic hygroma (CH) is a vascular-lymphatic malformation and can occur either as an isolated finding or as a part of a syndrome. The incidence of CH is about 1:1000-1:6000 births. Ultrasonographic diagnosis of CH is usually obtained in the first trimester, and the lesion can appear in septated or non-septated forms. Increased nuchal translucency and CH have been associated with a wide range of structural and genetic abnormalities. Most of CHs are associated with a number of chromosomal abnormalities especially Trisomy 21, 13, 18 and Turner syndrome. Besides, the associations between CH and non-chromosomal syndromes were also reported and Noonan Syndrome (NS) is one of the leading causes. Approximately 50% of NS cases are caused by mutations in the PTPN11 gene. A novel PTPN11 mutation defined in two separate fetuses with CH and associated with NS phenotype is being reported here. PMID- 27193572 TI - Vitamin D deficiency in an inpatient forensic intellectual disability service. AB - No research has examined vitamin D deficiency among inpatients within forensic intellectual disability services, despite their potentially increased risk. Tests of serum 25(OHD) concentration in blood are routinely offered to patients within the service as part of the admission and annual physical health check. Results were classified as deficient <25, insufficient <50, sufficient 50-75 or optimal >75. Deficient or insufficient patients were offered supplement treatment and retested within 6 months. Levels were compared between groups: level of security and gender. At baseline, 87% of patients were deficient or insufficient, whilst 13% were sufficient or optimal. At follow-up, 53% had sufficient or optimal levels. However, some patients remained deficient (13%) or insufficient (34%) due to non-compliance with treatment. Women appeared more likely to be deficient. High levels of vitamin D deficiency were found among this population. Vitamin D screening and treatment is a simple and effective way of improving the physical health of this population. PMID- 27193574 TI - If I tweet will you cite? The effect of social media exposure of articles on downloads and citations. AB - OBJECTIVES: We sought to investigate whether exposing scientific papers to social media (SM) has an effect on article downloads and citations. METHODS: We randomized all International Journal of Public Health (IJPH) original articles published between December 2012 and December 2014 to SM exposure (blog post, Twitter and Facebook) or no exposure at three different time points after first online publication. RESULTS: 130 papers (SM exposure = 65, control = 65) were randomized. The number of downloads did not differ significantly between groups (p = 0.60) nor did the number of citations (p = 0.88). Adjusting for length of observation and paper's geographical origin did not change these results. There was no difference in the number of downloads and citations between the SM exposure and control group when we stratified for open access status. The number of downloads and number of citations were significantly correlated in both groups. CONCLUSIONS: SM exposure did not have a significant effect on traditional impact metrics, such as downloads and citations. However, other metrics may measure the added value that social media might offer to a scientific journal, such as wider dissemination. PMID- 27193573 TI - Hidden burden of non-medical spending associated with inpatient care among the poor in Afghanistan. AB - OBJECTIVES: To elucidate the household payments required for medical and non medical spending for inpatient health care and examine the pattern of household payments according to household economic status and the degree of remoteness of the area of residence. METHODS: The subjects were 5490 individuals included in a nationally representative survey in 2010. Their medical (diagnosis and medicine) and non-medical (accommodation and transportation) expenses for their most recent hospitalization were analyzed. RESULTS: Compared with the richest group, the poorest group paid less for diagnosis and medicine (AOR = 0.37, P < 0.001; AOR = 0.78, P = 0.009, respectively), paid similar amounts for accommodation (AOR = 1.19, P = 0.164), and more for transportation (AOR = 2.09, P < 0.001). Residents in urban areas paid less than residents in rural areas for accommodation and transportation (AOR = 0.73, P < 0.001; AOR = 0.58, P < 0.001, respectively). CONCLUSIONS: Poor households paid less for diagnosis and medicine, but more for transportation related to inpatient care. Non-medical spending for inpatient care among the poor should be considered for affordable and accessible health-care utilization. PMID- 27193576 TI - Answers to the Letter to the Editor of H. Shantanna et al. concerning "Particulate and non-particulate steroids in spinal epidurals: a systematic review and meta-analysis" by Feeley IH, Healy EF, Noel J, Kiely PJ, Murphy TM (Eur Spine J; 2016): DOI 10.1007/s00586-016-4437-0. PMID- 27193575 TI - Impact of the Tunisian Revolution on homicide and suicide rates in Tunisia. AB - OBJECTIVES: To analyze the impact of the Tunisian Revolution on suicide and homicide patterns in Tunisia. METHODS: It is a retrospective, cross-sectional study, including all the cases of homicides and suicides that occurred during an 8-year period (2007-2014) in Northern Tunisia. We compared data before and after the revolution. RESULTS: After the revolution, the number of suicides rose 1.7 times, with a prevalence rising from 1.8 to 3.12 suicides per 100,000 persons per year. Homicides rose 1.3 times after the revolution. For both manner of death, victims were mostly males, aged between 20 and 39 years, living in urban areas. Hanging and self-immolation rose, respectively, 1.8 and 3 times after 2011. We observed suicide cases most frequently occurred in public places and in front of public administration after 2011. Homicide victims' profile and circumstances showed a single variation which is an increase in number of cases happening in rural areas. CONCLUSIONS: Our results proved a short-term impact of the transition period on homicides and suicides. Urgent preventive measures are needed especially to decrease the suicide rates. PMID- 27193577 TI - Letter to the Editor concerning "Particulate and non-particulate steroids in spinal epidurals: a systematic review and meta-analysis" by Feeley IH, Healy EF, Noel J, Kiely PJ, and Murphy TM (Eur Spine J; 2016): DOI 10.1007/s00586-016-4437 0. PMID- 27193578 TI - Major postoperative complications are associated with impaired long-term survival after gastro-esophageal and pancreatic cancer surgery: a complete national cohort study. AB - BACKGROUND: Some studies have reported an association between complications and impaired long-term survival after cancer surgery. We aimed to investigate how major complications are associated with overall survival after gastro-esophageal and pancreatic cancer surgery in a complete national cohort. METHODS: All esophageal-, gastric- and pancreatic resections performed for cancer in Norway between January 1, 2008, and December 1, 2013 were identified in the Norwegian Patient Registry together with data concerning major postoperative complications and survival. RESULTS: When emergency cases were excluded, there were 1965 esophageal-, gastric- or pancreatic resections performed for cancer in Norway between 1 January 2008, and 1 December 2013. A total of 248 patients (12.6 %) suffered major postoperative complications. Complications were associated both with increased early (90 days) mortality (OR = 4.25, 95 % CI = 2.78-6.50), and reduced overall survival when patients suffering early mortality were excluded (HR = 1.23, 95 % CI = 1.01-1.50). CONCLUSIONS: Major postoperative complications are associated with impaired long-term survival after gastro-esophageal and pancreatic cancer surgery. PMID- 27193579 TI - Molten-salt treatment of waste biomass for preparation of carbon with enhanced capacitive properties and electrocatalytic activity towards oxygen reduction. AB - Carbon powders are building blocks for electrochemical energy storage/conversion devices. Green, cost-affordable and facile preparation of carbon with applicable electrochemical properties is therefore essential for effective utilization of fluctuating renewable energy. Herein, the preparation of carbon nanoflakes via impregnation of waste biomass i.e. boiled coffee beans in molten Na2CO3-K2CO3 (with equal mass) at 800 degrees C and molten CaCl2 at 850 degrees C is reported. The microstructure and surface chemistry of the obtained carbons are specified. The correlations between synthetic conditions and microstructure/surface chemistry of the obtained carbons are rationalized. The derived carbon nanosheets are tested and compared as active materials for supercapacitors in a configuration of symmetric full cells in 1 M MeEt3NBF4 in acetonitrile and electrocatalysts towards the oxygen reduction reaction (ORR) in O2-saturated 0.1 M aqueous KOH. Despite the lower surface area, the carbon nanosheets derived in molten Na2CO3-K2CO3 exhibit enhanced capacitive properties and electrocatalytic ORR activity. The present study highlights the importance of thermal media on the microstructure, surface chemistry and electrochemistry of carbon from biomass. PMID- 27193580 TI - Applying the COM-B model to creation of an IT-enabled health coaching and resource linkage program for low-income Latina moms with recent gestational diabetes: the STAR MAMA program. AB - BACKGROUND: One of the fastest growing risk groups for early onset of diabetes is women with a recent pregnancy complicated by gestational diabetes, and for this group, Latinas are the largest at-risk group in the USA. Although evidence-based interventions, such as the Diabetes Prevention Program (DPP), which focuses on low-cost changes in eating, physical activity and weight management can lower diabetes risk and delay onset, these programs have yet to be tailored to postpartum Latina women. This study aims to tailor a IT-enabled health communication program to promote DPP-concordant behavior change among postpartum Latina women with recent gestational diabetes. The COM-B model (incorporating Capability, Opportunity, and Motivational behavioral barriers and enablers) and the Behavior Change Wheel (BCW) framework, convey a theoretically based approach for intervention development. We combined a health literacy-tailored health IT tool for reaching ethnic minority patients with diabetes with a BCW-based approach to develop a health coaching intervention targeted to postpartum Latina women with recent gestational diabetes. Current evidence, four focus groups (n = 22 participants), and input from a Regional Consortium of health care providers, diabetes experts, and health literacy practitioners informed the intervention development. Thematic analysis of focus group data used the COM-B model to determine content. Relevant cultural, theoretical, and technological components that underpin the design and development of the intervention were selected using the BCW framework. RESULTS: STAR MAMA delivers DPP content in Spanish and English using health communication strategies to: (1) validate the emotions and experiences postpartum women struggle with; (2) encourage integration of prevention strategies into family life through mothers becoming intergenerational custodians of health; and (3) increase social and material supports through referral to social networks, health coaches, and community resources. Feasibility, acceptability, and health-related outcomes (weight loss, physical activity, consumption of healthy foods, breastfeeding, and glucose screening) will be evaluated at 9 months postpartum using a randomized controlled trial design. CONCLUSIONS: STAR MAMA provides a DPP-based intervention that integrates theory-based design steps. Through systematic use of behavioral theory to inform intervention development, STAR MAMA may represent a strategy to develop health IT intervention tools to meet the needs of diverse populations. TRIAL REGISTRATION: ClinicalTrials.gov NCT02240420. PMID- 27193581 TI - Latonduine Analogs Restore F508del-Cystic Fibrosis Transmembrane Conductance Regulator Trafficking through the Modulation of Poly-ADP Ribose Polymerase 3 and Poly-ADP Ribose Polymerase 16 Activity. AB - Cystic fibrosis (CF) is a major lethal genetic disease caused by mutations in the CF transmembrane conductance regulator gene (CFTR). This encodes a chloride ion channel on the apical surface of epithelial cells. The most common mutation in CFTR (F508del-CFTR) generates a protein that is misfolded and retained in the endoplasmic reticulum. Identifying small molecules that correct this CFTR trafficking defect is a promising approach in CF therapy. However, to date only modest efficacy has been reported for correctors in clinical trials. We identified the marine sponge metabolite latonduine as a corrector. We have now developed a series of latonduine derivatives that are more potent F508del-CFTR correctors with one (MCG315 [2,3-dihydro-1H-2-benzazepin-1-one]) having 10-fold increased corrector activity and an EC50 of 72.25 nM. We show that the latonduine analogs inhibit poly-ADP ribose polymerase (PARP) isozymes 1, 3, and 16. Further our molecular modeling studies point to the latonduine analogs binding to the PARP nicotinamide-binding domain. We established the relationship between the ability of the latonduine analogs to inhibit PARP-16 and their ability to correct F508del-CFTR trafficking. We show that latonduine can inhibit both PARP-3 and -16 and that this is necessary for CFTR correction. We demonstrate that latonduine triggers correction by regulating the activity of the unfolded protein response activator inositol-requiring enzyme (IRE-1) via modulation of the level of its ribosylation by PARP-16. These results establish latonduines novel site of action as well as its proteostatic mechanism of action. PMID- 27193582 TI - Mechanisms of Action of Novel Influenza A/M2 Viroporin Inhibitors Derived from Hexamethylene Amiloride. AB - The increasing prevalence of influenza viruses with resistance to approved antivirals highlights the need for new anti-influenza therapeutics. Here we describe the functional properties of hexamethylene amiloride (HMA)-derived compounds that inhibit the wild-type and adamantane-resistant forms of the influenza A M2 ion channel. For example, 6-(azepan-1-yl)-N carbamimidoylnicotinamide ( 9: ) inhibits amantadine-sensitive M2 currents with 3 to 6-fold greater potency than amantadine or HMA (IC50 = 0.2 vs. 0.6 and 1.3 uM, respectively). Compound 9: competes with amantadine for M2 inhibition, and molecular docking simulations suggest that 9: binds at site(s) that overlap with amantadine binding. In addition, tert-butyl 4'-(carbamimidoylcarbamoyl)-2',3 dinitro-[1,1'-biphenyl]-4-carboxylate ( 27: ) acts both on adamantane-sensitive and a resistant M2 variant encoding a serine to asparagine 31 mutation (S31N) with improved efficacy over amantadine and HMA (IC50 = 0.6 uM and 4.4 uM, respectively). Whereas 9: inhibited in vitro replication of influenza virus encoding wild-type M2 (EC50 = 2.3 uM), both 27: and tert-butyl 4' (carbamimidoylcarbamoyl)-2',3-dinitro-[1,1'-biphenyl]-4-carboxylate ( 26: ) preferentially inhibited viruses encoding M2(S31N) (respective EC50 = 18.0 and 1.5 uM). This finding indicates that HMA derivatives can be designed to inhibit viruses with resistance to amantadine. Our study highlights the potential of HMA derivatives as inhibitors of drug-resistant influenza M2 ion channels. PMID- 27193584 TI - RE: Serum Lipids, Lipoproteins, and Risk of Breast Cancer: A Nested Case-Control Study Using Multiple Time Points. PMID- 27193583 TI - A PUFA-rich diet improves fat oxidation following saturated fat-rich meal. AB - PURPOSE: To determine substrate oxidation responses to saturated fatty acid (SFA) rich meals before and after a 7-day polyunsaturated fatty acid (PUFA)-rich diet versus control diet. METHODS: Twenty-six, normal-weight, adults were randomly assigned to either PUFA or control diet. Following a 3-day lead-in diet, participants completed the pre-diet visit where anthropometrics and resting metabolic rate (RMR) were measured, and two SFA-rich HF meals (breakfast and lunch) were consumed. Indirect calorimetry was used to determine fat oxidation (Fox) and energy expenditure (EE) for 4 h after each meal. Participants then consumed a PUFA-rich diet (50 % carbohydrate, 15 % protein, 35 % fat, of which 21 % of total energy was PUFA) or control diet (50 % carbohydrate, 15 % protein, 35 % fat, of which 7 % of total energy was PUFA) for the next 7 days. Following the 7-day diet, participants completed the post-diet visit. RESULTS: From pre- to post-PUFA-rich diet, there was no change in RMR (16.3 +/- 0.8 vs. 16.4 +/- 0.8 kcal/20 min) or in incremental area under the curve for EE (118.9 +/- 20.6-126.9 +/- 14.1 kcal/8h, ns). Fasting respiratory exchange ratio increased from pre- to post-PUFA-rich diet only (0.83 +/- 0.1-0.86 +/- 0.1, p < 0.05). The postprandial change in Fox increased from pre- to post-visit in PUFA-rich diet (0.03 +/- 0.1 0.23 +/- 0.1 g/15 min for cumulative Fox; p < 0.05), whereas controls showed no change. CONCLUSIONS: Adopting a PUFA-rich diet initiates greater fat oxidation after eating occasional high SFA meals compared to a control diet, an effect achieved in 7 days. PMID- 27193585 TI - Retroclival Pneumocephalus Associated with Bilateral Abducens Palsy in a Child. AB - Traumatic brain injury (TBI) is less common in children than in adults. Posterior fossa lesions are even more uncommon, but, when present, are usually epidural hematomas. These lesions, even when small, may have a bad outcome because of the possibility of compression of the important structures that the infratentorial compartment contains, such as the brainstem and cranial nerves, and the constriction of the fourth ventricle, causing acute hydrocephalus. Although unusual, posterior fossa lesions are increasingly being diagnosed because of the better quality of and easier access to cranial tomography. In this paper, we report a case of a 12-year-old male patient who had suffered a TBI and presented with several pneumocephali, one of them in the retroclival region, causing a mass effect and then compression of the sixth cranial nerve which is the most susceptible to these injuries. We discuss these traumatic posterior fossa lesions, with an emphasis on retroclival pneumocephalus, not yet described in the literature in association with bilateral abducens palsy. In addition, we discuss associated lesions and the trauma mechanism. PMID- 27193586 TI - Profile of adult and pediatric neurocysticercosis cases observed in five Southern European centers. AB - In Europe the management of neurocysticercosis (NCC) is challenging because health care providers are unaware of this condition, thus leading to diagnostic delay and mismanagement. The aim of this study is to retrospectively review the cases of NCC observed in five centers located in Florence, Negrar (Italy) and Barcelona (Spain). A total of 81 subjects with NCC were evaluated in the period 1980-2013. By applying the Del Brutto's criteria 39 cases (48.1 %) were classified as definitive cases, 31 (38.8 %) as probable cases and 11 (13.6 %) did not satisfy the diagnostic criteria. Continent of origin was known for 80 subjects. Latin America and Asia were the most frequent continents of origin (n = 37; 46.3 % and n = 22; 27.5 %) followed by Europe (n = 14; 17.5 %) and Africa (n = 7; 8.8 %). Compared with adults, paediatric patients were more likely to have eosinophilia, to have other parasitic infections, to be asymptomatic, to not be treated with antiepileptic drugs or analgesic and to heal. The study shows that there are some hurdles in the management of NCC in Europe. A not negligible portion of patients diagnosed at reference centers do not fully satisfy Del Brutto's diagnostic criteria. The higher portion of asymptomatic subjects found among the paediatric group is probably related to an ongoing serological screening among adopted children coming from endemic regions. The value of such a serological screening should be better assessed by a further cost-effective analysis. PMID- 27193588 TI - Naming no names: Comments on the taxonomy of small piroplasmids in canids. AB - Based on phylogenetic analyses, various taxonomic changes have recently been proposed for tick-transmitted small piroplasmids, including descriptions of new species. It is however essential that any such changes comply with the International Code of Zoological Nomenclature. Unfortunately, this has not been the case, and some recently proposed names are therefore invalid. The use of informal clade names is necessary until formal valid descriptions are available. PMID- 27193587 TI - Long-term whole-body vibration training in two late-onset Pompe disease patients. AB - The treatment of late-onset Pompe disease (LOPD) relies on enzyme replacement therapy (ERT) and physiotherapy but the most appropriate exercise program is not yet established. Whole-body vibration training (WBVT) has showed promising results, improving motor performances in various populations. Our aim is to assess the effects of WBVT performed by two LOPD patients in addition to ERT and physiotherapy. A side-alternating WBVT lasting 2 years; clinical assessments included: manual muscle testing (MRC sumscore), knee extension and arm flection isometric strength (multi-muscle tester M3diagnos), timed function tests (10 m walking, standing-up from chair, ascending 4-steps), 6 min walking (6 MWT), motor disability (Walton Gardner-Medwin scale), pulmonary function. Follow-up evaluations performed for 9 years since ERT start (pre-WBVT and post-WBVT) are reported for comparison. MRC sumscore improved in both patients (Pt.1:41 -> 48, Pt.2:42 -> 47) as isometric strength of knee extension (Pt.1: + 62 %, Pt.2: + 26 %) and arm flection (Pt.1: + 88 %, Pt.2: + 66 %), 6 MWT improved in Pt.1 (+75 m). Timed function tests did not greatly change. Patients reported no significant CK elevation or WBVT-related complaints. WBVT may be safely used in LOPD and seems to moderately boost muscle strength in patients receiving ERT and physiotherapy for more than 3 years. Larger cohorts should be studied to better assess WBVT potential as adjunctive exercise tool in LOPD. PMID- 27193589 TI - Backbone (1)H, (13)C and (15)N resonance assignments of the OB domain of the single stranded DNA-binding protein hSSB1 (NABP2/OBFC2B) and chemical shift mapping of the DNA-binding interface. AB - Single-stranded DNA-binding proteins (SSBs) are highly important in DNA metabolism and play an essential role in all major DNA repair pathways. SSBs are generally characterised by the presence of an oligonucleotide binding (OB) fold which is able to recognise single-stranded DNA (ssDNA) with high affinity. We discovered two news SSBs in humans (hSSB1 and hSSB2) that both contain a single OB domain followed by a divergent spacer region and a charged C-terminus. We have extensively characterised one of these, hSSB1 (NABP2/OBFC2B), in numerous important DNA processing events such as, in DNA double-stranded break repair and in the response to oxidative DNA damage. Although the structure of hSSB1 bound to ssDNA has recently been determined using X-ray crystallography, the detailed atomic level mechanism of the interaction of hSSB1 with ssDNA in solution has not been established. In this study we report the solution-state backbone chemical shift assignments of the OB domain of hSSB1. In addition, we have utilized NMR to map the DNA-binding interface of hSSB1, revealing major differences between recognition of ssDNA under physiological conditions and in the recently determined crystal structure. Our NMR data in combination with further biophysical and biochemical experiments will allow us to address these discrepancies and shed light onto the structural basis of DNA-binding by hSSB1 in solution. PMID- 27193590 TI - Letter from the New Editor-in-Chief. PMID- 27193591 TI - Genetic Characterization of Turkish Snake Melon (Cucumis melo L. subsp. melo flexuosus Group) Accessions Revealed by SSR Markers. AB - Snake melon is an important cucurbit crop especially in the Southeastern and the Mediterranean region of Turkey. It is consumed as fresh or pickled. The production is mainly done with the local landraces in the country. Turkey is one of the secondary diversification centers of melon and possesses valuable genetic resources which have different morphological characteristics in case of snake melon. Genetic diversity of snake melon genotypes collected from different regions of Turkey and reference genotypes obtained from World Melon Gene Bank in Avignon-France was examined using 13 simple sequence repeat (SSR) markers. A total of 69 alleles were detected, with an average of 5.31 alleles per locus. The polymorphism information content of SSR markers ranged from 0.19 to 0.57 (average 0.38). Based on cluster analysis, two major groups were defined. The first major group included only one accession (61), while the rest of all accessions grouped in the second major group and separated into different sub-clusters. Based on SSR markers, cluster analysis indicated that considerably high genetic variability exists among the examined accessions; however, Turkish snake melon accessions were grouped together with the reference snake melon accessions. PMID- 27193592 TI - Lessons from the fatal French study BIA-10-2474. PMID- 27193594 TI - Cognitive Psychophysiological Substrates of Affective Temperaments. AB - Affective temperaments are the subclinical manifestations or phenotypes of mood states and hypothetically represent one healthy end of the mood disorder spectrum. However, there is a scarcity of studies investigating the neurobiological basis of affective temperaments. One fundamental aspect of temperament is the behavioral reactivity to environmental stimuli, which can be effectively evaluated by use of cognitive event-related potentials (ERPs) reflecting the diversity of information processing. The aim of the present study is to explore the associations between P300 and the affective temperamental traits in healthy individuals. We recorded the P300 ERP waves using an auditory oddball paradigm in 50 medical student volunteers (23 females, 27 males). Participants' affective temperaments were evaluated using the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-auto questionnaire version (TEMPS-A). In bivariate analyses, depressive temperament score was significantly correlated with P300 latency ( rs = 0.37, P < .01). In a multiple linear regression analysis, P300 latency showed a significant positive correlation with scores of depressive temperament (beta = 0.40, P < .01) and a significant negative one with scores of cyclothymic temperament (beta = -0.29, P = .03). Affective temperament scores were not associated with P300 amplitude and reaction times. These results indicate that affective temperaments are related to information processing in the brain. Depressive temperament may be characterized by decreased physiological arousal and slower information processing, while the opposite was observed for cyclothymic temperament. PMID- 27193593 TI - Genome engineering and plant breeding: impact on trait discovery and development. AB - KEY MESSAGE: New tools for the precise modification of crops genes are now available for the engineering of new ideotypes. A future challenge in this emerging field of genome engineering is to develop efficient methods for allele mining. Genome engineering tools are now available in plants, including major crops, to modify in a predictable manner a given gene. These new techniques have a tremendous potential for a spectacular acceleration of the plant breeding process. Here, we discuss how genetic diversity has always been the raw material for breeders and how they have always taken advantage of the best available science to use, and when possible, increase, this genetic diversity. We will present why the advent of these new techniques gives to the breeders extremely powerful tools for crop breeding, but also why this will require the breeders and researchers to characterize the genes underlying this genetic diversity more precisely. Tackling these challenges should permit the engineering of optimized alleles assortments in an unprecedented and controlled way. PMID- 27193595 TI - Race, Medical Mistrust, and Segregation in Primary Care as Usual Source of Care: Findings from the Exploring Health Disparities in Integrated Communities Study. AB - Compared to White Americans, African-Americans are less likely to use primary care (PC) as their usual source of care. This is generally attributed to race differences in socioeconomic status and in access to primary care services. Little is known about the relationship between race differences in medical mistrust and the usual source of care disparity. Using data from the Exploring Health Disparities in Integrated Communities (EHDIC) study, we examined the role of medical mistrust in choosing usual source of care in 1408 black and white adults who were exposed to the same healthcare facilities and low-income racially integrated community. Multinomial logistic regression models were estimated to examine the relationship between race, medical mistrust, and usual source of care. After adjusting for demographic and health-related factors, African Americans were more likely than whites to use the emergency department (ED) (relative risk ratio [RRR] = 1.43 (95 % confidence interval (CI) [1.06-1.94])) and hospital outpatient department (RRR1.50 (95 %CI [1.10-2.05])) versus primary care as a usual source of care. When medical mistrust was added to the model, the gap between African-Americans' and whites' risk of using the ED versus primary care as a usual source of care closed (RRR = 1.29; 95 % CI [0.91-1.83]). However, race differences in the use of the hospital outpatient department remained even after accounting for medical mistrust (RRR = 1.67; 95 % CI [1.16-2.40]). Accounting for medical mistrust eliminated the ED-as-usual-source of care disparity. This study highlights the importance of medical mistrust as an intervention point for decreasing ED use as a usual source of care by low-income, urban African-Americans. PMID- 27193596 TI - Influence of cysteine 164 on active site structure in rat cysteine dioxygenase. AB - Cysteine dioxygenase is a non-heme mononuclear iron enzyme with unique structural features, namely an intramolecular thioether cross-link between cysteine 93 and tyrosine 157, and a disulfide bond between substrate L-cysteine and cysteine 164 in the entrance channel to the active site. We investigated how these posttranslational modifications affect catalysis through a kinetic, crystallographic and computational study. The enzyme kinetics of a C164S variant are identical to WT, indicating that disulfide formation at C164 does not significantly impair access to the active site at physiological pH. However, at high pH, the cysteine-tyrosine cross-link formation is enhanced in C164S. This supports the view that disulfide formation at position 164 can limit access to the active site. The C164S variant yielded crystal structures of unusual clarity in both resting state and with cysteine bound. Both show that the iron in the cysteine-bound complex is a mixture of penta- and hexa-coordinate with a water molecule taking up the final site (60 % occupancy), which is where dioxygen is believed to coordinate during turnover. The serine also displays stronger hydrogen bond interactions to a water bound to the amine of the substrate cysteine. However, the interactions between cysteine and iron appear unchanged. DFT calculations support this and show that WT and C164S have similar binding energies for the water molecule in the final site. This variant therefore provides evidence that WT also exists in an equilibrium between penta- and hexa coordinate forms and the presence of the sixth ligand does not strongly affect dioxygen binding. PMID- 27193599 TI - Giant mesenterial gastrointestinal stromal tumour mimicking a permagna hernia: a wolf in sheep's clothing. PMID- 27193597 TI - Mapping adipose and muscle tissue expression quantitative trait loci in African Americans to identify genes for type 2 diabetes and obesity. AB - Relative to European Americans, type 2 diabetes (T2D) is more prevalent in African Americans (AAs). Genetic variation may modulate transcript abundance in insulin-responsive tissues and contribute to risk; yet, published studies identifying expression quantitative trait loci (eQTLs) in African ancestry populations are restricted to blood cells. This study aims to develop a map of genetically regulated transcripts expressed in tissues important for glucose homeostasis in AAs, critical for identifying the genetic etiology of T2D and related traits. Quantitative measures of adipose and muscle gene expression, and genotypic data were integrated in 260 non-diabetic AAs to identify expression regulatory variants. Their roles in genetic susceptibility to T2D, and related metabolic phenotypes, were evaluated by mining GWAS datasets. eQTL analysis identified 1971 and 2078 cis-eGenes in adipose and muscle, respectively. Cis eQTLs for 885 transcripts including top cis-eGenes CHURC1, USMG5, and ERAP2 were identified in both tissues. 62.1 % of top cis-eSNPs were within +/-50 kb of transcription start sites and cis-eGenes were enriched for mitochondrial transcripts. Mining GWAS databases revealed association of cis-eSNPs for more than 50 genes with T2D (e.g. PIK3C2A, RBMS1, UFSP1), gluco-metabolic phenotypes (e.g. INPP5E, SNX17, ERAP2, FN3KRP), and obesity (e.g. POMC, CPEB4). Integration of GWAS meta-analysis data from AA cohorts revealed the most significant association for cis-eSNPs of ATP5SL and MCCC1 genes, with T2D and BMI, respectively. This study developed the first comprehensive map of adipose and muscle tissue eQTLs in AAs (publically accessible at https://mdsetaa.phs.wakehealth.edu ) and identified genetically regulated transcripts for delineating genetic causes of T2D, and related metabolic phenotypes. PMID- 27193600 TI - New variant of acute promyelocytic leukemia with IRF2BP2-RARA fusion. AB - We present an acute promyelocytic leukemia (APL) patient with two subtypes of IRF2BP2-RARA, in which the IRF2BP2 gene showed completely new breakpoints. Bone marrow examination revealed morphologic features indicative of APL. However, promyelocytic leukemia-RARA fusion was not detected. A paired-end mRNA sequencing followed by RT-PCR and direct sequencing revealed two types of fusion transcripts between exon 1B of IRF2BP2 and exon 3 of RARA. The patient received all-trans retinoic acid and conventional chemotherapy, but showed resistance. This is the second report of IRF2BP2 involvement in APL, and we describe various breakpoints for the IRF2BP2-RARA fusion gene. PMID- 27193598 TI - The simple neuroendocrine-immune regulatory network in oyster Crassostrea gigas mediates complex functions. AB - The neuroendocrine-immune (NEI) regulatory network is a complex system, which plays an indispensable role in the immunity of the host. In the present study, the bioinformatical analysis of the transcriptomic data from oyster Crassostrea gigas and further biological validation revealed that oyster TNF (CgTNF-1 CGI_10018786) could activate the transcription factors NF-kappaB and HSF (heat shock transcription factor) through MAPK signaling pathway, and then regulate apoptosis, redox reaction, neuro-regulation and protein folding in oyster haemocytes. The activated immune cells then released neurotransmitters including acetylcholine, norepinephrine and [Met(5)]-enkephalin to regulate the immune response by arising the expression of three TNF (CGI_10005109, CGI_10005110 and CGI_10006440) and translocating two NF-kappaB (Cgp65, CGI_10018142 and CgRel, CGI_10021567) between the cytoplasm and nuclei of haemocytes. Neurotransmitters exhibited the immunomodulation effects by influencing apoptosis and phagocytosis of oyster haemocytes. Acetylcholine and norepinephrine could down-regulate the immune response, while [Met(5)]-enkephalin up-regulate the immune response. These results suggested that the simple neuroendocrine-immune regulatory network in oyster might be activated by oyster TNF and then regulate the immune response by virtue of neurotransmitters, cytokines and transcription factors. PMID- 27193601 TI - Metastatic renal cell carcinoma imaging evaluation in the era of anti-angiogenic therapies. AB - During the last decade, the arsenal of anti-angiogenic (AAG) agents used to treat metastatic renal cell carcinoma (RCC) has grown and revolutionized the treatment of metastatic RCC, leading to improved overall survival compared to conventional chemotherapy and traditional immunotherapy agents. AAG agents include inhibitors of vascular endothelial growth factor receptor signaling pathways and mammalian target of rapamycin inhibitors. Both of these classes of targeted agents are considered cytostatic rather than cytotoxic, inducing tumor stabilization rather than marked tumor shrinkage. As a result, decreases in tumor size alone are often minimal and/or occur late in the course of successful AAG therapy, while tumor devascularization is a distinct feature of AAG therapy. In successful AAG therapy, tumor devascularization manifests on computed tomography images as a composite of a decrease in tumor size, a decrease in tumor attenuation, and the development of tumor necrosis. In this article, we review Response Evaluation Criteria in Solid Tumors (RECIST)-the current standard of care for tumor treatment response assessment which is based merely on changes in tumor length and its assessment of metastatic RCC tumor response in the era of AAG therapies. We then review the features of an ideal tumor imaging biomarker for predicting metastatic RCC response to a particular AAG agent and serving as a longitudinal tumor response assessment tool. Finally, a discussion of the more recently proposed imaging response criteria and new imaging trends in metastatic RCC response assessment will be reviewed. PMID- 27193602 TI - Bending the Cost Curve in Childhood Cancer. AB - Healthcare for children with cancer costs significantly more than other children. Cost reduction efforts aimed toward relatively small populations of patients that use a disproportionate amount of care, like childhood cancer, could have a dramatic impact on healthcare spending. The aims of this review are to provide stakeholders with an overview of the drivers of financial costs of childhood cancer and to identify possible directions to curb or decrease these costs. Costs are incurred throughout the spectrum of care. Recent trends in pharmaceutical costs, evidence identifying the contribution of administration costs, and overuse of surveillance studies are described. Awareness of cost and value, i.e., the outcome achieved per dollar or burden spent, in delivery of care and research is necessary to bend the cost curve. Incorporation of these dimensions of care requires methodology development, prioritization, and ethical balance. PMID- 27193603 TI - Allogeneic Liver Transplantation and Subsequent Syngeneic Hepatocyte Transplantation in a Rat Model: Proof of Concept for in vivo Tissue Engineering. AB - OBJECTIVES: Stable long-term functioning of liver cells after transplantation in humans is still not achieved successfully. A new approach for successful engraftment of liver cells may be the transplantation of syngeneic cells into an allogeneic liver graft. We therefore developed a new rat model for combined liver and liver cell transplantation (cLCTx) under stable immunosuppression. MATERIALS AND METHODS: After inducing a mitotic block, liver grafts from female donor rats (Dark Agouti) were transplanted into female recipients (Lewis). In male Lewis rats, liver cell proliferation was induced with subsequent cell isolation and transplantation into female recipients after organ transplantation. Y-chromosome detection of the transplanted male cells was performed by quantitative polymerase chain reaction (qPCR) and fluorescence in situ hybridization (FisH) with localization of transplanted cells by immunohistochemistry. RESULTS: Immunohistochemistry demonstrated the engraftment of transplanted cells, as confirmed by FisH, showing repopulation of the liver graft with 15.6% male cells (+/- 1.8 SEM) at day 90. qPCR revealed 14.15% (+/- 5.09 SEM) male DNA at day 90. CONCLUSION: Engraftment of transplanted syngeneic cells after cLCTx was achieved for up to 90 days under immunosuppression. Immunohistochemistry indicated cell proliferation, and the FisH results were partly confirmed by qPCR. This new protocol in rats appears feasible for addressing long-term functioning and eventually the induction of operational tolerance in the future. PMID- 27193605 TI - Disease caused by Yersinia ruckeri serotype O2b found in Chilean-farmed coho salmon, Oncorhynchus kisutch (Walbaum, 1792). PMID- 27193604 TI - Effects of light environment during growth on the expression of cone opsin genes and behavioral spectral sensitivities in guppies (Poecilia reticulata). AB - BACKGROUND: The visual system is important for animals for mate choice, food acquisition, and predator avoidance. Animals possessing a visual system can sense particular wavelengths of light emanating from objects and their surroundings and perceive their environments by processing information contained in these visual perceptions of light. Visual perception in individuals varies with the absorption spectra of visual pigments and the expression levels of opsin genes, which may be altered according to the light environments. However, which light environments and the mechanism by which they change opsin expression profiles and whether these changes in opsin gene expression can affect light sensitivities are largely unknown. This study determined whether the light environment during growth induced plastic changes in opsin gene expression and behavioral sensitivity to particular wavelengths of light in guppies (Poecilia reticulata). RESULTS: Individuals grown under orange light exhibited a higher expression of long wavelength-sensitive (LWS) opsin genes and a higher sensitivity to 600-nm light than those grown under green light. In addition, we confirmed that variations in the expression levels of LWS opsin genes were related to the behavioral sensitivities to long wavelengths of light. CONCLUSIONS: The light environment during the growth stage alters the expression levels of LWS opsin genes and behavioral sensitivities to long wavelengths of light in guppies. The plastically enhanced sensitivity to background light due to changes in opsin gene expression can enhance the detection and visibility of predators and foods, thereby affecting survival. Moreover, changes in sensitivities to orange light may lead to changes in the discrimination of orange/red colors of male guppies and might alter female preferences for male color patterns. PMID- 27193606 TI - Cereal fibre intake and risk of mortality from all causes, CVD, cancer and inflammatory diseases: a systematic review and meta-analysis of prospective cohort studies. AB - Dietary fibre intake has been associated with a lower risk of mortality; however, findings on the association of different sources of dietary fibre with mortality are conflicting. We performed a systematic review and meta-analysis of the prospective cohort studies to assess the relation between cereal fibre intake and cause-specific mortality. Medline/PubMed, SCOPUS, EMBASE, ISI web of Science and Google scholar were searched up to April 2015. Eligible prospective cohort studies were included if they provided hazard ratios (HR) or relative risks (RR) and corresponding 95 % CI for the association of cereal fibre intake and mortality from all causes, CVD, cancer and inflammatory diseases. The study specific HR were pooled by using the random-effects model. In total, fourteen prospective studies that examined the association of cereal fibre intake with mortality from all causes (n 48 052 death), CVD (n 16 882 death), cancer (n 19 489 death) and inflammatory diseases (n 1092 death) were included. The pooled adjusted HR of all-cause mortality for the highest v. the lowest category of cereal fibre intake was 0.81 (95 % CI 0.79, 0.83). Consumption of cereal fibre intake was associated with an 18 % lower risk of CVD mortality (RR 0.82; 95 % CI 0.78, 0.86). Moreover, an inverse significant association was observed between cereal fibre intake and risk of death from cancer (RR 0.85; 95 % CI 0.81, 0.89). However, no significant association was seen between cereal fibre intake and inflammation-related mortality. This meta-analysis provides further evidence that cereal fibre intake was protectively associated with mortality from all causes, CVD and cancer. PMID- 27193607 TI - Concurrent Longitudinal EPR Monitoring of Tissue Oxygenation, Acidosis, and Reducing Capacity in Mouse Xenograft Tumor Models. AB - Tissue oxygenation, extracellular acidity, and tissue reducing capacity are among crucial parameters of tumor microenvironment (TME) of significant importance for tumor pathophysiology. In this paper, we demonstrate the complementary application of particulate lithium octa-n-butoxy-naphthalocyanine and soluble nitroxide paramagnetic probes for monitoring of these TME parameters using electron paramagnetic resonance (EPR) technique. Two different types of therapeutic interventions were studied: hypothermia and systemic administration of metabolically active drug. In summary, the results demonstrate the utility of EPR technique for non-invasive concurrent longitudinal monitoring of physiologically relevant chemical parameters of TME in mouse xenograft tumor models, including that under therapeutic intervention. PMID- 27193609 TI - A Review of 3D Printing Techniques and the Future in Biofabrication of Bioprinted Tissue. AB - 3D printing has been around in the art, micro-engineering, and manufacturing worlds for decades. Similarly, research for traditionally engineered skin tissue has been in the works since the 1990s. As of recent years, the medical field also began to take advantage of the untapped potential of 3D printing for the biofabrication of tissue. To do so, researchers created a set of goals for fabricated tissues based on the characteristics of natural human tissues and organs. Fabricated tissue was then measured against this set of standards. Researchers were interested in not only creating tissue that functioned like natural tissues but in creating techniques for 3D printing that would print tissues quickly, efficiently, and ultimately result in the ability to mass produce fabricated tissues. Three promising methods of 3D printing emerged from their research: thermal inkjet printing with bioink, direct-write bioprinting, and organ printing using tissue spheroids. This review will discuss all three printing techniques, as well as their advantages, disadvantages, and the possibility of future advancements in the field of tissue fabrication. PMID- 27193608 TI - Hypoxia Augments Increased HIF-1alpha and Reduced Survival Protein p-Akt in Gelsolin (GSN)-Dependent Cardiomyoblast Cell Apoptosis. AB - Cytoskeleton filaments play an important role in cellular functions such as maintaining cell shape, cell motility, intracellular transport, and cell division. Actin-binding proteins (ABPs) have numerous functions including regulation of actin filament nucleation, elongation, severing, capping, cross linking, and actin monomer sequestration. Gelsolin (GSN) is one of the actin binding proteins. Gelsolin (GSN) is one of the actin-binding proteins that regulate cell morphology, differentiation, movement, and apoptosis. GSN also regulates cell morphology, differentiation, movement, and apoptosis. In this study, we have used H9c2 cardiomyoblast cell and H9c2-GSN stable clones to understand the roles and mechanisms of GSN overexpression in hypoxia-induced cardiomyoblast cell death. The data show that hypoxia or GSN overexpression induces HIF-1alpha expression and reduces the expression of survival markers p Akt and Bcl-2 in H9c2 cardiomyoblast cells. Under hypoxic conditions, GSN overexpression further reduces p-Akt expression and elevates total as well as cleaved GSN levels and HIF-1alpha levels. In addition, GSN overexpression enhances apoptosis in cardiomyoblasts under hypoxia. Hypoxic challenge further induced activated caspase-3 and cell death that was attenuated after GSN knock down, which implies that GSN is a critical therapeutic target against hypoxia induced cardiomyoblast cell death. PMID- 27193611 TI - A novel smart supramolecular organic gelator exhibiting dual-channel responsive sensing behaviours towards fluoride ion via gel-gel states. AB - A novel smart supramolecular organic gelator G-16 containing anion and metal coordination ability has been designed and synthesized. It shows excellent and robust gelation capability as a strong blue fluorescent supramolecular organic gel OG in DMF. Addition of Zn(2+) produced Zn(2+)-coordinated supramolecular metallogel OG-Zn. Organic gel OG and organometallic gel OG-Zn exhibited efficient and different sensing behaviors towards fluoride ion due to the variation in self assembling nature. Supramolecular metallogel OG-Zn displayed specific selectivity for fluoride ion and formed OG-Zn-F with dramatic color change from blue to blue green in solution and gel to gel states. Furthermore after directly addition of fluoride into OG produced fluoride containing organic gel OG-F with drastically modulation in color from blue to greenish yellow fluorescence via strong aggregation-induced emission (AIE) property. A number of experiments were conducted such as FTIR, (1)H NMR, and UV/Vis spectroscopies, XRD, SEM and rheology. These results revealed that the driving forces involved in self assembly of OG, OG-Zn, OG-Zn-F and OG-F were hydrogen bonding, metal coordination, pi-pi interactions, and van der Waal forces. In contrast to the most anion responsive gels, particularly fluoride ion responsive gels showed gel sol state transition on stimulation by anions, the gel state of OG and OG-Zn did not show any gel-to-sol transition during the whole F(-) response process. PMID- 27193612 TI - Isolation of human salivary extracellular vesicles by iodixanol density gradient ultracentrifugation and their characterizations. AB - Diagnostic methods that focus on the extracellular vesicles (EVs) present in saliva have been attracting great attention because of their non-invasiveness. EVs contain biomolecules such as proteins, messenger RNA (mRNA) and microRNA (miRNA), which originate from cells that release EVs, making them an ideal source for liquid biopsy. Although there have been many reports on density-based fractionation of EVs from blood and urine, the number of reports on EVs from saliva has been limited, most probably because of the difficulties in separating EVs from viscous saliva using density gradient centrifugation. This article establishes a protocol for the isolation of EVs from human saliva using density gradient centrifugation. The fractionated salivary EVs were characterized by atomic force microscopy, western blot and reverse transcription polymerase chain reaction. The results indicate that salivary EVs have a smaller diameter (47.8+/ 12.3 nm) and higher density (1.11 g/ml) than EVs isolated from conditioned cell media (74.0+/-23.5 nm and 1.06 g/ml, respectively). Additionally, to improve the throughput of density-based fractionation of EVs, the original protocol was further modified by using a fixed angle rotor instead of a swinging rotor. It was also confirmed that several miRNAs were expressed strongly in the EV-marker expressing fractions. PMID- 27193610 TI - Benefit and Risk of Tofacitinib in the Treatment of Rheumatoid Arthritis: A Focus on Herpes Zoster. AB - The biologics have revolutionized the treatment of rheumatoid arthritis (RA). However, there are still patients that are difficult to control and a cure is still not achievable. Tofacitinib, a Janus kinase (JAK) inhibitor is an orally available, new-in-class, disease-modifying anti-rheumatic drug with similar efficacy to biologics. JAK is activated by multiple cytokines involved in the pathology of RA, and affects non-immune and immune cells, mainly the lymphocytes. Besides its anti-rheumatic effect, the recent focus has been on adverse events. As with other biologics, serious infections have been observed especially with patients with lymphopenia, consistent with the mechanism of action. The major difference in adverse events from other disease-modifying anti-rheumatic drugs is the prominent increase in the occurrence of herpes zoster; it is increased worldwide, especially in Asia. There are other concerns such as malignancies and hyperlipidemia that may cause cardiovascular events that deserve further attention. The first JAK inhibitor for RA is demonstrating great benefit along with some risk, providing insights into the post-biologic era. PMID- 27193613 TI - Improving hand hygiene compliance in child daycare centres: a randomized controlled trial. AB - Gastrointestinal and respiratory infections in children attending daycare centres (DCCs) are common and compliance with hand hygiene (HH) guidelines to prevent infections is generally low. An intervention was developed to increase HH compliance and reduce infections in DCCs. The objective of this paper was to evaluate the effectiveness of this intervention on HH compliance. The intervention was evaluated in a two-arm cluster randomized controlled trial in 71 DCCs in The Netherlands. Thirty-six DCCs received the intervention including: (1) HH products; (2) training about HH guidelines; (3) two team training sessions aimed at goal setting and formulating HH improvement activities; and (4) reminders and cues for action (posters/stickers). Intervention DCCs were compared to 35 control DCCs that continued usual practice. HH compliance of caregivers and children was observed at baseline and at 1, 3 and 6 months follow-up. Using multilevel logistic regression, odds ratios (ORs) with 95% confidence intervals (CIs) were obtained for the intervention effect. Of 795 caregivers, 5042 HH opportunities for caregivers and 5606 opportunities for supervising children's HH were observed. At 1 month follow-up caregivers' compliance in intervention DCCs was 66% vs. 43% in control DCCs (OR 6.33, 95% CI 3.71-10.80), and at 6 months 59% vs. 44% (OR 4.13, 95% CI 2.33-7.32). No effect of the intervention was found on supervising children's HH (36% vs. 32%; OR 0.64, 95% CI 0.18-2.33). In conclusion, HH compliance of caregivers increased due to the intervention, therefore dissemination of the intervention can be considered. PMID- 27193614 TI - Insect Seed Predators in Erythrina falcata (Fabaceae): Identification of Predatory Species and Ecological Consequences of Asynchronous Flowering. AB - Seed predation by insects exerts negative effects on plant reproduction by limiting the supply of seeds and preventing germination. Seed predators of the family Fabaceae are usually generalists, which increases the rate of predation. One strategy to minimize seed predation, developed by plants from temperate regions, is "escape in time," i.e., flowering before or after the peak of predation. For tropical species, few studies have investigated the strategies used by plants to minimize seed predation. Here, using Erythrina falcata, a tropical species of Fabaceae, we test three main hypotheses: (i) escape in time is a mechanism used by E. falcata to minimize seed predation, (ii) the predators of E. falcata seeds are generalists, and (iii) the biometric variables of the pods can influence seed predation. In order to test these hypotheses, we determined the flowering time of E. falcata, rate of seed predation, the predators insects, and biometric variables of the pods. The analyzed trees were grouped into three classes: "early," "peak," and "late" flowering. The average seed predation rates on trees in the early and late classes were 65% and 50%, respectively, and in the peak class, 80%; thus, our first hypothesis can be accepted. Three species of Lepidoptera and two of Coleoptera were found preying on E. falcata seeds. These species were observed to be generalist predators; thus, our second hypothesis can be accepted. The biometric variables of the pods cannot influence seed predation rate. The ecological consequences of asynchronous flowering on plants and insects are discussed. PMID- 27193615 TI - Sperm Bundles in the Seminal Vesicle of the Crematogaster victima (Smith) Adult Males (Hymenoptera: Formicidae). AB - This study establishes the presence of spermatodesm in the seminal vesicles of sexually mature males of Crematogaster victima (Smith). In this species, the spermatozoa are maintained together by an extracellular matrix in which the acrosomal regions are embedded. This characteristic has not yet been observed in any other Aculeata. However, the sperm morphology in this species is similar to that described for other ants. The spermatozoa measure on average 100 MUm in length, and the number of sperm per bundle is up to 256. They are composed of a head formed by the acrosome and nucleus; this is followed by the flagellum, which is formed by the centriolar adjunct, an axoneme with a 9 + 9 + 2 microtubule pattern, two mitochondrial derivatives, and two accessory bodies. The acrosome is formed by the acrosomal vesicle and perforatorium. The nucleus is filled with compact chromatin with many areas of thick and non-compacted filaments. Both mitochondrial derivatives have the same shape and diameters. The presence of sperm bundles in sexually mature males differentiates C. victima from other ants; however, the similarities in the sperm ultrastructure support the monophyly of this insect group. PMID- 27193617 TI - Paulogramma hydarnis (n. comb.) (Nymphalidae: Biblidinae): Distribution, Systematic Position, and Conservation Status of a Rare and Endangered Butterfly. AB - The nymphalid Paulogramma hydarnis (Godart) (n. comb., previously in the genus Callicore) is an endangered butterfly present in a few montane sites in the Atlantic Forest in the Southeastern Brazil. The precise systematic position of P. hydarnis was previously unknown. Based on molecular data, we find that it is sister to Paulogramma pygas (Godart) (n. comb., also previously in Callicore), a common and widespread species in the Neotropics. In addition, we find that Callicore is not monophyletic and that "Callicore" hydarnis (along with other species) is more related to the genus Paulogramma, and should thus be placed in that genus. The genus Paulogramma is now composed by the following species: Paulogramma pyracmon (Godart), Paulogramma eunomia (Hewitson) n. comb., Paulogramma hydarnis (Godart) n. comb., Paulogramma hystaspes (Fabricius) n. comb., Paulogramma pygas (Godart) n. comb., and Paulogramma tolima (Hewitson, 1852) n. comb. Museum specimens and field data report P. hydarnis in four sites in Southeastern Brazil. Recently, P. hydarnis was recorded for the first time at Parque Nacional do Caparao, states of Espirito Santo and Minas Gerais, expanding its distribution about 200 km northward of the previously known limit. Although regularly recorded in some sites, most records are historic, before the 1960s, and the current conservation situation of this species is delicate, deserving attention. PMID- 27193616 TI - Two New Species of the Genus Xistra Bolivar (Orthoptera: Tetrigidae) from China. AB - Two new species of the tetrigid genus Xistra Bolivar from China, namely Xistra oculata Li, Deng et Zheng n. sp. and Xistra brachynota Li, Deng et Zheng n. sp. are described. An updated key to all known species of the genus is given. PMID- 27193618 TI - Three New Species of the Genus Alulatettix Liang from China (Orthoptera: Tetrigidae). AB - Characters of the tetrigid genus Alulatettix Liang are redescribed. Three new species, Alulatettix nigromarginalis n. sp., Alulatettix flavotibialis n. sp., and Alulatettix tianzhushanensis n. sp., are described. An updated key to the species of this genus is provided. PMID- 27193619 TI - Description of a New Species of Neoadoxoplatys and Immature Stages of Neoadoxoplatys saileri Kormilev (Heteroptera: Pentatomidae) Associated with Bamboo. AB - Neoadoxoplatys thomasi is described as a new species from Mexico and Venezuela. The immature stages of Neoadoxoplatys saileri Kormilev are presented for the first time. Immature stages are described and illustrated, some bamboo species of Guadua are recorded as hosts, distributional records in Mexico are also included; scanning electron micrographs of the eggs of N. saileri are provided. A key to separate the four known species of Neoadoxoplatys is included. PMID- 27193620 TI - Morphometric Variation on the Cypress Aphid Cinara cupressi (Buckton) (Hemiptera: Aphididae) Associated to Urban Trees. AB - Cinara cupressi (Buckton) is an important aphid pest of the Cupressaceae family, originally reported in Chile in 2003. Since then, it has spread over 4,000 km, contributing to conservation issues, mostly associated with native and urban trees of the Cupressaceae. In the present work, the morphometric variation of C. cupressi was examined to determine if the species present in Chile corresponds to a specific entity, and to identify variations among specimens from different localities in the study area. Colonies were collected from urban trees from northern, central, and southern Chile. Morphometric data for 14 characters in aphids from 63 localities in all the distribution ranges were measured and analyzed by multivariate analysis. Results showed that the species present in Chile corresponds to C. cupressi like a single specific entity, showing no morphological variation across the regions sampled. Our data will be discussed within the context of correct taxonomic identification for the implementation of effective biological control strategies. PMID- 27193621 TI - Allelic Variability in the Intronic Region of the Fibroin Heavy-Chain Gene in Silkworm Bombyx mori L. Strains of Brazilian Germplasm Bank. AB - The domesticated silkworm Bombyx mori L. is currently found only in germplasm banks. Therefore, characterization and conservation of this genetic resource is crucial. Based on previous studies that revealed nucleotide differences in silkworm strains, the intron of the fibroin heavy chain gene (H-fib) can be used for molecular silkworm characterization. The H-fib gene has two exons and a unique intron, and encodes the principal component of the silk fiber, the fibroin heavy chain. Therefore, this study aimed to identify the genetic variability of the unique intron of H-fib gene of 20 silkworm strains maintained at the Universidade Estadual de Maringa Brazilian Germplasm Bank (UBGB) by conformation sensitive gel electrophoresis (CSGE) and nucleotide sequencing. Genomic DNA extracted from silkworm moths was PCR amplified. CSGE revealed that most of the analyzed silkworm strains had only homoduplex molecules. However, DNA from the Japanese strains B106, B82, and M12-2 had two extra DNA fragments produced by heteroduplex molecules, revealing variation between alleles. Sequencing of the H fib intron was used to confirm the variation previously detected by CSGE and detected a significant polymorphism characterized by a 17-base pair (bp) deletion, a 2-bp insertion, and eight nucleotide substitutions. Although genetic and allelic variability was detected in some silkworm strains, the intron of the H-fib gene revealed not to be the best molecular marker for the characterization of B. mori strains from UBGB. PMID- 27193622 TI - Morphology and Distribution of Sensilla on the Antennae of Hylamorpha elegans Burmeister (Coleoptera: Scarabaeidae). AB - Considering that sensilla constitute important functional elements of sensory systems in insects, the aim of this study was to determine the type and distribution of sensilla in the antennae of Hylamorpha elegans Burmeister examined by scanning electron microscopy. Hylamorpha elegans antennae are lamellate and consist of the scape, pedicel, and flagellum. The antennal club of this beetle consists of three terminal plates: proximal, middle, and distal lamellae. Four types of sensilla were observed in the lamellae from both sexes: sensilla trichoidea, chaetica, coeloconica, and placodea. Antennal length was larger in males than in females, and significant sexual variation in the number of sensilla placodea and sensilla coeloconica was observed. PMID- 27193624 TI - Characterization of Injury Caused by Edessa meditabunda (F.), Chinavia impicticornis (Stal), and Piezodorus guildinii (West.) (Hemiptera: Pentatomidae) to Soybean. AB - Field cage trials were carried out in Ponta Grossa, Parana, season 2010/2011, aiming to characterize and evaluate the injury caused by Edessa meditabunda (F.), Chinavia impicticornis (Stal), and Piezodorus guildinii (West.) (Hemiptera: Pentatomidae) to soybean. Non-infested plants were compared with infested plants with 2 and 3 adults/m (number of adult specimens per linear meter) at the R5.1 R9, R5.3-R9, R6-R9, and R7-R9 soybean growing stages. The following variables were analyzed: foliar retention, seed germination, and injury levels estimated by the tetrazolium test. Foliar retention index ranged from 2.3 to 4.1 in plants infested with P. guildinii and from 2.6 to 3.3 in plants infested with E. meditabunda and C. impicticornis, respectively. The lowest seed germination ranged from 66.5 to 76.5% and was observed in seeds from plants infested with 2 adults of C. impicticornis at R5.3-R9 and 3 adults of P. guildinii (R5.1-R9) and E. meditabunda (R7-R9). The highest average percentage of injury level for seeds occurred with seeds from plants infested at R5.1 with 2 or 3 adults/m of P. guildinii, ranging from 22.6 to 25.0% and from 63.6 to 68.0% in the first and second trials, respectively. Edessa meditabunda caused the highest damage to the seeds of plants infested at R7 (34.0 and 41.4%), and 2 adults/m of C. impicticornis caused the highest number of damaged seeds (54.0%) in plants infested at R6. Although both species were less harmful than P. guildinii, they could be a constraint factor for grain and seed commercialization. PMID- 27193623 TI - Molecular Characterization and In Silico Analysis of the Pheromone-Binding Protein of the European Grapevine Moth Lobesia botrana (Denis & Schiffermuller) (Lepidoptera, Tortricidae). AB - The European grapevine moth Lobesia botrana (Denis & Schiffermuller) is an economically important insect in Europe. The species invaded vineyards in Chile, Argentina, and California during 2008-2010 causing severe problems. A major component of the sex pheromone, (E,Z)-7,9-dodecadienyl acetate (E7,Z9-12:Ac), is used in a mating disruption technique when grapevine moth populations are low or to monitor pest numbers. It is thought that these sexual pheromones are blends of volatiles that typically are specific to a species and are transported in the insect antenna by pheromone-binding proteins (PBPs) across the sensillar lymph to the olfactory receptors. Currently, an increasing number of Lepidopteran PBPs are being identified and cloned. However, there are no studies of the olfactory system and of proteins involved in the olfactory perception of L. botrana at the molecular level. In the present study, we report, for the first time, the sequence of a PBP from L. botrana (LbotPBP), which was determined using reverse transcription technology. Homology modeling was used to generate the three dimensional protein structure. The model suggests that PBP consists of six alpha helices as follows: Lys2-Met23 (alpha1), Thr28-Phe36 (alpha2), Arg46-Leu59 (alpha3), His70-Asn80 (alpha4), Glu84-Asn100 (alpha5), and Cys108-Lys125 (alpha6), held together by three disulfide bridges, Cys19-Cys54, Cys50-Cys108, and Cys97-Cys117. Docking simulations based on this model suggested that Trp114 is a key residue in the recognition of acetate pheromones, such as E7,Z9-12:Ac. In silico results in this study are consistent with previous findings in which E7,Z9-12:Ac acts as the most active compound in behavioral and electroantennographic assays. PMID- 27193625 TI - Ecological Characterization of White Grubs (Coleoptera: Melolonthidae) Community in Cultivated and Noncultivated Fields. AB - Comparative studies on the density and diversity of white grubs community (Coleoptera: Melolonthidae) occurring in cultivated and noncultivated fields of the Planalto region of the state of Rio Grande do Sul, Brazil, are presented. Sampling was carried out in 23 municipalities during the 2009 and 2010 winter seasons. Cultivated and noncultivated fields were chosen in each locality. Melolontid larvae were collected for identification and counted to determine the population density. A mean of 12.9 larvae m(-2) were collected in cultivated areas against 10.5 larvae m(-2) in noncultivated areas. The latter were more diverse (H' = 2.52) than cultivated areas (H' = 2.26). Despite the high evenness index (J = 0.75 noncultivated and J = 0.74 cultivated), faunistic parameters indicated Cyclocephala flavipennis Arrow and Diloboderus abderus Sturm as an extremely dominant species in cultivated areas. These results showed that the population density of white grubs increases, and their community composition is affected in cultivated areas. PMID- 27193626 TI - First Record of Mysaromima liquescens Meyric (Lepidoptera: Elaschistidae) Damaging Parica (Schizolobium parahyba var. amazonicum). AB - We report Parica as the first host recorded for Mysaromima liquescens Meyrick, and the damaging potential of M. liquescens larvae as borers in Nova Canaa do Norte, state of Mato Grosso, Brazil. PMID- 27193627 TI - Storage of Euschistus heros Eggs (Fabricius) (Hemiptera: Pentatomidae) in Liquid Nitrogen for Parasitization by Telenomus podisi Ashmead (Hymenoptera: Platygastridae). AB - Records in the literature with regard to the influence of freezing of pentatomid eggs on parasitism by microhymenopterans are scarce. In this research, we compared the storage of Euschistus heros (Fabricius) (Hemiptera: Pentatomidae) eggs in liquid nitrogen for different periods with the objective of optimizing the multiplication of Telenomus podisi Ashmead (Hymenoptera: Platygastridae) in the laboratory. Fresh eggs of E. heros were exposed (S3, S6) or not (NS3, NS6) to UV light for 30 min and stored in 1.5-mL plastic vials in liquid nitrogen either for 3 (S3, NS3) or 6 months (S6, NS6), and egg suitability to parasitoid development was compared to control eggs exposed (SC) or not (NSC) to UV treatment. Global data analysis showed that E. heros eggs stored in liquid nitrogen with or without UV treatment, for 3 or 6 months, were suitable for T. podisi parasitization. PMID- 27193629 TI - First Discovery of Polycarpine, Polycarpaurines A and C, and Their Derivatives as Novel Antiviral and Antiphytopathogenic Fungus Agents. AB - Marine natural products polycarpine, polycarpaurines A and C, and their derivatives were designed, synthesized, and characterized on the basis of (1)H NMR and mass spectroscopy. The antiviral and antiphytopathogenic fungus activities of these alkaloids were first evaluated. Polycarpine derivative 1g displayed excellent in vivo antiviral activity against TMV (inactivation inhibitory effect, 57%/500 MUg mL(-1) and 19%/100 MUg mL(-1); curative inhibitory effect, 62%/500 MUg mL(-1) and 23%/100 MUg mL(-1); and protection inhibitory effect, 56%/500 MUg mL(-1) and 29%/100 MUg mL(-1)), which is evidently higher than the activity of ribavirin (inactivation inhibitory effect, 37%/500 MUg mL( 1) and 9%/100 MUg mL(-1); curative inhibitory effect, 36%/500 MUg mL(-1) and 13%/100 MUg mL(-1); and protection inhibitory effect, 39%/500 MUg mL(-1) and 17%/100 MUg mL(-1)), thus emerging as a new lead compound for antiviral research against TMV. Fungicidal testing in vitro showed that most of the compounds displayed good fungicidal activity against plant pathogenic fungi. Further in vivo fungicidal testing indicated that compounds 6a, 6f, and 8a-c displayed good fungicidal activity. Current results provide support for the development of polycarpine alkaloids as novel agrochemicals. PMID- 27193628 TI - Comparative analysis of the integument transcriptomes of the black dilute mutant and the wild-type silkworm Bombyx mori. AB - The insect cuticle is a critical protective shell that is composed predominantly of chitin and various cuticular proteins and pigments. Indeed, insects often change their surface pigment patterns in response to selective pressures, such as threats from predators, sexual selection and environmental changes. However, the molecular mechanisms underlying the construction of the epidermis and its pigmentation patterns are not fully understood. Among Lepidoptera, the silkworm is a favorable model for color pattern research. The black dilute (bd) mutant of silkworm is the result of a spontaneous mutation; the larval body color is notably melanized. We performed integument transcriptome sequencing of the wild type strain Dazao and the mutant strains +/bd and bd/bd. In these experiments, during an early stage of the fourth molt, a stage at which approximately 51% of genes were expressed genome wide (RPKM >=1) in each strain. A total of 254 novel transcripts were characterized using Cuffcompare and BLAST analyses. Comparison of the transcriptome data revealed 28 differentially expressed genes (DEGs) that may contribute to bd larval melanism, including 15 cuticular protein genes that were remarkably highly expressed in the bd/bd mutant. We suggest that these significantly up-regulated cuticular proteins may promote melanism in silkworm larvae. PMID- 27193631 TI - Rejuvenation Biotechnology: The Industry Emerges, but Short-Termism Looms. PMID- 27193630 TI - Rule based fuzzy logic approach for classification of fibromyalgia syndrome. AB - Fibromyalgia syndrome (FMS) is a chronic muscle and skeletal system disease observed generally in women, manifesting itself with a widespread pain and impairing the individual's quality of life. FMS diagnosis is made based on the American College of Rheumatology (ACR) criteria. However, recently the employability and sufficiency of ACR criteria are under debate. In this context, several evaluation methods, including clinical evaluation methods were proposed by researchers. Accordingly, ACR had to update their criteria announced back in 1990, 2010 and 2011. Proposed rule based fuzzy logic method aims to evaluate FMS at a different angle as well. This method contains a rule base derived from the 1990 ACR criteria and the individual experiences of specialists. The study was conducted using the data collected from 60 inpatient and 30 healthy volunteers. Several tests and physical examination were administered to the participants. The fuzzy logic rule base was structured using the parameters of tender point count, chronic widespread pain period, pain severity, fatigue severity and sleep disturbance level, which were deemed important in FMS diagnosis. It has been observed that generally fuzzy predictor was 95.56 % consistent with at least of the specialists, who are not a creator of the fuzzy rule base. Thus, in diagnosis classification where the severity of FMS was classified as well, consistent findings were obtained from the comparison of interpretations and experiences of specialists and the fuzzy logic approach. The study proposes a rule base, which could eliminate the shortcomings of 1990 ACR criteria during the FMS evaluation process. Furthermore, the proposed method presents a classification on the severity of the disease, which was not available with the ACR criteria. The study was not limited to only disease classification but at the same time the probability of occurrence and severity was classified. In addition, those who were not suffering from FMS were evaluated for their conditions in other patient groups. PMID- 27193634 TI - Surgery for epilepsy: a systematic review of current evidence. AB - This seminar discusses the history and development of techniques for surgical intervention for people with refractory focal epilepsy. Published surgical success rates and prognostic factors associated with post-operative seizure freedom from individual studies have been variable and contradictory. We present here the key findings of a Cochrane systematic review of all evidence published since the introduction of magnetic resonance imaging (MRI) to pre-operative surgical assessment in 1984. Our findings show the usefulness of uncontrolled case series is now past. Future studies with a prospective controlled design should focus on specific research questions to help improve results and provide better-informed advice. PMID- 27193635 TI - Label-free analysis of mRNA capping efficiency using RNase H probes and LC-MS. AB - A label-free method for determining the 5'-end cap identity and orientation of a messenger RNA (mRNA) is described. Biotin-tagged probes that were complementary to the 5' end of target mRNA were used with RNase H to cleave the 5' end of the mRNA. The cleaved end sequence was isolated using streptavidin-coated magnetic beads and then analyzed by LC-MS. Quantitative and qualitative information on the 5' cap was determined from the unique mass of the isolated cleaved sequence. This approach, combined with the use of 5' RNA pyrophosphohydrolase, was also used to ascertain the orientation of the 5' cap. The assay showed low-picomole sensitivity for detecting capping reaction impurities. Uncapped triphosphate mRNA, spiked into 100 pmol of capped mRNA, could be detected over the tested range of 0.5 to 25 % with a linear response. The capping efficiency of several vaccinia-capped mRNA preparations was determined to be between 88 and 98 % depending on the modification type and length of the mRNA. mRNA of 2.2K and 9K nucleotides in length and containing the modified nucleotides pseudouridine and 5 methylcytidine were all successfully analyzed, demonstrating the utility of the technique to study mRNA capping. Graphical abstract mRNA 5' end analysis with RNAse H cleavage and capture probe. PMID- 27193636 TI - An All-Solid-State Fiber-Shaped Aluminum-Air Battery with Flexibility, Stretchability, and High Electrochemical Performance. AB - Owing to the high theoretical energy density of metal-air batteries, the aluminum air battery has been proposed as a promising long-term power supply for electronics. However, the available energy density from the aluminum-air battery is far from that anticipated and is limited by current electrode materials. Herein we described the creation of a new family of all-solid-state fiber-shaped aluminum-air batteries with a specific capacity of 935 mAh g(-1) and an energy density of 1168 Wh kg(-1) . The synthesis of an electrode composed of cross stacked aligned carbon-nanotube/silver-nanoparticle sheets contributes to the remarkable electrochemical performance. The fiber shape also provides the aluminum-air batteries with unique advantages; for example, they are flexible and stretchable and can be woven into a variety of textiles for large-scale applications. PMID- 27193637 TI - The genetic evolution of skin squamous cell carcinoma: tumor suppressor identity matters. PMID- 27193639 TI - Zika must remain a high priority. PMID- 27193640 TI - Second thoughts. PMID- 27193638 TI - Malignant isolated cortical vein thrombosis with type II protein S deficiency: a case report. AB - BACKGROUND: The incidence of cerebral venous thrombosis (CVT) is low, and in particular, isolated cortical vein thrombosis (ICVT) is very rare. The diagnosis of ICVT is difficult by using conventional computed tomography (CT) and magnetic resonance imaging (MRI). However, with appropriate treatment, ICVT has a good prognosis. CASE PRESENTATION: Herein, we present a rare case of a 40-year-old woman with ICVT and type II protein S (PS) deficiency, who experienced a stroke. She initially presented with generalized convulsions. A CT scan showed intracerebral hemorrhage (ICH) in the left temporoparietal region. However, her condition rapidly deteriorated and she went into a coma approximately 20 h after admission. A second CT scan revealed significant ICH expansion and transfalcine herniation. Decompressive hemicraniectomy with duraplasty was performed, and ICVT was confirmed owing to abnormal vascular tone and black appearance of the cortical vein. She underwent anticoagulation therapy and rehabilitation, and gradually recovered. CONCLUSION: We experienced an extremely rare case of isolated cortical vein thrombosis related with type II PS deficiency. CT-digital subtraction angiography is a useful supportive technique in the diagnosis of ICVT. Decompressive hemicraniectomy is effective for hemorrhage extension cases, and ICVT with hemorrhage might require early anticoagulation therapy. PMID- 27193641 TI - Open medicine. PMID- 27193642 TI - Teach students the biology of their time. PMID- 27193654 TI - Gridlock over Italy's olive tree deaths starts to ease. PMID- 27193655 TI - Demotion of science ministry angers beleaguered Brazilian researchers. PMID- 27193656 TI - Boaty McBoatfleet: British ship joins wave of rugged polar vessels. PMID- 27193657 TI - Mirror-image enzyme copies looking-glass DNA. PMID- 27193658 TI - Bankruptcy filing worries developers of nanoparticle cancer drugs. PMID- 27193659 TI - Mixed-up metals make for stronger, tougher, stretchier alloys. PMID- 27193660 TI - The race to create super-crops. PMID- 27193661 TI - Policy: Global standards for stem-cell research. PMID- 27193662 TI - Twelve principles for open innovation 2.0. PMID- 27193663 TI - Correction. PMID- 27193666 TI - Arts: California on camera. PMID- 27193667 TI - China: Prevent misuse of eco-compensation. PMID- 27193668 TI - Alien species: EU list should add potential invasives. PMID- 27193669 TI - Scientific record: Speed publication of self-corrections. PMID- 27193670 TI - Pollution: Clean up the air in Kathmandu. PMID- 27193671 TI - Transport: Nicaragua Canal may not benefit shipping. PMID- 27193672 TI - Harry Elderfield (1943-2016). PMID- 27193673 TI - Neuroscience: Virtual reality explored. PMID- 27193674 TI - Drug discovery: Fighting evolution with chemical synthesis. PMID- 27193675 TI - Neutrino physics: A deliberate mix-up in flavour. PMID- 27193676 TI - Astrophysics: Illuminating brown dwarfs. PMID- 27193677 TI - Structural biology: Snapshots of transcription initiation. PMID- 27193678 TI - Reproducible pharmacogenomic profiling of cancer cell line panels. AB - The use of large-scale genomic and drug response screening of cancer cell lines depends crucially on the reproducibility of results. Here we consider two previously published screens, plus a later critique of these studies. Using independent data, we show that consistency is achievable, and provide a systematic description of the best laboratory and analysis practices for future studies. PMID- 27193679 TI - A platform for the discovery of new macrolide antibiotics. AB - The chemical modification of structurally complex fermentation products, a process known as semisynthesis, has been an important tool in the discovery and manufacture of antibiotics for the treatment of various infectious diseases. However, many of the therapeutics obtained in this way are no longer effective, because bacterial resistance to these compounds has developed. Here we present a practical, fully synthetic route to macrolide antibiotics by the convergent assembly of simple chemical building blocks, enabling the synthesis of diverse structures not accessible by traditional semisynthetic approaches. More than 300 new macrolide antibiotic candidates, as well as the clinical candidate solithromycin, have been synthesized using our convergent approach. Evaluation of these compounds against a panel of pathogenic bacteria revealed that the majority of these structures had antibiotic activity, some efficacious against strains resistant to macrolides in current use. The chemistry we describe here provides a platform for the discovery of new macrolide antibiotics and may also serve as the basis for their manufacture. PMID- 27193680 TI - Structure of the T4 baseplate and its function in triggering sheath contraction. AB - Several systems, including contractile tail bacteriophages, the type VI secretion system and R-type pyocins, use a multiprotein tubular apparatus to attach to and penetrate host cell membranes. This macromolecular machine resembles a stretched, coiled spring (or sheath) wound around a rigid tube with a spike-shaped protein at its tip. A baseplate structure, which is arguably the most complex part of this assembly, relays the contraction signal to the sheath. Here we present the atomic structure of the approximately 6-megadalton bacteriophage T4 baseplate in its pre- and post-host attachment states and explain the events that lead to sheath contraction in atomic detail. We establish the identity and function of a minimal set of components that is conserved in all contractile injection systems and show that the triggering mechanism is universally conserved. PMID- 27193681 TI - Transcription initiation complex structures elucidate DNA opening. AB - Transcription of eukaryotic protein-coding genes begins with assembly of the RNA polymerase (Pol) II initiation complex and promoter DNA opening. Here we report cryo-electron microscopy (cryo-EM) structures of yeast initiation complexes containing closed and open DNA at resolutions of 8.8 A and 3.6 A, respectively. DNA is positioned and retained over the Pol II cleft by a network of interactions between the TATA-box-binding protein TBP and transcription factors TFIIA, TFIIB, TFIIE, and TFIIF. DNA opening occurs around the tip of the Pol II clamp and the TFIIE 'extended winged helix' domain, and can occur in the absence of TFIIH. Loading of the DNA template strand into the active centre may be facilitated by movements of obstructing protein elements triggered by allosteric binding of the TFIIE 'E-ribbon' domain. The results suggest a unified model for transcription initiation with a key event, the trapping of open promoter DNA by extended protein-protein and protein-DNA contacts. PMID- 27193683 TI - An irradiated brown-dwarf companion to an accreting white dwarf. AB - Interacting compact binary systems provide a natural laboratory in which to study irradiated substellar objects. As the mass-losing secondary (donor) in these systems makes a transition from the stellar to the substellar regime, it is also irradiated by the primary (compact accretor). The internal and external energy fluxes are both expected to be comparable in these objects, providing access to an unexplored irradiation regime. The atmospheric properties of donors are largely unknown, but could be modified by the irradiation. To constrain models of donor atmospheres, it is necessary to obtain accurate observational estimates of their physical properties (masses, radii, temperatures and albedos). Here we report the spectroscopic detection and characterization of an irradiated substellar donor in an accreting white-dwarf binary system. Our near-infrared observations allow us to determine a model-independent mass estimate for the donor of 0.055 +/- 0.008 solar masses and an average spectral type of L1 +/- 1, supporting both theoretical predictions and model-dependent observational constraints that suggest that the donor is a brown dwarf. Our time-resolved data also allow us to estimate the average irradiation-induced temperature difference between the dayside and nightside of the substellar donor (57 kelvin) and the maximum difference between the hottest and coolest parts of its surface (200 kelvin). The observations are well described by a simple geometric reprocessing model with a bolometric (Bond) albedo of less than 0.54 at the 2sigma confidence level, consistent with high reprocessing efficiency, but poor lateral heat redistribution in the atmosphere of the brown-dwarf donor. These results add to our knowledge of binary evolution, in that the donor has survived the transition from the stellar to the substellar regime, and of substellar atmospheres, in that we have been able to test a regime in which the irradiation and the internal energy of a brown dwarf are comparable. PMID- 27193684 TI - Repeated large-scale retreat and advance of Totten Glacier indicated by inland bed erosion. AB - Climate variations cause ice sheets to retreat and advance, raising or lowering sea level by metres to decametres. The basic relationship is unambiguous, but the timing, magnitude and sources of sea-level change remain unclear; in particular, the contribution of the East Antarctic Ice Sheet (EAIS) is ill defined, restricting our appreciation of potential future change. Several lines of evidence suggest possible collapse of the Totten Glacier into interior basins during past warm periods, most notably the Pliocene epoch, causing several metres of sea-level rise. However, the structure and long-term evolution of the ice sheet in this region have been understood insufficiently to constrain past ice sheet extents. Here we show that deep ice-sheet erosion-enough to expose basement rocks-has occurred in two regions: the head of the Totten Glacier, within 150 kilometres of today's grounding line; and deep within the Sabrina Subglacial Basin, 350-550 kilometres from this grounding line. Our results, based on ICECAP aerogeophysical data, demarcate the marginal zones of two distinct quasi-stable EAIS configurations, corresponding to the 'modern-scale' ice sheet (with a marginal zone near the present ice-sheet margin) and the retreated ice sheet (with the marginal zone located far inland). The transitional region of 200-250 kilometres in width is less eroded, suggesting shorter-lived exposure to eroding conditions during repeated retreat-advance events, which are probably driven by ocean-forced instabilities. Representative ice-sheet models indicate that the global sea-level increase resulting from retreat in this sector can be up to 0.9 metres in the modern-scale configuration, and exceeds 2 metres in the retreated configuration. PMID- 27193682 TI - Near-atomic resolution visualization of human transcription promoter opening. AB - In eukaryotic transcription initiation, a large multi-subunit pre-initiation complex (PIC) that assembles at the core promoter is required for the opening of the duplex DNA and identification of the start site for transcription by RNA polymerase II. Here we use cryo-electron microscropy (cryo-EM) to determine near atomic resolution structures of the human PIC in a closed state (engaged with duplex DNA), an open state (engaged with a transcription bubble), and an initially transcribing complex (containing six base pairs of DNA-RNA hybrid). Our studies provide structures for previously uncharacterized components of the PIC, such as TFIIE and TFIIH, and segments of TFIIA, TFIIB and TFIIF. Comparison of the different structures reveals the sequential conformational changes that accompany the transition from each state to the next throughout the transcription initiation process. This analysis illustrates the key role of TFIIB in transcription bubble stabilization and provides strong structural support for a translocase activity of XPB. PMID- 27193685 TI - Deep-sea diversity patterns are shaped by energy availability. AB - The deep ocean is the largest and least-explored ecosystem on Earth, and a uniquely energy-poor environment. The distribution, drivers and origins of deep sea biodiversity remain unknown at global scales. Here we analyse a database of more than 165,000 distribution records of Ophiuroidea (brittle stars), a dominant component of sea-floor fauna, and find patterns of biodiversity unlike known terrestrial or coastal marine realms. Both patterns and environmental predictors of deep-sea (2,000-6,500 m) species richness fundamentally differ from those found in coastal (0-20 m), continental shelf (20-200 m), and upper-slope (200 2,000 m) waters. Continental shelf to upper-slope richness consistently peaks in tropical Indo-west Pacific and Caribbean (0-30 degrees ) latitudes, and is well explained by variations in water temperature. In contrast, deep-sea species show maximum richness at higher latitudes (30-50 degrees ), concentrated in areas of high carbon export flux and regions close to continental margins. We reconcile this structuring of oceanic biodiversity using a species-energy framework, with kinetic energy predicting shallow-water richness, while chemical energy (export productivity) and proximity to slope habitats drive deep-sea diversity. Our findings provide a global baseline for conservation efforts across the sea floor, and demonstrate that deep-sea ecosystems show a biodiversity pattern consistent with ecological theory, despite being different from other planetary-scale habitats. PMID- 27193686 TI - Local fitness landscape of the green fluorescent protein. AB - Fitness landscapes depict how genotypes manifest at the phenotypic level and form the basis of our understanding of many areas of biology, yet their properties remain elusive. Previous studies have analysed specific genes, often using their function as a proxy for fitness, experimentally assessing the effect on function of single mutations and their combinations in a specific sequence or in different sequences. However, systematic high-throughput studies of the local fitness landscape of an entire protein have not yet been reported. Here we visualize an extensive region of the local fitness landscape of the green fluorescent protein from Aequorea victoria (avGFP) by measuring the native function (fluorescence) of tens of thousands of derivative genotypes of avGFP. We show that the fitness landscape of avGFP is narrow, with 3/4 of the derivatives with a single mutation showing reduced fluorescence and half of the derivatives with four mutations being completely non-fluorescent. The narrowness is enhanced by epistasis, which was detected in up to 30% of genotypes with multiple mutations and mostly occurred through the cumulative effect of slightly deleterious mutations causing a threshold-like decrease in protein stability and a concomitant loss of fluorescence. A model of orthologous sequence divergence spanning hundreds of millions of years predicted the extent of epistasis in our data, indicating congruence between the fitness landscape properties at the local and global scales. The characterization of the local fitness landscape of avGFP has important implications for several fields including molecular evolution, population genetics and protein design. PMID- 27193689 TI - No observable conformational changes in PSII. PMID- 27193690 TI - The interaction of Hg(2+) and trivalent ions with two new fluorescein bio inspired dual colorimetric/fluorimetric probes. AB - Two new luminescent compounds containing fluorescein-amino acid units have been designed and synthesized via an ester linkage between a fluorescein ethyl ester and Boc-Ser(TBDMS)-OH or Boc-Cys(4-MeBzl)-OH, and their photophysical properties have been explored. The optical response of both compounds (2 and 3) towards the metal ions Na(+), K(+), Hg(+), Ag(+), Ca(2+), Co(2+), Ni(2+), Cu(2+), Zn(2+), Cd(2+), Pb(2+), Hg(2+), Al(3+), Fe(3+), Ga(3+)and Cr(3+) was investigated in pure acetonitrile and in acetonitrile/water mixtures. A strong CHEF (Chelation Enhanced Fluorescence) effect was observed with all the trivalent metals and Hg(2+) ions in both solvents. UV-vis absorption, steady state and time resolved emission spectroscopy methods were employed. The results show the formation of mononuclear complexes with Al(3+), Fe(3+), Ga(3+), Cr(3+), and Hg(2+). Theoretical calculation using Density Functional Theory was performed in order to obtain atomistic insights into the coordination geometry of Al(3+) and Hg(2+) to the fluorescein 3, which is in accordance with the experimental stoichiometry results obtained in the Job's plot method. Among the active cations, the minimum detectable amount is under 1 MUM for most of the cases in both absorption and fluorescence spectroscopy methods. PMID- 27193691 TI - Genetically diverse CC-founder mouse strains replicate the human influenza gene expression signature. AB - Influenza A viruses (IAV) are zoonotic pathogens that pose a major threat to human and animal health. Influenza virus disease severity is influenced by viral virulence factors as well as individual differences in host response. We analyzed gene expression changes in the blood of infected mice using a previously defined set of signature genes that was derived from changes in the blood transcriptome of IAV-infected human volunteers. We found that the human signature was reproduced well in the founder strains of the Collaborative Cross (CC) mice, thus demonstrating the relevance and importance of mouse experimental model systems for studying human influenza disease. PMID- 27193687 TI - An obligatory role for neurotensin in high-fat-diet-induced obesity. AB - Obesity and its associated comorbidities (for example, diabetes mellitus and hepatic steatosis) contribute to approximately 2.5 million deaths annually and are among the most prevalent and challenging conditions confronting the medical profession. Neurotensin (NT; also known as NTS), a 13-amino-acid peptide predominantly localized in specialized enteroendocrine cells of the small intestine and released by fat ingestion, facilitates fatty acid translocation in rat intestine, and stimulates the growth of various cancers. The effects of NT are mediated through three known NT receptors (NTR1, 2 and 3; also known as NTSR1, 2, and NTSR3, respectively). Increased fasting plasma levels of pro-NT (a stable NT precursor fragment produced in equimolar amounts relative to NT) are associated with increased risk of diabetes, cardiovascular disease and mortality; however, a role for NT as a causative factor in these diseases is unknown. Here we show that NT-deficient mice demonstrate significantly reduced intestinal fat absorption and are protected from obesity, hepatic steatosis and insulin resistance associated with high fat consumption. We further demonstrate that NT attenuates the activation of AMP-activated protein kinase (AMPK) and stimulates fatty acid absorption in mice and in cultured intestinal cells, and that this occurs through a mechanism involving NTR1 and NTR3 (also known as sortilin). Consistent with the findings in mice, expression of NT in Drosophila midgut enteroendocrine cells results in increased lipid accumulation in the midgut, fat body, and oenocytes (specialized hepatocyte-like cells) and decreased AMPK activation. Remarkably, in humans, we show that both obese and insulin-resistant subjects have elevated plasma concentrations of pro-NT, and in longitudinal studies among non-obese subjects, high levels of pro-NT denote a doubling of the risk of developing obesity later in life. Our findings directly link NT with increased fat absorption and obesity and suggest that NT may provide a prognostic marker of future obesity and a potential target for prevention and treatment. PMID- 27193693 TI - PANTHER-PSEP: predicting disease-causing genetic variants using position-specific evolutionary preservation. AB - PANTHER-PSEP is a new software tool for predicting non-synonymous genetic variants that may play a causal role in human disease. Several previous variant pathogenicity prediction methods have been proposed that quantify evolutionary conservation among homologous proteins from different organisms. PANTHER-PSEP employs a related but distinct metric based on 'evolutionary preservation': homologous proteins are used to reconstruct the likely sequences of ancestral proteins at nodes in a phylogenetic tree, and the history of each amino acid can be traced back in time from its current state to estimate how long that state has been preserved in its ancestors. Here, we describe the PSEP tool, and assess its performance on standard benchmarks for distinguishing disease-associated from neutral variation in humans. On these benchmarks, PSEP outperforms not only previous tools that utilize evolutionary conservation, but also several highly used tools that include multiple other sources of information as well. For predicting pathogenic human variants, the trace back of course starts with a human 'reference' protein sequence, but the PSEP tool can also be applied to predicting deleterious or pathogenic variants in reference proteins from any of the ~100 other species in the PANTHER database. AVAILABILITY AND IMPLEMENTATION: PANTHER-PSEP is freely available on the web at http://pantherdb.org/tools/csnpScoreForm.jsp Users can also download the command line based tool at ftp://ftp.pantherdb.org/cSNP_analysis/PSEP/ CONTACT: pdthomas@usc.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 27193694 TI - Nucleophilic Iododifluoromethylation of Carbonyl Compounds Using Difluoromethyl 2 Pyridyl Sulfone. AB - A new, efficient method for iododifluoromethylation of carbonyl compounds utilizing difluoromethyl 2-pyridyl sulfone (2-PySO2CF2H) is described. This transformation is achieved by a nucleophilic addition of 2-PySO2CF2H with carbonyl compounds and a subsequent iodination of sulfinate, which is generated in situ by a novel zinc-mediated depyridination reaction. The method employs mild reaction conditions, exhibits excellent functional-group tolerance, and can be used in the synthesis of various iododifluoromethylated carbinols. PMID- 27193695 TI - Compared to femoral venous access, upper extremity right heart catheterization reduces time to ambulation: A single center experience. AB - OBJECTIVES: To determine ambulation times after right heart catheterization (RHC) via upper extremity access compared to femoral venous access. BACKGROUND: Transradial coronary angiography has been associated with shorter times to ambulation. We hypothesized that RHC from the upper extremity would be similarly associated with shorter ambulation times when compared to traditional femoral access. METHODS: We performed a single-center retrospective analysis of 379 consecutive patients who underwent a variety of diagnostic and interventional left- and right-heart procedures through upper extremity and femoral access sites. RESULTS: The time to ambulation for RHC through the arm veins versus the femoral vein was lower (42.6 min +/- 14.2 vs. 175.0 min +/- 65.0, P < 0.001). Fluoroscopy times (8.5 min +/- 6.8 vs. 12.8 min +/- 8.4, P < 0.001) and radiation doses (64.1 Gy cm-2 +/- 60.0 vs. 108.5 Gy cm-2 +/- 71.6, P < 0.001) were reduced in the radial compared to femoral group, respectively. In multivariate analyses, upper arm access (P < 0.0001), lower heparin dose (P = 0.032), inpatient status (P = 0.01), and concurrent PCI (P = 0.03) were associated with shorter times to ambulation. CONCLUSIONS: Right heart catheterization from the upper extremity is strongly associated with shorter times to ambulation. (c) 2016 Wiley Periodicals, Inc. PMID- 27193692 TI - Microsurgical resection of pineal region tumors. AB - The extensive variety of possible histologic subtypes makes it imperative to establish a tissue diagnosis in patients with pineal region tumors. Management decisions regarding adjuvant therapy, prognosis, and follow-up strategies vary with the histologic diagnosis. Specialized surgical and stereotactic techniques have evolved to provide the neurosurgeon with an array of safe and effective options for obtaining a tissue diagnosis. Advanced microsurgical techniques combined with improved preoperative management and postoperative critical care methods have made aggressive surgical resection a mainstay of management. Aggressive surgical resection has resulted in excellent long-term prognoses for nearly all patients with benign tumors and a large percentage of patients with malignant tumors. However, pineal region surgery remains fraught with potential pitfalls, and these favorable results are dependent on an advanced level of surgical expertise. PMID- 27193696 TI - Triclosan-induced genes Rv1686c-Rv1687c and Rv3161c are not involved in triclosan resistance in Mycobacterium tuberculosis. AB - A key issue towards developing new chemotherapeutic approaches to fight Mycobacterium tuberculosis is to understand the mechanisms underlying drug resistance. Previous studies have shown that genes Rv1686c-Rv1687c and Rv3161c, predicted to encode an ATP-binding cassette transporter and a dioxygenase respectively, are induced in the presence of triclosan and other antimicrobial compounds. Therefore a possible role in drug resistance has been suggested for the products of these genes although no functional studies have been done. The aim of the present study was to clarify the role of Rv1686c-Rv1687c and Rv3161c in M. tuberculosis resistance to triclosan and other drugs. To this end, deficient mutants and overproducing strains for both systems were constructed and their minimal inhibitory concentration (MIC) against over 20 compounds, including triclosan, was evaluated. Unexpectedly, no differences between the MIC of these strains and the wild-type H37Rv were observed for any of the compounds tested. Moreover the MIC of triclosan was not affected by efflux pump inhibitors that inhibit the activity of transporters similar to the one encoded by Rv1686c Rv1687c. These results suggest that none of the two systems is directly involved in M. tuberculosis resistance to triclosan or to any of the antimicrobials tested. PMID- 27193698 TI - Sunlight as an energetic driver in the synthesis of molecules necessary for life. AB - Solar radiation was overwhelmingly the largest source of energy on the early Earth. Energy provided by the Sun has the potential to access different chemistries than energy provided by other sources, such as hydrothermal vents, because of the unique characteristics of photochemistry that differentiate it from conventional thermal chemistry. This review considers how sunlight-driven reactions can abiotically generate prebiotic molecules necessary for the evolution of life. We discuss briefly the characteristics of the early Sun and the likely environmental conditions on the early Earth because photochemistry is both environment- and molecule-specific. An overview of the fundamental principles of photophysics and photochemistry is followed by discussion of a selection of prebiotically-relevant examples of photochemical reactions, focusing on syntheses that lead to the production of cellular components (e.g. sugars, lipids, and biopolymer precursors). The role of photostability as an evolutionary driving force is also considered. These examples highlight the ability of simple organic molecules to harness solar energy and convert it into high-energy chemical bonds, generating molecular complexity. PMID- 27193697 TI - The Contribution of Skilled Nursing Facilities to Hospitals' Readmission Rate. AB - OBJECTIVE: To examine the relative influence of hospital and skilled nursing facilities (SNFs) on 30-day rehospitalization. DATA SOURCES/SETTINGS: Elderly Medicare beneficiaries newly admitted to a SNF following hospitalization. STUDY DESIGN: We ranked hospitals and SNFs into quartiles based on previous years' adjusted rehospitalization rates (ARRs) and examined how rehospitalizations from a given hospital vary depending upon the admitting SNF ARR quartile. We examined whether the availability of SNFs with low rehospitalization rates influenced hospitals' SNF readmission rates and whether changes in a hospital's ARR over 3 years is associated with changes in the SNFs to which they discharge. PRINCIPAL FINDINGS: Hospital readmission rates from SNFs varied 5 percentage points between patients discharged to SNFs in the lowest and the highest rehospitalization quartiles. Low rehospitalization rate hospitals sent a larger fraction of their patients to the lowest rehospitalization SNFs available in the area. A 10 percent increase in hospital's share of discharges to the lowest rehospitalization quartile SNFs is associated with a 1 percentage point reduction in hospital's ARR. CONCLUSIONS: The SNF rehospitalization rate has greater influence on patients' risk of rehospitalization than the discharging hospital. Identifying high-performing SNFs may be a powerful strategy for hospitals to reduce rehospitalizations. PMID- 27193699 TI - Multiple post-domestication origins of kabuli chickpea through allelic variation in a diversification-associated transcription factor. AB - Chickpea (Cicer arietinum) is among the founder crops domesticated in the Fertile Crescent. One of two major forms of chickpea, the so-called kabuli type, has white flowers and light-colored seed coats, properties not known to exist in the wild progenitor. The origin of the kabuli form has been enigmatic. We genotyped a collection of wild and cultivated chickpea genotypes with 538 single nucleotide polymorphisms (SNPs) and examined patterns of molecular diversity relative to geographical sources and market types. In addition, we examined sequence and expression variation in candidate anthocyanin biosynthetic pathway genes. A reduction in genetic diversity and extensive genetic admixture distinguish cultivated chickpea from its wild progenitor species. Among germplasm, the kabuli form is polyphyletic. We identified a basic helix-loop-helix (bHLH) transcription factor at chickpea's B locus that conditions flower and seed colors, orthologous to Mendel's A gene of garden pea, whose loss of function is associated invariantly with the kabuli type of chickpea. From the polyphyletic distribution of the kabuli form in germplasm, an absence of nested variation within the bHLH gene and invariant association of loss of function of bHLH among the kabuli type, we conclude that the kabuli form arose multiple times during the phase of phenotypic diversification after initial domestication of cultivated chickpea. PMID- 27193700 TI - High-energy side-peak emission of exciton-polariton condensates in high density regime. AB - In a standard semiconductor laser, electrons and holes recombine via stimulated emission to emit coherent light, in a process that is far from thermal equilibrium. Exciton-polariton condensates-sharing the same basic device structure as a semiconductor laser, consisting of quantum wells coupled to a microcavity-have been investigated primarily at densities far below the Mott density for signatures of Bose-Einstein condensation. At high densities approaching the Mott density, exciton-polariton condensates are generally thought to revert to a standard semiconductor laser, with the loss of strong coupling. Here, we report the observation of a photoluminescence sideband at high densities that cannot be accounted for by conventional semiconductor lasing. This also differs from an upper-polariton peak by the observation of the excitation power dependence in the peak-energy separation. Our interpretation as a persistent coherent electron-hole-photon coupling captures several features of this sideband, although a complete understanding of the experimental data is lacking. A full understanding of the observations should lead to a development in non equilibrium many-body physics. PMID- 27193703 TI - N-acyl dopamines induce cell death in PC12 cell line via induction of nitric oxide generation and oxidative stress. AB - It was shown that dopamine amides of arachidonic, oleic, and docosahexaenoic acids exhibit toxicity with respect to PC12 pheochromocytoma cell line. The mechanism of realization of the cytotoxic effect of acyl dopamines is the induction of oxidative stress. This event is preceded by triggering the synthesis of nitric oxide. PMID- 27193705 TI - New family of pectinase genes PGU1b-PGU3b of the pectinolytic yeast Saccharomyces bayanus var. uvarum. AB - Using yeast genome databases and literature data, we have conducted a phylogenetic analysis of pectinase PGU genes from Saccharomyces strains assigned to the biological species S. arboricola, S. bayanus (var. uvarum), S. cariocanus, S. cerevisiae, S. kudriavzevii, S. mikatae, S. paradoxus, and hybrid taxon S. pastorianus (syn. S. carlsbergensis). Single PGU genes were observed in all Saccharomyces species, except S. bayanus. The superfamily of divergent PGU genes has been documented in S. bayanus var. uvarum for the first time. Chromosomal localization of new PGU1b, PGU2b, and PGU3b genes in the yeast S. bayanus var. uvarum has been determined by molecular karyotyping and Southern hybridization. PMID- 27193704 TI - Advanced lymphoblastic clones detection in T-cell leukemia. AB - T cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignant neoplasm of the lymphocyte precursors that suffered malignant transformation arresting the lymphoid cell differentiation. Clinical studies revealed monoor, more rarely, oligoclonal nature of the disease. A precise identification of malignant clone markers is both the crucial stage of early diagnostics and the essential prognostic factor for therapeutic treatment. Here we present an improved system for unbiased detection of lymphoblastic clones in bone marrow aspirates of T-ALL patients. The system based on multiplex PCR of rearranged T-cell receptor locus (TRB) and straightforward sequencing of the resulted PCR fragments. Testing of the system on genomic DNA from Jurkat cell line and four clinical bone marrow aspirates revealed a set of unique TRB rearrangements that precisely characterize each of tested samples. Therefore, the outcome of the system produces highly informative molecular genetic markers for further monitoring of minimal residual disease in T-ALL patients. PMID- 27193706 TI - Antitumor effect of arabinogalactan and platinum complex. AB - The article presents the results of investigation of antitumor properties of platinum-arabinogalactan complex. We showed the ability of the complex to inhibit the growth of Ehrlich ascites tumor cells. It is found that the distribution of the platinum-arabinogalactan complex is not specific only for tumor cells in mice. The complex was found in all tissues and organs examined (ascites cells, embryonic cells, kidney, and liver). The mechanism of action of the arabinogalactan-platinum complex may be similar to cisplatin as the complex is able to accumulate in tumor cells. PMID- 27193707 TI - The functional activity of hypothalamic signaling systems in rats with neonatal diabetes mellitus treated with metformin. AB - The effect of the two-month metformin treatment (200 mg/kg/day) of rats with the neonatal model of type 2 diabetes mellitus on the functional activity of hypothalamic signaling systems was studied. It was shown that metformin treatment restored the sensitivity of hypothalamic adenylyl cyclase signaling system to agonists of the type 4 melanocortin receptor and the type 2 dopamine receptor but did not influence significantly the functions of the insulin signaling system. These data suggest new targets and mechanisms of metformin action in the CNS, which may mediate its restoring effect on energy homeostasis impaired in diabetic pathology. PMID- 27193708 TI - Change in the selection of microRNA strands during DNA damage induction. AB - It was first shown that DNA damage induction in mitomycin C-treated HeLa cells leads to a change in the selection of 5p and 3p microRNA duplex strands in the formation of the RNA-induced silencing complex (RISC). PMID- 27193702 TI - The Roles of the Olivocerebellar Pathway in Motor Learning and Motor Control. A Consensus Paper. AB - For many decades, the predominant view in the cerebellar field has been that the olivocerebellar system's primary function is to induce plasticity in the cerebellar cortex, specifically, at the parallel fiber-Purkinje cell synapse. However, it has also long been proposed that the olivocerebellar system participates directly in motor control by helping to shape ongoing motor commands being issued by the cerebellum. Evidence consistent with both hypotheses exists; however, they are often investigated as mutually exclusive alternatives. In contrast, here, we take the perspective that the olivocerebellar system can contribute to both the motor learning and motor control functions of the cerebellum and might also play a role in development. We then consider the potential problems and benefits of it having multiple functions. Moreover, we discuss how its distinctive characteristics (e.g., low firing rates, synchronization, and variable complex spike waveforms) make it more or less suitable for one or the other of these functions, and why having multiple functions makes sense from an evolutionary perspective. We did not attempt to reach a consensus on the specific role(s) the olivocerebellar system plays in different types of movements, as that will ultimately be determined experimentally; however, collectively, the various contributions highlight the flexibility of the olivocerebellar system, and thereby suggest that it has the potential to act in both the motor learning and motor control functions of the cerebellum. PMID- 27193709 TI - The inhibitors of Arp2/3 complex and WASP proteins modulate the effect of glutoxim on Na(+) transport in frog skin. AB - Using voltage-clamp technique, the involvement of WASP proteins and Arp2/3 complex in the effect of immunomodulator drug glutoxim on Na(+) transport in frog skin was investigated. It was shown for the first time that preincubation of the skin with the N-WASP inhibitor wiskostatin or the Arp2/3 complex inhibitor CK 0944666 significantly decreases the stimulatory effect of glutoxim on Na(+) transport. The data suggest the involvement of actin filament polymerization and branching in the glutoxim effect on Na(+) transport in frog skin. PMID- 27193710 TI - Temperature dependence of protein fluorescence in Rb. sphaeroides reaction centers frozen to 80 K in the dark or on the actinic light as the indicator of protein conformational dynamics. AB - The differences in the average fluorescence lifetime (tauav) of tryptophanyls in photosynthetic reaction center (RC) of the purple bacteria Rb. sphaeroides frozen to 80 K in the dark or on the actinic light was found. This difference disappeared during subsequent heating at the temperatures above 250 K. The computer-based calculation of vibration spectra of the tryptophan molecule was performed. As a result, the normal vibrational modes associated with deformational vibrations of the aromatic ring of the tryptophan molecule were found. These deformational vibrations may be active during the nonradiative transition of the molecule from the excited to the ground state. We assume that the differences in tauav may be associated with the change in the activity of these vibration modes due to local variations in the microenvironment of tryptophanyls during the light activation. PMID- 27193711 TI - Peroxiredoxin 6 is a natural radioprotector. AB - After injection of 20 mg/kg peroxiredoxin 6 to male Kv:SHK mice 15 min before X ray irradiation in the range of lethal doses (7-10 Gy), the mice remained alive for 30 days, whereas the mortality of the control animals was 100%. In the irradiated animals, peroxiredoxin 6 decreased the severity of radiation-induced leucopenia, granulocytopenia, and thrombocytopenia, increased the number of blood corpuscles, and prevented the mass death of epithelial cells and the destruction of the small intestine. Thus, peroxiredoxin 6 can be regarded as a prophylactic radioprotective agent. PMID- 27193712 TI - EPR spectroscopy solutions for assessment of decellularization of intrathoracic organs and tissues. AB - Using EPR spectroscopy it was established that the determination of the concentration of paramagnetic centers in lyophilized tissues allows indirect evaluation of the quality of decellularization of intrathoracic organs (diaphragm, heart, and lungs), since the content of paramagnetic particles in them can serve as a criterion of cell viability and points to the necessity to repeat decellularization. Experiments in rats showed that the EPR spectra of the native thoracic organs contained paramagnetic centers with g-factor values ranging from 2.007 to 2.011 at a concentration of 10(-8) to 6.62 * 10(-7) mol/g of lyophilized tissue, whereas in all decellularized tissues of the same organs paramagnetic particles were not detected. PMID- 27193714 TI - Transcription factor Oct-1 stimulates the release of Mts1/S100A4 protein by the cancer cells. AB - The effect of the transcription factor Oct-1 (POU2F1) on the expression of the tumor cell marker metastasin (Mts1/S100A4) was studied. Comparative analysis of various tumor lines showed no clear correlation between the expression level of Mts1/S100A4 and the content of Oct-1. However, at stable transfection of tumor cells with Oct-1A, Oct-1L, and Oct-1X isoforms we detected an elevated level of Oct-1, which stimulated Mts1/S100A4 secretion. These findings extend our understanding of the molecular mechanisms of the tumorigenic effect of Oct-1. PMID- 27193713 TI - New monoclonal antibodies to the Ebola virus glycoprotein: Identification and analysis of the amino acid sequence of the variable domains. AB - We determined the nucleotide and amino acid sequences of variable domains of three new monoclonal antibodies to the glycoprotein of Ebola virus capsid. The framework and hypervariable regions of immunoglobulin heavy and light chains were identified. The primary structures were confirmed using massspectrometry analysis. Immunoglobulin database search showed the uniqueness of the sequences obtained. PMID- 27193715 TI - Pleiotropic effect of thyroid hormones on gene expression in fish as exemplified from the blue bream Ballerus ballerus (Cyprinidae): Results of transcriptomic analysis. AB - A pronounced pleiotropic effect of thyroid hormones on the regulation of gene expression in fish in postembryogenesis was demonstrated for the first time using larvae and juveniles of the blue bream Ballerus ballerus as an example. Genome wide transcriptome sequencing (RNA-seq) identified 1212 differentially expressed genes in the brain and liver of fish kept in triiodothyronine solution (0.25 ng/mL). Our data show that the regulation of gene expression by thyroid hormones is widespread in nature: it involves not only the structural genes but also the regulatory genes. A significant number of genes under the control of thyroid hormones are involved in the determination of morphological traits. PMID- 27193716 TI - The oxidative modification of cellular fibrin-stabilizing factor. AB - For the first time, the induced oxidative modification of cellular fibrin stabilizing factor (cFXIII) has been studied. According to the electrophoresis analysis, the conversion of oxidized cFXIII into FXIIIa resulted in producing the enzyme that significantly lost the initial enzymatic activity. At the same time, FXIIIa subjected to induced oxidation was completely devoid of enzymatic activity. The results of FTIR spectroscopy showed that the oxidation of cFXIII or FXIIIa was accompanied by profound changes both in chemical and spatial structures of the protein. The results of this study are in good agreement with our earlier assumption regarding the antioxidant role of the regulatory subunits B of plasma fibrin-stabilizing factor. PMID- 27193717 TI - Mechanism of caspase-2 activation upon DNA damage. AB - The mechanism of caspase-2 activation in response to DNA damage was studied using human ovarian cancer cells Caov-4 treated with chemotherapeutic agent cisplatin. It was shown that mutations of the three cleavage sites of caspase-2 do not affect the assembly of the macromolecular complex of caspase-2 and its activation, but, conversely, stabilize this complex, most likely, via the inhibition of the dissociation of the active caspase-2. PMID- 27193718 TI - Impact of tightly focused femtosecond laser pulses on nucleolus-like bodies of mouse GV oocyte and the ability of mouse oocytes to mature. AB - Using femtosecond laser radiation, nucleolus-like bodies (NLBs) of mouse oocytes were locally dissected without damage to zona pellucida, cytoplasmic membrane, nuclear membrane, and nucleoplasm surrounding NLB. It was found that, after dissection of 2.7 * 10(-11) cm(3) of NLB material, which is approximately 5.2% of 10 MUm NLB volume, the probability of germinal vesicle oocyte development to metaphase II stage of meiosis decreased 3-7 times compared to the non-treated oocytes. This result indicates that NLB material organization is significant for mouse oocyte maturation. PMID- 27193720 TI - Transcriptional control of insulin-sensitive glucose carrier Glut4 expression in adipose tissue cells. AB - In search for new targets for obesity treatment, we have studied the effect of several transcription factors on the conversion of murine preadipocytes from the 3T3-L1 cell line into adipocytes. We have found that knockdown of Prep1 gene expression affects adipogenic differentiation and results in significant increase in the insulin-sensitive glucose carrier Glut4 gene expression. PMID- 27193719 TI - Investigation of the effect of alpha-melanocyte-stimulating hormone on proliferation and early stages of differentiation of human induced pluripotent stem cells. AB - We have studied the influence of alpha-melanocyte-stimulating hormone (alpha-MSH) on proliferation and early stages of differentiation of human induced pluripotent stem cells (iPSc). We have demonstrated that alpha-MSH receptor genes are expressed in undifferentiated iPSc. The expression levels of MCR1, MCR2, and MCR3 increased at the embryoid body (EB) formation stage. The formation of neural progenitors was accompanied by elevation of MCR2, MCR3, and MCR4 expression. alpha-MSH had no effect on EB generation and iPSc proliferation at concentrations ranging from 1 nM to 10 MUM. At the same time, alpha-MSH increased the generation of neural rosettes in human iPSc cultures more than twice. PMID- 27193721 TI - Hypoxia as pathogenic factor affecting the eye tissues: The selective apoptotic damage of the conjunctiva and anterior epithelium of the cornea. AB - The effect of acute hypoxia on the occurrence of apoptosis in eye cells in rats placed in a pressure chamber was studied. Selective primary lesion of cells of the conjunctiva and the anterior corneal epithelium was found. A possible role of the simulated hypoxic conditions in the dry eye syndrome pathogenesis, which is accompanied by primary lesion of cells in the anterior eye surface tissues is discussed. PMID- 27193722 TI - Secretory activity of the brain and peripheral organs: Spontaneous and stimulated release of noradrenaline in the ontogenesis of rats. AB - Spontaneous and K(+)-stimulated release of noradrenaline from the hypothalamus, adrenal gland, and organ of Zuckerkandl under their flowing incubation was investigated in the perinatal period of ontogenesis of rats. The results suggest that, during the investigated period of ontogenesis, adrenal glands are the main source of noradrenaline in the blood, whereas the contributions of the organ of Zuckerkandl and the brain are not as significant and change during this period. PMID- 27193724 TI - The level of the Phf10 protein, a PBAF chromatin-remodeling complex subunit, correlates with the Mts1/S100A4 expression in human cancer cell lines. AB - Mts1 (S100A4) protein is a marker of metastatic tumor cells, which is associated with a poor diagnostic prognosis for cancer progression. Therefore, it is important to study the S100A4 gene expression. According to our preliminary data, PHF10, a PBAF remodeling complex component, can play an important role in the transcription regulation of the S100A4 gene. We studied the expression of S100A4 and the total PHF10 protein in some cell lines. We have found that, in the cell lines studied, the PHF10 expression is correlated with the S100A4 expression. PMID- 27193723 TI - Expression and purification of an engineered human endothelin receptor B in a monomeric form. AB - In humans, two endothelin receptors, ETa and ETb, are activated by three endogenous 21-mer cyclic peptides, ET-1, ET-2, and ET-3, which control various physiological processes, including vasoconstriction, vasodilation, and stimulation of cell proliferation. The first stage of this study it to produce a stable solubilized and purified receptor in a monodisperse state. This article is focused on the engineering, expression, purification, and characterization of the endothelin receptor B for subsequent structural and functional studies. PMID- 27193725 TI - Elaboration of the Gothenburg model of person-centred care. AB - BACKGROUND: Person-centred care (PCC) is increasingly advocated as a new way of delivering health care, but there is little evidence that it is widely practised. The University of Gothenburg Centre for Person-Centred Care (GPCC) was set up in 2010 to develop and implement person-centred care in clinical practice on the basis of three routines. These routines are based on eliciting the patient's narrative to initiate a partnership; working the partnership to achieve commonly agreed goals; and using documentation to safeguard the partnership and record the person's narrative and shared goals. OBJECTIVE: In this paper, we aimed to explore professionals' understanding of PCC routines as they implement the GPCC model in a range of different settings. METHODS: We conducted a qualitative study and interviewed 18 clinician-researchers from five health-care professions who were working in seven diverse GPCC projects. RESULTS: Interviewees' accounts of PCC emphasized the ways in which persons are seen as different from patients; the variable emphasis placed on the person's goals; and the role of the person's own resources in building partnerships. CONCLUSION: This study illustrates what is needed for health-care professionals to implement PCC in everyday practice: the recognition of the person is as important as the specific practical routines. Interviewees described the need to change the clinical mindset and to develop the ways of integrating people's narratives with clinical practice. PMID- 27193726 TI - Novel psychoactive benzofurans strongly increase extracellular serotonin level in mouse corpus striatum. AB - We examined the effects of three benzofurans [1-(Benzofuran-5-yl)-N-methylpropan 2-amine (5-MAPB), 1-(Benzofuran-2-yl)-N-methylpropan-2-amine (2-MAPB), and 1 (Benzofuran-5-yl)-N-ethylpropan-2-amine (5-EAPB)] on the extracellular monoamine level in mouse corpus striatum by the microdialysis method and compared them with the effects of psychoactive 3,4-Methylenedioxymethamphetamine (MDMA). The effects of benzofurans on the extracellular monoamine level were qualitatively analogous to that of MDMA, with an increase in serotonin (5-HT) level exceeding dopamine (DA) level. The effects of 2-MAPB and 5-EAPB were almost the same as the effect of MDMA. However, 5-MAPB strongly increased extracellular monoamine level than MDMA. These differences in the potency appear to have a structure-activity relationship. The administration of 5-MAPB (1.6 * 10(-4) mol/kg B.W.) resulted in the death of two-thirds of the mice. The same dose of MDMA did not cause any deaths. The administration of 5-MAPB (1.6 * 10(-4) mol/kg B.W.) produced a 3.41 degrees C +/- 0.28 degrees C rise in rectal temperature after 1 hr, whereas the administration of MDMA (1.6 * 10(-4) mol/kg B.W.) produced an approximate 1.85 degrees C +/- 0.26 degrees C rise. These results suggest that benzofurans have 5 HT toxicity similar to MDMA, and 5-MAPB has a higher risk of lethal intoxication than MDMA. Furthermore, 5-APB, the metabolic product of 5-MAPB demethylation, may be involved in the acute 5-HT toxicity and may cause lethal intoxication in mice. PMID- 27193727 TI - Fenofibrate reduces cisplatin-induced apoptosis of renal proximal tubular cells via inhibition of JNK and p38 pathways. AB - Cisplatin is widely used as a standard chemotherapy for solid tumors. The major adverse effect of cisplatin is nephrotoxicity in proximal tubular cells, via oxidative stress, DNA damage, cell apoptosis, and inflammation. The aim of this study was to investigate the pharmacological effect and mechanism of fibrate drugs on cisplatin-induced renal proximal tubular cell death. Cisplatin decreased cell viability of LLC-PK1 and HK-2 cells in a dose-dependent manner. Cisplatin induced apoptosis was attenuated by co-treatment with fenofibrate while less so with clofibrate and bezafibrate. Fenofibrate's protective effect was not complimented by co-treatment with GW6471, a PPARalpha antagonist, indicating the protective effect occurred via a PPARalpha-independent mechanism. Treating cells with cisplatin induced reactive oxygen species (ROS), c-JUN N-terminal kinase (JNK), and p38 kinase (p38), but not extracellular signal-regulated kinase (ERK). Fenofibrate reversed cisplatin-induced JNK and p38 activation, but had no effect on ROS production. The findings suggest fenofibrate's protective effect on cisplatin-induced cytotoxicity is mediated by inhibition of JNK and p38. Moreover, fenofibrate did not alter cisplatin's antitumor effect on cancer cell lines including T84, SW-480, HepG2, and SK-LU-1 cells. Therefore, fenofibrate may be a candidate agent for further development as an adjuvant to cisplatin treatment. PMID- 27193728 TI - Effects of PAMAM dendrimers with various surface functional groups and multiple generations on cytotoxicity and neuronal differentiation using human neural progenitor cells. AB - Polyamidoamine (PAMAM) dendrimers have potential for biological applications as delivery systems for genes, drugs, and imaging agents into the brain, but their developmental neurotoxicity remains unknown. We investigated the effects of PAMAM dendrimers with various surface functional groups and multiple generations on neuronal differentiation using human neural progenitor cells at an equal mass concentration. Only PAMAM dendrimers containing amine (NH2) surface groups at concentrations of 10 MUg/mL significantly reduced cell viability and neuronal differentiation, compared with non-amine-terminated dendrimers. PAMAM-NH2 with generation (G)3, G4, G5 G6, and G7 significantly decreased cell viability and inhibited neuronal differentiation from a concentration of 5 MUg/mL, but G0, G1, and G2 dendrimers did not have any effect at this concentration. Cytotoxicity indices of PAMAM-NH2 dendrimers at 10 MUg/mL correlated well with the zeta potentials of the particles. Surface group density and particle number in unit volume is more important characteristic than particle size to influence cytotoxicity for positive changed dendrimers. PAMAM-50% C12 at 1 MUg/mL altered the expression level of the oxidative stress-related genes, ROR1, CYP26A1, and TGFB1, which is a DNA damage response gene. Our results indicate that PAMAM dendrimer exposure may have a surface charge-dependent adverse effect on neuronal differentiation, and that the effect may be associated with oxidative stress and DNA damage during development of neural cells. PMID- 27193729 TI - Potential protective effect of arginine against 4-nitrophenol-induced ovarian damage in rats. AB - 4-nitrophenol (PNP) is generally regarded as a diesel exhaust particle (DEP). Arginine plays an important role as a new feed additive, possessing highly efficient antioxidant activities. Here we investigated the effects of dietary supplementation with arginine against ovarian damage induced by PNP in rats. A total of thirty-two female rats postnatal day 28 (PND 28) were randomly divided into four groups. Two groups were fed with basal diet or 13 g/kg arginine in diet for 4 weeks, respectively; the other two groups were given PNP (100 mg/kg b.w.) daily by subcutaneous injection for 2 weeks following pretreatment with either basal diet or arginine diet for 2 weeks. The values of body weight gain (BWG), average daily gain (ADG) and percentage weight gain (PWG) upon PNP treatment were significantly reduced than those in other groups. The relative liver weight in the PNP group was significantly decreased compared with the control group. Treatment with PNP significant reduced the number of corpora lutea, although serum 17beta-estradiol (E2) and progesterone (P4) concentrations were unchanged. The morphology of the ovaries in PNP-treated rats displayed necrosis, follicular deformation and granulosa cells irregular arrangement. Moreover, exposure to PNP enhanced production of malondialdehyde (MDA) and hydrogen peroxide (H2O2), and decreased the activities of total superoxide dismutase (T-SOD) and catalase (CAT), and the co-administration of arginine can attenuate the oxidative stress caused by PNP. These results suggest that arginine may have a protective effect against ovarian damage induced by PNP owing to its antioxidant capacity effect. PMID- 27193730 TI - Simpler alternative to CARCINOscreen((r)) based on quantitative PCR (qPCR). AB - Carcinogenicity of chemicals in our environment is one of the most important health hazards to humans. Recently, a microarray-based short-term prediction system for the hepatocarcinogenicity of chemicals, named CARCINOscreen((r)), was developed. Although the system is a promising tool reported to have an ability to predict hepatocarcinogenicity in rats with 92.9% accuracy, it requires specialized equipment and skilled bioinformatics approaches for data analysis. Therefore, we attempted to develop a quantitative PCR (qPCR)-based system as an alternative to microarray-based CARCINOscreen((r)). Finally, an optimized gene set consisting of four predictive genes (Abcb1b, Eprs, Map3K8, and Igh-6) was selected from among 3,150 combinations of candidate gene sets. The results of training- and validation-phase trials showed that the qPCR-based alternative to the microarray-based CARCINOscreen((r)) could predict the hepatocarcinogenicity of chemicals in rats with 82.8%-86.4% accuracy. One of the predictive genes, Abcb1b, a member of the ATP-binding cassette protein superfamily and multi-drug resistance-associated protein, and the results of this study may indicate a close relation of this gene to the carcinogenicity of chemicals. The prediction performance of the qPCR-based CARCINOscreen((r)), as well as its user friendliness and cost efficiency, suggests that this method is promising for application to primary health hazard assessment. Thus, the qPCR-based CARCINOscreen((r)) is considered as a promising tool for predicting the carcinogenicity of chemicals. PMID- 27193731 TI - Short-term manganese inhalation decreases brain dopamine transporter levels without disrupting motor skills in rats. AB - Manganese (Mn) is used in industrial metal alloys and can be released into the atmosphere during methylcyclopentadienyl manganese tricarbonyl combustion. Increased Mn deposition in the brain after long-term exposure to the metal by inhalation is associated with altered dopamine metabolism and neurobehavioral problems, including impaired motor skills. However, neurotoxic effects of short term exposure to inhaled Mn are not completely characterized. The purpose of this study is to define the neurobehavioral and neurochemical effects of short-term inhalation exposure to Mn at a high concentration using rats. Male Sprague-Dawley rats were exposed to MnCl2 aerosol in a nose-only inhalation chamber for 3 weeks (1.2 um, 39 mg/m(3)). Motor coordination was tested on the day after the last exposure using a rotarod device at a fixed speed of 10 rpm for 2 min. Also, dopamine transporter and dopamine receptor protein expression levels in the striatum region of the brain were determined by Western blot analysis. At a rotarod speed of 10 rpm, there were no significant differences in the time on the bar before the first fall or the number of falls during the two-minute test observed in the exposed rats, as compared with controls. The Mn-exposed group had significantly higher Mn levels in the lung, blood, olfactory bulb, prefrontal cortex, striatum, and cerebellum compared with the control group. A Mn concentration gradient was observed from the olfactory bulb to the striatum, supporting the idea that Mn is transported via the olfactory pathway. Our results demonstrated that inhalation exposure to 39 mg/m(3) Mn for 3 weeks induced mild lung injury and modulation of dopamine transporter expression in the brain, without altering motor activity. PMID- 27193732 TI - Ochratoxin A mediates MAPK activation, modulates IL-2 and TNF-alpha mRNA expression and induces apoptosis by mitochondria-dependent and mitochondria independent pathways in human H9 T cells. AB - Ochratoxin A (OTA) is a natural fungal secondary metabolite that contaminates food and animal feed. Human exposure and involvement of this mycotoxin in several pathologies have been demonstrated worldwide. We investigated OTA immunotoxicity on H9 cells, a human cutaneous CD4+ T lymphoma cell line. Cells were treated with 0, 1, 5, 10, and 20 uM OTA for up to 24 hr. Western blotting revealed increased phosphorylation of all three major mitogen-activated protein kinases (extracellular signal-regulated kinase, c-Jun amino-terminal kinase, p38). OTA triggered mitochondrial transmembrane potential loss and caspase-3 activation. The 24-hr OTA treatment caused marked changes in cell morphology and DNA fragmentation, suggesting the occurrence of apoptotic events that involved a mitochondria-dependent pathway. Moreover, OTA triggered significant modulation of survivin, interleukin 2 (IL-2) and tumor necrosis factor alpha (TNF-alpha): mRNA expression of survivin and IL-2 were decreased, while TNF-alpha was increased. OTA also caused caspase-8 activation in a time-dependent manner, which evokes the death receptor pathway activation; we suspect that this occurred via the autocrine pro-apoptotic effect of TNF-alpha on H9 cells. PMID- 27193734 TI - Beauvericin-induced cell apoptosis through the mitogen-activated protein kinase pathway in human nonsmall cell lung cancer A549 cells. AB - Beauvericin (BEA) is a cyclic hexadepsipeptide that derives from Codyceps cicadae. Our previous study results indicated that the cytotoxic effects of BEA on human A549 lung cancer cells BEA occur through an apoptotic pathway, which involves the up-regulation of cytochrome c release from mitochondria, upregulation of caspase 3 activity, and cellular and morphological changes. In this study, we identified that the mitogen-activated protein kinase (MAPK) inhibitor U0126 inhibits the cytotoxic effects of BEA on A549 cells. After exposing human A549 cells to 10 MUM BEA, we observed a significant and dose dependent increase in the percentage of hypoploid (sub-G1) phase cells in the A549 population. Following the pretreatment of the A549 cells with 25 MUM U0126, the distribution of A549 cells in the sub-G1 phase decreased significantly. The BEA treatment resulted in a significant increase apoptosis in A549 cells by in situ terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Moreover, the MEK1/2 (mitogen-activated protein kinase kinase)-ERK42/44 (extracellular signal-regulated kinases)-90RSK (ribosomal s6 kinase) signaling pathway was activated in BEA-induced apoptotic A549 cells. Furthermore, treatment with MEK1/2 inhibitor U0126 was capable to attenuate the BEA induced typical apoptotic morphological change, apoptotic cells, and MEK1/2-ERK42/44-90RSK signaling pathway. These results suggested that MEK1/2-ERK42/44-90RSK signaling pathway may play a important role in BEA-induced apoptosis in human NSCLC A549 cancer cells. PMID- 27193733 TI - Platycodin D exerts anti-tumor efficacy in H22 tumor-bearing mice via improving immune function and inducing apoptosis. AB - Platycodin D (PD), a major saponin derived and isolated from the roots of Platycodon grandiflorum, exerts potent growth inhibition and strong cytotoxicity against various cancer cell lines. However, the anti-tumor efficacy of PD on H22 hepatocellular carcinoma remains unknown. In the present study, we aimed to explore the anti-hepatoma activity in vivo and the underlying mechanism of PD in H22 tumor-bearing mice. The results revealed that PD could considerably suppress tumor growth with no significant side effects on immune organs and body weight. Further investigations showed that the levels of serum cytokines, including interferon gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-2 (IL-2), were enhanced by PD administration. On the other hand, PD inhibited the production of vascular endothelial growth factor (VEGF) in serum of H22 tumor mice. Additionally, the observations from H&E and Hoechst 33258 staining results demonstrated that PD noticeably induced apoptosis in H22 hepatocellular carcinoma cells. Importantly, immunohistochemical analysis showed that PD treatment increased Bax expression and decreased Bcl-2 and VEGF expression of H22 tumor tissues in a dose-dependent manner. Taken together, the findings in the present investigation clearly demonstrated that the PD markedly suppressed the tumor growth of H22 transplanted tumor in vivo at least partly via improving the immune functions, inducing apoptosis, and inhibiting angiogenesis. PMID- 27193735 TI - Electropharmacological effects of amantadine on cardiovascular system assessed with J-Tpeak and Tpeak-Tend analysis in the halothane-anesthetized beagle dogs. AB - Since amantadine-induced long QT syndrome has been clinically reported, we investigated its electropharmacological effects to estimate the extent of proarrhythmic risk by using the halothane-anesthetized beagle dogs (n = 4). Amantadine in doses of 0.1, 1 and 10 mg/kg was infused over 10 min with a pause of 20 min under the monitoring of multiple cardiovascular variables. J-Tpeak and Tpeak-Tend were separately measured on the lead II electrocardiogram to precisely analyze the net balance between inward and outward current modifications by amantadine. The low dose increased the ventricular contractile force, but suppressed the intraventricular conduction. The middle dose prolonged the QT interval besides enhancing the changes induced by the low dose. The high dose increased the mean blood pressure, left ventricular end-diastolic pressure and total peripheral resistance, and accelerated the atrioventricular nodal conduction, but decreased the cardiac output besides enhancing the changes induced by the middle dose. A reverse use-dependence was confirmed in the repolarization delay. Amantadine hardly affected the J-Tpeak, but prolonged the Tpeak-Tend. Amantadine can be considered to stimulate Ca(2+) channel but inhibit Na(+) and K(+) channels in the in situ heart. J-Tpeak and Tpeak-Tend analysis suggests that amantadine may possess modest risk for arrhythmia. PMID- 27193736 TI - Child dietary and eating behavior outcomes up to 3.5 years after an early feeding intervention: The NOURISH RCT. AB - OBJECTIVE: To evaluate dietary intake impact outcomes up to 3.5 years after the NOURISH early feeding intervention (concealed allocation, assessor masked randomized controlled trial). METHODS: In this study, 698 first-time mothers with healthy term infants were allocated to receive anticipatory guidance on protective feeding practices or usual care. Outcomes were assessed at 2, 3.7, and 5 years (3.5 years post-intervention). Dietary intake was assessed by 24-h recall and Child Dietary Questionnaire. Mothers completed a food preference questionnaire and Children's Eating Behavior Questionnaire. Linear mixed models assessed group, time, and time * group effects. RESULTS: There were no group or time * group effects for fruit, vegetable, discretionary food, and nonmilk sweetened beverage intake. Intervention children showed a higher preference for fruit (74.6% vs. 69.0% liked, P < 0.001), higher Child Dietary Questionnaire score for fruit and vegetables (15.3 vs. 14.5, target >=18, P = 0.03), lower food responsiveness (2.3 vs. 2.4, of maximum 5, P = 0.04), and higher satiety responsiveness (3.1 vs. 3.0, of maximum 5, P = 0.04). CONCLUSIONS: Compared with usual care, an early feeding intervention providing anticipatory guidance regarding positive feeding practices led to small improvements in child dietary score, food preferences, and eating behaviors up to 5 years of age, but not in dietary intake measured by 24-h recall. PMID- 27193739 TI - Partially oxidized iridium clusters within dendrimers: size-controlled synthesis and selective hydrogenation of 2-nitrobenzaldehyde. AB - Iridium clusters nominally composed of 15, 30 or 60 atoms were size-selectively synthesized within OH-terminated poly(amidoamine) dendrimers of generation 6. Spectroscopic characterization revealed that the Ir clusters were partially oxidized. All the Ir clusters efficiently converted 2-nitrobenzaldehyde to anthranil and 2-aminobenzaldehyde under atmospheric hydrogen at room temperature in toluene via selective hydrogenation of the NO2 group. The selectivity toward 2 aminobenzaldehyde over anthranil was improved with the reduction of the cluster size. The improved selectivity is ascribed to more efficient reduction than intramolecular heterocyclization of a hydroxylamine intermediate on smaller clusters that have a higher Ir(0)-phase population on the surface. PMID- 27193737 TI - Randomized-controlled trial of mindfulness-based cancer recovery versus supportive expressive group therapy among distressed breast cancer survivors (MINDSET): long-term follow-up results. AB - BACKGROUND: Mindfulness-based cancer recovery (MBCR) and supportive expressive group therapy (SET) are two well-validated psychosocial interventions, but they have not been directly compared, and little is known about long-term outcomes. This comparative effectiveness study measured the effects of these two interventions immediately following the groups and for 1 year thereafter in distressed breast cancer survivors. METHODS: Two hundred fifty-two distressed Stage I-III breast cancer survivors were randomized into either MBCR or SET. Women completed questionnaires addressing mood, stress symptoms, quality of life, social support, spirituality and post-traumatic growth before and after the interventions, and 6 and 12 months later. RESULTS: Immediately following the intervention, women in MBCR reported greater reduction in mood disturbance (primarily fatigue, anxiety and confusion) and stress symptoms including tension, sympathetic arousal and cognitive symptoms than those in SET. They also reported increased emotional and functional quality of life, emotional, affective and positive social support, spirituality (feelings of peace and meaning in life) and post-traumatic growth (appreciation for life and ability to see new possibilities) relative to those in SET, who also improved to a lesser degree on many outcomes. Effect sizes of the time * group interactions were small to medium, and most benefits were maintained over 12 months of follow-up. CONCLUSIONS: This study is the first and largest to demonstrate sustained benefits of MBCR in distressed breast cancer survivors relative to an active control. MBCR was superior to SET for improving psychological well-being with lasting benefits over 1 year, suggesting these women gained long-lasting and efficacious tools to cope with cancer. TRIAL REGISTRATION: Registered on clinicaltrials.gov number NCT00390169, October 2006. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27193738 TI - Truncations of xyloglucan xylosyltransferase 2 provide insights into the roles of the N- and C-terminus. AB - Xyloglucan is the most abundant hemicellulose in the primary cell wall of dicotyledonous plants. In Arabidopsis, three xyloglucan xylosyltransferases, XXT1, XXT2, and XXT5, participate in xylosylation of the xyloglucan backbone. Despite the importance of these enzymes, there is a lack of information on their structure and the critical residues required for substrate binding and transferase activity. In this study, the roles of different domains of XX2 in protein expression and catalytic activity were investigated by constructing a series of N- and C-terminal truncations. XXT2 with an N-terminal truncation of 31 amino acids after the predicted transmembrane domain showed the highest protein expression, but truncations of more than 31 residues decreased protein expression and catalytic activity. XXT2 constructs with C-terminal truncations showed increased protein expression but decreased activity, particularly for truncations of 44 or more amino acids. Site-directed mutagenesis was also used to investigate six positively charged residues near the C-terminus and found that four of the mutants showed decreased enzymatic activity. We conclude that the N- and C termini of XXT2 have important roles in protein folding and enzymatic activity: the stem region (particularly the N-terminus of the catalytic domain) is critical for protein folding and the C-terminus is essential for enzymatic activity but not for protein folding. PMID- 27193741 TI - Microfluidic-based photocatalytic microreactor for environmental application: a review of fabrication substrates and techniques, and operating parameters. AB - Photochemical technology with microfluidics is emerging as a new platform in environmental science. Microfluidic technology has various advantages, like better mixing and a shorter diffusion distance for the reactants and products; and uniform distribution of light on the photocatalyst. Depending on the material type and related applications, several fabrication techniques have been adopted by various researchers. Microreactors have been prepared by various techniques, such as lithography, etching, mechanical microcutting technology, etc. Lithography can be classified into photolithography, soft lithography and X-ray lithography techniques whereas the etching process is divided into wet etching (chemical etching) and dry etching (plasma etching) techniques. Several substrates, like polymers, such as polydimethyl-siloxane (PDMS), polymethyle methacrylate (PMMA), hydrogel, etc.; metals, such as stainless steel, titanium foil, etc.; glass, such as silica capillary, glass slide, etc.; and ceramics have been used for microchannel fabrication. During degradation in a microreactor, the degradation efficiency is affected by few important parameters such as flow rate, initial concentration of the target compound, microreactor dimensions, light intensity, photocatalyst structure and catalyst support. The present paper discusses and critically reviews fabrication techniques and substrates used for microchannel fabrication and critical operating parameters for organics, especially dye degradation in the microreactor. The kinetics of degradation has also been discussed. PMID- 27193740 TI - Crisaborole Topical Ointment, 2% in Patients Ages 2 to 17 Years with Atopic Dermatitis: A Phase 1b, Open-Label, Maximal-Use Systemic Exposure Study. AB - BACKGROUND: Phosphodiesterase-4 (PDE4) is a promising target in atopic dermatitis (AD) treatment. The pharmacokinetics (PK), safety, and efficacy of crisaborole topical ointment, 2% (formerly AN2728) (Anacor Pharmaceuticals, Palo Alto, CA), a boron-based benzoxaborole PDE4 inhibitor, were evaluated in children with mild to moderate AD. METHODS: This phase 1b, open-label, maximal-use study of crisaborole topical ointment, 2% applied twice daily (dose 3 mg/cm(2) ) for 28 days enrolled patients ages 2 to 17 years with extensive AD involving 25% or more or 35% or more treatable body surface area, depending on age. Primary PK and safety assessments included systemic exposure to crisaborole and its metabolites after 7 days of treatment and the incidence of treatment-emergent adverse events (TEAEs). Secondary efficacy assessments included change from baseline in Investigator Static Global Assessment (ISGA), treatment success (ISGA score <=1 with a two grade or greater improvement from baseline), and improvement in five AD signs and symptoms. RESULTS: Of 34 patients enrolled, 31 completed the study. Crisaborole was rapidly absorbed, with limited systemic exposure between days 1 and 8. Twenty three of 34 patients reported one or more TEAEs; 95% were mild or moderate and one patient discontinued because of a TEAE. Mean ISGA scores declined from 2.65 at baseline to 1.15 at day 29, 47.1% of patients achieved treatment success, and 64.7% of patients achieved ISGA scores of clear (0) or almost clear . Mean severity scores for AD signs and symptoms declined throughout the study. CONCLUSIONS: This open-label study provides evidence that crisaborole topical ointment, 2% was well tolerated, with limited systemic exposure under maximal-use conditions in patients ages 2 years and older. PMID- 27193742 TI - Functional analysis of the N-terminal basic motif of a eukaryotic satellite RNA virus capsid protein in replication and packaging. AB - Efficient replication and assembly of virus particles are integral to the establishment of infection. In addition to the primary role of the capsid protein (CP) in encapsidating the RNA progeny, experimental evidence on positive sense single-stranded RNA viruses suggests that the CP also regulates RNA synthesis. Here, we demonstrate that replication of Satellite tobacco mosaic virus (STMV) is controlled by the cooperative interaction between STMV CP and the helper virus (HV) Tobacco mosaic virus (TMV) replicase. We identified that the STMV CP-HV replicase interaction requires a positively charged residue at the third position (3R) in the N-terminal 13 amino acid (aa) motif. Far-Northwestern blotting showed that STMV CP promotes binding between HV-replicase and STMV RNA. An STMV CP variant having an arginine to alanine substitution at position 3 in the N terminal 13aa motif abolished replicase-CP binding. The N-terminal 13aa motif of the CP bearing alanine substitutions for positively charged residues located at positions 5, 7, 10 and 11 are defective in packaging full-length STMV, but can package a truncated STMV RNA lacking the 3' terminal 150 nt region. These findings provide insights into the mechanism underlying the regulation of STMV replication and packaging. PMID- 27193743 TI - Validation of a Hindi version of the Epworth Sleepiness Scale (ESS) at AIIMS, New Delhi in sleep-disordered breathing. AB - PURPOSE: The Epworth Sleepiness Scale (ESS) is one of the most widely used questionnaire for the assessment of excessive daytime sleepiness (EDS) in sleep disordered breathing (SDB). This study was conducted to assess the validity of ESS in the Hindi language. METHODS: The Hindi version was developed by translation and back translation by independent translators. The English and Hindi versions were administered to 115 bilingual subjects who presented with symptoms of SDB, of whom 98 underwent a polysomnography at a tertiary care hospital in North India. RESULTS: The questionnaire had a high level of internal consistency as measured by Cronbach's alpha (alpha = 0.84). There was no significant difference between the mean ESS scores of Hindi and English versions (11.65 +/- 5.47 vs 11.70 +/- 5.49, respectively; p = 0.80). The Hindi version of ESS showed a strong correlation with the English version (Spearman's correlation rho = 0.98 and weighted kappa = 0.94). Each of the 8 individual questions of Hindi ESS demonstrated a good agreement with the corresponding English version. The Hindi ESS score was significantly higher in subjects with OSA compared to those without OSA (12.67 +/- 5.29 vs 7.76 +/- 5.44, respectively; p = 0.002). However, there was no difference in ESS score between mild and moderate OSA or between moderate and severe OSA. CONCLUSIONS: The Hindi version of the ESS showed a good internal consistency and a strong correlation with the English version and can be used in the Hindi-speaking population. PMID- 27193744 TI - The benefit of HH during the CPAP titration in the cool sleeping environment. AB - PURPOSE: Upper airway symptom associated with continuous positive airway pressure (CPAP) treatment is an important factor influencing CPAP adherence. There are conflicting data on the effect of a heated humidifier (HH) during CPAP titration for patients with obstructive sleep apnea hypopnea syndrome (OSAHS). This study investigated the effects of HH during CPAP titration in the cool sleeping environment. METHODS: Forty newly diagnosed OSAHS patients who received CPAP titration in the cool sleeping environment were randomly assigned to HH and non HH groups. A questionnaire was used to evaluate upper airway symptoms, satisfaction with initial CPAP treatment, and willingness to further use CPAP. Some therapy parameters including leak, apnea hypopnea index (AHI) reduction, and optimal CPAP pressure level were analyzed. We compared these subjective and objective data between the two groups. RESULTS: In subjective sensation, the use of HH can alleviate upper airway symptoms associated with CPAP titration (P < 0.001). The HH group has benefit in satisfaction with initial CPAP treatment (P < 0.001) and further willingness to use CPAP (P < 0.01), although there were no significant differences in leak, AHI reduction, and optimal CPAP pressure between the two groups. CONCLUSIONS: The use of HH is recommended during CPAP titration in the cool sleeping environment because of its benefit in the treatment of upper airway symptoms associated with CPAP therapy and improvement of the CPAP acceptance. PMID- 27193745 TI - Cost-effectiveness of Injectable Preexposure Prophylaxis for HIV Prevention in South Africa. AB - BACKGROUND: Long-acting injectable antiretrovirals such as rilpivirine (RPV) could promote adherence to preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) prevention. However, the cost-effectiveness of injectable PrEP is unclear. METHODS: We constructed a dynamic model of the heterosexual HIV epidemic in KwaZulu-Natal, South Africa, and analyzed scenarios of RPV PrEP scale-up for combination HIV prevention in comparison with a reference scenario without PrEP. We estimated new HIV infections, life-years and costs, and incremental cost-effectiveness ratios (ICERs), over 10-year and lifetime horizons, assuming a societal perspective. RESULTS: Compared with no PrEP, unprioritized scale-up of RVP PrEP covering 2.5%-15% of adults prevented up to 9% of new infections over 10 years. HIV prevention doubled (17%) when the same coverage was prioritized to 20- to 29-year-old women, costing $10 880-$19 213 per infection prevented. Prioritization of PrEP to 80% of individuals at highest behavioral risk achieved comparable prevention (4%-8%) at <1% overall coverage, costing $298-$1242 per infection prevented. Over lifetime, PrEP scale-up among 20 to 29-year-old women was very cost-effective (<$1600 per life-year gained), dominating unprioritized PrEP, while risk prioritization was cost-saving. PrEP's 10-year impact decreased by almost 50% with increases in ICERs (up to 4.2-fold) in conservative base-case analysis. Sensitivity analysis identified PrEP's costs, efficacy, and reliability of delivery as the principal drivers of uncertainty in PrEP's cost-effectiveness, and PrEP remained cost-effective under the assumption of universal access to second-line antiretroviral therapy. CONCLUSIONS: Compared with no PrEP, prioritized scale-up of RPV PrEP in KwaZulu-Natal could be very cost-effective or cost-saving, but suboptimal PrEP would erode benefits and increase costs. PMID- 27193747 TI - Clinical and Imaging Findings in an Infant With Zika Embryopathy. AB - Recent Zika virus (ZIKV) outbreaks have been associated with an increased incidence of neonatal microcephaly. Subsequently, tropism for the brain was established in human fetal brain tissue. We present the first congenital ZIKV infection in the United States, confirmed by high ZIKV immunoglobulin M antibody titers in serum and cerebrospinal fluid. The phenotypic characteristics of the patient fall within fetal brain disruption sequence, suggesting impaired brain development in the second half of gestation. Brain imaging revealed an almost agyric brain with diffuse parenchymal calcifications, hydrocephalus ex vacuo, and cerebellar hypoplasia. Ophthalmologic examination revealed macular pigment stippling and optic nerve atrophy. Liver, lungs, heart, and bone marrow were not affected. The patient had progressive neurologic deterioration in the first month of life. The discovery of ZIKV infection in human fetal brain tissue along with serologic confirmation proves the vertical transmission of ZIKV. Therefore, ZIKV has joined the group of congenital infections. PMID- 27193746 TI - Longitudinal Study of the Effects of Bacteremia and Sepsis on 5-year Risk of Cardiovascular Events. AB - BACKGROUND: The long-term and cumulative effect of multiple episodes of bacteremia and sepsis across multiple hospitalizations on the development of cardiovascular (CV) events is uncertain. METHODS: We conducted a longitudinal study of 156 380 hospitalizations in 47 009 patients (>=18 years old) who had at least 2 inpatient admissions at an academic tertiary care center in St Louis, Missouri, from 1 January 2008 through 31 December 2012. We used marginal structural models, estimated by inverse probability weighting (IPW) of bacteremia or sepsis and IPW of censoring, to estimate the marginal causal effects of bacteremia and sepsis on developing the first observed incident CV event, including stroke, transient ischemic attack, and myocardial infarction (MI), during the study period. RESULTS: Bacteremia and sepsis occurred during 4923 (3.1%) and 5544 (3.5%) hospitalizations among 3932 (8.4%) and 4474 (9.5%) patients, respectively. CV events occurred in 414 (10.5%) and 538 (12.0%) patients with prior episodes of bacteremia or sepsis, respectively, vs 3087 (7.2%) and 2963 (7.0%) patients without prior episodes of bacteremia or sepsis. The causal odds of experiencing a CV event was 1.52-fold (95% confidence interval [CI], 1.21- to 1.90-fold) and 2.39-fold (95% CI, 1.88- to 3.03-fold) higher in patients with prior instances of bacteremia or sepsis, respectively, compared to those without. Prior instances of septic shock resulted in a 6.91-fold (95% CI, 5.34- to 8.93-fold) increase in the odds of MI. CONCLUSIONS: Prior instances of bacteremia and sepsis substantially increase the 5-year risk of CV events. PMID- 27193748 TI - A Single-dose Zoledronic Acid Infusion Prevents Antiretroviral Therapy-induced Bone Loss in Treatment-naive HIV-infected Patients: A Phase IIb Trial. AB - BACKGROUND: Human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) are associated with bone loss leading to increased fracture rate among HIV-infected individuals. ART-induced bone loss is most intense within the first 48 weeks of therapy, providing a window for prophylaxis with long-acting antiresorptives. METHODS: In a phase 2, double-blind, placebo-controlled trial, we randomized 63 nonosteoporotic, ART-naive adults with HIV initiating ART with atazanavir/ritonavir + tenofovir/emtricitabine to a single zoledronic acid (ZOL) infusion (5 mg) vs placebo to determine the efficacy of ZOL in mitigating ART induced bone loss. Plasma bone turnover markers and bone mineral density (BMD) were performed at weeks 0, 12, 24, and 48 weeks. Primary outcome was change in C terminal telopeptide of collagen at 24 weeks. Repeated-measures analyses using mixed linear models were used to estimate and compare study endpoints. RESULTS: The ZOL arm had a 65% reduction in bone resorption relative to the placebo arm at 24 weeks (0.117 ng/mL vs 0.338 ng/mL; P < .001). This effect of ZOL occurred as early as 12 weeks (73% reduction; P < .001) and persisted through week 48 (57% reduction; P < .001). The ZOL arm had an 8% higher lumbar spine BMD at 12 weeks relative to the placebo arm (P = .003), and remained 11% higher at 24 and 48 weeks. Similar trends were observed in the hip and femoral neck. CONCLUSIONS: A single dose of ZOL administered at ART initiation prevented ART-induced bone loss through the first 48 weeks of ART, the period when ART-induced bone loss is most pronounced. Validation of these results in larger multicenter randomized clinical trials is warranted. CLINICAL TRIALS REGISTRATION: NCT01228318. PMID- 27193749 TI - Factors Underlying Ebola Virus Infection Among Health Workers, Kenema, Sierra Leone, 2014-2015. AB - BACKGROUND: Ebola virus disease (EVD) in health workers (HWs) has been a major challenge during the 2014-2015 outbreak. We examined factors associated with Ebola virus exposure and mortality in HWs in Kenema District, Sierra Leone. METHODS: We analyzed data from the Sierra Leone National Viral Hemorrhagic Fever Database, contact tracing records, Kenema Government Hospital (KGH) staff and Ebola Treatment Unit (ETU) rosters, and burial logs. RESULTS: From May 2014 through January 2015, 600 cases of EVD originated in Kenema District, including 92 (15%) HWs, 66 (72%) of whom worked at KGH. Among KGH medical staff and international volunteers, 18 of 62 (29%) who worked in the ETU developed EVD, compared with 48 of 83 (58%) who worked elsewhere in the hospital. Thirteen percent of HWs with EVD reported contact with EVD patients, while 27% reported contact with other infected HWs. The number of HW EVD cases at KGH declined roughly 1 month after implementation of a new triage system at KGH and the opening of a second ETU within the district. The case fatality ratio for HWs and non-HWs with EVD was 69% and 74%, respectively. CONCLUSIONS: The cluster of HW EVD cases in Kenema District is one of the largest ever reported. Most HWs with EVD had potential virus exposure both inside and outside of hospitals. Prevention measures for HWs must address a spectrum of infection risks in both formal and informal care settings as well as in the community. PMID- 27193751 TI - Molten salt CO2 capture and electro-transformation (MSCC-ET) into capacitive carbon at medium temperature: effect of the electrolyte composition. AB - Electrochemical transformation of CO2 into functional materials or fuels (i.e., carbon, CO) in high temperature molten salts has been demonstrated as a promising way of carbon capture, utilisation and storage (CCUS) in recent years. In a view of continuous operation, the electrolysis process should match very well with the CO2 absorption kinetics. At the same time, in consideration of the energy efficiency, a molten salt electrochemical cell running at lower temperature is more beneficial to a process powered by the fluctuating renewable electricity from solar/wind farms. Ternary carbonates (Li : Na : K = 43.5 : 31.5 : 25.0) and binary chlorides (Li : K = 58.5 : 41.5), two typical kinds of eutectic melt with low melting points and a wide electrochemical potential window, could be the ideal supporting electrolyte for the molten salt CO2 capture and electro transformation (MSCC-ET) process. In this work, the CO2 absorption behaviour in Li2O/CaO containing carbonates and chlorides were investigated on a home-made gas absorption testing system. The electrode processes as well as the morphology and properties of carbon obtained in different salts are compared to each other. It was found that the composition of molten salts significantly affects the absorption of CO2, electrode processes and performance of the product. Furthermore, the relationship between the absorption and electro-transformation kinetics are discussed based on the findings. PMID- 27193750 TI - Benefit-risk Evaluation for Diagnostics: A Framework (BED-FRAME). AB - The medical community needs systematic and pragmatic approaches for evaluating the benefit-risk trade-offs of diagnostics that assist in medical decision making. Benefit-Risk Evaluation of Diagnostics: A Framework (BED-FRAME) is a strategy for pragmatic evaluation of diagnostics designed to supplement traditional approaches. BED-FRAME evaluates diagnostic yield and addresses 2 key issues: (1) that diagnostic yield depends on prevalence, and (2) that different diagnostic errors carry different clinical consequences. As such, evaluating and comparing diagnostics depends on prevalence and the relative importance of potential errors. BED-FRAME provides a tool for communicating the expected clinical impact of diagnostic application and the expected trade-offs of diagnostic alternatives. BED-FRAME is a useful fundamental supplement to the standard analysis of diagnostic studies that will aid in clinical decision making. PMID- 27193752 TI - Barriers to Cervical Cancer Screening and Prevention in Young Korean Immigrant Women: Implications for Intervention Development. AB - This study aimed to identify major barriers to Papanicolaou (Pap) test uptake and human papillomavirus (HPV) vaccine acceptability. Three focus groups with 16 young Korean immigrant women residing in a community in the Midwest were conducted. Braun and Clarke's six phases of thematic analysis were used to develop themes. Three major themes emerged as barriers: (a) limited knowledge about cervical cancer and preventive behaviors, (b) culture-specific barriers, and (c) low accessibility to health care services. These themes were multifactorial and interrelated barriers to Pap test uptake and HPV vaccine acceptability among young Korean immigrant women. These findings indicate that culturally tailored cervical cancer education is needed to promote Pap test uptake and HPV vaccination in this underserved population. PMID- 27193755 TI - Radiation-Induced Moyamoya Syndrome after Proton Beam Therapy in the Pediatric Patient: A Case Series. AB - Minimizing normal-tissue radiation exposure is especially important in the pediatric population as children appear to be particularly sensitive to postradiation vasculopathies after conventional photon radiotherapy. Given the limited scattering effect and low-dose radiation delivery to the surrounding tissues with proton beam radiotherapy, this modality is considered to be an effective treatment for pediatric skull-base tumors compared to conventional radiotherapy, and to have fewer adverse side effects. We report 2 cases of radiation-induced moyamoya syndrome following proton beam therapy in pediatric patients. To our knowledge, only a few other reported cases of radiation-induced moyamoya syndrome following proton beam therapy exist in the current literature. While rare, radiation-induced moyamoya syndrome can occur in the pediatric population with newer techniques like proton beam radiotherapy. Accordingly, patients and their families should be informed about this potential complication prior to all forms of radiation treatment. PMID- 27193753 TI - The effectiveness and safety of two prophylactic antibiotic regimes in hip fracture surgery. AB - Antibiotic prophylaxis with cefuroxime can reduce the incidence of deep wound infection (DWI) in hip-fracture surgery, but may increase the risk of C. difficile infection (CDI). An alternative is gentamicin with beta-lactam for which a question exists around clinical effectiveness and safety, given the gentamicin-associated nephrotoxicity particularly in the elderly and narrower sensitivity spectrum. We compared 744 consecutive patients (group I-cefuroxime) with 756 in group II (gentamicin + flucloxacillin) who were well matched. There were 4 cases of CDI in the cefuroxime prophylaxis, whereas none in flucloxacillin plus gentamicin (group II). There was a statistically significant (p = 0.036) increased DWI rate in group II (2.5 %) as compared to group I (1.1 %). However, after controlling for age, gender, ASA grade, surgeon grade, implant type and type of anaesthesia, there was no statistically significant difference between the two groups (p = 0.146). 8.5 % of group I and 16.5 % of group II developed AKI post-operatively (p = 0.023); however, 79 % of group I and 80 % of in group II had complete resolution of AKI prior to their discharge. Further, a significant increase in inpatient deaths (p = 0.057) in group II was observed, but not at 30 days (p = 0.378). PMID- 27193754 TI - Birth Outcomes in a Prospective Pregnancy-Birth Cohort Study of Environmental Risk Factors in Kuwait: The TRACER Study. AB - BACKGROUND: Rapid development and westernisation in Kuwait and other Gulf states have been accompanied by rising rates of obesity, diabetes, asthma, and other chronic conditions. Prenatal experiences and exposures may be important targets for intervention. We undertook a prospective pregnancy-birth cohort study in Kuwait, the TRansgenerational Assessment of Children's Environmental Risk (TRACER) Study, to examine prenatal risk factors for early childhood obesity. This article describes the methodology and results of follow-up through birth. METHODS: Women were recruited at antenatal clinical visits. Interviewers administered questionnaires during the pregnancy and collected and banked biological samples. Children are being followed up with quarterly maternal interviews, annual anthropometric measurements, and periodic collection of biosamples. Frequencies of birth outcomes (i.e. stillbirth, preterm birth, small and large for gestational age, and macrosomia) were calculated as a function of maternal characteristics and behaviours. RESULTS: Two thousand four hundred seventy-eight women were enrolled, and 2254 women were followed to delivery. Overall, frequencies of stillbirth (0.6%), preterm birth (9.3%), and small for gestational age (7.4%) were comparable to other developed countries, but not strongly associated with maternal characteristics or behaviours. Macrosomia (6.1%) and large for gestational age (23.0%) were higher than expected and positively associated with pre-pregnancy maternal overweight/obesity. CONCLUSIONS: A large birth cohort has been established in Kuwait. The collected risk factors and banked biosamples will allow examination of the effects of prenatal exposures on the development of chronic disease in children. Initial results suggest that maternal overweight/obesity before pregnancy should be targeted to prevent macrosomia and its associated sequelae of childhood overweight/obesity. PMID- 27193756 TI - A global meta-analysis on the ecological drivers of forest restoration success. AB - Two billion ha have been identified globally for forest restoration. Our meta analysis encompassing 221 study landscapes worldwide reveals forest restoration enhances biodiversity by 15-84% and vegetation structure by 36-77%, compared with degraded ecosystems. For the first time, we identify the main ecological drivers of forest restoration success (defined as a return to a reference condition, that is, old-growth forest) at both the local and landscape scale. These are as follows: the time elapsed since restoration began, disturbance type and landscape context. The time elapsed since restoration began strongly drives restoration success in secondary forests, but not in selectively logged forests (which are more ecologically similar to reference systems). Landscape restoration will be most successful when previous disturbance is less intensive and habitat is less fragmented in the landscape. Restoration does not result in full recovery of biodiversity and vegetation structure, but can complement old-growth forests if there is sufficient time for ecological succession. PMID- 27193757 TI - High relative frequency of SCA1 in Poland reflecting a potential founder effect. AB - Spinocerebellar ataxias (SCAs) have irregular distributions worldwide. SCA1 is the most frequent in Poland, and no cases of SCA3 of Polish origin has yet been identified. In view of such patterns of SCAs occurrence, the relative frequency, geographical distribution and a possible founder effect of SCA1 were investigated. DNA samples of 134 probands with SCA1 and 228 controls were analysed. The genotyping of four markers, D6S89, D6S109, D6S274, D6S288, around the ATXN1 gene (SCA1) and sequencing of the selected variant of D6S89 were performed. The relative frequency of SCA1 was 68 %. The studied SCA1 pedigrees were irregularly distributed, with the highest concentration in Central Poland. Haplotyping revealed the association of ATXN1 gene mutation with a 197-bp variant of D6S89 marker (63 % of probands) and with a 184-bp variant of DS6274 (50.7 % of probands). Out of 61 SCA1 probands from Mazowieckie, 41 carried the same 197-bp variant. SCA1 relative frequency in Poland shows the highest value compared with the data from other countries worldwide. Due to the association with the mutation obtained for the investigated markers and the SCA1 pedigrees concentration in Central Poland, we hypothesise that it represents a potential founder effect. PMID- 27193758 TI - First detection of Onchocerca lupi infection in dogs in southern Spain. AB - BACKGROUND: Onchocerca lupi causes ocular pathology of varying severity in dogs from south-western United States, western Europe and northern Asia. This filarioid has also been recognized as a zoonotic agent in Tunisia, Turkey, Iran and the USA, though the information about the biology and epidemiology of this infection is largely unknown. In Europe, O. lupi has been reported in dogs from Germany, Greece, Hungary, Portugal and Romania and in a cat from Portugal. The present study was designed to establish the occurrence of O. lupi in dogs in southwestern Spain. In the present study a total of 104 dogs of different breed, sex, and age living in a shelter in Huelva (SW Spain) were examined. Skin snip samples were collected using a disposable scalpel in the forehead and inter scapular regions and stored as aliquots in saline solution (0.5 ml) before light microscopy observation of individual sediments (20 MUl) and molecular examination. RESULTS: Of the 104 dogs examined, 5 (4.8 %) were skin snip-positive for O. lupi: two by microscopy and three by PCR. One of the O. lupi infected dogs showed neurological signs but ocular ultrasonography and/or MRI detected no abnormalities. CONCLUSIONS: This first report of O. lupi infection in dogs in southern Spain expands the range of geographical distribution of this parasite and sounds an alarm bell for practitioners and physicians working in that area. PMID- 27193759 TI - Mode of action of leucocin K7 produced by Leuconostoc mesenteroides K7 against Listeria monocytogenes and its potential in milk preservation. AB - OBJECTIVES: To investigate the mode of action of leucocin K7 against Listeria monocytogenes and to assess its inhibitory effect on Lis. monocytogenes in refrigerated milk. RESULTS: A bacteriocin-producing strain, Leuconostoc mesenteroides K7, was isolated from a fermented pickle. The bacteriocin, leucocin K7, exhibited antagonistic activity against Lis. monocytogenes with an MIC of 28 ug/ml. It was sensitive to proteaseS and displayed good thermal stability and broad active pH range. Leucocin K7 had no effect on the efflux of ATP from Lis. monocytogenes but triggered the efflux of K(+) and the intracellular hydrolysis of ATP. It also dissipated the transmembrane electrical potential completely and transmembrane pH gradient partially. It 80 AU/ml inhibited the growth of Lis. monocytogenes by 2.3-3.9 log units in milk; when combined with glycine (5 mg/ml), it completely eliminated viable Lis. monocytogenes over 7 days CONCLUSION: Leucocin K7 shows different mode of action from nisin and may have potential application in milk preservation. PMID- 27193760 TI - A rapid and efficient polyethylenimine-based transfection method to prepare lentiviral or retroviral vectors: useful for making iPS cells and transduction of primary cells. AB - OBJECTIVES: To improve the efficiency, reproducibility and consistency of the PEI based transfection method that is often used in preparation of recombinant lentiviral or retroviral vectors. RESULTS: The contributions to transfection efficiency of multi-factors including concentration of PEI or DNA, dilution buffer for PEI/DNA, manner to prepare PEI/DNA complexes, influence of serum, incubation time for PEI/DNA complexes, and transfection time were studied. Gentle mixing during the preparation of PEI/DNA transfection complexes is critical for a high transfection efficiency. PEI could be stored at room temperature or 4 degrees C, and most importantly, multigelation should be avoided. The transfection efficiency of the PEI-based new method in different types of cells, such as 293T, Cos-7, HeLa, HepG2, Hep3B, Huh7 and L02, was also higher than that of the previous method. After optimization, the titer of our lentiviral system or retroviral system produced by PEI-based new method was about 10- or 3-times greater than that produced by PEI-based previous method, respectively. CONCLUSION: We provide a rapid and efficient PEI-based method for preparation of recombinant lentiviral or retroviral vectors which is useful for making iPS cells as well as transduction of primary cell cultures. PMID- 27193761 TI - Characterization and biological activities of cyclic (1 -> 3, 1 -> 6)-beta glucans from Bradyrhizobium japonicum. AB - OBJECTIVE: To isolate cyclic (1 -> 3, 1 -> 6)-beta-glucan from Bradyrhizobium japonicum MTCC120, to characterize its structure and to study its biological activities. RESULTS: The degree of polymerization of cyclic (1 -> 3, 1 -> 6)-beta glucan varied between 10 and 13 and with substituents acetyl, succinyl and phosphocholine. The cyclic glucans showed bimodal particle size distribution, with hydrodynamic diameters of 1.92 and 231 nm corresponding to monomeric and aggregated cyclic glucans, respectively. SEM and TEM images showed that the glucans formed aggregates of nanorods. The glucans were biocompatible, exhibited good antioxidant activity and had the abilities to bind to Aniline Blue dye to form a fluorescence complex which was concentration dependent. CONCLUSION: The glucans isolated are cyclic and have good antioxidant activities, hence have potential application in food and pharmaceutical industries. Their dye binding ability could be exploited in medical imaging to reduce the cytotoxicity of the dyes. PMID- 27193762 TI - GPs are much more than gatekeepers. PMID- 27193763 TI - Disruption of Vector Host Preference with Plant Volatiles May Reduce Spread of Insect-Transmitted Plant Pathogens. AB - Plant pathogens can manipulate the odor of their host; the odor of an infected plant is often attractive to the plant pathogen vector. It has been suggested that this odor-mediated manipulation attracts vectors and may contribute to spread of disease; however, this requires further broad demonstration among vector-pathogen systems. In addition, disruption of this indirect chemical communication between the pathogen and the vector has not been attempted. We present a model that demonstrates how a phytophathogen (Candidatus Liberibacter asiaticus) can increase its spread by indirectly manipulating the behavior of its vector (Asian citrus psyllid, Diaphorina citri Kuwayama). The model indicates that when vectors are attracted to pathogen-infected hosts, the proportion of infected vectors increases, as well as, the proportion of infected hosts. Additionally, the peak of infected host populations occurs earlier as compared with controls. These changes in disease dynamics were more important during scenarios with higher vector mortality. Subsequently, we conducted a series of experiments to disrupt the behavior of the Asian citrus psyllid. To do so, we exposed the vector to methyl salicylate, the major compound released following host infection with the pathogen. We observed that during exposure or after pre exposure to methyl salicylate, the host preference can be altered; indeed, the Asian citrus psyllids were unable to select infected hosts over uninfected counterparts. We suggest mechanisms to explain these interactions and potential applications of disrupting herbivore host preference with plant volatiles for sustainable management of insect vectors. PMID- 27193764 TI - Condom Use in the Context of Main and Casual Partner Concurrency: Individual and Relationship Predictors in a Sample of Heterosexual African American Men. AB - Researchers have identified engagement in sexual concurrency, particularly when condom use is inconsistent, as a risk factor for HIV and other sexually transmitted infections. This risk is particularly salient in rural communities in which dense interconnection of sexual networks can promote the spread of sexually transmitted infections. The authors investigated individual and relationship factors that predict inconsistent condom use in the context of main and casual partner sexual concurrency among 176 rural African American men. The individual psychosocial factors investigated included impulsivity and anger/hostility. Relationship variables included fidelity expectations, criticism from partners, and relationship control in both main and casual relationships. No individual risk factors were associated with main partner inconsistent condom use; however, impulsivity and anger/hostility positively predicted inconsistent condom use with a casual partner. Relationship control in the main partnership predicted inconsistent condom use with the main partner. Criticism from the main partner positively predicted inconsistent condom use with a casual partner. Finally, expectations for a casual partner's fidelity positively predicted inconsistent condom use with that partner. These findings underscore the importance of considering the influence of one sexual partnership on behavior in another and of taking this complexity into account in the development of preventive interventions. PMID- 27193765 TI - Examining the Correlates of Online Health Information-Seeking Behavior Among Men Compared With Women. AB - This study aimed to identify and compare the demographic, health behavior, health status, and social media use correlates of online health-seeking behaviors among men and women. Cross-sectional self-report data were collected from 1,289 Australian adults participating in the Queensland Social Survey. Logistic regression analyses were used to identify the correlates of online health information seeking for men and women. Differences in the strength of the relation of these correlates were tested using equality of regression coefficient tests. For both genders, the two strongest correlates were social media use (men: odds ratio [ OR] = 2.57, 95% confidence interval [CI: 1.78, 3.71]; women: OR = 2.93, 95% CI [1.92, 4.45]) and having a university education (men: OR = 3.63, 95% CI [2.37, 5.56]; women: OR = 2.74, 95% CI [1.66, 4.51]). Not being a smoker and being of younger age were also associated with online health information seeking for both men and women. Reporting poor health and the presence of two chronic diseases were positively associated with online health seeking for women only. Correlates of help seeking online among men and women were generally similar, with exception of health status. Results suggest that similar groups of men and women are likely to access health information online for primary prevention purposes, and additionally that women experiencing poor health are more likely to seek health information online than women who are relatively well. These findings are useful for analyzing the potential reach of online health initiatives targeting both men and women. PMID- 27193767 TI - Down-regulatory mechanism of mammea E/BB from Mammea siamensis seed extract on Wilms' Tumor 1 expression in K562 cells. AB - BACKGROUND: Wilms' tumor 1 (WT1) is a biological marker for predicting leukemia progression. In this study, mammea E/BB, an active compound from Saraphi (Mammea siamensis) seed extract was examined for its effect on down-regulatory mechanism of WT1 gene expression, WT1 protein and mRNA stability, and cell proliferation in K562 cell line. METHODS: M. siamensis seeds were obtained from the region of Chiang Mai (North of Thailand). Mammea E/BB was extracted from seeds of M. siamensis. WT1 protein expression and stability were evaluated by Western blot analysis. WT1 mRNA stability was assessed by qRT-PCR. WT1-DNA binding and WT1 promoter activity were assayed by ChIP assay and luciferase-reporter assay, respectively. Cell cycle arrest was studied by flow cytometry. RESULTS: Treatment with mammea E/BB led to down-regulation of WT1 expression. The suppression of WT1 expression did not involve protein and mRNA degradation. Rather, WT1 protein was down-regulated through disruption of transcriptional auto-regulation of the WT1 gene. Mammea E/BB inhibited WT1-DNA binding at the WT1 promoter and decreased luciferase activity. It also disrupted c-Fos/AP-1 binding to the WT1 promoter via ERK1/2 signaling pathway and induced S phase cell cycle arrest in K562 cells. CONCLUSION: Mammea E/BB had pleotropic effects on kinase signaling pathways, resulting in inhibition of leukemia cell proliferation. PMID- 27193766 TI - Three-Dimensional Environment Sustains Morphological Heterogeneity and Promotes Phenotypic Progression During Astrocyte Development. AB - Astrocytes are critical for coordinating normal brain function by regulating brain metabolic homeostasis, synaptogenesis and neurotransmission, and blood brain barrier permeability and maintenance. Dysregulation of normal astrocyte ontogeny contributes to neurodevelopmental and neurodegenerative disorders, epilepsies, and adverse responses to injury. To achieve these multiple essential roles, astrocyte phenotypes are regionally, morphologically, and functionally heterogeneous. Therefore, the best regenerative medicine strategies may require selective production of distinct astrocyte subpopulations at defined maturation levels. However, little is known about the mechanisms that direct astrocyte diversity or whether heterogeneity is represented in biomaterials. In vitro studies report lack of normal morphologies and overrepresentation of the glial scar type of reactive astrocyte morphology and expression of markers, questioning how well the in vitro astrocytes represent glia in vivo and whether in vitro tissue engineering methods are suitable for regenerative medicine applications. Our previous work with neurons suggests that the three-dimensional (3D) environment, when compared with standard two-dimensional (2D) substrate, yields cellular and molecular behaviors that more closely approximately normal ontogeny. To specifically study the effects of dimensionality, we used purified glial fibrillary acidic protein (GFAP)-expressing primary cerebral cortical astrocyte cultures from single pups and characterized the cellular maturation profiles in 2D and 3D milieu. We identified four morphological groups in vitro: round, bipolar, stellate, and putative perivascular. In the 3D hydrogel culture environment, postnatal astrocytes transitioned from a population of nearly all round cells and very few bipolar cells toward a population with significant fractions of round, stellate, and putative perivascular cells within a few days, following the in vivo ontogeny. In 2D, however, the population shift from round and bipolar to stellate and perivascular was rarely observed. The transition to distinct cellular morphologies in 3D corresponded to the in vivo expression of phenotypic markers, supporting the generation of mature heterogeneous glial populations in vitro. This study presents quantitative data supporting that 3D culture is critical for sustaining the heterogeneity of astrocytes in vitro and for generating a representation of the in vivo portfolio of heterogeneous populations of astrocytes required for therapeutic interventions in neurodevelopmental disorders, epilepsy, and brain injury. PMID- 27193769 TI - [Fascicular ventricular tachycardia in a 49-year-old patient]. AB - We report a 49-year-old patient who presented with tachycardia in our emergency room. The 12-lead ECG showed a wide complex tachycardia with a heart rate of 234 beats per minute. After structural heart disease was excluded via echocardiography, coronary angiography and magnetic resonance imaging, an electrophysiological study was performed. During programmed ventricular stimulation, a fascicular tachycardia was induced, which was successfully treated by radiofrequency ablation. Fascicular ventricular tachycardia is a rare tachycardia that occurs in patients without structural heart disease. Radiofrequency ablation can be performed safely and shows a high success rate. Differential diagnoses of fascicular ventricular tachycardias are substrate-based ventricular tachycardia and supraventricular tachycardia. PMID- 27193770 TI - 2:1 AV block : The orphan of organizational guidelines for cardiac pacing. PMID- 27193768 TI - Dissemination of evidence-based cancer control interventions among Catholic faith based organizations: results from the CRUZA randomized trial. AB - BACKGROUND: The CRUZA randomized trial tested the efficacy of an organizational level intervention to increase the capacity of Catholic faith-based organizations (FBOs) serving Latinos to implement evidence-based strategies (EBS) for cancer control. METHODS: Thirty-one Catholic parishes were enrolled. Twenty were randomized to a "capacity enhancement" (CE) intervention and 11 to a "standard dissemination" (SD) condition. Each received a Program Implementation Manual and Toolkit of materials culturally adapted for FBOs with Latino audiences for five types of EBS recommended by the US Preventive Services Community Guide. CE parishes were offered a menu of capacity-building activities over a 3-month period, while SD parishes were provided a one-time consultation by an Intervention Specialist. Baseline and follow-up surveys compared the number and types of EBS offered. RESULTS: At baseline, only one parish had offered any cancer-related program in the prior year, yet a third (36 %) had offered some other type of health program or service. At post-intervention follow-up, all parishes offered a greater number of EBS. The only statistically significant difference between CE and SD groups was the number of parishes offering small media interventions (90 % in CE, 64 % in SD; p < 0.05). CONCLUSIONS: All parishes increased the number of cancer control activities offered to their members. These findings suggest that Catholic parishes may already have capacity to implement EBS if they are appropriately adapted and packaged and may only require low levels of support to carry out programming. Further research is needed to examine the extent to which program offerings continued after the period of grant funding. TRIAL REGISTRATION: Clinicaltrials.gov NCT01740219 . PMID- 27193771 TI - Kuttner Tumor: IgG4-Related Disease of the Submandibular Gland. AB - Kuttner tumor/chronic sclerosing sialadenitis is a fibroinflammatory process that characteristically involves the submandibular gland of patients with IgG4-related disease. Histologic examination is often important to make the diagnosis because of its nonspecific clinical and radiologic findings. Microscopically, Kuttner tumor should be distinguished from other entities such as extranodal marginal zone lymphoma, Sjogren's syndrome, and lymphoepithelial sialadenitis. The lesion is histologically well-demarcated with lobular architecture, extensive fibrosis, marked lymphoplasmacytic inflammation, formation of lymphoid follicles, acinar atrophy, and obliterative phlebitis, without the presence of lymphoepithelial lesions. The IgG4-to-IgG positive plasma cell ratio of >40 % is also an important feature to support the diagnosis of Kuttner tumor. Moreover, flow cytometry is helpful to exclude a lymphoproliferative process. Clinicians and pathologists should consider the diagnosis of Kuttner tumor in patients with elevated serum IgG4 level. Timely and accurate diagnosis is important for appropriate management. PMID- 27193772 TI - Evaluating Markers for Guiding Treatment. AB - BACKGROUND: The subpopulation treatment effect pattern plot (STEPP) is an appealing method for assessing the clinical impact of a predictive marker on patient outcomes and identifying a promising subgroup for further study. However, its original formulation lacked a decision analytic justification and applied only to a single marker. METHODS: We derive a decision-analytic result that motivates STEPP. We discuss the incorporation of multiple predictive markers into STEPP using risk difference, cadit, and responders-only benefit functions. RESULTS: Applying STEPP to data from a breast cancer treatment trial with multiple markers, we found that none of the three benefit functions identified a promising subgroup for further study. Applying STEPP to hypothetical data from a trial with 100 markers, we found that all three benefit functions identified promising subgroups as evidenced by the large statistically significant treatment effect in these subgroups. CONCLUSIONS: Because the method has desirable decision analytic properties and yields an informative plot, it is worth applying to randomized trials on the chance there is a large treatment effect in a subgroup determined by the predictive markers. PMID- 27193774 TI - A Systematic Review of Beliefs About Hypertension and its Treatment Among African Americans. AB - PURPOSE OF REVIEW: The prevalence of hypertension and uncontrolled hypertension is higher among African Americans than any other ethnicity in the USA. Certain patient medical beliefs may lead to adverse health behaviors. The aim of this study was to systematically review and narratively synthesize beliefs about hypertension among African Americans. RECENT FINDINGS: In a narrative review of 22 studies, many participants attributed hypertension to stress and fatty foods. Hypertension was perceived to be an episodic, symptomatic disease. Many patients exhibited a strong faith in the efficacy of medications, but used them as needed to treat perceived intermittent hypertensive episodes or infrequently to avoid addiction and dependence. Home remedies were often reported to be used concurrently to treat the folk disease "high blood" or in place of medications associated with unwanted effects. Nevertheless, participants were invested in treatment of hypertension to prevent long-term complications. Trends over time suggest that beliefs about hypertension among African Americans have change significantly and now reflect the currently accepted biomedical model. African American beliefs about hypertension may frequently differ from those of healthcare professionals. These results suggest that reconciliation of differences between patient and provider expectations for disease management may improve adherence to and acceptance of medical treatments among African Americans with hypertension. Nevertheless, discordant health beliefs are common among all patients and additional work to elucidate beliefs of other patient subgroups such as age and gender is warranted. PMID- 27193773 TI - Sympathetic Activation in Chronic Heart Failure: Potential Benefits of Interventional Therapies. AB - Heart failure (HF) is a major and growing public health problem. This condition is associated with poor prognosis, a high rate of mortality, frequent hospitalization and increasing costs to health care systems. Pharmacological approaches aimed at reducing morbidity and mortality in HF have primarily focused on inhibition of the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system (SNS), both of which have been associated with disease development, progression and adverse cardiovascular (CV) outcomes. The increasing number of hospitalizations for HF decompensation suggests the failure of available treatment options, indicating the necessity for alternative therapeutic approaches. Alongside pharmacological and cardiac resynchronization therapies in selected patients with arrhythmia, recent advancements in the management of HF have been directed at inhibiting relevant neurogenic pathways underlying disease development and progression. Initial evidence regarding the safety and effectiveness of interventional procedures suggests that HF patients may benefit from novel adjunctive therapies. Here we review the critical role of sympathetic activation in HF and the rationale for therapeutic interventions including device based and interventional approaches aimed at restoring autonomic neural balance in this condition. PMID- 27193775 TI - QTL mapping of grain yield and phosphorus efficiency in barley in a Mediterranean like environment. AB - KEY MESSAGE: Key QTLs were identified for P efficiency in barley. Phosphorus efficiency and grain yield can be improved simultaneously in breeding. An important breeding goal for many crop species is improved phosphorus (P) efficiency. As in many other crops, selection for P efficient barley varieties has been slow because of inconsistent definitions of P efficiency and unknown genetic controls of P efficiency. We used two criteria to assess P efficiency in a doubled haploid Commander/Fleet population: P responsiveness (estimated as the deviation from the regression of yield with added P against yield with no added P treatment) and PUE (relative yield). Phosphorus responsiveness, PUE and grain yield were phenotyped at 0 and 30 kg P/ha in five environments. Lines consistently responsive to 30 kg P/ha across environments had the highest yield at the two P rates, and P responsiveness showed significantly higher broad sense heritability than PUE in the materials we studied. Genotyping of the population was subjected to a 9,000 single nucleotide polymorphism array and quantitative trait loci (QTLs) for P responsiveness were mapped with yield at 30 kg P/ha, which are common QTLs for yield when P was not limiting growth. The largest QTL for P responsiveness was mapped to 7HL in 2 years. PUE varied from 31 to 124 % across environments and one of the QTLs for PUE was mapped with yield at 0 kg P/ha. Our results demonstrate P responsiveness and grain yield can be improved simultaneously under high-input agricultural systems, but breeding for high PUE varieties may need to explore landrace or wild barley germplasm for low P tolerant alleles. PMID- 27193776 TI - Independent value of image fusion in unenhanced breast MRI using diffusion weighted and morphological T2-weighted images for lesion characterization in patients with recently detected BI-RADS 4/5 x-ray mammography findings. AB - OBJECTIVES: The aim of this study was to evaluate the accuracy and applicability of solitarily reading fused image series of T2-weighted and high-b-value diffusion-weighted sequences for lesion characterization as compared to sequential or combined image analysis of these unenhanced sequences and to contrast- enhanced breast MRI. METHODS: This IRB-approved study included 50 female participants with suspicious breast lesions detected in screening X-ray mammograms, all of which provided written informed consent. Prior to biopsy, all women underwent MRI including diffusion-weighted imaging (DWIBS, b = 1500s/mm2). Images were analyzed as follows: prospective image fusion of DWIBS and T2 weighted images (FU), side-by-side analysis of DWIBS and T2-weighted series (CO), combination of the first two methods (CO+FU), and full contrast-enhanced diagnostic protocol (FDP). Diagnostic indices, confidence, and image quality of the protocols were compared by two blinded readers. RESULTS: Reading the CO+FU (accuracy 0.92; NPV 96.1 %; PPV 87.6 %) and the CO series (0.90; 96.1 %; 83.7 %) provided a diagnostic performance similar to the FDP (0.95; 96.1 %; 91.3 %; p > 0.05). FU reading alone significantly reduced the diagnostic accuracy (0.82; 93.3 %; 73.4 %; p = 0.023). CONCLUSIONS: MR evaluation of suspicious BI-RADS 4 and 5 lesions detected on mammography by using a non-contrast-enhanced T2-weighted and DWIBS sequence protocol is most accurate if MR images were read using the CO+FU protocol. KEY POINTS: * Unenhanced breast MRI with additional DWIBS/T2w-image fusion allows reliable lesion characterization. * Abbreviated reading of fused DWIBS/T2w-images alone decreases diagnostic confidence and accuracy. * Reading fused DWIBS/T2w-images as the sole diagnostic method should be avoided. PMID- 27193777 TI - Clinical significance of post-treatment 18F-fluorodeoxyglucose uptake in cervical lymph nodes in patients with diffuse large B-cell lymphoma. AB - OBJECTIVES: We assessed the clinical significance of FDG uptake in cervical lymph nodes after treatment of patients with DLBCL. METHODS: In total, 87 patients with DLBCL were enrolled. All patients had newly appeared FDG uptake in cervical lymph nodes on PET/CT during follow-up after cessation of therapy. Cervical lymph nodes were finally diagnosed as benign or malignant according to histopathological findings or follow-up PET. Clinical characteristics and PET findings were compared between groups and factors associated with malignant lesions were evaluated. RESULTS: Only 8 (9.2 %) patients with cervical lymph nodes with FDG uptake ultimately had malignancy. FDG uptake lymph nodes appeared significantly earlier in the malignant group than in patients with benign FDG uptake (p = 0.013). Primary nodal lymphoma was more frequent in patients with cancer spread than in those with benign FDG uptake in lymph nodes (p < 0.001). CONCLUSION: Most cervical lymph nodes with FDG uptake (about 91 %) appearing after treatment of malignant DLBCL were ultimately benign. The elapsed time between the end of therapy and the appearance of cervical lymph nodes with FDG uptake and the primary sites of lymphomas are helpful clues in determining which cases are malignant. KEY POINTS: * About 91 % appearing after treatment of DLBCL were benign. * Elapsed time between therapy and FDG uptake was associated with malignancy. * Primary sites of lymphoma are helpful clues to determine malignancy. PMID- 27193780 TI - Piloting a Commercial Model for Fortified Rice: Lessons Learned From Brazil. AB - BACKGROUND: Two billion people worldwide have micronutrient deficiencies. Food fortification is a proven intervention to increase essential micronutrient availability in diets without requiring consumer behavioral change. Fortification of rice has high potential reach; however, cost, technology, market, and cultural constraints have prevented its wider adoption. OBJECTIVE: From 2010 to 2014, PATH and Global Alliance for Improved Nutrition implemented a pilot project in Brazil testing a model to scale up rice fortification through commercial channels. The project focused on 5 areas: (1) building fortified rice kernel production capacity; (2) supply chain development; (3) distribution channel and market development; (4) demand generation; and (5) advocacy and knowledge dissemination. METHODS: Primary data were collected in 2 rounds of quantitative research 6 months apart and conducted in 2 regions in Brazil. Secondary data were sourced from published literature, socioeconomic and demographic data, and sales figures from the project's rice miller partner. Postmortem analysis was conducted by the project team with input from external sources. RESULTS: Although the project successfully launched a fortified rice product and a category brand platform, it was unsuccessful in reaching meaningful scale. Market and industry dynamics affected producers' willingness to launch new fortified products. Consumers' strong attachment to rice combined with a weak understanding of micronutrient malnutrition hampered demand creation efforts. CONCLUSION: This project showed that a purely commercial approach is insufficient for sustainable scale-up of fortified rice to achieve public health goals in a 3- to 5-year period. PMID- 27193778 TI - 4D flow MR imaging of the portal venous system: a feasibility study in children. AB - OBJECTIVES: To determine the feasibility of 4D flow MRI for visualization and quantification of the portal venous haemodynamics in children and young adults. METHODS: 4D flow was performed in 28 paediatric patients (median age, 8.5 years; interquartile range, 5.2-16.5), 15 with non-operated native portal system and 13 with surgically created portal shunt. Image quality assessment for 3D flow visualization and flow pattern analyses was performed. Regional 4D flow peak velocity and net flow were compared with 2D-cine phase contrast MRI (2D-PC MR) in the post-surgical patients. RESULTS: Mean 3D flow visualization quality score was excellent (mean +/- SD, 4.2 +/- 0.9) with good inter-rater agreement (kappa,0.67). Image quality in children aged >10 years was better than children <=10 years (p < 0.05). Flow pattern was defined for portal, superior mesenteric, splenic veins and splenic artery in all patients. 4D flow and 2D-PC MR peak velocity and net flow were similar with good correlation (peak velocity: 4D flow 22.2 +/- 9.1 cm/s and 2D-PC MR 25.2 +/- 11.2 cm/s, p = 0.46; r = 0.92, p < 0.0001; net flow: 4D flow 9.5 +/- 7.4 ml/s and 2D-PC MR 10.1 +/- 7.3 ml/s, p = 0.65; r = 0.81, p = 0.0007). CONCLUSIONS: 4D flow MRI is feasible and holds promise for the comprehensive 3D visualization and quantification of portal venous flow dynamics in children and young adults. KEY POINTS: * 4D flow MRI is feasible in children and young adults. * 4D flow MRI has the ability to non invasively characterize portal haemodynamics. * Image quality of 4D flow MRI is better is older children. * 4D flow MRI can accurately quantify portal flow compared to 2D-cine PC MRI. PMID- 27193779 TI - Value of CT scan-assessed tibial tuberosity-trochlear groove distance in identification of patellar instability. AB - PURPOSE: Tibial tuberosity-trochlear groove (TTTG) distance is currently considered as one of the main factors in decision-making for surgical intervention in patients with patellar instability. The current study aimed to provide a valid comparison of TTTG distance in the healthy knees with those with patellar instability. MATERIALS AND METHODS: Patients with a history of two or more episodes of patellar dislocation in the same knee who were referred to our department for the assessment of TTTG distance were included. Asymptomatic knees of patients as well as both knees of 21 healthy individuals were used as controls. RESULTS: A total number of 42 patients, including 14 (33.3 %) male and 28 (66.7 %) female, with a mean age of 28.6 +/- 12.3 years were included. Twenty one controls with no significant difference of personal characteristics with patients were also enrolled. The mean TTTG distance in symptomatic and asymptomatic knees of patients were 18.71 +/- 3.96 mm and 17.35 +/- 4.39 mm with no significant difference (P = 0.298). The mean TTTG distances of both symptomatic and asymptomatic knees of patients were significantly higher than in knees of controls (P < 0.001). CONCLUSION: The findings of the current study are not in favor of considering TTTG distance independently in decision-making for surgical interventions. However, greater TTTG in both asymptomatic and symptomatic knees of patients compared to controls indicates that this measure could still be considered as an indicator of knee instability and even the need for surgery if considered in addition to other factors. PMID- 27193781 TI - Transplantation of Human Adipose Mesenchymal Stem Cells in Non-Immunosuppressed GRMD Dogs is a Safe Procedure. AB - The possibility to treat Duchenne muscular dystrophy (DMD), a lethal X-linked disorder, through cell therapy with mesenchymal stromal cells (MSCs) has been widely investigated in different animal models. However, some crucial questions need to be addressed before starting human therapeutic trials, particularly regarding its use for genetic disorders. How safe is the procedure? Are there any side effects following mesenchymal stem cell transplantation? To address these questions for DMD the best model is the golden retriever muscular dystrophy dog (GRMD), which is the closest model to the human condition displaying a much longer lifespan than other models. Here we report the follow-up of 5 GRMD dogs, which were repeatedly transplanted with human adipose-derived mesenchymal stromal cells (hASC), derived from different donors. Xenogeneic cell transplantation, which was done without immunosuppression, was well tolerated in all animals with no apparent long-term adverse effect. In the present study, we show that repeated heterologous stem-cell injection is a safe procedure, which is fundamental before starting human clinical trials. PMID- 27193783 TI - A population-based temporal logic gate for timing and recording chemical events. AB - Engineered bacterial sensors have potential applications in human health monitoring, environmental chemical detection, and materials biosynthesis. While such bacterial devices have long been engineered to differentiate between combinations of inputs, their potential to process signal timing and duration has been overlooked. In this work, we present a two-input temporal logic gate that can sense and record the order of the inputs, the timing between inputs, and the duration of input pulses. Our temporal logic gate design relies on unidirectional DNA recombination mediated by bacteriophage integrases to detect and encode sequences of input events. For an E. coli strain engineered to contain our temporal logic gate, we compare predictions of Markov model simulations with laboratory measurements of final population distributions for both step and pulse inputs. Although single cells were engineered to have digital outputs, stochastic noise created heterogeneous single-cell responses that translated into analog population responses. Furthermore, when single-cell genetic states were aggregated into population-level distributions, these distributions contained unique information not encoded in individual cells. Thus, final differentiated sub-populations could be used to deduce order, timing, and duration of transient chemical events. PMID- 27193785 TI - Practical aspects of prostate MRI: hardware and software considerations, protocols, and patient preparation. AB - The use of multiparametric MRI scans for the evaluation of men with prostate cancer has increased dramatically and is likely to continue expanding as new developments come to practice. However, it has not yet gained the same level of acceptance of other imaging tests. Partly, this is because of the use of suboptimal protocols, lack of standardization, and inadequate patient preparation. In this manuscript, we describe several practical aspects of prostate MRI that may facilitate the implementation of new prostate imaging programs or the expansion of existing ones. PMID- 27193782 TI - Role of Pericellular Matrix in the Regulation of Cancer Stemness. AB - Cancer stem cells (CSC) are a prominent component of the tumor bulk and extensive research has now identified them as the subpopulation responsible for tumor relapse and resistance to anti-cancer treatments. Surrounding the bulk formed of tumor cells, an extracellular matrix contributes to cancer growth; the main component of the tumor micro-environment is hyaluronan, a large disaccharide forming a molecular network surrounding the cells. The hyaluronan-dependent coat can regulate cell division and motility in cancer progression and metastasis. One of the receptors of hyaluronan is CD44, a surface protein frequently used as a CSC marker. Indeed, tumor cells with high levels of CD44 appear to exhibit CSC properties and are characterized by elevated relapse rate. The CD44-hyaluronan dependent interactions are Janus-faced: on one side, they have been shown to be crucial in both malignancy and resistance to therapy; on the other, they represent a potential value for future therapies, as disturbing the CD44 hyaluronan axis would not only impair the pericellular matrix but also the subpopulation of self-renewing oncogenic cells. Here, we will review the key roles of HA and CD44 in CSC maintenance and propagation and will show that CSC like spheroids from a rabdhomyosarcoma cell line, namely RD, have a prominent pericellular coat necessary for sphere formation and for elevated migration. Thus, a better understanding of the hyaluronan-CD44 interactions holds the potential for ameliorating current cancer therapies and eradicating CSC. PMID- 27193786 TI - Multiparametric prostate MRI: focus on T2-weighted imaging and role in staging of prostate cancer. AB - Multiparametric MRI (mpMRI) represents a growing modality for the non-invasive evaluation of prostate cancer (PCa) and is increasingly being used for patients with persistently elevated PSA and prior negative biopsies, for monitoring patients in active surveillance protocols, for preoperative characterization of cancer for surgical planning, and in planning for MRI-targeted biopsy. The focus of this work is twofold. First, we review the key role of T2-weighted imaging (T2WI) in mpMRI, specifically outlining how it is used for anatomic evaluation of the prostate, detection of clinically significant PCa, assessment of extraprostatic extension (EPE), and mimics of PCa on this sequence. We will also discuss optimal technical acquisition parameters for this sequence and recent technical advancements in T2WI. Second, we will delineate the role that mpMRI plays in the staging of PCa and describe the implications of the information that mpMRI can provide in determining the most appropriate management plan for the patient with PCa. PMID- 27193784 TI - Translation elicits a growth rate-dependent, genome-wide, differential protein production in Bacillus subtilis. AB - Complex regulatory programs control cell adaptation to environmental changes by setting condition-specific proteomes. In balanced growth, bacterial protein abundances depend on the dilution rate, transcript abundances and transcript specific translation efficiencies. We revisited the current theory claiming the invariance of bacterial translation efficiency. By integrating genome-wide transcriptome datasets and datasets from a library of synthetic gfp-reporter fusions, we demonstrated that translation efficiencies in Bacillus subtilis decreased up to fourfold from slow to fast growth. The translation initiation regions elicited a growth rate-dependent, differential production of proteins without regulators, hence revealing a unique, hard-coded, growth rate-dependent mode of regulation. We combined model-based data analyses of transcript and protein abundances genome-wide and revealed that this global regulation is extensively used in B. subtilis We eventually developed a knowledge-based, three step translation initiation model, experimentally challenged the model predictions and proposed that a growth rate-dependent drop in free ribosome abundance accounted for the differential protein production. PMID- 27193787 TI - DCE MRI of prostate cancer. AB - DCE MRI is an established component of multi-parametric MRI of the prostate. The sequence highlights the vascularization of cancerous lesions, allowing readers to corroborate suspicious findings on T2W and DW MRI and to note subtle lesions not visible on the other sequences. In this article, we review the technical aspects, methods of evaluation, limitations, and future perspectives of DCE MRI. PMID- 27193788 TI - Prostate cancer post-treatment follow-up and recurrence evaluation. AB - Recurrent prostate cancer following primary treatment is common, and the population of men with biochemical recurrence is complex. Conventional management of recurrent prostate cancer involves nontargeted and/or systemic therapies, without defining an individual patient's specific disease. However, recent advances in imaging enable a shift in the management of recurrent prostate cancer to targeted, patient-specific approaches. Specifically, MRI can detect and define local prostate cancer recurrence early in the course of disease, and prostate specific PET imaging greatly improves nodal staging and can detect previously unknown distant metastases. The significant advances in the imaging of both local and distant tumor recurrences allows for specific selection of treatment options tailored to patients and their disease with less associated morbidity. PMID- 27193790 TI - Zoomed echo-planar diffusion tensor imaging for MR tractography of the prostate gland neurovascular bundle without an endorectal coil: a feasibility study. AB - PURPOSE: The purpose of this study was to assess the feasibility of zoomed echo planar imaging (EPI) diffusion tensor imaging (DTI) with 2-channel parallel transmission (pTx) for MR tractography of the periprostatic neurovascular bundle (NVB) without an endorectal coil, and to compare its performance to that of conventionally acquired DTI. METHODS: 8 healthy males (28.9 +/- 4.6 years) underwent pelvic phased-array coil prostate MRI on a 3T system using both zoomed EPI DTI (z-DTI) with 2-channel pTx and conventional single-shot spin-echo EPI DTI (c-DTI) acquisitions with 6 encoding directions and b-values of 0 and 1000 s/mm(2). Fractional anisotropy (FA) maps and tractography analysis incorporating 3D visualization of the NVB were performed from each acquisition. Fiber tract counts, estimated signal-to-noise ratio (eSNR), and image quality measures of the FA maps and NVB tractography were compared. Quantitative and image quality measures were compared using Wilcoxon signed rank tests. RESULTS: 3 of 8 subjects had no tracts detected with c-DTI acquisition, while all 8 had tracts detected with z-DTI. z-DTI acquisition yielded significantly more fiber tracts (c-DTI: 77 +/- 116 tracts; z-DTI: 430 +/- 228 tracts; p = 0.019) and higher eSNR (c-DTI: 2.9 +/- 1.2; z-DTI: 13.17 +/- 9.9; p = 0.014). Relative to c-DTI acquisitions, z-DTI FA maps showed significantly reduced artifact (p = 0.008) and reduced anatomic distortion of the prostate (p = 0.010), while z-DTI tractography showed significantly better overall visual quality (p = 0.011), tract symmetry (p = 0.010), tract coherence (p = 0.011), and subjective similarity to the actual NVB (p = 0.011). CONCLUSION: Zoomed-EPI DTI acquisition for tractography of the prostate gland NVB improves quantitative and qualitative measures of image and tract fiber quality, allowing tractography of the NVB at 3T without using an endorectal coil. PMID- 27193789 TI - Positron emission tomography in imaging evaluation of staging, restaging, treatment response, and prognosis in prostate cancer. AB - Prostate cancer is a prevalent public health problem worldwide. While imaging has played a major role in this disease, there still remain many challenges and opportunities. Positron emission tomography with various physiologically based radiotracers is fundamentally suited to interrogate this biologically and clinically heterogeneous disease along the course of its natural history. In this article, I review briefly the published evidence for the use of positron emission tomography with 18F-fluorodeoxyglucose, 11C-acetate, and 18F- or 11C-choline in the imaging evaluation of prostate cancer. Although the focus of the article will be on these radiotracers given the accumulated experience with them, but I will also comment on the outlook for the use of other emerging PET radiotracers such as those targeted to the prostate-specific membrane antigen and the amino acid metabolism pathway. It is anticipated that PET will play major role in the evaluation of prostate cancer in the current evidence-based medicine environment. There will also be exciting novel prospects for the use of therapeutic-diagnostic (theransotic) pairs in the management of patients with prostate cancer. PMID- 27193791 TI - Can DW-MRI, with its ADC values, be a reliable predictor of biopsy outcome in patients with suspected prostate cancer? AB - PURPOSE: To relate the multiparametric magnetic resonance imaging (mp-MRI) of patients with suspect peripheral prostate cancer (PCa) to the results of the subsequent biopsy: in particular to explore whether DWI and ADC can predict the biopsy outcome and to investigate the relation between ADC and Gleason score (GS). MATERIALS AND METHODS: 175 consecutive patients who underwent 1.5 T mp-MRI followed by prostate biopsy were retrospectively analyzed by two independent radiologists. ADC values were measured in the peripheral suspect lesion areas (ADCSL) and in the contralateral zones (ADCNSL) obtaining ADCnorm = ADCSL/ADCNSL. Results on T2W images, DWI, ADC values, and perfusion studies were matched to their corresponding biopsy. RESULTS: Negative DWI and T2W had 100% negative predictive value (NPV). When DWI was positive, ADCSL > 0.90 * 10 > 0.90 * 10(-3) mm(2)/s (ADCnorm > 0.60) identified by the ROC curve (AUC = 0.80) corresponded to NPV = 85%. In positive biopsies, ADCSL and ADCnorm decreased significantly from GS = 6 to GS >= 8 with Spearman coefficient rho = -0.40 and ROC curve AUC = 0.72. CONCLUSION: mp-MRI allows a reliable prediction of a negative biopsy through the values of DWI, T2W, and ADC. In positive biopsies, there is a moderate correlation between ADC and the various GS levels. PMID- 27193792 TI - Evaluation of the impact of computed high b-value diffusion-weighted imaging on prostate cancer detection. AB - PURPOSE: The purpose of this study was to compare high b-value (b = 2000 s/mm(2)) acquired diffusion-weighted imaging (aDWI) with computed DWI (cDWI) obtained using four diffusion models-mono-exponential (ME), intra-voxel incoherent motion (IVIM), stretched exponential (SE), and diffusional kurtosis (DK)-with respect to lesion visibility, conspicuity, contrast, and ability to predict significant prostate cancer (PCa). METHODS: Ninety four patients underwent 3 T MRI including acquisition of b = 2000 s/mm(2) aDWI and low b-value DWI. High b = 2000 s/mm(2) cDWI was obtained using ME, IVIM, SE, and DK models. All images were scored on quality independently by three radiologists. Lesions were identified on all images and graded for lesion conspicuity. For a subset of lesions for which pathological truth was established, lesion-to-background contrast ratios (LBCRs) were computed and binomial generalized linear mixed model analysis was conducted to compare clinically significant PCa predictive capabilities of all DWI. RESULTS: For all readers and all models, cDWI demonstrated higher ratings for image quality and lesion conspicuity than aDWI except DK (p < 0.001). The LBCRs of ME, IVIM, and SE were significantly higher than LBCR of aDWI (p < 0.001). Receiver Operating Characteristic curves obtained from binomial generalized linear mixed model analysis demonstrated higher Area Under the Curves for ME, SE, IVIM, and aDWI compared to DK or PSAD alone in predicting significant PCa. CONCLUSION: High b-value cDWI using ME, IVIM, and SE diffusion models provide better image quality, lesion conspicuity, and increased LBCR than high b-value aDWI. Using cDWI can potentially provide comparable sensitivity and specificity for detecting significant PCa as high b-value aDWI without increased scan times and image degradation artifacts. PMID- 27193793 TI - Rate of observation and inter-observer agreement for LI-RADS major features at CT and MRI in 184 pathology proven hepatocellular carcinomas. AB - PURPOSE: To compare frequency and inter-reader agreement for LI-RADS v2014 major features at CT vs. MRI in pathology-proven cases of hepatocellular carcinoma. METHODS: Pathology reports and imaging studies from patients having undergone liver transplant or hepatectomy for hepatocellular carcinoma were reviewed. Size, location, washout, and capsule appearance for each lesion were recorded by two radiologists. Cohen's kappa and intraclass correlation coefficients (ICC) were calculated. RESULTS: One hundred and thirty-four patients with 184 tumors were reviewed. Seventy-seven percentage of lesions were imaged by CT and 23% by MRI. No lesions were evaluated with both modalities. Mean lesion diameter was 2.6 +/- 1.3 cm (ICC = 0.92). Arterial phase hyperenhancement was seen in 86% of lesions (kappa = 0.75). Washout was seen in 82% of studies (kappa = 0.61). Arterial phase hyperenhancement and washout were seen equally at CT and MRI (p = 1.00 and 0.46, respectively). Capsule was infrequently observed (27%) but was seen more commonly at MRI (44%) than at CT (17%) with p = 0.002 and (kappa = 0.56). Forty-seven percent of lesions with at least one prior study met LI-RADS criteria for threshold growth. The rates of LI-RADS categories 3, 4, and 5 were 9%, 37%, and 54%, respectively. More 1-2 cm LI-RADS 5 lesions were seen at MRI (43%) than at CT (8%), p = 0.01. CONCLUSION: A combined LI-RADS 4/5 group was 91% sensitive for hepatocellular carcinoma. Arterial enhancement and washout were seen more frequently than capsule, the sole finding seen more frequently at MRI than at CT. Inter-reader reliability was substantial for arterial hyperenhancement and washout but moderate for capsule. Capsule remains an important finding in small arterially enhancing lesions (1-2 cm) which require a second major criterion to upgrade to a LI-RADS 5 lesion. PMID- 27193794 TI - Incidence and clinical sequelae of portal and hepatic venous thrombosis following percutaneous cryoablation of liver tumors. AB - PURPOSE: To assess the incidence and sequelae of portal and hepatic venous thrombosis after percutaneous cryoablation of hepatic tumors. METHODS: From November 1998 through December 2010, 223 hepatic tumors were cryoablated during 170 ablation procedures in 135 patients. 24-h post-procedure MR images were reviewed retrospectively by two abdominal radiologists in consensus to identify tumor ablations that developed one or more new portal or hepatic venous thromboses in or outside the ablation zone. On follow-up MRI and CT examinations the outcomes of thromboses were classified as resolved, partially recanalized, persistent, or propagated. RESULTS: Venous thrombosis developed in association with 54 (24%) of 223 tumor ablations treated during 53 (31%) ablation procedures in 39 (28.8%) patients (15 women, 24 men; age range 40-82 years, mean 59 years). Of these 54 thromboses, 49 (91%) were located in portal vein branches, four (7%) in both portal and hepatic vein branches, and one (2%) in a hepatic vein branch. Thrombosed veins were outside but abutted the ablation zone in 36 (66.7%), and within it in 18 (33.3%). On follow-up imaging (n = 49), thrombi resolved in 29 (59%), partially recanalized in two (4%), persisted in 18 (37%) and propagated from sub-segmental or segmental branches to the left or right portal branches in five (10%). No thrombus propagated to the main portal vein or inferior vena cava. CONCLUSION: Portal and hepatic vein branch thromboses are common in small branches following percutaneous cryoablation of hepatic tumors and most resolve spontaneously without sequelae. PMID- 27193795 TI - Differentiation of mass-forming intrahepatic cholangiocarcinoma from poorly differentiated hepatocellular carcinoma: based on the multivariate analysis of contrast-enhanced computed tomography findings. AB - PURPOSE: We aim to gain further insight into identifying differential radiological features of mass-forming intrahepatic cholangiocarcinoma (mICC) from poorly differentiated hepatocellular carcinoma (pHCC) on contrast-enhanced computed tomography (CT). MATERIALS AND METHODS: 107 patients with pathologically confirmed mICC (n = 48) and pHCC (n = 59) who had undergone preoperative contrast enhanced CT were enrolled. Qualitative analysis of CT images were evaluated for tumor demarcation, shape, presence of satellite nodules, capsular retraction, biliary involvement, intratumoral arteries, tortuous tumoral vessels, vascular invasion, portal vein tumor thrombus, arterial enhancement pattern, portal venous phase enhancement, and washout pattern. Quantitative analysis was performed for mean attenuation of tumor and tumor-to-liver contrast during each phase. The degree of arterial enhancement was graded based on quantitative measurements. RESULTS: A lobulated shape, indistinct margin, peripheral rim enhancement in the arterial phase, and the presence of bile duct dilatation were CT features favoring mICC, whereas a round shape, partially indistinct margin, heterogeneous enhancement in the arterial phase, washout pattern and the presence of tortuous tumoral vessels were CT features favoring pHCC in the univariate analysis (P < 0.05). Tumor-to-liver contrast of pHCC was greater than that of mICC during the arterial phase (P = 0.015). In the multivariate analysis, bile duct dilatation, tortuous tumoral vessels, and a washout pattern were independent CT features for distinguishing between the two types. (P = 0.003, P = 0.003, P = 0.044, respectively). CONCLUSION: The absence of a washout pattern and tortuous tumoral vessels and presence of bile duct dilatation are more indicative of mICC than of pHCC on contrast-enhanced CT. PMID- 27193796 TI - Optimal visualization of focal nodular hyperplasia: quantitative and qualitative evaluation of single and multiphasic arterial phase acquisition at 1.5 T MR imaging. AB - PURPOSE: To evaluate the qualitative and quantitative benefit of multiple arterial phase acquisitions for the depiction of hypervascularity in FNH explored MR imaging using an extracellular contrast agent. METHODS: Between 2007 and 2014, all patients who underwent MR imaging for the exploration of FNH were included. The protocol included a single or a triple arterial phase ("single" and "triple" group, respectively). Arterial phases were visually divided into four types: (1) angiographic, (2) early, (3) late, and (4) portal. Signal intensity on arterial phase images was visually recorded as intense, moderate, or low for each lesion. Lesion-to-liver contrast (LLC) and relative lesion enhancement (RE) were calculated and compared between the two groups using the Mann-Whitney test. RESULTS: Thirty-five women were included (mean 45-year old, range 20-66), with 50 FNH (mean size 30 mm). Single and triple groups included 20 patients (30 FNH) and 15 patients (20 FNH), respectively. Signal intensity was intense in all lesions in the triple group and in 22/30 (73%) in the single group (p = 0.041). Intense signals were more frequently found in the early arterial phase (p < 0.001). RE was not significantly different (1.78 +/- 0.84 vs. 1.98 +/- 1.81 p = 0.430, in the single and triple groups, respectively) but LLC was significantly higher in the triple group (0.32 +/- 0.10 vs. 0.22 +/- 0.10, p = 0.005). LLC was significantly higher in the first two arterial phases in the triple group (p < 0.001). CONCLUSION: Acquisition of three arterial phases improves the visualization of hypervascularity of FNH, as lesions show high visual signal intensity and contrast. Optimal visualization is obtained in the early arterial phase. PMID- 27193798 TI - The "Sausage" pancreas. PMID- 27193797 TI - The "gallbladder pearl necklace" sign. PMID- 27193799 TI - Inverted V sign. PMID- 27193800 TI - Dermoscopic and Immunohistochemical Changes in Acquired Melanocytic Nevi following Narrow-Band Ultraviolet B Therapy. AB - BACKGROUND: Acquired melanocytic nevi (AMN) have been reported to undergo morphological and dermoscopic changes following exposure to narrow-band ultraviolet B (NB-UVB) radiation. OBJECTIVE: To study the morphological, dermoscopic and immunohistochemical changes in AMN following NB-UVB radiation. METHODS: Suberythemogenic NB-UVB sessions were delivered to 40 patients with AMN. For each patient, a minimum of 2 nevi were selected. One nevus was surgically removed from each patient prior to sessions as control; for the other nevus, dermoscopic images were captured before and after NB-UVB sessions. The images were evaluated for changes. At the end, another nevus was surgically removed for immunohistochemical assessment of Ki-67 and melan-A. RESULTS: Our study showed a statistically significant increase in the size of AMN following NB-UVB radiation. Benign dermoscopic changes were observed. Statistically significant positive correlations were found between some dermoscopic findings and the total cumulative dose of NB-UVB. Immunohistochemical analysis did not show any significant change in the exposed AMN. CONCLUSION: AMN irradiated with repeated suberythemogenic doses of NB-UVB showed benign morphological and dermoscopic changes, and this was confirmed by our immunohistochemical study. PMID- 27193801 TI - Erratum to: Impaired orthostatic blood pressure recovery and cognitive performance at two-year follow up in older adults: The Irish Longitudinal Study on Ageing. PMID- 27193802 TI - Communication and Influencing for ED Professionals: A training programme developed in the emergency department for the emergency department. AB - OBJECTIVE: The objective of the present study is to develop and pilot a communication and influencing skills training programme that meets ED health professionals' needs at an urban district hospital. METHODS: Qualitative methods within a participatory action research framework were utilised. An interdisciplinary team guided the programme's design and development. A training needs analysis saw team meetings, interviews, focus groups and observations conducted across the ED. Thematic analysis of the data identified health professionals' communication and influencing challenges. The training needs analysis informed the training programme curriculum's development. The pilot programme involved an interdisciplinary group of seven health professionals across 5 * 2 h sessions over 3 months, followed by a post-training survey. RESULTS: Five themes of communication and influencing challenges were identified: participating in effective handovers, involving patients in bedside handovers, effectively communicating with interdepartmental colleagues, asking ED colleagues to do tasks and understanding ED colleagues' roles, expectations and assumptions. Based on these challenges, the formulated RESPECT model (which stands for Relationships, Expectations, Styles, Partnerships, Enquiry, Coaching and Teamwork) informed the training curriculum. The peer coaching model used in the training programme was highly regarded by participants. CONCLUSIONS: Communication and Influencing for ED ProfessionalsTM (Babel Fish Group Pty Ltd, Melbourne, Victoria, Australia) addresses a gap for communication programmes developed in the ED for the ED. Future research will evaluate the programme's impact in this ED. PMID- 27193803 TI - Coaxial Dual-wavelength Interferometric Method for a Thermal Infrared Focal-plane array with Integrated Gratings. AB - Uncooled infrared (IR) focal-plane-array (FPA) with both large sensing range and high sensitivity is a great challenge due to the limited dynamic range of the detected signals. A coaxial dual-wavelength interferometric system was proposed here to detect thermal-induced displacements of an ultrasensitive FPA based on polyvinyl-chloride(PVC)/gold bimorph cantilevers and carbon nanotube (CNT)-based IR absorbing films. By alternately selecting the two displacement measurements performed by lambda1 (=640 nm) and lambda2 (=660 nm), the temperature measuring range with greater than 50% maximum sensitivity can be extended by eight-fold in comparison with the traditional single-wavelength mode. Meanwhile, the relative measurement error over the full measuring range is below 0.4%. In addition, it offers a feasible approach for on-line and on-wafer FPA characterization with great convenience and high efficiency. PMID- 27193804 TI - A tale of two anomalies: fourth branchial cleft cyst with thyroid hemiagenesis. PMID- 27193805 TI - Does prenatal exposure to vitamin D-fortified margarine and milk alter birth weight? A societal experiment - CORRIGENDUM. PMID- 27193806 TI - Is the Fever for High Impact a Disadvantage for Systematists? PMID- 27193807 TI - Parasitoid Wasps in Flower Heads of Asteraceae in the Brazilian Cerrado: Taxonomical Composition and Determinants of Diversity. AB - This study provides the first survey of the parasitoid fauna reared in flower heads of Asteraceae in the Brazilian cerrado. We investigated the relative importance of herbivore richness and plant species commonness to differences in parasitoid species richness among the plant species. A total of 15,372 specimens from 192 morphospecies belonging to 103 genera of Hymenoptera were reared from the flower heads of 74 Asteraceae species. Chalcidoidea and Ichneumonoidea were the most common superfamilies, with Eulophidae and Braconidae as the main families of parasitoid wasps. Singletons and doubletons accounted for 45% of total parasitoid species richness. The number of parasitoid species per plant species ranged from 1 to 67, and the variation in parasitoid species richness among plants was mainly explained by the number of sites in which the plants were recorded. This study shows that there is a highly diversified fauna of Hymenoptera parasitoids associated with flower heads of Asteraceae in the Brazilian cerrado. Our findings suggest that the accumulation of parasitoid species on plants is mainly determined by the regional commonness of plant species rather than the number of herbivore species associated with the plants. PMID- 27193808 TI - Communities of Social Bees (Apidae: Meliponini) in Trap-Nests: the Spatial Dynamics of Reproduction in an Area of Atlantic Forest. AB - As most stingless bee species depend on preexisting cavities, principally tree hollows, nesting site availability may represent an important restriction in the structuring of their forest communities. The present study examined the spatial dynamics of stingless bee communities in an area of Atlantic Forest by evaluating their swarming to trap-nests. The field work was performed in the Michelin Ecological Reserve (MER) on the southeastern coast of the state of Bahia, Brazil. Seven hundred and twenty trap-nests were distributed within two forest habitats in advanced and initial stages of regeneration. The trap-nests were monitored between September 2009 and March 2011. Twenty-five trap-nests were occupied by five bee species, resulting in a capture ratio of 0.035 swarms/trap (approximately 0.14 swarms/ha), corresponding to 10 swarms/year (0.056 swarms/ha/year). According to previous study at MER, the most abundant species in natural nests were also the most common in trap-nests in the two forest habitats examined, with the exception of Melipona scutellaris Latreille. Swarms of higher numbers of species were captured in initial regeneration stage forests than in advanced regeneration stage areas, and differences in species compositions were significant between both habitats (p = 0.03); these apparent differences were not consistent, however, when considering richness (p = 0.14) and total abundance (p = 0.08). The present study suggests the existence of a minimum cavity size threshold of approximately 1 L for most local species of stingless bees and sustains the hypothesis of a mass effect of Tetragonisca angustula Latreille populations from surrounding disturbed habitats on the MER forest community in terms of propagule (swarm) pressure. Examining swarm densities with trap-nests can be a promising technique for comparative analyses of the carrying capacities of forest habitats for stingless bee colonies, as long as size thresholds of cavities for nesting are taken into consideration. PMID- 27193809 TI - Density and Distribution of Xylocopa Nests (Hymenoptera: Apidae) in Caatinga Areas in the Surroundings of Passion Fruit Crops. AB - Due to their importance as pollinators of many plant species, this study aimed to know the nest density, spatial distribution, and nesting substrates used by Xylocopa species in the Caatinga, a xerophilous vegetation of Northeastern Brazil. Three areas of Caatinga in the surroundings of passion fruit crops were sampled. The bee species found in these areas were Xylocopa grisescens Lepeletier and Xylocopa frontalis (Olivier). All nests were in Commiphora leptophloeos (Burseraceae) trees (n = 113). Phytosociological analysis showed that this tree species presented the highest absolute density (212.5 individuals/ha) and index of importance value (52.7). The distribution pattern of the C. leptophloeos was aggregated. The nests were located in dead and dried branches with an average diameter of 5.3 +/- 2.0 cm (n = 43). The mean number of nests/tree was 3.1 +/- 2.8 (n = 113). The less disturbed area showed 6.7 nests/ha and 4.2 nests/tree. In the disturbed areas, 0.9 nests/ha and 2.4 to 2.7 nests/tree were observed. The availability of substrate for nesting in the studied areas and its importance as a limiting factor for nesting are discussed. PMID- 27193810 TI - Insect Pests Occurring on Dacryodes edulis (Burseraceae) in Rural Areas in Gabon. AB - The inventory of pests occurring on Dacryodes edulis (Burseraceae) was carried out in rural areas in Gabon during 2009 and 2010. Yellow traps and visual observations were used to record weekly pests during the tree flowering stage, in five villages. Catches from yellow traps rose to 7,296 and 1,722 insect pests in 2009 and 2010, respectively, whereas records from visual observations corresponded to 1,812 and 171 insect pests in 2009 and 2010, respectively. During both years, abundance from traps and visual monitoring was significantly different between sampling sites (p < 0.05). The difference in pests' diversity between sampling sites was not significant (p > 0.05) according to traps, but significant (p <= 0.04) according to visual observations in 2010. Mecocorynus loripes Chevrolat (Coleoptera: Cucurlionidae) attacked the stem of D. edulis, while Oligotrophus sp. (Diptera: Cecidomyiidae), Pseudophacopteron serrifer Malenovsky and Burckhardt (Hemiptera: Phacopteronidae), and Selenothrips rubrocinctus Giard (Thysanopera: Thripidae) attacked leaves. Pseudonoorda edulis Maes and Poligui (Lepidoptera: Crambidae) and Lobesia aeolopa Meyrick (Lepidoptera: Tortricidae) infested fruits and inflorescences, respectively. These insects are specifically linked to plant patterns, and their identification provided the first basic information for developing suitable strategies to control pests of D. edulis in Gabon, as well as in neighboring central African countries. PMID- 27193811 TI - Competitive Interactions between Immature Stages of Bactrocera cucurbitae (Coquillett) and Bactrocera tau (Walker) (Diptera: Tephritidae) under Laboratory Conditions. AB - The melon fly, Bactrocera cucurbitae (Coquillett), and the pumpkin fly, Bactrocera tau (Walker), are economically important pests that attack mainly cucurbitacean fruits. The two fruit fly species have similar natural distributions, host ranges, and population growth capacities. This study was designed to assess the asymmetrical competitions through resource exploitation between the larvae of B. cucurbitae and B. tau at different density levels and temperatures, and on different hosts by comparing the relative effects of interspecific and intraspecific interactions on four life history parameters: survival rate, puparial mass, puparial duration, and developmental duration. Our results showed that intraspecific and interspecific competitions occurred under some laboratory conditions, and B. cucurbitae took advantage over B. tau at the high-density level and at low and high temperatures on pumpkin, bitter gourd, and bottle gourd when interspecific competition took place. Intraspecific and interspecific competitions mainly affected the puparial mass and the survival rate of the two fruit fly species but had no marked effect on the puparial duration or development duration. PMID- 27193812 TI - Morphology of the Pylorus of Bombyx mori (Linnaeus) (Lepidoptera: Bombycidae). AB - The pylorus is a segment of the hindgut of great morphological diversity, which is subdivided into the posterior interstitial ring, pyloric cone, and pyloric valve. There is no morphological information on Bombyx mori (L.) hybrids, which is an insect of economic interest to Brazil. Consequently, this study aimed to analyze the morphology of the pylorus of hybrid larvae of fifth instars of B. mori from crossbreeding of Chinese and Japanese races. These were anesthetized, and the pylorus was fixed and processed by light microscopy and scanning electron microscopy. The pylorus presented as a separate compartment, consisting of a simple epithelium, with large variation in cell morphology, covered on the luminal side by an intima with specializations in some areas, the spicules. The musculature was formed by bundles of striated muscle fibers in longitudinal and circular arrangement. These fibers were multinucleated with central and peripheral nuclei, operating in peristalsis. The morphology of the pylorus is a reflection of functional dynamism, and this study provided a better understanding of its physiology, which promotes the regulated movement of the bolus, preventing reflux and directing it towards the ileum in the formation of fecal pellets. PMID- 27193813 TI - A Review of the Genus Pielomastax Chang (Orthoptera: Eumastacoidea) from China with Description of a New Species. AB - The review of the genus Pielomastax is given. The genus consists of 14 species distributed in China. Pielomastax cladopygidium n. sp. is described from Shaanxi Province. An annotated list of species and key to species of Pielomastax is provided. PMID- 27193814 TI - No Detectable Trade-Offs Among Immune Function, Fecundity, and Survival via a Juvenile Hormone Analog in the House Cricket. AB - Hormones are key regulators of resource allocation among functions and thus play an important role in resource-based trade-offs. The juvenile hormone (JH) is an insect hormone that mediates resource allocation between immunity and life history components. Here, we have tested whether this is the case using the house cricket. We investigated whether increased levels of JH (using methoprene, a JH analog) enable an enhanced survival and fecundity (via egg number) at the cost of reduced hemocyte number (a trait that is associated with immune response in insects) in the house cricket, Acheta domesticus L. We had three groups of adult crickets of both sexes: experimental (methoprene and acetone), positive control (methoprene), and negative control (no manipulation). Prior to and after experimental treatments, we counted the number of hemocytes (for the case of both sexes) and recorded the number of eggs laid and survival of females after the manipulation. There was no difference in hemocyte number, egg number, and survival. These results do not support a JH-mediated trade-off among immune ability, survival, and fecundity. We provide arguments to explain the lack of JH mediated trade-offs in the house cricket. PMID- 27193816 TI - The Sharpshooter Genus Geitogonalia Young: Descriptions of a New Brazilian Species and of the Female of Geitogonalia quatuordecimmaculata (Taschenberg) (Hemiptera: Cicadellidae). AB - The sharpshooter genus Geitogonalia Young was so far known from a single species from Southeastern Brasil-Geitogonalia quatuordecimmaculata (Taschenberg). A new species, Geitogonalia viridis, is described and illustrated in this paper based on males and females from the state of Rio de Janeiro. In addition, the female of G. quatuordecimmaculata is for the first time described and illustrated in detail. Geitogonalia quatuordecimmaculata is a dark species marked with bright orange on the fore wings, whereas the new species has the corium and clavus of the fore wings mostly green. The paraphyses are well developed in G. quatuordecimmaculata, with elongate rami, whereas they are inconspicuous in G. viridis, with the rami modified as a pair of very small sclerites. PMID- 27193815 TI - Three Heat Shock Protein Genes from Bactrocera (Tetradacus) minax Enderlein: Gene Cloning, Characterization, and Association with Diapause. AB - Bactrocera (Tetradacus) minax Enderlein is a major pest to wild and cultivated species of citrus. Bactrocera minax produces one generation per year with a long pupal diapause period of over 6 months, which hinders efforts to obtain vast numbers of insects under standard room conditions. Determining the mechanisms of diapause is significantly important for obtaining large quantities of these insects. To characterize the heat shock protein (Hsp) genes of B. minax and to unravel their potential contribution to diapause, we performed 3' and 5' RACE to isolate the complementary DNA (cDNA) sequences, bioinformatics to examine the phylogenetic relationships, and real-time quantitative PCR to detect the expression patterns of three Hsp genes during various developmental stages. These results represent the first characterization of the three Hsp genes of B. minax; the open reading frames of Bmhsp23, Bmhsp70, and Bmhsp90 were 510, 1,911, and 1,089 bp, encoding 170, 636, and 363 amino acids, respectively. BmHsp70 and BmHsp90 displayed high identity to previously identified Hsp70 and Hsp90 genes, respectively. BmHsp23 displayed varying similarity, from 28 to 83%, to previously identified small Hsps. Bmhsp23 messenger RNA (mRNA) expression was found to be upregulated during diapause initiation, maintenance, and termination. Bmhsp70 mRNA expression peaked during diapause initiation. Bmhsp90 mRNA expression remained at a relatively low level during deep diapause. Our present results suggest that Bmhsp70 might play an important role in diapause initiation, while Bmhsp23 in diapause initiation and maintenance and Bmhsp90 in diapause regulation. These results improve our understanding of the mechanism of diapause in B. minax at the molecular level. PMID- 27193817 TI - Survival of Seasonal Flooding in the Amazon by the Terrestrial Insect Conotrachelus dubiae O'Brien & Couturier (Coleoptera: Curculionidae), a Pest of the Camu-Camu Plant, Myrciaria dubia (Myrtaceae). AB - The weevil Conotrachelus dubiae O'Brien & Couturier (Coleoptera: Curculionidae) is a pest of an economically important Amazonian fruit tree Myrciaria dubia (Myrtaceae). This tree grows in seasonally flooded environments, and how weevil larvae survive flooding has not been studied. From December 2004 to May 2009, five experiments were conducted in natural conditions and in the laboratory, with the aim of understanding the mechanisms that allow the survival of C. dubiae larvae in seasonal floods in Amazonia. The larvae of C. dubiae were kept under water for over 93 days. Older instars exposed to periodic circulation of water survived better than younger instars in addition to all larvae that were kept continuously under uncirculated water. Individuals that were collected from plots of M. dubia located in flooded soils and non-flooded soils did not exhibit statistically significant differences in their levels of survival indicating that the variation in survival of flooding events is due to phenotypic plasticity of the species and not to local adaptation by the populations in different environments. We speculate that larvae can survive floods without major physiological changes as larvae appear to obtain oxygen from water by cutaneous diffusion, assisted by caudal movements. PMID- 27193819 TI - De Novo Synthesis of Benzenoid Compounds by the Yeast Hanseniaspora vineae Increases the Flavor Diversity of Wines. AB - Benzyl alcohol and other benzenoid-derived metabolites of particular importance in plants confer floral and fruity flavors to wines. Among the volatile aroma components in Vitis vinifera grape varieties, benzyl alcohol is present in its free and glycosylated forms. These compounds are considered to originate from grapes only and not from fermentative processes. We have found increased levels of benzyl alcohol in red Tannat wine compared to that in grape juice, suggesting de novo formation of this metabolite during vinification. In this work, we show that benzyl alcohol, benzaldehyde, p-hydroxybenzaldehyde, and p-hydroxybenzyl alcohol are synthesized de novo in the absence of grape-derived precursors by Hanseniaspora vineae. Levels of benzyl alcohol produced by 11 different H. vineae strains were 20-200 times higher than those measured in fermentations with Saccharomyces cerevisiae strains. These results show that H. vineae contributes to flavor diversity by increasing grape variety aroma concentration in a chemically defined medium. Feeding experiments with phenylalanine, tryptophan, tyrosine, p-aminobenzoic acid, and ammonium in an artificial medium were tested to evaluate the effect of these compounds either as precursors or as potential pathway regulators for the formation of benzenoid-derived aromas. Genomic analysis shows that the phenylalanine ammonia-lyase (PAL) and tyrosine ammonia lyase (TAL) pathways, used by plants to generate benzyl alcohols from aromatic amino acids, are absent in the H. vineae genome. Consequently, alternative pathways derived from chorismate with mandelate as an intermediate are discussed. PMID- 27193818 TI - Tomato Yellow Leaf Curl Virus Benefits Population Growth of the Q Biotype of Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae). AB - Plant viruses can directly influence their insect vectors, and indirectly through their shared host plant, altering their behavior and performance in a mutualistic or rather antagonistic manner. One of the most studied begomovirus, Tomato yellow leaf curl virus (TYLCV), may also facilitate the expansion of its vector, the whitefly Bemisia tabaci (Gennadius). Considering the likely expansion of the disease and its major vector, we studied the direct and the indirect effects of a Mediterranean isolate of this virus (TYLCV-IL) on the biological performance of the Q biotype of B. tabaci. The following parameters were examined: development time and viability of nymphs, sex ratio, fecundity, and fertility and longevity. The results varied from positive to neutral depending on the parameter and the effect studied. TYLCV accelerated nymphal developmental and increased male longevity of B. tabaci when viruliferous insects developed on TYLCV-immune eggplants (direct effects). An indirect, positive effect of TYLCV-infected plants was observed on fecundity of B. tabaci, which laid more eggs on virus-infected than on noninfected tomato plants. Our results show that TYLCV enhances the population increase of its whitefly vector and that there is a high risk of rapid expansion of both the virus and its vector-the MED species of B. tabaci-into new areas when both agents interact together. PMID- 27193820 TI - High antiviral effects of hibiscus tea extract on the H5 subtypes of low and highly pathogenic avian influenza viruses. AB - Viral neuraminidase inhibitors are widely used as synthetic anti-influenza drugs for the prevention and treatment of influenza. However, drug-resistant influenza A virus variants, including H5N1 highly pathogenic avian influenza viruses (HPAIVs), have been reported. Therefore, the discovery of novel and effective antiviral agents is warranted. We screened the antiviral effects of 11 herbal tea extracts (hibiscus, black tea, tencha, rosehip tea, burdock tea, green tea, jasmine tea, ginger tea, lavender tea, rose tea and oak tea) against the H5N1 HPAIV in vitro. Among the tested extracts, only the hibiscus extract and its fractionated extract (frHibis) highly and rapidly reduced the titers of all H5 HPAIVs and low pathogenic AIVs (LPAIVs) used in the pre-treatment tests of Madin Darby canine kidney (MDCK) cells that were inoculated with a mixture of the virus and the extract. Immunogold electron microscopy showed that anti-H5 monoclonal antibodies could not bind to the deformed H5 virus particles pretreated with frHibis. In post-treatment tests of MDCK cells cultured in the presence of frHibis after infection with H5N1 HPAIV, the frHibis inhibited viral replication and the expression of viral antigens and genes. Among the plants tested, hibiscus showed the most prominent antiviral effects against both H5 HPAIV and LPAIV. PMID- 27193822 TI - FDA-approved drugs that interfere with laboratory tests: A systematic search of US drug labels. AB - Drug-related laboratory test interference or drug/laboratory test interactions (DLTI) are a major source of laboratory errors. DLTI is of concern with regard to both the clinical diagnosis and the monitoring of patients. Although there have been numerous reports about specific drugs that interfere with laboratory tests, there has not been a recent review on the topic. We herein provide a review of the known DLTI of US FDA-approved drugs based on a systematic search of DailyMed, a website containing the labels of US FDA-approved drugs. The labels for all human single-ingredient prescription drugs included in the database (1368) were searched using stemmed keywords and were manually reviewed for their relevance to DLTI. A total of 134 labels were positive, which indicated that the drug interferes with at least one clinical laboratory test. Antibacterial agents, psychotropic drugs and contrast media are the classes of drugs most likely to lead to DLTI. Urine was the clinical sample most frequently affected by DLTI. The FDA drug label is a source of information for studies of DLTI, although information is still lacking for most drugs, and additional improvements are needed for many of the existing records. Medical professionals, clinicians and laboratory staff should keep these possible interactions in mind when interpreting the results of laboratory tests, and should ensure that they obtain a complete and accurate record of all drugs being used by patients in order to anticipate potential DLTI. The development of a reporting system to address potential DLTI is warranted. PMID- 27193821 TI - Induction of apoptosis by HBI-8000 in adult T-cell leukemia/lymphoma is associated with activation of Bim and NLRP3. AB - Adult T-cell leukemia/lymphoma (ATL) is an aggressive T-cell malignancy caused by human T-cell lymphotropic virus 1. Treatment options for acute ATL patients include chemotherapy, stem cell transplantation, and recently the anti-chemokine (C-C motif) receptor 4 antibody, although most patients still have a poor prognosis and there is a clear need for additional options. HBI-8000 is a novel oral histone deacetylase inhibitor with proven efficacy for treatment of T-cell lymphomas that recently received approval in China. In the present study, we evaluated the effects of HBI-8000 on ATL-derived cell lines and primary cells obtained from Japanese ATL patients. In most cases HBI-8000 induced apoptosis in both primary ATL cells and cell lines. In addition, findings obtained with DNA microarray suggested Bim activation and, interestingly, the contribution of the NLR family, pyrin domain containing 3 (NLRP3) inflammasome pathway in HBI-8000 induced ATL cell death. Further investigations using siRNAs confirmed that Bim contributes to HBI-8000-induced apoptosis. Our results provide a rationale for a clinical investigation of the efficacy of HBI-8000 in patients with ATL. Although the role of NLRP3 inflammasome activation in ATL cell death remains to be verified, HBI-8000 may be part of a novel therapeutic strategy for cancer based on the NLRP3 pathway. PMID- 27193826 TI - Rhodium(i)-catalysed intermolecular alkyne insertion into (2 pyridylmethylene)cyclobutenes. AB - Cyclobutenes with 2-pyridylmethylene groups at the 3 position underwent an intermolecular alkyne insertion reaction in the presence of a rhodium(i) catalyst at 170 degrees C to afford substituted benzenes. Among the different 2 pyridylmethylene groups examined, 3-methyl-2-pyridyl derivatives showed superior activity and readily coupled with various alkynes, including sterically demanding, heteroaromatic and terminal alkynes. PMID- 27193824 TI - Identification and Characterization of miRNAs in Chondrus crispus by High Throughput Sequencing and Bioinformatics Analysis. AB - Chondrus crispus, an economically and medicinally important red alga, is a medicinally active substance and important for anti-tumor research. In this study, 117 C. crispus miRNAs (108 conserved and 9 novel) were identified from 2,416,181 small-RNA reads using high-throughput sequencing and bioinformatics methods. According to the BLAST search against the miRBase database, these miRNAs belonged to 110 miRNA families. Sequence alignment combined with homology searching revealed both the conservation and diversity of predicted potential miRNA families in different plant species. Four and 19 randomly selected miRNAs were validated by northern blotting and stem-loop quantitative real-time reverse transcription polymerase chain reaction detection, respectively. The validation rates (75% and 94.7%) demonstrated that most of the identified miRNAs could be credible. A total of 160 potential target genes were predicted and functionally annotated by Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes analysis. We also analyzed the interrelationship of miRNAs, miRNA-target genes and target genes in C. crispus by constructing a Cytoscape network. The 117 miRNAs identified in our study should supply large quantities of information that will be important for red algae small RNA research. PMID- 27193823 TI - Platelet-derived growth factor receptor/platelet-derived growth factor (PDGFR/PDGF) system is a prognostic and treatment response biomarker with multifarious therapeutic targets in cancers. AB - Progress in cancer biology has led to an increasing discovery of oncogenic alterations of the platelet-derived growth factor receptors (PDGFRs) in cancers. In addition, their overexpression in numerous cancers invariably makes PDGFRs and platelet-derived growth factors (PDGFs) prognostic and treatment markers in some cancers. The oncologic alterations of the PDGFR/PDGF system affect the extracellular, transmembrane and tyrosine kinase domains as well as the juxtamembrane segment of the receptor. The receptor is also involved in fusions with intracellular proteins and receptor tyrosine kinase. These discoveries undoubtedly make the system an attractive oncologic therapeutic target. This review covers elementary biology of PDGFR/PDGF system and its role as a prognostic and treatment marker in cancers. In addition, the multifarious therapeutic targets of PDGFR/PDGF system are discussed. Great potential exists in the role of PDGFR/PDGF system as a prognostic and treatment marker and for further exploration of its multifarious therapeutic targets in safe and efficacious management of cancer treatments. PMID- 27193825 TI - GRK5 Deficiency Leads to Selective Basal Forebrain Cholinergic Neuronal Vulnerability. AB - Why certain diseases primarily affect one specific neuronal subtype rather than another is a puzzle whose solution underlies the development of specific therapies. Selective basal forebrain cholinergic (BFC) neurodegeneration participates in cognitive impairment in Alzheimer's disease (AD), yet the underlying mechanism remains elusive. Here, we report the first recapitulation of the selective BFC neuronal loss that is typical of human AD in a mouse model termed GAP. We created GAP mice by crossing Tg2576 mice that over-express the Swedish mutant human beta-amyloid precursor protein gene with G protein-coupled receptor kinase-5 (GRK5) knockout mice. This doubly defective mouse displayed significant BFC neuronal loss at 18 months of age, which was not observed in either of the singly defective parent strains or in the wild type. Along with other supporting evidence, we propose that GRK5 deficiency selectively renders BFC neurons more vulnerable to degeneration. PMID- 27193827 TI - What contraception do women use after abortion? An analysis of 319,385 cases from eight countries. AB - Contraception is an essential element of high-quality abortion care. However, women seeking abortion often leave health facilities without receiving contraceptive counselling or methods, increasing their risk of unintended pregnancy. This paper describes contraceptive uptake in 319,385 women seeking abortion in 2326 public-sector health facilities in eight African and Asian countries from 2011 to 2013. Ministries of Health integrated contraceptive and abortion services, with technical assistance from Ipas, an international non governmental organisation. Interventions included updating national guidelines, upgrading facilities, supplying contraceptive methods, and training providers. We conducted unadjusted and adjusted associations between facility level, client age, and gestational age and receipt of contraception at the time of abortion. Overall, postabortion contraceptive uptake was 73%. Factors contributing to uptake included care at a primary-level facility, having an induced abortion, first-trimester gestation, age >=25, and use of vacuum aspiration for uterine evacuation. Uptake of long-acting, reversible contraception was low in most countries. These findings demonstrate high contraceptive uptake when it is delivered at the time of the abortion, a wide range of contraceptive commodities is available, and ongoing monitoring of services occurs. Improving availability of long-acting contraception, strengthening services in hospitals, and increasing access for young women are areas for improvement. PMID- 27193828 TI - Increasing incidence of Clostridium difficile infections: results from a 5-year retrospective study in a large teaching hospital in the Italian region with the oldest population. AB - Limited information is available on the incidence of Clostridium difficile infections (CDIs) in Italian hospitals. In this study, we assessed the changes in the incidence of CDI over a 5-year period in a teaching hospital in Liguria, the Italian region with the oldest population. Secondary endpoints were the development of severe CDI and 30-day mortality. The annual incidence of CDI/10000 patient-days significantly increased from 0.54 in 2010 to 3.04 in 2014 (chi 2 for trend, P < 0.001). The median age of patients with CDI was 81 years. As many as 81% and 89% of these patients had comorbid conditions and previous exposure to antibiotics, respectively. In the multivariate analysis of risk factors for severe CDI, previous therapy with histamine 2 blockers and low serum albumin were associated with severe CDI, while diabetes appeared to be protective. In the multivariate model of risk factors for 30-day mortality, high leukocyte count, low serum albumin, and increased serum creatinine were unfavourably associated with outcome. Strict adherence to infection control measures was of utmost importance to counteract the increasing incidence of CDI in our hospital, particularly because of the advanced age of the patients and their very high frequency of chronic conditions and use of antibiotics, which readily predispose them to the development of CDI. PMID- 27193829 TI - Detection and quantification of Aeromonas salmonicida in fish tissue by real-time PCR. AB - Furunculosis, a septicaemic infection caused by the bacterium Aeromonas salmonicida subsp. salmonicida, currently causes problems in Danish seawater rainbow trout production. Detection has mainly been achieved by bacterial culture, but more rapid and sensitive methods are needed. A previously developed real-time PCR assay targeting the plasmid encoded aopP gene of A. salmonicida was, in parallel with culturing, used for the examination of five organs of 40 fish from Danish freshwater and seawater farms. Real-time PCR showed overall a higher frequency of positives than culturing (65% of positive fish by real-time PCR compared to 30% by a culture approach). Also, no real-time PCR-negative samples were found positive by culturing. A. salmonicida was detected by real time PCR, though not by culturing, in freshwater fish showing no signs of furunculosis, indicating possible presence of carrier fish. In seawater fish examined after an outbreak and antibiotics treatment, real-time PCR showed the presence of the bacterium in all examined organs (1-482 genomic units mg-1 ). With a limit of detection of 40 target copies (1-2 genomic units) per reaction, a high reproducibility and an excellent efficiency, the present real-time PCR assay provides a sensitive tool for the detection of A. salmonicida. PMID- 27193831 TI - Aicardi syndrome: when to suspect the unexpected PMID- 27193830 TI - Inverse correlation between longevity and developmental rate among wild C. elegans strains. AB - Genetic studies using model organisms have shown that many long-lived mutants display impaired fitness, such as reduced fecundity and delayed development. However, in several wild animals, the association between longevity and fitness does not seem to be inevitable. Thus, the relationship between longevity and fitness in wild organisms remains inconclusive. Here, we determined the correlation between lifespan and fitness, developmental rate and brood size, by using 16 wild-derived C. elegans strains originated from various geographic areas. We found a negative correlation between lifespan and developmental rate. In contrast, we did not find such negative correlation between longevity and developmental rate among the individuals of C. elegans strains. These data imply that polymorphic genetic variants among wild isolates determine resource allocation to longevity and developmental rate. PMID- 27193832 TI - Treatment of Paget's Disease of Bone with Denosumab: Case Report and Literature Review. AB - Paget's disease is a condition involving focal overactivity of bone cells (osteoblasts and osteoclasts), which can result in significant skeletal morbidity. It is unclear in which bone cells the causative lesion resides. It is managed effectively with potent bisphosphonates, but treatment is difficult if these drugs are contraindicated. We describe a 75-year-old woman with Paget's disease involving the skull who was intolerant of bisphosphonates, so was treated with denosumab. This intervention normalized serum alkaline phosphatase for 4-8 months after each injection and led to some symptomatic improvement. Scintigraphic activity in the lesion was improved but not normalized. We conclude that reduction in RANKL activity by denosumab only partially corrects pagetic activity, indicating that the osteoclast overactivity of Paget's disease is not wholly mediated by RANKL. Denosumab has some clinical utility in Paget's disease and may become a second-line agent in those with contraindications to intravenous bisphosphonates. PMID- 27193834 TI - Enantiodivergent Combination of Natural Product Scaffolds Enabled by Catalytic Enantioselective Cycloaddition. AB - An efficient strategy has been established for the enantiodivergent synthesis of natural product inspired compounds embodying both tropane and pyrrolidine natural product fragments. This strategy includes the enantioselective kinetic resolution of racemic tropanes by means of a copper(I)-catalyzed [3+2] cycloaddition and allows the preparation of two enantiopure products in a one-pot reaction in high yield and with high diastereo- and enantioselectivity by using one chiral catalyst. PMID- 27193833 TI - Suppression of KRas-mutant cancer through the combined inhibition of KRAS with PLK1 and ROCK. AB - No effective targeted therapies exist for cancers with somatic KRAS mutations. Here we develop a synthetic lethal chemical screen in isogenic KRAS-mutant and wild-type cells to identify clinical drug pairs. Our results show that dual inhibition of polo-like kinase 1 and RhoA/Rho kinase (ROCK) leads to the synergistic effects in KRAS-mutant cancers. Microarray analysis reveals that this combinatory inhibition significantly increases transcription and activity of cyclin-dependent kinase inhibitor p21(WAF1/CIP1), leading to specific G2/M phase blockade in KRAS-mutant cells. Overexpression of p21(WAF1/CIP1), either by cDNA transfection or clinical drugs, preferentially impairs the growth of KRAS-mutant cells, suggesting a druggable synthetic lethal interaction between KRAS and p21(WAF1/CIP1). Co-administration of BI-2536 and fasudil either in the LSL KRAS(G12D) mouse model or in a patient tumour explant mouse model of KRAS-mutant lung cancer suppresses tumour growth and significantly prolongs mouse survival, suggesting a strong synergy in vivo and a potential avenue for therapeutic treatment of KRAS-mutant cancers. PMID- 27193835 TI - Species-level core oral bacteriome identified by 16S rRNA pyrosequencing in a healthy young Arab population. AB - BACKGROUND: Reports on the composition of oral bacteriome in Arabs are lacking. In addition, the majority of previous studies on other ethnic groups have been limited by low-resolution taxonomic assignment of next-generation sequencing reads. Furthermore, there has been a conflict about the existence of a 'core' bacteriome. OBJECTIVE: The objective of this study was to characterize the healthy core oral bacteriome in a young Arab population at the species level. METHODS: Oral rinse DNA samples obtained from 12 stringently selected healthy young subjects of Arab origin were pyrosequenced (454's FLX chemistry) for the bacterial 16S V1-V3 hypervariable region at an average depth of 11,500 reads. High-quality, non-chimeric reads >=380 bp were classified to the species level using the recently described, prioritized, multistage assignment algorithm. A core bacteriome was defined as taxa present in at least 11 samples. The Chao2, abundance-based coverage estimator (ACE), and Shannon indices were computed to assess species richness and diversity. RESULTS: Overall, 557 species-level taxa (211+/-42 per subject) were identified, representing 122 genera and 13 phyla. The core bacteriome comprised 55 species-level taxa belonging to 30 genera and 7 phyla, namely Firmicutes, Proteobacteria, Actinobacteria, Bacteroidetes, Fusobacteria, Saccharibacteria, and SR1. The core species constituted between 67 and 87% of the individual bacteriomes. However, the abundances differed by up to three orders of magnitude among the study subjects. On average, Streptococcus mitis, Rothia mucilaginosa, Haemophilus parainfluenzae, Neisseria flavescence/subflava group, Prevotella melaninogenica, and Veillonella parvula group were the most abundant. Streptococcus sp. C300, a taxon never reported in the oral cavity, was identified as a core species. Species richness was estimated at 586 (Chao2) and 614 (ACE) species, whereas diversity (Shannon index) averaged at 3.99. CONCLUSIONS: A species-level core oral bacteriome representing the majority of reads was identified, which can serve as a reference for comparison with oral bacteriomes of other populations as well as those associated with disease. PMID- 27193836 TI - Advanced glycation end products in skin ageing and photoageing: what are the implications for epidermal function? PMID- 27193838 TI - Gender differences in the neural response to acupuncture: clinical implications. AB - OBJECTIVE: To examine gender differences and similarities in the psychophysical and brain responses to acupuncture at GB34, a point that is frequently used to treat motor function issues in Traditional Chinese Medicine. METHODS: Functional MRI (fMRI) was used to measure brain activation in response to acupuncture at GB34 (on the right) in 19 healthy participants (9 male, 10 female). De qi sensations were rated to measure their psychophysical responses. RESULTS: Overall de qi scores did not differ by gender, although females reported greater intensity of aching (p=0.04). Acupuncture activated the hippocampus, thalamus, globus pallidus, caudate body, claustrum, cingulate gyrus, and culmen in males, and the middle and inferior frontal gyrus, precuneus, postcentral gyrus, inferior parietal lobule, superior temporal gyrus, caudate body, insula, fusiform gyrus, cingulate gyrus, amygdala, and parahippocampal gyrus in females. The middle/medial frontal gyrus, middle temporal gyrus, thalamus, globus pallidus, caudate body, uvula, and cerebellar tonsil were activated when data from all subjects were combined. Relative to males, females exhibited greater brain activation in the right-sided postcentral gyrus, precentral gyrus, precuneus, postcentral gyrus, inferior parietal lobule, declive, middle occipital gyrus and parahippocampal gyrus. CONCLUSIONS: The neural effects of GB34 acupuncture might differ between males and females because different brain structures were modulated in response to acupuncture. This potential gender effect should be taken into account in future clinical research. We also revealed that the caudate body was activated by GB34 acupuncture in both males and females and may represent a major target of GB34 acupuncture. TRIAL REGISTRATION NUMBER: KMC IRB 0861-06. PMID- 27193837 TI - The availability of emergency obstetric care in the context of the JSY cash transfer programme in Madhya Pradesh, India. AB - BACKGROUND: Since 2005, India has implemented a national cash transfer programme, the Janani Suraksha Yojana (JSY), which provides women a cash transfer upon giving birth in an existing public facility. This has resulted in a steep rise in facility births across the country. The early years of the programme saw efforts being made to strengthen the ability of facilities to provide obstetric care. Given that the JSY has been able to draw millions of women into facilities to give birth (there have been more than 50 million beneficiaries thus far), it is important to study the ability of these facilities to provide emergency obstetric care (EmOC), as the functionality of these facilities is critical to improved maternal and neonatal outcomes. We studied the availability and level of provision of EmOC signal functions in public facilities implementing the JSY programme in three districts of Madhya Pradesh (MP) state, central India. These are measured against the World Health Report (WHR) 2005benchmarks. As a comparison, we also study the functionality and contribution of private sector facilities to the provision of EmOC in these districts. METHODS: A cross sectional survey of all healthcare facilities offering intrapartum care was conducted between February 2012 and April 2013. The EmOC signal functions performed in each facility were recorded, as were human resource data and birth numbers for each facility. RESULTS: A total of 152 facilities were surveyed of which 118 were JSY programme facilities. Eighty-six percent of childbirths occurred at programme facilities, two thirds of which occurred at facilities that did not meet standards for the provision basic emergency obstetric care. Of the 29 facilities that could perform caesareans, none could perform all the basic EmOC functions. Programme facilities provided few EmOC signal functions apart from parenteral antibiotic or oxytocic administration. Complicated EmOC provision was found predominantly in non-programme (private) facilities; only one of six facilities able to provide such care was in the public sector and therefore in the JSY programme. Only 13 % of all qualified obstetricians practiced at programme facilities. CONCLUSIONS: Given the high proportion of births in public facilities in the state, the JSY programme has an opportunity to contribute to the reduction in maternal and perinatal mortality However, for the programme to have a greater impact on outcomes; EmOC provision must be significantly improved.. While private, non-programme facilities have better human resources and perform caesareans, most women in the state give birth under the JSY programme in the public sector. A demand-side programme such as the JSY will only be effective alongside an adequate supply side (i.e., a facility able to provide EmOC). PMID- 27193839 TI - Using Fluorescence Microscopy to Study Mitosis. AB - Fluorescence microscopy is one of the most important approaches in the cell biologist's toolbox for studying the mitotic spindle. In fact, many of the key insights into our understanding of mitosis have been enabled by the visualization of mitotic processes using fluorescence microscopy. Here, we summarize some of the important considerations for imaging mitosis using fluorescence microscopy. Because light can damage live cells, we emphasize the importance of minimizing cellular damage while obtaining informative images. PMID- 27193840 TI - Using Photoactivatable GFP to Study Microtubule Dynamics and Chromosome Segregation. AB - Mitosis is a highly dynamic process during which the genetic material is equally distributed between two daughter cells. During mitosis, the sister chromatids of replicated chromosomes interact with dynamic microtubules and such interactions lead to stereotypical chromosome movements that eventually result in chromosome segregation and successful cell division. Approaches that allow quantification of microtubule dynamics and chromosome movements are of utmost importance for a mechanistic understanding of mitosis. In this chapter, we describe methods based on activation of photoactivatable green fluorescent protein (PA-GFP) that can be used for quantitative studies of microtubule dynamics and chromosome segregation. PMID- 27193841 TI - Purification and Fluorescent Labeling of Tubulin from Xenopus laevis Egg Extracts. AB - For many years, microtubule research has depended on tubulin purified from cow and pig brains, which may not be ideal for experiments using proteins or extracts from non-brain tissues and cold-blooded organisms. Here, we describe a method to purify functional tubulin from the eggs of the frog, Xenopus laevis. This tubulin has many benefits for the study of microtubules and microtubule based structures assembled in vitro at room temperature. Frog tubulin lacks many of the highly stabilizing posttranslational modifications present in pig brain-derived tubulin, and polymerizes efficiently at room temperature. In addition, fluorescently labeled frog egg tubulin incorporates into meiotic spindles assembled in egg extract more efficiently than brain tubulin, and is thus superior as a probe for Xenopus egg extract experiments. Frog egg tubulin will provide excellent opportunities to identify active nucleation complexes and revisit microtubule polymerization dynamics in vitro. PMID- 27193842 TI - Measuring the Effects of Microtubule-Associated Proteins on Microtubule Dynamics In Vitro. AB - Microtubule dynamic instability, the process by which individual microtubules switch between phases of growth and shrinkage, is essential for establishing the architecture of cellular microtubule structures, such as the mitotic spindle. This switching process is regulated by a complex network of microtubule associated proteins (MAPs), which modulate different aspects of microtubule dynamic behavior. To elucidate the effects of MAPs and their molecular mechanisms of action, in vitro reconstitution approaches with purified components are used. Here, I present methods for measuring individual and combined effects of MAPs on microtubule dynamics, using purified protein components and total-internal reflection fluorescence (TIRF) microscopy. Particular focus is given to the experimental design, proper parameterization, and data analysis. PMID- 27193843 TI - Imaging and Quantifying the Dynamics of gamma-Tubulin at Microtubule Minus Ends in Mitotic Spindles. AB - Understanding the organization of complex microtubule arrays such as the mitotic spindle requires information about the position and dynamics of microtubule plus and minus ends. Whereas plus end dynamics have been widely studied using markers such as EB1-GFP, much less is known about the dynamic properties of minus ends, in part because a suitable marker has only recently become available. Here we describe the use of photoactivatable gamma-tubulin-paGFP to image and quantify the dynamics of microtubule minus ends in mitotic spindles. PMID- 27193845 TI - Encapsulation of Xenopus Egg and Embryo Extract Spindle Assembly Reactions in Synthetic Cell-Like Compartments with Tunable Size. AB - Methods are described for preparing Xenopus laevis egg and embryo cytoplasm and encapsulating extract spindle assembly reactions in cell-like compartments to investigate the effects of cell size on intracellular assembly. Cytoplasm prepared from the eggs or embryos of individual frogs is screened for the ability to form interphase nuclei and metaphase spindles, and subsequently packaged, along with DNA, into droplets of varying size using microfluidics. The dimensions of these cell-like droplets are specified to match the range of cell diameters present in early embryo development. The scaling relationship between droplets and spindles is quantified using live fluorescence imaging on a spinning-disk confocal microscope. By comparing the encapsulated assembly of spindles formed from cytoplasmic extracts prepared from embryos at distinct stages of Xenopus early development, the influence of cell composition and cell size on spindle scaling can be evaluated. Because the extract system is biochemically tractable, the function of individual proteins in spindle scaling can be evaluated by supplementing or depleting factors in the cytoplasm. PMID- 27193844 TI - Visualizing and Analyzing Branching Microtubule Nucleation Using Meiotic Xenopus Egg Extracts and TIRF Microscopy. AB - Mitotic and meiotic spindles consist primarily of microtubules, which originate from centrosomes and within the vicinity of chromatin. Indirect evidence suggested that microtubules also originate throughout the spindle, but the high microtubule density within the spindle precludes the direct observation of this phenomenon. By using meiotic Xenopus laevis egg extract and employing total internal reflection (TIRF) microscopy, microtubule nucleation from preexisting microtubules could be demonstrated and analyzed. Branching microtubule nucleation is an ideal mechanism to assemble and maintain a mitotic spindle, because microtubule numbers are amplified while preserving their polarity. Here, we describe the assays that made these findings possible and the experiments that helped identify the key molecular players involved. PMID- 27193846 TI - In Vitro Kinetochore Assembly. AB - The kinetochore is the primary site of interaction between chromosomes and microtubules of the mitotic spindle during chromosome segregation. Kinetochores are composed of more than 100 proteins that transiently assemble during mitosis at a single epigenetically defined region on each chromosome, known as the centromere. Kinetochore assembly and activity must be tightly regulated to ensure proper microtubule interaction and faithful chromosome segregation. Kinetochore malfunction can result in chromosome segregation defects leading to aneuploidy and cell death. As such, cell free and reconstituted systems to analyze kinetochore formation and function are invaluable in probing the biochemical activities of kinetochores. In vitro approaches to studying kinetochores have enabled the manipulation of kinetochore protein structure, function, interactions, and regulation that are not possible in cells. Here we outline a cell-free approach for the assembly of centromeres and recruitment of functional kinetochores that enables their manipulation and analysis. PMID- 27193847 TI - Biochemical and Structural Analysis of Kinetochore Histone-Fold Complexes. AB - The kinetochore connects chromosomes to microtubules during mitosis and therefore plays an essential role in faithful chromosome segregation. It is built at the centromeric region of the chromosome and is comprised of many protein complexes. CENP-S, -T, -W, and -X are kinetochore components with histone-folds. These proteins play important roles in establishment of kinetochore chromatin. Similar to canonical histones, these kinetochore histone-fold proteins form heteromeric complexes (CENP-S/CENP-X complex and CENP-T/CENP-W complex) and bind DNA in sequence independent manner. In addition, they form a CENP-T-W-S-X heterotetrameric complex and bind DNA in a manner that is different from both CENP-S-X and CENP-T-W. To understand how kinetochores form and function it is necessary to characterize the components in detail. Here, we describe our approaches in purification and characterization of the kinetochore histone-fold complexes. PMID- 27193848 TI - Measuring Kinetochore-Microtubule Attachment Stability in Cultured Cells. AB - Duplicated sister chromatids connect to the mitotic spindle through kinetochores, large proteinaceous structures built at sites of centromeric heterochromatin. Kinetochores are responsible for harnessing the forces generated by microtubule polymerization and depolymerization to power chromosome movements. The fidelity of chromosome segregation relies on proper kinetochore function, as precise regulation of the attachment between kinetochores and microtubules is essential to prevent mitotic errors, which are linked to the initiation and progression of cancer and the formation of birth defects (Godek et al., Nat Rev Mol Cell Biol 16(1):57-64, 2014; Ricke and van Deursen, Semin Cell Dev Biol 22(6):559-565, 2011; Holland and Cleveland, EMBO Rep 13(6):501-514, 2012). Here we describe assays to quantitatively measure kinetochore-microtubule attachment stability in cultured cells. PMID- 27193849 TI - Studying Kinetochores In Vivo Using FLIM-FRET. AB - Kinetochores play essential roles in coordinating mitosis, as a mechanical connector between chromosome and microtubule and as a source of numerous biochemical signals. These mechanical and biochemical behaviors of kinetochores change dynamically in cells during mitosis. Therefore, understanding kinetochore function requires an imaging tool that quantifies the protein-protein interactions or biochemical changes with high spatiotemporal resolution. FRET has previously been used in combination with biosensors to probe protein-protein interactions and biochemical activity. In this chapter, we introduce FLIM-FRET, a lifetime-based method that quantifies FRET, and describe the use of FLIM-FRET as a method for studying dynamic kinetochore behavior in cells with high spatiotemporal resolution. PMID- 27193850 TI - Purification of Fluorescently Labeled Saccharomyces cerevisiae Spindle Pole Bodies. AB - Centrosomes are components of the mitotic spindle responsible for organizing microtubules and establishing a bipolar spindle for accurate chromosome segregation. In budding yeast, Saccharomyces cerevisiae, the centrosome is called the spindle pole body, a highly organized trilaminar structure embedded in the nuclear envelope. Here we describe a detailed protocol for the purification of fluorescently labeled spindle pole bodes from S. cerevisiae. Spindle pole bodies are purified from yeast using a TAP-tag purification followed by velocity sedimentation.This highly reproducible TAP-tag purification method improves upon previous techniques and expands the scope of in vitro characterization of yeast spindle pole bodies. The genetic flexibility of this technique allows for the study of spindle pole body mutants as well as the study of spindle pole bodies during different stages of the cell cycle. The ease and reproducibility of the technique make it possible to study spindle pole bodies using a variety of biochemical, biophysical, and microscopic techniques. PMID- 27193852 TI - Assays to Study Mitotic Centrosome and Spindle Pole Assembly and Regulation. AB - Faithful chromosome segregation during cell division requires proper bipolar spindle assembly and critically depends on spindle pole integrity. In most animal cells, spindle poles form as the result of the concerted action of various factors operating in two independent pathways of microtubule assembly mediated by chromatin/RanGTP and by centrosomes. Mutation or deregulation of a number of spindle pole-organizing proteins has been linked to human diseases, including cancer and microcephaly. Our knowledge on how the spindle pole-organizing factors function at the molecular level and cooperate with one another is still quite limited. As the list of these factors expands, so does the need for the development of experimental approaches to study their function. Cell-free extracts from Xenopus laevis eggs have played an instrumental role in the dissection of the mechanisms of bipolar spindle assembly and have recently allowed the reconstitution of the key steps of the centrosome-driven microtubule nucleation pathway (Joukov et al., Mol Cell 55:578-591, 2014). Here we describe assays to study both centrosome-dependent and centrosome-independent spindle pole formation in Xenopus egg extracts. We also provide experimental procedures for the use of artificial centrosomes, such as microbeads coated with an anti-Aurora A antibody or a recombinant fragment of the Cep192 protein, to model and study centrosome maturation in egg extract. In addition, we detail the protocol for a microtubule regrowth assay that allows assessment of the centrosome-driven spindle microtubule assembly in mammalian cells. PMID- 27193853 TI - Analyzing Spindle Positioning Dynamics in Cultured Cells. AB - As spindle positioning during mitosis is a highly dynamic process, live cell imaging is a key technology when studying its underlying mechanisms. Recent advances in imaging tools and microscope systems have enabled us to simultaneously visualize several cellular components in living cells with high temporal and spatial resolution. By combining live cell imaging with functional assays such as RNAi-based depletions, drug inhibition, and micropatterned coverslips, novel and unexpected mechanisms of spindle positioning have been uncovered. In this chapter, I present methods for analyzing the dynamics of spindle positioning in cultured cells. PMID- 27193851 TI - A Cell-Free System for Real-Time Analyses of Centriole Disengagement and Centriole-to-Centrosome Conversion. AB - Centriole or centrosome number in cycling cells is strictly maintained through coordinated duplication and segregation. Duplication is limited to once only per cell cycle by separating the assembly event that occurs in S/G2 phase from the two licensing events, centriole disengagement and centriole-to-centrosome conversion, both of which occurs in mitosis. In addition to duplication licensing, centriole-to-centrosome conversion also enables centrioles to associate with spindle poles and thereby to segregate equally during cell division. Centriole disengagement and centriole-to-centrosome conversion thus constitute the major regulatory module ensuring centrosome homeostasis in cycling cells. Using Xenopus egg extracts and purified engaged centrioles, we here describe an in vitro assay allowing us to synchronously induce the initiation of centriole disengagement and centrosome formation, pause the reaction anytime during the process, and more importantly, preserve "reaction intermediates" for further analyses. PMID- 27193854 TI - Quantification of Mitotic Chromosome Alignment. AB - The alignment of chromosomes during metaphase is a hallmark of mitosis. For this reason, chromosome alignment has served as an informative functional assay for evaluating mitotic fidelity. The common approach of quantifying the number of mitotic cells with unaligned chromosomes within a population has led to the identification of many proteins required for this conserved process. However, more sensitive assays are now required to dissect the complex molecular control of chromosome alignment. In this chapter, we describe a microscopy-based method for objectively quantifying the distribution of fluorescently labeled chromosomes within the mitotic spindle that can be used to evaluate the extent of chromosome alignment within individual mitotic cells. PMID- 27193855 TI - Imaging Mitosis in the Moss Physcomitrella patens. AB - At first glance, mitosis in plants looks quite different from that in animals. In fact, terrestrial plants have lost the centrosome during evolution, and the mitotic spindle is assembled independently of a strong microtubule organizing center. The phragmoplast is a plant-specific mitotic apparatus formed after anaphase, which expands centrifugally towards the cell cortex. However, the extent to which plant mitosis differs from that of animals at the level of the protein repertoire is uncertain, largely because of the difficulty in the identification and in vivo characterization of mitotic genes of plants. Here, we discuss protocols for mitosis imaging that can be combined with endogenous green fluorescent protein (GFP) tagging or conditional RNA interference (RNAi) in the moss Physcomitrella patens, which is an emergent model plant for cell and developmental biology. This system has potential for use in the high-throughput study of mitosis and other intracellular processes, as is being done with various animal cell lines. PMID- 27193856 TI - Small Molecule Approach to Study the Function of Mitotic Kinesins. AB - Mitotic motor proteins of the kinesin superfamily are critical for the faithful segregation of chromosomes and the formation of the two daughter cells during meiotic and mitotic M-phase. Of the 45 human kinesins, roughly a dozen are involved in the assembly of the bipolar spindle, alignment of chromosomes at the spindle equator, chromosome segregation, and cytokinesis. The functions of kinesins in these processes are highly diverse and include the transport of cargo molecules, sliding and bundling of microtubules, and regulation of microtubule dynamics. In light of this multitude of diverse functions and the complex functional interplay of different kinesins during M-phase, it is not surprising that one of the greatest challenges in cell biology is the functional dissection of individual motor proteins. Reversible and fast acting small molecules are powerful tools to accomplish this challenge. However, the validity of conclusions drawn from small molecule studies strictly depends on compound specificity. In this chapter, we present methods for the identification of small molecule inhibitors of a motor protein of interest. In particular, we focus on a protein based large throughput screen to identify inhibitors of the ATPase activity of kinesins. Furthermore, we provide protocols and guidelines for secondary screens to validate hits and select for specific inhibitors. PMID- 27193858 TI - Probing Mitosis by Manipulating the Interactions of Mitotic Regulator Proteins Using Rapamycin-Inducible Dimerization. AB - Inducible dimerization is a general approach to experimentally manipulate protein protein interactions with temporal control. This chapter describes the use of rapamycin-inducible dimerization to manipulate mitotic regulatory proteins, for example to control kinetochore localization. A significant feature of this method relative to previously described protocols is the depletion of endogenous FKBP12 protein, which markedly improves dimerization efficiency. PMID- 27193857 TI - Identification and Characterization of Mitotic Spindle-Localized Transcripts. AB - RNAs associate with the mitotic spindle in a variety of organisms, where they can spatially regulate protein production, ensure their proper segregation during cell division, or perform translation-independent roles in spindle formation. The identification of spindle-associated RNAs is an important first step in understanding the biological consequences of this phenomenon. In this chapter, we describe a method to use Xenopus laevis egg extracts to assemble and isolate mitotic spindles and to identify the spindle-associated RNAs. The method described here can be used in combination with immunodepletions, the addition of inhibitors, or other perturbations to investigate factors that affect RNA localization to the spindle. Finally, we describe a method to assess the consequences of ablating RNA in the extract on spindle formation. PMID- 27193859 TI - Studying Kinetochore Kinases. AB - Mitotic kinetochores are signaling network hubs that regulate chromosome movements, attachment error-correction, and the spindle assembly checkpoint. Key switches in these networks are kinases and phosphatases that enable rapid responses to changing conditions. Describing the mechanisms and dynamics of their localized activation and deactivation is therefore instrumental for understanding the spatiotemporal control of chromosome segregation. PMID- 27193860 TI - Engineering and Functional Analysis of Mitotic Kinases Through Chemical Genetics. AB - During mitosis, multiple protein kinases transform the cytoskeleton and chromosomes into new and highly dynamic structures that mediate the faithful transmission of genetic information and cell division. However, the large number and strong conservation of mammalian kinases in general pose significant obstacles to interrogating them with small molecules, due to the difficulty in identifying and validating those which are truly selective. To overcome this problem, a steric complementation strategy has been developed, in which a bulky "gatekeeper" residue within the active site of the kinase of interest is replaced with a smaller amino acid, such as glycine or alanine. The enlarged catalytic pocket can then be targeted in an allele-specific manner with bulky purine analogs. This strategy provides a general framework for dissecting kinase function with high selectivity, rapid kinetics, and reversibility. In this chapter we discuss the principles and techniques needed to implement this chemical genetic approach in mammalian cells. PMID- 27193861 TI - Using Cell Culture Models of Centrosome Amplification to Study Centrosome Clustering in Cancer. AB - The link between centrosome amplification and cancer has been recognized for more than a century, raising many key questions about the biology of both normal and cancer cells. In particular, the presence of extra centrosomes imposes a great challenge to a dividing cell by increasing the likelihood of catastrophic multipolar divisions. Only recently have we begun to understand how cancer cells successfully divide by clustering their extra centrosomes for bipolar division. Several hurdles to dissecting centrosome clustering include limitations in the methodologies used to quantify centrosome amplification, and the lack of appropriate cell culture models. Here, we describe how to accurately assess centrosome number and create isogenic cell lines with or without centrosome amplification. We then describe how imaging of cell division in these cell culture models leads to identification of the molecular machinery uniquely required for cells with extra centrosomes. These approaches have led to the identification of molecular targets for selective cancer therapeutics that can kill cancer cells with extra centrosomes without affecting normal cells with two centrosomes. We further anticipate that the approaches described here will be broadly applicable for studying the causes and consequences of centrosome amplification in a variety of contexts across cancer pathophysiology, such as cell migration and metastasis. PMID- 27193862 TI - Generation and Purification of Tetraploid Cells. AB - Tetraploid cells are genetically unstable and have the capacity to promote the development and/or progression of human malignancies. It is now estimated that ~40 % of all solid tumors have passed through a tetraploid intermediate stage at some point during their development. Understanding the biological characteristics of tetraploid cells that impart oncogenic properties is therefore a highly relevant and fundamentally important aspect of cancer biology. Here, we describe strategies to efficiently generate and purify tetraploid cells for use in cell biological studies. PMID- 27193864 TI - A Neuropsychologist's Guide To Undertaking a Systematic Review for Publication: Making the most of PRISMA Guidelines. AB - There is increasing impetus to improve the quality of research and scientific writing. Systematic reviews provide Class 1 research evidence, are based upon an established rigor and communicate results in a comprehensive manner, and are therefore particularly relevant to clinicians and researchers. Clinician requirements for quality systematic reviews are twofold: to keep up to date with research and to make informed decisions including those required for diagnoses, disease or risk assessment, and treatment. Researchers rely upon quality systematic reviews to compete for diminishing research funds, prove efficacy for intervention trials, and to meet increasing demand for evidence based intervention. However, insufficient systematic reviews are undertaken, and the methodological rigor and quality are often variable. The aim of this article is to guide researchers through the iterative systematic review process in order to improve quality and thereby increase publication rates. The step by step guide provides a road map through the EQUATOR network and practical suggestions in order to meet the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) (Moher et al. 2009) as well as encouraging high standards through the use of quality rating scales. Lastly, information is provided to encourage quantitative analysis to improve the synthesis of results and qualitative interpretation, such as calculating effect sizes or conducting a meta-analyses as the ultimate goal of a systematic review. PMID- 27193865 TI - Acetohydrazone: A Transient Directing Group for Arylation of Unactivated C(sp(3)) H Bonds. AB - A straightforward and efficient method has been developed for the synthesis of 2 benzylbenzaldehyde derivatives from 2-methylbenzaldehyde and iodobenzene via a C(sp(3))-H activation process. In the course of the activation reaction, acetohydrazone is formed between 2-benzylbenzaldehyde and acetohydrazine as a transient directing group. As a new kind of transient directing group, acetohydrazone exhibits a remarkable directing effect to give corresponding products in good to excellent yields. PMID- 27193863 TI - Anti-Microtubule Drugs. AB - Small molecule drugs that target microtubules (MTs), many of them natural products, have long been important tools in the MT field. Indeed, tubulin (Tb) was discovered, in part, as the protein binding partner of colchicine. Several anti-MT drug classes also have important medical uses, notably colchicine, which is used to treat gout, familial Mediterranean fever (FMF), and pericarditis, and the vinca alkaloids and taxanes, which are used to treat cancer. Anti-MT drugs have in common that they bind specifically to Tb in the dimer, MT or some other form. However, their effects on polymerization dynamics and on the human body differ markedly. Here we briefly review the most-studied molecules, and comment on their uses in basic research and medicine. Our focus is on practical applications of different anti-MT drugs in the laboratory, and key points that users should be aware of when designing experiments. We also touch on interesting unsolved problems, particularly in the area of medical applications. In our opinion, the mechanism by which any MT drug cures or treats any disease is still unsolved, despite decades of research. Solving this problem for particular drug disease combinations might open new uses for old drugs, or provide insights into novel routes for treatment. PMID- 27193866 TI - Freeze-drying of "pearl milk tea": A general strategy for controllable synthesis of porous materials. AB - Porous materials have been widely used in many fields, but the large-scale synthesis of materials with controlled pore sizes, pore volumes, and wall thicknesses remains a considerable challenge. Thus, the controllable synthesis of porous materials is of key general importance. Herein, we demonstrate the "pearl milk tea" freeze-drying method to form porous materials with controllable pore characteristics, which is realized by rapidly freezing the uniformly distributed template-containing precursor solution, followed by freeze-drying and suitable calcination. This general and convenient method has been successfully applied to synthesize various porous phosphate and oxide materials using different templates. The method is promising for the development of tunable porous materials for numerous applications of energy, environment, and catalysis, etc. PMID- 27193867 TI - Oxygen diffusion in ThO2-CeO2 and ThO2-UO2 solid solutions from atomistic calculations. AB - We elucidate oxygen diffusivity in ThO2-CeO2 and ThO2-UO2 solid solutions across their whole concentration ranges in the phase diagram using static pair-potential calculations and molecular dynamics simulations. Between pure CeO2 (and UO2) and pure ThO2, oxygen diffusivity is higher in CeO2 (and UO2) due to lower oxygen migration barriers. With the addition of Th to CeO2 (and UO2) in the phase diagram, the diffusivity decreases due to the increase in the migration barriers introduced by a larger ionic radius of Th. On the other side of the phase diagram, with the addition of Ce to ThO2 oxygen diffusion decreases due to oxygen vacancy binding with Ce, even though the migration barriers decrease due to the smaller size of Ce than the host Th. Using these calculations, we provide a schematic of high oxygen diffusivity regions in the phase diagram. We also compare the impact of tetravalent dopants (e.g. actinides) on oxygen vacancy energetics to that of trivalent dopants (e.g. lanthanides). We find that trivalent dopants bind much more strongly with oxygen vacancy than the tetravalent dopants. We also find that the tetravalent dopants that have larger radii than the host cation have negative oxygen vacancy binding energy, whereas all trivalent dopants have positive binding energy irrespective of their ionic radii. This work thus highlights key differences in the oxygen vacancy energetics between the trivalent and tetravalent cations. PMID- 27193868 TI - Synthesis and application of thiol-functionalized magnetic nanoparticles for studying interactions of epirubicin hydrochloride with bovine serum albumin by fluorescence spectrometry. AB - A novel method was developed for studying the interaction between epirubicin hydrochloride (EPI) and bovine serum albumin (BSA) by fluorescence spectrometry. Fe3 O4 magnetic nanoparticles (MNPs) synthesized and functionalized with thiol group were employed for the immobilization and separation of target BSA in reaction solutions. The concentrations of the non-immobilized BSA and unbound EPI were obtained separately by fluorescence spectrometry. The binding constants (Ka ) and number of binding sites (n) of EPI with BSA were calculated. In this study, the Ka value was 5.05 * 105 L mol-1 , suggesting a strong binding of EPI to BSA, and the n value was 1.15. The effects of common metal ions on Ka of EPI with BSA were also investigated, and the results showed there was clearly bindings between the metal ions and BSA. The precise binding sites of EPI on BSA were determined as being in site I from the competitive displacement experiments. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27193871 TI - Two novel selenidostannates from mixed structure-directing systems: the large ten membered ring of [Sn3Se4] semicubes and the 3D [Sn4Se9]n(2n-) with multi channels. AB - Ionothermal syntheses, characterization and properties of two selenidostannate compounds with two- or three-dimensional (D) skeletons by utilizing the synergistic structure-directing effects of the ionic liquid (IL) [Bmmim]Cl (Bmmim = 1-butyl-2,3-dimethylimidazolium) and in-situ generated metal-amine complexes (MACs), namely, 2D-(Bmmim)2[Ni(teta)(en)][Sn3Se7]2 (1, teta = triethylenetetramine, en = ethylenediamine) and 3D (Bmmim)1.5(dienH)0.5Ni(dien)2[Sn4Se9]2 (2, dien = diethylenetriamine) are presented. Single-crystal X-ray diffraction analyses revealed that compound 1 possesses a lamellar anionic [Sn3Se7]n(2n-) structure comprising a large ten membered ring with a window size of 24.85 * 13.38 A when considering the [Sn3Se4] semicube as a member. While 2 features a 3D [Sn4Se9]n(2n-) framework with orthogonally intersecting channels where the three different types of cations are filled. The successful isolation of these two compounds demonstrated again that the mixed SDA strategy is promising for the synthesis of novel crystalline selenidostannates. PMID- 27193870 TI - Breaking Barriers to Effective Type 2 Diabetes Management: Findings from the use of the OPTIMA(c) Questionnaire in Clinical Practice. AB - BACKGROUND: The OPTIMA(c) (MSD, Courbevoie, France) questionnaire was developed to promote shared decisions and the set-up of specific micro-objectives in clinical practice by optimizing communication between type 2 diabetes (T2DM) patients and their physicians. The present study aimed to assess OPTIMA in clinical practice. METHODS: A cross-sectional multicenter observational study was conducted in France from 2012 to 2014. During routine consultation, patients completed one of the five modules of the OPTIMA questionnaire (Physical activity, Diet, Treatment, Knowledge of the disease or Self-monitoring of blood glucose). The rate of SMART (specific, measurable, acceptable, realistic, timely) micro objective set-up following the use of the questionnaire was assessed. Data on how patients felt about their diabetes management (beliefs concerning actions, how easy they were to do and how often they were done in practice) were gathered. Finally, patients' and physicians' opinions on OPTIMA were assessed using the PRAgmatic Content and face validity Test (PRAC-Test(c) (Mapi, Lyon, France) evaluation questionnaire. RESULTS: Overall, 807 patients were included by 186 physicians. While 92.7 % of consultations led to the set-up of a micro-objective, only 22.3 % were SMART micro-objectives: Physical activity module (34.3 %), Diet module (9.6 %), Treatment module (16.4 %), Knowledge of the disease module (25.2 %), and self-monitoring of blood glucose module (29.5 %). Among patients completing the Physical activity module, 79.0 % reported that they believed physical activity was useful, 35.0 % that it was easy, and 25.8 % that they regularly practised it. PRAC-Test results showed that OPTIMA was a useful and easy-to-use questionnaire that promotes communication between physicians and their patients according to 92.8 % of patients and 69.4 % of physicians. CONCLUSION: The OPTIMA questionnaire facilitates communication between patients and their physicians and promotes the set-up of micro-objectives concerning T2DM management. The Physical activity module was the most likely of the five modules in the questionnaire to lead to the set-up of SMART micro-objectives. FUNDING: MSD France. PMID- 27193869 TI - Integrative microbial community analysis reveals full-scale enhanced biological phosphorus removal under tropical conditions. AB - Management of phosphorus discharge from human waste is essential for the control of eutrophication in surface waters. Enhanced biological phosphorus removal (EBPR) is a sustainable, efficient way of removing phosphorus from waste water without employing chemical precipitation, but is assumed unachievable in tropical temperatures due to conditions that favour glycogen accumulating organisms (GAOs) over polyphosphate accumulating organisms (PAOs). Here, we show these assumptions are unfounded by studying comparative community dynamics in a full-scale plant following systematic perturbation of operational conditions, which modified community abundance, function and physicochemical state. A statistically significant increase in the relative abundance of the PAO Accumulibacter was associated with improved EBPR activity. GAO relative abundance also increased, challenging the assumption of competition. An Accumulibacter bin-genome was identified from a whole community metagenomic survey, and comparative analysis against extant Accumulibacter genomes suggests a close relationship to Type II. Analysis of the associated metatranscriptome data revealed that genes encoding proteins involved in the tricarboxylic acid cycle and glycolysis pathways were highly expressed, consistent with metabolic modelling results. Our findings show that tropical EBPR is indeed possible, highlight the translational potential of studying competition dynamics in full-scale waste water communities and carry implications for plant design in tropical regions. PMID- 27193872 TI - Knockdown of COUP-TFII inhibits cell proliferation and induces apoptosis through upregulating BRCA1 in renal cell carcinoma cells. AB - COUP-TFII belongs to the nuclear receptor family, which is highly expressed in many kinds of tumors. Previous studies have shown that COUP-TFII can promote tumor progression through regulating tumor angiogenesis and cell proliferation and migration of certain cancer cells. However, the function of COUP-TFII in renal cell carcinoma (RCC) is not clear. Here, we showed that clinical RCC tumor tissues showed much higher COUP-TFII expression level than adjacent normal tissues. When COUP-TFII was knocked down in RCC 769-P and 786-O cells by siRNA or shRNA-expressing lentivirus, the cell proliferation was markedly inhibited, and apoptosis increased. Moreover, the tumor growth of COUP-TFII knockdown 769-P and 786-O xenografts in nude mice was also obviously inhibited. Using qRT-PCR and Western blot, we showed that the expression of the tumor suppressor gene BRCA1 was upregulated in COUP-TFII knockdown cells. Simultaneously knockdown of BRCA1 and COUP-TFII partially rescued the inhibited cell proliferation and increased apoptosis in COUP-TFII single knockdown cells. These results indicate that COUP TFII may play an oncogenic role in RCC, and COUP-TFII may promote tumor progression through inhibiting BRCA1. PMID- 27193873 TI - Plasma apelin level in patients with restless legs syndrome and its association with periodic leg movements. AB - OBJECTIVES: Apelin is an antioxidant and anti-inflammatory molecule secreted by adipose tissue and has a protective effect on cardiac and neuronal tissue. Recent studies have reported that the risk of vascular disease is increased in restless legs syndrome (RLS). We aimed to measure plasma levels of apelin in patients with RLS. Additionally, we wanted to determine if there is any relationship between apelin levels and RLS disease severity and the periodic leg movement index (PLMI). METHOD: A total of 14 RLS patients with moderate-to-severe symptoms and 14 age- and body mass index (BMI)-matched healthy controls participated in the study. All participants had no concomitant medical disorder nor took medications. The international RLS rating scale (IRLSS) was used to determine disease severity. Polysomnography (PSG) served to exclude other sleep disorders such as sleep-related breathing disorders and to measure sleep parameters. RESULTS: The mean plasma apelin level was significantly lower in the patient group compared to the control group independent of IRLSS score and PSG findings (p = 0.004). After comparison between the RLS patient group and control group, the patient group was divided into two subgroups based on a PLMI above or below 15 events per hour. A reduced mean apelin level was observed in the patient group having a PLMI above 15 compared to the patient group with PLMI below 15 and the control group (p = 0.003). There was no correlation between plasma apelin levels and disease severity and PLMI in the two patient subgroups. CONCLUSIONS: RLS patients especially those with a PLMI above 15 have low plasma apelin levels independent of disease severity and sleep parameters such as sleep duration and quality. Decreased apelin levels may explain the increased risk for vascular diseases in those patients. PMID- 27193874 TI - Localization of the high-resolution area in the ganglion cell layer of the Baikal seal Pusa sibirica Gm.1788. AB - The morphological and functional density of the retinal ganglion cells of the Baikal Lake endemic seal Pusa sibirica was studied using cresyl-violet-stained whole-mounts. An area of the highest concentration of ganglion cells has been identified by drawing up a density map. This was an ellipsoid spot in the upper temporal part of the retina 6-7 mm from the visual nerve output. The maximum cell density in this area was 3800 cells/mm(2). The retinal resolution estimated from the maximum density of ganglion cells and the posterior nodal distance (24 mm) was 2.4' in the water and 3' in the air, and this can be used as an estimation of the retina resolving power. PMID- 27193875 TI - Effect of chronic fluoxetine treatment on audiogenic epilepsy, symptoms of anxiety and depression in rats of four lines. AB - Anxiety (Anx) and depression (Dp) levels were evaluated in rats of 4 lines: 2 of them (KM and "4") exhibited audiogenic seizures (AS), and 2 (Wistar and "0") had no AS. In KM rats (with AS), Anx and Dp levels were higher than in Wistars (without AS), while in "4" and "0" rats with the related genetic background but contrasting in AS severity, Anx and Dp indices were not different. Fluoxetine treatment exerted antidepressant effect in all rat lines irrespective of its effect on AS. Thus, phenotypic expression of AS is not directly associated with the mechanisms of Anx and Dp development. PMID- 27193876 TI - Polymorphism and preadaptation of horses (Equus) of the mountains surrounding Lake Baikal in Pleistocene. AB - The first data on polymorphism and preadaptation of the Pleistocene horses in the mountains surrounding Lake Baikal are presented. It has been shown that disregard of intraspecific polymorphism leads to unreasonable ignoring of their diversity, phylogenetically false constructions, and incorrect interpretation of natural environment. PMID- 27193877 TI - The effect of bloom of filamentous green algae on the reproduction of yellowfin sculpin Cottocomephorus grewingkii (Dybowski, 1874) (Cottoidae) during ecological crisis in Lake Baikal. AB - In shallow water areas of open Lake Baikal, filamentous green alga of the genus Spirogyra grows abundantly. Together with alga of the genus Ulothrix, it forms algal mats. According to our observations from 2010 to 2013, the spawning habitat conditions for the yellowfin sculpin Cottocomephorus grewingkii (Dybowski, 1874) (Cottidae) proved to be significantly disturbed in the littoral zone of Listvennichnyi Bay (southern Baikal), which, in turn, reduced the number of egg layings. With a 100% projective cover of the floor and a high density of green filamentous algae, the shallow-water stony substrate becomes completely inaccessible for spawning of the August population. PMID- 27193878 TI - Development of nanostructured phosphorite: Study of the safety of application. AB - A nanostructured mineral food supplement with a particle size of 60.0-120.0 nm was manufactured from phosphorite by ultrasonic dispersion. It was found that intragastric administration of nanostructures phosphorite to mice is relatively safe: clinical signs of intoxication appeared after a single administration of the preparation only at a dose of 90 mg/kg; a dose of 150 mg/kg caused death of 8% of mice, in which injuries of organs of the gastrointestinal tract were observed. When the preparation was administered subcutaneously, intramuscularly, or intraperitoneally, small phosphorite conglomerates and inflammation of the surrounding tissues and organs were observed at the injection site. Death of 25% of animals was observed in the group of mice which received intraperitoneal injections of nanophosphorite at a dose of 200 mg/kg. PMID- 27193880 TI - Viviparity of larvae, a new type of development in phoronids (Lophophorata: Phoronida). AB - A new type of phoronid development, viviparity of larvae, has been discovered in a new phoronid species that lives as a commensal of digging sand shrimps in Vostok Bay, the Sea of Japan. The embryos develop in the mother's trunk coelom up to the young larva stage. During development, embryos increase in size twice and probably obtain nutriment from the mother's coelomic fluid. Spawning occurs by young larvae, which are released through nephridiopores. The new type of development is described in a phoronid that has a small body size but a high fertility, producing large amounts of extremely small eggs. The combination of viviparity and large number of eggs increases the number of competent larvae that can undergo metamorphosis in the burrows of shrimps. PMID- 27193881 TI - Architectonics of the hair of sled dogs of Chukotka. AB - Architectonics of guard hairs from dogs of recent breeds, mongrel sled dogs, and fossil dogs from ancient settlements of Chukotka have been investigated using scanning electron microscopy. Distinct features of hair structure important for adaptation, including the adaptation to harness in sled dogs, were identified. Hairs of Chukchi sled dogs were most similar to those of the fossil dogs. PMID- 27193879 TI - Changes in the contents of strontium, barium, and lead in scales of bream Abramis brama from the Mozhaisk Reservoir over a quarter century. AB - The heavy metal contents in the scales of bream (Abramis brama) from the Mozhaisk Reservoir collected in the second half of the 1980s were compared to the current values. The concentrations of three out of the seven elements studied in the bream scales have changed severalfold during the past quarter century: that of strontium has decreased, and those of barium and lead have increased. Short-term variations of heavy metal contents have proved to be smaller than the observed long-term differences. There is grounds to believe that these long-term differences adequately reflect the changes that have occurred in the water body. PMID- 27193882 TI - Viscoelastic features of adhesive setae of the tokay gecko (Gekko gecko L.). AB - Deformations of particular setae of adhesive toe pad of the tokay gecko were investigated by atomic-force microscopy. The effective elastic modulus of the investigated setae varying within 0.34-19 GPa, a pronounced hysteresis was observed during reversible bending of setae. The hysteresis-related energy losses may be as high as 98% of the total bending work. The pronounced viscous features of the setae contradict the hypothesis of dynamic self-cleaning of the gecko adhesive cover, according to which the setae are considered as absolutely elastic cantilever beams. PMID- 27193883 TI - Progenesis in the evolution of the nudibranch mollusks genus Dendronotus (Gastropoda: Nudibranchia). AB - The morphology and postlarval ontogenesis of the radula in 11 species of the genus Dendronotus Alder et Hancock, 1845, has been studied. Four types of radula are recognized in adult mollusks. Proposed evidence suggests that small species of Dendronotus have evolved by progenesis. PMID- 27193884 TI - New data on the internal organs of a frozen Yukagir bison mummy (Bison priscus Bojanus, 1827), Yakutia, Russia. AB - The paper presents the first morphological description of the internal organs of a frozen corpse of the steppe bison Bison priscus (Bojanus, 1827) from the Holocene of northern Yakutia. Necropsy revealed that most of the internal organs, including the brain, heart with the main vessels, and reproductive system were well preserved. It demonstrated that the anatomy of this bison was close to that of the genera Bos and Bison. Trauma or pathological changes in the organs were not detected. The cause of death of the bison remains unknown. PMID- 27193885 TI - Cytokine-producing function of human blood cells in chronic atrophic gastritis and gastric adenomas and adenocarcinomas. AB - The cytokine-producing potential of blood cells has been studied in the atrophic gastritis-adenoma-adenocarcinoma progression of pathological states of the stomach. It has been revealed that, at the initial stage of carcinogenesis, namely adenoma, immunocompetent cells have the highest cytokine-producing proto oncogenic potential as compared to both atrophic gastritis, which presents a precancerous condition, and completely formed malignant tumor (gastric adenocarcinoma). PMID- 27193887 TI - Controlled Penetration of a Novel Dimeric Ceramide into and across the Stratum Corneum Using Microemulsions and Various Types of Semisolid Formulations. AB - Ceramides (CERs) are integral parts of the intercellular lipid lamellae of the stratum corneum (SC), which is responsible for the barrier function of the skin. Many skin diseases such as atopic dermatitis and psoriasis are associated with the depletion or disturbance of the level of CERs in the SC. Administration of an exogenous novel dimeric ceramide (dCER) deep into the SC may help to stabilize the SC barrier substantially and to treat some skin disease conditions. Consequently, with the help of the existing technology, it might be possible to formulate various pharmaceutical dosage forms that can facilitate penetration of dCER into the SC. Therefore, the penetration of dCER was studied using a high performance liquid chromatography/atmospheric-pressure ionization/mass spectrometry method for the detection and quantification of exogenous dCER in the SC as well as other skin layers. Penetration studies were carried out in the Franz diffusion cell using excised human skin ex vivo. Penetration of dCER was studied with 3 model formulations: a colloidal formulation (microemulsion), a cream formulation with ethoxydiglycol as penetration enhancer and a nanoformulation. The highest concentrations of dCER in the different skin layers were found after application of the cream with penetration enhancer. Surprisingly, the lowest concentrations of dCER in the different skin layers were found after application of the microemulsion. PMID- 27193886 TI - Incidence and correlated factors of beta cell failure in a 4-year follow-up of patients with type 2 diabetes: a longitudinal analysis of the BETADECLINE study. AB - AIMS: Type 2 diabetes is associated with progressive deterioration of beta cell function and loss of glycemic control, with increased morbidity and mortality from microvascular and macrovascular complications. Factors predictive of beta cell decline are needed. METHODS: We have conducted a prospective evaluation of baseline predictors of beta cell dysfunction and insulin initiation in a cohort of outpatients with type 2 diabetes receiving stable treatment with oral hypoglycemic agents or dietary intervention, over a 4-year follow-up period. RESULTS: Of 507 patients enrolled, 56 (10.8 %) experienced the study endpoint of initiation of insulin therapy. Univariate and multivariate Cox proportional hazard regression analyses revealed that the likelihood of initiating insulin therapy during follow-up increased with longer diabetes duration and with higher baseline values for hemoglobin A1c, fasting plasma glucose, triglycerides, proinsulin, interleukin-6, Homeostatic Model Assessment-IR and lower values for Homeostatic Model Assessment-B. The likelihood of initiating insulin therapy increased by 46 % for each 1 % increase (10.9 mmol/mol) in baseline hemoglobin A1c and by 6 % for each unit increase (1 ng/l) in baseline IL-6 level. The risk was fourfold higher in the lowest versus highest Homeostatic Model Assessment-B quartile. Treatment with metformin plus a secretagogue increased the risk by fourfold. CONCLUSIONS: Our results show that commonly measured parameters may predict treatment failure in type 2 diabetes and suggest that early treatment with metformin plus secretagogues may foretell this failure. PMID- 27193888 TI - When dermoscopy is supported by Tzanck smear. PMID- 27193889 TI - The algorithm for Alzheimer risk assessment based on APOE promoter polymorphisms. AB - BACKGROUND: Over the past two decades, the APOE gene and its polymorphisms have been among the most studied risk factors of Alzheimer disease (AD) development; yet, there are discrepancies between various studies regarding their impact. For this reason, the evaluation of the APOE genotype has not been included in the current European Federation of Neurological Societies guidelines for AD diagnosis and management. This aim of this study was to add to this discussion by assessing the possible influence of multiple polymorphisms in the promoter region of the APOE gene and genotypes of its allele E on the risk for dementia. METHODS: We performed a comprehensive analysis of APOE gene polymorphisms, assessed the detected genotypes and correlated molecular findings with serum apolipoprotein E concentrations. The study comprised 110 patients with AD and 110 age-matched healthy individuals from the Polish population. RESULTS: Four polymorphisms of the APOE gene had minor allele frequency exceeding 5% and were included in the analysis: -491A/T (rs449647), -427T/C (rs769446), -219T/G (rs405509) in the promoter region and +113G/C (rs440446) in intron 1. A protective effect of the 219G allele on AD development was observed. Also, the -491T and -219G alleles were found to be underrepresented in the carriers of the APOE E4 variant. On the basis of the genotype and linkage disequilibrium studies, a relative score was attributed to given genotypes with respect to the estimated probability of their protective effects against AD, giving rise to the 'preventive score'. This 'preventive score', based on the total sums of the relative scores, expresses the protective effect deriving from the synergistic action of individual single nucleotide polymorphisms. The 'preventive score' was identified as an independent predictive factor. CONCLUSIONS: We propose a novel, more complex approach to AD risk assessment based on the additive effect of multiple polymorphic loci within the APOE promoter region, which on their own may have too weak an impact to reach the level of significance. This has potentially practical implications, as it may help to improve the informative potential of APOE testing in a clinical setting. Subsequent studies of the proposed system in large, multi-ethnic cohorts are necessary for its validation and to assess its potential practical value for clinical applications. PMID- 27193890 TI - Association of diverse bacterial communities in human bile samples with biliary tract disorders: a survey using culture and polymerase chain reaction-denaturing gradient gel electrophoresis methods. AB - Bacterial infection is considered a predisposing factor for disorders of the biliary tract. This study aimed to determine the diversity of bacterial communities in bile samples and their involvement in the occurrence of biliary tract diseases. A total of 102 bile samples were collected during endoscopic retrograde cholangiopancreatography (ERCP). Characterization of bacteria was done using culture and polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) methods. Antimicrobial susceptibility of the isolates was determined based on the Clinical and Laboratory Standards Institute (CLSI) guidelines and identity of the nucleotide sequences of differentiated bands from the DGGE gels was determined based on GenBank data. In total, 41.2 % (42/102) of the patients showed bacterial infection in their bile samples. This infection was detected in 21 % (4/19), 45.4 % (5/11), 53.5 % (15/28), and 54.5 % (24/44) of patients with common bile duct stone, microlithiasis, malignancy, and gallbladder stone, respectively. Escherichia coli showed a significant association with gallstones. Polymicrobial infection was detected in 48 % of the patients. While results of the culture method established coexistence of biofilm-forming bacteria (Pseudomonas aeruginosa, E. coli, Klebsiella pneumoniae, Enterococcus spp., and Acinetobacter spp.) in different combinations, the presence of Capnocytophaga spp., Lactococcus spp., Bacillus spp., Staphylococcus haemolyticus, Enterobacter or Citrobacter spp., Morganella spp., Salmonella spp., and Helicobacter pylori was also characterized in these samples by the PCR-DGGE method. Multidrug resistance phenotypes (87.5 %) and resistance to third- and fourth-generation cephalosporins and quinolones were common in these strains, which could evolve through their selection by bile components. Ability for biofilm formation seems to be a need for polymicrobial infection in this organ. PMID- 27193892 TI - A Concept Analysis of "Follower" Within the Context of Professional Nursing. AB - PROBLEM: Theory and research on leaders is abundant; however, the follower concept is noticeably absent from the leadership literature. METHOD: This article uses Walker and Avant's concept analysis method to explore the concept of follower in professional nursing. A literature search of nursing and psychological databases provided insight into the meaning of a follower. Using the concept exploration approach, defining attributes are proposed along with antecedents and consequences to clarify the concept uses. Model and additional cases provide exemplars of concept application. Finally, the empirical referents of practical use and measurement in the professional environment are presented. CONCLUSION: Although it is clear that leadership without followers is impossible, the fact remains that clarification of which elements constitute followers are on the periphery of current leadership efforts. IMPLICATION FOR NURSING: Conceptual clarity is necessary to improve the way nurse leaders identify situations of following and nonfollowing in professional context and guide how they will engage followers to achieve goals. PMID- 27193891 TI - Staphylococcus aureus colonization related to severity of hand eczema. AB - Knowledge on Staphylococcus aureus colonization rates and epidemiology in hand eczema is limited. The aim of this study was to clarify some of these issues. Samples were collected by the "glove juice" method from the hands of 59 patients with chronic hand eczema and 24 healthy individuals. Swab samples were taken from anterior nares and throat from 43 of the 59 patients and all healthy individuals. S. aureus were spa typed and analysed by DNA-microarray-based genotyping. The extent of the eczema was evaluated by the hand eczema extent score (HEES). The colonization rate was higher on the hands of hand eczema patients (69 %) compared to healthy individuals (21 %, p < 0.001). This was also seen for bacterial density (p = 0.002). Patients with severe hand eczema (HEES >= 13) had a significantly higher S. aureus density on their hands compared to those with milder eczema (HEES = 1 to 12, p = 0.004). There was no difference between patients and healthy individuals regarding colonization rates in anterior nares or throat. spa typing and DNA-microarray-based genotyping indicated certain types more prone to colonize eczematous skin. Simultaneous colonization, in one individual, with S. aureus of different types, was identified in 60-85 % of the study subjects. The colonization rate and density indicate a need for effective treatment of eczema and may have an impact on infection control in healthcare. PMID- 27193893 TI - Neuromonitoring Using Motor and Somatosensory Evoked Potentials in Aortic Surgery. AB - BACKGROUND: Motor evoked potentials (MEP) and somatosensory evoked potentials (SSEP) are established methods of neuromonitoring aimed at preventing paraplegia after descending or thoracoabdominal aortic repair. However, their predictive impact remains controversial. The aim of this study was to evaluate our single center experience using this monitoring technique. METHODS: Between 2009 and 2014, 78 patients (mean age 66 +/- 12, 53% male) underwent either descending or thoracoabdominal aortic repairs. Of these, 60% had an aortic aneurysm, 30% dissection, and 10% other etiologies. Intraoperatively, MEPs and SSEPs were monitored and, if necessary, clinical parameters (blood pressure, hematocrit, oxygenation) were adjusted in response to neuromonitoring signals. This analysis is focused on the neurological outcome (paraplegia, stroke) after the use of intraoperative neuromonitoring. RESULTS: Thirty-day mortality was 10 (12.8%). All patients with continuously stable signals or signals that returned after signal loss developed no spinal cord injury, whereas two out of six of the evaluable patients with signal loss (without return) during the procedure suffered from postoperative paraplegia (one transient and one permanent). Sensitivity and specificity of use of MEP and SSEP were 100% and 94.20% regarding paraplegia, respectively. CONCLUSIONS: (1) Preservation of signals or return of signals is an excellent prognostic indicator for spinal cord function. (2) Intraoperative modifications in direct response to the signal change may have averted permanent paralysis in the patients with signal loss without neurologic injury. We have found MEP and SSEP neuromonitoring to be instrumental in the prevention of paraplegia. doi: 10.1111/jocs.12739 (J Card Surg 2016;31:383-389). PMID- 27193894 TI - A cold-adapted tyrosinase with an abnormally high monophenolase/diphenolase activity ratio originating from the marine archaeon Candidatus Nitrosopumilus koreensis. AB - OBJECTIVES: To obtain an acidic and cold-active tyrosinase, which potentially minimizes unwanted self-oxidation of tyrosinase-catalyzed catechols, including 3,4-dihydroxyphenylalanine at elevated pH and high temperature. RESULTS: A putative psychrophilic tyrosinase (named as tyrosinase-CNK) was identified from the genome information of the marine archaeon Candidatus Nitrosopumilus koreensis. This protein contains key tyrosinase domains, such as copper-binding domains and an O2-binding motif, and phylogenetic analysis revealed that it was distinct from other known bacterial tyrosinases. Functional tyrosinase-CNK was produced by applying a co-expression strategy together with chaperone proteins in Escherichia coli with a yield of approx. 30 mg l(-1) and a purity >95 %. The purified enzyme showed optimal activity at pH 6 and 20 degrees C and still had 50 % activity at 0 degrees C. Surprisingly, the enzyme exhibited an abnormally high monophenolase/diphenolase activity ratio. CONCLUSIONS: The acidic and cold adapted tyrosinase-CNK, as a new type of tyrosinase, could expand potential applications of tyrosinases including the production of catechols through minimizing unwanted self-oxidation and the modification of existing materials at low temperature. PMID- 27193895 TI - Contribution of direct electron transfer mechanisms to overall electron transfer in microbial fuel cells utilising Shewanella oneidensis as biocatalyst. AB - OBJECTIVES: To investigate the contribution of direct electron transfer mechanisms to electricity production in microbial fuel cells by physically retaining Shewanella oneidensis cells close to or away from the anode electrode. RESULTS: A maximum power output of 114 +/- 6 mWm(-2) was obtained when cells were retained close to the anode using a dialysis membrane. This was 3.5 times more than when the cells were separated away from the anode. Without the membrane the maximum power output was 129 +/- 6 mWm(-2). The direct mechanisms of electron transfer contributed significantly to overall electron transfer from S. oneidensis to electrodes, a result that was corroborated by another experiment where S. oneidensis cells were entrapped in alginate gels. CONCLUSION: S. oneidensis transfers electrons primarily by direct electron transfer as opposed to mediated electron transfer. PMID- 27193896 TI - Characterization of an ene-reductase from Meyerozyma guilliermondii for asymmetric bioreduction of alpha,beta-unsaturated compounds. AB - OBJECTIVES: To characterize a novel ene-reductase from Meyerozyma guilliermondii and achieve the ene-reductase-mediated reduction of activated C=C bonds. RESULTS: The gene encoding an ene-reductase was cloned from M. guilliermondii. Sequence homology analysis showed that MgER shared the maximal amino acid sequence identity of 57 % with OYE2.6 from Scheffersomyces stipitis. MgER showed the highest specific activity at 30 degrees C and pH 7 (100 mM sodium phosphate buffer), and excellent stereoselectivities were achieved for the reduction of (R) carvone and ketoisophorone. Under the reaction conditions (30 degrees C and pH 7.0), 150 mM (R)-carvone could be completely converted to (2R,5R)-dihydrocarvone within 22 h employing purified MgER as catalyst, resulting in a yield of 98.9 % and an optical purity of >99 % d.e. CONCLUSION: MgER was characterized as a novel ene-reductase from yeast and showed great potential for the asymmetric reduction of activated C=C bonds of alpha,beta-unsaturated compounds. PMID- 27193898 TI - HPV testing on self collected cervicovaginal lavage specimens as screening method for women who do not attend cervical screening: cohort study. PMID- 27193899 TI - Mechanisms of Neuronal Cell Death in AGE-exposed Retinas - Research and Literature Review. AB - INTRODUCTION: Accelerated formation of AGE due to increasing rise in blood glucose levels leads to developments of metabolic changes, further leading to such complications as diabetic retinopathy which is a major reason of leading to blindness and affecting working population worldwide. BACKGROUND: The results of recent investigations have demonstrated that the death of retinal ganglion cells (RGCs) and their axons is the common pathological changes in AGE-exposed retina and the possible mechanisms that are responsible for the onset and progression of RGC death and axonal degeneration in patients with diseases associated with AGEs accumulation are represented in this review. Identifying the mechanisms of the onset and the progression of RGC neuropathy can help in discovering the pathogenetic orientated treatment. OBJECTIVE: This review describes recently discovered possible mechanisms of diabetic retinopathy obtained by laboratory studies with the suggestion that AGEs play an important role in the pathogenesis of diabetic retinal neuropathy triggering different mechanisms that result in neuronal dysfunction. For searching therapeutic approach the regenerative effect of different neurotrophic factors has been studied such as neurotrophin-4, hepatocyte growth factor, glial cell line-derived neurotrophic factor, and Tauroursodeoxycholic acid. CONCLUSION: The findings for the establishment of neuroprotective and regenerative therapies for AGE-related diseases including diabetic retinopathy are represented in this review. PMID- 27193897 TI - Why Do Parents Want to Know their Child's Carrier Status? A Qualitative Study. AB - When a child is identified with a genetic condition, some parents want to know the carrier status of their other children. There has been little exploration of why parents want this information. To address this question, semi-structured interviews were conducted with parents of 32 children with cystic fibrosis, haemophilia, and Duchenne muscular dystrophy who wanted to know the carrier status of their other children. Data was analyzed using inductive content analysis. Parents expressed a range of reasons for desiring their child's carrier status, which fell into two broad categories: 1) benefit for the parents and 2) perceived benefit to the child. Parents discussed the desire for certainty and peace of mind derived from having knowledge of their child's status. The most commonly expressed reason for wanting to know their child's carrier status was in order to communicate the information to their child to provide them with the ability to make informed reproductive decisions. These reasons suggest parents are seeking their children's carrier information both as a coping strategy and to communicate carrier information as part of their role as a parent. This has important implications for genetic counseling practice, especially as international guidelines generally recommend against carrier testing in children. PMID- 27193900 TI - Spectral determination of concentrations of functionally diverse pigments in increasingly complex arctic tundra canopies. AB - As the Arctic warms, tundra vegetation is becoming taller and more structurally complex, as tall deciduous shrubs become increasingly dominant. Emerging studies reveal that shrubs exhibit photosynthetic resource partitioning, akin to forests, that may need accounting for in the "big leaf" net ecosystem exchange models. We conducted a lab experiment on sun and shade leaves from S. pulchra shrubs to determine the influence of both constitutive (slowly changing bulk carotenoid and chlorophyll pools) and facultative (rapidly changing xanthophyll cycle) pigment pools on a suite of spectral vegetation indices, to devise a rapid means of estimating within canopy resource partitioning. We found that: (1) the PRI of dark-adapted shade leaves (PRIo) was double that of sun leaves, and that PRIo was sensitive to variation among sun and shade leaves in both xanthophyll cycle pool size (V + A + Z) (r (2) = 0.59) and Chla/b (r (2) = 0.64); (2) A corrected PRI (difference between dark and illuminated leaves, DeltaPRI) was more sensitive to variation among sun and shade leaves in changes to the epoxidation state of their xanthophyll cycle pigments (dEPS) (r (2) = 0.78, RMSE = 0.007) compared to the uncorrected PRI of illuminated leaves (PRI) (r (2) = 0.34, RMSE = 0.02); and (3) the SR680 index was correlated with each of (V + A + Z), lutein, bulk carotenoids, (V + A + Z)/(Chla + b), and Chla/b (r (2) range = 0.52-0.69). We suggest that DeltaPRI be employed as a proxy for facultative pigment dynamics, and the SR680 for the estimation of constitutive pigment pools. We contribute the first Arctic-specific information on disentangling PRI-pigment relationships, and offer insight into how spectral indices can assess resource partitioning within shrub tundra canopies. PMID- 27193902 TI - European Journal of Orthodontics: Editor's Report 2015. PMID- 27193901 TI - Screening North American plant extracts in vitro against Trypanosoma brucei for discovery of new antitrypanosomal drug leads. AB - BACKGROUND: Human African Trypanosomiasis (HAT) is a protozoan parasitic disease caused by Trypanosoma brucei. The disease is endemic in regions of sub-Saharan Africa, covering 36 countries and more than 60 million people at the risk. Only few drugs are available for the treatment of HAT. Current drugs suffer from severe toxicities and require intramuscular or intravenous administrations. The situation is further aggravated due to the emergence of drug resistance. There is an urgent need of new drugs that are effective orally against both stages of HAT. Natural products offer an unmatched source for bioactive molecules with new chemotypes. METHODS: The extracts prepared from 522 plants collected from various parts of the North America were screened in vitro against blood stage trypamastigote forms of T. brucei. Active extracts were further screened at concentrations ranging from 10 to 0.4 MUg/mL. Active extracts were also investigated for toxicity in Differentiated THP1 cells at 10 MUg/mL concentration. The results were computed for dose-response analysis and determination of IC50/IC90 values. RESULTS: A significant number (150) of extracts showed >90 % inhibition of growth of trypomastigote blood forms of T. brucei in primary screening at 20 MUg/mL concentration. The active extracts were further investigated for dose-response inhibition of T. brucei growth. The antitrypansomal activity of 125 plant extracts was confirmed with IC50 < 10 MUg/mL. None of these active extracts showed toxicity against differentiated THP1 cells. Eight plants extracts namely, Alnus rubra, Hoita macrostachya, Sabal minor, Syzygium aqueum, Hamamelis virginiana, Coccoloba pubescens, Rhus integrifolia and Nuphar luteum were identified as highly potent antitrypanosomal extracts with IC50 values <1 MUg/mL. CONCLUSIONS: Limited phytochemical and pharmacological reports are available for the lead plant extracts with potent antitrypanosomal activity. Follow up evaluation of these plant extracts is likely to yield new antitrypanosomal drug-leads or alternate medicines for treatment of HAT. PMID- 27193903 TI - Ventricular tachycardia in repaired congenital heart disease. AB - Ventricular arrhythmias are an important cause of late morbidity and sudden cardiac death in the growing population of adults with repaired congenital heart disease. Risk stratification remains challenging because of the heterogeneity of the malformations and the surgical approaches. Therapeutic interventions depend on the type of ventricular arrhythmia, which can be polymorphic ventricular tachycardia (VT) or ventricular fibrillation in patients without ventricular scars, but also potentially fatal monomorphic reentrant VTs, typical for patients with ventricular scars or obstacles. Advances in surgical techniques have improved survival and have important implications for the arrhythmia substrates and prognosis. Over the past few decades, progress has been made to determine the anatomical basis for monomorphic VT in patients with ventricular surgical scars and patch material. These substrates can be currently identified and targeted during sinus rhythm by radiofrequency catheter or surgical ablation without the need for VT induction. The review provides an update on the evolving surgical approaches, the changing VA substrates, and the potential consequences for individualized risk assessment and tailored treatment. PMID- 27193904 TI - Cost-effectiveness of sorafenib versus SBRT for unresectable advanced hepatocellular carcinoma. AB - OBJECTIVE: Stereotactic body radiotherapy (SBRT) has been shown to improve overall survival in patients with advanced hepatocellular carcinoma. This study aimed to assess the cost-effectiveness of SBRT compared to sorafenib which is the only drug for advanced hepatocellular carcinoma. METHODS: A Markov decision analytic model was performed to compare the cost-effectiveness of SBRT and sorafenib for unresectable advanced hepatocellular carcinoma. Patients transitioned between three health states: stable disease, progression disease and death. We calculated the data on cost from the perspective of our National Health Insurance Bureau. Sensitivity analyses were conducted to determine the impact of several variables. RESULTS: The incremental cost effectiveness ratio (ICER) for sorafenib compared to SBRT was NT$3,788,238 per quality-adjusted life year gained (cost/QALY), which was higher than the willingness to pay threshold of Taiwan according to WHO's guideline. One-way sensitivity analysis revealed that the utility of progression disease for the sorafenib treatment, utility of progression free survival for SBRT, utility of progression free survival for sorafenib, utility of PFS to progression disease for SBRT and transition probability of progression disease to dead for SBRT were the most sensitive parameters in all cost scenarios. The Monte-Carlo simulation demonstrated that the probability of cost-effectiveness at a willingness to pay threshold of NT$ 2,213,145 per QALY was 100 % and 0 % chance for SBRT and sorafenib. CONCLUSION: This study indicated that SBRT for advanced hepatocellular carcinoma is cost effective at a willingness to pay threshold as defined by WHO guideline in Taiwan. PMID- 27193905 TI - Stent Polymers: Do They Make a Difference? AB - The necessity of polymers on drug-eluting stent (DES) platforms is dictated by the need of an adequate amount and optimal release kinetic of the antiproliferative drugs for achieving ideal DES performance. However, the chronic vessel wall inflammation related to permanent polymer persistence after the drug has been eluted might trigger late restenosis and stent thrombosis. Biodegradable polymers have the potential to avoid these adverse events. A variety of biodegradable polymer DES platforms have been clinically tested, showing equal outcomes with the standard-bearer permanent polymer DES within the first year of implantation. At longer-term follow-up, promising lower rates of stent thrombosis have been observed with the early generation biodegradable polymer DES platforms compared to first-generation DES. Whether this safety benefit still persists with newer biodegradable polymer DES generations against second-generation permanent polymer DES needs to be explored. PMID- 27193907 TI - On- versus off-hour care for patients with non-ST-segment elevation myocardial infarction in Germany : Exemplary results within the chest pain unit concept. AB - AIM: The aim of this study was to analyze differences in the timing of invasive management of patients with high-risk acute coronary syndrome without persistent ST-segment elevation (hr-NSTE-ACS) or myocardial infarction without persistent ST segment elevation (NSTEMI) between on- and off-hours in a German chest pain unit (CPU). PATIENTS AND METHODS: We retrospectively enrolled 160 NSTEMI patients in the study, who were admitted to two German CPUs in 2013. Patients presenting on weekdays between 8 a.m. and 6 p.m. were compared with patients presenting during off-hours. Data analysis included time intervals from admission to invasive management (goals: for hr-NSTE-ACS, <2 h; for NSTEMI, <24 h) and the resulting guideline adherence. RESULTS: Guideline-adherent timing of an invasive strategy did not differ significantly between the on-hour (6.5 h [3.0-22.0 h], 79.9 %) and off-hour groups (10.5 h [2.0-20.0 h], 75.3 %; p = 0.94), without additional significant differences between admissions during off-hours Monday to Thursday and weekends (10.0 h [2.0-19.0 h], 75.6 % vs. 7.5 h [2.0-20.0 h], 76.2 %; p = 0.96). CONCLUSION: Our exemplary experience in two different German CPUs demonstrates adequate timing of coronary catheterization in over 75 % of cases, irrespective of admission during on- or off-hours. Nationwide validation of our findings by the German CPU registry is mandatory. PMID- 27193908 TI - [Introduction of PCSK9 inhibitors : New perspectives in treatment and practical implementation]. AB - Proprotein convertase subtilisin/kexin type 9 (PCSK9) is of critical importance in the regulation of the low-density lipoprotein (LDL) receptor-mediated metabolism of cholesterol. The discovery of mutations in the gene encoding PCSK9 in families with an autosomal dominant form of familial hypercholesterolemia (FH), which were later shown to be "gain-of-function" mutations, led to the development of antibodies against PCSK9. The efficacy in markedly reducing levels of LDL-cholesterol and preliminary evidence for benefits in the prevention of cardiovascular diseases indicated that special groups of patients can be more effectively treated. This includes forms of hypercholesterolemia refractory to conventional treatment as well as patients with FH and/or statin intolerance. Further information on long-term efficacy, tolerability and cost-effectiveness of PCSK9 inhibition and possibilities of implementation in the healthcare system are awaited from ongoing clinical outcome trials, such as FOURIER, ODYSSEY OUTCOMES, SPIRE 1 and 2 involving more than 70,000 high-risk patients. PMID- 27193906 TI - Relationship between weight-related behavioral profiles and health outcomes by sexual orientation and gender. AB - OBJECTIVE: Examine relationships between weight-related factors and weight status, body dissatisfaction, chronic health conditions, and quality of life across sexual orientation and gender. METHODS: Two- and four-year college students participated in the College Student Health Survey (n = 28,703; 2009 2013). Risk differences were calculated to estimate relationships between behavioral profiles and weight status, body satisfaction, diagnosis of a chronic condition, and quality of life, stratified by gender and sexual orientation. Four behavioral profiles, characterized as "healthier eating habits, more physically active," "healthier eating habits," "moderate eating habits," and "unhealthy weight control," were utilized based on latent class analyses, estimated from nine weight-related behavioral survey items. RESULTS: Sexual orientation differences in weight and quality of life were identified. For example, sexual minority groups reported significantly poorer quality of life than their heterosexual counterparts (females: 22.5%-38.6% (sexual minority) vs. 19.8% (heterosexual); males: 14.3%-26.7% (sexual minority) vs. 11.8% (heterosexual)). Compared with the "healthier eating habits, more physically active" profile, the "unhealthy weight control" profile was associated with obesity, poor body satisfaction, and poor quality of life in multiple gender/sexual orientation subgroups. CONCLUSIONS: Interventions are needed to address obesity, body dissatisfaction, and poor quality of life among sexual minority college students. PMID- 27193910 TI - Menopausal status and type 2 diabetes: a nationwide epidemiological survey in Vietnam. PMID- 27193909 TI - Gender Interacts with Opioid Receptor Polymorphism A118G and Serotonin Receptor Polymorphism -1438 A/G on Speed-Dating Success. AB - We examined an understudied but potentially important source of romantic attraction-genetics-using a speed-dating paradigm. The mu opioid receptor (OPRM1) polymorphism A118G (rs1799971) and the serotonin receptor (HTR2A) polymorphism 1438 A/G (rs6311) were studied because they have been implicated in social affiliation. Guided by the social role theory of mate selection and prior genetic evidence, we examined these polymorphisms' gender-specific associations with speed-dating success (i.e., date offers, mate desirability). A total of 262 single Asian Americans went on speed-dates with members of the opposite gender and completed interaction questionnaires about their partners. Consistent with our prediction, significant gender-by-genotype interactions were found for speed dating success. Specifically, the minor variant of A118G (G-allele), which has been linked to submissiveness/social sensitivity, predicted greater speed-dating success for women, whereas the minor variant of -1438 A/G (G-allele), which has been linked to leadership/social dominance, predicted greater speed-dating success for men. For both polymorphisms, reverse "dampening" effects of minor variants were found for opposite-gender counterparts. These results support previous research on the importance of the opioid and serotonergic systems in social affiliation, indicating that their influence extends to dating success, with opposite, yet gender-norm consistent, effects for men and women. PMID- 27193911 TI - Uniform electric field generation in circular multi-well culture plates using polymeric inserts. AB - Applying uniform electric field (EF) in vitro in the physiological range has been achieved in rectangular shaped microchannels. However, in a circular-shaped device, it is difficult to create uniform EF from two electric potentials due to different electrical resistances originated from the length difference between the diameter of the circle and the length of any parallel chord of the bottom circular chamber where cells are cultured. To address this challenge, we develop a three-dimensional (3D) computer-aided designed (CAD) polymeric insert to create uniform EF in circular shaped multi-well culture plates. A uniform EF with a coefficient of variation (CV) of 1.2% in the 6-well plate can be generated with an effective stimulation area percentage of 69.5%. In particular, NIH/3T3 mouse embryonic fibroblast cells are used to validate the performance of the 3D designed Poly(methyl methacrylate) (PMMA) inserts in a circular-shaped 6-well plate. The CAD based inserts can be easily scaled up (i.e., 100 mm dishes) to further increase effective stimulation area percentages, and also be implemented in commercially available cultureware for a wide variety of EF-related research such as EF-cell interaction and tissue regeneration studies. PMID- 27193912 TI - The intriguing relationship between epilepsy and type 1 diabetes mellitus. PMID- 27193913 TI - Erratum to: A proposal for the use of uniform diagnostic criteria for gestational diabetes in Europe: an opinion paper by the European Board & College of Obstetrics and Gynaecology (EBCOG). PMID- 27193914 TI - The intriguing relationship between epilepsy and type 1 diabetes mellitus. Reply to Sander JW, Novy J, Keezer MR [letter]. PMID- 27193915 TI - Parenthood and the risk of diabetes in men and women: a 7 year prospective study of 0.5 million individuals. AB - AIMS/HYPOTHESIS: In women, higher parity has been associated with increased risk of diabetes later in life. It is unclear, however, whether this association is mainly due to biological effects of childbearing, or to socioeconomic and lifestyle factors associated with childrearing. We assessed the association between number of children and diabetes risk separately in women and men. METHODS: Between 2004 and 2008, the nationwide China Kadoorie Biobank recruited 0.5 million individuals aged 30-79 (mean 51 years) from ten diverse regions across China. During 7 years of follow-up, 8,840 incident cases of diabetes were recorded among 463,347 participants without prior cardiovascular diseases or diabetes. Multivariable Cox regression yielded sex-specific HRs and 95% CIs for incident diabetes by number of children. RESULTS: Overall, ~98% of all participants had children. In women, there was a J-shaped association between number of children and risk of diabetes. Compared with women with one child, the adjusted HRs for diabetes were 1.39 (95% CI 1.11, 1.73) for childless women, 1.12 (95% CI 1.07, 1.18) for those with two children, 1.23 (95% CI 1.16, 1.31) for those with three children, and 1.32 (95% CI 1.21, 1.44) for those with four or more children. In men, there was a similar association with risk of diabetes; the corresponding HRs were 1.28 (95% CI 1.02, 1.60), 1.19 (95% CI 1.12, 1.26), 1.32 (95% CI 1.21, 1.44) and 1.41 (95% CI 1.24, 1.60), respectively. In both sexes, the findings were broadly similar in different population subgroups. CONCLUSIONS/INTERPRETATION: The similarity between women and men in the association between number of children and risk of diabetes suggests that parenthood is most likely to affect diabetes risk through factors associated with childrearing rather than via biological effects of childbearing. PMID- 27193916 TI - In vivo PET imaging with [(18)F]FDG to explain improved glucose uptake in an apolipoprotein A-I treated mouse model of diabetes. AB - AIMS/HYPOTHESIS: Type 2 diabetes is characterised by decreased HDL levels, as well as the level of apolipoprotein A-I (apoA-I), the main apolipoprotein of HDLs. Pharmacological elevation of HDL and apoA-I levels is associated with improved glycaemic control in patients with type 2 diabetes. This is partly due to improved glucose uptake in skeletal muscle. METHODS: This study used kinetic modelling to investigate the impact of increasing plasma apoA-I levels on the metabolism of glucose in the db/db mouse model. RESULTS: Treatment of db/db mice with apoA-I for 2 h significantly improved both glucose tolerance (AUC 2574 +/- 70 mmol/l * min vs 2927 +/- 137 mmol/l * min, for apoA-I and PBS, respectively; p < 0.05) and insulin sensitivity (AUC 388.8 +/- 23.8 mmol/l * min vs 194.1 +/- 19.6 mmol/l * min, for apoA-I and PBS, respectively; p < 0.001). ApoA-I treatment also increased glucose uptake by skeletal muscle in both an insulin-dependent and insulin-independent manner as evidenced by increased uptake of fludeoxyglucose ([(18)F]FDG) from plasma into gastrocnemius muscle in apoA-I treated mice, both in the absence and presence of insulin. Kinetic modelling revealed an enhanced rate of insulin-mediated glucose phosphorylation (k 3) in apoA-I treated mice (3.5 +/- 1.1 * 10(-2) min(-1) vs 2.3 +/- 0.7 * 10(-2) min(-1), for apoA-I and PBS, respectively; p < 0.05) and an increased influx constant (3.7 +/- 0.6 * 10( 3) ml min(-1) g(-1) vs 2.0 +/- 0.3 * 10(-3) ml min(-1) g(-1), for apoA-I and PBS, respectively; p < 0.05). Treatment of L6 rat skeletal muscle cells with apoA-I for 2 h indicated that increased hexokinase activity mediated the increased rate of glucose phosphorylation. CONCLUSIONS/INTERPRETATION: These findings indicate that apoA-I improves glucose disposal in db/db mice by improving insulin sensitivity and enhancing glucose phosphorylation. PMID- 27193918 TI - Quantifying the impact of different approaches for handling continuous predictors on the performance of a prognostic model. AB - Continuous predictors are routinely encountered when developing a prognostic model. Investigators, who are often non-statisticians, must decide how to handle continuous predictors in their models. Categorising continuous measurements into two or more categories has been widely discredited, yet is still frequently done because of its simplicity, investigator ignorance of the potential impact and of suitable alternatives, or to facilitate model uptake. We examine three broad approaches for handling continuous predictors on the performance of a prognostic model, including various methods of categorising predictors, modelling a linear relationship between the predictor and outcome and modelling a nonlinear relationship using fractional polynomials or restricted cubic splines. We compare the performance (measured by the c-index, calibration and net benefit) of prognostic models built using each approach, evaluating them using separate data from that used to build them. We show that categorising continuous predictors produces models with poor predictive performance and poor clinical usefulness. Categorising continuous predictors is unnecessary, biologically implausible and inefficient and should not be used in prognostic model development. (c) 2016 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd. PMID- 27193920 TI - Do Physicians Change Prescription Practice in Response to Financial Incentives? AB - We assessed the impact on physician prescription behaviors of an outpatient prescription incentive program providing financial rewards to primary care physicians for saving prescription costs in South Korea. A 10% sample of clinics (N = 1,625) was randomly selected from all clinics in the National Health Insurance claims database for the years 2009-2012, and all claims with the primary diagnosis of peptic ulcer or gastro-esophageal reflux diseases were extracted from those clinics' data. A clinic-level random-effects model was used. After the program, clinics in general medicine showed a lower prescription rate (by 0.8 percentage points), lower number of medicines prescribed (by 0.02), lower prescription duration (by 0.15 days), and lower drug expenditure per claim (by 740 won). Small clinics on the <25th percentile of a regional sum of monthly drug expenditure had shorter prescription duration (by 0.76 days), while large clinics on the >=75th percentile and clinics in group practice had a higher prescription rate (by 1.5 and 2.5 percentage points, respectively) and a higher number of medicines prescribed (by 0.03 for group practice only) after the program. The outpatient prescription incentive program worked as intended only in certain subgroup clinics for the target medicines. PMID- 27193917 TI - Improving the Recognition of, and Response to In-Hospital Sepsis. AB - Sepsis is an important cause of patient morbidity and mortality worldwide. Although the associated mortality seems to be decreasing, approximately 20 % of patients with organ dysfunction die in hospital. Since 1991 diagnostic criteria for sepsis focused on the systemic inflammatory response syndrome (SIRS). However, the utility of such criteria has been questioned, and alternative criteria have recently been proposed. It is likely that administration of early appropriate antibiotics and resolution of shock reduce sepsis-associated mortality. Accordingly, strategies need to be developed to improve the early recognition of, and response to patients with sepsis. Such system approaches may include improved acquisition and documentation of vital signs, enhanced recognition of shock, and integration of laboratory and microbiological results using clinical informatics. Hospitals should have guidelines for escalating care of septic patients, antibiotics stewardship programs, and systems to audit morbidity and mortality associated with sepsis. PMID- 27193921 TI - Quantitative real-time detection of carcinoembryonic antigen (CEA) from pancreatic cyst fluid using 3-D surface molecular imprinting. AB - In this study, a sensitive, yet robust, biosensing system with real-time electrochemical readout was developed. The biosensor system was applied to the detection of carcinoembryonic antigen (CEA), which is a common marker for many cancers such as pancreatic, breast, and colon cancer. Real time detection of CEA during a medical procedure can be used to make critical decisions regarding further surgical intervention. CEA was templated on gold surface (RMS roughness ~3-4 nm) coated with a hydrophilic self-assembled monolayer (SAM) on the working electrode of an open circuit potentiometric network. The subsequent removal of template CEA makes the biosensor capable of CEA detection based on its specific structure and conformation. The molecular imprinting (MI) biosensor was further calibrated using the potentiometric responses in solutions with known CEA concentrations and a detection limit of 0.5 ng ml(-1) was achieved. Potentiometric sensing was then applied to pancreatic cyst fluid samples obtained from 18 patients when the cyst fluid was also evaluated using ELISA in a certified pathology laboratory. Excellent agreement was obtained between the quantitation of CEA obtained by both the ELISA and MI biosensor detection for CEA. A 3-D MI model, using the natural rms roughness of PVD gold layers, is presented to explain the high degree of sensitivity and linearity observed in those experiments. PMID- 27193922 TI - [GROUP 2 INNATE LYMPHOID CELLS AND ALLERGIC DISEASES]. PMID- 27193923 TI - [ALLERGENS]. PMID- 27193919 TI - Fast response to human voices in autism. AB - Individuals with autism spectrum disorders (ASD) are reported to allocate less spontaneous attention to voices. Here, we investigated how vocal sounds are processed in ASD adults, when those sounds are attended. Participants were asked to react as fast as possible to target stimuli (either voices or strings) while ignoring distracting stimuli. Response times (RTs) were measured. Results showed that, similar to neurotypical (NT) adults, ASD adults were faster to recognize voices compared to strings. Surprisingly, ASD adults had even shorter RTs for voices than the NT adults, suggesting a faster voice recognition process. To investigate the acoustic underpinnings of this effect, we created auditory chimeras that retained only the temporal or the spectral features of voices. For the NT group, no RT advantage was found for the chimeras compared to strings: both sets of features had to be present to observe an RT advantage. However, for the ASD group, shorter RTs were observed for both chimeras. These observations indicate that the previously observed attentional deficit to voices in ASD individuals could be due to a failure to combine acoustic features, even though such features may be well represented at a sensory level. PMID- 27193925 TI - [A FEATURE OF JPGL2012 WHEN COMPARED WITH GINA2014]. PMID- 27193924 TI - [MODIFIER FACTORS OF ALLERGIC RHINITIS AND EOSINOPHILIC RHINOSINUSITS: CLINICAL APPLICATION]. PMID- 27193926 TI - [SWEAT ALLERGY IN ATOPIC DERMATITIS]. PMID- 27193927 TI - [A NOVEL TYPE OF INNATE LYMPHOID CELLS 'FAS-EXPRESSING NATURAL HELPER CELLS']. PMID- 27193928 TI - [METHODS OF INGESTION IN ORAL FOOD CHALLENGE TESTS USING WHOLE-EGG POWDER]. AB - BACKGROUND AND OBJECTIVE: Preparation of the food for an oral food challenge (OFC) test is complicated. We prospectively examined the results of an inpatient oral food challenge test involving the use of juice containing whole-egg powder (egg juice) prepared by NH Foods Ltd. and conducted in the Department of Pediatrics of Sagamihara National Hospital. METHODS AND SUBJECTS: We prospectively evaluated the results of an egg-juice (equivalent to half of an egg) OFC test conducted in Sagamihara National Hospital between September 2014 and April 2015 in 116 cases for diagnosis or tolerance acquisition. RESULTS: The OFC test positivity rate was 33%. Severity according to the anaphylaxis guidelines was grade 1 (mild; 42%), grade 2 (moderate; 53%), and grade 3 (severe; 5%) in the patients with positive test results. Among the 78 subjects with negative results for intakes at home, 92% had no symptoms, with the remaining 8% having mild symptoms but requiring no treatment. We could confirm later that all the patients could eat foods containing half of a chicken egg. CONCLUSION: For the subjects with negative egg-juice OFC test results, eating egg products equivalent to half of an egg at home seemed to be relatively safe. PMID- 27193929 TI - [A CASE OF ANAPHYLAXIS IN THE PEDIATRIC PATIENT WITH MILK ALLERGY DUE TO TRACES OF MILK PROTEIN IN THE LACTOSE USED AS AN EXCIPIENT OF INAVIR INHALATION]. AB - The patient was a 6-year-old female with milk allergy and persistent asthma. She experienced anaphylactic reactions just after the inhalation of Inavir (Laninamivir Octanoate Hydrate) to treat flu infection. A skin-prick test showed positive reactions for Inavir inhaler powder and lactose used as an excipient but negative for Laninamivir. Same results were obtained in a drug-stimulated basophil activation test. The lactose excipient in Inavir inhaler powder was supposed to contain milk proteins, which caused anaphylactic reactions. To test this possibility, we examined the contamination of allergic milk proteins in the lactose excipient and found the smear band by silver staining, which was identified as beta-lactoglobulin (beta-LG) by Western blotting using specific monoclonal antibody and patient's sera. The beta-LG in Inavir was supposed to be glycosylated with lactose because the molecular weight was slightly higher than beta-LG standard reference as seen in mobility. In fact, the incubation with lactose in vitro tended to increase molecular weight. Following these results, we herein report that the trace amounts of beta-LG contaminated in the lactose excipient of Inavir could cause immediate allergic reactions. The risk that the lactose-containing dry powder inhalers cause allergic reactions for patients with cow's milk allergy need to be reminded. In particular, the use for flu patients should be paid careful attention because of increased airway hypersensitivity in those patients. PMID- 27193930 TI - [Not Available]. PMID- 27193931 TI - [Not Available]. PMID- 27193932 TI - [Asthma-COPD Overlap Syndrome]. PMID- 27193933 TI - Co-morbidity of depression, anxiety and fatigue in cancer patients receiving psychological care. AB - OBJECTIVES: This study aimed to examine (1) subgroups of cancer patients with distinct co-morbidity patterns of depression, anxiety and fatigue; (2) how individuals transitioned between these patterns; and (3) whether socio demographic, clinical and psychological care characteristics distinguished patients' transitions. METHOD: This naturalistic, longitudinal study focused on 241 cancer patients receiving psycho-oncological care in the Netherlands. Data were collected before initiation of psychological care (T1), 3 months (T2), and 9 months thereafter (T3). Latent transition analysis was performed examining research questions. RESULTS: Three distinct co-morbidity patterns were identified: class 1 ('mood disturbances and fatigue'), class 2 ('mood disturbances') and class 3 ('few symptoms of mood disturbances and fatigue'). Half of those in class 1 remained in this group from T1 to T3, a quarter transitioned to class 2 and another quarter to class 3. Baseline physical symptoms distinguished these transitions: those with more physical symptoms tended to remain stable. Half of patients in class 2 remained stable from T1 to T3, 46% moved into class 3 and 8% into class 1. Baseline physical symptoms and years after cancer diagnosis significantly distinguished these transitions: the 8% moving to class 1 had more physical symptoms and were longer after cancer diagnosis. Most patients in class 3 remained stable from T1 to T3, and predictors of transitions could not be examined. CONCLUSIONS: Three distinct co-morbidity patterns of depression, anxiety and fatigue were identified and exhibited different symptom courses longitudinally. Those with poor physical health tended to report elevated mood disturbances and fatigue during psychological care. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27193935 TI - Synthesis and piezochromic luminescence study of a coumarin hydrozone compound. AB - A novel coumarin hydrozone compound which exhibits piezochromic luminescence upon grinding was prepared. The piezofluorochromic properties were reversible upon fuming or heating. The intermolecular hydrogen bonds have been observed by single crystal X-ray structural analysis, which are believed to make a major contribution to the piezofluorochromic properties. PMID- 27193934 TI - Presurgical motor, somatosensory and language fMRI: Technical feasibility and limitations in 491 patients over 13 years. AB - OBJECTIVES: To analyse the long-term feasibility and limitations of presurgical fMRI in a cohort of tumour and epilepsy patients with different MR-scanners at 1.5 and 3.0 T. METHODS: Four hundred and ninety-one consecutive patients undergoing presurgical fMRI between 2000 and 2012 on five different MR-scanners using established paradigms and semi-automated data processing were included. Success rates of task performance and BOLD-activation were determined for motor and somatosensory somatotopic mapping and language localisation. Procedural success, failures and imaging artifacts were analysed. MR-field strengths were compared. RESULTS: Two thousand three hundred fifteen of 2348 (98.6 %) attempted paradigms (1033 motor, 1220 speech, 95 somatosensory) were successfully performed. 100 paradigms (4.3 %) were repetition runs. 23 speech, 6 motor and 2 sensory paradigms failed for non-compliance and technical issues. Most language paradigm failures were noted in overt sentence generation. Average significant BOLD-activation was higher for motor than language paradigms (95.8 vs. 81.6 %). Most language paradigms showed significantly higher activation rates at 3 T compared to 1.5 T, whereas no significant difference was found for motor paradigms. CONCLUSIONS: fMRI proved very robust for the presurgical localisation of the different motor and somatosensory body representations, as well as Broca's and Wernicke's language areas across different MR-scanners at 1.5 and 3.0 T over 13 years. KEY POINTS: * Standardised presurgical motor and language fMRI is robust across various MRI platforms. * Motor fMRI is less dependent on field strength than language fMRI. * fMRI task failures are relatively low and are reduced by paradigm repetition. PMID- 27193937 TI - Preface. PMID- 27193936 TI - Geometric spin echo under zero field. AB - Spin echo is a fundamental tool for quantum registers and biomedical imaging. It is believed that a strong magnetic field is needed for the spin echo to provide long memory and high resolution, since a degenerate spin cannot be controlled or addressed under a zero magnetic field. While a degenerate spin is never subject to dynamic control, it is still subject to geometric control. Here we show the spin echo of a degenerate spin subsystem, which is geometrically controlled via a mediating state split by the crystal field, in a nitrogen vacancy centre in diamond. The demonstration reveals that the degenerate spin is protected by inherent symmetry breaking called zero-field splitting. The geometric spin echo under zero field provides an ideal way to maintain the coherence without any dynamics, thus opening the way to pseudo-static quantum random access memory and non-invasive biosensors. PMID- 27193938 TI - Bone-associated gene evolution and the origin of flight in birds. AB - BACKGROUND: Bones have been subjected to considerable selective pressure throughout vertebrate evolution, such as occurred during the adaptations associated with the development of powered flight. Powered flight evolved independently in two extant clades of vertebrates, birds and bats. While this trait provided advantages such as in aerial foraging habits, escape from predators or long-distance travels, it also imposed great challenges, namely in the bone structure. RESULTS: We performed comparative genomic analyses of 89 bone associated genes from 47 avian genomes (including 45 new), 39 mammalian, and 20 reptilian genomes, and demonstrate that birds, after correcting for multiple testing, have an almost two-fold increase in the number of bone-associated genes with evidence of positive selection (~52.8 %) compared with mammals (~30.3 %). Most of the positive-selected genes in birds are linked with bone regulation and remodeling and thirteen have been linked with functional pathways relevant to powered flight, including bone metabolism, bone fusion, muscle development and hyperglycemia levels. Genes encoding proteins involved in bone resorption, such as TPP1, had a high number of sites under Darwinian selection in birds. CONCLUSIONS: Patterns of positive selection observed in bird ossification genes suggest that there was a period of intense selective pressure to improve flight efficiency that was closely linked with constraints on body size. PMID- 27193939 TI - Influence of ultrasonic tip distance and orientation on biofilm removal. AB - OBJECTIVE: The aim of this study is to assess the effects of ultrasonic tip distance and orientation on the removal of a multispecies biofilm under standardized conditions in vitro. METHODS: Six-species biofilms were grown on hydroxyapatite discs for 64 h and treated with a magnetostrictive ultrasonic tip (Cavitron) placed either on contact or at 0.25- and 0.5-mm distance. The treatment was performed for 15 s with either the tip at right angle or sideways. Biofilm removal was evaluated by assessing the viable bacteria in each supernatant and compared to respective controls. In the latter, biofilms were mechanically removed and evaluated in supernatants to assess adhering and floating bacteria. Colony-forming units (CFU) were determined by cultivation on solid media. Any remaining biofilm on the treated discs was also visualized after staining with green-fluorescent SYTO(r) 9 stain using a confocal laser scanning microscope (CLSM). Mann-Whitney U tests and Bonferroni correction were used to analyze the results between the groups. RESULTS: Sideways application of the ultrasonic tip at distances of 0.25 and 0.5 mm removed as many bacteria as present on the control discs compared to the tip on contact (p < 0.05). All other application modes, especially the ultrasonic tip applied perpendicularly on contact, showed no statistical significance in removing biofilm. CONCLUSION: Overall, data indicated that bacterial detachment depended on tip orientation and distance, especially when the tip was applied sideways similar to the clinical setting. CLINICAL RELEVANCE: Biofilm removal by means of ultrasonic debridement remains a crucial aspect in the treatment of periodontal disease. To ensure sufficient biofilm removal, the tip does not necessarily require contact to the surface, but an application parallel to the surface on the side is recommended. PMID- 27193943 TI - Feasibility of Exercise Training in Cancer Patients Scheduled for Elective Gastrointestinal Surgery. AB - BACKGROUND/AIMS: This study examines the feasibility of a preoperative exercise program to improve the physical fitness of a patient before gastrointestinal surgery. METHODS: An outpatient exercise program was developed to increase preoperative aerobic capacity, peripheral muscle endurance and respiratory muscle function in patients with pancreatic, liver, intestinal, gastric or esophageal cancer. During a consult at the outpatient clinic, patients were invited to participate in the exercise program when their surgery was not scheduled within 2 weeks. RESULTS: The 115 participants followed on average 5.7 (3.5) training sessions. Adherence to the exercise program was high: 82% of the planned training sessions were attended, and no adverse events occurred. Mixed model analyses showed a significant increase of maximal inspiratory muscle strength (84.1-104.7 cm H2O; p = 0.00) and inspiratory muscle endurance (35.0-39.5 cm H2O; p = 0.00). No significant changes were found in aerobic capacity and peripheral muscle strength. CONCLUSION: This exercise program in patients awaiting oncological surgery is feasible in terms of participation and adherence. Inspiratory muscle function improved significantly as a result of inspiratory muscle training. The exercise program however failed to result in improved aerobic capacity and peripheral muscle strength, probably due to the limited number of training sessions as a result of the restricted time interval between screening and surgery. PMID- 27193941 TI - Percutaneous Radiofrequency Ablation of Unresectable Locally Advanced Pancreatic Cancer: Preliminary Results. AB - AIM: The objective of this study was to evaluate the efficacy of percutaneous radiofrequency ablation of locally advanced pancreatic cancer located in the pancreatic body. MATERIALS AND METHODS: Patients with biopsy-proven locally advanced pancreatic adenocarcinoma were considered for percutaneous radiofrequency ablation. Postprocedural computed tomography studies and Ca19.9 tumor marker evaluation were performed at 24 hours and 1 month. At computed tomography, treatment effect was evaluated by excluding the presence of complications. The technical success of the procedure is defined at computed tomography as the achievement of tumoral ablated area. RESULTS: Twenty-three patients have been included in the study. Five of the 23 patients were excluded. At computed tomography, the mean size of the intralesional postablation necrotic area was 32 mm (range: 15-65 mm). Technical success of the procedure has been obtained in 16 (93%) of the 18 cases. None of the patients developed postprocedural complications. Mean Ca19.9 serum levels 1 day before, 1 day after, and 1 month after the procedure were 285.8 U/mL (range: 16.6-942.0 U/mL), 635.2 U/mL (range: 17.9-3368.0 U/mL), and 336.0 U/mL (range: 7.0-1400.0 U/mL), respectively. Follow-up duration was less than 6 months for 11 patients and more than 6 months for 7 patients. At the time of the draft of this article, the mean survival of the patients included in the study was 185 days (range: 62-398 days). CONCLUSION: Percutaneous radiofrequency ablation of locally advanced adenocarcinoma has a high technical success rate and is effective in cytoreduction both at imaging and laboratory controls. PMID- 27193942 TI - Dynamic compression of dense oxide (Gd3Ga5O12) from 0.4 to 2.6 TPa: Universal Hugoniot of fluid metals. AB - Materials at high pressures and temperatures are of great current interest for warm dense matter physics, planetary sciences, and inertial fusion energy research. Shock-compression equation-of-state data and optical reflectivities of the fluid dense oxide, Gd3Ga5O12 (GGG), were measured at extremely high pressures up to 2.6 TPa (26 Mbar) generated by high-power laser irradiation and magnetically-driven hypervelocity impacts. Above 0.75 TPa, the GGG Hugoniot data approach/reach a universal linear line of fluid metals, and the optical reflectivity most likely reaches a constant value indicating that GGG undergoes a crossover from fluid semiconductor to poor metal with minimum metallic conductivity (MMC). These results suggest that most fluid compounds, e.g., strong planetary oxides, reach a common state on the universal Hugoniot of fluid metals (UHFM) with MMC at sufficiently extreme pressures and temperatures. The systematic behaviors of warm dense fluid would be useful benchmarks for developing theoretical equation-of-state and transport models in the warm dense matter regime in determining computational predictions. PMID- 27193944 TI - N-acetylcysteine regimens for paracetamol overdose: Time for a change? AB - Paracetamol overdose is one of the commonest pharmaceutical poisonings in the world. For nearly four decades, intravenous acetylcysteine regimens have been used to treat most patients successfully and prevent or mitigate hepatotoxicity. However, the rate of occurrence of adverse reactions to acetylcysteine is quite high, and there is a potential for these to be reduced. Recent studies show that distributing the loading-dose of acetylcysteine over the first few hours of treatment may decrease the incidence of adverse reactions. In addition, varying the duration of acetylcysteine administration may potentially benefit certain cohorts of poisoned patients, depending on their risk of developing hepatotoxicity. PMID- 27193946 TI - Power considerations for lambda inflation factor in meta-analyses of genome-wide association studies. AB - The genomic control (GC) approach is extensively used to effectively control false positive signals due to population stratification in genome-wide association studies (GWAS). However, GC affects the statistical power of GWAS. The loss of power depends on the magnitude of the inflation factor (lambda) that is used for GC. We simulated meta-analyses of different GWAS. Minor allele frequency (MAF) ranged from 0.001 to 0.5 and lambda was sampled from two scenarios: (i) random scenario (empirically-derived distribution of real lambda values) and (ii) selected scenario from simulation parameter modification. Adjustment for lambda was considered under single correction (within study corrected standard errors) and double correction (additional lambda corrected summary estimate). MAF was a pivotal determinant of observed power. In random lambda scenario, double correction induced a symmetric power reduction in comparison to single correction. For MAF 1.2 and MAF >5%. Our results provide a quick but detailed index for power considerations of future meta-analyses of GWAS that enables a more flexible design from early steps based on the number of studies accumulated in different groups and the lambda values observed in the single studies. PMID- 27193945 TI - Azacitidine: A Review in Myelodysplastic Syndromes and Acute Myeloid Leukaemia. AB - Azacitidine (Vidaza((r))) is a pyrimidine nucleoside analogue of cytidine and is approved in the EU for use in patients with higher-risk myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML), including older patients (aged >=65 years) with AML with >30 % bone marrow blasts (BMB) who are ineligible for haematopoietic stem cell transplant. This article reviews the clinical efficacy and tolerability of azacitidine in the treatment of these patient populations, as well as summarizing its pharmacological properties. In pivotal, international, phase 3 trials, subcutaneous azacitidine was an effective and well tolerated treatment in patients with higher-risk MDS or AML, including older patients with AML with >30 % BMB, with extensive evidence from the real-world setting confirming its efficacy and safety in these patient populations. Azacitidine is the only approved hypomethylating agent that has been shown to prolong overall survival compared with conventional care regimens and thus, it is recommended as the first-line hypomethylating agent for most patients with higher-risk MDS. Hence, azacitidine remains and important agent for use in the treatment of higher risk MDS and AML, including in older patients with AML with >30 % BMB. PMID- 27193947 TI - Phosphodiesterase MoPdeH targets MoMck1 of the conserved mitogen-activated protein (MAP) kinase signalling pathway to regulate cell wall integrity in rice blast fungus Magnaporthe oryzae. AB - In the rice blast fungus Magnaporthe oryzae, the high-affinity cyclic adenosine monophosphate (cAMP) phosphodiesterase MoPdeH is important not only for cAMP signalling and pathogenicity, but also for cell wall integrity (CWI) maintenance through an unknown mechanism. By utilizing affinity purification, we found that MoPdeH interacts with MoMck1, one of the components of the mitogen-activated protein (MAP) kinase cascade that regulates CWI. Overexpression of MoMCK1 suppressed defects in autolysis and pathogenicity of the DeltaMopdeH mutant, although partially, suggesting that MoPdeH plays a critical role in CWI maintenance mediated by the MAP kinase pathway. We found that MoMck1 and two other MAP kinase cascade components, MoMkk1 and MoMps1, modulate intracellular cAMP levels by regulating the expression of MoPDEH through a feedback loop. In addition, disruption of MoMKK1 resulted in less aerial hyphal formation, defective asexual development and attenuated pathogenicity. Moreover, MoMkk1 plays a role in the response to osmotic stress via regulation of MoOsm1 phosphorylation levels, whereas endoplasmic reticulum (ER) stress enhances MoMps1 phosphorylation and loss of the MAP kinase cascade component affects the unfolded protein response (UPR) pathway. Taken together, our findings demonstrate that MoPdeH functions upstream of the MoMck1-MoMkk1-MoMps1 MAP kinase pathway to regulate CWI, and that MoPdeH also mediates crosstalk between the cAMP signalling pathway, the osmotic sensing high osmolarity glycerol (HOG) pathway and the dithiothreitol (DTT)-induced UPR pathway in M. oryzae. PMID- 27193948 TI - Some Possible Cases of Escape Mimicry in Neotropical Butterflies. AB - The possibility that escape or evasive mimicry evolved in butterflies and other prey insects in a similar fashion to classical Batesian and Mullerian mimicry has long been advanced in the literature. However, there is a general disagreement among lepidopterists and evolutionary biologists on whether or not escape mimicry exists, as well as in which mimicry rings this form of mimicry has evolved. Here, we review some purported cases of escape mimicry in Neotropical butterflies and suggest new mimicry rings involving several species of Archaeoprepona, Prepona, and Doxocopa (the "bright blue bands" ring) and species of Colobura and Hypna (the "creamy bands" ring) where the palatability of butterflies, their ability to escape predator attacks, geographic distribution, relative abundance, and co occurrence in the same habitats strongly suggest that escape mimicry is involved. In addition, we also indicate other butterfly taxa whose similarities of coloration patterns could be due to escape mimicry and would constitute important case studies for future investigation. PMID- 27193949 TI - A Comparison of Social Bee-Plant Networks between Two Urban Areas. AB - In the last decade, several studies demonstrated the effectiveness of ecological network analysis to a better understanding of the structure bee-plant interaction networks; however, such approaches involving urban areas are still scarce. Here, we analyzed two assemblages of corbiculate bees (Apoidea, Apidae) in two geographically distinct urban areas in Brazil. In both study areas, apid bees visiting flowers were captured with an insect net. Surveys were performed biweekly and alternately in each area, over a 1-year period. Both urban areas were very similar for most indices. The two social bee-plant networks were significantly nested, a pattern usually described for bee-plant networks and somehow expected in our study, considering the recognized behavior of social apid bees in exploring a wide range of plant species. The modularity measures were low and very similar for the networks of both urban areas, a finding that could be due at least in part to the low phylogenetic distance between corbiculate bees and the broad dietary habits of the social apid bees. Network-level indices showed that both bee assemblages had a relatively low niche overlap, indicating that the set of social apid species studied exploited differently the arrays of plants available. Species level index (resource range) showed that in both urban areas, Trigona spinipes (Fabr.) and Apis mellifera L. showed the higher number of interactions, a result that demonstrates the importance of these species in social bee-plant interaction networks in urban areas. Similarly to other ecosystems, these two apid species behaved as super-generalists in the two urban areas surveyed herein. PMID- 27193950 TI - Field Evaluation of Different Wavelengths Light-Emitting Diodes as Attractants for Adult Aleurodicus dispersus Russell (Hemiptera: Aleyrodidae). AB - In recent years, light traps with light-emitting diodes (LEDs) have been widely used in integrated pest management. The spiralling whitefly, Aleurodicus dispersus Russell, a highly invasive pest which causes heavy damage to fruit trees and ornamental plants, exhibits positive phototaxis, and light trap is the most appropriate tool for monitoring. We evaluated the use of LEDs as an inexpensive light source and examined the relationship between the captured number and the population density of adult A. dispersus in the field. We found that the violet (405 nm) LED traps captured the most adults of A. dispersus, and the captured numbers were significantly higher than those of blue (460 nm), green (520 nm), yellow (570 nm), and red (650 nm) LED traps. The adults of A. dispersus captured by light traps equipped with violet LEDs and smeared with liquid paraffin had a significant positive correlation with the population density of adult A. dispersus in a guava orchard, with a correlation coefficient of 0.828. In general, the light traps with 15 violet LED bulbs hung into 550-mL plastic bottles and smeared with liquid paraffin were the portable devices for attraction of adult A. dispersus. The results have potential use for improving the efficiency of light traps at attracting and trapping the adult spiralling whitefly. PMID- 27193951 TI - Spatial Distribution and Minimum Sample Size for Overwintering Larvae of the Rice Stem Borer Chilo suppressalis (Walker) in Paddy Fields. AB - The rice stem borer, Chilo suppressalis (Walker), feeds almost exclusively in paddy fields in most regions of the world. The study of its spatial distribution is fundamental for designing correct control strategies, improving sampling procedures, and adopting precise agricultural techniques. Field experiments were conducted during 2011 and 2012 to estimate the spatial distribution pattern of the overwintering larvae. Data were analyzed using five distribution indices and two regression models (Taylor and Iwao). All of the indices and Taylor's model indicated random spatial distribution pattern of the rice stem borer overwintering larvae. Iwao's patchiness regression was inappropriate for our data as shown by the non-homogeneity of variance, whereas Taylor's power law fitted the data well. The coefficients of Taylor's power law for a combined 2 years of data were a = -0.1118, b = 0.9202 +/- 0.02, and r (2) = 96.81. Taylor's power law parameters were used to compute minimum sample size needed to estimate populations at three fixed precision levels, 5, 10, and 25% at 0.05 probabilities. Results based on this equation parameters suggesting that minimum sample sizes needed for a precision level of 0.25 were 74 and 20 rice stubble for rice stem borer larvae when the average larvae is near 0.10 and 0.20 larvae per rice stubble, respectively. PMID- 27193952 TI - Longitudinal Distribution of the Functional Feeding Groups of Aquatic Insects in Streams of the Brazilian Cerrado Savanna. AB - We demonstrate that the distribution of the functional feeding groups of aquatic insects is related to hierarchical patch dynamics. Patches are sites with unique environmental and functional characteristics that are discontinuously distributed in time and space within a lotic system. This distribution predicts that the occurrence of species will be based predominantly on their environmental requirements. We sampled three streams within the same drainage basin in the Brazilian Cerrado savanna, focusing on waterfalls and associated habitats (upstream, downstream), representing different functional zones. We collected 2,636 specimens representing six functional feeding groups (FFGs): brushers, collector-gatherers, collector-filterers, shredders, predators, and scrapers. The frequency of occurrence of these groups varied significantly among environments. This variation appeared to be related to the distinct characteristics of the different habitat patches, which led us to infer that the hierarchical patch dynamics model can best explain the distribution of functional feeding groups in minor lotic environments, such as waterfalls. PMID- 27193953 TI - Four New Species of Tetrigidae (Orthoptera). AB - Four new species of Tetrigidae (Orthoptera) from Anhui province, China, are described, namely Paragavialidium anhuiensis n. sp. of Scelimeninae, Bolivaritettix jinzhaiensis n. sp. of Metrodorinae, Bannatettix anhuiensis n. sp., and Formosatettix albomaculatus n. sp. of Tetriginae. PMID- 27193954 TI - Functional and Numerical Responses of Three Species of Predatory Phytoseiid Mites (Acari: Phytoseiidae) to Thrips flavidulus (Thysanoptera: Thripidae). AB - Phytoseiid mites are considered the most effective natural enemies of pest mites. They also have been shown to attack pest thrips. It is unknown, however, whether phytoseiid mites can reduce high densities of Thrips flavidulus (Bagnall). We addressed this question by the study of functional and numerical responses. The aim of this research was to evaluate the potential predation success of the adults of three predatory mites, Neoseiulus cucumeris (Oudemans), Neoseiulus barkeri (Hughes), and Euseius nicholsi (Ehara & Lee), against the first-instar of T. flavidulus in a climatic chamber at five different temperatures. The results showed that the functional responses of those predators reflected the Holling type II functional response and were density dependent and positively related to temperature. For the three predatory mites, predation and successful attack rates increased with increasing temperature up to 26 degrees C, reducing afterward. Handling time had the opposite trend. Reproductive ability also increased with an increase in temperature and prey consumption. PMID- 27193955 TI - Effects of Methanolic Extracts of Annona Species on the Development and Reproduction of Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae). AB - Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae) causes significant losses in corn crops and necessitates the use of alternative control strategies, such as the application of bioinsecticides. We report the effect of methanolic leaf extracts of Annona dioica, Annona cacans, and Annona coriacea on the development and reproduction of S. frugiperda. A quantitative analysis was carried out to determine the total concentration of phenolics, flavonoids, and condensed tannin (CT) in leaf extracts. Corn leaves were immersed in a 1% methanolic leaf extract solution and fed to second instars of S. frugiperda. Leaf disks dipped in the synthetic insecticide Connect(r) (Bayer CropScience Ltda) composed of a neonicotinoid (imidacloprid) and a pyrethroid (beta-cyfluthrin), which are harmful to S. frugiperda, was used as positive control. Distilled water was used as a negative control treatment. The leaf extract of A. coriacea decreased larval survivorship, arrested pupal development, and affected the weight gain of S. frugiperda. A. dioica also affected larval survivorship, but its effects were more pronounced for the adult stage, as fecundity, fertility, egg hatchability, and embryonic development were severely affected. Leaf extracts from A. cacans had no effect on S. frugiperda. The leaf extracts of A. dioica and A. coriacea showed a higher content of flavonoids and phenols, respectively. Our results indicated that both A. dioica and A. coriacea have the potential for development as botanical insecticides. PMID- 27193940 TI - Phytochemicals in Ischemic Stroke. AB - Stroke is the second foremost cause of mortality worldwide and a major cause of long-term disability. Due to changes in lifestyle and an aging population, the incidence of stroke continues to increase and stroke mortality predicted to exceed 12 % by the year 2030. However, the development of pharmacological treatments for stroke has failed to progress much in over 20 years since the introduction of the thrombolytic drug, recombinant tissue plasminogen activator. These alarming circumstances caused many research groups to search for alternative treatments in the form of neuroprotectants. Here, we consider the potential use of phytochemicals in the treatment of stroke. Their historical use in traditional medicine and their excellent safety profile make phytochemicals attractive for the development of therapeutics in human diseases. Emerging findings suggest that some phytochemicals have the ability to target multiple pathophysiological processes involved in stroke including oxidative stress, inflammation and apoptotic cell death. Furthermore, epidemiological studies suggest that the consumption of plant sources rich in phytochemicals may reduce stroke risk, and so reinforce the possibility of developing preventative or neuroprotectant therapies for stroke. In this review, we describe results of preclinical studies that demonstrate beneficial effects of phytochemicals in experimental models relevant to stroke pathogenesis, and we consider their possible mechanisms of action. PMID- 27193956 TI - Population Dynamics and Temperature-Dependent Development of Chrysomphalus aonidum (L.) to Aid Sustainable Pest Management Decisions. AB - The increasing worldwide trades progressively led to decreased impact of natural barriers on wild species movement. The exotic scale Chrysomphalus aonidum (L.) (Hemiptera: Diaspididae), recently reported on citrus in southern Italy, may represent a new threat to Mediterranean citriculture. We studied C. aonidum population dynamics under field conditions and documented its development under various temperatures. To enable describing temperature-dependent development through the use of linear and non-linear models, low temperature thresholds and thermal constants for each developmental stage were estimated. Chrysomphalus aonidum was able to perform four generations on green parts (leaves, sprouts) of citrus trees and three on fruits. In addition, an overall higher population density was observed on samples collected in the southern part of the tree canopy. Temperature had a significant effect on the developmental rate; female needed 625 degree days (DD) to complete its development, while male needed 833 DD. The low threshold temperatures, together with data from population dynamics, demonstrated that C. aonidum is able to overwinter as second instar and as an adult. The results obtained, validated by those collected in the field, revealed few differences between predicted and observed dates of first occurrence of each C. aonidum instar in citrus orchards. Data on C. aonidum phenology and the definition of the thermal parameters (lower and upper threshold temperatures, optimum temperature, and the thermal constant) by non-linear models could allow the estimation of the occurrence in the field of each life stage and would be helpful in developing effective integrated control strategies. PMID- 27193957 TI - Resistance of Citrus and Related Genera to Diaphorina citri Kuwayama (Hemiptera: Liviidae). AB - The present study was developed to evaluate the resistance of the following genotypes of Citrus and related genera to this pest: 'Pera,' 'Natal', and 'Washington Navel' oranges (Citrus sinensis), 'Marsh Seedless' grapefruit (Citrus paradisi), hardy orange 'Rubidoux' (Poncirus trifoliata), kumquat (Fortunella margarita Swingle), citrumelo 'Swingle' (C. paradisi x P. trifoliata), and citrange 'Troyer' (P. trifoliata x C. sinensis). The experiments were performed in greenhouses with plants grafted onto 'Rangpur' lime (Citrus limonia) and placed individually in voile cages. The preference for oviposition in a no-choice test, and the effect of genotype were evaluated. The egg-adult cycle was monitored to determine the effect of genotype on the biology of the insect. Poncirus 'Rubidoux' was the least preferred genotype for oviposition; reduced number of eggs was also found to occur on citrange 'Troyer', and 'Marsh Seedless' was the genotype with the most eggs. No significant variation in the duration of the embryonic period was observed; however, a difference in the viability of eggs was found, with the lowest egg viabilities on 'Swingle.' Kumquat and 'Marsh Seedless' genotypes were correlated with increased durations of the nymphal phase, however, there was no difference in the survival of this phase. Fecundity of females on 'Troyer', 'Swingle', and kumquat was reduced. Considering all of the evaluated parameters, it was concluded that cultivars of sweet orange are the most susceptible genotypes to Diaphorina citri. Regarding oviposition, P. trifoliata 'Rubidoux' showed resistance of the antixenosis type. PMID- 27193958 TI - Tropical Plant Extracts as Sources of Grain-Protectant Compounds Against Sitophilus zeamais Motschulsky (Coleoptera: Curculionidae). AB - The toxicity of organic plant extracts to Sitophilus zeamais Motschulsky (Coleoptera: Curculionidae) was assessed for three tropical plant species: branches, leaves, and seeds of Annona montana (Annonaceae), branches of Aristolochia paulistana (Aristolochiaceae), and leaves and branches of Casearia sylvestris (Salicaceae). The screening assay resulted that the extracts of A. montana seeds obtained with hexane (LC50 = 534.75 mg kg(-1) and LT50 = 6.10 days) and with dichloromethane (LC50 = 424.67 mg kg(-1) and LT50 = 5.03 days) were the most promising treatments, followed by the extract prepared from A. montana leaves with hexane (LC50 = 837.70 mg kg(-1) and LT50 = 4.90 days). Moreover, extracts (at 1,500 mg kg(-1)) prepared from C. sylvestris branches with dichloromethane and A. paulistana with hexane caused significant mortality (37% and 41.5%, respectively) beyond sublethal effects on S. zeamais. Therefore, based on the biological assays, extraction yield, and evaluation of the chromatographic profile of the crude extracts by TLC, the hexane extract of A. montana seeds was selected and fractioned using liquid-liquid partitioning. The hydroalcoholic fraction caused mortality of 55.5%, significantly superior to dichloromethane fraction, which caused 35.5% of mortality. Chemical analyses ((1)H NMR, HPLC, and TLC) were performed, and the results showed the presence of alkaloids and acetogenins in both active fractions, which have been associated with bioactivity. Therefore, extracts prepared from A. montana seeds (especially) is an interesting source of new compounds with promising grain-protectant properties. PMID- 27193959 TI - Influence of Substrate Color on Oviposition Behavior, Egg Hatchability, and Substance of Egg Origin in the Mosquito Anopheles sinensis (Wiedemann) (Diptera: Culicidae). AB - Understanding the factors that influence the choice of substrate for oviposition by the malaria mosquito is critical to efforts directed to the management of the disease and vector control measures aimed at modifications of larval habitat. The influence of black and white substrates on Anopheles sinensis (Wiedemann) (Culicidae: Anophelinae) female oviposition behavior and egg-hatching rate and the presence of substances associated with egg laying were studied. Results from the no-choice tests showed that the number of eggs laid on black substrate was significantly greater than that laid on white substrate. Results from the dual choice tests revealed that gravid females showed stronger preference for the black substrate than that for the white substrate. Furthermore, the egg-hatching rate on white substrate was significantly lower than that observed on black substrate. Results from the three-choice tests showed that substance of egg origin was associated with the black substrates (UBS) that were attractive for and stimulated oviposition. The results of this study suggest that there might be some compounds in the black substrates which play a positive role in the oviposition behavior of female mosquitoes and in the development of eggs and that eggs might produce and release active substances that attract females and stimulate oviposition. These results could be important as regards to the optimization of mosquitoes raised for experimental purposes and the control of malaria mosquitoes by altering the oviposition behavior of gravid females. PMID- 27193960 TI - Hadife, N., Nemos, C., Frippiat, J.-P., et al. Interleukin-24 mediates apoptosis in human B-cells through early activation of cell cycle arrest followed by late induction of the mitochondrial apoptosis pathway. Leuk. Lymphoma. 2013;54(3):587 597. http://tandfonline.com/doi/abs/10.3109/10428194.2012.717079. PMID- 27193961 TI - Lanthanide-Connecting and Lone-Electron-Pair Active Trigonal-Pyramidal-AsO3 Inducing Nanosized Poly(polyoxotungstate) Aggregates and Their Anticancer Activities. AB - By virtue of the stereochemical effect of the lone-electron pair located on the trigonal-pyramidal-AsO3 groups and the one-pot self-assembly strategy in the conventional aqueous solution, a series of novel lanthanide-bridging and lone electron-pair active trigonal-pyramidal-AsO3 inducing nanosized poly(polyoxotungstate) aggregates [H2N(CH3)2]6 Na24H16{[Ln10W16(H2O)30O50](B alpha-AsW9O33)8}.97H2O [Ln = Eu(III) (1), Sm(III) (2), Gd(III) (3), Tb(III) (4), Dy(III) (5), Ho(III) (6), Er(III) (7), Tm(III) (8)] were prepared and further characterized by elemental analyses, IR spectra, UV spectra, thermogravimetric (TG) analyses and single-crystal X-ray diffraction. The most remarkable structural feature is that the polyanionic skeleton of {[Ln10W16(H2O)30O50](B alpha-AsW9O33)8}(46-) is constructed from eight trivacant Keggin [B-alpha AsW9O33](9-) fragments through ten Ln centers and sixteen bridging W atoms in the participation of fifty extraneous oxygen atoms. Notably, 4 and 8 can be stable in the aqueous solution not only for eight days but also in the range of pH = 3.9 7.5. Moreover, the cytotoxicity tests of 4 and 8 toward human cervical cancer (HeLa) cells, human breast cancer (MCF-7) cells and mouse fibroblast (L929) cells were performed by the 3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and the cell apoptosis processes were characterized by calcein AM/PI staining experiments, annexin V-FITC/PI staining experiments and morphological changes. PMID- 27193962 TI - Irritable bowel syndrome and the perinatal period: lower birth weight increases the risk. AB - BACKGROUND: Early life events have been found to be associated with irritable bowel syndrome (IBS) suggesting a role in development of functional disorders. The study aim was to identify potential perinatal risk factors for adult IBS. METHODS: Utilizing a population-based nested case-control design, cases who met modified Rome III criteria for IBS and age- and-gender matched controls were identified using responses from prior mailed surveys to a random sample of Olmsted County residents. Medical records of eligible respondents were reviewed for perinatal events of interest. The association of early life events with subsequent case status was assessed using conditional logistic regression. KEY RESULTS: Of 3 417 respondents, 513 were born in Olmsted County and 108 met criteria for IBS. Due to missing records, 89 pairs were included in the final analyses. Logistic regression revealed only birth weight as a predictor of IBS. Lower birth weight increased the odds for IBS (OR = 1.54 [95% CI = (1.12, 2.08), p = 0.008]). Median birth weight was 3.35 kg (range: 1.96-5.24) and 3.57 kg (range: 2.18-4.59) for cases and controls, respectively. Maternal age, delivery method, and antibiotic exposure were not associated with IBS status but this study was only powered to detect large odds ratios. CONCLUSIONS AND INFERENCES: Lower birth weight was observed as a risk factor for IBS. It is not clear if in utero developmental delays directly lead to IBS or if low birth weight is a prospective marker for subsequent early life problems leading to IBS. PMID- 27193964 TI - Orthogonal dual-click diyne for CuAAC and/or SPAAC couplings. AB - Carbamate-tethered propargyl and benzocyclononyne moieties within a single molecular unit undergo cycloaddition with azides under complementary CuAAC and/or SPAAC coupling conditions. The carbamate linker can be cleaved by analogy to the CBz protecting group for click capture-and-release applications. PMID- 27193963 TI - Limited value of pro-inflammatory oxylipins and cytokines as circulating biomarkers in endometriosis - a targeted 'omics study. AB - Endometriosis is a common, complex gynecologic disorder characterized by the presence of endometrial-like tissues at extrauterine sites. Elevation in protein and lipid mediators of inflammation including oxylipins and cytokines within the peritoneum characterize the inflamed pelvic region and may contribute to the survival and growth of displaced endometrial tissues. The presence of a clinically silent but molecularly detectable systemic inflammation in endometriosis has been proposed. Thus, we examined serum oxylipin and immunomodulatory protein levels in 103 women undergoing laparoscopy to evaluate systematically any involvement in systemic pathophysiological inflammation in endometriosis. Oxylipin levels were similar between women with and without endometriosis. Stratification by menstrual phase or severity did not offer any difference. Women with ovarian endometriosis had significantly lower 12-HETE relative to peritoneal endometriosis (-50.7%). Serum oxylipin levels were not associated with pre-operative pain symptoms. Changes to immunomodulatory proteins were minimal, with IL-12(p70), IL-13 and VEGF significantly lower in mild endometriotic women compared to non-endometriotic women (-39%, -54% and -76% respectively). Verification using C-reactive protein as a non-specific marker of inflammation further showed similar levels between groups. The implications of our work suggest pro-inflammatory mediators in the classes studied may have potentially limited value as circulating biomarkers for endometriosis, suggesting of potentially tenuous systemic inflammation in endometriosis. PMID- 27193966 TI - Chronic perfluorooctanesulfonic acid exposure disrupts lipid metabolism in zebrafish. AB - Perfluorooctanesulfonic acid (PFOS), a ubiquitous contaminant, has been used in various industrial applications. Currently few studies have documented the effects of chronic PFOS exposure on lipid metabolism, especially in aquatic organisms. The present study defined the effects of chronic exposure to low level of PFOS on lipid metabolism in F0 adult zebrafish and F1 offspring. Our findings revealed a severe fatty degeneration in the liver of F0 males treated with 0.5 MUM PFOS and significant ultrastructure changes associated with substance transport or metabolism in liver and intestines (abnormal mitochondria and endoplasmic reticulum, disordered arrangement of inner microvilli within intracellular canaliculus). To address the potential trans-generational effects of PFOS exposure, the early gene expression related to lipid metabolism was measured by real-time quantitative polymerase chain reaction in F1 derived from chronically exposed parental fish. The results indicated that lepa (leptin alpha), kiss1 (kisspeptins), xdh (xanthine dehydrogenases), and insr (insulin receptor) were significantly upregulated in F1 while dgat1b (diacylglycerol O acyltransferase), hb9 (motor neuron/pancreas homeobox), and Apoa1 (apolipoprotein A-I) were downregulated. These findings provided evidence that PFOS chronic exposure adversely impacts lipid metabolism in both F0 and F1 and demonstrated the validity of using zebrafish as an alternative model for PFOS chronic toxicity screening. PMID- 27193967 TI - Effects of short-term glucocorticoid administration on bone mineral density, biomechanics and microstructure in rats' femur. AB - The effects of short-term use of oral glucocorticoid (GC) on the skeleton are not well defined. To address this gap, the influences of 7 days, 21 days of GC administration on femurs of intact rats were investigated. Forty 4-month-old female Sprague-Dawley rats were randomly divided into control group (Cont) and prednisone-treated group (Pre) and administered either distilled water or prednisone acetate at doses of 3.5 mg/kg/day for 0, 7 and 21 days, respectively. All the femurs were harvested for dual-energy X-ray absorptiometry scan, biomechanical testing and micro computed tomography scan. The whole body weight, femur bone mineral density (BMD), all three-point bending test parameters, microstructural parameters increased or improved significantly in Cont at day 21 when compared to day 0. The whole body weight, distal femur BMD, Young's modulus, bending stiffness, density of tissue volume and trabecular thickness (Tb.Th) decreased, while structure model index and trabecular separation (Tb.Sp) increased significantly in Pre at day 21 when compared to age-matched control but had no significant differences between day 7 and day 21. Our data demonstrate that 7-day use of prednisone does not influence on rats' femur, and 21-day use of prednisone slows in rate of whole body weight gain, decreases femur metaphysis BMD and bone stiffness which mainly due to the deteriorated bone microstructure. PMID- 27193965 TI - The trouble with 'Categories': Rethinking men who have sex with men, transgender and their equivalents in HIV prevention and health promotion. AB - This double Special Issue of Global Public Health presents a collection of articles that seek more adequately to represent sexual and gender diversities and to begin to rethink the relationship to HIV prevention and health promotion - in both the resource rich nations of the global North, as well as in the more resource constrained nations of the global South. Reckoning with the reality that today the global response to HIV has failed to respond to the needs of gay, bisexual and other men who have sex with men, and transgender persons, we turn our attention to processes and practices of categorisation and classification, and the entanglement of the multiple social worlds that constitute our understanding of each of these categories and people within the categories. Jointly, these articles provide critical perspectives on how defining and redefining categories may impact the conceptual frameworks and empirical evidence that inform global understandings of HIV infection, those communities most vulnerable, and our collective response to the evolving HIV epidemic. PMID- 27193968 TI - Disposable bipolar irrigated sealer (Aquamantys((r))) for liver resection: use with caution. AB - The disposable bipolar irrigated sealer has been demonstrated to reduce perioperative bleeding, but its role in preventing postoperative cut-surface complications has not been evaluated to date. A prospective observational study was performed between January and September 2013 to evaluate a disposable bipolar irrigated sealed (Aquamantys((r))) on a continuous series of 51 first liver resections without biliary reconstruction. Primary end-point was the occurrence of cut-surface complications during the postoperative period. Secondary endpoints were postoperative complications and the 1-year overall survival rate. The results were compared to a propensity score matched group of 153 liver resections performed with conventional monopolar cautery. A cut-surface complication occurred in 13/51 (25.5 %) resected patients. Bleeding, bile leakage and subphrenic abscess occurred in 7.8, 11.8 and 11.8 % patients, respectively. Compared to the matched group, the resected group had a higher rate of cut surface complications (25.5 vs. 14.7 %, p < 0.01) and a higher rate of Clavien Dindo type >=3 postoperative complications (29.5 vs. 17.2 %, p < 0.01). In the multivariate analysis, preoperative chemotherapy (p = 0.03, 95 % CI 1.09-5.9, OR 2.53), blood transfusion (p = 0.02, 95 % CI 1.78-6.55, OR 2.78) and Aquamantys((r)) use (p = 0.02, 95 % CI 1.21-6.7, OR 2.85) were independent of cut surface complications within the first 90 postoperative days. The overall 1-year survival rates were not different between the two groups (p = 0.078). Aquamantys((r)) use is associated with an increased rate of postoperative complications compared to classical monopolar cautery, and we recommend that it should be used with caution in this type of surgery. PMID- 27193970 TI - Residents'corner December 2013. Editorial: what's new this month? PMID- 27193969 TI - The bioactivities of the central segment of Zp2 polypeptide. AB - In order to understand the role of the protein zona pellucida 2 in fertilization, an antibody against a central segment of the zona pellucida 2 peptide, segment 190-505 (Z2eH), was prepared. The influence of the antibody on sperm-zona interaction was tested using the sperm-egg binding assay. The effect of the antibody on fertility was evaluated by passive immunization with anti-Z2eH antibody. Immunohistochemical assay showed that an antibody from rabbit reacted specifically with the natural zona pellucida on mouse ovarian sections. Immunofluorescence assay showed that the antibody bound specifically to the zonae pellucidae of the ovulated oocytes and 2-cell embryos after passive immunization. The antibody-treated oocytes bound capacitated sperm as control oocytes, passive immunization did not impede the action of sperm to fertilize the oocyte in vivo. These findings suggest that the central peptide of ZP2 (190-505) is immunogenic and contains zona pellucida-specific epitopes, however the central polypeptide might not be the crucial part from which to construct a functional domain to bind sperm. PMID- 27193972 TI - First Step Towards a Devil's Staircase in Spin-Crossover Materials. AB - The unprecedented bimetallic 2D coordination polymer {Fe[(Hg(SCN)3 )2 ](4,4' bipy)2 }n exhibits a thermal high-spin (HS)<->low-spin (LS) staircase-like conversion characterized by a multi-step dependence of the HS molar fraction gammaHS . Between the fully HS (gammaHS =1) and LS (gammaHS =0) phases, two steps associated with different ordering appear in terms of spin-state concentration waves (SSCW). On the gammaHS ~0.5 step, a periodic SSCW forms with a HS-LS-HS-LS sequence. On the gammaHS ~0.34 step, the 4D superspace crystallography structural refinement reveals an aperiodic SSCW, with a HS-LS sequence incommensurate with the molecular lattice. The formation of these different long-range spatially ordered structures of LS and HS states during the multi-step spin-crossover is discussed within the framework of "Devil's staircase"-type transitions. Spatially modulated phases are known in various types of materials but are uniquely related to molecular HS/LS bistability in this case. PMID- 27193973 TI - Prevalence of Irritable Bowel Syndrome-like Symptoms in Japanese Patients with Inactive Inflammatory Bowel Disease. AB - Background/Aims: Few studies are available that have investigated the risk factors for overlapping irritable bowel syndrome (IBS)-like symptoms in patients with inactive inflammatory bowel disease (IBD). The present study has 3 objectives: (1) to assess the prevalence of IBS-like symptoms in Japanese patients with inactive IBD using Rome III criteria, (2) to examine the relationship of IBS-like symptoms to health related quality of life (HR-QOL), and (3) to investigate associations for developing IBS-like symptoms in patients with inactive IBD. Methods: IBS-like symptoms were evaluated using the Rome III questionnaire for functional gastrointestinal disorders. HR-QOL and hospital anxiety and depression scale were evaluated. Results: IBS-like symptoms were found in 17.5% (7/40) of patients with inactive ulcerative colitis, 27.1% (29/107) of patients with inactive Crohn's disease (CD), and 5.3% (23/438) of healthy control subjects. The QOL level was significantly lower and anxiety score was significantly higher in inactive CD patients with IBS-like symptoms than in those without such symptoms (P = 0.003, P = 0.009). Use of anti-anxiety drugs was associated with the presence of IBS symptoms (P = 0.045). HR-QOL score was lower and anxiety score was higher in patients with inactive ulcerative colitis, but the difference was not statistically significant. Conclusions: The prevalence of IBS-like symptoms in inactive IBD patients was significantly higher than in healthy controls. Inactive CD patients with IBS-like symptoms has low QOL and anxiety; suggesting that anxiety may be associated with symptom development in such patients. PMID- 27193971 TI - ISG15 deficiency and increased viral resistance in humans but not mice. AB - ISG15 is an interferon (IFN)-alpha/beta-induced ubiquitin-like protein. It exists as a free molecule, intracellularly and extracellularly, and conjugated to target proteins. Studies in mice have demonstrated a role for Isg15 in antiviral immunity. By contrast, human ISG15 was shown to have critical immune functions, but not in antiviral immunity. Namely, free extracellular ISG15 is crucial in IFN gamma-dependent antimycobacterial immunity, while free intracellular ISG15 is crucial for USP18-mediated downregulation of IFN-alpha/beta signalling. Here we describe ISG15-deficient patients who display no enhanced susceptibility to viruses in vivo, in stark contrast to Isg15-deficient mice. Furthermore, fibroblasts derived from ISG15-deficient patients display enhanced antiviral protection, and expression of ISG15 attenuates viral resistance to WT control levels. The species-specific gain-of-function in antiviral immunity observed in ISG15 deficiency is explained by the requirement of ISG15 to sustain USP18 levels in humans, a mechanism not operating in mice. PMID- 27193974 TI - Laryngopharyngeal Reflux in Children with Chronic Otitis Media with Effusion. AB - BACKGROUND/AIMS: To evaluate the characteristic properties of laryngopharyngeal reflux (LPR) and gastroesophageal reflux (GER) in children with otitis media with effusion (OME) using 24-hour multichannel intraluminal impedance combined with dual-probe (pharyngeal and esophageal) pH-metry. METHODS: Children aged 7-10 years of age with OME underwent 24-hour multichannel intraluminal impedance pH metry. The upper pH sensor was situated 1 cm above the upper esophageal sphincter, and the lower pH sensor was placed 3-5 cm above the lower esophageal sphincter. Parents were asked to complete the gastroesophageal reflux assessment of symptoms in a pediatrics questionnaire. RESULTS: Twenty-eight children were enrolled; LPR was detected in 19 (67.9%) children. The criteria of the LPR diagnosis was the presence of at least one supraesophageal episode with a pH < 5.0 and a change in the pH value measured from the initial level at the upper sensor of > 0.2. In total, 64 episodes were observed. Assessment of all LPR episodes showed the presence of 246 episodes in the entire study. A considerable predominance of weakly acidic episodes (87.8%) was noted; there were 6.5% acidic episodes, and weakly alkaline episodes reached 5.7%. Pathological GER was noted in 10 (35.7%) subjects. Acid GER was detected in 8 children, 2 of whom demonstrated non-acidic reflux. In the LPR-negative patients, no pathological GER was confirmed with the exception of a single case of non-acidic reflux. CONCLUSIONS: LPR was frequently noted in the group of children with OME, and it might be an important risk factor in this common disease. PMID- 27193975 TI - A novel molecular disease classifier for psoriasis and eczema. AB - Novel specific therapies for psoriasis and eczema have been developed, and they mark a new era in the treatment of these complex inflammatory skin diseases. However, within their broad clinical spectrum, psoriasis and eczema phenotypes overlap making an accurate diagnosis impossible in special cases, not to speak about predicting the clinical outcome of an individual patient. Here, we present a novel robust molecular classifier (MC) consisting of NOS2 and CCL27 gene that diagnosed psoriasis and eczema with a sensitivity and specificity of >95% in a cohort of 129 patients suffering from (i) classical forms; (ii) subtypes; and (iii) clinically and histologically indistinct variants of psoriasis and eczema. NOS2 and CCL27 correlated with clinical and histological hallmarks of psoriasis and eczema in a mutually antagonistic way, thus highlighting their biological relevance. In line with this, the MC could be transferred to the level of immunofluorescence stainings for iNOS and CCL27 protein on paraffin-embedded sections, where patients were diagnosed with sensitivity and specificity >88%. Our MC proved superiority over current gold standard methods to distinguish psoriasis and eczema and may therefore build the basis for molecular diagnosis of chronic inflammatory skin diseases required to establish personalized medicine in the field. PMID- 27193977 TI - Beneficial effects of agomelatine in experimental model of sepsis-related acute kidney injury. AB - BACKGROUND: Sepsis-related acute kidney injury (AKI) is a serious complication of sepsis. Problems persist regarding early diagnosis and treatment of AKI. The aim of the present study was to evaluate the efficacy of agomelatine, which is primarily known for its positive effects on depressive and anxiety disorders in sepsis-related AKI. METHODS: Sepsis model was created with cecal ligation puncture (CLP). Rats were separated into 4 groups of 8 each: the control group, the sham-operated group, the CLP+saline group, and the CLP+agomelatine group. Agomelatine was administered intraperitoneally in doses of 20 mg/kg. RESULTS: In the agomelatine group, reductions were observed in levels of tumor necrosis factor alpha (TNF-alpha), malondialdehyde (MDA), blood urea nitrogen (BUN), and creatinine, as well as in histological kidney scores, compared to the non-treated group. In addition, it was demonstrated that agomelatine treatment had positive effect on sepsis-induced morphological damage to renal and tubular tissues. CONCLUSION: Agomelatine showed strong efficacy in sepsis-related AKI, demonstrated with histological and biochemical results in an experimental model. It is believed that antioxidant and pro-inflammatory effects of agomelatine are responsible for the improvement in kidneys. PMID- 27193976 TI - Role of alkaline phosphatase intestine-isomerase in acute mesenteric ischemia diagnosis. AB - BACKGROUND: The aim of the present study was to investigate the diagnostic value of alkaline phosphatase (ALP) intestine-isomerase, plasma lactate dehydrogenase (LDH), and D-dimer levels in acute mesenteric ischemia. METHODS: Thirty Wistar rats were divided into 5 groups of 6 rats each. In Group 1, blood samples were obtained to determine normal parameter levels. In the sham group, Group 2, blood samples were obtained following laparotomy. In Group 3, blood samples were obtained 2 hours after ligation. In Groups 4 and 5, blood samples were obtained at 4 and 6 hours after ligation, respectively. Ischemic damage was assessed using a pathological scoring system. Blood samples were analyzed for hourly changes in parameters. RESULTS: No statistically significant difference in D-dimer levels was found between ischemia groups (p=0.337). A statistically significant difference in LDH levels was found between the control group, Group 1, and Group 4 (p=0.018). ALP intestine-isomerase enzyme levels were not statistically significant in other groups (p=0.077). CONCLUSION: Findings indicate that plasma LDH levels higher than 1900 IU/L may be a useful marker in the early diagnosis of acute mesenteric obstruction. However, ALP intestine-isomerase enzyme and D-dimer plasma levels were not found to contribute to the diagnosis. PMID- 27193978 TI - Effects of different recruitment maneuvers on bacterial translocation and ventilator- induced lung injury. AB - BACKGROUND: Investigated in the present study were the effects of various recruitment maneuvers (RMs) using the same inflation pressure-time product on bacterial translocation from lung to blood, and ventilator-induced lung injury (VILI). METHODS: Tracheotomy was performed on anesthetized rats, and ventilation was initiated using pressure-controlled mode. Subsequently, Pseudomonas aeruginosa was inoculated through the tracheotomy tube and ventilated for 30 minutes before rats were randomly separated into 4 groups. Group 1 underwent sustained inflation (SI), Group 2 underwent low-pressure SI, Group 3 underwent modified sigh, and Group 4 was a control group. Blood cultures were taken at baseline, 15 minutes after randomization (after each RM for the first hour), and finally at 75 minutes after the last RM. The rats were euthanized and the lungs were extirpated. The left lung was taken for measurement of wet:dry weight ratio, and the right lung was used for pathologic evaluation. RESULTS: Positive blood cultures were found to be higher in Group 3 at early study periods. Total pathological scores were also higher in Group 3. CONCLUSION: Higher severity of ventilator-induced lung injury occurred in the modified sigh group, evidenced by bacterial translocation and results of histopathological evaluation. PMID- 27193979 TI - Neuroprotective effects of adalimumab on rats with experimental peripheral nerve injury: An electron microscopic and biochemical study. AB - BACKGROUND: Adalimumab, a new-generation anti-inflammatory agent, exerts its effect through tumor necrosis factor alpha (TNF-alpha), secreted from immune response cells such as macrophages and lymphocytes. TNF-alpha has been shown to play an important role in the processes of apoptosis and demyelination, and blockage of its activity may improve neural healing. Investigated in the present study is the probable neuroprotective influence of adalimumab in rats using a peripheral nerve injury model with biochemical and electron microscopic methods. METHODS: Forty adult Wistar albino rats were randomly divided into control, sciatic nerve trauma, low-dose adalimumab, and high-dose adalimumab groups. Six rats from each group were assigned biochemical microscopy, and 4 were assigned electron microscopy. Neural injury was induced with clip compression following dissection of sciatic nerves. Adalimumab was simultaneously injected. The rats were sacrificed after 2 weeks of adalimumab treatment. RESULTS: Nerve tissue lipid peroxidation values were found to be significantly decreased in both the low- and high-dose adalimumab treatment groups, compared to the group subjected only to sciatic nerve trauma. CONCLUSION: Results demonstrate that adalimumab is an effective neuroprotective agent for neural healing, particularly in the early phase. PMID- 27193980 TI - Is every intussusception treatment an emergency intervention or surgery? AB - BACKGROUND: Intussusception is the second most common cause of acute abdomen in children, following appendicitis. The aim of the present study was to evaluate the experience of the authors, in an effort to promote intussusception management, especially that of small bowel intussusception. METHODS: Records of intussusception diagnosed between July 2002 and September 2014 were evaluated in terms of patient age, sex, clinical findings, admission time, ultrasonographic findings, treatment methods, and outcomes. RESULTS: Eighty-one patients, 52 males and 29 females, were included (mean age: 10.6 months). Intussusceptions were ileocolic (IC) in 52 cases, ileoileal (IL) in 26, and jejunojejunal (JJ) in 3. Nineteen (23.5%) patients underwent surgery. Hydrostatic reduction was performed in 45 (55.5%) IC cases. Seventeen (21%) patients with small bowel intussusceptions (SBIs), measuring 1.8-2.3 cm in length, spontaneously reduced. All patients who underwent surgery had intussusceptums >=4 cm. Three of the 4 intestinal resection cases had history of abdominal surgery. CONCLUSION: If peritoneal irritation is present, patients with intussusception must undergo surgery. Otherwise, in patients with IC intussusception and no sign of peritoneal irritation, hydrostatic or pneumatic reduction is indicated. When this fails, surgery is the next step. SBIs free of peritoneal irritation and shorter than 2.3 cm tend to spontaneously reduce. For those longer than 4 cm, particularly in patients with history of abdominal surgery, spontaneous reduction is unlikely. PMID- 27193981 TI - Work-related injuries sustained by emergency medical technicians and paramedics in Turkey. AB - BACKGROUND: Evaluated in the present study were locations, descriptions, and results of work-related injuries (WRIs) sustained by emergency medical technicians (EMTs) and paramedics in Turkey's most crowded city, Istanbul. METHODS: After the present study had been accepted by the urban health authority, a questionnaire was emailed to the healthcare personnel of Istanbul's 195 ambulance stations. RESULTS: Included in the present study were the responses of 901 members of staff (660 EMTs and 241 paramedics), with a mean age of 29.5+/-6.1 (min: 18; max: 61). The majority of participants (94.9%) had encountered verbal abuse from the public, and 39.8% had encountered physical violence from patients' relatives. Levels of satisfaction with work in emergency medical services (EMS) was also evaluated, and 510 participants (57.6%) were unhappy. Regarding gender, female employees were more likely to be verbally attacked (p=0.01), while males were more likely to be physically attacked (p=0.001). It was reported that motor vehicle accidents (MVAs) were the most common cause of WRIs (81.4%), followed by needle-stick injuries (52.2%), ocular exposure to blood and other fluids (30.9%), and sharp injuries (22.5%). Only 10.5% (n=95) of WRIs were reported to authorities; 488 (54.2%) of participants just attended to the practice to prevent possible WRIs. CONCLUSION: For paramedics and EMTs, risk of WRI is obviously high. Strategies to decrease and prevent verbal and physical violence should be developed. PMID- 27193982 TI - Can outcome of pancreatic pseudocysts be predicted? Proposal for a new scoring system. AB - BACKGROUND: The spontaneous resolution rate of pancreatic pseudocysts (PPs) is 86%, and the serious complication rate is 3-9%. The aim of the present study was to develop a scoring system that would predict spontaneous resolution of PPs. METHODS: Medical records of 70 patients were retrospectively reviewed. Two patients were excluded. Demographic data and laboratory measurements were obtained from patient records. RESULTS: Mean age of the 68 patients included was 56.6 years. Female:male ratio was 1.34:1. Causes of pancreatitis were stones (48.5%), alcohol consumption (26.5%), and unknown etiology (25%). Mean size of PP was 71 mm. Pseudocysts disappeared in 32 patients (47.1%). With univariate analysis, serum direct bilirubin level (>0.95 mg/dL), cyst carcinoembryonic antigen (CEA) level (>1.5), and cyst diameter (>55 mm) were found to be significantly different between patients with and without spontaneous resolution. In multivariate analysis, these variables were statistically significant. Scores were calculated with points assigned to each variable. Final scores predicted spontaneous resolution in approximately 80% of patients. CONCLUSION: The scoring system developed to predict resolution of PPs is simple and useful, but requires validation. PMID- 27193983 TI - Diagnostic value of basic laboratory parameters for simple and perforated acute appendicitis: an analysis of 3392 cases. AB - BACKGROUND: The aim of the present study was to examine the efficacy of simple laboratory parameters including neutrophil-to-lymphocyte ratio (NLR), platelet count (PLT), mean platelet volume (MPV), and serum bilirubin level in the diagnosis of acute appendicitis and recognition of perforated appendicitis. METHODS: Records of 3392 patients who underwent appendectomy in a 10-year period were reviewed retrospectively. Patients were divided into 2 groups according to histopathological examination results: Group 1 had normal appendix, Group 2 had acute appendicitis. Patients with acute appendicitis were divided into subgroups: Group 2A had simple acute appendicitis, while Group 2B had perforated appendicitis. Efficacy of the aforementioned laboratory parameters was evaluated in the diagnosis of acute appendicitis and recognition of perforated appendicitis. Independent variables were determined by univariate analysis and multivariate analysis was performed. Receiver operating characteristic (ROC) curve analysis was used to identify significant parameters in multivariate analysis. Cut-off values, sensitivity, specificity, and accuracy calculations performed for parameters with area under curve (AUC) >0.600 were accepted as "significant parameters." RESULTS: White cell count (WCC), bilirubin, and NLR were significant parameters for the diagnosis of acute appendicitis. Cut-off values were 11900/mm3 for WCC (sensitivity: 71.2%; specificity: 67.2%; OR: 5.13), 1.0 mg/dl for bilirubin (sensitivity: 19.1%; specificity: 92.4%; OR: 2.96), and 3.0 for NLR (sensitivity: 81.2%; specificity: 53.1%; OR: 4.27). Serum bilirubin and NLR were independent variables for the diagnosis of perforated appendicitis. Cut-off values were 1.0 mg/dl for bilirubin (sensitivity: 78.4%; specificity: 41.7%; OR: 2.6) and 4.8 for NLR (sensitivity: 81.2%; specificity: 53.1%; OR: 2.6). CONCLUSION: Presence of at least 1 of the following findings in a patient suspected of having acute appendicitis was significantly associated with a definite diagnosis: WCC >11.900 mm3, serum bilirubin >1.0 mg/dl, NLR >3.0. In patients with acute appendicitis, serum bilirubin >1.0 mg/dl or NLR >4.8 were significantly associated with the presence of perforation. While WCC is a significant parameter for diagnosis of acute appendicitis, no significant association with perforated appendicitis was found. PLT and MPV were not useful parameters when diagnosing acute appendicitis. PMID- 27193984 TI - Neutrophil-lymphocyte ratio and mean platelet volume can be a predictor for severity of acute appendicitis. AB - BACKGROUND: Early diagnosis of perforation in acute appendicitis (AA) allows surgeons to select the most appropriate treatment. The aim of the present study was to determine whether preoperative neutrophil-lymphocyte ratio (NLR) and mean platelet volume (MPV) could predict perforation in AA. METHODS: Data collected from 413 consecutive patients with AA and 100 healthy controls were analyzed retrospectively. Patients were categorized as having had phlegmonous appendicitis, appendicitis with localized peritonitis, or appendicitis with perforation and/or gangrene. MPV and NLR values were compared among the control group and the 3 groups of patients with AA. RESULTS: Means values of MPV were 9.3+/-8 fL for the patient group and 8.5+/-0.9 fL for the healthy control group (p=0.0005). Mean values of MPV by patient subgroup were 8.8+/-5.8 for phlegmonous appendicitis, 8.9+/-5.8 for localized peritonitis, and 12.8+/-9.7 for appendicitis with perforation and/or gangrene (p=0.005). Cut-off value of MPV was set at 8.92 to differentiate AA with perforation and/or gangrene from other types of AA. Mean NLRs of patients with phlegmonous appendicitis, appendicitis with localized peritonitis, and appendicitis with perforation and/or gangrene were 8.3+/-5.6, 9.1+/-6.2, and 10.6+/-6.4, respectively; p=0.023. The cut-off value for NLR was set at 7.95 to differentiate AA with perforation and/or gangrene from other types of AA. CONCLUSION: Both NLR and MPV can be useful in predicting severity of AA. PMID- 27193985 TI - High velocity missile-related colorectal injuries: In-theatre application of injury scores and their effects on ostomy rates. AB - BACKGROUND: Treatment of colorectal injuries (CRIs) remains a significant cause of morbidity and mortality. The aim of the present study was to analyze treatment trends of Turkish surgeons and effects of the American Association for the Surgery of Trauma (AAST), Injury Severity (ISS), and Penetrating Abdominal Trauma Index (PATI) scoring systems on decision-making processes and clinical outcomes. METHODS: Data regarding high velocity missile (HVM)-related CRIs were retrospectively gathered. Four patient groups were included: Group 1 (stoma), Group 2 (no stoma in primary surgery), Group 2a (conversion to stoma in secondary surgery), and Group 2b (remaining Group 2 patients). RESULTS: Groups 1, 2, 2a, and 2b included 39 (66%), 20 (34%), 6 (30%), and 14 (70%) casualties, respectively. Ostomies were performed in casualties with significantly higher AAST scores (p<0.001). However, PATI and ISS scores were not decisive factors in the performance of ostomy (p=0.61; p=0.28, respectively). Ostomy rates of civilian and military surgeons were 62% and 68%, respectively (p=0.47). Receiver operating characteristic (ROC) analysis showed that AAST score was a more accurate guide for performing ostomy, with sensitivity and specificity rates of 80% and 92.9%, respectively. CONCLUSION: Clinical significance of diversion in HVM-related CRIs remains. Stomas were associated with lower complication rates and significantly higher AAST colon/rectum injury scores. PMID- 27193986 TI - Views of emergency physicians working in university and state hospitals in Turkey regarding the use of analgesics in patients with acute abdominal pain. AB - BACKGROUND: Use of narcotic analgesics in patients with acute abdominal pain does not cause delayed misdiagnosis, increases patient comfort and does not suppresses physical examination. The purpose of this study was to determine attitudes anddaily practices of emergency medicine (EM) specialists, residents and faculty members in Turkey on the use of analgesics in patients with acute abdominal pain and factors affecting their decisions on the use of analgesics. METHODS: A cross sectional study was performed between November 15, 2013 and January 25, 2014 by conducting a questionnaire to EM physicians working in University Hospitals, Education and Research Hospitals of the Ministry of Health, State Hospitals, and Private Hospitals in Turkey. RESULTS: A total of 803 questionnaires (participation rate: 47%) were completed. 59.3% (n=470) of the participants were research assistants. 49.5% of the participants reported that analgesic drugs "suppressed'' physical examination findings. They stated that 90% of the patients "always'' and "often'' requested analgesics and that 34.6% of surgery consultant physicians "rarely" recommended the use of analgesics, while 28.7% "never" recommended, and that there was no common policy established together with surgical departments (79.1%). According to the comparison between the EM specialists and residents, residents in the group stating that they would "never'' use analgesics were higher than specialists in number (p=0.002); residents reported that they administered analgesics "upon surgical intervention decision", while specialists reported that they administered analgesics "after patient's examination and treatment plan" (p=0.021); residents reported that analgesics "suppressed'' physical examination findings, while specialists reported that analgesics "clarified'' physical examination findings (p<0.0001); residents reported that they did not administer analgesics "before examination by surgeon'', while specialists reported otherwise (p=0.0001). Senior residents (>24 months) reported that they administered analgesics "often'' compared to junior residents (p=0.034) and that junior residents believed that the use of analgesics would "suppress physical examination findings'' at a higher percentage (p=0.002). CONCLUSION: The rates of use of analgesics in patients with acute abdominal pain by EM physicians are very low. The rates of use of analgesics by EM residents are much lower compared to EM specialists, and they highly believe that analgesic drugs suppress physical examination findings. Residents tend to administer analgesic drugs at a later stage. As seniority of residents increases, the rate of analgesics use and the opinion that analgesic drugs have no effect on physical examination findings increases. PMID- 27193988 TI - Triple gastric peptic ulcer perforation. AB - Patients with advanced or metastatic cancer have compromised nutritional, metabolic, and immune conditions. Nevertheless, little is known about gastroduodenal perforation in cancer patients. Described in the present report is the case of a 41-year old woman with stage IV recurrent laryngeal cancer, who used homeopathic anticancer therapy and who had triple peptic ulcer perforation (PUP) that required surgical repair. Triple gastric PUP is a rare complication. Self-administration of homeopathic anticancer medication should be strongly discouraged when evidence-based data regarding efficacy and toxicity is lacking. PMID- 27193987 TI - Intramedullary nailing of adult isolated diaphyseal radius fractures. AB - BACKGROUND: The aim of the present study was to evaluate functional and cosmetic outcomes of adult patients who underwent intramedullary nailing with newly designed intramedullary radius nails for isolated radius diaphyseal fractures. METHODS: Seventeen adult patients who had undergone intramedullary nailing for radius diaphyseal fractures were retrospectively evaluated. Patients with isolated radius diaphyseal closed fractures were included. Closed reduction was achieved in all patients. Wrist and elbow ranges of movement were calculated at final follow-up. Grip strength was calculated using a hydraulic hand dynamometer. Maximum radial bowing (MRB) and maximum radial bowing localization (MRBL) were calculated for treated and uninjured arms. Functional evaluation was performed using Grace-Eversman evaluation criteria and Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire score. RESULTS: Of the 17 patients with isolated radius diaphyseal fractures evaluated, 11 (64.7%) were male and 6 (35.3%) were female, with a mean age of 35.76 years (range: 23-61 years). Fractures were right sided in 11 (64.7%) and left-sided in 6 (35.3%) patients. Mean time to bone union was 10.2 weeks (range: 8-20 weeks). Mean supination was 75.35o (range: 67o-80o), pronation was 85.18o (range: 74o-90o). According to Grace-Eversman evaluation criteria, results were excellent in 16 (94%) and good in 1 (6%) patient. Mean DASH score was 12.58 (3.3-32.5). CONCLUSION: The gold-standard treatment of adult isolated radius diaphyseal fractures is plate and screw osteosynthesis. However, intramedullary nailing of isolated radius fractures is a good alternative treatment method, with excellent functional results and union rates similar to those of plate and screw osteosynthesis. PMID- 27193989 TI - Should warm fresh whole blood be the first choice in acute massive hemorrhage in emergency conditions? AB - Early management of rapid massive hemorrhage requires early administration of blood products and rapid surgical control of bleeding. Professionals in peripheral hospitals with limited resources often work under conditions similar to those in the military. Described in the present report are 3 cases in which warm fresh whole blood (WFWB) was used in patients with massive bleeding who presented to a peripheral hospital that had no blood products suitable for emergency conditions. Described first is the case of a 16-year-old female patient who underwent emergency cesarean section. The patient had massive bleeding from the uterus due to atony. Her hemoglobin (Hb) dropped to 3.5 g/dL. Six units of WFWB were transfused during surgery. Hemodynamic parameters and complete blood count (CBC) stabilized. She was transferred from the intensive care unit (ICU) to obstetrics on day 2 and was discharged on day 7. Described second is the case of a 35-year-old female patient who also underwent emergency cesarean section, and for whom massive bleeding was due to uterine atony. Hb dropped to 2 g/dL and hematocrit (HCT) to 5.4%. Nine units of WFWB were transfused, after which hemodynamic and laboratory parameters stabilized. The patient was extubated the following day, transferred from the ICU to obstetrics on day 3, and was discharged on day 8. Described third is the case of a 36-year-old male patient with stab injuries and hemorrhagic shock who underwent emergency surgery. The patient had injuries to the right renal artery and kidney. Nine units of WFWB were transfused due to continued hemorrhage during surgery. Following surgical control of bleeding and transfusion, hemodynamic parameters improved. The patient was transferred from the ICU on day 5 and discharged on day 10. WFWB transfusion nearly disappeared from civilian medicine after blood was separated into components, and whole blood is not usually available at blood banks. In massive transfusions, WFWB effectively replaces red blood cells (RBCs), platelets, plasma volume, and coagulation factors, while preventing hypothermia and dilutional coagulopathy. Blood components go through biochemical, biomechanical, and immunological changes during long storage, the duration of which affects both transfusion efficacy and associated risks. In the future, with the use of fast donor tests, fast ABO compatibility tests, platelet-sparing leukocyte filters, and developments in pathogen-decreasing technology, fresh whole blood (FWB) may be the first choice for massive transfusion. Future studies will reveal new procedures. PMID- 27193990 TI - A case of delayed carotid cavernous fistula after facial gunshot injury presented as loss of vision with symptom resolution after endovascular closure procedure. AB - Carotid cavernous fistulas (CCFs) are abnormal connections between the carotid artery and the cavernous sinus (CS), and can occur as a result of blunt and penetrating head injuries. While occurrence is rare, diagnosis can be made in the emergency department. Described in the present report is the case of a 26-year old man who presented with complaints of pain, redness, blurred and loss of vision in the right eye, and swelling of the upper face due to a gunshot injury he had sustained 35 days prior. PMID- 27193991 TI - A different approach to simultaneously injured ulnar and radial arteries: Translocation of an arterial segment. AB - Upper-extremity arterial injury is a common and serious condition that may lead to amputation if improperly treated. Ligation of the ulnar or radial artery is frequently performed by vascular surgeons as a method of treatment, which should be avoided, particularly if the radial and ulnar arteries were both injured. A different approach to reconstruction is described in the present report. PMID- 27193992 TI - Permanent resident. AB - The training of physicians in the past century was based primarily on responsibility and the chain-of-command. Those with the bulk of that responsibility in the fields of pediatrics and internal medicine were residents. Residents trained the medical students and supervised them carefully in caring for patients. Most attending physicians supervised their teams at arm's length, primarily serving as teachers of the finer points of diagnosis and treatment during set periods of the day or week with a perfunctory signature on write-ups or progress notes. Residents endeavored to protect the attending physician from being heavily involved unless they were unsure about a clinical problem. Before contacting the attending physician, a more senior resident would be called. Responsibility was the ultimate teacher. The introduction of diagnosis-related groups by the federal government dramatically changed the health care delivery system, placing greater emphasis on attending physician visibility in the medical record, ultimately resulting in more attending physician involvement in day-to day care of patients in academic institutions. Without specified content in attending notes, hospital revenues would decline. Although always in charge technically, attending physicians increasingly have assumed the role once dominated by the resident. Using biographical experiences of more than 40 years, the author acknowledges and praises the educational role of responsibility in his own training and laments its declining role in today's students and house staff. PMID- 27193993 TI - Deferasirox AUC efficacy cutoff and role of pharmacogenetics. PMID- 27193994 TI - Synthesis of the Cortistatin Pentacyclic Core by Alkoxide-Directed Metallacycle Mediated Annulative Cross-Coupling. AB - The pentacyclic core skeleton of the cortistatins has been prepared in a stereoselective fashion by strategic use of an alkoxide-directed metallacycle mediated annulative cross-coupling. This metal-centered tandem reaction delivers a polyunsaturated hydrindane and establishes the C13 stereodefined quaternary center with high levels of stereocontrol. Subsequent regio- and stereoselective global hydroboration results in the realization of the DE-trans ring fusion and a tertiary alcohol at C8. Establishment of the ABC-tricyclic subunit was then accomplished through phenolic oxidation/trans-acetalization, chemoselective reduction, regioselective cleavage, and intramolecular alkylation at C5. PMID- 27193995 TI - Predictors of a negative labour and birth experience based on a national survey of Canadian women. AB - BACKGROUND: A negative birth experience has been shown to have a significant impact on the well-being and future choices of mothers. The objective of this study was to assess the prevalence of, and identify the risk factors associated with a negative birth experience for women in Canada. METHODS: The study was based on secondary data analysis of the Maternity Experiences Survey (MES), a Canadian population database administered to 6,421 Canadian women in 2006. The examined outcome - negative birth experience - was derived from mothers' self report of overall labour and birth experience. Independent variables were maternal demographics, health characteristics, pregnancy-related characteristics, and birth characteristics. Multivariable logistic regression analysis was performed to determine the significant predictors of negative birth experience. Adjusted Odds Ratios (AOR) and 95 % Confidence Intervals (CI) are reported. RESULTS: Negative birth experience was reported among 9.3 % of women. The main significant predictors of a negative birth experience included older age (AOR 2.29, 95 % CI, 1.03-5.07), violence experienced in the past two years (AOR, 1.62, 95 % CI, 1.21-2.18), poor self-perceived health (adjusted OR, 1.95, 95 % CI, 1.36 2.80), prenatal classes attended (adjusted OR, 1.36, 95 % CI, 1.06-1.76), unintended pregnancy (adjusted OR, 1.30, 95 % CI, 1.03-1.63), caesarean birth (AOR, 1.65, 95 % CI, 1.32-2.06), and neonate admission to intensive care (AOR, 1.40, 95 % CI, 1.08-1.82). CONCLUSION: Significant predictors of a negative labour and birth experience were identified through this study, a first in the Canadian context. These findings suggest future research directions and provide a basis for the design and evaluation of maternal health policy and prevention programs. PMID- 27193996 TI - Role of the Polymerase epsilon sub-unit DPB2 in DNA replication, cell cycle regulation and DNA damage response in Arabidopsis. AB - Faithful DNA replication maintains genome stability in dividing cells and from one generation to the next. This is particularly important in plants because the whole plant body and reproductive cells originate from meristematic cells that retain their proliferative capacity throughout the life cycle of the organism. DNA replication involves large sets of proteins whose activity is strictly regulated, and is tightly linked to the DNA damage response to detect and respond to replication errors or defects. Central to this interconnection is the replicative polymerase DNA Polymerase epsilon (Pol epsilon) which participates in DNA replication per se, as well as replication stress response in animals and in yeast. Surprisingly, its function has to date been little explored in plants, and notably its relationship with DNA Damage Response (DDR) has not been investigated. Here, we have studied the role of the largest regulatory sub-unit of Arabidopsis DNA Pol epsilon: DPB2, using an over-expression strategy. We demonstrate that excess accumulation of the protein impairs DNA replication and causes endogenous DNA stress. Furthermore, we show that Pol epsilon dysfunction has contrasting outcomes in vegetative and reproductive cells and leads to the activation of distinct DDR pathways in the two cell types. PMID- 27193997 TI - SPATIAL: A System-level PAThway Impact AnaLysis approach. AB - The goal of pathway analysis is to identify the pathways that are significantly impacted when a biological system is perturbed, e.g. by a disease or drug. Current methods treat pathways as independent entities. However, many signals are constantly sent from one pathway to another, essentially linking all pathways into a global, system-wide complex. In this work, we propose a set of three pathway analysis methods based on the impact analysis, that performs a system level analysis by considering all signals between pathways, as well as their overlaps. Briefly, the global system is modeled in two ways: (i) considering the inter-pathway interaction exchange for each individual pathways, and (ii) combining all individual pathways to form a global, system-wide graph. The third analysis method is a hybrid of these two models. The new methods were compared with DAVID, GSEA, GSA, PathNet, Crosstalk and SPIA on 23 GEO data sets involving 19 tissues investigated in 12 conditions. The results show that both the ranking and the P-values of the target pathways are substantially improved when the analysis considers the system-wide dependencies and interactions between pathways. PMID- 27194000 TI - Mechanisms of charge accumulation in the dark operation of perovskite solar cells. AB - In this work, a new current peak at forward bias in the dark current-voltage curves has been identified for standard mesoscopic perovskite solar cells. This characteristic peak appears only under some specific conditions, mainly in the reverse scan (RS) direction and when the solar cells were kept for several seconds under short-circuit conditions before starting the RS measurement. This peak disappears when the above experimental conditions are not applied. It is considered that this uncommon diode shape is obtained because shallow and/or deep trap states located at the interface between either perovskite/p-type or perovskite/n-type transport materials are dynamically filled during the RS voltage scan. To corroborate this hypothesis, the response of hole transport materials (HTMs), small molecule spiro-OMeTAD and polymer P3HT, as well as both HTMs with additives, was compared. Also perovskite absorbers such as CH3NH3PbI3 and all-inorganic perovskite based on cesium (CsPbI3) were also analyzed, achieving in all cases similar trends. PMID- 27193999 TI - The cytosolic Fe-S cluster assembly component MET18 is required for the full enzymatic activity of ROS1 in active DNA demethylation. AB - DNA methylation patterns in plants are dynamically regulated by DNA methylation and active DNA demethylation in response to both environmental changes and development of plant. Beginning with the removal of methylated cytosine by ROS1/DME family of 5-methylcytosine DNA glycosylases, active DNA demethylation in plants occurs through base excision repair. So far, many components involved in active DNA demethylation remain undiscovered. Through a forward genetic screening of Arabidopsis mutants showing DNA hypermethylation at the EPF2 promoter region, we identified the conserved iron-sulfur cluster assembly protein MET18. MET18 dysfunction caused DNA hypermethylation at more than 1000 loci as well as the silencing of reporter genes and some endogenous genes. MET18 can directly interact with ROS1 in vitro and in vivo. ROS1 activity was reduced in the met18 mutant plants and point mutation in the conserved Fe-S cluster binding motif of ROS1 disrupted its biological function. Interestingly, a large number of DNA hypomethylated loci, especially in the CHH context, were identified from the met18 mutants and most of the hypo-DMRs were from TE regions. Our results suggest that MET18 can regulate both active DNA demethylation and DNA methylation pathways in Arabidopsis. PMID- 27193998 TI - Synergy between NMR measurements and MD simulations of protein/RNA complexes: application to the RRMs, the most common RNA recognition motifs. AB - RNA recognition motif (RRM) proteins represent an abundant class of proteins playing key roles in RNA biology. We present a joint atomistic molecular dynamics (MD) and experimental study of two RRM-containing proteins bound with their single-stranded target RNAs, namely the Fox-1 and SRSF1 complexes. The simulations are used in conjunction with NMR spectroscopy to interpret and expand the available structural data. We accumulate more than 50 MUs of simulations and show that the MD method is robust enough to reliably describe the structural dynamics of the RRM-RNA complexes. The simulations predict unanticipated specific participation of Arg142 at the protein-RNA interface of the SRFS1 complex, which is subsequently confirmed by NMR and ITC measurements. Several segments of the protein-RNA interface may involve competition between dynamical local substates rather than firmly formed interactions, which is indirectly consistent with the primary NMR data. We demonstrate that the simulations can be used to interpret the NMR atomistic models and can provide qualified predictions. Finally, we propose a protocol for 'MD-adapted structure ensemble' as a way to integrate the simulation predictions and expand upon the deposited NMR structures. Unbiased MUs scale atomistic MD could become a technique routinely complementing the NMR measurements of protein-RNA complexes. PMID- 27194003 TI - Rapid Absorption of Dry-Powder Intranasal Oxytocin. AB - PURPOSE: To probe the suitability of a dry-powder oxytocin formulation containing a carrier (MUcoTM; SNBL, Ltd.) for intranasal (IN) administration to treat post partum hemorrhage in the developing world. Specifically, to investigate (1) whether IN administration can achieve rapid systemic absorption in cynomolgus monkeys, and (2) whether the formulation exhibits sufficient physical and chemical stability. This study was conducted to support Merck for Mothers, Merck's 10-year global initiative to end preventable maternal deaths. METHODS: A partial-crossover pharmacokinetic (PK) study in cynomolgus monkeys (n = 6) was utilized to compare in vivo absorption of dry-powder IN oxytocin at three dose levels against an IM injection of an aqueous oxytocin formulation. Particle size distribution, delivered dose and chemical assay were monitored over a 12 month stability study. RESULTS: IN administration of oxytocin resulted in short (5 min) Tmax and good dose linearity in AUC and Cmax over the dose range tested (10-80 IU per animal). The relative bioavailability (BA) of IN oxytocin to IM injection was approximately 12%. The 80 IU formulation exhibited good physical stability and consistent dosing. After 12 months at 30 degrees C/65%RH, pouched samples retained 86.0% of their original assay value. CONCLUSIONS: The PK and stability data suggests that IN administration of oxytocin formulated in the MUcoTM carrier may represent a viable option for rapid systemic absorption in humans and a product compatible with resource-scarce regions. PMID- 27194002 TI - Emergence of 3D Printed Dosage Forms: Opportunities and Challenges. AB - The recent introduction of the first FDA approved 3D-printed drug has fuelled interest in 3D printing technology, which is set to revolutionize healthcare. Since its initial use, this rapid prototyping (RP) technology has evolved to such an extent that it is currently being used in a wide range of applications including in tissue engineering, dentistry, construction, automotive and aerospace. However, in the pharmaceutical industry this technology is still in its infancy and its potential yet to be fully explored. This paper presents various 3D printing technologies such as stereolithographic, powder based, selective laser sintering, fused deposition modelling and semi-solid extrusion 3D printing. It also provides a comprehensive review of previous attempts at using 3D printing technologies on the manufacturing dosage forms with a particular focus on oral tablets. Their advantages particularly with adaptability in the pharmaceutical field have been highlighted, which enables the preparation of dosage forms with complex designs and geometries, multiple actives and tailored release profiles. An insight into the technical challenges facing the different 3D printing technologies such as the formulation and processing parameters is provided. Light is also shed on the different regulatory challenges that need to be overcome for 3D printing to fulfil its real potential in the pharmaceutical industry. PMID- 27194005 TI - Freezing of gait: A rare delayed complication of whole brain radiation. PMID- 27194004 TI - Impact of Valve Morphology on the Prevalence of Coronary Artery Disease: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Literature studies suggested a lower prevalence of coronary artery disease (CAD) in bicuspid aortic valve (BAV) than in tricuspid aortic valve (TAV) patients. However, this finding has been challenged. We performed a meta-analysis to assess whether aortic valve morphology has a different association with CAD, concomitant coronary artery bypass grafting (CABG), and postoperative mortality. METHODS AND RESULTS: Detailed search was conducted according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guideline to identify all patients with BAV or TAV and presence of CAD, concomitant myocardial surgical revascularization, and the postoperative mortality. Thirty-one studies on 3017 BAV and 4586 TAV patients undergoing aortic valve surgery were included. BAV patients showed a lower prevalence of CAD (odds ratio [OR]: 0.33; 95% CI: 0.17, 0.65), concomitant CABG (OR, 0.45; 95% CI: 0.35, 0.59), and postoperative mortality (OR, 0.62; 95% CI: 0.40, 0.97) than TAV. However, BAV subjects were significantly younger than TAV (mean difference: -7.29; 95% CI: -11.17, -3.41) were more frequently males (OR, 1.61; 95% CI: 1.33, 1.94) and exhibited a lower prevalence of hypertension (OR, 0.58; 95% CI: 0.39, 0.87) and diabetes (OR, 0.71; 95% CI: 0.54, 0.93). Interestingly, a metaregression analysis showed that younger age and lower prevalence of diabetes were associated with lower prevalence of CAD (Z value: -3.03; P=0.002 and Z value: -3.10; P=0.002, respectively) and CABG (Z value: -2.69; P=0.007 and Z value: -3.36; P=0.001, respectively) documented in BAV patients. CONCLUSIONS: Analysis of raw data suggested an association of aortic valve morphology with prevalence of CAD, concomitant CABG, and postoperative mortality. Interestingly, the differences in age and diabetes have a profound impact on prevalence of CAD between BAV and TAV. In conclusion, our meta-analysis suggests that the presence of CAD is independent of aortic valve morphology. PMID- 27194007 TI - A possible method for in situ nitrogen removal in landfills by microbial-pumping iron behavior. AB - Nitrogen pollution from landfills needs urgent treatment. A batch experiment was designed to explore the possible in situ nitrogen removal in landfills based on the hypothesis of microbial-pumping-iron behavior, namely anaerobic microbial iron oxidation and reduction. The results confirm that a simultaneous Fe(ii) oxidation, accompanied by nitrate (NO3(-)-N) reduction and dissimilatory Fe(iii) reduction, can happen in aged municipal solid waste (AMSW). This phenomenon can last at least 10 years after landfilling. Organics is an important intermediate medium in that process. The dynamic anaerobic Fe redox cycle has the potential of denitrification without ammonia nitrogen (NH4(+)-N) accumulation. AMSW with deposited ages of 1-3 years is a good choice to enhance this redox cycle behavior coupled with denitrification. Conversely, AMSW with longer deposited ages (8-10 years) has a quicker iron cycle and a smaller NH4(+)-N accumulation. This suggests a possible method for in situ nitrogen removal in landfills. PMID- 27194009 TI - How to stop breathing: On the matter of getting respiratory motion under control. PMID- 27194008 TI - Inflammatory biomarkers and risk of cancer in 84,000 individuals from the general population. AB - Inflammation and cancer are tightly linked. This study tests the hypothesis that an inflammatory score based on plasma levels of C-reactive protein (CRP) and fibrinogen and whole blood leukocyte count is associated with risk of colorectal, lung, breast and prostate cancer. A score ranging from none through three elevated biomarkers was constructed in 84,000 individuals from the Danish general population. During a median follow-up time of 4.8 years, 4,081 incident cancers occurred. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) of incident cancer. Multifactor-adjusted HRs for colorectal cancer were 1.28 (95% CI, 1.01 to 1.62), 1.79 (95% CI, 1.41 to 2.27) and 2.18 (95% CI, 1.67 to 2.86) for individuals with elevated levels of one, two and three inflammatory biomarkers compared to individuals with none elevated biomarkers. A similar stepwise increasing risk was observed for lung and breast cancer with HRs of 3.03 (95% CI, 2.25 to 4.08) and 1.42 (95% CI, 1.11 to 1.80) for three versus none elevated biomarkers. HRs were highest within the first years of follow-up. Absolute 5-year risk of lung cancer was 7.8 (95% CI, 6.1 to 10)% among older smokers with three elevated biomarkers compared to 3.8 (95% CI, 2.6 to 5.6)% among those with none elevated biomarkers. In conclusion, simultaneously elevated CRP, fibrinogen and leukocyte count are associated with an increased risk of colorectal, lung and breast cancer. Cancer as a promoter of inflammation may be more likely to account for our findings than low-grade inflammation promoting cancer development. PMID- 27194006 TI - Development and evaluation of two subunit vaccine candidates containing antigens of hepatitis E virus, rotavirus, and astrovirus. AB - Hepatitis E virus (HEV), rotavirus (RV), and astrovirus (AstV) are important pathogens that transmit through a common fecal-oral route, causing hepatitis (HEV) and gastroenteritis (RV and AstV) respectively in humans. In this study, we developed and evaluated two subunit vaccine candidates that consisted of the same protruding or spike protein antigens of the three viruses in two formats, a fusion of the three antigens into one molecule (fused vaccine) vs. a mixture of the three free antigens together (mixed vaccine). Both vaccines were easily made via E. coli expression system. Mouse immunization experiments showed that the fused vaccine elicited significantly higher antibody responses against the three viral antigens than those induced by the mixed vaccine. In addition, the mouse post-immune antisera of the fused vaccine revealed significantly higher neutralizing titers against HEV infection in cell culture, as well as significantly higher 50% blocking titers (BT50) against RV VP8-HBGA receptor interactions than those of the post-immune antisera after immunization of the mixed vaccine. Thus, the fused vaccine is a promising trivalent vaccine candidate against HEV, RV, and AstV, which is worth for further development. PMID- 27194010 TI - Imaging the heart's brain: Simultaneous innervation/perfusion analysis in the era of new CZT cameras. PMID- 27194011 TI - Time course of large ribosomal subunit assembly in E. coli cells overexpressing a helicase inactive DbpA protein. AB - DbpA is a DEAD-box RNA helicase implicated in Escherichia coli large ribosomal subunit assembly. Previous studies have shown that when the ATPase and helicase inactive DbpA construct, R331A, is expressed in E. coli cells, a large ribosomal subunit intermediate accumulates. The large subunit intermediate migrates as a 45S particle in a sucrose gradient. Here, using a number of structural and fluorescent assays, we investigate the ribosome profiles of cells lacking wild type DbpA and overexpressing the R331A DbpA construct. Our data show that in addition to the 45S particle previously described, 27S and 35S particles are also present in the ribosome profiles of cells overexpressing R331A DbpA. The 27S, 35S, and 45S independently convert to the 50S subunit, suggesting that ribosome assembly in the presence of R331A and the absence of wild-type DbpA occurs via multiple pathways. PMID- 27194012 TI - Sequential use of the STICS crop model and of the MACRO pesticide fate model to simulate pesticides leaching in cropping systems. AB - The current challenge in sustainable agriculture is to introduce new cropping systems to reduce pesticides use in order to reduce ground and surface water contamination. However, it is difficult to carry out in situ experiments to assess the environmental impacts of pesticide use for all possible combinations of climate, crop, and soils; therefore, in silico tools are necessary. The objective of this work was to assess pesticides leaching in cropping systems coupling the performances of a crop model (STICS) and of a pesticide fate model (MACRO). STICS-MACRO has the advantage of being able to simulate pesticides fate in complex cropping systems and to consider some agricultural practices such as fertilization, mulch, or crop residues management, which cannot be accounted for with MACRO. The performance of STICS-MACRO was tested, without calibration, from measurements done in two French experimental sites with contrasted soil and climate properties. The prediction of water percolation and pesticides concentrations with STICS-MACRO was satisfactory, but it varied with the pedoclimatic context. The performance of STICS-MACRO was shown to be similar or better than that of MACRO. The improvement of the simulation of crop growth allowed better estimate of crop transpiration therefore of water balance. It also allowed better estimate of pesticide interception by the crop which was found to be crucial for the prediction of pesticides concentrations in water. STICS-MACRO is a new promising tool to improve the assessment of the environmental risks of pesticides used in cropping systems. PMID- 27194013 TI - Oil exploitation and its socioeconomic effects on the Niger Delta region of Nigeria. AB - The oil exploration and exploitation industry which is majorly centred in the Niger Delta region is without doubt currently the most important earner of foreign exchange to the Nigerian economy. The Niger Delta is home to an extraordinary variety of people; mostly fishers and farmers with a history of rich cultural heritage. However, the region is suffering from devastating oil pollution. Although the effects of oil spill depend on factors such as size or area of spill and geographical location, the socioeconomic and environmental costs of oil production can be extensive; these range from destruction of wildlife, biodiversity loss, air and water pollution, degradation of farmland and damage to aquatic ecosystems. The paper reviews the adverse effects of oil exploitation on the Niger Delta region. It researches the common belief that government and oil multinationals are negatively disposed to the socioeconomic and environmental wellbeing of host communities especially in events of oil spillage. The paper reveals that oil exploitation has increased the rate of environmental degradation and has perpetuated food insecurity as a result of death of fish and crops as well as loss of farm lands and viable rivers for fishing activities leading to loss of livelihood. The paper supports the call for multinationals operating in the region to modernise operating infrastructure and equipment in order to prevent avoidable oil spillages that often lead to community restiveness, and more so, intensification of joint efforts between oil multinationals and government in the capital development of the region is very important. PMID- 27194015 TI - Accumulation of metals relevant for agricultural contamination in gills of European chub (Squalius cephalus). AB - The study of metal bioaccumulation in the gills of European chub (Squalius cephalus) was conducted in September 2009 at the medium-sized rural river Sutla, characterized by agricultural and municipal type of water contamination. The concentration ranges were established for the first time in the soluble, metabolically available fractions of chub gills for 12 metals, which are environmentally extremely relevant and yet only seldom studied, as follows in a decreasing order: K, 225-895 mg L(-1); Na, 78-366 mg L(-1); Ca, 19-62 mg L(-1); Mg, 13-47 mg L(-1); Rb, 164-1762 MUg L(-1); Sr, 24-81 MUg L(-1); Ba, 13-67 MUg L( 1); Mo, 1.3-16 MUg L(-1); Co, 0.7-2.7 MUg L(-1); Li, 0.4-2.2 MUg L(-1); Cs, 0.2 1.9 MUg L(-1); and V, 0.1-1.8 MUg L(-1). The concentrations of Fe (1.6-6.4 mg L( 1)) and Mn (16-69 MUg L(-1)) were also determined and were in agreement with previous reports. By application of general linear modelling, the influence of different abiotic (metal exposure level) and biotic parameters (fish sex, age, size and condition) on metal bioaccumulation was tested. It was established that bioaccumulation of many metals in fish depended on various physiological conditions, wherein Ba could be singled out as metal exhibiting the strongest association with one of biotic parameters, being significantly higher in smaller fish. However, it was also undoubtedly demonstrated that the concentrations of three metals can be applied as reliable indicators of metal exposure even in the conditions of low or moderate water contamination, such as observed in the Sutla River, and those were nonessential elements Li and Cs and essential element Fe. The results of our study present an important contribution to maintenance of high ecological status of European freshwaters, through enrichment of knowledge on the bioaccumulation of various metals in gills of European chub as frequently applied bioindicator species in monitoring of water pollution. PMID- 27194016 TI - Evaluation of the microbiological quality of reclaimed water produced from a lagooning system. AB - The use of lagooning as a complementary natural method of treating secondary effluents of wastewater treatment plants has been employed as an affordable and easy means of producing reclaimed water. However, using reclaimed water for some purposes, for example, for food irrigation, presents some risks if the effluents contain microbial pathogens. Classical bacterial indicators that are used to assess faecal contamination in water do not always properly indicate the presence of bacterial or viral pathogens. In the current study, the presence of faecal indicator bacteria (FIB), heterotrophic bacterial counts (HBC), pathogens and opportunistic pathogens, such as Legionella spp., Aeromonas spp., Arcobacter spp., free-living amoeba (FLA), several viral indicators (human adenovirus and polyomavirus JC) and viral pathogens (noroviruses and hepatitis E virus) were analysed for 1 year in inlet and outlet water to assess the removal efficiency of a lagooning system. We observed 2.58 (1.17-4.59) and 1.65 (0.15-3.14) log reductions in Escherichia coli (EC) and intestinal enterococci (IE), respectively, between the inlet and outlet samples. Genomic copies of the viruses were log reduced by 1.18 (0.24-2.93), 0.64 (0.12-1.97), 0.45 (0.04-2.54) and 0.72 (0.22-2.50) for human adenovirus (HAdV), JC polyomavirus (JCPyV) and human noroviruses (NoV GI and GII), respectively. No regrowth of opportunistic pathogens was observed within the system. FLA, detected in all samples, did not show a clear trend. The reduction of faecal pathogens was irregular with 6 out of 12 samples and 4 out of 12 samples exceeding the EC and IE values, specified in the Spanish legislation for reclaimed water (RD 1620/2007). This data evidences that there is a need for more studies to evaluate the removal mechanisms of lagooning systems in order to optimize pathogen reduction. Moreover, surveillance of water used to irrigate raw edible vegetables should be conducted to ensure the fulfilment of the microbial requirements for the production of safe reclaimed water. PMID- 27194017 TI - Seafood consumption among Chinese coastal residents and health risk assessment of heavy metals in seafood. AB - The aims of the present study were to obtain the seafood dietary patterns of coastal residents, to determine the concentrations of heavy metals, and to evaluate the possible health risks caused by seafood intake. The daily food intakes of 24 types of seafood were collected from 738 participants from Xiamen, a southern Chinese coastal city, using food frequency questionnaire (FFQ) and dietary history method. One hundred and fifty-six samples of 14 types of highest intake seafood were collected from local markets for lead (Pb), cadmium (Cd), chromium (Cr), mercury (Hg), and arsenic (As) determination. Health risks via seafood consumption were evaluated by calculating the target hazard quotient (THQ) and the total hazard index (HI) for carcinogenic and non-carcinogenic effects recommended by the US Environmental Protection Agency. The results showed that the seafood daily intake of Xiamen residents was 61.5 (2.14, 115) g/day. The concentrations of Pb, Cd, Cr, Hg, and As in seafood were ND-0.45 mg/kg, ND-0.19 mg/kg, ND-0.80 mg/kg, ND-0.70 mg/kg, and 0.32-16.9 mg/kg, respectively. Concentrations of Cd and As in some samples were higher than national limitation standards. Consumption of 14 common types of seafood would not pose non carcinogenic risk. However, some types, such as sparuslatus, oyster, and porphyra tenera, would form a carcinogenic risk. Regardless of a carcinogenic or non carcinogenic risk, As posed the highest risk on humans. The observed HI value for non-carcinogenic effect of all metals in all seafood reached 0.69-2.20, and the metal orders of risk can be listed as As > Hg > Cr > Cd > Pb, reiterating the risk of As is a matter of concern in seafood from Xiamen markets. PMID- 27194018 TI - Portosystemic Shunt Surgery in Patients with Idiopathic Noncirrhotic Portal Hypertension. AB - BACKGROUND Idiopathic noncirrhotic portal hypertension (INCPH) is a rare disease characterized by increased portal venous pressure in the absence of cirrhosis and other causes of liver diseases. The aim of the present study was to present our results in using portosystemic shunt surgery in patients with INCPH. MATERIAL AND METHODS Patients who had been referred to our Liver Transplantation Institute for liver transplantation and who had undergone surgery from January 2010 to December 2015 were retrospectively analyzed. Patients with INCPH who had undergone portosystemic shunt procedure were included in the study. Age, sex, symptoms and findings, type of portosystemic shunt, and postoperative complications were assessed. RESULTS A total of 1307 patients underwent liver transplantation from January 2010 to December 2015. Eleven patients with INCPH who did not require liver transplantation were successfully operated on with a portosystemic shunt procedure. The mean follow-up was 30.1+/-19 months (range 7-69 months). There was no mortality in the perioperative period or during the follow-up. Two patients underwent surgery again due to intra-abdominal hemorrhage; one had bleeding from the surgical site except the portacaval anastomosis and the other had bleeding from the h-graft anastomosis. No patient developed encephalopathy and no patient presented with esophageal variceal bleeding after portosystemic shunt surgery. Shunt thrombosis occurred in 1 patient (9.9%). Only 1 patient developed ascites, which was controlled medically. CONCLUSIONS Portosystemic shunt surgery is a safe and effective procedure for the treatment of patients with INCPH. PMID- 27194019 TI - Adjuvant gemcitabine monotherapy for resectable perihilar cholangiocarcinoma with lymph node involvement: a propensity score matching analysis. AB - PURPOSE: The aim of this study was to evaluate the efficacy of adjuvant gemcitabine monotherapy following resection for perihilar cholangiocarcinoma with lymph node involvement. METHODS: We performed a retrospective analysis of 180 patients undergoing resection for perihilar cholangiocarcinoma with lymph node involvement between 2001 and 2012. The patients were divided into two groups according to the presence (n = 67) or absence (n = 113) of adjuvant gemcitabine monotherapy. Univariate and multivariate analyses were performed followed by a propensity score matching analysis to adjust for the differences in the baseline characteristics of the groups. RESULTS: The overall survival rates after surgery and the median survival times in patients who were treated with adjuvant chemotherapy were significantly longer than those who were treated without adjuvant chemotherapy (32.9 vs. 15.0 % at 5 years, 37 vs. 20 months, P = 0.001). A multivariate analysis indicated that adjuvant chemotherapy, a residual microscopic tumor, and pathological T stage were independent prognostic factors for survival. After two new cohorts of 32 patients were generated following 1:1 propensity score matching, the overall survival rate in the adjuvant chemotherapy group was found to be significantly longer than that in the surgery alone group (43.2 vs. 15.6 % at 5 years, P = 0.001). CONCLUSION: Adjuvant gemcitabine monotherapy may improve survival in node-positive perihilar cholangiocarcinoma patients. PMID- 27194021 TI - Living the cycle of drinking and violence: A qualitative study of women's experience of alcohol-related intimate partner violence. AB - INTRODUCTION AND AIMS: Heavy and binge drinking contributes to increased risk and severity of violence in intimate relationships, but its role in the initiation and escalation of intimate partner violence (IPV) is not well-understood. This study explores the dynamics of drinking and IPV from the perspectives of women with lived experience of alcohol-related IPV. DESIGN AND METHODS: A qualitative constructivist grounded theory study using interviews with 18 women aged 18-50 years who experienced fear or harm from an alcohol-affected male partner. Participants were recruited from the community in Victoria, Australia. RESULTS: Participants experienced alcohol-related IPV as a cycle of escalating violence accompanying the male partner's progression to intoxication as follows: starting to drink (having fun); getting drunk (looking for a fight); intoxicated ('switching' to escalated violence); drunk (becoming incapacitated); hungover/coming down (becoming mean-tempered); sober (returning to 'normal' life); and craving (building up to drinking again - for dependent drinkers). Participants identified safe and unsafe stages in the cycle but feared the unpredictability of drunken violence. Participants actively managed safety through four main strategies: preventing (e.g. limiting his drinking); predicting (e.g. recognising signs); responding (e.g. avoiding arguments); and protecting (e.g. removing self and children). Anticipating abuse when a partner drinks was the central process for participants living this cycle. DISCUSSION AND CONCLUSIONS: For some women, alcohol plays a central role in the cycle of violence, abuse and fear. Alcohol-related intimate partner violence should be the focus of further research, prevention and treatment. [Wilson IM, Graham K, Taft A. Living the cycle of drinking and violence: A qualitative study of women's experience of alcohol-related intimate partner violence. Drug Alcohol Rev 2017;36:115-124]. PMID- 27194020 TI - Additional surgery for non-curative resection after endoscopic submucosal dissection for gastric cancer: a retrospective analysis of 200 cases. AB - PURPOSE: Endoscopic submucosal dissection is recommended for early gastric cancer with a low risk of lymph node metastasis. When the pathological findings do not meet the curative criteria; then, an additional gastrectomy with lymph node dissection is recommended. However, most cases have neither lymph node metastasis nor a local residual tumor during an additional surgery. METHODS: This was a single-institutional retrospective cohort study, analyzing 200 patients who underwent an additional gastrectomy after non-curative endoscopic submucosal dissection from January 2005 to October 2015. We reviewed the patients' clinicopathological data and evaluated the predictors for the presence of a residual tumor. RESULTS: Histopathology revealed lymph node metastasis in 15 patients (7.5 %) and a local residual tumor in 23 (11.5 %). A multivariable analysis revealed macroscopic findings (flat/elevated type) (p = 0.011, odds ratio = 4.63), lymphatic invasion (p < 0.0001, odds ratio = 14.2), and vascular invasion (p = 0.04, odds ratio = 4.00) to be predictors for lymph node metastasis. A positive vertical margin (p = 0.0027, odds ratio = 3.26) and horizontal margin (p = 0.0008, odds ratio = 5.74) were predictors for a local residual tumor. All cases with lymph node metastasis had lymphovascular invasion with at least one other non-curative factor. CONCLUSIONS: The risk of a residual tumor can, therefore, be estimated based on the histopathology of endoscopic submucosal dissection samples. Lymphovascular invasion appears to be a pivotal predictor of lymph node metastasis. PMID- 27194022 TI - Correlating Emotional Intelligence and Job Performance Among Jordanian Hospitals' Registered Nurses. AB - PROBLEM: Emotional intelligence (EI) is an ability to recognize our and others' emotions, and manage emotions in ourselves and in relationships with other people. A large body of research evidence outside nursing shows that measured (EI) abilities correlated with employee performance, motivation, and job satisfaction; and preliminary nursing research evidence shows the correlation between EI ability and nurses' clinical performance. There is less research on the EI ability of Jordanian nurses, and the present study was undertaken to address this gap. METHODS: A descriptive, cross-sectional, correlation comparative design (nonexperimental) was employed. Six Jordanian hospitals were included in the study. Two hundred fifty questionnaires were distributed to prospective participants. One hundred ninety-four questionnaires were returned, giving a response rate of 78%. EI was measured using the Genos Instrument. Clinical performance was measured using a self-report measure. FINDINGS: Findings demonstrated significant positive relationships between all subscales of EI and job performance, ranging from r = .250, p = .000 to r = .193, p = .007. Regression analysis indicated working in medical-surgical wards, recognizing and expressing emotions scores (beta = 0.186, p = .048), and controlling emotions (beta = 0.255, p = .027) explained 19.1% of variance in nurses' job performance. CONCLUSIONS: The study findings confirm the correlation between nurse EI ability and clinical performance. PMID- 27194023 TI - Clinical outcomes according to QRS duration and morphology in the irbesartan in patients with heart failure and preserved systolic function (I-PRESERVE) trial. AB - BACKGROUND: The aims of this study were to describe the prevalence of QRS prolongation and abnormal QRS morphology in patients with heart failure and preserved ejection fraction (HF-PEF) and to examine the relationship between these QRS abnormalities and clinical outcomes. METHODS AND RESULTS: We categorized patients in the Irbesartan in Heart Failure with Preserved Ejection Fraction trial (I-PRESERVE) according to QRS duration <120 vs. >=120 ms and QRS morphology: normal, left bundle branch block (LBBB), and right bundle branch block (RBBB) or other non-specific intra-ventricular conduction defect (IVCD). The outcomes examined were the composite of cardiovascular death or heart failure hospitalization (and its components) and all-cause mortality. Of the 4128 patients enrolled in I-PRESERVE, 3754 were included in the present analyses. A total of 606 patients had a QRS duration >=120 ms, 302 had LBBB and 742 had RBBB/IVCD. Patients with an abnormal QRS had evidence of more severe heart failure [lower left ventricular ejection fraction, lower estimated glomerular filtration rate, higher N-terminal pro-B-type natriuretic peptide (NT-proBNP)] and worse clinical status (higher New York Heart Association functional class and greater use of diuretics). Both abnormalities of QRS duration and QRS morphology were associated with worse outcomes. The rates of the composite outcome were: 6.0 and 9.3 per 100 patient years in the <120 ms and >=120 ms groups, respectively [adjusted hazard ratio (HR) 1.32, 95% confidence interval (CI) 1.11-1.57; P = 0.002) and 6.0, 7.7 and 8.7 per 100 patient years in the normal, non-LBBB and LBBB groups, respectively (adjusted HR 1.19, 95% CI 1.00-1.42, P = 0.046; and HR 1.31, 95% CI 1.03-1.66, P = 0.026, respectively, compared with normal). The heightened risk related to QRS abnormalities persisted after adjustment for other prognostic variables, including NT-proBNP. CONCLUSION: We found that both prolongation of QRS duration and abnormal QRS morphology were associated with a high risk of fatal and non-fatal adverse outcomes in heart failure with preserved ejection fraction. PMID- 27194024 TI - High-performance Liquid Chromatographic Ultraviolet Detection of Nilotinib in Human Plasma from Patients with Chronic Myelogenous Leukemia, and Comparison with Liquid Chromatography-Tandem Mass Spectrometry. AB - BACKGROUND: A method for determining nilotinib concentration in human plasma is proposed using high-performance liquid chromatography and ultraviolet detection. MATERIALS & METHODS: Nilotinib and the internal standard dasatinib were separated using a mobile phase of 0.5% Na2 PO4 H2 O (pH 2.5)-acetonitrile-methanol (55:25:20, v/v/v) on a Capcell Pak C18 MG II column (250 * 4.6 mm) at a flow rate of 1.0 ml/min, and ultraviolet measurement at 250 nm. RESULTS: The calibration curve exhibited linearity over the nilotinib concentration range of 50-2,500 ng/ml at 250 nm, with relative standard deviations (n = 5) of 7.1%, 2.5%, and 2.9% for 250, 1,500, and 2,500 ng/ml, respectively. The detection limit for nilotinib was 5 ng/ml due to three blank determinations (rho = 3). CONCLUSION: This method was successfully applied to assaying nilotinib in human plasma samples from patients with chronic myelogenous leukemia. In addition, we compared the results with those measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) at BML, Inc. (a commercial laboratory). A strong correlation was observed between the nilotinib concentrations measured by our high-performance liquid chromatographic method and those obtained by LC/MS-MS (r2 = 0.988, P < 0.01). PMID- 27194027 TI - An electromagnetic cell-stretching device for mechanotransduction studies of olfactory ensheathing cells. AB - Olfactory ensheathing cells (OECs) are primary candidates for cell transplantation therapy to repair spinal cord injury (SCI). However, the post transplantation survival of these cells remains a major hurdle for a success using this therapy. Mechanical stimuli may contribute to the maintenance of these cells and thus, mechanotransduction studies of OECs may serve as a key benefit to identify strategies for improvement in cell transplantation. We developed an electromagnetic cell stretching device based on a single sided uniaxial stretching approach to apply tensile strain to OECs in culture. This paper reports the design, simulation and characterisation of the stretching device with preliminary experimental observations of OECs in vitro. The strain field of the deformable membrane was investigated both experimentally and numerically. Heterogeneity of the device provided an ideal platform for establishing strain requirement for the OEC culture. The cell stretching system developed may serve as a tool in exploring the mechanobiology of OECs for future SCI transplantation research. PMID- 27194025 TI - vIL-10-overexpressing human MSCs modulate naive and activated T lymphocytes following induction of collagenase-induced osteoarthritis. AB - BACKGROUND: Recent efforts in osteoarthritis (OA) research have highlighted synovial inflammation and involvement of immune cells in disease onset and progression. We sought to establish the in-vivo immune response in collagenase induced OA and investigate the ability of human mesenchymal stem cells (hMSCs) overexpressing viral interleukin 10 (vIL-10) to modulate immune populations and delay/prevent disease progression. METHODS: Eight-week-old male C57BL/6 mice were injected with 1 U type VII collagenase over two consecutive days. At day 7, 20,000 hMSCs overexpressing vIL-10 were injected into the affected knee. Control groups comprised of vehicle, 20,000 untransduced or adNull-transduced MSCs or virus alone. Six weeks later knees were harvested for histological analysis and popliteal and inguinal lymph nodes for flow cytometric analysis. RESULTS: At this time there was no significant difference in knee OA scores between any of the groups. A trend toward more damage in animals treated with hMSCs was observed. Interestingly there was a significant reduction in the amount of activated CD4 and CD8 T cells in the vIL-10-expressing hMSC group. CONCLUSIONS: vIL-10 overexpressing hMSCs can induce long-term reduction in activated T cells in draining lymph nodes of mice with collagenase-induced OA. This could lead to reduced OA severity or disease progression over the long term. PMID- 27194026 TI - Cloning, Characterization, and Expression Levels of the Nectin Gene from the Tube Feet of the Sea Urchin Paracentrotus Lividus. AB - Marine bioadhesives perform in ways that manmade products simply cannot match, especially in wet environments. Despite their technological potential, bioadhesive molecular mechanisms are still largely understudied, and sea urchin adhesion is no exception. These animals inhabit wave-swept shores, relying on specialized adhesive organs, tube feet, composed by an adhesive disc and a motile stem. The disc encloses a duo-gland adhesive system, producing adhesive and deadhesive secretions for strong reversible substratum attachment. The disclosure of sea urchin Paracentrotus lividus tube foot disc proteome led to the identification of a secreted adhesion protein, Nectin, never before reported in adult adhesive organs but, that given its adhesive function in eggs/embryos, was pointed out as a putative substratum adhesive protein in adults. To further understand Nectin involvement in sea urchin adhesion, Nectin cDNA was amplified for the first time from P. lividus adhesive organs, showing that not only the known Nectin mRNA, called Nectin-1 (GenBank AJ578435), is expressed in the adults tube feet but also a new mRNA sequence, called Nectin-2 (GenBank KT351732), differing in 15 missense nucleotide substitutions. Nectin genomic DNA was also obtained for the first time, indicating that both Nectin-1 and Nectin-2 derive from a single gene. In addition, expression analysis showed that both Nectins are overexpressed in tube feet discs, its expression being significantly higher in tube feet discs from sea urchins just after collection from the field relative to sea urchin from aquarium. These data further advocate for Nectin involvement in sea urchin reversible adhesion, suggesting that its expression might be regulated according to the hydrodynamic conditions. PMID- 27194030 TI - Hamed Khan: Hates classism and prejudice. PMID- 27194028 TI - Perfused drop microfluidic device for brain slice culture-based drug discovery. AB - Living slices of brain tissue are widely used to model brain processes in vitro. In addition to basic neurophysiology studies, brain slices are also extensively used for pharmacology, toxicology, and drug discovery research. In these experiments, high parallelism and throughput are critical. Capability to conduct long-term electrical recording experiments may also be necessary to address disease processes that require protein synthesis and neural circuit rewiring. We developed a novel perfused drop microfluidic device for use with long term cultures of brain slices (organotypic cultures). Slices of hippocampus were placed into wells cut in polydimethylsiloxane (PDMS) film. Fluid level in the wells was hydrostatically controlled such that a drop was formed around each slice. The drops were continuously perfused with culture medium through microchannels. We found that viable organotypic hippocampal slice cultures could be maintained for at least 9 days in vitro. PDMS microfluidic network could be readily integrated with substrate-printed microelectrodes for parallel electrical recordings of multiple perfused organotypic cultures on a single MEA chip. We expect that this highly scalable perfused drop microfluidic device will facilitate high-throughput drug discovery and toxicology. PMID- 27194031 TI - Hypercapnia slows down proliferation and apoptosis of human bone marrow promyeloblasts. AB - Stem cells are being applied in increasingly diverse fields of research and therapy; as such, growing and culturing them in scalable quantities would be a huge advantage for all concerned. Gas mixtures containing 5 % CO2 are a typical concentration for the in vitro culturing of cells. The effect of varying the CO2 concentration on promyeloblast KG-1a cells was investigated in this paper. KG-1a cells are characterized by high expression of CD34 surface antigen, which is an important clinical surface marker for human hematopoietic stem cells (HSCs) transplantation. KG-1a cells were cultured in three CO2 concentrations (1, 5 and 15 %). Cells were batch-cultured and analyzed daily for viability, size, morphology, proliferation, and apoptosis using flow cytometry. No considerable differences were noted in KG-1a cell morphological properties at all three CO2 levels as they retained their myeloblast appearance. Calculated population doubling time increased with an increase in CO2 concentration. Enhanced cell proliferation was seen in cells cultured in hypercapnic conditions, in contrast to significantly decreased proliferation in hypocapnic populations. Flow cytometry analysis revealed that apoptosis was significantly (p = 0.0032) delayed in hypercapnic cultures, in parallel to accelerated apoptosis in hypocapnic ones. These results, which to the best of our knowledge are novel, suggest that elevated levels of CO2 are favored for the enhanced proliferation of bone marrow (BM) progenitor cells such as HSCs. PMID- 27194032 TI - Early weight-bearing and rehabilitation versus immobilisation following surgical Achilles tendon repair (PEDro synthesis). PMID- 27194029 TI - Interstitial Fluid Sphingosine-1-Phosphate in Murine Mammary Gland and Cancer and Human Breast Tissue and Cancer Determined by Novel Methods. AB - The tumor microenvironment is a determining factor for cancer biology and progression. Sphingosine-1-phosphate (S1P), produced by sphingosine kinases (SphKs), is a bioactive lipid mediator that regulates processes important for cancer progression. Despite its critical roles, the levels of S1P in interstitial fluid (IF), an important component of the tumor microenvironment, have never previously been measured due to a lack of efficient methods for collecting and quantifying IF. The purpose of this study is to clarify the levels of S1P in the IF from murine mammary glands and its tumors utilizing our novel methods. We developed an improved centrifugation method to collect IF. Sphingolipids in IF, blood, and tissue samples were measured by mass spectrometry. In mice with a deletion of SphK1, but not SphK2, levels of S1P in IF from the mammary glands were greatly attenuated. Levels of S1P in IF from mammary tumors were reduced when tumor growth was suppressed by oral administration of FTY720/fingolimod. Importantly, sphingosine, dihydro-sphingosine, and S1P levels, but not dihydro S1P, were significantly higher in human breast tumor tissue IF than in the normal breast tissue IF. To our knowledge, this is the first reported S1P IF measurement in murine normal mammary glands and mammary tumors, as well as in human patients with breast cancer. S1P tumor IF measurement illuminates new aspects of the role of S1P in the tumor microenvironment. PMID- 27194033 TI - 'One man's medicine is another man's poison': a qualitative study of user perspectives on low intensity interventions for Obsessive-Compulsive Disorder (OCD). AB - BACKGROUND: Low intensity interventions based on cognitive-behavioral therapy (CBT) such as computerized therapy or guided self-help can offer effective and accessible care for mild to moderate mental health problems. However, critics argue that by reducing therapist input and the level of experience of the professionals delivering therapy, low intensity interventions deprive users of critical 'active ingredients'. Thus, while demand management arguments support the use of low intensity interventions for OCD, their integration into existing mental health services remains incomplete. Studies of user views of low intensity interventions can offer valuable insights to define their role and optimize their implementation in practice. METHODS: Qualitative interviews (n = 36) in adults with OCD explored user perspectives on the initiation, continuation and acceptability of two low intensity CBT interventions: guided self-help (6 h of professional support) and computerized CBT (1 h of professional support), delivered within the context of a large pragmatic effectiveness trial (ISRCTN73535163). RESULTS: While uptake was relatively high, continued engagement with the low intensity interventions was complex, with the perceived limitations of self-help materials impacting on users' willingness to continue therapy. The addition of professional support provided an acceptable compromise between the relative benefits of self-help and the need for professional input. However, individual differences were evident in the extent to which this compromise was considered necessary and acceptable. The need for some professional contact to manage expectations and personalize therapy materials was amplified in users with OCD, given the unique features of the disorder. However, individual differences were again evident regarding the perceived value of face-to-face support. CONCLUSIONS: Overall the findings demonstrate the need for flexibility in the provision of low intensity interventions for OCD, responsive to user preferences, as these preferences impact directly on engagement with therapy and perceptions of effectiveness. PMID- 27194034 TI - The partnership of patient advocacy groups and clinical investigators in the rare diseases clinical research network. AB - BACKGROUND: Among the unique features of the Rare Diseases Clinical Research Network (RDCRN) Program is the requirement for each Consortium to include patient advocacy groups (PAGs) as research partners. This development has transformed the work of the RDCRN and is a model for collaborative research. This article outlines the roles patients and PAGs play in the RDCRN and reports on the PAGs' impact on the Network's success. METHODS: Principal Investigators from the 17 RDCRN Consortia and 28 representatives from 76 PAGs affiliated with these Consortia were contacted by email to provide feedback via an online RDCRN survey. Impact was measured in the key areas of 1) Research logistics; 2) Outreach and communication; and 3) Funding and in-kind support. Rating choices were: 1-very negative, 2-somewhat negative, 3-no impact, 4-somewhat positive, and 5-very positive. RESULTS: Twenty-seven of the PAGs (96 %) disseminate information about the RDCRN within the patient community. The Consortium Principal Investigators also reported high levels of PAG involvement. Sixteen (94 %) Consortium Principal Investigators and 25 PAGs (89 %) reported PAGs participation in protocol review, study design, Consortium conference calls, attending Consortium meetings, or helping with patient recruitment. CONCLUSIONS: PAGs are actively involved in shaping Consortia's research agendas, help ensure the feasibility and success of research protocols by assisting with study design and patient recruitment, and support training programs. This extensive PAG-Investigator partnership in the RDCRN has had a strongly positive impact on the success of the Network. PMID- 27194035 TI - Letter to the Editor: Robotic assisted hysterectomy in obese patients: a systematic review. PMID- 27194036 TI - The dynamics of epidural and opioid analgesia during labour. AB - PURPOSE: To investigate the association of analgesia, opioids or epidural, or the combination of both with labour duration and spontaneous birth in nulliparous women. METHODS: A secondary data analysis of an existing cohort study was performed and included nulliparous women (n = 2074). Durations of total labour and first and second labour stage were calculated with Kaplan-Meier estimation for the four different study groups: no analgesia (n = 620), opioid analgesia (n = 743), epidural analgesia (n = 482), and combined application (n = 229). Labour duration was compared by Cox regression while adjusting for confounders and censoring for operative births. Logistic regression was used to investigate the association between the administration of different types of analgesia and mode of birth. RESULTS: Most women in the combined application group were first to receive opioid analgesia. Women with no analgesia had the shortest duration of labour (log rank p < 0.001) and highest chance of a spontaneous birth (p < 0.001). If analgesia was administered, women with opioids had a shorter first stage (p = 0.018), compared to women with epidural (p < 0.001) or women with combined application (p < 0.001). Women with opioids had an increased chance to reach full cervical dilatation (p = 0.006). Women with epidural analgesia (p < 0.001) and women with combined application (p < 0.001) had a prolonged second stage and decreased chance of spontaneous birth compared to women without analgesia. CONCLUSIONS: Women with opioids had a prolonged first stage, but increased chance to reach full cervical dilatation. Women with epidural analgesia and women with both opioid and epidural analgesia had a prolonged first and second stage and a decreased chance of a spontaneous birth. PMID- 27194037 TI - A Systematic Approach to Assess the Burden of Drug Interactions in Adult Kidney Transplant Patients. AB - AIM: Renal transplant patients are frequently subject to polypharmacy and drug drug interactions. However, no previous study has systematically assessed the risk of drug interactions and Adverse Drug Reactions (ADRs) in this population. METHODS: A total of 138 consecutive adult kidney transplant recipients admitted to our hospital between August 2010 and February 2012 were prospectively and systematically assessed by our pharmacovigilance team, within 24 hours of admission, to identify potential drug-drug interactions and probable ADRs. RESULTS: As a consequence of the high number of medications per patient (7.8+/ 0.2 drugs), a considerable number of drugdrug interactions were observed in this population, with an average of 5.6+/-0.4 drug interactions per patient. Moreover, a significant percentage of admissions (~10%) of kidney transplant patients were related to probable ADRs. Almost all these patients had at least one drug interaction that could have potentially contributed to the probable ADR. Of note, clinically significant (i.e. severe) drug interactions were more frequent among patients with ADRs (29% vs. 15%, p<0.01). Also, patients with ADRs were more likely to have started a medication 30 days before admission (38.5% vs. 10.4%, p < 0.01). Non-immunosuppressive drugs most commonly involved in severe interactions were omeprazole, magnesium sulphate, and statins. The most commonly observed interactions were: tacrolimus and omeprazole, mycophenolate and omeprazole, sirolimus and enalapril, mycophenolate and antivirals, and mycophenolate and magnesium sulphate. CONCLUSION: Drug interactions were extremely frequent among kidney transplant recipients, and responsible for potentially avoidable ADRs. They should be carefully considered when following kidney transplant recipients. PMID- 27194038 TI - In touch with your feminine side: how oestrogen metabolism impacts prostate cancer. AB - Prostate cancer is the primary cancer in males, with increasing global incidence rates making this malignancy a significant healthcare burden. Androgens not only promote normal prostate maturity but also influence the development and progression of prostate cancer. Intriguingly, evidence now suggests endogenous and exogenous oestrogens, in the form of phytoestrogens, may be equally as relevant as androgens in prostate cancer growth. The prostate gland has the molecular mechanisms, catalysed by steroid sulphatase (STS), to unconjugate and utilise circulating oestrogens. Furthermore, prostate tissue also expresses enzymes essential for local oestrogen metabolism, including aromatase (CYP19A1) and 3beta- and 17beta-hydroxysteroid dehydrogenases. Increased expression of these enzymes in malignant prostate tissue compared with normal prostate indicates that oestrogen synthesis is favoured in malignancy and thus may influence tumour progression. In contrast to previous reviews, here we comprehensively explore the epidemiological and scientific evidence on how oestrogens impact prostate cancer, particularly focusing on pre-receptor oestrogen metabolism and subsequent molecular action. We analyse how molecular mechanisms and metabolic pathways involved in androgen and oestrogen synthesis intertwine to alter prostate tissue. Furthermore, we speculate on whether oestrogen receptor status in the prostate affects progression of this malignancy. PMID- 27194039 TI - Thermal Acclimatization in Overwintering Tadpoles of the Green Frog, Lithobates clamitans (Latreille, 1801). AB - Seasonal acclimatization permits organisms to maintain function in the face of environmental change. Tadpoles of the green frog (Lithobates clamitans) overwinter as tadpoles in much of their range. Because they are active in winter, we hypothesized that green frog tadpoles would display acclimatization of metabolic and locomotor function. We collected tadpoles in Sewanee, Tennessee (35.2 degrees N) in winter and summer. Tadpoles collected during each season were tested at both winter (8 degrees C) and summer (26 degrees C) temperatures. Winter tadpoles were able to maintain swimming performance at both temperatures, whereas swimming performance decreased at cold temperatures in summer tadpoles. There was no evidence for seasonal acclimatization of whole-animal metabolic rate. Although whole-animal metabolic acclimatization was not observed, the activities of cytochrome c oxidase, citrate synthase, and lactate dehydrogenase measured in skeletal muscle homogenates showed higher activity in winter acclimatized tadpoles indicating compensation for temperature. Further, the composition of muscle membranes of winter tadpoles had less saturated and more monounsaturated fatty acids and a higher omega-3 balance, unsaturation index, and peroxidation index than summer tadpoles. These data indicate that reversible phenotypic plasticity of thermal physiology occurs in larval green frog tadpoles. They appear to compensate for colder temperatures to maintain burst-swimming velocity and the ability to escape predators without the cost of maintaining a constant, higher standard metabolic rate in the winter. PMID- 27194040 TI - Prediction of all-cause death using (11)C-hydroxyephedrine positron emission tomography in Japanese patients with left ventricular dysfunction. AB - OBJECTIVES: The aim of this study was to determine whether (11)C-hydroxyephedrine ((11)C-HED) can predict adverse events including all-cause death in Japanese patients with left ventricular (LV) dysfunction. BACKGROUND: Although (11)C-HED PET has been used to assess cardiac sympathetic innervation in various disease conditions, data on their prognostic value are limited. METHODS: Sixty patients (mean LVEF, 42 +/- 14 %) with LV dysfunction (42 ischemic and 18 non-ischemic heart disease) underwent (11)C-HED PET. Myocardial retention was calculated for (11)C-HED PET as a measure of cardiac sympathetic neuronal integrity. Statistical analysis was performed using Cox proportional hazards regression and log-rank test. RESULTS: Thirteen deaths (7 cardiac and 6 non-cardiac deaths) occurred during a mean follow-up period of 33 +/- 23 months. The patients with death were associated with significantly lower (11)C-HED retention (7.1 +/- 2.1 vs 9.0 +/- 2.4, p = 0.015) than those without death. The hazard ratio for global (11)C-HED retention per unit (/min) was 0.762 (p = 0.039), which remained significant in multivariate analysis. When the patients were divided into the high (>=8.5) and low (<8.5) (11)C-HED retention groups, the low (11)C-HED retention group was associated with significantly poorer survival than the high (11)C-HED retention group (p = 0.004). CONCLUSION: The low global (11)C-HED retention is a marker of poor overall survival in patients with LV dysfunction in this study. PMID- 27194041 TI - Implication of different clinical and pathological variables in patients with differentiated thyroid cancer on successful ablation for 3700 MBq (131)I: a single Egyptian institutional experience over 14 years. AB - OBJECTIVE: Is to investigate possible factors predicting success of ablation for 3700 MBq radioactive iodine 131 in patients with differentiated thyroid cancer (DTC) following near total thyroidectomy. METHODS: This retrospective study enrolled 272 patients between 2000 and 2014. The success or failure of ablation was assessed 6 months after given the dose and our criteria for complete successful remnant ablation defined as: Negative (131)I whole body scan with no residual functioning thyroid tissue or distant functioning metastases and stimulated thyroglobulin (Tg) level less than 2 ng/ml. Different clinical and pathological factors, such as age, gender, tumor histology, grade and variants, size of primary malignant lesion, stage, and risk assessment according to the American (ATA) and European Thyroid Association (ETA) guidelines, associated pathology, tumor mutifocality, lymph node (LN) metastases and their number, invasiveness of the tumor (capsular invasion of the nodule, extra-thyroidal extension, and vascular invasion), baseline stimulated Tg level, and pre-ablative diagnostic scan were assessed. RESULTS: There were 185 successful ablations (68 %). The baseline-stimulated Tg measured before the ablation was the only independent predictor of ablation success in multivariate analysis (P < 0.0001) with odds ratio (OR) of 2.64 (95 % CI: 1.54-4.54) and the optimal cutoff for this was 3.8 ng/mL. On the univariate analysis, LN metastases was predictor of ablation failure (P value = 0.03). CONCLUSION: Baseline-stimulated Tg level is clinically important and had a significant predictive value for successful ablation; therefore, higher pre-ablation Tg should potentially be incorporated in the decision making for (131)I dosage or other treatment. In accordance with other studies, this is also applicable to cervical lymph nodal involvement and thyroid capsule invasion. PMID- 27194044 TI - Anti-inflammatory use may not negatively impact oncologic outcomes following intravesical BCG for high-grade non-muscle-invasive bladder cancer. AB - PURPOSE: To evaluate whether anti-inflammatory agents affect outcomes in patients receiving intravesical BCG therapy for high-grade (HG) non-muscle-invasive bladder cancer (NMIBC). METHODS: We reviewed the records of 203 patients in a prospective database of HG NMIBC from 2006 to 2012 at a single institution. Patients who had muscle-invasive disease (n = 32), low-grade pathology (n = 4), underwent early cystectomy within 3 months (n = 25), had <3 months of follow-up (n = 11), or did not receive an induction course of intravesical BCG (n = 32) were excluded. Clinicopathologic data were tabulated including demographics, comorbidities, pathologic stage and grades, intravesical therapy, and concomitant use of aspirin, NSAIDs, COX inhibitors, and statins. Multivariate Cox regression analysis explored predictive factors for recurrence, progression (stage progression or progression to cystectomy), cancer-specific survival (CSS), and overall survival (OS). RESULTS: Ninety-nine patients with HG NMIBC who received at least one induction course of intravesical BCG were identified, with median follow-up of 31.4 months. There were 20 (20.2 %) deaths, including 6 (6.1 %) patients with bladder cancer-related mortality. 13 % patients experienced tumor progression and 27 % underwent cystectomy following failure of intravesical therapy. Anti-inflammatory use included statins (65 %), aspirin (63 %), or non aspirin NSAIDs/COX inhibitors (26 %). Anti-inflammatory use was not significantly predictive of recurrence, progression, or mortality outcomes on Cox regression. CIS stage was associated with higher progression, while age, BMI, and Charlson score were independent predictors of overall mortality. CONCLUSION: Despite speculation of inhibitory effects on BCG immunomodulation there was no evidence that anti-inflammatory agents impacted oncologic outcomes in patients receiving BCG for HG NMIBC. PMID- 27194043 TI - Ketamine for Treatment of Suicidal Ideation and Reduction of Risk for Suicidal Behavior. AB - Ketamine, an NMDA receptor antagonist with efficacy as a rapid anti-depressant, has early evidence for action to reduce suicidal ideation. This review will explore several important questions that arise from these studies. First, how do we measure reductions in suicidal ideation that occur over minutes to hours? Second, are the reductions in suicidal ideation after ketamine treatment solely a result of its rapid anti-depressant effect? Third, is ketamine only effective in reducing suicidal ideation in patients with mood disorders? Fourth, could ketamine's action lead us to a greater understanding of the neurobiology of suicidal processes? Last, do the reductions in depression and suicidal ideation after ketamine treatment translate into decreased risk for suicidal behavior? Our review concludes that ketamine treatment can be seen as a double-edged sword, clinically to help provide treatment for acutely suicidal patients and experimentally to explore the neurobiological nature of suicidal ideation and suicidal behavior. PMID- 27194045 TI - Engineering Gene Circuits for Mammalian Cell-Based Applications. AB - Synthetic gene switches are basic building blocks for the construction of complex gene circuits that transform mammalian cells into useful cell-based machines for next-generation biotechnological and biomedical applications. Ligand-responsive gene switches are cellular sensors that are able to process specific signals to generate gene product responses. Their involvement in complex gene circuits results in sophisticated circuit topologies that are reminiscent of electronics and that are capable of providing engineered cells with the ability to memorize events, oscillate protein production, and perform complex information-processing tasks. Microencapsulated mammalian cells that are engineered with closed-loop gene networks can be implanted into mice to sense disease-related input signals and to process this information to produce a custom, fine-tuned therapeutic response that rebalances animal metabolism. Progress in gene circuit design, in combination with recent breakthroughs in genome engineering, may result in tailored engineered mammalian cells with great potential for future cell-based therapies. PMID- 27194048 TI - Setting Single or Multiple Goals for Diet and Physical Activity Behaviors Improves Cardiovascular Disease Risk Factors in Adults With Type 2 Diabetes: A Pragmatic Pilot Randomized Trial. AB - PURPOSE: The purpose of this study was to evaluate a 4-month telephone-based goal setting and decision support intervention among adults with type 2 diabetes mellitus (T2DM) and multiple risk factors for cardiovascular disease (CVD). METHODS: A randomized pretest-posttest control group design was employed. Overweight or obese adults aged 40 to 75 years with T2DM and >=1 additional CVD risk factor were provided with individualized CVD risk information. At baseline and each biweekly telephone call, the multiple-goal group self-selected both diet and physical activity-related goals, the single goal group set a single goal, and the control group received information about community health resources. Dietary intake was assessed via a food frequency questionnaire, physical activity via questionnaire, and A1C and blood lipids via fasting fingerstick sample. Between-group differences for clinical (ie, A1C, blood pressure, and blood lipids), physical activity, and dietary variables were evaluated using Kruskal Wallis, Mann-Whitney U, analysis of variance, and t tests. RESULTS: From pre- to postintervention, the single-goal group demonstrated significant improvement in systolic blood pressure and intake of servings of fruits, vegetables, and refined grains (all P < .05). The multiple-goal group reported significant reduction in percent energy from total, saturated, monounsaturated, and trans fat intake and significant increase in leisure time walking (all P < .05). CONCLUSION: A multiple-goal approach over 4 months can improve dietary and physical activity outcomes, while a single-goal approach may facilitate improvement in one behavioral domain. Additional research is needed to evaluate maintenance of the achieved changes. PMID- 27194051 TI - Behavioral responses to injury and death in wild Barbary macaques (Macaca sylvanus). AB - The wounding or death of a conspecific has been shown to elicit varied behavioral responses throughout thanatology. Recently, a number of reports have presented contentious evidence of epimeletic behavior towards the dying and dead among non human animals, a behavioral trait previously considered uniquely human. Here, we report on the behavioral responses of Barbary macaques, a social, non-human primate, to the deaths of four group members (one high-ranking adult female, one high-ranking adult male, one juvenile male, and one female infant), all caused by road traffic accidents. Responses appeared to vary based on the nature of the death (protracted or instant) and the age class of the deceased. Responses included several behaviors with potential adaptive explanations or consequences. These included exploration, caretaking (guarding, carrying, and grooming), and proximity to wounded individuals or corpses, and immediate as well as longer lasting distress behaviors from other group members following death, all of which have been reported in other non-human primate species. These observations add to a growing body of comparative evolutionary analysis of primate thanatology and help to highlight the multifaceted impacts of human-induced fatalities on an endangered and socially complex primate. PMID- 27194049 TI - A new endovascular strategy utilizing a hybrid procedure for long segmental occlusion by acute arterial thromboembolism in the lower extremity. AB - PURPOSE: To evaluate a new endovascular strategy utilizing a hybrid procedure for long segmental arterial thromboembolism in a lower extremity by historical comparison with conventional endovascular strategy. MATERIALS AND METHODS: In a new endovascular strategy, a hybrid procedure was performed for long segmental thromboembolism (longer than 15 cm) and an endovascular procedure for short segmental thromboembolism. The new strategy group (Group A) consisted of 24 procedures (13 hybrid procedures, 11 endovascular procedures) in 19 patients. Data were retrospectively collected from 24 consecutive procedures in 23 patients treated with the conventional strategy (Group B). RESULT: The technical success of Groups A and B was 24/24 and 20/24, respectively (p = 0.11). Major amputation or mortality was not observed in Group A, whereas 3 major amputations and 4 deaths occurred in Group B. Clinical failure in Groups A and B was 0/24 and 7/24, respectively (p < 0.05). Continuous urokinase (UK) infusion was needed in 1/24 in Group A and 14/24 in Group B (p < 0.05). Mean procedure time was 4 h 17 min for Group A and 21 h 30 min for Group B (p < 0.05). CONCLUSION: The hybrid procedure may be faster and more effective than the conventional treatment in long segmental arterial thromboembolisms, while the conventional treatment is still effective for short segmental occlusions. PMID- 27194050 TI - Host specialization of the blast fungus Magnaporthe oryzae is associated with dynamic gain and loss of genes linked to transposable elements. AB - BACKGROUND: Magnaporthe oryzae (anamorph Pyricularia oryzae) is the causal agent of blast disease of Poaceae crops and their wild relatives. To understand the genetic mechanisms that drive host specialization of M. oryzae, we carried out whole genome resequencing of four M. oryzae isolates from rice (Oryza sativa), one from foxtail millet (Setaria italica), three from wild foxtail millet S. viridis, and one isolate each from finger millet (Eleusine coracana), wheat (Triticum aestivum) and oat (Avena sativa), in addition to an isolate of a sister species M. grisea, that infects the wild grass Digitaria sanguinalis. RESULTS: Whole genome sequence comparison confirmed that M. oryzae Oryza and Setaria isolates form a monophyletic and close to another monophyletic group consisting of isolates from Triticum and Avena. This supports previous phylogenetic analysis based on a small number of genes and molecular markers. When comparing the host specific subgroups, 1.2-3.5 % of genes showed presence/absence polymorphisms and 0-6.5 % showed an excess of non-synonymous substitutions. Most of these genes encoded proteins whose functional domains are present in multiple copies in each genome. Therefore, the deleterious effects of these mutations could potentially be compensated by functional redundancy. Unlike the accumulation of nonsynonymous nucleotide substitutions, gene loss appeared to be independent of divergence time. Interestingly, the loss and gain of genes in pathogens from the Oryza and Setaria infecting lineages occurred more frequently when compared to those infecting Triticum and Avena even though the genetic distance between Oryza and Setaria lineages was smaller than that between Triticum and Avena lineages. In addition, genes showing gain/loss and nucleotide polymorphisms are linked to transposable elements highlighting the relationship between genome position and gene evolution in this pathogen species. CONCLUSION: Our comparative genomics analyses of host-specific M. oryzae isolates revealed gain and loss of genes as a major evolutionary mechanism driving specialization to Oryza and Setaria. Transposable elements appear to facilitate gene evolution possibly by enhancing chromosomal rearrangements and other forms of genetic variation. PMID- 27194047 TI - Network-assisted investigation of virulence and antibiotic-resistance systems in Pseudomonas aeruginosa. AB - Pseudomonas aeruginosa is a Gram-negative bacterium of clinical significance. Although the genome of PAO1, a prototype strain of P. aeruginosa, has been extensively studied, approximately one-third of the functional genome remains unknown. With the emergence of antibiotic-resistant strains of P. aeruginosa, there is an urgent need to develop novel antibiotic and anti-virulence strategies, which may be facilitated by an approach that explores P. aeruginosa gene function in systems-level models. Here, we present a genome-wide functional network of P. aeruginosa genes, PseudomonasNet, which covers 98% of the coding genome, and a companion web server to generate functional hypotheses using various network-search algorithms. We demonstrate that PseudomonasNet-assisted predictions can effectively identify novel genes involved in virulence and antibiotic resistance. Moreover, an antibiotic-resistance network based on PseudomonasNet reveals that P. aeruginosa has common modular genetic organisations that confer increased or decreased resistance to diverse antibiotics, which accounts for the pervasiveness of cross-resistance across multiple drugs. The same network also suggests that P. aeruginosa has developed mechanism of trade-off in resistance across drugs by altering genetic interactions. Taken together, these results clearly demonstrate the usefulness of a genome-scale functional network to investigate pathogenic systems in P. aeruginosa. PMID- 27194053 TI - Primary Clear Cell Carcinoma of the Non-cirrhotic Liver Presenting as an Acute Abdomen: a Case Report and Review of the Literature. PMID- 27194046 TI - Epigenetic Determinants of Cancer. AB - SUMMARYEpigenetic changes are present in all human cancers and are now known to cooperate with genetic alterations to drive the cancer phenotype. These changes involve DNA methylation, histone modifiers and readers, chromatin remodelers, microRNAs, and other components of chromatin. Cancer genetics and epigenetics are inextricably linked in generating the malignant phenotype; epigenetic changes can cause mutations in genes, and, conversely, mutations are frequently observed in genes that modify the epigenome. Epigenetic therapies, in which the goal is to reverse these changes, are now one standard of care for a preleukemic disorder and form of lymphoma. The application of epigenetic therapies in the treatment of solid tumors is also emerging as a viable therapeutic route. PMID- 27194052 TI - Effect of hyaluronic acid on morphological changes to dentin surfaces and subsequent effect on periodontal ligament cell survival, attachment, and spreading. AB - OBJECTIVES: Hyaluronic acid (HA) is a natural constituent of connective tissues and plays an important role in their development, maintenance, and regeneration. Recently, HA has been shown to improve wound healing. However, no basic in vitro study to date has investigated its mode of action. Therefore, the purpose of this study was to examine morphological changes of dentin surfaces following HA coating and thereafter investigate the influence of periodontal ligament (PDL) cell survival, attachment, and spreading to dentin discs. MATERIALS AND METHODS: HA was coated onto dentin discs utilizing either non-cross-linked (HA) or cross linked (HA cl) delivery systems. Morphological changes to dentin discs were then assessed using scanning electron microscopy (SEM). Thereafter, human PDL cells were seeded under three in vitro conditions including (1) dilution of HA (1:100), (2) dilution of HA (1:10), and (3) HA coated directly to dentin discs. Samples were then investigated for PDL cell survival, attachment, and spreading using a live/dead assay, cell adhesion assay, and SEM imaging, respectively. RESULTS: While control dentin discs demonstrated smooth surfaces both at low and high magnification, the coating of HA altered surface texture of dentin discs by increasing surface roughness. HA cl further revealed greater surface texture/roughness likely due to the cross-linking carrier system. Thereafter, PDL cells were seeded on control and HA coated dentin discs and demonstrated a near 100 % survival rate for all samples demonstrating high biocompatibility of HA at dilutions of both 1:100 and 1:10. Interestingly, non-cross-linked HA significantly increased cell numbers at 8 h, whereas cross-linked HA improved cell spreading as qualitatively assessed by SEM. CONCLUSIONS: The results from the present study demonstrate that both carrier systems for HA were extremely biocompatible and demonstrated either improved cell numbers or cell spreading onto dentin discs. Future in vitro and animal research is necessary to further characterize the optimal delivery system of HA for improved clinical use. CLINICAL RELEVANCE: HA is a highly biocompatible material that may improve PDL cell attachment or spreading on dentin. PMID- 27194054 TI - Determining predictive factors for immune checkpoint inhibitor toxicity: Response to Letter to the Editors "A case report of insulin-dependent diabetes as immune related toxicity of pembrolizumab: presentation, management and outcome". PMID- 27194056 TI - Niche Overlap and Network Specialization of Flower-Visiting Bees in an Agricultural System. AB - Different resource use strategies manifest as differences in the realized niches of species. Niche segregation may involve several dimensions of the niche, such as diet, space, and time. We measured the level of redundancy and complementarity of a bee-plant interaction network in an agricultural system. Because flower resource diversity is high and resource abundance associated with flowering phenology varies throughout the year, we hypothesized that trophic overlap in the community would be low (i.e., high niche complementarity). In contrast, we expected a combination of physiological constraints and exploitation competition to create high temporal overlap, leading to high redundancy in the time of use of floral resources. Dietary overlap was low (NOih = 0.18): niches of 88% of species pairs had less than 30% overlap. In contrast, temporal overlap was intermediate (NOih = 0.49): niches of 65% of species pairs had 30% to 60% overlap. Network analysis showed that bees separated their dietary niches and had intermediate complementary specialization (H2' = 0.46). In terms of their temporal niches (H2' = 0.12), bees were generalists, with high temporal redundancy. Temperature was not a key factor in the determination of niche overlap, suggesting that environmental factors do not likely have a primary role in determining high redundancy in the temporal use of floral resources. Rather, temporal overlap is likely associated with the timing of nectar production by flowers. Our results suggest that bees partition a wide variety of available floral resources, resulting in low dietary overlap and intermediate temporal overlap. PMID- 27194057 TI - Reproductive Status of Females in the Eusocial Wasp Polistes ferreri Saussure (Hymenoptera: Vespidae). AB - In the subfamily Polistinae, caste dimorphism is not pronounced and differences among females are primarily physiological and behavioral. We investigated factors that indicate the reproductive status in females of Polistes ferreri Saussure. We analyzed females from nine colonies and evaluated morphometric parameters, ovarian development, occurrence of insemination, relative age, and cuticular chemical profile. The colony females showed three kinds of ovarian development: type A, filamentous ovarioles; type B, ovarioles containing partially developed oocytes; and type C, long and well-developed ovarioles containing two or more mature oocytes. The stepwise discriminant analysis of the cuticular chemical profile showed that it was possible to distinguish the three groups of females: workers 1, workers 2, and queens. However, the stepwise discriminant analysis of the morphological differences did not show significant differences among these groups. The queens were among the older females in the colony and were always inseminated, while the age of the workers varied according to the stage of colony development. PMID- 27194055 TI - Abnormal Epigenetic Modifications in Peripheral T Cells from Patients with Abdominal Aortic Aneurysm Are Correlated with Disease Development. AB - BACKGROUND: Increasing evidence suggests that abdominal aortic aneurysm (AAA) is a T-cell-mediated autoimmune condition. This study investigates the epigenetic modifications that occur in the T cells of AAA patients and evaluates the correlation of these modifications with disease development. METHODS AND RESULTS: Peripheral T cells were collected from 101 AAA patients and 102 healthy controls (HCs). DNA methylation and histone acetylation levels were measured by ELISA. Methyl-CpG-binding domain, DNA methyltransferase (DNMT) and histone deacetylase (HDAC) mRNA levels were determined by real-time PCR. DNA from the T cells of the AAA patients exhibited significant hypomethylation compared with the HCs (1.6 fold, p < 0.0001). Expression of DNMT1 at the mRNA level in the T cells of the AAA patients was 1.52-fold lower than that of the HCs (p < 0.0001). The extent of DNA methylation in the AAA patients was negatively correlated with the corresponding aortic diameter (r = -0.498, p < 0.0001). H3 (1.59-fold, p < 0.0001) and H3K14 (2.15-fold, p < 0.0001) acetylation levels in the T cells of the AAA patients were higher than those of the HCs, but the HDAC1 mRNA level was 2.33-fold lower than that of the HCs (p < 0.0001). CONCLUSIONS: DNA methylation and the histone modification status are significantly altered in the T cells of AAA patients. These changes could play a pivotal role in the activation of pathological immune responses and may influence AAA development. PMID- 27194058 TI - No Evidence of Habitat Loss Affecting the Orchid Bees Eulaema nigrita Lepeletier and Eufriesea auriceps Friese (Apidae: Euglossini) in the Brazilian Cerrado Savanna. AB - Habitat loss, landscape fragmentation, and agriculture intensification constitute the main threats to bees. As the organisms responsible for almost one third of the food produced worldwide, there are growing concerns on bees' response to human-related disturbances. Among all bee groups, orchid bees (Apidae: Euglossini) compose an interesting group to test landscape-related hypotheses. In here, we tested the effect of landscape features (amount of anthropic areas and isolation) on the probability of occurrence and the abundances of both Eulaema nigrita Lepeletier and Eufriesea auriceps Friese in the Cerrado savanna. In general, we did not observe any effect of landscape features on the probability of occurrence and abundances of both species in our sampling sites. Given their potential high dispersal abilities, these bee species may be less sensitive to fragmented landscapes or even positively affected by the increase of anthropic habitats. Since we sampled many E. nigrita specimens in highly preserved Cerrado savanna areas, we believe that at least for this biome, this species may not be a good indicator of landscape disturbance. PMID- 27194059 TI - Differential Recruitment of Camponotus femoratus (Fabricius) Ants in Response to Ant Garden Herbivory. AB - Although several studies have shown that ants can recognize chemical cues from their host plants in ant-plant systems, it is poorly demonstrated in ant gardens (AGs). In this interaction, ant species constantly interact with various epiphyte species. Therefore, it is possible to expect a convergence of chemical signals released by plants that could be acting to ensure that ants are able to recognize and defend epiphyte species frequently associated with AGs. In this study, it was hypothesized that ants recognize and differentiate among chemical stimuli released by AG epiphytes and non-AG epiphytes. We experimentally simulated leaf herbivore damage on three epiphyte species restricted to AGs and a locally abundant understory herb, Piper hispidum, in order to quantify the number of recruited Camponotus femoratus (Fabricius) defenders. When exposed to the AG epiphytes Peperomia macrostachya and Codonanthe uleana leaves, it was observed that the recruitment of C. femoratus workers was, on average, respectively 556% and 246% higher than control. However, the number of ants recruited by the AG epiphyte Markea longiflora or by the non-AG plant did not differ from paper pieces. This indicated that ants could discern between chemicals released by different plants, suggesting that ants can select better plants. These results can be explained by evolutionary process acting on both ants' capability in discerning plants' chemical compounds (innate attraction) or by ants' learning based on the epiphyte frequency in AGs (individual experience). To disentangle an innate behavior, a product of classical coevolutionary process, from an ant's learned behavior, is a complicated but important subject to understand in the evolution of ant-plant mutualisms. PMID- 27194060 TI - Toward the Identification of the Sex Pheromone of Diatraea indigenella Dyar & Heinrich (Lepidoptera: Crambidae): Calling Behavior and Chemical Structure of a Major Component. AB - Behavioral patterns and pheromone titer in females of the steam borer Diatraea indigenella Dyar & Heinrich were assessed for 7 days during scotophase under a 13:11 L:D photoperiod. Calling was observed from the first scotophase for most of the females. The highest percentage of calling females was recorded 6 h after the onset of scotophase. Calling bouts and length of calling were affected by age, decreasing dramatically after the sixth scotophase. By coupling chemical and electrophysiological techniques (GC-EAD, GC-MS) and olfactometer bioassays (Z,E) 9,11-hexadecadienal was identified as the main sex pheromonal component in the extracts of female glands. The concentration varied from 2.53 to 13.7 ng gland( 1) with a peak at the 6th hour of scotophase. In addition, two unidentified secondary active components were detected at very low concentrations. Behavioral assays showed that 86% of the male moths were more attracted to the gland extracts than to hexane (control), and 77% of the male moths were more attracted to the gland extract than to the synthetic major component (Z,E)-9,11 hexadecadienal. However, 68% of males preferred the synthetic major component over hexane. The identification of the major sex pheromonal component represents an important step toward the complete elucidation of the composition of the sex pheromone of D. indigenella in order to develop monitoring tools. PMID- 27194061 TI - Taxonomic and Functional Structure of Phytophagous Insect Communities Associated with Grain Amaranth. AB - Amaranthus are worldwide attacked mainly by leaf chewers and sucker insects. Stem borers and leaf miners follow in importance, while minor herbivores are leaf rollers, folders, and rasping-sucking insects. The herbivorous community observed on Amaranthus spp. in Argentina was consistent with the information reported worldwide both in guild composition and order proportion. Amaranth plants had a higher number of phytophagous species in their native rather than in its introduced range. Occurrence of insect guilds differed in space and time. The highest density of leaf chewers was observed shortly after the emergence of plants, while higher density of borer and sucker insects coincided with reproductive stages of the crop. The sucking guild was observed mainly at panicles, while the insects within the leaf chewer group were registered in both leaves (92.6%, n = 746 adults) and inflorescences (7.4%). The borer guild was also recorded in stems and inflorescences; however, the density of larvae in stems was about four times as high as the density observed in panicles (n = 137 larvae). PMID- 27194062 TI - Two New Species of the Genus Formosatettixoides Zheng (Orthoptera: Tetrigidae). AB - Taxonomy of a tetrigid genus Formosatettixoides Zheng is reviewed. Two new species, Formosatettixoides nigellus n. sp. and Formosatettixoides dabieshanensis n. sp. are described. Redescription of the characters of the genus is given, the distribution and an updated key to the now 10 species of the genus are presented. PMID- 27194063 TI - Description of a New Species of the Genus Macromotettixoides Zheng (Orthoptera: Tetrigoidea: Metrodorinae) from China. AB - A new species, Macromotettixoides lativertex Deng et al n. sp. is described with detailed illustrations of external morphology. Comparison between the species M. lativertex n. sp. and allied species is compiled into a table for identification. The distribution and an updated identification key to all known species of the genus is given. PMID- 27194064 TI - Four New Ladybug Species Belonging to Decadiomus Chapin (Coleoptera: Coccinellidae) from Puerto Rico. AB - While searching for native natural enemies attacking invasive insect pests in Puerto Rico, we found four undescribed ladybug species belonging to the Caribbean ladybug genus Decadiomus Chapin. In this article, we describe the following species from Puerto Rico: Decadiomus seini n. sp., Decadiomus ramosi n. sp., Decadiomus hayuyai n. sp., and Decadiomus martorelli n. sp. Illustrations of the dorsal habitus, shape of prosternal carinae, and drawings of male and female genitalia are presented. We also present a key for Diomini of Puerto Rico and discuss their importance as potential biocontrol agents. PMID- 27194065 TI - Effects of Five Naturally Occurring Sugars on the Longevity, Oogenesis, and Nutrient Accumulation Pattern in Adult Females of the Synovigenic Parasitoid Neochrysocharis formosa (Hymenoptera: Eulophidae). AB - Neochrysocharis formosa (Westwood) (Hymenoptera: Eulophidae), one of the dominant natural enemies of agromyzid leafminers, is a synovigenic parasitoid. We compared the longevity, oogenesis, and nutrient levels of female wasps provided with 10% solutions of five naturally occurring sugars. All five sugars significantly increased the longevity of female wasps, which was 6.5-9.3-fold higher than that of parasitoids provided with water only. We found no significant difference in longevity of female wasps fed on glucose versus fructose or trehalose versus melezitose, but longevity of wasps fed on glucose or fructose was significantly longer than those fed on trehalose or melezitose. Also, we examined the oosorption capability of wasps fed on the five sugars. Some mature eggs were present in the ovaries of newly emerged females, but these were fully reabsorbed within 72 h when wasps were starved. Once wasps were fed with any of the sugars, the number of mature eggs increased at first and then decreased due to oosorption. The longevity and oogenesis dynamics of female wasps fed on five sugars were related with their function of hydrolysis and digestion. As female wasps have no lipogenesis capability, by acquiring exogenous sugars for oogenesis, they can either maintain or exceed the original level of capital nutrients held on adult emergence because none of the wasps' glycogen need be metabolized to burn as sugar. PMID- 27194067 TI - Antibiosis in Soybean Genotypes and the Resistance Levels to Spodoptera eridania (Cramer) (Lepidoptera: Noctuidae). AB - The southern armyworm (SAW) Spodoptera eridania (Cramer) is one of the most common armyworm species defoliating soybeans. Preliminary screening trials have indicated that some soybean genotypes exhibit resistance to SAW. Therefore, in this study, we evaluated the development of SAW larvae fed on ten soybean genotypes in order to identify genotypes with antibiosis-type resistance. Neonate SAW larvae were daily fed with young leaves collected from plants at the vegetative growth stages V4-V5. Larval development and survival were recorded. Genotypes PI 227687 and PI 227682 delayed larval, pupal, and larva-adult development and yielded larvae with the lowest weight and survival and pupae with the lowest weight. Genotypes IAC 100 and DM 339 also negatively affected larval and pupal development and larval survival but at a lower level. Based on our results, the soybean lines PI 227687 and PI 227682 could be used as sources of genes for soybean breeding programs aiming to develop high yield, SAW-resistant cultivars. Moreover, further trials must be carried out under field conditions to validate if the commercial cultivars IAC 100 and DM 339, which expressed moderate levels of antibiosis-type resistance in the laboratory, are effective in suppressing SAW larvae populations. PMID- 27194066 TI - Performance of Bemisia tabaci (Genn.) Biotype B (Hemiptera: Aleyrodidae) on Weeds. AB - Bemisia tabaci (Genn.) biotype B (Hemiptera: Aleyrodidae) is regarded as a pest with a large number of hosts, including crops and weeds. The performance of this whitefly on seven weeds was evaluated in order to identify the most suitable host. The following weeds that are very common in intense agricultural areas in the state of Sao Paulo, Brazil, were selected for this study: spurge (Euphorbia heterophylla), beggarticks (Bidens pilosa), red tasselflower (Emilia sonchifolia), small-flower galinsoga (Galinsoga parviflora), pigweed (Amaranthus viridis), black nightshade (Solanum americanum), and morning glory (Ipomoea sp.). In free-choice tests, adult preference and oviposition were greatest on spurge. In contrast, morning glory was the least attractive and least oviposited plant. In assays carried out for egg-adult development, egg viability was greater than 87% over all weeds, whereas nymph viability ranged from 74 to 97%. The developmental period from egg to adult ranged from 26.7 to 49.1 days among the hosts under study. The lowest nymph density rate was observed for beggarticks and morning glory. Cluster analysis resulted in a single group formed by spurge, indicating its superiority as a host for B. tabaci biotype B. Even though the parameters evaluated indicate that spurge is the most suitable host among the weeds, all the others allow the reproduction of B. tabaci biotype B. For this reason, they should be observed during cropping and the intercrop period in areas infested by this whitefly. PMID- 27194069 TI - Potential Effects of Nonsteroidal Anti-Inflammatory Drugs in the Prevention and Treatment of Type 2 Diabetes Mellitus. AB - Nonsteroidal anti-inflammatory drugs (NSAIDs) are a group of heterogeneous drugs largely known for their anti-inflammatory, antipyretic, and analgesic effects, which are met by means of the inhibition of the cyclooxygenase (COX) enzymes. Even when their use in patients with diabetes mellitus is limited due to relevant adverse events, some pharmacological and metabolic effects of NSAIDs have been further studied to be potentially beneficial in the prevention and/or treatment of diabetic subjects. Effects on endogenous glucose production, peripheral insulin resistance, pancreatic islet, and systemic inflammation and the insulin clearance have been reported. In this article, we overview the scientific literature of the last 5 years regarding the potential effects of NSAID treatment on diabetes prevention/treatment. The selected papers showed information in both humans and animal models. Furthermore, we included papers that suggest new areas for further investigation, and we discussed our own suggestions on this matter. PMID- 27194070 TI - New Novel Treatment Approaches for Heart Failure With Reduced Ejection Fraction. AB - Despite availability of standardized drug therapies with proven beneficial outcomes, heart failure is associated with poor quality of life, increased hospital readmission, and high mortality rate. In the recent years, comprehensive understanding of the pathophysiological mechanisms of heart failure has led to the development and approval of 2 new pharmacological agents, sacubitril valsartan and ivabradine. These agents are currently approved for use in heart failure with reduced ejection fraction (HFrEF) and present as novel approaches to further improve prognosis and outcomes in patients with HF. They offer alternative treatment options for patients who are intolerant or continue to be symptomatic despite utilization of standard HF drug therapies at optimally tolerated dosages. A review of these 2 novel agents in HFrEF, including information on pivotal trials that led to its approval and its place in therapy for HFrEF, is presented. PMID- 27194071 TI - Preparing Students to Enter the Race for Postgraduate Training. AB - PURPOSE: Exposure of pharmacy students to postgraduate training prior to clinical practice is currently endorsed by national professional organizations. To meet this goal, colleges and schools of pharmacy are developing residency preparation programs. In this descriptive report, we review published studies of curricular activities and structured programs from academic institutions across the United States aimed at preparing students for residency training and promoting postgraduate education. Additionally, we discuss our experience developing a residency preparation program at Touro College of Pharmacy (TCOP). SUMMARY: A literature search yielded 15 residency preparation programs. While the format, content, and length of programs varied, there were common components such as curriculum vitae critique, mock interviews, and focused sessions on the residency application process. At TCOP, a 5-themed residency preparation workshop series was implemented during the third and fourth academic year. The workshops were modeled after existing programs and included several of the core components. One feature unique to the TCOP program was the addition of multiple mock interviews. CONCLUSION: The growing focus on residency training has led to increased competition among applicants. To better prepare students for this rigorous application and interview process, development of structured residency preparation programs, similar to TCOP's, should be encouraged. PMID- 27194068 TI - Mucosal adherent bacterial dysbiosis in patients with colorectal adenomas. AB - Recent reports have suggested that the gut microbiota is involved in the progression of colorectal cancer (CRC). The composition of gut microbiota in CRC precursors has not been adequately described. To characterize the structure of adherent microbiota in this disease, we conducted pyrosequencing-based analysis of 16S rRNA genes to determine the bacterial profile of normal colons (healthy controls) and colorectal adenomas (CRC precursors). Adenoma mucosal biopsy samples and adjacent normal colonic mucosa from 31 patients with adenomas and 20 healthy volunteers were profiled using the Illumina MiSeq platform. Principal coordinate analysis (PCoA) showed structural segregation between colorectal adenomatous tissue and control tissue. Alpha diversity estimations revealed higher microbiota diversity in samples from patients with adenomas. Taxonomic analysis illustrated that abundance of eight phyla (Firmicutes, Proteobacteria, Bacteroidetes, Actinobacteria, Chloroflexi, Cyanobacteria, Candidate-division TM7, and Tenericutes) was significantly different. In addition, Lactococcus and Pseudomonas were enriched in preneoplastic tissue, whereas Enterococcus, Bacillus, and Solibacillus were reduced. However, both PCoA and cluster tree analyses showed similar microbiota structure between adenomatous and adjacent non adenoma tissues. These present findings provide preliminary experimental evidence supporting that colorectal preneoplastic lesion may be the most important factor leading to alterations in bacterial community composition. PMID- 27194072 TI - The origin of novel features by changes in developmental mechanisms: ontogeny and three-dimensional microanatomy of polyodontode scales of two early osteichthyans. AB - Recent advances in synchrotron imaging allow us to study the three-dimensional (3D) histology of vertebrate fossils, including microfossils (e.g. teeth and scales) of early jawed vertebrates. These microfossils can often be scanned at submicron resolution (<1 um) because of their small size. The resulting voxel (3D pixel) stacks can be processed into virtual thin sections revealing almost every internal detail of the samples, comparable to traditional thin sections. In addition, 3D models of the internal microanatomical structures, such as embedded odontodes and vasculature, can be assembled and examined in situ. Scales of two early osteichthyans, Psarolepis romeri from the Early Devonian of China and Andreolepis hedei from the Late Silurian of Sweden, were scanned using propagation phase-contrast synchrotron X-ray microtomography (PPC-SRuCT), and 3D models of internal canal systems and buried odontodes were created from the scans. Based on these new data, we review the evolutionary origin of cosmine and its associated pore-canal system, which has been long recognized as a synapomorphy of sarcopterygians. The first odontode that appeared during growth shows almost identical morphology in the two scales, but the second odontode of the Psarolepis scale shows a distinctive morphology with several pores on the surface. It is suggested that a shift from ridge-like odontode to pore-bearing odontode was the key step in the origin of cosmine, which was then elaborated further in more-derived sarcopterygians. We perform a detailed comparison between the two scales and propose a primary homology framework to generate microanatomical characters, which can be used in the phylogenetic analysis of early osteichthyans when more 3D data become available. Our results highlight the importance of 3D data for the study of histology and ontogeny of the dermal skeleton of early jawed vertebrates, especially scales of the polyodontode type. The traditional microvertebrate collection is not only useful for biostratigraphic studies, but also preserves invaluable biological information about the growth of vertebrate hard tissues. Today, we are only beginning to understand the biological meaning of the new 3D data. The increasing availability of such data will enable, and indeed require, a complete revision of traditional palaeohistological studies on early vertebrates. PMID- 27194074 TI - New approaches to infection prevention and control: implementing a risk-based model regionally. AB - QUALITY ISSUE: Infectious disease outbreaks result in substantial inconvenience to patients and disruption of clinical activity. INITIAL ASSESSMENT: Between 1 April 2008 and 31 March 2009, the Vancouver Island Health Authority (Island Health) declared 16 outbreaks of Vancomycin Resistant Enterococci and Clostridium difficile in acute care facilities. As a result, infection prevention and control became one of Island Health's highest priorities. CHOICE OF SOLUTION: Quality improvement methodology, which promotes a culture of co-production between front line staff, physicians and Infection Control Practitioners, was used to develop and test a bundle of changes in practices. IMPLEMENTATION: A series of rapid Plan Do-Study-Act cycles, specific to decreasing hospital-acquired infections, were undertaken by a community hospital, selected for its size, clinical specialty representation, and enthusiasm amongst staff and physicians for innovation and change. Positive results were incorporated into practice at the test site, and then introduced throughout the rest of the Health Authority. EVALUATION: The changes implemented as a result of this study have enabled better control of antibiotic resistant organisms and have minimized disruption to routine activity, as well as saving an estimated $6.5 million per annum. When outbreaks do occur, they are now controlled much more promptly, even in existing older facilities. LESSONS LEARNED: Through this process, we have changed our approach in Infection Prevention and Control (IPAC) from a rules-based approach to one that is risk based, focusing attention on identifying and managing high-risk situations. PMID- 27194073 TI - Clinical Trials in Neurovirology: Successes, Challenges, and Pitfalls. AB - Clinical trials in neurovirology illustrate the special challenges confronting investigators planning to study these conditions, as well as the contributions of successful trials in establishing appropriate management for these devastating diseases. This article reviews key examples of progress in neurovirology that have been spurred by clinical trials, emphasizing human herpes virus encephalitis, HIV, and JC virus. Clinical trials in the setting of neurovirological diseases are characterized by specific challenges, which may include small sample sizes, clinical presentations from life-threatening conditions to chronic courses of disease, regional and temporally restricted outbreaks scenarios, and the unavailability of validated diagnostic tests that can be rapidly deployed at the bedside. This review aims to highlight these methodological challenges and pitfalls in designing and executing clinical neurovirology trials, as well as to outline innovative trial designs, which could be useful in addressing common challenges. PMID- 27194075 TI - The efficacy of nerve growth factor antibody in a mouse model of neuropathic cancer pain. AB - Neuropathic cancer pain is caused by tumors compressing the spinal nerve roots and is usually difficult to treat. The aim of current study was to determine the influence of NGF antibody on pain-related markers and behavior in a mouse model of neuropathic cancer pain. Twenty mice were used to model neuropathic cancer pain by applying murine sarcoma cells to their left sciatic nerve. Ten mice were sham operated. Two weeks after surgery, the murine sarcoma-affected mice were allocated randomly into treatment groups receiving either sterile saline (saline group) or an anti-nerve growth factor antibody (anti-NGF group). Three weeks after surgery (a week after treatment), the pain-related behavior of mice was evaluated using a CatWalk system. Subsequently, bilateral dorsal root ganglia (DRGs) from the L4-L6 levels and spinal cords at L4-L6 levels were resected. DRGs were immunostained for calcitonin gene-related peptide (CGRP) and activating transcription factor 3 (ATF-3), and spinal cords were immunostained for ionized calcium-binding adaptor molecule-1 (iba-1). Mechanical allodynia was observed in mice from the saline group and was improved in mice from the anti-NGF group. CGRP and ATF-3-immunoreactivity in DRGs and microglia expression in the spinal dorsal horn were upregulated in the saline group compared with the sham group, and they were suppressed in the anti-NGF group compared with the saline group (P<0.05). These findings suggest that anti-NGF therapy might be valuable for treating neuropathic cancer pain. PMID- 27194076 TI - Probabilistic measures of cost-effectiveness. AB - Several probability-based measures are introduced in order to assess the cost effectiveness of a treatment. The basic measure consists of the probability that one treatment is less costly and more effective compared with another. Several variants of this measure are suggested as flexible options for cost-effectiveness analysis. The proposed measures are invariant under monotone transformations of the cost and effectiveness measures. Interval estimation of the proposed measures are investigated under a parametric model, assuming bivariate normality, and also non-parametrically. The delta method and a generalized pivotal quantity approach are both investigated under the bivariate normal model. A non-parametric U statistics-based approach is also investigated for computing confidence intervals. Numerical results show that under bivariate normality, the solution based on generalized pivotal quantities exhibits accurate performance in terms of maintaining the coverage probability of the confidence interval. The non parametric U-statistics-based solution is accurate for sample sizes that are at least moderately large. The results are illustrated using data from a clinical trial for prostate cancer therapy. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27194078 TI - Long-distance temporal quantum ghost imaging over optical fibers. AB - Since the first quantum ghost imaging (QGI) experiment in 1995, many QGI schemes have been put forward. However, the position-position or momentum-momentum correlation required in these QGI schemes cannot be distributed over optical fibers, which limits their large-scale geographical applications. In this paper, we propose and demonstrate a scheme for long-distance QGI utilizing frequency correlated photon pairs. In this scheme, the frequency correlation is transformed to the correlation between the illuminating position of one photon and the arrival time of the other photon, by which QGI can be realized in the time domain. Since frequency correlation can be preserved when the photon pairs are distributed over optical fibers, this scheme provides a way to realize long distance QGI over large geographical scale. In the experiment, long-distance QGI over 50 km optical fibers has been demonstrated. PMID- 27194077 TI - Volume perfusion CT imaging of cerebral vasospasm: diagnostic performance of different perfusion maps. AB - INTRODUCTION: In this study, we aimed to evaluate the diagnostic performance of different volume perfusion CT (VPCT) maps regarding the detection of cerebral vasospasm compared to angiographic findings. METHODS: Forty-one datasets of 26 patients (57.5 +/- 10.8 years, 18 F) with subarachnoid hemorrhage and suspected cerebral vasospasm, who underwent VPCT and angiography within 6 h, were included. Two neuroradiologists independently evaluated the presence and severity of vasospasm on perfusion maps on a 3-point Likert scale (0-no vasospasm, 1 vasospasm affecting <50 %, 2-vasospasm affecting >50 % of vascular territory). A third neuroradiologist independently assessed angiography for the presence and severity of vasospasm on a 3-point Likert scale (0-no vasospasm, 1-vasospasm affecting < 50 %, 2-vasospasm affecting > 50 % of vessel diameter). Perfusion maps of cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and time to drain (TTD) were evaluated regarding diagnostic accuracy for cerebral vasospasm with angiography as reference standard. Correlation analysis of vasospasm severity on perfusion maps and angiographic images was performed. Furthermore, inter-reader agreement was assessed regarding findings on perfusion maps. RESULTS: Diagnostic accuracy for TTD and MTT was significantly higher than for all other perfusion maps (TTD, AUC = 0.832; MTT, AUC = 0.791; p < 0.001). TTD revealed higher sensitivity than MTT (p = 0.007). The severity of vasospasm on TTD maps showed significantly higher correlation levels with angiography than all other perfusion maps (p <= 0.048). Inter-reader agreement was (almost) perfect for all perfusion maps (kappa >= 0.927). CONCLUSION: The results of this study indicate that TTD maps have the highest sensitivity for the detection of cerebral vasospasm and highest correlation with angiography regarding the severity of vasospasm. PMID- 27194080 TI - Chiral Ferrocenyl P,N-Ligands for Palladium-Catalyzed Asymmetric Formal [3 + 2] Cycloaddition of Propargylic Esters with beta-Ketoesters: Access to Functionalized Chiral 2,3-Dihydrofurans. AB - A highly enantioselective palladium-catalyzed [3 + 2] cycloaddition of propargylic esters with beta-ketoesters has been realized by employing a newly developed chiral ferrocene/benzimidazole-based P,N-ligand. This protocol features a good tolerance of functional groups in both propargylic esters and beta ketoesters, thereby delivering a variety of highly functionalized chiral 2,3 dihydrofurans bearing an exocyclic double bond at the 3-position in good yields and with high enantioselectivities (up to 98% ee). PMID- 27194079 TI - Alterations in antioxidant and oxidant status of children after on-pump surgery for cyanotic and acyanotic congenital heart diseases. AB - OBJECTIVE: Oxidative stress refers to an imbalance between reactive oxidative species and antioxidants. In this case-controlled, prospective, observational study, we investigated the total oxidant status, total antioxidant status, oxidative stress index, and albumin and C-reactive protein levels of children with cyanotic and acyanotic congenital heart diseases who had undergone on-pump cardiac surgery. METHOD: The study groups consisted of 60 patients with congenital heart disease, who were operated under cardiopulmonary bypass, and a control group of 30 healthy individuals. The patients were classified into two groups. Among them, one was a patient group that consisted of 30 patients with acyanotic congenital heart disease and the other group consisted of 30 patients with cyanotic congenital heart disease. In the patient groups, blood samples were collected before surgery and at one and 24 hours following surgery. In control groups, blood samples were collected once during hospital admission. RESULTS: No statistically significant differences were found between the groups in terms of baseline total oxidant status, total antioxidant status, and oxidative stress index values. Regarding the postoperative first-hour and 24-hour total oxidant status and total antioxidant status levels as well as oxidative stress index values, there were no significant differences between the groups, except for an increase in total antioxidant status levels (p=0.002) 24 hours after surgery in cyanotic patients. CONCLUSION: There was no difference between oxidative stress status of cyanotic and acyanotic congenital heart disease patients and healthy individuals. Oxidative stress status of cyanotic and acyanotic patients does not change after cardiac surgery under cardiopulmonary bypass. PMID- 27194085 TI - Detection of UVA/UVC-induced damage of p53 fragment by rolling circle amplification with AIEgens. AB - Absorption of ultraviolet (UV) light by nucleic acid could lead to mutations and skin cancers. Traditional damage detection methods based on fluorescence not only need dye/quencher groups but also display relatively high background interference, causing difficulty in synthesis and purification and thus low specificity of detection. Here, by combining rolling circle amplification (RCA) and aggregation-induced emission molecules (AIE), we made up for the defects of traditional methods to some extent and could also differentiate damaged and undamaged DNA. We also studied radiation damage of the p53 gene fragment both from UVA and UVC, although the mechanism of UVA in mutagenesis remains controversial. To amplify the signal-to-background ratio, we ligated the linear p53 (L p53) gene fragment to be a circular p53 (C p53) gene fragment, which is a key component for RCA. The combination of RCA products and positive TPE-Z (quaternized tetraphenylethene salt) molecules induced the aggregation of AIE molecules, and subsequently resulted in significant fluorescence enhancement (the signal for the undamaged DNA is 598% higher than that of the damaged). Compared with the traditional aggregation-caused quenching (ACQ) based fluorescent method, our assay was more sensitive and more specific. PMID- 27194086 TI - Heart failure: Finerenone vs eplerenone for patients with HFrEF. PMID- 27194088 TI - Arrhythmias: Arrhythmia risk stratification using virtual heart models. PMID- 27194087 TI - Surgery: Don't STICS to statins in cardiac surgery. PMID- 27194089 TI - Genetics: Non-HDL cholesterol confers increased risk of CAD. PMID- 27194090 TI - Arrhythmias: Ablation of ventricular tachycardia in ischaemic cardiomyopathy. PMID- 27194092 TI - Coronary artery disease: Ceramides predict CV death in stable CAD and ACS. PMID- 27194094 TI - Can a continuous mineral foam explain the stiffening of aged bone tissue? A micromechanical approach to mineral fusion in musculoskeletal tissues. AB - Recent experimental data revealed a stiffening of aged cortical bone tissue, which could not be explained by common multiscale elastic material models. We explain this data by incorporating the role of mineral fusion via a new hierarchical modeling approach exploiting the asymptotic (periodic) homogenization (AH) technique for three-dimensional linear elastic composites. We quantify for the first time the stiffening that is obtained by considering a fused mineral structure in a softer matrix in comparison with a composite having non-fused cubic mineral inclusions. We integrate the AH approach in the Eshelby based hierarchical mineralized turkey leg tendon model (Tiburtius et al 2014 Biomech. MODEL: Mechanobiol. 13 1003-23), which can be considered as a base for musculoskeletal mineralized tissue modeling. We model the finest scale compartments, i.e. the extrafibrillar space and the mineralized collagen fibril, by replacing the self-consistent scheme with our AH approach. This way, we perform a parametric analysis at increasing mineral volume fraction, by varying the amount of mineral that is fusing in the axial and transverse tissue directions in both compartments. Our effective stiffness results are in good agreement with those reported for aged human radius and support the argument that the axial stiffening in aged bone tissue is caused by the formation of a continuous mineral foam. Moreover, the proposed theoretical and computational approach supports the design of biomimetic materials which require an overall composite stiffening without increasing the amount of the reinforcing material. PMID- 27194093 TI - A description of sleep behaviour in healthy late pregnancy, and the accuracy of self-reports. AB - BACKGROUND: The importance of maternal sleep and its contribution to maternal and fetal health during pregnancy is increasingly being recognised. However, the ability to accurately recall sleep practices during pregnancy has been questioned. The aim of this study is to test the accuracy of recall of normal sleep practices in late pregnancy. METHODS: Thirty healthy women between 35 and 38 weeks of gestation underwent level III respiratory polysomnography (PSG) with infrared digital video recordings in their own homes. Data regarding sleep positions, number of times getting out of bed during the night and respiratory measures were collected. A sleep questionnaire was administered the morning after the recorded sleep. Continuous data were assessed using Spearman's Rho and Bland Altman. Cohen's Kappa was used to assess recall in the categorical variables. RESULTS: Two-thirds of participants went to sleep on their left side. There was good agreement in sleep onset position between video and questionnaire data (Kappa 0.52), however the there was poor agreement on position on wakening (Kappa 0.24). The number of times getting out of bed during the night was accurately recalled (Kappa 0.65). Twenty five out of 30 participants snored as recorded by PSG. Questionnaire data was inaccurate for this measure. Bland-Altman plots demonstrated acceptable agreement between video and questionnaire data for estimated sleep duration, but not the time taken to fall asleep (sleep latency). One participant had mild obstructive sleep apnoea and another probable high upper airways resistance. CONCLUSIONS: Sleep onset position, sleep duration and the number of times getting out of bed during the night were accurately recalled, but sleep latency and sleep position on waking were not. This study identifies the sleep variables that can be accurately obtained by questionnaire and those that cannot. PMID- 27194096 TI - UTILIZATION OF MATERNAL HEALTH SERVICES AMONG INTERNAL MIGRANTS IN MUMBAI, INDIA. AB - This study aimed to understand access to maternal health care and the factors shaping it amongst poor migrants in Mumbai, India. A cross-sectional mixed methods approach was used. It included multistage cluster sampling and face-to face interviews, through structured interview schedules, of 234 migrant women who had delivered in the two years previous to the date they were interviewed. Qualitative in-depth interviews of migrant women, health care providers and health officials were also conducted to understand community and provider perspectives. The results showed that access to antenatal care was poor among migrants with less than a third of them receiving basic antenatal care and a quarter delivering at home. Multivariate analysis highlighted that amongst migrant women those who stayed in Mumbai during pregnancy and delivery had better access to maternal health care than those who went back to their home towns. Poor maternal health care was also due to weaker demand for health care as a result of the lack of felt-need among migrants due to socio-cultural factors and lack of social support for, and knowledge of, health facilities in the city. Supply-side factors such as inadequate health infrastructure at primary and secondary levels, lack of specific strategies to improve access to health care for migrants and cumbersome administrative procedures that exclude migrants from certain government programmes all need to be addressed. Migrants should be integral to the urban development process and policies should aim at preventing their exclusion from basic amenities and their entitlements as citizens. PMID- 27194095 TI - Effects of biotic and abiotic factors on phenotypic partitioning of wing morphology and development in Sclerodermus pupariae (Hymenoptera: Bethylidae). AB - Wing phenotype polymorphism is commonly observed in insects, yet little is known about the influence of environmental cues on the development or expression of the alternative phenotypes. Here, we report how both biotic and abiotic factors affect the wing morph differentiation of a bethylid parasitoid Sclerodermus pupariae. The percentage of winged female parasitoid progeny increased exponentially with temperature between 20 degrees C to 30 degrees C. Low intensity light and short-day photoperiod conditions also significantly induced the development of winged morphs. Interestingly, wingless maternal parasitoids produced more winged progeny. Furthermore, the degree of wing dimorphism was significantly influenced by the interactions between light intensity and maternal wing morphs. The percentage of winged female progeny was not significantly influenced by foundress densities, but increased significantly with parasitoid brood sizes. However, the percentage of male progeny increased significantly with the densities of maternal parasitoids. Our findings highlight the phenotypic partitioning of wing morphology and development in the parasitoid S. pupariae under varied environmental cues, and reveal the most favourable conditions for the production of winged females in this bethylid wasp. It is thus possible to increase winged female parasitoid production for the purposes of biological control by manipulation of biotic and abiotic conditions. PMID- 27194097 TI - Role of clinical pharmacist in the management of blood pressure in dialysis patients. AB - Background Hypertension is highly prevalent yet undertreated condition in hemodialysis patients. Objective The objective of this study was to evaluate clinical pharmacist's role in the management of blood pressure in hemodialysis patients guided by home blood pressure monitoring. Setting Outpatient hemodialysis units of Jordan University Hospital and Isra'a Hospital. Method This was a randomized controlled study. It lasted 6 months (September 2011 till the end of March 2012). All hypertensive patients receiving hemodialysis were invited to participate in the study. Out of 60 patients approached, 56 were actually included. Patients were randomly allocated to an intervention (29) or control group (27). In the intervention arm, patients received physician-pharmacist collaborative care. While in the control arm patients received standard medical care. Main outcome measure Percentage of patients achieving weekly average home blood pressure below or equal 135/85 mmHg. Other secondary measures that were assessed include absolute reduction in peridialysis blood pressure, interdialytic weight gain, adherence to medications and dialysis sessions. Results A total of 52 patients completed the study. Forty-six percent of patients in the intervention arm achieved BP target (mean home blood pressure <=135/85 mmHg) compared to only 14.3 % of patients in the control arm (p = 0.02). Average decline in weekly mean home systolic blood pressure was 10.9 +/- 17.7 mmHg in the intervention arm (p = 0.004), while weekly mean home systolic blood pressure increased by 3.5 +/- 18.4 mmHg in the control arm (p = 0.396). No significant reduction was achieved in weekly home diastolic blood pressure, dialysis blood pressure readings, or interdialytic weight gain in either arm. Conclusions Clinical pharmacist-physicians' collaboration improved rate of blood pressure control in hemodialysis patients. Using home blood pressure monitoring was found to be an efficient way to guide blood pressure therapy. PMID- 27194099 TI - Confinement and viscosity ratio effect on droplet break-up in a concentrated emulsion flowing through a narrow constriction. AB - This paper describes the dimensionless groups that determine the break-up probability of droplets in a concentrated emulsion during its flow in a tapered microchannel consisting of a narrow constriction. Such channel geometry is commonly used in droplet microfluidics to investigate the content of droplets from a concentrated emulsion. In contrast to solid wells in multi-well plates, drops are metastable, and are prone to break-up which compromises the accuracy and the throughput of the assay. Unlike single drops, the break-up process in a concentrated emulsion is stochastic. Analysis of the behavior of a large number of drops (N > 5000) shows that the probability of break-up increases with applied flow rate, the size of the drops relative to the size of the constriction, and the viscosity ratio of the emulsion. This paper shows that the break-up probability collapses into a single curve when plotted as a function of the product of capillary number, viscosity ratio, and confinement factor defined as the un-deformed radius of the drop relative to the hydraulic radius of the constriction. Fundamentally, the results represent a critical step towards the understanding of the physics governing instability in concentrated emulsions. Practically, the results provide a direct guide for the rational design of microchannels and the choice of operation parameters to increase the throughput of the droplet interrogation step while preserving droplet integrity and assay accuracy. PMID- 27194098 TI - Stakeholders' views on granting prescribing authority to pharmacists in Nigeria: a qualitative study. AB - Background In Nigeria, only medical doctors, dentists and some nurses in primary care facilities have the legal right to prescribe medicines to patients. Patients' access to prescription medicines can be seriously affected by the shortage of prescribers leading to longer waiting times in hospitals. Objective This research was carried out to investigate stakeholders' views on granting prescribing authority to pharmacists in Nigeria. Setting The study was conducted in Nigeria. Methods Qualitative, semi-structured interviews were conducted with 43 Nigerian stakeholders including policymakers, pharmacists, doctors and patient group representatives. Transcribed interviews were entered into the QSR NVivo 10 software and analysed using a thematic approach. Main outcome measure Stakeholders' perception on the granting of prescribing authority to pharmacists in Nigeria. Results Three major themes emerged from the interviews: (1) prescribing as a logical role for pharmacists, (2) pharmacist prescribing- an opportunity or a threat and (3) the potential barriers to pharmacist prescribing. Many non-medical stakeholders including pharmacists and patient group representatives supported an extended role for pharmacists in prescribing while the majority of medical doctors including those in policy making were reluctant to do so. Generally, all stakeholders perceived that pharmacist prescribing represents an opportunity to increase patients' access to medicines, reduce doctors' workload and promote the utilisation of pharmacists' skills. However, many stakeholders including pharmacists and doctors commonly identified pharmacists' inadequate skills in diagnosis, medical resistance and shortage of pharmacists as potential barriers to the introduction of pharmacist prescribing in Nigeria. Conclusion The present study showed a split of opinion between participants who were medical doctors and those who were non-doctors in their support for pharmacist prescribing. However, all stakeholders acknowledged the potential of pharmacist prescribing to increase patients' access to medicines in Nigeria. PMID- 27194091 TI - Vein graft failure: from pathophysiology to clinical outcomes. AB - Occlusive arterial disease is a leading cause of morbidity and mortality worldwide. Aside from balloon angioplasty, bypass graft surgery is the most commonly performed revascularization technique for occlusive arterial disease. Coronary artery bypass graft surgery is performed in patients with left main coronary artery disease and three-vessel coronary disease, whereas peripheral artery bypass graft surgery is used to treat patients with late-stage peripheral artery occlusive disease. The great saphenous veins are commonly used conduits for surgical revascularization; however, they are associated with a high failure rate. Therefore, preservation of vein graft patency is essential for long-term surgical success. With the exception of 'no-touch' techniques and lipid-lowering and antiplatelet (aspirin) therapy, no intervention has hitherto unequivocally proven to be clinically effective in preventing vein graft failure. In this Review, we describe both preclinical and clinical studies evaluating the pathophysiology underlying vein graft failure, and the latest therapeutic options to improve patency for both coronary and peripheral grafts. PMID- 27194100 TI - Integrative functional genomic delineation of the cascades of transcriptional changes involved in hepatocellular carcinoma progression. AB - Development of targeted therapeutics is still at its early stage for hepatocellular carcinoma (HCC) due to the incomplete understanding of the confounding regulations at signaling pathway level. In this investigation, gene co-expression-based networking and integrative functional genomic modeling of HCC mRNA profiles as signaling processes were employed to understand the complex signaling cascades involved in HCC development toward understanding the avenues for targeted therapeutics. Multiple sets of genes and molecular biological processes involved during HCC development were identified from this integrative analysis: (i) Loss of liver cellular features due to the reduced HNF4A & PPAR signaling in the early stages of HCC, (ii) activated inflammatory and stress signals in the cirrhosis stages and (iii) highly activated cellular proliferation with the activated E2F-MYC oncogenic signaling with the gain of embryonic liver stem cell-like features in the advanced stage tumors. Upon connecting these gene sets with the established drug sensitivity-related gene signatures, targeted therapeutic strategies for the heterogeneous HCC conditions have been identified. PPAR agonist class of drugs for early stage HCC conditions, anti-inflammatory drugs for cirrhosis and topoisomerase inhibitors for the advanced HCC conditions were inferred. Integrative functional genomic analysis of HCC transcriptome profiles at the context of signaling pathways has defined the key molecular processes involved in HCC development. Further, the study highlights the stage specific and pathway focused targeted therapeutics for HCC. These findings deserve extensive preclinical explorations toward the establishment of targeted therapeutics. PMID- 27194102 TI - Serotonin-induced contractile responses of esophageal smooth muscle in the house musk shrew (Suncus murinus). AB - BACKGROUND: Serotonin (5-hydroxytryptamine, 5-HT) is a regulatory factor in motility of the gastrointestinal tract including the esophagus. Although we proposed that vagal cholinergic and mast cell-derived non-cholinergic components including serotonin coordinately shorten the esophagus, the precise mechanism of serotonin-induced contractions in the suncus esophagus is still unclear. Therefore, the aims of this study were to determine characteristics of contractile responses induced by serotonin and to identify 5-HT receptor subtypes responsible for regulating motility in the suncus esophagus. METHODS: An isolated segment of the suncus esophagus was placed in an organ bath, and longitudinal or circular mechanical responses were recorded using a force transducer. KEY RESULTS: Serotonin evoked contractile responses of the suncus esophagus in the longitudinal direction but not in the circular direction. Tetrodotoxin did not affect the serotonin-induced contractions. Pretreatment with a non-selective 5-HT receptor antagonist or double application of 5-HT1 and 5-HT2 receptor antagonists blocked the serotonin-induced contractions. 5-HT1 and 5-HT2 receptor agonists, but not a 5-HT3 receptor agonist, evoked contractile responses in the suncus esophagus. CONCLUSION & INFERENCES: The findings suggest that serotonin induces contractile responses of the longitudinal smooth muscle in the muscularis mucosae of the suncus esophagus that are mediated via 5-HT1 and 5-HT2 receptors on muscle cells. The serotonin-induced contractions might contribute to esophageal peristalsis and emetic response. PMID- 27194101 TI - ISPD produces CDP-ribitol used by FKTN and FKRP to transfer ribitol phosphate onto alpha-dystroglycan. AB - Mutations in genes required for the glycosylation of alpha-dystroglycan lead to muscle and brain diseases known as dystroglycanopathies. However, the precise structure and biogenesis of the assembled glycan are not completely understood. Here we report that three enzymes mutated in dystroglycanopathies can collaborate to attach ribitol phosphate onto alpha-dystroglycan. Specifically, we demonstrate that isoprenoid synthase domain-containing protein (ISPD) synthesizes CDP ribitol, present in muscle, and that both recombinant fukutin (FKTN) and fukutin related protein (FKRP) can transfer a ribitol phosphate group from CDP-ribitol to alpha-dystroglycan. We also show that ISPD and FKTN are essential for the incorporation of ribitol into alpha-dystroglycan in HEK293 cells. Glycosylation of alpha-dystroglycan in fibroblasts from patients with hypomorphic ISPD mutations is reduced. We observe that in some cases glycosylation can be partially restored by addition of ribitol to the culture medium, suggesting that dietary supplementation with ribitol should be evaluated as a therapy for patients with ISPD mutations. PMID- 27194103 TI - Strigolactones are required for nitric oxide to induce root elongation in response to nitrogen and phosphate deficiencies in rice. AB - The response of the root system architecture to nutrient deficiencies is critical for sustainable agriculture. Nitric oxide (NO) is considered a key regulator of root growth, although the mechanisms remain unknown. Phenotypic, cellular and genetic analyses were undertaken in rice to explore the role of NO in regulating root growth and strigolactone (SL) signalling under nitrogen-deficient and phosphate-deficient conditions (LN and LP). LN-induced and LP-induced seminal root elongation paralleled NO production in root tips. NO played an important role in a shared pathway of LN-induced and LP-induced root elongation via increased meristem activity. Interestingly, no responses of root elongation were observed in SL d mutants compared with wild-type plants, although similar NO accumulation was induced by sodium nitroprusside (SNP) application. Application of abamine (the SL inhibitor) reduced seminal root length and pCYCB1;1::GUS expression induced by SNP application in wild type; furthermore, comparison with wild type showed lower SL-signalling genes in nia2 mutants under control and LN treatments and similar under SNP application. Western blot analysis revealed that NO, similar to SL, triggered proteasome-mediated degradation of D53 protein levels. Therefore, we presented a novel signalling pathway in which NO-activated seminal root elongation under LN and LP conditions, with the involvement of SLs. PMID- 27194104 TI - Glucose-sensitive polymer nanoparticles for self-regulated drug delivery. AB - Glucose-sensitive drug delivery systems, which can continuously and automatically regulate drug release based on the concentration of glucose, have attracted much interest in recent years. Self-regulated drug delivery platforms have potential application in diabetes treatment to reduce the intervention and improve the quality of life for patients. At present, there are three types of glucose sensitive drug delivery systems based on glucose oxidase (GOD), concanavalin A (Con A), and phenylboronic acid (PBA) respectively. This review covers the recent advances in GOD-, Con A-, or PBA-mediated glucose-sensitive nanoscale drug delivery systems, and provides their major challenges and opportunities. PMID- 27194105 TI - Large-Scale and Defect-Free Silicon Metamaterials with Magnetic Response. AB - All-dielectric metamaterials offer a potential low-loss alternative to plasmonic metamaterials at optical frequencies. Here, we experimentally demonstrate a silicon based large-scale magnetic metamaterial, which is fabricated with standard photolithography and conventional reactive ion etching process. The periodically arrayed silicon sub-wavelength structures possess electric and magnetic responses with low loss in mid-infrared wavelength range. We investigate the electric and magnetic resonances dependencies on the structural parameters and demonstrate the possibility of obtaining strong dielectric-based magnetic resonance through a broad band range. The optical responses are quite uniform over a large area about 2 * 2 cm(2). The scalability of this design and compatibility fabrication method with highly developed semiconductor devices process could lead to new avenues of manipulating light for low-loss, large-area and real integrated photonic applications. PMID- 27194106 TI - Will an algal CO2-concentrating mechanism work in higher plants? AB - Many algae use a biophysical carbon concentrating mechanism for active accumulation and retention of inorganic carbon within chloroplasts, with CO2 fixation by RuBisCO within a micro-compartment, the pyrenoid. Engineering such mechanisms into higher plant chloroplasts is a possible route to augment RuBisCO operating efficiency and photosynthetic rates. Significant progress has been made recently in characterising key algal transporters and identifying factors responsible for the aggregation of RuBisCO into the pyrenoid. Several transporters have now also been successfully incorporated into higher plant chloroplasts. Consistent with the predictions from modelling, regulation of higher plant plastidic carbonic anhydrases and some form of RuBisCO aggregation will be needed before the mechanism delivers potential benefits. Key research priorities include a better understanding of the regulation of the algal carbon concentrating mechanism, advancing the fundamental characterisation of known components, evaluating whether higher plant chloroplasts can accommodate a pyrenoid, and, ultimately, testing transgenic lines under realistic growth conditions. PMID- 27194107 TI - Cementless anatomical prosthesis for the treatment of 3-part and 4-part proximal humerus fractures: cadaver study and prospective clinical study with minimum 2 years followup. AB - INTRODUCTION: The purpose of this study was to evaluate the functional and radiological outcomes of a cementless, trauma-specific locked stem for 3- and 4 part proximal humeral fractures. MATERIALS AND METHODS: This study consisted of two parts: a cadaver study with 22 shoulders and a multicenter prospective clinical study of 23 fracture patients evaluated at least 2 years after treatment. In the cadaver study, the locked stem (Humelock(TM), FX Solutions) and its instrumentation were evaluated. In the clinical study, five senior surgeons at four different hospitals performed the surgical procedures. An independent surgeon evaluated the patients using clinical (Constant score, QuickDASH) and radiological (X-rays, CT scans) outcome measures. RESULTS: The cadaver study allowed us to validate the height landmarks relative to the pectoralis major tendon. In the clinical study, at the review, abduction was 95 degrees (60-160), forward flexion was 108 degrees (70-160), external rotation (elbow at body) was 34 degrees (0-55), the QuickDASH was 31 (4.5-59), the overall Constant score was 54 (27-75), and the weighted Constant score was 76 (31.5-109). DISCUSSION: This preliminary study of hemiarthroplasty (HA) with a locked stem found results that were at least equivalent to published series. As all patients had at least a 2 year follow-up, integration of the locked stem did not cause any specific complications. These results suggest that it is possible to avoid using cement when hemiarthroplasty is performed for the humeral stem. This implant makes height adjustment and transosseous suturing of the tuberosities more reproducible. PMID- 27194108 TI - Femoral shaft fracture osteosynthesis in a critically ill patient under Extracorporeal Membrane Oxygenation (ECMO). AB - INTRODUCTION: Extracorporeal Membrane Oxygenation (ECMO) is an invasive procedure used in critically ill patients with catastrophic pulmonary failure or cardiogenic shock in which conventional management has failed. These patients are managed with permanent anticoagulation, with increased bleeding risk. Hemorrhage is the main reported complication. CASE: A 25-year-old polytraumatized woman, both lower limbs amputated and a left femoral shaft fracture with catastrophic pulmonary failure (Murray score 4) that required intensive management care with ECMO. During her evolution definitive femoral shaft osteosynthesis with a nail as required and the medical team decided to operate on the patient under ECMO. She recovered with fluctuations in her hematocrit, but was hemodynamically stable. The patient recovered satisfactorily, was weaned from ECMO and commenced her rehabilitation program. At 16 months, she was almost autovalent, and full consolidation was achieved, with no complication of the implants. DISCUSSION: ECMO is a life-saving support, but requires permanent anticoagulation, which implies a high risk of hemorrhages, specially for surgical treatment. This patient underwent an osteosynthesis surgery satisfactorily. Hematoma was the only complication of her intramedullary femoral nail, without compromising hemodynamics. This case shows that patients on ECMO can undergo a major orthopedic surgery in selected cases. PMID- 27194109 TI - Biomechanical properties of osteoporotic rat femurs after different hormonal treatments: genistein, estradiol, and estradiol/progesterone. AB - INTRODUCTION: The purpose of the study is to compare the effects of genistein, estradiol, estradiol/progesterone combination on the bone mineral density and biomechanical properties of ovariectomized rats' bone. METHODS: 50 female adult Sprague-Dawley rats were divided into five groups. Bilaterally ovaeriectomy were performed in all groups except the sham-operated group. Groups were a sham operated group and a control group (water was given), estradiol treated group (17 beta estradiol 0.015 mg/kg per day), genistein treated group (genistein 10 mg/kg per day), and an estradiol/progesterone combination group (17-beta estradiol 0.015 mg/kg plus drosperinone 0.028 mg/kg per day). The water or hormones were implemented in relevant groups for eight weeks by orogasthric catheter. The bone mineral density and biomechanical properties of the femur were analyzed. RESULTS: Genistein, estradiol, and estradiol/progesterone groups increased bone mineral density significantly compared to the control group. In diaphysis and metaphysis bending test, all groups had higher peak load values than the control group. There were statistically significant differences between the estrogen/progesterone group and control group in diaphysis bending with regard to peak load. There were statistically significant differences between the estradiol and control groups in metaphysis bending with regard to peak load. In axial rotation test, all groups had higher peak torque values than the control groups. CONCLUSIONS: Genistein, estradiol and estrogen/progesterone combination improved the biomechanical properties of the ovariectomized rat bone. Genistein which has less side effects may be considered as an alternative in the treatment of postmenopausal osteoporosis. PMID- 27194110 TI - Gorham-Stout syndrome of the shoulder. AB - INTRODUCTION: Gorham-Stout syndrome (GSS) is a rare but severe subtype of idiopathic osteolysis. There are no guidelines for the treatment of GSS. We analysed different diagnostic and therapeutic regimes and we describe the sucessful treatment of GSS considering individual patient factors. METHODS: We diagnosed three patients with shoulder-specific GSS using clinical, radiological and histopathological examinations. Two out of three patients with similar clinical appearances were treated non-operatively. One patient was treated by reverse shoulder arthroplasty. All patients were analysed retrospectively using clinical and radiological evaluation with a mean follow-up of 42 (range 30-50) months. RESULTS: Two patients had few symptoms of GSS and were treated conservatively. One patient underwent arthroplasty, with a good clinical result. No additional therapy, such as radiation or anti-resorptive medications, was needed for the stable fixation of the prosthesis and the termination of osteolysis. In all patients we found good clinical outcomes with high patient satisfaction. DISCUSSION: GSS is diagnosed after exclusion of infectious, malignant, and systemic disorders. The diagnosis should be supported by clinical, radiological, and histopathological characteristics of patients. Different humoral and cellular changes have been reported in GSS, but lack sufficient supporting evidence. GSS is associated with angiomatous and lymphatic malformations. The changes in GSS and the theories of its pathophysiology may reveal. PMID- 27194111 TI - Curcumin Inhibits 5-Fluorouracil-induced Up-regulation of CXCL1 and CXCL2 of the Colon Associated with Attenuation of Diarrhoea Development. AB - The compound 5-fluorouracil (5-FU) is used in cancer chemotherapy and is known to cause diarrhoea. We recently reported that chemokine (C-X-C motif) ligand 1 (CXCL1) and neutrophils in the colonic mucosa were markedly increased by the administration of 5-FU in mice. Curcumin has anti-inflammatory, antitumour and antioxidant properties. Therefore, we examined the effect of curcumin on 5-FU induced diarrhoea development and CXCL1 and CXCL2 up-regulation in the colon. Mice were given 5-FU (50 mg/kg, i.p.) daily for 4 days. Curcumin (100 or 300 mg/kg, p.o.) was administered on the day before the first administration of 5-FU and administered 30 min. before the administration of 5-FU. Gene expression levels of CXCL1 and CXCL2 in the colon were examined by real-time RT-PCR. Curcumin reduced the 5-FU-induced diarrhoea development. Under this condition, the CXCL1 and CXCL2 gene up-regulated by 5-FU administration was inhibited by curcumin. The gene expression of CXCL1 and CXCL2 was also enhanced by 5-FU application in vitro. The 5-FU-induced up-regulated CXCL1 and CXCL2 gene expressions were inhibited by curcumin, Bay-117082 and bortezomib, nuclear factor kappa B (NF-kappaB) inhibitors, C646, a p300/cyclic adenosine monophosphate response element-binding protein-histone acetyltransferase (HAT) inhibitor. In conclusion, these findings suggested that curcumin prevented the development of diarrhoea by inhibiting NF-kappaB and HAT activation. PMID- 27194113 TI - Prohibited or regulated? LSD psychotherapy and the United States Food and Drug Administration. AB - Over the 1950s and early 1960s, the use of the hallucinogenic drug lysergic acid diethylamide (LSD) to facilitate psychotherapy was a promising field of psychiatric research in the USA. However, during the 1960s, research began to decline, before coming to a complete halt in the mid-1970s. This has commonly been explained through the increase in prohibitive federal regulations during the 1960s that aimed to curb the growing recreational use of the drug. However, closely examining the Food and Drug Administration's regulation of LSD research in the 1960s will reveal that not only was LSD research never prohibited, but that the administration supported research to a greater degree than has been recognized. Instead, the decline in research reflected more complex changes in the regulation of pharmaceutical research and development. PMID- 27194115 TI - Double Ring Expansion from an Aromatic [18]Porphyrin(1.1.1.1) to an Antiaromatic [20]Porphyrin(2.1.2.1). AB - Double ring expansion from a 5,15-diarylporphyrin to a 5,16-diaryl-10,11,21,22 tetradehydro[20]porphyrin(2.1.2.1) occurred through a reaction sequence consisting of oxidation with PbO2 to 5,15-dioxoporphodimethene, a Corey-Fuchs reaction with tetrabromomethane in the presence of triphenylphosphine, and Fritsch-Buttenberg-Wiechell rearrangement triggered by tert-butyllithium. The obtained tetradehydro[20]porphyrin(2.1.2.1) and its mono- and dihydrogenated congeners exhibited 20 pi antiaromatic character, whereas overhydrogenated congeners bearing a saturated bridge were nonaromatic owing to disrupted pi conjugation. PMID- 27194112 TI - Proteome-wide drug screening using mass spectrometric imaging of bead-arrays. AB - A fundamental challenge in the drug discovery process is to develop compounds with high efficacy and minimal side-effects. We describe a new approach to proteome-wide drug screening for detection of on- and off-target binding which combines the advantages of mass spectrometry with microarray technology. The method involves matrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI-MSI) of agarose micro-beads randomly arrayed at high-density in custom micro-well plates. Each bead carries a unique protein target and a corresponding photocleavable mass-tag for coding (PC-Mass-Tag). Compounds bound to specific protein beads and a photo-released coding PC-Mass-Tag are detected simultaneously using MALDI-MSI. As an initial demonstration of this approach, two kinase-targeted drugs, Dasatinib and Brigatinib (AP26113), were simultaneously screened against a model 50-member kinase-bead library. A MALDI-MSI scan performed at the equivalent density of 495,000 beads in the footprint of a microscope slide yielded 100% sensitivity for detecting known strong interactions with no false positives. PMID- 27194114 TI - Max Scheler's influence on Kurt Schneider. AB - Kurt Schneider (1887-1967) met Max Scheler (1874-1928) in 1919 when he enrolled in the latter's philosophy seminars at the University of Cologne. Kurt Schneider was then a junior psychiatrist and Max Scheler a renowned philosophy professor and co-founder of the phenomenological movement in philosophy. We uncover the facts about their intellectual and personal relationship, summarize the main articles and books that they wrote and consider whether Max Scheler did influence the young Kurt Schneider. We conclude that Scheler's philosophy of emotion impressed Schneider, and that the latter's notion of 'vital depression' as the core element in melancholia was essentially applied Schelerian philosophy. Schneider's more celebrated contributions to psychiatry - his notion of first rank symptoms of schizophrenia - owed nothing to Scheler or any other philosopher. PMID- 27194116 TI - Sexual identities and sexual health within the Celtic nations: An exploratory study of men who have sex with men recruited through social media. AB - Associations of sexual identity with a range of sexual and sexual health behaviours were investigated amongst men who have sex with men (MSM). Data from 1816 MSM recruited from 4 Celtic nations (Scotland, Wales, Northern Ireland and the Republic of Ireland) were collected via a cross-sectional online survey advertised via social media. About 18.3% were non-gay identified MSM (NGI-MSM). In the last year, 30% of NGI-MSM reported high-risk unprotected anal intercourse and 45% reported never having had an sexually transmitted infection (STI) test. When compared to MSM who were gay identified (GI-MSM), NGI-MSM were more likely to be older, have a female partner, fewer sex partners, fewer anal sex partners, STI diagnoses and less likely to be HIV positive, more likely to never use the gay scene and be geographically further from a gay venue. NGI-MSM were also less likely to report STI and HIV testing behaviours. The findings highlight variations in risk by sexual identities, and unmet sexual health needs amongst NGI-MSM across Celtic nations. Innovative research is required regarding the utility of social media for reaching populations of MSM and developing interventions which target the heterogeneity of MSM and their specific sexual health needs. PMID- 27194117 TI - Preclinical and human surrogate models of itch. AB - Pruritus, or simply itch, is a debilitating symptom that significantly decreases the quality of life in a wide range of clinical conditions. While histamine remains the most studied mediator of itch in humans, treatment options for chronic itch, in particular antihistamine-resistant itch, are limited. Relevant preclinical and human surrogate models of non-histaminergic itch are needed to accelerate the development of novel antipruritics and diagnostic tools. Advances in basic itch research have facilitated the development of diverse models of itch and associated dysaesthesiae. While experimental itch in humans is induced over a short period of time and usually assessed psychophysically, the study of itch reactions in animals allows for both short-term and long-term studies but relies heavily on behavioural assessments. This review provides a background and a presentation of the established models of itch currently applied in animals and humans with emphasis on translatability. PMID- 27194119 TI - Medical students and physical education students as CPR instructors: an appropriate solution to the CPR-instructor shortage in secondary schools? AB - BACKGROUND: Integrating cardiopulmonary resuscitation (CPR) training in secondary schools will increase the number of potential CPR providers. However, currently too few certified instructors are available for this purpose. Training medical students and physical education student teachers to become CPR instructors could decrease this shortage. AIM: Examine whether medical students and physical education student teachers can provide CPR training for secondary school pupils as well as (i. e., non-inferior to) registered nurses. METHODS: A total of 144 secondary school pupils were randomly assigned to CPR training by a registered nurse (n = 12), a medical student (n = 17) or a physical education student teacher (n = 15). CPR performance was assessed after training and after eight weeks in a simulated cardiac arrest scenario on a resuscitation manikin, using manikin software and video recordings. RESULTS: No significant differences were found between the groups on the overall Cardiff Test scores and the correctness of the CPR techniques during the post-training and retention test. All pupils showed sufficient CPR competence, even after eight weeks. CONCLUSION: Training by medical students or physical education student teachers is non-inferior to training by a registered nurse, suggesting that school teachers, student teachers and medical students can be recruited for CPR training in secondary schools. PMID- 27194118 TI - Pulmonary hypertension complicating pulmonary sarcoidosis. AB - Pulmonary hypertension (PH) is a severe complication of sarcoidosis, with an unknown prevalence. The aetiology is multifactorial, and the exact mechanism of PH in the individual patient is often difficult to establish. The diagnostic work up and treatment of PH in sarcoidosis is complex, and should therefore be determined by a multidisciplinary expert team in a specialised centre. It is still a major challenge to identify sarcoidosis patients at risk for developing PH. There is no validated algorithm when to refer a patient suspected for PH, and PH analysis itself is difficult. Until present, there is no established therapy for PH in sarcoidosis. Besides optimal treatment for sarcoidosis, case series evaluating new therapeutic options involving PH-targeted therapy are arising for a subgroup of patients. This review summarises the current knowledge regarding the aetiology, diagnosis and possible treatment options for PH in sarcoidosis. PMID- 27194120 TI - Comment on: Out-of-hospital cardiac arrest: the prospect of E-CPR in the Maastricht region. PMID- 27194122 TI - Generation of an inducible fibroblast cell line for studying direct cardiac reprogramming. AB - Direct reprogramming of fibroblasts into induced cardiomyocytes (iCMs) through forced expression of cardiac-lineage specific transcription factors holds promise as an alternative strategy for cardiac regeneration. To facilitate research in iCM reprogramming, we generated a suite of new tools. We developed a transformed cell line derived from mouse embryonic fibroblasts (MEF). This fibroblast cell line (MEF-T) harbors an alphaMHC-eGFP reporter transgene for rapid detection of newly derived iCMs. The MEF-T cell line is highly proliferative and easily transfected and transduced, making it an ideal tool for transgene expression and genetic manipulation. Additionally, we generated a Tet-On inducible polycistronic iCM reprogramming construct for the temporal regulation of reprogramming factor expression. Furthermore, we introduced this construct into MEF-T and created an inducible reprogrammable fibroblast cell line. These tools will facilitate future research in cell fate reprogramming by enabling the temporal control of reprogramming factor expression as well as high-throughput screening using libraries of small molecules, noncoding RNAs, and siRNAs. genesis 54:398-406, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27194123 TI - The Syrian refugees crisis brings challenges to the health authorities in Europe: hepatitis A virus is a case in point. PMID- 27194124 TI - Role of metastasectomy for recurrent/metastatic gastrointestinal stromal tumors based on an analysis of the Kinki GIST registry. AB - PURPOSE: To define the role of surgery for metastatic/recurrent lesions after resection of primary gastrointestinal stromal tumors (GISTs). METHODS: Based on data obtained from the Kinki GIST registry, patients with recurrence or metastasis were divided into a surgical treatment group (ST group), comprised those treated with surgery in addition to tyrosine kinase inhibitor (TKI) therapy; and a drug treatment group (DT group), comprised those treated with TKI therapy alone. We compared the baseline characteristics and survival outcomes of the groups. RESULTS: Metastasis or recurrence developed in 93 of the 737 patients with GISTs treated between 2003 and 2007, 50 (53.8 %) of whom were assigned to the ST group and 43 (46.2 %) to the DT group. In the ST group, the 5-year overall survival rate was significantly higher for patients who underwent R0/R1 resection than for those who underwent R2 resection (82.2 vs. 47.0 %, p = 0.018). Survival time after recurrence was correlated with the duration of total TKI therapy in both the ST and DT groups (r = 0.766 and r = 0.932, respectively, p < 0.001). CONCLUSIONS: Continuous TKI therapy appears to be important primarily for the prognostic improvement of patients with recurrent/metastatic GISTs. R0/R1 resection may have benefits when combined with TKI therapy for patients with stable disease or disease responsive to TKI therapy, less than four metastatic lesions, and lesions <100 mm in total. PMID- 27194125 TI - Outcomes of lung cancer surgery in patients with coronary artery disease: a decade of experience at a single institution. AB - PURPOSE: The aim of this study is to investigate the surgical outcomes of surgery for non-small cell lung cancer (NSCLC) in patients with coronary artery disease (CAD). METHODS: Among 805 patients who underwent surgery for NSCLC at our hospital within a recent 10-year period, 43 (5.3 %) had a history of CAD. We analyzed the surgical outcomes and risk factors for postoperative complications in these 43 patients. RESULTS: The postoperative mortality and morbidity rates were 2 and 42 %, respectively. The morbidity rate was significantly higher in the patients with CAD than in those without CAD (P < 0.01). Postoperative cerebrovascular or cardiovascular events occurred in four patients (9 %). Having two of the following was significantly associated with the development of postoperative complications: decreased cardiac function, respiratory dysfunction, or deteriorated renal function (p = 0.04). The 5-year overall and disease-free survival rates of the patients with CAD were 75.6 and 64.5 %, respectively; comparable with those of the patients without CAD; at 77.9 % and 72.5 %, respectively (p = 0.46 and 0.69). CONCLUSIONS: Patients with NSCLC and a history of CAD are at higher risk of complications after pulmonary resection. Combined decreased organ function is a risk factor for postoperative complications. CAD did not influence the long-term outcomes of patients after pulmonary resection for NSCLC. PMID- 27194127 TI - On the gas phase fragmentation of protonated uracil: a statistical perspective. AB - The potential energy surface of protonated uracil has been explored by an automated transition state search procedure, resulting in the finding of 1398 stationary points and 751 reactive channels, which can be categorized into isomerizations between pairs of isomers, unimolecular fragmentations and bimolecular reactions. The use of statistical Rice-Ramsperger-Kassel-Marcus (RRKM) theory and Kinetic Monte Carlo (KMC) simulations allowed us to determine the relative abundances of each fragmentation channel as a function of the ion's internal energy. The KMC/RRKM product abundances are compared with novel mass spectrometry (MS) experiments in the collision energy range 1-6 eV. To facilitate the comparison between theory and experiments, further dynamics simulations are carried out to determine the fraction of collision energy converted into the ion's internal energy. The KMC simulations show that the major fragmentation channels are isocyanic acid and ammonia losses, in good agreement with experiments. The third predominant channel is water loss according to both theory and experiments, although the abundance obtained in the KMC simulations is very low, suggesting that non-statistical dynamics might play an important role in this channel. Isocyanic acid (HNCOH(+)) is also an important product in the KMC simulations, although its abundance is only significant at internal energies not accessible in the MS experiments. PMID- 27194128 TI - Terahertz Modulator based on Metamaterials integrated with Metal-Semiconductor Metal Varactors. AB - The terahertz (THz) band of the electromagnetic spectrum, with frequencies ranging from 300 GHz to 3 THz, has attracted wide interest in recent years owing to its potential applications in numerous areas. Significant progress has been made toward the development of devices capable of actively controlling terahertz waves; nonetheless, further advances in device functionality are necessary for employment of these devices in practical terahertz systems. Here, we demonstrate a low voltage, sharp switching terahertz modulator device based on metamaterials integrated with metal semiconductor metal (MSM) varactors, fabricated on an AlGaAs/InGaAs based heterostructure. By varying the applied voltage to the MSM varactor located at the center of split ring resonator (SRR), the resonance frequency of the SRR-based metamaterial is altered. Upon varying the bias voltage from 0 V to 3 V, the resonance frequency exhibits a transition from 0.52 THz to 0.56 THz, resulting in a modulation depth of 45 percent with an insertion loss of 4.3 dB at 0.58 THz. This work demonstrates a new approach for realizing active terahertz devices with improved functionalities. PMID- 27194126 TI - Postoperative analgesia using fentanyl plus celecoxib versus epidural anesthesia after laparoscopic colon resection. AB - PURPOSE: Effective postoperative analgesia is essential to a patient's recovery after laparoscopic colon resection (LCR). We introduce a new analgesic protocol using fentanyl plus celecoxib following LCR. METHODS: The subjects of this retrospective comparative study were 137 patients who underwent LCR, 63 of whom were treated with 72 h of epidural anesthesia (group E), and 74 of whom were treated with 24 h of fentanyl intravenous injection followed by 7 days of oral celecoxib (group FC). We evaluated the safety and efficacy of this new protocol. RESULTS: The combination of fentanyl and celecoxib maintained a low postoperative pain score (<1.5, evaluated by the FACES Pain Scale) and reduced the need for rescue analgesic drugs for 7 days (groups E vs. FC: 5.39 +/- 3.77 vs. 2.79 +/- 2.92, p < 0.001). The postoperative hospital stay was almost equal for the two groups (E vs. FC: 11.1 +/- 4.5 vs. 10.3 +/- 4.8 days, p = 0.315). The operating room stay other than for surgery was significantly shorter for group FC (E vs. FC: 128.7 +/- 30.5 vs. 107.2 +/- 17.0 min, p < 0.001). Neither group experienced complications, apart from one group FC patient, who suffered transient nausea and vertigo. CONCLUSIONS: The new analgesic protocol using fentanyl plus celecoxib is an effective and time-saving strategy for LCR. PMID- 27194129 TI - Performance of the IOTA ADNEX model in preoperative discrimination of adnexal masses in a gynecological oncology center. AB - OBJECTIVE: To evaluate the performance of the International Ovarian Tumor Analysis (IOTA) ADNEX model in the preoperative discrimination between benign ovarian (including tubal and para-ovarian) tumors, borderline ovarian tumors (BOT), Stage I ovarian cancer (OC), Stage II-IV OC and ovarian metastasis in a gynecological oncology center in Brazil. METHODS: This was a diagnostic accuracy study including 131 women with an adnexal mass invited to participate between February 2014 and November 2015. Before surgery, pelvic ultrasound examination was performed and serum levels of tumor marker CA 125 were measured in all women. Adnexal masses were classified according to the IOTA ADNEX model. Histopathological diagnosis was the gold standard. Receiver-operating characteristics (ROC) curve analysis was used to determine the diagnostic accuracy of the model to classify tumors into different histological types. RESULTS: Of 131 women, 63 (48.1%) had a benign ovarian tumor, 16 (12.2%) had a BOT, 17 (13.0%) had Stage I OC, 24 (18.3%) had Stage II-IV OC and 11 (8.4%) had ovarian metastasis. The area under the ROC curve (AUC) was 0.92 (95% CI, 0.88 0.97) for the basic discrimination between benign vs malignant tumors using the IOTA ADNEX model. Performance was high for the discrimination between benign vs Stage II-IV OC, BOT vs Stage II-IV OC and Stage I OC vs Stage II-IV OC, with AUCs of 0.99, 0.97 and 0.94, respectively. Performance was poor for the differentiation between BOT vs Stage I OC and between Stage I OC vs ovarian metastasis with AUCs of 0.64. CONCLUSION: The majority of adnexal masses in our study were classified correctly using the IOTA ADNEX model. On the basis of our findings, we would expect the model to aid in the management of women with an adnexal mass presenting to a gynecological oncology center. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 27194130 TI - Health-related quality of life in patients with spinal dural arteriovenous fistulae. AB - Neurological improvement in patients with spinal dural arteriovenous fistulae (SDAVF) is often partial even after adequate treatment. While treatment outcomes have been evaluated primarily on the basis of the postoperative changes in neurological deficits, outcome measures should also reflect the patient-reported outcome (PRO). We conducted a health-related quality of life (HRQOL) survey in 52 SDAVF patients; 33 (63.5%) completed the short-form 36 Health Survey (SF-36) questionnaire. They were 25 males and 8 females ranging in age from 47 to 85 years (mean age 70.0 years). The mean follow-up period was 95.6 months. We analyzed the completed questionnaires and examined the clinical factors associated with their HRQOL. After treatment, gait- and micturition disturbances persisted in 31 (93.9%) and 31 (93.9%) of our patients; 26 (78.8%) reported chronic leg pain. The SF-36 scores of treated SDAVF patients were significantly lower than the national average of 50 for all 8 sub-items in the questionnaire. The scores for physical functioning (PF) and role-physical (RP) were particularly low. With the exception of bodily pain (BP), there was a significant negative correlation between the Aminoff-Logue scale (ALS) scores for gait- and micturition and the sub-item scores. The score for BP showed a significant positive correlation with the scores for the 7 other SF-36 sub-items. The HRQOL of treated SDAVF patients was lower than the national average with respect to both physical and mental aspects. Persistent post-treatment pain and gait- and micturition disturbances were responsible for their lower HRQOL. PMID- 27194131 TI - The masaryk hospital extracranial-intracranial bypass study. AB - Patients with symptomatic internal carotid artery (ICA) occlusion with haemodynamic impairment are at higher risk of ischaemic stroke, and they require treatment. There are two main options: the best medical treatment and an extracranial-intracranial bypass. The aims of this study are to analyse the 30 day and 2-year risk of stroke and death in patients with extracranial intracranial bypass performed by our department and to compare our results with major published studies. This retrospective study enrolled patients who underwent surgery from 1998 to 2012. Inclusion criteria were the following: (1) radiological diagnosis of symptomatic atherosclerotic internal carotid artery occlusion (AICAO), (2) less than 50 % stenosis of a contralateral ICA, (3) transient ischaemic attack (TIA) or ischaemic stroke in the hemispheric territory on an occluded side within 120 days and (4) haemodynamic impairment of at least stage I according to transcranial Doppler sonography (TCDS), perfusion CT and SPECT. Patients were followed up in the outpatient department with TCDS and sonography of the contralateral ICA and the anastomosis after 6 weeks and every 12 months after that. All risks of stroke and death from surgery were recorded throughout the 30 days and the following 2 years post surgery. From September 1998 to November 2012, 93 patients were selected for bypass surgery. There were 72 men and 21 women in an age range of 33 to 79 years (mean 58.9 years) and a follow-up range of 13 to 187 months (mean 108 months). The 30-day risk of stroke and death was 7.5 %. It consists of one death, one major ischaemic stroke, two reversible neurological deficits and three TIAs. The 2-year risk of stroke and death was 9.7 %. Extracranial-intracranial bypass is an effective treatment of haemodynamic impairment in patients with internal carotid occlusion. Maintaining low-level morbidity and mortality is possible with a dedicated neurovascular team. This is the only way in which we can reduce the risk of stroke and death in patients with bypass compared to patients treated medically. PMID- 27194132 TI - Proposal of an optimized strategy for intraoperative testing of speech and language during awake mapping. AB - In this paper, we review the literature about the definitions of errors observed by direct electrical stimulation during language testing. As a practical application, we propose an optimized strategy for differentiating accurately motor arrest, speech arrest, and anomia in the context of intraoperative mapping. Finally, we also discuss the anatomical correlates of the networks sustaining these different errors, both cortically and axonally. PMID- 27194133 TI - Detailed anatomy knowledge: first step to approach petroclival meningiomas through the petrous apex. Anatomy lab experience and surgical series. AB - Petroclival meningiomas are a challenge for neurosurgeons due to the complex anatomy of the region that is rich of vessels and nerves. A perfect and detailed knowledge of the anatomy is very demanding in neurosurgery, especially in skull base surgery. The authors describe the microsurgical anatomy to perform an anterior petrosectomy based on their anatomical and surgical experience and perform a literature review. The temporal bone is the most complex and fascinating bone of skull base. The apex is located in the angle between the greater wing of the sphenoid and the occipital bone. Removing the petrous apex exposes the clivus. The approach directed through the temporal bone in this anatomical area is referred to as an anterior petrosectomy. The area that must be drilled is the rhomboid fossa that is defined by the Kawase, premeatal, and postmeatal triangles. In Division of Neurosurgery - University of Turin, 130 patients, from August 2013 to September 2015, underwent surgical resection of intracranial meningiomas. In this group, we have operated 7 PCMs and 5 of these were approached performing an anterior petrosectomy with good results. In our conclusions, we feel that this surgery require an advanced knowledge of human anatomy and a specialized training in interpretation of radiological and microsurgical anatomy both in the dissection lab and in the operating room. PMID- 27194134 TI - Mobile Phones and Psychosocial Therapies with Vulnerable People: a First State of the Art. AB - Mobile phones are becoming a communication tool commonly used by people all over the world; and they are started to be adopted in psychosocial therapies involving vulnerable people. We are herein presenting the results of an academic literature review. We identified scientific papers published between 2006 and 2015 resorting to academic databases available on the Internet, applying a systematic selection method based on quality criteria. Secondly, we analysed contents, highlighting the scarcity of research involving vulnerable people. The available literature specialized in psychosocial therapies offers investigation results which involve mobile phones and patients in general, focusing particularly on the clinical psychology field and, to a lesser extent, on the social work field. Particularly significant are the investigation works developed in the United States. In the present paper we introduce a first "state of the art", identifying opportunities and also the limitations surrounding the use of mobile phones in psychosocial therapies targeting the vulnerable. Issues concerning privacy and data confidentiality, and the access of vulnerable people to mobile phones and how they use them, pose significant challenges; but they offer the opportunity to reach isolated or impoverished populations, or even to facilitate access to social and healthcare services. We close this paper formulating possible orientations, hypotheses and goals to design new investigation works involving vulnerable populations. PMID- 27194135 TI - Overexpression of the beta2AR gene improves function and re-endothelialization capacity of EPCs after arterial injury in nude mice. AB - BACKGROUND: Proliferation and migration of endothelial progenitor cells (EPCs) play important roles in restoring vascular injuries. beta2 adrenergic receptors (beta2ARs) are widely expressed in many tissues and have a beneficial impact on EPCs regulating neoangiogenesis. The aim of the present study was to determine the effect of overexpressing beta2ARs in infused peripheral blood (PB)-derived EPCs on the re-endothelialization in injured vessels. METHODS: Induction of endothelial injury was performed in male nude mice that were subjected to wire mediated injury to the carotid artery. Human PB-derived EPCs were transfected with an adenovirus serotype 5 vector expressing beta2AR (Ad5/beta2AR-EPCs) and were examined 48 h later. beta2AR gene expression in EPCs was detected by real time polymerase chain reaction and Western blot analysis. In vitro, the proliferation, migration, adhesion, and nitric oxide production of Ad5/beta2AR EPCs were measured. Meanwhile, phosphorylated Akt and endothelial nitric oxide synthase (eNOS), which are downstream of beta2AR signaling, were also elevated. In an in vivo study, CM-DiI-labeled EPCs were injected intravenously into mice subjected to carotid injury. After 3 days, cells recruited to the injury sites were detected by fluorescent microscopy, and the re-endothelialization was assessed by Evans blue dye. RESULTS: In vitro, beta2AR overexpression augmented EPC proliferation, migration, and nitric oxide production and enhanced EPC adhesion to endothelial cell monolayers. In vivo, when cell tracking was used, the number of recruited CM-DiI-labeled EPCs was significantly higher in the injured zone in mice transfused with Ad5/beta2AR-EPCs compared with non transfected EPCs. The degree of re-endothelialization was also higher in the mice transfused with Ad5/beta2AR-EPCs compared with non-transfected EPCs. We also found that the phosphorylation of Akt and eNOS was increased in Ad5/beta2AR-EPCs. Preincubation with beta2AR inhibitor (ICI118,551), Akt inhibitor (ly294002), or eNOS inhibitor (L-NAME) significantly attenuated the enhanced in vitro function and in vivo re-endothelialization capacity of EPCs induced by beta2AR overexpression. CONCLUSIONS: The present study demonstrates that beta2AR overexpression enhances EPC functions in vitro and enhances the vascular repair abilities of EPCs in vivo via the beta2AR/Akt/eNOS pathway. Upregulation of beta2AR gene expression through gene transfer may be a novel therapeutic target for endothelial repair. PMID- 27194136 TI - Enhanced antibiotic distribution strategies and the potential impact of facial cleanliness and environmental improvements for the sustained control of trachoma: a modelling study. AB - BACKGROUND: Despite some success in controlling trachoma with repeated mass drug administration (MDA), some hyperendemic regions are not responding as fast as anticipated. Available data suggests that individuals with higher bacterial infection loads are less likely to resolve infection following a single dose of treatment, and thus remain a source of re-emergent infection following treatment. We assessed the potential impact of a new double-dose antibiotic distribution strategy in addition to enhanced facial cleanliness (F) and environmental improvements (E). METHODS: Using a within-community mathematical model of trachoma transmission we assessed the impact of a new double-dose antibiotic distribution strategy given 2 weeks apart, with and without enhanced F&E. We compared the annual double-dose strategy to single-dose annual MDA treatment in hyper-, meso- and hypoendemic settings, and to biannual MDA at 6-monthly intervals in hyperendemic communities. RESULTS: The findings from our mathematical model suggest that implementing the new double-dose strategy for 5 years or less was predicted to control infection more successfully than annual or 6-monthly treatment. Infection was controlled more readily if treatment was combined with enhanced F&E. The results appeared robust to variation in a number of key epidemiological parameters. To have long-term impact on transmission, enhanced F&E is essential for high transmission settings. CONCLUSION: Our current findings are based on simualtion modelling only, due to lack of epidemilogical data, however they do suggest that the annual double-dose treatment strategy is encouraging for trachoma control. In high transmission settings, both MDA and enhanced F&E are needed for sustained control. PMID- 27194137 TI - Pulmonary and pleural lymphatic endothelial cells from pediatric, but not adult, patients with Gorham-Stout disease and generalized lymphatic anomaly, show a high proliferation rate. AB - BACKGROUND: Gorham-Stout disease (OMIM 123880) and generalized lymphatic anomaly are two rare disorders of lymphendothelial growth in which thoracic involvement with chylothorax is a feared complication. Currently it is believed that both disorders are prenatal malformations that progress slowly after birth. Several pharmaceuticals with antiproliferative properties, including interferon-alpha-2b, rapamycin and propranolol, have however been shown to affect the disease course in some patients. Deeper knowledge of the growth characteristics of these malformations are therefore needed to guide the clinical approach. METHODS: Lymphatic vessels in lung and pleural tissue from both children and adult patients with generalized lymphatic anomaly or Gorham-Stout disease were studied using an immunohistochemical approach, targeting lymphendothelial markers (D2 40/Prox-1) and a proliferation marker (Ki-67). RESULTS: We found significant proliferation and growth in these lesions in pediatric patients but not in adults. Furthermore, the data may suggest that the disease process is at least partly reversible. CONCLUSIONS: These malformations of the lymphatic system proliferate at a significant rate long after birth, which could suggest that the clinical approach for children should be different from adults. PMID- 27194138 TI - [IF-RT alone remains gold standard for stage IA nodular lymphocyte-predominant Hodgkin lymphoma]. PMID- 27194140 TI - Research and partnerships with schools. AB - PURPOSE: Despite the quantity of research on child and adolescent mental health being done in schools, little output has focused on the practical aspects of recruiting schools and students into a study. Furthermore, there is limited knowledge on how to develop and sustain productive and mutually beneficial partnerships with schools after the project finishes. METHODS: A large study examining prevalence of mental health problems in young people involving nine schools is used as an example for the procedure of recruitment and carrying out a research project, while developing and sustaining partnerships with schools. RESULTS: While recruiting the schools, a three-stage model was developed that corresponded closely to the school's needs and existing demands. The suggested procedure for the study, thus, closely reflected the varying existing cultures of participating schools. Partnerships, developed as a result of the project, were used in developing further projects and interventions for promoting good mental health in schools. CONCLUSIONS: Rather than a blanket research recruitment and procedural approach with an end to school involvement at the end of the project, the paper advocates for a deeper understanding of the schools' internal culture for improved recruitment and study outcomes. Developed partnerships, when sustained past the completion of research, prove to be a useful tool in applying the findings in promoting good mental health in schools and continuing research further. PMID- 27194139 TI - Thoracic Pedicle Screw Placement Guide Plate Produced by Three-Dimensional (3-D) Laser Printing. AB - BACKGROUND The aim of this study was to evaluate the accuracy and feasibility of an individualized thoracic pedicle screw placement guide plate produced by 3-D laser printing. MATERIAL AND METHODS Thoracic pedicle samples of 3 adult cadavers were randomly assigned for 3-D CT scans. The 3-D thoracic models were established by using medical Mimics software, and a screw path was designed with scanned data. Then the individualized thoracic pedicle screw placement guide plate models, matched to the backside of thoracic vertebral plates, were produced with a 3-D laser printer. Screws were placed with assistance of a guide plate. Then, the placement was assessed. RESULTS With the data provided by CT scans, 27 individualized guide plates were produced by 3-D printing. There was no significant difference in sex and relevant parameters of left and right sides among individuals (P>0.05). Screws were placed with assistance of guide plates, and all screws were in the correct positions without penetration of pedicles, under direct observation and anatomic evaluation post-operatively. CONCLUSIONS A thoracic pedicle screw placement guide plate can be produced by 3-D printing. With a high accuracy in placement and convenient operation, it provides a new method for accurate placement of thoracic pedicle screws. PMID- 27194141 TI - Production of cyclodextrin glycosyltransferase by immobilized Bacillus sp. on chitosan matrix. AB - The whole-cell immobilization on chitosan matrix was evaluated. Bacillus sp., as producer of CGTase, was grown in solid-state and batch cultivation using three types of starches (cassava, potato and cornstarch). Biomass growth and substrate consumption were assessed by flow cytometry and modified phenol-sulfuric acid assays, respectively. Qualitative analysis of CGTase production was determined by colorless area formation on solid culture containing phenolphthalein. Scanning electron microscopy (SEM) analysis demonstrated that bacterial cells were immobilized on chitosan matrix efficiently. Free cells reached very high numbers during batch culture while immobilized cells maintained initial inoculum concentration. The maximum enzyme activity achieved by free cells was 58.15 U ml( 1) (36 h), 47.50 U ml(-1) (36 h) and 68.36 U ml(-1) (36 h) on cassava, potato and cornstarch, respectively. CGTase activities for immobilized cells were 82.15 U ml(-1) (18 h) on cassava, 79.17 U ml(-1) (12 h) on potato and 55.37 U ml(-1) (in 6 h and max 77.75 U ml(-1) in 36 h) on cornstarch. Application of immobilization technique increased CGTase activity significantly. The immobilized cells produced CGTase with higher activity in a shorter fermentation time comparing to free cells. PMID- 27194142 TI - Robotic and open partial nephrectomy for complex renal tumors: a matched-pair comparison with a long-term follow-up. AB - OBJECTIVES: To compare the surgical, functional and oncological outcomes of patients undergoing robotic partial nephrectomy (RPN) or open partial nephrectomy (OPN) for moderately or highly complex tumors (RENAL nephrometry score >=7). METHODS: A retrospective, matched-pair analysis was performed for 380 patients who underwent either RPN (n = 190) or OPN (n = 190) for a complex renal mass in different institutions. Surgical data, pathological variables, complications and functional and oncological outcomes were reviewed. RESULTS: RPN is associated with less estimated blood loss (EBL) (196.8 vs 240.8 ml; p < 0.001), shorter length of hospital stay (7.8 vs 9.2 days; p < 0.001) and lower rate of postoperative complications (15.8 vs 28.9 %; p = 0.002). Patients undergoing RPN required more direct cost. In multivariable models, surgical approach was the significant predictor for the occurrence of postoperative minor complications and postoperative wound pain. Median follow-up for RPN and OPN was 49 months and 52 months, respectively. The decline of estimated glomerular filtration at the last available follow-up (RPN: 8.7 %; OPN: 10 %) was similar (p = 0.125). The 5-year recurrence-free survival rate was 95.1 % for RPN and 92.7 % for OPN (p = 0.48). CONCLUSIONS: RPN provides acceptable and comparable results in terms of perioperative, functional and oncological outcomes compared to OPN for complex renal tumors with RENAL score >=7. Moreover, RPN is a less invasive approach with the benefit of shorter length of hospital stay, less EBL and lower rate of postoperative complications. PMID- 27194143 TI - Predictive value of neutrophil-lymphocyte ratio in renal cancer. PMID- 27194144 TI - Maximizing Team Performance: The Critical Role of the Nurse Leader. AB - Facilitating team development is challenging, yet critical for ongoing improvement across healthcare settings. The purpose of this exemplary case study is to examine the role of nurse leaders in facilitating the development of a high performing Change Team in implementing a patient safety initiative (TeamSTEPPs) using the Tuckman Model of Group Development as a guiding framework. The case study is the synthesis of 2.5 years of critical access hospital key informant interviews (n = 50). Critical juncture points related to team development and key nurse leader actions are analyzed, suggesting that nurse leaders are essential to maximize clinical teams' performance. PMID- 27194145 TI - Extracellular vesicles derived from human vestibular schwannomas associated with poor hearing damage cochlear cells. AB - BACKGROUND: Vestibular schwannoma (VS) is a tumor of the vestibular nerve that transmits balance information from the inner ear to the brain. Sensorineural hearing loss occurs in 95% of patients with these tumors, but the cause of this loss is not well understood. We posit a role of VS-secreted extracellular vesicles (EVs) as a major contributing factor in cochlear nerve damage. METHODS: Using differential centrifugation, we isolated EVs from VS cell line HEI-193 and primary cultured human VS cells from patients with good hearing or poor hearing. The EVs were characterized using a Nanosight device and transmission electron microscopy and by extracting their RNA content. The EVs' effects on cultured murine spiral ganglion cells and organotypic cochlear cultures were studied using a transwell dual-culture system and by direct labeling of EVs with PKH-67 dye. EV induced changes in cochlear cells were quantified using confocal immunohistochemistry. Transfection of VS cells with a green fluorescent protein containing plasmid was confirmed with reverse transcription PCR. RESULTS: Human VS cells, from patients with poor hearing, produced EVs that could damage both cultured murine cochlear sensory cells and neurons. In contrast, EVs derived from VS cells from patients with good hearing did not damage the cultured cochlear cells. CONCLUSIONS: This is the first report on EVs derived from VSs and on the capacity of EVs from VSs from patients with hearing loss to selectively damage cochlear cells, thereby identifying a potential novel mechanism of VS-associated sensorineural hearing loss. PMID- 27194146 TI - Systemic AAV9-IFNbeta gene delivery treats highly invasive glioblastoma. AB - BACKGROUND: Complete surgical removal of all glioblastoma (GBM) cells is impossible due to extensive infiltration into brain parenchyma that ultimately leads to tumor recurrence. The current standard of care affords modest improvements in survival. New therapeutic interventions are needed to prevent recurrence. Local AAV-hIFNbeta gene delivery to the brain was previously shown to eradicate noninvasive orthotopic U87 tumors in mice. However, widespread CNS gene delivery may be necessary to treat invasive GBMs. Here we investigated the therapeutic effectiveness of systemically infused AAV9-hIFNbeta against an invasive orthotopic GBM8 model. METHODS: Mice bearing human GBM8 brain tumors expressing firefly luciferase (Fluc) were treated systemically with different doses of scAAV9-hIFNbeta vector. Therapeutic efficacy was assessed by sequential bioluminescence imaging of tumor Fluc activity and animal survival. Brains were analyzed post mortem for the presence and appearance of tumors. Two transcriptionally restricted AAV vectors were used to assess the therapeutic contribution of peripheral hIFNbeta. RESULTS: Systemic infusion of scAAV9 hIFNbeta vector induced complete regression of established GBM8 tumors in a dose dependent manner. The efficacy of this approach was also dependent on the stage of tumor growth at the time of treatment. We also showed that peripherally produced hIFNbeta contributed considerably to the therapeutic effect of scAAV9 hIFNbeta. A comparative study of systemic and unilateral intracranial delivery of scAAV9-hIFNbeta in a bilateral GBM8 tumor model showed the systemic route to be the most effective approach for treating widely dispersed tumors. CONCLUSIONS: Systemic delivery of AAV9-IFNbeta is an attractive approach for invasive and multifocal GBM treatment. PMID- 27194147 TI - Reporting of patient-reported health-related quality of life in adults with diffuse low-grade glioma: a systematic review. AB - BACKGROUND: Patient-reported health-related quality of life (HRQoL) analysis can provide important information for managing the balance between treatment benefits and treatment-related adverse effects on quality of life (QoL). This systematic review sought to identify the range of HRQoL measures used for patients with diffuse hemispheric WHO grade II glioma (DLGG) and assess the quality of HRQoL reporting. METHODS: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Databases were searched for full-text English articles reporting HRQoL outcomes in adult patients with DLGG. RESULTS: Eleven different QoL measures were used across the 26 included studies, none of which has been validated in patients with DLGG. Heterogeneity of study design prevented pooled analysis of data investigating the effect of interventions or establishing long term HRQoL. Low rates of participation at baseline (mean: 64.0%) and high rates of subsequent dropout (2.1% per month) were identified. Five studies gave statistical methods to deal with missing data or provided evidence of clinical significance of HRQoL results. CONCLUSIONS: The results demonstrate a paucity and heterogeneity of reporting of HRQoL in the DLGG literature, highlighting the need for a standardized assessment schedule and set of validated quality-of-life measures for future studies. PMID- 27194150 TI - Capsule Commentary on Kimerling et al., Prevalence of Intimate Partner Violence among Women Veterans who Utilize Veterans Health Administration Primary Care. PMID- 27194151 TI - Use of Video Decision Aids to Promote Advance Care Planning in Hilo, Hawai'i. AB - INTRODUCTION: Advance care planning (ACP) seeks to promote care delivery that is concordant with patients' informed wishes. Scalability and cost may be barriers to widespread ACP, and video decision aids may help address such barriers. AIM: Our primary hypothesis was that ACP documentation would increase in Hilo after ACP video implementation. Secondary hypotheses included increased use of hospice, fewer deaths in the hospital, and decreased costs in the last month of life. SETTING: The city of Hilo in Hawai'i (population 43,263), which is served by one 276-bed hospital (Hilo Medical Center), one hospice (the Hospice of Hilo), and 30 primary care physicians. PROGRAM DESCRIPTION: The intervention consisted of a single, 1- to 4-h training and access to a suite of ACP video decision aids. PROGRAM EVALUATION: Prior to implementation, the rate of ACP documentation for hospitalized patients with late-stage disease was 3.2 % (11/346). After the intervention, ACP documentation was 39.9 % (1,107/2,773) (P < 0.001). Primary care providers in the intervention had an ACP completion rate for patients over 75 years of 37.0 % (1,437/3,888) compared to control providers, who had an average of 25.6 % (10,760/42,099) (P < 0.001). The rate of discharge from hospital to hospice for patients with late-stage disease was 5.7 % prior to the intervention and 13.8 % after the intervention (P < 0.001). The average total insurance cost for the last month of life among Hilo patients was $3,458 (95 % CI $3,051 to 3,865) lower per patient after the intervention when compared to the control region. DISCUSSION: Implementing ACP video decision aids was associated with improved ACP documentation, greater use of hospice, and decreased costs. Decision aids that promote ACP offer a scalable and cost-efficient medium to place patients at the center of their care. PMID- 27194152 TI - Is it effective to use the crushing technique in all types of concha bullosa. AB - A prospective study to evaluate long term results of crushing technique in concha bullosa surgery with radiographic and endoscopic methods and to determine the type of concha bullosa in which crushing technique is more effective. 71 patients who underwent concha bullosa surgery with septoplasty were included in the study. All concha bullosa were divided into three groups according to their types (Group 1 lamellar type, Group 2 bulbous type, Group 3 extensive type). Crushing of the pneumatized middle turbinate was done under endoscopic view. All the patients had an endoscopic nasal examination and middle turbinates were photographed and axial and coronal paranasal computed tomography (CT) scans were taken before the surgery and approximately 2 years after the surgery. Preoperative and postoperative measurements were compared using paired t test and One-way ANOVA. Mean age of the 71 patients were as follows: 38 males, mean age 30.2 (range 20 44) years; 33 females, mean age 27.6 (range 18-40) years. The patients were followed for 22.7 (range 20-26) months. In all groups, the postoperative endoscopic grading scores and CT volumes were significantly reduced (p < 0.0001). Comparison between groups showed significant post operative reduction in both CT volumes and in endoscopic scoring for group 2 (bulbous type) (p < 0.0001). Crushing is a simple and safe method in concha bullosa surgery. There was no recurrance in long-term outcomes. This method can be used in all types of concha bullosa effectively and provides more volume reduction in bulbous type concha bullosa. PMID- 27194148 TI - Final results of the second prospective AIEOP protocol for pediatric intracranial ependymoma. AB - BACKGROUND: This prospective study stratified patients by surgical resection (complete = NED vs incomplete = ED) and centrally reviewed histology (World Health Organization [WHO] grade II vs III). METHODS: WHO grade II/NED patients received focal radiotherapy (RT) up to 59.4 Gy with 1.8 Gy/day. Grade III/NED received 4 courses of VEC (vincristine, etoposide, cyclophosphamide) after RT. ED patients received 1-4 VEC courses, second-look surgery, and 59.4 Gy followed by an 8-Gy boost in 2 fractions on still measurable residue. NED children aged 1-3 years with grade II tumors could receive 6 VEC courses alone. RESULTS: From January 2002 to December 2014, one hundred sixty consecutive children entered the protocol (median age, 4.9 y; males, 100). Follow-up was a median of 67 months. An infratentorial origin was identified in 110 cases. After surgery, 110 patients were NED, and 84 had grade III disease. Multiple resections were performed in 46/160 children (28.8%). A boost was given to 24/40 ED patients achieving progression-free survival (PFS) and overall survival (OS) rates of 58.1% and 68.7%, respectively, in this poor prognosis subgroup. For the whole series, 5 year PFS and OS rates were 65.4% and 81.1%, with no toxic deaths. On multivariable analysis, NED status and grade II were favorable for OS, and for PFS grade II remained favorable. CONCLUSIONS: In a multicenter collaboration, this trial accrued the highest number of patients published so far, and results are comparable to the best single-institution series. The RT boost, when feasible, seemed effective in improving prognosis. Even after multiple procedures, complete resection confirmed its prognostic strength, along with tumor grade. Biological parameters emerging in this series will be the object of future correlatives and reports. PMID- 27194153 TI - Reduced task-related functional connectivity during a set-shifting task in unmedicated early-stage Parkinson's disease patients. AB - BACKGROUND: Patients with Parkinson's disease (PD) often suffer from cognitive impairments, including set-shifting deficits, in addition to the characteristic motor symptoms. It is hypothesized that the striatal dopamine depletion leads to a sub-optimal functional connectivity between task-related brain areas and consequently results in impaired task-performance. In this study, we aimed to examine this hypothesis by investigating the task-related functional connectivity of brain areas that are believed to be involved in set-shifting, such as the dorsolateral prefrontal cortex (DLPFC), posterior parietal cortex (PPC) and the superior frontal gyrus (SFG), during a set-shifting task. We obtained functional imaging data from 18 early-stage PD patients and 35 healthy controls, matched at the group level, using a newly developed rule-based set-shifting task that required participants to manually respond to arrow stimuli based on their location on the screen of their direction. RESULTS: We found that early stage PD patients, compared with controls, showed (1) a decrease in positive coupling between the left DLPFC and the right insular cortex, and the right SFG and anterior cingulate cortex, (2) an increase in negative coupling between the right SFG and the anterior cingulate cortex, primary motor cortex, precuneus, and PPC, and (3) an increase in negative coupling between the left DLPFC and the left and right SFG. These results indicate that important task-related areas of PD patients have decreased functional connectivity with task-related regions and increased connectivity with task-unrelated areas. CONCLUSIONS: The disruption of functional connectivity in early stage PD patients during set-shifting reported here is likely compensated for by the local hyperactivation we reported earlier, thereby forestalling behavioural deficits. PMID- 27194156 TI - Suicide methods in children and adolescents. AB - There are notable differences in suicide methods between countries. The aim of this paper is to analyse and describe suicide methods in children and adolescents aged 10-19 years in different countries/territories worldwide. Suicide data by ICD-10 X codes were obtained from the WHO Mortality Database and population data from the World Bank. In total, 101 countries or territories, have data at least for 5 years in 2000-2009. Cluster analysis by suicide methods was performed for countries/territories with at least 10 suicide cases separately by gender (74 for males and 71 for females) in 2000-2009. The most frequent suicide method was hanging, followed by poisoning by pesticides for females and firearms for males. Cluster analyses of similarities in the country/territory level suicide method patterns by gender identified four clusters for both gender. Hanging and poisoning by pesticides defined the clusters of countries/territories by their suicide patterns in youth for both genders. In addition, a mixed method and a jumping from height cluster were identified for females and two mixed method clusters for males. A number of geographical similarities were observed. Overall, the patterns of suicide methods in children and adolescents reflect lethality, availability and acceptability of suicide means similarly to country specific patterns of all ages. Means restriction has very good potential in preventing youth suicides in different countries. It is also crucial to consider cognitive availability influenced by sensationalised media reporting and/or provision of technical details about specific methods. PMID- 27194155 TI - An Examination of Sources of Variability Across the Consonant-Nucleus-Consonant Test in Cochlear Implant Listeners. AB - The 10 consonant-nucleus-consonant (CNC) word lists are considered the gold standard in the testing of cochlear implant (CI) users. However, variance in scores across lists could degrade the sensitivity and reliability of them to identify deficits in speech perception. This study examined the relationship between variability in performance among lists and the lexical characteristics of the words. Data are from 28 adult CI users. Each subject was tested on all 10 CNC word lists. Data were analyzed in terms of lexical characteristics, lexical frequency, neighborhood density, bi-, and tri-phonemic probabilities. To determine whether individual performance variability across lists can be reduced, the standard set of 10 phonetically balanced 50-word lists was redistributed into a new set of lists using two sampling strategies: (a) balancing with respect to word lexical frequency or (b) selecting words with equal probability. The mean performance on the CNC lists varied from 53.1% to 62.4% correct. The average difference between the highest and lowest scores within individuals across the lists was 20.9% (from 12% to 28%). Lexical frequency and bi-phonemic probabilities were correlated with word recognition performance. The range of scores was not significantly reduced for all individuals when responses were simulated with 1,000 sets of redistributed lists, using both types of sampling methods. These results indicate that resampling of words does not affect the test retest reliability and diagnostic value of the CNC word test. PMID- 27194154 TI - Toward 20 T magnetic resonance for human brain studies: opportunities for discovery and neuroscience rationale. AB - An initiative to design and build magnetic resonance imaging (MRI) and spectroscopy (MRS) instruments at 14 T and beyond to 20 T has been underway since 2012. This initiative has been supported by 22 interested participants from the USA and Europe, of which 15 are authors of this review. Advances in high temperature superconductor materials, advances in cryocooling engineering, prospects for non-persistent mode stable magnets, and experiences gained from large-bore, high-field magnet engineering for the nuclear fusion endeavors support the feasibility of a human brain MRI and MRS system with 1 ppm homogeneity over at least a 16-cm diameter volume and a bore size of 68 cm. Twelve neuroscience opportunities are presented as well as an analysis of the biophysical and physiological effects to be investigated before exposing human subjects to the high fields of 14 T and beyond. PMID- 27194157 TI - Activation of MEK/ERK Signaling by PACAP in Guinea Pig Cardiac Neurons. AB - Pituitary adenylate cyclase-activating polypeptide (PACAP) signaling can increase guinea pig cardiac neuron excitability in part through extracellular signal regulated kinase (ERK) activation. The present study examined the PACAP receptors and signaling cascades that stimulate guinea pig cardiac neuron ERK signaling using confocal microscopy to quantify PACAP-induced neuronal phosphorylated ERK (pERK) immunoreactivity. PACAP and maxadilan, but not vasoactive intestinal polypeptide (VIP), increased cardiac neuron pERK, implicating primary roles for PACAP-selective PAC1 receptor (Adcyap1r1) signaling rather than VPAC receptors (Vipr1 and Vipr2) in the generation of cardiac neuron pERK. The adenylyl cyclase (AC) activator forskolin, but not the protein kinase C (PKC) activator phorbol myristate acetate (PMA), increased pERK. Also, Bim1 did not blunt PACAP activation of pERK. Together, the results suggest PAC1 receptor signal transduction via Gs/adenylyl cyclase (AC)/cAMP rather than Gq/phospholipase C (PLC) generated neuronal pERK. Activator and inhibitor studies suggested that the PACAP-mediated pERK activation was PKA-dependent rather than an exchange protein directly activated by a cAMP (EPAC), PKA-independent mechanism. The PACAP-induced pERK was inhibited by the clathrin inhibitor Pitstop2 to block receptor internalization and endosomal signaling. We propose that the PACAP-mediated MEK/ERK activation in cardiac neurons involves both AC/cAMP/PKA signaling and PAC1 receptor internalization/activation of signaling endosomes. PMID- 27194158 TI - Survey study suggests that reverse total shoulder arthroplasty is becoming the treatment of choice for four-part fractures of the humeral head in the elderly. AB - PURPOSE: The role of reverse total shoulder arthroplasty (RTSA) for three and four-part proximal humerus fractures is evolving. However, there does not appear to be a clear consensus amongst surgeons. The purpose of this study is to further define the standard of care, assessing surgeon preference and treatment considerations for management of such fractures. METHODS: Orthopaedic surgeons were surveyed on their training, practice setting, and experience regarding management of four-part proximal humerus fractures. The survey also presented five representative cases to assess treatment preferences. RESULTS: Two hundred five surgeons responded to the survey with fellowship training in shoulder and elbow surgery (114), orthopaedic trauma (35) or sports medicine/other training (56). There was no difference between respondents with years in practice and confidence with performing RTSA, however, surgeons in the academic setting were more confident in performing the surgery. Surgeons preferred RTSA for management of four-part fractures in patients over age 65. However, they also trended to favour hemiarthroplasty with higher co-morbidities. Physicians with more than 11 years of experience were more likely to choose hemiarthroplasty for older and high comorbidity patients. RTSA was not the preferred treatment method for younger, active patients. Patient age and fracture pattern had a greater influence on the surgeon's decision. CONCLUSIONS: There is a consensus in our study population that RTSA is the preferred treatment for four-part proximal humerus fractures for elderly patients with patient age and fracture pattern being the most important factors in making management decisions. LEVEL OF EVIDENCE: Level III - Case controlled study. PMID- 27194159 TI - Surgical treatment for osteoporotic thoracolumbar vertebral collapse using vertebroplasty with posterior spinal fusion: a prospective multicenter study. AB - PURPOSE: The study aimed to investigate the clinical outcomes and limitations after vertebroplasty with posterior spinal fusion (VP+PSF) without neural decompression for osteoporotic vertebral collapse. METHODS: We conducted a prospective multicenter study including 45 patients (12 men and 33 women, mean age: 77.0 years) evaluated between 2008 and 2012. Operation time, blood loss, visual analog scale (VAS) of back pain, neurological status, kyphosis angle in the fused area, and vertebral union of the collapsed vertebra were evaluated. RESULTS: The mean operation time was 162 min and blood loss was 381 mL. The postoperative VAS score significantly improved, and the neurological status improved in 35 patients (83 %), and none of the remaining patients demonstrated a deteriorating neurological status at two years post-operatively. The mean kyphosis angle pre-operatively, immediately post-operatively, and two years post operatively was 23.8 degrees , 10.7 degrees , and 24.3 degrees , respectively, and there was no significant difference between the angles pre-operatively and two years post-operatively. The extensive correction of kyphosis >16 degrees was a risk factor for a higher correction loss and subsequent fracture. Union of the collapsed vertebra was observed in 43 patients (95 %) at two years post operatively. CONCLUSIONS: The present study suggests that spinal stabilization rather than neural decompression is essential to treat OVC. Short-segment VP+PSF can achieve a high union rate of collapsed vertebra and provide a significant improvement in back pain or neurological status with less invasive surgery, but has a limit of kyphosis correction more than 16 degrees . PMID- 27194161 TI - Critical Role of Cx40 in Reduced Endothelial Electrical Coupling by Lipopolysaccharide and Hypoxia-Reoxygenation. AB - BACKGROUND: We discovered that lipopolysaccharide (LPS, an initiating factor in sepsis) and hypoxia-reoxygenation (H/R, a confounding factor) reduce electrical coupling between microvascular endothelial cells from wild-type (WT) but not Cx40 /- mice. Because Cx40 knockout could result in nonspecific effects, this discovery may not establish the causal relationship between Cx40 and reduced coupling. Using the same cell culture model, we aimed to address this uncertainty by using the rescue-of-function approach. METHODS/RESULTS: Electrical coupling between endothelial cells (hind-limb muscle origin) was determined by electrophysiology. LPS, H/R and concurrent LPS + H/R reduced coupling between WT but not Cx40-/- cells. The defect in Cx40-/- cells was rescued by ectopic expression of Cx40, after infecting the cells with adenovirus encoding Cx40. Cx40 /- cells were also engineered to express mutant Cx40 that lacked the carboxyl terminal domain beginning at residue 236 (Cx40x0394;237-358) or 344 (Cx40x0394;345-358). No response to inflammatory stimuli was observed in cells expressing either of these 2 mutants. CONCLUSION: Our data establish the causal relationship between Cx40 and reduced coupling and suggest that the 345-358 amino acid motif of the Cx40 carboxyl terminal is required for reduced coupling. Cx40 may participate in compromised conducted response in the microvasculature during sepsis. PMID- 27194162 TI - PEM or MBI? PMID- 27194160 TI - A vast majority of preliminary reports published in the shoulder literature are not followed by long-time follow-up studies - a literature review. AB - INTRODUCTION: The aim of paper is to check how many preliminary reports (PR) reach a long-term publication (LT), and analyse differences in outcomes and complications between them. METHODS: A literature search was performed to identify shoulder preliminary or early reports. Fifty one papers fulfilled criteria and were categorized for paper topic. Bibliographic searches were undertaken to find LT on the topic from the same author or research group. Outcomes and complications reported in PR were recorded and compared to those reported in LT. RESULTS: Ten out of 51 PR (19.61 %) were followed by a LT with minimum follow-up of five years, by the same authors. Complication and reintervention rate were higher in the LT compared to PR (p < 0.05). Results published on PR were better than results published on LT even though these differences did not reach significance (p = 0.08). DISCUSSION: PR may represent the fastest way to spread new findings. However, concerns regarding short-term follow-up, small sample size bias and decrease in outcomes over time can discourage promising preliminary results. CONCLUSIONS: The vast majority of preliminary reports never reached a LT follow-up paper. Preliminary reports underestimate complications and tend to overestimate outcomes. PMID- 27194163 TI - Do evoked potentials contribute to the functional follow-up and clinical prognosis of multiple sclerosis? AB - The clinical variability and complexity of multiple sclerosis (MS) challenges the individual clinical course prognostication. This study aimed to find out whether multimodal evoked potentials (EP) correlate with the motor components of multiple sclerosis functional composite (MSFCm) and predict clinically relevant motor functional deterioration. One hundred MS patients were assessed at baseline (T 0) and about 7.5 years later (T 1), with visual, somatosensory and motor EP and rated on the Expanded Disability Status Scale (EDSS) and the MSFCm, including the 9 Hole Peg Test and the Timed 25 Foot Walk (T25FW). The Spearman correlation coefficient (r S) was used to evaluate the cross-sectional and longitudinal relationship between EP Z scores and clinical findings. The predictive value of baseline electrophysiological data for clinical worsening (EDSS, 9-HPT, T25FW, MSFCm) during follow-up was assessed by logistic regression analysis. Unlike longitudinal correlations, cross-sectional correlations between EP Z scores and clinical outcomes were all significant and ranged between 0.22 and 0.67 (p < 0.05). The global EP Z score was systematically predictive of EDSS and MSFCm worsening over time (all p < 0.05). EP latency was a better predictor than amplitude, although weaker than latency and amplitude aggregation in the global EP Z score. The study demonstrates that EP numerical scores can be used for motor function monitoring and outcome prediction in patients with MS. PMID- 27194164 TI - Effect of enhanced UV-B radiation on methane emission in a paddy field and rice root exudation of low-molecular-weight organic acids. AB - A local rice variety, "Baijiaolaojing", was grown in a paddy field in the Yuanyang rice terraces under ambient and supplemental levels of ultraviolet-B (UV B, 280-315 nm) radiation. The effects of enhanced UV-B radiation (5 and 10 kJ m( 2) d(-1)) on methane emissions in the paddy field were evaluated using a closed chamber gas chromatography-based system, and the contents of low-molecular-weight organic acids (LMWOAs) in root exudates were determined by high-performance liquid chromatography (HPLC). Peaks in methane emissions in the paddy field were detected at 60, 80 and 100 days after rice transplantation. The highest level of cumulative methane emissions occurred at the tillering stage, followed by the jointing-booting and maturity stages. The lowest level was found at the flowering stage. The enhanced UV-B radiation did not change the seasonal variation in methane emissions in the paddy field; however, it induced a significant increase in the flux of methane emissions at the jointing-booting and maturity stages, as well as a significant increase in the cumulative flux of methane emissions throughout the growth period. In addition, the enhanced UV-B radiation caused an increase in the contents of oxalic acid and succinic acid and a decrease in the contents of tartaric acid and malic acid in rice root exudates. Furthermore, a significant positive correlation (r = 0.725, p < 0.01) was found between the content of oxalic acid and the methane emissions in the paddy field. The results indicated that enhanced UV-B radiation promoted methane emissions in the paddy field, which was closely associated with its impact on the exudation of LMWOAs by rice roots. PMID- 27194165 TI - Lipid-based drug delivery systems in the treatment of wet age-related macular degeneration. AB - Recent advances in drug delivery technology have amplified potential opportunities to treat the debilitating diseases that affect the posterior segment of the eye in a less invasive and more efficient manner. Current methods for effective drug delivery to the back of the eye are hindered by many barriers and limitations. As a consequence, considerable efforts have been directed towards developing new materials to selectively deliver drug directly to the target site. This review focuses on lipid-based delivery systems which show promise in improving treatment for the most common disease of the posterior segment of the eye in the developed world, age-related macular degeneration, with an emphasis upon on-demand delivery systems as they have greater potential to overcome the current limitations. PMID- 27194166 TI - The Pharmacological Management of Complex Regional Pain Syndrome in Pediatric Patients. AB - The awareness of complex regional pain syndrome (CRPS) in the pediatric population is increasing. The condition involves regional pain that is out of proportion to any initiating event (if there is one) and is associated with sensory, functional, autonomic, and inflammatory changes in the region of the pain. The signs and symptoms of CRPS can vary between patients and stage of the disease process. Like many chronic pain conditions, it is often associated with significant disability and a detrimental effect on quality of life. It has a complex pathophysiology that remains poorly understood but provides many potential targets for treatments. Management involves a biopsychosocial formulation that encompasses physical and psychological interventions alongside pharmacological strategies. We review the current evidence for the treatment of this condition in children, with particular reference to pharmacological management. PMID- 27194167 TI - The Diathesis-Epilepsy Model: How Past Events Impact the Development of Epilepsy and Comorbidities. AB - In epilepsy, seizures and comorbidities (e.g., cognitive deficits and depression) occur when specific thresholds are crossed. These thresholds depend on the diathesis (or vulnerability) of a given individual. The diathesis is controlled by multiple genetic and environmental factors. Diathesis changes over multiple timescales: on a daily basis, and as part of the development/aging processes, etc. The diathesis-epilepsy model introduced here provides a conceptual framework to understand how past events (e.g., a very stressful event) can directly influence the occurrence of epilepsy and comorbidities later in life. Experimental evidence supports this model, and the existence of biomarkers predictive of a vulnerability state have led to the development of preventive therapeutic strategies. Epigenetic modifications could be a key determinant of diathesis. Their role is discussed. PMID- 27194169 TI - Coexistence of acromegaly with dural arteriovenous fistula of the cavernous sinus. PMID- 27194168 TI - The Role of MDM2 Amplification and Overexpression in Tumorigenesis. AB - Mouse double minute 2 (MDM2) is a critical negative regulator of the tumor suppressor p53, playing a key role in controlling its transcriptional activity, protein stability, and nuclear localization. MDM2 expression is up-regulated in numerous cancers, resulting in a loss of p53-dependent activities, such as apoptosis and cell-cycle arrest. Genetic amplification and inheritance of MDM2 promoter single-nucleotide polymorphisms (SNPs) are the two best-studied mechanisms for up-regulating MDM2 activity. This article provides an overview of these events in human cancer, highlighting the frequent occurrence of MDM2 amplification in sarcoma and the role of SNP309 and SNP285 in regulating MDM2 expression and cancer risk. The availability of large-scale genomic profiling datasets, like those from The Cancer Genome Atlas Research Network, have provided the opportunity to evaluate the consequences of MDM2 amplification and SNP inheritance across high-quality tumor samples from diverse cancer indications. PMID- 27194170 TI - Cervical spinal canal narrowing in idiopathic syringomyelia. AB - INTRODUCTION: The cervical spine in Chiari I patient with syringomyelia has significantly different anteroposterior diameters than it does in Chiari I patients without syringomyelia. We tested the hypothesis that patients with idiopathic syringomyelia (IS) also have abnormal cervical spinal canal diameters. The finding in both groups may relate to the pathogenesis of syringomyelia. METHODS: Local institutional review boards approved this retrospective study. Patients with IS were compared to age-matched controls with normal sagittal spine MR. All subjects had T1-weighted spin-echo (500/20) and T2-weighted fast spin echo (2000/90) sagittal cervical spine images at 1.5 T. Readers blinded to demographic data and study hypothesis measured anteroposterior diameters at each cervical level. The spinal canal diameters were compared with a Mann-Whitney U test. The overall difference was assessed with a Friedman test. Seventeen subjects were read by two reviewers to assess inter-rater reliability. RESULTS: Fifty IS patients with 50 age-matched controls were studied. IS subjects had one or more syrinxes varying from 1 to 19 spinal segments. Spinal canal diameters narrowed from C1 to C3 and then enlarged from C5 to C7 in both groups. Diameters from C2 to C4 were narrower in the IS group (p < 0.005) than in controls. The ratio of the C3 to the C7 diameters was also smaller (p = 0.004) in IS than controls. Collectively, the spinal canal diameters in the IS were significantly different from controls (Friedman test p < 0.0001). CONCLUSION: Patients with IS have abnormally narrow upper and mid cervical spinal canal diameters and greater positive tapering between C3 and C7. PMID- 27194171 TI - Personalized medicine for diabetes: a special issue. PMID- 27194172 TI - Innovative strategies to improve diabetes outcomes in disadvantaged populations. AB - Diabetes disproportionately affects disadvantaged populations. Eighty percent of deaths directly caused by diabetes occurred in low- and middle-income countries. In high-income countries, there are marked disparities in diabetes control among racial/ethnic minorities and those with low socio-economic status. Innovative, effective and cost-effective strategies are needed to improve diabetes outcomes in these populations. Technological advances, peer educators and community health workers have expanded methodologies to reach, educate and monitor individuals with diabetes. In the present manuscript we review the outcomes of these strategies, and describe the barriers to and facilitators of these approaches for improving diabetes outcomes. PMID- 27194174 TI - Delivery of Type 2 diabetes care in low- and middle-income countries: lessons from Lima, Peru. AB - AIMS: The health system's response is crucial to addressing the increasing burden of diabetes, particularly that affecting low- and middle-income countries. This study aims to assess the facilitators and barriers that help or hinder access to care for people with diabetes in Peru. METHODS: We used a survey tool to design and collect qualitative and quantitative data from primary and secondary sources of information at different levels of the health system. We performed 111 interviews in Lima, the capital city of Peru, with patients with diabetes, healthcare providers and healthcare officials. We applied the six building blocks framework proposed by the World Health Organization in our analysis. RESULTS: We found low political commitment, as well as several barriers that directly affect access to medicines, regular laboratory check-ups and follow-up appointments for diabetes, especially at the primary healthcare level. Three major system-level barriers were identified: (1) the availability of information at different healthcare system levels that affects several processes in the healthcare provision; (2) insufficient financial resources; and (3) insufficient human resources trained in diabetes management. CONCLUSION: Despite an initial political commitment by the Peruvian government to improve the delivery of diabetes care, there exist several key limitations that affect access to adequate diabetes care, especially at the primary healthcare level. In a context in which various low- and middle-income countries are aiming to achieve universal health coverage, this study provides lessons for the implementation of strategies related to diabetes care delivery. PMID- 27194173 TI - Outpatient diabetes clinical decision support: current status and future directions. AB - Outpatient clinical decision support systems have had an inconsistent impact on key aspects of diabetes care. A principal barrier to success has been low use rates in many settings. Here, we identify key aspects of clinical decision support system design, content and implementation that are related to sustained high use rates and positive impacts on glucose, blood pressure and lipid management. Current diabetes clinical decision support systems may be improved by prioritizing care recommendations, improving communication of treatment-relevant information to patients, using such systems for care coordination and case management and integrating patient-reported information and data from remote devices into clinical decision algorithms and interfaces. PMID- 27194175 TI - A prospective randomized controlled study of a virtual clinic integrating primary and specialist care for patients with Type 2 diabetes mellitus. AB - AIMS: To investigate the effectiveness of a diabetes virtual clinic to enhance diabetes in primary care by developing clinical management plans for patients with suboptimal metabolic control and/or case complexity. METHODS: A prospective study with randomized allocation to virtual clinic or usual care. Patients with Type 2 diabetes (n = 208) were recruited from six general practices in South London. The primary outcome for the study was glycaemic control, secondary outcomes included: lipids, blood pressure, weight (kg and BMI) and renal function (eGFR). Data were collected from participants' records at baseline and 12 months. We also considered process measures including therapy optimization. RESULTS: The 12-month data show equivalence between the virtual clinic and control groups for glycaemic control with both achieving clinically significant reductions in HbA1c of 8 mmol/mol (0.6 +/- 1.7%) and 10 mmol/mol (0.8 +/- 1.9%), respectively (P = 0.4). The virtual clinic group showed superiority over the intervention group for blood pressure control with a mean reduction in systolic blood pressure of 6 +/- 16 mmHg compared with an increased of 2 +/- 18 mmHg in the control group (P = 0.008). There were no significant differences between the groups in terms of cholesterol, weight and renal function. Process measures showed an increased level of therapy adjustment in the virtual clinic group. CONCLUSION: The virtual clinic model explored in this study showed a clinically important improvement in glycaemic control. Although this improvement was not superior to that observed in the control participants, this might be attributable to the systemic impact of the virtual clinic on the practice as a whole. PMID- 27194177 TI - Ridge preservation of extraction sockets with chronic pathology using Bio-Oss(r) Collagen with or without collagen membrane: an experimental study in dogs. AB - OBJECTIVES: This study aimed to evaluate the dynamics of newly bone formation and dimensional change in diseased extraction sockets using Bio-Oss(r) Collagen with or without a collagen membrane. MATERIAL AND METHODS: In six beagle dogs, right and left 3rd and 4th mandibular premolars were hemisected and the distal roots were removed. Combined endodontic-periodontic lesions were induced in all sites using black silk, collagen sponge, endodontic files, and application of Porphyromonas gingivalis. After 4 months, among 4 premolars, three teeth were randomly selected per dog and allocated to the following experimental groups: Control group (no treatment but debridement), Test 1 group (only Bio-Oss(r) Collagen graft), and Test 2 group (Bio-Oss(r) Collagen graft with a collagen membrane). After 7 months from the baseline, the beagle dogs were sacrificed for histomorphometric and Micro-CT analysis. RESULTS: The vertical distance between buccal and lingual crests in the Control group (2.22 +/- 0.26 mm) and Test 2 group (1.80 +/- 0.16 mm) was significantly different. The socket of the Test 2 group (27.04 +/- 5.25%) was occupied by a greater quantity of bone graft compared to the Test 1 group (18.49 +/- 2.11%). CONCLUSION: Ridge preservation in diseased extraction sockets could compensate for buccal bone resorption by contact osteogenesis surrounding the bone graft particles at the bucco-coronal area during socket healing, and the application of a collagen membrane at the entrance of the socket is useful for preserving graft material at the coronal part of the socket. PMID- 27194176 TI - Preoperative chemoradiation with paclitaxel-carboplatin or with fluorouracil oxaliplatin-folinic acid (FOLFOX) for resectable esophageal and junctional cancer: the PROTECT-1402, randomized phase 2 trial. AB - BACKGROUND: Often curative treatment for locally advanced resectable esophageal or gastro-esophageal junctional cancer consists of concurrent neoadjuvant radiotherapy and chemotherapy followed by surgery. Currently, one of the most commonly used chemotherapy regimens in this setting is a combination of a fluoropyrimidin and of a platinum analogue. Due to the promising results of the recent CROSS trial, another regimen combining paclitaxel and carboplatin is also widely used by European and American centers. No clinical study has shown the superiority of one treatment over the other. The objective of this Phase II study is to clarify clinical practice by comparing these two chemotherapy treatments. Our aim is to evaluate, in operable esophageal and gastro-esophageal junctional cancer, the complete resection rate and severe postoperative morbidity rate associated with these two neoadjuvant chemotherapeutic regimens (carboplatin paclitaxel or fluorouracil-oxaliplatin-folinic acid) when each is combined with the radiation regime utilized in the CROSS trial. METHODS/DESIGN: PROTECT is a prospective, randomized, multicenter, open arms, phase II trial. Eligible patients will have a histologically confirmed adenocarcinoma or squamous cell carcinoma and be treated with neoadjuvant radiochemotherapy followed by surgery for stage IIB or stage III resectable esophageal cancer. A total of 106 patients will be randomized to receive either 3 cycles of FOLFOX combined to concurrent radiotherapy (41.4 Grays) or carboplatin and paclitaxel with the same radiation regimen, using a 1:1 allocation ratio. DISCUSSION: This ongoing trial offers the unique opportunity to compare two standards of chemotherapy delivered with a common regimen of preoperative radiation, in the setting of operable locally advanced esophageal or gastro-esophageal junctional tumors. TRIAL REGISTRATION: NCT02359968 (ClinicalTrials.gov) (registration date: 9 FEB 2015), EudraCT: 2014 000649-62 (registration date: 10 FEB 2014). PMID- 27194179 TI - Criteria for CT and Initial Management of Head Injured Infants: A Review. AB - Criteria for computed tomography (CT) to head injured infants have not been established. Since the identification of neurological findings is difficult in infants, examination by CT may be necessary in some cases, but it may be difficult to perform CT because of problems with radiation exposure and body movement. Moreover, even though no intracranial abnormality was found immediately after injury, abnormal findings may appear after several hours. From this viewpoint, course observation after injury may be more important than CT in the initial treatment of head trauma in infants. The complaints and neurological manifestations of infants, particularly those aged 2 or younger, are frequently unclear; therefore, there is an opinion that CT is recommended for all pediatric patients. However, the appropriateness of its use should be determined after confirming the mechanism of injury, consciousness level, neurological findings, and presence/absence of a history of abuse. Among the currently available rules specifying criteria for CT of infants with head trauma, the Pediatric Emergency Care Applied Research Network (PECARN) study may be regarded as reliable at present. In Japan, where the majority of emergency hospitals are using CT, it may be necessary to develop criteria for CT in consideration of the actual situation. CT diagnosis for pediatric head trauma is not always necessary. When no imaging is performed, this should be fully explained at the initial treatment before selecting course observation at home. Checking on a state of the patients by telephone is useful for both patients and physicians. PMID- 27194178 TI - Ultrasound-guided Femoral Artery Access for Minimally Invasive Neuro-intervention and Risk Factors for Access Site Hematoma. AB - Although ultrasound (US) guidance for venous access is becoming the "standard of care" for preventing access site complications, its feasibility for arterial access has not been fully investigated, especially in the neuro-interventional population. We conducted the first prospective cohort study on US-guided femoral artery access during neuro-interventional procedure. This study included 64 consecutive patients who underwent US-guided femoral artery access through 66 arterial access sites for diagnostic and/or neuro-interventional purposes. The number of attempts required for both the sheath insertion and the success of anterior wall puncture were recorded. In addition, the occurrence of major complications and hematoma formation on the arterial access site examined by US were statistically analyzed. The median number of attempts was 1 (1-2) and first pass success rate was 63.6%. Anterior wall puncture was achieved in 98.5%. In one case (1.5%), a pseudoaneurysm was observed. In all cases, US clearly depicted a common femoral artery (CFA) and its bifurcation. Post-procedural hematoma was detected in 13 cases (19.7%), most of which were "tiny" or "moderate" in size. Low body mass index and antiplatelet therapy were the independent risk factors for access site hematoma. The US-guided CFA access was feasible even in neuro interventional procedure. The method was particularly helpful in the patients with un-palpable pulsation of femoral arteries. To prevent arterial access site hematoma, special care should be taken in patients with low body mass index and who are on antiplatelet therapy. PMID- 27194180 TI - Correlative nonlinear optical microscopy and infrared nanoscopy reveals collagen degradation in altered parchments. AB - This paper presents the correlative imaging of collagen denaturation by nonlinear optical microscopy (NLO) and nanoscale infrared (IR) spectroscopy to obtain morphological and chemical information at different length scales. Such multiscale correlated measurements are applied to the investigation of ancient parchments, which are mainly composed of dermal fibrillar collagen. The main issue is to characterize gelatinization, the ultimate and irreversible alteration corresponding to collagen denaturation to gelatin, which may also occur in biological tissues. Key information about collagen and gelatin signatures is obtained in parchments and assessed by characterizing the denaturation of pure collagen reference samples. A new absorbing band is observed near the amide I band in the IR spectra, correlated to the onset of fluorescence signals in NLO images. Meanwhile, a strong decrease is observed in Second Harmonic signals, which are a structural probe of the fibrillar organization of the collagen at the micrometer scale. NLO microscopy therefore appears as a powerful tool to reveal collagen degradation in a non-invasive way. It should provide a relevant method to assess or monitor the condition of collagen-based materials in museum and archival collections and opens avenues for a broad range of applications regarding this widespread biological material. PMID- 27194181 TI - Oxidation-Based Continuous Laser Writing in Vertical Nano-Crystalline Graphite Thin Films. AB - Nano and femtosecond laser writing are becoming very popular techniques for patterning carbon-based materials, as they are single-step processes enabling the drawing of complex shapes without photoresist. However, pulsed laser writing requires costly laser sources and is known to cause damages to the surrounding material. By comparison, continuous-wave lasers are cheap, stable and provide energy at a more moderate rate. Here, we show that a continuous-wave laser may be used to pattern vertical nano-crystalline graphite thin films with very few macroscale defects. Moreover, a spatially resolved study of the impact of the annealing to the crystalline structure and to the oxygen ingress in the film is provided: amorphization, matter removal and high oxygen content at the center of the beam; sp(2) clustering and low oxygen content at its periphery. These data strongly suggest that amorphization and matter removal are controlled by carbon oxidation. The simultaneous occurrence of oxidation and amorphization results in a unique evolution of the Raman spectra as a function of annealing time, with a decrease of the I(D)/I(G) values but an upshift of the G peak frequency. PMID- 27194182 TI - Fragmentation, Fusion, and Genetic Homogeneity in a Calcareous Sponge (Porifera, Calcarea). AB - Sessile marine invertebrates living on hard substrata usually present strategies such as size variations, longer life spans, fragmentation and fusion to occupy and compete for space. Calcareous sponges are usually small and short-lived, and some species are known to undergo frequent fragmentation and fusion events. However, whether fusion occurs only between genetically identical individuals remains unclear. We investigated the occurrence of chimaeras in the calcareous sponge Clathrina aurea by following the dynamics of fragmentation and fusion of 66 individuals in the field for up to 18 months and determined size variations and the life span of each individual. Microsatellites were used to determine whether fusion events occur among genetically different individuals. Growth and shrinkage of individuals were frequently observed, showing that size cannot be associated with age in C. aurea. The life span of the species ranged from 1 to 16 months (mean: 4.7 months). Short life spans and variable growth rates have been observed in other species of the class Calcarea. Fragmentation and fusion events were observed, but fusion events always occurred between genetically identical individuals, as has been suggested by graft experiments in adult Demospongiae and other Calcarea. These results suggest that at least C. aurea adults may have some mechanism to avoid chimaerism. PMID- 27194189 TI - The relationship between helminth infections and low haemoglobin levels in Ethiopian children with blood type A. AB - The current study was conducted to evaluate the nature of association of ABO blood type with helminth infection and related reduction in haemoglobin concentration. Stool samples were collected from 403 school-age children attending Tikur Wuha Elementary School from February to April 2011. Helminth infection was examined using formol-ether concentration and thick Kato-Katz (two slides per stool specimen) techniques. Haemoglobin level was determined using a HemoCue machine and ABO blood type was determined using the antisera haemagglutination test. Nutritional status was assessed using height and weight measurements. Out of 403 children examined, 169, 120, 96 and 18 had blood type O, A, B and AB, respectively. The prevalences of helminth infections were 46.9% for hookworm, 24.6% for Schistosoma mansoni, 4.2% for Ascaris lumbricoides, 1.7% for Trichuris trichiura and 58.3% for any helminth species. The relative odds of infection with at least one helminth species was significantly higher among children with blood type A (adjusted odds ratio (AOR), 2.10; 95% confidence interval (CI), 1.28-3.45) or blood type B (AOR, 2.08; 95% CI, 1.22-3.56) as compared to children with blood type O. Among children infected with helminths, mean haemoglobin concentration was lower in those with blood type A than those with blood type O (beta, -0.36; 95% CI, -0.72 to -0.01). The relative odds of hookworm infection (AOR, 1.78; 95% CI, 1.08-2.92) and related reduction in haemogobin levels (beta, -0.45; 95% CI, -0.84 to -0.04) was higher among children with blood type A as compared to those with blood type O. Although the difference was not significant, the relative odds of S. mansoni or A. lumbricoides infections and related reduction in haemoglobin levels was also higher in children with blood type A or B as compared to children with blood type O. In conclusion, children with blood type A are associated with an increased risk of helminth, particularly hookworm, infection and related reduction in haemoglobin level. The mechanisms by which blood type A makes children susceptible to helminth infection and a related reduction in haemoglobin level ought to be investigated. PMID- 27194190 TI - Gender variability in electromyographic activity, in vivo behaviour of the human gastrocnemius and mechanical capacity during the take-off phase of a countermovement jump. AB - PURPOSE: The purpose of this study was to analyse gender differences in neuromuscular behaviour of the gastrocnemius and vastus lateralis during the take off phase of a countermovement jump (CMJ), using direct measures (ground reaction forces, muscle activity and dynamic ultrasound). METHODS: Sixty-four young adults (aged 18-25 years) participated voluntarily in this study, 35 men and 29 women. The firing of the trigger allowed obtainment of data collection vertical ground reaction forces (GRF), surface electromyography activity (sEMG) and dynamic ultrasound gastrocnemius of both legs. RESULTS: Statistically significant gender differences were observed in the jump performance, which appear to be based on differences in muscle architecture and the electrical activation of the gastrocnemius muscles and vastus lateralis. So while men developed greater peak power, velocity take-offs and jump heights, jump kinetics compared to women, women also required a higher electrical activity to develop lower power values. Additionally, the men had higher values pennation angles and muscle thickness than women. CONCLUSION: Men show higher performance of the jump test than women, due to significant statistical differences in the values of muscle architecture (pennation angle and thickness muscle), lower Neural Efficiency Index and a higher amount of sEMG activity per second during the take-off phase of a CMJ. PMID- 27194183 TI - Meal patterns across ten European countries - results from the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study. AB - OBJECTIVE: To characterize meal patterns across ten European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study. DESIGN: Cross-sectional study utilizing dietary data collected through a standardized 24 h diet recall during 1995-2000. Eleven predefined intake occasions across a 24 h period were assessed during the interview. In the present descriptive report, meal patterns were analysed in terms of daily number of intake occasions, the proportion reporting each intake occasion and the energy contributions from each intake occasion. SETTING: Twenty seven centres across ten European countries. SUBJECTS: Women (64 %) and men (36 %) aged 35-74 years (n 36 020). RESULTS: Pronounced differences in meal patterns emerged both across centres within the same country and across different countries, with a trend for fewer intake occasions per day in Mediterranean countries compared with central and northern Europe. Differences were also found for daily energy intake provided by lunch, with 38-43 % for women and 41-45 % for men within Mediterranean countries compared with 16-27 % for women and 20-26 % for men in central and northern European countries. Likewise, a south-north gradient was found for daily energy intake from snacks, with 13-20 % (women) and 10-17 % (men) in Mediterranean countries compared with 24-34 % (women) and 23-35 % (men) in central/northern Europe. CONCLUSIONS: We found distinct differences in meal patterns with marked diversity for intake frequency and lunch and snack consumption between Mediterranean and central/northern European countries. Monitoring of meal patterns across various cultures and populations could provide critical context to the research efforts to characterize relationships between dietary intake and health. PMID- 27194191 TI - Old model organisms and new behavioral end-points: Swimming alteration as an ecotoxicological response. AB - Behavioral responses of aquatic organisms have received much less attention than developmental or reproductive ones due to the scarce presence of user-friendly tools for their acquisition. The technological development of data acquisition systems for quantifying behavior in the aquatic environment and the increase of studies on the understanding the relationship between the behavior of aquatic organisms and the physiological/ecological activities have generated renewed interest in using behavioral responses also in marine ecotoxicology. Recent reviews on freshwater environment show that behavioral end-points are comparatively fast and sensitive, and warrant further attention as tools for assessing the toxicological effects of environmental contaminants. In this mini review, we perform a systematic analysis of the most recent works that have used marine invertebrate swimming alteration as behavioral end-point in ecotoxicological studies by assessing the differences between behavioral and acute responses in a wide range of species, in order to compare their sensitivity. PMID- 27194192 TI - Letter to the Editor: The Prescription Opioid Epidemic in Developed Versus Underdeveloped Countries: Is there a Happy Medium? PMID- 27194193 TI - Establishing "abuse-deterrence equivalence" for generic abuse-deterrent opioid formulations: A proposed development framework. AB - Abuse-deterrent formulations are one strategy for mitigating the epidemic of prescription opioid abuse. Regulatory guidance documents describe the requirements for developing abuse-deterrent formulations of novel drugs and formulations; however, they do not address "abuse-deterrence equivalence" for generic formulations. As generics may be produced with different excipients and formulations compared to reference drugs, differences in their properties may impact their abuse-deterrent features. Currently, it is unclear what specific studies are needed to support generic abuse-deterrence claims. This commentary outlines several recommendations on the in vitro and in vivo testing required, including the conditions for conducting a human abuse potential study. PMID- 27194194 TI - The emerging therapeutic roles of kappa-opioid agonists. AB - The current practice of MU-opioid receptor agonists such as morphine as the primary means of acute and chronic pain relief has several dangerous consequences that limit their effectiveness, including respiratory depression, gastrointestinal motility inhibition, addiction, tolerance, and abuse. Several other opioid receptors, notably the MU-opioid (KOP) receptor, have long been known to play a role in pain relief. Recent discoveries and advancements in laboratory techniques have allowed significant developments of KOP agonists as potential novel therapies for pain relief and other pathological processes. These drugs exhibit none of the classic opioid adverse effects and have displayed pronounced analgesia in several different scenarios. New formulations since 2014 have unveiled increased oral bioavailability, exceptional peripheral versus central selectivity, and a positive safety profile. Continued refinements of established MU-opioid agonist formulations have virtually eliminated the centrally mediated side effects of dysphoria and sedation that limited the applicability of previous KOP agonists. Further research is required to better elucidate the potential of these compounds in pain management, as well as in the mediation or modulation of other complex pathophysiological processes as therapeutic agents. PMID- 27194195 TI - State-level and system-level opioid prescribing policies: The impact on provider practices and overdose deaths, a systematic review. AB - OBJECTIVE: In response to persistent public health concerns regarding prescription opioids, many states and healthcare systems have implemented legislation and policies intended to regulate or guide opioid prescribing. The overall impact of these policies is still uncertain. The aim of this systematic review was to examine the existing evidence of provider-level and patient-level outcomes preimplementation and postimplementation of policies and legislation constructed to impact provider prescribing practices around opioid analgesics. DESIGN: A systematic search of MEDLINE, EMBASE, the Web of Science, and the Cochrane Database of Systematic Reviews was conducted to identify studies evaluating the impact of opioid prescribing policies on provider-level and patient-level outcomes. The systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Eleven studies were included in the review. A meta-analysis was not possible due to between-study heterogeneity. Six of the studies assessed state level policies, and five were at the level of the healthcare system or hospital. Studies showed temporal associations between policy implementation and reductions in opioid prescribing, as well as opioid-related overdoses. Results were mixed regarding the impact of policies on misuse. The majority of the studies were judged to be of low quality based on the GRADE criteria. CONCLUSIONS: There is low to moderate quality evidence suggesting that the presence of opioid prescribing policy will reduce the amount and strength of opioid prescribed. The presence of these policies may impact the number of overdoses, but there is no clear evidence to suggest that it reduces opioid misuse. PMID- 27194197 TI - Methadone conversion in infants and children: Retrospective cohort study of 199 pediatric inpatients. AB - OBJECTIVE: Methadone administration has increased in pediatric clinical settings. This review is an attempt to ascertain an equianalgesic dose ratio for methadone in the pediatric population using standard adult dose conversion guidelines. SETTING: US tertiary children's hospital. PATIENTS: Hospitalized pediatric patients, 0-18 years of age. MAIN OUTCOME MEASURES: A retrospective chart review was conducted for patients who were converted from their initial opioid therapy regimen (morphine, hydromorphone, and/or fentanyl) to methadone. The primary endpoint was whether or not a dose correction was needed for methadone in the 6 days following conversion using standard dose conversion charts for adults. Documented clinical signs of withdrawal, unrelieved pain, or oversedation were examined. RESULTS: The majority (53.7 percent) of the 199 children were converted to methadone on intensive care units prior extubation or postextubation. The mean conversion ratio was 23.7 mg of oral morphine to 1 mg of oral methadone (median, 18.8 mg:1 mg, SD=25.7). Most patients experienced an adequate conversion (n=115, 57.8 percent), while 83 (41.7 percent) appeared undermedicated, and one child was oversedated. There were no associations found with conversion ratios for initial morphine dose, days to conversion, or effect of withdrawal of concomitant agents with potential for withdrawal. CONCLUSIONS: Opioid conversion to methadone is commonly practiced at our institution; however, dosing was significantly lower compared to adult conversion ratios, and more than 40 percent of children were undermedicated. The majority of children in this study received opioids for sedation while intubated and ventilated; therefore, safe and efficacious pediatric methadone conversion rates remain unclear. Prospective studies are needed. PMID- 27194196 TI - Analgesic utilization before and after rescheduling of hydrocodone in a large academic level 1 trauma center. AB - BACKGROUND: Hydrocodone-containing products were recently rescheduled from Drug Enforcement Agency (DEA) schedule III to schedule II due to concerns of abuse and misuse. These changes went into effect on October 6, 2014. OBJECTIVE: This quality improvement project involved a retrospective analysis to determine the effect of the DEA schedule change on prescribing habits of hydrocodone-containing products as well as the remaining schedule III and IV opioids, codeine (schedule III) and tramadol (schedule IV). METHODS: The authors performed a medication use evaluation at our academic level 1 trauma hospital system on outpatient use of hydrocodone-containing products, tramadol, and codeine-containing products for 6 months before and 6 months after the change to schedule II using our electronic record and pharmacy system. RESULTS: A total of 88,428 prescription orders were analyzed. Comparison of prescriptions before and after the DEA schedule changes showed hydrocodone prescriptions reduced from an average of 225.97 per day to 1.20 per day. In addition, tramadol increased from 60.04 per day to 91.85 per day and codeine from 6.81 per day to 98.94 per day. CONCLUSIONS: Our data show a very substantial decrease in utilization of hydrocodone-containing products and concomitant increase in the utilization of tramadol and codeine products at our hospital after the DEA schedule change. PMID- 27194199 TI - Six-month, open-label study of hydrocodone extended release formulated with abuse deterrence technology: Safety, maintenance of analgesia, and abuse potential. AB - OBJECTIVE: To evaluate long-term safety, maintenance of analgesia, and aberrant drug-related behaviors of hydrocodone extended release (ER) formulated with CIMA(r) Abuse-Deterrence Technology. DESIGN: Phase 3, multicenter, open-label extension. SETTING: Fifty-six US centers. PATIENTS: Adults with chronic low back pain completing a 12-week placebocontrolled study of abuse-deterrent hydrocodone ER were eligible. One hundred eighty-two patients enrolled and received >=1 dose of study drug, 170 entered openlabel treatment, and 136 completed the study. INTERVENTIONS: Patients receiving hydrocodone ER in the 12-week, placebo controlled study continued their previous dose unless adjustment was needed; those previously receiving placebo (n=78) underwent dose titration/adjustment to an analgesic dose (15-90 mg every 12 hours). Patients received 22 weeks of open label treatment. MAIN OUTCOME MEASURES: SAFETY: adverse events (AEs). Maintenance of analgesia: worst pain intensity (WPI) and average pain intensity (API) at each study visit. Aberrant drug behavior: study drug loss and diversion. RESULTS: AEs were reported for 65/182 (36 percent) patients during dose titration/ adjustment and 88/170 (52 percent) during open-label treatment. No treatmentrelated serious AEs were reported. There were no clinically meaningful trends in other safety assessments, including physical examinations and pure tone audiometry. One patient receiving hydrocodone ER 30 mg twice daily experienced a severe AE of neurosensory deafness that was considered treatment related. Mean WPI and API remained steady throughout open-label treatment. Six (3 percent) patients reported medication loss, and 5 (3 percent) reported diversion. CONCLUSIONS: Abuse-deterrent hydrocodone ER was generally well tolerated in patients with chronic low back pain, maintained efficacy, and was associated with low rates of loss and diversion. PMID- 27194198 TI - Methadone prolongs cardiac conduction in young patients with cancer-related pain. AB - OBJECTIVE: Methadone prolongs cardiac conduction, from mild corrected QT (QTc) prolongation to torsades de pointes and ventricular fibrillation, in adults. However, methadone use for pain and its effects on cardiac conduction have not been investigated in pediatric populations. METHODS: A retrospective review of QTc intervals in patients receiving methadone analgesia was conducted. Medical records from a 4-year period (September 2006 to October 2010) at a pediatric oncology institution were reviewed, and correlations were tested between cardiac conduction and methadone dosage and duration of therapy, electrolyte levels, renal and hepatic dysfunction, and concurrent medications. RESULTS: Of the 61 patients who received methadone, 37 met our inclusion criteria and underwent 137 electrocardiograms (ECGs). During methadone treatment, the mean QTc was longer than that at baseline (446.5 vs 437.55 ms). The mean methadone dose was 27.0+/ 24.3 mg/d (range, 5-125 mg/d; median, 20 mg/d) or 0.47+/-0.45 mg/kg per day (range, 0.05-2.25 mg/kg per day; median, 0.37 mg/kg per day), and the mean duration of therapy was 49 days. The authors identified a correlation between automated and manual ECG readings by two cardiologists (Pearson r=0.649; p<0.0001), but the authors found no correlations between methadone dose or duration and concurrent QTc-prolonging medications, sex, age, electrolyte abnormalities, or renal or hepatic dysfunction. CONCLUSION: At a clinically effective analgesic dose, methadone dosage and duration were not correlated with QTc prolongation, even in the presence of other risk factors, suggesting that methadone use may be safe in pediatric populations. The correlation between automated and manual ECG readings suggests that automated ECG readings are reliable for monitoring cardiac conductivity during the reported methadone-dosage regimens. PMID- 27194200 TI - Opioid use following the introduction of an extended-release oxycodone formulation with tamper-resistant properties: Prospective historical chart review in methadone-maintained patients. AB - OBJECTIVE: Emerging data are demonstrating that tamper-resistant opioids may play an important role in changing prescription opioid abuse behaviors. This study was a chart review to examine if the reformulation of OxyContin(r) into a version with tamper-resistant properties (OxyNEO(r)) had an impact on oxycodone-positive urine drug screens (UDSs) in opioid-dependent patients receiving methadone maintenance therapy (MMT). DESIGN: The historical element of this study examined 250 eligible charts from patients on MMT who had data during the time periods when only OxyContin was available (baseline period), during the transition to OxyNEO, and when only OxyNEO was available. The prospective element included an exploratory questionnaire regarding retrospective opioid use. SETTING: The study was conducted at three methadone clinics, in Oshawa, Peterborough, and Scarborough in Ontario, Canada. PARTICIPANTS: Male and female patients were eligible if they had a diagnosis of opioid dependency, received MMT, and had at least one oxycodone-positive UDS during the baseline period. INTERVENTION: This was a noninterventional study. MAIN OUTCOME MEASURE: The main outcome was the number of oxycodonepositive UDSs. RESULTS: The results demonstrated a marked reduction in oxycodone-positive UDSs that showed stepwise, statistically significant decreases during the transition and post-OxyContin periods relative to baseline. While the oxycodone-positive UDS results were decreasing, morphine related-positive UDSs remained relatively stable during the same periods. There were no significant gender differences noted. CONCLUSIONS: The introduction of OxyNEO was associated with a statistically significant reduction in oxycodone exposure in a population of methadone-maintained patients. PMID- 27194201 TI - Use of Osmotic Pumps to Establish the Pharmacokinetic-Pharmacodynamic Relationship and Define Desirable Human Performance Characteristics for Aggrecanase Inhibitors. AB - The development of reliable relationships between in vivo target engagement, pharmacodynamic activity, and efficacy in chronic disease models is beneficial for enabling hypothesis-driven drug discovery and facilitating the development of patient-focused candidate selection criteria. Toward those ends, osmotic infusion pumps can be useful for overcoming limitations in the PK properties of proof-of concept (POC) compounds to accelerate the development of such relationships. In this report, we describe the application of this strategy to the development of hydantoin-derived aggrecanase inhibitors (eg, 3) for the treatment of osteoarthiritis (OA). Potent, selective inhibitors were efficacious in both chemical and surgical models of OA when exposures were sustained in excess of 10 times the plasma IC50. The use of these data for establishing patient-focused candidate selection criteria is exemplified with the characterization of compound 8, which is projected to sustain the desired level of target engagement at a dose of 45 mg qd. PMID- 27194202 TI - Gymnopeptides A and B, Cyclic Octadecapeptides from the Mushroom Gymnopus fusipes. AB - Mycochemical study of the mushroom Gymnopus fusipes led to the discovery of two new cyclopeptides. The two compounds, named as gymnopeptides A and B, are unprecedented highly N-methylated cyclic octadecapeptides. Detailed spectroscopic studies, Marfey's analysis, and a preliminary molecular modeling study suggested that both are natural cyclic beta hairpins. The isolated compounds exhibited striking antiproliferative activity on several human cancer cell lines, with nanomolar IC50 values. PMID- 27194203 TI - High-Q side-coupled semi-2D-photonic crystal cavity. AB - High-Q semi-2D-photonic crystal cavities with a tapered edge and side-coupled bus waveguide are demonstrated. With a quadratic design, the unloaded cavity presents a theoretical ultrahigh quality factor up to 6.7 * 10(7) for the condition that there are mere 34 holes in the propagated direction, which is pretty close to the 2D and 1D counterpart. Combined with a side-coupled bus waveguide, an all-pass type cavity with a loaded quality factor (Q) of over 2.4 * 10(4) and an extinction ratio over 10 dB are experimentally demonstrated. An experimental loaded Q up to 1.1 * 10(5) are also achieved by tuning the coupling between the cavity and the bus waveguide, which is much larger than any reported surface-mode cavity. This cavity is quite suitable for sensors, filters and especially optomechanical devices thanks to the mechanical stability of the cavity and flexibility of the bus waveguide. PMID- 27194204 TI - Super-resolution microscopy reveals structural diversity in molecular exchange among peptide amphiphile nanofibres. AB - The dynamic behaviour of supramolecular systems is an important dimension of their potential functions. Here, we report on the use of stochastic optical reconstruction microscopy to study the molecular exchange of peptide amphiphile nanofibres, supramolecular systems known to have important biomedical functions. Solutions of nanofibres labelled with different dyes (Cy3 and Cy5) were mixed, and the distribution of dyes inserting into initially single-colour nanofibres was quantified using correlative image analysis. Our observations are consistent with an exchange mechanism involving monomers or small clusters of molecules inserting randomly into a fibre. Different exchange rates are observed within the same fibre, suggesting that local cohesive structures exist on the basis of beta sheet discontinuous domains. The results reported here show that peptide amphiphile supramolecular systems can be dynamic and that their intermolecular interactions affect exchange patterns. This information can be used to generate useful aggregate morphologies for improved biomedical function. PMID- 27194205 TI - Mini-pillar array for hydrogel-supported 3D culture and high-content histologic analysis of human tumor spheroids. AB - Three-dimensional (3D) cancer cell culture models mimic the complex 3D organization and microenvironment of human solid tumor tissue and are thus considered as highly predictive models representing avascular tumor regions. Confocal laser scanning microscopy is useful for monitoring drug penetration and therapeutic responses in 3D tumor models; however, photonic attenuation at increasing imaging depths and limited penetration of common fluorescence tracers are significant technical challenges to imaging. Immunohistological staining would be a good alternative, but the preparation of tissue sections from rather fragile spheroids through fixing and embedding procedures is challenging. Here we introduce a novel 3 * 3 mini-pillar array chip that can be utilized for 3D cell culturing and sectioning for high-content histologic analysis. The mini-pillar array chip facilitated the generation of 3D spheroids of human cancer cells within hydrogels such as alginate, collagen, and Matrigel. As expected, visualization of the 3D distribution of calcein AM and doxorubicin by optical sectioning was limited by photonic attenuation and dye penetration. The integrity of the 3D microtissue section was confirmed by immunostaining on paraffin sections and cryo-sections. The applicability of the mini-pillar array for drug activity evaluation was tested by measuring viability changes in spheroids exposed to anti-cancer agents, 5-fluorouracil and tirapazamine. Thus, our novel mini-pillar array platform can potentially promote high-content histologic analysis of 3D cultures and can be further optimized for field-specific needs. PMID- 27194207 TI - Graphene oxide-peptide nanoassembly as a general approach for monitoring the activity of histone deacetylases. AB - A novel fluorescent sensor using graphene oxide (GO)-peptide nanoassembly is developed for histone deacetylases (HDACs) based on deacetylation mediated cleavage of substrate peptides, which provides a simple, cost-effective platform for monitoring the activity of HDACs. PMID- 27194206 TI - A Modified Thyroid Imaging Reporting and Data System (mTI-RADS) For Thyroid Nodules in Coexisting Hashimoto's Thyroiditis. AB - To develop a conventional ultrasound (US) modified Thyroid Imaging Reporting and Data System (mTI-RADS) to stratify the malignancy risk of thyroid nodule in coexisting Hashimoto's thyroiditis (HT). The study included 138 malignant and 292 benign thyroid nodules confirmed by cytological or histopathological results. The risk score (RS) for each significant US feature was estimated by multiplying corresponding regression coefficient and the total score for each nodule was defined as the sum of these individual scores. The mTI-RADS was established according to the total RS and divided into category 3, 4a, 4b, 4c and 5. Marked hypoechogenicity, taller-than-wide shape, poorly-defined margin, microcalcification or macrocalcification and halo sign absence were statistically significant US features in prediction of thyroid malignancy (all p < 0.05). The total RS for each nodule was defined as following: RS = 2.1* (if marked hypoechogenicity) + 1.2* (if taller-than-wide shape) + 1.7* (if no halo sign) + 0.6* (if poorly-defined margin) + 1.2* (if microcalcification or macrocalcification). The malignancy rates in mTI-RADS category 3, 4a, 4b, 4c and 5 nodules were 3.7%, 19.3%, 38.1%, 62.7% and 94.1%, respectively, with significant differences among different categories (P < 0.001). The mTI-RADS category may facilitate subsequent treatment management in HT patients. PMID- 27194208 TI - Protozoan indicators and extracellular polymeric substances alterations in an intermittently aerated membrane bioreactor treating mature landfill leachate. AB - A membrane bioreactor was operated under intermittent aeration and various organic loading rates (OLR: 0.070, 0.159 and 0.291 g COD L-1 d-1) to remove carbon and nitrogen from mature landfill leachate, where external carbon source (glycerol) addition resulted in effective nitrate removal. A relative increase in soluble microbial product (SMP) over extracellular polymeric substances (EPS) was observed at the highest OLR and glycerol addition, whereas no membrane biofouling occurred. SMP (proteins and carbohydrates) and carbohydrate EPS correlated positively and negatively, respectively, with suspended solids and transmembrane pressure (TMP). Moreover, proteinous SMP significantly correlated with carbon and nitrogen load. Principal component analysis also revealed the influence of leachate organic and nitrogen content on biomass production, TMP and sessile ciliate densities. Although filamentous index (FI) was sustained at high levels (3-4), with Haliscomenobacter hydrossis being the main filamentous bacterium identified, no bulking phenomena occurred. High glycerol addition resulted in a rapid increase in sessile ciliate population. Increased Epistylis and Vorticella microstoma population was detected by microscopic examination during high glycerol addition, while a remarkable Rhogostoma population (supergroup Rhizaria) was identified by molecular techniques. The contribution of Rhizaria in nitrogen processes may lead to the dominance of Rhogostoma during landfill leachate treatment. PMID- 27194209 TI - Clinicopathogenomic analysis of mismatch repair proficient colorectal adenocarcinoma uncovers novel prognostic subgroups with differing patterns of genetic evolution. AB - Cancer somatic genetic evolution is a direct contributor to heterogeneity at the clonal and molecular level in colorectal adenocarcinoma (COAD). We sought to determine the extent to which genetic evolution may be detected in COAD in routinely obtained single clinical specimens and establish clinical significance with regard to clinicopathologic and outcome data. One hundred and twenty three cases of routinely collected mismatch repair proficient COAD were sequenced on the Illumina Truseq Amplicon assay. Measures of intratumoral heterogeneity and the preferential timing of mutational events were assessed and compared to clinicopathologic data. Survival subanalysis was performed on 55 patients. Patient age (p = 0.013) and specimen percent tumor (p = 0.033) was associated with clonal diversity, and biopsy (p = 0.044) and metastasis (p = 0.044) returned fewer mutations per case. APC and TP53 mutations preferentially occurred early while alterations in FBXW7, FLT3, SMAD4, GNAS and PTEN preferentially occurred as late events. Temporal heterogeneity was evident in KRAS and PIK3CA mutations. Hierarchical clustering revealed a TP53 mutant subtype and a MAPK-PIK3CA subtype with differing patterns of late mutational events. Survival subanalysis showed a decreased median progression free survival for the MAPK-PIK3CA subtype (8 months vs. 13 months; univariate logrank p = 0.0380, cox model p= 0.018). Neoadjuvant therapy associated mutations were found for ERBB2 (p = 0.0481) and FBXW7 (p = 0.015). Our data indicate novel molecular subtypes of mismatch repair proficient COAD display differing patterns of genetic evolution which correlate with clinical outcomes. Furthermore, we report treatment acquired and/or selected mutations in ERBB2 and FBXW7. PMID- 27194210 TI - Comparative B-mode and Doppler renal ultrasonography with histopathological findings in dogs positive for canine visceral leishmaniasis. AB - Morphological parameters and renal flow were assessed and measured in six clinically healthy dogs with negative serological and parasitological examinations for canine visceral leishmaniasis (CVL) and six dogs with CVL positive serological and parasitological tests and asymptomatic condition of the disease. Kidney length and diameter were measured and compared with the aorta/kidney ratio. Alterations in flow were measured using the flow velocity (cm/s) and resistance index (RI). Renal function was assessed by serum biochemical examination (urea, creatine, total proteins, albumin, and globulin) and urinalysis. CVL-positive animals presented heterogeneous kidney echotexture, reduced vascular flow, hypoperfusion, lesser visualization of the arcuate arteries, high RI values (1.06 +/- 0.28 for the right kidney and 1.10 +/- 0.30 for the left kidney), reduced diastolic flow, and high systolic peak. They also presented positive creatine/RI correlation and between the renal artery vascular flow and kidney diameter. Histopathological analysis of CVL-positive animals was compatible and confirmed hemodynamic changes observed by Doppler ultrasound. The findings in the present study showed that Doppler ultrasonography is a valid method to assess and detect alterations in flow in renal pathological processes with kidney vascular damage, as in the case of leishmaniasis, and can help in the diagnosis of animals with this infection. Microsc. Res. Tech. 79:637-645, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27194213 TI - A cortically-inspired model for inverse kinematics computation of a humanoid finger with mechanically coupled joints. AB - The human hand's versatility allows for robust and flexible grasping. To obtain such efficiency, many robotic hands include human biomechanical features such as fingers having their two last joints mechanically coupled. Although such coupling enables human-like grasping, controlling the inverse kinematics of such mechanical systems is challenging. Here we propose a cortical model for fine motor control of a humanoid finger, having its two last joints coupled, that learns the inverse kinematics of the effector. This neural model functionally mimics the population vector coding as well as sensorimotor prediction processes of the brain's motor/premotor and parietal regions, respectively. After learning, this neural architecture could both overtly (actual execution) and covertly (mental execution or motor imagery) perform accurate, robust and flexible finger movements while reproducing the main human finger kinematic states. This work contributes to developing neuro-mimetic controllers for dexterous humanoid robotic/prosthetic upper-extremities, and has the potential to promote human robot interactions. PMID- 27194214 TI - The role of the equilibrative nucleoside transporter 1 on tissue and fetal distribution of ribavirin in the mouse. AB - Ribavirin is used for the treatment of hepatitis C virus (HCV) infection. The equilibrative nucleoside transporter 1 (ENT1) expressed in hepatocytes transports ribavirin into the liver, the site of efficacy of the drug. However, it is still unclear whether ENT1 plays a dominant role in the hepatic distribution of the drug in vivo. In addition, due to fetal toxicity, administration of ribavirin to pregnant women with HCV infection is contraindicated. ENT1 might play a role in the fetal distribution and therefore the fetal toxicity of ribavirin. The aim of the present study was to investigate the in vivo contribution of ENT1 to the tissue distribution of ribavirin. When compared with that in Ent1(+/+) mice, the ribavirin tissue to plasma concentration ratio (including phosphorylated metabolites) in Ent1(-/-) mice at 15 min and 6 h after intravenous [(3) H] ribavirin (3 mg/kg) administration was consistently and significantly decreased in the liver and the pancreas. Likewise, when compared with the Ent1(+/+) mice, the fetal distribution of ribavirin at 15 min after administration was significantly reduced in Ent1(-/-) fetuses and placenta. In contrast, there was no significant difference between Ent1(+/+), Ent1(+/-) and Ent1(-/-) mice in the fetal or placental to maternal plasma ribavirin concentration ratio at 2 h after ribavirin administration. The findings in the present study suggest that ENT1 plays a pivotal role in the distribution of ribavirin into tissues including the liver and pancreas, but affects only the rate, but not the extent, of ribavirin distribution into the fetus. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27194212 TI - Primary hyperparathyroidism. AB - Primary hyperparathyroidism (PHPT) is a common disorder in which parathyroid hormone (PTH) is excessively secreted from one or more of the four parathyroid glands. A single benign parathyroid adenoma is the cause in most people. However, multiglandular disease is not rare and is typically seen in familial PHPT syndromes. The genetics of PHPT is usually monoclonal when a single gland is involved and polyclonal when multiglandular disease is present. The genes that have been implicated in PHPT include proto-oncogenes and tumour-suppressor genes. Hypercalcaemia is the biochemical hallmark of PHPT. Usually, the concentration of PTH is frankly increased but can remain within the normal range, which is abnormal in the setting of hypercalcaemia. Normocalcaemic PHPT, a variant in which the serum calcium level is persistently normal but PTH levels are increased in the absence of an obvious inciting stimulus, is now recognized. The clinical presentation of PHPT varies from asymptomatic disease (seen in countries where biochemical screening is routine) to classic symptomatic disease in which renal and/or skeletal complications are observed. Management guidelines have recently been revised to help the clinician to decide on the merits of a parathyroidectomy or a non-surgical course. This Primer covers these areas with particular attention to the epidemiology, clinical presentations, genetics, evaluation and guidelines for the management of PHPT. PMID- 27194216 TI - Esophageal acid sensitivity and mucosal integrity in patients with functional heartburn. AB - BACKGROUND: Patients with functional heartburn (FH) experience troublesome heartburn that is not related to gastroesophageal reflux. The etiology of the heartburn sensation in FH patients is unknown. In patients with reflux disease, esophageal hypersensitivity seems associated with impaired mucosal integrity. We aimed to determine esophageal sensitivity and mucosal integrity in FH and non erosive reflux disease (NERD) patients. METHODS: In this prospective experimental study, we performed an acid perfusion test and upper endoscopy with biopsies in 12 patients with NERD and nine patients with FH. Mucosal integrity was measured during endoscopy using electrical tissue impedance spectroscopy and biopsy specimens were analyzed in Ussing chambers for transepithelial electrical resistance and transepithelial permeability. KEY RESULTS: Lag time to heartburn perception was significantly longer in FH patients (median 12 min) than in NERD patients (median 3 min). Once perceived, intensity of heartburn was scored equal with median visual analog scale 6.5 and 7.1 respectively. Esophageal mucosal integrity was also comparable between FH and NERD patients, both in vivo extracellular impedance and ex vivo transepithelial resistance and permeability were similar. CONCLUSIONS & INFERENCES: Patients with FH did not show acid hypersensitivity as seen in patients with NERD. However, once perceived, intensity of heartburn is similar. Esophageal mucosal integrity is similar between NERD and FH patients, and is therefore unlikely to be the underlying cause of the observed difference in esophageal acid perception. PMID- 27194215 TI - Bioactivity of 2'-deoxyinosine-incorporated aptamer AS1411. AB - Aptamers can be chemically modified to enhance nuclease resistance and increase target affinity. In this study, we performed chemical modification of 2' deoxyinosine in AS1411, an anti-proliferative G-rich oligodeoxynucleotide aptamer, which binds selectively to the nucleolin protein. Its function was augmented when 2'-deoxyinosine was incorporated at positions 12, 13, 15, and 24 of AS1411, respectively. In addition, double incorporation of 2'-deoxyinosine at positions 12 and 24 (FAN-1224dI), 13 and 24 (FAN-1324dI), and 15 and 24 (FAN 1524dI) promoted G-quartet formation, as well as inhibition of DNA replication and tumor cell growth, and induced S-phase cell cycle arrest. In further animal experiments, FAN-1224dI, FAN-1324dI and FAN-1524dI resulted in enhanced treatment effects than AS1411 alone. These results suggested that the position and number of modification substituents in AS1411 are critical parameters to improve the diagnostic and therapeutic function of the aptamer. Structural investigations of the FAN-1524dI/nucleolin complex structure, using molecular dynamics simulation, revealed the critical interactions involving nucleolin and 2'-dI incorporated AS1411 compared with AS1411 alone. These findings augment understanding of the role of 2'-deoxyinosine moieties in interactive binding processes. PMID- 27194217 TI - Low-Chlorinated Non-Dioxin-like Polychlorinated Biphenyls Present in Blood and Breast Milk Induce Higher Levels of Reactive Oxygen Species in Neutrophil Granulocytes than High-Chlorinated Congeners. AB - Despite their ban several decades ago, polychlorinated biphenyls (PCBs) still pose a health threat to human beings due to their persistent and accumulative nature and continued presence in the environment. Non-dioxin-like (NDL)-PCBs have earlier been found to have effects on the immune system, including human neutrophil granulocytes. The aim of this study was to investigate the differences between ortho-chlorinated NDL-PCBs with a low or high degree of chlorination in their capability to induce the production of reactive oxygen species (ROS) in human neutrophil granulocytes in vitro. We used some of the congeners occurring at the highest levels in blood, breast milk and food: PCB 52 representing the low chlorinated congeners and PCB 180 the high-chlorinated congeners. In addition, the extensively studied PCB 153 was included as a reference compound. ROS production was assessed with the luminol-amplified chemiluminescence and DCF fluorescence assays. The involvement of intracellular signalling mechanisms was investigated using different pharmacological substances. At high concentrations (10-20 MUM), PCB 52 induced more ROS than PCB 153 and PCB 180. The role of extracellular signal-regulated kinase (ERK) 1/2 and/or ERK 5 signalling in PCB induced ROS production was implicated through the reduction in ROS in the presence of the specific inhibitor U0126, whereas reduced ROS production after the use of SB203580 and SP600125 indicated the involvement of the p38 mitogen activated protein kinase (MAPK) and c-Jun amino-terminal kinase (JNK) pathways, respectively. In addition, the calcineurin inhibitor FK-506, the intracellular calcium chelator BAPTA-AM and the antioxidant vitamin E reduced the levels of ROS. The intracellular signalling mechanisms involved in ROS production in human neutrophil granulocytes appeared to be similar for PCB 52, PCB 153 and PCB 180. Based on the results from the present and previous studies, we conclude that for abundant ortho-chlorinated PCBs found in the blood, low-chlorinated congeners induce higher production of ROS in neutrophil granulocytes than high-chlorinated congeners. This could be relevant during acute exposure scenarios when high concentrations of PCBs are present. PMID- 27194218 TI - Nutritional properties of the largest bamboo fruit Melocanna baccifera and its ecological significance. AB - Melocanna baccifera is a unique bamboo which produces the largest fruits in the grass family. Its gregarious flowering once in 45-50 years in north east India and adjacent regions is a botanical enigma, resulting in a glut of fruits. Proper utilization of M. baccifera fruits is not extant, and huge quantities of fruits are left underexploited due to lack of scientific information on their chemical composition and nutritional potential. Here we report the nutritional properties of M. baccifera fruits, and the ecological significance of its fruiting. This pear-shaped, fleshy bamboo fruit is rich in amino acids (lysine, glutamic acid), sugars (sucrose, glucose, fructose) and phenolics (ferulic acid). Protein content (free, bound) in M. baccifera fruits is very low. Fruits are rich in saturated fatty acids (palmitic acid), minerals (potassium), and only B series vitamins (B3) are detected in them. Rat feeding experiments showed that M. baccifera fruit alone is not a complete food, but with other protein supplements, it is a valuable food additive. This study could lead to better utilization of M. baccifera fruits during future flowering/fruiting events. These results could also help in the successful management of rodent outbreaks and other ecological problems associated with M. baccifera fruiting. PMID- 27194221 TI - Eliminate slogans and remove barriers to pride in work. PMID- 27194220 TI - Serum interleukin-6 levels in response to biologic treatment in patients with psoriasis. AB - OBJECTIVES: Psoriasis is a chronic autoimmune disease involving a complex network of cytokines such as interleukin (IL)-6. We tested the hypothesis that serum IL-6 level is a useful indicator of disease activity and predicts the treatment response to biologics in patients with psoriasis. METHODS: We analyzed 113 psoriasis patients treated with biologics (73 with infliximab [IFX], 24 with adalimumab [ADA], and 16 with ustekinumab [UST]) in our hospital. Disease severity was assessed using the Psoriasis Area and Severity Index (PASI) score, and Disease Activity Score 28 based on C-reactive protein (DAS28-CRP). RESULTS: Before treatment, serum IL-6 levels significantly correlated with PASI scores in patients with psoriasis vulgaris (r = 0.432, p = 0.001) and with DAS28-CRP in patients with psoriatic arthritis (r = 0.469, p = 0.010). Serum IL-6 levels were significantly decreased by IFX (from 4.8 to 1.5) and ADA (from 2.5 to 1.4) therapy. In psoriatic arthritis, serum IL-6 levels at the endpoint tended to be lower in patients who achieved DAS28-CRP <2.3 (European League Against Rheumatism remission criteria) than in patients who did not. CONCLUSION: Serum IL-6 level may be a useful biomarker for assessing disease activity in patients with psoriasis and for predicting responsiveness of joint symptoms to biologic treatment. PMID- 27194222 TI - CLIP-COSY: A Clean In-Phase Experiment for the Rapid Acquisition of COSY-type Correlations. AB - The COSY experiment is an essential homonuclear 2D NMR experiment for the assignment of resonances. Its multiplet line shape, however, is often overly complicated, potentially leads to signal intensity losses, and is responsible for long minimum overall acquisition times. Herein, we present CLIP-COSY, a COSY-type experiment yielding clean in-phase peaks. It can be recorded within a few minutes and benefits from enhanced signal intensities for most cross-peaks. In combination with non-uniform sampling, the experiment times can be further reduced, and the in-phase multiplets enable the application of modern homonuclear decoupling techniques in both dimensions. As antiphase cancelations are avoided, CLIP-COSY can also be applied to macromolecules and other samples with broadened lines. PMID- 27194219 TI - The Oxygen Dilemma: A Severe Challenge for the Application of Monooxygenases? AB - Monooxygenases are promising catalysts because they in principle enable the organic chemist to perform highly selective oxyfunctionalisation reactions that are otherwise difficult to achieve. For this, monooxygenases require reducing equivalents, to allow reductive activation of molecular oxygen at the enzymes' active sites. However, these reducing equivalents are often delivered to O2 either directly or via a reduced intermediate (uncoupling), yielding hazardous reactive oxygen species and wasting valuable reducing equivalents. The oxygen dilemma arises from monooxygenases' dependency on O2 and the undesired uncoupling reaction. With this contribution we hope to generate a general awareness of the oxygen dilemma and to discuss its nature and some promising solutions. PMID- 27194223 TI - Generation of a mouse model for a conditional inactivation of Gtf2i allele. AB - The multifunctional transcription factor TFII-I encoded by the Gtf2i gene is expressed at the two-cell stage, inner cell mass, trophectoderm, and early gastrula stages of the mouse embryo. In embryonic stem cells, TFII-I colocalizes with bivalent domains and depletion of Gtf2i causes embryonic lethality, neural tube closure, and craniofacial defects. To gain insight into the function of TFII I during late embryonic and postnatal stages, we have generated a conditional Gtf2i null allele by flanking exon 3 with loxP sites. Crossing the floxed line with the Hprt-Cre transgenic mice resulted in inactivation of Gtf2i in one-cell embryo. The Cre-mediated deletion of exon 3 recapitulates a genetic null phenotype, indicating that the conditional Gtf2i line is a valuable tool for studying TFII-I function during embryonic development. genesis 54:407-412, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27194225 TI - Comment on "Is the regulation of the electronic properties of organic molecules by polynuclear superhalogens more effective than that by mononuclear superhalogens? A high-level ab initio case study" by M.-M. Li, J.-F. Li, H.-C. Bai, Y.-Y. Sun, J.-L. Li and B. Yin, Phys. Chem. Chem. Phys., 2015, 17, 20338. AB - The Outer Valence Green Function (OVGF) and coupled-cluster singles and doubles plus approximate triples, or CCSD(T), methods yield similar results for the vertical detachment energies of superhalides studied recently by Li et al. The success of the OVGF method contradicts claims by Li et al. in their recent article. PMID- 27194224 TI - Influence of cuff material on blood flow restriction stimulus in the upper body. AB - The purpose of this study was to examine the acute skeletal muscle and perceptual responses to blood flow restriction (BFR) exercise to failure between narrow nylon and elastic inflatable cuffs at rest and during exercise. Torque and muscle thickness was measured pre, post, and 5, 20, 40, and 60 min post-exercise with muscle activation being measured throughout exercise. Resting arterial occlusion pressure was different between the nylon [139 (14) mmHg] and elastic [246 (71) mmHg, p < 0.001] cuffs. However, when exercising at 40 % of each cuff's respective arterial occlusion pressure [nylon: 57 (7) vs. elastic: 106 (38) mmHg, p < 0.001], there were no differences in repetitions to failure, torque, muscle thickness, or muscle activation between the cuffs. Exercising with cuffs of different material but similar width resulted in the same acute muscular response when the cuffs were inflated to a pressure relative to each individual cuff. PMID- 27194226 TI - Aneuploidy screening by non-invasive prenatal testing in twin pregnancy. AB - OBJECTIVES: To describe our experience with non-invasive prenatal testing (NIPT) in twin pregnancy. METHODS: Two sets of maternal blood samples from twin pregnancies were analyzed at our laboratory using NIPT: 115 stored samples from pregnancies with known outcome (Clinical Study A) and 487 prospectively collected samples for which outcomes were requested from providers (Clinical Study B). NIPT was used to screen for the presence of fetal aneuploidy on chromosomes 13, 18, 21, X and Y in all cases, and results were compared with outcomes when known. RESULTS: In Clinical Study A, all 115 samples were classified correctly by NIPT: three cases of trisomy 21 (one fetus affected), one of monochorionic trisomy 18 (both fetuses affected) and 111 euploid. In Clinical Study B, a NIPT result was reported for 479 (98.4%) of the 487 samples. Aneuploidy was detected or suspected in nine (1.9%) cases: seven cases of trisomy 21 detected, one case of trisomy 21 suspected and one case with trisomy 21 detected and trisomy 18 suspected. Information on aneuploidy outcome was available for 171 (35.7%) cases in Clinical Study B. Of the nine cases with aneuploidy detected or suspected, six were confirmed to be a true positive in at least one twin based on karyotype or birth outcome and two were suspected to be concordant based on ultrasound findings; the one known discordant result was for the aneuploidy suspected case. No false negatives were reported. CONCLUSION: NIPT performed well in the detection of trisomy 21 in twin pregnancy, with a combined false-positive frequency for trisomies 13, 18 and 21 of 0% for Clinical Study A and 0.2% for Clinical Study B. (c) 2016 Illumina. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. PMID- 27194228 TI - Experimental new automatic tools for robotic stereotactic neurosurgery: towards "no hands" procedure of leads implantation into a brain target. AB - The use of robotics in neurosurgery and, particularly, in stereotactic neurosurgery, is becoming more and more adopted because of the great advantages that it offers. Robotic manipulators easily allow to achieve great precision, reliability, and rapidity in the positioning of surgical instruments or devices in the brain. The aim of this work was to experimentally verify a fully automatic "no hands" surgical procedure. The integration of neuroimaging to data for planning the surgery, followed by application of new specific surgical tools, permitted the realization of a fully automated robotic implantation of leads in brain targets. An anthropomorphic commercial manipulator was utilized. In a preliminary phase, a software to plan surgery was developed, and the surgical tools were tested first during a simulation and then on a skull mock-up. In such a way, several tools were developed and tested, and the basis for an innovative surgical procedure arose. The final experimentation was carried out on anesthetized "large white" pigs. The determination of stereotactic parameters for the correct planning to reach the intended target was performed with the same technique currently employed in human stereotactic neurosurgery, and the robotic system revealed to be reliable and precise in reaching the target. The results of this work strengthen the possibility that a neurosurgeon may be substituted by a machine, and may represent the beginning of a new approach in the current clinical practice. Moreover, this possibility may have a great impact not only on stereotactic functional procedures but also on the entire domain of neurosurgery. PMID- 27194227 TI - Alteration of functional connectivity in autism spectrum disorder: effect of age and anatomical distance. AB - Autism spectrum disorder (ASD) is associated with disruption of local- and long range functional connectivity (FC). The direction of those changes in FC (increase or decrease), however, is inconsistent across studies. Further, age dependent changes of distance-specific FC in ASD remain unclear. In this study, we used resting-state functional magnetic resonance imaging data from sixty-four typical controls (TC) and sixty-four patients with ASD, whom we further classified into child (<11 years), adolescent (11-18 years) and adult cohorts (>18 years). Functional connectivity (FC) analysis was conducted at voxel level. We employed a three-way analysis of covariance on FC to conduct statistical analyses. Results revealed that patients with ASD had lower FC than TC in cerebellum, fusiform gyrus, inferior occipital gyrus and posterior inferior temporal gyrus. Significant diagnosis-by-distance interaction was observed in ASD patients with reduced short-range and long-range FC in posterior cingulate cortex and medial prefrontal cortex. Importantly, we found significant diagnosis-by-age by-distance interaction in orbitofrontal cortex with short-range FC being lower in autistic children, but -to a less extent- higher in autistic adults. Our findings suggest a major role of connection length in development changes of FC in ASD. We hope our study will facilitate deeper understanding of the neural mechanisms underlying ASD. PMID- 27194229 TI - Effects of theta-rhythm transcranial alternating current stimulation (4.5 Hz tACS) in patients with clozapine-resistant negative symptoms of schizophrenia: a case series. AB - Our aim was to assess the efficacy and safety of theta-rhythm transcranial Alternating Current Stimulation (4.5 Hz-tACS) in patients with clozapine resistant symptoms of schizophrenia. In an open case series, 3 patients received 20 sessions of 4.5 Hz-tACS (20 min, 2 mA) applied over the dorsolateral prefrontal cortex. The patients exhibited a decrease of negative symptoms (-10 %), general symptoms (-18 %) and an improvement of insight into the illness (-25 %). 4.5 Hz-tACS might be a suitable alternative treatment for clozapine-resistant symptoms of schizophrenia. PMID- 27194230 TI - Seasonal variation and enrichment of metals in sediments of Rosetta branch, Nile River, Egypt. AB - This study investigated heavy metal pollution in sediments of the Rosetta branch of the River Nile of Egypt to quantify the toxic distribution potential of metals into the surrounding environment. Sediment samples were collected at 9 sites during in four seasons. Organic matter and total metal concentrations were determined using loss on ignition and inductively coupled plasma spectrometry, respectively. Principal component analysis has been applied to evaluate the metal sources and the relationships between metals in sediments. Metal concentrations showed the following order: winter > autumn > spring > summer. Mean concentrations of Cu, Zn, Cd, and Pb in sediments were above the average background value of metals in shale. Pb and Cd showed higher enrichment during all seasons at stations N3/N4, Zn at stations N1 to N4, and Cu at stations N6/N8. The variations in heavy metal total concentration and organic matter are due to different input sources, physico-chemical conditions, and adsorption/precipitation/redox conditions in sediments. Mean values of Geo accumulation index (Igeo) for Fe, Mn, and Cu were below 0 which were classified as unpolluted during spring, summer, and autumn, except Cu increased from unpolluted to moderately polluted during winter. Igeo values for Cd, Pb, and Zn increased from unpolluted-moderately polluted to highly-very highly polluted during autumn and winter. Pollution Load Index was recorded in highest values during winter, especially at Fuwwah/Basioun and in lowest values during summer at after the Edfina Barrage/before Kafer El-Zayat due to industrial/human activities. Both natural and anthropogenic sources contributed to the metal accumulations in sediments, and industrial, agricultural, and municipal sewage effluents discharged from non-point sources may be the main anthropogenic sources for metals in the Rosetta branch. PMID- 27194231 TI - Memory loss risk assessment for the students nearby high-voltage power lines-a case study. AB - With increasing sources of alternating current electromagnetic fields (EMFs) in everyday life, their possible harmful effects on human health are a main area of concern in many countries. Given that children are the most valuable assets of each country, it is of utmost importance to study the effect(s) of EMF exposure on various health aspects of members within this age group. The present research is the first systematic study of the effects of exposure to electric substations on the memory status of male students in the age group of 10 to 12 years. The flux density values of extremely low frequency magnetic field were measured at four elementary schools in Tehran in accordance with IEEE std 644-1994. The device was 3-axis (X, Y, and Z) Gauss Meter, model: TES-1394. The students from two schools nearby a high voltage electricity substation (at distances of 30 and 50 m) were selected as the exposed group, and the students of two other schools at further distances of 1390 and 610 m were considered as the control group. To determine the status of working memory in the students, the questionnaire was adapted from Wechsler Intelligence Scale for Children (WISC-IV). The completed questionnaires were analyzed by t test and chi-square using SPSS 20. The average magnetic flux density was 0.245 MUT at case schools and 0.164 MUT at control schools, P < 0.01. The demographic characteristics of the students in the two groups were not statistically different. However, the difference in working memory was significant at the level of 5 %. The results of the questionnaire data showed that students in the control group had better working memory compared to students in case group. The findings revealed a reverse correlation between magnetic flux density and working memory of students (R = -0.255). It is concluded that extremely low frequency magnetic field exposure may have a negative impact on the working memory of children, but further studies are necessary to reach a definitive conclusion. PMID- 27194232 TI - How does the selection of landscape classification schemes affect the spatial pattern of natural landscapes? An assessment on a coastal wetland site in southern Italy. AB - It is widely known that thematic resolution affects spatial pattern and landscape metrics performances. In literature, data dealing with this issue usually refer to a specific class scheme with its thematic levels. In this paper, the effects of different land cover (LC) and habitat classification schemes on the spatial pattern of a coastal landscape were compared. One of the largest components of the Mediterranean wetland system was considered as the study site, and different schemes widely used in the EU were selected and harmonized with a common thematic resolution, suitable for habitat discrimination and monitoring. For each scheme, a thematic map was produced and, for each map, 28 landscape metrics were calculated. The landscape composition, already in terms of number of classes, class area, and number of patches, changes significantly among different classification schemes. Landscape complexity varies according to the class scheme considered and its underlying semantics, depending on how the different types aggregate or split when changing class scheme. Results confirm that the selection of a specific class scheme affects the spatial pattern of the derived landscapes and consequently the landscape metrics, especially at class level. Moreover, among the classification schemes considered, EUNIS seems to be the best choice for a comprehensive representation of both natural and anthropogenic classes. PMID- 27194233 TI - A framework for assessment and characterisation of municipal solid waste landfill leachate: an application to the Turbhe landfill, Navi Mumbai, India. AB - Rapid industrialisation, growing population and changing lifestyles are the root causes for the generation of huge amounts of solid waste in developing countries. In India, disposal of municipal solid waste (MSW) through open dumping is the most common waste disposal method. Unfortunately, leachate generation from landfill is high due to the prolonged and prominent monsoon season in India. As leachate generation rate is high in most of the tropical countries, long-term and extensive monitoring efforts are expected to evaluate actual environmental pollution potential due to leachate contamination. However, the leachate characterisation involves a comprehensive process, which has numerous shortcomings and uncertainties possibly due to the complex nature of landfilling process, heterogeneous waste characteristics, widely varying hydrologic conditions and selection of analytes. In order to develop a sustainable MSW management strategy for protecting the surface and ground water resources, particularly from MSW landfill leachate contamination, assessment and characterisation of leachate are necessary. Numerous studies have been conducted in the past to characterise leachate quality from various municipal landfills; unfortunately, none of these propose a framework or protocol. The present study proposes a generic framework for municipal landfill leachate assessment and characterisation. The proposed framework can be applied to design any type of landfill leachate quality monitoring programme and also to facilitate improved leachate treatment activities. A landfill site located at Turbhe, Navi Mumbai, India, which had not been investigated earlier, has been selected as a case study. The proposed framework has been demonstrated on the Turbhe landfill site which is a comparatively new and the only sanitary landfill in Navi Mumbai. PMID- 27194236 TI - Rescue Medicine for Epilepsy: New Options for Education Settings. AB - The American Academy of Pediatrics (AAP) recently published a clinical report recommending expanded options for seizure rescue medications in the school setting. School nurses rely on prescribing professionals for medical orders to manage children with epilepsy in the school setting. The report suggests additional medications beyond rectal diazepam gel along with discussing the purpose of the medications, the variations in prescribing practices for seizure rescue medications, inconsistencies in legislation based on jurisdictions, and the need for school medical orders for students with epilepsy. There are many issues faced by school personnel when caring for students with a diagnosis of epilepsy, chief among them the presence of licensed health professions for the school to be able to respond quickly and appropriately in the event of a seizure. School nurses can assist health care providers in determining the rescue medication most easily delivered and monitored in the variety of activities that are part of the school experience, including transportation to and from school, field trips, and before- and after-school activities, all beyond the regular classroom setting. PMID- 27194235 TI - Treatment of irritable bowel syndrome with a novel colonic irrigation system: a pilot study. AB - BACKGROUND: Medical treatments for irritable bowel syndrome (IBS) are often disappointing. A colonic irrigation system, the Ashong colonic irrigation apparatus (ACIA), was designed as a patient-administered device for defecation disorders. This pilot study evaluated the efficacy and safety of ACIA for IBS. METHODS: Eighteen patients, 12 with constipation-dominant IBS (IBS-C) and 6 with diarrhea-dominant IBS (IBS-D) group, were studied. Patients were randomized into treatments of 1-4 weeks. Colonic irrigation was performed twice daily for 6 consecutive days per week. To determine the response to treatment, bowel movement frequency, stool consistency, abdominal pain, patient satisfaction with bowel movements, and distress/discomfort due to symptoms were assessed. RESULTS: The scores of abdominal pain (p < 0.001), satisfaction (p < 0.001), and distress/discomfort (p < 0.001) improved significantly. The frequency of bowel movements in the IBS-C group increased from 1.68 to 3.78 times per week (p < 0.001). The occurrence of Bristol Stool Scale type 1 and 2 stool passage decreased from 45 to 13 % (p = 0.009) in the IBS-C group and type 6 and 7 stools decreased from 62 to 28 % (p = 0.005) in the IBS-D group. Only mild adverse events occurred, and all patients completed treatment. CONCLUSIONS: Colonic irrigation with ACIA is safe and can improve abdominal pain, constipation, and diarrhea associated with IBS. Patients were more satisfied with their bowel movements and found their symptoms were less disturbing. Larger studies on long term efficacy and quality of life and on placebo effects are needed. PMID- 27194234 TI - Distribution and risk assessment of selected organochlorine pesticides in Kyzyl Kairat village from Kazakhstan. AB - Concentrations of selected organochlorine pesticides (OCPs), i.e., 4,4' dichlorodiphenyltrichloroethane (p,p'-DDT), its metabolites (p,p'-DDE, p,p'-DDD), and hexachlorocyclohexanes (HCHs), have been determined in 100 soil samples collected from a contaminated site centered around a former storehouse in the Kyzyl Kairat village, Almaty region, Kazakhstan, which constitutes an exemplary case example. The OCPs were observed in all analyzed soil samples, with predominance of alpha-HCH, p,p'-DDD, p,p'-DDE, and p,p'-DDT. Total concentrations ranged from 1.38 to 11,100 MUg kg(-1) with an average value of 1040 MUg kg(-1) for DDT and its metabolites and 0.1 to 438 MUg kg(-1) with an average value of 24 MUg kg(-1) for HCHs. The observed concentrations of the OCPs were found to be in agreement with previous studies and are rationalized in terms of the possible degradation pathways of DDTs and HCHs. Spatial distribution patterns of OCPs are elucidated by contour maps. Observed concentrations of the OCPs were used to evaluate the cancer risk to humans via ingestion, dermal contact, and inhalation of soil particles. The cancer risk mainly occurs from ingestion, whereas dermal exposure contributes to a minor extent to the total cancer risk. The risk associated with inhalation was found to be negligible. The total cancer risk for the studied OCPs were found to be p,p'-DDT ? p,p'-DDE ? p,p'-DDD ? alpha-HCH ? beta-HCH ? gamma-HCH. PMID- 27194237 TI - The School Nurse's Role in Addressing Female Genital Mutilation. AB - Female genital mutilation/cutting (FGM/C) is the practice in some immigrant populations of cutting or causing injury to the female genital organs for non medical reasons. The incidence of FGM/C has increased by 314% in school-aged children according to a study published in 2016. The school nurse is in an optimal position to identify children at risk and build collaborative relationships to treat the students affected by the practice. FGM/C is child abuse and carries both federal and state legal consequences. It is important for the school nurse to understand the cultural context, legal guidance, and social consequences of this practice within the greater community. The school nurse should work to develop interagency guidelines to provide safe processes for the child and the family. The most effective programs use a combination of educational strategies for families and communities along with law enforcement to help abolish the practice. PMID- 27194238 TI - Leading Through Lifelong Learning. AB - School nurses, as leaders, are able to exhibit leadership skills through embracing, advocating for, and demonstrating a commitment to lifelong learning. With the continual changes in healthcare and technology, ongoing education is essential to maintain a high standard of expertise and practice. School nurses have many opportunities for continuing education. This article will briefly explore various levels of continuing education, as well as relating ongoing learning to leadership principles. PMID- 27194239 TI - Enhancing Asthma Medication Delivery: Spacers and Valved Holding Chambers. AB - Asthma is one of the most prevalent chronic diseases managed by school nurses, and its management often includes the administration of bronchodilators delivered via a metered dose inhaler (MDI). The use of an MDI requires coordination and mastery of steps that must be performed correctly and in the proper order. These steps are greatly enhanced, especially in the pediatric population, through the use of medical devices-spacers and valved holding chambers. The purpose of this article is to review the rationale and implications for the use of these devices in the school setting. PMID- 27194240 TI - School Nurses' Role in Helping Children With Attention-Deficit/Hyperactivity Disorders. AB - Attention-deficit/hyperactivity disorder (ADHD) is a multifaceted disease characterized by core symptoms of hyperactivity, inattention, and impulsivity, affecting children across every socioeconomic and ethnic group. An estimated 40% to 60% of children with ADHD have comorbidities such as anxiety, depression, and learning disabilities. School nurses must be an integral part of the process of increasing awareness about ADHD through improving the service delivery model for affected children and their families. There is a solid foundation of research on which they can build to improve the benefits through study, workshops, community programs, and national screening programs. PMID- 27194241 TI - Data-Driven Multimodal Sleep Apnea Events Detection : Synchrosquezing Transform Processing and Riemannian Geometry Classification Approaches. AB - A novel multimodal and bio-inspired approach to biomedical signal processing and classification is presented in the paper. This approach allows for an automatic semantic labeling (interpretation) of sleep apnea events based the proposed data driven biomedical signal processing and classification. The presented signal processing and classification methods have been already successfully applied to real-time unimodal brainwaves (EEG only) decoding in brain-computer interfaces developed by the author. In the current project the very encouraging results are obtained using multimodal biomedical (brainwaves and peripheral physiological) signals in a unified processing approach allowing for the automatic semantic data description. The results thus support a hypothesis of the data-driven and bio inspired signal processing approach validity for medical data semantic interpretation based on the sleep apnea events machine-learning-related classification. PMID- 27194242 TI - Community-onset sepsis and its public health burden: a systematic review. AB - BACKGROUND: Sepsis is a life-threatening condition and major contributor to public health and economic burden in the industrialised world. The difficulties in accurate diagnosis lead to great variability in estimates of sepsis incidence. There has been even greater uncertainty regarding the incidence of and risk factors for community-onset sepsis (COS). We systematically reviewed the recent evidence on the incidence and risk factors of COS in high income countries (North America, Australasia, and North/Western Europe). METHODS: Cohort and case-control studies were eligible for inclusion. Medline and Embase databases were searched from 2002 onwards. References of relevant publications were hand-searched. Two reviewers screened titles/abstracts and full-texts independently. One reviewer extracted data and appraised studies which were cross-checked by independent reviewers. Disagreements were resolved via consensus. Odds ratios (ORs) and 95 percent confidence intervals (95 % CIs) were ascertained by type of sepsis (non severe, severe, and septic shock). RESULTS: Ten cohort and 4 case-control studies were included. There was a wide variation in the incidence (# cases per 100,000 per year) of non-severe sepsis (range: 64-514), severe sepsis (range: 40-455), and septic shock (range: 9-31). Heterogeneity precluded statistical pooling. Two cohort and 4 case-control studies reported risk factors for sepsis. In one case control and one cohort study, older age and diabetes were associated with increased risk of sepsis. The same case-control study showed an excess risk for sepsis in participants with clinical conditions (e.g., immunosuppression, lung disease, and peripheral artery disease). In one cohort study, higher risk of sepsis was associated with being a nursing home resident (OR = 2.60, 95 % CI: 1.20, 5.60) and in the other cohort study with being physically inactive (OR = 1.33, 95 % CI: 1.13, 1.56) and smoking tobacco (OR = 1.85, 95 % CI: 1.54, 2.22). The evidence on sex, ethnicity, statin use, and body mass index as risk factors was inconclusive. CONCLUSIONS: The lack of a valid standard approach for defining sepsis makes it difficult to determine the true incidence of COS. Differences in case ascertainment contribute to the variation in incidence of COS. The evidence on COS is limited in terms of the number and quality of studies. This review highlights the urgent need for an accurate and standard method for identifying sepsis. Future studies need to improve the methodological shortcomings of previous research in terms of case definition, identification, and surveillance practice. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015023484. PMID- 27194243 TI - Weak electromagnetic fields alter Ca(2+) handling and protect against hypoxia mediated damage in primary newborn rat myotube cultures. AB - Weak electromagnetic fields (WEF) enhance Ca(2+) entry into cells via voltage gated Ca(2+) channels and affect various aspects of metabolism, structure, and function. However, little information is available on the effect of WEF on skeletal muscle, which depends primarily on intracellular Ca(2+) stores for function and metabolism. Here, we examine the effects of 30 min exposure of rat primary myotube cultures to WEF (1.75 MUT, 16 Hz) on Ca(2+) handling and creatine kinase (CK) release. Free myoplasmic Ca(2+) concentration ([Ca(2+) i]) was measured with the ratiometric dye indo-1. WEF did not affect basal [Ca(2+)]i but decreased the twitch [Ca(2+)]i transient in a time-dependent manner, and the twitch amplitude was decreased to ~30 % after 30 min. WEF completely abolished the increase in [Ca(2+)]i induced by potassium chloride (~60 mM) but had no effect on the increase induced by caffeine (~6 mM). Hypoxia (2 h exposure to 100 % argon) resulted in a marked loss of CK into the medium (400 % of normoxic value), as well as a rapid (within 20 min) and sustained increase in basal [Ca(2+)]i (~20 % above baseline). However, during exposure to WEF, basal [Ca(2+)]i remained constant during the initial 60 min of hypoxia and, thereafter, increased to levels similar to those observed in the absence of WEF. Finally, WEF blocked about 80 % of hypoxia-mediated CK release (P < 0.05). These data demonstrate that WEF inhibits increases in [Ca(2+)]i by interfering with muscle excitation and protects against muscle damage induced by hypoxia. Thus, WEF may have therapeutic/protective effects on skeletal muscle. PMID- 27194244 TI - Toxic and adjuvant effects of silica nanoparticles on ovalbumin-induced allergic airway inflammation in mice. AB - BACKGROUND: Silica nanoparticles (SNPs) can easily enter in respiratory system via inhalation because of their low molecular weight and ease of dispersion. Toxicity and adverse effects of SNPs vary according to the physical characteristics of the particle. METHODS: To evaluate the toxic and adjuvant effects of 3 types of SNPs in the airway system, six-week-old female BALB/c mice were intranasally administered 3 types of SNPs (spherical [S-SNP], mesoporous [M SNP], and polyethylene glycol-conjugated [P-SNP]) alone or SNPs/ovalbumin (OVA), three times weekly for 2 weeks. Airway hyper-responsiveness (AHR), bronchoalveolar lavage fluid (BALF), cytokine levels, and histology of the lungs were analyzed. RESULTS: The S-SNPs/OVA group and M-SNPs/OVA group showed significant AHR, compared to the control group. Among all SNP-treated groups, the group administered SNPs/OVA showed greater inflammatory cell infiltration in BALF, extensive pathological changes, and higher cytokine levels (IL-5, IL-13, IL 1beta, and IFN-gamma) than those administered SNPs alone or saline/OVA. CONCLUSION: Exposure to SNPs alone and SNPs/OVA induced toxicity in the respiratory system. SNPs alone showed significant toxic effects on the airway system. Meanwhile, SNPs/OVA exerted adjuvant effects to OVA of inducing allergic airway inflammation. In particular, M-SNPs showed the most severe airway inflammation in both direct toxicity and adjuvant effect assays. P-SNPs induced less inflammation than the other types of SNPs in both models. PMID- 27194245 TI - Grey Matter Density Predicts the Improvement of Naming Abilities After tDCS Intervention in Agrammatic Variant of Primary Progressive Aphasia. AB - Agrammatic variant primary progressive aphasia is a neurodegenerative disorder specifically characterized by language deficits. A recent study has demonstrated a beneficial effect of transcranial direct current stimulation (tDCS) in combination with language training on naming accuracy in these patients. The aim of the study was to evaluate whether the improvement of naming accuracy after tDCS during language training was related to regional grey matter (GM) density. Eighteen avPPA patients underwent a brain magnetic resonance imaging before receiving a treatment that consisted of tDCS over the left dorsolateral prefrontal cortex during individualized language training (10 daily therapy sessions, 5 days per week from Monday to Friday). Performances on neuropsychological tests and naming of objects (treated and untreated) and actions were assessed at baseline, post-treatment and 3 months after treatment. Correlations between individual changes after treatment on neuropsychological tests and on picture naming task and voxel-based GM volume at baseline were performed. We found that the improvement in the naming of treated objects was positively correlated with GM volume in the left fusiform, left middle temporal, and right inferior temporal gyri whereas action naming change was related to GM density in the left middle temporal gyrus. In conclusion baseline density of GM in these brain regions was associated with greater treatment response on naming performances, suggesting that intervention in early disease stages might be most successful. These findings have implication for designing future rehabilitation protocols in language variants of frontotemporal dementia. PMID- 27194246 TI - Erratum to: A multifunctional therapeutic approach to disease modification in multiple familial mouse models and a novel sporadic model of Alzheimer's disease. PMID- 27194247 TI - Effects of mammalian target of rapamycin inhibitors on cytokine production and differentiation in keratinocytes. AB - Risk factors for the development of cutaneous squamous cell carcinoma (cSCC) include ultraviolet radiation and immunosuppression. In particular, solid organ transplant recipients show a high incidence of cSCC, depending on the immunosuppressive regimen. While azathioprine or calcineurin inhibitors increase the risk of cSCC development, mammalian target of rapamycin (mTOR) inhibitors decreases this risk. At the moment, the mechanisms behind this protective effect of mTOR inhibitors are not fully understood. We evaluated effects of the mTOR inhibitors sirolimus and everolimus on keratinocytes, cSCC cell lines and an organotypic skin model in vitro in regard to proliferation, cytokine secretion and differentiation. We show that mTOR inhibitors block keratinocyte proliferation and alter cytokine and cytokeratin production: in particular, mTOR inhibition leads to upregulation of interleukin-6 and downregulation of cytokeratin 10. Therefore, mTOR inhibitors have effects on keratinocytes, which could play a role in the pathogenesis of cSCC. PMID- 27194248 TI - Thinking outside the box: re-evaluating the approach to penetrating cardiac injuries. AB - INTRODUCTION: Penetrating cardiac injuries are infrequent but highly lethal. To address these injuries, cardiopulmonary bypass and cardiothoracic surgery availability are required for Level I trauma center verification. However, acute care surgeons are more readily available for this time-sensitive injury. The purpose of this study was to review an acute care surgery-based experience with penetrating cardiac trauma at an urban Level 1 trauma center. Our hypothesis was that care provided solely by acute care surgeons was both safe and effective for this patient population. METHODS: All patients with injuries to the 'cardiac box' following penetrating thoracic trauma were identified from 2005-2010. Demographic and injury related data were obtained. The types and location of cardiac injury, as well as patient outcomes, were determined from operative reports. RESULTS: 1701 patients with penetrating chest trauma were admitted during the study period. 260 patients were identified as having high-risk injuries and were included in the review. 37 patients underwent resuscitative thoracotomy, with a survival rate of 8 %. 76 patients (29 %) suffered a cardiac injury. 72 % of these patients had a preoperative FAST exam, which had a sensitivity and specificity of 56.5 and 82.5 % respectively. 82 % underwent a pericardial window, which had a positive predictive value of 81.4 %. 61 % (n = 46) of the patients with a cardiac injury survived, while the overall death rate in this cohort was 21 %. No patients in the cohort required cardiopulmonary bypass for emergent repair of cardiac injury and acute care surgeons performed all cases. CONCLUSION: Penetrating injury to the heart is highly lethal and time-sensitive. Increasingly, FAST and subxyphoid pericardial window are relied upon to make the diagnosis in patients arriving in varying stages of shock to the resuscitation room. Acute care surgeons are the most appropriate surgeons to care for these injuries and provide safe and effective care. PMID- 27194249 TI - Effects of hyaluronic acid and tacrolimus on the prevention of perineural scar formation and on nerve regeneration after sciatic nerve repair in a rabbit model. AB - PURPOSE: Scar formation after injured peripheral nerve repair is a significant clinical problem because it prevents nerve regeneration. The aim of this study was to investigate and compare the effects of hyaluronic acid (HA) and tacrolimus (FK506) on peripheral nerve regeneration in rabbits after the drugs were topically applied at the site of nerve repair. METHODS: Thirty adult male European rabbits (Oryctolagus cuniculus), ranging in weight from 2.5 to 3 kg, were randomly assigned to three groups: the HA and FK506 groups comprised the experimental groups, while the saline group served as the control. At week 12, macroscopic and microscopic evaluations were performed and analyzed. RESULTS: In general, the macroscopic evaluations (skin and muscle fascia closure and nerve adherence), microscopic evaluations (cellular components, scar tissue formation index, and histomorphological organization), and measurements of nerve diameter and gastrocnemius muscle wet weight demonstrated the positive effects of topical application of these pharmacological agents (HA and FK506); HA and FK506 prevented scar formation and enhanced nerve regeneration. No significant differences in the parameters described above were observed between the HA and FK506 groups (P > 0.05). However, significant differences were observed between both the HA and FK506 groups and the saline group (P < 0.05). CONCLUSION: Based on our findings, topical application of HA and FK506 exhibits equally positive effects, preventing perineural scar formation and enhancing nerve regeneration after peripheral nerve repair. PMID- 27194250 TI - Distribution of Nitrate in Different Aquifers in the Urban District of Zhanjiang, China. AB - The study of NO3 (-) contamination in groundwater is becoming increasingly significant as high concentrations of NO3 (-) in groundwater can do damage to public health. Nitrate pollution in the shallow, middle-deep and deep aquifers in the urban district of Zhanjiang was studied using the ordinary Kriging interpolation method combined with hydrochemical and correlation analyses in 2011. The results showed NO3 (-) pollution was present in the shallow groundwater, with average concentrations of 47.43 mg/L and standard deviation of 50.92. Nitrate concentrations were lower in middle-deep and deep aquifers, with average concentrations of 2.36, 0.80 mg/L, and standard deviation of 6.23, 0.93, respectively. Nitrate was correlated with Na(+) + K(+), Mg(2+), Cl(-) and SO4 (2 ) in the shallow aquifer, and the spatial distributions of NO3 (-) exhibited a same pattern with TDS in the shallow aquifer, the NO3 (-) pollution in the middle deep and deep aquifers is less serious. PMID- 27194252 TI - Changing the Publication Culture From "Nice to Do" to "Need to Do": Implications for Nurse Leaders in Acute Care Settings. AB - PROBLEM: Nurses in clinical settings often generate innovative practice ideas to inform their practice and improve patient outcomes. Yet, few publish and share these innovations with a wider audience. Barriers impeding clinical nurses from writing for publication include discomfort with writing, lack of time, and scarce resources. METHODS: A qualitative study was designed to determine obstacles and facilitators to writing for publication. Interviews were conducted with five clinical nurses who had recently published in peer-reviewed journals. FINDINGS: Three themes emerged from the data: culture of "nice to do," personal motivation, and writing experiences. Findings from the study offer implications for nurse leaders to help increase publication efforts by clinical nurses in acute care settings. CONCLUSION: Nurse leaders can promote publication by clinical nurses through three main strategies: create a culture that supports publication, offer incentives to motivate nurses to publish and reward those who do publish, and provide writing experiences that facilitate writing for publication. PMID- 27194251 TI - The Effects of Cadmium Exposure on Fitness-Related Traits and Antioxidant Responses in the Wolf Spider, Pardosa pseudoannulata. AB - The objective of the present study was to assess the ecotoxicological responses of Pardosa pseudoannulata to a common environmental pollutant, cadmium. Third instar spiderlings and adult spiders were exposed to sublethal concentrations of CdCl2 solution in their drinking water. The Cd content in P. pseudoannulata adults increased significantly with the number of days of exposure to a 0.2 mM CdCl2 solution, when exposed to 2 mM CdCl2 solution, the Cd content in the spiders increased sharply in the first two (male) or three (female) weeks, and then no significant changes were recorded following with the next three (male) or two (female) weeks exposure. Exposure of spiders to Cd contaminated drinking water resulted in reduced body mass, delayed development, fewer eggs and increased mortality. Significantly higher activities of superoxide dismutase, catalase and glutathione-S-transferase were recorded in the spiders after 7 day exposure to 0.2 mM CdCl2 solution. However, longer-term exposures or increased Cd concentrations did not result in significantly higher antioxidant enzyme activity relative to control treatment. PMID- 27194253 TI - Clinical benefits and oncologic equivalence of self-expandable metallic stent insertion for right-sided malignant colonic obstruction. AB - BACKGROUND: The efficacy of stenting for right-sided malignant colonic obstruction is unknown. This study aimed to evaluate the safety, feasibility, and clinical benefits of self-expandable metallic stent insertion for right-sided malignant colonic obstruction. METHODS: Clinical data from patients who underwent right hemicolectomy for right colon cancer from January 2006 to July 2014 at three Korea University hospitals were retrospectively reviewed. A total of 39 patients who developed malignant obstruction in the right-sided colon were identified, and their data were analyzed. RESULTS: Stent insertion was attempted in 16 patients, and initial technical success was achieved in 14 patients (87.5 %). No stent-related immediate complications were reported. Complete relief from obstruction was achieved in all 14 patients. Twenty-five patients, including two patients who failed stenting, underwent emergency surgery. In the stent group, 93 % (13/14) of patients underwent elective laparoscopic surgery, and only one surgery was converted to an open procedure. All patients in the emergency group underwent emergency surgery within 24 h of admission. In the emergency group, only 12 % (3/25) of patients underwent laparoscopic surgery, with one surgery converted to an open procedure. All patients in both groups underwent either laparoscopy-assisted or open right/extended right hemicolectomy with primary anastomoses as the first operation. The operative times, retrieved lymph nodes, and pathologic stage did not differ between the two groups. Postoperative hospital stay (9.4 +/- 3.4 days in the stent group vs. 12.4 +/- 5.9 in the emergency group, p = 0.089) and time to resume oral food intake (3.2 +/- 2.1 days in the stent group vs. 5.7 +/- 3.4 in the emergency group, p = 0.019) were shorter in the stent group. And there were no significant differences in disease free survival and overall survival between the two groups. CONCLUSIONS: Stent insertion appears to be safe and feasible in patients with right-sided colonic malignant obstruction. It facilitates minimally invasive surgery and may result in better short-term surgical outcomes. PMID- 27194254 TI - The learning curve of laparoendoscopic single-site adrenalectomy: an analysis of over 100 cases. AB - BACKGROUND: Recently, laparoendoscopic single-site adrenalectomy (LESS-A) has been developed as an alternative treatment for adrenal tumors. Although LESS-A is more technically complex than conventional laparoscopic adrenalectomy, its learning curve and the factors associated with poor surgical outcomes are poorly understood. We analyzed the learning curve of LESS-A and attempted to identify risk factors associated with worse surgical outcomes. METHODS: We identified 103 patients who underwent LESS-A [performed by the same surgeon (A.M.)] from 2009 to 2015. The learning curve was analyzed using the moving average method (the 10 case moving average), and we assessed potential risk factors for a prolonged pneumoperitoneum time. RESULTS: The learning curve stabilized at 30 cases. The cases were divided into two groups, the learning stage (LS) (cases 1-29) and master stage (MS) (cases 30-103) groups. The percentage of females and the frequency of previous abdominal surgery were higher in the LS group (p = 0.022 and 0.001, respectively). In the LS group, the mean pneumoperitoneum time was 92 +/- 35 min, which was significantly longer than the equivalent value for the MS group (55 +/- 18 min, p < 0.001). In the LS group, univariate analysis revealed that tumor size (>=50 mm) and the visceral fat area (VFA)/total fat area (TFA) ratio (>=0.49) were significantly associated with a prolonged pneumoperitoneum time (p = 0.046 and 0.046, respectively). In the multivariate analysis, tumor size and the VFA/TFA ratio were confirmed to be associated with a prolonged pneumoperitoneum time (p = 0.029 and 0.029, odds ratio 20.83 and 20.83, respectively). On the other hand, none of the examined factors were found to be associated with a prolonged pneumoperitoneum time in the MS group. CONCLUSIONS: LESS-A was performed safely in most cases. However, surgeons who are learning the LESS-A procedure need to pay attention to tumor size and visceral obesity. PMID- 27194255 TI - Robotic radical resection for hilar cholangiocarcinoma: perioperative and long term outcomes of an initial series. AB - BACKGROUND: Radical resection for hilar cholangiocarcinoma (HCa) is one of the most challenging abdominal procedures. Robotic-assisted approach is gaining popularity in hepatobiliary surgery but scarcely tried in the management of HCa. We herein report our initial experience of robotic radical resection for HCa. METHODS: Between May 2009 and October 2012, 10 patients underwent fully robotic assisted radical resection for HCa in a single institute. The perioperative and long-term outcomes were analyzed and compared with a contemporaneous 32 patients undergoing traditional open surgery. RESULTS: The 10 patients presented one of Bismuth-Corlette type II, four of IIIa, one of IIIb and four of IV. There was no significant clinicopathological disparity between the robotic and open groups. The robotic radical resection involves hemihepatectomy plus caudate lobectomy or trisectionectomy, extrahepatic bile duct resection, radical lymphadenectomy and Roux-en-Y hepaticojejunostomy. No conversion to laparotomy occurred. Robotic resection compared unfavorably to traditional open resection in operative time (703 +/- 62 vs. 475 +/- 121 min, p < 0.001) and morbidity [90 (9/10) vs. 50 %, p = 0.031]. No significant difference was found in blood loss, mortality and postoperative hospital stay. Major complications (>=Clavien-Dindo III) occurred in three patients of robotic group. One patient died of posthepatectomy liver failure on postoperative day 18. The hospital expenditure was much higher in robotic group (USD 27,427 +/- 21,316 vs. 15,282 +/- 5957, p = 0.018). The tumor recurrence-free survival was inferior in robotic group (p = 0.029). CONCLUSIONS: Fully robotic-assisted radical resection for HCa is technically achievable in experienced hands and should be limited to highly selective patients. Our current results do not support continued practice of robotic surgery for HCa, until significant technical and instrumental refinements are demonstrated. PMID- 27194256 TI - Preclinical safety testing for morcellation and extraction for an endobag with sealable ports: in vitro pilot study. AB - BACKGROUND: Electromechanical power morcellation is an important tool of modern laparoscopy. Recent reports on the spread of previously undetected malignancy by power morcellation indicate the need for additional protective devices to reduce this risk. We conducted a study to obtain the first data concerning the safety of an endobag with three closable ports during morcellation and subsequent bag extraction under in vitro conditions, mimicking the settings in our operating theater. The second purpose of the study was to establish a minimal width of the skin incision necessary to safely extract the sealed bag after morcellation. METHODS: The morcellation test was carried out on 11 stained porcine muscle tissue samples with one additional sample as a control. The insufflation pressure was set at 12 mmHg. After filling the endobag with blue dye solution, an additional extraction test was conducted by pulling the closed bag through a template with apertures of various diameters. For each opening, a series of ten bag extractions was carried out. RESULTS: No loss of solid material or fluid was recorded during the morcellation test. The extraction test showed a loss of fluid for template openings smaller than 18 mm. The force necessary to extract the bag was inversely related to the width of the aperture. CONCLUSIONS: The data suggest that under the evaluated conditions, the use of a closable morcellation bag can considerably improve the patient's safety during morcellation. Further studies are necessary to evaluate the influence of the bag on operating time, intervention costs and complications. PMID- 27194258 TI - Consistency of patient-reported outcomes after cholecystectomy and their implications on current surgical practice: a prospective multicenter cohort study. AB - BACKGROUND: Persistent postoperative pain (up to 41 %) and significant practice variation necessitate better patient selection for cholecystectomy. Patient reported outcome measures (PROMs) are nowadays known to serve as a tool for better patient selection, although variability within these subjective outcomes may be a point for debate. This study determines associations of both the preoperative pain and patient characteristics with PROMs at 24 weeks after cholecystectomy. In order to evaluate variability of PROMs, we also determined consistency of these outcomes in time. METHODS: This prospective multicenter cohort study included adult patients diagnosed with uncomplicated symptomatic cholecystolithiasis. Twenty-four weeks after surgery, a questionnaire study was carried out, containing Gastrointestinal Quality of Life Index (GIQLI) and Patients' Experience of Surgery Questionnaire. Results were compared to preoperative data and results 12 weeks post-cholecystectomy. Logistic regression analyses were performed to determine associations. Additional post hoc analysis on associations between preoperative selection criteria and PROMs was done. RESULTS: A total of 360 patients (85 %) responded. Postoperative absence of pain was reported by 59.2 %. Associated characteristics were symptoms <=1 year prior to surgery [OR 1.85 (95 % CI 1.11-3.09)] and high baseline GIQLI score [OR 1.04 (95 % CI 1.02-1.05)]. General improvement in abdominal symptoms and positive result of surgery were found in 90 %; no preoperative variables were significantly associated. PROMs showed consistency at 12 and 24 weeks postoperatively. Post hoc analysis showed no significant associations. CONCLUSION: PROM-based preoperative selection criteria need to be considered to select those patients who achieve freedom of pain after surgical treatment of uncomplicated symptomatic cholecystolithiasis. Other patients might consider cholecystectomy as successful, but are less likely to be free of pain. Usefulness of PROMs is underscored as they proved to be consistent in time in evaluating surgical outcome. PMID- 27194259 TI - Domestically produced Chinese minimally invasive surgical robot system "Micro Hand S" is applied to clinical surgery preliminarily in China. AB - OBJECTIVE: To develop and validate one low-cost and easy-use domestically produced Chinese minimally invasive surgical robot system "Micro Hand S" that surgeons can use to resolve the complicated surgeries challenge. METHODS: From April 2014 to April 2015, one patient with gastric perforation, three patients with acute appendicitis, five patients with acute cholecystitis, and one patient with right colon cancer underwent robotic-assisted surgeries. Eight of these patients were followed for 1 month, and pre- and postoperative changes in blood route test and hepatorenal function examination, surgery duration, hospital stay, total robotic setup time, total robotic operation time, intraoperative blood loss, total postoperative drainage amount, duration of bearing drainage tubes were recorded. Two patients withdrew from the study because of individual privacies. RESULTS: We accomplished surgical procedures using "Micro Hand S." No intraoperative complications or technical problems were encountered. All patients recovered and discharged from hospital without complications. CONCLUSIONS: The domestic surgical robot system "Micro Hand S" was validated as safe and effective through these clinical cases. The proposed design method is an effective way to make "Micro Hand S" become low-cost and easy-use robot system. PMID- 27194257 TI - Surgical cure for type 2 diabetes by foregut or hindgut operations: a myth or reality? A systematic review. AB - BACKGROUND: Bariatric surgery results in remission of type 2 diabetes mellitus in a significant proportion of patients. Animal research has proposed the foregut and hindgut hypotheses as possible mechanisms of remission of T2DM independent of weight loss. These hypotheses have formed the basis of investigational procedures designed to treat T2DM in non-obese (in addition to obese) patients. The aim of this study was to review the procedures that utilise the foregut and hindgut hypotheses to treat T2DM in humans. METHODS: A systematic review was conducted to identify the investigational procedures performed in humans that are based on the foregut and hindgut hypotheses and then to assess their outcomes. RESULTS: Twenty four studies reported novel procedures to treat T2DM in humans; only ten utilised glycated haemoglobin A1c (HbA1c) in their definition of remission. Reported remission rates were 20-40 % for duodenal-jejunal bypass (DJB), 73-93 % for duodenal-jejunal bypass with sleeve gastrectomy (DJB-SG), 62.5-100 % for duodenal jejunal bypass sleeve (DJBS) and 47-95.7 % for ileal interposition with sleeve gastrectomy (II-SG). When using a predetermined level of HbA1c to define remission, the remission rates were lower (27, 63, 0 and 65 %) for DJB, DJB-SG, DJBS and II-SG. CONCLUSIONS: The outcomes of the foregut- and hindgut-based procedures are not better than the outcomes of just one of their components, namely sleeve gastrectomy. The complexity of these procedures in addition to their comparable outcomes to a simpler operation questions their utility. PMID- 27194260 TI - Comparison of clinical outcome of laparoscopic versus open appendectomy for complicated appendicitis. AB - BACKGROUND: Laparoscopic appendectomy is now the treatment of choice in uncomplicated appendicitis. To date its importance in the treatment of complicated appendicitis is not clearly defined. METHODS: From January 2005 to June 2013 a total of 1762 patients underwent appendectomy for the suspected diagnosis of appendicitis at our institution. Of these patients 1516 suffered from complicated appendicitis and were enrolled. In total 926 (61 %) underwent open appendectomy (OA) and 590 (39 %) underwent laparoscopic appendectomy (LA). The following parameters were retrospectively analyzed: age, sex, operative times, histology, length of hospital stay, 30-day morbidity focusing on occurrence of surgical site infections, intraabdominal abscess formation, postoperative ileus and appendiceal stump insufficiency, conversion rate, use of endoloops and endostapler. RESULTS: A statistically significant difference in operative time was observed between the laparoscopic and the open group (64.5 vs. 60 min; p = 0.002). Median length of hospitalization was significantly shorter in the laparoscopic group (p < 0.000). Surgical site infections occurred exclusively after OA (38 vs. 0 patients). Intraabdominal abscess formation occurred statistically significantly more often after LA (2 vs. 10 patients; p = 0.002). There were no statistical significances concerning the occurrence of postoperative ileus (p = 0.261) or appendiceal stump insufficiencies (p = 0.076). CONCLUSIONS: The laparoscopic approach for complicated appendicitis is a safe and feasible procedure. Surgeons should be aware of a potentially higher incidence of intraabdominal abscess formation following LA. Use of endobags , inversion of the appendiceal stump and carefully conducted local irrigation of the abdomen in a supine position may reduce the incidence of abscess formation. PMID- 27194262 TI - Current training on the basics of robotic surgery in the Netherlands: Time for a multidisciplinary approach? AB - INTRODUCTION: The following research questions were answered: (1) What are the training pathways followed by the current robot professionals? (2) Are there any differences between the surgical specialties in robot training and robot use? (3) What is their opinion about multidisciplinary basic skills training? METHODS: An online questionnaire was sent to 91 robot professionals in The Netherlands. The questionnaire contained 21 multiple-choice questions focusing on demographics, received robot training, and their opinion on basic skills training in robotic surgery. RESULTS: The response rate was 62 % (n = 56): 13 general surgeons, 16 gynecologists, and 27 urologists. The urologists performed significantly more robotic procedures than surgeons and gynecologists. The kind of training of all professionals varied from a training program by Intuitive Surgical, master apprenticeship with or without duo console, fellowship, and self-designed training programs. The training did neither differ significantly among the different specialties nor the year of starting robotic surgery. Majority of respondents favor an obliged training program including an examination for the basics of robot skills training. CONCLUSION: Training of the current robot professionals is mostly dependent on local circumstances and the manufacturer of the robot system. Training is independent of the year of start with robotic surgery and speciality. To guarantee the quality of future training of residents and fellows in robot-assisted surgery, clear training goals should be formulated and implemented. Since this study shows that current training of different specialities does not differ, training in robotic surgery could be started by a multidisciplinary basic skills training and assessment. PMID- 27194263 TI - Improving training of laparoscopic tissue manipulation skills using various visual force feedback types. AB - BACKGROUND: Visual force feedback allows trainees to learn laparoscopic tissue manipulation skills. The aim of this experimental study was to find the most efficient visual force feedback method to acquire these skills. Retention and transfer validity to an untrained task were assessed. METHODS: Medical students without prior experience in laparoscopy were randomized in three groups: Constant Force Feedback (CFF) (N = 17), Bandwidth Force Feedback (BFF) (N = 16) and Fade in Force Feedback (N = 18). All participants performed a pretest, training, post test and follow-up test. The study involved two dissimilar tissue manipulation tasks, one for training and one to assess transferability. Participants performed six trials of the training task. A force platform was used to record several force parameters. RESULTS: A paired-sample t test showed overall lower force parameter outcomes in the post-test compared to the pretest (p < .001). A week later, the force parameter outcomes were still significantly lower than found in the pretest (p < .005). Participants also performed the transfer task in the post test (p < .02) and follow-up (p < .05) test with lower force parameter outcomes compared to the pretest. A one-way MANOVA indicated that in the post-test the CFF group applied 50 % less Mean Absolute Nonzero Force (p = .005) than the BFF group. CONCLUSION: All visual force feedback methods showed to be effective in decreasing tissue manipulation force as no major differences were found between groups in the post and follow-up trials. The BFF method is preferred for it respects individual progress and minimizes distraction. PMID- 27194261 TI - The presence of rapid on-site evaluation did not increase the adequacy and diagnostic accuracy of endoscopic ultrasound-guided tissue acquisition of solid pancreatic lesions with core needle. AB - BACKGROUND: Rapid on-site evaluation (ROSE) improves the adequacy and accuracy of EUS-guided tissue acquisition, although it is not routinely widely available. Evidence suggested that core needles might overcome the absence of ROSE. The aim of this study was to evaluate the influence of ROSE on the adequacy and accuracy of EUS-guided tissue acquisition with core needles in patients with pancreatic solid lesions. METHODS: Patients who underwent EUS-guided tissue acquisition of pancreatic mass lesions were retrospectively identified at three tertiary referral centers and those performed with the core needle were included. Adequacy, defined as the rate of cases in which a tissue specimen for proper examination was achieved, with and without ROSE was the primary outcome measure. The diagnostic accuracy and tissue core acquisition were the secondary outcome measures. RESULTS: A total of 333 patients with pancreatic solid mass lesions were included in the study; 140 cases sampled with ROSE and 193 cases without ROSE. The adequacy was 92.1 % in the group sampled with ROSE and 88.1 % in the group without ROSE (p = 0.227). In the ROSE group sensitivity, specificity, and accuracy were 90.7, 100 and 92.1 %, respectively. In the group without ROSE, sensitivity, specificity, and accuracy were 87.2, 100, and 88.1 %, respectively. No difference for all these figures was observed between the two groups. The tissue core was available in 61.4 and 53.4 % of cases with and without ROSE, respectively (p = 0.143). CONCLUSION: In the absence of ROSE, EUS-based tissue acquisition with Core needle should be considered since it achieves comparable tissue sampling adequacy and accuracy. PMID- 27194264 TI - Robotic surgery: current perceptions and the clinical evidence. AB - BACKGROUND: It appears that a discrepancy exists between the perception of robotic-assisted surgery (RAS) and the current clinical evidence regarding robotic-assisted surgery among patients, healthcare providers, and hospital administrators. The purpose of this study was to assess whether or not such a discrepancy exists. METHODS: We administered survey questionnaires via face-to face interviews with surgical patients (n = 101), healthcare providers (n = 58), and senior members of hospital administration (n = 6) at a community hospital that performs robotic surgery. The respondents were asked about their perception regarding the infection rate, operative time, operative blood loss, incision size, cost, length of hospital stay (LOS), risk of complications, precision and accuracy, tactile sensation, and technique of robotic-assisted surgery as compared with conventional laparoscopic surgery. We then performed a comprehensive literature review to assess whether or not these perceptions could be corroborated with clinical evidence. RESULTS: The majority of survey respondents perceived RAS as modality to decrease infection rate, increase operative time, decrease operative blood loss, smaller incision size, a shorter LOS, and a lower risk of complications, while increasing the cost. Respondents also believed that robotic surgery provides greater precision, accuracy, and tactile sensation, while improving intra-operative access to organs. A comprehensive literature review found little-to-no clinical evidence that supported the respondent's favorable perceptions of robotic surgery except for the increased costs, and precision and accuracy of the robotic-assisted technique. CONCLUSIONS: There is a discrepancy between the perceptions of robotic surgery and the clinical evidence among patients, healthcare providers, and hospital administrators surveyed. PMID- 27194265 TI - Open versus laparoscopic unilateral inguinal hernia repairs: defining the ideal BMI to reduce complications. AB - OBJECTIVES: Open inguinal hernia repair is felt to be a less expensive operation than a laparoscopic one. Performing open repair on patients with an obese body mass index (BMI) results in longer operative times, longer hospital stay, and complications that will potentially impose higher cost to the facility and patient. This study aims to define the ideal BMI at which a laparoscopic inguinal hernia repair will be advantageous over open inguinal hernia repair. METHODS: The NSQIP database was analyzed for (n = 64,501) complications, mortality, and operating time for open and laparoscopic inguinal hernia repairs during the time period from 2005 to 2012. Bilateral and recurrent hernias were excluded. Chi square tests and Fisher's exact tests were used to assess associations between type of surgery and categorical variables including demographics, risk factors, and 30-day outcomes. Multivariable regression analyses were performed to determine whether odds ratios differed by level of BMI. The HCUP database was used for determining difference in cost and length of stay between open and laparoscopic procedures. RESULTS: There were 17,919 laparoscopic repairs and 46,582 open repairs in the study period. The overall morbidity (across all BMI categories) is statistically greater in the open repair group when compared to the laparoscopic group (p = 0.03). Postoperative complications (including wound disruption, failure to wean from the ventilator, and UTI) were greater in the open repair group across all BMI categories. Deep incisional surgical site infections (SSI) were more common in the overweight open repair group (p = 0.026). The return to the operating room across all BMI categories was statistically significant for the open repair group (n = 269) compared to the laparoscopic repair group (n = 70) with p = 0.003. There was no difference in the return to operating room between the BMI categories. The odds ratio (OR) was found to be statistically significant when comparing the obese category to both normal and overweight populations for the open procedure. CONCLUSION: Open hernia repairs have more complications than do laparoscopic ones; however, there does not appear to be a difference in treating obese patients with hernias using a laparoscopic approach versus an open one. One may consider using a laparoscopic approach in overweight patients (BMI 25-29.9) as there appears to be fewer deep SSI. PMID- 27194268 TI - [In Process Citation]. PMID- 27194267 TI - Tissue diagnosis of GI subepithelial tumor only through Trucut biopsy under a forward-viewing endoscope: applicability as newer diagnostic modality. AB - BACKGROUND: Trucut biopsy (TCB) has been proposed to overcome the limitations of endoscopic ultrasonography (EUS)-guided fine-needle aspiration for the pathologic diagnosis of upper gastrointestinal (GI) subepithelial tumor (SET); however, it can be difficult to perform because the Trucut biopsy needle is very stiff. Although technical failures have been reported with the use of TCB, recently the forward-viewing echoendoscope showed a high diagnostic accuracy. We hypothesized that TCB under a conventional forward-viewing endoscope can be applied with higher yield of tissue diagnosis. METHODS: To evaluate the feasibility of TCB under a forward-looking endoscopy without cumbersome EUS guidance, we introduced a 19-gauge TCB needle into the working channel of a conventional upper endoscope in 27 patients with GI SET to make tissue diagnosis. Prospectively collected data were analyzed, including technical success rate, pathologic result, and adverse events. RESULTS: Twenty-seven patients with GI SET (18 esophageal tumors and nine gastric tumors) underwent TCB under a forward-looking endoscope. All procedures were performed safely without any TCB-related complications. Subsequently, histopathology examination revealed gastrointestinal stromal tumors (GISTs) in three cases and leiomyomas in 21 cases. Histologic assessment was completed in 24 out of 27 patients (88.9 %) because tissue obtained from three patients, whose tumors were located in the stomach, was not sufficient for the pathologic diagnosis. CONCLUSIONS: TCB using a conventional forward-viewing endoscope without EUS guidance provided an excellent pathologic diagnosis of upper GI SET. PMID- 27194266 TI - A systematic review of low-cost laparoscopic simulators. AB - BACKGROUND: Opportunities for surgical skills practice using high-fidelity simulation in the workplace are limited due to cost, time and geographical constraints, and accessibility to junior trainees. An alternative is needed to practise laparoscopic skills at home. Our objective was to undertake a systematic review of low-cost laparoscopic simulators. METHOD: A systematic review was undertaken according to PRISMA guidelines. MEDLINE/EMBASE was searched for articles between 1990 and 2014. We included articles describing portable and low cost laparoscopic simulators that were ready-made or suitable for assembly; articles not in English, with inadequate descriptions of the simulator, and costs >L1500 were excluded. Validation, equipment needed, cost, and ease of assembly were examined. RESULTS: Seventy-three unique simulators were identified (60 non commercial, 13 commercial); 55 % (33) of non-commercial trainers were subject to at least one type of validation compared with 92 % (12) of commercial trainers. Commercial simulators had better face validation compared with non-commercial. The cost ranged from L3 to L216 for non-commercial and L60 to L1007 for commercial simulators. Key components of simulator construction were identified as abdominal cavity and wall, port site, light source, visualisation, and camera monitor. Laptop computers were prerequisite where direct vision was not used. Non commercial models commonly utilised retail off-the-shelf components, which allowed reduction in costs and greater ease of construction. CONCLUSION: The models described provide simple and affordable options for self-assembly, although a significant proportion have not been subject to any validation. Portable simulators may be the most equitable solution to allow regular basic skills practice (e.g. suturing, knot-tying) for junior surgical trainees. PMID- 27194270 TI - A SPECIAL LEARNING EXPERIENCE ABOUT TRANSFERENCE AND COUNTERTRANSFERENCE DYNAMICS AT THE BEGINNING OF MY PSYCHOANALYTIC TRAINING(.). AB - Drawing upon his description of the early phases of the analysis of the second case of official supervision, the author illustrates in his work why this experience became a foundational moment in his formative trajectory as a psychoanalyst. Three important aspects are discussed: (1) the significant role his supervisor played in helping to manage and to confront the difficult dynamics of transference and countertransference that characterized the author's early years of analytic work with patients; (2) the transformative factors that opened up new avenues in the repetition and the original traumatic pathology put forward at great length by the patient; and (3) the making contact for the first time with that area of inter/intrapsychic phenomena that the author has since then explored widely and theorized about, under the name of relational dynamics governed by role-reversal. PMID- 27194271 TI - WARMED BY THE FIRES OF THE UNCONSCIOUS OR BURNED TO A CRISP. AB - In this paper I talk about the relationship or link between unconscious and conscious material. When the link is optimal we are warmed by the fires of the unconscious so that what we say and do has meaning-it is alive. When the link between conscious and unconscious is too close we are in danger of being burned to a crisp. The present is the past and the world of consensual reality pales in comparison to the emotionally charged unconscious fantasy pressing for discharge. An extended case vignette is used to illustrate the links between past and present as they unfold in a patient's life and between analyst and patient. PMID- 27194272 TI - THE ROLE OF AN IMMIGRANT MOTHER IN HER ADOLESCENT'S IDENTITY FORMATION: "WHO AM I?". AB - Immigration is a complex bio-psycho-social process and the immigrant mother has a truly complex task in lending her ego strength to her adolescent offspring. The normal adolescence's decathexis of the love object and the consequent search for a new object may not happen smoothly for those adolescents whose mothers are immigrants. The immigration experience may cause the immigrant mother, who lost her motherland, deeper disturbance in self-identity as well as disequilibrium in her psychic structure, which in turn impacts adversely her adolescent's development. The adolescent's inadequate early experience with an immigrant mother may result in a deeper disturbance in his separation-individuation process as well as his identification process. An immigrant mother who has not mourned adequately, with a different sociocultural background has to go through a far more complex development of motherhood. The case of an adolescent boy, Jason, demonstrates the impact of immigrant motherhood on his ego development. PMID- 27194273 TI - RACE AND RECOGNITION: THE TIME OF OUR SINGING. AB - Literature affords the opportunity to consider the racial fear, hatred and hostility that can flare in moments when the otherness in the human face occludes the common bonds that join us together. Richard Powers' (2003) compelling novel, The Time of Our Singing, highlights ways in which racial tensions continue to haunt us, impeding the efforts of successive generations to heal the wounds and move forward. In the novel, the parents' efforts to move "beyond race" leave their children utterly unprepared for the ways in which race informs and obstruct their experience, as what has been denied returns to haunt them. PMID- 27194274 TI - GEORG GRODDECK: "THE PINCH OF PEPPER" OF PSYCHOANALYSIS(.). AB - The life and works of Georg Groddeck are reviewed and placed in historical context as a physician and a pioneer of psychoanalysis, psychosomatic medicine, and an epistolary style of writing. His Das Es concept stimulated Freud to construct his tripartite model of the mind. Groddeck, however, used Das Es to facilitate receptivity to unconscious communication with his patients. His "maternal turn" transformed his treatment approach from an authoritarian position to a dialectical process. Groddeck was a generative influence on the development of Frieda Fromm-Reichmann, Erich Fromm, and Karen Horney. He was also the mid wife of the late-life burst of creativity of his friend and patient Sandor Ferenczi. Together, Groddeck and Ferenczi provided the impetus for a paradigm shift in psychoanalysis that emphasized the maternal transference, child-like creativity, and a dialogue of the unconscious that foreshadowed contemporary interest in intersubjectivity and field theory. They were progenitors of the relational turn and tradition in psychoanalysis. Growing interest in interpsychic communication and field theory is bringing about a convergence of theorizing among pluralistic psychoanalytic schools that date back to 1923 when Freud appropriated Groddeck's Das Es and radically altered its meaning and use. PMID- 27194275 TI - THE DEAD-LIVING-MOTHER: MARIE BONAPARTE'S INTERPRETATION OF EDGAR ALLAN POE'S SHORT STORIES. AB - Princess Marie Bonaparte is an important figure in the history of psychoanalysis, remembered for her crucial role in arranging Freud's escape to safety in London from Nazi Vienna, in 1938. This paper connects us to Bonaparte's work on Poe's short stories. Founded on concepts of Freudian theory and an exhaustive review of the biographical facts, Marie Bonaparte concluded that the works of Edgar Allan Poe drew their most powerful inspirational force from the psychological consequences of the early death of the poet's mother. In Bonaparte's approach, which was powerfully influenced by her recognition of the impact of the death of her own mother when she was born-an understanding she gained in her analysis with Freud-the thesis of the dead-living-mother achieved the status of a paradigmatic key to analyze and understand Poe's literary legacy. This paper explores the background and support of this hypothesis and reviews Bonaparte's interpretation of Poe's most notable short stories, in which extraordinary female figures feature in the narrative. PMID- 27194276 TI - Lawrence J. Friedman: The Lives of Erich Fromm: Love's Prophet. PMID- 27194277 TI - Lawrence J. Friedman: The Lives of Erich Fromm: Love's Prophet. PMID- 27194278 TI - Prophecy Coles: The Shadow of the Second Mother: Nurses and Nannies in Theories of Infant Development. PMID- 27194279 TI - Frank Summers: The Psychoanalytic Vision: The Experiencing Subject, Transcendence, and the Therapeutic Process. PMID- 27194280 TI - Margaret Boyle Spelman: Winnicott's Babies and Winnicott's Patients: Psychoanalysis as Transitional Space. PMID- 27194282 TI - Family Violence in Domestic Homicides: A Case Study of Women Who Killed Intimate Partners Post-Legislative Reform in Victoria, Australia. AB - This article examines the impact of legislative reforms enacted in 2005 in Victoria, Australia, on legal responses to women charged with murder for killing their intimate partner. The reforms provided for a broader understanding of the context of family violence to be considered in such cases, but we found little evidence of this in practice. This is partly attributable to persistent misconceptions among the legal profession about family violence and why women may believe it necessary to kill a partner. We recommend specialized training for legal professionals and increased use of family violence evidence to help ensure women's claims of self-defense receive appropriate responses from Victorian courts. PMID- 27194281 TI - A brain-region-based meta-analysis method utilizing the Apriori algorithm. AB - BACKGROUND: Brain network connectivity modeling is a crucial method for studying the brain's cognitive functions. Meta-analyses can unearth reliable results from individual studies. Meta-analytic connectivity modeling is a connectivity analysis method based on regions of interest (ROIs) which showed that meta analyses could be used to discover brain network connectivity. RESULTS: In this paper, we propose a new meta-analysis method that can be used to find network connectivity models based on the Apriori algorithm, which has the potential to derive brain network connectivity models from activation information in the literature, without requiring ROIs. This method first extracts activation information from experimental studies that use cognitive tasks of the same category, and then maps the activation information to corresponding brain areas by using the automatic anatomical label atlas, after which the activation rate of these brain areas is calculated. Finally, using these brain areas, a potential brain network connectivity model is calculated based on the Apriori algorithm. The present study used this method to conduct a mining analysis on the citations in a language review article by Price (Neuroimage 62(2):816-847, 2012). The results showed that the obtained network connectivity model was consistent with that reported by Price. CONCLUSIONS: The proposed method is helpful to find brain network connectivity by mining the co-activation relationships among brain regions. Furthermore, results of the co-activation relationship analysis can be used as a priori knowledge for the corresponding dynamic causal modeling analysis, possibly achieving a significant dimension-reducing effect, thus increasing the efficiency of the dynamic causal modeling analysis. PMID- 27194283 TI - Predator odours attract other predators, creating an olfactory web of information. AB - Many studies have reported the aversive reactions of prey towards a predator's odour signals (e.g. urine marks), a behaviour widely thought to reduce the risk of predation by the predator. However, because odour signals persist in the environment, they are vulnerable to exploitation and eavesdropping by predators, prey and conspecifics. As such, scent patches created by one species might attract other species interested in information about their enemies. We studied this phenomenon by examining red fox investigation of odours from conspecifics and competing species in order to understand what prey are responding to when avoiding the odours of a predator. Surprisingly, foxes showed limited interest in conspecific odours but were highly interested in the odours of their competitors (wild dogs and feral cats), suggesting that odours are likely to play an important role in mediating competitive interactions. Importantly, our results identify that simple, dyadic interpretations of prey responses to a predator odour (i.e. cat odour = risk of cat encounter = fear of cats) can no longer be assumed in ecological or psychology research. Instead, interactions mediated by olfactory cues are more complex than previously thought and are likely to form a complicated olfactory web of interactions. PMID- 27194284 TI - The shield effect: nuptial gifts protect males against pre-copulatory sexual cannibalism. AB - Several not mutually exclusive functions have been ascribed to nuptial gifts across different taxa. Although the idea that a nuptial prey gift may protect the male from pre-copulatory sexual cannibalism is attractive, it has previously been considered of no importance based on indirect evidence and rejected by experimental tests. We reinvestigated whether nuptial gifts may function as a shield against female attacks during mating encounters in the spider Pisaura mirabilis and whether female hunger influences the likelihood of cannibalistic attacks. The results showed that pre-copulatory sexual cannibalism was enhanced when males courted without a gift and this was independent of female hunger. We propose that the nuptial gift trait has evolved partly as a counteradaptation to female aggression in this spider species. PMID- 27194285 TI - Are invasive fire ants kept in check by native aerial insectivores? AB - Aerial predator-prey interactions may impact populations of many terrestrial species. Here, we use altitude loggers to study aerial foraging in a native insectivore, the purple martin (Progne subis), in the southern USA. Purple martins fed primarily on mating queens and males of the invasive red imported fire ant (Solenopsis invicta), and doubled their foraging efficiency by doing so. Across the USA, purple martins likely eat billions of fire ant queens each year, potentially impacting the spread of this species. Alternatively, predation on fire ants may help sustain populations of purple martins and other aerial insectivores. PMID- 27194286 TI - Parasitic infection: a buffer against ocean acidification? AB - Recently, there has been a concerted research effort by marine scientists to quantify the sensitivity of marine organisms to ocean acidification (OA). Empirical data generated by this research have been used to predict changes to marine ecosystem health, biodiversity and productivity that will be caused by continued acidification. These studies have also found that the effects of OA on marine organisms can be significantly modified by additional abiotic stressors (e.g. temperature or oxygen) and biotic interactions (e.g. competition or predation). To date, however, the effects of parasitic infection on the sensitivity of marine organisms to OA have been largely ignored. We show that parasitic infection significantly altered the response of a marine gastropod to simulated OA conditions by reducing the mortality of infected individuals relative to uninfected conspecifics. Without the inclusion of infection data, our analysis would not have detected the significant effect of pH on host mortality. These results strongly suggest that parasitic infection may be an important confounding factor in OA research and must be taken into consideration when assessing the response of marine species to OA. PMID- 27194287 TI - Food supplementation mitigates dispersal-dependent differences in nest defence in a passerine bird. AB - Dispersing and non-dispersing individuals often differ in phenotypic traits (e.g. physiology, behaviour), but to what extent these differences are fixed or driven by external conditions remains elusive. We experimentally tested whether differences in nest-defence behaviour between dispersing and non-dispersing individuals changed with local habitat quality in collared flycatchers, by providing additional food during the nestling rearing period. In control (non food-supplemented) nests, dispersers were less prone to defend their brood compared with non-dispersers, whereas in food-supplemented nests, dispersing and non-dispersing individuals showed equally strong nest defence. We discuss the importance of dispersal costs versus adaptive flexibility in reproductive investment in shaping these differences in nest-defence behaviour between dispersing and non-dispersing individuals. Irrespective of the underlying mechanisms, our study emphasizes the importance of accounting for environmental effects when comparing traits between dispersing and non-dispersing individuals, and in turn assessing the costs and benefits of dispersal. PMID- 27194288 TI - Effects of antibiotic resistance alleles on bacterial evolutionary responses to viral parasites. AB - Antibiotic resistance has wide-ranging effects on bacterial phenotypes and evolution. However, the influence of antibiotic resistance on bacterial responses to parasitic viruses remains unclear, despite the ubiquity of such viruses in nature and current interest in therapeutic applications. We experimentally investigated this by exposing various Escherichia coli genotypes, including eight antibiotic-resistant genotypes and a mutator, to different viruses (lytic bacteriophages). Across 960 populations, we measured changes in population density and sensitivity to viruses, and tested whether variation among bacterial genotypes was explained by their relative growth in the absence of parasites, or mutation rate towards phage resistance measured by fluctuation tests for each phage. We found that antibiotic resistance had relatively weak effects on adaptation to phages, although some antibiotic-resistance alleles impeded the evolution of resistance to phages via growth costs. By contrast, a mutator allele, often found in antibiotic-resistant lineages in pathogenic populations, had a relatively large positive effect on phage-resistance evolution and population density under parasitism. This suggests costs of antibiotic resistance may modify the outcome of phage therapy against pathogenic populations previously exposed to antibiotics, but the effects of any co-occurring mutator alleles are likely to be stronger. PMID- 27194289 TI - 'Fire hardening' spear wood does slightly harden it, but makes it much weaker and more brittle. AB - It is usually assumed that 'fire hardening' the tips of spears, as practised by hunter-gatherers and early Homo spp., makes them harder and better suited for hunting. This suggestion was tested by subjecting coppiced poles of hazel to a fire-hardening process and comparing their mechanical properties to those of naturally seasoned poles. A Shore D hardness test showed that fire treatment slightly increased the hardness of the wood, but flexural and impact tests showed that it reduced the strength and work of fracture by 30% and 36%, respectively. These results suggest that though potentially slightly sharper and more durable, fire-hardened tips would actually be more likely to break off when used, as may have been the case with the earliest known wooden tool, the Clacton spear. Fire might first have been used to help sharpen the tips of spears, and fire-hardening would have been a mostly negative side effect, not its primary purpose. PMID- 27194290 TI - Temporal pairwise-correlation analysis provides empirical support for attention hierarchies in mice. AB - In many social hierarchies, more subordinate individuals adjust their behaviour according to the presence or behaviour of more dominant individuals. In this study, it is shown that male mice form linear dominance hierarchies characterized by individuals attacking in bursts. Temporal pairwise-correlation analysis reveals that non-dominant individuals avoid behaving aggressively concurrently with an aggressively behaving alpha male. This anti-correlation is only found with alpha males and is greater for more despotic alpha males. It is concluded that less dominant individuals modulate their aggressive behaviour in response to their social context, resulting in an attentional group structure. PMID- 27194291 TI - Nocturnal foraging enhanced by enlarged secondary eyes in a net-casting spider. AB - Animals that possess extreme sensory structures are predicted to have a related extreme behavioural function. This study focuses on one such extreme sensory structure-the posterior median eyes of the net-casting spider Deinopis spinosa. Although past research has implicated the importance of vision in the nocturnal foraging habits of Deinopis, no direct link between vision in the enlarged eyes and nocturnal foraging has yet been made. To directly test the hypothesis that the enlarged posterior median eyes facilitate visually based nocturnal prey capture, we conducted repeated-measures, visual occlusion trials in both natural and laboratory settings. Our results indicate that D. spinosa relies heavily on visual cues detected by the posterior median eyes to capture cursorial prey items. We suggest that the enlarged posterior median eyes benefit D. spinosa not only through increased diet breadth, but also by allowing spiders to remain active solely at night, thus evading predation by diurnal animals. PMID- 27194292 TI - Who directs group movement? Leader effort versus follower preference in stickleback fish of different personality. AB - During collective movement, bolder individuals often emerge as leaders. Here, we investigate whether this reflects a greater propensity of bold individuals to initiate movement, or a preference for shy individuals to follow a bolder leader. We set up trios of stickleback fish comprising a focal individual who was either bold or shy, and one other individual of each personality. We then recorded the movements of all individuals in and out of cover in a foraging context to determine how assiduously the focal fish followed the movements of each other partner. We found that a shy focal fish preferred to follow a leader whose personality matched its own, but we did not detect such a difference in bold fish. Despite this preference, however, the greater propensity of bold individuals to initiate movements out of cover meant that they successfully led more joint trips. Thus, when offered a choice of leaders, sticklebacks prefer to follow individuals whose personality matches their own, but bolder individuals may, nevertheless, be able to impose their leadership, even among shy followers, simply through greater effort. PMID- 27194293 TI - SPINAL SPECIAL EDITION EDITORIAL. PMID- 27194294 TI - The Association between Central Adiposity and Autonomic Dysfunction in Obesity. AB - OBJECTIVE: To determine the relationship between central adiposity parameters and autonomic nervous system (ANS) dysfunction. SUBJECTS AND METHODS: The study included 114 obese individuals without any cardiovascular risk factors. Weight (in kg), height (in m), and waist circumference (WC; in cm) were measured and body mass index was calculated. Echocardiographic examination was performed to measure left ventricular mass and epicardial fat thickness (EFT). All the participants underwent an exercise test and electrophysiological evaluation using electromyography. Heart rate recovery (HRR) at 1-5 min, R-R interval variation at rest and during hyperventilation, and sympathetic skin response were measured. Pearson's correlation analysis was used. Multiple linear regression analysis was used to identify the factors associated with autonomic dysfunction. RESULTS: The HRR at 1-5 min was negatively correlated with WC and age (WC-HRR1: r = -0.32; WC HRR2: r = -0.31; WC-HRR3: r = -0.26; WC-HRR4: r = -0.23; WC-HRR5: r = -0.21; age HRR2: r = -0.32; age-HRR3: r = -0.28; age-HRR4: r = -0.41; age-HRR5: r = -0.42). Age was the only independent predictor of reduced HRR at 1-5 min. In addition, WC predicted a reduced HRR at 3 min. There were no significant associations between central obesity and electrophysiological parameters. EFT was not associated with ANS dysfunction. CONCLUSION: In this study, central adiposity and aging were associated with ANS dysfunction in obese individuals. The WC could be a marker of ANS dysfunction in obese individuals without any cardiovascular risk factors. The HRR assessment at a later decay phase could be more valuable for evaluating ANS function than during early recovery. PMID- 27194295 TI - Posterolateral rotatory instability of the elbow. AB - Posterolateral rotatory instability of the elbow is often caused by a complex injury to the lateral ulnar collateral ligament complex. This often leads to chronic mechanical symptoms of instability and pain. Surgical repair or reconstruction of the ligament is often required to stabilize the radiocapitellar joint. Multiple techniques have been described in the literature for repair or reconstruction of the lateral ligamentous complex with overall good clinical outcomes. PMID- 27194296 TI - AMPK Negatively Regulates Peripheral Myelination via Activation of c-Jun. AB - The process of Schwann cells (SCs) forming a sheath around axons is termed as myelination, which plays a pivotal role for proper physiological function in the peripheral nervous system (PNS). The molecular mechanisms regulating SC myelination in the PNS remain to be elucidated. Here, we show that AMP-activated protein kinase (AMPK) in sciatic nerves was gradually decreased during the PNS myelination process. Pharmacological interventions showed that activation of AMPK by AICAR attenuated myelin gene expression in SCs, whereas inhibition of AMPK by Compound C (ComC) or AMPKalpha1 knockdown stimulated myelin gene expression. Following experiments revealed that c-Jun, a negative modulator of PNS myelination, was activated by AMPK in SCs. The application of ComC in newborn rats markedly downregulated c-Jun expression in sciatic nerves. The lipid and protein synthesis in sciatic nerves was greatly potentiated by ComC. As a consequence, myelin gene expression in sciatic nerves, as well as myelin sheath thickness, were promoted in the ComC-treated rats. All together, our data identify that AMPK is an important negative regulator of Schwann cell myelination in the PNS, and this regulation role may rely on c-Jun activation. PMID- 27194297 TI - Transitional Progenitors during Vertebrate Retinogenesis. AB - The retina is a delicate neural tissue responsible for light signal capturing, modulating, and passing to mid-brain. The brain then translated the signals into three-dimensional vision. The mature retina is composed of more than 50 subtypes of cells, all of which are developed from a pool of early multipotent retinal progenitors, which pass through sequential statuses of oligopotent, bipotent, and unipotent progenitors, and finally become terminally differentiated retinal cells. A transitional progenitor model is proposed here to describe how intrinsic developmental programs, along with environmental cues, control the step-by-step differentiation during retinogenesis. The model could elegantly explain many current findings as well as predict roles of intrinsic factors during retinal development. PMID- 27194301 TI - Early nutritional support for extremely premature infants: what amino acid amount should be given? PMID- 27194298 TI - Propitious Therapeutic Modulators to Prevent Blood-Spinal Cord Barrier Disruption in Spinal Cord Injury. AB - The blood-spinal cord barrier (BSCB) is a specialized protective barrier that regulates the movement of molecules between blood vessels and the spinal cord parenchyma. Analogous to the blood-brain barrier (BBB), the BSCB plays a crucial role in maintaining the homeostasis and internal environmental stability of the central nervous system (CNS). After spinal cord injury (SCI), BSCB disruption leads to inflammatory cell invasion such as neutrophils and macrophages, contributing to permanent neurological disability. In this review, we focus on the major proteins mediating the BSCB disruption or BSCB repair after SCI. This review is composed of three parts. Section 1. SCI and the BSCB of the review describes critical events involved in the pathophysiology of SCI and their correlation with BSCB integrity/disruption. Section 2. Major proteins involved in BSCB disruption in SCI focuses on the actions of matrix metalloproteinases (MMPs), tumor necrosis factor alpha (TNF-alpha), heme oxygenase-1 (HO-1), angiopoietins (Angs), bradykinin, nitric oxide (NO), and endothelins (ETs) in BSCB disruption and repair. Section 3. Therapeutic approaches discusses the major therapeutic compounds utilized to date for the prevention of BSCB disruption in animal model of SCI through modulation of several proteins. PMID- 27194299 TI - Anesthetic Isoflurane Induces DNA Damage Through Oxidative Stress and p53 Pathway. AB - DNA damage is associated with aging and neurological disorders, including Alzheimer's disease. Isoflurane is a commonly used anesthetic. It remains largely unknown whether isoflurane induces DNA damage. Phosphorylation of the histone protein H2A variant X at Ser139 (gammaH2A.X) is a marker of DNA damage. We therefore set out to assess the effects of isoflurane on gammaH2A.X level in H4 human neuroglioma cells and in brain tissues of mice. Oxidative stress, caspase activated DNase (CAD), and the p53 signaling pathway are involved in DNA damage. Thus, we determined the interaction of isoflurane with reactive oxygen species (ROS), CAD, and p53 to illustrate the underlying mechanisms. The cells were treated with 2 % isoflurane for 3 or 6 h. The mice were anesthetized with 1.4 % isoflurane for 2 h. Western blot, immunostaining and live cell fluorescence staining were used in the experiments. We showed that isoflurane increased levels of gammaH2A.X, cleaved caspase-3, and nucleus translocation of CAD and decreased levels of inhibitor of CAD (ICAD) and p53. Isoflurane enhanced the nucleus level of gammaH2A.X. Moreover, caspase inhibitor Z-VAD and ROS generation inhibitor N acetyl-L-cysteine (NAC) attenuated the isoflurane-induced increase in gammaH2A.X level. However, NAC did not significantly alter the isoflurane-induced reduction in p53 level. Finally, p53 activator (actinomycin D) and inhibitor (pifithrin alpha) attenuated and potentiated the isoflurane-induced increase in gammaH2A.X level, respectively. These findings suggest that isoflurane might induce DNA damage, as represented by increased gammaH2A.X level, via induction of oxidative stress and inhibition of the repair of DNA damage through the p53 signaling pathway. PMID- 27194302 TI - Can long-chain PUFA supplementation during pregnancy influence later obesity risk? PMID- 27194300 TI - Loss of Transient Receptor Potential Ankyrin 1 Channel Deregulates Emotion, Learning and Memory, Cognition, and Social Behavior in Mice. AB - The transient receptor potential ankyrin 1 (TRPA1) channel is a non-selective cation channel that helps regulate inflammatory pain sensation and nociception and the development of inflammatory diseases. However, the potential role of the TRPA1 channel and the underlying mechanism in brain functions are not fully resolved. In this study, we demonstrated that genetic deletion of the TRPA1 channel in mice or pharmacological inhibition of its activity increased neurite outgrowth. In vivo study in mice provided evidence of the TRPA1 channel as a negative regulator in hippocampal functions; functional ablation of the TRPA1 channel in mice enhanced hippocampal functions, as evidenced by less anxiety-like behavior, and enhanced fear-related or spatial learning and memory, and novel location recognition as well as social interactions. However, the TRPA1 channel appears to be a prerequisite for motor function; functional loss of the TRPA1 channel in mice led to axonal bundle fragmentation, downregulation of myelin basic protein, and decreased mature oligodendrocyte population in the brain, for impaired motor function. The TRPA1 channel may play a crucial role in neuronal development and oligodendrocyte maturation and be a potential regulator in emotion, cognition, learning and memory, and social behavior. PMID- 27194303 TI - Vitamin C supplement intake and postmenopausal breast cancer risk: interaction with dietary vitamin C. AB - BACKGROUND: Experimental and epidemiologic studies have yielded conflicting results on the relation between vitamin C intake and breast cancer risk. OBJECTIVE: We investigated the relation between vitamin C supplement intake and breast cancer risk while considering dietary vitamin C intake. DESIGN: Between 1995 and 2008, 2482 invasive breast cancer cases occurred in 57,403 postmenopausal women from the Etude Epidemiologique aupres de femmes de la Mutuelle Generale de l'Education Nationale (E3N) prospective cohort during 581,085 person-years. We estimated vitamin C intake from foods with the use of a validated food-frequency questionnaire that was sent to subjects in 1993-1995 and vitamin C supplement use via questionnaires sent in 1995, 2000, 2002, and 2005. Multivariable HRs (95% CIs) for primary invasive breast cancer were estimated with the use of Cox regression models. All statistical tests were 2-sided. RESULTS: Vitamin C supplement use (ever compared with never) was not associated with breast cancer risk overall; it was associated with higher breast cancer risk in women in the fourth quartile of vitamin C intake from foods (HR: 1.32; 95% CI: 1.04, 1.67) but not in other quartiles of dietary vitamin C intake (P-interaction = 0.03). CONCLUSIONS: We observed that vitamin C supplement use was associated with increased postmenopausal breast cancer risk in women with high vitamin C intake from foods. Our data suggest a potential U- or J-shaped relation between total vitamin C intake and postmenopausal breast cancer risk that deserves further investigation. PMID- 27194304 TI - Combined epigallocatechin-3-gallate and resveratrol supplementation for 12 wk increases mitochondrial capacity and fat oxidation, but not insulin sensitivity, in obese humans: a randomized controlled trial. AB - BACKGROUND: The obese insulin-resistant state is characterized by impairments in lipid metabolism. We previously showed that 3-d supplementation of combined epigallocatechin-3-gallate and resveratrol (EGCG+RES) increased energy expenditure and improved the capacity to switch from fat toward carbohydrate oxidation with a high-fat mixed meal (HFMM) test in men. OBJECTIVE: The present study aimed to investigate the longer-term effect of EGCG+RES supplementation on metabolic profile, mitochondrial capacity, fat oxidation, lipolysis, and tissue specific insulin sensitivity. DESIGN: In this randomized double-blind study, 38 overweight and obese subjects [18 men; aged 38 +/- 2 y; body mass index (kg/m(2)): 29.7 +/- 0.5] received either EGCG+RES (282 and 80 mg/d, respectively) or placebo for 12 wk. Before and after the intervention, oxidative capacity and gene expression were assessed in skeletal muscle. Fasting and postprandial (HFMM) lipid metabolism was assessed by using indirect calorimetry, blood sampling, and microdialysis. Tissue-specific insulin sensitivity was assessed by a hyperinsulinemic-euglycemic clamp with [6,6-(2)H2]-glucose infusion. RESULTS: EGCG+RES supplementation did not affect the fasting plasma metabolic profile. Although whole-body fat mass was not affected, visceral adipose tissue mass tended to decrease after the intervention compared with placebo (P-time * treatment = 0.09). EGCG+RES supplementation significantly increased oxidative capacity in permeabilized muscle fibers (P-time * treatment < 0.05, P-EGCG+RES < 0.05). Moreover, EGCG+RES reduced fasting (P-time * treatment = 0.03) and postprandial respiratory quotient (P-time * treatment = 0.01) compared with placebo. Fasting and postprandial fat oxidation was not significantly affected by EGCG+RES (P-EGCG+RES = 0.46 and 0.38, respectively) but declined after placebo (P placebo = 0.05 and 0.03, respectively). Energy expenditure was not altered (P time * treatment = 0.96). Furthermore, EGCG+RES supplementation attenuated the increase in plasma triacylglycerol concentrations during the HFMM test that was observed after placebo (P-time * treatment = 0.04, P-placebo = 0.01). Finally, EGCG+RES had no effect on insulin-stimulated glucose disposal, suppression of endogenous glucose production, or lipolysis. CONCLUSION: Twelve weeks of EGCG+RES supplementation increased mitochondrial capacity and stimulated fat oxidation compared with placebo, but this did not translate into increased tissue-specific insulin sensitivity in overweight and obese subjects. This trial was registered at clinicaltrials.gov as NCT02381145. PMID- 27194305 TI - Consumption of fruit and vegetables and risk of frailty: a dose-response analysis of 3 prospective cohorts of community-dwelling older adults. AB - BACKGROUND: Consuming fruit and vegetables (FVs) may protect against frailty, but to our knowledge no study has yet assessed their prospective dose-response relation. OBJECTIVE: We sought to examine the dose-response association between FV consumption and the risk of frailty in older adults. DESIGN: Data were taken from 3 independent cohorts of community-dwelling older adults: the Seniors-ENRICA (Study on Nutrition and Cardiovascular Risk Factors in Spain) cohort (n = 1872), Three-City (3C) Bordeaux cohort (n = 581), and integrated multidisciplinary approach cohort (n = 473). Baseline food consumption was assessed with a validated computerized diet history (Seniors-ENRICA) or with a food-frequency questionnaire (3C Bordeaux and AMI). In all cohorts, incident frailty was assessed with the use of the Fried criteria. Results across cohorts were pooled with the use of a random-effects model. RESULTS: During a mean 2.5-y follow-up, 300 incident frailty cases occurred. Fully adjusted models showed that the pooled ORs (95% CIs) of incident frailty comparing participants who consumed 1, 2, or >=3 portions of fruit/d to those with no consumption were, respectively, 0.59 (0.27, 0.90), 0.58 (0.29, 0.86), and 0.48 (0.20, 0.75), with a P-trend of 0.04. The corresponding values for vegetables were 0.69 (0.42, 0.97), 0.56 (0.35, 0.77), and 0.52 (0.13, 0.92), with a P-trend < 0.01. When FVs were analyzed together, the pooled ORs (95% CIs) of incident frailty were 0.41 (0.21, 0.60), 0.47 (0.25, 0.68), 0.36 (0.18, 0.53), and 0.31 (0.13, 0.48), with a P-trend < 0.01 for participants who consumed 2, 3, 4, or >=5 portions/d, respectively, compared with those who consumed <=1 portion/d. An inverse dose-response relation was also found between the baseline consumption of fruit and risk of exhaustion, low physical activity, and slow walking speed, whereas the consumption of vegetables was associated with a decreased risk of exhaustion and unintentional weight loss. CONCLUSIONS: Among community-dwelling older adults, FV consumption was associated with a lower short-term risk of frailty in a dose-response manner, and the strongest association was obtained with 3 portions of fruit/d and 2 portions of vegetables/d. PMID- 27194306 TI - Association between barriers and facilitators to meeting the Dietary Guidelines for Americans and body weight status of caregiver-child dyads: the Healthy Eating and Lifestyle for Total Health Study. AB - BACKGROUND: Few Americans meet the Dietary Guidelines for Americans (DGA), yet a large percentage are overweight. OBJECTIVE: The goal of this research was to examine the association between barriers and facilitators to meeting the DGA and weight in a multisite study. DESIGN: This was a cross-sectional study in which 836 caregiver-child dyads among 3 race/ethnic groups completed the questionnaire across 6 sites participating in the HEALTH (Healthy Eating and Lifestyle for Total Health) Study. Barriers and facilitators to meeting the DGA were assessed by using a validated questionnaire developed specifically for the HEALTH Study. Heights and weights were measured. A series of bivariate regression analyses were conducted to examine the association between caregiver body mass index (BMI) or child BMI z score and the barriers and facilitators to meeting the DGA, adjusting for appropriate covariates in the models. Path analysis was used to examine the relation of caregiver and child barriers and facilitators to their relative BMIs. RESULTS: In children, the BMI z score was associated positively (P < 0.001) with total barriers and negatively (P < 0.001) with total facilitators. In caregivers, BMI was associated positively only with total barriers (P < 0.0001). For each of the 8 MyPyramid components, barriers consistently were associated positively (P < 0.0001) and facilitators were associated negatively (P < 0.001) with BMI z score in children (with the exception of the fruit and physical activity components). For caregivers, most of the barriers to meeting recommendations for meats and beans; solid fats, alcohol, and added sugars; and physical activity components were associated positively (P < 0.01) with BMI. Path analyses show that caregiver facilitators were significantly related to children's facilitators to meeting DGA recommendations (standardized beta: 0.12; P < 0.001). CONCLUSION: To our knowledge, our findings are among the first to show associations between weight and barriers and/or facilitators to meeting the DGA in a national, large sample of caregiver-child dyads. This trial was registered at clinicaltrials.gov as NCT02725970. PMID- 27194307 TI - Insulin sensitivity is a Rubik's Cube. PMID- 27194308 TI - Vitamin D status of black and white Americans and changes in vitamin D metabolites after varied doses of vitamin D supplementation. AB - BACKGROUND: Controversy exists over the disparate circulating 25-hydroxyvitamin D [25(OH)D] concentrations between black and white Americans. OBJECTIVE: We sought to determine whether there are differences in total and directly measured free 25(OH)D concentrations between black and white American adults and how daily supplementation with cholecalciferol changes these concentrations. DESIGN: Cross sectional and longitudinal analyses were conducted with the use of data from 2 placebo-controlled, randomized trials at 2 academic medical centers in the United States: CaDDM (Calcium and Vitamin D in Type 2 Diabetes) and DDM2 (Vitamin D for Established Type 2 Diabetes). A total of 208 subjects with pre- or well controlled diabetes with a mean age of 59.1 y and mean body mass index (BMI; in kg/m(2)) of 31.6 were randomly assigned to receive daily cholecalciferol supplementation at 1 of 2 doses (2000 or 4000 IU) or a matching placebo for 16 wk. We measured serum total 25(OH)D, vitamin D-binding protein (DBP) by 2 different immunoassays (with the use of monoclonal or polyclonal antibodies), parathyroid hormone, and albumin. Free 25(OH)D concentration was directly measured and calculated. RESULTS: Blacks had lower total 25(OH)D concentrations than whites [adjusted median: 20.3 ng/mL (95% CI: 16.2, 24.5 ng/mL) compared with 26.7 ng/mL (95% CI: 25.2, 28.1 ng/mL), respectively; P = 0.026)], and a higher proportion of blacks had total 25(OH)D concentrations <20 ng/mL (46% compared with 19%, respectively; P < 0.001). Directly measured free 25(OH)D concentrations were lower in blacks than in whites [adjusted median: 4.5 ng/mL (95% CI: 3.7, 5.4 ng/mL) compared with 5.7 ng/mL (95% CI: 5.4, 5.9 ng/mL), respectively; P = 0.044] and were strongly correlated with total 25(OH)D without an effect of race. DBP was lower in blacks when measured by the monoclonal but not the polyclonal antibody immunoassay. Cholecalciferol supplementation increased total and measured free 25(OH)D concentrations proportionally to the dose and without a difference between races. CONCLUSIONS: The relation between free and total 25(OH)D did not vary systematically by race in this multiracial population with pre- or well-controlled diabetes. The results need to be replicated in additional cohorts before concluding that the clinical assessment of vitamin D status in blacks and whites should follow a single standard. The CaDDM and DDM2 trials were registered at clinicaltrials.gov as NCT00436475 and NCT01736865, respectively. PMID- 27194309 TI - Greater diet quality is associated with more optimal glycemic control in a longitudinal study of youth with type 1 diabetes. AB - BACKGROUND: Despite the centrality of nutrition in the management of type 1 diabetes, the association of diet quality and macronutrient distribution with glycemic control is ambiguous. OBJECTIVE: This study examined longitudinally the association of dietary intake with multiple indicators of glycemic control in youth with type 1 diabetes participating in a behavioral nutrition intervention study. DESIGN: Participants in a randomized clinical trial of a behavioral nutrition intervention [n = 136; mean +/- SD age: 12.8 +/- 2.6 y; glycated hemoglobin (HbA1c): 8.1% +/- 1.0%; 69.1% using an insulin pump] completed 3-d diet records at baseline and months 3, 6, 9, 12, and 18; masked continuous glucose monitoring (CGM) data were obtained concurrently with the use of the Medtronic iPro CGM system. HbA1c was obtained every 3 mo; 1,5-anhydroglucitol was obtained every 6 mo. Linear mixed-effects regression models estimated associations of time-varying dietary intake variables with time-varying glycemic control indicators, controlling for age, height, weight, sex, Tanner stage, diabetes duration, regimen, frequency of blood glucose monitoring, physical activity, and treatment assignment. RESULTS: HbA1c was associated inversely with carbohydrate and natural sugar, and positively with protein and unsaturated fat. 1,5-Anhydroglucitol was associated positively with fiber intake and natural sugar. Greater glycemic control as indicated by >=1 CGM variable was associated with higher Healthy Eating Index-2005, whole plant food density, fiber, carbohydrate, and natural sugar and lower glycemic index and unsaturated fat. CONCLUSIONS: Both overall diet quality and macronutrient distribution were associated with more optimal glycemic control. Associations were more consistent for CGM variables obtained concurrently with dietary intake than for biomarkers of longer-term glycemic control. These findings suggest that glycemic control may be improved by increasing intake of high-fiber, low glycemic-index, carbohydrate containing foods. This trial was registered at clinicaltrials.gov as NCT00999375. PMID- 27194312 TI - Why Cancer? PMID- 27194311 TI - Distribution of coat-color-associated alleles in the domestic horse population and Przewalski's horse. AB - Considering the hidden mode of inheritance of some coat-color-associated alleles, we investigated the presence/absence of coat-color-associated alleles in 1093 domestic horses of 55 breeds and 20 specimens of Przewalski's horse. For coat color genotyping, allele specific PCR, pyrosequencing and Li-Cor analyses were conducted on 12 coat-color-associated alleles of five genes. Our data provide deep insight into the distribution of coat-color-associated alleles within breeds. We found that the alleles for the basic colorations (bay, black, and chestnut) are widely distributed and occur in nearly all breeds. Alleles leading to dilutions or patterns are rare in domestic breeds and were not found in Przewalski's horse. Higher frequencies of these alleles are only found in breeds that are selected for their expressed phenotypes (e.g., Kinsky horse, Lewitzer, Tinker). Nevertheless, our study produced strong evidence that molecular testing of the coat color is necessary for well-defined phenotyping to avoid unexpected colorations of offspring that can result in legal action. PMID- 27194313 TI - Correction. PMID- 27194314 TI - Association between treatment for gonorrhoea and chlamydia and lower condom use in a cross-sectional study of female sex workers in southern India. AB - OBJECTIVES: To assess whether having received grey packets containing treatment for gonorrhoea and chlamydia was associated with condom use among female sex workers (FSWs) in 5 districts of southern India covered by the Avahan programme where both periodic presumptive treatment (PPT) and syndromic management were used to control these sexually transmitted infections (STIs) among FSWs. SETTING: Cross-sectional study of FSWs recruited in the field in 5 districts of southern India (Bangalore, Belgaum, Bellary, Guntur and Mumbai) in 2006-2007. PARTICIPANTS: 1378 self-identified FSWs out of 1442 were approached to participate in the study (participation rate: 95.6%). The only exclusion criterion was to be aged <18 years. PRIMARY AND SECONDARY OUTCOME MEASURES: Consistent condom use (CCU) with new or occasional clients, and with the most recent repeat client as assessed using a questionnaire administered through face to-face interviews. RESULTS: Using the Poisson regression to model the association between the number of grey packets received in the past 3-12 months and reported CCU, adjusting for factors associated with condom use and other potential confounders in our data, CCU was lowest among FSWs who had received >=3 grey packets in the past 3-12 months with their new or occasional clients (adjusted prevalence ratio (APR): 0.70, 95% CI 0.57 to 0.84, p<0.001) and with the most recent repeat client (APR 0.63, 95% CI 0.51 to 0.78, p<0.001). Tests for trends showed that CCU with both types of clients decreased with the number of grey packets received (p<0.001). CONCLUSIONS: Since we could not distinguish grey packets used for PPT from those given for syndromic management, these results could be either due to a perception of protection conferred by PPT or by the fact that inconsistent condom users are more at risk for STIs. Further research on the potential disinhibiting effect of PPT is warranted. PMID- 27194316 TI - Qualitative study investigating the commissioning process for older people's services provided by third sector organisations: SOPRANO study protocol. AB - INTRODUCTION: The commissioning of third sector services for older people may influence the quality, availability and coordination of services for older people. The SOPRANO study aims to understand the relationships between and processes of commissioning bodies and third sector organisations providing health and social care services for older people. METHODS AND ANALYSIS: This qualitative study will be based in the East Midlands region of England. An initial scoping survey of commissioners will give an overview of services to maintain the health and well-being of older people in the community that are commissioned. Following this, semistructured interviews will be conducted with 4 sample groups: health and social care commissioners, service provider managers, service provider case workers and older service users. A sample size of 10-15 participants in each of the 4 groups is expected to be sufficient to reach data saturation, resulting in a final expected sample size of 40-60 participants. Informed consent will be gained from all participants, and those unable to provide informed consent will be excluded. The interview data will be analysed by 2 researchers using framework content analysis. ETHICS AND DISSEMINATION: Approval for the study has been gained from the University of Nottingham School of Medicine ethical review board, and the relevant approvals have been gained from the National Health Service (NHS) research and development departments for interviewing NHS staff. Early engagement with a wide range of stakeholders will ensure that the research findings are extensively disseminated to relevant stakeholders (including commissioners and third sector providers) in an accessible format using the extensive communication networks available to the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care CLAHRCs (applied health research organisations covering all of England). The study will also be disseminated through academic routes such as conference presentations and journal papers. PMID- 27194315 TI - Health effects of training laypeople to deliver emergency care in underserviced populations: a systematic review protocol. AB - INTRODUCTION: The Disease Control Priorities Project recommends emergency care training for laypersons in low-resource settings, but evidence for these interventions has not yet been systematically reviewed. This review will identify the individual and community health effects of educating laypeople to deliver prehospital emergency care interventions in low-resource settings. METHODS AND ANALYSIS: This systematic review addresses the following question: in underserviced populations and low-resource settings (P), does first aid or emergency care training or education for laypeople (I) confer any individual or community health benefit for emergency health conditions (O), in comparison with no training or other forms of education (C)? We restrict this review to studies reporting quantitatively measurable outcomes, and search 12 electronic bibliographic databases and grey literature sources. A team of expert content and methodology reviewers will conduct title and abstract screening and full-text review, using a custom-built online platform. Two investigators will independently extract methodological variables and outcomes related to patient level morbidity and mortality and community-level effects on resilience or emergency care capacity. Two investigators will independently assess external validity, selection bias, performance bias, measurement bias, attrition bias and confounding. We will summarise the findings using a narrative approach to highlight similarities and differences between the gathered studies. ETHICS AND DISSEMINATION: Formal ethical approval is not required. RESULTS: The results will be disseminated through a peer-reviewed publication and knowledge translation strategy. REVIEW REGISTRATION NUMBER: CRD42014009685. PMID- 27194317 TI - Protocol for Care After Lymphoma (CALy) trial: a phase II pilot randomised controlled trial of a lymphoma nurse-led model of survivorship care. AB - INTRODUCTION: Lymphoma is the sixth most common cancer diagnosed in Australia and internationally. Owing to the aggressive nature of the disease and intensity of treatment, survivors face long-term effects that impact on quality of life. Current models of follow-up post-treatment fail to address these complex issues. Given that 74% of patients with lymphoma cancer now survive 5 years beyond diagnosis and treatment, it is important to address this gap in care. AIM: To determine self-reported informational and practical needs, anxiety, depression, stress, coping and empowerment at baseline, 3 and 6 months. METHODS AND ANALYSIS: A pilot randomised controlled trial will test the effect of a nurse-led lymphoma survivorship clinic compared with usual post-treatment care at a large tertiary cancer centre in Western Australia. The intervention will comprise three face-to face appointments with delivery of tailored resources, a survivorship care plan and treatment summary (SCP TS). The SCP TS will be given to the participant and general practitioner (GP). Intervention participants will be interviewed at completion to explore the perceived value of the intervention components and preferred dose. An evaluation developed for GPs will assess receipt and use of SCP TS. The primary intent of analysis will be to address the feasibility of a larger trial and requisite effect and sample size. ETHICS AND DISSEMINATION: Ethics approval has been granted by the University of Notre Dame Australia and Sir Charles Gairdner Hospital in Western Australia. Peer-reviewed publications and conference presentations will report the results of this phase II trial. TRIAL REGISTRATION NUMBER: ANZCTRN12615000530527; Pre-results. PMID- 27194318 TI - Intrathecal hyperbaric versus isobaric bupivacaine for adult non-caesarean section surgery: systematic review protocol. AB - INTRODUCTION: Bupivacaine is the most commonly used local anaesthetic for spinal anaesthesia (SA). There are two forms of commercially available bupivacaine; isobaric bupivacaine (IB): a formulation with a specific gravity or density equal to cerebrospinal fluid, and hyperbaric bupivacaine (HB): a formulation with density heavier than cerebrospinal fluid. The difference in densities of the two available preparations is believed to affect the diffusion pattern that determines the effectiveness, spread and side-effect profile of bupivacaine. This systematic review will summarise the best available evidence regarding the effectiveness and safety on the use of HB compared with IB, when used to provide SA for surgery. Primarily, we will analyse the need for conversion to general anaesthesia. As secondary outcomes, we will compare the incidence of hypotension, incidence of nausea/vomiting, the onset time and duration of anaesthesia. METHODS AND ANALYSIS: We will search key electronic databases using search strategy (1) injections, spinal OR intrathecal OR subarachnoid; (2) bupivacaine OR levobupivacaine; (3) hypobaric OR isobaric OR plain; (4) baricity. We will search MEDLINE, EMBASE and Cochrane databases, from their inception for randomised controlled trials, with no restrictions on language. Caesarean section surgery will be excluded. 2 reviewers will independently extract the data using a standardised form. Extracted items will include study characteristics, risk of bias domains, as per modified Cochrane risk of bias, participant disposition and study outcomes. We will conduct a meta-analysis for variables that can be compared across the studies. We will evaluate clinical heterogeneity by qualitatively appraising differences in study characteristics in participants, interventions and the outcomes assessed. We will report our findings as relative risks (dichotomous), and weighted mean differences (continuous) for individual outcomes, along with their 95% CIs. ETHICS AND DISSEMINATION: We plan to submit, and will publish, our findings in a peer-reviewed scientific journal, and present our results at national and international meetings. TRIAL REGISTRATION NUMBER: CRD42015017672. PMID- 27194319 TI - System-level and patient-level explanations for non-attendance at diabetic retinopathy screening in Sutton and Merton (London, UK): a qualitative analysis of a service evaluation. AB - OBJECTIVES: Non-attendance at diabetic retinopathy screening has financial implications for screening programmes and potential clinical costs to patients. We sought to identify explanations for why patients had never attended a screening appointment (never attendance) in one programme. DESIGN: Qualitative analysis of a service evaluation. SETTING: One South London (UK) diabetic eye screening programme. PARTICIPANTS AND PROCEDURE: Patients who had been registered with one screening programme for at least 18 months and who had never attended screening within the programme were contacted by telephone to ascertain why this was the case. Patients' general practices were also contacted for information about why each patient may not have attended. Framework analysis was used to interpret responses. RESULTS: Of the 296 patients, 38 were not eligible for screening and of the 258 eligible patients, 159 were not contactable (31 of these had phone numbers that were not in use). We obtained reasons from patients/general practices/clinical notes for non-attendance for 146 (57%) patients. A number of patient-level and system-level factors were given to explain non-attendance. Patient-level factors included having other commitments, being anxious about screening, not engaging with any diabetes care and being misinformed about screening. System-level factors included miscommunication about where the patient lives, their clinical situation and practical problems that could have been overcome had their existence been shared between programmes. CONCLUSIONS: This service evaluation provides unique insight into the patient level and system-level reasons for never attendance at diabetic retinopathy screening. Improved sharing of relevant information between providers has the potential to facilitate increased uptake of screening. Greater awareness of patient-level barriers may help providers offer a more accessible service. PMID- 27194323 TI - Capitalizing on Directed Evolution and Rational Protein Engineering to Expand the Neuroscientist's Imaging Toolbox. PMID- 27194324 TI - Bilingual Language Control Mechanisms in Anterior Cingulate Cortex and Dorsolateral Prefrontal Cortex: A Developmental Perspective. PMID- 27194322 TI - Why take the chance? A qualitative grounded theory study of nocturnal haemodialysis recipients who decline kidney transplantation. AB - OBJECTIVE: The objective of this study was to examine the factors that influence decision-making to forgo transplantation in favour of remaining on nocturnal haemodialysis (NHD). DESIGN: A grounded theory approach using in-depth telephone interviewing was used. SETTING: Participants were identified from 2 tertiary care renal programmes in Canada. PARTICIPANTS: The study participants were otherwise eligible patients with end-stage renal disease who have opted to remain off of the transplant list. A total of 7 eligible participants were interviewed. 5 were male. The mean age was 46 years. ANALYSIS: A constant comparative method of analysis was used to identify a core category and factors influencing the decision-making process. RESULTS: In this grounded theory study of people receiving NHD who refused kidney transplantation, the core category of 'why take a chance when things are going well?' was identified, along with 4 factors that influenced the decision including 'negative past experience', 'feeling well on NHD', 'gaining autonomy' and 'responsibility'. CONCLUSIONS: This study provides insight into patients' thought processes surrounding an important treatment decision. Such insights might help the renal team to better understand, and thereby respect, patient choice in a patient-centred care paradigm. Findings may also be useful in the development of education programmes addressing the specific concerns of this population of patients. PMID- 27194321 TI - Antidepressants and the risk of hyponatremia: a Danish register-based population study. AB - OBJECTIVE: To examine the association between classes of antidepressants and hyponatremia, and between specific antidepressants and hyponatremia. DESIGN: Retrospective register-based cohort study using nationwide registers from 1998 to 2012. SETTING: The North Denmark Region. PARTICIPANTS: In total, 638 352 individuals were included. PRIMARY AND SECONDARY OUTCOME MEASURES: Plasma sodium was obtained from the LABKA database. The primary outcome was hyponatremia defined as plasma sodium (p-sodium) below 135 mmol/L and secondary outcome was severe hyponatremia defined as p-sodium below 130 mmol/L. The association between use of specific antidepressants and hyponatremia was analysed using multivariable Poisson regression models. RESULTS: An event of hyponatremia occurred in 72 509 individuals and 11.36% (n=6476) of these events happened during treatment with antidepressants. Incidence rate ratios and CIs for the association with hyponatremia in the first p-sodium measured after initiation of treatment were for citalopram 7.8 (CI 7.42 to 8.20); clomipramine 4.93 (CI 2.72 to 8.94); duloxetine 2.05 (CI 1.44 to 292); venlafaxine 2.90 (CI 2.43 to 3.46); mirtazapine 2.95 (CI 2.71 to 3.21); and mianserin 0.90 (CI 0.71 to 1.14). CONCLUSIONS: All antidepressants except mianserin are associated with hyponatremia. The association is strongest with citalopram and lowest with duloxetine, venlafaxine and mirtazapine. PMID- 27194325 TI - Pin1 Modulates the Synaptic Content of NMDA Receptors via Prolyl-Isomerization of PSD-95. AB - Phosphorylation of serine/threonine residues preceding a proline regulates the fate of its targets through postphosphorylation conformational changes catalyzed by the peptidyl-prolyl cis-/trans isomerase Pin1. By flipping the substrate between two different functional conformations, this enzyme exerts a fine-tuning of phosphorylation signals. Pin1 has been detected in dendritic spines and shafts where it regulates protein synthesis required to sustain the late phase of long term potentiation (LTP). Here, we demonstrate that Pin1 residing in postsynaptic structures can interact with postsynaptic density protein-95 (PSD-95), a key scaffold protein that anchors NMDA receptors (NMDARs) in PSD via GluN2-type receptor subunits. Pin1 recruitment by PSD-95 occurs at specific serine threonine/proline consensus motifs localized in the linker region connecting PDZ2 to PDZ3 domains. Upon binding, Pin1 triggers structural changes in PSD-95, thus negatively affecting its ability to interact with NMDARs. In electrophysiological experiments, larger NMDA-mediated synaptic currents, evoked in CA1 principal cells by Schaffer collateral stimulation, were detected in hippocampal slices obtained from Pin1(-/-) mice compared with controls. Similar results were obtained in cultured hippocampal cells expressing a PSD-95 mutant unable to undergo prolyl-isomerization, thus indicating that the action of Pin1 on PSD-95 is critical for this effect. In addition, an enhancement in spine density and size was detected in CA1 principal cells of Pin1(-/-) or in Thy-1GFP mice treated with the pharmacological inhibitor of Pin1 catalytic activity PiB.Our data indicate that Pin1 controls synaptic content of NMDARs via PSD-95 prolyl isomerization and the expression of dendritic spines, both required for LTP maintenance. SIGNIFICANCE STATEMENT: PSD-95, a membrane-associated guanylate kinase, is the major scaffolding protein at excitatory postsynaptic densities and a potent regulator of synaptic strength and plasticity. The activity of PSD-95 is tightly controlled by several post-translational mechanisms including proline directed phosphorylation. This signaling cascade regulates the fate of its targets through postphosphorylation conformational modifications catalyzed by the peptidyl-prolyl cis-/trans isomerase Pin1. Here, we uncover a new role of Pin1 in glutamatergic signaling. By interacting with PSD-95, Pin1 dampens PSD-95 ability to complex with NMDARs, thus negatively affecting NMDAR signaling and spine morphology. Our findings further emphasize the emerging role of Pin1 as a key modulator of synaptic transmission. PMID- 27194326 TI - Bcl-xL Is Essential for the Survival and Function of Differentiated Neurons in the Cortex That Control Complex Behaviors. AB - Apoptosis plays an essential role during brain development, yet the precise mechanism by which this pathway is regulated in the brain remains unknown. In particular, mammalian cells are known to express multiple anti-apoptotic Bcl-2 family proteins. However, the cells of the developing brain could also exist in a primed state in which the loss of a single anti-apoptotic Bcl-2 family protein is sufficient to trigger apoptosis. Here, we examined the critical role of Bcl-xL, an anti-apoptotic protein, during brain development. Using conditional knock-out mice in which Bcl-xL is deleted in neural progenitor cells (Bcl-xL(Emx1-Cre)), we show that the loss of Bcl-xL is not sufficient to trigger apoptosis in these proliferating progenitors. In contrast, specific populations of postmitotic neurons derived from these progenitors, including upper layer cortical neurons and the CA1-CA3 regions of the hippocampus, were acutely dependent on Bcl-xL. Consistent with this finding, deletion of Bcl-xL selectively in the postmitotic neurons in the brain (Bcl-xL(Nex-Cre)) also resulted in similar patterns of apoptosis. This Bcl-xL deficiency-induced neuronal death was a consequence of activation of the apoptotic pathway, because the cell death was rescued with codeletion of the proapoptotic proteins Bax and Bak. Importantly, the loss of these Bcl-xL-dependent neurons led to severe neurobehavioral abnormalities, including deficits in motor learning, hyperactivity, and increased risk-taking and self-injurious behaviors. Together, our results identify a population of neurons in the developing brain that are acutely dependent on Bcl-xL during the peak period of synaptic connectivity that are important for the establishment of higher-order complex behaviors. SIGNIFICANCE STATEMENT: Although Bcl-xL is known to inhibit apoptosis, exactly which cells in the brain are dependent on Bcl-xL has remained unclear because of the embryonic lethality of mice globally deleted for Bcl-xL. Here, we conditionally deleted Bcl-xL in the brain and found that this did not result in widespread apoptosis in the proliferating progenitors. Instead, Bcl-xL deficiency induced apoptosis in a select population of differentiated neurons predominantly in the early postnatal stages. Importantly, these Bcl-xL-dependent neurons are not essential for survival of the organism but instead regulate complex behaviors. Our results show that the selective loss of these Bcl-xL-dependent neurons results in mice exhibiting severe neurobehavioral abnormalities, including self-injurious and risk-taking behaviors, hyperactivity, and learning and memory defects. PMID- 27194327 TI - Multimodal Feature Integration in the Angular Gyrus during Episodic and Semantic Retrieval. AB - Much evidence from distinct lines of investigation indicates the involvement of angular gyrus (AnG) in the retrieval of both episodic and semantic information, but the region's precise function and whether that function differs across episodic and semantic retrieval have yet to be determined. We used univariate and multivariate fMRI analysis methods to examine the role of AnG in multimodal feature integration during episodic and semantic retrieval. Human participants completed episodic and semantic memory tasks involving unimodal (auditory or visual) and multimodal (audio-visual) stimuli. Univariate analyses revealed the recruitment of functionally distinct AnG subregions during the retrieval of episodic and semantic information. Consistent with a role in multimodal feature integration during episodic retrieval, significantly greater AnG activity was observed during retrieval of integrated multimodal episodic memories compared with unimodal episodic memories. Multivariate classification analyses revealed that individual multimodal episodic memories could be differentiated in AnG, with classification accuracy tracking the vividness of participants' reported recollections, whereas distinct unimodal memories were represented in sensory association areas only. In contrast to episodic retrieval, AnG was engaged to a statistically equivalent degree during retrieval of unimodal and multimodal semantic memories, suggesting a distinct role for AnG during semantic retrieval. Modality-specific sensory association areas exhibited corresponding activity during both episodic and semantic retrieval, which mirrored the functional specialization of these regions during perception. The results offer new insights into the integrative processes subserved by AnG and its contribution to our subjective experience of remembering. SIGNIFICANCE STATEMENT: Using univariate and multivariate fMRI analyses, we provide evidence that functionally distinct subregions of angular gyrus (AnG) contribute to the retrieval of episodic and semantic memories. Our multivariate pattern classifier could distinguish episodic memory representations in AnG according to whether they were multimodal (audio visual) or unimodal (auditory or visual) in nature, whereas statistically equivalent AnG activity was observed during retrieval of unimodal and multimodal semantic memories. Classification accuracy during episodic retrieval scaled with the trial-by-trial vividness with which participants experienced their recollections. Therefore, the findings offer new insights into the integrative processes subserved by AnG and how its function may contribute to our subjective experience of remembering. PMID- 27194329 TI - Less Is More: Semantic Information Survives Interocular Suppression When Attention Is Diverted. AB - The extent of unconscious semantic processing has been debated. It is well established that semantic information is registered in the absence of awareness induced by inattention. However, it has been debated whether semantic information of invisible stimuli is processed during interocular suppression, a procedure that renders one eye's view invisible by presenting a dissimilar stimulus to the other eye. Inspired by recent evidence demonstrating that reduced attention attenuates interocular suppression, we tested a counterintuitive hypothesis that attention withdrawn from the suppressed target location facilitates semantic processing in the absence of awareness induced by interocular suppression. We obtained an electrophysiological marker of semantic processing (N400 component) while human participants' spatial attention was being manipulated with a cueing paradigm during interocular suppression. We found that N400 modulation was absent when participants' attention was directed to the target location, but present when diverted elsewhere. In addition, the correlation analysis across participants indicated that the N400 amplitude was reduced with more attention being directed to the target location. Together, these results indicate that inattention attenuates interocular suppression and thereby makes semantic processing available unconsciously, reconciling conflicting evidence in the literature. We discuss a tight link among interocular suppression, attention, and conscious awareness. SIGNIFICANCE STATEMENT: Interocular suppression offers a powerful means of studying the extent of unconscious processing by rendering a salient stimulus presented to one eye invisible. Here, we provide evidence that attention is a determining factor for unconscious semantic processing. An electrophysiological marker for semantic processing (N400 component) was present when attention was diverted away from the suppressed stimulus but absent when attention was directed to that stimulus, indicating that inattention facilitates unconscious semantic processing during the interocular suppression. Although contrary to the common sense assumption that attention facilitates information processing, this result is in accordance with recent studies showing that attention modulates interocular suppression but is not necessary for semantic processing. Our finding reconciles the conflicting evidence and advances theories of consciousness. PMID- 27194328 TI - Npas1+ Pallidal Neurons Target Striatal Projection Neurons. AB - Compelling evidence demonstrates that the external globus pallidus (GPe) plays a key role in processing sensorimotor information. An anatomical projection from the GPe to the dorsal striatum has been described for decades. However, the cellular target and functional impact of this projection remain unknown. Using cell-specific transgenic mice, modern monosynaptic tracing techniques, and optogenetics-based mapping, we discovered that GPe neurons provide inhibitory inputs to direct and indirect pathway striatal projection neurons (SPNs). Our results indicate that the GPe input to SPNs arises primarily from Npas1 expressing neurons and is strengthened in a chronic Parkinson's disease (PD) model. Alterations of the GPe-SPN input in a PD model argue for the critical position of this connection in regulating basal ganglia motor output and PD symptomatology. Finally, chemogenetic activation of Npas1-expressing GPe neurons suppresses motor output, arguing that strengthening of the GPe-SPN connection is maladaptive and may underlie the hypokinetic symptoms in PD. SIGNIFICANCE STATEMENT: An anatomical projection from the pallidum to the striatum has been described for decades, but little is known about its connectivity pattern. The authors dissect the presynaptic and postsynaptic neurons involved in this projection, and show its cell-specific remodeling and strengthening in parkinsonian mice. Chemogenetic activation of Npas1(+) pallidal neurons that give rise to the principal pallidostriatal projection increases the time that the mice spend motionless. This argues that maladaptive strengthening of this connection underlies the paucity of volitional movements, which is a hallmark of Parkinson's disease. PMID- 27194330 TI - Opiates Modulate Noxious Chemical Nociception through a Complex Monoaminergic/Peptidergic Cascade. AB - The ability to detect noxious stimuli, process the nociceptive signal, and elicit an appropriate behavioral response is essential for survival. In Caenorhabditis elegans, opioid receptor agonists, such as morphine, mimic serotonin, and suppress the overall withdrawal from noxious stimuli through a pathway requiring the opioid-like receptor, NPR-17. This serotonin- or morphine-dependent modulation can be rescued in npr-17-null animals by the expression of npr-17 or a human kappa opioid receptor in the two ASI sensory neurons, with ASI opioid signaling selectively inhibiting ASI neuropeptide release. Serotonergic modulation requires peptides encoded by both nlp-3 and nlp-24, and either nlp-3 or nlp-24 overexpression mimics morphine and suppresses withdrawal. Peptides encoded by nlp-3 act differentially, with only NLP-3.3 mimicking morphine, whereas other nlp-3 peptides antagonize NLP-3.3 modulation. Together, these results demonstrate that opiates modulate nociception in Caenorhabditis elegans through a complex monoaminergic/peptidergic cascade, and suggest that this model may be useful for dissecting opiate signaling in mammals. SIGNIFICANCE STATEMENT: Opiates are used extensively to treat chronic pain. In Caenorhabditis elegans, opioid receptor agonists suppress the overall withdrawal from noxious chemical stimuli through a pathway requiring an opioid-like receptor and two distinct neuropeptide-encoding genes, with individual peptides from the same gene functioning antagonistically to modulate nociception. Endogenous opioid signaling functions as part of a complex, monoaminergic/peptidergic signaling cascade and appears to selectively inhibit neuropeptide release, mediated by a alpha adrenergic-like receptor, from two sensory neurons. Importantly, receptor null animals can be rescued by the expression of the human kappa opioid receptor, and injection of human opioid receptor ligands mimics exogenous opiates, highlighting the utility of this model for dissecting opiate signaling in mammals. PMID- 27194332 TI - Neural Coding of Interaural Time Differences with Bilateral Cochlear Implants in Unanesthetized Rabbits. AB - Although bilateral cochlear implants (CIs) provide improvements in sound localization and speech perception in noise over unilateral CIs, bilateral CI users' sensitivity to interaural time differences (ITDs) is still poorer than normal. In particular, ITD sensitivity of most CI users degrades with increasing stimulation rate and is lacking at the high carrier pulse rates used in CI processors to deliver speech information. To gain a better understanding of the neural basis for this degradation, we characterized ITD tuning of single neurons in the inferior colliculus (IC) for pulse train stimuli in an unanesthetized rabbit model of bilateral CIs. Approximately 73% of IC neurons showed significant ITD sensitivity in their overall firing rates. On average, ITD sensitivity was best for pulse rates near 80-160 pulses per second (pps) and degraded for both lower and higher pulse rates. The degradation in ITD sensitivity at low pulse rates was caused by strong, unsynchronized background activity that masked stimulus-driven responses in many neurons. Selecting synchronized responses by temporal windowing revealed ITD sensitivity in these neurons. With temporal windowing, both the fraction of ITD-sensitive neurons and the degree of ITD sensitivity decreased monotonically with increasing pulse rate. To compare neural ITD sensitivity to human performance in ITD discrimination, neural just noticeable differences (JNDs) in ITD were computed using signal detection theory. Using temporal windowing at lower pulse rates, and overall firing rate at higher pulse rates, neural ITD JNDs were within the range of perceptual JNDs in human CI users over a wide range of pulse rates. SIGNIFICANCE STATEMENT: Many profoundly deaf people wearing cochlear implants (CIs) still face challenges in everyday situations, such as understanding conversations in noise. Even with CIs in both ears, they have difficulty making full use of subtle differences in the sounds reaching the two ears [interaural time difference (ITD)] to identify where the sound is coming from. This problem is especially acute at the high stimulation rates used in clinical CI processors. This study provides a better understanding of ITD processing with bilateral CIs and shows a parallel between human performance in ITD discrimination and neural responses in the auditory midbrain. The present study is the first report on binaural properties of auditory neurons with CIs in unanesthetized animals. PMID- 27194331 TI - Identification of a Circadian Clock in the Inferior Colliculus and Its Dysregulation by Noise Exposure. AB - Circadian rhythms regulate bodily functions within 24 h and long-term disruptions in these rhythms can cause various diseases. Recently, the peripheral auditory organ, the cochlea, has been shown to contain a self-sustained circadian clock that regulates differential sensitivity to noise exposure throughout the day. Animals exposed to noise during the night are more vulnerable than when exposed during the day. However, whether other structures throughout the auditory pathway also possess a circadian clock remains unknown. Here, we focus on the inferior colliculus (IC), which plays an important role in noise-induced pathologies such as tinnitus, hyperacusis, and audiogenic seizures. Using PER2::LUC transgenic mice and real-time bioluminescence recordings, we revealed circadian oscillations of Period 2 protein in IC explants for up to 1 week. Clock genes (Cry1, Bmal1, Per1, Per2, Rev-erbalpha, and Dbp) displayed circadian molecular oscillations in the IC. Averaged expression levels of early-induced genes and clock genes during 24 h revealed differential responses to day or night noise exposure. Rev-erbalpha and Dbp genes were affected only by day noise exposure, whereas Per1 and Per2 were affected only by night noise exposure. However, the expression of Bdnf was affected by both day and night noise exposure, suggesting that plastic changes are unlikely to be involved in the differences in day or night noise sensitivity in the IC. These novel findings highlight the importance of circadian responses in the IC and emphasize the importance of circadian mechanisms for understanding central auditory function and disorders. SIGNIFICANCE STATEMENT: Recent findings identified the presence of a circadian clock in the inner ear. Here, we present novel findings that neurons in the inferior colliculus (IC), a central auditory relay structure involved in sound processing, express a circadian clock as evidenced at both the mRNA and protein levels. Using a reporter mouse that expresses a luciferase protein coupled to the core clock protein PERIOD2 (PER2::LUC), we could observe spontaneous circadian oscillations in culture. Furthermore, we reveal that the mRNA profile of clock-related genes in the IC is altered differentially by day or night noise exposure. The identification of a clock in the IC is relevant for understanding the mechanisms underlying dysfunctions of the IC such as tinnitus, hyperacusis, or audiogenic seizures. PMID- 27194334 TI - High Working Memory Load Increases Intracortical Inhibition in Primary Motor Cortex and Diminishes the Motor Affordance Effect. AB - Motor affordances occur when the visual properties of an object elicit behaviorally relevant motor representations. Typically, motor affordances only produce subtle effects on response time or on motor activity indexed by neuroimaging/neuroelectrophysiology, but sometimes they can trigger action itself. This is apparent in "utilization behavior," where individuals with frontal cortex damage inappropriately grasp affording objects. This raises the possibility that, in healthy-functioning individuals, frontal cortex helps ensure that irrelevant affordance provocations remain below the threshold for actual movement. In Experiment 1, we tested this "frontal control" hypothesis by "loading" the frontal cortex with an effortful working memory (WM) task (which ostensibly consumes frontal resources) and examined whether this increased EEG measures of motor affordances to irrelevant affording objects. Under low WM load, there were typical motor affordance signatures: an event-related desynchronization in the mu frequency and an increased P300 amplitude for affording (vs nonaffording) objects over centroparietal electrodes. Contrary to our prediction, however, these affordance measures were diminished under high WM load. In Experiment 2, we tested competing mechanisms responsible for the diminished affordance in Experiment 1. We used paired-pulse transcranial magnetic stimulation over primary motor cortex to measure long-interval cortical inhibition. We found greater long-interval cortical inhibition for high versus low load both before and after the affording object, suggesting that a tonic inhibition state in primary motor cortex could prevent the affordance from provoking the motor system. Overall, our results suggest that a high WM load "sets" the motor system into a suppressed state that mitigates motor affordances. SIGNIFICANCE STATEMENT: Is an irrelevant motor affordance more likely to be triggered when you are under low or high cognitive load? We examined this using physiological measures of the motor affordance while working memory load was varied. We observed a typical motor affordance signature when working memory load was low; however, it was abolished when load was high. Further, there was increased intracortical inhibition in primary motor cortex under high working memory load. This suggests that being in a state of high cognitive load "sets" the motor system to be imperturbable to distracting motor influences. This makes a novel link between working memory load and the balance of excitatory/inhibitory activity in the motor cortex and potentially has implications for disorders of impulsivity. PMID- 27194333 TI - Contour Curvature As an Invariant Code for Objects in Visual Area V4. AB - Size-invariant object recognition-the ability to recognize objects across transformations of scale-is a fundamental feature of biological and artificial vision. To investigate its basis in the primate cerebral cortex, we measured single neuron responses to stimuli of varying size in visual area V4, a cornerstone of the object-processing pathway, in rhesus monkeys (Macaca mulatta). Leveraging two competing models for how neuronal selectivity for the bounding contours of objects may depend on stimulus size, we show that most V4 neurons (~70%) encode objects in a size-invariant manner, consistent with selectivity for a size-independent parameter of boundary form: for these neurons, "normalized" curvature, rather than "absolute" curvature, provided a better account of responses. Our results demonstrate the suitability of contour curvature as a basis for size-invariant object representation in the visual cortex, and posit V4 as a foundation for behaviorally relevant object codes. SIGNIFICANCE STATEMENT: Size-invariant object recognition is a bedrock for many perceptual and cognitive functions. Despite growing neurophysiological evidence for invariant object representations in the primate cortex, we still lack a basic understanding of the encoding rules that govern them. Classic work in the field of visual shape theory has long postulated that a representation of objects based on information about their bounding contours is well suited to mediate such an invariant code. In this study, we provide the first empirical support for this hypothesis, and its instantiation in single neurons of visual area V4. PMID- 27194337 TI - Death Domain Signaling by Disulfide-Linked Dimers of the p75 Neurotrophin Receptor Mediates Neuronal Death in the CNS. AB - The p75 neurotrophin receptor (p75(NTR)) mediates neuronal death in response to neural insults by activating a caspase apoptotic pathway. The oligomeric state and activation mechanism that enable p75(NTR) to mediate these effects have recently been called into question. Here, we have investigated mutant mice lacking the p75(NTR) death domain (DD) or a highly conserved transmembrane (TM) cysteine residue (Cys(259)) implicated in receptor dimerization and activation. Neuronal death induced by proneurotrophins or epileptic seizures was assessed and compared with responses in p75(NTR) knock-out mice and wild-type animals. Proneurotrophins induced apoptosis of cultured hippocampal and cortical neurons from wild-type mice, but mutant neurons lacking p75(NTR), only the p75(NTR) DD, or just Cys(259) were all equally resistant to proneurotrophin-induced neuronal death. Homo-FRET anisotropy experiments demonstrated that both NGF and proNGF induce conformational changes in p75(NTR) that are dependent on the TM cysteine. In vivo, neuronal death induced by pilocarpine-mediated seizures was significantly reduced in the hippocampus and somatosensory, piriform, and entorhinal cortices of all three strains of p75(NTR) mutant mice. Interestingly, the levels of protection observed in mice lacking the DD or only Cys(259) were identical to those of p75(NTR) knock-out mice even though the Cys(259) mutant differed from the wild-type receptor in only one amino acid residue. We conclude that, both in vitro and in vivo, neuronal death induced by p75(NTR) requires the DD and TM Cys(259), supporting the physiological relevance of DD signaling by disulfide-linked dimers of p75(NTR) in the CNS. SIGNIFICANCE STATEMENT: A detailed understanding of the physiological significance of distinct structural determinants in the p75 neurotrophin receptor (p75(NTR)) is crucial for the identification of suitable drug targets in this receptor. We have tested the relevance of the p75(NTR) death domain (DD) and the highly conserved transmembrane residue Cys(259) for the ability of p75(NTR) to induce apoptosis in neurons of the CNS using gene-targeted mutant mice. The physiological importance of these determinants had been contested in some recent in vitro studies. Our results indicate a requirement for DD signaling by disulfide-linked dimers of p75(NTR) for neuronal death induced by proneurotrophins and epileptic seizures. These new mouse models will be useful for clarifying different aspects of p75(NTR) physiology. PMID- 27194335 TI - Pallidostriatal Projections Promote beta Oscillations in a Dopamine-Depleted Biophysical Network Model. AB - In the basal ganglia, focused rhythmicity is an important feature of network activity at certain stages of motor processing. In disease, however, the basal ganglia develop amplified rhythmicity. Here, we demonstrate how the cellular architecture and network dynamics of an inhibitory loop in the basal ganglia yield exaggerated synchrony and locking to beta oscillations, specifically in the dopamine-depleted state. A key component of this loop is the pallidostriatal pathway, a well-characterized anatomical projection whose function has long remained obscure. We present a synaptic characterization of this pathway in mice and incorporate these data into a computational model that we use to investigate its influence over striatal activity under simulated healthy and dopamine depleted conditions. Our model predicts that the pallidostriatal pathway influences striatal output preferentially during periods of synchronized activity within GPe. We show that, under dopamine-depleted conditions, this effect becomes a key component of a positive feedback loop between the GPe and striatum that promotes synchronization and rhythmicity. Our results generate novel predictions about the role of the pallidostriatal pathway in shaping basal ganglia activity in health and disease. SIGNIFICANCE STATEMENT: This work demonstrates that functional connections from the globus pallidus externa (GPe) to striatum are substantially stronger onto fast-spiking interneurons (FSIs) than onto medium spiny neurons. Our circuit model suggests that when GPe spikes are synchronous, this pallidostriatal pathway causes synchronous FSI activity pauses, which allow a transient window of disinhibition for medium spiny neurons. In simulated dopamine-depletion, this GPe-FSI activity is necessary for the emergence of strong synchronization and the amplification and propagation of beta oscillations, which are a hallmark of parkinsonian circuit dysfunction. These results suggest that GPe may play a central role in propagating abnormal circuit activity to striatum, which in turn projects to downstream basal ganglia structures. These findings warrant further exploration of GPe as a target for interventions for Parkinson's disease. PMID- 27194336 TI - Progressive Changes in a Distributed Neural Circuit Underlie Breathing Abnormalities in Mice Lacking MeCP2. AB - Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in Methyl-CpG-binding protein 2 (MECP2). Severe breathing abnormalities are common in RTT and are reproduced in mouse models of RTT. Previously, we found that removing MeCP2 from the brainstem and spinal cord in mice caused early lethality and abnormal breathing. To determine whether loss of MeCP2 in functional components of the respiratory network causes specific breathing disorders, we used the Cre/LoxP system to differentially manipulate MeCP2 expression throughout the brainstem respiratory network, specifically within HoxA4-derived tissues, which include breathing control circuitry within the nucleus tractus solitarius and the caudal part of ventral respiratory column but do not include more rostral parts of the breathing control circuitry. To determine whether respiratory phenotypes manifested in animals with MeCP2 removed from specific pons medullary respiratory circuits, we performed whole-body plethysmography and electrophysiological recordings from in vitro brainstem slices from mice lacking MeCP2 in different circuits. Our results indicate that MeCP2 expression in the medullary respiratory network is sufficient for normal respiratory rhythm and preventing apnea. However, MeCP2 expression within components of the breathing circuitry rostral to the HoxA4 domain are neither sufficient to prevent the hyperventilation nor abnormal hypoxic ventilatory response. Surprisingly, we found that MeCP2 expression in the HoxA4 domain alone is critical for survival. Our study reveals that MeCP2 is differentially required in select respiratory components for different aspects of respiratory functions, and collectively for the integrity of this network functions to maintain proper respiration. SIGNIFICANCE STATEMENT: Breathing abnormalities are a significant clinical feature in Rett syndrome and are robustly reproduced in the mouse models of this disease. Previous work has established that alterations in the function of MeCP2, the protein encoded by the gene mutated in Rett syndrome, within the hindbrain are critical for control of normal breathing. Here we show that MeCP2 function plays distinct roles in specific brainstem regions in the genesis of various aspects of abnormal breathing. This provides insight into the pathogenesis of these breathing abnormalities in Rett syndrome, which could be used to target treatments to improve these symptoms. Furthermore, it provides further knowledge about the fundamental neural circuits that control breathing. PMID- 27194320 TI - Capillary blood islet autoantibody screening for identifying pre-type 1 diabetes in the general population: design and initial results of the Fr1da study. AB - INTRODUCTION: Type 1 diabetes can be diagnosed at an early presymptomatic stage by the detection of islet autoantibodies. The Fr1da study aims to assess whether early staging of type 1 diabetes (1) is feasible at a population-based level, (2) prevents severe metabolic decompensation observed at the clinical manifestation of type 1 diabetes and (3) reduces psychological distress through preventive teaching and care. METHODS AND ANALYSIS: Children aged 2-5 years in Bavaria, Germany, will be tested for the presence of multiple islet autoantibodies. Between February 2015 and December 2016, 100 000 children will be screened by primary care paediatricians. Islet autoantibodies are measured in capillary blood samples using a multiplex three-screen ELISA. Samples with ELISA results >97.5th centile are retested using reference radiobinding assays. A venous blood sample is also obtained to confirm the autoantibody status of children with at least two autoantibodies. Children with confirmed multiple islet autoantibodies are diagnosed with pre-type 1 diabetes. These children and their parents are invited to participate in an education and counselling programme at a local diabetes centre. Depression and anxiety, and burden of early diagnosis are also assessed. RESULTS: Of the 1027 Bavarian paediatricians, 39.3% are participating in the study. Overall, 26 760 children have been screened between February 2015 and November 2015. Capillary blood collection was sufficient in volume for islet autoantibody detection in 99.46% of the children. The remaining 0.54% had insufficient blood volume collected. Of the 26 760 capillary samples tested, 0.39% were positive for at least two islet autoantibodies. DISCUSSION: Staging for early type 1 diabetes within a public health setting appears to be feasible. The study may set new standards for the early diagnosis of type 1 diabetes and education. ETHICS DISSEMINATION: The study was approved by the ethics committee of Technische Universitat Munchen (Nr. 70/14). PMID- 27194339 TI - Pathogenic Upregulation of Glial Lipocalin-2 in the Parkinsonian Dopaminergic System. AB - Lipocalin-2 (LCN2) is a member of the highly heterogeneous secretory protein family of lipocalins and increases in its levels can contribute to neurodegeneration in the adult brain. However, there are no reports on the role of LCN2 in Parkinson's disease (PD). Here, we report for the first time that LCN2 expression is increased in the substantia nigra (SN) of patients with PD. In mouse brains, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment for a neurotoxin model of PD significantly upregulated LCN2 expression, mainly in reactive astrocytes in both the SN and striatum. The increased LCN2 levels contributed to neurotoxicity and neuroinflammation, resulting in disruption of the nigrostriatal dopaminergic (DA) projection and abnormal locomotor behaviors, which were ameliorated in LCN2-deficient mice. Similar to the effects of MPTP treatment, LCN2-induced neurotoxicity was also observed in the 6-hydroxydopamine (6-OHDA)-treated animal model of PD. Moreover, treatment with the iron donor ferric citrate (FC) and the iron chelator deferoxamine mesylate (DFO) increased and decreased, respectively, the LCN2-induced neurotoxicity in vivo In addition to the in vivo results, 1-methyl-4-phenylpyridinium (MPP(+))-induced neurotoxicity in cocultures of mesencephalic neurons and astrocytes was reduced by LCN2 gene deficiency in the astrocytes and conditioned media derived from MPP(+)-treated SH-SY5Y neuronal enhanced glial expression of LCN2 in vitro Therefore, our results demonstrate that astrocytic LCN2 upregulation in the lesioned DA system may play a role as a potential pathogenic factor in PD and suggest that inhibition of LCN2 expression or activity may be useful in protecting the nigrostriatal DA system in the adult brain. SIGNIFICANCE STATEMENT: Lipocalin-2 (LCN2), a member of the highly heterogeneous secretory protein family of lipocalins, may contribute to neuroinflammation and neurotoxicity in the brain. However, LCN2 expression and its role in Parkinson's disease (PD) are largely unknown. Here, we report that LCN2 is upregulated in the substantia nigra of patients with PD and neurotoxin-treated animal models of PD. Our results suggest that LCN2 upregulation might be a potential pathogenic mechanism of PD, which would result in disruption of the nigrostriatal dopaminergic system through neurotoxic iron accumulation and neuroinflammation. Therefore, inhibition of LCN2 expression or activity may be useful in protecting the nigrostriatal dopaminergic projection in PD. PMID- 27194340 TI - Superior Intraparietal Sulcus Controls the Variability of Visual Working Memory Precision. AB - Limitations of working memory (WM) capacity depend strongly on the cognitive resources that are available for maintaining WM contents in an activated state. Increasing the number of items to be maintained in WM was shown to reduce the precision of WM and to increase the variability of WM precision over time. Although WM precision was recently associated with neural codes particularly in early sensory cortex, we have so far no understanding of the neural bases underlying the variability of WM precision, and how WM precision is preserved under high load. To fill this gap, we combined human fMRI with computational modeling of behavioral performance in a delayed color-estimation WM task. Behavioral results replicate a reduction of WM precision and an increase of precision variability under high loads (5 > 3 > 1 colors). Load-dependent BOLD signals in primary visual cortex (V1) and superior intraparietal sulcus (IPS), measured during the WM task at 2-4 s after sample onset, were modulated by individual differences in load-related changes in the variability of WM precision. Although stronger load-related BOLD increase in superior IPS was related to lower increases in precision variability, thus stabilizing WM performance, the reverse was observed for V1. Finally, the detrimental effect of load on behavioral precision and precision variability was accompanied by a load related decline in the accuracy of decoding the memory stimuli (colors) from left superior IPS. We suggest that the superior IPS may contribute to stabilizing visual WM performance by reducing the variability of memory precision in the face of higher load. SIGNIFICANCE STATEMENT: This study investigates the neural bases of capacity limitations in visual working memory by combining fMRI with cognitive modeling of behavioral performance, in human participants. It provides evidence that the superior intraparietal sulcus (IPS) is a critical brain region that influences the variability of visual working memory precision between and within individuals (Fougnie et al., 2012; van den Berg et al., 2012) under increased memory load, possibly in cooperation with perceptual systems of the occipital cortex. These findings substantially extend our understanding of the nature of capacity limitations in visual working memory and their neural bases. Our work underlines the importance of integrating cognitive modeling with univariate and multivariate methods in fMRI research, thus improving our knowledge of brain behavior relationships. PMID- 27194341 TI - Cyclic Nucleotide Control of Microtubule Dynamics for Axon Guidance. AB - Graded distribution of intracellular second messengers, such as Ca(2+) and cyclic nucleotides, mediates directional cell migration, including axon navigational responses to extracellular guidance cues, in the developing nervous system. Elevated concentrations of cAMP or cGMP on one side of the neuronal growth cone induce its attractive or repulsive turning, respectively. Although effector processes downstream of Ca(2+) have been extensively studied, very little is known about the mechanisms that enable cyclic nucleotides to steer migrating cells. Here, we show that asymmetric cyclic nucleotide signaling across the growth cone mediates axon guidance via modulating microtubule dynamics and membrane organelle transport. In embryonic chick dorsal root ganglion neurons in culture, contact of an extending microtubule with the growth cone leading edge induces localized membrane protrusion at the site of microtubule contact. Such a contact-induced protrusion requires exocytosis of vesicle-associated membrane protein 7 (VAMP7)-positive vesicles that have been transported centrifugally along the microtubule. We found that the two cyclic nucleotides counteractively regulate the frequency of microtubule contacts and targeted delivery of VAMP7 vesicles: cAMP stimulates and cGMP inhibits these events, thereby steering the growth cone in the opposite directions. By contrast, Ca(2+) signals elicit no detectable change in either microtubule contacts or VAMP7 vesicle delivery during Ca(2+)-induced growth cone turning. Our findings clearly demonstrate growth cone steering machinery downstream of cyclic nucleotide signaling and highlight a crucial role of dynamic microtubules in leading-edge protrusion for cell chemotaxis. SIGNIFICANCE STATEMENT: Developing neurons can extend long axons toward their postsynaptic targets. The tip of each axon, called the growth cone, recognizes extracellular guidance cues and navigates the axon along the correct path. Here we show that asymmetric cyclic nucleotide signaling across the growth cone mediates axon guidance through localized regulation of microtubule dynamics and resulting recruitment of specific populations of membrane vesicles to the growth cone's leading edge. Remarkably, cAMP stimulates microtubule growth and membrane protrusion, whereas cGMP promotes microtubule retraction and membrane senescence, explaining the opposite directional polarities of growth cone turning induced by these cyclic nucleotides. This study reveals a novel microtubule-based mechanism through which cyclic nucleotides polarize the growth cone steering machinery for bidirectional axon guidance. PMID- 27194338 TI - Sensory Cortical Activity Is Related to the Selection of a Rhythmic Motor Action Pattern. AB - Rats produce robust, highly distinctive orofacial rhythms in response to taste stimuli-responses that aid in the consumption of palatable tastes and the ejection of aversive tastes, and that are sourced in a multifunctional brainstem central pattern generator. Several pieces of indirect evidence suggest that primary gustatory cortex (GC) may be a part of a distributed forebrain circuit involved in the selection of particular consumption-related rhythms, although not in the production of individual mouth movements per se. Here, we performed a series of tests of this hypothesis. We first examined the temporal relationship between GC activity and orofacial behaviors by performing paired single-neuron and electromyographic recordings in awake rats. Using a trial-by-trial analysis, we found that a subset of GC neurons shows a burst of activity beginning before the transition between nondistinct and taste-specific (i.e., consumption-related) orofacial rhythms. We further showed that shifting the latency of consumption related behavior by selective cueing has an analogous impact on the timing of GC activity. Finally, we showed the complementary result, demonstrating that optogenetic perturbation of GC activity has a modest but significant impact on the probability that a specific rhythm will be produced in response to a strongly aversive taste. GC appears to be a part of a distributed circuit that governs the selection of taste-induced orofacial rhythms. SIGNIFICANCE STATEMENT: In many well studied (typically invertebrate) sensorimotor systems, top-down modulation helps motor-control regions "select" movement patterns. Here, we provide evidence that gustatory cortex (GC) may be part of the forebrain circuit that performs this function in relation to oral behaviors ("gapes") whereby a substance in the mouth is rejected as unpalatable. We show that GC palatability coding is well timed to play this role, and that the latency of these codes changes as the latency of gaping shifts with learning. We go on to show that by silencing these neurons, we can change the likelihood of gaping. These data help to break down the sensory/motor divide by showing a role for sensory cortex in the selection of motor behavior. PMID- 27194342 TI - Age Is Associated with Reduced Sharp-Wave Ripple Frequency and Altered Patterns of Neuronal Variability. AB - Spatial and episodic memory performance declines with age, and the neural basis for this decline is not well understood. Sharp-wave ripples are brief (~70 ms) high-frequency oscillatory events generated in the hippocampus and are associated with the consolidation of spatial memories. Given the connection between ripple oscillations and memory consolidation, we investigated whether the structure of ripple oscillations and ripple-triggered patterns of single-unit activity are altered in aged rats. Local field and single-unit activity surrounding sharp-wave ripple events were examined in the CA1 region of the hippocampus of old (n = 5) and young (n = 6) F344 rats during periods of rest preceding and following performance on a place-dependent eyeblink-conditioning task. Neural responses in aged rats differed from responses in young rats in several ways. First, compared with young rats, the rate of ripple occurrence (ripple density) is reduced in aged rats during postbehavior rest. Second, mean ripple frequency during prebehavior and postbehavior rest is lower in aged animals (aged: 132 Hz; young: 146 Hz). Third, single neurons in aged animals responded more consistently from ripple to ripple. Fourth, variability in interspike intervals was greater in aged rats. Finally, neurons were tuned to a narrower range of phases of the ripple oscillation relative to young animals. Together, these results suggest that the CA1 network in aged animals has a reduced "vocabulary" of available representational states. SIGNIFICANCE STATEMENT: The hippocampus is a structure that is critical for the formation of episodic memories. Sharp-wave ripple events generated in the hippocampus have been implicated in memory consolidation processes critical to memory stabilization. We examine here whether these ripple oscillations are altered over the course of the life span, which could contribute to hippocampus-dependent memory deficits that occur during aging. This experiment used young and aged memory-impaired rats to examine age-related changes in ripple architecture, ripple-triggered spike variance, and spike-phase coherence. We found that there are, indeed, significant changes in characteristics of ripples in older animals that could impact consolidation processes and memory stabilization in the aged brain. PMID- 27194343 TI - Dopamine D1-like Receptors Regulate Constitutive, MU-Opioid Receptor-Mediated Repression of Use-Dependent Synaptic Plasticity in Dorsal Horn Neurons: More Harm than Good? AB - The current study reports on a synaptic mechanism through which D1-like receptors (D1LRs) modulate spinal nociception and plasticity by regulating activation of the MU-opioid receptor (MOR).D1LR stimulation with agonist SKF 38393 concentration-dependently depressed C-fiber-evoked potentials in rats receiving spinal nerve ligation (SNL), but not in uninjured rats. Depression was prevented by MOR- but not GABA-receptor blockade. Neurons expressing the D1 subtype were immunopositive for met-enkephalin and vesicular glutamate transporter VGLUT2, but not for GABAergic marker vGAT.Nerve ligation was followed by increased immunoreactivity for D1 in synaptic compartment (P3) in dorsal horn homogenates and presynaptic met-enkephalin-containing boutons. SNL led to increased immunoreactivity for met-enkephalin in dorsal horn homogenates, which was dose dependently attenuated by selective D1LR antagonist SCH 23390. During blockade of either D1R or MOR, low-frequency (0.2 or 3 Hz) stimulation (LFS) to the sciatic nerve induced long-term potentiation (LTP) of C-fiber-evoked potentials, revealing a constituent role of both receptors in repressing afferent-induced synaptic plasticity. LFS consistently induced NMDA receptor-dependent LTP in nerve-injured rats. The ability of MOR both to prevent LTP and to modulate mechanical and thermal pain thresholds in behavioral tests was preserved in nerve ligated rats that were postoperatively treated with SCH 23390. D1LR priming for 30 min sufficed to disrupt MOR function in otherwise naive rats via a mechanism involving receptor overuse.The current data support that, whereas D1LR-modulated MOR activation is instrumental in antinociception and endogenous repression of synaptic plasticity, this mechanism deteriorates rapidly by sustained use, generating increased vulnerability to afferent input. SIGNIFICANCE STATEMENT: The current study shows that dopamine D1-like receptors (D1LRs) and MU-opioid receptors (MOR) in the spinal dorsal horn constitutively repress the expression of synaptic long-term potentiation (LTP) of C-fiber-evoked potentials. Anatomical data are provided supporting that the D1 subtype regulates MOR function by modulating met-enkephalin release. Sustained neuropathic pain induced by spinal nerve ligation is accompanied by D1R and met-enkephalin upregulation, acquired D1LR-mediated antinociception, and a loss of endogenous repression of further synaptic plasticity. We show that the ability of MOR to oppose LTP is rapidly impaired by sustained D1LR activation via a mechanism involving sustained MOR activation. PMID- 27194344 TI - In vitro assessment of the combined effect of eicosapentaenoic acid, green tea extract and curcumin C3 on protein loss in C2C12 myotubes. AB - EPA has been clinically shown to reduce muscle wasting during cancer cachexia. This study investigates whether curcumin or green tea extract (GTE) enhances the ability of low doses of eicosapentaenoic acid (EPA) to reduce loss of muscle protein in an in vitro model. A low dose of EPA with minimal anti-cachectic activity was chosen to evaluate any potential synergistic effect with curcumin or GTE. Depression of protein synthesis and increase in degradation was determined in C2C12 myotubes in response to tumour necrosis factor-alpha (TNF-alpha) and proteolysis-inducing factor (PIF). EPA (50 MUM) or curcumin (10 MUg ml(-1)) alone had little effect on protein degradation caused by PIF but the combination produced complete inhibition, as did the combination with GTE (10 MUg ml(-1)). In response to TNF-alpha (25 ng ml(-1))-induced protein degradation, EPA had a small, but not significant effect on protein degradation; however, when curcumin and GTE were combined with EPA, the effect was enhanced. EPA completely attenuated the depression of protein synthesis caused by TNF-alpha, but not that caused by PIF. The combination of EPA with curcumin produced a significant increase in protein synthesis to both agents. GTE alone or in combination with EPA had no effect on the depression of protein synthesis by TNF-alpha, but did significantly increase protein synthesis in PIF-treated cells. Both TNF-alpha and PIF significantly reduced myotube diameter from 17 to 13 MUm for TNF-alpha (23.5%) and 15 MUm (11.8%) for PIF However the triple combination of EPA, curcumin and GTE returned diameters to values not significantly different from the control. These results suggest that either curcumin or GTE or the combination could enhance the anti-catabolic effect of EPA on lean body mass. PMID- 27194345 TI - Idiosyncratic phenomena during the spontaneous healing of traumatic tympanic membrane perforations. PMID- 27194346 TI - Insertion characteristics and placement of the Mid-Scala electrode array in human temporal bones using detailed cone beam computed tomography. AB - The aim of this study was to evaluate the insertion results and placement of the new Advanced Bionics HiFocus Mid-Scala (HFms) electrode array, inserted through the round window membrane, in eight fresh human temporal bones using cone beam computed tomography (CBCT). Pre- and post-insertion CBCT scans were registered to create a 3D reconstruction of the cochlea with the array inserted. With an image fusion technique both the bony edges of the cochlea and the electrode array in situ could accurately be determined, thus enabling to identify the exact position of the electrode array within the scala tympani. Vertical and horizontal scalar location was measured at four points along the cochlea base at an angular insertion depth of 90 degrees , 180 degrees and 270 degrees and at electrode 16, the most basal electrode. Smooth insertion through the round window membrane was possible in all temporal bones. The imaging results showed that there were no dislocations from the scala tympani into the scala vestibule. The HFms electrode was positioned in the middle of the scala along the whole electrode array in three out of the eight bones and in 62 % of the individual locations measured along the base of the cochlea. In only one cochlea a close proximity of the electrode with the basilar membrane was observed, indicating possible contact with the basilar membrane. The results and assessments presented in this study appear to be highly accurate. Although a further validation including histopathology is needed, the image fusion technique described in this study represents currently the most accurate method for intracochlear electrode assessment obtainable with CBCT. PMID- 27194347 TI - The Acrosome Reaction: A Historical Perspective. AB - Acrosome reaction is often referred to as acrosomal exocytosis, but it differs significantly from normal exocytosis. While the vesicle membrane initially holding excreting molecules remains on the cell surface during exocytosis, the outer acrosomal membrane and plasma membrane are lost by forming vesicles during acrosome reaction. In this context, the latter process resembles a release of exosome. However, recent experimental data indicate that the most important roles of acrosome reaction lie not in the release of acrosomal contents (or "vesiculated" plasma and outer acrosomal membrane complexes) but rather in changes in sperm membrane. This review describes the mechanism of fertilization vis-a-vis sperm membrane change, with a brief historical overview of the half century study of acrosome reaction. PMID- 27194349 TI - Role of Ion Channels in the Sperm Acrosome Reaction. AB - The acrosome reaction (AR) is a unique exocytotic process where the acrosome, a single membrane-delimited specialized organelle, overlying the nucleus in the sperm head of many species, fuses with the overlying plasma membrane. This reaction, triggered by physiological inducers from the female gamete, its vicinity, or other stimuli, discharges the acrosomal content modifying the plasma membrane, incorporating the inner acrosomal membrane, and exposing it to the extracellular medium. The AR is essential for sperm-egg coat penetration, fusion with the eggs' plasma membrane, and fertilization. As in most exocytotic processes Ca(2+) is crucial for the AR, as well as intracellular pH and membrane potential changes. Thus, among the required processes needed for this reaction, ion permeability changes involving channels are pivotal. In spite of the key role ion channels play in the AR, their identity and regulation is not fully understood. Though molecular and pharmacological evidence indicates that various ionic channels participate during the AR, such as store-operated Ca(2+) channels and voltage-dependent Ca(2+) channels, whole cell patch clamp recordings have failed to detect some of them until now. Since sperm display a very high resistance and a minute cytoplasmic volume, very few channels are needed to achieve large membrane potential and concentration changes. Functional detection of few channels in the morphologically complex and tiny sperm poses technical problems, especially when their conductance is very small, as in the case of SOCs. Single channel recordings and novel fluorescence microscopy strategies will help to define the participation of ionic channels in the intertwined signaling network that orchestrates the AR. PMID- 27194348 TI - The Acrosomal Matrix. AB - The acrosome, a single exocytotic vesicle on the head of sperm, has an essential role in fertilization, but the exact mechanisms by which it facilitates sperm-egg interactions remain unresolved. The acrosome contains dozens of secretory proteins that are packaged into the forming structure during spermatogenesis; many of these proteins are localized into specific topographical areas of the acrosome, while others are more diffusely distributed. Acrosomal proteins can also be biochemically classified as components of the acrosomal matrix, a large, relatively insoluble complex, or as soluble proteins. This review focuses on recent findings using genetically modified mice (gene knockouts and transgenic "green acrosome" mice) to study the effects of eliminating acrosomal matrix associated proteins on sperm structure and function. Some gene knockouts produce infertile phenotypes with obviously missing, specific activities that affect acrosome biogenesis during spermatogenesis or interfere with acrosome function in mature sperm. Mutations that delete some components produce fertile phenotypes with subtler effects that provide useful insights into acrosomal matrix function in fertilization. In general, these studies enable the reassessment of paradigms to explain acrosome formation and function and provide novel, objective insights into the roles of acrosomal matrix proteins in fertilization. The use of genetically engineered mouse models has yielded new mechanistic information that complements recent, important in vivo imaging studies. PMID- 27194350 TI - The Molecules of Sperm Exocytosis. AB - Exocytosis is a fundamental process used by eukaryotic cells to release biological compounds and to insert lipids and proteins in the plasma membrane. Specialized secretory cells undergo regulated exocytosis in response to physiological signals. Sperm exocytosis or acrosome reaction (AR) is essentially a regulated secretion with special characteristics. We will focus here on some of these unique features, covering the topology, kinetics, and molecular mechanisms that prepare, drive, and regulate membrane fusion during the AR. Last, we will compare acrosomal release with exocytosis in other model systems. PMID- 27194351 TI - Sperm Capacitation and Acrosome Reaction in Mammalian Sperm. AB - Physiological changes that endow mammalian sperm with fertilizing capacity are known as sperm capacitation. As part of capacitation, sperm develop an asymmetrical flagellar beating known as hyperactivation and acquire the ability to undergo the acrosome reaction. Together, these processes promote fertilizing competence in sperm. At the molecular level, capacitation involves a series of signal transduction events which include activation of cAMP-dependent phosphorylation pathways, removal of cholesterol, hyperpolarization of the sperm plasma membrane, and changes in ion permeability. In recent years, new technologies have aided in the study of sperm signaling molecules with better resolution, at both spatial and temporal levels, unraveling how different cascades integrate and cooperate to render a fertilizing sperm. Despite this new information, the molecular mechanisms connecting capacitation with acrosomal exocytosis and hyperactivation are not well understood. This review brings together results obtained in mammalian species in the field of sperm capacitation with special focus on those pathways involved in the preparation to undergo the acrosomal reaction. PMID- 27194352 TI - Lipid Regulation of Acrosome Exocytosis. AB - Lipids are critical regulators of mammalian sperm function, first helping prevent premature acrosome exocytosis, then enabling sperm to become competent to fertilize at the right place/time through the process of capacitation, and ultimately triggering acrosome exocytosis. Yet because they do not fit neatly into the "DNA--RNA-protein" synthetic pathway, they are understudied and poorly understood. Here, we focus on three lipids or lipid classes-cholesterol, phospholipids, and the ganglioside G(M1)--in context of the modern paradigm of acrosome exocytosis. We describe how these various- species are precisely segregated into membrane macrodomains and microdomains, simultaneously preventing premature exocytosis while acting as foci for organizing regulatory and effector molecules that will enable exocytosis. Although the mechanisms responsible for these domains are poorly defined, there is substantial evidence for their composition and functions. We present diverse ways that lipids and lipid modifications regulate capacitation and acrosome exocytosis, describing in more detail how removal of cholesterol plays a master regulatory role in enabling exocytosis through at least two complementary pathways. First, cholesterol efflux leads to proteolytic activation of phospholipase B, which cleaves both phospholipid tails. The resultant changes in membrane curvature provide a mechanism for the point fusions now known to occur far before a sperm physically interacts with the zona pellucida. Cholesterol efflux also enables G(M1) to regulate the voltage-dependent cation channel, Ca(V)2.3, triggering focal calcium transients required for acrosome exocytosis in response to subsequent whole-cell calcium rises. We close with a model integrating functions for lipids in regulating acrosome exocytosis. PMID- 27194353 TI - Role of Actin Cytoskeleton During Mammalian Sperm Acrosomal Exocytosis. AB - Mammalian sperm require to undergo an exocytotic process called acrosomal exocytosis in order to be able to fuse with the oocyte. This ability is acquired during the course of sperm capacitation. This review is focused on one aspect related to this acquisition: the role of the actin cytoskeleton. Evidence from different laboratories indicates that actin polymerization occurs during capacitation, and the detection of several actin-related proteins suggests that the cytoskeleton is involved in important sperm functions. In other mammalian cells, the cortical actin network acts as a dominant negative clamp which blocks constitutive exocytosis but, at the same time, is necessary to prepare the cell to undergo regulated exocytosis. Thus, F-actin stabilizes structures generated by exocytosis and supports the physiological progression of this process. Is this also the case in mammalian sperm? This review summarizes what is currently known about actin and its related proteins in the male gamete, with particular emphasis on their role in acrosomal exocytosis. PMID- 27194354 TI - Site of Mammalian Sperm Acrosome Reaction. AB - Until recently, no special attention has been paid to the question of the site of mammalian sperm acrosome reaction (AR) in the female reproductive tract. Because AR is an essential process that enables the spermatozoon to fertilize, it is generally believed that it occurs at a specific step during sperm-egg interaction. It is generally thought that "the site of action coincides with the site of commitment." Thus, understanding the roles of AR and acrosomal substances is needed to gain insight into the site of the sperm commitment to undergo AR. PMID- 27194355 TI - Acrosome Reaction as a Preparation for Gamete Fusion. AB - The acrosome reaction (AR) is a universal requisite for sperm-egg fusion. However, whereas through the animal kingdom fusion of spermatozoa with the egg plasma membrane occurs via the inner acrosomal membrane exposed after the AR, in eutherian mammals, gamete fusion takes place through a specialized region of the acrosome known as the equatorial segment (ES) which becomes fusogenic only after the AR is completed. This chapter focuses on the different molecular mechanisms involved in the acquisition of the fusogenicity of the ES after the AR. We provide an update of the knowledge about the proteins proposed to have a role in this process either by modifying cytoskeletal and/or membrane molecules or by relocalizing to the ES after the AR to subsequently participate in gamete fusion. PMID- 27194356 TI - Systematic Evaluation of Drug-Loaded Hydrogels for Application in Osteosarcoma Treatment. AB - This is a literature review of studies focusing on the preparation of hydrogels for use as oncological drug delivery systems in the treatment of osteosarcoma (OS). The databases of the US National Library of Medicine National Institutes of Health, Embase, OVID, and Cochrane Library, and the references of retrieved studies, were traced from 1843 to December 21, 2015, without language restrictions. The obtained data were evaluated by complementary statistical methods. Potentially relevant studies were found and included in the analysis. OS specific chemotherapeutic agents can be successfully embedded within the hydrogels and these drug-loaded hydrogels can be applied locally, rather than systemically, without organ tissue toxicity. Further, OS-specific drug-loaded hydrogels significantly increased tumor inhibition and decreased osteolysis and lung metastases. Drug-loaded hydrogels could be useful in the treatment of OS, although their development remains at the experimental phase. Following evaluation of their application in surgery and the completion of drug release kinetics studies, drug-loaded hydrogels could be tested on living mammals in large samples with the aim of applying these in clinical settings. In the future, development of such drug delivery systems and application of targeted approaches against osteosarcoma and other malignancies may render surgery, radiotherapy and chemotherapy unnecessary. PMID- 27194357 TI - H2020 and Beyond: Skip Discrepancy between Theory and Practice of Personalized Medicine. A Position Paper by the Italian Society of Personalized Medicine. AB - Many unsolved practical issues, from technical and scientific to ethical, legal and economic topics, are slowing down the translation of Personalized Medicine principles into medical practice. The Italian Society of Personalized Medicine exposes here its point of view, based on the real-world practice of precision medicine carried-out in Italian healthcare structures. PMID- 27194358 TI - Microfluidic Devices for Automation of Assays on Drosophila Melanogaster for Applications in Drug Discovery and Biological Studies. AB - Drug discovery is a long and expensive process, which usually takes 12-15 years and could cost up to ~$1 billion. Conventional drug discovery process starts with high throughput screening and selection of drug candidates that bind to specific target associated with a disease condition. However, this process does not consider whether the chosen candidate is optimal not only for binding but also for ease of administration, distribution in the body, effect of metabolism and associated toxicity if any. A holistic approach, using model organisms early in the drug discovery process to select drug candidates that are optimal not only in binding but also suitable for administration, distribution and are not toxic is now considered as a viable way for lowering the cost and time associated with the drug discovery process. However, the conventional drug discovery assays using Drosophila are manual and required skill operator, which makes them expensive and not suitable for high-throughput screening. Recently, microfluidics has been used to automate many of the operations (e.g. sorting, positioning, drug delivery) associated with the Drosophila drug discovery assays and thereby increase their throughput. This review highlights recent microfluidic devices that have been developed for Drosophila assays with primary application towards drug discovery for human diseases. The microfluidic devices that have been reviewed in this paper are categorized based on the stage of the Drosophila that have been used. In each category, the microfluidic technologies behind each device are described and their potential biological applications are discussed. PMID- 27194359 TI - Effect of Thermal and Shear Stressors on the Physical Properties, Structural Integrity and Biological Activity of the Anti-TNF-alpha Monoclonal Antibody, Infliximab. AB - The influence of thermal and shear stressors on the stability of the anti-TNF alpha monoclonal antibody (mAb), Infliximab(r) (INF) was investigated. INF at concentrations of 1, 4 and 10 mg/ml was subjected to thermal stress at temperatures of 25-65 degrees C and to shear force by sonication for 1 and 3 minutes. The stressed samples were analysed for physical properties by particle size, zeta potential, for structural integrity by gel electrophoresis (SDS-PAGE) and circular dichroism, INF content by UV spectroscopy and for biological activity by ELISA. Results show no change in physical properties or structural integrity of INF at any concentration tested, when subjected to a temperature of up to 50 degrees C. At 65 degrees C, aggregation and precipitation of INF was observed. When subjected to shear stress, higher concentrations of INF at 4 and 10mg/ml maintained their physical properties and structural integrity. However, the biological activity of INF was found to decrease with increasing temperature and sonication time, and was concentration dependent (ANOVA; p<0.05). Interestingly, lyophilisation of INF at 1mg/ml did not affect its physical properties, structural integrity or its biological activity. These findings have important implications with respect to pharmaceutical processing of INF and mAbs including formulation as polymeric micro and nanoparticle systems for sustained or targeted delivery. These findings also have important implications with respect to the handling and storage of INF and mAbs for clinical use. PMID- 27194360 TI - Recent Developments of Three-Dimensional Paper-Based Electrochemical Devices for Cancer Cell Detection and Anticancer Drug Screening. AB - Cancer, as the most serious threat to human health, poses millions of deaths in the world each year. In vitro cancer cell and biomarker detection is of great importance for early cancer diagnosis and therapy, which needs highly sensitive, selective and quantitative diagnosis platforms. Threedimensional paper-based electrochemical devices (3D-PEDs) have attracted considerable interest in biomedical fields in recent years based on their simplicity, low cost, portability, high sensitivity and selectivity. Recently, since 3D-PEDs can particularly provide in vitro 3D structures to mimic the native 3D cell microenvironment, they have been used to detect cancer cells and monitor their responses to anticancer drug treatment in terms of cancer cell concentration, cancer cell apoptosis and cancer biomarkers. This review discusses the recent development of 3D-PEDs and their applications in detection of cancer cells and anticancer drug screening. PMID- 27194362 TI - Valuing therapeutic alliances with people experiencing acute psychosis. PMID- 27194361 TI - Empowering Translational Research in Fetal Growth Restriction: Sheep and Swine Animal Models. AB - Fetal or intrauterine growth restriction (FGR or IUGR) is a concerning health issue not only due to its implications in mortality and morbidity of neonates but also because of its long-term consequences on health and disease risk of the individuals. Its main cause is an insufficient supply of nutrients and oxygen by maternal (malnutrition or hypobaric hypoxia) or placental factors (placental insufficiency) during late gestation, when the requirements of fetus are higher. The availability of reliable animal models would be highly useful for the future development of diagnostic, preventive and therapeutic strategies. Most of the studies using animal models have been performed in rodents, while the use of large animals (sheep and swine) has been scarce. The objective of the current review is to offer an overview on the possibilities of using large animals for conducting translational research on IUGR related to inadequate maternal conditions and/or placental dysfunction. PMID- 27194363 TI - Molecular Investigation of the Mechanism of Non-Enzymatic Hydrolysis of Proteins and the Predictive Algorithm for Susceptibility. AB - A number of potential degradation routes can limit the shelf life of a biotherapeutic. While these are experimentally measurable, the tests to do so require a substantial investment in both time and material, resources rarely available early in the drug development process. To address the potential degradation route of non-enzymatic hydrolysis, we performed a molecular modeling analysis, together with an experimental study, to gain detailed insight into the reaction. On the basis of the mechanism, an algorithm for predicting the likely cleavage sites of a protein has been created. This algorithm measures four key properties during a molecular dynamics simulation, which relate to the key steps of the hydrolysis mechanism, in particular the rate-determining step (which can vary depending on the local environment). The first two properties include the secondary structure and the surface exposure of the amide bond, both of which help detect if the addition of the proton to the amide bond is possible. The second two properties relate to whether the side chain can cyclize and form a furane ring. These two properties are the orientation of the side chain relative to the amide bond and the number of hydrogen bonds between the side chain and the surrounding protein. Overall, the algorithm performs well at identifying reactive versus nonreactive bonds. The algorithm correctly classifies nearly 90% of all amide bonds following an aspartic or glutamic acid residue as reactive or nonreactive. PMID- 27194364 TI - Long-term outcomes of simultaneous guided bone regeneration using native and cross-linked collagen membranes after 8 years. AB - OBJECTIVES: To assess the clinical outcomes of simultaneous guided bone regeneration using native (CM) and cross-linked (VN) collagen membranes at 8 years. MATERIALS AND METHODS: A total of n = 19 patients (19 implants) were available for the analysis. Each subject had received a simultaneous grafting of dehiscence-type defects using a natural bone mineral (NBM) and a random allocation to either CM and VN membranes (submerged healing of 4 months). Clinical parameters (e.g., bleeding on probing - BOP, probing pocket depth - PD, mucosal recession - MR, clinical attachment level - CAL) were recorded at 8 years after prosthesis installation. RESULTS: At 8 years, CM and VN groups revealed comparable median BOP, PD, MR and CAL values at both vestibular and oral aspects. From 4 to 8 years (n = 14 patients), median CAL at the vestibular aspect improved in both groups; however, these changes were significantly higher at CM-treated sites (CM: 0.7 mm vs. VN: 0.5 mm). CONCLUSION: The clinical long-term outcomes at 8 years were comparable in both VN and CM groups. PMID- 27194365 TI - Wettability of PEDOT:PSS films. AB - Conducting polymers such as poly(3,4-ethylenedioxythiophene) polystyrene sulfonate ( PEDOT: PSS) are increasingly used to interface electronics with biology. Their wettability, however, remains poorly understood. We show that the frequently-used sessile drop technique yields results that are strongly dependent on the experimental conditions (measurement duration and relative humidity), due to the hydrogel-like behavior of PEDOT: PSS. In contrast, the captive bubble technique on a fully wet film overcomes these limitations. Dynamic wettability measurements provide hysteresis values for this polymer and clarify the physical meaning of the static contact angles measured by sessile drop and captive bubble. Finally we show that aging the films in water leads to loss of PSS chains which makes the films more hydrophobic. The addition of a crosslinker reduces and slows down these effects. PMID- 27194367 TI - Release of (14)C-labelled carbon nanotubes from polycarbonate composites. AB - Waste disposal of carbon nanotube (CNT) containing products is expected to be the most important pathway for release of CNTs into the environment. In the present work, the use of radiolabelled CNTs ((14)C-CNT) for polycarbonate polymer nanocomposites with 1 wt% (14)C-CNT content allowed for the first time to quantify and differentiate the CNT release according to the type of impact along the materials' ageing history. After an initial exposure of the nanocomposite by solar-like irradiation, further environmental impacts were applied to composite material. They aimed at mimicking disposal site conditions that may induce further ageing effects and CNT release. This study included shaking in water, rapid temperature changes, soaking in humic acid solution as well as waste water effluent, and, finally, gentle mechanical abrasion. All ageing impacts were applied sequentially, both on pristine (control) and on solar-irradiated nanocomposites. All experiments were accompanied by absolute quantification of radioactive release as well as chemical and morphological analyses of the nanocomposite surfaces using infra-red (IR) spectroscopy, X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). The morphological analysis showed that spectral irradiation can uncover CNT networks on the outer nanocomposite surface layers by polymer degradation. After having subjected the solar-irradiated nanocomposite to all studied disposal site effect, the total radioactive release was quantified to amount to 64 mg CNT/m(2), whereas only 0.8 mg CNT/m(2) were found for the un-irradiated control sample. Solar degradation of polymers was thus found to significantly increase the propensity of the studied polymer nanocomposites to release CNTs during ageing effects at the product's end of-life typical for disposal sites. PMID- 27194368 TI - Elevated levels of tissue plasminogen activator and E-selectin in male children with autism spectrum disorder. AB - Although the etiopathology of autism spectrum disorder (ASD) is not clear, immune dysfunction has been proposed as a mechanism for the pathophysiology of ASD. The purpose of this study is to examine serum levels of tissue plasminogen activator (t-PA) and some adhesion molecules in children with ASD that have not been investigated previously in detail. The study group included 35 male children aged from 2 to 9 diagnosed with ASD according to DSM-V criteria. Soluble platelet endothelial adhesion molecule-1 (sPECAM-1), P-selectin, E-selectin, and t-PA in the serum were determined with enzyme-linked immunosorbent assay. Autism behavior check list (ABC) is used for the assessment of ASD severity. The levels of t-PA (P = 0.025) and E-selectin (P = 0.007) was detected significantly higher in children with ASD than control group. Serum levels of sPECAM-1 showed statistically significant negative correlation with sensory, body and object-use, language, social, and self-help and total scores in the patient group (r = 0.349, P = 0.04; r = -0.411, P = 0.01; r = -0.412, P = 0.01; r = -0.417, P = 0.01, and r = -0.531, P < 0.01, respectively). Serum levels of P-selectin levels showed statistically significant negative correlation with ABC total score in the patient group (r = -0.378, P = 0.03). It may be suggested that t-PA, E-selectin, P-selectin, and sPECAM-1 a crucial role in inflammatory conditions in children with ASD. Autism Res 2016, 9: 1241-1247. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc. PMID- 27194366 TI - Physico-chemical properties and biological effects of diesel and biomass particles. AB - Diesel combustion and solid biomass burning are the major sources of ultrafine particles (UFP) in urbanized areas. Cardiovascular and pulmonary diseases, including lung cancer, are possible outcomes of combustion particles exposure, but differences in particles properties seem to influence their biological effects. Here the physico-chemical properties and biological effects of diesel and biomass particles, produced under controlled laboratory conditions, have been characterized. Diesel UFP were sampled from a Euro 4 light duty vehicle without DPF fuelled by commercial diesel and run over a chassis dyno. Biomass UFP were collected from a modern automatic 25 kW boiler propelled by prime quality spruce pellet. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) images of both diesel and biomass samples showed aggregates of soot particles, but in biomass samples ash particles were also present. Chemical characterization showed that metals and PAHs total content was higher in diesel samples compared to biomass ones. Human bronchial epithelial (HBEC3) cells were exposed to particles for up to 2 weeks. Changes in the expression of genes involved in xenobiotic metabolism were observed after exposure to both UFP already after 24 h. However, only diesel particles modulated the expression of genes involved in inflammation, oxidative stress and epithelial-to-mesenchymal transition (EMT), increased the release of inflammatory mediators and caused phenotypical alterations, mostly after two weeks of exposure. These results show that diesel UFP affected cellular processes involved in lung and cardiovascular diseases and cancer. Biomass particles exerted low biological activity compared to diesel UFP. This evidence emphasizes that the study of different emission sources contribution to ambient PM toxicity may have a fundamental role in the development of more effective strategies for air quality improvement. PMID- 27194370 TI - Doxazosin treatment of phaeochromocytoma during pregnancy: placental transfer and disposition in breast milk. PMID- 27194369 TI - A Serious Game for Massive Training and Assessment of French Soldiers Involved in Forward Combat Casualty Care (3D-SC1): Development and Deployment. AB - BACKGROUND: The French Military Health Service has standardized its military prehospital care policy in a ''Sauvetage au Combat'' (SC) program (Forward Combat Casualty Care). A major part of the SC training program relies on simulations, which are challenging and costly when dealing with more than 80,000 soldiers. In 2014, the French Military Health Service decided to develop and deploy 3D-SC1, a serious game (SG) intended to train and assess soldiers managing the early steps of SC. OBJECTIVES: The purpose of this paper is to describe the creation and production of 3D-SC1 and to present its deployment. METHODS: A group of 10 experts and the Paris Descartes University Medical Simulation Department spin off, Medusims, coproduced 3D-SC1. Medusims are virtual medical experiences using 3D real-time videogame technology (creation of an environment and avatars in different scenarios) designed for educational purposes (training and assessment) to simulate medical situations. These virtual situations have been created based on real cases and tested on mannequins by experts. Trainees are asked to manage specific situations according to best practices recommended by SC, and receive a score and a personalized feedback regarding their performance. RESULTS: The scenario simulated in the SG is an attack on a patrol of 3 soldiers with an improvised explosive device explosion as a result of which one soldier dies, one soldier is slightly stunned, and the third soldier experiences a leg amputation and other injuries. This scenario was first tested with mannequins in military simulation centers, before being transformed into a virtual 3D real-time scenario using a multi-support, multi-operating system platform, Unity. Processes of gamification and scoring were applied, with 2 levels of difficulty. A personalized debriefing was integrated at the end of the simulations. The design and production of the SG took 9 months. The deployment, performed in 3 months, has reached 84 of 96 (88%) French Army units, with a total of 818 hours of connection in the first 3 months. CONCLUSIONS: The development of 3D-SC1 involved a collaborative platform with interdisciplinary actors from the French Health Service, a university, and videogame industry. Training each French soldier with simulation exercises and mannequins is challenging and costly. Implementation of SGs into the training program could offer a unique opportunity at a lower cost to improve training and subsequently the real-time performance of soldiers when managing combat casualties; ideally, these should be combined with physical simulations. PMID- 27194371 TI - Oxygenation and neuromuscular activation of the quadriceps femoris including the vastus intermedius during a fatiguing contraction. AB - INTRODUCTION: The purpose of this study was to assess oxygenation and neuromuscular activation of the quadriceps femoris muscle group, including the vastus intermedius (VI), during a fatiguing contraction. METHODS: Eleven healthy men performed an isometric knee extension at 50% of the maximum voluntary contraction until failure. Near-infrared spectroscopy was used to measure tissue oxygen saturation (StO2 ), and surface electromyography was used to quantify the median frequency (MF) of the four individual quadriceps femoris muscles. RESULTS: A significant decrease in StO2 began at 25% of time to exhaustion in all four muscles, and StO2 of the VI was significantly higher than StO2 of the vastus medialis (VM) from 25% of time to exhaustion until 95% of time to exhaustion. The MF of the VI did not significantly decrease during the fatiguing task. We found a significant correlation between ?MF and ?StO2 in the VI (r = 0.745, P<0.01) and a significant correlation between StO2 and time to exhaustion in the VM and rectus femoris (RF) (VM, r = 0.684, P<0.05; RF, r = 0.635, P<0.05). CONCLUSION: These results suggest that muscle O2 saturation in the VI is associated with neuromuscular fatigue during a fatiguing isometric contraction, and the level of oxygenation in the VM and RF is a key to sustaining a fatiguing contraction. PMID- 27194372 TI - Favorable Effects of Oxygen Inhalation in Patients After Bidirectional Glenn Procedure as Assessed by Cardiovascular Magnetic Resonance Flow Measurement. AB - BACKGROUND: Home oxygen therapy (HOT) is used to adapt patients to the bidirectional Glenn (BDG) physiology. However, the precise cardiovascular effect of oxygen inhalation is still unknown. We used phase-contrast MRI to evaluate the cardiovascular effects of oxygen inhalation in young patients with BDG physiology. METHODS AND RESULTS: The 56 sessions of cardiac MRI were performed in 36 patients with BDG circulation. Oxygen saturation (SpO2) and heart rate (HR) were monitored under both room air and nasal 100% oxygen inhalation, and the blood flow volumes of the ascending aorta (AA), superior vena cava (SVC), and inferior vena cava (IVC) were measured by phase-contrast MRI. Systemic-to pulmonary collateral flow (SPCF) volumes were calculated by subtracting the sum of flow volumes through the SVC and IVC from the flow volume through the AA, and used for further comparative examination. Under nasal oxygen inhalation, SpO2significantly increased from 82% to 89%, while HR decreased from 115 to 110 beats/min. AA (5.0 vs. 4.9 L.min(-1).m(-2)), SVC (1.85 vs. 1.77 L.min(-1).m(-2)), and systemic blood flow volume (=SVC+IVC) significantly decreased (3.60 vs. 3.46 L.min(-1).m(-2)). In contrast, SPCF and the pulmonary-to-systemic blood flow ratio (Qp/Qs) remained unchanged. CONCLUSIONS: Oxygen inhalation improved arterial blood oxygenation and lowered HR in patients with BDG circulation without an increase in Qp/Qs. HOT would be protective of the cardiovascular system in patients with BDG circulation. (Circ J 2016; 80: 1378-1385). PMID- 27194374 TI - Current Treatment Strategy for Spontaneous Isolated Dissection of the Superior Mesenteric Artery. PMID- 27194373 TI - Raison d'etre of Tibial Artery Bypass for Intermittent Claudication in the Era of Endovascular Therapy. AB - BACKGROUND: There is currently no positive opinion regarding infrapopliteal revascularization for intermittent claudication (IC) in any guidelines. The aim of this study was to analyze the outcomes of infragenicular bypass and verify the adequacy of tibial artery bypass for IC. METHODS AND RESULTS: Over a 21-year period, 58 below-knee popliteal artery (BKPOP) bypasses and 35 tibial artery bypasses were performed for IC caused by arteriosclerosis obliterans. Graft patency and major amputation (MA) were examined as primary endpoints and the predictor of each outcome was estimated by multivariate analysis. The primary patency (PP), secondary patency (SP), and freedom from MA (ffMA) rates of a prosthetic/vein graft in all cases at 5 years were 19/68%, 22/86%, and 78/100% (P<0.01 in all). Limited to vein graft cases, PP and SP rates of popliteal/tibial bypass at 5 years were 73/62% (P=0.32) and 92/80% (P=0.22), respectively. In tibial artery bypass with a vein graft, the PP and SP rates of a single saphenous vein/spliced vein graft at 5 years were 71/46% (P=0.11) and 89/61% (P=0.03). A prosthetic graft was a common negative predictor for graft patency and MA by multivariate analysis. CONCLUSIONS: Tibial artery bypass is an acceptable treatment option for IC when a single saphenous vein can be harvested as a graft conduit. (Circ J 2016; 80: 1460-1469). PMID- 27194375 TI - Management of isolated cricopharyngeal dysfunction: systematic review. AB - OBJECTIVE: A systematic review was performed to evaluate the safety and efficacy of different therapeutic interventions available for the management of isolated cricopharyngeal dysfunction. METHODS: Studies were identified using the following databases: Ovid (Medline, Embase), the Cochrane Library, PubMed and Google Scholar. An initial search identified 339 articles. All titles and abstracts were reviewed. Fifty-six relevant articles were inspected in more detail; of these, 47 were included in the qualitative analysis. RESULTS: No relevant randomised trials were found. A range of case series were used to perform a qualitative analysis. Botulinum toxin A injection and cricopharyngeal dilatation were associated with a higher risk of recurrence, but appear to be more suitable in elderly and co morbid patients. In those patients requiring formal myotomy, endoscopic approaches appear to be as effective but less morbid when compared with classical open surgery. CONCLUSION: There is good evidence for the safety and efficacy of the different therapeutic options for isolated cricopharyngeal dysfunction. However, further studies are required to compare the efficacy of the various treatment modalities. PMID- 27194377 TI - China's Rural Cooperative Medical Scheme: a type of health insurance or a type of health cooperative? AB - The Cooperative Medical Scheme (CMS) was popular in rural China in the 1960s and 1970s, having garnered praise from the World Bank and World Health Organization as an unprecedented example of a successful health care model in a low-income developing country. However, the CMS almost collapsed in the 1980s. Based on its historical origins and main activities, we think the CMS functioned as a health cooperative rather than a health insurance scheme. Perhaps, however, the importance to the CMS of cooperation between institutions has been overestimated. Overlooked, yet equally important, has been the cooperation between health workers and farmers to target health-related risk factors associated with agricultural work and ways of life. The 'cooperative' character of the CMS includes two aspects: cooperative institutions and cooperative behaviour. Although the CMS collapsed in China, similar schemes are flourishing elsewhere in the world. In the future, in-depth analysis of these schemes is required. PMID- 27194376 TI - Mechanistic insight into cadmium-induced inactivation of the Bloom protein. AB - Cadmium is a toxic metal that inactivates DNA-repair proteins via multiple mechanisms, including zinc substitution. In this study, we investigated the effect of Cd(2+) on the Bloom protein (BLM), a DNA-repair helicase carrying a zinc-binding domain (ZBD) and playing a critical role to ensure genomic stability. One characteristics of BLM-deficient cells is the elevated rate of sister chromatid exchanges, a phenomenon that is also induced by Cd(2+). Here, we show that Cd(2+) strongly inhibits both ATPase and helicase activities of BLM. Cd(2+) primarily prevents BLM-DNA interaction via its binding to sulfhydryl groups of solvent-exposed cysteine residues and, concomitantly, promotes the formation of large BLM multimers/aggregates. In contrast to previously described Cd(2+) effects on other zinc-containing DNA-repair proteins, the ZBD appears to play a minor role in the Cd(2+)-mediated inhibition. While the Cd(2+)-dependent formation of inactive multimers and the defect of DNA-binding were fully reversible upon addition of EDTA, the inhibition of the DNA unwinding activity was not counteracted by EDTA, indicating another mechanism of inhibition by Cd(2+) relative to the targeting of a catalytic residue. Altogether, our results provide new clues for understanding the mechanism behind the ZBD-independent inactivation of BLM by Cd(2+) leading to accumulation of DNA double-strand breaks. PMID- 27194379 TI - Methodological considerations of electron spin resonance spin trapping techniques for measuring reactive oxygen species generated from metal oxide nanomaterials. AB - Qualitative and quantitative analyses of reactive oxygen species (ROS) generated on the surfaces of nanomaterials are important for understanding their toxicity and toxic mechanisms, which are in turn beneficial for manufacturing more biocompatible nanomaterials in many industrial fields. Electron spin resonance (ESR) is a useful tool for detecting ROS formation. However, using this technique without first considering the physicochemical properties of nanomaterials and proper conditions of the spin trapping agent (such as incubation time) may lead to misinterpretation of the resulting data. In this report, we suggest methodological considerations for ESR as pertains to magnetism, sample preparation and proper incubation time with spin trapping agents. Based on our results, each spin trapping agent should be given the proper incubation time. For nanomaterials having magnetic properties, it is useful to remove these nanomaterials via centrifugation after reacting with spin trapping agents. Sonication for the purpose of sample dispersion and sample light exposure should be controlled during ESR in order to enhance the obtained ROS signal. This report will allow researchers to better design ESR spin trapping applications involving nanomaterials. PMID- 27194380 TI - Valley-Coherent Hot Carriers and Thermal Relaxation in Monolayer Transition Metal Dichalcogenides. AB - We show room-temperature valley coherence in MoS2, MoSe2, WS2, and WSe2 monolayers using linear polarization-resolved hot photoluminescence (PL) at energies close to the excitation, demonstrating preservation of valley coherence before sufficient scattering events. The features of the copolarized hot luminescence allow us to extract the lower bound of the binding energy of the A exciton in monolayer MoS2 as 0.42 (+/-0.02) eV. The broadening of the PL peak is found to be dominated by a Boltzmann-type hot luminescence tail, and using the slope of the exponential decay, the carrier temperature is extracted in situ at different stages of energy relaxation. The temperature of the emitted optical phonons during the relaxation process is probed by exploiting the corresponding broadening of the Raman peaks due to temperature-induced anharmonic effects. The findings provide a physical picture of photogeneration of valley-coherent hot carriers and their subsequent energy relaxation pathways. PMID- 27194378 TI - A Preliminary Study of DBH (Encoding Dopamine Beta-Hydroxylase) Genetic Variation and Neural Correlates of Emotional and Motivational Processing in Individuals With and Without Pathological Gambling. AB - Background and aims Corticostriatal-limbic neurocircuitry, emotional and motivational processing, dopaminergic and noradrenergic systems and genetic factors have all been implicated in pathological gambling (PG). However, allelic variants of genes influencing dopaminergic and noradrenergic neurotransmitters have not been investigated with respect to the neural correlates of emotional and motivational states in PG. Dopamine beta-hydroxylase (DBH) converts dopamine to norepinephrine; the T allele of a functional single-nucleotide polymorphism rs1611115 (C-1021T) in the DBH gene is associated with less DBH activity and has been linked to emotional processes and addiction. Here, we investigate the influence of rs1611115 on the neural correlates of emotional and motivational processing in PG and healthy comparison (HC) participants. Methods While undergoing functional magnetic resonance imaging, 18 PG and 25 HC participants, all European Americans, viewed gambling-, sad-, and cocaine-related videotapes. Analyses focused on brain activation differences related to DBH genotype (CC/T carrier [i.e., CT and TT]) and condition (sad/gambling/cocaine). Results CC participants demonstrated greater recruitment of corticostriatal-limbic regions, relative to T-carriers. DBH variants were also associated with altered corticostriatal-limbic activations across the different videotape conditions, and this association appeared to be driven by greater activation in CC participants relative to T-carriers during the sad condition. CC relative to T-carrier subjects also reported greater subjective sadness to the sad videotapes. Conclusions Individual differences in genetic composition linked to aminergic function contribute significantly to emotional regulation across diagnostic groups and warrant further investigation in PG. PMID- 27194381 TI - Efficacy of Fluidized Bed Bioartificial Liver in Treating Fulminant Hepatic Failure in Pigs: A Metabolomics Study. AB - Bioartificial livers may act as a promising therapy for fulminant hepatic failure (FHF) with better accessibility and less injury compared to orthotopic liver transplantation. This study aims to evaluate the efficacy and safety of a fluidized bed bioartificial liver (FBBAL) and to explore its therapeutic mechanisms based on metabolomics. FHF was induced by D-galactosamine. Eighteen hours later, pigs were treated with an FBBAL containing encapsulated primary porcine hepatocytes (B group), with a sham FBBAL (containing cell-free capsules, S group) or with only intensive care (C group) for 6 h. Serum samples were assayed using ultra-performance liquid chromatography-mass spectrometry. The difference in survival time (51.6 +/- 7.9 h vs. 49.3 +/- 6.6 h) and serum metabolome was negligible between the S and C groups, whereas FBBAL treatment significantly prolonged survival time (70.4 +/- 11.5h, P < 0.01) and perturbed the serum metabolome, resulting in a marked decrease in phosphatidylcholines, lysophosphatidylcholines, sphingomyelinase, and fatty acids and an increase in conjugated bile acids. The FBBAL exhibits some liver functions and may exert its therapeutic effect by altering the serum metabolome of FHF pigs. Moreover, alginate-chitosan capsules have less influence on serum metabolites. Nevertheless, the alterations were not universally beneficial, revealing that much should be done to improve the FBBAL. PMID- 27194382 TI - A common medication for neuropsychiatric illnesses may cause common problems in pregnancy. PMID- 27194383 TI - Prehospital systolic blood pressure is higher in acute stroke compared with stroke mimics. AB - OBJECTIVE: To assess the natural history of prehospital blood pressure (BP) during emergency medical services (EMS) transport of suspected stroke and determine whether prehospital BP differs among types of patients with suspected stroke (ischemic stroke, TIA, intracerebral hemorrhage [ICH], or stroke mimic). METHODS: A retrospective, cross-sectional, observational analysis of a centralized EMS database containing electronic records of patients transported by EMS to the emergency department (ED) with suspected stroke during an 18-month period was conducted. Hospital charts and neuroimaging were utilized to determine the final diagnosis (ischemic stroke, TIA, ICH, or stroke mimic). RESULTS: A total of 960 patients were transported by EMS to ED with suspected stroke. Stroke was diagnosed in 544 patients (56.7%) (38.2% ischemic stroke, 12.2% TIA, 5.3% ICH) and 416 (43.2%) were considered mimics. Age-adjusted mean prehospital systolic BP (SBP) was higher in acute stroke patients (155.6 mm Hg; 95% confidence interval [CI]: 153.4-157.9 mm Hg) compared to mimics (146.1 mm Hg; 95% CI: 142.5-148.6 mm Hg; p < 0.001). Age-adjusted mean prehospital SBP was higher in ICH (172.3 mm Hg; 95% CI: 165.1-179.7 mm Hg) than in either ischemic stroke or TIA (154.7 mm Hg; 95% CI: 152.3-157.0 mm Hg; p < 0.001). Median (interquartile range) SBP drop from initial prehospital SBP to ED SBP was 4 mm Hg (-6 to 17 mm Hg). Mean prehospital SBP was strongly correlated with ED SBP (r = 0.82, p < 0.001). CONCLUSIONS: Prehospital SBP is higher in acute stroke relative to stroke mimics and highest in ICH. Given the stability of BP between initial EMS and ED measurements, it may be reasonable to test the feasibility and safety of prehospital antihypertensive therapy in patients with suspected acute stroke. PMID- 27194384 TI - Presymptomatic ALS genetic counseling and testing: Experience and recommendations. AB - Remarkable advances in our understanding of the genetic contributions to amyotrophic lateral sclerosis (ALS) have sparked discussion and debate about whether clinical genetic testing should routinely be offered to patients with ALS. A related, but distinct, question is whether presymptomatic genetic testing should be offered to family members who may be at risk for developing ALS. Existing guidelines for presymptomatic counseling and testing are mostly based on small number of individuals, clinical judgment, and experience from other neurodegenerative disorders. Over the course of the last 8 years, we have provided testing and 317 genetic counseling sessions (including predecision, pretest, posttest, and ad hoc counseling) to 161 first-degree family members participating in the Pre-Symptomatic Familial ALS Study (Pre-fALS), as well as testing and 75 posttest counseling sessions to 63 individuals with familial ALS. Based on this experience, and the real-world challenges we have had to overcome in the process, we recommend an updated set of guidelines for providing presymptomatic genetic counseling and testing to people at high genetic risk for developing ALS. These recommendations are especially timely and relevant given the growing interest in studying presymptomatic ALS. PMID- 27194385 TI - Pregnancy outcome following maternal exposure to pregabalin may call for concern. AB - OBJECTIVE: To investigate pregnancy outcomes following maternal use of pregabalin. METHODS: This multicenter, observational prospective cohort study compared pregnancy outcomes in women exposed to pregabalin with those of matched controls (not exposed to any medications known to be teratogenic or to any antiepileptic drugs). Teratology Information Services systematically collected data between 2004 and 2013. RESULTS: Data were collected from 164 exposed pregnancies and 656 controls. A significantly higher major birth defect rate in the pregabalin group was observed after exclusion of chromosomal aberration syndromes, and when cases with exposure during first trimester of pregnancy were analyzed separately (7/116 [6.0%] vs 12/580 [2.1%]; odds ratio 3.0, 95% confidence interval 1.2-7.9, p = 0.03). The rate of live births was lower in the pregabalin group (71.9% vs 85.2%, p < 0.001), primarily due to a higher rate of both elective (9.8% vs 5.0%, p = 0.02) and medically indicated (5.5% vs 1.8%, p = 0.008) pregnancy terminations. In the Cox proportional cause specific hazards model, pregabalin exposure was not associated with a significantly higher risk of spontaneous abortion. CONCLUSIONS: This study demonstrated a signal for increased risk of major birth defects after first trimester exposure to pregabalin. However, several limitations such as the small sample size, differences across groups in maternal conditions, and concomitant medication exposure exclude definitive conclusions, so these results call for confirmation through independent studies. PMID- 27194386 TI - Investigating the role of cortisol and growth hormone in fatty liver development: fatty liver index in patients with pituitary adenomas. AB - PURPOSE: Non-alcoholic fatty liver disease (NAFLD) is a hallmark of the metabolic syndrome and has been shown to be an independent predictor of cardiovascular mortality. Although glucocorticoids and growth hormone are known to be implicated in its pathophysiology, it has only rarely been investigated in the context of patients with pituitary insufficiency or former cortisol excess. METHODS: Case control study in patients with biochemically controlled Cushing's disease (CD; N = 33) and non-functioning pituitary adenomas (NFPA; N = 79). NAFLD was estimated by calculating the fatty liver index (FLI) including BMI, waist circumference, GGT and triglyceride levels. RESULTS: Although there was no difference in FLI between patients with NFPA and CD, we identified average daily hydrocortisone (HC) intake in those with adrenal insufficiency to be an independent predictor of FLI (beta = 1.124; p = 0.017), even after adjusting for BMI and waist circumference. In line, those with a FLI > 60 were also taking in average significantly more HC per day than those with a score <60 (21.05 mg +/- 5.9 vs. 17.9 mg +/- 4.4; p = 0.01). FLI was also the best independent predictor for HbA1c and fasting glucose levels (both p = 0.001). Growth hormone deficiency and replacement therapy were not associated with FLI in either group. CONCLUSIONS: While HC dosage affects FLI as an estimate of NFLD in patients with CD and NFPA, the benefit of GH replacement still needs to be determined. In contrast to reports in CD patients with active disease, NAFLD in those with biochemical control was not different from NFPA patients. PMID- 27194387 TI - Structural basis of omalizumab therapy and omalizumab-mediated IgE exchange. AB - Omalizumab is a widely used therapeutic anti-IgE antibody. Here we report the crystal structure of the omalizumab-Fab in complex with an IgE-Fc fragment. This structure reveals the mechanism of omalizumab-mediated inhibition of IgE interactions with both high- and low-affinity IgE receptors, and explains why omalizumab selectively binds free IgE. The structure of the complex also provides mechanistic insight into a class of disruptive IgE inhibitors that accelerate the dissociation of the high-affinity IgE receptor from IgE. We use this structural data to generate a mutant IgE-Fc fragment that is resistant to omalizumab binding. Treatment with this omalizumab-resistant IgE-Fc fragment, in combination with omalizumab, promotes the exchange of cell-bound full-length IgE with omalizumab-resistant IgE-Fc fragments on human basophils. This combination treatment also blocks basophil activation more efficiently than either agent alone, providing a novel approach to probe regulatory mechanisms underlying IgE hypersensitivity with implications for therapeutic interventions. PMID- 27194390 TI - Primary hyperparathyroidism. PMID- 27194388 TI - Targeting human respiratory syncytial virus transcription anti-termination factor M2-1 to inhibit in vivo viral replication. AB - Human respiratory syncytial virus (hRSV) is a leading cause of acute lower respiratory tract infection in infants, elderly and immunocompromised individuals. To date, no specific antiviral drug is available to treat or prevent this disease. Here, we report that the Smoothened receptor (Smo) antagonist cyclopamine acts as a potent and selective inhibitor of in vitro and in vivo hRSV replication. Cyclopamine inhibits hRSV through a novel, Smo-independent mechanism. It specifically impairs the function of the hRSV RNA-dependent RNA polymerase complex notably by reducing expression levels of the viral anti termination factor M2-1. The relevance of these findings is corroborated by the demonstration that a single R151K mutation in M2-1 is sufficient to confer virus resistance to cyclopamine in vitro and that cyclopamine is able to reduce virus titers in a mouse model of hRSV infection. The results of our study open a novel avenue for the development of future therapies against hRSV infection. PMID- 27194391 TI - Zinc- and copper-porphyrins in aqueous solution - two similar complexes with strongly contrasting hydration. AB - We present detailed analysis of the hydration behavior of zinc and copper bound porphyrins treated via ab initio quantum mechanical charge field molecular dynamics which agrees well with available experimental data. The computed metal water coordination in the case of zinc bound porphyrin demonstrates a strong association of water with zinc compared to the copper-water interaction which correlates well with the calculated free energy of binding. The H-bond dynamics in these hydrated systems yield weaker H-bond interactions as compared to that observed in the case of metal-free porphyrin; nevertheless, the effect of metal association with porphyrin resulted in shifts in the vibrational frequencies. These characteristic data suggest a contrasting behavior between these metalloporphyrins in solution which could also serve to correlate with the properties of biological systems. PMID- 27194389 TI - Irc3 is a mitochondrial DNA branch migration enzyme. AB - Integrity of mitochondrial DNA (mtDNA) is essential for cellular energy metabolism. In the budding yeast Saccharomyces cerevisiae, a large number of nuclear genes influence the stability of mitochondrial genome; however, most corresponding gene products act indirectly and the actual molecular mechanisms of mtDNA inheritance remain poorly characterized. Recently, we found that a Superfamily II helicase Irc3 is required for the maintenance of mitochondrial genome integrity. Here we show that Irc3 is a mitochondrial DNA branch migration enzyme. Irc3 modulates mtDNA metabolic intermediates by preferential binding and unwinding Holliday junctions and replication fork structures. Furthermore, we demonstrate that the loss of Irc3 can be complemented with mitochondrially targeted RecG of Escherichia coli. We suggest that Irc3 could support the stability of mtDNA by stimulating fork regression and branch migration or by inhibiting the formation of irregular branched molecules. PMID- 27194392 TI - Force generation and wing deformation characteristics of a flapping-wing micro air vehicle 'DelFly II' in hovering flight. AB - The study investigates the aerodynamic performance and the relation between wing deformation and unsteady force generation of a flapping-wing micro air vehicle in hovering flight configuration. Different experiments were performed where fluid forces were acquired with a force sensor, while the three-dimensional wing deformation was measured with a stereo-vision system. In these measurements, time resolved power consumption and flapping-wing kinematics were also obtained under both in-air and in-vacuum conditions. Comparison of the results for different flapping frequencies reveals different wing kinematics and deformation characteristics. The high flapping frequency case produces higher forces throughout the complete flapping cycle. Moreover, a phase difference occurs in the variation of the forces, such that the low flapping frequency case precedes the high frequency case. A similar phase lag is observed in the temporal evolution of the wing deformation characteristics, suggesting that there is a direct link between the two phenomena. A considerable camber formation occurs during stroke reversals, which is mainly determined by the stiffener orientation. The wing with the thinner surface membrane displays very similar characteristics to the baseline wing, which implies the dominance of the stiffeners in terms of providing rigidity to the wing. Wing span has a significant effect on the aerodynamic efficiency such that increasing the span length by 4 cm results in a 6% enhancement in the cycle-averaged X-force to power consumption ratio compared to the standard DelFly II wings with a span length of 28 cm. PMID- 27194393 TI - A randomized controlled trial of self-regulated modified constraint-induced movement therapy in sub-acute stroke patients. AB - BACKGROUND AND PURPOSE: Emerging research suggests the use of self-regulation (SR) for improving functional regain in patients post stroke. SR is proposed to produce an added effect to effective modified constraint-induced movement therapy (mCIMT). This study aimed to examine the effect of a self-regulated mCIMT programme (SR-mCIMT) for functional regain in patients with sub-acute stroke. METHODS: Eighty-six patients completed the trial: SR-mCIMT, n = 29; mCIMT, n = 31; or conventional functional rehabilitation, n = 26. All interventions were 2 week therapist-guided training. Outcome measurements, taken by a blinded assessor, examined arm function [Action Research Arm Test (ARAT), Fugl-Meyer Assessment (FMA)], daily task performance [Lawton Instrumental Activities of Daily Living Scale (Lawton IADL)] and self-perceived arm use in functional tasks [Motor Activity Log (MAL)]. RESULTS: Significant differences were found with the SR-mCIMT outperforming the other groups after the intervention (ARAT, P = 0.006; FMA, Lawton IADL and MAL, all Ps < 0.001). In terms of the carry-over effect, the SR-mCIMT group outperformed in the hand and coordination subscales of ARAT and FMA (P = 0.012-0.013) and the self-perceived quality of arm use (P = 0.002). CONCLUSION: A combination of SR and mCIMT could produce an added effect in functional regain in patients post stroke. PMID- 27194396 TI - Preface. PMID- 27194395 TI - A Thioether-Stabilized d-Proline-l-Proline-Induced beta-Hairpin Peptide of Defensin Segment Increases Its Anti-Candida albicans Ability. AB - We report a beta-hairpin dual stabilizing strategy: a d-proline-l-proline (d-Pro l-Pro) dipeptide as the nucleating turn, and a thioether tether as a side-chain linkage at a precisely designed position to stabilize the beta-hairpin. This method was used to modify the C-terminal beta-hairpin moiety of the plant defensin, pv-defensin, in order to obtain a stabilized peptide with enhanced anti Candida albicans activity (MIC 84-3.0 MUm), high serum stability (50 % remaining after 48 h) and low hemolysis (<10 % at 152 MUm). This modified peptide penetrated the C. albicans cell membrane within 5 min and showed high activity against clinically isolated antibiotic-resistant C. albicans and Candida glabrata strains. PMID- 27194394 TI - Risk of extracolonic cancers for people with biallelic and monoallelic mutations in MUTYH. AB - Germline mutations in the DNA base excision repair gene MUTYH are known to increase a carrier's risk of colorectal cancer. However, the risks of other (extracolonic) cancers for MUTYH mutation carriers are not well defined. We identified 266 probands (91% Caucasians) with a MUTYH mutation (41 biallelic and 225 monoallelic) from the Colon Cancer Family Registry. Mutation status, sex, age and histories of cancer from their 1,903 first- and 3,255 second-degree relatives were analyzed using modified segregation analysis conditioned on the ascertainment criteria. Compared with incidences for the general population, hazard ratios (HRs) (95% confidence intervals [CIs]) for biallelic MUTYH mutation carriers were: urinary bladder cancer 19 (3.7-97) and ovarian cancer 17 (2.4 115). The HRs (95% CI) for monoallelic MUTYH mutation carriers were: gastric cancer 9.3 (6.7-13); hepatobiliary cancer 4.5 (2.7-7.5); endometrial cancer 2.1 (1.1-3.9) and breast cancer 1.4 (1.0-2.0). There was no evidence for an increased risk of cancers at the other sites examined (brain, pancreas, kidney or prostate). Based on the USA population incidences, the estimated cumulative risks (95% CI) to age 70 years for biallelic mutation carriers were: bladder cancer 25% (5-77%) for males and 8% (2-33%) for females and ovarian cancer 14% (2-65%). The cumulative risks (95% CI) for monoallelic mutation carriers were: gastric cancer 5% (4-7%) for males and 2.3% (1.7-3.3%) for females; hepatobiliary cancer 3% (2 5%) for males and 1.4% (0.8-2.3%) for females; endometrial cancer 3% (2%-6%) and breast cancer 11% (8-16%). These unbiased estimates of both relative and absolute risks of extracolonic cancers for people, mostly Caucasians, with MUTYH mutations will be important for their clinical management. PMID- 27194397 TI - The pharmacokinetics of dronedarone in normolipidemic and hyperlipidemic rats. AB - The objectives of the current study were to characterize the pharmacokinetic profile of dronedarone in the rat, and to examine the effect of hyperlipidemia on its pharmacokinetics. Single doses of dronedarone were administered to rats intravenously (4 mg/kg), orally (55 mg/kg) and intraperitoneally (65 mg/kg). To induce hyperlipidemia, some of the rats were administered intraperitoneal doses of poloxamer 407 before giving an oral dose of dronedarone. After intravenous doses of 4 mg/kg dronedarone, plasma clearance and volume of distribution at steady-state were 25.1 +/- 8.09 mL/min/kg and 10.8 +/- 4.77 L/kg, respectively. After oral doses the maximum plasma concentrations (Cmax) and their median time of attainment (tmax) were 1.87 +/- 1.65 mg/mL and 3.5 h, respectively. Intraperitoneal administration of 65 mg/kg dronedarone base yielded plasma Cmax and median tmax of 0.816 +/- 0.611 mg/mL and 3 h, respectively. Protein binding was high in NL and HL plasma. Dronedarone is extensively distributed with high volume of distribution in the rat. The drug showed poor bioavailability (<20%) after oral and intraperitoneal administration. The increased plasma concentrations after oral dosing to hyperlipidemic rats appears to be attributable to a direct effect on metabolizing enzymes or transport proteins. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27194398 TI - Reduction of Tubulin Expression in Angomonas deanei by RNAi Modifies the Ultrastructure of the Trypanosomatid Protozoan and Impairs Division of Its Endosymbiotic Bacterium. AB - In the last two decades, RNA interference pathways have been employed as a useful tool for reverse genetics in trypanosomatids. Angomonas deanei is a nonpathogenic trypanosomatid that maintains an obligatory endosymbiosis with a bacterium related to the Alcaligenaceae family. Studies of this symbiosis can help us to understand the origin of eukaryotic organelles. The recent elucidation of both the A. deanei and the bacterium symbiont genomes revealed that the host protozoan codes for the enzymes necessary for RNAi activity in trypanosomatids. Here, we tested the functionality of the RNAi machinery by transfecting cells with dsRNA to a reporter gene (green fluorescent protein), which had been previously expressed in the parasite and to alpha-tubulin, an endogenous gene. In both cases, protein expression was reduced by the presence of specific dsRNA, inducing, respectively, a decreased GFP fluorescence and the formation of enlarged cells with modified arrangement of subpellicular microtubules. Furthermore, symbiont division was impaired. These results indicate that the RNAi system is active in A. deanei and can be used to further explore gene function in symbiont-containing trypanosomatids and to clarify important aspects of symbiosis and cell evolution. PMID- 27194400 TI - Fecal microbiota transplantation for the intestinal decolonization of extensively antimicrobial-resistant opportunistic pathogens: a review. AB - Treatment options for multidrug-resistant (MDR) bacterial infections are limited and often less effective. Non-pharmacologic approaches to preventing or treating MDR infections are currently restricted to improved antimicrobial stewardship and infection control practices. Fecal microbiota transplantation (FMT), a highly effective treatment for recurrent Clostridium difficile infection, has emerged as a promising therapy for intestinal MDR bacterial decolonization. A total of eight case reports have been published showing FMT resulted in intestinal decolonization of extended spectrum beta-lactamase (ESBL)-producing and carbapenemase-producing Enterobacteriaceae, vancomycin-resistant Enterococci, or methicillin-resistant Staphylococcus aureus. The procedure has been shown to work even in immunocompromised patients and those experiencing medical crises without any adverse events. Five trials are currently underway to further investigate the use of FMT for MDR bacterial decolonization. FMT is a completely novel way to eradicate drug-resistant bacteria from the intestinal reservoir and should be further investigated to address the global problem of difficult-to-treat, MDR bacterial infections. PMID- 27194401 TI - Estimation of lumbar spinal loading and trunk muscle forces during asymmetric lifting tasks: application of whole-body musculoskeletal modelling in OpenSim. AB - Large spinal compressive force combined with axial torsional shear force during asymmetric lifting tasks is highly associated with lower back injury (LBI). The aim of this study was to estimate lumbar spinal loading and muscle forces during symmetric lifting (SL) and asymmetric lifting (AL) tasks using a whole-body musculoskeletal modelling approach. Thirteen healthy males lifted loads of 7 and 12 kg under two lifting conditions (SL and AL). Kinematic data and ground reaction force data were collected and then processed by a whole-body musculoskeletal model. The results show AL produced a significantly higher peak lateral shear force as well as greater peak force of psoas major, quadratus lumborum, multifidus, iliocostalis lumborum pars lumborum, longissimus thoracis pars lumborum and external oblique than SL. The greater lateral shear forces combined with higher muscle force and asymmetrical muscle contractions may have the biomechanical mechanism responsible for the increased risk of LBI during AL. Practitioner Summary: Estimating lumbar spinal loading and muscle forces during free-dynamic asymmetric lifting tasks with a whole-body musculoskeletal modelling in OpenSim is the core value of this research. The results show that certain muscle groups are fundamentally responsible for asymmetric movement, thereby producing high lumbar spinal loading and muscle forces, which may increase risks of LBI during asymmetric lifting tasks. PMID- 27194399 TI - Cre-dependent DREADD (Designer Receptors Exclusively Activated by Designer Drugs) mice. AB - DREADDs, designer receptors exclusively activated by designer drugs, are engineered G protein-coupled receptors (GPCR) which can precisely control GPCR signaling pathways (for example, Gq, Gs, and Gi). This chemogenetic technology for control of GPCR signaling has been successfully applied in a variety of in vivo studies, including in mice, to remotely control GPCR signaling, for example, in neurons, glia cells, pancreatic beta-cells, or cancer cells. In order to fully explore the in vivo applications of the DREADD technology, we generated hM3Dq and hM4Di strains of mice which allow for Cre recombinase-mediated restricted expression of these pathway-selective DREADDs. With the many Cre driver lines now available, these DREADD lines will be applicable to studying a wide array of research and preclinical questions. genesis 54:439-446, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27194402 TI - Chordoid Glioma of Third Ventricle With an Epidermoid Cyst: Coexistence or Common Histogenesis? AB - Chordoid glioma (CG) is a World Health Organization classified grade II tumor located exclusively in the region of anterior third ventricle. Association of CG with other lesions is extremely rare. We report a case of CG in a 45-year-old male coexisting with an epidermoid cyst in the third ventricle. Ultrastructural examination of the CG revealed microvilli, junctional complexes, and intermediate filaments within the cytoplasm suggesting origin from specialized ependyma. The association of the 2 lesions appears coincidental as convincing evidence for a common histogenesis was not found. PMID- 27194403 TI - A randomized-controlled trial of high- or low-volume intravenous Plasma-Lyte((r)) to prevent hypotension during sedation for colonoscopy. AB - PURPOSE: The purpose of this study was to compare the incidence of hypotension during sedation in adults presenting for elective colonoscopy and randomized to intravenous Plasma-Lyte 148((r)) at either 2 mL.kg(-1) (low volume) or 20 mL.kg( 1) (high volume). METHODS: Patients aged >= 18 yr presenting for elective colonoscopy, with or without gastroscopy, after oral bowel preparation were randomized to receive the intervention immediately before the start of the procedure. Hypotension was defined as a >= 25% decrease in systolic blood pressure (SBP) from baseline during the procedure. Secondary outcomes included SBP < 90 mmHg, lowest SBP during sedation, duration of hypotension, use of vasopressors, postoperative outcomes, and cost. RESULTS: Seventy-five patients were randomly allocated to either the low-volume or high-volume group, respectively (total n = 150). The incidence of hypotension was similar in the two groups (59% vs 56%, respectively; odds ratio, 0.90; 95% confidence interval, 0.47 to 1.71; P = 0.74). The incidence of SBP < 90 mmHg, the lowest SBP during sedation, the duration of hypotension, the use of vasopressors, and postoperative outcomes were also similar in the two groups. CONCLUSIONS: This study does not support the routine use of 20 mL.kg(-1) of intravenous Plasma-Lyte 148 to prevent hypotension and other complications during sedation for elective colonoscopy in adult patients. Clinical Trials Registry (ANZCTR 12615001288516). PMID- 27194404 TI - Circumcision of male infants and children as a public health measure in developed countries: A critical assessment of recent evidence. AB - In December of 2014, an anonymous working group under the United States' Centers for Disease Control and Prevention (CDC) issued a draft of the first-ever federal recommendations regarding male circumcision. In accordance with the American Academy of Pediatrics' circumcision policy from 2012 - but in contrast to the more recent 2015 policy from the Canadian Paediatric Society as well as prior policies (still in force) from medical associations in Europe and Australasia - the CDC suggested that the benefits of the surgery outweigh the risks. In this article, we provide a brief scientific and conceptual analysis of the CDC's assessment of benefit versus risk, and argue that it deserves a closer look. Although we set aside the burgeoning bioethical debate surrounding the moral permissibility of performing non-therapeutic circumcisions on healthy minors, we argue that, from a scientific and medical perspective, current evidence suggests that such circumcision is not an appropriate public health measure for developed countries such as the United States. PMID- 27194405 TI - Fructose, but not glucose, impairs insulin signaling in the three major insulin sensitive tissues. AB - Human studies support the relationship between high intake of fructose-sweetened beverages and type 2 diabetes, but there is a debate on whether this effect is fructose-specific or it is merely associated to an excessive caloric intake. Here we investigate the effects of 2 months' supplementation to female rats of equicaloric 10% w/v fructose or glucose solutions on insulin sensitivity in target tissues. Fructose supplementation caused hepatic deposition of triglycerides and changed the fatty acid profile of this fraction, with an increase in monounsaturated and a decrease in polyunsaturated species, but did not cause inflammation and oxidative stress. Fructose but not glucose supplemented rats displayed an abnormal glucose tolerance test, and did not show increased phosphorylation of V-akt murine thymoma viral oncogene homolog-2 (Akt) in white adipose tissue and liver after insulin administration. In skeletal muscle, phosphorylation of Akt and of Akt substrate of 160 kDA (AS160) was not impaired but the expression of the glucose transporter type 4 (GLUT4) in the plasma membrane was reduced only in fructose-fed rats. In conclusion, fructose but not glucose supplementation causes fatty liver without inflammation and oxidative stress and impairs insulin signaling in the three major insulin responsive tissues independently from the increase in energy intake. PMID- 27194406 TI - Transfer of Two-Dimensional Oligonucleotide Patterns onto Stereocontrolled Plasmonic Nanostructures through DNA-Origami-Based Nanoimprinting Lithography. AB - The precise functionalization of self-assembled nanostructures with spatial and stereocontrol is a major objective of nanotechnology and holds great promise for many applications. Herein, the nanoscale addressability of DNA origami was exploited to develop a precise copy-machine-like platform that can transfer two dimensional oligonucleotide patterns onto the surface of gold nanoparticles (AuNPs) through a deliberately designed toehold-initiated DNA displacement reaction. This strategy of DNA-origami-based nanoimprinting lithography (DONIL) demonstrates high precision in controlling the valence and valence angles of AuNPs. These DNA-decorated AuNPs act as precursors in the construction of discrete AuNP clusters with desired chirality. PMID- 27194407 TI - Microbial translocation and skeletal muscle in young and old vervet monkeys. AB - Intestinal barrier dysfunction leads to microbial translocation (MT) and inflammation in vertebrate and invertebrate animal models. Age is recently recognized as a factor leading to MT, and in some human and animal model studies, MT was associated with physical function. We evaluated sarcopenia, inflammation, MT biomarkers, and muscle insulin sensitivity in healthy female vervet monkeys (6 27 years old). Monkeys were fed consistent diets and had large and varied environments to facilitate physical activity, and stable social conditions. Aging led to sarcopenia as indicated by reduced walking speeds and muscle mass, but general metabolic health was similar in older monkeys (n = 25) as compared to younger ones (n = 26). When older monkeys were physically active, their MT burden approximated that in young monkeys; however, when older monkeys were sedentary, MT burden was dramatically increased. MT levels were positively associated with inflammatory burden and negatively associated with skeletal muscle insulin sensitivity. Time spent being active was positively associated with insulin sensitivity as expected, but this relationship was specifically modified by the individual monkey's MT, not inflammatory burden. Our data supports clinical observations that MT interacts with physical function as a factor in healthy aging. PMID- 27194408 TI - Inflammatory insult during pregnancy accelerates age-related behavioral and neurobiochemical changes in CD-1 mice. AB - Data shows that inflammation during pregnancy significantly exerts a long-term influence on offspring, such as increasing the risk of adult cognition decline in animals. However, it is unclear whether gestational inflammation affects the neurobehavioral and neurobiochemical outcomes in the mother-self during aging. In this study, pregnant CD-1 mice intraperitoneally received lipopolysaccharide (LPS) in two doses (25 and 50 g/kg, respectively) or normal saline daily during gestational days 15-17. At the age of 15 months, a battery of behavioral tasks was employed to evaluate their species-typical behaviors, sensorimotor ability, anxiety levels, and spatial learning and memory abilities. An immunohistochemical method was utilized preliminarily to detect neurobiochemical indicators consisting of amyloid-beta, phosphorylated tau, presynaptic proteins synaptotagmin-1 and syntaxin-1, glial fibrillary acidic protein (GFAP), and histone-4 acetylation on the K8 site (H4K8ac). The behavioral results showed that LPS exposure during pregnancy exacerbated a decline in 15-month-old CD-1 mice's abilities to nest, their sensorimotor and spatial learning and memory capabilities, and increased their anxiety levels. The neurobiochemical results indicated that gestational LPS exposure also intensified age-related hippocampal changes, including increased amyloid-beta42, phosphorylated tau, synaptotagmin-1 and GFAP, and decreased syntaxin-1 and H4K8ac. Our results suggested that the inflammatory insult during pregnancy could be an important risk factor for the development of Alzheimer's disease, and the H4K8 acetylation might play an important role in the underlying mechanism. This study offers a perspective for improving strategies that support healthy development and successful aging. PMID- 27194409 TI - Surgical considerations in FAP-related pouch surgery: Could we do better? AB - The ileoanal pouch has become the standard restorative procedure of choice for patients with the classical phenotype in FAP (familial adenomatous polyposis) and also for ulcerative colitis (UC). Whilst we tend to encounter descriptive analyses comparing functional outcome, fertility and quality of life (QOL) between series in literature, there may be an urgent need to discuss the subtle technical modifications that may be pivotal for improving long-term QOL in FAP patients. Our aim is to review the current literature and discuss the aspects of ileal pouch-anal anastomosis that may require specific reevaluation for FAP. Surgical strategies aimed at minimizing post-interventional desmoid growth is one of the most important aspects. For this study, the following topics of interest were selected: Timing of surgery, IRA or ileoanal pouch for classical FAP, laparoscopic or conventional surgery, TME or mesenteric dissection, preservation of the ileocolic vessels, handsewn or double-staple anastomosis, shape and size of pouch, protective ileostomy, Last and definitely not least: how to manage desmoid plaques or desmoids at the time of prophylactic surgery. For the depicted technicalities of the procedure, a review of recent literature was performed and evaluated. For the topics selected, only sparse reference in literature was identified that was focused on the specific condition situation of FAP. Almost all pouch literature focusses on the procedural aspects, and FAP patients are always a very minor number. Therefore it becomes obvious that the specific entity is not adequately taken into account. This is a serious bias for identification of important steps in the procedure that may be beneficial for patients with either of the diseases. The results of this study demonstrate that several technical differences for construction of ileoanal pouches in FAP patients deserve more attention and prospective evaluation-perhaps even randomized trials. The role, importance and potential benefit or deterioration of outcome in most of the discussed technicalities remains unclear to date. Significant differences between the underlying diseases (UC and FAP) have not been taken into consideration, such as specifically the management of precursor desmoid lesions at the time of prophylactic surgery as well as prevention of desmoid tumors. Several of the aspects discussed in this paper should be prospectively evaluated in larger and exclusive series of FAP patients. PMID- 27194411 TI - A tryptophan-containing fluorescent intramolecular complex as a designer peptidic proton sensor. AB - Pyrene and tryptophan groups judiciously placed on a novel molecular scaffold, namely, bispidine exhibited fluorescence due to the formation of an unprecedented emissive intramolecular complex in polar solvents. Upon protonation, the emission signal from the pyrene unit enhances at the expense of the emission signal from the complex. The probe demonstrates good sensitivity, excellent selectivity, and adequate reversibility towards proton sensing. The present design based on the bispidine scaffold opens up newer opportunities for the design of novel bispidine peptide sensors. PMID- 27194410 TI - Increased non-HDL-C level linked with a rapid rate of renal function decline in HIV-infected patients. AB - BACKGROUND: The risk of developing CKD is increased in HIV-infected patients; however, the relationship between renal function decline and lipid abnormalities currently remains unclear in these patients. METHODS: A retrospective cohort study was conducted on 661 HIV-infected patients, whose estimated glomerular filtration rates (eGFRs) were consecutively measured over 6 years. The rate of declines in eGFR per year was calculated, with decreases being evaluated using a linear mixed effect model. The distribution of decreases in eGFR >= 30 % from baseline during the follow-up period was compared across quartiles of non-high density lipoprotein cholesterol (HDL-C) levels using the Cochran-Armitage test. A multivariate logistic regression model was built to examine the relationship between dyslipidemia and decreases in eGFR. RESULTS: The prevalence of CKD increased from 8.5 to 21.2 % during the follow-up. The average of 6 annual eGFR decline rates was 2.01 +/- 0.09 ml/min/1.73 m2/year, which was more than 6-fold higher than that of age-matched controls. The distribution of decreases in eGFR significantly increased across the quartiles of non-HDL-C (p value for trend = 0.0359). Non-HDL-C levels greater than the median value of the cohort were identified as a significant risk factor for decreased eGFR [odds ratio (95 % confidence interval), 1.77 (1.07-3.00)]. CONCLUSION: Increased non-HDL-C levels are a risk factor for renal function decline in HIV-infected patients. PMID- 27194413 TI - Erratum to: 'Multimodal perioperative care plus immunonutrition versus traditional care in total hip arthroplasty: a randomized pilot study'. PMID- 27194412 TI - Cellular and molecular drivers of differential organ growth: insights from the limbs of Monodelphis domestica. AB - A fundamental question in biology is "how is growth differentially regulated during development to produce organs of particular sizes?" We used a new model system for the study of differential organ growth, the limbs of the opossum (Monodelphis domestica), to investigate the cellular and molecular basis of differential organ growth in mammals. Opossum forelimbs grow much faster than hindlimbs, making opossum limbs an exceptional system with which to study differential growth. We first used the great differences in opossum forelimb and hindlimb growth to identify cellular processes and molecular signals that underlie differential limb growth. We then used organ culture and pharmacological addition of FGF ligands and inhibitors to test the role of the Fgf/Mitogen activated protein kinases (MAPK) signaling pathway in driving these cellular processes. We found that molecular signals from within the limb drive differences in cell proliferation that contribute to the differential growth of the forelimb and hindlimbs of opossums. We also found that alterations in the Fgf/MAPK pathway can generate differences in cell proliferation that mirror those observed between wild-type forelimb and hindlimbs of opossums and that manipulation of Fgf/MAPK signaling affects downstream focal adhesion-extracellular matrix (FA-ECM) and Wnt signaling in opossum limbs. Taken together, these findings suggest that evolutionary changes in the Fgf/MAPK pathway could help drive the observed differences in cell behaviors and growth in opossum forelimb and hindlimbs. PMID- 27194414 TI - Moral distress of nursing undergraduates: Myth or reality? AB - INTRODUCTION: During their education process, nursing undergraduates experience ethical conflicts and dilemmas that can lead to moral distress. Moral distress can deprive the undergraduates of their working potential and may cause physical and mental health problems. OBJECTIVE: We investigated the experiences of the undergraduates in order to identify the existence of moral distress caused by ethical conflict and dilemmas experienced during their nursing education. Ethical considerations: This study was designed according to the principles of research with human beings and was approved by the Human Research Ethics Committee. METHOD: A qualitative multiple-case study. Two federal higher education institutions were surveyed, from which 58 undergraduates in nursing participated in the study. The undergraduates were undergoing their professional training. The data were collected through focus groups and were submitted to thematic content analysis, with the resources of the ATLAS TI 7.0 software. RESULTS: Moral distress in undergraduates is a reality and was identified in three axes of analysis: (1) moral distress is experienced by undergraduates in the reality of healthcare services, (2) the teacher as a source of moral distress, and (3) moral distress as a positive experience. CONCLUSION: The undergraduates in nursing manifest moral distress in different stages of their education, particularly during their professional training. The academic community should reflect and seek solutions for the reality of moral distress in undergraduates. PMID- 27194415 TI - A longitudinal analysis of chronic arm morbidity following breast cancer surgery. AB - Arm morbidity (AM) arising from breast cancer (BC) treatment can detrimentally impact quality of life; often limiting a survivor's ability to participate in valued activities. The present study explored (a) the developmental time course of AM [restricted range of motion (ROM), pain, and arm volume changes], negative affect, and perceived disability in the immediate years post-surgery, and (b) the mediating role of perceived disability on the relationship between AM and negative affect over time. In this 5-year longitudinal study, BC survivors from four Canadian oncology clinics (n = 431) completed five annual clinical assessments, where differences in ROM (shoulder abduction, external rotation) and arm volume between the affected and non-affected arm were measured. The profile of mood states (POMS), disability of arm, shoulder, hand, and McGill Pain Questionnaire-Short form were completed. Results from general linear modeling showed that AM, negative affect, and perceived disability were greatest 1-year post-surgery, declined, and with the exception of arm volume changes, were significantly lower 5 years later. Negative affect was significantly associated with restrictions in shoulder abduction and external rotation (average r = -0.15; p < 0.05) and present arm pain (average r = 0.28, p < 0.01) at most assessments. The mediating role of perceived disability on the relationship between AM and negative affect was statistically significant in a majority of assessments. Perceived disability is the underlying factor driving the relationship between AM and mood disturbance over time. Rehabilitative therapy to improve survivors' functional well-being might mitigate the negative impacts of AM on emotional health. PMID- 27194416 TI - Detection of 22q11.2 microduplication by cell-free DNA screening and chromosomal microarray in fetus with multiple anomalies. PMID- 27194417 TI - Synthesis of advanced aluminide intermetallic coatings by low-energy Al-ion radiation. AB - Metals that work at high temperatures (for instance, superalloys in gas-turbines) depend on thermally grown oxide (TGO, commonly alumina) to withstand corrosion attack. Nickel Aluminide (NiAl) as one superior alumina TGO former plays an important role in protective coatings for turbine blades in gas-turbine engines used for aircraft propulsion and power generation. Lowering TGO growth rate is essentially favored for offering sustainable protection, especially in thermal barrier coatings (TBC). However, it can only be achieved currently by a strategy of adding the third element (Pt or reactive elements) into NiAl during traditional diffusion- or deposition-based synthesis of the coating. Here we present a highly flexible Al-ion radiation-based synthesis of advanced NiAl coatings, achieving low TGO growth rate without relying on the third element addition. Our results expand the strategy for lowering TGO growth rate and demonstrate potentials for ion radiation in advancing materials synthesis. PMID- 27194418 TI - Intrinsically aged dermal fibroblasts fail to differentiate into adipogenic lineage. PMID- 27194419 TI - TaZAT8, a C2H2-ZFP type transcription factor gene in wheat, plays critical roles in mediating tolerance to Pi deprivation through regulating P acquisition, ROS homeostasis and root system establishment. AB - Transcription factors (TFs) play critical roles in mediating defense of plants to abiotic stresses through regulating downstream defensive genes. In this study, a wheat C2H2-ZFP (zinc finger protein) type TF gene designated as TaZAT8 was functionally characterized in mediating tolerance to the inorganic phosphate (Pi) starvation stress. TaZAT8 bears conserved motifs harboring in the C2H2-ZFP type counterparts across vascular plant species. The expression of TaZAT8 was shown to be induced in roots upon Pi deprivation, with a Pi concentration- and temporal dependent manner. Overexpression of TaZAT8 in tobacco conferred plants improved tolerance to Pi deprivation; the transgenic lines exhibited enlarged phenotype and elevated biomass and phosphorus (P) accumulation relative to wild-type (WT) after Pi-starvation treatment. NtPT1 and NtPT2, the tobacco phosphate transporter (PT) genes, showed increased transcripts in the Pi-deprived transgenic lines, indicative of their transcriptional regulation by TaZAT8. Overexpression analysis of these PT genes validated their function in mediating Pi acquisition under the Pi deprivation conditions. Additionally, the TaZAT8-overexpressing lines also behaved enhanced antioxidant enzyme (AE) activities and enlarged root system architecture (RSA) with respect to WT. Evaluation of the transcript abundance of tobacco genes encoding AE and PIN proteins, including NtMnSOD1, NtSOD1, NtPOD1;2, NtPOD1;5, NtPOD1;6, and NtPOD1;9, and NtPIN1 and NtPIN4 are upregulated in the TaZAT8-overexpressing lines. Overexpression of NtPIN1 and NtPIN4 conferred plants to enlarged RSA and elevated biomass under the Pi-starvation stress conditions. Our investigation provides insights into plant adaptation to the Pi-starvation stress mediated by distinct ZFP TFs through modulation of Pi acquisition and cellular ROS detoxicity. PMID- 27194420 TI - Comparison of Measured to Predicted Estimations of Nonpoint Source Contaminants Using Conservation Practices in an Agriculturally-Dominated Watershed in Northeast Arkansas, USA. AB - In efforts to reduce nonpoint source runoff and improve water quality, Best Management Practices (BMPs) were implemented in the Outlet Larkin Creek Watershed. Farmers need to make scientifically informed decisions concerning BMPs addressing contaminants from agricultural fields. The BMP Tool was developed from previous studies to estimate BMP effectiveness at reducing nonpoint source contaminants. The purpose of this study was to compare the measured percent reduction of dissolved phosphorus (DP) and total suspended solids to the reported percent reductions from the BMP Tool for validation. Similarities were measured between the BMP Tool and the measured water quality parameters. Construction of a sedimentation pond resulted in 74 %-76 % reduction in DP as compared to 80 % as predicted with the BMP Tool. However, further research is needed to validate the tool for additional water quality parameters. The BMP Tool is recommended for future BMP implementation as a useful predictor for farmers. PMID- 27194421 TI - Bioconcentration of Ag, Cd, Co, Mn and Zn in the Mangrove Oyster (Crassostrea gasar) and Preliminary Human Health Risk Assessment: A Radiotracer Study. AB - Bioaccumulation kinetics of five dissolved metals were determined in the mangrove oyster Crassostrea gasar, using corresponding radiotracers ((54)Mn, (57)Co, (65)Zn, (109)Cd and (110m)Ag). Additionally, their bioaccessibility to human consumers was estimated. Results indicated that over a 14-day exposure (54)Mn and (57)Co were linearly concentrated in oysters whereas (109)Cd, (65)Zn and (110m)Ag were starting to saturate (steady-state not reached). Whole-body concentration factors at 14 days (CF14d in toto) ranged from 187 +/- 65 to 629 +/- 179 with the lowest bioconcentration capacity for Co and the highest for Ag. Depuration kinetics were best described by a double-exponential model with associated biological half-lives ranging from 26 days (Ag) to almost 8 months (Zn and Cd). Bioaccessible fraction of the studied elements was estimated using in vitro digestions, which suggested that oysters consumed seasoned with lemon enhanced the accessibility of Cd, Mn and Zn to human consumers, but not Ag and Co. PMID- 27194422 TI - [The epidemiology of food allergy in Europe]. AB - The interpretation of epidemiological data on food hypersensitivities should clearly separate two issues: the disposition to respond symptomatically to certain foods and the actual reactions occurring, which can be observed only when there is sufficient consumption or targeted exposure/provocation.The exact specification of the case definition is essential for reporting and interpreting food hypersensitivity frequencies. In Europe, prevalence estimates of self reported reactions are reported from 5.7 to 61.6 %, and physician-diagnosed hypersensitivities from 0.2 to 4.2 %. Consideration of only double-blind proven immediate-type reactions gave estimates ranging from 0.0 to 2.2 %. The disposition for severe reactions against food might be less frequent, but cannot be estimated robustly from published data. The only data available for Germany estimates a prevalence of IgE-mediated reactions of 2,5% for Berlin.The most common triggers of early childhood food allergy are cow's milk and hen's egg, which usually cause mild symptoms, limited to the skin. Food allergy aquired in infancy usually disappears by early school age.The European Anaphylaxis Registry documents the spectrum of severe allergic reactions. England has a larger case series for fatal reactions. No incidence can be estimated from either approach, because reporting is voluntary. Additionally, the discussed data does not inform about the clinical relevance of severe allergic reactions against foods.Future systematic studies about the incidence and course of food hypersensitivity should examine sufficiently large groups of people using objective diagnostic criteria. PMID- 27194423 TI - Excision of HIV-1 DNA by gene editing: a proof-of-concept in vivo study. AB - A CRISPR/Cas9 gene editing strategy has been remarkable in excising segments of integrated HIV-1 DNA sequences from the genome of latently infected human cell lines and by introducing InDel mutations, suppressing HIV-1 replication in patient-derived CD4+ T-cells, ex vivo. Here, we employed a short version of the Cas9 endonuclease, saCas9, together with a multiplex of guide RNAs (gRNAs) for targeting the viral DNA sequences within the 5'-LTR and the Gag gene for removing critically important segments of the viral DNA in transgenic mice and rats encompassing the HIV-1 genome. Tail-vein injection of transgenic mice with a recombinant Adeno-associated virus 9 (rAAV9) vector expressing saCas9 and the gRNAs, rAAV:saCas9/gRNA, resulted in the cleavage of integrated HIV-1 DNA and excision of a 978 bp DNA fragment spanning between the LTR and Gag gene in the spleen, liver, heart, lung and kidney as well as in the circulating lymphocytes. Retro-orbital inoculation of rAAV9:saCas9/gRNA in transgenic rats eliminated a targeted segment of viral DNA and substantially decreased the level of viral gene expression in circulating blood lymphocytes. The results from the proof-of concept studies, for the first time, demonstrate the in vivo eradication of HIV-1 DNA by CRISPR/Cas9 on delivery by an rAAV9 vector in a range of cells and tissues that harbor integrated copies of viral DNA. PMID- 27194425 TI - Childhood Maltreatment in the Migraine Patient. AB - OPINION STATEMENT: Maltreatment during childhood increases vulnerability to a host of health disorders, including migraine. Putative mechanisms linking maltreatment and migraine include stress-induced dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, as well as disruption of other stress mediating homeostatic systems, including those involving endocannabinoids, monoamine neurotransmitters, oxytocin, and inflammation. Prolonged elevation of glucocorticoids alters the neural architecture of the limbic system, resulting in the structural as well as functional changes described in both maltreatment and in migraine. Although treatment trials for migraine have not stratified participants by abuse history, strategies, such as cognitive behavioral therapy, which alter stress responsivity, may be particularly effective in this subgroup. Some therapies involving the endocannabinoid, serotonergic, oxytonergic, and inflammatory systems are under investigation for migraine. Anti-epileptic drugs such as valproate and topiramate, which are FDA approved for migraine treatment, are also known to interfere with epigenetic changes induced by stress. Discerning the role for this mechanism in treatment of maltreated migraineurs may introduce another therapeutic avenue. PMID- 27194424 TI - Potassium: friend or foe? AB - The kidney plays an essential role in maintaining homeostasis of ion concentrations in the blood. Because the concentration gradient of potassium across the cell membrane is a key determinant of the membrane potential of cells, even small deviations in serum potassium level from the normal setpoint can lead to severe muscle dysfunction, resulting in respiratory failure and cardiac arrest. Less severe hypo- and hyperkalemia are also associated with morbidity and mortality across various patient populations. In addition, deficiencies in potassium intake have been associated with hypertension and adverse cardiovascular and renal outcomes, likely due in part to the interrelated handling of sodium and potassium by the kidney. Here, data on the beneficial effects of potassium on blood pressure and cardiovascular and renal outcomes will be reviewed, along with the physiological basis for these effects. In some patient populations, however, potassium excess is deleterious. Risk factors for the development of hyperkalemia will be reviewed, as well as the risks and benefits of existing and emerging therapies for hyperkalemia. PMID- 27194428 TI - Irish medical school in Bahrain may breach human rights law. PMID- 27194426 TI - Comparison of anti-anginal effect of cilnidipine with those of nicardipine and nifedipine in the vasopressin-induced angina model of rats. AB - We assessed the anti-anginal effects of cilnidipine in comparison with those of nicardipine and nifedipine (1 and 10 ug/kg, n = 6 for each drug) or vehicle (n = 6) by using the vasopressin-induced angina model of rats. The administration of vasopressin (0.5 IU/kg, i.v.) to the rats depressed the S-wave level of the electrocardiogram reflecting the presence of subendocardial ischemia, whereas it significantly increased the mean blood pressure, resulting in the decrease of the heart rate and the prolongation of the PR interval possibly through a reflex mediated increase in vagal tone. Cilnidipine suppressed the vasopressin-induced depression of the S-wave level in a dose-related manner, which was not observed by nicardipine or nifedipine. In addition, the low dose of cilnidipine hardly affected the vasopressin-induced pressor response, but it attenuated the negative dromotropic effect, suggesting N-type Ca2+ channel inhibition by cilnidipine might have suppressed the parasympathetic nerve activity in vivo like those reported in the sympathetic nerve. Thus, cilnidipine may become a useful strategy for inhibiting coronary vasospasm-induced anginal attack. PMID- 27194427 TI - Comparative assessment of phototherapy protocols for reduction of oxidative stress in partially transected spinal cord slices undergoing secondary degeneration. AB - BACKGROUND: Red/near-infrared light therapy (R/NIR-LT) has been developed as a treatment for a range of conditions, including injury to the central nervous system (CNS). However, clinical trials have reported variable or sub-optimal outcomes, possibly because there are few optimized treatment protocols for the different target tissues. Moreover, the low absolute, and wavelength dependent, transmission of light by tissues overlying the target site make accurate dosing problematic. RESULTS: In order to optimize light therapy treatment parameters, we adapted a mouse spinal cord organotypic culture model to the rat, and characterized myelination and oxidative stress following a partial transection injury. The ex vivo model allows a more accurate assessment of the relative effect of different illumination wavelengths (adjusted for equal quantal intensity) on the target tissue. Using this model, we assessed oxidative stress following treatment with four different wavelengths of light: 450 nm (blue); 510 nm (green); 660 nm (red) or 860 nm (infrared) at three different intensities: 1.93 * 10(16) (low); 3.85 * 10(16) (intermediate) and 7.70 * 10(16) (high) photons/cm(2)/s. We demonstrate that the most effective of the tested wavelengths to reduce immunoreactivity of the oxidative stress indicator 3-nitrotyrosine (3NT) was 660 nm. 860 nm also provided beneficial effects at all tested intensities, significantly reducing oxidative stress levels relative to control (p <= 0.05). CONCLUSIONS: Our results indicate that R/NIR-LT is an effective antioxidant therapy, and indicate that effective wavelengths and ranges of intensities of treatment can be adapted for a variety of CNS injuries and conditions, depending upon the transmission properties of the tissue to be treated. PMID- 27194429 TI - Adipocytes Viability After Suction-Assisted Lipoplasty: Does the Technique Matter? AB - BACKGROUND: Suction-assisted lipoplasty (SAL; liposuction) is an established aesthetic procedure in plastic surgery. The main parameters differentiating one method of lipoplasty from another are safety, consistency of results, and other more technical parameters. Due to the recent popularity of lipotransfer, the quality of extracted fat has become a relevant parameter. We compare the viability of extracted adipocytes after dry SAL, hyper-tumescent PAL (power assisted lipoplasty), and water-assisted lipoplasty (WAL). METHODS: We used fluorescent microscopy to differentiate viable from necrotic/apoptotic cells after liposuction using each of the mentioned methods. RESULTS: The ratio of living cells between the three methods was significantly different with dry liposuction yielding inferior ratios (p = 0.011). When omitting extreme results, we found that the body-jet technique (WAL) yielded higher ratios of living cells than the hyper-tumescent technique (p < 0.001). The total number of cells was highest in the hyper-tumescent method (p = 0.013). CONCLUSIONS: Our results indicate that the hyper-tumescent technique yields the highest number of cells, whereas the body-jet technique yields the highest living cells ratio. The dry technique is clearly inferior to both. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . PMID- 27194430 TI - Whole Blood Viscosity and Cardiovascular Diseases: A Forgotten Old Player of the Game. PMID- 27194431 TI - Pheochromocytoma in Old World Primates (Macaca mulatta and Chlorocebus aethiops). AB - Pheochromocytoma, a rarely reported adrenal gland neoplasm in Old World primates, was diagnosed in 5 rhesus macaques (Macaca mulatta) and 2 African green monkeys (Chlorocebus aethiops) from 3 research institutions. Age and sex were available for 6 primates. Two males and 4 females were affected, ranging in age from 9 to 31 years. All neoplasms were unilateral and, in the cases reporting the affected gland, 4 involved the right adrenal gland and 2 involved the left. Diagnosis was established by characteristic histologic features. Immunohistochemically, neoplastic cells in all cases expressed chromogranin A and met-enkephalin and were negative for melan-A and inhibin. Six of 7 tumors were positive for beta endorphin. Pulmonary metastases were present in 2 rhesus macaques and portal vein invasion in 1 African green monkey. To the authors' knowledge, this is the first report of malignant pheochromocytoma in Old World primates. PMID- 27194432 TI - No association between dysplasminogenemia with p.Ala620Thr mutation and atypical hemolytic uremic syndrome. AB - Atypical hemolytic uremic syndrome (aHUS), a form of thrombotic microangiopathy, is caused by the uncontrolled activation of the alternative pathway of complement on the cell surface that leads to microangiopathic hemolytic anemia, thrombocytopenia, and renal failure. A recent genetic analysis of aHUS patients identified deleterious mutations not only in complement or complement regulatory genes but also in the plasminogen gene, suggesting that subnormal plasminogen activity may be related to the degradation of thrombi in aHUS. Dysplasminogenemia, which is caused by a genetic variant in the plasminogen gene, PLG:p.Ala620Thr, is commonly observed in the northeast Asian populations, including Japanese. To examine the association between dysplasminogenemia and aHUS, we genotyped PLG:p.Ala620Thr in 103 Japanese patients with aHUS. We identified five aHUS patients with PLG:p.Ala620Thr; the minor allele frequency (MAF) was thus 0.024. The MAF in the patient group was not significantly different from those obtained from a general Japanese population (MAF = 0.020) and the Japanese genetic variation HGDV database (MAF = 0.021) (P = 0.62 and 0.61, respectively). We concluded that, although carriers with PLG:p.Ala620Thr show low plasminogen activity, this is not a predisposing variant for aHUS and that individuals of dysplasminogenemia are not at significantly increased risk of aHUS. PMID- 27194433 TI - Reversible Pharmacological Induction of Motor Symptoms in MPTP-Treated Mice at the Presymptomatic Stage of Parkinsonism: Potential Use for Early Diagnosis of Parkinson's Disease. AB - A crucial event in the pathogenesis of Parkinson's disease is the death of dopaminergic neurons of the nigrostriatal system, which are responsible for the regulation of motor function. Motor symptoms first appear in patients 20-30 years after the onset of the neurodegeneration, when there has been a loss of an essential number of neurons and depletion of compensatory reserves of the brain, which explains the low efficiency of treatment. Therefore, the development of a technology for the diagnosing of Parkinson's disease at the preclinical stage is of a high priority in neurology. In this study, we have developed at an experimental model a fundamentally novel for neurology approach for diagnosis of Parkinson's disease at the preclinical stage. This methodology, widely used for the diagnosis of chronic diseases in the internal medicine, is based on the application of a challenge test that temporarily increases the latent failure of a specific functional system, thereby inducing the short-term appearance of clinical symptoms. The provocation test was developed by a systemic administration of alpha-methyl-p-tyrosine (alphaMpT), a reversible inhibitor of tyrosine hydroxylase to MPTP-treated mice at the presymptomatic stage of parkinsonism. For this, we first selected a minimum dose of alphaMpT, which caused a decrease of the dopamine level in the striatum of normal mice below the threshold at which motor dysfunctions appear. Then, we found the maximum dose of alphaMpT at which a loss of dopamine in the striatum of normal mice did not reach the threshold level, and motor behavior was not impaired. We showed that alphaMpT at this dose induced a decrease of the dopamine concentration in the striatum of MPTP-treated mice at the presymptomatic stage of parkinsonism below a threshold level that results in the impairment of motor behavior. Finally, we proved that alphaMpT exerts a temporal and reversible influence on the nigrostriatal dopaminergic system of MPTP-treated mice with no long-term side effects on other catecholaminergic systems. Thus, the above experimental data strongly suggest that alphaMpT-based challenge test might be considered as the provocation test for Parkinson's disease diagnosis at the preclinical stage in the future clinical trials. PMID- 27194434 TI - Stiffness as a Risk Factor for Achilles Tendon Injury in Running Athletes. AB - BACKGROUND: Overuse injuries are multifactorial resulting from cumulative loading. Therefore, clear differences between normal and at-risk individuals may not be present for individual risk factors. Using a holistic measure that incorporates many of the identified risk factors, focusing on multiple joint movement patterns may give better insight into overuse injuries. Lower body stiffness may provide such a measure. OBJECTIVE: To identify how risk factors for Achilles tendon injuries influence measures of lower body stiffness. METHODS: SPORTDiscus, Web of Science, CINAHL and PubMed were searched for Achilles tendon injury risk factors related to vertical, leg and joint stiffness in running athletes. RESULTS: Increased braking force and low surface stiffness, which were clearly associated with increased risk of Achilles tendon injuries, were also found to be associated with increased lower body stiffness. High arches and increased vertical and propulsive forces were protective for Achilles tendon injuries and were also associated with increased lower body stiffness. Risk factors for Achilles tendon injuries that had unclear associations were also investigated with the evidence trending towards an increase in leg stiffness and a decrease in ankle stiffness being detrimental to Achilles tendon health. CONCLUSION: Few studies have investigated the link between lower body stiffness and Achilles injury. High stiffness is potentially associated with risk factors for Achilles tendon injuries although some of the evidence is controversial. Prospective injury studies are needed to confirm this relationship. Large amounts of high-intensity or high-speed work or running on soft surfaces such as sand may increase Achilles injury risk. Coaches and clinicians working with athletes with new or reoccurring injuries should consider training practices of the athlete and recommend reducing speed or sand running if loading is deemed to be excessive. PMID- 27194436 TI - Ultrasound follow-up in a patient with intestinal obstruction due to post traumatic intramural duodenal hematoma. AB - We report the case of a 7-year-old girl with intestinal obstruction due to post traumatic intramural duodenal hematoma. She had fallen from the monkey bars the day before presenting to our hospital, and was admitted with signs of abdominal pain, vomiting, and nausea. Abdominal ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI) demonstrated a heterogeneous solid mass located within the duodenal wall, compressing the descending part of the duodenum. The inferior vena cava was also compressed by the mass lesion, although no associated symptoms were evident. Based on these findings, the mass lesion was considered to represent intramural hematoma causing intestinal obstruction. She was managed conservatively with total parenteral nutrition. Although CT and MRI are useful for differentiating hematoma from other intestinal tumors, ultrasonography is minimally invasive and easier to perform repeatedly. In case of duodenal hematoma, ultrasonography may be quite helpful for diagnosis and follow-up by monitoring tumor size and characteristics, and the degree of duodenal compression during conservative treatment. PMID- 27194435 TI - Discordant CSF/plasma HIV-1 RNA in patients with unexplained low-level viraemia. AB - The central nervous system has been proposed as a sanctuary site where HIV can escape antiretroviral control and develop drug resistance. HIV-1 RNA can be at higher levels in CSF than plasma, termed CSF/plasma discordance. We aimed to examine whether discordance in CSF is associated with low level viraemia (LLV) in blood. In this MRC-funded multicentre study, we prospectively recruited patients with LLV, defined as one or more episode of unexplained plasma HIV-1 RNA within 12 months, and undertook CSF examination. Separately, we prospectively collected CSF from patients undergoing lumbar puncture for a clinical indication. Patients with durable suppression of viraemia and no evidence of CNS infection were identified as controls from this group. Factors associated with CSF/plasma HIV-1 discordance overall were examined. One hundred fifty-three patients were recruited across 13 sites; 40 with LLV and 113 undergoing clinical lumbar puncture. Seven of the 40 (18 %) patients with LLV had CSF/plasma discordance, which was significantly more than 0/43 (0 %) with durable suppression in blood from the clinical group (p = 0.005). Resistance associated mutations were shown in six CSF samples from discordant patients with LLV (one had insufficient sample for testing), which affected antiretroviral therapy at sampling in five. Overall discordance was present in 20/153 (13 %) and was associated with nadir CD4 but not antiretroviral concentrations in plasma or CSF. CSF/plasma discordance is observed in patients with LLV and is associated with antiretroviral resistance associated mutations in CSF. The implications for clinical practice require further investigation. PMID- 27194437 TI - UltraPro Hernia System, Prolene Hernia System and Lichtenstein for primary inguinal hernia repair: 3-year outcomes of a prospective randomized controlled trial. AB - PURPOSE: Chronic pain and discomfort are common after inguinal hernia repair (IHR). In this study, results from a 3-year follow-up from a randomized controlled study comparing three different mesh repairs for postoperative pain, discomfort, Quality of Life (QoL) and patient satisfaction are reported. METHODS: Between November 1, 2006 and January 31, 2009, 309 men, who underwent day surgery for primary unilateral inguinal hernia under local anesthesia, were randomized to three different mesh repairs; UltraPro Hernia System (U), Prolene Hernia System (P) and Lichtenstein procedure (L). RESULTS: Preoperatively, there were no differences between groups regarding demographics, symptoms, inguinal pain or QoL (SF-36 and a hernia-specific questionnaire). Operating time, postoperative pain, complications and time to full recovery were similar. At 36 months, 21 patients indicated pain [L, n = 6, P, n = 6 and U, n = 9; VAS (median (IQR)): L 0.4 (0.2 1.7), P 0.2 (0.1-2.3) and U 1.6 (0.7-4.6), p = ns]. Physical QoL was reduced in all groups before surgery and was similarly increased to normal levels after 3 months without further changes throughout the study. Although 92 % of participants were satisfied, sixteen percent reported any discomfort from the groin (ns between groups). Five recurrences were reported (L, n = 2, P, n = 1 and U, n = 2, p = ns). CONCLUSIONS: After 3 years of follow-up, all three procedures provided equally good results regarding, pain, discomfort and QoL and could therefore be recommended for primary IHR in LA. PMID- 27194439 TI - Psychosocial Risk Factors Related to Ischemic Heart Disease in Women. AB - BACKGROUND: Psychosocial risk factors such as stress and psychiatric disorders are known to have negative impacts on health outcomes, but their effects on ischemic heart disease, particularly in women, remain to be fully understood despite contributing to one-third of the population attributable risk in acute myocardial infarction. METHODS: The impact of stress, social isolation, low socioeconomic status, hostility and anger, and stress-related psychiatric disorders on cardiovascular outcomes and the potential mechanisms that underlie their association with ischemic heart disease, with a focus on women, is evaluated. Online search of relevant terms, including the aforementioned risk factors, women, and ischemic heart disease, was utilized to find recent and pertinent trials. RESULTS: Psychosocial risk factors increase cardiovascular risk in both women and men. However, current literature points to a greater degree of adverse cardiovascular events in women who experience these risk factors than in men, but the literature is not as well-defined as the data regarding traditional risk factors and cardiovascular disease. CONCLUSION: Dedicated study of the sex differences in ischemic heart disease incidence and recurrence, including the impact of psychosocial risk factors, is warranted for the development of appropriate gender-specific diagnostic testing and treatment options in heart disease. PMID- 27194440 TI - The Impact of Small Heat Shock Proteins (HspBs) in Alzheimer's and Other Neurological Diseases. AB - BACKGROUND: Heat shock proteins are powerful endogenous cytoprotective proteins which help cells to survive recurrent cellular stress events. Identifying the underlying molecular mechanisms and molecular targets is especially interesting since it may help to develop new therapeutic strategies for the treatment of diseases. OBJECTIVE: This review will focus on the group of small heat shock proteins, also named HspBs. HspBs play an important role in various neurological diseases. Most neurodegenerative diseases are characterized by a distinct pathology with accumulation and aggregation of misfolded proteins, such as deposits of amyloid plaques or neurofibrillary tangles in Alzheimer's disease. Such pathological protein aggregates are thought to lead to cellular dysfunction and finally to cell death. HspBs display chaperone-like functions and are able to prevent protein aggregation by which they may slow down progression of these diseases. However, HspBs have multiple additional functions which also may contribute to neuroprotection. RESULTS/CONCLUSIONS: In this review we will first give an overview of the HspB protein family, their structure, functions and expression pattern. Then we will highlight their impact in the brain, in neurodegenerative diseases and especially in Alzheimer's disease and try to unravel their multifactorial effects in several aspects of the disease pathologies. PMID- 27194441 TI - Protein Amyloidogenesis Investigated by Small Angle Scattering. AB - In the last decades, the study of the mechanisms inducing amyloid fibril formation has involved several experimental and theoretical biophysical approaches. Many efforts have been made by scientist at the borderline between biology, chemistry, biochemistry and physics in order to understand why and in which way a protein starts its amyloidogenic pattern. This fundamental research issue is evolving in parallel to the development of drugs and inhibitors able to modify protein self assembly towards amyloid fibrils. Small angle xray and neutron scattering experiments represent suitable methods to investigate protein amyloidogenesis and the possible effects of inhibitors: they are in-solution techniques, require low amount of sample and their time-resolution makes it possible to follow aggregation pattern. In this paper we review small angle x-ray and neutron scattering studies dedicated to investigate amyloid beta peptide and alpha-synuclein, related to Alzheimer's and Parkinson's diseases, respectively, together with some other studies that introduced innovative models to describe with small angle scattering techniques amyloid fibrillation processes. PMID- 27194438 TI - Pulmonary arterial hypertension in children: diagnosis using ratio of main pulmonary artery to ascending aorta diameter as determined by multi-detector computed tomography. AB - BACKGROUND: The ratio of the transverse diameter of the main pulmonary artery (MPA) to ascending aorta as determined at multi-detector CT is a tool that can be used to assess the pulmonary arterial size in cases of pulmonary arterial hypertension in children. OBJECTIVE: To establish a ratio of MPA to ascending aorta diameter using multi-detector CT imaging suggestive of pulmonary arterial hypertension in children. We hypothesize that a defined ratio of MPA to ascending aorta is identifiable on multi-detector CT and that higher ratios can be used to reliably diagnose the presence of pulmonary arterial hypertension in children. MATERIALS AND METHODS: We calculated the multi-detector CT ratio of MPA to ascending aorta diameter in 44 children with documented pulmonary arterial hypertension by right heart catheterization and in 44 age- and gender-matched control children with no predisposing factors for pulmonary arterial hypertension. We compared this multi-detector-CT-determined ratio with the MPA pressure in the study group, as well as with the ratio of MPA to ascending aorta in the control group. A threshold ratio value was calculated to accurately identify children with pulmonary arterial hypertension. RESULTS: Children with documented primary pulmonary arterial hypertension have a significantly higher ratio of MPA to ascending aorta (1.46) than children without pulmonary arterial hypertension (1.11). A ratio of 1.3 carries a positive likelihood of 34 and a positive predictive value of 97% for the diagnosis of pulmonary arterial hypertension. CONCLUSION: The pulmonary arteries were larger in children with pulmonary arterial hypertension than in a control group of normal children. A CT measured ratio of MPA to ascending aorta of 1.3 should raise the suspicion of pulmonary arterial hypertension in children. PMID- 27194442 TI - Supercritical Water as Nanomedium for Gasification of Lignite-Water Suspension. AB - The gasification of an aqueous suspension of lignite from Alexandria coalfield (Ukraine) under the supercritical pressure was studied. The initial rates of the formation of hydrogen, carbon dioxide and methane were evaluated. The mutually stimulating interaction of the components of "brown coal-water-mineral matter" system was shown due to the influence of nanoscaled water medium on the formation of dipole-inductive, dispersive and ionic associates. In the temperature range of 300-450 degrees C, the oxygen source for gaseous products of the lignite supercritical gasification is mainly ion-associative nanoclustered water. The source of hydrogen at the subcritical temperature is the organic part of brown coal. For the supercritical water, the source of H is the nanoscale medium with ion associates. The last ones were responsible for the further transformation of coal. PMID- 27194443 TI - Strength Improvement of Glass Substrates by Using Surface Nanostructures. AB - Defects and heterogeneities degrade the strength of glass with different surface and subsurface properties. This study uses surface nanostructures to improve the bending strength of glass and investigates the effect of defects on three glass types. Borosilicate and aluminosilicate glasses with a higher defect density than fused silica exhibited 118 and 48 % improvement, respectively, in bending strength after surface nanostructure fabrication. Fused silica, exhibited limited strength improvement. Therefore, a 4-MUm-deep square notch was fabricated to study the effect of a dominant defect in low defect density glass. The reduced bending strength of fused silica caused by artificial defect increased 65 % in the presence of 2-MUm-deep nanostructures, and the fused silica regained its original strength when the nanostructures were 4 MUm deep. In fragmentation tests, the fused silica specimen broke into two major portions because of the creation of artificial defects. The number of fragments increased when nanostructures were fabricated on the fused silica surface. Bending strength improvement and fragmentation test confirm the usability of this method for glasses with low defect densities when a dominant defect is present on the surface. Our findings indicate that nanostructure-based strengthening is suitable for all types of glasses irrespective of defect density, and the observed Weibull modulus enhancement confirms the reliability of this method. PMID- 27194444 TI - Hierarchical Heterostructures of NiCo2O4@XMoO4 (X = Ni, Co) as an Electrode Material for High-Performance Supercapacitors. AB - Hierarchical heterostructures of NiCo2O4@XMoO4 (X = Ni, Co) were developed as an electrode material for supercapacitor with improved pseudocapacitive performance. Within these hierarchical heterostructures, the mesoporous NiCo2O4 nanosheet arrays directly grown on the Ni foam can not only act as an excellent pseudocapacitive material but also serve as a hierarchical scaffold for growing NiMoO4 or CoMoO4 electroactive materials (nanosheets). The electrode made of NiCo2O4@NiMoO4 presented a highest areal capacitance of 3.74 F/cm(2) at 2 mA/cm(2), which was much higher than the electrodes made of NiCo2O4@CoMoO4 (2.452 F/cm(2)) and NiCo2O4 (0.456 F/cm(2)), respectively. Meanwhile, the NiCo2O4@NiMoO4 electrode exhibited good rate capability. It suggested the potential of the hierarchical heterostructures of NiCo2O4@CoMoO4 as an electrode material in supercapacitors. PMID- 27194445 TI - Myelin Sheath Development in the Maxillary Nerve of the Newborn Pig. AB - Myelination, the ensheathing of neuronal axons by myelin, is important for the proper function of both central and peripheral nervous systems. Various studies have investigated the quantitative parameters of myelination in certain species. Pigs are among the species of which their use as laboratory animals in neuroscience research increased the past few decades. However, there is limited data regarding the myelination process in the pig. Moreover, the maxillary nerve is crucial for Pseudorabies Virus (PrV) neuropathogenesis. In this context, a quantitative analysis of various myelination parameters of the maxillary nerve was performed, during the first 5 weeks of porcine post-natal development, the time period, which exhibits the highest interest for PrV neuropathogenesis. The evaluation was conducted in four groups of uninfected pigs, at the time of birth (group 0w), at the age of 1 week (group 1w), 3 weeks (group 3w) and 5 weeks (group 5w), using toluidine blue staining, immunofluorescence and electron microscopy. Axon and fibre diameter, perimeter and surface, myelin sheath thickness and g-ratio were measured on histological sections transverse to the longitudinal axis of the maxillary nerve. The thickness of myelin sheath was 0.76 MUm for group 0w, 0.94 MUm for group 1w, 0.98 MUm for group 3w and 1.03 MUm for group 5w. The g-ratio was 0.529, 0.540, 0.542 and 0.531 for the respective animal groups. The results of this study contribute to the understanding of the myelination process in the pig will be used for the study of PrV effects on the myelination development of newborn piglets' maxillary nerve and may shed new light to their vulnerability to the virus. PMID- 27194446 TI - Chitosan/Chondroitin Sulfate Membranes Produced by Polyelectrolyte Complexation for Cartilage Engineering. AB - Membranes made of chitosan (CHT) and chondroitin sulfate (CS) are herein presented using a polyelectrolyte complexation sedimentation/evaporation method. The membranes present high roughness and heterogeneous morphology induced by salt crystals. Exposing the membranes to different salt concentrations induces saloplastic behavior, as shown by an increasing water absorption and decreasing stiffness while exposed to increasing concentrations of salt. Establishing contact between two parts of a cut membrane leads to their self-adhesion and maintenance of their stretching ability. The membranes sustain the adhesion of ATDC5 prechondrocyte cells, inducing their rearrangement in cellular aggregates typical of chondrogenesis, and the expression of cartilage markers. Impregnated TGF-beta3 remains loaded after 14 days of incubation, releasing only 1.2% of its total loaded mass. CHT/CS polyelectrolyte membranes are here shown as suitable candidates for the biomedical field, namely, for cartilage regeneration. PMID- 27194448 TI - Leishmaniasis, conflict, and political terror: A spatio-temporal analysis. AB - BACKGROUND: Leishmaniasis has been estimated to cause the ninth largest burden amongst global infectious diseases. Occurrence of the disease has been anecdotally associated with periods of conflict, leading to its referral as a disease of 'guerrilla warfare.' Despite this, there have been few studies that quantitatively investigate the extent to which leishmaniasis coincides with conflict or political terror. METHODOLOGY: This study employed a longitudinal approach to empirically test for an association between cutaneous and visceral leishmaniasis incidence with occurrence of conflict and political terror at the national level, annually for 15 years (1995-2010). Leishmaniasis incidence data were collected for 54 countries, and combined with UCDP/PRIO Armed Conflict and Amnesty International political terror datasets. Mixed effects negative binomial regression models clustered at the country-level were constructed to evaluate the incidence rate ratios against the predictors, while controlling for wealth. Additionally, to understand how and why conflict-terror may be associated with leishmaniasis incidence, we conducted a historical analysis. We identify and discuss posited causal mechanisms in the literature, and critically assessed pathways by which leishmaniasis might occur in places and times of conflict terror. RESULTS: There was a significant dose-response relationship for disease incidence based on increasing levels of conflict and terror. Country-years experiencing very high levels of conflict-terror were associated with a 2.38 times higher [95% CI: 1.40-4.05] and 6.02 times higher [95% CI: 2.39-15.15] incidence of cutaneous and visceral leishmaniasis, respectively. Historical analysis indicated that conflict and terror contribute to-or coincide with leishmaniasis incidence through processes of population displacement and health system deterioration. CONCLUSIONS: This research highlights the potentially increased risks for cutaneous and visceral leishmaniasis incidence in areas of high conflict-terror. Notably, conflict-terror may act as an empirical proxy for indirect and concomitant processes of social breakdown, migration, and instability, which emerge as the dominant processes associated with disease incidence. PMID- 27194447 TI - Clinical significance of BRAF mutation status in circulating tumor DNA of metastatic melanoma patients at baseline. AB - Circulating tumor DNA is a promising non-invasive tool for cancer monitoring. The main objective of our work was to investigate the relationship between mutant BRAF DNA in plasma and clinical response. Thirty-eight stage IV patients with a V600 mutated BRAF melanoma were included prior to any treatment. DNA was extracted from plasma and mutant DNA was detected using the amplification refractory mutation system method. Before the beginning of any treatment, the corresponding BRAF mutation was detected in 29 of the 38 tested plasma samples (76.3% positive per cent agreement). We observed a strong correlation between the presence of circulating mutated DNA and overall survival (OS; P=.02), and with the number of metastatic sites (P=.01). The presence of circulating mutated DNA was also strongly correlated with serum LDH activity (P<.01) and S100 protein concentration (P<.01). Finally, seven patients presented discordant BRAF status in different tumor sites. In all these patients, the test performed on ctDNA was positive, suggesting that ctDNA analysis might be less sensitive to tumor heterogeneity. Altogether, these results suggest that plasmatic mutant BRAF DNA is a prognostic factor of OS, correlated with tumor burden. In addition, it represents an interesting alternative source of DNA to detect BRAF mutations before treatment. PMID- 27194450 TI - A retrospective review of cyproheptadine for feeding intolerance in children less than three years of age: effects and side effects. AB - AIM: Premature infants and those with brain injury often suffer from feeding intolerance and vomiting in the first several years of life. Cyproheptadine is a medication with antihistaminergic, antiserotonergic and anticholinergic effects, thought to increase gastric accommodation. We aimed to retrospectively review our experience using cyproheptadine for feeding intolerance and/or vomiting in children under the age of three. METHODS: This is a retrospective chart review of 39 patients less than three years of age who were prescribed cyproheptadine for feeding intolerance or vomiting and had follow-up information available. RESULTS: Starting dose ranged widely (from 0.069 to 0.825 mg/kg/day). Side effects such as sleepiness and constipation were rare. The medication had a significant positive effect, defined as resolution of vomiting, improved feeding tolerance or improved comfort with feeds, in 67% of children. An additional 28% showed possible improvement, defined as some improvement in vomiting or improvement in vomiting or feeding tolerance in conjunction with other changes in addition to cyproheptadine. CONCLUSION: In our experience, cyproheptadine appears to be safe and effective in decreasing vomiting and feeding intolerance in children less than three years of age. A trial of cyproheptadine could be considered before invasive testing in infants with feeding issues. PMID- 27194449 TI - A rationally engineered yeast pyruvyltransferase Pvg1p introduces sialylation like properties in neo-human-type complex oligosaccharide. AB - Pyruvylation onto the terminus of oligosaccharide, widely seen from prokaryote to eukaryote, confers negative charges on the cell surface and seems to be functionally similar to sialylation, which is found at the end of human-type complex oligosaccharide. However, detailed molecular mechanisms underlying pyruvylation have not been clarified well. Here, we first determined the crystal structure of fission yeast pyruvyltransferase Pvg1p at a resolution of 2.46 A. Subsequently, by combining molecular modeling with mutational analysis of active site residues, we obtained a Pvg1p mutant (Pvg1p(H168C)) that efficiently transferred pyruvyl moiety onto a human-type complex glycopeptide. The resultant pyruvylated human-type complex glycopeptide recognized similar lectins on lectin arrays as the alpha2,6-sialyl glycopeptides. This newly-generated pyruvylation of human-type complex oligosaccharides would provide a novel method for glyco bioengineering. PMID- 27194452 TI - Dynamics of chemical vapor sensing with MoS2 using 1T/2H phase contacts/channel. AB - Ultra-thin transition metal dichalcogenides (TMDs) films show remarkable potential for use in chemical vapor sensing devices. Electronic devices fabricated from TMD films are inexpensive, inherently flexible, low-power, amenable to industrial-scale processing because of emergent growth techniques, and have shown high sensitivity and selectivity to electron donor analyte molecules important for explosives and nerve gas detection. However, for devices reported to date, the conductance response to chemical vapors is dominated by Schottky contacts, to the detriment of the sensitivity, selectivity, recovery, and obscuring their intrinsic behavior. Here, we use contact engineering to transition the contacts in a MoS2 FET-based chemical vapor sensor to the 1T conducting phase, while leaving the channel in the 2H semiconducting state, and thus providing Ohmic contacts to the film. We demonstrate that the resultant sensors have much improved electrical characteristics, are more selective, and recover fully after chemical vapor exposure-all major enhancements to previously MoS2 sensor devices. We identify labile nitrogen-containing electron donors as the primary species that generate a response in MoS2, and we study the dynamics of the sensing reactions, identifying two possible qualitative models for the chemical sensing reaction. PMID- 27194451 TI - Cell-cell contact and matrix adhesion promote alphaSMA expression during TGFbeta1 induced epithelial-myofibroblast transition via Notch and MRTF-A. AB - During epithelial-mesenchymal transition (EMT) epithelial cells lose cell-cell adhesion, exhibit morphological changes, and upregulate the expression of cytoskeletal proteins. Previous studies have demonstrated that complete disruption of cell-cell contact can promote transforming growth factor (TGF) beta1-induced EMT and the expression of the myofibroblast marker alpha smooth muscle actin (alphaSMA). Furthermore, increased cell spreading mediates TGFbeta1 induced alphaSMA expression during EMT. Here, we sought to examine how the presence of partial cell-cell contacts impacts EMT. A microfabrication approach was employed to decouple the effects of cell-cell contact and cell-matrix adhesion in TGFbeta1-induced EMT. When cell spreading is controlled, the presence of partial cell-cell contacts enhances expression of alphaSMA. Moreover, cell spreading and intercellular contacts together control the subcellular localization of activated Notch1 and myocardin related transcription factor (MRTF)-A. Knockdown of Notch1 or MRTF-A as well as pharmacological inhibition of these pathways abates the cell-cell contact mediated expression of alphaSMA. These data suggest that the interplay between cell-matrix adhesion and intercellular adhesion is an important determinant for some aspects of TGFbeta1 induced EMT. PMID- 27194453 TI - Knee joint angle and vasti muscle electromyograms during fatiguing contractions. AB - We compared vasti muscle electromyograms for two knee joint angles during fatiguing tetanic contractions. Tetanic contraction of the knee extensors was evoked for 70 s by electrical stimulation of the femoral nerve at knee joint angles of 60 degrees (extended, with 0 degrees indicating full extension) and 110 degrees (flexed) in eight healthy men. Surface electromyography was recorded from the vastus intermedius (VI), vastus lateralis (VL) and vastus medialis (VM) muscles. Knee extension force and M-wave amplitudes and durations were calculated every 7 s, which were normalized by the initial value. Normalized knee extension force was decreased at the flexed knee joint angle compared with that of the extended knee joint angle (P<0.05). Decreased normalized M-wave amplitude and increased normalized M-wave duration of the VI were greater at the flexed knee joint angle than the extended knee joint angle (P<0.05), whereas those for the VL and VM were similar (P>0.05). These results suggest that peripheral fatigue profiles of the VI might be greater at the flexed than the extended knee joint angles, but that of VL and VM might be similar in the tested range of knee joint angles (i.e. 60 degrees -110 degrees ) during continuous tetanic contraction induced by electrical stimulation. Therefore, greater reduction of knee extension force at the flexed knee joint angle than the extended knee joint angle may reflect fatigue development of the VI more than other quadriceps femoris components. PMID- 27194454 TI - Engineering protein interfaces yields ferritin disassembly and reassembly under benign experimental conditions. AB - Ferritin nanocages are promising platforms for drug encapsulation. However, extreme conditions (pH <= 2) required for dissociation limit their application. Here, we engineered protein interfaces to yield ferritin nanocages which disassemble at pH 4.0 and reassemble at pH 7.5. During this process, bioactive molecules can be encapsulated within the protein cavity. PMID- 27194455 TI - One-Pot Synthesis of 2,4,5-Trisubstituted Imidazoles via [2 + 2 + 1] Cycloannulation of 1,3-Bishet(aryl)-monothio-1,3-diketones, alpha-Substituted Methylamines and Sodium Nitrite through alpha-Nitrosation of Enaminones. AB - An efficient one-pot synthesis of a series of diversely functionalized trisubstituted 4(5)het(aroyl)-2,5(4)-het(aryl)/alkylimidazoles from readily available 1,3-bishet(aryl)monothio-1,3-diketones has been reported. This novel sequential one-pot, three step protocol, wherein three new carbon nitrogen bonds are formed in contiguous fashion, involves in situ generation of enaminones by reaction of monothio-1,3-diketones with alpha-substituted methylamines, followed by their alpha-nitrosation with sodium nitrite and subsequent base mediated intramolecular heterocyclization of the resulting alpha-hydroxyiminoimines to trisubstituted imidazoles in high yields under mild conditions. These newly prepared 4(5)-het(aroyl)-5(4)-het(aryl)/alkylimidazoles are shown to exist as tautomeric mixture, however, their subsequent alkylation with methyl iodide in the presence of potassium carbonate affords 1-N-methy-2,5-bishet(aryl)-4 het(aroyl)imidazoles in highly regioselective fashion in most of the cases. Synthesis of few 4(5)-(2-hydroxyphenyl)-2,5(4)-substituted imidazoles, which are known to be good coordinating ligands, has also been reported. A probable mechanism for the formation of these imidazoles from hydroxyiminoimine intermediates has also been suggested. PMID- 27194457 TI - HSI colour-coded analysis of scattered light of single plasmonic nanoparticles. AB - Single plasmonic nanoparticles (PNPs) analysis with dark-field microscopic imaging (iDFM) has attracted much attention in recent years. The ability for quantitative analysis of iDFM is critical, but cumbersome, for characterizing and analyzing the scattered light of single PNPs. Here, a simple automatic HSI colour coding method is established for coding dark-field microscopic (DFM) images of single PNPs with localized surface plasmon resonance (LSPR) scattered light, showing that hue value in the HSI system can realize accurate quantitative analysis of iDFM and providing a novel approach for quantitative chemical and biochemical imaging at the single nanoparticle level. PMID- 27194456 TI - Exploring the Utility of Web-Based Social Media Advertising to Recruit Adult Heavy-Drinking Smokers for Treatment. AB - BACKGROUND: Identifying novel ways to recruit smokers for treatment studies is important. In particular, certain subgroups of adult smokers, such as heavy drinking smokers, are at increased risk for serious medical problems and are less likely to try quitting smoking, so drawing this hard-to-reach population into treatment is important for improving health outcomes. OBJECTIVE: This study examined the utility of Facebook advertisements to recruit smokers and heavy drinking smokers for treatment research and evaluated smoking and alcohol use and current treatment goals among those who responded to the Web-based survey. METHODS: Using Facebook's advertising program, 3 separate advertisements ran for 2 months targeting smokers who were thinking about quitting. Advertisements were shown to adult (at least 18 years of age), English-speaking Facebook users in the greater New Haven, Connecticut, area. Participants were invited to complete a Web based survey to determine initial eligibility for a smoking cessation research study. RESULTS: Advertisements generated 1781 clicks and 272 valid, completed surveys in 2 months, with one advertisement generating the most interest. Facebook advertising was highly cost-effective, averaging $0.27 per click, $1.76 per completed survey, and $4.37 per participant meeting initial screening eligibility. On average, those who completed the Web-based survey were 36.8 (SD 10.4) years old, and 65.8% (179/272) were female. Advertisements were successful in reaching smokers; all respondents reported daily smoking (mean 16.2 [SD 7.0] cigarettes per day). The majority of smokers (254/272, 93.4%) were interested in changing their smoking behavior immediately. Many smokers (161/272, 59.2%) also reported heavy alcohol consumption at least once a month. Among smokers interested in reducing their alcohol use, more were heavy drinkers (45/56, 80.4%) compared to non-heavy drinkers (11/56, 19.6%; chi(2)[1,N=272]=13.0, P<.001). Of those who met initial screening eligibility from the Web-based survey, 12.7% (14/110) attended an in-person follow-up appointment. CONCLUSIONS: Social media advertisements designed to target smokers were cost-effective and successful for reaching adult smokers interested in treatment. Additionally, recruiting for smokers reached those who also drink alcohol heavily, many of whom were interested in changing this behavior as well. However, additional social media strategies may be needed to engage individuals into treatment after completion of Web-based screening surveys. PMID- 27194459 TI - Acute side effects of three commonly used gadolinium contrast agents in the paediatric population. AB - OBJECTIVE: To determine the incidence of acute side effects of three commonly used gadolinium contrast agents in the paediatric population. METHODS: A retrospective review of medical records was performed to determine the incidence of acute adverse side effects of i.v. gadolinium contrast agents [MultiHance((r)) (Bracco Diagnostics Inc., Princeton, NJ), Magnevist((r)) (Bayer Healthcare Pharmaceuticals, Wayne, NJ) or Gadavist((r)) (Bayer HealthCare Pharmaceuticals)] in paediatric patients. RESULTS: 40 of the 2393 patients who received gadolinium contrast agents experienced acute side effects, representing an incidence of 1.7%. The majority of the acute side effects (in 30 patients) were nausea and vomiting. The incidence was significantly higher in non-sedated patients (2.37% vs 0.7%; p = 0.0018). Furthermore, without sedation, the incidence of both nausea and vomiting was significantly higher in children receiving MultiHance, with a 4.48% incidence of nausea when compared with Magnevist (0.33%, p < 0.0001) and Gadavist (0.28%, p < 0.0001) and a 2.36% incidence of vomiting compared with those for Magnevist (0.50%, p = 0.0054) and Gadavist (0.28%, p = 0.014), whereas no difference was observed between Magnevist and Gadavist within the power of the study. In addition, there was no apparent difference between any of the three contrast agents for the incidence of allergy or other acute side effects detected, given the sample size. CONCLUSION: The gadolinium contrast agents MultiHance, Magnevist and Gadavist have a low incidence of acute side effects in the paediatric population, a rate that is further reduced in moderately sedated patients. MultiHance demonstrated significantly increased incidence of gastrointestinal symptoms compared with Magnevist and Gadavist. ADVANCES IN KNOWLEDGE: The incidence of acute side effects of three commonly used gadolinium contrast agents was determined in the paediatric population, which can have clinical implications. PMID- 27194460 TI - Dilatation of the spinal epidural venous plexus in patients with prominent epidural fat. AB - OBJECTIVE: The purpose of this study was to evaluate the correlation between the dilatation of the spinal epidural venous plexus (SEVP) and the amount of epidural fat (EF). METHODS: Between January 2007 and January 2012, 116 patients with prominent EF and 116 control subjects without prominent EF were included in this study. On the lumbar MR images, we graded the amount of EF and counted the number of vertebrae to determine the longitudinal extent of the EF. We evaluated and classified the dilatation of the SEVP and the degree of central canal stenosis. RESULTS: SEVP dilatation significantly differed between the group with prominent EF and the control group (p-value < 0.0001). Dilatation of the anterior epidural veins was seen in all subjects with dilatation of the SEVP. In the group with prominent EF, 80 (69%) patients showed dilatation of the posterior epidural veins. The longitudinal extent of the prominent EF was significantly associated with the grade of SEVP dilatation. The EF grade and the sum of the EF grades of all levels of the lumbar spine with prominent EF showed a positive correlation with the grade of central canal stenosis (r = 0.421 and r = 0.347, respectively; p-value < 0.0001). CONCLUSION: The dilatation of epidural veins was statistically significant in patients with prominent EF. The detection of SEVP dilatation on MR images may be helpful for spine surgery involving the epidural space. ADVANCES IN KNOWLEDGE: Owing to the risk of bleeding, the detection of SEVP dilatation on MRI may be helpful when considering decompression surgery with a posterior approach for spinal stenosis caused by prominent EF. PMID- 27194458 TI - The potential of imaging techniques as a screening tool for colorectal cancer: a cost-effectiveness analysis. AB - OBJECTIVE: Imaging may be promising for colorectal cancer (CRC) screening, since it has test characteristics comparable with colonoscopy but is less invasive. We aimed to assess the potential of CT colonography (CTC) and MR colonography (MRC) in terms of (cost-effectiveness) using the Adenoma and Serrated pathway to Colorectal CAncer model. METHODS: We compared several CTC and MRC strategies with 5- or 10-yearly screening intervals with no screening, 10-yearly colonoscopy screening and biennial faecal immunochemical test (FIT) screening. We assumed trial-based participation rates in the base-case analyses and varied the rates in sensitivity analyses. Incremental lifetime costs and health effects were estimated from a healthcare perspective. RESULTS: The health gain of CTC and MRC was similar and ranged from 0.031 to 0.048 life-year gained compared with no screening, for 2-5 screening rounds. Lifetime costs per person for MRC strategies were ?60-110 higher than those for CTC strategies with an equal number of screening rounds. All imaging-based strategies were cost-effective compared with no screening. FIT screening was the dominant screening strategy, leading to most LYG and highest cost-savings. Compared with three rounds of colonoscopy screening, CTC with five rounds was found to be cost-effective in an incremental analysis of imaging strategies. Assumptions on screening participation have a major influence on the ordering of strategies in terms of costs and effects. CONCLUSION: CTC and MRC have potential for CRC screening, compared with no screening and compared with three rounds of 10-yearly colonoscopy screening. When taking FIT screening as the reference, imaging is not cost-effective. Participation is an important driver of effectiveness and cost estimates. ADVANCES IN KNOWLEDGE: This is the first study to assess the cost-effectiveness of MRC screening for CRC. PMID- 27194462 TI - A first report of hydroxylated apatite as structural biomineral in Loasaceae - plants' teeth against herbivores. AB - Biomineralization provides living organisms with various materials for the formation of resilient structures. Calcium phosphate is the main component of teeth and bones in vertebrates, whereas especially silica serves for the protection against herbivores on many plant surfaces. Functional calcium phosphate structures are well-known from the animal kingdom, but had not so far been reported from higher plants. Here, we document the occurrence of calcium phosphate biomineralization in the South-American plant group Loasaceae (rock nettle family), which have stinging trichomes similar to those of the well-known stinging nettles (Urtica). Stinging hairs and the smaller, glochidiate trichomes contained nanocrystalline hydroxylated apatite, especially in their distal portions, replacing the silica found in analogous structures of other flowering plants. This could be demonstrated by chemical, spectroscopic, and diffraction analyses. Some species of Loasaceae contained both calcium phosphate and silica in addition to calcium carbonate. The intriguing discovery of structural hydroxylated apatite in plants invites further studies, e.g., on its systematic distribution across the family, the genetic and cellular control of plant biomineralization, the properties and ultrastructure of calcium phosphate. It may prove the starting point for the development of biomimetic calcium phosphate composites based on a cellulose matrix. PMID- 27194463 TI - Using depletion to control colloidal crystal assemblies of hard cuboctahedra. AB - Depletion interactions arise from entropic forces, and their ability to induce aggregation and even ordering of colloidal particles through self-assembly is well established, especially for spherical colloids. We vary the size and concentration of penetrable hard sphere depletants in a system of cuboctahedra, and we show how depletion changes the preferential facet alignment of the colloids and thereby selects different crystal structures. Moreover, we explain the cuboctahedra phase behavior using perturbative free energy calculations. We find that cuboctahedra can form a stable simple cubic phase, and, remarkably, that the stability of this phase can be rationalized only by considering the effects of both the colloid and depletant entropy. We corroborate our results by analyzing how the depletant concentration and size affect the emergent directional entropic forces and hence the effective particle shape. We propose the use of depletants as a means of easily changing the effective shape of self assembling anisotropic colloids. PMID- 27194461 TI - Vascular-targeted nanocarriers: design considerations and strategies for successful treatment of atherosclerosis and other vascular diseases. AB - Vascular-targeted nanocarriers are an attractive option for the treatment of a number of cardiovascular diseases, as they allow for more specific delivery and increased efficacy of many small molecule drugs. However, immune clearance, limited cellular uptake, and particle-cell dynamics in blood flow can hinder nanocarrier efficacy in many applications. This review aims to investigate successful strategies for the use of vascular-targeted nanocarriers in the treatment of cardiovascular diseases such as atherosclerosis. In particular, the review will highlight strategies employed for actively targeting the components of the atherosclerotic plaque, including endothelial cells, macrophages, and platelets and passive targeting via endothelial permeability, as well as design specifications (such as size, shape, and density) aimed at enhancing the ability of nanocarriers to reach the vascular wall. WIREs Nanomed Nanobiotechnol 2016, 8:909-926. doi: 10.1002/wnan.1414 For further resources related to this article, please visit the WIREs website. PMID- 27194464 TI - Hematopoietic stem cell transplantation for people with sickle cell disease. AB - BACKGROUND: Sickle cell disease is a genetic disorder involving a defect in the red blood cells due to its sickled hemoglobin. The main therapeutic interventions include preventive and supportive measures. Hematopoietic stem cell transplantations are carried out with the aim of replacing the defective cells and their progenitors (hematopoietic (i.e. blood forming) stem cells) in order to correct the disorder. This is an update of a previously published review. OBJECTIVES: To determine whether stem cell transplantation can improve survival and prevent symptoms and complications associated with sickle cell disease. To examine the risks of stem cell transplantation against the potential long-term gain for people with sickle cell disease. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Group's Haemoglobinopathies Trials Register complied from electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (updated each new issue of The Cochrane Library) and quarterly searches of MEDLINE.Unpublished work was identified by searching the abstract books of major conference proceedings and we conducted a search of the website: www.ClinicalTrials.gov.Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 06 October 2015. SELECTION CRITERIA: Randomized controlled and quasi-randomized studies that compared any method of stem cell transplantation with either each other or with any of the preventive or supportive interventions (e.g. periodic blood transfusion, use of hydroxyurea, antibiotics, pain relievers, supplemental oxygen) in people with sickle cell disease irrespective of the type of sickle cell disease, gender and setting. DATA COLLECTION AND ANALYSIS: No relevant trials were identified. MAIN RESULTS: Ten trials were identified by the initial search and none for the update. None of these trials were suitable for inclusion in this review. AUTHORS' CONCLUSIONS: Reports on the use of hematopoietic stem cell transplantation improving survival and preventing symptoms and complications associated with sickle cell disease are currently limited to observational and other less robust studies. No randomized controlled trial assessing the benefit or risk of hematopoietic stem cell transplantations was found. Thus, this systematic review identifies the need for a multicentre randomized controlled trial assessing the benefits and possible risks of hematopoietic stem cell transplantations comparing sickle status and severity of disease in people with sickle cell disease. PMID- 27194465 TI - Higher Hemoglobin A1c After Discharge Is an Independent Predictor of Adverse Outcomes in Patients With Acute Coronary Syndrome - Findings From the PACIFIC Registry. AB - BACKGROUND: Optimal medical therapy (OMT) and the management of coronary risk factors are necessary for secondary prevention of major adverse cardiac and cerebrovascular events (MACCE) in post-acute coronary syndrome (ACS) patients. However, the effect of post-discharge patient adherence has not been investigated in Japanese patients. METHODS AND RESULTS: The Prevention of AtherothrombotiC Incidents Following Ischemic Coronary Attack (PACIFIC) registry was a multicenter, prospective observational study of 3,597 patients with ACS. Death or MACCE occurred in 229 patients between hospitalization and up to 1 year after discharge. Among 2,587 patients, the association between OMT adherence and risk factor control at 1 year and MACCE occurring between 1 and 2 years after discharge was assessed. OMT was defined as the use of antiplatelet agents, angiotensin-converting enzyme inhibitors, beta-blockers, and statins. Risk factor targets were: low-density lipoprotein-cholesterol <100 mg/dl, HbA1c <7.0%, non smoking status, blood pressure <130/80 mmHg, and 18.5<=body mass index<=24.9 kg/m(2). The incidence of MACCE was 1.8% and associated with female sex (P=0.020), age >=75 years (P=0.004), HbA1c >=7.0% (P=0.004), LV ejection fraction <35% (P<0.001), estimated glomerular filtration rate <60 ml/min (P=0.008), and history of cerebral infarction (P=0.003). In multivariate analysis, lower post discharge HbA1c was strongly associated with a lower risk of MACCE after ACS (P=0.004). CONCLUSIONS: Hyperglycemia after discharge is a crucial target for the prevention of MACCE in post-ACS patients. (Circ J 2016; 80: 1607-1614). PMID- 27194466 TI - Impact of Age on the Functional Significance of Intermediate Epicardial Artery Disease. AB - BACKGROUND: The functional significance of an intermediate coronary lesion is crucial for determining the treatment strategy, but age-related changes in cardiovascular function could affect the functional significance of an epicardial stenosis. The aim of this study was therefore to investigate the impact of age on fractional flow reserve (FFR) measurements in patients with intermediate coronary artery disease (CAD). METHODS AND RESULTS: Intracoronary pressure measurements and intravascular ultrasound (IVUS) were performed in 178 left anterior descending coronary arteries with intermediate stenosis. The morphological characteristics and FFR of 91 lesions in patients <65 years old were compared with those of 87 patients >=65 years old. There was no difference in lesion location, diameter stenosis, minimum lumen area, plaque burden, or lesion length between the 2 age groups. Elderly patients had higher FFR (0.81+/-0.06 vs. 0.79+/ 0.06, P=0.004) and lower ?FFR, defined as the difference between resting Pd/Pa and FFR (0.13+/-0.05 vs. 0.15+/-0.05, P=0.014). Age, along with the location and degree of stenosis, was independently associated with FFR and ?FFR (beta=0.162, P=0.008; beta=-0.131, P=0.043, respectively). CONCLUSIONS: Elderly patients with intermediate CAD are more likely to have higher FFR and lower ?FFR, despite a similar degree of epicardial stenosis, compared with younger patients. (Circ J 2016; 80: 1583-1589). PMID- 27194467 TI - Prognostic Significance of Insomnia in Heart Failure. AB - BACKGROUND: Insomnia is associated with incident heart failure (HF), but the clinical significance and impact of insomnia on HF remain unclear. METHODS AND RESULTS: Consecutive 1,011 patients admitted for HF were divided into 2 groups according to the presence of insomnia: HF with insomnia (insomnia group, n=519) and HF without insomnia (non-insomnia group, n=492). We compared (1) cardiac event rates including cardiac death and worsening HF; and (2) underlying clinical background including laboratory data, echocardiographic data, and cardiopulmonary exercise test between the 2 groups. On Kaplan-Meier analysis, cardiac event rate was significantly higher in the insomnia group than in the non-insomnia group (39.1 vs. 23.4%, P<0.001). The insomnia group, as compared with the non-insomnia group, had (1) higher plasma renin activity (P=0.042), renin concentration (P=0.007), and aldosterone (P=0.047); (2) lower peak VO2(14.9 vs. 16.3 ml/kg/min, P=0.002) and higher VE/VCO2slope (36.0 vs. 33.5, P=0.001); and (3) similar B-type natriuretic peptide and left ventricular ejection fraction. Importantly, on multivariate Cox proportional hazard analysis after adjusting for potential confounding factors, insomnia was an independent predictor of cardiac events in HF patients (hazard ratio, 1.899; P<0.001). CONCLUSIONS: Insomnia is an independent predictor of cardiac events in HF patients. HF patients with insomnia have activated renin-angiotensin-aldosterone system and lower exercise capacity. (Circ J 2016; 80: 1571-1577). PMID- 27194468 TI - Increased Coronary Perivascular Adipose Tissue Volume in Patients With Vasospastic Angina. AB - BACKGROUND: Recent studies have suggested that coronary perivascular adipose tissue (PVAT) impairs coronary vasomotion, so we examined whether PVAT is increased at the spastic coronary segment in patients with vasospastic angina (VSA). METHODS AND RESULTS: PVAT volume in the left anterior descending (LAD) coronary arteries on CT coronary angiography was significantly increased in 48 VSA patients with LAD spasm compared with 18 controls (30.7+/-2.0 vs. 21.0+/-3.2 cm(3), P=0.01), whereas that of total epicardial adipose tissue was comparable between the 2 groups. CONCLUSIONS: The results suggested an important role of PVAT in the pathogenesis of coronary spasm. (Circ J 2016; 80: 1653-1656). PMID- 27194469 TI - Characteristics and Outcomes of Bath-Related Out-of-Hospital Cardiac Arrest in Japan. AB - BACKGROUND: Characteristics and outcomes of emergency patients with bath-related sudden cardiac arrest in prehospital settings have not been sufficiently investigated. METHODS AND RESULTS: From a prospective population-based registry, which covers all out-of-hospital cardiac arrests (OHCAs) in Osaka City, a total of 642 patients who had a bath-related OHCA from 2012 to 2014 were enrolled in the analyses. The characteristics and outcomes of OHCA were compared by three locations of arrest: home baths (n=512), public baths (n=102), and baths in other public institutions (n=28). Overall, bath-related OHCAs mainly occurred in winter (December-February, 48.9%, 314/642). The proportion of OHCAs that were witnessed by bystanders was 6.4% (33/512) in home baths, 17.6% (18/102) in public baths, and 25.0% (7/28) in baths in other public institutions. The proportion of public access automated external defibrillator pad application was 0.8% (4/512) in home baths, 6.9% (7/102) in public baths, and 50.0% (14/28) in baths in other public institutions. Only 1 survivor with a favorable neurologic outcome was observed in a home bath, whereas there were no patients who survived with favorable neurologic outcomes in public baths and baths in other public institutions. CONCLUSIONS: Bath-related OHCAs mainly occurred in winter, and the outcome of victims was exceedingly poor, irrespective of location of arrest. The establishment of preventive measures as well as earlier recognition of cardiac arrest by bystanders are needed. (Circ J 2016; 80: 1564-1570). PMID- 27194470 TI - Shining the Light on Calcium in the Catheterization Lab. PMID- 27194471 TI - Inhibition of the hexosamine biosynthetic pathway promotes castration-resistant prostate cancer. AB - The precise molecular alterations driving castration-resistant prostate cancer (CRPC) are not clearly understood. Using a novel network-based integrative approach, here, we show distinct alterations in the hexosamine biosynthetic pathway (HBP) to be critical for CRPC. Expression of HBP enzyme glucosamine phosphate N-acetyltransferase 1 (GNPNAT1) is found to be significantly decreased in CRPC compared with localized prostate cancer (PCa). Genetic loss-of-function of GNPNAT1 in CRPC-like cells increases proliferation and aggressiveness, in vitro and in vivo. This is mediated by either activation of the PI3K-AKT pathway in cells expressing full-length androgen receptor (AR) or by specific protein 1 (SP1)-regulated expression of carbohydrate response element-binding protein (ChREBP) in cells containing AR-V7 variant. Strikingly, addition of the HBP metabolite UDP-N-acetylglucosamine (UDP-GlcNAc) to CRPC-like cells significantly decreases cell proliferation, both in-vitro and in animal studies, while also demonstrates additive efficacy when combined with enzalutamide in-vitro. These observations demonstrate the therapeutic value of targeting HBP in CRPC. PMID- 27194474 TI - Liposome production by microfluidics: potential and limiting factors. AB - This paper provides an analysis of microfluidic techniques for the production of nanoscale lipid-based vesicular systems. In particular we focus on the key issues associated with the microfluidic production of liposomes. These include, but are not limited to, the role of lipid formulation, lipid concentration, residual amount of solvent, production method (including microchannel architecture), and drug loading in determining liposome characteristics. Furthermore, we propose microfluidic architectures for the mass production of liposomes with a view to potential industrial translation of this technology. PMID- 27194472 TI - Sodium tanshinone IIA sulfonate inhibits hypoxia-induced enhancement of SOCE in pulmonary arterial smooth muscle cells via the PKG-PPAR-gamma signaling axis. AB - Our laboratory previously showed that sodium tanshinone IIA sulfonate (STS) inhibited store-operated Ca(2+) entry (SOCE) through store-operated Ca(2+) channels (SOCC) via downregulating the expression of transient receptor potential canonical proteins (TRPC), which contribute to the formation of SOCC (Wang J, Jiang Q, Wan L, Yang K, Zhang Y, Chen Y, Wang E, Lai N, Zhao L, Jiang H, Sun Y, Zhong N, Ran P, Lu W. Am J Respir Cell Mol Biol 48: 125-134, 2013). The detailed molecular mechanisms by which STS inhibits SOCE and downregulates TRPC, however, remain largely unknown. We have previously shown that, under hypoxic conditions, inhibition of protein kinase G (PKG) and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) signaling axis results in the upregulation of TRPC (Wang J, Yang K, Xu L, Zhang Y, Lai N, Jiang H, Zhang Y, Zhong N, Ran P, Lu W. Am J Respir Cell Mol Biol 49: 231-240, 2013). This suggests that strategies targeting the restoration of this signaling pathway may be an effective treatment strategy for pulmonary hypertension. In this study, our results demonstrated that STS treatment can effectively prevent the hypoxia-mediated inhibition of the PKG PPAR-gamma signaling axis in rat distal pulmonary arterial smooth muscle cells (PASMCs) and distal pulmonary arteries. These effects of STS treatment were blocked by pharmacological inhibition or specific small interfering RNA knockdown of either PKG or PPAR-gamma. Moreover, targeted PPAR-gamma agonist markedly enhanced the beneficial effects of STS. These results comprehensively suggest that STS treatment can prevent hypoxia-mediated increases in intracellular calcium homeostasis and cell proliferation, by targeting and restoring the hypoxia-inhibited PKG-PPAR-gamma signaling pathway in PASMCs. PMID- 27194473 TI - Regulation of membrane KCNQ1/KCNE1 channel density by sphingomyelin synthase 1. AB - Sphingomyelin synthase (SMS) catalyzes the conversion of phosphatidylcholine and ceramide to sphingomyelin and diacylglycerol. We previously showed that SMS1 deficiency leads to a reduction in expression of the K(+) channel KCNQ1 in the inner ear (Lu MH, Takemoto M, Watanabe K, Luo H, Nishimura M, Yano M, Tomimoto H, Okazaki T, Oike Y, and Song WJ. J Physiol 590: 4029-4044, 2012), causing hearing loss. However, it remains unknown whether this change in expression is attributable to a cellular process or a systemic effect in the knockout animal. Here, we examined whether manipulation of SMS1 activity affects KCNQ1/KCNE1 currents in individual cells. To this end, we expressed the KCNQ1/KCNE1 channel in human embryonic kidney 293T cells and evaluated the effect of SMS1 manipulations on the channel using whole cell recording. Application of tricyclodecan-9-yl-xanthogenate, a nonspecific inhibitor of SMSs, significantly reduced current density and altered channel voltage dependence. Knockdown of SMS1 by a short hairpin RNA, however, reduced current density alone. Consistent with this, overexpression of SMS1 increased the current density without changing channel properties. Furthermore, application of protein kinase D inhibitors also suppressed current density without changing channel properties; this effect was nonadditive with that of SMS1 short hairpin RNA. These results suggest that SMS1 positively regulates KCNQ1/KCNE1 channel density in a protein kinase D-dependent manner. PMID- 27194475 TI - Densely charged polyelectrolyte-stuffed nanochannel arrays for power generation from salinity gradient. AB - We devised anodized aluminium oxide (AAO) frame-supported polyelectrolytic ion exchange membranes for the application of electrical power generation systems where salinity differences are present. A series of polyelectrolytic AAO membranes (PAMs) were fabricated as a function of concentration of monomers and cross-linkers. Of the ion-selective PAMs as made, the membranes from the most concentrated monomers and cross-linkers, C-PAM100 and A-PAM100, showed the highest area resistances and permselectivities (the resistances were 4.9 and 2.9 Omega . cm(2), the permseletivities for C-PAM100 and A-PAM100 were 99 and 89%, respectively). The measured resistances and permselectivities allowed the power density to be estimated for C-PAM100 and A-PAM100, 3.5 W/m(2), and experimentally obtained power density using a reverse electrodialysis (RED) stack was 17.3 mW/m(2). In addition, we investigated the influence of an AAO framework on a membrane resistance by comparing the PAMs with polyelectrolyte-stuffed capillaries, revealing that the resistance of the PAM has plenty of potential to be further reduced by optimizing the AAO pore spaces. PMID- 27194478 TI - Examining the Uptake of Central Nervous System Drugs and Candidates across the Blood-Brain Barrier. AB - Assessing the equilibration of the unbound drug concentrations across the blood brain barrier (Kp,uu) has progressively replaced the partition coefficient based on the ratio of the total concentration in brain tissue to blood (Kp). Here, in vivo brain distribution studies were performed on a set of central nervous system (CNS)-targeted compounds in both rats and P-glycoprotein (P-gp) genetic knockout mice. Several CNS drugs are characterized by Kp,uu values greater than unity, inferring facilitated uptake across the rodent blood-brain barrier (BBB). Examples are shown in which Kp,uu also increases above unity on knockout of P-gp, highlighting the composite nature of this parameter with respect to facilitated BBB uptake, efflux, and passive diffusion. Several molecules with high Kp,uu values share common structural elements, whereas uptake across the BBB appears more prevalent in the CNS-targeted drug set than the chemical templates being generated within the current lead optimization paradigm. Challenges for identifying high Kp,uu compounds are discussed in the context of acute versus steady-state data and cross-species differences. Evidently, there is a need for better predictive models of human brain Kp,uu. PMID- 27194477 TI - Functional Selectivity of CB2 Cannabinoid Receptor Ligands at a Canonical and Noncanonical Pathway. AB - The CB2 cannabinoid receptor (CB2) remains a tantalizing, but unrealized therapeutic target. CB2 receptor ligands belong to varied structural classes and display extreme functional selectivity. Here, we have screened diverse CB2 receptor ligands at canonical (inhibition of adenylyl cyclase) and noncanonical (arrestin recruitment) pathways. The nonclassic cannabinoid (-)-cis-3-[2-hydroxy 4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol (CP55940) was the most potent agonist for both pathways, while the classic cannabinoid ligand (6aR,10aR)-3-(1,1-Dimethylbutyl)-6a,7,10,10a-tetrahydro-6,6,9-trimethyl-6H dibenzo[b,d]pyran JWH133) was the most efficacious agonist among all the ligands profiled in cyclase assays. In the cyclase assay, other classic cannabinoids showed little [(-)-trans-Delta(9)-tetrahydrocannabinol and (-)-(6aR,7,10,10aR) tetrahydro-6,6,9-trimethyl-3-(1-methyl-1-phenylethyl)-6H-dibenzo[b,d]pyran-1-ol] (KM233) to no efficacy [(6aR,10aR)-1-methoxy-6,6,9-trimethyl-3-(2-methyloctan-2 yl)-6a,7,10,10a-tetrahydrobenzo[c]chromene(L759633) and (6aR,10aR)-3-(1,1 dimethylheptyl)-6a,7,8,9,10,10a-hexahydro-1-methoxy-6,6-dimethyl-9-methylene-6H dibenzo[b,d]pyran]L759656. Most aminoalkylindoles, including [(3R)-2,3-dihydro-5 methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1 naphthalenyl-methanone, monomethanesulfonate (WIN55212-2), were moderate efficacy agonists. The cannabilactone 3-(1,1-dimethyl-heptyl)-1-hydroxy-9-methoxy benzo(c)chromen-6-one (AM1710) was equiefficacious to CP55940 to inhibit adenylyl cyclase, albeit with lower potency. In the arrestin recruitment assays, all classic cannabinoid ligands failed to recruit arrestins, indicating a bias toward G-protein coupling for this class of compound. All aminoalkylindoles tested, except for WIN55212-2 and (1-pentyl-1H-indol-3-yl)(2,2,3,3 tetramethylcyclopropyl)-methanone (UR144), failed to recruit arrestin. WIN55212-2 was a low efficacy agonist for arrestin recruitment, while UR144 was arrestin biased with no significant inhibition of cyclase. Endocannabinoids were G-protein biased with no arrestin recruitment. The diarylpyrazole antagonist 5-(4-chloro-3 methylphenyl)-1-[(4-methylphenyl)methyl]-N-[(1S,2S,4R)-1,3,3 trimethylbicyclo[2.2.1]hept-2-yl]-1H-pyrazole-3-carboxamide (SR144258) was an inverse agonist in cyclase and arrestin recruitment assays while the aminoalkylindole 6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4 methoxyphenyl)methanone (AM630) and carboxamide N-(1,3-benzodioxol-5-ylmethyl) 1,2-dihydro-7-methoxy-2-oxo-8-(pentyloxy)-3-quinolinecarboxamide (JTE907) were inverse agonists in cyclase but low efficacy agonists in arrestin recruitment assays. Thus, CB2 receptor ligands display strong and varied functional selectivity at both pathways. Therefore, extreme care must be exercised when using these compounds to infer the role of CB2 receptors in vivo. PMID- 27194479 TI - Treatment with Adenosine Receptor Agonist Ameliorates Pain Induced by Acute and Chronic Inflammation. AB - Rheumatoid arthritis is an inflammatory autoimmune condition, and tumor necrosis factor-alpha (TNF-alpha) plays an important role in its pathophysiology. In vitro, (E)-N'-(3,4-dimethoxybenzylidene)-N-methylbenzohydrazide (LASSBio-1359) has exhibited anti-TNF-alpha properties, and in vivo these effects are mediated via activation of adenosine receptor. This work investigates the antinociceptive action of LASSBio-1359 in murine models of acute and chronic inflammatory pain. Male mice received an intraperitoneal injection of LASSBio-1359 and then were evaluated in formalin- and carrageenan-induced paw edema assays. Complete Freund's adjuvant (CFA) was used to induce a mouse model of monoarthritis. These mice were treated with LASSBio-1359 by oral gavage to evaluate thermal and mechanical hyperalgesia. TNF-alpha and inducible nitric oxide synthase (iNOS) expression as well as histologic features were analyzed. The time of reactivity to formalin in the neurogenic phase was reduced from 56.3 +/- 6.0 seconds to 32.7 +/- 2.2 seconds and 23.8 +/- 2.6 seconds after treatment with LASSBio-1359 at doses of 10 mg/kg and 20 mg/kg, respectively. A reversal of the antinociceptive action of LASSBio-1359 was observed in the inflammatory phase after treatment with ZM 241385 [4-(2-[7-amino-2-(2-furly)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5 ylamino]ethyl)phenol], an adenosine A2A antagonist. Carrageenan-induced thermal and mechanical hyperalgesia were reduced after treatment with LASSBio-1359. Similarly, CFA-induced thermal and mechanical hyperalgesia were reduced after treatment with LASSBio-1359 (25 and 50 mg/kg). Levels of TNF-alpha and iNOS expression increased in the monoarthritis model and were normalized in animals treated with LASSBio-1359, which was also associated with beneficial effects in the histologic analysis. These results suggest that LASSBio-1359 represents an alternative treatment of monoarthritis. PMID- 27194480 TI - The Role of Program-Supported Mentoring Relationships in Promoting Youth Mental Health, Behavioral and Developmental Outcomes. AB - This study examined the relationship between youth mentoring status and behavioral, developmental, and emotional outcomes for 859 youths aged 6-17 participating in a national survey of Big Brothers Big Sisters community mentoring relationships (MRs). Youth self-reported behaviors and mental health occurred at the baseline assessment (before being paired to a mentor) and at 18 months follow-up. Youth mentoring status was categorized as follows: (1) continuous MR less than 12 months (n = 131); (2) continuous MR 12 or more months (n = 253); (3) dissolved MR less than 12 months (n = 110); (4) dissolved MR 12 or more months (n = 70); 5) MR with a second mentor (re-matched; n = 83); and (6); never mentored (n = 212). Structural equation model results at 18 months revealed that mentored youths, especially those in MR lasting 12 or more months (continuous or dissolved), reported significantly fewer behavioral problems and fewer symptoms of depression and social anxiety than did non-mentored youths. They also reported stronger coping skills and emotional support from parents. Mentored girls and boys in long-term relationships experienced positive outcomes. Re-matched girls displayed better outcomes than did never-mentored girls while there was some evidence of harmful outcomes for re-matched boys. Threats to internal validity are examined including the possibility of pre-existing baseline differences between mentored and non-mentored youths. Implications for mentoring programs are discussed. PMID- 27194481 TI - Model inversion via multi-fidelity Bayesian optimization: a new paradigm for parameter estimation in haemodynamics, and beyond. AB - We present a computational framework for model inversion based on multi-fidelity information fusion and Bayesian optimization. The proposed methodology targets the accurate construction of response surfaces in parameter space, and the efficient pursuit to identify global optima while keeping the number of expensive function evaluations at a minimum. We train families of correlated surrogates on available data using Gaussian processes and auto-regressive stochastic schemes, and exploit the resulting predictive posterior distributions within a Bayesian optimization setting. This enables a smart adaptive sampling procedure that uses the predictive posterior variance to balance the exploration versus exploitation trade-off, and is a key enabler for practical computations under limited budgets. The effectiveness of the proposed framework is tested on three parameter estimation problems. The first two involve the calibration of outflow boundary conditions of blood flow simulations in arterial bifurcations using multi fidelity realizations of one- and three-dimensional models, whereas the last one aims to identify the forcing term that generated a particular solution to an elliptic partial differential equation. PMID- 27194476 TI - Evaluating cell reprogramming, differentiation and conversion technologies in neuroscience. AB - The scarcity of live human brain cells for experimental access has for a long time limited our ability to study complex human neurological disorders and elucidate basic neuroscientific mechanisms. A decade ago, the development of methods to reprogramme somatic human cells into induced pluripotent stem cells enabled the in vitro generation of a wide range of neural cells from virtually any human individual. The growth of methods to generate more robust and defined neural cell types through reprogramming and direct conversion into induced neurons has led to the establishment of various human reprogramming-based neural disease models. PMID- 27194482 TI - The social brain: scale-invariant layering of Erdos-Renyi networks in small-scale human societies. AB - The cognitive ability to form social links that can bind individuals together into large cooperative groups for safety and resource sharing was a key development in human evolutionary and social history. The 'social brain hypothesis' argues that the size of these social groups is based on a neurologically constrained capacity for maintaining long-term stable relationships. No model to date has been able to combine a specific socio cognitive mechanism with the discrete scale invariance observed in ethnographic studies. We show that these properties result in nested layers of self-organizing Erdos-Renyi networks formed by each individual's ability to maintain only a small number of social links. Each set of links plays a specific role in the formation of different social groups. The scale invariance in our model is distinct from previous 'scale-free networks' studied using much larger social groups; here, the scale invariance is in the relationship between group sizes, rather than in the link degree distribution. We also compare our model with a dominance-based hierarchy and conclude that humans were probably egalitarian in hunter-gatherer like societies, maintaining an average maximum of four or five social links connecting all members in a largest social network of around 132 people. PMID- 27194485 TI - Structural analysis of oncogenic mutation of isocitrate dehydrogenase 1. AB - Arginine to histidine mutation at position 132 (R132H) in isocitrate dehydrogenase 1 (IDH1) led to reduced affinity of the respective enzymes for isocitrate and increased affinity for alpha-ketoglutarate (AKG) and NADPH. This phenomenon retarded oxidative decarboxylation of isocitrate to AKG and conferred a novel enzymatic activity that facilitated the reduction of AKG to d-2 hydroxyglutarate (d-2HG). The loss of isocitrate utilization and gain of 2HG production from IDH1 R132H had been taken up as a fundamental problem and to solve this, structural biology approaches were adopted. Interaction analysis was carried out to investigate the IDH1 substrate binding environment. The altered behaviour of mutant and native IDH1 in interaction analysis was explored by performing long-term molecular dynamics simulations (~300 ns). This study reports a comprehensive atomic behaviour of the gain-of-function mutation (R132H) in the IDH1 enzyme which in turn provides a direction towards new therapeutics. PMID- 27194483 TI - Distinct properties of semiquinone species detected at the ubiquinol oxidation Qo site of cytochrome bc1 and their mechanistic implications. AB - The two-electron ubiquinol oxidation or ubiquinone reduction typically involves semiquinone (SQ) intermediates. Natural engineering of ubiquinone binding sites of bioenergetic enzymes secures that SQ is sufficiently stabilized, so that it does not leave the site to membranous environment before full oxidation/reduction is completed. The ubiquinol oxidation Qo site of cytochrome bc1 (mitochondrial complex III, cytochrome b6f in plants) has been considered an exception with catalytic reactions assumed to involve highly unstable SQ or not to involve any SQ intermediate. This view seemed consistent with long-standing difficulty in detecting any reaction intermediates at the Qo site. New perspective on this issue is now offered by recent, independent reports on detection of SQ in this site. Each of the described SQs seems to have different spectroscopic properties leaving space for various interpretations and mechanistic considerations. Here, we comparatively reflect on those properties and their consequences on the SQ stabilization, the involvement of SQ in catalytic reactions, including proton transfers, and the reactivity of SQ with oxygen associated with superoxide generation activity of the Qo site. PMID- 27194486 TI - First-principles computation of surface segregation in L10 CoPt magnetic nanoparticles. AB - In this study, we have employed the first-principles density functional theory (DFT) computational method to predict the influence of surface segregation on the magnetic properties of small L10 CoPt nanoparticles. For both the modelled cuboidal (with a chemical formula of Co26Pt12) and cuboctahedral (with a chemical formula of Co18Pt20) CoPt nanoparticles, the DFT calculations predict that Pt surface segregation should occur thermodynamically. Associated with this Pt surface segregation, the surface-segregated CoPt magnetic nanoparticles are predicted to have significantly reduced magnetic moments and magnetic anisotropy energies than those of the corresponding bulk-terminated (i.e. non-segregated) nanoparticles. Hence, our study suggests that surface segregation could deteriorate the magnetic properties of CoPt nanoparticles. PMID- 27194484 TI - Gradual conversion of cellular stress patterns into pre-stressed matrix architecture during in vitro tissue growth. AB - The complex arrangement of the extracellular matrix (ECM) produced by cells during tissue growth, healing and remodelling is fundamental to tissue function. In connective tissues, it is still unclear how both cells and the ECM become and remain organized over length scales much larger than the distance between neighbouring cells. While cytoskeletal forces are essential for assembly and organization of the early ECM, how these processes lead to a highly organized ECM in tissues such as osteoid is not clear. To clarify the role of cellular tension for the development of these ordered fibril architectures, we used an in vitro model system, where pre-osteoblastic cells produced ECM-rich tissue inside channels with millimetre-sized triangular cross sections in ceramic scaffolds. Our results suggest a mechanical handshake between actively contracting cells and ECM fibrils: the build-up of a long-range organization of cells and the ECM enables a gradual conversion of cell-generated tension to pre-straining the ECM fibrils, which reduces the work cells have to generate to keep mature tissue under tension. PMID- 27194487 TI - Telemedicine for the acute management of stroke in Burgundy, France: an evaluation of effectiveness and safety. AB - BACKGROUND: In the context of the development of telemedicine in France to address low thrombolysis rates and limited stroke infrastructures, a star-shaped telestroke network was implemented in Burgundy (1.6 million inhabitants). We evaluated the safety and effectiveness of this network for thrombolysis in acute ischemic stroke patients. METHODS: One hundred and thirty-two consecutive patients who received intravenous thrombolysis during a telemedicine procedure (2012-2014) and 222 consecutive patients who were treated at the stroke center of Dijon University Hospital, France (2011-2012) were included. Main outcomes were the modified Rankin scale (mRS) score and case fatality at 3 months. Comparisons between groups were made using multivariable ordinal logistic regression and logistic regression analyses, respectively. RESULTS: Baseline characteristics of telethrombolysis patients were similar to those of patients undergoing thrombolysis locally except for a higher frequency of previous cancer and pre morbid handicap, and a trend towards greater severity at admission in the former. The distribution of mRS scores at 3 months was similar between groups, as were case-fatality rates (18.9% in the telethrombolysis group versus 16.5%, P = 0.56). In multivariable models, telethrombolysis did not independently influence functional outcomes at 3 months (odds ratio for a shift towards a worse outcome on the mRS, 1.11; 95% confidence interval, 0.74-1.66, P = 0.62) or death (odds ratio, 0.86; 95% confidence interval, 0.44-1.69, P = 0.66). CONCLUSION: The implementation of a regional telemedicine network for the management of acute ischemic stroke appeared to be effective and safe. Thanks to this network, the proportion of patients who benefit from thrombolysis will increase. Further research is needed to evaluate economic benefits. PMID- 27194488 TI - Gastrointestinal and liver disease in Adult Life After Childhood Cancer in Scandinavia: A population-based cohort study. AB - Survival after childhood cancer diagnosis has remarkably improved, but emerging evidence suggests that cancer-directed therapy may have adverse gastrointestinal late effects. We aimed to comprehensively assess the frequency of gastrointestinal and liver late effects among childhood cancer survivors and compare this frequency with the general population. Our population-based cohort study included all 1-year survivors of childhood and adolescent cancer in Denmark, Finland, Iceland, Norway and Sweden diagnosed from the 1940s and 1950s. Our outcomes of interest were hospitalization rates for gastrointestinal and liver diseases, which were ascertained from national patient registries. We calculated standardized hospitalization rate ratios (RRs) and absolute excess rates comparing hospitalizations of any gastrointestinal or liver disease and for specific disease entities between survivors and the general population. The study included 31,132 survivors and 207,041 comparison subjects. The median follow-up in the hospital registries were 10 years (range: 0-42) with 23% of the survivors being followed at least to the age of 40 years. Overall, survivors had a 60% relative excess of gastrointestinal or liver diseases [RR: 1.6, 95% confidence interval (CI): 1.6-1.7], which corresponds to an absolute excess of 360 (95% CI: 330-390) hospitalizations per 100,000 person-years. Survivors of hepatic tumors, neuroblastoma and leukemia had the highest excess of gastrointestinal and liver diseases. In addition, we observed a relative excess of several specific diseases such as esophageal stricture (RR: 13; 95% CI: 9.2-20) and liver cirrhosis (RR: 2.9; 95% CI: 2.0-4.1). Our findings provide useful information about the breadth and magnitude of late complications among childhood cancer survivors and can be used for generating hypotheses about potential exposures related to these gastrointestinal and liver late effects. PMID- 27194489 TI - Outcomes for Hip Arthroscopy According to Sex and Age: A Comparative Matched Group Analysis. AB - BACKGROUND: Factors such as age and sex are postulated to play a role in outcomes following arthroscopy for femoroacetabular impingement; however, to our knowledge, no data currently delineate outcomes on the basis of these factors. The purpose of this study was to compare clinical outcomes of patients undergoing hip arthroscopy for femoroacetabular impingement according to sex and age. METHODS: One hundred and fifty patients undergoing hip arthroscopy for femoroacetabular impingement by a single fellowship-trained surgeon were prospectively analyzed, with 25 patients in each of the following groups: female patients younger than 30 years of age, female patients 30 to 45 years of age, female patients older than 45 years of age, male patients younger than 30 years of age, male patients 30 to 45 years of age, and male patients older than 45 years of age. The primary outcomes included the Hip Outcome Score Activities of Daily Living Subscale (HOS-ADL), Hip Outcome Score Sport-Specific Subscale (HOS Sport), the modified Harris hip score (mHHS), and clinical improvement at the time of follow-up. RESULTS: At a minimum 2-year follow-up, all groups demonstrated significant improvements in the HOS-ADL, the HOS-Sport, and the mHHS (p < 0.0001). Female patients older than 45 years of age scored significantly worse on the HOS-ADL, HOS-Sport, and mHHS compared with female patients younger than 30 years of age (p < 0.0001 for all) and female patients 30 to 45 years of age (p < 0.017 for all). Male patients older than 45 years of age scored significantly worse on all outcomes compared with male patients younger than 30 years of age (p <= 0.011 for all) and male patients 30 to 45 years of age (p <= 0.021 for all). Incorporating both sexes, patients older than 45 years of age scored significantly worse on all outcomes compared with patients younger than 30 years of age (p < 0.0001 for all) and patients 30 to 45 years of age (p <= 0.001 for all). Female patients older than 45 years of age had significantly reduced radiographic preoperative joint space width compared with the two other female groups and the male groups who were 45 years of age or younger (p < 0.05 for all). CONCLUSIONS: Although all patients had significant improvements in all outcomes following hip arthroscopy, patients older than 45 years of age performed worse than younger patients, with female patients older than 45 years of age demonstrating the lowest outcome scores. In the age group of 45 years or younger, female patients performed as well as male patients in terms of hip clinical outcome scores. Overall, care must be individualized to optimize outcomes following hip arthroscopy for femoroacetabular impingement. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence. PMID- 27194490 TI - Capital Femoral Growth Plate Extension Predicts Cam Morphology in a Longitudinal Radiographic Study. AB - BACKGROUND: Recent evidence has suggested that cam morphology may be related to alterations in the capital femoral growth plate during adolescence. The purpose of this study was to evaluate the relationship between capital femoral growth plate extension and cam morphology in a longitudinal radiographic study. METHODS: We used a historical, longitudinal radiographic collection to identify 96 healthy adolescents (54 boys and 42 girls) with at least 5 consecutive annual radiographs of the left hip including closure of the capital femoral physis. We reviewed 554 anteroposterior radiographs of the left hip to measure the anteroposterior modification of the alpha angle of Notzli and of the superior epiphyseal extension ratio (EER), measured as the ratio of extension of the capital femoral epiphysis down the femoral neck relative to the diameter of the femoral head. Measurements were made at 3 points in femoral head maturation corresponding to the Oxford bone age (OBA) femoral head stages 5, 6, and 7/8. RESULTS: There was a mean increase in the anteroposterior alpha angle (10.7 degrees +/- 14.0 degrees ) and EER (0.12 +/- 0.08) between OBA stages 5 and 7/8, corresponding to maturation and closure of the capital femoral physis. There was a positive correlation between the final anteroposterior alpha angle and both the final EER (r = 0.60) and the change in the EER (r = 0.58). A receiver operating characteristic curve generated to predict an anteroposterior alpha angle of >=78 degrees through the EER demonstrated an area under the curve of 0.93, indicating that an increasing EER had excellent diagnostic accuracy for predicting concurrent cam morphology. CONCLUSIONS AND CLINICAL RELEVANCE: Superior epiphyseal extension was directly and temporally associated with an increase in anteroposterior alpha angle and more cam-like morphology. This alteration in the capital femoral epiphysis occurred immediately before physeal closure (OBA stage 7/8). Given the association of epiphyseal extension with activities that increase shear forces across the physis, we proposed that epiphyseal extension may be an adaptive mechanism to stabilize the physis and prevent slipped capital femoral epiphysis. PMID- 27194491 TI - The Effectiveness of the Latarjet Procedure in Patients with Chronic Locked Anterior Shoulder Dislocation: A Retrospective Study. AB - BACKGROUND: Chronic locked anterior shoulder dislocation is a difficult clinical problem for patients and surgeons. Prior studies have proposed a variety of surgical techniques to address this problem; however, the failure rate is high. To our knowledge, there have been no previously published studies on the clinical outcome of the Latarjet procedure for the treatment of chronic locked anterior shoulder dislocation. The purpose of this study was to evaluate the short-term subjective, objective, and radiographic outcomes of patients with chronic locked anterior shoulder dislocation after a Latarjet procedure. METHODS: From January 2005 to January 2013, 43 patients with chronic locked anterior shoulder dislocation were treated surgically in our institution. Open Latarjet procedures were performed in 35 patients. A subscapularis tenotomy or split was chosen on the basis of the ability to achieve open reduction. Outcomes were assessed preoperatively and postoperatively with the American Shoulder and Elbow Surgeons (ASES) score, the visual analog scale (VAS) for pain, the University of California Los Angeles (UCLA) shoulder rating scale, and the Constant-Murley rating scale. A comparison of the clinical outcomes among the patients who underwent subscapularis tenotomy and repair, those who underwent a procedure that used the subscapularis-splitting technique, and those who underwent a concomitant humeral head replacement was performed. RESULTS: Twenty-five shoulders of 25 patients were available for a mean follow-up of 31.6 months. At the time of the latest follow-up, the range of motion and the shoulder functional evaluations (VAS [p = 0.02], ASES [p = 0.01], Constant score [p = 0.01], and UCLA score [p = 0.04]) were significantly improved. The overall redislocation or subluxation rate was 48% (12 of 25): 0% (0 of 5) for the subscapularis-splitting group, 53% (8 of 15) for the subscapularis tenotomy and repair group, and 80% (4 of 5) for the humeral head replacement group. The ASES score (p = 0.006), UCLA score (p = 0.014), Constant score (p = 0.046), and external rotation (p = 0.048) were significantly better, and less severe glenohumeral osteoarthritis was found in patients who had undergone a Latarjet procedure with subscapularis-splitting compared with those who had undergone subscapularis tenotomy and repair. CONCLUSIONS: The Latarjet procedure for the treatment of chronic locked anterior shoulder dislocation can be successful if the shoulder reduction can be performed without requiring a subscapularis tenotomy. If this reduction is not possible, then other surgical reconstruction should be considered. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. PMID- 27194492 TI - Predicting Occurrence of Spine Surgery Complications Using "Big Data" Modeling of an Administrative Claims Database. AB - BACKGROUND: Postoperative metrics are increasingly important in determining standards of quality for physicians and hospitals. Although complications following spinal surgery have been described, procedural and patient variables have yet to be incorporated into a predictive model of adverse-event occurrence. We sought to develop a predictive model of complication occurrence after spine surgery. METHODS: We used longitudinal prospective data from a national claims database and developed a predictive model incorporating complication type and frequency of occurrence following spine surgery procedures. We structured our model to assess the impact of features such as preoperative diagnosis, patient comorbidities, location in the spine, anterior versus posterior approach, whether fusion had been performed, whether instrumentation had been used, number of levels, and use of bone morphogenetic protein (BMP). We assessed a variety of adverse events. Prediction models were built using logistic regression with additive main effects and logistic regression with main effects as well as all 2 and 3-factor interactions. Least absolute shrinkage and selection operator (LASSO) regularization was used to select features. Competing approaches included boosted additive trees and the classification and regression trees (CART) algorithm. The final prediction performance was evaluated by estimating the area under a receiver operating characteristic curve (AUC) as predictions were applied to independent validation data and compared with the Charlson comorbidity score. RESULTS: The model was developed from 279,135 records of patients with a minimum duration of follow-up of 30 days. Preliminary assessment showed an adverse-event rate of 13.95%, well within norms reported in the literature. We used the first 80% of the records for training (to predict adverse events) and the remaining 20% of the records for validation. There was remarkable similarity among methods, with an AUC of 0.70 for predicting the occurrence of adverse events. The AUC using the Charlson comorbidity score was 0.61. The described model was more accurate than Charlson scoring (p < 0.01). CONCLUSIONS: We present a modeling effort based on administrative claims data that predicts the occurrence of complications after spine surgery. CLINICAL RELEVANCE: We believe that the development of a predictive modeling tool illustrating the risk of complication occurrence after spine surgery will aid in patient counseling and improve the accuracy of risk modeling strategies. PMID- 27194493 TI - Combined Intra-Articular and Intravenous Tranexamic Acid Reduces Blood Loss in Total Knee Arthroplasty: A Randomized, Double-Blind, Placebo-Controlled Trial. AB - BACKGROUND: In total knee arthroplasty, both intravenous (IV) and intra-articular (IA) administration of tranexamic acid (TXA) have been shown to reduce blood loss in several randomized controlled trials, although routine use of systemic TXA is considerably more common. However, to our knowledge, the additional benefit of IA administration of TXA when combined with IV administration, without the use of a tourniquet, has not been previously investigated. Thus, the aim of this study was to evaluate whether combined IV and IA administration of TXA reduced total blood loss compared with IV-only administration of TXA. METHODS: In this randomized, double-blind, placebo-controlled trial, 60 patients scheduled for total knee arthroplasty were randomized to one of two interventions. The TXA IV and IA group received combined administration of TXA consisting of 1 g administered intravenously preoperatively and 3 g diluted in 100 mL of saline solution administered intra-articularly after closure of the capsule. The TXA IV and placebo group received 1 g of TXA administered intravenously only and 100 mL of saline solution administered intra-articularly. IA TXA was administrated through a needle. The primary outcome was the 24-hour calculated blood loss. Secondary outcomes were blood loss on postoperative day 2, thromboembolic complications, and transfusion rate. Blood loss was calculated by hemoglobin differences using the Gross formula. RESULTS: Data on the primary outcome were available for all 60 included patients. Baseline characteristics were comparable between the allocation groups. The mean 24-hour blood loss (and standard deviation) was 466 +/- 313 mL in the TXA IV and IA group compared with 743 +/- 358 mL in the TXA IV and placebo group; treatment effect (difference), 277 mL (95% confidence interval [CI], 103 to 451 mL) (p = 0.002). Second-day blood loss was 644 +/- 382 mL in the TXA IV and IA group compared with 1017 +/- 519 mL in the TXA IV and placebo group; treatment effect, 373 mL (95% CI, 132 to 614 mL) (p = 0.003). No thromboembolic complications were observed within 90 days postoperatively. CONCLUSIONS: The combined administration of IV and IA TXA resulted in a clinically relevant reduction in blood loss of 37% compared with IV TXA alone both at 24 hours postoperatively and on postoperative day 2. No thromboembolic complications were observed. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence. PMID- 27194494 TI - Systematic Quantification of Stabilizing Effects of Subtalar Joint Soft-Tissue Constraints in a Novel Cadaveric Model. AB - BACKGROUND: Distinguishing between ankle instability and subtalar joint instability is challenging because the contributions of the subtalar joint's soft tissue constraints are poorly understood. This study quantified the effects on joint stability of systematic sectioning of these constraints followed by application of torsional and drawer loads simulating a manual clinical examination. METHODS: Subtalar joint motion in response to carefully controlled inversion, eversion, internal rotation, and external rotation moments and multidirectional drawer forces was quantified in fresh-frozen cadaver limbs. Sequential measurements were obtained under axial load approximating a non-weight bearing clinical setting with the foot in neutral, 10 degrees of dorsiflexion, and 10 degrees and 20 degrees of plantar flexion. The contributions of the components of the inferior extensor retinaculum were documented after incremental sectioning. The calcaneofibular, cervical, and interosseous talocalcaneal ligaments were then sectioned sequentially, in two different orders, to produce five different ligament-insufficiency scenarios. RESULTS: Incremental detachment of the components of the inferior extensor retinaculum had no effect on subtalar motion independent of foot position. Regardless of the subsequent ligament sectioning order, significant motion increases relative to the intact condition occurred only after transection of the calcaneofibular ligament. Sectioning of this ligament produced increased inversion and external rotation, which was most evident with the foot dorsiflexed. CONCLUSIONS: Calcaneofibular ligament disruption results in increases in subtalar inversion and external rotation that might be detectable during a manual examination. Insufficiency of other subtalar joint constraints may result in motion increases that are too subtle to be perceptible. CLINICAL RELEVANCE: If calcaneofibular ligament insufficiency is established, its reconstruction or repair should receive priority over that of other ankle or subtalar periarticular soft-tissue structures. PMID- 27194495 TI - Percent Body Fat Is More Predictive of Function After Total Joint Arthroplasty Than Body Mass Index. AB - BACKGROUND: Obesity has an important impact on the future of total joint arthroplasty; however, the definition and influence of obesity on surgical risks and outcomes remain controversial. Our hypothesis was that percent body fat was better than body mass index (BMI) at identifying clinical risks and patient reported functional outcomes following arthroplasty. METHODS: Clinical and functional outcomes were collected prospectively in 215 patients undergoing primary total knee arthroplasty (115 patients) or total hip arthroplasty (100 patients) at a mean time of twenty-four months (range, twelve to forty months). Clinical data included patient demographic characteristics, preoperative evaluation including measurements of BMI and percent body fat, intraoperative records, hospital course or events, and postoperative outpatient follow-up. Patient-reported outcomes were obtained through a series of questionnaires: a surgical satisfaction survey; the University of California, Los Angeles (UCLA) activity scale; the Knee Injury and Osteoarthritis Outcome Score (KOOS) for total knee arthroplasty; and the Hip Disability and Osteoarthritis Outcome Score (HOOS) for total hip arthroplasty. Multivariable regression models were used to identify significant body mass predictors of outcomes (p < 0.05). RESULTS: Higher percent body fat predicted occurrence of any medical or surgical complication (odds ratio per one standard deviation increase, 1.58 [95% confidence interval, 1.04 to 2.40]; p = 0.033). Percent body fat was also a predictor of the UCLA activity score (risk ratio, 0.92 [95% confidence interval, 0.85 to 0.98]; p = 0.013) and pain scores (risk ratio, 1.18 [95% confidence interval, 1.03 to 1.36]; p = 0.017), and it trended toward significance for the surgical satisfaction score (odds ratio, 1.96 [95% confidence interval, 0.93 to 4.15]; p = 0.078), whereas BMI was not predictive of these functional outcomes. Additionally, with regard to surgical procedure-specific outcome scores, percent body fat was predictive of outcomes after total knee arthroplasty (KOOS pain, p = 0.015, and KOOS activities of daily living, p = 0.002), but not for those after total hip arthroplasty. CONCLUSIONS: Percent body fat should be considered when predicting clinical and functional outcomes at two years following total joint arthroplasty. Percent body fat may help surgeons to improve risk stratifications, to project patient reported functional outcomes, and to better educate obese patients with regard to postoperative expectations prior to undergoing elective total joint arthroplasty. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence. PMID- 27194496 TI - Racial and Socioeconomic Disparities in Hip Fracture Care. AB - BACKGROUND: Despite declines in both the incidence of and mortality following hip fracture, there are racial and socioeconomic disparities in treatment access and outcomes. We evaluated the presence and implications of disparities in delivery of care, hypothesizing that race and community socioeconomic characteristics would influence quality of care for patients with a hip fracture. METHODS: We collected data from the New York State Department of Health Statewide Planning and Research Cooperative System (SPARCS), which prospectively captures information on all discharges from nonfederal acute-care hospitals in New York State. Records for 197,290 New York State residents who underwent surgery for a hip fracture between 1998 and 2010 in New York State were identified from SPARCS using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. Multivariable regression models were used to evaluate the association of patient characteristics, social deprivation, and hospital/surgeon volume with time from admission to surgery, in-hospital complications, readmission, and 1-year mortality. RESULTS: After adjusting for patient and surgery characteristics, hospital/surgeon volume, social deprivation, and other variables, black patients were at greater risk for delayed surgery (odds ratio [OR] = 1.49; 95% confidence interval [CI] = 1.42, 1.57), a reoperation (hazard ratio [HR] = 1.21; CI = 1.11, 1.32), readmission (OR = 1.17; CI = 1.11, 1.22), and 1-year mortality (HR = 1.13; CI = 1.07, 1.21) than white patients. Subgroup analyses showed a greater risk for delayed surgery for black and Asian patients compared with white patients, regardless of social deprivation. Additionally, there was a greater risk for readmission for black patients compared with white patients, regardless of social deprivation. Compared with Medicare patients, Medicaid patients were at increased risk for delayed surgery (OR = 1.17; CI = 1.10, 1.24) whereas privately insured patients were at decreased risk for delayed surgery (OR = 0.77; CI = 0.74, 0.81), readmission (OR = 0.77; CI = 0.74, 0.81), complications (OR = 0.80; CI = 0.77, 0.84), and 1-year mortality (HR = 0.80; CI = 0.75, 0.85). CONCLUSIONS: There are race and insurance based disparities in delivery of care for patients with hip fracture, some of which persist after adjusting for social deprivation. In addition to investigation into reasons contributing to disparities, targeted interventions should be developed to mitigate effects of disparities on patients at greatest risk. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence. PMID- 27194497 TI - Skill Acquisition and Retention Following Simulation-Based Training in Pavlik Harness Application. AB - BACKGROUND: Simulation-based learning is increasingly prevalent in many surgical training programs, as medical education moves toward competency-based curricula. In orthopaedic surgery, developmental dysplasia of the hip is a commonly treated condition, where the standard of care for patients less than six months of age is an orthotic device such as the Pavlik harness. However, despite widespread use of the Pavlik harness and the potential complications that may arise from inappropriate application, we know of no previously described formal training curriculum for Pavlik harness application. METHODS: We developed a video and model-based simulation learning module for Pavlik harness application. Two novice groups (residents and allied health professionals) were exposed to the module and, at pre-intervention, post-intervention, and retention testing, were evaluated on their ability to apply a Pavlik harness to the model. Evaluations were completed using a previously validated Objective Structured Assessment of Technical Skills (OSATS) and a global rating scale (GRS) specific to Pavlik harness application. A control group that did not undergo the module was also evaluated at two time points to determine if exposure to the Pavlik harness alone would affect skill acquisition. All groups were compared with a group of clinical experts, whose scores were used as a competency benchmark. Statistical analysis of skill acquisition and retention was conducted using t tests and analysis of variance (ANOVA). RESULTS: Exposure to the learning module improved resident and allied health professionals' competency in applying a Pavlik harness (p < 0.05) to the level of the expert clinicians, and this level of competency was retained one month after exposure to the module. Control subjects who were not exposed to the module did not improve, nor did they achieve competency. CONCLUSIONS: The simulation-based learning module was shown to be an effective tool for teaching the application of a Pavlik harness, and learners demonstrated retainable skills post-intervention. This learning module can form the cornerstone of formal teaching of Pavlik harness application for developmental dysplasia of the hip. PMID- 27194498 TI - Wound Irrigation Pressure Did Not Affect Reoperation Rate After Open Fracture Repair, but Normal Saline Solution Was Better Than Castile Soap. PMID- 27194499 TI - Hamstring Autograft Had Better Long-Term Survivorship Than Tibialis Posterior Tendon Allograft for Anterior Cruciate Ligament Reconstruction. PMID- 27194500 TI - Total Knee Replacement Plus Nonsurgical Treatment Was Better Than Nonsurgical Treatment Alone for Knee Osteoarthritis. PMID- 27194501 TI - What's New in Foot and Ankle Surgery. PMID- 27194502 TI - Patient-Centered Care and Population Health: Establishing Their Role in the Orthopaedic Practice. AB - As health care increasingly emphasizes high value, the terms "population health" and "patient-centered care" have become common, but their application is less clear. Patient-centered care encourages using data to optimize care for an individual. Population health offers a framework to consider how to efficiently and effectively manage a condition for a population, how prevention affects large groups, and the specific distribution of a given disorder. Integrating both concepts into practice can facilitate required outcome-measure reporting and potentially improve patient outcomes. Clinical practice guidelines and appropriate use criteria are examples of reconciliation of these topics. By embracing attempts to decrease variation in treating musculoskeletal disorders while personalizing delivery to individual patients, surgeons may benefit from the improvement of both efficiency and patient experience. PMID- 27194503 TI - Publication Productivity and Experience: Factors Associated with Academic Rank Among Orthopaedic Surgery Faculty in the United States. AB - BACKGROUND: Many factors play a role in academic promotion among orthopaedic surgeons. This study specifically examined the importance of publication productivity metrics, career duration, and sex on academic rank in orthopaedic surgery programs in the United States. METHODS: Faculty at 142 civilian academic orthopaedic surgery departments in 2014 were identified. Geographic region, department size, and 3 specific faculty characteristics (sex, career duration, and academic position) were recorded. The Hirsch index (h-index), defined as the number (h) of an investigator's publications that have been cited at least h times, was recorded for each surgeon. The m-index was also calculated by dividing the h-index by career duration in years. Thresholds for the h-index and the m index were identified between junior and senior academic ranks. Multivariate analysis was used to determine whether the 3 physician factors correlated independently with academic rank. RESULTS: The analysis included 4,663 orthopaedic surgeons at 142 academic institutions (24.7% clinical faculty and 75.3% academic faculty). Among academic faculty, the median h-index was 5, the median career duration was 15 years, and the median m-index was 0.37. Thresholds between junior and senior faculty status were 12 for the h-index and 0.51 for the m-index. Female academic faculty had a lower median h-index (3 compared with 5; p < 0.001) and career duration (10 years compared with 16 years; p < 0.001) than male academic faculty, but had a similar median m-index (0.33 compared with 0.38; p = 0.103). A higher h-index and longer career duration correlated independently with an increased probability of senior academic rank (p < 0.001), but sex did not (p = 0.217). CONCLUSIONS: This analysis demonstrates that a higher h-index and m-index correlate with a higher academic orthopaedic faculty rank. Although female surgeons had a lower median h-index and a shorter median career duration than male surgeons, their m-index was not significantly different, and thus sex was not an independent predictor for senior academic rank. The identified thresholds (h-index of 12 and m-index of 0.51) between junior and senior academic ranks may be considered as factors in promotion considerations. PMID- 27194504 TI - Classification and Diagnostic Criteria of Femoroacetabular Impingement Are Essential for Clinical Outcome Evaluation: Commentary on an article by Rachel M. Frank, MD, et al., "Outcomes for Hip Arthroscopy According to Sex and Age: A Comparative Matched-Group Analysis". PMID- 27194505 TI - The Rise of Structural Osteoarthritis of the Hip: Commentary on an article by William Z. Morris, MD, et al.: "Capital Femoral Growth Plate Extension Predicts Cam Morphology in a Longitudinal Radiographic Study". PMID- 27194506 TI - Is There a Role for Body Fat Determination in Total Joint Arthroplasty? Commentary on an article by Cameron K. Ledford, MD, et al.: "Percent Body Fat Is More Predictive of Function After Total Joint Arthroplasty Than Body Mass Index". PMID- 27194507 TI - Progress on lipid extraction from wet algal biomass for biodiesel production. AB - Lipid recovery and purification from microalgal cells continues to be a significant bottleneck in biodiesel production due to high costs involved and a high energy demand. Therefore, there is a considerable necessity to develop an extraction method which meets the essential requirements of being safe, cost effective, robust, efficient, selective, environmentally friendly, feasible for large-scale production and free of product contamination. The use of wet concentrated algal biomass as a feedstock for oil extraction is especially desirable as it would avoid the requirement for further concentration and/or drying. This would save considerable costs and circumvent at least two lengthy processes during algae-based oil production. This article provides an overview on recent progress that has been made on the extraction of lipids from wet algal biomass. The biggest contributing factors appear to be the composition of algal cell walls, pre-treatments of biomass and the use of solvents (e.g. a solvent mixture or solvent-free lipid extraction). We compare recently developed wet extraction processes for oleaginous microalgae and make recommendations towards future research to improve lipid extraction from wet algal biomass. PMID- 27194509 TI - Effect of finishing instrumentation using NiTi hand files on volume, surface area and uninstrumented surfaces in C-shaped root canal systems. AB - AIM: To assess the effect of 90 degrees -oscillatory instrumentation with hand files on several morphological parameters (volume, surface area and uninstrumented surface) in C-shaped root canals after instrumentation using a single-file reciprocation system (Reciproc; VDW, Munich, Germany) and a Self Adjusting File System (SAF; ReDent Nova, Ra'anana, Israel). METHODOLOGY: Twenty mandibular second molars with C-shaped canals and C1 canal configurations were divided into two groups (n = 10) and instrumented with Reciproc and SAF instruments. A size 30 NiTi hand K-file attached to a 90 degrees -oscillatory motion handpiece was used as final instrumentation in both groups. The specimens were scanned using micro-computed tomography after all procedures. Volume, surface area increase and uninstrumented root canal surface were analysed using CTAn software (Bruker-microCT, Kontich, Belgium). Also, the uninstrumented root canal surface was calculated for each canal third. All values were compared between groups using the Mann-Whitney test and within groups using the Wilcoxon's signed-rank test. RESULTS: Instrumentation with Reciproc significantly increased canal volume compared with instrumentation with SAF. Additionally, the canal volumes were significantly increased after 90 degrees -oscillatory instrumentation (between and within group comparison; (P < 0.05)). Regarding the increase in surface area after all instrumentation protocols, statistical analysis only revealed significant differences in the within groups comparison (P < 0.05). Reciproc and SAF instrumentation yielded an uninstrumented root canal surface of 28% and 34%, respectively, which was not significantly different (P > 0.05). Final oscillatory instrumentation significantly reduced the uninstrumented root canal surface from 28% to 9% (Reciproc) and from 34% to 15% (SAF; P < 0.05). The apical and middle thirds exhibited larger uninstrumented root canal surfaces after the first instrumentation that was significantly reduced after oscillatory instrumentation (P < 0.05). CONCLUSIONS: The Reciproc and SAF system were associated with similar morphological parameters after instrumentation of mandibular second molars with C-shaped canals except for a higher canal volume increase in the Reciproc group compared to the SAF. Furthermore, the final use of 90 degrees -oscillatory instrumentation using NiTi hand files significantly decreased the uninstrumented canal walls that remained after Reciproc and SAF instrumentation. PMID- 27194510 TI - Post-synthetic modifications of cadmium-based knots and links. AB - Three topologically non-trivial cadmium(ii)-based complexes-Cd-[2]C, Cd-TK and Cd SL-were simultaneously self-assembled in a dynamic library, individually isolated and fully characterized using solid-state, gas-phase and solution-phase techniques. Post-synthetic modifications, including reduction and transmetalation, were subsequently achieved. Imine bond reduction followed by demetallation led to the isolation of the corresponding organic molecules [2]C, TK and SL. Transmetalation of Cd-TK and Cd-SL with the zinc(ii) cation resulted in isolation of the corresponding zinc(ii)-containing complexes Zn-TK and Zn-SL. PMID- 27194508 TI - NMR Fragment Screening Hit Induces Plasticity of BRD7/9 Bromodomains. AB - The complex biology associated with inhibition of bromodomain and extra-terminal (BET) domains by chemical probes has attracted increasing attention, and there is a need to identify non-BET bromodomain (BD) inhibitors. Several potent inhibitors of the BRD9 BD have recently been discovered, with anticancer and anti inflammation activity. However, its paralogue, BRD7 BD, remains unexploited. Here, we identified new chemotypes targeting BRD7 BD by using NMR fragment-based screening. BRD7/9 BDs exhibit similar patterns of chemical-shift perturbation upon the titration of hit compound 1. The crystal structure revealed that 1 repels the Y222 group of BRD9 BD in a similar way to that for butyryllysine, but not acetyllysine and known inhibitors. Hit 1 induced less rearrangement of residue F161 of BRD9 BD than acetyllysine, butyryllysine, and crotonyllysine. Our study provides structural insight into a new generation of butyryllysine mimics for probing the function of BRD7/9 BD. PMID- 27194512 TI - Small Compartment Toxicity: CN VIII and Quality of Life: Hearing Loss, Tinnitus, and Balance Disorders. AB - Life experiences, industrial/environmental exposures, and administration of Food and Drug Administration (FDA)-approved drugs may have unintended but detrimental effects on peripheral and central auditory pathways. Most relevant to the readership of this journal is the role that drug treatments approved by the FDA as safe and effective appear to interact with 3 independent modes of toxicity within the small compartment of the ear. What may seem to be trivial drug-induced toxicity has the potential to change important measures of quality of life and functional capacity of mid- to late-life patients. Drugs meant to treat can become the source of interference in the activities of daily living, and as a result, treatment compliance may be jeopardized. Ototoxicity has been defined as the tendency of certain therapeutic agents and other chemical substances to cause functional impairments and cellular degeneration of the tissues of the inner ear resulting in hearing loss. However, one of the largest contributors to hospitalizations is fall-related injuries in the elderly patients associated with disorders of vestibular function linked to progressive and drug-induced toxicities. Tinnitus affects 35 to 50 million adults representing approximately 25% of the US population, with 12 million seeking medical care and 2 to 3 million reporting symptoms that were severely debilitating. This review is intended to highlight these targets of neurotoxicity that threaten the usefulness of drug treatments deemed safe and effective prior to access by the general public. PMID- 27194511 TI - Sustained, localized salicylic acid delivery enhances diabetic bone regeneration via prolonged mitigation of inflammation. AB - Diabetes is a metabolic disorder caused by insulin resistance and/or deficiency and impairs bone quality and bone healing due to altered gene expression, reduced vascularization, and prolonged inflammation. No effective treatments for diabetic bone healing are currently available, and most existing treatments do not directly address the diabetic complications that impair bone healing. We recently demonstrated that sustained and localized delivery of salicylic acid (SA) via an SA-based polymer provides a low-cost approach to enhance diabetic bone regeneration. Herein, we report mechanistic studies that delve into the biological action and local pharmacokinetics of SA-releasing polymers shown to enhance diabetic bone regeneration. The results suggest that low SA concentrations were locally maintained at the bone defect site for more than 1 month. As a result of the sustained SA release, a significantly reduced inflammation was observed in diabetic animals, which in turn, yielded reduced osteoclast density and activity, as well as increased osteoblastogenesis. Based upon these results, localized and sustained SA delivery from the SA-based polymer effectively improved bone regeneration in diabetic animals by affecting both osteoclasts and osteoblasts, thereby providing a positive basis for clinical treatments. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2595-2603, 2016. PMID- 27194513 TI - A simple and efficient ultrasonic-assisted extraction procedure combined with UV Vis spectrophotometry for the pre-concentration and determination of folic acid (vitamin B9) in various sample matrices. AB - A simple and efficient ultrasonic-assisted extraction (UAE) procedure has been proposed for the pre-concentration of (2S)-2-[(4-{[(2-amino-4-hydroxypteridin yl)methyl]amino}phenyl)formamido]pentanedioic acid (folic acid) in vegetables, pharmaceuticals and foods prior to determination at 540 nm using UV-Vis spectrophotometry. The method is based on hydrophobic ternary complex formation of folic acid with silver ions in the presence of cetyltrimethylammonium bromide (CTAB) as a sensitivity enhancer counter ion at pH 7.0, and then extraction into a micellar phase of polyethylene glycol monoalkyl ether (Genapol X-080). The impacts on the extraction efficiency and complex formation of analytical parameters such as sample pH, concentration of silver, concentration of surfactants and extraction time, ultrasonic time and sample volume, were investigated and optimised in detail. The matrix effect on the pre-concentration and determination of folic acid was investigated, and it was observed that the proposed method was highly selective against possible matrix co-extractives. Under optimised conditions, a good linear relationship between the analytical signal and folic acid concentration was obtained in the range of 0.6-180 MUg l( 1) with a detection limit of 0.19 MUg l(-1) and quantification limit of 0.63 MUg l(-1). The applicability was evaluated using samples fortified at different concentration levels, and recoveries higher than 94.1% were obtained. The precision as the percent relative standard deviation (RSD%) was in range of 2.5 3.8% (10 and 40 MUg l(-1), n = 5). The proposed method was validated by analysis of two standard reference materials (SRMs) and various real samples, and satisfactory results were obtained. PMID- 27194514 TI - Failure of combination therapy for Staphylococcus aureus bone infection: a case of in vivo selection with resistance to rifampicin and fusidic acid. AB - Staphylococcus aureus is one of the main etiologies of bone and device-related infections. Treatment of these orthopedic infections combines mostly rifampicin with other antibiotics. The recurrence or failure rate after fusidic acid/rifampicin treatment remains low (<10%). We discuss here a case of antibiotic treatment failure for Staphylococcus aureus bone infection with in vivo selection of rifampicin and fusidic acid resistance. We also report a new mutation in fusA gene involved in fusidic acid resistance. PMID- 27194515 TI - A Qualitative Study Investigating the Continued Adoption of Breaking Free Online Across a National Substance Misuse Organisation: Theoretical Conceptualisation of Staff Perceptions. AB - There is evidence for the effectiveness of computer-assisted therapies (CAT) in healthcare; however, implementing CAT can be challenging due to new technologies being perceived as 'disruptive'. This study used normalisation process theory (NPT) to investigate how Breaking Free Online (BFO), a treatment programme for substance misuse, is embedded as normal practice within Crime Reduction Initiatives (CRI), a health and social care charity. Interviews were conducted with CRI staff regarding their perceptions of the normalisation of BFO. Thematic analyses were used and findings structured around NPT. Results suggest that staff understood the benefits of BFO, particularly for those with a dual diagnosis. However, there was some confusion surrounding job roles and difficulties with the availability of resources. Whilst normalisation of BFO is progressing within CRI, there are still some challenges. Clarification of the roles of staff and peer mentors is an area in which further work is being conducted. PMID- 27194516 TI - Estimation of peptide N-Calpha bond cleavage efficiency during MALDI-ISD using a cyclic peptide. AB - Matrix-assisted laser desorption/ionization in-source decay (MALDI-ISD) induces N Calpha bond cleavage via hydrogen transfer from the matrix to the peptide backbone, which produces a c'/z* fragment pair. Subsequently, the z* generates z' and [z + matrix] fragments via further radical reactions because of the low stability of the z*. In the present study, we investigated MALDI-ISD of a cyclic peptide. The N-Calpha bond cleavage in the cyclic peptide by MALDI-ISD produced the hydrogen-abundant peptide radical [M + 2H](+) * with a radical site on the alpha-carbon atom, which then reacted with the matrix to give [M + 3H](+) and [M + H + matrix](+) . For 1,5-diaminonaphthalene (1,5-DAN) adducts with z fragments, post-source decay of [M + H + 1,5-DAN](+) generated from the cyclic peptide showed predominant loss of an amino acid with 1,5-DAN. Additionally, MALDI-ISD with Fourier transform-ion cyclotron resonance mass spectrometry allowed for the detection of both [M + 3H](+) and [M + H](+) with two (13) C atoms. These results strongly suggested that [M + 3H](+) and [M + H + 1,5-DAN](+) were formed by N Calpha bond cleavage with further radical reactions. As a consequence, the cleavage efficiency of the N-Calpha bond during MALDI-ISD could be estimated by the ratio of the intensity of [M + H](+) and [M + 3H](+) in the Fourier transform ion cyclotron resonance spectrum. Because the reduction efficiency of a matrix for the cyclic peptide cyclo(Arg-Gly-Asp-D-Phe-Val) was correlated to its tendency to cleave the N-Calpha bond in linear peptides, the present method could allow the evaluation of the efficiency of N-Calpha bond cleavage for MALDI matrix development. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27194517 TI - Stepped collisional energy MS(All) : an analytical approach for optimal MS/MS acquisition of complex mixture with diverse physicochemical properties. AB - The analysis of complex mixtures is becoming increasingly important in various fields, such as nutrition, medicinal plants and metabolomics. The components contained in such complex mixtures are always characterized with diverse physiochemical properties that pose a major challenge during the optimization of various parameters using liquid chromatography-mass spectrometer (LC-MS). The parameter 'CE energy' that is normally set at a fixed value with a moderate range of CE spread during data-dependent acquisition (DDA) analysis, a prevalent approach for untargeted identification, often fails to generate sufficient MS/MS fragment ions for untargeted identification of components from complex mixtures. Here we developed a simple and generally applicable acquisition method named stepped MS(All) (sMS(All) ) in this study, aiming to obtain optimal MS/MS spectra for identification of chemically diverse compounds from complex mixtures. sMS(All) collects serial MS(All) scans acquired at low CE to gradually ramped-up high CE values in a cycle that conventional DDA scans cannot afford. The resultant MS/MS spectra of each compound were compared and evaluated among serial MS(All) scans, and the optimal spectra were used for identification. An untargeted data analysis strategy was then employed to analyze these optimal MS/MS spectra by searching common diagnostic ions and connecting the diagnostic ion families into a network via bridging components. This sMS(All) -based route enables identification of 71 natural products from a herbal preparation, whereas only 53 out of 71 compounds were identified using the classical DDA approach. Therefore, the sMS(All) -based approach is expected to find its wide applications for characterization of vastly diverse compounds with no priori knowledge from various complex mixtures. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27194518 TI - ESI-MS/MS of expanded porphyrins: a look into their structure and aromaticity. AB - Electrospray mass spectrometry/mass spectrometry was used to investigate the gas phase properties of protonated expanded porphyrins, in order to correlate those with their structure and conformation. We have selected five expanded meso pentafluorophenyl porphyrins, respectively, a pair of oxidized/reduced fused pentaphyrins (22 and 24 pi electrons), a pair of oxidized/reduced regular hexaphyrins (26 and 28 pi electrons) and a regular doubly N-fused hexaphyrin (28 pi electrons). The gas-phase behavior of the protonated species of oxidized and reduced expanded porphyrins is different. The oxidized species (aromatic Huckel systems) fragment more extensively, mainly by the loss of two HF molecules. The reduced species (Mobius aromatic or Mobius-like aromatic systems) fragment less than their oxidized counterparts because of their increased flexibility. The protonated regular doubly fused hexaphyrin (non-aromatic Huckel system) shows the least fragmentation even at higher collision energies. In general, cyclization through losses of HF molecules decreases from the aromatic Huckel systems to Mobius aromatic or Mobius-like aromatic systems to non-aromatic Huckel systems and is related to an increase in conformational distortion. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27194520 TI - Screening of synthetic phosphodiesterase-5 inhibitors in herbal dietary supplements using transmission-mode desorption electrospray and high-resolution mass spectrometry. PMID- 27194519 TI - Development of a mass spectrometric hydroxyl-position determination method for the hydroxyindole metabolites of JWH-018 by GC-MS/MS. AB - One of the many issues of designer drugs of abuse like synthetic cannabinoids (SCs) such as JWH-018 is that details on their metabolism has yet to be fully elucidated and that multiple metabolites exist. The presence of isomeric compounds poses further challenges in their identification. Our group has previously shown the effectiveness of gas chromatography-electron ionization tandem mass spectrometry (GC-EI-MS/MS) in the mass spectrometric differentiation of the positional isomers of the naphthoylindole-type SC JWH-081, and speculated that the same approach could be used for the metabolite isomers. Using JWH-018 as a model SC, the aim of this study was to differentiate the positional isomers of its hydroxyindole metabolites by GC-MS/MS. Standard compounds of JWH-018 and its hydroxyindole metabolite positional isomers were first analyzed by GC-EI-MS in full scan mode, which was only able to differentiate the 4-hydroxyindole isomer. Further GC-MS/MS analysis was performed by selecting m/z 302 as the precursor ion. All four isomers produced characteristic product ions that enabled the differentiation between them. Using these ions, MRM analysis was performed on the urine of JWH-018 administered mice and determined the hydroxyl positions to be at the 6-position on the indole ring. GC-EI-MS/MS allowed for the regioisomeric differentiation of the hydroxyindole metabolite isomers of JWH-018. Furthermore, analysis of the fragmentation patterns suggests that the present method has high potential to be extended to hydroxyindole metabolites of other naphthoylindole type SCs in identifying the position of the hydroxyl group on the indole ring. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27194521 TI - Characterization of chemical constituents in Rhodiola Crenulate by high performance liquid chromatography coupled with Fourier-transform ion cyclotron resonance mass spectrometer (HPLC-FT-ICR MS). AB - In this work, an approach using high-performance liquid chromatography coupled with diode-array detection and Fourier-transform ion cyclotron resonance mass spectrometer (HPLC-FT-ICR MS) for the identification and profiling of chemical constituents in Rhodiola crenulata was developed for the first time. The chromatographic separation was achieved on an Inertsil ODS-3 column (150 mm * 4.6 mm,3 um) using a gradient elution program, and the detection was performed on a Bruker Solarix 7.0 T mass spectrometer equipped with electrospray ionization source in both positive and negative modes. Under the optimized conditions, a total of 48 chemical compounds, including 26 alcohols and their glycosides, 12 flavonoids and their glycosides, 5 flavanols and gallic acid derivatives, 4 organic acids and 1 cyanogenic glycoside were identified or tentatively characterized. The results indicated that the developed HPLC-FT-ICR MS method with ultra-high sensitivity and resolution is suitable for identifying and characterizing the chemical constituents in R. crenulata. And it provides a helpful chemical basis for further research on R. crenulata. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27194522 TI - Microwave plasma torch mass spectrometry for the direct detection of copper and molybdenum ions in aqueous liquids. AB - Microwave plasma torch (MPT) is a simple and low power-consumption ambient ion source. And the MPT Mass spectra of many metal elements usually exhibit some novel features different from their inductively coupled plasma (ICP) mass spectra, which may be helpful for metal element analysis. Here, we presented the results about the MPT mass spectra of copper and molybdenum elements by a linear ion trap mass spectrometer (LTQ). The generated copper or molybdenum contained ions in plasma were characterized further in collision-induced dissociated (CID) experiments. These researches built a novel, direct and sensitive method for the direct analysis of trace levels of copper and molybdenum in aqueous liquids. Quantitative results showed that the limit of detection (LOD) by using MS(2) procedure was estimated to be 0.265 ug/l (ppb) for copper and 0.497 ug/l for molybdenum. The linear dynamics ranges cover at least 2 orders of magnitude and the analysis of a single aqueous sample can be completed in 5-6 min with a reasonable semi-quantitative sense. Two practical aqueous samples, milk and urine, were also analyzed qualitatively with reasonable recovery rates and RSD. These experimental data demonstrated that the MPT MS is able to turn into a promising and hopeful tool in field analysis of copper and molybdenum ions in water and some aqueous media, and can be applied in many fields, such as environmental controlling, hydrogeology, and water quality inspection. Moreover, MPT MS could also be used as the supplement of ICP-MS for the rapid and in-situ analysis of metal ions. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27194523 TI - Shift reagents in ion mobility spectrometry: the effect of the number of interaction sites, size and interaction energies on the mobilities of valinol and ethanolamine. AB - Overlapping peaks interfere in ion mobility spectrometry (IMS), but they are separated introducing mobility shift reagents (SR) in the buffer gas forming adducts with different collision cross-sections (size). IMS separations using SR depend on the ion mobility shifts which are governed by adduct's size and interaction energies (stabilities). Mobility shifts of valinol and ethanolamine ions were measured by electrospray-ionization ion mobility-mass spectrometry (MS). Methyl-chloro propionate (M) was used as SR; 2-butanol (B) and nitrobenzene (N) were used for comparison. Density functional theory was used for calculations. B produced the smallest mobility shifts because of its small size. M and N have two strong interaction sites (oxygen atoms) and similar molecular mass, and they should produce similar shifts. For both ethanolamine and valinol ions, stabilities were larger for N adducts than those of M. With ethanolamine, M produced a 68% shift, large compared to that using N, 61%, because M has a third weak interaction site on the chlorine atom and, therefore, M has more interaction possibilities than N. This third site overrode the oxygen atoms' interaction energy that favored the adduction of ethanolamine with N over that with M. On the contrary, with valinol mobility shifts were larger with N than with M (21 vs 18%) because interaction energy favored even more adduction of valinol with N than with M; that is, the interaction energy difference between adducts of valinol with M and N was larger than that between those adducts with ethanolamine, and the third M interaction could not override this larger difference. Mobility shifts were explained based on the number of SR's interaction sites, size of ions and SR, and SR-ion interaction energies. This is the first time that the number of interaction sites is used to explain mobility shifts in SR-assisted IMS. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27194524 TI - Application to Photocatalytic H2 Production of a Whole-Cell Reaction by Recombinant Escherichia coli Cells Expressing [FeFe]-Hydrogenase and Maturases Genes. AB - A photocatalytic H2 production system using an inorganic-bio hybrid photocatalyst could contribute to the efficient utilization of solar energy, but would require the development of a new approach for preparing a H2 -forming biocatalyst. In the present study, we constructed a recombinant strain of Escherichia coli expressing the genes encoding the [FeFe]-hydrogenase and relevant maturases from Clostridium acetobutylicum NBRC 13948 for use as a biocatalyst. We investigated the direct application of a whole-cell of the recombinant E. coli. The combination of TiO2 , methylviologen, and the recombinant E. coli formed H2 under light irradiation, demonstrating that whole cells of the recombinant E. coli could be employed for photocatalytic H2 production without any time-consuming and costly manipulations (for example, enzyme purification). This is the first report of the direct application of a whole-cell reaction of recombinant E. coli to photocatalytic H2 production. PMID- 27194525 TI - The Toxic Effect of ALLN on Primary Rat Retinal Neurons. AB - N-acetyl-leucyl-leucyl-norleucinal (ALLN), an inhibitor of proteasomes and calpain, is widely used to reduce proteasomes or calpain-mediated cell death in rodents. However, ALLN is toxic to retinal neurons to some extent. At the concentration of 10 MUM, ALLN is non-toxic to cortical neurons, but induces cell death of retinal neurons in vitro. The tolerance concentration of ALLN for retinal neurons is unclear, and the precise mechanism of cell death induced by ALLN remains elusive. In this study, we investigated the toxic effect of ALLN on primary retinal neurons. The 3-(4,5-dimethylthiazole-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay showed no significant changes of cell viability at 1 MUM but decreased cell viability after treatment of ALLN at 2.5, 5, and 7.5 MUM. Lactate dehydrogenase (LDH) release was highly elevated and propidium iodide (PI)-positive cells were significantly increased at 2.5, 5, and 7.5 MUM after all treatment times. Moreover, the protein levels of caspase-3 were up-regulated at 5 and 7.5 MUM after 12 and 24 h of ALLN treatment. The ratio of Bax/Bcl-2 was raised and Annexin V-positive cells were increased at 5 and 7.5 MUM after 12 and 24 h of ALLN treatment. However, there were no significant changes in either the ratio of microtubule-associated protein 1 light chain 3 (LC3) II/LC3 I or monodansylcadaverine (MDC) staining. Our data clearly show that at the concentrations equal to and higher than 2.5 MUM, ALLN may induce cell death of primary retinal neurons by necrosis and apoptosis, but not autophagy. These suggest that primary retinal neurons are more susceptible to ALLN treatment and provide a possible mechanism for the cell death of ALLN-sensitive cells in ALLN injury. PMID- 27194527 TI - Transport and selective chaining of bidisperse particles in a travelling wave potential. AB - We combine experiments, theory and numerical simulation to investigate the dynamics of a binary suspension of paramagnetic colloidal particles dispersed in water and transported above a stripe-patterned magnetic garnet film. The substrate generates a one-dimensional periodic energy landscape above its surface. The application of an elliptically polarized rotating magnetic field causes the landscape to translate, inducing direct transport of paramagnetic particles placed above the film. The ellipticity of the applied field can be used to control and tune the interparticle interactions, from net repulsive to net attractive. When considering particles of two distinct sizes, we find that, depending on their elevation above the surface of the magnetic substrate, the particles feel effectively different potentials, resulting in different mobilities. We exploit this feature to induce selective chaining for certain values of the applied field parameters. In particular, when driving two types of particles, we force only one type to condense into travelling parallel chains. These chains confine the movement of the other non-chaining particles within narrow colloidal channels. This phenomenon is explained by considering the balance of pairwise magnetic forces between the particles and their individual coupling with the travelling landscape. PMID- 27194528 TI - Predictors of Health Care Seeking Behavior During Pregnancy, Delivery, and the Postnatal Period in Rural Tanzania. AB - Objectives Four antenatal visits, delivery in a health facility, and three postnatal visits are the World Health Organization recommendations for women to optimize maternal health outcomes. This study examines maternal compliance with the full recommended maternal health visits in rural Tanzania with the goal of illuminating interventions to reduce inequalities in maternal health. Methods Analysis included 907 women who had given birth within two years preceding a survey of women of reproductive age. Multinomial logistic regression was used to assess the influence of maternal, household, and community-level characteristics on four alternative classes defining relative compliance with optimal configuration of maternal health care seeking behavior. Results Parity, wealth index, timeliness of ANC initiation, nearest health facility type, religion, and district of residence were significant predictors of maternal health care seeking when adjusted for other factors. Multiparous women compared to primiparous were less likely to seek care at the high level [RRR 0.16, 95 % confidence interval (CI) 0.06-0.46], at the mid-level (RRR 0.22, 95 % CI 0.09-0.58), and the mid-low level (RRR 0.27, 95 % CI 0.09-0.80). Women in the highest wealth index compared to those in the poorest group were almost three times more likely to seek the highest two levels of care versus the lowest level (high RRR 2.92, 95 % CI 1.27 6.71, mid-level RRR 2.71, 95 % 1.31-5.62). Conclusion Results suggest that efforts to improve the overall impact of services on the continuum of care in rural Tanzania would derive particular benefit from strategies that improve maternal health coverage among multiparous and low socioeconomic status women. PMID- 27194526 TI - Chondroitin sulphate: a focus on osteoarthritis. AB - Chondroitin sulfate (CS) being a natural glycosaminoglycan is found in the cartilage and extracellular matrix. It shows clinical benefits in symptomatic osteoarthritis (OA) of the finger, knee, hip joints, low back, facial joints and other diseases due to its anti-inflammatory activity. It also helps in OA by providing resistance to compression, maintaining the structural integrity, homeostasis, slows breakdown and reduces pain in sore muscles. It is most often used in combination with glucosamine to treat OA. CS is a key role player in the regulation of cell development, cell adhesion, proliferation, and differentiation. Its commercial applications have been continuously explored in the engineering of biological tissues and its combination with other biopolymers to formulate scaffolds which promote and accelerate the regeneration of damaged structure. It is approved in the USA as a dietary supplement for OA, while it is used as a symptomatic slow-acting drug (SYSADOA) in Europe and some other countries. Any significant side effects or overdoses of CS have not been reported in clinical trials suggesting its long-term safety. This review highlights the potential of CS, either alone or in combination with other drugs, to attract the scientists engaged in OA treatment and management across the world. PMID- 27194529 TI - The Ulcerative Colitis Endoscopic Index of Severity is Useful to Predict Medium- to Long-Term Prognosis in Ulcerative Colitis Patients with Clinical Remission. AB - BACKGROUND: The ulcerative colitis endoscopic index of severity [UCEIS] is a validated scoring system. Nevertheless, few studies have investigated its usefulness in clinical settings. In this study, we aimed to predict the clinical prognosis of patients with ulcerative colitis [UC] in clinical remission using the UCEIS. METHODS: A total of 285 UC patients who underwent a colonoscopy between April 2012 and March 2013 were enrolled. We reviewed clinical characteristics and endoscopic scores at the time of the colonoscopy and checked the clinical remission rate of the patients until September 2015. Clinical remission and recurrence were defined as a partial Mayo score of <=1 and >=3, respectively. RESULTS: UCEIS was strongly correlated with the Mayo endoscopic score [r=0.93], moderately correlated with clinical severity [r=0.64] and mildly correlated with C-reactive protein [r=0.34]. The recurrence rate increased gradually as it became more endoscopically severe [5.0% for UCEIS=0, 22.4% for UCEIS=1, 27.0% for UCEIS=2, 35.7% for UCEIS=3 and 75.0% for UCEIS=4-5] in patients with clinical remission. UCEIS and the concomitant use of thiopurine were independent factors predicting clinical recurrence. A multivariate analysis indicated that the absence of bleeding [p<=0.001] and the absence of mucosal damage [p<0.001] in a colonoscopy were independent factors for prolongation of clinical remission. CONCLUSION: The UCEIS is useful to predict the medium- to long-term outcomes of UC patients with clinical remission. The absence of bleeding or mucosal damage is important for maintaining clinical remission. PMID- 27194530 TI - Direct and Indirect Effects of Tofacitinib on Treatment Satisfaction in Patients with Ulcerative Colitis. AB - BACKGROUND AND AIMS: This mediation modelling analysis evaluated direct and indirect effects of tofacitinib, an oral, small molecule Janus kinase inhibitor under investigation for ulcerative colitis, on patient treatment satisfaction. METHODS: Data from an 8-week randomized Phase 2 trial [NCT00787202] in adults with moderate-to-severe, active ulcerative colitis receiving twice-daily tofacitinib 0.5-15mg [n=146] or placebo [n=48] were analysed in patient-reported [n=149] and clinician-reported [n=170] outcomes-based mediation models. Binary predictor variable: Treatment [pooled active treatment vs placebo]. Eventual dependent variable: Week 8 patient treatment satisfaction [measured on a five point Likert scale]. Mediators of treatment effect on satisfaction: Week 8 Inflammatory Bowel Disease Questionnaire domains [Bowel Symptoms, Emotional Health, Social Function and Systemic Symptoms] and Mayo scale domains [Stool Frequency, Rectal Bleeding, Physician's Global Assessment and Endoscopic Disease Activity] for patient-reported and clinician-reported models, respectively. RESULTS: Overall tofacitinib indirect effect on satisfaction via Inflammatory Bowel Disease Questionnaire domains was 40.5% [p<0.05] and via Mayo scale domains was 84.0% [p<0.01] for patient-reported and clinician-reported models, respectively. Bowel function had the most important indirect effect: of the total tofacitinib effect on satisfaction, 32.4% [p=0.05] was indirectly mediated via Bowel Symptoms; and 30.0% [p=0.04] via Stool Frequency. In total, 59.5% [p<0.01] and only 16.0% [p=0.56] of tofacitinib's effect on satisfaction was unrelated to Inflammatory Bowel Disease Questionnaire and Mayo scale domains in the patient reported and clinician-reported models, respectively. CONCLUSIONS: Bowel function is an important factor for patient treatment satisfaction with tofacitinib. Treatment effect on patient satisfaction was almost completely mediated via improvement in Mayo scale domains. PMID- 27194531 TI - Genetic Deletion of Tissue Inhibitor of Metalloproteinase-1/TIMP-1 Alters Inflammation and Attenuates Fibrosis in Dextran Sodium Sulphate-induced Murine Models of Colitis. AB - BACKGROUND AND AIMS: Increased levels of tissue inhibitor of metalloproteinase-1 [TIMP-1] have been detected in both inflammatory and fibrotic lesions in Crohn's disease. In a murine model of chronic inflammation, fibrosis was associated with an increase in TIMP-1 and inhibition of matrix metalloproteinase [MMP]-mediated degradation. We investigated the effect of TIMP-1 deficiency in acute and chronic murine models of colitis. METHODS: Colitis was induced via oral administration of dextran sodium sulphate [DSS] to B6.129S4-Timp1tm1Pds/J knock-out [KO] and C57BL/6J wild-type [WT] mice. Levels of inflammation and fibrosis were assessed and gelatin zymographies and gene expression microarrays were performed. RESULTS: Compared with WT mice, TIMP-1 KO mice had higher inflammatory parameters after acute DSS administration and developed less fibrosis after chronic DSS administration. MMP-2 levels were increased in WT versus TIMP-1 KO mice with acute colitis, whereas a trend for higher proMMP-9 levels was observed in WT versus TIMP-1 KO mice with chronic colitis. In control conditions, several immune related genes [e.g Ido1, Cldn8] were differentially expressed between young TIMP 1 KO and WT mice, but to a lesser extent between older TIMP-1 KO and WT mice. In response to DSS, the gene expression pattern was significantly different between young TIMP-1 KO and WT mice, whereas it was similar in older TIMP-1 KO and WT mice. CONCLUSIONS: TIMP-1 deficiency leads to differential expression of immune related genes and to attenuated development of fibrosis. Unravelling the role of TIMP-1 in intestinal remodelling is necessary to develop more effective and more targeted therapeutic strategies for intestinal fibrosis. PMID- 27194532 TI - Symptomatic Patency Capsule Retention in Suspected Crohn's Disease. AB - The main limitation of capsule endoscopy is the risk of capsule retention. In patients with suspected Crohn's disease, however, this complication is rare, and if a small bowel stenosis is not reliably excluded, small bowel patency can be confirmed with the Pillcam patency capsule. We present two patients examined for suspected Crohn's disease who experienced significant symptoms from a retained patency capsule. Both patients had Crohn's disease located in the terminal ileum. In one patient, the patency capsule caused abdominal pain and vomiting and was visualized at magnetic resonance enterography 9 days after ingestion. Symptoms improved spontaneously. Another patient experienced small bowel perforation with severe peritonitis caused by an intact patency capsule wedged in a small bowel stricture. We conclude that the Pillcam patency capsule is an effective modality for securing small bowel patency prior to capsule endoscopy. However, it should be emphasized that delayed patency capsule degradation and symptomatic capsule retention is a rare but potentially severe complication which should be treated aggressively, either medically or endoscopically. PMID- 27194533 TI - IBD: In Food We Trust. AB - BACKGROUND AND AIMS: Both science and patients associate diet with inflammatory bowel disease [IBD]. There is no doubt that links between IBD and diet are numerous, based on both epidemiological studies and experimental studies. However, scientific evidence to support dietary advice is currently lacking, and dietary counselling for IBD patients is often limited in clinical practice to the improvement of nutrient intake. This review aimed to focus on both patient's beliefs about and molecular mechanisms for crosstalk between nutrients and inflammation. METHODS: A literature search using PubMed was performed to identify relevant studies on diet and/or nutrients and their role in IBD. Pubmed [from inception to January 20, 2016] was searched using the terms: 'Crohn', 'colitis',' intestinal epithelial cells', and a list of terms relating to diet or numerous specific nutrients. Terms associated with nutrients were individually tested in the context of IBD. Reference lists from studies selected were manually searched to identify further relevant reports. Manuscripts about diet in the context of IBD from basic science, epidemiological studies, or clinical trials were selected and reviewed. Only articles published in English were included. RESULTS: Epidemiological studies highlight the key role of diet in IBD development, and many IBD patients report diet as a triggering factor in relapse of disease. In addition, we present research on the impact of nutrients on innate immunity. CONCLUSION: Diet may offer an alternative approach to restoring deficient innate immunity in IBD, and this may be the scientific rationale for providing dietary counselling for IBD patients. PMID- 27194535 TI - Mechanical properties and biocompatibility of co-axially electrospun polyvinyl alcohol/maghemite. AB - Electrospinning is a simple and efficient process in producing nanofibers. To fabricate nanofibers made of a blend of two constituent materials, co-axial electrospinning method is an option. In this method, the constituent materials contained in separate barrels are simultaneously injected using two syringe nozzles arranged co-axially and the materials mix during the spraying process forming core and shell of the nanofibers. In this study, co-axial electrospinning method is used to fabricate nanofibers made of polyvinyl alcohol and maghemite (gamma-Fe2O3). The concentration of polyvinyl alcohol and amount of maghemite nanoparticle loading were varied, at 5 and 10 w/v% and at 1-10 v/v%, respectively. The mechanical properties (strength and Young's modulus), porosity, and biocompatibility properties (contact angle and cell viability) of the electrospun mats were evaluated, with the same mats fabricated by regular single nozzle electrospinning method as the control. The co-axial electrospinning method is able to fabricate the expected polyvinyl alcohol/maghemite nanofiber mats. It was noticed that the polyvinyl alcohol/maghemite electrospun mats have lower mechanical properties (i.e. strength and stiffness) and porosity, more hydrophilicity (i.e. lower contact angle), and similar cell viability compared to the mats fabricated by single-nozzle electrospinning method. PMID- 27194536 TI - HCV inter-subtype 1a/1b recombinant detected by complete-genome next-generation sequencing. AB - Next-generation sequencing (NGS) provides a practical approach to HCV complete genome sequencing, detecting low-frequency variants and allowing analysis of viral genetic diversity (quasispecies) in the sample, and so far, it is very useful for identifying preexisting drug-resistant mutants and emerging escape mutations, as well as detecting viral recombinants containing genomic regions from different genotypes and subtypes. The aim of this study was to analyze the complete coding region of hepatitis C virus (HCV) genotype 1 (subtypes 1a and 1b) from patients with chronic infection who were direct-acting antiviral (DAA) naive. Next-generation sequencing (Ion TorrentTM PGM) was used to determine the sequence of the complete coding region of 100 HCV-monoinfected DAA-naive patients (51 and 49 subtypes 1a and 1b, respectively). We report the first description of nearly complete HCV genome sequences of subtype 1a and 1b isolates from a large population of Brazilian patients with chronic hepatitis C, and HCV-1a grouped in two different clades. Using this methodology, an inter-subtype 1a/1b recombinant was identified in this study. PMID- 27194537 TI - Atrial ectopy and N-terminal pro-B-type natriuretic peptide as predictors of atrial fibrillation: a population-based cohort study. AB - Aims: The risk of incident atrial fibrillation (AF) can be estimated by clinical parameters in the Framingham AF risk model. Elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) and increased rate of premature atrial contractions (PACs) have been shown to be associated with AF, but the additive value of both of these biomarkers in the Framingham AF risk model has not been fully examined. Methods and results: A total of 646 subjects from the Copenhagen Holter Study (mean age 64.4 +/- 6.8 years, 41.6% women) with no history of prior AF, stroke or cardiovascular disease were followed for the diagnosis of incident AF or death (median follow-up time 14.4 years). Median NT-proBNP was 6.7 pmol/L (IQR: 3.6-13.5), median PAC count was 1.4 beats/h (IQR: 0.6-4.5), 71 (11.0%) subjects developed AF, and 244 (37.8%) died. Multiple Cox regression including Framingham AF risk score, log-transformed NT-proBNP, and log-transformed PAC showed a significant increase in AF hazard risk [hazard ratio (HR) 1.45, 95% confidence interval (CI) 1.14-1.85, P = 0.002; HR 1.23, 95% CI 1.09-1.39, P = 0.001]. The addition of PAC to the Framingham AF risk model significantly improved the time-dependent area under the receiver operating characteristic curve (AUC 65.6 vs. 72.6; P = 0.008), while the addition of NT-proBNP did not. Conclusion: Atrial fibrillation risk discrimination was significantly improved by the addition of PAC to the Framingham AF risk model, but not by the addition of NT-proBNP. PMID- 27194534 TI - Targeting cellular and molecular drivers of head and neck squamous cell carcinoma: current options and emerging perspectives. AB - Despite improvements in functional outcomes attributable to advances in radiotherapy, chemotherapy, surgical techniques, and imaging techniques, survival in head and neck squamous cell carcinoma (HNSCC) patients has improved only marginally during the last couple of decades, and optimal therapy has yet to be devised. Genomic complexity and intratumoral genetic heterogeneity may contribute to treatment resistance and the propensity for locoregional recurrence. Countering this, it demands a significant effort from both basic and clinical scientists in the search for more effective targeted therapies. Recent genomewide studies have provided valuable insights into the genetic basis of HNSCC, uncovering potential new therapeutic opportunities. In addition, several studies have elucidated how inflammatory, immune, and stromal cells contribute to the particular properties of these neoplasms. In the present review, we introduce recent findings on genomic aberrations resulting from whole-genome sequencing of HNSCC, we discuss how the particular microenvironment affects the pathogenesis of this disease, and we describe clinical trials exploring new perspectives on the use of combined genetic and cellular targeted therapies. PMID- 27194538 TI - 'Real-world' atrial fibrillation management in Europe: observations from the 2 year follow-up of the EURObservational Research Programme-Atrial Fibrillation General Registry Pilot Phase. AB - Aims: Atrial fibrillation (AF) is commonly associated with a high risk of stroke, thromboembolism, and mortality. The 1-year follow-up of the EURObservational Research Programme-Atrial Fibrillation (EORP-AF) Pilot Registry demonstrated a high mortality but good outcomes with European Society of Cardiology guideline adherent therapy. Whether these 'real-world' observations on patients managed by European cardiologists extend to 2 years remains uncertain. Methods and results: In this report from the EORP-AF General Registry Pilot Phase, we provide data on the 2-year follow-up outcomes. Consistent with the 1-year follow-up report, only a small proportion of patients were symptomatic (24.9%), with minor differences between the different AF subtypes. Persistence of oral anticoagulant (OAC) therapy remains high at 2-years, with ~80% of patients treated with OAC. The prescribing rates of non-vitamin K antagonist oral anticoagulants are progressively increasing (13.7% at 2 years). Rate and rhythm control approaches remained consistent across the entire follow-up observation. Overall mortality rates remained high, with 5.0% of patients dead during the 2-year follow-up, mostly due to cardiovascular causes (61.8%). Atrial fibrillation readmissions were frequent, particularly related to arrhythmias and heart failure. On multivariate analyses, any cardiovascular reason for admission rather than AF was significantly associated with increased mortality during the 2-year follow-up. Conclusion: In this 2-year follow-up report from EORP-AF, mortality rates with AF remain high from cardiovascular causes, despite the high prevalent use of OAC. Improved management strategies to reduce major adverse outcomes in AF patients are needed. PMID- 27194539 TI - Plasma homocysteine levels predict early recurrence after catheter ablation of persistent atrial fibrillation. AB - AIMS: To assess the association and the predictive value of plasma homocysteine (Hcy) with early recurrence in persistent atrial fibrillation patients after a single ablation procedure. METHODS AND RESULTS: Two hundred and fifty-seven consecutive patients with persistent atrial fibrillation who underwent successful catheter ablation were enrolled. Early recurrence of atrial tachyarrhythmia was documented within 3 months after ablation. The logistic regression analysis and Kaplan-Meier curve analysis were used to evaluate the association of Hcy with early recurrence. During the 3-month follow-up, 75 (29.2%) patients experienced recurrence. Patients with early recurrence were older, more likely to have larger left atrial diameter and higher CHA2DS2-VASc score (all P< 0.001). Plasma Hcy levels were significantly elevated in patients with early recurrence compared with those without early recurrence (15.1 +/- 4.1 vs. 12.4 +/- 3.7 umol/L, P< 0.001). In multivariate analysis, Hcy was significantly associated with early recurrence (OR 1.188, 95% CI 1.097-1.286, P< 0.001). Hcy demonstrated a predictive value with AUC of 0.688 (95% CI 0.623-0.753, P< 0.001). The optimal cut-off value was 14 umol/L for Hcy (sensitivity 69%, specificity 59%). Patients with Hcy >=14 umol/L had higher early recurrence rate compared with those with Hcy <14 umol/L (41 vs. 22%, P= 0.006). CONCLUSION: Plasma Hcy levels are associated with early recurrence of atrial tachyarrhythmia after catheter ablation in persistent atrial fibrillation patients, thus it should be taken into account in prediction of early recurrence. PMID- 27194540 TI - Differential effect of ganglionic plexi ablation in a patient with neurally mediated syncope and intermittent atrioventricular block. AB - AIMS: In patients with severe neurally mediated syncope (NMS), radiofrequency catheter ablation (RFA) of ganglionic plexi (GP) has been proposed as a new therapeutic approach. Cardio-inhibitory response during NMS is usually related to the sinoatrial (SA) and less frequently to atrioventricular (AV) node. Differential effect of GP ablation on SA and AV node is poorly understood. METHODS AND RESULTS: We report a case of a 35-year-old female with frequent symptomatic episodes of advanced AV block treated by anatomically guided RFA at empirical sites of GPs. After RFA at the septal portion of the right atrium superior vena cava junction, heart rate accelerated from 62 to 91 beats/min and PR interval prolonged from 213 to 344 ms. Sustained first-degree AV block allowed to observe directly the effects of subsequent RFA on the AV nodal properties. Subsequent RFA at right- and left-sided aspects of the inter-atrial septum had no further effect on heart rate and PR interval. Ablation at the inferior left GP was critical for restoration of normal AV conduction (final PR interval of 187 ms). No bradycardia episodes were observed by implantable loop recorder during the follow-up of 10 months and the patient was symptomatically improved. CONCLUSION: This is the first clinical case showing the differential effect of GP ablation on SA and AV nodal function, and critical importance of targeting the GP at the postero-inferior left atrium. The successful procedure corroborates clinical utility of ablation treatment instead of pacemaker implantation in selected patients with cardio-inhibitory NMS. PMID- 27194541 TI - Entrapment of a diagnostic catheter in a novel multipolar basket catheter (OrionTM) during right atrial mapping. PMID- 27194542 TI - Cost effectiveness of LAA closure in patients with AF and contraindications to warfarin: comment. PMID- 27194543 TI - Arrhythmogenic right ventricular cardiomyopathy: implications of next-generation sequencing in appropriate diagnosis. AB - Aims: To evaluate potential differences in the genetic profile of cases with 'definite', 'borderline', and 'possible' arrhythmogenic right ventricular cardiomyopathy (ARVC) phenotype by 2010 task force criteria using a custom genetic panel after whole-exome analysis. Methods and results: We performed whole exome sequencing in 14 cases with the clinical diagnosis ARVC using an 'Illumina HighSeq 2000' system. We presented our initial results focused on 96 known cardiomyopathy and channelopathy genes. According to the 2010 task force criteria, 7/14 cases (50%) were classified as 'definite' phenotype, 4/14 (29%) were 'borderline', and 3/14 (21%) were diagnosed with the 'possible' phenotype. Nine out of 14 patients (64%) were males, and all were Caucasians, with an average age at genetic diagnosis of 50 +/- 15 years. Among the seven cases with the 'definite' phenotype, six (86%) had a putative desmosomal mutation, while none of the seven patients with a 'possible' or borderline task force classification phenotype hosted putative mutations in desmosomal genes. Four (57%) of them had rare variants in other dilated cardiomyopathy (DCM) genes. Conclusions: Most of the patients with 'definite' ARVC phenotype by task force 2010 host mutations in desmosomal genes. Weaker ARVC phenotypes host variants/mutations in other DCM genes and result in a disease spectrum, including DCM or phenocopies of ARVC. PMID- 27194545 TI - Impact of Telephone-Based Care Coordination on Use of Cessation Medications Posthospital Discharge: A Randomized Controlled Trial. AB - Introduction: Smokers benefit from ongoing cessation support upon leaving the hospital and returning to their home environment. This study examined the impact of telephone-delivered care coordination on utilization of and adherence to cessation pharmacotherapy after hospital discharge. Methods: Inpatient smokers (n = 606) were randomized to receive counseling with care coordination (CCC) or counseling alone (C) for smoking cessation. Both groups received written materials and telephone-based cessation counseling during hospitalization and postdischarge. CCC recipients received help in selecting, obtaining, and refilling affordable pharmacotherapy prescriptions during and after hospitalization. Study outcomes included self-reported utilization, duration of use, and type of medication during the 3 months postdischarge. Results: Of the 487 (80%) of participants completing 3-month follow-up, 211 (43.3%) reported using cessation pharmacotherapy postdischarge; this did not differ by study arm (CCC: 44.7%, C: 42.0%, p = .55). Use of pharmacotherapy postdischarge was associated with smoking at least 20 cigarettes/day at baseline (odds ratio [OR]: 1.48; 95% confidence interval [CI]: 1.00-2.19) and receipt of pharmacotherapy during hospitalization (OR: 4.00; 95% CI: 2.39-6.89). Smokers with Medicaid (OR: 2.29; 95% CI: 1.32-4.02) or other insurance (OR: 1.69; 95% CI: 1.01-2.86) were more likely to use pharmacotherapy postdischarge than those with no health care coverage. Less than one in four (23.8% of CCC; 22.2% of C) continued pharmacotherapy beyond 4 weeks. Conclusions: Supplemental care coordination did not improve use of postdischarge pharmacotherapy beyond that of inpatient treatment and behavioral counseling. Insurance coverage and use of medications during the hospitalization are associated with higher use of evidence-based treatment postdischarge. Implications: Many hospitalized smokers do not receive the benefits of cessation pharmacotherapy postdischarge and telephone quitline programs often fail to help smokers procure pharmacotherapy. Thus, effective strategies are needed to improve utilization and adherence to evidence-based cessation therapies when smokers leave the hospital. We found that use of postdischarge pharmacotherapy was strongly associated with receipt of pharmacotherapy during the hospitalization and with the availability of insurance to cover the costs of treatment. Additional efforts to coordinate pharmacotherapy services did not improve either utilization or adherence to therapy. PMID- 27194544 TI - Self-Administered Nicotine Suppresses Body Weight Gain Independent of Food Intake in Male Rats. AB - INTRODUCTION: The action of nicotine to suppress body weight is often cited as a factor impacting smoking initiation and the failure to quit. Despite the weight suppressant effects of nicotine, smokers and nonsmokers report equal daily caloric intake. The weight-suppressive effects of nicotine in animal models of smoking are poorly understood. Furthermore, the Food and Drug Administration has authority to implement a policy markedly reducing nicotine levels in cigarettes; such a reduction could reduce smoking behavior, but have detrimental effects on body weight. The aim of this investigation was to examine the effects of self administered nicotine on body weight and food intake in rats. METHODS: In Experiment 1, rats with ad libitum access to chow responded for intravenous infusions of nicotine (60 ug/kg/infusion) or saline in daily 1-hour sessions; body weight and 24-hour food intake were measured. Experiment 2 tested the effects of subcutaneous injections of nicotine on food intake. In Experiment 3, rats were food restricted and self-administered nicotine across a range of doses (3.75-60 ug/kg/infusion) while body weight was measured. In Experiment 4, rats self-administered 60 ug/kg/infusion nicotine before reduction to one of several doses (1.875-15 ug/kg/infusion) for 50 days. RESULTS: Self-administered nicotine suppressed weight gain independent of food intake. In food restricted rats, self administered nicotine dose-dependently suppressed body weight gain. In rats self administering 60 ug/kg/infusion nicotine, dose reduction increased body weight. CONCLUSIONS: Self-administered nicotine, even at low doses, suppressed body independent of food intake; this may have important implications for nicotine reduction policy. IMPLICATIONS: The results of the present studies demonstrate that self-administered nicotine suppresses body weight independent of food intake in rats. Further, the present studies establish that self-administered nicotine suppresses body weight even at very low doses and that reduction of nicotine dose results in weight gain. These results have important implications for nicotine reduction policy. PMID- 27194546 TI - Prenatal Tobacco Exposure Shortens Telomere Length in Children. AB - INTRODUCTION: Preliminary evidence suggests a possible association between prenatal tobacco exposure and telomere length in children. This study was conducted to investigate whether maternal smoking during pregnancy was associated with telomere shortening in their children and whether prenatal and childhood exposure to environmental tobacco had any impact on this association. METHODS: This is a population-representative study on the association between prenatal tobacco exposure and telomere length in children. Ninety-eight Hong Kong Chinese children aged under 15 years with prenatal tobacco exposure and 98 age- and gender-matched controls were recruited from a population health study with stratified random sampling. RESULTS: Telomere length in children with prenatal tobacco exposure was significantly shorter than in those with no exposure (mean T/S ratio = 24.9 [SD = 8.58] in exposed vs. 28.97 [14.15] in control groups; P = 0.02). A negative dose-response relationship was observed between the T/S ratio and tobacco exposure duration: the longer the duration of maternal smoking in pregnancy, the shorter the child's telomere length. The association between the child's telomere length and prenatal tobacco exposure remained significant after considering the influence of family socioeconomic status and exposure to environmental tobacco smoke during pregnancy and childhood. CONCLUSIONS: Prenatal tobacco exposure was associated with telomere shortening in children. As this may impose significant health impacts through fetal genetic programming, more efforts should be made to reduce fetal tobacco exposure by educating pregnant women to not smoke and motivating smokers to quit in early pregnancy. IMPLICATIONS: As reflected by telomere shortening, prenatal tobacco exposure in children can cause premature aging and increased health risks, which we suggest is entirely preventable. Not smoking during pregnancy or quitting smoking is critical to improving the health outcome of our future generations as prenatal tobacco exposure may affect children's biological programming. PMID- 27194547 TI - Tularemia vaccines. AB - Francisella tularensis is the causative agent of the potentially lethal disease tularemia. Due to a low infectious dose and ease of airborne transmission, Francisella is classified as a category A biological agent. Despite the possible risk to public health, there is no safe and fully licensed vaccine. A potential vaccine candidate, an attenuated live vaccine strain, does not fulfil the criteria for general use. In this review, we will summarize existing and new candidates for live attenuated and subunit vaccines. PMID- 27194548 TI - Amplification of FGFR1 gene and expression of FGFR1 protein is found in different histological types of lung carcinoma. AB - Although lung cancer continues to be the leading cause of cancer-related death, accurate diagnosis followed by personalized treatment is expected to raise the 5 year survival rate. Targeted therapies are now in routine clinical use, in particular for lung adenocarcinoma (ADC). Fibroblast growth factor receptor 1 (FGFR1) has recently emerged as a molecular target, especially in squamous cell/epidermoid carcinoma (SQC) of the lung. This paper evaluates FGFR1 expression and gene copy number in adenocarcinomas, squamous cell carcinomas, pleomorphic carcinomas (PLEOMC) and adenosquamous carcinomas (ADSQC) of the lung and also explores the epithelial-mesenchymal transition (EMT) pathway. We studied 76 lung carcinomas: 34 ADC, 24 SQC, 10 PLEOMC and 8 ADSQC. FGFR1 expression was evaluated by immunohistochemistry and gene amplification by fluorescence in situ hybridization (FISH). Higher FGFR1 protein expression was observed in all tumour types compared to non-tumour tissue. FGFR1 expression was higher in ADC and PLEOMC than in SQC. We found a tendency to higher expression in ADC than in SQC and significantly higher expression in PLEOMC than in other histological subtypes. FISH-based amplification of FGFR1 was identified in 15 (20 %) lung carcinomas: 5 (15 %) ADC, 5 (21 %) SQC, 3 (30 %) PLEOMC and 2 (25 %) ADSQC. Amplification was more frequent in SQC without significant differences. FGFR1 protein is expressed in the majority of lung carcinomas, though it is higher in ADC and PLEOMC (the latter may reflect the importance of FGFR1 control of the EMT pathway). FGFR1 amplification was identified in all types of lung carcinoma. Although FGFR1 is most frequently amplified in SQC, other histological types merit assessment of FGFR1 amplification, in order to select patients that might benefit from targeted therapy. PMID- 27194549 TI - Risk factors for hypertensive attack during pheochromocytoma resection. AB - PURPOSE: We aimed to retrospectively evaluate the risk factors for hypertensive attack during adrenalectomy in patients with pheochromocytoma. Despite the development of newer surgical and anesthetic techniques for the management of pheochromocytoma, intraoperative hypertensive attack continues to present a challenge. MATERIALS AND METHODS: Data from 53 patients diagnosed with pheochromocytoma at Kyungpook National Uriversity Medical Center between January 2000 and June 2012 were retrospectively analyzed. The subjects were divided into 2 groups depending on the presence or absence of hypertensive attack at the time of surgery. Patient demographic characteristics and preoperative evaluations were assessed for their prognostic relevance with respect to hypertensive attack. A univariate analysis was conducted, and a multivariate logistic regression analysis was also performed. RESULTS: In the univariate analysis, systolic blood pressure at presentation, preoperative hormonal status (including epinephrine, norepinephrine, vanillylmandelic acid, and metanephrine levels in a 24-hour urine sample), tumor size, and postoperative systolic blood pressure were significantly associated with the development of hypertensive attack. In the multivariate analysis, preoperative epinephrine level and tumor size were independent factors that predicted hypertensive attack. The highest odds ratio for tumor size (2.169) was obtained at a cutoff value of 4.25 cm and the highest odds ratio for preoperative epinephrine (1.020) was obtained at a cutoff value of 166.3 ug/d. CONCLUSIONS: In this study, a large tumor size and an elevated preoperative urinary epinephrine level were risk factors for intraoperative hypertensive attack in patients with pheochromocytoma. PMID- 27194550 TI - Defining and simulating open-ended novelty: requirements, guidelines, and challenges. AB - The open-endedness of a system is often defined as a continual production of novelty. Here we pin down this concept more fully by defining several types of novelty that a system may exhibit, classified as variation, innovation, and emergence. We then provide a meta-model for including levels of structure in a system's model. From there, we define an architecture suitable for building simulations of open-ended novelty-generating systems and discuss how previously proposed systems fit into this framework. We discuss the design principles applicable to those systems and close with some challenges for the community. PMID- 27194552 TI - The MELFO-Study: Prospective, Randomized, Clinical Trial for the Evaluation of a Stage-adjusted Reduced Follow-up Schedule in Cutaneous Melanoma Patients-Results after 1 Year. AB - BACKGROUND: Guidelines for evidence-based follow-up in melanoma patients are not available. This study examined whether a reduced follow-up schedule affects: patient-reported outcome measures, detection of recurrences, and follow-up costs. METHODS: This multicenter trial included 180 patients treated for AJCC stage IB II cutaneous melanoma, who were randomized in a conventional follow-up schedule group (CSG, 4 visits first year, n = 93) or experimental follow-up schedule group (ESG, 1-3 visits first year, n = 87). Patients completed the State-Trait Anxiety Inventory, cancer worry scale, impact of events scale, and a health-related quality of life questionnaire (HRQoL, RAND-36). Physicians registered clinicopathologic features and the number of outpatient clinic visits. RESULTS: Sociodemographic and illness-related characteristics were equal in both groups. After 1-year follow-up, the ESG reported significantly less cancer-related stress response symptoms than the CSG (p = 0.01), and comparable anxiety, mental HRQoL, and cancer-related worry. Mean cancer-related worry and stress response symptoms decreased over time (p < 0.001), whereas mental HRQoL increased over time (p < 0.001) in all melanoma patients. Recurrence rate was 9 % in both groups, mostly patient-detected and not physician-detected (CSG 63 %, ESG 43 %, p = 0.45). Hospital costs of 1-year follow-up were reduced by 45 % in the ESG compared to the CSG. CONCLUSIONS: This study shows that the stage-adjusted, reduced follow-up schedule did not negatively affect melanoma patients' mental well-being and the detection of recurrences compared with conventional follow-up as dictated by the Dutch guideline, at 1 year after diagnosis. Additionally, reduced follow-up was associated with significant hospital cost reduction. PMID- 27194553 TI - Completion Lymph Node Dissection or Observation for Melanoma Sentinel Lymph Node Metastases: A Decision Analysis. AB - BACKGROUND: Long-term, randomized trial results comparing completion lymph node dissection (CLND) with observation for patients with sentinel lymph node (SLN) metastases are not available. Our goal was to determine whether melanoma patients with SLN metastases should undergo CLND. METHODS: We developed a Markov model to simulate the prognosis of hypothetical cohorts of patients with SLN metastases who underwent either immediate CLND or observation with delayed CLND if macroscopic disease developed. Model parameters were derived from published studies and included the likelihood of non-SLN metastases, risk of dying from melanoma, CLND complication rates, and health-related quality-of-life weights. Outcomes included 5-year overall survival (OS), life expectancy (LE), and quality adjusted life expectancy (QALE). RESULTS: The projected 5-year OS for 50-year-old patients with SLN metastases who underwent immediate CLND was 67.2 % compared with 63.1 % for the observation group. The LE gained by undergoing immediate CLND ranged from 2.19 years for patients aged 30 to 0.64 years for patients aged 70 years. The QALE gained by undergoing immediate CLND ranged from 1.39 quality adjusted life years for patients aged 30 to 0.36 for patients aged 70 years. In sensitivity analysis over a clinically plausible range of values for each input parameter, immediate CLND was no longer beneficial when the rate of long-term complications increased and the quality-of-life weight for long-term complications decreased. CONCLUSIONS: Immediate CLND following positive SLN biopsy was associated with OS and QALE gains compared with observation and delayed CLND for those who develop clinically apparent LN metastases. PMID- 27194554 TI - The customer is always right? Subjective target symptoms and treatment preferences in patients with psychosis. AB - Clinicians and patients differ concerning the goals of treatment. Eighty individuals with schizophrenia were assessed online about which symptoms they consider the most important for treatment, as well as their experience with different interventions. Treatment of affective and neuropsychological problems was judged as more important than treatment of positive symptoms (p < 0.005). While most individuals had experience with Occupational and Sports Therapy, only a minority had received Cognitive-Behavioral Therapy, Family Therapy, and Psychoeducation with family members before. Patients appraised Talk, Psychoanalytic, and Art Therapy as well as Metacognitive Training as the most helpful treatments. Clinicians should carefully take into consideration patients' preferences, as neglect of consumers' views may compromise outcome and adherence to treatment. PMID- 27194555 TI - Review of PI3K/mTOR Inhibitors Entering Clinical Trials to Treat Triple Negative Breast Cancers. AB - BACKGROUND: Constitutive activation of the PI3K/mTOR signaling pathway is observed in most, if not all, breast cancers. Accordingly, many PI3K and/or mTOR inhibitors have entered clinical trials, and completed studies should soon reveal the efficacy of these new drug families in the treatment of cancer patients. OBJECTIVE: We present the PI3K/Akt/mTOR signaling pathway and the structure and the anti-tumor efficiency of some mTOR inhibitors such as rapalogues and competitive inhibitors, which have entered clinical trials. We also discuss some of the clinical trial results associated with these molecules mainly focusing on studies performed on relapsing breast cancer patients - but not only. RESULTS: Most of the clinical trials with PI3K/mTOR inhibitors alone or in combination with chemotherapies were performed in heavily pre-treated patients and revealed non-negligible amounts of partial responses and long-term stable disease for these patients. Therefore, these compounds seem to prevent tumor growth and survival of cancer cells in Human, representing a new range of anti-tumor drugs that can be utilized not only as first-line treatments but as second- and third line agents for patients who relapse. CONCLUSION: Drugs inhibiting the PI3K/mTOR signaling pathway may represent tailored anti-tumor agents, paving the way for their clinical application in different tumor types. PMID- 27194557 TI - Tensions of Health: Narratives of Employee Wellness Program Participants. AB - This article examines dialectical tensions in the health narratives of participants of the Employee Wellness Program (EWP) of a large public university in the southeastern United States. Semi-structured interviews (n = 12) with team leaders in the program indicated that health is a multifaceted concept characterized by three pairs of dialectical tensions: autonomy versus connection, private versus public, and control versus lack of control. These findings suggest that to better promote health and wellness in the workplace, EWP staff should consider employees' unique experiences and beliefs about health when designing organization-wide programs and campaigns. PMID- 27194556 TI - Heteroaromatic Pim Kinase Inhibitors Containing a Pyrazole Moiety. AB - This review, of the literature published between 2010 and 2015 reports that molecules containing a non-fused and/or fused pyrazole moiety could exhibit very potent activity toward Pim kinases, including the inhibition of cellular Bad phosphorylation as well as antiproliferative activity against various cancer cells. Even if Pim kinase inhibitors currently in clinical trial do not exhibit a pyrazole moiety, heteroaromatic kinase inhibitors containing an indazole part such as Axitinib and Pazopanib already reached the market. Therefore, one can imagine that in the future, heteroaromatic derivatives inhibiting Pim kinases including pyrazoles could be identified and used for their diagnostic and/or therapeutic potential alone or in combination with other drugs for the diseases in which Pim kinases are involved. PMID- 27194558 TI - Employment Maintenance and Intimate Partner Violence. AB - Intimate partner violence (IPV) is a major public health problem in the United States. Negative outcomes of IPV affect women's attainment and maintenance of employment. The purpose of this study was to develop a theoretical framework that described and explained the process by which women who have experienced IPV attain and maintain employment. Grounded theory methodology was used to analyze interviews of 34 women who had experienced IPV. Analysis suggested that women who had experienced IPV could attain employment; however, they had difficulty maintaining employment. Entanglement of work and IPV was experienced by all 34 participants because of the perpetrator controlling their appearance, sabotaging their work, interfering with their work, or controlling their finances. Some women described ways in which they disentangled work from IPV through a dynamic unraveling process, with periods of re-entanglement, resulting in job security and satisfaction. PMID- 27194559 TI - Mediastinal Adiposity Influences the Technical Difficulty of Thoracic Procedure in Minimally Invasive Esophagectomy. AB - BACKGROUND: Obesity is considered to influence the difficulty of surgery. However, whether mediastinal adiposity influences the difficulty of the thoracic procedure in minimally invasive esophagectomy (MIE) remains unclear. METHODS: Computed tomography volumetry was performed in 142 patients who underwent MIE between 2012 and 2014. We measured abdominal visceral fat area (AVFA) at the umbilicus level and mediastinal fat area (MFA) at the tracheal carina level. The influence of MFA on the difficulty of the thoracic procedure was assessed using the thoracic procedure duration as a parameter, and the effect of MFA on morbidity after MIE was assessed. RESULTS: MFA was significantly smaller than AVFA (p < 0.01). There was a positive correlation between them (p < 0.01). A significant positive correlation was observed between MFA and thoracic procedure duration (p < 0.01). Multivariate analysis revealed that MFA was independently correlated with prolonged thoracic procedure duration (p < 0.01). Regarding postoperative complications associated with the thoracic procedure, there were no significant differences in MFA between patients with or without pneumonia and those with or without chylothorax. Patients who experienced recurrent laryngeal nerve palsy (RLNP) had greater MFA than those who did not (p = 0.04). Multivariate analysis revealed that MFA was a significant predictor of the occurrence of RLNP (p = 0.04). CONCLUSIONS: Although the extent of mediastinal adiposity was much lesser than that of abdominal visceral adiposity, it could be a predictor of the difficulty of the thoracic procedure as well as the risk of RLNP in MIE. PMID- 27194561 TI - The Hernia-Neck-Ratio (HNR), a Novel Predictive Factor for Complications of Umbilical Hernia. AB - BACKGROUND: Umbilical hernia is a common pathology and surgical repair is advised to prevent complications in symptomatic patients. However, risk factors that predict such advert events are unknown. The aim of the study was to determine whether morphological characteristics are associated with the occurrence of complications. METHOD: Retrospective review of adult patients with elective and emergent umbilical hernia repair operated from January 2004 to December 2013. The size of the hernia and the size of the neck were measured based on operative reports, ultrasound, CT or MRI images. The Hernia-Neck-Ratio (HNR) was then calculated as novel risk indicator. RESULTS: 106 patients underwent umbilical hernia repair (70 for uncomplicated and 36 for complicated hernia) as single procedure. The median size of the hernia sac was statistically significantly smaller in the uncomplicated group (30 mm, interquartile range (IQR) 20-49 vs. 50 mm, IQR 40-71, p = 0.037). The median size of the neck was not different between both groups (15 mm, IQR 11-29 vs. 16 mm, IQR 12-21, p = 0.44). The median HNR was smaller in the uncomplicated group (1.76, IQR 1.45-2.18 vs. 3.33, IQR 2.97-3.91, p = 0.00026). Based on ROC curve analysis (area under the curve: 0.9038), a cut off value of 2.5 was associated with 91 % sensitivity and 84 % specificity. CONCLUSIONS: A novel predictive factor for complications related to umbilical hernia is proposed. The Hernia-Neck Ratio can easily be calculated. These results suggest that umbilical hernia with HNR >2.5 should be operated, irrespective of the presence of symptoms. PMID- 27194560 TI - Enhanced Recovery Pathway for Right and Left Colectomy: Comparison of Functional Recovery. AB - BACKGROUND: Enhanced recovery (ERAS) guidelines do not differentiate between left and right-sided colectomies, but differences in recovery have been reported for the two procedure types. We aimed to compare compliance with the ERAS protocol and outcomes after right versus left colectomy. METHODS: Between June 2011 and September 2014, all patients undergoing elective colonic resection were treated according to a standardized ERAS protocol and entered a prospective database. This retrospective analysis compared right and left colectomy regarding application of the ERAS pathway, bowel recovery, complications, and hospital stay. RESULTS: Eighty-five patients with right colectomy matched well with 138 left-sided resections for baseline demographics. Overall compliance with the ERAS protocol was 76 % for right versus 77 % for left colectomy patients (p = 0.492). First flatus occurred at postoperative day 2 in both groups (p = 0.057); first stool was observed after a median of 3 (right) and 2 days (left), respectively (p = 0.189). Twenty patients (24 %) needed postoperative nasogastric tube after right colectomy compared to 11 patients (8 %) after left colectomy (p = 0.002). Overall complication rates were 49 and 37 % for right and left colectomy, respectively (p = 0.071). Median postoperative length of stay was 6 days (IQR 4 9) after right and 5 days (IQR 4-7.5) after left colectomy (p = 0.020). CONCLUSION: Overall compliance with the protocol was equally high in both groups showing that ERAS protocol was applicable for right and left colectomy. Functional recovery however, tended to be slower after right colectomy, and postoperative ileus rate was significantly higher. More cautious early feeding after right colectomy should be considered. PMID- 27194563 TI - Succinate metabolism: a new therapeutic target for myocardial reperfusion injury. AB - Myocardial ischaemia/reperfusion (IR) injury is a major cause of death worldwide and remains a disease for which current clinical therapies are strikingly deficient. While the production of mitochondrial reactive oxygen species (ROS) is a critical driver of tissue damage upon reperfusion, the precise mechanisms underlying ROS production have remained elusive. More recently, it has been demonstrated that a specific metabolic mechanism occurs during ischaemia that underlies elevated ROS at reperfusion, suggesting a unifying model as to why so many different compounds have been found to be cardioprotective against IR injury. This review will discuss the role of the citric acid cycle intermediate succinate in IR pathology focusing on the mechanism by which this metabolite accumulates during ischaemia and how it can drive ROS production at Complex I via reverse electron transport. We will then examine the potential for manipulating succinate accumulation and metabolism during IR injury in order to protect the heart against IR damage and discuss targets for novel therapeutics designed to reduce reperfusion injury in patients. PMID- 27194564 TI - Neural response patterns in spider, blood-injection-injury and social fearful individuals: new insights from a simultaneous EEG/ECG-fMRI study. AB - In the present simultaneous EEG/ECG-fMRI study we compared the temporal and spatial characteristics of the brain responses and the cardiac activity during fear picture processing between spider, blood-injection-injury (BII) and social fearful as well as healthy (non-fearful) volunteers. All participants were presented with two neutral and six fear-related blocks of pictures: two social, two spider and two blood/injection fear blocks. In a social fear block neutral images were occasionally interspersed with photographs of angry faces and social exposure scenes. In spider and blood/injection fear blocks neutral pictures were interspersed with spider fear-relevant and blood/injection pictures, respectively. When compared to healthy controls the social fear group responded with increased activations in the anterior orbital, middle/anterior cingulate and middle/superior temporal areas for pictures depicting angry faces and with a few elevated superior frontal activations for social exposure scenes. In the blood/injection fear group, heart rate was decreased and the activity in the middle/inferior frontal and visual processing regions was increased for blood/injection pictures. The HR decrease for blood/injection pictures correlated with increased frontal responses. In the spider fear group, spider fear-relevant pictures triggered increased activations within a broad subcortical and cortical neural fear network. The HR response for spider fear-relevant stimuli was increased and correlated with an increased insula and hippocampus activity. When compared to healthy controls, all fear groups showed higher LPP amplitudes for their feared cues and an overall greater P1 hypervigilance effect. Contrasts against the fear control groups showed that the increased responses for fear specific stimuli are mostly related to specific fears and not to general anxiety proneness. The results suggest different engagement of cognitive evaluation and down-regulation strategies and an overall increased sensitization of the fear system in the three fear groups. PMID- 27194562 TI - Comparison of Salvage Living Donor Liver Transplantation and Local Regional Therapy for Recurrent Hepatocellular Carcinoma. AB - BACKGROUND AND AIMS: Salvage liver transplantation (LT) provides definite treatment for recurrent hepatocellular carcinoma (HCC) after primary liver resection. However, salvage living donor LT (SLDLT) involves more surgical difficulty, compared to local regional therapy (LRT). The optimal treatment strategy remains unclear. This study aims to compare the survival between SLDLT and LRT for patients with recurrent HCC after primary hepatic resection in a single center. METHODS: Between 2001 and 2010, 211 patients with recurrent HCC after primary liver resection and a certain Milan criteria were enrolled. Among these patients, 41 and 170 patients received SLDLT and LRT, respectively. Clinical parameters were analyzed in terms of overall survival by multivariate analysis. RESULTS: The 1-, 3-, and 5-year overall survival rates were 90.2, 80.4, and 80.4 % in the SLDLT group, and 91.6, 71.7, and 51.1 % in LRT group, respectively. A paradoxical phenomenon of survival was noticed-a poorer survival rate within the first year in the SLDLT group but a better one after that year. For patients who survived more than 1 year, the SLDLT led to significantly better survival outcomes than LRT (P < 0.001). In multivariate analysis, SLDLT and alpha fetoprotein (AFP) level < 200 ng/ml at recurrence were associated with better survival. CONCLUSIONS: To manage recurrent HCC, SLDLT with reasonable surgical mortality provided better long-term survival. AFP is an independent risk factor for overall survival. PMID- 27194567 TI - On the Variability and Increasing Trends of Heat Waves over India. AB - Over India, heat waves occur during the summer months of April to June. A gridded daily temperature data set for the period, 1961-2013 has been analyzed to examine the variability and trends in heat waves over India. For identifying heat waves, the Excess Heat Factor (EHF) and 90(th) percentile of maximum temperatures were used. Over central and northwestern parts of the country, frequency, total duration and maximum duration of heat waves are increasing. Anomalous persistent high with anti-cyclonic flow, supplemented with clear skies and depleted soil moisture are primarily responsible for the occurrence of heat waves over India. Variability of heat waves over India is influenced by both the tropical Indian Ocean and central Pacific SST anomalies. The warming of the tropical Indian Ocean and more frequent El Nino events in future may further lead to more frequent and longer lasting heat waves over India. PMID- 27194565 TI - Role of lateral septum glucagon-like peptide 1 receptors in food intake. AB - Hindbrain glucagon-like peptide 1 (GLP-1) neurons project to numerous forebrain areas, including the lateral septum (LS). Using a fluorescently labeled GLP-1 receptor (GLP-1R) agonist, Exendin 4 (Ex4), we demonstrated GLP-1 receptor binding throughout the rat LS. We examined the feeding effects of Ex4 and the GLP 1R antagonist Exendin (9-39) (Ex9) at doses subthreshold for effect when delivered to the lateral ventricle. Intra-LS Ex4 suppressed overnight chow and high-fat diet (HFD) intake, and Ex9 increased chow and HFD intake relative to vehicle. During 2-h tests, intra-LS Ex9 significantly increased 0.25 M sucrose and 4% corn oil. Ex4 can cause nausea, but intra-LS administration of Ex4 did not induce pica. Furthermore, intra-LS Ex4 had no effect on anxiety-like behavior in the elevated plus maze. We investigated the role of LS GLP-1R in motivation for food by examining operant responding for sucrose on a progressive ratio (PR) schedule, with and without a nutrient preload to maximize GLP-1 neuron activation. The preload strongly suppressed PR responding, but blockade of GLP-1R in the intermediate subdivision of the LS did not affect motivation for sucrose under either load condition. The ability of the nutrient load to suppress subsequent chow intake was significantly attenuated by intermediate LS Ex9 treatment. By contrast, blockade of GLP-1R in the dorsal subdivision of the LS increased both PR responding and overnight chow intake. Together, these studies suggest that endogenous activity of GLP-1R in the LS influence feeding, and dLS GLP-1Rs, in particular, play a role in motivation. PMID- 27194568 TI - Use of double decidual sac sign to confirm intrauterine pregnancy location prior to sonographic visualization of embryonic contents. AB - OBJECTIVES: To determine the diagnostic accuracy of the double decidual sac sign (DDSS) for predicting an intrauterine pregnancy (IUP) prior to visualization of embryonic contents, using modern high-resolution transvaginal sonography (TVS). METHODS: The study was conducted following STARD guidelines and participants were recruited prospectively from Nurture Fertility, Nottingham, UK, following in vitro fertilization/intracytoplasmic sperm injection treatment between 1 January 2015 and 31 October 2015. Women were excluded if there was no evidence of intrauterine fluid collection during the index test, a yolk sac or fetal pole was visible during the index test, no outcome data were available or pregnancy location could not be determined by the reference standard. The index test consisted of TVS at 32-34 days' gestation using a high-frequency transvaginal probe. Reference standard was TVS at 7 weeks' gestation. The outcome of interest was an IUP. RESULTS: A total of 67 intrauterine fluid collections were observed and included in the analysis, of which 61 exhibited the DDSS and 65 were proven to be IUPs. Two ectopic pregnancies were included, neither of which demonstrated the DDSS. The DDSS therefore had a sensitivity of 93.9% (95% CI, 85.0-98.3%), specificity of 100% (95% CI, 15.8-100%) and overall diagnostic accuracy of 94.0% (95% CI, 88.3-99.7%) for predicting an IUP. The negative likelihood ratio and positive and negative predictive values were 0.06 (95% CI, 0.02-0.16), 100% (95% CI, 94.1-100%) and 33.3% (95% CI, 4.3-77.7%), respectively. CONCLUSION: With modern high-resolution TVS, presence of the DDSS can be used to confirm accurately IUP location prior to sonographic visualization of embryonic contents, and therefore to exclude effectively ectopic pregnancy. Absence of the DDSS, however, does not preclude an IUP. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 27194569 TI - Structural Diversification of Lyngbyatoxin A by Host-Dependent Heterologous Expression of the tleABC Biosynthetic Gene Cluster. AB - Natural products have enormous structural diversity, yet little is known about how such diversity is achieved in nature. Here we report the structural diversification of a cyanotoxin-lyngbyatoxin A-and its biosynthetic intermediates by heterologous expression of the Streptomyces-derived tleABC biosynthetic gene cluster in three different Streptomyces hosts: S. lividans, S. albus, and S. avermitilis. Notably, the isolated lyngbyatoxin derivatives, including four new natural products, were biosynthesized by crosstalk between the heterologous tleABC gene cluster and the endogenous host enzymes. The simple strategy described here has expanded the structural diversity of lyngbyatoxin A and its biosynthetic intermediates, and provides opportunities for investigation of the currently underestimated hidden biosynthetic crosstalk. PMID- 27194570 TI - Mean arterial pressure values calculated using seven different methods and their associations with target organ deterioration in a single-center study of 1878 individuals. AB - To assess the differences among seven different methods for the calculation of mean arterial pressure (MAP) and to identify the formula that provides MAP values that are more closely associated with target organ deterioration as expressed by the carotid cross-sectional area (CSA), carotid-to-femoral pulse-wave velocity (cf-PWV) and left ventricular mass (LVM). The study population consisted of 1878 subjects who underwent noninvasive cardiovascular risk assessment. Blood pressure (BP) was assessed in all subjects, and MAP was calculated by direct oscillometry and six different formulas. Carotid artery ultrasound imaging was performed in 1628 subjects. The CSA of the right and left common carotid artery (CCA) were calculated and used as surrogates of arterial wall mass and hypertrophy. Aortic stiffness was evaluated in 1763 subjects by measuring the cf-PWV. Finally, 218 subjects underwent echocardiographic examination for the assessment of LVM. Among the examined methods of MAP calculation, the formula MAP1=[diastolic BP]+0.412 * [pulse pressure] yielded the strongest correlations with the LVM, cf-PWV and CSA of the right and left CCA, even after adjusting for age and gender. The MAP calculation using the 0.412 was superior compared with the traditional formula that uses the 0.33 for the discrimination of subjects with left ventricular and carotid wall hypertrophy, as well as subjects with increased aortic stiffness. MAP estimated with the 0.412 is better correlated with target organ deterioration compared with other formulas. Future studies are needed to explore the accuracy of these formulas for MAP estimation compared with direct intra-arterial BP measurement. PMID- 27194571 TI - Maternal home blood pressure as a predictor of infant birth weight. PMID- 27194572 TI - Effects of uric-acid-lowering therapy on renal outcomes: the future looks promising. PMID- 27194573 TI - Retinal vessel caliber and its relationship with nocturnal blood pressure dipping status: the SABPA study. AB - Adverse changes in retinal microvasculature caliber are associated with incident hypertension, coronary heart disease and stroke. The absence of a nocturnal dipping in arterial pressure may induce changes throughout the vascular tree, including the retinal microvasculature, but the later link is not sufficiently studied. We explored the relationship between retinal vessel caliber and dipping status in a group of black and white teachers. The study included black (n=68) and white (n=81) men (24-66 years) from the SABPA study. We measured 24 h ambulatory blood pressure and the percentage mean arterial pressure dipping(%MAPdip) was calculated as (diurnal MAP-nocturnal MAP)/diurnal MAP * 100. Retinal images were captured and the central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) calculated. Black men demonstrated higher diurnal and nocturnal MAP (P?0.001) and a lesser %MAPdip compared with white men (P=0.047). When stratified by dipping status, black non-dippers (n=33) revealed an increased CRVE (P<0.001) compared with their dipper counterparts (n=35). In black men, CRVE was negatively (R2=0.38, beta=-0.47, P<0.001) associated with %MAPdip independent of 24 h MAP or nocturnal MAP. CRVE also associated negatively with dipping status as a dichotomized variable (R2=0.29, beta=-0.32, P=0.006), independent of 24 h MAP. These associations were absent in the white men. In conclusion, in this group of black men, a non-dipping blood pressure profile was associated with a larger CRVE, suggesting microvascular deterioration due to the absence of nocturnal dipping in blood pressure. This may add to our understanding of the stroke risk in black populations. PMID- 27194574 TI - Left atrial enlargement and blood pressure variability in untreated hypertensive patients. PMID- 27194575 TI - Establishment of a new three-dimensional human epidermal model reconstructed from plucked hair follicle-derived keratinocytes. PMID- 27194576 TI - Comparative Transcriptomics of Alternative Developmental Phenotypes in a Marine Gastropod. AB - Alternative phenotypes are discrete phenotypic differences that develop in response to both genetic and environmental cues. Nutritive embryos, which arrest their development to serve as nutrition for their viable siblings, are an example of an alternative developmental phenotype found in many animal groups. Females of the marine snail, Crepidula navicella, produce broods that consist mainly of nutritive embryos and a small number of viable embryos. In order to better understand the genetic mechanisms that lead to the development of alternative phenotypes in this species, we compared the transcriptomes of viable and nutritive embryos at the earliest stage that we were able to distinguish visually between the two. Using high-throughput Illumina sequencing, we assembled and annotated a de novo transcriptome and compared transcript levels in viable and nutritive embryos. Viable embryos express high levels of transcripts associated with known developmental events, while nutritive embryos express high levels of apoptosis-related transcripts. Gene Ontology term enrichment with GOSeq found that these are associated with the negative regulation of apoptotic processes. This enrichment, combined with morphological evidence, suggests that apoptosis is important in the formation of gastrula-like nutritive embryos. Apoptosis has been implicated in the development of alternative phenotypes in other animal groups, raising the possibility that this mechanism's role in alternative phenotypes is conserved in gastropod development. We suggest possible alternative mechanisms of nutritive embryo development. Most importantly, we contribute further evidence to the hypothesis that nutritive embryos are an alternative developmental phenotype. PMID- 27194578 TI - Electro-mechanical sensing in freestanding monolayered gold nanoparticle membranes. AB - The electro-mechanical sensing properties of freestanding monolayered membranes of dodecanethiol coated 7 nm gold nanoparticles (NPs) are investigated using AFM force spectroscopy and conductive AFM simultaneously. The electrical resistance of the NP membranes increases sensitively with the point-load force applied in the center of the membranes using an AFM tip. Numerical simulations of electronic conduction in a hexagonally close-packed two-dimensional (2D) array of NPs under point load-deformation are carried out on the basis of electronic transport measurements at low temperatures and strain modeling of the NP membranes by finite element analysis. These simulations, supporting AFM-based electro mechanical measurements, attribute the high strain sensitivity of the monolayered NP membranes to the exponential dependence of the tunnel electron transport in 2D NP arrays on the strain-induced length variation of the interparticle junctions. This work thus evidences a new class of highly sensitive nano-electro-mechanical systems based on freestanding monolayered gold NP membranes. PMID- 27194577 TI - Predictors of renal histopathology in antineutrophil cytoplasmic antibody associated glomerulonephritis. AB - OBJECTIVES: Prompt, aggressive therapy is vital for anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis. In this regard, we aimed to identify predictors of distinct renal histopathological classes at the time of clinical diagnosis. PATIENTS & METHODS: An inception cohort of patients with biopsy proven ANCA-associated glomerulonephritis was studied retrospectively. Demographics, clinical, laboratory, serological and radiological parameters were analyzed. Patients were classified on the basis of renal histopathology. A risk score was developed for each histopathological class using univariate and stepwise logistic regression analyses. RESULTS: Variables independently associated with focal class included disease duration up to diagnosis <8 weeks, absence of erythrocyte casts by urine microscopy and eGFR >49 ml/min/1.73 m(2); with crescentic class >40 erythrocytes/hpf, identification of erythrocyte casts in urine, upper respiratory tract involvement and eGFR <49 ml/min/1.73 m(2); with mixed class age >54 years, male gender, and absence of upper respiratory tract involvement. In the presence of these risk factors a predictive risk score for each histopathological classes was calculated: odds ratio, 95% confidence intervals (CI), for focal class (>=2 risk factors, 20.8 (95% CI: 5.1-84.2), p < 0.0001, and 441.0 (95% CI: 16.8-11,590), p = 0.0003 for crescentic class (>=3 risk factors) while the small number of patients in the mixed and sclerotic class precluded any estimates. CONCLUSION: We propose a predictive algorithm of specific histolopathological classes of ANCA-associated glomerulonephritis, which might provide a crude estimation of the disease activity in the glomeruli at presentation. This tool might assist the clinician in making decisions regarding the level of intensity of inductive immunosuppressive therapy at clinical diagnosis. PMID- 27194579 TI - Modulation of tumor eIF4E by antisense inhibition: A phase I/II translational clinical trial of ISIS 183750-an antisense oligonucleotide against eIF4E-in combination with irinotecan in solid tumors and irinotecan-refractory colorectal cancer. AB - The eukaryotic translation initiation factor 4E (eIF4E) is a potent oncogene that is found to be dysregulated in 30% of human cancer, including colorectal carcinogenesis (CRC). ISIS 183750 is a second-generation antisense oligonucleotide (ASO) designed to inhibit the production of the eIF4E protein. In preclinical studies we found that EIF4e ASOs reduced expression of EIF4e mRNA and inhibited proliferation of colorectal carcinoma cells. An additive antiproliferative effect was observed in combination with irinotecan. We then performed a clinical trial evaluating this combination in patients with refractory cancer. No dose-limiting toxicities were seen but based on pharmacokinetic data and tolerability the dose of irinotecan was reduced to 160 mg/m(2) biweekly. Efficacy was evaluated in 15 patients with irinotecan refractory colorectal cancer. The median time of disease control was 22.1 weeks. After ISIS 183750 treatment, peripheral blood levels of eIF4E mRNA were decreased in 13 of 19 patients. Matched pre- and posttreatment tumor biopsies showed decreased eIF4E mRNA levels in five of nine patients. In tumor tissue, the intracellular and stromal presence of ISIS 183750 was detected by IHC in all biopsied patients. Although there were no objective responses stable disease was seen in seven of 15 (47%) patients who were progressing before study entry, six of whom were stable at the time of the week 16 CT scan. We were also able to confirm through mandatory pre- and posttherapy tumor biopsies penetration of the ASO into the site of metastasis. PMID- 27194581 TI - Soccer training programme improved the body composition of pre-adolescent boys and increased their satisfaction with their body image. PMID- 27194580 TI - Personalized blood flow computations: A hierarchical parameter estimation framework for tuning boundary conditions. AB - We propose a hierarchical parameter estimation framework for performing patient specific hemodynamic computations in arterial models, which use structured tree boundary conditions. A calibration problem is formulated at each stage of the hierarchical framework, which seeks the fixed point solution of a nonlinear system of equations. Common hemodynamic properties, like resistance and compliance, are estimated at the first stage in order to match the objectives given by clinical measurements of pressure and/or flow rate. The second stage estimates the parameters of the structured trees so as to match the values of the hemodynamic properties determined at the first stage. A key feature of the proposed method is that to ensure a large range of variation, two different structured tree parameters are personalized for each hemodynamic property. First, the second stage of the parameter estimation framework is evaluated based on the properties of the outlet boundary conditions in a full body arterial model: the calibration method converges for all structured trees in less than 10 iterations. Next, the proposed framework is successfully evaluated on a patient-specific aortic model with coarctation: only six iterations are required for the computational model to be in close agreement with the clinical measurements used as objectives, and overall, there is a good agreement between the measured and computed quantities. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27194582 TI - Genome-wide analysis of transcription factors involved in maize embryonic callus formation. AB - In this study, a maize inbred line with a strong capacity to induce embryonic callus, 18-599R, was used to analyze the transcription factors expressed during embryonic callus formation. A total of 1180 transcription factors were found to be expressed during three key stages of callus induction. Of these, compared with control, 361, 346 and 328 transcription factors were significantly downregulated during stages I, II and III, respectively. In contrast, 355, 372 and 401 transcription factors (TFs) were upregulated during the respective stages. We constructed a transcription factor-mediated regulatory network and found that plant hormone signal transduction was the pathway most significantly enriched among TFs. This pathway includes 48 TFs regulating cell enlargement, cell differentiation, cell division and cell dedifferentiation via the response to plant hormones. Through real-time polymerase chain reaction (PCR) and degradome sequencing, we identified 23 transcription factors that are regulated by miRNA. Through further analysis, ZmMYB138, a member of the MYB transcription factor family localized in the nucleus, was verified to promote embryonic callus formation in the maize embryo through GA signal transduction. PMID- 27194584 TI - Synthesis, photophysical, electrochemical and electrochemiluminescence properties of A2B2 zinc porphyrins: the effect of pi-extended conjugation. AB - The synthesis of two A2B2 porphyrins, {5,15-bis-[4-(octyloxy)phenyl] porphyrinato}zinc(ii) () and {5,15-bis-(carbazol-3-yl-ethynyl)-10,20-bis-[4 (octyloxy)phenyl]-porphinato}-zinc(ii) (), is reported. Their photophysical properties were studied by steady-state absorption and emission. Substituting the carbazolylethynyl moieties at two of the meso positions results in a large bathochromic shift of all the absorption bands, a notable increase in the absorption coefficient of the Q(0,0) band, and higher fluorescence quantum yield compared to porphyrin , with two unsubstituted meso positions. Cyclic voltammetry and digital simulation show that electrogenerated radical ions of are more stable than those of . The lack of substituents at the meso positions of leads to dimerization reactions of the radical cation. Despite this, the annihilation reaction of and produces very similar electrogenerated chemiluminescence (ECL) intensity. Spectroelectrochemical experiments demonstrate that the electroreduction of leads to a strong absorption band that might quench the ECL. PMID- 27194583 TI - Novel small molecule 11beta-HSD1 inhibitor from the endophytic fungus Penicillium commune. AB - Two new phenone derivatives penicophenones A (1) and B (2), a new cyclic tetrapeptide penicopeptide A (3), and five known compounds were isolated from the culture broth of Penicillium commune, an endophytic fungus derived from Vitis vinifera. Compounds 1-3 were elucidated by extensive spectroscopic analyses including 1D and 2D NMR and HRESIMS. The absolute configurations of 1 and 3 were determined by comparing its ECD with related molecules and modified Marfey's analysis, respectively. Penicophenone A (1) possesses a rare benzannulated 6,6 spiroketal moiety, which is a new member of the unusual structural class with peniphenone A as the representative. Compound 3 exhibited significant inhibition activities against 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) in vitro and showed strong binding affinity to 11beta-HSD1. Moreover, compound 3 treatments decreased the lipid droplet accumulation associate with the inhibition of 11beta-HSD1 expression in differentiate-induced 3T3-L1 preadipocytes. Furthermore, the molecular docking demonstrated that compound 3 coordinated in the active site of 11beta-HSD1 is essential for the ability of diminishing the enzyme activity. PMID- 27194585 TI - Temperature-induced structure switch in thermo-responsive micellar interpolyelectrolyte complexes: toward core-shell-corona and worm-like morphologies. AB - The spontaneous formation and thermo-responsiveness of a colloidally-stable interpolyelectrolyte complex (IPEC) based on a linear temperature-sensitive diblock copolymer poly(vinyl sulfonate)31-b-poly(N-isopropyl acrylamide)27 (PVS31 b-PNIPAM27) and a star-shaped quaternized miktoarm polymer poly(ethylene oxide)114-(poly(2-(dimethylamino)ethyl methacrylate)17)4 (PEO114-(qPDMAEMA17)4) was investigated in aqueous media at 0.3 M NaCl by means of dynamic light scattering (DLS), small angle X-ray scattering (SAXS), and cryogenic transmission electron microscopy (cryo-TEM). The micellar macromolecular co-assemblies show a temperature-dependent size and morphology, which result from the lower critical solution temperature (LCST) behavior of the PNIPAM-blocks. Hence, the micellar co assemblies grow upon heating. At 60 degrees C, spherical core-shell-corona co assemblies are proposed with a hydrophobic PNIPAM core, a water-insoluble IPEC shell, and a hydrophilic PEO corona. These constructs develop into a rod-like structure upon extended equilibration. In turn, PEO-arms and PNIPAM-blocks within a hydrophilic mixed two-component corona surround the water-insoluble IPEC domain at 20 degrees C, thereby forming spherical core-corona co-assemblies. Reversibility of the structural changes is suggested by the scattering data. This contribution addresses the use of a combination of oppositely charged thermo responsive and bis-hydrophilic star-shaped polymeric components toward IPECs of diverse morphological types. PMID- 27194586 TI - Inbreeding depression in Zebu cattle traits. AB - The productivity of herds may be negatively affected by inbreeding depression, and it is important to know how intense is this effect on the livestock performance. We performed a comprehensive analysis involving five Zebu breeds reared in Brazil to estimate inbreeding depression in productive and reproductive traits. Inbreeding depression was estimated for 13 traits by including the individual inbreeding rate as a linear covariate in the standard genetic evaluation models. For all breeds and for almost all traits (no effect was observed on gestation length), the performance of the animals was compromised by an increase in inbreeding. The average inbreeding depression was -0.222% and 0.859% per 1% of inbreeding for linear regression coefficients scaled on the percentage of mean (betam ) and standard deviation (betasigma ), respectively. The means for betam (and betasigma ) were -0.269% (-1.202%) for weight/growth traits and -0.174% (-0.546%) for reproductive traits. Hence, inbreeding depression is more pronounced in weight/growth traits than in reproductive traits. These findings highlight the need for the management of inbreeding in the respective breeding programmes of the breeds studied here. PMID- 27194587 TI - An in vivo invertebrate evaluation system for identifying substances that suppress sucrose-induced postprandial hyperglycemia. AB - Sucrose is a major sweetener added to various foods and beverages. Excessive intake of sucrose leads to increases in blood glucose levels, which can result in the development and exacerbation of lifestyle-related diseases such as obesity and diabetes. In this study, we established an in vivo evaluation system using silkworms to explore substances that suppress the increase in blood glucose levels caused by dietary intake of sucrose. Silkworm hemolymph glucose levels rapidly increased after intake of a sucrose-containing diet. Addition of acarbose or voglibose, alpha-glycosidase inhibitors clinically used for diabetic patients, suppressed the dietary sucrose-induced increase in the silkworm hemolymph glucose levels. Screening performed using the sucrose-induced postprandial hyperglycemic silkworm model allowed us to identify some lactic acid bacteria that inhibit the increase in silkworm hemolymph glucose levels caused by dietary intake of sucrose. The inhibitory effects of the Lactococcus lactis #Ll-1 bacterial strain were significantly greater than those of different strains of lactic acid bacteria. No effect of the Lactococcus lactis #Ll-1 strain was observed in silkworms fed a glucose diet. These results suggest that the sucrose diet-induced postprandial hyperglycemic silkworm is a useful model for evaluating chemicals and lactic acid bacteria that suppress increases in blood glucose levels. PMID- 27194589 TI - Simvastatin downregulated C35 expression and inhibited the proliferation of colon cancer cells Lovo and HT29 in vitro. AB - The aim of this study was to investigate the antitumor effect of simvastatin in human colon cancer and the possible underlying mechanism. We found that simvastatin dose-dependently inhibited the proliferation of human colon cancer cells Lovo and HT29 using a MTT assay. Real-time PCR and Western blotting assays showed that simvastatin significantly suppressed C35 expression at both mRNA and protein levels. Since C35 is known to have a significant oncogenic role in cancer development via promoting cell proliferation and migration, results obtained in the current study imply that downregulation of C35 expression might be involved in the antitumor effect of simvastatin on colon cancer. PMID- 27194590 TI - Results of human factors testing in a novel Hemodialysis system designed for ease of patient use. AB - Introduction Home hemodialysis has not been widely adopted despite superior outcomes relative to conventional in-center hemodialysis. Patients receiving home hemodialysis experience high rates of technique failure owing to machine complexity, training burden, and the inability to master treatments independently. Methods We conducted human factors testing on 15 health care professionals (HCPs) and 15 patients upon release of the defined training program on the TabloTM Hemodialysis System. Each participant completed one training and one testing session conducted in a simulated clinical environment. Training sessions lasted <3 hours for HCPs and <4 hours for patients, with an hour break between sessions for knowledge decay. During the testing session, we recorded participant behavior and data according to standard performance and safety-based criteria. Findings Of 15 HCPs, 10 were registered nurses and five patient care technicians, with a broad range of dialysis work experience and no limitations other than visual correction. Of 15 patients (average age 48 years), 13 reported no limitations and two reported modest limitations-partial deafness and blindness in one eye, respectively. The average error rate was 4.4 per session for HCPs and 2.9 per session for patients out of a total possible 1,710 opportunities for errors. Despite having received minimal training, neither HCPs nor patients committed safety-related errors that required mitigation; rather, we noted only minor errors and operational difficulties. Discussion The TabloTM Hemodialysis System is easy to use, and may help to enable self-care and home hemodialysis in settings heretofore associated with high rates of technique failure. PMID- 27194588 TI - The calcium sensor Copine-6 regulates spine structural plasticity and learning and memory. AB - Hippocampal long-term potentiation (LTP) represents the cellular response of excitatory synapses to specific patterns of high neuronal activity and is required for learning and memory. Here we identify a mechanism that requires the calcium-binding protein Copine-6 to translate the initial calcium signals into changes in spine structure. We show that Copine-6 is recruited from the cytosol of dendrites to postsynaptic spine membranes by calcium transients that precede LTP. Cpne6 knockout mice are deficient in hippocampal LTP, learning and memory. Hippocampal neurons from Cpne6 knockouts lack spine structural plasticity as do wild-type neurons that express a Copine-6 calcium mutant. The function of Copine 6 is based on its binding, activating and recruiting the Rho GTPase Rac1 to cell membranes. Consistent with this function, the LTP deficit of Cpne6 knockout mice is rescued by the actin stabilizer jasplakinolide. These data show that Copine-6 links activity-triggered calcium signals to spine structural plasticity necessary for learning and memory. PMID- 27194591 TI - Removal of electrostatic artifacts in magnetic force microscopy by controlled magnetization of the tip: application to superparamagnetic nanoparticles. AB - Magnetic force microscopy (MFM) has been demonstrated as valuable technique for the characterization of magnetic nanomaterials. To be analyzed by MFM techniques, nanomaterials are generally deposited on flat substrates, resulting in an additional contrast in MFM images due to unavoidable heterogeneous electrostatic tip-sample interactions, which cannot be easily distinguished from the magnetic one. In order to correctly interpret MFM data, a method to remove the electrostatic contributions from MFM images is needed. In this work, we propose a new MFM technique, called controlled magnetization MFM (CM-MFM), based on the in situ control of the probe magnetization state, which allows the evaluation and the elimination of electrostatic contribution in MFM images. The effectiveness of the technique is demonstrated through a challenging case study, i.e., the analysis of superparamagnetic nanoparticles in absence of applied external magnetic field. Our CM-MFM technique allowed us to acquire magnetic images depurated of the electrostatic contributions, which revealed that the magnetic field generated by the tip is sufficient to completely orient the superparamagnetic nanoparticles and that the magnetic tip-sample interaction is describable through simple models once the electrostatic artifacts are removed. PMID- 27194592 TI - The incidence, risk and functional outcomes of intracranial haemorrhage in children with inherited bleeding disorders at one haemophilia center. AB - INTRODUCTION: Intracranial haemorrhage (ICH) is the most serious bleeding event for patients with inherited bleeding disorders (IBD). The risks and long-term consequences remain unknown. AIM: This single-centre service evaluation aimed to identify the incidence, risks and long-term outcomes following ICH in patients with IBD. METHODS: The IBD database and medical notes between 1987 and 2013 were reviewed. Children without apparent neurological deficit following ICH completed standardized assessments and supplementary information sheets. RESULTS: ICH was confirmed in 38/1111 children with IBD. The overall risk of ICH amongst children with IBD was 3.4% (95% CI: 2.5, 4.7%). However, 27/38 had an ICH in the first year of life, 18 of which were in the neonatal period. In children with IBD who had an ICH, the risks of ICH in the neonatal period or first year of life were 18/38 (47%) (95% CI: 32, 63%) and 27/38 (71%) (95% CI: 55, 83%) respectively. Mortality risk from ICH in children with an IBD was 5/38 (13%) (95% CI: 5.8, 27.3 %). Ten of 32 survivors had known neurological sequelae including motor disorder deficits (MDD) while 22 had no documented evidence of neurological impairment or MDD. Re-evaluation was possible in 17/22 children, 8 of whom demonstrated evidence of MDD. After re-evaluation, the risk of significant neurological MDD from ICH increased from 31% CI (95% CI: 18, 49%) to 56% CI (95% CI: 39, 72%). CONCLUSION: Risks and consequences of ICH in IBD were highest within the neonatal period and first year of life. MDD after ICH was not reliably identified in early life and ongoing monitoring in the first decade of life will facilitate educational support or physical rehabilitation. PMID- 27194593 TI - Network analysis and cross species comparison of protein-protein interaction networks of human, mouse and rat cytochrome P450 proteins that degrade xenobiotics. AB - Cytochrome P450 (CYP) enzymes that degrade xenobiotics play a critical role in the metabolism and biotransformation of drugs and xenobiotics in humans as well as experimental animal models such as mouse and rat. These proteins function as a network collectively as well as independently. Though there are several reports on the organization, regulation and functionality of various CYP enzymes at the molecular level, the understanding of organization and functionality of these proteins at the holistic level remain unclear. The objective of this study is to understand the organization and functionality of xenobiotic degrading CYP enzymes of human, mouse and rat using network theory approaches and to study species differences that exist among them at the holistic level. For our analysis, a protein-protein interaction (PPI) network for CYP enzymes of human, mouse and rat was constructed using the STRING database. Topology, centrality, modularity and robustness analyses were performed for our predicted CYP PPI networks that were then validated by comparison with randomly generated network models. Network centrality analyses of CYP PPI networks reveal the central/hub proteins in the network. Modular analysis of the CYP PPI networks of human, mouse and rat resulted in functional clusters. These clusters were subjected to ontology and pathway enrichment analysis. The analyses show that the cluster of the human CYP PPI network is enriched with pathways principally related to xenobiotic/drug metabolism. Endo-xenobiotic crosstalk dominated in mouse and rat CYP PPI networks, and they were highly enriched with endogenous metabolic and signaling pathways. Thus, cross-species comparisons and analyses of human, mouse and rat CYP PPI networks gave insights about species differences that existed at the holistic level. More investigations from both reductionist and holistic perspectives can help understand CYP metabolism and species extrapolation in a much better way. PMID- 27194594 TI - Novel nonsense mutation of the TSC2 gene in a case of Tuberous Sclerosis Complex. PMID- 27194595 TI - Strain-induced growth instability and nanoscale surface patterning in perovskite thin films. AB - Despite extensive studies on the effects of epitaxial strain on the evolution of the lattice and properties of materials, considerably less work has explored the impact of strain on growth dynamics. In this work, we demonstrate a growth-mode transition from 2D-step flow to self-organized, nanoscale 3D-island formation in PbZr0.2Ti0.8O3/SrRuO3/SrTiO3 (001) heterostructures as the kinetics of the growth process respond to the evolution of strain. With increasing heterostructure thickness and misfit dislocation formation at the buried interface, a periodic, modulated strain field is generated that alters the adatom binding energy and, in turn, leads to a kinetic instability that drives a transition from 2D growth to ordered, 3D-island formation. The results suggest that the periodically varying binding energy can lead to inhomogeneous adsorption kinetics causing preferential growth at certain sites. This, in conjunction with the presence of an Ehrlich Schwoebel barrier, gives rise to long-range, periodically-ordered arrays of so called "wedding cake" 3D nanostructures which self-assemble along the [100] and [010]. PMID- 27194596 TI - Lack of a synergistic effect of arginine-glutamic acid on the physical stability of spray-dried bovine serum albumin. AB - Improving the physical stability of spray-dried proteins is essential for enabling pulmonary delivery of biotherapeutics as a noninvasive alternative to injections. Recently, a novel combination of two amino acids - l-arginine (l-Arg) and l-glutamic acid (l-Glu), has been reported to have synergistic protein stabilizing effects on various protein solutions. Using spray-dried bovine serum albumin (BSA) reconstituted in solution as a model protein, we investigated the synergistic effect of these amino acids on the physical stability of proteins. Five BSA solutions were prepared: (1) BSA with no amino acids (control); (2) with 50 mM l-Arg; (3) with 200 mM l-Arg, (4) with 50 mM l-Glu and (5) with 25:25 mM of Arg:Glu. All solutions were spray-dried and accelerated studies at high temperatures were performed. Following accelerated studies, monomer BSA loss was measured using SE-HPLC. We found that l-Arg significantly improved the physical stability of spray-dried BSA even at low concentrations, however, when combined with l-Glu, was ineffective at reducing monomer BSA loss. Our findings demonstrate the limitations in using Arg-Glu for the stabilization of spray-dried BSA. Furthermore, we found that a low concentration of l-Glu enhanced monomer BSA loss. These findings may have significant implications on the design of future biotherapeutic formulations. PMID- 27194599 TI - Two-step fabrication of self-catalyzed Ga-based semiconductor nanowires on Si by molecular-beam epitaxy. AB - For the epitaxial growth of Ga-based III-V semiconductor nanowires (NWs) on Si, Ga droplets could provide a clean and compatible solution in contrast to the common Au catalyst. However, the use of Ga droplets is rather limited except for that in Ga-catalyzed GaAs NW studies in a relatively narrow growth temperature (Ts) window around 620 degrees C on Si. In this paper, we have investigated the two-step growth of Ga-catalyzed III-V NWs on Si (111) substrates by molecular beam epitaxy. First, by optimizing the surface oxide, vertically aligned GaAs NWs with a high yield are obtained at Ts = 620 degrees C. Then a two-temperature procedure is adopted to preserve Ga droplets at lower Ts, which leads to an extension of Ts down to 500 degrees C for GaAs NWs. Based on this procedure, systematic morphological and structural studies for Ga-catalyzed GaAs NWs in the largest Ts range could be presented. Then within the same growth scheme, for the first time, we demonstrate Ga-catalyzed GaAs/GaSb heterostructure NWs. These GaSb NWs are axially grown on the GaAs NW sections and are pure zinc-blende single crystals. Compositional measurements confirm that the catalyst particles indeed mainly consist of Ga and GaSb sections are of high purity but with a minor composition of As. In the end, we present GaAsSb NW growth with a tunable Sb composition. Our results provide useful information for the controllable synthesis of multi-compositional Ga-catalyzed III-V semiconductor NWs on Si for heterogeneous integration. PMID- 27194598 TI - A Special Font for People with Dyslexia: Does it Work and, if so, why? AB - In 2008 Christian Boer, a Dutch artist, developed a special font ("Dyslexie") to facilitate reading in children and adults with dyslexia. The font has received a lot of media attention worldwide (e.g., TheGuardian.com, Slate.com, TheAtlantic.com, USA Today, and io9.com). Interestingly, there is barely any empirical evidence for the efficacy of Dyslexie. This study aims to examine if Dyslexie is indeed more effective than a commonly used sans serif font (Arial) and, if so, whether this can be explained by its relatively large spacing settings. Participants were 39 low-progress readers who were learning to read in English. They were asked to read four different texts in four different font conditions that were all matched on letter display size (i.e., x-height), but differed in the degree to which they were matched for spacing settings. Results showed that low-progress readers performed better (i.e., read 7% more words per minute) in Dyslexie font than in standardly spaced Arial font. However, when within-word spacing and between-word spacing of Arial font was matched to that of Dyslexie font, the difference in reading speed was no longer significant. We concluded that the efficacy of Dyslexie font is not because of its specially designed letter shapes, but because of its particular spacing settings. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27194600 TI - Techniques: Spinning organoids shed light on Zika. PMID- 27194597 TI - Long-term ferrocyanide application via deicing salts promotes the establishment of Actinomycetales assimilating ferrocyanide-derived carbon in soil. AB - Cyanides are highly toxic and produced by various microorganisms as defence strategy or to increase their competitiveness. As degradation is the most efficient way of detoxification, some microbes developed the capability to use cyanides as carbon and nitrogen source. However, it is not clear if this potential also helps to lower cyanide concentrations in roadside soils where deicing salt application leads to significant inputs of ferrocyanide. The question remains if biodegradation in soils can occur without previous photolysis. By conducting a microcosm experiment using soils with/without pre exposition to road salts spiked with (13) C-labelled ferrocyanide, we were able to confirm biodegradation and in parallel to identify bacteria using ferrocyanide as C source via DNA stable isotope probing (DNA-SIP), TRFLP fingerprinting and pyrosequencing. Bacteria assimilating (13) C were highly similar in the pre exposed soils, belonging mostly to Actinomycetales (Kineosporia, Mycobacterium, Micromonosporaceae). In the soil without pre-exposition, bacteria belonging to Acidobacteria (Gp3, Gp4, Gp6), Gemmatimonadetes (Gemmatimonas) and Gammaproteobacteria (Thermomonas, Xanthomonadaceae) used ferrocyanide as C source but not the present Actinomycetales. This indicated that (i) various bacteria are able to assimilate ferrocyanide-derived C and (ii) long-term exposition to ferrocyanide applied with deicing salts leads to Actinomycetales outcompeting other microorganisms for the use of ferrocyanide as C source. PMID- 27194601 TI - Punctuated Shutdown of Atlantic Meridional Overturning Circulation during Greenland Stadial 1. AB - The Greenland Stadial 1 (GS-1; ~12.9 to 11.65 kyr cal BP) was a period of North Atlantic cooling, thought to have been initiated by North America fresh water runoff that caused a sustained reduction of North Atlantic Meridional Overturning Circulation (AMOC), resulting in an antiphase temperature response between the hemispheres (the 'bipolar seesaw'). Here we exploit sub-fossil New Zealand kauri trees to report the first securely dated, decadally-resolved atmospheric radiocarbon ((14)C) record spanning GS-1. By precisely aligning Southern and Northern Hemisphere tree-ring (14)C records with marine (14)C sequences we document two relatively short periods of AMOC collapse during the stadial, at ~12,920-12,640 cal BP and 12,050-11,900 cal BP. In addition, our data show that the interhemispheric atmospheric (14)C offset was close to zero prior to GS-1, before reaching 'near-modern' values at ~12,660 cal BP, consistent with synchronous recovery of overturning in both hemispheres and increased Southern Ocean ventilation. Hence, sustained North Atlantic cooling across GS-1 was not driven by a prolonged AMOC reduction but probably due to an equatorward migration of the Polar Front, reducing the advection of southwesterly air masses to high latitudes. Our findings suggest opposing hemispheric temperature trends were driven by atmospheric teleconnections, rather than AMOC changes. PMID- 27194602 TI - Dopamine-loaded liposome and its application in electrochemical DNA biosensor. AB - In this study, disruption and lyophilization-rehydration of dopamine-loaded liposome and its application in electrochemical DNA biosensor was investigated. The liposomes containing soyphosphatidylcholine and cholesterol were prepared through thin-layer hydration. First, an investigation was carried out to find an appropriate lysing agent for disruption of prepared liposomes. Differential pulse voltammetry, as a high sensitive electrochemical technique, was used along with a multi-walled carbon nanotubes modified glassy carbon electrode for sensitive electrochemical detection of released dopamine from disrupted liposomes. Various lysing agents were investigated and finally, the disruption of liposomes using methanol was selected without any surfactant, because of its least fouling effect. Then, lyophilization of dopamine-loaded liposomes was carried out using sucrose as cryoprotectant. The electrochemical studies of lyophilized liposomes showed that the remained dopamine in sucrose-protected liposomes was higher than sucrose-free liposomes. Furthermore, sucrose has no interference in electrochemical studies. Then, with the addition of biotin-X-DHPE to liposome formulation, the lyophilized sucrose protected dopamine-loaded biotin-tagged liposomes were prepared and the feasibility of application of them in electrochemical DNA biosensor was investigated as signal enhancer and verified for detection of oligonucleotides. PMID- 27194603 TI - Dissipative and Autonomous Square-Wave Self-Oscillation of a Macroscopic Hybrid Self-Assembly under Continuous Light Irradiation. AB - Building a bottom-up supramolecular system to perform continuously autonomous motions will pave the way for the next generation of biomimetic mechanical systems. In biological systems, hierarchical molecular synchronization underlies the generation of spatio-temporal patterns with dissipative structures. However, it remains difficult to build such self-organized working objects via artificial techniques. Herein, we show the first example of a square-wave limit-cycle self oscillatory motion of a noncovalent assembly of oleic acid and an azobenzene derivative. The assembly steadily flips under continuous blue-light irradiation. Mechanical self-oscillation is established by successively alternating photoisomerization processes and multi-stable phase transitions. These results offer a fundamental strategy for creating a supramolecular motor that works progressively under the operation of molecule-based machines. PMID- 27194604 TI - Editorial. PMID- 27194607 TI - Polydactyly: A Review. AB - Polydactyly, also known as hyperdactyly, is a common congenital limb defect, which can present with various morphologic phenotypes. Apart from cosmetic and functional impairments, it can be the first indication of an underlying syndrome in the newborn. Usually, it follows an autosomal dominant pattern of inheritance with defects occurring in the anteroposterior patterning of limb development. Although many mutations have been discovered, teratogens have also been implicated in leading to this anomaly, thus making it of multifactorial origin. There are three polydactyly subtypes (radial, ulnar, and central), and treatment options depend on the underlying feature. PMID- 27194606 TI - Early Bubble Continuous Positive Airway Pressure: Investigating Interprofessional Best Practices for the NICU Team. AB - Premature neonates delivered <32 completed weeks gestation are unprepared to handle the physiologic demands of extrauterine life. Within the respiratory system, alveolar instability and collapse can cause decreased functional residual capacity, impaired oxygenation, and hypoxemia leading to respiratory distress syndrome. Supportive measures are indicated immediately after birth to establish physiologic stability including bubble continuous positive airway pressure (CPAP) or endotracheal intubation and mechanical ventilation. CPAP is a noninvasive, gentle mode of ventilation that can mitigate the effects of lung immaturity, but prolonged use can increase the risk for nasal breakdown. Strategies to mitigate this risk must be infused as best practices in the NICU environment. The purpose of this article is to propose an evidence-based best practice care bundle for the early initiation of CPAP in the delivery room and associated skin barrier protection strategies for premature neonates <32 weeks gestation and weighing <1,500 g. PMID- 27194608 TI - Integrated Evaluation of Neonatal Hemodynamics Program Optimizing Organ Perfusion and Performance in Critically Ill Neonates, Part 1: Understanding Physiology of Neonatal Hemodynamics. AB - Integrated evaluation of neonatal hemodynamics is the integration of information obtained by echocardiography, clinical evaluation, and biochemical markers, in addition to the clinical information obtained from noninvasive and invasive monitoring of blood pressure and arterial and tissue oxygenation, leading to the formulation of a medical recommendation. This review will focus on the physiology of cardiovascular dynamics and oxygen delivery. PMID- 27194609 TI - Transition from NICU to Home: Are the Parents Ready to Manage Any Emergency? An Evidence-Based Project. AB - Transitioning the care of a previously critically ill infant to home poses many challenges for the parents. Prior to the infant's discharge, the parents undergo rigorous training to continue the care of their infants at home. Even after training, parents may feel overwhelmed by the thought of managing an emergency at home. This evidence-based practice project aims to provide parents with additional hands-on practice of cardiopulmonary resuscitation (CPR) prior to their infant's discharge. Based on this project, a program of teaching CPR regularly is established currently in the NICU at Nemours Alfred I. duPont Hospital for Children. PMID- 27194610 TI - Development of the Gastrointestinal System: An Embryonic and Fetal Review. AB - The embryonic and fetal development of the gastrointestinal (GI) tract is important in understanding the development of many GI disorders. This article will review the GI development and relate it to various defects and disorders seen in the preterm and term infant. PMID- 27194611 TI - Hypoxic-Ischemic Encephalopathy and Serum Magnesium Monitoring and Maintenance. AB - Magnesium plays important roles in many physiologic functions including protein synthesis, bone development, and cell membrane function. There is some evidence to suggest a role for magnesium sulfate as a therapeutic neuroprotective agent along with therapeutic hypothermia in infants with hypoxic-ischemic encephalopathy, but studies are inconclusive. Ischemic insult and hypothermia may both play a role in altered magnesium levels in this population. PMID- 27194612 TI - Idea to Publication: Sharing Your Clinical Innovations. AB - Nurses are actively involved in the development of innovative practice projects and in the development of evidence-based guidelines. But rarely are the ideas of nurses and clinical leaders shared in professional publications. This column discusses the importance of sharing one's work through publication and provides strategies to get started. PMID- 27194613 TI - The NICU Mom Who Rarely Visits and What You Can Do About It. AB - NICU nurses often worry about NICU moms who are not able to visit their babies regularly and rightfully so. The mother is key to not only the baby's ability to survive but also thrive, and spare visits do little to help with the bonding process. This article provides solid tips on increasing the NICU mom's visits using strengths and positives instead of guilt. PMID- 27194614 TI - Continuing Education Course. PMID- 27194615 TI - News of the Academy of Neonatal Nursing. PMID- 27194616 TI - A new jump-landing protocol identifies differences in healthy, coper, and unstable ankles in collegiate athletes. AB - Ankle sprains are the most common injury in sport. With stability being an important risk factor for ankle sprains, a jump-landing protocol that can elicit differences in time-to-stabilisation (TTS) is necessary. The objective of this study was to develop a jump-landing protocol that could identify differences in TTS among healthy, 'coper', and unstable ankles of high-level athletes. 61 Division I collegiate athletes (32 females, 29 males; age: 19.9 +/- 1.2 years; height: 176.6 +/- 9.5 cm; mass: 74.3 +/- 10.8 kg) participated in a jump-landing protocol that utilised sporting movements with preparatory steps and a vertical propulsion of the body in two multi-directional jumps. Utilising the landing on a force plate, ground reaction forces were used to quantify TTS. TTS of the unstable group (1.58 +/- 0.62s) was significantly longer than the healthy (1.19 +/- 0.37s; p = 0.050) and 'coper' (1.13 +/- 0.49s; p = 0.019) groups in the forward hops. In addition, TTS of the lateral hops in the unstable group (1.55 +/ 0.63s) was also significantly longer than the healthy (1.14 +/- 0.37s; p = 0.026) and 'coper' (1.15 +/- 0.39s; p = 0.028) groups. This new jump-landing protocol was able to elicit differences in TTS in high-level athletes that were not found using previous protocols. This new jump-landing protocol could be an effective tool to identify injury risk for high-level athletes. PMID- 27194617 TI - Gene expression characterizes different nutritional strategies among three mixotrophic protists. AB - Mixotrophic protists, i.e. protists that can carry out both phototrophy and heterotrophy, are a group of organisms with a wide range of nutritional strategies. The ecological and biogeochemical importance of these species has recently been recognized. In this study, we investigated and compared the gene expression of three mixotrophic protists, Prymnesium parvum, Dinobyron sp. and Ochromonas sp. under light and dark conditions in the presence of prey using RNA Seq. Gene expression of the obligately phototrophic P. parvum and Dinobryon sp. changed significantly between light and dark treatments, while that of primarily heterotrophic Ochromonas sp. was largely unchanged. Gene expression of P. parvum and Dinobryon sp. shared many similarities, especially in the expression patterns of genes related to reproduction. However, key genes involved in central carbon metabolism and phagotrophy had different expression patterns between these two species, suggesting differences in prey consumption and heterotrophic nutrition in the dark. Transcriptomic data also offered clues to other physiological traits of these organisms such as preference of nitrogen sources and photo-oxidative stress. These results provide potential target genes for further exploration of the mechanisms of mixotrophic physiology and demonstrate the potential usefulness of molecular approaches in characterizing the nutritional modes of mixotrophic protists. PMID- 27194618 TI - Influence of Ambient Odors on Time Perception in a Retrospective Paradigm. AB - Environmental stimuli can influence time perception, including sensory stimulations. Among them, odors are known to modulate emotion, attention, behavior, or performance, but few studies have investigated the possible effects of ambient odors on time perception. Thus, the present study aimed to compare in a retrospective paradigm the time estimation in three conditions, i.e., with phenyl ethyl alcohol as a pleasant odor, pyridine as unpleasant odor, and a control condition without ambient odor. A total of 90 participants (M age = 23 years, 10 months) took part in three different tasks, i.e., an aesthetic classification task, a sensorimotor checking task, and a mathematical operations task. Results showed a better accuracy of the time estimation in odor condition (1) independently of the characteristics of odorants (2) limited to tasks with a low cognitive involvement. These findings are discussed in relation to the possible role of attention and arousal in the modulation of time perception by ambient odors. PMID- 27194619 TI - Activity in the rat olfactory cortex is correlated with behavioral response to odor: a microPET study. AB - How olfactory cortical areas interpret odor maps evoked in the olfactory bulb and translate odor information into behavioral responses is still largely unknown. Indeed, rat olfactory cortices encompass an extensive network located in the ventral part of the brain, thus complicating the use of invasive functional methods. In vivo imaging techniques that were previously developed for brain activation studies in humans have been adapted for use in rodents and facilitate the non-invasive mapping of the whole brain. In this study, we report an initial series of experiments designed to demonstrate that microPET is a powerful tool to investigate the neural processes underlying odor-induced behavioral response in a large-scale olfactory neuronal network. After the intravenous injection of [18F]Fluorodeoxyglucose ([18F]FDG), awake rats were placed in a ventilated Plexiglas cage for 50 min, where odorants were delivered every 3 min for a 10-s duration in a random order. Individual behavioral responses to odor were classified into categories ranging from 1 (head movements associated with a short sniffing period in response to a few stimulations) to 4 (a strong reaction, including rearing, exploring and sustained sniffing activity, to several stimulations). After [18F]FDG uptake, rats were anesthetized to perform a PET scan. This experimental session was repeated 2 weeks later using the same animals without odor stimulation to assess the baseline level of activation in each individual. Two voxel-based statistical analyses (SPM 8) were performed: (1) a two-sample paired t test analysis contrasting baseline versus odor scan and (2) a correlation analysis between voxel FDG activity and behavioral score. As expected, the contrast analysis between baseline and odor session revealed activations in various olfactory cortical areas. Significant increases in glucose metabolism were also observed in other sensory cortical areas involved in whisker movement and in several modules of the cerebellum involved in motor and sensory function. Correlation analysis provided new insight into these results. [18F]FDG uptake was correlated with behavioral response in a large part of the anterior piriform cortex and in some lobules of the cerebellum, in agreement with the previous data showing that both piriform cortex and cerebellar activity in humans can be driven by sniffing activity, which was closely related to the high behavioral scores observed in our experiment. The present data demonstrate that microPET imaging offers an original perspective for rat behavioral neuroimaging. PMID- 27194620 TI - German insurers call for central database of complaints against doctors. PMID- 27194621 TI - Endocytosis of indium-tin-oxide nanoparticles by macrophages provokes pyroptosis requiring NLRP3-ASC-Caspase1 axis that can be prevented by mesenchymal stem cells. AB - The biological effects of indium-tin-oxide (ITO) are of considerable importance because workers exposed to indium compounds have been diagnosed with interstitial lung disease or pulmonary alveolar proteinosis; however, the pathophysiology of these diseases is undefined. Here, mice intraperitoneally inoculated with ITO nanoparticles (ITO-NPs) resulted in peritonitis dependent in NLRP3 inflammasome, with neutrophils recruitment and interleukin-1beta (IL-1beta) production. Withal peritoneal macrophages exposed ex vivo to ITO-NPs caused IL-1beta secretion and cytolysis. Further, alveolar macrophages exposed to ITO-NPs in vitro showed ITO NP endocytosis and production of tumor necrosis factor-alpha (TNF-alpha) and IL 1beta, ensued cell death by cytolysis. This cell death was RIPK1-independent but caspase1-dependent, and thus identified as pyroptosis. Endocytosis of ITO-NPs by activated THP-1 cells induced pyroptosis with IL-1beta/TNF-alpha production and cytolysis, but not in activated THP-1 cells with knockdown of NLRP3, ASC, or caspase1. However, exposing activated THP-1 cells with NLRP3 or ASC knockdown to ITO-NPs resulted in cell death but without cytolysis, with deficiency in IL 1beta/TNF-alpha, and revealing features of apoptosis. While, mesenchymal stem cells (MSCs) co-cultured with macrophages impaired both inflammation and cell death induced by ITO-NPs. Together, our findings provide crucial insights to the pathophysiology of respiratory diseases caused by ITO particles, and identify MSCs as a potent therapeutic. PMID- 27194622 TI - Influence of cut-off value on prevalence of short cervical length. AB - OBJECTIVE: To assess the distribution of cervical length (CL) in a large cohort of asymptomatic low-risk women with singleton pregnancy and no previous preterm birth and to explain the low prevalence of short CL <= 30 mm in this cohort. METHODS: This was a secondary analysis of a multicenter cohort study with an embedded randomized controlled trial (Triple P trial; NTR-2078) on the prevention of preterm birth with progesterone. In the cohort study, CL was measured in asymptomatic low-risk women with singleton pregnancy to investigate its predictive capacity to identify those at increased risk for preterm birth. A short CL was defined by a cut-off value of <= 30 mm, based on existing literature. Women with a short CL were subsequently included in a randomized controlled trial evaluating the effect of progesterone, compared with placebo, on preterm birth. In total, 57 centers and 20 234 women participated in the study. Normal distributions for CL were simulated based on the mean and SD of the original data. The distribution of CL was assessed for each individual center and measurements were compared between levels of care: primary (29 ultrasound centers), secondary (21 general hospitals) and tertiary (seven university medical centers) care institutions. Comparison was also performed between centers with low, intermediate and high volume of CL measurements. CL distributions before (n = 12 284 women) and after (n = 7950 women) a national symposium, at which the prevalence of short CL measurements was addressed publicly, were analyzed. RESULTS: Between November 2009 and August 2013, 20 234 women had CL measurements, of whom 367 (1.8%) had a short CL. Mean +/- SD CL was 44.2 +/- 7.8 mm. A 'dip' in the distribution of CL measurements between 20 and 30 mm was observed, defined by a ratio of < 50% when comparing the number of measurements in observed and simulated normal distributions. The dip was present in 89% of participating centers. All centers showed a dip in the distribution of measurements <= 30 mm when analyzed according to the level of care and volume of measurements. A significant difference was found when comparing the distribution before and after publicly addressing the low prevalence of short CL (1.7% vs 2.0% of measurements were <= 30 mm, respectively; P < 0.001). CONCLUSIONS: A cut-off value of 30 mm for CL was used to include women in a randomized clinical trial that was embedded in a cohort study. We suggest that the use of a predefined cut-off value for a short cervix influences the distribution of the CL measurements. Since the measurement is not blinded, preference of assessors for the control or intervention arms may have introduced selection bias. This might have resulted in fewer measurements around the cut-off value. Other trials using similar designs could benefit from this observation and take precautions to avoid selection bias. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 27194625 TI - Sexy again: the renaissance of neutrophils in psoriasis. AB - Notwithstanding their prominent presence in psoriatic skin, the functional role of neutrophilic granulocytes still remains somewhat enigmatic. Sparked by exciting scientific discoveries regarding neutrophil functions within the last years, the interest in these short-lived cells of the innate immune system has been boosted recently. While it had been known for some time that neutrophils produce and respond to a number of inflammatory mediators, recent research has linked neutrophils with the pathogenic functions of IL-17, possibly in conjunction with the formation of NETs (neutrophil extracellular traps). Antipsoriatic therapies exert their effects, at least in part, through interference with neutrophils. Neutrophils also appear to connect psoriasis with comorbid diseases. However, directly tampering with neutrophil functions is not trivial as evinced by the failure of therapeutic approaches targeting redundantly regulated cellular communication networks. It has also become apparent that neutrophils link important pathogenic functions of the innate and the adaptive immune system and that they are intricately involved in regulatory networks underlying the pathophysiology of psoriasis. In order to advocate intensified research into the role of this interesting cell population, we here highlight some features of neutrophils and put them into perspective with our current view of the pathophysiology of psoriasis. PMID- 27194626 TI - The effect of antagonist tooth contact on the biomechanical response of custom fitted mouthguards. AB - BACKGROUND/AIM: Custom-fitted mouthguards are devices used to prevent dental injuries. The aim of this study was to verify the influence of the antagonist contact on the stresses and strains of the anterior teeth, shock absorption and displacement of EVA custom-fitted mouthguards during a horizontal impact. MATERIALS AND METHODS: Finite element models of human maxillary central incisors with and without a mouthguard for different occlusion conditions (with and without antagonist contact) were created based on tomography. A nonlinear dynamic impact analysis using the single-step Houbolt method was performed in which a rigid object hit the model at 1 m s-1 . Strain and stress were evaluated by means of Von Mises and Critical modified Von Mises criterion and shock absorption during impact were calculated as well as the mouthguard displacement. RESULTS: The model without mouthguard and without antagonist contact showed the highest stress and strain values at the enamel and dentin in the tooth crown on impact compared to the model without mouthguard and with antagonist contact. Mouthguard presence reduced the stress and strain values regardless of the occlusion condition. The mouthguard displacement decreased with the mandibular antagonist contact. CONCLUSIONS: Mouthguards are efficient at decreasing the stress and strain values on the tooth in front of an impact reaching more than 90% of shock absorption. A mouthguard with balanced occlusion and maximum number of contacts with mandibular anterior teeth should be considered because it reduces mouthguard displacement. PMID- 27194627 TI - NHS and public health reorganization in England: health protection and emergency planning, preparedness and response perspective. PMID- 27194628 TI - Learning Problems in Children of Refugee Background: A Systematic Review. AB - CONTEXT: Learning problems are common, affecting up to 1 in 10 children. Refugee children may have cumulative risk for educational disadvantage, but there is limited information on learning in this population. OBJECTIVE: To review the evidence on educational outcomes and learning problems in refugee children and to describe their major risk and resource factors. DATA SOURCES: Medline, Embase, PubMed, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, and Education Resources Information Center. STUDY SELECTION: English-language articles addressing the prevalence and determinants of learning problems in refugee children. DATA EXTRACTION: Data were extracted and analyzed according to Arksey and O'Malley's descriptive analytical method for scoping studies. RESULTS: Thirty-four studies were included. Refugee youth had similar secondary school outcomes to their native-born peers; there were no data on preschool or primary school outcomes. There were limited prevalence data on learning problems, with single studies informing most estimates and no studies examining specific language disorders or autism spectrum disorders. Major risk factors for learning problems included parental misunderstandings about educational styles and expectations, teacher stereotyping and low expectations, bullying and racial discrimination, premigration and postmigration trauma, and forced detention. Major resource factors for success included high academic and life ambition, "gift-and-sacrifice" motivational narratives, parental involvement in education, family cohesion and supportive home environment, accurate educational assessment and grade placement, teacher understanding of linguistic and cultural heritage, culturally appropriate school transition, supportive peer relationships, and successful acculturation. LIMITATIONS: Studies are not generalizable to other cohorts. CONCLUSIONS: This review provides a summary of published prevalence estimates for learning problems in resettled refugee children, highlights key risk and resource factors, and identifies gaps in research. PMID- 27194629 TI - Rooming-In to Treat Neonatal Abstinence Syndrome: Improved Family-Centered Care at Lower Cost. AB - BACKGROUND AND OBJECTIVE: The incidence and associated costs of neonatal abstinence syndrome (NAS) have recently risen sharply; newborns with NAS occupy 4% of NICU beds. We implemented a coordinated program for NAS including standardized protocols for scoring, medications and weaning, and a calm rooming in environment, to improve family-centered care and to decrease both length of stay (LOS) and hospital costs. METHODS: In early 2013, a multidisciplinary quality improvement team began consecutive plan-do-study-act (PDSA) cycles. We trained nurses in modified Finnegan scoring, ensured scoring only after on-demand feeds during skin-to-skin care, and standardized physician score interpretation. We provided prenatal family education, increased family involvement in symptom monitoring and nonpharmacologic treatment, and treated otherwise healthy infants on the inpatient pediatric unit instead of in the NICU. We measured outcomes using statistical process control methods. RESULTS: At baseline, 46% of inborn infants at-risk for NAS were treated with morphine; by 2015, this decreased to 27%. Adjunctive use of phenobarbital decreased from 13% to 2% in the same period. Average LOS for morphine-treated newborns decreased from 16.9 to 12.3 days, average hospital costs per treated infant decreased from $19 737 to $8755, and costs per at-risk infant dropped from $11 000 to $5300. Cumulative morphine dose decreased from 13.7 to 6.6 mg per treated newborn. There were no adverse events, and 30-day readmission rates remained stable. CONCLUSIONS: A coordinated, standardized NAS program safely reduced pharmacologic therapy, LOS, and hospital costs. Rooming-in with family and decreased use of NICU beds were central to achieved outcomes. PMID- 27194630 TI - Cardiac troponin T is necessary for normal development in the embryonic chick heart. AB - The heart is the first functioning organ to develop during embryogenesis. The formation of the heart is a tightly regulated and complex process, and alterations to its development can result in congenital heart defects. Mutations in sarcomeric proteins, such as alpha myosin heavy chain and cardiac alpha actin, have now been associated with congenital heart defects in humans, often with atrial septal defects. However, cardiac troponin T (cTNT encoded by gene TNNT2) has not. Using gene-specific antisense oligonucleotides, we have investigated the role of cTNT in chick cardiogenesis. TNNT2 is expressed throughout heart development and in the postnatal heart. TNNT2-morpholino treatment resulted in abnormal atrial septal growth and a reduction in the number of trabeculae in the developing primitive ventricular chamber. External analysis revealed the development of diverticula from the ventricular myocardial wall which showed no evidence of fibrosis and still retained a myocardial phenotype. Sarcomeric assembly appeared normal in these treated hearts. In humans, congenital ventricular diverticulum is a rare condition, which has not yet been genetically associated. However, abnormal haemodynamics is known to cause structural defects in the heart. Further, structural defects, including atrial septal defects and congenital diverticula, have previously been associated with conduction anomalies. Therefore, to provide mechanistic insights into the effect that cTNT knockdown has on the developing heart, quantitative PCR was performed to determine the expression of the shear stress responsive gene NOS3 and the conduction gene TBX3. Both genes were differentially expressed compared to controls. Therefore, a reduction in cTNT in the developing heart results in abnormal atrial septal formation and aberrant ventricular morphogenesis. We hypothesize that alterations to the haemodynamics, indicated by differential NOS3 expression, causes these abnormalities in growth in cTNT knockdown hearts. In addition, the muscular diverticula reported here suggest a novel role for mutations of structural sarcomeric proteins in the pathogenesis of congenital cardiac diverticula. From these studies, we suggest TNNT2 is a gene worthy of screening for those with a congenital heart defect, particularly atrial septal defects and ventricular diverticula. PMID- 27194633 TI - Novice Nurse Practitioner Workforce Transition Into Primary Care: A Literature Review. AB - The purpose of this integrative review was to analyze the current state of the science related to the novice nurse practitioner (NP) transition into primary care. A systematic review of the literature was conducted using the databases Pubmed, MEDLINE, Ovid, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) with the terms nurse practitioner, role, and transition to search articles published after 1997. Three major themes emerged from the literature related to the novice NP transition into primary care. These themes were categorized as "experiencing role ambiguity," "quality of professional and interpersonal relationships," and "facing intrinsic and extrinsic obstacles." Strategies to reduce role ambiguity, improve the quality of professional relationships, and mitigate extrinsic obstacles faced by novice NPs may improve their transition into the primary care workforce. Educational institutions, employers, and novice NPs all have a stake in the successful transition from student to primary care practitioner and should be engaged in developing effective NP transition-to-practice programs. PMID- 27194632 TI - The LAW index as an accurate indicator of the initiation of antiviral treatment in patients with chronic hepatitis B. AB - BACKGROUND AND AIM: Considering that inflammation and fibrosis are major factors for the indication of antiviral treatment, liver stiffness measurements could help identify patients who require antiviral treatment. This study evaluated factors that best identify patients who require antiviral treatment and to develop a new indicator for chronic hepatitis B (CHB). METHODS: Patients with CHB were randomly classified into a training or validation group, and a model for predicting necroinflammatory activity >= A3 or fibrosis grade >= F2 (A3F2) was established in the training group using binary regression analysis and validated in the validation group. Predictive efficacy was compared using area under the receiver-operating characteristics curve analysis. RESULTS: Four-hundred ninety two patients were enrolled. In the training group, female sex, aspartate aminotransferase-to-platelet count ratio index (APRI), and liver stiffness were independent predictors of A3F2 on multivariate analysis. These variables were used to construct a novel model, called the LAW (liver stiffness, APRI, woman) index, as follows: 1.5 * liver stiffness value (kPa) + 3.9 * APRI + 3.2 if female. The LAW index was a better predictor of A3F2 than the APRI or liver stiffness measurement in both training group (0.870; 95% confidence interval, 0.822-0.910) and validation group (0.862; 95% confidence interval, 0.813-0.903). CONCLUSIONS: The LAW index was able to accurately identify patients with CHB who required antiviral treatment. A LAW index of >10.1 could be a strong indicator for the initiation of antiviral treatment in patients with CHB. PMID- 27194631 TI - Effect of salivary agglutination on oral streptococcal clearance by human polymorphonuclear neutrophil granulocytes. AB - Salivary agglutination is an important host defense mechanism to aggregate oral commensal bacteria as well as invading pathogens. Saliva flow and subsequent swallowing more easily clear aggregated bacteria compared with single cells. Phagocytic clearance of bacteria through polymorphonuclear neutrophil granulocytes also seems to increase to a certain extent with the size of bacterial aggregates. To determine a connection between salivary agglutination and the host innate immune response by phagocytosis, an in vitro agglutination assay was developed reproducing the average size of salivary bacterial aggregates. Using the oral commensal Streptococcus gordonii as a model organism, the effect of salivary agglutination on phagocytic clearance through polymorphonuclear neutrophil granulocytes was investigated. Here we describe how salivary aggregates of S. gordonii are readily cleared through phagocytosis, whereas single bacterial cells showed a significant delay in being phagocytosed and killed. Furthermore, before phagocytosis the polymorphonuclear neutrophil granulocytes were able to induce a specific de-aggregation, which was dependent on serine protease activity. The data presented suggest that salivary agglutination of bacterial cells leads to an ideal size for recognition by polymorphonuclear neutrophil granulocytes. As a first line of defense, these phagocytic cells are able to recognize the aggregates and de-aggregate them via serine proteases to a more manageable size for efficient phagocytosis and subsequent killing in the phagolysosome. This observed mechanism not only prevents the rapid spreading of oral bacterial cells while entering the bloodstream but would also avoid degranulation of involved polymorphonuclear neutrophil granulocytes, so preventing collateral damage to nearby tissue. PMID- 27194634 TI - Barriers and Promoters to Participation in the Era of Shared Treatment Decision Making. AB - This study aimed to identify the barriers and promoters for participation in cancer treatment decision in the era of shared decision-making (SDM) process. A qualitative design was utilized. Nineteen nurses and 11 nurse practitioners from oncology inpatient and outpatient settings participated in semi-structured interviews. Data were analyzed using directed content analysis. The findings include practice barrier, patient barrier, institutional policy barrier, professional barrier, scope of practice barrier, insurance coverage barrier, and administrative barrier. Multidisciplinary team approach, having a nursing voice during SDM, high level of knowledge of the disease and treatment, and personal valuation of SDM participation were perceived as promoters. Oncology nurses and nurse practitioners face many barriers to their participation during SDM. Organizational support and system-wide culture of SDM are essential to achieve better cancer treatment decisions outcome. Additional studies are needed to determine the factors that can promote more participation among nurses and nurse practitioners. PMID- 27194635 TI - Transverse lie with prolapsed arm in a female red-howler monkey (Alouatta guariba clamitans - Cabrera, 1940). AB - This study focuses on a case of a red-howler monkey (Alouatta guariba clamitans) which was found with a fetus in a transverse lie position with a prolapsed arm. The topic of this research is well justified as there are no data on this condition involving this type of non-human primate in literature. In this study, a red-howler monkey was observed by locals pulling at her pelvic region for 3 days near a farm. On the third day, the monkey was found lying on the ground at which point she offered no resistance when approached. The environmental police took the monkey to receive medical attention. During the physical examination, it was quickly observed that the monkey was pregnant; the right forelimb of the fetus was exposed from the vulva. An ultrasound revealed a non-viable fetus, and due to the severe weakness of the mother, we opted for euthanasia. During the necropsy, not only was the fetus found macerated but it was also in a transverse lie position with a prolapsed arm and presented no external or internal injuries consistent with trauma. PMID- 27194637 TI - Preliminary survey of local bacteriophages with lytic activity against multi-drug resistant bacteria. AB - Bacteriophages (phages) represent a potential alternative for combating multi drug resistant bacteria. Because of their narrow host range and the ever emergence of novel pathogen variants the continued search for phages is a prerequisite for optimal treatment of bacterial infections. Here we performed an ad hoc survey in the surroundings of a University hospital for the presence of phages with therapeutic potential. To this end, 16 aquatic samples of different origins and locations were tested simultaneously for the presence of phages with lytic activity against five current, but distinct strains each from the ESKAPE group (i.e., Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter cloacae). Phages could be isolated for 70% of strains, covering all bacterial species except S. aureus. Apart from samples from two lakes, freshwater samples were largely devoid of phages. By contrast, one liter of hospital effluent collected at a single time point already contained phages active against two-thirds of tested strains. In conclusion, phages with lytic activity against nosocomial pathogens are unevenly distributed across environments with the prime source being the immediate hospital vicinity. PMID- 27194636 TI - CLOCK promotes 3T3-L1 cell proliferation via Wnt signaling. AB - Circadian genes control most of the physiological functions including cell cycle. Cell proliferation is a critical factor in the differentiation of progenitor cells. However, the role of Clock gene in the regulation of cell cycle via wingless-type (Wnt) pathway and the relationship between Clock and adipogenesis are unclear. We found that the circadian locomotor output cycles kaput (Clock) regulated the proliferation and the adipogenesis of 3T3-L1 preadipocytes. We found that Clock attenuation inhibited the viability of 3T3-L1 preadipocytes in the cell counting kit 8. The expression of c-Myc and Cyclin D1 decreased dramatically in 3T3-L1 when Clock was silenced with short interfering RNA and was also decreased in fat tissue and adipose tissue-derived stem cells of Clock(Delta19) mice. Clock directly controls the expression of the components of Wnt signal transduction pathway, which was verified by serum shock, chromatin immunoprecipitation, Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR). Furthermore, IWR-1, a Wnt signal pathway inhibitor, inhibited the cell cycle promotion by CLOCK, which was detected by cell viability assay, flow cytometry, and qRT-PCR. Therefore, CLOCK transcription control of Wnt signaling promotes cell cycle progression in 3T3-L1 preadipocytes. Clock inhibited the adipogenesis on day 2 in 3T3-L1 cells via Oil Red O staining and qRT-PCR detection and probably related to cellular differentiation. These data provide evidence that the circadian gene Clock regulates the proliferation of preadipocytes and affects adipogenesis. (c) 2016 IUBMB Life, 68(7):557-568, 2016. PMID- 27194640 TI - Multiplexed neural recording along a single optical fiber via optical reflectometry. AB - We introduce the design and theoretical analysis of a fiber-optic architecture for neural recording without contrast agents, which transduces neural electrical signals into a multiplexed optical readout. Our sensor design is inspired by electro-optic modulators, which modulate the refractive index of a waveguide by applying a voltage across an electro-optic core material. We estimate that this design would allow recording of the activities of individual neurons located at points along a 10-cm length of optical fiber with 40-MUm axial resolution and sensitivity down to 100 MUV using commercially available optical reflectometers as readout devices. Neural recording sites detect a potential difference against a reference and apply this potential to a capacitor. The waveguide serves as one of the plates of the capacitor, so charge accumulation across the capacitor results in an optical effect. A key concept of the design is that the sensitivity can be improved by increasing the capacitance. To maximize the capacitance, we utilize a microscopic layer of material with high relative permittivity. If suitable materials can be found-possessing high capacitance per unit area as well as favorable properties with respect to toxicity, optical attenuation, ohmic junctions, and surface capacitance-then such sensing fibers could, in principle, be scaled down to few-micron cross-sections for minimally invasive neural interfacing. We study these material requirements and propose potential material choices. Custom-designed multimaterial optical fibers, probed using a reflectometric readout, may, therefore, provide a powerful platform for neural sensing. PMID- 27194639 TI - Facile Preparation of Bright-Fluorescent Soft Materials from Small Organic Molecules. AB - Highly fluorescent and biocompatible soft materials are desirable for many potential applications, but their synthetic processes are somehow complicated. Herein, we have explored the feasibility of synthesis of unconventional fluorescence soft materials from small organic molecules under mild conditions. A new blue-fluorescent soft material with high quantum yield (89.6 %) and eutectic feature prepared by simple heat treatment of citric acid (CA) and cysteine (Cys) aqueous mixtures below 100 degrees C in air was reported. The as-prepared fluorescent material has the features of facile preparation, low cost, scalable production and easy to process, making it suitable for applications like fluorescent labeling and light-emitting devices. This new finding opens a new venue for the preparation of fluorescent soft materials. PMID- 27194638 TI - Stress reticulocytes lose transferrin receptors by an extrinsic process involving spleen and macrophages. AB - As they mature into erythrocytes during normal erythropoiesis, reticulocytes lose surface transferrin receptors before or concurrently with reticulin. Exosome release accounts for most of the loss of transferrin receptors from reticulocytes. During erythropoietic stress, reticulocytes are released early from hematopoietic tissues and have increased reticulin staining and transferrin receptors. Flow cytometry of dually stained erythrocytes of mice recovering from phlebotomy demonstrated delayed loss of reticulin and transferrin receptors during in vitro maturation compared to in vivo maturation, indicating that an in vivo process extrinsic to the reticulocytes facilitates their maturation. Splenectomy or macrophage depletion by liposomal clodronate inhibited in vivo maturation of reticulocytes and increased the numbers of reticulin-negative, transferrin receptor-positive cells during and after recovery from phlebotomy. This reticulin-negative, transferrin receptor-positive population was rarely found in normal mice. Transmission electron microscopy demonstrated that the reticulin-negative, transferrin receptor-positive cells were elongated and discoid erythrocytes, but they had intracellular and surface structures that appeared to be partially degraded organelles. The results indicate that maturation of circulating stress reticulocytes is enhanced by an extrinsic process that occurs in the spleen and involves macrophage activity. Complete loss of reticulin with incomplete loss of surface transferrin receptors in this process produces a reticulin-negative, transferrin receptor-positive erythrocyte population that has potential utility for detecting prior erythropoietic stresses including bleeding, hemolysis and erythropoietin administration, even after recovery has been completed. Am. J. Hematol. 91:875-882, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27194641 TI - Hospitalization costs and complications in hospitalized patients with type 2 diabetes mellitus in Beijing, China. AB - BACKGROUND: The aim of the present study was to investigate hospitalization costs, diabetes complications, and their relationships using a large dataset in Beijing, China. METHODS: Data for 2006-10 from the 38 top-ranked (Grade 3 A) hospitals in Beijing, obtained from electronic Hospitalization Summary Reports (HSRs), were analyzed for hospitalization costs and diabetic complications. Patient demographics, types of costs, and length of hospital stay (LOS) were also evaluated. RESULTS: During the period evaluated, 62 523 patients with diabetes were hospitalized, of which 41 875 (67.0 %) had diabetes-associated complications. The median cost of hospitalization for diabetic patients was 7996.11 RMB. Prescribed drugs and laboratory tests were two major contributors to hospitalization costs, accounting for 36.2 % and 22.4 %, respectively. Hospitalization costs were significantly associated with LOS, number of complications, age, year of admission, admission status, sex, and medical insurance (P < 0.001). Both hospitalization costs and LOS increased substantially with an increase in the number of complications (P < 0.001). The highest hospitalization costs were seen in those diabetic patients with foot complications. CONCLUSION: Diabetic complications have a significant effect on increases in hospitalization costs and LOS in patients with type 2 diabetes mellitus. PMID- 27194642 TI - Heart Rate-Corrected QT and JT Intervals in Electrocardiograms in Physically Fit Students and Student Athletes. AB - In literature, data on the prevalence of prolonged and shortened corrected QT (QTc) have shown considerable variability. The aim of the study was to compare QTc and JTc intervals of competitive student athletes and noncompetitive sport participants to QTc cutoff points used in athletes. A group of 485 physically fit candidates for the study of kinesiology (139 female and 346 male candidates) aged 18-20 participated in the study. Basic anthropometry, field fitness test, cardiovascular, electrocardiograms measurements, and blood sampling for lipid profile were conducted. The prolonged QTc according to European Society of Cardiology criteria was found in 2.9% of female and 4.3% of male students. When the "Seattle criteria" were used, the proportion of prolonged QTc was 1.44% in female and 0.29% in male students. The shortened QTc according to the Seattle cutoff points was presented in 0.7% of female and 2.0% of male students. The JTc over 400 ms was found in 0.72% of female and 0.29% of male students. The JTc shorter than 320 ms was presented in 0.7% of female and 1.1% of male students. No significant differences were found between students involved in competitive sport and those involved in recreational sporting activities. Female students had lower body mass index and blood pressure values, better blood lipid profile, and lower uric acid concentrations. In conclusion, the Seattle criteria markedly decreased the proportion of prolonged QTc in student athletes, particularly in male students. It seems that the JTc interval could be a better parameter than the QTc interval for the estimation of specific repolarization time in physically fit university students. PMID- 27194643 TI - Influence of nucleobase stoichiometry on the self-assembly of ABC triblock copolymers. AB - ABC triblock copolymers bearing adenine- and thymine-functionalized external blocks self-assembled into long-range, ordered lamellar microphase-separated morphologies on non-patterned substrates. Intermolecular hydrogen bonding formed thymine-adenine triplets and promoted self-assembly into well-defined lamellae consisting of poly(n-butyl acrylate) soft domains and complementary nucleobase hard domains, while thymine-adenine duplets contributed to superior mechanical properties. PMID- 27194644 TI - Ablative non-sequential fractional ultrapulsed CO2 laser pretreatment improves conventional photodynamic therapy with methyl aminolevulinate in a novel human in vitro 3D actinic keratosis skin model. PMID- 27194645 TI - Picture This: Exploring the Lived Experience of High-Functioning Stroke Survivors Using Photovoice. AB - An increasing number of high-functioning stroke survivors are present with minimal functional impairments and are often discharged with reduced access to community reintegration. Our objectives were to explore the lived experience of high-functioning stroke survivors and to identify gaps in community and rehabilitation services. Photovoice was used with five high-functioning stroke survivors to photo-document their experiences. A modified inductive thematic analysis was used, and meanings behind the photographs were elicited through four focus group sessions followed by photography exhibitions. Five themes emerged: lack of understanding and consideration for persons with disability, emotional and behavioral impacts after stroke, self-reliance and dependence on others, importance of appropriate and accessible services, and financial determinants of quality of life. By including service users' voices; investing in adapted, community-based programs; and providing educational programs for creating attitudinal change among service providers, the polarization between who can and cannot access services will be reduced. PMID- 27194646 TI - Sixty seconds on . . . psilocybin. PMID- 27194647 TI - Fluorescent liquid pyrene derivative-in-water microemulsions. AB - A fluorescent liquid pyrene derivative with a high fluorescence quantum yield (65%) in the bulk state is reported. With this as the sole oil phase, stable luminescent oil-in-water microemulsions have been prepared. Increasing the loading of liquid pyrene swells the droplets, as detected by small-angle neutron scattering. These larger droplets have a greater proportion of pyrene excimer emission contribution in their photoluminescence spectra, which leads to a red shift in the chromaticity of the emission. PMID- 27194649 TI - To thine own self be true? Clarifying the effects of identity discrepancies on psychological distress and emotions. AB - After many years of research across disciplines, it remains unclear whether people are more motivated to seek appraisals that accurately match self-views (self-verification) or are as favorable as possible (self-enhancement). Within sociology, mixed findings in identity theory have fueled the debate. A problem here is that a commonly employed statistical approach does not take into account the direction of a discrepancy between how we see ourselves and how we think others see us in terms of a given identity, yet doing so is critical for determining which self-motive is at play. We offer a test of three competing models of identity processes, including a new "mixed motivations" model where self-verification and self-enhancement operate simultaneously. We compare the models using the conventional statistical approach versus response surface analysis. The latter method allows us to determine whether identity discrepancies involving over-evaluation are as distressing as those involving under-evaluation. We use nationally representative data and compare results across four different identities and multiple outcomes. The two statistical approaches lead to the same conclusions more often than not and mostly support identity theory and its assumption that people seek self-verification. However, response surface tests reveal patterns that are mistaken as evidence of self-verification by conventional procedures, especially for the spouse identity. We also find that identity discrepancies have different effects on distress and self-conscious emotions (guilt and shame). Our findings have implications not only for research on self and identity across disciplines, but also for many other areas of research that incorporate these concepts and/or use difference scores as explanatory variables. PMID- 27194648 TI - Happiness and Identities. AB - Previous sociological research has focused on macro forces that are associated with overall happiness with one's life, but it has neglected an analysis of happiness in immediate situations and the micro forces that may shape it. In this study, we examine social structural as well as individual factors that may influence happiness in situations that are morally challenging. Data are examined from an experiment in which satisfying self-interests may involve cheating to get ahead. The results reveal that while distal, structural factors influence happiness for those who do not cheat, proximal, individual factors influence happiness for those who cheat. We discuss how both macro and micro forces may shape happiness in situations. PMID- 27194650 TI - Moral opinion polarization and the erosion of trust. AB - Since Puntam's seminal work on declining levels of social capital, the question of how social trust is formed has reached unprecedented heights of critical enquiry. While most of the current research concentrates on ethnic diversity and income inequality as the main influences driving down generalized trust, we focus on opinion polarization as another potential impact factor on trust. In more detail, we investigate the extent to which polarization over morally charged issues such as homsexuality, abortion and euthanasia affects individuals' likelihood to trust others. We hypothesize that moral issues have a natural tendency to divide societies' opinions into opposing poles and, thus, to challenge social cohesion in modern civil societies. Based on hierarchical analyses of the fifth wave of the World Values Survey (WVS) - comprising a sample of 39 countries - our results reveal that individuals living in countries characterized by more opinion polarization tend to have less trust in other people. PMID- 27194651 TI - The consequences of parental labor migration in China for children's emotional wellbeing. AB - Using data from the 2010 wave of the China Family Panel Studies (CFPS), we study the effects of internal migration in China on the emotional wellbeing of children age 10-15. The 2010 CFPS, a national probability sample survey of the Chinese population, includes 3464 children within this age range. We compare five groups: rural children with local registration living with both parents; urban children with local registration living with both parents; children accompanying their migrant parent(s), children left behind with one parent when the other parent goes out to work; and children left behind or sent to live with others when both parents go out to work. We expect the last three groups to be at risk of increased emotional difficulties compared to children living with both parents. We test these expectations using both conventional regression models and community fixed-effects models. The evidence supporting our expectations is very weak and inconsistent, leading us to conclude that in the Chinese context family arrangements have little impact on the emotional wellbeing of children. We conclude by offering some conjectures as to why this is so. PMID- 27194652 TI - Universalism, conservation and attitudes toward minority groups. AB - Findings from previous studies corroborate the hypothesis that universalism and conservation values are associated with negative attitudes toward immigration. In the current study we examine whether universalism and conservation values also play a critical role in the explanation of attitudes toward other minority groups. Drawing on previous research on group-focused enmity, we explore its relations with universalism and conservation values in a German sample. Employing structural equation modeling, we find that individuals who prioritize universalism values approve of various minorities more whereas those who prioritize conservation values exhibit more disapproval. PMID- 27194653 TI - Inter-generational micro-class mobility during and after socialism: The power, education, autonomy, capital, and horizontal (PEACH) model in Hungary. AB - We propose a theoretical model of how occupational mobility operates differently under socialism than under market regimes. Our model specifies four vertical dimensions of occupational resources-power, education, autonomy, and capital-plus a horizontal dimension consisting of linkages among occupations in the same economic branch. Given the nature of state socialist political-economic institutions, we expect power to exhibit much stronger effects in the socialist mobility regime, while autonomy and capital should play greater stratifying roles after the market transition. Education should have stable effects, and horizontal linkages should diminish in strength with market reforms. We estimate our model's parameters using data from surveys conducted in Hungary during and after the socialist period. We adopt a micro-class approach, though we test it against approaches that use more aggregated class categories. Our model provides a superior fit to other mobility models, and our results confirm our hypotheses about the distinctive features of the state socialist mobility regime. Mobility researchers often look for common patterns characterizing mobility in all industrialized societies. Our findings suggest that national institutions can produce fundamentally distinct patterns of mobility. PMID- 27194654 TI - Does counterterrorist legislation hurt human rights practices? A longitudinal cross-national analysis. AB - In the aftermath of the 9/11 terrorist attacks, many countries have passed new counterterrorist legislation. One of the common assumptions about such legislation is that it comes with a price: a compromise to practices of human rights. Previous research, looking at a wide range of case studies, suggested that this is indeed the case and that counterterrorist legislation often leads to subsequent repression. However, no large-scale cross-national study has yet assessed this relationship. Relying on a newly assembled database on nation-level counterterrorist legislation for the years 1981-2009, we conduct a cross-national time series analysis of legislation and repression. Our analyses find little evidence for a significant relationships between national counterterrorist legislation and various measures of core human rights in most countries. However, while legislation does not affect repression of physical integrity rights in countries with low and high levels of repression, it is associated with greater state repression in countries with intermediate scores of repression. PMID- 27194655 TI - Do scheduled caste and scheduled tribe women legislators mean lower gender-caste gaps in primary schooling in India? AB - Despite India's substantial investments in primary schooling, gaps in schooling persist across gender and caste-with scheduled caste and scheduled tribe (SC/ST) girls being particularly disadvantaged. The representation of SC/ST women in state legislatures may help to mitigate this disadvantage. Specifically, because of her intersecting gender and caste/tribe identities, a SC/ST woman legislator might maintain a strong sense of solidarity especially with SC/ST girls and women, and support legislative policies benefitting SC/ST girls. Consequently, for this reason, we expect that living in a district where SC/ST women represent in state legislatures in a higher proportion may increase SC/ST girls' primary school completion, progression and performance. We tested this hypothesis using district-level data between 2000 and 2004 from the Indian Election Commission, the 2004/5 India Human Development Survey, and the Indian Census of 2001. As expected, the representation of SC/ST women in state legislatures was positively associated with SC/ST girls' grade completion and age-appropriate grade progression but was apparent not SC/ST girls' primary-school performance. SC/ST women's representation in state legislatures may reduce gender-caste gaps in primary-school attainment in India. PMID- 27194656 TI - Measuring students' school context exposures: A trajectory-based approach. AB - Studies of school effects on children's outcomes usually use single time-point measures. I argue that this approach fails to account for (1) age-based variation in children's sensitivity to their surroundings; (2) differential effects stemming from differences in the length of young people's exposures; and (3) moves between contexts and endogenous changes over time within them. To evaluate the merits of this argument, I specify and test a longitudinal model of school effects on children's academic performance. Drawing on recent advances in finite mixture modeling, I identify a series of distinct school context trajectories that extend across a substantial portion of respondents' elementary and secondary school years. I find that these trajectories vary significantly with respect to shape, with some students experiencing significant changes in their environments over time. I then show that students' trajectories of exposure are related to their 8th grade achievement, even after controlling for point-in-time measures of school context. PMID- 27194657 TI - Math-oriented fields of study and the race gap in graduation likelihoods at elite colleges. AB - This study examines the relationship between chosen field of study and the race gap in college completion among students at elite colleges. Fields of study are characterized by varying institutional arrangements, which impact the academic performance of students in higher education. If the effect of fields on graduation likelihoods is unequal across racial groups, then this may account for part of the overall race gap in college completion. Results from a large sample of students attending elite colleges confirm that fields of study influence the graduation likelihoods of all students, above and beyond factors such as students' academic and social backgrounds. This effect, however, is asymmetrical: relative to white students, the negative effect of the institutional arrangements of math-oriented fields on graduation likelihood is greater for black students. Therefore, the race gap is larger within math-oriented fields than in other fields, which contributes to the overall race gap in graduation likelihoods at these selective colleges. These results indicate that a nontrivial share of the race gap in college completion is generated after matriculation, by the environments that students encounter in college. Consequently, policy interventions that target field of study environments can substantially mitigate racial disparities in college graduation rates. PMID- 27194658 TI - Staying in STEM or changing course: Do natives and immigrants pursue the path of least resistance? AB - This paper examines why Science, Technology, Engineering and Math (STEM) fields are becoming "immigrant" fields of study as native students shift from STEM fields to law, medicine and business. Using data from the 2010 National Survey of College Graduates, the analyses find that foreign college-educated immigrants with STEM degrees tend to remain in STEM fields, while natives are more likely to shift from STEM fields to law, medicine and business in graduate school. Among those who moved into law, medicine and business, the gains in earnings are larger for natives than for foreign educated immigrants. These results have important implications for the social mobility of highly educated natives and immigrants. PMID- 27194659 TI - Intermediate peer contexts and educational outcomes: Do the friends of students' friends matter? AB - Sociologists of education have long been interested in the effects of peer relations on educational outcomes. Recent theory and research on adolescence suggest that peers on the boundaries of students' friendship networks may play an important role in shaping behaviors and educational outcomes. In this study, we examine the importance of a key "intermediate peer context" for students' outcomes: the friends of a student's friends. Our findings indicate both friends' and friends' friends' characteristics independently predict students' college expectations and their risk of dropping out of high school (although only friends' characteristics predict GPA). Our models suggest the magnitude of students' friends-of-friends' characteristics are at least as large their friends' characteristics. Together, the association between the peer context and students outcomes is considerably larger when accounting for both the characteristics of students' friends and the friends of their friends. PMID- 27194660 TI - Early cognitive skills of Mexican-origin children: The roles of parental nativity and legal status. AB - Although one-third of children of immigrants have undocumented parents, little is known about their early development. Using data from the Los Angeles Family and Neighborhood Survey and decennial census, we assessed how children's cognitive skills at ages 3 to 5 vary by ethnicity, maternal nativity, and maternal legal status. Specifically, Mexican children of undocumented mothers were contrasted with Mexican children of documented mothers and Mexican, white, and black children with U.S.-born mothers. Mexican children of undocumented mothers had lower emergent reading skills than all other groups and lower emergent mathematics skills than all groups with U.S.-born mothers. Multilevel regression models showed that differences in reading skills are explained by aspects of the home environment, but the neighborhood context also matters. Cross-level interactions suggest that immigrant concentration boosts emergent reading and mathematics skills for children with undocumented parents, but does not similarly benefit children whose parents are native born. PMID- 27194661 TI - Why do Asian Americans academically outperform Whites? - The cultural explanation revisited. AB - We advocate an interactive approach to examining the role of culture and SES in explaining Asian Americans' achievement. We use Education Longitudinal Study (ELS) 2002 baseline data to test our proposition that the cultural orientation of Asian American families is different from that of white American families in ways that mediate the effects of family SES on children's academic achievement. The results support our hypothesis, indicating that: (1) SES's positive effects on achievement are stronger among white students than among Asian-Americans; (2) the association between a family's SES and behaviors and attitudes is weaker among Asian-Americans than among Whites; (3) a fraction of the Asian-White achievement gap can be accounted for by ethnic differences in behaviors and attitudes, particularly ethnic differences in family SES's effects on behaviors and attitudes. We find that Asian Americans' behaviors and attitudes are less influenced by family SES than those of Whites are and that this difference helps generate Asians' premium in achievement. This is especially evident at lower levels of family SES. PMID- 27194663 TI - Urban density and the metabolic reach of metropolitan areas: A panel analysis of per capita transportation emissions at the county-level. AB - We engage a tension in the urban environment literature that positions cities as both drivers of environmental destruction and loci of environmental protection. We argue that the traditional binary view of cities as either harmful or beneficial is too simplistic; we advance a more nuanced understanding of cities to study their internal and external metabolic effects in terms of carbon emissions from on-road transportation at the county-level across the continental United States between 2002 and 2007. First, utilizing satellite imagery from the National Land Cover Database, we create a novel measure of population density by quantifying the number of people per square mile of impervious surface area. Second, we develop a measure of metropolitan adjacency from the rural classifications datasets published by the USDA. In spatial regression models, we find that while higher density reduces emissions, counties that are geographically isolated from metropolitan areas actually have lower per capita emissions, all else equal. We elaborate on the conceptual, methodological, and practical implications of our study in the conclusion. PMID- 27194662 TI - Parental and adolescent health behaviors and pathways to adulthood. AB - This paper examines associations among parental and adolescent health behaviors and pathways to adulthood. Using data from the National Longitudinal Study of Adolescent to Adult Health, we identify a set of latent classes describing pathways into adulthood and examine health-related predictors of these pathways. The identified pathways are consistent with prior research using other sources of data. Results also show that both adolescent and parental health behaviors differentiate pathways. Parental and adolescent smoking are associated with lowered probability of the higher education pathway and higher likelihood of the work and the work & family pathways (entry into the workforce soon after high school completion). Adolescent drinking is positively associated with the work pathway and the higher education pathway, but decreases the likelihood of the work & family pathway. Neither parental nor adolescent obesity are associated with any of the pathways to adulthood. When combined, parental/adolescent smoking and adolescent drinking are associated with displacement from the basic institutions of school, work, and family. PMID- 27194664 TI - Light and shadows: An analysis of racial differences between siblings in Brazil. AB - Using data from the 2010 Census of Brazil, this article quantitatively examines the phenomenon of sibling differences in racial classification. In sum, the findings demonstrate that within-sibling racial heterogeneity occurs in 17-19% of families. The strongest predictor of racial discordance between siblings is racial discordance between parents. Furthermore, within-sibling regression models establish that race exhibits a modest but statistically significant association with some education and labor market outcomes. Most outcomes are not associated with race for siblings aged 15-19, although in families with both sexes, darker females have more favorable educational outcomes, while darker males have less favorable outcomes. In contrast, darker siblings aged 20-25 are less advantaged than their lighter brothers and sisters along a number of dimensions. They have significantly lower education, lower personal income, lower formal employment, and lower occupational status. It is argued that patterns for siblings aged 20-25 may be indicative of individual racial discrimination. PMID- 27194665 TI - American football and national pride: Racial differences. PMID- 27194666 TI - Gangs, clubs, and alcohol: The effect of organizational membership on adolescent drinking behavior. AB - How does adolescent organizational membership in general, and simultaneous membership in distinct types of organizations in particular, impact drinking behavior? While past studies have focused either on the learning effect of involvement with gangs or on the constraining influence of conventional organizations on adolescent problem behavior, we explore the possibility that conventional school clubs can serve as socializing opportunities for existing gang members to engage in drinking behavior with non-gang club members. Using the Add Health data, we show that gang members drink more often, and engage in more binge drinking, than non-members. More importantly, individuals who are members of both gangs and school clubs drink alcohol at greater levels than those who are solely involved in gangs. In addition, non-gang adolescents who are co-members with gang members in the same school club are more likely to drink alcohol than non-members. This result has important implications for understanding the role of organizations in adolescent behavior and suggests that the study of delinquent behaviors would benefit from devoting more attention to individuals who bridge distinct types of organizations. PMID- 27194668 TI - Relationships Between Internal and External Training Load in Team-Sport Athletes: Evidence for an Individualized Approach. AB - PURPOSE: The aim of this study was to quantify and predict relationships between rating of perceived exertion (RPE) and GPS training-load (TL) variables in professional Australian football (AF) players using group and individualized modeling approaches. METHODS: TL data (GPS and RPE) for 41 professional AF players were obtained over a period of 27 wk. A total of 2711 training observations were analyzed with a total of 66 +/- 13 sessions/player (range 39 89). Separate generalized estimating equations (GEEs) and artificial-neural network analyses (ANNs) were conducted to determine the ability to predict RPE from TL variables (ie, session distance, high-speed running [HSR], HSR %, m/min) on a group and individual basis. RESULTS: Prediction error for the individualized ANN (root-mean-square error [RMSE] 1.24 +/- 0.41) was lower than the group ANN (RMSE 1.42 +/- 0.44), individualized GEE (RMSE 1.58 +/- 0.41), and group GEE (RMSE 1.85 +/- 0.49). Both the GEE and ANN models determined session distance as the most important predictor of RPE. Furthermore, importance plots generated from the ANN revealed session distance as most predictive of RPE in 36 of the 41 players, whereas HSR was predictive of RPE in just 3 players and m/min was predictive of RPE in just 2 players. CONCLUSIONS: This study demonstrates that machine learning approaches may outperform more traditional methodologies with respect to predicting athlete responses to TL. These approaches enable further individualization of load monitoring, leading to more accurate training prescription and evaluation. PMID- 27194669 TI - Junior doctors' contract agreement is reached. PMID- 27194670 TI - Evaluation of 99m Tc-resveratrol as a colon cancer targeting probe. AB - The study aimed to evaluate cancer-targeting potential of a newly synthesised radiopharmaceutical, 99m Tc-resveratrol in vivo, using colon cancer model. Colon cancer was induced in 20 male Sprague-Dawley rats by subcutaneous administration of 1,2-dimethylhydrazine (DMH), dissolved in 1 mM EDTA-normal saline, at a dose of 30 mg/kg body weight twice a week for first 4 weeks and once a week for next 12 weeks. A control group containing normal rats was used for result comparison. Colon cancer in DMH-treated group was confirmed by gross analysis of the colon, by histopathological analysis and molecular marker study in tumour tissue. At the end of the treatment period, the animals from the two groups were used for bio distribution evaluation of 99m Tc-resveratrol at different time intervals. High uptake of 99m Tc-resveratrol was recorded in rat liver, spleen and kidneys, and the ratio of colon tumour uptake to normal colon uptake in DMH-treated rats increased significantly (P <= 0.01) with time, to reach a maximum value at 2 h but decreased thereafter. High uptake at the tumour site as compared to normal colon tissue was observed; however, the uptake by cancer cells at the target site was limited by high reticulo-endothelial uptake and rapid metabolism. PMID- 27194667 TI - Sociometric network structure and its association with methamphetamine use norms among homeless youth. AB - Homeless youths' social networks are consistently linked with their substance use. Social networks influence behavior through several mechanisms, especially social norms. This study used sociometric analyses to understand whether social norms of drug use behaviors are clustered in network structures and whether these perceived norms (descriptive and injunctive) influence youths' drug use behaviors. An event-based approach was used to delineate boundaries of the two sociometric networks of homeless youth, one in Los Angeles, CA (n = 160) and the other in Santa Monica, CA (n = 130). Network characteristics included centrality (i.e., popularity) and cohesiveness (location in dense subnetworks). The primary outcome was recent methamphetamine use. Results revealed that both descriptive and injunctive norms influenced methamphetamine use. Network cohesion was found to be associated with perception of both descriptive and injunctive norms in both networks, however in opposite directions. Network interventions therefore might be effective if designed to capitalize on social influence that naturally occurs in cohesive parts of networks. PMID- 27194671 TI - Plasma micoRNA-122 as a predictive marker for treatment response following transarterial chemoembolization in patients with hepatocellular carcinoma. AB - BACKGROUND AND AIM: Circulating microRNA (miR)-122 has recently been investigated as a potential biomarker of various hepatic diseases, such as chronic hepatitis and hepatocellular carcinoma (HCC). We investigated the association between plasma miR-122 levels and the treatment outcomes following transarterial chemoembolization (TACE) in HCC patients. METHODS: We included 177 HCC patients treated with TACE in the study; TACE refractoriness and liver transplantation free survival were evaluated during follow up. Pretreatment plasma miR-122 levels were assessed using quantitative real-time polymerase chain reaction. Relative quantification of miR-122 expression (fold change) was determined using the 2( DeltaDeltaCt) method. MiR-16 was used as an internal control for the normalization of miRNA data. RESULTS: During the mean follow up of 22.4 (range, 1 79) months, 112 (69.5%) patients exhibited TACE refractoriness. Multivariate analyses showed that tumor number (hazard ratio [HR], 2.51; 95% confidence interval [CI], 1.43-4.41; P = 0.001) and tumor size (HR, 2.65; 95% CI, 1.62-4.32; P = 0.000) can independently predict overall TACE refractoriness. High miR-122 expression (> 100) was associated with early TACE refractoriness (within 1 year; HR, 2.77; 95% CI, 1.12-6.86; P = 0.028), together with tumor number (HR, 22.73; 95% CI, 2.74-188.66; P = 0.004) and tumor size (HR, 4.90; 95% CI, 1.99-12.06; P = 0.001). Univariate analyses showed that high miR-122 expression tends to be associated with poor liver transplantation-free survival (HR, 1.42; 95% CI, 0.95 2.11; P = 0.085). However, it was statistically insignificant in multivariate analysis. CONCLUSION: High expression levels of plasma miR-122 are associated with early TACE refractoriness in HCC patients treated with TACE. PMID- 27194672 TI - Appendicitis during pregnancy in a Greenlandic Inuit woman; antibiotic treatment as a bridge-to-surgery in a remote area. AB - Appendicitis during pregnancy causes severe diagnostic problems, and is associated with an increase in perforation rate and morbidity compared to that in the normal population. In addition, it may cause preterm birth and fetal loss. In remote areas, appendicitis during pregnancy, besides presenting diagnostic problems, also creates treatment difficulties. In Northern Greenland, geographical distances are vast, and weather conditions can be extreme. We report a case of a Greenlandic Inuit woman who presented with appendicitis during pregnancy. The nearest hospital with surgical and anaesthetic care was located nearly 1200 km away, and, due to extreme weather conditions, she could not be transferred immediately. She was treated with intravenous antibiotic treatment, and after weather conditions had improved, she was transferred by aeroplane and underwent appendicectomy. She recovered without complications. Our case suggests that appendicitis during pregnancy may be treated with antibiotics in remote areas until surgical treatment is available. PMID- 27194673 TI - Uncommon cause of acute encephalopathy in liver cirrhosis. AB - A 49-year-old woman with a medical history of alcoholic cirrhosis status post transjugular intrahepatic portosystemic shunt (post-TIPS) in 2012, and ongoing alcohol abuse, presented to the hospital, with haematuria. CT intravenous pyelogram (IVP) was normal except for 'a large intrahepatic cystic mass adjacent to the TIPS, causing intrahepatic biliary duct dilation'. The patient also presented with acute encephalopathy, jaundice, right upper quadrant abdominal pain and hyperbilirubinaemia (total bilirubin of 8.1 mg/dL with direct bilirubin of 3.0 mg/dL). She remained encephalopathic despite adequate treatment for alcohol withdrawal, hepatic encephalopathy and enterococcus urinary tract infection. MRI of the abdomen later confirmed presence of an obstructing biloma. The biloma, drained by CT-guided percutaneous drains, demonstrated an Escherichia coli and ESBL Klebsiella infection. The patient's encephalopathy completely resolved after treatment of the infected biloma. With adequate drainage, her hyperbilirubinaemia resolved to her post-TIPS baseline (total bilirubin of 3.7 mg/dL with direct bilirubin of 3.3 mg/dL). PMID- 27194674 TI - Trichoblastic carcinosarcoma: an authentic cutaneous carcinosarcoma. AB - We describe a trichoblastic carcinosarcoma on the forehead of a 65-year-old man. This is the fifth case of trichoblastic carcinosarcoma in the literature and the first to be reported from the USA. It was successfully treated with direct excision. Trichoblastic carcinosarcoma should be distinguished from epidermal carcinosarcoma. We believe trichoblastic carcinosarcoma is an authentic carcinosarcoma derived from multiple progenitor cells whereas epidermal carcinosarcomas are derived from a single progenitor cell that undergoes epithelial to mesenchymal transition, and are better considered as sarcomatoid carcinomas. PMID- 27194675 TI - First reported association of chronic lymphocytic leukaemia and interstitial granulomatous dermatitis. AB - Interstitial granulomatous dermatitis (IGD), a rare disease, is well known to be associated with connective tissue disorders, malignancies and several drugs. We describe this first case of IGD in association with chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL). A 66-year-old woman with a 6-year history of untreated CLL/SLL, presented with a 2-month history of progressively worsening eruption of the left thigh, along with fatigue, lymphadenopathy and night sweats. Skin biopsy showed findings consistent with IGD and infiltration of CLL. The eruption was non-responsive to treatment with antibiotics and local steroids. There was a significant improvement in the rash after an initial cycle of chemotherapy (combination therapy with bendamustine and rituximab) and complete resolution by the third cycle, for the treatment of her CLL. We suggest that the possibility of an underlying haematological malignancy should be investigated in patients with a skin rash non-responsive to conventional therapy. PMID- 27194676 TI - Paraneoplastic cerebellar degeneration as a marker of endometrial cancer recurrence. AB - An 84-year-old woman developed a cerebellar syndrome having undergone a total abdominal hysterectomy and bilateral salpingo-oophorectomy for endometrial cancer 1 year previously. She was found to be anti-Yo antibody positive and was diagnosed with paraneoplastic cerebellar degeneration (PCD). A subsequent positron emission tomography scan and lymph node biopsy identified recurrence of her endometrial cancer. This case illustrates how PCD can be an indicator of cancer recurrence, underlines the significance of PCD as a prompt to search for underlying malignancy, and highlights the difficulties PCD poses to the clinician in terms of diagnosis and management. PMID- 27194677 TI - Multimodality imaging of a paediatric pancreatic fracture. PMID- 27194678 TI - Benign anlage tumour: a very unusual neck mass. AB - A 44-year-old woman presented with a slow-growing asymptomatic neck swelling at the left medial clavicle. Haematological and biochemical work up was normal and an ultrasound confirmed the swelling, but needle aspiration was non-diagnostic. As lymphoma was the main differential diagnosis, the swelling was completely excised. Immunohistochemistry yielded a rare lesion, suspected to represent a myoepithelial/mixed cellularity tumour of soft tissue. The extreme rarity of these tumours required a confirmatory secondary opinion, which ultimately led to it being identified as a benign anlage tumour (previously known as an ectopic hamartomatous thymoma) This case highlights the fact that thorough assessment of patients with neck swellings should be undertaken to rule out sinister causes keeping in mind more rare differentials-helping to guide final management. PMID- 27194679 TI - Long-term therapy-free remission in a patient with platelet-derived growth factor receptor beta-rearranged myeloproliferative neoplasm. PMID- 27194680 TI - Isolated hydatid cyst of the breast that developed after breast feeding. AB - A hydatid cyst of the breast is extremely rare, even in endemic areas. There are few reports of breast hydatid cysts. We report a case of an isolated hydatid cyst of the breast that was identified as a painless breast lump that had increased in size just after completion of breast feeding and was present with a painful breast mass after 25 years. This may indicate the possibility of retrograde passage of an Echinococcus granulosus egg through lactating ducts during breast feeding, liberation of an embryo that penetrates ductal mucus and enters the breast tissue and then develops into a hydatid cyst. When a patient comes from an area with little healthcare and where hydatid cysts are epidemic, and if this disease was indicated by radiologic or serologic examination, total mass excision without spillage is the best diagnostic and treatment. PMID- 27194681 TI - Intracerebral fibroma: a case report and review of the literature. AB - Intracerebral fibromas are among the most rare neoplasms found in the central nervous system. Ten previously reported cases have been documented in the literature including only two reported cases since 1985. As a result, little is known about these uncommon intracerebral fibrous tumors. We report a case of an intracerebral fibroma without dural or leptomeningeal attachment, discuss the pertinent diagnostic findings and briefly review all prior reports of this entity. PMID- 27194682 TI - Mature brain tissue in the sacrococcygeal region. AB - Complete mature brain tissue in sacrococcygeal region is a rare congenital anomaly in a newborn, which usually is misdiagnosed for sacrococcygeal teratoma. Glial tumor-like ependymoma is also common in sacrococcygeal area but mostly appears later in life. We present a case of complete heterotopic brain tissue in the sacrococcygeal region. The patient underwent total excision of mass with coccygectomy. To our knowledge it is the second case being reported. PMID- 27194684 TI - Analysis of Humoral Immune Responses to Surface and Virulence-Associated Chlamydia abortus Proteins in Ovine and Human Abortions by Use of a Newly Developed Line Immunoassay. AB - The obligate intracellular bacterium Chlamydia abortus is the causative agent of enzootic abortion of ewes and poses a significant zoonotic risk for pregnant women. Using proteomic analysis and gene expression library screening in a previous project, we identified potential virulence factors and candidates for serodiagnosis, of which nine were scrutinized here with a strip immunoassay. We have shown that aborting sheep exhibited a strong antibody response to surface (MOMP, MIP, Pmp13G) and virulence-associated (CPAF, TARP, SINC) antigens. While the latter disappeared within 18 weeks following abortion in a majority of the animals, antibodies to surface proteins persisted beyond the duration of the study. In contrast, nonaborting experimentally infected sheep developed mainly antibodies to surface antigens (MOMP, MIP, Pmp13G), all of which did not persist. We were also able to detect antibodies to these surface antigens in C abortus infected women who had undergone septic abortion, whereas a group of shepherds and veterinarians with occupational exposure to C abortus-infected sheep revealed only sporadic immune responses to the antigens selected. The most specific antigen for the serodiagnosis of human C abortus infections was Pmp13G, which showed no cross-reactivity with other chlamydiae infecting humans. We suggest that Pmp13G-based serodiagnosis accomplished by the detection of antibodies to virulence-associated antigens such as CPAF, TARP, and SINC may improve the laboratory diagnosis of human and animal C abortus infections. PMID- 27194683 TI - Standard Genotyping Overestimates Transmission of Mycobacterium tuberculosis among Immigrants in a Low-Incidence Country. AB - Immigrants from regions with a high incidence of tuberculosis (TB) are a risk group for TB in low-incidence countries such as Switzerland. In a previous analysis of a nationwide collection of 520 Mycobacterium tuberculosis isolates from 2000 to 2008, we identified 35 clusters comprising 90 patients based on standard genotyping (24-locus mycobacterial interspersed repetitive-unit-variable number tandem-repeat [MIRU-VNTR] typing and spoligotyping). Here, we used whole genome sequencing (WGS) to revisit these transmission clusters. Genome-based transmission clusters were defined as isolate pairs separated by <=12 single nucleotide polymorphisms (SNPs). WGS confirmed 17/35 (49%) MIRU-VNTR typing clusters; the other 18 clusters contained pairs separated by >12 SNPs. Most transmission clusters (3/4) of Swiss-born patients were confirmed by WGS, as opposed to 25% (4/16) of the clusters involving only foreign-born patients. The overall clustering proportion was 17% (90 patients; 95% confidence interval [CI], 14 to 21%) by standard genotyping but only 8% (43 patients; 95% CI, 6 to 11%) by WGS. The clustering proportion was 17% (67/401; 95% CI, 13 to 21%) by standard genotyping and 7% (26/401; 95% CI, 4 to 9%) by WGS among foreign-born patients and 19% (23/119; 95% CI, 13 to 28%) and 14% (17/119; 95% CI, 9 to 22%), respectively, among Swiss-born patients. Using weighted logistic regression, we found weak evidence of an association between birth origin and transmission (adjusted odds ratio of 2.2 and 95% CI of 0.9 to 5.5 comparing Swiss-born patients to others). In conclusion, standard genotyping overestimated recent TB transmission in Switzerland compared to WGS, particularly among immigrants from regions with a high TB incidence, where genetically closely related strains often predominate. We recommend the use of WGS to identify transmission clusters in settings with a low incidence of TB. PMID- 27194685 TI - Comparison of Virulence Gene Identification, Ribosomal Spacer PCR, and Pulsed Field Gel Electrophoresis for Typing of Staphylococcus aureus Strains Isolated from Cases of Subclinical Bovine Mastitis in the United States. AB - Staphylococcus aureus is one of the most important pathogens causing contagious mastitis in dairy cattle worldwide. The objectives of this study were to determine if recently described S. aureus genotype B was present among previously characterized isolates from cases of bovine intramammary infection in the United States and to compare pulsed-field gel electrophoresis (PFGE) to the combination of ribosomal spacer PCR (RS-PCR) and virulence gene identification for typing of S. aureus strains. The hypothesis was that isolates that were previously characterized as contagious would be identified as genotype B and that the results of the two strain-typing methods would be comparable. Isolates were selected from a collection of S. aureus isolates from eight dairy farms. Mammary quarter milk somatic cell count (SCC) and N-acetyl-beta-d-gluconaminidase (NAGase) activity data were known and used to evaluate strain pathogenicity. RS PCR was performed with conventional gel electrophoresis, and PCR was used for toxin gene identification. RS-PCR patterns were associated with a specific virulence gene pattern, as previously reported. Five RS-PCR banding patterns were identified. None of the isolates were characterized as genotype B. No association between RS-PCR types and milk SCC was found; however, NAGase activity was significantly higher in milk from mammary glands infected with RS-PCR banding type 1 (RSP type 1) than in milk from those infected with RSP type 2. The discriminatory power values were 1.0 and 0.46 for PFGE and RS-PCR, respectively. These data suggest that genotype B may have a limited geographic distribution and that PFGE is more discriminatory than RS-PCR performed with conventional gel electrophoresis for typing of S. aureus isolates of bovine origin. PMID- 27194687 TI - A New Genomics-Driven Taxonomy of Bacteria and Archaea: Are We There Yet? AB - Taxonomy is often criticized for being too conservative and too slow and having limited relevance because it has not taken into consideration the latest methods and findings. Yet the cumulative work product of its practitioners underpins contemporary microbiology and serves as a principal means of shaping and referencing knowledge. Using methods drawn from the field of exploratory data analysis, this minireview examines the current state of the field as it transitions from a taxonomy based on 16S rRNA gene sequences to one based on whole-genome sequences and tests the validity of some commonly held beliefs. PMID- 27194686 TI - Improved Sensitivity of a Dual-Target HIV-1 Qualitative Test for Plasma and Dried Blood Spots. AB - The use of nucleic acid detection for HIV type 1 (HIV-1) detection is strongly recommended in infants <18 months of age, in whom serology is unreliable. This study evaluated the Cobas AmpliPrep/Cobas TaqMan HIV-1 Qualitative Test v2.0 (TaqMan HIV-1 Qual Test, v2.0), a dual-target total nucleic acid real-time PCR assay. The limit of detection (LOD) of the new test in plasma and dried blood spots (DBS) was determined with the 2nd International HIV-1 RNA WHO standard. The specificity of the assay was tested with EDTA plasma (n = 1,301) and DBS from HIV negative adults (n = 1,000). The sensitivity was determined using HIV-1-positive samples (n = 169 adult EDTA plasma, n = 172 adult DBS, and n = 100 infant DBS) that included group M, subtypes A to H, CRF01_AE, CRF02_AG, and groups O and N. All positive specimens and a subset of the negative specimens were also tested with the Abbott RealTime HIV-1 Qual assay (RealTime). The LOD of the TaqMan assay was 20 copies/ml in plasma and 300 copies/ml in DBS, with specificities of 99.8% in plasma and 99.9% in DBS. The TaqMan assay results were 100% concordant with RealTime results in EDTA plasma samples and in 100 HIV-1-negative adult DBS. Among 172 HIV-1-positive DBS from adults, the TaqMan assay showed positive results for all DBS while RealTime missed five DBS with low target concentrations. Infant DBS results were 100% concordant. The improved sensitivity of the Cobas AmpliPrep/Cobas TaqMan HIV-1 Qualitative Test, v2.0, compared to current commercially available assays may enable earlier diagnosis and treatment in adults and infants. The dual-target test may ensure HIV-1 detection even if a mutation is present in one of the two target regions. The DBS sample matrix facilitates virological testing in remote areas. PMID- 27194688 TI - Evaluation of Molecular Methods for Identification of Salmonella Serovars. AB - Classification by serotyping is the essential first step in the characterization of Salmonella isolates and is important for surveillance, source tracking, and outbreak detection. To improve detection and reduce the burden of salmonellosis, several rapid and high-throughput molecular Salmonella serotyping methods have been developed.The aim of this study was to compare three commercial kits, Salm SeroGen (Salm Sero-Genotyping AS-1 kit), Check&Trace (Check-Points), and xMAP (xMAP Salmonella serotyping assay), to the Salmonella genoserotyping array (SGSA) developed by our laboratory. They were assessed using a panel of 321 isolates that represent commonly reported serovars from human and nonhuman sources globally. The four methods correctly identified 73.8% to 94.7% of the isolates tested. The methods correctly identified 85% and 98% of the clinically important Salmonella serovars Enteritidis and Typhimurium, respectively. The methods correctly identified 75% to 100% of the nontyphoidal, broad host range Salmonella serovars, including Heidelberg, Hadar, Infantis, Kentucky, Montevideo, Newport, and Virchow. The sensitivity and specificity of Salmonella serovars Typhimurium and Enteritidis ranged from 85% to 100% and 99% to 100%, respectively.It is anticipated that whole-genome sequencing will replace serotyping in public health laboratories in the future. However, at present, it is approximately three times more expensive than molecular methods. Until consistent standards and methodologies are deployed for whole-genome sequencing, data analysis and interlaboratory comparability remain a challenge. The use of molecular serotyping will provide a valuable high-throughput alternative to traditional serotyping. This comprehensive analysis provides a detailed comparison of commercial kits available for the molecular serotyping of Salmonella. PMID- 27194689 TI - Follow-Up of External Quality Controls for PCR-Based Diagnosis of Whooping Cough in a Hospital Laboratory Network (Renacoq) and in Other Hospital and Private Laboratories in France. AB - The French National Reference Centre (NRC) for Whooping Cough carried out an external quality control (QC) analysis in 2010 for the PCR diagnosis of whooping cough. The main objective of the study was to assess the impact of this QC in the participating laboratories through a repeat analysis in 2012. PMID- 27194690 TI - Multicenter Evaluation of Meridian Bioscience HSV 1&2 Molecular Assay for Detection of Herpes Simplex Virus 1 and 2 from Clinical Cutaneous and Mucocutaneous Specimens. AB - Herpes simplex virus (HSV) causes acute and relapsing symptoms characterized by ulcerative lesions. Laboratory diagnosis of HSV in cutaneous or mucocutaneous lesions has historically been performed with the use of viral cell culture systems; however, these tests are laborious and suffer decreased sensitivity for advanced-stage lesions. The recent availability of FDA-cleared moderately complex assays has resulted in the increased use of molecular diagnostics for the routine detection of HSV in superficial swab specimens. We performed a clinical evaluation of the recently FDA-cleared illumigene HSV 1&2 loop-mediated isothermal amplification (LAMP) assay (Meridian Bioscience, Cincinnati OH) for the detection and differentiation of HSV-1 and HSV-2 in cutaneous and mucocutaneous swab specimens. A total of 1,153 clinical swab specimens were collected and tested at 7 different clinical centers. Each specimen was tested for the presence of HSV-1 and HSV-2 using the illumigene assay, and results were compared to those of the enzyme-linked virus-inducible system (ELVIS) as the reference method. Overall, the illumigene assay demonstrated a sensitivity and specificity of 94.8% and 95.5%, respectively, for the detection of HSV-1. Detection of HSV-2 was similar, with a sensitivity of 98.9% and a specificity of 95.5%. Discrepant analysis was performed using an alternative molecular test (AmpliVue HSV1+2 assay; Quidel Molecular, San Diego, CA) on 91/99 specimens that were recorded as false positive (FP) or false negative (FN) compared to the reference method. In total, 57/78 (73%) FP and 9/13 (69%) FN illumigene results were supported by the AmpliVue result. The illumigene HSV 1&2 assay demonstrated high sensitivity and specificity to detect and differentiate HSV in clinical specimens and identified 57 additional specimens that were positive for HSV compared to culture. The use of LAMP eliminates the need for the cycling of temperatures and provides results in less than 60 min, with approximately 2 min of hands-on time per specimen. PMID- 27194691 TI - Feasibility and Operational Performance of Tuberculosis Detection by Loop Mediated Isothermal Amplification Platform in Decentralized Settings: Results from a Multicenter Study. AB - Currently available nucleic acid amplification platforms for tuberculosis (TB) detection are not designed to be simple or inexpensive enough to implement in decentralized settings in countries with a high burden of disease. The loop mediated isothermal amplification platform (LAMP) may change this. We conducted a study in adults with symptoms suggestive of TB in India, Uganda, and Peru to establish the feasibility of using TB-LAMP (Eiken Chemical Co.) in microscopy laboratories compared with using smear microscopy against a reference standard of solid and liquid cultures. Operational characteristics were evaluated as well. A total of 1,777 participants met the eligibility criteria and were included for analysis. Overall, TB-LAMP sensitivities among culture-positive samples were 97.2% (243/250; 95% confidence interval [CI], 94.3% to 98.2%) and 62.0% (88/142; 95% CI, 53.5% to 70.0%) for smear-positive and smear-negative TB, respectively, but varied widely by country and operator. Specificities ranged from 94.5% (446/472; 95% CI, 92.0% to 96.4%) to 98.0% (350/357; 95% CI, 96.0% to 99.2%) by country. A root cause analysis identified high temperatures, high humidity, and/or low reaction volumes as possible causes for false-positive results, as they may result in nonspecific amplification. The study was repeated in India with training focused on vulnerable steps and an updated protocol; 580 participants were included for analysis. Specificity in the repeat trial was 96.6% (515/533; 95% CI, 94.7% to 97.9%). To achieve acceptable performance of LAMP at the microscopy center level, significant training and infrastructure requirements are necessary. PMID- 27194692 TI - Identification of Goose-Origin Parvovirus as a Cause of Newly Emerging Beak Atrophy and Dwarfism Syndrome in Ducklings. AB - A recent epizootic outbreak, in China, of duck beak atrophy and dwarfism syndrome (BADS) was investigated using electron microscopic, genetic, and virological studies, which identified a parvovirus with a greater similarity to goose parvovirus (GPV) (97% protein homology) than to Muscovy duck parvovirus (MDPV) (90% protein homology). The new virus, provisionally designated GPV-QH15, was found to be antigenically more closely related to GPV than to MDPV in a virus neutralization assay. These findings were further supported by phylogenetic analysis showing that GPV-QH15 evolved from goose lineage parvoviruses, rather than from Muscovy duck- or other duck species-related parvoviruses. In all, two genetic lineages (GPV I and GPV II) were identified from the GPV samples analyzed, and GPV-QH15 was found to be closely clustered with two known goose origin parvoviruses (GPVa2006 and GPV1995), together forming a distinctive GPV IIa sublineage. Finally, structural modeling revealed that GPV-QH15 and the closely related viruses GPVa2006 and GPV1995 possessed identical clusters of receptor-interacting amino acid residues in the VP2 protein, a major determinant of viral receptor binding and host specificity. Significantly, these three viruses differed from MDPVs and other GPVs at these positions. Taken together, these results suggest that GPV-QH15 represents a new variant of goose-origin parvovirus that currently circulates in ducklings and causes BADS, a syndrome reported previously in Europe. This new finding highlights the need for future surveillance of GPV-QH15 in poultry in order to gain a better understanding of both the evolution and the biology of this emerging parvovirus. PMID- 27194693 TI - Treponema pallidum Strain Types and Association with Macrolide Resistance in Sydney, Australia: New TP0548 Gene Types Identified. AB - Strain typing of Treponema pallidum, using the three-target enhanced classification scheme, was performed with 191 samples obtained between 2004 and 2011 in Sydney, Australia. The most common strain type was 14d/g (92/191 samples [48%]). Two new TP0548 gene types were detected (m and n). Strain type was associated with macrolide resistance and possible acquisition outside Australia. PMID- 27194694 TI - Collateral damage or a shadow of safety? The effects of signalling heterospecific neighbours on the risks of parasitism and predation. AB - Although males often display from mixed-species aggregations, the influence of nearby heterospecifics on risks associated with sexual signalling has not been previously examined. We tested whether predation and parasitism risks depend on proximity to heterospecific signallers. Using field playback experiments with calls of two species that often display from the same ponds, tungara frogs and hourglass treefrogs, we tested two hypotheses: (1) calling near heterospecific signallers attractive to eavesdroppers results in increased attention from predatory bats and parasitic midges (collateral damage hypothesis) or (2) calling near heterospecific signallers reduces an individual's predation and parasitism risks, as eavesdroppers are drawn to the heterospecifics (shadow of safety hypothesis). Bat visitation was not affected by calling neighbours. The number of frog-biting midges attracted to hourglass treefrog calls, however, rose threefold when played near tungara calls, supporting the collateral damage hypothesis. We thus show that proximity to heterospecific signallers can drastically alter both the absolute risks of signalling and the relative strengths of pressures from predation and parasitism. Through these mechanisms, interactions between heterospecific guild members are likely to influence the evolution of signalling strategies and the distribution of species at both local and larger scales. PMID- 27194695 TI - Cell proliferation and migration during early development of a symbiotic scleractinian coral. AB - In scleractinian reef-building corals, patterns of cell self-renewal, migration and death remain virtually unknown, limiting our understanding of cellular mechanisms underlying initiation of calcification, and ontogenesis of the endosymbiotic dinoflagellate relationship. In this study, we pulse-labelled the coral Stylophora pistillata for 24 h with BrdU at four life stages (planula, early metamorphosis, primary polyp and adult colony) to investigate coral and endosymbiont cell proliferation during development, while simultaneously recording TUNEL-positive (i.e. apoptotic) nuclei. In the primary polyp, the fate of BrdU-labelled cells was tracked during a 3-day chase. The pharynx and gastrodermis were identified as the most proliferative tissues in the developing polyp, and BrdU-labelled cells accumulated in the surface pseudostratified epithelium and the skeletogenic calicodermis during the chase, revealing cell migration to these epithelia. Surprisingly, the lowest cell turnover was recorded in the calicodermis at all stages, despite active, ongoing skeletal deposition. In dinoflagellate symbionts, DNA synthesis was systematically higher than coral host gastrodermis, especially in planula and early metamorphosis. The symbiont to host cell ratio remained constant, however, indicating successive post-mitotic control mechanisms by the host of its dinoflagellate density in early life stages, increasingly shifting to apoptosis in the growing primary polyp. PMID- 27194696 TI - Tiny vampires in ancient seas: evidence for predation via perforation in fossils from the 780-740 million-year-old Chuar Group, Grand Canyon, USA. AB - One explanation for the Early Neoproterozoic expansion of eukaryotes is the appearance of eukaryovorous predators-i.e. protists that preyed on other protists. Evidence for eukaryovory at this time, however, is indirect, based on inferences from character state reconstructions and molecular clocks, and on the presence of possible defensive structures in some protistan fossils. Here I describe 0.1-3.4 um circular holes in seven species of organic-walled microfossils from the 780-740 million-year-old Chuar Group, Grand Canyon, Arizona, USA, that are similar to those formed today by predatory protists that perforate the walls of their prey to consume the contents inside. Although best known in the vampyrellid amoebae, this 'vampire-like' behaviour is widespread among eukaryotes, making it difficult to infer confidently the identity of the predator. Nonetheless, the identity of the prey is clear: some-and perhaps all-of the fossils are eukaryotes. These holes thus provide the oldest direct evidence for predation on eukaryotes. Larger circular and half-moon-shaped holes in vase shaped microfossils from the upper part of the unit may also be the work of 'tiny vampires', suggesting a diversity of eukaryovorous predators lived in the ancient Chuar sea. PMID- 27194698 TI - Acclimatization to high-variance habitats does not enhance physiological tolerance of two key Caribbean corals to future temperature and pH. AB - Corals are acclimatized to populate dynamic habitats that neighbour coral reefs. Habitats such as seagrass beds exhibit broad diel changes in temperature and pH that routinely expose corals to conditions predicted for reefs over the next 50 100 years. However, whether such acclimatization effectively enhances physiological tolerance to, and hence provides refuge against, future climate scenarios remains unknown. Also, whether corals living in low-variance habitats can tolerate present-day high-variance conditions remains untested. We experimentally examined how pH and temperature predicted for the year 2100 affects the growth and physiology of two dominant Caribbean corals (Acropora palmata and Porites astreoides) native to habitats with intrinsically low (outer reef terrace, LV) and/or high (neighbouring seagrass, HV) environmental variance. Under present-day temperature and pH, growth and metabolic rates (calcification, respiration and photosynthesis) were unchanged for HV versus LV populations. Superimposing future climate scenarios onto the HV and LV conditions did not result in any enhanced tolerance to colonies native to HV. Calcification rates were always lower for elevated temperature and/or reduced pH. Together, these results suggest that seagrass habitats may not serve as refugia against climate change if the magnitude of future temperature and pH changes is equivalent to neighbouring reef habitats. PMID- 27194697 TI - Evolution of long-term coloration trends with biochemically unstable ingredients. AB - The evolutionarily persistent and widespread use of carotenoid pigments in animal coloration contrasts with their biochemical instability. Consequently, evolution of carotenoid-based displays should include mechanisms to accommodate or limit pigment degradation. In birds, this could involve two strategies: (i) evolution of a moult immediately prior to the mating season, enabling the use of particularly fast-degrading carotenoids and (ii) evolution of the ability to stabilize dietary carotenoids through metabolic modification or association with feather keratins. Here, we examine evolutionary lability and transitions between the two strategies across 126 species of birds. We report that species that express mostly unmodified, fast-degrading, carotenoids have pre-breeding moults, and a particularly short time between carotenoid deposition and the subsequent breeding season. Species that expressed mostly slow-degrading carotenoids in their plumage accomplished this through increased metabolic modification of dietary carotenoids, and the selective expression of these slow-degrading compounds. In these species, the timing of moult was not associated with carotenoid composition of plumage displays. Using repeated samples from individuals of one species, we found that metabolic modification of dietary carotenoids significantly slowed their degradation between moult and breeding season. Thus, the most complex and colourful ornamentation is likely the most biochemically stable in birds, and depends less on ecological factors, such as moult timing and migration tendency. We suggest that coevolution of metabolic modification, selective expression and biochemical stability of plumage carotenoids enables the use of unstable pigments in long-term evolutionary trends in plumage coloration. PMID- 27194699 TI - The emergence of latent infection in the early evolution of Mycobacterium tuberculosis. AB - Mycobacterium tuberculosis has an unusual natural history in that the vast majority of its human hosts enter a latent state that is both non-infectious and devoid of any symptoms of disease. From the pathogen perspective, it seems counterproductive to relinquish reproductive opportunities to achieve a detente with the host immune response. However, a small fraction of latent infections reactivate to the disease state. Thus, latency has been argued to provide a safe harbour for future infections which optimizes the persistence of M. tuberculosis in human populations. Yet, if a pathogen begins interactions with humans as an active disease without latency, how could it begin to evolve latency properties without incurring an immediate reproductive disadvantage? We address this question with a mathematical model. Results suggest that the emergence of tuberculosis latency may have been enabled by a mechanism akin to cryptic genetic variation in that detrimental latency properties were hidden from natural selection until their expression became evolutionarily favoured. PMID- 27194700 TI - Major evolutionary transitions of life, metabolic scaling and the number and size of mitochondria and chloroplasts. AB - We investigate the effects of trophic lifestyle and two types of major evolutionary transitions in individuality-the endosymbiotic acquisition of organelles and development of multicellularity-on organellar and cellular metabolism and allometry. We develop a quantitative framework linking the size and metabolic scaling of eukaryotic cells to the abundance, size and metabolic scaling of mitochondria and chloroplasts and analyse a newly compiled, unprecedented database representing unicellular and multicellular cells covering diverse phyla and tissues. Irrespective of cellularity, numbers and total volumes of mitochondria scale linearly with cell volume, whereas chloroplasts scale sublinearly and sizes of both organelles remain largely invariant with cell size. Our framework allows us to estimate the metabolic scaling exponents of organelles and cells. Photoautotrophic cells and organelles exhibit photosynthetic scaling exponents always less than one, whereas chemoheterotrophic cells and organelles have steeper respiratory scaling exponents close to one. Multicellularity has no discernible effect on the metabolic scaling of organelles and cells. In contrast, trophic lifestyle has a profound and uniform effect, and our results suggest that endosymbiosis fundamentally altered the metabolic scaling of free-living bacterial ancestors of mitochondria and chloroplasts, from steep ancestral scaling to a shallower scaling in their endosymbiotic descendants. PMID- 27194701 TI - The peripheral olfactory code in Drosophila larvae contains temporal information and is robust over multiple timescales. AB - We studied the electrophysiological activity of two classes of Drosophila melanogaster larval olfactory sensory neurons (OSNs), Or24a and Or74a, in response to 1 s stimulation with butanol, octanol, 2-heptanone, and propyl acetate. Each odour/OSN combination produced unique responses in terms of spike count and temporal profile. We used a classifier algorithm to explore the information content of OSN activity, and showed that as well as spike count, the activity of these OSNs included temporal information that enabled the classifier to accurately identify odours. The responses of OSNs during continuous odour exposure (5 and 20 min) showed that both types of neuron continued to respond, with no complete adaptation, and with no change to their ability to encode temporal information. Finally, we exposed larvae to octanol for 3 days and found only minor quantitative changes in OSN response to odours, indicating that the larval peripheral code is robust when faced with long-term exposure to odours, such as would be found in a natural context. PMID- 27194702 TI - Eighty-five million years of Pacific Ocean gyre ecosystem structure: long-term stability marked by punctuated change. AB - While the history of taxonomic diversification in open ocean lineages of ray finned fish and elasmobranchs is increasingly known, the evolution of their roles within the open ocean ecosystem remains poorly understood. To assess the relative importance of these groups through time, we measured the accumulation rate of microfossil fish teeth and elasmobranch dermal denticles (ichthyoliths) in deep sea sediment cores from the North and South Pacific gyres over the past 85 million years (Myr). We find three distinct and stable open ocean ecosystem structures, each defined by the relative and absolute abundance of elasmobranch and ray-finned fish remains. The Cretaceous Ocean (pre-66 Ma) was characterized by abundant elasmobranch denticles, but low abundances of fish teeth. The Palaeogene Ocean (66-20 Ma), initiated by the Cretaceous/Palaeogene mass extinction, had nearly four times the abundance of fish teeth compared with elasmobranch denticles. This Palaeogene Ocean structure remained stable during the Eocene greenhouse (50 Ma) and the Eocene-Oligocene glaciation (34 Ma), despite large changes in the overall accumulation of both groups during those intervals, suggesting that climate change is not a primary driver of ecosystem structure. Dermal denticles virtually disappeared from open ocean ichthyolith assemblages approximately 20 Ma, while fish tooth accumulation increased dramatically in variability, marking the beginning of the Modern Ocean. Together, these results suggest that open ocean fish community structure is stable on long timescales, independent of total production and climate change. The timing of the abrupt transitions between these states suggests that the transitions may be due to interactions with other, non-preserved pelagic consumer groups. PMID- 27194703 TI - Reciprocal relationships between behaviour and parasites suggest that negative feedback may drive flexibility in male reproductive behaviour. AB - Parasites are ubiquitous components of the environment that contribute to behavioural and life-history variation among hosts. Although it is well known that host behaviour can affect parasite infection risk and that parasites can alter host behaviour, the potential for dynamic feedback between these processes is poorly characterized. Using Grant's gazelle (Nanger granti) as a model, we tested for reciprocal effects of behaviour on parasites and parasites on behaviour to understand whether behaviour-parasite feedback could play a role in maintaining variation in male reproductive behaviour. Adult male gazelles either defend territories to attract mates or reside in bachelor groups. Territoriality is highly variable both within- and between-individuals, suggesting that territory maintenance is costly. Using a combination of longitudinal and experimental studies, we found that individual males transition frequently between territorial and bachelor reproductive status, and that elevated parasite burdens are a cost of territoriality. Moreover, among territorial males, parasites suppress aspects of behaviour related to territory maintenance and defence. These results suggest that territorial behaviour promotes the accumulation of parasites in males, and these parasites dampen the very behaviours required for territory maintenance. Our findings suggest that reciprocal feedback between host behaviour and parasitism could be a mechanism maintaining variation in male reproductive behaviour in the system. PMID- 27194704 TI - Individual fluctuations in toxin levels affect breeding site fidelity in a chemically defended amphibian. AB - Behaviours that influence habitat selection strongly determine species movement patterns. One component of animal behaviour that largely influences movement patterns and habitat choice is site fidelity. California newts (family Salamandridae) demonstrate remarkable site fidelity, typically homing to the same pool of a stream each breeding season. Individuals often occupy a specific pool throughout the breeding season, but some males shift among breeding pools, altering their set of potential mates, competitors, and predators. In this study, we measured dermal concentrations of the chemical defence compound tetrodotoxin (TTX) in recaptured male California newts (Taricha torosa) over five breeding seasons to evaluate whether relative TTX concentrations are associated with breeding site fidelity in the field. Our five years of field sampling indicates that TTX concentrations of individuals and group means fluctuate tremendously, implying that TTX is not a stable phenotypic trait. Despite such fluctuations, we found that an individual's relative TTX concentration explains fidelity to a breeding pool and suggests that newts may be able to assess both their own concentrations of TTX and that of conspecifics to make decisions about remaining in or abandoning a breeding pool. These results provide us a novel dimension to chemical defence phenotypes in nature and their ecological consequences, potentially requiring a re-evaluation of the coevolutionary dynamics of predation pressure on toxin-laden organisms. PMID- 27194705 TI - Host-parasitoid evolution in a metacommunity. AB - Patch size and isolation are predicted to alter both species diversity and evolution; yet, there are few empirical examples of eco-evolutionary feedback in metacommunities. We tested three hypotheses about eco-evolutionary feedback in a gall-forming fly, Eurosta solidaginis and two of its natural enemies that select for opposite traits: (i) specialization and poor dispersal ability constrain a subset of natural enemies from occupying small and isolated patches, (ii) this constraint alters selection on the gall fly, causing phenotypic shifts towards traits resistant to generalist and dispersive enemies in small and isolated patches, and (iii) reduced dispersal evolves in small, isolated populations. We sampled patches in a natural metacommunity and found support for all hypotheses; Eurosta's specialist wasp parasitoid attacked fewer galls in small and isolated patches, generating a selection gradient that favoured small galls resistant to predation by a dispersive and generalist bird predator. Phenotype distributions matched this selection gradient, and these phenotypic differences were maintained in a common garden experiment. Finally, we found lower dispersal abilities in small and isolated patches, a phenotypic shift that aids in the maintenance of local adaptation. We suggest that the trophic rank and the species traits of consumers are central to evolution in metacommunities. PMID- 27194707 TI - MS5 Mediates Early Meiotic Progression and Its Natural Variants May Have Applications for Hybrid Production in Brassica napus. AB - During meiotic prophase I, chromatin undergoes dynamic changes to establish a structural basis for essential meiotic events. However, the mechanism that coordinates chromosome structure and meiotic progression remains poorly understood in plants. Here, we characterized a spontaneous sterile mutant MS5(b)MS5(b) in oilseed rape (Brassica napus) and found its meiotic chromosomes were arrested at leptotene. MS5 is preferentially expressed in reproductive organs and encodes a Brassica-specific protein carrying conserved coiled-coil and DUF626 domains with unknown function. MS5 is essential for pairing of homologs in meiosis, but not necessary for the initiation of DNA double-strand breaks. The distribution of the axis element-associated protein ASY1 occurs independently of MS5, but localization of the meiotic cohesion subunit SYN1 requires functional MS5. Furthermore, both the central element of the synaptonemal complex and the recombination element do not properly form in MS5(b)MS5(b) mutants. Our results demonstrate that MS5 participates in progression of meiosis during early prophase I and its allelic variants lead to differences in fertility, which may provide a promising strategy for pollination control for heterosis breeding. PMID- 27194706 TI - Genetic Analysis of Physcomitrella patens Identifies ABSCISIC ACID NON RESPONSIVE, a Regulator of ABA Responses Unique to Basal Land Plants and Required for Desiccation Tolerance. AB - The anatomically simple plants that first colonized land must have acquired molecular and biochemical adaptations to drought stress. Abscisic acid (ABA) coordinates responses leading to desiccation tolerance in all land plants. We identified ABA nonresponsive mutants in the model bryophyte Physcomitrella patens and genotyped a segregating population to map and identify the ABA NON-RESPONSIVE (ANR) gene encoding a modular protein kinase comprising an N-terminal PAS domain, a central EDR domain, and a C-terminal MAPKKK-like domain. anr mutants fail to accumulate dehydration tolerance-associated gene products in response to drought, ABA, or osmotic stress and do not acquire ABA-dependent desiccation tolerance. The crystal structure of the PAS domain, determined to 1.7-A resolution, shows a conserved PAS-fold that dimerizes through a weak dimerization interface. Targeted mutagenesis of a conserved tryptophan residue within the PAS domain generates plants with ABA nonresponsive growth and strongly attenuated ABA-responsive gene expression, whereas deleting this domain retains a fully ABA-responsive phenotype. ANR orthologs are found in early-diverging land plant lineages and aquatic algae but are absent from more recently diverged vascular plants. We propose that ANR genes represent an ancestral adaptation that enabled drought stress survival of the first terrestrial colonizers but were lost during land plant evolution. PMID- 27194709 TI - Vascular Cell Induction Culture System Using Arabidopsis Leaves (VISUAL) Reveals the Sequential Differentiation of Sieve Element-Like Cells. AB - Cell differentiation is a complex process involving multiple steps, from initial cell fate specification to final differentiation. Procambial/cambial cells, which act as vascular stem cells, differentiate into both xylem and phloem cells during vascular development. Recent studies have identified regulatory cascades for xylem differentiation. However, the molecular mechanism underlying phloem differentiation is largely unexplored due to technical challenges. Here, we established an ectopic induction system for phloem differentiation named Vascular Cell Induction Culture System Using Arabidopsis Leaves (VISUAL). Our results verified similarities between VISUAL-induced Arabidopsis thaliana phloem cells and in vivo sieve elements. We performed network analysis using transcriptome data with VISUAL to dissect the processes underlying phloem differentiation, eventually identifying a factor involved in the regulation of the master transcription factor gene APL Thus, our culture system opens up new avenues not only for genetic studies of phloem differentiation, but also for future investigations of multidirectional differentiation from vascular stem cells. PMID- 27194711 TI - Shifting Paradigms and the Term Schizophrenia. PMID- 27194708 TI - The Proteasome Stress Regulon Is Controlled by a Pair of NAC Transcription Factors in Arabidopsis. AB - Proteotoxic stress, which is generated by the accumulation of unfolded or aberrant proteins due to environmental or cellular perturbations, can be mitigated by several mechanisms, including activation of the unfolded protein response and coordinated increases in protein chaperones and activities that direct proteolysis, such as the 26S proteasome. Using RNA-seq analyses combined with chemical inhibitors or mutants that induce proteotoxic stress by impairing 26S proteasome capacity, we defined the transcriptional network that responds to this stress in Arabidopsis thaliana This network includes genes encoding core and assembly factors needed to build the complete 26S particle, alternative proteasome capping factors, enzymes involved in protein ubiquitylation/deubiquitylation and cellular detoxification, protein chaperones, autophagy components, and various transcriptional regulators. Many loci in this proteasome-stress regulon contain a consensus cis-element upstream of the transcription start site, which was previously identified as a binding site for the NAM/ATAF1/CUC2 78 (NAC78) transcription factor. Double mutants disrupting NAC78 and its closest relative NAC53 are compromised in the activation of this regulon and notably are strongly hypersensitive to the proteasome inhibitors MG132 and bortezomib. Given that NAC53 and NAC78 homo- and heterodimerize, we propose that they work as a pair in activating the expression of numerous factors that help plants survive proteotoxic stress and thus play a central regulatory role in maintaining protein homeostasis. PMID- 27194712 TI - High serum creatinine nonlinearity: a renal vital sign? AB - Patients with chronic kidney disease (CKD) may have nonlinear serum creatinine concentration (SC) trajectories, especially as CKD progresses. Variability in SC is associated with renal failure and death. However, present methods for measuring SC variability are unsatisfactory because they blend information about SC slope and variance. We propose an improved method for defining and calculating a patient's SC slope and variance so that they are mathematically distinct, and we test these methods in a large sample of US veterans, examining the correlation of SC slope and SC nonlinearity (SCNL) and the association of SCNL with time to stage 4 CKD (CKD4) and death. We found a strong correlation between SCNL and rate of CKD progression, time to CKD4, and time to death, even in patients with normal renal function. We therefore argue that SCNL may be a measure of renal autoregulatory dysfunction that provides an early warning sign for CKD progression. PMID- 27194710 TI - Education, material condition and physical functioning trajectories in middle aged and older adults in Central and Eastern Europe: a cross-country comparison. AB - BACKGROUND: Two competing hypotheses, cumulative advantage/disadvantage and age as-leveller, have been proposed to explain the contradictory findings on socioeconomic differences in health over the lifespan. To test these hypotheses, this investigation examined the influence of educational attainment and material condition on individual trajectories of physical functioning (PF) in unexplored ageing populations in Central and Eastern Europe. METHODS: 28 783 men and women aged 45-69 years selected from populations in seven Czech towns, Krakow (Poland) and Novosibirsk (Russia). PF was measured by the Physical Functioning Subscale (PF-10) of the Short-Form-36 questionnaire (SF-36) at baseline and three subsequent occasions. The highest educational attainment was self-reported at baseline, and material condition was captured by the sum score of 12 household amenities and assets. RESULTS: In all cohorts, participants with a university degree had the highest PF-10 score at baseline and slowest rate of decline in the score during follow-up, while the lowest baseline scores and fastest decline rate were found in participants with less than secondary education in all cohorts and in Russians with secondary education. Similar disparities in the baseline PF-10 score and decline rate were observed across tertiles of material condition, but differences in decline rates across the three tertiles among Czechs or between the lower two tertiles among Russians were not statistically significant. CONCLUSIONS: Disparities in PF by educational attainment and material condition among middle-aged and older adults in Central and Eastern Europe existed at baseline and widened during ~10 years of follow-up, supporting the cumulative advantage/disadvantage hypothesis. PMID- 27194713 TI - Pyridoxamine reduces postinjury fibrosis and improves functional recovery after acute kidney injury. AB - Acute kidney injury (AKI) is a common and independent risk factor for death and chronic kidney disease (CKD). Despite promising preclinical data, there is no evidence that antioxidants reduce the severity of injury, increase recovery, or prevent CKD in patients with AKI. Pyridoxamine (PM) is a structural analog of vitamin B6 that interferes with oxidative macromolecular damage via a number of different mechanisms and is in a phase 3 clinical efficacy trial to delay CKD progression in patients with diabetic kidney disease. Because oxidative stress is implicated as one of the main drivers of renal injury after AKI, the ability of PM to interfere with multiple aspects of oxidative damage may be favorable for AKI treatment. In these studies we therefore evaluated PM treatment in a mouse model of AKI. Pretreatment with PM caused a dose-dependent reduction in acute tubular injury, long-term postinjury fibrosis, as well as improved functional recovery after ischemia-reperfusion AKI (IR-AKI). This was associated with a dose dependent reduction in the oxidative stress marker isofuran-to-F2-isoprostane ratio, indicating that PM reduces renal oxidative damage post-AKI. PM also reduced postinjury fibrosis when administered 24 h after the initiating injury, but this was not associated with improvement in functional recovery after IR-AKI. This is the first report showing that treatment with PM reduces short- and long term injury, fibrosis, and renal functional recovery after IR-AKI. These preclinical findings suggest that PM, which has a favorable clinical safety profile, holds therapeutic promise for AKI and, most importantly, for prevention of adverse long-term outcomes after AKI. PMID- 27194716 TI - Postischemic microvasculopathy and endothelial progenitor cell-based therapy in ischemic AKI: update and perspectives. AB - Acute kidney injury (AKI) dramatically increases mortality of hospitalized patients. Incidences have been increased in recent years. The most frequent cause is transient renal hypoperfusion or ischemia which induces significant tubular cell dysfunction/damage. In addition, two further events take place: interstitial inflammation and microvasculopathy (MV). The latter evolves within minutes to hours postischemia and may result in permanent deterioration of the peritubular capillary network, ultimately increasing the risk for chronic kidney disease (CKD) in the long term. In recent years, our understanding of the molecular/cellular processes responsible for acute and sustained microvasculopathy has increasingly been expanded. The methodical approaches for visualizing impaired peritubular blood flow and increased vascular permeability have been optimized, even allowing the depiction of tissue abnormalities in a three-dimensional manner. In addition, endothelial dysfunction, a hallmark of MV, has increasingly been recognized as an inductor of both vascular malfunction and interstitial inflammation. In this regard, so-called regulated necrosis of the endothelium could potentially play a role in postischemic inflammation. Endothelial progenitor cells (EPCs), represented by at least two major subpopulations, have been shown to promote vascular repair in experimental AKI, not only in the short but also in the long term. The discussion about the true biology of the cells continues. It has been proposed that early EPCs are most likely myelomonocytic in nature, and thus they may simply be termed proangiogenic cells (PACs). Nevertheless, they reliably protect certain types of tissues/organs from ischemia-induced damage, mostly by modulating the perivascular microenvironment in an indirect manner. The aim of the present review is to summarize the current knowledge on postischemic MV and EPC-mediated renal repair. PMID- 27194715 TI - Heat shock factor 1 induces crystallin-alphaB to protect against cisplatin nephrotoxicity. AB - Cisplatin, a wildly used chemotherapy drug, induces nephrotoxicity that is characterized by renal tubular cell apoptosis. In response to toxicity, tubular cells can activate cytoprotective mechanisms, such as the heat shock response. However, the role and regulation of the heat shock response in cisplatin-induced nephrotoxicity remain largely unclear. In the present study, we demonstrated the induction of heat shock factor (Hsf)1 and the small heat shock protein crystallin alphaB (CryAB) during cisplatin nephrotoxicity in mice. Consistently, cisplatin induced Hsf1 and CryAB in a cultured renal proximal tubular cells (RPTCs). RPTCs underwent apoptosis during cisplatin treatment, which was increased when Hsf1 was knocked down. Transfection or restoration of Hsf1 into Hsf1 knockdown cells suppressed cisplatin-induced apoptosis, further supporting a cytoprotective role of Hsf1 and its associated heat shock response. Moreover, Hsf1 knockdown increased Bax translocation to mitochondria and cytochrome c release into the cytosol. In RPTCs, Hsf1 knockdown led to a specific downregulation of CryAB. Transfection of CryAB into Hsf1 knockdown cells diminished their sensitivity to cisplatin-induced apoptosis, suggesting that CryAB may be a key mediator of the cytoprotective effect of Hsf1. Taken together, these results demonstrate a heat shock response in cisplatin nephrotoxicity that is mediated by Hsf1 and CryAB to protect tubular cells against apoptosis. PMID- 27194717 TI - Perioperative glutamine supplementation restores disturbed renal arginine synthesis after open aortic surgery: a randomized controlled clinical trial. AB - Postoperative renal failure is a common complication after open repair of an abdominal aortic aneurysm. The amino acid arginine is formed in the kidneys from its precursor citrulline, and citrulline is formed from glutamine in the intestines. Arginine enhances the function of the immune and cardiovascular systems, which is important for recovery after surgery. We hypothesized that renal arginine production is diminished after ischemia-reperfusion injury caused by clamping of the aorta during open abdominal aortic surgery and that parenteral glutamine supplementation might compensate for this impaired arginine synthesis. This open-label clinical trial randomized patients who underwent clamping of the aorta during open abdominal aortic surgery to receive a perioperative supplement of intravenous alanyl-glutamine (0.5 g.kg(-1).day(-1); group A, n = 5) or no supplement (group B, n = 5). One day after surgery, stable isotopes and tracer methods were used to analyze the metabolism and conversion of glutamine, citrulline, and arginine. Whole body plasma flux of glutamine, citrulline, and arginine was significantly higher in group A than in group B (glutamine: 391 +/- 34 vs. 258 +/- 19 MUmol.kg(-1).h(-1), citrulline: 5.7 +/- 0.4 vs. 2.8 +/- 0.4 MUmol.kg(-1).h(-1), and arginine: 50 +/- 4 vs. 26 +/- 2 MUmol.kg(-1).h(-1), P < 0.01), as was the synthesis of citrulline from glutamine (4.8 +/- 0.7 vs. 1.6 +/- 0.3 MUmol.kg(-1).h(-1)), citrulline from arginine (2.3 +/- 0.3 vs. 0.96 +/- 0.1 MUmol.kg(-1).h(-1)), and arginine from glutamine (7.7 +/- 0.4 vs. 2.8 +/- 0.2 MUmol.kg(-1).h(-1)), respectively (P < 0.001 for all). In conclusion, the production of citrulline and arginine is severely reduced after clamping during aortic surgery. This study shows that an intravenous supplement of glutamine increases the production of citrulline and arginine and compensates for the inhibitory effect of ischemia-reperfusion injury. PMID- 27194714 TI - The proximal tubule is the primary target of injury and progression of kidney disease: role of the glomerulotubular junction. AB - There is an alarming global increase in the incidence of end-stage kidney disease, for which early biomarkers and effective treatment options are lacking. Largely based on the histology of the end-stage kidney and on the model of unilateral ureteral obstruction, current investigation is focused on the pathogenesis of renal interstitial fibrosis as a central mechanism in the progression of chronic kidney disease (CKD). It is now recognized that cumulative episodes of acute kidney injury (AKI) can lead to CKD, and, conversely, CKD is a risk factor for AKI. Based on recent and historic studies, this review shifts attention from the glomerulus and interstitium to the proximal tubule as the primary sensor and effector in the progression of CKD as well as AKI. Packed with mitochondria and dependent on oxidative phosphorylation, the proximal tubule is particularly vulnerable to injury (obstructive, ischemic, hypoxic, oxidative, metabolic), resulting in cell death and ultimately in the formation of atubular glomeruli. Animal models of human glomerular and tubular disorders have provided evidence for a broad repertoire of morphological and functional responses of the proximal tubule, revealing processes of degeneration and repair that may lead to new therapeutic strategies. Most promising are studies that encompass the entire life cycle from fetus to senescence, recognizing epigenetic factors. The application of techniques in molecular characterization of tubule segments and the development of human kidney organoids may provide new insights into the mammalian kidney subjected to stress or injury, leading to biomarkers of early CKD and new therapies. PMID- 27194718 TI - Increased angiotensinogen expression, urinary angiotensinogen excretion, and tissue injury in nonclipped kidneys of two-kidney, one-clip hypertensive rats. AB - In angiotensin II (ANG II)-dependent hypertension, there is an angiotensin type 1 receptor-dependent amplification mechanism enhancing intrarenal angiotensinogen (AGT) formation and secretion in the tubular fluid. To evaluate the role of increased arterial pressure, AGT mRNA, protein expression, and urinary AGT (uAGT) excretion and tissue injury were assessed in both kidneys of two-kidney, one-clip Sprague-Dawley hypertensive rats subjected to left renal arterial clipping (0.25 mm gap). By 18-21 days, systolic arterial pressure increased to 180 +/- 3 mmHg, and uAGT increased. Water intake, body weights, 24-h urine volumes, and sodium excretion were similar. In separate measurements of renal function in anesthetized rats, renal plasma flow and glomerular filtration rate were similar in clipped and nonclipped kidneys and not different from those in sham rats, indicating that the perfusion pressure to the clipped kidneys remained within the autoregulatory range. The nonclipped kidneys exhibited increased urine flow and sodium excretion. The uAGT excretion was significantly greater in nonclipped kidneys compared with clipped and sham kidneys. AGT mRNA was 2.15-fold greater in the nonclipped kidneys compared with sham (1.0 +/- 0.1) or clipped (0.98 +/- 0.15) kidneys. AGT protein levels were also greater in the nonclipped kidneys. The nonclipped kidneys exhibited greater glomerular expansion and immune cell infiltration, medullary fibrosis, and cellular proliferation than the clipped kidneys. Because both kidneys have elevated ANG II levels, the greater tissue injury in the nonclipped kidneys indicates that an increased arterial pressure synergizes with increased intrarenal ANG II to stimulate AGT production and exert greater renal injury. PMID- 27194719 TI - 20-HETE and CYP4A2 omega-hydroxylase contribute to the elevated blood pressure in hyperandrogenemic female rats. AB - In male rats, androgen supplements increase 20-hydroxyeicosatetraenoic acid (20 HETE) via cytochrome P-450 (CYP)4A omega-hydroxylase and cause an increase in blood pressure (BP). In the present study, we determined the roles of 20-HETE and CYP4A2 on the elevated BP in hyperandrogenemic female rats. Chronic dihydrotestosterone (DHT) increased mean arterial pressure (MAP) in female Sprague-Dawley rats (96 +/- 2 vs. 108 +/- 2 mmHg, P < 0.05) and was associated with increased renal microvascular CYP4A2 mRNA expression (15-fold), endogenous renal 20-HETE (5-fold), and omega-hydroxylase activity (3-fold). Chronic DHT also increased MAP in low salt-fed Dahl salt-resistant female rats (81 +/- 4 vs. 95 +/ 1 mmHg, P < 0.05) but had no effect on MAP in Dahl salt-sensitive female rats (154 +/- 3 vs. 153 +/- 3 mmHg), which are known to be 20-HETE deficient. To test the role of CYP4A2, female CYP4A2(-/-) and SS.5(Bn) (wild type) rats were treated with DHT. DHT increased MAP in SS.5(Bn) female rats (104 +/- 1 vs. 128 +/- 1 mmHg, P < 0.05) but had no effect in CYP4A2(-/-) female rats (118 +/- 1 vs. 120 +/- 1 mmHg). Renal microvascular 20-HETE was reduced in control CYP4A2(-/-) female rats and was increased with DHT in SS.5(Bn) female rats (6-fold) but not CYP4A2(-/-) female rats. omega-Hydroxylase activity was 40% lower in control CYP4A2(-/-) female rats than in SS.5(Bn) female rats, and DHT decreased omega hydroxylase activity in SS.5(Bn) female rats (by 50%) but significantly increased omega-hydroxylase activity in CYP4A2(-/-) female rats (3-fold). These data suggest that 20-HETE via CYP4A2 contributes to the elevation in BP in hyperandrogenemic female rats. The data also suggest that 20-HETE synthesis inhibition may be effective in treating the elevated BP in women with hyperandrogenemia, such as women with polycystic ovary syndrome. PMID- 27194722 TI - Glucagon actions on the kidney revisited: possible role in potassium homeostasis. AB - It is now recognized that the metabolic disorders observed in diabetes are not, or not only due to the lack of insulin or insulin resistance, but also to elevated glucagon secretion. Accordingly, selective glucagon receptor antagonists are now proposed as a novel strategy for the treatment of diabetes. However, besides its metabolic actions, glucagon also influences kidney function. The glucagon receptor is expressed in the thick ascending limb, distal tubule, and collecting duct, and glucagon regulates the transepithelial transport of several solutes in these nephron segments. Moreover, it also influences solute transport in the proximal tubule, possibly by an indirect mechanism. This review summarizes the knowledge accumulated over the last 30 years about the influence of glucagon on the renal handling of electrolytes and urea. It also describes a possible novel role of glucagon in the short-term regulation of potassium homeostasis. Several original findings suggest that pancreatic alpha-cells may express a "potassium sensor" sensitive to changes in plasma K concentration and could respond by adapting glucagon secretion that, in turn, would regulate urinary K excretion. By their combined actions, glucagon and insulin, working in a combinatory mode, could ensure an independent regulation of both plasma glucose and plasma K concentrations. The results and hypotheses reviewed here suggest that the use of glucagon receptor antagonists for the treatment of diabetes should take into account their potential consequences on electrolyte handling by the kidney. PMID- 27194720 TI - Hippo signaling in the kidney: the good and the bad. AB - The Hippo signaling pathway is an evolutionarily conserved kinase cascade, playing multiple roles in embryonic development that controls organ size, cell proliferation, and apoptosis. At the center of this network lie the Hippo kinase target and downstream pathway effector Yes-associated protein (YAP) and its paralog TAZ. In its phosphorylated form, cytoplasmic YAP is sequestered in an inactive state. When it is dephosphorylated, YAP, a potent oncogene, is activated and relocates to the nucleus to interact with a number of transcription factors and signaling regulators that promote cell growth, differentiation, and survival. The identification of YAP activation in human cancers has made it an attractive target for chemotherapeutic drug development. Little is known to date about the function of the Hippo pathway in the kidney, but that is rapidly changing. Recent studies have shed light on the role of Hippo-YAP signaling in glomerular and lower urinary tract embryonic development, maintenance of podocyte homeostasis, the integrity of the glomerular filtration barrier, regulation of renal tubular cyst growth, renal epithelial injury in diabetes, and renal fibrogenesis. This review summarizes the current knowledge of the Hippo-YAP signaling axis in the kidney under normal and disease conditions. PMID- 27194723 TI - Oscillatory dynamics in a bacterial cross-protection mutualism. AB - Cooperation between microbes can enable microbial communities to survive in harsh environments. Enzymatic deactivation of antibiotics, a common mechanism of antibiotic resistance in bacteria, is a cooperative behavior that can allow resistant cells to protect sensitive cells from antibiotics. Understanding how bacterial populations survive antibiotic exposure is important both clinically and ecologically, yet the implications of cooperative antibiotic deactivation on the population and evolutionary dynamics remain poorly understood, particularly in the presence of more than one antibiotic. Here, we show that two Escherichia coli strains can form an effective cross-protection mutualism, protecting each other in the presence of two antibiotics (ampicillin and chloramphenicol) so that the coculture can survive in antibiotic concentrations that inhibit growth of either strain alone. Moreover, we find that daily dilutions of the coculture lead to large oscillations in the relative abundance of the two strains, with the ratio of abundances varying by nearly four orders of magnitude over the course of the 3-day period of the oscillation. At modest antibiotic concentrations, the mutualistic behavior enables long-term survival of the oscillating populations; however, at higher antibiotic concentrations, the oscillations destabilize the population, eventually leading to collapse. The two strains form a successful cross-protection mutualism without a period of coevolution, suggesting that similar mutualisms may arise during antibiotic treatment and in natural environments such as the soil. PMID- 27194721 TI - Klotho/fibroblast growth factor 23- and PTH-independent estrogen receptor-alpha mediated direct downregulation of NaPi-IIa by estrogen in the mouse kidney. AB - Estrogen treatment causes renal phosphate (Pi) wasting and hypophosphatemia in rats and humans; however, the signaling mechanisms mediating this effect are still poorly understood. To determine the specific roles of estrogen receptor isoforms (ERalpha and ERbeta) and the Klotho pathway in mediating these effects, we studied the effects of estrogen on renal Pi handling in female mice with null mutations of ERalpha or ERbeta or Klotho and their wild type (WT) using balance studies in metabolic cages. Estrogen treatment of WT and ERbeta knockout (KO) mice caused a significant reduction in food intake along with increased renal phosphate wasting. The latter resulted from a significant downregulation of NaPi IIa and NaPi-IIc protein abundance. The mRNA expression levels of both transporters were unchanged in estrogen-treated mice. These effects on both food intake and renal Pi handling were absent in ERalpha KO mice. Estrogen treatment of Klotho KO mice or parathyroid hormone (PTH)-depleted thyroparathyroidectomized mice exhibited a significant downregulation of NaPi-IIa with no change in the abundance of NaPi-IIc. Estrogen treatment of a cell line (U20S) stably coexpressing both ERalpha and ERbeta caused a significant downregulation of NaPi IIa protein when transiently transfected with a plasmid containing full-length or open-reading frame (ORF) 3'-untranslated region (UTR) but not 5'-UTR ORF of mouse NaPi-IIa transcript. In conclusion, estrogen causes phosphaturia and hypophosphatemia in mice. These effects result from downregulation of NaPi-IIa and NaPi-IIc proteins in the proximal tubule through the activation of ERalpha. The downregulation of NaPi-IIa by estrogen involves 3'-UTR of its mRNA and is independent of Klotho/fibroblast growth factor 23 and PTH signaling pathways. PMID- 27194724 TI - Broadly neutralizing epitopes in the Plasmodium vivax vaccine candidate Duffy Binding Protein. AB - Plasmodium vivax Duffy Binding Protein (PvDBP) is the most promising vaccine candidate for P. vivax malaria. The polymorphic nature of PvDBP induces strain specific immune responses, however, and the epitopes of broadly neutralizing antibodies are unknown. These features hamper the rational design of potent DBP based vaccines and necessitate the identification of globally conserved epitopes. Using X-ray crystallography, small-angle X-ray scattering, hydrogen-deuterium exchange mass spectrometry, and mutational mapping, we have defined epitopes for three inhibitory mAbs (mAbs 2D10, 2H2, and 2C6) and one noninhibitory mAb (3D10) that engage DBP. These studies expand the currently known inhibitory epitope repertoire by establishing protective motifs in subdomain three outside the receptor-binding and dimerization residues of DBP, and introduce globally conserved protective targets. All of the epitopes are highly conserved among DBP alleles. The identification of broadly conserved epitopes of inhibitory antibodies provides critical motifs that should be retained in the next generation of potent vaccines for P. vivax malaria. PMID- 27194726 TI - Reproducibility will only come with data liberation. PMID- 27194725 TI - LATERAL BRANCHING OXIDOREDUCTASE acts in the final stages of strigolactone biosynthesis in Arabidopsis. AB - Strigolactones are a group of plant compounds of diverse but related chemical structures. They have similar bioactivity across a broad range of plant species, act to optimize plant growth and development, and promote soil microbe interactions. Carlactone, a common precursor to strigolactones, is produced by conserved enzymes found in a number of diverse species. Versions of the MORE AXILLARY GROWTH1 (MAX1) cytochrome P450 from rice and Arabidopsis thaliana make specific subsets of strigolactones from carlactone. However, the diversity of natural strigolactones suggests that additional enzymes are involved and remain to be discovered. Here, we use an innovative method that has revealed a missing enzyme involved in strigolactone metabolism. By using a transcriptomics approach involving a range of treatments that modify strigolactone biosynthesis gene expression coupled with reverse genetics, we identified LATERAL BRANCHING OXIDOREDUCTASE (LBO), a gene encoding an oxidoreductase-like enzyme of the 2 oxoglutarate and Fe(II)-dependent dioxygenase superfamily. Arabidopsis lbo mutants exhibited increased shoot branching, but the lbo mutation did not enhance the max mutant phenotype. Grafting indicated that LBO is required for a graft transmissible signal that, in turn, requires a product of MAX1. Mutant lbo backgrounds showed reduced responses to carlactone, the substrate of MAX1, and methyl carlactonoate (MeCLA), a product downstream of MAX1. Furthermore, lbo mutants contained increased amounts of these compounds, and the LBO protein specifically converts MeCLA to an unidentified strigolactone-like compound. Thus, LBO function may be important in the later steps of strigolactone biosynthesis to inhibit shoot branching in Arabidopsis and other seed plants. PMID- 27194727 TI - The caspase-8 inhibitor emricasan combines with the SMAC mimetic birinapant to induce necroptosis and treat acute myeloid leukemia. AB - Resistance to chemotherapy is a major problem in cancer treatment, and it is frequently associated with failure of tumor cells to undergo apoptosis. Birinapant, a clinical SMAC mimetic, had been designed to mimic the interaction between inhibitor of apoptosis proteins (IAPs) and SMAC/Diablo, thereby relieving IAP-mediated caspase inhibition and promoting apoptosis of cancer cells. We show that acute myeloid leukemia (AML) cells are sensitive to birinapant-induced death and that the clinical caspase inhibitor emricasan/IDN-6556 augments, rather than prevents, killing by birinapant. Deletion of caspase-8 sensitized AML to birinapant, whereas combined loss of caspase-8 and the necroptosis effector MLKL (mixed lineage kinase domain-like) prevented birinapant/IDN-6556-induced death, showing that inhibition of caspase-8 sensitizes AML cells to birinapant-induced necroptosis. However, loss of MLKL alone did not prevent a caspase-dependent birinapant/IDN-6556-induced death, implying that AML will be less likely to acquire resistance to this drug combination. A therapeutic breakthrough in AML has eluded researchers for decades. Demonstrated antileukemic efficacy and safety of the birinapant/emricasan combination in vivo suggest that induction of necroptosis warrants clinical investigation as a therapeutic opportunity in AML. PMID- 27194728 TI - Activation of concurrent apoptosis and necroptosis by SMAC mimetics for the treatment of refractory and relapsed ALL. AB - More precise treatment strategies are urgently needed to decrease toxicity and improve outcomes for treatment-refractory leukemia. We used ex vivo drug response profiling of high-risk, relapsed, or refractory acute lymphoblastic leukemia (ALL) cases and identified a subset with exquisite sensitivity to small-molecule mimetics of the second mitochondria-derived activator of caspases (SMAC) protein. Potent ex vivo activity of the SMAC mimetic (SM) birinapant correlated with marked in vivo antileukemic effects, as indicated by delayed engraftment, decreased leukemia burden, and prolonged survival of xenografted mice. Antileukemic activity was dependent on simultaneous execution of apoptosis and necroptosis, as demonstrated by functional genomic dissection with a multicolored lentiCRISPR approach to simultaneously disrupt multiple genes in patient-derived ALL. SM specifically targeted receptor-interacting protein kinase 1 (RIP1) dependent death, and CRISPR-mediated disruption of RIP1 completely blocked SM induced death yet had no impact on the response to standard antileukemic agents. Thus, SM compounds such as birinapant circumvent escape from apoptosis in leukemia by activating a potent dual RIP1-dependent apoptotic and necroptotic cell death, which is not exploited by current therapy. Ex vivo drug activity profiling could provide important functional diagnostic information to identify patients who may benefit from targeted treatment with birinapant in early clinical trials. PMID- 27194730 TI - Host resistance to intranasal Acinetobacter baumannii reinfection in mice. AB - Acinetobacter baumannii is a major causative agent of healthcare-associated infection and develops multidrug resistance rapidly. However, little is known in the host defense mechanisms against this infection. In this study, we examined if mice recovered from a previous intranasal A. baumannii infection (recovered mice) are fully protected against a subsequent reinfection. We found that, despite the presence of specific serum IgG and mucosal IgA responses prior to the reinfection, the recovered mice were only marginally better protected against intranasal challenge with low doses of homologous or heterologous A. baumannii strains than the naive mice. Post-challenge immune and inflammatory (cells and cytokines) responses were generally comparable between recovered and naive mice although the recovered mice produced significantly higher amounts of IFN-gamma and IL-17 and had higher percentages and numbers of resident lung CD44(hi)CD62L( )CD4(+) and CD19(+) B lymphocytes. Taken together, our results suggest that mice recovered from a previous A. baumannii infection remain susceptible to reinfection, indicating the complexity of immune protection mechanism for this Gram-negative, multidrug-resistant emerging pathogen. PMID- 27194731 TI - Adaptive response of broilers to dietary phosphorus and calcium restrictions. AB - The aim of this study was to evaluate the capacity of chickens to adapt to and compensate for early dietary restriction of non-phytate P ( NPP: ) and/or Ca (10 to 21 d) in a later phase (22 to 35 d), and to determine whether compensatory processes depend on the P and Ca concentrations in the finisher diet. Four diets were formulated and fed to broilers from 10 to 21 d in order to generate birds with different mineral status: L1 (0.6% Ca, 0.30% NPP), L2 (0.6% Ca, 0.45% NPP), H1 (1.0% Ca, 0.30% NPP), and H2 (1.0% Ca, 0.45% NPP). On d 22, each group was divided into three groups which received a low (L, 0.48% Ca, 0.24% NPP), moderate (M, 0.70% Ca, 0.35% NPP), or high (H, 0.90% Ca, 0.35% NPP) finisher diet until 35 d, resulting in a total of 12 treatments. Lowering the Ca level enhanced apparent ileal digestibility of P (P AID) at 21 d especially with the high NPP level (Ca * NPP, P < 0.01). The lower bone mineralization observed at 21 d in broilers fed the L1 diet compared to those fed the H2 diet had disappeared by 35 d with long term stimulation of the P AID with the low NPP level (P < 0.001). Although P AID and growth performance were improved in birds fed the L1L compared to the L1H and H2H treatments, tibia characteristics tended to be lower in birds fed the L1L compared to those fed the L1H treatment. Birds fed the H1M treatment had higher P AID, growth performance and tibia ash content than those fed the H1H treatment. A significant increase in the mRNA levels of several genes encoding Ca and P transporters was observed at 35 d in birds fed the L1 followed by the L diet compared to birds fed the L1 followed by the M diet. In conclusion, chickens are able to adapt to early dietary changes in P and Ca through improvement of digestive efficiency in a later phase, and the extent of the compensation in terms of growth performance and bone mineralization depends on the P and Ca levels in the subsequent diet. PMID- 27194732 TI - Effects of development and delayed feed access on ghrelin expression in neonatal broiler chickens. AB - Two experiments were conducted to study the effects of development and delayed feed access on ghrelin expression in neonatal chickens. In experiment 1, ghrelin levels in ad libitum-fed chickens were assessed from hatching (0 h) to 120 h. Ghrelin mRNA expression increased after hatching and reached peak levels at 24 h; levels were 1.8-fold higher compared to those at 0 h. Afterward, ghrelin expression decreased consistently throughout the later experimental period, and at 120 h, it was only 16.0% of 0 h levels. The density of ghrelin immunopositive cells in the proventriculus and plasma ghrelin levels decreased slightly from hatching to 48 h and later increased slowly until the end of the experimental period. In a follow-up study, chickens were assigned randomly into 2 groups after hatching, a control group ( C: , fed ad libitum) and a delayed feeding group ( F+SF: , 72-h fast period, subsequently fed ad libitum). Delayed feed access for 72 h up-regulated ghrelin mRNA expression significantly in the proventriculus (P < 0.05) to 2.1-fold higher levels compared to the control, while the density of ghrelin immunopositive cells and the plasma ghrelin level decreased (P < 0.05) to 28.4% and 64.8% of the control, respectively. After the onset of feeding, the ghrelin mRNA expression in the delayed feeding group was decreased but still higher than that of the control (P < 0.05). The density of ghrelin immunopositive cells and the plasma ghrelin level climbed quickly and all returned to the control level with a supply of food for 48 h. These results suggest that the onset of feeding in neonatal chickens stimulated an increase in ghrelin peptide levels and that ghrelin peptide levels increased with age. Neonatal chickens respond to food deprivation in a different way than do young and adult chickens. PMID- 27194733 TI - Review: Effects of different growth rates in broiler breeder and layer hens on some productive traits. AB - Genetic selection that has been carried out for several dozen years has led to significant progress in poultry production by improving productive traits and increasing the profitability of broiler breeder and layer hen production. After hatching, broilers and layers differ mainly in feed intake, growth rate, efficiency of nutrient utilization, and development of muscles and adipose tissue. A key role can be played by hormonal mechanisms of appetite control in broilers and layers. The paper discusses the consequences of different growth rates resulting from long-term genetic selection on feed intake, efficiency of nutrient utilization, and development of muscles and adipose tissue, with particular consideration of the hormonal mechanisms of appetite control in broilers and layers. The information presented in this review paper shows that it would be worth comparing these issues in a meta-analysis. PMID- 27194729 TI - Increased GVHD-related mortality with broad-spectrum antibiotic use after allogeneic hematopoietic stem cell transplantation in human patients and mice. AB - Intestinal bacteria may modulate the risk of infection and graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo HSCT). Allo-HSCT recipients often develop neutropenic fever, which is treated with antibiotics that may target anaerobic bacteria in the gut. We retrospectively examined 857 allo-HSCT recipients and found that treatment of neutropenic fever with imipenem-cilastatin and piperacillin-tazobactam antibiotics was associated with increased GVHD-related mortality at 5 years (21.5% for imipenem-cilastatin-treated patients versus 13.1% for untreated patients, P = 0.025; 19.8% for piperacillin-tazobactam-treated patients versus 11.9% for untreated patients, P = 0.007). However, two other antibiotics also used to treat neutropenic fever, aztreonam and cefepime, were not associated with GVHD-related mortality (P = 0.78 and P = 0.98, respectively). Analysis of stool specimens from allo-HSCT recipients showed that piperacillin-tazobactam administration was associated with perturbation of gut microbial composition. Studies in mice demonstrated aggravated GVHD mortality with imipenem-cilastatin or piperacillin-tazobactam compared to aztreonam (P < 0.01 and P < 0.05, respectively). We found pathological evidence for increased GVHD in the colon of imipenem-cilastatin-treated mice (P < 0.05), but no difference in the concentration of short-chain fatty acids or numbers of regulatory T cells. Notably, imipenem-cilastatin treatment of mice with GVHD led to loss of the protective mucus lining of the colon (P < 0.01) and the compromising of intestinal barrier function (P < 0.05). Sequencing of mouse stool specimens showed an increase in Akkermansia muciniphila (P < 0.001), a commensal bacterium with mucus-degrading capabilities, raising the possibility that mucus degradation may contribute to murine GVHD. We demonstrate an underappreciated risk for the treatment of allo-HSCT recipients with antibiotics that may exacerbate GVHD in the colon. PMID- 27194734 TI - Allelic differences in a vacuolar invertase affect Arabidopsis growth at early plant development. AB - Improving carbon fixation in order to enhance crop yield is a major goal in plant sciences. By quantitative trait locus (QTL) mapping, it has been demonstrated that a vacuolar invertase (vac-Inv) plays a key role in determining the radical length in Arabidopsis. In this model, variation in vac-Inv activity was detected in a near isogenic line (NIL) population derived from a cross between two divergent accessions: Landsberg erecta (Ler) and Cape Verde Island (CVI), with the CVI allele conferring both higher Inv activity and longer radicles. The aim of the current work is to understand the mechanism(s) underlying this QTL by analyzing structural and functional differences of vac-Inv from both accessions. Relative transcript abundance analyzed by quantitative real-time PCR (qRT-PCR) showed similar expression patterns in both accessions; however, DNA sequence analyses revealed several polymorphisms that lead to changes in the corresponding protein sequence. Moreover, activity assays revealed higher vac-Inv activity in genotypes carrying the CVI allele than in those carrying the Ler allele. Analyses of purified recombinant proteins showed a similar K m for both alleles and a slightly higher V max for that of Ler. Treatment of plant extracts with foaming to release possible interacting Inv inhibitory protein(s) led to a large increase in activity for the Ler allele, but no changes for genotypes carrying the CVI allele. qRT-PCR analyses of two vac-Inv inhibitors in seedlings from parental and NIL genotypes revealed different expression patterns. Taken together, these results demonstrate that the vac-Inv QTL affects root biomass accumulation and also carbon partitioning through a differential regulation of vac-Inv inhibitors at the mRNA level. PMID- 27194735 TI - Identification and localization of bioactive naphthoquinones in the roots and rhizosphere of Paterson's curse (Echium plantagineum), a noxious invader. AB - Bioactive plant secondary products are frequently the drivers of complex rhizosphere interactions, including those with other plants, herbivores and microbiota. These chemically diverse molecules typically accumulate in a highly regulated manner in specialized plant tissues and organelles. We studied the production and localization of bioactive naphthoquinones (NQs) in the roots of Echium plantagineum, an invasive endemic weed in Australia. Roots of E. plantagineum produced red-coloured NQs in the periderm of primary and secondary roots, while seedling root hairs exuded NQs in copious quantities. Confocal imaging and microspectrofluorimetry confirmed that bioactive NQs were deposited in the outer layer of periderm cells in mature roots, resulting in red colouration. Intracellular examination revealed that periderm cells contained numerous small red vesicles for storage and intracellular transport of shikonins, followed by subsequent extracellular deposition. Periderm and root hair extracts of field- and phytotron-grown plants were analysed by UHPLC/Q-ToF MS (ultra high pressure liquid chromatography coupled to quadrupole time of flight mass spectrometry) and contained more than nine individual NQs, with dimethylacrylshikonin, and phytotoxic shikonin, deoxyshikonin and acetylshikonin predominating. In seedlings, shikonins were first found 48h following germination in the root-hypocotyl junction, as well as in root hair exudates. In contrast, the root cortices of both seedling and mature root tissues were devoid of NQs. SPRE (solid phase root zone extraction) microprobes strategically placed in soil surrounding living E. plantagineum plants successfully extracted significant levels of bioactive shikonins from living roots, rhizosphere and bulk soil surrounding roots. These findings suggest important roles for accumulation of shikonins in the root periderm and subsequent rhizodeposition in plant defence, interference, and invasion success. PMID- 27194736 TI - WAX INDUCER1 (HvWIN1) transcription factor regulates free fatty acid biosynthetic genes to reinforce cuticle to resist Fusarium head blight in barley spikelets. AB - Fusarium head blight (FHB), caused by Fusarium graminearum, is one of the most devastating diseases of wheat and barley. Resistance to FHB is highly complex and quantitative in nature, and is most often classified as resistance to spikelet infection and resistance to spread of pathogen through the rachis. In the present study, a resistant (CI9831) and a susceptible (H106-371) two-row barley genotypes, with contrasting levels of spikelet resistance to FHB, pathogen or mock-inoculated, were profiled for metabolites based on liquid chromatography and high resolution mass spectrometry. The key resistance-related (RR) metabolites belonging to fatty acids, phenylpropanoids, flavonoids and terpenoid biosynthetic pathways were identified. The free fatty acids (FFAs) linoleic and palmitic acids were among the highest fold change RR induced (RRI) metabolites. These FFAs are deposited as cutin monomers and oligomers to reinforce the cuticle, which acts as a barrier to pathogen entry. Quantitative real-time PCR studies revealed higher expressions of KAS2, CYP86A2, CYP89A2, LACS2 and WAX INDUCER1 (HvWIN1) transcription factor in the pathogen-inoculated resistant genotype than in the susceptible genotype. Knockdown of HvWIN1 by virus-induced genes silencing (VIGS) in resistant genotype upon pathogen inoculation increased the disease severity and fungal biomass, and decreased the abundance of FFAs like linoleic and palmitic acids. Notably, the expression of CYP86A2, CYP89A2 and LAC2 genes was also suppressed, proving the link of HvWIN1 in regulating these genes in cuticle biosynthesis as a defense response. PMID- 27194737 TI - CitAP2.10 activation of the terpene synthase CsTPS1 is associated with the synthesis of (+)-valencene in 'Newhall' orange. AB - Aroma is a vital characteristic that determines the quality and commercial value of citrus fruits, and characteristic volatiles have been analyzed in different citrus species. In sweet orange, Citrus sinensis, the sesquiterpene (+)-valencene is a key volatile compound in the fruit peel. Valencene synthesis is catalyzed by the terpene synthase CsTPS1, but the transcriptional mechanisms controlling its gene expression are unknown. Here, the AP2/ERF (APETALA2/ethylene response factor) transcription factor, CitAP2.10, is characterized as a regulator of (+) valencene synthesis. The expression pattern of CitAP2.10 was positively correlated with (+)-valencene content and CsTPS1 expression. Dual-luciferase assays indicated that CitAP2.10 could trans-activate the CsTPS1 promoter. Ethylene enhanced expression of CitAP2.10 and this effect was abolished by the ethylene antagonist 1-methylcyclopropene. The role and function of CitAP2.10 in (+)-valencene biosynthesis were confirmed using the Arabidopsis homolog (AtWRI1), which also transiently activated the CsTPS1 promoter. Furthermore, transient over expression of CitAP2.10 triggered (+)-valencene biosynthesis in sweet orange fruit. These results indicate that CitAP2.10 regulates (+)-valencene synthesis via induction of CsTPS1 mRNA accumulation. PMID- 27194738 TI - Characterization of purple acid phosphatases involved in extracellular dNTP utilization in Stylosanthes. AB - Stylo (Stylosanthes spp.) is a pasture legume predominant in tropical and subtropical areas, where low phosphorus (P) availability is a major constraint for plant growth. Therefore, stylo might exhibit superior utilization of the P pool on acid soils, particularly organic P. However, little is known about mechanisms of inorganic phosphate (Pi) acquisition employed by stylo. In this study, the utilization of extracellular deoxy-ribonucleotide triphosphate (dNTP) and the underlying physiological and molecular mechanisms were examined for two stylo genotypes with contrasting P efficiency. Results showed that the P efficient genotype, TPRC2001-1, was superior to the P-inefficient genotype, Fine stem, when using dNTP as the sole P source. This was reflected by a higher dry weight and total P content for TPRC2001-1 than for Fine-stem, which was correlated with higher root-associated acid phosphatase (APase) activities in TPRC2001-1 under low P conditions. Subsequently, three PAP members were cloned from TPRC2001-1: SgPAP7, SgPAP10, and SgPAP26 Expression levels of these three SgPAPs were up-regulated by Pi starvation in stylo roots. Furthermore, there was a higher abundance of transcripts of SgPAP7 and SgPAP10 in TPRC2001-1 than in Fine-stem. Subcellular localization analysis demonstrated that these three SgPAPs were localized on the plasma membrane. Overexpression of these three SgPAPs could result in significantly increased root-associated APase activities, and thus extracellular dNTP utilization in bean hairy roots. Taken together, the results herein suggest that SgPAP7, SgPAP10, and SgPAP26 may differentially contribute to root-associated APase activities, and thus control extracellular dNTP utilization in stylo. PMID- 27194739 TI - New insights into the post-translational modification of multiple phosphoenolpyruvate carboxylase isoenzymes by phosphorylation and monoubiquitination during sorghum seed development and germination. AB - Phosphoenolpyruvate carboxylase (PEPC; E.C. 4.1.1.31) was characterized in developing and germinating sorghum seeds, focusing on the transcript and polypeptide abundance of multiple plant-type phosphoenolpyruvate carboxylase (PTPC) genes, and the post-translational modification of each isoenzyme by phosphorylation versus monoubiquitination during germination. We observed high levels of SbPPC4 (Sb07g014960) transcripts during early development (stage I), and extensive transcript abundance of SbPPC2 (Sb02g021090) and SbPPC3 (Sb04g008720) throughout the entire life cycle of the seed. Although tandem mass spectrometry (MS) analysis of immunopurified PTPC indicated that four different PTPC isoenzymes were expressed in the developing and germinating seeds, SbPPC3 was the most abundant isozyme of the developing seed, and of the embryo and the aleurone layer of germinating seeds. In vivo phosphorylation of the different PTPC isoenzymes at their conserved N-terminal seryl phosphorylation site during germination was also established by MS/MS analysis. Furthermore, three of the four isoenzymes were partially monoubiquitinated, with MS/MS pinpointing SbPPC2 and SbPPC3 monoubiquitination at the conserved Lys-630 and Lys-624 residues, respectively. Our results demonstrate that monoubiquitination and phosphorylation simultaneously occur in vivo with different PTPC isozymes during seed germination. In addition, we show that PTPC monoubiquitination in germinating sorghum seeds always increases at stage II (emergence of the radicle), is maintained during the aerobic period of rapid cell division and reserve mobilization, and remains relatively constant until stage IV-V when coleoptiles initiate the formation of the photosynthetic tissues. PMID- 27194740 TI - Tissue-specific laser microdissection of the Brassica napus funiculus improves gene discovery and spatial identification of biological processes. AB - The three primary tissue systems of the funiculus each undergo unique developmental programs to support the growth and development of the filial seed. To understand the underlying transcriptional mechanisms that orchestrate development of the funiculus at the globular embryonic stage of seed development, we used laser microdissection coupled with RNA-sequencing to produce a high resolution dataset of the mRNAs present in the epidermis, cortex, and vasculature of the Brassica napus (canola) funiculus. We identified 7761 additional genes in these tissues compared with the whole funiculus organ alone using this technology. Differential expression and enrichment analyses were used to identify several biological processes associated with each tissue system. Our data show that cell wall modification and lipid metabolism are prominent in the epidermis, cell growth and modification occur in the cortex, and vascular tissue proliferation and differentiation occur in the central vascular strand. We provide further evidence that each of the three tissue systems of the globular stage funiculus are involved in specific biological processes that all co ordinate to support seed development. The identification of genes and gene regulators responsible for tissue-specific developmental processes of the canola funiculus now serves as a valuable resource for seed improvement research. PMID- 27194741 TI - The alpha-subunit of the rice heterotrimeric G protein, RGA1, regulates drought tolerance during the vegetative phase in the dwarf rice mutant d1. AB - Essential in the Green Revolution was the development of high-yielding dwarf varieties of rice (Oryza sativa L.), but their selection was not based on responses to water limitation. We studied physiological responses to progressive drought of the dwarf rice mutant, d1, in which the RGA1 gene, which encodes the GTP-binding alpha-subunit of the heterotrimeric G protein, is non-functional. Wild-type (WT) plants cease net carbon fixation 11 days after water is withheld, while d1 plants maintain net photosynthesis for an additional week. During drought, d1 plants exhibit greater stomatal conductance than the WT, but both genotypes exhibit the same transpirational water loss per unit leaf area. This is explained by a smaller driving force for water loss in d1 owing to its lower leaf temperatures, consistent with its more erect architecture. As drought becomes more severe, WT plants show an accelerated decline in photosynthesis, which may be exacerbated by the higher leaf temperatures in the WT. We thus show how a rice mutant with dwarf and erect leaves has a decreased susceptibility to water stress. Accordingly, it may be useful to incorporate RGA1 mutation in breeding or biotechnological strategies for development of drought-resistant rice. PMID- 27194742 TI - The grapevine VvibZIPC22 transcription factor is involved in the regulation of flavonoid biosynthesis. AB - In grapevine, flavonoids constitute one of the most abundant subgroups of secondary metabolites, influencing the quality, health value, and typicity of wines. Their synthesis in many plant species is mainly regulated at the transcriptional level by modulation of flavonoid pathway genes either by single regulators or by complexes of different regulators. In particular, bZIP and MYB factors interact synergistically in the recognition of light response units present in the promoter of some genes of the pathway, thus mediating light dependent flavonoid biosynthesis. We recently identified VvibZIPC22, a member of clade C of the grapevine bZIP family, in a quantitative trait locus (QTL) specifically associated with kaemperol content in mature berries. Here, to validate the involvement of this candidate gene in the fine regulation of flavonol biosynthesis, we characterized its function by in vitro and in vivo experiments. A role for this gene in the control of flavonol biosynthesis was indeed confirmed by its highest expression at flowering and during UV light mediated induction, paralleled by accumulation of the flavonol synthase 1 transcript and flavonol compounds. The overexpression of VvibZIPC22 in tobacco caused a significant increase in several flavonoids in the flower, via induction of general and specific genes of the pathway. In agreement with this evidence, VvibZIPC22 was able to activate the promoters of specific genes of the flavonoid pathway, alone or together with other factors, as revealed by transient reporter assays. These findings, supported by in silico indications, allowed us to propose VvibZIPC22 as a new regulator of flavonoid biosynthesis in grapevine. PMID- 27194743 TI - Embryological Origin of Human Smooth Muscle Cells Influences Their Ability to Support Endothelial Network Formation. AB - Vascular smooth muscle cells (SMCs) from distinct anatomic locations derive from different embryonic origins. Here we investigated the respective potential of different embryonic origin-specific SMCs derived from human embryonic stem cells (hESCs) to support endothelial network formation in vitro. SMCs of three distinct embryological origins were derived from an mStrawberry-expressing hESC line and were cocultured with green fluorescent protein-expressing human umbilical vein endothelial cells (HUVECs) to investigate the effects of distinct SMC subtypes on endothelial network formation. Quantitative analysis demonstrated that lateral mesoderm (LM)-derived SMCs best supported HUVEC network complexity and survival in three-dimensional coculture in Matrigel. The effects of the LM-derived SMCs on HUVECs were at least in part paracrine in nature. A TaqMan array was performed to identify the possible mediators responsible for the differential effects of the SMC lineages, and a microarray was used to determine lineage-specific angiogenesis gene signatures. Midkine (MDK) was identified as one important mediator for the enhanced vasculogenic potency of LM-derived SMCs. The functional effects of MDK on endothelial network formation were then determined by small interfering RNA-mediated knockdown in SMCs, which resulted in impaired network complexity and survival of LM-derived SMC cocultures. The present study is the first to show that SMCs from distinct embryonic origins differ in their ability to support HUVEC network formation. LM-derived SMCs best supported endothelial cell network complexity and survival in vitro, in part through increased expression of MDK. A lineage-specific approach might be beneficial for vascular tissue engineering and therapeutic revascularization. SIGNIFICANCE: Mural cells are essential for the stabilization and maturation of new endothelial cell networks. However, relatively little is known of the effect of the developmental origins of mural cells on their signaling to endothelial cells and how this affects vessel development. The present study demonstrated that human smooth muscle cells (SMCs) from distinct embryonic origins differ in their ability to support endothelial network formation. Lateral mesoderm-derived SMCs best support endothelial cell network complexity and survival in vitro, in part through increased expression of midkine. A lineage-specific approach might be beneficial for vascular tissue engineering and therapeutic revascularization. PMID- 27194744 TI - Grafted Subventricular Zone Neural Stem Cells Display Robust Engraftment and Similar Differentiation Properties and Form New Neurogenic Niches in the Young and Aged Hippocampus. AB - : As clinical application of neural stem cell (NSC) grafting into the brain would also encompass aged people, critical evaluation of engraftment of NSC graft derived cells in the aged hippocampus has significance. We examined the engraftment and differentiation of alkaline phosphatase-positive NSCs expanded from the postnatal subventricular zone (SVZ), 3 months after grafting into the intact young or aged rat hippocampus. Graft-derived cells engrafted robustly into both young and aged hippocampi. Although most graft-derived cells pervasively migrated into different hippocampal layers, the graft cores endured and contained graft-derived neurons expressing neuron-specific nuclear antigen (NeuN) and gamma amino butyric acid in both groups. A fraction of migrated graft-derived cells in the neurogenic subgranular zone-granule cell layer also expressed NeuN. Neuronal differentiation was, however, occasionally seen amid graft-derived cells that had migrated into non-neurogenic regions, where substantial fractions differentiated into S-100beta+ astrocytes, NG2+ oligodendrocyte progenitors, or Olig2+ putative oligodendrocytes. In both age groups, graft cores located in non-neurogenic regions displayed many doublecortin-positive (DCX+) immature neurons at 3 months after grafting. Analyses of cells within graft cores using birth dating and putative NSC markers revealed that DCX+ neurons were newly born neurons derived from engrafted cells and that putative NSCs persisted within the graft cores. Thus, both young and aged hippocampi support robust engraftment and similar differentiation of SVZ-NSC graft-derived cells. Furthermore, some grafted NSCs retain the "stemness" feature and produce new neurons even at 3 months after grafting, implying that grafting of SVZ-NSCs into the young or aged hippocampus leads to establishment of new neurogenic niches in non-neurogenic regions. SIGNIFICANCE: The results demonstrate that advanced age of the host at the time of grafting has no major adverse effects on engraftment, migration, and differentiation of grafted subventricular zone-neural stem cells (SVZ-NSCs) in the intact hippocampus, as both young and aged hippocampi promoted excellent engraftment, migration, and differentiation of SVZ-NSC graft-derived cells in the present study. Furthermore, SVZ-NSC grafts showed ability for establishing neurogenic niches in non-neurogenic regions, generating new neurons for extended periods after grafting. This phenomenon will be beneficial if these niches can continuously generate new neurons and glia in the grafted hippocampus, as newly generated neurons and glia are expected to improve, not only the microenvironment, but also the plasticity and function of the aged hippocampus. Overall, these results have significance because the potential application of NSC grafting for treatment of neurodegenerative disorders at early stages of disease progression and age-related impairments would mostly involve aged persons as recipients. PMID- 27194746 TI - Overnutrition, ectopic lipid and the metabolic syndrome. AB - The metabolic syndrome is a constellation of metabolic risk factors including atherogenic dyslipidemia (elevated serum triglycerides, reduced high-density lipoprotein (HDL) cholesterol), elevated blood pressure, dysglycemia (insulin resistance and elevated serum glucose), a pro-inflammatory state, and a prothrombotic state. Most persons with metabolic syndrome are obese, and usually have abdominal obesity. Generally, obesity is a reflection of overnutrition. A current view is that when adipose tissue fails to store all excess nutrients as triglyceride, lipid begins to accumulate in various tissues (eg, muscle, liver, pancreas, and heart). This accumulation is called ectopic lipid. Various mechanisms have been proposed whereby ectopic lipid is detrimental in different tissues; these derangements induce metabolic risk factors. The foundation of the metabolic syndrome thus appears to be overnutrition, that is, more nutrient intake than can be safely disposed by lipid oxidation. Excess dietary carbohydrate also induces ectopic lipid. Of interest, less than half of obese individuals develop metabolic syndrome. Through various mechanisms they adapt to overnutrition so as to minimize lipid overload in tissues, and consequently, prevent the syndrome. PMID- 27194745 TI - Epigenetic Library Screen Identifies Abexinostat as Novel Regulator of Adipocytic and Osteoblastic Differentiation of Human Skeletal (Mesenchymal) Stem Cells. AB - : The epigenetic mechanisms promoting lineage-specific commitment of human skeletal (mesenchymal or stromal) stem cells (hMSCs) into adipocytes or osteoblasts are still not fully understood. Herein, we performed an epigenetic library functional screen and identified several novel compounds, including abexinostat, which promoted adipocytic and osteoblastic differentiation of hMSCs. Using gene expression microarrays, chromatin immunoprecipitation for H3K9Ac combined with high-throughput DNA sequencing (ChIP-seq), and bioinformatics, we identified several key genes involved in regulating stem cell proliferation and differentiation that were targeted by abexinostat. Concordantly, ChIP quantitative polymerase chain reaction revealed marked increase in H3K9Ac epigenetic mark on the promoter region of AdipoQ, FABP4, PPARgamma, KLF15, CEBPA, SP7, and ALPL in abexinostat-treated hMSCs. Pharmacological inhibition of focal adhesion kinase (PF-573228) or insulin-like growth factor-1R/insulin receptor (NVP-AEW51) signaling exhibited significant inhibition of abexinostat-mediated adipocytic differentiation, whereas inhibition of WNT (XAV939) or transforming growth factor-beta (SB505124) signaling abrogated abexinostat-mediated osteogenic differentiation of hMSCs. Our findings provide insight into the understanding of the relationship between the epigenetic effect of histone deacetylase inhibitors, transcription factors, and differentiation pathways governing adipocyte and osteoblast differentiation. Manipulating such pathways allows a novel use for epigenetic compounds in hMSC-based therapies and tissue engineering. SIGNIFICANCE: This unbiased epigenetic library functional screen identified several novel compounds, including abexinostat, that promoted adipocytic and osteoblastic differentiation of human skeletal (mesenchymal or stromal) stem cells (hMSCs). These data provide new insight into the understanding of the relationship between the epigenetic effect of histone deacetylase inhibitors, transcription factors, and differentiation pathways controlling adipocyte and osteoblast differentiation of hMSCs. Manipulating such pathways allows a novel use for epigenetic compounds in hMSC-based therapies for tissue engineering, bone disease, obesity, and metabolic-disorders. PMID- 27194747 TI - Faecal eosinophil cationic protein and serum immunoglobulin E in relation to infant feeding practices. AB - Background To date, the effects of exclusive breastfeeding duration and timing of solid food introduction on allergy prevention are unclear. The aim of this study was to determine the effect of variable feeding practices on intestinal inflammation in infants using faecal eosinophil cationic protein as a surrogate marker and to assess whether faecal eosinophil cationic protein is associated with serum immunoglobulin E. Methods Subjects ( n = 206) were enrolled from the Prediction of Allergies in Taiwanese CHildren (PATCH) birth cohort study. Stool samples were collected at 6 and 12 months for determining eosinophil cationic protein, and blood was collected for determining total and allergen-specific immunoglobulin E at 12 months. We compared these biomarkers between infants with variable exclusive breastfeeding duration and infants introduced to solid foods at various periods. The association between faecal eosinophil cationic protein, total serum immunoglobulin E and specific immunoglobulin E was also analysed. Results Faecal eosinophil cationic protein was significantly higher in exclusively breastfed infants compared with formula-fed infants and infants who were not exclusively breastfed at 6 months of age ( P < 0.05). At 12 months, infants who were introduced to solid foods at 5-6 months had the lowest faecal eosinophil cationic protein compared with those who were introduced at earlier and later periods. There was no significant association between faecal eosinophil cationic protein and serum immunoglobulin E. Conclusion We found that breastfeeding exclusively for >6 months did not reduce serum immunoglobulin E, but rather increased intestinal inflammation. Faecal eosinophil cationic protein was not associated with total serum immunoglobulin E and specific immunoglobulin E and might not be a useful indictor of immunoglobulin E sensitization in infancy. PMID- 27194749 TI - Epistasis and the Dynamics of Reversion in Molecular Evolution. AB - Recent studies of protein evolution contend that the longer an amino acid substitution is present at a site, the less likely it is to revert to the amino acid previously occupying that site. Here we study this phenomenon of decreasing reversion rates rigorously and in a much more general context. We show that, under weak mutation and for arbitrary fitness landscapes, reversion rates decrease with time for any site that is involved in at least one epistatic interaction. Specifically, we prove that, at stationarity, the hazard function of the distribution of waiting times until reversion is strictly decreasing for any such site. Thus, in the presence of epistasis, the longer a particular character has been absent from a site, the less likely the site will revert to its prior state. We also explore several examples of this general result, which share a common pattern whereby the probability of having reverted increases rapidly at short times to some substantial value before becoming almost flat after a few substitutions at other sites. This pattern indicates a characteristic tendency for reversion to occur either almost immediately after the initial substitution or only after a very long time. PMID- 27194748 TI - Retinal Axon Guidance Requires Integration of Eya and the Jak/Stat Pathway into Phosphotyrosine-Based Signaling Circuitries in Drosophila. AB - The transcriptional coactivator and phosphatase eyes absent (Eya) is dynamically compartmentalized between the nucleus and cytoplasm. Although the nuclear transcriptional circuits within which Eya operates have been extensively characterized, understanding of its cytoplasmic functions and interactions remains limited. Our previous work showed that phosphorylation of Drosophila Eya by the Abelson tyrosine kinase can recruit Eya to the cytoplasm and that eya abelson interactions are required for photoreceptor axons to project to correct layers in the brain. Based on these observations, we postulated that photoreceptor axon targeting might provide a suitable context for identifying the cytoplasmic signaling cascades with which Eya interacts. Using a dose-sensitive eya misexpression background, we performed an RNA interference-based genetic screen to identify suppressors. Included among the top 10 hits were nonreceptor tyrosine kinases and multiple members of the Jak/Stat signaling network (hop, Stat92E, Socs36E, and Socs44A), a pathway not previously implicated in axon targeting. Individual loss-of-function phenotypes combined with analysis of axonal projections in Stat92E null clones confirmed the importance of photoreceptor autonomous Jak/Stat signaling. Experiments in cultured cells detected cytoplasmic complexes between Eya and Hop, Socs36E and Socs44A; the latter interaction required both the Src homology 2 motif in Socs44A and tyrosine phosphorylated Eya, suggesting direct binding and validating the premise of the screen. Taken together, our data provide new insight into the cytoplasmic phosphotyrosine signaling networks that operate during photoreceptor axon guidance and suggest specific points of interaction with Eya. PMID- 27194753 TI - Social Participation and Cognitive Decline Among Community-dwelling Older Adults: A Community-based Longitudinal Study. AB - Objective: To examine whether social participation (SP) by older individuals is associated with cognitive decline (CD). Method: Participants were community dwelling older adults aged 65 or older with both independent activities of daily living and normal cognitive performance at baseline (2,768 men and 3,325 women). CD was evaluated using the Cognitive Performance Scale. Logistic regression analysis stratified by gender was used to examine CD in relation to SP, with nonparticipation as reference. Age, family, body mass index, pensions, comorbidities, medications, alcohol, smoking, depression, self-rated health, and instrumental activities of daily living were used as covariates. Results: During the 3-year follow-up, 16.7% of eligible participants reported CD. After covariate adjustments, greater social group participation was associated with CD prevention for women only. Lessened negative CD effects were found in respondents active in these particular types of social outlets: neighborhood associations (odds ratio = 0.81, 95% confidence interval = 0.66-0.99) and local event groups (0.79, 0.63 0.99) for men, and hobby groups (0.70, 0.54-0.91) and volunteer groups (0.66, 0.45-0.96) for women. Discussion: Our results suggest that greater social group participation prevents CD in women, while the beneficial effect of each type of SP on cognition differs between genders. Determining which types of social groups are best for community-dwelling older people's participation based on gender may help them maintain their cognitive functioning abilities. PMID- 27194751 TI - Novel Intronic RNA Structures Contribute to Maintenance of Phenotype in Saccharomyces cerevisiae. AB - The Saccharomyces cerevisiae genome has undergone extensive intron loss during its evolutionary history. It has been suggested that the few remaining introns (in only 5% of protein-coding genes) are retained because of their impact on function under stress conditions. Here, we explore the possibility that novel noncoding RNA structures (ncRNAs) are embedded within intronic sequences and are contributing to phenotype and intron retention in yeast. We employed de novo RNA structure prediction tools to screen intronic sequences in S. cerevisiae and 36 other fungi. We identified and validated 19 new intronic RNAs via RNA sequencing (RNA-seq) and RT-PCR. Contrary to the common belief that excised introns are rapidly degraded, we found that, in six cases, the excised introns were maintained intact in the cells. In another two cases we showed that the ncRNAs were further processed from their introns. RNA-seq analysis confirmed that introns in ribosomal protein genes are more highly expressed when they contain predicted RNA structures. We deleted the novel intronic RNA structure within the GLC7 intron and showed that this region, rather than the intron itself, is responsible for the cell's ability to respond to salt stress. We also showed a direct association between the in cis presence of the intronic RNA and GLC7 expression. Overall, these data support the notion that some introns may have been maintained in the genome because they harbor functional RNA structures. PMID- 27194750 TI - Heterozygote Advantage Is a Common Outcome of Adaptation in Saccharomyces cerevisiae. AB - Adaptation in diploids is predicted to proceed via mutations that are at least partially dominant in fitness. Recently, we argued that many adaptive mutations might also be commonly overdominant in fitness. Natural (directional) selection acting on overdominant mutations should drive them into the population but then, instead of bringing them to fixation, should maintain them as balanced polymorphisms via heterozygote advantage. If true, this would make adaptive evolution in sexual diploids differ drastically from that of haploids. The validity of this prediction has not yet been tested experimentally. Here, we performed four replicate evolutionary experiments with diploid yeast populations (Saccharomyces cerevisiae) growing in glucose-limited continuous cultures. We sequenced 24 evolved clones and identified initial adaptive mutations in all four chemostats. The first adaptive mutations in all four chemostats were three copy number variations, all of which proved to be overdominant in fitness. The fact that fitness overdominant mutations were always the first step in independent adaptive walks supports the prediction that heterozygote advantage can arise as a common outcome of directional selection in diploids and demonstrates that overdominance of de novo adaptive mutations in diploids is not rare. PMID- 27194754 TI - Carbon Dioxide Angiography. PMID- 27194752 TI - Buffering of Genetic Regulatory Networks in Drosophila melanogaster. AB - Regulatory variation in gene expression can be described by cis- and trans genetic components. Here we used RNA-seq data from a population panel of Drosophila melanogaster test crosses to compare allelic imbalance (AI) in female head tissue between mated and virgin flies, an environmental change known to affect transcription. Indeed, 3048 exons (1610 genes) are differentially expressed in this study. A Bayesian model for AI, with an intersection test, controls type I error. There are ~200 genes with AI exclusively in mated or virgin flies, indicating an environmental component of expression regulation. On average 34% of genes within a cross and 54% of all genes show evidence for genetic regulation of transcription. Nearly all differentially regulated genes are affected in cis, with an average of 63% of expression variation explained by the cis-effects. Trans-effects explain 8% of the variance in AI on average and the interaction between cis and trans explains an average of 11% of the total variance in AI. In both environments cis- and trans-effects are compensatory in their overall effect, with a negative association between cis- and trans-effects in 85% of the exons examined. We hypothesize that the gene expression level perturbed by cis-regulatory mutations is compensated through trans-regulatory mechanisms, e.g., trans and cis by trans-factors buffering cis-mutations. In addition, when AI is detected in both environments, cis-mated, cis-virgin, and trans-mated-trans-virgin estimates are highly concordant with 99% of all exons positively correlated with a median correlation of 0.83 for cis and 0.95 for trans We conclude that the gene regulatory networks (GRNs) are robust and that trans-buffering explains robustness. PMID- 27194755 TI - Rotarex Mechanical Debulking in Acute and Subacute Arterial Lesions. AB - INTRODUCTION: Data regarding the effectiveness and safety of percutaneous mechanical thrombectomy (PMT) in contemporary routine care are scarce. MATERIALS AND METHODS: Consecutive patients undergoing PMT of native lower limb acutely/subacutely occluded arteries were included. RESULTS: In all, 525 consecutive patients were available for analysis with a mean age of 66.7 +/- 10.7 years. Almost two-third (n = 324; 61.7%) were men with acutely (n = 211; 40.2%) or subacutely (n = 314; 59.8%) occluded lesions presenting mostly in Rutherford Becker category (RBC): 3 (30.3%) and 4 (47.6%). Mean lesion length was 159 mm (range 22-279 mm), with moderate and severe calcification in 119 (23.3%) lesions. PMT was performed solely in 161(27.2%), PMT + balloon angioplasty in 232 (39.1%), provisional stenting in 169 (28.4%), and thrombolysis in 77 (13.9%) interventions. Procedural technical success rate was 97.7%, with improvement in RBC persisting in 74.1% of patients after 12 +/- 2.4 months mean time follow-up. Overall 30 days major adverse events (MAEs) was 6.9% with a mortality rate of 1.1%. No death was directly related to the device. After 12 months, a promising overall target lesion revascularization (TLR; 10.1%), non-TLR (6.6%), and major amputation rates (2.3%) were found. One-year mortality was 8%. CONCLUSION: Treatment with PMT resulted in clinic and hemodynamic improvement in the majority of patients, thereby reducing the need for thrombolysis in a significant proportion of patients. Prospective studies in this issue are recommended. PMID- 27194757 TI - A Novel Open and Infectious Form of Echovirus 1. AB - One of the hallmarks of enterovirus genome delivery is the formation of an uncoating intermediate particle. Based on previous studies of mostly heated picornavirus particles, intermediate particles were shown to have externalized the innermost capsid protein (VP4) and exposed the N terminus of VP1 and to have reduced infectivity. Here, in addition to the native and intact particle type, we have identified another type of infectious echovirus 1 (E1) particle population during infection. Our results show that E1 is slightly altered during entry, which leads to the broadening of the major virion peak in the sucrose gradient. In contrast, CsCl gradient separation revealed that in addition to the light intact and empty particles, a dense particle peak appeared during infection in cells. When the broad peak from the sucrose gradient was subjected to a CsCl gradient, it revealed light and dense particles, further suggesting that the shoulder represents the dense particle. The dense particle was permeable to SYBR green II, it still contained most of its VP4, and it was able to bind to its receptor alpha2beta1 integrin and showed high infectivity. A thermal assay further showed that the alpha2beta1 integrin binding domain (I-domain) stabilized the virus particle. Finally, heating E1 particles to superphysiological temperatures produced more fragile particles with aberrant ultrastructural appearances, suggesting that they are distinct from the dense E1 particles. These results describe a more open and highly infectious E1 particle that is naturally produced during infection and may represent a novel form of an uncoating intermediate. IMPORTANCE: In this paper, we have characterized a possible uncoating intermediate particle of E1 that is produced in cells during infection. Before releasing their genome into the host cytosol, enteroviruses go through structural changes in their capsid, forming an uncoating intermediate particle. It was shown previously that structural changes can be induced by receptor interactions and, in addition, by heating the native virion to superphysiological temperatures. Here, we demonstrate that an altered, still infectious E1 particle is found during infection. This particle has a more open structure, and it cannot be formed by heating. It still contains the VP4 protein and is able to bind to its receptor and cause infection. Moreover, we show that in contrast to some other enteroviruses, the receptor-virion interaction has a stabilizing effect on E1. This paper highlights the differences between enterovirus species and further increases our understanding of various uncoating forms of enteroviruses. PMID- 27194756 TI - Transformation by Polyomavirus Middle T Antigen Involves a Unique Bimodal Interaction with the Hippo Effector YAP. AB - Murine polyomavirus has repeatedly provided insights into tumorigenesis, revealing key control mechanisms such as tyrosine phosphorylation and phosphoinositide 3-kinase (PI3K) signaling. We recently demonstrated that polyomavirus small T antigen (ST) binds YAP, a major effector of Hippo signaling, to regulate differentiation. Here we characterize YAP as a target of middle T antigen (MT) important for transformation. Through a surface including residues R103 and D182, wild-type MT binds to the YAP WW domains. Mutation of either R103 or D182 of MT abrogates YAP binding without affecting binding to other signaling molecules or the strength of PI3K or Ras signaling. Either genetic abrogation of YAP binding to MT or silencing of YAP via short hairpin RNA (shRNA) reduced MT transformation, suggesting that YAP makes a positive contribution to the transformed phenotype. MT targets YAP both by activating signaling pathways that affect it and by binding to it. MT signaling, whether from wild-type MT or the YAP-binding MT mutant, promoted YAP phosphorylation at S127 and S381/397 (YAP2/YAP1). Consistent with the known functions of these phosphorylated serines, MT signaling leads to the loss of YAP from the nucleus and degradation. Binding of YAP to MT brings it together with protein phosphatase 2A (PP2A), leading to the dephosphorylation of YAP in the MT complex. It also leads to the enrichment of YAP in membranes. Taken together, these results indicate that YAP promotes MT transformation via mechanisms that may depart from YAP's canonical oncogenic transcriptional activation functions. IMPORTANCE: The highly conserved Hippo/YAP pathway is important for tissue development and homeostasis. Increasingly, changes in this pathway are being associated with cancer. Middle T antigen (MT) is the primary polyomavirus oncogene responsible for tumor formation. In this study, we show that MT signaling promotes YAP phosphorylation, loss from the nucleus, and increased turnover. Notably, MT genetics demonstrate that YAP binding to MT is important for transformation. Because MT also binds PP2A, YAP bound to MT is dephosphorylated, stabilized, and localized to membranes. Taken together, these results indicate that YAP promotes MT transformation via mechanisms that depart from YAP's canonical oncogenic transcriptional activation functions. PMID- 27194758 TI - CD47 Plays a Role as a Negative Regulator in Inducing Protective Immune Responses to Vaccination against Influenza Virus. AB - An integrin-associated protein CD47, which is a ligand for the inhibitory receptor signal regulatory protein alpha, is expressed on B and T cells, as well as on most innate immune cells. However, the roles of CD47 in the immune responses to viral infection or vaccination remain unknown. We investigated the role of CD47 in inducing humoral immune responses after intranasal infection with virus or immunization with influenza virus-like particles (VLPs). Virus infection or vaccination with VLPs containing hemagglutinin from A/PR8/34 influenza virus induced higher levels of antigen-specific IgG2c isotype dominant antibodies in CD47-deficient (CD47KO) mice than in wild-type (WT) mice. CD47KO mice with vaccination showed greater protective efficacy against lethal challenge, as evidenced by no loss in body weight and reduced lung viral titers compared to WT mice. In addition, inflammatory responses which include cytokine production, leukocyte infiltrates, and gamma interferon-producing CD4(+) T cells, as well as an anti-inflammatory cytokine (interleukin-10), were reduced in the lungs of vaccinated CD47KO mice after challenge with influenza virus. Analysis of lymphocytes indicated that GL7(+) germinal center B cells were induced at higher levels in the draining lymph nodes of CD47KO mice compared to those in WT mice. Notably, CD47KO mice exhibited significant increases in the numbers of antigen specific memory B cells in spleens and plasma cells in bone marrow despite their lower levels of background IgG antibodies. These results suggest that CD47 plays a role as a negative regulator in inducing protective immune responses to influenza vaccination. IMPORTANCE: Molecular mechanisms that control B cell activation to produce protective antibodies upon viral vaccination remain poorly understood. The CD47 molecule is known to be a ligand for the inhibitory receptor signal regulatory protein alpha and expressed on the surfaces of most immune cell types. CD47 was previously demonstrated to play an important role in modulating the migration of monocytes, neutrophils, polymorphonuclear neutrophils, and dendritic cells into the inflamed tissues. The results of this study demonstrate new roles of CD47 in negatively regulating the induction of protective IgG antibodies, germinal center B cells, and plasma cells secreting antigen-specific antibodies, as well as macrophages, upon influenza vaccination and challenge. As a consequence, vaccinated CD47-deficient mice demonstrated better control of influenza viral infection and enhanced protection. This study provides insights into understanding the regulatory functions of CD47 in inducing adaptive immunity to vaccination. PMID- 27194759 TI - Mosaic H5 Hemagglutinin Provides Broad Humoral and Cellular Immune Responses against Influenza Viruses. AB - The most effective way to prevent influenza virus infection is via vaccination. However, the constant mutation of influenza viruses due to antigenic drift and shift compromises vaccine efficacy. This represents a major challenge to the development of a cross-protective vaccine that can protect against circulating viral antigenic diversity. Using the modified vaccinia Ankara (MVA) virus, we had previously generated a recombinant vaccine against highly pathogenic avian influenza virus (H5N1) based on an in silico mosaic approach. This MVA-H5M construct protected mice against multiple clades of H5N1 and H1N1 viruses. We have now further characterized the immune responses using immunodepletion of T cells and passive serum transfer, and these studies indicate that antibodies are the main contributors in homosubtypic protection (H5N1 clades). Compared to a MVA construct expressing hemagglutinin (HA) from influenza virus A/VN/1203/04 (MVA HA), the MVA-H5M vaccine markedly increased and broadened B cell and T cell responses against H5N1 virus. The MVA-H5M also provided effective protection with no morbidity against H5N1 challenge, whereas MVA-HA-vaccinated mice showed clinical signs and experienced significant weight loss. In addition, MVA-H5M induced CD8(+) T cell responses that play a major role in heterosubtypic protection (H1N1). Finally, expression of the H5M gene as either a DNA vaccine or a subunit protein protected mice against H5N1 challenge, indicating the effectiveness of the mosaic sequence without viral vectors for the development of a universal influenza vaccine. IMPORTANCE: Influenza viruses infect up to one billion people around the globe each year and are responsible for 300,000 to 500,000 deaths annually. Vaccines are still the main intervention to prevent infection, but they fail to provide effective protection against heterologous strains of viruses. We developed broadly reactive H5N1 vaccine based on an in silico mosaic approach and previously demonstrated that modified vaccinia Ankara expressing an H5 mosaic hemagglutinin prevented infection with multiple clades of H5N1 and limited severe disease after H1N1 infection. Further characterization revealed that antibody responses and T cells are main contributors to protection against H5N1 and H1N1 viruses, respectively. The vaccine also broadens both T cell and B cell responses compared to native H5 vaccine from influenza virus A/Vietnam/1203/04. Finally, delivering the H5 mosaic as a DNA vaccine or as a purified protein demonstrated effective protection similar to the viral vector approach. PMID- 27194760 TI - Uukuniemi Virus as a Tick-Borne Virus Model. AB - In the last decade, novel tick-borne pathogenic phleboviruses in the family Bunyaviridae, all closely related to Uukuniemi virus (UUKV), have emerged on different continents. To reproduce the tick-mammal switch in vitro, we first established a reverse genetics system to rescue UUKV with a genome close to that of the authentic virus isolated from the Ixodes ricinus tick reservoir. The IRE/CTVM19 and IRE/CTVM20 cell lines, both derived from I. ricinus, were susceptible to the virus rescued from plasmid DNAs and supported production of the virus over many weeks, indicating that infection was persistent. The glycoprotein GC was mainly highly mannosylated on tick cell-derived viral progeny. The second envelope viral protein, GN, carried mostly N-glycans not recognized by the classical glycosidases peptide-N-glycosidase F (PNGase F) and endoglycosidase H (Endo H). Treatment with beta-mercaptoethanol did not impact the apparent molecular weight of GN On viruses originating from mammalian BHK-21 cells, GN glycosylations were exclusively sensitive to PNGase F, and the electrophoretic mobility of the protein was substantially slower after the reduction of disulfide bonds. Furthermore, the amount of viral nucleoprotein per focus forming unit differed markedly whether viruses were produced in tick or BHK 21 cells, suggesting a higher infectivity for tick cell-derived viruses. Together, our results indicate that UUKV particles derived from vector tick cells have glycosylation and structural specificities that may influence the initial infection in mammalian hosts. This study also highlights the importance of working with viruses originating from arthropod vector cells in investigations of the cell biology of arbovirus transmission and entry into mammalian hosts. IMPORTANCE: Tick-borne phleboviruses represent a growing threat to humans globally. Although ticks are important vectors of infectious emerging diseases, previous studies have mainly involved virus stocks produced in mammalian cells. This limitation tends to minimize the importance of host alternation in virus transmission to humans and initial infection at the molecular level. With this study, we have developed an in vitro tick cell-based model that allows production of the tick-borne Uukuniemi virus to high titers. Using this system, we found that virions derived from tick cells have specific structural properties and N glycans that may enhance virus infectivity for mammalian cells. By shedding light on molecular aspects of tick-derived viral particles, our data illustrate the importance of considering the host switch in studying early virus-mammalian receptor/cell interactions. The information gained here lays the basis for future research on not only tick-borne phleboviruses but also all viruses and other pathogens transmitted by ticks. PMID- 27194761 TI - Cell-to-Cell Contact and Nectin-4 Govern Spread of Measles Virus from Primary Human Myeloid Cells to Primary Human Airway Epithelial Cells. AB - Measles is a highly contagious, acute viral illness. Immune cells within the airways are likely first targets of infection, and these cells traffic measles virus (MeV) to lymph nodes for amplification and subsequent systemic dissemination. Infected immune cells are thought to return MeV to the airways; however, the mechanisms responsible for virus transfer to pulmonary epithelial cells are poorly understood. To investigate this process, we collected blood from human donors and generated primary myeloid cells, specifically, monocyte-derived macrophages (MDMs) and dendritic cells (DCs). MDMs and DCs were infected with MeV and then applied to primary cultures of well-differentiated airway epithelial cells from human donors (HAE). Consistent with previous results obtained with free virus, infected MDMs or DCs were incapable of transferring MeV to HAE when applied to the apical surface. Likewise, infected MDMs or DCs applied to the basolateral surface of HAE grown on small-pore (0.4-MUm) support membranes did not transfer virus. In contrast, infected MDMs and DCs applied to the basolateral surface of HAE grown on large-pore (3.0-MUm) membranes successfully transferred MeV. Confocal microscopy demonstrated that MDMs and DCs are capable of penetrating large-pore membranes but not small-pore membranes. Further, by using a nectin-4 blocking antibody or recombinant MeV unable to enter cells through nectin-4, we demonstrated formally that transfer from immune cells to HAE occurs in a nectin-4-dependent manner. Thus, both infected MDMs and DCs rely on cell-to cell contacts and nectin-4 to efficiently deliver MeV to the basolateral surface of HAE. IMPORTANCE: Measles virus spreads rapidly and efficiently in human airway epithelial cells. This rapid spread is based on cell-to-cell contact rather than on particle release and reentry. Here we posit that MeV transfer from infected immune cells to epithelial cells also occurs by cell-to-cell contact rather than through cell-free particles. In addition, we sought to determine which immune cells transfer MeV infectivity to the human airway epithelium. Our studies are based on two types of human primary cells: (i) myeloid cells generated from donated blood and (ii) well-differentiated airway epithelial cells derived from donor lungs. We show that different types of myeloid cells, i.e., monocyte derived macrophages and dendritic cells, transfer infection to airway epithelial cells. Furthermore, cell-to-cell contact is an important component of successful MeV transfer. Our studies elucidate a mechanism by which the most contagious human respiratory virus is delivered to the airway epithelium. PMID- 27194762 TI - CD8+ T Cell Breadth and Ex Vivo Virus Inhibition Capacity Distinguish between Viremic Controllers with and without Protective HLA Class I Alleles. AB - The mechanisms of viral control and loss of viral control in chronically infected individuals with or without protective HLA class I alleles are not fully understood. We therefore characterized longitudinally the immunological and virological features that may explain divergence in disease outcome in 70 HIV-1 C clade-infected antiretroviral therapy (ART)-naive South African adults, 35 of whom possessed protective HLA class I alleles. We demonstrate that, over 5 years of longitudinal study, 35% of individuals with protective HLA class I alleles lost viral control compared to none of the individuals without protective HLA class I alleles (P = 0.06). Sustained HIV-1 control in patients with protective HLA class I alleles was characteristically related to the breadth of HIV-1 CD8(+) T cell responses against Gag and enhanced ability of CD8(+) T cells to suppress viral replication ex vivo In some cases, loss of virological control was associated with reduction in the total breadth of CD8(+) T cell responses in the absence of differences in HIV-1-specific CD8(+) T cell polyfunctionality or proliferation. In contrast, viremic controllers without protective HLA class I alleles possessed reduced breadth of HIV-1-specific CD8(+) T cell responses characterized by reduced ability to suppress viral replication ex vivo These data suggest that the control of HIV-1 in individuals with protective HLA class I alleles may be driven by broad CD8(+) T cell responses with potent viral inhibitory capacity while control among individuals without protective HLA class I alleles may be more durable and mediated by CD8(+) T cell-independent mechanisms. IMPORTANCE: Host mechanisms of natural HIV-1 control are not fully understood. In a longitudinal study of antiretroviral therapy (ART)-naive individuals, we show that those with protective HLA class I alleles subsequently experienced virologic failure compared to those without protective alleles. Among individuals with protective HLA class I alleles, viremic control was associated with broad CD8(+) T cells that targeted the Gag protein, and CD8(+) T cells from these individuals exhibited superior virus inhibition capacity. In individuals without protective HLA class I alleles, HIV-1-specific CD8(+) T cell responses were narrow and poorly inhibited virus replication. These results suggest that broad, highly functional cytotoxic T cells (cytotoxic T lymphocytes [CTLs]) against the HIV-1 Gag protein are associated with control among those with protective HLA class I alleles and that loss of these responses eventually leads to viremia. A subset of individuals appears to have alternative, non-CTL mechanisms of viral control. These controllers may hold the key to an effective HIV vaccine. PMID- 27194763 TI - Measurements of Intrahost Viral Diversity Are Extremely Sensitive to Systematic Errors in Variant Calling. AB - With next-generation sequencing technologies, it is now feasible to efficiently sequence patient-derived virus populations at a depth of coverage sufficient to detect rare variants. However, each sequencing platform has characteristic error profiles, and sample collection, target amplification, and library preparation are additional processes whereby errors are introduced and propagated. Many studies account for these errors by using ad hoc quality thresholds and/or previously published statistical algorithms. Despite common usage, the majority of these approaches have not been validated under conditions that characterize many studies of intrahost diversity. Here, we use defined populations of influenza virus to mimic the diversity and titer typically found in patient derived samples. We identified single-nucleotide variants using two commonly employed variant callers, DeepSNV and LoFreq. We found that the accuracy of these variant callers was lower than expected and exquisitely sensitive to the input titer. Small reductions in specificity had a significant impact on the number of minority variants identified and subsequent measures of diversity. We were able to increase the specificity of DeepSNV to >99.95% by applying an empirically validated set of quality thresholds. When applied to a set of influenza virus samples from a household-based cohort study, these changes resulted in a 10-fold reduction in measurements of viral diversity. We have made our sequence data and analysis code available so that others may improve on our work and use our data set to benchmark their own bioinformatics pipelines. Our work demonstrates that inadequate quality control and validation can lead to significant overestimation of intrahost diversity. IMPORTANCE: Advances in sequencing technology have made it feasible to sequence patient-derived viral samples at a level sufficient for detection of rare mutations. These high-throughput, cost-effective methods are revolutionizing the study of within-host viral diversity. However, the techniques are error prone, and the methods commonly used to control for these errors have not been validated under the conditions that characterize patient-derived samples. Here, we show that these conditions affect measurements of viral diversity. We found that the accuracy of previously benchmarked analysis pipelines was greatly reduced under patient-derived conditions. By carefully validating our sequencing analysis using known control samples, we were able to identify biases in our method and to improve our accuracy to acceptable levels. Application of our modified pipeline to a set of influenza virus samples from a cohort study provided a realistic picture of intrahost diversity and suggested the need for rigorous quality control in such studies. PMID- 27194764 TI - Identification of Diverse Mycoviruses through Metatranscriptomics Characterization of the Viromes of Five Major Fungal Plant Pathogens. AB - Mycoviruses can have a marked effect on natural fungal communities and influence plant health and productivity. However, a comprehensive picture of mycoviral diversity is still lacking. To characterize the viromes of five widely dispersed plant-pathogenic fungi, Colletotrichum truncatum, Macrophomina phaseolina, Diaporthe longicolla, Rhizoctonia solani, and Sclerotinia sclerotiorum, a high throughput sequencing-based metatranscriptomic approach was used to detect viral sequences. Total RNA and double-stranded RNA (dsRNA) from mycelia and RNA from samples enriched for virus particles were sequenced. Sequence data were assembled de novo, and contigs with predicted amino acid sequence similarities to viruses in the nonredundant protein database were selected. The analysis identified 72 partial or complete genome segments representing 66 previously undescribed mycoviruses. Using primers specific for each viral contig, at least one fungal isolate was identified that contained each virus. The novel mycoviruses showed affinity with 15 distinct lineages: Barnaviridae, Benyviridae, Chrysoviridae, Endornaviridae, Fusariviridae, Hypoviridae, Mononegavirales, Narnaviridae, Ophioviridae, Ourmiavirus, Partitiviridae, Tombusviridae, Totiviridae, Tymoviridae, and Virgaviridae More than half of the viral sequences were predicted to be members of the Mitovirus genus in the family Narnaviridae, which replicate within mitochondria. Five viral sequences showed strong affinity with three families (Benyviridae, Ophioviridae, and Virgaviridae) that previously contained no mycovirus species. The genomic information provides insight into the diversity and taxonomy of mycoviruses and coevolution of mycoviruses and their fungal hosts. IMPORTANCE: Plant-pathogenic fungi reduce crop yields, which affects food security worldwide. Plant host resistance is considered a sustainable disease management option but may often be incomplete or lacking for some crops to certain fungal pathogens or strains. In addition, the rising issues of fungicide resistance demand alternative strategies to reduce the negative impacts of fungal pathogens. Those fungus-infecting viruses (mycoviruses) that attenuate fungal virulence may be welcome additions for mitigation of plant diseases. By high-throughput sequencing of the RNAs from 275 isolates of five fungal plant pathogens, 66 previously undescribed mycoviruses were identified. In addition to identifying new potential biological control agents, these results expand the grand view of the diversity of mycoviruses and provide possible insights into the importance of intracellular and extracellular transmission in fungus-virus coevolution. PMID- 27194765 TI - Dynein Regulators Are Important for Ecotropic Murine Leukemia Virus Infection. AB - During the early steps of infection, retroviruses must direct the movement of the viral genome into the nucleus to complete their replication cycle. This process is mediated by cellular proteins that interact first with the reverse transcription complex and later with the preintegration complex (PIC), allowing it to reach and enter the nucleus. For simple retroviruses, such as murine leukemia virus (MLV), the identities of the cellular proteins involved in trafficking of the PIC in infection are unknown. To identify cellular proteins that interact with the MLV PIC, we developed a replication-competent MLV in which the integrase protein was tagged with a FLAG epitope. Using a combination of immunoprecipitation and mass spectrometry, we established that the microtubule motor dynein regulator DCTN2/p50/dynamitin interacts with the MLV preintegration complex early in infection, suggesting a direct interaction between the incoming viral particles and the dynein complex regulators. Further experiments showed that RNA interference (RNAi)-mediated silencing of either DCTN2/p50/dynamitin or another dynein regulator, NudEL, profoundly reduced the efficiency of infection by ecotropic, but not amphotropic, MLV reporters. We propose that the cytoplasmic dynein regulators are a critical component of the host machinery needed for infection by the retroviruses entering the cell via the ecotropic envelope pathway. IMPORTANCE: Retroviruses must access the chromatin of host cells to integrate the viral DNA, but before this crucial event, they must reach the nucleus. The movement through the cytoplasm-a crowded environment where diffusion is slow-is thought to utilize retrograde transport along the microtubule network by the dynein complex. Different viruses use different components of this multisubunit complex. We found that the preintegration complex of murine leukemia virus (MLV) interacts with the dynein complex and that regulators of this complex are essential for infection. Our study provides the first insight into the requirements for retrograde transport of the MLV preintegration complex. PMID- 27194766 TI - ISG12a Restricts Hepatitis C Virus Infection through the Ubiquitination-Dependent Degradation Pathway. AB - Interferons (IFNs) restrict various kinds of viral infection via induction of hundreds of IFN-stimulated genes (ISGs), while the functions of the majority of ISGs are broadly unclear. Here, we show that a high-IFN-inducible gene, ISG12a (also known as IFI27), exhibits a nonapoptotic antiviral effect on hepatitis C virus (HCV) infection. Viral NS5A protein is targeted specifically by ISG12a, which mediates NS5A degradation via a ubiquitination-dependent proteasomal pathway. K374R mutation in NS5A domain III abrogates ISG12a-induced ubiquitination and degradation of NS5A. S-phase kinase-associated protein 2 (SKP2) is identified as an ubiquitin E3 ligase for NS5A. ISG12a functions as a crucial adaptor that promotes SKP2 to interact with and degrade viral protein. Moreover, the antiviral effect of ISG12a is dependent on the E3 ligase activity of SKP2. These findings uncover an intriguing mechanism by which ISG12a restricts viral infection and provide clues for understanding the actions of innate immunity. IMPORTANCE: Upon virus invasion, IFNs induce numerous ISGs to control viral spread, while the functions of the majority of ISGs are broadly unclear. The present study shows a novel antiviral mechanism of ISGs and elucidated that ISG12a recruits an E3 ligase, SKP2, for ubiquitination and degradation of viral protein and restricts viral infection. These findings provide important insights into exploring the working principles of innate immunity. PMID- 27194767 TI - Small-Molecule Fusion Inhibitors Bind the pH-Sensing Stable Signal Peptide-GP2 Subunit Interface of the Lassa Virus Envelope Glycoprotein. AB - Arenavirus species are responsible for severe life-threatening hemorrhagic fevers in western Africa and South America. Without effective antiviral therapies or vaccines, these viruses pose serious public health and biodefense concerns. Chemically distinct small-molecule inhibitors of arenavirus entry have recently been identified and shown to act on the arenavirus envelope glycoprotein (GPC) to prevent membrane fusion. In the tripartite GPC complex, pH-dependent membrane fusion is triggered through a poorly understood interaction between the stable signal peptide (SSP) and the transmembrane fusion subunit GP2, and our genetic studies have suggested that these small-molecule inhibitors act at this interface to antagonize fusion activation. Here, we have designed and synthesized photoaffinity derivatives of the 4-acyl-1,6-dialkylpiperazin-2-one class of fusion inhibitors and demonstrate specific labeling of both the SSP and GP2 subunits in a native-like Lassa virus (LASV) GPC trimer expressed in insect cells. Photoaddition is competed by the parental inhibitor and other chemically distinct compounds active against LASV, but not those specific to New World arenaviruses. These studies provide direct physical evidence that these inhibitors bind at the SSP-GP2 interface. We also find that GPC containing the uncleaved GP1-GP2 precursor is not susceptible to photo-cross-linking, suggesting that proteolytic maturation is accompanied by conformational changes at this site. Detailed mapping of residues modified by the photoaffinity adducts may provide insight to guide the further development of these promising lead compounds as potential therapeutic agents to treat Lassa hemorrhagic fever. IMPORTANCE: Hemorrhagic fever arenaviruses cause lethal infections in humans and, in the absence of licensed vaccines or specific antiviral therapies, are recognized to pose significant threats to public health and biodefense. Lead small-molecule inhibitors that target the arenavirus envelope glycoprotein (GPC) have recently been identified and shown to block GPC-mediated fusion of the viral and cellular endosomal membranes, thereby preventing virus entry into the host cell. Genetic studies suggest that these inhibitors act through a unique pH sensing intersubunit interface in GPC, but atomic-level structural information is unavailable. In this report, we utilize novel photoreactive fusion inhibitors and photoaffinity labeling to obtain direct physical evidence for inhibitor binding at this critical interface in Lassa virus GPC. Future identification of modified residues at the inhibitor-binding site will help elucidate the molecular basis for fusion activation and its inhibition and guide the development of effective therapies to treat arenaviral hemorrhagic fevers. PMID- 27194772 TI - Answers to Illuminations questions. PMID- 27194769 TI - Stability of HIV Frameshift Site RNA Correlates with Frameshift Efficiency and Decreased Virus Infectivity. AB - Human immunodeficiency virus (HIV) replication is strongly dependent upon a programmed ribosomal frameshift. Here we investigate the relationships between the thermodynamic stability of the HIV type 1 (HIV-1) RNA frameshift site stem loop, frameshift efficiency, and infectivity, using pseudotyped HIV-1 and HEK293T cells. The data reveal a strong correlation between frameshift efficiency and local, but not overall, RNA thermodynamic stability. Mutations that modestly increase the local stability of the frameshift site RNA stem-loop structure increase frameshift efficiency 2-fold to 3-fold in cells. Thus, frameshift efficiency is determined by the strength of the thermodynamic barrier encountered by the ribosome. These data agree with previous in vitro measurements, suggesting that there are no virus- or host-specific factors that modulate frameshifting. The data also indicate that there are no sequence-specific requirements for the frameshift site stem-loop. A linear correlation between Gag-polymerase (Gag-Pol) levels in cells and levels in virions supports the idea of a stochastic virion assembly mechanism. We further demonstrate that the surrounding genomic RNA secondary structure influences frameshift efficiency and that a mutation that commonly arises in response to protease inhibitor therapy creates a functional but inefficient secondary slippery site. Finally, HIV-1 mutants with enhanced frameshift efficiencies are significantly less infectious, suggesting that compounds that increase frameshift efficiency by as little as 2-fold may be effective at suppressing HIV-1 replication. IMPORTANCE: HIV, like many retroviruses, utilizes a -1 programmed ribosomal frameshift to generate viral enzymes in the form of a Gag-Pol polyprotein precursor. Thus, frameshifting is essential for viral replication. Here, we utilized a panel of mutant HIV strains to demonstrate that in cells, frameshifting efficiency is correlated with the stability of the local thermodynamic barrier to ribosomal translocation. Increasing the stability of the frameshift site RNA increases the frameshift efficiency 2-fold to 3-fold. Mutant viruses with increased frameshift efficiencies have significantly reduced infectivity. These data suggest that this effect might be exploited in the development of novel antiviral strategies. PMID- 27194770 TI - Functional Incompatibility between the Generic NF-kappaB Motif and a Subtype Specific Sp1III Element Drives the Formation of the HIV-1 Subtype C Viral Promoter. AB - Of the various genetic subtypes of human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) and simian immunodeficiency virus (SIV), only in subtype C of HIV-1 is a genetically variant NF-kappaB binding site found at the core of the viral promoter in association with a subtype-specific Sp1III motif. How the subtype-associated variations in the core transcription factor binding sites (TFBS) influence gene expression from the viral promoter has not been examined previously. Using panels of infectious viral molecular clones, we demonstrate that subtype-specific NF-kappaB and Sp1III motifs have evolved for optimal gene expression, and neither of the motifs can be replaced by a corresponding TFBS variant. The variant NF-kappaB motif binds NF-kappaB with an affinity 2-fold higher than that of the generic NF-kappaB site. Importantly, in the context of an infectious virus, the subtype-specific Sp1III motif demonstrates a profound loss of function in association with the generic NF-kappaB motif. An additional substitution of the Sp1III motif fully restores viral replication, suggesting that the subtype C-specific Sp1III has evolved to function with the variant, but not generic, NF-kappaB motif. A change of only two base pairs in the central NF kappaB motif completely suppresses viral transcription from the provirus and converts the promoter into heterochromatin refractory to tumor necrosis factor alpha (TNF-alpha) induction. The present work represents the first demonstration of functional incompatibility between an otherwise functional NF-kappaB motif and a unique Sp1 site in the context of an HIV-1 promoter. Our work provides important leads as to the evolution of the HIV-1 subtype C viral promoter with relevance for gene expression regulation and viral latency. IMPORTANCE: Subtype specific genetic variations provide a powerful tool to examine how these variations offer a replication advantage to specific viral subtypes, if any. Only in subtype C of HIV-1 are two genetically distinct transcription factor binding sites positioned at the most critical location of the viral promoter. Since a single promoter regulates viral gene expression, the promoter variations can play a critical role in determining the replication fitness of the viral strains. Our work for the first time provides a scientific explanation for the presence of a unique NF-kappaB binding motif in subtype C, a major HIV-1 genetic family responsible for half of the global HIV-1 infections. The results offer compelling evidence that the subtype C viral promoter not only is stronger but also is endowed with a qualitative gain-of-function advantage. The genetically variant NF kappaB and the Sp1III motifs may be respond differently to specific cell signal pathways, and these mechanisms must be examined. PMID- 27194773 TI - Answers to Epilogue questions. PMID- 27194768 TI - Both cis and trans Activities of Foot-and-Mouth Disease Virus 3D Polymerase Are Essential for Viral RNA Replication. AB - The Picornaviridae is a large family of positive-sense RNA viruses that contains numerous human and animal pathogens, including foot-and-mouth disease virus (FMDV). The picornavirus replication complex comprises a coordinated network of protein-protein and protein-RNA interactions involving multiple viral and host cellular factors. Many of the proteins within the complex possess multiple roles in viral RNA replication, some of which can be provided in trans (i.e., via expression from a separate RNA molecule), while others are required in cis (i.e., expressed from the template RNA molecule). In vitro studies have suggested that multiple copies of the RNA-dependent RNA polymerase (RdRp) 3D are involved in the viral replication complex. However, it is not clear whether all these molecules are catalytically active or what other function(s) they provide. In this study, we aimed to distinguish between catalytically active 3D molecules and those that build a replication complex. We report a novel nonenzymatic cis-acting function of 3D that is essential for viral-genome replication. Using an FMDV replicon in complementation experiments, our data demonstrate that this cis-acting role of 3D is distinct from the catalytic activity, which is predominantly trans acting. Immunofluorescence studies suggest that both cis- and trans-acting 3D molecules localize to the same cellular compartment. However, our genetic and structural data suggest that 3D interacts in cis with RNA stem-loops that are essential for viral RNA replication. This study identifies a previously undescribed aspect of picornavirus replication complex structure-function and an important methodology for probing such interactions further. IMPORTANCE: Foot-and-mouth disease virus (FMDV) is an important animal pathogen responsible for foot-and-mouth disease. The disease is endemic in many parts of the world with outbreaks within livestock resulting in major economic losses. Propagation of the viral genome occurs within replication complexes, and understanding this process can facilitate the development of novel therapeutic strategies. Many of the nonstructural proteins involved in replication possess multiple functions in the viral life cycle, some of which can be supplied to the replication complex from a separate genome (i.e., in trans) while others must originate from the template (i.e., in cis). Here, we present an analysis of cis and trans activities of the RNA-dependent RNA polymerase 3D. We demonstrate a novel cis-acting role of 3D in replication. Our data suggest that this role is distinct from its enzymatic functions and requires interaction with the viral genome. Our data further the understanding of genome replication of this important pathogen. PMID- 27194774 TI - Answers to Epilogue questions. PMID- 27194775 TI - Answers to Epilogue questions. PMID- 27194776 TI - Answers to Epilogue questions. PMID- 27194777 TI - Fever, confusion, acute kidney injury: is this atypical neuroleptic malignant syndrome following polypharmacy with clozapine and risperidone? AB - OBJECTIVE: Clozapine is the gold-standard antipsychotic medication for treatment refractory schizophrenia (TRS). However, one potentially lethal side effect of clozapine, as with other antipsychotics, is neuroleptic malignant syndrome (NMS) which could present differently in clozapine therapy. 'Atypical NMS' is a recognised variant of NMS with less rigidity and delayed elevation of creatine kinase; this variant is associated with clozapine. METHOD: A case from the author's clinical practice was reviewed. RESULTS: A 67-year-old man with TRS was treated with clozapine. Unfortunately, his physical condition deteriorated and he presented with atypical NMS, which initially was treated as presumable urinary tract infection. CONCLUSIONS: Atypical NMS is associated with clozapine. This case exposes the potential difficulties in diagnosis, and highlights the importance of considering less common diagnoses in acutely unwell psychiatric patients. PMID- 27194778 TI - Plumbing, philosophy and psychiatry. AB - OBJECTIVES: To briefly examine shortcomings in the foundation concepts that underlie theory and thought in contemporary psychiatry and to argue that these shortcomings mislead research and practice. CONCLUSIONS: Psychiatry stands on a complex of ideas and concepts that cannot be reduced to a satisfying or unifying underlying conceptual system or idea. The ideas and concepts have been patched together ad hoc and function until things go wrong. Growing professional dispute and public disquiet indicates that things are going wrong. I suggest that professional philosophers need to be engaged in the necessary infrastructure repairs. PMID- 27194779 TI - Finding an effective treatment for microvascular obstruction in STEMI: a road to perdition? PMID- 27194780 TI - Influence of Biochemical and Anthropometric Factors on the Presence of Insulin Resistance in Adolescents. AB - BACKGROUND: Insulin resistance plays a determinant role in the development of metabolic syndrome in adolescents. The objective of the present study was to determine the influence of factors commonly associated with insulin resistance in a sample of adolescents. METHODS: This cross-sectional study included 976 adolescents from southeast Spain. Anthropometric and biochemical measurements were performed, and insulin resistance was assessed using the homeostasis model assessment-insulin resistance (HOMA-IR). RESULTS: Subjects with abnormal HOMA-IR values had significantly higher body mass index (BMI), body fat content, waist circumference, and systolic blood pressure (BP) than those with normal values. Furthermore, levels of glucose, insulin, glycosylated hemoglobin, total cholesterol, triglycerides, low-density lipoprotein-cholesterol, homocysteine, nonesterified fatty acids, and ceruloplasmin were higher in subjects with abnormal HOMA-IR values. Multivariate logistic regression analysis showed the highest odds ratio (OR) for BMI and that combinations of BMI with body fat content or systolic BP can increase the risk of insulin resistance 7-fold. DISCUSSION: Anthropometric indicators have different levels of influence on the risk of insulin resistance in adolescents, and a combination of two of these indicators is enough to increase the risk 7-fold. Since the highest OR was observed for BMI, the greatest effort should be directed to reducing this parameter in adolescents. An adequate understanding by nursing personnel of factors associated with insulin resistance is a key factor in the prevention of this pathophysiological condition and its complications in adolescents. PMID- 27194781 TI - Mitral regurgitation in heart failure: insights from CPET combined with exercise echocardiography. AB - Aims: In heart failure patients with reduced ejection fraction (HFrEF), exercise induced functional mitral regurgitation (MR) may affect functional capacity and outcome. We sought to study functional and cardiac phenotypes of HFrEF patients according to the MR degree. Methods and results: We performed rest and exercise echocardiography (Ex-Echo), simultaneously combined with cardiopulmonary exercise test (CPET), in 102 HFrEF patients, identifying 3 groups: non-severe (ERO <20 mm2) MR (group A), exercise-induced severe (ERO >=20 mm2) MR (group B), and rest severe MR (group C). Patients were tracked for the composite end point of death and heart failure hospitalization. Group B (ERO: rest= 14 +/- 5 mm2, Ex= 28 +/- 6 mm2; P = < 0.001) had a functional impairment (workload = 56 +/- 21 vs. 50 +/- 17 watts, P = 0.42; peak VO2 = 11.8 +/- 3.2 vs. 11.5 +/- 3.0 mL/Kg/min, P = 0.70) similar to Group C (ERO: rest = 29 +/- 7 mm2, Ex = 42 +/- 7 mm2, P = < 0.001), associated with comparable advanced left ventricle remodelling (end diastolic indexed volume = 107 +/- 34 vs. 115 +/- 30 mL/m2, P = 0.27), characterized by exercise-induced pulmonary hypertension (PH) (Ex systolic pulmonary pressures = 63 +/- 16 mmHg). Group C showed the worse cardiac phenotype (right ventricle dilatation, dysfunction, and rest PH) with severe ventilatory impairment (VE/VCO2 = 41.2 +/- 11) compared with Groups A and B. Moreover, Group C had the higher rate of death and HF hospitalization. Conclusions: In HFrEF patients, severe dynamic MR produces functional limitation similar to rest severe MR, characterized by dynamic PH. Rest severe MR reflects the most advanced bi ventricular remodelling associated with rest PH, the most unfavourable ventilatory profile, and the worst mid-term outcome. PMID- 27194782 TI - Prognostic value of left atrial function in systemic light-chain amyloidosis: a cardiac magnetic resonance study. AB - BACKGROUND: Cardiac involvement in systemic light-chain amyloidosis (AL) imparts an adverse impact on outcome. The left atrium (LA), by virtue of its anatomical location and muscular wall, is commonly affected by the amyloid process. Although LA infiltration by amyloid fibrils leads to a reduction in its pump function, the infiltration of the left ventricular (LV) myocardium results in diastolic dysfunction with subsequent increase in filling pressures and LA enlargement. Even though left atrial volume (LAV) is an independent prognostic marker in many cardiomyopathies, its value in amyloid heart disease remains to be determined. In addition, few data are available as to the prognostic value of LA function in systemic AL. Using cardiac magnetic resonance (CMR), the current study aims to assess the prognostic significance of the maximal LAV and total LA emptying fraction (LAEF) in patients with AL. METHODS AND RESULTS: Fifty-four consecutive patients (age 66 +/- 10 years, 59% males) with confirmed systemic AL and mean LV ejection fraction of 60 +/- 12% underwent CMR. As compared with patients with no or minimal cardiac involvement (Mayo Clinic [MC] stage I), those at moderate and high risk (MC stages II and III) had significantly larger indexed maximal LAV (36 +/- 15 vs. 46 +/- 13 vs. 52 +/- 19 mL/m(2), P = 0.03) and indexed minimal LAV (20 +/- 6 vs. 34 +/- 11 vs. 44 +/- 17 mL/m(2), P < 0.001), lower LAEF (42 +/- 9 vs. 26 +/- 13 vs. 16 +/- 9%, P < 0.0001) but similar LVEF. Furthermore, myocardial late gadolinium enhancement (LGE) was more frequent and significantly associated with lower LAEF. LAEF was also significantly lower in symptomatic (NHYA >= II, 22 +/- 14%) as compared with asymptomatic patients (NYHA class I, 33 +/- 13%, P = 0.006). Two-year survival rate was lower in patients with LAEF <= 16% as compared with those with LAEF > 16% (37 +/- 11 vs. 94 +/- 4%, P = 0.001). In multivariate analysis, lower LAEF remained independently associated with a higher risk of 2 year mortality (HR = 1.08 per 1% decrease, 95% CI: 1.02-1.15, P = 0.003). CONCLUSION: In patients with systemic AL, LAEF as assessed by CMR is associated with NYHA functional class, MC stage, myocardial LGE and 2-year mortality. PMID- 27194783 TI - Phosphoinositide 3-Kinase delta Regulates Dectin-2 Signaling and the Generation of Th2 and Th17 Immunity. AB - The C-type lectin receptor Dectin-2 can trigger the leukotriene C4 synthase dependent generation of cysteinyl leukotrienes and the caspase-associated recruitment domain 9- and NF-kappaB-dependent generation of cytokines, such as IL 23, IL-6, and TNF-alpha, to promote Th2 and Th17 immunity, respectively. Dectin-2 activation also elicits the type 2 cytokine IL-33, but the mechanism by which Dectin-2 induces these diverse innate mediators is poorly understood. In this study, we identify a common upstream requirement for PI3Kdelta activity for the generation of each Dectin-2-dependent mediator elicited by the house dust mite species, Dermatophagoides farinae, using both pharmacologic inhibition and small interfering RNA knockdown of PI3Kdelta in bone marrow-derived dendritic cells. PI3Kdelta activity depends on spleen tyrosine kinase (Syk) and regulates the activity of protein kinase Cdelta, indicating that PI3Kdelta is a proximal Syk dependent signaling intermediate. Inhibition of PI3Kdelta also reduces cysteinyl leukotrienes and cytokines elicited by Dectin-2 cross-linking, confirming the importance of this molecule in Dectin-2 signaling. Using an adoptive transfer model, we demonstrate that inhibition of PI3Kdelta profoundly reduces the capacity of bone marrow-derived dendritic cells to sensitize recipient mice for Th2 and Th17 pulmonary inflammation in response to D. farinae Furthermore, administration of a PI3Kdelta inhibitor during the sensitization of wild-type mice prevents the generation of D. farinae-induced pulmonary inflammation. These results demonstrate that PI3Kdelta regulates Dectin-2 signaling and its dendritic cell function. PMID- 27194785 TI - HNRNPR Regulates the Expression of Classical and Nonclassical MHC Class I Proteins. AB - MHC class I molecules, in addition to their role in specific activation of the CTL of adaptive immune system, function also as the main ligands for NK cell inhibitory receptors, which prevent NK cells from killing normal, healthy cells. MHC class I proteins are divided into classical and nonclassical proteins. The former group consists of hundreds of HLA-A, B, and C alleles, which are universally expressed, whereas several alleles of the latter group, such as HLA G, manifest a restricted expression pattern. Despite the important role played by these molecules in innate and adaptive immune responses, their complex expression regulation is not fully known. In our study, we investigated the regulation processes controlling the expression of MHC class I molecules, with a particular focus on their 3' untranslated regions. We identified heterogeneous nuclear ribonucleoprotein R (HNRNPR) as an important positive regulator of classical and nonclassical MHC class I molecules. HNRNPR is a RNA-binding protein belonging to the heterogeneous nuclear ribonucleoprotein family, which has a known role in processing of precursor mRNA. We demonstrated that HNRNPR binds MHC class I mRNAs in their 3' untranslated regions and enhances their stability and consequently their expression. Furthermore, regulation by HNRNPR modulates the cytotoxic activity of NK cells. In conclusion, we show that HNRNPR acts as a general positive regulator of MHC class I expression. PMID- 27194784 TI - Correction of MFG-E8 Resolves Inflammation and Promotes Cutaneous Wound Healing in Diabetes. AB - Milk fat globule epidermal growth factor-factor 8 (MFG-E8) is a peripheral glycoprotein that acts as a bridging molecule between the macrophage and apoptotic cells, thus executing a pivotal role in the scavenging of apoptotic cells from affected tissue. We have previously reported that apoptotic cell clearance activity or efferocytosis is compromised in diabetic wound macrophages. In this work, we test the hypothesis that MFG-E8 helps resolve inflammation, supports angiogenesis, and accelerates wound closure. MFG-E8(-/-) mice displayed impaired efferocytosis associated with exaggerated inflammatory response, poor angiogenesis, and wound closure. Wound macrophage-derived MFG-E8 was recognized as a critical driver of wound angiogenesis. Transplantation of MFG-E8(-/-) bone marrow to MFG-E8(+/+) mice resulted in impaired wound closure and compromised wound vascularization. In contrast, MFG-E8(-/-) mice that received wild-type bone marrow showed improved wound closure and improved wound vascularization. Hyperglycemia and exposure to advanced glycated end products inactivated MFG-E8, recognizing a key mechanism that complicates diabetic wound healing. Diabetic db/db mice suffered from impaired efferocytosis accompanied with persistent inflammation and slow wound closure. Topical recombinant MFG-E8 induced resolution of wound inflammation, improvements in angiogenesis, and acceleration of closure, upholding the potential of MFG-E8-directed therapeutics in diabetic wound care. PMID- 27194786 TI - Lung Injury Combined with Loss of Regulatory T Cells Leads to De Novo Lung Restricted Autoimmunity. AB - More than one third of patients with chronic lung disease undergoing lung transplantation have pre-existing Abs against lung-restricted self-Ags, collagen type V (ColV), and k-alpha1 tubulin (KAT). These Abs can also develop de novo after lung transplantation and mediate allograft rejection. However, the mechanisms leading to lung-restricted autoimmunity remain unknown. Because these self-Ags are normally sequestered, tissue injury is required to expose them to the immune system. We previously showed that respiratory viruses can induce apoptosis in CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs), the key mediators of self-tolerance. Therefore, we hypothesized that lung-tissue injury can lead to lung-restricted immunity if it occurs in a setting when Tregs are impaired. We found that human lung recipients who suffer respiratory viral infections experienced a decrease in peripheral Tregs. Pre-existing lung allograft injury from donor-directed Abs or gastroesophageal reflux led to new ColV and KAT Abs post respiratory viral infection. Similarly, murine parainfluenza (Sendai) respiratory viral infection caused a decrease in Tregs. Intratracheal instillation of anti-MHC class I Abs, but not isotype control, followed by murine Sendai virus infection led to development of Abs against ColV and KAT, but not collagen type II (ColII), a cartilaginous protein. This was associated with expansion of IFN-gamma-producing CD4(+) T cells specific to ColV and KAT, but not ColII. Intratracheal anti-MHC class I Abs or hydrochloric acid in Foxp3-DTR mice induced ColV and KAT, but not ColII, immunity, only if Tregs were depleted using diphtheria toxin. We conclude that tissue injury combined with loss of Tregs can lead to lung-tissue-restricted immunity. PMID- 27194787 TI - Regulatory T Cell Dysfunction Acquiesces to BTLA+ Regulatory B Cells Subsequent to Oral Intervention in Experimental Autoimmune Encephalomyelitis. AB - Regulatory T cells (Tregs) induced during autoimmunity often become quiescent and unable to resolve disease, suggesting inadequate activation. Resolution of established experimental autoimmune encephalomyelitis (EAE) can be achieved with myelin oligodendrocyte glycoprotein (MOG) fused to reovirus protein sigma1 (MOG psigma1), which activates Tregs, restoring protection, but requiring other regulatory cells to revitalize them. B cells have a dichotomous role in both the pathogenesis and recovery from EAE. Although inflammatory B cells contribute to EAE's pathogenesis, treatment of EAE mice with MOG-psigma1, but not OVA-psigma1, resulted in an influx of IL-10-producing B220(+)CD5(+) B regulatory cells (Bregs) enabling Tregs to recover their inhibitory activity, and in turn, leading to the rapid amelioration of EAE. These findings implicate direct interactions between Bregs and Tregs to facilitate this recovery. Adoptive transfer of B220(+)CD5(-) B cells from MOG-psigma1-treated EAE or Bregs from PBS-treated EAE mice did not resolve disease, whereas the adoptive transfer of MOG-psigma1-induced B220(+)CD5(+) Bregs greatly ameliorated EAE. MOG-psigma1-, but not OVA-psigma1 induced IL-10-producing Bregs, expressed elevated levels of B and T lymphocyte attenuator (BTLA) relative to CD5(-) B cells, as opposed to Tregs or effector T (Teff) cells, whose BTLA expression was not affected. These induced Bregs restored EAE Treg function in a BTLA-dependent manner. BTLA(-/-) mice showed more pronounced EAE with fewer Tregs, but upon adoptive transfer of MOG-psigma1 induced BTLA(+) Bregs, BTLA(-/-) mice were protected against EAE. Hence, this evidence shows the importance of BTLA in activating Tregs to facilitate recovery from EAE. PMID- 27194789 TI - MSX1 Modulates RLR-Mediated Innate Antiviral Signaling by Facilitating Assembly of TBK1-Associated Complexes. AB - Recognition of viral dsRNA by the retinoic acid-inducible gene-1-like receptors (RLRs) triggers signaling cascades that lead to activation of the TBK1 kinase and transcription factor IFN regulatory factor 3, induction of downstream antiviral genes, and innate antiviral responses. In this study, we identified muscle segment homeobox1 (MSX1) as an important modulator of RLR-mediated signaling pathways. Knockdown or knockout of MSX1 significantly impaired Sendai virus triggered activation of TBK1 and IFN regulatory factor 3, induction of downstream antiviral genes, and cellular antiviral responses. Interestingly, MSX1 was translocated from the nucleus to cytoplasm, particularly mitochondria upon infection of Sendai virus. Biochemcially, MSX1 was important for assembly of TBK1/IKK-related kinase-associated protein 1/TNFR-associated factor-associated NF kappaB activator complexes. Our results suggest that MSX1 is an important component of RLR-mediated signaling and reveal mechanisms on innate immune responses against RNA viruses. PMID- 27194788 TI - Experimental Anti-Inflammatory Drug Semapimod Inhibits TLR Signaling by Targeting the TLR Chaperone gp96. AB - Semapimod, a tetravalent guanylhydrazone, suppresses inflammatory cytokine production and has potential in a variety of inflammatory and autoimmune disorders. The mechanism of action of Semapimod is not well understood. In this study, we demonstrate that in rat IEC-6 intestinal epithelioid cells, Semapimod inhibits activation of p38 MAPK and NF-kappaB and induction of cyclooxygenase-2 by TLR ligands, but not by IL-1beta or stresses. Semapimod inhibits TLR4 signaling (IC50 ~0.3 MUmol) and acts by desensitizing cells to LPS; it fails to block responses to LPS concentrations of >=5 MUg/ml. Inhibition of TLR signaling by Semapimod is almost instantaneous: the drug is effective when applied simultaneously with LPS. Semapimod blocks cell-surface recruitment of the MyD88 adapter, one of the earliest events in TLR signaling. gp96, the endoplasmic reticulum-localized chaperone of the HSP90 family critically involved in the biogenesis of TLRs, was identified as a target of Semapimod using ATP desthiobiotin pulldown and mass spectroscopy. Semapimod inhibits ATP-binding and ATPase activities of gp96 in vitro (IC50 ~0.2-0.4 MUmol). On prolonged exposure, Semapimod causes accumulation of TLR4 and TLR9 in perinuclear space, consistent with endoplasmic reticulum retention, an anticipated consequence of impaired gp96 chaperone function. Our data indicate that Semapimod desensitizes TLR signaling via its effect on the TLR chaperone gp96. Fast inhibition by Semapimod is consistent with gp96 participating in high-affinity sensing of TLR ligands in addition to its role as a TLR chaperone. PMID- 27194791 TI - Structural Basis for Eculizumab-Mediated Inhibition of the Complement Terminal Pathway. AB - Eculizumab is a humanized mAb approved for treatment of patients with paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. Eculizumab binds complement component C5 and prevents its cleavage by C5 convertases, inhibiting release of both the proinflammatory metabolite C5a and formation of the membrane attack complex via C5b. In this study, we present the crystal structure of the complex between C5 and a Fab fragment with the same sequence as eculizumab at a resolution of 4.2 A. Five CDRs contact the C5 macroglobulin 7 domain, which contains the entire epitope. A complete mutational scan of the 66 CDR residues identified 28 residues as important for the C5-eculizumab interaction, and the structure of the complex offered an explanation for the reduced C5 binding observed for these mutant Abs. Furthermore, the structural observations of the interaction are supported by the reduced ability of a subset of these mutated Abs to inhibit membrane attack complex formation as tested in a hemolysis assay. Our results suggest that eculizumab functions by sterically preventing C5 from binding to convertases and explain the exquisite selectivity of eculizumab for human C5 and how polymorphisms in C5 cause eculizumab-resistance in a small number of patients with paroxysmal nocturnal hemoglobinuria. PMID- 27194790 TI - Direct TLR-2 Costimulation Unmasks the Proinflammatory Potential of Neonatal CD4+ T Cells. AB - Neonatal CD4(+) T cells have traditionally been viewed as deficient in their capacity to produce Th1 cytokines in response to polyclonal or Ag-specific stimuli. Thus, defining unique aspects of CD4(+) T cell activation and development into Th1 effector cells in neonates is essential to the successful development of novel vaccines and immunotherapies to protect infants from intracellular pathogens. Using highly purified naive CD4(+) T cells derived from cord and adult peripheral blood, we compared the impact of anti-CD3 stimulation plus costimulation through TLR-2 performed in the absence of APC on CD4(+) T cell cytokine production, proliferation, and expression of activation markers. In both age groups, TLR-2 costimulation elicited activation of naive CD4(+) T cells, characterized by robust production of IL-2 as well as key Th1-type cytokines IFN gamma and TNF-alpha. TLR-2 costimulation also dramatically reduced naive T cell production of the immunosuppressive cytokine IL-10. We observed that neonatal naive CD4(+) T cells are uniquely sensitive to TLR-2-mediated costimulation, which enabled them to produce equivalent amounts of IFN-gamma and more IL-2 when compared with adult responses. Thus, neonatal CD4(+) T cells have a distinctive propensity to use TLR-2-mediated costimulation for development into proinflammatory Th1 effectors, and interventions that target CD4(+) T cell TLR-2 mediated responses may be exploited to enhance neonatal adaptive immunity. PMID- 27194792 TI - Illuminating odors: when optogenetics brings to light unexpected olfactory abilities. AB - For hundreds of years, the sense of smell has generated great interest in the world literature, oenologists, and perfume makers but less of scientists. Only recently this sensory modality has gained new attraction in neuroscience when original tools issued from physiology, anatomy, or molecular biology were available to decipher how the brain makes sense of olfactory cues. However, this move was promptly dampened by the difficulties of developing quantitative approaches to study the relationship between the physical characteristics of stimuli and the sensations they create. An upswing of olfactory investigations occurred when genetic tools could be used in combination with devices borrowed from the physics of light (a hybrid technique called optogenetics) to scrutinize the olfactory system and to provide greater physiological precision for studying olfactory-driven behaviors. This review aims to present the most recent studies that have used light to activate components of the olfactory pathway, such as olfactory receptor neurons, or neurons located further downstream, while leaving intact others brain circuits. With the use of optogenetics to unravel the mystery of olfaction, scientists have begun to disentangle how the brain makes sense of smells. In this review, we shall discuss how the brain recognizes odors, how it memorizes them, and how animals make decisions based on odorants they are capable of sensing. Although this review deals with olfaction, the role of light will be central throughout. PMID- 27194793 TI - Synaptic activation of ribosomal protein S6 phosphorylation occurs locally in activated dendritic domains. AB - Previous studies have shown that induction of long-term potentiation (LTP) induces phosphorylation of ribosomal protein S6 (rpS6) in postsynaptic neurons, but the functional significance of rpS6 phosphorylation is poorly understood. Here, we show that synaptic stimulation that induces perforant path LTP triggers phosphorylation of rpS6 (p-rpS6) locally near active synapses. Using antibodies specific for phosphorylation at different sites (ser235/236 versus ser240/244), we show that strong synaptic activation led to dramatic increases in immunostaining throughout postsynaptic neurons with selectively higher staining for p-ser235/236 in the activated dendritic lamina. Following LTP induction, phosphorylation at ser235/236 was detectable by 5 min, peaked at 30 min, and was maintained for hours. Phosphorylation at both sites was completely blocked by local infusion of the NMDA receptor antagonist, APV. Despite robust induction of p-rpS6 following high frequency stimulation, assessment of protein synthesis by autoradiography revealed no detectable increases. Exploration of a novel environment led to increases in the number of p-rpS6-positive neurons throughout the forebrain in a pattern reminiscent of immediate early gene induction and many individual neurons that were p-rpS6-positive coexpressed Arc protein. Our results constrain hypotheses about the possible role of rpS6 phosphorylation in regulating postsynaptic protein synthesis during induction of synaptic plasticity. PMID- 27194794 TI - Influence of pharmacological manipulations of NMDA and cholinergic receptors on working versus reference memory in a dual component odor span task. AB - Developed as a tool to assess working memory capacity in rodents, the odor span task (OST) has significant potential to advance drug discovery in animal models of psychiatric disorders. Prior investigations indicate OST performance is impaired by systemic administration of N-methyl-d-aspartate receptor (NMDA-r) antagonists and is sensitive to cholinergic manipulations. The present study sought to determine whether an impairment in OST performance can be produced by systemic administration of the competitive NMDA-r antagonist 3-(2 carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP; 3, 10, 17 mg/kg i.p.) in a unique dual-component variant of the OST, and whether this impairment is ameliorated by nicotine (0.75 mg/kg i.p.). Male Sprague-Dawley rats were trained to asymptotic level of performance on a 24-trial two-comparison incrementing nonmatching to sample OST. In addition, rats were administered a two-comparison olfactory reference memory (RM) task, which was integrated into the OST. The RM task provided an assessment of the effects of drug administration on global behavioral measures, long-term memory and motivation. Several measures of working memory (span, longest run, and accuracy) were dose dependently impaired by CPP without adversely affecting RM. Analysis of drug effects across trial blocks demonstrated a significant impairment of performance even at low memory loads, suggesting a CPP-induced deficit of olfactory short-term memory that is not load dependent. Although nicotine did not ameliorate CPP-induced impairments in span or accuracy, it did block the impairment in longest run produced by the 10 mg/kg dose of CPP. Overall, our results indicate that performance in our 24 odor two comparison OST is capacity dependent and that CPP impaired OST working, but not reference, memory. PMID- 27194795 TI - Retrosplenial cortex is required for the retrieval of remote memory for auditory cues. AB - The restrosplenial cortex (RSC) has a well-established role in contextual and spatial learning and memory, consistent with its known connectivity with visuo spatial association areas. In contrast, RSC appears to have little involvement with delay fear conditioning to an auditory cue. However, all previous studies have examined the contribution of the RSC to recently acquired auditory fear memories. Since neocortical regions have been implicated in the permanent storage of remote memories, we examined the contribution of the RSC to remotely acquired auditory fear memories. In Experiment 1, retrieval of a remotely acquired auditory fear memory was impaired when permanent lesions (either electrolytic or neurotoxic) were made several weeks after initial conditioning. In Experiment 2, using a chemogenetic approach, we observed impairments in the retrieval of remote memory for an auditory cue when the RSC was temporarily inactivated during testing. In Experiment 3, after injection of a retrograde tracer into the RSC, we observed labeled cells in primary and secondary auditory cortices, as well as the claustrum, indicating that the RSC receives direct projections from auditory regions. Overall our results indicate the RSC has a critical role in the retrieval of remotely acquired auditory fear memories, and we suggest this is related to the quality of the memory, with less precise memories being RSC dependent. PMID- 27194797 TI - Late enrichment maintains accurate recent and remote spatial memory only in aged rats that were unimpaired when middle aged. AB - Exposure of rodents to a stimulating environment has beneficial effects on some cognitive functions that are impaired during physiological aging, and especially spatial reference memory. The present study investigated whether environmental enrichment rescues these functions in already declining subjects and/or protects them from subsequent decline. Subgroups of 17-mo-old female rats with unimpaired versus impaired performance in a spatial reference memory task (Morris water maze) were housed until the age of 24 mo in standard or enriched environment. They were then trained in a second reference memory task, conducted in a different room than the first, and recent (1 d) and remote (10 d) memory were assessed. In unimpaired subgroups, spatial memory declined from 17 to 24 mo in rats housed in standard conditions; an enriched environment during this period allowed maintenance of accurate recent and remote spatial memory. At 24 mo, rats impaired at the age of 17 mo housed in enriched environment learned the task and displayed substantial recent memory, but their performance remained lower than that of unimpaired rats, showing that enrichment failed to rescue spatial memory in already cognitively declining rats. Controls indicated carryover effects of the first water maze training, especially in aged rats housed in standard condition, and confirmed the beneficial effect of enrichment on remote memory of aged rats even if they performed poorly than young adults housed for the same duration in standard or enriched condition. PMID- 27194798 TI - The calmodulin-binding transcription activator CAMTA1 is required for long-term memory formation in mice. AB - The formation of long-term memory requires signaling from the synapse to the nucleus to mediate neuronal activity-dependent gene transcription. Synapse-to nucleus communication is initiated by influx of calcium ions through synaptic NMDA receptors and/or L-type voltage-gated calcium channels and involves the activation of transcription factors by calcium/calmodulin signaling in the nucleus. Recent studies have drawn attention to a new family of transcriptional regulators, the so-called calmodulin-binding transcription activator (CAMTA) proteins. CAMTAs are expressed at particularly high levels in the mouse and human brain, and we reasoned that, as calmodulin-binding transcription factors, CAMTAs may regulate the formation of long-term memory by coupling synaptic activity and calcium/calmodulin signaling to memory-related transcriptional responses. This hypothesis is supported by genetic studies that reported a correlation between Camta gene polymorphisms or mutations and cognitive capability in humans. Here, we show that acute knockdown of CAMTA1, but not CAMTA2, in the hippocampus of adult mice results in impaired performance in two memory tests, contextual fear conditioning and object-place recognition test. Short-term memory and neuronal morphology were not affected by CAMTA knockdown. Gene expression profiling in the hippocampus of control and CAMTA knockdown mice revealed a number of putative CAMTA1 target genes related to synaptic transmission and neuronal excitability. Patch clamp recordings in organotypic hippocampal slice cultures provided further evidence for CAMTA1-dependent changes in electrophysiological properties. In summary, our study provides experimental evidence that confirms previous human genetic studies and establishes CAMTA1 as a regulator of long-term memory formation. PMID- 27194796 TI - Motivational state, reward value, and Pavlovian cues differentially affect skilled forelimb grasping in rats. AB - Motor skills represent high-precision movements performed at optimal speed and accuracy. Such motor skills are learned with practice over time. Besides practice, effects of motivation have also been shown to influence speed and accuracy of movements, suggesting that fast movements are performed to maximize gained reward over time as noted in previous studies. In rodents, skilled motor performance has been successfully modeled with the skilled grasping task, in which animals use their forepaw to grasp for sugar pellet rewards through a narrow window. Using sugar pellets, the skilled grasping task is inherently tied to motivation processes. In the present study, we performed three experiments modulating animals' motivation during skilled grasping by changing the motivational state, presenting different reward value ratios, and displaying Pavlovian stimuli. We found in all three studies that motivation affected the speed of skilled grasping movements, with the strongest effects seen due to motivational state and reward value. Furthermore, accuracy of the movement, measured in success rate, showed a strong dependence on motivational state as well. Pavlovian cues had only minor effects on skilled grasping, but results indicate an inverse Pavlovian-instrumental transfer effect on movement speed. These findings have broad implications considering the increasing use of skilled grasping in studies of motor system structure, function, and recovery after injuries. PMID- 27194802 TI - Homeobox Is Pivotal for OsWUS Controlling Tiller Development and Female Fertility in Rice. AB - OsWUS has recently been shown to be a transcription factor gene critical for tiller development and fertility in rice. The OsWUS protein consists of three conserved structural domains, but their biological functions are still unclear. We discovered a new rice mutant resulting from tissue culture, which hardly produced tillers and exhibited complete female sterility. The male and female floral organs of the mutant were morphologically indistinguishable from those of the wild type. We named the mutant srt1 for completely sterile and reduced tillering 1. Map-based cloning revealed that the mutant phenotypes were caused by a mutation in OsWUS Compared with the two previously reported null allelic mutants of OsWUS (tab1-1 and moc3-1), which could produce partial N-terminal peptides of OsWUS, the srt1 protein contained a deletion of only seven amino acids within the conserved homeobox domain of OsWUS. However, the mutant phenotypes (monoculm and female sterility) displayed in srt1 were as typical and severe as those in tab1-1 and moc3-1 This indicates that the homeobox domain of SRT1 is essential for the regulation of tillering and sterility in rice. In addition, srt1 showed an opposite effect on panicle development to that of the two null allelic mutants, implying that the srt1 protein might still have partial or even new functions on panicle development. The results of this study suggest that the homeobox domain is pivotal for OsWUS function. PMID- 27194800 TI - Fruiting Body Formation in Volvariella volvacea Can Occur Independently of Its MAT-A-Controlled Bipolar Mating System, Enabling Homothallic and Heterothallic Life Cycles. AB - Volvariella volvacea is an important crop in Southeast Asia, but erratic fruiting presents a serious challenge for its production and breeding. Efforts to explain inconsistent fruiting have been complicated by the multinucleate nature, typical lack of clamp connections, and an incompletely identified sexual reproductive system. In this study, we addressed the life cycle of V. volvacea using whole genome sequencing, cloning of MAT loci, karyotyping of spores, and fruiting assays. Microscopy analysis of spores had previously indicated the possible coexistence of heterothallic and homothallic life cycles. Our analysis of the MAT loci showed that only MAT-A, and not MAT-B, controlled heterokaryotization. Thus, the heterothallic life cycle was bipolar. Karyotyping of single spore isolates (SSIs) using molecular markers supported the existence of heterokaryotic spores. However, most SSIs were clearly not heterokaryotic, yet contained structural variation (SV) markers relating to both alleles of both parents. Heterokaryons from crossed, self-sterile homokaryons could produce fruiting bodies, agreeing with bipolar heterothallism. Meanwhile, some SSIs with two different MAT-A loci also produced fruiting bodies, which supported secondary homothallism. Next, SSIs that clearly contained only one MAT-A locus (homothallism) were also able to fruit, demonstrating that self-fertile SSIs were not, per definition, secondary homothallic, and that a third life cycle or genetic mechanism must exist. Finally, recombination between SV markers was normal, yet 10 out of 24 SV markers showed 1:2 or 1:3 distributions in the spores, and large numbers of SSIs contained doubled SV markers. This indicated selfish genes, and possibly partial aneuploidy. PMID- 27194799 TI - Big insights from small volumes: deciphering complex leukocyte behaviors using microfluidics. AB - Inflammation is an indispensable component of the immune response, and leukocytes provide the first line of defense against infection. Although the major stereotypic leukocyte behaviors in response to infection are well known, the complexities and idiosyncrasies of these phenotypes in conditions of disease are still emerging. Novel tools are indispensable for gaining insights into leukocyte behavior, and in the past decade, microfluidic technologies have emerged as an exciting development in the field. Microfluidic devices are readily customizable, provide tight control of experimental conditions, enable high precision of ex vivo measurements of individual as well as integrated leukocyte functions, and have facilitated the discovery of novel leukocyte phenotypes. Here, we review some of the most interesting insights resulting from the application of microfluidic approaches to the study of the inflammatory response. The aim is to encourage leukocyte biologists to integrate these new tools into increasingly more sophisticated experimental designs for probing complex leukocyte functions. PMID- 27194803 TI - Construction and Annotation of a High Density SNP Linkage Map of the Atlantic Salmon (Salmo salar) Genome. AB - High density linkage maps are useful tools for fine-scale mapping of quantitative trait loci, and characterization of the recombination landscape of a species' genome. Genomic resources for Atlantic salmon (Salmo salar) include a well assembled reference genome, and high density single nucleotide polymorphism (SNP) arrays. Our aim was to create a high density linkage map, and to align it with the reference genome assembly. Over 96,000 SNPs were mapped and ordered on the 29 salmon linkage groups using a pedigreed population comprising 622 fish from 60 nuclear families, all genotyped with the 'ssalar01' high density SNP array. The number of SNPs per group showed a high positive correlation with physical chromosome length (r = 0.95). While the order of markers on the genetic and physical maps was generally consistent, areas of discrepancy were identified. Approximately 6.5% of the previously unmapped reference genome sequence was assigned to chromosomes using the linkage map. Male recombination rate was lower than females across the vast majority of the genome, but with a notable peak in subtelomeric regions. Finally, using RNA-Seq data to annotate the reference genome, the mapped SNPs were categorized according to their predicted function, including annotation of ~2500 putative nonsynonymous variants. The highest density SNP linkage map for any salmonid species has been created, annotated, and integrated with the Atlantic salmon reference genome assembly. This map highlights the marked heterochiasmy of salmon, and provides a useful resource for salmonid genetics and genomics research. PMID- 27194801 TI - Comparative Genomics of a Parthenogenesis-Inducing Wolbachia Symbiont. AB - Wolbachia is an intracellular symbiont of invertebrates responsible for inducing a wide variety of phenotypes in its host. These host-Wolbachia relationships span the continuum from reproductive parasitism to obligate mutualism, and provide a unique system to study genomic changes associated with the evolution of symbiosis. We present the genome sequence from a parthenogenesis-inducing Wolbachia strain (wTpre) infecting the minute parasitoid wasp Trichogramma pretiosum The wTpre genome is the most complete parthenogenesis-inducing Wolbachia genome available to date. We used comparative genomics across 16 Wolbachia strains, representing five supergroups, to identify a core Wolbachia genome of 496 sets of orthologous genes. Only 14 of these sets are unique to Wolbachia when compared to other bacteria from the Rickettsiales. We show that the B supergroup of Wolbachia, of which wTpre is a member, contains a significantly higher number of ankyrin repeat-containing genes than other supergroups. In the wTpre genome, there is evidence for truncation of the protein coding sequences in 20% of ORFs, mostly as a result of frameshift mutations. The wTpre strain represents a conversion from cytoplasmic incompatibility to a parthenogenesis-inducing lifestyle, and is required for reproduction in the Trichogramma host it infects. We hypothesize that the large number of coding frame truncations has accompanied the change in reproductive mode of the wTpre strain. PMID- 27194804 TI - The Rate and Spectrum of Spontaneous Mutations in Mycobacterium smegmatis, a Bacterium Naturally Devoid of the Postreplicative Mismatch Repair Pathway. AB - Mycobacterium smegmatis is a bacterium that is naturally devoid of known postreplicative DNA mismatch repair (MMR) homologs, mutS and mutL, providing an opportunity to investigate how the mutation rate and spectrum has evolved in the absence of a highly conserved primary repair pathway. Mutation accumulation experiments of M. smegmatis yielded a base-substitution mutation rate of 5.27 * 10(-10) per site per generation, or 0.0036 per genome per generation, which is surprisingly similar to the mutation rate in MMR-functional unicellular organisms. Transitions were found more frequently than transversions, with the A:T->G:C transition rate significantly higher than the G:C->A:T transition rate, opposite to what is observed in most studied bacteria. We also found that the transition-mutation rate of M. smegmatis is significantly lower than that of other naturally MMR-devoid or MMR-knockout organisms. Two possible candidates that could be responsible for maintaining high DNA fidelity in this MMR-deficient organism are the ancestral-like DNA polymerase DnaE1, which contains a highly efficient DNA proofreading histidinol phosphatase (PHP) domain, and/or the existence of a uracil-DNA glycosylase B (UdgB) homolog that might protect the GC rich M. smegmatis genome against DNA damage arising from oxidation or deamination. Our results suggest that M. smegmatis has a noncanonical Dam (DNA adenine methylase) methylation system, with target motifs differing from those previously reported. The mutation features of M. smegmatis provide further evidence that genomes harbor alternative routes for improving replication fidelity, even in the absence of major repair pathways. PMID- 27194805 TI - An Improved Binary Vector and Escherichia coli Strain for Agrobacterium tumefaciens-Mediated Plant Transformation. AB - The plasmid vector pGreenII is widely used to produce plant transformants via a process that involves propagation in Escherichia coli However, we show here that pGreenII-based constructs can be unstable in E. coli as a consequence of them hampering cell division and promoting cell death. In addition, we describe a new version of pGreenII that does not cause these effects, thereby removing the selective pressure for mutation, and a new strain of E. coli that better tolerates existing pGreenII-based constructs without reducing plasmid yield. The adoption of the new derivative of pGreenII and the E. coli strain, which we have named pViridis and MW906, respectively, should help to ensure the integrity of genes destined for study in plants while they are propagated and manipulated in E. coli The mechanism by which pGreenII perturbs E. coli growth appears to be dysregulation within the ColE1 origin of replication. PMID- 27194807 TI - Using Genotyping by Sequencing to Map Two Novel Anthracnose Resistance Loci in Sorghum bicolor. AB - Colletotrichum sublineola is an aggressive fungal pathogen that causes anthracnose in sorghum [Sorghum bicolor (L.) Moench]. The obvious symptoms of anthracnose are leaf blight and stem rot. Sorghum, the fifth most widely grown cereal crop in the world, can be highly susceptible to the disease, most notably in hot and humid environments. In the southeastern United States the acreage of sorghum has been increasing steadily in recent years, spurred by growing interest in producing biofuels, bio-based products, and animal feed. Resistance to anthracnose is, therefore, of paramount importance for successful sorghum production in this region. To identify anthracnose resistance loci present in the highly resistant cultivar 'Bk7', a biparental mapping population of F3:4 and F4:5 sorghum lines was generated by crossing 'Bk7' with the susceptible inbred 'Early Hegari-Sart'. Lines were phenotyped in three environments and in two different years following natural infection. The population was genotyped by sequencing. Following a stringent custom filtering protocol, totals of 5186 and 2759 informative SNP markers were identified in the two populations. Segregation data and association analysis identified resistance loci on chromosomes 7 and 9, with the resistance alleles derived from 'Bk7'. Both loci contain multiple classes of defense-related genes based on sequence similarity and gene ontologies. Genetic analysis following an independent selection experiment of lines derived from a cross between 'Bk7' and sweet sorghum 'Mer81-4' narrowed the resistance locus on chromosome 9 substantially, validating this QTL. As observed in other species, sorghum appears to have regions of clustered resistance genes. Further characterization of these regions will facilitate the development of novel germplasm with resistance to anthracnose and other diseases. PMID- 27194808 TI - Transcriptomic Analysis of Differentially Expressed Genes During Larval Development of Rapana venosa by Digital Gene Expression Profiling. AB - During the life cycle of shellfish, larval development, especially metamorphosis, has a vital influence on the dynamics, distribution, and recruitment of natural populations, as well as seed breeding. Rapana venosa, a carnivorous gastropod, is an important commercial shellfish in China, and is an ecological invader in the United States, Argentina, and France. However, information about the mechanism of its early development is still limited, because research in this area has long suffered from a lack of genomic resources. In this study, 15 digital gene expression (DGE) libraries from five developmental stages of R. venosa were constructed and sequenced on the IIIumina Hi-Sequation 2500 platform. Bioinformaticsanalysis identified numerous differentially and specifically expressed genes, which revealed that genes associated with growth, nervous system, digestive system, immune system, and apoptosis participate in important developmental processes. The functional analysis of differentially expressed genes was further implemented by gene ontology, and Kyoto encyclopedia of genes and genomes enrichment. DGE profiling provided a general picture of the transcriptomic activities during the early development of R. venosa, which may provide interesting hints for further study. Our data represent the first comparative transcriptomic information available for the early development of R. venosa, which is a prerequisite for a better understanding of the physiological traits controlling development. PMID- 27194809 TI - ForestPMPlot: A Flexible Tool for Visualizing Heterogeneity Between Studies in Meta-analysis. AB - Meta-analysis has become a popular tool for genetic association studies to combine different genetic studies. A key challenge in meta-analysis is heterogeneity, or the differences in effect sizes between studies. Heterogeneity complicates the interpretation of meta-analyses. In this paper, we describe ForestPMPlot, a flexible visualization tool for analyzing studies included in a meta-analysis. The main feature of the tool is visualizing the differences in the effect sizes of the studies to understand why the studies exhibit heterogeneity for a particular phenotype and locus pair under different conditions. We show the application of this tool to interpret a meta-analysis of 17 mouse studies, and to interpret a multi-tissue eQTL study. PMID- 27194806 TI - Analysis of Plasminogen Genetic Variants in Multiple Sclerosis Patients. AB - Multiple sclerosis (MS) is a prevalent neurological disease of complex etiology. Here, we describe the characterization of a multi-incident MS family that nominated a rare missense variant (p.G420D) in plasminogen (PLG) as a putative genetic risk factor for MS. Genotyping of PLG p.G420D (rs139071351) in 2160 MS patients, and 886 controls from Canada, identified 10 additional probands, two sporadic patients and one control with the variant. Segregation in families harboring the rs139071351 variant, identified p.G420D in 26 out of 30 family members diagnosed with MS, 14 unaffected parents, and 12 out of 30 family members not diagnosed with disease. Despite considerably reduced penetrance, linkage analysis supports cosegregation of PLG p.G420D and disease. Genotyping of PLG p.G420D in 14446 patients, and 8797 controls from Canada, France, Spain, Germany, Belgium, and Austria failed to identify significant association with disease (P = 0.117), despite an overall higher prevalence in patients (OR = 1.32; 95% CI = 0.93-1.87). To assess whether additional rare variants have an effect on MS risk, we sequenced PLG in 293 probands, and genotyped all rare variants in cases and controls. This analysis identified nine rare missense variants, and although three of them were exclusively observed in MS patients, segregation does not support pathogenicity. PLG is a plausible biological candidate for MS owing to its involvement in immune system response, blood-brain barrier permeability, and myelin degradation. Moreover, components of its activation cascade have been shown to present increased activity or expression in MS patients compared to controls; further studies are needed to clarify whether PLG is involved in MS susceptibility. PMID- 27194810 TI - Systematic Protein-Protein Interaction Analysis Reveals Intersubcomplex Contacts in the Nuclear Pore Complex. AB - The nuclear pore complex (NPC) enables transport across the nuclear envelope. It is one of the largest multiprotein assemblies in the cell, built from about 30 proteins called nucleoporins (Nups), organized into distinct subcomplexes. Structure determination of the NPC is a major research goal. The assembled ~40 112 MDa NPC can be visualized by cryoelectron tomography (cryo-ET), while Nup subcomplexes are studied crystallographically. Docking the crystal structures into the cryo-ET maps is difficult because of limited resolution. Further, intersubcomplex contacts are not well characterized. Here, we systematically investigated direct interactions between Nups. In a comprehensive, structure based, yeast two-hybrid interaction matrix screen, we mapped protein-protein interactions in yeast and human. Benchmarking against crystallographic and coaffinity purification data from the literature demonstrated the high coverage and accuracy of the data set. Novel intersubcomplex interactions were validated biophysically in microscale thermophoresis experiments and in intact cells through protein fragment complementation. These intersubcomplex interaction data provide direct experimental evidence toward possible structural arrangements of architectural elements within the assembled NPC, or they may point to assembly intermediates. Our data favors an assembly model in which major architectural elements of the NPC, notably the Y-complex, exist in different structural contexts within the scaffold. PMID- 27194811 TI - A continuous spectrophotometric assay that distinguishes between phospholipase A1 and A2 activities. AB - A new spectrophotometric assay was developed to measure, continuously and specifically, phospholipase A1 (PLA1) or phospholipase A2 (PLA2) activities using synthetic glycerophosphatidylcholines (PCs) containing alpha-eleostearic acid, either at the sn-1 position [1-alpha-eleostearoyl-2-octadecyl-rac-glycero-3 phosphocholine (EOPC)] or at the sn-2 position [1-octadecyl-2-alpha-eleostearoyl rac-glycero-3-phosphocholine (OEPC)]. The substrates were coated onto the wells of microtiter plates. A nonhydrolyzable ether bond, with a non-UV-absorbing alkyl chain, was introduced at the other sn position to prevent acyl chain migration during lipolysis. Upon enzyme action, alpha-eleostearic acid is liberated and then solubilized into the micellar phase. The PLA1 or PLA2 activity was measured by the increase in absorbance at 272 nm due to the transition of alpha eleostearic acid from the adsorbed to the soluble state. EOPC and OEPC differentiate, with excellent accuracy, between PLA1 and PLA2 activity. Lecitase((r)), guinea pig pancreatic lipase-related protein 2 (known to be a PLA1 enzyme), bee venom PLA2, and porcine pancreatic PLA2 were all used to validate the assay. Compared with current assays used for continuously measuring PLA1 or PLA2 activities and/or their inhibitors, the development of this sensitive enzymatic method, using coated PC substrate analogs to natural lipids and based on the UV spectroscopic properties of alpha-eleostearic acid, is a significant improvement. PMID- 27194812 TI - Targeting cAMP/PKA pathway for glycemic control and type 2 diabetes therapy. AB - In mammals, cyclic adenosine monophosphate (cAMP) is an intracellular second messenger that is usually elicited by binding of hormones and neurotransmitters to G protein-coupled receptors (GPCRs). cAMP exerts many of its physiological effects by activating cAMP-dependent protein kinase (PKA), which in turn phosphorylates and regulates the functions of downstream protein targets including ion channels, enzymes, and transcription factors. cAMP/PKA signaling pathway regulates glucose homeostasis at multiple levels including insulin and glucagon secretion, glucose uptake, glycogen synthesis and breakdown, gluconeogenesis, and neural control of glucose homeostasis. This review summarizes recent genetic and pharmacological studies concerning the regulation of glucose homeostasis by cAMP/PKA in pancreas, liver, skeletal muscle, adipose tissues, and brain. We also discuss the strategies for targeting cAMP/PKA pathway for research and potential therapeutic treatment of type 2 diabetes mellitus (T2D). PMID- 27194813 TI - Reply to 'Safety profile of capecitabine as maintenance treatment after XELOX or FOLFOX in metastatic colorectal cancer patients' by C. Cremolini et al. PMID- 27194814 TI - Targeted sequencing of BRCA1 and BRCA2 across a large unselected breast cancer cohort suggests that one-third of mutations are somatic. AB - BACKGROUND: A mutation found in the BRCA1 or BRCA2 gene of a breast tumor could be either germline or somatically acquired. The prevalence of somatic BRCA1/2 mutations and the ratio between somatic and germline BRCA1/2 mutations in unselected breast cancer patients are currently unclear. PATIENTS AND METHODS: Paired normal and tumor DNA was analyzed for BRCA1/2 mutations by massively parallel sequencing in an unselected cohort of 273 breast cancer patients from south Sweden. RESULTS: Deleterious germline mutations in BRCA1 (n = 10) or BRCA2 (n = 10) were detected in 20 patients (7%). Deleterious somatic mutations in BRCA1 (n = 4) or BRCA2 (n = 5) were detected in 9 patients (3%). Accordingly, about 1 in 9 breast carcinomas (11%) in our cohort harbor a BRCA1/2 mutation. For each gene, the tumor phenotypes were very similar regardless of the mutation being germline or somatically acquired, whereas the tumor phenotypes differed significantly between wild-type and mutated cases. For age at diagnosis, the patients with somatic BRCA1/2 mutations resembled the wild-type patients (median age at diagnosis, germline BRCA1: 41.5 years; germline BRCA2: 49.5 years; somatic BRCA1/2: 65 years; wild-type BRCA1/2: 62.5 years). CONCLUSIONS: In a population without strong germline founder mutations, the likelihood of a BRCA1/2 mutation found in a breast carcinoma being somatic was ~1/3 and germline 2/3. This may have implications for treatment and genetic counseling. PMID- 27194816 TI - Temporal dietary shift in jellyfish revealed by stable isotope analysis. AB - A temporal change in the stable isotope (SI) composition of jellyfish in the Kiel Fjord, Western Baltic Sea, was documented by analyzing delta13C, delta15N and delta34S of bell tissue of Aurelia aurita and Cyanea capillata in the period between June and October 2011. A strong and significant temporal change in all SI values of A. aurita was found, including an increase of ~3 0/00 in delta13C, a decrease of ~4 0/00 in delta15N and sharp decline of ~7 0/00 in delta34S. While knowledge gaps in jellyfish isotope ecology, in particular the lack of reliable trophic enrichment factors, call for a conservative interpretation of our data, observed changes in particular in delta34S, as indicated by means of a MixSIR mixing model, would be consistent with a temporal dietary shift in A. aurita from mesozooplankton (>150 um) to microplankton and small re-suspended particles (0.8 20 um) from the benthos. Presence of a hitherto unidentified food source not included in the model could also contribute to the shift. During the 2-month occurrence of C. capillata, its isotope composition remained stable and was consistent with a mainly mesozooplanktonic diet. Mixing model output, mainly driven by delta34S values, indicated a lower proportion of A. aurita in the diet of C. capillata than previously reported, and thus to a potentially lesser importance of intraguild predation among jellyfish in the Kiel Fjord. Overall, our results clearly highlighted the potential for substantial intraspecific isotopic seasonal variation in jellyfish, which should be taken into account in future feeding ecology studies on this group. PMID- 27194815 TI - A prognostic regulatory pathway in stage I epithelial ovarian cancer: new hints for the poor prognosis assessment. AB - BACKGROUND: Clinical and pathological parameters of patients with epithelial ovarian cancer (EOC) do not thoroughly predict patients' outcome. Despite the good outcome of stage I EOC compared with that of stages III and IV, the risk assessment and treatments are almost the same. However, only 20% of stage I EOC cases relapse and die, meaning that only a proportion of patients need intensive treatment and closer follow-up. Thus, the identification of cell mechanisms that could improve outcome prediction and rationalize therapeutic options is an urgent need in the clinical practice. PATIENTS AND METHODS: We have gathered together 203 patients with stage I EOC diagnosis, from whom snap-frozen tumor biopsies were available at the time of primary surgery before any treatment. Patients, with a median follow-up of 7 years, were stratified into a training set and a validation set. RESULTS AND CONCLUSIONS: Integrated analysis of miRNA and gene expression profiles allowed to identify a prognostic cell pathway, composed of 16 miRNAs and 10 genes, wiring the cell cycle, 'Activins/Inhibins' and 'Hedgehog' signaling pathways. Once validated by an independent technique, all the elements of the circuit resulted associated with overall survival (OS) and progression free survival (PFS), in both univariate and multivariate models. For each patient, the circuit expressions have been translated into an activation state index (integrated signature classifier, ISC), used to stratify patients into classes of risk. This prediction reaches the 89.7% of sensitivity and 96.6% of specificity for the detection of PFS events. The prognostic value was then confirmed in the external independent validation set in which the PFS events are predicted with 75% sensitivity and 94.7% specificity. Moreover, the ISC shows higher classification performance than conventional clinical classifiers. Thus, the identified circuit enhances the understanding of the molecular mechanisms lagging behind stage I EOC and the ISC improves our capabilities to assess, at the time of diagnosis, the patient risk of relapse. PMID- 27194817 TI - Be Careful Where You Smile: Culture Shapes Judgments of Intelligence and Honesty of Smiling Individuals. AB - Smiling individuals are usually perceived more favorably than non-smiling ones they are judged as happier, more attractive, competent, and friendly. These seemingly clear and obvious consequences of smiling are assumed to be culturally universal, however most of the psychological research is carried out in WEIRD societies (Western, Educated, Industrialized, Rich, and Democratic) and the influence of culture on social perception of nonverbal behavior is still understudied. Here we show that a smiling individual may be judged as less intelligent than the same non-smiling individual in cultures low on the GLOBE's uncertainty avoidance dimension. Furthermore, we show that corruption at the societal level may undermine the prosocial perception of smiling-in societies with high corruption indicators, trust toward smiling individuals is reduced. This research fosters understanding of the cultural framework surrounding nonverbal communication processes and reveals that in some cultures smiling may lead to negative attributions. PMID- 27194818 TI - Association of Common Variants in MMPs with Periodontitis Risk. AB - Background. Matrix metalloproteinases (MMPs) are considered to play an important role during tissue remodeling and extracellular matrix degradation. And functional polymorphisms in MMPs genes have been reported to be associated with the increased risk of periodontitis. Recently, many studies have investigated the association between MMPs polymorphisms and periodontitis risk. However, the results remain inconclusive. In order to quantify the influence of MMPs polymorphisms on the susceptibility to periodontitis, we performed a meta analysis and systematic review. Results. Overall, this comprehensive meta analysis included a total of 17 related studies, including 2399 cases and 2002 healthy control subjects. Our results revealed that although studies of the association between MMP-8 -799 C/T variant and the susceptibility to periodontitis have not yielded consistent results, MMP-1 (-1607 1G/2G, -519 A/G, and -422 A/T), MMP-2 (-1575 G/A, -1306 C/T, -790 T/G, and -735 C/T), MMP-3 (-1171 5A/6A), MMP-8 (-381 A/G and +17 C/G), MMP-9 (-1562 C/T and +279 R/Q), and MMP-12 (-357 Asn/Ser), as well as MMP-13 (-77 A/G, 11A/12A) SNPs are not related to periodontitis risk. Conclusions. No association of these common MMPs variants with the susceptibility to periodontitis was found; however, further larger-scale and multiethnic genetic studies on this topic are expected to be conducted to validate our results. PMID- 27194820 TI - The Diagnostic Value of the Pleural Fluid C-Reactive Protein in Parapneumonic Effusions. AB - Purpose. The aim of this study was to evaluate the sensitivity of pleural C reactive protein (CRP) biomarker levels in identifying parapneumonic effusions. Methods. A single-center, retrospective review of 244 patients diagnosed with pleural effusions was initiated among patients at the Rabin Medical Center, Petah Tikva, Israel, between January 2011 and December 2013. The patients were categorized into 4 groups according to their type of pleural effusion as follows: heart failure, malignant, post-lung transplantation, and parapneumonic effusion. Results. The pleural CRP levels significantly differentiated the four groups (p < 0.001) with the following means: parapneumonic effusion, 5.38 +/- 4.85 mg/dL; lung transplant, 2.77 +/- 2.66 mg/dL; malignancy, 1.19 +/- 1.51 mg/dL; and heart failure, 0.57 +/- 0.81 mg/dL. The pleural fluid CRP cut-off value for differentiating among parapneumonic effusions and the other 3 groups was 1.38 mg/dL. The sensitivity, specificity, positive predictive value, and negative predictive value were 84.2%, 71.5%, 37%, and 95%, respectively. A backward logistic regression model selected CRP as the single predictor of parapneumonic effusion (OR = 1.59, 95% CI = 1.37-1.89). Conclusions. Pleural fluid CRP levels can be used to distinguish between parapneumonic effusions and other types of exudative effusions. CRP levels < 0.64 mg/dL are likely to indicate a pleural effusion from congestive heart failure, whereas levels >= 1.38 mg/dL are suggestive of an infectious etiology. PMID- 27194819 TI - Postnatal Changes in Humerus Cortical Bone Thickness Reflect the Development of Metabolic Bone Disease in Preterm Infants. AB - Objective. To use cortical bone thickness (CBT) of the humerus to identify risk factors for the development of metabolic bone disease in preterm infants. Methods. Twenty-seven infants born at <32 weeks of gestational age, with a birth weight of <1,500 g, were enrolled. Humeral CBT was measured from chest radiographs at birth and at 27-28, 31-32, and 36-44 weeks of postmenstrual age (PMA). The risk factors for the development of osteomalacia were statistically analyzed. Results. The humeral CBT at 36-44 weeks of PMA was positively correlated with gestational age and birth weight and negatively correlated with the duration of mechanical ventilation. CBT increased with PMA, except in six very early preterm infants in whom it decreased. Based on logistic regression analysis, gestational age and duration of mechanical ventilation were identified as risk factors for cortical bone thinning. Conclusions. Humeral CBT may serve as a radiologic marker of metabolic bone disease at 36-44 weeks of PMA in preterm infants. Cortical bones of extremely preterm infants are fragile, even when age is corrected for term, and require extreme care to lower the risk of fractures. PMID- 27194821 TI - How to reduce the costs of ornaments without reducing their effectiveness? An example of a mechanism from carotenoid-based plumage. AB - ABSTRACT: Carotenoid-based ornaments are often considered to be honest indicators of individual quality assessed by potential mates. However, males can use a variety of strategies that minimize the amount of costly carotenoids used while retaining the effectiveness of color signaling. Birds could do this by altering pigment intake, metabolism, or its presentation to a potential signal receiver. Here, we propose a new mechanism of lowering the costs of carotenoid displays in birds: differential allocation of pigments within single feathers. We studied the coloration of the yellow terminal tail bands of rectrices of male Bohemian waxwings. Using reflectance spectrometry, we show that the two central rectrices are most intensively colored compared to other rectrices. More detailed analyses reveal that these differences result from feather-specific patterns of rectrices coloration. The outer feather vanes of the outermost rectrices are more intensively colored compared to the inner vanes. However, the central rectrices have equally colored vanes that are, on average, more intensively pigmented than the outermost rectrices. When the waxwing tail is folded, the outermost rectrices are covered by other feathers, except for the narrow, outer vane. Central rectrices, however, form the outermost layers which are not obscured by other tail feathers. Thus, the feather vanes that are the most visible to potential viewers are also the most pigmented. These results support the occurrence of a previously overlooked mechanism to reduce the costs of carotenoid-based ornaments: precise pigment distribution to maximize efficiency of signals within single feathers. SIGNIFICANCE STATEMENT: Males of many bird species use bright carotenoid-based plumage coloration to attract females. These traits are physiologically expensive such that only individuals in prime condition can develop the most vivid colors. Males often "cheat" to obtain attractive appearances at lower costs. We showed that this goal could be achieved by differential deposition of pigments into the most conspicuous feather regions. Bohemian waxwing males have yellow tips on their rectrices of which the outer vanes are more brightly colored compared to the inner vanes. These inner feather vanes are usually covered by other feathers and are, thus, less visible to conspecifics. The only exception is the pair of central rectrices that are fully exposed, and both feather vanes are equally colored. In this species, males minimize the use of costly carotenoid pigments while maintaining elaborate ornamentation of plumage regions that are most visible to potential mates. PMID- 27194822 TI - Intergroup encounters in Verreaux's sifakas (Propithecus verreauxi): who fights and why? AB - ABSTRACT: Individuals living in groups have to achieve collective action for successful territorial defense. Because conflicts between neighboring groups always involve risks and costs, individuals must base their decision to participate in a given conflict on an evaluation of the trade-off between potential costs and benefits. Since group members may differ in motivation to engage in group encounters, they exhibit different levels of participation in conflicts. In this study, we investigated factors influencing participation in intergroup encounters in Verreaux's sifakas (Propithecus verreauxi), a group living primate from Madagascar. Over a period of 12 months, we studied eight adjacent sifaka groups in Kirindy Forest. We observed 71 encounters between known neighboring groups in which adult females and males participated equally as often. No individual participated in every encounter, and non-participation occurred more often in larger groups. Females participated less often in encounters when they had dependent infants, presumably to reduce the risk of infanticide. Male participation was influenced by social status: dominant males participated in most encounters, whereas males with fewer opportunities to reproduce participated less often, hence male participation is influenced by the incentive of maintaining access to females. The number of actively participating individuals in the opponent group positively influenced the participation in both sexes. Thus, sifakas seem to decide joining a given encounter opportunistically, most likely based on a combination of individual incentives and the actual circumstance of each encounter, suggesting that the complexity in intergroup relationships appears to be the product of decisions made by each individual group member. SIGNIFICANCE STATEMENT: Cooperation among group-living animals is often challenged by collective action problems resulting from individual differences in interests in contributing to collective behaviors. Intergroup encounters involve distinguished costs and benefits for each individual despite being in the same social group. Therefore, encounters between groups offer a good opportunity to investigate individual participation in collective action. In this study, we investigate the influence of different incentives on individual participation in intergroup encounters in wild Malagasy primate, Verreaux's sifakas. We propose a novel approach that takes into account the variable circumstances of each conflict, such as the number of individuals fighting in both groups as a predictor for participation. We believe that our study not only provides novel data on wild sifakas, but it also offers new perspectives for the interpretation of intergroup relationships in other taxa. PMID- 27194824 TI - Floral Sonication is an Innate Behaviour in Bumblebees that can be Fine-Tuned with Experience in Manipulating Flowers. AB - Bumblebees demonstrate an extensive capacity for learning complex motor skills to maximise exploitation of floral rewards. This ability is well studied in nectar collection but its role in pollen foraging is less well understood. Floral sonication is used by bees to extract pollen from some plant species with anthers which must be vibrated (buzzed) to release pollen. Pollen removal is determined by sonication characteristics including frequency and amplitude, and thus the ability to optimise sonication should allow bees to maximise the pollen collection. We investigated the ability of the buff-tailed bumblebee (Bombus terrestris) to modify the frequency and amplitude of their buzzes with increasing experience manipulating flowers of the buzz-pollinated plant Solanum rostratum. We analysed flight and feeding vibrations generated by naive workers across feeding bouts. Feeding buzzes were of a higher frequency and a lower amplitude than flight buzzes. Both flight and feeding buzzes had reduced amplitudes with increasing number of foraging trips. However, the frequency of their feeding buzzes was reduced significantly more than their flight buzzes as bumblebee workers gained experience manipulating flowers. These results suggest that bumblebees are able to modify the characteristics of their buzzes with experience manipulating buzz-pollinated flowers. We discuss our findings in the context of bumblebee learning, and the current understanding of the optimal sonication characteristics for releasing pollen in buzz-pollinated species. Our results present a tantalising insight into the potential role of learning in floral sonication, paving the way for future research in this area. PMID- 27194823 TI - Effect of Therapeutic Touch in Patients with Cancer: a Literature Review. AB - BACKGROUND: The use of complementary and alternative medicine (CAM) techniques has been growing. The National Center for Complementary and Alternative Medicine places therapeutic touch (TT) into the category of bio field energy. This literature review is aimed at critically evaluating the data from clinical trials examining the clinical efficacy of therapeutic touch as a supportive care modality in adult patients with cancer. METHODS: Electronic databases (PubMed, Scopus, Scholar Google, and Science Direct) were searched from the year 1990 to 2015 to locate potentially relevant peer-reviewed articles using the key words therapeutic touch, touch therapy, neoplasm, cancer, and CAM. Additionally, relevant journals and references of all the located articles were manually searched for other potentially relevant studies. RESULTS: The number of 334 articles was found on the basis of the key words, of which 17 articles related to the clinical trial were examined in accordance with the objectives of the study. A total of 6 articles were in the final dataset in which several examples of the positive effects of healing touch on pain, nausea, anxiety and fatigue, and life quality and also on biochemical parameters were observed. CONCLUSION: Based on the results of this study, an affirmation can be made regarding the use of TT, as a non-invasive intervention for improving the health status in patients with cancer. Moreover, therapeutic touch was proved to be a useful strategy for adult patients with cancer. PMID- 27194825 TI - e-Cadherin in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Induced Parkinson Disease. AB - Today a large number of studies are focused on clarifying the complexity and diversity of the pathogenetic mechanisms inducing Parkinson disease. We used 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a neurotoxin that induces Parkinson disease, to evaluate the change of midbrain structure and the behavior of the anti-inflammatory factor e-cadherin, interleukin-6, tyrosine hydroxylase, phosphatase and tensin homolog, and caveolin-1. The results showed a strong expression of e-cadherin, variation of length and thickness of the heavy neurofilaments, increase of interleukin-6, and reduction of tyrosine hydroxylase known to be expression of dopamine cell loss, reduction of phosphatase and tensin homolog described to impair responses to dopamine, and reduction of caveolin-1 known to be expression of epithelial-mesenchymal transition and fibrosis. The possibility that the overexpression of the e-cadherin might be implicated in the anti-inflammatory reaction to MPTP treatment by influencing the behavior of the other analyzed molecules is discussed. PMID- 27194826 TI - Th17 Cell Response in SOD1G93A Mice following Motor Nerve Injury. AB - An increased risk of ALS has been reported for veterans, varsity athletes, and professional football players. The mechanism underlying the increased risk in these populations has not been identified; however, it has been proposed that motor nerve injury may trigger immune responses which, in turn, can accelerate the progression of ALS. Accumulating evidence indicates that abnormal immune reactions and inflammation are involved in the pathogenesis of ALS, but the specific immune cells involved have not been clearly defined. To understand how nerve injury and immune responses may contribute to ALS development, we investigated responses of CD4(+) T cell after facial motor nerve axotomy (FNA) at a presymptomatic stage in a transgenic mouse model of ALS (B6SJL SOD1(G93A)). SOD1(G93A) mice, compared with WT mice, displayed an increase in the basal activation state of CD4(+) T cells and higher frequency of Th17 cells, which were further enhanced by FNA. In conclusion, SOD1(G93A) mice exhibit abnormal CD4(+) T cell activation with increased levels of Th17 cells prior to the onset of neurological symptoms. Motor nerve injury exacerbates Th17 cell responses and may contribute to the development of ALS, especially in those who carry genetic susceptibility to this disease. PMID- 27194828 TI - Plasma cell-rich acute rejection: A morphologic archetype of combined cellular and humoral rejection? PMID- 27194827 TI - Bigelovii A Protects against Lipopolysaccharide-Induced Acute Lung Injury by Blocking NF-kappaB and CCAAT/Enhancer-Binding Protein delta Pathways. AB - Optimal methods are applied to acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS), but the mortality rate is still high. Accordingly, further studies dedicated to identify novel therapeutic approaches to ALI are urgently needed. Bigelovii A is a new natural product and may exhibit anti inflammatory activity. Therefore, we sought to investigate its effect on lipopolysaccharide- (LPS-) induced ALI and the underlying mechanisms. We found that LPS-induced ALI was significantly alleviated by Bigelovii A treatment, characterized by reduction of proinflammatory mediator production, neutrophil infiltration, and lung permeability. Furthermore, Bigelovii A also downregulated LPS-stimulated inflammatory mediator expressions in vitro. Moreover, both NF kappaB and CCAAT/enhancer-binding protein delta (C/EBPdelta) activation were obviously attenuated by Bigelovii A treatment. Additionally, phosphorylation of both p38 MAPK and ERK1/2 (upstream signals of C/EBPdelta activation) in response to LPS challenge was also inhibited by Bigelovii A. Therefore, Bigelovii A could attenuate LPS-induced inflammation by suppression of NF-kappaB, inflammatory mediators, and p38 MAPK/ERK1/2-C/EBPdelta, inflammatory mediators signaling pathways, which provide a novel theoretical basis for the possible application of Bigelovii A in clinic. PMID- 27194829 TI - Th1, Th2 and Treg/T17 cytokines in two types of proliferative glomerulonephritis. AB - IgA nephropathy (IgAN) and focal segmental necrotizing glomerulonephritis (FSNGN) are characterized by proliferation of native glomerular cells and infiltration by inflammatory cells. Several cytokines act as mediators of kidney damage in both diseases. The aim of the present study was to investigate the role of Th1, Th2 and Treg/T17 cytokines in these types of proliferative glomerulonephritis. Simultaneous measurement of Th1 interleukin (IL-2, IL-12, tumor necrosis factor alpha [TNF-alpha], interferon-gamma [INF-gamma]), Th2 (IL-4, IL-5, IL-6, IL-10, IL-13), Treg/T17 transforming growth factor-beta 1 (TGF-beta1, granulocyte macrophage colony-stimulating factor [GM-CSF], IL-17) cytokines and C-C chemokines Monocyte chemoattractant protein-1 (MCP-1, macrophage inflammatory protein-1 [MIP-1] beta) was performed in first-morning urine samples, at the day of renal biopsy, using a multiplex cytokine assay. Cytokine concentrations were correlated with histological findings and renal function outcome. Urinary excretion of Th1, Th2 and Treg/Th17 cytokines were significantly higher in FSNGN compared to IgAN patients. In IgAN patients (n = 50, M/F: 36/14, M age: 40.7 [17 67] years), Th1, Th2 and T17 cytokines correlated significantly with the presence of endocapillary proliferation, while in FSNGN patients (n = 40, M/F: 24/16, M age: 56.5 [25-80] years), MCP-1 and TGF-beta1 had a positive correlation with severe extracapillary proliferation (P = 0.001 and P = 0.002, respectively). Urinary IL-17 was the only independent parameter associated with endocapillary proliferation in IgAN and with MCP-1 urinary excretion in FSNGN. Response to treatment was mainly predicted by IL-6 in IgAN, and by Th2 (IL-4, IL-6), Treg (GM CSF) cytokines and MIP-1 beta in FSNGN. Th1, Th2 and T17 cytokines were directly implicated in renal pathology in IgAN and possibly through MCP-1 production in FSNGN. IL-17 and IL-6 seem to have a central role in inflammation and progression of kidney injury. PMID- 27194830 TI - Nephroprotective effect of estrogen and progesterone combination on cisplatin induced nephrotoxicity in ovariectomized female rats. AB - Recently, we reported that estrogen (Es) has no beneficial effect on cisplatin (CP)-induced nephrotoxicity, but the role of progesterone (Pr) and the combination of Es and Pr are not yet well-defined. In this study, we investigated the protective role of Pr, and co-administration of Es/Pr on CP-induced nephrotoxicity. Eighty-six ovariectomized female Wistar rats were divided into 13 groups, and the experiments were performed in two phases. In Phase I, Groups 1-4 received 2, 5, 10, and 25 mg/kg, IM Pr dissolved in sesame oil every 5 days for four doses. Groups 5-8 had the same treatment regimen as Groups 1-4, but after the third injection the animals also received continuous dose of CP (2.5 mg/kg/day, i.p.) for 8 days. Group 9, as the positive control group, received sesame oil instead of Pr plus CP. Group 10, as the negative control group, received sesame oil instead of Pr. After the most effective dose of Pr was determined in Phase I, Groups 11-13 in Phase II received 10 mg/kg Pr plus either 0.25, 0.5, or 1 mg/kg, IM estradiol valerate every 5 days for four doses. After the third injection, they also received a continuous dose of CP for 8 days. The levels of blood urea nitrogen (BUN) and creatinine (Cr), kidney tissue damage score (KTDS), and kidney weight (KW) increased and body weight (BW) decreased in the positive control group (P < 0.05). Administration of Pr (10 mg/kg) plus CP decreased KTDS and BW loss and KW. Co-administration of ES/Pr at specific doses improved Cr, BUN, and KTDS; and resulted in reduced CP-induced nephrotoxicity. The results obtained suggest that the beneficial effect of Pr on CP-induced nephrotoxicity is dose-dependent. In addition, combination of Es/Pr with a specific dose decreased CP-induced nephrotoxicity. PMID- 27194831 TI - Expanding the antibody-mediated component of plasma cell-rich acute rejection: A case series. AB - Renal allograft rejection is mediated by T-cells (T-cell mediated rejection) or by donor-specific antibodies (DSAs) (antibody mediated rejection, ABMR). Plasma cell-rich acute rejection (PCAR) is a unique entity due to its peculiar morphology and poor prognostic behavior. All allograft biopsies done at our center from January 2013 to October 2014 were reviewed, and seven were identified with a diagnosis of PCAR with antibody mediated rejection (ABMR). The allograft biopsies were classified as per the Banff 2007 schema. Immunohistochemistry with C4d, SV 40, CD3, CD20, CD138, kappa and lambda light chain was performed. Total 210 allograft biopsies were performed in the study period of which seven biopsies (3.3%) were diagnosed as PCAR with ABMR. All these were late ABMRs (more than 6 months) with median posttransplant duration of 17 months. The allograft biopsy showed features of PCAR along with glomerulitis, peritubular capillaritis, and positive C4d. DSA was positive in six patients. All the patients were treated with standard therapeutic measures of acute cellular rejection (ACR) and ABMR including steroids, plasma exchange, rituximab and intravenous immunoglobulins. All the patients had persistent graft dysfunction or graft loss on follow-up. PMID- 27194832 TI - Unmasking of complements using proteinase-K in formalin fixed paraffin embedded renal biopsies. AB - Renal biopsy interpretation requires histopathology, direct immunofluorescence (DIF) and electron microscopy. Formalin-fixed, paraffin-embedded tissue (FFPE) sent for light microscopy can be used for DIF after antigen retrieval. However, complement staining has not been satisfactory. We standardized DIF using proteinase-K for antigen retrieval in FFPE renal biopsies. A pilot study was conducted on known cases of membranous glomerulonephritis (MGN), membranoproliferative type-1 (MPGN-1), immunoglobulin A nephropathy (IgAN), and anti-glomerular basement disease (anti-GBM). Immunofluorescence panel included fluorescein isothiocyanate (FITC) conjugated IgG, IgA, IgM, complements (C3 and C1q), light chains (kappa, lambda) and fibrinogen antibodies. After standardization of the technique, 75 renal biopsies and 43 autopsies cases were stained. Out of 43 autopsy cases, immune-complex mediated glomerulonephritis (GN) was confirmed in 18 cases (Lupus nephritis-11, IgAN-6, MGN-1), complement mediated dense deposit disease (DDD-1) and monoclonal diseases in 4 cases (amyloidosis-3, cast nephropathy-1). Immune-mediated injury was excluded in 17 cases (focal segmental glomerulosclerosis -3, crescentic GN-6 [pauci-immune-3, anti-GBM-3], thrombotic microangiopathy-5, atherosclerosis-3). Renal biopsies (n 75) where inadequate or no frozen sample was available; this technique classified 52 mesangiocapillary pattern as MPGN type-1-46, DDD-2 and (C3GN-4). Others were diagnosed as IgAN-3, lupus nephritis-2, MGN-4, diffuse proliferative glomerulonephritis (DPGN)-1, Non-IC crescentic GN-1, monoclonal diseases-3. In nine cases, DIF on FFPE tissue could not help in making diagnosis. Proteinase-K enzymatic digestion of FFPE renal biopsies can unmask complements (both C3 and C1q) in immune-complexes mediated and complement-mediated diseases. This method showed good results on autopsy tissues archived for as long as 15 years. PMID- 27194833 TI - A histopathological outlook on nephrotic syndrome: A pediatric perspective. AB - The developing world is observing changing histopathological patterns of idiopathic nephrotic syndrome (INS). However, the true burden of non-minimal change disease (non-MCD) presenting as INS remains unestimated owing to a paucity of data on renal biopsies. Data were collected from January 2006 to June 2014 on 75 children up to 16 years of age who underwent renal biopsies for INS. Mean age at biopsy was 11.2 +/- 3.7 years. The male to female ratio was 1.5:1. A total of 25 (33.3%) children were steroid sensitive, 36 (48%) were steroid resistant, 10 (13.3%) were steroid dependent and 4 (5.3%) came with relapse of nephrotic syndrome (NS). Focal segmental glomerulosclerosis (FSGS) was the most common histopathological subtype observed in 35 (46.8%) children followed by membranous glomerulonephritis (MGN) in 11 (14.7%), membranoproliferative glomerulonephritis (MPGN) and mesangioproliferative glomerulonephritis (MSGN) in 4 (5.3%) each and IgA nephropathy in one (1.3%). MCD was the histological lesion in 19 (25.3%) children. The histopathology established FSGS as the main underlying cause of steroid resistant NS. The study highlights the emergence of non-MCD as the common cause of INS in the pediatric population and signifies the importance of renal biopsies in children with INS. PMID- 27194834 TI - Diabetes, hypertension, sanitation, and health education by high school students in Guyana, South America. AB - We initiated a program for early detection of diabetes and hypertension, the main causes of kidney failure in Guyana, South America. We trained local high school students with the goal that these students would stay in the villages for long term, become health advocates and shift the reliance away from physicians. This project involved 7 high school students who were taught to monitor the health of one village of 1000-1500 population each. The program will be implemented for 3 years in which the entire population of seven villages (approximately 10,000 people) will be covered. This represents 1.3% population in Guyana. We present data from the pilot study from the sample of 619 people. The prevalence of diabetes mellitus was 13.9%. Among diabetics, 33.7% were using insulin and 86% oral hypoglycemic agents. Prevalence of hypertension was 29.4%, 63.2% were overweight and 17% were obese. About 9.9% patients were unaware about the existence of hypertension. We have shown in our study that high school students can be used to collect health data and monitor diabetes and hypertension. There was also a significant incidence of undetected diabetes and hypertension. PMID- 27194835 TI - Frequency of kidney diseases and clinical indications of pediatric renal biopsy: A single center experience. AB - Kidney biopsy occupies a fundamental position in the management of kidney diseases. There are very few renal pathology studies available in the literature from developing world. This study scrutinized the frequency and clinicopathological relationship of kidney biopsies done at the kidney center from 1997 to 2013 amongst pediatric patients. Kidney allograft biopsy were excluded. The specimen was examined under light microscopy and immunofluorescence while electron microscopy was not done. The study includes 423 patients, mean age was 10.48 +/- 4.58 years, males 245 (57.9%) were more than females 178 (42.1%). Nephrotic syndrome 314 (74.2%) was the most common clinical presentation followed by acute nephritic syndrome 35 (8.3%) and acute renal failure 24 (5.7%). Primary glomerulonephritis (PGN) was the most common group of diseases, seen in 360 (85.1%) followed by secondary glomerulonephritis (SGN) in 27 (6.4%) and tubulointerstitial nephritis in 21 (5.0%). Among PGN, minimal change disease (MCD) was the most dominant disease, with 128 (30.3%) cases followed by focal segmental glomerulosclerosis FSGS in 109 (25.8%) and membranous glomerulonephropathy in 27 (6.4%). Lupus nephritis (LN) was the leading cause of glomerular disease in SGN followed by hemolytic uremic syndrome. In conclusion, MCD is the most common histological finding, especially in younger children and FSGS is second to it. SGN is rare, and the most common disease in this category is LN while tubulointerstitial and vascular diseases are infrequent. PMID- 27194837 TI - Cerebral venous thrombosis in a patient with acute postinfectious glomerulonephritis. AB - Thrombosis of the cerebral venous sinuses (CVT) is described in nephrotic syndrome. A 13-year-old girl was admitted with acute post-infectious glomerulonephritis (APIGN). Subsequently she developed recurrent seizures with focal neurological deficits. On evaluation, she was found to have CVT. To the best of our knowledge, this is the first report of CVT in APIGN. Identifying this complication is imperative, as timely diagnosis and treatment could be lifesaving. PMID- 27194836 TI - Acute kidney injury and disseminated intravascular coagulation due to mercuric chloride poisoning. AB - Mercury is a toxic heavy metal and occurs in organic and inorganic forms. Inorganic mercury includes elemental mercury and mercury salts. Mercury salts are usually white powder or crystals, and widely used in indigenous medicines and folk remedies in Asia. Inorganic mercury poisoning causes acute kidney injury (AKI) and gastrointestinal manifestations and can be life-threatening. We describe a case with unknown substance poisoning who developed AKI and disseminated intravascular coagulation (DIC). Renal biopsy showed acute tubular necrosis. Later, the consumed substance was proven to be mercuric chloride. His renal failure improved over time, and his creatinine normalized after 2 months. PMID- 27194838 TI - Role of diffusion weighted imaging in diagnosis of post transplant lymphoproliferative disorders: Case reports and review of literature. AB - Post transplant lymphoproliferative disorder include a spectrum of conditions occurring in immunosuppressed post transplant recipients, lymphoma being the most ominous. (18)F-fludeoxyglucose positron emission tomography with computed tomography CT) is the current imaging gold standard for lymphoma imaging as it allows both morphological and functional assessment. CT and/or conventional magnetic resonance imaging (MRI) are used for morphological evaluation in transplant recipients. Integrating diffusion weighted imaging with apparent diffusion coefficient analysis in MRI protocol enhances its sensitivity and may prove invaluable in response assessment in transplant recipients. PMID- 27194839 TI - Ledipasvir and sofosbuvir for treatment of post- renal transplant hepatitis C infection: A case report with review of literature. AB - Liver disease due to hepatitis C infection in renal transplant recipients is difficult to treat and often associated with reduced patient survival. A 43-year old male, a renal allograft recipient, presented at 6 years follow-up with significant weight loss over 3 months. He was detected to have new onset diabetes mellitus together with hepatitis C virus (HCV) infection (genotype 1). His HCV load remained high despite the change of immuno-suppression from tacrolimus to cyclosporine. A decision to treat with a new anti-viral combination of ledipasvir and sofosbuvir for 12 weeks was taken. Within 3 weeks, his raised serum transaminases levels normalized and viral load became undetectable. At the end of 16 weeks, he continues to do well with normal renal function, has sustained remission from hepatitis C infection and resolution of diabetes. PMID- 27194840 TI - A rare case of phaeohyphomycosis caused by Fonsecaea pedrosoi in a child with nephrotic syndrome. AB - Dematiaceous fungi are the etiological agents of phaeohyphomycosis and are now increasingly being recognized for causing disease in humans. A high level of suspicion and routine fungal cultures are required to identify these cases. There is no consensus regarding their management. Here, an unusual presentation of phaeohyphomycosis (secondary to Fonsecaea pedrosoi) presenting as a disseminated infection in a case of nephrotic syndrome is described. PMID- 27194841 TI - Dense renal medulla sign. PMID- 27194842 TI - Whole body calcification in a hemodialysis patient. PMID- 27194843 TI - Bartter's syndrome in a geriatric patient. PMID- 27194844 TI - Chronic kidney disease of unknown etiology: Is time for prevention. PMID- 27194845 TI - Goodpasture's disease in a patient with Kartagener's syndrome: An unusual association. PMID- 27194846 TI - Digital gangrene in a child with atypical hemolytic uremic syndrome associated with anti-factor H antibodies. PMID- 27194847 TI - Crossed fused renal ectopia with Wolffian duct anomaly. PMID- 27194848 TI - Renal cortical necrosis: A life-threatening manifestation of primary antiphospholipid antibody syndrome. PMID- 27194849 TI - Message from IAOMP president. PMID- 27194850 TI - Message from IAOMP secretary. PMID- 27194851 TI - Message from IAOMP treasurer. PMID- 27194852 TI - From the Editor's desk. PMID- 27194853 TI - CANCER CONUNDRUM. PMID- 27194854 TI - Toto bodies. PMID- 27194855 TI - Do the presence of Barr bodies in male jail inmates indicates criminality: A pilot study. AB - BACKGROUND: Cytogenetic studies from past decades have shown that interphase cells of female cats contain a densely stained chromatin mass in their nuclei called as Barr bodies (BBs) named after the scientist Murray Barr. BBs are unique chromatin structures formed due to the condensation of the X-chromosome. Many psychopathic disorders originate from defective genes including the multiple X syndromes. Males with extra X-chromosome generally present with severe personality disorder. The present study was conducted to determine the presence of extra X-chromosome in male jail inmates through the detection of BB in peripheral blood and buccal smear. MATERIALS AND METHODS: Study included 100 male subjects (fifty jail inmates and fifty controls), after obtaining the consent, peripheral blood smears (PBS) and buccal smears (BS) were prepared and stained using Leishman's and cresyl violet stain respectively. One hundred neutrophils in PBS and epithelial cells in BS were screened for detection of the BB; accumulated data were tabulated and statistically analyzed using t-test and Chi-square test. RESULTS: 60% of cases in PBS and 36% in BS showed positivity for the presence of BB in jail inmates as compared to 14% of cases in PBS and none in BS were positive for BB in controls. CONCLUSION: Presence of BB in male suggests increased likelihood of criminal tendencies. Further studies are to be carried out to compare the results with karyotyping. PMID- 27194856 TI - Long-term effect of tobacco on unstimulated salivary pH. AB - AIMS AND OBJECTIVES: The aim of this study was to analyze and compare the effects of tobacco on salivary pH between tobacco chewers, smokers and controls. MATERIALS AND METHODS: A total of 60 subjects (males and females) aged 25-40 years, were divided equally into three groups: Tobacco smokers (Group A), chewers (Group B) and controls (Group C). Saliva of each subject was collected under resting condition. Salivary pH was determined using the specific salivary pH meter. RESULTS: The mean (+/-standard deviation) pH for Group A was 6.75 (+/ 0.11), Group B was 6.5 (+/-0.29) and Group C was 7.00 (+/-0.28) after comparison. The significant results showed lower salivary pH in Groups A and B as compared to controls. Salivary pH was lowest in Group B compared to Group A and Group C. CONCLUSION: This study indicates that a lower (acidic) salivary pH was observed in tobacco users as compared with control. These alterations in pH due to the long-term effect of tobacco use can render oral mucosa vulnerable to various oral and dental diseases. PMID- 27194857 TI - Mounting ground sections of teeth: Cyanoacrylate adhesive versus Canada balsam. AB - INTRODUCTION: Hard tissues can be studied by either decalcification or by preparing ground sections. Various mounting media have been tried and used for ground sections of teeth. However, there are very few studies on the use of cyanoacrylate adhesive as a mounting medium. AIMS: The aim of our study was to evaluate the efficacy of cyanoacrylate adhesive (FevikwikTM) as a mounting medium for ground sections of teeth and to compare these ground sections with those mounted with Canada balsam. MATERIALS AND METHODS: Ground sections were prepared from twenty extracted teeth. Each section was divided into two halves and mounted on one slide, one with cyanoacrylate adhesive (FevikwikTM) and the other with Canada balsam. Scoring for various features in the ground sections was done by two independent observers. STATISTICAL ANALYSIS USED: Statistical analysis using Student's t-test (unpaired) of average scores was performed for each feature observed. RESULTS: No statistically significant difference was found between the two for most of the features. However, cyanoacrylate was found to be better than Canada balsam for observing striae of Retzius (P < 0.0205), enamel lamellae (P < 0.036), dentinal tubules (P < 0.0057), interglobular dentin (P < 0.0001), sclerotic dentin - transmitted light (P < 0.00001), sclerotic dentin - polarized light (P < 0.0002) and Sharpey's fibers (P < 0.0004). CONCLUSIONS: This initial study shows that cyanoacrylate is better than Canada balsam for observing certain features of ground sections of teeth. However, it remains to be seen whether it will be useful for studying undecalcified sections of carious teeth and for soft tissue sections. PMID- 27194858 TI - A correlative study of the levels of salivary Streptococcus mutans, lactobacilli and Actinomyces with dental caries experience in subjects with mixed and permanent dentition. AB - PURPOSE: The aim of the study was to estimate the salivary levels of Streptococcus mutans, Lactobacilli and Actinomyces and to correlate it with dental caries experience in mixed and permanent dentition. MATERIALS AND METHODS: The sample size comprised 110 subjects. The decayed, missing and filled teeth (DMFT) index of all the individuals participating in the study was calculated. Saliva samples were collected from patients and samples were inoculated on specific culture media and incubated for a period of 48 h. Based on colony characteristics, S. mutans, Lactobacilli and Actinomyces were identified. RESULTS: A positive correlation exists between DMFT and S. mutans, Lactobacilli and Actinomyces in mixed dentition and permanent dentition group samples (P < 0.001). CONCLUSION: The conclusion from the results obtained was that S. Mutans, lactobacilli and Actinomyces which are the components of the normal microbial flora of the oral cavity play an important role in the pathogenesis of dental caries and increased number of microorganisms is associated with an increased caries frequency. PMID- 27194859 TI - Immunohistochemical expression of p53 and its clinicopathological correlation with modified Anneroth's histological grading system. AB - INTRODUCTION AND OBJECTIVES: Oral squamous cell carcinoma (OSCC) is an epithelial neoplasm generally beginning as focal overgrowth of altered stem cells near the basement membrane, moving upward and laterally, replacing the normal epithelium. Histopathological grading has been used for many decades in an attempt to predict the clinical behavior of oral squamous cell carcinoma. In the present study, Forty biopsies were studied for histological grading and p53 expression. The p53 expression was studied in relation to clinical parameters such as age, sex of patient and site of tumors. Relation between histological grade of malignancy and p53 protein expression was analysed. All cases were classified according to Anneroth's histological malignancy grading system (1987). MATERIALS AND METHODS: 40 cases of OSCC were assessed for clinical parameters, Anneroth's histological grading and immunohistochemically stained with p53 protien. STATISTICAL ANALYSIS: The results obtained were analyzed using Spearman's Co-relation. OBSERVATIONS AND RESULTS: The positive expression of p53 was found in 62% of carcinomas studied. Positivity of p53 showed correlation with histological grade of malignancy and with individual parameters like degree of keratinization, nuclear polymorphism, number of mitoses and lymphoplasmacytic infiltration while showed a negative correlation with pattern of invasion. CONCLUSION: Our study showed a significant correlation between parameters of tumor cell population, lymphoplasmacytic infiltration and p53 expression. A significant association between high grade of malignancy and p53 overexpression and insignificant correlation of p53 with age, sex of the patient and site of the tumor was found. PMID- 27194860 TI - Aggrandizing oral submucous fibrosis grading using an adjunct special stain: A pilot study. AB - INTRODUCTION: Oral submucous fibrosis (OSMF) is graded according to various histological factors which include the epithelial changes and the connective tissue changes. These features though could be identified in routine hematoxylin and eosin (H and E) staining; they could be better appreciated in special stains. This pilot study is an attempt to identify a single special stain that can act as an adjunct to H and E stain to help grade this potentially malignant disease. AIMS AND OBJECTIVES: To assess if special stains can improvise on differentiating the various histological changes seen in OSMF and to accordingly grade OSMF cases. MATERIALS AND METHODS: Formalin-fixed paraffin-embedded tissue sections of OSMF-10 cases of each grade (n = 30). Three special stains: Van-Gieson, Mallory's trichrome and Masson trichrome. STATISTICAL ANALYSIS: The results obtained were tabulated and statistically analyzed using Chi-square test. OBSERVATIONS AND RESULTS: The thickness and degree of keratinization were best detected in Mallory's stain (100%) and were statistically significant; the subepithelial changes were better detected using special stains, especially Mallory's stain (100%). The changes in collagen fibers were better visualized in all three special stains but were not statistically significant. The changes in blood vessels were better detected in Van-Gieson's and Mallory's stain; the obtained results were statistically significant. The degree of fibrosis between muscle bundles could be detected in all the three special stains, but when compared the results were not statistically significant. The questionable areas of muscle degeneration, especially in deeper connective tissue were better detected in Mallory's (43%) and Masson's stain (43%) as compared to Van-Gieson stain (14%) and the results obtained were statistically significant. The inflammatory cells and dysplastic features are better visualized in routine H and E stains. CONCLUSION: Pathogenesis of OSMF is related to fibro-elastic and muscle degenerative changes in the connective tissue followed by secondary changes in epithelium. Routine H and E, stains all the connective tissue components in various shades of pink, use of special stains bestows contrast between different components of connective tissue, thus improvising grading of OSMF. Mallory's stain can be used as a single adjunct to H and E stain as both pattern of keratinization in the epithelium and changes in the superficial and deeper connective tissue could be ascertained. PMID- 27194861 TI - Immunohistochemical detection of the receptor activator of nuclear factor Kappa B ligand and c-fos in giant cell granuloma. AB - BACKGROUND: Giant cell granuloma (GCG) is an intraosseous giant cell fibroblastic lesion that predominantly affects the jaw bones in children and adults. Despite its frequent local progression and destructive effect, it is traditionally considered reparative or reactive in nature. The receptor activator of nuclear factor Kappa B ligand (RANKL), a member of the tumor necrosis factor family and the transcription factor c-fos play a major role in osteoclast proliferation and differentiation. In this study, we examined the expression of RANKL and c-fos in lesional tissues from seven patients with GCG. MATERIALS AND METHODS: Automated immunohistochemical staining was performed on formalin-fixed paraffin-embedded sections from 7 cases, using antibodies against RANKL, c-fos and p53. RESULTS: All tissues showed nuclear staining for c-fos and cytoplasmic staining for RANKL. The staining was strong, diffuse and observed in both mononuclear lesional cells and giant cells. No staining was observed with p53. CONCLUSION: Expression of RANKL and c-fos in this lesion, similar to what has been reported in giant cell tumors of bone, suggests a similar pathogenesis and hence a potential response to anti-RANKL inhibitors. A larger study is needed to confirm these findings and define the relationship of this lesion to other giant cell-rich bone lesions. PMID- 27194862 TI - Quantitative evaluation of microvessel density using CD34 in clinical variants of ameloblastoma: An immunohistochemical study. AB - BACKGROUND: Odontogenic epithelium plays an important role in the histogenesis of odontogenic tumors of the jaws. Ameloblastomas, which arise from odontogenic epithelium, are considered benign with little tendency to metastasize. Tumors require an adequate supply of oxygen and a way to remove their waste products. This can be achieved by angiogenesis. In situ quantification of the microvessel density (MVD) is a usual method for assessing angiogenesis. Moreover, angiogenesis may differ in subtypes of ameloblastomas and could play a role in determining the pattern of tumor growth. AIM: The aim of the present study was to demonstrate the expression of cluster of differentiation (CD34) in variants of ameloblastomas and to correlate and compare their expression to the aggressive behavior. MATERIALS AND METHODS: A retrospective cross-sectional study which included forty paraffin blocks was conducted after obtaining ethical committee clearance. Ten cases of pyogenic granuloma were used as a positive control and thirty cases were of solid multicystic ameloblastoma (SMA), unicystic ameloblastoma (UA) and desmoplastic ameloblastomas. Angiogenesis was assessed using CD34 antigen and was immunohistochemically localized. Statistical analysis was carried out for comparative analysis with the help of ANOVA test, Kolmogorov Smirnov test and least significance difference test. RESULTS: A significant correlation was obtained between the MVD of all the three variants, i.e., SMA, UA and desmoplastic ameloblastomas which was statistically significant (P < 0.05). CONCLUSION: Increased MVD in the three variants, i.e., SMA, UA and desmoplastic ameloblastoma seen in the present study could suggest that the angiogenesis has an important role in tumor progression and aggressiveness of ameloblastomas. PMID- 27194863 TI - Role of preprocedural rinse and high volume evacuator in reducing bacterial contamination in bioaerosols. AB - CONTEXT: Microbial contamination, which occurs during dental procedures, has been a potential threat to dental professionals and individuals. There has been a growing concern over the role of bioaerosols in spread of various airborne infections and also to reduce the risk of bioaerosol contamination. AIMS: This study was to analyze the number of colony forming units (CFUs) in bioaerosols generated during ultrasonic scaling procedure as well as to evaluate the efficacy of chlorhexidine 0.12% (CHX) preprocedural mouth rinse and high volume evacuator (HVE) in minimizing the bioaerosol contamination. METHODS: About 45 individuals were divided into three Groups A, B and C. These groups underwent ultrasonic scaling before and after the use of CHX (0.12%), HVE and combination of CHX (0.12%) and HVE. Bioaerosols were collected on blood agar plates which were incubated at 37 degrees C for 48 h, and the CFUs were counted with manual colony counting device. A comparison was also done between A versus B, B versus C and A versus C groups. STATISTICAL ANALYSIS USED: Student's t-test. RESULTS: We found a significant reduction in the CFUs when CHX (0.12%) preprocedural rinse (P < 0), or HVE (P < 0.001) or combination of both CHX (0.12%) and HVE were employed (P < 0.001). Maximum reduction in CFUs was observed when CHX (0.12%) and HVE were used in combination as compared to their individual use. A moderate significance was seen between A versus C groups but not with B versus C groups and A versus B groups. CONCLUSION: From our study, we conclude that individual methods such as CHX (0.12%) and HVE were useful to reduce the dental bioaerosols; however, combination of both CHX (0.12%) and HVE is more efficient to reduce dental bioaerosols than individual method. PMID- 27194864 TI - Salivary alkaline phosphatase levels speak about association of smoking, diabetes and potentially malignant diseases??? AB - BACKGROUND: Alkaline phosphatase (ALP) is a hydrolase intracellular enzyme participating in the metabolic processes of cells. Rise in salivary ALP (S-ALP) levels reflects inflammation and destruction of healthy tissues suggesting it as a clinical biomarker. S-ALP is used in analyzing the severity of the disease occurrence in smokers and nonsmokers who are diabetic and nondiabetic. S-ALP levels are analyzed using autoanalyzer in 40 patients who visited our department. AIMS AND OBJECTIVES: To determine the levels of S-ALP in diagnosing potentially malignant conditions and debilitating diseases in early stages of inflammation and altered cellular metabolism. MATERIALS AND METHODS: The study groups include: (1) Group A - 10 smokers who are diabetic. (2) Group B - 10 smokers who are nondiabetic. (3) Group C - 10 nonsmokers who are diabetic. (4) Group D - 10 nonsmokers and nondiabetic as control. Unstimulated saliva samples are collected and run in auto-analyzer with ALP enzyme reagent to analyze ALP levels. Comparison is made between all the four groups. RESULTS: Results were statistically significant with increased activity of ALP levels in saliva from Group A when compared to Group D. The results are Group A > Group B > Group C > Group D. The results also revealed significant raise in levels of ALP levels in saliva from smokers when compared to diabetes. Thus explaining adverse effects of smoking. CONCLUSION: S-ALP can be considered to be the biomarker for evaluating adverse effects of smoking, diabetes and other debilitating diseases in early stages. PMID- 27194865 TI - Immunohistochemical expression of budding uninhibited by benzimidazole related 1 in leukoplakia and oral squamous cell carcinoma. AB - BACKGROUND: Budding uninhibited by benzimidazole related 1 (BUBR1) is an important protein in the mitotic spindle assembly checkpoint. Alterations in expression of BUBR1 have been reported in many premalignant and malignant lesions. AIM: To compare the expression of BUBR1 with respect to the normal mucosa and degree of dysplasia in oral leukoplakia (OL) and also with respect to different histopathological grades of oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Neutral buffered formalin-fixed and paraffin-embedded biopsy specimens 30 each of normal, OL and OSCC tissue were included in this study. The expression of BUBR1 was detected using immunohistochemistry (IHC). The scores obtained were subjected to ANOVA test. RESULTS: Significant correlation was found in immunostaining between normal, dysplasia and OSCC groups with a P value of 0.00001. The expression of BUBR1 was significant when compared with different degrees of dysplasia and in different histopathological grades of OSCC with a P value of 0.00001. CONCLUSION: Higher IHC scores were obtained with increased histopathological grades of OL and OSCC suggesting its role as a prognostic indicator. PMID- 27194866 TI - A 5 year retrospective study of biopsied jaw lesions with the assessment of concordance between clinical and histopathological diagnoses. AB - INTRODUCTION: The jaw can be affected by several lesions that manifest in the oral cavity, but little is known about their distribution patterns in various populations. AIMS AND OBJECTIVES: This study presents the frequency and distribution of biopsied jaw lesions recorded in Faculty of Dentistry and gathers the information including provisional and final diagnosis of the lesions. MATERIAL AND METHODS: Biopsy of 1938 lesions (2008-2013) was reviewed and 1473 lesions were included in this study. The provisional diagnosis and histopathological validations of lesions were compared. Data on the location of the lesion, as well as patient demographics, were also evaluated. The lesions were divided into three major groups as 1 - developmental/reactive and inflammatory lesions of the jaw, 2 - cystic lesion and 3 - tumor and tumor-like lesions. STATISTICAL ANALYSIS: The variables were recorded and analysed using descriptive statistics. RESULTS AND OBSERVATIONS: Three hundred and ninety-six lesions were in Group 1 and periapical granuloma was the most frequent diagnosis. Seven hundred and eighty-nine lesions were in Group 2 and the radicular cyst was the most frequent diagnosis. Two hundred and eighty-eight lesions were in Group 3 and the keratocystic odontogenic tumor was the most frequent. Two hundred and ninety-one biopsied lesions were in disagreement with respect to the diagnoses on clinical and histopathological examination. CONCLUSION: Consequently, a provisional diagnosis of some of the malignant lesions was reactive, inflammatory, cystic or benign lesions, therefore the importance of evaluation of the specimen is emphasized. PMID- 27194867 TI - Economic methods used in fabrication of tissue microarray: A pilot study. AB - BACKGROUND AND OBJECTIVE: Tissue microarray (TMA) is a method of harvesting small disks of tissue from a range of standard paraffin tissue blocks and placing them in an array on a recipient paraffin block such that hundreds of cases can be analyzed simultaneously by using only a few microliters of antibody in immunohistochemistry as a single experiment. The TMA construction done with the help of automated tissue arrayer or commercially available rubber molds are expensive. This study involved the fabrication of TMA using rubber-based additional silicone mold constructed in the department and comparison of this method with two other methods of fabricating TMA. MATERIALS AND METHODS: The TMA mold was fabricated using silicone material in the department. The recipient blocks were prepared. The tissue core prepared from donor blocks were inserted into the recipient blocks. The sections taken from this were compared with the TMA using double-sided adhesive tape technique and TMA by punching out holes in prefabricated dummy paraffin recipient block for insertion of tissue core. RESULTS: The TMA using a mold made of silicone showed more advantages than other two methods. CONCLUSION: Fabricating TMA mold using silicone in the department is inexpensive and yet efficient. PMID- 27194868 TI - Correlation of mast cells in different stages of human periodontal diseases: Pilot study. AB - AIMS AND OBJECTIVES: The aim of this study was to evaluate and correlate the relationship between mast cells counts and different stages of human periodontal diseases. MATERIALS AND METHODS: The study sample comprised 50 patients, which were divided into three groups, consisting of 10 cases of clinically healthy gingival tissues (control group) 20 cases of dental plaque-induced gingivitis with no attachment loss and 20 cases of localized chronic periodontitis (LCP) characterized by the loss of periodontal support. The samples for control group were obtained during tooth extractions for orthodontic reasons. The specimens were immediately fixed in 10% neutral buffered formalin. CONCLUSION: In this study, LCP cases had higher mast cell counts compared to gingivitis sites or healthy tissues. Increased mast cell counts in the progressing sites of periodontal diseases may indicate the importance of these cells in the progression of chronic periodontitis. PMID- 27194869 TI - Expression of human telomerase reverse transcriptase protein in oral epithelial dysplasia and oral squamous cell carcinoma: An immunohistochemical study. AB - BACKGROUND: Telomerase is an RNA-dependent DNA polymerase that synthesizes TTAGGG telomeric DNA sequences and almost universally provides the molecular basis for unlimited proliferative potential. The telomeres become shorter with each cycle of replication and reach a critical limit; most cells die or enter stage of replicative senescence. Telomere length maintenance by telomerase is required for all the cells that exhibit limitless replicative potential. It has been postulated that reactivation of telomerase expression is necessary for the continuous proliferation of neoplastic cells to attain immortality. Use of immunohistochemistry (IHC) is a useful, reliable method of localizing the human telomerase reverse transcriptase (hTERT) protein in tissue sections which permits cellular localization. Although there exists a lot of information on telomerase in oral cancer, little is known about their expression in oral epithelial dysplasia and their progression to oral squamous cell carcinoma (OSCC) compared to normal oral mucosa. This study addresses this lacuna. AIMS: To compare the expression of hTERT protein in oral epithelial dysplasia and OSCC with normal oral mucosa by Immunohistochemical method. SUBJECTS AND METHODS: In this preliminary study, IHC was used to detect the expression of hTERT protein in OSCC (n = 20), oral epithelial dysplasia (n = 21) and normal oral mucosa (n = 10). The tissue localization of immunostain, cellular localization of immunostain, nature of stain, intensity of stain, percentage of cells stained with hTERT protein were studied. A total number of 100 cells were counted in each slide. STATISTICAL ANALYSIS: All the data were analyzed using SPSS software version 16.0. The tissue localization, cellular localization of cytoplasmic/nuclear/both of hTERT stain, staining intensity was compared across the groups using Pearson's Chi-square test. The mean percentage of cells stained for oral epithelial dysplasia, OSCC and normal oral mucosa were compared using analysis of variance (ANOVA). A P < 0.05 was considered to be statistically significant. RESULTS: The mean hTERT positive cells in the study groups were as follows, 62.91% in normal oral mucosa samples, 77.06% in oral epithelial dysplasia cases, and 81.48% in OSCC. In 61.9% of oral epithelial dysplasia and 65% of OSCC in our study, staining was visualized within the nucleus predominantly in the dot like pattern. There was a statistically significant difference in the nature of nuclear stain between oral epithelial dysplasia and OSCC (P = 0.023). CONCLUSIONS: Our results suggests that the mean percentage of cells showing hTERT expression steadily increased from normal oral mucosa to oral epithelial dysplasia to OSCC. The steady trend of increase in the percentage of cells was evident in different grades of oral epithelial dysplasia group and OSCC. The nature of hTERT staining did show variations among the three groups and promise to be a potential surrogate marker for malignant transformation. Further studies using IHC on larger sample size and clinical follow-up of these patients will be ascertaining the full potential of hTERT as a surrogate marker of epithelial transformation. PMID- 27194870 TI - Pyruvic acid levels in serum and saliva: A new course for oral cancer screening? AB - OBJECTIVE: Cancerous cells show increased glycolysis rate. This will increase overall levels of pyruvate as it is one of the end products of glycolysis. The present on-going study is to estimate the levels of pyruvate in saliva and serum among healthy and oral cancer subjects. SETTINGS AND DESIGN: Hospital-based cross sectional comparative study. METHODOLOGY: A total of 50 subjects among healthy and oral cancer subjects were selected based on clinical and histological criteria. Saliva and serum samples were collected and subjected to pyruvate level estimation using biochemical analysis. STATISTICAL ANALYSIS: Descriptive analysis and Mann-Whitney test were used to find the statistical difference between the two independent groups. RESULTS: Serum pyruvic acid levels of the healthy group were 1.09 +/- 0.14 and for oral cancer, it was 2.95 +/- 0.59 and salivary level were 3.49 +/- 0.47 and 1.32 +/- 0.10 respectively. Mann-Whitney test showed statistically significant difference in serum and salivary pyruvate level in between two groups (P < 0.000 respectively). CONCLUSION: The present study showed noticeable variation in the level of pyruvic acid among healthy and oral cancer subjects. This generates the hypothesis that estimation of the pyruvic acid can be a new tool to screening of the cancer. PMID- 27194871 TI - Role of human papillomavirus and tumor suppressor genes in oral cancer. AB - The incidence of oral cancer remains high and is associated with many deaths in both Western and Asian countries. Several risk factors for the development of oral cancer are now well known, including smoking, drinking and consumption of smokeless tobacco products. Genetic predisposition to oral cancer has been found in certain cases, but its components are not yet entirely clear. In accordance with the multi-step theory of carcinogenesis, the natural history of oral cancer seems to gradually evolve through transitional precursor lesions from normal epithelium to a full-blown metastatic phenotype. A number of genomic lesions accompany this transformation and a wealth of related results has appeared in recent literature and is being summarized here. Furthermore, several key genes have been implicated, especially well-known tumor suppressors such as the cyclin dependent kinase inhibitors, TP53 and RB1 and oncogenes such as the cyclin family, epidermal growth factor receptor and RAS. Viral infections, particularly oncogenic human papillomavirus subtypes and Epstein-Barr virus, can have a tumorigenic effect on oral epithelia and their role is discussed, along with potential therapeutic interventions. A brief explanatory theoretical model of oral carcinogenesis is provided and potential avenues for further research are highlighted. PMID- 27194872 TI - Prions in dentistry: A need to be concerned and known. AB - Prion diseases were first discovered by Stanley B. Prusiner who defined prions as infectious, transmissible proteinaceous particles that lack nucleic acid and are composed exclusively of a modified isoform of the noninfectious cellular prion protein (PrPC). These are incurable neurodegenerative conditions affecting both animals and humans. They may be sporadic, infectious or inherited in origin. Human prion diseases include Creutzfeldt-Jakob desease (CJD), Gerstmann- Straussler-Scheinker disease, Kuru and Fatal familial insomnia. Prions resist the conventional sterilization procedures and hence the dentists must be aware of such diseases so as to opt standard methods of infection control and decontamination for such infectious agents. This review article divulge the dentists with a brief overview of the characteristics of prions, the risk of transmission and the implications for infection control in dentist. PMID- 27194873 TI - Molecular markers in oral lichen planus: A systematic review. AB - Oral lichen planus (OLP) is a chronic inflammatory mucosal disease that is usually detected in 0.5-2.2% of the human population. Among these, only 0.5-2.9% of the lesions progress to carcinoma. However, there are no prognostic markers available presently to recognize the increased risk in malignant transformation of the lesions. Selected markers for cell proliferation, adhesion, apoptosis and lymphocytic infiltration were analyzed by immunohistochemistry in addition to static cytometry for DNA content. The concept linking OLP and oral squamous cell carcinoma states that chronic inflammation results in crucial DNA damage, which further progresses to development of carcinoma. Even though in the past decade, enormous information has been accumulated on malignant potential of OLP, its transformation still remains unclear. Hence, the purpose of this article was to review cellular and molecular markers to understand the pathogenesis of OLP and its progression toward malignancy. PMID- 27194875 TI - A rare spindle-cell variant of non-Hodgkin's lymphoma of the mandible. AB - A 64-year-old male farmer presented with a rapidly progressive swelling of the left mandible since 6 months. The swelling was firm to hard, diffuse, nontender, obliterating the vestibule with paresthesia of lower lip. The cone beam computed tomography imaging revealed an ill-defined, moth-eaten radiolucency with destruction of the buccal and lingual cortical plates. The rapid growth and aggressive behavior of the lesion coupled with guidance from the patient's previous reports from the incisional biopsy and fine needle aspiration cytology warranted a mandibular resection. Microscopic examination showed an encapsulated lesion situated in the connective tissue containing a mixture of proliferating spindle-shaped cells arranged in fascicles and round cells infiltrating into the connective tissue stroma and bone. The neoplastic cells exhibited atypical features such as pleomorphism, hyperchromatism and increased mitotic figures with noncleaved nuclei. A working diagnosis of a spindle-cell sarcoma was arrived at with various differentials provided such as fibrosarcoma, rhabdomyosarcoma, leiomyosarcoma, malignant peripheral nerve sheath tumor, Langerhans cell histiocytosis and lymphoma and stating the need for immunohistochemistry to subtype the tumor. The neoplastic cells were negative for Van Gieson's stain and Masson's trichrome. Immunohistochemical analysis performed using desmin, smooth muscle actin, S-100 and CD1a in a bid to determine the phenotype of the tumor and rule out the previously stated differentials were all negative for the lesion. Lymphoid markers such as leukocyte common antigen and CD20 (cluster differentiation marker for B-cells) showed positivity in spindle-shaped cells as well as round cells indicating the tumor to be a lymphoproliferative lesion of B cell type. A final diagnosis of "spindle-cell variant of non-Hodgkin's lymphoma" was rendered based on the immunohistochemical profile. PMID- 27194874 TI - Epigenetics: A possible answer to the undeciphered etiopathogenesis and behavior of oral lesions. AB - Much controversy has existed over the etiopathogenesis and management of oral lesions, especially oral malignancies. The knowledge of genetic basis is proving to be inadequate in the light of emerging new mechanisms termed epigenetic phenomena. The present review article aims to understand the role of epigenetic mechanisms in oral lesions. Epigenetics is the study of acquired changes in chromatin structure that arise independently of a change in the underlying deoxyribonucleic acid (DNA) nucleotide sequence. Key components involved in epigenetic regulation are DNA methylation, histone modifications and modifications in micro ribonucleic acids (miRNA). Epigenetics is a reversible system that can be affected by various environmental factors such as diet, drugs, mental stress, physical activity and addictive substances such as tobacco, nicotine and alcohol. Epigenetics may also play a role in explaining the etiopathogenesis of developmental anomalies, genetic defects, cancer as well as substance addiction (tobacco, cigarette and alcohol). Epigenetic modifications may contribute to aberrant epigenetic mechanisms seen in oral precancers and cancers. In the near future, epigenetic variations found in oral dysplastic cells can act as a molecular fingerprint for malignancies. The literature in English language was searched and a structured scientific review and meta-analysis of scientific publications from the year 2000 to year 2015 was carried out from various journals. It was observed that epigenetic marks can prove to be novel markers for early diagnosis, prognosis and treatment of oral cancers as well as other oral diseases. PMID- 27194876 TI - Precursor B-cell lymphoblastic lymphoma of oral cavity: A case report with its diagnostic workup. AB - Lymphoblastic lymphoma (LBL), seen primarily in children or young adults, is a malignant neoplasia that originates from B or T lymphocyte precursors and rarely occurs in the oral cavity. In this localization, neither the clinical features nor the radiologic appearances are pathognomic and can pose significant diagnostic problems. Histopathologically, it presents as a round blue cell tumor. An early and accurate diagnosis of this entity is very important due to its high cure rate. We report a case of B-cell LBL involving oral cavity in a 10-year-old child. The purpose of this report is to explore the diagnostic workup. PMID- 27194877 TI - Epithelioid hemangioendothelioma of the mandibular gingiva: A rare case of metastasis 4 years after radical excision and literature review. AB - Malignant epithelioid hemangioendothelioma (MEH), or high-risk epithelioid hemangioendothelioma, is a low- to intermediate-grade vascular malignancy. A few cases of MEH have been documented in the head and neck region, including the neck, thyroid gland, larynx and scalp. MEHs are extremely rare in the oral cavity. Only 31 cases of MEH in the oral cavity were described in English literature between 1975 and 2014. Further, only eleven cases were referred to MEH of the maxillary or mandibular gingiva. No gingival MEH metastases have been described in literature. We report a literature review and a case of MEH with a metastatic occurrence 4 years after surgical excision. PMID- 27194878 TI - Basal cell adenoma of maxillary sinus mimicking ameloblastoma. AB - Basal cell adenoma (BCA) is a rare basaloid tumor, with only 20% of cases occurring in minor salivary glands. Histologically, BCA is characterized by the presence of basaloid cells and may frequently be mistaken with canalicular adenoma, basal cell adenocarcinoma, adenoid cystic carcinoma and basaloid squamous cell carcinoma. Immunohistochemistry may aid in arriving at a final diagnosis as in the present case. Reported here is a case of locally aggressive BCA. Histologically, the lesion mimicked ameloblastoma and other entities which posed a diagnostic challenge. There are no reports of BCA presenting as an aggressive lesion available in English literature so far; moreover, merely a single case of BCA of maxillary sinus has been previously reported to the best of our cognition. This case report highlights the rarity of this tumor with regards to its site of origin, clinical behavior and histopathological mimics. PMID- 27194880 TI - Extraskeletal myxoid chondrosarcoma of maxilla: A rare entity. PMID- 27194879 TI - Sinonasal teratocarcinosarcoma: Case report of an unusual neoplasm. AB - Sinonasal teratocarcinosarcoma is an extremely rare malignant tumor arising in the sinonasal tract, having combined histological features of teratoma and carcinosarcoma. Here, we are presenting a case of sinonasal teratocarcinosarcoma in a 28-year-old male patient. A 28-year-old male patient presented with left sided nasal obstruction and recurrent epistaxis for last 2 months. On examination, a polypoid mass was noted in the left nasal cavity. The mass was surgically resected. Paraffin-embedded sections were made and stained with hematoxylin and eosin. Microscopic examination revealed intimate admixture of carcinomatous (adenocarcinoma), sarcomatous (chondrosarcoma), primitive neuroendocrine and teratoid elements (immature squamous elements). These findings clearly suggest the diagnosis of sinonasal teratocarcinosarcoma. Sinonasal teratocarcinosarcoma is highly malignant and locally aggressive. About 60% of the patients do not survive beyond 3 years. Total excision and extensive sampling are necessary to reach the diagnosis. Early diagnosis and management can give a better prognosis. PMID- 27194881 TI - Adjunctive role of dental restorations in personal identification of burnt victims. AB - BACKGROUND: Fire remains one of the major causes of morbidity and mortality throughout the world and identification of a body from the fatal fire remains a daunting task. Several forensic cases involve interpretation of burnt human bodies from airline and automobile accidents, bombings and unlawful cremation. Fire is also involved in homicides, suicides, accidental death, arson and in attempts to destroy forensic evidence in criminal cases. Soft tissue destruction from fire can be so extensive that conventional methods of identification may be impossible. However, teeth survive even high temperatures due to their resistant composition and so, obviously, the restorative material housed in the teeth are even more secure and can yield valuable information in personal identification. AIM: To assess the usefulness of most common restorations in personal identification in burnt cases. MATERIALS AND METHODS: The study was conducted on 40 extracted teeth which were divided into four groups (Group 1 - Unrestored teeth, Group 2 - Amalgam restored, Group 3 - Glass ionomer restored and Group 4 - Composite resin restored teeth. The effect of incineration at 200 degrees C, 400 degrees C, 600 degrees C, 800 degrees C, 1000 degrees C for 15 min at each target temperature followed by subsequent cooling was studied. RESULTS: Amalgam restoration was resistant and intact even at 1000 degrees C, whereas GIC and composite restoration are identifiable till 600 degrees C, the residual cavity preparation leaves a clue for narrowing down the spectrum of identification. PMID- 27194882 TI - Compound composite odontoma. AB - The term odontoma has been used as a descriptor for any tumor of odontogenic origin. It is a growth in which both epithelial and mesenchymal cells exhibits complete differentiation. Odontomas are considered as hamartomas rather than true neoplasm. They are usually discovered on routine radiographic examination. Odontomas, according to the World Health Organization, are classified into complex odontoma and compound odontomas. The present paper reports a case of compound composite odontomas. PMID- 27194883 TI - Fibrosarcoma of maxilla: A rare case report. AB - Fibrosarcoma is a malignant tumor of fibroblasts. At one time, it was considered one of the most common soft tissue sarcomas. However, the diagnosis of fibrosarcoma is made much less frequently today because of the recognition and separate classification of other spindle cell lesions that have similar microscopic features. Of all the fibrosarcomas occurring in humans, only 0.05% occur in the head and neck region. Here, we present a case of 22-year-old female patient with the swelling on the left anterior aspect of the face. Histopathologically, the lesion was diagnosed as fibrosarcoma and immunohistochemically, the lesional cells showed positivity for vimentin. PMID- 27194884 TI - Unusual presentation of squamous cell carcinoma in young female patient: A case report and review of literature. AB - Oral squamous cell carcinoma is the most common "malignant neoplasm" of epithelial origin usually affecting individuals over 50 years of age. It is rare in patients aged <40 years old. This report describes a case of squamous cell carcinoma involving anterior mandibular alveolar region in a 17-year-old female patient, with no history of deleterious habits. This report focuses on etiological factors, diagnosis and prognosis related to the case. PMID- 27194885 TI - Dentinogenic ghost cell tumor. AB - Dentinogenic ghost cell tumor (DGCT) is a rare, odontogenic neoplasm which is considered to be a solid variant of calcifying odontogenic cyst (COC) with locally aggressive behavior. It accounts for only 2-14% of all COCs. To the best of our knowledge, only 88 cases of DGCT have been reported in the literature from 1968 to 2014. Herewith, we report a case of DGCT in a 68-year-old male patient with clinical presentation as a soft tissue growth over alveolar ridge and histopathologically characterized by ameloblastomatous epithelium, abundance of eosinophilic material and ghost cells. PMID- 27194886 TI - Role of inflammation in developmental odontogenic pathosis. AB - Periapical infection in the primary tooth may lead to periapical abscess, granuloma, radicular cyst and even osteomyelitis. The infection in primary teeth can also affect the developing successor teeth leading to hypomineralization, hypoplasia, arrest of tooth development, regional odontodysplasia, delayed eruption etc. The purpose of this article is to report a case of malformed permanent tooth in relation to overlying infected deciduous teeth. The probable role of inflammation in pathogenesis of the present condition is also being discussed. PMID- 27194887 TI - Alveolar rhabdomyosarcoma of maxilla. AB - Rhabdomyosarcoma (RMS), a malignant neoplasm of skeletal muscle origin, is the most common soft tissue sarcoma seen in childhood and adolescence. The most frequent site is the head and neck accounting for 40% of all cases and other involved sites are genitourinary tract, retroperitoneum, and to a lesser extent, the extremities. RMS is relatively uncommon in the oral cavity and the involvement of the jaws is extremely rare. Here, we report a case of 50-year-old female with oral RMS involving maxillary alveolar region with clinical, radiological, histopathological and immunohistochemical findings. PMID- 27194888 TI - Can Testing the Impact of Minimal Hepatic Encephalopathy on Driving Skills be Prolific to Translate Research to Real Life Clinical Medicine? PMID- 27194889 TI - Driving Performance Among Patients with Cirrhosis Who Drove to Their Outpatient Hepatology Clinic Appointments. AB - BACKGROUND: Minimal hepatic encephalopathy (MHE) may adversely affect driving skills. AIMS: To compare the driving performance of cirrhotic patients with and without prior HE as well as controls using a driving stimulator and to correlate psychometric testing with driving performance. METHODS: Adult patients with cirrhosis, who drove to the outpatient clinic for their routine appointments underwent a battery of driving and psychometric tests including number connection tests A & B (NCT-A and NCT-B), digit symbol test (DST) and critical flicker and fusion frequency (CFF) testing. RESULTS: Cirrhotics had significantly higher NCT A (39.3 s vs. 31.2 s, P = 0.006) and DST scores (317 s vs. 245 s, P = 0.012), and lower CFF scores Fusion (33 vs. 36 Hz, P = 0.05), Flicker (35 vs. 42 Hz, P = 0.007) than controls. There was no difference in NCT-A, DST and CFF scores between patients with and without HE. Ten (22%) patients, 7 (27%) with prior HE and 3 (15%) without prior HE, had abnormal NCT-A scores (i.e. >control mean +/- 2SD), and 12% of patients with prior HE had one or more driving test accidents, while controls and patients without prior HE had none. Patients with cirrhosis were more likely to hit pedestrians compared to controls (P = 0.05). There was no correlation between CFF, DST and NCTB scores with driving performance test results. CONCLUSIONS: Unlike previous reports, no significant differences were noted between the patients with and without prior HE on psychometric testing, and on the driving simulator, but driving accidents were seen in only those with previous history of HE. PMID- 27194890 TI - PAI-1 4G-4G, MTHFR 677TT, V Leiden 506Q, and Prothrombin 20210A in Splanchnic Vein Thrombosis: Analysis of Individual Patient Data From Three Prospective Studies. AB - BACKGROUND: There are no univocal opinions on the role of genetic thrombophilia on splanchnic vein thrombosis (SVT). We defined genetic thrombophilia the presence of one of these thrombophilic genetic factors (THRGFs): PAI-1 4G-4G, MTHFR 677TT, V Leiden 506Q, and prothrombin 20210A. OBJECTIVES: To evaluate the frequencies of these THRGFs in SVT patients, we analyzed individual data of 482 Caucasian patients, recruited from 2000 to 2014 in three prospective studies. SVT was defined as the presence of thrombosis of portal (PVT), mesenteric (MVT), splenic (SPVT), cava (CT), and hepatic vein (Budd Chiari syndrome, BCS). Pre hepatic SVT (pre-HSVT) was defined as PVT with or without MVT/SPVT, without BCS. Post-hepatic SVT (post-HSVT) was BCS with or without PVT/MVT/SPVT. METHODS: We compared 350 patients with liver cirrhosis (LC), 47 hepatocellular carcinoma (HCC), 37 myeloproliferative neoplasm (MPN), 38 associated disease (AD), 10 without any associated disease (WAD), vs 150 healthy controls (HC); 437 patients showed pre-HSVT and 45 post-HSVT. RESULTS: Thrombophilia was present in 294/482 (60.9%) patients: 189/350 LC (54.0%), 31/47 (66.0%) HCC, 29/39 (74.4%) MPN, 35/38 AD (92.1%), and 10/10 (100%) WAD, and 54/150 (36.0%) in HC. In the total group, we found 175 PAI-1 4G-4G, 130 MTHFR 677TT, 42V Leiden 506Q, and 27 prothrombin 20210A; 75 patients showed presence of >1 TRHGF; the more frequent association was PAI-1 4G-4G/MTHFR 677TT, in 36 patients. PAI-1 4G-4G and MTHFR 677TT were significantly more frequent in patients with SVT (P values <0.005), whereas V Leiden Q506 and prothrombin G20210A were not. PAI-1 4G-4G and MTHFR 677TT distributions deviated significantly from that expected from a population in Hardy-Weinberg equilibrium. Thrombophilia was significantly less frequent in patients with pre-HSVT (250/437, 57.2%) than in patients with post-HSVT (44/45, 97.8%). CONCLUSIONS: Our study shows the significant prevalence of PAI-1 4G-4G and MTHFR 677TT in SVT, mainly in post-HSVT. PMID- 27194891 TI - Changes in Liver Volume in Patients with Chronic Hepatitis C Undergoing Antiviral Therapy. AB - AIM: Liver volumetric analysis has not been used to detect hepatic remodelling during antiviral therapy before. We measured liver volume (LV) changes on volumetric magnetic resonance imaging during hepatitis C antiviral therapy. METHODS: 22 biopsy-staged patients (median [range] age 45(19-65) years; 9F, 13M) with chronic hepatitis C virus infection were studied. LV was measured at the beginning, end of treatment and 6 months post-treatment using 3D T1-weighted acquisition, normalised to patient weight. Liver outlines were drawn manually on 4 mm thick image slices and LV calculated. Inter-observer agreement was analysed. Patients were also assessed longitudinally using biochemical parameters and liver stiffness using FibroscanTM. RESULTS: Sustained viral response (SVR) was achieved in 13 patients with a mean baseline LV/kg of 0.022 (SD 0.004) L/kg. At the end of treatment, the mean LV/kg was 0.025 (SD 0.004, P = 0.024 cf baseline LV/kg) and 0.026 (SD 0.004, P = 0.008 cf baseline LV/kg) 6 months post-treatment (P = 0.030 cf baseline, P = 0.004). Body weight-corrected end of treatment LV change was significantly higher in patients with SVR compared to patients not attaining SVR (P = 0.050). End of treatment LV change was correlated to initial ALT (R (2) = 0.479, P = 0.037), but not APRI, AST, viral load or liver stiffness measurements. There was a correlation of 0.89 between observers for measured slice thickness. CONCLUSIONS: LV increased during anti-viral treatment, while the body weight corrected LV increase persisted post-antiviral therapy and was larger in patients with SVR. PMID- 27194893 TI - Acute-on-Chronic Liver Failure (ACLF) in Coastal Eastern India: "A Single-Center Experience". AB - BACKGROUND AND OBJECTIVES: Acute-On-Chronic liver failure (ACLF) is an emerging entity. The present study was undertaken to analyze the clinical profile and natural course of ACLF patients. PATIENTS AND METHODS: ACLF was defined as per Asia Pacific Association for the Study of Liver consensus criteria 2009. Patients fulfilling these criteria with some deviations were included and prospectively evaluated for clinical profile, etiologies of acute decompensation (AD) and underlying chronic liver disease, and short-term natural course [3 months]. RESULTS: Out of 123 patients with ACLF (mean age: 45.83 +/- 12.05 years; male:female 109:14), 45.53% cases had prior history of AD, and 54.47% presented for the first time as ACLF. Etiologies of cirrhosis were alcohol, cryptogenic, and chronic hepatitis B virus infection in 65.04%, 23.57%, and 11.38% cases, respectively. Recent history of alcohol intake (within 4 weeks) [42.27%] followed by bacterial infections [36.58%] were the common etiologic precipitants for AD. Only 87 (70.73%) out of 123 cases could be followed up for a duration of 3 months; 62 (71.26%) cases died by 3 months. Most deaths occurred in the alcoholics compared to nonalcoholics [(43/53) 81.13% vs. (19/34) 55.88%; P = 0.01]. No significant difference in mortality rate was observed between ACLF cases with history of prior AD compared to newly diagnosed ACLF cases [30/40 (75%) vs. 32/47 (68.09%); P = 0.477]. The prognostic markers [MELD, MELD-Na, CTP] were not significantly different between survivors and nonsurvivors. CONCLUSION: ACLF patients in our population had high short-term mortality rates with majority of deaths in alcoholics. Alcohol intake and bacterial infections were mainly responsible for AD in our study. PMID- 27194892 TI - Hepatitis C Virus Infection in Patients with End-Stage Renal Disease: A Study from a Tertiary Care Centre in India. AB - BACKGROUND: Hepatitis C Virus (HCV) infection is common in patients with end stage renal disease (ESRD) and is an important cause of liver disease. We describe the demographic, clinical and biochemical profile of these patients from a tertiary care center of north India. METHODS: Records of consecutive patients of HCV infection with ESRD on maintenance hemodialysis or with renal transplantation who presented to our unit from January 2009 to June 2013 were analyzed. The diagnosis of HCV was based on HCV-RNA positivity and/or positive anti-HCV serology. Those with positive anti-HCV serology and negative HCV-RNA on two occasions at 3-month interval, without treatment with interferon, were excluded. RESULTS: 140 patients (median age 44 years [range 18-68], 69% males) were included. Six patients had co-infections (HBV 5, HIV 1). Most (99, 71%) patients were asymptomatic for liver disease and HCV was identified either on routine screening (39, 28%) or during investigation for raised liver enzymes (60, 43%). Remaining 41 (29%) were symptomatic for liver disease, either in the form of jaundice alone (14, 10%), or decompensated liver disease (27, 19%). Median time between initiation of hemodialysis and HCV detection was 33 (range 0-124) months. Thirty-four (27%) patients had received renal transplantation. In 11 patients HCV was detected after renal transplantation. In 23 (18%) patients anti HCV was falsely negative but HCV-RNA was positive. Nearly 35% patients had concomitant diabetes. Median Bilirubin, AST, and ALT were 1.1 mg/dL, 42 IU/L and 44 IU/L, respectively. HCV-RNA was more than 5 log in 49/88(59%) patients. Median HCV-RNA was 6.5 * 10(5) IU/ml (Range 650 to >10 million IU/ml). Genotype-1 was the commonest genotype (30/56, 54%) followed by genotype-3 (17/56, 30%). CONCLUSION: HCV infection is usually asymptomatic in patients with ESRD, however, it may lead to jaundice and decompensated liver disease. False negative anti-HCV is quite common. We found that genotype-1 was commoner than genotype-3 in our cohort of ESRD patients. Most of the patients have high viral load. PMID- 27194894 TI - Multiplex Reverse Transcriptase-PCR for Simultaneous Detection of Hepatitis B, C, and E Virus. AB - INTRODUCTION: The hepatitis B virus (HBV), HCV, and HEV may occur as singly or concurrently in patients of different kind of liver disease. The rapid, reliable, and cost-effective screening of these pathogens is required for the large epidemiological studies. Therefore, a study has been planned to develop a multiplex Reverse Transcriptase-PCR assay which can be used for the screening of maximum number of pathogens at a time. METHODOLOGY: To develop multiplex Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) assay for simultaneous detection of HBV, HCV, and HEV; the serum samples of 54 patients who were positive either singly or in co-infection with for HBV, HCV, and HEV serologically were screened by uniplex PCR/RT-PCR followed by multiplex RT-PCR for HBV, HCV, and HEV using specific primers. These primers can detect most genotypes of these viruses. Multiplex RT-PCR was done in one tube for the identification of viral DNA/RNA using a mixture of three pairs of specific primers for hepatitis B, C, and E viruses. Representative positive samples of these viruses by uniplex/multiplex RT PCR were also confirmed by sequencing followed by alignment with reference strains sequence. RESULTS: The specificity of multiplex PCR was 100% with high sensitivity 89%, 87%, and 74% for HBV, HCV, and HEV respectively. The sensitivity and specificity of RT-multiplex PCR demonstrated a good correlation with that of uniplex PCR. CONCLUSION: The study suggests that multiplex RT-PCR can serve as a simple and reliable assay for rapid, sensitive, and cost-effective method for simultaneous detection of super-infections with HEV particularly in Asian countries as a cause of decompensation of chronic liver disease. PMID- 27194895 TI - Coffee and Liver Disease. AB - Coffee is the most popular beverage in the world. Consumption of coffee has been shown to benefit health in general, and liver health in particular. This article reviews the effects of coffee intake on development and progression of liver disease due to various causes. We also describe the putative mechanisms by which coffee exerts the protective effect. The clinical evidence of benefit of coffee consumption in Hepatitis B and C, as well as nonalcoholic fatty liver disease and alcoholic liver disease, has also been presented. Coffee consumption is associated with improvement in liver enzymes (ALT, AST, and GGTP), especially in individuals with risk for liver disease. Coffee intake more than 2 cups per day in patients with preexisting liver disease has been shown to be associated with lower incidence of fibrosis and cirrhosis, lower hepatocellular carcinoma rates, as well as decreased mortality. PMID- 27194897 TI - "Hockey Stick" may Strike Back: Hepatocellular Carcinoma on Noncirrhotic Liver as a Late Toxicity of Lombo-Aortic Radiotherapy for Seminoma. A Review Triggered by an Unusual Case. AB - Most patients with testicular seminoma have been treated with a curative intent for decades. Second cancers after radiotherapy for testicular seminoma before 1990 are a growing issue, and are related to previous generation of dose planning and delineating strategies. Among those cancers, hepatocellular carcinoma is an extremely rare occurrence, especially when affecting patients with healthy, noncirrhotic liver. Here, we describe such a case in a patient of our institution, and subsequently review the relevant literature and large epidemiologic studies. Understanding those late and serious toxicity features may help cancer care teams to screen and treat those patients appropriately. PMID- 27194898 TI - Dengue Virus Transmission from Living Donor to Recipient in Liver Transplantation: A Case Report. AB - Many infections are transmitted from a donor to a recipient through organ transplantations. The transmission of dengue virus from a donor to a recipient in liver transplantation is a rare entity, and currently, there is no recommendation for screening this virus prior to transplantation. We report a case of transmission of dengue virus from donor to recipient after liver transplantation. The recipient had a history of multiple admissions for hepatic encephalopathy and ascites. He was admitted in the ICU for 15 days for chronic liver disease, ascites, and acute kidney injury before transplantation. The donor was admitted 1 day before transplantation. The donor spiked fever on postoperative day 2 followed by thrombocytopenia and elevated liver enzymes. The donor blood test was positive for dengue NS1 antigen. The recipient also had a similar clinical picture on postoperative day 5 and his blood test was also positive for dengue NS1 antigen. Hence, the diagnosis for posttransplant donor-derived allograft related transmission of dengue infection was made. Both recipient and donor were treated with supportive measures and discharged after their full recovery on postoperative days 9 and 18, respectively. The effect of immunosuppression on dengue presentation is still unclear and there is lack of literature available. In our case, the recipient developed dengue fever similar to general population without showing any feature of severe graft dysfunction. We have concluded that dengue virus can also be transmitted from donor to recipient, and immunosuppression did not have any adverse effect on the evolution of dengue fever within the recipient. Delhi being a hyperendemic zone, screening for donors (especially in season time) for dengue virus seems to be the best preventive method to control donor-derived transmission of dengue to recipient. PMID- 27194896 TI - Liver Transplantation for Alcohol-Related Liver Disease. AB - Alcoholic liver disease (ALD) is a common indication for liver transplantation. It is a much debated indication for deceased donor liver transplantation due to organ shortage and potential of alcohol relapse after liver transplantation. A six-month abstinence before liver transplantation is required at most centers to decrease chances of alcohol relapse after liver transplantation. However, this rule is not relevant for patients with severe alcoholic hepatitis or severely decompensated patients who are unlikely to survive till 6 months. Long-term care of these patients after liver transplantation includes assessment of relapse, smoking, and surveillance of de novo malignancies. Current review discusses role of abstinence, factors affecting alcohol relapse, liver transplantation for alcoholic hepatitis, role of living donor liver transplantation, and long-term care of ALD patients who undergo liver transplantation. PMID- 27194899 TI - Pyoderma Gangrenosum-A New Manifestation of Wilson Disease? AB - Seventeen year old girl, a known case of Wilson disease presented to us with a non-healing skin ulcer followed by appearance of jaundice, ascites and progressive fatigue of 1 month duration. She was diagnosed to have Wilson disease 5 years back and had been well controlled on d-penicillamine. On enquiry, she was found to be noncompliant with her medication in the preceding 6 months. On examination, she had severe pallor, icterus with moderate ascites and oedema feet. Investigations revealed severe haemolytic anemia and deranged liver function. The lesion was diagnosed to be pyoderma gangrenosum on skin biopsy. The appearance of a cutaneous lesion followed by deterioration in the liver disease and hemolysis suggested uncontrolled Wilson disease as the triggering factor. Chelation therapy improved her haemoglobin and liver function as well as led to healing of the ulcer. We describe pyoderma gangrenosum as a new manifestation of Wilson disease. PMID- 27194900 TI - A Rare Congenital Disorder of Intrahepatic Bile Ducts. PMID- 27194901 TI - Advances in Management of Hepatocellular Carcinoma. PMID- 27194903 TI - Variceal Banding: A Lesser-Known Complication. PMID- 27194902 TI - Hepatobiliary Quiz Answers-17 (2016). PMID- 27194904 TI - Risk factors for visual impairment associated with corneal diseases in southern China. AB - PURPOSE: To identify the most common etiologies of corneal disease and the risk factors associated with worse visual outcomes in Changsha, Hunan, located in southern China. METHODS: This observational, cross-sectional study evaluated 100 consecutive patients seen at the cornea clinic of The Second Xiangya Hospital of Central South University. Ocular history, demographic information, and ocular use of traditional Chinese medicine were recorded and analyzed. Causes of infectious keratitis were diagnosed clinically. Fungal and acanthamoeba keratitis were confirmed by confocal microscopy. Visual impairment was categorized based on visual acuity according to World Health Organization recommendations. A binary logistic regression model was used to calculate odds ratio (OR). RESULTS: One hundred consecutive patients were evaluated. Sixty patients (60%) had noninfectious corneal diseases, most commonly dry eye syndrome (26.7%, n=16), followed by corneal abrasion (18.3%, n=11). Forty-five patients had infectious keratitis, five of whom had both infectious and noninfectious etiologies. Of the patients with infectious keratitis, viral keratitis was the most frequent cause (57.8%, n=26), followed by fungal (20%, n=9) and bacterial (20%, n=9). Older age (OR =5.08, P=0.048), male sex (OR =3.37, P=0.035), and rural residence (OR =3.11, P=0.017) had increased odds of having worse visual impairment. Rural residence was also associated with infectious keratitis (P=0.005), particularly bacterial and fungal keratitis (P=0.046), and a history of ocular trauma (P=0.003). Occupation was not a significant risk factor in this population. Fourteen patients reported use of traditional Chinese medicine, with no association with visual outcomes found. CONCLUSION: Older age, male sex, and rural residence were associated with worse visual impairment. Prevalence and outcome of corneal diseases may be improved with an increased awareness in these populations. PMID- 27194905 TI - Pharmacokinetics and aqueous humor penetration of levofloxacin 1.5% and moxifloxacin 0.5% in patients undergoing cataract surgery. AB - PURPOSE: The objective of this study was to compare the pharmacokinetics of levofloxacin 1.5% and moxifloxacin hydrochloride 0.5% ophthalmic solutions in aqueous humor after multiple doses prior to cataract surgery. METHODS: Ninety eight eyes underwent cataract surgery and met the requirements of PK analysis. Eligible eyes were randomly assigned in a 1:1 ratio to receive levofloxacin or moxifloxacin prior to cataract surgery and were randomized into one of four sampling time points (ie, 1, 2, 4, and 6 hour post-last dose). Randomization was investigator and laboratory-masked. Three days prior to cataract surgery, each patient instilled one drop of the assigned study medication into the operative eye four times daily. One aqueous humor specimen was collected from the eye at the randomized time point. Aqueous humor specimens were assayed for drug concentration using a validated liquid chromatography and tandem mass spectrometer. RESULTS: Concentrations of the drug in the aqueous humor, as described by mean Cmax and pooled AUC0-6 values, were greater for levofloxacin than moxifloxacin (Cmax: 1.43, 0.87 MUg/ml, respectively, P=0.008; AUC0-6 6.1, 3.8 MUg.min/ml, P<0.001 respectively). No treatment-emergent adverse events were reported. CONCLUSION: Significantly greater drug exposures were attained in aqueous humor following the administration of levofloxacin 1.5% than moxifloxacin 0.5% ophthalmic solution. Achieving considerable higher drug concentration in the aqueous humor with levofloxacin 1.5% may demonstrate a greater potential for bacterial eradication. PMID- 27194906 TI - Hospitalization in older patients due to adverse drug reactions -the need for a prediction tool. AB - Adverse drug reactions (ADRs) represent a major burden on society, resulting in significant morbidity, mortality, and health care costs. Older patients living in the community are particularly susceptible to ADRs, and are at an increased risk of ADR-related hospitalization. This review summarizes the available evidence on ADR-related hospital admission in older patients living in the community, with a particular focus on risk factors for ADRs leading to hospital admission and the need for a prediction tool for risk of ADR-related hospitalization in these individuals. The reported proportion of hospital admissions due to ADRs has ranged from 6% to 12% of all admissions in older patients. The main risk factors or predictors for ADR-related admissions were advanced age, polypharmacy, comorbidity, and potentially inappropriate medications. There is a clear need to design intervention strategies to prevent ADR-related hospitalization in older patients. To ensure the cost-effectiveness of such strategies, it would be necessary to target them to those older individuals who are at highest risk of ADR-related hospitalization. Currently, there are no validated tools to assess the risk of ADRs in primary care. There is a clear need to investigate the utility of tools to identify high-risk patients to target appropriate interventions toward prevention of ADR-related hospital admissions. PMID- 27194907 TI - Validity and reliability of the Persian version of the Brief Aging Perceptions Questionnaire in Iranian older adults. AB - BACKGROUND: Perceptions of aging refer to individuals' understanding of aging within their sociocultural context. Proper measurement of this concept in various societies requires accurate tools. OBJECTIVE: The present study was conducted with the aim to translate and validate the Brief Aging Perceptions Questionnaire (B-APQ) and assess its psychometric features in Iranian older adults. METHOD: In this study, the Persian version of B-APQ was validated for 400 older adults. This questionnaire was translated into Persian according to the Wild et al's model. The Persian version was validated using content, face, and construct (using confirmatory factor analysis) validities, and then its internal consistency and test-retest reliability were measured. Data were analyzed using the statistical software programs SPSS 18 and EQS-6.1. RESULTS: The confirmatory factor analysis confirmed construct validity and five subscales of B-APQ. Test-retest reliability with 3-week interval produced r=0.94. Cronbach's alpha was found to be 0.75 for the whole questionnaire, and from 0.53 to 0.77 for the five factors. CONCLUSION: The Persian version of B-APQ showed favorable validity and reliability, and thus it can be used for measuring different dimensions of perceptions of aging in Iranian older adults. PMID- 27194908 TI - Vital capacity and COPD: the Swedish CArdioPulmonary bioImage Study (SCAPIS). AB - BACKGROUND: Spirometric diagnosis of chronic obstructive pulmonary disease (COPD) is based on the ratio of forced expiratory volume in 1 second (FEV1)/vital capacity (VC), either as a fixed value <0.7 or below the lower limit of normal (LLN). Forced vital capacity (FVC) is a proxy for VC. The first aim was to compare the use of FVC and VC, assessed as the highest value of FVC or slow vital capacity (SVC), when assessing the FEV1/VC ratio in a general population setting. The second aim was to evaluate the characteristics of subjects with COPD who obtained a higher SVC than FVC. METHODS: Subjects (n=1,050) aged 50-64 years were investigated with FEV1, FVC, and SVC after bronchodilation. Global Initiative for Chronic Obstructive Lung Disease (GOLD) COPDFVC was defined as FEV1/FVC <0.7, GOLDCOPDVC as FEV1/VC <0.7 using the maximum value of FVC or SVC, LLNCOPDFVC as FEV1/FVC below the LLN, and LLNCOPDVC as FEV1/VC below the LLN using the maximum value of FVC or SVC. RESULTS: Prevalence of GOLDCOPDFVC was 10.0% (95% confidence interval [CI] 8.2-12.0) and the prevalence of LLNCOPDFVC was 9.5% (95% CI 7.8 11.4). When estimates were based on VC, the prevalence became higher; 16.4% (95% CI 14.3-18.9) and 15.6% (95% CI 13.5-17.9) for GOLDCOPDVC and LLNCOPDVC, respectively. The group of additional subjects classified as having COPD based on VC, had lower FEV1, more wheeze and higher residual volume compared to subjects without any COPD. CONCLUSION: The prevalence of COPD was significantly higher when the ratio FEV1/VC was calculated using the highest value of SVC or FVC compared with using FVC only. Subjects classified as having COPD when using the VC concept were more obstructive and with indications of air trapping. Hence, the use of only FVC when assessing airflow limitation may result in a considerable under diagnosis of subjects with mild COPD. PMID- 27194909 TI - Voltammetric determination of melatonin using a graphene-based sensor in pharmaceutical products. AB - Melatonin can be sensitively detected in pharmaceuticals by cyclic voltammetry and fixed-potential amperometry using a graphene-based sensor. The sensor characterization of cyclic voltammetry constantly provides high values of electrode active area and heterogeneous rate constant. In optimal conditions, the sensor was applied for the determination of melatonin in different pharmaceutical samples. The sensitivity to melatonin was 0.0371 A M(-1), and the limit of detection was 0.87*10(-6) M. The data obtained by using the graphene-based sensor for the detection of melatonin in pharmaceutical products were in good agreement with the data provided by the producer. Since no interferences from the excipients were found, using a separation technique was not necessary. Additionally, the low price, ease of handling, small amount of sample, short time per analysis, and possibility of automation are the important advantages that recommend this methodology for quality control of pharmaceuticals. PMID- 27194911 TI - Psychological and behavioral intervention improves the quality of life and mental health of patients suffering from differentiated thyroid cancer treated with postoperative radioactive iodine-131. AB - BACKGROUND: We examined the effects of psychological and behavioral intervention on health-related quality of life and mental health among patients suffering from differentiated thyroid cancer (DTC) treated with postoperative radioactive iodine 131 (RAI). METHODS: Sixty patients with DTC, undergoing RAI, were randomly assigned to receive either conventional nursing (n=30) or a 1-year psychological and behavioral intervention based on conventional nursing (n=30). Health-related quality of life and mental health issues, depression, and anxiety were measured using the Quality of Life Core Questionnaire, Self-rating Depression Scale, and Self-rating Anxiety Score, respectively. RESULTS: After RAI treatment, patients in both groups showed improved functional capacities (ie, physical, role, cognitive, emotional, and social) and global quality of life, along with reduced depression and anxiety (P<0.05). At 1-year follow-up, compared with patients in the routine nursing group, those in the psychological and behavioral intervention group demonstrated greater improvements in functional capacities, global quality of life, and depression and anxiety symptoms (P<0.05). CONCLUSION: Psychological and behavioral interventions for patients with DTC undergoing RAI facilitated positive outcomes, suggesting that nursing care models that include psychological and behavioral interventions may be a complementary strategy for this patient population. PMID- 27194910 TI - Enhancing the in vivo transdermal delivery of gold nanoparticles using poly(ethylene glycol) and its oleylamine conjugate. AB - In this study, we investigated the effect of (ethylene glycol) (PEG) and PEG oleylamine (OAm) functionalization on the skin permeation property of gold nanoparticles (GNS) in vivo. Chemisorption of polymers onto GNS was verified by a red shift in the ultraviolet-visible spectrum as well as by a change in the nanoparticle surface charge. The physicochemical properties of pristine and functionalized nanoparticles were analyzed by ultraviolet-visible spectroscopy, zeta potential analyzer, and transmission electron microscopy. Transmission electron microscopy revealed that the interparticle distance between nanoparticles increased after GNS functionalization. Comparing the skin permeation profile of pristine and functionalized GNS, the follicular deposition of GNS increased twofold after PEG-OAm functionalization. Moreover, PEG- and PEG OAm-functionalized nanoparticles were able to overcome the skin barrier and deposit in the deeper subcutaneous adipose tissue. These findings demonstrate the potential of PEG- and PEG-OAm-functionalized GNS in serving a multitude of applications in transdermal pharmaceuticals. PMID- 27194912 TI - High-intensity focused ultrasound therapy in combination with gemcitabine for unresectable pancreatic carcinoma. AB - OBJECTIVE: To investigate the therapeutic effect and safety of high-intensity focused ultrasound (HIFU) therapy combined with gemcitabine in treating unresectable pancreatic carcinoma. METHODS: The 45 patients suffering from pancreatic carcinoma were randomized into two groups. The patients in the experimental group (n=23) received HIFU in combination with gemcitabine and those in the control group (n=22) received gemcitabine alone. The effect and clinical benefit rates in the two groups were compared. The median survival time and 6 month and 12-month survival rates were calculated by Kaplan-Meier method and log rank test. RESULTS: The median survival time and 6-month survival rate were significantly higher in the experimental group than in the control group (8.91 months vs 5.53 months, 73.9% vs 40.9%, respectively P<0.05), but 12-month survival rate was not statistically different between the two groups (13.0% vs 4.5%, P>0.05). The clinical benefit rates in the experimental group and the control group were 69.6% and 36.3%, respectively (P<0.05). The pain remission rate in the experimental group was significantly higher than that in the control group (65.2% vs 31.8%, P<0.05). CONCLUSION: HIFU in combination with gemcitabine is better than gemcitabine alone. This combinatorial therapy may become a better and effective treatment for unresectable pancreatic carcinoma. PMID- 27194913 TI - Management of acute and delayed chemotherapy-induced nausea and vomiting: role of netupitant-palonosetron combination. AB - PURPOSE: The purpose of this review is to summarize and discuss the recently published data (both original studies and reviews) on the oral medication NEPA, consisting of netupitant (a neurokinin-1 receptor antagonist [NK1RA], 300 mg dose) and palonosetron (5-hydroxytryptamine [serotonin or 5HT] type 3 receptor antagonist [5HT3RA], 0.5 mg dose), in the prevention of the acute and delayed nausea and vomiting in patients receiving highly or moderately emetogenic chemotherapy. METHODS: This review was based on the very limited number of available published trials consisting of two Phase III studies and one Phase II dose-selecting trial. RESULTS: These studies demonstrated some therapeutic benefits of NEPA over related chemotherapy-induced nausea and vomiting (CINV) prophylaxis management, as well as its beneficial safety profile. In particular, compared with single-dose 0.5 mg palonosetron, the complete response rates for all phases of CINV for the first cycle of highly emetogenic chemotherapy (with cisplatin), as well as anthracycline-cyclophosphamide-based moderately emetogenic chemotherapy, were significantly higher for single-dose NEPA. The high efficacy of NEPA in terms of prevention of CINV continued throughout repeated cycles of highly and moderately emetogenic therapies. CONCLUSION: It is currently recommended that patients who are administered highly emetogenic chemotherapy regimens should obtain a three-drug combination consisting of NK1RA, 5HT3RA, and dexamethasone. The recently available oral combination of NEPA plus dexamethasone provides an additional pharmacological management option that could be considered in this scenario. PMID- 27194916 TI - Medical student perspective: reducing patient waiting times in the UK National Health Service. PMID- 27194915 TI - Improving nurse-physician teamwork through interprofessional bedside rounding. AB - BACKGROUND: Teamwork between physicians and nurses has a positive association with patient satisfaction and outcomes, but perceptions of physician-nurse teamwork are often suboptimal. OBJECTIVE: To improve nurse-physician teamwork in a general medicine inpatient teaching unit by increasing face-to-face communication through interprofessional bedside rounds. INTERVENTION: From July 2013 through October 2013, physicians (attendings and residents) and nurses from four general medicine teams in a single nursing unit participated in bedside rounding, which involved the inclusion of nurses in morning rounds with the medicine teams at the patients' bedside. Based on stakeholder analysis and feedback, a checklist for key patient care issues was created and utilized during bedside rounds. ASSESSMENT: To assess the effect of bedside rounding on nurse physician teamwork, a survey of selected items from the Safety Attitudes Questionnaire (SAQ) was administered to participants before and after the implementation of bedside rounds. The number of pages to the general medicine teams was also measured as a marker of physician-nurse communication. RESULTS: Participation rate in bedside rounds across the four medicine teams was 58%. SAQ response rates for attendings, residents, and nurses were 36/36 (100%), 73/73 (100%), and 32/73 (44%) prior to implementation of bedside rounding and 36 attendings (100%), 72 residents (100%), and 14 (19%) nurses after the implementation of bedside rounding, respectively. Prior to bedside rounding, nurses provided lower teamwork ratings (percent agree) than residents and attendings on all SAQ items; but after the intervention, the difference remained significant only on SAQ item 2 ("In this clinical area, it is not difficult to speak up if I perceive a problem with patient care", 64% for nurses vs 79% for residents vs 94% for attendings, P=0.02). Also, resident responses improved on SAQ item 1 ("Nurse input is well received in this area", 62% vs 82%, P=0.01). CONCLUSION: Increasing face-to-face communication through interprofessional bedside rounding can improve the perceptions of nurse-physician teamwork, particularly among residents and nurses. PMID- 27194914 TI - Diagnosis and screening of patients with hereditary angioedema in primary care. AB - Hereditary angioedema (HAE) is a rare autosomal dominant disease that commonly manifests with episodes of cutaneous or submucosal angioedema and intense abdominal pain. The condition usually presents due to a deficiency of C1 esterase inhibitor (C1-INH) that leads to the overproduction of bradykinin, causing an abrupt increase in vascular permeability. A less-understood and less-common form of the disease presents with normal C1-INH levels. Symptoms of angioedema may be confused initially with mast cell-mediated angioedema, such as allergic reactions, and may perplex physicians when epinephrine, antihistamine, or glucocorticoid therapies do not provide relief. Similarly, abdominal attacks may lead to unnecessary surgeries or opiate dependence. All affected individuals are at risk for a life-threatening episode of laryngeal angioedema, which continues to be a source of fatalities due to asphyxiation. Unfortunately, the diagnosis is delayed on average by almost a decade due to a misunderstanding of symptoms and general lack of awareness of the disease. Once physicians suspect HAE, however, diagnostic methods are reliable and available at most laboratories, and include testing for C4, C1-INH protein, and C1-INH functional levels. In patients with HAE, management consists of acute treatment of an attack as well as possible short- or long-term prophylaxis. Plasma-derived C1-INH, ecallantide, icatibant, and recombinant human C1-INH are new treatments that have been shown to be safe and effective in the treatment of HAE attacks. The current understanding of HAE has greatly improved in recent decades, leading to growing awareness, new treatments, improved management strategies, and better outcomes for patients. PMID- 27194918 TI - Partial-thickness corneal tissue restoration after a chemical burn. AB - PURPOSE: We describe a case of full-thickness corneal restoration after an acute corneal burn with an acid agent. METHODS: A 32-year-old male reported painful discomfort, redness, photophobia, and a decrease in visual acuity in the left eye after a unilateral burn with an acid agent. Slit-lamp examination revealed massive corneal melting involving necrotic sequestrum of the entire corneal surface. Surgical approach was carried out in order to preserve residual ocular tissues. RESULTS: Extensive corneal-conjunctival layer curettage of the necrotic tissue was performed showing perfectly clear undamaged deep lamellar corneal layers. The patient underwent multilayered amniotic membrane transplantation and total capsular-conjunctival flap in order to preserve ocular tissue from further melting or corneal perforation. A complete and spontaneous "restitutio ad integrum" of the corneal layers was shown during the follow-up. The cornea was perfectly clear with restored normal anatomical architecture. CONCLUSION: In this case, a spontaneous full-thickness corneal tissue restoration occurred after an acute chemical burn. Studies about the mechanisms whereby different cells interact and replicate within the stroma may unveil the biology behind corneal regeneration and transparency. PMID- 27194917 TI - Genetics of Lafora progressive myoclonic epilepsy: current perspectives. AB - Lafora disease (LD) is a fatal neurodegenerative disorder caused by loss-of function mutations in either laforin glycogen phosphatase gene (EPM2A) or malin E3 ubiquitin ligase gene (NHLRC1). LD is associated with gradual accumulation of Lafora bodies (LBs). LBs are aggregates of polyglucosan, a long, linear, poorly branched, hyperphosphorylated, insoluble form of glycogen. Loss-of-function mutations either in the EPM2A or in the NHLRC1 gene lead to polyglucosan formation. One hypothesis on LB formation is based on findings that laforin-malin complex downregulates glycogen synthase (GS) through malin-mediated ubiquitination, and the other one is based on findings that laforin dephosphorylates glycogen. According to the first hypothesis, polyglucosan formation is a result of increased GS activity, and according to the second, an increased glycogen phosphate leads to glycogen conformational change, unfolding, precipitation, and conversion to polyglucosan, while GS remains bound to the precipitating glycogen. In this review, we summarize all the recent findings that have important implications for the treatment of LD, all of them showing that partial inhibition of GS activity may be sufficient to prevent the progression of the disease. The current perspective in LD is high-throughput screening for small molecules that act on the disease pathway, that is, partial inhibitors of GS, which opens a therapeutic window for potential treatment of this fatal disease. PMID- 27194919 TI - Lasers in tattoo and pigmentation control: role of the PicoSure((r)) laser system. AB - BACKGROUND AND OBJECTIVES: The use of picosecond lasers to remove tattoos has greatly improved due to the long-standing outcomes of nanosecond lasers, both clinically and histologically. The first aesthetic picosecond laser available for this use was the PicoSure((r)) laser system (755/532 nm). Now that a vast amount of research on its use has been conducted, we performed a comprehensive review of the literature to validate the continued application of the PicoSure((r)) laser system for tattoo removal. STUDY DESIGN AND METHODS: A PubMed search was conducted using the term "picosecond" combined with "laser", "dermatology", and "laser tattoo removal". RESULTS: A total of 13 articles were identified, and ten of these met the inclusion criteria for this review. The majority of studies showed that picosecond lasers are an effective and safe treatment mode for the removal of tattoo pigments. Several studies also indicated potential novel applications of picosecond lasers in the removal of various tattoo pigments (eg, black, red, and yellow). Adverse effects were generally mild, such as transient hypopigmentation or blister formation, and were rarely more serious, such as scarring and/or textural change. CONCLUSION: Advancements in laser technologies and their application in cutaneous medicine have revolutionized the field of laser surgery. Computational modeling provides evidence that the optimal pulse durations for tattoo ink removal are in the picosecond domain. It is recommended that the PicoSure((r)) laser system continue to be used for safe and effective tattoo removal, including for red and yellow pigments. PMID- 27194920 TI - An Overview of Meat Industry in Sri Lanka: A Comprehensive Review. AB - Livestock is considered as one of the most important segments in agriculture since animal husbandry was practiced for centuries as a backyard system by rural families. Livestock plays as a powerful tool in rural development where meat industry contributes a dominant part. Meat and meat products become a vital component in the diet, which had been one of the main protein sources traditionally as well. The development in the livestock and meat industry of Sri Lanka basically depends upon religious, cultural, and economic factors. There is a growing demand for processed meat products in Sri Lankan urban culture and several large scale processors entered the business during the past few decades. The consumption of meat and meat products shows an upward trend in Sri Lanka during the last decade and is anticipated to increase further in future. The growth potential of the local meat industry is considerably high owing to the improvement of the market and consumer perception. The present status, trends, and future prospects for the Sri Lankan meat industry with respect to production, consumption, processing, marketing, and improvement are discussed in this review. PMID- 27194921 TI - The Relationship between Chemical Compositions, Meat Quality, and Palatability of the 10 Primal Cuts from Hanwoo Steer. AB - The relationship between chemical compositions, meat quality traits, and palatability attributes in 10 primal cuts from Hanwoo steer carcasses were assessed. Sensory palatability attributes of Hanwoo beef were more closely related with fat content than to moisture or protein content. Among the chemical compositions, only fat had a significant correlation with juiciness (0.67, p<0.001), tenderness (0.32, p<0.05), and overall palatability (0.56, p<0.001). Oleic acid (%) was not significantly related with overall palatability (p>0.05). Overall palatability was negatively correlated with drip loss (-0.32, p<0.05), cooking loss (-0.36, p<0.05), and shear force (-0.54, p<0.01). The correlation between fat content and overall palatability was increased when higher fat cuts (Ansim, Dungsim, Chaekeut, Yangjee, and Kalbi) were analyzed, compared to lower fat cuts (Moksim, Abdari, Udun, Suldo, and Satae). Also, the correlation between shear force and overall palatability was decreased in lower fat cuts compared to higher fat cuts. Our results suggest that the palatability of Hanwoo beef can be improved by increasing fat content in muscles, as increased fat content leads to an increase in sensory tenderness, flavor, and juiciness. PMID- 27194922 TI - Effects of Various Salts on Physicochemical Properties and Sensory Characteristics of Cured Meat. AB - This study was carried out to investigate the effects of refined, solar, and bamboo salt on the physico-chemical properties and sensory characteristics of cured pork loin. Moisture, protein, fat, and ash content, lightness, yellowness, cooking yield, and color, juiciness, and tenderness of sensory properties on curing pork loin exhibited no significant differences regardless of the nature of salts. The pH of raw and cooked cured pork loin with added bamboo salt was higher that of other salt treatments. However, the cooking loss, and Warner-Bratzler shear force of cured pork loin with added refined salt was lower than those of solar and bamboo salt pork loins cured. The flavor and overall acceptability scores of treatments with refined salt was higher than those of solar and bamboo salt treatments. The unique flavor of bamboo salt can render it as a functional material for marinating meat products. In addition, the results of this study reveal potential use of bamboo salt in meat curing. PMID- 27194923 TI - Postmortem Aging of Beef with a Special Reference to the Dry Aging. AB - Animal muscles are stored for specific period (aging) at refrigerated temperatures, during and after which the living muscles start to convert into meat and thus, attain certain superior properties in the final product. Proteolysis, lipolysis, and oxidation are the major biochemical processes involved during the postmortem aging of meat that affect the tenderness, juiciness, and flavor, as well as sometimes may introduce certain undesirable traits. This review analyzes the role of pre- and post-mortem factors that are important for aging and their effect on the chemical and physical changes in the "dry- and wet-aged meat." Thus, if the meat processing manufacturers optimize the effects of aging for specific muscles, the palatability, color, and the shelf life of the aged meat products could be significantly enhanced. PMID- 27194924 TI - Anti-diabetic Effect of Fermented Milk Containing Conjugated Linoleic Acid on Type II Diabetes Mellitus. AB - Conjugated linoleic acid (CLA) is a group of positional and geometric isomers of conjugated dienoic derivatives of linoleic acid. CLA has been reported to be able to reduce body fat. In this study, we investigated the antidiabetic effect of fermented milk (FM) containing CLA on type II diabetes db/db mice. Mice were treated with 0.2% low FM, 0.6% high FM, or Glimepiride (GLM) for 6 wk. Our results revealed that the body weight and the levels of fasting blood glucose, serum insulin, and leptin were significantly decreased in FM fed mice compared to db/db mice. Oral glucose tolerance and insulin tolerance were significantly ameliorated in FM fed mice compared to db/db mice. Consistent with these results, the concentrations of serum total cholesterol, triglycerides, and LDL cholesterol were also significantly decreased in FM fed mice compared to db/db mice. However, the concentration of HDL cholesterol was significantly higher in FM fed mice compared to db/db mice. These results were similar to those of GLM, a commercial anti-diabetic drug. Therefore, our results suggest that FM has anti-diabetic effect as a functional food to treat type II diabetes mellitus. PMID- 27194925 TI - Effect of Different Cooking Methods on the Composition of Intramuscular Fatty Acids of Hyla Rabbit. AB - The influence of three cooking methods (stewing, microwaving and Aluminium (Al) foil-baking) was evaluated on the content of intramuscular lipid and the composition of intramuscular fatty acids of Hyla rabbit. The percentage of intramuscular lipid in cooked-longissimus dorsi (LD) (dry weight %) were in the order mentioned below: microwaving > foil-baking > stewing. All treated samples showed decrease in the proportion of polyunsaturated fatty acids (PUFA) and monounsaturated fatty acids (MUFA), whilst increase in the proportion of saturated (SFA) and n-6/n-3 value during processing. All of the cooked samples had the n-6/n-3 ratio within the recommended range (5-10). By the analysis of partial least squares regression (PLSR), the microwaving treatment was better to keep the stability of unsaturated fatty acids (UFA), whilst the long-time Al foil baking did the most serious damage to UFA, especially the PUFA. In addition, the heating method showed greater influence on the samples than the processing time. The shorter processing time was better to retain the intramuscular PUFA of Hyla rabbit, especially the LC-PUFAs (C20-22). Considering all the factors, microwaving showed the superiority in reserving the composition of intramuscular fatty acids of Hyla rabbit. PMID- 27194926 TI - Inhibiting the Growth of Escherichia coli O157:H7 in Beef, Pork, and Chicken Meat using a Bacteriophage. AB - This study aimed to inhibit Escherichia coli (E. coli) O157:H7 artificially contaminated in fresh meat using bacteriophage. Among 14 bacteriophages, the highly lytic bacteriophage BPECO19 strain was selected to inhibit E. coli O157:H7 in artificially contaminated meat samples. Bacteriophage BPECO19 significantly reduced E. coli O157:H7 bacterial load in vitro in a multiplicity of infection (MOI)-dependent manner. E. coli O157:H7 was completely inhibited only in 10 min in vitro by the treatment of 10,000 MOI BPECO19. The treatment of BPECO19 at 100,000 MOI completely reduced 5 Log CFU/cm(2) E. coli O157:H7 bacterial load in beef and pork at 4 and 8h, respectively. In chicken meat, a 4.65 log reduction of E. coli O157:H7 was observed at 4 h by 100,000 MOI. The treatment of single bacteriophage BPECO19 was an effective method to control E. coli O157:H7 in meat samples. PMID- 27194927 TI - Establishing Quantitative Standards for Residual Alkaline Phosphatase in Pasteurized Milk. AB - The alkaline phosphatase (ALP) assay is a rapid and convenient method for verifying milk pasteurization. Since colorimetric ALP assays rely on subjective visual assessments, their results are especially unreliable near the detection limits. In this study, we attempted to establish quantitative criteria for residual ALP in milk by using a more objective method based on spectrophotometric measurements. Raw milk was heat-treated for 0, 10, 20, 30, and 40 min and then subjected to ALP assays. The quantitative criteria for residual ALP in the milk was determined as 2 MUg phenol/mL of milk, which is just above the ALP value of milk samples heat-treated for 30 min. These newly proposed methodology and criteria could facilitate the microbiological quality control of milk. PMID- 27194928 TI - Supplementation of Pork Patties with Bovine Plasma Protein Hydrolysates Augments Antioxidant Properties and Improves Quality. AB - This study investigated the effects of bovine plasma protein (PP) hydrolysates on the antioxidant and quality properties of pork patties during storage. Pork patties were divided into 4 groups: without butylated hydroxytoluene (BHT) and PP hydrolysates (control), 0.02% BHT (T1), 1% PP hydrolysates (T2), and 2% PP hydrolysates (T3). Pork patty supplemented with PP hydrolysates had higher pH values and lower weight loss during cooking than the control patties. Results showed that lightness and hardness both decreased upon the addition of PP hydrolysates. All samples containing BHT and PP hydrolysates had reduced TBARS and peroxide values during storage. In particular, 2% PP hydrolysates were more effective in delaying lipid oxidation than were the other treatments. It was concluded that treatment with 2% PP hydrolysates can enhance the acceptance of pork patty. PMID- 27194929 TI - Detection for Non-Milk Fat in Dairy Product by Gas Chromatography. AB - The aim of this study was to evaluate the potential use of fatty acids, triacylglycerols, and cholesterol in the detection of adulterated milk fat. The fatty acid, triacylglycerol, and cholesterol profiles of the mixtures of milk and non-milk fat (adulteration ratios of 10%, 30%, 50%, 70%, and 90%) were analyzed by gas chromatography. The results showed that concentrations of the fatty acids with oleic acid (C18:1n9c) and linoleic acid (C18:2n6c), triglycerides with C52 and C54, and cholesterol detected are proportional to the adulteration ratios remarkably. Oleic acid (C18:1n9c), linoleic acid (C18:2n6c), C52, and C54 were lower in pure milk fat than in adulterated mixtures. In contrast, pure milk has a higher cholesterol concentration than all adulterated mixtures (adulteration concentration in the range 10-90%). Thus, we suggest that oleic acid (C18:1n9c), linoleic acid (C18:2n6c), C52, C54, and cholesterol are suitable indicators and can be used as biomarkers to rapidly detect adulterated milk fat by gas chromatography. This study is expected to provide basic data for adulteration and material usage. Moreover, this new approach can detect the presence of foreign oils and fats in the milk fat of cheese and can find application in related studies. PMID- 27194930 TI - Application of Electron-Beam Irradiation Combined with Aging for Improvement of Microbiological and Physicochemical Quality of Beef Loin. AB - The combined effects of irradiation and aging temperature on the microbial and chemical quality of beef loin were investigated. The samples were vacuum packaged, irradiated at 0 or 2 kGy using electron-beam (EB), and stored for 10 d at different aging temperatures (2, 14, or 25C). The microbial growth, shear values, meat color, and nucleotide-related flavor compounds of the samples were analyzed. The irradiation effect on inactivation of foodborne pathogens was also investigated. The population of Listeria monocytogenes and Escherhia coli O157:H7 inoculated in beef samples decreased in proportion to the irradiation dose. Irradiation reduced the total aerobic bacteria (TAB) over the storage, but higher aging temperature increased the TBA. Thus TAB increased sharply in non-irradiated and high temperature-aged (14, 25C) beef samples after 5 d. With increasing aging temperature and aging time, shear force values decreased. Lipid oxidation could be reduced by short aging time at low aging temperature. The color a* values of the irradiated beef were lower than those of the non-irradiated throughout the aging period. As aging period and temperature increased, IMP decreased and hypoxanthine increased. Considering microbial and physicochemical properties, irradiation can be used for raw beef to be aged at relatively high temperature to shorten aging time and cost. PMID- 27194931 TI - The Breed and Sex Effect on the Carcass Size Performance and Meat Quality of Yak in Different Muscles. AB - The carcass size performances and the meat quality of Gannan and Sibu yak were determined using M. supraspinatus (SU), M. longissimus thoracis (LT) and M.quadriceps femoris (QF). It is found that Sibu yak had significantly higher carcass weight (CW) than Gannan yak with difference of nearly 40 kg, as well as significantly higher eye muscle area (EMA), carcass thorax depth (CTD), round perimeter (RP), etc. The carcass performances of steer yak were significantly higher than heifer yak except meat thickness at round (MTR) (p<0.05). The results show that both yak breed and gender had significant effects on carcass performances. It could be seen that the variation of carcass size performances from breeds is as large as from gender (50.22% and 46.25% of total variation, respectively) through principal component analysis (PCA). Sibu yak had significantly higher L*, b*, WBSF, cooking loss and Fat content, while Gannan yak had significantly higher a*, press loss, protein content and moisture (p<0.05). Yak gender and muscle had insignificant effects on meat colour and water holding capacity (p>0.05). The variation of meat quality of yak from breed is up to 59.46% of total variation according to PCA. It is shown that the difference between breeds, for Gannan yak and Sibu yak, plays an important role in carcass size performance and meat quality. PMID- 27194932 TI - Effects of Edible Films Containing Procyanidin on the Preservation of Pork Meat during Chilled Storage. AB - Procyanidins, which are natural antioxidants and antimicrobials found in grapes, enhance the quality and extend the shelf life of meat. We explored the effects of edible films incorporating procyanidins on pork loin stored for various times. Procyanidins (0, 0.1, and 0.3%, w/w) were incorporated into the edible films. We assessed meat color, pH, levels of volatile basic nitrogen (VBN) and 2 thiobarbituric acid-reactive substances (TBARS), and microbial populations for 14 d. The chromaticities and pH values of pork loin wrapped in film containing procyanidins (0.1% and 0.3%) generally increased (p<0.05) with storage time. VBN and TBARS levels, and total bacterial and Escherichia coli (E. coli) counts, significantly decreased (p<0.05) in the procyanidin groups. In particular, procyanidins strongly inhibited TBARS formation. Thus, our findings suggest that edible film impregnated with procyanidins inhibits lipid oxidation and microbial growth, thereby enhancing the quality and shelf life of pork meat. PMID- 27194933 TI - Anti-Aging Effects of the Hanwoo Leg Bone, Foot and Tail Infusions (HLI, HFI and HTI) on Skin Fibroblast. AB - Many researchers revealed that collagen contribute to maintaining the skin's elasticity and inhibit wrinkling of skin. Korean native cattle (Hanwoo) bone (leg bone, foot and tail) infusion contains the various inorganic materials, collagen and chondroitin sulfate. All of this, a large quantity of collagen is included in Hanwoo infusion. Therefore, this study emphasized on the effects of collagen in the Hanwoo bone infusion. For the first time, Hanwoo bone infusions were directly added to the media of Human Dermal Fibroblast (NHDF-c) to test anti-aging effects. First, it was identified that growth rate of skin fibroblast was increased. Furthermore, the Hanwoo bone infusion increased a 50% of fibroblast collagen synthesis. Also, suppression of skin fibroblast aging was confirmed by treatment Hanwoo bone infusion. In conclusion, this study demonstrates the effects of infusion made from Hanwoo leg bone, foot and tail on anti-aging, wrinkle inhibiting and skin fibroblast elasticity maintaining. Therefore, this study identified that traditional infusion has effects that are good for skin elasticity. PMID- 27194934 TI - Physicochemical and Sensory Properties of Appenzeller Cheese Supplemented with Powdered Microcapsule of Tomato Extract during Ripening. AB - The objective of this study was to determine the physicochemical and sensory properties of Appenzeller cheese supplemented with different concentrations (0, 1, 2, 3, and 4%, w/w) of powdered microcapsules of tomato extracts (PMT) during ripening at 14C for 6 mon. The particle sizes of PMT ranged from 1 to 10 m diameter with an average particle size of approximately 2 m. Butyric acid (C4) concentrations of PMT-added Appenzeller cheese were significantly higher than that of the control. Lactic acid bacteria counts in the cheese were not significantly influenced by ripening time from 0 to 6 mon or the concentrations (0-4%, w/w) of PMT. In terms of texture, the hardness of PMT-added Appenzeller cheese was significantly increased compared to the control. The gumminess and chewiness of PMT-added Appenzeller cheese were similar to those of the control. However, both cohesiveness and springiness of PMT-added Appenzeller cheese were slightly decreased. In sensory analysis, bitterness and sourness of Appenzeller cheese were not significantly changed after supplementation of PMT, but sweetness of the cheese was significantly increased after increasing the ripening time from 0 to 6 mon and increasing the concentration from 1 to 4% (w/w). Based on these results, the addition of the concentrations (1-4%, w/w) of PMT to Appenzeller cheese can be used to develop functional Appenzeller cheese. PMID- 27194935 TI - Analysis of Methionine Oxidation in Myosin Isoforms in Porcine Skeletal Muscle by LC-MS/MS Analysis. AB - The purpose of this study was to analyze oxidized methionines in the myosin isoforms of porcine longissimus thoracis, psoas major, and semimembranosus muscles by liquid chromatography (LC) and mass spectrometry (MS). A total of 836 queries matched to four myosin isoforms (myosin-1, -2, -4, and -7) were analyzed and each myosin isoform was identified by its unique peptides (7.3-13.3). Forty four peptides were observed from all three muscles. Seventeen peptides were unique to the myosin isoform and the others were common peptides expressed in two or more myosin isoforms. Five were identified as oxidized peptides with one or two methionine sulfoxides with 16 amu of mass modification. Methionines on residues 215 (215), 438 (438), 853 (851), 856 (854), 1071 (1069), and 1106 (1104) of myosin-1 (myosin-4) were oxidized by the addition of oxygen. Myosin-2 had two oxidized methionines on residues 215 and 438. No queries matched to myosin-7 were observed as oxidized peptides. LC-MS/MS allows analysis of the oxidation of specific amino acids on specific residue sites, as well as in specific proteins in the food system. PMID- 27194936 TI - Kinetic Behavior of Salmonella on Low NaNO2 Sausages during Aerobic and Vacuum Storage. AB - This study evaluated the growth kinetics of Salmonella spp. in processed meat products formulated with low sodium nitrite (NaNO2). A 5-strain mixture of Salmonella spp. was inoculated on 25-g samples of sausages formulated with sodium chloride (NaCl) (1.0%, 1.25%, and 1.5%) and NaNO2 (0 and 10 ppm) followed by aerobic or vacuum storage at 10C and 15C for up to 816 h or 408 h, respectively. The bacterial cell counts were enumerated on xylose lysine deoxycholate agar, and the modified Gompertz model was fitted to the Salmonella cell counts to calculate the kinetic parameters as a function of NaCl concentration on the growth rate (GR; Log CFU/g/h) and lag phase duration (LPD; h). A linear equation was then fitted to the parameters to evaluate the effect of NaCl concentration on the kinetic parameters. The GR values of Salmonella on sausages were higher (p<0.05) with 10 ppm NaNO2 concentration than with 0 ppm NaNO2. The GR values of Salmonella decreased (p<0.05) as NaCl concentration increased, especially at 10C. This result indicates that 10 ppm NaNO2 may increase Salmonella growth at low NaCl concentrations, and that NaCl plays an important role in inhibiting Salmonella growth in sausages with low NaNO2. PMID- 27194937 TI - Physicochemical Characterization and Potential Prebiotic Effect of Whey Protein Isolate/Inulin Nano Complex. AB - The purposes of this study were to investigate the impacts of concentration levels of whey protein isolate (WPI) and inulin on the formation and physicochemical properties of WPI/inulin nano complexes and to evaluate their potential prebiotic effects. WPI/inulin nano complexes were produced using the internal gelation method. Transmission electron microscopy (TEM) and particle size analyzer were used to assess the morphological and physicochemical characterizations of nano complexes, respectively. The encapsulation efficiency of resveratrol in nano complexes was studied using HPLC while the potential prebiotic effects were investigated by measuring the viability of probiotics. In TEM micrographs, the globular forms of nano complexes in the range of 10 and 100 nm were successfully manufactured. An increase in WPI concentration level from 1 to 3% (w/v) resulted in a significant (p<0.05) decrease in the size of nano complexs while inulin concentration level did not affect the size of nano complexes. The polydispersity index of nano complexes was below 0.3 in all cases while the zeta-potential values in the range of -2 and -12 mV were observed. The encapsulation efficiency of resveratrol was significantly (p<0.05) increased as WPI and inulin concentration levels were increased from 1 to 3% (w/v). During incubation at 37C for 24 h, WPI/inulin nano complexes exhibited similar viability of probiotics with free inulin and had significantly (p<0.05) higher viability than negative control. In conclusions, WPI and inulin concentration levels were key factors affecting the physicochemical properties of WPI/inulin nano complexes and had potential prebiotic effect. PMID- 27194939 TI - Identification of Microorganisms in Duck Meat Products Available in Korea and the Effect of High Hydrostatic Pressure. AB - The objective of this study was to investigate the microbial count of duck meat and duck meat products commercially available in Korea. High hydrostatic pressure (HHP) treatment was applied at 0.1, 300, 400, and 500 MPa for 5 min to enhance the microbiological safety of duck meats. The levels of total aerobic bacteria were in the ranges of 3.53-6.19 and 3.62-6.85 Log CFU/g in raw and smoked duck products, respectively. By DNA sequence analysis, we identified microorganisms responsible for spoilage, with the most common species in the raw and smoked duck products being Aeromonas spp. or Pseudomonas spp. and Leuconostoc mesenteroides, respectively. HHP treatment significantly reduced the levels of total aerobic bacteria in raw and smoked duck products. This study demonstrates that HHP treatment may be used to effectively improve the safety of raw and smoked duck meat products. PMID- 27194940 TI - Witnessing the elimination of magic wands. AB - This paper discusses static verification of programs that have been specified using separation logic with magic wands. Magic wands are used to specify incomplete resources in separation logic, i.e., if missing resources are provided, a magic wand allows one to exchange these for the completed resources. One of the applications of the magic wand operator is to describe loop invariants for algorithms that traverse a data structure, such as the imperative version of the tree delete problem (Challenge 3 from the VerifyThis@FM2012 Program Verification Competition), which is the motivating example for our work. Most separation logic-based static verification tools do not provide support for magic wands, possibly because validity of formulas containing the magic wand is, by itself, undecidable. To avoid this problem, in our approach the program annotator has to provide a witness for the magic wand, thus circumventing undecidability due to the use of magic wands. A witness is an object that encodes both instructions for the permission exchange that is specified by the magic wand and the extra resources needed during that exchange. We show how this witness information is used to encode a specification with magic wands as a specification without magic wands. Concretely, this approach is used in the VerCors tool set: annotated Java programs are encoded as Chalice programs. Chalice then further translates the program to BoogiePL, where appropriate proof obligations are generated. Besides our encoding of magic wands, we also discuss the encoding of other aspects of annotated Java programs into Chalice, and in particular, the encoding of abstract predicates with permission parameters. We illustrate our approach on the tree delete algorithm, and on the verification of an iterator of a linked list. PMID- 27194938 TI - Anti-Oxidative and Anti-Inflammation Activities of Pork Extracts. AB - This study was conducted to evaluate the antioxidative and anti-inflammatory effects of boiled pork powder (BPP) and hot water extract powder (HWEP) from 4 cuts of meat from Landrace * Yorkshire * Duroc (LYD). The highest DPPH radical scavenging activities determined were from BPP of Boston butt (13.65 M TE) and HWEP of loin (19.40 M TE) and ham (21.45 M TE). The 2,2-azino-bis-3 ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging activities of BPP from shoulder ham (39.28 M TE) and ham (39.43 M TE) were higher than those of other meat cuts, while HWEP of ham exhibited the highest ABTS radical scavenging activity. A higher oxygen radical absorbance capacity was determined for BPP from ham (198.35 M TE) and in HWEP from loin (204.07 M TE), Boston butt (192.85 M TE), and ham (201.36 M TE). Carnosine content of BPP and HWEP from loin and were determined to be 106.68 and 117.77 mg/g on a dry basis, respectively. The anserine content of BPP (5.26 mg/g, dry basis) and HWEP (6.79 mg/g, dry basis) of shoulder ham exhibited the highest value as compared to the extracts from the other meat cuts. The viability of RAW 264.7 cells was increased with increasing HWEP from loin and ham treatment. In addition, the expression of IL-6 and TNF alpha was significantly reduced by HWEP from loin and ham, in a dose dependent manner. These results suggested that boiled pork and hot water extract of pork have antioxidative and cytokine inhibitory effects. PMID- 27194941 TI - In Vitro Antileukemia Activity of ZSTK474 on K562 and Multidrug Resistant K562/A02 Cells. AB - Chronic myelogenous leukemia (CML) is a malignant hematological disorder mainly caused by the Bcr-Abl tyrosine kinase. While Bcr-Abl inhibitors including Imatinib showed antitumor efficacy on many CML patients, resistance was frequently reported in recent years. Therefore, novel drugs for CML are still expected. ZSTK474 is a specific phosphatidylinositol 3-kinase (PI3K) inhibitor that we identified. In the present study, the efficacy of ZSTK474, alone or in combination with Imatinib, on K562 CML cells as well as on its multidrug resistance counterpart K562/A02 cells, was investigated. ZSTK474 inhibited the cell proliferation with an IC50 of 4.69 MUM for K562 and 7.57 MUM for K562/A02 cells, respectively. Treatment by ZSTK474 resulted in cell cycle arrest in G1 phase, which might be associated with upregulation of p27, and downregulation of cyclin D1. ZSTK474 also inhibited phosphorylation of Akt and GSK-3beta, which might be involved in the effect on the above cell cycle-related proteins. Moreover, combination of ZSTK474 and Imatinib indicated synergistic effect on both cell lines. In conclusion, ZSTK474 exhibited antileukemia activity alone, and showed synergistic effect when combined with Imatinib, on CML K562 cells as well as the multidrug resistant ones, providing a potential therapeutic approach for CML patients. PMID- 27194942 TI - Dimethyloxaloylglycine Promotes the Angiogenic Activity of Mesenchymal Stem Cells Derived from iPSCs via Activation of the PI3K/Akt Pathway for Bone Regeneration. AB - The vascularization of tissue-engineered bone is a prerequisite step for the successful repair of bone defects. Hypoxia inducible factor-1alpha (HIF-1alpha) plays an essential role in angiogenesis-osteogenesis coupling during bone regeneration and can activate the expression of angiogenic factors in mesenchymal stem cells (MSCs). Dimethyloxaloylglycine (DMOG) is an angiogenic small molecule that can inhibit prolyl hydroxylase (PHD) enzymes and thus regulate the stability of HIF-1alpha in cells at normal oxygen tension. Human induced pluripotent stem cell-derived MSCs (hiPSC-MSCs) are promising alternatives for stem cell therapy. In this study, we evaluated the effect of DMOG on promoting hiPSC-MSCs angiogenesis in tissue-engineered bone and simultaneously explored the underlying mechanisms in vitro. The effectiveness of DMOG in improving the expression of HIF 1alpha and its downstream angiogenic genes in hiPSC-MSCs demonstrated that DMOG significantly enhanced the gene and protein expression profiles of angiogenic related factors in hiPSC-MSCs by sustaining the expression of HIF-1alpha. Further analysis showed that DMOG-stimulated hiPSC-MSCs angiogenesis was associated with the phosphorylation of protein kinase B (Akt) and with an increase in VEGF production. The effects could be blocked by the addition of the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. In a critical-sized calvarial defect model in rats, DMOG-treated hiPSC-MSCs showed markedly improved angiogenic capacity in the tissue-engineered bone, leading to bone regeneration. Collectively, the results indicate that DMOG, via activation of the PI3K/Akt pathway, promotes the angiogenesis of hiPSC-MSCs in tissue-engineered bone for bone defect repair and that DMOG-treated hiPSC-MSCs can be exploited as a potential therapeutic tool in bone regeneration. PMID- 27194945 TI - A Novel Role of Cab45-G in Mediating Cell Migration in Cancer Cells. AB - Ca(2+)-binding protein of 45 kDa (Cab45), a CREC family member, is reported to be associated with Ca(2+)-dependent secretory pathways and involved in multiple diseases including cancers. Cab45-G, a Cab45 isoform protein, plays an important role in protein sorting and secretion at Golgi complex. However, its role in cancer cell migration remains elusive. In this study, we demonstrate that Cab45-G exhibited an increased expression in cell lines with higher metastatic potential and promoted cell migration in multiple types of cancer cells. Overexpression of Cab45-G resulted in an altered expression of the molecular mediators of epithelial-mesenchymal transition (EMT), which is a critical step in the tumor metastasis. Quantitative real-time PCR showed that overexpression of Cab45-G increased the expression of matrix metalloproteinase-2 and -7 (MMP-2 and MMP-7). Conversely, knock-down of Cab45-G reduced the expression of the above MMPs. Moreover, forced expression of Cab45-G upregulated the level of phosphorylated ERK and modulated the secretion of extracellular proteins fibronectin and fibulin. Furthermore, in human cervical and esophageal cancer tissues, the expression of Cab45-G was found to be significantly correlated with that of MMP 2, further supporting the importance of Cab45-G on regulating cancer metastasis. Taken together, these results suggest that Cab45-G could regulate cancer cell migration through various molecular mechanisms, which may serve as a therapeutic target for the treatment of cancers. PMID- 27194944 TI - Partial Mullerian Duct Retention in Smad4 Conditional Mutant Male Mice. AB - Mullerian duct regression is a complex process which involves the AMH signalling pathway. We have previously demonstrated that besides AMH and its specific type II receptor (AMHRII), BMPR-IA and Smad5 are two essential factors implicated in this mechanism. Mothers against decapentaplegic homolog 4 (Smad4) is a transcription factor and the common Smad (co-Smad) involved in transforming growth factor beta (TGF-beta) signalling pathway superfamily. Since Smad4 null mutants die early during gastrulation, we have inactivated Smad4 in the Mullerian duct mesenchyme. Specific inactivation of Smad4 in the urogenital ridge leads to the partial persistence of the Mullerian duct in adult male mice. Careful examination of the urogenital tract reveals that the Mullerian duct retention is randomly distributed either on one side or both sides. Histological analysis shows a uterus-like structure, which is confirmed by the expression of estrogen receptor alpha. As previously described in a beta-catenin conditional mutant mouse model, beta-catenin contributes to Mullerian duct regression. In our mutant male embryos, it appears that beta-catenin expression is locally reduced along the urogenital ridge as compared to control mice. Moreover, the expression pattern is similar to those observed in control female mice. This study shows that reduced Smad4 expression disrupts the Wnt/beta-catenin signalling leading to the partial persistence of Mullerian duct. PMID- 27194943 TI - RNA-Seq and iTRAQ Reveal the Dwarfing Mechanism of Dwarf Polish Wheat (Triticum polonicum L.). AB - The dwarfing mechanism of Rht-dp in dwarf Polish wheat (DPW) is unknown. Each internode of DPW was significantly shorter than it in high Polish wheat (HPW), and the dwarfism was insensitive to photoperiod, abscisic acid (ABA), gibberellin (GA), cytokinin (CK), auxin and brassinolide (BR). To understand the mechanism, three sets of transcripts, DPW, HPW, and a chimeric set (a combination of DPW and HPW), were constructed using RNA sequencing (RNA-Seq). Based on the chimeric transcripts, 2,446 proteins were identified using isobaric tags for relative and absolute quantification (iTRAQ). A total of 108 unigenes and 12 proteins were considered as dwarfism-related differentially expressed genes (DEGs) and differentially expressed proteins (DEPs), respectively. Among of these DEGs and DEPs, 6 DEGs and 6 DEPs were found to be involved in flavonoid and S-adenosyl methionine (SAM) metabolisms; 5 DEGs and 3 DEPs were involved in cellulose metabolism, cell wall plasticity and cell expansion; 2 DEGs were auxin transporters; 2 DEPs were histones; 1 DEP was a peroxidase. These DEGs and DEPs reduced lignin and cellulose contents, increased flavonoid content, possibly decreased S-adenosyl-methionine (SAM) and polyamine contents and increased S adenosyl-L-homocysteine hydrolase (SAHH) content in DPW stems, which could limit auxin transport and reduce extensibility of the cell wall, finally limited cell expansion (the cell size of DPW was significantly smaller than HPW cells) and caused dwarfism in DPW. PMID- 27194946 TI - Ubisol-Q10 Prevents Glutamate-Induced Cell Death by Blocking Mitochondrial Fragmentation and Permeability Transition Pore Opening. AB - Mitochondrial dysfunction and oxidative stress are the major events that lead to the formation of mitochondrial permeability transition pore (mPTP) during glutamate-induced cytotoxicity and cell death. Coenzyme Q10 (CoQ10) has widely been used for the treatment of mitochondrial disorders and neurodegenerative diseases. Comparing to traditional lipid-soluble CoQ10, water soluble CoQ10 (Ubisol-Q10) has high intracellular and intra-mitochondrial distribution. The aims of the present study are to determine the neuroprotective effects of Ubisol Q10 on glutamate-induced cell death and to explore its functional mechanisms. HT22 neuronal cells were exposed to glutamate. Cell viability was measured and mitochondrial fragmentation was assessed by mitochondrial imaging. The mPTP opening was determined by mitochondrial membrane potential and calcium retention capacity. The results revealed that the anti-glutamate toxicity effects of Ubisol Q10 was associated with its ability to block mitochondrial fragmentation, to maintain calcium retention capacity and mitochondrial membrane potential, and to prevent mPTP formation, AIF release, and DNA fragmentation. We concluded that Ubisol-Q10 protects cells from glutamate toxicity by preserving the integrity of mitochondrial structure and function. Therefore, adequate CoQ10 supplementation may be beneficial in preventing cerebral stroke and other disorders that involve mitochondrial dysfunction. PMID- 27194947 TI - Ribose Accelerates Gut Motility and Suppresses Mouse Body Weight Gaining. AB - The increasing prevalence of obesity is closely related to excessive energy consumption. Clinical intervention of energy intake is an attractive strategy to fight obesity. However, the current FDA-approved weight-loss drugs all have significant side effects. Here we show that ribose upregulates gut motility and suppresses mice body weight gain. Ribokinase, which is encoded by Rbks gene, is the first enzyme for ribose metabolism in vivo. Rbks mutation resulted in ribose accumulation in the small intestine, which accelerated gut movement. Ribose oral treatment in wild type mice also enhanced bowel motility and rendered mice resistance to high fat diets. The suppressed weight gain was resulted from enhanced ingested food excretion. In addition, the effective dose of ribose didn't cause any known side effects (i.e. diarrhea and hypoglycemia). Overall, our results show that ribose can regulate gut motility and energy homeostasis in mice, and suggest that administration of ribose and its analogs could regulate gastrointestinal motility, providing a novel therapeutic approach for gastrointestinal dysfunction and weight control. PMID- 27194948 TI - Interleukin-10 Family and Tuberculosis: An Old Story Renewed. AB - The interleukin-10 (IL-10) family of cytokines consists of six immune mediators, namely IL-10, IL-19, IL-20, IL-22, IL-24 and IL-26. IL-10, IL-22, IL-24 and IL-26 are critical for the regulation of host defense against Mycobacterium tuberculosis infections. Specifically, IL-10 and IL-26 can suppress the antimycobacterial immunity and promote the survival of pathogen, while IL-22 and IL-24 can generate protective responses and inhibit the intracellular growth of pathogen. Knowledge about the new players in tuberculosis immunology, namely IL 10 family, can inform novel immunity-based countermeasures and host directed therapies against tuberculosis. PMID- 27194950 TI - Different Modulatory Mechanisms of Renal FXYD12 for Na(+)-K(+)-ATPase between Two Closely Related Medakas upon Salinity Challenge. AB - Upon salinity challenge, the Na(+)-K(+)-ATPase (NKA) of fish kidney plays a crucial role in maintaining ion and water balance. Moreover, the FXYD protein family was found to be a regulator of NKA. Our preliminary results revealed that fxyd12 was highly expressed in the kidneys of the two closely related euryhaline medaka species (Oryzias dancena and O. latipes) from different natural habitats (brackish water and fresh water). In this study, we investigated the expression and association of renal FXYD12 and NKA alpha-subunit as well as potential functions of FXYD12 in the two medakas. These findings illustrated and compared the regulatory roles of FXYD12 for NKA in kidneys of the two medakas in response to salinity changes. In this study, at the mRNA and/or protein level, the expression patterns were similar for renal FXYD12 and NKA in the two medakas. However, different patterns of NKA activities and different interaction levels between FXYD12 and NKA were found in the kidneys of these two medakas. The results revealed that different strategies were used in the kidneys of the two medaka species upon salinity challenge. On the other hand, gene knockdown experiments demonstrated that the function of O. dancena FXYD12 allowed maintenance of a high level of NKA activity. The results of the present study indicated that the kidneys of the examined euryhaline medakas originating from brackish water and fresh water exhibited different modulatory mechanisms through which renal FXYD12 enhanced NKA activity to maintain internal homeostasis. Our findings broadened the knowledge of expression and functions of FXYD proteins, the modulators of NKA, in vertebrates. PMID- 27194952 TI - A Novel Protein Elicitor (PeBA1) from Bacillus amyloliquefaciens NC6 Induces Systemic Resistance in Tobacco. AB - Here we reported a novel protein elicitor from Bacillus amyloliquefaciens NC6 induced systemic resistance (ISR) in tobacco. The purification was executed by ion-exchange chromatography, native-page extraction and HPLC, and the amino acid sequence was identified by mass spectrometry. This recombinant elicitor protein, expressed in Escherichia coli by an E1 expression vector, had good thermal stability, and the elicitor caused a clearly defined hypersensitive response (HR) necrosis in tobacco leaves. It could also trigger early defence events, including generation of reactive oxygen species (H2O2 and O2 (-)) and phenolic-compound accumulation. Quantitative real-time PCR (Q-RT-PCR) results indicated that several plant defence genes, including the salicylic acid (SA)-responsive PR1a, PR1b, PR5, and phenylalanine ammonia lyase (PAL), as well as the jasmonic acid (JA)-responsive PDF1.2 and CORONATINE INSENSITIVE 1 (COI1), were all up regulated. Moreover, infiltration conferred systemic resistance against a broad spectrum of pathogens, including Tobacco mosaic virus (TMV) and the fungal pathogen Botrytis cinerea. PMID- 27194951 TI - Chemoprevention of Low-Molecular-Weight Citrus Pectin (LCP) in Gastrointestinal Cancer Cells. AB - BACKGROUND & AIMS: Low-molecular-weight citrus pectin (LCP) is a complex polysaccharide that displays abundant galactosyl (i.e., sugar carbohydrate) residues. In this study, we evaluated the anti-tumor properties of LCP that lead to Bcl-xL -mediated dampening of apoptosis in gastrointestinal cancer cells. METHODS: We used AGS gastric cancer and SW-480 colorectal cancer cells to elucidate the effects of LCP on cell viability, cell cycle and apoptosis in cultured cells and tumor xenografts. RESULTS: Significantly decreased cell viabilities were observed in LCP treated AGS and SW-480 cells (P<0.05). Cell cycle-related protein expression, such as Cyclin B1, was also decreased in LCP treated groups as compared to the untreated group. The AGS or SW-480 cell-line tumor xenografts were significantly smaller in the LCP treated group as compared the untreated group (P<0.05). LCP treatment decreased Galectin-3 (GAL-3) expression levels, which is an important gene in cancer metastasis that results in reversion of the epithelial-mesenchymal transition (EMT), and increased suppression of Bcl-xL and Survivin to promote apoptosis. Moreover, results demonstrated synergistic tumor suppressor activity of LCP and 5-FU against gastrointestinal cancer cells both in vivo and in vitro. CONCLUSIONS: LCP effectively inhibits the growth and metastasis of gastrointestinal cancer cells, and does so in part by down-regulating Bcl-xL and Cyclin B to promote apoptosis, and suppress EMT. Thus, LCP alone or in combination with other treatments has a high potential as a novel therapeutic strategy to improve the clinical therapy of gastrointestinal cancer. PMID- 27194949 TI - New Strategies for the Treatment of Solid Tumors with CAR-T Cells. AB - Recent years, we have witnessed significant progresses in both basic and clinical studies regarding novel therapeutic strategies with genetically engineered T cells. Modification with chimeric antigen receptors (CARs) endows T cells with tumor specific cytotoxicity and thus induce anti-tumor immunity against malignancies. However, targeting solid tumors is more challenging than targeting B-cell malignancies with CAR-T cells because of the histopathological structure features, specific antigens shortage and strong immunosuppressive environment of solid tumors. Meanwhile, the on-target/off-tumor toxicity caused by relative expression of target on normal tissues is another issue that should be reckoned. Optimization of the design of CAR vectors, exploration of new targets, addition of safe switches and combination with other treatments bring new vitality to the CAR-T cell based immunotherapy against solid tumors. In this review, we focus on the major obstacles limiting the application of CAR-T cell therapy toward solid tumors and summarize the measures to refine this new cancer therapeutic modality. PMID- 27194953 TI - Discovery and Characterization of Iron Sulfide and Polyphosphate Bodies Coexisting in Archaeoglobus fulgidus Cells. AB - Inorganic storage granules have long been recognized in bacterial and eukaryotic cells but were only recently identified in archaeal cells. Here, we report the cellular organization and chemical compositions of storage granules in the Euryarchaeon, Archaeoglobus fulgidus strain VC16, a hyperthermophilic, anaerobic, and sulfate-reducing microorganism. Dense granules were apparent in A. fulgidus cells imaged by cryo electron microscopy (cryoEM) but not so by negative stain electron microscopy. Cryo electron tomography (cryoET) revealed that each cell contains one to several dense granules located near the cell membrane. Energy dispersive X-ray (EDX) spectroscopy and scanning transmission electron microscopy (STEM) show that, surprisingly, each cell contains not just one but often two types of granules with different elemental compositions. One type, named iron sulfide body (ISB), is composed mainly of the elements iron and sulfur plus copper; and the other one, called polyphosphate body (PPB), is composed of phosphorus and oxygen plus magnesium, calcium, and aluminum. PPBs are likely used for energy storage and/or metal sequestration/detoxification. ISBs could result from the reduction of sulfate to sulfide via anaerobic energy harvesting pathways and may be associated with energy and/or metal storage or detoxification. The exceptional ability of these archaeal cells to sequester different elements may have novel bioengineering applications. PMID- 27194955 TI - Astrospheres and Solar-like Stellar Winds. AB - Stellar analogs for the solar wind have proven to be frustratingly difficult to detect directly. However, these stellar winds can be studied indirectly by observing the interaction regions carved out by the collisions between these winds and the interstellar medium (ISM). These interaction regions are called "astrospheres", analogous to the "heliosphere" surrounding the Sun. The heliosphere and astrospheres contain a population of hydrogen heated by charge exchange processes that can produce enough H I Lyalpha absorption to be detectable in UV spectra of nearby stars from the Hubble Space Telescope (HST). The amount of astrospheric absorption is a diagnostic for the strength of the stellar wind, so these observations have provided the first measurements of solar like stellar winds. Results from these stellar wind studies and their implications for our understanding of the solar wind are reviewed here. Of particular interest are results concerning the past history of the solar wind and its impact on planetary atmospheres. PMID- 27194956 TI - Infrared Solar Physics. AB - The infrared solar spectrum contains a wealth of physical data about our Sun, and is explored using modern detectors and technology with new ground-based solar telescopes. The scientific motivation behind exploring these wavelengths is presented, along with a brief look at the rich history of observations here. Several avenues of solar physics research exploiting and benefiting from observations at infrared wavelengths from roughly 1000 nm to 12 400 nm are discussed, and the instrument and detector technology driving this research is briefly summarized. Finally, goals for future work at infrared wavelengths are presented in conjunction with ground and space-based observations. PMID- 27194954 TI - A microfluidic approach to parallelized transcriptional profiling of single cells. AB - The ability to correlate single-cell genetic information with cellular phenotypes is of great importance to biology and medicine, as it holds the potential to gain insight into disease pathways that is unavailable from ensemble measurements. We present a microfluidic approach to parallelized, rapid, quantitative analysis of messenger RNA from single cells via RT-qPCR. The approach leverages an array of single-cell RT-qPCR analysis units formed by a set of parallel microchannels concurrently controlled by elastomeric pneumatic valves, thereby enabling parallelized handling and processing of single cells in a drastically simplified operation procedure using a relatively small number of microvalves. All steps for single-cell RT-qPCR, including cell isolation and immobilization, cell lysis, mRNA purification, reverse transcription and qPCR, are integrated on a single chip, eliminating the need for off-chip manual cell and reagent transfer and qPCR amplification as commonly used in existing approaches. Additionally, the approach incorporates optically transparent microfluidic components to allow monitoring of single-cell trapping without the need for molecular labeling that can potentially alter the targeted gene expression and utilizes a polycarbonate film as a barrier against evaporation to minimize the loss of reagents at elevated temperatures during the analysis. We demonstrate the utility of the approach by the transcriptional profiling for the induction of the cyclin-dependent kinase inhibitor 1a and the glyceraldehyde 3-phosphate dehydrogenase in single cells from the MCF-7 breast cancer cell line. Furthermore, the methyl methanesulfonate is employed to allow measurement of the expression of the genes in individual cells responding to a genotoxic stress. PMID- 27194957 TI - Coronal Loops: Observations and Modeling of Confined Plasma. AB - Coronal loops are the building blocks of the X-ray bright solar corona. They owe their brightness to the dense confined plasma, and this review focuses on loops mostly as structures confining plasma. After a brief historical overview, the review is divided into two separate but not independent parts: the first illustrates the observational framework, the second reviews the theoretical knowledge. Quiescent loops and their confined plasma are considered and, therefore, topics such as loop oscillations and flaring loops (except for non solar ones, which provide information on stellar loops) are not specifically addressed here. The observational section discusses the classification, populations, and the morphology of coronal loops, its relationship with the magnetic field, and the loop stranded structure. The section continues with the thermal properties and diagnostics of the loop plasma, according to the classification into hot, warm, and cool loops. Then, temporal analyses of loops and the observations of plasma dynamics, hot and cool flows, and waves are illustrated. In the modeling section, some basics of loop physics are provided, supplying fundamental scaling laws and timescales, a useful tool for consultation. The concept of loop modeling is introduced and models are divided into those treating loops as monolithic and static, and those resolving loops into thin and dynamic strands. More specific discussions address modeling the loop fine structure and the plasma flowing along the loops. Special attention is devoted to the question of loop heating, with separate discussion of wave (AC) and impulsive (DC) heating. Large-scale models including atmosphere boxes and the magnetic field are also discussed. Finally, a brief discussion about stellar coronal loops is followed by highlights and open questions. PMID- 27194958 TI - The Solar Cycle. AB - : The solar cycle is reviewed. The 11-year cycle of solar activity is characterized by the rise and fall in the numbers and surface area of sunspots. A number of other solar activity indicators also vary in association with the sunspots including; the 10.7 cm radio flux, the total solar irradiance, the magnetic field, flares and coronal mass ejections, geomagnetic activity, galactic cosmic ray fluxes, and radioisotopes in tree rings and ice cores. Individual solar cycles are characterized by their maxima and minima, cycle periods and amplitudes, cycle shape, the equatorward drift of the active latitudes, hemispheric asymmetries, and active longitudes. Cycle-to-cycle variability includes the Maunder Minimum, the Gleissberg Cycle, and the Gnevyshev-Ohl (even odd) Rule. Short-term variability includes the 154-day periodicity, quasi biennial variations, and double-peaked maxima. We conclude with an examination of prediction techniques for the solar cycle and a closer look at cycles 23 and 24. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/lrsp-2015-4. PMID- 27194959 TI - Flare Observations. AB - : Solar flares are observed at all wavelengths from decameter radio waves to gamma-rays at 100 MeV. This review focuses on recent observations in EUV, soft and hard X-rays, white light, and radio waves. Space missions such as RHESSI, Yohkoh, TRACE, and SOHO have enlarged widely the observational base. They have revealed a number of surprises: Coronal sources appear before the hard X-ray emission in chromospheric footpoints, major flare acceleration sites appear to be independent of coronal mass ejections (CMEs), electrons, and ions may be accelerated at different sites, there are at least 3 different magnetic topologies, and basic characteristics vary from small to large flares. Recent progress also includes improved insights into the flare energy partition, on the location(s) of energy release, tests of energy release scenarios and particle acceleration. The interplay of observations with theory is important to deduce the geometry and to disentangle the various processes involved. There is increasing evidence supporting reconnection of magnetic field lines as the basic cause. While this process has become generally accepted as the trigger, it is still controversial how it converts a considerable fraction of the energy into non-thermal particles. Flare-like processes may be responsible for large-scale restructuring of the magnetic field in the corona as well as for its heating. Large flares influence interplanetary space and substantially affect the Earth's lower ionosphere. While flare scenarios have slowly converged over the past decades, every new observation still reveals major unexpected results, demonstrating that solar flares, after 150 years since their discovery, remain a complex problem of astrophysics including major unsolved questions. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.12942/lrsp-2008-1. PMID- 27194960 TI - Solar Surface Convection. AB - : We review the properties of solar convection that are directly observable at the solar surface, and discuss the relevant underlying physics, concentrating mostly on a range of depths from the temperature minimum down to about 20 Mm below the visible solar surface. The properties of convection at the main energy carrying (granular) scales are tightly constrained by observations, in particular by the detailed shapes of photospheric spectral lines and the topology (time- and length-scales, flow velocities, etc.) of the up- and downflows. Current supercomputer models match these constraints very closely, which lends credence to the models, and allows robust conclusions to be drawn from analysis of the model properties. At larger scales the properties of the convective velocity field at the solar surface are strongly influenced by constraints from mass conservation, with amplitudes of larger scale horizontal motions decreasing roughly in inverse proportion to the scale of the motion. To a large extent, the apparent presence of distinct (meso- and supergranulation) scales is a result of the folding of this spectrum with the effective "filters" corresponding to various observational techniques. Convective motions on successively larger scales advect patterns created by convection on smaller scales; this includes patterns of magnetic field, which thus have an approximately self-similar structure at scales larger than granulation. Radiative-hydrodynamical simulations of solar surface convection can be used as 2D/3D time-dependent models of the solar atmosphere to predict the emergent spectrum. In general, the resulting detailed spectral line profiles agree spectacularly well with observations without invoking any micro- and macroturbulence parameters due to the presence of convective velocities and atmosphere inhomogeneities. One of the most noteworthy results has been a significant reduction in recent years in the derived solar C, N, and O abundances with far-reaching consequences, not the least for helioseismology. Convection in the solar surface layers is also of great importance for helioseismology in other ways; excitation of the wave spectrum occurs primarily in these layers, and convection influences the size of global wave cavity and, hence, the mode frequencies. On local scales convection modulates wave propagation, and supercomputer convection simulations may thus be used to test and calibrate local helioseismic methods. We also discuss the importance of near solar surface convection for the structure and evolution of magnetic patterns: faculae, pores, and sunspots, and briefly address the question of the importance or not of local dynamo action near the solar surface. Finally, we discuss the importance of near solar surface convection as a driver for chromospheric and coronal heating. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.12942/lrsp-2009-2. PMID- 27194961 TI - Coronal Holes. AB - Coronal holes are the darkest and least active regions of the Sun, as observed both on the solar disk and above the solar limb. Coronal holes are associated with rapidly expanding open magnetic fields and the acceleration of the high speed solar wind. This paper reviews measurements of the plasma properties in coronal holes and how these measurements are used to reveal details about the physical processes that heat the solar corona and accelerate the solar wind. It is still unknown to what extent the solar wind is fed by flux tubes that remain open (and are energized by footpoint-driven wave-like fluctuations), and to what extent much of the mass and energy is input intermittently from closed loops into the open-field regions. Evidence for both paradigms is summarized in this paper. Special emphasis is also given to spectroscopic and coronagraphic measurements that allow the highly dynamic non-equilibrium evolution of the plasma to be followed as the asymptotic conditions in interplanetary space are established in the extended corona. For example, the importance of kinetic plasma physics and turbulence in coronal holes has been affirmed by surprising measurements from the UVCS instrument on SOHO that heavy ions are heated to hundreds of times the temperatures of protons and electrons. These observations point to specific kinds of collisionless Alfven wave damping (i.e., ion cyclotron resonance), but complete theoretical models do not yet exist. Despite our incomplete knowledge of the complex multi-scale plasma physics, however, much progress has been made toward the goal of understanding the mechanisms ultimately responsible for producing the observed properties of coronal holes. PMID- 27194962 TI - Wave Modeling of the Solar Wind. AB - The acceleration and heating of the solar wind have been studied for decades using satellite observations and models. However, the exact mechanism that leads to solar wind heating and acceleration is poorly understood. In order to improve the understanding of the physical mechanisms that are involved in these processes a combination of modeling and observational analysis is required. Recent models constrained by satellite observations show that wave heating in the low-frequency (MHD), and high-frequency (ion-cyclotron) range may provide the necessary momentum and heat input to coronal plasma and produce the solar wind. This review is focused on the results of several recent solar modeling studies that include waves explicitly in the MHD and the kinetic regime. The current status of the understanding of the solar wind acceleration and heating by waves is reviewed. PMID- 27194963 TI - Solar Cycle Prediction. AB - A review of solar cycle prediction methods and their performance is given, including forecasts for cycle 24. The review focuses on those aspects of the solar cycle prediction problem that have a bearing on dynamo theory. The scope of the review is further restricted to the issue of predicting the amplitude (and optionally the epoch) of an upcoming solar maximum no later than right after the start of the given cycle. Prediction methods form three main groups. Precursor methods rely on the value of some measure of solar activity or magnetism at a specified time to predict the amplitude of the following solar maximum. Their implicit assumption is that each numbered solar cycle is a consistent unit in itself, while solar activity seems to consist of a series of much less tightly intercorrelated individual cycles. Extrapolation methods, in contrast, are based on the premise that the physical process giving rise to the sunspot number record is statistically homogeneous, i.e., the mathematical regularities underlying its variations are the same at any point of time and, therefore, it lends itself to analysis and forecasting by time series methods. Finally, instead of an analysis of observational data alone, model based predictions use physically (more or less) consistent dynamo models in their attempts to predict solar activity. In their overall performance during the course of the last few solar cycles, precursor methods have clearly been superior to extrapolation methods. Nevertheless, most precursor methods overpredicted cycle 23, while some extrapolation methods may still be worth further study. Model based forecasts have not yet had a chance to prove their skills. One method that has yielded predictions consistently in the right range during the past few solar cycles is that of K. Schatten et al., whose approach is mainly based on the polar field precursor. The incipient cycle 24 will probably mark the end of the Modern Maximum, with the Sun switching to a state of less strong activity. It will therefore be an important testbed for cycle prediction methods and, by inference, for our understanding of the solar dynamo. PMID- 27194964 TI - Solar Adaptive Optics. AB - : Adaptive optics (AO) has become an indispensable tool at ground-based solar telescopes. AO enables the ground-based observer to overcome the adverse effects of atmospheric seeing and obtain diffraction limited observations. Over the last decade adaptive optics systems have been deployed at major ground-based solar telescopes and revitalized ground-based solar astronomy. The relatively small aperture of solar telescopes and the bright source make solar AO possible for visible wavelengths where the majority of solar observations are still performed. Solar AO systems enable diffraction limited observations of the Sun for a significant fraction of the available observing time at ground-based solar telescopes, which often have a larger aperture than equivalent space based observatories, such as HINODE. New ground breaking scientific results have been achieved with solar adaptive optics and this trend continues. New large aperture telescopes are currently being deployed or are under construction. With the aid of solar AO these telescopes will obtain observations of the highly structured and dynamic solar atmosphere with unprecedented resolution. This paper reviews solar adaptive optics techniques and summarizes the recent progress in the field of solar adaptive optics. An outlook to future solar AO developments, including a discussion of Multi-Conjugate AO (MCAO) and Ground-Layer AO (GLAO) will be given. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.12942/lrsp-2011-2. PMID- 27194965 TI - Magnetic Structure of Sunspots. AB - : In this review we give an overview about the current state-of-knowledge of the magnetic field in sunspots from an observational point of view. We start by offering a brief description of tools that are most commonly employed to infer the magnetic field in the solar atmosphere with emphasis in the photosphere of sunspots. We then address separately the global and local magnetic structure of sunspots, focusing on the implications of the current observations for the different sunspots models, energy transport mechanisms, extrapolations of the magnetic field towards the corona, and other issues. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.12942/lrsp 2011-4. PMID- 27194966 TI - A Loss or a Gain, Is It Not All the Same? PMID- 27194967 TI - SHOX Haploinsufficiency as a Cause of Syndromic and Nonsyndromic Short Stature. AB - SHOX in the short arm pseudoautosomal region (PAR1) of sex chromosomes is one of the major growth genes in humans. SHOX haploinsufficiency results in idiopathic short stature and Leri-Weill dyschondrosteosis and is associated with the short stature of patients with Turner syndrome. The SHOX protein likely controls chondrocyte apoptosis by regulating multiple target genes including BNP,Fgfr3, Agc1, and Ctgf. SHOX haploinsufficiency frequently results from deletions and duplications in PAR1 involving SHOX exons and/or the cis-acting enhancers, while exonic point mutations account for a small percentage of cases. The clinical severity of SHOX haploinsufficiency reflects hormonal conditions rather than mutation types. Growth hormone treatment seems to be beneficial for cases with SHOX haploinsufficiency, although the long-term outcomes of this therapy require confirmation. Future challenges in SHOX research include elucidating its precise function in the developing limbs, identifying additional cis-acting enhancers, and determining optimal therapeutic strategies for patients. PMID- 27194968 TI - Stuve-Wiedemann Syndrome: Update on Clinical and Genetic Aspects. AB - Stuve-Wiedemann syndrome is a rare autosomal recessive disorder characterized by bowed long bones, joint restrictions, dysautonomia, and respiratory and feeding difficulties, leading to death in the neonatal period and infancy in several occasions. Since the first cases in 1971, much has been learned about this condition, including its molecular basis - mutations in the leukemia inhibitory factor receptor gene (LIFR) -, natural history and management possibilities. This review aims to highlight the clinical aspects, radiological features, molecular findings, and management strategies in Stuve-Wiedemann syndrome. PMID- 27194970 TI - A Novel ECM1 Splice Site Mutation in Lipoid Proteinosis: Case Report plus Review of the Literature. AB - Lipoid proteinosis (LP) is an autosomal recessive genodermatosis known to be caused by mutations in ECM1. Nonsense and missense mutations are the most common variations in LP. Up to date, only 6 splice site mutations have been observed. We report on a 26-year-old female LP patient from a Turkish consanguineous family carrying a novel homozygous splice site mutation in intron 8 of the ECM1 gene and summarize the current knowledge on ECM1 mutations and possible genotype-phenotype correlations. PMID- 27194971 TI - A Family with Craniofrontonasal Syndrome and a Mutation (p.G151S) in the EFNB1 Gene: Expanding the Phenotype. AB - Craniofrontonasal syndrome (CFNS) is a rare genetic entity with X-linked dominant inheritance. CFNS is due to mutations in the Ephrin-B1 (EFNB1) gene. It is characterized by brachycephaly, frontonasal dysplasia, palate/lip defects, dental malocclusion, short neck, split nails, syndactyly, toe and finger defects, and minor skeletal defects. Intelligence is usually unaffected. CFNS exhibits unexpected manifestations between males and females as the latter are more affected. Cellular or metabolic interference due to X inactivation explains the more severe phenotype in heterozygous females. One family with several members affected with CFNS and 100 healthy controls were examined. DNA from leukocytes was isolated to analyze the EFNB1 gene. We did molecular modeling to assess the impact of the mutation on the EFNB1-encoded protein. DNA sequencing analysis of the EFNB1 gene of the affected members showed the heterozygous missense mutation c.451G>A in the EFNB1 gene (GRcH38, chrX: 68,839,708; GERP score in hg38 of 9.961). This transition mutation resulted in the substitution of Gly at position 151 by Ser. Analysis of the healthy members of the family and 100 unrelated controls showed a normal sequence of the EFNB1 gene. Phenotypes of the patients in this family differ from the classical CFNS due to the decreased size of sulci and fissures, subarachnoid space and ventricles, and the absence of a cleft lip/palate. PMID- 27194969 TI - Short Stature in Isodicentric Y Chromosome and Three Copies of the SHOX Gene: Clinical Report and Review of Literature. AB - Short stature homeobox gene (SHOX) mutations and pseudoautosomal region 1 (PAR1) deletions encompassing SHOX are known causes of Leri-Weill dyschondrosteosis and isolated short stature, while 3 copies of SHOX in cases with triple sex chromosome constitution are responsible for tall stature. Duplications involving SHOX have been rarely reported, and they were found in individuals with short, normal and tall stature. An adopted boy with short stature, isodicentric Y chromosome and 3 copies of SHOX is described. Normal growth hormone (GH) secretion and insulin-like growth factor 1 (IGF1) increase during an IGF1 generation test were found, ruling out impaired GH-IGF1 axis. No other organic or psychiatric causes of impaired growth were found. GH treatment improved linear growth, as reported in children with SHOX haploinsufficiency. This new report and the review of literature support that SHOX duplication may cause short stature, especially in those children with duplications of the 5'SHOX regulatory elements. Chromosome analysis and detailed molecular characterization of the duplicated region should be warranted in individuals with SHOX duplications in order to investigate the presence of occult chromosome imbalance. Additional reports and follow-up till adult height are needed to give conclusions on long-term efficacy and safety of GH treatment in short children with SHOX duplication. PMID- 27194973 TI - Interstitial Chromosome 3p14.1 Deletion due to a Maternal Insertion: Phenotype and Association with Balanced Parental Rearrangement. AB - Interstitial deletions of 3p14p12 are rare chromosome abnormalities. We present a patient with multiple congenital anomalies and a 15.4-Mb interstitial loss of chromosome 3p14p12 detected by chromosomal microarray (CMA). Our patient shared many phenotypic features with other reported cases involving the same region including prominent forehead, short palpebral fissures, hand and foot anomalies, genital abnormalities, and bilateral hearing loss. Given the clinical similarity of these cases with significant overlap of the deleted regions, it is likely that the phenotype is related to the deletion of specific genes within the region. Further molecular cytogenetic investigation revealed that our patient's rearrangement was derived from a cryptic insertion of a segment of chromosome 3p into chromosome 18q in the mother, which was balanced and therefore not visible on the mother's CMA. To our knowledge, this finding has not been previously reported. This case illustrates the importance of using molecular cytogenetics for structural analysis and parental studies. CMA is commonly the first-line study in patients with multiple congenital anomalies; however, it is not the appropriate modality to define a structural rearrangement that may be the cause of a deletion. The use of adjunct studies to define the mechanism of an identified copy number aberration has direct clinical application: to identify the underlying cause of the chromosomal abnormality and to define the recurrence risk. Additionally, this case adds to the current body of work regarding a recurrent phenotype that can be attributed to interstitial chromosome 3p deletions, which may help define the phenotypic implications of deletions in this region and support early clinical management. PMID- 27194972 TI - X-Linked Candidate Genes for a Ciliopathy-Like Disorder. AB - The ability to interrogate the genome via chromosomal microarray and sequencing based technologies has accelerated the ability to rapidly and accurately define etiologies as well as new candidate genes related to genetic conditions. We describe a male patient with a lethal presentation of a multiple congenital anomaly syndrome that appeared consistent with a ciliopathy phenotype. The patient was found to have a novel maternally inherited 1.9-Mb X chromosome deletion including 4 known genes. Presently, the biological functions of these genes are not well delineated. However, at least one of these genes may be a promising candidate gene for this pattern of anomalies based on the function of related genes and information from publicly available copy number variant databases of control and affected individuals. These genes would bear further scrutiny in larger cohorts of patients with similar phenotypes. PMID- 27194974 TI - Four Different Tumors Arising in a Nevus Sebaceous. AB - Nevus sebaceous is known by its association with one or more secondary tumors, but more than three multiple tumors arising from a nevus sebaceous is extremely rare. A 67-year-old female presented with a light brown plaque on the back of her head that contained a dome-shaped black node and an erosive lesion. Histopathological examination showed atypical basaloid cells in the black node. At the periphery of that node, structures resembling follicular germs extruded from interlacing cords in the upper portion and tumor nests with sebocytes were in the lower portion. In the erosive lesion, papillated structures with an apocrine epithelium were observed. In the light brown plaque, enlargement of sebaceous lobules was noted. From those histopathological features, a diagnosis of syringocystadenoma papilliferum, sebaceoma, trichoblastoma and basal cell carcinoma arising from a nevus sebaceous was made. We discuss the rarity of multiple tumors arising from a nevus sebaceous. PMID- 27194975 TI - Eccrine Poroma Arising within Nevus Sebaceous. AB - Nevus sebaceous is a congenital, benign hamartomatous lesion, characterized by a yellowish to skin-colored, hairless, verrucous plaque on the head and neck region. In later life, a secondary tumor, either benign or malignant, can develop within nevus sebaceous. Eccrine poroma developing on nevus sebaceous is extremely rare. There are few case reports of eccrine poroma developing within nevus sebaceous. We report a case of a 30-year-old female who presented with a congenital, hairless, verrucous, yellowish lesion on the scalp and an erythematous nodule arising within the yellowish lesion for 8 months. Her clinical presentation and histopathological findings were compatible with nevus sebaceous and eccrine poroma. PMID- 27194976 TI - A Second Case of Gobello Nevus Syndrome. AB - An uncommon type of epidermal nevus characterized by hyperpigmented hyperkeratotic bands following a Blaschko-linear pattern and generalized follicular hyperkeratosis were observed in a 17-year-old male patient who additionally showed tufted hair folliculitis on the scalp and clinodactyly of the fifth finger of both hands. The combination of epidermal nevus with skeletal abnormalities was first described by Gobello et al. [Dermatology 2000;201:51-55] as a new epidermal nevus syndrome that was named after the first author of this work. Our case shows identical clinical and histopathological features and represents the second case of this rare syndrome reported in the literature. PMID- 27194977 TI - Nilotinib-Induced Keratosis Pilaris. AB - Nilotinib is a second-generation Bcr-Abl tyrosine kinase inhibitor (TKI) that is approved for the treatment of imatinib-resistant chronic myeloid leukaemia expressing the Bcr-Abl mutation. Cutaneous adverse drug reactions occur more frequently in patients using this medication. We present a case of nilotinib induced keratosis pilaris that did not have accompanying symptoms of alopecia or pruritus. Greater recognition of this association is needed so that appropriate treatment can be instituted to ensure a good oncologic outcome. PMID- 27194978 TI - Intractable Postoperative Wounds Caused by Self-Inflicted Trauma in a Patient with Cutaneous Munchausen Syndrome Presenting as a Pyoderma Gangrenosum-Like Lesion. AB - A 50-year-old Japanese woman consulted the emergency department of our hospital for bleeding due to an intractable postoperative wound on the lower abdomen; the postoperative wound was owing to a laparoscopic cholecystectomy performed 1 year previously for acute cholecystitis. She presented with a painful ulcer on her right lower abdomen. She also presented with multiple scars, skin grafts on the extremities, and a missing left lower leg, the causes for all of which were unexplained. The results of her blood test were normal, except for the hemoglobin level. Histology of the skin biopsy specimen from the ulcer did not show any specific findings. The previous surgeon who had performed the laparoscopic cholecystectomy revealed that surgical wound dehiscence had occurred during her admission. After a body restraint had been applied, the ulcer improved. Medical records indicated that she had been admitted to the department of plastic surgery at our hospital for skin grafting of a leg ulcer. During that admission, she refused to consult with the department of psychiatry, al-though the staff suspected mental disorders. Therefore, we diagnosed her with cutaneous Munchausen syndrome. After vacuum-assisted closure (VAC) therapy had been performed to prevent her from traumatizing the ulcer again, it rapidly became granulated and reepithelialized. Munchausen syndrome is characterized by feigning physical symptoms to seek attention. Patients self-inflict numerous lesions, keep getting admitted to different hospitals, and feign acute illness, usually spectacular diseases. VAC therapy may be effective for preventing patients with cutaneous Munchausen syndrome from traumatizing their wounds. PMID- 27194979 TI - Transient Efficacy of Tofacitinib in Alopecia Areata Universalis. AB - Alopecia areata is a common autoimmune disorder that targets hair follicles. Swarms of lymphocytes surround the basis of the follicles, inducing loss of pigmented terminal hair and subsequently inhibit further hair growth. Depending on the extent of involvement, alopecia areata can be associated with a dramatic reduction of quality of life. Currently, no targeted treatment option is available, and topical immune therapies or immunosuppressive drugs are typically used with mixed success. Recently, several cases of alopecia areata responding to Janus kinase inhibitors were published. Here, we report on a businessman with alopecia areata universalis who was treated with tofacitinib. We observed initial signs of hair regrowth in the same timeframe as previously reported, but efficacy quickly waned again, leading to renewed effluvium. Thus, even though tofacitinib and ruxolitinib are a promising new treatment option, we have yet to learn more about their potential role in each particular patient's individual treatment strategy. PMID- 27194980 TI - Alectinib-Induced Alopecia in a Patient with Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer. AB - Alectinib, a novel alternative anaplastic lymphoma kinase (ALK) inhibitor, is highly effective against ALK-positive non-small cell lung cancer (NSCLC) and is well tolerated. Molecular targeted agents generally have little contribution to alopecia. We encountered a case of alopecia that developed gradually over 2 months after initiation of alectinib administration for the treatment of ALK positive NSCLC. The patient had no history of alopecia in previous treatments of cisplatin + pemetrexed and crizotinib. The present case indicates that alopecia should be taken into consideration as toxicity during alectinib treatment, which could adversely affect the psychological and emotional condition and quality of life even in patients treated with specific molecular targeted agents. PMID- 27194981 TI - Urachal Carcinoma with Choroidal, Lung, Lymph Node, Adrenal, Mammary, and Bone Metastases and Peritoneal Carcinomatosis Showing Partial Response after Chemotherapy Treatment with a Modified Docetaxel, Cisplatin and 5-Fluorouracil Regimen. AB - Urachal carcinoma (UC) is a rare tumor mainly affecting middle-aged males. Metastases occur most frequently in lymph nodes and the lungs. There are no standard adjuvant and metastatic treatments. We report the case of a 36-year-old female with UC treated with partial cystectomy who relapsed 3 years after surgery with left choroidal, lung, mediastinal lymph node, right adrenal, mammary, and bone metastases as well as peritoneal carcinomatosis. She obtained a partial response after 10 cycles of chemotherapy with a modified docetaxel, cisplatin and 5-fluorouracil (mTPF) regimen. This is the first report on the use of the mTPF regimen in UC and on the existence of choroidal, adrenal, and mammary metastases. PMID- 27194982 TI - A Case of Hypophosphatemia with Increased Urinary Excretion of Phosphorus Associated with Ibrutinib. AB - Ibrutinib, an irreversible oral inhibitor of Bruton's tyrosine kinase, has been used in the treatment of patients with multiple hematologic malignancies. A 59 year-old male with chronic lymphocytic leukemia was treated with 420 mg/day of ibrutinib. No evidence of bruising or diarrhea was noted. The treatment was complicated by a transient increase in creatinine (from a baseline of 1.2 to 1.5 mg/dl) and potassium (reaching a peak of 6.5 mEq/l). Uric acid and calcium levels were normal. The patient developed hypophosphatemia (prior to initiation of therapy the serum phosphorus was 2.9 mg/dl). No metabolic acidosis was noted. Urinalysis showed no glucosuria or proteinuria. Urinary fraction of excretion of phosphate was found to be 345% (normal <5%). Because of these changes, ibrutinib was held, and the patient was given kayexalate. Serum potassium normalized. Serum phosphorus was checked a couple of weeks later and also normalized. A lower dose of ibrutinib (140 mg/day) was restarted. Upon follow-up, the phosphorus level has been between 2.9 and 3.2 mg/dl. No further evidence of hyperkalemia has been noted. Renal function has remained at baseline. To the best of our knowledge, this is the first case report describing the mechanism of hypophosphatemia in a patient treated with ibrutinib. PMID- 27194983 TI - Gastric Schwannoma Mimicking Malignant Gastrointestinal Stromal Tumor Exhibiting Increased Fluorodeoxyglucose Uptake. AB - A schwannoma is a kind of neurogenic tumor that rarely occurs in the gastrointestinal tract. Gastric schwannomas make up 0.2% of all gastric neoplasms. Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors and up to 60-70% of GIST occur in the stomach. Schwannoma and GIST are similar in clinical features, so they are difficult to differentiate preoperatively. Differential diagnosis of these two submucosal tumors is important because of the malignant potential of GIST and the relatively benign course of gastric schwannomas. We report a 49-year-old woman who was diagnosed after operation with a gastric schwannoma, which was suspected a malignant GIST by fluorine-18-fluorodeoxyglucose positron emission computed tomography imaging. PMID- 27194984 TI - Epidermal Cyst in the Scrotum Successfully Treated while Preserving the Testis: A Case Report. AB - A 66-year-old male was referred to our hospital for further examination of a scrotal mass. Because of the risk of testicular cancer, we first clamped the vessels as a course of higher orchiectomy. Then, we approached the tumor through the scrotum and successfully resected it while preserving the testis. A histopathological diagnosis revealed an epidermal cyst. We herein report a rare case of an intrascrotal epidermal cyst successfully treated while preserving the testis. PMID- 27194985 TI - BRAF Mutation (V600E) Prevalence in Mexican Patients Diagnosed with Melanoma. AB - BACKGROUND: B-Raf is a serine/threonine protein kinase activating the MAP kinase/ERK-signaling pathway. It has been shown that 50% of melanomas harbor activating BRAF mutations, with over 90% being the V600E mutation. OBJECTIVE: The goal of this research was to determine the prevalence of the BRAF V600E mutation in patients from Central Mexico diagnosed with primary melanoma. METHODS: Skin biopsies from 47 patients with melanoma were obtained from the dermatology department of the Hospital General 'Dr. Manuel Gea Gonzalez' in Mexico City. For BRAF mutation determination, after DNA isolation, the gene region where the mutation occurs was amplified by PCR. Subsequently, the presence or absence of the V600E mutation was detected by Sanger sequencing performed at the private molecular diagnostic laboratory Vitagenesis in Monterrey, Mexico. RESULTS: Of the 47 patients sampled, 6.4% harbored the V600E mutation. No statistical significance was found between mutations and the type of tumor. PMID- 27194986 TI - Increased Intracranial Pressure in a Boy with Gorham-Stout Disease. AB - Gorham-Stout disease (GSD), also known as vanishing bone disease, is a rare disorder, which most commonly presents in children and young adults and is characterized by an excessive proliferation of lymphangiomatous tissue within the bones. This lymphangiomatous proliferation often affects the cranium and, due to the proximate location to the dura surrounding cerebrospinal fluid (CSF) spaces, can result in CSF leaks manifesting as intracranial hypotension with clinical symptoms to include orthostatic headache, nausea, and vertigo. We present the case of a boy with GSD and a known history of migraine headaches who presented with persistent headaches due to increased intracranial pressure. Although migraine had initially been suspected, he was eventually diagnosed with intracranial hypertension after developing ophthalmoplegia and papilledema. We describe the first known instance of successful medical treatment of increased intracranial pressure in a patient with GSD. PMID- 27194987 TI - Simultaneous Spinal and Intracranial Chronic Subdural Hematoma Cured by Craniotomy and Laminectomy: A Video Case Report. AB - Simultaneous spinal and intracranial chronic subdural hematoma (CSDH) is a rare entity. A 67-year-old man visited our hospital due to headache after diving into a river 2 weeks before. Non-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) revealed bilateral intracranial CSDH. The bilateral CSDH was evacuated and his symptoms improved. Three days after craniotomy, he complained of sensory disturbance on his buttocks. Lumbar MRI showed a space occupying lesion behind the thecal sac at L5. CT with myelography showed a subdural mass lesion; there was no communication with the subarachnoid space. Fourteen days after craniotomy, L5 laminectomy was performed and the dura mater was incised carefully. The video shows that a liquid hematoma similar to the intracranial CSDH flowed out, followed by cerebrospinal fluid. His symptoms improved after the operation and the hematoma did not recur. This is a rare condition of spinal CSDH demonstrated by neuroimaging and intraoperative video. PMID- 27194988 TI - A Dextral Primary Progressive Aphasia Patient with Right Dominant Hypometabolism and Tau Accumulation and Left Dominant Amyloid Accumulation. AB - BACKGROUND: Primary progressive aphasia (PPA) is a degenerative disease that presents as progressive decline of language ability with preservation of other cognitive functions in the early stages. Three subtypes of PPA are known: progressive nonfluent aphasia, semantic dementia, and logopenic aphasia (LPA). PATIENTS AND METHODS: We report the case of a 77-year-old patient with PPA whose clinical findings did not correspond to the three subtypes but mainly fit LPA. Unlike other LPA patients, however, this patient showed a right hemisphere predominant glucose hypometabolism and tau accumulation and a left hemisphere predominant amyloid deposition. The right-handed patient presented with comprehension difficulty followed by problems naming familiar objects. This isolated language problem had deteriorated rapidly for 2 years, followed by memory difficulties and impairment of daily activities. Using a Korean version of the Western Aphasia Battery, aphasia was consistent with a severe form of Wernicke's aphasia. According to the brain magnetic resonance imaging and (18)F fludeoxyglucose positron emission tomography results, right hemisphere atrophy and hypometabolism, more predominant on the right hemisphere than the left, were apparent despite the fact that Edinburgh Handedness Questionnaire scores indicated strong right-handedness. On Pittsburgh compound B-PET, amyloid accumulation was asymmetrical with the left hemisphere being more predominant than the right, whereas (18)F-T807-PET showed a right dominant tau accumulation. CONCLUSIONS: This is the first report of atypical PPA, in which the patient exhibited crossed aphasia and asymmetrical amyloid accumulation. PMID- 27194989 TI - Acute Retinal Necrosis Associated with Epstein-Barr Virus in a Patient Undergoing Immunosuppressive Therapy. AB - Acute retinal necrosis (ARN) is a rapidly progressive and severe retinitis resulting in a poor visual outcome. Infections caused by herpes viruses such as herpes simplex virus (HSV) types 1 and 2 or the varicella zoster virus (VZV) are known to be implicated in the development of ARN. In the present study, an 80 year-old female with ARN was examined. She had been affected with rheumatoid arthritis and had taken methotrexate for over 10 years. Her right eye showed clinical features of ARN, and her left eye showed mild retinitis. The genomic DNA in the aqueous humor and vitreous fluid from her right eye were analyzed by a comprehensive polymerase chain reaction (PCR) assay to screen infectious pathogens including viruses. The Epstein-Barr virus (EBV) was detected from both specimens, but neither HSV or VZV nor cytomegalovirus was detected. She underwent intraocular surgery following systemic corticosteroid and acyclovir applications. However, although the retinitis of her right eye was extinguished, the final visual outcome was blindness due to optic nerve atrophy. There are few reports indicating that EBV is associated with ARN development. The present findings suggest that EBV alone can be the causative agent of ARN. PMID- 27194990 TI - Two Patients with Dry Eye Disease Followed Up Using an Expression Assay of Ocular Surface Mucin. AB - PURPOSE: We report 2 patients with dry eye disease followed up using the expression levels of ocular surface mucin. CASE REPORTS: Patient 1: a 57-year-old woman with Sjogren's syndrome-associated dry eyes experienced severe dryness and foreign body sensation in both her eyes, and instilled sodium hyaluronate ophthalmic solution 0.3% about 10-15 times daily. We measured the expression levels of MUC5AC mRNA (MUC5AC) and MUC16 mRNA (MUC16) by using real-time reversed transcription polymerase chain reaction for the specimens of modified impression cytology. Expression levels of MUC5AC and MUC16 on her ocular surface were very low. Subjective symptoms and expression levels of ocular surface mucin improved after combined treatment of rebamipide (4 times daily) and fluorometholone (once daily) ophthalmic suspension. Patient 2: a 62-year-old man with chronic graft versus-host disease-associated dry eye experienced severe foreign body sensation and developed superficial punctate keratopathy with mucous thread and filamentary keratitis. Expression level of MUC5AC was very high at baseline. Subjective symptoms and expression levels of ocular surface mucin improved by combined treatment of rebamipide (4 times daily) and fluorometholone (once daily) ophthalmic suspension. CONCLUSION: Clinical test for MUC gene expression on the ocular surface was found to be useful in the follow-up of dry eye treatment. PMID- 27194991 TI - Serum Cortisol-to-Cortisone Ratio and Blood Pressure in Severe Obesity before and after Weight Loss. AB - BACKGROUND/AIMS: The pathogenesis of obesity-associated hypertension is poorly understood. Serum cortisol-to-cortisone ratio (F/E ratio) is a marker of cortisol metabolism. Our objective was to determine whether the serum F/E ratio is associated with blood pressure (BP) in patients after significant weight loss (>=15% from baseline weight). METHODS: Sera from 43 nondiabetic, severely obese males participating in a weight management program were assayed for F and E by mass spectrometry. We assessed whether changes in the F/E ratio accompanying weight loss correlate with changes in the systolic (SBP) and diastolic BP (DBP). Linear regression was used to evaluate change in the F/E ratio as a predictor of change in BP. RESULTS: The body mass index decreased from 40.8 +/- 5.6 to 33.7 +/ 4.8 (p < 0.001); also, SBP (133.2 +/- 13.8 vs. 124.1 +/- 14.3 mm Hg; p < 0.001) and DBP (69.8 +/- 8.0 vs. 66.6 +/- 9.4 mm Hg; p = 0.026) decreased during the study. The baseline F/E ratio tended to associate with baseline DBP (Spearman's r = -0.29, p = 0.06), and change in the serum F/E ratio correlated with change in DBP (Spearman's r = -0.32, p = 0.036). Change in the F/E ratio also tended to associate with change in SBP (Spearman's r = -0.27, p = 0.08). A multiple linear regression model adjusted for change in the F/E ratio and age explained 22% of the variance in SBP change (R(2) = 0.22, p = 0.007). Change in the F/E ratio independently predicted change in SBP (p = 0.036). CONCLUSION: In our sample of nondiabetic, severely obese males, change in the serum F/E ratio was associated with change in BP after weight loss. PMID- 27194992 TI - Clinical Practice of Two Measurements of Home Blood Pressure on Each Occasion in Patients with Chronic Kidney Disease. AB - BACKGROUND/AIMS: Although several guidelines propose two or three measurements of home blood pressure (HBP) on each occasion, the actual status of multiple measurements is not clear in the practical management of hypertension. We surveyed the details regarding two measurements of HBP in patients with chronic kidney disease (CKD). METHODS: HBP was measured twice every morning and evening over 7 consecutive days in 175 CKD patients. The distribution of the differences between two BP values (2nd - 1st BP) and their association with BP parameters were evaluated. RESULTS: The 2nd - 1st morning systolic BP (SBP) and diastolic BP (DBP) differences were -2.3 +/- 4.1 and -0.4 +/- 2.6 mm Hg, respectively. The proportion of 2nd - 1st morning SBP differences >0 mm Hg was 31.7% in a total of 1,195 measurements. Eighty patients (45.7%) had days with a difference <=-5 mm Hg and days with a difference >=5 mm Hg in morning SBP during 7 days. The multivariate regression analysis of the SD values of 2nd - 1st morning SBP as a dependent variable showed that the SD value of the 1st morning SBP (beta = 0.65, p < 0.001) was a significant determinant. CONCLUSION: Although the 2nd SBP was 2 3 mm Hg lower than the 1st SBP in the population as a whole, various differences were found for each subject during 7 days. 2nd - 1st BP variability might be associated with day-by-day 1st BP variability. PMID- 27194993 TI - Assessing the Relationship of Angiotensin II Type 1 Receptors with Erythropoietin in a Human Model of Endogenous Angiotensin II Type 1 Receptor Antagonism. AB - HYPOTHESIS/INTRODUCTION: Angiotensin II (Ang II) has been shown to control erythropoietin (EPO) synthesis as Ang II type 1 receptor (AT1R) blockers block Ang-II-induced EPO oversecretion. To further explore the involvement of AT1R in processes controlling EPO levels, plasma EPO and mononuclear cell NADPH oxidase 4 (NOX4) - a NOX family member involved in oxygen sensing, which is a process central to controlling EPO levels - were assessed in Bartter's/Gitelman's syndrome (BS/GS) patients, a human model of endogenous AT1R antagonism and healthy subjects. Heme oxygenase (HO)-1, antioxidant and anti-inflammatory factor related to NOX4 activation, and the relationship of EPO and NOX4 to HO-1 were also assessed. MATERIALS AND METHODS: EPO was measured by chemiluminescent immunoassay, HO-1 by sandwich immunoassay and NOX4 protein expression by Western blot. RESULTS: EPO was increased in BS/GS patients compared to healthy subjects (7.64 +/- 2.47 vs. 5.23 +/- 1.07 U/l; p = 0.025), whereas NOX4 did not differ between BS/GS and healthy subjects (1.76 +/- 0.61 vs. 1.65 +/- 0.54 densitometric units; p = n.s.), and HO-1 was increased in BS/GS patients compared to healthy subjects (9.58 +/- 3.07 vs. 5.49 +/- 1.04 ng/ml; p = 0.003). NOX4 positively correlated with HO-1 only in BS/GS patients; no correlation was found between EPO and either NOX4 or HO-1 in those two groups. CONCLUSIONS: The effect of the renin angiotensin system on EPO cannot be solely mediated by Ang II via AT1R signaling, but rather, EPO levels are also determined by a complex interrelated set of signals that involve AT2R, nitric oxide levels, NOX4 and HO-1 activity. PMID- 27194994 TI - Renalase and Biomarkers of Contrast-Induced Acute Kidney Injury. AB - BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) remains one of the crucial issues related to the development of invasive cardiology. The massive use of contrast media exposes patients to a great risk of contrast-induced nephropathy and chronic kidney disease development, and increases morbidity and mortality rates. The serum creatinine concentration does not allow for a timely and accurate CI-AKI diagnosis; hence numerous other biomarkers of renal injury have been proposed. Renalase, a novel catecholamine-metabolizing amine oxidase, is synthesized mainly in proximal tubular cells and secreted into urine and blood. It is primarily engaged in the degradation of circulating catecholamines. Notwithstanding its key role in blood pressure regulation, renalase remains a potential CI-AKI biomarker, which was shown to be markedly downregulated in the aftermath of renal injury. In this sense, renalase appears to be the first CI-AKI marker revealing an actual loss of renal function and indicating disease severity. SUMMARY: The purpose of this review is to summarize the contemporary knowledge about the application of novel biomarkers of CI-AKI and to highlight the potential role of renalase as a functional marker of contrast-induced renal injury. KEY MESSAGES: Renalase may constitute a missing biochemical link in the mutual interplay between kidney and cardiac pathology known as the cardiorenal syndrome. PMID- 27194996 TI - Extracorporeal Membrane Oxygenation and the Kidney. AB - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is an effective therapy for patients with reversible cardiac and/or respiratory failure. Acute kidney injury (AKI) often occurs in patients supported with ECMO; it frequently evolves into chronic kidney damage or end-stage renal disease and is associated with a reported 4-fold increase in mortality rate. Although AKI is generally due to the hemodynamic alterations associated with the baseline disease, ECMO itself may contribute to maintaining kidney dysfunction through several mechanisms. SUMMARY: AKI may be related to conditions derived from or associated with extracorporeal therapy, leading to a reduction in renal oxygen delivery and/or to inflammatory damage. In particular, during pathological conditions requiring ECMO, the biological defense mechanisms maintaining central perfusion by a reduction of perfusion to peripheral organs (such as the kidney) have been identified as pretreatment and patient-related risk factors for AKI. Hormonal pathways are also impaired in patients supported with ECMO, leading to failures in mechanisms of renal homeostasis and worsening fluid overload. Finally, inflammatory damage, due to the primary disease, heart and lung crosstalk with the kidney or associated with extracorporeal therapy itself, may further increase the susceptibility to AKI. Renal replacement therapy can be integrated into the main extracorporeal circuit during ECMO to provide for optimal fluid management and removal of inflammatory mediators. KEY MESSAGES: AKI is frequently observed in patients supported with ECMO. The pathophysiology of the associated AKI is chiefly related to a reduction in renal oxygen delivery and/or to inflammatory damage. Risk factors for AKI are associated with a patient's underlying disease and ECMO related conditions. PMID- 27194995 TI - Association of Body Mass Index with Clinical Outcomes in Non-Dialysis-Dependent Chronic Kidney Disease: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Previous studies have not shown a consistent link between body mass index (BMI) and outcomes such as mortality and kidney disease progression in non dialysis-dependent chronic kidney disease (CKD) patients. Therefore, we aimed to complete a systematic review and meta-analysis study on this subject. METHODS: We searched MEDLINE, EMBASE, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Cochrane Central Register of Controlled Trials (CENTRAL), and screened 7,123 retrieved studies for inclusion. Two investigators independently selected the studies using predefined criteria and assessed each study's quality using the Newcastle-Ottawa quality assessment scale. We meta analyzed the results based on the BMI classification system by the WHO. RESULTS: We included 10 studies (with a total sample size of 484,906) in the systematic review and 4 studies in the meta-analyses. The study results were generally heterogeneous. However, following reanalysis of the largest reported study and our meta-analyses, we observed that in stage 3-5 CKD, being underweight was associated with a higher risk of death while being overweight or obese class I was associated with a lower risk of death; however, obesity classes II and III were not associated with risk of death. In addition, reanalysis of the largest available study showed that a higher BMI was associated with an incrementally higher risk of kidney disease progression; however, this association was attenuated in our pooled results. For earlier stages of CKD, we could not complete meta-analyses as the studies were sparse and had heterogeneous BMI classifications and/or referent BMI groups. CONCLUSION: Among the group of patients with stage 3-5 CKD, we found a differential association between obesity classes I-III and mortality compared to the general population, indicating an obesity paradox in the CKD population. PMID- 27194998 TI - Elevated Fibroblast Growth Factor 23 Concentration: Prediction of Mortality among Chronic Kidney Disease Patients. AB - BACKGROUND: The osteocyte-derived hormone, fibroblast growth factor 23 (FGF23), regulates the phosphorus metabolism and suppresses 1,25-dihydroxyvitamin D production, thereby mitigating hyperphosphatemia in patients with renal disorders. An elevated FGF23 level is suggested to be an early biomarker of altered phosphorus metabolism in the initial stages of chronic kidney disease (CKD) and acts as a strong predictor of mortality in dialysis patients. In the Saudi population, there is no report on the FGF23 level in CKD patients to date. This study aims to estimate the plasma FGF23 levels in the Saudi population and to correlate it with its clinical manifestations in order to ascertain its role in the pathogenesis of CKD patients. METHODS: The FGF23 level in the plasma samples was determined using ELISA in a diverse cohort of 89 cases with stage 3-5 CKD and 100 healthy subjects. The plasma FGF23 level was correlated with other biochemical parameters. RESULTS: The results revealed that the FGF23 level was markedly elevated among CKD patients compared to the control group, and a significant inverse correlation was observed between the FGF23 level and glomerular filtration rate. FGF23 elevation was approximately 40-fold among stage 5 patients compared to the control, while the elevation of phosphate, parathyroid hormone (PTH) and alkaline phosphatase was 2-, 3- and 8-fold in this stage, respectively. CONCLUSION: Elevated FGF23 levels may have a strong correlation with the disease pathogenesis. In addition, FGF23 might be a future therapeutic target to intervene against the progression of CKD as well as to increase patient survivability. PMID- 27194997 TI - The Role of Congestion in Cardiorenal Syndrome Type 2: New Pathophysiological Insights into an Experimental Model of Heart Failure. AB - BACKGROUND: In cardiorenal syndrome type 2 (CRS2), the role of systemic congestion in heart failure (HF) is still obscure. We studied a model of CRS2 [monocrotaline (MCT)-treated rats] secondary to pulmonary hypertension and right ventricular (RV) failure in order to evaluate the contribution of prevalent congestion to the development of kidney injury. METHODS: Ten animals were treated with MCT for 4 weeks until they developed HF. Eleven animals were taken as controls. Signs of hypertrophy and dilatation of the right ventricle demonstrated the occurrence of HF. Brain natriuretic peptide (BNP), serum creatinine (sCreatinine), both kidney and heart neutrophil gelatinase-associated lipocalin (NGAL), matrix metallopeptidase 9 (MMP9), serum cytokines as well as kidney and heart cell death, as assessed by TUNEL, were studied. RESULTS: Rats with HF showed higher BNP levels [chronic HF (CHF) 4.8 +/- 0.5 ng/ml; controls 1.5 +/- 0.2 ng/ml; p < 0.0001], marked RV hypertrophy and dilatation (RV mass/RV volume: CHF 1.46 +/- 0.31, controls 2.41 +/- 0.81; p < 0.01) as well as pleural and peritoneal effusions. A significant increase in proinflammatory cytokines and sCreatinine was observed (CHF 3.06 +/- 1.3 pg/ml vs. controls 0.54 +/- 0.23 pg/ml; p = 0.04). Serum (CHF 562.7 +/- 93.34 ng/ml vs. controls 245.3 +/- 58.19 ng/ml; p = 0.02) as well as renal and heart tissue NGAL levels [CHF 70,680 +/- 4,337 arbitrary units (AU) vs. controls 32,120 +/- 4,961 AU; p = 0.001] rose significantly, and they were found to be complexed with MMP9 in CHF rats. A higher number of kidney TUNEL-positive tubular cells was also detected (CHF 114.01 +/- 45.93 vs. controls 16.36 +/- 11.60 cells/mm(2); p = 0.0004). CONCLUSION: In this model of CHF with prevalent congestion, kidney injury is characterized by tubular damage and systemic inflammation. The upregulated NGAL complexed with MMP9 perpetuates the vicious circle of kidney/heart damage by enhancing the enzymatic activity of MMP9 with extracellular matrix degradation, worsening heart remodeling. PMID- 27194999 TI - Screening for Language Disorders in Stroke: German Validation of the Language Screening Test (LAST). AB - BACKGROUND: Screening of aphasia in acute stroke is crucial for directing patients to early language therapy. The Language Screening Test (LAST), originally developed in French, is a validated language screening test that allows detection of a language deficit within a few minutes. The aim of the present study was to develop and validate two parallel German versions of the LAST. METHODS: The LAST includes subtests for naming, repetition, automatic speech, and comprehension. For the translation into German, task constructs and psycholinguistic criteria for item selection were identical to the French LAST. A cohort of 101 stroke patients were tested, all of whom were native German speakers. Validation of the LAST was based on (1) analysis of equivalence of the German versions, which was established by administering both versions successively in a subset of patients, (2) internal validity by means of internal consistency analysis, and (3) external validity by comparison with the short version of the Token Test in another subset of patients. RESULTS: The two German versions were equivalent as demonstrated by a high intraclass correlation coefficient of 0.91. Furthermore, an acceptable internal structure of the LAST was found (Cronbach's alpha = 0.74). A highly significant correlation (r = 0.74, p < 0.0001) between the LAST and the short version of the Token Test indicated good external validity of the scale. CONCLUSION: The German version of the LAST, available in two parallel versions, is a new and valid language screening test in stroke. PMID- 27195000 TI - Comparison between Early-Onset and Late-Onset Alzheimer's Disease Patients with Amnestic Presentation: CSF and (18)F-FDG PET Study. AB - BACKGROUND/AIMS: To investigate the differences in brain glucose consumption between patients with early onset of Alzheimer's disease (EOAD, aged <=65 years) and patients with late onset of Alzheimer's disease (LOAD, aged >65 years). METHODS: Differences in brain glucose consumption between the groups have been evaluated by means of Statistical Parametric Mapping version 8, with the use of age, sex, Mini-Mental State Examination and cerebrospinal fluid values of ABeta1 42, phosphorylated Tau and total Tau as covariates in the comparison between EOAD and LOAD. RESULTS: As compared to LOAD, EOAD patients showed a significant decrease in glucose consumption in a wide portion of the left parietal lobe (BA7, BA31 and BA40). No significant differences were obtained when subtracting the EOAD from the LOAD group. CONCLUSIONS: The results of our study show that patients with EOAD show a different metabolic pattern as compared to those with LOAD that mainly involves the left parietal lobe. PMID- 27195001 TI - Brain Perfusion in Corticobasal Syndrome with Progressive Aphasia. AB - BACKGROUND: Brain perfusion may differ between patients with corticobasal syndrome (CBS) with and without aphasia. METHODS: Twenty-six (9 males and 17 females; mean age 76 +/- 5.3 years) patients with CBS were enrolled in the study. Brain MRI and single-photon emission computed tomography were performed in all subjects. Language was evaluated using the Standard Language Test of Aphasia. The patients were divided into two subgroups according to the presence or absence of progressive aphasia. Differences in the regional cerebral blood flow (rCBF) between the two groups were detected based on voxel-by-voxel group analysis using Statistical Parametric Mapping 8. RESULTS: All patients exhibited asymmetric motor symptoms and signs, including limb apraxia, bradykinesia, and akinetic rigidity. Of 26 patients, 9 had a clinically obvious language disturbance, characterized as nonfluent aphasia. Almost all CBS patients with aphasia exhibited cortical atrophy predominantly in the left frontal and temporal lobes with widening of the Sylvian fissure on MRI. The rCBF in the left middle frontal gyrus differed significantly between CBS patients with and without aphasia. CONCLUSION: CBS patients with aphasia exhibit motor symptoms predominantly on the right side and cortical atrophy mainly in the left perisylvian cortices. In particular, left frontal dysfunction might be related to nonfluent aphasia in CBS. PMID- 27195002 TI - Cerebrospinal Fluid TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis Patients with and without the C9ORF72 Hexanucleotide Expansion. AB - BACKGROUND: TDP-43 is the main protein component of ubiquitinated inclusions in a subgroup of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) patients. The C9ORF72 hexanucleotide expansion is one of the main mutations associated with TDP-43 pathology in FTLD and ALS. Our aim was to analyze cerebrospinal fluid (CSF) TDP-43 levels and Alzheimer's disease biomarkers in FTLD and ALS patients and to test whether the C9ORF72 expansion carrier status affects these variables. METHODS: The patient cohort consisted of 90 clinically well-characterized FTLD (n = 69) and ALS (n = 21) patients. There were 30 patients with the C9ORF72 expansion and 60 patients without the expansion. CSF TDP-43, ABeta1-42, t-tau, and phospho-tau levels were measured using commercial ELISA kits. RESULTS: There was no difference in CSF TDP-43 levels between the C9ORF72 expansion carriers and the noncarriers. CSF TDP-43 levels were higher in ALS patients than in FTLD patients, and this finding was independent of the C9ORF72 expansion carrier status. Males had significantly higher TDP-43 levels than females (p = 0.008 in the total cohort). CONCLUSION: CSF TDP-43 does not seem to distinguish the C9ORF72 expansion carriers from noncarriers. However, higher CSF TDP-43 levels were detected in ALS than in FTLD, which might be an indicator of a more rapid progression of TDP-43 pathology in ALS. PMID- 27195003 TI - Polychromatic Iterative Statistical Material Image Reconstruction for Photon Counting Computed Tomography. AB - This work proposes a dedicated statistical algorithm to perform a direct reconstruction of material-decomposed images from data acquired with photon counting detectors (PCDs) in computed tomography. It is based on local approximations (surrogates) of the negative logarithmic Poisson probability function. Exploiting the convexity of this function allows for parallel updates of all image pixels. Parallel updates can compensate for the rather slow convergence that is intrinsic to statistical algorithms. We investigate the accuracy of the algorithm for ideal photon-counting detectors. Complementarily, we apply the algorithm to simulation data of a realistic PCD with its spectral resolution limited by K-escape, charge sharing, and pulse-pileup. For data from both an ideal and realistic PCD, the proposed algorithm is able to correct beam hardening artifacts and quantitatively determine the material fractions of the chosen basis materials. Via regularization we were able to achieve a reduction of image noise for the realistic PCD that is up to 90% lower compared to material images form a linear, image-based material decomposition using FBP images. Additionally, we find a dependence of the algorithms convergence speed on the threshold selection within the PCD. PMID- 27195004 TI - Online Knowledge-Based Model for Big Data Topic Extraction. AB - Lifelong machine learning (LML) models learn with experience maintaining a knowledge-base, without user intervention. Unlike traditional single-domain models they can easily scale up to explore big data. The existing LML models have high data dependency, consume more resources, and do not support streaming data. This paper proposes online LML model (OAMC) to support streaming data with reduced data dependency. With engineering the knowledge-base and introducing new knowledge features the learning pattern of the model is improved for data arriving in pieces. OAMC improves accuracy as topic coherence by 7% for streaming data while reducing the processing cost to half. PMID- 27195005 TI - Planning the City Logistics Terminal Location by Applying the Green p-Median Model and Type-2 Neurofuzzy Network. AB - The paper herein presents green p-median problem (GMP) which uses the adaptive type-2 neural network for the processing of environmental and sociological parameters including costs of logistics operators and demonstrates the influence of these parameters on planning the location for the city logistics terminal (CLT) within the discrete network. CLT shows direct effects on increment of traffic volume especially in urban areas, which further results in negative environmental effects such as air pollution and noise as well as increased number of urban populations suffering from bronchitis, asthma, and similar respiratory infections. By applying the green p-median model (GMM), negative effects on environment and health in urban areas caused by delivery vehicles may be reduced to minimum. This model creates real possibilities for making the proper investment decisions so as profitable investments may be realized in the field of transport infrastructure. The paper herein also includes testing of GMM in real conditions on four CLT locations in Belgrade City zone. PMID- 27195006 TI - Clinicopathologic Significance of Extranodal Tumor Extension in Colorectal Adenocarcinoma with Regional Lymph Node Metastasis. AB - Background. This study investigated the clinicopathologic significance of extranodal tumor extension in colorectal adenocarcinoma with lymph node metastasis. Method. Included were 419 patients who underwent curative resection for primary colorectal adenocarcinoma. Results. Extranodal tumor extension was observed more frequently in tumors with ulceroinfiltrative gross type (p = 0.026), higher histologic grade (p = 0.012), high grade tumor budding (p = 0.003), vascular invasion (p < 0.001), perineural invasion (p = 0.015), tumor deposit (p < 0.001), high ratio of metastatic/total lymph nodes (p < 0.001), and high pN stage (p < 0.001). Overall survival was significantly different between an extranodal tumor extension (-) group and an extranodal tumor extension (+) group for both N1 (p = 0.022) and N2 homogeneous staging (p = 0.007). Both overall (p = 0.002) and disease-free survival (p = 0.001) were significantly different between the two groups in an N1a homogeneous group and overall survival was significantly different (p = 0.016) in an N2b homogeneous group. Conclusion. Our study demonstrated that extranodal tumor extension was a useful prognostic factor for colorectal adenocarcinoma with lymph node metastasis, especially in homogeneous pN staging groups. PMID- 27195007 TI - Do Aging and Tactile Noise Stimulation Affect Responses to Support Surface Translations in Healthy Adults? AB - Appropriate neuromuscular responses to support surface perturbations are crucial to prevent falls, but aging-related anatomical and physiological changes affect the appropriateness and efficiency of such responses. Low-level noise application to sensory receptors has shown to be effective for postural improvement in a variety of different balance tasks, but it is unknown whether this intervention may have value for improvement of corrective postural responses. Ten healthy younger and ten healthy older adults were exposed to sudden backward translations of the support surface. Low-level noise (mechanical vibration) to the foot soles was added during random trials and temporal (response latency) and spatial characteristics (maximum center-of-pressure excursion and anterior-posterior path length) of postural responses were assessed. Mixed-model ANOVA was applied for analysis of postural response differences based on age and vibration condition. Age affected postural response characteristics, but older adults were well able to maintain balance when exposed to a postural perturbation. Low-level noise application did not affect any postural outcomes. Healthy aging affects some specific measures of postural stability, and in high-functioning older individuals, a low-level noise intervention may not be valuable. More research is needed to investigate if recurring fallers and neuropathy patients could benefit from the intervention in postural perturbation tasks. PMID- 27195008 TI - Consecutive Case Series of Healed Single-Molar Sites Immediately Restored with Wide-Diameter Implants: A 1-Year Evaluation. AB - Introduction. To evaluate outcomes of wide-diameter (6 mm) implants immediately provisionalized with cement-retained single crowns in posterior molar sites. Materials and Methods. Forty-eight consecutive patients received a total of 53 moderately rough-surface, 6 mm diameter implants in healed sites. All implants were immediately provisionalized with a cement-retained provisional crown. Final prosthesis with cement-retained porcelain fused to metal crowns was delivered 3-6 months later. Patients were followed up for 1 year. Outcome measures were implant failures and success rate, complications, marginal bone levels, bone level changes, papilla index, bleeding on probing, and inflammation. Results. One patient was lost to follow-up. At one year, the implant survival and success rate were 98.1%. The mean marginal bone loss after 1 year was -0.17 +/- 1.84 mm. Ideal papilla score was recorded at 83.8% of the sites. More than 95.6% of the sites showed no bleeding or inflammation. No procedure-related or device-related adverse events were reported. Conclusion. Wide-diameter (6 mm) implants can safely and successfully replace single posterior molars. Longer follow-up studies are necessary to evaluate the long-term success of these implants. PMID- 27195009 TI - Novel Microdilution Method to Assess Double and Triple Antibiotic Combination Therapy In Vitro. AB - An in vitro microdilution method was developed to assess double and triple combinations of antibiotics. Five antibiotics including ciprofloxacin, amikacin, ceftazidime, piperacillin, and imipenem were tested against 10 clinical isolates of Pseudomonas aeruginosa. Each isolate was tested against ten double and nine triple combinations of the antibiotics. A 96-well plate was used to test three antibiotics, each one alone and in double and triple combinations against each isolate. The minimum bacteriostatic and bactericidal concentrations in combination were determined with respect to the most potent antibiotic. An Interaction Code (IC) was generated for each combination, where a numerical value was designated based on the 2-fold increase or decrease in the MICs with respect to the most potent antibiotic. The results of the combinations were verified by time-kill assay at constant concentrations of the antibiotics and in a chemostat. Only 13% of the double combinations were synergistic, whereas 5% showed antagonism. Forty-three percent of the triple combinations were synergistic with no antagonism observed, and 100% synergism was observed in combination of ciprofloxacin, amikacin, and ceftazidime. The presented protocol is simple and fast and can help the clinicians in the early selection of the effective antibiotic therapy for treatment of severe infections. PMID- 27195010 TI - Therapeutic Roles of Tendon Stem/Progenitor Cells in Tendinopathy. AB - Tendinopathy is a tendon disorder characterized by activity-related pain, local edema, focal tenderness to palpation, and decreased strength in the affected area. Tendinopathy is prevalent in both athletes and the general population, highlighting the need to elucidate the pathogenesis of this disorder. Current treatments of tendinopathy are both conservative and symptomatic. The discovery of tendon stem/progenitor cells (TSPCs) and erroneous differentiation of TSPCs have provided new insights into the pathogenesis of tendinopathy. In this review, we firstly present the histopathological characteristics of tendinopathy and explore the cellular and molecular cues in the pathogenesis of tendinopathy. Current evidence of the depletion of the stem cell pool and altered TSPCs fate in the pathogenesis of tendinopathy has been presented. The potential regulatory factors for either tenogenic or nontenogenic differentiation of TSPCs are also summarized. The regulation of endogenous TSPCs or supplementation with exogenous TSPCs as therapeutic targets for the treatment of tendinopathy is proposed. Therefore, inhibiting the erroneous differentiation of TSPCs and regulating the differentiation of TSPCs into tendon cells might be important areas of future research and could provide new clinical treatments for tendinopathy. The current evidence suggests that TSPCs are promising therapeutic targets for the management of tendinopathy. PMID- 27195012 TI - Pattern of Hepatitis A Virus Epidemiology in Nursing Students and Adherence to Preventive Measures at Two Training Wards of a University Hospital. AB - BACKGROUND: Nursing students can be exposed to patients with hepatitis A virus (HAV) and can represent a vehicle of transmission both for health personnel, patients and relatives. OBJECTIVES: The aim of this study was to assess the risk of HAV infection in nursing students during their internship. PATIENTS AND METHODS: A seroprevalence survey on HAV infection was performed on nursing students at the Cagliari university-hospital, together with the assessment of the compliance to preventive measures to decrease the risk of infection during their internship. Blood specimens were obtained from 253 students. All serum samples were tested for anti-HAV antibodies (IgG) by the enzyme-linked immunosorbent assay (ELISA). Compliance to preventive measures was recorded by trained personnel. RESULTS: Overall HAV seropositivity in nursing students (mean age 24, range 17 - 45 years) was 3%. Compliance to preventive measures was not uniform (6% - 76%) and extremely low in some specific measures targeted to decrease the oral-fecal transmission. CONCLUSIONS: The high proportion of susceptible nursing students can contribute to an increase in the risk of nosocomial transmission, especially when specific preventive measures are not completely applied. Nursing education packages, before starting medical internship, should be implemented in order to increase their compliance to preventive measures, especially in wards at higher risk. Vaccination should be considered in wards at higher risk. PMID- 27195013 TI - A Novel Hydrodynamic Injection Mouse Model of HBV Genotype C for the Study of HBV Biology and the Anti-Viral Activity of Lamivudine. AB - BACKGROUND: Absence of an immunocompetent mouse model of persistent hepatitis B virus (HBV) infection has hindered the research of HBV infection and the development of antiviral medications. OBJECTIVES: In the present study, we aimed to develop a novel HBV genotype C mouse model by hydrodynamic injection (HI) and then used it to evaluate the antiviral activity of lamivudine. MATERIALS AND METHODS: A quantity of 15 MUg of HBV plasmid [pcDNA3.1 (+)-HBV1.3C], adeno associated virus-HBV1.3C (pAAV-HBV1.3C) or pAAV-HBV1.2A) were injected into male C57BL/6 mice, by HI, accounting for a total of 13 mice per group. Then, lamivudine was administered to mice with sustained HBV viremia, for 4 weeks. Real time polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry methods were used to detect HBsAg, HBeAg, HBsAb, HBcAg and HBV DNA, in serum or liver of the mice, at indicated time points. RESULTS: In 60% of the mice injected with pcDNA3.1 (+)-HBV1.3C, HBsAg, HBeAg, HBcAg and HBV DNA persisted for > 20 weeks in liver, post-injection, with no HBsAb appearance. Meanwhile, no significant inflammation was observed in these mice. Compared with pAAV-HBV1.2A and pAAV-HBV1.3C, pcDNA3.1 (+)-HBV1.3C administration led to higher and longer HBV viremia. Furthermore, serum HBV DNA was significantly reduced by lamivudine, after 4 weeks administration, and returned to the original level, after ceasing administration for 1 week, in the mice. CONCLUSIONS: In conclusion, our observations indicated that pcDNA3.1 (+) HBV1.3C was superior to AAV/HBV plasmid for establishment of persistent HBV infection by HI, in vivo, and this mouse model could be useful for studies of hepatitis virology and for the development of innovatory treatments for HBV infections. PMID- 27195014 TI - Exploratory, Phase II Controlled Trial of Shiunko Ointment Local Application Twice a Day for 4 Weeks in Ethiopian Patients with Localized Cutaneous Leishmaniasis. AB - The clinical efficacy and safety of Shiunko ointment (phase II clinical trial) was investigated in 40 Ethiopian patients with cutaneous leishmaniasis. Patients were randomized to receive treatment with Shiunko ointment or placebo (n = 20, each), applied on the lesion twice a day for 4 weeks. Clinicoparasitological assessments were performed before treatment, weekly for 4 weeks, and then 4, 8, and 12 weeks after the end of treatment. A marked reduction in lesion size was observed on week 16 of treatment in the Shiunko compared with placebo group (69% and 22% reduction, resp.). The overall rate of lesion reduction during the four weeks of treatment was significantly faster in the Shiunko group. Shiunko provided significant effect on wound closure in patients with ulcerated lesion. The clinical efficacy and tolerability of Shiunko were comparable to placebo with regard to its clinicoparasitological response (cure rate and parasitological clearance). Results of this preliminary study may suggest that Shiunko could be useful as adjuvant or as complementary treatment, not as alternatives to current treatment. Its attractive action includes fast lesion healing with a significantly smaller lesion at week 16 of treatment compared with placebo. In addition, its action was promoted in ulcerative lesions. PMID- 27195015 TI - Effect of Alkaloids Isolated from Phyllodium pulchellum on Monoamine Levels and Monoamine Oxidase Activity in Rat Brain. AB - Phyllodium pulchellum (P. pulchellum) is a folk medicine with a significant number of bioactivities. The aim of this study was to investigate the effects displayed by alkaloids fractions, isolated from the roots of P. pulchellum, on neurotransmitters monoamine levels and on monoamine oxidase (MAO) activity. Six alkaloids, which had indolealkylamine or beta-carboline skeleton, were obtained by chromatographic technologies and identified by spectroscopic methods such as NMR and MS. After treatment with alkaloids of P. pulchellum, the reduction of DA levels (54.55%) and 5-HT levels (35.01%) in rat brain was observed by HPLC-FLD. The effect of alkaloids on the monoamines metabolism was mainly related to MAO inhibition, characterized by IC50 values of 37.35 +/- 6.41 and 126.53 +/- 5.39 MUg/mL for MAO-A and MAO-B, respectively. The acute toxicity indicated that P. pulchellum extract was nontoxic. PMID- 27195016 TI - Modulatory Effect of Betulinic Acid on the Genotoxicity Induced by Different Mutagens in V79 Cells. AB - Betulinic acid (BA) is a pentacyclic triterpene that can be isolated from many medicinal plants around the world. The aim of this study was to evaluate the genotoxic potential of BA and its effect on the genotoxicity induced by different mutagens in V79 cells using the cytokinesis-block micronucleus assay. Different BA concentrations were combined with methyl methanesulfonate (MMS), doxorubicin (DXR), camptothecin (CPT), and etoposide (VP-16). The frequencies of micronuclei in cultures treated with different BA concentrations did not differ from those of the negative control. Treatment with BA and MMS resulted in lower micronucleus frequencies than those observed for cultures treated with MMS alone. On the other hand, a significant increase in micronucleus frequencies was observed in cultures treated with BA combined with DXR or VP-16 when compared to these mutagens alone. The results showed no effect of BA on CPT-induced genotoxicity. Therefore, BA was not genotoxic under the present experimental conditions and exerted a different influence on the genotoxicity induced by different mutagens. The modulatory effect of BA depends on the type of mutagen and concentrations used. PMID- 27195011 TI - Potential Therapies by Stem Cell-Derived Exosomes in CNS Diseases: Focusing on the Neurogenic Niche. AB - Neurodegenerative disorders are one of the leading causes of death and disability and one of the biggest burdens on health care systems. Novel approaches using various types of stem cells have been proposed to treat common neurodegenerative disorders such as Alzheimer's Disease, Parkinson's Disease, or stroke. Moreover, as the secretome of these cells appears to be of greater benefit compared to the cells themselves, the extracellular components responsible for its therapeutic benefit have been explored. Stem cells, as well as most cells, release extracellular vesicles such as exosomes, which are nanovesicles able to target specific cell types and thus to modify their function by delivering proteins, lipids, and nucleic acids. Exosomes have recently been tested in vivo and in vitro as therapeutic conveyors for the treatment of diseases. As such, they could be engineered to target specific populations of cells within the CNS. Considering the fact that many degenerative brain diseases have an impact on adult neurogenesis, we discuss how the modulation of the adult neurogenic niches may be a therapeutic target of stem cell-derived exosomes. These novel approaches should be examined in cellular and animal models to provide better, more effective, and specific therapeutic tools in the future. PMID- 27195017 TI - Elevated gamma-glutamyl transferase is associated with subclinical inflammation independent of cardiometabolic risk factors in an asymptomatic population: a cross-sectional study. AB - BACKGROUND: Serum Gamma-Glutamyl Transferase (GGT), a marker of oxidative stress, has been suggested to be independently associated with cardiovascular disease (CVD) events. We examined the association of serum GGT levels with the burden of subclinical inflammation across a spectrum of metabolic conditions. METHODS: We evaluated 5,446 asymptomatic subjects (43 +/- 10 years, 78 % males) who had an employer-sponsored physical between 2008 and 2010. Highly sensitivity C-reactive protein (hsCRP) was measured as a marker of underlying systemic inflammation. A linear regression of GGT quartiles with log transformed hsCRP and a multivariate logistic regression of GGT quartiles with elevated hsCRP (>=3 mg/L) were performed. RESULTS: Median GGT was 31 IU/l (IQR: 22-45 IU/l), 1025 (19 %) had hsCRP >= 3 mg/L. The median hsCRP increased with GGT quartiles (Q1: 0.9 mg/L, Q2: 1.1 mg/L, Q3: 1.4 mg/L, Q4: 1.6 mg/L, p < 0.001). Linear regression models showed GGT in the fourth quartile was associated with 0.45 mg/L (95 % CI 0.35, 0.54, p < 0.001) increase in log transformed hsCRP adjusting for risk factors. The Odds Ratio (OR) for an elevated hsCRP (>=3 mg/L) also increased with higher GGT quartiles; GGT Q2 1.44 (95 % CI 1.12, 1.85), GGT Q3 1.89 (95 % CI 1.45, 2.46), GGT Q4 2.22 (95 % CI 1.67, 2.95), compared to GGT Q1. The strength of association increased in the presence of and combination of metabolic conditions. CONCLUSION: In our cohort of asymptomatic individuals a higher serum GGT level was independently associated with increased burden of subclinical inflammation across metabolic states. These findings may explain GGT association with increased CVD risk. PMID- 27195018 TI - Frequency and Time Domain Analysis of Foetal Heart Rate Variability with Traditional Indexes: A Critical Survey. AB - Monitoring of foetal heart rate and its variability (FHRV) covers an important role in assessing health of foetus. Many analysis methods have been used to get quantitative measures of FHRV. FHRV has been studied in time and in frequency domain and interesting clinical results have been obtained. Nevertheless, a standardized definition of FHRV and a precise methodology to be used for its evaluation are lacking. We carried out a literature overview about both frequency domain analysis (FDA) and time domain analysis (TDA). Then, by using simulated FHR signals, we defined the methodology for FDA. Further, employing more than 400 real FHR signals, we analysed some of the most common indexes, Short Term Variability for TDA and power content of the spectrum bands and sympathovagal balance for FDA, and evaluated their ranges of values, which in many cases are a novelty. Finally, we verified the relationship between these indexes and two important parameters: week of gestation, indicator of foetal growth, and foetal state, classified as active or at rest. Our results indicate that, according to literature, it is necessary to standardize the procedure for FHRV evaluation and to consider week of gestation and foetal state before FHR analysis. PMID- 27195019 TI - Abducted children and youth in Lord's Resistance Army in Northeastern Democratic Republic of the Congo (DRC): mechanisms of indoctrination and control. AB - BACKGROUND: Globally, an estimated 300,000 children under the age of 18 participate in combat situations; those in armed groups in particular suffer prolonged exposure to psychological and physical abuse. The Lord's Resistance Army (LRA) is a rebel movement known for its widespread conscription of children; yet little is known about this process once the group moved beyond northern Uganda. In this paper, we describe the processes related to abduction and indoctrination of youth by the LRA in northeastern Democratic Republic of the Congo ( DRC). METHODS: In-depth interviews were conducted with formerly abducted children, their family members, community leaders, and service providers (total n = 34) in four communities in LRA-affected areas of northeastern DRC. Inductive coding of transcripts was undertaken to identify salient themes. RESULTS: Informants articulated a range of practices by the LRA to exert high levels of control over new recruits, including strict social isolation from recent abductees; control of communication; promoting new identity formation; and compelling children to act out strictly defined gendered roles. Witchcraft and secrecy are used to intimidate recruits and to magnify perception of the group's power. These methods promote de-identification with one's civilian and family life; and eventually the assimilation of a new language and identity. CONCLUSION: Indoctrination of newly abducted children into the LRA occurs via a complex system of control. This study provides one of the first detailed explorations of social and psychological mechanisms through which this is achieved, and focuses particularly on the gendered differences in the indoctrination process. Results support past findings that the LRA is a strategic and well-organized organization in its approach to enlisting child soldiers. Understanding some of the ways in which the LRA controls its recruits and the psychological impact of indoctrination enables reintegration programs to more effectively address these issues and serve the complex needs of formerly abducted children. PMID- 27195020 TI - The two Rasamsonia emersonii alpha-glucuronidases, ReGH67 and ReGH115, show a different mode-of-action towards glucuronoxylan and glucuronoxylo oligosaccharides. AB - BACKGROUND: The production of biofuels and biochemicals from grass-type plant biomass requires a complete utilisation of the plant cellulose and hemicellulosic xylan via enzymatic degradation to their constituent monosaccharides. Generally, physical and/or thermochemical pretreatments are performed to enable access for the subsequent added carbohydrate-degrading enzymes. Nevertheless, partly substituted xylan structures remain after pretreatment, in particular the ones substituted with (4-O-methyl-)glucuronic acids (UAme). Hence, alpha glucuronidases play an important role in the degradation of UAmexylan structures facilitating the complete utilisation of plant biomass. The characterisation of alpha-glucuronidases is a necessity to find the right enzymes to improve degradation of recalcitrant UAmexylan structures. RESULTS: The mode-of-action of two alpha-glucuronidases was demonstrated, both obtained from the fungus Rasamsonia emersonii; one belonging to the glycoside hydrolase (GH) family 67 (ReGH67) and the other to GH115 (ReGH115). Both enzymes functioned optimal at around pH 4 and 70 degrees C. ReGH67 was able to release UAme from UAme substituted xylo-oligosaccharides (UAmeXOS), but only the UAme linked to the non reducing end xylosyl residue was cleaved. In particular, in a mixture of oligosaccharides, UAmeXOS having a degree of polymerisation (DP) of two were hydrolysed to a further extent than longer UAmeXOS (DP 3-4). On the contrary, ReGH115 was able to release UAme from both polymeric UAmexylan and UAmeXOS. ReGH115 cleaved UAme from both internal and non-reducing end xylosyl residues, with the exception of UAme attached to the non-reducing end of a xylotriose oligosaccharide. CONCLUSION: In this research, and for the first time, we define the mode-of-action of two alpha-glucuronidases from two different GH families both from the ascomycete R. emersonii. To date, only four alpha-glucuronidases classified in GH115 are characterised. ReGH67 showed limited substrate specificity towards only UAmeXOS, cleaving UAme only when attached to the non reducing end xylosyl residue. ReGH115 was much less substrate specific compared to ReGH67, because UAme was released from both polymeric UAmexylan and UAmeXOS, from both internal and non-reducing end xylosyl residues. The characterisation of the mode-of-action of these two alpha-glucuronidases helps understand how R. emersonii attacks UAmexylan in plant biomass and the knowledge presented is valuable to improve enzyme cocktails for biorefinery applications. PMID- 27195023 TI - AutoDock VinaXB: implementation of XBSF, new empirical halogen bond scoring function, into AutoDock Vina. AB - BACKGROUND: Halogen bonding has recently come to play as a target for lead optimization in rational drug design. However, most docking program don't account for halogen bonding in their scoring functions and are not able to utilize this new approach. In this study a new and improved halogen bonding scoring function (XBSF) is presented along with its implementation in the AutoDock Vina molecular docking software. This new improved program is termed as AutoDock VinaXB, where XB stands for the halogen bonding parameters that were added. RESULTS: XBSF scoring function is derived based on the X...A distance and C-X...A angle of interacting atoms. The distance term was further corrected to account for the polar flattening effect of halogens. A total of 106 protein-halogenated ligand complexes were tested and compared in terms of binding affinity and docking poses using Vina and VinaXB. VinaXB performed superior to Vina in the majority of instances. VinaXB was closer to native pose both above and below 2 A deviation categories almost twice as frequently as Vina. CONCLUSIONS: Implementation of XBSF into AutoDock Vina has been shown to improve the accuracy of the docking result with regards to halogenated ligands. AutoDock VinaXB addresses the issues of halogen bonds that were previously being scored unfavorably due to repulsion factors, thus effectively lowering the output RMSD values. PMID- 27195022 TI - Examination of the effects of Campylobacter concisus zonula occludens toxin on intestinal epithelial cells and macrophages. AB - BACKGROUND: Campylobacter concisus is a Gram-negative bacterium that is associated with inflammatory bowel disease (IBD). Some C. concisus strains carry zonula occludens toxin (zot) gene which has polymorphisms. This study investigated the effects of C. concisus Zot on intestinal epithelial cells and macrophages using cell line models. METHODS: Campylobacter concisus zot (808T) gene, a polymorphism that is associated with active IBD, was cloned and expressed in Escherichia coli. The effects of C. concisus Zot on intestinal epithelial barrier were examined using Caco-2 cell model. Apoptosis induced by C. concisus Zot in Caco-2 cells was assessed by measuring the levels of caspase 3/7. The production of pro-inflammatory cytokines induced by C. concisus Zot in HT-29 cells and in THP-1 macrophage-like cells was measured using ELISA kits. Whether exposure to C. concisus Zot can affect the responses of macrophages to E. coli K12 was also investigated. RESULTS: Campylobacter concisus Zot caused prolonged intestinal epithelial barrier damage, induced intestinal epithelial cell apoptosis, induced epithelial production of TNF-alpha and IL-8 and upregulated TNF-alpha in THP-1 macrophage-like cells. Pre-exposure to C. concisus Zot significantly enhanced the production of TNF-alpha and IL-8 as well as phagocytosis by THP-1 macrophage-like cells in response to E. coli K12. CONCLUSION: This study suggests that C. concisus Zot may have enteric pathogenic potential by damaging intestinal epithelial barrier, inducing intestinal epithelial and macrophage production of proinflammatory cytokines in particular TNF-alpha and enhancing the responses of macrophages to other enteric bacterial species. PMID- 27195021 TI - Setdb1-mediated H3K9 methylation is enriched on the inactive X and plays a role in its epigenetic silencing. AB - BACKGROUND: The presence of histone 3 lysine 9 (H3K9) methylation on the mouse inactive X chromosome has been controversial over the last 15 years, and the functional role of H3K9 methylation in X chromosome inactivation in any species has remained largely unexplored. RESULTS: Here we report the first genomic analysis of H3K9 di- and tri-methylation on the inactive X: we find they are enriched at the intergenic, gene poor regions of the inactive X, interspersed between H3K27 tri-methylation domains found in the gene dense regions. Although H3K9 methylation is predominantly non-genic, we find that depletion of H3K9 methylation via depletion of H3K9 methyltransferase Set domain bifurcated 1 (Setdb1) during the establishment of X inactivation, results in failure of silencing for around 150 genes on the inactive X. By contrast, we find a very minor role for Setdb1-mediated H3K9 methylation once X inactivation is fully established. In addition to failed gene silencing, we observed a specific failure to silence X-linked long-terminal repeat class repetitive elements. CONCLUSIONS: Here we have shown that H3K9 methylation clearly marks the murine inactive X chromosome. The role of this mark is most apparent during the establishment phase of gene silencing, with a more muted effect on maintenance of the silent state. Based on our data, we hypothesise that Setdb1-mediated H3K9 methylation plays a role in epigenetic silencing of the inactive X via silencing of the repeats, which itself facilitates gene silencing through alterations to the conformation of the whole inactive X chromosome. PMID- 27195024 TI - The second decade. PMID- 27195025 TI - A structured approach to the assessment of a floppy neonate. AB - Hypotonia in a newborn presents a diagnostic challenge for clinicians. It is an important clinical feature that may indicate an underlying systemic illness or neurological problem at the level of the central or peripheral nervous system. It is important to know the different presentations of hypotonia and to have the knowledge of the diagnostic work up which requires multidisciplinary assessment and input and the prognostic implications of these disorders. This review article presents a structured approach highlighting initial assessment, examination, and management of a neonate with generalized hypotonia. PMID- 27195026 TI - Neonatal cranial sonography: A concise review for clinicians. AB - Cranial sonography continues to hold an important place in neonatal care. Attributes favorable to sonography that make it almost indispensable for routine care of the newborn includes easy access, low cost, portability, lack of ionizing radiations and exemption from sedation or anaesthesia. Cranial sonography has highest impact in neonates suspected to have meningitis and its complications; perinatal ischemia particularly periventricular leukomalacia (PVL); hydrocephalus resulting from multitude of causes and hemorrhage. Not withstanding this, cranial sonography has yielded results for a repertoire of indications. Approach to cranial sonography involves knowledge of the normal developmental anatomy of brain parenchyma for correct interpretation. Correct technique, taking advantage of multiple sonographic windows and variable frequencies of the ultrasound probes allows a detailed and comprehensive examination of brain parenchyma. In this review, we discuss the technique, normal and variant anatomy as well as disease entities of neonatal cranial sonography. PMID- 27195027 TI - Proatlas segmentation anomalies: Surgical management of five cases and review of the literature. AB - OBJECTIVE: Proatlas segementation anomalies are due to defective re-segmentation of the proatlas sclerotome. These anomalies of the craniovertebral junction are rare and have multiple presentations. The aim of this study is to report this author's personal experience in managing five of these patients with different radiological findings necessitating different surgical strategies and to provide a brief review of the relevant literature. MATERIALS AND METHODS: Five patients, all in the second decade of life were treated between 2010 and 2013. There were three males and two females. All the patients presented with spastic quadriparesis and/or cerebellar signs. Patients underwent plain radiographs, MRI and CT of the craniovertebral junction. CT of the cranioveretebral junction was the key to the diagnosis of this anomaly. Postoperatively, patients were assessed with plain radiographs and CT in all patients and MRI in one. RESULTS: Two patients underwent craniovertebral realignment with occipitocervical fixation, two patients underwent C1-C2 fixation using Goel-Harms technique and one patient underwent craniovertebral realignment with C1-C2 fixation using spacers in the atlanatoaxial joint and foramen magnum decompression. All patients improved during follow up. CONCLUSIONS: Proatlas segmentation defects are rare anomalies of the craniovertebral junction. Routine use of thin section CT of the craniovertebral junction and an awareness of this entity and its multivarious presentations are necessary for clinicians dealing with abnormalities of the craniovertebral junction. PMID- 27195028 TI - Adolescent prolapsed lumbar intervertebral disc: Management strategies and outcome. AB - OBJECTIVE: Lumbar intervertebral disc herniation (LIVDH) is rare in children and adolescents when compared to adults. In literature, children generally constitute around 0.5-3% of surgically treated LIVDH. Though much rarer, they are less likely to respond to conservative treatment than adults. In this study, we analyze our experience in the management of adolescent LIVDH (ALIVDH) (age group 12-18 years) including the demographic, clinico-radiological features; surgical management strategies and outcome. MATERIALS AND METHODS: This retrospective analysis constituted all patients between 12 and 18 years, who underwent surgery for LIVDH at our institute over a period of 15 years from January 1999 to June 2014. The records of these patients were retrieved, and demographic features, clinical picture, radiological features, operative findings, and postoperative events were evaluated. Follow-up data were obtained either through direct clinical evaluation or mailed self-report questionnaire and telephone conversations. The long-term outcome was analyzed by using standardized and condition specific outcome scales in addition to routine clinical follow-up evaluation. The long-term outcome was analyzed by using the short form-36 (SF 36). RESULTS: There were a total of 32 patients (26 males, eight females) with an average age of 15.64 years. Trauma was a significant etiological factor 57.14% (n = 16/28). Vertebral anomalies were present in 35.7% (n = 10/28) cases. Majority had a neurological deficit at presentation (n = 20/28). The most commonly involved level was the L4-L5 level (n = 18/128) in this series. Multiple level disc degeneration was present in eight patients (28.6%). Immediate postoperative relief was achieved in all but one patient. At long-term follow-up twenty patients were pain-free (71.4%). At follow-up, the physical functioning scale of SF-36 was significantly lower in patients with gross motor deficit prior to surgery. CONCLUSIONS: Early diagnosis and adequate management contribute to a good outcome. In our study, trauma and presence of preexisting vertebral anomalies were significant factors in the etiogenesis of ALIVDH. PMID- 27195029 TI - Effect of therapeutic hypothermia on chromosomal aberration in perinatal asphyxia. AB - INTRODUCTION: Perinatal asphyxia is a major cause for neonatal mortality and morbidity around the world. The reduction of O2 results in the generation of reactive oxygen species which interact with nucleic acid and make alteration in the structure and functioning of the genome. We studied the effect of therapeutic hypothermia on chromosomes with karyotyping. SUBJECTS AND METHODS: Babies in the hypothermia group were cooled for the first 72 h, using gel packs. Rectal temperature of 33-34 degrees C was maintained. Blood sample was collected after completion of therapeutic hypothermia for Chromosomal analysis. It was done with IKAROS Karyotyping system, Metasystems, based on recommendations of International system of human cytogenetic nomenclature. RESULTS: The median chromosomal aberration was lower in hypothermia [2(0-5)] than control group [4(1-7)] and chromatid breakage was commonest aberration seen. Chromosomal aberration was significantly higher in severe encephalopathy group than moderate encephalopathy group. CONCLUSION: We conclude that the TH significantly reduces DNA damage in perinatal asphyxia. PMID- 27195030 TI - Pediatric interhemispheric arachnoid cyst: An institutional experience. AB - BACKGROUND: Interhemispheric arachnoid cysts (IHACs) are a rare type of congenital arachnoid cyst accounting for <5% of all cases. The optimum surgical management of symptomatic IHAC is still controversial, and there are no clear guidelines. MATERIALS AND METHODS: Retrospective analysis of six pediatric patients of IHAC operated from 2012 to 2015 at our institute. There was definitive sex predisposition with all patients being males. Endoscopic cystoventriculostomy, cystocisternostomy, and cystoperitoneal shunt surgeries were performed in three patients each. RESULTS: The median age at presentation was 13 months. The most common clinical presentations were macrocrania with rapidly increasing head size, seizures, infantile spasms, and developmental delay. The mean duration of follow-up was 24.16 months (range: 3-36 months). Cyst size decreased in all the patients on follow-up imaging. Head size stabilized in all the patients. None of the patients required a second surgical procedure till the last follow-up. CONCLUSIONS: Both endoscopic cyst fenestration and shunt surgery are safe and effective in management of IHAC. PMID- 27195031 TI - Outcome of ventriculoperitoneal shunt surgery, without prior placement of external ventricular drain in Grades III and IV patients of tubercular meningitis with hydrocephalus: A single institution's experience in the pediatric population and review of literature. AB - OBJECTIVE: Hydrocephalus is a most common complication of tubercular meningitis (TBM). Relieving hydrocephalus by ventriculoperitoneal shunt (VPS) placement has been considered beneficial in patient in Palur Grades II or III. The role of VPS placement in those of Grades III and IV is controversial, and general tendency is to avoid its use. Some authors have suggested that patient in Grades III and IV should receive a shunt only if their condition improves with a trial placement of external ventricular drain (EVD). However, recent studies suggest that VPS may be undertaken without the trial of an EVD. Our study prospectively evaluates the role of direct VPS placement in patient in Grades III and IV TBM with hydrocephalus (TBMH). MATERIALS AND METHODS: This study was carried out on 50 consecutive pediatric patients of TBMH in Palur Grades III and IV from July 2013 to December 2014 in R.N.T. Medical College and M.B. Hospital, Udaipur, Rajasthan. All patients underwent direct VPS placement, without prior placement of EVD. The outcome was assessed at the end of 3 months using Glasgow Outcome Score. RESULTS: The mean age of patients was 3.25 years (range, 3 months-14 years). Forty (80%) patients were in Grade III, and 10 (20%) were in Grade IV. Good outcome and mortality in Grade IV patients were 30% (3/10) and 10% (1/10), respectively; whereas in Grade III patients, it was 77.5% (31/40) and 0% (0/40), respectively. Twenty-five patients presented with focal neurological deficit at admission, which persisted in only 14 patients at 3 months follow-up. VPS-related complications were observed in 5 (10%) patients. CONCLUSIONS: This study demonstrates that direct VPS surgery could improve the outcome of Grades III and IV TBMH. Despite poor grade at admission, 80% patients in Grade III and 20% patients in Grade IV had a good outcome at 3 months follow-up. Direct VPS placement is a safe and effective option even in a patient in Grades III and IV grade TBMH with a low complication rate. PMID- 27195032 TI - Transnasal endoscopic repair of pediatric meningoencephalocele. AB - INTRODUCTION: Encephaloceles in relation to the nose are rare lesions affecting the skull base. In the pediatric population, majority are congenital lesions manifesting as nasal masses requiring surgical intervention. MATERIALS AND METHODS: A retrospective study of 6 consecutive patients below 12 years of age with intranasal meningoencephalocele treated by endonasal endoscopic approach at our tertiary centre was done. The follow up period ranged from 6 months to 2 years. A detailed clinical and radiological evaluation of these cases was done. Endonasal endoscopic repair (gasket seal/fat plug) was carried out in all cases. RESULTS: Out of 6 patients, 4 patients had post-traumatic and rest 2 cases had congenital meningo-encephaloceles. All patients were asymptomatic in post operative follow up period. One patient had minor complication of nasal alar collapse due to intra-operative adherence of encephalocele to cartilaginous framework. CONCLUSION: Transnasal endoscopic repair of anterior skull base meningoencephalocele is a minimally invasive single stage surgery, and has advantage in terms of lesser hospital stay, cost of treatment, and better cosmesis. The repair technique should be tailored to the size of defect to provide a water-tight seal for better outcome. PMID- 27195033 TI - A prospective study of magnetic resonance imaging patterns of central nervous system infections in pediatric age group and young adults and their clinico biochemical correlation. AB - BACKGROUND: Infections of the central nervous system (CNS) are common and routinely encountered. Our aim was to evaluate the neuroimaging features of the various infections of the CNS so as to differentiate them from tumoral, vascular, and other entities that warrant a different line of therapy. AIMS: Our aim was to analyze the biochemical and magnetic resonance imaging (MRI) features in CNS infections. SETTINGS AND DESIGN: This was a longitudinal, prospective study over a period of 11/2 years. SUBJECTS AND METHODS: We studied cerebrospinal fluid (CSF) findings and MRI patterns in 27 patients of 0-20 years age group with clinical features of CNS infections. MRI was performed on MAGNETOM Avanto 18 Channel 1.5 Tesla MR machine by Siemens India Ltd. The MRI protocol consisted of diffusion-weighted and apparent diffusion coefficient imaging, turbo spin echo T2 weighted, spin echo T1-weighted, fluid-attenuated inversion recovery (FLAIR), and gradient-echo in axial, FLAIR in coronal, and T2-weighted in sagittal plane. Contrast-enhanced T1-weighted sequence and MR spectroscopy were done whenever indicated. RESULTS AND CONCLUSIONS: We found that most of the children belong to 1-10 years age group. Fungal infections were uncommon, mean CSF adenosine deaminase values specific for tuberculosis and mean CSF glucose-lowered in pyogenic. Hemorrhagic involvement of thalamus with/without basal ganglia and brainstem involvement may indicate Japanese encephalitis or dengue encephalitis. Diffusion restriction or hemorrhage in not expected in the brainstem afflicted lesions of rabies. Congenital cytomegalovirus can cause cortical malformations. T1 hyperintensities with diffusion restriction may represent viral encephalitis. Lesions of acute disseminated encephalomyelitis (ADEM) may mimic viral encephalitis. Leptomeningeal enhancement is predominant in pyogenic meningitis. Basilar meningitis in the presence of tuberculomas is highly sensitive and specific for tuberculosis. PMID- 27195034 TI - Spontaneous extradural hemorrhage due to Langerhans cell histiocytosis of the skull in a child: A rare presentation. AB - Eosinophilic granuloma (EG) represents a local form of Langerhans cell histiocytosis that occurs mostly in children. It usually presents with a gradually enlarging painless skull mass, and rarely presents a rapid clinical deterioration. This 7-year-old boy who was diagnosed with EG, based on a magnetic resonance imaging scan, after presenting with a painless right parietal swelling of 7-week duration. Three weeks prior his scheduled surgery, he presented to the emergency department with a 2-day history of sudden increased of the subcutaneous swelling associated with a headache, vomiting, and decreased the level of consciousness; there was no history of trauma. Brain computed tomography revealed a right parietal bone defect with large subgaleal and extradural hematoma. He underwent emergent surgical excision of the skull lesion and evacuation of the hematoma. Histopathological examination confirmed the diagnosis of EG. We aim to raise the awareness of physicians of this rare spontaneous hemorrhagic complication of EG and review the literature. PMID- 27195035 TI - Juvenile amyotrophic lateral sclerosis: Classical wine glass sign on magnetic resonance imaging. AB - Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig disease, is a chronic degenerative neurologic disease and is characterized by the selective involvement of the motor system. Usually, patients present with upper motor neuron (UMN) and lower motor neuron compromise. Degeneration of the UMN in the cerebral cortex is one of the main pathologic changes in ALS. These changes usually affect corticospinal tracts leading to degeneration of the fibers which show characteristic hyperintensities along the tracts leading to the "wine glass sign." Patients with ALS usually present in the sixth decade of life; presentation in pediatric age in the form of juvenile ALS being rare. PMID- 27195036 TI - Rare clinical presentation of diffuse large B-cell lymphoma as otitis media and facial palsy. AB - Extra nodal presentation of Non Hodgkins Lymphoma (NHL) is a rare entity, and data available about the NHL that primarily involves of middle ear and mastoid is limited. We report a case of diffuse large B cell lymphoma (DLBCL), in a 2 year 8 month old boy, who developed otalgia and facial palsy. Computed tomography revealed a mass in the left mastoid. Mastoid exploration and histopathological examination revealed DLBCL. This case highlights the importance of considering malignant lymphoma as one of the differential diagnosis in persistent otitis media and/facial palsy. PMID- 27195037 TI - Uncommon presentation of choroid plexus papilloma in an infant. AB - Choroid plexus tumors are relatively rare primary brain tumors that arise from the epithelial differentiated tissue, majority being well-differentiated papillomas. In adults, fourth ventricle and in children, lateral ventricles are the most common site of these tumors. We reported a case of choroid plexus papilloma in the temporal horn of lateral ventricle in a female child who presented with the uncommon symptoms of sudden intraventricular hemorrhage and multiple episodes of seizure without symptoms of raised intracranial tension. PMID- 27195038 TI - Atypical rhabdoid tumor of lateral ventricle: Report of an unusual tumor. AB - Supratentorial atypical teratoid rhabdoid tumors (AT/RTs) of infancy and childhood are rare, highly malignant neoplasms, most common in the first 2 years of life. In spite of multiple treatment regimens consisting of surgical resection, radiation therapy, and multi-agent chemotherapy, the prognosis is very poor. The majority of these tumors are located in the cerebellum, cerebellopontine angle, pineal gland, spinal cord, and the suprasellar region; supratentorial location is relatively uncommon, and the intraventricular location is extremely rare. We report a rare case of AT/RT arising in the lateral ventricle in a 4-year-old patient. PMID- 27195039 TI - Sjogren-Larsson syndrome: A rare neurocutaneous disorder. AB - Sjogren-Larsson syndrome is an autosomal recessive disorder characterized by defective activity of fatty aldehyde dehydrogenase. It presents as a triad of congenital ichthyosis, spastic diplegia, and mental retardation. The pathology behind this syndrome is the failure of degradation of fatty aldehydes. This case is presented for its rarity. PMID- 27195040 TI - Guillain-Barre syndrome with hyperreflexia and bilateral papillitis in a child. AB - Guillain-Barre syndrome (GBS) is an acute inflammatory polyneuropathy characterized by rapidly progressive symmetric weakness, and areflexia. Areflexia is necessary for the diagnosis of GBS. However, recently there have been studies of hyperreflexia with axonal neuropathy form of GBS. We report a 14-year-old boy with GBS, who presented with hyperreflexia and bilateral papillitis. To the best of our knowledge, this is the first pediatric patient presenting with papillitis and hyperreflexia with acute motor and sensory axonal neuropathy form of GBS. PMID- 27195041 TI - The maladies of malabsorption. AB - Malabsorption syndrome (MAS) is a common condition in India. In Indian adults, tropical sprue and celiac disease are leading causes of MAS. Sometimes, the diagnosis of MAS may pose a challenge due to the varied signs and symptoms. We present a case of MAS in a young female, whose presenting symptoms were mainly neurological. She was successfully treated under regular follow-up for the past 6 years without any symptoms. PMID- 27195042 TI - Distal cord-predominant longitudinally extensive myelitis with diffuse spinal meningitis and dural abscesses due to occult tuberculosis: A rare occurrence. AB - Tuberculous myelitis usually involves thoracic and only rarely, distal cord. Longitudinal lesions more than three spinal segments long in tuberculosis (TB) are usually due to intramedullary tuberculomas and not infectious myelitis. We report a 17-year-old male with acute myelitis from D7 to conus medullaris, diffuse spinal meningitis, subdural and epidural abscesses, normal vertebrae, intervertebral discs, and brain imaging. Cerebrospinal fluid (CSF) showed raised proteins, lymphocytosis, hypoglycorrhagia, and positive TB-polymerase chain reaction. Chest X-ray was normal, and sputum was negative for acid-fast Bacilli. Chest computed tomography (CT) revealed endobronchial TB. The patient was successfully treated with antitubercular drugs and steroids. In endemic areas, a high index of suspicion should be kept for TB in patients with myelitis, especially those with spinal abscesses and a suggestive CSF report. In selected cases, there may be a role of CT scan inspite of normal X-ray. PMID- 27195043 TI - Attention deficit hyperactivity disorder presenting as dermatitis artefacta. AB - Dermatitis artefacta, a self-inflicted intentional dermatosis is a very rare diagnosis in childhood. In a large proportion, the underlying psychiatric disorders go unidentified due to lack of collaboration between dermatologist and psychiatrist. The underlying psychological reasons for childhood dermatitis artefacta include emotional distress and interpersonal conflicts. A multitude of psychosocial factors interact to precipitate this disorder. Here, we report a child with dermatitis artefacta who was diagnosed with attention deficit hyperactivity disorder during psychiatric evaluation. Parental expectations and sibling rivalry were further increasing the stress of the index child. Appropriate diagnosis and management lead to treatment compliance and functional improvement in the child. PMID- 27195044 TI - Warburg micro syndrome in siblings from India. AB - Warburg syndrome is a rare disorder characterized by microcephaly, microcornea, congenital cataract, developmental delay, and hypogonadism. Here, we report two siblings from India who presented with developmental delay, microcornea, microphthalmia, and bilateral congenital cataracts, born to the third-degree consanguineously married couple. Both children had hypoplasia of corpus callosum. In this report, we aim to highlight and compare clinical features of these two cases with previously reported cases. PMID- 27195045 TI - Tuberculous meningitis sequelae as basal cisternal calcifications. PMID- 27195046 TI - Magnetic resonance imaging and magnetic resonance spectroscopy in Salmonella meningoencephalitis. PMID- 27195047 TI - Primary amebic meningoencephalitis: Summarization on cases with early diagnosis by identification of amebae trophozoite in the cerebrospinal fluid. PMID- 27195048 TI - Ventriculitis and hydrocephalus with hypoglycorrhachia in congenital toxoplasma infection. PMID- 27195049 TI - Ethmocephaly: A rare cephalic disorder. PMID- 27195050 TI - LGBT in the Military: Policy Development in Sweden 1944-2014. AB - This article contributes to the growing field of research on military LGBT policy development by exploring the case of Sweden, a non-NATO-member nation regarded as one of the most progressive in terms of the inclusion of LGBT personnel. Drawing on extensive archival work, the article shows that the story of LGBT policy development in the Swedish Armed Forces from 1944 to 2014 is one of long periods of status quo and relative silence, interrupted by leaps of rapid change, occasionally followed by the re-appearance of discriminatory policy. The analysis brings out two periods of significant change, 1971-1979 and 2000-2009, here described as turns in LGBT policy. During the first turn, the military medical regulation protocol's recommendation to exempt gay men from military service was the key issue. During these years, homosexuality was classified as mental illness, but in the military context it was largely framed in terms of security threats, both on a national level (due to the risk of blackmail) and for the individual homosexual (due to the homophobic military environment). In the second turn, the focus was increasingly shifted from the LGBT individual to the structures, targeting the military organization itself. Furthermore, the analysis shows that there was no ban against LGBT people serving in the Swedish Armed Forces, but that ways of understanding and regulating sexual orientation and gender identity have nonetheless shaped the military organization in fundamental ways, and continue to do so. PMID- 27195051 TI - They called it the 'abominable crime': an analysis of heterosexual support for anti-gay laws in Barbados, Guyana and Trinidad and Tobago. AB - The aim of this study was to evaluate support for current buggery/sodomy laws in three Caribbean countries-Barbados, Guyana and Trinidad and Tobago. To complete this task, data from the 2013 Caribbean Development Research Services (CADRES) 'Attitudes towards homosexuals' surveys were employed. The data analysis revealed that a majority of heterosexuals in the sample generally supported the maintenance and enforcement of the anti-gay laws, and the main predictors of said support were race, country of residence, religiosity, interpersonal contact and beliefs about the origins of homosexuality. PMID- 27195052 TI - Stage I and II Stress Incontinence (SIC): High dosed vitamin D may improve effects of local estriol. AB - After the age of 55 almost every third woman suffers from conditions of the incapability to retain urine when the intra-abdominal pressure is raised by different causes. So called stress incontinence. It' s caused by a predisposition in the family, weakness of the tissue, physical strain, deficiency in the metabolism, especially an increasing local estrogen deficiency and a local and systemic vitamin D deficiency. PATIENTS: We evaluated the data of 60 meno- and postmenopausal female patients with a stress incontinence (SIC). All had a SIC in spite of a former local estriol treatment with a treatment of OeKolp(r) forte (= 0.5 mg estriol/ov), 3 times a week, for 6 weeks and in spite of a regular pelvic floor exercise for 6 weeks in the morning and in the evening, according to the protocol. Thirty were in stage I SIC and 30 were in stage II SIC. METHOD: We evaluated vitamin-D-levels in serum of our 60 postmenopausal women. Only 20% of this group had good vitamin D-levels. The medical intervention combined estriol (0.5 mg) together with high dosed vitamin D (12.500 I.U.) locally 3 times a week for a period of 6 weeks. The patients also had the instruction to continue their daily exercises in pelvic floor (morning and evening, due to their protocol). After six weeks of treatment the vitamin D level in serum was defined and correlated to the patients condition (symptomatic of stress incontinence, protocol of micturitions, Pad-test). RESULTS: About one-third of women from our test assigned to be now capable of retaining urine. More than one-third of our patients cleared a profit of treatment. They reported mimimum regression about 25% of volume of incontinence. Therefore more than 2-third of our women being incapable of retaining urine improved their body conditions by using a combination of locally administered etriol and high dosed vitamin D. CONCLUSION: Stress incontinence (being incapable of retaining urine when the intra-abdominal pressure arises) in lower and middle grade, improves their body conditions under a combination of local administered estriol and vitamin D. This small study is not representative. We need much bigger studies with much more dates and with a follow up. PMID- 27195053 TI - Local corticosterone activation by 11beta-hydroxysteroid dehydrogenase 1 in keratinocytes: the role in narrow-band UVB-induced dermatitis. AB - Keratinocytes are known to synthesize cortisol through activation of the enzyme 11beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1). To confirm the function of 11beta-HSD1 in keratinocytes during inflammation in vivo, we created keratinocyte specific-11beta-HSD1 knockout mice (K5-Hsd11b1-KO mice) and analyzed the response to narrow-band ultraviolet B (NB-UVB) irradiation. Firstly, we measured the mRNA and protein levels of 11beta-HSD1 following NB-UVB irradiation and found that the expression of 11beta-HSD1 in keratinocytes of mouse ear skin was enhanced at 3 and 24 hours after 250 mJ/cm(2), 500 mJ/cm(2), 1 J/cm(2), and 2 J/cm(2) NB-UVB irradiation. Next, we determined that 24 hours after exposure to 1 J/cm(2) NB-UVB irradiation, the numbers of F4/80-, CD45-, and Gr-1-positive cells were increased in K5-Hsd11b1-KO mice compared to wild type (WT) mice. Furthermore, the expression of the chemokine (C-X-C-motif) ligand 1 (CXCL1) and interleukin (IL)-6 was also significantly enhanced in NB-UVB-irradiated K5-Hsd11b1-KO mice compared with WT mice. In addition, activation of nuclear factor-kappa B (NF-kappaB) after NB-UVB irradiation was enhanced in K5-Hsd11b1-KO mice compared to that in WT mice. Thus, NB-UVB-induced inflammation is augmented in K5-Hsd11b1-KO mice compared with WT mice. These results indicate that 11beta-HSD1 may suppress NB UVB-induced inflammation via inhibition of NF-kappaB activation. PMID- 27195054 TI - TNF-alpha increases the expression and activity of vitamin D receptor in keratinocytes: role of c-Jun N-terminal kinase. AB - Several inflammatory mediators increase calcitriol production by epidermal keratinocytes. In turn calcitriol attenuates the keratinocyte inflammatory response. Since the effect of the in-situ generated calcitriol depends also on the sensitivity to the hormone we studied the effect of inflammatory cytokines on the response of HaCaT human keratinocytes to calcitriol by examining the expression and transcriptional activity of VDR. Treatment with TNF, but not with IL-1beta or interferon gamma, increased VDR protein level, while decreasing the level of its heterodimerization partner RXRalpha. This was associated with increased VDR mRNA levels. c-Jun N-terminal kinase, but not P38 MAPK or NFkappaB, was found to participate in the upregulation of VDR by TNF. The functional significance of the modulation of VDR and RXRalpha levels by TNF is manifested by increased induction of VDR target gene CYP24A1 by calcitriol. Calcitriol, in turn, inhibited the enhanced expression of VDR by TNF. In conclusion, the inflammatory cytokine TNF increases the response of keratinocytes to calcitriol through upregulation of its receptor VDR, which in turn is subject to negative feedback by the hormone accelerating the return of the keratinocyte vitamin D system to its basal activity. We surmise that the increased generation and sensitivity to calcitriol in keratinocytes play a role in the resolution of epidermal inflammation. PMID- 27195058 TI - A note on the falsification of the ionic theory of hair cell transduction. PMID- 27195057 TI - Insights, attitudes, and perceptions about asthma and its treatment: a multinational survey of patients from Europe and Canada. AB - BACKGROUND: Asthma surveys completed within the past 10 years in the Americas and the Asia-Pacific region have shown significant underassessment of asthma severity in addition to undertreatment of asthma and have suggested the need to improve long-term asthma management. In this study, we examined the frequency of asthma symptoms and severe episodes, patients' perceived asthma control, and use of asthma medications in Europe and Canada. METHODS: The Asthma Insight and Management survey (54 questions) was conducted in Europe (Germany, Italy, Spain and the United Kingdom) and Canada from June 14 through July 28, 2010. Telephone interviews were conducted with randomly screened patients or parents of adolescents (aged 12-17 years) with asthma; patients younger than 12 years of age were excluded from the survey. Responses were reported separately for each country and in total for all five countries. RESULTS: Seventy-five thousand three hundered thirty-five households were screened, and 2003 patients were interviewed. The survey respondents represented a wide range of severity. Overall, 26 % of patients reported symptoms daily or most days over the past 4 weeks, but most patients (81 %) perceived their asthma to be well or completely controlled. Over the past year, 41 % of patients had episodes of frequent/severe symptoms, and 50 % reported acute treatment (e.g. hospitalization, emergency visit, unscheduled physician visit) for asthma. Across countries, 52 % of patients reported taking controller medication every day over the past year, 27 % reported not taking any controller medication, and 14 % reported stopping controller treatment for 3 months or longer the last time they stopped. Many patients considered asthma well controlled if each year they had only two urgent doctor visits (50 %), three or four exacerbations (60 %), and/or one emergency room visit (41 %). DISCUSSION: This is the largest survey of patients with asthma in Europe and Canada in more than a decade. CONCLUSION: In 2010, many surveyed patients in Europe and Canada reported features indicating uncontrolled asthma, yet the majority believed they were well controlled, indicating that they had low expectations of long-term asthma management. Use of controller medications was substantially less than recommended in treatment guidelines. PMID- 27195056 TI - Solar radiation and the incidence and mortality of leading invasive cancers in the United States. AB - Invasive cancer risk is inversely related to ultraviolet light exposure. This study explores relationships between cancer and the satellite-derived sunlight energy. We obtained the North America Land Data Assimilation System (NLDAS) daily average sunlight for the continental United States from 1999-2011. US Cancer Statistics age-adjusted-incidence and mortality was also obtained from the Centers for Disease Control and Prevention (CDC). We found that cancer incidence for all invasive cancers and for 11 of 22 leading cancers significantly decreased with increased solar radiation. Cancer mortality for all invasive cancers was not significantly associated with solar radiation, but for 7 of 22 leading cancers, including cancers of the uterus, leukemias, lung, ovary, and urinary bladder, increased solar radiation predicted decreased mortality. With increasing solar radiation, increased incidence and cancer mortality was observed for liver cancer and increased incidence but not mortality was observed for cervical cancer. The current study confirms studies relating UV radiation to the incidence and mortality of a variety of cancer types. We find associations between solar radiation energy and the incidence and mortality of a number of types of cancers. PMID- 27195059 TI - Desire-state attribution: Benefits of a novel paradigm using the food-sharing behavior of Eurasian jays (Garrulus glandarius). AB - In recent years, we have investigated the possibility that Eurasian jay food sharing might rely on desire-state attribution. The female's desire for a particular type of food can be decreased by sating her on it (specific satiety) and the food sharing paradigm can be used to test whether the male's sharing pattern reflects the female's current desire. Our previous findings show that the male shares the food that the female currently wants. Here, we consider 3 simpler mechanisms that might explain the male's behavior: behavior reading, lack of self other differentiation and behavioral rules. We illustrate how we have already addressed these issues and how our food sharing paradigm can be further adapted to answer outstanding questions. The flexibility with which the food sharing paradigm can be applied to rule out alternative mechanisms makes it a useful tool to study desire-state attribution in jays and other species that share food. PMID- 27195060 TI - Novel mRNA-silencing bodies at the synapse: A never-ending story. AB - Several cellular responses depend on translational regulation and in most cases, this involves the formation of cytoplasmic granules that contain repressed mRNAs. In neurons, numerous mRNAs travel along dendrites to be locally regulated upon synapse activity and we have recently shown that the exoribonuclease XRN1 forms dynamic aggregates at the post synapse that respond to specific stimuli.(1) These foci were termed SX-bodies and are distinct from stress granules (SGs), processing bodies (PBs) and other RNA granules previously described. Together with Smaug1-foci and FMRP-granules, the SX-bodies contribute to dynamically shape the transcriptome available for translation at the post-synapse. PMID- 27195061 TI - Smaug variants in neural and non-neuronal cells. AB - Mammalian Smaug1/Samd4a is an mRNA regulator involved in synapse plasticity and additional non-neuronal functions. Here we analyzed the expression of Smaug1/Samd4a variants and Smaug2/Samd4b in primary hippocampal neurons and non neuronal cell lines. We found that multiple Smaug proteins are present in several mammalian cell lines, including a canonical full length Smaug1, a Smaug1 variant that lacks the third exon, termed DeltaEIII, and Smaug2, the product of a highly homologous gene. These three major isoforms are expressed differentially along neuron development and form cytosolic bodies when transfected in cell lines. By using luciferase reporters, we found that the DeltaEIII isoform, which lacks 10 amino acids in the sterile alpha motif involved in RNA binding, shows a RNA binding capacity and repressor activity comparable to that of the full length Smaug1. These observations are an important groundwork for molecular studies of the Smaug post-transcriptional pathway, which is relevant to neuron development, mitochondrial function and muscle physiology in health and disease. PMID- 27195055 TI - The role of geographical ecological studies in identifying diseases linked to UVB exposure and/or vitamin D. AB - Using a variety of approaches, researchers have studied the health effects of solar ultraviolet (UV) radiation exposure and vitamin D. This review compares the contributions from geographical ecological studies with those of observational studies and clinical trials. Health outcomes discussed were based on the author's knowledge and include anaphylaxis/food allergy, atopic dermatitis and eczema, attention deficit hyperactivity disorder, autism, back pain, cancer, dental caries, diabetes mellitus type 1, hypertension, inflammatory bowel disease, lupus, mononucleosis, multiple sclerosis, Parkinson disease, pneumonia, rheumatoid arthritis, and sepsis. Important interactions have taken place between study types; sometimes ecological studies were the first to report an inverse correlation between solar UVB doses and health outcomes such as for cancer, leading to both observational studies and clinical trials. In other cases, ecological studies added to the knowledge base. Many ecological studies include other important risk-modifying factors, thereby minimizing the chance of reporting the wrong link. Laboratory studies of mechanisms generally support the role of vitamin D in the outcomes discussed. Indications exist that for some outcomes, UVB effects may be independent of vitamin D. This paper discusses the concept of the ecological fallacy, noting that it applies to all epidemiological studies. PMID- 27195062 TI - The flippase DnfB is cargo of fimbrin-associated endocytosis in Aspergillus nidulans, and likely recycles through the late Golgi. PMID- 27195063 TI - NADPH oxidases promote apoptosis by activating ZNRF1 ubiquitin ligase in neurons treated with an exogenously applied oxidant. AB - Reactive oxygen species (ROS) play an important role in causing neuronal death in a number of neurological disorders. We recently reported that ROS serve as a signal to activate neuronal apoptosis and axonal degeneration by activating ZNRF1 (zinc- and RING-finger 1), a ubiquitin ligase that targets AKT for proteasomal degradation in neurons. In the present study, we showed that the NADPH oxidase family of molecules is required for ZNRF1 activation by epidermal growth factor receptor (EGFR)-dependent phosphorylation in response to axonal injury. We herein demonstrate that NADPH oxidases promote apoptosis by activating ZNRF1, even in neurons treated with an exogenously applied oxidant. These results suggest an important role for NADPH oxidase in the initiation/promotion of neuronal degeneration by increasing ROS in close proximity to protein machineries, including those for ZNRF1 and EGFR, thereby promoting neuronal degeneration. PMID- 27195065 TI - The role of phytophagy by predators in shaping plant interactions with their pests. AB - Zoophytophagy is common among predacious arthropods, but research on their role in plant-herbivore interactions is generally focused on predation effects whereas their phytophagy is largely neglected. Our recent study revealed the ability of zoophytophagous predators to induce defense related traits and to affect herbivore performance apart from predation through the plant. Additionally, we show here that predator-exposed plants suffer less damage compared to unexposed plants. Thus, zoophytophagous organisms likely shape community structure by both their predation on herbivores and their phytophagy. Here, we consider zoophytophagous predators as plant vaccination factors and outline how their dual role in affecting herbivores may impact their use in biological pest control. Because plant responses to phytophagy and phytopathogens are known to interact, zoophytophagous predators may also affect plant-pathogen interactions. When we consider these indirect interactions with different plant pest organisms, we will likely better understand the ecology of the complex relationships among plants, herbivores and predators. Moreover, a comprehensive knowledge on the effects of the phytophagy of predators in these ecological interactions will potentially allow us to enhance sustainability in pest control. PMID- 27195064 TI - A novel imaging method revealed phosphatidylinositol 3,5-bisphosphate-rich domains in the endosome/lysosome membrane. AB - We developed a new method to observe distribution of phosphatidylinositol 3,5 bisphosphate [PtdIns(3,5)P2] using electron microscopy. In freeze-fracture replicas of quick-frozen samples, PtdIns(3,5)P2 was labeled specifically using recombinant ATG18 tagged with glutathione S-transferase and 4*FLAG, which was mixed with an excess of recombinant PX domain to suppress binding of ATG18 to phosphatidylinositol 3-phosphate. Using this method, PtdIns(3,5)P2 was found to be enriched in limited domains in the yeast vacuole and mammalian endosomes. In the yeast vacuole exposed to hyperosmolar stress, PtdIns(3,5)P2 was distributed at a significantly higher density in the intramembrane particle (IMP)-deficient liquid-ordered domains than in the surrounding IMP-rich domains. In mammalian cells, PtdIns(3,5)P2 was observed in endosomes of tubulo-vesicular morphology labeled for RAB5 or RAB7. Notably, distribution density of PtdIns(3,5)P2 in the endosome was significantly higher in the vesicular portion than in the tubular portion. The nano-scale distribution of PtdIns(3,5)P2 revealed in the present study is important to understand its functional roles in the vacuole and endosomes. PMID- 27195066 TI - Glycosylphosphatidylinositols: More than just an anchor? AB - There is increasing interest in the role of glycosylphosphatidylinositol (GPI) anchors that attach some proteins to cell membranes. Far from being biologically inert, GPIs influence the targeting, intracellular trafficking and function of the attached protein. Our recent paper demonstrated the role of sialic acid on the GPI of the cellular prion protein (PrP(C)). The "prion diseases" arise following the conversion of PrP(C) to a disease-associated isoform called PrP(Sc) or "prion". Our paper showed that desialylated PrP(C) inhibited PrP(Sc) formation. Aggregated PrP(Sc) creates a signaling platform in the cell membrane incorporating and activating cytoplasmic phospholipase A2 (cPLA2), an enzyme that regulates PrP(C) trafficking and hence PrP(Sc) formation. The presence of desialylated PrP(C) caused the dissociation of cPLA2 from PrP-containing platforms, reduced the activation of cPLA2 and inhibited PrP(Sc) production. We concluded that sialic acid contained within the GPI attached to PrP(C) modifies local membrane microenvironments that are important in PrP-mediated cell signaling and PrP(Sc) formation. PMID- 27195067 TI - So different and still so similar: The plant compound rosmarinic acid mimics bacterial homoserine lactone quorum sensing signals. AB - Apart from inter-bacteria communication quorum sensing (QS) mechanisms also enable inter-domain interactions. To interfere with bacterial QS, plants were found to secrete compounds; most of which of unknown identity. We have identified the plant compound rosmarinic acid (RA) to modulate Pseudomonas aeruginosa QS by binding to the RhlR QS regulator. RA was found to be a homoserine-lactone (HSL) mimic that caused agonistic effects on transcription, resulting ultimately in a stimulation of several RhlR controlled phenotypes like virulence factor synthesis or biofilm formation. Our study was initiated by in silico screening of an RhlR model with compound libraries, demonstrating that this approach is suitable to tackle a major bottleneck in signal transduction research, which is the identification of sensor protein ligands. Previous work has shown that plant compounds interfere with the function of orphan QS regulators. Our study demonstrates that this has not necessarily to be the case since RhlR forms a functional pair with the RhlI synthase. A wide range of structurally dissimilar compounds have been found to mimic HSLs suggesting that this class of QS regulators is characterized by a significant plasticity in the recognition of effector molecules. Further research will show to what extent RA impacts on QS mechanisms of other bacteria. PMID- 27195068 TI - The foundations of cross-modal plasticity. AB - Cross-modal plasticity is a striking adaptive feature of the brain, whereby the loss of one sensory modality induces cortical reorganization that leads to enhanced sensory performance in remaining modalities. Much is known about the macroscopic modifications in the brain that underly cross-modal plasticity and the associated changes in sensory performance. In contrast there is relatively scant information about the molecular and cellular underpinnings of this mechanism. We hypothesized that cross-modal plasticity is a fundamental feature of the nervous system. As such, it should be found in organisms with brains that are substantially less complex than our own. Indeed, we discovered a cross-modal plasticity mechanism in the roundworm Caenorhabditis elegans, whose nervous system is composed of only 302 neurons. Taking advantage of the simplicity of the C. elegans nervous system, we were able to comprehensively study cross-modal plasticity from molecule through circuit to behavior. PMID- 27195069 TI - Vedantic view of life: Reply to Gustavo Caetano-Anolles. AB - The author would like to thank Professor Gustavo Caetano-Anolles from Department of Crop Sciences, University of Illinois for his interest in his work. We may sometimes observe that there is a noticeable difference between the anecdote people narrate about the implications of a scientific paper and the real conclusion of the paper. Prof. Gustavo Caetano-Anolles's response(1) is an ideal example of the same, where he has tried to make great hay about the implications of the article "Life and consciousness - The Vedantic view."(2) The Vedantic view subscribes neither to the views of 'Creationist Movement'/'Intelligent Design', nor it supports some splendid anti-science proposal. Vedantic view refutes the dominant reductionistic view of life in modern biology by proposing a viable alternative concept of 'Organic Whole' and thus serves a scientific critique to the nescience (avidya) that is practiced on the name of science. PMID- 27195070 TI - Fusarium musae infected banana fruits as potential source of human fusariosis: May occur more frequently than we might think and hypotheses about infection. AB - The banana fruit infecting fungus Fusarium musae was originally known as a distinct population within Fusarium verticillioides. However, recently, Fusarium musae was installed as a separate species and the first cases of human infection associated with Fusarium musae were found. In this article, we report an additional survey indicating that human pathogenic Fusarium musae infections may occur more frequently than we might think. Moreover, we evaluate the hypotheses on how infection can be acquired. A first hypothesis is that banana fruits act as carriers of Fusarium musae spores and thereby be the source of human infection with Fusarium musae. Acquisition is likely to be caused through contact with Fusarium musae contaminated banana fruits, either being imported or after traveling of the patient to a banana-producing country. An alternative hypothesis is that Fusarium musae is not only present on banana fruits, but also on other plant hosts or environmental sources. PMID- 27195072 TI - Corrigendum. AB - [This corrects the article DOI: 10.1080/19420889.2015.1123356.]. PMID- 27195071 TI - The biocommunication method: On the road to an integrative biology. AB - Although molecular biology, genetics, and related special disciplines represent a large amount of empirical data, a practical method for the evaluation and overview of current knowledge is far from being realized. The main concepts and narratives in these fields have remained nearly the same for decades and the more recent empirical data concerning the role of noncoding RNAs and persistent viruses and their defectives do not fit into this scenario. A more innovative approach such as applied biocommunication theory could translate empirical data into a coherent perspective on the functions within and between biological organisms and arguably lead to a sustainable integrative biology. PMID- 27195073 TI - Effects of Moderate Aerobic Exercise on Cognitive Abilities and Redox State Biomarkers in Older Adults. AB - We used a moderate aerobic exercise program for 24 weeks to measure the positive impact of physical activity on oxidative stress and inflammatory markers and its association with cognitive performance in healthy older adults. A total of 100 healthy subjects (65-95 Yrs) were randomly classified into two groups: control group (n = 50) and exercise group (n = 50). Cognitive functioning, physical activity score, MDA, 8-OHdG, TAC, and hs-CRP were assessed using LOTCA battery, prevalidated PA questionnaire, and immunoassay techniques. LOTCA 7-set scores of cognitive performance showed a significant correlation with physical activity status and the regulation of both oxidative stress free radicals and inflammatory markers in all older subjects following 24 weeks of moderate exercise. Physically active persons showed a higher cognitive performance along with reduction in the levels of MDA, 8-OHdG, and hs-CRP and increase in TAC activity compared with sedentary participants. Cognitive performance correlated positively with the increase in TAC activity and physical fitness scores and negatively with MDA, 8 OHdG, and hs-CRP, respectively. There was a significant improvement in motor praxis, vasomotor organization, thinking operations, and attention and concentration among older adults. In conclusion, moderate aerobic training for 24 weeks has a positive significant effect in improving cognitive functions via modulating redox and inflammatory status of older adults. PMID- 27195074 TI - The C-ETS2-TFEB Axis Promotes Neuron Survival under Oxidative Stress by Regulating Lysosome Activity. AB - Excessive reactive oxygen species/reactive nitrogen species (ROS/RNS) produced as a result of ageing causes damage to macromolecules and organelles or leads to interference of cell signalling pathways, which in turn results in oxidative stress. Oxidative stress occurs in many neurodegenerative diseases (e.g., Parkinson's disease) and contributes to progressive neuronal loss. In this study, we show that cell apoptosis is induced by oxidative stress and that lysosomes play an important role in cell survival under oxidative stress. As a compensatory response to this stress, lysosomal genes were upregulated via induction of transcription factor EB (TFEB). In addition, localization of TFEB to the nucleus was increased by oxidative stress. We also confirmed that TFEB protects cells from oxidative stress both in vitro and in vivo. Finally, we found that C-ETS2 senses oxidative stress, activates TFEB transcription, and mediates the upregulation of lysosomal genes. Our results demonstrate a mechanistic pathway for inducing lysosomal activity during ageing and neurodegeneration. PMID- 27195077 TI - Keratoconus; a True Corneal Disease. PMID- 27195076 TI - Analytical methods used to quantify isoflavones in cow's milk: a review. AB - This paper provides an update and comprehensive review of the analytical methods used for quantifying isoflavones and their metabolites in cow's milk. Isoflavones are secondary plant metabolites that are similar to 17 beta-estradiol in chemical structure. They form one of the most common categories of phytoestrogens. Numerous health benefits have been attributed to isoflavones, but many of these compounds are also considered to be endocrine disruptors, with adverse effects on health. These contradictory trends offer an attractive prospect for future research, and therefore, sensitive and reliable analytical methods are required to clarify various issues about isoflavones. For this review, a structured methodology was used to select 26 relevant articles published between 2005 and 2015 from the Scopus and CAB Abstract databases. The review discusses individual steps of the analytical procedures described in these articles, including sample preparation, instrumental analysis and validation. The most commonly used analytical procedure is sample preparation involving liquid-liquid extraction and an enzymatic hydrolysis step followed by liquid chromatography with mass spectrometry analysis. Currently, however, there is no standardized procedure for the sample preparation and analysis of isoflavones in milk. PMID- 27195075 TI - Metformin Decreases Reactive Oxygen Species, Enhances Osteogenic Properties of Adipose-Derived Multipotent Mesenchymal Stem Cells In Vitro, and Increases Bone Density In Vivo. AB - Due to its pleiotropic effects, the commonly used drug metformin has gained renewed interest among medical researchers. While metformin is mainly used for the treatment of diabetes, recent studies suggest that it may have further application in anticancer and antiaging therapies. In this study, we investigated the proliferative potential, accumulation of oxidative stress factors, and osteogenic and adipogenic differentiation potential of mouse adipose-derived stem cells (MuASCs) isolated from mice treated with metformin for 8 weeks. Moreover, we investigated the influence of metformin supplementation on mice bone density and bone element composition. The ASCs isolated from mice who were treated with metformin for 8 weeks showed highest proliferative potential, generated a robust net of cytoskeletal projections, had reduced expression of markers associated with cellular senescence, and decreased amount of reactive oxygen species in comparison to control group. Furthermore, we demonstrated that these cells possessed greatest osteogenic differentiation potential, while their adipogenic differentiation ability was reduced. We also demonstrated that metformin supplementation increases bone density in vivo. Our result stands as a valuable source of data regarding the in vivo influence of metformin on ASCs and bone density and supports a role for metformin in regenerative medicine. PMID- 27195078 TI - Screening for MIR184 Mutations in Iranian Patients with Keratoconus. AB - PURPOSE: To investigate whether microRNA (MIR)-184 mutations make a substantial contribution to keratoconus (KCN) among affected Iranian patients. METHODS: A total of 47 Iranian KCN patients, diagnosed based on family history, clinical examinations using slit lamp biomicroscopy, refraction and corneal topography were enrolled in this study. The pri-miR-184 encoding gene obtained from the DNAs of all participants was amplified using polymerase chain reaction and subsequently sequenced by the Sanger dideoxynucleotide protocol. The sequences were compared to MIR184 reference sequence in order to identify sequence variations. The potential effects of a single variation observed on RNA structure was predicted. RESULTS: Only one sequence variation, +39G >T, was observed within the pri-miR-184 encoding sequence in one proband. The patient's KCN-affected sister harbored the same variation. The variation was not novel and was recently shown to be present at similar frequencies among large cohorts of KCN patients and control individuals. CONCLUSION: Mutations in MIR-184 are not a major cause of keratoconus among Iranian patients. The pri-miR-184 sequence needs to be screened in larger cohorts in order to establish whether mutations in the gene are present at low frequencies among Iranian patients. PMID- 27195079 TI - Predictive Ability of Galilei to Distinguish Subclinical Keratoconus and Keratoconus from Normal Corneas. AB - PURPOSE: To determine the predictive ability of different data measured by the Galilei dual Scheimpflug analyzer in differentiating subclinical keratoconus and keratoconus from normal corneas. METHODS: This prospective comparative study included 136 normal eyes, 23 eyes with subclinical keratoconus, and 51 keratoconic eyes. In each eye, keratometric values, pachymetry, elevation parameters and surface indices were evaluated. Receiver operating characteristic (ROC) curves were calculated and quantified by using the area under the curve (AUC) to compare the sensitivity and specificity of the measured parameters and to identify optimal cutoff points for differenciating subclinical keratoconus and keratoconus from normal corneas. Several model structures including keratometric, pachymetric, elevation parameters and surface indices were analyzed to find the best model for distinguishing subclinical and clinical keratoconus. The data sets were also examined using the non-parametric "classification and regression tree" (CRT) technique for the three diagnostic groups. RESULTS: Nearly all measured parameters were strong enough to distinguish keratoconus. However, only the radius of best fit sphere and keratometry readings had an acceptable predictive accuracy to differentiate subclinical keratoconus. Elevation parameters and surface indices were able to differentiate keratoconus from normal corneas in 100% of eyes. Meanwhile, none of the parameter sets could effectively discriminate subclinical keratoconus; a 3-factor model including keratometric variables, elevation data and surface indices provided the highest predictive ability for this purpose. CONCLUSION: Surface indices measured by the Galilei analyzer can effectively differentiate keratoconus from normal corneas. However, a combination of different data is required to distinguish subclinical keratoconus. PMID- 27195080 TI - Visual, Keratometric and Corneal Biomechanical Changes after Intacs SK Implantation for Moderate to Severe Keratoconus. AB - PURPOSE: To report visual outcomes and corneal biomechanical changes after femtosecond-assisted Intacs SK implantation in keratoconic eyes. METHODS: This prospective interventional case series is comprised of 32 keratoconic eyes of 25 patients with mean age of 23.8 +/- 5.4 years. Uncorrected (UDVA) and corrected (CDVA) distance visual acuity, refraction, manifest refraction spherical equivalent (MRSE), keratometry, central corneal thickness (CCT), corneal hysteresis (CH) and corneal resistance factor (CRF) were measured preoperatively, and 1, 3 and 6 months postoperatively. RESULTS: Mean UDVA improved from 0.81 +/- 0.3 LogMAR preoperatively to 0.53 +/- 0.2 LogMAR six months postoperatively (P < 0.001). At 6 months, MRSE was significantly reduced only in eyes with moderate KCN (mean change, +2.61 +/- 0.54 diopter [D]; P< 0.001). A significant improvement in sphere (mean change, +1.92 +/- 0.37 D; P< 0.001) and mean keratometry (mean change, -3.34 +/- 0.47D; P< 0.001) were observed. CCT increased from 446.1 +/- 38 MUm preoperatively to 462.2 +/- 50 MUm at six months (P < .001). CRF decreased from 6.5 +/- 1.6 mmHg to 5.9 +/- 1.1 mmHg six months after surgery (P = 0.02). CDVA, refractive cylinder and CH did not change significantly (P = 0.48, 0.203 and 0.55, respectively). Linear regression analysis disclosed that a decrease in CCT and moderate KCN are associated with higher CRF (standardized B,-0.513 and 0.314;P= 0.004 and 0.024, respectively; Adjusted R square = 0.353). CONCLUSION: Visual, refractive and keratometric indices remarkably improved in a parallel fashion. CRF was inversely associated with CCT. Changes in CRF represent the trend of changes in corneal biomechanics and thickness during the early postoperative months. PMID- 27195081 TI - MyoRing Implantation in Keratoconic Patients: 3 years Follow-up Data. AB - PURPOSE: To evaluate long-term follow-up data on implantation of a full-ring intra-corneal implant (MyoRing) for management of keratoconus. METHODS: A total of 40 keratoconic eyes of 37 consecutive patients who had undergone MyoRing implantation using the Pocket Maker microkeratome (Dioptex, GmbH, Linz, Austria) and completed 3 years of follow-up appointments were included in this retrospective study. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), refraction and keratometry (K) readings were measured and evaluated preoperatively, and 3 years, postoperatively. RESULTS: No intraoperative complications were observed in this case series. Three years postoperatively, there was a significant improvement in UDVA, CDVA, K readings, spherical equivalent (SE), and manifest sphere and cylinder (P < 0.05 for all comparisons). UDVA was significantly improved from 1.14 +/- 0.27 to 0.30 +/- 0.21 LogMAR (P = 0.001), CDVA was also improved from 0.52 +/- 0.23 to 0.18 +/- 0.12 LogMAR (P = 0.001), SE was decreased by 4.35 diopters (D) and average keratometric values were reduced by 2.34 D (P = 0.001). Overall, 81% of subjects were moderately to highly satisfied 3 years after surgery and 64.90% agreed to have the fellow eye implanted with MyoRing. CONCLUSION: MyoRing implantation using the Pocket Maker microkeratome was found to be a minimally invasive procedure for improving visual acuity and refraction in the majority of the patients with keratoconus. PMID- 27195082 TI - Visual Outcomes of Successful versus Failed Big-Bubble Deep Anterior Lamellar Keratoplasty for Keratoconus. AB - PURPOSE: To compare the visual outcomes of deep anterior lamellar keratoplasty (DALK) for keratoconus with and without successful big-bubble formation. METHODS: In this retrospective comparative study, a total of 289 consecutive eyes from 257 patients underwent DALK using the big-bubble technique. In cases where the big bubble could not be accomplished, manual stromal dissection down to Descemeton membrane (DM) was performed using a crescent knife. Visual acuity and refractive outcomes were compared between the bare DM group (Group 1) and manual dissection group (Group 2). RESULTS: A bare DM was successfully achieved in 229 (79.2%) eyes and manual dissection was performed in 60 (20.8%) eyes. The study groups were comparable in terms of age (P = 0.79), preoperative best-spectacle corrected visual acuity (BSCVA) (P = 0.15), and follow-up duration (P = 0.73). Postoperative BSCVA was significantly better in Group 1 than in Group 2 throughout follow-up (P < 0.05). In Group 2, BSCVA was significantly lower in eyes with advanced keratoconus as compared to those with moderate keratoconus (P = 0.007). At final follow-up, BSCVA <= 0.30 logarithm of minimum angle of resolution (logMAR) was achieved in 82.1% of eyes in Group 1 versus 54.5% of eyes in Group 2 (P < 0.001). Groups 1 and 2 were comparable in terms of postoperative spherical equivalent refractive error (P = 0.61) and keratometric astigmatism (P = 0.39). CONCLUSION: Retention of the posterior corneal stroma which occurs with manual dissection during failed big bubble formation in DALK is associated with lower visual acuity as compared to achieving a bare DM. PMID- 27195083 TI - Long-term Outcomes of Amniotic Membrane Transplantation in Contact Lens-Induced Pseudomonas Keratitis with Impending Corneal Perforation. AB - PURPOSE: To report the anatomical and visual outcomes of double layered amniotic membrane transplantation (AMT) in eyes with advanced Pseudomonas keratitis leading to Descemetocele formation. METHODS: This prospective interventional case series included 6 eyes of 6 female patients with pseudomonas keratitis caused by contact lens-induced infection who underwent double layered AMT. Surgery was performed after the ulcers were found to be poorly responsive to antibiotics, and severe thinning or Descemetocele had developed. All patients underwent a complete examination pre- and postoperatively, as well as anterior segment optical coherence tomography (OCT) and pachymetry or Orbscan after the procedure. RESULTS: Mean follow-up period was 24 months. There was neither frank corneal perforation nor a need for emergent corneal transplantation in any of the eyes. All patients had visual acuity of hand motions before the procedure which improved to 20/50 to 20/30 three months after surgery. No surgical or postoperative complication occurred in this series. CONCLUSION: Double layered AMT may result in acceptable anatomical outcomes in patients with advanced Pseudomonas keratitis with Descemetocele formation and can eliminate the need for emergent corneal transplantation. PMID- 27195084 TI - Diurnal Variations in Intraocular Pressure, Central Corneal Thickness, and Macular and Retinal Nerve Fiber Layer Thickness in Diabetics and Normal Individuals. AB - PURPOSE: To evaluate diurnal variations in intraocular pressure (IOP), central corneal thickness (CCT), and macular and retinal nerve fiber layer (RNFL) thickness in diabetic patients and normal individuals. METHODS: This study included 11 diabetic patients with macular edema and 11 healthy individuals. IOP, CCT, and macular and RNFL thickness were measured every 3 hours on a single day between 9 AM and 6 PM. Diurnal variations in IOP, CCT, total macular volume (TMV), central macular thickness (CMT), average macular thickness (AMT), and RNFL thickness were measured. RESULTS: None of the parameters showed a significant absolute or relative change over the course of the day. However, the following non-significant changes were observed. In the control group, all parameters demonstrated the highest values at 9 AM. The lowest IOP, TMV and AMT occurred at 12 PM; lowest CCT and RNFL at 6 PM; and the lowest CMT at 3 PM. Diabetic subjects had the highest values of RNFL, CMT and TMV at 9 AM, and that for IOP, CCT and AMT at 6 PM. The lowest RNFL and CMT values occurred at 6 PM; lowest IOP at 12 PM; and the lowest CCT, TMV and AMT were observed at 3 PM. In the diabetic group, TMV, CMT, AMT and CCT were significantly higher and RNFL was significantly lower than the control group at all time points (all P- values < 0.05). CONCLUSION: While there were slight decreases in IOP, RNFL thickness and CMT during the day, these changes were not significant between 9 AM and 6 PM and probably do not affect the interpretation of measurements. PMID- 27195085 TI - Clinical Features and Risk Factors of Patients with Presumed Ocular Toxoplasmosis. AB - PURPOSE: To determine the clinical features and risk factors of presumed ocular toxoplasmosis (POT) in patients affected with the condition at Irrua, Nigeria. METHODS: The study included 69 patients with POT, and 69 age and sex matched subjects who served as the control group. Data was obtained using interviewer administered questionnaires. Examination included measurement of visual acuity (VA), intraocular pressure (IOP), slit lamp examination, gonioscopy and dilated fundus examination. RESULTS: Mean age of cases and control subjects was 57.16 +/- 18.69 and 56.09 +/- 16.01 years respectively. The peak age group in patients with POT was 60 years and above. The most common presenting complaint was blurred vision occurring in 100% of cases. Drinking unfiltered water in 58 (84.1%) patients was the most common risk factor. Other risk factors included post cataract surgery status in 32 (46.4%) subjects, ingestion of poorly cooked meat in 30 (43.5%) cases and exposure to cats in 9 (13.0%) patients. All risk factors were more common in POT patients (P < 0.05). Out of 69 patients, 62 (89.9%) had unilateral while 7 (10.1%) had bilateral involvement. Out of 76 eyes with uveitis, 53 (69.7%) were blind. Active disease was significantly more common with increasing age (P < 0.05). CONCLUSION: Patients with POT were rather old and some risk factors were modifiable, therefore health education for preventing the transmission of toxoplasmosis and provision of sanitary water may help reduce the incidence of ocular toxoplasmosis. PMID- 27195087 TI - Intravitreal Bevacizumab for Treatment of Central Serous Chorioretinopathy. AB - PURPOSE: To compare the outcomes of treatment with intravitreal bevacizumab (IVB) versus observation in central serous chorioretinopathy (CSCR). METHODS: In a retrospective comparative study, records of 45 patients with CSCR were reviewed. Twenty-two patients received IVB (1.25 mg/0.05 ml) while 23 subjects were observed. All subjects underwent measurement of best corrected visual acuity (BCVA) and intraocular pressure (IOP), dilated fundus examination and optical coherence tomography (OCT) imaging at baseline and follow up visits. Outcome measures included central macular thickness (CMT) and BCVA in logarithm of minimum angle of resolution (logMAR) notations. RESULTS: Mean age was 44.1 +/- 9.3 (range: 24 to 64) years and mean follow-up period was 10.4 +/- 11.2 (range: 3 to 43; median: 6) months. All patients demonstrated resolution of neurosensory detachment and improvement in visual acuity. At final visit, there was no significant difference in mean CMT between the IVB and observation groups (275 vs 284 MUm, P> 0.05). Mean baseline logMAR visual acuity was 0.38 +/- 0.24 in the IVB group which improved to 0.24 +/- 0.31 at final follow-up (P = 0.011); mean baseline logMAR visual acuity was 0.42 +/- 0.28 in the observation group and improved to 0.12 +/- 0.18 (P = 0.001). Visual improvement was more marked in the observation group (0.30 vs 0.14 logMAR, P< 0.05) and mean final visual acuity was also significantly better (P = 0.05). CONCLUSION: There was no significant difference between IVB injection and observation in terms of anatomical outcomes of treatment for CSCR. In terms of visual outcomes, observation was superior to IVB injection. PMID- 27195086 TI - Association of Age Related Macular Degeneration and Age Related Hearing Impairment. AB - PURPOSE: To evaluate the association between age-related macular degeneration (ARMD) and sensory neural hearing impairment (SHI). METHODS: In this case-control study, hearing status of 46 consecutive patients with ARMD were compared with 46 age-matched cases without clinical ARMD as a control group. In all patients, retinal involvements were confirmed by clinical examination, fluorescein angiography (FA) and optical coherence tomography (OCT). All participants were examined with an otoscope and underwent audiological tests including pure tone audiometry (PTA), speech reception threshold (SRT), speech discrimination score (SDS), tympanometry, reflex tests and auditory brainstem response (ABR). RESULTS: A significant (P = 0.009) association was present between ARMD, especially with exudative and choroidal neovascularization (CNV) components, and age-related hearing impairment primarily involving high frequencies. Patients had higher SRT and lower SDS against anticipated presbycusis than control subjects. Similar results were detected in exudative, CNV and scar patterns supporting an association between late ARMD with SRT and SDS abnormalities. ABR showed significantly prolonged wave I and IV latency times in ARMD (P = 0.034 and 0.022, respectively). Average latency periods for wave I in geographic atrophy (GA) and CNV, and that for wave IV in drusen patterns of ARMD were significantly higher than controls (P = 0.030, 0.007 and 0.050, respectively). CONCLUSION: The association between ARMD and age-related SHI may be attributed to common anatomical components such as melanin in these two sensory organs. PMID- 27195088 TI - Half-dose Photodynamic Therapy for Chronic Central Serous Chorioretinopathy. AB - PURPOSE: To report the outcomes of half-dose photodynamic therapy (PDT) in patients with chronic central serous chorioretinopathy (CSC). METHODS: A chart review of patients with chronic CSC who had received half-dose verteporfin PDT (3 mg/m(2)) was performed. The main outcome measures were resolution of subretinal fluid and best corrected visual acuity (BCVA). RESULTS: Fifty-three eyes of 51 patients with mean age of 45.01 +/- 8.9 years were studied. Three, 6 and 12 months after half-dose PDT, subretinal fluid was completely resolved in 51 eyes (96.2%). In 2 eyes (one patient), subretinal fluid decreased at 3 months but one year later, an increase in subretinal fluid was detected on optical coherence tomography (OCT) which completely resolved following additional PDT. Another patient with recurrence of subretinal fluid rejected further treatment. Mean baseline central subfield thickness was 385 +/- 113.0 MUm which was decreased to 235 +/- 39.7, 247 +/- 49.7, and 244 +/- 49.52 MUm after 3, 6 and 12 months, respectively (all P-values < 0.001). Mean BCVA was 0.33 +/- 0.27 LogMAR before PDT and 0.11 +/- 0.18, 0.11 +/- 0.17, 0.17 +/- 0.26 and 0.10 +/- 0.23 LogMAR, 3, 6 and 12 months and at final visit (up to 60 months) after PDT, respectively (all P-values < 0.001). Improvement >=2 lines in BCVA occurred in 20 eyes (37.7%). Statistically significant correlations were found between improvement in BCVA and baseline BCVA, baseline central subfield thickness and central subfield thickness after resorption of subretinal fluid (P < 0.001, P= 0.04 and P= 0.01, respectively). No complications attributed to PDT were observed. CONCLUSION: Half dose PDT is effective for treatment of patients with chronic CSC. PMID- 27195089 TI - Histological and Electrophysiological Changes in the Retinal Pigment Epithelium after Injection of Sodium Iodate in the Orbital Venus Plexus of Pigmented Rats. AB - PURPOSE: To characterize histopathologic and electroretinographic (ERG) changes in the retina of pigmented rats injected with sodium iodate in order to establish a model of retinal degeneration for future cell therapy studies. METHODS: In 50 male pigmented rats weighing 250-300 grams, NaIO3 was injected into the left orbital venous plexus at 40 and 60 mg/kg doses (25 eyes in each group). Fourteen rats received phosphate buffered saline (PBS) injection in their left orbital plexus and were considered as the sham-control group. Histopathologic and ERG studies were performed at baseline and on days 1, 7, 14 and 28 after the injections. RESULTS: Progressive retinal pigment epithelial (RPE) changes were observed from the first day of injection in both the 40 and 60 mg/kg study groups in a dose dependent manner. These changes manifested as loss of melanin pigment and accumulation of lipofuscin in RPE cells with subsequent cell death and patchy loss of RPE cells (in flat mounts), as well as thinning of the outer nuclear layer and later the inner nuclear layer in the succeeding days. ERG showed a progressive and significant decrease in a- and b- wave amplitudes in both case groups relative to baseline values and the controls (P < 0.05). CONCLUSION: NaIO3 injection into the retrobulbar venous plexus of pigmented rats can result in significant and progressive damage to the RPE and subsequently to the neuroretina of the injected eye, and may serve as a model of retinal degeneration. PMID- 27195090 TI - Ocular Health and Safety Assessment among Mechanics of the Cape Coast Metropolis, Ghana. AB - PURPOSE: To conduct an ocular health and safety assessment among mechanics in the Cape Coast Metropolis, Ghana. METHODS: This descriptive cross sectional study included 500 mechanics using multistage sampling. All participants filled a structured questionnaire on demographic data, occupational history and ocular health history. Study participants underwent determination of visual acuity (VA) using LogMAR chart, external eye examination with a handheld slit lamp biomicroscope, dilated fundus examination, applanation tonometry and refraction. RESULTS: Out of 500 mechanics, 433 were examined (response rate, 87%) comprised of 408 (94.2%) male and 25 (5.8%) female subjects. The prevalence of visual impairment (i.e. presenting VA < 6/18) among the respondents was 2.1%. Eye injuries were reported in 171 (39.5%) mechanics probably due to the large number of workers, 314 (72.5%), who did not use eye protective devices. Mechanics in the auto welding category were at the highest risk of sustaining an eye injury (odds ratio [OR], 13.4; P < 0.001). Anterior segment ocular disorders were mostly pterygia while posterior segment eye disorders included glaucoma suspects and retinochoroidal lesions. The development of pterygia was associated with the number of years a mechanic stayed on the job. Eye care seeking behavior among the participants was poor. CONCLUSION: Eye injuries were prevalent among the mechanics as the use of eye protection was low. Eye safety should be made an integral part of the public health agenda in the Cape Coast Metropolis. PMID- 27195091 TI - Optical Coherence Tomography Angiography in Retinal Diseases. AB - Optical coherence tomography angiography (OCTA) is a new, non-invasive imaging system that generates volumetric data of retinal and choroidal layers. It has the ability to show both structural and blood flow information. Split-spectrum amplitude-decorrelation angiography (SSADA) algorithm (a vital component of OCTA software) helps to decrease the signal to noise ratio of flow detection thus enhancing visualization of retinal vasculature using motion contrast. Published studies describe potential efficacy for OCTA in the evaluation of common ophthalmologic diseases such as diabetic retinopathy, age related macular degeneration (AMD), retinal vascular occlusions and sickle cell disease. OCTA provides a detailed view of the retinal vasculature, which allows accurate delineation of microvascular abnormalities in diabetic eyes and vascular occlusions. It helps quantify vascular compromise depending upon the severity of diabetic retinopathy. OCTA can also elucidate the presence of choroidal neovascularization (CNV) in wet AMD. In this paper, we review the knowledge, available in English language publications regarding OCTA, and compare it with the conventional angiographic standard, fluorescein angiography (FA). Finally, we summarize its potential applications to retinal vascular diseases. Its current limitations include a relatively small field of view, inability to show leakage, and tendency for image artifacts. Further larger studies will define OCTA's utility in clinical settings and establish if the technology may offer a non invasive option of visualizing the retinal vasculature, enabling us to decrease morbidity through early detection and intervention in retinal diseases. PMID- 27195092 TI - Surgery for Proliferative Diabetic Retinopathy: New Tips and Tricks. AB - Over the recent years, retina specialists have enjoyed significant improvements in the surgical management of proliferative diabetic retinopathy including improved preoperative planning, vitreoretinal instrumentation and new surgical maneuvers. In this review, we present new tips and tricks such as preoperative pharmacotherapy approaches including pegaptanib injection and biodegradable dexamethasone implantation, bimanual vitrectomy techniques and the concept of mixing small gauges as well as valved cannulas and intraoperative optical coherence tomography. With advanced surgical planning and sophisticated operative maneuvers tailored to the individual patient, excellent outcomes can be achieved even in severe cases of diabetic tractional detachment. PMID- 27195093 TI - Macula-Sparing Rhegmatogenous Retinal Detachment: Is Emergent Surgery Necessary? AB - The status of the macula is a significant factor in determining final visual outcomes in rhegmatogenous retinal detachment (RRD) and should be considered in the timing of surgical repair. Several studies have shown that macula-involving RRDs attain similar visual and anatomic outcomes when surgery is performed within seven days as compared to emergent surgery (within 24 hours). In contrast, surgery prior to macular detachment in macula-sparing RRDs generally yields the best visual outcomes. In the case of macula-sparing RRDs, it is not clear how long the macula may remain attached, therefore, standard practice dictates emergent surgery. Timing of presentation, examination findings, case complexity, co-existing medical conditions, surgeon expertise, and timing and quality of access to operating facilities and staff, however, should all be considered in determining whether a macula-sparing RRD requires immediate intervention or if equivalent visual and possibly better overall outcomes can be achieved with scheduled surgery within an appropriate time frame. PMID- 27195094 TI - Recurrent Corneal Perforation due to Chronic Graft versus Host Disease; a Clinicopathologic Report. AB - PURPOSE: To describe a case of chronic graft versus host disease (GVHD) leading to severe dry eye and recurrent corneal perforation in both eyes, its stepwise management and histopathological reports. CASE REPORT: A 22-year-old woman with a history of thalassemia and subsequent high-dose chemotherapy followed by allogeneic bone marrow transplant (BMT) was referred to Farabi Eye Hospital. Despite aggressive medical and surgical intervention, corneal vascularization in her right eye progressed and led to corneal perforation. Cyanoacrylate glue was applied to seal the perforation, however it recurred. Multilayer amniotic membrane transplantation (AMT) was performed to seal the corneal perforation, which was effective for a short period. Subsequently, the corneal perforation recurred and penetrating keratoplasty was performed. After a few months deep vascularization and descemetocele occurred in the fellow left eye and the patient finally underwent therapeutic lamellar keratoplasty. CONCLUSION: Patients with GVHD are at risk of severe dry eye and subsequent corneal vascularization. Recurrent and recalcitrant corneal perforation resistant to cyanoacrylate glue and multilayer AMT may occur. Proper systemic and ocular management alongside close collaboration with the hematologist is strongly recommended to control the condition. PMID- 27195095 TI - Wound Dehiscence and Device Migration after Subconjunctival Bevacizumab Injection with Ahmed Glaucoma Valve Implantation. AB - PURPOSE: To report a complication pertaining to subconjunctival bevacizumab injection as an adjunct to Ahmed Glaucoma Valve (AGV) implantation. CASE REPORT: A 54-year-old woman with history of complicated cataract surgery was referred for advanced intractable glaucoma. AGV implantation with adjunctive subconjunctival bevacizumab (1.25 mg) was performed with satisfactory results during the first postoperative week. However, 10 days after surgery, she developed wound dehiscence and tube exposure. The second case was a 33-year-old man with history of congenital glaucoma and uncontrolled IOP who developed AGV exposure and wound dehiscence after surgery. In both cases, for prevention of endophthalmitis and corneal damage by the unstable tube, the shunt was removed and the conjunctiva was re-sutured. CONCLUSION: The potential adverse effect of subconjunctival bevacizumab injection on wound healing should be considered in AGV surgery. PMID- 27195096 TI - Successful Management of Diffuse Unilateral Subacute Neuroretinitis with Anthelmintics, and Intravitreal Triamcinolone followed by Laser Photocoagulation. AB - PURPOSE: Diffuse unilateral subacute neuroretinitis (DUSN), a form of posterior uveitis, is secondary to the presence of a highly motile nematode in the intraretinal or subretinal space. Herein, we report a case of DUSN that was successfully managed by an intravitreal injection of triamcinolone and laser therapy. CASE REPORT: A middle-aged man with complaint of decreased vision and marked unilateral vitritis and neuroretinitis. Fluorescein angiography revealed disc leakage, vessel wall staining, and diffuse track-like transmission defects of the RPE. Optical coherence tomography confirmed the subretinal location of the worm. The patient received oral thiabendazole and an intravitreal injection of triamcinolone acetonide. After 10 days, media haziness decreased, and a live motile subretinal worm was identified. Direct laser photocoagulation was performed to destroy the worm. After two months, a localized chorioretinal scar developed and no further active inflammation and subretinal worms were detected. CONCLUSION: Intravitreal steroids can be used safely in cases with DUSN and may help detect the causative worm for applying laser photocoagulation. PMID- 27195097 TI - Pigmentary Glaucoma with Retinochoroidal Pigmentation. PMID- 27195098 TI - High Myopic Peripapillary Atrophy; Spectral Domain Optical Coherence Tomography Features. PMID- 27195099 TI - The Effect of Intravenous Conivaptan on Intraocular Pressure. PMID- 27195100 TI - Increased Waist-to-height Ratio May Contribute to Age-related Increase in Cardiovascular Risk Factors. AB - BACKGROUND: The risk of cardiovascular diseases (CVDs) increases with age. The objective was to determine whether lifestyle and dietary behaviors and anthropometric measures, which are affected by these behaviors, contribute to the increase of CVD risk factors across age categories of 20-50-year-old. METHODS: In a cross-sectional design, 437 adults aged 20-50-year-old were selected from households living in Shiraz. Risk factors of CVD, including body mass index (BMI), waist-to-height ratio (WHtR), blood pressure, fasting blood glucose (FBG), serum triglycerides, total cholesterol, and low- and high-density lipoprotein cholesterol (LDL-C and HDL-C, respectively) as well as lifestyle behaviors (physical activity and smoking), dietary habits, and food intakes were assessed across the age categories of 20-29, 30-39, and 40-50 years. Linear regression was used to examine the contribution of different variables to the age-related increase of CVD risk factors. RESULTS: All CVD risk factors, except for HDL-C, significantly increased across age categories. Older subjects had healthier dietary habits and food intakes, but they possessed nonsignificantly lower physical activity and higher smoking rate compared to younger adults. Adjusting for physical activity, smoking, and BMI did not change the significant positive association between age and CVD risk factors but adjusting for WHtR disappeared associations for blood pressure, triglycerides, and metabolic syndrome although significant associations remained for FBG and total and LDL-C. CONCLUSIONS: Age related increase of CVD risk factors occurred independent of lifestyle habits. WHtR, but not BMI, may partially contribute to the age-related increase in CVD risk factors. PMID- 27195101 TI - Development and Psychometric Evaluation of a Health Action Process Approach Inventory for Healthful Diet Among Type 2 Diabetes Patients. AB - BACKGROUND: Long-term effects of diabetes could be prevented or delayed by adopting a proper diet. The aim of this study was to adapt and provide a pilot test using health action process approach (HAPA)-based inventory to capable of capturing significant determinants of healthful diet for diabetics. METHODS: The inventory was reviewed by eight diabetes patients and verbal feedbacks with regard the comprehension, item relevance, and potential new content were obtained. Then, the inventory items were evaluated by an expert panel. Next exploratory factor analysis (EFA) was conducted to assess the scale constructs. Criterion validity was measured by Pearson correlation. Finally, reliability measures of internal consistency and test-retest analysis were determined. RESULTS: A total of 121 diabetic patients participated in this study. EFA extracted seven factors (risk-perception, action self-efficacy, outcome expectancies, maintenance self-efficacy, action and coping planning, behavioral intention, and recovery self-efficacy) explaining 81.14% of the total variance. There were significant correlations between behavioral intentions and both outcome expectancies (r = 0.55, P < 0.05) and action self-efficacy (r = 0.31, P < 0.004) and small to moderate correlations (rs = 23-40) between behavior and the volitional constructs of the HAPA model. Cronbach's alpha ranging from 0.65 to 0.95 and intraclass correlation coefficients ranging from 0.71 to 0.92 indicated an acceptable internal consistency. CONCLUSIONS: Developed scales were valid and reliable for measuring HAPA variables to be used with type 2 diabetes mellitus patients. Further examination with minority persons is warranted. PMID- 27195102 TI - The cellular microscopy phenotype ontology. AB - BACKGROUND: Phenotypic data derived from high content screening is currently annotated using free-text, thus preventing the integration of independent datasets, including those generated in different biological domains, such as cell lines, mouse and human tissues. DESCRIPTION: We present the Cellular Microscopy Phenotype Ontology (CMPO), a species neutral ontology for describing phenotypic observations relating to the whole cell, cellular components, cellular processes and cell populations. CMPO is compatible with related ontology efforts, allowing for future cross-species integration of phenotypic data. CMPO was developed following a curator-driven approach where phenotype data were annotated by expert biologists following the Entity-Quality (EQ) pattern. These EQs were subsequently transformed into new CMPO terms following an established post composition process. CONCLUSION: CMPO is currently being utilized to annotate phenotypes associated with high content screening datasets stored in several image repositories including the Image Data Repository (IDR), MitoSys project database and the Cellular Phenotype Database to facilitate data browsing and discoverability. PMID- 27195104 TI - Adaptive genetic variation distinguishes Chilean blue mussels (Mytilus chilensis) from different marine environments. AB - Chilean mussel populations have been thought to be panmictic with limited genetic structure. Genotyping-by-sequencing approaches have enabled investigation of genomewide variation that may better distinguish populations that have evolved in different environments. We investigated neutral and adaptive genetic variation in Mytilus from six locations in southern Chile with 1240 SNPs obtained with RAD seq. Differentiation among locations with 891 neutral SNPs was low (FST = 0.005). Higher differentiation was obtained with a panel of 58 putative outlier SNPs (FST = 0.114) indicating the potential for local adaptation. This panel identified clusters of genetically related individuals and demonstrated that much of the differentiation (~92%) could be attributed to the three major regions and environments: extreme conditions in Patagonia, inner bay influenced by aquaculture (Reloncavi), and outer bay (Chiloe Island). Patagonia samples were most distinct, but additional analysis carried out excluding this collection also revealed adaptive divergence between inner and outer bay samples. The four locations within Reloncavi area were most similar with all panels of markers, likely due to similar environments, high gene flow by aquaculture practices, and low geographical distance. Our results and the SNP markers developed will be a powerful tool supporting management and programs of this harvested species. PMID- 27195103 TI - Age and sex dependent effects of early overnutrition on metabolic parameters and the role of neonatal androgens. AB - BACKGROUND: Males and females respond differently to diverse metabolic situations. Being raised in a small litter is reported to cause overnutrition that increases weight gain and predisposes an individual to metabolic disturbances in adulthood; however, existing data are inconsistent. Indeed, significant weight gain and/or metabolic disturbances, such as hyperinsulinemia and hyperleptinemia, are sometimes not encountered. We hypothesized that these inconsistencies could be due to the animal's sex and/or age at which metabolic parameters are measured. METHODS: To analyze the effects of neonatal overnutrition, male and female Wistar rats were raised in litters of 4 or 12 pups/dam and killed at postnatal days (PND) 10, 21, 30, 50, 85, or 150. In a second study to determine if neonatal sex steroid levels influence sex differences in metabolic parameters, female rats were treated with testosterone on PND1. Effects on weight, length, fat pads, adipokine production, and serum levels of glucose, metabolic hormones, and cytokines were analyzed in both studies. RESULTS: By PND10, both males and females raised in small litters had increased body weight, body length, adiposity, and serum glucose, insulin, leptin, and adiponectin levels. Females had a greater increase in inguinal fat, and males had higher expression of leptin messenger RNA (mRNA) and serum insulin, as well as increased testosterone levels. Most of the litter size effects diminished or disappeared after weaning and reappeared during adulthood in males, with sex differences in body size and adiposity being apparent postpubertally. Treatment of females with testosterone on PND1 tended to masculinize some metabolic parameters in adulthood such as increased body weight and serum leptin levels. CONCLUSIONS: Our results indicate that (1) both sex and age determine the response to neonatal overnutrition; (2) differences in neonatal sex steroid levels may participate in the development of sex differences in metabolic parameters in adulthood and possibly in the response to neonatal overnutrition; and (3) the comparison of circulating hormone and cytokine levels, even in normal control animals, should take into consideration the early neonatal nutritional environment. PMID- 27195105 TI - Temperature and population density: interactional effects of environmental factors on phenotypic plasticity, immune defenses, and disease resistance in an insect pest. AB - Temperature and crowding are key environmental factors mediating the transmission and epizooty of infectious disease in ectotherm animals. The host physiology may be altered in a temperature-dependent manner and thus affects the pathogen development and course of diseases within an individual and host population, or the transmission rates (or infectivity) of pathogens shift linearly with the host population density. To our understanding, the knowledge of interactive and synergistic effects of temperature and population density on the host-pathogen system is limited. Here, we tested the interactional effects of these environmental factors on phenotypic plasticity, immune defenses, and disease resistance in the velvetbean caterpillar Anticarsia gemmatalis. Upon egg hatching, caterpillars were reared in thermostat-controlled chambers in a 2 * 4 factorial design: density (1 or 8 caterpillars/pot) and temperature (20, 24, 28, or 32 degrees C). Of the immune defenses assessed, encapsulation response was directly affected by none of the environmental factors; capsule melanization increased with temperature in both lone- and group-reared caterpillars, although the lone-reared ones presented the most evident response, and hemocyte numbers decreased with temperature regardless of the population density. Temperature, but not population density, affected considerably the time from inoculation to death of velvetbean caterpillar. Thus, velvetbean caterpillars succumbed to Anticarsia gemmatalis multiple nucleopolyhedrovirus (AgMNPV) more quickly at higher temperatures than at lower temperatures. As hypothesized, temperature likely affected caterpillars' movement rates, and thus the contact between conspecifics, which in turn affected the phenotypic expression of group-reared caterpillars. Our results suggest that environmental factors, mainly temperature, strongly affect both the course of disease in velvetbean caterpillar population and its defenses against pathogens. As a soybean pest, velvetbean caterpillar may increase its damage on soybean fields under a scenario of global warming as caterpillars may reach the developmental resistance faster, and thus decrease their susceptibility to biological control by AgMNPV. PMID- 27195107 TI - Recommendations for open data science. AB - Life science research increasingly relies on large-scale computational analyses. However, the code and data used for these analyses are often lacking in publications. To maximize scientific impact, reproducibility, and reuse, it is crucial that these resources are made publicly available and are fully transparent. We provide recommendations for improving the openness of data-driven studies in life sciences. PMID- 27195106 TI - Introducing BASE: the Biomes of Australian Soil Environments soil microbial diversity database. AB - BACKGROUND: Microbial inhabitants of soils are important to ecosystem and planetary functions, yet there are large gaps in our knowledge of their diversity and ecology. The 'Biomes of Australian Soil Environments' (BASE) project has generated a database of microbial diversity with associated metadata across extensive environmental gradients at continental scale. As the characterisation of microbes rapidly expands, the BASE database provides an evolving platform for interrogating and integrating microbial diversity and function. FINDINGS: BASE currently provides amplicon sequences and associated contextual data for over 900 sites encompassing all Australian states and territories, a wide variety of bioregions, vegetation and land-use types. Amplicons target bacteria, archaea and general and fungal-specific eukaryotes. The growing database will soon include metagenomics data. Data are provided in both raw sequence (FASTQ) and analysed OTU table formats and are accessed via the project's data portal, which provides a user-friendly search tool to quickly identify samples of interest. Processed data can be visually interrogated and intersected with other Australian diversity and environmental data using tools developed by the 'Atlas of Living Australia'. CONCLUSIONS: Developed within an open data framework, the BASE project is the first Australian soil microbial diversity database. The database will grow and link to other global efforts to explore microbial, plant, animal, and marine biodiversity. Its design and open access nature ensures that BASE will evolve as a valuable tool for documenting an often overlooked component of biodiversity and the many microbe-driven processes that are essential to sustain soil function and ecosystem services. PMID- 27195109 TI - Osteoimmunology: from mice to humans. AB - The immune system has been recognized as one of the most important regulators of bone turnover and its deregulation is implicated in several bone diseases such as postmenopausal osteoporosis and inflammatory bone loss; recently it has been suggested that the gut microbiota may influence bone turnover by modulation of the immune system. The study of the relationship between the immune system and bone metabolism is generally indicated under the term 'osteoimmunology'. The vast majority of these studies have been performed in animal models; however, several data have been confirmed in humans as well: this review summarizes recent data on the relationship between the immune system and bone with particular regard to the data confirmed in humans. PMID- 27195108 TI - How to interpret epigenetic association studies: a guide for clinicians. AB - Epigenetic mechanisms are able to alter gene expression, without altering DNA sequence, in a stable manner through cell divisions. They include, among others, the methylation of DNA cytosines and microRNAs and allow the cells to adapt to changing environmental conditions. In recent years, epigenetic association studies are providing new insights into the pathogenesis of complex disorders including prevalent skeletal disorders. Unlike the genome, the epigenome is cell and tissue specific and may change with age and a number of acquired factors. This poses particular difficulties for the design and interpretation of epigenetic studies, particularly those exploring the association of genome-wide epigenetic marks with disease phenotypes. In this report, we propose a framework to help in the critical appraisal of epigenetic association studies. In line with previous suggestions, we focus on the questions critical to appraise the validity of the study, to interpret the results and to assess the generalizability and relevance of the information. PMID- 27195110 TI - Human lymph-node CD8(+) T cells display an altered phenotype during systemic autoimmunity. AB - Although many studies are focused on auto-reactive CD4(+) T cells, the precise role of CD8(+) T cells in autoimmunity is poorly understood. The objective of this study is to provide more insight into the phenotype and function CD8(+) T cells during the development of autoimmune disease by studying CD8(+) T cells in human lymph-node biopsies and peripheral blood obtained during the earliest phases of rheumatoid arthritis (RA). Here, we show that lymphoid pro-inflammatory CD8(+) T cells exhibit a less-responsive phenotype already during the earliest phases of autoimmunity compared with healthy individuals. We found an increase in CD8(+) memory T cells in lymphoid tissue during the earliest phases of autoimmunity, even before clinical onset of RA, accompanied by an increased frequency of non-circulating or recently activated (CD69(+)) CD8(+) T cells in lymphoid tissue and peripheral blood. Importantly, lymphoid pro-inflammatory CD8(+)IL-17A(+) T cells displayed a decreased capacity of cytokine production, which was related to disease activity in early RA patients. In addition, a decreased frequency of regulatory CD8(+)IL-10(+) T cells in peripheral blood was also related to disease activity in early RA patients. Our results suggest that different CD8(+) T-cell subsets are affected already during the earliest phases of systemic autoimmunity. PMID- 27195111 TI - A multi-laboratory comparison of blood dendritic cell populations. AB - HLDA10 collated a panel of monoclonal antibodies (mAbs) that primarily recognised molecules on human myeloid cell and dendritic cell (DC) populations. As part of the studies, we validated a backbone of mAbs to delineate monocyte and DC populations from peripheral blood. The mAb backbone allowed identification of monocyte and DC subsets using fluorochromes that were compatible with most 'off the shelf' or routine flow cytometers. Three laboratories used this mAb backbone to assess the HLDA10 panel on blood monocytes and DCs. Each laboratory was provided with enough mAbs to perform five repeat experiments. The data were collated and analysed using Spanning-tree Progression Analysis of Density normalised Events (SPADE). The data were interrogated for inter- and intra laboratory variability. The results highlight the definition of DC populations using current readily available reagents. This collaborative process provides the broader scientific community with an invaluable data set that validates mAbs to leucocyte surface molecules. PMID- 27195113 TI - OX40, PD-1 and CTLA-4 are selectively expressed on tumor-infiltrating T cells in head and neck cancer. AB - The tumor microenvironment of squamous cell carcinoma of the head and neck (SCCHN) has been shown to be immune suppressive. Therefore, strategies aimed at overcoming this issue could have a positive therapeutic impact. Hence, we investigated the expression of the known immune-modulatory proteins OX40, programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) in SCCHN on different T-cell subsets of tumor-infiltrating lymphocytes (TIL) to ascertain whether these proteins could potentially be targeted alone or in combination for future clinical trials. T cells from peripheral blood (PBL) and tumor were analyzed for the expression of OX40, PD-1 and CTLA-4 in 29 patients undergoing surgery. These proteins were all expressed significantly higher in T-cell subsets isolated from tumors compared with PBL of the same patient. OX40 expression was significantly greater in the TIL regulatory T-cell (Treg) population relative to conventional CD4 and CD8 TIL or the Treg isolated from PBL. PD-1 expression was increased in all T-cell subsets relative to PBL. CTLA-4 was also increased in all TIL subsets relative to blood, and similar to OX40, its highest level of expression was observed in the Treg TIL. The highest frequency of PD-1, CTLA-4 and OX40 triple-positive cells were found in the Treg population isolated from the tumor. We analyzed both human papilloma virus-positive and -negative patients and found similar levels and expression patterns of these two patient populations for all three proteins. These data suggest that there may be therapeutic advantages of targeting these pathways independently or in combination for patients with this disease. PMID- 27195112 TI - Synthetic glycolipid activators of natural killer T cells as immunotherapeutic agents. AB - Certain types of glycolipids have been found to have remarkable immunomodulatory properties as a result of their ability to activate specific T lymphocyte populations with an extremely wide range of immune effector properties. The most extensively studied glycolipid reactive T cells are known as invariant natural killer T (iNKT) cells. The antigen receptors of these cells specifically recognize certain glycolipids, most notably glycosphingolipids with alpha anomeric monosaccharides, presented by the major histocompatibility complex class I-like molecule CD1d. Once activated, iNKT cells can secrete a very diverse array of pro- and anti-inflammatory cytokines to modulate innate and adaptive immune responses. Thus, glycolipid-mediated activation of iNKT cells has been explored for immunotherapy in a variety of disease states, including cancer and a range of infections. In this review, we discuss the design of synthetic glycolipid activators for iNKT cells, their impact on adaptive immune responses and their use to modulate iNKT cell responses to improve immunity against infections and cancer. Current challenges in translating results from preclinical animal studies to humans are also discussed. PMID- 27195114 TI - The cell surface environment for pathogen recognition and entry. AB - The surface of mammalian cells offers an interface between the cell interior and its surrounding milieu. As part of the innate immune system, macrophages have cell surface features optimised for probing and sampling as they patrol our tissues for pathogens, debris or dead cells. Their highly dynamic and constantly moving cell surface has extensions such as lamellipodia, filopodia and dorsal ruffles that help detect pathogens. Dorsal ruffles give rise to macropinosomes for rapid, high volume non-selective fluid sampling, receptor internalisation and plasma membrane turnover. Ruffles can also generate phagocytic cups for the receptor-mediated uptake of pathogens or particles. The membrane lipids, actin cytoskeleton, receptors and signalling proteins that constitute these cell surface domains are discussed. Although the cell surface is designed to counteract pathogens, many bacteria, viruses and other pathogens have evolved to circumvent or hijack these cell structures and their underlying machinery for entry and survival. Nevertheless, these features offer important potential for developing vaccines, drugs and preventative measures to help fight infection. PMID- 27195116 TI - Regulation of immune cell function by short-chain fatty acids. AB - Short-chain fatty acids (SCFAs) are bacterial fermentation products, which are chemically composed by a carboxylic acid moiety and a small hydrocarbon chain. Among them, acetic, propionic and butyric acids are the most studied, presenting, respectively, two, three and four carbons in their chemical structure. These metabolites are found in high concentrations in the intestinal tract, from where they are uptaken by intestinal epithelial cells (IECs). The SCFAs are partially used as a source of ATP by these cells. In addition, these molecules act as a link between the microbiota and the immune system by modulating different aspects of IECs and leukocytes development, survival and function through activation of G protein coupled receptors (FFAR2, FFAR3, GPR109a and Olfr78) and by modulation of the activity of enzymes and transcription factors including the histone acetyltransferase and deacetylase and the hypoxia-inducible factor. Considering that, it is not a surprise, the fact that these molecules and/or their targets are suggested to have an important role in the maintenance of intestinal homeostasis and that changes in components of this system are associated with pathological conditions including inflammatory bowel disease, obesity and others. The aim of this review is to present a clear and updated description of the effects of the SCFAs derived from bacteria on host immune system, as well as the molecular mechanisms involved on them. PMID- 27195117 TI - Local innate immune responses in the vaccine adjuvant-injected muscle. AB - Inducing a high magnitude of antibodies, possibly in combination with T-cell responses that offer epitope breadth over prolonged periods of time is likely a prerequisite for effective vaccines against severe diseases such as HIV-1 infection, malaria and tuberculosis. A much better understanding of the innate immune mechanisms that are critical for inducing desired responses to vaccination would help in the design of novel vaccines. The majority of human vaccines are administered into the muscle. In this brief review, we focus on the initial innate immune events that occur locally at the site of intramuscular vaccine delivery, and how they are influenced by clinically approved vaccine adjuvants. In particular, the effects on cell mobilization, cell activation and vaccine antigen uptake are reviewed. Understanding how distinct adjuvants enhance and tailor vaccine responses would facilitate the selection of the best-suited adjuvant to improve vaccine efficacy to a given pathogen. PMID- 27195115 TI - Bugging inflammation: role of the gut microbiota. AB - The advent of vaccination and improved hygiene have eliminated many of the deadly infectious pathogens in developed nations. However, the incidences of inflammatory diseases, such as inflammatory bowel disease, asthma, obesity and diabetes are increasing dramatically. Research in the recent decades revealed that it is indeed the lack of early childhood microbial exposure, increase use of antibiotics, as well as increase consumption of processed foods high in carbohydrates and fats, and lacking fibre, which wreak havoc on the proper development of immunity and predispose the host to elevated inflammatory conditions. Although largely unexplored and under-appreciated until recent years, these factors impact significantly on the composition of the gut microbiota (a collection of microorganisms that live within the host mucosal tissue) and inadvertently play intricate and pivotal roles in modulating an appropriate host immune response. The suggestion that shifts in the composition of host microbiota is a risk factor for inflammatory disease raises an exciting opportunity whereby the microbiota may also present as a potential modifiable component or therapeutic target for inflammatory diseases. This review provides insights into the interactions between the microbiota and the immune system, how these affect disease phenotypes, and explore current and emerging therapies that target the gut microbiota as potential treatment for inflammatory diseases. PMID- 27195118 TI - Delayed adaptive immunity is related to higher MMR vaccine-induced antibody titers in children. AB - There are notable inter-individual variations in vaccine-specific antibody responses in vaccinated children. The aim of our study was to investigate whether early-life environmental factors and adaptive immune maturation prior and close to measles-mumps-rubella (MMR) immunization relate to magnitudes of vaccine specific antibody titers. In the FARMFLORA birth cohort, including both farming and non-farming families, children were immunized with the MMR vaccine at 18 months of age. MMR vaccine-induced antibody titers were measured in plasma samples obtained at 36 months of age. Infants' blood samples obtained at birth, 3 5 days and at 4 and 18 months of age were analyzed for T- and B-cell numbers, proportions of naive and memory T and B cells, and fractions of putative regulatory T cells. Multivariate factor analyses show that higher anti-MMR antibody titers were associated with a lower degree of adaptive immune maturation, that is, lower proportions of memory T cells and a lower capacity of mononuclear cells to produce cytokines, but with higher proportions of putative regulatory T cells. Further, children born by cesarean section (CS) had significantly higher anti-measles titers than vaginally-born children; and CS was found to be associated with delayed adaptive immunity. Also, girls presented with significantly higher anti-mumps and anti-rubella antibody levels than boys at 36 months of age. These results indicate that delayed adaptive immune maturation before and in close proximity to immunization seems to be advantageous for the ability of children to respond with higher anti-MMR antibody levels after vaccination. PMID- 27195119 TI - Gut macrophage phenotype is dependent on the tumor microenvironment in colorectal cancer. AB - In contrast to many cancers, a high infiltration of macrophages in colorectal cancer (CRC) has been associated with improved prognosis for patients. Cytokines and other stimuli from the tumor microenvironment affect monocyte to macrophage maturation and subsequent phenotype and function. Heterogeneous myeloid populations were identified using a novel flow cytometry panel in both tumor and paired non-tumor bowel (NTB) from CRC patients. The frequency of macrophage subsets with a gut-conditioned phenotype was lower in tumor compared with NTB. We used an in vitro system to show that two of the macrophage populations represented pro-inflammatory and anti-inflammatory phenotypes. Conditioned media that contained high levels of interleukin-6 promoted and maintained an anti inflammatory phenotype in vitro. This study demonstrates the plasticity and heterogeneity of macrophage subtypes in human CRC, and the feasibility of studying complex populations. Ex vivo experiments demonstrate that macrophage subsets are influenced by the tumor microenvironment. PMID- 27195121 TI - Emotion regulation difficulties in anorexia nervosa: associations with improvements in eating psychopathology. AB - BACKGROUND: Difficulties with emotion regulation have been established as a core deficit in anorexia nervosa (AN). However, limited research has evaluated whether weight gain is associated with improvements in emotion regulation difficulties in AN and whether improvements in emotion regulation are associated with reductions in eating disorder psychopathology. The aims of this study were threefold: 1) to examine the nature and extent of emotion regulation difficulties in AN; 2) to determine whether these difficulties improved during intensive treatment for the eating disorder; and 3) to study whether improvements in emotion regulation were associated with improvements in eating disorder psychopathology. METHOD: The participants were 108 patients who met DSM-IV-TR criteria for AN and were admitted to a specialized intensive treatment program. Self-report measures of eating disorder symptoms and difficulties with emotion regulation were administered at admission to and discharge from the program. RESULTS: Patients with the binge-purge subtype of AN reported greater difficulties with impulse control when upset and more limited access to emotion regulation strategies when experiencing negative emotions than those with the restricting subtype. Among those who completed treatment and became weight restored, improvements in emotion regulation difficulties were observed. Greater pre-to-post treatment improvements in emotional clarity and engagement in goal directed behaviours when upset were associated with greater reductions in eating disorder psychopathology during treatment. CONCLUSIONS: These findings add to growing evidence suggesting that eating disorder symptoms may be related to emotion regulation difficulties in AN and that integrating strategies to address emotion regulation deficits may be important to improving treatment outcome in AN. PMID- 27195122 TI - Factors impacting treatment and recovery in Anorexia Nervosa: qualitative findings from an online questionnaire. AB - BACKGROUND: Anorexia nervosa (AN) is characterised by restriction of energy intake, fear of gaining weight and severe disturbances in weight or shape. Recovery from AN is a complicated and often multifaceted experience that can take many years to achieve. Qualitative research has found that support, being understood, hope, desire for recovery, positive experiences in treatment, self efficacy, motivation and relationships are important in recovery from AN. The experience of treatment for patients with an eating disorder is an important aspect of recovery with the potential to enhance recovery or hinder it. The aim of the questionnaire was to better understand factors impacting the care experiences during treatment and or recovery from self-reported Anorexia Nervosa (AN). METHOD: An online questionnaire was developed and administered to past or current sufferers of Anorexia Nervosa, >=18 years of age. Participants were recruited through eating disorder organisations both in Australia and the United Kingdom. The questionnaire was a mixture of quantitative and qualitative questions. The quantitative data was analysed using descriptive statistics and the qualitative data was analysed using conventional content analysis (CCA). RESULTS: Of those who responded, most currently experienced self-reported AN. The quantitative results identified that most participants had trust and confidence in their health care provider and felt listened to and supported yet on the subject of the suitability of treatment this had varied opinions. Being understood, hope (life after AN) and self-acceptance were considered the top three important factors in the treatment and recovery from Anorexia Nervosa. The qualitative results revealed the factors hindering or benefiting treatment and recovery, and individuals' needs during the four phases of recovery. CONCLUSION: Factors were identified that could either hinder or benefit treatment and recovery and these included whether treatment supported the individual to cope with change, whether the individual found the treatment to be appropriate for their personal needs and whether treatment addressed underlying factors. Individuals' needs differed during the four phases of recovery. The findings of the study may help treatment providers address key factors involved in recovery at the right stage of treatment however by the nature of the qualitative methodology conclusions are putative and further definitive research is indicated. PMID- 27195120 TI - Sterile post-traumatic immunosuppression. AB - After major trauma, the human immune system initiates a series of inflammatory events at the injury site that is later followed by suppression of local inflammation favoring the repair and remodeling of the damaged tissues. This local immune response involves complex interactions between resident cells such as macrophages and dendritic cells, soluble mediators such as cytokines and chemokines, and recruited cells such as neutrophils, monocytes and mesenchymal stromal cells. If of sufficient magnitude, these initial immune responses nevertheless have systemic consequences resulting in a state called post traumatic immunosuppression (PTI). However, controversy exists regarding the exact immunological changes occurring in systemic compartments triggered by these local immune responses. PTI is one of the leading causes of post-surgical mortality and makes patients vulnerable to hospital-acquired infections, multiple organ failure and many other complications. In addition, hemorrhage, blood transfusion, immunesenescence and immunosuppressant drugs aggravate PTI. PTI has been intensively studied, but published results are frequently cloudy. The purpose of this review is to focus on the contributions made by different responsive modalities to immunosuppression following sterile trauma and to try to integrate these into an overall scheme of PTI. PMID- 27195124 TI - Mathematical modeling in municipal solid waste management: case study of Tehran. AB - BACKGROUND: Solid Waste Management (SWM) in metropolises with systematic methods and following environmental issues, is one of the most important subjects in the area of urban management. In this regard, it is regarded as a legal entity so that its activities are not overshadowed by other urban activities. In this paper, a linear mathematical programming model has been designed for integrated SWM. Using Lingo software and required data from Tehran, the proposed model has been applied for Tehran SWM system as a case study. RESULTS: To determine the optimal status of the available system for Tehran's Solid Waste Management System (SWMS), a novel linear programming model is applied. Tehran has 22 municipal regions with 11 transfer stations and 10 processing units. By running of the model, the transfer stations and processing units are decreased to 10 and 6 units, respectively. CONCLUSIONS: The proposed model is an alternative method for improvement the SWMS by decreasing the transfer stations and processing units. PMID- 27195123 TI - Neurobiological model of the persistence of anorexia nervosa. AB - Anorexia Nervosa (AN) is characterized by the maintenance of an undernourished, or starved, state. Persistent restrictive eating, or the recurrent intake of a diet that is inadequate to sustain a healthy weight, is the central behavior maintaining AN. To understand this disturbance, we need to understand the neural mechanisms that allow or promote the persistent choice of inadequate caloric intake. While a range of neural disturbances have been reported in AN, abnormalities in systems relevant to reward processing and the development of habit systems have been consistently described in both structural and functional neuroimaging studies. Most recently, brain and behavior have been directly examined by investigating the neural underpinnings of restrictive food choice. These recent data suggest that, among individuals with AN, dorsal frontostriatal circuits play a greater role in guiding decisions regarding what to eat than among healthy individuals. This line of research attempts to leverage advances in the field of cognitive neuroscience to further our understanding of persistent maladaptive choices of individuals with AN, in the hope that such advances will help in the development of novel treatments for this potentially fatal disorder. PMID- 27195125 TI - Pro-inflammatory effects of a litchi protein extract in murine RAW264.7 macrophages. AB - It has been observed that the consumption of litchi often causes symptoms characterized by itching or sore throat, gum swelling, oral cavity ulcers and even fever and inflammation, which significantly impair the quality of life of a large population. Using the RAW264.7 cell line, a step-by-step strategy was used to screen for the components in litchi fruits that elicited adverse reactions. The adverse reaction fractions were identified by mass spectrometry and analyzed using the SMART program, and a sequence alignment of the homologous proteins was performed. MTT tests were used to determine the cytotoxicity of a litchi protein extract in RAW264.7 macrophages, and real-time PCR was applied to analyze the expression of inflammatory genes in the RAW264.7 cells treated with lipopolysaccharide or the litchi protein extract. The results showed that the litchi water-soluble protein extract could increase the production of the pro inflammatory mediators IL-1beta, iNOS and COX-2, and the anti-inflammatory mediator HO-1 in the RAW264.7 cell line. The 14-3-3-like proteins GF14 lambda, GF14 omega and GF14 upsilon were likely the candidate proteins that caused the adverse effects. PMID- 27195126 TI - Neighbourhood socioeconomic context, individual socioeconomic position, and overweight in young children: a multilevel study in a large German city. AB - BACKGROUND: The context of the close neighbourhood environment in which children live has gained increasing attention in epidemiological research. This study aimed to investigate if contextual neighbourhood socioeconomic position (SEP) was independently associated with overweight in young children aged 5-7 years while simultaneously considering a wide range of individual socioeconomic determinants and known risk factors for overweight. METHODS: Objectively measured body mass index (BMI) data from 3499 children (53 % boys and 47 % girls) from three surveys between 2004 and 2007 clustered in 18 school enrolment zones in the city of Munich, Germany, were analysed with hierarchical logistic regression models. An index of neighbourhood SEP was calculated with principal component analysis using aggregated data. Individual socioeconomic data, maternal BMI, and birth weight were collected with parental questionnaires. We analysed how much of the between neighbourhood variance of overweight was attributable to individual factors and how much was explained by neighbourhood SEP. RESULTS: The prevalence of overweight, including obesity, was 14.1 %. In the final adjusted model low neighbourhood SEP was independently associated with overweight (odds ratio (OR) = 1.42, 95 % confidence interval (CI) = 1.00-2.00) compared to high neighbourhood SEP. On the individual level low parental education (OR = 1.99, 95 % CI = 1.49 2.65) or middle parental education (OR = 1.50, 95 % CI = 1.16-1.95) compared to high parental education and nationality of the child other than German (OR = 1.53, 95 % CI = 1.17-1.99) compared to German nationality were independently associated with overweight. CONCLUSIONS: Whereas individual determinants were the main drivers in explaining between neighbourhood variance, neighbourhood SEP additionally explained differences in overweight between neighbourhoods. Thus, considering neighbourhood context in intervention planning could result in more effective strategies compared to measures only focusing on individual determinants of overweight. PMID- 27195127 TI - An evaluation of entecavir treatment among nucleos(t)ide-naive Moroccan patients with chronic hepatitis B. AB - OBJECTIVE: To analyse the efficacy and safety of entecavir (ETV) treatment in nucleos(t)ide (NUC)-naive Moroccan patients with chronic hepatitis B. METHODS: We retrospectively analysed 41 NUT-naive Moroccan patients with chronic hepatitis B who received ETV 0,5 mg/day monotherapy for at least 3 months, of whom 3 were HBV envelope antigen (HbeAg) positive and 38 were HBeAg negative. The primary end point was the proportion of patients achieving virological response. Secondary end points included biochemical response (alanine transaminase (ALT) normalisation), serological response (HbeAg and HBV surface antigen (HBsAg) loss or seroconversion) and safety. RESULTS: The median follow-up duration was 74 weeks (48-144 weeks) and mean age was 43.8 years. Of 41 patients, 6 were primary non-responders and 2 achieved partial virological response at week 48, whereas 35 achieved undetectable hepatitis B virus (HBV) DNA at month 12. Viral suppression was maintained in 97.6% of patients after 3 years of ETV treatment. One patient experienced a virological breakthrough at month 12 of treatment. ALT normalisation occurred in 100% of the patients after 1 year of treatment. Only three patients in our study were HbeAg positive, of whom one has experienced seroconversion at month 12 of treatment. However, HBsAg loss or seroconversion was not achieved during the period of the study. No serious adverse event was reported. CONCLUSIONS: These preliminary results showed that ETV is a safe and potent inhibitor of HBV in NUC-naive Moroccan patients, but we need to observe more patients for a longer period of time, in order to assess the long-term effectiveness, safety, resistance profile and predictive factors for virological and serological response of ETV. PMID- 27195128 TI - Hyperbaric oxygen therapy stimulates colonic stem cells and induces mucosal healing in patients with refractory ulcerative colitis: a prospective case series. AB - BACKGROUND: Hyperbaric oxygen (HBO) is used as part of treatment in a variety of clinical conditions. Its use in the treatment of ulcerative colitis has been reported in few clinical reports. OBJECTIVE: We report the effect of HBO on refractory ulcerative colitis exploring one potential mechanism of action. DESIGN: A review of records of patients with refractory ulcerative colitis who received HBO was conducted. Clinical and histopathological scoring was utilised to evaluate the response to HBO therapy (HBOT). RESULTS: All patients manifested clinical improvement by the 40th cycle of HBOT. The median number of stool frequency dropped from seven motions/day (range=3-20) to 1/day (range=0.5-3), which was significant (z=-4.6, p<0.001). None of the patients manifested persistent blood passage after HBOT (z=-3.2, p=0.002). The severity index significantly improved after HBOT (z=-4.97, p<0.001). Histologically, a significant reduction of the scores of activity was recorded accompanied by a significant increase in the proliferating cell nuclear antigen labelling index of the CD44 cells of the colonic mucosa (p=0.001). CONCLUSIONS: HBOT is effective in the setting of refractory ulcerative colitis. The described protocol is necessary for successful treatment. HBOT stimulates colonic stem cells to promote healing. PMID- 27195129 TI - Initial US evaluation of second-generation capsule colonoscopy for detecting colon polyps. AB - OBJECTIVES: Capsule colonoscopy is an additional screening modality for colorectal cancer. Second-generation capsule colonoscopy (CC2) may have improved efficacy in the detection of colon adenomas as compared with prior devices. The purpose of this study was to evaluate the performance of CC2 in the detection of polyps in symptomatic and screening patients in the USA. DESIGN: Prospective, multicentre study. SETTING AND PARTICIPANTS: Two academic medical centres and two private practice facilities, evaluating patients with indications for colonoscopy. METHODS: Patients underwent capsule colonoscopy procedure using magnesium citrate as a boost, followed by colonoscopy on the same day. The main outcome measurement was accuracy of CC2 for the detection of colorectal polyps >=6 and >=10 mm as compared with conventional colonoscopy. RESULTS: 51 patients were enrolled, 50 of whom had CC2 and colonoscopy examinations and were included in the accuracy analysis. 30% and 14% of patients had polyps >=6 and >=10 mm, respectively. For lesions >=10 mm identified on conventional colonoscopy, CC2 sensitivity was 100% (95% CI 56.1% to 100%) with a specificity of 93.0% (79.9% to 98.2%). For polyps >=6 mm, the CC2 sensitivity was 93.3% (66.0% to 99.7%) and the specificity was 80.0% (62.5% to 90.9%). There was a 61% adequate cleansing rate with 64% of CC2 procedures being complete. CONCLUSIONS: In the initial US experience with CC2 there was adequate sensitivity for detecting patients with polyps >=6 mm in size. Magnesium citrate was inadequate as a boost agent. TRIAL REGISTRATION NUMBER: NCT01087528. PMID- 27195130 TI - Cost-effectiveness of adalimumab, infliximab or vedolizumab as first-line biological therapy in moderate-to-severe ulcerative colitis. AB - BACKGROUND: There are no head-to-head randomised controlled trials (RCTs) comparing the effectiveness of biologics in ulcerative colitis (UC). We aimed to assess the cost-effectiveness of adalimumab, infliximab and vedolizumab as first line agents to induce clinical remission and mucosal healing (MH) in UC. METHODS: We constructed a decision tree based on a payer's perspective in the USA to estimate the first year costs of adalimumab, infliximab or vedolizumab to achieve clinical remission and MH in patients with moderate-to-severe UC. Transition probabilities were derived from ACT, ULTRA and GEMINI RCT data. Costs were derived from Medicare reimbursement rates and wholesale drug prices. RESULTS: Assuming a biological-naive cohort, infliximab 5 mg/kg every 8 weeks was more cost-effective ($99 171 per MH achieved) than adalimumab 40 mg every other week ($316 378 per MH achieved) and vedolizumab every 8 weeks ($301 969 per MH achieved) at 1 year. Non-drug administration cost of infliximab exceeding $1974 per infusion would make adalimumab more cost-effective. First-line UC therapy with vedolizumab would be cost-effective if the drug acquisition price was <$2537 for each 300 mg administration during the 1-year time horizon. CONCLUSIONS: If non-drug costs of infliximab administration are not excessive (<$2000), infliximab is the most cost-effective first-line biologic for moderate-to-severe UC. Exceeding this threshold infusion-related cost would make adalimumab the more cost-effective therapy. Considering its drug costs in the USA, vedolizumab appears to be appropriately used as a second-line biologic after antitumour necrosis factor failure. PMID- 27195132 TI - Preface to the 3(rd) European Perspective in Thoracic Surgery special issue. PMID- 27195131 TI - Neuroretinal hypoxic signaling in a new preclinical murine model for proliferative diabetic retinopathy. AB - Diabetic retinopathy (DR) affects approximately one-third of diabetic patients and, if left untreated, progresses to proliferative DR (PDR) with associated vitreous hemorrhage, retinal detachment, iris neovascularization, glaucoma and irreversible blindness. In vitreous samples of human patients with PDR, we found elevated levels of hypoxia inducible factor 1 alpha (HIF1alpha). HIFs are transcription factors that promote hypoxia adaptation and have important functional roles in a wide range of ischemic and inflammatory diseases. To recreate the human PDR phenotype for a preclinical animal model, we generated a mouse with neuroretinal-specific loss of the von Hippel Lindau tumor suppressor protein, a protein that targets HIF1alpha for ubiquitination. We found that the neuroretinal cells in these mice overexpressed HIF1alpha and developed severe, irreversible ischemic retinopathy that has features of human PDR. Rapid progression of retinopathy in these mutant mice should facilitate the evaluation of therapeutic agents for ischemic and inflammatory blinding disorders. In addition, this model system can be used to manipulate the modulation of the hypoxia signaling pathways, for the treatment of non-ocular ischemic and inflammatory disorders. PMID- 27195133 TI - Vascular access for extracorporeal life support: tips and tricks. AB - In thoracic surgery, extracorporeal life support (ECLS) techniques are performed to (I) provide a short to mid term extracorporeal mechanical support; (II) realize the gas exchanges; and (III)-depending the configuration of the circuit substitute the failed heart function. The objective of this review is to describe the rational of the different ECLS techniques used in thoracic surgery and lung transplantation (LTx) with a specific attention to the vascular access. Venovenous extracorporeal membrane oxygenation (VV ECMO) is the most common ECLS technique used in thoracic surgery and represents the best strategy to support the lung function. VV ECMO needs peripheral vascular access. The selection between his double-site or single-site configuration should be decided according the level of O2 requirements, the nosological context, and the interest to perform an ECLS ambulatory strategy. Venoarterial (VA) ECMO uses peripheral and/or central cannulation sites. Central VA ECMO is mainly used in LTx instead a conventional cardiopulmonary bypass (CPB) to decrease the risk of hemorrhagic issues and the rate of primary graft dysfunction (PGD). Peripheral VA ECMO is traditionally realized in a femoro-femoral configuration. Femoro-femoral VA ECMO allows a cardiocirculatory support but does not provide an appropriate oxygenation of the brain and the heart. The isolated hypercapnic failure is currently supported by extracorporeal CO2 removal (ECCO2R) devices inserted in jugular or subclavian veins. The interest of the Novalung (Novalung GmbH, Hechingen, Germany) persists due to his central configuration indicated to bridge to LTx patients suffering from pulmonary hypertension. The increasing panel of ECLS technologies available in thoracic surgery is the results of a century of clinical practices, engineering progress, and improvements of physiological knowledges. The selection of the ECLS technique-and therefore the vascular access to implant the device-for a given nosological context trends to be defined according an evidence-based medicine. PMID- 27195134 TI - Non-intubated video-assisted thoracic surgery: where does evidence stand? AB - In recent years, non-intubated video-assisted thoracic surgery (NIVATS) strategies are gaining popularity worldwide. The main goal of this surgical practice is to achieve an overall improvement of patients' management and outcome thanks to the avoidance of side-effects related to general anesthesia (GA) and one-lung ventilation. The spectrum of expected benefits is multifaceted and includes reduced postoperative morbidity, faster discharge, decreased hospital costs and a globally reduced perturbation of patients' well-being status. We have conducted a literature search to evaluate the available evidence on this topic. Meta-analysis of collected results was also done where appropriate. Despite some fragmentation of data and potential biases, the available data suggest that NIVATS operations can reduce operative morbidity and hospital stay when compared to equipollent procedures performed under GA. Larger, well designed prospective studies are thus warranted to assess the effectiveness of NIVATS as far as to investigate comprehensively the various outcomes. Multi-institutional and multidisciplinary cooperation will be welcome to establish uniform study protocols and to help address the questions that are to be answered yet. PMID- 27195135 TI - Diaphragm pacing: the state of the art. AB - Diaphragm pacing (DP) is an orphan surgical procedure that may be proposed in strictly selected ventilator-dependent patients to get an active diaphragm contraction. The goal is to wean from mechanical ventilation (MV) and restore permanent efficient breathing. The two validated indications, despite the lack of randomised control trials, concern patients with high-level spinal cord injuries (SCI) and central hypoventilation syndromes (CHS). To date, two different techniques exist. The first, intrathoracic diaphragm pacing (IT-DP), based on a radiofrequency method, in which the electrodes are directly placed around the phrenic nerve. The second, intraperitoneal diaphragm pacing (IP-DP) uses intradiaphragmatic electrodes implanted through laparoscopy. In both techniques, the phrenic nerves must be intact and diaphragm reconditioning is always required after implantation. No perioperative mortality has been reported and ventilator weaning rate is about 72% to 96% in both techniques. Improvement of quality of life, by restoring a more physiological breathing, has been almost constant in patients that could be weaned. Failure or delay in recovery of effective diaphragm contractions could be due to irreversible amyotrophy or chest wall damage. Recent works have evaluated the interest of IP-DP in amyotrophic lateral sclerosis (ALS). After some short series were reported in the literature, the only multicentric randomized study including 74 ALS patients was prematurely stopped because of excessive mortality in paced patients. Then, another trial analysed the place of IP-DP in peripheral diaphragm dysfunction but, given the multiple biases, the published results cannot validate that indication. Reviewing all available literature as in our experience, shows that DP is an effective method to wean selected patients dependent on ventilator and improve their daily life. Other potential indications will have to be evaluated by randomised control trials. PMID- 27195137 TI - Surgery versus stereotactic ablative radiotherapy (SABR) for early-stage non small cell lung cancer: less is not more. AB - High level evidence from randomized studies comparing surgery to stereotactic ablative radiotherapy (SABR) is lacking and available retrospective cohort and case control studies are highly variable in how thoroughly they define and stage lung cancer, in how they determine operability, and in the offered surgical approaches to operable lung cancer (open vs. video-assisted). This makes it difficult to compare best radiotherapy and best surgery approaches to treatment and to be confident in conclusions of equipoise between the two modalities. What has become clear from the controversy surrounding surgery versus SABR for early stage lung cancer is the desire to optimize treatment efficacy while minimizing invasiveness and morbidity. This review highlights the ongoing debate in light of these goals. PMID- 27195136 TI - European perspective in Thoracic surgery-eso-coloplasty: when and how? AB - Colon interposition has been used since the beginning of the 20(th) century as a substitute for esophageal replacement. Colon interposition is mainly chosen as a second line treatment when the stomach cannot be used, when the stomach has to be resected for oncological or technical reasons, or when the stomach is deliberately kept intact for benign diseases in young patients with long-life expectancy. During the surgery the vascularization of the colon must be carefully assessed, as well as the type of the graft (right or left colon), the length of the graft, the surgical approach and the route of the reconstruction. Early complications such as graft necrosis or anastomotic leaks, and late complications such as redundancy depend on the quality of the initial surgery. Despite a complex and time-consuming procedure requiring at least three or four digestive anastomoses, reported long term functional outcomes of colon interposition are good, with an acceptable operative risk. Thus, in very selected indications, colon interposition could be seen as a valuable alternative for esophageal replacement when stomach cannot be considered. This review aims at briefly defining "when" and "how" to perform a coloplasty through demonstrative videos. PMID- 27195138 TI - Minimally invasive (robotic assisted thoracic surgery and video-assisted thoracic surgery) lobectomy for the treatment of locally advanced non-small cell lung cancer. AB - BACKGROUND: Insufficient data exist on the results of minimally invasive surgery (MIS) for locally advanced non-small cell lung cancer (NSCLC) traditionally approached by thoracotomy. The use of telerobotic surgical systems may allow for greater utilization of MIS approaches to locally advanced disease. We will review the existing literature on MIS for locally advanced disease and briefly report on the results of a recent study conducted at our institution. METHODS: We performed a retrospective review of a prospective single institution database to identify patients with clinical stage II and IIIA NSCLC who underwent lobectomy following induction chemotherapy. The patients were classified into two groups (MIS and thoracotomy) and were compared for differences in outcomes and survival. RESULTS: From January 2002 to December 2013, 428 patients {397 thoracotomy, 31 MIS [17 robotic and 14 video-assisted thoracic surgery (VATS)]} underwent induction chemotherapy followed by lobectomy. The conversion rate in the MIS group was 26% (8/31) The R0 resection rate was similar between the groups (97% for MIS vs. 94% for thoracotomy; P=0.71), as was postoperative morbidity (32% for MIS vs. 33% for thoracotomy; P=0.99). The median length of hospital stay was shorter in the MIS group (4 vs. 5 days; P<0.001). The 3-year overall survival (OS) was 48.3% in the MIS group and 56.6% in the thoracotomy group (P=0.84); the corresponding 3-year DFS were 49.0% and 42.1% (P=0.19). CONCLUSIONS: In appropriately selected patients with NSCLC, MIS approaches to lobectomy following induction therapy are feasible and associated with similar disease-free and OS to those following thoracotomy. PMID- 27195139 TI - Opportunities and challenges for thoracic surgery collaborations in China: a commentary. AB - Through a unique combination of factors-including a huge population, rapid social development, and concentration of resources in its mega-cities-China is witnessing phenomenal developments in the field of thoracic surgery. Ultra-high volume centers are emerging that provide fantastic new opportunities for surgical training and clinical research to surgeons in China and partners from other countries. However, there are also particular shortcomings that are limiting clinical and academic developments. To realize the potential and reap the rewards, the challenges posed by these limitations must be overcome. Thoracic surgeons from Europe may be particularly well-placed to achieve this through multi-dimensional exchanges with their Chinese counterparts. PMID- 27195140 TI - VATS lobectomy program: the trainee perspective. AB - Due to its intrinsic characteristics, video assisted thoracic surgery (VATS) lobectomy is currently the recommended surgical approach for early stage lung cancer treatment. The importance of increasing the number of surgeons capable of performing VATS lobectomies is implicit and of utmost importance. In fact, the need of performing independently and routinely VATS lobectomies for early stage lung cancer will soon be a prerequisite to the new generation of thoracic surgeons. The feeling that VATS lobectomy teaching should be part of their training is strongly felt among trainees but, at the moment, a formal, uniform and certified process of learning VATS lobectomy is not available in all training centres. Perhaps, through the supervision, support and aid from national and European Thoracic Surgery Societies, programs of integration of recognized, standardized and certified teaching of VATS lobectomy could be planned and undertaken by the training centres, both at national as well as European level. PMID- 27195141 TI - Comparison of Subjective Wellbeing and Positive Future Expectations in Between Working and Nonworking Adolescents in Turkey. AB - BACKGROUND: Wellbeing is one's evaluation and judgment of one's life. It consists of 3 dimensions: positive affectivity, negative affectivity, and life satisfaction. OBJECTIVES: This study aimed to compare the subjective wellbeing and positive future expectations between working and nonworking adolescents. PATIENTS AND METHODS: The study was designed as descriptive and comparative. The study sample consisted of 420 working and 482 nonworking adolescents (n = 902) aged 15 - 20 years, who were randomly recruited from two occupational education centers in Istanbul, Turkey and two high schools (formal educations) in the same district. RESULTS: Adolescent subjective wellbeing scale (ASWS) total mean (SD) scores for working adolescents and nonworking adolescents were 48.76 (9.50) and 49.72 (8.01), respectively. In addition, positive future expectations scale (PFES) total mean (SD) scores for working adolescents and nonworking adolescents were 18.71 (4.50) and 19.06 (3.49), respectively. In this study, no significant difference was found between the general wellbeing (scale total median score) scores of the working and nonworking adolescent groups (Z = 1.01, P = 0.315). However, significant differences were found in the family relations satisfaction (Z = 3.23, P = 0.002) and relations with significant others (Z = 2.85, P = 0.004) subscales of the ASWS. CONCLUSIONS: A positive relationship was found between adolescent subjective wellbeing and positive future expectations. It was found that nonworking adolescents scored higher on the dimensions of "family relations" and "relations with significant others" of subjective wellbeing compared to those dimensions in working adolescents. PMID- 27195142 TI - Long-Term Exposure of Lead Acetate on Rabbit Renal Tissue. AB - BACKGROUND: Lead has been widely used in different industries for ages. It is one of the heavy metals, highly poisonous even at low doses, and has biochemical, physiological and behavioral side effects on human and animals. It has been shown that lead has toxic effects on different tissues such as neural and genitourinary tissues, cardiovascular systems and blood. Therefore, high attention has been paid to its environmental pollutions. OBJECTIVES: Although many histological and biochemical studies have reported about the effects of lead on the renal tissue, there are a few studies about the ultrastructure and morphometric effects of lead on the kidney. Hence, the aim of this study was the evaluation of morphology and morphometrics of rabbit renal urinary barrier ultrastructure following long-term exposure to lead acetate. MATERIALS AND METHODS: In this experimental study, 20 male New Zealand rabbits were divided into control and test groups (10 in each). The test group was injected intraperitoneally with chronic dose (8.5 mg/kg of body weight) of lead acetate and for the control group the same volume of normal saline was used, every other day for 10 weeks. After anesthetizing, the biopsies of renal tissues were taken for light and electron microscopic morphometric and morphologic analyses. RESULTS: Long-term exposure to lead acetate caused histopathology effects including dilatation, congestion, nuclei heterochromatic effects, increase in diameter of renal tubules and urinary barrier thickness in rabbit renal tissue. CONCLUSIONS: Quantitative and qualitative results of long term lead acetate exposure showed many histopathology side-effects, especially in the urinary barrier. PMID- 27195144 TI - Idiopathic Systemic Capillary Leak Syndrome: A Case Report. AB - INTRODUCTION: Idiopathic systemic capillary leak syndrome (ISCLS) is rarely seen, and presents with recurrent episodes of hypotension, shock, hemoconcentration, and hypoproteinemia. The main pathology is the dysfunction of the vascular endothelium, and it is characterized by an increase of capillary permeability that is accompanied by the loss of intravascular fluid and protein. CASE PRESENTATION: We present a 58-year-old female who presented with peripheral edema, leg pain, and syncope at the emergency department. Interestingly demyemilising neuropathy, which is a rare finding, ensued on day 4. She is still being treated using intravenous immunoglobulin therapy. CONCLUSIONS: The early signs and symptoms of ISCLS may be subtle; therefore the diagnosis can easily be missed and prompt treatment of the syndrome may be postponed. Thus, the clinician must consider ISCLS in differential diagnosis in cases of hypotension, hemoconcentration, and hypoalbuminemia. PMID- 27195143 TI - Distribution of Genes Encoding Resistance to Macrolides Among Staphylococci Isolated From the Nasal Cavity of Hospital Employees in Khorramabad, Iran. AB - BACKGROUND: Epidemiological data on antibiotic susceptibility of Staphylococcus strains isolated from nasal carriers in each region can be helpful to select appropriate drugs to eradicate carriage states, control nosocomial infections and also treat patients. OBJECTIVES: The current study aimed to investigate the antibiotic resistance profile and the molecular prevalence of the ermA, ermB, ermC and msrA genes among Staphylococcus strains isolated from the anterior nares of hospital employees. PATIENTS AND METHODS: In this cross-sectional study, a total of 100 Staphylococcus isolates, 51 Staphylococcus aureus, 49 coagulase negative staphylococci (CoNS) were isolated from the anterior nares of hospital employees in Khorramabad, Iran. Susceptibility pattern to macrolide antibiotics were determined using the disk diffusion method. The polymerase chain reaction (PCR) assay was applied to determine the major erythromycin-resistant genes (ermA, ermB, ermC and msrA). RESULTS: Fifty-three (53%) isolates were simultaneously resistant to erythromycin, azithromycin and clarithromycin (cross resistance); while 8 (8%) isolates had variable macrolide susceptibility pattern. Among the S. aureus isolates, the difference in prevalence of resistance to erythromycin between males and females was significant (P = 0.011). The frequency of ermA, ermB, ermC, and msrA genes were 3%, 5%, 33% and 20%, respectively. It was also found that out of 53 isolates resistant to erythromycin, 44 (83%) isolates (eight S. aureus and thirty-six CoNS strains) carried at least one of the four tested genes. Eight (8%) isolates had intermediate phenotype to erythromycin, in which 4 (50%) isolates carried ermB or ermC genes. In addition, out of 39 erythromycin-susceptible isolates, 3 (7.7%) isolates were positive for ermB or ermC genes. CONCLUSIONS: No entire association was found between genotype and phenotype methods to detect macrolides-resistant isolates. In addition, distribution of genetically erythromycin-resistant isolates is geographically different among staphylococci. It is recommend removing S. aureus from nasal carriers by proved approaches such as local or systemic administration of effective antibiotics or bacterial interference. PMID- 27195145 TI - Comparing Gabapentin and Celecoxib in Pain Management and Complications After Laminectomy: A Randomized Double-Blind Clinical Trial. AB - BACKGROUND: Complications and postoperative pain are major care problems that can affect the quality of health care plan. OBJECTIVES: According to the use of multimodal therapy the current study aimed to compare the efficacy of gabapentin and celecoxib in pain management and complications after laminectomy at Ilam University of Medical Sciences, Ilam, Iran, in 2015. PATIENTS AND METHODS: In this randomized double-blind clinical trial, 114 patients scheduled for elective laminectomy with simple random sampling design received gabapentin (n = 38, 900 mg/day), celecoxib (n = 38, 600 mg/day) and placebo (n = 38, capsule contain starch). Visual analog scale (VAS) was used to determine the intensity of pain. Complications after surgery, anxiety scores before surgery and patient's satisfaction 24 hours after the surgery were recorded. RESULTS: The mean pain intensity in the gabapentin group was lower compared to those of the placebo and celecoxib groups respectively at different time durations (P < 0.001). The means of morphine consumption were 11.9 mg, 22.8 mg and 30.1 mg in the gabapentin, celecoxib and placebo groups, respectively (P < 0.001). The prevalence of shivering, nausea, vomiting and pruritus were 10.5%, 12.8%, 10.3% and 18.4% in the gabapentin group vs 31.5%, 29.8%, 32.4% and 28.9% in the celecoxib group and 42.1%, 44.7%, 39.5% and 44.7% in the placebo group (P < 0.001). The mean anxiety score in the gabapentin group was 2.4 vs those of the celecoxib group 3 and placebo group 3.6 (P < 0.001). The frequencies of drowsiness were 42.1%, 13.2% and 5.3% in the gabapentin, celecoxib and placebo groups, respectively (P < 0.001). In the gabapentin group, patient satisfaction was significantly higher compared to those of the placebo and celecoxib groups (P < 0.05). CONCLUSIONS: According to the effect of gabapentin on pain management, complications after laminectomy and increased patients satisfaction, it can be regarded as an alter native in multimodal analgesia. PMID- 27195146 TI - Intrastromal Injection of China Painting Ink in Corneas of Male Rabbits: Clinical and Histological Study. AB - Background. Many patients with corneal opacity or complicated cataract in blind eye ask for cosmoses. In this study we tried to investigate the staining of corneas of male rabbits by Rotring China painting ink and to study the histological changes. Method. 10 eyes of 10 male Baladi Egyptian rabbits were injected (0.1 mL) intrastromally in the cornea by the use of China painting ink (Rotring Tinta China) through insulin syringe (27-gauge needle) by single injection; clinical follow-up is for 6 months and lastly the rabbits were scarified and the stained eyes were enucleated for histological analysis. Results. Clinically the stain was stable in color and distribution in corneas with no major complications. Histological results of the stained rabbit corneas showed blackish pigmentation in the corneal stroma without any inflammatory cellular infiltration. Some fibroblast cells had pigment granules in their cytoplasm in the adjacent layers. Conclusion. Corneal staining by China painting ink is effective and safe in staining of male rabbits cornea; however further study in human corneas with longer follow-up period is advisable. PMID- 27195147 TI - Transfusion Thresholds, Quality of Life, and Current Approaches in Myelodysplastic Syndromes. AB - Hemoglobin thresholds and triggers for blood transfusions have changed over the years moving from a higher to a lower level. This review article summarizes the current evidence of transfusion thresholds in the hospitalized as well as in the outpatient setting and particularly in myelodysplasia. Fatigue is the main reported symptom in this group of patients and current clinical trials are looking for a more liberal approach of red cell transfusion and the effect on quality of life as opposed to the restrictive strategy used in the critical care setting. Practical considerations, the cost effectiveness of this strategy in addition to the possible complications, and the use of quality of life questionnaires have also been reviewed. PMID- 27195148 TI - Neutropenic Sepsis in the ICU: Outcome Predictors in a Two-Phase Model and Microbiology Findings. AB - Objective. Patients with neutropenic sepsis have a poor prognosis. We aimed to identify outcome predictors and generate hypotheses how the care for these patients may be improved. Methods. All 12.352 patients admitted between 2006 and 2011 to the medical ICUs of our tertiary university center were screened for neutropenia; out of 558 patients identified, 102 fulfilled the inclusion criteria and were analyzed. Severity markers and outcome predictors were assessed. Results. The overall ICU mortality was 54.9%. The severity of sepsis and the number of organ failures predicted survival of the primary septic episode (APACHE II 22.8 and 29.0; SOFA 7.3 and 10.1, resp.). In the recovery phase, persistent organ damage and higher persistent C-reactive protein levels were associated with a poor outcome. Blood transfusions and CMV infection correlated with an unfavorable prognosis. Ineffective initial antibiotic therapy, fungal infections, and detection of multiresistant bacteria displayed a particularly poor outcome. Infections with coagulase-negative staphylococci and enterococci were associated with a significantly higher mortality and a high degree of systemic inflammation. Conclusion. Patients with persistent organ dysfunction show an increased mortality in the further course of their ICU stay. Early antimicrobial treatment of Gram-positive cocci may improve the outcome of these patients. PMID- 27195149 TI - Two-Year Follow-Up Analysis of Telaprevir-Based Antiviral Triple Therapy for HCV Recurrence in Genotype 1 Infected Liver Graft Recipients as a First Step towards Modern HCV Therapy. AB - Objective. The introduction of protease inhibitors telaprevir and boceprevir in 2011 had extended the antiviral treatment options especially in genotype 1 infected hepatitis C relapsers and nonresponders to interferon/ribavirin therapy. The aim of this study was to analyze the long-term treatment efficiency of telaprevir-based triple therapy for patients with hepatitis C reinfection after orthotopic liver transplantation. Patients and Methods. We included 12 patients with histologically confirmed graft fibrosis due to hepatitis C reinfection. The treatment duration was scheduled as 12 weeks of telaprevir-based antiviral triple therapy followed by 36 weeks of dual therapy with pegylated interferon/ribavirin. The patients were followed up for two years after the end of triple therapy. Results. Of the 12 patients, 6 (50%) completed the full 48 weeks of antiviral treatment. An end of treatment response and a sustained virological response 52 weeks after the end of the antiviral treatment course were achieved in 8/12 (67%) and 7/12 (58%) patients, respectively. Conclusion. Telaprevir-based triple therapy was shown to be a long-term effective but complex treatment option for individual patients with hepatitis C graft. With the recent improvements in hepatitis C therapy options telaprevir may not be recommended as a standard therapy for this indication anymore. PMID- 27195151 TI - The Activity of Surface Electromyographic Signal of Selected Muscles during Classic Rehabilitation Exercise. AB - Objectives. Prone bridge, unilateral bridge, supine bridge, and bird-dog are classic rehabilitation exercises, which have been advocated as effective ways to improve core stability among healthy individuals and patients with low back pain. The aim of this study was to investigate the activity of seven selected muscles during rehabilitation exercises through the signal of surface electromyographic. Approaches. We measured the surface electromyographic signals of four lower limb muscles, two abdominal muscles, and one back muscle during rehabilitation exercises of 30 healthy students and then analyzed its activity level using the median frequency method. Results. Different levels of muscle activity during the four rehabilitation exercises were observed. The prone bridge and unilateral bridge caused the greatest muscle fatigue; however, the supine bridge generated the lowest muscle activity. There was no significant difference (P > 0.05) between left and right body side muscles in the median frequency slope during the four rehabilitation exercises of seven muscles. Conclusions. The prone bridge can affect the low back and lower limb muscles of most people. The unilateral bridge was found to stimulate muscles much more active than the supine bridge. The bird dog does not cause much fatigue to muscles but can make most selected muscles active. PMID- 27195152 TI - Physical and Psychosocial Functions of Adults with Lower Limb Congenital Deficiencies and Amputations in Childhood. AB - Objectives. (1) To describe the epidemiological and medical features of a sample with LLA and LLD in childhood and (2) to explore their relationship with subsequent physical and psychosocial functions in adulthood. Methods. Cross sectional survey. Demographics, medical data, Locomotor Capabilities Index (LCI), and Discomfort-Engagement in Everyday Activities Involving Revealing the Body Scale (D-EEARB) were collected from thirty-two adults who suffered from LLA in childhood or LLD. Results. Most of the sample (53.1% males) was working (84.4%), living independently (75%), and single (75%). Mean age was 33.16 (SD = 7.64, range 18-50). Leading causes for LLA were traumatic (40.6%) and oncologic (25%). LLD was present in 6 cases (18.8%). LCI scores revealed a high performance among males (t 17,464 = 2.976, p = .008). D-EEARB scores showed that 56.25% stated feeling "quite" or "totally comfortable" in situations which involved revealing their body, but 43.75% stated the contrary ("uncomfortable" or "very uncomfortable"). LLD and traumatic LLA show higher scores in D-EEARB than vascular and oncological LLA (chi (2) = 7.744, df = 3, p = .05). Conclusions. Adults suffering from LLDs and LLAs during childhood seem to perform well once they are adults. However, 43.75% of patients express considerable discomfort in situations that involve revealing the body. PMID- 27195150 TI - A Low-Protein Diet Enhances Angiotensin II Production in the Lung of Pregnant Rats but not Nonpregnant Rats. AB - Pulmonary angiotensin II production is enhanced in pregnant rats fed a low protein (LP) diet. Here we assessed if LP diet induces elevations in angiotensin II production in nonpregnant rats and whether Ace expression and ACE activity in lungs are increased. Nonpregnant rats were fed a normal (CT) or LP diet for 8, 12, or 17 days and timed pregnant rats fed for 17 days from Day 3 of pregnancy. Plasma angiotensin II, expressions of Ace and Ace2, and activities of these proteins in lungs, kidneys, and plasma were measured. These parameters were compared among nonpregnant rats or between nonpregnant and pregnant rats fed different diets. Major findings are as follows: (1) plasma angiotensin II levels were slightly higher in the LP than CT group on Days 8 and 12 in nonpregnant rats; (2) expression of Ace and Ace2 and abundance and activities of ACE and ACE2 in lungs, kidneys, and plasma of nonpregnant rats were unchanged by LP diet except for minor changes; (3) the abundance and activities of ACE in lungs of pregnant rats fed LP diet were greater than nonpregnant rats, while those of ACE2 were decreased. These results indicate that LP diet-induced increase in pulmonary angiotensin II production depends on pregnancy. PMID- 27195154 TI - A Case of Arterial and Venous Tear during Single Lead Extraction. AB - Transcutaneous lead extraction can be associated with significant morbidity and mortality. The risk of causing concomitant arterial and venous injury is rare. We report a case of marginal artery rupture with coronary sinus rupture after a CS lead extraction. A 71-year-old male was admitted for extraction of a 6-year-old implantable cardioverter-defibrillator lead due to fracture from insulation break. During the lead extraction, blood pressure fell precipitously and echocardiographic findings were consistent with pericardial effusion. After unsuccessful pericardiocentesis, open chest sternotomy and evacuation of hematoma was performed. Subsequent surgical repair of several injuries was completed including the distal coronary sinus, a large degloving injury of posterior portion of the heart, and first obtuse marginal branch bleed. This case demonstrates that when performing transcutaneous lead extraction (TLE) with laser sheath, a degloving injury can cause arterial rupture with concomitant coronary sinus injury. A multidisciplinary team-based approach can ensure patient safety. Learning Objective. Implantable cardioverter-defibrillator leads will falter over time. With the advancement of new technology for extraction more frequent and serious complications will occur. Active fixation CS leads present unique challenges. In the presence of hemodynamic changes during extraction the occurrence of both an arterial and venous injury must be considered. PMID- 27195155 TI - Seven-Year Follow-Up of Peutz-Jeghers Syndrome. AB - One of the clinicopathological criteria for diagnosing Peutz-Jeghers syndrome (PJS) is mucocutaneous pigmentation. We present a 57-year-old Iranian female patient with diffuse pigmentation in buccal and labial mucosa. The first colonoscopy revealed one 0.5 cm rectal polyp. However surveillance colonoscopies over a 7-year polyp showed over 100 colorectal polyps. PMID- 27195156 TI - Immediate Esthetic Rehabilitation of Periodontally Compromised Anterior Tooth Using Natural Tooth as Pontic. AB - For patients who require removal of anterior teeth and their replacement various treatment modalities are available. With advancement in technology and availability of glass/polyethylene fibres, use of natural tooth as pontic with fibre reinforced composite restorations offers the promising results. The present case report describes management of periodontally compromised mandibular anterior tooth using natural tooth pontic with fibre reinforcement. A 1-year follow-up showed that the bridge was intact with good esthetics and no problem was reported. PMID- 27195157 TI - Gigantomastia and Macroprolactinemia Responding to Cabergoline Treatment: A Case Report and Minireview of the Literature. AB - Background. Macroprolactinemia is defined as predominance of high molecular weight prolactin forms in the circulation. Although macroprolactin is considered as a biologically inactive molecule, some authorities suggest treatment in symptomatic cases. Gigantomastia is defined as excess breast tissue and most cases in the literature were treated by surgical intervention. Case. A 44-year old woman was admitted to our clinic with gigantomastia and galactorrhea. The patient had a demand for surgical therapy. In laboratory examination, she had hyperprolactinemia and macroprolactinemia. Pituitary imaging revealed 6 mm microadenoma in right side of the hypophysis. Since she was symptomatic, cabergolin treatment was started. Macroprolactin became negative, breast circumference decreased significantly, and galactorrhea resolved after treatment. Conclusion. Gigantomastia might be the presenting symptom in patients with macroprolactinemia. In these patients medical treatment with cabergoline may be used initially as an alternative to surgical approach. PMID- 27195158 TI - Herpes Simplex Virus-2 Esophagitis in a Young Immunocompetent Adult. AB - Herpes simplex esophagitis (HSE) is commonly identified in immunosuppressed patients. It is rare among immunocompetent patients and almost all of the reported cases are due to HSV-1 infection. HSV-2 esophagitis is extremely rare. We report the case of a young immunocompetent male who presented with dysphagia, odynophagia, and epigastric pain. Endoscopy showed multitudes of white nummular lesions in the distal esophagus initially suspected to be candida esophagitis. However, classic histopathological findings of multinucleated giant cells with eosinophilic intranuclear inclusions and positive HSV-2 IgM confirmed the diagnosis of HSV-2 esophagitis. The patient rapidly responded to acyclovir treatment. Although HSV-2 is predominantly associated with genital herpes, it can cause infections in other parts of the body previously attributed to only HSV-1 infection. PMID- 27195159 TI - Whole Exome Sequencing Leading to the Diagnosis of Dysferlinopathy with a Novel Missense Mutation (c.959G>C). AB - Dysferlinopathy is an uncommon, progressive muscular dystrophy that has a wide phenotypic variability and primarily supportive management (Nguyen et al., 2007; Narayanaswami et al., 2014). Amyloid myopathy is a distinct, rare disorder that can present similarly to inflammatory myopathies and requires a high clinical suspicion for early intervention to prolong survival. Amyloid myopathy is typically associated with other systemic manifestations of amyloidosis, but rare cases of isolated amyloid myopathy have been described (Mandl et al., 2000; Hull et al., 2001). Positive Congo red stains on tissue biopsy remain the gold standard for diagnosis (Spuler et al., 1998; Karacostas et al., 2005). A high clinical suspicion and meticulous diagnostic workup that includes novel techniques are necessary for identifying these rare disorders. We report a middle aged man with progressive leg muscle weakness who was initially treated as having amyloid myopathy but was later diagnosed as having dysferlinopathy by Whole Exome Sequencing (WES) analysis. We also report a novel missense mutation (c.959G>C) to help correlate in any patient with presumed dysferlinopathy and to add to the already known genotype of this disorder. PMID- 27195160 TI - Endoport-Assisted Microsurgical Treatment of a Ruptured Periventricular Aneurysm. AB - Background and Importance. Ruptured periventricular aneurysms in patients with moyamoya disease represent challenging pathologies. The most common methods of treatment include endovascular embolization and microsurgical clipping. However, rare cases arise in which the location and anatomy of the aneurysm make these treatment modalities particularly challenging. Clinical Presentation. We report a case of a 34-year-old female with moyamoya disease who presented with intraventricular hemorrhage. CT angiography and digital subtraction angiography revealed an aneurysm located in the wall of the atrium of the right lateral ventricle. Distal endovascular access was not possible, and embolization risked the sacrifice of arteries supplying critical brain parenchyma. Using the BrainPath endoport system, the aneurysm was able to be accessed. Since the fusiform architecture of the aneurysm prevented clip placement, the aneurysm was ligated with electrocautery. Conclusion. We demonstrate the feasibility of endoport-assisted approach for minimally invasive access and treatment of uncommon, distally located aneurysms. PMID- 27195153 TI - Modulation of Synaptic Plasticity by Glutamatergic Gliotransmission: A Modeling Study. AB - Glutamatergic gliotransmission, that is, the release of glutamate from perisynaptic astrocyte processes in an activity-dependent manner, has emerged as a potentially crucial signaling pathway for regulation of synaptic plasticity, yet its modes of expression and function in vivo remain unclear. Here, we focus on two experimentally well-identified gliotransmitter pathways, (i) modulations of synaptic release and (ii) postsynaptic slow inward currents mediated by glutamate released from astrocytes, and investigate their possible functional relevance on synaptic plasticity in a biophysical model of an astrocyte-regulated synapse. Our model predicts that both pathways could profoundly affect both short and long-term plasticity. In particular, activity-dependent glutamate release from astrocytes could dramatically change spike-timing-dependent plasticity, turning potentiation into depression (and vice versa) for the same induction protocol. PMID- 27195161 TI - Durable Clinical Benefit of Pertuzumab in a Young Patient with BRCA2 Mutation and HER2-Overexpressing Breast Cancer Involving the Brain. AB - Patients with HER2-positive breast cancer and brain metastases have limited treatment options, and, as a result of their poor performance status and worse prognosis, they are underrepresented in clinical trials. Not surprisingly, these patients may not be fit enough to receive any active treatment and are offered supportive therapy. BRCA2 mutations are reported to be rarely associated with HER2-overexpressing advanced breast cancer and even more rarely with brain metastases at diagnosis. We report on a BRCA2-positive breast cancer patient with metastatic disease in multiple sites, including the brain, and poor performance status who exhibited an extraordinary clinical and imaging response to the novel anti-HER2 therapy pertuzumab after multiple lines of therapy including anti-HER2 targeting. To our knowledge, the clinicopathologic and therapeutic characteristics of this patient point to a unique case and an urgent need for further investigation of pertuzumab in patients with brain metastases. PMID- 27195162 TI - A Case of Hyperammonemia Associated with High Dihydropyrimidine Dehydrogenase Activity. AB - Over the past decades, 5-Fluorouracil (5-FU) has been widely used to treat several types of carcinoma, including esophageal squamous cell carcinoma. In addition to its common side effects, including diarrhea, mucositis, neutropenia, and anemia, 5-FU treatment has also been reported to cause hyperammonemia. However, the exact mechanism responsible for 5-FU-induced hyperammonemia remains unknown. We encountered an esophageal carcinoma patient who developed hyperammonemia when receiving 5-FU-containing chemotherapy but did not exhibit any of the other common adverse effects of 5-FU treatment. At the onset of hyperammonemia, laboratory tests revealed high dihydropyrimidine dehydrogenase (DPD) activity and rapid 5-FU clearance. Our findings suggested that 5-FU hypermetabolism may be one of the key mechanisms responsible for hyperammonemia during 5-FU treatment. PMID- 27195163 TI - Unilateral Optic Neuritis: A Rare Complication after Measles-Mumps-Rubella Vaccination in a 30-Year-Old Woman. AB - Purpose. To report a case of unilateral optic neuritis following Measles-Mumps Rubella (MMR) vaccination. Methods. A 30-year-old female developed unilateral optic neuritis five days after a Measles-Mumps-Rubella (MMR) booster vaccination. The patient displayed unilateral involvement, with severe visual loss. However, visual acuity improved significantly after four days of intravenous steroid therapy with 500 mg/day of methylprednisolone. Conclusions. Optic neuritis is one of the rare complications associated with the mumps, measles, and rubella vaccine. It may be a toxic reaction to the nonviral component of the vaccine, but the exact etiology is unknown. Postvaccination neuritis is generally bilateral and usually affects children. In adults, unilateral optic neuritis is usually correlated with multiple sclerosis (MS). PMID- 27195164 TI - Successful Treatment of Bacillus cereus Bacteremia in a Patient with Propionic Acidemia. AB - Bacillus cereus can cause serious, life-threatening, systemic infections in immunocompromised patients. The ability of microorganism to form biofilm on biomedical devices can be responsible for catheter-related bloodstream infections. Other manifestations of severe disease are meningitis, endocarditis, osteomyelitis, and surgical and traumatic wound infections. The most common feature in true bacteremia caused by Bacillus is the presence of an intravascular catheter. Herein, we report a case of catheter-related bacteremia caused by B. cereus in a patient with propionic acidemia. PMID- 27195165 TI - Onychomycosis due to Candida parapsilosis in a Child with Ventricular Septal Defect: An Unusual Predisposition. AB - Candida parapsilosis is emerging as a potential pathogen for onychomycosis. A 4 year-old male child with perimembranous ventricular septal defect (VSD) was admitted with features of cystitis and was treated with broad spectrum antibiotics. Two weeks later, he developed yellowish discoloration of nails of both hands. The sloughed out nail, on microscopy, showed numerous yeast forms that were identified as Candida parapsilosis by both phenotypic and genotypic methods. Antifungal sensitivity testing of the isolate was performed by microbroth dilution method in accordance with CLSI guidelines. Patient was successfully treated with topical amphotericin B and oral fluconazole. Thus, one should have a high index of suspicion of C. parapsilosis onychomycosis, especially when the patient is in the paediatric age group, presenting with unusual predisposing condition like congenital heart disease, and is on broad spectrum antibiotics. PMID- 27195166 TI - Reticulated, Hyperchromic Rash in a Striated Pattern Mimicking Atopic Dermatitis and Fungal Infection in a 2-Month-Old Female: A Case of Incontinentia Pigmenti. AB - We present a 12-month-old Hispanic female with a reticulated, hyperchromic rash in a striated pattern appearing on upper and lower extremities and trunk and back since the age of 6 weeks. Over the next 10 months, the rash persisted. The rash did not respond to treatment with antifungals and steroids. During her 6-month wellness visit, the patient was diagnosed with incontinentia pigmenti (IP), a rare X-linked dominant disorder, fatal to male fetuses in utero. IP can lead to serious neurological and ophthalmologic consequences. Early diagnosis by primary care physicians and parental education about the condition are essential for prevention of retinal detachment, developmental delay, and dental abnormalities. PMID- 27195167 TI - Robotic Compartment-Based Radical Surgery in Early-Stage Cervical Cancer. AB - A radical hysterectomy with pelvic lymphadenectomy is the recommended treatment option in patients with early-stage cervical cancer. Although various classifications were developed in order to define the resection margins of this operation, no clear standardization could be achieved both in the nomenclature and in the extent of the surgery. Total mesometrial resection (TMMR) is a novel procedure which aims to remove all components of the compartment formed by Mullerian duct in which female reproductive organs develop. TMMR differs from the conventional radical hysterectomy techniques in that its surgical philosophy, terminology, and partly resection borders are different. In this paper, a TMMR with therapeutic pelvic lymphadenectomy operation that we performed for the first time with robot-assisted laparoscopic (robotic) approach in an early-stage cervical cancer patient was presented. This procedure has already been described in open surgery by Michael Hockel and translated to the robotic surgery by Rainer Kimmig. Our report is the second paper, to our knowledge, to present the initial experience regarding robotic TMMR in the English literature. PMID- 27195168 TI - Panniculectomy and Cystectomy: An Approach to the Morbidly Obese Patient. AB - The obese patient undergoing radical cystectomy faces a unique set of challenges. We present the case of a 68-year-old gentleman who presented to our institution with Bacillus Calmette-Guerin refractory disease, a body mass index of 38.5, and a large pannus. The present paper describes our technique for performing radical cystectomy with ileal conduit urinary diversion and concomitant panniculectomy. We discuss the impact of obesity on patients undergoing radical cystectomy and how this may be mitigated by panniculectomy. PMID- 27195170 TI - Prevalence and Correlates of Alcohol Use among a Sample of Nigerian Semirural Community Dwellers in Nigeria. AB - Objective. To determine the prevalence and correlates of alcohol use among a sample of Nigerian semirural community dwellers in Nigeria. Methods. In a single arm nonrandomized intervention study, the assessment of baseline hazardous and harmful alcohol use and associated risk factors was conducted in two semirural local government areas of Oyo State, Nigeria, with the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). Participants included 1203 subjects 15 years and older, recruited between October 2010 and April 2011. ASSIST score of 0-10 was classified as lower risk scores, 11-26 as moderate risk, and 27+ as high risk. Results. Prevalence of lifetime alcohol use was 57.9% and current alcohol use was 23.7%. Current alcohol use was more prevalent among the younger age group p = 0.02, male gender p = 0.003, unmarried p < 0.01, low educational level p = 0.003, low socioeconomic class p = 0.01, unemployed p < 0.001, and the Christians p < 0.01. Of the current drinkers, the majority (69.1%) were at either moderate or high health risk from alcohol use. Conclusion. Alcohol consumption is prevalent in semirural communities in Nigeria and the majority of these drinkers are at moderate or high health risk. Screening, brief intervention, and referral for treatment for unhealthy alcohol use should be integrated into community care services in Nigerian rural communities. PMID- 27195169 TI - Leiomyoma in a Renal Allograft. AB - Leiomyomas are smooth muscle tumours that are rarely found in the kidney. There is one report of a leiomyoma in a kidney transplant in a paediatric recipient. Here, we report an adult renal transplant recipient who developed an Epstein-Barr virus-positive leiomyoma in his allograft 15 years after transplantation. The patient was converted to everolimus for posttransplant immunosuppression management and there was no sign of progression over a year. PMID- 27195171 TI - Poor Performance of the Chlamydia Rapid Test Device for the Detection of Asymptomatic Infections in South African Men: A Pilot Study. AB - Background. To the best of our knowledge, there have been no published reports on the diagnostic performance of the Chlamydia Rapid Test (CRT) Device for male urine samples. We evaluated the performance of the CRT Device when compared with that of the BD ProbeTec ET PCR Assay in a population of asymptomatic men. Methods. The study enrolled 100 men between June and July 2015. From each consenting male, 20-30 mL of urine was collected. Sensitivity and specificity of the rapid test compared to PCR were calculated. All analysis was performed in STATA version 13. Results. All men had valid rapid and PCR test results. The test showed a low sensitivity against PCR (20%) (95% CI 3.7-6.2%); however, an excellent specificity was observed (100%) (one sided 97.5% CI: 96.0-100). Conclusions. This test was not found to be suitable as a screening tool for genital Chlamydia infections in men. Our findings emphasize the need for more sensitive POC tests to be developed since the current approach for the management of STIs in Africa is confounded by poor sensitivity and specificity resulting in many infected individuals not being treated. PMID- 27195172 TI - Nonmotor Features in Parkinson's Disease: What Are the Most Important Associated Factors? AB - Introduction. The purpose of this study was to demonstrate the frequency and severity of nonmotor symptoms and their correlations with a wide range of demographic and clinical factors in a large cohort of patients with Parkinson's disease (PD). Methods. 268 PD patients were assessed using the validated Movement Disorders Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS), the Beck Depression Inventory (BDI), Parkinson's Disease Questionnaire (PDQ-39), the Hoehn and Yahr scale (HY), the Schwab and England Activities of Daily Living (SE ADL) Scale, and the Minimental State Examination (MMSE). Results. Nonmotor symptoms had a strong positive relationship with depression and lower quality of life. Also, age, duration and severity of PD, cognitive impairment, daily dose, and duration of levodopa treatment correlated with the burden of nonmotor symptoms. Patients with postural instability and gait disorder (PIGD) dominance or with the presence of motor complications had higher MDS-UPDRS Part I scores expressing the load of nonmotor features, compared to participants with other disease subtypes or without motor complications. Conclusions. Though the severity of individual nonmotor symptoms was generally rated by PD patients as "mild" or less, we found a significant cumulative effect of nonmotor symptoms on patients' mood, daily activities, and quality of life. PMID- 27195173 TI - A FACS Based Case Study on Two HbE-beta Thalassaemia Members of a Family, Having Similar Mutational Background. AB - In this report we have tried to explain the reasons behind the difference in the pattern of transfusion requirement between two members of a family with similar beta-globin mutation. The father and younger son both are HbE-beta, but the father never had transfusion, whereas the younger son takes transfusion monthly. Mother and the elder son are HbEE without any history of transfusion. beta-globin mutations of all family members were determined by ARMS-PCR. These were reconfirmed by direct sequencing of beta-globin gene. Father and younger son were found to be Cod 26 (G-A)/IVS 1-5 (G-C), whereas mother and elder son were found to be Cod 26 (G-A)/Cod 26 (G-A). XmnI sequencing also revealed that all members of the family were CC. Then, flow cytometry study of red blood cells (RBCs) was performed to measure the oxidative stress of the RBCs. This study was also done on the light and dense fractions of the RBC population of the father and younger son. It was seen that the younger son suffers severe oxidative stress, which can be explained by his higher transfusion requirement. From our work, we have established the importance of taking oxidative stress of RBCs into consideration to explain the clinical manifestation and progression of haemoglobin related diseases like thalassaemia. PMID- 27195174 TI - 3D-Printing in Congenital Cardiology: From Flatland to Spaceland. AB - Medical imaging has changed to a great extent over the past few decades. It has been revolutionized by three-dimensional (3D) imaging techniques. Despite much of modern medicine relying on 3D imaging, which can be obtained accurately, we keep on being limited by visualization of the 3D content on two-dimensional flat screens. 3D-printing of graspable models could become a feasible technique to overcome this gap. Therefore, we printed pre- and postoperative 3D-models of a complex congenital heart defect. With this example, we intend to illustrate that these models hold value in preoperative planning, postoperative evaluation of a complex procedure, communication with the patient, and education of trainees. At this moment, 3D printing only leaves a small footprint, but makes already a big impression in the domain of cardiology and cardiovascular surgery. Further studies including more patients and more validated applications are needed to streamline 3D printing in the clinical setting of daily practice. PMID- 27195175 TI - Thermographic Assessment of a Vascular Malformation of the Hand: A New Imaging Modality. AB - Vascular malformations of the hand are rare. Angiography is the current Gold Standard imaging modality. Thermal imaging is an emerging noninvasive, noncontact technology that does not require intravenous contrast agents. We present the case of a patient with an arteriovenous malformation affecting the hand in which thermal imaging has been used as an adjunct to capture baseline images to allow monitoring of progression. We suggest that thermal imaging provides an adjunct that can be used in addition to clinical examination and/or angiography for the diagnosis and routine follow-up of conservatively managed arteriovenous malformations, to monitor progression or vascular steal, and also for recording recurrence after surgical excision for which there is known to be a significant incidence. With the benefit of being a noninvasive imaging modality that does not require intravenous contrast, or ionizing radiation exposure, office-based thermal imaging may become commonplace. PMID- 27195176 TI - Quadricuspid Aortic Valve: A Rare Congenital Cause of Aortic Insufficiency. AB - Quadricuspid aortic valve (QAV) is a rare congenital cardiac anomaly causing aortic regurgitation usually in the fifth to sixth decade of life. Earlier, the diagnosis was mostly during postmortem or intraoperative, but now with the advent of better imaging techniques such as transthoracic echocardiography, transesophageal echocardiography (TEE), and cardiac magnetic resonance imaging, more cases are being diagnosed in asymptomatic patients. We present a case of a 39-year-old male who was found to have QAV, with the help of TEE, while undergoing evaluation for a diastolic murmur. The patient was found to have Type B QAV with moderate aortic regurgitation. We also present a brief review of classification, pathophysiology, and embryological basis of this rare congenital anomaly. The importance of diagnosing QAV lies in the fact that majority of these patients will require surgery for aortic regurgitation and close follow-up so that aortic valve replacement/repair is done before the left ventricular decompensation occurs. PMID- 27195177 TI - Sonographic Appearance of the Median Nerve Following Revision Carpal Tunnel Surgery. AB - The main objective of this pictorial essay is to illustrate the sonographic appearance of the postoperative carpal tunnel and median nerve. Carpal tunnel surgical treatment failures have been shown to occur in up to 19% of a large series requiring re-exploration. Surgical management options for recurrent carpal tunnel syndrome (CTS) include revision release, neurolysis, vein wrapping, and fat grafting procedures. While several descriptions of median nerve entrapment in CTS exist in the ultrasound literature, little is written regarding its postoperative appearance. We report the sonographic changes in the appearance of the median nerve and postoperative carpal tunnel. PMID- 27195178 TI - Mucinous Cystic Neoplasm of the Liver Masquerading as an Echinococcal Cyst: Radiologic-pathologic Differential of Complex Cystic Liver Lesions. AB - Although simple liver cysts are common, complex cystic liver lesions are infrequent and represent a diagnostic and therapeutic challenge. The differential diagnosis of complex cystic liver lesions can be grouped into neoplastic, infectious or inflammatory, and miscellaneous pathologic entities. Clinicians should remember to consider mucinous cystic neoplasm and echinococcal cysts in the differential, which are uncommon etiologies for liver lesions but may expose unique challenges. We present a case of a 49-year-old female who was referred for evaluation of a new complex cystic liver lesion. The following brief review describes how radiologic imaging and pathologic testing can help distinguish between the broad spectrum of diseases that may produce cystic liver lesions. PMID- 27195179 TI - Rare Intensely Fluorine-18-fluorodeoxyglucose Avid Large Retropharyngeal Goiter in a Patient with Invasive Breast Carcinoma. AB - Diffuse increased fluorine-18-fluorodeoxyglucose ((18)F-FDG) avidity on positron emission tomography (PET) scans has been demonstrated in patients with chronic thyroiditis, likely secondary to increased inflammatory cell glucose uptake. A complex association has been demonstrated between breast cancer and thyroid disease, although the mechanism remains elusive. Development of chronic thyroiditis and/or goiter in breast cancer patients has been suggested to convey a more favorable prognosis. Goiter extension is almost exclusively into retrosternal space, with only a handful of cases reported with superior extension into retropharyngeal space. We present a rare case of a diffusely enlarged goiter extending superior and posterior into the retropharyngeal space with an associated intense (18)F-FDG avidity standardized uptake value maximum (SUVmax) of 16.1 in a patient with invasive ductal breast cancer. To our knowledge, this represents the first published case of diffusely (18)F-FDG avid goiter with retropharyngeal extension. PMID- 27195180 TI - Dedicated Three-dimensional Breast Computed Tomography: Lesion Characteristic Perception by Radiologists. AB - OBJECTIVES: To assess radiologist confidence in the characterization of suspicious breast lesions with a dedicated three-dimensional breast computed tomography (DBCT) system in comparison to diagnostic two-dimensional digital mammography (dxDM). MATERIALS AND METHODS: Twenty women were recruited who were to undergo a breast biopsy for a Breast Imaging-Reporting and Data System (BI RADS) 4 or 5 lesion evaluated with dxDM in this Institutional Review Board approved study. The enrolled subjects underwent imaging of the breast(s) of concern using DBCT. Seven radiologists reviewed the cases. Each reader compared DBCT to the dxDM and was asked to specify the lesion type and BI-RADS score for each lesion and modality. They also compared lesion characteristics: Shape for masses or morphology for calcifications; and margins for masses or distribution for calcifications between the modalities using confidence scores (0-100). RESULTS: Twenty-four biopsied lesions were included in this study: 17 (70.8%) masses and 7 (29.2%) calcifications. Eight (33.3%) lesions were malignant, and 16 (66.7%) were benign. Across all lesions, there was no significant difference in the margin/distribution (Delta = -0.99, P = 0.84) and shape/morphology (Delta = 0.10, P = 0.98) visualization confidence scores of DBCT in relation to dxDM. However, analysis by lesion type showed a statistically significant increase in reader shape (Delta =11.34, P = 0.013) and margin (Delta =9.93, P = 0.023) visualization confidence with DBCT versus dxDM for masses and significant decrease in reader morphology (Delta = -29.95, P = 0.001) and distribution (Delta = -28.62, P = 0.002) visualization confidence for calcifications. CONCLUSION: Reader confidence in the characterization of suspicious masses is significantly improved with DBCT, but reduced for calcifications. Further study is needed to determine whether this technology can be used for breast cancer screening. PMID- 27195181 TI - "Reverse Tigroid" Pattern in Pachygyria: A Novel Finding. AB - Pachygyria is considered a subtype of lissencephaly which, in turn, is a spectrum of disorders caused by abnormal neuronal migration. Clinical presentation in this disorder may be varied including microcephaly, developmental delay, facial dysmorphism, seizures, and mental retardation. Magnetic resonance imaging (MRI) of brain identifies the exact nature and extent of the disease and helps in delineating further plan of management. A Tigroid pattern on axial MRI scan and leopard pattern on a sagittal plane has been classically reported in disorders of myelin formation such as metachromatic leukodystrophy and Pelizaeus-Merzbacher disease. We present here a case of pachygyria who presented to us with some atypical features including "tigroid-like stripes" and "leopard-like pattern" on MRI brain which has not been reported in the medical literature previously. PMID- 27195182 TI - Dermatofibrosarcoma Protuberans: Insights into a Rare Soft Tissue Tumor. AB - Dermatofibrosarcoma protuberans (DFSP) is a rare soft tumor which originally represents a cutaneous sarcoma. It grows slowly and presents usually as nodular superficial lesion on the trunk or the extremities. Although these tumors are locally aggressive with high rate of recurrence following surgery; the prognosis is considered excellent when it is effectively treated. The radiological appearance of this tumor has rarely been studied and findings infrequently discussed in the literature probably because many lesions underwent resection before imaging. Although imaging is infrequently performed for this lesion; it can show characteristic features and demonstrate the full extent. Imaging may also play a role in the differentiation of this tumor from more serious soft tissue lesions such as more aggressive sarcomas and hemangioma. In this article, we discuss the imaging findings of DFSP that can aid in its diagnosis and its variable appearances. In addition; the clinical presentation and treatment options are also described with review of the previous literature. PMID- 27195184 TI - Multiparametric Magnetic Resonance Imaging of Recurrent Prostate Cancer. AB - Multiparametric magnetic resonance (MR) imaging of the prostate combines both morphological and functional MR techniques by utilizing small field of view T1 weighted, T2-weighted, diffusion-weighted imaging, dynamic contrast-enhanced imaging, and MR spectroscopy to accurately detect, localize, and stage primary and recurrent prostate cancer. Localizing the site of recurrence in patients with rising prostate-specific antigen following treatment affects decision making regarding treatment and can be accomplished with multiparametric prostate MR. Several different treatment options are available for prostate cancer including radical prostatectomy, external beam radiation therapy, brachytherapy, androgen deprivation therapy, or a number of focal therapy techniques. The findings of recurrent prostate cancer can be different depending on the treatment the patient has received, and the radiologist must be able to recognize the variety of imaging findings seen with this common disease. This review article will detail the findings of recurrent prostate cancer on multiparametric MR and describe common posttreatment changes which may create challenges to accurate interpretation. PMID- 27195185 TI - Translation in Data Mining to Advance Personalized Medicine for Health Equity. AB - Personalized medicine is the development of 'tailored' therapies that reflect traditional medical approaches, with the incorporation of the patient's unique genetic profile and the environmental basis of the disease. These individualized strategies encompass disease prevention, diagnosis, as well as treatment strategies. Today's healthcare workforce is faced with the availability of massive amounts of patient- and disease-related data. When mined effectively, these data will help produce more efficient and effective diagnoses and treatment, leading to better prognoses for patients at both the individual and population level. Designing preventive and therapeutic interventions for those patients who will benefit most while minimizing side effects and controlling healthcare costs, requires bringing diverse data sources together in an analytic paradigm. A resource to clinicians in the development and application of personalized medicine is largely facilitated, perhaps even driven, by the analysis of "big data". For example, the availability of clinical data warehouses is a significant resource for clinicians in practicing personalized medicine. These "big data" repositories can be queried by clinicians, using specific questions, with data used to gain an understanding of challenges in patient care and treatment. Health informaticians are critical partners to data analytics including the use of technological infrastructures and predictive data mining strategies to access data from multiple sources, assisting clinicians' interpretation of data and development of personalized, targeted therapy recommendations. In this paper, we look at the concept of personalized medicine, offering perspectives in four important, influencing topics: 1) the availability of 'big data' and the role of biomedical informatics in personalized medicine, 2) the need for interdisciplinary teams in the development and evaluation of personalized therapeutic approaches, and 3) the impact of electronic medical record systems and clinical data warehouses on the field of personalized medicine. In closing, we present our fourth perspective, an overview to some of the ethical concerns related to personalized medicine and health equity. PMID- 27195183 TI - Hip Arthroplasty Pseudotumors: Pathogenesis, Imaging, and Clinical Decision Making. AB - Pseudotumors are a complication of hip arthroplasty. The goal of this article is to review the clinical presentation, pathogenesis, histology, and the role of diagnostic imaging in clinical decision making for treatment, and surveillance of pseudotumors. We will discuss the multimodal imaging appearances, differential diagnosis, associated complications, treatment, and prognosis of pseudotumors, as an aid to the assessment of orthopedic prostheses at the hip. PMID- 27195186 TI - C-C chemokine receptor type-4 transduction of T cells enhances interaction with dendritic cells, tumor infiltration and therapeutic efficacy of adoptive T cell transfer. AB - T cell infiltration at the tumor site has been identified as a major predictor for the efficacy of adoptive T cell therapy. The chemokine C-C motif ligand 22 (CCL22) is highly expressed by immune cells in murine and human pancreatic cancer. Expression of its corresponding receptor, C-C chemokine receptor type 4 (CCR4), is restricted to regulatory T cells (Treg). We show that transduction of cytotoxic T cells (CTL) with CCR4 enhances their immigration into a pancreatic cancer model. Further, we show that binding of CCR4 with CCL22 strengthens the binding of T cell LFA-1 to dendritic cell (DC) ICAM-1 and increases CTL activation. In vivo, in a model of subcutaneous pancreatic cancer, treatment of tumor-bearing mice with CCR4-transduced CTL led to the eradication of established tumors in 40% of the mice. In conclusion, CCR4 overexpression in CTL is a promising therapeutic strategy to enhance the efficacy of adoptive T cell transfer (ACT). PMID- 27195188 TI - Cardiac manifestations of idiopathic pulmonary fibrosis. AB - Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, parenchymal disease of the lung with an estimated prevalence of 14-43 per 100,000. Patient usually presents with coughing and exertional dyspnea, which can lead to acute respiratory failure. IPF has been associated with various co-morbidities such as lung cancer, emphysema, obstructive sleep apnea (OSA), GERD and multiple cardiovascular consequences. The cardiovascular manifestations of IPF include pulmonary hypertension, heart failure, coronary artery disease, cardiac arrhythmias & cardiac manifestations of drugs used to treat IPF. This review will outline evidence of the association between IPF and cardiovascular conditions and attempt to provide insights into the underlying pathophysiology. We also discuss the impact of these cardiovascular diseases on patients with IPF including increased morbidity and mortality. PMID- 27195187 TI - Granulomatosis with polyangiitis (Wegener's disease): An updated review of ocular disease manifestations. AB - Granulomatosis with polyangiitis (GPA) is a potentially lethal systemic disorder that is characterized by necrotizing vasculitis of small arteries and veins. The respiratory system is most commonly affected in limited forms of the disease, however upper and lower respiratory system, systemic vasculitis, and necrotizing glomerulonephritis are the characteristic components of the disease triad. The peak incidence is observed at 64-75 years of age, with a prevalence of 8-10 per million depending on geographic location. In this review we focus on the ocular manifestations of the disease which occur in nearly in one third of the patients. In addition we describe the neuro-ophthalmic complications which occur in up to half of cases. We also discuss the current systemic treatment options including corticosteroids, cyclophosphamide, azathioprine, and the available biologic response modifiers including rituximab. The disease remains difficult to diagnose due to the generalized symptomatic presentation of patients with GPA. As a result, several sets of diagnostic criteria have been developed which include clinical, serological, and histopathological findings to varying extents. Early diagnosis and multi-specialty collaboration among physicians is necessary to adequately manage the disease and the potential complications that may result from drugs used in the treatment of the disease. Despite recent advances, more research is necessary to prevent the high rates of mortality from the disease itself and from therapeutic side effects. PMID- 27195190 TI - Evaluation of quality of life in individuals with severe chronic motor disability: A major challenge. AB - Diverse conditions causing a very heavy and chronic motor disability, such as an advanced amyotrophic lateral, advanced form of multiple sclerosis, high spinal cord injury or a locked-in syndrom, are now getting better medical care and benefit of life support technology with consequent prolonged survival. Quality of life (QoL) assessment is being considered increasingly important to globally apprehend their general well-being. However, the motor disability that affects them appears as a substantial limitation for the assessment of their QoL and consequently a major challenge for all the community that carries an interest for them. This review discussed several avenues to provide to patients and caregivers, clinicians and researchers, and health decision making authority: i) elements to determine the most appropriate QoL measure with regard to the interest of patient's point of view, the QoL instruments suitable for this category of patients and their acceptability, ii) some arguments of the clinical relevance and accuracy of QoL assessment: interpretations of the questionnaires, QoL determinants, particularity of QoL evaluation for individuals with cognitive impairment and the caregivers perceptions of patients QoL. In conclusion, evaluation of QoL in patients with severe chronic motor handicap is a challenge of major interest, with major ethical issues. It needs to use adapted QoL scales and longitudinal following because of adaptive phenomena to the degree of handicap. PMID- 27195189 TI - The progress of early growth response factor 1 and leukemia. AB - Early growth response gene-1 (EGR1) widely exists in the cell nucleus of such as, zebrafish, mice, chimpanzees and humans, an it also can be observed in the cytoplasm of some tumors. EGR1 was named just after its brief and rapid expression of different stimuli. Accumulating studies have extensively demonstrated that the widespread dysregulation of EGR1 is involved in hematological malignancies such as human acute myeloid leukemia (AML), chronic myelogenous leukemia, chronic lymphocytic leukemia, multiple myeloma, and B cell lymphoma. With the deep research on EGR1, its expression, function and regulatory mechanism has been gradually elucidated, and provides more possibilities for treatment strategies of patients with leukemia. Herein, we summarize the roles of EGR1 in its biological function and relationship with leukemia. PMID- 27195192 TI - Fever as an important resource for infectious diseases research. AB - Fever or pyrexia is a process where normal body temperature is raised over homeostasis conditions. Although many effects of fever over the immune system have been known for a long time, it has not been until recent studies when these effects have been evaluated in several infection processes. Results have been promising, as they have reported new ways of regulation, especially in RNA molecules. In light of these new studies, it seems important to start to evaluate the effects of pyrexia in current research efforts in host-pathogen interactions. Viruses and bacteria are responsible for different types of infectious diseases, and while it is of paramount importance to understand the mechanisms of infection, potential effects of fever on this process may have been overlooked. This is especially relevant because during the course of many infectious diseases the organism develops fever. Due to the lack of specific treatments for many of those afflictions, experimental evaluation in fever-like conditions can potentially bring new insights into the infection process and can ultimately help to develop treatments. The aim of this review is to present evidence that the temperature increase during fever affects the way the infection takes place, for both the pathogen and the host. PMID- 27195191 TI - Role of metabolism during viral infections, and crosstalk with the innate immune system. AB - Viruses have been for long polemic biological particles which stand in the twilight of being living entities or not. As their genome is reduced, they rely on the metabolic machinery of their host in order to replicate and be able to continue with their infection process. The understanding of their metabolic requirements is thus of paramount importance in order to develop tailored drugs to control their population, without affecting the normal functioning of their host. New advancements in high throughput technologies, especially metabolomics are allowing researchers to uncover the metabolic mechanisms of viral replication. In this short review, we present the latest discoveries that have been made in the field and an overview of the intrinsic relationship between metabolism and innate immunity as an important part of the immune system. PMID- 27195193 TI - Inflammageing assessed by MMP9 in normal Japanese individuals and the patients with Werner syndrome. AB - Age-associated minor inflammation: inflammageing may explain human ageing mechanism(s). Our previous study reported a significant increase in the serum level of highly sensitive C-reactive protein (hsCRP) with normal ageing and the patients with Werner syndrome (WS). To further study the minor inflammatory condition associated with ageing, another possible ageing biomarker: matrix metalloproteinase-9 (MMP9) was examined in the sera from 217 normal Japanese individuals aged between 1 and 100 years and 41 mutation-proven Japanese WS aged between 32 and 70 years. MMP9 was assayed by ELISA. The serum level of MMP9 was elevated significantly (p < 0.001) with normal ageing from both sexes as hsCRP. In contrast to normal ageing, the serum MMP9 level in WS decreased significantly with calendar age (p < 0.05). The MMP9 level (ng/mL) in WS (147.2 +/- 28.5) was not significantly different in comparison with those from age-matched normal adult population aged between 25 and 70 years (109.1 +/- 9.4), nor normal elderly population aged between 71 and 100 years (179.9 +/- 16.1). Although both normal ageing and WS were associated with minor inflammation, the inflammatory parameters such as serum MMP9 and hsCRP changed differently between normal ageing and WS. The WS-specific chronic inflammation including skin ulcer and diabetes mellitus may contribute the different behavior of both ageing biomarkers from normal ageing. PMID- 27195194 TI - Dietary supplement use and nosebleeds in hereditary haemorrhagic telangiectasia - an observational study. AB - Understanding potential provocations of haemorrhage is important in a range of clinical settings, and particularly for people with abnormal vasculature. Patients with hereditary haemorrhagic telangiectasia (HHT) can report haemorrhage from nasal telangiectasia in real time, and suggested dietary factors may precipitate nosebleeds. To examine further, nosebleed severity, dietary supplement use, and blood indices were evaluated in an unselected group of 50 HHT patients recruited from a specialist UK service. Using the validated Epistaxis Severity Score, nosebleed severity ranged from 0 to 9.1 out of 10 (median 3.9). Using a Food Frequency Questionnaire, 24/50 (48%) participants reported use of dietary supplements in the previous year. A third (18/50; 36%) had used self prescribed, non-iron containing dietary supplements, ingesting between 1 and 3 different supplements each day. Eight (16%) used fish oils. Despite having more severe epistaxis (p = 0.012), the 12 iron supplement users had higher serum iron concentrations, and were able to maintain their red blood cell indices. In contrast, there was no evident benefit for the participants using non iron supplements. Furthermore, platelet counts and serum fibrinogen tended to be lower in fish oil/supplement users, and one fish oil user demonstrated reduced in vitro platelet aggregation. In conclusion, in this small study, a third of HHT patients used non-iron dietary supplements, and one in six ingested fish oils, unaware of their known anti-platelet activity. The scale of use, and potential of these "natural health supplements" to exacerbate nosebleeds has not been appreciated previously in HHT. PMID- 27195195 TI - The retrieval of atrial septal defect closure device embolized into aortic arch. AB - Percutaneous atrial septal defect (ASD) closure has become an increasingly simplified procedure over the past decade. The device embolization is seen rarely but it can be fatal. Although percutaneous retrieval is feasible, surgical removal might be preferred when the endothelialization status of the device is unknown. We report a comlication of such closure in a 43-year-old woman: embolization of the ASD occluder device into aortic arch 12 months after implantation. We removed the device surgically and closed the ASD. PMID- 27195196 TI - Cleidocranial dysplasia: A report of two cases with brief review. AB - Cleidocranial dysplasia (CCD) is a genetic disorder primarily causing dysplasia of bones and teeth with autosomal dominant inheritance pattern. Affected individuals presented with several skeletal and dental abnormalities mainly hypoplasia of clavicles, open fontanelles, short stature, retention of primary teeth, supernumerary teeth, delayed eruption of permanent teeth, multiple impacted permanent teeth etc. The present series of two cases illustrates the clinical and radiological features of pediatric patients with cleidocranial dysplasia. The early diagnosis of the condition helps in proper orientation of the treatment thereby offering better quality of life to such patients. PMID- 27195197 TI - A case of split notochord syndrome: Presenting with respiratory failure in the neonatal period. AB - Split notochord syndrome (SNS) is a very rare congenital anomaly. This report describes a male newborn with a neuroenteric cyst in the posterior mediastinum and multiple vertebrae anomalies presenting with respiratory failure and pulmonary hypertension. This report also discusses the embryological development and the etiologic theories of SNS. PMID- 27195198 TI - Infantile systemic hyalinosis: Report of two severe cases from Saudi Arabia and review of the literature. AB - Infantile systemic hyalinosis (ISH) (OMIM 228600) is a rare fatal autosomal recessive disorder characterized by extensive deposition of hyaline material in many tissues. Consanguinity has been recorded in many cases. Herein we present two new Saudi cases with review of the literature. Our first proband was a 9 month-old male who was the first baby for parents descended from a closed consanguineous pedigree. The second proband was a 13 month-old male who was the first baby for consanguineous parents (3(rd) C). Both cases presented with bilateral painful limited limb movement with joints contractures, low birth weight (< P5), severe generalized stiff skin, hyper-pigmented skin over bony prominences, fleshy perianal masses and gingival hypertrophy. The first child died at 18(th) month as a result of recurrent chest infections. The second proband showed a severe progressive course of joint contractures, and died at 19(th) month because of failure to thrive and recurrent infections. Although the clinical features of ISH are characteristic, the disease is under/miss diagnosed. The role of consanguinity needed to be highlighted to the community. Careful clinical examination and molecular diagnosis will be helpful for genetic counseling, prenatal diagnosis and early treatment. PMID- 27195199 TI - Fibro-epithelial polyps in children: A report of two cases with a literature review. AB - A fibro-epithelial polyp is the most common epithelial benign tumor of the oral cavity. Such a polyp is of mesodermal origin and it is a pink, red, or white knob like painless growth that is sessile or pedunculated. A fibro-epithelial polyp commonly occurs on buccal mucosa, the tongue, or the gingiva. A fibro-epithelial polyp is an inflammatory hyperplastic lesion in response to chronic irritation due to calculus, sharp tooth edges, irregular denture borders, or overhanging restorations. Such a polyp rarely occurs before the fourth decade of life and its prevalence is not sex-specific. The current paper presents two cases where an intraoral fibro-epithelial polyp was successfully managed in children. Conservative surgical excision was performed in both cases. A follow-up at 3 months revealed uneventful healing of the site without reoccurrence of the lesion. PMID- 27195200 TI - Tip of nose tuberculosis: A rare presentation of extra pulmonary tuberculosis. AB - Tuberculosis is notorious that it affects various sites of the human body and presents in different ways. One of the uncommon or rather rare presentation of extra pulmonary tuberculosis is nasal tuberculosis. The nose apart from its physiological functions also contributes to facial aesthetics and gives a defined appearance and its deformity imparts cosmetic disfigurement and unsightly appearance. Both primary and secondary forms of nasal tuberculosis are rare but should be considered in the differential diagnosis of ulcerative or crusting lesions of the nose. Here we report such a case of nasal tuberculosis, which presented as an ulcerative and crusting lesion over the tip of the nose in a female child. The patient was given antituberculous chemotherapy after establishing the diagnosis and responded well to treatment. PMID- 27195201 TI - New perspective on molecular markers as promising therapeutic targets in germ cell tumors. AB - Testicular germ cell tumors (TGCTs) are the most frequent solid malignant tumors in men 20-40 years of age and the most frequent cause of death from solid tumors in this age group. TGCTs comprise two major histologic groups: seminomas and non seminomas germ cell tumors (NSGCTs). NSGCTs can be further divided into embryonal carcinoma, Teratoma, yolk sac tumor, and choriocarcinoma. Seminomas and NSGCTs present significant differences in clinical features, therapy, and prognosis, and both show characteristics of the Primordial Germ Cells (PGCs). Many discovered biomarkers including HMGA1, GPR30, Aurora-B, estrogen receptor beta, and others have given further advantages to discriminate between histological subgroups and could represent useful therapeutic targets. PMID- 27195202 TI - Causal discovery and inference: concepts and recent methodological advances. AB - This paper aims to give a broad coverage of central concepts and principles involved in automated causal inference and emerging approaches to causal discovery from i.i.d data and from time series. After reviewing concepts including manipulations, causal models, sample predictive modeling, causal predictive modeling, and structural equation models, we present the constraint based approach to causal discovery, which relies on the conditional independence relationships in the data, and discuss the assumptions underlying its validity. We then focus on causal discovery based on structural equations models, in which a key issue is the identifiability of the causal structure implied by appropriately defined structural equation models: in the two-variable case, under what conditions (and why) is the causal direction between the two variables identifiable? We show that the independence between the error term and causes, together with appropriate structural constraints on the structural equation, makes it possible. Next, we report some recent advances in causal discovery from time series. Assuming that the causal relations are linear with nonGaussian noise, we mention two problems which are traditionally difficult to solve, namely causal discovery from subsampled data and that in the presence of confounding time series. Finally, we list a number of open questions in the field of causal discovery and inference. PMID- 27195203 TI - Plagiarism in dentistry. PMID- 27195204 TI - Effect of topical simvastatin (1.2 mg) on gingival crevicular fluid interleukin 6, interleukin-8 and interleukin-10 levels in chronic periodontitis - A clinicobiochemical study. AB - OBJECTIVES: The impact of simvastatin (SMV), a cholesterol lowering drug, on bone metabolism appears to involve complex interaction with cholesterol metabolites, hormones, inflammatory mediators and growth factors, thus having direct influence on extent and severity of periodontitis. The present study aims to evaluate the in vivo effect of subgingivally delivered SMV gel (1.2 mg) as a local drug delivery agent on clinical parameters and on interleukin-6 (IL-6), interleukin-8 (IL-8) and interleukin-10 (IL-10) levels in gingival crevicular fluid (GCF) of chronic periodontitis patients. MATERIALS AND METHODS: 50 patients were selected and categorized into two treatment groups: control (scaling and root planing) and test group (scaling and root planing with SMV gel). At initial appointment, clinical parameters were measured. Biochemical analysis of GCF samples was done to evaluate the amount of IL-6, IL-8 and IL-10. GCF sampling and clinical parameters were repeated at one and three months for both the groups. RESULTS: SMV has an inhibitory effect on pro-inflammatory cytokines (IL-6, IL-8) and stimulatory effect on anti-inflammatory cytokines (IL-10) in GCF of periodontitis patients and has significantly positive effect on all clinical parameters except relative attachment level (RAL). The addition of SMV, thereby, further alters the levels of cytokine that reflect enhanced antibacterial host defence activity at that site. CONCLUSION: Topical SMV has a beneficial effect on periodontal health. Removal of the bacterial plaque and subgingival delivery of SMV significantly modulates the chemokines present in GCF. To summarize, SMV shows promising role in the management of periodontitis. PMID- 27195205 TI - Keratocystic odontogenic tumors related to Gorlin-Goltz syndrome: A clinicopathological study. AB - BACKGROUND: Assess clinicopathological features of patients with keratocystic odontogenic tumor (KCOT) associated with Gorlin-Goltz syndrome in our institution from 2004 to 2015. METHOD: After histopathological analyses of KCOT related to Gorlin-Goltz syndrome, 7 patients were assessed. These patients presented a total of 15 primary and 2 recurrent KCOT. RESULTS: All patients presented a multiple KCOT, and 13 lesions were located in mandible (77%) and 4 (23%) in maxilla. Most of the tumors presented a unilocular pattern (71%) and had tooth association (88%). Four patients (57%) were in the age group of 10-19 years and three patients (43%) were in the age group of 20-29 years. There were four male and three female patients. CONCLUSION: KCOT is a frequent manifestation of Gorlin Goltz syndrome and can be its first sign, mainly in young patients. The four patients presented with two lesions (57%) and three lesions in three patients (43%). PMID- 27195206 TI - Management of pediatric mandibular fractures using bioresorbable plating system - Efficacy, stability, and clinical outcomes: Our experiences and literature review. AB - AIMS: The purpose of this study was to determine the efficacy and stability of the biodegradable fixation system for treatment of mandible fractures in pediatric patients by measuring the bite force. METHODS: Sixty pediatric patients with mandibular fractures (36 males, 24 females) were included in this study. The 2.5-mm resorbable plates were adapted along Champy's line of ideal osteosynthesis and secured with four 2.5 mm diameter monocortical resorbable screws, 8 mm in length. All patients were followed for 10 months. Clinical parameters, such as soft tissue infection, nonunion, malunion, implant exposure, malocclusion, nerve injury, and bite force for stability, were prospectively assessed. RESULTS: Adequate fixation and primary bone healing was achieved in 100% of the cases. Six minor complications (10%) were observed: 2 soft tissue infections (3%), 1 plate dehiscence (2%), 1 malocclusion (2%), and 2 paresthesia (3%). CONCLUSION: 2.5-mm resorbable plating system along Champy's line of ideal osteosynthesis is a good treatment modality for mandible fractures in pediatric patients. PMID- 27195207 TI - Silicone vs temporalis fascia interposition in TMJ ankylosis: A comparison. AB - OBJECTIVE: Temporomandibular joint ankylosis (TMJa) is a distressing condition, but can be surgically managed by gap or interpositional arthroplasty, with an aim to restore joint function and prevent re-ankylosis. The aim of this paper is to compare two interposition materials used in management of TMJ ankylosis. METHODS: 15 patients with TMJa were randomly allocated to two groups: group A (n = 6), interposition material used was medical-grade silicon elastomer, and group B (n = 9) where the interposition material used was temporalis fascia. Patients were followed up at regular intervals of 1 and 2 weeks, 1 month, 3 months, and 6 months and were assessed on following parameters: pain by VAS Scale, maximal mouth opening (MMO), implant rejection, and recurrence. RESULTS: The results showed a loss of 4.6% and 7.9% in maximal interincisal mouth opening at 3rd and 6th months in Group A while Group B had a mean loss of 9% and 10% at 3rd and 6th months respectively without any significant difference. None of our cases showed recurrence or implant rejection. CONCLUSION: We conclude that silicone is comparable to temporalis fascia in terms of stability, surgical ease, and adaptability. It not only restores the function of mandible and ensures good maximum interincisal opening but also maintains the vertical ramal height. Also, it requires less operating time and is easy to handle but is not economical. It might be an effective way to restore function and prevent re-ankylosis. PMID- 27195208 TI - Comparative study of nonabsorbable and absorbable barrier membranes in periodontal osseous defects by guided tissue regeneration. AB - BACKGROUND: Periodontal invasion of furcation area in multirooted teeth represents one of the most demanding therapeutic challenges in periodontics. Furcation therapy includes various treatment modalities like either maintenance or elimination of furcation or increased access to furcation area. Recent treatment modalities include regenerative procedures like placement of different type of bone grafts with nonabsorbable or absorbable barrier membranes, through guided tissue regeneration. This study compared the clinical efficacy of nonabsorbable barrier membrane with absorbable membrane when used with hydroxyapatite bone graft (G-Graft) in grade II buccal furcation defects in mandibular 1st molars. MATERIALS AND METHODS: Fourteen subjects with bilateral grade II buccal furcation defects in lower 1st molars were selected and treated in a split-mouth design. After phase I therapy, molars were divided randomly into two groups for the treatment with either resorbable or nonresorbable membrane in conjunction with G-Graft in both groups. RESULTS: All the clinical parameters recorded showed statistically significant improvement in both the groups but no significant difference between two groups was observed. CONCLUSION: Both nonabsorbable and absorbable barrier membranes were equally effective in treating grade II buccal furcation defects in lower molars when used in conjunction with G Graft except with respect to horizontal bone fill in which absorbable barrier membrane showed better results. PMID- 27195209 TI - Child abuse: Cross-sectional survey of general dentists. AB - BACKGROUND: Child abuse continues to be a social menace causing both physical and emotional trauma to benevolent children. Census has shown that nearly 50-75% of child abuse include trauma to mouth, face, and head. Thus, dental professionals are in strategic position to identify physical and emotional manifestations of abuse. AIM: A cross-sectional survey was undertaken to assess knowledge and attitude of dental practitioners regarding child abuse and to identify the barriers in reporting the same. METHODS: With prior consent, a 20-question survey including both multiple choice and dichotomous (Yes/No) questions was mailed to 120 state-registered general dentists, and the data collected were subjected to statistical analysis. RESULTS: Overall response rate to the questionnaires was 97%. Lack of knowledge about dentist's role in reporting child abuse accounted to 55% in the reasons for hesitancy to report. Pearson chi-square test did not show any significant difference between male and female regarding reason for hesitancy to report and legal obligation of dentists. CONCLUSION: Although respondent dentists were aware of the diagnosis of child abuse, they were hesitant and unaware of the appropriate authority to report. Increased instruction in the areas of recognition and reporting of child abuse and neglect should be emphasized. PMID- 27195210 TI - Prevalence and subjective knowledge of tongue lesions in an Indian population. AB - AIM: The current study was designed to determine prevalence of various tongue lesions and their association with age, gender, systemic illness, deleterious habits, and distribution over the surfaces of tongue. It also explored the awareness and knowledge of subjects in relation to presence of tongue lesions, etiological factor, symptoms, and treatment received if any. METHODS: The present study was conducted on 1360 randomly selected dental outpatients from 1/10/2013 to 30/09/2014. Examination of tongue included surface changes, size, movements, and the presence of mucosal lesions. The subjects were asked about the knowledge, symptoms, and treatment obtained in case of awareness regarding the lesion. RESULTS: The prevalence of tongue lesions was found to be 13.75%. The most prevalent lesion was found to be coated tongue. The majority of the lesions were located on dorsum of tongue and not related with age, gender, habit, and systemic condition. A considerable number of subjects were aware of the changes on their tongue but negligible number sought any treatment. CONCLUSIONS: The presence of tongue lesions in the study population was found be significant. Hence, general dental practitioners and health care providers should be educated about the diagnosis, etiology, investigations, and proper management of such tongue lesions. PMID- 27195211 TI - Design of a protocol for obtaining genomic DNA from saliva using mouthwash: Samples taken from patients with periodontal disease. AB - BACKGROUND: Obtaining high quality genomic DNA safely and economically is vital for diverse studies of large populations aimed at evaluating the role of genetic factors in susceptibility to disease. AIM: This study was to test a protocol for the extraction of high quality genomic DNA from saliva samples obtained with mouthwash and taken from patients with periodontal disease. METHODS: Saliva samples were taken from 60 patients and then stored at room temperature. DNA extraction was carried out at distinct post-sampling times (10, 20 and 30 days). Evaluation of genomic DNA was performed with spectrophotometry, electrophoresis, and PCR genotyping and sequencing. RESULTS: The greatest concentration of DNA obtained was 352 MUg at 10 days post-sampling, followed by 121.025 MUg and 19.59 MUg at 20 and 30 days, respectively. When determining the purity of DNA with the spectrophotometric ratio of 260/230, the relations of 1.20, 1.40 and 0.781 were obtained for 10, 20 and 30 days, respectively. In all samples, it was possible to amplify the product of 485 bp and the sequence of the amplicons showed 95% similarity to the reference sequence. CONCLUSION: The present protocol represents an easy, safe and economical technique for obtaining high quality genomic DNA. PMID- 27195212 TI - Evaluation of different diagnostic criteria of diseases manifesting the oral cavity - A review. Part-1. AB - There are many disorders affecting the oral cavity, which can cause difficulty in diagnosis for an oral physician. A criterion is defined as 'a principle or standard by which something may be judged or decided'. Several criteria have been given by different authors or committee, which further aids in diagnosis of certain disease. This article encompasses a collection and analysis of all the criteria of diseases affecting the oral cavity, which will be beneficial for an oral physician in their routine clinics. PMID- 27195213 TI - Should the orthodontic brackets always be removed prior to magnetic resonance imaging (MRI)? AB - Request for temporary removal of orthodontic appliances due to medical conditions that require magnetic resonance (MR) imaging is not uncommon in daily practice in the field of orthodontics. This may be at the expense of time and cost. Metal Orthodontic appliances cause more signal loss and image distortion as compared to ceramic and titanium ones. Stainless steel and large brackets in addition to the oriented miniscrews in relation to the axis of magnetic field may cause severe signal loss and image distortion. Moreover, gradient echo and frequency-selective fat saturation MR protocols are more susceptible to metal artifacts. The spin echo and fat-suppression protocols, low magnetic field strength (e.g., 1.5 Tesla vs. 3 Tesla), small field of view, high-resolution matrix, thin slice, increased echo train length and increased receiver band width could be applied to lessen the metal artifacts in MR images. The larger the distance between an appliance and desired location to be imaged, the lower the distortion and signal loss. Decision to remove brackets should be made based on its composition and desired anatomic location. In this review, first the principles of MR imaging are introduced (Part-I) and then the interactions of orthodontic appliances and magnetic field are farther discussed (Part-II). PMID- 27195215 TI - Spindle cell carcinoma of the mandible: Clinicopathological and immunohistochemical characteristics. AB - Spindle cell carcinoma, a rare variant of squamous cell carcinoma, has propensity to occur in the upper aero digestive tract, including the oral mucosa. In this oral pathology communication, we report the occurrence of this neoplasm in the left mandible as a large fleshy growth with destruction of bone in a 73-year-old Afro-Trinidadian female. The distinction of this tumor from other malignant spindle cell mesenchymal tumors is important. Selective sampling of this specimen for possible transitional areas of squamous and spindle cell appearance, immunohistochemical staining for cytokeratin, vimentin, and S-100 protein are helpful in establishing the diagnosis. According to the patient's insistence, debulking of the tumor was performed under general anesthesia. Eight months later the patient succumbed to the disease. PMID- 27195216 TI - Adenoid cystic carcinoma: A rare late presentation of the mobile tongue. AB - Adenoid cystic carcinoma (ACC) is an infrequent malignant neoplasm of the salivary glands. We present a case of a 70-year-old male patient with a swelling over the dorsal and ventral surface of anterior two third of the tongue which was causing him difficulty in mastication since 10 months. Ultrasound and magnetic resonance imaging were done following which the surgical excision of the lesion was performed and histopathological diagnosis of ACC was achieved. It was rare to find ACC in such an old man with such a large lesion presenting so late in the rare site of the mobile tongue. ACC is a slowly growing, highly invasive cancer with a high recurrence rate and chances of metastases, so surgery is the choice of treatment with mandatory long-term follow-up. PMID- 27195217 TI - A rare case of angiofibroma of the mandible: A case report. AB - Angiofibroma is a rare, highly vascular nonencapsulated tumor, which is locally invasive. A rare case of angiofibroma of the mandible in a 16-year-old female patient is reported here. The lesion was excised along with surgical removal of right mandibular third molar tooth. Patient was followed up for 1 year without any recurrence. PMID- 27195214 TI - Biosensors and their applications - A review. AB - The various types of biosensors such as enzyme-based, tissue-based, immunosensors, DNA biosensors, thermal and piezoelectric biosensors have been deliberated here to highlight their indispensable applications in multitudinous fields. Some of the popular fields implementing the use of biosensors are food industry to keep a check on its quality and safety, to help distinguish between the natural and artificial; in the fermentation industry and in the saccharification process to detect precise glucose concentrations; in metabolic engineering to enable in vivo monitoring of cellular metabolism. Biosensors and their role in medical science including early stage detection of human interleukin-10 causing heart diseases, rapid detection of human papilloma virus, etc. are important aspects. Fluorescent biosensors play a vital role in drug discovery and in cancer. Biosensor applications are prevalent in the plant biology sector to find out the missing links required in metabolic processes. Other applications are involved in defence, clinical sector, and for marine applications. PMID- 27195218 TI - Psychogenic nonepileptic seizures mimicking gelastic seizures: A description of two cases. AB - Psychogenic nonepileptic seizures (PNES) are sudden, involuntary seizure-like attacks that, unlike epileptic seizures, are not related to electrographic ictal discharges and are psychological in nature. Psychogenic nonepileptic seizures presenting symptoms mimic a wide array of nervous system dysfunctions, as they involve changes in behavior, motor activity, sensation, cognitive, and autonomic functions. Spontaneous paroxysms of laughing resembling gelastic seizure have only exceptionally been reported as main symptom of PNES. Here, we describe the cases of two patients with a prolonged history of laughter attacks mistaken for epilepsy and unresponsive to AED treatment. Brain MRI and interictal EEG were unremarkable. Video-EEG monitoring allowed us to document the spontaneous and suggestion-induced habitual episodes that were then diagnosed as PNES. PMID- 27195219 TI - Gelastic epilepsy: Beyond hypothalamic hamartomas. AB - Gelastic epilepsy or laughing seizures have been historically related to children with hypothalamic hamartomas. We report three adult patients who had gelastic epilepsy, defined as the presence of seizures with a prominent laugh component, including brain imaging, surface/invasive electroencephalography, positron emission tomography, and medical/surgical outcomes. None of the patients had hamartoma or other hypothalamic lesion. Two patients were classified as having refractory epilepsy (one had biopsy-proven neurocysticercosis and the other one hippocampal sclerosis and temporal cortical dysplasia). The third patient had no lesion on MRI and had complete control with carbamazepine. Both lesional patients underwent resective surgery, one with complete seizure control and the other one with poor outcome. Although hypothalamic hamartomas should always be ruled out in patients with gelastic epilepsy, laughing seizures can also arise from frontal and temporal lobe foci, which can be surgically removed. In addition, we present the first case of gelastic epilepsy due to neurocysticercosis. PMID- 27195220 TI - Working environment and specialty of choice chosen by the dental students at Prince Sattam Bin Abdulaziz University, Saudi Arabia: A cross-sectional study. AB - OBJECTIVES: This cross-sectional study was conducted to explore the specialty chosen by the dental students for postgraduate studies and the future aspirations of students in a Saudi Arabia dental college. MATERIALS AND METHODS: Of the total number of 120 questionnaires that were distributed, 107 subjects responded with selective responses and a response rate of 89%. A descriptive survey was conducted using one of the questionnaires among the students of dentistry at the dental college, Prince Sattam Bin Abdulaziz University, Al-Kharj among male students (men's college) for a period of 2 months. The data were analyzed using the statistical software program, predictive analytics software Statistics version 22.0 (SPSS Inc., Chicago, IL, USA). RESULTS: A hundred and seven of the 120 students took part in the study. A passion for orthodontics (42.9%) was reported to be the most important factor that influenced the decision to pursue specialty training in orthodontics followed by intellectual stimulation/challenge (25%). The decision to pursue orthodontics was made by 32.1% of the respondents while in dental school; 35.7% took the decision after completing dental school during private practice and 14.3% during a dental residency, whereas 3.6% had already decided before initiating their dental school studies. Working in a private practice environment was preferred by 11 residents (39.3%). Only four residents indicated that they would most likely be practicing in an academic setting while 10 were undecided. CONCLUSIONS: The zest for nonclinical specialties is less among students at Prince Sattam Bin Abdulaziz University's dental college, Saudi Arabia. PMID- 27195221 TI - Comparative failure load values of acrylic resin denture teeth bonded to three different heat cure denture base resins: An in vitro study. AB - AIM AND OBJECTIVES: Acrylic teeth are used for fabrication of dentures. Debonding of tooth - denture base bond is routine problem in dental practice. The aim of this study was to comparatively evaluate failure load of acrylic resin denture teeth bonded to three different heat resin. MATERIALS AND METHODS: Four groups were created out of test samples central incisors (11). Group I: Control, whereas Group II, Group III and Group IV were experimental groups modified with diatoric hole, cingulum ledge lock and Teeth modified with both diatoric hole and cingulum ledge lock, respectively. These test specimens with 3 teeth (2 central [11, 21] and 1, lateral [12] incisors) positioned imitating arrangement of teeth in the conventional denture, prepared by three different heat cure materials (DPI, Trevalon, Acralyn-H). A shear load was applied at cingulum of central incisor (11) at 130 degrees to its long axis using universal tester at a cross head speed of 5 mm/min until failure occurred. Failure load test was conducted and statistical analysis was performed using SPSS 16 software package (IBM Company, New York, U.S). RESULTS: Highest failure load was seen in Group IV specimens, prepared by Trevalon but did not significantly differ from that of DPI. CONCLUSION: The failure load of bonding denture teeth to three different heat cure materials was notably affected by modifications of ridge lap before processing. The specimens with a combination of diatoric hole and cingulum ledge lock, prepared by Trevalon showed highest failure load but did not significantly vary from that of DPI. The control group prepared by Acralyn-H showed lowest failure load but did not significantly differ from that of DPI. PMID- 27195222 TI - Effectiveness of chemomechanical caries removal agents Papacarie((r)) and Carie CareTM in primary molars: An in vitro study. AB - AIMS AND OBJECTIVES: The chemomechanical caries removal system is made presently available containing a natural proteolytic enzyme for ease in the excavation of infected dentin. The aim of the study was to evaluate the efficacy and efficiency of caries removal using Papacarie((r)) and Carie-CareTM. MATERIALS AND METHODS: A total of 30 extracted deciduous molars with proximal caries were collected, and each tooth was sectioned mesiodistally in the center of the carious lesion so that the two halves (buccal and lingual or palatal) have similar carious lesions, thus 30 teeth yielded 60 specimens. The specimens from each tooth were divided alternatively into two groups for caries excavation either using Papacarie((r)) or Carie-CareTM so as to avoid selection bias. Paired t-test was used to compare mean time taken for caries removal and Fischer's exact test was done for comparing bacterial remnants after caries excavation. RESULTS: Mean time taken for caries removal was significantly higher for Carie-CareTM (427.13 s) when compared to Papacarie((r)) (385.8 s). Papacarie((r)) was found to be significantly more efficient in caries removal with marked reduction in the bacterial remnants following excavation. However, both gels were found to be conservative as dentinal tubule destruction was not evident in either of them. CONCLUSION: Both Papacarie((r)) and Carie-CareTM were found to be conservative in caries removal. Papacarie((r)) was more efficient in removing bacteria in lesser time from the infected carious lesion. PMID- 27195223 TI - Assessing Angle's malocclusion among cleft lip and/or palate patients in Jammu. AB - OBJECTIVE: The study was conducted to examine the patients with abnormalities of cleft lip and/or palate and its association with different types of malocclusion. MATERIALS AND METHODS: This descriptive study was done among 168 patients with abnormalities of cleft lip and/or palate. Angle's classification of malocclusion was applied for assessment of occlusion as Class I, Class II, and Class III. The types of oral clefts classification such as cleft lip unilateral and cleft lip bilateral, cleft palate (CP), unilateral cleft lip with palate (UCLP) and bilateral cleft lip with palate (BCLP) was considered. Chi-square test was applied to analyze the data at P < 0.05. RESULTS: The study showed different categories of clefts patients as cleft lip (81), CP (31), and both cleft lip and palate (53). The occurrence of unilateral cleft lip (44) was maximum among the sample followed by UCLP (39), and bilateral cleft lip (31). Maximum subjects with Class II (10.7%) and Class III (4.9%) malocclusion were seen with unilateral cleft lip deformities. None of the patients with UCLP had Class III malocclusion. CONCLUSION: Cleft lip was the most commonly observed deformity and high frequency of Class II and III malocclusion was evident. Therefore, patients with such abnormalities should be screened timely. PMID- 27195224 TI - Assessment of readiness of dental faculty and students in Kuwait to implement a smoking cessation counseling curriculum. AB - AIMS AND OBJECTIVES: The goal of this study was to assess the readiness of both dental faculty and dental students in Kuwait to implement a smoking cessation counseling curriculum. MATERIALS AND METHODS: The study population included all faculty and students in their clinical training years at the Faculty of Dentistry, Kuwait University. The survey instrument was a 42-item questionnaire. Data analysis involved employing various methods of descriptive statistics. RESULTS: Students and faculty reported that their general knowledge of what to include in a cessation message was excellent. Students reported and anticipated more clinical barriers than did the faculty. Both students and faculty agreed strongly that they were willing to refer patients for cessation in their clinical practice, faculty were much less willing to prescribe medications for cessation as compared to students. The majority of students and faculty disagreed with the statement that performing cessation was easy. Responses showed that the use of the 5 A's has not penetrated well into clinical practice for either the students or the faculty. CONCLUSIONS: Clinical students and faculty members believe smoking cessation counseling to be effective; however, their activity was mostly limited to asking patients if they smoked and both reported their knowledge of cessation counseling to be only fair. PMID- 27195225 TI - Prevalence of anterior dental trauma and its associated factors among children aged 3-5 years in Jaipur City, India - A cross sectional study. AB - OBJECTIVE: To study the prevalence of anterior dental trauma and its associated factors among 800 preschool children aged 3 to 5 years in Jaipur City, Rajasthan, India. MATERIALS AND METHODS: A cross-sectional survey was conducted among children aged 3-5 years, who were enrolled in various private and public schools in Jaipur. Parents were asked to fill a form addressing socio-demographic data and clinical examinations were performed by a single dentist. Traumatic dental injuries (TDI) were assessed and recorded based on Andreasen's classification. Associated factors such as sex, socioeconomic status (SES), and the type of injury were also analyzed. The data were analyzed statistically using Statistical Package for the Social Sciences software (version 20). RESULTS: An overall 10.2% prevalence of TDI was observed among the study population. TDI were reported to be more among male children (11.87%) compared to female children (8.14%). Enamel fractures (69%) were the most prevalent type of anterior dental trauma. Upper central incisors were the most frequently affected. The SES of the parents had little influence on the prevalence of TDI. CONCLUSIONS: The prevalence rate of dental trauma among children aged 3-5 years was 10.2%. Associated factors, such as SES, were observed to be not significantly correlated to dental trauma among the studied preschoolers. PMID- 27195226 TI - "Musculoskeletal problem": Its prevalence among Iranian dentists. AB - OBJECTIVES: Musculoskeletal problems (MSPs) are a major complication for practitioners in the field of dentistry. The present study is designed to define the prevalence of MSPs among Iranian dentists. MATERIALS AND METHODS: This was a cross-sectional survey conducted on 600 dentists. The questions were about demographic characteristics, headache, and physical problems of different parts of the body. Data were analyzed using logistic regression analysis. RESULTS: Of all dentists studied, 67.5% had physical problems. These MSPs were observed in neck (51.87%), wrist (92.96%), waist (11.11%), and shoulder (7.40%) of the practitioners. Some practitioners took leave of absence (18.52%), while others (7.40%) underwent medical care. There was a direct correlation between age (P = 0.0001), high body mass index (BMI; P = 0.021), total number of daily under-care patients (P = 0.002), and little physical activity (P = 0.0001) with MSPs. CONCLUSION: The prevalence of MSPs is very high among dentists. Awareness about preventive care is necessary for dentists. The dental curriculum also should address ergonomic issues for dental educators. PMID- 27195227 TI - Evaluation of the efficacy of platelet-rich plasma and platelet-rich fibrin in alveolar defects after removal of impacted bilateral mandibular third molars. AB - AIM AND OBJECTIVES: This study attempted the evaluation of the efficacy of platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) in alveolar defects after removal of bilateral mandibular third molars. MATERIALS AND METHODS: A total of 30 patients reporting to Department of Oral and Maxillofacial Surgery and having bilateral mandibular third molar impaction in both male and female aged between 18 and 30 years were included in this study. PRF and PRP were placed in extraction site and recalled at 2(nd), 4(th), and 6(th) month postoperatively. Data were statistically analyzed using IBM SPSS software for Windows, version 19.0. IBM Corp., Armonk, NY, USA. RESULTS: This study showed decreased probing depth in PRF group compared to PRP and control one. This signifies a better soft tissue healing of extraction sockets with PRF as compared to the PRP and the control group and increase in the bone density highlights the use of PRP and PRF certainly as a valid method in inducing hard tissue regeneration. CONCLUSION: This study indicates a definite improvement in the periodontal health distal to second molar after third molar surgery in cases treated with PRF as compared to the PRP group and control group. Hence, PRP and PRF can be incorporated as an adjunct to promote wound healing and osseous regeneration in mandibular third molar extraction sites. PMID- 27195228 TI - Distribution of smile line, gingival angle and tooth shape among the Saudi Arabian subpopulation and their association with gingival biotype. AB - OBJECTIVES: To determine the occurrence of smile line and maxillary tooth shape in the Saudi Arabian subpopulation, and to estimate the association between these parameters with gingival biotype. MATERIALS AND METHODS: On the fulfillment of selection criteria, total 315 patients belong to Saudi Arabian ethnic group were randomly selected. Two frontal photographs of the patients were acquired. The tooth morphology, gingival angle, and smile line classification were determined with ImageJ image analyzing software. The gingival biotype was assessed by probe transparency method. The obtained data were analyzed with SPSS 19 (IBM Corporation, New York, USA) software to determine the frequency and association between other parameters and gingival biotype. RESULTS: Among the clinical parameters evaluated, the tapering tooth morphology (56.8%), thick gingival biotype (53%), and average smile line (57.5%) was more prevalent. The statistically significant association was found between thick gingival biotype and the square tooth, high smile line. The high gingival angle was associated with thin gingival biotype. CONCLUSIONS: The study results indicate the existence of an association between tooth shape, smile line, and gingival angle with gingival biotype. PMID- 27195229 TI - Prevalence of periodontal diseases among rural population of Mustabad, Krishna District. AB - AIMS AND OBJECTIVES: People in rural areas neglect oral health as they lack awareness on dental diseases and also due to inadequate availability of dental services. The prevalence of illiteracy is also a reason which can be attributed to a poor oral health. This epidemiological study is undertaken to assess the prevalence of periodontal diseases in the rural population of Mustabad - in Krishna, Andhra Pradesh. MATERIALS AND METHODS: A cross-sectional study based on randomized sampling method was carried out using the WHO assessment form (1997) on a population of 470. The data were subjected to statistical analysis using Statistical Package for Social Sciences Version 15.0. RESULTS: The subjects were 220 males and 250 females. Maximum numbers of subjects were in the age group of 35-44 years (21.91%). Prevalence of periodontal disease was found to be 73.62%. The periodontal status deteriorated with aging. Prevalence of periodontitis was higher in females (56.35%) compared to males (43.65%). Males had a higher prevalence of deep pockets (3.18%), whereas females had a higher prevalence of shallow pockets (3.20%). Females had twice the bleeding tendency (18.80%) compared to males (8.64%). CONCLUSION: The increasing prevalence of periodontal diseases is an impending problem which needs immediate intervention, if not it would have a serious negative impact on the future oral health. The need of the hour is more epidemiological studies with a bigger sample are required. PMID- 27195230 TI - Comparison of a commercially available herbal and 0.2% chlorhexidine mouthrinse for prevention of oral malodor: A clinical trial. AB - OBJECTIVES: Despite the adverse effects of chlorhexidine (CHX) in the oral cavity, it is still the most commonly prescribed mouthrinse for halitosis control due to its excellent results. The purpose of this study was to compare the efficacy of a mouthrinse with herbal formulation for halitosis control with 0.2% CHX gluconate containing rinse and to simultaneously assess adverse effects caused by the herbal mouthrinse if any. MATERIALS AND METHODS: Ninety-six systemically healthy subjects with chronic generalized gingivitis were recruited in the study and divided into three groups receiving 0.2% CHX gluconate mouthrinse, herbal mouthrinse, or negative control, respectively as Group A, B, and C. The halimeter scores and organoleptic scores were recorded for each subject at baseline and after scaling. Others parameters recorded were plaque index and gingival index. All scores were reassessed on the 7(th) and 14(th) day, respectively. Statistical analysis was performed using Kruskal-Wallis ANOVA, Mann Whitney U-test, and Wilcoxon matched pairs test. RESULTS: There was an overall reduction in the halimeter scores both in Group A and B subjects which were not statistically significant within the groups; this was in accordance with the decrease in the mean organoleptic scores. Reduction in Group C scores was the least and differed statistically from both Group A and B scores. CONCLUSIONS: The results indicate an equivalent reduction in breath odor by both the herbal mouthrinse and CHX. Furthermore, side effects were less, and patient compliance was more with the herbal mouthrinse, which can thus be prescribed more safely and with predictable outcomes for oral malodor. PMID- 27195231 TI - Comparative evaluation of compressive strength, diametral tensile strength and shear bond strength of GIC type IX, chlorhexidine-incorporated GIC and triclosan incorporated GIC: An in vitro study. AB - AIM: To comparatively evaluate the compressive strength, diametral tensile strength, and shear bond strength of glass ionomer cement type IX, chlorhexidine incorporated glass ionomer cement, and triclosan-incorporated glass ionomer cement. MATERIALS AND METHODS: In this study, glass ionomer cement type IX was used as a control. Chlorhexidine diacetate, and triclosan were added to glass ionomer cement type IX powder, respectively, in order to obtain 0.5, 1.25, and 2.5% concentrations of the respective experimental groups. Compressive strength, diametral tensile strength, and shear bond strength were evaluated after 24 h using Instron Universal Testing Machine. The results obtained were statistically analyzed using the independent t-test, Dunnett test, and Tukey test. RESULTS: There was no statistical difference in the compressive strength, diametral tensile strength, and shear bond strength of glass ionomer cement type IX (control), 0.5% triclosan-glass ionomer cement, and 0.5% chlorhexidine-glass ionomer cement. CONCLUSION: The present study suggests that the compressive strength, diametral tensile strength, and shear bond strength of 0.5% triclosan glass ionomer cement and 0.5% chlorhexidine-glass ionomer cement were similar to those of the glass ionomer cement type IX, discernibly signifying that these can be considered as viable options for use in pediatric dentistry with the additional value of antimicrobial property along with physical properties within the higher acceptable range. PMID- 27195232 TI - Effect of hyperbaric oxygen profiles on the bond strength of repaired composite resin. AB - OBJECTIVE: This study was performed to evaluate the bond strength of repaired three types of composite resins under various hyperbaric oxygen (HBO) profiles with various session numbers. MATERIALS AND METHODS: Sixty specimens of three types of composite resin (nanofilled composite, nanohybrid composite and microfilled composite) each type of composite was divided into four group according to various profiles of HBO treatment (control, 2bar, 3 bar and 5 bar). Then, the specimens were repaired; thermocycled, the tensile bond strength were measured. Then the data were analyzed by One-way ANOVA followed by Tukey's post hoc test (alpha = 0.05). RESULTS: The highest bond strength was obtained for the repaired nanofilled composite resin specimens while; the lowest bond strength was obtained for the repaired microfilled composite resin specimens. The highest tensile bond strength was recorded for the specimens who treated with the highest pressure of HBO. CONCLUSION: The bond strength of repaired nanofilled composite resins is better than the other types of composite resin. The highest pressure of HBO, the highest bond strength of repaired composite resins. PMID- 27195233 TI - Detection and management of a complex canal configuration in mesiobuccal root of maxillary first molar using three dimensional imaging. AB - This case report discusses the identification and management of complex canal configuration of 3-2-1 in the mesiobuccal (MB) root of the maxillary left first molar. Careful attention to details of the pulpal floor and applying the knowledge of the laws of orifice location along with deepening the subpulpal groove with ultrasonic tips helped in identifying the three MB canals. Manual scouting helped in understanding the anatomic configuration; the use of three dimensional imaging technique and spiral computed tomography (SCT) confirmed the same. SCT images showed buccolingually wide and bulbous mesiobuccal root with three separate canals at coronal third that merged into two canals in the middle and exited as a single canal at the apex. This article highlights the role of SCT in three-dimensionally analyzing the unseen rarest canal configurations that ultimately enabled the clinician to thoroughly explore, debride, and obturate the entire root canal system. PMID- 27195234 TI - Early prevention and intervention of Class II division 1 in growing patients. AB - Early screening and diagnosis help in preventing and intercepting the severity of the malocclusion which helps in addressing the esthetic and functional concerns. Growth modulation such as mandibular advancement has been an effective procedure in orthodontics. Mandibular growth advancer (MGA) and PowerScope are gaining popularity recently as these are effective in achieving the mandibular advancement and ease of fabrication, placement, and wear. MGA was fabricated by making the upper and lower splints separately and are placed in the oral cavity by joining the two splints in the new construction bite using cold cure, MGA when worn during growth phase helps in condylar remodeling in the temporomandibular joint thus helps in advancement of the mandible. The proclination of the upper anteriors in Class II division 1 can be moved lingually by activating the labial bow in the splint. Dr. Andy Hayes worked in conjunction with American orthodontics developed PowerScope. PowerScope delivers Class II correction with a combination of patient comfort and ease of use that was unmatched among other appliances. This ready to use chairside solution required no laboratory setup, making for a much quicker, and easier installation process and appointment. PowerScopes high quality, fixed one-piece design requires no patient compliance. These superior qualities of PowerScope help in correction of Class II skeletal growing patient in conjunction with fixed orthodontic therapy. MGA and PowerScope were chosen as a functional appliance for this study, which shows decreased ANB angle and effective mandible length was increased. PMID- 27195235 TI - Arterial Stiffness Gradient. AB - BACKGROUND: Aortic stiffness is a strong predictor of cardiovascular mortality in various clinical conditions. The aim of this review is to focus on the arterial stiffness gradient, to discuss the integrated role of medium-sized muscular conduit arteries in the regulation of pulsatile pressure and organ perfusion and to provide a rationale for integrating their mechanical properties into risk prediction. SUMMARY: The physiological arterial stiffness gradient results from a higher degree of vascular stiffness as the distance from the heart increases, creating multiple reflective sites and attenuating the pulsatile nature of the forward pressure wave along the arterial tree down to the microcirculation. The stiffness gradient hypothesis simultaneously explains its physiological beneficial effects from both cardiac and peripheral microcirculatory points of view. The loss or reversal of stiffness gradient leads to the transmission of a highly pulsatile pressure wave into the microcirculation. This suggests that a higher degree of stiffness of medium-sized conduit arteries may play a role in protecting the microcirculation from a highly pulsatile forward pressure wave. Using the ratio of carotid-femoral pulse wave velocity (PWV) to carotid-radial PWV, referred to as PWV ratio, a recent study in a dialysis cohort has shown that the PWV ratio is a better predictor of mortality than the classical carotid femoral PWV. KEY MESSAGES: Theoretically, the use of the PWV ratio seems more logical for risk determination than aortic stiffness as it provides a better estimation of the loss of stiffness gradient, which is the unifying hypothesis that explains the impact of aortic stiffness both on the myocardium and on peripheral organs. PMID- 27195236 TI - Aortic Root Calcification: A Possible Imaging Biomarker of Coronary Atherosclerosis. AB - It has been reported that coronary atherosclerosis risk assessment using coronary artery calcium and thoracic aorta calcium quantification may improve risk stratification as it can lead to the reclassification of persons at increased risk. The aortic root has been characterized by its close anatomical proximity to the ostial origins of the right and left coronary arteries, and it can be evaluated using multi-detector computed tomography without additional radiation exposure and the use of contrast. The correlations between aortic root calcification and coronary atherosclerotic markers as well as cardiac risk factors have been analyzed. PMID- 27195237 TI - Determinants and Prognostic Significance of the Renal Resistive Index. AB - BACKGROUND: The noninvasive assessment of renal hemodynamics is currently possible by assessing the renal resistive index (RRI) derived from intrarenal Doppler arterial waveforms as (peak systolic velocity - end-diastolic velocity)/peak systolic velocity. In this review, we outline the important determinants of the RRI to clarify the true identity of the RRI and highlight its potential diagnostic and prognostic value in renal and cardiovascular pathology. SUMMARY: Although the RRI was initially considered to reflect intrarenal vascular pathological processes, this index is actually a product of a complex interaction between renal and systemic vascular wall properties and hemodynamic factors. Indeed, studies in patients and general populations consistently demonstrated a significant and direct association between the RRI and central or peripheral pulse pressure independent of other covariables. Moreover, studies in renal transplant patients also showed that the RRI mainly reflects characteristics of the recipient but not those of the graft. Thus, the major influence of the systemic hemodynamics on the intrarenal arterial waveforms excludes RRI as a specific marker of renal vascular pathology. On the other hand, because the RRI reflects pulsatility in renal arteries, it might be useful for the early detection of renal microvascular damage. Future longitudinal studies are still needed to clarify whether the detection of Doppler changes in intrarenal arteries might yield an improvement in the adverse cardiovascular and renal outcome. CONCLUSION: Published studies on RRI imply that the interaction between the systemic hemodynamics and peripheral circulation in the kidney is a complex physiological phenomenon. In addition to renal vascular properties, the central hemodynamic factors significantly influence the intrarenal arterial Doppler waveform patterns. Previous research also suggested an important role of the RRI for the evaluation of renal target organ damage, particularly in patients with increased pulsatility of the intrarenal blood flow. PMID- 27195238 TI - Comment on the Paper by Cauwenberghs and Kuznetsova Entitled 'Determinants and Prognostic Significance of the Renal Resistive Index'. PMID- 27195239 TI - Cerebral Small Vessel Disease and Arterial Stiffness: Tsunami Effect in the Brain? AB - BACKGROUND: Cerebral small vessel diseases, including silent lacunar infarcts, white matter hyperintensities, and microbleeds, pose a risk for cerebrovascular disease, cognitive impairment, and the geriatric syndrome via effects on arterial stiffness. However, the vascular, physiological, and metabolic roles of arterial stiffness in cerebral small vessel diseases remain unclear. SUMMARY: Arterial stiffness can be assessed using various indicators such as the ankle-brachial index, pulse wave velocity, cardio-ankle vascular index, and augmentation index. Arterial stiffness is independently associated with all components of cerebral small vessel disease including silent lacunar infarcts, white matter hyperintensities, and microbleeds, although there are some methodological differences between the various surrogate markers. Evidence of arterial stiffness indicates microvessel arteriosclerosis presenting with vascular endothelial dysfunction. Further, vascular narrowing due to atherosclerosis and vascular stiffness due to lipohyalinosis can accelerate the pulse waves. This hemodynamic stress, pulsatile pressure, or blood pressure variability can cause a 'tsunami effect' towards the cerebral parenchyma and lead to cerebral small vessel disease. Previous studies have shown that silent lacunar infarcts and white matter hyperintensities are strongly associated with arterial stiffness. However, the association between microbleeds and arterial stiffness remains controversial, as there are two vessel mechanisms related to microbleeds: cerebral amyloid angiopathy and hypertensive small vessel disease. KEY MESSAGES: Cerebral small vessel disease with associated arterial stiffness is a risk factor for silent cerebral lesions, stroke, and cognitive impairment. Improvement of the living environment, management of risk factors, and innovation and development of novel drugs that improve arterial stiffness may suppress the progression of cerebral small vessel disease, and may reduce the risk for stroke and dementia. PMID- 27195240 TI - New Insight into Effects of beta-Blockers on Arterial Functions. AB - The effects of beta-blockers on arterial properties are not well investigated. In our recent study, we compared the effects of the two beta-blockers celiprolol and bisoprolol on blood pressure, baroreflex sensitivity (BRS), flow-mediated vasodilatation, and vascular stiffness. We found that bisoprolol achieved a greater reduction in the pulse rate and improved BRS and vascular stiffness, whereas celiprolol reduced the central blood pressure level. In this review, the mechanisms of different types of beta-blockers and their effects on arteries are discussed, and the appropriate use of beta-blockers in hypertensive subjects will be proposed. PMID- 27195241 TI - Brachial-Ankle Pulse Wave Velocity: Background, Method, and Clinical Evidence. AB - BACKGROUND: The populations of many developed countries are becoming progressively older. In aged societies, assessment of total vascular risk is critically important, because old age is usually associated with multiple risks. In this regard, pulse wave velocity (PWV) could be a global cardiovascular marker, since it increases with advancing age, high blood pressure, hyperglycaemia, and other traditional risks, summating cardiovascular risks. Carotid-femoral PWV has been widely applied in Western countries and has been used as a gold-standard PWV measure. However, this measure has never been implemented by general practitioners in Japan, possibly because of methodological difficulties. The life expectancy of Japanese people is now the highest in the world, and the establishment of an adequate total vascular risk measure is an urgent need. Against this background, brachial-ankle PWV was developed at the beginning of this century. SUMMARY: Measurement of this parameter is easy, and its reproducibility is good. Moreover, the generality of the methodology is guaranteed. Brachial-ankle PWV has been reported to consistently increase with most traditional cardiovascular risk factors except dyslipidaemia. A meta analysis of cohort studies including various levels of risk has shown that a 1 m/s increase in brachial-ankle PWV is associated with a 12% increase in the risk of cardiovascular events. Moreover, simultaneous evaluation of the ankle-brachial index could allow further risk stratification of high-risk individuals, who are common in aged societies. This unique feature is indispensable for the management of aged populations, who usually are exposed to multiple risks and have polyvascular diseases. This evidence, however, is chiefly derived from East Asian countries. The collection of data from Caucasian populations, therefore, remains a task for the future. KEY MESSAGE: Brachial-ankle PWV has the potential to become a measure of arterial stiffness worldwide. PMID- 27195242 TI - Practical Suitability of a Stand-Alone Oscillometric Central Blood Pressure Monitor: A Review of the Microlife WatchBP Office Central. AB - Accumulating evidence indicates that central blood pressure (CBP) is a better cardiovascular risk predictor than brachial blood pressure (BP). Although more additional benefits of CBP-based treatment above usual hypertension treatment are to be demonstrated, the demand for implementing CBP assessment in general clinical practice is increasing. For this, the measurement procedure must be noninvasive, easy to perform, and cost- and time-efficient. Therefore, oscillometric devices with the possibility to assess CBP seem the best option. Recently, such an oscillometric BP monitor, the Microlife WatchBP Office Central, was developed, which demonstrated its high accuracy in a validation study against invasive BP measurement. Calibration errors of this device are limited because the procedure is automated, standardized, and performed at the same place of and within 30 s from pulse wave assessment. The transformation from the peripheral pulse wave to CBP is done by means of an individual-based pulse wave analysis according to a theory of arterial compliance and wave reflections. In addition, the device has demonstrated to enable a more reliable diagnosis of hypertension by CBP than by peripheral BP, with a lower frequency of over- and underdiagnosis. Altogether, the available clinical evidence suggests that the Microlife WatchBP Office Central fulfills the criteria for general clinical use. PMID- 27195243 TI - Association between Tumor Necrosis Factor-alpha (-238G/A and -308G/A) Gene Polymorphisms and Risk of Ischemic Stroke: A Meta-Analysis. AB - Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory pleiotropic cytokine which may contribute to the initiation and progression of ischemic stroke (IS). Thus far, numerous studies have been performed to examine the association between -238G/A (rs361525) and -308G/A (rs1800629) polymorphisms in the promoter regions of the TNF-alpha gene and susceptibility to IS, but results are still conflicting. The aim of this meta-analysis is to provide a relatively comprehensive account of the association between TNF-alpha -238G/A and -308G/A gene polymorphisms and susceptibility to IS. A literature search for eligible candidate gene studies published before April 20, 2015, was conducted in the PubMed, Medline, EMBASE and Google Scholar databases. The following combinations of main keywords were used: ('Tumor Necrosis Factor-Alpha' or 'TNF-alpha') and ('ischemic stroke' or 'cerebral infarction' or 'IS') and ('genetic polymorphism' or 'single nucleotide polymorphisms' or 'SNP'). Fixed- or random-effect models were used to estimate the pooled odds ratio (OR) and 95% confidence interval (CI). Meta-analysis was carried out by using RevMan 5.3 software. For TNF-alpha 238G/A gene polymorphism, 7 case-control studies with a total of 1,846 IS patients and 1,905 controls showed a significant association with susceptibility to IS under a dominant model (AA + GA vs. GG; OR, 1.40; 95% CI, 1.11-1.76; p value 0.004). For TNF-alpha -308G/A gene polymorphism, 16 case-control studies with a total of 5,651 IS patients and 5,792 controls showed a significant protective association with susceptibility to IS under a dominant model (AA + GA vs. GG; OR, 0.78, 95% CI, 0.63-0.97; p value 0.03). Our meta-analysis shows that TNF-alpha -238G/A gene polymorphism is more likely to be associated with the risk of IS in Caucasian populations as compared to Asian populations. However, TNF alpha -308G/A gene polymorphism is more likely to be protective against IS in Asian populations as compared to Caucasian populations. Further large, well designed prospective epidemiological studies are needed to confirm these findings. PMID- 27195244 TI - Arterial Stiffness and Chronic Kidney Disease. AB - Chronic kidney disease (CKD) is a major public health concern due to the high prevalence of associated cardiovascular (CV) disease. CV mortality is 10-30 times higher in end-stage renal disease patients than in the age-adjusted general population. The last 20 years have been marked by a huge effort in the characterization of the vascular remodeling process associated with CKD and its consequences on the renal, CV and general prognosis. By comparison with patients with normal renal function, with or without hypertension, an increase in large artery stiffness has been described in end-stage renal disease as well as in CKD stages 2-5. Most clinical studies are consistent with the observation that damage to large arteries may contribute to the high incidence of CV disease. By contrast, the impact of large artery stiffening and remodeling on CKD progression is still a matter of debate. Concomitant exposure to other CV risk factors, including diabetes, seems to play a major role in the association between aortic stiffness and estimated GFR. The conflicting results obtained from longitudinal studies designed to evaluate the impact of baseline aortic stiffness on GFR progression are detailed in the present review. Only pulse pressure, central and peripheral, is almost constantly associated with incident CKD and GFR decline. Kidney transplantation improves patients' CV prognosis, but its impact on arterial stiffness is still controversial. Donor age, living kidney donation and mean blood pressure appear to be the main determinants of improvement in aortic stiffness after kidney transplantation. PMID- 27195245 TI - Hyperuricemia, Cardiovascular Disease, and Hypertension. AB - In recent years, there has been an increase in the prevalence of hyperuricemia, and the latter has attracted attention as an adult lifestyle-associated disease, together with hypertension, diabetes, and dyslipidemia. Although hyperuricemia is known to be an independent risk factor for hypertension, whether it is an independent risk factor for cardiovascular disease remains controversial. Recently, some small-scale interventional studies on antihyperuricemic medications showed that the latter improved angina symptoms and prevented cardiovascular disease. Here, we will mainly explain the cause of hyperuricemia and the associations between hyperuricemia, hypertension, and cardiovascular disease based on the latest published evidence. PMID- 27195247 TI - Comparing the Spiritual Health and Quality of Life in Addicted and Non-Addicted Patients in the City of Birjand, Iran. AB - BACKGROUND: Substance abuse is a chronic phenomenon that affects many physical, psychological, social, familial and economic elements. Abusers are left with severely reduced interaction both with other individuals and society. OBJECTIVES: The aim of this study was to compare the spiritual health of addicts and people with a normal quality of life in the city of Birjand, Iran. PATIENTS AND METHODS: The sample consisted of 100 non-addicted subjects and 100 patients who were drug addicts in treatment centers and rehabilitation facilities both public and private in Birjand. Normal sampling measures were used to find subjects of the same age and gender. The subjects completed a spiritual health questionnaire and the short form of the world health organization's (WHO) Quality of life questionnaire, and the data were analyzed using multivariate ANOVA. RESULTS: The results of ANOVA showed significant differences between addicted and non addicted individual on spiritual well-being subscales. CONCLUSIONS: The strengthening of spiritual and religious attitudes among drug users encourages them to engage in and justify actions that are relevant to their health. When this happens, their quality of life increases significantly. PMID- 27195246 TI - Quantification of the Interrelationship between Brachial-Ankle and Carotid Femoral Pulse Wave Velocity in a Workplace Population. AB - BACKGROUND: Brachial-ankle pulse wave velocity (PWV) is increasingly used for the measurement of arterial stiffness. In the present study, we quantified the interrelationship between brachial-ankle and carotid-femoral PWV in a workplace population, and investigated the associations with cardiovascular risk factors and carotid intima-media thickness (IMT). METHODS: Brachial-ankle and carotid femoral PWV were measured using the Omron-Colin VP1000 and SphygmoCor devices, respectively. We investigated the interrelationship by the Pearson's correlation analysis and Bland-Altman plot, and performed sensitivity and specificity analyses. RESULTS: The 954 participants (mean +/- standard deviation age 42.6 +/- 14.2 years) included 630 (66.0%) men and 203 (21.3%) hypertensive patients. Brachial-ankle (13.4 +/- 2.7 m/s) and carotid-femoral PWV (7.3 +/- 1.6 m/s) were significantly correlated in all subjects (r = 0.75) as well as in men (r = 0.72) and women (r = 0.80) separately. For arterial stiffness defined as a carotid femoral PWV of 10 m/s or higher, the sensitivity and specificity of brachial ankle PWV of 16.7 m/s or higher were 72 and 94%, respectively. The area under the receiver operating characteristic curve was 0.953. In multiple stepwise regression, brachial-ankle and carotid-femoral PWV were significantly (p < 0.001) associated with age (partial r = 0.33 and 0.34, respectively) and systolic blood pressure (partial r = 0.71 and 0.66, respectively). In addition, brachial-ankle and carotid-femoral PWV were significantly (p < 0.001) associated with carotid IMT (r = 0.57 and 0.55, respectively) in unadjusted analysis, but not in analysis adjusted for cardiovascular risk factors (p >= 0.08). CONCLUSIONS: Brachial-ankle and carotid-femoral PWV were closely correlated, and had similar determinants. Brachial-ankle PWV can behave as an ease-of-use alternative measure of arterial stiffness for assessing cardiovascular risk. PMID- 27195248 TI - Co-occurrence of multiple sclerosis and Parkinson disease. AB - Parkinson disease (PD) is a neurodegenerative disease of the central nervous system (CNS) with the highest prevalence in adults over 60 years of age On the other hand multiple sclerosis (MS), which mostly affects individuals between 20 and 40 years of age, is another neurodegenerative and autoimmune disease of the CNS, however, less common than PD. Here we aim to report the case of a 39-year old woman, who developed PD 18 years after diagnosis of MS. PMID- 27195249 TI - Dietary fat intake and functional dyspepsia. AB - A few studies have assessed the effects of fat intake in the induction of dyspeptic symptoms. So, the aim of this study was to review the articles regarding the dietary fat intake and FD. We used electronic database of PubMed to search. These key words were chosen: FD, dietary fat, dyspeptic symptom, energy intake and nutrients. First, articles that their title and abstract were related to the mentioned subject were gathered. Then, full texts of related articles were selected for reading. Finally, by excluding four articles that was irrelevant to subject, 19 relevant English papers by designing clinical trial, cross-sectional, case-control, prospective cohort, and review that published from 1992 to 2012 were investigated. Anecdotally, specific food items or food groups, particularly fatty foods have been related to dyspepsia. Laboratory studies have shown that the addition of fat to a meal resulted in more symptoms of fullness, bloating, and nausea in dyspeptic patients. Studies have reported that hypersensitivity of the stomach to postprandial distension is an essential factor in the generation of dyspeptic symptoms. Small intestinal infusions of nutrients, particularly fat, exacerbate this hypersensitivity. Moreover, evidence showed that perception of gastric distension increased by lipids but not by glucose. Long chain triglycerides appear to be more potent than medium chain triglycerides in inducing symptoms of fullness, nausea, and suppression of hunger. Thus, Fatty foods may exacerbate dyspeptic symptoms. Therefore, it seems that a reduction in intake of fatty foods may useful, although this requires more evaluations. PMID- 27195250 TI - Primary ectopic frontotemporal extradural craniopharyngioma. AB - We present a case of primary ectopic frontotemporal extradural craniopharyngioma. Primary ectopic craniopharyngiomas are very rare and have been reported involving the fourth ventricle, infrasellar region, lateral ventricle, temporal area, cerebellopontine angle, clivus, corpus callosum, and prepontine cistern. There was just 1 case of craniopharyngioma previously presented in the literature, with nearly same location as the presenting case. PMID- 27195252 TI - Evaluation of the effect of Pulicaria gnaphalodes and Perovskia abrotanoides essential oil extracts against Mycobacterium tuberculosis strains. AB - BACKGROUND: Mycobacterium tuberculosis (MTB) is the causative agent of tuberculosis (TB), which remains one of the major public health problems in the world. The increasing incidence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) worldwide highlights the urgent need to search for alternative antimycobacterial agents. More and more people in developing countries utilize traditional medicine for their major primary health care needs. It has been determined that the medicinal plants Pulicaria gnaphalodes and Perovskia abrotanoides possess strong antibacterial effect. MATERIALS AND METHODS: In this study, the antimycobacterial effects of P. gnaphalodes and P. abrotanoides essential oil on MTB were examined. Essential oil was prepared from P. gnaphalodes aerial parts and P. abrotanoides flower. The effects of six different concentrations (20 MUg/ml, 40 MUg/ml, 80 MUg/ml, 160 MUg/ml, 320 MUg/ml, and 640 MUg/ml) were examined against sensitive isolates of MTB and MTB H37Rv (ATCC 27294). RESULTS: The results showed that P. gnaphalodes and P. abrotanoides essential oil extracts have strong inhibitory effects on MTB. This activity for P. gnaphalodes was observed from very low (4%) to good (70.9%) effect; meanwhile, this activity for P. abrotanoides was observed from very low (4%) to strong (86%) effect. CONCLUSION: The mean of inhibition percentage for P. gnaphalodes and P. abrotanoides in 640 MUg/ml was 58.1% and 76.2%, respectively. So, P. abrotanoides plant is more effective against MTB than P. gnaphalodes. Identification of the effective fraction against MTB is a further step to be studied. PMID- 27195251 TI - Interaction of central Angiotensin II and estrogen on systolic blood pressure in female DOCA-salt treated rats. AB - BACKGROUND: There is a probable interaction of central angiotensin II (Ang II) and estrogen (Est) on blood pressure in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Therefore, in the present study, the interaction between Ang II and Est in ovariectomized (Ovx) and Sham rats that were treated with DOCA- salt was evaluated. MATERIALS AND METHODS: The female rats were divided into 10 groups as follows: Sham, Ovx, Sham-DOCA, Ovx-DOCA, Sham-DOCA-estrogen (E), Ovx DOCA-E, Sham-DOCA-losartan (L), Ovx-DOCA-L, Sham-DOCA-L-E, and Ovx-DOCA-L-E. The Est groups received estradiol valerate (2 mg/kg; daily; subcutaneously (s.c)) for four weeks. Following that, several doses of Ang II (0.5, 5, 50, 500, 5000 ng/5 MUl) were injected via the intracerebroventricular (i.c.v) route and the changes in systolic blood pressure (SBP) were evaluated. In the losartan groups, 200 MUg losartan was injected (i.c.v) 15 minutes after the Ang II injection and the blood pressure was recorded. Treatment by DOCA was performed by removal of one kidney, injection of DOCA (45 mg/kg i.p), and adding of sodium chloride (NaCl) (1%) and potassium chloride (KCl) (0.1%) in the drinking water. RESULTS: The SBP was increased by Ang II and this effect in DOCA-salt treated rat was higher than in the untreated groups. The effect of Ang II on SBP in groups that were treated with Est and L was lower than that in the DOCA-salt groups. Increase in SBP was strongly attenuated by Ang II in groups that were co-treated with both Est and L compared to the DOCA-treated rats. These results showed that Est significantly attenuated the effect of central Ang II on SBP in the DOCA-salt treated rats. CONCLUSION: We suggest that there are interactions between E and Ang II in the control of blood pressure in DOCA-salt treated rats. PMID- 27195253 TI - Serum, saliva, and GCF concentration of RANKL and osteoprotegerin in smokers versus nonsmokers with chronic periodontitis. AB - BACKGROUND: The role of host response in periodontitis pathogenesis is confirmed, and it is well established that immune response plays a major role in the alveolar bone destruction. In the investigation of these responses, the role of receptor activator of the nuclear factor-kB ligand (RANKL)-osteoprotegerin (OPG) system is the most promising. Smoking can affect the RANKL-OPG system in a manner that will further enhance bone loss in periodontitis. The aim of this study is to assess the serum, saliva, and gingival crevicular fluid (GCF) concentration of RANKL and OPG in smoker versus nonsmoker untreated chronic periodontitis (CP) patients. MATERIALS AND METHODS: Thirty-nine subjects were included in the present cross-sectional study: 29 systemically healthy CP male patients (15 smokers, 14 nonsmokers) and 10 systemically and periodontally healthy nonsmoker male subjects. Serum, GCF, and whole saliva samples were obtained from the subjects. The enzyme-linked immunosorbent assay (ELISA) kits were used for assaying the concentrations of RANKL and OPG in the samples. The one-way analysis of variance (ANOVA) test and the least significant difference (LSD) post hoc test were utilized to compare differences between the groups. RESULTS: RANKL and OPG concentrations in saliva, serum, and GCF did not show any significant difference among all groups (P > 0.05). Salivary RANKL/OPG ratios were significantly higher in the nonsmoker CP group than in the healthy control group (P > 0.05) but they were not statistically significant among smoker periodontitis patients. CONCLUSIONS: The salivary RANKL/OPG ratio was higher in nonsmokers with periodontitis in comparison with smoker periodontitis patients. PMID- 27195254 TI - Clinical Concerns about Recurrence of Non-Functioning Pituitary Adenoma. AB - BACKGROUND: Non-functioning pituitary adenomas (NFPA) are clinically challenging because they present at a late stage with local mass effects or hypopituitarism. Surgery for non-functioning pituitary adenoma requires a special strategic approach for both minimal morbidity and radical resection. However, the clinical predictive factors associated with recurrence are limited. Here, we investigated optimal treatment of non-functioning pituitary adenoma. METHODS: We enrolled 289 patients who presented with non-functioning pituitary adenoma between January 2000 and January 2012 and who had received follow-up for at least one year for this retrospective study. Of these patients, 152 were male and 137 were female, with a median age of 51 years (range 15.79 years) and a median follow-up of four years (range 1.12.6 years). Characteristics of patients and tumors were reviewed with electronic medical records and radiologic images, retrospectively. RESULTS: Of the tumors, 193 were gross-totally resected, 53 were near-totally resected, and 43 were sub-totally resected. The extent of resection and adjuvant radiotherapy were both statistically significant prognostic factors of recurrence. Immunohistochemistry of tumor specimens did not yield consistent results. CONCLUSION: With a high rate of recurrence, NFPA should be closely followed-up over a long-term period. Improvement of surgical techniques with advanced surgical equipment and adjuvant radiosurgery would lead to reduce the recurrence rate and improve patients' outcome. PMID- 27195255 TI - Hemangiopericytoma of the Cerebellopontine Angle: A Wolf in Sheep's Clothing. AB - Primary meningeal hemangiopericytoma (HPC) is a rare, aggressive dura based tumor that remarkably mimics a meningioma clinically and radiologically. Its occurrence within the cerebellopontine angle (CPA) is exceptional, and establishing the exact diagnosis is of the utmost importance since total resection remains the cornerstone of treatment. A 42-year-old man presented with a three-month history of progressively worsening vertigo and difficulty in walking. On admission, his neurological examination revealed a right peripheral facial palsy, right abducens palsy and left hemiparesis, suggesting the diagnosis of Millard-Gubler syndrome. Computed tomography and magnetic resonance imaging demonstrated a homogeneously enhancing dura based lesion of the right CPA causing major brain stem compression. There was no widening of the ipsilateral internal auditory canal. A standard retrosigmoid craniotomy was performed to access the right CPA. Exposure of the lesion revealed a well-encapsulated, gray, fibrous lesion, which appeared to originate from the tentorium. Gross total resection was achieved and confirmed radiologically. The microscopic features and the immunohistochemical profile confirmed the diagnosis of a HPC, and adjuvant radiation therapy was administered. Ten years later, the patient presented with a severe neurological deficit due to a local recurrence, but at that time refused any second intervention. He died three months later. HPC can locate within the CPA and present as a Millard-Gubler syndrome. The diagnosis should be kept in mind in case of a CPA dura based tumor. Radical surgery plus radiation therapy can maximize the recurrence-free survival and close follow-up remains mandatory to spot recurrences early. PMID- 27195256 TI - Recurrent Giant Cell Tumor of Skull Combined with Multiple Aneurysms. AB - Giant cell tumors are benign but locally invasive and frequently recur. Giant cell tumors of the skull are extremely rare. A patient underwent a surgery to remove a tumor, but the tumor recurred. Additionally, the patient developed multiple aneurysms. The patient underwent total tumor resection and trapping for the aneurysms, followed by radiotherapy. We report this rare case and suggest some possibilities for treating tumor growth combined with aneurysm development. PMID- 27195257 TI - Cellular Neurothekeoma of the Scalp in the Elderly. AB - Cellular neurothekeoma (CNT) is an uncommon variant of neurothekeoma that is composed of pithelioid to spindled cells with variable nuclear atypia or pleomorphism but no myxoid stroma. CNT occurs predominantly in the head and neck or upper trunk of children and young adults, with female predominance. The following case is different from typical CNTs. An 88-year-old female presented with a palpable mass on the scalp, which we excised. Histologically, the tumor was non-encapsulated and composed of spindled and epithelioid cells arranged in fascicles and nodules separated by a collagen-rich stroma. Immunohistochemical analysis showed that the epithelioid and spindle-shaped cells were focally positive for vimentin, neuron-specific enolase, smooth muscle actin, CD68, and CD10 but negative for S-100 protein, HMB-45, epithelial membrane antigen, and CD34. We report a new case of CNT that arose in the scalp of an older patient and that was associated with uncommon clinical, histological, and immunohistochemical profiles. PMID- 27195258 TI - A Case of Nongerminomatous Germ Cell Tumor with Fulminant Course Concomitant Leptomeningeal Metastasis. AB - We present the case of a 9-year-old boy with a non-germinomatous germ cell tumor (NGGCT) in the pineal gland that exhibited a fulminant course following chemo- and radiotherapy. After the detection of the tiny cerebellar enhancing nodule at the end of chemo- and radiotherapy, tumor seeding progressed rapidly into the entire cisternal space. We herein report a rare case of NGGCT with fulminant clinical course of concomitant cerebellar seeding, with review of literature. PMID- 27195260 TI - Acute Paraplegia as a Result of Hemorrhagic Spinal Ependymoma Masked by Spinal Anesthesia: Case Report and Review of Literature. AB - Ependymomas are the most common intramedullary spinal cord tumors in adults. Although a hemorrhage within spinal ependymoma on imaging studies is not uncommon, it has rarely been reported to bea cause of acute neurological deficit. In the present report, we describe a case of a 24-year-old female patient who developed acute paraplegia as a result of hemorrhagic spinal ependymoma immediately after a cesarean delivery under spinal regional anesthesia. We review the literature of hemorrhagic spinal ependymomas presenting with acute neurological deficit and discuss the most appropriate treatment for a good neurological recovery. PMID- 27195259 TI - A Case of Langerhans Cell Histiocytosis Manifested as a Suprasellar Mass. AB - Langerhans cell histiocytosis (LCH) has diverse clinical manifestations, including intracranial mass lesions. We report a case of LCH that manifested as a suprasellar mass, and initially misdiagnosed as a germ cell tumor. A 29-year-old woman presented with polyuria, polydipsia and amenorrhea. Laboratory findings revealed hypopituitarism with central diabetes insipidus, and a suprasellar mass and a pineal mass were observed on magnetic resonance imaging. Under the clinical impression of a germ cell tumor, the patient was treated with germ cell tumor chemotherapy (cisplatin and etoposide) and radiation therapy without biopsy. After initial shrinkage of the lesions, further growth of the tumor was observed and a biopsy was performed. The histopathology revealed LCH. After chemotherapy according to the LCH III protocol, the tumor disappeared. She is on regular follow up for 5 years without relapse. The present findings indicate that LCH should be included in the differential diagnosis of a suprasellar mass, even in adults, especially when it manifests with diabetes insipidus. This case also underscores the importance of a histopathologic diagnosis in patients with suprasellar tumors before the initiation of a specific therapy, even if the clinical findings are highly suggestive of a specific diagnosis. PMID- 27195261 TI - Hypothalamic Extraventricular Neurocytoma (EVN) in a Pediatric Patient: A Case of EVN Treated with Subtotal Removal Followed by Adjuvant Radiotherapy. AB - Extra ventricular neurocytoma (EVN) is a rare brain tumor with histologic features similar with a central neurocytoma, but located outside of the ventricular system. In this study, we present an unusual case of hypothalamic EVN in a 14-year-old patient. The patient underwent subtotal removal and had tumor relapse. The patient was then treated using intensity modulated radiation therapy, and the tumor remained stable for 24 months. This case report may be important in that this is the first pediatric case of EVN located in the hypothalamic region. EVN has similar radiologic features with pilocytic astrocytomas and therefore a hypothalamic EVN may be misdiagnosed as a hypothalamic glioma. Also, the pathologic-radiologic-clinical correlation of EVN located in the hypothalamic area may be different from that of EVNs originating from other usual sites. PMID- 27195262 TI - Clinical, Radiologic, and Pathologic Findings of Subdural Osteoma: A Case Report. AB - We present a case of a subdural osteoma. A 29-year-old female presented with a 3 year history of headaches. Computed tomography scan revealed a homogeneous high density lesion isolated from the inner table of the frontal bone (a lucent dural line) in the right frontal convexity. Magnetic resonance imaging revealed an extra-axial lesion with a broad base without dural tail sign and punctate enhancement pattern characteristic of abundant adipose tissue. Upon surgical excision, we found a hard bony mass clearly demarcated from the dura. The mass displayed characteristics of an osteoma upon histological examination. The symptom was relieved after operation. PMID- 27195263 TI - Large Mature Cystic Teratoma of the Third Ventricle in Infancy: A Case Report and Review of Literatures. AB - Teratomas of the central nervous system are rare and are frequently found in children and young adults. Cystic teratomas found in infancy is a well-recognized but infrequent entity. Intracranial teratomas,like teratomas in general, tend to arise from midline structures such as the pineal gland, but has rarely been found in the third ventricle. We report a rare case of a 6-month-old infant with a mature cystic teratoma of the third ventricle with a review of literatures. PMID- 27195264 TI - Oral Malignant Melanoma Initially Misdiagnosed as a Racial Pigmentation: A Case Report. AB - Oral malignant melanoma (OMM) is rare, representing less than 0.5% of all oral malignancies. The most affected sites are the palate and the maxillary gingiva. Histological examination is important to establish the diagnosis of any suspicious pigmented lesion in the oral cavity, mainly if a precise clinical diagnosis is not possible. We present one case of OMM that was initially diagnosed as a racial pigmentation elsewhere 2 years earlier. Clinical examination showed multiple macules and nodules located on the hard and soft palate, gingiva and superior alveolar mucosa. These lesions were painless and presented a color variation going from dark blue to black. Histological analysis showed sheets and nests of atypical melanocytes displaying a range of shapes such as plasmacytoid, epithelioid, and round cells, located in the superficial corium extending to the deep tissues. A few tumor cells contained variable amounts of melanin. There was no invasion of blood vessels or nerve fibers. Immunohistochemical analysis revealed that the neoplastic cells were positive for HMB-45, melan-A, S-100 and negative for AE1/AE3, confirming the diagnosis of melanoma. The Ki-67 labeling index was around 25%. The patient refused any treatment and died 11 months later. PMID- 27195265 TI - Pagetoid Reticulosis: Report of Two Cases and Review of the Literature. AB - Pagetoid reticulosis is a rare variant of mycosis fungoides that presents with a large, usually single, erythematous, slowly growing scaly plaque containing an intraepidermal proliferation of neoplastic T lymphocytes. Histopathologically, this disease has distinctive attributes. In this report, we present two cases of pagetoid reticulosis, compare its microscopic features to those of 'classical' mycosis fungoides, and provide a brief review of the pertinent literature. PMID- 27195267 TI - Lung cancer screening moving forward. PMID- 27195266 TI - Diagnostic Approach to Synovial Sarcoma of the Head and Neck Illustrated by Two Cases Arising in the Face and Oral Cavity. AB - In the head and neck region, synovial sarcomas (SS) are rare tumours. We describe the diagnostic approach to SS based on two cases which developed in a 26-year-old male in the face and in a 53-year-old female on the alveolar mucosa of the upper jaw. The demographic profile of the patients was compatible with the literature. Histopathologically, both tumours presented as unencapsulated spindle cell tumours arranged into short fascicles. Although the chromosomal translocation of t(X;18)(p11.2;q11.2), transducin-like enhancer of split 1 (TLE-1) and SMARCB1 antibodies derived from gene expression studies are considered as the most sensitive makers to diagnose SS, these facilities were not available. Therefore, our cases were diagnosed as monophasic fibrous SS, utilizing a panel of immunohistochemical markers, including cytokeratins, EMA, Bcl-2, and CD99 as positive indicators and CD34, SMA, MYO-D, and S-100 as negative indicators. PAS staining was used to identify glycogen and to exclude spindle cell carcinomas and leiomyosarcoma, while Alcian blue was used to identify myxoid ground substance and to exclude nodular fasciitis. In conclusion, SS, although rare, should be included in the differential diagnosis of spindle cell tumours of the face and oral mucosa. PMID- 27195268 TI - Lung cancer epidemiology: contemporary and future challenges worldwide. AB - Over the last century, lung cancer from the rarest of diseases became the biggest cancer killer of men worldwide and in some parts of the world also of women (North America, East Asia, Northern Europe, Australia and New Zealand). In 2012 over 1.6 million of people died due to lung cancer. The cause-effect relationship between tobacco smoking and lung cancer occurrence has been proven in many studies, both ecological and clinical. In global perspective one can see the increasing tobacco consumption trend followed by ascending trends of lung cancer mortality, especially in developing countries. In some more developed countries, where the tobacco epidemics was on the rise since the beginning of the 20th century and peaked in its mid, in male population lung cancer incidence trend reversed or leveled off. Despite predicted further decline of incidence rates, the absolute number of deaths will continue to grow in these countries. In the remaining parts of the world the tobacco epidemics is still evolving what brings rapid increase of the number of new lung cancer cases and deaths. Number of lung cancer deaths worldwide is expected to grow up to 3 million until 2035. The figures will double both in men (from 1.1 million in 2012 to 2.1 million in 2035) and women (from 0.5 million in 2012 to 0.9 million in 2035) and the two-fold difference between sexes will persist. The most rapid increase is expected in Africa region (AFRO) and East Mediterranean region (EMRO). The increase of the absolute number of lung cancer deaths in more developed countries is caused mostly by population aging and in less developed countries predominantly by the evolving tobacco epidemic. PMID- 27195270 TI - Implementation and organization of lung cancer screening. AB - CT screening for lung cancer is now being implemented in the US and China on a widespread national scale but not in Europe so far. The review gives a status for the implementation process and the hurdles to overcome in the future. It also describes the guidelines and requirements for the structure and components of high quality CT screening programs. These are essential in order to achieve a successful program with the fewest possible harms and a possible mortality benefit like that documented in the American National Lung Screening Trial (NLST). In addition the importance of continued research in CT screening methods is described and discussed with focus on the great potential to further improve this method in the future for the benefit of patients and society. PMID- 27195271 TI - The importance of the regimen of screening in maximizing the benefit and minimizing the harms. AB - BACKGROUND: In CT screening for lung cancer, the regimen of screening is critical in diagnosing lung cancer early while limiting unnecessary tests and invasive procedures. The International Early Lung Cancer Action Program (I-ELCAP) has developed a regimen based on evidence collected in the I-ELCAP cohort of more than 70,000 participants. METHODS: Important in the development of the regimen is the recognition of the profound difference between the first, baseline round of screening and all subsequent rounds of repeat screening. For each person undergoing screening, the baseline round happens only once while repeat rounds will be performed annually for many years. This difference needs to be clearly recognized as it is these annual rounds which allow for identification of small, early, yet aggressive, lung cancers which have high cure rates despite their aggressiveness. The importance of nodule consistency and size are key factors in the regimen. The regimen needs to be continuously updated by incorporating advances in technology and knowledge. RESULTS: The use of the I-ELCAP regimen reduces the workup of participants in the screening program to less than 10% in the baseline round and less than 6% in the annual repeat rounds. By use of this regimen, estimated cure rate of lung cancers diagnosed under screening is 80% or higher in both baseline and annual repeat rounds. CONCLUSIONS: The I-ELCAP collaboration provides a new paradigm that answers the 2002 NCI call for multiple approaches to address relevant questions about screening and the Institute of Medicine (IOM) Roundtable on Evidence-based Medicine from the National Academy of Science's call for a "new clinical research paradigm that takes better advantage of data generated in the course of healthcare delivery would speed and improve the development of evidence for real-world decision making". PMID- 27195272 TI - Advancing and sharing the knowledge base of CT screening for lung cancer. AB - CT screening for lung cancer is gaining in acceptance and is now moving from the research domain into standard clinical practice. Coincident with this, there is also increasing awareness of the usefulness of collecting large datasets obtained in the clinical domain and how this can be used to advance practice. Toward this end, in the United States, the Centers for Medicare and Medicaid Services (CMS) are requiring data from screening to be entered into certified registries. While this is still in its early stage and only limited datasets are required, this would be particularly relevant if images as well as clinical information were collected as it will allow for additional evaluation of all imaging findings including ancillary ones and understanding how they integrate into the screening process. All of this needs to be considered in the context of how this information can be shared with a person interested in being screened. In particular, the potential benefit of screening needs to be presented in terms of what is meaningful to the individual including their chances of having lung cancer and also their chance of being cured. This is very different then presenting it in terms of mortality reduction which was never meant to be used for that purpose. Also, how findings made on the CT scans, in addition to those related to lung cancer will be meaningful to them. PMID- 27195269 TI - Risk factors assessment and risk prediction models in lung cancer screening candidates. AB - From February 2015, low-dose computed tomography (LDCT) screening entered the armamentarium of diagnostic tools broadly available to individuals at high-risk of developing lung cancer. While a huge number of pulmonary nodules are identified, only a small fraction turns out to be early lung cancers. The majority of them constitute a variety of benign lesions. Although it entails a burden of the diagnostic work-up, the undisputable benefit emerges from: (I) lung cancer diagnosis at earlier stages (stage shift); (II) additional findings enabling the implementation of a preventive action beyond the realm of thoracic oncology. This review presents how to utilize the risk factors from distinct categories such as epidemiology, radiology and biomarkers to target the fraction of population, which may benefit most from the introduced screening modality. PMID- 27195273 TI - 2016 reflections on the favorable cost-benefit of lung cancer screening. AB - This article gives a basic background on the confusing and often politicized topic of cost-benefit analysis in healthcare, using lung cancer screening as a case study. The authors are actuaries who work with the insurance industry, where real-world data is used to produce audited financial figures; other disciplines which work with cost-benefit analysis include those academic disciplines where randomized controlled trials may be perceived as the gold standard of evidence. In recent years, the finance and academic sectors of healthcare have begun to converge, as academic disciplines have come to increasingly appreciate real-world data, and insurers increasingly appreciate classical evidence-based medicine. Nevertheless, the variation of results in cost-benefit analyses for particular treatments can be bewildering to medical experts unfamiliar with real-world healthcare financing. PMID- 27195274 TI - Management of CT screen-detected lung nodule: the thoracic surgeon perspective. AB - Implementation of lung cancer CT screening programs will increase the incidence of pulmonary nodules and require multidisciplinary efforts for devising appropriate treatment plans. The role of the thoracic surgeon is paramount in leading the discussion and shaping the treatment strategies. Management of CT screen-detected lung nodules differ from conventional lung cancer nodules given their smaller size, varied histologies and potentially indolent growth. Here we present a brief overview of the thoracic surgeon's perspective on the clinical evaluation, diagnostic tests and surgical approach to these nodules in the setting of a comprehensive lung cancer screening program. PMID- 27195275 TI - Smoking cessation and lung cancer screening. AB - Smoking behavior may have a substantial influence on the overall effect of lung cancer screening. Non-randomized studies of smoking behavior during screening have indicated that computer tomography (CT) screening induces smoking cessation. Randomized studies have further elaborated that this effect has to do with participation in screening alone and not dependent on the CT scan. Participants in both CT and control arm in randomized screening trials had higher smoking abstinence rate compared to that of the general population. A positive screening test seems to further promote smoking cessation and decrease smoking relapse rate. Also low smoking dependency and high motivation to quit smoking at baseline predicted smoking abstinence in screening trials. Lung cancer screening therefore seems to be a teachable moment for smoking cessation. Targeted smoking cessation counselling should be an integrated part of future lung cancer screening trials. PMID- 27195276 TI - Biomarkers of risk to develop lung cancer in the new screening era. AB - Low-dose computed tomography for high-risk individuals has for the first time demonstrated unequivocally that early detection save lives. The currently accepted screening strategy comes at the cost of a high rate of false positive findings while still missing a large percentage of the cases. Therefore, there is increasing interest in developing strategies to better estimate the risk of an individual to develop lung cancer, to increase the sensitivity of the screening process, to reduce screening costs and to reduce the numbers of individuals harmed by screening and follow-up interventions. New molecular biomarkers candidates show promise to improve lung cancer outcomes. This review discusses the current state of biomarker research in lung cancer screening with the primary focus on risk assessment. PMID- 27195278 TI - Lung cancer screening in patients with chronic obstructive pulmonary disease. AB - Lung cancer and chronic obstructive pulmonary disease (COPD) are two intimately related diseases, with great impact on public health. Annual screening using low dose computed tomography (LDCT) of the chest significantly reduces mortality due to lung cancer, and several scientific societies now recommend this technique. COPD, defined by the presence of airflow obstruction [forced expiratory volume and forced vital capacity (FVC) ratio less than 0.70], and their clinical phenotypes, namely emphysema and chronic bronchitis, have been associated with increased lung cancer risk. Several epidemiological studies, including lung cancer screening trials, have found a 2- to 4-fold increase in lung cancer risk in patients with COPD when compared to individuals without airflow obstruction. Part of the risk attributed to airflow obstruction appears to be derived from the presence of radiographic emphysema. The latter has proven to be an important lung cancer risk factor in smokers without airflow obstruction and even in never smokers. This evidence supports the idea of including patients with COPD and/or emphysema in lung cancer screening programs. There is evidence that lung cancer screening in this population is effective and can potentially reduce mortality. Specific lung cancer risk scores have been developed for patients with COPD [COPD lung cancer screening score (LUCSS) and COPD-LUCSS-diffusing capacity for carbon monoxide (DLCO)] to identify those at high risk. A multidisciplinary approach for an adequate patient selection, especially of patients with severe disease, is key to maximize benefits and reduce harms from lung cancer screening in this population. Patients with COPD included in lung cancer screening programs could also benefit from other interventions, such as smoking cessation and adequate treatment. PMID- 27195277 TI - Coronary artery calcification in clinical practice: what we have learned and why should it routinely be reported on chest CT? AB - The recent acceptance of low dose chest computed tomography (LDCT) as a screening modality for early lung cancer detection will significantly increase the number of LDCT among high risk population. The target subjects are at the same time at high risk to develop cardiovascular (CV) events. The routine report on coronary artery calcification (CAC) will therefore, enhances the screening benefit by providing the clinicians with an additive powerful risk stratification tool for the management or primary prevention of CV events. This review will provide the radiologists with helpful information for the daily practice regarding on what is CAC, its clinical applications and how to diagnose, quantify and report on CAC while reading the LDCT. PMID- 27195279 TI - Transcriptomic Analysis of Resistant and Susceptible Bombyx mori Strains Following BmNPV Infection Provides Insights into the Antiviral Mechanisms. AB - Purpose. To decipher transcriptomic changes and related genes with potential functions against Bombyx mori nucleopolyhedrovirus infection and to increase the understanding of the enhanced virus resistance of silkworm on the transcriptomic level. Methods. We assembled and annotated transcriptomes of the Qiufeng (susceptible to infection) and QiufengN (resistant to infection) strains and performed comparative analysis in order to decipher transcriptomic changes and related genes with potential functions against BmNPV infection. Results. A total of 78,408 SNPs were identified in the Qiufeng strain of silkworm and 56,786 SNPs were identified in QiufengN strain. Besides, novel AS events were found in these 2 strains. In addition, 1,728 DEGs were identified in the QiufengN strain compared with Qiufeng strain. These DEGs were involved in GO terms related to membrane, metabolism, binding and catalytic activity, cellular processes, and organismal systems. The highest levels of gene representation were found in oxidative phosphorylation, phagosome, TCA cycle, arginine and proline metabolism, and pyruvate metabolism. Additionally, COG analysis indicated that DEGs were involved in "amino acid transport and metabolism" and "carbohydrate transport and metabolism." Conclusion. We identified a series of major pathological changes in silkworm following infection and several functions were related to the antiviral mechanisms of silkworm. PMID- 27195280 TI - The Microbiome of Animals: Implications for Conservation Biology. AB - In recent years the human microbiome has become a growing area of research and it is becoming clear that the microbiome of humans plays an important role for human health. Extensive research is now going into cataloging and annotating the functional role of the human microbiome. The ability to explore and describe the microbiome of any species has become possible due to new methods for sequencing. These techniques allow comprehensive surveys of the composition of the microbiome of nonmodel organisms of which relatively little is known. Some attention has been paid to the microbiome of insect species including important vectors of pathogens of human and veterinary importance, agricultural pests, and model species. Together these studies suggest that the microbiome of insects is highly dependent on the environment, species, and populations and affects the fitness of species. These fitness effects can have important implications for the conservation and management of species and populations. Further, these results are important for our understanding of invasion of nonnative species, responses to pathogens, and responses to chemicals and global climate change in the present and future. PMID- 27195282 TI - LED Curing Lights and Temperature Changes in Different Tooth Sites. AB - Objectives. The aim of this in vitro study was to assess thermal changes on tooth tissues during light exposure using two different LED curing units. The hypothesis was that no temperature increase could be detected within the dental pulp during polymerization irrespective of the use of a composite resin or a light-curing unit. Methods. Caries-free human first molars were selected, pulp residues were removed after root resection, and four calibrated type-J thermocouples were positioned. Two LED lamps were tested; temperature measurements were made on intact teeth and on the same tooth during curing of composite restorations. The data was analyzed by one-way analysis of variance (ANOVA), Wilcoxon test, Kruskal-Wallis test, and Pearson's chi (2). After ANOVA, the Bonferroni multiple comparison test was performed. Results. Polymerization data analysis showed that in the pulp chamber temperature increase was higher than that without resin. Starlight PRO, in the same condition of Valo lamp, showed a lower temperature increase in pre- and intrapolymerization. A control group (without composite resin) was evaluated. Significance. Temperature increase during resin curing is a function of the rate of polymerization, due to the exothermic polymerization reaction, the energy from the light unit, and time of exposure. PMID- 27195281 TI - Does Citrulline Have Protective Effects on Liver Injury in Septic Rats? AB - Citrulline (Cit) supplementation was proposed to serve as a therapeutic intervention to restore arginine (Arg) concentrations and improve related functions in sepsis. This study explored whether citrulline had positive effects on liver injury and cytokine release in the early stages of sepsis. The cecal ligation and puncture (CLP) model was utilized in our study. Rats were divided into four groups: normal, Cit, CLP, and CLP+Cit. The CLP group and CLP+Cit group were separated into 6-, 12-, and 24-hour groups, according to the time points of sacrifice after surgery. Intragastric administration of L-citrulline was applied to rats in Cit and CLP+Cit groups before surgery. Serum AST and ALT levels and levels of MDA, SOD, NO, and iNOS in the liver tissues were evaluated. Plasma concentrations of Cit and Arg were assessed using HPLC-MS/MS. Serum concentrations of cytokines and chemokines were calculated by Luminex. Results showed SOD activities of CLP+Cit groups were significantly higher than that of CLP groups, contrasting with the MDA and NO levels which were significantly lower in CLP+Cit groups than in CLP groups. In addition, plasma concentrations of TNF alpha, IL-6, and IL-1beta were significantly lower in the CLP+Cit 6-hour group than in the CLP 6-hour group. PMID- 27195283 TI - Pressure Drop in Tortuosity/Kinking of the Internal Carotid Artery: Simulation and Clinical Investigation. AB - Background. Whether carotid tortuosity/kinking of the internal carotid artery leads to cerebral ischemia remains unclear. There is very little research about the hemodynamic variation induced by carotid tortuosity/kinking in the literature. The objective of this study was to research the blood pressure changes induced by carotid tortuosity/kinking. Methods. We first created a geometric model of carotid tortuosity/kinking. Based on hemodynamic boundary conditions, the hemodynamics of carotid tortuosity and kinking were studied via a finite element simulation. Then, an in vitro system was built to validate the numerical simulation results. The mean arterial pressure changes before and after carotid kinking were measured using pressure sensors in 12 patients with carotid kinking. Results. Numerical simulation revealed that the pressure drops increased with increases in the kinking angles. Clinical tests and in vitro experiments confirmed the numerical simulation results. Conclusions. Carotid kinking leads to blood pressure reduction. In certain conditions, kinking may affect the cerebral blood supply and be associated with cerebral ischemia. PMID- 27195284 TI - Herpes Simplex Virus Type 1 and Type 2 Infection Increases Atherosclerosis Risk: Evidence Based on a Meta-Analysis. AB - Objective. The aim of our study was to evaluate the relation of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infection with the risk of atherosclerosis (AS). Methods. A systematic literature search was performed through three electronic databases. The pooled odds ratio (OR) and corresponding 95% confidence interval (CI) were used to assess the effect of HSV-1 and HSV-2 infection on AS risk. Results. 17 studies were available for meta-analysis of HSV 1 infection and AS risk and seven studies for meta-analysis of HSV-2 infection and AS risk. Subjects exposed to HSV-1 infection exhibited an increased risk of AS (OR = 1.77; 95% CI: 1.40-2.23; P < 0.001). And consistent elevated AS risks for HSV-1 positive subjects were found in all subgroup analysis of disease type, region, male proportion, and age. HSV-2 positive subjects demonstrated significantly increased AS risk (OR = 1.37; 95% CI: 1.13-1.67; P < 0.005). In subgroup analysis, elevated AS risks were only observed in myocardial ischemia group, male proportion >60% group, and age <=60-year-old group. Conclusion. Our meta-analysis indicated that HSV-1 and HSV-2 infection could increase the risk of contracting AS. PMID- 27195285 TI - Recent Advances in Treatments of Primary Focal Segmental Glomerulosclerosis in Children. AB - Focal segmental glomerulosclerosis (FSGS) is a nephrotic syndrome. Up to around 80% of cases of primary FSGS are resistant to steroid treatment. A large proportion of patients with steroid-resistant FSGS progress to end-stage renal disease. The purpose of treatment is to obtain a complete remission of proteinuria, a necessary step that precedes improved renal survival and reduces the risk of progression to chronic kidney disease. When this is not possible, the secondary goal is a partial remission of proteinuria. Reduction or remission of proteinuria is the most important factor predictive of renal survival. We will review the current updated strategies for treatment of primary FSGS in children, including traditional therapies consisting of corticosteroids and calcineurin inhibitors and novel therapies such as rituximab, abatacept, adalimumab, and fresolimumab. PMID- 27195286 TI - Clinical Outcome and Prognostic Factors of Intensity-Modulated Radiotherapy for T4 Stage Nasopharyngeal Carcinoma. AB - Objective. To analyze the clinical outcomes and prognostic factors of intensity modulated radiotherapy (IMRT) for T4 stage nasopharyngeal carcinoma (NPC). Methods. Between March 2005 and March 2010, 110 patients with T4 stage NPC without distant metastases were treated. All patients received IMRT. Induction and/or concurrent chemotherapy were given. 47 (42.7%) patients received IMRT replanning. Results. The 5-year local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) rates were 90.1%, 97.0%, 67.5%, 63.9%, and 64.5%, respectively. Eleven patients experienced local regional failure and total distant metastasis occurred in 34 patients. 45 patients died and 26 patients died of distant metastasis alone. The 5-year LRFS rates were 97.7% and 83.8% for the patients that received and did not receive IMRT replanning, respectively (P = 0.023). Metastasis to the retropharyngeal lymph nodes (RLN) was associated with inferior 5-year OS rate (61.0% versus 91.7%, P = 0.034). The gross tumor volume of the right/left lymph nodes (GTVln) was an independent prognostic factor for DMFS (P = 0.006) and PFS (P = 0.018). GTVln was with marginal significance as the prognostic factor for OS (P = 0.050). Conclusion. IMRT provides excellent local-regional control for T4 stage NPC. Benefit of IMRT replanning may be associated with improvement in local control. Incorporating GTVln into the N staging system may provide better prognostic information. PMID- 27195287 TI - Differences in Knowledge, Attitude, and Behavior towards HIV/AIDS and Sexually Transmitted Infections between Sexually Active Foreign and Chinese Medical Students. AB - Although the prevalence of human immunodeficiency virus (HIV) decreased in the last decade worldwide, the number of deaths due to HIV/AIDS and communicable diseases including syphilis, hepatitis, and tuberculosis had dramatically increased in developing countries. Education and behavior are incredibly important factors to prevent these diseases' spread. This study highlights the range of differences in knowledge, attitude, and behavior of 434 sexually active medical students towards HIV/AIDS and sexually transmitted infections (STIs). Because the surveyed population constitutes the forefront of healthcare providers and was originated from different area of the world, this is the first time a study sought to investigate the behavioral attitude of this group of population irrespective of the three levels of their academic and professional knowledge. Several factors including sociodemographic characteristics, sexual behavior, HIV/AIDS, and STIs related patterns play a key role in medical student attitude and behavior towards people infected with HIV/AIDS and STIs. Our findings add consistent value in prior studies which aimed to stop new infections and also imply further investigations on the management of the studied infections by medical students. The present study arouses much interest among participants and provides evidence of reinforcing medical students' education on HIV/AIDS and STIs. PMID- 27195288 TI - Efficacy and Safety of Silodosin and Dutasteride Combination Therapy in Acute Urinary Retention due to Benign Prostatic Hyperplasia: A Single-Arm Prospective Study. AB - This study aimed to assess the efficacy of combination therapy with dutasteride and silodosin in patients with acute urinary retention (AUR) caused by benign prostatic hyperplasia (BPH). Eighty consecutive patients with a first episode of AUR were enrolled in this study. All patients received silodosin 8 mg and dutasteride 0.5 mg daily. Trial without catheter (TWOC) was attempted every 2 weeks until 12 weeks after the initiation of medication. The primary endpoint was the rate of catheter-free status at 12 weeks. Voided volume (VV), postvoid residual urine (PVR), uroflowmetry, International Prostatic Symptoms Score (IPSS), and quality of life due to urinary symptoms (IPSS-QOL) were also measured. All patients were followed up for more than 12 weeks and were included in this analysis. The success rate of TWOC at 12 weeks was 88.8%. VV and maximum urinary flow rate were significantly higher at 2, 4, 8, and 12 weeks compared with the time of AUR (P < 0.001). IPSS and IPSS-QOL were significantly lower at 2, 4, 8, and 12 weeks compared with the time of AUR (P < 0.001). In conclusion, a combination of dutasteride and silodosin therapy may be effective and safe for patients with AUR due to BPH. PMID- 27195289 TI - Skeletal Muscle Remodelling as a Function of Disease Progression in Amyotrophic Lateral Sclerosis. AB - Muscle weakness is considered the pivotal sign of amyotrophic lateral sclerosis (ALS). Knowledge about the skeletal muscle degeneration/regeneration process and the myogenic potential is limited in ALS patients. Therefore, we investigate these processes in a time course perspective by analysing skeletal muscle biopsies from ALS patients collected before and after a 12-week period of normal daily activities and compare these with healthy age-matched control tissue. We do this by evaluating mRNA and protein (immunohistochemical) markers of regeneration, neurodegeneration, myogenesis, cell cycle regulation, and inflammation. Our results show morphological changes indicative of active denervation and reinnervation and an increase in small atrophic fibres. We demonstrate differences between ALS and controls in pathways controlling skeletal muscle homeostasis, cytoskeletal and regenerative markers, neurodegenerative factors, myogenic factors, cell cycle determinants, and inflammatory markers. Our results on Pax7 and MyoD protein expression suggest that proliferation and differentiation of skeletal muscle stem cells are affected in ALS patients, and the myogenic processes cannot overcome the denervation-induced wasting. PMID- 27195291 TI - Increased ZAP70 Is Involved in Dry Skin Pruritus in Aged Mice. AB - Dry skin pruritus is common in the elderly. Recent reports show that T-cell signal path is involved in dry skin pruritus. Zeta-chain-associated protein kinase 70 (ZAP70), as a T-cell receptor, may induce interleukin 2 (IL-2) secretion and promote nerve growth factor (NGF) secretion in skin. This study aimed to detect the alteration of ZAP70 in a mice model with dry skin pruritus. The C57BL mice with 5 months and 22 months were used as experimental animal. Following a 5-day period of treatment of back with a mixture of acetone-diethyl ether-water (AEW), mice exhibited a significant increase in spontaneous scratching behavior directed to the treated back compared to control animals in which back was similarly treated with water only (W). After AEW process, spontaneous scratching in 22-month AEW mice was increased compared to 5-month AEW mice. Western blot and real-time quantitative PCR data analysis showed that ZAP70 expression was significantly increased in 22-month AEW mice compared with 5-month AEW mice. ELISA data showed that secretions of IL-2 and NGF in 22-month AEW mice were higher than 5-month AEW mice. Our results indicate that increased ZAP70 is involved in dry skin in elderly pruritus. Increased secretion of IL-2 and NGF may induce dry skin itch. PMID- 27195290 TI - Valproic Acid Prevents Renal Dysfunction and Inflammation in the Ischemia Reperfusion Injury Model. AB - Ischemia-reperfusion injury (IRI) is a major contributor to acute kidney injury (AKI). At present, there are no effective therapies to prevent AKI. The aim of this study was to analyse whether valproic acid (VPA), a histone deacetylase inhibitor with anti-inflammatory properties, prevents renal IRI. Male Wistar rats were divided into three groups: SHAM rats were subjected to a SHAM surgery, IRI rats underwent bilateral renal ischemia for 45 min, and IRI + VPA rats were treated with VPA at 300 mg/kg twice daily 2 days before bilateral IRI. Animals were euthanized at 48 hours after IRI. VPA attenuated renal dysfunction after ischemia, which was characterized by a decrease in BUN (mg/dL), serum creatinine (mg/dL), and FENa (%) in the IRI + VPA group (39 +/- 11, 0.5 +/- 0.05, and 0.5 +/ 0.06, resp.) compared with the IRI group (145 +/- 35, 2.7 +/- 0.05, and 4.9 +/- 1, resp.; p < 0.001). Additionally, significantly lower acute tubular necrosis grade and number of apoptotic cells were found in the IRI + VPA group compared to the IRI group (p < 0.001). Furthermore, VPA treatment reduced inflammatory cellular infiltration and expression of proinflammatory cytokines. These data suggest that VPA prevents the renal dysfunction and inflammation that is associated with renal IRI. PMID- 27195292 TI - Tricellular Tight Junctions in the Inner Ear. AB - Tight junctions (TJs) are structures that seal the space between the epithelial cell sheets. In the inner ear, the barrier function of TJs is indispensable for the separation of the endolymphatic and perilymphatic spaces, which is essential for the generation and maintenance of the endocochlear potential (EP). TJs are formed by the intercellular binding of membrane proteins, known as claudins, and mutations in these proteins cause deafness in humans and mice. Within the epithelial cell sheet, however, a bound structure is present at the site where the corners of three cells meet (tricellular tight junctions (tTJs)), and the maintenance of the barrier function at this location cannot be explained by the claudins alone. Tricellulin and the angulin family of proteins (angulin-1/LSR, angulin-2/ILDR1, and angulin-3/ILDR2) have been identified as tTJ-associated proteins. Tricellulin and ILDR1 are localized at the tTJ and alterations in these proteins have been reported to be involved in deafness. In this review, we will present the current state of knowledge for tTJs. PMID- 27195293 TI - In Vitro Cytokine Expression and In Vivo Healing and Inflammatory Response to a Collagen-Coated Synthetic Bone Filler. AB - The goal of the present work was to investigate the relationship between in vivo healing and inflammatory response and in vitro cytokine expression by macrophages of a synthetic bone filler (25% hydroxylapatite-75% beta-tricalcium phosphate) bearing a surface nanolayer of collagen. A clinically accepted, state-of-the-art xenograft material was used as a "negative control," that is, as a material that provides the correct clinical response for the intended use. In vitro data show that both materials exert a very low stimulation of proinflammatory cytokines by macrophages, and this was confirmed by the very mild inflammatory response detected in in vivo tests of local response in a rabbit model. Also, in vitro findings suggest a different mechanism of healing for the test and the control material, with a higher regenerative activity for the synthetic, resorbable filler, as confirmed by in vivo observation and literature reports. Thus, the simple in vitro model adopted provides a reasonable forecast of in vivo results, suggesting that new product development can be guided by in vitro tuning of cell materials interactions. PMID- 27195294 TI - The Effect of Diabetes Medication on Cognitive Function: Evidence from the PATH Through Life Study. AB - Objective. To examine the effect of diabetes treatment on change of measures of specific cognitive domains over 4 years. Research Design and Methods. The sample was drawn from a population-based cohort study in Australia (the PATH Through Life Study) and comprised 1814 individuals aged 65-69 years at first measurement, of whom 211 were diagnosed with diabetes. Cognitive function was measured using 10 neuropsychological tests. The effect of type of diabetes treatment (diet, oral hypoglycemic agents, and insulin) on measures of specific cognitive domains was assessed using Generalized Linear Models adjusted for age, sex, education, smoking, physical activity level, BMI, and hypertension. Results. Comparison of cognitive function between diabetes treatment groups showed no significant effect of type of pharmacological treatment on cognitive function compared to diet only group or no diabetes group. Of those on oral hypoglycaemic treatment only, participants who used metformin alone had better cognitive function at baseline for the domains of verbal learning, working memory, and executive function compared to participants on other forms of diabetic treatment. Conclusion. This study did not observe significant effect from type of pharmacological treatment for diabetes on cognitive function except that participants who only used metformin showed significant protective effect from metformin on domain of verbal learning, working memory, and executive function. PMID- 27195295 TI - A Comprehensive Curation Shows the Dynamic Evolutionary Patterns of Prokaryotic CRISPRs. AB - Motivation. Clustered regularly interspaced short palindromic repeat (CRISPR) is a genetic element with active regulation roles for foreign invasive genes in the prokaryotic genomes and has been engineered to work with the CRISPR-associated sequence (Cas) gene Cas9 as one of the modern genome editing technologies. Due to inconsistent definitions, the existing CRISPR detection programs seem to have missed some weak CRISPR signals. Results. This study manually curates all the currently annotated CRISPR elements in the prokaryotic genomes and proposes 95 updates to the annotations. A new definition is proposed to cover all the CRISPRs. The comprehensive comparison of CRISPR numbers on the taxonomic levels of both domains and genus shows high variations for closely related species even in the same genus. The detailed investigation of how CRISPRs are evolutionarily manipulated in the 8 completely sequenced species in the genus Thermoanaerobacter demonstrates that transposons act as a frequent tool for splitting long CRISPRs into shorter ones along a long evolutionary history. PMID- 27195296 TI - The Possible Roles of Biological Bone Constructed with Peripheral Blood Derived EPCs and BMSCs in Osteogenesis and Angiogenesis. AB - This study aimed to determine the possible potential of partially deproteinized biologic bone (PDPBB) seeded with bone marrow stromal cells (BMSCs) and endothelial progenitor cells (EPCs) in osteogenesis and angiogenesis. BMSCs and EPCs were isolated, identified, and cocultured in vitro, followed by seeding on the PDPBB. Expression of osteogenesis and vascularization markers was quantified by immunofluorescence (IF) staining, immunohistochemistry (IHC), and quantitive real-time polymerase chain reaction (qRT-PCR). Scanning electron microscope (SEM) was also employed to further evaluate the morphologic alterations of cocultured cells in the biologic bone. Results demonstrated that the coculture system combined with BMSCs and EPCs had significant advantages of (i) upregulating the mRNA expression of VEGF, Osteonectin, Osteopontin, and Collagen Type I and (ii) increasing ALP and OC staining compared to the BMSCs or EPCs only group. Moreover, IHC staining for CD105, CD34, and ZO-1 increased significantly in the implanted PDPBB seeded with coculture system, compared to that of BMSCs or EPCs only, respectively. Summarily, the present data provided evidence that PDPBB seeded with cocultured system possessed favorable cytocompatibility, provided suitable circumstances for different cell growth, and had the potential to provide reconstruction for cases with bone defection by promoting osteogenesis and angiogenesis. PMID- 27195297 TI - Roe Protein Hydrolysates of Giant Grouper (Epinephelus lanceolatus) Inhibit Cell Proliferation of Oral Cancer Cells Involving Apoptosis and Oxidative Stress. AB - Roe protein hydrolysates were reported to have antioxidant property but the anticancer effects were less addressed, especially for oral cancer. In this study, we firstly used the ultrafiltrated roe hydrolysates (URH) derived from giant grouper (Epinephelus lanceolatus) to evaluate the impact of URH on proliferation against oral cancer cells. We found that URH dose-responsively reduced cell viability of two oral cancer cells (Ca9-22 and CAL 27) in terms of ATP assay. Using flow cytometry, URH-induced apoptosis of Ca9-22 cells was validated by morphological features of apoptosis, sub-G1 accumulation, and annexin V staining in dose-responsive manners. URH also induced oxidative stress in Ca9-22 cells in terms of reactive oxygen species (ROS)/superoxide generations and mitochondrial depolarization. Taken together, these data suggest that URH is a potential natural product for antioral cancer therapy. PMID- 27195298 TI - Association between Polymorphisms in Interleukins 4 and 13 Genes and Chronic Periodontitis in a Han Chinese Population. AB - Chronic periodontitis (CP) is one of the most common chronic inflammatory diseases and cytokines play a pivotal role in the regulation of immune response. Interleukin-4 (IL-4) and interleukin-13 (IL-13) are anti-inflammatory cytokines and several polymorphisms of them have been proved involved in periodontal disease. This study aimed to evaluate whether three single nucleotide polymorphisms (SNPs), rs2070874 and rs2243248 from IL4 and rs1800925 from IL13, are associated with CP in a Han Chinese population consisting of 440 moderate or severe CP patients and 324 healthy controls. Genomic DNA extracted from buccal epithelial cells of the included participants were genotyped using a matrix assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry method. No significant association between rs2070874 or rs1800925 and CP was found, while the frequencies of rs2243248 and two haplotypes C-G-T and C-T-T showed significant differences between the two groups. The results suggest that the polymorphism rs2243248 and haplotypes C-G-T and C-T-T may be associated with CP susceptibility in the present Han Chinese population. PMID- 27195299 TI - Technical Aspects on the Use of Ultrasonic Bone Shaver in Spine Surgery: Experience in 307 Patients. AB - Aim. We discuss technical points, the safety, and efficacy of ultrasonic bone shaver in various spinal surgeries within our own series. Methods. Between June 2010 and January 2014, 307 patients with various spinal diseases were operated on with the use of an ultrasonic bone curette with microhook shaver (UBShaver). Patients' data were recorded and analyzed retrospectively. The technique for the use of the device is described for each spine surgery procedure. Results. Among the 307 patients, 33 (10.7%) cases had cervical disorder, 17 (5.5%) thoracic disorder, 3 (0.9%) foramen magnum disorder, and 254 (82.7%) lumbar disorders. Various surgical techniques were performed either assisted or alone by UBShaver. The duration of the operations and the need for blood replacement were relatively low. The one-year follow-up with Neck Disability Index (NDI) and Oswestry Disability Index (ODI) scores were improved. We had 5 cases of dural tears (1.6%) in patients with lumbar spinal disease. No neurological deficit was found in any patients. Conclusion. We recommend this device as an assistant tool in various spine surgeries and as a primary tool in foraminotomies. It is a safe device in spine surgery with very low complication rate. PMID- 27195300 TI - Steroid Tumor Environment in Male and Female Mice Model of Canine and Human Inflammatory Breast Cancer. AB - Canine inflammatory mammary cancer (IMC) shares clinical and histopathological characteristics with human inflammatory breast cancer (IBC) and has been proposed as a good model for studying the human disease. The aim of this study was to evaluate the capacity of female and male mice to reproduce IMC and IBC tumors and identify the hormonal tumor environment. To perform the study sixty 6-8-week-old male and female mice were inoculated subcutaneously with a suspension of 10(6)IPC 366 and SUM149 cells. Tumors and serum were collected and used for hormonal analysis. Results revealed that IPC-366 reproduced tumors in 90% of males inoculated after 2 weeks compared with 100% of females that reproduced tumor at the same time. SUM149 reproduced tumors in 40% of males instead of 80% of females that reproduced tumors after 4 weeks. Both cell lines produce distant metastasis in lungs being higher than the metastatic rates in females. EIA analysis revealed that male tumors had higher T and SO4E1 concentrations compared to female tumors. Serum steroid levels were lower than those found in tumors. In conclusion, IBC and IMC male mouse model is useful as a tool for IBC research and those circulating estrogens and intratumoral hormonal levels are crucial in the development and progression of tumors. PMID- 27195301 TI - Collagen V Is a Potential Substrate for Clostridial Collagenase G in Pancreatic Islet Isolation. AB - The clostridial collagenases, H and G, play key roles in pancreatic islet isolation. Collagenases digest the peptide bond between Yaa and the subsequent Gly in Gly-Xaa-Yaa repeats. To fully understand the pancreatic islet isolation process, identification of the collagenase substrates in the tissue is very important. Although collagen types I and III were reported as possible substrates for collagenase H, the substrate for collagenase G remains unknown. In this study, collagen type V was focused upon as the target for collagenases. In vitro digestion experiments for collagen type V were performed and analyzed by SDS-PAGE and mass spectrometry. Porcine pancreatic tissues were digested in vitro under three conditions and observed during digestion. The results revealed that collagen type V was only digested by collagenase G and that the digestion was initiated from the N-terminal part. Tissue degradation during porcine islet isolation was only observed in the presence of both collagenases H and G. These findings suggest that collagen type V is one of the substrates for collagenase G. The enzymatic activity of collagenase G appears to be more important for pancreatic islet isolation in large mammals such as pigs and humans. PMID- 27195302 TI - Variations in the Obesity Gene "LEPR" Contribute to Risk of Type 2 Diabetes Mellitus: Evidence from a Meta-Analysis. AB - Leptin is a hormone protein regulating food intake and energy expenditure. A number of studies have evaluated the genetic effect of leptin (LEP) and leptin receptor (LEPR) genes on T2DM. This study aimed to investigate the association between these gene polymorphisms and T2DM by a systematic review and meta analysis. Published studies were identified through extensive search in PubMed and EMBASE. A total of 5143 T2DM cases and 5021 controls from 14 articles were included in this study. Five functional variants in LEPR were well evaluated. Meta-analysis showed that rs1137101 (p.R223Q) was significantly associated with T2DM in all genetic models: allele model (OR = 1.27, 95% confidence interval (CI) = 1.13-1.42), dominant model (OR = 1.19, 95% CI = 1.05-1.35), homozygote model (OR = 1.82, 95% CI = 1.38-2.39), and recessive model (OR = 1.75, 95% CI = 1.35 2.28), with minimal heterogeneity and no indication of publication bias. Similar associations with T2DM were also found for rs62589000 (p.P1019P) and 3'UTR ins/del, although the data was obtained from a small number of studies. For the other two polymorphisms rs1137100 (p.R109K) and rs8179183 (p.K656N), they were not significantly associated with T2DM. Our results provide robust evidences for the genetic association of rs1137101 (p.R223Q) in LEPR with T2DM susceptibility. PMID- 27195304 TI - Effects of a Moderately Lower Temperature on the Proliferation and Degranulation of Rat Mast Cells. AB - Mast cells are traditionally considered as key effector cells in IgE-mediated allergic diseases. However, the roles of mast cells have also been implicated in diverse physiological and pathological processes. Mast cells are distributed in various organs and tissues of various species. Some of the organs and tissues, such as testis, skin, and the upper part of the respiratory tract, have a temperature that is lower than the body's core temperature. The purpose of the present study was to investigate the effects of a lower temperature on the proliferation and degranulation of rat mast cells. Here, we demonstrate that cell growth was retarded at 35 degrees C compared to 37 degrees C for both rat peritoneal mast cells (RPMC) and RBL-2H3, a rat mast cell line. Furthermore, RPMC became more susceptible to degranulation at 35 degrees C compared to 37 degrees C. In contrast, degranulation of RBL-2H3 was not as sensitive to temperature change as RPMC. The functionality of mast cells in unique organs with a lower temperature warrants further analysis. PMID- 27195303 TI - Phenotyping of Leukocytes and Leukocyte-Derived Extracellular Vesicles. AB - Extracellular vesicles (EVs) have a demonstrated involvement in modulating the immune system. It has been proposed that EVs could be used as biomarkers for detection of inflammatory and immunological disorders. Consequently, it is of great interest to investigate EVs in more detail with focus on immunological markers. In this study, five major leukocyte subpopulations and the corresponding leukocyte-derived EVs were phenotyped with focus on selected immunological lineage-specific markers and selected vesicle-related markers. The leukocyte derived EVs displayed phenotypic differences in the 34 markers investigated. The majority of the lineage-specific markers used for identification of the parent cell types could not be detected on EVs released from monocultures of the associated cell types. In contrast, the vesicular presentation of CD9, CD63, and CD81 correlated to the cell surface expression of these markers, however, with few exceptions. Furthermore, the cellular expression of CD9, CD63, and CD81 varied between leukocytes present in whole blood and cultured leukocytes. In summary, these data demonstrate that the cellular and vesicular presentation of selected lineage-specific and vesicle-related markers may differ, supporting the accumulating observations that sorting of molecular cargo into EVs is tightly controlled. PMID- 27195305 TI - Demographics, referral patterns and management of patients accessing the Welsh Eye Care Service. AB - BACKGROUND: The Primary Eyecare Acute Referral Service (PEARS) and the Wales Eye Health Examination (WEHE) operate as enhanced optometry services for patients residing in Wales, enabling the examination of a patient presenting with an acute eye problem (PEARS) or the examination of patients at higher risk of eye disease (WEHE). The purpose of the study is to assess the demographics of patients accessing these services, referral patterns and clinical management in one Health Board in Wales (Aneurin Bevan University Health Board). METHODS: Information from 2302 patients accessing the services was prospectively collected. The following information was obtained: type of examination (PEARS or WEHE), patient age, gender, self-referral or general practitioner (GP) referral and clinical management (no further action, monitor by optometrist or ophthalmic medical practitioner [OMP], refer to the Hospital Eye Service [HES], or refer to GP). RESULTS: There were 1791 (77.8 %) PEARS examinations and 511 (22.2 %) WEHE. There were 1379 (59.9 %) females with a mean age of 58.61 (+/-19.75) and 923 (40.1 %) males with a mean age of 56.11 (+/-20.42). The majority of patients were self referrals compared to GP-referrals (1793 [77.9 %] versus 509 [22.1 %] respectively). Sub-analysis indicated similar numbers of self-referrals compared to GP-referrals for the WEHE only (297 [58.1 %] versus 214 [41.9 %] respectively) but greater numbers of self-referrals for the PEARS examinations only (1496 [83.5 %] versus 295 [16.5 %] respectively). For management, 75 % of patients were monitored by their optometrist or OMP, 17 % required referral to the HES and 8 % required referral to their GP. CONCLUSIONS: Higher numbers of females accessed both PEARS and WEHE services and the majority of patients self-referred. These findings have important implications for public health campaigns both for targeting specific groups (e.g. male patients) and increasing awareness among GPs. PMID- 27195306 TI - User-composable Electronic Health Record Improves Efficiency of Clinician Data Viewing for Patient Case Appraisal: A Mixed-Methods Study. AB - BACKGROUND: Challenges in the design of electronic health records (EHRs) include designing usable systems that must meet the complex, rapidly changing, and high stakes information needs of clinicians. The ability to move and assemble elements together on the same page has significant human-computer interaction (HCI) and efficiency advantages, and can mitigate the problems of negotiating multiple fixed screens and the associated cognitive burdens. OBJECTIVE: We compare MedWISE a novel EHR that supports user-composable displays-with a conventional EHR in terms of the number of repeat views of data elements for patient case appraisal. DESIGN AND METHODS: The study used mixed-methods for examination of clinical data viewing in four patient cases. The study compared use of an experimental user composable EHR with use of a conventional EHR, for case appraisal. Eleven clinicians used a user-composable EHR in a case appraisal task in the laboratory setting. This was compared with log file analysis of the same patient cases in the conventional EHR. We investigated the number of repeat views of the same clinical information during a session and across these two contexts, and compared them using Fisher's exact test. RESULTS: There was a significant difference (p<.0001) in proportion of cases with repeat data element viewing between the user-composable EHR (14.6 percent) and conventional EHR (72.6 percent). DISCUSSION AND CONCLUSION: Users of conventional EHRs repeatedly viewed the same information elements in the same session, as revealed by log files. Our findings are consistent with the hypothesis that conventional systems require that the user view many screens and remember information between screens, causing the user to forget information and to have to access the information a second time. Other mechanisms (such as reduction in navigation over a population of users due to interface sharing, and information selection) may also contribute to increased efficiency in the experimental system. Systems that allow a composable approach that enables the user to gather together on the same screen any desired information elements may confer cognitive support benefits that can increase productive use of systems by reducing fragmented information. By reducing cognitive overload, it can also enhance the user experience. PMID- 27195307 TI - A New Framework and Prototype Solution for Clinical Decision Support and Research in Genomics and Other Data-intensive Fields of Medicine. AB - INTRODUCTION: In genomics and other fields, it is now possible to capture and store large amounts of data in electronic medical records (EMRs). However, it is not clear if the routine accumulation of massive amounts of (largely uninterpretable) data will yield any health benefits to patients. Nevertheless, the use of large-scale medical data is likely to grow. To meet emerging challenges and facilitate optimal use of genomic data, our institution initiated a comprehensive planning process that addresses the needs of all stakeholders (e.g., patients, families, healthcare providers, researchers, technical staff, administrators). Our experience with this process and a key genomics research project contributed to the proposed framework. FRAMEWORK: We propose a two pronged Genomic Clinical Decision Support System (CDSS) that encompasses the concept of the "Clinical Mendeliome" as a patient-centric list of genomic variants that are clinically actionable and introduces the concept of the "Archival Value Criterion" as a decision-making formalism that approximates the cost-effectiveness of capturing, storing, and curating genome-scale sequencing data. We describe a prototype Genomic CDSS that we developed as a first step toward implementation of the framework. CONCLUSION: The proposed framework and prototype solution are designed to address the perspectives of stakeholders, stimulate effective clinical use of genomic data, drive genomic research, and meet current and future needs. The framework also can be broadly applied to additional fields, including other '-omics' fields. We advocate for the creation of a Task Force on the Clinical Mendeliome, charged with defining Clinical Mendeliomes and drafting clinical guidelines for their use. PMID- 27195308 TI - Developing an Algorithm to Identify History of Cancer Using Electronic Medical Records. AB - INTRODUCTION/OBJECTIVE: The objective of this study was to develop an algorithm to identify Kaiser Permanente Colorado (KPCO) members with a history of cancer. BACKGROUND: Tumor registries are used with high precision to identify incident cancer, but are not designed to capture prevalent cancer within a population. We sought to identify a cohort of adults with no history of cancer, and thus, we could not rely solely on the tumor registry. METHODS: We included all KPCO members between the ages of 40-75 years who were continuously enrolled during 2013 (N=201,787). Data from the tumor registry, chemotherapy files, inpatient and outpatient claims were used to create an algorithm to identify members with a high likelihood of cancer. We validated the algorithm using chart review and calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for occurrence of cancer. FINDINGS: The final version of the algorithm achieved a sensitivity of 100 percent and specificity of 84.6 percent for identifying cancer. If we relied on the tumor registry alone, 47 percent of those with a history of cancer would have been missed. DISCUSSION: Using the tumor registry alone to identify a cohort of patients with prior cancer is not sufficient. In the final version of the algorithm, the sensitivity and PPV were improved when a diagnosis code for cancer was required to accompany oncology visits or chemotherapy administration. CONCLUSION: Electronic medical record (EMR) data can be used effectively in combination with data from the tumor registry to identify health plan members with a history of cancer. PMID- 27195310 TI - Restoration of Degraded Soil in the Nanmangalam Reserve Forest with Native Tree Species: Effect of Indigenous Plant Growth-Promoting Bacteria. AB - Restoration of a highly degraded forest, which had lost its natural capacity for regeneration, was attempted in the Nanmangalam Reserve Forest in Eastern Ghats of India. In field experiment, 12 native tree species were planted. The restoration included inoculation with a consortium of 5 native plant growth-promoting bacteria (PGPB), with the addition of small amounts of compost and a chemical fertilizer (NPK). The experimental fields were maintained for 1080 days. The growth and biomass varied depending on the plant species. All native plants responded well to the supplementation with the native PGPB. The plants such as Pongamia pinnata, Tamarindus indica, Gmelina arborea, Wrightia tinctoria, Syzygium cumini, Albizia lebbeck, Terminalia bellirica, and Azadirachta indica performed well in the native soil. This study demonstrated, by using native trees and PGPB, a possibility to restore the degraded forest. PMID- 27195309 TI - Preparing for the ICD-10-CM Transition: Automated Methods for Translating ICD Codes in Clinical Phenotype Definitions. AB - BACKGROUND: The national mandate for health systems to transition from ICD-9-CM to ICD-10-CM in October 2015 has an impact on research activities. Clinical phenotypes defined by ICD-9-CM codes need to be converted to ICD-10-CM, which has nearly four times more codes and a very different structure than ICD-9-CM. METHODS: We used the Centers for Medicare & Medicaid Services (CMS) General Equivalent Maps (GEMs) to translate, using four different methods, condition specific ICD-9-CM code sets used for pragmatic trials (n=32) into ICD-10-CM. We calculated the recall, precision, and F score of each method. We also used the ICD-9-CM and ICD-10-CM value sets defined for electronic quality measure as an additional evaluation of the mapping methods. RESULTS: The forward-backward mapping (FBM) method had higher precision, recall and F-score metrics than simple forward mapping (SFM). The more aggressive secondary (SM) and tertiary mapping (TM) methods resulted in higher recall but lower precision. For clinical phenotype definition, FBM was the best (F=0.67), but was close to SM (F=0.62) and TM (F=0.60), judging on the F-scores alone. The overall difference between the four methods was statistically significant (one-way ANOVA, F=5.749, p=0.001). However, pairwise comparisons between FBM, SM, and TM did not reach statistical significance. A similar trend was found for the quality measure value sets. DISCUSSION: The optimal method for using the GEMs depends on the relative importance of recall versus precision for a given use case. It appears that for clinically distinct and homogenous conditions, the recall of FBM is sufficient. The performance of all mapping methods was lower for heterogeneous conditions. Since code sets used for phenotype definition and quality measurement can be very similar, there is a possibility of cross-fertilization between the two activities. CONCLUSION: Different mapping approaches yield different collections of ICD-10-CM codes. All methods require some level of human validation. PMID- 27195311 TI - Automated Identification of Abnormal Adult EEGs. AB - The interpretation of electroencephalograms (EEGs) is a process that is still dependent on the subjective analysis of the examiners. Though interrater agreement on critical events such as seizures is high, it is much lower on subtler events (e.g., when there are benign variants). The process used by an expert to interpret an EEG is quite subjective and hard to replicate by machine. The performance of machine learning technology is far from human performance. We have been developing an interpretation system, AutoEEG, with a goal of exceeding human performance on this task. In this work, we are focusing on one of the early decisions made in this process - whether an EEG is normal or abnormal. We explore two baseline classification algorithms: k-Nearest Neighbor (kNN) and Random Forest Ensemble Learning (RF). A subset of the TUH EEG Corpus was used to evaluate performance. Principal Components Analysis (PCA) was used to reduce the dimensionality of the data. kNN achieved a 41.8% detection error rate while RF achieved an error rate of 31.7%. These error rates are significantly lower than those obtained by random guessing based on priors (49.5%). The majority of the errors were related to misclassification of normal EEGs. PMID- 27195313 TI - Expanding indications in robotic upper renal tract surgery: The sky's the limit. PMID- 27195312 TI - Proteomics analysis reveals a Th17-prone cell population in presymptomatic graft versus-host disease. AB - Gastrointestinal graft-versus-host-disease (GI-GVHD) is a life-threatening complication occurring after allogeneic hematopoietic cell transplantation (HCT), and a blood biomarker that permits stratification of HCT patients according to their risk of developing GI-GVHD would greatly aid treatment planning. Through in depth, large-scale proteomic profiling of presymptomatic samples, we identified a T cell population expressing both CD146, a cell adhesion molecule, and CCR5, a chemokine receptor that is upregulated as early as 14 days after transplantation in patients who develop GI-GVHD. The CD4+CD146+CCR5+ T cell population is Th17 prone and increased by ICOS stimulation. shRNA knockdown of CD146 in T cells reduced their transmigration through endothelial cells, and maraviroc, a CCR5 inhibitor, reduced chemotaxis of the CD4+CD146+CCR5+ T cell population toward CCL14. Mice that received CD146 shRNA-transduced human T cells did not lose weight, showed better survival, and had fewer CD4+CD146+CCR5+ T cells and less pathogenic Th17 infiltration in the intestine, even compared with mice receiving maraviroc with control shRNA- transduced human T cells. Furthermore, the frequency of CD4+CD146+CCR5+ Tregs was increased in GI-GVHD patients, and these cells showed increased plasticity toward Th17 upon ICOS stimulation. Our findings can be applied to early risk stratification, as well as specific preventative therapeutic strategies following HCT. PMID- 27195314 TI - Potential role for metformin in urologic oncology. AB - Metformin is one of the most commonly used drugs worldwide. It is currently considered first-line pharmacological agent for management of diabetes mellitus type 2. Recent studies have suggested that metformin may have further benefits, especially in the field of urologic oncology. Use of metformin has been shown to be associated with decreased incidence and improved outcomes of prostate, bladder, and kidney cancer. These studies suggest that metformin does have a future role in the prevention and management of urologic malignancies. In this review, we will discuss the latest findings in this field and its implications on the management of urologic oncology patients. PMID- 27195317 TI - The histologic features of intratubular germ cell neoplasia and its correlation with tumor behavior. AB - PURPOSE: To assess the prevalence of intratubular germ cell neoplasia (ITGCN) in patients with concurrent testis tumor and its correlation with histologic features and serum tumor markers. MATERIALS AND METHODS: From 2003 to 2015, 179 patients underwent radical orchiectomy due to testicular mass. Tissue specimens were evaluated by an expert uro-pathologist using immunohistochemistry (IHC) staining, in addition to light microscopy, to identify presence of ITGCN. Patients' demographic characteristics, histologic subtypes, pathologic stage of tumor and serum tumor markers were gathered and analyzed. RESULTS: Eighty-five out of 179 patients (47.5%) had concomitant ITGCN according to IHC staining. There was not statistically significant difference in histologic type, histologic components, cryptorchidism, and lymphovascular invasion between the 2 groups (p=0.151, p=0.11, p=0.233, p=0.413, and p=0.14, respectively). The prevalence of ITGCN was significantly higher in patients with stage T2 and T3 of tumor than those with stage T1. Elevated serum alpha feto protein level is much common in patients with ITGCN (p<0.001). CONCLUSIONS: The prevalence of concurrent ITGCN in our region is lower than previous data from western countries. ITGCN is more common in higher tumor stages and is accompanied with elevated serum alpha feto protein levels before surgery. Presence of ITGCN in adjacent tissue may suggest a negative cancer behavior. PMID- 27195316 TI - The PREVAIL trial of enzalutamide in men with chemotherapy-naive, metastatic castration-resistant prostate cancer: Post hoc analysis of Korean patients. AB - PURPOSE: This post hoc analysis evaluated treatment effects, safety, and pharmacokinetics of enzalutamide in Korean patients in the phase 3, double-blind, placebo-controlled PREVAIL trial. MATERIALS AND METHODS: Asymptomatic or mildly symptomatic chemotherapy-naive men with metastatic castration-resistant prostate cancer that progressed on androgen deprivation therapy received 160 mg/d oral enzalutamide or placebo (1:1) until death or discontinuation due to radiographic progression or skeletal-related event and initiation of subsequent therapy. Coprimary end points were centrally assessed radiographic progression-free survival (rPFS) and overall survival (OS). Secondary end points included investigator-assessed rPFS, time to initiation of chemotherapy, time to prostate specific antigen (PSA) progression, PSA response (>=50% decline), and time to skeletal-related event. RESULTS: Of 1,717 total patients, 78 patients were enrolled in Korea (enzalutamide, n=40; placebo, n=38). Hazard ratios (95% confidence interval) for enzalutamide versus placebo were 0.23 (0.02-2.24) for centrally assessed rPFS, 0.77 (0.28-2.15) for OS, 0.21 (0.08-0.51) for time to chemotherapy, and 0.31 (0.17-0.56) for time to PSA progression. A PSA response was observed in 70.0% of enzalutamide-treated and 10.5% of placebo-treated Korean patients. Adverse events of grade >=3 occurred in 33% of enzalutamide-treated and 11% of placebo-treated Korean patients, with median treatment durations of 13.0 and 5.1 months, respectively. At 13 weeks, the plasma concentration of enzalutamide plus N-desmethyl enzalutamide was similar in Korean and non-Korean patients (geometric mean ratio, 1.04; 90% confidence interval, 0.97-1.10). CONCLUSIONS: In Korean patients, treatment effects and safety of enzalutamide were consistent with those observed in the overall PREVAIL study population (ClinicalTrials.gov Identifier: NCT01212991). PMID- 27195315 TI - Nocturia: The circadian voiding disorder. AB - Nocturia is a prevalent condition of waking to void during the night. The concept of nocturia has evolved from being a symptomatic aspect of disease associated with the prostate or bladder to a form of lower urinary tract disorder. However, recent advances in circadian biology and sleep science suggest that it might be important to consider nocturia as a form of circadian dysfunction. In the current review, nocturia is reexamined with an introduction to sleep disorders and recent findings in circadian biology in an attempt to highlight the importance of rediscovering nocturia as a problem of chronobiology. PMID- 27195318 TI - Electronic nutritional intake assessment in patients with urolithiasis: A decision impact analysis. AB - PURPOSE: To evaluate a physician's impression of a urinary stone patient's dietary intake and whether it was dependent on the medium through which the nutritional data were obtained. Furthermore, we sought to determine if using an electronic food frequency questionnaire (FFQ) impacted dietary recommendations for these patients. MATERIALS AND METHODS: Seventy-six patients attended the Stone Clinic over a period of 6 weeks. Seventy-five gave consent for enrollment in our study. Patients completed an office-based interview with a fellowship trained endourologist, and a FFQ administered on an iPad. The FFQ assessed intake of various dietary components related to stone development, such as oxalate and calcium. The urologists were blinded to the identity of patients' FFQ results. Based on the office-based interview and the FFQ results, the urologists provided separate assessments of the impact of nutrition and hydration on the patient's stone disease (nutrition impact score and hydration impact score, respectively) and treatment recommendations. Multivariate logistic regressions were used to compare pre-FFQ data to post-FFQ data. RESULTS: Higher FFQ scores for sodium (odds ratio [OR], 1.02; p=0.02) and fluids (OR, 1.03, p=0.04) were associated with a higher nutritional impact score. None of the FFQ parameters impacted hydration impact score. A higher FFQ score for oxalate (OR, 1.07; p=0.02) was associated with the addition of at least one treatment recommendation. CONCLUSIONS: Information derived from a FFQ can yield a significant impact on a physician's assessment of stone risks and decision for management of stone disease. PMID- 27195319 TI - Diversity of patient profile, urethral stricture, and other disease manifestations in a cohort of adult men with lichen sclerosus. AB - PURPOSE: Lichen sclerosus (LS) in men is poorly understood. Though uncommon, it is often severe and leads to repeated surgical interventions and deterioration in quality of life. We highlight variability in disease presentation, diagnosis, and patient factors in male LS patients evaluated at a tertiary care center. MATERIALS AND METHODS: We retrospectively reviewed charts of male patients presenting to our reconstructive urology clinic with clinical or pathologic diagnosis of LS between 2004 and 2014. Relevant clinical and demographic information was abstracted and descriptive statistics calculated. Subgroup comparisons were made based on body mass index (BMI), urethral stricture, and pathologic confirmation of disease. RESULTS: We identified 94 patients with clinical diagnosis of LS. Seventy percent (70%) of patients in this cohort had BMI >30 kg/m(2), and average age was 51.5 years. Lower BMI patients were more likely to suffer from urethral stricture disease compared to overweight counterparts (p=0.037). Patients presenting with stricture disease were more likely to be younger (p=0.003). Thirty percent (30%) of this cohort had a pathologic diagnosis of LS. CONCLUSIONS: Urethral stricture is the most common presentation for men with LS. Many patients endure skin scarring and have numerous comorbidities. Patient profile is diverse, raising the concern that not all patients with clinical diagnosis of LS are suffering from identical disease processes. The rate of pathologic confirmation at a tertiary care institution is alarmingly low. Our findings support a role for increased focus on pathologic confirmation and further delineation of the subtype of disease based on location and clinical manifestations. PMID- 27195320 TI - Laparoendoscopic single-site simple nephrectomy using a magnetic anchoring system in a porcine model. AB - PURPOSE: Magnetic anchoring devices may reduce the number of port sites needed in laparoscopic surgery. In this study, we prospectively assessed the feasibility of using a magnetic anchoring and guidance system (MAGS) in laparoendoscopic single site (LESS) surgery performed by novices. MATERIALS AND METHODS: A total of 10 LESS simple nephrectomies were performed with or without MAGS in a nonsurvival porcine model by 6 operators with no previous LESS surgery experience. After installation of the homemade single port, an intra-abdominal magnet was fixed to the renal parenchyma with suturing and stabilized by an external magnet placed on the flank so that the position of the kidney could be easily changed by moving the external handheld magnet. The length of the procedure and any intraoperative complications were evaluated. RESULTS: Operative time (mean+/-standard deviation) was shorter in the group using the magnetic anchoring device (M-LESS-N) than in the group with conventional LESS nephrectomy (C-LESS-N) (63+/-20.8 minutes vs. 82+/-40.7 minutes, respectively). Although all nephrectomies were completed uneventfully in the M-LESS-N group, renal vein injury occurred during dissection of the renal hilum in two cases of C-LESS-N and was resolved by simultaneous transection of the renal artery and vein with an Endo-GIA stapler. CONCLUSIONS: LESS-N using MAGS is a feasible technique for surgeons with no LESS surgery experience. Taking into account the 2 cases of renal vein injury in the C-LESS-N group, the application of MAGS may be beneficial for overcoming the learning curve of LESS surgery. PMID- 27195323 TI - [Differential diagnosis of focal osteoplastic masses in the lung of miners]. AB - The paper reviews literature on the current aspects of the diagnosis and expert appraisal of focal osteoplastic masses in the lung upon dust exposure to dust factors. It considers different aspects of the pathogenesis of osteoplastic changes in the tissue structural elements of pulmonary histione. Current views on the prevalence, etiology, and pathogenesis, as well as morphological changes in the development of this abnormality, its association with the dust damaging effects of human activities are reflected. PMID- 27195322 TI - Robot-assisted partial cystectomy with intraoperative frozen section examination: Evolution and evaluation of a novel technique. AB - PURPOSE: To describe a novel modification to robot-assisted partial cystectomy (RAPC) that allows for intraoperative surgical margin assessment by bimanual examination and frozen-section analysis. MATERIALS AND METHODS: A total of 7 patients underwent RAPC at a single tertiary-care institution between 2008 and 2013. The technique evolved over the study-period and permitted real-time intraoperative surgical margin evaluation in the last 5 patients via bimanual examination and frozen-section analysis, utilizing the GelPOINT platform (a hand assist device). The GelPOINT platform was placed through a 4- to 5-cm vertical supraumbilical incision and allowed for rapid retrieval of the bladder specimen without compromising the pneumoperitoneum or prolonging the operative time. Perioperative, oncological and functional outcomes were evaluated; all patients had a minimum 12-month follow-up. At the time of last follow-up, a cross sectional survey of patients was performed to evaluate regret/satisfaction utilizing validated questionnaires. RESULTS: The mean age was 72.5 years; 71.4% of the patients were men (n=5). All patients underwent RAPC for a malignant indication. The mean operative and console times were 291 and 217 minutes, respectively. No patient had a positive surgical margin. Mean length-of-stay was 1.7 days. At a median follow-up of 38.9 months, 1 patient experienced a local recurrence 6 months postsurgery. The only mortality was secondary to Lewy-body disease, in the same patient, 1 year postoperatively. Patient assessment of regret and satisfaction indicated 0% regret and 0% dissatisfaction. CONCLUSIONS: The 'modified' technique of RAPC is technically feasible, safe, and reproducible; further, RAPC leads to favorable oncological, functional and quality-of-life outcomes in patients eligible for partial cystectomy. PMID- 27195321 TI - Light-controlled relaxation of the rat penile corpus cavernosum using NOBL-1, a novel nitric oxide releaser. AB - PURPOSE: To investigate whether relaxation of the rat penile corpus cavernosum could be controlled with NOBL-1, a novel, light-controllable nitric oxide (NO) releaser. MATERIALS AND METHODS: Fifteen-week-old male Wistar-ST rats were used. The penile corpus cavernosum was prepared and used in an isometric tension study. After noradrenaline (10(-5) M) achieved precontraction, the penile corpus cavernosum was irradiated by light (470-500 nm) with and without NOBL-1 (10(-6) M). In addition, we noted rats' responses to light with vardenafil (10(-6) M), a phosphodiesterase-5 (PDE-5) inhibitor. Next, responses to light in the presence of a guanylate cyclase inhibitor, ODQ (1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1 one) (10(-5) M), were measured. All measurements were performed in pretreated L NAME (10(-4) M) conditions to inhibit endogenous NO production. RESULTS: Corpus cavernosal smooth muscle, precontracted with noradrenaline, was unchanged by light irradiation in the absence of NOBL-1. However, in the presence of NOBL-1, corpus cavernosal smooth muscle, precontracted with noradrenaline, relaxed in response to light irradiation. After blue light irradiation ceased, tension returned. In addition, the light response was obviously enhanced in the presence of a PDE-5 inhibitor. CONCLUSIONS: This study showed that rat corpus cavernosal smooth muscle relaxation can be light-controlled using NOBL-1, a novel, light sensitive NO releaser. Though further in vivo studies are needed to investigate possible usefulness, NOBL-1 may be prove to be a useful tool for erectile dysfunction therapy, specifically in the field of penile rehabilitation. PMID- 27195324 TI - [Preclinical and clinical trials of the new tuberculosis drug perchlozon]. AB - The paper sets forth the stages of design and introduction of the new Russian tuberculosis (TB) drug perchlozon registered in the Russian Federation in 2012. Based on the results of Phases I-III clinical trials, the authors evaluate the efficacy and safety of the agent and consider the adverse effects of its treatment for respiratory TB. The use of perchlozon as a component of combination therapy versus standard chemotherapy regimens significantly reduces abacillation time in pulmonary TB caused by its drug-resistant pathogen. In terms of the higher prevalence of TB induced by its pathogen resistant to many drugs (with multiple and broad-spectrum drug resistance), perchlozon is an essential drug that has antituberculous activity mainly against multidrug-resistant Mycobacterium tuberculosis strains and gives patients with the severest and epidemiologically poor form of TB the chance to recover. PMID- 27195325 TI - [Not Available]. PMID- 27195326 TI - [Not Available]. PMID- 27195327 TI - [Not Available]. PMID- 27195328 TI - [Not Available]. PMID- 27195329 TI - Informed consent practices by junior medical officers: a cross-sectional study. PMID- 27195331 TI - Medicine in small doses. Recognizing and managing psychological stress and under performance in interns. PMID- 27195330 TI - A case of multiple myeloma mimics: extensive bone metastasis of hepatocellular carcinoma without liver mass. PMID- 27195332 TI - Hemophagocytosis in a patient with sickle cell disease. PMID- 27195333 TI - In Memoriam Nigel C. Veitch, January 26th 1965-September 1st 2014. PMID- 27195334 TI - Retraction notice to microarray analysis of microRNA expression in liver cancer tissues and normal control [GENE 523/2 (2014) 158-60]. PMID- 27195335 TI - Retraction notice to candidate agents for pancreatic ductal adenocarcinoma identified by a sub-pathway based method [GENE 540/2 (2014) 232-7]. PMID- 27195336 TI - Retraction notice to protein-protein interaction and SNP analysis in intraductal papillary mucinous neoplasm [GENE 513/1 (2013) 219-24]. PMID- 27195337 TI - Revised Success Criteria: A Vision to Meet Frailty and Dependency in Implant Patients. PMID- 27195338 TI - SGR Out, MACRA In. PMID- 27195339 TI - SIREN to Replace NETT and ROC. PMID- 27195341 TI - Special Issue on Neurodynamic Systems for Optimization and Applications. PMID- 27195342 TI - Fatalities in Traffic Crashes Involving All-Terrain Vehicles. PMID- 27195343 TI - The Jedi Dark Side of Implant Therapy? Peri-implant Disease(s): Recent Updates on Prevalence and Etiology. PMID- 27195344 TI - Steven G Holtzman: The blending of professional and personal lives. PMID- 27195382 TI - Supramalleolar Osteotomies for the Treatment of Ankle Arthritis. AB - Supramalleolar osteotomy is a joint-preserving surgical treatment for patients with asymmetric valgus or varus ankle arthritis. The primary goal of the procedure is to realign the spatial relationship between the talus and tibia and thereby normalize joint loading within the ankle. Procedures to balance the soft tissues, as well as hindfoot osteotomy and arthrodesis, may also be necessary. Clinical studies of supramalleolar osteotomy demonstrate that correction of the altered biomechanics associated with asymmetric arthritis improves functional outcomes. PMID- 27195383 TI - Medical Device Regulation: A Comparison of the United States and the European Union. AB - Medical device regulation is a controversial topic in both the United States and the European Union. Many physicians and innovators in the United States cite a restrictive US FDA regulatory process as the reason for earlier and more rapid clinical advances in Europe. The FDA approval process mandates that a device be proved efficacious compared with a control or be substantially equivalent to a predicate device, whereas the European Union approval process mandates that the device perform its intended function. Stringent, peer-reviewed safety data have not been reported. However, after recent high-profile device failures, political pressure in both the United States and the European Union has favored more restrictive approval processes. Substantial reforms of the European Union process within the next 5 to 10 years will result in a more stringent approach to device regulation, similar to that of the FDA. Changes in the FDA regulatory process have been suggested but are not imminent. PMID- 27195385 TI - Examining Quality Management Audits in Nuclear Medicine Practice as a lifelong learning process: opportunities and challenges to the nuclear medicine professional and beyond. AB - This essay will explore the critical issues and challenges surrounding lifelong learning for professionals, initially exploring within the profession and organizational context of nuclear medicine practice. It will critically examine how the peer-review process called Quality Management Audits in Nuclear Medicine Practice (QUANUM) of the International Atomic Energy Agency (IAEA) can be considered a lifelong learning opportunity to instill a culture of quality to improve patient care and elevate the status of the nuclear medicine profession and practice within the demands of social changes, policy, and globalization. This will be explored initially by providing contextual background to the identity of the IAEA as an organization responsible for nuclear medicine professionals, followed by the benefits that QUANUM can offer. Further key debates surrounding lifelong learning, such as compulsification of lifelong learning and impact on professional change, will then be weaved through the discussion using theoretical grounding through a qualitative review of the literature. Keeping in mind that there is very limited literature focusing on the implications of QUANUM as a lifelong learning process for nuclear medicine professionals, this essay uses select narratives and observations of QUANUM as a lifelong learning process from an auditor's perspective and will further provide a comparative perspective of QUANUM on the basis of other lifelong learning opportunities such as continuing professional development activities and observe parallelisms on its benefits and challenges that it will offer to other professionals in other medical speciality fields and in the teaching profession. PMID- 27195384 TI - The progressive role of acoustic cavitation for non-invasive therapies, contrast imaging and blood-tumor permeability enhancement. AB - INTRODUCTION: Drug delivery pertaining to acoustic cavitation generated from ultrasonic (US) irradiation is advantageous for devising smarter and more advanced therapeutics. The aim is to showcase microbubbles as drug carriers and robust theranostic for non-invasive therapies across diverse biomedical disciplines, highlighting recent technologies in this field for overcoming the blood-brain barrier (BBB) to treat cancers and neurological disorders. AREAS COVERED: This article reviews work on the optimized tuning of ultrasonic parameters, sonoporation, transdermal and responsive drug delivery, acoustic cavitation in vasculature and oncology, contrast imaging for real-time magnification of cell-microbubble dynamics and biomolecular targeting. Scholarly literature was sought through database search on key terminology, latest topics, reputable experts and established journals over the last five years. EXPERT OPINION: Cavitation offers immense promise in overcoming current diffusion and convection limitations for treating skull/brain/vascular/tissue injuries and ablating tumors to minimize chronic/acute effects. Since stable cavitation facilitates the restoration of US-opened BBB and the modulation of drug concentration, US equipment with programmable imaging modality and sensitivity are envisaged to create safer miniaturized devices for personalized care. Due to differing biomedical protocols with regard to specific medical conditions, quantitative and qualitative controls are mandatory before translation to real life clinical applications can be accomplished. PMID- 27195423 TI - Pre-existing diabetes and lung cancer prognosis. AB - BACKGROUND: The aims of this study are to investigate the impact of pre-existing diabetes and diabetes treatments on lung cancer prognosis. METHODS: A total of 2484 women with confirmed incident lung cancer from the Women's Health Initiative were followed for an average of 2.9 years through the date of death or 29 August 2014. RESULTS: Compared with women with lung cancer but without diabetes, women with lung cancer and diabetes had significantly increased risk of overall mortality (HR=1.27, 95% CI: 1.07-1.50). Women with diabetes receiving insulin or metformin or women who had long duration of diabetes also had increased risk of overall mortality. CONCLUSIONS: Our large prospective study provides evidence that pre-existing diabetes is associated with poor overall survival among women with lung cancer, but do not support the hypothesis that metformin use may have a protective effect in women with lung cancer and diabetes. PMID- 27195425 TI - The effects of nanoparticles on the renal system. AB - Through a process of translocation across biological barriers, nanoparticles can reach and deposit in secondary target organs where they may induce adverse biological reactions. Therefore, a correct assessment of nanoparticle-induced adverse effects should take into account the different aspects of toxicokinetics and tissues that may be targeted by nanoparticles. For this reason, a comprehensive evaluation of renal nanotoxicity is urgently needed as kidneys are particularly susceptible to xenobiotics and renal excretion is an expected and possible elimination route of nanoparticles in living organisms. On one hand, summarizing the findings of in vitro and in vivo studies that have investigated the adverse effects of nanoparticles on the kidney, this review intends to provide a thorough insight into the nephrotoxicity of these substances. The evaluation of the in vitro studies revealed that different types of nanoparticles (carbon, metal and/or silica nanoparticles) are able to exert significant cytotoxic effects (i.e., decreased cell viability, induction of oxidative stress, mitochondrial or cytoskeleton dysfunction and cell membrane and DNA damage). On the other hand, in vivo studies demonstrated that nanoparticles exhibited an important nephrotoxic potential both at tubular (i.e., degeneration of tubular epithelial cell, cellular fragments and proteinaceous liquid in tubule lumen, renal interstitial fibrosis) and glomerular level (i.e., swollen glomeruli, changes in Bowman's space and proliferation of mesangial cells). Although the data currently available indicate that nanoparticles may adversely impact the renal system, further studies are needed in order to clarify all the potential molecular mechanisms of nephrotoxicity induced by these xenobiotics, in particular at glomerular level. PMID- 27195424 TI - Clinical impact and network of determinants of tumour necrosis in colorectal cancer. AB - BACKGROUND: The disease outcome in colorectal cancer (CRC) can vary in a wide range within the same tumour stage. The aim of this study was to clarify the prognostic value and the determinants of tumour necrosis in CRC. METHODS: The areal proportion (%) of tumour tissue showing coagulative necrosis was evaluated in a cohort of 147 CRC patients and correlated with basic clinicopathological characteristics, microvascular density (MVD), cell proliferation rate, KRAS and BRAF mutations, and survival. To validate the prognostic significance of tumour necrosis, an independent cohort of 418 CRC patients was analysed. RESULTS: Tumour necrosis positively correlated with tumour stage (P=8.5E-4)-especially with T class (4.0E-6)-and inversely correlated with serrated histology (P=0.014), but did not significantly associate with cell proliferation rate, MVD, and KRAS or BRAF mutation. Abundant (10% or more) tumour necrosis associated with worse disease-free survival independent of stage and other biological or clinicopathological characteristics in both cohorts, and the adverse effect was directly related to its extent. High CD105 MVD was also a stage independent marker for worse disease-free survival. CONCLUSIONS: Tumour necrosis percentage is a relevant histomorphological prognostic indicator in CRC. More studies are needed to disclose the mechanisms of tumour necrosis. PMID- 27195426 TI - A Central Cysteine Residue Is Essential for the Thermal Stability and Function of SUMO-1 Protein and SUMO-1 Peptide-Protein Conjugates. AB - SUMOylation constitutes a major post-translational modification (PTM) used by the eukaryote cellular machinery to modulate protein interactions of the targeted proteins. The small ubiquitin-like modifier-1 (SUMO-1) features a central and conserved cysteine residue (Cys52) that is located in the hydrophobic core of the protein and in tight contact with Phe65, suggesting the occurrence of an S/pi interaction. To investigate the importance of Cys52 on SUMO-1 thermal stability and biochemical properties, we produced by total chemical synthesis SUMO-1 or SUMO-1 Cys52Ala peptide-protein conjugates featuring a native isopeptidic bond between SUMO-1 and a peptide derived from p53 tumor suppressor protein. The Cys52Ala modification perturbed SUMO-1 secondary structure and resulted in a dramatic loss of protein thermal stability. Moreover, the cleavage of the isopeptidic bond by the deconjugating enzyme Upl1 was significantly less efficient than for the wild-type conjugate. Similarly, the in vitro SUMOylation of RanGap1 by E1/E2 conjugating enzymes was significantly less efficient with the SUMO-1 C52A analog compared to wild-type SUMO-1. These data demonstrate the critical role of Cys52 in maintaining SUMO-1 conformation and function and the importance of keeping this cysteine intact for the study of SUMO-1 protein conjugates. PMID- 27195427 TI - Structural Understanding of Superior Battery Properties of Partially Ni-Doped Li2MnO3 as Cathode Material. AB - We examined the crystal structures of Li2(NixMn1-x)O3(-delta) (x = 0, 1/10, 1/6, and 1/4) to elucidate the relationship between the structure and electrochemical performance of the compounds using neutron and synchrotron X-ray powder diffraction analyses in combination. Our examination revealed that these crystals contain a large number of stacking faults and exhibit significant cation mixing in the transition-metal layers; the cation mixing becomes significant with an increase in the Ni concentration. Charge-discharge measurements showed that the replacement of Mn with Ni lowers the potential of the charge plateau and leads to higher charge-discharge capacities. From a topological point of view with regard to the atomic arrangement in the crystals, it is concluded that substituting Mn in Li2MnO3 with Ni promotes the formation of smooth Li percolation paths, thus increasing the number of active Li ions and improving the charge-discharge capacity. PMID- 27195428 TI - Insights into the use of gadolinium and gadolinium/boron-based agents in imaging guided neutron capture therapy applications. AB - Gadolinium neutron capture therapy (Gd-NCT) is currently under development as an alternative approach for cancer therapy. All of the clinical experience to date with NCT is done with (10)B, known as boron neutron capture therapy (BNCT), a binary treatment combining neutron irradiation with the delivery of boron containing compounds to tumors. Currently, the use of Gd for NCT has been getting more attention because of its highest neutron cross-section. Although Gd-NCT was first proposed many years ago, its development has suffered due to lack of appropriate tumor-selective Gd agents. This review aims to highlight the recent advances for the design, synthesis and biological testing of new Gd- and B-Gd containing compounds with the task of finding the best systems able to improve the NCT clinical outcome. PMID- 27195430 TI - Infected Donor Biomass and Active Feeding Increase Waterborne Transmission of Ichthyophonus sp. to Rainbow Trout Sentinels. AB - The precise nature of Ichthyophonus sp. transmission among wild fishes has eluded description for over a century. Transmission among piscivores is direct, via ingestion of infected prey, but there is also evidence for waterborne transmission between infected and uninfected individuals. Transmission among planktivores is believed to be via a waterborne infectious cell, but definitive proof of this mechanism has not been forthcoming. To explore possible mechanisms of transmission we used Rainbow Trout Oncorhynchus mykiss as a model system and examined the consequence of housing infected donor fish with uninfected (sentinel) fish, without physical contact. We examined two variables linked to transmission: (1) feeding and nonfeeding sentinel fish, and (2) biomass of infected donor fish. Specific-pathogen free sentinel trout were placed in fine mesh baskets suspended in tanks containing varying numbers of larger Ichthyophonus-infected donor fish and held for 10 weeks, during which time they were examined by in vitro explant culture for the presence of Ichthyophonus. Treatment groups consisted of fed and unfed sentinels housed with infected donors of increasing biomass. After 10 weeks infection prevalence in fed sentinels was significantly higher than in unfed sentinels, and Ichthyophonus was detected earlier in fed fish than in unfed fish. There was no correlation between infection prevalence and donor biomass in fed sentinels, but there was a strong correlation between infection prevalence and increasing donor biomass in unfed sentinels. These data suggest that Ichthyophonus is maintained in wild fish populations by two distinct mechanisms: (1) waterborne infectious cells ingested directly from the water by planktivores, and (2) both infected prey and waterborne infectious cells ingested by piscivores. Received November 13, 2015; accepted February 13, 2016. PMID- 27195431 TI - Hands-free: A Low-Cost Adapter for Smartphone Microscopic Photography Using a Cardboard Toilet-Paper Roll. PMID- 27195429 TI - The effect of urea and taurine as hydrophilic penetration enhancers on stratum corneum lipid models. AB - To optimize transdermal application of drugs, the barrier function of the skin, especially the stratum corneum (SC), needs to be reduced reversibly. For this purpose, penetration enhancers like urea or taurine are applied. Until now, it is unclear if this penetration enhancement is caused by an interaction with the SC lipid matrix or related to effects within the corneocytes. Therefore, the effects of both hydrophilic enhancers on SC models with different dimensionality, ranging from monolayers to multilayers, have been investigated in this study. Many sophisticated methods were applied to ascertain the mode of action of both substances on a molecular scale. The experiments reveal that there is no specific interaction when 10% urea or 5% taurine solutions are added to the SC model systems. No additional water uptake in the head group region and no decrease of the lipid chain packing density have been observed. Consequently, we suppose that the penetration enhancing effect of both substances might be based on the introduction of large amounts of water into the corneocytes, caused by the enormous water binding capacity of urea and a resulting osmotic pressure in case of taurine. PMID- 27195432 TI - Liquid Biopsy in Lung Cancer: A Perspective From Members of the Pulmonary Pathology Society. AB - Liquid biopsy has received extensive media coverage and has been called the holy grail of cancer detection. Attempts at circulating tumor cell and genetic material capture have been progressing for several years, and recent financially and technically feasible improvements of cell capture devices, plasma isolation techniques, and highly sensitive polymerase chain reaction- and sequencing-based methods have advanced the possibility of liquid biopsy of solid tumors. Although practical use of circulating RNA-based testing has been hindered by the need to fractionate blood to enrich for RNAs, the detection of circulating tumor cells has profited from advances in cell capture technology. In fact, the US Food and Drug Administration has approved one circulating tumor cell selection platform, the CellSearch System. Although the use of liquid biopsy in a patient population with a genomically defined solid tumor may potentially be clinically useful, it currently does not supersede conventional pretreatment tissue diagnosis of lung cancer. Liquid biopsy has not been validated for lung cancer diagnosis, and its lower sensitivity could lead to significant diagnostic delay if liquid biopsy were to be used in lieu of tissue biopsy. Ultimately, notwithstanding the enthusiasm encompassing liquid biopsy, its clinical utility remains unproven. PMID- 27195433 TI - Utilization of Cell-Transfer Technique for Molecular Testing on Hematoxylin-Eosin Stained Sections: A Viable Option for Small Biopsies That Lack Tumor Tissues in Paraffin Block. AB - CONTEXT: - In some instances the standard method of doing molecular testing from formalin-fixed, paraffin-embedded block is not possible because of limited tissue. Tumor cell-enriched cell-transfer technique has been proven useful for performing immunocytochemistry and molecular testing on cytologic smears. OBJECTIVE: - To establish the cell-transfer technique as a viable option for isolating tumor cells from hematoxylin-eosin (H&E)-stained slides. DESIGN: - Molecular testing was performed by using the cell-transfer technique on 97 archived H&E-stained slides from a variety of different tumors. Results were compared to the conventional method of molecular testing. RESULTS: - Polymerase chain reaction-based molecular testing via the cell-transfer technique was successfully performed on 82 of 97 samples (85%). This included 39 of 47 cases for EGFR, 10 of 11 cases for BRAF, and 33 of 39 cases for KRAS mutations. Eighty one of 82 cell-transfer technique samples (99%) showed agreement with previous standard method results, including 4 mutations and 35 wild-type alleles for EGFR, 4 mutations and 6 wild-type alleles for BRAF, and 11 mutations and 21 wild-type alleles for KRAS. There was only 1 discrepancy: a cell-transfer technique with a false-negative >KRAS result (wild type versus G12C). CONCLUSIONS: - Molecular testing performed on H&E-stained sections via cell-transfer technique is useful when tissue from cell blocks and small surgical biopsy samples is exhausted and the only available material for testing is on H&E-stained slides. PMID- 27195434 TI - Let's Have a Tweetup: The Case for Using Twitter Professionally. AB - Social media use is very common and can be an effective way for professionals to discuss information and interact with colleagues. Twitter (Twitter, Inc, San Francisco, California) is a social media network where posts, termed tweets, are limited to 140 characters. Professional use of Twitter is ideal for physicians interested in both networking and education and is optimally used to facilitate in-person networking. Live-tweeting (posting real-time reactions to events) at professional meetings is also a popular and highly successful use of Twitter. Physicians report patient privacy as the top concern preventing use of social media for professional reasons, and although generally social media use is safe, it is essential to understand how to protect patient confidentially. Other social media platforms with potential for professional use include Facebook (Facebook, Inc, Menlo Park, California), Instagram (Facebook, Inc), YouTube (YouTube, LLC, San Bruno, California), and Periscope (Twitter, Inc). With Twitter and other social media options, now is the time for pathologists to increase our visibility on social media and worldwide. PMID- 27195436 TI - Assessing depression in a geriatric cancer population. AB - OBJECTIVE: To examine the ability of three popular self-report measures of depression to assess depression in a geriatric cancer setting. METHOD: Cancer patients 70 years or older and on active treatment completed the Geriatric Depression Scale-Short Form, the Hospital Anxiety and Depression Scale, and the Center for Epidemiological Studies Depression Scale-Revised, and were interviewed using the depression module of the Structured Clinical Interview for DSM disorders (SCID) as the 'gold standard.' Analyses included calculating internal consistency, ROC curves, and the sensitivity and specificity to detect major depression (MDD) or minor depression (i.e. subthreshold depression). RESULTS: In a sample of 201 cancer patients (85% White; 64% completed college degree or higher), all three of the self-report measures produced adequate internal consistency and predicted depression greater than chance. However, the published cutoff scores for detecting MDD produced inadequate sensitivity, suggesting these scores will miss as many as 33%-83% of geriatric cancer patients who are depressed. Revised cutoff scores were lower than published cutoff scores. CONCLUSION: Although these measures produced good internal consistency and were better than chance at predicting depression in a geriatric cancer sample, the published cutoff scores for these measures did not perform well in predicting MDD nor minor depression. Of the three measures, the CES-D appeared to have the most utility. This data suggests that these popular screening measures may be inadequate for reliably identifying depression in a geriatric cancer population. Researchers and clinicians, therefore, should use caution when selecting depression measures for geriatric cancer patients and consider using the lower cut-off scores presented here. PMID- 27195435 TI - Population pharmacokinetics and prophylactic anti-emetic efficacy of ramosetron in surgical patients. AB - AIMS: This study characterized the pharmacokinetics of ramosetron and compared prophylactic anti-emetic efficacy with that of ondansetron in a large population. METHODS: Fifty-eight patients consented to the pharmacokinetic analysis and were assigned randomly to receive 0.3, 0.45 or 0.6 mg ramosetron after induction of anaesthesia. Blood samples were acquired at preset intervals. Non-compartmental and population pharmacokinetic analyses were performed. In total, 1102 patients consented to the evaluation of prophylactic anti-emetic efficacy and were allocated randomly to receive 0.3 mg ramosetron or 4 mg ondansetron at the end of surgery. An additional 16 mg ondansetron were mixed in the intravenous patient controlled analgesia pump of the ondansetron group. Post-operative nausea and vomiting (PONV) were evaluated 6, 24 and 48 h post-operatively using the Rhodes index of nausea, vomiting and retching (RINVR). Administration of rescue anti emetics and adverse events were evaluated. RESULTS: The pharmacokinetic parameter estimates were V1 (l) = 5.12, V2 (l) = 108, CL (l?min(-1) ) = 0.08 + (59?age(-1) ) * 0.09, Q (l?min(-1) ) = 1.42. The incidences of PONV in the ramosetron and ondansetron groups were 77 (13.9%) and 113 (20.6%) and 44 (7.9%) and 66 (12.0%) at 24 and 48 h post-operatively, respectively (P = 0.004, 0.030). RINVR was significantly lower in the ramosetron than the ondansetron group 24 and 48 h post operatively (P = 0.003, 0.025). Use of rescue anti-emetics and incidence of adverse events were comparable. CONCLUSIONS: A two compartment mammillary model was used to describe ramosetron pharmacokinetics. Prophylactic anti-emetic efficacy of ramosetron was significantly better 24 and 48 h post-operatively than that of ondansetron, particularly when the Apfel score was >= 3. PMID- 27195438 TI - Pretreatment MR Imaging Features of Triple-Negative Breast Cancer: Association with Response to Neoadjuvant Chemotherapy and Recurrence-Free Survival. AB - Purpose To investigate whether pretreatment breast magnetic resonance (MR) imaging features are associated with pathologic complete response (PCR) and recurrence-free survival after neoadjuvant chemotherapy (NAC) in patients with triple-negative breast cancer. Materials and Methods Identified were 132 patients with primary triple-negative breast cancers who underwent NAC and pretreatment MR imaging between 2004 and 2010. Three breast radiologists independently reviewed the MR images based on the 2013 Breast Imaging Reporting and Data System lexicon. Presence of intratumoral high signal intensity and peritumoral edema on T2 weighted images was also evaluated. Association of PCR and recurrence-free survival with MR imaging features was assessed by using logistic regression and Cox regression. Bonferroni correction was applied to the P values. Results Among 132 patients, 18 (14%) underwent PCR. Round or oval masses (odds ratio, 3.5 [95% confidence interval: 1.3, 9.7]; P = .02), the absence of intratumoral T2 high signal intensity (odds ratio, 3.8 [95% confidence interval: 1.3, 11.0]; P = .01), and the absence of peritumoral edema (odds ratio, 3.4 [95% confidence interval: 1.2, 9.5]; P = .02) were associated with PCR, but not significantly. After 54 months of median follow-up, there were 41 (31% [41 of 132]) breast cancer recurrences. Peritumoral edema was the only significant variable associated with worse recurrence-free survival (hazard ratio, 4.9 [95% confidence interval: 1.9, 12.6]; P = .001). Conclusion Pretreatment MR imaging features may be associated with PCR and recurrence-free survival in patients with triple-negative breast cancer. (c) RSNA, 2016 Online supplemental material is available for this article. PMID- 27195437 TI - Biochemical and Clinical Predictive Approach and Time Point Analysis of Hepatobiliary Phase Liver Enhancement on Gd-EOB-DTPA-enhanced MR Images: A Multicenter Study. AB - Purpose To identify biochemical factors associated with liver enhancement over time on gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced magnetic resonance (MR) images and predict the optimal time point of the hepatobiliary phase in various clinical settings. Materials and Methods This study was approved by the institutional review boards, and written informed consent was obtained from the 1903 patients enrolled. Simple and multiple logistic regression analyses were performed to investigate the biochemical factors associated with liver-to-spleen contrast (LSC) of at least 1.5 in the hepatobiliary phase. Changes in LSC and lesion-to-liver contrast (LLC) of lesions over time (at 5, 10, 15, and 20 minutes) were investigated with a linear mixed effects model in patients and lesions. For LSC, the optimal cutoff value was determined with receiver operating characteristic analysis of the most significant variable. Differences in LSC and LLC were analyzed in various clinical settings. Results Ultimately, 1870 patients were evaluated, as 33 were excluded according to study criteria. Prothrombin (PT) activity, total bilirubin level (P = .020), and total cholesterol level (P = .005) were significantly associated with LSC of at least 1.5 at 20 minutes, and PT activity was identified as the most significant factor (odds ratio, 1.271; 95% confidence interval: 1.109, 1.455; P = .001). LSC of at least 1.5 at 20 minutes with PT activity of at least 86.9% and less than 86.9% occurred in 555 of 626 patients (88.6%) and 388 of 575 patients (67.5%), respectively. Satisfactory liver enhancement at 20 minutes was significantly more likely to be achieved by patients with hepatitis B virus than by those with hepatitis C virus (P < .001) and by patients with metastasis than by those with hepatocellular carcinoma (P < .001). No significant difference in LLC was observed in patients examined at 1.5 and 3.0 T (P = .133). Conclusion Hepatic enhancement is significantly associated with PT activity, total bilirubin level, and total cholesterol level. PT activity of at least 86.9% could be used to shorten examination times at Gd-EOB-DTPA-enhanced MR imaging. (c) RSNA, 2016 Online supplemental material is available for this article. PMID- 27195440 TI - WITHDRAWN: Artichoke leaf extract for treating hypercholesterolaemia. PMID- 27195441 TI - Seawater Pervaporation through Zeolitic Imidazolate Framework Membranes: Atomistic Simulation Study. AB - An atomistic simulation study is reported for seawater pervaporation through five zeolitic imidazolate framework (ZIF) membranes including ZIF-8, -93, -95, -97, and -100. Salt rejection in the five ZIFs is predicted to be 100%. With the largest aperture, ZIF-100 possesses the highest water permeability of 5 * 10(-4) kg m/(m(2) h bar), which is substantially higher compared to commercial reverse osmosis membranes, as well as zeolite and graphene oxide pervaporation membranes. In ZIF-8, -93, -95, and -97 with similar aperture size, water flux is governed by framework hydrophobicity/hydrophilicity; in hydrophobic ZIF-8 and -95, water flux is higher than in hydrophilic ZIF-93 and -97. Furthermore, water molecules in ZIF 93 move slowly and remain in the membrane for a long time but undergo to-and-fro motion in ZIF-100. The lifetime of hydrogen bonds in ZIF-93 is found to be longer than in ZIF-100. This simulation study quantitatively elucidates the dynamic and structural properties of water in ZIF membranes, identifies the key governing factors (aperture size and framework hydrophobicity/hydrophilicity), and suggests that ZIF-100 is an intriguing membrane for seawater pervaporation. PMID- 27195442 TI - "Can a school-wide bullying prevention program improve the plight of victims? Evidence for risk * intervention effects": Correction to Juvonen et al. (2016). AB - Reports an error in "Can a school-wide bullying prevention program improve the plight of victims? Evidence for risk * intervention effects" by Jaana Juvonen, Hannah L. Schacter, Miia Sainio and Christina Salmivalli (Journal of Consulting and Clinical Psychology, 2016[Apr], Vol 84[4], 334-344). In the article there was an error in Table 2 of the Results. The Victimization, BL * Intervention interaction term was marked significant in the Attitudes Toward School column (".023(.02)**"). However, this interaction was not statistically significant and the two asterisks should be removed in Table 2. The correct table is provided. (The following abstract of the original article appeared in record 2016-03231 001.) OBJECTIVE: This study was designed to examine whether a school-wide antibullying program, effective in reducing incidents of bullying, can also reduce the harm associated with victimization. Specifically, we test whether baseline victimization moderates the KiVa program intervention effects on school perceptions, depression, and self-esteem. METHOD: Relying on a randomized control sample consisting of 7,010 fourth to sixth grade Finnish elementary school students, self-report data were examined using multilevel modeling across 39 intervention and 38 control schools over a 12-month period. RESULTS: The KiVa program was particularly effective in facilitating perceptions of a caring school climate among students who were most victimized before the intervention, while program benefits on attitudes toward school did not vary by level of victimization. The intervention effects on depression and self-esteem were strongest only among the most victimized sixth graders. CONCLUSIONS: The results suggest that antibullying programs designed to improve the school ecology can alleviate the plight of the victimized and underscore that harm reduction should be assessed by testing risk * intervention effects when evaluating effectiveness of such programs. (PsycINFO Database Record PMID- 27195443 TI - "A randomized controlled trial on the efficacy of mindfulness-based cognitive therapy and a group version of cognitive behavioral analysis system of psychotherapy for chronically depressed patients": Correction to Michalak et al. (2015). AB - Reports an error in "A randomized controlled trial on the efficacy of mindfulness based cognitive therapy and a group version of cognitive behavioral analysis system of psychotherapy for chronically depressed patients" by Johannes Michalak, Martin Schultze, Thomas Heidenreich and Elisabeth Schramm (Journal of Consulting and Clinical Psychology, 2015[Oct], Vol 83[5], 951-963). In the article there was an error in the Method section in the Statistical Analysis subsection. The last sentence in the seventh paragraph should read "A remitter was defined as a participant with a HAM-D score of 8 or less at posttreatment." (The following abstract of the original article appeared in record 2015-36864-001.) OBJECTIVE: Mindfulness-based cognitive therapy (MBCT) has recently been proposed as a treatment option for chronic depression. The cognitive behavioral analysis system of psychotherapy (CBASP) is the only approach specifically developed to date for the treatment of chronically depressed patients. The efficacy of MBCT plus treatment-as-usual (TAU), and CBASP (group version) plus TAU, was compared to TAU alone in a prospective, bicenter, randomized controlled trial. METHOD: One hundred and six patients with a current DSM-IV defined major depressive episode and persistent depressive symptoms for more than 2 years were randomized to TAU only (N = 35), or to TAU with additional 8-week group therapy of either 8 sessions of MBCT (n = 36) or CBASP (n = 35). The primary outcome measure was the Hamilton Depression Rating Scale (24-item HAM-D, Hamilton, 1967) at the end of treatment. Secondary outcome measures were the Beck Depression Inventory (BDI; Beck, Steer, & Brown, 1996) and measures of social functioning and quality of life. RESULTS: In the overall sample as well as at 1 treatment site, MBCT was no more effective than TAU in reducing depressive symptoms, although it was significantly superior to TAU at the other treatment site. CBASP was significantly more effective than TAU in reducing depressive symptoms in the overall sample and at both treatment sites. Both treatments had only small to medium effects on social functioning and quality of life. CONCLUSIONS: Further studies should inquire whether the superiority of CBASP in this trial might be explained by the more active, problem-solving, and interpersonal focus of CBASP. (PsycINFO Database Record PMID- 27195444 TI - An Expansile Petrous Apex Mass. PMID- 27195445 TI - Identification of glycoproteins associated with HIV latently infected cells using quantitative glycoproteomics. AB - HIV infection is not curable due to viral latency. Compelling reports suggest that there is a distinct profile of surface proteins that can be used for targeting latently infected cells. We have recently reported that glycoproteins were differentially secreted from HIV latently infected ACH-2 cells compared to the parental A3.01 cells. This finding suggests that glyco-phenotype might be different in these two cell lines. To determine the difference, the ACH-2 and A3.01 cell lines were subjected to a glycoproteomic analysis. A total number of 940 unique N-linked glycosite-containing peptides from 515 glycoproteins were identified. Among the glycoproteins, 365 and 104 were annotated as cell surface and membrane-associated proteins, respectively. Quantitative LC-MS/MS analysis revealed a change of 236 glycosite-containing peptides from 172 glycoproteins between the two cell lines without reactivation. Bioinformatic analysis suggests that cell adhesion, immune response, glycoprotein metabolic process, cell motion, and cell activation were associated with the changed proteins. After reactivation of latency, changes in glycosite-containing peptides were observed in both cell lines. The changed proteins suggest that cell migration, response to wounding and immune response might be impaired in reactivated latently infected cells. Glycoproteomics merits future application using primary cells to discover reveal mechanisms in HIV pathogenesis. PMID- 27195447 TI - Experiences of Informal Caregivers of Older Adults Transitioned From Nursing Homes to the Community Through the Money Follows the Person Demonstration. AB - This study examined experiences of 156 informal caregivers of older adults who transitioned to the community through the Connecticut Money Follows the Person (MFP) Rebalancing Demonstration after prolonged nursing home stays. Caregiver burden, positive aspects of caregiving, depressive symptoms, anxiety, and comparative subjective stress were examined in relation to caregiver demographics and care receiver characteristics with a cross-sectional survey. Caregivers reported low burden, depressive symptoms, and anxiety, and fairly high levels of positive aspects of caregiving and satisfaction with community services. Most caregivers were less stressed compared to the time the care recipient was in, or before they entered, a nursing home. Live-in caregivers experienced more positive aspects of caregiving, but adult children reported higher burden than other caregivers. Unmet service needs also increased caregiver burden. Programs like MFP are a viable option with broadly positive outcomes from a caregiver's perspective. Enthusiasm for increasing access to community care is growing for older adults who otherwise would reside in nursing homes for extended periods. Identifying unmet service needs and needs for targeted functional support could further enhance caregiver experiences and contribute to the successful transition of older adults to the community. PMID- 27195446 TI - Plasmon enhanced optical tweezers with gold-coated black silicon. AB - Plasmonic optical tweezers are a ubiquitous tool for the precise manipulation of nanoparticles and biomolecules at low photon flux, while femtosecond-laser optical tweezers can probe the nonlinear optical properties of the trapped species with applications in biological diagnostics. In order to adopt plasmonic optical tweezers in real-world applications, it is essential to develop large scale fabrication processes without compromising the trapping efficiency. Here, we develop a novel platform for continuous wave (CW) and femtosecond plasmonic optical tweezers, based on gold-coated black silicon. In contrast with traditional lithographic methods, the fabrication method relies on simple, single step, maskless tabletop laser processing of silicon in water that facilitates scalability. Gold-coated black silicon supports repeatable trapping efficiencies comparable to the highest ones reported to date. From a more fundamental aspect, a plasmon-mediated efficiency enhancement is a resonant effect, and therefore, dependent on the wavelength of the trapping beam. Surprisingly, a wavelength characterization of plasmon-enhanced trapping efficiencies has evaded the literature. Here, we exploit the repeatability of the recorded trapping efficiency, offered by the gold-coated black silicon platform, and perform a wavelength-dependent characterization of the trapping process, revealing the resonant character of the trapping efficiency maxima. Gold-coated black silicon is a promising platform for large-scale parallel trapping applications that will broaden the range of optical manipulation in nanoengineering, biology, and the study of collective biophotonic effects. PMID- 27195448 TI - Too little sleep and too much sleep among older adults: Associations with self reported sleep medication use, sleep quality and healthcare utilization. AB - AIM: The present study examined relationships among older adults' sleep duration (1-5 h and >=10 h vs 6-9 h), sleep medication use, sleep quality and healthcare use. METHODS: The 2013 USA National Health Interview Survey provided data on a sample of 7196 community-dwelling individuals aged >=65 years. Bivariate analyses and multivariate regression analyses were used to examine study questions. RESULTS: Of the sample, 85% slept 6-9 h on average, 8% slept 1-5 h and 7% slept >=10 h. One-sixth of optimal sleepers, one-quarter of short sleepers and one fifth of long sleepers used sleep medications at least once in the preceding week. Medication intake of one to two times, as opposed to non-use, was associated with a greater risk of short than optimal sleep (RRR 1.60, 95% CI 1.03 2.48). Short sleep was positively, but long sleep was negatively associated with trouble falling asleep and staying asleep. Any medication use was positively associated with trouble falling asleep and staying asleep. Short sleep was associated with greater odds of emergency department visits (OR 1.36, 95% CI 1.06 1.77), whereas long sleep was associated with greater odds of an overnight hospital stay (OR 1.48, 95% CI 1.04-2.11) and home care use (OR 2.46, 95% CI 1.37 4.41). Medication intake one to two times was associated with greater odds of emergency department visits (OR 1.48, 95% CI 1.11-1.98). CONCLUSIONS: Sleep medication use does not appear to promote sleep health. Both short and long sleep durations are associated with a higher likelihood of healthcare use. Clinicians need to examine older adults' sleep health and medication use, and their effects on healthcare use. Geriatr Gerontol Int 2017; 17: 545-553. PMID- 27195449 TI - Has the introduction of antibiotic-impregnated external ventricular drain catheters changed the nature of the microorganisms cultured in patients with drain-related infection? A single neurosurgical centre's experience. AB - BACKGROUND: The introduction of antibiotic-impregnated catheters (AICs) has significantly reduced external ventricular drain (EVD) infection rates, inhibiting in particular Gram-positive microbial infection. There is a theoretical increased risk of selection of resistant and Gram-negative microorganisms. The aim of this study is to look at the impact of the introduction of AICs on microorganism susceptibility of infected EVDs and to determine whether the use of such devices results in shift from Gram-positive to Gram-negative microorganisms. A secondary aim is to determine if a change in routine empiric antimicrobial therapy is required because of a change in the microorganism(s) causing infection. METHODS: Retrospective analysis of EVDs inserted as a primary procedure or part of a concomitant neurosurgical procedure in 2006 (pre-AIC) and 2012 (post-AIC Codman Bactiseal((c)) impregnated with clindamycin 0.15% and rifampicin 0.054%). EVD-related infection was defined as a cerebral spinal fluid sample with a positive culture with some patients having one or more microorganisms infecting the same EVD at the same time. Sixty-five EVDs over 843 days and 66 EVDs over 619 days were inserted respectively in each cohort. RESULTS: In 2006, 9 of 35 patients developed EVD-related infection and 13 microorganisms were cultured; 8 of which were Gram-positive and 4 Gram-negative. Four of 49 patients developed EVD-related infection in 2012 and six microorganisms were cultured; four Gram-positive and two Gram-negative. The cumulative incidence of EVDs becoming infected is 18.5% (12/65) and 6.1% (4/66; p = 0.03) in 2012. The EVD-associated infection rate was 14.2 per 1000 EVD days and 6.5 per 1000 EVD days in 2012. There was no change in mortality. CONCLUSIONS: The study demonstrates that within a single neurosurgical centre there have been neither changes in susceptibility of microorganisms nor a change from predominately Gram-positive to Gram-negative microorganisms infecting EVDs following the switch to AIC. The infection rate has significantly reduced due to change in catheter type. PMID- 27195450 TI - Patient perceptions of a 1-h art-making experience during blood and marrow transplant treatment. AB - Patients with various forms of cancer receiving blood and marrow transplant (BMT) treatment at an outpatient clinic develop chemotherapy-related symptoms and an increased desire to use complementary and alternative medicine in order to address these symptoms. Art-making offers an inexpensive way to pass time and relieve symptoms during long hours in treatment. Twenty-one BMT patients painted a tile and participated in research. Researchers used semi-structured interviews to understand patients' experiences with art-making. Interviews were recorded, transcribed and coded independently by researchers who met to agree on themes. Ten themes emerged from the data including, meaningful activity (32.2%), expression (18.7%), passing time (13.2%), BMT process (12.1%), social outlet (8.1%), therapy-related symptoms (7.3%), negative aspects of painting (5.9%) and encouragement to paint (2.6%). The results of this study revealed that art-making experience can provide patients a meaningful activity during treatment and an outlet to express their feelings. PMID- 27195451 TI - Worse cardiac remodeling in response to pressure overload in type 2 diabetes mellitus. AB - BACKGROUND: Diabetic cardiomyopathy is characterized by cardiac structural and functional abnormalities. Additionally, chronic pressure overload conditions are highly prevalent amongst diabetic population and this association leads to a more severe myocardial impairment. The differences in myocardial pathophysiology between type 1 and type 2 diabetes mellitus (DM) still remain to be clarified. Thus, we aimed to investigate biventricular structural and functional changes promoted by the two types of DM and the impact of concomitant chronic pressure overload. METHODS: Wistar rats were injected with streptozotocin (Type 1 DM, T1DM) or fed with a hypercaloric diet (Type 2 DM, T2DM). Pressure overload was imposed in DM animals by aortic constriction and after 5weeks of DM the cardiac function and structure were evaluated. RESULTS: Both types of DM promoted hypertrophy, increased fibrosis and advanced glycation end-products deposition, in the two ventricles. Interestingly, the induced myocardial alterations were distinct. While T1DM stimulated a pronounced hypertrophy and extracellular matrix remodeling, T2DM induced functional impairment. The negative impact of the association of DM with aortic constriction was more pronounced in T2DM, promoting impaired function and increased stiffness, particularly in the right ventricle. CONCLUSIONS: Our study demonstrated that the two types of diabetes induce distinct cardiac alterations per se or when combined with chronic pressure overload. T1DM promoted a more extensive remodeling in cardiac structure while T2DM significantly impaired ventricular function. The impact of pressure overload was more notorious in T2DM as observed by worse myocardial remodeling, suggesting a higher susceptibility to the deleterious effects of chronic pressure overload, namely hypertension, among this diabetic population. PMID- 27195452 TI - Legal and Ethical Implications of Data Sharing in International Biobanking Research: Toward a Global Response. PMID- 27195453 TI - Long-term climate impacts on breeding bird phenology in Pennsylvania, USA. AB - Climate change is influencing bird phenology worldwide, but we still lack information on how many species are responding over long temporal periods. We assessed how climate affected passerine reproductive timing and productivity at a constant effort mist-netting station in western Pennsylvania using a model comparison approach. Several lines of evidence point to the sensitivity of 21 breeding passerines to climate change over five decades. The trends for temperature and precipitation over 53 years were slightly positive due to intraseasonal variation, with the greatest temperature increases and precipitation declines in early spring. Regardless of broodedness, migration distance, or breeding season, 13 species hatched young earlier over time with most advancing >3 days per decade. Warm springs were associated with earlier captures of juveniles for 14 species, ranging from 1- to 3-day advancement for every 1 degrees C increase. This timing was less likely to be influenced by spring precipitation; nevertheless, higher rainfall was usually associated with later appearance of juveniles and breeding condition in females. Temperature and precipitation were positively related to productivity for seven and eleven species, respectively, with negative relations evident for six and eight species. We found that birds fledged young earlier with increasing spring temperatures, potentially benefiting some multibrooded species. Indeed, some extended the duration of breeding in these warm years. Yet, a few species fledged fewer juveniles in warmer and wetter seasons, indicating that expected future increases could be detrimental to locally breeding populations. Although there were no clear relationships between life history traits and breeding phenology, species specific responses to climate found in our study provide novel insights into phenological flexibility in songbirds. Our research underscores the value of long term monitoring studies and the importance of continuing constant effort sampling in the face of climate change. PMID- 27195454 TI - Late Toxicities of Intensity-Modulated Radiation Therapy for Head and Neck Rhabdomyosarcoma. AB - PURPOSE/OBJECTIVES: To examine the late effects of intensity-modulated radiation therapy (IMRT) in pediatric patients with rhabdomyosarcoma of the head and neck. MATERIALS/METHODS: All 1-year survivors of pediatric head and neck rhabdomyosarcoma treated with IMRT at a single institution from 1999 to 2014 were assessed for long-term complications. Late toxicities were graded according to CTCAE version 4.03. RESULTS: Among 30 patients, median age at IMRT was 7.4 (1.5 20.8) years, median follow-up was 7.7 (1.2-14.4) years, and median IMRT dose was 50.4 (36-50.4) Gy. Tumor subsites included parameningeal (80%), orbit (13%), and other (7%). Common late toxicities were facial disfigurement (n = 23, 77%), growth hormone deficiency (n = 11, 37%), cataract (n = 10, 34%), and dental problems (n = 10, 33%). Twenty-two patients (73%) had >=2 late toxicities and 14 patients (47%) had >=3 late toxicities. Seventeen patients (57%) experienced grade 2 toxicity and 10 patients (33%) had grade 3 toxicity. Grade 3 toxicities included visual disturbance, cataract, facial disfigurement, chronic sinusitis/otitis, and hearing loss. Severe facial deformity was noted in nine patients (30%), and three patients underwent cosmetic surgery. Patients with severe facial deformity were treated at younger ages (median 6.0 years vs. 8.1 years for patients with no/nonsevere facial deformity) and more likely to have infratemporal fossa tumors. There were no secondary solid malignancies. CONCLUSIONS: Late radiation toxicities are common in survivors of pediatric head and neck rhabdomyosarcoma treated with IMRT. While the majority of late effects are mild-moderate, they can significantly impact quality of life, particularly facial disfigurement. PMID- 27195456 TI - Physical and psychological benefits of once-a-week Pilates exercises in young sedentary women: A 10-week longitudinal study. AB - Pilates exercises have several demonstrated physical and psychological benefits. To date, most research in this context was conducted with symptomatic or elderly people with few dependent measures. The current study examined the chronic or longitudinal effects of very low frequency, once a week, Pilates training on several physical and psychological measures, over a 10-week intervention, in young, healthy, and sedentary women. Further, the study gauged the acute effects of Pilates exercises on positive- and negative affect in 10 exercise sessions. Compared to a control group, the Pilates group exhibited significant improvements in skeletal muscle mass, flexibility, balance, core- and abdominal muscle strength, body awareness, and negative affect. This group also showed favorable changes in positive (22.5% increase) and negative affect (12.2% decrease) in nine out of ten exercise sessions. This work clearly demonstrates the acute and chronic benefits of Pilates training on both physical and psychological measures. It also reveals that even only once a week Pilates training is enough to trigger detectable benefits in young sedentary women. While this frequency is below the required levels of exercise for health, it may overcome the 'lack of time' excuse for not exercising and subsequently its tangible benefits may positively influence one's engagement in more physical activity. PMID- 27195457 TI - Gender differences in the association between objective sleep quality and leukocyte count: The HEIJO-KYO cohort. AB - Chronic low-grade systemic inflammation increases cardiovascular risk and mortality. Subjective assessment of sleep quality in previous observational studies has demonstrated associations with biomarkers of systemic inflammation, although the results are conflicting. In this cross-sectional study on 1098 elderly individuals, circulating white blood cell (WBC) count and actigraphic sleep quality were measured as indices of systemic inflammation and objective sleep quality, respectively. Lower sleep efficiency (SE) and longer wake after sleep onset (WASO) were significantly associated with increased WBC count in females (n=581) but no significant associations were observed in the association between WBC count and all objective sleep parameters in males (n=517). The associations of lower SE and longer WASO with increased WBC count in females remained significant in multivariable models adjusted for potential confounding factors. These results indicated that a 1-standard deviation increase in SE (8.0%) and WASO (27.7min) corresponded to a 0.16*10(9)/L (95% confidence interval: 0.05 to 0.27*10(9)/L) decrease and 0.14*10(9)/L (95% confidence interval: 0.03 to 0.25*10(9)/L) increase in circulating WBC count, respectively. In contrast, total sleep time and sleep onset latency were not significantly associated with WBC count in multivariable models. In conclusion, decrease in objectively measured sleep quality was significantly associated with increased circulating WBC count in females but not males, independently of known factors related to systemic inflammation including age, obesity, smoking, hypertension, diabetes, and physical inactivity. PMID- 27195455 TI - MCH receptor deletion does not impair glucose-conditioned flavor preferences in mice. AB - The post-oral actions of glucose stimulate intake and condition flavor preferences in rodents. Hypothalamic melanin-concentrating hormone (MCH) neurons are implicated in sugar reward, and this study investigated their involvement in glucose preference conditioning in mice. In Exp. 1 MCH receptor 1 knockout (KO) and C57BL/6 wildtype (WT) mice learned to prefer 8% glucose over an initially more-preferred non-nutritive 0.1% sucralose+saccharin (S+S) solution. In contrast, the KO and WT mice preferred S+S to 8% fructose, which is consistent with this sugar's weak post-oral reinforcing action. In Exp. 2 KO and WT mice were trained to drink a flavored solution (CS+) paired with intragastric (IG) infusion of 16% glucose and a different flavored solution (CS-) paired with IG water. Both groups drank more CS+ than CS- in training and preferred the CS+ to CS- in a 2-bottle test. These results indicate that MCH receptor signaling is not required for flavor preferences conditioned by the post-oral actions of glucose. This contrasts with other findings implicating MCH signaling in other types of sugar reward processing. PMID- 27195459 TI - Physiological and behavioral responses in Drosophila melanogaster to odorants present at different plant maturation stages. AB - The fruit fly Drosophila melanogaster feeds and oviposits on fermented fruit, hence its physiological and behavioral responses are expected to be tuned to odorants abundant during later stages of fruit maturation. We used a population of about two-hundred isogenic lines of D. melanogaster to assay physiological responses (electroantennograms (EAG)) and behavioral correlates (preferences and choice ratio) to odorants found at different stages of fruit maturation. We quantified electrophysiological and behavioral responses of D. melanogaster for the leaf compound beta-cyclocitral, as well as responses to odorants mainly associated with later fruit maturation stages. Electrophysiological and behavioral responses were modulated by the odorant dose. For the leaf compound we observed a steep dose-response curve in both EAG and behavioral data and shallower curves for odorants associated with later stages of maturation. Our data show the connection between sensory and behavioral responses and are consistent with the specialization of D. melanogaster on fermented fruit and avoidance of high doses of compounds associated with earlier stages of maturation. Odor preferences were modulated in a non-additive way when flies were presented with two alternative odorants, and combinations of odorants elicited higher responses than single compounds. PMID- 27195460 TI - Sex differences and estrous cycle effects on foreground contextual fear conditioning. PMID- 27195461 TI - Hypobaric Treatment Effects on Chilling Injury, Mitochondrial Dysfunction, and the Ascorbate-Glutathione (AsA-GSH) Cycle in Postharvest Peach Fruit. AB - In this study, hypobaric treatment effects were investigated on chilling injury, mitochondrial dysfunction, and the ascorbate-glutathione (AsA-GSH) cycle in peach fruit stored at 0 degrees C. Internal browning of peaches was dramatically reduced by applying 10-20 kPa pressure. Hypobaric treatment markedly inhibited membrane fluidity increase, whereas it kept mitochondrial permeability transition pore (MPTP) concentration and cytochrome C oxidase (CCO) and succinic dehydrogenase (SDH) activity relatively high in mitochondria. Similarly, 10-20 kPa pressure treatment reduced the level of decrease observed in AsA and GSH concentrations, while it enhanced ascorbate peroxidase (APX), glutathione reductase (GR), and monodehydroascorbate reductase (MDHAR) activities related to the AsA-GSH cycle. Furthermore, comparative transcriptomic analysis showed that differentially expressed genes (DEGs) associated with the metabolism of glutathione, ascorbate, and aldarate were up-regulated in peaches treated with 10 20 kPa for 30 days at 0 degrees C. Genes encoding GR, MDHAR, and APX were identified and exhibited higher expression in fruits treated with low pressure than in fruits treated with normal atmospheric pressure. Our findings indicate that the alleviation of chilling injury by hypobaric treatment was associated with preventing mitochondrial dysfunction and triggering the AsA-GSH cycle by the transcriptional up-regulation of related enzymes. PMID- 27195462 TI - SPRINT Results in Older Patients: How Low to Go? PMID- 27195458 TI - Hypothalamic-pituitary-adrenocortical axis dysfunction in epilepsy. AB - Epilepsy is a common neurological disease, affecting 2.4million people in the US. Among the many different forms of the disease, temporal lobe epilepsy (TLE) is one of the most frequent in adults. Recent studies indicate the presence of a hyperactive hypothalamopituitary- adrenocortical (HPA) axis and elevated levels of glucocorticoids in TLE patients. Moreover, in these patients, stress is a commonly reported trigger of seizures, and stress-related psychopathologies, including depression and anxiety, are highly prevalent. Elevated glucocorticoids have been implicated in the development of stress-related psychopathologies. Similarly, excess glucocorticoids have been found to increase neuronal excitability, epileptiform activity and seizure susceptibility. Thus, patients with TLE may generate abnormal stress responses that both facilitate ictal discharges and increase vulnerability for the development of comorbid psychopathologies. Here, we will examine the evidence that the HPA axis is disrupted in TLE, consider potential mechanisms by which this might occur, and discuss the implications of HPA dysfunction for seizuretriggering and psychiatric comorbidities. PMID- 27195464 TI - Physiological and Biochemical Responses to Continuous Saline Irrigation Inside the Abdominal Cavity in Anesthetized Pigs. AB - BACKGROUND: Water-filled laparoendoscopic surgery (WaFLES) has been proposed as a novel surgical system achieving a wide surgical field in the intra- and extraperitoneal space with continuous irrigation of isotonic fluid into the field. Despite its technical feasibility and advantages, the safety of the technique, particularly with respect to physiological functions, has not been evaluated. METHODS: Various types of minor abdominal surgeries were performed under general anesthesia in nine adult pigs either by conventional laparoscopy (n = 3) or WaFLES (n = 6). In addition to esophageal temperature and body weight, cardiorespiratory variables such as blood pressure, heart rate, and arterial blood gas parameters were compared before and after the surgeries. Blood samples were obtained for assessing changes in biochemical parameters before and after the surgeries. RESULTS: Three to seven hours of various surgeries were completed without critical cardiorespiratory events in all animals. Oxygenation and ventilation were maintained regardless of the techniques used for the surgeries. A minor increase of body weight (2.5% of initial body weight), metabolic acidosis, hyperkalemia, and impaired hepatic function were observed after WaFLES surgeries. CONCLUSIONS: The preliminary study indicated no serious immediate adverse effects of the WaFLES technique. PMID- 27195463 TI - Antiviral Activity of Oroxylin A against Coxsackievirus B3 Alleviates Virus Induced Acute Pancreatic Damage in Mice. AB - The flavonoids mosloflavone, oroxylin A, and norwogonin, which were purified from Scutellaria baicalensis Georgi, significantly protected Vero cells against Coxsackievirus B3 (CVB3)-induced cell death. To investigate the in vivo antiviral activity of oroxylin A, we intraperitoneally inoculated CVB3 into 4-week-old BALB/c mice. Body weights and blood glucose levels of the mice were decreased after CVB3 infection, and these changes were attenuated by the administration of oroxylin A. Importantly, treatment of mice with oroxylin A reduced viral titers in the pancreas and decreased the serum levels of the inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor (TNF)-alpha. Additionally, the administration of oroxylin A mitigated the histological pancreatic lesions and apoptotic cell death induced by CVB3 infection and increased the levels of phospho-eIF2alpha in infected pancreata. The results suggest that oroxylin A may represent a potent antiviral agent against CVB3 infection. PMID- 27195466 TI - Leadership in Neonatal Nursing. PMID- 27195468 TI - A New Web Site, Upcoming Conference, and Collaboration to Boost Therapies for Newborns. PMID- 27195465 TI - Quantification of Trunk Postural Stability Using Convex Polyhedron of the Time Series Accelerometer Data. AB - Techniques to quantify postural stability usually rely on the evaluation of only two variables, that is, two coordinates of COP. However, by using three variables, that is, three components of acceleration vector, it is possible to describe human movement more precisely. For this purpose, a single three-axis accelerometer was used, making it possible to evaluate 3D movement by use of a novel method, convex polyhedron (CP), together with a traditional method, based on area of the confidence ellipse (ACE). Ten patients (Pts) with cerebellar ataxia and eleven healthy individuals of control group (CG) participated in the study. The results show a significant increase of volume of the CP (CPV) in Pts or CG standing on foam surface with eyes open (EO) and eyes closed (EC) after the EC phase. Significant difference between Pts and CG was found in all cases as well. Correlation coefficient indicates strong correlation between the CPV and ACE in most cases of patient examinations, thus confirming the possibility of quantification of postural instability by the introduced method of CPV. PMID- 27195469 TI - Standard for Maintaining the Competence of Neonatal Nurse Practitioners: Executive Summary Position Statement 3050: From the National Association of Neonatal Nurses. PMID- 27195470 TI - Applying Adult Ventilator-associated Pneumonia Bundle Evidence to the Ventilated Neonate. AB - BACKGROUND: Ventilator-associated pneumonia (VAP) in neonates can be reduced by implementing preventive care practices. Implementation of a group, or bundle, of evidence-based practices that improve processes of care has been shown to be cost effective and to have better outcomes than implementation of individual single practices. PURPOSE: The purpose of this article is to describe a safe, effective, and efficient neonatal VAP prevention protocol developed for caregivers in the neonatal intensive care unit (NICU). Improved understanding of VAP causes, effects of care practices, and rationale for interventions can help reduce VAP risk to neonatal patients. METHOD: In order to improve care practices to affect VAP rates, initial and annual education occurred on improved protocol components after surveying staff practices and auditing documentation compliance. FINDINGS/RESULTS: In 2009, a tertiary care level III NICU in the Midwestern United States had 14 VAP cases. Lacking evidence-based VAP prevention practices for neonates, effective adult strategies were modified to meet the complex needs of the ventilated neonate. A protocol was developed over time and resulted in an annual decrease in VAP until rates were zero for 20 consecutive months from October 2012 to May 2014. IMPLICATIONS FOR PRACTICE: This article describes a VAP prevention protocol developed to address care practices surrounding hand hygiene, intubation, feeding, suctioning, positioning, oral care, and respiratory equipment in the NICU. IMPLICATIONS FOR RESEARCH: Implementation of this VAP prevention protocol in other facilities with appropriate monitoring and tracking would provide broader support for standardization of care. Individual components of this VAP protocol could be studied to strengthen the inclusion of each; however, bundled interventions are often considered stronger when implemented as a whole. PMID- 27195471 TI - What Is Best Practice for Providing Pain Relief During Retinopathy of Prematurity Eye Examinations? AB - BACKGROUND: Retinopathy of prematurity screenings is considered a painful procedure. Yet, preterm infants 30 weeks of gestation or less or weighing 1500 g or less or between 1500 and 2000 g or greater than 30 weeks of gestation with an unstable course are required to have these examinations until their eyes reach maturity. PURPOSE: A systematic search of the literature was conducted to answer the question "For premature infants undergoing retinal eye examinations, what interventions are the most effective for pain reduction?" METHODS/SEARCH STRATEGY: CINAHL Plus and MEDLINE were searched using the key words: retinopathy of prematurity and pain. The search was limited to the last 10 years and experimental or quasi-experimental studies attempting to reduce pain during eye examinations. FINDINGS/RESULTS: The search criteria yielded 14 studies that addressed interventions to decrease pain during examinations. Three strategies were noted for pain relief including nonpharmacological interventions (n = 9), topical anesthetics (n = 3), and examination techniques (n = 2). The findings indicate that these 3 strategies provided varying results for pain relief but could be beneficial if provided in a consistent protocol. IMPLICATIONS FOR PRACTICE: Consequently, policies for pain management during retinopathy of prematurity examinations need to be used consistently. It is important for clinicians to consider using a combination of strategies that maximize comfort and provide pain relief. IMPLICATIONS FOR RESEARCH: There remains a need to continue to examine pain-relieving techniques for retinopathy of prematurity examinations. Further investigation is needed to evaluate effective strategies that mitigate pain and the pathways causing pain. In addition, investigating the clinical feasibility of examinations without speculum use may be worthwhile. PMID- 27195472 TI - CLABSI Reduction Strategy: A Systematic Central Line Quality Improvement Initiative Integrating Line-Rounding Principles and a Team Approach. PMID- 27195474 TI - Multiparametric human hepatocellular carcinoma characterization and therapy response evaluation by hyperpolarized (13) C MRSI. AB - Individual tumor characterization and treatment response monitoring based on current medical imaging methods remain challenging. This work investigates hyperpolarized (13) C compounds in an orthotopic rat hepatocellular carcinoma (HCC) model system before and after transcatheter arterial embolization (TAE). HCC ranks amongst the top six most common cancer types in humans and accounts for one-third of cancer-related deaths worldwide. Early therapy response monitoring could aid in the development of personalized therapy approaches and novel therapeutic concepts. Measurements with selectively (13) C-labeled and hyperpolarized urea, pyruvate and fumarate were performed in tumor-bearing rats before and after TAE. Two-dimensional, slice-selective MRSI was used to obtain spatially resolved maps of tumor perfusion, cell energy metabolic conversion rates and necrosis, which were additionally correlated with immunohistochemistry. All three injected compounds, taken together with their respective metabolites, exhibited similar signal distributions. TAE induced a decrease in blood flow into the tumor and thus a decrease in tumor to muscle and tumor to liver ratios of urea, pyruvate and its metabolites, alanine and lactate, whereas conversion rates remained stable or increased on TAE in tumor, muscle and liver tissue. Conversion from fumarate to malate successfully indicated individual levels of necrosis, and global malate signals after TAE suggested the washout of fumarase or malate itself on necrosis. This study presents a combination of three (13) C compounds as novel candidate biomarkers for a comprehensive characterization of genetically and molecularly diverse HCC using hyperpolarized MRSI, enabling the simultaneous detection of differences in tumor perfusion, metabolism and necrosis. If, as in this study, bolus dynamics are not required and qualitative perfusion information is sufficient, the desired information could be extracted from hyperpolarized fumarate and pyruvate alone, acquired at higher fields with better spectral separation. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27195475 TI - Reelin-immunoreactive neurons in entorhinal cortex layer II selectively express intracellular amyloid in early Alzheimer's disease. AB - The onset of Alzheimer's disease (AD) is associated with subtle pathological changes including increased intracellular expression of amyloid-beta (Abeta). A structure affected particularly early in the course of AD is the entorhinal cortex, where neuronal death in layer II is observed already at initial stages. Neurons in EC-layer II, particularly those that express the protein Reelin, give rise to projections to the hippocampal dentate gyrus and this projection shows severe loss of synaptic contacts during early-stage AD. Given this anatomical specificity, we sought to determine whether increased intracellular expression of Abeta is selectively associated with Reelin-immunoreactive neurons in layer II of the entorhinal cortex. Here we report that in a transgenic rat model, which mimics the onset and distribution of extracellular amyloid deposits seen in human AD subjects, expression of intracellular Abeta in entorhinal layer II selectively occurs in Reelin-immunoreactive neurons during the early, pre-plaque stage. This Reelin-Abeta association is also present in human subjects with AD-related pathological changes, even in early disease stages. These findings strongly indicate that Reelin-immunoreactive neurons in entorhinal layer II play a crucial role during the initial stages of AD, and may therefore lead to refined hypotheses concerning the origin of this devastating condition. PMID- 27195473 TI - Heatwaves and Hospital Admissions for Mental Disorders in Northern Vietnam. AB - Studies in high-income countries have shown an association between heatwaves and hospital admissions for mental disorders. It is unknown whether such associations exist in subtropical nations like Vietnam. The study aim was to investigate whether hospital admissions for mental disorders may be triggered, or exacerbated, by heat exposure and heatwaves, in a low- and middle-income country, Vietnam. For this, we used data from the Hanoi Mental Hospital over five years (2008-2012) to estimate the effect of heatwaves on admissions for mental disorders. A zero-inflated negative binomial regression model accounting for seasonality, time trend, days of week, and mean humidity was used to analyse the relationship. Heatwave events were mainly studied as periods of three or seven consecutive days above the threshold of 35 degrees C daily maximum temperature (90th percentile). The study result showed heatwaves increased the risk for admission in the whole group of mental disorders (F00-79) for more persistent heatwaves of at least 3 days when compared with non-heatwave periods. The relative risks were estimated at 1.04 (0.95-1.13), 1.15 (1.005-1.31), and 1.36 (1 1.90) for a one-, three- and seven-day heatwave, respectively. Admissions for mental disorders increased among men, residents in rural communities, and the elderly population during heatwaves. The groups of organic mental disorders, including symptomatic illnesses (F0-9) and mental retardation (F70-79), had increased admissions during heatwaves. The findings are novel in their focus on heatwave impact on mental diseases in a population habituating in a subtropical low- and middle-income country characterized by rapid epidemiological transitions and environmental changes. PMID- 27195476 TI - Characterization of Three Tailoring Enzymes in Dutomycin Biosynthesis and Generation of a Potent Antibacterial Analogue. AB - The anthracycline natural product dutomycin and its precursor POK-MD1 were isolated from Streptomyces minoensis NRRL B-5482. The dutomycin biosynthetic gene cluster was identified by genome sequencing and disruption of the ketosynthase gene. Two polyketide synthase (PKS) systems are present in the gene cluster, including a type II PKS and a rare highly reducing iterative type I PKS. The type I PKS DutG repeatedly uses its active sites to create a nine-carbon triketide chain that is subsequently transferred to the alpha-l-axenose moiety of POK-MD1 at 4"-OH to yield dutomycin. Using a heterologous recombination approach, we disrupted a putative methyltransferase gene (dutMT1) and two glycosyltransferase genes (dutGT1 and dutGT2). Analysis of the metabolites of these mutants revealed the functions of these genes and yielded three dutomycin analogues SW140, SW91, and SW75. The major product SW91 in Streptomyces minoensis NRRL B-5482 DeltaDutMT1 was identified as 12-desmethyl-dutomycin, suggesting that DutMT1 is the dedicated 12-methyltransferase. This was confirmed by the in vitro enzymatic assay. DutGT1 and DutGT2 were found to be responsible for the introduction of beta-d-amicetose and alpha-l-axenose, respectively. Dutomycin and SW91 showed strong antibacterial activity against Staphylococcus aureus and methicillin resistant S. aureus, whereas POK-MD1 and SW75 had no obvious inhibition, which revealed the essential role of the C-4" triketide chain in antibacterial activity. The minimal inhibitory concentration of SW91 against the two strains was 0.125 MUg mL(-1), lower than that of dutomycin (0.25 MUg mL(-1)), indicating that the antibacterial activity of dutomycin can be improved through biosynthetic structural modification. PMID- 27195477 TI - X-ray and Neutron Scattering of Water. AB - This review article focuses on the most recent advances in X-ray and neutron scattering studies of water structure, from ambient temperature to the deeply supercooled and amorphous states, and of water diffusive and collective dynamics, in disparate thermodynamic conditions and environments. In particular, the ability to measure X-ray and neutron diffraction of water with unprecedented high accuracy in an extended range of momentum transfers has allowed the derivation of detailed O-O pair correlation functions. A panorama of the diffusive dynamics of water in a wide range of temperatures (from 400 K down to supercooled water) and pressures (from ambient up to multiple gigapascals) is presented. The recent results obtained by quasi-elastic neutron scattering under high pressure are compared with the existing data from nuclear magnetic resonance, dielectric and infrared measurements, and modeling. A detailed description of the vibrational dynamics of water as measured by inelastic neutron scattering is presented. The dependence of the water vibrational density of states on temperature and pressure, and in the presence of biological molecules, is discussed. Results about the collective dynamics of water and its dispersion curves as measured by coherent inelastic neutron scattering and inelastic X-ray scattering in different thermodynamic conditions are reported. PMID- 27195479 TI - Quantification of Spontaneous W/O Emulsification and its Impact on the Swelling Kinetics of Multiple W/O/W Emulsions. AB - An osmotic imbalance between the two water phases of multiple water-in-oil-in water (W1/O/W2) emulsions results in either emulsion swelling or shrinking due to water migration across the oil layer. Controlled mass transport is not only of importance for emulsion stability but also allows transient emulsion thickening or the controlled release of encapsulated substances, such as nutriments or simply salt. Our prior work has shown that mass transport follows two sequential stages. In the first stage, the oil-phase structure is changed in a way that allows rapid, osmotically driven water transport in the second, osmotically dominated stage. These structural changes in the oil layer are strongly facilitated by the spontaneous formation of tiny water droplets in the oil phase, induced by the oil-soluble surfactant, i.e., polyglycerol polyricinoleate (PGPR). This study provides a simple method based on microscopy image analysis, allowing a detailed investigation of spontaneous W/O emulsification. It quantitatively describes the volume of droplets generated and the rate of droplet creation. Moreover, it describes the effect of spontaneous W/O emulsification on the swelling kinetics of microfluidic processed W1/O/W2 emulsions. Two different concentration regimes of the oil-soluble surfactant are identified: below a critical concentration the overall water transport rate increases, and above a critical concentration water transport stagnates because of maximized structure formation. PMID- 27195478 TI - Good job, bad job: Occupational perceptions among Latino poultry workers. AB - OBJECTIVES: Immigrant workers frequently take jobs that are physically demanding, provide low wages, and result in injuries (e.g., poultry production and processing). Through a qualitative approach, this paper elicits poultry workers' evaluations of their jobs and set them in the larger context of their lives. METHODS: Semi-structured interviews were conducted with 65 poultry workers in western North Carolina. Workers were asked to discuss job characteristics, physical and psychological impacts of their employment, and perceived health risks. RESULTS: Immigrant workers valued the stability, benefits, upward mobility, and pay offered. They disliked the physical demands, the potential perceived effects of the job on their health, and the interactions with bosses and peers. CONCLUSIONS: Workers' willingness to endure dirty, dangerous, and demanding (3-D) conditions of poultry must be understood in the context of other employment options, structural violence, and their focus on immediate family needs that positive aspects of these jobs can fulfill. Am. J. Ind. Med. 59:877 886, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27195480 TI - Phase Transition and Dynamics in Imidazolium-Based Ionic Liquid Crystals through a Metastable Highly Ordered Smectic Phase. AB - The phase transition behavior and dynamics of ionic liquid crystals, 1-methyl-3 alkylimidazolium tetrafluoroborate with various alkyl chain lengths, were investigated by X-ray scattering, differential scanning calorimetry, optical microscopy, and dielectric relaxation spectroscopy to elucidate the mechanism of their structural and phase changes. A metastable phase was found to appear via a supercooled smectic phase on cooling. In the metastable phase, disorder in the smectic phase is partially frozen; thus, the phase has order higher than that of the smectic phase but lower than that of the crystalline phase. During the subsequent heating process, the frozen disorder activates, and a crystalline phase appears in the supercooled smectic phase before entering the smectic phase. The relationship between the phase behavior and the dynamics of charge carriers such as ions is also discussed. PMID- 27195481 TI - Race/ethnicity-specific disparities in cancer incidence, burden of disease, and overall survival among patients with hepatocellular carcinoma in the United States. AB - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the fastest rising causes of cancer-related deaths in the United States, with disparities observed in cancer incidence and survival between ethnic groups. This report provides updated analyses on race-specific disparities in US HCC trends. METHODS: This large, population-based cohort study was conducted using Surveillance, Epidemiology, and End Results cancer registry data from 2003 to 2011 to investigate race-specific disparities in HCC incidence and survival. Survival was analyzed using Kaplan Meier methods and multivariate Cox proportional-hazards models. RESULTS: From 2003 to 2011, Asians had the highest HCC incidence, followed by blacks, Hispanics, and non-Hispanic whites. During the same period, Hispanics had the greatest increase in HCC incidence (+35.8%), whereas Asians experienced a 5.5% decrease. Although patients aged >=65 years had the highest HCC incidence among all racial/ethnic groups, the higher HCC incidence in Asians was observed only for patients ages <50 and >=65 years, whereas HCC incidence among patients ages 50 to 64 years was similar among Asians, blacks, and Hispanics. The overall 5 year HCC survival rate was highest among Asians (26.1%; 95% confidence interval [CI], 24.5%-27.6%) and lowest among blacks (21.3%; 95% CI, 19.5%-23.1%). On multivariate regression, Asians (hazard ratio, 0.83; 95% CI, 0.79-0.87; P < .001) and blacks (hazard ratio, 0.94; 95% CI, 0.89-0.99; P = .01) had significantly higher survival compared with non-Hispanic whites. CONCLUSIONS: Asians were the only group to demonstrate a declining HCC incidence in the form of a shift from advanced HCC to more localized HCC. These findings most likely reflect improved screening and surveillance efforts for this group. Cancer 2016;122:2512-23. (c) 2016 American Cancer Society. PMID- 27195483 TI - Band structure of a three-dimensional topological insulator quantum wire in the presence of a magnetic field. AB - By means of a numerical diagonalization approach, we calculate the electronic structure of a three-dimensional topological insulator (3DTI) quantum wire (QW) in the presence of a magnetic field. The QW can be viewed as a 3DTI film with lateral surfaces, when its rectangular cross section has a large aspect ratio. Our calculation indicates that nonchiral edge states emerge because of the confined states at the lateral surfaces. These states completely cover the valence band region among the Landau levels, which reasonably account for the absence of the [Formula: see text] quantum Hall effect in the relevant experimental works. In an ultrathin 3DTI film, inversion between the electron type and hole-type bands occurs, which leads to the so-called pseudo-spin Hall effect. In a 3DTI QW with a square cross section, a tilting magnetic field can establish well-defined Landau levels in all four surfaces. In such a case, the quantum Hall edge states are localized at the square corners, characterized by the linearly crossing one-dimensional band profile. And they can be shifted between the adjacent corners by simply rotating the magnetic field. PMID- 27195482 TI - Nonequilibrium Enhances Adaptation Efficiency of Stochastic Biochemical Systems. AB - Adaptation is a crucial biological function possessed by many sensory systems. Early work has shown that some influential equilibrium models can achieve accurate adaptation. However, recent studies indicate that there are close relationships between adaptation and nonequilibrium. In this paper, we provide an explanation of these two seemingly contradictory results based on Markov models with relatively simple networks. We show that as the nonequilibrium driving becomes stronger, the system under consideration will undergo a phase transition along a fixed direction: from non-adaptation to simple adaptation then to oscillatory adaptation, while the transition in the opposite direction is forbidden. This indicates that although adaptation may be observed in equilibrium systems, it tends to occur in systems far away from equilibrium. In addition, we find that nonequilibrium will improve the performance of adaptation by enhancing the adaptation efficiency. All these results provide a deeper insight into the connection between adaptation and nonequilibrium. Finally, we use a more complicated network model of bacterial chemotaxis to validate the main results of this paper. PMID- 27195484 TI - Robotic action acquisition with cognitive biases in coarse-grained state space. AB - Some of the authors have previously proposed a cognitively inspired reinforcement learning architecture (LS-Q) that mimics cognitive biases in humans. LS-Q adaptively learns under uniform, coarse-grained state division and performs well without parameter tuning in a giant-swing robot task. However, these results were shown only in simulations. In this study, we test the validity of the LS-Q implemented in a robot in a real environment. In addition, we analyze the learning process to elucidate the mechanism by which the LS-Q adaptively learns under the partially observable environment. We argue that the LS-Q may be a versatile reinforcement learning architecture, which is, despite its simplicity, easily applicable and does not require well-prepared settings. PMID- 27195485 TI - The Obesity Paradox and Mortality After Colorectal Cancer: A Causal Conundrum. PMID- 27195486 TI - Impact of Management on Avian Communities in the Scottish Highlands. AB - The protection of biodiversity is a key national and international policy objective. While protected areas provide one approach, a major challenge lies in understanding how the conservation of biodiversity can be achieved in the context of multiple land management objectives in the wider countryside. Here we analyse metrics of bird diversity in the Scottish uplands in relation to land management types and explore how bird species composition varies in relation to land managed for grazing, hunting and conservation. Birds were surveyed on the heather moorland areas of 26 different landholdings in Scotland. The results indicate that, in relation to dominant management type, the composition of bird species varies but measures of diversity and species richness do not. Intensive management for grouse shooting affects the occurrence, absolute and relative abundance of bird species. While less intensive forms of land management appear to only affect the relative abundance of species, though extensive sheep grazing appears to have little effect on avian community composition. Therefore enhanced biodiversity at the landscape level is likely to be achieved by maintaining heterogeneity in land management among land management units. This result should be taken into account when developing policies that consider how to achieve enhanced biodiversity outside protected areas, in the context of other legitimate land-uses. PMID- 27195487 TI - A role for loop G in the beta1 strand in GABAA receptor activation. AB - KEY POINTS: The role of the beta1 strand in GABAA receptor function is unclear. It lies anti-parallel to the beta2 strand, which is known to participate in receptor activation. Molecular dynamics simulation revealed solvent accessible residues within the beta1 strand of the GABAA beta3 homopentamer that might be amenable to analysis using the substituted Cys accessibility method. Cys substitutions from Asp43 to Thr47 in the GABAA alpha1 subunit showed that D43C and T47C reduced the apparent potency of GABA. F45C caused a biphasic GABA concentration-response relationship and increased spontaneous gating. Cys43 and Cys47 were accessible to 2-aminoethyl methanethiosulphonate (MTSEA) modification, whereas Cys45 was not. Both GABA and the allosteric agonist propofol reduced MTSEA modification of Cys43 and Cys47. By contrast, modification of Cys64 in the beta2 strand loop D was impeded by GABA but unaffected by propofol. These data reveal movement of beta1 strand loop G residues during agonist activation of the GABAA receptor. ABSTRACT: The GABAA receptor alpha subunit beta1 strand runs anti parallel to the beta2 strand, which contains loop D, known to participate in receptor activation and agonist binding. However, a role for the beta1 strand has yet to be established. We used molecular dynamics simulation to quantify the solvent accessible surface area (SASA) of beta1 strand residues in the GABAA beta3 homopentamer structure. Residues in the complementary interface equivalent to those between Asp43 and Thr47 in the alpha1 subunit have an alternating pattern of high and low SASA consistent with a beta strand structure. We investigated the functional role of these beta1 strand residues in the alpha1 subunit by individually replacing them with Cys residues. D43C and T47C substitutions reduced the apparent potency of GABA at alpha1beta2gamma2 receptors by 50-fold and eight-fold, respectively, whereas the F45C substitution caused a biphasic GABA concentration-response relationship and increased spontaneous gating. Receptors with D43C or T47C substitutions were sensitive to 2-aminoethyl methanethiosulphonate (MTSEA) modification. However, GABA-evoked currents mediated by alpha1(F45C)beta2gamma2 receptors were unaffected by MTSEA, suggesting that this residue is inaccessible. Both GABA and the allosteric agonist propofol reduced MTSEA modification of alpha1(D43C)beta2gamma2 and alpha1(T47C)beta2gamma2 receptors, indicating movement of the beta1 strand even during allosteric activation. This is in contrast to alpha1(F64C)beta2gamma2 receptors, where only GABA, but not propofol, reduced MTSEA modification. These findings provide the first functional evidence for movement of the beta1 strand during gating of the receptor and identify residues that are critical for maintaining GABAA receptor function. PMID- 27195489 TI - Overwintering of Rabies Virus in Silver Haired Bats (Lasionycteris noctivagans). AB - Silver-haired bats, (Lasionycteris noctivagans) are semi-colonial, migratory tree bats that have infrequent contact with humans. Despite the species rarity, the L. noctivagans rabies variant is the most commonly reported rabies virus variant (RABV) in domestically acquired human rabies cases in the US. Unlike big brown bats (Eptesicus fuscus) and little brown bats (Myotis lucifugus), L. noctivagans are not considered true hibernators. It is unknown if RABV can overwinter in hibernating L. noctivagans or is only maintained in members of this taxa that migrate to warmer climates. To better understand RABV overwintering in this species, L. noctivagans were inoculated intramuscularly with either a homologous RABV (L. noctivagans Virus 1) or one of two heterologous RABV (Eptesicus fuscus Virus 2 and Myotis lucifugus Virus 1). Five days following inoculation, L. noctivagans were placed in a hibernation chamber for 6 weeks. Our results demonstrate that rabies virus can overwinter in L. noctivagans yet the incubation period was extended 6 weeks when compared to bats maintained at ambient temperatures. Additionally, we found that the longer the incubation period, the greater the viral dissemination to the salivary glands. Similar to our previous studies, L. noctivagans were most susceptible to a homologous variant. In summary, we found that RABV incubation is extended following a subcutaneous exposure or maintenance in hibernation and longer incubation times increase dissemination and potential for transmission. PMID- 27195488 TI - A Point-Scoring System for the Clinical Diagnosis of Sjogren's Syndrome Based on Quantified SPECT Imaging of Salivary Gland. AB - OBJECTIVE: To establish a point-scoring diagnostic system for Sjogren's syndrome (SS) based on quantified SPECT imaging of salivary gland, and evaluate its feasibility and performance compared with 2002 AECG criteria and 2012 ACR criteria. METHODS: 213 patients with suspected SS enrolled in this study. The related clinical data of all patients were collected. All patients were evaluated and grouped on a clinical basis and posttreatment follow-up by rheumatology specialists as the unified standard (SS group with 149 cases and nSS group with 64 cases). From SPECT imaging of salivary gland, Tmax, UImax, Ts and EFs were derived for bilateral parotid and submandibular glands, and compared between the groups. A point-scoring diagnostic system for SS was established based on the quantified SPECT imaging of salivary gland. We estimated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy for the new diagnostic system, compared with 2002 AECG criteria and 2012 ACR criteria. RESULTS: When 7.0 was used as the cut-off point, the sensitivity, specificity, PPV, NPV and accuracy for the new point-scoring system in diagnosing SS were 89.93% (134/149), 93.75% (60/64), 97.10% (134/138), 80.00% (60/75) and 91.08% (194/213), respectively. The new point-scoring diagnostic system based on quantified SPECT imaging of salivary gland keeps the specificity comparatively to 2002 AECG criteria and 2012 ACR criteria, but improves the sensitivity significantly (P<0.01). CONCLUSION: The new point-scoring diagnostic system for SS based on quantified SPECT imaging of salivary gland may be superior to 2002 AECG criteria and 2012 ACR criteria, with higher sensitivity and similar specificity in the diagnosis of SS. Additionally, it also has good feasibility in the clinical settings. PMID- 27195490 TI - Dispersion-Energy-Driven Wagner-Meerwein Rearrangements in Oligosilanes. AB - The installation of structural complex oligosilanes from linear starting materials by Lewis acid induced skeletal rearrangement reactions was studied under stable ion conditions. The produced cations were fully characterized by multinuclear NMR spectroscopy at low temperature, and the reaction course was studied by substitution experiments. The results of density functional theory calculations indicate the decisive role of attractive dispersion forces between neighboring trimethylsilyl groups for product formation in these rearrangement reactions. These attractive dispersion interactions control the course of Wagner Meerwein rearrangements in oligosilanes, in contrast to the classical rearrangement in hydrocarbon systems, which are dominated by electronic substituent effects such as resonance and hyperconjugation. PMID- 27195492 TI - Correction: Accuracy of Genomic Selection in a Rice Synthetic Population Developed for Recurrent Selection Breeding. AB - [This corrects the article DOI: 10.1371/journal.pone.0136594.]. PMID- 27195493 TI - Understanding the Spatial Scale of Genetic Connectivity at Sea: Unique Insights from a Land Fish and a Meta-Analysis. AB - Quantifying the spatial scale of population connectivity is important for understanding the evolutionary potential of ecologically divergent populations and for designing conservation strategies to preserve those populations. For marine organisms like fish, the spatial scale of connectivity is generally set by a pelagic larval phase. This has complicated past estimates of connectivity because detailed information on larval movements are difficult to obtain. Genetic approaches provide a tractable alternative and have the added benefit of estimating directly the reproductive isolation of populations. In this study, we leveraged empirical estimates of genetic differentiation among populations with simulations and a meta-analysis to provide a general estimate of the spatial scale of genetic connectivity in marine environments. We used neutral genetic markers to first quantify the genetic differentiation of ecologically-isolated adult populations of a land dwelling fish, the Pacific leaping blenny (Alticus arnoldorum), where marine larval dispersal is the only probable means of connectivity among populations. We then compared these estimates to simulations of a range of marine dispersal scenarios and to collated FST and distance data from the literature for marine fish across diverse spatial scales. We found genetic connectivity at sea was extensive among marine populations and in the case of A. arnoldorum, apparently little affected by the presence of ecological barriers. We estimated that ~5000 km (with broad confidence intervals ranging from 810-11,692 km) was the spatial scale at which evolutionarily meaningful barriers to gene flow start to occur at sea, although substantially shorter distances are also possible for some taxa. In general, however, such a large estimate of connectivity has important implications for the evolutionary and conservation potential of many marine fish communities. PMID- 27195491 TI - A Syntenic Cross Species Aneuploidy Genetic Screen Links RCAN1 Expression to beta Cell Mitochondrial Dysfunction in Type 2 Diabetes. AB - Type 2 diabetes (T2D) is a complex metabolic disease associated with obesity, insulin resistance and hypoinsulinemia due to pancreatic beta-cell dysfunction. Reduced mitochondrial function is thought to be central to beta-cell dysfunction. Mitochondrial dysfunction and reduced insulin secretion are also observed in beta cells of humans with the most common human genetic disorder, Down syndrome (DS, Trisomy 21). To identify regions of chromosome 21 that may be associated with perturbed glucose homeostasis we profiled the glycaemic status of different DS mouse models. The Ts65Dn and Dp16 DS mouse lines were hyperglycemic, while Tc1 and Ts1Rhr mice were not, providing us with a region of chromosome 21 containing genes that cause hyperglycemia. We then examined whether any of these genes were upregulated in a set of ~5,000 gene expression changes we had identified in a large gene expression analysis of human T2D beta-cells. This approach produced a single gene, RCAN1, as a candidate gene linking hyperglycemia and functional changes in T2D beta-cells. Further investigations demonstrated that RCAN1 methylation is reduced in human T2D islets at multiple sites, correlating with increased expression. RCAN1 protein expression was also increased in db/db mouse islets and in human and mouse islets exposed to high glucose. Mice overexpressing RCAN1 had reduced in vivo glucose-stimulated insulin secretion and their beta cells displayed mitochondrial dysfunction including hyperpolarised membrane potential, reduced oxidative phosphorylation and low ATP production. This lack of beta-cell ATP had functional consequences by negatively affecting both glucose stimulated membrane depolarisation and ATP-dependent insulin granule exocytosis. Thus, from amongst the myriad of gene expression changes occurring in T2D beta cells where we had little knowledge of which changes cause beta-cell dysfunction, we applied a trisomy 21 screening approach which linked RCAN1 to beta-cell mitochondrial dysfunction in T2D. PMID- 27195495 TI - PredHSP: Sequence Based Proteome-Wide Heat Shock Protein Prediction and Classification Tool to Unlock the Stress Biology. AB - Heat shock proteins are chaperonic proteins, which are present in every domain of life. They play a crucial role in folding/unfolding of proteins, their sorting and assembly into multi-protein complex, cell cycle control and also protect the cell during stress. Considering the fact that no web-based predictor is available for simultaneous prediction and classification of HSPs, it is imperative to develop a method, which can predict and classify them efficiently. In this study, we have developed coupled amino acid composition and support vector machine based two-tier method, PredHSP that identifies heat shock proteins (1st tier) and classifies it to different families (at 2nd tier). At 1st tier, we achieved maximum accuracy 76.66% with MCC 0.43, while at 2nd tier we achieved maximum accuracy 96.36% with MCC 0.87 for HSP20, 91.91% with MCC 0.83 for HSP40, 95.96% with MCC 0.72 for HSP60, 91.87% with MCC 0.71 for HSP70, 98.43% with MCC 0.70 for HSP90 and 97.48% with MCC 0.71 for HSP100. We have also developed a webserver, as well as standalone package for the use of scientific community, which can be accessed at http://14.139.227.92/mkumar/predhsp/index.html. PMID- 27195496 TI - Positive Attitudes towards Non-Invasive Prenatal Testing (NIPT) in a Swedish Cohort of 1,003 Pregnant Women. AB - OBJECTIVE: The clinical utilization of non-invasive prenatal testing (NIPT) for identification of fetal aneuploidies is expanding worldwide. The aim of this study was to gain an increased understanding of pregnant women's awareness, attitudes, preferences for risk information and decision-making concerning prenatal examinations with emphasis on NIPT, before its introduction into Swedish healthcare. METHOD: Pregnant women were recruited to fill in a questionnaire, including multiple-choice questions and Likert scales, at nine maternity clinics located in different areas of Stockholm, Sweden. RESULTS: In total, 1,003 women participated in the study (86% consent rate). The vast majority (90.7%) considered examinations aiming to detect fetal abnormalities to be good. Regarding NIPT, 59.8% stated that they had heard about the method previously, yet 74.0% would like to use the test if available. The main factor affecting the women's decision to undergo prenatal chromosomal screening was worry about the baby's health (82.5%), followed by the urge to have as much information as possible about the fetus (54.5%). Most women (79.9%) preferred to receive NIPT information orally. CONCLUSION: The overwhelming majority of a cohort of 1,003 pregnant women considered prenatal examinations good. Moreover, the majority had a positive attitude towards NIPT and would like to use the test if available. PMID- 27195494 TI - Receptor Interacting Protein 3-Mediated Necroptosis Promotes Lipopolysaccharide Induced Inflammation and Acute Respiratory Distress Syndrome in Mice. AB - Necrosis amplifies inflammation and plays important roles in acute respiratory distress syndrome (ARDS). Necroptosis is a newly identified programmed necrosis that is mediated by receptor interacting protein 3 (RIP3). However, the potential involvement and impact of necroptosis in lipopolysaccharide (LPS)-induced ARDS remains unknown. We therefore explored the role and mechanism of RIP3-mediated necroptosis in LPS-induced ARDS. Mice were instilled with increasing doses of LPS intratracheally to induce different degrees of ARDS. Lung tissues were harvested for histological and TUNEL staining and western blot for RIP3, p-RIP3, X-linked inhibitor of apoptosis protein (XIAP), mixed lineage kinase domain-like protein (MLKL), total and cleaved caspases-3/8. Then, wild-type and RIP3 knock-out mice were induced ARDS with 30 mg/kg LPS. Pulmonary cellular necrosis was labeled by the propidium Iodide (PI) staining. Levels of TNF-a, Interleukin (IL)-1beta, IL 6, IL-1alpha, IL-10 and HMGB1, tissue myeloperoxidase (MPO) activity, neutrophil counts and total protein concentration were measured. Results showed that in high dose LPS (30mg/kg and 40mg/kg) -induced severe ARDS, RIP3 protein was increased significantly, accompanied by increases of p-RIP3 and MLKL, while in low dose LPS (10mg/kg and 20mg/kg) -induced mild ARDS, apoptosis was remarkably increased. In LPS-induced severe ARDS, RIP3 knock-out alleviated the hypothermia symptom, increased survival rate and ameliorated the lung tissue injury RIP3 depletion also attenuated LPS-induced increase in IL-1alpha/beta, IL-6 and HMGB1 release, decreased tissue MPO activity, and reduced neutrophil influx and total protein concentration in BALF in severe ARDS. Further, RIP3 depletion reduced the necrotic cells in the lung and decreased the expression of MLKL, but had no impact on cleaved caspase-3 in LPS-induced ARDS. It is concluded that RIP3 mediated necroptosis is a major mechanism of enhanced inflammation and lung tissue injury in high dose LPS- induced severe ARDS in mice. PMID- 27195497 TI - Effects of Land-Use Conversion from Double Rice Cropping to Vegetables on Methane and Nitrous Oxide Fluxes in Southern China. AB - Compared with CO2, methane (CH4) and nitrous oxide (N2O) are potent greenhouse gases in terms of their global warming potentials. Previous studies have indicated that land-use conversion has a significant impact on greenhouse gas emissions. However, little is known regarding the impact of converting rice (Oryza sativa L.) to vegetable fields, an increasing trend in land-use change in southern China, on CH4 and N2O fluxes. The effects of converting double rice cropping to vegetables on CH4 and N2O fluxes were examined using a static chamber method in southern China from July 2012 to July 2013. The results indicate that CH4 fluxes could reach 31.6 mg C m-2 h-1 under rice before land conversion. The cumulative CH4 emissions for fertilized and unfertilized rice were 348.9 and 321.0 kg C ha-1 yr-1, respectively. After the land conversion, the cumulative CH4 emissions were -0.4 and 1.4 kg C ha-1 yr-1 for the fertilized and unfertilized vegetable fields, respectively. Similarly, the cumulative N2O fluxes under rice were 1.27 and 0.56 kg N ha-1 yr-1 for the fertilized and unfertilized treatments before the land conversion and 19.2 and 8.5 kg N ha-1 yr-1, respectively, after the land conversion. By combining the global warming potentials (GWPs) of both gases, the overall land-use conversion effect was minor (P = 0.36) with fertilization, but the conversion reduced GWP by 63% when rice and vegetables were not fertilized. Increase in CH4 emissions increased GWP under rice compared with vegetables with non-fertilization, but increased N2O emissions compensated for similar GWPs with fertilization under rice and vegetables. PMID- 27195498 TI - The Corticofugal Effects of Auditory Cortex Microstimulation on Auditory Nerve and Superior Olivary Complex Responses Are Mediated via Alpha-9 Nicotinic Receptor Subunit. AB - BACKGROUND AND OBJECTIVE: The auditory efferent system is a complex network of descending pathways, which mainly originate in the primary auditory cortex and are directed to several auditory subcortical nuclei. These descending pathways are connected to olivocochlear neurons, which in turn make synapses with auditory nerve neurons and outer hair cells (OHC) of the cochlea. The olivocochlear function can be studied using contralateral acoustic stimulation, which suppresses auditory nerve and cochlear responses. In the present work, we tested the proposal that the corticofugal effects that modulate the strength of the olivocochlear reflex on auditory nerve responses are produced through cholinergic synapses between medial olivocochlear (MOC) neurons and OHCs via alpha-9/10 nicotinic receptors. METHODS: We used wild type (WT) and alpha-9 nicotinic receptor knock-out (KO) mice, which lack cholinergic transmission between MOC neurons and OHC, to record auditory cortex evoked potentials and to evaluate the consequences of auditory cortex electrical microstimulation in the effects produced by contralateral acoustic stimulation on auditory brainstem responses (ABR). RESULTS: Auditory cortex evoked potentials at 15 kHz were similar in WT and KO mice. We found that auditory cortex microstimulation produces an enhancement of contralateral noise suppression of ABR waves I and III in WT mice but not in KO mice. On the other hand, corticofugal modulations of wave V amplitudes were significant in both genotypes. CONCLUSION: These findings show that the corticofugal modulation of contralateral acoustic suppressions of auditory nerve (ABR wave I) and superior olivary complex (ABR wave III) responses are mediated through MOC synapses. PMID- 27195510 TI - Structures of androgen receptor bound with ligands: advancing understanding of biological functions and drug discovery. AB - INTRODUCTION: Androgen receptor (AR) is a ligand-dependent transcription factor and a member of the nuclear receptor superfamily. It plays a vital role in male sexual development and regulates gene expression in various tissues, including prostate. Androgens are compounds that exert their biological effects via interaction with AR. Binding of androgens to AR initiates conformational changes in AR that affect binding of co-regulator proteins and DNA. AR agonists and antagonists are widely used in a variety of clinical applications (i.e. hypogonadism and prostate cancer therapy). AREAS COVERED: This review provides a close look at structures of AR-ligand complexes and mutations in the receptor that have been revealed, discusses current challenges in the field, and sheds light on future directions. EXPERT OPINION: AR is one of the primary targets for the treatment of prostate cancer, as AR antagonists inhibit prostate cancer growth. However, these drugs are not effective for long-term treatment and lead to castration-resistant prostate cancer. The structures of AR-ligand complexes are an invaluable scientific asset that enhances our understanding of biological functions and mechanisms of androgenic and anti-androgenic chemicals as well as promotes the discovery of superior drug candidates. PMID- 27195499 TI - Prediction of Mobility Limitations after Hospitalization in Older Medical Patients by Simple Measures of Physical Performance Obtained at Admission to the Emergency Department. AB - OBJECTIVE: Mobility limitations relate to dependency in older adults. Identification of older patients with mobility limitations after hospital discharge may help stratify treatment and could potentially counteract dependency seen in older adults after hospitalization. We investigated the ability of four physical performance measures administered at hospital admission to identify older medical patients who manifest mobility limitations 30 days after discharge. DESIGN: Prospective cohort study of patients (>=65 years) admitted to the emergency department for acute medical illness. During the first 24 hours, we assessed: handgrip strength, 4-meter gait speed, the ability to rise from a chair (chair-stand), and the Cumulated Ambulation Score. The mobility level 30 days after discharge was evaluated using the de Morton Mobility Index. RESULTS: A total of 369 patients (77.9 years, 62% women) were included. Of those, 128 (40%) patients had mobility limitations at follow-up. Univariate analyzes showed that each of the physical performance measures was strongly associated with mobility limitations at follow-up (handgrip strength(women), OR 0.86 (0.81-0.91), handgrip strength(men), OR 0.90 (0.86-0.95), gait speed, OR 0.35 (0.26-0.46), chair-stand, OR 0.04 (0.02-0.08) and Cumulated Ambulation Score OR 0.49 (0.38-0.64). Adjustment for potential confounders did not change the results and the associations were not modified by any of the covariates: age, gender, cognitive status, the severity of the acute medical illness, and the Charlson Comorbidity Index. Based on prespecified cut-offs the prognostic accuracy of the four measures for mobility limitation at follow-up was calculated. The sensitivity and specificity were: handgrip strength(women), 56.8 (45.8-67.3), 75.7 (66.8-83.2), handgrip strength(men), 50.0 (33.8-66.2), 80.8 (69.9-89.1), gait speed, 68.4 (58.2-77.4), 81.4 (75.0-86.8), chair-stand 67.8 (58.6-76.1), 91.8 (86.8-95.3), and Cumulated Ambulation Score, 40.2 (31.6-49.2), 92.0 (87.1-95.4), respectively. CONCLUSION: Physical performance measures, particularly chair-stand and gait speed assessed at admission to an emergency department, were able to identify mobility limitation in acutely admitted older medical patients 30 days after hospital discharge. PMID- 27195511 TI - The effect of exercise training with an additional inspiratory load on inspiratory muscle fatigue and time-trial performance. AB - The purpose was to determine the effect of moderate-intensity exercise training (ET) on inspiratory muscle fatigue (IMF) and if an additional inspiratory load during ET (ET+IL) would further improve inspiratory muscle strength, IMF, and time-trial performance. 15 subjects were randomly divided to ET (n=8) and ET+IL groups (n=7). All subjects completed six weeks of exercise training three days/week at ~70%VO2peak for 30min. The ET+IL group breathed through an inspiratory muscle trainer (15% PImax) during exercise. 5-mile, and 30-min time trials were performed pre-training, weeks three and six. Inspiratory muscle strength increased (p<0.05) for both groups to a similar (p>0.05) extent. ET and ET+IL groups improved (p<0.05) 5-mile time-trial performance (~10% and ~18%) and the ET+IL group was significantly faster than ET at week 6. ET and ET+IL groups experienced less (p<0.05) IMF compared to pre-training following the 5-mile time trial. In conclusion, these data suggest ET leads to less IMF, ET+IL improves inspiratory muscle strength and IMF, but not different than ET alone. PMID- 27195512 TI - Correction: Perioperative Care and the Importance of Continuous Quality Improvement-A Controlled Intervention Study in Three Tanzanian Hospitals. AB - [This corrects the article DOI: 10.1371/journal.pone.0136156.]. PMID- 27195513 TI - Clinical features of bipolar spectrum with binge eating behaviour. AB - OBJECTIVE: To determine whether bipolar spectrum disorder with binge eating behavior (BE) is an important clinical sub-phenotype. METHODS: Prevalence rates and correlates of different levels of BE were assessed in 1114 bipolar spectrum patients participating in a genetic biobank. BE and eating disorders (EDs) were assessed with the Eating Disorder Diagnostic Scale (EDDS). Psychiatric illness burden was evaluated with measures of suicidality, psychosis, mood instability, anxiety disorder comorbidity, and substance abuse comorbidity. Medical illness burden was evaluated with body mass index (BMI) and the Cumulative Index Rating Scale (CIRS). RESULTS: Thirty percent of patients had any BE and 27% had BE plus an ED diagnosis. Compared with bipolar spectrum patients without BE, bipolar spectrum patients with BE were younger and more likely to be female; had significantly higher levels of eating psychopathology, suicidality, mood instability, and anxiety disorder comorbidity; had a significantly higher mean BMI and a significantly higher rate of obesity; and had a significantly higher medical illness burden. Bipolar spectrum patients with BE but no ED diagnosis were more similar to bipolar spectrum patients without BE than to those with an ED. Nonetheless, the positive predictive value and specificity of BE predicting an ED was 0.90 and 0.96, respectively. LIMITATIONS: As only two patients had co occurring anorexia nervosa, these results may not generalize to bipolar spectrum patients with restricting EDs. CONCLUSION: Bipolar spectrum disorder with broadly defined BE may not be as clinically relevant a sub-phenotype as bipolar spectrum disorder with an ED but may be an adequate proxy for the latter when phenotyping large samples of individuals. PMID- 27195514 TI - Neuropsychiatric symptoms in Alzheimer's disease (AD): How sensitive, how prevalent? PMID- 27195515 TI - P600 alteration of syntactic language processing in patients with bipolar mania: Comparison to schizophrenic patients and healthy subjects. AB - BACKGROUND: Disturbances in thought, speech, and linguistic processing are frequently observed in bipolar manic patients, but the underlying neurophysiological mechanisms are not well understood. P600 is a distinct, positive event-related potential component elicited by syntactic violations. Using the P600 ERP, we examined neural processing of syntactic language comprehension in patients with bipolar mania compared to patients with schizophrenia and healthy people. METHOD: P600s were recorded from 21 manic patients with bipolar disorder, 26 patients with schizophrenia, and 29 healthy subjects during the presentation of 120 auditory sentences with syntactic violations or non-violations. Subjects were asked to judge whether each sentence was correct or incorrect. RESULTS: Patients with mania and schizophrenia had significantly smaller P600 amplitudes associated with syntactic violations compared with healthy subjects. There was no difference in P600 amplitude between patient groups. For behavioral performance, patients with schizophrenia had significantly less accurate rates and longer reaction times compared with healthy subjects, whereas manic patients exhibited no significant differences in accuracy and only showed increased reaction times in comparison with healthy subjects. LIMITATIONS: Psychotropic drug usage and small sample size. CONCLUSION: Patients with bipolar mania have reduced P600 amplitude, comparable to patients with schizophrenia. Our findings may represent the first neurophysiological evidence of abnormal syntactic linguistic processing in bipolar mania. PMID- 27195516 TI - Psychometric properties of the Overall Anxiety Severity and Impairment Scale (OASIS) among psychiatric outpatients. AB - BACKGROUND: The Overall Anxiety Severity and Impairment Scale (OASIS) is a brief, transdiagnostic measure used to assess anxiety severity and related interference. The OASIS has demonstrated strong psychometric properties in previous investigations, however, it has yet to be validated using a transdiagnostic clinician-rated measure. METHODS: We evaluated the factor structure, convergent and discriminant validity, and illness severity cut-scores of the OASIS in a sample of outpatients (N=202). RESULTS: A confirmatory factor analysis indicated an unidimensional structure provided the best fit. The OASIS demonstrated good convergent validity and internal consistency. Using the Clinical Global Impression-Severity Scale (CGI-S), ROC curves showed OASIS scores of 6, 10 and 12 to indicate moderate, marked and severe illness severity, respectively. CONCLUSIONS: The OASIS is a unidimensional self-report measure with good convergent validity and data from the current study provide illness severity cut scores. PMID- 27195517 TI - Effects of Facilitated Bacterial Dispersal on the Degradation and Emission of a Desorbing Contaminant. AB - The quantitative relationship between a compound's availability for biological removal and ecotoxicity is a key issue for retrospective risk assessment and remediation approaches. Here, we investigated the impact of facilitated bacterial dispersal at a model soil-atmosphere interface on the release, degradation, and outgassing of a semivolatile contaminant. We designed a laboratory microcosm with passive dosing of phenanthrene (PHE) to a model soil-atmosphere interface (agar surface) in the presence and absence of glass fibers known to facilitate the dispersal of PHE-degrading Pseudomonas fluorescens LP6a. We observed that glass fibers (used as a model to mimic a fungal hyphal network) resulted in (i) increased bacterial surface coverage, (ii) effective degradation of matrix-bound PHE, and (iii) substantially reduced PHE emission to locations beyond the contamination zone even at low bacterial surface coverage. Our data suggest that bacterial dispersal networks such as mycelia promote the optimized spatial arrangement of microbial populations to allow for effective contaminant degradation and reduction of potential hazard to organisms beyond a contaminated zone. PMID- 27195518 TI - The mitogenome of a 35,000-year-old Homo sapiens from Europe supports a Palaeolithic back-migration to Africa. AB - After the dispersal of modern humans (Homo sapiens) Out of Africa, hominins with a similar morphology to that of present-day humans initiated the gradual demographic expansion into Eurasia. The mitogenome (33-fold coverage) of the Pestera Muierii 1 individual (PM1) from Romania (35 ky cal BP) we present in this article corresponds fully to Homo sapiens, whilst exhibiting a mosaic of morphological features related to both modern humans and Neandertals. We have identified the PM1 mitogenome as a basal haplogroup U6*, not previously found in any ancient or present-day humans. The derived U6 haplotypes are predominantly found in present-day North-Western African populations. Concomitantly, those found in Europe have been attributed to recent gene-flow from North Africa. The presence of the basal haplogroup U6* in South East Europe (Romania) at 35 ky BP confirms a Eurasian origin of the U6 mitochondrial lineage. Consequently, we propose that the PM1 lineage is an offshoot to South East Europe that can be traced to the Early Upper Paleolithic back migration from Western Asia to North Africa, during which the U6 lineage diversified, until the emergence of the present-day U6 African lineages. PMID- 27195519 TI - Vertically aligned nanostructured TiO2 photoelectrodes for high efficiency perovskite solar cells via a block copolymer template approach. AB - We fabricated perovskite solar cells with enhanced device efficiency based on vertically oriented TiO2 nanostructures using a nanoporous template of block copolymers (BCPs). The dimension and shape controllability of the nanopores of the BCP template allowed for the construction of one-dimensional (1-D) TiO2 nanorods and two-dimensional (2-D) TiO2 nanowalls. The TiO2 nanorod-based perovskite solar cells showed a more efficient charge separation and a lower charge recombination, leading to better performance compared to TiO2 nanowall based solar cells. The best solar cells employing 1-D TiO2 nanorods showed an efficiency of 15.5% with VOC = 1.02 V, JSC = 20.0 mA cm(-2) and fill factor = 76.1%. Thus, TiO2 nanostructures fabricated from BCP nanotemplates could be applied to the preparation of electron transport layers for improving the efficiency of perovskite solar cells. PMID- 27195520 TI - Complex infrapopliteal revascularization in elderly patients with critical limb ischemia: impact of multidisciplinary integrated care on mid-term outcome. AB - BACKGROUND: The incidence of critical limb ischemia (CLI) is exponentially rising among our aging population. There is a paucity of scientific evidence on best management and clinical outcome of infra-popliteal (IP) revascularizations in elderly CLI patients. METHODS: A prospectively collected database was analyzed to identify consecutive octogenarian and nonagenarian patients who underwent IP revascularizations (bypass or angioplasty) for CLI (Rutherford 4-6) in a single center between 2010-2014. The primary end points were overall amputation-free survival (AFS) and overall survival (OS) at 1 and 2 years. Secondary endpoints were primary, assisted-primary, secondary patency and limb-salvage (LS) rates by Kaplan-Meier analysis. Univariate and multivariate analysis was performed to find factors predicting outcome. RESULTS: A total of 129 limbs in 120 patients were treated with IP bypass (N.=42) and endovascular (N.=87) revascularizations with a mean age of 85(+/-5) years. The overall primary patency, assisted-primary patency and secondary patency were 58%, 65% and 70%, respectively at 12 months and 34%, 48% and 59% at 24 months. Primary, assisted-primary and secondary patency analyzed by treatment method (endovascular vs. bypass) was 54% vs. 52%, 61% vs. 70%, 69% vs. 75% at 1 year and 21% vs. 36%, 24% vs. 62%, 31% vs. 72% at 2 years. The overall AFS at 12 and 24 months was 62% and 46% respectively; AFS was 71%-68% in the bypass group and 53-21% in the Endovascular group (P<0.001). LS was 89% at 12 months and 84% at 24 months, with no significant difference between the bypass and endovascular groups (P=0.24). The overall perioperative mortality rate was 2%. OS by Kaplan-Meier was 68% and 54% at 1 and 2 years respectively. Diabetes (P=0.046) and low eGFR (P=0.041) were predictors of worse AFS and OS, respectively. CONCLUSIONS: IP revascularizations (either endovascular or surgical) is feasible and effective in octogenarians and nonagenarians with CLI. By adopting a patient-tailored approach, both revascularizations strategies have satisfactory technical and clinical outcomes in this high-risk group. Subgroup analysis suggests that bypass surgery may have better mid-term secondary patency and AFS rates. PMID- 27195521 TI - Selective effects of a fiber chimeric conditionally replicative adenovirus armed with hep27 gene on renal cancer cell. AB - ASBTARCT Adenoviruses mediated cancer gene therapies are widely investigated and show a promising effect on cancer treatment. However, efficient gene transfer varies among different cancer cell lines based on the expression of coxsakie adenovirus receptor (CAR). Hep27, a member of dehydrogenase/reductase (SDR) family, can bind to Mdm2, resulting in the attenuation of Mdm2-mediated p53 degradation. Here we constructed a fiber chimeric adenovirus carrying hep27 gene (F5/35-ZD55-Hep27), in which the fiber protein of 5-serotype adenovirus (Ad5) was substituted by that of 35-serotype adenovirus (Ad35), aiming to facilitate the infection for renal cancer cells and develop the role of hep27 in cancer therapy. We evaluated the CAR and CD46 (a membrane cofactor protein for Ad35) expression in four kinds of renal cancer cells and assessed the relationship between receptors and infection efficiency. 5/35 fiber-modified adenovirus had a much promising infectivity compared with Ad5-based vector in renal cancer cells. F5/35 ZD55-Hep27 had enhanced antitumor activity against human renal cancer cells compared to the other groups. Further, hep27 mediated p53 and cleaved-PARP upregulation and mdm2 downregulation was involved and caused increased apoptosis. Moreover, F5/35-ZD55-Hep27 significantly suppressed tumor growth in subcutaneous renal cancer cell xenograft models. Our data demonstrated that 5/35 fiber modified adenovirus F5/35-ZD55-Hep27 transferred into renal cancers efficiently and increased p53 to induce cancer cell apoptosis. Thus 5/35 fiber-modified adenoviral vector F5/35-ZD55-Hep27 might a promising vector and antitumor reagent for renal cancer gene therapy. PMID- 27195524 TI - Reduction of Surgical Complications in Dogs and Cats by the Use of a Surgical Safety Checklist. AB - OBJECTIVE: To examine whether the use of a surgical safety checklist (SSC) could reduce the incidence of complications after small animal surgery. STUDY DESIGN: Prospective clinical study. ANIMALS: Client-owned dogs and cats (n = 520). METHODS: Consecutive cases were enrolled in the study, the first 300 cases without implementation of the surgical checklist (SSC-), followed by 220 cases with implementation of the checklist (SSC+). The checklist was adapted from the WHO surgical checklist and consisted of three different check points: (1) before induction of anaesthesia (sign in), (2) before surgical incision (time out), and (3) before recovery (sign out). In-hospital outcomes were prospectively recorded, and complications within 6 weeks were retrospectively recorded by reviewing medical records and by telephone interviews with owners. The severity of each recorded complication was graded as minor, moderate, or severe. Comparisons were made between SSC- and SSC+ outcomes. RESULTS: There were significantly more complications in SSC- animals than SSC+ animals (SSC- 52/300 vs. SSC+ 15/220, P = .0003). There was a significantly higher frequency of SSI (P = .045) and wound healing complications (P = .0006) for SSC- animals than SSC+ animals. CONCLUSION: The frequency and severity of postoperative complications was significantly decreased after introduction of a surgical checklist. All veterinary hospitals should consider using a surgical checklist. Compliance with implementation of the checklist is important for success. PMID- 27195525 TI - Immobilization of a rhodium catalyst using a diphosphine-functionalized ionic liquid in RTIL for the efficient and recyclable biphasic hydroformylation of 1 octene. AB - A highly efficient and stable Rh-P catalytic system in the RTIL of [PEmim]BF4 was developed for the biphasic hydroformylation of 1-octene by using the diphosphine functionalized ionic liquid (FIL) of 2. While 2-Rh(acac)(CO)2 was immobilized in [PEmim]BF4 (solvent), a typical biphasic catalysis was fulfilled with advantages of facile separation and recycling ability - 9 runs without any loss of activity. It was found that not only the acquired pi-acceptor character of 2, but also the synergetic role of the piperidyl group in [PEmim]BF4 as an N-containing donor, cooperatively contributed to the efficient hydroformylation due to the facilitated formation and stability of the Rh-H active species (nu 2045 cm(-1)). This was supported by the in situ high-pressure FT-IR spectral analysis. PMID- 27195523 TI - Activation in the Right Inferior Parietal Lobule Reflects the Representation of Musical Structure beyond Simple Pitch Discrimination. AB - Pitch discrimination tasks typically engage the superior temporal gyrus and the right inferior frontal gyrus. It is currently unclear whether these regions are equally involved in the processing of incongruous notes in melodies, which requires the representation of musical structure (tonality) in addition to pitch discrimination. To this aim, 14 participants completed two tasks while undergoing functional magnetic resonance imaging, one in which they had to identify a pitch change in a series of non-melodic repeating tones and a second in which they had to identify an incongruous note in a tonal melody. In both tasks, the deviants activated the right superior temporal gyrus. A contrast between deviants in the melodic task and deviants in the non-melodic task (melodic > non-melodic) revealed additional activity in the right inferior parietal lobule. Activation in the inferior parietal lobule likely represents processes related to the maintenance of tonal pitch structure in working memory during pitch discrimination. PMID- 27195522 TI - Transcriptional profiling of the mouse hippocampus supports an NMDAR-mediated neurotoxic mode of action for benzo[a]pyrene. AB - Benzo[a]pyrene (BaP) is a genotoxic carcinogen and a neurotoxicant. The neurotoxicity of BaP is proposed to arise from either genotoxicity leading to neuronal cell death, or perturbed expression of N-methyl-d-aspartate receptor (NMDAR) subunits. To explore these hypotheses, we profiled hippocampal gene expression of adult male Muta(TM) Mouse administered 0, 1, 35, or 70 mg BaP/kg bw per day by oral gavage for 3 days. Transcriptional profiles were examined by RNA sequencing (RNA-seq), DNA microarrays, and real-time quantitative reverse transcription polymerase chain reaction (RT-PCR). BaP-DNA adducts in the cerebellum were quantified by (32) P-post-labeling to measure genotoxicity. RNA seq revealed altered expression of 0, 260, and 219 genes (P-value < 0.05, fold change >= +/- 1.5) following exposure to the low, medium, and high doses, respectively; 54 genes were confirmed by microarrays. Microarray and RT-PCR analysis showed increased expression of NMDAR subunits Grina and Grin2a. In contrast, no effects on DNA-damage response genes were observed despite comparable BaP-DNA adduct levels in the cerebellum and in the lungs and livers of mice at similar BaP doses in previous studies. The results suggest that DNA damage response does not play a major role in BaP-induced adult neurotoxicity. Meta-analysis revealed that BaP-induced transcriptional profiles are highly correlated with those from the hippocampus of transgenic mice exhibiting similar neurotoxicity outcomes to BaP-exposed mice and rats (i.e., defects in learning and memory). Overall, we suggest that BaP-induced neurotoxicity is more likely to be a consequence of NMDAR perturbation than genotoxicity, and identify other important genes potentially mediating this adverse outcome. Environ. Mol. Mutagen. 57:350-363, 2016. (c) 2016 Her Majesty the Queen in Right of Canada. Environmental and Molecular Mutagenesis (c) 2016 Environmental Mutagen Society. PMID- 27195527 TI - Pregnancy affects nevirapine pharmacokinetics: evidence from a CYP2B6 genotype guided observational study. AB - OBJECTIVES: Previous studies on nevirapine pharmacokinetics during pregnancy reported contradictory findings. METHODS: The magnitude of pregnancy-induced changes in nevirapine pharmacokinetics was investigated in a genotype-guided study preceded by a pharmacogenetic association study of six genes involved in its disposition. RESULTS: CYP2B6 516 G>T and 983 T>C were associated independently with plasma nevirapine concentrations in pregnant (n=110) and postpartum (n=122) women and were used for stratification. NR1I3 540C>T and P450 oxidoreductase 1508C>T were associated with lower and higher plasma concentrations in pregnant and postpartum women, respectively. In the intensive pharmacokinetic phase, apparent clearance (CL/F) was higher in pregnant (n=31) than postpartum (n=28) women (P=0.022) and AUC0-12, Cmax and Cmin were significantly lower. When stratified on the basis of composite CYP2B6 516 G>T and 983 T>C genotypes, CL/F was similar between pregnant (n=6) and postpartum (n=9) women with no variant alleles, but Cmin was below target (3400 ng/ml) in most patients in both groups. In women with one variant allele, clearance was 40.6% higher (P=0.0009) and Cmin was below target in 58% (11/19) of pregnant and 0% (0/10) of postpartum women. Similarly, clearance was 51.7% higher (P=0.008) in pregnant compared with postpartum women with two variant alleles. Cmin was below target in 50% (3/6) of pregnant and 0% (0/10) of postpartum women. CONCLUSION: Nevirapine exposure is significantly reduced during pregnancy. The pharmacodynamic consequences in patients at risk of suboptimal exposure and potential dose optimization strategies warrant further investigation. PMID- 27195529 TI - Utilizing in Situ Electrochemical SHINERS for Oxygen Reduction Reaction Studies in Aprotic Electrolytes. AB - Spectroscopic detection of reaction intermediates upon a variety of electrode surfaces is of major interest within physical chemistry. A notable technique in the study of the electrochemical interface has been surface-enhanced Raman spectroscopy (SERS). The drawback of SERS is that it is limited to roughened gold and silver substrates. Herein we report that shell-isolated nanoparticles for enhanced Raman spectroscopy (SHINERS) can overcome the limitations of SERS and has followed the oxygen reduction reaction (ORR), within a nonaqueous electrolyte, on glassy carbon, gold, palladium, and platinum disk electrodes. The work presented demonstrates SHINERS for spectroelectrochemical studies for applied and fundamental electrochemistry in aprotic electrolytes, especially for the understanding and development of future metal-oxygen battery applications. In particular, we highlight that with the addition of Li(+), both the electrode surface and solvent influence the ORR mechanism, which opens up the possibility of tailoring surfaces to produce desired reaction pathways. PMID- 27195526 TI - Challenges of Identifying Clinically Actionable Genetic Variants for Precision Medicine. AB - Advances in genomic medicine have the potential to change the way we treat human disease, but translating these advances into reality for improving healthcare outcomes depends essentially on our ability to discover disease- and/or drug associated clinically actionable genetic mutations. Integration and manipulation of diverse genomic data and comprehensive electronic health records (EHRs) on a big data infrastructure can provide an efficient and effective way to identify clinically actionable genetic variants for personalized treatments and reduce healthcare costs. We review bioinformatics processing of next-generation sequencing (NGS) data, bioinformatics infrastructures for implementing precision medicine, and bioinformatics approaches for identifying clinically actionable genetic variants using high-throughput NGS data and EHRs. PMID- 27195528 TI - HLA-B*57: 01 genotyping in the prevention of hypersensitivity to abacavir: 5 years of experience. AB - INTRODUCTION: Most of the cost-effectiveness analyses are based on estimations to make decisions on the future implementation of a test. However, the model should be verified with real data to prove that previous estimations have been successfully fulfilled. OBJECTIVE: To study the economic impact of the systematic HLA-B*57:01 genotyping in preventing hypersensitivity reactions (HSRs) in the patient population of a tertiary-care hospital treated with abacavir (ABC) using retrospective data of 5 years of experience. METHODS: A retrospective study was carried out with two cohorts including 780 and 473 patients before and after the implementation of the systematic HLA-B*57:01 genotyping before ABC treatment. Cost-effectiveness analysis was carried out by the parameter 'cost per HSR avoided'. The clinical utility of the test was verified by evaluating the differences in HSR incidence between both cohorts. Finally, a sensitivity analysis including all variables was carried out. RESULTS: In the population studied, systematic genotyping represents an additional cost of &OV0556;306 per HSR avoided. In the sensitivity analysis, pharmacological therapy cost is the major influencing factor found in the estimation of the 'cost per HSR avoided'. In terms of clinical utility, the incidence ratio was 0.040 (95% confidence interval 0.0009-0.2399) and statistically significant differences were found between both groups (P=1.40*10). CONCLUSION: Retrospective data from 5 years of experience have confirmed the cost-effectiveness of the systematic genotyping in candidate patients for ABC therapy, and have shown that cost-effectiveness is a dynamic parameter closely linked to allele prevalence and pharmacological therapy costs. PMID- 27195530 TI - Effectiveness of a social robot, "Paro," in a VA long-term care setting. AB - Interest in animal assisted interventions (AAI) has grown over the years, but acceptance of AAI by the clinical and research community has been hampered by safety, hygiene, and logistical concerns. Advances in the field of social robotics have provided a promising route to deliver AAI while avoiding these aforementioned obstacles. Although there has been promising initial research on social robotics in older adults, to date there has been no such research conducted with a veteran population. The present pilot study followed 23 veteran residents of a Veterans Affairs (VA) geropsychiatric long-term care facility over the span of approximately a year and a half. It was found that use of Paro, a social robot, resulted in increased observed positive affective and behavioral indicators, with concomitant decreases observed in negative affective and behavioral indicators. The authors concluded that Paro is likely an effective nonpharmacological approach for managing dementia-related mood and behavior problems with veterans in VA long term care facilities. They additionally observed that Paro is best presented to residents who are relatively calm and approachable, as opposed to actively exhibiting behavior or mood problems. Future research directions are discussed in light of both the positive results noted and the inherent limitations of our pilot study. (PsycINFO Database Record PMID- 27195531 TI - Stabilized Heptapeptide A7R for Enhanced Multifunctional Liposome-Based Tumor Targeted Drug Delivery. AB - (L)A7R (ATWLPPR) is a heptapeptide with high binding affinity in vitro to vascular endothelial growth factor receptor 2 (VEGFR2) and neuropilin-1 (NRP-1) overexpressed on glioma, glioma vasculogenic mimicry and neovasculature. However, its tumor targeting efficacy is significantly reduced in vivo due to proteolysis in blood circulation. To improve the in vivo stability and targeting efficacy, the retro inverso isomer of (L)A7R ((D)A7R) was developed for glioma-targeted drug delivery. (D)A7R was expected to have a similar binding affinity to its receptors in vitro (VEGFR2 and NRP-1), which was experimentally confirmed. In vivo, (D)A7R-modified liposomes achieved improved glioma-targeted efficiency than did (L)A7R-modified liposomes. After loading a chemotherapeutic agent (doxorubicin), (D)A7R-modified liposomes significantly inhibited subcutaneous model tumor in comparison to free doxorubicin, plain liposomes and (L)A7R modified liposomes. In summary, the present study presented the potential of a proteolytically stable d-peptide ligand for in vivo tumor-targeted drug delivery. PMID- 27195532 TI - Imidacloprid Exposure Suppresses Neural Crest Cells Generation during Early Chick Embryo Development. AB - Imidacloprid is a neonicotinoid pesticide that is widely used in the control pests found on crops and fleas on pets. However, it is still unclear whether imidacloprid exposure could affect early embryo development-despite some studies having been conducted on the gametes. In this study, we demonstrated that imidacloprid exposure could lead to abnormal craniofacial osteogenesis in the developing chick embryo. Cranial neural crest cells (NCCs) are the progenitor cells of the chick cranial skull. We found that the imidacloprid exposure retards the development of gastrulating chick embryos. HNK-1, PAX7, and Ap-2alpha immunohistological stainings indicated that cranial NCCs generation was inhibited after imidacloprid exposure. Double immunofluorescent staining (Ap-2alpha and PHIS3 or PAX7 and c-Caspase3) revealed that imidacloprid exposure inhibited both NCC proliferation and apoptosis. In addition, it inhibited NCCs production by repressing Msx1 and BMP4 expression in the developing neural tube and by altering expression of EMT-related adhesion molecules (Cad6B, E-Cadherin, and N-cadherin) in the developing neural crests. We also determined that imidacloprid exposure suppressed cranial NCCs migration and their ability to differentiate. In sum, we have provided experimental evidence that imidacloprid exposure during embryogenesis disrupts NCCs development, which in turn causes defective cranial bone development. PMID- 27195533 TI - Prevalence, treatment and control of hypertension in La Reunion: the REDIA population-based cohort study. AB - A better knowledge of prevalence, management and determinants of hypertension is needed in regions in epidemiological transition to adapt the strategies of public health screening and prevention, and to reduce the burden of cardiovascular diseases. We conducted a prospective cohort study including 4610 participants aged between 18 and 69 years and representative of the general population of La Reunion, a French overseas island located in the western Indian Ocean. The median time between inclusion and follow-up was 7.4 years. Blood pressure data at baseline and follow-up of 3087 participants were analyzed. We found a high prevalence of hypertension, especially in women (36.7% [34.5-39.0]) and in men (40.3% [37.6-43.0]) and in the under 30s (17.1% [14.0-20.5]), with an increase of 10% at follow-up. Treatment rates were very low in men (19.5% versus 39.1% in women) as was awareness of their condition (25.7% versus 44.6%). Blood pressure control rates were similar (18% at baseline and 34% at follow-up for both sexes). Diagnosis of hypertension at follow-up among subjects normotensive at baseline was independently associated with obesity at baseline (relative risk (RR) = 1.40 [1.12-1.75] for BMI between 27 and 30 kg/m2 and 1.72 [1.33-2.25] for BMI >=30 kg/m2 as compared with BMI <27 kg/m2) and HbA1C (RR =1.12 [1.05-1.19] per %), suggesting a prominent role of insulin resistance in our population. Our study provides original data that cannot be assimilated to any existing model and should guide the implementation of original community-based programs in such countries. PMID- 27195580 TI - Metallosupramolecular Coordination Complexes: The Design of Heterometallic 3d-4f Gridlike Structures. AB - A series of mixed metal 3d-4f gridlike structures, [Dy4(H2L')4Zn4(SCN)4] (1) and [Dy4(H2L')4Mx(SCN)8] (Mx = Co3 (2); Mx = Cu5 (3)), showing Chinese hieroglyph like [2 * 2], [3 * 2], and [3 * 3] matrixes, were assembled and magnetically characterized. Remarkably, the empty cage constructed by the oblique organic ligands and SCN(-) ions in complex 1 were filled with the large inorganic ions [Co3(SCN)4](2+) and [Cu5(SCN)4](6+) in complexes 2 and 3, respectively, forming the first [3 * 2] and [3 * 3] 3d-4f gridlike structures. Additionally, magnetic studies show that complex 1 exhibits field-induced SMM behavior and double magnetic relaxation, while complexes 2 and 3 display typical SMM behavior at zero applied field. PMID- 27195581 TI - Controllable Cooperative Self-Assembly of PS-b-PAA/PS-b-P4VP Mixture by Tuning the Intercorona Interaction. AB - The cooperative self-assembly of amphiphilic polystyrene-block-poly(acrylic acid) (PS144-b-PAA22) and polystyrene-block-poly(4-vinylpyridine) (PS144-b-P4VP33) diblock copolymers in DMF/H2O mixtures has been investigated. Both copolymers self-assemble into small spherical micelles (SSMs) if used individually. However, the equimolar mixture of these two copolymers cooperatively self-assembles into vesicles. It is found that the formation of vesicles is attributed to the complex interactions between PAA and P4VP chains, including the hydrogen bonds between un ionized acrylic acid units and pyridine units as well as the electronic attractions between ionized acrylic acid units and protonated pyridine units. Since these interactions between PAA and P4VP chains depend on pH value, the cooperatively self-assembled morphology can be easily tuned by the addition of HCl or NaOH. At high addition of H(+) or OH(-), the intercorona interaction is repulsive and the copolymer mixture tends to form SSMs (basic condition) or cylindrical micelles (acidic condition), whereas it prefers to aggregate into vesicles at low addition of H(+) or OH(-) because the intercorona interaction is attractive. Interestingly, the same morphology of the self-assembled aggregates can be obtained either at high H(+) addition or at low OH(-) addition, which results from the nonmonotonic variation of the intercorona interaction along with the addition of HCl or NaOH. The current study implies that it is the intercorona interaction rather than the chemical condition that dominates the cooperatively self-assembled morphology. PMID- 27195582 TI - Synergistic Effects in Bimetallic Palladium-Copper Catalysts Improve Selectivity in Oxygenate Coupling Reactions. AB - Condensation reactions such as Guerbet and aldol are important since they allow for C-C bond formation and give higher molecular weight oxygenates. An initial study identified Pd-supported on hydrotalcite as an active catalyst for the transformation, although this catalyst showed extensive undesirable decarbonylation. A catalyst containing Pd and Cu in a 3:1 ratio dramatically decreased decarbonylation, while preserving the high catalytic rates seen with Pd based catalysts. A combination of XRD, EXAFS, TEM, and CO chemisorption and TPD revealed the formation of CuPd bimetallic nanoparticles with a Cu-enriched surface. Finally, density functional theory studies suggest that the surface segregation of Cu atoms in the bimetallic alloy catalyst produces Cu sites with increased reactivity, while the Pd sites responsible for unselective decarbonylation pathways are selectively poisoned by CO. PMID- 27195592 TI - The Relationship Between Occupation Transition Status and Metabolic Syndrome in Adult Women: Tehran Lipid and Glucose Study. AB - PURPOSE: Although occupation status may play a role in the risk of metabolic syndrome (MetS), data on this topic are limited. The aim was to examine the association between occupation transition status and the 12-year incidence of MetS in adult women of a population-based cohort study. METHODS: A total of 2406 women, aged >=20 years, were selected from the Tehran Lipid and Glucose Study. Subjects were free of MetS at baseline and followed for a mean of 12 years. Based on occupation transition from baseline to the end of follow-up, women were classified into four groups: employed-employed (group I), employed-unemployed (group II), unemployed-employed (group III), and unemployed-unemployed (group IV). The odds ratio (OR) for the occurrence of MetS and its components according to occupation transition status was assessed by multivariate logistic regression. RESULTS: The incidence of MetS in group I and group IV was 15.6% and 29.3%, respectively. In comparison with women in group I, those in group IV had higher risk of MetS (OR = 2.45, 95% CI, 1.6-3.8); however, after adjustment for age, education level, marital status, smoking, and body mass index, the association between occupation status and MetS was not significant (OR = 1.38, 95% CI, 0.83 2.27). In the fully adjusted model, women who were employed at baseline and unemployed at the end of follow-up had greater risk of incident MetS (OR = 2.26, 95% CI, 1.26-4.06) and low high-density lipoprotein cholesterol (OR = 2.34, 95% CI, 1.40-3.85) compared with those who were constantly employed. CONCLUSION: Occupation transition from employed to unemployed status was found to increase risk of incident MetS. PMID- 27195593 TI - Primary Gonadal Insufficiency in Male and Female Childhood Cancer Survivors in a Long-Term Follow-Up Clinic. AB - PURPOSE: Childhood cancer survivors (CCS) are at increased risk of primary gonadal insufficiency (PGI). This study evaluated the prevalence and clinical characteristics of PGI in CCS. METHODS: In this single-center, retrospective, observational, longitudinal study, we characterized CCS with PGI attending the oncology Long-Term Follow-Up (LTFU) Clinic at an Australian university hospital (January 2012-August 2014). From a cohort of 276 CCS, 54 (32 males) met criteria for PGI: elevated gonadotropins plus low estradiol/amenorrhoea (females) or low testosterone/small testicles for age (males). RESULTS: Median age at primary diagnosis was 4.8 years (inter-quartile range [IQR] 3.0-9.7 years) and at LTFU, it was 22.3 years (IQR 18.2-25.7 years). Fifty-three participants (98.1%) were treated with known highly gonadotoxic therapies: alkylating chemotherapy (96.3%), radiotherapy (70.3%), total body irradiation (29.6%), bone marrow transplantation (51.9%), or multimodal protocols (68.5%). At primary diagnosis, 86.7% participants were Tanner stage I and at LTFU, 89.1% participants were Tanner stage V. More females (95.5%; n = 21) than males (40.6%; n = 13) were treated with hormone development therapy (HDT) (p < 0.01). Of these, more than half (n = 18; 7 males) required pubertal induction. There was no significant difference in serum luteinizing hormone/follicle stimulating hormone (LH/FSH), testosterone/estradiol between those untreated and those treated with HDT. Among those on HDT, 60.7% had persistently elevated FSH+/-LH and 33.3% had low testosterone or estradiol. Six males had semen analysis (five azoospermic, one oligospermic). Psychological assessment was documented in 61.1% of participants, and two-thirds reported fertility concerns. CONCLUSION: PGI is an evolving phenotype that is common in CCS. Suboptimal treatment and non-adherence occur frequently. Ongoing assessment is essential to ensure prompt diagnosis, adequate intervention and to promote HDT adherence. PMID- 27195594 TI - Strategies to overcome acquired resistances conferred by mutations in the kinase domain of EGFR. AB - Deregulation of EGFR is involved in the development of many cancers. The inhibition of EGFR kinase activity has been clinically validated as a promising approach for the treatment of non-small-cell lung cancer (NSCLC). However, all NSCLC patients who initially benefited from first-generation EGFR inhibitors eventually develop drug resistance. A point mutation at the gatekeeper position, T790M in EGFR kinase domain accounts for more than 50% of acquired resistance. Therefore, second- and third-generation EGFR inhibitors have been developed to overcome the resistance conferred by the gatekeeper mutation. This review has highlighted recent advances in overcoming acquired resistance for the development of each generation of EGFR inhibitors along with their potential issues, and urgent quest for the development of new generation of EGFR inhibitors. PMID- 27195595 TI - Do Carolina chickadees (Poecile carolinensis) and tufted titmice (Baeolophus bicolor) attend to the head or body orientation of a perched avian predator? AB - Individuals of many prey species adjust their foraging behavior in response to the presence of a predator. Responding to predators takes time away from searching for and exploiting food resources. To balance between the need to avoid predation and the need to forage, individuals should attend to cues from predators that indicate risk. Two such cues might be the predator's head orientation (where it might be looking) and body orientation (where it might be moving). In the current study, flocks of Carolina chickadees, Poecile carolinensis, and tufted titmice, Baeolophus bicolor, were presented with perched hawk and owl models. Predator model head and body orientation were independently manipulated relative to a feeding station birds were using. Chickadees and titmice avoided the feeders more when the heads of the models were facing toward the feeders compared to facing away from the feeders. Calling behavior of birds was also affected by head orientation of the models. No effect of predator body orientation on chickadee and titmouse behavior was detected. The results indicate that when chickadees and titmice detect a perched avian predator, they assess risk primarily based upon its head orientation. (PsycINFO Database Record PMID- 27195598 TI - Out-of-plane spin polarization of edge currents in Chern insulator with Rashba spin-orbit interaction. AB - We investigate the change in the non-zero Chern number and out-of-plane spin polarization of the edge currents in a honeycomb lattice with the Haldane-Rashba interaction. This interaction breaks the time-reversal symmetry due to the Haldane phase caused by a current loop at the site-I and site-II atoms, and also accounts for the Rashba-type spin-orbit interaction. The Rashba spin-orbit interaction increases the number of Dirac points and the band-touching phenomenon can be generated by tuning the on-site potential in the non-zero Haldane phase. By using the Pontryagin winding number and numerical Berry curvature methods, we find that the Chern number pattern is {+2, -1, 0} and {-2, +1, 0} for the positive and negative Haldane phase, respectively. A non-zero Chern number is called a Chern-insulating phase. We discovered that changes in both the Haldane phase and on-site potential leads to a change in the orientation of the bulk spin polarization of site-I and site-II atoms. Interestingly, in a ribbon with a zigzag edge, which naturally has site-I atoms at one outer edge and site-II atoms at the opposite outer edge, the spin polarization of the edge states approximately obeys the properties of bulk spin polarization regardless of the change in the Chern number. In addition, even when the Chern number changes from +2 to -1 (or -2 to +1), by tuning the strength of the on-site potential, the sign of the spin polarization of the edge states persists. This approximate bulk edge correspondence of the spin polarization in the Haldane-Rashba system would play an important role in spintronics, because it enables us to control the orientation of the spin polarization in a single Chern-insulating phase. PMID- 27195597 TI - The burden of COPD mortality due to ambient air pollution in Guangzhou, China. AB - Few studies have investigated the chronic obstructive pulmonary disease (COPD) mortality fraction attributable to air pollution and modification by individual characteristics of air pollution effects. We applied distributed lag non-linear models to assess the associations between air pollution and COPD mortality in 2007-2011 in Guangzhou, China, and the total COPD mortality fraction attributable to air pollution was calculated as well. We found that an increase of 10 MUg/m(3) in particulate matter with an aerodynamic diameter of 10 MUm or less (PM10), sulfur dioxide (SO2) and nitrogen dioxide (NO2) was associated with a 1.58% (95% confidence interval (CI): 0.12-3.06%), 3.45% (95% CI: 1.30-5.66%) and 2.35% (95% CI: 0.42-4.32%) increase of COPD mortality over a lag of 0-15 days, respectively. Greater air pollution effects were observed in the elderly, males and residents with low educational attainment. The results showed 10.91% (95% CI: 1.02-9.58%), 12.71% (95% CI: 5.03-19.85%) and 13.38% (95% CI: 2.67-22.84%) COPD mortality was attributable to current PM10, SO2 and NO2 exposure, respectively. In conclusion, the associations between air pollution and COPD mortality differed by individual characteristics. There were remarkable COPD mortality burdens attributable to air pollution in Guangzhou. PMID- 27195599 TI - An Adolescent Male With a "Knot" in His Neck. PMID- 27195600 TI - Comparison of Febrile Infants With Enterococcal and Gram-negative Urinary Tract Infections. AB - BACKGROUND: Few data exist on the presentations and clinical courses of infants with enterococcal urinary tract infections (UTI). The objective of this study was to compare the clinical presentation, sensitivity of urinalysis (UA) and Gram's stain, radiological abnormalities and adverse events of febrile infants with enterococcal UTIs to those with Gram-negative UTIs. METHODS: Retrospective study of febrile (>=38.0 degrees C) infants 29-60 days of age with UTIs at 20 emergency departments. UTI was defined as growth of (1) >=50,000 colony forming units (CFUs)/mL of a single pathogen; or (2) either 10,000 to <50,000 CFUs/mL or 10,000 100,000 CFUs/mL (depending on laboratory reporting) with a positive UA or Gram's stain. RESULTS: Thirty-seven (2.0%) of 1870 infants with febrile UTIs had enterococcal UTIs. On bivariable analysis, infants with enterococcal UTIs more frequently had histories of prematurity, previous hospitalizations, histories of genitourinary abnormalities, previous UTIs and ill-appearance in the emergency department compared with infants with Gram-negative UTIs (all P <0.05). On multivariable analysis, >= grade 3 vesicoureteral reflux (adjusted odds ratio 3.2, 95% confidence interval: 1.4, 7.6) and hydronephrosis (adjusted odds ratio 3.3, 95% confidence interval: 1.4, 7.9) were associated with enterococcal UTIs. Both groups had similar low risks of adverse events or severe clinical courses. The urine white blood cell count alone or in combination with leukocyte esterase was more sensitive for Gram-negative than enterococcal UTIs (range 80.4%-93.9% vs. 50.0%-75.9%). CONCLUSIONS: Febrile infants with enterococcal UTIs had a low likelihood of adverse events or severe clinical course, similar to those with Gram-negative UTIs. Infants with enterococcal UTIs frequently had underlying hydronephrosis and/or vesicoureteral reflux. The preliminary diagnosis of enterococcal UTIs may be inaccurate if based on UA. PMID- 27195601 TI - Vaccination Timeliness in Children Under India's Universal Immunization Program. AB - BACKGROUND: India has the highest number of deaths among children younger than 5 years of age globally; the majority are from vaccine preventable diseases. Untimely vaccination unnecessarily prolongs susceptibility to disease and contributes to the burden of childhood morbidity and mortality, yet there is scarce literature on vaccination delays. The aim of this study is to characterize the timeliness of childhood vaccinations administered under India's routine immunization program using a novel application of an existing statistical methodology. METHODS: This study utilized the district level household and facility survey data, 2008 from India using vaccination data from children with and without immunization cards. Turnbull estimator of the cumulative distribution function was used to estimate the probability of vaccination at each age. Timeliness of Bacille Calmette-Guerin (BCG), all 3 doses of diphtheria, pertussis and tetanus vaccine (DPT) and measles-containing vaccine (MCV) were considered for this analysis. RESULTS: Vaccination data on 268,553 children who were 0-60 months of age were analyzed; timely administration of BCG, DPT3 and MCV occurred in 31%, 19% and 34% of children, respectively. The estimated vaccination probability plateaued for DPT and BCG around the age of 24 months, whereas MCV uptake increased another 5% after 24 months of age. The 5-year coverage of BCG, DPT3 and MCV in Indian children was 87%, 63% and 76%, respectively. CONCLUSIONS: Lack of timely administration of key childhood vaccines, especially DPT3 and MCV, remains a major challenge in India and likely contributes to the significant burden of vaccine preventable disease-related morbidity and mortality in children. PMID- 27195602 TI - Providing Safe and Effective Preventative Antiretroviral Prophylaxis to HIV exposed Newborns via a Novel Drug Delivery System in Tanzania. AB - BACKGROUND: In developing countries, antiretroviral therapy provides life-saving treatment to HIV-positive women and their children before, during and after birth. However, supply chain challenges such as long distances, medication shortages and nonfacility deliveries often compromise consistent access to prophylactic treatment for at-risk infants. A proposed intervention to address these challenges, often referred to as the "Pratt Pouch," allows for liquid formulation medications, such as nevirapine (NVP), to be repackaged into single dose pouches. These pouches are distributed antenatally. METHODS: HIV-positive women at Kilimanjaro Christian Medical Centre in Moshi, Tanzania received 14 pouches each containing a single dose of NVP for prevention of mother-to-child transmission. Women were trained on how to open the pouch and dispense the medication to their infants after delivery. All participating women were asked to return to Kilimanjaro Christian Medical Centre 7-14 days after delivery, where infant blood spots were collected to assess NVP levels. RESULTS: All enrolled women (21/21) administered NVP to their infants within 24 hours of birth. All enrolled infants (22/22) had NVP blood concentrations over 100 ng/mL and exhibited no health concerns attributable to over or under dosing. CONCLUSIONS: The Pratt Pouch intervention provides a clinically appropriate solution for addressing liquid-formulation antiretroviral access challenges in developing countries. PMID- 27195603 TI - Clinical Predictors of Sensorineural Hearing Loss and Cognitive Outcome in Infants with Symptomatic Congenital Cytomegalovirus Infection. AB - The objective of this study was to determine newborn clinical findings predictive of adverse clinical outcomes in infants with symptomatic congenital cytomegalovirus infection. Of 160 infants, significantly more children with central nervous system involvement had sensorineural hearing loss (P = 0.0007) and an IQ <=70 (P < 0.0001) compared with infants with transient findings or only a petechial rash. PMID- 27195604 TI - Diarrhea, Urosepsis and Hemolytic Uremic Syndrome Caused by the Same Heteropathogenic Escherichia coli Strain. AB - We describe an 8-month-old girl with diarrhea, urosepsis and hemolytic uremic syndrome caused by Escherichia coli. Typing of cultured E. coli strains from urine and blood revealed the presence of virulence factors from multiple pathotypes of E. coli. This case exemplifies the genome plasticity of E. coli and the resulting heteropathogenic strains. PMID- 27195605 TI - Tandem Bond-Forming Reactions of 1-Alkynyl Ethers. AB - Electron-rich alkynes, such as ynamines, ynamides, and ynol ethers, are functional groups that possess significant potential in organic chemistry for the formation of carbon-carbon bonds. While the synthetic utility of ynamides has recently been expanded considerably, 1-alkynyl ethers, which possess many of the reactivity features of ynamides, have traditionally been far less investigated because of concerns about their stability. Like ynamides, ynol ethers are relatively unhindered to approach by functional groups present in the same or different molecules because of their linear geometry, and they can potentially form up to four new bonds in a single transformation. Ynol ethers also possess unique reactivity features that make them complementary to ynamides. Research over the past decade has shown that ynol ethers formed in situ from stable precursors engage in a variety of useful carbon-carbon bond-forming processes. Upon formation at -78 degrees C, allyl alkynyl ethers undergo a rapid [3,3] sigmatropic rearrangement to form allyl ketene intermediates, which may be trapped with alcohol or amine nucleophiles to form gamma,delta-unsaturated carboxylic acid derivatives. The process is stereospecific, takes place in minutes at cryogenic temperatures, and affords products containing (quaternary) stereogenic carbon atoms. Trapping of the intermediate allyl ketene with carbonyl compounds, epoxides, or oxetanes instead leads to complex alpha-functionalized beta-, gamma-, or delta-lactones, respectively. [3,3]-Sigmatropic rearrangement of benzyl alkynyl ethers also takes place at temperatures ranging from -78 to 60 degrees C to afford substituted 2-indanones via intramolecular carbocyclization of the ketene intermediate. tert-Butyl alkynyl ethers containing pendant di- and trisubstituted alkenes and enol ethers are stable to chromatographic isolation and undergo a retro-ene/[2 + 2] cycloaddition reaction upon mild thermolysis (90 degrees C) to afford cis-fused cyclobutanones and donor-acceptor cyclobutanones in good to excellent yields and diastereoselectivities. This process, which takes place under neutral conditions and proceeds through an aldoketene intermediate, obviates the need to employ moisture-sensitive and/or unstable acid chlorides under basic conditions for intramolecular [2 + 2] cycloaddition reactions. Furthermore, Lewis acid-catalyzed intramolecular condensations of both ethyl and tert-butyl ynol ethers with tethered acetals efficiently provide protected five-, six-, and seven-membered cyclic Baylis-Hilman adducts. Metalated ethoxyacetylene can also participate in multiple bond-forming reactions that avoid isolation of the alkynyl ether intermediate. Lewis acid-promoted tandem additions employing epoxides/oxetanes and carbonyl compounds give rise to (Z)-alpha-alkylidene and alpha-benzylidene lactones stereoselectively in high overall yields. Three new carbon-carbon bonds and a ring are formed in this atom-economical single-flask transformation, resulting in a significant increase in molecular complexity. This Account provides a detailed overview of these useful transformations with the intention of stimulating further interest in and research on ynol ethers and their application in organic synthesis. PMID- 27195606 TI - Using the Integration of Discrete Event and Agent-Based Simulation to Enhance Outpatient Service Quality in an Orthopedic Department. AB - Many hospitals are currently paying more attention to patient satisfaction since it is an important service quality index. Many Asian countries' healthcare systems have a mixed-type registration, accepting both walk-in patients and scheduled patients. This complex registration system causes a long patient waiting time in outpatient clinics. Different approaches have been proposed to reduce the waiting time. This study uses the integration of discrete event simulation (DES) and agent-based simulation (ABS) to improve patient waiting time and is the first attempt to apply this approach to solve this key problem faced by orthopedic departments. From the data collected, patient behaviors are modeled and incorporated into a massive agent-based simulation. The proposed approach is an aid for analyzing and modifying orthopedic department processes, allows us to consider far more details, and provides more reliable results. After applying the proposed approach, the total waiting time of the orthopedic department fell from 1246.39 minutes to 847.21 minutes. Thus, using the correct simulation model significantly reduces patient waiting time in an orthopedic department. PMID- 27195607 TI - Human coronavirus and severe acute respiratory infection in Southern Brazil. AB - Human coronaviruses (HCoVs) are an important cause of respiratory tract infection and are responsible for causing the common cold in the general population. Thus, adequate surveillance of HCoV is essential. This study aimed to analyze the impact of HCoV infections and their relation to severe acute respiratory infection (SARI) in a hospitalized population in Southern Brazil. A cross sectional study was conducted at a tertiary care hospital, and assessed inpatients under investigation for SARI by the hospital epidemiology department, and all patients who had nasopharyngeal aspirates collected from January 2012 to December 2013 to detect respiratory viruses (RVs). Viral infection was detected by multiplex reverse transcriptase polymerase chain reaction (RT-PCR), with primers specific to the subtypes HCoV-229E/NL63 and OC43/HKU1. The overall positivity rate was 58.8% (444/755), and HCoVs were detected in 7.6% (n = 34) of positive samples. Children below two years of age were most frequently affected (62%). Comorbidities were more likely to be associated with HCoVs than with other RVs. Immunosuppression was an independent risk factor for HCoV infection (OR = 3.5, 95% CI 1.6-7.6). Dyspnea was less frequently associated with HCoV infection (p < 0.001), and HCoV accounted for 6% of the SARI cases. Three patients infected with HCoV (9%) died from respiratory infection. HCoVs are important respiratory pathogens, especially in hospitalized children under 2 years of age and in immunosuppressed patients. They may account for a small proportion of SARI diagnoses, increased need for mechanical ventilation, intensive care unit admission, and death. PMID- 27195608 TI - Radiation Sensitivity of Human CD34(+) Cells Versus Peripheral Blood T Lymphocytes of Newborns and Adults: DNA Repair and Mutagenic Effects. AB - As hematopoietic stem and progenitor cells (HSPCs) self-renew throughout life, accumulation of genomic alterations can potentially give rise to radiation carcinogenesis. In this study we examined DNA double-strand break (DSB) induction and repair as well as mutagenic effects of ionizing radiation in CD34(+) cells and T lymphocytes from the umbilical cord of newborns. The age dependence of DNA damage repair end points was investigated by comparing newborn T lymphocytes with adult peripheral blood T lymphocytes. As umbilical cord blood (UCB) contains T lymphocytes that are practically all phenotypically immature, we examined the radiation response of separated naive (CD45RA(+)) and memory (CD45RO(+)) T lymphocytes. The number of DNA DSBs was assessed by microscopic scoring of gamma H2AX/53BP1 foci 0.5 h after low-dose radiation exposure, while DNA repair was studied by scoring the number of residual gamma-H2AX/53BP1 foci 24 h after exposure. Mutagenic effects were studied by the cytokinesis block micronucleus (CBMN) assay. No significant differences in the number of DNA DSBs induced by low dose (100-200 mGy) radiation were observed among the three different cell types. However, residual gamma-H2AX/53BP1 foci levels 24 h postirradiation were significantly lower in CD34(+) cells compared to newborn T lymphocytes, while newborn T lymphocytes showed significantly higher foci yields than adult T lymphocytes. No significant differences in the level of radiation-induced micronuclei at 2 Gy were observed between CD34(+) cells and newborn T lymphocytes. However, newborn T lymphocytes showed a significantly higher number of micronuclei compared to adult T lymphocytes. These results confirm that CD34(+) cell quiescence promotes mutagenesis after exposure. Furthermore, we can conclude that newborn peripheral T lymphocytes are significantly more radiosensitive than adult peripheral T lymphocytes. Using the results from the comparative study of radiation-induced DNA damage repair end points in naive (CD45RA(+)) and memory (CD45RO(+)) T lymphocytes, we could demonstrate that the observed differences between newborn and adult T lymphocytes can be explained by the immunophenotypic change of T lymphocytes with age, which is presumably linked with the remodeling of the closed chromatin structure of naive T lymphocytes. PMID- 27195609 TI - Use of the NASA Space Radiation Laboratory at Brookhaven National Laboratory to Conduct Charged Particle Radiobiology Studies Relevant to Ion Therapy. AB - Although clinical studies with carbon ions have been conducted successfully in Japan and Europe, the limited radiobiological information about charged particles that are heavier than protons remains a significant impediment to exploiting the full potential of particle therapy. There is growing interest in the U.S. to build a cancer treatment facility that utilizes charged particles heavier than protons. Therefore, it is essential that additional radiobiological knowledge be obtained using state-of-the-art technologies and biological models and end points relevant to clinical outcome. Currently, most such ion radiotherapy-related research is being conducted outside the U.S. This article addresses the substantial contributions to that research that are possible at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory (BNL), which is the only facility in the U.S. at this time where heavy-ion radiobiology research with the ion species and energies of interest for therapy can be done. Here, we briefly discuss the relevant facilities at NSRL and how selected charged particle biology research gaps could be addressed using those facilities. PMID- 27195610 TI - Decorporation of Pu/Am Actinides by Chelation Therapy: New Arguments in Favor of an Intracellular Component of DTPA Action. AB - Diethylenetriaminepentaacetic acid (DTPA) is currently still the only known chelating drug that can be used for decorporation of internalized plutonium (Pu) and americium (Am). It is generally assumed that chelation occurs only in biological fluids, thus preventing Pu/Am deposition in target tissues. We postulate that actinide chelation may also occur inside cells by a mechanism called "intracellular chelation". To test this hypothesis, rats were given DTPA either prior to (termed "prophylactic" treatment) or belatedly after (termed "delayed" treatment) Pu/Am injection. DTPA decorporation efficacy was systematically tested for both plutonium and americium. Both prophylactic and delayed DTPA elicited marked decreases in liver Pu/Am. These results can be explained by chelation within subcellular compartments where DTPA efficacy increased as a function of a favorable intracellular DTPA-to-actinide molar ratio. The efficacy of intracellular chelation of liver actinides decreased with the delay of treatment. This is probably explained by progressive actinide binding to the high-affinity ligand ferritin followed by migration to lysosomes. Intracellular chelation was reduced as the gap between prophylactic treatment and contamination increased. This may be explained by the reduction of the intracellular DTPA pool, which declined exponentially with time. Skeletal Pu/Am was also reduced by prophylactic and delayed DTPA treatments. This decorporation of bone actinides may mainly result from extracellular chelation on bone surfaces. This work provides converging evidence for the involvement of an intracellular component of DTPA action in the decorporation process. These results may help to improve the interpretation of biological data from DTPA treated contamination cases and could be useful to model DTPA therapy regimens. PMID- 27195612 TI - A Biospecimen Proficiency Testing Program for Biobank Accreditation: Four Years of Experience. AB - Biobanks produce and distribute biospecimens, ensuring their fitness for purpose and accurately qualifying them before distribution. In their efforts toward professionalization, biobanks can nowadays seek certification or accreditation. One of the requirements of these standards is regular participation in Proficiency Testing (PT) programs. An international PT program has been developed and provided to biobanks and other laboratories that perform specific tests to qualify different types of biospecimens. This PT program includes biospecimen testing schemes, as well as biospecimen processing interlaboratory exercises. This PT program supports the development of biobank quality assurance by providing the possibility to assess biobank laboratory performance and useful insights into biobank laboratory method performance characteristics and thus fulfill the demands from accreditation authorities. PMID- 27195611 TI - Prognostic evaluation of VEGFA genotypes and haplotypes in a cohort of Brazilian women with non metastatic breast cancer. AB - Vascular Endothelial Growth Factor (VEGF) mediates angiogenesis, which is crucial for tumor development and progression. The present study aimed to evaluate the impact of VEGFA gene polymorphisms rs699947, rs833061, rs1570360, rs2010963 and rs3025039 on breast cancer features and prognosis. A cohort of Brazilian women (N = 1038) with unilateral non-metastatic breast cancer was evaluated. The association between VEGFA polymorphisms and histopathological features or pathological complete response (pCR) to neoadjuvant chemotherapy was evaluated by the Chi-square test, with calculation of the respective odds ratio (OR) and 95% confidence intervals (95% CI). The impact of individual categories on disease free survival was evaluated using Kaplan-Meier curves and multivariate Cox proportional hazards regression models for calculation of adjusted hazard ratios (HRadjusted). Variant genotypes of rs699947 (CA + AA) were significantly associated with high-grade (G2 + G3) tumors (OR = 1.82; 95% CI = 1.15 - 2.89), and with shorter disease-free survival among patients treated with neoadjuvant chemotherapy followed by mastectomy (HRadjusted = 1.82; 95% CI = 1.16 - 2.86). Variant genotypes of rs833061 (TC + CC) were significantly associated with high grade (G2 + G3) tumors (OR = 1.79; 95% CI = 1.12 - 2.84) and with positive lymph node status (OR = 1.34; 95% CI = 1.01 - 1.77), but showed no independent effect on disease-free survival. Variant haplotypes (*2 to *5) appear to favor pCR (OR = 7.1; 95% CI = 1.7 - 30.1). VEGFA genotyping may add to prognostic evaluation of breast cancer, with rs699947 being the most likely to contribute. PMID- 27195613 TI - Local anesthetic bupivacaine induced ovarian and prostate cancer apoptotic cell death and underlying mechanisms in vitro. AB - Retrospective studies indicate that the use of regional anesthesia can reduce cancer recurrence after surgery which could be due to ranging from immune function preservation to direct molecular mechanisms. This study was to investigate the effects of bupivacaine on ovarian and prostate cancer cell biology and the underlying molecular mechanisms. Cell viability, proliferation and migration of ovarian carcinoma (SKOV-3) and prostate carcinoma (PC-3) were examined following treatment with bupivacaine. Cleaved caspase 3, 8 and 9, and GSK-3beta, pGSK-3beta(tyr216) and pGSK-3beta(ser9) expression were assessed by immunofluorescence. FAS ligand neutralization, caspase and GSK-3 inhibitors and GSK-3beta siRNA were applied to further explore underlying mechanisms. Clinically relevant concentrations of bupivacaine reduced cell viability and inhibited cellular proliferation and migration in both cell lines. Caspase 8 and 9 inhibition generated partial cell death reversal in SKOV-3, whilst only caspase 9 was effective in PC-3. Bupivacaine increased the phosphorylation of GSK 3beta(Tyr216) in SKOV-3 but without measurable effect in PC3. GSK-3beta inhibition and siRNA gene knockdown decreased bupivacaine induced cell death in SKOV-3 but not in PC3. Our data suggests that bupivacaine has direct 'anti cancer' properties through the activation of intrinsic and extrinsic apoptotic pathways in ovarian cancer but only the intrinsic pathway in prostate cancer. PMID- 27195615 TI - Thank You, Thank You, Thank You. PMID- 27195614 TI - Is the recent emergence of mephedrone injecting in the United Kingdom associated with elevated risk behaviours and blood borne virus infection? AB - The recent, and rapid, emergence of injection of the short-acting stimulant mephedrone (4-methylmethcathione) has resulted in concerns about increased infection risks among people who inject drugs (PWID). Data from the bio behavioural surveillance of PWID in the United Kingdom were analysed to examine the impact of mephedrone injection on infections among PWID. During the year preceding the survey, 8.0% of PWID (163/2,047) had injected mephedrone. In multivariable analyses, those injecting mephedrone were younger, less likely to have injected opiates, and more likely to have injected cocaine or amphetamines, used needle/syringe programmes or sexual health clinics, been recruited in Wales and Northern Ireland or shared needles/syringes. There were no differences in sexual risks. Those injecting mephedrone more often had hepatitis C antibodies (adjusted odds ratio (AOR) = 1.51; 95% confidence interval (CI): 1.08-2.12), human immunodeficiency virus (AOR = 5.43; 95% CI: 1.90-15.5) and overdosed (AOR = 1.70; 95% CI: 1.12-2.57). There were no differences in the frequency of injecting site infections or prevalence of hepatitis B. The elevated levels of risk and infections are a concern considering its recent emergence. Mephedrone injection may currently be focused among higher-risk or more vulnerable groups. Targeted responses are needed to prevent an increase in harm. PMID- 27195616 TI - Perioperative Ultrasound: The Future Is Now. PMID- 27195618 TI - Advancing Perioperative Medicine and Anesthesia Practices into the Era of Digital Quality Improvement. PMID- 27195617 TI - Anesthetic Suppression of Thalamic High-Frequency Oscillations: Evidence that the Thalamus Is More Than Just a Gateway to Consciousness? PMID- 27195619 TI - Show Me the Data! A Perioperative Data Warehouse of Epic Proportions. PMID- 27195620 TI - Big Data: A Cheerleader for Translational Perioperative Medicine. PMID- 27195621 TI - Why a Paper on Anesthesia and Polio in 2016? PMID- 27195622 TI - Airway Assessment Before Intervention: What We Know and What We Do. PMID- 27195623 TI - Postoperative Anemia: A Sign of Treatment Failure. PMID- 27195624 TI - How Can We Best Balance Pain Control and Rehabilitation After Knee Replacement? PMID- 27195625 TI - The Anesthesia Workforce and Levels of Maternal Care. PMID- 27195626 TI - Physician Supervision of Nurse Anesthetists: To Opt In or To Opt Out? PMID- 27195628 TI - Pilots Use Checklists, Why Don't Anesthesiologists? The Future Lies in Resilience. PMID- 27195627 TI - In-Training Clinical Performance Scores Explaining American Board of Anesthesiology Certification: A Step Further. PMID- 27195629 TI - Plagiarism Is Ubiquitous. PMID- 27195630 TI - Perioperative Ultrasound Training in Anesthesiology: A Call to Action. PMID- 27195631 TI - Postoperative Morbidity and Discharge Destinations After Fast-Track Hip and Knee Arthroplasty in Patients Older Than 85 Years. AB - BACKGROUND: Elderly patients are at risk of increased length of hospital stay (LOS), postoperative complications, readmission, and discharge to destinations other than home after elective total hip arthroplasty (THA) and total knee arthroplasty (TKA). Recent studies have found that enhanced recovery protocols or fast-track surgery can be safe for elderly patients undergoing these procedures and may result in reduced LOS. However, detailed studies on preoperative comorbidity and differentiation between medical and surgical postoperative morbidity in elderly patients are scarce. The aim of this study was to provide detailed information on postoperative morbidity resulting in LOS >4 days or readmissions <90 days after fast-track THA and TKA in patients >=85 years. METHODS: This is a descriptive, observational study in consecutive unselected patients >=85 years undergoing fast-track THA/TKA. The primary outcome was the causes of postoperative morbidity leading to an LOS of >4 days. Secondary outcomes were 90-day surgically related readmissions, discharge destination, 90 day mortality, and role of disposing factors for LOS >4 days and 90-day readmissions. Data on preoperative characteristics were prospectively gathered using patient-reported questionnaires. Data on all admissions were collected using the Danish National Health Registry, ensuring complete follow-up. Any cases of LOS >4 days or readmissions were investigated through review of discharge forms or medical records. Backward stepwise logistic regression was used for analysis of association between disposing factors and LOS >4 days and 90-day readmission. RESULTS: Of 13,775 procedures, 549 were performed in 522 patients >=85 years. Median age was 87 years (interquartile range, 85-88) and median LOS of 3 days (interquartile range, 2-5). In 27.3% procedures, LOS was >4 days, with 82.7% due to medical causes, most often related to anemia requiring blood transfusion and mobilization issues. Use of walking aids was associated with LOS >4 days (odds ratio [OR], 1.99; 95% confidence interval [CI], 1.26-3.15; P = 0.003), whereas preoperative anemia showed borderline significance (OR, 1.52; 95% CI, 0.99-2.32; P = 0.057). Thirty-eight patients (6.9%) were not discharged directly home, of which 68.4% had LOS >4 days. Readmission rates were 14.2% and 17.9% within 30 and 90 days, respectively, and 75.5% of readmissions within 90 days were medical, mainly due to falls and suspected but disproved venous thromboembolic events. Preoperative anemia was associated with increased (OR, 1.81; 95% CI, 1.13-2.91; P = 0.014) and living alone with decreased (OR, 0.50; 95% CI, 0.31-0.80; P = 0.004) risk of 90-day readmissions. Ninety-day mortality was 2.0%, with 1.0% occurring during primary admission. CONCLUSIONS: Fast-track THA and TKA with an LOS of median 3 days and discharge to home are feasible in most patients >=85 years. However, further attention to pre- and postoperative anemia and the pathogenesis of medical complications is needed to improve postoperative outcomes and reduce readmissions. PMID- 27195632 TI - Blood Pressure Monitoring for the Anesthesiologist: A Practical Review. AB - Periodic, quantitative measurement of blood pressure (BP) in humans, predating the era of evidence-based medicine by over a century, is a component of the American Society of Anesthesiologists standards for basic anesthetic monitoring and is a staple of anesthetic management worldwide. Adherence to traditional BP parameters complicates the ability of investigators to determine whether particular BP ranges confer any clinical benefits. The BP waveform is a complex amalgamation of both antegrade and retrograde (reflected) pressure waves and is affected by vascular compliance, distance from the left ventricle, and the 3D structure of the vascular tree. Although oscillometry is the standard method of measuring BP semicontinuously in anesthetized patients and is the primary form of measurement in >80% of general anesthetics, major shortcomings of oscillometry are its poor performance at the extremes and its lack of information concerning BP waveform. Although arterial catheterization remains the gold standard for accurate BP measurement, 2 classes of devices have been developed to noninvasively measure the BP waveform continuously, including tonometric and volume clamp devices. Described in terms of a feedback loop, control of BP requires measurement, an algorithm (usually human), and an intervention. This narrative review article discusses the details of BP measurement and the advantages and disadvantages of both noninvasive and invasive monitoring, as well as the principles and algorithms associated with each technique. PMID- 27195633 TI - A Systematic Approach to Creation of a Perioperative Data Warehouse. AB - Extraction of data from the electronic medical record is becoming increasingly important for quality improvement initiatives such as the American Society of Anesthesiologists Perioperative Surgical Home. To meet this need, the authors have built a robust and scalable data mart based on their implementation of EPIC containing data from across the perioperative period. The data mart is structured in such a way so as to first simplify the overall EPIC reporting structure into a series of Base Tables and then create several Reporting Schemas each around a specific concept (operating room cases, obstetrics, hospital admission, etc.), which contain all of the data required for reporting on various metrics. This structure allows centralized definitions with simplified reporting by a large number of individuals who access only the Reporting Schemas. In creating the database, the authors were able to significantly reduce the number of required table identifiers from >10 to 3, as well as to correct errors in linkages affecting up to 18.4% of cases. In addition, the data mart greatly simplified the code required to extract data, making the data accessible to individuals who lacked a strong coding background. Overall, this infrastructure represents a scalable way to successfully report on perioperative EPIC data while standardizing the definitions and improving access for end users. PMID- 27195634 TI - Perioperative Supplemental Oxygen Does Not Worsen Long-Term Mortality of Colorectal Surgery Patients. AB - BACKGROUND: A follow-up analysis from a large trial of oxygen and surgical-site infections reported increased long-term mortality among patients receiving supplemental oxygen, especially those having cancer surgery. Although concerning, there is no obvious mechanism linking oxygen to long-term mortality. We thus tested the hypothesis that supplemental oxygen does not increase long-term mortality in patients undergoing colorectal surgery. Secondarily, we evaluated whether the effect of supplemental oxygen on mortality depended on cancer status. METHODS: Mortality data were obtained for 927 patients who participated in 2 randomized trials evaluating the effect of supplemental oxygen on wound infection. We assessed the effect of 80% vs 30% oxygen on long-term mortality across 4 clinical sites in the 2 trials using a Cox proportional hazards regression model stratified by study and site. Kaplan-Meier survival estimates were calculated for each trial. Finally, we report site-stratified hazard ratios for patients with and without cancer at baseline. RESULTS: There was no effect of 80% vs 30% oxygen on mortality, with an overall site-stratified hazard ratio of 0.93 (95% confidence interval [CI], 0.72-1.20; P = 0.57). The treatment effect was consistent across the 2 original studies (interaction P = 0.88) and across the 4 sites (P = 0.84). There was no difference between patients with (n = 451) and without (n = 450) cancer (interaction P = 0.51), with hazard ratio of 0.85 (95% CI, 0.64-1.1) for cancer patients and 0.97 (0.53-1.8) for noncancer patients. CONCLUSIONS: In contrast to the only previous publication, we found that supplemental oxygen had no influence on long-term mortality in the overall surgical population or in patients having cancer surgery. PMID- 27195636 TI - No Pain Labor & Delivery: A Global Health Initiative's Impact on Clinical Outcomes in China. AB - The availability of labor analgesia is highly variable in the People's Republic of China. There are widespread misconceptions, by both parturients and health care providers, that labor epidural analgesia is harmful to mother and baby. Meanwhile, China has one of the highest cesarean delivery rates in the world, exceeding 50%. The goal of the nongovernmental No Pain Labor & Delivery (NPLD) is to facilitate sustainable increases in vaginal delivery rates by increasing access to safe neuraxial labor analgesia, thereby decreasing the cesarean delivery rate. NPLD was launched in 2008 with the stated goal of improving labor outcome in China by increasing the absolute labor epidural analgesia rate by 10%. NPLD established 10 training centers over a 10-year period. We hypothesized that increased availability of labor analgesia would result in reduced requests for cesarean delivery and better labor outcomes for mother and baby. Multidisciplinary teams of Western clinicians and support staff traveled to China for 8 to 10 days once a year. The approach involved establishing 24/7 obstetric anesthesia coverage in Chinese hospitals through education and modeling multidisciplinary approaches, including problem-based learning discussions, bedside teaching, daily debriefings, simulation training drills, and weekend conferences. As of November 2015, NPLD has engaged with 31 hospitals. At 24 of these sites, 24/7 obstetric anesthesia coverage has been established and labor epidural analgesia rates have exceeded 50%. Lower rates of cesarean delivery, episiotomy, postpartum blood transfusion, and better neonatal outcomes were documented in 3 impact studies comprising approximately 55,000 deliveries. Changes in practice guidelines, medical policy, and billing codes have been implemented in conjunction with the modernization of perinatal practice that has occurred concurrently in China since the first NPLD trip in 2008. PMID- 27195635 TI - Acute Kidney Injury After Abdominal Surgery: Incidence, Risk Factors, and Outcome. AB - BACKGROUND: Acute kidney injury (AKI) is a serious complication after major surgical procedures. We examined the incidence, risk factors, and mortality of patients who sustained AKI after abdominal surgery in a large population-based cohort. METHODS: All patients who underwent open and laparoscopic abdominal surgery (excluding genitourinary and abdominal vascular procedures), between 2007 and 2014 at the University Hospital in Reykjavik were identified and their perioperative serum creatinine (SCr) measurements used to identify AKI after surgery employing the Kidney Disease: Improving Global Outcome (KDIGO) criteria. Risk factors were evaluated using multivariate logistic regression analysis and 30-day mortality compared with a propensity score-matched control group. RESULTS: During the 8-year period, a total of 11,552 abdominal surgeries were performed on 10,022 patients. Both pre- and postoperative SCr measurements were available for 3902 (33.8%) of the surgical cases. Of these, 264 (6.8%) were complicated by AKI; 172 (4.4%), 49 (1.3%), and 43 (1.1%) were classified as KDIGO stages 1, 2 and 3, respectively. The overall incidence of AKI for patients with available SCr values was 67.7 (99% confidence interval [CI], 57.7-78.6) per 1000 surgeries. In logistic regression analysis, independent risk factors for AKI were female sex (odds ratio [OR] = 0.68; 99% CI, 0.47-0.98), hypertension (OR = 1.75; 99% CI, 1.10-2.74), preoperative chronic kidney disease (OR= 1.68; 99% CI, 1.12-2.50), ASA physical status classification of IV (OR = 9.48; 99% CI, 3.66-29.2) or V (OR = 21.4; 99% CI, 5.28-93.6), and reoperation (OR = 4.30; 99% CI, 2.36-7.70). Patients with AKI had greater 30-day mortality (18.2% vs 5.3%; P < 0.001) compared with propensity score-matched controls. CONCLUSIONS: AKI is an important complication of abdominal surgery. In addition to sex, hypertension, and chronic kidney disease, ASA physical status classification is an independent predictor of AKI. Individuals who develop AKI have substantially worse short-term outcomes, including higher 30-day mortality, even after correcting for multiple patient- and procedure-related risk factors. PMID- 27195637 TI - Hospital-Level Factors Associated with Anesthesia-Related Adverse Events in Cesarean Deliveries, New York State, 2009-2011. AB - BACKGROUND: Marked variation across hospitals in adverse maternal outcomes in cesarean deliveries is reported, including anesthesia-related adverse events (ARAEs). Identification of hospital-level characteristics accounting for this variation may help guide interventions to improve anesthesia care quality. In this study, we examined the association between hospital-level characteristics and ARAEs in cesarean deliveries and assessed individual hospital performance. METHODS: Discharge records for cesarean deliveries, ARAEs, and patient characteristics in the State Inpatient Database for New York State 2009 to 2011 were identified with International Classification of Diseases, Ninth Revision, Clinical Modification codes. The hospital reporting index was calculated as the sum of International Classification of Diseases, Ninth Revision, Clinical Modification codes divided by the number of discharges. Data on hospital characteristics were obtained from the American Hospital Association and the Area Health Resources files. Multilevel modeling was used to examine the association of hospital-level characteristics with ARAEs and to assess individual hospital performance. RESULTS: The study included 236,960 discharges indicating cesarean deliveries in 141 hospitals; 1557 discharges recorded at least 1 ARAE (6.6 per 1000; 95% confidence interval [CI], 6.2-6.9). The following factors were associated with a significantly increased risk of ARAEs: Charlson comorbidity index >= 1 (adjusted odds ratio [aOR], 1.2), multiple gestation (aOR, 1.3), postpartum hemorrhage (aOR, 1.5), general anesthesia (aOR, 1.3), hospital annual cesarean delivery volume <200 (aOR, 2.3), and reporting index (aOR, 1.1 per 1 increase per discharge). Fifteen percent of the between-hospital variation in ARAEs was explained by the hospital annual cesarean delivery volume and 6% by the reporting index. Eight hospitals (6%) were classified as good-performing, 104 (74%) as average-performing, and 29 (21%) as bad-performing hospitals. Compared with good-performing hospitals, a 2.3-fold (95% CI, 1.7-3.0) and 5.9-fold (95% CI, 4.5-7.8) increase in the rate of ARAEs was observed in average- and bad performing hospitals, respectively. Bringing up bad-performing hospitals to the level of average-performing hospitals would prevent 466 ARAEs (30%). CONCLUSIONS: Low cesarean delivery volume is the strongest hospital-level predictor of ARAEs in cesarean deliveries and the main determinant of between-hospital variation. Future study to identify other factors and interventions to improve performance in bad-performing hospitals is warranted. PMID- 27195638 TI - The Use of Neuraxial Catheters for Postoperative Analgesia in Neonates: A Multicenter Safety Analysis from the Pediatric Regional Anesthesia Network. AB - BACKGROUND: Currently, there is limited evidence to support the safety of neuraxial catheters in neonates. Safety concerns have been cited as a major barrier to performing large randomized trials in this population. The main objective of this study is to examine the safety of neuraxial catheters in neonates across multiple institutions. Specifically, we sought to determine the incidence of overall and individual complications encountered when neuraxial catheters were used for postoperative analgesia in neonates. METHODS: This was an observational study that used the Pediatric Regional Anesthesia Network database. Complications and adverse events were defined by the presence of at least 1 of the following intraoperative and/or postoperative factors: catheter malfunction (dislodgment/occlusion), infection, block abandoned (unable to place), block failure (no evidence of block), vascular (blood aspiration/hematoma), local anesthetic systemic toxicity, excessive motor block, paresthesia, persistent neurologic deficit, and other (e.g., intra-abdominal misplacement, tremors). Additional analyses were performed to identify the use of potentially toxic doses of local anesthetics. RESULTS: The study cohort included 307 neonates with a neuraxial catheter. There were 41 adverse events and complications recorded, resulting in an overall incidence of complications of 13.3% (95% confidence interval, 9.8%-17.4%). Among the complications, catheter malfunction, catheter contamination, and vascular puncture were common. None of the complications resulted in long-term complications and/or sequelae, resulting in an estimated incidence of any serious complications of 0.3% (95% confidence interval, 0.08% 1.8%). There were 120 of 307 patients who received intraoperative and/or postoperative infusions consistent with a potentially toxic local anesthetic dose in neonates. The incidence of potentially toxic local anesthetic infusion rates increased over time (P = 0.008). CONCLUSIONS: Neuraxial catheter techniques for intraoperative and postoperative analgesia appear to be safe in neonates. Further studies to confirm our results and to establish the efficacy of these techniques across different surgical procedures are required. We suggest that each center that uses neuraxial anesthesia techniques in neonates closely evaluate the dose limits for local anesthetic agents and develop rigorous quality assurance methods to ensure potentially toxic doses are not used. PMID- 27195640 TI - The Effect of "Opt-Out" Regulation on Access to Surgical Care for Urgent Cases in the United States: Evidence from the National Inpatient Sample. AB - BACKGROUND: In 2001, the Center for Medicare and Medicaid Services issued a rule permitting states to "opt-out" of federal regulations requiring physician supervision of nurse anesthetists. We examined the extent to which this rule increased access to anesthesia care for urgent cases. METHODS: Using data from a national sample of inpatient discharges, we examined whether opt-out was associated with an increase in the percentage of patients receiving a therapeutic procedure among patients admitted for appendicitis, bowel obstruction, choledocholithiasis, or hip fracture. We chose these 4 diagnoses because they represent instances where urgent access to a procedure requiring anesthesia is often indicated. In addition, we examined whether opt-out was associated with a reduction in the number of appendicitis patients who presented with a ruptured appendix. In addition to controlling for patient morbidities and demographics, our analysis incorporated a difference-in-differences approach, with additional controls for state-year trends, to reduce confounding. RESULTS: Across all 4 diagnoses, opt-out was not associated with a statistically significant change in the percentage of patients who received a procedure (0.0315 percentage point increase, 95% confidence interval [CI] -0.843 to 0.906 percentage point increase). When broken down by diagnosis, opt-out was also not associated with statistically significant changes in the percentage of patients who received a procedure for bowel obstruction (0.511 percentage point decrease, 95% CI -2.28 to 1.26), choledocholithiasis (2.78 percentage point decrease, 95% CI -6.12 to 0.565), and hip fracture (0.291 percentage point increase, 95% CI -1.76 to 2.94). Opt-out was associated with a small but statistically significant increase in the percentage of appendicitis patients receiving an appendectomy (0.876 percentage point increase, 95% CI 0.194 to 1.56); however, there was no significant change in the percentage of patients presenting with a ruptured appendix (-0.914 percentage point decrease, 95% CI -2.41 to 0.582). Subanalyses showed that the effects of opt-out did not differ in rural versus urban areas. CONCLUSIONS: Based on 2 measures of access, opt-out does not appear to have significantly increased access to anesthesia for urgent inpatient conditions. PMID- 27195641 TI - Clinical Performance Scores Are Independently Associated with the American Board of Anesthesiology Certification Examination Scores. AB - BACKGROUND: It is unknown whether clinical performance during residency is related to the American Board of Anesthesiology (ABA) oral examination scores. We hypothesized that resident clinical performance would be independently associated with oral examination performance because the oral examination is designed to test for clinical judgment. METHOD: We determined clinical performance scores (Zrel) during the final year of residency for all 124 Massachusetts General Hospital (MGH) anesthesia residents who graduated from 2009 to 2013. One hundred eleven graduates subsequently took the ABA written and oral examinations. We standardized each graduate's written examination score (ZPart 1) and oral examination score (ZPart 2) to the national average. Multiple linear regression analysis was used to determine the partial effects of MGH clinical performance scores and ABA written examination scores on ABA oral examination scores. RESULTS: MGH clinical performance scores (Zrel) correlated with both ABA written examination scores (ZPart 1) (r = 0.27; P = 0.0047) and with ABA oral examination scores (ZPart 2) (r = 0.33; P = 0.0005). ABA written examination scores (ZPart 1) correlated with oral examination scores (ZPart 2) (r = 0.46; P = 0.0001). Clinical performance scores (Zrel) and ABA written examination scores (ZPart 1) independently accounted for 4.5% (95% confidence interval [CI], 0.5%-12.4%; P = 0.012) and 20.8% (95% CI, 8.0%-37.2%; P < 0.0001), respectively, of the variance in ABA oral examination scores (ZPart 2). CONCLUSIONS: Clinical performance scores and ABA written examination scores independently accounted for variance in ABA oral examination scores. Clinical performance scores are independently associated with the ABA oral examination scores. PMID- 27195642 TI - Written Comments Made by Anesthesia Residents When Providing Below Average Scores for the Supervision Provided by the Faculty Anesthesiologist. AB - BACKGROUND: Anesthesia residents in our department evaluate the supervision provided by the faculty anesthesiologist with whom they worked the previous day. What advice managers can best provide to the faculty who receive below-average supervision scores is unknown. METHODS: The residents provided numerical answers (1 "never," 2 "rarely," 3 "frequently," or 4 "always") to each of the 9 supervision questions, resulting in a total supervision score. A written comment could also be provided. RESULTS: Over 2.5 years, the response rate to requests for evaluation was 99.1%. There were 13,664 evaluations of 76 faculty including 1387 comments. There were 25 evaluations with a comment of disrespectful behavior. For all 25, the question evaluating whether "the faculty treated me respectfully" was answered <4 (i.e., not "always"). The supervision scores were less than for the other evaluations with comments (P < 0.0001). Each increase in the faculty's number of comments of being disrespectful was associated with a lesser mean score (P = 0.0002). A low supervision score (<3.00; i.e., less than "frequent") had an odds ratio of 85 for disrespectful faculty behavior (P < 0.0001). The predictive value of the supervision score not being low for absence of a comment of disrespectful behavior was 99%. That finding was especially useful because 94% of scores below average (<3.80) were not low (>=3.00). There were 6 evaluations with a comment of insufficient faculty presence. Those evaluations had lesser scores than the other evaluations with comments (P < 0.0001). The 6 faculty with 1 such comment had lesser mean scores than the other faculty (P = 0.0071). There were 34 evaluations with a comment about poor-quality teaching. The evaluations related to poor teaching had lesser scores than the other evaluations with comments (P < 0.0001). The faculty who each received such a comment had lesser mean scores than the other faculty (P < 0.0001). Each increase in the faculty's number of comments of poor-quality teaching was associated with a lesser mean score (P = 0.0002). The 9 supervision questions were internally consistent (Cronbach alpha = 0.948). A faculty with a comment about poor-quality teaching had significant odds of also having a comment about insufficient presence (P = 0.0044). A comment with negative sentiment had significant odds of being about poor-quality teaching rather than being about insufficient presence (odds ratio, 6.00; P < 0.0001). CONCLUSIONS: A faculty who has insufficient presence cannot be providing good teaching. Furthermore, there was negligible correlation between supervision scores and faculty clinical assignments. Thus, insufficient faculty presence accounted for a small proportion of below-average supervision scores and low-quality supervision. Furthermore, scores >=3 have a predictive value for the absence of disrespectful behavior ?99%. Approximately 94% of the faculty supervision scores that were below average were still >=3. Consequently, for the vast majority of the faculty-resident-days, quality of teaching distinguished between below- versus above-average supervision scores. This result is consistent with our prior finding of a strong correlation between 6-month supervision scores and assessments of teaching effectiveness. Taken together, when individual faculty anesthesiologists are counseled about their clinical supervision scores, the attribute to emphasize is quality of clinical teaching. PMID- 27195639 TI - The Anesthesiologist's Role in Treating Abusive Head Trauma. AB - Abusive head trauma (AHT) is the most common cause of severe traumatic brain injury (TBI) in infants and the leading cause of child abuse-related deaths. For reasons that remain unclear, mortality rates after moderate AHT rival those of severe nonintentional TBI. The vulnerability of the developing brain to injury may be partially responsible for the poor outcomes observed after AHT. AHT is mechanistically more complex than nonintentional TBI. The acute-on-chronic nature of the trauma along with synergistic injury mechanisms that include rapid rotation of the brain, diffuse axonal injury, blunt force trauma, and hypoxia ischemia make AHT challenging to treat. The anesthesiologist must understand the complex injury mechanisms inherent to AHT, as well as the pediatric TBI treatment guidelines, to decrease the risk of persistent neurologic disability and death. In this review, we discuss the epidemiology of AHT, differences between AHT and nonintentional TBI, the severe pediatric TBI treatment guidelines in the context of AHT, anesthetic considerations, and ethical and legal reporting requirements. PMID- 27195643 TI - Chronic Pain Without Clear Etiology in Low- and Middle-Income Countries: A Narrative Review. AB - Globally, 8 of the top 12 disabling conditions are related either to chronic pain or to the psychological conditions strongly associated with persistent pain. In this narrative review, we explore the demographic and psychosocial associations with chronic pain exclusively from low- and middle-income countries (LMICs) and compare them with current global data. One hundred nineteen publications in 28 LMICs were identified for review; associations with depression, anxiety, posttraumatic stress, insomnia, disability, gender, age, rural/urban location, education level, income, and additional sites of pain were analyzed for each type of chronic pain without clear etiology. Of the 119 publications reviewed, pain was described in association with disability in 50 publications, female gender in 40 publications, older age in 34 publications, depression in 36 publications, anxiety in 19 publications, and multiple somatic complaints in 13 publications. Women, elderly patients, and workers, especially in low-income and low-education subgroups, were more likely to have pain in multiple sites, mood disorders, and disabilities. In high-income countries, multisite pain without etiology, female gender, and association with mood disturbance and disability may be suggestive of a central sensitization syndrome (CSS). Because each type of prevalent chronic pain without known etiology reviewed had similar associations in LMICs, strategies for assessment and treatment of chronic pain worldwide should consider the possibility of prevalent CSS. Recognition is especially critical in resource poor areas, because treatment of CSS is vastly different than localized chronic pain. PMID- 27195644 TI - Back Pain and Neuraxial Anesthesia. AB - The incidence of back pain after neuraxial anesthesia in the adult population is not different from that after general anesthesia. The pain is usually mild, localized in the low back, rarely radiates to the lower extremities, and has a duration of only a few days. The risk factors for development of back pain include the lithotomy position, multiple attempts at block placement, duration of surgery longer than 2.5 hours, body mass index >=32 kg/m, and a history of back pain. However, there is no permanent worsening of preexisting back pain after neuraxial anesthesia. The back pain has been attributed to tears in the ligaments, fascia, or bone with localized bleeding; immobility of the spine; relaxation of the paraspinal muscles under anesthesia; flattening of the normal lumbar convexity; and stretching and straining of the lumbosacral ligaments and joint capsules. The addition of an anti-inflammatory drug to the local anesthetic used for skin infiltration may decrease the incidence and severity of back pain. The use of spinal or epidural anesthesia in the adult, non-obstetric and obstetric populations should depend on the advantages offered by the technique and not on the occurrence of back pain after the procedure. Additional studies are needed to confirm the efficacy of epidural dexamethasone, or other steroids, or the addition of an anti-inflammatory drug to the local anesthetic infiltration for the prevention of back pain after neuraxial anesthesia. Future studies should involve a physician with expertise in the evaluation of chronic low back pain to help identify the cause of the back pain and institute appropriate treatment(s). PMID- 27195645 TI - Perioperative Safety: Learning, Not Taking, from Aviation. PMID- 27195646 TI - Opioids After Discharge in Pediatric Patients. PMID- 27195647 TI - In Response. PMID- 27195648 TI - Regarding "Quality Improvement Demands Quality Data". PMID- 27195649 TI - Observations and Suggestions for Millennial Resident Applicant Interviewees. PMID- 27195650 TI - Caroline Palmer and the History of Operating Room Management. PMID- 27195652 TI - Inhibition of TNF-alpha-mediated NF-kappaB Activation by Ginsenoside Rg1 Contributes the Attenuation of Cardiac Hypertrophy Induced by Abdominal Aorta Coarctation. AB - Ginsenoside Rg1 (Rg1), a protopanaxadiol saponin extracted from Chinese medicine Panax ginseng C.A. Meyer, has been demonstrated to inhibit the cardiac hypertrophy. However, the molecular mechanisms underlying the inhibition remain poorly understood. Activation of nuclear factor-kappa B (NF-kappaB) mediated by tumor necrosis factor alpha (TNF-alpha) gets involved in the cardiac hypertrophy. This study is designed to investigate the effects and the potential mechanism of Rg1 on the abdominal aorta coarctation (AAC)-induced cardiac hypertrophy with focus on TNF-alpha/NF-kappaB signaling pathway. The results showed that oral administration of Rg1 dose-dependently improved the pathological changes, decreased the ratios of left ventricular weight/body weight (LVW/BW) and heart weight/BW (HW/BW), corrected the dysfunction of the cardiac hemodynamics by decreasing the left ventricular systolic pressure and left ventricular end diastolic pressure and increasing the maximal rate of left ventricular systolic and diastolic pressure (+/-dp/dtmax) compared with the AAC alone. Rg1 also downregulated the atrial natriuretic peptide mRNA expression and decreased the mRNA and protein expression of TNF-alpha in the heart tissue of rats compared with the AAC alone. In addition, Rg1 and BAY, the specific inhibitor of NF kappaB, decreased the protein content and downregulated the mRNA expression of atrial natriuretic peptide in neonatal rat ventricular myocytes treated with TNF alpha. Furthermore, Rg1 increased the protein expression of p65, the subunit of NF-kappaB, in cytoplasm and decreased the expression p65 in nucleus of the heart tissue of rats undergoing the AAC and of neonatal rat ventricular myocytes treated with TNF-alpha. The results suggested that Rg1 attenuates the AAC-induced cardiac hypertrophy through inhibition of TNF-alpha/NF-kappaB signaling pathway. PMID- 27195653 TI - CMX-2043 Mechanisms of Action In Vitro. AB - alpha-Lipoic acid has been shown to provide cytoprotection in some tissues through antioxidant and antiapoptotic mechanisms. We have enhanced these properties by synthetic modification, resulting in a new chemical entity, CMX 2043, with proven efficacy in an animal model of cardiac ischemia-reperfusion injury. The present studies compare cytoprotective cellular pathways of R-alpha lipoic acid and CMX-2043. Biochemical and cellular assays were used to compare antioxidant potency, tyrosine kinase activation, and protein kinase B (Akt) phosphorylation. CMX-2043 was more effective than lipoic acid in antioxidant effect, activation of insulin receptor kinase, soluble tyrosine kinase, and Akt phosphorylation. Activation of insulin-like growth factor 1 receptor was similar for both. CMX-2043 stimulation of Akt phosphorylation was abolished by the phosphatidylinositide 3-kinase inhibitor LY294002. Consistent with Akt activation, CMX-2043 reduced carbachol-induced calcium overload. The S stereoisomer of CMX-2043 was less active in the biochemical assays than the R isomer. These results are consistent with cytoprotection through activation of Akt and antioxidant action. CMX-2043 may thus provide a pharmacological approach to cytoprotection consistent with established anti-apoptotic mechanisms. PMID- 27195655 TI - Correlation of Deoxynivalenol Accumulation in Fusarium-Infected Winter and Spring Wheat Cultivars with Secondary Metabolites at Different Growth Stages. AB - Fusarium infection in wheat causes Fusarium head blight, resulting in yield losses and contamination of grains with trichothecenes. Some plant secondary metabolites inhibit accumulation of trichothecenes. Eighteen Fusarium infected wheat cultivars were harvested at five time points and analyzed for the trichothecene deoxynivalenol (DON) and 38 wheat secondary metabolites (benzoxazinoids, phenolic acids, carotenoids, and flavonoids). Multivariate analysis showed that harvest time strongly impacted the content of secondary metabolites, more distinctly for winter wheat than spring wheat. The benzoxazinoid 2-beta-glucopyranoside-2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA-glc), alpha-tocopherol, and the flavonoids homoorientin and orientin were identified as potential inhibitors of DON accumulation. Several phenolic acids, lutein and beta-carotene also affected DON accumulation, but the effect varied for the two wheat types. The results could form a basis for choosing wheat cultivars using metabolite profiling as a marker for selecting wheat cultivars with improved resistance against Fusarium head blight and accumulation of trichothecene toxins in wheat heads. PMID- 27195654 TI - Inverse Temperature Dependence of Nuclear Quantum Effects in DNA Base Pairs. AB - Despite the inherently quantum mechanical nature of hydrogen bonding, it is unclear how nuclear quantum effects (NQEs) alter the strengths of hydrogen bonds. With this in mind, we use ab initio path integral molecular dynamics to determine the absolute contribution of NQEs to the binding in DNA base pair complexes, arguably the most important hydrogen-bonded systems of all. We find that depending on the temperature, NQEs can either strengthen or weaken the binding within the hydrogen-bonded complexes. As a somewhat counterintuitive consequence, NQEs can have a smaller impact on hydrogen bond strengths at cryogenic temperatures than at room temperature. We rationalize this in terms of a competition of NQEs between low-frequency and high-frequency vibrational modes. Extending this idea, we also propose a simple model to predict the temperature dependence of NQEs on hydrogen bond strengths in general. PMID- 27195656 TI - Effect of antihypertensive treatment with lercanidipine on endothelial progenitor cells and inflammation in patients with mild to moderate essential hypertension. AB - BACKGROUND: It has been demonstrated that circulating endothelial progenitor cells (EPCs) number reflects the endogenous vascular repair ability, with the EPCs pool declining in presence of cardiovascular risk factors. Several drugs, including dihydropyridine calcium channel blockers, have been reported to elicit antioxidant and anti-inflammatory properties, as well as to improve vascular remodeling and dysfunction. However, no data are available about the effects of lercanidipine on EPCs. The aim of the present study was therefore to investigate the effects of short-term treatment with lercanidipine on circulating EPCs, as well as on indices of inflammation and oxidative stress. PATIENTS AND METHODS: Twenty essential hypertensive patients were included in the study and treated for 4 weeks with lercanidipine 20 mg per day orally. Investigations were performed in basal condition, after appropriate wash out of previous treatments, and after 4 weeks of lercanidipine treatment. Inflammatory and oxidative stress markers were assessed by ELISA technique. Lin-/7AAD-/CD34+/CD133+/VEGFR-2 + and Lin-/7AAD /CD34+/VEGFR-2 + cells were identified by flow cytometry and considered as EPCs. EPCs cells were expressed as number of cells per million Lin-mononuclear cells. RESULTS: Circulating EPCs were significantly increased after lercanidipine treatment (CD34+/CD133+/VEGFR-2 + cells: 78.3 +/- 64.5 vs 46.6 +/- 32.8; CD34+/VEGFR-2+: 87996 +/- 165116 vs 1026 +/- 1559, respectively, p < 0.05). A modest reduction in circulating indices of inflammation was also observed. CONCLUSIONS: In conclusion, lercanidipine is able to increase the number of circulating EPCs, possibly through a reduction of low-grade inflammation. PMID- 27195657 TI - Amphipathicity Determines Different Cytotoxic Mechanisms of Lysine- or Arginine Rich Cationic Hydrophobic Peptides in Cancer Cells. AB - Cationic amphipathic peptides (CAPs) are known to be able to cause membrane destabilization and induce cell death, yet how the hydrophobicity, amphipathicity, and lysine (K)/arginine (R) composition synergistically affect the peptide activity remains incompletely understood. Here, we designed a panel of peptides based on the well-known anticancer peptide KLA. Increasing hydrophobicity enhanced the cytotoxicities of both the K- and R-rich peptides. Peptides with an intact amphipathic helical interface can cause instant cell death through a membrane lysis mechanism. Interestingly, rearranging the residue positions to minimize amphipathicity caused a great decrease of cytotoxicity to the K-rich peptides but not to the R-rich peptides. The amphipathicity-minimized R-rich peptide 6 (RL2) (RLLRLLRLRRLLRL-NH2) penetrated the cell membrane and induced caspase-3-dependent apoptotic cell death. We found that the modulation of hydrophobicity, amphipathicity, and K/R residues leads to distinct mechanisms of action of cationic hydrophobic peptides. Amphipathicity-reduced, arginine-rich cationic hydrophobic peptides (CHPs) may represent a new class of peptide therapeutics. PMID- 27195658 TI - An Overview of the 2009 A(H1N1) Pandemic in Europe: Efficiency of the Vaccination and Healthcare Strategies. AB - 2009 A(H1N1) data for 13 European countries obtained from the weekly influenza surveillance overview (WISO) reports of European Centre for Disease Prevention and Control (ECDC) in the form of weekly cumulative fatalities are analyzed. The variability of relative fatalities is explained by the health index of analyzed countries. Vaccination and healthcare practices as reported in the literature are used to explain the departures from this model. The timing of the vaccination with respect to the peak of the epidemic and its role in the efficiency of the vaccination is discussed. Simulations are used to show that on-time vaccination reduces considerably the final value of R( t), R f , but it has little effect on the shape of normalized curve R( t)/ R f . PMID- 27195659 TI - Emerging antibodies for the treatment of multiple myeloma. AB - INTRODUCTION: Monoclonal antibodies mark the beginning of a new era in the context of multiple myeloma (MM) treatment. Numerous antibodies have been tested or are currently in development for patients with MM, in order to improve tolerability and quality of life. AREAS COVERED: This manuscript reviews emerging antibodies for the treatment of MM i.e. elotuzumab, daratumumab, MOR03087, isatuximab, bevacizumab, cetuximab, siltuximab, tocilizumab, elsilimomab, azintrel, rituximab, tositumomab, milatuzumab, lucatumumab, dacetuzumab, figitumumab, dalotuzumab, AVE1642, tabalumab, pembrolizumab, pidilizumab, nivolumab. EXPERT OPINION: Amongst these antibodies, elotuzumab which targets SLAMF-7 and daratumumab which targets CD38, have been recently approved by FDA for patients with relapsed/refractory MM. Both agents are well tolerated. Multiple clinical trials incorporating these monoclonal antibodies in MM treatment are currently ongoing. Of special interest are the anticipated results of phase III clinical trials with elotuzumab [NCT0189164; NCT01335399; NCT02495922] and daratumumab [NCT02252172; NCT02195479] in newly diagnosed MM patients. Moreover, of great interest are the awaited data on pembrolizumabin combination with pomalidomide and dexamethasone in refractory/relapsed MM patients [NCT02576977] and in combination with lenalidomide and dexamethasone in newly diagnosed MM patients. It seems that the incorporation of monoclonal antibodies will change the landscape of myeloma therapy in the near future. PMID- 27195660 TI - Length of Hospital Stay Prediction at the Admission Stage for Cardiology Patients Using Artificial Neural Network. AB - For hospitals' admission management, the ability to predict length of stay (LOS) as early as in the preadmission stage might be helpful to monitor the quality of inpatient care. This study is to develop artificial neural network (ANN) models to predict LOS for inpatients with one of the three primary diagnoses: coronary atherosclerosis (CAS), heart failure (HF), and acute myocardial infarction (AMI) in a cardiovascular unit in a Christian hospital in Taipei, Taiwan. A total of 2,377 cardiology patients discharged between October 1, 2010, and December 31, 2011, were analyzed. Using ANN or linear regression model was able to predict correctly for 88.07% to 89.95% CAS patients at the predischarge stage and for 88.31% to 91.53% at the preadmission stage. For AMI or HF patients, the accuracy ranged from 64.12% to 66.78% at the predischarge stage and 63.69% to 67.47% at the preadmission stage when a tolerance of 2 days was allowed. PMID- 27195661 TI - Mono- and Dinuclear Manganese Carbonyls Supported by 1,8-Disubstituted (L = Py, SMe, SH) Anthracene Ligand Scaffolds. AB - Presented herein is a synthetic scheme to generate symmetric and asymmetric ligands based on a 1,8-disubstituted anthracene scaffold. The metal-binding scaffolds were prepared by aryl chloride activation of 1,8-dichloroanthracene using Suzuki-type couplings facilitated by [Pd(dba)2] as a Pd source; the choice of cocatalyst (XPhos or SPhos) yielded symmetrically or asymmetrically substituted scaffolds (respectively): namely, Anth-SMe2 (3), Anth-N2 (4), and Anth-NSMe (6). The ligands exhibit a nonplanar geometry in the solid state (X ray), owing to steric hindrance between the anthracene scaffold and the coupled aryl units. To determine the flexibility and binding characteristics of the anthracene-based ligands, the symmetric scaffolds were complexed with [Mn(CO)5Br] to afford the mononuclear species [(Anth-SMe2)Mn(CO)3Br] (8) and [(Anth N2)Mn(CO)3Br] (9), in which the donor moieties chelate the Mn center in a cis fashion. The asymmetric ligand Anth-NSMe (6) binds preferentially through the py moieties, affording the bis-ligated complex [(Anth-NSMe)2Mn(CO)3Br] (10), wherein the thioether-S donors remain unbound. Alternatively, deprotection of the thioether in 6 affords the free thiol ligand Anth-NSH (7), which more readily binds the Mn center. Complexation of 7 ultimately affords the mixed-valence Mn(I)/Mn(II) dimer of formula [(Anth-NS)3Mn2(CO)3] (11), which exhibits a fac {Mn(CO)3} unit supported by a triad of bridging thiolates, which are in turn ligated to a supporting Mn(II) center (EPR: |D| = 0.053 cm(-1), E/|D| = 0.3, Aiso = -150 MHz). All of the metal complexes have been characterized by single-crystal X-ray diffraction, IR spectroscopy and NMR/EPR measurements-all of which demonstrate that the meta-linked, anthracene-based ligand scaffold is a viable approach for the coordination of metal carbonyls. PMID- 27195662 TI - Overview of the clinical trials on bioresorbable vascular scaffold. AB - Although several new scaffolds are progressively being investigated and entering the clinical scene, BRS has accumulated the largest experience by far including detailed evaluation of the first patients studied followed almost in parallel by clinical evaluation and worldwide randomized evaluation for non-inferiority against best contemporary metallic DES. Available evidence shows that careful procedural technique is required for proper and safe delivery of the current generation scaffolds. Future studies will indicate whether all or only selected patient or lesion subsets will ultimately benefit from treatment with fully bioresorbable devices. PMID- 27195663 TI - Imaging and functional assessment of bioresorbable scaffolds. AB - Bioresorbable vascular scaffolds (BRS) are novel devices designed to provide transient vessel support to drug-delivery capability without the potential long term limitations of metallic drug-eluting stents. The technology, heralded as the latest revolution in the field of percutaneous coronary intervention, could overcome many of the long-term safety concerns associated with metallic stents and possibly even convey a further clinical benefit. However, despite its theoretical advantages, the safety and efficacy of the first generation BRS remain unclear in all-comer patient populations. Invasive imaging modalities and methodologies were developed to guide BRS implantation and monitor the interaction between the scaffold and the vessel at long-term follow-up. These tools are helpful to avoid some of the pitfalls associated with BRS implantation and may improve the clinical outcome of these devices. The present review aims to report the most recent data regarding multi-imaging modalities as guidance and follow-up of coronary interventions involving the use of BRS. PMID- 27195664 TI - Construction and Validation of a Perceived Physical Literacy Instrument for Physical Education Teachers. AB - The purpose of this study was to construct and validate a "Perceived Physical Literacy Instrument" (PPLI) for physical education teachers. Based on literature review and focus group interviews, an 18-item instrument was developed for the initial tests. This self-report measure, using a 5-point Likert scale, formed the PPLI and was administered to 336 physical education teachers in Hong Kong. The sample was randomly split, and exploratory and confirmatory factor analyses resulted in a 9-item, 3-factor scale. Exploratory factor analysis (EFA) item loadings ranged from 0.69 to 0.87, and Cronbach's alpha ranged from 0.73 to 0.76. Confirmatory factor analysis (CFA) showed that the construct demonstrated good fit to the model. The PPLI thus appeared to be reliable and valid to measure the perceived physical literacy of physical education teachers. It is argued that the instrument can be used for both research and applied purposes and potential uses for the instrument in physical education, medical and health settings are discussed. PMID- 27195666 TI - Two Different Maintenance Strategies in the Hospital Environment: Preventive Maintenance for Older Technology Devices and Predictive Maintenance for Newer High-Tech Devices. AB - A maintenance program generated through the consideration of characteristics and failures of medical equipment is an important component of technology management. However, older technology devices and newer high-tech devices cannot be efficiently managed using the same strategies because of their different characteristics. This study aimed to generate a maintenance program comprising two different strategies to increase the efficiency of device management: preventive maintenance for older technology devices and predictive maintenance for newer high-tech devices. For preventive maintenance development, 589 older technology devices were subjected to performance verification and safety testing (PVST). For predictive maintenance development, the manufacturers' recommendations were used for 134 high-tech devices. These strategies were evaluated in terms of device reliability. This study recommends the use of two different maintenance strategies for old and new devices at hospitals in developing countries. Thus, older technology devices that applied only corrective maintenance will be included in maintenance like high-tech devices. PMID- 27195665 TI - Ubiquitylation of Rad51d Mediated by E3 Ligase Rnf138 Promotes the Homologous Recombination Repair Pathway. AB - Ubiquitylation has an important role as a signal transducer that regulates protein function, subcellular localization, or stability during the DNA damage response. In this study, we show that Ring domain E3 ubiquitin ligases RNF138 is recruited to DNA damage site quickly. And the recruitment is mediated through its Zinc finger domains. We further confirm that RNF138 is phosphorylated by ATM at Ser124. However, the phosphorylation was dispensable for recruitment to the DNA damage site. Our findings also indicate that RAD51 assembly at DSB sites following irradiation is dramatically affected in RNF138-deficient cells. Hence, RNF138 is likely involved in regulating homologous recombination repair pathway. Consistently, efficiency of homologous recombination decreased observably in RNF138-depleted cells. In addition, RNF138-deficient cell is hypersensitive to DNA damage insults, such as IR and MMS. And the comet assay confirmed that RNF138 directly participated in DNA damage repair. Moreover, we find that RAD51D directly interacted with RNF138. And the recruitment of RAD51D to DNA damage site is delayed and unstable in RNF138-depleted cells. Taken together, these results suggest that RNF138 promotes the homologous recombination repair pathway. PMID- 27195667 TI - A Simple yet Accurate Method for the Estimation of the Biovolume of Planktonic Microorganisms. AB - Determining the biomass of microbial plankton is central to the study of fluxes of energy and materials in aquatic ecosystems. This is typically accomplished by applying proper volume-to-carbon conversion factors to group-specific abundances and biovolumes. A critical step in this approach is the accurate estimation of biovolume from two-dimensional (2D) data such as those available through conventional microscopy techniques or flow-through imaging systems. This paper describes a simple yet accurate method for the assessment of the biovolume of planktonic microorganisms, which works with any image analysis system allowing for the measurement of linear distances and the estimation of the cross sectional area of an object from a 2D digital image. The proposed method is based on Archimedes' principle about the relationship between the volume of a sphere and that of a cylinder in which the sphere is inscribed, plus a coefficient of 'unellipticity' introduced here. Validation and careful evaluation of the method are provided using a variety of approaches. The new method proved to be highly precise with all convex shapes characterised by approximate rotational symmetry, and combining it with an existing method specific for highly concave or branched shapes allows covering the great majority of cases with good reliability. Thanks to its accuracy, consistency, and low resources demand, the new method can conveniently be used in substitution of any extant method designed for convex shapes, and can readily be coupled with automated cell imaging technologies, including state-of-the-art flow-through imaging devices. PMID- 27195668 TI - What drivers phenotypic divergence in Leymus chinensis (Poaceae) on large-scale gradient, climate or genetic differentiation? AB - Elucidating the driving factors among-population divergence is an important task in evolutionary biology, however the relative contribution from natural selection and neutral genetic differentiation has been less debated. A manipulation experiment was conducted to examine whether the phenotypic divergence of Leymus chinensis depended on climate variations or genetic differentiations at 18 wild sites along a longitudinal gradient from 114 to 124 degrees E in northeast China and at common garden condition of transplantation. Demographical, morphological and physiological phenotypes of 18 L. chinensis populations exhibited significant divergence along the gradient, but these divergent variations narrowed significantly at the transplantation. Moreover, most of the phenotypes were significantly correlated with mean annual precipitation and temperature in wild sites, suggesting that climatic variables played vital roles in phenotypic divergence of the species. Relative greater heterozygosity (HE), genotype evenness (E) and Shannon-Wiener diversity (I) in western group of populations suggested that genetic differentiation also drove phenotypic divergence of the species. However, neutral genetic differentiation (FST = 0.041) was greatly lower than quantitative differentiation (QST = 0.199), indicating that divergent selection/climate variable was the main factor in determining the phenotypic divergence of the species along the large-scale gradient. PMID- 27195670 TI - Update to Rociletinib Data with the RECIST Confirmed Response Rate. PMID- 27195669 TI - Developing a Gene Biomarker at the Tipping Point of Adaptive and Adverse Responses in Human Bronchial Epithelial Cells. AB - Determining mechanism-based biomarkers that distinguish adaptive and adverse cellular processes is critical to understanding the health effects of environmental exposures. Shifting from in vivo, low-throughput toxicity studies to high-throughput screening (HTS) paradigms and risk assessment based on in vitro and in silico testing requires utilizing toxicity pathway information to distinguish adverse outcomes from recoverable adaptive events. Little work has focused on oxidative stresses in human airway for the purposes of predicting adverse responses. We hypothesize that early gene expression-mediated molecular changes could be used to delineate adaptive and adverse responses to environmentally-based perturbations. Here, we examined cellular responses of the tracheobronchial airway to zinc (Zn) exposure, a model oxidant. Airway derived BEAS-2B cells exposed to 2-10 MUM Zn2+ elicited concentration- and time-dependent cytotoxicity. Normal, adaptive, and cytotoxic Zn2+ exposure conditions were determined with traditional apical endpoints, and differences in global gene expression around the tipping point of the responses were used to delineate underlying molecular mechanisms. Bioinformatic analyses of differentially expressed genes indicate early enrichment of stress signaling pathways, including those mediated by the transcription factors p53 and NRF2. After 4 h, 154 genes were differentially expressed (p < 0.01) between the adaptive and cytotoxic Zn2+ concentrations. Nearly 40% of the biomarker genes were related to the p53 signaling pathway with 30 genes identified as likely direct targets using a database of p53 ChIP-seq studies. Despite similar p53 activation profiles, these data revealed widespread dampening of p53 and NRF2-related genes as early as 4 h after exposure at higher, unrecoverable Zn2+ exposures. Thus, in our model early increased activation of stress response pathways indicated a recoverable adaptive event. Overall, this study highlights the importance of characterizing molecular mechanisms around the tipping point of adverse responses to better inform HTS paradigms. PMID- 27195671 TI - Study of a DNA Duplex by Nuclear Magnetic Resonance and Molecular Dynamics Simulations. Validation of Pulsed Dipolar Electron Paramagnetic Resonance Distance Measurements Using Triarylmethyl-Based Spin Labels. AB - Pulse dipole-dipole electron paramagnetic resonance (EPR) spectroscopy (double electron-electron resonance [DEER] or pulse electron-electron double resonance [PELDOR] and double quantum coherence [DQC]) allows for measurement of distances in biomolecules and can be used at low temperatures in a frozen solution. Recently, the possibility of distance measurement in a nucleic acid at a physiological temperature using pulse EPR was demonstrated. In these experiments, triarylmethyl (TAM) radicals with long memory time of the electron spin served as a spin label. In addition, the duplex was immobilized on modified silica gel particles (Nucleosil DMA); this approach enables measurement of interspin distances close to 4.5 nm. Nevertheless, the possible influence of TAM on the structure of a biopolymer under study and validity of the data obtained by DQC are debated. In this paper, a combination of molecular dynamics (MD) and nuclear magnetic resonance (NMR) methods was used for verification of interspin distances measured by the X-band DQC method. NMR is widely used for structural analysis of biomolecules under natural conditions (room temperature and an aqueous solution). The ultraviolet (UV) melting method and thermal series (1)H NMR in the range 5-95 degrees C revealed the presence of only the DNA duplex in solution at oligonucleotide concentrations 1 MUM to 1.1 mM at temperatures below 40 degrees C. The duplex structures and conformation flexibility of native and TAM-labeled DNA complexes obtained by MD simulation were the same as the structure obtained by NMR refinement. Thus, we showed that distance measurements at physiological temperatures by the X-band DQC method allow researchers to obtain valid structural information on an unperturbed DNA duplex using terminal TAM spin labels. PMID- 27195672 TI - Upregulated long non-coding RNA AGAP2-AS1 represses LATS2 and KLF2 expression through interacting with EZH2 and LSD1 in non-small-cell lung cancer cells. AB - Recently, long non-coding RNAs (lncRNAs) are identified as new crucial regulators of diverse cellular processes, including cell proliferation, differentiation and cancer cells metastasis. Accumulating evidence has revealed that aberrant lncRNA expression plays important roles in carcinogenesis and tumor progression. However, the expression pattern and biological function of lncRNAs in non-small cell lung cancer (NSCLC) remain largely unknown. In this study, we performed comprehensive analysis of lncRNA expression in human NSCLC samples by using microarray data from Gene Expression Omnibus. After validation in a cohort of 80 pairs of NSCLC tissues, we identified a differentially expressed novel oncogenic lncRNA termed as AGAP2-AS1. The AGAP2-AS1 expression level was significantly upregulated in NSCLC tissues and negatively correlated with poor prognostic outcomes in patients. In vitro loss- and gain-of-function assays revealed that AGAP2-AS1 knockdown inhibited cell proliferation, migration and invasion, and induced cell apoptosis. In vivo assays also confirmed the ability of AGAP2-AS1 to promote tumor growth. Furthermore, mechanistic investigation showed that AGAP2 AS1 could bind with enhancer of zeste homolog 2 and lysine (K)-specific demethylase 1A, and recruit them to KLF2 and LATS2 promoter regions to repress their transcription. Taken together, our findings indicate that AGAP2-AS1 may act as an oncogene by repressing tumor-suppressor LATS2 and KLF2 transcription. By clarifying the AGAP2-AS1 mechanisms underlying NSCLC development and progression, these findings might promote the development of novel therapeutic strategies for this disease. PMID- 27195674 TI - Allele-specific silencing of EEC p63 mutant R304W restores p63 transcriptional activity. AB - EEC (ectrodactily-ectodermal dysplasia and cleft lip/palate) syndrome is a rare genetic disease, autosomal dominant inherited. It is part of the ectodermal dysplasia disorders caused by heterozygous mutations in TP63 gene. EEC patients present limb malformations, orofacial clefting, skin and skin's appendages defects, ocular abnormalities. The transcription factor p63, encoded by TP63, is a master gene for the commitment of ectodermal-derived tissues, being expressed in the apical ectodermal ridge is critical for vertebrate limb formation and, at a later stage, for skin and skin's appendages development. The DeltaNp63alpha isoform is predominantly expressed in epithelial cells and it is indispensable for preserving the self-renewal capacity of adult stem cells and to engage specific epithelial differentiation programs. Small interfering RNA (siRNA) offers a potential therapy approach for EEC patients by selectively silencing the mutant allele. Here, using a systemic screening based on a dual-luciferase reported gene assay, we have successfully identified specific siRNAs for repressing the EEC-causing p63 mutant, R304W. Upon siRNA treatment, we were able to restore DeltaNp63-WT allele transcriptional function in induced pluripotent stem cells that were derived from EEC patient biopsy. This study demonstrates that siRNAs approach is promising and, may pave the way for curing/delaying major symptoms, such as cornea degeneration and skin erosions in young EEC patients. PMID- 27195673 TI - Fatty acid oxidation and carnitine palmitoyltransferase I: emerging therapeutic targets in cancer. AB - Tumor cells exhibit unique metabolic adaptations that are increasingly viewed as potential targets for novel and specific cancer therapies. Among these targets, the carnitine palmitoyltransferase system is responsible for delivering the long chain fatty acid (FA) from cytoplasm into mitochondria for oxidation, where carnitine palmitoyltransferase I (CPTI) catalyzes the rate-limiting step of fatty acid oxidation (FAO). With increasing understanding of the crucial role had by fatty acid oxidation in cancer, CPTI has received renewed attention as a pivotal mediator in cancer metabolic mechanism. CPTI activates FAO and fuels cancer growth via ATP and NADPH production, constituting an essential part of cancer metabolism adaptation. Moreover, CPTI also functionally intertwines with other key pathways and factors to regulate gene expression and apoptosis of cancer cell. Here, we summarize recent findings and update the current understanding of FAO and CPTI in cancer and provide theoretical basis for this enzyme as an emerging potential molecular target in cancer therapeutic intervention. PMID- 27195675 TI - Knockdown of linc-UFC1 suppresses proliferation and induces apoptosis of colorectal cancer. AB - Long intergenic noncoding RNAs (lincRNAs) have important roles in biological functions, molecular mechanisms and prognostic values in colorectal cancer (CRC). In this context, the roles of linc-UFC1 remain to be elucidated. In this study, linc-UFC1 was overexpressed in CRC patient tissues and positively correlated with tumor grade, N stage and M stage. Inhibition of linc-UFC1 resulted in cell proliferation inhibition and G1 cell cycle arrest, which was mediated by cyclin D1, CDK4, Rb and phosphorylated Rb. In addition, inhibition of linc-UFC1 induced cell apoptosis through the intrinsic apoptosis signaling pathway, as evidenced by the activation of caspase-9 and caspase-3. An investigation of the signaling pathway revealed that the effects on proliferation and apoptosis following linc UFC1 knockdown were mediated by suppression of beta-catenin and activation of phosphorylated P38. Furthermore, the P38 inhibitor SB203580 could attenuate the apoptotic effect achieved by linc-UFC1 knockdown, confirming the involvement of P38 signaling in the induced apoptosis. Taken together, linc-UFC1 might have a critical role in pro-proliferation and anti-apoptosis in CRC by regulating the cell cycle, intrinsic apoptosis, and beta-catenin and P38 signaling. Thus, linc UFC1 could be a potential therapeutic target and novel molecular biomarker for CRC. PMID- 27195676 TI - beta-Arrestin1 inhibits chemotherapy-induced intestinal stem cell apoptosis and mucositis. AB - The mechanism of chemotherapy-induced gastrointestinal (GI) syndrome (CIGIS) is still controversial, and it is unclear whether chemotherapy induces intestinal stem cell (ISC) apoptosis. beta-Arrestins are regulators and mediators of G protein-coupled receptor signaling in cell apoptosis, division and growth. In this study, we aimed to investigate whether chemotherapy induces ISC apoptosis to contribute to mucositis in CIGIS and whether beta-arrestin1 (beta-arr1) is involved in this apoptosis. Different chemotherapeutic agents were used to generate a CIGIS model. Lgr5-EGFP-IRES-creERT2(+/-) knock-in mice were used as a CIGIS model to investigate ISC apoptosis. beta-arr1 knockout mice were used to determine whether beta-arr1 is involved in the apoptosis in CIGIS. Intestinal histology was performed, the ISC apoptosis was analyzed and the mucosal barrier was examined. The effects of beta-arr1 in apoptosis were investigated in the samples from humans and mice as well as in cell lines. Here, we demonstrate that chemotherapy induced intestinal mucositis by promoting crypt cell apoptosis, especially in Lgr5+ stem cells and Paneth cells but not in goblet cells, epithelial cells or vascular endothelial cells. Furthermore, beta-arr1 deficiency exacerbated the Lgr5+ stem cell apoptosis, but not Paneth cell apoptosis, in CIGIS. In addition, the data showed that beta-arr1 reduced the chemotherapy induced Lgr5+ stem cell apoptosis by inhibiting endoplasmic reticulum stress mediated mitochondrial apoptotic signaling. Our study indicates that beta-arr1 inhibits chemotherapy-induced ISC apoptosis to alleviate intestinal mucositis in CIGIS. PMID- 27195677 TI - praja2 regulates KSR1 stability and mitogenic signaling. AB - The kinase suppressor of Ras 1 (KSR1) has a fundamental role in mitogenic signaling by scaffolding components of the Ras/MAP kinase pathway. In response to Ras activation, KSR1 assembles a tripartite kinase complex that optimally transfers signals generated at the cell membrane to activate ERK. We describe a novel mechanism of ERK attenuation based on ubiquitin-dependent proteolysis of KSR1. Stimulation of membrane receptors by hormones or growth factors induced KSR1 polyubiquitination, which paralleled a decline of ERK1/2 signaling. We identified praja2 as the E3 ligase that ubiquitylates KSR1. We showed that praja2 dependent regulation of KSR1 is involved in the growth of cancer cells and in the maintenance of undifferentiated pluripotent state in mouse embryonic stem cells. The dynamic interplay between the ubiquitin system and the kinase scaffold of the Ras pathway shapes the activation profile of the mitogenic cascade. By controlling KSR1 levels, praja2 directly affects compartmentalized ERK activities, impacting on physiological events required for cell proliferation and maintenance of embryonic stem cell pluripotency. PMID- 27195678 TI - Apoptotic CD8 T-lymphocytes disable macrophage-mediated immunity to Trypanosoma cruzi infection. AB - Chagas disease is caused by infection with the protozoan Trypanosoma cruzi. CD8 T lymphocytes help to control infection, but apoptosis of CD8 T cells disrupts immunity and efferocytosis can enhance parasite infection within macrophages. Here, we investigate how apoptosis of activated CD8 T cells affects M1 and M2 macrophage phenotypes. First, we found that CD8 T-lymphocytes and inflammatory monocytes/macrophages infiltrate peritoneum during acute T. cruzi infection. We show that treatment with anti-Fas ligand (FasL) prevents lymphocyte apoptosis, upregulates type-1 responses to parasite antigens, and reduces infection in macrophages cocultured with activated CD8 T cells. Anti-FasL skews mixed M1/M2 macrophage profiles into polarized M1 phenotype, both in vitro and following injection in infected mice. Moreover, inhibition of T-cell apoptosis induces a broad reprogramming of cytokine responses and improves macrophage-mediated immunity to T. cruzi. The results indicate that disposal of apoptotic CD8 T cells increases M2-macrophage differentiation and contributes to parasite persistence. PMID- 27195680 TI - SEASON OF DELTAMETHRIN APPLICATION AFFECTS FLEA AND PLAGUE CONTROL IN WHITE TAILED PRAIRIE DOG (CYNOMYS LEUCURUS) COLONIES, COLORADO, USA. AB - In 2008 and 2009, we evaluated the duration of prophylactic deltamethrin treatments in white-tailed prairie dog ( Cynomys leucurus ) colonies and compared effects of autumn or spring dust application in suppressing flea numbers and plague. Plague occurred before and during our experiment. Overall, flea abundance tended to increase from May or June to September, but it was affected by deltamethrin treatment and plague dynamics. Success in trapping prairie dogs (animals caught/trap days) declined between June and September at all study sites. However, by September trap success on dusted sites (19%; 95% confidence interval [CI] 16-22%) was about 15-fold greater than on undusted control sites (1%; CI 0.3-4%; P<=0.0001). Applying deltamethrin dust as early as 12 mo prior seemed to afford some protection to prairie dogs. Our data showed that dusting even a portion of a prairie dog colony can prolong its persistence despite epizootic plague. Autumn dusting may offer advantages over spring in suppressing overwinter or early-spring flea activity, but timing should be adjusted to precede the annual decline in aboveground activity for hibernating prairie dog species. Large colony complexes or collections of occupied but fragmented habitat may benefit from dusting some sites in spring and others in autumn to maximize flea suppression in a portion of the complex or habitat year-round. PMID- 27195681 TI - CITIZEN SCIENTISTS MONITOR A DEADLY FUNGUS THREATENING AMPHIBIAN COMMUNITIES IN NORTHERN COASTAL CALIFORNIA, USA. AB - Ecoclub youth and supervising family members conducted citizen science to assess regional prevalence and distribution of Batrachochytrium dendrobatidis (Bd) among amphibians at Humboldt Bay National Wildlife Refuge (Refuge) and Redwood National and State Parks (Parks), Humboldt County, California, US, May 2013 through December 2014. Using quantitative real-time PCR, 26 (17%) of 155 samples were positive for Bd. Positive samples occurred in four frog and toad species: foothill yellow-legged frog ( Rana boylii ), northern red-legged frog ( Rana aurora ), Pacific chorus frog ( Pseudacris regilla ), and western toad (Anaxyrus [Bufo] boreas); no salamanders or anuran larvae were positive. Except for R. aurora , all infected anurans were first-time species reports for coastal northern California. At the Refuge, significantly fewer (6/71) postmetamorphic amphibians were positive compared to the Parks (20/69; P=0.0018). We assessed the association of being PCR-positive for Bd, season of sampling, and age of sampler (child, teen, or adult). The full model with season, species, and sampler age had the greatest support. Frogs tested in winter or spring were more likely to be positive than those tested in summer or fall; foothill yellow-legged frogs, northern red-legged frogs, and western toads were more likely to be positive than were Pacific chorus frogs; and the probability of being positive nearly doubled when a child (<=12 yr old) collected the sample compared to a teen or adult. Our results support other chytrid studies that found amphibians are more susceptible to Bd when temperatures are cool and that species differ in their susceptibility. The Ecoclub's findings provide new information important to conservation of northern California's coastal amphibians and demonstrate the value of involving children in citizen science. PMID- 27195683 TI - PREVALENCE OF ANTIBODIES FOR SELECTED CANINE PATHOGENS AMONG WOLVES (CANIS LUPUS) FROM THE ALASKA PENINSULA, USA. AB - We collected blood samples from wolves ( Canis lupus ) on the Alaska Peninsula, southwest Alaska, US, 2006-11 and tested sera for antibodies to canine adenovirus (CAV), canine coronavirus (CCV), canine distemper virus (CDV), canine herpesvirus (CHV), canine parainfluenza (CPI), canine parvovirus (CPV), Neospora caninum , and Toxoplasma gondii . Detected antibody prevalence was 90% for CAV, 28% for CCV, 12% for CDV, 93% for CHV, 0% for CPI, 20% for CPV, 0% for N. caninum, and 86% for T. gondii . Prevalence of CCV antibodies suggested a seasonal pattern with higher prevalence during spring (43%) than in fall (11%). Prevalence of CCV antibodies also declined during the 6-yr study with high prevalence during spring 2006-08 (80%, n=24) and low prevalence during spring 2009-11 (4%, n=24). Prevalence of N. caninum and T. gondii antibodies were highly variable in the study area during 2006-11. Results suggested that some pathogens might be enzootic on the Alaska Peninsula (e.g., CAV and CHV) while others may be epizootic (e.g., CCV, N. caninum , T. gondii ). PMID- 27195682 TI - MODE OF ATTACHMENT AND PATHOLOGY CAUSED BY PARORCHITES ZEDERI IN THREE SPECIES OF PENGUINS: PYGOSCELIS PAPUA, PYGOSCELIS ADELIAE, AND PYGOSCELIS ANTARCTICA IN ANTARCTICA. AB - We identified and compared gross and microscopic lesions associated with the cestode, Parorchites zederi, in the digestive tracts of three species of penguins (Spheniscidae): the Chinstrap ( Pygoscelis antarctica ), Gentoo ( Pygoscelis papua ), and Adelie penguins ( Pygoscelis adeliae ). The gastrointestinal tracts of 79 recently dead individuals (71 chicks and eight adults) were collected in locations throughout the Antarctic Peninsula during summer field trips in 2006 09. Parorchites zederi was found in the small intestine of 37 animals (47%), and 23 (62%) of these had parasite-associated lesions. The cestodes were either free in the intestinal lumen, clustered within mucosal ulcers, or deeply embedded in the intestinal wall. Histopathologic changes were most severe in adult Gentoo Penguins and included transmural fibrogranulomatous enteritis, hemorrhage, and edema. This report of pathology associated with P. zederi in the digestive tracts of penguins can serve as reference to monitor health in Antarctic birds associated with environmental changes. PMID- 27195679 TI - Myt3 suppression sensitizes islet cells to high glucose-induced cell death via Bim induction. AB - Diabetes is a chronic disease that results from the body's inability to properly control circulating blood glucose levels. The loss of glucose homoeostasis can arise from a loss of beta-cell mass because of immune-cell-mediated attack, as in type 1 diabetes, and/or from dysfunction of individual beta-cells (in conjunction with target organ insulin resistance), as in type 2 diabetes. A better understanding of the transcriptional pathways regulating islet-cell survival is of great importance for the development of therapeutic strategies that target beta-cells for diabetes. To this end, we previously identified the transcription factor Myt3 as a pro-survival factor in islets following acute suppression of Myt3 in vitro. To determine the effects of Myt3 suppression on islet-cell survival in vivo, we used an adenovirus to express an shRNA targeting Myt3 in syngeneic optimal and marginal mass islet transplants, and demonstrate that suppression of Myt3 impairs the function of marginal mass grafts. Analysis of grafts 5 weeks post-transplant revealed that grafts transduced with the shMyt3 adenovirus contained ~20% the number of transduced cells as grafts transduced with a control adenovirus. In fact, increased apoptosis and significant cell loss in the shMyt3-transduced grafts was evident after only 5 days, suggesting that Myt3 suppression sensitizes islet cells to stresses present in the early post transplant period. Specifically, we find that Myt3 suppression sensitizes islet cells to high glucose-induced cell death via upregulation of the pro-apoptotic Bcl2 family member Bim. Taken together these data suggest that Myt3 may be an important link between glucotoxic and immune signalling pathways. PMID- 27195684 TI - HELMINTH INFECTIONS IN NORTHERN BOBWHITES (COLINUS VIRGINIANUS) FROM A LEGACY LANDSCAPE IN TEXAS, USA. AB - The Northern Bobwhite ( Colinus virginianus ) has declined across its range. The primary cause of this decline is thought to be habitat loss and fragmentation. However, there is speculation that factors such as parasites may play a role. South Texas recently was designated a Legacy Landscape of National Significance for Northern Bobwhite Conservation and is a region with some of the highest bobwhite densities in the US. Limited studies on bobwhite parasites have been conducted in this crucial landscape. We documented helminth parasites infecting bobwhites in South Texas, identified those that are known to be pathogenic to quail, documented pathologic responses to infection, and evaluated infections related to host intrinsic and extrinsic factors. We examined 209 bobwhites and found nine species of helminths including two known to cause tissue damage in bobwhites: Tetrameres pattersoni and Oxyspirura petrowi. The cecal nematode Aulonocephalus pennula was numerically dominant and had the greatest prevalence, intensity, and abundance. Prevalence and abundance of A. pennula were significantly greater in adult than juvenile bobwhites, whereas host sex was not an important factor. Prevalence of A. pennula was significantly greater during the 2012-13 hunting season than the 2013-14 season. The abundance of A. pennula also was significantly greater in bobwhites with greater mass within each age cohort. This research provides insight regarding the factors that influence helminth infections in bobwhites from South Texas and highlights the importance of broad-scale surveys when assessing helminth infections across large regions. PMID- 27195686 TI - ESTIMATING CONTACT RATES OF HAWAIIAN MONK SEALS (NEOMONACHUS SCHAUINSLANDI) USING SOCIAL NETWORK ANALYSIS. AB - Understanding disease transmission dynamics, which are in part mediated by rates and patterns of social contact, is fundamental to predicting the likelihood, rate of spread, impacts, and mitigation of disease outbreaks in wildlife populations. Contact rates, which are important parameters required for epidemiologic models, are difficult to estimate. The endangered Hawaiian monk seal (Neomonachus schauinslandi) may be particularly vulnerable to morbillivirus outbreaks, due to its low abundance, lack of genetic diversity, and history of isolation from mammalian diseases. Morbillivirus epizootics have had devastating effects on other seal populations. We constructed social networks based on visual observations of individually identifiable monk seals associating onshore to estimate contact rates, assuming random mixing, and also to investigate contact patterns of different age and sex classes. Contact rates estimated from two island populations in 4 yr were remarkably similar, indicating any two individuals have about a one in 1,000 chance of making contact on any given day. Further, contact patterns within and among age and sex classes were statistically different from random. The methods we used could be broadly applied to empirically derive contact rates using association data. These rates are critical for epidemiologic modelling to simulate wildlife disease outbreaks and to inform science-based prevention and mitigation programs. PMID- 27195685 TI - PREVALENCE OF ANTIBODIES TO SELECTED VIRUSES AND PARASITES IN INTRODUCED AND ENDEMIC CARNIVORES IN WESTERN MADAGASCAR. AB - Introduced animals impact endemic populations through predation, competition, and disease transmission. Populations of endemic carnivores in Madagascar are declining, and pathogens transmitted from introduced species may further endanger these unique species. We assessed the exposure of introduced and endemic carnivores to common viral and parasitic pathogens in two national parks of Madagascar (Kirindy Mitea National Park and Ankarafantsika National Park) and their neighboring villages. We also identified variables associated with the presence of antibodies to these pathogens in fosa ( Cryptoprocta ferox ). Introduced and endemic species were exposed to canine parvovirus, canine herpesvirus, feline calicivirus, and Toxoplasma gondii . Domestic dogs ( Canis familiaris ) and cats ( Felis catus ) may be sources of infection for these pathogens. Prevalence of antibodies to Toxoplasma in captured fosa was >93%, and adults were more likely to be exposed than immature individuals. Our data provide a basis upon which to evaluate and manage risks of pathogen transmission between species. PMID- 27195687 TI - PATTERNS OF MYCOBACTERIUM LEPRAE INFECTION IN WILD NINE-BANDED ARMADILLOS (DASYPUS NOVEMCINCTUS) IN MISSISSIPPI, USA. AB - The nine-banded armadillo ( Dasypus novemcinctus ) is the only known nonhuman reservoir of Mycobacterium leprae , the causative agent of Hansen's disease or leprosy. We conducted a 6-yr study on a wild population of armadillos in western Mississippi that was exposed to M. leprae to evaluate the importance of demographic and spatial risk factors on individual antibody status. We found that spatially derived covariates were not predictive of antibody status. Furthermore, analyses revealed no evidence of clustering by antibody-positive individuals. Lactating females and adult males had higher odds of being antibody positive than did nonlactating females. No juveniles or yearlings were antibody positive. Results of these analyses support the hypothesis that M. leprae infection patterns are spatially homogeneous within this armadillo population. Further research related to movement patterns, contact among individuals, antibody status, and environmental factors could help address hypotheses related to the role of environmental transmission on M. leprae infection and the mechanisms underlying the differential infection patterns among demographic groups. PMID- 27195688 TI - EYEWORMS (OXYSPIRURA PETROWI) IN NORTHERN BOBWHITES (COLINUS VIRGINIANUS) FROM THE ROLLING PLAINS ECOREGION OF TEXAS AND OKLAHOMA, 2011-13. AB - The Northern Bobwhite ( Colinus virginianus ) has been steadily declining throughout much of its historic range for decades. The Rolling Plains ecoregion of Texas and western Oklahoma, historically rich with wild Northern Bobwhites and one of the last remaining quail strongholds, also has a declining population. During August and October in 2011-13, 348 Northern Bobwhites from the Rolling Plains were examined for eyeworms (Oxyspirura petrowi). Of these 348 Northern Bobwhites, 144 (41.4%) were infected with 1,018 total eyeworms. Eyeworm abundance (mean+/-SE) was 2.9+/-0.4 (range 0-64), with an intensity (mean+/-SE) of 7.1+/ 0.6. Eyeworm prevalence was significantly higher in adult Northern Bobwhites (58.7%) than in juveniles (35.4%). Recent research suggests that eyeworms have the potential to cause cellular tissue damage to the eye, but it is unknown how these worms affect host survivability. This study further expands the regional distribution of O. petrowi in Northern Bobwhites in the Rolling Plains ecoregion and assesses the prevalence and abundance of infection across host age, host sex, and year. Further research is warranted on the life history of O. petrowi and assessing the impacts of eyeworms on their definitive host at individual and population levels. PMID- 27195689 TI - A RETROSPECTIVE STUDY OF CAUSES OF SKIN LESIONS IN WILD TURKEYS (MELEAGRIS GALLOPAVO) IN THE EASTERN USA, 1975-2013. AB - Skin lesions of Wild Turkeys ( Meleagris gallopavo ) are a common cause of concern to wildlife biologists and the general public and are a frequent reason for submission to diagnostic laboratories. The purpose of this retrospective study is to evaluate the causes, occurrence, and epidemiologic patterns of skin lesions in Wild Turkeys in the eastern US. Skin lesions were diagnosed in 30% (n=199) of the 660 Wild Turkey samples submitted to the Southeastern Cooperative Wildlife Disease Study diagnostic service from 1975 to 2013. Avian pox was the most frequent cause of skin lesions (66%, n=131), followed by bacterial dermatitis (22%, n=44), ectoparasitism-related dermatitis (3%, n=6), fungal dermatitis (2.5%, n=5), and neoplasia (2.0%, n=4). Although the gross appearance of skin lesions is often insufficient to determine the etiology, the anatomic distribution of lesions and temporal occurrence of certain diseases may offer insights into likely causes. Cases with lesions involving or restricted to the head and neck were much more likely to be caused by avian pox than other etiologies. Similarly, lesions restricted to the feet were more likely to be of bacterial origin. Skin lesions observed in the fall and winter were more likely to be caused by avian pox, whereas bacterial dermatitis was more frequently observed in the spring and summer. This retrospective study provides a summary of the causes of skin lesions in Wild Turkeys and serves as a useful reference to diagnosticians and biologists when evaluating Wild Turkeys with skin lesions. PMID- 27195690 TI - DEVELOPMENT OF REFERENCE RANGES FOR PLASMA TOTAL CHOLINESTERASE AND BRAIN ACETYLCHOLINESTERASE ACTIVITY IN FREE-RANGING CARNABY'S BLACK-COCKATOOS (CALYPTORHYNCHUS LATIROSTRIS). AB - Published avian reference ranges for plasma cholinesterase (ChE) and brain acetylcholinesterase (AChE) are numerous. However, a consistently reported recommendation is the need for species- and laboratory-specific reference ranges because of variables, including assay methods, sample storage conditions, season, and bird sex, age, and physiologic status. We developed normal reference ranges for brain AChE and plasma total ChE (tChE) activity for Carnaby's Black-Cockatoos (Calyptorhynchus latirostris) using a standardized protocol (substrate acetylthiocholine at 25 C). We report reference ranges for brain AChE (19-41 MUmol/min per g, mean 21+/-6.38) and plasma tChE (0.41-0.53 MUmol/min per mL, mean 0.47+/-0.11) (n=15). This information will be of use in the ongoing field investigation of a paresis-paralysis syndrome in the endangered Carnaby's Black Cockatoos, suspected to be associated with exposure to anticholinesterase compounds and add to the paucity of reference ranges for plasma tChE and brain AChE in Australian psittacine birds. PMID- 27195691 TI - Photobasicity in Quinolines: Origin and Tunability via the Substituents' Hammett Parameters. PMID- 27195692 TI - An Improved DINEOF Algorithm for Filling Missing Values in Spatio-Temporal Sea Surface Temperature Data. AB - In this study, an improved Data INterpolating Empirical Orthogonal Functions (DINEOF) algorithm for determination of missing values in a spatio-temporal dataset is presented. Compared with the ordinary DINEOF algorithm, the iterative reconstruction procedure until convergence based on every fixed EOF to determine the optimal EOF mode is not necessary and the convergence criterion is only reached once in the improved DINEOF algorithm. Moreover, in the ordinary DINEOF algorithm, after optimal EOF mode determination, the initial matrix with missing data will be iteratively reconstructed based on the optimal EOF mode until the reconstruction is convergent. However, the optimal EOF mode may be not the best EOF for some reconstructed matrices generated in the intermediate steps. Hence, instead of using asingle EOF to fill in the missing data, in the improved algorithm, the optimal EOFs for reconstruction are variable (because the optimal EOFs are variable, the improved algorithm is called VE-DINEOF algorithm in this study). To validate the accuracy of the VE-DINEOF algorithm, a sea surface temperature (SST) data set is reconstructed by using the DINEOF, I-DINEOF (proposed in 2015) and VE-DINEOF algorithms. Four parameters (Pearson correlation coefficient, signal-to-noise ratio, root-mean-square error, and mean absolute difference) are used as a measure of reconstructed accuracy. Compared with the DINEOF and I-DINEOF algorithms, the VE-DINEOF algorithm can significantly enhance the accuracy of reconstruction and shorten the computational time. PMID- 27195694 TI - Characterization and Screening of Native Scenedesmus sp. Isolates Suitable for Biofuel Feedstock. AB - In current study isolates of two native microalgae species were screened on the basis of growth kinetics and lipid accumulation potential. On the basis of data obtained on growth parameters and lipid accumulation, it is concluded that Scenedesmus dimorphus has better potential as biofuel feedstock. Two of the isolates of Scenedesmus dimorphus performed better than other isolates with respect to important growth parameters with lipid content of ~30% of dry biomass. Scenedesmus dimorphus was found to be more suitable as biodiesel feedstock candidate on the basis of cumulative occurrence of five important biodiesel fatty acids, relative occurrence of SFA (53.04%), MUFA (23.81%) and PUFA (19.69%), and more importantly that of oleic acid in its total lipids. The morphological observations using light and Scanning Electron Microscope and molecular characterization using amplified 18S rRNA gene sequences of microalgae species under study were also performed. Amplified 18S rRNA gene fragments of the microalgae species were sequenced, annotated at the NCBI website and phylogenetic analysis was done. We have published eight 18S rRNA gene sequences of microalgae species in NCBI GenBank. PMID- 27195693 TI - Hands-Off Time for Endotracheal Intubation during CPR Is Not Altered by the Use of the C-MAC Video-Laryngoscope Compared to Conventional Direct Laryngoscopy. A Randomized Crossover Manikin Study. AB - INTRODUCTION: Sufficient ventilation and oxygenation through proper airway management is essential in patients undergoing cardio-pulmonary resuscitation (CPR). Although widely discussed, securing the airway using an endotracheal tube is considered the standard of care. Endotracheal intubation may be challenging and causes prolonged interruption of chest compressions. Videolaryngoscopes have been introduced to better visualize the vocal cords and accelerate intubation, which makes endotracheal intubation much safer and may contribute to intubation success. Therefore, we aimed to compare hands-off time and intubation success of direct laryngoscopy with videolaryngoscopy (C-MAC, Karl Storz, Tuttlingen, Germany) in a randomized, cross-over manikin study. METHODS: Twenty-six anesthesia residents and twelve anesthesia consultants of the University Hospital Zurich were recruited through a voluntary enrolment. All participants performed endotracheal intubation using direct laryngoscopy and C-MAC in a random order during ongoing chest compressions. Participants were strictly advised to stop chest compression only if necessary. RESULTS: The median hands-off time was 1.9 seconds in direct laryngoscopy, compared to 3 seconds in the C-MAC group. In direct laryngoscopy 39 intubation attempts were recorded, resulting in an overall first intubation attempt success rate of 97%, compared to 38 intubation attempts and 100% overall first intubation attempt success rate in the C-MAC group. CONCLUSION: As a conclusion, the results of our manikin-study demonstrate that video laryngoscopes might not be beneficial compared to conventional, direct laryngoscopy in easily accessible airways under CPR conditions and in experienced hands. The benefits of video laryngoscopes are of course more distinct in overcoming difficult airways, as it converts a potential "blind intubation" into an intubation under visual control. PMID- 27195695 TI - Identifying Liver Cancer and Its Relations with Diseases, Drugs, and Genes: A Literature-Based Approach. AB - In biomedicine, scientific literature is a valuable source for knowledge discovery. Mining knowledge from textual data has become an ever important task as the volume of scientific literature is growing unprecedentedly. In this paper, we propose a framework for examining a certain disease based on existing information provided by scientific literature. Disease-related entities that include diseases, drugs, and genes are systematically extracted and analyzed using a three-level network-based approach. A paper-entity network and an entity co-occurrence network (macro-level) are explored and used to construct six entity specific networks (meso-level). Important diseases, drugs, and genes as well as salient entity relations (micro-level) are identified from these networks. Results obtained from the literature-based literature mining can serve to assist clinical applications. PMID- 27195696 TI - The impact of a medication review with follow-up service on hospital admissions in aged polypharmacy patients. AB - AIMS: The aims were to assess the impact of a medication review with follow-up (MRF) service provided in community pharmacy to aged polypharmacy patients on the number of medication-related hospital admissions and to estimate the effect on hospital costs. METHODS: This was a sub-analysis of a cluster randomized controlled trials carried out in 178 community pharmacies in Spain. Pharmacies in the intervention group (IG) provided a comprehensive medication review during 6 months. Pharmacists in the comparison group (CG) delivered usual care. For the purposes of this sub-analysis, an expert panel of three internal medicine specialists screened the hospitalizations occurring during the main study, in order to identify medication-related hospitalizations. Inter-rater reliability was measured using Fleiss's kappa. Hospital costs were calculated using diagnosis related groups. RESULTS: One thousand four hundred and three patients were included in the main study and they had 83 hospitalizations. Forty-two hospitalizations (50.6%) were medicine-related, with a substantial level of agreement among the experts (kappa = 0.65, 95% CI 0.52, 0.78, P < 0.01). The number of medication-related hospitalizations was significantly lower in patients receiving MRF (IG 11, GC 31, P = 0.042). The probability of being hospitalized was 3.7 times higher in the CG (odds ratio 3.7, 95% CI 1.2, 11.3, P = 0.021). Costs for a medicine-related hospitalization were ?6672. Medication-related hospitalization costs were lower for patients receiving MRF [IG: ?94 (SD 917); CG: ?301 (SD 2102); 95% CI 35.9, 378.0, P = 0.018]. CONCLUSION: MRF provided by community pharmacists might be an effective strategy to balance the assurance of the benefit from medications and the avoidance of medication-related hospitalizations in aged patients using polypharmacy. PMID- 27195697 TI - The Cohort Study on Prediction of Incidence of All-Cause Mortality by Metabolic Syndrome. AB - AIM: The aim was to evaluate the impact of metabolic syndrome (MS), MS individual components and 32 kinds of MS specific component combinations on all-cause mortality risk in a fixed cohort of MJ check-up population. METHODS: We observed the events of death in a fixed cohort, where the population was composed of 45,542 individuals aged 35-74 who were examined at MJ Health check-up Center in 1997 as baseline examination, and were followed up to 2005. Median duration of follow-up was 7.44 years. MS was defined according to the National Cholesterol Educational Program (the revised NCEP-ATPIII for Asian in 2004), the prevalence of MS was standardized according to China's fifth census data. We constructed common Cox regression model, simultaneously adjusting the classic risk factors (such as age, sex, smoking, alcohol drinking, physical activity, family history, etc.) to examine the relationship between MS, MS individual components and 32 kinds of MS specific component combinations on the occurrence of death with the fixed cohort. RESULTS: The standardized prevalence of MS was 29.75% (male: 30.36%, female: 29.51%). There were 1,749 persons who died during the median 7.44 years follow-up, the mortality rate was 46 per 10,000 person years. The mortality rates were 71 and 35 per 10,000 person years for those with and without MS, respectively. After adjustment for age, sex and classical risk factors, compared with subjects without MS, the hazard ratio of all-cause mortality was 1.26 (95% CI: 1.14-1.40). The all-cause mortality were more highly significant than other combinations (P <0.05) when the following combinations exist: "elevated blood pressure", "elevated fasting plasma glucose + low high-density lipoprotein cholesterol", "elevated blood pressure + elevated triglyceride + elevated fasting plasma glucose", "elevated fasting plasma glucose + low high-density lipoprotein cholesterol + elevated blood pressure + elevated triglyceride". After adjusting age, sex and classical risk factors, the HRs for those with 0 to 5 components were 1, 1.22, 1.25, 1.33, 1.66, and 1.92, respectively. There was a significant dose-response relationship (P for liner trend <0.001) between the number of MS components and the risk of all-cause mortality in the overall fixed cohort sample. CONCLUSION: In a large scale middle-aged Taiwan check-up population, MS may be associated with a much higher risk for all-cause mortality. These results may underline the fact that MS is a non-homogeneous syndrome and have a significant impact on detecting high-risk individuals suffering from metabolic disorders for preventing and controlling death. PMID- 27195698 TI - Breast Milk from Frequent Trans Fatty Acid Consumers Shows High Triglyceride and Glucose Levels, but Low Cholesterol and Apolipoprotein A-I levels, with Resulting Impaired In Vitro Zebrafish Embryo Growth and Survival. AB - BACKGROUND: It is well known that breast milk is the best nutritional source for infant growth. However, there has been no information about the quality of breast milk from individuals who daily consume a trans fatty acid (TFA)-enriched diet. SUBJECTS AND METHODS: We performed compositional and functional analyses with breast milk from lactating mothers, in terms of lipid content and zebrafish embryo survivability, among individuals who daily consumed TFA-enriched food (n = 5), normal diet as control (n = 5), and powder formula (n = 5). RESULTS: In lipid content of breast milk, the control group showed 2.5- and 4.5-fold higher cholesterol content than the TFA group and infant formula, respectively. The TFA group and infant formula showed 1.8- and 2.0-fold higher triglyceride (TG) than the control group. Moreover, the TFA group and formula showed 1.4- and 4.8-fold higher glucose levels compared with control. The TFA group also showed 25% lower protein content than control. Microinjection with breast milk (50 nL) from the TFA group showed significantly lower zebrafish embryo survivability (50% +/- 4%) compared with the control (66% +/- 5%), whereas microinjection with formula showed the lowest survivability (39% +/- 5%) with the slowest developmental speed. Immunodetection revealed that breast milk from the TFA group showed smaller-sized apoA-I (25.5 +/- 0.6 kDa) than that from the control group (27.5 +/ 1.5 kDa), whereas formula did not contain apoA-I. Larger apoA-I size in breast milk was directly associated with higher embryo survivability. CONCLUSIONS: Breast milk from the TFA group showed increased TG and loss of cholesterol, lactalbumin (14 kDa), and apoA-I proteins, resulting in functional impairment of development and growth. PMID- 27195700 TI - Correction: Offshore Habitat Preference of Overwintering Juvenile and Adult Black Sea Bass, Centropristis striata, and the Relationship to Year-Class Success. AB - [This corrects the article DOI: 10.1371/journal.pone.0147627.]. PMID- 27195699 TI - The Splicing Efficiency of Activating HRAS Mutations Can Determine Costello Syndrome Phenotype and Frequency in Cancer. AB - Costello syndrome (CS) may be caused by activating mutations in codon 12/13 of the HRAS proto-oncogene. HRAS p.Gly12Val mutations have the highest transforming activity, are very frequent in cancers, but very rare in CS, where they are reported to cause a severe, early lethal, phenotype. We identified an unusual, new germline p.Gly12Val mutation, c.35_36GC>TG, in a 12-year-old boy with attenuated CS. Analysis of his HRAS cDNA showed high levels of exon 2 skipping. Using wild type and mutant HRAS minigenes, we confirmed that c.35_36GC>TG results in exon 2 skipping by simultaneously disrupting the function of a critical Exonic Splicing Enhancer (ESE) and creation of an Exonic Splicing Silencer (ESS). We show that this vulnerability of HRAS exon 2 is caused by a weak 3' splice site, which makes exon 2 inclusion dependent on binding of splicing stimulatory proteins, like SRSF2, to the critical ESE. Because the majority of cancer- and CS causing mutations are located here, they affect splicing differently. Therefore, our results also demonstrate that the phenotype in CS and somatic cancers is not only determined by the different transforming potentials of mutant HRAS proteins, but also by the efficiency of exon 2 inclusion resulting from the different HRAS mutations. Finally, we show that a splice switching oligonucleotide (SSO) that blocks access to the critical ESE causes exon 2 skipping and halts proliferation of cancer cells. This unravels a potential for development of new anti-cancer therapies based on SSO-mediated HRAS exon 2 skipping. PMID- 27195701 TI - Assessing Individual Intellectual Output in Scientific Research: Mexico's National System for Evaluating Scholars Performance in the Humanities and the Behavioral Sciences. AB - Assessing the research of individual scholars is currently a matter of serious concern and worldwide debate. In order to gauge the long-term efficacy and efficiency of this practice, we carried out a limited survey of the operation and outcome of Mexico's 30-year old National System of Investigators or SNI, the country's main instrument for stimulating competitive research in science and technology. A statistical random sample of researchers listed in the area of Humanities and Behavioral Sciences-one of SNI's first and better consolidated academic divisions comprising a wide range of research disciplines, from philosophy to pedagogy to archaeology to experimental brain research-was screened comparing individual ranks or "Levels of distinction" to actual compliance with the SNI's own evaluation criteria, as reflected in major public databases of scholarly production. The same analysis was applied to members of a recent Review Committee, integrated by top-level researchers belonging to that general area of knowledge, who have been in charge of assessing and ranking their colleagues. Our results for both sets of scholars show wide disparity of individual productivity within the same SNI Level, according to all key indicators officially required (books issued by prestigious publishers, research articles appeared in indexed journals, and formation of new scientists), as well as in impact estimated by numbers of citations. Statistical calculation from the data indicates that 36% of members in the Review Committee and 53% of researchers in the random sample do not satisfy the official criteria requested for their appointed SNI Levels. The findings are discussed in terms of possible methodological errors in our study, of relevance for the SNI at large in relation to independent appraisals, of the cost-benefit balance of the organization as a research policy tool, and of possible alternatives for its thorough restructuring. As it currently stands SNI is not a model for efficient and effectual national systems of research assessment. PMID- 27195703 TI - Coombs Positive Thrombotic Thrombocytopenic Purpura in a Male Pediatric Patient: An Urgent Diagnostic Challenge. AB - Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy often caused by deficiency of von Willebrand (vW) factor cleaving protease, ADAMTS-13, leading to large vW multimers and intravascular platelet aggregation. Hemolysis in TTP is mechanical and nonimmune mediated, thus Coombs testing is usually negative. We report a case of an adolescent with thrombocytopenia and Coombs positive anemia, diagnosed with Evans syndrome, but ultimately found to have TTP. TTP should be considered in children with thrombocytopenia and Coombs positive anemia who are refractory to steroids or develop signs of microangiopathy. Recognition of this presentation can lead to life-saving treatment with plasma exchange. PMID- 27195702 TI - Insights on the Optical Properties of Estuarine DOM - Hydrological and Biological Influences. AB - Dissolved organic matter (DOM) in estuaries derives from a diverse array of both allochthonous and autochthonous sources. In the estuarine system Ria de Aveiro (Portugal), the seasonality and the sources of the fraction of DOM that absorbs light (CDOM) were inferred using its optical and fluorescence properties. CDOM parameters known to be affected by aromaticity and molecular weight were correlated with physical, chemical and meteorological parameters. Two sites, representative of the marine and brackish water zones of the estuary, and with different hydrological characteristics, were regularly surveyed along two years, in order to determine the major influences on CDOM properties. Terrestrial derived compounds are the predominant source of CDOM in the estuary during almost all the year and the two estuarine zones presented distinct amounts, as well as absorbance and fluorescence characteristics. Freshwater inputs have major influence on the dynamics of CDOM in the estuary, in particular at the brackish water zone, where accounted for approximately 60% of CDOM variability. With a lower magnitude, the biological productivity also impacted the optical properties of CDOM, explaining about 15% of its variability. Therefore, climate changes related to seasonal and inter-annual variations of the precipitation amounts might impact the dynamics of CDOM significantly, influencing its photochemistry and the microbiological activities in estuarine systems. PMID- 27195704 TI - Patient Navigation for Mothers with Depression who Have Children in Head Start: A Pilot Study. AB - This study assesses the potential of social work-facilitated patient navigation to help mothers with depression engage with mental health care. We conducted a randomized pilot trial (N = 47) in Head Start-a U.S. preschool program for low income children. Seven lay navigators received training and supervision from professional social workers. After 6 months, more navigated participants engaged with a psychologist, therapist, or social worker (45% vs. 13%, 95% confidence interval [CI] [2, 57]); engaged with any provider, (55% vs. 26%, 95% CI [1, 56]); and reported having a "depression care provider" (80% vs. 41%, 95% CI [9, 65]). Community-based navigation appears feasible; however, more definitive testing is necessary. PMID- 27195706 TI - Intracranial interhemispheric osteochondrolipoma: Diagnostic and surgical challenges in an extremely rare entity. AB - Intracranial lipomas are rare developmental lesions, predominantly occurring in the interhemispheric location. Osteochondrolipoma is an extremely rare variant of lipoma with osseous and chondroid differentiation. We present a case of interhemispheric osteochondrolipoma, in a 2.5-years-old male child which was detected antenatally, in association with corpus callosum agenesis. The lesion progressively increased in size with resulting compression of surrounding structures, and was subjected to microsurgical decompression. To the best of our knowledge, this is the first case of intracranial interhemispheric osteochondrolipoma in the existing medical literature. Peculiarities of this case and the diagnostic and surgical challenges are discussed. PMID- 27195705 TI - Analysis of Paired Primary-Metastatic Hormone-Receptor Positive Breast Tumors (HRPBC) Uncovers Potential Novel Drivers of Hormonal Resistance. AB - We sought to identify genetic variants associated with disease relapse and failure to hormonal treatment in hormone-receptor positive breast cancer (HRPBC). We analyzed a series of HRPBC with distant relapse, by sequencing pairs (n = 11) of tumors (primary and metastases) at >800X. Comparative genomic hybridization was performed as well. Top hits, based on the frequency of alteration and severity of the changes, were tested in the TCGA series. Genes determining the most parsimonious prognostic signature were studied for their functional role in vitro, by performing cell growth assays in hormonal-deprivation conditions, a setting that mimics treatment with aromatase inhibitors. Severe alterations were recurrently found in 18 genes in the pairs. However, only MYC, DNAH5, CSFR1, EPHA7, ARID1B, and KMT2C preserved an independent prognosis impact and/or showed a significantly different incidence of alterations between relapsed and non relapsed cases in the TCGA series. The signature composed of MYC, KMT2C, and EPHA7 best discriminated the clinical course, (overall survival 90,7 vs. 144,5 months; p = 0.0001). Having an alteration in any of the genes of the signature implied a hazard ratio of death of 3.25 (p<0.0001), and early relapse during the adjuvant hormonal treatment. The presence of the D348N mutation in KMT2C and/or the T666I mutation in the kinase domain of EPHA7 conferred hormonal resistance in vitro. Novel inactivating mutations in KMT2C and EPHA7, which confer hormonal resistance, are linked to adverse clinical course in HRPBC. PMID- 27195709 TI - Radiation Exposure Decreases the Quantity and Quality of Cardiac Stem Cells in Mice. AB - Radiation exposure may increase cardiovascular disease risks; however, the precise molecular/cellular mechanisms remain unclear. In the present study, we examined the hypothesis that radiation impairs cardiac stem cells (CSCs), thereby contributing to future cardiovascular disease risks. Adult C57BL/6 mice were exposed to 3 Gy gamma-rays, and heart tissues were collected 24 hours later for further experiments. Although c-kit-positive cells were rarely found, radiation exposure significantly induced apoptosis and DNA damage in the cells of the heart. The ex vivo expansion of CSCs from freshly harvested atrial tissues showed a significantly lower production of CSCs in irradiated mice compared with healthy mice. The proliferative activity of CSCs evaluated by Ki-67 expression was not significantly different between the groups. However, compared to the healthy control, CSCs expanded from irradiated mice showed significantly lower telomerase activity, more 53BP1 foci in the nuclei, lower expression of c-kit and higher expression of CD90. Furthermore, CSCs expanded from irradiated mice had significantly poorer potency in the production of insulin-like growth factor-1. Our data suggest that radiation exposure significantly decreases the quantity and quality of CSCs, which may serve as sensitive bio-parameters for predicting future cardiovascular disease risks. PMID- 27195707 TI - Cluster Differentiating 36 (CD36) Deficiency Attenuates Obesity-Associated Oxidative Stress in the Heart. AB - RATIONALE: Obesity is often associated with a state of oxidative stress and increased lipid deposition in the heart. More importantly, obesity increases lipid influx into the heart and induces excessive production of reactive oxygen species (ROS) leading to cell toxicity and metabolic dysfunction. Cluster differentiating 36 (CD36) protein is highly expressed in the heart and regulates lipid utilization but its role in obesity-associated oxidative stress is still not clear. OBJECTIVE: The aim of this study was to determine the impact of CD36 deficiency on cardiac steatosis, oxidative stress and lipotoxicity associated with obesity. METHODS AND RESULTS: Studies were conducted in control (Lean), obese leptin-deficient (Lepob/ob) and leptin-CD36 double null (Lepob/obCD36-/-) mice. Compared to lean mice, cardiac steatosis, and fatty acid (FA) uptake and oxidation were increased in Lepob/ob mice, while glucose uptake and oxidation was reduced. Moreover, insulin resistance, oxidative stress markers and NADPH oxidase dependent ROS production were markedly enhanced. This was associated with the induction of NADPH oxidase expression, and increased membrane-associated p47phox, p67phox and protein kinase C. Silencing CD36 in Lepob/ob mice prevented cardiac steatosis, increased insulin sensitivity and glucose utilization, but reduced FA uptake and oxidation. Moreover, CD36 deficiency reduced NADPH oxidase activity and decreased NADPH oxidase-dependent ROS production. In isolated cardiomyocytes, CD36 deficiency reduced palmitate-induced ROS production and normalized NADPH oxidase activity. CONCLUSIONS: CD36 deficiency prevented obesity-associated cardiac steatosis and insulin resistance, and reduced NADPH oxidase-dependent ROS production. The study demonstrates that CD36 regulates NADPH oxidase activity and mediates FA-induced oxidative stress. PMID- 27195721 TI - Particle Size-Selective Assessment of Protection of European Standard FFP Respirators and Surgical Masks against Particles-Tested with Human Subjects. AB - This study was conducted to investigate the protection of disposable filtering half-facepiece respirators of different grades against particles between 0.093 and 1.61 MUm. A personal sampling system was used to particle size-selectively assess the protection of respirators. The results show that about 10.9% of FFP2 respirators and 28.2% of FFP3 respirators demonstrate assigned protection factors (APFs) below 10 and 20, which are the levels assigned for these respirators by the British Standard. On average, the protection factors of FFP respirators were 11.5 to 15.9 times greater than those of surgical masks. The minimum protection factors (PFs) were observed for particles between 0.263 and 0.384 MUm. No significant difference in PF results was found among FFP respirator categories and particle size. A strong association between fit factors and protection factors was found. The study indicates that FFP respirators may not achieve the expected protection level and the APFs may need to be revised for these classes of respirators. PMID- 27195720 TI - Development of the Arabic Spiritual Care Intervention-Provision Scale. AB - AIMS AND OBJECTIVES: This study develops a new instrument, the Spiritual Care Intervention-Provision Scale, and assesses its psychometric properties in an Arab Muslim nurse sample. The Spiritual Care Intervention-Provision Scale was developed to measure the frequency with which nurses provided aspects of spiritual care. BACKGROUND: Most of the available spiritual care instruments were developed in the West and reflect a predominantly Christian tradition. A review of the literature on spiritual care in nursing revealed that no instrument exists for measuring spiritual care interventions provided by nurses to Arab Muslim patients. DESIGN: A cross-sectional descriptive and correlational design. METHODS: Following an extensive literature search, review by an expert panel and a pilot study which included patients' views regarding aspects of spiritual care provided by nurses, the final version of the Spiritual Care Intervention Provision Scale was tested in a convenience sample of 360 Jordanian Arab Muslim nurses. Correlational and factor analysis were used. RESULTS: The internal consistency of the Spiritual Care Intervention-Provision Scale was high, with alpha coefficient of 0.85. The exploratory factor analysis supported a two-factor structure for the Spiritual Care Intervention-Provision Scale as hypothesised. A significant positive correlation between the Spiritual Care Intervention Provision Scale and religiosity was in the expected direction though small in magnitude. CONCLUSIONS: This study initiates the development of an instrument for the provision of spiritual care intervention by nurses that balances the religious and existential dimensions of spirituality. The Spiritual Care Intervention-Provision Scale exhibited acceptable evidence of internal consistency and validity among Jordanian Arab Muslim nurses. Further work was suggested to firmly establish all aspects of this new scale. RELEVANCE TO CLINICAL PRACTICE: This culturally specific instrument contributes to the evaluation of the provision of spiritual care by Jordanian Muslim nurses to their patients, to guide them in providing a comprehensive and appropriate spiritual care interventions and to examine the effect of spiritual care on various aspects of patient's quality of life. PMID- 27195708 TI - Investigation of Genetic Variation Underlying Central Obesity amongst South Asians. AB - South Asians are 1/4 of the world's population and have increased susceptibility to central obesity and related cardiometabolic disease. Knowledge of genetic variants affecting risk of central obesity is largely based on genome-wide association studies of common SNPs in Europeans. To evaluate the contribution of DNA sequence variation to the higher levels of central obesity (defined as waist hip ratio adjusted for body mass index, WHR) among South Asians compared to Europeans we carried out: i) a genome-wide association analysis of >6M genetic variants in 10,318 South Asians with focused analysis of population-specific SNPs; ii) an exome-wide association analysis of ~250K SNPs in protein-coding regions in 2,637 South Asians; iii) a comparison of risk allele frequencies and effect sizes of 48 known WHR SNPs in 12,240 South Asians compared to Europeans. In genome-wide analyses, we found no novel associations between common genetic variants and WHR in South Asians at P<5x10-8; variants showing equivocal association with WHR (P<1x10-5) did not replicate at P<0.05 in an independent cohort of South Asians (N = 1,922) or in published, predominantly European meta analysis data. In the targeted analyses of 122,391 population-specific SNPs we also found no associations with WHR in South Asians at P<0.05 after multiple testing correction. Exome-wide analyses showed no new associations between genetic variants and WHR in South Asians, either individually at P<1.5x10-6 or grouped by gene locus at P<2.5x10-6. At known WHR loci, risk allele frequencies were not higher in South Asians compared to Europeans (P = 0.77), while effect sizes were unexpectedly smaller in South Asians than Europeans (P<5.0x10-8). Our findings argue against an important contribution for population-specific or cosmopolitan genetic variants underlying the increased risk of central obesity in South Asians compared to Europeans. PMID- 27195723 TI - Philadelphia chromosome-positive acute lymphoblastic leukemia in China: a retrospective study from the Chinese Childhood Cancer Group. PMID- 27195724 TI - Intrauterine administration of human chorionic gonadotropin (hCG) for subfertile women undergoing assisted reproduction. AB - BACKGROUND: Subfertility affects 15% of couples and represents the inability to conceive naturally following 12 months of regular unprotected sexual intercourse. Assisted reproduction refers to procedures involving the in vitro handling of both human gametes and represents a key option for many subfertile couples. Most women undergoing assisted reproduction treatment will reach the stage of embryo transfer (ET) but the proportion of embryos that successfully implant following ET has remained small since the mid-1990s. Human chorionic gonadotropin (hCG) is a hormone synthesised and released by the syncytiotrophoblast and has a fundamental role in embryo implantation and the early stages of pregnancy. Intrauterine administration of synthetic or natural hCG via an ET catheter during a mock procedure around the time of ET is a novel approach that has recently been suggested to improve the outcomes of assisted reproduction. OBJECTIVES: To investigate whether the intrauterine administration of hCG around the time of ET improves the clinical outcomes in subfertile women undergoing assisted reproduction. SEARCH METHODS: We performed a comprehensive literature search of the Cochrane Gynaecology and Fertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, PsycINFO, registers of ongoing trials andreference lists of all included studies and relevant reviews (from inception to 10 November 2015), in consultation with the Cochrane Gynaecology and Fertility Group Trials Search Co-ordinator. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) evaluating intrauterine administration of hCG around the time of ET in this review irrespective of language and country of origin. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies, assessed risk of bias, extracted data from studies and attempted to contact the authors where data were missing. We performed statistical analysis using Review Manager 5 in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. We assessed evidence quality using GRADE methods. MAIN RESULTS: Twelve RCTs investigated the effect of intrauterine administration of hCG for 4038 subfertile women undergoing assisted reproduction. The intra-cavity hCG (IC-hCG) was administered in variable doses at different timings before the ET. The source of hCG was from the urine of pregnant women or from cell cultures using recombinant DNA technology.Most of the studies (9/12) were at high risk of bias in at least one of the seven domains assessed. Common problems were unclear reporting of study methods and lack of blinding. The main limitations in the overall quality of the evidence were high risk of bias and serious imprecision.For the analyses of live birth and clinical pregnancy, there was considerable heterogeneity (I(2) greater than 75%) and we did not undertake a meta-analysis. Exploration for the sources of heterogeneity identified two key pre-specified variables as important determinants: stage of ET (cleavage versus blastocyst stage) and dose of IC-hCG (less than 500 international units (IU) versus 500 IU or greater). We then performed meta analysis for these analyses within the subgroups defined by stage of embryo and dose of IC-hCG.There was an increase in live birth rate in the subgroup of women having cleavage-stage ETs with an IC-hCG dose of 500 IU or greater compared to women having cleavage-stage ETs with no IC-hCG (risk ratio (RR) 1.57, 95% confidence interval (CI) 1.32 to 1.87, three RCTs, n = 914, I(2) = 0%, moderate quality evidence). In a clinic with a live birth rate of 25% per cycle then the use of IC-hCG -500 IU or greater would be associated with a live birth rate that varies from 33% to 46%. We did not observe a significant effect on live birth in any of the other subgroups.The was an increase in clinical pregnancy rate in the subgroup of women having cleavage-stage ETs with an IC-hCG dose of 500 IU or greater compared to women having cleavage-stage ETs with no IC-hCG (RR 1.41, 95% CI 1.25 to 1.58, seven RCTs, n = 1414, I(2) = 0%, moderate quality evidence). We did not observe a significant effect on clinical pregnancy in either of the other subgroups.There was no evidence that miscarriage was influenced by intrauterine hCG administration (RR 1.09, 95% CI 0.83 to 1.43, seven RCTs, n = 3395, I(2) = 0%, very low quality evidence).Other complications reported in the included studies were ectopic pregnancy (three RCTs, n = 915, three events overall), heterotopic pregnancy (one RCT, n = 495, one event), intrauterine death (two RCTs, n = 978, 21 events) and triplets (one RCT, n = 48, three events). There was no evidence of a difference between the groups, but there were too few events to allow any conclusions to be drawn and the evidence was very low quality. AUTHORS' CONCLUSIONS: The pregnancy outcome for cleavage-stage ETs using an IC-hCG dose of 500 IU or greater is promising. However, given the small size and the variable quality of the trials and the fact that the positive finding was from a subgroup analysis, the current evidence for IC-hCG treatment does not support its use in assisted reproduction cycles. A definitive large clinical trial with live birth as the primary outcome is recommended. There was no evidence that miscarriage was influenced by intrauterine hCG administration, irrespective of embryo stage at transfer or dose of IC-hCG. There were too few events to allow any conclusions to be drawn with regard to other complications. PMID- 27195736 TI - Reinforced fixation of distal fibula fractures in elderly patients; A meta analysis of biomechanical studies. AB - BACKGROUND: There is an increasing incidence of fragility fractures of the ankle in the elderly population. The open reduction and internal fixation of these fractures is challenging, due to reduced bone stock quality as a result of osteoporosis. Biomechanical studies have shown contradicting results using reinforced constructions in the fixation of fibular fractures. We therefore performed a meta-analysis of biomechanical studies on reinforced fixation of distal fibular fractures. METHODS: A literature search was conducted utilizing three online databases considering biomechanical testing of different fixation techniques of distal fibular fractures. A meta-analysis was performed on two biomechanical outcome measures; torsional stiffness and torque to failure. FINDINGS: In a total number of 13 studies 8 different reinforcement techniques were identified. Of these studies, six compared locked lateral plating with conventional lateral plating. There were no statistically significant differences between the locking and non-locking lateral plate for torque to failure or torsional stiffness. Locked plating strength was independent from bone mineral density in four studies. An antiglide plate proved to be biomechanically superior compared to a lateral plate in one study and to a locked plate in another. INTERPRETATION: Locked lateral plates are not biomechanically superior to conventional lateral plates. However the strength of locked plating may be independent of bone mineral density and could make this technique more suitable in the fixation of severe osteoporotic fractures. PMID- 27195735 TI - Effects of training in minimalist shoes on the intrinsic and extrinsic foot muscle volume. AB - BACKGROUND: Minimalist shoes have gained popularity recently because it is speculated to strengthen the foot muscles and foot arches, which may help to resist injuries. However, previous studies provided limited evidence supporting the link between changes in muscle size and footwear transition. Therefore, this study sought to examine the effects of minimalist shoes on the intrinsic and extrinsic foot muscle volume in habitual shod runners. The relationship between participants' compliance with the minimalist shoes and changes in muscle ovolume was also evaluated. METHODS: Twenty habitual shod runners underwent a 6-month self-monitoring training program designed for minimalist shoe transition. Another 18 characteristics-matched shod runners were also introduced with the same program but they maintained running practice with standard shoes. Runners were monitored using an online surveillance platform during the program. We measured overall intrinsic and extrinsic foot muscle volume before and after the program using MRI scans. FINDINGS: Runners in the experimental group exhibited significantly larger leg (P=0.01, Cohen's d=0.62) and foot (P<0.01, Cohen's d=0.54) muscle after transition. Foot muscle growth was mainly contributed by the forefoot (P<0.01, Cohen's d=0.64) but not the rearfoot muscle (P=0.10, Cohen's d=0.30). Leg and foot muscle volume of runners in the control group remained similar after the program (P=0.33-0.95). A significant positive correlation was found between participants' compliance with the minimalist shoes and changes in leg muscle volume (r=0.51; P=0.02). INTERPRETATION: Habitual shod runners who transitioned to minimalist shoes demonstrated significant increase in leg and foot muscle volume. Additionally, the increase in leg muscle volume was significantly correlated associated with the compliance of minimalist shoe use. PMID- 27195722 TI - Role of Human Corneal Stroma-Derived Mesenchymal-Like Stem Cells in Corneal Immunity and Wound Healing. AB - Corneal tissue regeneration is of crucial importance for maintaining normal vision. We aimed to isolate and cultivate human corneal stroma-derived mesenchymal stem-like cells (CSMSCs) from the central part of cadaver corneas and study their phenotype, multipotency, role in immunity and wound healing. The isolated cells grew as monolayers in vitro, expressed mesenchymal- and stemness related surface markers (CD73, CD90, CD105, CD140b), and were negative for hematopoietic markers as determined by flow cytometry. CSMSCs were able to differentiate in vitro into fat, bone and cartilage. Their gene expression profile was closer to bone marrow-derived MSCs (BMMSCs) than to limbal epithelial stem cells (LESC) as determined by high-throughput screening. The immunosuppressive properties of CSMSCs were confirmed by a mixed lymphocyte reaction (MLR), while they could inhibit proliferation of activated immune cells. Treatment of CSMSCs by pro-inflammatory cytokines and toll-like receptor ligands significantly increased the secreted interleukin-6 (IL-6), interleukin-8 (IL-8) and C-X-C motif chemokine 10 (CXCL-10) levels, as well as the cell surface adhesion molecules. CSMSCs were capable of closing a wound in vitro under different stimuli. These cells thus contribute to corneal tissue homeostasis and play an immunomodulatory and regenerative role with possible implications in future cell therapies for treating sight-threatening corneal diseases. PMID- 27195738 TI - Induced Hypothermia Preserves the Functional Enterocyte Mass in A Porcine Multiple Trauma Model: Voluntary Retraction. PMID- 27195737 TI - Biomechanical evaluation of the simple cinch stitch for arthroscopic rotator cuff repair. AB - BACKGROUND: The tissue-suture interface is described as the most vulnerable and susceptible area in the muscle-tendon-bone construction of arthroscopic rotator cuff repair. Various stitching techniques have been described to enhance the strength, fixation and stability of the repair, but technical and biomechanical challenges remain. Purpose was to examine the biomechanical properties of the simple cinch stitch in comparison to other stitches commonly used for rotator cuff repair. METHODS: Infraspinatus tendons were harvested from sheep and split in half. The tendons were randomized into five different stitch configuration groups for biomechanical testing: simple stitch; horizontal stitch; FiberChain(r); simple cinch stitch; and modified Mason-Allen stitch. Each specimen was first cyclically loaded on a universal materials testing machine under force control from 5 to 30N at 0.25Hz for twenty cycles. Then, each specimen was loaded to failure under displacement control at a rate of 1mm/s. Cyclic elongation, peak-to-peak displacement and ultimate tensile load were measured. The type of failure was recorded. FINDINGS: No differences in cyclic elongation or peak-to-peak displacement were seen between stitch configurations. In the load-to-failure test, the simple cinch stitch demonstrated significantly higher ultimate load than the simple and the horizontal stitch configurations. The comparison to the FiberChain(r) Suture revealed no statistical significant differences. The FiberChain(r) Suture demonstrated significantly higher ultimate load than the simple stitch. No statistical significance could be demonstrated in comparison to the horizontal stitch or the simple cinch stitch. The ultimate tensile load of the modified Mason-Allen stitch was significantly higher than that of the other stitch configurations. INTERPRETATION: The simple cinch stitch has an ultimate tensile load comparable to the FiberChain(r) suture and is superior to the simple stitch and the horizontal stitch. The major advantage of the simple cinch technique is that it is possible to perform the stitch entirely arthroscopically, without the need to perforate the tissue a second time or to use special suture materials. STUDY DESIGN: Controlled laboratory study. PMID- 27195740 TI - An Organolanthanide Building Block Approach to Single-Molecule Magnets. AB - Single-molecule magnets (SMMs) are highly sought after for their potential application in high-density information storage, spintronics, and quantum computing. SMMs exhibit slow relaxation of the magnetization of purely molecular origin, thus making them excellent candidates towards the aforementioned applications. In recent years, significant focus has been placed on the rare earth elements due to their large intrinsic magnetic anisotropy arising from the near degeneracy of the 4f orbitals. Traditionally, coordination chemistry has been utilized to fabricate lanthanide-based SMMs; however, heteroatomic donor atoms such as oxygen and nitrogen have limited orbital overlap with the shielded 4f orbitals. Thus, control over the anisotropic axis and induction of f-f interactions are limited, meaning that the performance of these systems can only extend so far. To this end, we have placed considerable attention on the development of novel SMMs whose donor atoms are conjugated hydrocarbons, thereby allowing us to perturb the crystal field of lanthanide ions through the use of an electronic pi-cloud. This approach allows for fine tuning of the anisotropic axis of the molecule, allowing this method the potential to elicit SMMs capable of reaching much larger values for the two vital performance measurements of an SMM, the energy barrier to spin reversal (Ueff), and the blocking temperature of the magnetization (TB). In this Account, we describe our efforts to exploit the inherent anisotropy of the late 4f elements; namely, Dy(III) and Er(III), through the use of cyclooctatetraenyl (COT) metallocenes. With respect to the Er(III) derivatives, we have seen record breaking success, reaching blocking temperatures as high as 14 K with frozen solution magnetometry. These results represent the first example of such a high TB being observed for a system with only a single spin center, formally known as a single-ion magnet (SIM). Our continued interrelationship between theoretical and experimental chemistry allows us to shed light on the mechanisms and electronic properties that govern the slow relaxation dynamics inherent to this unique set of SMMs, thus providing insight into the role by which both symmetry and crystal field effects contribute to the magnetic properties. As we look to the future success of such materials in practical devices, we must gain an understanding of how the 4f elements communicate magnetically, a subject upon which there is still limited knowledge. As such, we have described our work on coupling mononuclear metallocenes to generate new dinuclear SMMs. Through a building block approach, we have been able to gain access to new double,- triple- and quadruple-decker complexes that possess remarkable properties; exhibiting TB of 12 K and Ueff above 300 K. Our goal is to develop a fundamental platform from which to study 4f coupling, while maintaining and enhancing the strict axiality of the anisotropy of the 4f ions. This Account will present a successful strategy employed in the production of novel and high-performing SMMs, as well as a clear overview of the lessons learned throughout. PMID- 27195739 TI - The Inhibition of Mast Cell Activation of Radix Paeoniae alba Extraction Identified by TCRP Based and Conventional Cell Function Assay Systems. AB - Chinese herbs have long been used to treat allergic disease, but recently the development was greatly impeded by the lack of good methods to explore the mechanism of action. Here, we showed the effects of Chinese herb Radix Paeoniae alba were identified and characterized by a mast cell activation assay that involves electronic impedance readouts for dynamic monitoring of cellular responses to produce time-dependent cell responding profiles (TCRPs), and the anti-allergic activities were further confirmed with various conventional molecular and cell biology tools. We found Radix P. alba can dose-dependently inhibit TCPRs, and have anti-allergic function in vitro and in vivo. Radix P. alba suppressed mast cell degranulation not only inhibiting the translocation of granules to the plasma membrane, but also blocking membrane fusion and exocytosis; and that there may be other anti-allergic components in addition to paeoniflorin. Our results suggest that Radix P. alba regulated mast cell activation with multiple targets, and this approach is also suitable for discovering other mast cell degranulation-targeting Chinese herbs and their potential multi-target mechanisms. PMID- 27195741 TI - Ramp Study Hemodynamics, Functional Capacity, and Outcome in Heart Failure Patients with Continuous-Flow Left Ventricular Assist Devices. AB - Ramp studies-measuring changes in cardiac parameters as a function of serial pump speed changes (revolutions per minute [rpm])-are increasingly used to evaluate function and malfunction of continuous-flow left ventricular assist devices (CF LVADs). We hypothesized that ramp studies can predict functional capacity, quality of life (QOL), and survival in CF-LVAD patients. Hemodynamic changes per Deltarpm were measured at a minimum of CF-LVAD support, at baseline pump speed, and at maximal tolerable pump speed. Subsequently functional capacity and QOL were assessed. Eighty ramp tests were performed in 44 patients (HeartMate II, Thoratec Corporation, Pleasanton, CA). Functional status was evaluated in 70% (31/44); average 6 minute walk test (6MWT) was 312 +/- 220 min, New York Heart Association (NYHA) I-II/III-IV (70/30%) and activity scores very low-low/moderate very high (55/45%). Decrease in pulmonary capillary wedge pressure per Deltarpm was related to better NYHA classification; NYHA I-II vs. III-IV, -0.29 +/- 0.15 vs. -0.09 +/- 0.16 mm Hg/rpm * 10 (p = 0.007) as well as to activity score; very low-low vs. moderate-very high, -0.16 +/- 0.16 vs. -0.31 +/- 0.16 mm Hg/rpm * 10 (p = 0.02). Cardiac output change per Deltarpm was correlated to measures of QOL. Ramp tests did not predict survival. In conclusion, hemodynamic changes during ramp studies are associated with measures of functional capacity and QOL. Hence, such tests could potentially identify patients in risk of failure to thrive during CF-LVAD support. PMID- 27195742 TI - Design Rationale and Preclinical Evaluation of the HeartMate 3 Left Ventricular Assist System for Hemocompatibility. AB - The HeartMate 3 (HM3) left ventricular assist device (LVAD) is designed to support advanced heart failure patients. This centrifugal flow pump has a magnetically levitated rotor, artificial pulse, textured blood-contacting surfaces, optimized fluid dynamics, large blood-flow gaps, and low shear stress. Preclinical tests were conducted to assess hemocompatibility. A computational fluid dynamics (CFD) model guided design for low shear stress and sufficient washing. Hemolysis testing was conducted on six pumps. Plasma-free hemoglobin (PfHb) and modified index of hemolysis (MIH) were compared with HeartMate II (HMII). CFD showed secondary flow path residence times between 27 and 798 min, comparable with main flow residence times between 118 and 587 min; HM3 vs. HMII shear stress exposure above 150 Pa was 3.3 vs. 11 mm within the pump volume and 134 vs. 604 mm on surfaces. In in vitro hemolysis tests at 2, 5, and 10 L/min, average pfHb 6 hours after test initiation was 58, 74, and 157 mg/dl, compared with 112, 123, and 353 mg/dl for HMII. The HM3/HMII ratio of average MIH at 2, 5, and 10 L/min was 0.29, 0.36, and 0.22. Eight 60 day bovine implants were tested with average flow rates from 5.6 to 6.4 L/min with no device failures, thrombosis, or hemolysis. Results support advancing HM3 to clinical trials. PMID- 27195743 TI - Noncardiac Surgery: Some Care During Mechanical Circulatory Support Should Not Be Shared. PMID- 27195744 TI - Prevalence of De Novo Aortic Valve Insufficiency in Patients After HeartWare VAD Implantation with an Intermittent Low-Speed Algorithm. AB - De novo aortic valve insufficiency (AI) is a frequent occurrence in patients supported with left ventricular assist device (LVAD). The European version of the HeartWare LVAD has intermittent low-speed software (lavare cycle) to facilitate intermittent aortic valve opening. We examined aortic valve opening status and prevalence of AI in patients supported with HeartWare LVAD and activated lavare cycle. HeartWare LVAD patients were prospectively monitored using serial echocardiograms at different time points after the LVAD implantation. Inclusion criteria were patients with no > mild AI and/or no aortic valve surgery at the time of LVAD implantation and at least 60 days of support. Three of 37 patients had aortic valve surgery and were excluded from the analysis. A total of 34 patients with mean age of 57 +/- 12 years met the inclusion criteria. After median support duration of 408 days (77-1250 days), eight patients had trace/mild AI (24%) and one patient developed moderate AI (3%). An average pump flow, speed, and mean arterial pressure of 4.4 +/- 0.6 L/min, 2,585 +/- 147 rpm, and 88 +/- 11 mmHg were documented, respectively. Aortic valve opening was persistently seen in 22 patients (65%). Aortic valve opening is frequent, and the development of > mild AI seems to be rare in patients supported with HeartWare LVAD. PMID- 27195745 TI - Experimental Venoarterial Extracorporeal Membrane Oxygenation Induces Left Ventricular Dysfunction. AB - Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has experienced an increased use in acute cardiac failure. There are some reports on negative effects of VA-ECMO on cardiac function, such as left ventricular (LV) dilatation and cardiac stun, but the support in the literature is scarce. This study investigates the effects of experimental VA-ECMO on LV function in both peripheral and central cannulation. Ten pigs were randomized to VA-ECMO by either peripheral cannulation through the femoral vessels or central cannulation in the right atrium and ascending aorta. Left ventricular performance was measured with pressure-volume catheters during 5 hours of VA-ECMO. The LV end-diastolic and end systolic volumes increased comparably in both groups during ECMO. Left ventricular ejection fraction, stroke work, and maximum rate of pressure change decreased comparably in both groups as a function of time on ECMO. The site of cannulation had no impact on the LV response to ECMO. In conclusion, VA-ECMO increased LV volumes and reduced LV function, irrespective of cannulation site in this experimental model. Reduced LV ejection fraction and stroke work indicated LV dysfunction during ECMO. PMID- 27195746 TI - A Retrospective Observational Case Series of Low-Flow Venovenous Extracorporeal Carbon Dioxide Removal Use in Patients with Respiratory Failure. AB - We aimed to describe the use of venovenous extracorporeal carbon dioxide removal (ECCO2R) in patients with hypercapnic respiratory failure. We performed a retrospective case note review of patients admitted to our tertiary regional intensive care unit and commenced on ECCO2R from August 2013 to February 2015. Fourteen patients received ECCO2R. Demographic data, physiologic data (including pH and partial pressure of carbon dioxide in arterial blood [PaCO2]) when starting ECCO2R (t = 0), at 4 hourly intervals for the first 24 hours, then at 24 hour intervals until cessation of ECCO2R, and overall outcome were recorded. Patients are reported separately depending on whether the indication for ECCO2R was an exacerbation of chronic obstructive pulmonary disease (COPD; n = 5), or acute respiratory distress syndrome (ARDS) and persisting hypercapnoea (n = 9). Patients were managed with ECCO2R (Hemolung, ALung Inc, Pittsburgh, PA). Median duration of ECCO2R was 5 days. Four complications related to ECCO2R were reported, none resulting in serious adverse outcomes. Ten patients were discharged from intensive care unit (ICU) alive. A statistically significant improvement in pH (p = 0.012) was demonstrated. Our observational series of ECCO2R shows that this technique can be safely used to achieve therapeutic goals in patients requiring lung protection, and in COPD, in line with current publications in this area. PMID- 27195747 TI - Multicolor-Encoded Reconfigurable DNA Nanostructures Enable Multiplexed Sensing of Intracellular MicroRNAs in Living Cells. AB - Despite the widespread utilization of gold nanoparticles and graphene for in vivo applications, complex steps for the preparation and functionalization of these nanomaterials are commonly required. In addition, the cytotoxicity of such materials is currently still under debate. In this work, by taking the significant advantages of DNA in terms of biocompatibility, nontoxicity, and controllability as building blocks for DNA nanostructures, we describe the construction of a reconfigurable, multicolor-encoded DNA nanostructure for multiplexed monitoring of intracellular microRNAs (miRNAs) in living cells. The DNA nanostructure nanoprobes containing two fluorescently quenched hairpins can be obtained by simple thermal annealing of four ssDNA oligonucleotides. The presence of the target miRNAs can unfold the hairpin structures and recover fluorescent emissions at distinct wavelengths to achieve multiplexed detection of miRNAs. Importantly, the DNA nanostructure nanoprobes exhibit significantly improved stability over conventional DNA molecular beacon probes in cell lysates and can steadily enter cells to realize simultaneous detection of two types of intracellular miRNAs. The demonstration of the self-assembled DNA nanostructures for intracellular sensing thus offers great potential application of these nanoprobes for imaging, drug delivery and cancer therapy in vivo. PMID- 27195748 TI - Spontaneous Resolution of a Tracheoesophageal Fistula Caused by Button Battery Ingestion. PMID- 27195749 TI - Dot Display Affects Approximate Number System Acuity and Relationships with Mathematical Achievement and Inhibitory Control. AB - Much research has investigated the relationship between the Approximate Number System (ANS) and mathematical achievement, with continued debate surrounding the existence of such a link. The use of different stimulus displays may account for discrepancies in the findings. Indeed, closer scrutiny of the literature suggests that studies supporting a link between ANS acuity and mathematical achievement in adults have mostly measured the ANS using spatially intermixed displays (e.g. of blue and yellow dots), whereas those failing to replicate a link have primarily used spatially separated dot displays. The current study directly compared ANS acuity when using intermixed or separate dots, investigating how such methodological variation mediated the relationship between ANS acuity and mathematical achievement. ANS acuity was poorer and less reliable when measured with intermixed displays, with performance during both conditions related to inhibitory control. Crucially, mathematical achievement was significantly related to ANS accuracy difference (accuracy on congruent trials minus accuracy on incongruent trials) when measured with intermixed displays, but not with separate displays. The findings indicate that methodological variation affects ANS acuity outcomes, as well as the apparent relationship between the ANS and mathematical achievement. Moreover, the current study highlights the problem of low reliabilities of ANS measures. Further research is required to construct ANS measures with improved reliability, and to understand which processes may be responsible for the increased likelihood of finding a correlation between the ANS and mathematical achievement when using intermixed displays. PMID- 27195751 TI - The Diagnostic Challenge of Group 2 Pulmonary Hypertension. AB - Pulmonary hypertension (PH) secondary to left heart diseases associated with an increased pulmonary venous pressure is the second of a total of five groups recognized in the classification of PH. Group 2 PH is the commonest form of PH, and is associated with high morbidity and mortality. The diagnosis of group 2 PH relies on a clinical probability assessment in which echocardiography plays a major role, eventually followed by the invasive measurements of a mean pulmonary artery pressure (mPAP) >=25mmHg and a wedged PAP (PAWP) >15mmHg. This combination of mPAP and PAWP defines "post-capillary PH" (pcPH). Post-capillary PH is most often associated with a diastolic pressure gradient (DPG) or gradient between diastolic PAP and PAWP <7mmHg and/or a pulmonary vascular resistance (PVR) <=3Wood units (WU), and is called isolated pcPH (IpcPH). Postcapillary PH with a DPG >=7mmHg and/or a PVR >3WU is then combined pre- and postcapillary PH (CpcPH). Post-capillary PH is associated with a decreased survival in proportion to increased PAP and decreased right ventricular (RV) ejection fraction. CpcPH occurs in 12-13% of patients with pcPH. CpcPH is associated with pulmonary vascular remodeling and altered RV-arterial coupling. The prognosis of CpcPH is poor. PMID- 27195750 TI - Psychometric Characteristics of a Patient Reported Outcome Measure on Ego Integrity and Despair among Cancer Patients. AB - PURPOSE: To evaluate psychometric characteristics of a questionnaire (the Northwestern Ego-integrity Scale (NEIS)) on ego-integrity (the experience of wholeness and meaning in life, even in spite of negative experiences) and despair (the experience of regret about the life one has led, and feelings of sadness, failure and hopelessness) among cancer patients. METHODS: Cancer patients (n = 164) completed patient reported outcome measures on ego-integrity and despair (NEIS), psychological distress, anxiety and depression (Hospital Anxiety and Depression Scale (HADS)), and quality of life (EORTC QLQ-C30 (cancer survivors, n = 57) or EORTC QLQ-C15-PAL (advanced cancer patients, n = 107)). Confirmatory Factor Analysis was used to assess construct validity. Cronbach's alpha was used to assess internal consistency. Convergent validity was tested based on a priori defined hypotheses: a higher level of ego-integrity was expected to be related to a higher level of quality of life, and lower levels of distress, depression and anxiety; a higher level of despair was expected to be related to a lower level of quality of life, and higher levels of distress, depression and anxiety. RESULTS: The majority of all items (94.5%) of the NEIS were completed by patients and single item missing rate was below 2%. The two subscales, labeled as Ego integrity (5 items) and Despair (4 items) had acceptable internal consistency (Cronbach's alpha .72 and .61, respectively). The Ego-integrity subscale was not significantly associated with quality of life, distress, anxiety, or depression. The Despair subscale correlated significantly (p <.001) with quality of life (r = -.29), distress (r = .44), anxiety (r = .47) and depression (r = .32). CONCLUSION: The NEIS has good psychometric characteristics to assess ego integrity and despair among cancer patients. PMID- 27195752 TI - Lung Capillary Stress Failure and Arteriolar Remodelling in Pulmonary Hypertension Associated with Left Heart Disease (Group 2 PH). AB - Left heart diseases (LHD) represent the most prevalent cause of pulmonary hypertension (PH), yet there are still no approved therapies that selectively target the pulmonary circulation in LHD. The increase in pulmonary capillary pressure due to LHD is a triggering event leading to physical and biological alterations of the pulmonary circulation. Acutely, mechanosensitive endothelial dysfunction and increased capillary permeability combined with reduced fluid resorption lead to the development of interstitial and alveolar oedema. From repeated cycles of such capillary stress failure originate more profound changes with pulmonary endothelial dysfunction causing increased basal and reactive pulmonary vascular tone. This contributes to pulmonary vascular remodelling with increased arterial wall thickness, but most prominently, to alveolar wall remodelling characterized by myofibroblasts proliferation with collagen and interstitial matrix deposition. Although protective against acute pulmonary oedema, alveolar wall thickening becomes maladaptive and is responsible for the development of a restrictive lung syndrome and impaired gas exchanges contributing to shortness of breath and PH. Increasing awareness of these processes is unraveling novel pathophysiologic processes that could represent selective therapeutic targets. Thus, the roles of caveolins, of the intermediate myofilament nestin and of endothelial calcium dyshomeostasis were recently evaluated in pre-clinical models. The pathophysiology of PH due to LHD (group II PH) is distinctive from other groups of PH. Therefore, therapies targeting PH due to LHD must be evaluated in that context. PMID- 27195753 TI - Differential Action between Schisandrin A and Schisandrin B in Eliciting an Anti Inflammatory Action: The Depletion of Reduced Glutathione and the Induction of an Antioxidant Response. AB - Schisandrin A (Sch A) and schisandrin B (Sch B) are active components of Schisandrae Fructus. We compared the biochemical mechanism underlying the anti inflammatory action of Sch A and Sch B, using cultured lipopolysaccharide (LPS) stimulated RAW264.7 macrophages and concanavalin (ConA)-stimulated mouse splenocytes. Pre-incubation with Sch A or Sch B produced an anti-inflammatory action in LPS-stimulated RAW264.7 cells, as evidenced by the inhibition of the pro-inflammatory c-Jun N-terminal kinases/p38 kinase/nuclear factor-kappaB signaling pathway as well as the suppression of various pro-inflammatory cytokines and effectors, with the extent of inhibition by Sch A being more pronounced. The greater activity of Sch A in anti-inflammatory response was associated with a greater decrease in cellular reduced glutathione (GSH) level and a greater increase in glutathione S-transferase activity than corresponding changes produced by Sch B. However, upon incubation, only Sch B resulted in the activation of the nuclear factor (erythroid-derived 2)-like factor 2 and the induction of a significant increase in the expression of thioredoxin (TRX) in RAW264.7 cells. The Sch B-induced increase in TRX expression was associated with the suppression of pro-inflammatory cytokines and effectors in LPS-stimulated macrophages. Studies in a mouse model of inflammation (carrageenan-induced paw edema) indicated that while long-term treatment with either Sch A or Sch B suppressed the extent of paw edema, only acute treatment with Sch A produced a significant degree of inhibition on the inflammatory response. Although only Sch A decreased the cellular GSH level and suppressed the release of pro-inflammatory cytokines and cell proliferation in ConA-simulated splenocytes in vitro, both Sch A and Sch B treatments, while not altering cellular GSH levels, suppressed ConA stimulated splenocyte proliferation ex vivo. These results suggest that Sch A and Sch B may act differentially on activating GST/ depleting cellular GSH and inducing an antioxidant response involved in their anti-inflammatory actions. PMID- 27195756 TI - Learning to Select Supplier Portfolios for Service Supply Chain. AB - The research on service supply chain has attracted more and more focus from both academia and industrial community. In a service supply chain, the selection of supplier portfolio is an important and difficult problem due to the fact that a supplier portfolio may include multiple suppliers from a variety of fields. To address this problem, we propose a novel supplier portfolio selection method based on a well known machine learning approach, i.e., Ranking Neural Network (RankNet). In the proposed method, we regard the problem of supplier portfolio selection as a ranking problem, which integrates a large scale of decision making features into a ranking neural network. Extensive simulation experiments are conducted, which demonstrate the feasibility and effectiveness of the proposed method. The proposed supplier portfolio selection model can be applied in a real corporation easily in the future. PMID- 27195755 TI - The development of visual preferences for direct versus averted gaze faces in infant macaques (Macaca mulatta). AB - Human and nonhuman primates show a preference for looking at faces with direct gaze. In humans, this preference emerges shortly after birth, but little is known about the development of gaze preferences in monkeys. This study tracked the development of gaze preferences in infant monkeys from birth through 6 months of age using infrared eye-tracking. Although absent in the first week, a strong significant preference for direct compared to averted gaze faces emerged rapidly, peaking around 2 months of age. When looking at the eyes, the monkeys' fixations were equivalent in duration for both gaze types in the first 2 months, but thereafter remained longer for the averted gaze faces. Therefore, the infants spent a greater proportion of time overall, but made shorter fixations, when looking at the direct compared to averted gaze faces. These results suggest that monkeys develop an efficient strategy when viewing the preferred direct gaze faces that involves longer viewing times, but shorter fixations. PMID- 27195757 TI - Prioritizing government funding of adolescent vaccinations: recommendations from young people on a citizens' jury. AB - OBJECTIVE: Adolescents' views, and preferences are often over-looked when public health policies that affect them are designed and implemented. The purpose of this study was to describe young people's views and preferences for determining government funding priorities for adolescent immunization programs. METHODS: In 2015 we conducted a youth jury in metropolitan Adelaide, South Australia to deliberate on the question "What criteria should we use to decide which vaccines for young people in Australia should receive public funding?" Fifteen youth aged 15-19 years participated in the jury. Jury members were recruited from the general community through a market research company using a stratified sampling technique. RESULTS: The jury's key priorities for determining publically funded vaccines were: Disease severity - whether the vaccine preventable disease (VPD) was life threatening and impacted on quality of life. Transmissibility - VPDs with high/fast transmission and high prevalence. Demonstration of cost effectiveness, taking into account purchase price, program administration, economic and societal gain. The jury's recommendations for vaccine funding policy were strongly underpinned by the belief that it was critical to ensure that funding was targeted to not only population groups who would be medically at risk from vaccine preventable diseases, but also to socially and economically disadvantaged population groups. A novel recommendation proposed by the jury was that there should be a process for establishing criteria to remove vaccines from publically funded programs as a complement to the process for adding new vaccines. CONCLUSIONS: Young people have valuable contributions to make in priority setting for health programs and their views should be incorporated into the framing of health policies that directly affect them. PMID- 27195758 TI - Contributions and challenges for worldwide vaccine safety: The Global Advisory Committee on Vaccine Safety at 15 years. AB - In 1999, the Global Advisory Committee on Vaccine Safety (GACVS) was established by the World Health Organization (WHO) to provide independent scientific advice on issues relating to the safety of vaccines and immunization. Fifteen years onward, we conducted a multi-faceted review to evaluate the impact, reach and challenges facing GACVS, including the role GACVS plays in informing global, regional and WHO member state vaccine policy. The methods included measures of organizational structure, citation impact, themes approached, and a discussion by previous and current members to evaluate past, present and future challenges. Given the increasing range of data sources and the deployment of many new vaccines, the Committee is facing the complex task of identifying the best available evidence for recommendations on vaccine safety. To help meet the increased demand for public transparency in decision making, GACVS-structured methodology for evidence-based decisions is evolving. GACVS also promotes best practices and capacity building for timely and accurate risk assessment; risk communications; outreach to help countries maintain and, if needed, rebuild public trust in vaccines; and advocacy for bridging the major gaps in vaccine safety capacity globally. PMID- 27195754 TI - Ubr3, a Novel Modulator of Hh Signaling Affects the Degradation of Costal-2 and Kif7 through Poly-ubiquitination. AB - Hedgehog (Hh) signaling regulates multiple aspects of metazoan development and tissue homeostasis, and is constitutively active in numerous cancers. We identified Ubr3, an E3 ubiquitin ligase, as a novel, positive regulator of Hh signaling in Drosophila and vertebrates. Hh signaling regulates the Ubr3-mediated poly-ubiquitination and degradation of Cos2, a central component of Hh signaling. In developing Drosophila eye discs, loss of ubr3 leads to a delayed differentiation of photoreceptors and a reduction in Hh signaling. In zebrafish, loss of Ubr3 causes a decrease in Shh signaling in the developing eyes, somites, and sensory neurons. However, not all tissues that require Hh signaling are affected in zebrafish. Mouse UBR3 poly-ubiquitinates Kif7, the mammalian homologue of Cos2. Finally, loss of UBR3 up-regulates Kif7 protein levels and decreases Hh signaling in cultured cells. In summary, our work identifies Ubr3 as a novel, evolutionarily conserved modulator of Hh signaling that boosts Hh in some tissues. PMID- 27195759 TI - Barriers to timely administration of birth dose vaccines in The Gambia, West Africa. AB - OBJECTIVE: Although vaccine coverage in infants in sub-Saharan Africa is high, this is estimated at the age of 6-12 months. There is little information on the timely administration of birth dose vaccines. The objective of this study was to assess the timing of birth dose vaccines (hepatitis B, BCG and oral polio) and reasons for delayed administration in The Gambia. METHODS: We used vaccination data from the Farafenni Health and Demographic Surveillance System (FHDSS) between 2004 and 2014. Coverage was calculated at birth (0-1 day), day 7, day 28, 6 months and 1 year of age. Logistic regression models were used to identify demographic and socio-economic variables associated with vaccination by day 7 in children born between 2011 and 2014. RESULTS: Most of the 10,851 children had received the first dose of hepatitis B virus (HBV) vaccine by the age of 6 months (93.1%). Nevertheless, only 1.1% of them were vaccinated at birth, 5.4% by day 7, and 58.4% by day 28. Vaccination by day 7 was associated with living in urban areas (West rural: adjusted OR (AOR)=6.13, 95%CI: 3.20-11.75, east rural: AOR=6.72, 95%CI: 3.66-12.33) and maternal education (senior-educations: AOR=2.43, 95%CI: 1.17-5.06); and inversely associated with distance to vaccination delivery points (?2km: AOR=0.41, 95%CI: 0.24-0.70), and Fula ethnicity (AOR=0.60, 95%CI: 0.40-0.91). CONCLUSION: Vaccine coverage in The Gambia is high but infants are usually vaccinated after the neonatal period. Interventions to ensure the implementation of national vaccination policies are urgently needed. PMID- 27195760 TI - Improved safety of a replication-competent poxvirus-based HIV vaccine with the introduction of the HSV-TK/GCV suicide gene system. AB - INTRODUCTION: Replication-competent vaccinia viruses (VACVs) show prolonged antigen expression time and greater stimulation of immune responses than their replication-incompetent counterparts. However, there is the potential risk of serious post-vaccination complications, especially for children and immunocompromised individuals, leading to safety concerns about the reintroduction of VACV as a vaccine vector. In this study, we improved the safety of the vaccinia virus TianTan (VACV-TT) based HIV vaccine by introducing the HSV TK/GCV suicide gene system, which is composed of the herpes simplex virus type 1 thymidine kinase gene (HSV-tk) and the antiviral drug ganciclovir (GCV). MATERIALS AND METHODS: By inserting the HSV-tk gene into the replication competent VACV-TT genome, a new vector, TT-TK (VACV-TT expressing the HSV-tk gene), and a candidate vaccine, TT-EnvTK (TT-TK expressing the HIV-1 env gene), were constructed. RESULTS: The new vector TT-TK exhibited reduced replication capacity both in vitro and in vivo in the presence of GCV. GCV inhibited the replication of TT-TK in the brains of mice and skin of rabbits, and provided 100% protection in mice against lethal challenge with TT-TK at a dose of 80mg/kg/day. Furthermore, the candidate vaccine TT-EnvTK induced cellular and humoral immunity against HIV-1 antigen that was comparable to the immunity induced by VTKgpe (VACV TT expressing HIV-1 env, gag, and pol genes). DISCUSSION: These promising results suggest a new strategy to mitigate the potential risk of post-vaccination complications from replication-competent VACV-based HIV vaccines. PMID- 27195761 TI - Reduced serologic sensitivity to influenza A virus illness among inactivated influenza vaccinees. AB - We compared >=4-fold increases in antibody titers by hemagglutination inhibition assay to RT-PCR results among 42 adults with PCR-confirmed influenza A virus illnesses. Serologic sensitivity was higher among unvaccinated (69%, 95% confidence interval [CI]=48-90%) than vaccinated healthcare personnel (38%, 95% CI=29-46%) in a 2010-11 prospective cohort. PMID- 27195762 TI - Staphylococcus aureus avirulent mutant vaccine induces humoral and cellular immune responses on pregnant heifers. AB - Bovine mastitis produces economic losses, attributable to the decrease in milk production, reduced milk quality, costs of treatment and replacement of animals. A successful prophylactic vaccine against Staphylococcus aureus should elicit both humoral and cellular immune responses. In a previous report we evaluated the effectiveness of a live vaccine to protect heifers against challenge with a virulent strain. In the present study the immunological response of heifers after combined immunization schedule was investigated. In a first experimental trial, heifers were vaccinated with 3 subcutaneous doses of avirulent mutant S. aureus RC122 before calving and one intramammary dose (IMD) after calving. Antibodies concentration in blood, bactericidal effect of serum from vaccinated animals and lymphocyte proliferation was determined. The levels of total IgG, IgG1 and IgG2 in colostrum and the lymphocyte proliferation index were significantly higher in vaccinated respect to non-vaccinated group throughout the experiment. The second trial, where animals were inoculated with different vaccination schedules, was carried out to determine the effect of the IMD on the level of antibodies in blood and milk, cytokines (IL-13 and IFN-gamma) concentration and milk's SCC and bacteriology. The bacterial growth of the S. aureus strains was totally inhibited at 1-3*10(6) and 1-3*10(3)cfu/ml, when the strains were mixed with pooled serum diluted 1/40. The results shown that IMD has not a significant effect on the features determinate. In conclusion, a vaccination schedule involving three SC doses before calving would be enough to stimulate antibodies production in milk without an IMD. Furthermore, the results showed a bactericidal effect of serum from vaccinated animals and this provides further evidence about serum functionality. Immune responses, humoral (antigen-specific antibodies and Th2 type cytokines) and cellular (T-lymphocyte proliferation responses and Th1 type cytokines), were augmented by administration of the avirulent mutant which represent an antigenic pool. PMID- 27195763 TI - An Observational Study of Abstracts Presented at the American College of Veterinary Surgeon Annual Meetings (2001-2008) and Their Subsequent Full-Text Publication. AB - OBJECTIVE: To determine the frequency of abstracts presented at American College of Veterinary Surgeons (ACVS) meetings from 2001 to 2008 that were published as complete articles, to identify abstract characteristics associated with final full-text publication, and to examine consistency of information between abstracts and final full-text publications. STUDY DESIGN: Observational bibliographic study. METHODS: Abstracts were retrieved from published proceedings. Published articles were retrieved from bibliographic databases. Features of abstract and article authorship, design, and content were recorded. Regression analysis identified abstract features associated with article publication, and evaluated consistency between abstracts and final publications. RESULTS: Seven hundred eighty-two of 1078 (73%) abstracts were published as complete articles. Median time to publication was 1 year; 90% were published within 3 years. Abstracts originating from academic institutions were published more often than abstracts from practice or industry sites (odds ratio 2.61, 95% confidence interval 1.68-4.05). Compared to their conference abstracts, 49% of articles contained major inconsistences including changes in study design, interventions, outcomes, sample size, and results. For each year elapsed between presentation and publication, the odds of major inconsistency increased 2.4 times (odds ratio 2.36, 95% confidence interval 1.57-3.55) for retrospective studies and 1.4 times (odds ratio 1.35, 95% confidence interval 1.17-1.56) for other study designs. Changes in study title and authorship were frequent, particularly in publications that contained major inconsistencies. CONCLUSION: ACVS abstracts were promptly and reliably published, but final full-text publications often differed substantially from the original abstracts. PMID- 27195764 TI - Remote Monitoring of Chronic Diseases: A Landscape Assessment of Policies in Four European Countries. AB - BACKGROUND: Remote monitoring (RM) is defined as the surveillance of device transmitted outpatient data. RM is expected to enable better management of chronic diseases. The objective of this research was to identify public policies concerning RM in four European countries. METHODS: Searches of the medical literature, the Internet, and Ministry of Health websites for the United Kingdom (UK), Germany, Italy, and Spain were performed in order to identify RM policies for chronic diseases, including end stage renal disease (ESRD), chronic pulmonary obstructive disease (COPD), diabetes, heart failure, and hypertension. Searches were first performed in Q1 2014 and updated in Q4 2015. In addition, in depth interviews were conducted with payers/policymakers in each country. Information was obtained on existing policies, disease areas and RM services covered and level of reimbursement, other incentives such as quality indicators, past/current assessments of RM technologies, diseases perceived to benefit most from RM, and concerns about RM. RESULTS: Policies on RM and/or telemedicine were identified in all four countries. Pilot projects (mostly in diabetes, COPD, and/or heart failure) existed or were planned in most countries. Perceived value of RM was moderate to high, with the highest rating given for heart failure. Interviewees expressed concerns about sharing of medical information, and the need for capital investment. Patients recently discharged from hospital, and patients living remotely, or with serious and/or complicated diseases, were believed to be the most likely to benefit from RM. Formal reimbursement is scarce, but more commonly available for patients with heart failure. CONCLUSIONS: In the four European countries surveyed, RM has attracted considerable interest for its potential to increase the efficiency of healthcare for chronic diseases. Although rare at this moment, incentives to use RM technology are likely to increase in the near future as the body of evidence of clinical and/or economic benefit grows. PMID- 27195766 TI - Field-induced transition of the magnetic ground state from A-type antiferromagnetic to ferromagnetic order in CsCo2Se2. AB - We report on the magnetic properties of CsCo2Se2 with ThCr2Si2 structure, which we have characterized through a series of magnetization and neutron diffraction measurements. We find that CsCo2Se2 undergoes a phase transition to an antiferromagnetically ordered state with a Neel temperature of [Formula: see text] K. The nearest neighbour interactions are ferromagnetic as observed by the positive Curie-Weiss temperature of [Formula: see text] K. We find that the magnetic structure of CsCo2Se2 consists of ferromagnetic sheets, which are stacked antiferromagnetically along the tetragonal c-axis, generally referred to as A-type antiferromagnetic order. The observed magnitude of the ordered magnetic moment at T = 1.5 K is found to be only 0.20(1)[Formula: see text] / Co. Already in comparably small magnetic fields of [Formula: see text] T, we observe a metamagnetic transition that can be attributed to spin-rearrangements of CsCo2Se2, with the moments fully ferromagnetically saturated in a magnetic field of [Formula: see text] T. We discuss the entire experimentally deduced magnetic phase diagram for CsCo2Se2 with respect to its unconventionally weak magnetic coupling. Our study characterizes CsCo2Se2, which is chemically and electronically posed closely to the A x Fe2-y Se2 superconductors, as a host of versatile magnetic interactions. PMID- 27195765 TI - Overcoming the Refractory Expression of Secreted Recombinant Proteins in Mammalian Cells through Modification of the Signal Peptide and Adjacent Amino Acids. AB - The expression and subsequent purification of mammalian recombinant proteins is of critical importance to many areas of biological science. To maintain the appropriate tertiary structure and post-translational modifications of such proteins, transient mammalian expression systems are often adopted. The successful utilisation of these systems is, however, not always forthcoming and some recombinant proteins prove refractory to expression in mammalian hosts. In this study we focussed on the role of different N-terminal signal peptides and residues immediately downstream, in influencing the level of secreted recombinant protein obtained from suspension HEK293 cells. Using secreted alkaline phosphatase (SEAP) as a model protein, we identified that the +1/+2 downstream residues flanking a heterologous signal peptide significantly affect secreted levels. By incorporating these findings we conducted a comparison of different signal peptide sequences and identified the most productive as secrecon, a computationally-designed sequence. Importantly, in the context of the secrecon signal peptide and SEAP, we also demonstrated a clear preference for specific amino acid residues at the +1 position (e.g. alanine), and a detrimental effect of others (cysteine, proline, tyrosine and glutamine). When proteins that naturally contain these "undesirable" residues at the +1 position were expressed with their native signal peptide, the heterologous secrecon signal peptide, or secrecon with an additional alanine at the +1 or +1 and +2 position, the level of expression differed significantly and in an unpredictable manner. For each protein, however, at least one of the panel of signal peptide/adjacent amino acid combinations enabled successful recombinant expression. In this study, we highlight the important interplay between a signal peptide and its adjacent amino acids in enabling protein expression, and we describe a strategy that could enable recombinant proteins that have so far proved refractory to expression in HEK293 cells, to be produced in sufficient quantities to answer important biological questions. PMID- 27195767 TI - Asymmetries in the perception of Mandarin tones: Evidence from mismatch negativity. AB - Most investigations of the representation and processing of speech sounds focus on their segmental representations, and considerably less is known about the representation of suprasegmental phenomena (e.g., Mandarin tones). Here we examine the mismatch negativity (MMN) response to the contrast between Mandarin Tone 3 (T3) and other tones using a passive oddball paradigm. Because the MMN response has been shown to be sensitive to the featural contents of speech sounds in a way that is compatible with underspecification theories of phonological representations, here, we test the predictions of such theories regarding suprasegmental phenomena. Assuming T3 to be underspecified in Mandarin (because it has variable surface representations and low pitch), we predicted that an asymmetric MMN response would be elicited when T3 is contrasted with another tone. In 2 of our 3 experiments, this was observed, but in non-Mandarin-speaking participants as well as native speakers, suggesting that the locus of the effect was perceptual (acoustic or phonetic) rather than phonological. In a third experiment, the predicted asymmetry was limited to native speakers. These results highlight the importance of distinguishing phonological and perceptual contributions to MMN asymmetries, but also demonstrate a role of abstract phonological representations in which certain information is underspecified in long-term memory. PMID- 27195768 TI - Visuospatial working memory mediates inhibitory and facilitatory guidance in preview search. AB - Visual search is faster and more accurate when a subset of distractors is presented before the display containing the target. This "preview benefit" has been attributed to separate inhibitory and facilitatory guidance mechanisms during search. In the preview task the temporal cues thought to elicit inhibition and facilitation provide complementary sources of information about the likely location of the target. In this study, we use a Bayesian observer model to compare sensitivity when the temporal cues eliciting inhibition and facilitation produce complementary, and competing, sources of information. Observers searched for T-shaped targets among L-shaped distractors in 2 standard and 2 preview conditions. In the standard conditions, all the objects in the display appeared at the same time. In the preview conditions, the initial subset of distractors either stayed on the screen or disappeared before the onset of the search display, which contained the target when present. In the latter, the synchronous onset of old and new objects negates the predictive utility of stimulus-driven capture during search. The results indicate observers combine memory-driven inhibition and sensory-driven capture to reduce spatial uncertainty about the target's likely location during search. In the absence of spatially predictive onsets, memory-driven inhibition at old locations persists despite irrelevant sensory change at previewed locations. This result is consistent with a bias toward unattended objects during search via the active suppression of irrelevant capture at previously attended locations. (PsycINFO Database Record PMID- 27195770 TI - Epidemiological and clinical characteristics of patients infected with enterovirus D68, France, July to December 2014. AB - In 2014, the United States (US) experienced a nationwide outbreak of enterovirus D68 (EV-D68) infection with 1,152 cases reported mainly in hospitalised children with severe asthma or bronchiolitis. Following the US alert, 11 laboratories of the French enterovirus (EV) surveillance network participated in an EV-D68 survey. A total of 6,229 respiratory samples, collected from 1 July to 31 December 2014, were screened for EV-D68 resulting in 212 EV-D68-positive samples. These 212 samples corresponded to 200 EV-D68 cases. The overall EV-D68 positivity rates among respiratory samples were of 5% (184/3,645) and 1.1% (28/2,584) in hospitalised children and adults respectively. The maximum weekly EV-D68 positivity rates were of 16.1% for children (n = 24/149; week 43) and 2.6% for adults (n = 3/115; week 42). Of 173 children with EV-D68 infection alone, the main symptoms were asthma (n = 83; 48.0%) and bronchiolitis (n = 37; 21.4%). One child developed acute flaccid paralysis (AFP) following EV-D68-associated pneumonia. Although there was no significant increase in severe respiratory tract infections reported to the French public health authorities, 10.7% (19/177) of the EV-D68 infected children and 14.3% (3/21) of the EV-D68 infected adults were hospitalised in intensive care units. Phylogenetic analysis of the viral protein 1 (VP1) sequences of 179 EV-D68 cases, revealed that 117 sequences (65.4%), including that of the case of AFP, belonged to the B2 variant of clade B viruses. Continuous surveillance of EV-D68 infections is warranted and could benefit from existing influenza-like illness and EV surveillance networks. PMID- 27195769 TI - Deletion of LOX-1 Protects against Heart Failure Induced by Doxorubicin. AB - Oxidative stress is one of the major factors in doxorubicin (DOX)-induced cardiomyopathy. Lectin-like oxidized low-density lipoprotein (oxLDL) receptor-1 (LOX-1) plays an important role to regulate cardiac remodeling and oxidative stress after ischemia-reperfusion. Therefore, we examined whether or not LOX-1 contributes to the pathogenesis of DOX-induced cardiomyopathy. Cardiomyopathy was induced by a single intraperitoneal injection of DOX into wild-type (WT) mice and LOX-1 knockout (KO) mice. Echocardiography and catheter-based hemodynamic assessment apparently revealed preserved left ventricular (LV) fractional shortening (FS) and cavity size of LOX-1 KO mice compared with those of WT mice after DOX administration. Less production of tumor necrosis factor alpha (TNF alpha) and interleukin-1 beta (IL-1beta) was observed in LOX-1 KO mice than WT mice after DOX administration. Western blotting analysis also showed lower activation of nuclear factor kappaB (NF-kappaB) and p38 mitogen-activated protein kinase (MAPK) in LOX-1 KO mice treated with DOX than WT mice treated with DOX. In fact, NF-kappaB-dependent gene expressions of LOX-1 and vascular cell adhesion molecule-1 (VCAM-1) were suppressed in LOX-1 KO mice treated with DOX compared with WT mice treated with DOX. Therefore, histological analyses showed attenuation of leukocyte infiltration and cardiac fibrosis in LOX-1 KO mice compared with WT mice. Meanwhile, extracellular signal-regulated kinase MAPK (ERK) inactivation and decreased expression of sarcomeric proteins and related transcription factor GATA-4 in WT mice treated with DOX administration were not seen in LOX-1 KO mice treated with DOX administration and WT and LOX-1 KO mice treated with vehicle. Decreased expression of sarcometric proteins resulted in smaller diameters of cardiomyocytes in WT mice than in LOX-1 KO mice after DOX treatment. The expression of LOX-1 in cardiomyocytes was much more abundant than that in endothelial cells, fibroblasts and inflammatory cells. Endothelial cells, fibroblasts and inflammatory cells treated with DOX showed no elevated LOX-1 expression compared with those treated with vehicle. However, cardiomyocytes treated with DOX showed much more expression of LOX-1 than those treated with vehicle. Immunohistochemistry study also showed that LOX-1 expression was strongly elevated in cardiomyocytes in the heart tissue of mice treated with DOX in vivo. We conclude that LOX-1 in cardiomyocytes plays the most important roles in the pathology of DOX-induced cardiomyopathy. LOX-1 deletion altered the LOX-1 related signaling pathway, which led to improvements in cardiac function, myocardial inflammation, fibrosis and degenerative changes after DOX treatment. PMID- 27195773 TI - Peat soil bulk density important for estimation of peatland fire emissions. PMID- 27195771 TI - Functional Overexpression of Vomeronasal Receptors Using a Herpes Simplex Virus Type 1 (HSV-1)-Derived Amplicon. AB - In mice, social behaviors such as mating and aggression are mediated by pheromones and related chemosignals. The vomeronasal organ (VNO) detects olfactory information from other individuals by sensory neurons tuned to respond to specific chemical cues. Receptors expressed by vomeronasal neurons are implicated in selective detection of these cues. Nearly 400 receptor genes have been identified in the mouse VNO, but the tuning properties of individual receptors remain poorly understood, in part due to the lack of a robust heterologous expression system. Here we develop a herpes virus-based amplicon delivery system to overexpress three types of vomeronasal receptor genes and to characterize cell responses to their proposed ligands. Through Ca2+ imaging in native VNO cells we show that virus-induced overexpression of V1rj2, V2r1b or Fpr3 caused a pronounced increase of responsivity to sulfated steroids, MHC binding peptide or the synthetic hexapeptide W-peptide, respectively. Other related ligands were not recognized by infected individual neurons, indicating a high degree of selectivity by the overexpressed receptor. Removal of G-protein signaling eliminates Ca2+ responses, indicating that the endogenous second messenger system is essential for observing receptor activation. Our results provide a novel expression system for vomeronasal receptors that should be useful for understanding the molecular logic of VNO ligand detection. Functional expression of vomeronasal receptors and their deorphanization provides an essential requirement for deciphering the neural mechanisms controlling behavior. PMID- 27195772 TI - The Edinburgh Cognitive and Behavioural ALS Screen in a Chinese Amyotrophic Lateral Sclerosis Population. AB - OBJECTIVE: The existing screening batteries assessing multiple neuropsychological functions are not specific to amyotrophic lateral sclerosis (ALS) patients and are limited to their physical dysfunctions, whereas category cognitive tests are too time-consuming to assess all the domains. The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) was recently developed as a fast and easy cognitive screening tool specifically designed for patients. The purpose of the study was to validate the effectiveness of the Chinese version in Chinese ALS populations. METHODS: Eighty-four ALS patients and 84 age-, gender- and education-matched healthy controls were included in this cross-sectional study. All the participants took the ECAS, Mini-Mental State Examination (MMSE) and Frontal Assessment Battery (FAB). Primary caregivers of patients were interviewed for behavioural and psychiatric changes. RESULTS: Significant differences were noted in language (p = 0.01), fluency, executive function, ALS-specific functions, and ECAS total score (p<0.01) between ALS patients and controls. The cut-off value of the total ECAS score was 81.92. Cognitive impairment was observed in 35.71% of patients, and 27.38% exhibited behavioural abnormalities. The ECAS total score had a medium correlation with education year. Memory was more easily impaired in the lower education group, whereas verbal fluency and language function tended to be preserved in the higher education group. The average time of ECAS was only 18 minutes. CONCLUSION: The Chinese version of the ECAS is the first screening battery assessing multiple neuropsychological functions specially designed for the ALS population in China, which provides an effective and rapid tool to screen cognitive and behavioural impairments. PMID- 27195774 TI - Ferric carboxymaltose with or without erythropoietin in anemic patients with hip fracture: a randomized clinical trial. AB - BACKGROUND: The increasing incidence of osteoporotic hip fracture (HF) has raised the requirements of red blood cell (RBC) transfusions, whereas this scarce resource may cause morbidity and mortality. STUDY DESIGN AND METHODS: This study was a multicenter, randomized, double-blind, clinical trial that aimed to assess efficacy of ferric carboxymaltose (FCM) with or without erythropoietin (EPO) in reducing RBC transfusion in the perioperative period of HF. Participants (patients > 65 years admitted with HF and hemoglobin [Hb] levels of 90-120 g/L) were randomly assigned to receive a preoperative single dose of 1 g of FCM (short intravenous [IV] infusion over 15 min), plus 40,000 IU of subcutaneous EPO (EPOFE arm); versus 1 g of IV FCM plus subcutaneous placebo (FE arm); and versus IV and subcutaneous placebo (placebo arm). Primary endpoint was the percentage of patients who received RBC transfusion, and secondary endpoints were the number of RBC transfusions per patient, survival, hemoglobinemia, and health-related quality of life (HRQoL; by means of Short Form 36 Version 2 questionnaire). RESULTS: A total of 306 patients (85% women, mean age 83 +/- 6.5 years) were included. A total of 52, 51.5, and 54% of patients required RBC transfusion in the EPOFE, FE, and placebo arms, respectively, with no significant differences in the number of RBC transfusions per patient, survival, HRQoL, and adverse events among treatment groups. A significant increase in Hb levels was achieved at discharge (102 g/L vs. 97 g/L) and 60 days after discharge (125 g/L vs. 119 g/L) in the EPOFE arm with respect to placebo arm; in addition, a higher rate of patients recovered from anemia in the EPOFE arm with respect to the placebo arm (52% vs. 39%), 60 days after discharge. CONCLUSION: Preoperative treatment with FCM alone or in combination with EPO improved recovery from postoperative anemia, but did not reduce the needs of RBC transfusion in patients with HF. PMID- 27195775 TI - Correction: Topical HPMC/S-Nitrosoglutathione Solution Decreases Inflammation and Bone Resorption in Experimental Periodontal Disease in Rats. AB - [This corrects the article DOI: 10.1371/journal.pone.0153716.]. PMID- 27195777 TI - Genome-Wide Association Study of Absolute QRS Voltage Identifies Common Variants of TBX3 as Genetic Determinants of Left Ventricular Mass in a Healthy Japanese Population. AB - Left ventricular hypertrophy (LVH) represents a common final pathway leading to heart failure. We have searched for genetic determinants of left ventricular (LV) mass using values for absolute electrocardiographic QRS voltage in a healthy Japanese population. After adjusting for covariates, the corrected S and R wave voltages in leads V1 and V5 from 2,994 healthy volunteers in the Japan Pharmacogenomics Data Science Consortium (JPDSC) database were subjected to a genome-wide association study. Potential associations were validated by an in silico replication study using an independent Japanese population obtained from the Nagahama Prospective Genome Cohort for Comprehensive Human Bioscience. We identified a novel association between the lead V5, R wave voltage in Japanese individuals and SNP rs7301743[G], which maps near the gene encoding T-box transcription factor Tbx3. Meta-analysis of two independent Japanese datasets demonstrated a marginally significant association of SNP rs7301743 in TBX3|MED13L with a 0.071 mV (95% CI, 0.038-0.11 mV) shorter R wave amplitude in the V5 lead per minor allele copy (P = 7.635 x 10(-8)). The transcriptional repressor, TBX3, is proposed to suppress the development of working ventricular myocardium. Our findings suggest that genetic variation of Tbx3 is associated with LV mass in a healthy Japanese population. PMID- 27195776 TI - Bloodstream-To-Eye Infections Are Facilitated by Outer Blood-Retinal Barrier Dysfunction. AB - The blood-retinal barrier (BRB) functions to maintain the immune privilege of the eye, which is necessary for normal vision. The outer BRB is formed by tightly associated retinal pigment epithelial (RPE) cells which limit transport within the retinal environment, maintaining retinal function and viability. Retinal microvascular complications and RPE dysfunction resulting from diabetes and diabetic retinopathy cause permeability changes in the BRB that compromise barrier function. Diabetes is the major predisposing condition underlying endogenous bacterial endophthalmitis (EBE), a blinding intraocular infection resulting from bacterial invasion of the eye from the bloodstream. However, significant numbers of EBE cases occur in non-diabetics. In this work, we hypothesized that dysfunction of the outer BRB may be associated with EBE development. To disrupt the RPE component of the outer BRB in vivo, sodium iodate (NaIO3) was administered to C57BL/6J mice. NaIO3-treated and untreated mice were intravenously injected with 108 colony forming units (cfu) of Staphylococcus aureus or Klebsiella pneumoniae. At 4 and 6 days postinfection, EBE was observed in NaIO3-treated mice after infection with K. pneumoniae and S. aureus, although the incidence was higher following S. aureus infection. Invasion of the eye was observed in control mice following S. aureus infection, but not in control mice following K. pneumoniae infection. Immunohistochemistry and FITC-dextran conjugate transmigration assays of human RPE barriers after infection with an exoprotein-deficient agr/sar mutant of S. aureus suggested that S. aureus exoproteins may be required for the loss of the tight junction protein, ZO-1, and for permeability of this in vitro barrier. Our results support the clinical findings that for both pathogens, complications which result in BRB permeability increase the likelihood of bacterial transmigration from the bloodstream into the eye. For S. aureus, however, BRB permeability is not required for the development of EBE, but toxin production may facilitate EBE pathogenesis. PMID- 27195778 TI - Evaluation of a dysphagia screening system based on the Mann Assessment of Swallowing Ability for use in dependent older adults. AB - AIM: Dysphagia is common in dependent older adults. Thus, a method of evaluating eating and swallowing functions that can be used to diagnose and manage dysphagia in a simple and robust manner is required. In 2002, the Mann Assessment of Swallowing Ability (MASA) was introduced to identify dysphagia in acute-stage stroke patients. As the MASA enables easy screening, it might also be applicable to dependent older adults if appropriate MASA cut-off values and the most useful assessment items could be determined. In the present study, we attempted to determine suitable MASA cut-off values, and the most useful assessment items for predicting aspiration and pharyngeal retention in dependent older adults. METHODS: Using the MASA, we evaluated the eating and swallowing functions of 50 dependent older adults with dysphagia. All of the patients also underwent videoendoscopic-based swallowing evaluations to detect aspiration and pharyngeal retention. The participants' characteristics and the utility of each assessment item were compared between various groups. Using the patients' videoendoscopic findings as a reference, receiver operating characteristic curve analysis was carried out to determine appropriate cut-off values for predicting aspiration and pharyngeal retention in dependent older adults. RESULTS: The optimal MASA cut-off values for predicting aspiration and pharyngeal retention were 122 points and 151 points, respectively. A total of 17 of the 24 clinical items assessed by the MASA were found to be associated with aspiration in dependent older adults. CONCLUSIONS: The MASA is a useful screening tool for evaluating eating and swallowing functions in dependent older adults. Geriatr Gerontol Int 2017; 17: 561-567. PMID- 27195779 TI - Findings and Outcomes in a Prevaccination Cohort of Women Younger Than 25 Years Attending a Tertiary Colposcopy Service. AB - OBJECTIVE: To describe clinical presentation and treatment in women younger than 25 years referred to the Royal Women's Hospital colposcopy clinic, before implementation of the National Human Papillomavirus Vaccination Program. METHODS: Retrospective cohort analysis of women younger than 25 years referred to a tertiary hospital colposcopy clinic between 1998 and 2007. Clinical presentation and correlation between cervical cytology, biopsy, and histology at treatment was examined. RESULTS: Approximately 14,635 colposcopies were undertaken in 4104 women (median age, 22 years); 3051 had abnormal referral cytology, of whom, 23.8% had high-grade disease on punch biopsy. High-grade disease was found in 15.1% of those with possible low-grade or low-grade cytology (293/1932), 42.4% of those with possible high-grade or high-grade cytology (474/1119). Sensitivity and specificity of colposcopy for high-grade disease (high-grade epithelial abnormality, adenocarcinoma in situ, cervical cancer up to 2 years follow-up) was 60.0% and 82.3%, respectively. Thirty-nine percent (n = 1180) with abnormal cytology had treatment, of which, 66.6% was ablative. Histological CIN3+ was found in 53.8% of those with a previous high-grade punch biopsy (126/234) at excisional treatment, and 23.0% of those with a previous low-grade punch biopsy (20/87) (relative risk, 2.3 [CI, 1.6-3.5]). Four cancers were detected (0.1% of the total cohort, 0.5% of those with a high-grade biopsy, and 1.7% of those with a high-grade biopsy who underwent excisional treatment.) CONCLUSIONS: Before vaccination, young women experienced a high real-time burden of high-grade disease and high rates of intervention. These baseline data contribute to monitoring of HPV vaccination and revised cervical screening strategies. PMID- 27195780 TI - Regorafenib-Associated Vulvar Psoriasiform Skin Reaction: Case of the Month from the ISSVD Case Consultation Committee. PMID- 27195781 TI - Vulvar Ulcers Leading to Cutaneous Perforation in an Immunocompetent Teenager: Expression of Cytomegalovirus Infection. PMID- 27195783 TI - Quantitative Contribution of IL2Rgamma to the Dynamic Formation of IL2-IL2R Complexes. AB - Interleukin-2 (IL2) is a growth factor for several immune cells and its function depends on its binding to IL2Rs in the cell membrane. The most accepted model for the assembling of IL2-IL2R complexes in the cell membrane is the Affinity Conversion Model (ACM). This model postulates that IL2R receptor association is sequential and dependent on ligand binding. Most likely free IL2 binds first to IL2Ralpha, and then this complex binds to IL2Rbeta, and finally to IL2Rgamma (gammac). However, in previous mathematical models representing this process, the binding of gammac has not been taken into account. In this work, the quantitative contribution of the number of IL2Rgamma chain to the IL2-IL2R apparent binding affinity and signaling is studied. A mathematical model of the affinity conversion process including the gamma chain in the dynamic, has been formulated. The model was calibrated by fitting it to experimental data, specifically, Scatchard plots obtained using human cell lines. This paper demonstrates how the model correctly explains available experimental observations. It was estimated, for the first time, the value of the kinetic coefficients of IL2-IL2R complexes interaction in the cell membrane. Moreover, the number of IL2R components in different cell lines was also estimated. It was obtained a variable distribution in the number of IL2R components depending on the cell type and the activation state. Of most significance, the study predicts that not only the number of IL2Ralpha and IL2Rbeta, but also the number of gammac determine the capacity of the cell to capture and retain IL2 in signalling complexes. Moreover, it is also showed that different cells might use different pathways to bind IL2 as consequence of its IL2R components distribution in the membrane. PMID- 27195782 TI - Additive Expression of Consolidated Memory through Drosophila Mushroom Body Subsets. AB - Associative olfactory memory in Drosophila has two components called labile anesthesia-sensitive memory and consolidated anesthesia-resistant memory (ARM). Mushroom body (MB) is a brain region critical for the olfactory memory and comprised of 2000 neurons that can be classified into alphabeta, alpha'beta', and gamma neurons. Previously we demonstrated that two parallel pathways mediated ARM consolidation: the serotonergic dorsal paired medial (DPM)-alphabeta neurons and the octopaminergic anterior paired lateral (APL)-alpha'beta' neurons. This finding prompted us to ask how this composite ARM is retrieved. Here, we showed that blocking the output of alphabeta neurons and that of alpha'beta' neurons each impaired ARM retrieval, and blocking both simultaneously had an additive effect. Knockdown of radish and octbeta2R in alphabeta and alpha'beta' neurons, respectively, impaired ARM. A combinatorial assay of radish mutant background rsh1 and neurotransmission blockade confirmed that ARM retrieved from alpha'beta' neuron output is independent of radish. We identified MBON-beta2beta'2a and MBON beta'2mp as the MB output neurons downstream of alphabeta and alpha'beta' neurons, respectively, whose glutamatergic transmissions also additively contribute to ARM retrieval. Finally, we showed that alpha'beta' neurons could be functionally subdivided into alpha'beta'm neurons required for ARM retrieval, and alpha'beta'ap neurons required for ARM consolidation. Our work demonstrated that two parallel neural pathways mediating ARM consolidation in Drosophila MB additively contribute to ARM expression during retrieval. PMID- 27195784 TI - Differences in quality of life of women and men with drug-resistant epilepsy in Poland. AB - PURPOSE: The aim of the study was to assess the differences in health-related quality of life in groups of men and women suffering with drug-resistant epilepsy and to determine which factors influence quality of life. METHODS: The examined group consisted of 64 subjects with drug-resistant epilepsy - 31 men and 33 women. The mean duration of epilepsy was 17.56+/-8.92 and 19+/-9.56years, respectively. The following diagnostic tools were used: QOLIE-31-P, Wechsler Adult Intelligence Scale - Revised (WAIS-R (PL)), and Hamilton Rating Scale for Depression (HRSD). RESULTS: Scores in QOLIE-31-P did not differ significantly between groups of men and women with drug-resistant epilepsy; however, a more detailed analysis revealed certain disparities. Multiple regression analyses indicated that some distinct factors were associated with quality of life in each sex. In the group of women, there were no significant predictors of their quality of life. Among the group of men, depression intensity was the only statistically significant QoL predictor, explaining 16% of the variance (adjusted R(2)=0.16, F(6, 24)=19.7, p<0.01). Moreover, patients with depression had lowered scores in the Emotional Well-Being and Energy/Fatigue subscales, regardless of the sex. CONCLUSION: The study revealed that, despite similar scores in QOLIE-31-P, specific factors may differentially affect the quality of life of men and women with drug-resistant epilepsy in Poland. Nevertheless, replication of these results with a larger number of participants is needed for a more definitive conclusion. PMID- 27195785 TI - Coprolalia as a manifestation of epileptic seizures. AB - OBJECTIVE: The aim of this study was to investigate the lateralizing and localizing value of ictal coprolalia and brain areas involved in its production. METHODS: A retrospective search for patients manifesting ictal coprolalia was conducted in our EMU database. Continuous video-EEG recordings were reviewed, and EEG activity before and during coprolalia was analyzed using independent component analysis (ICA) technique and was compared to the seizures without coprolalia among the same patients. RESULTS: Nine patients were evaluated (five women), eight with intracranial video-EEG recordings (icVEEG). Four had frontal or temporal lesions, and five had normal MRIs. Six patients showed impairment in the language functions and five in the frontal executive tasks. Two hundred six seizures were reviewed (60.7% from icVEEG). Ictal coprolalia occurred in 46.6% of them, always associated with limbic auras or automatisms. They arose from the nondominant hemisphere in five patients, dominant hemisphere in three, and independently from the right and left hippocampus-parahippocampus in one. Electroencephalographic activity always involved orbitofrontal and/or mesial temporal regions of the nondominant hemisphere when coprolalia occurred. Independent component analysis of 31 seizures in seven patients showed a higher number of independent components in the nondominant hippocampus-parahippocampus before and during coprolalia and in the dominant lateral temporal region in those seizures without coprolalia (p=0.009). Five patients underwent surgery, and all five had an ILAE class 1 outcome. SIGNIFICANCE: Ictal coprolalia occurs in both males and females with temporal or orbitofrontal epilepsy and has a limited lateralizing value to the nondominant hemisphere but can be triggered by seizures from either hemisphere. It involves activation of the paralimbic temporal orbitofrontal network. PMID- 27195786 TI - Impact of an Early Invasive Strategy versus Conservative Strategy for Unstable Angina and Non-ST Elevation Acute Coronary Syndrome in Patients with Chronic Kidney Disease: A Systematic Review. AB - BACKGROUND: Clinical practice guidelines support an early invasive approach after NSTE-ACS in patients with chronic kidney disease (CKD). There is no direct randomised controlled trial evidence in the CKD population, and whether the benefit of an early invasive approach is maintained across the spectrum of severity of CKD remains controversial. METHODS: We conducted a systematic review to evaluate the association between an early invasive approach and all-cause mortality in patients with CKD. We searched MEDLINE and EMBASE (1990-May 2015) and article reference lists. Data describing study design, participants, invasive management strategies, renal function, all-cause mortality and risk of bias were extracted. RESULTS: 3,861 potentially relevant studies were identified. Ten studies, representing data on 147,908 individuals with NSTE-ACS met the inclusion criteria. Qualitative heterogeneity in the definitions of early invasive approach, comparison groups and renal dysfunction existed. Meta-analysis of the RCT derived and observational data were generally supportive of an early invasive approach in CKD (RR0.76 (95% CI 0.49-1.17) and RR0.50 (95%CI 0.42-0.59) respectively). Meta-analysis of the observational studies demonstrated a large degree of heterogeneity (I2 79%) driven in part by study size and heterogeneity across various kidney function levels. CONCLUSIONS: The observational data support that an early invasive approach after NSTE-ACS confers a survival benefit in those with early-moderate CKD. Local opportunities for quality improvement should be sought. Those with severe CKD and the dialysis population are high risk and under-studied. Novel and inclusive approaches for CKD and dialysis patients in cardiovascular clinical trials are needed. PMID- 27195787 TI - Collaborative Filtering Recommendation on Users' Interest Sequences. AB - As an important factor for improving recommendations, time information has been introduced to model users' dynamic preferences in many papers. However, the sequence of users' behaviour is rarely studied in recommender systems. Due to the users' unique behavior evolution patterns and personalized interest transitions among items, users' similarity in sequential dimension should be introduced to further distinguish users' preferences and interests. In this paper, we propose a new collaborative filtering recommendation method based on users' interest sequences (IS) that rank users' ratings or other online behaviors according to the timestamps when they occurred. This method extracts the semantics hidden in the interest sequences by the length of users' longest common sub-IS (LCSIS) and the count of users' total common sub-IS (ACSIS). Then, these semantics are utilized to obtain users' IS-based similarities and, further, to refine the similarities acquired from traditional collaborative filtering approaches. With these updated similarities, transition characteristics and dynamic evolution patterns of users' preferences are considered. Our new proposed method was compared with state-of-the-art time-aware collaborative filtering algorithms on datasets MovieLens, Flixster and Ciao. The experimental results validate that the proposed recommendation method is effective and outperforms several existing algorithms in the accuracy of rating prediction. PMID- 27195788 TI - When mental fatigue maybe characterized by Event Related Potential (P300) during virtual wheelchair navigation. AB - The goal of this study is to investigate the influence of mental fatigue on the event related potential P300 features (maximum pick, minimum amplitude, latency and period) during virtual wheelchair navigation. For this purpose, an experimental environment was set up based on customizable environmental parameters (luminosity, number of obstacles and obstacles velocities). A correlation study between P300 and fatigue ratings was conducted. Finally, the best correlated features supplied three classification algorithms which are MLP (Multi Layer Perceptron), Linear Discriminate Analysis and Support Vector Machine. The results showed that the maximum feature over visual and temporal regions as well as period feature over frontal, fronto-central and visual regions were correlated with mental fatigue levels. In the other hand, minimum amplitude and latency features didn't show any correlation. Among classification techniques, MLP showed the best performance although the differences between classification techniques are minimal. Those findings can help us in order to design suitable mental fatigue based wheelchair control. PMID- 27195789 TI - Standardized Loads Acting in Hip Implants. AB - With the increasing success of hip joint replacements, the average age of patients has decreased, patients have become more active and their expectations of the implant durability have risen. Thus, pre-clinical endurance tests on hip implants require defining realistic in vivo loads from younger and more active patients. These loads require simplifications to be applicable for simulator tests and numerical analyses. Here, the contact forces in the joint were measured with instrumented hip implants in ten subjects during nine of the most physically demanding and frequent activities of daily living. Typical levels and directions of average and high joint loads were extracted from the intra- and inter individually widely varying individual data. These data can also be used to analyse bone remodelling at the implant-bone interface, evaluate tissue straining in finite element studies or validate analytical loading predictions, among other uses. The current ISO standards for endurance tests of implant stems and necks are based on historic analytical data from the 1970s. Comparisons of these test forces with in vivo loads unveiled that their unidirectional orientations deviate from the time-dependent in vivo directions during walking and most other activities. The ISO force for testing the stem is substantially too low while the ISO force for the neck better matches typical in vivo magnitudes. Because the magnitudes and orientations of peak forces substantially vary among the activities, load scenarios that reflect a collection of time-dependent high forces should be applied rather than using unidirectional forces. Based on data from ten patients, proposals for the most demanding activities, the time courses of the contact forces and the required cycle numbers for testing are given here. Friction moments in the joint were measured in addition to the contact forces. The moment data were also standardized and can be applied to wear tests of the implant. It was shown that friction only very slightly influences the stresses in the implant neck and shaft. PMID- 27195790 TI - Chemical and Antimicrobial Profiling of Propolis from Different Regions within Libya. AB - Extracts from twelve samples of propolis collected from different regions of Libya were tested for their activity against Trypanosoma brucei, Leishmania donovani, Plasmodium falciparum, Crithidia fasciculata and Mycobacterium marinum and the cytotoxicity of the extracts was tested against mammalian cells. All the extracts were active to some degree against all of the protozoa and the mycobacterium, exhibiting a range of EC50 values between 1.65 and 53.6 MUg/ml. The toxicity against mammalian cell lines was only moderate; the most active extract against the protozoan species, P2, displayed an IC50 value of 53.2 MUg/ml. The extracts were profiled by using liquid chromatography coupled to high resolution mass spectrometry. The data sets were extracted using m/z Mine and the accurate masses of the features extracted were searched against the Dictionary of Natural Products (DNP). A principal component analysis (PCA) model was constructed which, in combination with hierarchical cluster analysis (HCA), divided the samples into five groups. The outlying groups had different sets of dominant compounds in the extracts, which could be characterised by their elemental composition. Orthogonal partial least squares (OPLS) analysis was used to link the activity of each extract against the different micro-organisms to particular components in the extracts. PMID- 27195791 TI - East Coast Fever Caused by Theileria parva Is Characterized by Macrophage Activation Associated with Vasculitis and Respiratory Failure. AB - Respiratory failure and death in East Coast Fever (ECF), a clinical syndrome of African cattle caused by the apicomplexan parasite Theileria parva, has historically been attributed to pulmonary infiltration by infected lymphocytes. However, immunohistochemical staining of tissue from T. parva infected cattle revealed large numbers of CD3- and CD20-negative intralesional mononuclear cells. Due to this finding, we hypothesized that macrophages play an important role in Theileria parva disease pathogenesis. Data presented here demonstrates that terminal ECF in both Holstein and Boran cattle is largely due to multisystemic histiocytic responses and resultant tissue damage. Furthermore, the combination of these histologic changes with the clinical findings, including lymphadenopathy, prolonged pyrexia, multi-lineage leukopenia, and thrombocytopenia is consistent with macrophage activation syndrome. All animals that succumbed to infection exhibited lymphohistiocytic vasculitis of small to medium caliber blood and lymphatic vessels. In pulmonary, lymphoid, splenic and hepatic tissues from Holstein cattle, the majority of intralesional macrophages were positive for CD163, and often expressed large amounts of IL-17. These data define a terminal ECF pathogenesis in which parasite-driven lymphoproliferation leads to secondary systemic macrophage activation syndrome, mononuclear vasculitis, pulmonary edema, respiratory failure and death. The accompanying macrophage phenotype defined by CD163 and IL-17 is presented in the context of this pathogenesis. PMID- 27195793 TI - The Preventability of Cancer: Stacking the Deck. PMID- 27195794 TI - Japanese care workers' perception of dementia-related physically and psychologically aggressive behaviour symptoms. AB - AIM: The purpose of this study was to explore Japanese care workers' attributions, beliefs and cultural explanations of physically and psychologically aggressive behaviour symptoms. BACKGROUND: Physically and psychologically aggressive behaviour symptoms by older people with dementia have been associated with occupational stress among care workers in the United States and other Western countries and may contribute to staff turnover. However, few studies related to this issue have been conducted in Japan, where care worker reaction to physically and psychologically aggressive behaviour symptoms might be different because of cultural and customary differences in how care is provided for older people. METHOD: This study reports on the results of three open-ended questions that were part of a larger study that explored Japanese care workers' experiences with aggressive behaviour symptoms in persons with dementia. Convenience sampling was used to recruit 137 care workers in 10 nursing homes in the northern and western areas of Japan. The answers to the open-ended questions were analysed using a content analysis. FINDINGS: Most of the participants indicated that they believed that physically and psychologically aggressive behaviour symptoms came from residents' stress from dementia. Approximately, one-fourth of the participants responded that Japanese values such as chu (loyalty) and joge (hierarchy) influenced their work with residents with physically and psychologically aggressive behaviour symptoms. Seventeen participants (12%) commented either that they respected older people or that they respected older people as persons who had had many experiences in life. Interestingly, 43 responses (41.0%) indicated that physically and psychologically aggressive behaviour symptoms influenced quality of care positively, while, not surprisingly, about 30 responses indicated that those behaviour symptoms influenced quality of care negatively. IMPLICATIONS FOR PRACTICE: Findings from this study indicate that the training and education needs to focus on understand and preventing the effects of stress for individuals living with dementia to reduce aggressive incidents and increase recruitment and retention of care workers. PMID- 27195792 TI - Untangling the relatedness among correlations, part I: Nonparametric approaches to inter-subject correlation analysis at the group level. AB - FMRI data acquisition under naturalistic and continuous stimuli (e.g., watching a video or listening to music) has become popular recently due to the fact that it entails less manipulation and more realistic/complex contexts involved in the task, compared to the conventional task-based experimental designs. The synchronization or response similarities among subjects are typically measured through inter-subject correlation (ISC) between any pair of subjects. At the group level, summarizing the collection of ISC values is complicated by their intercorrelations, which necessarily lead to the violation of independence assumed in typical parametric approaches such as Student's t-test. Nonparametric methods, such as bootstrapping and permutation testing, have previously been adopted for testing purposes by resampling the time series of each subject, but the quantitative validity of these specific approaches in terms of controllability of false positive rate (FPR) has never been explored before. Here we survey the methods of ISC group analysis that have been employed in the literature, and discuss the issues involved in those methods. We then propose less computationally intensive nonparametric methods that can be performed at the group level (for both one- and two-sample analyses), as compared to the popular method of circularly shifting the EPI time series at the individual level. As part of the new approaches, subject-wise (SW) resampling is adopted instead of element-wise (EW) resampling, so that exchangeability and independence assumptions are satisfied, and the patterned correlation structure among the ISC values can be more accurately captured. We examine the FPR controllability and power achievement of all the methods through simulations, as well as their performance when applied to a real experimental dataset. PMID- 27195795 TI - Multiplex Real-Time qPCR Assay for Simultaneous and Sensitive Detection of Phytoplasmas in Sesame Plants and Insect Vectors. AB - Phyllody, a destructive and economically important disease worldwide caused by phytoplasma infections, is characterized by the abnormal development of floral structures into stunted leafy parts and contributes to serious losses in crop plants, including sesame (Sesamum indicum L.). Accurate identification, differentiation, and quantification of phyllody-causing phytoplasmas are essential for effective management of this plant disease and for selection of resistant sesame varieties. In this study, a diagnostic multiplex qPCR assay was developed using TaqMan(r) chemistry based on detection of the 16S ribosomal RNA gene of phytoplasmas and the 18S ribosomal gene of sesame. Phytoplasma and sesame specific primers and probes labeled with different fluorescent dyes were used for simultaneous amplification of 16SrII and 16SrIX phytoplasmas in a single tube. The multiplex real-time qPCR assay allowed accurate detection, differentiation, and quantification of 16SrII and 16SrIX groups in 109 sesame plant and 92 insect vector samples tested. The assay was found to have a detection sensitivity of 1.8 x 10(2) and 1.6 x 10(2) DNA copies for absolute quantification of 16SrII and 16SrIX group phytoplasmas, respectively. Relative quantification was effective and reliable for determination of phyllody phytoplasma DNA amounts normalized to sesame DNA in infected plant tissues. The development of this qPCR assay provides a method for the rapid measurement of infection loads to identify resistance levels of sesame genotypes against phyllody phytoplasma disease. PMID- 27195798 TI - Solution Processed PEDOT Analogues in Electrochemical Supercapacitors. AB - We have designed fully soluble ProDOTx-EDOTy copolymers that are electrochemically equivalent to electropolymerized PEDOT without using any surfactants or dispersants. We show that these copolymers can be incorporated as active layers in solution processed thin film supercapacitors to demonstrate capacitance, stability, and voltage similar to the values of those that use electrodeposited PEDOT as the active material with the added advantage of the possibility for large scale, high-throughput processing. These Type I supercapacitors provide exceptional cell voltages (up to 1.6 V), highly symmetrical charge/discharge behavior, promising long-term stability exceeding 50 000 charge/discharge cycles, as well as energy (4-18 Wh/kg) and power densities (0.8-3.3 kW/kg) that are comparable to those of electrochemically synthesized analogues. PMID- 27195796 TI - Characterization of a DNA Adenine Methyltransferase Gene of Borrelia hermsii and Its Dispensability for Murine Infection and Persistence. AB - DNA methyltransferases have been implicated in the regulation of virulence genes in a number of pathogens. Relapsing fever Borrelia species harbor a conserved, putative DNA methyltransferase gene on their chromosome, while no such ortholog can be found in the annotated genome of the Lyme disease agent, Borrelia burgdorferi. In the relapsing fever species Borrelia hermsii, the locus bh0463A encodes this putative DNA adenine methyltransferase (dam). To verify the function of the BH0463A protein product as a Dam, the gene was cloned into a Dam-deficient strain of Escherichia coli. Restriction fragment analysis subsequently demonstrated that complementation of this E. coli mutant with bh0463A restored adenine methylation, verifying bh0463A as a Dam. The requirement of bh0463A for B. hermsii viability, infectivity, and persistence was then investigated by genetically disrupting the gene. The dam- mutant was capable of infecting immunocompetent mice, and the mean level of spirochetemia in immunocompetent mice was not significantly different from wild type B. hermsii. Collectively, the data indicate that dam is dispensable for B. hermsii viability, infectivity, and persistence. PMID- 27195799 TI - An Efficient Acoustic Density Estimation Method with Human Detectors Applied to Gibbons in Cambodia. AB - Some animal species are hard to see but easy to hear. Standard visual methods for estimating population density for such species are often ineffective or inefficient, but methods based on passive acoustics show more promise. We develop spatially explicit capture-recapture (SECR) methods for territorial vocalising species, in which humans act as an acoustic detector array. We use SECR and estimated bearing data from a single-occasion acoustic survey of a gibbon population in northeastern Cambodia to estimate the density of calling groups. The properties of the estimator are assessed using a simulation study, in which a variety of survey designs are also investigated. We then present a new form of the SECR likelihood for multi-occasion data which accounts for the stochastic availability of animals. In the context of gibbon surveys this allows model-based estimation of the proportion of groups that produce territorial vocalisations on a given day, thereby enabling the density of groups, instead of the density of calling groups, to be estimated. We illustrate the performance of this new estimator by simulation. We show that it is possible to estimate density reliably from human acoustic detections of visually cryptic species using SECR methods. For gibbon surveys we also show that incorporating observers' estimates of bearings to detected groups substantially improves estimator performance. Using the new form of the SECR likelihood we demonstrate that estimates of availability, in addition to population density and detection function parameters, can be obtained from multi-occasion data, and that the detection function parameters are not confounded with the availability parameter. This acoustic SECR method provides a means of obtaining reliable density estimates for territorial vocalising species. It is also efficient in terms of data requirements since since it only requires routine survey data. We anticipate that the low-tech field requirements will make this method an attractive option in many situations where populations can be surveyed acoustically by humans. PMID- 27195797 TI - Hepatic Safety of Rilpivirine/Emtricitabine/Tenofovir Disoproxil Fumarate Fixed Dose Single-Tablet Regimen in HIV-Infected Patients with Active Hepatitis C Virus Infection: The hEPAtic Study. AB - OBJECTIVES: The aim of this study was to evaluate the frequency of transaminase elevations (TE) and total bilirubin elevations (TBE) during the first year of therapy with a single tablet regimen including RPV/FTC/TDF (EPA) in HIV/hepatitis C virus (HCV)-coinfected subjects in clinical practice. METHODS: In a retrospective analysis, HIV/HCV-coinfected subjects who started EPA at 17 centres throughout Spain were included as cases. Subjects who started an antiretroviral therapy (ART) other than EPA during the study period at the same hospitals were randomly selected as controls in a 1:2 ratio. Primary outcome variables were grade (G) 3-4 TE and G4 TBE. RESULTS: Of the 519 subjects included, 173 individuals started EPA. Nine (5.2%) subjects of the EPA group and 49 (14.2%) controls were naive to ART. The median (Q1-Q3) follow-up was 11.2 (9.7-13.9) months. TE was observed in 2 [1.2%; 95% confidence interval (CI): 0.14%-4.1%] subjects receiving EPA and 11 (3.2%; 95%CI: 1.6%-5.6%) controls (p = 0.136), all events were G3. No patient discontinued ART due to TE. One (0.6%; 95%CI: 0.01% 3.1%) subject on EPA and 8 (2.3%; 95%CI: 1%-4.5%) subjects in the control group developed TBE (p = 0.141), without developing any other hepatic event during follow-up. Three (2.3%) subjects with cirrhosis versus 10 (3.1%) without cirrhosis showed G3-4 TE (p = 0.451). CONCLUSION: The frequency of severe liver toxicity in HIV/HCV-coinfected subjects receiving EPA under real-life conditions is very low, TE were generally mild and did not lead to drug discontinuation. All these data suggest that EPA can be safely used in this particular subpopulation. PMID- 27195801 TI - Correction: Pharmacological and Genetic Modulation of REV-ERB Activity and Expression Affects Orexigenic Gene Expression. AB - [This corrects the article DOI: 10.1371/journal.pone.0151014.]. PMID- 27195802 TI - Validating self-reporting of hearing-related symptoms against pure-tone audiometry, otoacoustic emission, and speech audiometry. AB - OBJECTIVE: To validate self-reported hearing-related symptoms among personnel exposed to moderately high occupational noise levels at an obstetrics clinic. DESIGN: Sensitivity, specificity, and predictive values were calculated for questionnaire items assessing hearing loss, tinnitus, sound sensitivity, poor hearing, difficulty perceiving speech, and sound-induced auditory fatigue. Hearing disorder was diagnosed by pure-tone audiometry, distortion product otoacoustic emissions, and HINT (Hearing In Noise Test). STUDY SAMPLE: Fifty-five female obstetrics personnel aged 22-63 participated; including 26 subjects reporting hearing loss, poor hearing, tinnitus, or sound sensitivity, and 29 randomly selected subjects who did not report these symptoms. RESULTS: The questionnaire item assessing sound-induced auditory fatigue had the best combination of sensitivity >=85% (95% CIs 56 to 100%) and specificity >=70% (95% CIs 55 to 84%) for hearing disorder diagnosed by audiometry or otoacoustic emission. Of those reporting sound-induced auditory fatigue 71% were predicted to have disorder diagnosed by otoacoustic emission. Participants reporting any hearing-related symptom had slightly worse measured hearing. CONCLUSIONS: We suggest including sound-induced auditory fatigue in questionnaires for identification of hearing disorder among healthcare personnel, though larger studies are warranted for precise estimates of diagnostic performance. Also, more specific and accurate hearing tests are needed to diagnose mild hearing disorder. PMID- 27195803 TI - Novel Convenient Synthesis of (10)B-Enriched Sodium Borohydride. AB - A convenient and efficient synthesis of (10)B-enriched sodium borohydride [Na(10)BH4] from commercially available (10)B-enriched boric acid [(10)B(OH)3] is described. The reaction sequence (10)B(OH)3 -> (10)B(On-Bu)3 -> (10)BH3.Et3N -> Na(10)BH4 afforded the product in 60-80% yield. The reaction was successfully scaled to hundreds of gram per run. PMID- 27195800 TI - Identifying Risk Factors for Recent HIV Infection in Kenya Using a Recent Infection Testing Algorithm: Results from a Nationally Representative Population Based Survey. AB - INTRODUCTION: A recent infection testing algorithm (RITA) that can distinguish recent from long-standing HIV infection can be applied to nationally representative population-based surveys to characterize and identify risk factors for recent infection in a country. MATERIALS AND METHODS: We applied a RITA using the Limiting Antigen Avidity Enzyme Immunoassay (LAg) on stored HIV-positive samples from the 2007 Kenya AIDS Indicator Survey. The case definition for recent infection included testing recent on LAg and having no evidence of antiretroviral therapy use. Multivariate analysis was conducted to determine factors associated with recent and long-standing infection compared to HIV-uninfected persons. All estimates were weighted to adjust for sampling probability and nonresponse. RESULTS: Of 1,025 HIV-antibody-positive specimens, 64 (6.2%) met the case definition for recent infection and 961 (93.8%) met the case definition for long standing infection. Compared to HIV-uninfected individuals, factors associated with higher adjusted odds of recent infection were living in Nairobi (adjusted odds ratio [AOR] 11.37; confidence interval [CI] 2.64-48.87) and Nyanza (AOR 4.55; CI 1.39-14.89) provinces compared to Western province; being widowed (AOR 8.04; CI 1.42-45.50) or currently married (AOR 6.42; CI 1.55-26.58) compared to being never married; having had >= 2 sexual partners in the last year (AOR 2.86; CI 1.51-5.41); not using a condom at last sex in the past year (AOR 1.61; CI 1.34 1.93); reporting a sexually transmitted infection (STI) diagnosis or symptoms of STI in the past year (AOR 1.97; CI 1.05-8.37); and being aged <30 years with: 1) HSV-2 infection (AOR 8.84; CI 2.62-29.85), 2) male genital ulcer disease (AOR 8.70; CI 2.36-32.08), or 3) lack of male circumcision (AOR 17.83; CI 2.19 144.90). Compared to HIV-uninfected persons, factors associated with higher adjusted odds of long-standing infection included living in Coast (AOR 1.55; CI 1.04-2.32) and Nyanza (AOR 2.33; CI 1.67-3.25) provinces compared to Western province; being separated/divorced (AOR 1.87; CI 1.16-3.01) or widowed (AOR 2.83; CI 1.78-4.45) compared to being never married; having ever used a condom (AOR 1.61; CI 1.34-1.93); and having a STI diagnosis or symptoms of STI in the past year (AOR 1.89; CI 1.20-2.97). Factors associated with lower adjusted odds of long-standing infection included using a condom at last sex in the past year (AOR 0.47; CI 0.36-0.61), having no HSV2-infection at aged <30 years (AOR 0.38; CI 0.20-0.75) or being an uncircumcised male aged <30 years (AOR 0.30; CI 0.15 0.61). CONCLUSION: We identified factors associated with increased risk of recent and longstanding HIV infection using a RITA applied to blood specimens collected in a nationally representative survey. Though some false-recent cases may have been present in our sample, the correlates of recent infection identified were epidemiologically and biologically plausible. These methods can be used as a model for other countries with similar epidemics to inform targeted combination prevention strategies aimed to drastically decrease new infections in the population. PMID- 27195804 TI - Correction: Temperature Stress Mediates Decanalization and Dominance of Gene Expression in Drosophila melanogaster. AB - [This corrects the article DOI: 10.1371/journal.pgen.1004883.]. PMID- 27195805 TI - A Novel Reporter Rat Strain That Conditionally Expresses the Bright Red Fluorescent Protein tdTomato. AB - Despite the strength of the Cre/loxP recombination system in animal models, its application in rats trails that in mice because of the lack of relevant reporter strains. Here, we generated a floxed STOP tdTomato rat that conditionally expresses a red fluorescent protein variant (tdTomato) in the presence of exogenous Cre recombinase. The tdTomato signal vividly visualizes neurons including their projection fibers and spines without any histological enhancement. In addition, a transgenic rat line (FLAME) that ubiquitously expresses tdTomato was successfully established by injecting intracytoplasmic Cre mRNA into fertilized ova. Our rat reporter system will facilitate connectome studies as well as the visualization of the fine structures of genetically identified cells for long periods both in vivo and ex vivo. Furthermore, FLAME is an ideal model for organ transplantation research owing to improved traceability of cells/tissues. PMID- 27195806 TI - How Health Professionals Conceptualize and Represent Placebo Treatment in Clinical Trials and How Their Patients Understand It: Impact on Validity of Informed Consent. AB - CONTEXT: Previous studies suggested that many patients, who have given their informed consent to participate in randomized controlled trials (RCT), have somewhat limited understanding of what a placebo treatment is. We hypothesized that the relationship between patients and their health professionals plays a central role in this understanding. METHODS: We interviewed 12 patients included in RCTs (nine suffering from Parkinson's disease and three from Huntington's disease) and 18 health professionals involved with RCTs (eight principal investigators, four associated physicians and six clinical research associates). Semi-structured interviews were conducted after the RCTs had ended but before the treatment allocation was revealed. RESULTS: Only two patients clearly understood the aim of placebo-controlled RCTs. Only one principal investigator said she asks all her patients whether they agree to participate in RCTs. The seven others said they only ask patients who seem more likely to be compliant. Their selection criteria included docility and personality traits associated in other studies with enhanced placebo responses. According to 13 of the 18 health professionals, their relationship with patients may influence the amplitude of the placebo response. All but one clinical research associates added that the placebo response could result from a "maternal" type of care. All principal investigators said they have a strong influence on their patient's decision to participate. Finally, when interviewees were asked to narrate a memory of a medically unexplained healing, in eight of 11 physicians' narratives the beneficiary was a child while in 10 of 12 patients' narratives it was an adult. CONCLUSION: Our observations suggest that the interrelationship between health professionals and patients involved in RCTs could be compared to that between parents and children. Therefore, adherence to formal rules regarding informed consent does not ensure a balanced relationship between patients and health professionals. PMID- 27195807 TI - Antioxidant Potential of Vespa affinis L., a Traditional Edible Insect Species of North East India. AB - INTRODUCTION: Elevated oxidative stress plays an important role in the pathogenesis of health disorders, like arthritis. Traditionally, Vespa affinis L., a common edible insect among many tribes in North-East India, is believed to have a beneficial role in extenuating health disorders, such as arthritis. The present study investigated the molecular mechanism underlying medicinal benefit of the Aqueous Extract of Vespa affinis L. (AEVA) against oxidative stress pathophysiology. METHODS: The free radical scavenging activities of AEVA were examined against DPPH, hydroxyl, and superoxide radicals and the effect on the activities of antioxidant enzyme (GST and CAT) was determined using both recombinant proteins and human plasma. The antioxidant potential of AEVA was again investigated using THP-1 monocytes. RESULTS: AEVA possesses a significant free radical scavenging activity as evident from the DPPH, superoxide, and hydroxyl radical scavenging assay. Incubation of AEVA (2.5, 5, 7.5, and 10 MUg/MUL) with the recombinant antioxidant enzymes, rGST and rCAT significantly increased the enzyme activities compared to those observed in corresponding enzyme alone or AEVA itself. AEVA supplementation (5, 7.5, and 10 MUg/MUL) also stimulates the activities of GST and CAT when incubated with human plasma. A cell culture study also confirmed the beneficial role of AEVA (0.8 and 1.2 MUg/MUL) which enhances the activities of GST and CAT, and also reduces the intercellular ROS production in monocytes treated with or without H2O2 and the effects are at par with what is observed in N-acetyl cysteine-treated cells. CONCLUSION: The antioxidant potential of the aqueous extract of Vespa affinis L. may mediate its therapeutic activities in oxidative stress-associated health disorders. PMID- 27195808 TI - Areas of Agreement and Disagreement Regarding Ponderosa Pine and Mixed Conifer Forest Fire Regimes: A Dialogue with Stevens et al. AB - In a recent PLOS ONE paper, we conducted an evidence-based analysis of current versus historical fire regimes and concluded that traditionally defined reference conditions of low-severity fire regimes for ponderosa pine (Pinus ponderosa) and mixed-conifer forests were incomplete, missing considerable variability in forest structure and fire regimes. Stevens et al. (this issue) agree that high-severity fire was a component of these forests, but disagree that one of the several sources of evidence, stand age from a large number of forest inventory and analysis (FIA) plots across the western USA, support our findings that severe fire played more than a minor role ecologically in these forests. Here we highlight areas of agreement and disagreement about past fire, and analyze the methods Stevens et al. used to assess the FIA stand-age data. We found a major problem with a calculation they used to conclude that the FIA data were not useful for evaluating fire regimes. Their calculation, as well as a narrowing of the definition of high-severity fire from the one we used, leads to a large underestimate of conditions consistent with historical high-severity fire. The FIA stand age data do have limitations but they are consistent with other landscape-inference data sources in supporting a broader paradigm about historical variability of fire in ponderosa and mixed-conifer forests than had been traditionally recognized, as described in our previous PLOS paper. PMID- 27195809 TI - Interactive training improves workplace climate, knowledge, and support towards domestic violence. AB - BACKGROUND: As Intimate Partner Violence (IPV) affects the workplace, a supportive workplace climate is important. The study evaluated the effectiveness of an "IPV and the Workplace" training on workplace climate towards IPV. METHODS: IPV training was provided to 14 intervention counties and 13 control counties (receiving training 6 months delayed). Measures included workplace climate surveys, IPV knowledge test, and workplace observations. RESULTS: (i) Training significantly improved supervisor knowledge on IPV and received positive evaluations, (ii) training improved workplace climate towards IPV significantly which was maintained over time, and (iii) after the training, supervisors provided more IPV information to employees and more IPV postings were available in the workplace. CONCLUSIONS: The study provides evidence to support on-site interactive, computer based training as a means for improved workplace safety. IPV and the Workplace training effectively increased knowledge and positively changed workplace climate. Am. J. Ind. Med. 59:538-548, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27195811 TI - Protein biomarker discovery and fast monitoring for the identification and detection of Anisakids by parallel reaction monitoring (PRM) mass spectrometry. AB - Anisakids are fish-borne parasites that are responsible for a large number of human infections and allergic reactions around the world. World health organizations and food safety authorities aim to control and prevent this emerging health problem. In the present work, a new method for the fast monitoring of these parasites is described. The strategy is divided in three steps: (i) purification of thermostable proteins from fish-borne parasites (Anisakids), (ii) in-solution HIFU trypsin digestion and (iii) monitoring of several peptide markers by parallel reaction monitoring (PRM) mass spectrometry. This methodology allows the fast detection of Anisakids in <2h. An affordable assay utilizing this methodology will facilitate testing for regulatory and safety applications. SIGNIFICANCE: The work describes for the first time, the Protein Biomarker Discovery and the Fast Monitoring for the identification and detection of Anisakids in fishery products. The strategy is based on the purification of thermostable proteins, the use of accelerated in-solution trypsin digestions under an ultrasonic field provided by High-Intensity Focused Ultrasound (HIFU) and the monitoring of several peptide biomarkers by Parallel Reaction Monitoring (PRM) Mass Spectrometry in a linear ion trap mass spectrometer. The workflow allows the unequivocal detection of Anisakids, in <2h. The present strategy constitutes the fastest method for Anisakids detection, whose application in the food quality control area, could provide to the authorities an effective and rapid method to guarantee the safety to the consumers. PMID- 27195810 TI - Manipulation of Cell Cycle and Chromatin Configuration by Means of Cell Penetrating Geminin. AB - Geminin regulates chromatin remodeling and DNA replication licensing which play an important role in regulating cellular proliferation and differentiation. Transcription of the Geminin gene is regulated via an E2F-responsive region, while the protein is being closely regulated by the ubiquitin-proteasome system. Our objective was to directly transduce Geminin protein into cells. Recombinant cell-penetrating Geminin (CP-Geminin) was generated by fusing Geminin with a membrane translocating motif from FGF4 and was efficiently incorporated into NIH 3T3 cells and mouse embryonic fibroblasts. The withdrawal study indicated that incorporated CP-Geminin was quickly reduced after removal from medium. We confirmed CP-Geminin was imported into the nucleus after incorporation and also that the incorporated CP-Geminin directly interacted with Cdt1 or Brahma/Brg1 as the same manner as Geminin. We further demonstrated that incorporated CP-Geminin suppressed S-phase progression of the cell cycle and reduced nuclease accessibility in the chromatin, probably through suppression of chromatin remodeling, indicating that CP-Geminin constitutes a novel tool for controlling chromatin configuration and the cell cycle. Since Geminin has been shown to be involved in regulation of stem cells and cancer cells, CP-Geminin is expected to be useful for elucidating the role of Geminin in stem cells and cancer cells, and for manipulating their activity. PMID- 27195812 TI - Mapping the Ca(2+) induced structural change in calreticulin. AB - Calreticulin is a highly conserved multifunctional protein implicated in many different biological systems and has therefore been the subject of intensive research. It is primarily present in the endoplasmatic reticulum where its main functions are to regulate Ca(2+) homeostasis, act as a chaperone and stabilize the MHC class I peptide-loading complex. Although several high-resolution structures of calreticulin exist, these only cover three-quarters of the entire protein leaving the extended structures unsolved. Additionally, the structure of calreticulin is influenced by the presence of Ca(2+). The conformational changes induced by Ca(2+) have not been determined yet as they are hard to study with traditional approaches. Here, we investigated the Ca(2+)-induced conformational changes with a combination of chemical cross-linking, mass spectrometry, bioinformatics analysis and modelling in Rosetta. Using a bifunctional linker, we found a large Ca(2+)-induced change to the cross-linking pattern in calreticulin. Our results are consistent with a high flexibility in the P-loop, a stabilization of the acidic C-terminal and a relatively close interaction of the P-loop and the acidic C-terminal. BIOLOGICAL SIGNIFICANCE: The function of calreticulin, an endoplasmatic reticulin chaperone, is affected by fluctuations in Ca(2+)concentration, but the structural mechanism is unknown. The present work suggests that Ca(2+)-dependent regulation is caused by different conformations of a long proline-rich loop that changes the accessibility to the peptide/lectin binding site. Our results indicate that the binding of Ca(2+) to calreticulin may thus not only just be a question of Ca(2+) storage but is likely to have an impact on the chaperone activity. PMID- 27195813 TI - Quantitative proteomic analysis of two different rice varieties reveals that drought tolerance is correlated with reduced abundance of photosynthetic machinery and increased abundance of ClpD1 protease. AB - Rice is the major staple food for more than half of world's population. As global climate changes, we are observing more floods, droughts and severe heat waves. Two rice cultivars with contrasting genetic backgrounds and levels of tolerance to drought, Nipponbare and IAC1131, were used in this study. Four-week-old seedlings of both cultivars were grown in large soil volumes and then exposed to moderate and extreme drought for 7days, followed by 3days of re-watering. Mature leaves were harvested from plants from each treatment for protein extraction and subsequent shotgun proteomic analysis, with validation of selected proteins by western blotting. Gene Ontology (GO) annotations of differentially expressed proteins provide insights into the metabolic pathways that are involved in drought stress resistance. Our data indicate that IAC1131 appears to be better able to cope with stressful conditions by upregulating a suite of stress and defence response related proteins. Nipponbare, in contrast, lacks the range of stress responses shown by the more stress tolerant variety, and responds to drought stress by initiating a partial shutdown of chlorophyll biosynthesis in an apparent attempt to preserve resources. SIGNIFICANCE: In this study, two rice genotypes with contrasting drought tolerance were exposed to soil water deficits, and proteomic changes were observed in mature leaf laminae. Plants were well watered and then switched to conditions of either moderate drought or extreme drought followed by three days of recovery. Proteins were identified and quantified using both label-free and Tandem Mass Tag multiplexing approaches. Several biochemical pathways were significantly altered in response to water deficit. Most notably, the up-regulation of ClpD1 protease responded strongly in the drought-tolerant landrace; this protein is typically involved in heat and osmotic stress response. In contrast, porphyrin and chlorophyll biosynthesis pathways were down-regulated, indicating suppression of the photosynthetic machinery. PMID- 27195817 TI - ERRATUM: Section E6.1-6.4 of the ACMG technical standards and guidelines: chromosome studies of neoplastic blood and bone marrow-acquired chromosomal abnormalities. PMID- 27195814 TI - Intensive vs Standard Blood Pressure Control and Cardiovascular Disease Outcomes in Adults Aged >=75 Years: A Randomized Clinical Trial. AB - IMPORTANCE: The appropriate treatment target for systolic blood pressure (SBP) in older patients with hypertension remains uncertain. OBJECTIVE: To evaluate the effects of intensive (<120 mm Hg) compared with standard (<140 mm Hg) SBP targets in persons aged 75 years or older with hypertension but without diabetes. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, randomized clinical trial of patients aged 75 years or older who participated in the Systolic Blood Pressure Intervention Trial (SPRINT). Recruitment began on October 20, 2010, and follow-up ended on August 20, 2015. INTERVENTIONS: Participants were randomized to an SBP target of less than 120 mm Hg (intensive treatment group, n = 1317) or an SBP target of less than 140 mm Hg (standard treatment group, n = 1319). MAIN OUTCOMES AND MEASURES: The primary cardiovascular disease outcome was a composite of nonfatal myocardial infarction, acute coronary syndrome not resulting in a myocardial infarction, nonfatal stroke, nonfatal acute decompensated heart failure, and death from cardiovascular causes. All-cause mortality was a secondary outcome. RESULTS: Among 2636 participants (mean age, 79.9 years; 37.9% women), 2510 (95.2%) provided complete follow-up data. At a median follow-up of 3.14 years, there was a significantly lower rate of the primary composite outcome (102 events in the intensive treatment group vs 148 events in the standard treatment group; hazard ratio [HR], 0.66 [95% CI, 0.51-0.85]) and all-cause mortality (73 deaths vs 107 deaths, respectively; HR, 0.67 [95% CI, 0.49-0.91]). The overall rate of serious adverse events was not different between treatment groups (48.4% in the intensive treatment group vs 48.3% in the standard treatment group; HR, 0.99 [95% CI, 0.89-1.11]). Absolute rates of hypotension were 2.4% in the intensive treatment group vs 1.4% in the standard treatment group (HR, 1.71 [95% CI, 0.97-3.09]), 3.0% vs 2.4%, respectively, for syncope (HR, 1.23 [95% CI, 0.76-2.00]), 4.0% vs 2.7% for electrolyte abnormalities (HR, 1.51 [95% CI, 0.99 2.33]), 5.5% vs 4.0% for acute kidney injury (HR, 1.41 [95% CI, 0.98-2.04]), and 4.9% vs 5.5% for injurious falls (HR, 0.91 [95% CI, 0.65-1.29]). CONCLUSIONS AND RELEVANCE: Among ambulatory adults aged 75 years or older, treating to an SBP target of less than 120 mm Hg compared with an SBP target of less than 140 mm Hg resulted in significantly lower rates of fatal and nonfatal major cardiovascular events and death from any cause. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01206062. PMID- 27195815 TI - Molecular characterization of NRXN1 deletions from 19,263 clinical microarray cases identifies exons important for neurodevelopmental disease expression. AB - PURPOSE: The purpose of the current study was to assess the penetrance of NRXN1 deletions. METHODS: We compared the prevalence and genomic extent of NRXN1 deletions identified among 19,263 clinically referred cases to that of 15,264 controls. The burden of additional clinically relevant copy-number variations (CNVs) was used as a proxy to estimate the relative penetrance of NRXN1 deletions. RESULTS: We identified 41 (0.21%) previously unreported exonic NRXN1 deletions ascertained for developmental delay/intellectual disability that were significantly greater than in controls (odds ratio (OR) = 8.14; 95% confidence interval (CI): 2.91-22.72; P < 0.0001). Ten (22.7%) of these had a second clinically relevant CNV. Subjects with a deletion near the 3' end of NRXN1 were significantly more likely to have a second rare CNV than subjects with a 5' NRXN1 deletion (OR = 7.47; 95% CI: 2.36-23.61; P = 0.0006). The prevalence of intronic NRXN1 deletions was not statistically different between cases and controls (P = 0.618). The majority (63.2%) of intronic NRXN1 deletion cases had a second rare CNV at a prevalence twice as high as that for exonic NRXN1 deletion cases (P = 0.0035). CONCLUSIONS: The results support the importance of exons near the 5' end of NRXN1 in the expression of neurodevelopmental disorders. Intronic NRXN1 deletions do not appear to substantially increase the risk for clinical phenotypes.Genet Med 19 1, 53-61. PMID- 27195818 TI - Is it Fabry disease? AB - Fabry disease is caused by mutations in the GLA gene that lower alpha galactosidase A activity to less than 25-30% of the mean normal level. Several GLA variants have been identified that are associated with relatively elevated residual alpha-galactosidase A. The challenge is to determine which GLA variants can cause clinical manifestations related to Fabry disease. Here, we review the various types of GLA variants and recommend that pathogenicity be considered only when associated with elevated globotriaosylceramide in disease-relevant organs and tissues as analyzed by mass spectrometry. This criterion is necessary to ensure that very costly and specific therapy is provided only when appropriate.Genet Med 18 12, 1181-1185. PMID- 27195816 TI - The phenotypic spectrum of Schaaf-Yang syndrome: 18 new affected individuals from 14 families. AB - PURPOSE: Truncating mutations in the maternally imprinted, paternally expressed gene MAGEL2, which is located in the Prader-Willi critical region 15q11-13, have recently been reported to cause Schaaf-Yang syndrome, a Prader-Willi-like disease that manifests as developmental delay/intellectual disability, hypotonia, feeding difficulties, and autism spectrum disorder. The causality of the reported variants in the context of the patients' phenotypes was questioned, as MAGEL2 whole-gene deletions seem to cause little or no clinical phenotype. METHODS: Here we report a total of 18 newly identified individuals with Schaaf-Yang syndrome from 14 families, including 1 family with 3 individuals found to be affected with a truncating variant of MAGEL2, 11 individuals who are clinically affected but were not tested molecularly, and a presymptomatic fetal sibling carrying the pathogenic MAGEL2 variant. RESULTS: All cases harbor truncating mutations of MAGEL2, and nucleotides c.1990-1996 arise as a mutational hotspot, with 10 individuals and 1 fetus harboring a c.1996dupC (p.Q666fs) mutation and 2 fetuses harboring a c.1996delC (p.Q666fs) mutation. The phenotypic spectrum of Schaaf Yang syndrome ranges from fetal akinesia to neurobehavioral disease and contractures of the small finger joints. CONCLUSION: This study provides strong evidence for the pathogenicity of truncating mutations of the paternal allele of MAGEL2, refines the associated clinical phenotypes, and highlights implications for genetic counseling for affected families.Genet Med 19 1, 45-52. PMID- 27195819 TI - Inborn Errors of Metabolism Collaborative: large-scale collection of data on long term follow-up for newborn-screened conditions. AB - PURPOSE: The Inborn Errors of Metabolism Information System (IBEM-IS) collects data on the clinical history of inborn errors of metabolism (IBEMs). The IBEM-IS is accessible to metabolic clinics nationwide and seeks to (i) influence clinical management of affected individuals and (ii) provide information to support public health decision making. METHODS: Thirty centers in 21 states are enrolling persons with newborn-screened conditions, collecting information on diagnosis and treatment at the time of enrollment and all subsequent visits. Prospective data are collected using electronic capture forms allowing aggregation of information regarding outcomes for individuals affected with IBEMs. RESULTS: A total of 1,893 subjects have been enrolled in the IBEM-IS, and more than 540,000 individual data points have been collected. Data collection has been initiated for subjects with 41 of 46 conditions on the recommended uniform screening panel; 4 conditions have more than 100 subjects enrolled. Median follow-up time for subjects with more than one visit (n = 898) is 1.5 years (interquartile range = 2.2 years). Subjects with critical conditions are more likely to have emergency letters and sick-day plans. Mortality was exclusive to children with critical conditions. CONCLUSION: Large-scale prospective data can be collected for individuals with rare conditions, permitting enhanced decision making for clinical management and supporting decision making in public health newborn screening programs.Genet Med 18 12, 1276-1281. PMID- 27195820 TI - Short- and long-term effects of the use of RAAS blockers immediately after renal transplantation. AB - BACKGROUND: The efficacy and safety of renin angiotensin aldosterone system blockers (RAASB's) if introduced immediately after renal transplantation have not been extensively investigated. METHODS: The medical charts of 142 kidney transplant recipients who received a RAASB in the early postoperative period and of 114 matched controls were analyzed. The RAASB was given primarily for blood pressure control. RESULTS: 117 patients continued to receive and 50 controls remained continuously free of the RAASB in the first year. The RAASB was added on average at postoperative day 8 and the mean duration of follow-up was 5.4 years. Systolic, blood pressure at treatment initiation was increased in the RAASB group (150 +/- 17 vs. 141 +/- 16, p < 0.001). At discharge from hospital and during follow-up blood pressure was similar in both groups, without differences in GFR, potassium and proteinuria. The endpoints "graft failure" and "graft failure or death from any cause" were significantly better in patients treated with RAASB's (p = 0.03 and p = 0.04, respectively). The treatment effects in the RAASB group persisted even after adjustment for demographic parameters, immunological risk factors, peritransplant risk factors, duration of dialysis prior to transplantation and medical comorbidities. CONCLUSIONS: Thus, RAASB's can be used effectively and safely to treat hypertension in the early postoperative period after kidney transplantation and are renoprotective in the long term. PMID- 27195821 TI - Genetic Diversity, Natural Selection and Haplotype Grouping of Plasmodium knowlesi Gamma Protein Region II (PkgammaRII): Comparison with the Duffy Binding Protein (PkDBPalphaRII). AB - BACKGROUND: Plasmodium knowlesi is a simian malaria parasite that has been reported to cause malaria in humans in Southeast Asia. This parasite invades the erythrocytes of humans and of its natural host, the macaque Macaca fascicularis, via interaction between the Duffy binding protein region II (PkDBPalphaRII) and the Duffy antigen receptor on the host erythrocytes. In contrast, the P. knowlesi gamma protein region II (PkgammaRII) is not involved in the invasion of P. knowlesi into humans. PkgammaRII, however, mediates the invasion of P. knowlesi into the erythrocytes of M. mulata, a non-natural host of P. knowlesi via a hitherto unknown receptor. The haplotypes of PkDBPalphaRII in P. knowlesi isolates from Peninsular Malaysia and North Borneo have been shown to be genetically distinct and geographically clustered. Also, the PkDBPalphaRII was observed to be undergoing purifying (negative) selection. The present study aimed to determine whether similar phenomena occur in PkgammaRII. METHODS: Blood samples from 78 knowlesi malaria patients were used. Forty-eight of the samples were from Peninsular Malaysia, and 30 were from Malaysia Borneo. The genomic DNA of the samples was extracted and used as template for the PCR amplification of the PkgammaRII. The PCR product was cloned and sequenced. The sequences obtained were analysed for genetic diversity and natural selection using MEGA6 and DnaSP (version 5.10.00) programmes. Genetic differentiation between the PkgammaRII of Peninsular Malaysia and North Borneo isolates was estimated using the Wright's FST fixation index in DnaSP (version 5.10.00). Haplotype analysis was carried out using the Median-Joining approach in NETWORK (version 4.6.1.3). RESULTS: A total of 78 PkgammaRII sequences was obtained. Comparative analysis showed that the PkgammaRII have similar range of haplotype (Hd) and nucleotide diversity (pi) with that of PkDBPalphaRII. Other similarities between PkgammaRII and PkDBPalphaRII include undergoing purifying (negative) selection, geographical clustering of haplotypes, and high inter-population genetic differentiation (FST index). The main differences between PkgammaRII and PkDBPalphaRII include length polymorphism and no departure from neutrality (as measured by Tajima's D statistics) in the PkgammaRII. CONCLUSION: Despite the biological difference between PkgammaRII and PkDBPalphaRII, both generally have similar genetic diversity level, natural selection, geographical haplotype clustering and inter population genetic differentiation index. PMID- 27195822 TI - Topical application of spent coffee ground extracts protects skin from ultraviolet B-induced photoaging in hairless mice. AB - The aim of this study was to evaluate the protective effect of spent coffee ground (SCG) on ultraviolet (UV) B-induced photoaging in hairless mice. The oil fraction (OSCG) and ethanol extract (ESCG) of SCG were prepared from SCG. OSCG contained a much higher level of caffeine (547.32 +/- 1.68 MUg mg(-1)) when compared to the sum of its chlorogenic acid derivatives (~119 MUg mg(-1)), and pyrazines were the major aromatic compounds in OSCG. OSCG effectively inhibited the UVB-induced increase in intracellular reactive oxygen species in HaCaT cells. Topical application of OSCG or ESCG significantly reduced the UVB-induced wrinkle formation in mice dorsal skin. The combined application of OSCG and ESCG (OEH) led to a decrease in the wrinkle area by over 35% when compared with the UVB treated control (UVBC). Epidermal thickness was also reduced by 40%. This result was connected to the significant reduction in transdermal water loss (27%) and erythema formation (48%) that result from UVB irradiation. Polarization-sensitive optical coherence tomography (PS-OCT) and antibody-based histological analyses showed that OSCG and ESCG effectively suppressed the UVB-induced decrease in collagen content. The level of type 1 collagen (COL1) in the OEH group was enhanced by around 40% compared with the UVB control group (UVBC). This was attributed to the down-regulation of matrix metalloproteinases (MMP2, 9, and 13), which are known to be responsible for collagen destruction. Our results indicate that topical treatment with OSCG/ESCG protects mouse skin from UVB-induced photoaging by down-regulating MMPs; therefore, suggesting the potential of SCG extracts as a topical anti-photoaging agent. PMID- 27195824 TI - Contrasting Photophysiological Characteristics of Phytoplankton Assemblages in the Northern South China Sea. AB - The growth of phytoplankton and thus marine primary productivity depend on photophysiological performance of phytoplankton cells that respond to changing environmental conditions. The South China Sea (SCS) is the largest marginal sea of the western Pacific and plays important roles in modulating regional climate and carbon budget. However, little has been documented on photophysiological characteristics of phytoplankton in the SCS. For the first time, we investigated photophysiological characteristics of phytoplankton assemblages in the northern South China Sea (NSCS) using a real-time in-situ active chlorophyll a fluorometry, covering 4.0 * 105 km2. The functional absorption cross section of photosystem II (PSII) in darkness (sigmaPSII) or under ambient light (sigmaPSII') (A2 quanta-1) increased from the surface to deeper waters at all the stations during the survey period (29 July to 23 August 2012). While the maximum (Fv/Fm, measured in darkness) or effective (Fq'/Fm', measured under ambient light) photochemical efficiency of PSII appeared to increase with increasing depth at most stations, it showed inverse relationship with depth in river plume areas. The functional absorption cross section of PSII changes could be attributed to light-adapted genotypic feature due to niche-partition and the alteration of photochemical efficiency of PSII could be attributed to photo-acclimation. The chlorophyll a fluorometry can be taken as an analog to estimate primary productivity, since areas of higher photochemical efficiency of PSII coincided with those of higher primary productivity reported previously in the NSCS. PMID- 27195823 TI - Traditional Chinese medicines in the management of cardiovascular diseases: a comprehensive systematic review. AB - AIMS: The aim was to perform a systematic review of the efficacy of traditional Chinese medicines (TCM) in cardiovascular disease. METHODS: Electronic databases were searched up to 11 November 2015 for all randomized-controlled trials evaluating the effect of TCM in hypertension, ischaemic stroke, heart failure, coronary heart disease and type 2 diabetes mellitus. Pooled odds ratios (ORs) were calculated using a fixed-effects model. RESULTS: Four hypertension studies were eligible for statistical analysis and included 133 patients receiving TCM and 130 control patients. There were significant reductions in systolic blood pressure in patients receiving TCM, comparable to results achieved with pharmaceutical medicines. An OR of 3.781 (95% confidence interval 2.392, 5.977; P = 0.000) was observed for the anti-hypertensive effect of TCM. Significant heterogeneity was present (P = 0.011), with a tendency towards publication bias that did not reach significance (P = 0.05275). Outcome measures for other cardiovascular diseases were inconsistent. CONCLUSIONS: Certain TCM compounds appear to have significant anti-hypertensive effects, and although some are associated in some studies with improved outcomes in coronary heart disease, heart failure and type 2 diabetes mellitus, the data are inconsistent and will require large-scale randomized-controlled trials to allow full evaluation of any potential therapeutic benefit in these areas. PMID- 27195825 TI - Attention selectively modulates cortical entrainment in different regions of the speech spectrum. AB - Recent studies have uncovered a neural response that appears to track the envelope of speech, and have shown that this tracking process is mediated by attention. It has been argued that this tracking reflects a process of phase locking to the fluctuations of stimulus energy, ensuring that this energy arrives during periods of high neuronal excitability. Because all acoustic stimuli are decomposed into spectral channels at the cochlea, and this spectral decomposition is maintained along the ascending auditory pathway and into auditory cortex, we hypothesized that the overall stimulus envelope is not as relevant to cortical processing as the individual frequency channels; attention may be mediating envelope tracking differentially across these spectral channels. To test this we reanalyzed data reported by Horton et al. (2013), where high-density EEG was recorded while adults attended to one of two competing naturalistic speech streams. In order to simulate cochlear filtering, the stimuli were passed through a gammatone filterbank, and temporal envelopes were extracted at each filter output. Following Horton et al. (2013), the attended and unattended envelopes were cross-correlated with the EEG, and local maxima were extracted at three different latency ranges corresponding to distinct peaks in the cross-correlation function (N1, P2, and N2). We found that the ratio between the attended and unattended cross-correlation functions varied across frequency channels in the N1 latency range, consistent with the hypothesis that attention differentially modulates envelope-tracking activity across spectral channels. PMID- 27195826 TI - Development of antithrombotic nanoconjugate blocking integrin alpha2beta1 collagen interactions. AB - An antithrombotic nanoconjugate was designed in which a designed biomimetic peptide LWWNSYY was immobilized to the surface of poly(glycidyl methacrylate) nanoparticles (PGMA NPs). Our previous work has demonstrated LWWNSYY to be an effective inhibitor of integrin alpha2beta1-collagen interaction and subsequent thrombus formation, however its practical application suffered from the formation of clusters in physiological environment caused by its high hydrophobicity. In our present study, the obtained LWWNSYY-PGMA nanoparticles (L-PGMA NPs) conjugate, with an improved dispersibility of LWWNSYY by PGMA NPs, have shown binding to collagen receptors with a Kd of 3.45 +/- 1.06 MUM. L-PGMA NPs have also proven capable of inhibiting platelet adhesion in vitro with a reduced IC50 of 1.83 +/- 0.29 MUg/mL. High inhibition efficiency of L-PGMA NPs in thrombus formation was further confirmed in vivo with a 50% reduction of thrombus weight. Therefore, L-PGMA NPs were developed as a high-efficiency antithrombotic nanomedicine targeted for collagen exposed on diseased blood vessel wall. PMID- 27195892 TI - Molecular Characterization of Shigella sonnei: An Increasingly Prevalent Etiologic Agent of Shigellosis in Guizhou Province, Southwest of China. AB - BACKGROUND: Shigellosis is a serious problem in Guizhou and Shigella sonnei is an increasingly prevalent etiologic agent of local shigellosis cases. No data, however, are available about the molecular characterization of the local isolates of S. sonnei. We have conducted this study to molecularly characterize the clinical isolates of S. sonnei in Guizhou Province. RESULTS: 76 S. sonnei isolates, including four isolates from 1974-1982 and 72 isolates from 2008-2010, were used for analysis in this study. Pulsed-field gel electrophoresis (PFGE) based on XbaI digestion divided the 76 isolates into 38 PFGE patterns (PT) and 15 PTs were represented by more than one isolates with PT31 (N = 8) containing the most number of isolates, followed with PT2 (N = 6). Multiple-Locus Variable number tandem repeat (VNTR) Analysis (MLVA) based on seven VNTR loci discriminated them into 19 different MLVA types (MTs), and four MTs were represented by more than one isolate with MT4 (N = 39) containing the most number of isolates, followed with MT12 (N = 18). 15 Multilocus sequence typing (MLST) base on 15 loci differentiated the isolates into six sequence types (STs), among which four STs were novel. The most common STs are ST76 (N = 43) and ST116 (N = 25), accounting for 92.1%. Correlation between genetic relationships and geographical origins or isolation years was observed among the isolates studied. Majority of isolates were clustered in accordance with the origin of isolation years based on the genetic data, which were also from similar geographical origins. CONCLUSIONS: Our results revealed the molecular characteristics including the specific genotypes such as four novel STs, clonal relationship, and genetic changes of local isolates from different years, which enhances our understanding of molecular characteristics of S. sonnei and contributes to the prevention and control of shigellosis in Guizhou Province. PMID- 27195893 TI - Risk factors for death in children with severe hand, foot, and mouth disease in Hunan, China. AB - BACKGROUND: In recent years, outbreaks of hand, foot, and mouth disease (HFMD) have increased throughout East and Southeast Asia, especially in mainland China. The disease now presents as an increasingly serious public health threat in China. METHODS: A case-control study was designed to examine risk factors associated with death from severe HFMD. A total of 553 severe HFMD cases were collected from the National Surveillance System. RESULTS: Multifactorial logistic regression was used to analyse independent associations between potential influence factors and death from severe HFMD. We found that the migrants were more likely to die from severe HFMD than the resident population (OR = 3.07, 95%CI: 1.39-8.32). Additionally, the children whose first visit was to a village level clinic had a high risk of death from severe HFMD. Patients with EV71 infection or symptoms of convulsion, dyspnoea, cyanosis, coolness of extremities, and vomiting had an increased risk of death from severe HFMD. While breastfeeding children, having a confirmed diagnosis at the first visit to the hospital and with symptom of hyperarousal were identified as protective factors for death from severe HFMD. CONCLUSIONS: To reduce the mortality from severe HFMD, doctors and health care providers need to pay attention to the patients with EV71 infection or with symptoms of convulsion, dyspnoea, cyanosis, coolness of extremities, and vomiting. Health administration departments should pay more attention to the rational allocation of health resources. Furthermore, they should increase financial support and manpower in village-level health institutions. PMID- 27195895 TI - The Academy of Breastfeeding Medicine's Signature Product: Our Clinical Protocols. PMID- 27195891 TI - Conserved Units of Co-Expression in Bacterial Genomes: An Evolutionary Insight into Transcriptional Regulation. AB - Genome-wide measurements of transcriptional activity in bacteria indicate that the transcription of successive genes is strongly correlated beyond the scale of operons. Here, we analyze hundreds of bacterial genomes to identify supra operonic segments of genes that are proximal in a large number of genomes. We show that these synteny segments correspond to genomic units of strong transcriptional co-expression. Structurally, the segments contain operons with specific relative orientations (co-directional or divergent) and nucleoid associated proteins are found to bind at their boundaries. Functionally, operons inside a same segment are highly co-expressed even in the apparent absence of regulatory factors at their promoter regions. Remote operons along DNA can also be co-expressed if their corresponding segments share a transcriptional or sigma factor, without requiring these factors to bind directly to the promoters of the operons. As evidence that these results apply across the bacterial kingdom, we demonstrate them both in the Gram-negative bacterium Escherichia coli and in the Gram-positive bacterium Bacillus subtilis. The underlying process that we propose involves only RNA-polymerases and DNA: it implies that the transcription of an operon mechanically enhances the transcription of adjacent operons. In support of a primary role of this regulation by facilitated co-transcription, we show that the transcription en bloc of successive operons as a result of transcriptional read-through is strongly and specifically enhanced in synteny segments. Finally, our analysis indicates that facilitated co-transcription may be evolutionary primitive and may apply beyond bacteria. PMID- 27195894 TI - Noise Annoyance Is Associated with Depression and Anxiety in the General Population- The Contribution of Aircraft Noise. AB - BACKGROUND: While noise annoyance has become recognized as an important environmental stressor, its association to mental health has hardly been studied. We therefore determined the association of noise annoyance to anxiety and depression and explored the contribution of diverse environmental sources to overall noise annoyance. PATIENTS AND METHODS: We investigated cross-sectional data of n = 15.010 participants of the Gutenberg Health Study (GHS), a population based, prospective, single-center cohort study in Mid-Germany (age 35 to 74 years). Noise annoyance was assessed separately for road traffic, aircraft, railways, industrial, neighborhood indoor and outdoor noise ("during the day"; "in your sleep") on 5-point scales ("not at all" to "extremely"); depression and anxiety were assessed by the PHQ-9, resp. GAD-2. RESULTS: Depression and anxiety increased with the degree of overall noise annoyance. Compared to no annoyance, prevalence ratios for depression, respectively anxiety increased from moderate (PR depression 1.20; 95%CI 1.00 to 1.45; PR anxiety 1.42; 95% CI 1.15 to 1.74) to extreme annoyance (PR depression 1.97; 95%CI 1.62 to 2.39; PR anxiety 2.14; 95% CI 1.71 to 2.67). Compared to other sources, aircraft noise annoyance was prominent affecting almost 60% of the population. INTERPRETATION: Strong noise annoyance was associated with a two-fold higher prevalence of depression and anxiety in the general population. While we could not relate annoyance due to aircraft noise directly to depression and anxiety, we established that it was the major source of annoyance in the sample, exceeding the other sources in those strongly annoyed. Prospective follow-up data will address the issue of causal relationships between annoyance and mental health. PMID- 27195896 TI - Dopamine receptor polymorphism modulates the relation between antenatal maternal anxiety and fetal movement. AB - We determined whether the combination of fetal genotype (dopamine D4 receptor; DRD4) and mothers' anxiety during pregnancy is associated with fetal behavior. Two hundred and six pregnant women underwent an ultrasound exam. Fetal movement measures (Movement Frequency, Total Activity, Movement Duration, and Longest Quiet Time) were derived from off-line coding. A moderating role of the DRD4-III polymorphism was found: Results indicate that higher levels of antenatal maternal anxiety symptoms were associated with more frequent fetal movements among fetuses carrying a 7R allele, but not among fetuses carrying shorter alleles. Total Activity did not show full moderation by DRD4, though the measure was correlated with maternal anxiety among fetuses in the Anxious Group with a 7R allele; not among fetuses without both factors. The findings provide the first evidence of a GXE interaction in association with fetal behavior. Results also demonstrate that some individuals are inherently more susceptible to uterine environmental influences than are others. PMID- 27195898 TI - Violence against women and cervical cancer screening: a systematic review. AB - AIMS AND OBJECTIVES: To present a systematic review of papers published on the relationship between violence against women and cervical cancer screening. BACKGROUND: Violence against women is a serious public health problem. This phenomenon can have negative effects on victims' health and affect the frequency at which they receive cervical cancer screening. DESIGN: A systematic literature review. METHODS: This study was carried out in October 2015 with searches of the Lilacs, PubMed and Web of Science databases using the following keywords: violence, domestic violence, battered women, spouse abuse, Papanicolaou test, vaginal smears, early detection of cancer and cervix uteri. RESULTS: Eight papers published between 2002-2013 were included in this review, most of which were cross-sectional studies. Three studies found no association between victimisation and receiving Pap testing, and five studies reported an association. These contradictory results were due to higher or lower examination frequencies among the women who had experienced violence. CONCLUSION: The results of this study indicate that the association between violence against women and cervical cancer screening remains inconclusive, and they demonstrate the need for more detailed studies to help clarify this relationship. RELEVANCE TO CLINICAL PRACTICE: Professionals who aid women should be knowledgeable regarding the perception and detection of violence so that they can interrupt the cycle of aggression, which has harmful impacts on victims' health. PMID- 27195899 TI - Diffusiophoretic mobility of charge-regulating porous particles. AB - The diffusiophoresis of a charge-regulating porous sphere, such as polyelectrolyte coil, with an arbitrary thickness of the electric double layer in an electrolyte solution prescribed with a concentration gradient is analytically studied for the first time. The ionogenic functional groups and hydrodynamic frictional segments distribute uniformly within the permeable particle, and a charge regulation model for the association and dissociation reactions of the functional groups relates the fixed charge density to the local electric potential. The electrokinetic equations governing the electric potential, ionic electrochemical potential, and fluid velocity distributions are solved as power series expansions in the basic fixed charge density. An explicit formula for the diffusiophoretic mobility of the particle, which vanishes at the isoelectric point, is derived from a force balance. The effects of charge regulation on the diffusiophoretic mobility, which depend on various particle and electrolyte characteristics such as the reaction equilibrium constants of the ionogenic functional groups, are significant and interesting. The variation in the bulk concentration of the charge-determining ions can produce more than one reversal in the direction of the diffusiophoretic velocity. The obtained results differ conspicuously from those of impermeable particles and provide valuable information for the interpretation of experimental data. PMID- 27195901 TI - Self-Efficacy, Planning, and Drink Driving: Applying the Health Action Process Approach. AB - OBJECTIVE: This study examines the constructs from the health action process approach (HAPA) theoretical model (Schwarzer, 1992) on future drink driving avoidance by first time drink driving offenders. This research presents an advance in health related theory by the novel application of the health model to predict risk avoidance. METHOD: Baseline interviews were conducted with 198 first time drink driving offenders at the time of court appearance, and offenders were followed up 6-8 months following the offense date. The key outcome variables used in 3 stages were behavioral expectation, planning, and self-reported avoidance of drink driving at follow-up. RESULTS: Bivariate and multivariate analyses were conducted for each stage. High task self-efficacy and female gender were significantly related to having no behavioral expectation of future drink driving. High maintenance self-efficacy was significantly related to high levels of planning to avoid future drink driving. Those with higher planning scores at baseline had significantly higher odds of reporting that they had avoided drink driving at follow up. CONCLUSION: Planning plays an important role in drink driving rehabilitation and should be a focus of early intervention programs aimed at reducing drink driving recidivism following a first offense. Self-efficacy is an important construct to consider for the behavior and could strengthen a planning focused intervention. (PsycINFO Database Record PMID- 27195900 TI - Change in health-related quality of life in the context of pediatric obesity interventions: A meta-analytic review. AB - OBJECTIVE: To quantitatively characterize change in health-related quality of life (HRQoL) in the context of behavioral (n = 16), surgical (n = 5), and pharmacological (n = 1) interventions for pediatric overweight and obesity. A secondary goal was to examine the relationship between change in HRQoL and change in body mass index (DeltaBMI) by treatment type. The amount of weight loss necessary to observe a minimally clinically important difference (MCID) in HRQoL was determined. METHOD: Data were gathered from studies reporting on weight change and DeltaHRQoL over the course of obesity interventions (N = 22) in youths (N = 1,332) with average ages between 7.4 and 16.5 years (M = 12.2). An overall effect size was calculated for DeltaHRQoL. Moderation analyses were conducted using analysis of variance and weighted regression. MCID analyses were conducted by converting HRQoL data to standard error of measurement units. RESULTS: The overall effect size for DeltaHRQoL in the context of pediatric obesity interventions was medium (g = 0.51). A significant linear relationship was detected between DeltaBMI and DeltaHRQoL (R2 = 0.87). This relationship was moderated by treatment type, with medical (i.e., surgical) interventions demonstrating a stronger relationship. Results indicated that it takes a change of 0.998 BMI units to detect true change in HRQoL. CONCLUSION: This study provides the first known quantitative examination of changes in HRQoL associated with weight loss in pediatric interventions. Medical interventions appear to offer a more substantial increase in HRQoL per unit of BMI change. These results offer a concrete weight loss goal for noticing positive effects in daily life activities. (PsycINFO Database Record PMID- 27195897 TI - Polymyxin Resistance in Acinetobacter baumannii: Genetic Mutations and Transcriptomic Changes in Response to Clinically Relevant Dosage Regimens. AB - Polymyxins are often last-line therapeutic agents used to treat infections caused by multidrug-resistant A. baumannii. Recent reports of polymyxin-resistant A. baumannii highlight the urgent need for research into mechanisms of polymyxin resistance. This study employed genomic and transcriptomic analyses to investigate the mechanisms of polymyxin resistance in A. baumannii AB307-0294 using an in vitro dynamic model to mimic four different clinically relevant dosage regimens of polymyxin B and colistin over 96 h. Polymyxin B dosage regimens that achieved peak concentrations above 1 mg/L within 1 h caused significant bacterial killing (~5 log10CFU/mL), while the gradual accumulation of colistin resulted in no bacterial killing. Polymyxin resistance was observed across all dosage regimens; partial reversion to susceptibility was observed in 6 of 8 bacterial samples during drug-free passaging. Stable polymyxin-resistant samples contained a mutation in pmrB. The transcriptomes of stable and non-stable polymyxin-resistant samples were not substantially different and featured altered expression of genes associated with outer membrane structure and biogenesis. These findings were further supported via integrated analysis of previously published transcriptomics data from strain ATCC19606. Our results provide a foundation for understanding the mechanisms of polymyxin resistance following exposure to polymyxins and the need to explore effective combination therapies. PMID- 27195903 TI - Laboratory diagnosis of anemia: are the old and new red cell parameters useful in classification and treatment, how? AB - INTRODUCTION: Anemia is a global problem affecting the population in both developing and developed countries, and there is a debate on which hemoglobin level limit should be used to define anemia in general population and particularly in the elderly. We present herein a laboratory approach to diagnosing the possible causes of anemia based on traditional and new erythroid parameters. In this article, we provide practical diagnostic algorithms that address to differential diagnosis of anemia. Based on both morphological and kinetic classifications, three patterns were considered: microcytic, normocytic, and macrocytic. METHODS: Main interest is on the clinical usefulness of old and new parameters such as mean cell volume (MCV), red blood cell distribution width (RDW), hypochromic and microcytic erythrocytes, immature reticulocyte fraction (IRF), and some reticulocyte indices such as reticulocyte hemoglobin content and mean reticulocyte volume. The pathophysiologic basis is reviewed in terms of bone marrow erythropoiesis, evaluated by reticulocyte count (increased or normal/decreased) and IRF. The utility of reticulocyte indices in the diagnosis of iron-deficient erythropoiesis (absolute or functional) and in monitoring of response to treatment in nutritional anemia (iron and cobalamin) was also investigated. RESULTS: For each parameter, the availability, the possible clinical applications, and the limitations were evaluated. A discussion on intraindividual biological variation and its implication on the usefulness of conventional reference intervals and in longitudinal monitoring of the patients was also reported. CONCLUSION: Red cell parameters and reticulocyte indices play an essential role in differential diagnosis of anemia and in its treatment. More efforts are needed in harmonizing parameters whose results are still too different when produced by different analyzers. PMID- 27195902 TI - An Altered Perception of Normal: Understanding Causes for Treatment Delay in Women with Symptomatic Uterine Fibroids. AB - BACKGROUND: Uterine fibroids are benign tumors that are the leading cause of hysterectomy in the United States. Despite their high prevalence and associated morbidity, there are little qualitative data characterizing what drives women's treatment-seeking behavior for their fibroids. METHODS: Women with symptomatic or recently treated uterine fibroids completed in-depth interviews and demographic surveys. Interviews were transcribed verbatim and uploaded to NVivo version 10 for data management and thematic coding. Coders identified major themes and subthemes that emerged from the interviews. RESULTS: Sixty women (n = 60) completed the interviews. The kappa among coders was 0.94. The mean age of participants was 43.0 +/- 6.8. 61.7% of participants self-identified as African American, 25.0% as Caucasian, 8.3% as Hispanic, and 5.0% as Asian. Many women reported obtaining a delayed diagnosis for their uterine fibroids despite experiencing severe symptoms. There were five subthemes that identified why women delayed seeking treatment, which included the perception that their symptoms were "normal," they had a low knowledge of fibroids, they did not perceive themselves to be at risk for fibroids, they engaged in avoidance-based coping strategies, and/or they dissociated themselves from their fibroids. CONCLUSIONS: Many women with symptomatic fibroids live with this condition chronically without seeking care. It appears that for some, limited knowledge regarding fibroids and normal menstruation may lead to a distorted view of what is normal with regard to uterine bleeding, resulting in limited treatment seeking behavior. Others know their symptoms are abnormal but simply avoid the problem. There is a need for patient-centered and community-based education to improve women's knowledge of fibroids and symptoms and to promote treatment options. PMID- 27195904 TI - Enhanced Microwave Hyperthermia of Cancer Cells with Fullerene. AB - Hyperthermia generated with various energy sources including microwave has been widely studied for cancer treatment. However, the potential damage due to nontargeted heating of normal tissue is a major hurdle to its widespread application. Fullerene is a potential agent for improving cancer therapy with microwave hyperthermia but is limited by its poor solubility in water for biomedical applications. Here we report a combination therapy for enhanced cancer cell destruction by combining microwave heating with C60-PCNPs consisting of fullerene (C60) encapsulated in Pluronic F127-chitosan nanoparticles (PCNPs) with high water solubility. A cell culture dish integrated with an antenna was fabricated to generate microwave (2.7 GHz) for heating PC-3 human prostate cancer cells either with or without the C60-PCNPs. The cell viability data show that the C60-PCNPs alone have minimal cytotoxicity. The combination of microwave heating and C60-PCNPs is significantly more effective than the microwave heating alone in killing the cancer cells (7.5 versus 42.2% cell survival). Moreover, the combination of microwave heating and C60-PCNPs is significantly more destructive to the cancer cells than the combination of simple water-bath heating (with a similar thermal history to microwave heating) and C60-PCNPs (7.5 versus 32.5% survival) because the C60 in the many nanoparticles taken up by the cells can absorb the microwave energy and convert it into heat to enhance heating inside the cells under microwave irradiation. These data suggest the great potential of targeted heating via fullerene for enhanced cancer treatment by microwave hyperthermia. PMID- 27195905 TI - Is Extended Sedation Necessary for Young Children Receiving High-Dose (131) I MIBG Therapy? PMID- 27195906 TI - Phosphatase PPM1A is a novel prognostic marker in pancreatic ductal adenocarcinoma. AB - Pancreatic ductal adenocarcinoma (PDAC) harbors complex molecular alterations and remains a lethal disease. Aberrant TGF-beta/Smads signaling is a well-known mechanism involved in the progression of PDACs. However, loss of Smad4 expression is reported in only ~50% of PDACs and is generally associated with worse prognosis. Investigating additional prognostic markers is warranted. PPM1A is a phosphatase that dephosphorylates TGF-beta-activated Smad2/3 and inactivates the TGF-beta signaling. Little is known about the clinical significance of PPM1A in PDACs and its functional relationship to Smad4. In this study, PPM1A and Smad4 immunohistochemistry was assessed in 180 R0 resected human PDACs. PPM1A was lost in 41.7% cases, whereas Smad4 was lost in 45.7% cases. The median survival rate with negative and positive PPM1A was 10.9 and 16.8 months, respectively. Loss of PPM1A was significantly associated with larger tumor size and higher stage and was an independent predictor of unfavorable outcomes. Intriguingly, the overall survival of this cohort was divided into 3 groups based on the expression pattern of PPM1A and Smad4, with the Smad4+/PPM1A+ pattern associated with favorable survival, the Smad4+/PPM1A- or Smad4-/PPM1A- pattern associated with unfavorable, and the PPM1A+/Smad4- pattern fell between these 2 groups. In 82 cases with negative Smad4, PPM1A or P-Smad2/3 expression was retained. Using a SMAD4 deficient human PDAC cell line, BxPC3, we further demonstrated that TGF-beta1 treatment induced PPM1A and P-Smad2/3 expression in this cell line. PPM1A and Smad4 immunohistochemistry in surgical specimens may provide more accurate prognostic stratification for patients with PDAC. PMID- 27195907 TI - Myoepithelial cells in lobular carcinoma in situ: distribution and immunophenotype. AB - Myoepithelial cells have important physical and paracrine roles in breast tissue development, maintenance, and tumor suppression. Recent molecular and immunohistochemical studies have demonstrated phenotypic alterations in ductal carcinoma in situ-associated myoepithelial cells. Although the relationship of lobular carcinoma in situ (LCIS) and myoepithelial cells was described in 1980, further characterization of LCIS-associated myoepithelial cells is lacking. We stained 27 breast specimens harboring abundant LCIS with antibodies to smooth muscle myosin heavy chain, smooth muscle actin, and calponin. Dual stains for E cadherin/smooth muscle myosin heavy chain and CK7/p63 were also performed. In each case, the intensity and distribution of staining in LCIS-associated myoepithelial cells were compared with normal breast tissue on the same slide. In 78% of the cases, LCIS-associated myoepithelial cells demonstrated decreased staining intensity for one or more myoepithelial markers. The normal localization of myoepithelial cells (flat against the basement membrane, pattern N) was seen in 96% of LCIS, yet 85% of cases had areas with myoepithelial cell cytoplasm oriented perpendicular to the basement membrane (pattern P), and in 30% of cases, myoepithelial cells appeared focally admixed with LCIS cells (pattern C). This study characterizes detailed architectural and immunophenotypic alterations of LCIS-associated myoepithelial cells. The finding of variably diminished staining favors application of several myoepithelial immunostains in clinical practice. The interaction of LCIS with myoepithelial cells, especially in light of the perpendicular and central architectural arrangements, deserves further mechanistic investigation. PMID- 27195908 TI - Heterotopic pancreas: a clinicopathological study of 184 cases from a single high volume medical center in China. AB - Heterotopic pancreas (HP) is often an incidental finding during operative or endoscopic procedures and described in case reports and small series in the literature. Large clinicopathological studies with a systematic analysis remain lacking. Herein, we identified 184 (0.18%; 184/99 544) consecutive histology proven HP cases of 89 770 surgical resections and 9774 upper endoscopic biopsies carried out at a single medical center in China. Each case was diagnosed by unequivocal identification of pancreatic acini at a location outside the pancreas. The patients' median age was 49 years (range, 14-82) with a slight female predominance (male/female ratio, 0.94). Clinical presentation at diagnosis was nonspecific. Preoperatively, most (54.9%; 101/184) HP lesions were misdiagnosed. Only 26 HP lesions (14.1%) were correctly diagnosed, all in the stomach except for 1 in the duodenum; 57 (31%) were detected during operative procedures for other conditions. The most frequent location of HP was, in descending order, the stomach (97; 52.7%), small intestine (48; 26%), lesser and greater curvature omentum (18; 10%), spleen and hilar region (5; 2.7%), porta hepatis (2; 1%), gallbladder (1; 0.5%), peridistal esophageal tissue (4; 2.2%), and mesentery (7; 3.8%). The size of HP varied from smaller than 0.5 cm (35.3%), 0.6 to 1 cm (34.8%), to larger than 1.1 cm (29.9%). Because of difficulty in preoperative diagnosis, careful workup for upper gastrointestinal diseases with HP as a differential diagnosis may increase the chance of accurate diagnosis and appropriate patient management. PMID- 27195909 TI - The new "ethics" regulations and the "law of unintended consequences". PMID- 27195911 TI - An overview of multiphase cartilage mechanical modelling and its role in understanding function and pathology. AB - There is a long history of mathematical and computational modelling with the objective of understanding the mechanisms governing cartilage's remarkable mechanical performance. Nonetheless, despite sophisticated modelling development, simulations of cartilage have consistently lagged behind structural knowledge and thus the relationship between structure and function in cartilage is not fully understood. However, in the most recent generation of studies, there is an emerging confluence between our structural knowledge and the structure represented in cartilage modelling. This raises the prospect of further refinement in our understanding of cartilage function and also the initiation of an engineering-level understanding for how structural degradation and ageing relates to cartilage dysfunction and pathology, as well as informing the potential design of prospective interventions. Aimed at researchers entering the field of cartilage modelling, we thus review the basic principles of cartilage models, discussing the underlying physics and assumptions in relatively simple settings, whilst presenting the derivation of relatively parsimonious multiphase cartilage models consistent with our discussions. We proceed to consider modern developments that start aligning the structure captured in the models with observed complexities. This emphasises the challenges associated with constitutive relations, boundary conditions, parameter estimation and validation in cartilage modelling programmes. Consequently, we further detail how both experimental interrogations and modelling developments can be utilised to investigate and reduce such difficulties before summarising how cartilage modelling initiatives may improve our understanding of cartilage ageing, pathology and intervention. PMID- 27195910 TI - PCSK9 Inhibition With Monoclonal Antibodies: Modern Management of Hypercholesterolemia. AB - Current guidelines for hypercholesterolemia treatment emphasize lifestyle modification and lipid-modifying therapy to reduce the risk for cardiovascular disease. Statins are the primary class of agents used for the treatment of hypercholesterolemia. Although statins are effective for many patients, they fail to achieve optimal reduction in lipids for some patients, including those who have or are at high risk for cardiovascular disease. The PCSK9 gene was identified in the past decade as a potential therapeutic target for the management of patients with hypercholesterolemia. Pharmacologic interventions to decrease PCSK9 levels are in development, with the most promising approach using monoclonal antibodies that bind to PCSK9 in the plasma. Two monoclonal antibodies, alirocumab and evolocumab, have recently been approved for the treatment of hypercholesterolemia, and a third one, bococizumab, is in phase 3 clinical development. All 3 agents achieve significant reductions in levels of low-density lipoprotein cholesterol, as well as reductions in non-high-density lipoprotein cholesterol, apolipoprotein B, and lipoprotein(a). Long-term outcome trials are under way to determine the sustained efficacy, safety, and tolerability of PCSK9 inhibitors and whether this novel class of agents decreases the risk for major cardiovascular events in patients on lipid-modifying therapy. Available data suggest that PCSK9 inhibitors provide a robust reduction in atherogenic cholesterol levels with a good safety profile, especially for patients who fail to obtain an optimal clinical response to statin therapy, those who are statin intolerant or have contraindications to statin therapy, and those with familial hypercholesterolemia. PMID- 27195914 TI - Production of the Fusarium Mycotoxin Moniliformin by Penicillium melanoconidium. AB - Moniliformin is a mycotoxin produced by several cereal associated Fusaria. Here, we show for the first time that moniliformin can be produced by the cereal fungus, Penicillium melanoconidium (4 out of 4 strains), but not in the related species in the Viridicata series. Moniliformin was detected in 10 out of 11 media: two agars and several cereal and bean types. Moniliformin was identified by a novel mixed-mode anionic exchange reversed phase chromatographic method which was coupled to both tandem mass spectrometry (MS) and high resolution MS. Mixed-mode chromatography showed superior peak shape compared to that of HILIC and less matrix interference compared to that of reversed phase chromatography, but during a large series of analyses, the column was fouled by matrix interferences. Wheat and beans were artificially infected by P. melanoconidium containing up to 64 and 11 mg/kg moniliformin, respectively, while penicillic acid, roquefortine C, and penitrem A levels in wheat were up to 1095, 38, and 119 mg/kg, respectively. PMID- 27195913 TI - Dasatinib promotes paclitaxel-induced necroptosis in lung adenocarcinoma with phosphorylated caspase-8 by c-Src. AB - Cisplatin and paclitaxel are considered to be the backbone of chemotherapy in lung adenocarcinoma. These agents show pleiotropic effects on cell death. However, the precise mechanisms remain unclear. The present study reported that phosphorylated caspase-8 at tyrosine 380 (p-Casp8) was characterized as a biomarker of chemoresistance to TP regimen (cisplatin and paclitaxel) in patients with resectable lung adenocarcinoma with significantly poorer 5-year disease-free survival (DFS) and overall survival (OS). Cisplatin killed lung adenocarcinoma cells regardless of c-Src-induced caspase-8 phosphorylation at tyrosine 380. Subsequently, we identified a novel mechanism by which paclitaxel induced necroptosis in lung adenocarcinoma cells that was dependent upon p-Casp8, receptor-interacting protein kinase 1 (RIPK1), and RIPK3. Moreover, dasatinib, a c-Src inhibitor, dephosphorylated caspase-8 to facilitate necroptosis, rather than apoptosis, in paclitaxel-treated p-Casp8-expressing lung adenocarcinoma cells. The data from our study revealed previously unrecognized roles of p-Casp8 as a positive effector in the initiation of necroptosis and as a negative effector in the repression of the interaction between RIPK1 and RIPK3. Moreover, these outcomes supported the need for further clinical studies with the goal of evaluating the efficacy of dasatinib plus paclitaxel in the treatment of lung adenocarcinoma. PMID- 27195915 TI - Graphene-Rhodamine Nanoprobe for Colorimetric and Fluorimetric Hg(2+) Ion Assay. AB - This article reveals the first ever prospective application of Graphene-Rhodamine array (GRH) as a colorimetric and fluorimetric sensor for Hg(2+) ions. The duality of Graphene to undergo pi-pi and dispersive interactions with Rhodamine as well as to act as a selective adsorbent for Hg(2+) is conceptualized in this study. These interactions lead to decrease in absorbance of the dye in the presence of graphene, which is restored when kept in contact with Hg(2+) ions. The feasibility of the mechanism has been proved using EDTA as the coordinating ligand. It is noteworthy that all the optical variations occurred in the visible scale of the electromagnetic spectrum. The GRH array exhibited higher sensitivity toward the target ion with a limit of detection of 2 ppb. A perfect linear variation of absorbance at 554 nm with Hg(2+) concentration was observed in 0 1000 nM range, enabling the use of the system as a quantitative sensor for the test ion. The commendable selectivity of the array toward Hg(2+) ion has been investigated by observing the optical response in the presence of other environmentally relevant metal ions. A reversible turn off and turn on INHIBIT logic gate has been proposed which extends the scope of the designed array for the development of automated chemical systems. The fluorescence resonance energy transfer (FRET) ability of graphene paves the backbone for the fluorimetric detection. Fluorimetric strategy yielded a much lower limit of detection of 380 ppt using this probe, which makes a significant advance in trace detection of Hg(2+) ions. PMID- 27195912 TI - Molecular imaging to guide systemic cancer therapy: Illustrative examples of PET imaging cancer biomarkers. AB - Molecular imaging agents have the ability to non-invasively visualize, characterize, and quantify the molecular biology of disease. Recent advances in nuclear probe development, particularly in PET radiotracers, have generated many new imaging agents with precise molecular targets. With such specificity, PET probes may be utilized as biomarkers to objectively interrogate and evaluate pathology. Whereas the current indications for PET imaging are predominately confined to staging and restaging of malignancy, the utility of PET greatly expands when utilized as a biomarker, the topic of this review. As an imaging biomarker, PET may be used to (1) measure target expression to select subsets of patients who would most benefit from targeted therapy; (2) measure early treatment response to predict therapeutic efficacy; and (3) relate tumor response to survival. This review will discuss the application of radiotracers to targeted cancer therapy. Particular attention is given to new radiotracers evaluated in recently completed clinical trials and those with current or potential clinical utility. The diverse roles of PET in clinical trails for drug development are also examined. PMID- 27195916 TI - Boost Your Body: Self-Improvement Magazine Messages Increase Body Satisfaction in Young Adults. AB - The verbal messages that contextualize exposure to idealized body imagery may moderate media users' body satisfaction. Such contextualizing verbal messages often take the form of social comparison motives in fashion magazines, while body dissatisfaction is an important mechanism underlying various body image-related health issues like depression and unbalanced weight status. Hence, the present study applied social comparison motives as induced through magazine cover messages. Hypotheses were tested in an experimental design with social comparison motives (self-improvement vs. self-evaluation vs. control) and recipient gender as between-subjects factors and body satisfaction as within-subjects factor (N = 150). Results showed that self-improvement messages accompanying ideal body media models increased body satisfaction, compared to control messages and baseline measures. In contrast, the self-evaluation messages did not impact body satisfaction. Results imply that inconsistencies regarding effects from exposure to idealized body imagery are explained by the context in which media images are portrayed, evoking differential social comparison motives. Moreover, the findings imply that health communication interventions can use verbal messages on body improvement as helpful tools, if they draw on social comparison motives effectively. PMID- 27195917 TI - Detection of enterovirus D68 in patients hospitalised in three tertiary university hospitals in Germany, 2013 to 2014. AB - Enterovirus D68 (EV-D68) has been recognised as a worldwide emerging pathogen associated with severe respiratory symptoms since 2009. We here report EV-D68 detection in hospitalised patients with acute respiratory infection admitted to three tertiary hospitals in Germany between January 2013 and December 2014. From a total of 14,838 respiratory samples obtained during the study period, 246 (1.7%) tested enterovirus-positive and, among these, 39 (15.9%) were identified as EV-D68. Infection was observed in children and teenagers (0-19 years; n=31), the majority (n=22) being under five years-old, as well as in adults > 50 years of age (n=8). No significant difference in prevalence was observed between the 2013 and 2014 seasons. Phylogenetic analyses based on viral protein 1 (VP1) sequences showed co-circulation of different EV-D68 lineages in Germany. Sequence data encompassing the entire capsid region of the genome were analysed to gain information on amino acid changes possibly relevant for immunogenicity and revealed mutations in two recently described pleconaril binding sites. PMID- 27195918 TI - Overcoming the Fundamental Barrier Thickness Limits of Ferroelectric Tunnel Junctions through BaTiO3/SrTiO3 Composite Barriers. AB - Ferroelectric tunnel junctions (FTJs) have attracted increasing research interest as a promising candidate for nonvolatile memories. Recently, significant enhancements of tunneling electroresistance (TER) have been realized through modifications of electrode materials. However, direct control of the FTJ performance through modifying the tunneling barrier has not been adequately explored. Here, adding a new direction to FTJ research, we fabricated FTJs with BaTiO3 single barriers (SB-FTJs) and BaTiO3/SrTiO3 composite barriers (CB-FTJs) and reported a systematic study of FTJ performances by varying the barrier thicknesses and compositions. For the SB-FTJs, the TER is limited by pronounced leakage current for ultrathin barriers and extremely small tunneling current for thick barriers. For the CB-FTJs, the extra SrTiO3 barrier provides an additional degree of freedom to modulate the barrier potential and tunneling behavior. The resultant high tunability can be utilized to overcome the barrier thickness limits and enhance the overall CB-FTJ performances beyond those of SB-FTJ. Our results reveal a new paradigm to manipulate the FTJs through designing multilayer tunneling barriers with hybrid functionalities. PMID- 27195927 TI - Nurses' Time Use in Forensic Psychiatry: Core Interventions Outlined in the Finnish Clinical Practice Guideline on Schizophrenia. AB - Forensic psychiatric nurses are key in implementing the core interventions outlined in the clinical practice guideline on schizophrenia. This study endeavors to ascertain how these were implemented in routine practice in forensic psychiatry by measuring how nurses use their time. Data were collected from registered nurses and practical mental nurses in all forensic psychiatric facilities in Finland using self-report diary forms for 1 week. In total, nurses used 20% of their weekly working hours on core interventions. The differences between the nurse groups were statistically significant (p <= 0.05) regarding the following core interventions: (a) care planning with physicians, (b) pharmacotherapy, and (c) basic clinical care. Nurses' qualifications, types of facilities and units, working experience, gender, and staffing levels explained the time used on core interventions. In summary, forensic psychiatric inpatients received insufficient appropriate nursing services according to the relevant guideline regarding schizophrenia. Furthermore, managerial recommendations need to restructure nurses' time use to increase the proportion of productive working hours spent with patients. PMID- 27195926 TI - The Anatomy of Human Trafficking: Learning About the Blues: A Healthcare Provider's Guide. AB - Human trafficking is a major global public health concern. It is a grave crime that violates human rights. Contrary to healthcare providers' perceptions, victims of human trafficking come in contact with the healthcare system while being trafficked, with the emergency department being the most frequented setting for medical treatment. In this article, we explore the anatomy of human trafficking, including the scope of the problem, definitions, and types and elements of human trafficking. The roles of clinicians, particularly emergency department nurses and advanced practice nurses, in screening and identifying those at risk are examined. Clinical practice tools and guidelines that may be used by clinicians to guide the treatment of human trafficking victims are reviewed. Finally, current strategies and resources that address human trafficking are presented. For the purpose of this article, the terms "human trafficking" or "trafficking" will be used throughout. PMID- 27195928 TI - Active Shooters: What Emergency Nurses Need to Know. AB - Active shooter incidents have been on the rise in the United States in the last 2 decades, specifically events occurring in public areas traditionally considered safe such as churches, schools, and hospitals. An examination of historical events shows that the emergency department (ED) nurse must be equipped to handle any situation that may arise, including the increasing likelihood of an active shooter situation. Hospital response to these occurrences is changing, and protocols for staff response are being adjusted on a regular basis. Immediate response, postevent actions, and evidence collection procedures must be a part of the ED nurses' ongoing education. Lessons learned from events that have occurred must be examined so ED nurses can be more aware and ready to respond to the increasing chance of an event such as this occurring in their ED. PMID- 27195929 TI - Female Ex-Offender Perspectives on Drug Initiation, Relapse, and Desire to Remain Drug Free. AB - Recently released homeless women residing in temporary residential drug treatment (RDT) programs are at a critical juncture in the process of recovery, transition, and reentry. The purpose of this study was to explore factors influencing initial use of drugs and relapse triggers among a sample of incarcerated women exiting jails and prisons, residing in an RDT program, and preparing for reentry into their communities. Among this population, relapse to drug use and recidivism are common. A qualitative study was conducted utilizing focus groups to understand the perspectives of formerly incarcerated, currently homeless women residing in an RDT program. Content analysis generated the development of three broad categories: (a) factors associated with first drug use, (b) factors involved in relapse, and (c) factors influencing desire to remain drug free. A discussion follows highlighting the importance of targeted interventions at RDT sites that integrate physical, psychological, and social needs to optimize reentry into communities. This includes a focus on building self-esteem and life skills and providing access to resources such as housing, employment, and healthcare. PMID- 27195931 TI - The Anatomy of Human Trafficking: Learning About the Blues: A Healthcare Provider's Guide. PMID- 27195930 TI - Unnatural Deaths Among Children and Adolescents in Isfahan Province, Iran: A Forensic Epidemiology Study of Postmortem Data. AB - INTRODUCTION: The issue of child and adolescent injury and violence is often absent from discussions and is largely invisible in public health policies. The purpose of this study was to describe the frequency and pattern of unnatural deaths during childhood and adolescence in Isfahan province in Iran. MATERIALS AND METHODS: This retrospective, descriptive study involved unnatural deaths among individuals under the age of 20 years who died from unnatural causes as determined by a forensic autopsy at the Legal Medicine Center of Isfahan. During the study period, 8,010 unnatural deaths occurred, 1,222 of which were individuals under 20 years old. RESULTS: All 1,222 of these unnatural deaths were identified through autopsy. Among the 1,222 cases, 895 (73.2%) were male, and 327 were female (26.8%). Accidental deaths were found to be the most frequent manner of death comprising 1,029 (83.96%) cases, followed by suicide (120, 9.82%), undetermined cause of death (39, 3.19%), and homicide (9, 2.86%) cases. Road traffic accidents were the number 1 cause of death (597, 49%), followed by burns (122, 10%) and hanging (90, 7.4%). DISCUSSION: Injuries and violence that occur during childhood and adolescence represent a global public health problem, especially in low- and middle-income regions, and require urgent action. PMID- 27195932 TI - Understanding the Association between Social Capital and Self-Rated Health of South Korean Elderly with Disabilities. AB - The aim of the current study is to investigate the association between social capital and self-rated health among people who are elderly with disabilities in South Korea. For this purpose, the authors analyzed the fourth wave data of the Korean Health Panel Survey (KHPS) that included a sample of 408 people who are elderly with disabilities. The authors found that the unmet health care needs were significantly associated with self-rated health of the people who are elderly with disabilities (beta = - .286, p < .05). The authors also found that respect was significantly related to self-rated health (beta = .393, p < .05). PMID- 27195933 TI - Physical Activity and Digestive System Cancer Risk: Still Chasing the Promise. PMID- 27195934 TI - Comparative study of plant responses to carbon-based nanomaterials with different morphologies. AB - The relationship between the morphology of carbon-based nanomaterials (CBNs) and the specific response of plants exposed to CBNs has not been studied systematically. Here, we prove that CBNs with different morphologies can activate cell growth, germination, and plant growth. A tobacco cell culture growth was found to increase by 22%-46% when CBNs such as helical multi-wall carbon nanotubes (MWCNTs), few-layered graphene, long MWCNTs, and short MWCNTs were added to the growth medium at a concentration of 50 MUg ml(-1). The germination of exposed tomato seeds, as well as the growth of exposed tomato seedlings, were significantly enhanced by the addition of all tested CBNs. The presence of CBNs inside exposed seeds was confirmed by transmission electron microscopy and Raman spectroscopy. The effects of helical MWCNTs on gene expression in tomato seeds and seedlings were investigated by microarray technology and real time-PCR. Helical MWCNTs affected a number of genes involved in cellular and metabolic processes and response to stress factors. It was shown that the expression of the tomato water channel gene in tomato seeds exposed to helical MWCNTs was upregulated. These established findings demonstrate that CBNs with different morphologies can cause the same biological effects and share similar mechanisms in planta. PMID- 27195935 TI - Decline in Antigenicity of Tumor Markers by Storage Time Using Pathology Sections Cut From Tissue Microarrays: Erratum. PMID- 27195936 TI - How U.S. Doctors Die: A Cohort Study of Healthcare Use at the End of Life. AB - OBJECTIVES: To compare healthcare use in the last months of life between physicians and nonphysicians in the United States. DESIGN: A retrospective observational cohort study. SETTING: United States. PARTICIPANTS: Fee-for-service Medicare beneficiaries: decedent physicians (n = 9,947) and a random sample of Medicare decedents (n = 192,006). MEASUREMENTS: Medicare Part A claims data from 2008 to 2010 were used to measure days in the hospital and proportion using hospice in the last 6 months of life as primary outcome measures adjusted for sociodemographic characteristics and regional variations in health care. RESULTS: Inpatient hospital use in the last 6 months of life was no different between physicians and nonphysicians, although more physicians used hospice and for longer (using the hospital: odds ratio (OR) = 0.98, 95% confidence interval (CI) = 0.93-1.04; hospital days: mean difference 0.26, P = .14); dying in the hospital: OR = 0.99, 95% CI = 0.95-1.04; intensive care unit (ICU) or critical care unit (CCU) days: mean difference 0.35 more days for physicians, P < .001); using hospice: OR = 1.23, 95% CI = 1.18-1.29; number of days in hospice: mean difference 2.06, P < .001). CONCLUSION: This retrospective, observational study is subject to unmeasured confounders and variation in coding practices, but it provides preliminary evidence of actual use. U.S. physicians were more likely to use hospice and ICU- or CCU-level care. Hospitalization rates were similar. PMID- 27195937 TI - Association of Sudden Sensorineural Hearing Loss With Vertebrobasilar Insufficiency. AB - IMPORTANCE: Little is known about the association between sudden sensorineural hearing loss (SSNHL) and vertebrobasilar insufficiency (VBI). OBJECTIVE: To explore the association between SSNHL and VBI. DESIGN, SETTING, AND PARTICIPANTS: This investigation was a population-based, case-control study. Patients from January 1, 2000, to December 31, 2011, were retrospectively identified from the Taiwan National Health Insurance Research Database, which includes claims data on a random sample of 1 million people. MAIN OUTCOMES AND MEASURES: Using propensity score matching on age and sex, patients were stratified at a 1:4 ratio into a study group comprising 5304 patients with a diagnosis of SSNHL and a control group comprising 21 216 patients. Those with a diagnosis of VBI before the index date (the date each patient was diagnosed as having SSNHL) in both groups were then identified. A conditional logistic regression model was used to estimate the adjusted odds ratios (ORs) and 95% CIs as a measure of the association between SSNHL and VBI. RESULTS: The study cohort comprised 26 520 patients. Their mean (SD) age was 51.3 (17.2) years, and 47.1% (12 500 of 26 520) were female. Vertebrobasilar insufficiency was diagnosed before the index date in 0.5% (26 of 5304) of patients with SSNHL and in 0.2% (38 of 21 216) of controls without SSNHL. After adjusting for comorbid medical disorders, patients with SSNHL were more likely than controls to have had VBI (OR, 1.76; 95% CI, 1.02-3.04). There were no significant differences in the prevalence of VBI among male patients with SSNHL vs male controls (OR, 1.72; 95% CI, 0.87-3.40) or among female patients with SSNHL vs female controls (OR, 1.86; 95% CI, 0.76-4.59). CONCLUSIONS AND RELEVANCE: Patients with VBI appear to be at increased risk of developing SSNHL. Further research is needed to investigate the association among the severity of VBI, the risk of SSNHL, and the pattern of the audiometric curve. PMID- 27195938 TI - Involvement of FST1 from Fusarium verticillioides in virulence and transport of inositol. AB - Fumonisin B1 (FB1), a polyketide mycotoxin produced by Fusarium verticillioides during the colonization of maize kernels, is detrimental to human and animal health. FST1 encodes a putative protein with 12 transmembrane domains; however, its function remains unknown. The FST1 gene is highly expressed by the fungus in the endosperm of maize kernels compared with the levels of expression in germ tissues. Previous research has shown that FST1 affects FB1 production, virulence, hydrogen peroxide resistance, hydrophobicity and macroconidia production. Here, we examine the phylogeny of FST1, its expression in a Saccharomyces cerevisiae strain lacking a functional myo-inositol transporter (ITR1) and the effect of amino acid changes in the central loop and C-terminus regions of FST1 on functionality. The results indicate that expression of FST1 in an ITR1 mutant strain restores growth on myo-inositol medium to wild-type levels and restores the inhibitory effects of FB1, suggesting that FST1 can transport both myo inositol and FB1 into yeast cells. Our results with engineered FST1 also indicate that amino acids in the central loop and C-terminus regions are important for FST1 functionality in both S. cerevisiae and F. verticillioides. Overall, this research has established the first characterized inositol transporter in filamentous fungi and has advanced our knowledge about the global regulatory functions of FST1. PMID- 27195939 TI - An examination of the roles of trauma exposure and posttraumatic stress disorder on emotion regulation strategies of Operation Iraqi Freedom, Operation Enduring Freedom, and Operation New Dawn veterans. AB - Theories of posttraumatic stress disorder (PTSD) implicate emotional processes, including difficulties utilizing adaptive emotion regulation strategies, as critical to the etiology and maintenance of PTSD. Operation Iraqi Freedom, Operation Enduring Freedom, and Operation New Dawn (OIF/OEF/OND) veterans report high levels of combat exposure and PTSD. We aimed to extend findings suggesting that emotion regulation difficulties are a function of PTSD, rather than combat trauma exposure or common comorbidities, to OIF/OEF/OND veterans, in order to inform models of PTSD risk and recovery that can be applied to returning veterans. We tested differences in emotion regulation, measured with the Difficulties in Emotion Regulation Scale and Emotion Regulation Questionnaire, among trauma-exposed veterans with (n = 24) or without PTSD (n = 22) and healthy civilian comparison participants (n = 27) using multivariate analyses of covariance, adjusting for major depressive disorder, anxiety disorders, and demographic variables (age, sex, and ethnicity). Veterans with PTSD reported more use of expressive suppression and more difficulties with emotion regulation than veterans without PTSD and healthy comparison participants. Groups did not differ on cognitive reappraisal. Findings suggest the key role of PTSD above and beyond trauma exposure, depression, and anxiety in specific aspects of emotion dysregulation among OIF/OEF/OND veterans. Interventions that help veterans expand and diversify their emotion regulation skills may serve as helpful adjunctive treatments for PTSD among OIF/OEF/OND veterans. PMID- 27195941 TI - Determination of Gluten in Processed and Nonprocessed Corn Products by Qualitative R5 Immunochromatographic Dipstick: Collaborative Study, First Action 2015.16. AB - In September 2013, the AACC International (AACI) Protein Technical Committee (now Protein and Enzymes Technical Committee) initiated a collaborative study of a method for the qualitative analysis of intact gluten in processed and nonprocessed corn products, using an R5 immunochromatographic dipstick system. It was validated to demonstrate that potential gluten-free products contain gluten lower than the Codex threshold of 20 mg/kg gluten. The results of the collaborative test with 18 participants confirmed that the method is suitable to detect gluten contaminations that are clearly lower than the threshold. It is recommended that the method be accepted by AOAC as Official First Action. PMID- 27195940 TI - Clinical evaluation of salivary carbohydrate antigen 125 and leptin in controls and parotid tumours. AB - OBJECTIVES: We determined the correlation between saliva and serum for CA125 and leptin, and evaluated their clinical screening potential for parotid tumours. SUBJECTS AND METHODS: Serum, acid-stimulated bilateral parotid saliva and chewing stimulated whole saliva were collected and measured the levels of CA125 and leptin with electrochemiluminescence immunoassay and enzyme-linked immunosorbent assay for healthy controls and patients with unilateral parotid tumour. Intra- and intergroup comparisons were made among them. Correlations and receiver operating curve analyses were also conducted. RESULTS: There was no correlation between salivary and serum CA125 (r = -0.157-0.265, P > 0.05), while significant correlation was found for leptin (r = 0.219-0.761, P < 0.05). Leptin levels in tumour parotid saliva and CA125 levels in whole saliva were elevated significantly (P < 0.001) and showed screening potential for parotid tumours. Salivary and serum leptin levels were significantly higher in women than in men (P < 0.001). CONCLUSIONS: Salivary CA125 might originate primarily from salivary gland and tumour rather than from blood, while salivary leptin might originate from both blood and salivary gland. Multiple sources might contribute to the significantly elevated CA125 in whole saliva. Whole saliva CA125 and parotid saliva leptin reflected the occurrence of parotid tumours, while serum CA125 and leptin did not. Salivary CA125 and leptin could not distinguish malignant parotid tumours. When detecting leptin level, the influence of subjects' sex must be considered. PMID- 27195943 TI - The Correlation of Endoscopic Findings and Clinical Features in Korean Patients with Scrub Typhus: A Cohort Study. AB - Scrub typhus is an infectious disease caused by Orientia tsutsugamushi-induced systemic vasculitis, but the involvement of the gastrointestinal tract and the endoscopic findings associated with scrub typhus are not well understood. We performed a prospective study and recommend performing esophagogastroduodenoscopy (EGD) for all possible scrub typhus patients, regardless of gastrointestinal symptoms. Gastrointestinal symptoms, endoscopic findings and clinical severity based on organ involvement and ICU admission were analyzed. Gastrointestinal symptoms occurred in up to 76.4% of scrub typhus patients. The major endoscopic findings were ulcers (43/127, 33.9%). Interestingly, 7.1% (9/127) of the patients presented with esophageal candidiasis. There was no correlation between the presence or absence of gastrointestinal symptoms and the endoscopic grade (P = 0.995). However, there was a positive correlation between the clinical severity and the endoscopic findings (P = 0.001). Sixty-three percent of the patients presented with erosion or ulcers on prospectively performed endoscopic evaluations, irrespective of gastrointestinal symptoms. Gastrointestinal symptoms did not reflect the need for endoscopy. Scrub typhus patients could have significant endoscopic abnormalities even in the absence of gastrointestinal symptoms. PMID- 27195942 TI - Resting state morphology predicts the effect of theta burst stimulation in false belief reasoning. AB - When required to represent a perspective that conflicts with one's own, functional magnetic resonance imaging (fMRI) suggests that the right ventrolateral prefrontal cortex (rvlPFC) supports the inhibition of that conflicting self-perspective. The present task dissociated inhibition of self perspective from other executive control processes by contrasting belief reasoning-a cognitive state where the presence of conflicting perspectives was manipulated-with a conative desire state wherein no systematic conflict existed. Linear modeling was used to examine the effect of continuous theta burst stimulation (cTBS) to rvlPFC on participants' reaction times in belief and desire reasoning. It was anticipated that cTBS applied to rvlPFC would affect belief but not desire reasoning, by modulating activity in the Ventral Attention System (VAS). We further anticipated that this effect would be mediated by functional connectivity within this network, which was identified using resting state fMRI and an unbiased model-free approach. Simple reaction-time analysis failed to detect an effect of cTBS. However, by additionally modeling individual measures from within the stimulated network, the hypothesized effect of cTBS to belief (but, importantly, not desire) reasoning was demonstrated. Structural morphology within the stimulated region, rvlPFC, and right temporoparietal junction were demonstrated to underlie this effect. These data provide evidence that inconsistencies found with cTBS can be mediated by the composition of the functional network that is being stimulated. We suggest that the common claim that this network constitutes the VAS explains the effect of cTBS to this network on false belief reasoning. Hum Brain Mapp 37:3502-3514, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27195944 TI - How to determine cardiac ion channels targeted by drugs using the isolated rabbit ventricular wedge model. AB - INTRODUCTION: The rabbit left ventricular wedge (RLVW) has been demonstrated as a highly sensitive and specific preclinical model in assessing drug-induced QT prolongation and proarrhythmias. However, there is a need to determine drugs' cardiac ion channel profiles beyond QT measurement. In this study, we present an approach to determine cardiac ion channels targeted by drugs with analyzing a few key ECG parameters plus a contractility parameter obtained from the RLVW. METHODS: The RLVW assay was used for testing 18 drugs with well-known ion channel profiles. A transmural ECG and isometric contractility were recorded. Five parameters including QRS, QT, Tp-e/QT ratio, QT-BCL slope and the positive staircase response of contractility were analyzed. RESULTS: There were distinguished drug-induced ECG and contractility changes from which targeted cardiac ion channels by drugs could be determined. Inhibition of sodium channel resulted in rate-dependent QRS widening, QT and Tp-e shortening and a reduced QT BCL slope. Although both IKr and IKs blockers prolonged QT interval, IKr blockers but not IKs increased Tp-e/QT ratio. Both potassium channel openers and calcium channel blockers markedly shortened QT and Tp-e intervals, but only calcium channel blockers could reverse the positive staircase response of contractility. DISCUSSION: The results in the present study are correlated closely to the drugs' well-known clinical profiles. This indicates that the RLVW assay with an adequate experimental protocol plus analysis of 5 key parameters is highly valuable in preclinical assessment of drug candidates for their detailed ion channel activities, proarrhythmic risks and other adverse effects. The limitations of the RLVW assay are also addressed. PMID- 27195945 TI - Unlock the information in your data: Software to find, classify, and report on data patterns and arrhythmias. AB - INTRODUCTION: Safety studies generate a significant volume of waveform and calculated data. The verification of calculated data and the process of searching through these data for patterns of interest (including arrhythmias) is time intensive. Data InsightsTM has been developed for the PonemahTM software platform to provide efficient verification and search capabilities. METHODS: Searches may be constructed using calculated and pattern matching data available in Ponemah. Searches are composed of one or more search clauses that may be combined using Boolean operators (AND, OR). Each search clause is a Boolean expression composed of inputs and functions. Data Insights includes a number of predefined species specific searches for arrhythmias that were qualified for canine, non-human primate and minipigs. Qualification compared arrhythmias identified using Data Insights against a board-certified veterinary cardiologist hand-scored reference datasets. RESULTS: In seven out of eight arrhythmia types, arrhythmia incidences identified by Data Insights were congruent to those identified by hand-scoring. Premature Atrial Contractions (PACs) accounted for the only discrepancy in hand scored data-segments, although all overt PACs identified by the veterinary cardiologist were also identified by Data Insights. Unscored atrio-ventricular blocks accounted for the remaining differences. DISCUSSION: Data Insights may be used to support different applications, as searches may be created for any physiologic signal type. Its interactive dialog permits rapid review of search results and a dynamic method for handling outliers, signal noise, and false positives. Data Insights provides an efficient method to locate, present, and report on data patterns and anomalies for accurate, consistent results. PMID- 27195946 TI - Molecular recognition between insulin and dextran encapsulated gold nanoparticles. AB - Insulin is a peptide hormone that can regulate the metabolism of carbohydrates and lipids. This hormone is closely related to glucose-uptake in cells and can control blood glucose levels. Dextran is a polysaccharide composed of glucose units. In this study, we discovered that dextran-encapsulated gold nanoparticles (AuNPs@Dextran) and nanoclusters (AuNCs@Dextran) can be used to recognize insulin. The dissociation constant of insulin toward AuNPs@Dextran was estimated to be ~5.3 * 10-6 M. The binding site on insulin toward the dextran on the nanoprobes was explored as well. It was found that the sequence of numbers 1-22 on the insulin B chain can interact with the dextran encapsulated nanoprobes. Additionally, we also demonstrated that the dextran-encapsulated nanoprobes could be used as concentration probes to selectively enrich trace amounts of insulin (~1 pM) from serum samples. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27195948 TI - Usage Trends of Open Access and Local Journals: A Korean Case Study. AB - Articles from open access and local journals are important resources for research in Korea and the usage trends of these articles are important indicators for the assessment of the current research practice. We analyzed an institutional collection of published papers from 1998 to 2014 authored by researchers from Seoul National University, and their references from papers published between 1998 and 2011. The published papers were collected from Web of Science or Scopus and were analyzed according to the proportion of articles from open access journals. Their cited references from published papers in Web of Science were analyzed according to the proportion of local (South Korean) or open access journals. The proportion of open access papers was relatively stable until 2006 (2.5 ~ 5.2% in Web of Science and 2.7 ~ 4.2% in Scopus), but then increased to 15.9% (Web of Science) or 18.5% (Scopus) in 2014. We analyzed 2,750,485 cited references from 52,295 published papers. We found that the overall proportion of cited articles from local journals was 1.8% and that for open access journals was 3.0%. Citations of open access articles have increased since 2006 to 4.1% in 2011, although the increase in open access article citations was less than for open access publications. The proportion of citations from local journals was even lower. We think that the publishing / citing mismatch is a term to describe this difference, which is an issue at Seoul National University, where the number of published papers at open access or local journals is increasing but the number of citations is not. The cause of this discrepancy is multi-factorial but the governmental / institutional policies, social / cultural issues and authors' citing behaviors will explain the mismatch. However, additional measures are also necessary, such as the development of an institutional citation database and improved search capabilities with respect to local and open access documents. PMID- 27195947 TI - Tinnitus and hyperacusis therapy in a UK National Health Service audiology department: Patients' evaluations of the effectiveness of treatments. AB - OBJECTIVE: To assess patients' judgements of the effectiveness of the tinnitus and hyperacusis therapies offered in a specialist UK National Health Service audiology department. DESIGN: Cross-sectional service evaluation questionnaire survey. Patients were asked to rank the effectiveness of the treatment they received on a scale from 1 to 5 (1 = no effect, 5 = very effective). STUDY SAMPLE: The questionnaire was sent to all patients who received treatment between January and March 2014 (n = 200) and 92 questionnaires were returned. RESULTS: The mean score was greatest for counselling (Mean = 4.7, SD = 0.6), followed by education (Mean = 4.5, SD = 0.8), cognitive behavioural therapy - CBT (Mean = 4.4, SD = 0.7), and hearing tests (Mean = 4.4, SD = 0.9). Only 6% of responders rated counselling as 3 or below. In contrast, bedside sound generators, hearing aids, and wideband noise generators were rated as 3 or below by 25%, 36%, and 47% of participants, respectively. CONCLUSION: The most effective components of the tinnitus and hyperacusis therapy interventions were judged by the patients to be counselling, education, and CBT. PMID- 27195949 TI - Antidiabetic medications in patients with heart failure. AB - Diabetes mellitus increases the mortality secondary to heart failure independent of hypertension and coronary artery disease. Several hypoglycemic agents are used to achieve glycemic control, of which several classes however still raise controversies in terms of safety in patients with concomitant heart failure: Metformin does not carry an increased risk of exacerbation in patients with stable heart failure, yet should be avoided in patients with unstable disease or chronic kidney disease. Sulfonylureas are neither associated with an increased mortality, nor do they seem to have deleterious effects on heart failure. Thiazolidinediones are relatively contraindicated in patients with New York Heart Association class III or IV disease secondary to concerns of fluid retention and heart failure exacerbation. Glucagon-like peptide 1 agonists have shown trends towards improvement of heart failure parameters. Dipeptidylpeptidase 4 inhibitors show an overall neutral outcome, although saxagliptin can possibly be associated with an increased risk of hospitalization for heart failure. The use of sodium glucose co-transporter 2 inhibitors is associated with beneficial cardiovascular outcomes, and further studies are underway. PMID- 27195950 TI - Solid oxide membrane-assisted controllable electrolytic fabrication of metal carbides in molten salt. AB - Silicon carbide (SiC), titanium carbide (TiC), zirconium carbide (ZrC), and tantalum carbide (TaC) have been electrochemically produced directly from their corresponding stoichiometric metal oxides/carbon (MOx/C) precursors by electrodeoxidation in molten calcium chloride (CaCl2). An assembled yttria stabilized zirconia solid oxide membrane (SOM)-based anode was employed to control the electrodeoxidation process. The SOM-assisted controllable electrochemical process was carried out in molten CaCl2 at 1000 degrees C with a potential of 3.5 to 4.0 V. The reaction mechanism of the electrochemical production process and the characteristics of these produced metal carbides (MCs) were systematically investigated. X-ray diffraction, scanning electron microscopy, and transmission electron microscopy analyses clearly identify that SiC, TiC, ZrC, and TaC carbides can be facilely fabricated. SiC carbide can be controlled to form a homogeneous nanowire structure, while the morphologies of TiC, ZrC, and TaC carbides exhibit porous nodular structures with micro/nanoscale particles. The complex chemical/electrochemical reaction processes including the compounding, electrodeoxidation, dissolution-electrodeposition, and in situ carbonization processes in molten CaCl2 are also discussed. The present results preliminarily demonstrate that the molten salt-based SOM-assisted electrodeoxidation process has the potential to be used for the facile and controllable electrodeoxidation of MOx/C precursors to micro/nanostructured MCs, which can potentially be used for various applications. PMID- 27195952 TI - Multilevel Weighted Support Vector Machine for Classification on Healthcare Data with Missing Values. AB - This work is motivated by the needs of predictive analytics on healthcare data as represented by Electronic Medical Records. Such data is invariably problematic: noisy, with missing entries, with imbalance in classes of interests, leading to serious bias in predictive modeling. Since standard data mining methods often produce poor performance measures, we argue for development of specialized techniques of data-preprocessing and classification. In this paper, we propose a new method to simultaneously classify large datasets and reduce the effects of missing values. It is based on a multilevel framework of the cost-sensitive SVM and the expected maximization imputation method for missing values, which relies on iterated regression analyses. We compare classification results of multilevel SVM-based algorithms on public benchmark datasets with imbalanced classes and missing values as well as real data in health applications, and show that our multilevel SVM-based method produces fast, and more accurate and robust classification results. PMID- 27195951 TI - New 4-Acyl-1-phenylaminocarbonyl-2-phenylpiperazine Derivatives as Potential Inhibitors of Adenovirus Infection. Synthesis, Biological Evaluation, and Structure-activity Relationships. AB - The search for human adenovirus (HAdV)-specific antiviral drugs for the treatment of HAdV infections in immunocompromised patients continues to be a challenging goal for medicinal chemistry. Here, we report the synthesis, biological evaluation, and structure-activity relationships of a small molecules library. We have identified six phenylpiperazine derivatives that significantly inhibited HAdV infection. These six compounds showed the capacity to block HAdV and, in addition, human cytomegalovirus (HCMV) replications at low micromolar concentration, with little or no cytotoxicity. On the basis of our biological studies, these molecules block HAdV and HCMV infections in different phases of their life cycle, providing potential candidates for the development of a new family of antiviral drugs for the treatment of infections by DNA viruses. PMID- 27195953 TI - Correction: Emerging Role of the Calcium-Activated, Small Conductance, SK3 K+ Channel in Distal Tubule Function: Regulation by TRPV4. AB - [This corrects the article DOI: 10.1371/journal.pone.0095149.]. PMID- 27195954 TI - Toward a Common Secure Future: Four Global Commissions in the Wake of Ebola. AB - Lawrence Gostin and colleagues offer a set of priorities for global health preparedness and response for future infectious disease threats. PMID- 27195955 TI - Magnetoreception Regulates Male Courtship Activity in Drosophila. AB - The possible neurological and biophysical effects of magnetic fields on animals is an area of active study. Here, we report that courtship activity of male Drosophila increases in a magnetic field and that this effect is regulated by the blue light-dependent photoreceptor cryptochrome (CRY). Naive male flies exhibited significantly increased courtship activities when they were exposed to a >= 20 Gauss static magnetic field, compared with their behavior in the natural environment (0 Gauss). CRY-deficient flies, cryb and crym, did not show an increased courtship index in a magnetic field. RNAi-mediated knockdown of cry in cry-GAL4-positive neurons disrupted the increased male courtship activity in a magnetic field. Genetically expressing cry under the control of cry-GAL4 in the CRY-deficient flies restored the increase in male courtship index that occurred in a magnetic field. Interestingly, artificially activating cry-GAL4-expressing neurons, which include large ventral lateral neurons and small ventral lateral neurons, via expression of thermosensitive cation channel dTrpA1, also increased the male courtship index. This enhancement was abolished by the addition of the cry-GAL80 transgene. Our results highlight the phenomenon of increased male courtship activity caused by a magnetic field through CRY-dependent magnetic sensation in CRY expression neurons in Drosophila. PMID- 27195956 TI - A Comparison of the Diabetes Risk Score in HIV/AIDS Patients on Highly Active Antiretroviral Therapy (HAART) and HAART-Naive Patients at the Limbe Regional Hospital, Cameroon. AB - BACKGROUND: Highly active antiretroviral therapy (HAART) has been associated with dysglycaemia. However, there is scarce data on the risk of developing diabetes mellitus (DM) in HIV/AIDS patients in Africa. OBJECTIVES: Primarily to quantify and compare the risk of having diabetes mellitus in HIV/AIDS patients on HAART and HAART-naive patients in Limbe, Cameroon; and secondarily to determine if there is an association between HAART and increased DM risk. METHODS: A cross sectional study was conducted at the Limbe Regional Hospital HIV treatment center between April and June 2013, involving 200 HIV/AIDS patients (100 on first-line HAART regimens for at least 12 months matched by age and gender to 100 HAART naive patients). The Diabetes Risk Score (DRS) was calculated using a clinically validated model based on routinely recorded primary care parameters. A DRS >= 7% was considered as indicative of an increased risk of developing DM. RESULTS: The median DRS was significantly higher in patients on HAART (2.30%) than in HAART naive patients (1.62%), p = 0.002. The prevalence of the increased DM risk (DRS >= 7%) was significantly higher in patients on HAART, 31% (95% CI: 22.13-41.03) than in HAART-naive patients, 17% (95% CI: 10.23-25.82), p = 0.020. HAART was significantly associated with an increased DM risk, the odds ratio of the HAART group compared to the HAART-naive group was 2.19 (95% CI: 1.12-4.30, p = 0.020). However, no association was found after adjusting for BMI-defined overweight, hypertension, age, sex, family history of DM and smoking (Odds ratio = 1.22, 95% CI: 0.42-3.59, p = 0.708). Higher BMI and hypertension accounted for the increased risk of DM in patients on HAART. Also, more than 82% of the participants were receiving or had ever used Zidovudine based HAART regimens. CONCLUSION: HIV/AIDS patients on HAART could be at a greater risk of having DM than HAART-naive patients as a result of the effect of HAART on risk factors of DM such as BMI and blood pressure. PMID- 27195959 TI - The Impact of Culture on Breastfeeding Rates. PMID- 27195957 TI - Household HIV Testing Uptake among Contacts of TB Patients in South Africa. AB - BACKGROUND: In high HIV prevalence settings, offering HIV testing may be a reasonable part of contact tracing of index tuberculosis (TB) patients. We evaluated the uptake of HIV counselling and testing (HCT) among household contacts of index TB patients and the proportion of newly diagnosed HIV-infected persons linked into care as part of a household TB contact tracing study. METHODS: We recruited index TB patients at public health clinics in two South African provinces to obtain consent for household contact tracing. During scheduled household visits we offered TB symptom screening to all household members and HCT to individuals >=14years of age. Factors associated with HCT uptake were investigated using a random effects logistic regression model. RESULTS & DISCUSSION: Out of 1,887 listed household members >=14 years old, 984 (52%) were available during a household visit and offered HCT of which 108 (11%) self-reported being HIV infected and did not undergo HCT. Of the remaining 876, a total of 304 agreed to HCT (35%); 26 (8.6%) were newly diagnosed as HIV positive. In multivariable analysis, factors associated with uptake of HCT were prior testing (odds ratio 1.6; 95% confidence interval [CI]: 1.1-2.3) and another member in the household testing (odds ratio 2.4; 95% CI: 1.7-3.4). Within 3 months of testing HIV-positive, 35% reported initiating HIV care. CONCLUSION: HCT as a component of household TB contact tracing reached individuals without prior HIV testing, however uptake of HIV testing was poor. Strategies to improve HIV testing in household contacts should be evaluated. PMID- 27195958 TI - WNT7A Regulation by miR-15b in Ovarian Cancer. AB - WNT signaling is well known to play an important role in the regulation of development, cell proliferation and cell differentiation in a wide variety of normal and cancerous tissues. Despite the wealth of knowledge concerning when and where various WNT genes are expressed and downstream events under their control, there is surprisingly little published evidence of how they are regulated. We have recently reported that aberrant WNT7A is observed in serous ovarian carcinomas, and WNT7A is the sole ligand accelerating ovarian tumor progression through CTNNB1 (beta-catenin)/TCF signaling in the absence of CTNNB1 mutations. In the present study, we report that WNT7A is a direct target of miR-15b in ovarian cancer. We showed that a luciferase reporter containing the putative binding site of miR-15b in the WNT7A 3'-UTR was significantly repressed by miR 15b. Mutation of the putative binding site of miR-15b in the WNT7A 3'-UTR restored luciferase activity. Furthermore, miR-15b was able to repress increased levels of TOPFLASH activity by WNT7A, but not those induced by S33Y. Additionally, miR-15b dose-dependently decreased WNT7A expression. When we evaluated the prognostic impact of WNT7A and miR-15b expression using TCGA datasets, a significant inverse correlation in which high-expression of WNT7A and low-expression of miR-15b was associated with reduced survival rates of ovarian cancer patients. Treatment with decitabine dose-dependently increased miR-15b expression, and silencing of DNMT1 significantly increased miR-15b expression. These results suggest that WNT7A is post-transcriptionally regulated by miR-15b, which could be down-regulated by promoter hypermethylation, potentially via DNMT1, in ovarian cancer. PMID- 27195961 TI - Equilibrium between 5- and 6-Fold Coordination in the First Hydration Shell of Cu(II). AB - The hydration structure dynamics of Cu(II) ion is characterized by a combination of classical molecular dynamics simulation and X-ray absorption near-edge spectroscopy. Previous experimental data have been analyzed on the basis of 5- or 6-fold first hydration structure, with a quite well-established equatorial structure. This 4-fold equatorial geometry has been our starting point to develop a simple but effective in silico model, which provides ab initio theoretical X ray absorption spectra in very good agreement with the experimental data. Our results point out two equally populated 6- and 5-fold hydration structures with remarkable different water residence times of 5 and 98 ps, respectively, and a low free energy barrier between first and second hydration shell. PMID- 27195960 TI - Large-Scale Gene Relocations following an Ancient Genome Triplication Associated with the Diversification of Core Eudicots. AB - Different modes of gene duplication including whole-genome duplication (WGD), and tandem, proximal and dispersed duplications are widespread in angiosperm genomes. Small-scale, stochastic gene relocations and transposed gene duplications are widely accepted to be the primary mechanisms for the creation of dispersed duplicates. However, here we show that most surviving ancient dispersed duplicates in core eudicots originated from large-scale gene relocations within a narrow window of time following a genome triplication (gamma) event that occurred in the stem lineage of core eudicots. We name these surviving ancient dispersed duplicates as relocated gamma duplicates. In Arabidopsis thaliana, relocated gamma, WGD and single-gene duplicates have distinct features with regard to gene functions, essentiality, and protein interactions. Relative to gamma duplicates, relocated gamma duplicates have higher non-synonymous substitution rates, but comparable levels of expression and regulation divergence. Thus, relocated gamma duplicates should be distinguished from WGD and single-gene duplicates for evolutionary investigations. Our results suggest large-scale gene relocations following the gamma event were associated with the diversification of core eudicots. PMID- 27195962 TI - Analysis of workers' compensation claims data for machine-related injuries in metal fabrication businesses. AB - BACKGROUND: Metal fabrication workers are at high risk for machine-related injury. Apart from amputations, data on factors contributing to this problem are generally absent. METHODS: Narrative text analysis was performed on workers' compensation claims in order to identify machine-related injuries and determine work tasks involved. Data were further evaluated on the basis of cost per claim, nature of injury, and part of body. RESULTS: From an initial set of 4,268 claims, 1,053 were classified as machine-related. Frequently identified tasks included machine operation (31%), workpiece handling (20%), setup/adjustment (15%), and removing chips (12%). Lacerations to finger(s), hand, or thumb comprised 38% of machine-related injuries; foreign body in the eye accounted for 20%. Amputations were relatively rare but had highest costs per claim (mean $21,059; median $11,998). CONCLUSIONS: Despite limitations, workers' compensation data were useful in characterizing machine-related injuries. Improving the quality of data collected by insurers would enhance occupational injury surveillance and prevention efforts. Am. J. Ind. Med. 59:656-664, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27195963 TI - On the joys of perceiving: Affect as feedback for perceptual predictions. AB - How we perceive, attend to, or remember the stimuli in our environment depends on our preferences for them. Here we argue that this dependence is reciprocal: pleasures and displeasures are heavily dependent on cognitive processing, namely, on our ability to predict the world correctly. We propose that prediction errors, inversely weighted with prior probabilities of predictions, yield subjective experiences of positive or negative affect. In this way, we link affect to predictions within a predictive coding framework. We discuss how three key factors - uncertainty, expectations, and conflict - influence prediction accuracy and show how they shape our affective response. We demonstrate that predictable stimuli are, in general, preferred to unpredictable ones, though too much predictability may decrease this liking effect. Furthermore, the account successfully overcomes the "dark-room" problem, explaining why we do not avoid stimulation to minimize prediction error. We further discuss the implications of our approach for art perception and the utility of affect as feedback for predictions within a prediction-testing architecture of cognition. PMID- 27195964 TI - Ameloblastic carcinoma: a Brazilian collaborative study of 17 cases. AB - AIMS: Ameloblastic carcinoma (AMECA) is an odontogenic malignancy that combines the histological features of ameloblastoma and cytological atypia. Because of its rarity, it poses difficulties in diagnosis. The aim of this study was to investigate the socio-demographic data, histopathology, immunohistochemical features, treatment and outcomes of 17 cases. METHODS AND RESULTS: Descriptive statistical analyses were used to portray the clinicopathological data collected, retrospectively. Log-rank tests were performed to determine new prognostic factors. Lesions were immunostained for Ki67, p16, p53, and cytokeratins (CKs), and compared with solid/multicystic ameloblastomas (n = 15). AMECA was mostly diagnosed at a late stage, affecting the posterior mandible of male patients in their fifth decade of life. Recurrence was diagnosed in nearly 90% of treated patients, and metastasis occurred in four patients. The mean number of Ki67 positive cells was 86.4 +/- 66 per field. Tumours were focally positive for CK7, CK8, CK14, and CK18, and diffusely positive for CK19, p53, and p16. AMECA showed increased immunoexpression of CK18, CK19, p16, p53 and Ki67 as compared with benign cases. CONCLUSIONS: Our study has contributed to the improved characterization of the epidemiology, prognostic markers, treatment options and outcomes of AMECA. Current criteria must be reviewed to simplify the diagnostic process for these neoplasms. PMID- 27195965 TI - Multi-Dimensional Impact of the Public-Private Center for Translational Molecular Medicine (CTMM) in the Netherlands: Understanding New 21(st) Century Institutional Designs to Support Innovation-in-Society. AB - Knowledge translation is at the epicenter of 21st century life sciences and integrative biology. Several innovative institutional designs have been formulated to cultivate knowledge translation. One of these organizational innovations has been the Center for Translational Molecular Medicine (CTMM), a multi-million public-private partnership in the Netherlands. The CTMM aims to accelerate molecular diagnostics and imaging technologies to forecast disease susceptibilities in healthy populations and early diagnosis and personalized treatment of patients. This research evaluated CTMM's impact on scientific, translational, clinical, and economic dimensions. A pragmatic, operationally defined process indicators approach was used. Data were gathered from CTMM administrations, through a CTMM-wide survey (n = 167) and group interviews. We found that the CTMM focused on disease areas with high human, clinical, and economic burden to society (i.e., oncology, cardiovascular, neurologic, infection, and immunity diseases). CTMM displayed a robust scientific impact that rests 15%-80% above international reference values regarding publication volume and impact. Technology translation to the clinic was accelerated, with >50% of projects progressing from pre-clinical development to clinical testing within 5 years. Furthermore, CTMM has generated nearly 1500 Full Time Equivalent (FTE) of translational R&D capacity. Its positive impact on translational, (future) clinical, and economic aspects is recognized across all surveyed stakeholders. As organizational innovation is increasingly considered critical to forge linkages between life sciences discoveries and innovation-in-society, lessons learned from this study may inform other institutions with similar objectives such as the Clinical and Translational Science Awards (CTSA) Program of the National Institutes of Health (NIH) in the United States. PMID- 27195966 TI - Adenosine Hypothesis of Antipsychotic Drugs Revisited: Pharmacogenomics Variation in Nonacute Schizophrenia. AB - The existing antipsychotic therapy is based on dopamine hyperfunction and glutamate hypofunction hypotheses of schizophrenia. Adenosine receptors (ADORA) have a neuromodulatory role and can control dopaminergic and glutamatergic systems. To elucidate the effect of ADORA polymorphisms on psychopathological symptoms and adverse effects in patients with schizophrenia on long-term antipsychotic treatment, we examined 127 nonacute schizophrenia outpatients in a cross-sectional study using the Positive and Negative Symptoms Scale, Simpson Angus Scale, Barnes Akathisia Rating Scale, and Abnormal Involuntary Movement Scale. All patients were genotyped for 18 polymorphisms in ADORA1, ADORA2A, and ADORA3. We found an association between ADORA1 rs3766566 and psychopathological symptoms (p = 0.006), in particular, with positive psychopathological symptoms (p = 0.010) and general psychopathological symptoms (p = 0.023), between ADORA2A rs2298383 and general psychopathological symptoms (p = 0.046), and between ADORA2A rs5751876 and akathisia (p = 0.015). Haplotype analysis showed an association between ADORA1 CTCAACG haplotype and overall psychopathological symptoms (p = 0.019), positive psychopathological symptoms (p = 0.021), and akathisia (p = 0.028). ADORA2A TCCTC haplotype was associated with parkinsonism (p = 0.014). ADORA3 CACTAC was associated with akathisia (p = 0.042), whereas CACTAT was associated with akathisia (p = 0.045) and tardive dyskinesia (p = 0.023). The results of this first comprehensive study on ADORA polymorphisms in patients with nonacute schizophrenia receiving long-term antipsychotic therapy suggest an important neuromodulatory role of ADORA receptors in both psychopathological symptoms and adverse effects of antipsychotics. PMID- 27195967 TI - Toward Novel Diagnostics for Primary Open-Angle Glaucoma? An Association Study of Polymorphic Variation in Ras Homolog Family Member (A, B, C, D) Genes RHOA, RHOB, RHOC, and RHOD. AB - The annual economic burden of visual disorders in the United States was estimated as $139 billion. The World Health Organization has listed glaucoma in the top 10 priority eye diseases. Primary open-angle glaucoma (POAG) is a common subtype, with a lack of clinical tools for early diagnosis. The Rho GTPases belong to the Ras superfamily of proteins; the RhoA immunostaining in the optic nerve head in human glaucoma is reportedly increased. We investigated the association of polymorphisms in the Ras Homolog Family Member A, B, C, and D genes (RHOA, RHOB, RHOC, and RHOD, respectively). In a total sample of 361 unrelated subjects (179 patients with POAG and 182 age- and sex-matched healthy controls), RHOA (rs6784820, rs974495), RHOB (rs62121967), RHOC (rs11102522), and RHOD (rs61891303, rs2282502) polymorphisms were characterized by the BioMark HD dynamic array system with real-time polymerarse chain reaction. Among these candidate genetic markers and considering the Bonferroni correction, RHOA rs974495 polymorphism was significantly associated with POAG (p = 0.0011), with the TT genotype increasing the disease risk 4.9 times (95% CI 1.630-15.023). The allele and haplotype distributions of the above RHO candidate polymorphisms did not diplay a significant association. This is the first study, to the best of our knowledge, to identify a significant genotypic association between POAG and RHOA gene rs974495 polymorphism. These observations warrant replication in independent samples in the pursuit of precision medicine for rapid and early glaucoma diagnosis, and molecular targets for innovation in therapeutics of this common eye disease. PMID- 27195969 TI - Whole Exome Sequencing in a Rare Disease: A Patient with Anomalous Left Coronary Artery from the Pulmonary Artery (Bland-White-Garland Syndrome). PMID- 27195968 TI - A Network Biology Approach to Decipher Stress Response in Bacteria Using Escherichia coli As a Model. AB - The development of drug-resistant pathogenic bacteria poses challenges to global health for their treatment and control. In this context, stress response enables bacterial populations to survive extreme perturbations in the environment but remains poorly understood. Specific modules are activated for unique stressors with few recognized global regulators. The phenomenon of cross-stress protection strongly suggests the presence of central proteins that control the diverse stress responses. In this work, Escherichia coli was used to model the bacterial stress response. A Protein-Protein Interaction Network was generated by integrating differentially expressed genes in eight stress conditions of pH, temperature, and antibiotics with relevant gene ontology terms. Topological analysis identified 24 central proteins. The well-documented role of 16 central proteins in stress indicates central control of the response, while the remaining eight proteins may have a novel role in stress response. Cluster analysis of the generated network implicated RNA binding, flagellar assembly, ABC transporters, and DNA repair as important processes during response to stress. Pathway analysis showed crosstalk of Two Component Systems with metabolic processes, oxidative phosphorylation, and ABC transporters. The results were further validated by analysis of an independent cross-stress protection dataset. This study also reports on the ways in which bacterial stress response can progress to biofilm formation. In conclusion, we suggest that drug targets or pathways disrupting bacterial stress responses can potentially be exploited to combat antibiotic tolerance and multidrug resistance in the future. PMID- 27195971 TI - Alkoxy-Terminated Si Surfaces: A New Reactive Platform for the Functionalization and Derivatization of Silicon Quantum Dots. AB - Alkoxy-terminated silicon quantum dots (SiQDs) were synthesized via hydrosilylation of aliphatic ketones on hydride-terminated SiQD (H-SiQD) surfaces under microwave-irradiation. Aromatic ketones undergo hydrosilylation on H-SiQD surfaces at room temperature without requiring any catalyst. The alkoxy terminated SiQDs are soluble in organic solvents, colloidally stable, and show bright and size dependent photoluminescence (PL). The alkoxy-functionalized silicon surfaces were used as reactive platform for further functionalization via unprecedented ligand exchange of the alkoxy-surface groups with alkyl or alkenyl surface groups in the presence of BH3.THF. Proton nuclear magnetic resonance ((1)H NMR), Fourier transform infrared (FTIR), and X-ray photoelectron spectroscopy (XPS) spectroscopy confirmed alkoxy-terminated surfaces and their ligand exchange reactions in the presence of various alkenes and alkynes. PMID- 27195970 TI - NKp46-mediated Dicer1 inactivation results in defective NK-cell differentiation and effector functions in mice. AB - MicroRNAs control developmental pathways and effector functions in immune cells. Previous studies have studied the role of microRNAs in natural killer (NK) cells. However, the mouse models of microRNA depletion used were nonNK-specific and only partially depleting, hampering the interpretation of the data obtained. To clarify the role of microRNAs in murine NK cells, we deleted the RNase III enzyme Dicer1 in NKp46-expressing cells. We observed a drastic decrease in several microRNAs specifically in NK cells. Furthermore, the overall size of the "NK cell" pool was severely decreased, a phenotype associated with compromised survival. Moreover, performing a broad flow cytometry profiling, we show that Dicer1-deficient NK cells failed to complete their differentiation program. In particular, several integrins were inappropriately expressed in mature NK cells. These defects coincided with decreased response to IL-15, a cytokine responsible for "NK-cell" maturation and survival. In addition, Dicer1 deletion impaired key "NK-cell" functions: target cell killing and production of IFN-gamma, leading to defective control of metastasis. Dicer1 deletion thus affects "NK-cell" biology in a cell intrinsic manner at several distinct stages. PMID- 27195974 TI - Preanalytical, analytical, and biological variation of blood plasma submicron particle levels measured with nanoparticle tracking analysis and tunable resistive pulse sensing. AB - BACKGROUND: Nanoparticle tracking analysis (NTA) and tunable resistive pulse sensing (TRPS) enable measurement of extracellular vesicles (EVs) in blood plasma but also measure other particles present in plasma. Complete isolation of EVs from similarly sized particles with full EV recovery is currently not possible due to limitations in existing isolation techniques. AIM: This study aimed to evaluate preanalytical, analytical, and biological variation of particle measurements with NTA and TRPS on blood plasma. METHODS: Blood from 20 healthy subjects was sampled in the fasting and postprandial state. Platelet free plasma (PFP) was analyzed immediately and after a freeze-thaw cycle. Additionally, the effect of prandial state and a freeze-thaw cycle on EV-enriched particle fractions obtained via size-exclusion chromatography (SEC) was examined. RESULTS: We observed analytical linearity in the range of 1.0-10.0 * 10(8) particles/mL for NTA and 1.0 * 10(8)-1.8 * 10(9) particles/mL for TRPS. The analytical variation was generally below 10%. A considerable intra- and inter-individual variation was demonstrated with estimated reference intervals of 1.4 * 10(11)-1.2 * 10(12) particles/mL for NTA and 1.8 * 10(8)-1.6 * 10(9) particles/mL for TRPS. Food intake and to a lesser extent a freeze-thaw cycle affected particle populations in PFP and, similarly, in EV-enriched fractions. CONCLUSION: In this study NTA and TRPS enabled acceptably precise concentration and size measurement of submicron particles in PFP. An appreciable intra- and inter-individual biological variation was observed. In studies on particle populations in PFP or EV-enriched fractions, we recommend analysis of fresh, fasting samples. PMID- 27195975 TI - Cystometric evaluation of recovery in hypocompliant defunctionalized bladder as a result of long-term dialysis after kidney transplantation. AB - OBJECTIVES: To evaluate the functional recovery of a pretransplant hypocompliant bladder in patients without neurological disorders, and to determine its relationship with ureteral complications, including vesicoureteral reflux. METHODS: A total of 61 patients without neurogenic disorders, who underwent video water cystometry pre- and 1 year post-transplantation, were enrolled. Cystometric bladder capacity and maximum intravesical pressure were measured, and compliance was calculated by the elevation in intravesical pressure as a result of an increase in volume. The frequencies of urinary complications, including urinary leakage, pyelonephritis and vesicoureteral reflux, were also evaluated. RESULTS: Pretransplant dialysis duration correlated with pretransplant bladder capacity and compliance (R(2) = 0.421, P < 0.001 and R(2) = 0.418, P < 0.001, respectively). A total of 16 (26.2%) patients had hypocompliant bladders <10 mL/cmH2 O, whereas 10 of the 12 patients (83.3%) with pretransplant dialysis duration of more than 5 years had a pretransplant hypocompliant bladder. Bladder compliance significantly recovered to >20 mL/cmH2 O (21.1-286.0) at 1 year post transplantation in all 16 patients with a pretransplant hypocompliant bladder. No significant differences were observed for urinary leakage, pyelonephritis or vesicoureteral reflux between patients with and without a pretransplant hypocompliant bladder. CONCLUSIONS: Bladder compliance decreases logarithmically pretransplantation according to dialysis duration. Although the ability of the patients to recover varies, dysfunctions associated with a pretransplant hypocompliant bladder recover to normal ranges after renal transplantation. A pretransplant hypocompliant bladder seems not to be associated with the post transplant prevalence of urinary complications or vesicoureteral reflux. PMID- 27195976 TI - Controllability of protein-protein interaction phosphorylation-based networks: Participation of the hub 14-3-3 protein family. AB - Posttranslational regulation of protein function is an ubiquitous mechanism in eukaryotic cells. Here, we analyzed biological properties of nodes and edges of a human protein-protein interaction phosphorylation-based network, especially of those nodes critical for the network controllability. We found that the minimal number of critical nodes needed to control the whole network is 29%, which is considerably lower compared to other real networks. These critical nodes are more regulated by posttranslational modifications and contain more binding domains to these modifications than other kinds of nodes in the network, suggesting an intra group fast regulation. Also, when we analyzed the edges characteristics that connect critical and non-critical nodes, we found that the former are enriched in domain-to-eukaryotic linear motif interactions, whereas the later are enriched in domain-domain interactions. Our findings suggest a possible structure for protein protein interaction networks with a densely interconnected and self-regulated central core, composed of critical nodes with a high participation in the controllability of the full network, and less regulated peripheral nodes. Our study offers a deeper understanding of complex network control and bridges the controllability theorems for complex networks and biological protein-protein interaction phosphorylation-based networked systems. PMID- 27195977 TI - Histologic Assessment of Intratumoral Lymphoplasmacytic Infiltration Is Useful in Predicting Prognosis of Patients with Hepatocellular Carcinoma. AB - In the present study, we investigated the clinicopathologic significance of intratumoral lymphoplasmacytic infiltration in a large cohort of patients with solitary hepatocellular carcinoma (HCC). Based on examination of hematoxylin and eosin-stained sections, significant infiltration was defined as dense lymphoplasmacytic infiltration, either multifocal or diffuse, in 2 or more fields under low-power magnification. Of 544 cases, 216 (39.7%) were positive for significant infiltration (HCC-LI group), while 328 (60.3%) were negative (HCC-NLI group). There were no significant between-group differences in patient age, sex, or background etiology. The lower incidence of Child-Pugh stage B (P = 0.001) and lower level of indocyanine green retention rate at 15 minutes (P < 0.001) in the HCC-LI group indicated better liver function in this group. Histologically, tumors were significantly smaller in size in the HCC-LI group than in the HCC-NLI group (P < 0.001). In addition, prominent neutrophilic infiltration, interstitial fibrosis and tumor steatosis were significantly more frequent (P < 0.001) in the HCC-LI group, while tumor necrosis was significantly less frequent (P = 0.008). Kaplan-Meier analyses revealed that overall and recurrence-free survival were significantly better in the HCC-LI group (P < 0.001). Multivariate Cox regression analysis showed that intratumoral lymphoplasmacytic infiltration was independently prognostic of both overall and recurrence-free survival (P < 0.001), with absence of infiltration showing high Cox-hazard ratios for poor prognosis. In conclusion, intratumoral lymphoplasmacytic infiltration, as determined by assessment of hematoxylin and eosin-stained slides, was significantly associated with the clinical and pathologic features of HCC and has profound prognostic importance. PMID- 27195978 TI - Induction, labor length and mode of delivery: the impact on preeclampsia-related adverse maternal outcomes. AB - OBJECTIVE: The objectives were to evaluate whether induction, specifically prolonged labor, was associated with adverse maternal outcomes related to preeclampsia with severe features (PEC-S) and whether cesarean affected the rate. STUDY DESIGN: This was a retrospective cohort study of women with PEC-S ?34 weeks who were diagnosed either before planned cesarean or before induction/latent labor. The primary outcome was a composite adverse maternal outcome related to PEC-S. RESULTS: The final cohort comprised 193 women (n=172 with labor and n=21 with planned cesarean). The prevalence of the outcome was 15.5%. Women exposed to labor did not have a higher rate compared with planned cesarean (16.3% vs 9.5%, P=0.4). Adjusting for confounders, women with a cesarean after prolonged labor had a 10-fold higher adverse outcome risk compared with women with a planned cesarean (adjusted odds ratio (aOR) 9.7 (1.2 to 78.6), P=0.03) or with a vaginal delivery <24 h (aOR 9.7 (1.4 to 67.4), P=0.02). CONCLUSION: Prolonged labor and cesarean in labor were both associated with an increase in our outcome. PMID- 27195979 TI - Does hyperglycemia in hypernatremic preterm infants increase the risk of intraventricular hemorrhage? AB - OBJECTIVE: Hypernatremia and hyperglycemia are highly prevalent in preterm infants during the first week after birth, and both can lead to hyperosmolarity and osmotic shifts. The objective is to determine whether hyperglycemia increases the risk of intraventricular hemorrhage (IVH) in hypernatremic preterm infants. STUDY DESIGN: Single-center retrospective medical record review of 216 infants <1000 g birth weight and <29 weeks gestational age (admitted over a 9-year period) who had serum sodium levels and blood glucose levels monitored at least every 24 h and more frequently if indicated during the first 10 days after birth. Hyperglycemia was defined as persistently high blood glucose (usually >200 mg dl( 1)) treated with an insulin infusion. Hypernatremia was defined as a serum sodium level of ?150 mmol l(-1) on repeated measurements. RESULTS: Of the 216 infants studied, 76 (35%) developed hyperglycemia and 126 (58%) developed hypernatremia. IVH developed more frequently in infants with hyperglycemia (P=0.006, odds ratio (OR) 2.3, 95% confidence interval (CI) 1.3 to 4.1), in infants with hypernatremia (P=0.018, OR 2.0, 95% CI 1.2 to 3.5) and in infants with hypernatremia plus hyperglycemia (P=0.001, OR 3.2, 95% CI 1.6 to 6.4). Multivariate regression analysis confirmed the independent association of higher risk of IVH with the presence of hypernatremia plus hyperglycemia (P=0.015, OR 2.6, 95% CI 1.2 to 5.5) but not with hypernatremia or hyperglycemia alone. CONCLUSION: Hyperglycemia increases the risk of IVH in hypernatremic preterm infants. PMID- 27195980 TI - Examining pregnancy-specific smartphone applications: what are patients being told? AB - OBJECTIVE: The objective of this study is to evaluate the informative content of two free, pregnancy-specific smartphone applications and their accuracy and adherence to prenatal care guidelines. STUDY DESIGN: This is a qualitative analysis of the information delivered through two free, pregnancy-specific smartphone applications (apps): Text4Baby (T4B) and Baby Center's 'My Pregnancy Today' (BC). All information from conception through 2 weeks postpartum were transcribed and coded independently by two physician researchers. Content was analyzed and assigned thematic codes. The proportion of content each app delivered per theme was then calculated and the chi(2)-test was used to compare thematic frequency between apps. RESULTS: A total of 609 pieces of daily content were transcribed; 698 message themes were coded and analyzed. Most information delivered by T4B was about fetal development (23.8%) or prenatal care (16.6%); most content from BC was about normal pregnancy symptoms (20.1%) or maternal well being (21.1%); the differences between apps for each of these themes were statistically significant (P<0.05). A total of four messages contained incomplete or ambiguous content; neither app delivered overtly incorrect medical information. T4B and BC had a similar proportion of information that was in-line with the American College of Obstetrics and Gynecology Guidelines for Prenatal Care. Neither app delivered any messages about contraception. CONCLUSION: T4B and BC are free, pregnancy-specific apps with different focuses. Neither app delivers comprehensive prenatal information, as evidenced by the absence of information about postpartum contraception. More information is needed to determine the role of such apps in prenatal care. PMID- 27195982 TI - Metal-Organic Framework Based on Isonicotinate N-Oxide for Fast and Highly Efficient Aqueous Phase Cr(VI) Adsorption. AB - Synthesis of new porous materials has been developed for efficient capture of pollutants in environmental sciences. Here, the application of a new metal organic framework (TMU-30) has been reported based on isonicotinate N-oxide as an adsorptive site for fast and highly efficient aqueous phase adsorption of Cr(VI). The adsorption process showed no remarkable effect over a pH range of 2-9. The maximum capacity of the adsorption was reached in just less than 10 min and followed the pseudo-second-order kinetics. The maximum capacity of 2.86 mol mol( 1) (145 mg/g) was obtained according to Langmuir model at 298 K. The spontaneous adsorption and an endothermic process were controlled by positive entropy changes. XPS analysis revealed electrostatic interactions between N-oxide groups of TMU-30 and Cr(VI) species, which were responsible for the adsorption process. PMID- 27195981 TI - The use of short message services (SMS) to provide medical updating to parents in the NICU. AB - OBJECTIVE: Premature delivery and prolonged hospitalization of infants in the neonatal intensive care unit (NICU) are very stressful for parents. As technology has advanced, short message services (SMS) have been used increasingly in the medical disciplines. To date, the use of SMS for updating patients and families regarding medical information has not been reported. We implemented the SMS technique to daily update the parents regarding the health status of their preterm infant. The objective of this study was to evaluate the use of SMS technology and to assess its impact on the parents and the nursing staff. STUDY DESIGN: Parents and nurses completed questionnaires at two time periods: pre-SMS implementation (pre-SMSi) and post-SMS implementation (post-SMSi). The parent questionnaires included statements about medical information delivery, communication and trust between parents and medical staff, parental anxiety and overall satisfaction. The nurse questionnaires included statements about the expected and actual impact on their workload. RESULTS: Comparison of the parents' responses at the two time periods indicated that in the post-SMSi time period, they felt that the physician was more available when needed (P=0.002), they were more comfortable about approaching the physician (P=0.001) and more satisfied with the medical information provided by the staff (P=0.03). In the post-SMSi period, 78.1% of the nurses noted that the SMS communication is a convenient and user-friendly method. CONCLUSIONS: SMS updating is an easy and user-friendly technology that enriches the modalities of information delivery to parents of hospitalized preterm infants. It is a complementary and useful tool for encouraging and improving personal communication between parents and medical staff and should be considered part of quality improvement in health care. PMID- 27195983 TI - Improved Predictions of the Geographic Distribution of Invasive Plants Using Climatic Niche Models. AB - Climatic niche models for invasive plants are usually constructed with occurrence records taken from literature and collections. Because these data neither discriminate among life-cycle stages of plants (adult or juvenile) nor the origin of individuals (naturally established or man-planted), the resulting models may mispredict the distribution ranges of these species. We propose that more accurate predictions could be obtained by modelling climatic niches with data of naturally established individuals, particularly with occurrence records of juvenile plants because this would restrict the predictions of models to those sites where climatic conditions allow the recruitment of the species. To test this proposal, we focused on the Peruvian peppertree (Schinus molle), a South American species that has largely invaded Mexico. Three climatic niche models were constructed for this species using high-resolution dataset gathered in the field. The first model included all occurrence records, irrespective of the life cycle stage or origin of peppertrees (generalized niche model). The second model only included occurrence records of naturally established mature individuals (adult niche model), while the third model was constructed with occurrence records of naturally established juvenile plants (regeneration niche model). When models were compared, the generalized climatic niche model predicted the presence of peppertrees in sites located farther beyond the climatic thresholds that naturally established individuals can tolerate, suggesting that human activities influence the distribution of this invasive species. The adult and regeneration climatic niche models concurred in their predictions about the distribution of peppertrees, suggesting that naturally established adult trees only occur in sites where climatic conditions allow the recruitment of juvenile stages. These results support the proposal that climatic niches of invasive plants should be modelled with data of naturally established individuals because this improves the accuracy of predictions about their distribution ranges. PMID- 27195984 TI - Evaluating Infection Prevention Strategies in Out-Patient Dialysis Units Using Agent-Based Modeling. AB - Patients receiving chronic hemodialysis (CHD) are among the most vulnerable to infections caused by multidrug-resistant organisms (MDRO), which are associated with high rates of morbidity and mortality. Current guidelines to reduce transmission of MDRO in the out-patient dialysis unit are targeted at patients considered to be high-risk for transmitting these organisms: those with infected skin wounds not contained by a dressing, or those with fecal incontinence or uncontrolled diarrhea. Here, we hypothesize that targeting patients receiving antimicrobial treatment would more effectively reduce transmission and acquisition of MDRO. We also hypothesize that environmental contamination plays a role in the dissemination of MDRO in the dialysis unit. To address our hypotheses, we built an agent-based model to simulate different treatment strategies in a dialysis unit. Our results suggest that reducing antimicrobial treatment, either by reducing the number of patients receiving treatment or by reducing the duration of the treatment, markedly reduces overall colonization rates and also the levels of environmental contamination in the dialysis unit. Our results also suggest that improving the environmental decontamination efficacy between patient dialysis treatments is an effective method for reducing colonization and contamination rates. These findings have important implications for the development and implementation of future infection prevention strategies. PMID- 27195987 TI - Cognitive deficits after aneurysmal and angiographically negative subarachnoid hemorrhage: Memory, attention, executive functioning, and emotion recognition. AB - OBJECTIVE: The authors' aim was to investigate cognitive outcome in patients with aneurysmal and angiographically negative subarachnoid hemorrhage (aSAH and anSAH), by comparing them to healthy controls and to each other. Besides investigating cognitive functions as memory and attention, they focused on higher order prefrontal functions, namely executive functioning (EF) and emotion recognition. METHOD: Patients and healthy controls were assessed with tests measuring memory (15 Words Test, Digit Span), attention and processing speed (Trail Making Test A and B), EF (Zoo Map, Letter Fluency, Dysexecutive Questionnaire), and emotion recognition (Facial Expressions of Emotion Stimuli and Tests). Between-groups comparisons of test performances were made. RESULTS: Patients with aSAH scored significantly lower than healthy controls on measures of memory, processing speed, and attention, but anSAH patients did not. In the higher-order prefrontal functions (EF and emotion recognition), aSAH patients were clearly impaired when compared to healthy controls. However, anSAH patients did not perform significantly better than aSAH patients on the majority of the tests. CONCLUSIONS: In the subacute phase after SAH, cognitive functions, including the higher-order prefrontal functions EF and emotion recognition, were clearly impaired in aSAH patients. Patients with anSAH did not perform better than aSAH patients, which indicates that these functions may also be affected to some extent in anSAH patients. Considering the importance of these higher-order prefrontal functions for daily life functioning, and following the results of the present study, tests that measure emotion recognition and EF should be part of the standard neuropsychological assessment after SAH. (PsycINFO Database Record PMID- 27195988 TI - The neural mechanism of hedonic processing and judgment of pleasant odors: An activation likelihood estimation meta-analysis. AB - OBJECTIVE: Pleasure is essential to normal healthy life. Olfaction, as 1 of the neurobehavioral probes of hedonic capacity, has a unique advantage compared to other sensory modalities. However, it is unclear how olfactory hedonic information is processed in the brain. This study aimed to investigate olfactory hedonic processing in the human brain. METHOD: We conducted an activation likelihood estimation (ALE) meta-analysis on 16 functional imaging studies that examined brain activation in olfactory hedonic processing-related tasks in healthy adults. RESULTS: The results show that there is a core olfactory hedonic processing network, which consists of the bilateral parahippocampal gyrus/amygdala (BA34), the left middle frontal gyrus (BA6), the right middle frontal gyrus/lateral orbitofrontal cortex (OFC; BA10), the bilateral cingulate gyrus (BA32), the right lentiform nucleus/lateral globus pallidus, the right medial frontal gyrus/medial OFC (BA11), the left superior frontal gyrus (BA10), and the right insula (BA13). Moreover, our findings highlight that the right hemisphere is predominant in explicit odor hedonic judgment. Finally, the results indicate that there are significant differences in brain activation for hedonic judgment and passive smelling. CONCLUSION: These results support the hypothesis that the OFC plays a key role in explicit hedonic judgment. (PsycINFO Database Record PMID- 27195985 TI - HIV-1 Genetic Variation Resulting in the Development of New Quasispecies Continues to Be Encountered in the Peripheral Blood of Well-Suppressed Patients. AB - As a result of antiretroviral therapeutic strategies, human immunodeficiency virus type 1 (HIV-1) infection has become a long-term clinically manageable chronic disease for many infected individuals. However, despite this progress in therapeutic control, including undetectable viral loads and CD4+ T-cell counts in the normal range, viral mutations continue to accumulate in the peripheral blood compartment over time, indicating either low level reactivation and/or replication. Using patients from the Drexel Medicine CNS AIDS Research and Eradication Study (CARES) Cohort, whom have been sampled longitudinally for more than 7 years, genetic change was modeled against to the dominant integrated proviral quasispecies with respect to selection pressures such as therapeutic interventions, AIDS defining illnesses, and other factors. Phylogenetic methods based on the sequences of the LTR and tat exon 1 of the HIV-1 proviral DNA quasispecies were used to obtain an estimate of an average mutation rate of 5.3 nucleotides (nt)/kilobasepair (kb)/year (yr) prior to initiation of antiretroviral therapy (ART). Following ART the baseline mutation rate was reduced to an average of 1.02 nt/kb/yr. The post-ART baseline rate of genetic change, however, appears to be unique for each patient. These studies represent our initial steps in quantifying rates of genetic change among HIV-1 quasispecies using longitudinally sampled sequences from patients at different stages of disease both before and after initiation of combination ART. Notably, while long term ART reduced the estimated mutation rates in the vast majority of patients studied, there was still measurable HIV-1 mutation even in patients with no detectable virus by standard quantitative assays. Determining the factors that affect HIV-1 mutation rates in the peripheral blood may lead to elucidation of the mechanisms associated with changes in HIV-1 disease severity. PMID- 27195989 TI - Biosimilars in rheumatology: out of the laboratory and into practice. PMID- 27195990 TI - Tailoring of the porous structure of soft emulsion-templated polymer materials. AB - This paper discusses the formation of soft porous materials obtained by the polymerization of inverse water-in-silicone (polydimethylsiloxane, PDMS) emulsions. We show that the initial state of the emulsion has a strong impact on the porous structure and properties of the final material. We show that using a surfactant with different solubilities in the emulsion continuous phase (PDMS), it is possible to tune the interaction between emulsion droplets, which leads to materials with either interconnected or isolated pores. These two systems present completely different behavior upon drying, which results in macroporous air filled materials in the interconnected case and in a collapsed material with low porosity in the second case. Finally, we compare the mechanical and acoustical properties of these two types of bulk polymer monoliths. We also describe the formation of micrometric polymer particles (beads) in these two cases. We show that materials with an interconnected macroporous structure have low mechanical moduli and low sound speed, and are suitable for acoustic applications. The mechanical and acoustical properties of the materials with a collapsed porous structure are similar to those of non-porous silicone, which makes them acoustically inactive. PMID- 27195992 TI - Copy Number Variants and Congenital Anomalies Surveillance: A Suggested Coding Strategy Using the Royal College of Paediatrics and Child Health Version of ICD 10. AB - The use of array-based comparative genomic hybridization to assess DNA copy number is increasing in many jurisdictions. Such technology identifies more genetic causes of congenital anomalies; however, the clinical significance of some results may be challenging to interpret. A coding strategy to address cases with copy number variants has recently been implemented by the Alberta Congenital Anomalies Surveillance System and is described. PMID- 27195991 TI - Associations between Sleep Duration and Indicators of Cardiometabolic Disease in Canadian Children and Adolescents: Analyses of the 2007-2009 Canadian Health Measures Survey. AB - BACKGROUND: Indicators of cardiometabolic disease-including obesity, hyperinsulinemia, and dyslipidemia-are associated with an increased risk of cardiovascular disease and type 2 diabetes. Rates of obesity and type 2 diabetes in Canadian children and adolescents have increased rapidly in recent years; research exploring modifiable risk factors is critical. Experimental and epidemiological research demonstrates that partial sleep loss is linked with deteriorations in indicators of cardiometabolic health. The objectives of this study are (1) to examine associations between short sleep duration and indicators of cardiometabolic disease in Canadian children and adolescents and (2) to identify determinants of short sleep duration in this population. METHODS: Logistic regression models were developed to examine associations between sleep duration and indicators of cardiometabolic disease and to identify predictors of short sleep duration. RESULTS: Compared with longer sleepers, children and adolescents with short sleep duration had greater odds of being overweight or obese. Sex- and age-stratified analyses indicated that short sleep duration was linked with greater odds of overweight/obesity in boys and adolescents only. Short sleepers did not have greater odds of having hyperinsulinemia, low HDL cholesterol, or high triglycerides. Age was a strong predictor of inadequate sleep duration. CONCLUSION: Future studies should include longitudinal designs that address whether short sleep duration in boys and in adolescents contributes directly to the development of overweight and obesity. PMID- 27195993 TI - Validating Procedures used to Identify Duplicate Reports in Haiti's National HIV/AIDS Case Surveillance System. AB - OBJECTIVES: Valid deduplication of human immunodeficiency virus (HIV) case reports is critical to the utility of these data to inform HIV programs. The Haitian Ministry of Health (MSPP) and partners operate a case-based, national HIV/AIDS surveillance system (HASS), using deterministic and probabilistic procedures to identify duplicate records. These procedures are described and validated based on expert classifications. METHODS: Two samples of HASS records identified as duplicates were selected: 100 pairs from deterministic and 100 pairs from probabilistic matching procedures (total: 200 pairs, 400 case reports). Clinical data from the national electronic medical record (iSante) were reviewed and consensus gold-standard determinations on the status of duplications were made. False positive rates (FPR) were estimated by reviewing these records, while false negative rates were calculated (FNR) by using LinkPlusTM probabilistic linkage software. The effect of deduplication on total HIV case counts was demonstrated. RESULTS: Review of deterministic matches yielded 99 true positives and 1 false positive (FPR, 1 per 100; 95% CI, 0.71-5.4). Review of probabilistic matches yielded a FPR of 6 per 100 (95% CI, 2.7-12.4). LinkPlus identified 1,491 probable matches among 68,393 records, representing a FNR of 2 per 100 (95% CI, 0.55-7.0). After adjustment, the estimated unique count of reported HIV patients in HASS was 211,885 (95% CI, 207, 293-213, 232) as of December 2013. CONCLUSIONS: Based on application of the established procedures, HASS conforms to the duplication performance standard recommended by the Centers for Disease Control and Prevention for HIV surveillance. PMID- 27195995 TI - Collaborative Development and Results of a Nigerian Trauma Registry. AB - BACKGROUND: More than 90% of injury-related deaths and disabilities occur in low- and middle-income countries. The development of the Nigerian Trauma Registry (NTR) and the first descriptive data analysis of the patient characteristics, mechanisms of injury, injury severity, and treatments are reported. METHODS: Existing data collection tools were modified to capture a minimum data set of variables reflective of the trauma experience in Nigeria. Data are collected using the secure, Web-based application, REDCap (Research Electronic Data Capture). RESULTS: Two hospitals entered 564 patients into the registry. Motor vehicle accidents were the most frequently reported trauma (69.2%). Of the 51 fall injuries, 82% were from buildings. There were 229 mass casualties, including bus accidents (41.5%), bombings or blasts (28.8%), multiple vehicle accidents (23.6%), fires (3.1%), and civil conflicts or riots (3.1%). External soft tissue was the most commonly reported injury region followed by extremities, head and neck, face, abdomen, and thorax/spine. Only 18.1% of patients arrived by ambulance. There were 19 recorded in-hospital deaths and 79.0% of these were due to motor vehicle accidents. CONCLUSIONS: This is the largest report of injury surveillance in this country. These data are essential to inform policy makers about the increasing trauma burden and provide a strong advocacy tool, prevention opportunities, provisions for unmet capacity needs, and better allocation of limited health care resources. The NTR has demonstrated that development and implementation of an electronic trauma registry is feasible in low- and middle income countries. The NTR evolved through international collaborations that included a partnership with an American epidemiologist and 2 Nigerian hospitals that contributed their individual and institutional capabilities. Local champions are required to drive the initiation and implementation of registries. PMID- 27195996 TI - Using Data on Tumor Grade in Cancer Registries to Enhance Surveillance of Oropharyngeal Cancers in Relation to the Human Papillomavirus Epidemic. AB - BACKGROUND: Incidence rates have been increasing in US whites for squamous cell carcinoma (SCC) at anatomic sites involving the oropharynx (OP) and classified as potentially associated with human papillomavirus (HPV). Registries have not routinely collected data on HPV status of tumors. High tumor grade (poorly differentiated or undifferentiated), however, has been associated with HPV positivity in clinical studies. This study explored the potential value of adding data on tumor grade to registry-based surveillance efforts. METHODS: Data were obtained on tumor grade for 39,907 OP SCCs diagnosed in 2000-2012 at HPV associated OP sites in a research database for Surveillance, Epidemiology, and End Results (SEER) Program registries. Grade was compared by anatomic site. Annual percent change in the age-standardized incidence rate was estimated by joinpoint regression. RESULTS: HPV-associated OP SCC sites were predominantly (87%) base of tongue and tonsils (BTT). High-grade comprised 40% for BTT vs 20% 30% for other HPV-associated sites. Temporal increases in total rates for BTT were evident for whites, who had statistically significant increases for high grade but persistently low rates for low grade. Rates increased for unknown grade, reflecting a decline in cancer-directed surgery. CONCLUSIONS: Findings support the use of tumor grade for surveillance of OP SCC in relation to the HPV epidemic. Future studies should include non-SEER registries, and also examine HPV status for unknown grade and consistency in grading among pathologists. PMID- 27195994 TI - Linking the National Health Interview Survey with the Florida Cancer Data System: A Pilot Study. AB - Cancer registry data are vital for the surveillance of cancer trends, but registries are limited in the number of data items that can be collected for hypothesis-driven research. Linkage with other databases can add valuable information and is a potentially effective tool for increasing our understanding of and identifying the causes of cancer and health disparities along the cancer continuum. We conducted a pilot study to link data from the 1981-2010 Florida Cancer Data System (FCDS) with data from the 1986-2009 National Health Interview Survey (NHIS). The NHIS data contain important information on sociodemographics, screening behaviors, comorbidities, risk factors, health care access, and quality of life, which are not available from FCDS. The linkage resulted in a total of 6,281 linked cases. After removing cases with a first cancer diagnosis before 1981 (prior to FCDS creation) or missing date of diagnosis information, there were 1,908 cases diagnosed with cancer prior to their NHIS interview and 4,367 cases diagnosed after their NHIS interview. The enriched data set resulting from the linkage allows us to evaluate risk factors associated with developing cancer as well as conduct analyses on cancer survivorship issues and mortality. This pilot study demonstrates the feasibility and utility of a linkage between cancer registries and national health surveys, while also acknowledging the cost and challenges associated with such linkages. PMID- 27195997 TI - Encouraging Health Information Management Graduates to Pursue Cancer Registry Careers. AB - The cancer registry profession has grown dramatically since its inception in 1926. Certified tumor registrars (CTRs) have become an integral part of the cancer care team by providing quality cancer data for research, statistical purposes, public health, and cancer control. In addition, CTRs have been found to be valuable in other cancer and health-related fields. Based on the need for high quality, accurate data, the National Cancer Registrars Association (NCRA), the certification body for CTRs, has increased the educational requirement for eligibility for the CTR certification exam. This has resulted in fewer individuals who are able to meet the requirements for CTR certification. In addition, the existing cancer registry workforce is, on average, older than other allied health professions, and therefore will face an increasing number of retirements in the next few years. The high demand for CTRs, the decreased pool of CTR-eligible applicants, and the aging cancer registry workforce has resulted in an existing shortage that will only get worse as the population ages and the incidence of cancer increases. Health information management (HIM) students are well suited to pursuing further training in the cancer registry field and gaining the CTR credential. HIM students or new graduates have the needed skill set and education to pursue a cancer registry career. There are many avenues HIM educational programs can take to encourage students to pursue CTR certification and a cancer registry career. Including cancer registry functions in courses throughout the HIM curriculum, bringing in cancer registry speakers, encouraging networking, and promoting the cancer registry field and profession in general are just a few of the methods that HIM programs can use to raise awareness of and promote a cancer registry career to their students. Illinois State University has used these methods and has found them to be successful in encouraging a percentage of their graduates to pursue cancer registry careers. PMID- 27195998 TI - How to Build an Abstract. AB - Creating an abstract from the electronic medical record (EMR) can seem overwhelming at first. There is so much information, it is difficult to know where to start and how to work your way through all the documents in a short period of time. This article provides one roadmap to build an abstract that can provide a template for a new abstractor or an alternative way of doing things for an experienced abstractor. PMID- 27195999 TI - The Effect of Dangguijagyag-san on Mild Cognitive Impairment. AB - OBJECTIVES: The aim of this study was to evaluate the safety and the effect of dangguijagyag-san (DJS) on mild cognitive impairment (MCI). METHODS: This study examined the administration of DJS ([Formula: see text]; angelica and peony formula) and was conducted at Uijeongbu Health Center in Gyeonggi-do, Korea, in 2013. Ninety-five of 118 patients diagnosed with MCI were followed up for 1 year after the study ended, and their medical records were analyzed. RESULTS: The patients included 36 men (37.9%) and 59 women (62.1%). When the results from before the study began were compared with the results 1 year after the study ended, the overall average score according to the Korean-Montreal Cognitive Assessment (K-MOCA) showed a statistically significant increase, from 15.46 +/- 5.30 to 18.54 +/- 5.11, respectively. Both male and female patients recorded a significant increase in K-MOCA scores for all sections, including the visuospatial/executive section, the naming section, the attention section, the language section, the abstraction section, the delayed recall section, and the orientation section. Scores assessed by the Mini-Mental State Examination for Dementia Screening (MMSE-DS) showed a statistically significant increase, from 21.84 +/- 3.59 before the study to 24.43 +/- 3.13 after the study, but decreased slightly to 23.04 +/- 3.36 at the 1-year follow-up. However, MMSE-DS scores measured before the study began increased significantly when compared with scores measured 1 year after the study ended. CONCLUSIONS: DGJYS improved the cognitive skills of patients diagnosed with MCI, and no adverse effects were observed. In the future, the efficacy of DGJYS must be objectively verified by using a randomized controlled trial. PMID- 27196000 TI - Gender, Headaches, and Sleep Health in High School Students. AB - BACKGROUND: The effects of gender, headaches, and their interaction on sleep health (sleep duration, sleep onset and continuity, and indications of hypersomnolence) have not been well studied. MATERIALS AND METHODS: For American adolescents, we contrasted sleep health variables between males (n = 378) and females (n = 372) and between individuals with chronic headaches (n = 102 females and 60 males) and without chronic headaches (n = 270 females and 318 males) using data from surveys. RESULTS: Not all measures of sleep health differed between groups, but the following patterns were observed for the measures that did differ. Females reported shorter sleep durations on school nights (p = 0.001), increased likelihood of sleepiness on school days (p < 0.05), and higher hypersomnolence scores compared with males (p = 0.005). Individuals with headaches reported shorter sleep durations on weekends (p = 0.009) and higher hypersomnolence scores (p = 0.009) than individuals without headaches. Interestingly, females with headaches reported worse sleep health than females without headaches for multiple measures. Males with headaches did not differ from males without headaches, except for greater waking at night (p = 0.04). CONCLUSIONS: These results are consistent with other studies of gender-based differences in sleep health and emphasize the importance of recognizing the risk of headache in female adolescents and treating that condition to prevent additional sleep health issues. PMID- 27196002 TI - Exosome-mediated small RNA delivery for gene therapy. AB - Small RNAs, including small interfering RNAs (siRNA) and microRNAs (miRNA), are emerging as promising therapeutic drugs against a wide array of diseases. The key obstacle for the successful clinical application of small RNAs is to develop a safe delivery system directed at the target tissues only. Current small RNA transfer techniques use viruses or synthetic agents as delivery vehicles. The replacement of these delivery vehicles with a low toxicity and high target specific approach is essential for making small RNA therapy feasible. Because exosomes have the intrinsic ability to traverse biological barriers and to naturally transport functional small RNAs between cells, they represent a novel and exciting delivery vehicle for the field of small RNA therapy. As therapeutic delivery agents, exosomes will potentially be better tolerated by the immune system because they are natural nanocarriers derived from endogenous cells. Furthermore, exosomes derived from genetically engineered cells can deliver small RNAs to target tissues and cells. Thus, exosome-based delivery of small RNAs may provide an untapped, effective delivery strategy to overcome impediments such as inefficiency, nonspecificity, and immunogenic reactions. In this review, we briefly describe how exosomal small RNAs function in recipient cells. Furthermore, we provide an update and overview of new findings that reveal the potential applications of exosome-based small RNA delivery as therapeutics in clinical settings. WIREs RNA 2016, 7:758-771. doi: 10.1002/wrna.1363 For further resources related to this article, please visit the WIREs website. PMID- 27196001 TI - MEK Inhibition Sensitizes Precursor B-Cell Acute Lymphoblastic Leukemia (B-ALL) Cells to Dexamethasone through Modulation of mTOR Activity and Stimulation of Autophagy. AB - Resistance to glucocorticosteroids (GCs) is a major adverse prognostic factor in B-ALL, but the molecular mechanisms leading to GC resistance are not completely understood. Herein, we sought to elucidate the molecular background of GC resistance in B-ALL and characterize the therapeutic potential of targeted intervention in these mechanisms. Using exploratory bioinformatic approaches, we found that resistant cells exhibited significantly higher expression of MEK/ERK (MAPK) pathway components. We found that GC-resistant ALL cell lines had markedly higher baseline activity of MEK and small-molecule MEK1/2 inhibitor selumetinib increased GCs-induced cell death. MEK inhibitor similarly increased in vitro dexamethasone activity in primary ALL blasts from 19 of 22 tested patients. To further confirm these observations, we overexpressed a constitutively active MEK mutant in GC-sensitive cells and found that forced MEK activity induced resistance to dexamethasone. Since recent studies highlight the role GC-induced autophagy upstream of apoptotic cell death, we assessed LC3 processing, MDC staining and GFP-LC3 relocalization in cells incubated with either DEX, SEL or combination of drugs. Unlike either drug alone, only their combination markedly increased these markers of autophagy. These changes were associated with decreased mTOR activity and blocked 4E-BP1 phosphorylation. In cells with silenced beclin-1 (BCN1), required for autophagosome formation, the synergy of DEX and SEL was markedly reduced. Taken together, we show that MEK inhibitor selumetinib enhances dexamethasone toxicity in GC-resistant B-ALL cells. The underlying mechanism of this interaction involves inhibition of mTOR signaling pathway and modulation of autophagy markers, likely reflecting induction of this process and required for cell death. Thus, our data demonstrate that modulation of MEK/ERK pathway is an attractive therapeutic strategy overcoming GC resistance in B-ALL patients. PMID- 27196004 TI - Treatment of Early-Onset Spinal Deformity (EOSD) With VEPTR: A Challenge for the Final Correction Spondylodesis-A Case Series. AB - STUDY DESIGN: Case Series. OBJECTIVE: To describe the post-VEPTR (vertical expandable prosthetic titanium rib) treatment changes in early-onset spinal deformity (EOSD), which may influence the final correction spondylodesis. SUMMARY OF BACKGROUND DATA: The VEPTR device, originally developed for the treatment of congenital rib cage malformation, is nowadays more widely used in the treatment of EOSD. At present, only a few reports describe the possible complications that may occur with repeated lengthening procedures of the VEPTR, thereby making the final spondylodesis more complicated and less satisfactory. METHODS: X-rays of 5 children treated for EOSD with 2 unilateral VEPTR (each rib to rib and rib to lumbar lamina) were analyzed for curve patterns and Cobb angles before, during, and at the end of VEPTR treatment, and after the final spondylodesis. Intraoperative observations during the spondylodesis, which influenced the possibilities of the curve correction, were documented. RESULTS: All patients showed a marked decompensation of the frontal balance and a high degree of rigidity of the main curve and the compensatory curves after treatment with the VEPTR device. Because of this spontaneous autofusion of spinal segments, migration of the rib cradles and/or the laminar hook, and a change in the curve patterns, the final fusion had to be longer in all patients than the primary deformity would have intended. CONCLUSIONS: If an EOSD is treated with VEPTR, the curve progression and, in particular, the development of a high thoracic hyperkyphosis or rotation of the main curve should be critically observed. Autofusion of ribs and vertebral bodies may make the final correction spondylodesis even more challenging and risky for the patient and the end result less satisfactory. PMID- 27196003 TI - Disruption of Locomotion in Response to Hindlimb Muscle Stretch at Acute and Chronic Time Points after a Spinal Cord Injury in Rats. AB - After spinal cord injury (SCI) muscle contractures develop in the plegic limbs of many patients. Physical therapists commonly use stretching as an approach to avoid contractures and to maintain the extensibility of soft tissues. We found previously that a daily stretching protocol has a negative effect on locomotor recovery in rats with mild thoracic SCI. The purpose of the current study was to determine the effects of stretching on locomotor function at acute and chronic time points after moderately severe contusive SCI. Female Sprague-Dawley rats with 25 g-cm T10 contusion injuries received our standard 24-min stretching protocol starting 4 days (acutely) or 10 weeks (chronically) post-injury (5 days/week for 5 or 4 weeks, respectively). Locomotor function was assessed using the BBB (Basso, Beattie, and Bresnahan) Open Field Locomotor Scale, video-based kinematics, and gait analysis. Locomotor deficits were evident in the acute animals after only 5 days of stretching and increasing the perceived intensity of stretching at week 4 resulted in greater impairment. Stretching initiated chronically resulted in dramatic decrements in locomotor function because most animals had BBB scores of 0-3 for weeks 2, 3, and 4 of stretching. Locomotor function recovered to control levels for both groups within 2 weeks once daily stretching ceased. Histological analysis revealed no apparent signs of overt and persistent damage to muscles undergoing stretching. The current study extends our observations of the stretching phenomenon to a more clinically relevant moderately severe SCI animal model. The results are in agreement with our previous findings and further demonstrate that spinal cord locomotor circuitry is especially vulnerable to the negative effects of stretching at chronic time points. While the clinical relevance of this phenomenon remains unknown, we speculate that stretching may contribute to the lack of locomotor recovery in some patients. PMID- 27196005 TI - PEEK Cages in Lumbar Fusion: Mid-term Clinical Outcome and Radiologic Fusion. AB - STUDY DESIGN: Historical cohort analysis. OBJECTIVE: Evaluation of mid-term clinical outcome and radiologic fusion in patients treated with a polyetheretherketone (PEEK) cage. SUMMARY OF BACKGROUND DATA: Anterior lumbar interbody fusion can be a good alternative in chronic low back pain when conservative treatment fails. Although titanium alloy cages give good fusion rates, disadvantages are the subsidence of the cage in the adjacent vertebrae and problematic radiologic evaluation of fusion. PEEK cages such as the Synfix-LR cage (Synthes, Switzerland) should overcome this. METHODS: From December 2004 until August 2007, 95 patients (21 double-level and 74 single-level) with degenerative disk disease from L3-S1 were operated by a single surgeon. The number of reoperations was counted. Radiologic fusion on computed tomography scan was scored with a new scoring system by an independent skeletal radiologist and orthopedic surgeon. Intraobserver agreement and specificity were assessed. Clinical improvement was measured by the Oswestry Disability Index score. The median duration of clinical follow-up was 47.7 months (range 29.9-61.6). RESULTS: In total, 26 patients were reoperated after a median period of 17.6 months (range 6.7-46.9) of the initial surgery. Of the 26 patients, 23 patients (18 single level and 5 double-level) were reoperated for symptomatic pseudarthrosis. A moderate agreement (kappa=0.36) and a specificity of 70% and 37% for the radiologist and orthopedic surgeon, respectively, were found for scoring bony bridging. The Oswestry Disability Index score improved after initial surgery; however, reoperated patients reported a significantly lower improvement. CONCLUSIONS: A high number of reoperations after an anterior lumbar interbody fusion procedure with the Synfix-LR cage were found, mainly because of symptomatic pseudarthrosis. The absence of posterior fixation in combination with lower stiffness and the hydrophobic characteristics of PEEK probably lead to insufficient initial stability, creating suboptimal conditions for bony bridging, and thus solid fusion. The proposed ease of the evaluation of radiologic fusion could not be supported. Clinicians should be alert on pseudarthrosis when patients treated with the Synfix-LR cage presented with persisted or aggravated complaints. PMID- 27196007 TI - Emotional Disorders and the Wounded Self. PMID- 27196006 TI - Influenza vaccination in the Americas: Progress and challenges after the 2009 A(H1N1) influenza pandemic. AB - BACKGROUND: There has been considerable uptake of seasonal influenza vaccines in the Americas compared to other regions. We describe the current influenza vaccination target groups, recent progress in vaccine uptake and in generating evidence on influenza seasonality and vaccine effectiveness for immunization programs. We also discuss persistent challenges, 5 years after the A(H1N1) 2009 influenza pandemic. METHODS: We compiled and summarized data annually reported by countries to the Pan American Health Organization/World Health Organization (PAHO/WHO) through the WHO/UNICEF joint report form on immunization, information obtained through PAHO's Revolving Fund for Vaccine Procurement and communications with managers of national Expanded Programs on Immunization (EPI). RESULTS: Since 2008, 25 countries/territories in the Americas have introduced new target groups for vaccination or expanded the age ranges of existing target groups. As of 2014, 40 (89%) out of 45 countries/territories have policies established for seasonal influenza vaccination. Currently, 29 (64%) countries/territories target pregnant women for vaccination, the highest priority group according to WHO's Stategic Advisory Group of Experts and PAHO/WHO's Technical Advisory Group on Vaccine preventable Diseases, compared to only 7 (16%) in 2008. Among 23 countries reporting coverage data, on average, 75% of adults >=60 years, 45% of children aged 6-23 months, 32% of children aged 5-2 years, 59% of pregnant women, 78% of healthcare workers, and 90% of individuals with chronic conditions were vaccinated during the 2013-14 Northern Hemisphere or 2014 Southern Hemisphere influenza vaccination activities. Difficulties however persist in the estimation of vaccination coverage, especially for pregnant women and persons with chronic conditions. Since 2007, 6 tropical countries have changed their vaccine formulation from the Northern to the Southern Hemisphere formulation and the timing of their campaigns to April-May following the review of national evidence. LAC countries have also established an official network dedicated to evaluating influenza vaccines effectiveness and impact. CONCLUSION: Following the A(H1N1)2009 influenza pandemic, countries of the Americas have continued their efforts to sustain or increase seasonal influenza vaccine uptake among high risk groups, especially among pregnant women. Countries also continued strengthening influenza surveillance, immunization platforms and information systems, indirectly improving preparedness for future pandemics. Influenza vaccination is particularly challenging compared to other vaccines included in EPI schedules, due to the need for annual, optimally timed vaccination, the wide spectrum of target groups, and the limitations of the available vaccines. Countries should continue to monitor influenza vaccination coverage, generate evidence for vaccination programs and implement social communication strategies addressing existing gaps. PMID- 27196009 TI - Cognitive Hypnotherapy for Accessing and Healing Emotional Injuries for Anxiety Disorders. AB - Although anxiety disorders on the surface may appear simple, they often represent complex problems that are compounded by underlying factors. For these reasons, treatment of anxiety disorders should be individualized. This article describes cognitive hypnotherapy, an individual comprehensive treatment protocol that integrates cognitive, behavioral, mindfulness, psychodynamic, and hypnotic strategies in the management of anxiety disorders. The treatment approach is based on the self-wounds model of anxiety disorders, which provides the rationale for integrating diverse strategies in the psychotherapy for anxiety disorders. Due to its evidence-based and integrated nature, the psychotherapy described here provides accuracy, efficacy, and sophistication in the formulation and treatment of anxiety disorders. This model can be easily adapted to the understanding and treatment of other emotional disorders. PMID- 27196008 TI - Anxiety and the Wounded Self. AB - The self-wounds model of anxiety disorders based on the work of Wolfe (2005, 2006) is delineated here. The focal point of this model is the concept of wounded self or early unresolved emotional injuries. According to this view, anxiety disorders represent a chronic struggle with painful experiences. These emotional experiences are driven by two interrelated layers of psychological processes which arise from the wounded self. While the first layer of this process entails conscious awareness of symptoms resulting from cognitive distortions, the second layer comprises implicit or unconscious interpretations of what the symptoms mean to the patient. This article describes the components of the self-wounds model of anxiety disorders, which offers an integrative perspective on the development, onset, maintenance, and treatment of anxiety disorders. This model can be easily adapted to the understanding and treatment of other emotional disorders. PMID- 27196011 TI - The Wounded Self in Trauma Treatment. AB - The potential role of hypnosis in the treatment of trauma is both venerable and underappreciated. This article underscores the importance of the wounded-self concept by proposing a Kohutian perspective complimentary to the cognitively driven model of Alladin (2014a, 2014b) discussed elsewhere in this issue. It explores selected topics that demonstrate (1) the importance of considering the wounds to the sense of self experienced by trauma victims and their implications for individualization of treatment in planning a psychotherapy; (2) the possibility of enhancing access to memories using shame alleviating techniques with minimal suggestive properties; (3) the use of hypnosis to facilitate less disruptive processing of traumatic materials; and (4) the importance of hypnosis in enhancing the safety of the trauma patient between sessions. Absent contraindications, the circumspect use of hypnosis as a facilitator of trauma treatment deserves consideration for inclusion in the mainstream of contemporary trauma treatment. PMID- 27196010 TI - Attachment-Focused Psychotherapy and the Wounded Self. AB - The concept of the "wounded self" (Wolfe, 2005) offers an integrative theoretical framework for self-wounds and their developmental origins. Alladin (2013, 2014, 2016) integrated hypnotherapy into this model to comprehensively address the unconscious protective mechanisms and maladaptive conscious cognitive strategies of the wounded self. The purpose of this article is to propose how an attachment focused psychotherapy could be utilized in working with the wounded self. With its emphasis on developmental maturation through the frame of the attachment relationship, attachment theory is well-positioned to offer conceptual and treatment insights in treating the wounded self. E. B. Spiegel's (2016) attunement, representation, and mentalization approach to attachment-focused psychotherapy described how hypnosis can be utilized across attachment processes of attunement, representation, and mentalization toward structural maturation and developmental repair of patients with histories of complex relational trauma. In this article, the attunement, representation, and mentalization attachment approach and associated interventions are further explicated in the treatment of self-wounds in the borderline and narcissistic spectrums of personality organization. These principles of conceptualization and treatment interventions are then applied in a case example. PMID- 27196012 TI - Resistance to Healing the Wounded Self: A Psychodynamic Rationale for a Targeted Treatment. AB - The purpose of this article is to shed light on the psychodynamic complexities of the resistance encountered in treating the wounded self. Conceptualized on the basis of ego state therapy it offers a rationale for the use of precision targeted abreactive hypnosis to treat these patients. Grounded in evidence-based efficacy research, the authors also briefly explain how to target treatment in wounded-self patients. PMID- 27196013 TI - Resistance and the Wounded Self: Self-Protection in Service of the Ego. AB - This article describes the phenomenon of therapeutic resistance and reactance from the perspective of the wounded self. The concept of the wounded self is first presented as it is applied to anxiety and depression and then extended to anger applications. The wounded self can be seen as deeply embedded in human cognitive structures (or core beliefs) of tacit knowledge. The operation of tacit knowledge is then described in everyday life as well as in the therapeutic process. Then there is a discussion of the role of resistance and psychological reactance in psychotherapy with implications for the therapeutic alliance. Finally, a case of a resistant client with anger issues using the cognitive hypnotherapy model is presented. PMID- 27196014 TI - The Wounded Healer: From the Other Side of the Couch. AB - While concern for the "wounds" of the patient are paramount in clinical practice, there is both historical and contemporary literature on wounding in the professional. In what follows, these perspectives are presented. Issues related to transference/counter-transference, the "wounded healer," vicarious traumatization, nocebo potential in informed consent, and the use of treatment as crucible for one's own development as clinician are discussed. PMID- 27196015 TI - Impact of a rapid multiplex polymerase chain reaction blood culture identification technology on outcomes in patients with vancomycin-resistant Enterococcal bacteremia. AB - BACKGROUND: Early appropriate antibiotic selection is associated with favorable clinical outcomes. We evaluated the clinical impact of rapid detection of vancomycin-resistant Enterococcal bacteremia (VREB) by the FilmArray blood culture identification (BCID) panel coupled with antimicrobial stewardship program (ASP) interventions. METHODS: Hospitalized adult patients with VREB identified by conventional methods (CM) were compared to patients with VREB identified by BCID. Real time alerts of BCID results were provided to the ASP for intervention. Outcomes were compared between groups. RESULTS: Sixty-eight patients with VREB were included (CM, n = 45; BCID, n = 23). No significant differences in demographics, pre-existing conditions, or clinical characteristics were observed. Significant reductions were demonstrated between CM and BCID groups in median hours to organism identification (47.7 versus 18.2, p < 0.001), to identification of vancomycin resistance from time of culture positivity (50.1 versus 1.2, p < 0.001), and time to effective therapy (50.3 versus 20.8, p < 0.001). Differences between CM and BCID did not reach statistical significance for mortality (35.6% versus 26.1%), 30-day readmission rate (31.0% versus 17.6%), intensive care length of stay [LOS] (8.0 versus 7.0 days), post-culture LOS (14.6 versus 14.1 days) or median hospital costs per patient ($95,826 versus $53,195). CONCLUSIONS: In patients with VREB, rapid organism and resistance detection by the BCID panel with ASP intervention significantly reduced time to initiation of effective therapy by over 24 hours. Non-significant improvements in clinical outcomes were observed. Additional studies are needed to determine the full implications of BCID technology on patient outcome. PMID- 27196016 TI - Deletion of Opg Leads to Increased Neovascularization and Expression of Inflammatory Cytokines in the Lumbar Intervertebral Disc of Mice. AB - STUDY DESIGN: Neovascularization and expression of inflammatory cytokines were examined in Osteoprotegerin (Opg) knockout (KO) mice that show intervertebral disc (IVD) degeneration. OBJECTIVE: The aim of this study was to clarify the pathological changes in lumbar IVD degeneration in Opg KO mice. SUMMARY OF BACKGROUND DATA: Osteoporosis is a controversial risk factor for IVD degeneration. Deletion of Opg resulted in IVD degeneration in mice. Neovascularization and inflammatory cytokines are key factors in IVD degeneration. METHODS: Opg KO mice and their wild-type (WT) littermates were euthanized. Lumbar IVDs were harvested. Safranin O/Fast Green staining was performed to examine the pathological changes. Microcomputed tomographic (micro CT) analysis was performed to determine the structural changes at the junction of lumbar IVD cartilage and vertebrae. Tartrate-resistant acid phosphatase (TRAP) staining was performed to evaluate osteoclast formation. Protein expression of vascular endothelial growth factor A (VEGF-A), CD31, VE-cadherin, CD 34, interleukin-1beta (IL-1beta), and tumor necrosis factors alpha (TNF-alpha) were analyzed by immunohistochemistry (IHC) assays. Gene expressions of IL-1beta, IL 6, and TNF-alpha were analyzed by real-time polymerase chain reaction (RT-PCR). RESULTS: In 12-week-old Opg KO mice, new bone was formed in the endplate cartilage of lumbar IVDs and this became more obvious in 24-week-old Opg KO mice. Three-dimensional (3D) MUCT reconstruction analyses showed that the edges of the L4 and L5 vertebrae were rugged with bone marrow cavities in it. Protein expression of VEGF-A, CD31, VE-cadherin, and CD34 was increased in the endplate and growth plate of lumbar IVDs of Opg KO mice. Gene expression of IL-1beta, IL 6, and TNF-alpha as well as protein expression of IL-1beta and TNF-alpha were highly expressed in the lumbar IVDs of Opg KO mice. CONCLUSION: Deletion of Opg leads to increased neovascularization and expression of inflammatory cytokines in the lumbar disc in Opg KO mice, which may play important roles in IVD degeneration. LEVEL OF EVIDENCE: N/A. PMID- 27196017 TI - Predicting Cervical Alignment Required to Maintain Horizontal Gaze Based on Global Spinal Alignment. AB - STUDY DESIGN: A retrospective cohort. OBJECTIVE: The aim of this study was to investigate the cervical alignment necessary for the maintenance of horizontal gaze that depends on underlying thoracolumbar alignment. SUMMARY OF BACKGROUND DATA: Cervical Sagittal Curve (CC) is affected by thoracic and global alignment. Recent studies suggest large variability in normative CC ranging from lordotic to kyphotic alignment. No previous studies have assessed the effect of global spinal alignment on CC in maintenance of horizontal gaze. METHODS: Patients without previous history of spinal surgery and able to maintain their horizontal gaze while undergoing full body imaging were included. Patients were stratified on the basis of thoracic kyphosis (TK) into (<30, 30-40, 40-50, and >50) and then by SRS Schwab sagittal vertical axis (SVA) modifier into (posterior alignment SVA <0, aligned 0-50, and malaligned >50 mm). Cervical alignment was assessed among SVA grade in TK groups. Stepwise linear regression analysis was applied on random selection of 60% of the population. A simplified formula was developed and validated on the remaining 40%. RESULTS: In each TK group (n = 118, 137, 125, 197), lower CC (C2-C7) was significantly more lordotic by increased Schwab SVA grade. T1 slope and cervical SVA significantly increased with increased thoracolumbar (C7-S1) SVA. Upper CC (C0-C2) and mismatch between T1 slope and CC (T1-CL) were similar. Regression analysis revealed LL minus TK (LL-TK) as an independent predictor (r = 0.640, r = 0.410) with formula: CC = 10- (LL-TK)/2. Validation revealed that the absolute difference between the predicted CC and the actual CC was 8.5 degrees . Moreover, 64.2% of patients had their predicted C2-C7 values within 10 degrees of the actual CC. CONCLUSION: Cervical kyphosis may represent normal alignment in a significant number of patients. However, in patients with SVA >50 and greater thoracic kyphosis, cervical lordosis is needed to maintain the gaze. Cervical alignment can be predicted from underlying TK and lumbar lordosis, which may be clinically relevant when considering correction for thoracolumbar or cervical deformityLevel of Evidence: 3. PMID- 27196018 TI - Lower Lumbar Segmental Arteries Can Intersect Over the Intervertebral Disc in the Oblique Lateral Interbody Fusion Approach With a Risk for Arterial Injury: Radiological Analysis of Lumbar Segmental Arteries by Using Magnetic Resonance Imaging. AB - STUDY DESIGN: A retrospective radiological study on vascular anatomy. OBJECTIVE: The aim of this study was to evaluate the anatomical and radiological features of lumbar segmental arteries with respect to the surgical field of the oblique lateral interbody fusion (OLIF) approach by using magnetic resonance imaging (MRI). SUMMARY OF BACKGROUND DATA: OLIF surgery restores disc height and enables indirect decompression of narrowed spinal canals through an oblique lateral approach to the spine, by using a specially designed retractor. In a minimal surgical field, injuring segmental arteries can cause massive hemorrhage. METHODS: We reviewed 272 lumbar MRIs. In the sagittal images, the intersection of one-third of the anterior and median lines of the intervertebral disc (IVD) was considered the center of the virtually installed OLIF retractor. The cephalad/caudal distances from the center and branch angles of segmental arteries to the longitudinal axes of the aorta were measured to determine whether the segmental arteries run into the surgical area. Statistical significance was set at P < 0.05. RESULTS: The branch angles of segmental arteries were significantly acute (<=90 degrees ) in L1-L3 arteries and significantly blunt (>90 degrees ) in L4 and L5 arteries. The average distance to the center of the caudal adjacent IVD was significantly larger, and there were generally low possibilities for the existence of segmental arteries below half of the vertebral height, where the surgeons can install fixation pins with ease and safety. Among the lumbar segmental arteries, L5 showed specific characteristics with significant deviation, a four times (4.1% vs. L1-L3 segmental arteries) higher adjacency rate, and a two-fifth (38.6% vs. 100%) lower existence rate. CONCLUSION: Segmental arteries can be involved in the surgical field of OLIF especially in the lower lumbar spine level of L4 and L5 arteries, which can directly run across IVDs. L5 segmental arteries can also be iliolumbar arteries that have an abnormal trajectory by nature. LEVEL OF EVIDENCE: 4. PMID- 27196019 TI - Morbid Obesity and Lumbar Fusion in Patients Older Than 65 Years: Complications, Readmissions, Costs, and Length of Stay. AB - STUDY DESIGN: Retrospective database review. OBJECTIVE: The aim of this study was to determine how both morbid obesity (body mass index [BMI] >=40) and obesity (BMI 30-39.9) modify 90-day complication rates and 30-day readmission rates following 1- to 2-level, primary, lumbar spinal fusion surgery for degenerative pathology in an elderly population. SUMMARY OF BACKGROUND DATA: In the United States, both obese and elderly patients are known to have increased risk of complication, yet both demographics are increasingly undergoing elective lumbar spine surgery. METHODS: Medicare data from 2005 to 2012 were queried for patients who underwent primary 1- to 2-level posterolateral lumbar fusion for degenerative pathology. Elderly patients undergoing elective surgery were selected and separated into three cohorts: morbidly obese (BMI >=40; n = 2594), obese (BMI >=30, < 40] (n = 5534), and nonobese controls (n = 48,210). Each pathologic cohort was matched to a unique subcohort from the control population. Ninety-day medical and surgical complication rates, 30-day readmission rates, length of stay (LOS), and hospital costs were then compared. RESULTS: Both morbidly obese and obese patients had significantly higher odds of experiencing any one major medical complication (odds ratio [OR] 1.79; P < 0.0001 and OR 1.32; P < 0.0001, respectively). Wound infection (OR 3.71; P < 0.0001 and OR 2.22; P < 0.0001) and dehiscence (OR 3.80; P < 0.0001 and OR 2.59; P < 0.0001) rates were increased in morbidly obese and obese patients, respectively. Thirty-day readmissions, length of stay, and in-hospital costs were increased, with patients with morbid obesity incurring charges almost $8000 greater than controls. CONCLUSION: Patients with both obesity and morbid obesity are at significantly increased risk of major medical complications, wound complications, and 30-day readmissions. Additionally, both groups of patients have significantly increased LOS and hospital costs. Both obese and morbidly obese patients should be appropriately counseled of these risks and must be carefully selected to reduce postoperative morbidity. LEVEL OF EVIDENCE: 3. PMID- 27196021 TI - Evolution of Muscles Dysfunction From Myofascial Pain Syndrome Through Cervical Disc-Root Conflict to Degenerative Spine Disease. AB - STUDY DESIGN: Comparative clinical and neurophysiological study in three groups of patients with general diagnosis of neck pain. OBJECTIVE: To determine symptoms of muscles dysfunction in patients with myofascial pain syndrome, disc-root conflict, and degenerative changes at cervical spine. SUMMARY AND BACKGROUND DATA: The explanation for cervical pain origin should be based on results from chosen clinical and neurophysiological studies in correlation with neuroimaging findings. METHODS: Three subgroups of patients (N = 60 each) with certain symptoms were examined. Clinical evaluation included examination of pain intensity in VAS scale, muscle strength in Lovett scale, evaluation of reflexes, Spurling test, assessment of active trigger points (TRPs), and superficial sensory perception. Neurophysiological testing included surface electromyography at rest (rEMG) and during maximal contraction (mcEMG) as well as electroneurography (ENG). RESULTS: The greatest pain intensity with its decentralization phenomenon occurred in patients with disc-root conflict. Significant decrease of muscle strength was detected in trapezius muscle in myofascial pain syndrome subgroup. Weakness of abductor pollicis brevis muscle in patients with disc-root conflict differed them from patients with myofascial pain syndrome (P = 0.05). Patients with disc-root conflict and degenerative spine disease showed differences (P = 0.03) in reflexes evoked from triceps brachii. Positive Spurling symptom was most common (56.7%) in disc-root conflict subgroup. TRPs in trapezius muscle were found in all patients with myofascial pain syndrome. Results of rEMG amplitude measurements differed patients at P = 0.05. Only mcEMG recording from abductor pollicis brevis muscle allows for their clear cut differentiation. ENG studies showed abnormalities in patients with disc-root conflict and degenerative spine disease (P from 0.05 to 0.02). Positive correlation of VAS, TRPs, and rEMG as well as Lovett scores, mcEMG, and ENG results was found. CONCLUSION: Only applying several clinical and neurophysiological tests together makes it possible to differentiate patients with different etiological reasons of pain at cervical spine. LEVEL OF EVIDENCE: 4. PMID- 27196020 TI - Lumbar Degenerative Spondylolisthesis: Changes in Surgical Indications and Comparison of Instrumented Fusion With Two Surgical Decompression Procedures. AB - STUDY DESIGN: Single-center retrospective case series. OBJECTIVE: To compare outcomes of instrumented fusion and two methods of decompression for degenerative spondylolisthesis. SUMMARY OF BACKGROUND DATA: There is no consensus on the surgical indications or optimum techniques for lumbar degenerative spondylolisthesis. METHODS: We analyzed the data of 140 patients treated by fusion (n = 80; mean follow-up, 77.9 months) or decompression (n = 60; mean follow-up, 38.0 months) and examined changes in surgical indications over a 12 year period. We compared the outcomes of instrumented fusion with the outcomes of two decompression techniques, the first employing a unilateral approach for bilateral decompression and the second employing a bilateral approach for contralateral decompression, with contralateral foraminal decompression as needed. Postoperative evaluation was made at the final follow-up visit beginning in 2007 by analyzing patient interviews and neurological examination data. We compared results with the Japanese Orthopedic Association symptom score before surgery and at final follow-up. RESULTS: Surgical indications for fusion narrowed over time, with fusion used less frequently and decompression used more frequently. Similar decreases in clinical symptoms, including low back pain, were achieved with all methods. In the decompression groups, preoperative slip distance and instability, and postoperative slip progression or development of instability, did not correlate significantly with clinical outcome. Slip progression occurred in 8 of 10 levels in patients with preoperative translation >=5 mm, but these patients showed no increase in instability, defined as translation >= 2 mm, at final follow-up. CONCLUSION: Our findings raise a question about the value of the radiologic criteria for performing fusion used in the late period, namely translation >=5 mm and/or rotation >= 10 degrees . If discogenic pain is excluded, decompression alone may be suitable even for patients with severe low back pain and translation >=5 mm. LEVEL OF EVIDENCE: 4. PMID- 27196022 TI - Impact of Race and Insurance Status on Surgical Approach for Cervical Spondylotic Myelopathy in the United States: A Population-Based Analysis. AB - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The aim of the study was to assess factors potentially impacting the operative approach chosen for cervical spondylotic myelopathy (CSM) patients on a nationwide level. SUMMARY OF BACKGROUND DATA: CSM is one of the most common spinal disorders treated by spine surgeons, with operative management consisting of three approaches: anterior only, posterior-only, or combined anterior-posterior. It is unknown whether the operative approach used differs based on patient demographics and/or insurance status. METHODS: The nationwide inpatient sample from 2001 to 2010 was used for analysis. Admissions having a diagnosis code of 721.1 and a primary procedure code of 81.02/81.03, 81.32/81.33, 81.02/81.03, or 81.32/81.33 (combined anterior and posterior fusion/refusion at C2 or below), and 3.09 (decompression of the spinal canal including laminoplasty) were included. Analysis was adjusted for several variables including patient age, race, sex, primary payer for care, and admission source/type. RESULTS: Multivariate analyses revealed that non-white race (black [odds ratio, OR = 1.39; 95% confidence interval, CI = 1.32-1.47; P < 0.0001], Hispanic [OR = 1.51; 95% CI = 1.38-1.66; P < 0.0001], Asian/Pacific Islander [OR = 1.40; 95% CI = 1.15-1.70; P = 0.0007], Native American [OR = 1.33; 95% CI = 1.02-1.73; P = 0.037]) and increasing age (OR = 1.03; P < 0.0001) were predictive of receiving posterior-only approaches. Female sex (OR = 1.39; 95% CI = 1.34-1.43; P < 0.0001), private insurance (OR = 1.19; 95% CI = 1.14-1.25; P < 0.0001), and nontrauma center admission type (OR = 1.29-1.39; 95% CI = 1.16-1.56; P < 0.0001) were independently predictive of increased likelihood of receiving an anterior-only approach. Hispanic race (OR = 1.35; 95% CI = 1.14-1.59; P = 0.0004) and admission source (another hospital [OR = 1.65; 95% CI = 1.20-2.27; P = 0.0023], other health facility [OR = 1.68; 95% CI = 1.13-2.51; P = 0.011]) were the only variables predictive of increased combined anterior-posterior approaches; Native American race (OR = 0.32; 95% CI = 0.13-0.78; P = 0.013) decreased the likelihood of a combined anterior-posterior approach. CONCLUSION: Private insurance status, female sex, and white race independently predict receipt of anterior-only CSM approaches, whereasd non-white race (black, hispanic, Asian/Pacific Islander, Native American) and nonprivate insurance predict receiving posterior-only CSM approaches. Given recent literature demonstrating posterior-only approaches as predictive of increased mortality in CSM (Kaye et al, 2015), our findings indicate that for CSM patients, non-white race may significantly increase mortality risk, whereas private insurance status may significantly decrease the risk of mortality. Further prospective study will be needed to more definitively address these issues. LEVEL OF EVIDENCE: 3. PMID- 27196023 TI - Function and Clinical Symptoms are the Main Factors that Motivate Thoracolumbar Adult Scoliosis Patients to Pursue Surgery. AB - STUDY DESIGN: A retrospective two-cohort comparative analysis of data collected prospectively in an adult deformity multicenter database. OBJECTIVE: The aim of this study was to define the radiographic and clinical parameters that motivate adult thoracolumbar (TL) scoliosis patients to undergo surgery. SUMMARY OF BACKGROUND DATA: TL curves are a primary concern in adulthood, and it is necessary to establish why patients are motivated to seek surgical intervention. METHODS: Patients with only main TL/lumbar (TL/L) idiopathic curves were included, defined as Schwab type L curves and Schwab type D curves in which thoracic curves were <40 degrees and the difference between the TL/L-MT Cobb was >=15 degrees . Demographic data, health-related quality of life (HRQOL) questionnaires, and 14 different radiological preoperative parameters were assessed. Surgical versus conservative cohorts were compared with the Student t test, Chi-square, and the Mann-Whitney U test. RESULTS: A total of 184 patients met the inclusion criteria. Ninety-four were treated conservatively (C), while 90 underwent surgery (S). No differences were found between groups in terms of demographic or radiographic preoperative data. Age (C: 57.5 +/- 18 vs. S: 54.2 +/ 18 yr; P = 0.18), coronal TL/L Cobb (C: 52.3 degrees +/- 15 vs. S: 50.6 degrees +/- 13; P = 0.61), and sagittal alignment (SVA C: 3.1 cm +/- 5.7 vs. S: 4.9 cm +/- 6.4; P = 0.054) were similar. No differences were found in pelvic parameters (pelvic incidence, pelvic tilt, sacral slope), apical translation, coronal balance, lumbar rotatory subluxation, or lumbar lordosis. However, significant differences were found in HRQOL questionnaires. Surgical patients initially had worse COMI scores (C: 4.6 +/- 2.3 vs. S: 6 +/- 2.3; P = 0.001), worse ODI scores (C: 27.7 +/- 16 vs. S: 38.9 +/- 20; P = 0.000), worse SF-36 physical (C: 40.9 +/- 8.5 vs. S: 36 +/- 9.5; P = 0.001) and mental scores (C: 45.8 +/- 12 vs. S: 42.2 +/- 11.8; P = 0.032), and worse SRS-22 scores in all domains with mean values under 3.1 points (range = 2.4-3.1). In both SF-36 physical and SRS-22 function, differences between groups were higher than the minimum clinically important difference. CONCLUSION: After analyzing a large multicenter database, we found that only clinical factors-particularly function impairment-motivated adult TL scoliosis patients to undergo surgery. Demographic and radiographic parameters did not seem to influence decision-making. LEVEL OF EVIDENCE: 3. PMID- 27196025 TI - Comparison of Tuberculous and Brucellar Spondylitis on Magnetic Resonance Images. AB - STUDY DESIGN: Retrospective cross-sectional study. OBJECTIVE: To investigate the differences between tuberculous spondylitis (TS) and brucellar spondylitis (BS) on magnetic resonance images (MRI). SUMMARY OF BACKGROUND DATA: Both TS and BS are common spinal affections and can cause deformities and permanent neurologic deficiencies without prompt diagnosis and treatment. However, differentiating the types of spondylitis clinically and radiographically is challenging. Despite the diagnosis studies on spine infection throughout the literature, the outcome has not been established. Our study about the different characteristics between TS and BS on MRI may be helpful. METHODS: Eighteen patients with TS and 26 with BS were included in this study. MRI images were obtained and analyzed. For statistical analysis, the chi test was performed. Statistical significance was defined as P < 0.05. RESULTS: There were statistically significant differences between TS and BS on the MRI images: (i) subligamentous spread to three or more vertebral levels [TS 54% (7/13) vs. BS 8% (1/12)]; (ii) subligamentous spread to fewer than three vertebral levels [23% (3/13) vs. 58% (7/12)]; (iii) thoracic spine involvement [50% (9/18) vs. 4% (1/26)]; and lumbar spine involvement [22% (4/18) vs. 77% (20/26)]; (iv) abnormal signal from the vertebral disc on T2 weighted images [33% (7/21) vs. 85% (30/35)]; (v) focal or fan-shaped hyperintense signals on middle sagittal fat-suppressed weighted images [14% (7/50) vs. 50% (31/62)] and especially fan-shaped hyperintense signal [0% (0/50) vs. 23% (14/62)]; (vi) spinal kyphosis [22% (11/50) vs. 3% (2/62)]; (vii) vertebral collapse [42% (21/50) vs. 2% (1/62)]; (viii) peridiscal bone destruction [22% (11/50) vs. 44% (27/62)]; and (ix) psoas abscesses [6% (3/50) vs. 0% (0/62)]. CONCLUSION: MRI is a sensitive imaging technique and can clearly define the different features between TS and BS, so it should be the first choice for imaging in the diagnosis of spondylodiscitis. LEVEL OF EVIDENCE: 4. PMID- 27196026 TI - Effect of Polyether Ether Ketone on Therapeutic Radiation to the Spine: A Pilot Study. AB - STUDY DESIGN: Cadaveric model. OBJECTIVES: To compare the effect of PEEK versus conventional implants on scatter radiation to a simulated tumor bed in the spine SUMMARY OF BACKGROUND DATA.: Given the highly vasculature nature of the spine, it is the most common place for bony metastases. After surgical treatment of a spinal metastasis, adjuvant radiation therapy is typically administered. Radiation dosing is primarily limited by toxicity to the spinal cord. The scatter effect caused by metallic implants decreases the accuracy of dosing and can unintentionally increase the effective dose seen by the spinal cord. This represents a dose-limiting factor for therapeutic radiation postoperatively. METHODS: A cadaveric thorax specimen was utilized as a metastatic tumor model with two separate three-level spine constructs (one upper thoracic and one lower thoracic). Each construct was examined independently. All four groups compared included identical posterior instrumentation. The anterior constructs consisted of either: an anterior polyether ether ketone (PEEK) cage, an anterior titanium cage, an anterior bone cement cage (polymethyl methacrylate), or a control group with posterior instrumentation alone. Each construct had six thermoluminescent detectors to measure the radiation dose. RESULTS: The mean dose was similar across all constructs and locations. There was more variability in the upper thoracic spine irrespective of the construct type. The PEEK construct had a more uniform dose distribution with a standard deviation of 9.76. The standard deviation of the others constructs was 14.26 for the control group, 19.31 for the titanium cage, and 21.57 for the cement (polymethyl methacrylate) construct. CONCLUSION: The PEEK inter-body cage resulted in a significantly more uniform distribution of therapeutic radiation in the spine when compared with the other constructs. This may allow for the application of higher effective dosing to the tumor bed for spinal metastases without increasing spinal cord toxicity with either fractionated or hypofractionated radiotherapy. LEVEL OF EVIDENCE: N/A. PMID- 27196027 TI - Acute Stress and Perceptual Load Consume the Same Attentional Resources: A Behavioral-ERP Study. AB - Stress and perceptual load affect selective attention in a paradoxical manner. They can facilitate selectivity or disrupt it. This EEG study was designed to examine the reciprocal relations between stress, load and attention. Two groups of subjects, one that performed the Trier Social Stress Test (TSST), and a control group, were asked to respond to a target letter under low and high perceptual load in the absence or presence of a distractor. In the control group, the distractor increased response times (RTs) for high and low load. In the TSST group, distractor increased RTs under low load only. ERPs showed that distractor's presentation attenuated early visual P1 component and shortened its latency. In the TSST group, distractor reduced P1 component under high load but did not affect its latency. Source localization demonstrated reduced activation in V1 in response to distractors presence in the P1 time window for the TSST group compared to the control group. A behavioral replication revealed that in the TSST group distractors were less perceived under high load. Taken together, our results show that stress and perceptual load affect selectivity through the early stages of visual processing and might increase selectivity in a manner that would block conscious perception of irrelevant stimuli. PMID- 27196028 TI - Asymptomatic Renal Pseudoaneurysm Following Laparoscopic Partial Nephrectomy. AB - A 66-year-old-woman underwent a laparoscopic left partial nephrectomy for a 3 cm partially exophytic tumor arising from the posterior interpolar region of the left kidney. Follow-up surveillance computed tomography 6 months following the surgery found an incidental 4 cm lesion in the left kidney that is avidly enhanced in the arterial phase, consistent with a renal pseudoaneurysm. She was completely asymptomatic. Renal pseudoaneurysm is a rare complication following minimally invasive nephron-sparing surgery and typically presents in the early postoperative period with gross hematuria. However, a large renal pseudoaneurysm may also present as an asymptomatic incidental finding and is amenable to angioembolization. PMID- 27196029 TI - Improvements in Patient-reported Sexual Function After Microsurgical Varicocelectomy. AB - OBJECTIVE: To evaluate whether varicocelectomy improves both serum testosterone and sexual function, as assessed by the Male Sexual Health Questionnaire (MSHQ). METHODS: A retrospective chart review of patients who have undergone varicocelectomy and had both pre- and postoperative MSHQ was performed. The MSHQ is a clinically validated questionnaire that assesses erectile function, ejaculatory function, and sexual satisfaction, with higher scores indicating better function. Clinical parameters pre and postvaricocelectomy were compared with paired t test. RESULTS: Thirty-four patients met study criteria. Seventeen patients (50%) presented for infertility, and the remaining 13 had symptomatic varicocele associated with hypogonadism. Average postsurgical follow-up was 20.6 +/- 12.5 months. The majority of men in the study had bilateral varicoceles and left grade III varicoceles. Significant improvements in the total MSHQ score (3.9 +/- 8.7, P = .027), the MSHQ erectile function (1.2 +/- 2.3, P = .007), and the MSHQ ejaculatory function (1.4 +/- 3.1, P = .018) domains were seen. Fifteen (44%) men saw improvement in their erectile function and 18 (53%) saw improvement in ejaculatory function. The improvement in serum testosterone was also significant (136.0 +/- 201.3 ng/dL, P = .007). CONCLUSION: Microsurgical repair of varicocele not only improves testosterone, but also improves patient-reported erectile and ejaculatory functions. Patients can confidently be counseled that varicocelectomy has the potential to improve sexual function along with serum testosterone. PMID- 27196030 TI - 30-Day Morbidity and Reoperation Following Midurethral Sling: Analysis of 8772 Cases Using a National Prospective Database. AB - OBJECTIVE: To determine 30-day complications, risk of readmission, and reoperation for midurethral slings (MUS). METHODS: The National Surgical Quality Improvement Program database from 2006 to 2013 was queried for MUS alone by excluding concurrent reconstructive, urologic, or gynecologic procedures. We assessed baseline characteristics, 30-day perioperative outcomes and 30-day readmission. Logistic regression analysis identified risk factors for the frequent complications. RESULTS: There were 8772 women who underwent MUS, of which 3830 (43.7%) and 4942 (56.3%) were performed by urologists and gynecologists, respectively. Patients of urologists were older, had higher frailty, and were more likely diabetic (all P < .05). Patients of gynecologists were more likely to have resident involvement compared to urologists (16.4% vs 11.2%, P < .001). Mean operative time was shorter for urologists compared to gynecologists (35.6 +/- 29.2 minutes vs 38.1 +/- 34.3 minutes, P < .001). The overall 30-day rate of any complication was 3.52%. Urinary tract infection (UTI) occurred in 2.2% vs 3.5% of the urologic and gynecologic patients, respectively (P=.001). After adjusting for frailty, body mass index, steroid use, age, operative time, and residency involvement, gynecologic performed surgery incurred an increased risk of UTI (OR 1.67, 95% CI 1.27-2.19; P=.001). Sixty-five (0.90%) patients were readmitted within 30 days, most commonly due to urinary symptoms. Sling revision for urinary obstruction occurred in 15 patients; 10 underwent repair of the bladder, urethra, or vagina. CONCLUSION: To our knowledge, we present the largest American cohort of MUS 30-day outcomes to date, stratified by specialty of performing surgeon. Overall, morbidity is low. UTI is the most common complication, and occurs at increased frequency for patients of gynecologists. PMID- 27196031 TI - Erastus B. Wolcott: A Pioneer in Renal Surgery and Frontier Medicine. PMID- 27196032 TI - Abstinence Time and Its Impact on Basic and Advanced Semen Parameters. AB - OBJECTIVE: To assess the effect of ejaculatory abstinence (EA) periods on routine and advanced sperm tests. METHODS: Men with normozoospermia provided semen samples after 1, 2, 5, 7, 9, and 11 days of abstinence. A standard semen analysis was performed on all samples. Each specimen was assessed for levels of reactive oxygen species (ROS) and sperm DNA fragmentation. Comparison was also made by grouping EA periods into short (1 day), recommended by World Health Organization (WHO) (2-7 days), and long (9-11 days). RESULTS: Semen volume (P < .001), sperm concentration (P < .001), and total sperm count (P < .001) increased significantly with abstinence length. Sperm DNA fragmentation was associated with the length of EA (P < .001). Both 1 and 2 days of EA had the least amount of DNA fragmentation (P < .001). Significant increase was seen in volume, pH, viscosity, total count, total motile sperm, and DNA fragmentation between short and recommended EA (P < .05), and between recommended and long EA (P < .05). Short EA had no detrimental impact on semen characteristics according to the 2010 WHO thresholds. CONCLUSION: Shortening of EA time is not detrimental to sperm quality in men with normozoospermia and is proposed as a method for reducing sperm DNA fragmentation. This strategy could help optimize sperm quality and the chances of natural and assisted conception. Accurate abstinence time should be considered when managing men with infertility problems with semen analyses even when it is within the recommended range. PMID- 27196033 TI - Cyclization of 4-Phenoxy-2-coumarins and 2-Pyrones via a Double C-H Activation. AB - Aryl-heteroaryl coupling via double C-H activation is a powerful transformation that avoids the installation of activating groups. A double C-H activation of privileged biological scaffolds, 2-coumarins and 2-pyrones, is reported. Despite the rich chemistry of these molecular frameworks, the yields are very good. Excellent regioselectivity was achieved on the pyrones. This methodology was applied to the synthesis of flemichapparin C in three steps. Isotope effect experiments were carried out, and a mechanism is proposed. PMID- 27196034 TI - A School Passport as Part of a Protocol to Assist Educational Reintegration After Medulloblastoma Treatment in Childhood. AB - BACKGROUND: Medulloblastoma is the most common malignant brain tumour in children and is treated with a combination of surgery, radiotherapy and chemotherapy. These children frequently experience long-term cognitive, social and physical sequelae, which significantly affect school reintegration. AIM: This study aimed to explore school-return experiences to create a more structured school reintegration protocol for children postmedulloblastoma. METHODS: A cohort of nine patients who had completed treatment and for whom full neuropsychometric data were available was included in the study (median time since diagnosis 8 years). Data were collected using qualitative parental questionnaires, semistructured interviews with teachers (n = 12) and healthcare professionals (HCPs) (n = 6) involved in their school reintegration. Thematic analysis was employed. A focus group with five HCPs was then used for data validation. RESULTS: This study uncovered the following four main subjects: (1) Information sharing; (2) education and empowerment (of educational professionals (EP) and parents); (3) communication between parents, HCPs and EPs; and (4) long-term difficulties. DISCUSSION: Implementation of a standardised protocol delivered within the structure of a school passport document would aid uniform follow-up. The proposed multistage protocol includes early communication and reintegration planning followed by meetings at school re-entry. Follow-up meetings are suggested to reduce information loss and reassess the child's needs. Hospital support at school transitions, inclusion of school data in long-term clinical follow-up and long-term rehabilitation are also recommended. Each stage would be supported by school passport documentation and would facilitate school and parental empowerment, paramount to the long-term sustainability of successful schooling. PMID- 27196036 TI - Generation of Small Single Domain Nanobody Binders for Sensitive Detection of Testosterone by Electrochemical Impedance Spectroscopy. AB - A phage display library of variable domain of the heavy chain only antibody or nanobody (Nb) was constructed after immunizing a bactrian camel with testosterone. With the smaller molecular size (15 kDa), improved solubility, good stability, high affinity, specificity, and lower immunogenicity, Nbs are a promising tool in the next generation of diagnosis and medical applications. Testosterone is a reproductive hormone, playing an important role in normal cardiac function and being the highly predictive marker for many diseases. Herein, a simple and sensitive immunosensor based on electrochemical impedance spectroscopy (EIS) and Nbs was successfully developed for the determination of testosterone. We successfully isolated the antitestosterone Nbs from an immune phage display library. Moreover, one of the Nbs was biotinylated according to in vivo BirA system, which showed the highest production yield and the most stable case. Further, the EIS immunosensor was set up for testosterone detection by applying the biotinylated antitestosterone Nb. As a result, the biosensor exhibited a linear working range from 0.05 to 5 ng mL(-1) with a detection limit of 0.045 ng mL(-1). In addition, the proposed immunosensor was successfully applied in determining testosterone in serum samples. In conclusion, the proposed immunosensor revealed high specificity of testosterone detection and showed as a potential approach for sensitive and accurate diagnosis of testosterone. PMID- 27196037 TI - Factors Influencing Communication with Doctors via the Internet: A Cross Sectional Analysis of 2014 HINTS Survey. AB - Based on Street's (2003) ecological framework of communication in medical encounters, this study examined personal, interpersonal, and media factors that could influence patients' use of the Internet to communicate with doctors. Results from data analysis of responses from the 2014 Health Information National Trends Survey showed that patient activation and ease of Internet access were two positive predictors of online doctor-patient communication. In addition, patients' trust in doctors positively moderated the relationships between patient activation and online doctor-patient communication, and between perceived health status and online doctor-patient communication. Finally, the quality of patients' past experiences communicating with doctors had a positive moderation effect on the association between health information seeking behavior and online doctor patient communication. Implications and limitations are discussed. PMID- 27196035 TI - TopoGromacs: Automated Topology Conversion from CHARMM to GROMACS within VMD. AB - Molecular dynamics (MD) simulation engines use a variety of different approaches for modeling molecular systems with force fields that govern their dynamics and describe their topology. These different approaches introduce incompatibilities between engines, and previously published software bridges the gaps between many popular MD packages, such as between CHARMM and AMBER or GROMACS and LAMMPS. While there are many structure building tools available that generate topologies and structures in CHARMM format, only recently have mechanisms been developed to convert their results into GROMACS input. We present an approach to convert CHARMM-formatted topology and parameters into a format suitable for simulation with GROMACS by expanding the functionality of TopoTools, a plugin integrated within the widely used molecular visualization and analysis software VMD. The conversion process was diligently tested on a comprehensive set of biological molecules in vacuo. The resulting comparison between energy terms shows that the translation performed was lossless as the energies were unchanged for identical starting configurations. By applying the conversion process to conventional benchmark systems that mimic typical modestly sized MD systems, we explore the effect of the implementation choices made in CHARMM, NAMD, and GROMACS. The newly available automatic conversion capability breaks down barriers between simulation tools and user communities and allows users to easily compare simulation programs and leverage their unique features without the tedium of constructing a topology twice. PMID- 27196048 TI - Evidence of a Cooler Continental Climate in East China during the Warm Early Cenozoic. AB - The early Cenozoic was characterized by a very warm climate especially during the Early Eocene. To understand climatic changes in eastern Asia, we reconstructed the Early Eocene vegetation and climate based on palynological data of a borehole from Wutu coal mine, East China and evaluated the climatic differences between eastern Asia and Central Europe. The Wutu palynological assemblages indicated a warm temperate vegetation succession comprising mixed needle- and broad-leaved forests. Three periods of vegetation succession over time were recognized. The changes of palynomorph relative abundance indicated that period 1 was warm and humid, period 2 was relatively warmer and wetter, and period 3 was cooler and drier again. The climatic parameters estimated by the coexistence approach (CA) suggested that the Early Eocene climate in Wutu was warmer and wetter. Mean annual temperature (MAT) was approximately 16 degrees C and mean annual precipitation (MAP) was 800-1400 mm. Comparison of the Early Eocene climatic parameters of Wutu with those of 39 other fossil floras of different age in East China, reveals that 1) the climate became gradually cooler during the last 65 million years, with MAT dropping by 9.3 degrees C. This cooling trend coincided with the ocean temperature changes but with weaker amplitude; 2) the Early Eocene climate was cooler in East China than in Central Europe; 3) the cooling trend in East China (MAT dropped by 6.9 degrees C) was gentler than in Central Europe (MAT dropped by 13 degrees C) during the last 45 million years. PMID- 27196049 TI - Dirofilaria in Humans, Dogs, and Vectors in Austria (1978-2014)-From Imported Pathogens to the Endemicity of Dirofilaria repens. AB - BACKGROUND: Dirofilaria repens and D. immitis are filarioid helminths with domestic and wild canids as main hosts and mosquitoes as vectors. Both species are known to cause zoonotic diseases, primarily pulmonary (D. immitis), ocular (D. repens), and subcutaneous (D. repens) dirofilariosis. Both D. immitis and D. repens are known as invasive species, and their distribution seems associated with climate change. Until very recently, both species were known to be nonendemic in Austria. METHODOLOGY AND PRINCIPAL FINDINGS: Metadata on introduced and possibly autochthonous cases of infection with Dirofilaria sp. in dogs and humans in Austria are analysed, together with analyses of mosquito populations from Austria in ongoing studies. In Austria, most cases of Dirofilaria sp. in humans (30 cases of D. repens-six ocular and 24 subcutaneous) and dogs (approximately 50 cases-both D. immitis and D. repens) were most likely imported. However, occasionally infections with D. repens were discussed to be autochthonous (one human case and seven in dogs). The introduction of D. repens to Austria was confirmed very recently, as the parasite was detected in Burgenland (eastern Austria) for the first time in mosquito vectors during a surveillance program. For D. immitis, this could not be confirmed yet, but data from Germany suggest that the successful establishment of this nematode species in Austria is a credible scenario for the near future. CONCLUSIONS: The first findings of D. repens in mosquito vectors indicate that D. repens presumably invaded in eastern Austria. Climate analyses from central Europe indicate that D. immitis also has the capacity to establish itself in the lowland regions of Austria, given that both canid and culicid hosts are present. PMID- 27196050 TI - Cervical Cancer Histology, Staging and Survival before and after Implementation of Organised Cervical Screening Programme in Poland. AB - A population-based organised cervical cancer screening programme (OCCSP) was introduced in Poland in 2006. In this study we have aimed to analyse whether selected parameters related to invasive cervical cancer (ICC) of patients diagnosed in two distant gynaecological oncology centres changed after the first screening round of the programme run between 2006-2008. We have run a retrospective cross-sectional analysis of 189 women diagnosed with ICC between 2002-2005 (directly before introduction of the programme) and 165 patients diagnosed between 2009-2012 (just after the first screening round of the programme) and compared their age at diagnosis, histology, stage of tumours and overall survival (OS). Mean age of patients diagnosed in years 2002-2005 and 2009 2012 was 52.1 and 52.6 years respectively. Squamous cell carcinomas constituted 90.5% and 86.1% of tumours diagnosed in years 2002-2005 and 2009-2012 respectively and the rest of tumours had glandular and other histologies. 74.5% and 61.0% of women diagnosed in years 2002-2005 and 2009-2012 respectively had early ICC (FIGO-International Federation of Gynaecology and Obstetrics stages I IIA) and the rest had advanced disease (FIGO IIB-IV). We have noticed no significant differences in mean age of patients, histology of tumours and OS of patients with ICC diagnosed before and after the first screening round of OCSSP in Poland. Advanced stages of ICC were more commonly diagnosed after the introduction of OCSSP. Changes only in some clinical parameters of patients with ICC were noticed before and after the first screening round of OCSSP in Poland but OS of patients remained the same. PMID- 27196051 TI - Dynamic Measurement of Hemodynamic Parameters and Cardiac Preload in Adults with Dengue: A Prospective Observational Study. AB - Few previous studies have monitored hemodynamic parameters to determine the physiological process of dengue or examined inferior vena cava (IVC) parameters to assess cardiac preload during the clinical phase of dengue. From January 2013 to July 2015, we prospectively studied 162 hospitalized adults with confirmed dengue viral infection using non-invasive cardiac output monitoring and bedside ultrasonography to determine changes in hemodynamic and IVC parameters and identify the types of circulatory shock that occur in patients with dengue. Of 162 patients with dengue, 17 (10.5%) experienced dengue shock and 145 (89.5%) did not. In patients with shock, the mean arterial pressure was significantly lower on day 6 after fever onset (P = 0.045) and the pulse pressure was significantly lower between days 4 and 7 (P<0.05). The stroke volume index and cardiac index were significantly decreased between days 4 and 15 and between days 5 and 8 after fever onset (P<0.05), respectively. A significant proportion of patients with dengue shock had an IVC diameter <1.5 cm and IVC collapsibility index >50% between days 4 and 5 (P<0.05). Hypovolemic shock was observed in 9 (52.9%) patients and cardiogenic shock in 8 (47.1%), with a median (interquartile range) time to shock onset of 6.0 (5.0-6.5) days after fever onset, which was the median day of defervescence. Intravascular hypovolemia occurred before defervescence, whereas myocardial dysfunction occurred on the day of defervescence until 2 weeks after fever onset. Hypovolemic shock and cardiogenic shock each occurred in approximately half of the patients with dengue shock. Therefore, dynamic measures to estimate changes in hemodynamic parameters and preload should be monitored to ensure adequate fluid therapy among patients with dengue, particularly patients with dengue shock. PMID- 27196052 TI - Investigating axial diffusion in cylindrical pores using confocal single-particle fluorescence correlation spectroscopy. AB - We explored the feasibility of using confocal fluorescence correlation spectroscopy to study small nanoparticle diffusion in hundred-nanometer-sized cylindrical pores. By modeling single particle diffusion in tube-like confined three-dimensional space aligned parallel to the confocal optical axis, we showed that two diffusion dynamics can be observed in both original intensity traces and the autocorrelation functions (ACFs): the confined two-dimensional lateral diffusion and the unconfined one-dimensional (1D) axial diffusion. The separation of the axial and confined lateral diffusion dynamics provides an opportunity to study diffusions in different dimensions separately. We further experimentally studied 45 nm carboxylated polystyrene particles diffusing in 300 nm alumina pores. The experimental data showed consistency with the simulation. To extract the accurate axial diffusion coefficient, we found that a 1D diffusion model with a Lorentzian axial collection profile needs to be used to analyze the experimental ACFs. The diffusion of the 45 nm nanoparticles in polyethyleneglycol passivated 300 nm pores slowed down by a factor of ~2, which can be satisfactorily explained by hydrodynamic frictions. PMID- 27196055 TI - Predicting the Direction of Stock Market Index Movement Using an Optimized Artificial Neural Network Model. AB - In the business sector, it has always been a difficult task to predict the exact daily price of the stock market index; hence, there is a great deal of research being conducted regarding the prediction of the direction of stock price index movement. Many factors such as political events, general economic conditions, and traders' expectations may have an influence on the stock market index. There are numerous research studies that use similar indicators to forecast the direction of the stock market index. In this study, we compare two basic types of input variables to predict the direction of the daily stock market index. The main contribution of this study is the ability to predict the direction of the next day's price of the Japanese stock market index by using an optimized artificial neural network (ANN) model. To improve the prediction accuracy of the trend of the stock market index in the future, we optimize the ANN model using genetic algorithms (GA). We demonstrate and verify the predictability of stock price direction by using the hybrid GA-ANN model and then compare the performance with prior studies. Empirical results show that the Type 2 input variables can generate a higher forecast accuracy and that it is possible to enhance the performance of the optimized ANN model by selecting input variables appropriately. PMID- 27196056 TI - Conveying Discovery to a Broad Audience. PMID- 27196053 TI - Increased Cord Blood Betatrophin Levels in the Offspring of Mothers with Gestational Diabetes. AB - AIM: Exposing a fetus to hyperglycemia can increase the risk for later-life metabolic disorders. Betatrophin has been proposed as a key regulator of pancreatic beta cell proliferation and lipid regulation. Highly responsive to nutritional signals, serum betatrophin concentrations have been found to be altered by various physiological and pathological conditions. We hypothesized that betatrophin levels are increased in the cord blood in offspring exposed to intrauterine hyperglycemia. METHODS: This was a cross-sectional study including 54 mothers who underwent uncomplicated Cesarean delivery in a university hospital. Maternal gestational glucose concentration was determined at 24-48 weeks gestation after a 75-g OGTT. Cord blood and placental tissue was collected immediately post delivery. Metabolic parameters were determined in the Clinical Laboratory. Cord blood betatrophin levels were assayed using a commercially available ELISA kit. Placental mitochondrial content was determined by real-time PCR. RESULTS: Cord blood betatrophin levels were increased in the gestational diabetes mellitus (GDM) group compared with the normoglycemic group. Furthermore, betatrophin levels were positively correlated with maternal gestational 2h post OGTT glucose, cord blood insulin, HOMA-IR, and inversely correlated with placental mitochondrial content. CONCLUSIONS: Cord blood betatrophin may function as a potential biomarker of maternal intrauterine hyperglycemia and fetal insulin resistance, which may presage for long-term metabolic impact of GDM on offspring. PMID- 27196054 TI - An Integrated Data Driven Approach to Drug Repositioning Using Gene-Disease Associations. AB - Drug development is both increasing in cost whilst decreasing in productivity. There is a general acceptance that the current paradigm of R&D needs to change. One alternative approach is drug repositioning. With target-based approaches utilised heavily in the field of drug discovery, it becomes increasingly necessary to have a systematic method to rank gene-disease associations. Although methods already exist to collect, integrate and score these associations, they are often not a reliable reflection of expert knowledge. Furthermore, the amount of data available in all areas covered by bioinformatics is increasing dramatically year on year. It thus makes sense to move away from more generalised hypothesis driven approaches to research to one that allows data to generate their own hypothesis. We introduce an integrated, data driven approach to drug repositioning. We first apply a Bayesian statistics approach to rank 309,885 gene disease associations using existing knowledge. Ranked associations are then integrated with other biological data to produce a semantically-rich drug discovery network. Using this network, we show how our approach identifies diseases of the central nervous system (CNS) to be an area of interest. CNS disorders are identified due to the low numbers of such disorders that currently have marketed treatments, in comparison to other therapeutic areas. We then systematically mine our network for semantic subgraphs that allow us to infer drug-disease relations that are not captured in the network. We identify and rank 275,934 drug-disease has_indication associations after filtering those that are more likely to be side effects, whilst commenting on the top ranked associations in more detail. The dataset has been created in Neo4j and is available for download at https://bitbucket.org/ncl-intbio/genediseaserepositioning along with a Java implementation of the searching algorithm. PMID- 27196059 TI - How Bees Deter Elephants: Beehive Trials with Forest Elephants (Loxodonta africana cyclotis) in Gabon. AB - In Gabon, like elsewhere in Africa, crops are often sources of conflict between humans and wildlife. Wildlife damage to crops can drastically reduce income, amplifying poverty and creating a negative perception of wild animal conservation among rural people. In this context, crop-raiding animals like elephants quickly become "problem animals". To deter elephants from raiding crops beehives have been successfully employed in East Africa; however, this method has not yet been tested in Central Africa. We experimentally examined whether the presence of Apis mellifera adansonii, the African honey bee species present in Central Africa, deters forest elephants (Loxodonta Africana cyclotis) from feeding on fruit trees. We show for the first time that the effectiveness of beehives as deterrents of elephants is related to bee activity. Empty hives and those housing colonies of low bee activity do not deter elephants all the time; but beehives with high bee activity do. Although elephant disturbance of hives does not impede honey production, there is a tradeoff between deterrence and the quantity of honey produced. To best achieve the dual goals of deterring elephants and producing honey colonies must maintain an optimum activity level of 40 to 60 bee movements per minute. Thus, beehives colonized by Apis mellifera adansonii bees can be effective elephant deterrents, but people must actively manage hives to maintain bee colonies at the optimum activity level. PMID- 27196057 TI - Surgical Stress Abrogates Pre-Existing Protective T Cell Mediated Anti-Tumor Immunity Leading to Postoperative Cancer Recurrence. AB - Anti-tumor CD8+ T cells are a key determinant for overall survival in patients following surgical resection for solid malignancies. Using a mouse model of cancer vaccination (adenovirus expressing melanoma tumor-associated antigen (TAA) dopachrome tautomerase (AdDCT) and resection resulting in major surgical stress (abdominal nephrectomy), we demonstrate that surgical stress results in a reduction in the number of CD8+ T cell that produce cytokines (IFNgamma, TNFalpha, Granzyme B) in response to TAA. This effect is secondary to both reduced proliferation and impaired T cell function following antigen binding. In a prophylactic model, surgical stress completely abrogates tumor protection conferred by vaccination in the immediate postoperative period. In a clinically relevant surgical resection model, vaccinated mice undergoing a positive margin resection with surgical stress had decreased survival compared to mice with positive margin resection alone. Preoperative immunotherapy with IFNalpha significantly extends survival in surgically stressed mice. Importantly, myeloid derived suppressor cell (MDSC) population numbers and functional impairment of TAA-specific CD8+ T cell were altered in surgically stressed mice. Our observations suggest that cancer progression may result from surgery-induced suppression of tumor-specific CD8+ T cells. Preoperative immunotherapies aimed at targeting the prometastatic effects of cancer surgery will reduce recurrence and improve survival in cancer surgery patients. PMID- 27196060 TI - The VHL short variant involves in protein quality control. AB - The von Hippel-Lindau (VHL) is the most important and frequently mutated gene in human clear cell renal cell carcinoma (ccRCC). In contrast to its long counterpart, the internal translational variant of VHL protein (VHLs) is evolutionarily conserved. Herein we present evidence that VHLs associates with ribosome complex via interaction with the large subunit 6 (RPL6). Manipulation of VHLs expression significantly alters protein synthesis, cell size and mitochondrial mass. VHLs deficiency leads to remarkable sensitivity to drug treatments eliciting nascent protein mis-folding and translational errors. The ubiquitination of nascent peptides are dramatically increased upon the ectopic over-expression of VHLs, which simultaneously co-localizes with proteasome and thus may facilitate the ubiquitin-proteasome mediated degradation. In summary, VHLs contributes to protein quality control in addition to its canonical function in maintaining homeostasis of hypoxia-induced factors alpha subunit (HIFalpha) in response to environmental oxygen supply. PMID- 27196061 TI - Age-related gene expression change of GABAergic system in visual cortex of rhesus macaque. AB - Degradation of visual function is a common phenomenon during aging and likely mediated by change in the impaired central visual pathway. Treatment with GABA or its agonist could recover the ability of visual neurons in the primary visual cortex of senescent macaques. However, little is known about how GABAergic system change is related to the aged degradation of visual function in nonhuman primate. With the use of quantitative PCR method, we measured the expression change of 24 GABA related genes in the primary visual cortex (Brodmann's 17) of different age groups. In this study, both of mRNA and protein of glutamic acid decarboxylase (GAD65) were measured by real-time RT-PCR and Western blot, respectively. Results revealed that the level of GAD65 message was not significantly altered, but the proteins were significantly decreased in the aged monkey. As GAD65 plays an important role in GABA synthesis, the down-regulation of GAD65 protein was likely the key factor leading to the observed GABA reduction in the primary visual cortex of the aged macaques. In addition, 7 of 14 GABA receptor genes were up regulated and one GABA receptor gene was significantly reduced during aging process even after Banjamini correction for multiple comparisons (P<0.05). These results suggested that the dysregulation of GAD65 protein might contribute to some age-related neural visual dysfunctions and most of GABA receptor genes induce a clear indication of compensatory effect for the reduced GABA release in the healthy aged monkey cortex. PMID- 27196058 TI - Hair-Cell Mechanotransduction Persists in TRP Channel Knockout Mice. AB - Members of the TRP superfamily of ion channels mediate mechanosensation in some organisms, and have been suggested as candidates for the mechanotransduction channel in vertebrate hair cells. Some TRP channels can be ruled out based on lack of an inner ear phenotype in knockout animals or pore properties not similar to the hair-cell channel. Such studies have excluded Trpv4, Trpa1, Trpml3, Trpm1, Trpm3, Trpc1, Trpc3, Trpc5, and Trpc6. However, others remain reasonable candidates. We used data from an RNA-seq analysis of gene expression in hair cells as well as data on TRP channel conductance to narrow the candidate group. We then characterized mice lacking functional Trpm2, Pkd2, Pkd2l1, Pkd2l2 and Pkd1l3, using scanning electron microscopy, auditory brainstem response, permeant dye accumulation, and single-cell electrophysiology. In all of these TRP deficient mice, and in double and triple knockouts, mechanotransduction persisted. Together with published studies, these results argue against the participation of any of the 33 mouse TRP channels in hair cell transduction. PMID- 27196062 TI - Chromokinesin: Kinesin superfamily regulating cell division through chromosome and spindle. AB - Material transportation is essential for appropriate cellular morphology and functions, especially during cell division. As a motor protein moving along microtubules, kinesin has several intracellular functions. Many kinesins play important roles in chromosome condensation and separation and spindle organization during the cell cycle. Some of them even can directly bind to chromosomes, as a result, these proteins are called chromokinesins. Kinesin-4 and kinesin-10 family are two major families of chromokinesin and many members can regulate some processes, both in mitosis and meiosis. Their functions have been widely studied. Here, we summarize current knowledge about known chromokinesins and introduce their intracellular features in accordance with different families. Furthermore, we have also introduced some new-found but unconfirmed kinesins which may have a relationship with chromosomes or the cell cycle. PMID- 27196063 TI - Unveiling the interactions among BMPR-2, ALK-1 and 5-HTT genes in the pathophysiology of HAPE. AB - CONTEXT: Few potential candidate genes coding for type I and II receptors of transforming growth factor beta signaling pathway and the serotonin transporter have been associated with pulmonary hypertension (PH). The latter being a phenotype for high altitude pulmonary edema (HAPE), these genes are hypothesized to be crucial markers to investigate under the hypobaric hypoxic environment of high altitude. AIMS: We hence aimed to investigate bone-morphogenetic protein-2 (BMP2), bone morphogenetic protein receptor type-II (BMPR-2), activin receptor like kinase-1 (ALK-1), serotonin transporter (5-HTT) and serotonin (5-HT) for their contribution, individually/epistatically, to clinical endpoints by altering downstream signaling molecules. METHODS AND MATERIALS: In a case-control design, interactions between/among polymorphisms of BMPR-2, ALK-1 and 5-HTT were screened in 200 HAPE-patients (HAPE-p) and 200 HAPE-free sojourners (HAPE-f). Plasma biomarker BMP-2 and 5-HT were estimated. The relative gene expression was also witnessed in 20 humans/10 rats followed by correlation analyses. RESULTS: The genotype/allele models revealed the prevalence of BMPR-2 rs6717924A-rs4303700A rs1048829A; ALK-1 rs11169953T-rs3759178C-rs706816C and 5-HTT rs6354C in HAPE (P<=0.05). Multifactor dimensionality reduction for interactions among genes revealed a 4-locus model of BMPR-2 rs6717924G/A; ALK-1 rs11169953C/T-rs706816T/C and 5-HTT rs6354A/C as the best disease predicting (P<=0.001); whereas HapEvolution analysis confirmed the alleles rs6717924A, rs4303700A and rs6354C as the best interacting (P<=0.01). Plasma levels of BMP-2 and 5-HT were elevated in HAPE (P<=0.0001). The expression of BMP-2, ALK-1, 5-HT, 5-HTT was elevated and of BMPR-2 decreased in humans and rats (P<=0.05). The risk alleles BMPR-2 rs6717924A rs4303700G-rs1048829A; ALK-1 rs11169953T-rs706816C and 5-HTT rs6354C correlated inversely with arterial oxygen saturation (SaO2) and positively with mean arterial pressure (MAP), BMP-2 and 5-HT in HAPE. Likewise, haplotypes BMPR-2 GGGCGAAAA, AAATAGGGA and ALK-1 CCTCAAAG, CCTTAAAG correlated with clinical markers and biomarkers (P<=0.01). BMP-2 and 5-HT correlated positively with MAP and negatively with SaO2 (P<=0.01). CONCLUSIONS: The genetic-interactions among BMPR-2, ALK-1, and 5-HTT polymorphisms, elevated BMP-2 and 5-HT levels and differential gene expression substantiated the strong genetic contribution in HAPE pathophysiology. PMID- 27196064 TI - The Metabolism of Clopidogrel: CYP2C19 Is a Minor Pathway. AB - The major metabolic pathway of clopidogrel is conversion to carboxylic acid by an esterase (CES1), forming clopidogrelic acid (SR26334) that is inactive. There is agreement on the structure of the active metabolite; however, there are differing views about the mechanism of its formation. Sanofi studied the conversion of clopidogrel to the active metabolite using human liver microsomes. It was concluded that 2-oxo-clopidogrel was formed via CYP3A oxidation. From a subsequent in vitro study by Sankyo of the metabolism of clopidogrel using recombinant DNA CYPs, it was concluded that CYP2C19 was the major oxidative pathway. Such CYPs can give false-negative results particularly with drugs such as clopidogrel that have high first-pass metabolism in the enterocyte. CYP3A is present in the enterocyte but not CYP2C19. However, the view that clopidogrel is a CYP2C19 substrate was reinforced by a finding that omeprazole, a CYP2C19 inhibitor, reduced the ability of clopidogrel to inhibit platelet aggregation. The drug-drug interaction study of clopidogrel with omeprazole had the effect of reducing the area under the curve (AUC) of the clopidogrel active metabolite by 45%. However, a drug interaction study with a CYP3A inhibitor, grapefruit juice, caused a 6-fold reduction in the AUC of the active metabolite. Clopidogrel is therefore now considered to be primarily a CYP3A4/5 substrate. CYP2C19 has a minor role whose effect can be detected using a sensitive methodology such as platelet aggregometry. PMID- 27196065 TI - Metagenomic Analysis of the Indian Ocean Picocyanobacterial Community: Structure, Potential Function and Evolution. AB - Unicellular cyanobacteria are ubiquitous photoautotrophic microbes that contribute substantially to global primary production. Picocyanobacteria such as Synechococcus and Prochlorococcus depend on chlorophyll a-binding protein complexes to capture light energy. In addition, Synechococcus has accessory pigments organized into phycobilisomes, and Prochlorococcus contains chlorophyll b. Across a surface water transect spanning the sparsely studied tropical Indian Ocean, we examined Synechococcus and Prochlorococcus occurrence, taxonomy and habitat preference in an evolutionary context. Shotgun sequencing of size fractionated microbial communities from 0.1 MUm to 20 MUm and subsequent phylogenetic analysis indicated that cyanobacteria account for up to 15% of annotated reads, with the genera Prochlorococcus and Synechococcus comprising 90% of the cyanobacterial reads, even in the largest size fraction (3.0-20 mm). Phylogenetic analyses of cyanobacterial light-harvesting genes (chl-binding pcb/isiA, allophycocyanin (apcAB), phycocyanin (cpcAB) and phycoerythin (cpeAB)) mostly identified picocyanobacteria clades comprised of overlapping sequences obtained from Indian Ocean, Atlantic and/or Pacific Oceans samples. Habitat reconstructions coupled with phylogenetic analysis of the Indian Ocean samples suggested that large Synechococcus-like ancestors in coastal waters expanded their ecological niche towards open oligotrophic waters in the Indian Ocean through lineage diversification and associated streamlining of genomes (e.g. loss of phycobilisomes and acquisition of Chl b); resulting in contemporary small celled Prochlorococcus. Comparative metagenomic analysis with picocyanobacteria populations in other oceans suggests that this evolutionary scenario may be globally important. PMID- 27196066 TI - Expression of Quaking RNA-Binding Protein in the Adult and Developing Mouse Retina. AB - Quaking (QKI), which belongs to the STAR family of KH domain-containing RNA binding proteins, functions in pre-mRNA splicing, microRNA regulation, and formation of circular RNA. QKI plays critical roles in myelinogenesis in the central and peripheral nervous systems and has been implicated neuron-glia fate decision in the brain; however, neither the expression nor function of QKI in the neural retina is known. Here we report the expression of QKI RNA-binding protein in the developing and mature mouse retina. QKI was strongly expressed by Muller glial cells in both the developing and adult retina. Intriguingly, during development, QKI was expressed in early differentiating neurons, such as the horizontal and amacrine cells, and subsequently in later differentiating bipolar cells, but not in photoreceptors. Neuronal expression was uniformly weak in the adult. Among QKI isoforms (5, 6, and 7), QKI-5 was the predominantly expressed isoform in the adult retina. To study the function of QKI in the mouse retina, we examined quakingviable(qkv) mice, which have a dysmyelination phenotype that results from deficiency of QKI expression and reduced numbers of mature oligodendrocytes. In homozygous qkv mutant mice (qkv/qkv), the optic nerve expression levels of QKI-6 and 7, but not QKI-5 were reduced. In the retina of the mutant homozygote, QKI-5 levels were unchanged, and QKI-6 and 7 levels, already low, were also unaffected. We conclude that QKI is expressed in developing and adult Muller glia. QKI is additionally expressed in progenitors and in differentiating neurons during retinal development, but expression weakened or diminished during maturation. Among QKI isoforms, we found that QKI-5 predominated in the adult mouse retina. Since Muller glial cells are thought to share properties with retinal progenitor cells, our data suggest that QKI may contribute to maintaining retinal progenitors prior to differentiation into neurons. On the other hand, the expression of QKI in different retinal neurons may suggest a role in neuronal cell type specific fate determination and maturation. The data raises the possibility that QKI may function in retinal cell fate determination and maturation in both glia and neurons. PMID- 27196069 TI - A note from the editors: enterovirus D68 epidemiology in France and Germany-food for thought. PMID- 27196067 TI - Differential Contributions of Intrinsic and Extrinsic Pathways to Thrombin Generation in Adult, Maternal and Cord Plasma Samples. AB - BACKGROUND: Thrombin generation (TG) is a pivotal process in achieving hemostasis. Coagulation profiles during pregnancy and early neonatal period are different from that of normal (non-pregnant) adults. In this ex vivo study, the differences in TG in maternal and cord plasma relative to normal adult plasma were studied. METHODS: Twenty consented pregnant women and ten consented healthy adults were included in the study. Maternal and cord blood samples were collected at the time of delivery. Platelet-poor plasma was isolated for the measurement of TG. In some samples, anti-FIXa aptamer, RB006, or a TFPI inhibitor, BAX499 were added to elucidate the contribution of intrinsic and extrinsic pathway to TG. Additionally, procoagulant and inhibitor levels were measured in maternal and cord plasma, and these values were used to mathematically simulate TG. RESULTS: Peak TG was increased in maternal plasma (393.6+/-57.9 nM) compared to adult and cord samples (323.2+/-38.9 nM and 209.9+/-29.5 nM, respectively). Inhibitory effects of RB006 on TG were less robust in maternal or cord plasma (52% vs. 12% respectively) than in adult plasma (81%). Likewise the effectiveness of BAX499 as represented by the increase in peak TG was much greater in adult (21%) than in maternal (10%) or cord plasma (12%). Further, BAX499 was more effective in reversing RB006 in adult plasma than in maternal or cord plasma. Ex vivo data were reproducible with the results of the mathematical simulation of TG. CONCLUSION: Normal parturient plasma shows a large intrinsic pathway reserve for TG compared to adult and cord plasma, while TG in cord plasma is sustained by extrinsic pathway, and low levels of TFPI and AT. PMID- 27196068 TI - ABCG1 and ABCG4 Suppress gamma-Secretase Activity and Amyloid beta Production. AB - ATP-binding cassette G1 (ABCG1) and ABCG4, expressed in neurons and glia in the central nervous system, mediate cholesterol efflux to lipid acceptors. The relationship between cholesterol level in the central nervous system and Alzheimer's disease has been reported. In this study, we examined the effects of ABCG1 and ABCG4 on amyloid precursor protein (APP) processing, the product of which, amyloid beta (Abeta), is involved in the pathogenesis of Alzheimer's disease. Expression of ABCG1 or ABCG4 in human embryonic kidney 293 cells that stably expressed Swedish-type mutant APP increased cellular and cell surface APP levels. Products of cleavage from APP by alpha-secretase and by beta-secretase also increased. The levels of secreted Abeta, however, decreased in the presence of ABCG1 and ABCG4, but not ABCG4-KM, a nonfunctional Walker-A lysine mutant. In contrast, secreted Abeta levels increased in differentiated SH-SY5Y neuron-like cells in which ABCG1 and ABCG4 were suppressed. Furthermore, Abeta42 peptide in the cerebrospinal fluid from Abcg1 null mice significantly increased compared to the wild type mice. To examine the underlying mechanism, we analyzed the activity and distribution of gamma-secretase. ABCG1 and ABCG4 suppressed gamma-secretase activity and disturbed gamma-secretase localization in the raft domains where gamma-secretase functions. These results suggest that ABCG1 and ABCG4 alter the distribution of gamma-secretase on the plasma membrane, leading to the decreased gamma-secretase activity and suppressed Abeta secretion. ABCG1 and ABCG4 may inhibit the development of Alzheimer's disease and can be targets for the treatment of Alzheimer's disease. PMID- 27196070 TI - Aspects of cerebral plasticity related to clinical features in acute vestibular neuritis: a "starting point" review from neuroimaging studies. AB - Vestibular neuritis (VN) is one of the most common causes of vertigo and is characterised by a sudden unilateral vestibular failure (UVF). Many neuroimaging studies in the last 10 years have focused on brain changes related to sudden vestibular deafferentation as in VN. However, most of these studies, also due to different possibilities across diverse centres, were based on different times of first acquisition from the onset of VN symptoms, neuroimaging techniques, statistical analysis and correlation with otoneurological and psychological findings. In the present review, the authors aim to merge together the similarities and discrepancies across various investigations that have employed neuroimaging techniques and group analysis with the purpose of better understanding about how the brain changes and what characteristic clinical features may relate to each other in the acute phase of VN. Six studies that strictly met inclusion criteria were analysed to assess cortical-subcortical correlates of acute clinical features related to VN. The present review clearly reveals that sudden UVF may induce a wide variety of cortical and subcortical responses - with changes in different sensory modules - as a result of acute plasticity in the central nervous system. PMID- 27196071 TI - Intraoperative radiation therapy as adjuvant treatment in locally advanced stage tumours involving the middle ear: a hypothesis-generating retrospective study. AB - The objective of this study was to evaluate the safety, effectiveness and functional outcomes of intraoperative radiotherapy (IORT) followed by intensity modulated radiation therapy (IMRT) in locally advanced stage tumours involving the middle ear. Data on 13 consecutive patients treated for malignant tumor of external auditory canal involving the middle ear were retrospectively reviewed. Median follow-up was 33 months (range 6-133). Five (38%) patients were stage III and 8 (62%) were Stage IV according to the University of Pittsburgh staging system. Lateral temporal bone resection (LTBR) was performed in all cases. LTBR was associated with parotidectomy in 5 (38%) cases, and with neck dissection and parotidectomy in 6 (46%) cases. No patients had gross residual tumour. Surgical treatment was followed by IORT (12 Gy) and IMRT (50 Gy). Adjuvant chemotherapy was used in 4 (30%) cases. Preoperative and postoperative audiometric tests were performed to assess hearing loss. 5-year local-control (LC), 5-year distant metastasis (DM), 5-year disease-free-survival (DFS) and 5-year overall-survival (OS) were calculated with Kaplan-Meyer method. Significant changes in bone conduction were reported after treatment. Partial flap necrosis was the only early complication observed in three (23%) cases, while meningeal fistula was seen in one (7.6%) case as a late complication. The 5-year LC-rate was 68%. The 5 year DM-rate was 90%. The 5-year DFS-rate was 61%. The 5-year OS-rate was 69%. IORT followed by IMRT for the treatment of advanced external auditory canal and middle ear tumours seems to be safe. No intraoperative death was reported. IORT may reduce the postoperative irradiation of remnant tissue obtaining the same full dose on the tumour bed. No complications of the residual external ear were observed. Detriment of neurosensory hearing may be expected. Future studies are required to confirm the benefit of this procedure in the ear. PMID- 27196073 TI - The effects of inferior turbinoplasty on nasal airflow during cosmetic rhinoplasty. AB - Rhinoplasty is one of the most common and challenging cosmetic procedures. One of the complications of rhinoplasty associated with dissatisfaction is nasal obstruction, which is often due to narrowing of the nasal valve area. Application of certain procedures such as turbinoplasty can prevent and correct this problem. This study aim was to investigate the effect of inferior turbinoplasty in reduction of airflow resistance and nasal obstruction. Using active anterior rhinomanometry, nasal airflow was measured in 50 patients who underwent cosmetic rhinoplasty and bilateral turbinoplasty before and 6 months after surgery. None of the patients subjectively complained of nasal obstruction before or after surgery. According to rhinomanometry results, improvement in nasal airflow was seen both in inspiration and expiration, although only expiration was significant (p = 0.034). Airflow changes in males and females and in different age groups was not significant (p > 0.05). It appears that rhinoplasty does not adversely affect nasal airflow when it is accompanied by simple adjuvant procedure inferior turbinoplasty. PMID- 27196072 TI - Post-operative pain management in head and neck cancer patients: predictive factors and efficacy of therapy. AB - There is increasing interest about all aspects of pain sensation for patients undergoing head and neck surgery, and efforts have been made to better assess, monitor and reduce the occurrence of pain. The aetiology of pain is considered to be "multifactorial", as it is defined by several features such as personal experience, quality perception, location, intensity and emotional impact. The aim of this paper is: (i) to evaluate the efficacy of analgesic treatment in patients with head and neck cancer treated by surgery, and (ii) to study the variables and predictive factors that can influence the occurrence of pain. A total of 164 patients, affected by head and neck cancer and surgically treated, between December 2009 and December 2013, were included in this study. Data collected include age, gender, assessment of anaesthetic risk, tumour localisation, pathological cancer stage, TNM stage, type of surgery performed, complexity and duration of surgery, post-operative complications, postoperative days of hospital stay and pain evaluation on days 0, 1, 3 and 5 post-surgery. We studied the appropriateness of analgesic therapy in terms of incidence and prevalence of post operative pain; we also related pain to patient characteristics, disease and surgical treatment to determine possible predictive factors. The population studied received adequate pain control through analgesic therapy immediately post surgery and in the following days. No associations between gender, age and post operative pain were found, whereas pathological cancer stage, complexity of surgery and tumour site were significantly associated with the risk of post operative pain. Adequate pain control is essential in oncological patients, and particularly in head and neck cancer patients as the prevalence of pain in this localisation is reported to be higher than in other anatomical sites. Improved comprehension of the biological and psychological factors that characterise pain perception will help to enhance its control in the future. PMID- 27196074 TI - In vivo tissue response and durability of five novel synthetic polymers in a rabbit model. AB - Alloplastic materials are frequently used in facial plastic surgeries such as rhinoplasty and nasal reconstruction. Unfortunately, the ideal alloplastic material has not been found. This experimental study evaluates the tissue response and durability of five novel polymers developed as an alloplastic material. In this experimental study involving a tertiary university hospital, six subcuticular pockets were formed at the back of 10 rabbits for the implantation of each polymer and sham group. Each pocket was excised with its adjacent tissue after three months, and collected for histopathological examination. Semi-quantitative examination including neovascularisation, inflammation, fibrosis, abscess formation, multinucleated foreign body giant cells was performed, and integrity of polymer was evaluated. A statistical comparison was performed. No statically significant difference was detected in neovascularisation, inflammation, fibrosis, abscess formation and multinucleated foreign body giant cells when a paired comparison between sham and polymer II, III and IV groups was performed individually. Nevertheless, the degree of fibrosis was less than sham group in polymer I (p = .027) and V (p = .018), although the other variables were almost similar. The integrity of polymers III (9 intact, 1 fragmented) and IV (8 intact, 2 absent) was better than the other polymers. These novel synthetic polymers could be considered as good candidates for clinical applicability. All polymers provided satisfactory results in terms of tissue response; however, fibrovascular integration was higher in polymers II, III and IV. In addition, the durability of polymer III and IV was better than the others. PMID- 27196075 TI - Endoscopic endonasal approach to the craniocervical junction: the importance of anterior C1 arch preservation or its reconstruction. AB - We report our experience with the endoscopic endonasal approaches (EEA) for different craniocervical junction (CCJ) disorders to analyse outcomes and demonstrate the importance and feasibility of anterior C1 arch preservation or its reconstruction. Between January 2009 and December 2013, 10 patients underwent an endoscopic endonasal approach for different CCJ pathologies at our Institution. In 8 patients we were able to preserve the anterior C1 arch, while in 2 post-traumatic cases we reconstructed it. The CCJ disorders included 4 cases of irreducible anterior bulbo-medullary compression secondary to rheumatoid arthritis or CCJ anomalies, 4 cases of inveterate fractures of C1 and/or C2 and 2 tumours. Pre- and postoperative neuroradiological evaluation was always obtained by magnetic resonance imaging (MRI), computed tomographic (CT) scanning and dynamic cranio-vertebral junction x-ray. Pre- and postoperative neurologic disability assessment was obtained by Ranawat classification for patients with rheumatoid arthritis and by Nurick classification for the others. At a mean follow-up of 31 months (range: 14-73 months), an improvement of at least one Ranawat or Nurick classification level was observed in 6 patients, while in another 4 patients neurological conditions were stable. Radiological follow-up revealed an adequate bulbo-medullary decompression in all patients and a regular bone fusion in cases of C1 and/or C2 fractures. In all patients spinal stability was preserved and none required subsequent posterior fixation. The endoscopic endonasal surgery provided adequate exposure and a low morbidity minimally invasive approach to the antero-medial located lesions of the CCJ, resulting in a safe, effective and well-tolerated procedure. This approach allowed preservation of the anterior C1 arch and the avoidance of a posterior fixation in all patients of this series, thus preserving the rotational movement at C0-C2 segment and reducing the risk of a subaxial instability development. PMID- 27196076 TI - Idiopathic sensorineural hearing loss in the only hearing ear. AB - A retrospective chart review was used for 31 patients with sudden, progressive or fluctuating sensorineural hearing loss (SHL) in the only hearing ear who had been consecutively evaluated at the ENT, Audiology and Phoniatrics Unit of the University of Pisa. The group of patients was evaluated with a complete history review, clinical evaluation, imaging exam (MRI, CT), audiologic tests (tone and speech audiometry, tympanometry, study of stapedial reflexes, ABR and otoacoustic emission) evaluation. In order to exclude genetic causes, patients were screened for CX 26 and CX30 mutations and for mitochondrial DNA mutation A1555G. Patients with sudden or rapidly progressive SHL in the only hearing ear were treated with osmotic diuretics and corticosteroids. In patients who did not respond to intravenous therapy we performed intratympanic injections of corticosteroid. Hearing aids were fitted when indicated and patients who developed severe to profound SHL were scheduled for cochlear implant surgery. The aim of this study is to report and discuss the epidemiology, aetiopathogenesis, therapy and clinical characteristic of patients affected by SHL in the only hearing hear and to discuss the issues related to the cochlear implant procedure in some of these patients, with regard to indications, choice of the ear to implant and results. PMID- 27196077 TI - Early and late surgical site infections in ear surgery. AB - A retroauricular approach is routinely used for treating chronic otitis media. The incidence of surgical site infections after ear surgery is around 10% in contaminated or dirty procedures. This observational prospective study describes surgical site infections after chronic otitis media surgery with the retroauricular approach and investigated their potential predictive factors. This observational prospective study included patients suffering from chronic otitis media and eligible for therapeutic surgery with a retroauricular approach. During follow-up, surgical site infections were defined as "early" if occurring within 30 days after surgery or as "late" if occurring thereafter. The data of 102 patients were analysed. Concerning early surgical site infections, four cases were diagnosed (3.9%) and a significant association was found with preoperative antibiotic therapy, wet ear at pre-operative examination, class III (contaminated) in the surgical wound classification, NNIS (National Nosocomial Infection Surveillance) index > 1, and oral post-operative antibiotic use. Seven late surgical site infections were diagnosed (7.1%) between 90 and 160 days after surgery and were significantly correlated to otorrhoea during the 6 months before surgery, surgery duration <=60 minutes, canal wall down technique and use of fibrin glue. Surgical site infections after chronic otitis media surgery seem to be associated with factors related to the inflammatory state of the middle ear at the time of surgery in early infections and with chronic inflammation in late infections. PMID- 27196078 TI - Can the learning curve in stapes surgery predict future functional outcome? AB - Over the last 20 years, the number of stapes operations performed has decreased steadily. This inadequate exposure to stapes surgery poses problems for both trainees and trainers. We retrospectively reviewed the outcomes of stapedotomy performed by a young physician at the ENT Clinic of the "A. Gemelli" Hospital of Rome. We used the technique of "one-shot" CO2 Laser stapedotomy using a titanium Teflon piston. For data analysis, we considered the audiograms obtained 24 hours preoperatively and at the last follow-up examination (mean 45 months). Air conduction (AC) and bone conduction (BC) PTA were calculated for 0.25, 0.5, 1, 2 and 4 kHz thresholds. Air bone gap (ABG) were obtained from ACPTA and BCPTA. Postoperative hearing gain was calculated from the ABG before the operation minus the ABG at late follow-up examination. Analysis of outcomes did not show a clear endpoint for the learning curve; complete closure of the ABG was obtained in a large number of patients at the beginning followed by patients who showed a higher ABG. Fortunately, we did not observed any "dead ear". The study supports a learning curve in stapes surgery, but the results can vary widely among surgeries with excellent results followed by others that are not fully satisfactory. Stapes surgery should not be one of the first ear surgeries performed by a young otologist due to the functional outcome expected by patients and the lack of necessary surgical skills. PMID- 27196079 TI - Oral cavity reconstruction with the masseter flap. AB - The purpose of this report is to highlight how an unusual, outdated, unpopular and overlooked reconstructive method such as the masseter flap can be a reliable, straightforward and effective solution for oral reconstruction in selected cases. We report the transposition of the masseter crossover flap in two previously pre treated patients presenting a second primary oral squamous cell carcinoma; excellent functional results with satisfactory cosmetic appearance were obtained in both cases. In the literature, only 60 cases of oral cavity and oropharyngeal reconstructions using the masseter flap have been reported. The possible clinical utility of this flap, even in modern head and neck reconstructive surgery, is presented and discussed. We believe that the masseter flap should enter in the armamentarium of every head and neck surgeon and be kept in mind as a possible solution since it provides an elegant and extremely simple procedure in suboptimal cases for microvascular reconstruction. PMID- 27196080 TI - Endonasal endoscopic resection of ossifying fibroma involving the ethmoid sinus, orbit and anterior skull base: case report and literature review. AB - Ossifying fibroma is a benign fibro-osseous tumour that rarely involves the ethmoid sinuses and orbit. It is classified as a benign fibroosseous lesion, a term that is synonymous with a variety of lesions reported in the literature. Recurrence rate with deleterious effects in cases of extramandibular ossifying fibroma is the impetus for open en bloc resection of the tumour. Continuously evolving techniques in endonasal endoscopic sinus surgery has rendered resection of large benign sinonasal and cephalonasal tumours possible. The authors report a case of ossifying fibroma involving the ethmoid sinus, orbit and anterior skull base in a 65-year-old previously healthy woman completely resected by endonasal endoscopic sinus surgery. The patient was free from postoperative complications and was dismissed from hospital on the sixth postoperative day. At present, the patient is disease-free at a regular five-year postoperative follow-up. Endonasal endoscopic resection of sinonasal ossifying fibromas is an excellent therapeutic option when performed by a surgeon experienced in endoscopic sinonasal surgery. The advantages of an endonasal endoscopic approach include direct visualization, enhanced visibility and magnification resulting in decreased intraoperative and postoperative morbidity. Aesthetic outcome is excellent in the absence of facial scars. PMID- 27196081 TI - Traumatic intra-sphenoidal pseudoaneurysm lodged inside the fractured sphenoidal sinus. AB - We describe a case of traumatic intra-sphenoidal right internal carotid artery pseudoaneurysm lodged inside the fractured sphenoidal sinus that developed in a patient with a previous history of frontal and skull base fractures involving the sphenoid sinus and walls of the carotid canal, but with normal intracranial findings at early CT angiography. The patient presented two episodes of massive life-threatening delayed epistaxis before successful endovascular treatment combining the use of coils and an uncovered stent was instituted. This case report highlights that patients with head trauma who present sphenoid sinus fractures with or without massive epistaxis should be evaluated for the development of traumatic internal carotid artery pseudoaneurysm as soon as possible. If the first angiographic evaluation reveals normal findings, repeated epistaxis should prompt a second angiographic evaluation because psudoaneurysm takes time to develop. Early treatment with uncovered stent of the aneurysm can be a life-saving therapeutic approach. PMID- 27196082 TI - Associations Between Parkinson Disease and Cancer in US Asian Americans. PMID- 27196084 TI - Repeated sustained release dinoprostone vaginal inserts in women with unfavorable cervix may increase the risk of postpartum hemorrhage: preliminary results. PMID- 27196083 TI - Validation of Novel Biomarkers for Prostate Cancer Progression by the Combination of Bioinformatics, Clinical and Functional Studies. AB - The identification and validation of biomarkers for clinical applications remains an important issue for improving diagnostics and therapy in many diseases, including prostate cancer. Gene expression profiles are routinely applied to identify diagnostic and predictive biomarkers or novel targets for cancer. However, only few predictive markers identified in silico have also been validated for clinical, functional or mechanistic relevance in disease progression. In this study, we have used a broad, bioinformatics-based approach to identify such biomarkers across a spectrum of progression stages, including normal and tumor-adjacent, premalignant, primary and late stage lesions. Bioinformatics data mining combined with clinical validation of biomarkers by sensitive, quantitative reverse-transcription PCR (qRT-PCR), followed by functional evaluation of candidate genes in disease-relevant processes, such as cancer cell proliferation, motility and invasion. From 300 initial candidates, eight genes were selected for validation by several layers of data mining and filtering. For clinical validation, differential mRNA expression of selected genes was measured by qRT-PCR in 197 clinical prostate tissue samples including normal prostate, compared against histologically benign and cancerous tissues. Based on the qRT-PCR results, significantly different mRNA expression was confirmed in normal prostate versus malignant PCa samples (for all eight genes), but also in cancer-adjacent tissues, even in the absence of detectable cancer cells, thus pointing to the possibility of pronounced field effects in prostate lesions. For the validation of the functional properties of these genes, and to demonstrate their putative relevance for disease-relevant processes, siRNA knock down studies were performed in both 2D and 3D organotypic cell culture models. Silencing of three genes (DLX1, PLA2G7 and RHOU) in the prostate cancer cell lines PC3 and VCaP by siRNA resulted in marked growth arrest and cytotoxicity, particularly in 3D organotypic cell culture conditions. In addition, silencing of PLA2G7, RHOU, ACSM1, LAMB1 and CACNA1D also resulted in reduced tumor cell invasion in PC3 organoid cultures. For PLA2G7 and RHOU, the effects of siRNA silencing on proliferation and cell-motility could also be confirmed in 2D monolayer cultures. In conclusion, DLX1 and RHOU showed the strongest potential as useful clinical biomarkers for PCa diagnosis, further validated by their functional roles in PCa progression. These candidates may be useful for more reliable identification of relapses or therapy failures prior to the recurrence local or distant metastases. PMID- 27196085 TI - Hysterectomy for benign disease: clinical practice guidelines from the French College of Obstetrics and Gynecology. AB - OBJECTIVE: The objective of the study was to draw up French College of Obstetrics and Gynecology (CNGOF) clinical practice guidelines based on the best available evidence concerning hysterectomy for benign disease. METHODS: Each recommendation for practice was allocated a grade, which depends on the level of evidence (clinical practice guidelines). RESULTS: Hysterectomy should be performed by a high-volume surgeon (>10 hysterectomy procedures per year) (gradeC). Stimulant laxatives taken as a rectal enema are not recommended prior to hysterectomy (gradeC). It is recommended to carry out vaginal disinfection using povidone iodine solution prior to hysterectomy (grade B). Antibiotic prophylaxis is recommended during hysterectomy, regardless of the surgical approach (grade B). The vaginal or laparoscopic approach is recommended for hysterectomy for benign disease (grade B), even if the uterus is large and/or the patient is obese (gradeC). The choice between these two surgical approaches depends on other parameters, such as the surgeon's experience, the mode of anesthesia, and organizational constraints (duration of surgery and medical economic factors). Vaginal hysterectomy is not contraindicated in nulliparous women (gradeC) or in women with previous cesarean section (gradeC). No specific hemostatic technique is recommended with a view to avoiding urinary tract injury (gradeC). In the absence of ovarian disease and a personal or family history of breast/ovarian carcinoma, the ovaries should be preserved in pre-menopausal women (grade B). Subtotal hysterectomy is not recommended with a view to reducing the risk of peri or postoperative complications (grade B). CONCLUSION: The application of these recommendations should minimize risks associated with hysterectomy. PMID- 27196088 TI - Defining Priorities for Reducing Disparities in Cancer Mortality. PMID- 27196090 TI - The New Vital Sign: Where Do You Live? PMID- 27196086 TI - Comparison of Antibodies with Amylase Activity from Cerebrospinal Fluid and Serum of Patients with Multiple Sclerosis. AB - We have recently shown that IgGs from serum and cerebrospinal fluid (CSF) of MS patients are active in hydrolysis of DNA and myelin basic protein. According to literature data, anti-DNA and anti-MBP abzymes may promote important neuropathologic mechanisms in this chronic inflammatory disorder and in MS pathogenesis development. At the same time, the involvement of antibodies with amylase activity in the pathogenesis of any autoimmune disease has not yet been identified. Electrophoretically and immunologically homogeneous IgGs were obtained by a sequential affinity chromatography of the CSF proteins on protein G Sepharose and FPLC gel filtration. We are able to present the first unpredictable evidence showing that IgGs from CSF possess amylase activity and efficiently hydrolyze maltoheptaose; their average specific Ab activity is ~30-fold higher than that of antibodies from sera of the same MS patients. Specific average RA (SAA) for IgGs from healthy volunteers was approximately ~1000 lower than that for MS patients. In addition, it was shown that a relative SAA of total proteins of CSF (including Abs) ~15-fold lower than that for purified IgGs, while the relative SAA of the total sera protein is higher than that of sera IgGs by a factor of 1033. This result speaks in favor of the fact that amylolytic activity of CSF proteins is mainly caused by the activity of amylase abzymes. One cannot exclude, that amylase abzymes of CSF can play a, as yet unknown, role in the pathogenesis of MS. Some possible reasons of these findings are discussed. PMID- 27196091 TI - Informing Future Population Health Interventions. PMID- 27196092 TI - Multilevel Intervention Raises Latina Participation in Mammography Screening: Findings from !Fortaleza Latina! AB - BACKGROUND: Breast cancer is the most commonly diagnosed cancer in women in the United States, and Latinas have relatively low rates of screening participation. The Multilevel Intervention to Increase Latina Participation in Mammography Screening study (!Fortaleza Latina!) sought to assess the efficacy of a clinic- and patient-level program to increase breast cancer screening among Latinas in Western Washington who seek care at a safety net health center. METHODS: The study enrolled 536 Latinas ages 42 to 74 who had a primary care clinic visit in the previous 5 years and had not obtained a mammogram in the previous 2 years. Participants were block-randomized within clinic to either (i) a control arm (usual care) or (ii) a promotora-led, motivational interviewing intervention that included a home visit and telephone follow-up. At the clinic level, two of four participating clinics were provided additional mammography services delivered by a mobile mammography unit. RESULTS: Rates of screening mammography 1 year post randomization were 19.6% in the intervention group and 11.0% in the usual care group (P < 0.01), based on medical record data. No significant differences in participants' mammography screening were observed in clinics randomized to additional mammography services versus usual care (15.8% vs. 14.4%; P = 0.68). CONCLUSION: This multilevel intervention of promotora-delivered motivational interviewing and free mammography services modestly raised rates of participation in breast cancer screening among Latinas. IMPACT: Our findings can inform future efforts to boost mammography participation in safety net practices. Cancer Epidemiol Biomarkers Prev; 25(4); 584-92. (c)2016 AACR SEE ALL ARTICLES IN THIS CEBP FOCUS SECTION, "MULTILEVEL APPROACHES TO ADDRESSING CANCER HEALTH DISPARITIES". PMID- 27196089 TI - Recommendations for Cancer Epidemiologic Research in Understudied Populations and Implications for Future Needs. AB - Medically underserved populations in the United States continue to experience higher cancer burdens of incidence, mortality, and other cancer-related outcomes. It is imperative to understand how health inequities experienced by diverse population groups may contribute to our increasing unequal cancer burdens and disparate outcomes. The National Cancer Institute convened a diverse group of scientists to discuss research challenges and opportunities for cancer epidemiology in medically underserved and understudied populations. This report summarizes salient issues and discusses five recommendations from the group, including the next steps required to better examine and address cancer burden in the United States among our rapidly increasing diverse and understudied populations. Cancer Epidemiol Biomarkers Prev; 25(4); 573-80. (c)2016 AACR SEE ALL ARTICLES IN THIS CEBP FOCUS SECTION, "MULTILEVEL APPROACHES TO ADDRESSING CANCER HEALTH DISPARITIES". PMID- 27196094 TI - Prevalence and Framing of Health Disparities in Local Print News: Implications for Multilevel Interventions to Address Cancer Inequalities. AB - BACKGROUND: Americans remain under-informed about cancer and other health disparities and the social determinants of health (SDH). The news media may be contributing to this knowledge deficit, whether by discussing these issues narrowly or ignoring them altogether. Because local media are particularly important in influencing public opinion and support for public policies, this study examines the prevalence and framing of disparities/SDH in local mainstream and ethnic print news. METHODS: We conducted a multi-method content analysis of local mainstream (English language) and ethnic (Spanish language) print news in two lower income cities in New England with substantial racial/ethnic minority populations. After establishing intercoder reliability (kappa = 0.63-0.88), coders reviewed the primary English and Spanish language newspaper in each city, identifying both disparities and non-disparities health stories published between February 2010 and January 2011. RESULTS: Local print news coverage of cancer and other health disparities was rare. Of 650 health stories published across four newspapers during the one-year study period, only 21 (3.2%) discussed disparities/SDH. Although some stories identified causes of and solutions for disparities, these were often framed in individual (e.g., poor dietary habits) rather than social contextual terms (e.g., lack of food availability/affordability). Cancer and other health stories routinely missed opportunities to discuss disparities/SDH. CONCLUSION: Local mainstream and ethnic media may be ideal targets for multilevel interventions designed to address cancer and other health inequalities. IMPACT: By increasing media attention to and framing of health disparities, we may observe important downstream effects on public opinion and support for structural solutions to disparities, particularly at the local level. Cancer Epidemiol Biomarkers Prev; 25(4); 603-12. (c)2016 AACR SEE ALL ARTICLES IN THIS CEBP FOCUS SECTION, "MULTILEVEL APPROACHES TO ADDRESSING CANCER HEALTH DISPARITIES". PMID- 27196093 TI - Results of a Multilevel Intervention Trial to Increase Human Papillomavirus (HPV) Vaccine Uptake among Adolescent Girls. AB - BACKGROUND: Uptake of the human papillomavirus (HPV) vaccine is low in Appalachian Ohio and areas with high cervical cancer rates. METHODS: We conducted a group-randomized trial among 12 counties in Appalachian Ohio randomized to receive either an HPV vaccine (intervention counties) or influenza vaccine (comparison counties) multilevel intervention (MLI). Parents (n = 337) who had a daughter aged 9 to 17 years who had not received the HPV vaccine were recruited from commercial lists. Clinics (N = 24) and 119 providers from these clinics were also recruited. The primary outcome was medical record-confirmed receipt of the first shot of the HPV vaccine 3 months after receiving the intervention among daughters of parents enrolled in the study. Secondary outcomes included receipt of the first HPV vaccine shot by 6 months and changes in provider knowledge. RESULTS: According to medical records, 10 (7.7%) daughters of intervention participants received the first shot of the HPV vaccine within 3 months of being sent the intervention materials compared with 4 (3.2%) daughters of comparison group participants (P = 0.061). By 6 months, 17 (13.1%) daughters of intervention participants received the first HPV vaccine shot compared with eight (6.5%) daughters of comparison group participants (P = 0.002). Provider knowledge about HPV increased (P < 0.001, from baseline to after education). CONCLUSIONS: The MLI increased uptake of the HPV vaccine among girls aged 9 to 17 years; however, uptake was low. IMPACT: To improve HPV vaccine uptake, attention to additional levels of influence (e.g., policy, community) and more elements within levels (e.g., reminders, automated prompts) may be needed. Cancer Epidemiol Biomarkers Prev; 25(4); 593-602. (c)2016 AACR SEE ALL ARTICLES IN THIS CEBP FOCUS SECTION, "MULTILEVEL APPROACHES TO ADDRESSING CANCER HEALTH DISPARITIES". PMID- 27196095 TI - Coffee Consumption and the Risk of Colorectal Cancer. AB - BACKGROUND: Coffee contains several bioactive compounds relevant to colon physiology. Although coffee intake is a proposed protective factor for colorectal cancer, current evidence remains inconclusive. METHODS: We investigated the association between coffee consumption and risk of colorectal cancer in 5,145 cases and 4,097 controls from the Molecular Epidemiology of Colorectal Cancer (MECC) study, a population-based case-control study in northern Israel. We also examined this association by type of coffee, by cancer site (colon and rectum), and by ethnic subgroup (Ashkenazi Jews, Sephardi Jews, and Arabs). Coffee data were collected by interview using a validated, semi-quantitative food frequency questionnaire. RESULTS: Coffee consumption was associated with 26% lower odds of developing colorectal cancer [OR (drinkers vs. non-drinkers), 0.74; 95% confidence interval (CI), 0.64-0.86; P < 0.001]. The inverse association was also observed for decaffeinated coffee consumption alone (OR, 0.82; 95% CI, 0.68-0.99; P = 0.04) and for boiled coffee (OR, 0.82; 95% CI, 0.71-0.94; P = 0.004). Increasing consumption of coffee was associated with lower odds of developing colorectal cancer. Compared with <1 serving/day, intake of 1 to <2 servings/day (OR, 0.78; 95% CI, 0.68-0.90; P < 0.001), 2 to 2.5 servings/day (OR, 0.59; 95% CI, 0.51-0.68; P < 0.001), and >2.5 servings/day (OR, 0.46; 95% CI, 0.39-0.54; P < 0.001) were associated with significantly lower odds of colorectal cancer (Ptrend < 0.001), and the dose-response trend was statistically significant for both colon and rectal cancers. CONCLUSIONS: Coffee consumption may be inversely associated with risk of colorectal cancer in a dose-response manner. IMPACT: Global coffee consumption patterns suggest potential health benefits of the beverage for reducing the risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 25(4); 634-9. (c)2016 AACR. PMID- 27196097 TI - Bimodal Winter Haul-Out Patterns of Adult Weddell Seals (Leptonychotes weddellii) in the Southern Weddell Sea. AB - Hauling out is an essential component of pinniped life-history. Haul-out behaviour may be affected by biological (e.g. sex, age and condition) and physical factors (e.g. food availability and environmental conditions), and identifying these factors may help explain the spatio-temporal distribution and habitat use of pinnipeds. The aim of this study is to describe observed winter haul-out patterns of adult Weddell seals in the Weddell Sea and investigate the role of potential predictors to gain insight into the way these animals interact with the physical environment in this region. We examined the haul-out behaviour in relation to available biological (i.e., diving effort, sex) and physical information (i.e., sun angle). Thirty-three satellite telemetry tags were deployed on adult Weddell seals in the southern Weddell Sea during February 2007, 2009 and 2011, following their annual moult recording information on the behavioural mode of the animal: at surface, hauled out or diving. At the end of the austral summer Weddell seals spent, on average, more than 40% of their time hauled out on the ice. Under constant light conditions, it appears that physiological factors drive sex differences in the timing and duration of haul out behaviour, with females spending on average more time hauled out than males during daylight hours. This time spent hauled-out declined to around 15% in both sexes by the beginning of autumn and remained at this level with a clear nocturnal haul-out pattern during the winter. The time spent diving increased during this period, indicating an increase in foraging effort during the winter months, and led to a common haul-out pattern in both sexes over winter. We found a positive relationship between haul-out duration and the percentage of time spent diving prior to a haul-out in both sexes, with the exception of female daytime haul-outs early in the year. PMID- 27196096 TI - ROS Involves the Fungicidal Actions of Thymol against Spores of Aspergillus flavus via the Induction of Nitric Oxide. AB - Aspergillus flavus is a well-known pathogenic fungus for both crops and human beings. The acquisition of resistance to azoles by A. flavus is leading to more failures occurring in the prevention of infection by A. flavus. In this study, we found that thymol, one of the major chemical constituents of the essential oil of Monarda punctate, had efficient fungicidal activity against A. flavus and led to sporular lysis. Further studies indicated that thymol treatment induced the generation of both ROS and NO in spores, whereas NO accumulation was far later than ROS accumulation in response to thymol. By blocking ROS production with the inhibitors of NADPH oxidase, NO generation was also significantly inhibited in the presence of thymol, which indicated that ROS induced NO generation in A. flavus in response to thymol treatment. Moreover, the removal of either ROS or NO attenuated lysis and death of spores exposed to thymol. The addition of SNP (exogenous NO donor) eliminated the protective effects of the inhibitors of NADPH oxidase on thymol-induced lysis and death of spores. Taken together, it could be concluded that ROS is involved in spore death induced by thymol via the induction of NO. PMID- 27196098 TI - Dynamic Dazzle Distorts Speed Perception. AB - Static high contrast ('dazzle') patterns, such as zigzags, have been shown to reduce the perceived speed of an object. It has not escaped our notice that this effect has possible military applications and here we report a series of experiments on humans, designed to establish whether dynamic dazzle patterns can cause distortions of perceived speed sufficient to provide effective defence in the field, and the extent to which these effects are robust to a battery of manipulations. Dynamic stripe patterns moving in the same direction as the target are found to increase the perceived speed of that target, whilst dynamic stripes moving in the opposite direction to the target reduce the perceived speed. We establish the optimum position for such dazzle patches; confirm that reduced contrast and the addition of colour do not affect the performance of the dynamic dazzle, and finally, using the CO2 challenge, show that the effect is robust to stressful conditions. PMID- 27196099 TI - Possible evolutionary origins of human female sexual fluidity. AB - I propose an evolutionary theory of human female sexual fluidity and argue that women may have been evolutionarily designed to be sexually fluid in order to allow them to have sex with their cowives in polygynous marriage and thus reduce conflict and tension inherent in such marriage. In addition to providing an extensive definition and operationalization of the concept of sexual fluidity and specifying its ultimate function for women, the proposed theory can potentially solve several theoretical and empirical puzzles in evolutionary psychology and sex research. Analyses of the National Longitudinal Study of Adolescent Health (Add Health) confirm the theory's predictions that: (i) women (but not men) who experience increased levels of sexual fluidity have a larger number of children (suggesting that female sexual fluidity, if heritable, may be evolutionarily selected); (ii) women (but not men) who experience marriage or parenthood early in adult life subsequently experience increased levels of sexual fluidity; and (iii) sexual fluidity is significantly positively correlated with known markers of unrestricted sexual orientation among women whereas it is significantly negatively correlated with such markers among men. PMID- 27196100 TI - Complexities and Perplexities: A Critical Appraisal of the Evidence for Soil Transmitted Helminth Infection-Related Morbidity. AB - BACKGROUND: Soil-transmitted helminths (STH) have acute and chronic manifestations, and can result in lifetime morbidity. Disease burden is difficult to quantify, yet quantitative evidence is required to justify large-scale deworming programmes. A recent Cochrane systematic review, which influences Global Burden of Disease (GBD) estimates for STH, has again called into question the evidence for deworming benefit on morbidity due to STH. In this narrative review, we investigate in detail what the shortfalls in evidence are. METHODOLOGY/PRINCIPAL FINDINGS: We systematically reviewed recent literature that used direct measures to investigate morbidity from STH and we critically appraised systematic reviews, particularly the most recent Cochrane systematic review investigating deworming impact on morbidity. We included six systematic reviews and meta-analyses, 36 literature reviews, 44 experimental or observational studies, and five case series. We highlight where evidence is insufficient and where research needs to be directed to strengthen morbidity evidence, ideally to prove benefits of deworming. CONCLUSIONS/SIGNIFICANCE: Overall, the Cochrane systematic review and recent studies indicate major shortfalls in evidence for direct morbidity. However, it is questionable whether the systematic review methodology should be applied to STH due to heterogeneity of the prevalence of different species in each setting. Urgent investment in studies powered to detect direct morbidity effects due to STH is required. PMID- 27196101 TI - Histone Modification Is Involved in Okadaic Acid (OA) Induced DNA Damage Response and G2-M Transition Arrest in Maize. AB - Histone modifications are involved in regulation of chromatin structure. To investigate the relationship between chromatin modification and cell cycle regulation during plant cell proliferation, Okadaic acid (OA), a specific inhibitor of serine/threonine protein phosphatase, was applied in this study. The results showed that OA caused the cell cycle arrest at preprophase, leading to seedling growth inhibition. Western blotting assay revealed that the spatial distribution of phosphorylation of Ser10 histone H3 tails (H3S10ph) signals was altered under OA treatment. Reactive oxygen species (ROS) was found to be at higher levels and TdT-mediated dUTP nick end labeling (TUNEL) assay displayed DNA breaks happened at the chromatin after treatment with OA, companied with an increase in the acetylation of histone H4 at lysine 5 (H4K5ac) level. From these observations, we speculated that the alteration of the spatial distribution of H3S10ph and the level of H4K5ac was involved in the procedure that OA induced DNA breaks and G2-M arrested by the accumulation of ROS, and that the histone H3S10ph and H4K5ac might facilitate DNA repair by their association with the chromatin decondensation. PMID- 27196102 TI - Provider-Initiated Late Preterm Births in Brazil: Differences between Public and Private Health Services. AB - BACKGROUND: A large proportion of the rise in prematurity worldwide is owing to late preterm births, which may be due to the expansion of obstetric interventions, especially pre-labour caesarean section. Late preterm births pose similar risks to overall prematurity, making this trend a concern. In this study, we describe factors associated with provider-initiated late preterm birth and verify differences in provider-initiated late preterm birth rates between public and private health services according to obstetric risk. METHODS: This is a sub analysis of a national population-based survey of postpartum women entitled "Birth in Brazil", performed between 2011 and 2012. We included 23,472 singleton live births. We performed non-conditional multiple logistic regressions assessing associated factors and analysing differences between public and private health services. RESULTS: Provider-initiated births accounted for 38% of late preterm births; 32% in public health services and 61% in private health services. They were associated with previous preterm birth(s) and maternal pathologies for women receiving both public and private services and with maternal age >=35 years for women receiving public services. Women receiving private health services had higher rates of provider-initiated late preterm birth (rate of 4.8%) when compared to the ones receiving public services (rate of 2.4%), regardless of obstetric risk-adjusted OR of 2.3 (CI 1.5-3.6) for women of low obstetric risk and adjusted OR of 1.6 (CI 1.1-2.3) for women of high obstetric risk. CONCLUSION: The high rates of provider-initiated late preterm birth suggests a considerable potential for reduction, as such prematurity can be avoided, especially in women of low obstetric risk. To promote healthy births, we advise introducing policies with incentives for the adoption of new models of birth care. PMID- 27196105 TI - Effect of age, decentration, aberrations and pupil size on subjective image quality with concentric bifocal optics. AB - PURPOSE: We investigated the impact of lens centration, wearer aberrations, pupil size and age on the optics of two bifocal contact lenses using image simulation. METHOD: Fourteen conditions (i.e. two optical profiles with two and eight concentric zones; two conditions of centration: centred and 0.77 mm decentred; and three conditions of aberrations: 0, 0.15 and 0.35 MUm RMS; three pupil sizes: 3, 4.5 and 6 mm) were tested on two populations (i.e. 20-40 and 40-60 years old) using a numerical simulation method. For each condition, images were calculated for proximities ranging from -4D to + 2D with steps of 0.25D. Subjects graded the quality of each simulated image (i.e. a target 'HEV' of 0.4 logMAR) on a continuous scale from 0 to 5. To limit the effect of the observer's own aberrations, subjects viewed the displayed images through a 3-mm pupil and their optimal correction. RESULTS: Both populations reported similar image quality (i.e. average absolute difference of 0.23) except for sharp and low contrast images, which obtained slightly higher grades with younger subjects, probably due to a better contrast sensitivity in this population. Typical decentration had no effect on bifocal contact lenses wearers' vision, as the ratio between areas dedicated to near and distance vision did not change. Aberrations (i.e. mainly 0.24 MUm of spherical aberration on a 4.5-mm pupil) reduced the addition of the two radial zones bifocal optics and introduced a hyperopic shift (i.e. 0.50D) of the through-focus image quality for the eight radial zone bifocal lens. The combination of typical aberrations with typical decentration created the same effect as typical aberrations alone, meaning that aberration impact was stronger than decentration impact. The two radial zone bifocal lens was dependent on the pupil whereas the eight radial zone lens was not. CONCLUSIONS: When fitting new bifocal optics, the aberrations of the patients, as well as their pupil diameter, are the main subject dependent parameters influencing quality of vision. Typical contact lens decentration and lower cortical treatment efficiency of retinal images of older subjects had relatively little impact. PMID- 27196103 TI - Thrombospondin 1 Deficiency Ameliorates the Development of Adriamycin-Induced Proteinuric Kidney Disease. AB - Accumulating evidence suggests that thrombospondin 1 (TSP1) is an important player in diabetic nephropathy. However, the role of TSP1 in podocyte injury and the development of non-diabetic proteinuric kidney disease is largely unknown. In the current study, by using a well-established podocyte injury model (adriamycin induced nephropathy mouse model), we examined the contribution of TSP1 to the development of proteinuric kidney disease. We found that TSP1 was up-regulated in the glomeruli, notably in podocytes, in adriamycin injected mice before the onset of proteinuria. ADR treatment also stimulated TSP1 expression in cultured human podocytes in vitro. Moreover, increased TSP1 mediated ADR-induced podocyte apoptosis and actin cytoskeleton disorganization. This TSP1's effect was through a CD36-dependent mechanism and involved in the stimulation of p38MAPK pathway. Importantly, in vivo data demonstrated that TSP1 deficiency protected mice from ADR induced podocyte loss and foot process effacement. ADR induced proteinuria, glomerulosclerosis, renal macrophage infiltration and inflammation was also attenuated in TSP1 deficient mice. Taken together, these studies provide new evidence that TSP1 contributes to the development of non-diabetic proteinuric kidney disease by stimulating podocyte injury and the progression of renal inflammation. PMID- 27196106 TI - Macrophages: A review of their role in wound healing and their therapeutic use. AB - Macrophages are mononuclear phagocytes established during embryogenesis and derived from the yolk sac or the fetal liver but also recruited from the blood and bone marrow under proliferative inflammatory conditions (such as tissue repair). Most importantly, they take on distinct phenotypes and functions crucial to healing upon localization in the wound. The objective of this review is to summarize recent findings in regard to the cellular mechanisms of macrophages and chronic wounds. Advances in the potential use of macrophage therapy have arisen based, in part, on the fact that early recruitment of macrophages is critical to wound healing. Higher quality evidence is needed to support the use of macrophage therapy for chronic wound types, as is a better understanding of the signaling related to macrophage polarization, activation of macrophages, and their effect of mechanisms of repair. An evaluation of the currently available research on mechanism of action may lead to a better understanding of the signaling processes of the many macrophage phenotypes, as well as their roles and outcomes in wound healing, which could then guide the development and eventual widespread use of macrophage therapies. PMID- 27196104 TI - Associations of Hospital and Patient Characteristics with Fluid Resuscitation Volumes in Patients with Severe Sepsis: Post Hoc Analyses of Data from a Multicentre Randomised Clinical Trial. AB - PURPOSE: Fluid resuscitation is a key intervention in patients with sepsis and circulatory impairment. The recommendations for continued fluid therapy in sepsis are vague, which may result in differences in clinical practice. We aimed to evaluate associations between hospital and patient characteristics and fluid resuscitation volumes in ICU patients with severe sepsis. METHODS: We explored the 6S trial database of ICU patients with severe sepsis needing fluid resuscitation randomised to hydroxyethyl starch 130/0.42 vs. Ringer's acetate. Our primary outcome measure was fluid resuscitation volume and secondary outcome total fluid input administered from 24 hours before randomisation until the end of day 3 post-randomisation. We performed multivariate analyses with hospital and patient baseline characteristics as covariates to assess associations with fluid volumes given. RESULTS: We included 654 patients who were in the ICU for 3 days and had fluid volumes available. Individual trial sites administered significantly different volumes of fluid resuscitation and total fluid input after adjusting for baseline variables (P<0.001). Increased lactate, higher cardiovascular and renal SOFA subscores, lower respiratory SOFA subscore and surgery were all independently associated with increased fluid resuscitation volumes. CONCLUSIONS: Hospital characteristics adjusted for patient baseline values were associated with differences in fluid resuscitation volumes given in the first 3 days of severe sepsis. The data indicate variations in clinical practice not explained by patient characteristics emphasizing the need for RCTs assessing fluid resuscitation volumes fluid in patients with sepsis. PMID- 27196107 TI - A Biomathematical Model of Pneumococcal Lung Infection and Antibiotic Treatment in Mice. AB - Pneumonia is considered to be one of the leading causes of death worldwide. The outcome depends on both, proper antibiotic treatment and the effectivity of the immune response of the host. However, due to the complexity of the immunologic cascade initiated during infection, the latter cannot be predicted easily. We construct a biomathematical model of the murine immune response during infection with pneumococcus aiming at predicting the outcome of antibiotic treatment. The model consists of a number of non-linear ordinary differential equations describing dynamics of pneumococcal population, the inflammatory cytokine IL-6, neutrophils and macrophages fighting the infection and destruction of alveolar tissue due to pneumococcus. Equations were derived by translating known biological mechanisms and assuming certain response kinetics. Antibiotic therapy is modelled by a transient depletion of bacteria. Unknown model parameters were determined by fitting the predictions of the model to data sets derived from mice experiments of pneumococcal lung infection with and without antibiotic treatment. Time series of pneumococcal population, debris, neutrophils, activated epithelial cells, macrophages, monocytes and IL-6 serum concentrations were available for this purpose. The antibiotics Ampicillin and Moxifloxacin were considered. Parameter fittings resulted in a good agreement of model and data for all experimental scenarios. Identifiability of parameters is also estimated. The model can be used to predict the performance of alternative schedules of antibiotic treatment. We conclude that we established a biomathematical model of pneumococcal lung infection in mice allowing predictions regarding the outcome of different schedules of antibiotic treatment. We aim at translating the model to the human situation in the near future. PMID- 27196108 TI - Evaluation of the Effect of Diagnostic Molecular Testing on the Surgical Decision Making Process for Patients With Thyroid Nodules. AB - IMPORTANCE: Diagnostic molecular testing is used in the workup of thyroid nodules. While these tests appear to be promising in more definitively assigning a risk of malignancy, their effect on surgical decision making has yet to be demonstrated. OBJECTIVE: To investigate the effect of diagnostic molecular profiling of thyroid nodules on the surgical decision-making process. DESIGN, SETTING, AND PARTICIPANTS: A surgical management algorithm was developed and published after peer review that incorporated individual Bethesda System for Reporting Thyroid Cytopathology classifications with clinical, laboratory, and radiological results. This algorithm was created to formalize the decision-making process selected herein in managing patients with thyroid nodules. Between April 1, 2014, and March 31, 2015, a prospective study of patients who had undergone diagnostic molecular testing of a thyroid nodule before being seen for surgical consultation was performed. The recommended management undertaken by the surgeon was then prospectively compared with the corresponding one in the algorithm. Patients with thyroid nodules who did not undergo molecular testing and were seen for surgical consultation during the same period served as a control group. MAIN OUTCOMES AND MEASURES: All pertinent treatment options were presented to each patient, and any deviation from the algorithm was recorded prospectively. To evaluate the appropriateness of any change (deviation) in management, the surgical histopathology diagnosis was correlated with the surgery performed. RESULTS: The study cohort comprised 140 patients who underwent molecular testing. Their mean (SD) age was 50.3 (14.6) years, and 75.0% (105 of 140) were female. Over a 1-year period, 20.3% (140 of 688) had undergone diagnostic molecular testing before surgical consultation, and 79.7% (548 of 688) had not undergone molecular testing. The surgical management deviated from the treatment algorithm in 12.9% (18 of 140) with molecular testing and in 10.2% (56 of 548) without molecular testing (P = .37). In the group with molecular testing, the surgical management plan of only 7.9% (11 of 140) was altered as a result of the molecular test. All but 1 of those patients were found to be overtreated relative to the surgical histopathology analysis. CONCLUSIONS AND RELEVANCE: Molecular testing did not significantly affect the surgical decision-making process in this study. Among patients whose treatment was altered based on these markers, there was evidence of overtreatment. PMID- 27196109 TI - Immunizing against Anogenital Cancer: HPV Vaccines. PMID- 27196111 TI - Microwave and Quantum Chemical Study of Intramolecular Hydrogen Bonding in 2 Propynylhydrazine (HC=CCH2NHNH2). AB - The microwave spectrum of 2-propynylhydrazine (HC=CCH2NHNH2) was investigated in the 23-124 GHz spectral interval. The spectra of two conformers denoted I and II were assigned. I is the lower-energy form, and relative intensity measurements yielded an internal energy difference of 3.0(4) kJ/mol between I and II. The spectra of the ground and five vibrationally excited states were assigned for I, whereas only the spectrum of the ground vibrational state was assigned for II. Both I and II are each stabilized simultaneously by two intramolecular hydrogen bonds. The first of these hydrogen bonds is formed between the hydrogen atom of the -NH- part of the hydrazino group, and the second internal hydrogen bond is formed between one of the hydrogen atoms of the -NH2 part. The pi-electrons of the triple bond is thus shared by these two hydrogen atoms. The shortest contact between a hydrogen atom of the hydrazino group and the pi-electrons of the ethynyl group is found in lower-energy conformer I. The conformational properties of 2-propynylhydrazine were explored by MP2/cc-pVTZ and CCSD/cc-pVQZ calculations. The CCSD method predicts that seven rotameric forms exist for this compound. Five of these rotamers are stabilized by internal hydrogen bonding. The simultaneous sharing of the pi-electrons of the triple bond by two hydrogen atoms occurs only in Conformers I and II, which are predicted to be the two forms with the lowest energies, with I 2.52 kJ/mol lower in energy than II. The effective rotational constants of the ground vibrational states of I and II were predicted by a combination of MP2 and CCSD calculations, whereas centrifugal distortion constants and vibration-rotation constants were calculated by the MP2 method. The theoretical spectroscopic constants are compared with the experimental counterparts. It is concluded that more refined calculations are necessary to obtain complete agreement. PMID- 27196112 TI - Control of the threshold voltage in ZnO nanobelt field-effect transistors by using MoO x thin film. AB - We report on the feasible control of the threshold voltage (V th) in ultra-thin ZnO nanobelt FETs by using substoichiometric molybdenum trioxide (MoO x , x < 3) either as a modification layer on the surface of ZnO nanobelts or as electrodes instead of the widely used Ti/Au. ZnO nanobelt FETs using Ti/Au as the electrodes usually exhibit a negative threshold voltage, indicating n-channel depletion mode behavior, whereas ZnO FETs with MoO x /Au electrodes instead of Ti/Au show a positive shift of threshold voltage, exhibiting an n-channel type enhancement mode, which can be explained by a high Schottky barrier created at the interface of MoO x and the ZnO channel. In contrast, the decoration on the surface of ZnO channel by MoO x significantly increases the zero-bias conductivity and electron carrier concentration, and then negatively shifts the threshold voltage. We propose that MoO x thin film may play a passivation effect role, much more so than the doping effect role, due to the large amount of adsorbed species on as grown ZnO nanobelts, especially oxygen species. PMID- 27196110 TI - Coinfections of the Respiratory Tract: Viral Competition for Resources. AB - Studies have shown that simultaneous infection of the respiratory tract with at least two viruses is common in hospitalized patients, although it is not clear whether these infections are more or less severe than single virus infections. We use a mathematical model to study the dynamics of viral coinfection of the respiratory tract in an effort to understand the kinetics of these infections. Specifically, we use our model to investigate coinfections of influenza, respiratory syncytial virus, rhinovirus, parainfluenza virus, and human metapneumovirus. Our study shows that during coinfections, one virus can block another simply by being the first to infect the available host cells; there is no need for viral interference through immune response interactions. We use the model to calculate the duration of detectable coinfection and examine how it varies as initial viral dose and time of infection are varied. We find that rhinovirus, the fastest-growing virus, reduces replication of the remaining viruses during a coinfection, while parainfluenza virus, the slowest-growing virus is suppressed in the presence of other viruses. PMID- 27196113 TI - Educating teenagers about hearing health by training them to educate children. AB - OBJECTIVE: We investigated the change in hearing-health behaviour amongst teenagers trained to deliver the Dangerous Decibels programme to younger children. DESIGN: The Dangerous Decibels programme uses a two-stage process to train 8-12 year-old children to protect their hearing from noise: (1) a team of experts train 'Educators' who (2) give classroom training to children in schools. Training teenagers as Educators may add a second level of benefit if teenagers internalize the hearing-health messages that they present and thus protect their own hearing better. They were assessed before training, immediately after, and three months later (after all had presented the classroom training) using a questionnaire. In addition, a focus group was conducted with a subgroup of the Educators to assess their subjective experience. STUDY SAMPLE: We trained 44 Educators aged 14-17 years. RESULTS: Results were generally positive: there were significant and sustained improvements in knowledge, self-reported behaviour, and perceived supports towards protecting hearing, and trends but not significant changes in attitudes or perceived barriers to hearing protection. CONCLUSIONS: Providing training to teenagers had benefits beyond the delivery of training to younger children, but improvements in the delivery model may increase the uptake and impact on the teenagers. PMID- 27196114 TI - Aqueous chlorine dioxide treatment of horticultural produce: Effects on microbial safety and produce quality-A review. AB - Microbial load on fresh fruit and vegetables causes decay and losses after harvest and may lead to foodborne illness in case of contamination with human pathogens on raw consumed produces. Washing with tap water only marginally reduces microorganisms attached to produce surfaces. Chlorine is widely used for decontamination on fresh horticultural produces. However, due to harmful by products and the questionable efficacy it has become increasingly challenged. During the last 20 years, the interest to study ClO2 treatments as an alternative sanitation agent for industrially prepared fresh produce has largely increased. For a wide range of commodities, the application of gaseous ClO2 has meanwhile been investigated. In addition, since several years, the interest in aqueous ClO2 treatments has further risen because of the better manageability in postharvest processing lines compared to gaseous application. This article critically evaluated the effects of postharvest application of aqueous ClO2, either alone or in combination with other treatments, on microbial loads for various horticultural produces. In laboratory investigations, application of aqueous ClO2 at concentrations between 3 and 100 ppm effectively reduced counts of natural or inoculated microorganisms (bacteria, yeasts, and mold) in the range of 1 and 5 log. However, various effects of ClO2 treatments on produce quality have been described. These mainly comprise implication on sensory and visual attributes. In this context, there is increasing focus on the potential impacts of aqueous ClO2 on relevant nutritional components of produces such as organic acids or phenolic substances. PMID- 27196115 TI - Revisiting the revisit: added evidence for a social chemosignal in human emotional tears. AB - In a study by Gelstein et al., we found that human emotional tears act as a social chemosignal. In the first of three different experiments in that study we observed that sniffing women's emotional tears reduced the sexual attractiveness attributed by men to pictures of women's faces. In a study partly titled "Chemosignaling effects of human tears revisited", Gracanin et al. claim failed replication of this effect in a series of experiments, one they described as "exactly the same procedure" as Gelstein. Given that Gracanin et al. refused our extended offer to jointly replicate the experiment at our expense, we can merely comment on their effort. We find that Gracanin, who are not a chemosignaling laboratory, used methodology that falls short of standards typically applied in chemosignaling research. Thus, their experiments were profoundly different from Gelstein. Finally, we found that in reanalysing their raw data we could in fact replicate the effect from Gelstein. Thus, we conclude that the failed replication in Gracanin is neither a replication nor failed. PMID- 27196117 TI - Silent AF and Hypertrophic Stroke Risk: More Data, More Monitoring. PMID- 27196116 TI - PD-L1 testing for lung cancer in the UK: recognizing the challenges for implementation. AB - A new approach to the management of non-small-cell lung cancer (NSCLC) has recently emerged that works by manipulating the immune checkpoint controlled by programmed death receptor 1 (PD-1) and its ligand programmed death ligand 1 (PD L1). Several drugs targeting PD-1 (pembrolizumab and nivolumab) or PD-L1 (atezolizumab, durvalumab, and avelumab) have been approved or are in the late stages of development. Inevitably, the introduction of these drugs will put pressure on healthcare systems, and there is a need to stratify patients to identify those who are most likely to benefit from such treatment. There is evidence that responsiveness to PD-1 inhibitors may be predicted by expression of PD-L1 on neoplastic cells. Hence, there is considerable interest in using PD-L1 immunohistochemical staining to guide the use of PD-1-targeted treatments in patients with NSCLC. This article reviews the current knowledge about PD-L1 testing, and identifies current research requirements. Key factors to consider include the source and timing of sample collection, pre-analytical steps (sample tracking, fixation, tissue processing, sectioning, and tissue prioritization), analytical decisions (choice of biomarker assay/kit and automated staining platform, with verification of standardized assays or validation of laboratory devised techniques, internal and external quality assurance, and audit), and reporting and interpretation of the results. This review addresses the need for integration of PD-L1 immunohistochemistry with other tests as part of locally agreed pathways and protocols. There remain areas of uncertainty, and guidance should be updated regularly as new information becomes available. PMID- 27196118 TI - Managers as role models for health: Moderators of the relationship of transformational leadership with employee exhaustion and cynicism. AB - Drawing on social learning literature, this study examined managers' health awareness and health behavior (health-related self-regulation) as a moderator of the relationships between transformational leadership and employee exhaustion and cynicism. In 2 organizations, employees (n = 247; n = 206) rated their own exhaustion and cynicism, and their managers' transformational leadership. Managers (n = 57; n = 30) assessed their own health-related self-regulation. Multilevel modeling showed that, as expected, managers' health awareness moderated the relationship between transformational leadership and employee exhaustion and cynicism. Employees experienced less exhaustion and cynicism when transformational leaders were aware of their own health. Managers' health behavior moderated the relationship between transformational leadership and employee exhaustion in 1 organization, but not in the other. With respect to health behavior, we found no significant results for employee cynicism. In sum, the results indicate that when managers are role models for health, employees will benefit more from the transformational leadership style. (PsycINFO Database Record PMID- 27196119 TI - Otoscopic diagnosis of otitis media. AB - Accurate diagnosis of otitis media is important to prevent suffering and complications when infection is present, and unnecessary antibiotic use when infection is absent. The usual signs and symptoms of acute otitis media are unreliable guides in infants and young children. Similarly, middle ear effusions may present with little discomfort in older children. We therefore depend on examination of the tympanic membrane with an otoscope to make most diagnoses. This article aims to improve the accuracy of middle ear diagnosis by pneumatic otoscopy. It includes descriptions and photographs of the normal ear drum and illustrates the pathologic changes seen in acute otitis media, long-standing eustachian tube dysfunction and otitis media with effusion. PMID- 27196120 TI - Outcomes in coeliac disease: a qualitative exploration of patients' views on what they want to achieve when seeing a dietitian. AB - BACKGROUND: Coeliac disease (CD) is managed by life-long adherence to a gluten free diet and dietitians have the potential to facilitate this. Patient involvement through shared decision-making is central to behaviour-change skills used by dietitians, although there is little evidence supporting its inclusion in evaluating dietetic interventions. The present study aimed to explore patients' preferences for diet and nutrition-related outcomes in CD. METHODS: Adults with CD or adult carers of children with CD were invited through support networks. Participants took part in a telephone, face-to-face interview or focus group which was audio-recorded and transcribed. Themes were developed using a framework method. Ethical approval was obtained. RESULTS: Twenty-nine adult patients and five parents of CD children participated 0-34 years after diagnosis. Four main outcome-related themes emerged: (i) Participants wanted information specific to their lifestyle and time since diagnosis, focussing on food containing gluten, practical issues, prescribable items and general nutrition. (ii) The degree of satisfaction with the consultation process impacted on participants' experience, including the dietitian's CD expertise, consistency of the dietitian seen, and the frequency and length of appointments. (iii) Health concerns were important to participants and focussed on risk of osteoporosis, unwanted weight gain, and the fat and sugar content of manufactured gluten-free products. (iv) Clinical monitoring, including bone scans and antibody measurements, was mentioned but was not described as being of importance for most participants. CONCLUSIONS: The outcomes preferred by CD patients and carers focussed primarily on information and resources received and satisfaction with their dietetic consultation. PMID- 27196122 TI - Synthesis of Chiral Fluorinated Hydrazines via Pd-Catalyzed Asymmetric Hydrogenation. AB - An enantioselective hydrogenation of fluorinated hydrazones has been achieved by employing [Pd(R)-DTBM-SegPhos(OCOCF3)2] as the catalyst, providing a general and convenient method toward chiral fluorinated hydrazines. A broad substrate scope including beta-aryl-, gamma-aryl-, and alkyl-chain-substituted hydrazones worked efficiently in high yields and up to 94% of enantioselectivity. The reductive amination between trifluoromethyl-substituted ketones and benzohydrazides could also proceed smoothly. PMID- 27196121 TI - Intranasal Dexmedetomidine as a Sedative Premedication for Patients Undergoing Suspension Laryngoscopy: A Randomized Double-Blind Study. AB - BACKGROUND: Intranasal dexmedetomidine, a well-tolerated and convenient treatment option, has been shown to induce a favorable perioperative anxiolysis in children. We investigate intranasal dexmedetomidine as a sedative premedication for anesthesia recovery in an adult population. METHODS: A prospective randomized controlled trial; 81 adult patients scheduled for elective suspension laryngoscopy received intranasal dexmedetomidine (1 MUg?kg-1) or a placebo 45-60 min before anesthetic induction. Extubation time was used as the primary outcome measure. Secondary variables included the levels of sedation (Observer's Assessment of Alertness/Sedation scale, OAA/S) and anxiety (4-point anxiety score), anesthetic and analgesic requirements, hemodynamic fluctuations, and anesthesia recovery as well as side effects. RESULTS: The levels of sedation and anxiety differed significantly between the two groups at anesthesia pre-induction (p < 0.001 and = 0.001, respectively). Repeated-measure general linear model determined no significant interaction effect between group and time on the targeted concentration of propofol (F = 1.635, p = 0.200), but a significant main effect of group existed (F = 6.880, p = 0.010). A moderate but significant decrease in the heart rate was recorded in the dexmedetomidine group at pre induction. Episodes of tachycardia and hypertension after tracheal intubation and extubation were more frequent in the placebo group. CONCLUSIONS: Intranasal dexmedetomidine as a sedative premedication induced a favorable perioperative anxiolysis without prolongation in anesthesia recovery; the hemodynamic effect was modest. TRIAL REGISTRATION: ClinicalTrials.gov NCT 02108171. PMID- 27196123 TI - Analysis of the Proteins Secreted from the Oryza meyeriana Suspension-Cultured Cells Induced by Xanthomonas oryzae pv. oryzae. AB - Oryza meyeriana, a wild species of rice from China, shows high resistance to Xanthomonas oryzae pv. oryzae (Xoo), the cause of rice bacterial blight, one of the most serious rice pathogens. To better understand the resistance mechanism, a proteomic study was conducted to identify changes in the proteins secreted in embryo cell suspension cultures in response to Xoo. After two-dimensional difference gel electrophoresis (2D-DIGE), 72 differentially expressed protein spots corresponding to 34 proteins were identified by Matrix-Assisted Laser Desorption/ Ionization Time of Flight Mass Spectrometry. Of the 34 proteins, 10 were up regulated and 24 down regulated. The secreted proteins identified were predicted to be involved in various biological processes, including signal transduction, defense, ROS and cell wall modification. 77% of the 34 proteins were predicted to have a signal peptide by Signal P. Quantitative Real-Time PCR showed that transcript levels of 14 secreted proteins were not well correlated with secreted protein levels. Peroxidase activity was up regulated in both O. meyriana and susceptible rice but was about three times higher in O. meyeriana. This suggests that peroxidases may play an important role in the early response to Xoo in O. meyeriana. These results not only provide a better understanding of the resistance mechanism of O. meyeriana, but have implications for studies of the interactions between other plants and their pathogens. PMID- 27196125 TI - Structural insight into antibody-mediated antagonism of the Glucagon-like peptide 1 Receptor. AB - The Glucagon-like peptide-1 receptor (GLP-1R) is a member of the class B G protein-coupled receptor (GPCR) family and a well-established target for the treatment of type 2 diabetes. The N-terminal extracellular domain (ECD) of GLP-1R is important for GLP-1 binding and the crystal structure of the GLP-1/ECD complex was reported previously. The first structure of a class B GPCR transmembrane (TM) domain was solved recently, but the full length receptor structure is still not well understood. Here we describe the molecular details of antibody-mediated antagonism of the GLP-1R using both in vitro pharmacology and x-ray crystallography. We showed that the antibody Fab fragment (Fab 3F52) blocked the GLP-1 binding site of the ECD directly and thereby acts as a competitive antagonist of native GLP-1. Interestingly, Fab 3F52 also blocked a short peptide agonist believed to engage primarily the transmembrane and extracellular loop region of GLP-1R, whereas functionality of an allosteric small-molecule agonist was not inhibited. This study has implications for the structural understanding of the GLP-1R and related class B GPCRs, which is important for the development of new and improved therapeutics targeting these receptors. PMID- 27196127 TI - Plasmablastic Richter transformation as a resistance mechanism for chronic lymphocytic leukaemia treated with BCR signalling inhibitors. PMID- 27196124 TI - Effect of Dietary Fibers on Cecal Microbiota and Intestinal Tumorigenesis in Azoxymethane Treated A/J Min/+ Mice. AB - Foods naturally high in dietary fiber are generally considered to protect against development of colorectal cancer (CRC). However, the intrinsic effect of dietary fiber on intestinal carcinogenesis is unclear. We used azoxymethane (AOM) treated A/J Min/+ mice, which developed a significantly higher tumor load in the colon than in the small intestine, to compare the effects of dietary inulin (IN), cellulose (CE) or brewers spent grain (BSG) on intestinal tumorigenesis and cecal microbiota. Each fiber was tested at two dose levels, 5% and 15% (w/w) content of the AIN-93M diet. The microbiota was investigated by next-generation sequencing of the 16S rRNA gene (V4). We found that mice fed IN had approximately 50% lower colonic tumor load than mice fed CE or BSG (p<0.001). Surprisingly, all three types of fiber caused a dose dependent increase of colonic tumor load (p<0.001). The small intestinal tumor load was not affected by the dietary fiber interventions. Mice fed IN had a lower bacterial diversity than mice fed CE or BSG. The Bacteroidetes/Firmicutes ratio was significantly (p = 0.003) different between the three fiber diets with a higher mean value in IN fed mice compared with BSG and CE. We also found a relation between microbiota and the colonic tumor load, where many of the operational taxonomic units (OTUs) related to low tumor load were significantly enriched in mice fed IN. Among the OTUs related to low tumor load were bacteria affiliated with the Bacteroides genus. These results suggest that type of dietary fiber may play a role in the development of CRC, and that the suppressive effect of IN on colonic tumorigenesis is associated with profound changes in the cecal microbiota profile. PMID- 27196128 TI - Editorial Comment to Testicular torsion-detorsion and potential therapeutic treatments: A possible role for ischemic postconditioning. PMID- 27196126 TI - The Geriatric Nutritional Risk Index Predicts Survival in Elderly Esophageal Squamous Cell Carcinoma Patients with Radiotherapy. AB - The impact of nutritional status on survival among elderly esophageal squamous cell carcinoma (ESCC) patients undergoing radiotherapy is unclear. In this study, we aimed at validating the performance of the geriatric nutritional risk index (GNRI) in predicting overall survival time in elderly ESCC patients with radiotherapy. A retrospective cohort study was conducted on 239 ESCC patients aged 60 and over admitted consecutively from January 2008 to November 2014 in the Department of Radiotherapy, Henan Tumor Hospital (Affiliated Tumor Hospital of Zhengzhou University), Zhengzhou, Henan, China. All patients were subjected to nutritional screening using GNRI, and were followed for the occurrence of lymphatic node metastasis, radiation complication and mortality. The Kaplan-Meier method with Log-rank test was used to estimate survival curves. Univariable Cox regression analysis was used to identify variables associated with overall survival time. Among the 239 patients, 184 patients (76.9%) took no nutritional risk, 32 patients (13.4%) took moderate risk of malnutrition, and 23 patients (9.7%) took a high risk of malnutrition. Univariable Cox regression showed that both high nutritional risk group and moderate nutritional risk group were significantly less likely to survive than no nutritional risk patients (hazard ratio (HR) = 1.688, 95% confidence interval (CI) = 1.019-2.798 for moderate risk group, and HR = 2.699, 95% CI = 1.512-4.819 for high risk group, respectively). The GNRI is an independent prognostic factor for overall survival time in elderly ESCC patients with radiotherapy. A GNRI <=98 can be suggested as an indicator of surviving less. PMID- 27196129 TI - Non-pungent long chain capsaicin-analogs arvanil and olvanil display better anti invasive activity than capsaicin in human small cell lung cancers. AB - The nutritional compound capsaicin inhibits the invasion of many types of human cancers. The clinical development of capsaicin as an anti-cancer drug is limited due to its unfavorable side effects like burning sensation, stomach cramps, gut pain and nausea. This study compared the anti-invasive activity of capsaicin to non-pungent long chain capsaicin analogs, namely arvanil and olvanil, in human small cell lung cancer cells. Boyden chamber invasion assays revealed that arvanil and olvanil displayed improved anti-invasive activity relative to capsaicin in human SCLC cells. The results of the Boyden chamber assay were confirmed by the spherical invasion assay, and similar results were obtained. The anti-invasive activity of arvanil, olvanil and capsaicin were independent of TRPV and CB1 receptors. Furthermore, the anti-invasive activity of arvanil, olvanil and capsaicin was mediated by the AMPK pathway. Depletion of AMPK levels by siRNA methodology abrogated the anti-invasive activity of arvanil, olvanil and capsaicin. The non-pungent capsaicin analogs arvanil and olvanil display improved anti-invasive activity relative to capsaicin in human SCLC cells. These agents may represent the second generation of capsaicin-like compounds which are more potent than the parent molecule and have a better side effect profile. PMID- 27196131 TI - More than Anecdotes: Fishers' Ecological Knowledge Can Fill Gaps for Ecosystem Modeling. AB - BACKGROUND: Ecosystem modeling applied to fisheries remains hampered by a lack of local information. Fishers' knowledge could fill this gap, improving participation in and the management of fisheries. METHODOLOGY: The same fishing area was modeled using two approaches: based on fishers' knowledge and based on scientific information. For the former, the data was collected by interviews through the Delphi methodology, and for the latter, the data was gathered from the literature. Agreement between the attributes generated by the fishers' knowledge model and scientific model is discussed and explored, aiming to improve data availability, the ecosystem model, and fisheries management. PRINCIPAL FINDINGS: The ecosystem attributes produced from the fishers' knowledge model were consistent with the ecosystem attributes produced by the scientific model, and elaborated using only the scientific data from literature. CONCLUSIONS/SIGNIFICANCE: This study provides evidence that fishers' knowledge may suitably complement scientific data, and may improve the modeling tools for the research and management of fisheries. PMID- 27196130 TI - X-ray Structure Analysis of Indazolium trans-[Tetrachlorobis(1H indazole)ruthenate(III)] (KP1019) Bound to Human Serum Albumin Reveals Two Ruthenium Binding Sites and Provides Insights into the Drug Binding Mechanism. AB - Ruthenium(III) complexes are promising candidates for anticancer drugs, especially the clinically studied indazolium trans-[tetrachlorobis(1H indazole)ruthenate(III)] (KP1019) and its analogue sodium trans [tetrachlorobis(1H-indazole)ruthenate(III)] (NKP-1339). Several studies have emphasized the likely role of human serum proteins in the transportation and accumulation of ruthenium(III) complexes in tumors. Therefore, the interaction between KP1019 and human serum albumin was investigated by means of X-ray crystallography and inductively coupled plasma mass spectrometry (ICP-MS). The structural data unambiguously reveal the binding of two ruthenium atoms to histidine residues 146 and 242, which are both located within well-known hydrophobic binding pockets of albumin. The ruthenium centers are octahedrally coordinated by solvent molecules revealing the dissociation of both indazole ligands from the ruthenium-based drug. However, a binding mechanism is proposed indicating the importance of the indazole ligands for binding site recognition and thus their indispensable role for the binding of KP1019. PMID- 27196135 TI - En Bloc Cervical Laminoplasty Using Translaminar Screws (T-laminoplasty): Novel Procedure for Preserving Midline Ligamentous Structures. AB - STUDY DESIGN: Prospectively maintained and retrospectively analyzed study. OBJECTIVE: The authors have newly developed an en bloc cervical laminoplasty using translaminar screws (T-laminoplasty) to preserve the posterior midline structures so as to maintain spinal stability and prevent postoperative axial pain and deformity. SUMMARY OF BACKGROUND DATA: Cervical laminoplasty is a popular surgical procedure for patients with multilevel compressive cervical lesions. However, several reports have noted its limitations and shortcomings. METHODS: After exposure of the posterior cervical spine with preservation of the midline ligamentous structure, en bloc laminotomy was performed and made a laminectomized block. While the laminotomized block was being lifted, the translaminar trajectory from the lamina to the contralateral lateral mass was prepared. Then a translaminar screw was inserted with suspension of the laminotomized block to expand the spinal canal, passed through the laminar spacer, and finally fixed in the contralateral lateral mass. Next, another screw was inserted into the adjacent segment from the opposite side, and further screw fixations were made in this alternating manner. RESULTS: Twenty patients underwent T-laminoplasty and 83 segments were operated upon. Clinical outcomes were statistically improved during the mean follow-up period of 19.7 months. Radiologic outcomes of cervical lordosis and range of motion were preserved with the expansion of the cross-sectional area of the spinal canal. In addition, no restenosis or laminar settlement was observed at the last follow-up. CONCLUSIONS: T-laminoplasty can be one of the surgical options for multilevel compressive cervical lesions. With midline ligamentous structures preserving the procedure, it was possible to get enough canal decompression and foraminal decompression, while obtaining good clinical and radiologic outcomes. PMID- 27196140 TI - Thermodynamic Destabilization of Ti-O Solid Solution by H2 and Deoxygenation of Ti Using Mg. AB - Reactive metals including Ti, Zr, Hf, and V, among others, have a strong chemical affinity to oxygen, which makes them difficult to produce and costly to use. It is especially challenging to produce pure or metal alloy powders of these elements when extremely low oxygen content is required, because they have high solubility for oxygen, and the solid solution of these metals with oxygen is often more stable thermodynamically than their oxides. We report a novel thermochemical approach to destabilize Ti(O) solid solutions using hydrogen, thus enabling deoxygenation of Ti powder using Mg, which has not been possible before because of the thermodynamic stability of Ti(O) solid solutions relative to MgO. The work on Ti serves as an example for other reactive metals. Both analytical modeling and experimental results show that hydrogen can indeed increase the oxygen potential of Ti-O solid solution alloys; in other words, the stability of Ti-O solid solutions is effectively decreased, thus increasing the thermodynamic driving force for Mg to react with oxygen in Ti. Because hydrogen can be easily removed from Ti by a simple heat treatment, it is used only as a temporary alloying element to destabilize the Ti-O systems. The thermodynamic approach described here is a breakthrough and is applicable to a range of different materials. This work is expected to provide an enabling solution to overcome one of the key scientific and technological hurdles to the additive manufacturing of metals, which is emerging rapidly as the future of the manufacturing industry. PMID- 27196139 TI - Early 18F-FDG PET/CT Evaluation Shows Heterogeneous Metabolic Responses to Anti EGFR Therapy in Patients with Metastatic Colorectal Cancer. AB - OBJECTIVE: The aim of this pilot study was to explore intrapatient mixed metabolic response and early 18F-FDG PET response evaluation using predefined quantification strategies in patients with advanced KRAS wild-type colorectal adenocarcinoma (mCRC) treated with cetuximab. METHODS: A 18F-FDG PET was performed at baseline and after 2 cycles of cetuximab. Metabolic response was categorized using thresholds suggested in PERCIST. Quantitative analysis was done for the sum of all target lesions, <= 5 lesions and the metabolically most active lesion per PET. Quantitative data were correlated with clinical benefit, according to RECIST v1.1, after two months of treatment. RESULTS: In nine evaluable patients the total number of target lesions was 34 (1-8 per patient). Mixed metabolic response was observed in three out of seven patients with multiple target lesions, using TLG. Dichotomised metabolic data of the sum of all or <= 5 lesions had a concordance with clinical benefit of 89% using SULmax or SULpeak, and 100% using TLG. Evaluating the metabolically most active lesion, concordance was 89% for all three units. Additionally, the decrease in TLG was significantly correlated with PFS for all three quantification strategies. CONCLUSION: Mixed metabolic response was observed in nearly half of the patients with advanced KRAS wild-type mCRC treated with cetuximab. If <= 5 target lesions were evaluated using TLG clinical benefit was predicted correctly for all patients. Moreover, decrease in TLG is significantly correlated with the duration of PFS. Validation of these promising preliminary results in a larger cohort is currently on-going. TRIAL REGISTRATION: ClinicalTrials.gov NCT01691391. PMID- 27196138 TI - Rescuing Perishable Neuroanatomical Information from a Threatened Biodiversity Hotspot: Remote Field Methods for Brain Tissue Preservation Validated by Cytoarchitectonic Analysis, Immunohistochemistry, and X-Ray Microcomputed Tomography. AB - Biodiversity hotspots, which harbor more endemic species than elsewhere on Earth, are increasingly threatened. There is a need to accelerate collection efforts in these regions before threatened or endangered species become extinct. The diverse geographical, ecological, genetic, morphological, and behavioral data generated from the on-site collection of an individual specimen are useful for many scientific purposes. However, traditional methods for specimen preparation in the field do not permit researchers to retrieve neuroanatomical data, disregarding potentially useful data for increasing our understanding of brain diversity. These data have helped clarify brain evolution, deciphered relationships between structure and function, and revealed constraints and selective pressures that provide context about the evolution of complex behavior. Here, we report our field-testing of two commonly used laboratory-based techniques for brain preservation while on a collecting expedition in the Congo Basin and Albertine Rift, two poorly known regions associated with the Eastern Afromontane biodiversity hotspot. First, we found that transcardial perfusion fixation and long-term brain storage, conducted in remote field conditions with no access to cold storage laboratory equipment, had no observable impact on cytoarchitectural features of lizard brain tissue when compared to lizard brain tissue processed under laboratory conditions. Second, field-perfused brain tissue subjected to prolonged post-fixation remained readily compatible with subsequent immunohistochemical detection of neural antigens, with immunostaining that was comparable to that of laboratory-perfused brain tissue. Third, immersion-fixation of lizard brains, prepared under identical environmental conditions, was readily compatible with subsequent iodine-enhanced X-ray microcomputed tomography, which facilitated the non-destructive imaging of the intact brain within its skull. In summary, we have validated multiple approaches to preserving intact lizard brains in remote field conditions with limited access to supplies and a high degree of environmental exposure. This protocol should serve as a malleable framework for researchers attempting to rescue perishable and irreplaceable morphological and molecular data from regions of disappearing biodiversity. Our approach can be harnessed to extend the numbers of species being actively studied by the neuroscience community, by reducing some of the difficulty associated with acquiring brains of animal species that are not readily available in captivity. PMID- 27196142 TI - Neighborhood disadvantage, individual-level socioeconomic position and physical function: A cross-sectional multilevel analysis. AB - INTRODUCTION: Understanding associations between physical function and neighborhood disadvantage may provide insights into which interventions might best contribute to reducing socioeconomic inequalities in health. This study examines associations between neighborhood-disadvantage, individual-level socioeconomic position (SEP) and physical function from a multilevel perspective. METHODS: Data were obtained from the HABITAT multilevel longitudinal (2007-13) study of middle-aged adults, using data from the fourth wave (2013). This investigation included 6004 residents (age 46-71years) of 535 neighborhoods in Brisbane, Australia. Physical function was measured using the PF-10 (0-100), with higher scores indicating better function. The data were analyzed using multilevel linear regression and were extended to test for cross-level interactions by including interaction terms for different combinations of SEP (education, occupation, household income) and neighborhood disadvantage on physical function. RESULTS: Residents of the most disadvantaged neighborhoods reported significantly lower physical function (men: beta -11.36 95% CI -13.74, -8.99; women: beta 11.41 95% CI -13.60, -9.22). These associations remained after adjustment for individual-level SEP. Individuals with no post-school education, those permanently unable to work, and members of the lowest household income had significantly poorer physical function. Cross-level interactions suggested that the relationship between household income and physical function is different across levels of neighborhood disadvantage for men; and for education and occupation for women. CONCLUSION: Living in a disadvantaged neighborhood was negatively associated with physical function after adjustment for individual level SEP. These results may assist in the development of policy-relevant targeted interventions to delay the rate of physical function decline at a community-level. PMID- 27196141 TI - A behavioral economic perspective on smoking persistence in serious mental illness. AB - Serious mental illness (SMI) is associated with disproportionately high rates of cigarette smoking. The identification of factors that contribute to persistent smoking in people with SMI may lead to the development and adoption of tobacco control policies and treatment approaches that help these smokers quit. This commentary examines factors underlying smoking persistence in people with SMI from the perspective of behavioral economics, a discipline that applies economic principles to understanding drug abuse and dependence. Studies, conducted in the Northeastern US within the past 30years, that compare the reinforcing effects of nicotine and the costs of smoking in smokers with and without schizophrenia and depression are discussed, and interventions that may reduce the reinforcing efficacy of nicotine and increase the costs of smoking in people with SMI are described. PMID- 27196145 TI - Association of childhood and teen school performance and obesity in young adulthood in the US National Longitudinal Survey of Youth. AB - BACKGROUND: The literature suggests an association between poor school performance and obesity. However, little is known about academic achievement and behavior as possible risk factors for future obesity. METHOD: The analysis was based on data from 3172 participants aged 6 to 25years from the US National Longitudinal Survey conducted 1986 to 2010. Academic achievement, behavior problems and body mass index (BMI) were assessed at childhood (6-9) and teenhood (10-14). Height and weight were self-reported at pre-young adulthood (15-18) and young adulthood (19-25). RESULTS: Based on logistic regression stratified by sex and race/ethnicity, academic and behavioral deficiencies during childhood and teenhood were risk factors for young adult obesity with some sex and ethnic/racial differences. The highest prevalence rates of obesity by race/ethnicity and sex are as follows: black/Hispanic females, those in the lowest quartile of teen reading and math (32.8%); black/Hispanic males, those in lowest quartile of teen reading (26.1%); white males, those in the highest quartile of behavioral problems (21.9%); and white females, those in the lowest quartile teen math (23.2%). CONCLUSION: Poor school performance in childhood and teenhood is associated with an increased risk of adult obesity. Prospective studies should further examine the association of school performance and adult obesity and whether programs directed at improving school performance may have secondary gains in preventing obesity. PMID- 27196144 TI - Relationships of nativity and length of residence in the U.S. with favorable cardiovascular health among Hispanics/Latinos: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL). AB - Individuals with favorable levels of all readily measured major CVD risk factors (low CV risk) during middle age incur lower cardiovascular morbidity and mortality, lower all-cause mortality, and lower Medicare costs at older ages compared to adults with one or more unfavorable CVD risk factors. Studies on predictors of low CV risk in Hispanics/Latinos have focused solely on Mexican Americans. The objective of this study was to use data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL; enrolled 2008 to 2011) to assess relationships of nativity and length of residence in the US, a commonly used proxy for acculturation, with low CV risk (not currently smoking; no diabetes; untreated total cholesterol <200mg/dL; untreated blood pressure<120/<80; body mass index <25kg/m(2); and no major ECG abnormalities) in 15,047 Central American, South American, Cuban, Dominican, Mexican, Puerto Rican men and women, and Hispanic/Latino men and women identifying as other or >1 heritage. We also tested whether associations varied by Hispanic/Latino background. Women living in the US<10years were 1.96 (95% confidence interval: 1.37, 2.80) times more likely to be low CV risk than US-born women after adjusting for sociodemographic characteristics, diet, physical activity, and self reported experiences of ethnic discrimination. Findings varied in men by Hispanic/Latino background, but length of residence was largely unrelated to low CV risk. These findings highlight the role acculturative processes play in shaping cardiovascular health in Hispanics/Latinos. PMID- 27196143 TI - A review of epidemiologic research on smoking behavior among persons with alcohol and illicit substance use disorders. AB - Persons with alcohol use disorders (AUDs) and substance use disorders (SUDs) appear to be heavily affected by cigarette smoking. In order to address the consequences of smoking in this population, an understanding of the current state of knowledge is needed. Epidemiologic research provides the opportunity to obtain detailed information on smoking behaviors in large community samples. The aim of this paper was to synthesize the epidemiologic evidence on smoking among persons with AUDs/SUDs and suggest directions for future research. Literature searches of Medline and PubMed were used to identify articles and additional articles were elicited from publication reference lists. To be included in the review, papers had to be published in English, analyze epidemiologic data, and examine an aspect of smoking behavior in persons with AUDs/SUDs. Twenty-nine studies met inclusion criteria and were included in the review. In summary, epidemiologic evidence to date suggests greater lifetime and current smoking, nicotine dependence, and non cigarette tobacco use; lower quitting; and differences in quit attempts and withdrawal symptoms for persons with AUDs/SUDs compared to other people. Most studies examined nationally representative data and were conducted on persons in the United States and Australia. Few publications examined outcomes by demographics (e.g., gender, age) but these studies suggested that specific patterns differ by demographic subgroups. More research is needed on persons with AUDs/SUDs in order to develop the most effective public health and clinical interventions to reduce smoking behaviors, improve cessation outcomes, and reduce the harmful consequences of smoking for those with AUDs/SUDs. PMID- 27196146 TI - Prevalence and trends in physical activity among older adults in the United States: A comparison across three national surveys. AB - This paper examined how many older adults (65+years) are meeting physical activity (PA) Guidelines (PAG; 150min/week of moderate-to-vigorous PA) using data from three leading national surveys (NHANES, BRFSS and NHIS). The proportion of individuals meeting aerobic PAG was determined for the most recent cycle available for each survey (NHANES 2011-12, NHIS and BRFSS 2013). We also assessed whether PAG adherence has changed over time. Predicted margins from multinomial logistic regression were computed after adjusting for age, race/ethnicity and gender and sample weights. The proportion of older adults meeting PAG was 27.3% for NHANES, 35.8% for NHIS and 44.3% for BRFSS. Across all surveys, men reported higher levels of activity than women, Non-Hispanic whites reported higher levels than Non-Hispanic blacks and Hispanics, activity declined with age and was lower in those with functional limitations, all P<0.05. The proportion of older adults meeting PAG in the NHIS survey, the only survey where PA questions remained the same over time, increased from 25.7% in 1998 to 35.8% in 2013 (P<0.01). Point estimates for activity levels are different between surveys but they consistently identify sub-groups who are less active. Although older adults are reporting more activity over time, adherence to aerobic and strength training PAG remains low in this population and there is a need for effective interventions to prevent age related declines in PA and address health disparities among older adults. PMID- 27196147 TI - Trends and disparities in the prevalence of physicians' counseling on diet and nutrition among the U.S. adult population, 2000-2011. AB - BACKGROUND: Although healthy eating plays a crucial role in addressing the obesity and chronic disease epidemics, a few Americans have diets that meet dietary guidelines. Because physicians-delivered counseling is a strong predictor for behavioral modification among patients, the Healthy People Objectives have emphasized diet counseling since 2000. However, research on impact of physicians' counseling over time on a national level has been limited. METHODS: We used data from the 2000 and 2011 National Health Interview Surveys to apply a logistic regression model to identify predictors of physicians' counseling and examine any changes in disparities over a decade. RESULTS: In 2000, only 23.7% of our national sample had received dietary counseling, it increased to 32.6% in 2011. Hispanics were less likely than Whites to receive advice on diet in 2000 (adjusted odds ratio [AOR]=0.74, 95% confidence interval [CI]=0.62-0.88). By 2011, Hispanics 18% (AOR=1.18, CI=1.09-1.28) and Blacks were 42% (AOR=1.42, CI=1.32-1.54) more likely to receive advice from their physicians on diet than Whites. In both years, men were significantly less likely than women to receive counseling. The uninsured patients were increasingly less likely than insured patients in receiving diet counseling, being 60% less likely in 2011 (AOR=0.40, CI=0.37-0.40). Obese patients were substantially (88% in 2000 to 290% in 2011) more likely to receive counseling than normal-weight patients. CONCLUSIONS: The overall prevalence of physicians' counseling on diet increased moderately between 2000 and 2011. However, substantial disparities in dietary counseling related to access to care and gender continue to exist. PMID- 27196149 TI - Sporadic occurrence of non-diagnosed IgG4-related disease in lymphoma patients with a previous Sjogren's syndrome diagnosis. AB - BACKGROUND: IgG4-related disease (IgG4-RD) is a recently recognized fibro inflammatory disorder, which may affect many organs, and often comes to clinical attention due to tumor-like organ swelling or is identified incidentally by specific biopsy findings. Typical histopathology of IgG4-RD is lymphoplasmacytic infiltration rich in IgG4 + plasma cells (PCs), storiform fibrosis, and obliterative phlebitis. Patients with sicca symptoms can be misdiagnosed as primary Sjogren's syndrome (pSS) instead of IgG4-RD because of clinical and histopathological similarities. Moreover, an association with lymphoma development is described in both diseases. This study investigated signs of IgG4 RD in a population-based cohort of patients diagnosed with pSS complicated by lymphoma. METHODS: Patients with pSS and lymphoma diagnoses and available lymphoma specimens were identified by linkage with the Swedish Patient Register 1964-2007 and the Cancer Register 1990-2007 (n = 79). Clinical data and lymphomas were reviewed and the diagnoses evaluated. All lymphoma tissues and available minor salivary gland biopsies (n = 11) were immunostained for IgG4 + PCs and evaluated for other histopathological signs of IgG4-RD. In a case with specific findings of IgG4-RD, other available tissue specimens of the same patient were investigated for IgG4-RD. RESULTS: Only one patient of 79 (1.3%) had >10 IgG4 + PCs/high power field (HPF) in the lymphoma tissue, an unspecified low-grade B cell lymphoma localized in the submandibular gland. This patient also had other histopathological features of IgG4-RD in the lymphoma and a surgical lung biopsy taken five years before lymphoma diagnosis and, therefore, fulfilled the criteria for IgG4-RD. Occasional IgG4 + PCs (<10/HPF) without signs of IgG4-RD were observed in another six lymphomas. No IgG4 + PCs were identified in the minor salivary gland biopsies. CONCLUSION: Histopathological findings of IgG4-RD may co exist with low malignant B-cell lymphoma in patients with initially suspected pSS and may be associated with an underlying IgG4-RD. PMID- 27196148 TI - Home-based lifestyle intervention for rural adults improves metabolic syndrome parameters and cardiovascular risk factors: A randomised controlled trial. AB - The presence of metabolic syndrome (MetS) increases the risk of developing type 2 diabetes and cardiovascular disease. Targeted interventions to reduce MetS for high risk populations are crucial for the prevention of these chronic diseases. This study evaluated the effectiveness of a 6-month home-based physical activity and diet intervention for rural adults with, or at risk of MetS. The randomised controlled trial was conducted in Albany and surrounding towns, Western Australia, 2014-2015. Participants were screened for MetS using the International Diabetes Federation criteria, and eligible participants were randomly assigned to the intervention (n=201) or control (n=200) group. The intervention group received printed and online programme materials and motivational support, and the control group was waitlisted to receive the programme after post-test data collection. Anthropometry, lipid profiles, glycaemic status, and blood pressure were measured at baseline and 6-months post-test. In total, 312 (77.8%) participants completed post-test data collection and were included in the anthropometric analysis, and 274 (68.3%) participants were included in the blood sample analysis. After controlling for confounders, the intervention group significantly improved their triglyceride (-0.10mM, p=0.002), total cholesterol ( 0.09mM, p=0.02), and non-HDL cholesterol (-0.08mM, p=0.02) concentrations compared to the control group. Waist circumference (-2.11cm, p=0.03), waist-to hip ratio (-0.01, p=0.04), weight (-0.70kg, p=0.01), and body mass index ( 0.20kg/m(2), p<0.001) were also improved. These findings suggest that comprehensive home-based prevention programmes that include a combination of dietary and physical activity interventions are a promising means to prevent the onset of chronic disease in rural adults. TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12614000512628. PMID- 27196252 TI - Predicting Mortality in Low-Income Country ICUs: The Rwanda Mortality Probability Model (R-MPM). AB - INTRODUCTION: Intensive Care Unit (ICU) risk prediction models are used to compare outcomes for quality improvement initiatives, benchmarking, and research. While such models provide robust tools in high-income countries, an ICU risk prediction model has not been validated in a low-income country where ICU population characteristics are different from those in high-income countries, and where laboratory-based patient data are often unavailable. We sought to validate the Mortality Probability Admission Model, version III (MPM0-III) in two public ICUs in Rwanda and to develop a new Rwanda Mortality Probability Model (R-MPM) for use in low-income countries. METHODS: We prospectively collected data on all adult patients admitted to Rwanda's two public ICUs between August 19, 2013 and October 6, 2014. We described demographic and presenting characteristics and outcomes. We assessed the discrimination and calibration of the MPM0-III model. Using stepwise selection, we developed a new logistic model for risk prediction, the R-MPM, and used bootstrapping techniques to test for optimism in the model. RESULTS: Among 427 consecutive adults, the median age was 34 (IQR 25-47) years and mortality was 48.7%. Mechanical ventilation was initiated for 85.3%, and 41.9% received vasopressors. The MPM0-III predicted mortality with area under the receiver operating characteristic curve of 0.72 and Hosmer-Lemeshow chi-square statistic p = 0.024. We developed a new model using five variables: age, suspected or confirmed infection within 24 hours of ICU admission, hypotension or shock as a reason for ICU admission, Glasgow Coma Scale score at ICU admission, and heart rate at ICU admission. Using these five variables, the R-MPM predicted outcomes with area under the ROC curve of 0.81 with 95% confidence interval of (0.77, 0.86), and Hosmer-Lemeshow chi-square statistic p = 0.154. CONCLUSIONS: The MPM0-III has modest ability to predict mortality in a population of Rwandan ICU patients. The R-MPM is an alternative risk prediction model with fewer variables and better predictive power. If validated in other critically ill patients in a broad range of settings, the model has the potential to improve the reliability of comparisons used for critical care research and quality improvement initiatives in low-income countries. PMID- 27196253 TI - Facile and ultrasensitive fluorescence sensor platform for tumor invasive biomaker beta-glucuronidase detection and inhibitor evaluation with carbon quantum dots based on inner-filter effect. AB - Early detection and diagnosis have great practical significances for the effective prevention and treatment of cancer. In this study, we developed a novel, facile and ultra-sensitive fluorescence assay for the determination of tumor invasive biomarker beta-glucuronidase (GLU) based on the inner-filter effect (IFE). The nitrogen-doped carbon quantum dots (N-CQDs) with green photoluminescence were employed as the fluorophore in IFE, and 4-nitrophenyl-beta D-glucuronide (PNPG) was used to act as GLU substrate, and GLU catalytic product (p-nitrophenol (PNP)) was capable of acting as the robust absorber in IFE to turn off the fluorescence of N-CQDs due to the complementary overlap between the absorption of PNP and the excitation of N-CQDs. Thus, signal of GLU activity could be recorded by the fluorescence intensity of N-CQDs. Unlike other fluorescence sensing mechanism such as fluorescence resonance energy transfer (FRET) or photoinduced electron transfer (PET), IFE has no requirement for electron or energy transfer process or any chemical modification of fluorophore, which makes our assay more flexible and simple. The proposed method exhibited a good linear relationship from 1UL(-1) to 60UL(-1) (R(2)=0.9967) with a low detection limit of 0.3UL(-1). This method was also successfully applied to the analysis of serum samples and the inhibitor screening from natural product. The developed sensor platform was proven to be reliable, facile, sensitive, and selective, making it promising as a candidate for GLU activity detection in clinic tumor diagnose and anti-tumor drug screening. PMID- 27196255 TI - Molecularly imprinted nanohybrids based on dopamine-modified poly(gamma-glutamic acid) for electrochemical sensing of melamine. AB - A voltammetric sensor for melamine (MEL) was prepared from molecularly imprinted nanohybrids (MINBs). A dopamine modified poly-gamma-glutamic acid copolymer (gamma-PGA-DA) and MEL were self-assembled into MEL/gamma-PGA-DA nanoparticles (NPs) in aqueous solution via weak interactions, followed by adding an aqueous AgNO3 solution into the mixture. The Ag(+) was adsorbed in the MEL/gamma-PGA-DA NPs and spontaneously reduced to Ag NPs by the dopamine moieties of gamma-PGA-DA, forming Ag/MEL/gamma-PGA-DA MINBs, which were then cast on a gold electrode to form a MINBs film. The MEL was removed by electrolysis via catalysis of Ag NPs at a constant potential of 1.4V in phosphate buffer saline solution, to obtain a voltammetric sensor for MEL. The sensor responded linearly to MEL in the concentration range of 5*10(-18) to 5*10(-7)molL(-1). Compared to other published molecularly imprinted polymer sensors for sensing MEL, the prepared MINBs sensor had much wider detection range with lower detection limit. PMID- 27196254 TI - Silicon nanowire based biosensing platform for electrochemical sensing of Mebendazole drug activity on breast cancer cells. AB - Electrochemical approaches have played crucial roles in bio sensing because of their Potential in achieving sensitive, specific and low-cost detection of biomolecules and other bio evidences. Engineering the electrochemical sensing interface with nanomaterials tends to new generations of label-free biosensors with improved performances in terms of sensitive area and response signals. Here we applied Silicon Nanowire (SiNW) array electrodes (in an integrated architecture of working, counter and reference electrodes) grown by low pressure chemical vapor deposition (LPCVD) system with VLS procedure to electrochemically diagnose the presence of breast cancer cells as well as their response to anticancer drugs. Mebendazole (MBZ), has been used as antitubulin drug. It perturbs the anodic/cathodic response of the cell covered biosensor by releasing Cytochrome C in cytoplasm. Reduction of cytochrome C would change the ionic state of the cells monitored by SiNW biosensor. By applying well direct bioelectrical contacts with cancer cells, SiNWs can detect minor signal transduction and bio recognition events, resulting in precise biosensing. Our device detected the trace of MBZ drugs (with the concentration of 2nM) on electrochemical activity MCF-7 cells. Also, experimented biological analysis such as confocal and Flowcytometry assays confirmed the electrochemical results. PMID- 27196256 TI - Polyaniline-graphene based alpha-amylase biosensor with a linear dynamic range in excess of 6 orders of magnitude. AB - alpha-amylase is an established marker for diagnosis of pancreatic and salivary disease, and recent research has seen a substantial expansion of its use in therapeutic and diagnostic applications for infection, cancer and wound healing. The lack of bedside monitoring devices for alpha-amylase detection has hitherto restricted the clinical progress of such applications. We have developed a highly sensitive alpha-amylase immunosensor platform, produced via in situ electropolymerization of aniline onto a screen-printed graphene support (SPE). Covalently binding an alpha-amylase specific antibody to a polyaniline (PANI) layer and controlling device assembly using electrochemical impedance spectroscopy (EIS), we have achieved a highly linear response against alpha amylase concentration. Each stage of the assembly was characterized using a suite of high-resolution topographical, chemical and mechanical techniques. Quantitative, highly sensitive detection was demonstrated using an artificially spiked human blood plasma samples. The device has a remarkably wide limit of quantification (0.025-1000IU/L) compared to alpha-amylase assays in current clinical use. With potential for simple scale up to volume manufacturing though standard semiconductor production techniques and subsequently clinical application, this biosensor will enable clinical benefit through early disease detection, and better informed administration of correct therapeutic dose of drugs used to treat alpha-amylase related diseases. PMID- 27196257 TI - The Significance of Isolated Reactive Treponemal Enzyme Immunoassay in the Diagnosis of Early Syphilis. AB - BACKGROUND: The Treponemal test algorithm for syphilis screening is widely used. A diagnostic challenge between identifying early syphilis versus a false positive signal occurs in cases where the treponemal enzyme immunoassay (EIA) is reactive and confirmatory T. pallidum particle agglutination assay is negative. We investigated the diagnostic outcome of isolated reactive EIA in patients attending a sexual health clinic. METHODS: Results of syphilis serology tests carried out at Birmingham Whittall Street Clinic between August 10, 2010, and November 31, 2014, were reviewed. Cases with isolated EIA were routinely invited for repeat syphilis serology. Outcomes of patients with isolated EIA were reviewed and the proportion with confirmed positive syphilis serology on their repeat test identified. The number of isolated EIA cases needed to retest to identify 1 case of early syphilis was calculated. RESULTS: A total of 121,724 syphilis screening tests were performed. Among the 1561 individual patients with reactive EIA sera, 316 (20% of total reactive tests) had isolated reactive EIA. Repeat syphilis serology results of 163 patients were reviewed; 106 patients remained with isolated reactive EIA, 50 had negative EIA test and 7 (4.3%) had confirmed reactive EIA. Of the 7 patients, 2 had evidence of early syphilis infection. The number of isolated EIA needed to retest to identify 1 case of early syphilis was 81.5 (95% confidence interval, 22.9-671.4). CONCLUSIONS: Routine recall of patients with isolated EIA sera is not warranted. Risk of acquisition or presence of early syphilis should be assessed independently and irrespective of a negative syphilis screening test or isolated EIA. PMID- 27196259 TI - Comparison of Workflow, Maintenance, and Consumables in the GeneXpert Infinity 80 and Panther Instruments While Testing for Chlamydia trachomatis and Neisseria gonorrhoeae. AB - BACKGROUND: The 2015 Sexually Transmitted Diseases Treatment Guidelines from the Centers for Disease Control and Prevention recommend testing for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) using nucleic acid amplification tests, and prompt treatment of infected persons on site under direct observation. Faster time to results may enable treatment and management outcomes. METHODS: Workflow parameters for processing 1, 10, 48, 96, and 192 tests were determined in the GeneXpert Infinity 80 (Cepheid) and Panther (Hologic) instruments. RESULTS: In an Xpert CT/NG cartridge, the time to first results on the Infinity 80 was 1 hour 30 minutes for single or multiple tests and final results for 10, 48, 96, and 192 tests were available at 1 hour 37 minutes, 1 hour 54 minutes, 3 hour 17 minutes, and 5 hour 7 minutes, respectively. With the Aptima CT/GC assay on the Panther, the respective times were 3 hr 45 min for the first test result, and 3 hour 51 minutes, 4 hour 38 minutes, 5 hour 26 minutes, and 7 hour 4 minutes to final results. The Panther required more time for maintenance and consumed a greater variety of plastics and reagents but required less hands-on time when testing larger numbers of specimens. CONCLUSIONS: The Infinity 80 is a versatile instrument for continuous random access testing of small or large numbers of clinical specimens and may provide diagnostic results, in some settings, in time for treatment of CT and NG infections. PMID- 27196258 TI - Rapid Diagnosis of Trichomonas vaginalis by Testing Vaginal Swabs in an Isothermal Helicase-Dependent AmpliVue Assay. AB - BACKGROUND: The AmpliVue Trichomonas Assay (Quidel) is a new Federal Drug Administration-cleared rapid test for qualitative detection of Trichomonas vaginalis (TV) DNA in female vaginal specimens. The assay is based on BioHelix's helicase-dependent amplification isothermal technology in conjunction with a disposable lateral-flow detection device, with a total turnaround time of approximately 45 minutes. OBJECTIVE: The objective of this study was to compare the performance of this new assay to wet preparation and culture as well as to another Federal Drug Administration-cleared nucleic acid amplification assay. METHODS: Four clinician collected vaginal swabs were obtained from women attending sexually transmitted disease, family planning, and OB/GYN clinics and tested by AmpliVue Trichomonas Assay and comparator tests: saline microscopy, TV culture (InPouch), and Aptima TV. AmpliVue Trichomonas Assay results were compared with a composite positive comparator (CPC) as determined by the results from culture and/or wet mount microscopic examination. At least one of either the wet preparation or culture reference test results was required to be positive to establish CPC. RESULTS: A total of 992 patients, 342 symptomatic and 650 asymptomatic patients, were included in the study. Results for AmpliVue for all women combined compared with saline microscopy and culture as a CPC yielded a sensitivity of 100%. Specificity for all women was 98.2%. Overall percent agreement versus Aptima TV was 97.8%. Sensitivity for AmpliVue compared with Aptima was 90.7% %, whereas specificity was 98.9%. CONCLUSIONS: The rapid AmpliVue Trichomonas Assay performed as well as microscopy and culture, and had comparable sensitivity and specificity to another nucleic acid amplification test for the detection of TV. This study provided evidence of new diagnostic options and indicated very good performance of amplified testing for detection of TV in symptomatic and asymptomatic women. PMID- 27196260 TI - Population-Based Study of Prediagnostic Antibodies to Chlamydia trachomatis in Relation to Adverse Pregnancy Outcome. AB - BACKGROUND: Chlamydia trachomatis infection is one of the most common sexually transmitted reported bacterial infections worldwide. The well-known sequelae of chlamydial infection include pelvic inflammatory disease and tubal factor infertility, but the evidence linking C. trachomatis infection and adverse pregnancy outcome is inconsistent and has been largely based on case-control studies with limited study populations. We evaluated this link in a population based longitudinal biobank health registry setting. METHODS: The association between C. trachomatis major outer membrane protein (MOMP) peptide-specific IgG antibodies and ectopic pregnancy, miscarriage, and preterm delivery was examined in a prospective case-control study nested in the Finnish Maternity Cohort. Ectopic pregnancy and miscarriage cases were identified through the Hospital Discharge Register 1998-2005; cases with preterm deliveries were identified through the Finnish Medical Birth register 1988-2005. Control samples were retrieved from the Finnish Maternity Cohort serum bank. A total of 800 cases of ectopic pregnancy, 800 cases of miscarriage, and 1350 cases of preterm birth were included. Equal number of pregnant women without the outcome diagnosis served as controls. The cases and controls were matched by sampling time, at the serum sampling and postal code district. RESULTS: Antichlamydial IgG antibodies were associated with ectopic pregnancy. Positive antibody levels were found in 21.0% of cases and 14.6% of controls (P = 0.001; odds ratio, 1.56; 95% confidence interval, 1.20-2.03). Previous exposure to C. trachomatis, as indicated by serum antibodies, doubled the risk of ectopic pregnancy within age and was highest among women 35 years or older. Antichlamydial IgG antibody rates between the cases with miscarriage (16.3% in cases vs. 16.8% in controls) or preterm delivery (18.1% vs. 18.1%) and controls did not differ. CONCLUSIONS: Our findings confirm the association between previous exposure to C. trachomatis and ectopic pregnancy. We found no association between C. trachomatis seropositivity and miscarriage or preterm birth. PMID- 27196261 TI - Community-Based Assessment to Inform a Chlamydia Screening Program for Women in a Rural American Indian Community. AB - BACKGROUND: Rates of chlamydial infection in American Indian/Alaska Native women in the United States are approximately 4-fold those in non-Hispanic white women. We conducted a community-based survey of self-identified American Indian/Alaska Native women 14 to 25 years of age on a reservation in the Northwestern United States to inform a chlamydia screening strategy. METHODS: The anonymous survey assessed respondents' knowledge, perceptions, and preferences related to chlamydia screening, results receipt, and partner notification. We recruited women using respondent-driven sampling, school-based sampling, and direct recruitment through social media and fliers. Participants in schools completed the survey as a paper-based, self-administered survey. Other participants could complete the survey in person, by phone as an interviewer-administered survey, or online. RESULTS: We recruited 162 participants, most in schools (n = 83; 51%) or by peer referral (n = 55; 34%). Only 1 woman completed the survey online. Thirty one respondents (19%) reported a history of an unplanned first pregnancy, and 19 (12%) reported a history of a diagnosed sexually transmitted disease. Most women (n = 98; 63%) recognized the potential impact of Chlamydia trachomatis on fertility. The preferred site for chlamydia screening was the Indian Health Service Clinic (n = 114; 70%), but 79 women (41%) would accept a C. trachomatis test at a nonclinical testing site. Of the 56 women (35%) who would accept home testing, most preferred to get the test kit from a clinic. CONCLUSIONS: Our results suggest that Indian Health Service efforts to increase chlamydia screening in the clinic and through outreach may be more successful than promotion of home testing in this population. PMID- 27196262 TI - Use of the Historical Limits Method to Detect Increases in Primary and Secondary Syphilis, Arizona 2011-2014: An Exploratory Study. AB - BACKGROUND: Increasing numbers of reported primary and secondary (P&S) syphilis cases in the United States suggest the need for improved surveillance methods. An outbreak detection method using reported syphilis test results, which can be counted before the conclusion of a syphilis case investigation, could lead to timelier outbreak detection. METHODS: The historical limits comparison method was used to compare the number of positive rapid plasma reagin results reported during 2011-2014 with data for the preceding 3 years. An outbreak alert was generated when the monthly count of positive rapid plasma reagin quantitative results was greater than the historical mean plus 2 standard deviations for 2 consecutive months. RESULTS: Three outbreak alerts occurred during 2011-2014. The first alert occurred in December 2012 in Maricopa County (Phoenix area). Primary and secondary cases subsequently increased from 10 in January 2013 to 15 in March followed by 5 months of consecutive increases. A second alert was generated for Maricopa County in May 2014. Primary and secondary cases increased from 29 in May to 42 in July 2014. Reported cases remained elevated for approximately 7 months after the second alert. In December 2013, an outbreak alert occurred for Pima County (Tucson area). The number of reported P&S syphilis cases in Pima County increased from 6 in February to 15 in March. Counts of reported cases remained elevated for approximately 6 months after the alert. CONCLUSIONS: Use of historical limits comparison method based on syphilis laboratory results can provide an outbreak alert before increases in reported cases of P&S syphilis. PMID- 27196263 TI - Current physico-biochemistry in steroid research and status of structural biology for steroid-converting enzymes. PMID- 27196265 TI - Early Discharge of Neutropenic Pediatric Oncology Patients Admitted With Fever. AB - BACKGROUND: Fever and neutropenia (FN) is a common complication of pediatric oncology therapy and accounts for a large number of hospital admissions. Standard therapy for FN includes hospital admission and empiric antibiotics. Strict adherence to this practice leads to prolonged hospitalizations that may be unnecessary for patients at low risk of having an underlying significant infection. PROCEDURE: Children admitted with FN could be discharged after a minimum of 48 hr with no further antibiotic therapy once they had been afebrile for 24 hr with negative blood cultures from initial presentation, regardless of their neutrophil count. We performed a retrospective review with regard to readmissions and subsequent documented infections in FN patients discharged with an ANC of <=500 cells/mm(3) . RESULTS: There were 299 FN admissions in 188 patients who were discharged prior to achieving an ANC of >=500 cells/mm(3) . Readmission to the hospital during the same period of neutropenia occurred in 50 cases (16.7%) with 27 infections diagnosed in 21 patients. Patients discharged with an ANC of <=100 cells/mm(3) (odds ratio 3.7) and patients with acute lymphoblastic leukemia (odds ratio 2.6) were more likely to be readmitted for fever. All patients that developed a significant infection had an ANC of <=100 cells/mm(3) at admission and discharge. In patients that developed a significant infection, only one required admission to the intensive care unit with no deaths. CONCLUSIONS: The practice of discharging patients with persistent neutropenia who are afebrile with negative blood cultures produces acceptable rates of readmission and subsequent infection and does not lead to increased morbidity and mortality. PMID- 27196264 TI - Correction: Virtual Electrophysiological Study of Atrial Fibrillation in Fibrotic Remodeling. AB - [This corrects the article DOI: 10.1371/journal.pone.0117110.]. PMID- 27196266 TI - The Status of Health Literacy Research in Health Communication and Opportunities for Future Scholarship. AB - While national concern is growing, the scholarly body of knowledge in health literacy is still relatively small in health communication literature. The field began to distinguish itself as an outgrowth of adult literacy that focused on patient understanding of health information. It grew out of medicine and public health science mostly, and still today the majority of research can be found in health professional journals. However, the links with health communication, particularly with provider-patient communication and with printed health information, have been established and documented over the last decade. This article is a conceptual review that highlights state-of-the-science literature that has made connections between health literacy and health communication. Evidence reveals the contribution that health literacy can have on the health communication body of knowledge. The article illuminates the gaps in research and possibilities for theory development and future studies. PMID- 27196268 TI - Offset layered closure reduces deep wound infection in early-onset scoliosis surgery. AB - Deep wound infection is a common complication in early-onset scoliosis (EOS) surgery. Soft tissue technique has received less attention as a means to reduce infection. A retrospective review of 1170 EOS surgeries (single surgeon, institution) investigated the impact of offset layered closure (OLC) and soft tissue awareness. The introduction of OLC reduced deep infection from 3.0% in 99 surgeries to 0.37% in 1071. Logistic regression confirmed that OLC led to significantly lower odds of infection (P=0.007). This deep infection rate (0.37%) is more typical of elective surgery, providing a more optimistic view of infection in EOS surgery than generally reported. PMID- 27196267 TI - The Protective Effects of Salubrinal on the Cartilage and Subchondral Bone of the Temporomandibular Joint under Various Compressive Mechanical Stimulations. AB - Excessive mechanical loads on the temporomandibular joint (TMJ) can cause mandibular cartilage degradation and subchondral bone erosion, but the treatment of these conditions remains challenging. Salubrinal, which target eukaryotic translation initiation factor 2 alpha, has been shown to have multiple beneficial effects on skeletal tissue. Here, we examined the effect of a Salubrinal injection on the mandibular cartilage and subchondral bone of the TMJ under various compressive stresses. We conducted in vivo analyses in rat models using various compressive stresses (40 g and 80 g), and we observed time-related degeneration and pathological changes in the cartilage and subchondral bone of the TMJ at days 1, 3 and 7 through histological measurements, subcellular observation, and changes in proliferation and apoptosis. After the Salubrinal injection, the thickness of the cartilage recovered, and the pathological change was alleviated. In the Salubrinal/light (Sal/light) compressive stress group, the drug altered the proliferation and apoptosis of chondrocytes most significantly at day 1. In the Salubrinal/heavy (Sal/heavy) compressive stress group, the drug increased the proliferation of chondrocytes most significantly at day 1 and reduced the apoptosis of chondrocytes most significantly at day 7. Salubrinal also increased the area of the bone trabeculae and suppressed inflammatory responses and pathological change in the subchondral bone of the TMJ. Together, these results indicate that the administration of Salubrinal reduces apoptosis and strengthens the proliferation of chondrocyte to varying degrees at days 1, 3 and 7 under various compressive mechanical stresses, both of which contribute to the recovery of cartilage thickness and the alleviation of pathological change. Salubrinal also suppresses inflammatory responses and pathological change in the subchondral bone of the TMJ. PMID- 27196269 TI - Delayed treatment of femoral neck fractures in 58 children: open reduction internal fixation versus closed reduction internal fixation. AB - The best treatment plan for femoral neck fractures in children in whom treatment is delayed by more than 24 h is unclear because of the limited number of such cases reported. This study compares the outcomes of closed and open reduction performed 24 h after the injury was sustained. We retrospectively reviewed 58 cases (40 males, 18 females) of femoral neck fractures reset after more than a 24 h delay at our hospital (May 2005 to May 2014). According to Delbet's classification, there were 30 type II fractures (51.7%), 21 type III fractures (36.2%), and seven type IV fractures (12.1%). A total of 21 patients underwent closed reduction and internal fixation; the remaining patients underwent open reduction and internal fixation. The follow-up period was 17-61 months (average, 35.1 months). The results were classified according to Ratliff's criteria. With the exception of one case of bone nonunion (closed reduction group), the fracture was healed in the remaining cases. The average healing time was 10.82 weeks (9-13 weeks). The incidence of avascular necrosis was significantly lower in the open reduction group. Further, the percentage of results classified as 'fine' according to Ratliff's criteria was significantly higher in the open reduction group than in the closed reduction group. Coxa vara occurred in three patients in the closed reduction group, but it did not occur in any of the patients in the open reduction group. The incidence of avascular necrosis was significantly lower in the patients who achieved anatomical reduction than in the patients who only achieved acceptable reduction. Finally, the results in the anatomical reduction group were obviously better than those in the acceptable reduction group. Open reduction with internal fixation yielded better outcomes than closed reduction in this group of children with displaced femoral neck fractures who were treated more than 24 h after the injury. This may be related to the better reduction quality in the open reduction group. LEVEL OF EVIDENCE: Therapeutic studies: investigating the results of treatment, Level III. PMID- 27196270 TI - Effects of surgical intervention on trochlear remodeling in pediatric patients with recurrent patella dislocation cases. AB - Patella instability is often encountered among physically active pediatric athletes, and surgical intervention is useful in cases with recurrent patella dislocations, chronic instability, and abnormal alignment. Several surgical procedures have been used for patella-realignment and stabilization, but the effects of surgical intervention on bony trochlear remodeling in skeletally immature patients have not been well studied. We thus present two cases of pediatric recurrent patella dislocations that showed trochlear remodeling following patella-realignment surgery. The first case describes an 11-year-old female treated with a Roux-Golthwait procedure and the second case highlights a 12-year-old male treated with lateral release and medial capsular reefing. The Merchant technique, a radiographic criterion that was designed to evaluate patella alignment in relation to the femoral trochlea groove, including sulcus and congruence angles was used to measure postoperative bony development. Both pediatric patients showed successful outcomes following surgical interventions for chronic patella instability. Using the Merchant technique, both patients showed improved congruence and sulcus angles postoperatively. Patella realignment in skeletally immature patients may be beneficial for promoting trochlear remodeling and deepening of the trochlear groove, which may help protect against future dislocation or subluxation events. LEVEL OF EVIDENCE: Level IV, case report. PMID- 27196271 TI - Diving into the rat plasma proteome to get to the bottom of decompression sickness. AB - Decompression sickness (DCS) is the collective term for an array of signs and symptoms triggered by ambient pressure reduction. It is of particular concern to divers as they decompress on ascend from depth to sea surface, but despite a long history of studies the determinants of DCS risk are incompletely understood and there are no validated biomarkers. In this issue of Proteomics Clinical Applications, Lautridou et al. [8] report on their search for DCS biomarkers in rats exposed to simulated diving. By comparing the plasma proteomes from animals showing neurological symptoms to those emerging from dives unaffected, they identified several high-abundance proteins not previously associated with DCS. The most significant finding was a near depletion of thyroxine- and vitamin A transporter transthyretin in symptomatic rats. In addition to their potential role as diagnostic biomarkers, the proteins identified in Lautridou's study may offer new pieces in the yet incomplete puzzle of DCS etiology. PMID- 27196288 TI - Reduced Height (Rht) Alleles Affect Wheat Grain Quality. AB - The effects of dwarfing alleles (reduced height, Rht) in near isogenic lines on wheat grain quality are characterised in field experiments and related to effects on crop height, grain yield and GA-sensitivity. Alleles included those that conferred GA-insensitivity (Rht-B1b, Rht-B1c, Rht-D1b, Rht-D1c) as well as those that retained GA-sensitivity (rht(tall), Rht8, Rht8 + Ppd-D1a, Rht12). Full characterisation was facilitated by including factors with which the effects of Rht alleles are known to interact for grain yield (i.e. system, [conventional or organic]; tillage intensity [plough-based, minimum or zero]; nitrogen fertilizer level [0-450 kg N/ha]; and genetic backgrounds varying in height [cvs Maris Huntsman, Maris Widgeon, and Mercia]. Allele effects on mean grain weight and grain specific weight were positively associated with final crop height: dwarfing reduced these quality criteria irrespective of crop management or GA-sensitivity. In all but two experiments the effects of dwarfing alleles on grain nitrogen and sulphur concentrations were closely and negatively related to effects on grain yield, e.g. a quadratic relationship between grain yield and crop height manipulated by the GA-insensitive alleles was mirrored by quadratic relationships for nitrogen and sulphur concentrations: the highest yields and most dilute concentrations occurred around 80cm. In one of the two exceptional experiments the GA-insensitive Rht-B1b and Rht-B1c significantly (P<0.05) reduced grain nitrogen concentration in the absence of an effect on yield, and in the remaining experiment the GA-sensitive Rht8 significantly reduced both grain yield and grain nitrogen concentration simultaneously. When Rht alleles diluted grain nitrogen concentration, N:S ratios and SDS-sedimentation volumes were often improved. Hagberg falling number (HFN) was negatively related to crop height but benefits from dwarfing were only seen for GA-insensitive alleles. For HFN, therefore, there was the strongest evidence for a direct pleiotropic effect of GA insensitivity, rather than an effect consequential to yield and/or height. PMID- 27196272 TI - The Challenges of Implementing Next Generation Sequencing Across a Large Healthcare System, and the Molecular Epidemiology and Antibiotic Susceptibilities of Carbapenemase-Producing Bacteria in the Healthcare System of the U.S. Department of Defense. AB - OBJECTIVE: We sought to: 1) provide an overview of the genomic epidemiology of an extensive collection of carbapenemase-producing bacteria (CPB) collected in the U.S. Department of Defense health system; 2) increase awareness of the public availability of the sequences, isolates, and customized antimicrobial resistance database of that system; and 3) illustrate challenges and offer mitigations for implementing next generation sequencing (NGS) across large health systems. DESIGN: Prospective surveillance and system-wide implementation of NGS. SETTING: 288-hospital healthcare network. METHODS: All phenotypically carbapenem resistant bacteria underwent CarbaNP(r) testing and PCR, followed by NGS. Commercial (Newbler and Geneious), on-line (ResFinder), and open-source software (Btrim, FLASh, Bowtie2, an Samtools) were used for assembly, SNP detection and clustering. Laboratory capacity, throughput, and response time were assessed. RESULTS: From 2009 through 2015, 27,000 multidrug-resistant Gram-negative isolates were submitted. 225 contained carbapenemase-encoding genes (most commonly blaKPC, blaNDM, and blaOXA23). These were found in 15 species from 146 inpatients in 19 facilities. Genetically related CPB were found in more than one hospital. Other clusters or outbreaks were not clonal and involved genetically related plasmids, while some involved several unrelated plasmids. Relatedness depended on the clustering algorithm used. Transmission patterns of plasmids and other mobile genetic elements could not be determined without ultra-long read, single-molecule real-time sequencing. 80% of carbapenem-resistant phenotypes retained susceptibility to aminoglycosides, and 70% retained susceptibility to fluoroquinolones. However, among the CPB-confirmed genotypes, fewer than 25% retained susceptibility to aminoglycosides or fluoroquinolones. CONCLUSION: Although NGS is increasingly acclaimed to revolutionize clinical practice, resource-constrained environments, large or geographically dispersed healthcare networks, and military or government-funded public health laboratories are likely to encounter constraints and challenges as they implement NGS across their health systems. These include lack of standardized definitions and quality control metrics, limitations of short-read sequencing, insufficient bandwidth, and the current limited availability of very expensive and scarcely available sequencing platforms. Possible solutions and mitigations are also proposed. PMID- 27196290 TI - Correction to: Childhood Obesity 2016;12(1):1-11. PMID- 27196289 TI - Prevalence and Characteristics of Interventional Trials Conducted Exclusively in Elderly Persons: A Cross-Sectional Analysis of Registered Clinical Trials. AB - BACKGROUND: Elderly patients represent the greatest consumers of healthcare per capita but have historically been underrepresented in clinical trials. It is unknown how many trials are designed to focus exclusively on elderly patients. OBJECTIVE: To define the prevalence of interventional trials that study exclusively elderly persons and describe the characteristics of these trials, including their distribution across conditions most prevalent in the elderly. DESIGN: All interventional clinical trials enrolling exclusively elderly patients (>=65 years), conducted primarily in high-income countries, and initiated between 2006 and 2014, identified through ClincialTrials.gov. MAIN MEASURES: Trials were identified and characterized according to design features and disease categories studied. Across disease categories we examined the burden of disease in the elderly in high-income countries (measured in disability-adjusted life years [DALYs]) and compared to the number of trials conducted exclusively in the elderly. RESULTS: Among 80,965 interventional trials, 1,112 (1.4%) focused on elderly patients. Diverse types of interventions were studied in these trials (medications 33%, behavioral interventions 18%, and dietary supplements 10%) and the majority was funded by non-profit organizations (81%). Studies tended to be small (median sample size 122 participants [IQR 58, 305]), single-center studies (67%). Only 43% of 126 disease categories affecting elderly persons were studied in trials focused on the elderly. Among these disease categories, there was a 5162-fold range in the ratio of DALYs per trial. Across 5 conditions where over 80% of DALYs are in the elderly, there were a total of only 117 trials done exclusively in the elderly. CONCLUSIONS: Very few and mostly small studies are conducted exclusively in elderly persons, even for conditions that affect almost exclusively the elderly. PMID- 27196291 TI - Correction to: AIDS Res Hum Retroviruses 2016;32;420-426. PMID- 27196292 TI - CP-25 attenuates the inflammatory response of fibroblast-like synoviocytes co cultured with BAFF-activated CD4(+) T cells. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Total glucosides of paeony (TGP) is the first anti-inflammatory immune regulatory drug approved for the treatment of rheumatoid arthritis in China. A novel compound, paeoniflorin-6'-O-benzene sulfonate (code CP-25), comes from the structural modification of paeoniflorin (Pae), which is the effective active ingredient of TGP. The aim of the present study is to investigate the effect of CP-25 on adjuvant arthritis (AA) fibroblast-like synoviocytes (FLS) co-cultured with BAFF-activated CD4(+) T cells and the expression of BAFF-R in CD4(+) T cells. METHODS: The mRNA expression of BAFF and its receptors was assessed by qPCR. The expression of BAFF receptors in CD4(+) T cells was analyzed by flow cytometry. The effect of CP-25 on AA rats was evaluated by their joint histopathology. The cell culture growth of thymocytes and FLS was detected by cell counting kit (CCK-8). The concentrations of IL 1beta, TNF-alpha, and IL-6 were measured by Enzyme-linked immunosorbent assay (ELISA). RESULTS: The mRNA expression levels of BAFF and BAFF-R were enhanced in the mesenteric lymph nodes of AA rats, TACI expression was reduced, and BCMA had no change. The expression of BAFF-R in CD4(+) T cells was also enhanced. CP-25 alleviated the joint histopathology and decreased the expression of BAFF-R in CD4(+) T cells from AA rats in vivo. In vitro, CP-25 inhibited the abnormal cell culture growth of BAFF-stimulated thymocytes and FLS. In the co-culture system, IL-1beta, IL-6 and TNF-alpha production was enhanced by FLS co-cultured with BAFF activated CD4(+) T cells. Moreover, BAFF-stimulated CD4(+) T cells promoted the cell culture growth of FLS. The addition of CP-25 decreased the expression of BAFF-R in CD4(+) T cells and inhibited the cell culture growth and cytokine secretion ability of FLS co-cultured with BAFF-activated CD4(+) T cells. CONCLUSION: The present study indicates that CP-25 may repress the cell culture growth and cytokine secretion ability of FLS, and its inhibitory effects might be associated with its ability to inhibit the expression of BAFF-R in CD4(+) T cells in a co-culture. These observations might provide a scientific basis for the development of new drugs for the treatment of autoimmune diseases by CP-25. PMID- 27196293 TI - Gastrointestinal safety and efficacy of long-term GCSB-5 use in patients with osteoarthritis: A 24-week, multicenter study. AB - ETHNOPHARMACOLOGY RELEVANCE: A previous study indicated non-inferiority of GCSB-5 to celecoxib regarding efficacy and safety in treating OA; however, the gastrointestinal (GI) safety data was limited to 12 weeks. Accordingly, a longer term study with a larger number of patients was necessary to establish the GI safety of GCSB-5. AIM OF STUDY: The primary goal was to determine the safety and efficacy of 24-week use of GCSB-5. The secondary goal was to compare the GI safety data of GCSB-5 with that of the previously reported Celecoxib Long-term Arthritis Safety Study (CLASS). METHOD: This was a 24-week, multicenter, single arm phase IV Study for the safety and efficacy of GCSB-5. A total of 761 patients were enrolled and 756 patients received at least one dose of GCSB-5. Among them, 629 patients (82.7%) completed the 24 week follow up. The primary goal was to determine the safety and efficacy of GCSB-5 for 24 weeks. The secondary goal was to compare the GI safety data of GCSB-5 with that of the previously reported Celecoxib Long-term Arthritis Safety Study (CLASS). RESULTS: The incidence of GI disorders of GCSB-5 was 23.7%. The annual rate of perforation, ulcer obstruction, or bleeding (PUB) incidence was 0.0%. The drop-out rate due to GI disorders following GCSB-5 use was 4.8%. Compared to celecoxib data from CLASS, the incidence of GI disorders (23.7% vs. 31.4%, p<0.001), annual rate of PUB and gastroduodenal ulcers (0.0% vs 2.2%, p=0.004), and drop-out rate due to GI disorders following GCSB-5 use were significantly low (4.8% vs 8.7%, p<0.001). Efficacy was proven by significant improvements in Western Ontario McMaster Questionnaire (WOMAC) scale, Korean Knee Score (KKS), 100-mm pain visual analogue scale (VAS), and physician's global assessments of patient's response to therapy (PGART). CONCLUSIONS: The safety and efficacy profile of GCSB-5 are comparable to celecoxib. These results indicate GCSB-5 is safe for a long-term treatment of knee OA patients. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01604239). PMID- 27196294 TI - Cis- and Trans-gnetin H from Paeonia suffruticosa suppress inhibitor kappa B kinase phosphorylation in LPS-stimulated human THP-1 cells. AB - ETHNOPHARMACOLOGICAL RELEVANCE: The inflammatory response is an important mechanism in host defense; however, overstimulation and chronic inflammation are involved in many important human diseases. Currently, tumor necrosis factor-alpha blockers such as infliximab and adalimumab along with methotrexate are used in cases of severe and chronic disease. However, there are severe side effects and limitations associated with these treatments. Cis- and trans-gnetin H are compounds isolated from the seeds of Paeonia suffruticosa, a medicinal plant used in traditional Chinese medicine for the treatment of many conditions, including inflammatory diseases. In this study, we investigated possible anti-inflammatory mechanisms of cis- and trans-gnetin H against LPS-stimulated human THP-1 cells. MATERIAL AND METHODS: PMA-differentiated THP-1 cells were pretreated with increasing concentrations of cis- and trans-gnetin H with or without LPS. Following treatment, cytotoxicity and the TNF-alpha, IL-1beta, and IL-8 response were measured. We also characterized the nuclear translocation of NF-kappaB subunit p65 (RelA) by immunofluorescence and then investigated NF-kappaB activation by measuring the phosphorylation of NF-kappaB mediators, IKK-beta, IkappaB alpha, and p65 by western blotting. RESULTS: We found that cis- and trans gnetin H significantly inhibited the cytokine response in a concentration dependent manner without affecting cell viability. Cis- and trans-gnetin H effectively inhibited nuclear translocation of p65 and phosphorylation of IKK beta, IkappaB alpha, and p65. While both compounds showed promising anti inflammatory effects, trans-gnetin H was determined to be more effective in suppressing cytokine responses. CONCLUSION: We demonstrated that cis- and trans gnetin H suppress cytokine response in LPS-stimulated THP-1 cells by preventing activation of key signaling molecules, IKK-beta, IkappaB alpha, and p65, involved in the NF-kappaB pathway and suggest the use of cis- and trans-gnetin H in potential therapies for conditions and diseases associated with chronic inflammation. PMID- 27196295 TI - Huangqi decoction alleviates dimethylnitrosamine-induced liver fibrosis: An analysis of bile acids metabolic mechanism. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Huangqi Decoction (HQD), a classical traditional Chinese medicine (TCM) formula, is used to treating liver injury in China. The aim of the study is to investigate mechanisms of HQD against dimethylnitrosamine (DMN)-induced liver fibrosis underlying metabolic profiles of bile acids. MATERIALS AND METHODS: DMN-induced liver fibrosis rats were administrated HQD and its compounds, astragalosides (AS), glycyrrhizic acid (GA) and their combination. The anti-fibrosis effects were evaluated and targeted metabolomics by UPLC-MS was used to examine whether HQD had an influence on bile acid metabolism. The levels of mRNAs associated with bile acid metabolism were expressed by RT-PCR. Chenodeoxycholic acid (CDCA)-induced hepatic stellate cells (HSCs) proliferation and activation were examined using MTS assay and Western blot. RESULTS: Histopathological changes and serum liver function in HQD group had significant improvements (P<0.01). Concentrations of free bile acids and taurine conjugates were significantly increased in DMN group (P<0.05). HQD and its compounds restored the increased bile acids to normal levels, and HQD was more effected on parts of bile acids. Furthermore, the levels of mRNAs related bile acid synthesis and reabsorption such as CYP7A1, CYP8B1, CYP27A1, OATP2, OATP3, OATP4 and NTCP were significantly down-regulated in DMN group (P<0.05), mRNAs related excretion such as MRP3 and BESP were up-regulated (P<0.01), and CYP7A1, CYP8B1, OATP3, OATP4, NTCP and MRP3 restored to normal levels by HQD treatment. Moreover, CDCA induced HSCs proliferation and activation were weaken by HQD (P<0.05) with down regulated alpha-SMA, TGF-beta1, p-Smad2 and p-Smad3 expressions. CONCLUSIONS: HQD alleviated DMN-induced liver fibrosis with a better effect than its compounds, which may be involved in the regulation of bile acid metabolism enzyme. Moreover, HQD may inhibit CDCA-induced HSCs proliferation and activation. PMID- 27196296 TI - Effects of Viola yedoensis Makino anti-itching compound on degranulation and cytokine generation in RBL-2H3 mast cells. AB - ETHNOPHARMACOLOGICAL RELEVANCE: The Chinese herb compound prescription Viola yedoensis Makino Anti-itching Compound (VYAC), which consists of Viola yedoensis Makino, herb, Sophora flavescens Aiton, root, and Dictamnus dasycarpus Turcz, root and rhizome, has been traditionally used to treat various skin allergic inflammatory diseases in clinic. AIM OF THE STUDY: The aim of this study is to investigate the effects of VYAC on degranulation and to determine its anti inflammatory mechanism in RBL-2H3 mast cells. MATERIALS AND METHODS: VYAC was extracted with water-coction extraction (Shufen et al., 2012). The aqueous extracts were concentrated in vacuum under reduced pressure and lyophilized using a freeze dryer, and lyophilized powder was obtained. MTT was used to evaluate the cytotoxic of VYAC on RBL-2H3 cells. Degranulation was carried out with RBL-2H3 cell model, which was stimulated with A23187 plus PMA. beta-Hexosaminidase and histamine were measured to evaluate degranulation. The mRNA levels of inflammation cytokines (IL-1beta, TNF-alpha, IL-6, and iNOS) were investigated by RT-PCR to explain the anti-inflammatory mechanism of VYAC. RESULTS: VYAC did not show cytotoxic effect on RBL-2H3 cells in the range of 25-400MUg/mL. A higher dose of VYAC (800MUg/mL) showed significant cytotoxicity (P<0.05). VYAC could significantly inhibit beta-hexosaminidase and histamine release when treated with 100, 200, and 400MUg/mL (P<0.05), but could not significantly inhibit beta Hexosaminidase and histamine release when treated with 25 and 50MUg/mL (p>0.05). The mRNA levels of inflammatory cytokines (TNF-alpha, IL-1beta, IL-6, and iNOS) could significantly decrease when treated with 200 and 400MUg/mL (P<0.05) of VYAC, which were associated with the development of inflammation. CONCLUSIONS: Results showed that VYAC inhibited beta-hexosaminidase and histamine release, which was inhibit A23187 plus PMA stimulated RBL-2H3 cell degranulation and downregulated inflammatory cytokines (IL-1beta, TNF-alpha, IL-6, and iNOS) expression to block inflammatory development. PMID- 27196297 TI - The estrogenic properties of Danggui Buxue Tang, a Chinese herbal decoction, are triggered predominantly by calycosin in MCF-7 cells. AB - BACKGROUND: Danggui Buxue Tang (DBT), a Chinese herbal decoction containing Astragali Radix (AR; roots of Astragalus memebranaceus (Fisch.) Bunge var. mongholicus (Bunge) Hsiao) and Angelicae Sinensis Radix (ASR; roots of Angelica sinensis Oliv.) at a weight ratio of 5:1, is used to improve menopausal syndromes in women. Several lines of evidence indicate that DBT has strong estrogenic property; however, the action mechanism of this herbal decoction is not known. Calycosin, a major flavonoid in AR, shares similar structure with beta-estradiol, and thus which is hypothesized to be the key compound of DBT in responsible for such estrogenic properties. AIMS: We aimed to determine the role of calycosin in DBT in terms of its estrogenic functions by the creation of calycosin-depleted DBT (DBTDeltacal) and calycosin-added DBT (DBT+cal) herbal extracts. METHODS: The signalings triggered by DBT?cal, DBT+cal, and parental DBT were compared in cultured MCF-7 cells by determining: (i) the activation of estrogen responsive element; (ii) the phosphorylation of estrogen receptor alpha (ERalpha); and (iii) the phosphorylation of Erk1/2. The DBT-induced responses were in dose- and/or time-dependent manners. RESULTS: The estrogenic signals triggered by DBT were markedly reduced in DBTDeltacal, and in contrast the addition of calycosin in DBT, i.e. DBT+cal, enhanced the responses by 2-5 folds; however, calycosin alone did not show such properties. In parallel, the DBT-induced responses could be significantly blocked by inhibitors for estrogen receptor and mitogen activated protein kinases. CONCLUSION: Thus, we hypothesize that calycosin is an indispensable chemical in DBT, and which plays a linker in orchestrating multi components of DBT as to achieve the maximal estrogenic functions. These discoveries should be invaluable in drug development and in investigating the modernization of traditional Chinese medicine from a new perspective. PMID- 27196298 TI - Lonicerae Japonicae Flos attenuates diabetic retinopathy by inhibiting retinal angiogenesis. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Lonicerae Japonicae Flos (Jin-Yin-Hua) is a well known traditional Chinese medicine used for clearing away heat and toxic material. AIM OF THE STUDY: This study aims to observe the attenuation of aqueous extract of Lonicerae Japonicae Flos (FL) against streptozotocin (STZ)-induced diabetic retinopathy (DR) and its engaged mechanism. MATERIALS AND METHODS: STZ induced proliferative DR (PDR) for 5 month in C57BL/6 mice was used in this study. Retinal vessels were observed by immunofluorescence staining with cluster of differentiation 31 (CD31) and histopathological evaluation. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum vascular endothelial growth factor (VEGF) content. Cell proliferation was detected by 3-(4, 5-dimethylthiazol 2-yl) 2, 5-diphenyltetrazolium bromide (MTT) assay in choroid-retinal endothelial RF/6A cells. VEGF-induced tube formation in RF/6A cells was observed. The contents of chlorogenic acid (CGA), caffeic acid (CA), and luteolin in FL were detected by high-performance liquid chromatography (HPLC). RESULTS: Histopathological evaluation demonstrated that retinal vessels were increased in STZ-induced PDR mice, whereas FL decreased such increase. The results of CD31 staining also showed that FL decreased the increased number of retinal vessels in STZ-induced PDR mice. In addition, FL reduced the increased serum VEGF content in STZ-induced PDR mice. FL reduced VEGF-induced RF/6A cell proliferation in the concentration-dependent manner, but had no obvious effect on RF/6A cell viability without VEGF stimulation. VEGF-induced tube formation in RF/6A cells was inhibited by different concentrations of FL. CGA, CA and luteolin all inhibited VEGF-induced tube formation in RF/6A cells, and the lowest effective concentration of CGA and CA was both 0.625MUM, but of luteolin was 5MUM. Furthermore, the results of HPLC demonstrated that the amount of CGA was the highest in FL. CONCLUSIONS: FL ameliorates STZ-induced PDR by inhibiting retinal angiogenesis. Phenolic acid CGA is the main compound contributing to the inhibition of FL on retinal angiogenesis. PMID- 27196299 TI - Antibiotic-Resistant Neisseria gonorrhoeae Spread Faster with More Treatment, Not More Sexual Partners. AB - The sexually transmitted bacterium Neisseria gonorrhoeae has developed resistance to all antibiotic classes that have been used for treatment and strains resistant to multiple antibiotic classes have evolved. In many countries, there is only one antibiotic remaining for empirical N. gonorrhoeae treatment, and antibiotic management to counteract resistance spread is urgently needed. Understanding dynamics and drivers of resistance spread can provide an improved rationale for antibiotic management. In our study, we first used antibiotic resistance surveillance data to estimate the rates at which antibiotic-resistant N. gonorrhoeae spread in two host populations, heterosexual men (HetM) and men who have sex with men (MSM). We found higher rates of spread for MSM (0.86 to 2.38 y 1, mean doubling time: 6 months) compared to HetM (0.24 to 0.86 y-1, mean doubling time: 16 months). We then developed a dynamic transmission model to reproduce the observed dynamics of N. gonorrhoeae transmission in populations of heterosexual men and women (HMW) and MSM. We parameterized the model using sexual behavior data and calibrated it to N. gonorrhoeae prevalence and incidence data. In the model, antibiotic-resistant N. gonorrhoeae spread with a median rate of 0.88 y-1 in HMW and 3.12 y-1 in MSM. These rates correspond to median doubling times of 9 (HMW) and 3 (MSM) months. Assuming no fitness costs, the model shows the difference in the host population's treatment rate rather than the difference in the number of sexual partners explains the differential spread of resistance. As higher treatment rates result in faster spread of antibiotic resistance, treatment recommendations for N. gonorrhoeae should carefully balance prevention of infection and avoidance of resistance spread. PMID- 27196301 TI - End-of-life care in the head and neck cancer patient. AB - Past the point of no longer being able to control malignancies of the oral cavity and head and neck, the decision-making process must shift to one that essentially concerns itself with creating comfort for the patient. The role of family, physicians, and other caregivers becomes, in many ways, more directed as active neoplasia-related concerns become less relevant. Challenges remain significant in terms of continuing management of prior treatment-related side effects and functional impairments to providers concerning themselves with maintenance of dignity, honoring the wishes of the family, and creating full understanding of on the part of all parties concerned what the goals of treatment cessation and palliation are key as death approaches. PMID- 27196300 TI - Comparison of Removal Behavior of Two Biotrickling Filters under Transient Condition and Effect of pH on the Bacterial Communities. AB - Although biotrickling filters (BTFs) applied under acidic condition to remove H2S from waste gases have been reported, the removal behavior of the acidic BTF under transient condition which was normal in most industry processes, and corresponding bacterial community have not been thoroughly studied. In the present study, two BTFs were run under neutral (BTFn) and acidic (BTFa) conditions, respectively. The results revealed that the removal performance of BTFa under transient condition was superior to that of BTFn; the maximum H2S eliminating capacities (ECs) achieved by BTFa and BTFn were 489.9 g/m3 h and 443.6 g/m3 h, respectively. High-throughput sequencing suggested that pH was the critical factor and several other factors including nutrient and the inlet loadings also had roles in shaping bacterial community structure. Acidithiobacillus was the most abundant bacterial group. The results indicated that BTF acclimation under acidic condition may facilitate generating microbial community with high H2S-degrading capability. PMID- 27196302 TI - Analysis of Body Mass Index and Mortality in Patients With Colorectal Cancer Using Causal Diagrams. AB - IMPORTANCE: Physicians and investigators have sought to determine the relationship between body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]) and colorectal cancer (CRC) outcomes, but methodologic limitations including sampling selection bias, reverse causality, and collider bias have prevented the ability to draw definitive conclusions. OBJECTIVE: To evaluate the association of BMI at the time of, and following, colorectal cancer (CRC) diagnosis with mortality in a complete population using causal diagrams. DESIGN, SETTING, AND PARTICIPANTS: This retrospective observational study with prospectively collected data included a cohort of 3408 men and women, ages 18 to 80 years, from the Kaiser Permanente Northern California population, who were diagnosed with stage I to III CRC between 2006 and 2011 and who also had surgery. EXPOSURES: Body mass index at diagnosis and 15 months following diagnosis. MAIN OUTCOMES AND MEASURES: Hazard ratios (HRs) for all-cause mortality and CRC-specific mortality compared with normal-weight patients, adjusted for sociodemographics, disease severity, treatment, and prediagnosis BMI. RESULTS: This study investigated a cohort of 3408 men and women ages 18 to 80 years diagnosed with stage I to III CRC between 2006 and 2011 who also had surgery. At-diagnosis BMI was associated with all-cause mortality in a nonlinear fashion, with patients who were underweight (BMI <18.5; HR, 2.65; 95% CI, 1.63-4.31) and patients who were class II or III obese (BMI >=35; HR, 1.33; 95% CI, 0.89-1.98) exhibiting elevated mortality risks, compared with patients who were low-normal weight (BMI 18.5 to <23). In contrast, patients who were high normal weight (BMI 23 to <25; HR, 0.77; 95% CI, 0.56-1.06), low-overweight (BMI 25 to <28; HR, 0.75; 95% CI, 0.55-1.04), and high-overweight (BMI 28 to <30; HR, 0.52; 95% CI, 0.35-0.77) had lower mortality risks, and patients who were class I obese (BMI 30 to <35) showed no difference in risk. Spline analysis confirmed a U shaped relationship in participants with lowest mortality at a BMI of 28. Associations with CRC-specific mortality were similar. Associations of postdiagnosis BMI and mortality were also similar, but patients who were class I obese had significantly lower all-cause and cancer-specific mortality risks. CONCLUSIONS AND RELEVANCE: In this study, body mass index at the time of diagnosis and following diagnosis of CRC was associated with mortality risk. Though evidence shows that exercise in patients with cancer should be encouraged, findings suggest that recommendations for weight loss in the immediate postdiagnosis period among patients with CRC who are overweight may be unwarranted. PMID- 27196303 TI - Tyraminergic and Octopaminergic Modulation of Defensive Behavior in Termite Soldier. AB - In termites, i.e. a major group of eusocial insects, the soldier caste exhibits specific morphological characteristics and extremely high aggression against predators. Although the genomic background is identical to the other non aggressive castes, they acquire the soldier-specific behavioral character during the course of caste differentiation. The high aggressiveness and defensive behavior is essential for colony survival, but the neurophysiological bases are completely unknown. In the present study, using the damp-wood termite Hodotermopsis sjostedti, we focused on two biogenic amines, octopamine (OA) and tyramine (TA), as candidate neuromodulators for the defensive behavior in soldiers. High-performance liquid chromatographic analysis revealed that TA levels in the brain and suboesophageal ganglion (SOG) and the OA level in brain were increased in soldiers than in pseudergates (worker caste). Immunohistochemical analysis revealed that TA/OA neurons that innervate specific areas, including the mandibular muscles, antennal nerve, central complex, suboesophageal ganglion, and thoracic and/or abdominal ganglia, were enlarged in a soldier-specific manner. Together with the results that pharmacological application of TA promoted the defensive behavior in pseudergates, these findings suggest that the increased TA/OA levels induce the higher aggressiveness and defensive behavior in termite soldiers. The projection targets of these soldier specific enlarged TA/OA neurons may have important roles in the higher aggressiveness and defensive behavior of the termite soldiers, inducing the neuronal transition that accompanies external morphological changes. PMID- 27196307 TI - Erratum for Euro Surveill. 2016;21(15). PMID- 27196306 TI - Nanofiber Alignment Regulates NIH3T3 Cell Orientation and Cytoskeletal Gene Expression on Electrospun PCL+Gelatin Nanofibers. AB - To examine the influence of substrate topology on the behavior of fibroblasts, tissue engineering scaffolds were electrospun from polycaprolactone (PCL) and a blend of PCL and gelatin (PCL+Gel) to produce matrices with both random and aligned nanofibrous orientations. The addition of gelatin to the scaffold was shown to increase the hydrophilicity of the PCL matrix and to increase the proliferation of NIH3T3 cells compared to scaffolds of PCL alone. The orientation of nanofibers within the matrix did not have an effect on the proliferation of adherent cells, but cells on aligned substrates were shown to elongate and align parallel to the direction of substrate fiber alignment. A microarray of cyotoskeleton regulators was probed to examine differences in gene expression between cells grown on an aligned and randomly oriented substrates. It was found that transcriptional expression of eight genes was statistically different between the two conditions, with all of them being upregulated in the aligned condition. The proteins encoded by these genes are linked to production and polymerization of actin microfilaments, as well as focal adhesion assembly. Taken together, the data indicates NIH3T3 fibroblasts on aligned substrates align themselves parallel with their substrate and increase production of actin and focal adhesion related genes. PMID- 27196308 TI - Production of Biosurfactants by Pseudomonas Species for Application in the Petroleum Industry. AB - The production of surfactants by microorganisms has become an attractive option in the treatment of oil-contaminated environments because biosurfactants are biodegradable and less toxic than synthetic surfactants, although production costs remain high. With the aim of reducing the cost of biosurfactant production, three strains of Pseudomonas (designated P1, P2, and P3) were cultivated in a low cost medium containing molasses and corn steep liquor as substrates. Following the selection of the best producer (P3), a rotational central composite design (RCCD) was used to determine the influence of substrates concentration on surface tension and biosurfactant yield. The biosurfactant reduced the surface tension of water to 27.5 mN/m, and its CMC was determined to be 600 mg/L. The yield was 4.0 g/L. The biosurfactant demonstrated applicability under specific environmental conditions and was able to remove 80 to 90% of motor oil adsorbed to sand. The properties of the biosurfactant suggest its potential application in bioremediation of hydrophobic pollutants. PMID- 27196310 TI - Biochemical characterization of the novel alpha-1, 3-galactosyltransferase WclR from Escherichia coli O3. AB - Glycosyltransferases (GTs) catalyze the formation of regio- and stereo-specific glycosidic linkages between specific sugar donors and recipients. In this study, the function of the gene wclR from the Escherichia coli O3 O-antigen gene cluster that encodes an alpha 1, 3-galactosyltransferase (GalT) that acts on the linkage Gal alpha 1, 3-GlcNAc was biochemically characterized. WclR was expressed in E. coli BL21 (DE3), and the enzymatic product was identified by liquid chromatography-mass spectrometry (LC-MS), collision-induced dissociation electrospray ionization ion trap multiple tandem MS (CID-ESI-IT-MS(n)) and galactosidase digestion, using UDP-Gal as the donor substrate and the synthetic acceptor substrate GlcNAc-PP-De (decyl diphosphate N-acetylglucosamine). The physiochemical properties and the substrate specificity of WclR were investigated. WclR is the first bacterial GalT characterized that acts on the linkage Gal alpha 1, 3-GlcNAc. This study enhanced our knowledge of the diversified functions of GTs and provided a novel enzyme source for possible pharmaceutical application. PMID- 27196309 TI - Mortality, Rehospitalisation and Violent Crime in Forensic Psychiatric Patients Discharged from Hospital: Rates and Risk Factors. AB - OBJECTIVES: To determine rates and risk factors for adverse outcomes in patients discharged from forensic psychiatric services. METHOD: We conducted a historical cohort study of all 6,520 psychiatric patients discharged from forensic psychiatric hospitals between 1973 and 2009 in Sweden. We calculated hazard ratios for mortality, rehospitalisation, and violent crime using Cox regression to investigate the effect of different psychiatric diagnoses and two comorbidities (personality or substance use disorder) on outcomes. RESULTS: Over mean follow-up of 15.6 years, 30% of patients died (n = 1,949) after discharge with an average age at death of 52 years. Over two-thirds were rehospitalised (n = 4,472, 69%), and 40% violently offended after discharge (n = 2,613) with a mean time to violent crime of 4.2 years. The association between psychiatric diagnosis and outcome varied-substance use disorder as a primary diagnosis was associated with highest risk of mortality and rehospitalisation, and personality disorder was linked with the highest risk of violent offending. Furthermore comorbid substance use disorder typically increased risk of adverse outcomes. CONCLUSION: Violent offending, premature mortality and rehospitalisation are prevalent in patients discharged from forensic psychiatric hospitals. Individualised treatment plans for such patients should take into account primary and comorbid psychiatric diagnoses. PMID- 27196311 TI - Structural characterization of the lipoteichoic acid isolated from Staphylococcus sciuri W620. AB - Lipoteichoic acid (LTA) is an important cell envelope compound of Gram-positive bacteria. LTA isolated from allergy-protective Staphylococcus sciuri W620 strain was characterized by chemical analyses as well as 1D and 2D NMR experiments. Compositional analyses indicated the presence of glycerol (Gro), phosphate-Gro, alanine-Gro, glucose (Glc) and fatty acids. The studied strain produced LTA with backbone composed of glycerol-phosphate repeating units only substituted with d alanine (Ala) and the lipid anchor, typically for genus Staphyloccocus, possessing the structure beta-d-Glcp(1->6)- beta-d-Glcp(1->3)-1,2-diacyl-sn-Gro. PMID- 27196312 TI - Efficient chemoenzymatic synthesis of 4-nitrophenyl beta-d-apiofuranoside and its use in screening of beta-d-apiofuranosidases. AB - 4-Nitrophenyl beta-d-apiofuranoside as a chromogenic probe for detection of beta d-apiofuranosidase activity was prepared in 61% yield from 2,3-isopropylidene alpha,beta-d-apiofuranose through a sequence of five reactions. The synthesis involves one regioselective enzymatic step-benzoylation of primary hydroxyl of 2,3-isopropylidene-alpha,beta-d-apiofuranose catalysed by Lipolase 100T and stereoselective beta-d-apiofuranosylation of p-nitrophenol using BF3?OEt2/Et3N. The product was used for screening of beta-d-apiofuranosidase activity in 61 samples of crude commercial enzymes and plant materials. Fifteen enzyme preparations originating from different strains of genera Aspergillus display beta-d-apiofuranosidase activity. The highest activity was found in Rapidase AR 2000 (78.27 U/g) and lyophilized Viscozyme L (64,36 U/g). PMID- 27196313 TI - Synthesis of the 2-deoxy trisaccharide glycal of antitumor antibiotics landomycins A and E. AB - Synthesis of the 2-deoxy trisaccharide glycal of antitumor antibiotics landomycins A and E has been described. The synthesis involves an anomeric O alkylation for the synthesis of 2-deoxy beta-linked disaccharide, a tert butyldimethylsilyl triflate-catalyzed alpha-selective L-rhodinosylation, and a lithium 4,4'-di-tert-butylbiphenyl-mediated reductive debenzylation and concomitant reductive lithiation-elimination for the production of the 2-deoxy trisaccharide glycal. PMID- 27196314 TI - Block synthesis of A (type 2) and B (type 2) tetrasaccharides related to the human ABO blood group system. AB - Herein we report the synthesis of 3-aminopropyl glycosides of A (type 2) and B (type 2) tetrasaccharides via [3 + 1] block scheme. Peracetylated trichloroacetimidates of A and B trisaccharides were used as glycosyl donors. The well-known low reactivity of 4-OH group of N-acetyl-d-glucosamine forced us to test four glucosamine derivatives (3-Bz-1,6-anhydro-GlcNAc and 3 trifluoroacetamidopropyl beta-glycosides of 3-Ac-6-Bn-GlcNAc, 3-Ac-6-Bn-GlcN3, and 3-Ac-6-Bn-GlcNAc2) to select the best glycosyl acceptor for the synthesis of type 2 tetrasaccharides. The desired tetrasacchrides were not isolated, when 3 trifluoroacetamidopropyl glycosyde of 3-Ac-6-Bn-GlcNAcbeta was glycosylated. Glycosylation of 3-Bz-1,6-anhydro-GlcNAc derivative resulted in alpha-glycoside as a major product. High stereospecificity was achieved only in the synthesis of B (type 2) tetrasaccharide, when 3-trifluoroacetamidopropyl 3-Ac-6-Bn-GlcNAc2beta was applied as the glycosyl acceptor (beta/alpha 5:1), whereas glycosylation with trichloroacetimidate of A trisaccharide was not stereospecific (beta/alpha 1.3:1). Glycosylation of 3-trifluoroacetamidopropyl glycoside of 3-Ac-6-Bn GlcN3beta with trichloroacetimidates of A and B trisaccharides provided the same stereochemical yield (beta/alpha 1.5:1). PMID- 27196315 TI - 1,2,3,4,6-Pentakis[-O-(3,4,5-trihydroxybenzoyl)]-alpha,beta-D-glucopyranose (PGG) analogs: design, synthesis, anti-tumor and anti-oxidant activities. AB - 1,2,3,4,6-Pentakis[-O-(3,4,5-trihydroxybenzoyl)]-alpha,beta-D-glucopyranose (PGG) 12 has been reported for its antioxidant activities, where the free OH groups in PGG seem to be critical for activities. To explore PGG-based compounds as chemotherapeutic agents and to analyze the contribution of specific OH groups in PGG for anti-cancer activities, we designed and synthesized a series of 27 benzoic and cinnamic acid analogs of PGG. These analogs were tested for cytotoxicities against two human lung (A549 and H1299) and two human colon (HCT116 and HT29) cancer cell lines. Compound 12 (PGG) had highest cytotoxicities against HCT116 and A549 cells with IC50 of 1.61 uM and 3.02 uM, respectively. In contrast, the compound 16 (1,2,3,4,6-pentakis[-O-(4-hydroxy-3-methoxybenzoyl)] alpha,beta-D-glucopyranose, PVG) was most effective at killing HT29 and H1299 cells with IC50 of 1.76 uM and 3.65 uM, respectively, indicating the mutual contribution of m-methoxy and p-hydroxy groups to the observed cytotoxicities. Moreover, cinnamic acid analogs were less active than the benzoic acid analogs evidenced by higher IC50 values. Furthermore, in cinnamic acid analogs the hydrogenation of double bond to saturated 2-C side chain enhance the cytotoxicities in all four cell lines. Compounds also possess good anti-oxidant and reducing activities. Compound 12 and 26 show the highest antioxidant and reducing activities. PMID- 27196316 TI - Serum Levels of Acyl-Carnitines along the Continuum from Normal to Alzheimer's Dementia. AB - This study aimed to determine the serum levels of free L-carnitine, acetyl-L carnitine and 34 acyl-L-carnitine in healthy subjects and in patients with or at risk of Alzheimer's disease. Twenty-nine patients with probable Alzheimer's disease, 18 with mild cognitive impairment of the amnestic type, 24 with subjective memory complaint and 46 healthy subjects were enrolled in the study, and the levels of carnitine and acyl-carnitines were measured by tandem mass spectrometry. The concentrations of acetyl-L-carnitine progressively decreased passing from healthy subjects group (mean+/-SD, 5.6+/-1.3 MUmol/L) to subjective memory complaint (4.3+/-0.9 MUmol/L), mild cognitive impairment (4.0+/-0.53 MUmol/L), up to Alzheimer's disease (3.5+/-0.6 MUmol/L) group (p<0.001). The differences were significant for the comparisons: healthy subjects vs. subjective memory complaint, mild cognitive impairment or Alzheimer's disease group; and subjective memory complaint vs. Alzheimer's disease group. Other acyl-carnitines, such as malonyl-, 3-hydroxyisovaleryl-, hexenoyl-, decanoyl-, dodecanoyl-, dodecenoyl-, myristoyl-, tetradecenoyl-, hexadecenoyl-, stearoyl-, oleyl- and linoleyl-L-carnitine, showed a similar decreasing trend, passing from healthy subjects to patients at risk of or with Alzheimer's disease. These results suggest that serum acetyl-L-carnitine and other acyl-L-carnitine levels decrease along the continuum from healthy subjects to subjective memory complaint and mild cognitive impairment subjects, up to patients with Alzheimer's disease, and that the metabolism of some acyl-carnitines is finely connected among them. These findings also suggest that the serum levels of acetyl-L-carnitine and other acyl L-carnitines could help to identify the patients before the phenotype conversion to Alzheimer's disease and the patients who would benefit from the treatment with acetyl-L-carnitine. However, further validation on a larger number of samples in a longitudinal study is needed before application to clinical practice. PMID- 27196317 TI - Gene Expression Analysis Indicates Divergent Mechanisms in DEN-Induced Carcinogenesis in Wild Type and Bid-Deficient Livers. AB - Bid is a Bcl-2 family protein. In addition to its pro-apoptosis function, Bid can also promote cell proliferation, maintain S phase checkpoint, and facilitate inflammasome activation. Bid plays important roles in tissue injury and regeneration, hematopoietic homeostasis, and tumorigenesis. Bid participates in hepatic carcinogenesis but the mechanism is not fully understood. Deletion of Bid resulted in diminished tumor burden and delayed tumor progression in a liver cancer model. In order to better understand the Bid-regulated events during hepatic carcinogenesis we performed gene expression analysis in wild type and bid deficient mice treated with a hepatic carcinogen, diethylnitrosamine. We found that deletion of Bid caused significantly fewer alterations in gene expression in terms of the number of genes affected and the number of pathways affected. In addition, the expression profiles were remarkably different. In the wild type mice, there was a significant increase in the expression of growth regulation related and immune/inflammation response-related genes, and a significant decrease in the expression of metabolism-related genes, both of which were diminished in bid-deficient livers. These data suggest that Bid could promote hepatic carcinogenesis via growth control and inflammation-mediated events. PMID- 27196319 TI - MRI Evidence of Cerebellar and Extraocular Muscle Atrophy Differently Contributing to Eye Movement Abnormalities in SCA2 and SCA28 Diseases. AB - PURPOSE: Spinocerebellar ataxias type 2 and 28 (SCA2, SCA28) are autosomal dominant disorders characterized by progressive cerebellar and oculomotor abnormalities. We aimed to investigate cerebellar, brainstem, and extraocular muscle involvement in the mitochondrial SCA28 disease compared with SCA2. METHODS: We obtained orbital and brain 1.5 T-magnetic resonance images (MRI) in eight SCA28 subjects, nine SCA2, and nine age-matched healthy subjects. Automated segmentation of cerebellum and frontal lobe was performed using Freesurfer software. Manual segmentations for midbrain, pons, and extraocular muscles were performed using OsiriX. RESULTS: Eye movement abnormalities in SCA2 subjects were characterized by slow horizontal saccades. Subjects with SCA28 variably presented hypometric saccades, saccadic horizontal pursuit, impaired horizontal gaze holding, and superior eyelid ptosis. Quantitative brain MRI demonstrated that cerebellar and pons volumes were significantly reduced in both SCA2 and SCA28 subjects compared with controls (P < 0.03), and in SCA2 subjects compared with SCA28 (P < 0.01). Midbrain and frontal lobe volumes were also significantly reduced in SCA2 compared to controls (P < 0.03), whereas these volumes did not differ between SCA2 and SCA28 and between SCA28 and control subjects. The extraocular muscle areas were 37% to 48% smaller in SCA28 subjects compared with controls (P < 0.002), and 14% to 36% smaller compared with SCA2 subjects (P < 0.03). Extraocular muscle areas did not differ between SCA2 and controls. CONCLUSIONS: Our MRI findings support the hypothesis of different cerebellar and extraocular myopathic contributions in the eye movement abnormalities in SCA2 and SCA28 diseases. In SCA28, a myopathic defect selectively involving the extraocular muscles supports a specific impairment of mitochondrial energy metabolism. PMID- 27196320 TI - Oxidative Stress-Induced Dysfunction of Muller Cells During Starvation. AB - PURPOSE: Muller cells support retinal neurons with essential functions. Here, we aim to examine the impact of starvation and oxidative stress on glutamate uptake and mitochondrial function in Muller cells. METHODS: Cultured human retinal Muller cells (MIO-M1) were exposed to H2O2 and additional starvation for 24 hours. Effects of starvation and H2O2 on glutamate uptake and mitochondrial function were assessed by kinetic glutamate uptake assays and Seahorse assays, respectively. Cell survival was evaluated by cell viability assays. mRNA and protein expressions were assessed by quantitative PCR and Western blot. RESULTS: Starvation of Muller cells increased the glutamate uptake capacity as well as the expression of the most abundant glutamate transporter, EAAT1. Mitochondrial and glycolytic activity were diminished in starved Muller cells despite unaffected cell viability. Simultaneous starvation and exposure to oxidative stress resulted in a reduced glutamate uptake and a collapsed mitochondrial function. In Muller cells with intact energy supply, the glutamate uptake and mitochondrial function were unaffected after exposure to oxidative stress. CONCLUSIONS: Here, we identify an increased susceptibility toward oxidative stress in starved Muller cells in spite of unaffected viability and an apparent decreased ability to transport glutamate. Solely exposure to oxidative stress did not affect Muller cell functions. Thus, our study suggests an increased susceptibility of Muller cells in case of more than one cellular stressor. Extrapolating these findings, age-related neurodegenerative retinal diseases may be the result of impaired Muller cell function. PMID- 27196318 TI - Vitamin D Induces Global Gene Transcription in Human Corneal Epithelial Cells: Implications for Corneal Inflammation. AB - PURPOSE: Our previous studies show that human corneal epithelial cells (HCEC) have a functional vitamin D receptor (VDR) and respond to vitamin D by dampening TLR-induced inflammation. Here, we further examined the timing of the cytokine response to combined vitamin D-TLR treatment and used genome-wide microarray analysis to examine the effect of vitamin D on corneal gene expression. METHODS: Telomerase-immortalized HCEC (hTCEpi) were stimulated with polyinosinic polycytidylic acid (poly[I:C]) and 1,25-dihydroxyvitamin D3 (1,25D3) for 2 to 24 hours and interleukin (IL)-8 expression was examined by quantitative (q)PCR and ELISA. Telomerase-immortalized HCEC and SV40-HCEC were treated with 1,25D3 and used in genome-wide microarray analysis. Expression of target genes was validated using qPCR in both cell lines and primary HCEC. For confirmation of IkappaBalpha protein, hTCEpi were treated with 1,25D3 for 24 hours and cell lysates used in an ELISA. RESULTS: Treatment with 1,25D3 increased poly(I:C)-induced IL-8 mRNA and protein expression after 2 to 6 hours. However, when cells were pretreated with 1,25D3 for 24 hours, 1,25D3 decreased cytokine expression. For microarray analysis, 308 genes were differentially expressed by 1,25D3 treatment in hTCEpi, and 69 genes in SV40s. Quantitative (q)PCR confirmed the vitamin D-mediated upregulation of target genes, including nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IkappaBalpha). In addition to increased transcript levels, IkappaBalpha protein was increased by 28% following 24 hours of vitamin D treatment. CONCLUSIONS: Microarray analysis demonstrates that vitamin D regulates numerous genes in HCEC and influences TLR signaling through upregulation of IkappaBalpha. These findings are important in dissecting the role of vitamin D at the ocular surface and highlight the need for further research into the functions of vitamin D and its influence on corneal gene expression. PMID- 27196321 TI - The Effect of Statins on Intraocular Pressure and on the Incidence and Progression of Glaucoma: A Systematic Review and Meta-Analysis. AB - PURPOSE: We conducted a systematic review and meta-analysis of observational studies to evaluate the effect of oral statins on intraocular pressure (IOP) and the incidence and progression of glaucoma. METHODS: This was a systematic review of the literature and meta-analysis. Searches of PubMed/Medline and Embase were conducted to include all types of studies. Gray literature abstracts were also considered for inclusion. Last search date was February 2016. Risk of bias was assessed using the Newcastle-Ottawa scale independently by two reviewers. Odds ratios (OR) or hazard ratios (HR) and 95% confidence intervals (CI) were extracted from each study. Pooled ORs for incidence of glaucoma were calculated using a random-effects model. RESULTS: We identified seven cohort studies, three case-control studies, and one cross-sectional study with a total number of 583,615 participants. No randomized controlled trials were retrieved. Pooled ORs demonstrated a statistically significant association between short-term statin use (<=2 years) and reduced incidence of glaucoma (OR 0.96, 95%CI 0.94, 0.99). Pooled ORs of long-term statin use (>2 years) did not demonstrate statistically significant reduction in incidence of glaucoma (OR 0.70, 95%CI 0.46, 1.06). There was inconsistent evidence for the protective effect of statins against the progression of glaucoma, although there was no standard definition for progression across studies. There was no significant difference in IOP associated with statin use. CONCLUSIONS: Short-term statin use is associated with a reduced incidence of glaucoma. The effect of statins on glaucoma progression and IOP is uncertain. PMID- 27196324 TI - Patterns of lymph node metastasis identified following bilateral mandibular and medial retropharyngeal lymphadenectomy in 31 dogs with malignancies of the head. AB - Variable pathways of lymphatic drainage have been described in the dog head and neck. The aim of this study was to retrospectively assess the patterns of lymph node metastasis in dogs with malignancies of the head following bilateral mandibular and medial retropharyngeal lymphadenectomy. Thirty-one dogs were included. Median age at surgery was 10 years (range: 5 months to 14 years) and mean bodyweight was 21.4 +/- 11.9 kg. Lymph node metastasis occurred in 14 dogs (45%), with spread to mandibular lymph nodes in 14 dogs and medial retropharyngeal metastasis in 11 dogs. Eight of 13 dogs (62%) with lymphatic metastasis and a lateralised lesion showed contralateral dissemination, while 12/13 (92%) showed ipsilateral metastasis. Of 13 dogs with oral malignant melanoma, four showed metastasis to all four lymph centres. Contralateral metastasis may occur in dogs with malignancies of the head and should be considered during staging and management. PMID- 27196322 TI - Novel Identity and Functional Markers for Human Corneal Endothelial Cells. AB - PURPOSE: Human corneal endothelial cell (HCEC) density decreases with age, surgical complications, or disease, leading to vision impairment. Such endothelial dysfunction is an indication for corneal transplantation, although there is a worldwide shortage of transplant-grade tissue. To overcome the current poor donor availability, here we isolate, expand, and characterize HCECs in vitro as a step toward cell therapy. METHODS: Human corneal endothelial cells were isolated from cadaveric corneas and expanded in vitro. Cell identity was evaluated based on morphology and immunocytochemistry, and gene expression analysis and flow cytometry were used to identify novel HCEC-specific markers. The functional ability of HCEC to form barriers was assessed by transendothelial electrical resistance (TEER) assays. RESULTS: Cultured HCECs demonstrated canonical morphology for up to four passages and later underwent endothelial-to mesenchymal transition (EnMT). Quality of donor tissue influenced cell measures in culture including proliferation rate. Cultured HCECs expressed identity markers, and microarray analysis revealed novel endothelial-specific markers that were validated by flow cytometry. Finally, canonical HCECs expressed higher levels of CD56, which correlated with higher TEER than fibroblastic HCECs. CONCLUSIONS: In vitro expansion of HCECs from cadaveric donor corneas yields functional cells identifiable by morphology and a panel of novel markers. Markers described correlated with function in culture, suggesting a basis for cell therapy for corneal endothelial dysfunction. PMID- 27196323 TI - Sequence and Expression of Complement Factor H Gene Cluster Variants and Their Roles in Age-Related Macular Degeneration Risk. AB - PURPOSE: To investigate how potentially functional genetic variants are coinherited on each of four common complement factor H (CFH) and CFH-related gene haplotypes and to measure expression of these genes in eye and liver tissues. METHODS: We sequenced the CFH region in four individuals (one homozygote for each of four common CFH region haplotypes) to identify all genetic variants. We studied associations between the haplotypes and AMD phenotypes in 2157 cases and 1150 controls. We examined RNA-seq profiles in macular and peripheral retina and retinal pigment epithelium/choroid/sclera (RCS) from eight eye donors and three liver samples. RESULTS: The haplotypic coinheritance of potentially functional variants (including missense variants, novel splice sites, and the CFHR3-CFHR1 deletion) was described for the four common haplotypes. Expression of the short and long CFH transcripts differed markedly between the retina and liver. We found no expression of any of the five CFH-related genes in the retina or RCS, in contrast to the liver, which is the main source of the circulating proteins. CONCLUSIONS: We identified all genetic variants on common CFH region haplotypes and described their coinheritance. Understanding their functional effects will be key to developing and stratifying AMD therapies. The small scale of our expression study prevented us from investigating the relationships between CFH region haplotypes and their expression, and it will take time and collaboration to develop epidemiologic-scale studies. However, the striking difference between systemic and ocular expression of complement regulators shown in this study suggests important implications for the development of intraocular and systemic treatments. PMID- 27196331 TI - Long-term care for patients with coeliac disease in the UK: a review of the literature and future directions. AB - Coeliac disease is a common digestive disorder that affects 1% of adults. It is characterised by mucosal damage of the small intestine caused by dietary gluten. The main treatment for coeliac disease is a lifelong gluten-free diet, which can reduce morbidity and mortality and also improve quality of life. Despite the benefits, adhering to this diet is often challenging, with patients often struggling to sustain dietary restriction. Structured follow-up for coeliac disease is recommended in international guidelines for improving adherence and for detecting complications;however, uncertainty exists concerning exactly who should be administering this follow-up care. Here, we undertake a review of the current approaches described in the literature to follow-up patients with coeliac disease, and assess the efficacy of these differing models. We also explore future directions for the care of these patients in the context of the UK National Health Service (a publicly funded healthcare system). Although the focus of this review pertains to follow-up within the UK healthcare system, these problems are recognised to be international, and so the findings of our review are likely to be of interest to all healthcare professionals seeing and managing patients with coeliac disease. PMID- 27196332 TI - An Indirect Comparison of Efficacy and Safety of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate and Abacavir/Lamivudine + Dolutegravir in Initial Therapy. AB - OBJECTIVES: The objective of this analysis is to perform an indirect comparison of elvitegravir, cobicistat, emtricitabine and tenofovir DF (E/C/F/TDF) to abacavir/lamivudine and dolutegravir (ABC/3TC + DTG) by using 2 trials evaluating each of these regimens in comparison to efavirenz, emtricitabine and tenofovir DF (EFV/FTC/TDF). METHODS: An indirect comparison was performed by using a generalization of Bucher's methodology to calculate risk differences. Two phase III clinical trials (GS-US-236-0102 and SINGLE-described above) were used. RESULTS: Results of the indirect comparison showed no statistically significant risk difference of the efficacy endpoint of achieving HIV RNA < 50 copies/mL between E/C/F/TDF and ABC/3TC + DTG for the ITT population at weeks 48, 96 and 144: respectively -3.7% (CI95% = [-10.8%; 3.4%]), -5.2% (CI95% = [-13.2%; 2.8%]) and -3.1% (CI95% = [-12.0%; 5.7%]). There was no statistically significant differences in the risk difference for serious adverse events (5.7% (CI95% = [ 2.2%; 12.3%])), drug related adverse event (2.7% (CI95% = [-7.0%;12.4%])), drug related serious adverse event (0.8% (CI95% = [-1.6%;3.2%])) and death (0.5% (CI95% = [-0.8%;1.8%])), respectively, between E/C/F/TDF and ABC/3TC + DTG. A significant difference was found for discontinuation due to adverse events with a higher rate for E/C/F/TDF (difference = 8.6% (CI95% = [3.3%; 13.9%])). There was also no statistically significant risk difference of the viral resistance of 1.2% (CI95% = [-1.2; 3.7]) between E/C/F/TDF and ABC/3TC + DTG at week 48, 1.7% at week 96 (CI95% = [-1.1; 4.5]) and 2.2% (CI95% = [-1.0; 5.4]) at week 144. PMID- 27196333 TI - Neural mechanisms of face perception, their emergence over development, and their breakdown. AB - Face perception is probably the most developed visual perceptual skill in humans, most likely as a result of its unique evolutionary and social significance. Much recent research has converged to identify a host of relevant psychological mechanisms that support face recognition. In parallel, there has been substantial progress in uncovering the neural mechanisms that mediate rapid and accurate face perception, with specific emphasis on a broadly distributed neural circuit, comprised of multiple nodes whose joint activity supports face perception. This article focuses specifically on the neural underpinnings of face recognition, and reviews recent structural and functional imaging studies that elucidate the neural basis of this ability. In addition, the article covers some of the recent investigations that characterize the emergence of the neural basis of face recognition over the course of development, and explores the relationship between these changes and increasing behavioural competence. This paper also describes studies that characterize the nature of the breakdown of face recognition in individuals who are impaired in face recognition, either as a result of brain damage acquired at some point or as a result of the failure to master face recognition over the course of development. Finally, information regarding similarities between the neural circuits for face perception in humans and in nonhuman primates is briefly covered, as is the contribution of subcortical regions to face perception. WIREs Cogn Sci 2016, 7:247-263. doi: 10.1002/wcs.1388 For further resources related to this article, please visit the WIREs website. PMID- 27196334 TI - Retraction: Resistance to DDT and Pyrethroids and Increased kdr Mutation Frequency in An. gambiae after the Implementation of Permethrin-Treated Nets in Senegal. PMID- 27196335 TI - Anti-inflammatory and Quinone Reductase Inducing Compounds from Fermented Noni (Morinda citrifolia) Juice Exudates. AB - A new fatty acid ester disaccharide, 2-O-(beta-d-glucopyranosyl)-1-O-(2E,4Z,7Z) deca-2,4,7-trienoyl-beta-d-glucopyranose (1), a new ascorbic acid derivative, 2 caffeoyl-3-ketohexulofuranosonic acid gamma-lactone (2), and a new iridoid glycoside, 10-dimethoxyfermiloside (3), were isolated along with 13 known compounds (4-16) from fermented noni fruit juice (Morinda citrifolia). The structures of the new compounds, together with 4 and 5, were determined by 1D and 2D NMR experiments, as well as comparison with published values. Compounds 2 and 7 showed moderate inhibitory activities in a TNF-alpha-induced NF-kappaB assay, and compounds 4 and 6 exhibited considerable quinone reductase-1 (QR1) inducing effects. PMID- 27196336 TI - Human African Trypanosomiasis in the Kafue National Park, Zambia. PMID- 27196337 TI - Response to comment on "Chemosignalling effects of human tears revisited: Does exposure to female tears decrease males' perception of female sexual attractiveness?" PMID- 27196338 TI - Cell-Imprinted Substrates Modulate Differentiation, Redifferentiation, and Transdifferentiation. AB - Differentiation of stem cells into mature cells through the use of physical approaches is of great interest. Here, we prepared smart nanoenvironments by cell imprinted substrates based on chondrocytes, tenocytes, and semifibroblasts as templates and demonstrated their potential for differentiation, redifferentiation, and transdifferentiation. Analysis of shape and upregulation/downregulation of specific genes of stem cells, which were seeded on these cell-imprinted substrates, confirmed that imprinted substrates have the capability to induce specific shapes and molecular characteristics of the cell types that were used as templates for cell-imprinting. Interestingly, immunofluorescent staining of a specific protein in chondrocytes (i.e., collagen type II) confirmed that adipose-derived stem cells, semifibroblasts, and tenocytes can acquire the chondrocyte phenotype after a 14 day culture on chondrocyte-imprinted substrates. In summary, we propose that common polystyrene tissue culture plates can be replaced by this imprinting technique as an effective and promising way to regulate any cell phenotype in vitro with significant potential applications in regenerative medicine and cell-based therapies. PMID- 27196353 TI - Is It Time for Integrase Inhibitors to be the Preferred Regimen for the First Line Treatment of HIV-1-Infected Naive Patients? AB - Thanks to the emergence of combination antiretroviral therapy, HIV/AIDS has been transformed into a manageable, chronic condition in just 30 years and the life expectancy of patients living with HIV is now comparable to those without. Recent data (START) support the strategy of starting all HIV-positive patients regardless of CD4 count. However, patients and physicians want more than just viral control: they want better tolerability, convenience, and few drug-drug interactions. Are the guidelines right in recommending an integrase inhibitor based regimen as the first-line treatment of choice? PMID- 27196354 TI - Prevalence and Disease Burden of HCV Coinfection in HIV Cohorts in the Asia Pacific Region: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Estimates of the prevalence and disease burden of HIV/HCV coinfection in the Asia Pacific Region are uncertain. METHODS: A systematic review of indexed (PubMed, Embase and Web of Science) and non-indexed cross-sectional and cohort studies (2009-2015) reporting HCV seroprevalence in HIV-positive adults living in the Asia Pacific region was performed. Pooled prevalence estimates were calculated with a DerSimonian-Laird random-effects model. RESULTS: 39 studies from 10 countries in the Asia Pacific region comprising 89,452 HIV-positive individuals were included. In the high-income Asia Pacific region, HCV coinfection prevalence was 3.8% (95% confidence interval (CI): 3.1-4.5) in Singapore. In East Asia, HCV coinfection prevalence was 8.0% (95% CI: 6.4-9.8) in Hong Kong and 25.5% (95% CI: 17.5-34.4) in general HIV cohorts in China. In South Asia, HCV coinfection prevalence was 4.1% (95% CI: 1.7-7.3) in India and 42.6% (95% CI: 38.7-46.5) in Nepal. In Southeast Asia, HCV coinfection prevalence was 5.5% (95% CI: 4.9-6.1) in Cambodia, 5.3% (95% CI: 4.9-5.7) in Myanmar, and 5.1% (95% CI: 2.7-8.2) in Thailand, but higher in Vietnam (42.5%; 95% CI: 40.8-44.2) and Indonesia (17.9%; 95% CI: 15.0-20.9). The prevalence of HCV coinfection was higher in subpopulations of people who inject drugs (China 81.6%; 95% CI: 74.1 88.0; Nepal 80.8%; 95% CI: 76.4-84.9; Indonesia 81.6%; 95% CI: 71.1-90.3), former blood donors (China 82.9%; 95% CI: 73.9-90.3), and blood transfusion recipients (China 51.0%; 95% CI: 41.7-60.2). CONCLUSION: HCV coinfection prevalence within HIV populations is highly variable in the Asia Pacific region, between countries and at-risk populations. Enhanced epidemiological data is required to support scale-up of interferon-free HCV therapy. PMID- 27196355 TI - Report from the International Conference on Viral Hepatitis (ICVH), San Francisco, March 2016. AB - The International Conference on Viral Hepatitis 2016 brought exciting news on the treatment of viral hepatitis. The conference was mainly focused on the most recent estimates of burden for HBV and HCV; the current gaps and prospects for regional and global HCV eradication; the use of HCV treatment as prevention; and the management of difficult-to-cure hepatitis C patients, including individuals who fail on direct-acting antivirals, people who inject drugs, and those with decompensated cirrhosis or renal insufficiency. Special patient populations, such as children, pregnant women, HIV-coinfected and persons with acute hepatitis C, were addressed separately. Data from both clinical trials and real-world experience were discussed. Further debates focused on hepatic conditions that may alter the management and outcome of viral hepatitis, such as fatty liver disease, liver transplantation, and hepatocellular carcinoma. PMID- 27196356 TI - Drug Interactions with Cobicistat- or Ritonavir-Boosted Elvitegravir. AB - Cobicistat and ritonavir are structurally distinct compounds that both potently inhibit cytochrome P450 (CYP) 3A, the metabolizing enzyme primarily responsible for the elimination of several antiretroviral medications, and, as such, are pharmacokinetic boosters for antiretroviral agents that require longer dosing intervals. Recently, cobicistat was approved for the treatment of HIV-1 infection in treatment-naive adults as a component of a single-tablet regimen consisting of cobicistat-boosted elvitegravir plus emtricitabine and tenofovir disoproxil fumarate. While studies have demonstrated that boosting with either cobicistat or ritonavir results in comparable plasma exposure of the target antiretroviral agent, a better understanding of drug-drug interactions between cobicistat- and ritonavir-boosted antiretrovirals and other medications will inform treatment decisions in HIV-infected patients. In connection with their distinct structural properties, COBI and RTV differ with respect to their drug-drug interaction profiles. Compared with ritonavir, cobicistat lacks induction potential and is a more specific inhibitor of 3A and therefore, has reduced effects on other CYP isoforms. To date, more studies have assessed ritonavir drug-drug interactions with other medications than have assessed cobicistat drug-drug interactions. The objective of this article is to review the drug-drug interactions when cobicistat or ritonavir-boosted elvitegravir, cobicistat, or elvitegravir/cobicistat/emtricitabine/tenofovir are coadministered with antiretroviral therapies or drugs that are either substrates, inducers, or inhibitors of the CYP3A metabolic pathway, as well as with drugs that alter intra gastric pH or are substrates of P-gp, in order to inform the proper use of elvitegravir/cobicistat/emtricitabine/tenofovir. PMID- 27196357 TI - Na2ZnGe2S6: A New Infrared Nonlinear Optical Material with Good Balance between Large Second-Harmonic Generation Response and High Laser Damage Threshold. AB - The development of frequency-conversion technology in the infrared region is in urgent need of new excellent infrared nonlinear optical (IR NLO) materials. How to achieve a good balance between laser damage threshold (LDT) and NLO coefficient (dij) for new IR NLO candidates is still a challenge. The combination of the highly electropositive alkali metal (Na) and Zn with d(10) electronic configuration into crystal structure affords one new IR NLO material, Na2ZnGe2S6. It exhibits excellent properties including a wide transparent region (0.38-22 MUm), large band gap (3.25 eV), and especially a balance between a strong NLO coefficient (30-fold that of KDP) and a high LDT (6-fold that of AgGaS2), indicating a promising application in the IR region. Moreover, novel common vertex-linked wavelike infinity[GeS3]n chains are interestingly discovered in Na2ZnGe2S6, which rarely exist in the reported thiogermanides containing alkali metals. In addition, calculated SHG density and dipole moment demonstrate that the large NLO response is mainly attributed to the cooperative effects of the [GeS4] and [ZnS4] units. PMID- 27196358 TI - Clinical Safety and Feasibility of the Advanced Bolus Calculator for Type 1 Diabetes Based on Case-Based Reasoning: A 6-Week Nonrandomized Single-Arm Pilot Study. AB - BACKGROUND: The Advanced Bolus Calculator for Diabetes (ABC4D) is an insulin bolus dose decision support system based on case-based reasoning (CBR). The system is implemented in a smartphone application to provide personalized and adaptive insulin bolus advice for people with type 1 diabetes. We aimed to assess proof of concept, safety, and feasibility of ABC4D in a free-living environment over 6 weeks. METHODS: Prospective nonrandomized single-arm pilot study. Participants used the ABC4D smartphone application for 6 weeks in their home environment, attending the clinical research facility weekly for data upload, revision, and adaptation of the CBR case base. The primary outcome was postprandial hypoglycemia. RESULTS: Ten adults with type 1 diabetes, on multiple daily injections of insulin, mean (standard deviation) age 47 (17), diabetes duration 25 (16), and HbA1c 68 (16) mmol/mol (8.4 (1.5) %) participated. A total of 182 and 150 meals, in week 1 and week 6, respectively, were included in the analysis of postprandial outcomes. The median (interquartile range) number of postprandial hypoglycemia episodes within 6-h after the meal was 4.5 (2.0-8.2) in week 1 versus 2.0 (0.5-6.5) in week 6 (P = 0.1). No episodes of severe hypoglycemia occurred during the study. CONCLUSION: The ABC4D is safe for use as a decision support tool for insulin bolus dosing in self-management of type 1 diabetes. A trend suggesting a reduction in postprandial hypoglycemia was observed in the final week compared with week 1. PMID- 27196359 TI - A Calsequestrin-1 Mutation Associated with a Skeletal Muscle Disease Alters Sarcoplasmic Ca2+ Release. AB - An autosomal dominant protein aggregate myopathy, characterized by high plasma creatine kinase and calsequestrin-1 (CASQ1) accumulation in skeletal muscle, has been recently associated with a missense mutation in CASQ1 gene. The mutation replaces an evolutionarily-conserved aspartic acid with glycine at position 244 (p.D244G) of CASQ1, the main sarcoplasmic reticulum (SR) Ca2+ binding and storage protein localized at the terminal cisternae of skeletal muscle cells. Here, immunocytochemical analysis of myotubes, differentiated from muscle-derived primary myoblasts, shows that sarcoplasmic vacuolar aggregations positive for CASQ1 are significantly larger in CASQ1-mutated cells than control cells. A strong co-immuno staining of both RyR1 and CASQ1 was also noted in the vacuoles of myotubes and muscle biopsies derived from patients. Electrophysiological recordings and sarcoplasmic Ca2+ measurements provide evidence for less Ca2+ release from the SR of mutated myotubes when compared to that of controls. These findings further clarify the pathogenic nature of the p.D244G variant and point out defects in sarcoplasmic Ca2+ homeostasis as a mechanism underlying this human disease, which could be distinctly classified as "CASQ1-couplonopathy". PMID- 27196360 TI - Validity and reliability of a video questionnaire to assess physical function in older adults. AB - BACKGROUND: Self-report questionnaires are widely used to assess physical function in older adults. However, they often lack a clear frame of reference and hence interpreting and rating task difficulty levels can be problematic for the responder. Consequently, the usefulness of traditional self-report questionnaires for assessing higher-level functioning is limited. Video-based questionnaires can overcome some of these limitations by offering a clear and objective visual reference for the performance level against which the subject is to compare his or her perceived capacity. Hence the purpose of the study was to develop and validate a novel, video-based questionnaire to assess physical function in older adults independently living in the community. METHODS: A total of 61 community living adults, 60years or older, were recruited. To examine validity, 35 of the subjects completed the video questionnaire, two types of physical performance tests: a test of instrumental activity of daily living (IADL) included in the Short Physical Functional Performance battery (PFP-10), and a composite of 3 performance tests (30s chair stand, single-leg balance and usual gait speed). To ascertain reliability, two-week test-retest reliability was assessed in the remaining 26 subjects who did not participate in validity testing. RESULTS: The video questionnaire showed a moderate correlation with the IADLs (Spearman rho=0.64, p<0.001; 95% CI (0.4, 0.8)), and a lower correlation with the composite score of physical performance tests (Spearman rho=0.49, p<0.01; 95% CI (0.18, 0.7)). The test-retest assessment yielded an intra-class correlation (ICC) of 0.87 (p<0.001; 95% CI (0.70, 0.94)) and a Cronbach's alpha of 0.89 demonstrating good reliability and internal consistency. CONCLUSIONS: Our results show that the video questionnaire developed to evaluate physical function in community-living older adults is a valid and reliable assessment tool; however, further validation is needed for definitive conclusions. PMID- 27196361 TI - Vascular Alterations in a Murine Model of Acute Graft-Versus-Host Disease Are Associated with Decreased Serum Levels of Adiponectin and an Increased Activity and Vascular Expression of Indoleamine 2,3-Dioxygenase. AB - Graft-versus-host disease (GVHD) is the limiting complication after bone marrow transplantation (BMT), and its pathophysiology seems to be highly influenced by vascular factors. Our study aimed at elucidating possible mechanisms involved in vascular GVHD. For this purpose, we used a fully MHC-mismatched model of BALB/c mice conditioned according to two different intensity protocols with total body irradiation and transplantation of allogeneic (C57BL/6) or syngeneic bone marrow cells and splenocytes. Mesenteric resistance arteries were studied in a pressurized myograph. We also quantified the expression of indoleamine 2,3 dioxygenase (IDO), endothelial (eNOS), and inducible NO synthase (iNOS), as well as several pro- and anti-inflammatory cytokines. We measured the serum levels of tryptophan (trp) and kynurenine (kyn), the kyn/trp ratio (KTR) as a marker of IDO activity, and adiponectin (APN). The myographic study showed a correlation of GVHD severity after allogeneic BMT with functional vessel alterations that started with increased vessel stress and ended in eccentric vessel remodeling, increased vessel strain, and endothelial dysfunction. These alterations were accompanied by increasing IDO activity and decreasing APN levels in the serum of allogeneic animals. The mRNA expression showed significantly elevated IDO, decreased eNOS, and elevation of most studied pro- and anti-inflammatory cytokines. Our study provides further data supporting the importance of vessel alterations in GVHD and is the first to show an association of vascular GVHD with hypoadiponectinemia and an increased activity and vascular expression of IDO. Whether there is also a causative involvement of these two factors in the development of GVHD needs to be further investigated. PMID- 27196362 TI - Lanthanide-Directed Fabrication of Four Tetranuclear Quadruple Stranded Helicates Showing Magnetic Refrigeration and Slow Magnetic Relaxation. AB - A rare class of four tetranuclear lanthanide based quadruple stranded helicates namely, [Ln4L4(OH)2](OAc)2.xH2O (Ln = Gd(III)(1), Dy(III)(2) and x = 4, 5 respectively), [Er4L4(OH)2](NO3)2.9H2O (3), and [Dy4L4(NO3)](NO3)2.2CH3OH.H2O (4) were synthesized by employing succinohydrazone derived bis-tridentate ligand (H2L) and characterized. Structures of 1-3 are similar to each other except the nature of counterions and number of lattice water molecules. In 4, a distorted nitrate ion was arranged in a hexagonal manner holding four dysprosium centers in a slightly twisted manner. Because of the symmetrical nature of each complex, the C4 axis crosses the center of helicate resulting a pseudo-D4 coordination environment. Each ligand coordinates to lanthanide centers in helical manner forming mixture of left (Lambda) and right (Delta) handed discrete units. Complex 1 exhibits antiferromagnetic exchange interaction between nearby Gd(III) centers and shows magnetic refrigeration (-DeltaSm = 24.4 J kg(-1) K(-1) for DeltaH = 7 T at 3 K). AC magnetic susceptibility measurements of 2 and 4 demonstrate slow relaxation behavior, with Ueff (effective energy barrier) of 20.5 and 4.6 K, respectively. As per our knowledge, complexes 1, 2, and 4 represent the first examples of aesthetically pleasing quadruple stranded helicates showing potential magnetocaloric effect and single-molecule-magnet-like behavior. PMID- 27196364 TI - Alleviating salt stress in tomato seedlings using Arthrobacter and Bacillus megaterium isolated from the rhizosphere of wild plants grown on saline-alkaline lands. AB - Salt-induced soil degradation is common in farmlands and limits the growth and development of numerous crop plants in the world. In this study, we isolated salt tolerant bacteria from the rhizosphere of Tamarix chinensis, Suaeda salsa and Zoysia sinica, which are common wild plants grown on a saline-alkaline land, to test these bacteria's efficiency in alleviating salt stress in tomato plants. We screened out seven strains (TF1-7) that are efficient in reducing salt stress in tomato seedlings. The sequence data of 16S rRNA genes showed that these strains belong to Arthrobacter and Bacillus megaterium. All strains could hydrolyze casein and solubilize phosphate, and showed at least one plant growth promotion (PGP)-related gene, indicating their potential in promoting plant growth. The Arthrobacter strains TF1 and TF7 and the Bacillus megaterium strain TF2 and TF3 could produce indole acetic acid under salt stress, further demonstrating their PGP potential. Tomato seed germination, seedling length, vigor index, and plant fresh and dry weight were enhanced by inoculation of Arthrobacter and B. megaterium strains under salt stress. Our results demonstrated that salt-tolerant bacteria isolated from the rhizosphere of wild plants grown on saline-alkaline lands could be used for alleviating salt stress in crop plants. PMID- 27196363 TI - Synthesis of enantiomerically pure [14 C]-labelled morpholine derivatives for a class of trace amine-associate receptor 1 agonists. AB - Various agonists of the trace amine-associate receptor 1, under consideration as potential clinical development candidates, were labelled with carbon-14 for use in preclinical in vitro and in vivo drug metabolism studies. Herein, the [14 C] radiosynthesis of 2-phenyl-substituted morpholines 1 is described. After evaluating and optimizing different synthetic routes, 4-iodonitrobenzene 3 was selected as starting material for the 14-step synthesis. Incorporation of carbon 14 into the acetyl moiety allowed a safe and efficient synthesis of [14 C] labelled 4-nitroacetophenone 2 in five steps and 38% yield. Further transformation of 2 to the target compounds 1 was achieved in a 9-step synthesis. In a representative example, [14 C]-labelled 1 was obtained in an overall yield of 11% and was isolated in >99% radiochemical purity and a specific activity of 47 mCi/mmol. PMID- 27196365 TI - How Can We Best Describe the Cardiac Components? PMID- 27196366 TI - Covalently-layers of PVA and PAA and in situ formed Ag nanoparticles as versatile antimicrobial surfaces. AB - The in situ synthesis of silver nanoparticles (AgNPs) within covalently-modified poly(ethylene terephthalate) (PET) films possessing ultra-thin layer of poly(vinyl alcohol) (PVA) and poly(acrylic acid) (PAA) is successfully demonstrated. The resulting polymeric films are shown to exhibit antimicrobial activities toward Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria and fungus (Candida albicans). To make the films, first PET surfaces were subject to photo-oxidation and subsequent solid-state grafting to attach a PVA layer, followed by a PAA layer. To synthesize the AgNPs inside the films, the PVA and PAA-modified PET was soaked in AgNO3 solution and the polymeric film was modified with the Ag(+) ions via Ag(+)-carboxylate interaction, and then the Ag(+) ions-containing polymer film was subject to either photo-reduction or thermal reduction processes. The PVA and PAA thin layers attached by covalent bonds to the PET surface uniquely promoted not only the in situ synthesis but also the stabilization of AgNPs. The formation of the AgNPs was confirmed by UV-vis spectroscopy or by monitoring the surface plasmon resonance (SPR) peak associated with AgNPs. The resulting PVA and PAA ultrathin layers modified and AgNPs containing PET served as bactericide and fungicide, inhibiting the growth of bacteria and fungi on the surfaces. Given PET's versatility and common use in many commercial processes, the method can be used for producing plastic surfaces with versatile antimicrobial and antibacterial properties. PMID- 27196367 TI - Highly selective BTX from catalytic fast pyrolysis of lignin over supported mesoporous silica. AB - The post synthesis of Al(3+) or Zr(4+) substituted MCM-48 framework with controlled acidity is challenging because the functional groups exhibiting acidity often jeopardize the framework integrity. Herein, we report the post synthesis of two hierarchically porous MCM-48 composed of either aluminum (Al(3+)) or zirconium (Zr(4+)) clusters with high throughput. All prepared catalysts have been characterized by HR-TEM, XRD, IR, N2-adsorption, NH3-TPD, TGA and MAS NMR. They exhibit BET surface areas of 597 and 1112m(2)g(-1) for 8.4% Al/MCM-48 and 2.9% Zr/MCM-48, respectively. XRD analysis reveals that the hierarchical porosity of parental MCM-48 is reserved even after incorporation of Al(3+)or Zr(4+). Zr/MCM-48 catalysts are demonstrate a superior performance versus that of Al/MCM-48 and MCM-48 because of the mild (ZrO2) or nil (SiO2) Lewis acidity contributed from Zr-MU2-O group as well as smaller pore sizes suitable for the restriction of unwanted side reactions. The reaction conditions which were affecting the catalytic pyrolysis and final products were gas flow rate, pyrolysis temperature, and catalyst to lignin ratio. A total of 49% of BTX product were obtained over 2.9% Zr/MCM-48 at 600 degrees C. The Lewis acid character was the governing factor which helps in pyrolysis and directly affects the BTX formation. PMID- 27196368 TI - Why Chitosan? From properties to perspective of mucosal drug delivery. AB - Non-parenteral drug delivery routes primarily remove the local pain at the injection site. The drugs administered through the oral route encounter the process of hepatic first pass metabolism. Among the alternative delivery routes, mucosal route is being investigated as the most preferred route. Different mucosal routes include the gastrointestinal tract (oral), vagina, buccal cavity and nasal cavity. Novel formulations are being developed using natural and synthetic polymers that could increase the residence time of the drug at mucosal surface in order to facilitate permeation and reduce (or bypass) the first pass metabolism. For recombinant drugs, the formulations are accompanied by enzyme inhibitors and penetration enhancers. Buccal cavity (buccal and sublingual mucosa) has smaller surface area than the gastrointestinal tract but the drugs can easily escape the first pass metabolism. Chitosan is the most applied natural polymer while synthetic polymers include Carbopol and Eudragit. Chitosan has inherent properties of mucoadhesion and penetration enhancement apart from biodegradability and efflux pump inhibition. This review hoards the important research purview of chitosan as a compatible drug carrier macromolecule for mucosal delivery on single platform. PMID- 27196369 TI - The spectrum of orofacial manifestations in systemic sclerosis: a challenging management. AB - Systemic sclerosis (SSc) is a rare multisystem connective tissue disorder characterized by the triad fibrosis, vasculopathy and immune dysregulation. This chronic disease has a significant impact on the orofacial region that is involved in more than two-thirds of the cases. SSc patients can show a wide array of oral manifestations, which are usually associated with a severe impairment of the quality of life. They often present a decreased the salivary flow and a reduced mouth opening that contribute substantially to the worsening of the oral health status. Therefore, SSc patients require specific and multidisciplinary interventions that should be initiated as early as possible. The identification of specific radiological and clinical signs at the early stage will improve the management of such patients. This study reviews the wide spectrum of orofacial manifestations associated with SSc and suggests clues for the oral management that remains challenging. PMID- 27196371 TI - Transcriptional repression of p27 is essential for murine embryonic development. AB - The Nczf gene has been identified as one of Ncx target genes and encodes a novel KRAB zinc-finger protein, which functions as a sequence specific transcriptional repressor. In order to elucidate Nczf functions, we generated Nczf knockout (Nczf /-) mice. Nczf-/- mice died around embryonic day 8.5 (E8.5) with small body size and impairment of axial rotation. Histopathological analysis revealed that the cell number decreased and pyknotic cells were occasionally observed. We examined the expression of cell cycle related genes in Nczf-/- mice. p27 expression was increased in E8.0 Nczf-/- mice compared to that of wild type mice. Nczf knockdown by siRNA resulted in increased expression of p27 in mouse embryonic fibroblasts (MEFs). Furthermore, p27 promoter luciferase reporter gene analysis confirmed the regulation of p27 mRNA expression by Nczf. Nczf-/-; p27-/- double knockout mice survived until E11.5 and the defect of axial rotation was restored. These data suggest that p27 repression by Nczf is essential in the developing embryo. PMID- 27196370 TI - Rubella immunity among pregnant women aged 15-44 years, Namibia, 2010. AB - BACKGROUND: The level of rubella susceptibility among women of reproductive age in Namibia is unknown. Documenting the risk of rubella will help estimate the potential burden of disease in Namibian women and the risk of congenital rubella syndrome (CRS) in infants, and will guide strategies for the introduction of rubella vaccine. METHODS: A total of 2044 serum samples from pregnant Namibian women aged 15-44 years were tested for rubella immunoglobulin G antibody; the samples were obtained during the 2010 National HIV Sentinel Survey. The proportion of women seropositive for rubella was determined by 5-year age strata, and factors associated with seropositivity were analyzed by logistic regression, including age, gravidity, HIV status, facility type, and urban/rural status. RESULTS: Overall rubella seroprevalence was 85% (95% confidence interval (CI) 83 86%). Seroprevalence varied by age group (83-90%) and health district (71-100%). In the multivariable model, women from urban residences had higher odds of seropositivity as compared to women from rural residences (odds ratio 1.40, 95% CI 1.09-1.81). CONCLUSIONS: In the absence of a routine rubella immunization program, the high level of rubella seropositivity suggests rubella virus transmission in Namibia, yet 15% of pregnant Namibian women remain susceptible to rubella. The introduction of rubella vaccine will help reduce the risk of rubella in pregnant women and CRS in infants. PMID- 27196373 TI - A universal mechanism generating clusters of differentiated loci during divergence-with-migration. AB - Genome-wide patterns of genetic divergence reveal mechanisms of adaptation under gene flow. Empirical data show that divergence is mostly concentrated in narrow genomic regions. This pattern may arise because differentiated loci protect nearby mutations from gene flow, but recent theory suggests this mechanism is insufficient to explain the emergence of concentrated differentiation during biologically realistic timescales. Critically, earlier theory neglects an inevitable consequence of genetic drift: stochastic loss of local genomic divergence. Here, we demonstrate that the rate of stochastic loss of weak local differentiation increases with recombination distance to a strongly diverged locus and, above a critical recombination distance, local loss is faster than local "gain" of new differentiation. Under high migration and weak selection, this critical recombination distance is much smaller than the total recombination distance of the genomic region under selection. Consequently, divergence between populations increases by net gain of new differentiation within the critical recombination distance, resulting in tightly linked clusters of divergence. The mechanism responsible is the balance between stochastic loss and gain of weak local differentiation, a mechanism acting universally throughout the genome. Our results will help to explain empirical observations and lead to novel predictions regarding changes in genomic architectures during adaptive divergence. PMID- 27196372 TI - OBE3 and WUS Interaction in Shoot Meristem Stem Cell Regulation. AB - The stem cells in the shoot apical meristem (SAM) are the origin of all above ground tissues in plants. In Arabidopsis thaliana, shoot meristem stem cells are maintained by the homeobox transcription factor gene WUS (WUSCHEL) that is expressed in cells of the organizing center underneath the stem cells. In order to identify factors that operate together with WUS in stem cell maintenance, we performed an EMS mutant screen for modifiers of the hypomorphic wus-6 allele. We isolated the oberon3-2 (obe3-2) mutant that enhances stem cell defects in wus-6, but does not affect the putative null allele wus-1. The OBE3 gene encodes a PHD (Plant Homeo Domain) protein that is thought to function in chromatin regulation. Single mutants of OBE3 or its closest homolog OBE4 do not display any defects, whereas the obe3-2 obe4-2 double mutant displays broad growth defects and developmental arrest of seedlings. Transcript levels of WUS and its target gene in the stem cells, CLAVATA3, are reduced in obe3-2. On the other hand, OBE3 and OBE4 transcripts are both indirectly upregulated by ectopic WUS expression. Our results suggest a positive feedback regulation between WUS and OBE3 that contributes to shoot meristem homeostasis. PMID- 27196374 TI - Sedimentation coefficient distributions of large particles. AB - The spatial and temporal evolution of concentration boundaries in sedimentation velocity analytical ultracentrifugation reports on the size distribution of particles with high hydrodynamic resolution. For large particles such as large protein complexes, fibrils, viral particles, or nanoparticles, sedimentation conditions usually allow migration from diffusion to be neglected relative to sedimentation. In this case, the shape of the sedimentation boundaries of polydisperse mixtures relates directly to the underlying size-distributions. Integral and derivative methods for calculating sedimentation coefficient distributions g*(s) of large particles from experimental boundary profiles have been developed previously, and are recapitulated here in a common theoretical framework. This leads to a previously unrecognized relationship between g*(s) and the time-derivative of concentration profiles. Of closed analytical form, it is analogous to the well-known Bridgman relationship for the radial derivative. It provides a quantitative description of the effect of substituting the time derivative by scan differences with finite time intervals, which appears as a skewed box average of the true distribution. This helps to theoretically clarify the differences between results from time-derivative method and the approach of directly fitting the integral definition of g*(s) to the entirety of experimental boundary data. PMID- 27196375 TI - Association of Physical Activity by Type and Intensity With Digestive System Cancer Risk. AB - IMPORTANCE: Accumulating evidence indicates that common carcinogenic pathways may underlie digestive system cancers. Physical activity may influence these pathways. Yet, to our knowledge, no previous study has evaluated the role of physical activity in overall digestive system cancer risk. OBJECTIVE: To examine the association between physical activity and digestive system cancer risk, accounting for amount, type (aerobic vs resistance), and intensity of physical activity. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study followed 43 479 men from the Health Professionals Follow-up Study from 1986 to 2012. At enrollment, the eligible participants were 40 years or older, were free of cancer, and reported physical activity. Follow-up rates exceeded 90% in each 2 year cycle. EXPOSURES: The amount of total physical activity expressed in metabolic equivalent of task (MET)-hours/week. MAIN OUTCOMES AND MEASURES: Incident cancer of the digestive system encompassing the digestive tract (mouth, throat, esophagus, stomach, small intestine, and colorectum) and digestive accessory organs (pancreas, gallbladder, and liver). RESULTS: Over 686 924 person years, we documented 1370 incident digestive system cancers. Higher levels of physical activity were associated with lower digestive system cancer risk (hazard ratio [HR], 0.74 for >=63.0 vs <=8.9 MET-hours/week; 95% CI, 0.59-0.93; P value for trend = .003). The inverse association was more evident with digestive tract cancers (HR, 0.66 for >=63.0 vs <=8.9 MET-hours/week; 95% CI, 0.51-0.87) than with digestive accessary organ cancers. Aerobic exercise was particularly beneficial against digestive system cancers, with the optimal benefit observed at approximately 30 MET-hours/week (HR, 0.68; 95% CI, 0.56-0.83; P value for nonlinearity = .02). Moreover, as long as the same level of MET-hour score was achieved from aerobic exercise, the magnitude of risk reduction was similar regardless of intensity of aerobic exercise. CONCLUSIONS AND RELEVANCE: Physical activity, as indicated by MET-hours/week, was inversely associated with the risk of digestive system cancers, particularly digestive tract cancers, in men. The optimal benefit was observed through aerobic exercise of any intensity at the equivalent of energy expenditure of approximately 10 hours/week of walking at average pace. Future studies are warranted to confirm our findings and to translate them into clinical and public health recommendation. PMID- 27196376 TI - Effect of Phytoplankton Richness on Phytoplankton Biomass Is Weak Where the Distribution of Herbivores is Patchy. AB - Positive effects of competitor species richness on competitor productivity can be more pronounced at a scale that includes heterogeneity in 'bottom-up' environmental factors, such as the supply of limiting nutrients. The effect of species richness is not well understood in landscapes where variation in 'top down' factors, such as the abundance of predators or herbivores, has a strong influence competitor communities. I asked how phytoplankton species richness directly influenced standing phytoplankton biomass in replicate microcosm regions where one patch had a population of herbivores (Daphnia pulicaria) and one patch did not have herbivores. The effect of phytoplankton richness on standing phytoplankton biomass was positive but weak and not statistically significant at this regional scale. Among no-Daphnia patches, there was a significant positive effect of phytoplankton richness that resulted from positive selection effects for two dominant and productive species in polycultures. Among with-Daphnia patches there was not a significant effect of phytoplankton richness. The same two species dominated species-rich polycultures in no- and with-Daphnia patches but both species were relatively vulnerable to consumption by Daphnia. Consistent with previous studies, this experiment shows a measurable positive influence of primary producer richness on biomass when herbivores were absent. It also shows that given the patchy distribution of herbivores at a regional scale, a regional positive effect was not detected. PMID- 27196377 TI - World Health Organization grade II-III astrocytomas consist of genetically distinct tumor lineages. AB - Recent investigations revealed genetic analysis provides important information in management of gliomas, and we previously reported grade II-III gliomas could be classified into clinically relevant subgroups based on the DNA copy number aberrations (CNAs). To develop more precise genetic subgrouping, we investigated the correlation between CNAs and mutational status of the gene encoding isocitrate dehydrogenase (IDH) of those tumors. We analyzed the IDH status and CNAs of 174 adult supratentorial gliomas of astrocytic or oligodendroglial origin by PCR-based direct sequencing and comparative genomic hybridization, respectively. We analyzed the relationship between genetic subclassification and clinical features. We found the most frequent aberrations in IDH mutant tumors were the combined whole arm-loss of 1p and 19q (1p/19q codeletion) followed by gain on chromosome arm 7q (+7q). The gain of whole chromosome 7 (+7) and loss of 10q (-10q) were detected in IDH wild-type tumors. Kaplan-Meier estimates for progression-free survival showed that the tumors with mutant IDH, -1p/19q, or +7q (in the absence of +7p) survived longer than tumors with wild-type IDH, +7, or 10q. As tumors with +7 (IDH wild-type) showed a more aggressive clinical nature, they are probably not a subtype that developed from the slowly progressive tumors with +7q (IDH mutant). Thus, tumors with a gain on chromosome 7 (mostly astrocytic) comprise multiple lineages, and such differences in their biological nature should be taken into consideration during their clinical management. PMID- 27196380 TI - Comparison of gDNA-based versus mRNA-based KIT D816V mutation analysis reveals large differences between blood and bone marrow in systemic mastocytosis. PMID- 27196379 TI - Use of RNA amplification and electrophoresis for studying virus aerosol collection efficiency and their comparison with plaque assays. AB - The spread of virus-induced infectious diseases through airborne routes of transmission is a global concern for economic and medical reasons. To study virus transmission, it is essential to have an effective aerosol collector such as the growth tube collector (GTC) system that utilizes water-based condensation for collecting virus-containing aerosols. In this work, we characterized the GTC system using bacteriophage MS2 as a surrogate for a small RNA virus. We investigated using RNA extraction and reverse transcription- polymerase chain reaction (RT-PCR) to study the total virus collection efficiency of the GTC system. Plaque assays were also used to enumerate viable viruses collected by the GTC system compared to that by a commercially available apparatus, the SKC(r) Biosampler. The plaque assay counts were used to enumerate viable viruses whereas RT-PCR provides a total virus count, including those viruses inactivated during collection. The effects of relative humidity (RH) and other conditions on collection efficiency were also investigated. Our results suggest that the GTC has a collection efficiency for viable viruses between 0.24 and 1.8% and a total virus collection efficiency between 18.3 and 79.0%, which is 1-2 orders of magnitude higher than that of the SKC(r) Biosampler. Moreover, higher RH significantly increases both the viable and total collection efficiency of the GTC, while its effect on the collection efficiency of the SKC(r) Biosampler is not significant. PMID- 27196378 TI - Loss of control eating and eating disorders in adolescents before bariatric surgery. AB - OBJECTIVE: This study assessed loss of control (LOC) eating and eating disorders (EDs) in adolescents undergoing bariatric surgery for severe obesity. METHOD: Preoperative baseline data from the Teen Longitudinal Assessment of Bariatric Surgery (Teen-LABS) multisite observational study (n = 242; median BMI = 51 kg/m2 ; mean age= 17; 76% female adolescents; 72% Caucasian) included anthropometric and self-report questionnaires, including the Questionnaire of Eating and Weight Patterns-Revised (QEWP-R), the Night Eating Questionnaire (NEQ), the Beck Depression Inventory (BDI-II), and the Impact of Weight on Quality of Life-Kids (IWQOL-Kids) RESULTS: LOC eating (27%) was common and ED diagnoses included binge eating disorder (7%), night eating syndrome (5%), and bulimia nervosa (1%). Compared to those without LOC eating, those with LOC eating reported greater depressive symptomatology and greater impairment in weight-related quality of life. DISCUSSION: Before undergoing bariatric surgery, adolescents with severe obesity present with problematic disordered eating behaviors and meet diagnostic criteria for EDs. LOC eating, in particular, was associated with several negative psychosocial factors. Findings highlight targets for assessment and intervention in adolescents before bariatric surgery. (c) 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2016; 49:947-952). PMID- 27196381 TI - Barber-Say syndrome and Ablepharon-Macrostomia syndrome: An overview. AB - Barber-Say syndrome (BSS) and Ablepharon-Macrostomia syndrome (AMS) are congenital malformation syndromes caused by heterozygous mutations in TWIST2. Here we provide a critical review of all patients published with these syndromes. We excluded several earlier reports due to misdiagnosis or insufficient data for reliable confirmation of the diagnosis. There remain 16 reliably diagnosed individuals with BSS and 16 with AMS. Major facial characteristics present in both entities, albeit often in differing frequencies, are excessive facial creases, hypertelorism, underdevelopment of the anterior part of the eyelids (anterior lamella), ectropion, broad nasal ridge and tip, thick and flaring alae nasi, protruding maxilla, wide mouth, thin upper vermillion, and attached ear lobes. In BSS a remarkable extension of the columella on the philtrum can be seen, and in both the medial parts of the cheeks bulge towards the corners of the mouth (cheek pads). Scalp hair is sparse in AMS only, but sparse eyebrows and eyelashes occur in both entities, and general hypertrichosis occurs in BSS. We compare these characteristics with those in Setleis syndrome which can also be caused by TWIST2 mutations. The resemblance between the three syndromes is considerable, and likely differences seem larger than they actually are due to insufficiently complete evaluation for all characteristics of the three entities in the past. It is likely that with time it can be concluded that BSS. AMS and Setleis syndrome form a continuum. (c) 2016 Wiley Periodicals, Inc. PMID- 27196382 TI - Hybrid Potential Simulation of the Acylation of Enterococcus faecium l,d Transpeptidase by Carbapenems. AB - The l,d-transpeptidases, Ldts, catalyze peptidoglycan cross-linking in beta lactam-resistant mutant strains of several bacteria, including Enterococcus faecium and Mycobacterium tuberculosis. Although unrelated to the essential d,d transpeptidases, which are inactivated by the beta-lactam antibiotics, they are nevertheless inhibited by the carbapenem antibiotics, making them potentially useful targets in the treatment of some important diseases. In this work, we have investigated the acylation mechanism of the Ldt from E. faecium by the carbapenem, ertapenem, using computational techniques. We have employed molecular dynamics simulations in conjunction with QC/MM hybrid potential calculations to map out possible reaction paths. We have focused on determining the following: (i) the protonation state of the nucleophilic cysteine of the enzyme when it attacks; (ii) whether nucleophilic attack and beta-lactam ring-opening are concerted or stepwise, the latter occurring via an oxyanion intermediate; and (iii) the identities of the proton acceptors at the beginning and end of the reaction. Overall, we note that there is considerable plasticity in the mechanisms, owing to the significant flexibility of the enzyme, but find that the preferred pathways are ones in which nucleophilic attack of cysteine thiolate is concerted with beta-lactam ring-opening. PMID- 27196383 TI - Comment on: Clinical Efficacy of Mudpack Therapy in Treating Knee Osteoarthritis: A Meta-analysis of Randomized Controlled Studies. PMID- 27196384 TI - Influence of Cognitive Impairment on Mobility Recovery of Patients With Hip Fracture. AB - OBJECTIVE: The aims of this study were to study the mobility recovery in hip fracture patients and determine the influence of cognitive impairment on mobility within the first 3 months after surgery. DESIGN: This prospective cohort study was carried out in an acute public hospital in southern Spain and included 275 patients, 65 years or older, with a hip fracture. Mobility and Cognitive status were measured by Tinetti Performance-Oriented Mobility Assessment and Pfeiffers' Scale (Short Portable Mental State Questionnaire), respectively. Multiple linear regression was used to examine the influence of cognitive impairment on mobility. RESULTS: The median Performance-Oriented Mobility Assessment score changed from 4 (3-4) points at discharge to 17 (7-22) at 3 months. All degrees of cognitive impairment were negatively associated with gait and balance at 1 and 3 months after surgery (P < 0.01). Age, weight bearing, length of hospital stay, and postsurgical complications were also identified as independent predictors of mobility outcome at 3 months. CONCLUSIONS: Cognitive impairment is a negative prognostic factor for the recovery of mobility in elderly patients with a hip fracture. New treatment strategies are needed for hip fracture patients with cognitive impairment. PMID- 27196385 TI - Water-Cooled Radiofrequency Provides Pain Relief, Decreases Disability, and Improves Quality of Life in Chronic Knee Osteoarthritis. AB - Chronic osteoarthritis (OA) is a widespread source of pain and disability and represents a growing economic burden across aging populations. Representing a major focus of arthritis care, OA of the knee is especially concerning as it has the potential to restrict mobility and significantly impair quality of life. Chronic OA is often poorly managed both pharmacologically and nonpharmacologically, with surgical management representing the definitive treatment. Those who are not surgical candidates or simply opt for minimally invasive treatments are usually faced with a lack of alternatives. An additional treatment presents itself in the form of water-cooled radiofrequency ablation, which involves the use of thermal lesions to interrupt the active pain pathways. An 81-year-old woman with bilateral severe knee OA was initially seen and evaluated in an outpatient physiatry clinic after multiple previous workups of her ongoing knee pain. With a known diagnosis of end-stage knee OA, the patient chose to proceed with bilateral water-cooled radiofrequency ablation. At 6 weeks and 3 months after the procedure, the patient maintained adequate levels of pain relief, markedly improved function, and enhanced quality of life. Water-cooled radiofrequency ablation has the potential to create lasting pain relief and with minimal adverse effects in patients with chronic knee OA. PMID- 27196388 TI - Potentially traumatic events and mental health problems among children of Iraqi refugees: The roles of relationships with parents and feelings about school. AB - This study examined mental health problems among children of Iraqi refugees, most of whom were Christian. Exposure to potentially traumatic events was hypothesized to predict more symptoms of depression and traumatic stress. Moreover, youth reports of supportive relationships with parents and positive feelings about school were examined in relation to mental health problems. These promotive factors were expected to mitigate the hypothesized association between traumatic event exposure and mental health problems. Participants were 211 youth recruited from agencies and programs serving Iraqi refugees in a large metropolitan area in the United States. The hypotheses were partially supported. Youth who reported experiencing more potentially traumatic events endorsed more traumatic stress and depression symptoms. After accounting for exposure to potentially traumatic events and other covariates, youth who reported more positive feelings about school endorsed fewer symptoms of traumatic stress, and youth who reported more supportive relationships with parents endorsed fewer symptoms of depression. In addition, there was an interaction between potentially traumatic events and relationships with parents when predicting depression symptoms. Youth endorsed higher levels of depression symptoms when they reported less supportive relationships, regardless of the amount of traumatic event exposure, whereas youth endorsed lower levels of depression symptoms when they reported more supportive relationships with parents, but only at low levels of traumatic event exposure. Otherwise, the main effects were not qualified by interactions between potentially traumatic event exposure and the promotive factors. The findings from this study have implications for future research, policy, and practice with children of refugees. (PsycINFO Database Record PMID- 27196389 TI - Domestic violence survivors' empowerment and mental health: Exploring the role of the alliance with advocates. AB - Over the last 4 decades, domestic violence (DV) programs-both residential and nonresidential-have sprung up in communities across the country with the aim of helping survivors become safe. These programs place strong emphasis on the relationship between the advocate and survivor as critical to becoming safer and healing from the trauma of abuse. Yet little research has demonstrated the extent to which specific aspects of the advocate-survivor alliance are related to specific indicators of survivor well-being, nor shown what factors might mediate that relationship. This study explored in a sample of help-seeking survivors (N = 370) whether the strength of the alliance between survivors and their advocates is related to lower symptoms of depression and posttraumatic stress disorder (PTSD) and whether this association is mediated by survivors' sense of empowerment in the domain of safety. The structural equation model we tested also controlled for variables that might influence these relationships, including race/ethnicity, financial strain, and length of stay in the program. As expected, stronger alliance was associated with reduced symptoms of both depression and PTSD, through the mechanism of empowerment in the domain safety. These findings provide direction to programs seeking to establish a theory of change and point the way toward longitudinal research on the nature and function of the alliance as a potential contributor to healing. (PsycINFO Database Record PMID- 27196390 TI - Optimizing foster family placement for infants and toddlers: A randomized controlled trial on the effect of the foster family intervention. AB - The relationship between foster children and their foster carers comes with many risks and may be very stressful both for parents and children. We developed an intervention (foster family intervention [FFI]) to tackle these risks. The intervention focuses on foster children below the age of 5 years. The objective was to investigate the effects of FFI on the interactions between foster parents and foster children. A randomized control trial was carried out with a sample of 123 preschool aged children (mean age 18.8 months; 51% boys) and their foster carers. A pretest was carried out 6 to 8 weeks after placement and a posttest one half year later. Interactions were videotaped and coded using the Emotional Availability Scales (EAS). Foster carers were asked to fill in the Dutch version of the Parenting Stress Index. Morning and evening samples of children's salivary cortisol were taken. In the posttest, significantly positive effects were found on the following EAS subscales: Sensitivity, Structuring, Nonintrusiveness, and Responsiveness. We found no significant differences on stress levels of foster carers and children (Nijmeegse Ouderlijke Stress Index domains and salivary cortisol). This study shows that the FFI has a significant positive effect on parenting skills as measured with EAS and on Responsiveness of the foster child. Findings are discussed in terms of impact and significance relating to methodology and design of the study and to clinical relevance. (PsycINFO Database Record PMID- 27196391 TI - Sex and the nursing home. AB - The current article discusses the case of Henry Rahons. A nearly 80 year old man who was accused by the local district attorney of having unlawful sexual contact with Donna, his second wife of some seven years who had developed Alzheimer's disease in her later years. Under Iowa law, he was accused of having sexually abused her because she had "a mental defect or incapacity which precludes giving consent" to sex acts. A jury acquitted Henry of the charge of sexually abusing his wife. The evidence was equivocal that a sex act occurred on May 23, 2014, the date specified in the indictment. This article addresses the ability to assessed competence to consent to sex in similar situations. The current rules and attitudes about senior sex in nursing homes needs to be reevaluated. (PsycINFO Database Record PMID- 27196392 TI - Manipulating the temperature dependence of the thermal conductivity of graphene phononic crystal. AB - By using non-equilibrium molecular dynamics simulations, modulating the temperature dependence of thermal conductivity of graphene phononic crystals (GPnCs) is investigated. It is found that the temperature dependence of thermal conductivity of GPnCs follows ~T (-alpha) behavior. The power exponents (alpha) can be efficiently tuned by changing the characteristic size of GPnCs. The phonon participation ratio spectra and dispersion relation reveal that the long-range phonon modes are more affected in GPnCs with larger holes (L 0). Our results suggest that constructing GPnCs is an effective method to manipulate the temperature dependence of thermal conductivity of graphene, which would be beneficial for developing GPnC-based thermal management and signal processing devices. PMID- 27196393 TI - Differential actinodin1 regulation in zebrafish and mouse appendages. AB - The fin-to-limb transition is an important evolutionary step in the colonization of land and diversification of all terrestrial vertebrates. We previously identified a gene family in zebrafish, termed actinodin, which codes for structural proteins crucial for the formation of actinotrichia, rigid fibrils of the teleost fin. Interestingly, this gene family is absent from all tetrapod genomes examined to date, suggesting that it was lost during limb evolution. To shed light on the disappearance of this gene family, and the consequences on fin to-limb transition, we characterized actinodin regulatory elements. Using fluorescent reporters in transgenic zebrafish, we identified tissue-specific cis acting regulatory elements responsible for actinodin1 (and1) expression in the ectodermal and mesenchymal cell populations of the fins, respectively. Mutagenesis of potential transcription factor binding sites led to the identification of one binding site crucial for and1 expression in ectodermal cells. We show that these regulatory elements are partially functional in mouse limb buds in a tissue-specific manner. Indeed, the zebrafish regulatory elements target expression to the dorsal and ventral ectoderm of mouse limb buds. Absence of expression in the apical ectodermal ridge is observed in both mouse and zebrafish. However, cells of the mouse limb bud mesoderm do not express the transgene, in contrast to zebrafish. Altogether these results hint for a change in regulation of and1 during evolution that led to the downregulation and eventual loss of this gene from tetrapod genomes. PMID- 27196394 TI - Abyss or Shelter? On the Relevance of Web Search Engines' Search Results When People Google for Suicide. AB - Despite evidence that suicide rates can increase after suicides are widely reported in the media, appropriate depictions of suicide in the media can help people to overcome suicidal crises and can thus elicit preventive effects. We argue on the level of individual media users that a similar ambivalence can be postulated for search results on online suicide-related search queries. Importantly, the filter bubble hypothesis (Pariser, 2011) states that search results are biased by algorithms based on a person's previous search behavior. In this study, we investigated whether suicide-related search queries, including either potentially suicide-preventive or -facilitative terms, influence subsequent search results. This might thus protect or harm suicidal Internet users. We utilized a 3 (search history: suicide-related harmful, suicide-related helpful, and suicide-unrelated) * 2 (reactive: clicking the top-most result link and no clicking) experimental design applying agent-based testing. While findings show no influences either of search histories or of reactivity on search results in a subsequent situation, the presentation of a helpline offer raises concerns about possible detrimental algorithmic decision-making: Algorithms "decided" whether or not to present a helpline, and this automated decision, then, followed the agent throughout the rest of the observation period. Implications for policy making and search providers are discussed. PMID- 27196395 TI - Disparate rates of acute rejection and donor-specific antibodies among high immunologic risk renal transplant subgroups receiving antithymocyte globulin induction. AB - Lymphocyte-depleting induction lowers acute rejection (AR) rates among high immunologic risk (HIR) renal transplant recipients, including African Americans (AAs), retransplants, and the sensitized. It is unclear whether different HIR subgroups experience similarly low rates of AR. We aimed to describe the incidence of AR and de novo donor-specific antibody (dnDSA) among HIR recipients categorized by age, race, or donor type. All received antithymocyte globulin (ATG) induction and triple maintenance immunosuppression. A total of 464 HIR recipients from 2007 to 2014 were reviewed. AR and dnDSA rates at 1 year for the entire population were 14% and 27%, respectively. AR ranged from 6.7% among living donor (LD) recipients to 30% in younger AA deceased donor (DD) recipients. De novo donor-specific antibody at 1 year ranged from 7% in older non-AA LD recipients to 32% in AAs. AA race remained as an independent risk factor for AR among DD recipients and for dnDSA among all HIR recipients. Development of both AR and dnDSA within the first year was associated with a 54% graft survival at 5 years and was an independent risk factor for graft loss. Despite utilization of recommended immunosuppression for HIR recipients, substantial disparities exist among subgroups, warranting further consideration of individualized immunosuppression in certain HIR subgroups. PMID- 27196397 TI - Does dorsal capsule interposition improve the results of proximal row carpectomy in Kienbock's disease? One year randomized trial. AB - INTRODUCTION: Proximal row carpectomy (PRC) is an option as a salvage procedure in late stage Kienbock's disease. In this study, we hypothesize that interposition of a dorsal capsular flap following PRC improves functional outcomes. No comparative study is available to assess whether interposition is effective from the functional perspective. This study aims to determine whether the addition of this procedure may improve functional outcomes at a one year assessment. METHODS: Thirty adult patients with IIIA and IIIB Lichtman stages, aged 18-54 years, were randomized into two study groups. Fourteen patients were allocated to the "no interposition group" and 16 to the "interposition" group. DASH questionnaire was used to evaluate quality of life. Cooney's system was used to assess pain, functional state, range of motion, and grip strength. Complications were also assessed. Final followup and clinical assessment occurred after 12 months. RESULTS: After 12 months and no patient losses, outcomes were similar in both groups. DASH scores (41.9 (7.5) vs. 42.9 (12.8), p = 0.79)), Cooney's system (poor results, 0.6 vs. 0.14, p = 0.54), and complications were similar between groups. In conclusion, the inclusion of a dorsal capsular flap does not improve functional outcomes in PRC. Low rates of complications were found in both groups. PMID- 27196396 TI - OFD1, as a Ciliary Protein, Exhibits Neuroprotective Function in Photoreceptor Degeneration Models. AB - Ofd1 is a newly identified causative gene for Retinitis pigmentosa (RP), a photoreceptor degenerative disease. This study aimed to examine Ofd1 localization in retina and further to investigate its function in photoreceptor degeneration models. Ofd1 localization in rat retina was examined using immunofluorescence. N methyl-N-nitrosourea (MNU)-induced rats and Royal College of Surgeons (RCS) rats were used as photoreceptor degeneration models. The expression pattern of Ofd1, other ciliary associated genes and Wnt signaling pathway genes were examined in rat models. Furthermore, pEGFP-Ofd1-CDS and pSUPER-Ofd1-shRNA were constructed to overexpress and knockdown the expression level in 661W and R28 cells. MNU was also used to induce cell death. Cilia formation was observed using immunocytochemistry (ICC). Reactive oxygen species (ROS) were detected using the 2', 7'-Dichlorofluorescin diacetate (DCFH-DA) assay. Apoptosis genes expression was examined using qRT-PCR, Western blotting and fluorescence-activated cell sorting (FACS). Ofd1 localized to outer segments of rat retina photoreceptors. Ofd1 and other ciliary proteins expression levels increased from the 1st and 4th postnatal weeks and decreased until the 6th week in the RCS rats, while their expression consistently decreased from the 1st and 7th day in the MNU rats. Moreover, Wnt signaling pathway proteins expression was significantly up regulated in both rat models. Knockdown of Ofd1 expression resulted in a smaller population, shorter length of cell cilia, and lower cell viability. Ofd1 overexpression partially attenuated MNU toxic effects by reducing ROS levels and mitigating apoptosis. To the best of our knowledge, this is the first study demonstrating Ofd1 localization and its function in rat retina and in retinal degeneration rat models. Ofd1 plays a role in controlling photoreceptor cilium length and number. Importantly, it demonstrates a neuroprotective function by protecting the photoreceptor from oxidative stress and apoptosis. These data have expanded our understanding of Ofd1 function beyond cilia, and we concluded that ofd1 neuroprotection could be a potential treatment strategy in retina degeneration models. PMID- 27196401 TI - Simultaneous Bioreduction of Multiple Oxidized Contaminants Using a Membrane Biofilm Reactor. AB - This study tests a hydrogen-based membrane biofilm reactor (MBfR) to investigate simultaneous bioreduction of selected oxidized contaminants, including nitrate (-N), sulfate (), bromate (), chromate (Cr(VI)) and para-chloronitrobenzene (p CNB). The experiments demonstrate that MBfR can achieve high performance for contaminants bioreduction to harmless or immobile forms in 240 days, with a maximum reduction fluxes of 0.901 g -N/m2.d, 1.573 g /m2.d, 0.009 g /m2.d, 0.022 g Cr(VI)/m2.d, and 0.043 g p-CNB/m2.d. Increasing H2 pressure and decreasing influent surface loading enhanced removal efficiency of the reactor. Flux analysis indicates that nitrate and sulfate reductions competed more strongly than , Cr(VI) and p-CNB reduction. The average H2 utilization rate, H2 flux, and H2 utilization efficiency of the reactor were 0.026 to 0.052 mg H2/cm3.d, 0.024 to 0.046 mg H2/cm2.d, and 97.5% to 99.3% (nearly 100%). Results show the hydrogen-based MBfR may be suitable for removing multiple oxidized contaminants in drinking water or groundwater. PMID- 27196399 TI - The decisionalization of individualization. AB - Throughout forensic science and adjacent branches, academic researchers and practitioners continue to diverge in their perception and understanding of the notion of 'individualization', that is the claim to reduce a pool of potential donors of a forensic trace to a single source. In particular, recent shifts to refer to the practice of individualization as a decision have been revealed as being a mere change of label [1], leaving fundamental changes in thought and understanding still pending. What is more, professional associations and practitioners shy away from embracing the notion of decision in terms of the formal theory of decision in which individualization may be framed, mainly because of difficulties to deal with the measurement of desirability or undesirability of the consequences of decisions (e.g., using utility functions). Building on existing research in the area, this paper presents and discusses fundamental concepts of utilities and losses with particular reference to their application to forensic individualization. The paper emphasizes that a proper appreciation of decision tools not only reduces the number of individual assignments that the application of decision theory requires, but also shows how such assignments can be meaningfully related to constituting features of the real world decision problem to which the theory is applied. It is argued that the decisonalization of individualization requires such fundamental insight to initiate changes in the fields' underlying understandings, not merely in their label. PMID- 27196398 TI - Prevalence of Doctor-Diagnosed Arthritis at State and County Levels - United States, 2014. AB - Doctor-diagnosed arthritis is a common chronic condition that affects approximately 52.5 million (22.7%) adults in the United States and is a leading cause of disability (1,2). The prevalence of doctor-diagnosed arthritis has been well documented at the national level (1), but little has been published at the state level and the county level, where interventions are carried out and can have their greatest effect. To estimate the prevalence of doctor-diagnosed arthritis among adults at the state and county levels, CDC analyzed data from the 2014 Behavioral Risk Factor Surveillance System (BRFSS). This report summarizes the results of that analysis, which found that, for all 50 states and the District of Columbia (DC) overall, the age-standardized median prevalence of doctor-diagnosed arthritis was 24% (range = 18.8%-35.5%). The age-standardized model-predicted prevalence of doctor-diagnosed arthritis varied substantially by county, with estimates ranging from 15.8% to 38.6%. The high prevalence of arthritis in all counties, and the high frequency of arthritis-attributable limitations (1) among adults with arthritis, suggests that states and counties might benefit from expanding underused, evidence-based interventions for arthritis that can reduce arthritis symptoms and improve self-management. PMID- 27196405 TI - Bronchoscopy in lung cancer: navigational modalities and their clinical use. AB - INTRODUCTION: More than 150,000 solitary pulmonary nodules are reported each year in the United States. As the popularity of low dose CT scan use for screening grows, these numbers are likely to increase substantially over the coming years. More than 10 million CT scans of the chest were performed in the United States alone in 2012, highlighting the potential for this clinical scenario. Detecting a nodule on either a chest radiograph or a CT scan frequently leads to a cascade of further investigations to establish a definite diagnosis. Thoracic surgery is frequently performed to obtain a tissue diagnosis in these cases, however, for what often turns out to be a benign abnormality. AREAS COVERED: During the last decade, several new technologies have been introduced to the field of bronchoscopy. As experience with these technologies has increased, the body of published literature has grown. Expert commentary: In this review, we assess the most important and interesting articles in the field. The value and the limitations of the various options will be discussed based on the actual evidence. PMID- 27196406 TI - Characterization of Five Novel Mitoviruses in the White Pine Blister Rust Fungus Cronartium ribicola. AB - The white pine blister rust (WPBR) fungus Cronartium ribicola (J.C. Fisch.) is an exotic invasive forest pathogen causing severe stem canker disease of native white pine trees (subgenus Strobus) in North America. The present study reports discovery of five novel mitoviruses in C. ribicola by deep RNA sequencing. The complete genome of each mitovirus was determined by rapid amplification of cDNA ends (RACE) and reverse transcriptase-polymerase chain reaction (RT-PCR). A single open reading frame (ORF) encoding a putative RNA-dependent RNA polymerase (RdRp) was detected in each of the viral genomes using mitochondrial genetic codes. Phylogenetic analysis indicated that the C. ribicola mitoviruses (CrMV1 to CrMV5) are new putative species of the genus Mitovirus. qRT-PCR and RNA-Seq analyses revealed that viral RNAs were significantly increased in fungal mycelia in cankered pine stems compared to expression during two different stages of spore development, suggesting that viral genome replication and transcription benefit from active growth of the host fungus. CrMVs were widespread with relatively high levels of minor allele frequency (MAF) in western North America. As the first report of mitoviruses in the Class Pucciniomycetes, this work allows further investigation of the dynamics of a viral community in the WPBR pathosystem, including potential impacts that may affect pathogenicity and virulence of the host fungus. PMID- 27196416 TI - Early Stress History Alters Serum Insulin-Like Growth Factor-1 and Impairs Muscle Mitochondrial Function in Adult Male Rats. AB - Early-life adversity is associated with an enhanced risk for adult psychopathology. Psychiatric disorders such as depression exhibit comorbidity for metabolic dysfunction, including obesity and diabetes. However, it is poorly understood whether, besides altering anxiety and depression-like behaviour, early stress also evokes dysregulation of metabolic pathways and enhances vulnerability for metabolic disorders. We used the rodent model of the early stress of maternal separation (ES) to examine the effects of early stress on serum metabolites, insulin-like growth factor (IGF)-1 signalling, and muscle mitochondrial content. Adult ES animals exhibited dyslipidaemia, decreased serum IGF1 levels, increased expression of liver IGF binding proteins, and a decline in the expression of specific metabolic genes in the liver and muscle, including Pck1, Lpl, Pdk4 and Hmox1. These changes occurred in the absence of alterations in body weight, food intake, glucose tolerance, insulin tolerance or insulin levels. ES animals also exhibited a decline in markers of muscle mitochondrial content, such as mitochondrial DNA levels and expression of TFAM (transcription factor A, mitochondrial). Furthermore, the expression of several genes involved in mitochondrial function, such as Ppargc1a, Nrf1, Tfam, Cat, Sesn3 and Ucp3, was reduced in skeletal muscle. Adult-onset chronic unpredictable stress resulted in overlapping and distinct consequences from ES, including increased circulating triglyceride levels, and a decline in the expression of specific metabolic genes in the liver and muscle, with no change in the expression of genes involved in muscle mitochondrial function. Taken together, our results indicate that a history of early adversity can evoke persistent changes in circulating IGF-1 and muscle mitochondrial function and content, which could serve to enhance predisposition for metabolic dysfunction in adulthood. PMID- 27196407 TI - Hybrid procedure for total laryngectomy with a flexible robot-assisted surgical system. AB - INTRODUCTION: Total laryngectomy is a standard procedure in head-and-neck surgery for the treatment of cancer patients. Recent clinical experiences have indicated a clinical benefit for patients undergoing transoral robot-assisted total laryngectomy (TORS-TL) with commercially available systems. Here, a new hybrid procedure for total laryngectomy is presented. METHODS: TORS-TL was performed in human cadavers (n = 3) using a transoral-transcervical hybrid procedure. The transoral approach was performed with a robotic flexible robot-assisted surgical system (Flex(r)) and compatible flexible instruments. Transoral access and visualization of anatomical landmarks were studied in detail. RESULTS: Total laryngectomy is feasible with a combined transoral-transcervical approach using the flexible robot-assisted surgical system. Transoral visualization of all anatomical structures is sufficient. The flexible design of the robot is advantageous for transoral surgery of the laryngeal structures. CONCLUSION: Transoral robot assisted surgery has the potential to reduce morbidity, hospital time and fistula rates in a selected group of patients. Initial clinical studies and further development of supplemental tools are in progress. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27196418 TI - Language learning, socioeconomic status, and child-directed speech. AB - Young children's language experiences and language outcomes are highly variable. Research in recent decades has focused on understanding the extent to which family socioeconomic status (SES) relates to parents' language input to their children and, subsequently, children's language learning. Here, we first review research demonstrating differences in the quantity and quality of language that children hear across low-, mid-, and high-SES groups, but also-and perhaps more importantly-research showing that differences in input and learning also exist within SES groups. Second, in order to better understand the defining features of 'high-quality' input, we highlight findings from laboratory studies examining specific characteristics of the sounds, words, sentences, and social contexts of child-directed speech (CDS) that influence children's learning. Finally, after narrowing in on these particular features of CDS, we broaden our discussion by considering family and community factors that may constrain parents' ability to participate in high-quality interactions with their young children. A unification of research on SES and CDS will facilitate a more complete understanding of the specific means by which input shapes learning, as well as generate ideas for crafting policies and programs designed to promote children's language outcomes. WIREs Cogn Sci 2016, 7:264-275. doi: 10.1002/wcs.1393 For further resources related to this article, please visit the WIREs website. PMID- 27196402 TI - The Comparison of MTT and CVS Assays for the Assessment of Anticancer Agent Interactions. AB - Multiple in vitro tests are widely applied to assess the anticancer activity of new compounds, including their combinations and interactions with other drugs. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay is one of the most commonly used assays to assess the efficacy and interactions of anticancer agents. However, it can be significantly influenced by compounds that modify cell metabolism and reaction conditions. Therefore, several assays are sometimes used to screen for potential anticancer drugs. However, the majority of drug interactions are evaluated only with this single method. The aim of our studies was to verify whether the choice of an assay has an impact on determining the type of interaction and to identify the source of discrepancies. We compared the accuracy of MTT and CVS (crystal violet staining) assays in the interaction of two compounds characterized by similar anticancer activity: isothiocyanates (ITCs) and Selol. Confocal microscopy studies were carried out to assess the influence of these compounds on the reactive oxygen species (ROS) level, mitochondrial membrane potential, dead-to-live cell ratio and MTT-tetrazolium salt reduction rate. The MTT assay was less reliable than CVS. The MTT test of Selol and 2-oxoheptyl ITC, which affected the ROS level and MTT reduction rate, gave false negative (2-oxoheptyl ITC) or false positive (Selol) results. As a consequence, the MTT assay identified an antagonistic interaction between Selol and ITC, while the metabolism-independent CVS test identified an additive or synergistic interaction. In this paper, we show for the first time that the test assay may change the interpretation of the compound interaction. Therefore, the test method should be chosen with caution, considering the mechanism of action of the compound. PMID- 27196417 TI - Penalized Multi-Way Partial Least Squares for Smooth Trajectory Decoding from Electrocorticographic (ECoG) Recording. AB - In the current paper the decoding algorithms for motor-related BCI systems for continuous upper limb trajectory prediction are considered. Two methods for the smooth prediction, namely Sobolev and Polynomial Penalized Multi-Way Partial Least Squares (PLS) regressions, are proposed. The methods are compared to the Multi-Way Partial Least Squares and Kalman Filter approaches. The comparison demonstrated that the proposed methods combined the prediction accuracy of the algorithms of the PLS family and trajectory smoothness of the Kalman Filter. In addition, the prediction delay is significantly lower for the proposed algorithms than for the Kalman Filter approach. The proposed methods could be applied in a wide range of applications beyond neuroscience. PMID- 27196400 TI - Cancer Incidence among Heart, Kidney, and Liver Transplant Recipients in Taiwan. AB - Population-based evidence of the relative risk of cancer among heart, kidney, and liver transplant recipients from Asia is lacking. The Taiwan National Health Insurance Research Database was used to conduct a population-based cohort study of transplant recipients (n = 5396), comprising 801 heart, 2847 kidney, and 1748 liver transplant recipients between 2001 and 2012. Standardized incidence ratios and Cox regression models were used. Compared with the general population, the risk of cancer increased 3.8-fold after heart transplantation, 4.1-fold after kidney transplantation and 4.6-fold after liver transplantation. Cancer occurrence showed considerable variation according to transplanted organs. The most common cancers in all transplant patients were cancers of the head and neck, liver, bladder, and kidney and non-Hodgkin lymphoma. Male recipients had an increased risk of cancers of the head and neck and liver, and female kidney recipients had a significant risk of bladder and kidney cancer. The adjusted hazard ratio for any cancer in all recipients was higher in liver transplant recipients compared with that in heart transplant recipients (hazard ratio = 1.5, P = .04). Cancer occurrence varied considerably and posttransplant cancer screening should be performed routinely according to transplanted organ and sex. PMID- 27196421 TI - Histological Effects of Er:YAG Laser Irradiation with Snoring Handpiece in the Rat Soft Palate. AB - OBJECTIVE: The aim of this study was to assess the effects of laser irradiation with a novel snoring handpiece on the histological structures of the soft palate in a rat model. BACKGROUND: Snoring is a common problem and studies have shown that 20-50% of the population is affected. An apnea-hypopnea index of <5/h without daytime somnolence is documented as simple snoring. No snoring treatment should ever be attempted until a sleep study has been completed to rule out sleep apnea. METHODS: Twenty adult Wistar rats, weighing 200-250 g, were used in this study. Rats were randomized into two groups: experimental group (n = 10) and control group (n = 10). Laser energy was delivered in a horizontal direction to the surface of the soft palate of each rat in the experimental group for 2 min with an Er:YAG laser (LightWalker AT; Fotona) with snoring handpiece (PS04) in a noncontact mode (1.15 W, 2 Hz, 1.5 J/cm(2)). The animals were sacrificed after 24 h, 1 week, 3 weeks, or 5 weeks. The soft palate of each rat was removed by excisional biopsy. The specimens underwent histological examination. Contractions and fibrosis were reported as grading from 1+ to 3+, while edema and hyperemia were evaluated according to the absence (0) or presence (1) of any changes. Statistical analysis was done with the Mann-Whitney U and Spearman's rho tests. RESULT: A noticeable contraction of the soft palate occurred immediately after laser application. Inflammatory changes were observed histologically at 3 weeks postoperatively. Keratinization appeared after the procedure in both groups and decreased gradually. Statistically, there was a strong correlation among inflammation and time and also keratinization and time (p < 0.05). CONCLUSIONS: The present study indicates that Er:YAG laser irradiation with snoring handpiece (PS04) causes acute shrinkage of the mucosa. This contraction decreases gradually but is still present at the end of fifth week. PMID- 27196420 TI - Comparison of a New In-House and Three Published HLA-B*15:02 Screening Methods for Prevention of Carbamazepine-Induced Severe Drug Reactions. AB - Currently, there are three published HLA-B*15:02 screening methods for prevention of carbamazepine-induced severe drug reactions in Asian populations. To analyze available HLA-B*15:02 screening methods, we compared four screening methods, including a multiplex PCR method, a nested PCR method, a LAMP method and our new in-house PCR-dot blot hybridization method. These methods were reviewed regarding their sensitivity, specificity, false positivity and technical considerations. Possible false positive (FP) alleles and genotypes were checked regarding the primers and probes designs, using the IMGT/HLA database. Expected FP rates in Asian populations were predicted using the Allele Frequencies Net Database. All methods had a sensitivity of more than 99.9%, although giving FP results to certain very rare alleles and genotypes. The multiplex PCR method was the only test that gave FP results to certain genotypes of HLA-B*15:13, the allele which is prevalent in Southeast Asian populations. In conclusion, the nested PCR, LAMP and our in-house methods could be applied in various Asian populations, but the multiplex PCR, or any test with FP to HLA-B*15:13, should be applied with caution in the Southeast Asian populations. PMID- 27196419 TI - Health Disparities by Type of Disability: Health Examination Results of Adults (18-64 Years) with Disabilities in Shanghai, China. AB - AIMS: There have been few studies on the disparities within the population with disabilities, especially in China. The aim of this study was to evaluate the differences in some health conditions among people with different types of disabilities in Shanghai. METHODS: This study was conducted using data from the Shanghai Disabled Persons' Rehabilitation Comprehensive Information Platform. The records of 31,082 persons with disabilities who had undergone professional health examination were analyzed, and the prevalence and number of five diseases and five risk factors were examined. Logistic regression was used to explore disparities from two perspectives: 1) basic differences, unadjusted for other factors, and 2) differences after adjusting for key demographic covariates. A p value < 0.05 was considered significant. RESULTS: Individuals with visual disability had a high rate of refractive error (60.0%), and averaged 1.75 diseases of interest, which was the highest value among all disability types. The mean number of risk factors we measured was greatest (1.96) in the population with mental disability. There were significant differences (p < 0.05) between the hearing and speech impairment group and the other groups with respect to most health outcomes, except chronic pharyngitis, hepatic cysts, and high blood pressure. CONCLUSION: Significant differences of selected health outcomes between groups with different types of disabilities remained after controlling for key demographic indicators. Further research is needed to explore the relationships between health conditions and disability types. PMID- 27196422 TI - Measuring Spatial Dependence for Infectious Disease Epidemiology. AB - Global spatial clustering is the tendency of points, here cases of infectious disease, to occur closer together than expected by chance. The extent of global clustering can provide a window into the spatial scale of disease transmission, thereby providing insights into the mechanism of spread, and informing optimal surveillance and control. Here the authors present an interpretable measure of spatial clustering, tau, which can be understood as a measure of relative risk. When biological or temporal information can be used to identify sets of potentially linked and likely unlinked cases, this measure can be estimated without knowledge of the underlying population distribution. The greater our ability to distinguish closely related (i.e., separated by few generations of transmission) from more distantly related cases, the more closely tau will track the true scale of transmission. The authors illustrate this approach using examples from the analyses of HIV, dengue and measles, and provide an R package implementing the methods described. The statistic presented, and measures of global clustering in general, can be powerful tools for analysis of spatially resolved data on infectious diseases. PMID- 27196424 TI - Scalable and Environmentally Benign Process for Smart Textile Nanofinishing. AB - A major challenge in nanotechnology is that of determining how to introduce green and sustainable principles when assembling individual nanoscale elements to create working devices. For instance, textile nanofinishing is restricted by the many constraints of traditional pad-dry-cure processes, such as the use of costly chemical precursors to produce nanoparticles (NPs), the high liquid and energy consumption, the production of harmful liquid wastes, and multistep batch operations. By integrating low-cost, scalable, and environmentally benign aerosol processes of the type proposed here into textile nanofinishing, these constraints can be circumvented while leading to a new class of fabrics. The proposed one step textile nanofinishing process relies on the diffusional deposition of aerosol NPs onto textile fibers. As proof of this concept, we deposit Ag NPs onto a range of textiles and assess their antimicrobial properties for two strains of bacteria (i.e., Staphylococcus aureus and Klebsiella pneumoniae). The measurements show that the logarithmic reduction in bacterial count can get as high as ca. 5.5 (corresponding to a reduction efficiency of 99.96%) when the Ag loading is 1 order of magnitude less (10 ppm; i.e., 10 mg Ag NPs per kg of textile) than that of textiles treated by traditional wet-routes. The antimicrobial activity does not increase in proportion to the Ag content above 10 ppm as a consequence of a "saturation" effect. Such low NP loadings on antimicrobial textiles minimizes the risk to human health (during textile use) and to the ecosystem (after textile disposal), as well as it reduces potential changes in color and texture of the resulting textile products. After three washes, the release of Ag is in the order of 1 wt %, which is comparable to textiles nanofinished with wet routes using binders. Interestingly, the washed textiles exhibit almost no reduction in antimicrobial activity, much as those of as-deposited samples. Considering that a realm of functional textiles can be nanofinished by aerosol NP deposition, our results demonstrate that the proposed approach, which is universal and sustainable, can potentially lead to a wide number of applications. PMID- 27196423 TI - Mass Balance Assessment for Six Neonicotinoid Insecticides During Conventional Wastewater and Wetland Treatment: Nationwide Reconnaissance in United States Wastewater. AB - Occurrence and removal of six high-production high-volume neonicotinoids was investigated in 13 conventional wastewater treatment plants (WWTPs) and one engineered wetland. Flow-weighted daily composites were analyzed by isotope dilution liquid chromatography tandem mass spectrometry, revealing the occurrence of imidacloprid, acetamiprid, and clothianidin at ng/L concentrations in WWTP influent (60.5 +/- 40.0; 2.9 +/- 1.9; 149.7 +/- 289.5, respectively) and effluent (58.5 +/- 29.1; 2.3 +/- 1.4; 70.2 +/- 121.8, respectively). A mass balance showed insignificant removal of imidacloprid (p = 0.09, CI = 95%) and limited removal of the sum of acetamiprid and its degradate, acetamiprid-N-desmethyl (18 +/- 4%, p = 0.01, CI = 95%). Clothianidin was found only intermittently, whereas thiamethoxam, thiacloprid, and dinotefuran were never detected. In the wetland, no removal of imidacloprid or acetamiprid was observed. Extrapolation of data from 13 WWTPs to the nation as a whole suggests annual discharges on the order of 1000-3400 kg/y of imidacloprid contained in treated effluent to surface waters nationwide. This first mass balance and first United States nationwide wastewater reconnaissance identified imidacloprid, acetamiprid, and clothianidin as recalcitrant sewage constituents that persist through wastewater treatment to enter water bodies at significant loadings, potentially harmful to sensitive aquatic invertebrates. PMID- 27196426 TI - Retraction: How the Malaria Vector Anopheles gambiae Adapts to the Use of Insecticide-Treated Nets by African Populations. PMID- 27196425 TI - Effects of High-Temperature-Pressure Polymerized Resin-Infiltrated Ceramic Networks on Oral Stem Cells. AB - OBJECTIVES: The development of CAD-CAM techniques called for new materials suited to this technique and offering a safe and sustainable clinical implementation. The infiltration of resin in a ceramic network under high pressure and high temperature defines a new class of hybrid materials, namely polymer infiltrated ceramics network (PICN), for this purpose which requires to be evaluated biologically. We used oral stem cells (gingival and pulpal) as an in vitro experimental model. METHODS: Four biomaterials were grinded, immersed in a culture medium and deposed on stem cells from dental pulp (DPSC) and gingiva (GSC): Enamic (VITA(r)), Experimental Hybrid Material (EHM), EHM with initiator (EHMi) and polymerized Z100TM composite material (3M(r)). After 7 days of incubation; viability, apoptosis, proliferation, cytoskeleton, inflammatory response and morphology were evaluated in vitro. RESULTS: Proliferation was insignificantly delayed by all the tested materials. Significant cytotoxicity was observed in presence of resin based composites (MTT assay), however no detectable apoptosis and some dead cells were detected like in PICN materials. Cell morphology, major cytoskeleton and extracellular matrix components were not altered. An intimate contact appeared between the materials and cells. CLINICAL SIGNIFICANCE: The three new tested biomaterials did not exhibit adverse effects on oral stem cells in our experimental conditions and may be an interesting alternative to ceramics or composite based CAD-CAM blocks. PMID- 27196428 TI - Slit-Like Deformation of the Coronary Sinus Orifice due to Compression of the Inferior Pyramidal Space by the Severely Dilated Left Ventricle. AB - The coronary sinus is located within the inferior pyramidal space, which is the part of the epicardial visceral fibroadipose tissue wedging between the four cardiac chambers from the bottom of the heart. Therefore, this region is susceptible to the morphological changes of the cardiac chambers. We present a case of slit-like deformation of the coronary sinus orifice due to compression of the inferior pyramidal space by the severely dilated left ventricle, which has not been previously described. PMID- 27196427 TI - Ontogeny and Molecular Phylogeny of Apoamphisiella vernalis Reveal Unclear Separation between Genera Apoamphisiella and Paraurostyla (Protozoa, Ciliophora, Hypotricha). AB - Morphology and divisional morphogenesis of the hypotrich ciliate Apoamphisiella vernalis are investigated based on two populations from Brazil. Typical specimens of A. vernalis replicates its ventral ciliature from six fronto-ventral transverse (FVT) anlagen independently formed for proter and opisthe, plus one or more short anlagen located between IV and V, which form surplus transverse cirri. Dorsal morphogenesis occurs as in typical oxytrichid dorsomarginalians, viz., with formation of three anlagen and fragmentation of the rightmost one. Dorsomarginal kineties are formed near anterior end of right marginal cirral row anlagen. Various anomalous specimens exhibiting more than two long ventral rows were found, which are explained by increasing the number of FVT anlagen and/or the number of cirri produced by anlagen. Comparative ontogeny and phylogenetic analyses based on the 18S rDNA reveal that Apoamphisiella vernalis is closely affine to North American and European strains of the Paraurostyla weissei complex. Their reduced genetic distances and conspicuous morphological variability show that both genera can overlap, which implies the necessity of re evaluating the contextual relevance of some morphological characters commonly used for genus-level separation within hypotrich taxa. PMID- 27196429 TI - Old-School Chemotherapy in Immunotherapeutic Combination in Cancer, A Low-cost Drug Repurposed. AB - Cancer immunotherapy has proven to be a potent treatment modality. Although often successful in generating antitumor immune responses, cancer immunotherapy is frequently hindered by tumor immune-escape mechanisms. Among immunosuppressive strategies within the tumor microenvironment, suppressive immune regulatory cells play a key role in promoting tumor progression through inhibiting the effector arm of the immune response. Targeting these suppressive cells can greatly enhance antitumor immune therapies, hence augmenting a highly effective therapeutic antitumor response. Several approaches are being tested to enhance the effector arm of the immune system while simultaneously inhibiting the suppressor arm. Some of these approaches are none other than traditional drugs repurposed as immune modulators. Cyclophosphamide, an old-school chemotherapeutic agent used across a wide range of malignancies, was found to be a potent immune modulator that targets suppressive regulatory immune cells within the tumor microenvironment while enhancing effector cells. Preclinical and clinical findings have confirmed the ability of low doses of cyclophosphamide to selectively deplete regulatory T cells while enhancing effector and memory cytotoxic T cells within the tumor microenvironment. These immune effects translate to suppressed tumor growth and enhanced survival, evidence of antitumor therapeutic efficacy. This article discusses the reincarnation of cyclophosphamide as an immune modulator that augments novel immunotherapeutic approaches. Cancer Immunol Res; 4(5); 377-82. (c)2016 AACR. PMID- 27196430 TI - Short-term warfarin treatment for apical thrombus in a patient with Takotsubo cardiomyopathy. AB - Takotsubo cardiomyopathy (TCMP) is characterised by a temporary aneurysm of the left ventricular apex in individuals without significant stenosis of the coronary arteries. It is extremely rare to see it combined with a thrombus. In this case report, we present a 57-year-old female patient with TCMP in whom apical thrombus was treated with short-term warfarin use. PMID- 27196431 TI - Programmatic Use of Molecular Xenomonitoring at the Level of Evaluation Units to Assess Persistence of Lymphatic Filariasis in Sri Lanka. AB - BACKGROUND: Sri Lanka's Anti Filariasis Campaign distributed 5 rounds of mass drug administration (MDA with DEC plus albendazole) to all endemic regions in the country from 2002-2006. Post-MDA surveillance results have generally been encouraging. However, recent studies have documented low level persistence of Wuchereria bancrofti in Galle district based on comprehensive surveys that include molecular xenomonitoring (MX, detection of filarial DNA in mosquitoes) results. The purposes of this study were to demonstrate the use of MX in large evaluation units (EUs) and to field test different mosquito sampling schemes. METHODOLOGY/PRINCIPAL FINDINGS: Galle district (population 1.1 million) was divided into two EUs. These included a coastal EU with known persistent LF and an inland EU with little persistent LF. Mosquitoes were systematically sampled from ~300 trap locations in 30 randomly selected clusters (health administrative units) per EU. Approximately 28,000 Culex quinquefasciatus were collected with gravid traps and tested for filarial DNA by qPCR. 92/625 pools (14.7%) from the coastal EU and 8/583 pools (1.4%) from the inland EU were positive for filarial DNA. Maximum likelihood estimates (MLE) for filarial DNA rates were essentially the same when the same number of mosquito pools were collected and tested from 75, 150, or 300 trap sites (range 0.61-0.78% for the coastal EU and 0.04-0.07% for the inland EU). The ability to use a smaller number of trap sites reduces the cost and time required for mosquito sampling. CONCLUSIONS/SIGNIFICANCE: These results suggest there is widespread persistence of W. bancrofti infection in the coastal Galle EU 8 years after the last round of MDA in 2006, and this is consistent with other data from the district. This study has shown that MX can be used by national programs to assess and map the persistence of W. bancrofti at the level of large EUs in areas with Culex transmission. PMID- 27196433 TI - Where to Go: Breaking the Symmetry in Cell Motility. AB - Cell migration in the "correct" direction is pivotal for many biological processes. Although most work is devoted to its molecular mechanisms, the cell's preference for one direction over others, thus overcoming intrinsic random motility, epitomizes a profound principle that underlies all complex systems: the choice of one axis, in structure or motion, from a uniform or symmetric set of options. Explaining directional motility by an external chemo-attractant gradient does not solve but only shifts the problem of causation: whence the gradient? A new study in PLOS Biology shows cell migration in a self-generated gradient, offering an opportunity to take a broader look at the old dualism of extrinsic instruction versus intrinsic symmetry-breaking in cell biology. PMID- 27196432 TI - Blockade of Extracellular ATP Effect by Oxidized ATP Effectively Mitigated Induced Mouse Experimental Autoimmune Uveitis (EAU). AB - Various pathological conditions are accompanied by ATP release from the intracellular to the extracellular compartment. Extracellular ATP (eATP) functions as a signaling molecule by activating purinergic P2 purine receptors. The key P2 receptor involved in inflammation was identified as P2X7R. Recent studies have shown that P2X7R signaling is required to trigger the Th1/Th17 immune response, and oxidized ATP (oxATP) effectively blocks P2X7R activation. In this study we investigated the effect of oxATP on mouse experimental autoimmune uveitis (EAU). Our results demonstrated that induced EAU in B6 mice was almost completely abolished by the administration of small doses of oxATP, and the Th17 response, but not the Th1 response, was significantly weakened in the treated mice. Mechanistic studies showed that the therapeutic effects involve the functional change of a number of immune cells, including dendritic cells (DCs), T cells, and regulatory T cells. OxATP not only directly inhibits the T cell response; it also suppresses T cell activation by altering the function of DCs and Foxp3+ T cell. Our results demonstrated that inhibition of P2X7R activation effectively exempts excessive autoimmune inflammation, which may indicate a possible therapeutic use in the treatment of autoimmune diseases. PMID- 27196434 TI - Association of Extracapsular Spread With Survival According to Human Papillomavirus Status in Oropharynx Squamous Cell Carcinoma and Carcinoma of Unknown Primary Site. AB - IMPORTANCE: The presence of extracapsular spread (ECS) of metastatic nodes is considered a poor prognosticator in head and neck cancer, with postoperative chemoradiation therapy often recommended over radiation therapy alone in such cases. However, there is less clarity regarding the effect of ECS on human papillomavirus-associated oropharynx squamous cell carcinoma (OPSCC) or carcinoma of unknown primary site (CUP). OBJECTIVE: To investigate the association of ECS according to human papillomavirus status in OPSCC and CUP with survival. DESIGN, SETTING, AND PARTICIPANTS: This investigation was a retrospective cohort study performed between August 1998 and March 2015 at an academic teaching hospital. Participants were 83 patients with OPSCC (n = 62) or CUP (n = 21) undergoing neck dissection as part of initial treatment. MAIN OUTCOME AND MEASURES: Human papillomavirus status was determined by p16 immunohistochemistry. The presence of ECS was extrapolated from pathology reports, and the extent of ECS was determined by rereview of original pathology slides. Disease-specific survival (DSS) and recurrence-free survival (RFS) were assessed. RESULTS: Among 83 patients (71 male), there were 45 p16-positive and 38 p16-negative tumors. Fifty-one patients had ECS, which was graded as extensive in 43 cases. The median follow-up was 31 months for all patients and 50 months for surviving patients. Among the entire cohort, adverse predictors of RFS were p16-negative status (hazard ratio [HR], 9.4; 95% CI, 3.3-27.2) and ECS (HR, 6.5; 95% CI, 2.0-21.6). Adverse predictors of DSS were p16-negative status (HR, 16.8; 95% CI, 3.9-71.2) and ECS (HR, 8.3; 95% CI, 2.0-35.3). Among p16-negative patients, ECS was significantly associated with worse RFS (HR, 9.7; 95% CI, 1.3-72.3) and DSS (HR, 8.7; 95% CI, 1.1-62.7). In contrast, among p16-positive patients, ECS had no effect on RFS (HR, 1.1; 95% CI, 0.2-7.8) or DSS (HR, 1.2; 95% CI, 0.1-18.7). CONCLUSIONS AND RELEVANCE: The presence of ECS appears to be associated with survival in OPSCC and CUP according to p16 status. Our findings raise questions regarding the benefits of postoperative chemoradiation therapy in p16-positive patients with ECS. PMID- 27196435 TI - Molybdenum Disulfide as a Protection Layer and Catalyst for Gallium Indium Phosphide Solar Water Splitting Photocathodes. AB - Gallium indium phosphide (GaInP2) is a semiconductor with promising optical and electronic properties for solar water splitting, but its surface stability is problematic as it undergoes significant chemical and electrochemical corrosion in aqueous electrolytes. Molybdenum disulfide (MoS2) nanomaterials are promising to both protect GaInP2 and to improve catalysis because MoS2 is resistant to corrosion and also possesses high activity for the hydrogen evolution reaction (HER). In this work, we demonstrate that GaInP2 photocathodes coated with thin MoS2 surface protecting layers exhibit excellent activity and stability for solar hydrogen production, with no loss in performance (photocurrent onset potential, fill factor, and light-limited current density) after 60 h of operation. This represents a 500-fold increase in stability compared to bare p-GaInP2 samples tested in identical conditions. PMID- 27196436 TI - Modeling the cognitive mechanisms linking autism symptoms and anxiety in adults. AB - Emotional acceptance, alexithymia, and intolerance of uncertainty (IU) contribute to anxiety disorders in neurotypical populations. Their association with anxiety in people diagnosed with autism spectrum disorder (ASD) has not been studied. We aimed to model the contributions of these constructs on the relationship between dimensional measures of autism and anxiety. Participants were 151 adults recruited from 2 sites, including those diagnosed with ASD (n = 76) and a matched comparison group (n = 75). All participants completed a battery of questionnaires measuring core autism symptoms, anxiety, emotional acceptance, alexithymia, and intolerance of uncertainty. Structural equation modeling with mediation was used to examine directional relationships among these variables. Autism symptoms directly predicted less emotional acceptance and increased alexithymia and IU. Alexithymia and acceptance were shown to explain 64% of the effect between autism symptom severity and anxiety level. This suggests that people with ASD experience increased levels of anxiety because they are more likely to react aversively to their emotional experiences, while lacking the ability to identify and understand their emotions. Developing and implementing mindfulness-based interventions aimed at assuaging alexithymia and IU, while increasing emotional acceptance, may be especially helpful in treating anxiety in ASD. (PsycINFO Database Record PMID- 27196438 TI - Fast Knoevenagel Condensations Catalyzed by an Artificial Schiff-Base-Forming Enzyme. AB - The simple catalytic motifs utilized by enzymes created by computational design and directed evolution constitute a potentially valuable source of chemical promiscuity. Here we show that the artificial retro-aldolase RA95.5-8 is able to use a reactive lysine in a hydrophobic pocket to accelerate promiscuous Knoevenagel condensations of electron-rich aldehydes and activated methylene donors. Optimization of this activity by directed evolution afforded an efficient enzyme variant with a catalytic proficiency of 5 * 10(11) M(-1) and a >10(8)-fold catalytic advantage over simple primary and secondary amines. Divergent evolution of de novo enzymes in this way could be a promising strategy for creating tailored biocatalysts for many synthetically useful reactions. PMID- 27196437 TI - Stability and fluctuation of personality disorder features in daily life. AB - Very little is known about the daily stability and fluctuation of personality pathology. To address this gap in knowledge, we investigated the naturalistic manifestation of personality pathology over the course of 100 days. A group of individuals (N = 101) diagnosed with any personality disorder (PD) completed a daily diary study over 100 consecutive days (Mdn = 94 days, range = 33-101 days). Participants completed daily ratings of 30 manifestations of personality pathology. Patterns of stability and variability over the course of the study were then examined. Results indicated that individual PD manifestations and domains of PD manifestations were variable across days and differed widely in their frequency. Additionally, individual averages and level of variability in PD domains were highly stable across months, individual averages of PD domains were predicted by baseline dispositional ratings of PD traits with a high degree of specificity, and daily variability PD domains was associated with elevated levels of PD traits. This pattern of findings suggests that dynamic processes of symptom exacerbation and diminution that are stable in mean level and variability in expression over time characterizes personality pathology. Further, dispositional ratings are significant predictors of average daily expression of PD features. (PsycINFO Database Record PMID- 27196439 TI - Ultrasound for Distal Forearm Fracture: A Systematic Review and Diagnostic Meta Analysis. AB - STUDY OBJECTIVE: To determine the diagnostic accuracy of ultrasound for detecting distal forearm fractures. METHODS: A systematic review and diagnostic meta analysis was performed according to the PRISMA statement. We searched MEDLINE, Web of Science and the Cochrane Library from inception to September 2015. All prospective studies of the diagnostic accuracy of ultrasound versus radiography as the reference standard were included. We excluded studies with a retrospective design and those with evidence of verification bias. We assessed the methodological quality of the included studies with the QUADAS-2 tool. We performed a meta-analysis of studies evaluating ultrasound to calculate the pooled sensitivity and specificity with 95% confidence intervals (CI95%) using a bivariate model with random effects. Subgroup and sensitivity analysis were used to examine the effect of methodological differences and other study characteristics. RESULTS: Out of 867 publications we included 16 studies with 1,204 patients and 641 fractures. The pooled test characteristics for ultrasound were: sensitivity 97% (CI95% 93-99%), specificity 95% (CI95% 89-98%), positive likelihood ratio (LR) 20.0 (8.5-47.2) and negative LR 0.03 (0.01-0.08). The corresponding pooled diagnostic odds ratio (DOR) was 667 (142-3,133). Apparent differences were shown for method of viewing, with the 6-view method showing higher specificity, positive LR, and DOR, compared to the 4-view method. CONCLUSION: The present meta-analysis showed that ultrasound has a high accuracy for the diagnosis of distal forearm fractures in children when used by proper viewing method. Based on this, ultrasound should be considered a reliable alternative, which has the advantages of being radiation free. PMID- 27196440 TI - Common miR-590 Variant rs6971711 Present Only in African Americans Reduces miR 590 Biogenesis. AB - MicroRNAs (miRNAs) are recognized as important regulators of cardiac development, hypertrophy and fibrosis. Recent studies have demonstrated that genetic variations which cause alterations in miRNA:target interactions can lead to disease. We hypothesized that genetic variations in miRNAs that regulate cardiac hypertrophy/fibrosis might be involved in generation of the cardiac phenotype in patients diagnosed with hypertrophic cardiomyopathy (HCM). To investigate this question, we Sanger sequenced 18 miRNA genes previously implicated in myocyte hypertrophy/fibrosis and apoptosis, using genomic DNA isolated from the leukocytes of 199 HCM patients. We identified a single nucleotide polymorphism (rs6971711, C57T SNP) at the 17th position of mature miR-590-3p (= 57th position of pre-miR-590) that is common in individuals of African ancestry. SNP frequency was higher in African American HCM patients (n = 55) than ethnically-matched controls (n = 100), but the difference was not statistically significant (8.2% vs. 6.5%; p = 0.5). Using a cell culture system, we discovered that presence of this SNP resulted in markedly lower levels of mature miR-590-5p (39 +/- 16%, p<0.003) and miR-590-3p (20 +/- 2%, p<0.003), when compared with wild-type (WT) miR-590, without affecting levels of pri-miR-590 and pre-miR-590. Consistent with this finding, the SNP resulted in reduced target suppression when compared to WT miR-590 (71% suppression by WT vs 60% suppression by SNP, p<0.03). Since miR-590 can regulate TGF-beta, Activin A and Akt signaling, SNP-induced reduction in miR 590 biogenesis could influence cardiac phenotype by de-repression of these signaling pathways. Since the SNP is only present in African Americans, population studies in this patient population would be valuable to investigate effects of this SNP on myocyte function and cardiac physiology. PMID- 27196443 TI - CoYoT1 Clinic: Innovative Telemedicine Care Model for Young Adults with Type 1 Diabetes. AB - BACKGROUND: Young adults with type 1 diabetes (T1D) face many challenges in managing their diabetes, resulting in suboptimal glycemic control and often loss to follow-up. Comprehensive strategies are needed to engage this population in diabetes care and improve outcomes. This pilot study investigated the feasibility and acceptability of the Colorado Young Adults with Type 1 Diabetes (CoYoT1) Clinic-an innovative clinical care model for young adults with T1D, incorporating telemedicine and peer interactions. SUBJECTS AND METHODS: Forty-five patients with T1D, 18-25 years of age, participated in this study. Patients completed one routine, diabetes clinic appointment, using Health Insurance Portability and Accountability-approved, Web-based videoconferencing from a location of their choosing. The clinic visit consisted of an individual appointment with a diabetes provider and a group appointment with other young adults, facilitated by a certified diabetes educator. Patients completed a satisfaction survey and reported the time lost from school or work to complete the virtual appointment compared with time typically lost to complete a traditional, in-person, visit. RESULTS: Patients reported high levels of satisfaction with the virtual clinic and high levels of perceived support from the peer interaction. Additionally, patients reported saving over 6 h from their work or school day when completing their diabetes clinic visit virtually instead of in-person. CONCLUSIONS: In this cross-sectional pilot study, the CoYoT1 Clinic, incorporating Web-based videoconferencing and peer interactions, was feasible and acceptable for young adults with T1D. This model may potentially increase engagement with diabetes care in the young adult population. However, further research is needed to fully evaluate the intervention. PMID- 27196441 TI - A bout analysis reveals age-related methylmercury neurotoxicity and nimodipine neuroprotection. AB - Age-related deficits in motor and cognitive functioning may be driven by perturbations in calcium (Ca(2+)) homeostasis in nerve terminals, mechanisms that are also thought to mediate the neurotoxicity of methylmercury (MeHg). Calcium channel blockers (CCBs) protect against MeHg toxicity in adult mice, but little is known about their efficacy in other age groups. Two age groups of BALB/c mice were exposed to 0 or 1.2mg/kg/day MeHg and 0 or 20mg/kg/day of the CCB nimodipine for approximately 8.5 months. Adults began exposure on postnatal day (PND) 72 and the retired breeders on PND 296. High-rate operant behavior was maintained under a percentile schedule, which helped to decouple response rate from reinforcer rate. Responding was analyzed using a log-survivor bout analysis approach that partitioned behavior into high-rate bouts separated by pauses. MeHg-induced mortality did not depend on age but nimodipine neuroprotection was age-dependent, with poorer protection occurring in older mice. Within-bout response rate (a marker of sensorimotor function) was more sensitive to MeHg toxicity than bout initiation rate (a marker of motivation). Within-bout rate declined almost 2 months prior to overt signs of toxicity for the MeHg-only retired breeders but not adults, suggesting greater delay to toxicity in younger animals. Motor-based decrements also appeared in relatively healthy adult MeHg+NIM animals. Aging appeared to alter the processes underlying Ca(2+) homeostasis thereby diminishing protection by nimodipine, even in mice that have not reached senescence. The study of MeHg exposure presents an experimental model by which to study potential mechanisms of aging. PMID- 27196445 TI - gamma-Glutamyl Transferase Is an Independent Biomarker of Splanchnic Thrombosis in Patients With Myeloproliferative Neoplasm. AB - Myeloproliferative neoplasms (MPNs) are associated with an increased risk of thrombotic events and constitute the major risk factor of splanchnic venous thrombosis (SVT) in Western countries. Although timely anticoagulation resolves SVT, unrecognized SVT frequently leads to portal hypertension and, potentially, variceal bleeding, which may render anticoagulation difficult. Thus, early identification of SVT development is clinically relevant in MPN patients.In this retrospective analysis, we included 126 patients with MPN and/or SVT referred to our hospital between 2009 and 2014. A total of 86 patients diagnosed with MPN formed the first cohort (PV n = 18, ET n = 16, and MF n = 40), whereas 40 patients who had SVT without adjunct MPN formed a control cohort. Median follow up period was 960 days. Clinical and laboratory data were collected and analyzed for the identification of potential biomarkers applying descriptive statistics, nonparametric testing, Kaplan-Meier, and logistic regression analysis. The relevance of the identified biomarkers was evaluated in an independent 2nd cohort of 181 patients from the MPN registry of the Study Alliance of Leukemia (SAL MPN).Thirty-three MPN patients (38%) in the 1st cohort had SVT. Elevated levels of aspartate aminotransferase, alanine aminotransferase, serum bilirubin, or gamma-GT were significantly correlated to the presence of SVT. In multivariate testing, CRP and aspartate aminotransferase were predictors for survival and gamma-GT remained the only significant variable associated with SVT in MPN patients (P < 0.05). These findings were confirmed in the 2nd cohort comprising 42% of patients with MPN suffering from SVT.Elevated gamma-GT levels indicate SVT in MPN patients, whereas CRP levels are independent predictors of patient survival. PMID- 27196444 TI - Karyomegalic Interstitial Nephritis: A Case Report and Review of the Literature. AB - Karyomegalic interstitial nephritis is a rare cause of hereditary chronic interstitial nephritis, described for the first time over 40 years ago.A 36-year old woman, of Turkish origin, presented with chronic kidney disease and high blood pressure. She had a history of recurrent upper respiratory tract infections but no familial history of nephropathy. Physical examination was unremarkable. Laboratory tests showed serum creatinine at 2.3 mg/dL with an estimated glomerular filtration rate of 26 mL/min/1.73m, and gamma-glutamyl transpeptidase and alkaline phosphatase at 3 and 1.5 times the upper normal limit. Urinalysis showed 0.8 g/day of nonselective proteinuria, microscopic hematuria, and aseptic leukocyturia. Immunological tests and tests for human immunodeficiency and hepatitis B and C viruses were negative. Complement level and serum proteins electrophoresis were normal. Analysis of the renal biopsy showed severe interstitial fibrosis and tubular atrophy. Numerous tubular cells had nuclear enlargement with irregular outlines, hyperchromatic aspect, and prominent nucleoli. These findings were highly suggestive of karyomegalic interstitial nephritis, which was further confirmed by exome sequencing of FAN1 gene showing an identified homozygous frameshift mutation due to a one-base-pair deletion in exon 12 (c.2616delA).The present case illustrates a rare but severe cause of hereditary interstitial nephritis, sometimes accompanied by subtle extrarenal manifestations. Identification of mutations in FAN1 gene underscores recent insights linking inadequate DNA repair and susceptibility to chronic kidney disease. PMID- 27196447 TI - Comparisons of Different Screening Tools for Identifying Fracture/Osteoporosis Risk Among Community-Dwelling Older People. AB - A prospective study was conducted to compare criterion, predictive, and construct validities of 9 fracture/osteoporosis assessment tools, including calcaneal quantitative ultrasonography (QUS), Age Bulk One or Never Estrogens (ABONE), body weight criterion (BWC), Fracture Risk Assessment Tool (FRAX), Garvan fracture risk calculator (GARVAN), Osteoporosis Risk Assessment Instrument (ORAI), Osteoporosis Index of Risk (OSIRIS), Osteoporosis Self-Assessment Tool for Asians (OSTA), and Simple Calculated Osteoporosis Risk Estimation (SCORE), among older men and women in Taiwan.Using the femoral neck dual-energy x-ray absorptiometry (DXA) T-score as an external criterion, the sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios, and the area under the receiver operating characteristic curve (AUC) for each tool were calculated. The ability of these tools to predict injurious falls was examined. A principal component analysis was applied to understand whether these tools were measuring the same underlying construct.The FRAX, BWC, ORAI, OSIRIS, OSTA, and SCORE had AUCs of >=0.8 in men, while the GARVAN, OSIRIS, OSTA, and SCORE had AUCs of >=0.8 in women. The sensitivity, negative predictive value, and likelihood ratio of the ABONE, BWC, ORAI, OSIRIS, OSTA, and SCORE tools in both men and women were 100%, >=90%, and 0.0, respectively; the specificity and positive predictive value and likelihood ratio were far from satisfactory. The GARVAN displayed the best predictive ability of a fall in both men (AUCs, 0.653 0.686) and women (AUCs, 0.560-0.567), despite being smaller in women. The 9 screening tools and 2 central DXA measurements assessed 5 different factors, while the ABONE, BWC, ORAI, OSIRIS, OSTA, and SCORE measured the same one.Simple self-assessment tools can serve as initial screening instruments to rule out persons who have osteoporosis; however, these tools may measure a different construct other than fracture/osteoporosis risk. PMID- 27196446 TI - An Observational Study on Aberrant Methylation of Runx3 With the Prognosis in Chronic Atrophic Gastritis Patients. AB - The aim of this study is to discuss whether the methylation levels of Runx3 could be used as the early biomarker for predicting the prognosis in chronic atrophic gastritis (CAG) patients. A total of 200 subjects including 60 controls without CAG (Group 1), 70 patients with mild CAG (Group 2), and 70 patients with moderate and severe CAG (Group 3) were recruited for this cross-sectional investigation in the Department of Gastroenterology in Daqing Oilfield General Hospital from July 2013 to May 2014. The MlALDI-TOF-MS was used to measure the methylation levels of Runx3 in all of the subjects. Real-time quantitative reverse transcription polymerase chain reaction and western blotting were chosen to determine the expression levels of Runx3. The correlations between methylation levels of Runx3 among these CAG patients and their prognosis were shown by logistic regression models. The results demonstrated that the methylation levels of CpG13, CpG14, and CpG15 in Runx3 were higher in Group 3 than those in Groups 1 and 2 (P <0.05), whereas the mRNA and protein expression levels of Runx3 were lower in Group 3 than those in Groups 1 and 2 (P <0.05). There were significantly negative correlations between the methylation levels of Runx3 with its expression and the healing prognosis of CAG patients. In brief, this study proved that the hypermethylation modifications of CpG13, CpG14, and CpG15 in the promoter region of Runx3 could result in the down regulation of Runx3 expression to affect the prognosis of CAG. So the methylation levels of these CpG sites in Runx3 in the peripheral blood can be used as the biomarker for predicting the healing prognosis of CAG patients. PMID- 27196448 TI - Clinical Outcomes for Systemic Corticosteroids Versus Vincristine in Treating Kaposiform Hemangioendothelioma and Tufted Angioma. AB - A meta-analysis was performed to evaluate the efficacy and safety of systemic corticosteroids versus those of vincristine in the treatment of kaposiform hemangioendothelioma (KHE) and tufted angioma (TA).A literature search of PubMed, Embase, and Web of Science was performed for clinical studies on systemic corticosteroid versus vincristine therapies in treating KHE/TA. Pooled relative risks (RRs) and response rate with 95% confidence intervals (CIs) were used to measure outcomes. Heterogeneity, subgroup analysis, sensitivity analysis, and publication bias analysis were performed for result evaluation.Thirteen studies, comprising 344 participants, were used in the analysis. Vincristine therapy was found to be relatively more effective than systemic corticosteroids (RRs = 0.45, 95%CI: 0.35-0.58). The result of pooled adverse reactions response rate for systemic corticosteroids was 0.31 (95%CI, 0.18-0.43), significantly higher than that for vincristine, which was 0.12 (95%CI, 0.06-0.19). In subgroup analyses, factors including mean age and race of patients, and period of follow-up were examined as possible sources of heterogeneity.This is the first meta-analysis estimating the clinical outcomes of systemic corticosteroids in comparison with those of vincristine in the treatment of KHE/TA. The results showed that vincristine was considerably more effective with lower complication rates than systemic corticosteroids; thus, vincristine could be suggested as the first-line therapy for KHE/TA. PMID- 27196449 TI - Transient Elastography is Superior to FIB-4 in Assessing the Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B. AB - Liver stiffness (LS), assessed using transient elastography (TE), and (FIB-4) can both estimate the risk of developing hepatocellular carcinoma (HCC). We compared prognostic performances of LS and FIB-4 to predict HCC development in patients with chronic hepatitis B (CHB).Data from 1308 patients with CHB, who underwent TE, were retrospectively analyzed. FIB-4 was calculated for all patients. The cumulative rate of HCC development was assessed using Kaplan-Meier curves. The predictive performances of LS and FIB-4 were evaluated using time-dependent receiver-operating characteristic (ROC) curves.The mean age (883 men) was 50 years. During follow-up (median 6.1 years), 119 patients developed HCC. The areas under the ROC curves (AUROCs) predicting HCC risk at 3, 5, and 7 years were consistently greater for LS than for FIB-4 (0.791-0.807 vs 0.691-0.725; all P < 0.05). Similarly, when the respective AUROCs for LS and FIB-4 at every time point during the 7-year follow-up were plotted, LS also showed consistently better performance than FIB-4 after 1 year of enrollment. The combined use of LS and FIB 4 significantly enhanced the prognostic performance compared with the use of FIB 4 alone (P < 0.05), but the performance of the combined scores was statistically similar to that of LS alone (P > 0.05).LS showed significantly better performance than FIB-4 in assessing the risk of HCC development, and the combined use of LS and FIB-4 did not provide additional benefit compared with the use of LS alone. Hence, LS assessed using TE might be helpful for optimizing HCC surveillance strategies. PMID- 27196450 TI - Increased Risk of Acute Coronary Syndrome in Patients With Chronic Pancreatitis: A Nationwide Cohort Analysis. AB - Chronic inflammation may promote development of coronary heart disease. Studies on the relationship between chronic pancreatitis (CP) and cardiovascular diseases are scant.We conducted a nationwide retrospective cohort study to determine the risk of acute coronary syndrome (ACS) in patients with CP.We randomly selected a comparison cohort of individuals without CP from the Taiwan National Health Insurance Research Database (N = 23.74 million) and frequency-matched them with patients with CP from 2000 to 2010 in a 1:4 ratio according to age, sex, and index year. The follow-up period lasted from the index date of the new CP diagnosis to the date of ACS diagnosis, censoring, or the end of 2011. We analyzed the risk of ACS by using Cox proportional-hazard models.In total, 17,405 patients with CP and 69,620 individuals without CP were followed for 84,430 and 417,426 person-years. Most patients with CP were men, and the mean age of the patients was 48.3 +/- 15.0 years. The overall ACS incidence was 2.15-fold higher in the CP cohort than in the non-CP cohort (4.89 vs 2.28 per 10,000 person-years) with an adjusted hazard ratio (aHR) of 1.40 (95% confidence interval [CI] 1.20 1.64). Compared with individuals without CP, patients with CP aged <=39 years exhibited the highest risk of ACS (aHR 2.14, 95% CI 1.13-4.02), followed by those aged 40 to 54 years (aHR 1.66, 95% CI 1.23-2.24) and those aged 55 to 69 years (aHR 1.53, 95% CI 1.15-2.03).CP may become an independent risk factor for ACS. PMID- 27196451 TI - Primary Thyroid Extranasal NK/T-Cell Lymphoma Associated With Good Outcome: A Case Report and Literature Review: A Care-Compliant Article. AB - Most thyroid lymphomas are B-lineage, and T-cell lymphomas are rare. None of primary thyroid extranasal NK/T-cell lymphoma (NKTCL) has been reported in the literature. Here, we report a case of extranasal NKTCL exclusively arising in the thyroid in an 18-year-old Chinese.The patient presented with rapid anterior swelling at the neck and aggravated dyspnea for 2 months. Neck computer tomography scan revealed diffuse thyroid enlargement in the left lobe compressing the trachea. The thyroid function test was indicative of hypothyroidism. Gastroscopy demonstrated chronic nonspecific gastritis. Subtotal thyroidectomy was performed. Histological examination showed a diffuse infiltration of neoplastic lymphoid cells with an angiodestructive behavior. Immunophenotype is positive for CD2, CD56, CD43, and TIA-1, and typically negative for surface CD3. Epstein-Barr virus-encoded small RNAs were detected in tumor cells. A diagnose of primary thyroid extranasal NKTCL-N lymphoma was confirmed by the findings.The patient was treated with CHOP-L combination chemotherapy followed by local radiotherapy, and tolerated the modality well. The patient has been in remission for 28 months so far.To our knowledge, this is the first case report of primary extranasal NKTCL exclusively arising in the thyroid. The case has a relatively good treatment outcome with timely diagnosis and multimodality approach. PMID- 27196452 TI - Steroid Injection Versus Physiotherapy for Patients With Adhesive Capsulitis of the Shoulder: A PRIMSA Systematic Review and Meta-Analysis of Randomized Controlled Trials. AB - To compare the effect of steroid injection and physiotherapy for patients with adhesive capsulitis of the shoulder (ACS).An electronic search was performed on Pubmed, Embase, and Cochrane library, and reference lists were also reviewed for randomized controlled trials (RCTs) comparing steroid injection and physiotherapy for patients with ACS. The quality of included studies were assessed using PEDro scale. Standardized mean differences (SMDs) and 95% confidence interval (CI) were used for comparisons. The primary outcome was functional improvement.Nine RCTs including 453 patients were identified. From 6-7 weeks to 24-26 weeks postintervention, no superiority was noted in favor of either steroid injection or physiotherapy for functional improvement (SMD 0.28; 95% CI -0.01-0.58; P = 0.06) or pain relief (SMD -0.10; 95% CI -0.70-0.50; P = 0.75). Steroid injection provided more improvement in passive external rotation at 24 to 26 weeks (3 studies, SMD 0.42; 95% CI 0.11-0.72; P = 0.007) but not at 6 to 7 weeks (4 studies, SMD 0.63; 95% CI 0.36-0.89; P = 0.32) or 12 to 16 weeks (3 studies, SMD 0.07; 95% CI -0.79-0.65; P = 0.85). Steroid injection was as safe as physiotherapy for patients with ACS (risk ratio 0.94; 95% CI 0.67-1.31).Both steroid injection and physiotherapy are equally effective for patients with ACS. One steroid injection might be the 1st choice for ACS. Results should be interpreted with caution due to the heterogeneity among the studies. PMID- 27196453 TI - Prevalence and Consequences of the Proximal Junctional Kyphosis After Spinal Deformity Surgery: A Meta-Analysis. AB - The aim of this study was to estimate the prevalence and patient outcomes of proximal junctional kyphosis (PJK) in pediatric patients and adolescents who received surgical interventions for the treatment of a spinal deformity.Literature was searched in electronic databases, and studies were selected by following precised eligibility criteria. Percent prevalence values of the PJK in individual studies were pooled to achieve a weighted effect size under the random effects model. Subgroup and meta-regression analyses were performed to appraise the factors affecting PJK prevalence.Twenty-six studies (2024 patients) were included in this meta-analysis. Average age of the patients was 13.8 +/- 2.75 years of which 32 +/- 20 % were males. Average follow-up was 51.6 +/- 38.8 (range 17 +/- 13 to 218 +/- 60) months. Overall, the percent prevalence of PJK (95% confidence interval) was 11.02 (10.5, 11.5) %; P < 0.00001 which was inversely associated with age (meta-regression coefficient: -1.607 [-2.86, 0.36]; 0.014). Revision surgery rate in the patients with PJK was 10%. The prevalence of PJK was positively associated with the proximal junctional angle at last follow-up (coefficient: 2.248; P = 0.012) and the change in the proximal junctional angle from surgery to last follow-up (coefficient: 2.139; P = 0.014) but not with preoperative proximal junctional angle.The prevalence of PJK in the children and adolescent patients is 11%. About 10% of those affected require revision surgery. PMID- 27196454 TI - Cost-Effectiveness of Bariatric Surgery for Type 2 Diabetes Mellitus: A Randomized Controlled Trial in China. AB - To compare the remission of type 2 diabetes mellitus (T2DM) through treatment with laparoscopic sleeve gastrectomy (LSG) or laparoscopic Roux-en-Y gastric bypass (LRYGB), and to analyze the cost-effectiveness of medical treatment, LSG, and LRYGB in T2DM patients (BMI >= 28).A 2-group randomized controlled trial was conducted at Diabetes Surgery Centre, Beijing Shijitan Hospital in Beijing, China. Subjects were 80 patients ages 16 to 65 years with a body mass index of 28 kg/m or more and duration of T2DM no more than 15 years. Subjects were randomly assigned (1:1) to undergo either LSG (n = 40) or LRYGB (n = 40) between February 3, 2011 and October 31, 2013. Of those patients, 72 (90%) were available at follow-up at 2 years. These patients included 34 (85%) who underwent LSG and 38 (95%) who underwent LRYGB. This study presents the follow-up data at 2 years, which compared LSG and LRYGB in T2DM patients. Partial remission and complete remission were determined, and weight loss, BMI, changes in abdominal circumference, cholesterol, and triglycerides were measured. The cost effectiveness of each type of bariatric surgery was analyzed with a Markov simulation model that yielded quality-adjusted life-years (QALYs) and costs.From our analysis results, LSG and LRYGB are both have taken a great effect on the reduction of fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), and bodyweight in patients with T2DM. The cost-effectiveness ratios of medical treatment, LSG, and LRYGB respectively are 1589.02, 1028.97, and 1197.44 dollars per QALY.Our analysis indicates that LSG appear to provide a cost-effective method of T2DM treatment for the patients. PMID- 27196455 TI - Predictive Factors of Biliary Tract Cancer in Anomalous Union of the Pancreaticobiliary Duct. AB - The assessment of malignancies associated with anomalous union of the pancreaticobiliary duct (AUPBD) is essential for the design of appropriate treatment strategies. The aim of the present study is to measure the incidence of AUPBD-related pancreaticobiliary malignancy and to identify predictive factors. This retrospective cohort study included cases of 229 patients with AUPBD between January 1999 and December 2013. The impact of bile duct dilatation on the incidence of AUPBD-related pancreaticobiliary disease was measured, and predictive factors were evaluated.Among 229 patients with AUPBD, 152 had common bile duct dilatation (>=10 mm) (dilated group) and 77 did not (<10 mm) (nondilated group). Intrahepatic cholangiocarcinoma occurred more frequently in the nondilated group than in the dilated group (3.9% vs 0%; P < 0.05). By contrast, no significant difference in the incidence of extrahepatic cholangiocarcinoma was observed between the 2 groups (1.3% vs 3.9%; P = 0.271). By univariate analysis, age, type of AUPBD, and the level of pancreatic enzymes refluxed in the bile duct were associated with occurrence of biliary tract cancers. In multivariate analysis, age >=45 years (odds ratio [OR] 1.042, 95% confidence interval [CI] 1.011-1.073, P < 0.05), P-C type (OR 3.327, 95% CI 1.031 10.740, P < 0.05), and a high level of biliary lipase (OR 4.132, 95% CI 1.420 12.021, P < 0.05) showed a significant association with AUPBD-related biliary tract cancer.Intrahepatic cholangiocarcinoma may occur more frequently in AUPBD patients without bile duct dilatation. Age >=45 years, P-C type, and biliary lipase level >=45,000 IU/L are significantly associated with AUPBD-related biliary tract cancer. PMID- 27196456 TI - Using Flat-Panel Perfusion Imaging to Measure Cerebral Hemodynamics: A Pilot Feasibility Study in Patients With Carotid Stenosis. AB - Flat-detector CT perfusion (FD-CTP) imaging has demonstrated efficacy in qualitatively accessing the penumbra in acute stroke equivalent to that of magnetic resonance perfusion (MRP). The aim of our study was to evaluate the feasibility of quantifying oligemia in the brain in patients with carotid stenosis.Ten patients with unilateral carotid stenosis of >70% were included. All MRPs and FD-CTPs were performed before stenting. Region-of-interests (ROIs) including middle cerebral artery territory at basal ganglia level on both stenotic and contralateral sides were used for quantitative analysis. Relative time to peak (rTTP) was defined as TTP of the stenotic side divided by TTP of the contralateral side, and so as relative cerebral blood volume (rCBV), relative mean transit time (rMTT), and relative cerebral blood flow (rCBF). Absolute and relative TTP, CBV, MTT, CBF between two modalities were compared.For absolute quantitative analysis, the correlation of TTP was highest (r = 0.56), followed by CBV (r = 0.47), MTT (r = 0.47), and CBF (r = 0.43); for relative quantitative analysis, rCBF was the highest (r = 0.79), followed by rTTP (r = 0.75) and rCBV (r = 0.50).We confirmed that relative quantitative assessment of FD-CTP is feasible in chronic ischemic disease. Absolute quantitative measurements between MRP and FD-CTP only expressed moderate correlations. Optimization of acquisitions and algorithms is warranted to achieve better quantification. PMID- 27196457 TI - Acrodermatitis Enteropathica: A Case Report. AB - Acrodermatitis enteropathica is a rare genetic autosomal recessive disorder, characterized by periorificial dermatitis, alopecia, and diarrhea. It is caused by mutations in the gene that encodes a membrane protein that binds zinc. We report a 14-month-old boy, admitted for erythematous, scaly and pustular lesions, initially located in the inguinal and perianal regions and on thighs, and very few erythematous lesions on the face. Due to the numerous bacterial skin superinfections with Staphylococcus aureus, including abscesses that required surgical incision, the clinical picture was modified, leading to a delayed establishment of the diagnosis. Later, the symptoms became suggestive for this disease, the diagnostic having been confirmed by low plasma zinc values. Under zinc therapy, skin lesions improved significantly in a few days, with favorable outcome. Two months later, the skin lesions almost disappeared.Abscesses due to bacterial skin superinfections may lead to initially misdiagnosed acrodermatitis enteropathica. PMID- 27196458 TI - Medication Adherence and Blood Pressure Control Among Hypertensive Patients With Coexisting Long-Term Conditions in Primary Care Settings: A Cross-Sectional Analysis. AB - Hypertension is a typical example of long-term disease posing formidable challenges to health care. One goal of antihypertensive therapy is to achieve optimal blood pressure (BP) control and reduce co-occurring chronic conditions (multimorbidity). This study aimed to assess the influence of multimorbidity on medication adherence, and to explore the association between poor BP control and multimorbidity, with implications for hypertension management.A cross-sectional design with multistage sampling was adopted to recruit Chinese hypertensive patients attending general out-patient clinics from 3 geographic regions in Hong Kong. A modified systemic sampling methodology with 1 patient as a sampling unit was used to recruit consecutive samples in each general out-patient clinic. Data were collected by face-to-face interviews using a standardized protocol. Poor BP control was defined as having systolic BP/diastolic BP >=130/80 mm Hg for those with diabetes or chronic kidney disease; and >=140/90 mm Hg for others. Medication adherence was assessed by a validated Chinese version of the Morisky Medication Adherence Scale. A simple unweighted enumeration was adopted to measure the combinations of coexisting long-term conditions. Binary logistic regression analysis was conducted with medication adherence and multimorbidity as outcome variables, respectively, after controlling for effects of patient-level covariates.The prevalence of multimorbidity was 47.4% (95% confidence interval [CI] 45.4%-49.4%) among a total of 2445 hypertensive patients. The proportion of subjects having 0, 1, and >=2 additional long-term conditions was 52.6%, 29.1%, and 18.3%, respectively. The overall rate of poor adherence to medication was 46.6%, whereas the rate of suboptimal BP control was 48.7%. Albeit the influence of multimorbidity on medication adherence was not found to be statistically significant, patients with poorly controlled BP were more likely to have multimorbidity (adjusted odds ratio 2.07, 95% CI 1.70-2.53, P < 0.001). Diabetes was the most prevalent concomitant long-term condition among hypertensive patients with poor BP control (38.6%, 95% CI 35.8-41.4 vs 19.7%, 95% CI 17.5-21.9 for patients with good BP control, P < 0.001).Multimorbidity was common among hypertensive patients, and was associated with poor BP control. Subjects with coexisting diabetes, heart disease, or chronic kidney disorder should receive more clinical attention to achieve better clinical outcomes. PMID- 27196459 TI - Association Between Psoriasis and Subclinical Atherosclerosis: A Meta-Analysis. AB - The association between psoriasis and carotid intima-media thickness (CIMT) or impaired flow-mediated dilation (FMD) remains controversial. We aimed to evaluate the extent of subclinical atherosclerosis as measured by CIMT and FMD in patients with psoriasis by conducting a meta-analysis.A systematic literature search was performed using PubMed, Embase, Cochrane databases, China National Knowledge Infrastructure, and VIP databases up to February 2015. Observational studies investigating CIMT or FMD in patients with psoriasis and controls were eligible. Psoriatic patients and controls were at least age- and sex-matched. Random effects analysis was used to estimate the weighted mean difference (WMD) and 95% confidence interval (CI) between psoriatic patients and controls.A total of 20 studies were identified and analyzed. Meta-analysis showed that psoriatic patients had a significantly thicker CIMT (WMD 0.11 mm; 95% CI 0.08-0.15) and lower FMD (WMD -2.79%; -4.14% to -1.43%) than those in controls. Subgroup analysis indicated that psoriatic arthritis appeared to have less impaired FMD (WMD -2.45%) and thinner CIMT (WMD 0.10 mm). Psoriatic patients with mean age >45 years had much thicker CIMT (WMD 0.13 mm). The impaired FMD (WMD -3.99%) seemed more pronounced in psoriatic patients with mean age <45 years.This meta-analysis suggests that patients with psoriasis are associated with excessive risk of subclinical atherosclerosis. Screening and monitoring CIMT and brachial artery FMD may be recommended to identify a subgroup of psoriatic patients at higher risk for cardiovascular events. PMID- 27196460 TI - Efficacy and Safety of Celecoxib Therapy in Osteoarthritis: A Meta-Analysis of Randomized Controlled Trials. AB - Osteoarthritis (OA) is the most common form of arthritis in older individuals and is among the most prevalent and disabling chronic conditions worldwide.We conducted a meta-analysis to determine the efficacy and safety of celecoxib, a cyclooxygenase-2 (COX-2) inhibitor in the treatment of osteoarthritis. Studies were pooled, and mean difference (MD), relative risk (RR), and its corresponding 95% confidence interval (CI) were calculated. Fifteen relevant articles were included for this meta-analysis study.We observed that osteoarthritis total score (MD = -4.41, 95% CI -7.27 to -1.55), pain subscale score (MD = -0.86, 95% CI 1.10 to -0.62), and function subscale score (MD = -2.90, 95% CI -5.12 to -0.67) in OA patients treatment with celecoxib was significantly improved than that with placebo. There was no significant difference in the incidence of adverse events (AEs), SAEs, and discontinuations due to AEs; however, the incidence of gastrointestinal AEs in OA patients treatment with celecoxib is significantly higher than that with placebo. For AE, the incidence of abdominal pain in OA patients with celecoxib was significantly higher than that with placebo (RR = 2.24, 95% CI: 1.40-3.58; P = 0.839, I = 0%). There was no significant difference in diarrhea, dyspepsia, headache, and nausea.This meta-analysis indicated that celecoxib treatment (200 mg orally once daily) led to significant improvement in the pain and function of osteoarthritis. However, compared with placebo control, celecoxib resulted in greater gastrointestinal AEs, especially abdominal pain after approximately 10 to 13 weeks of treatment. The current study, therefore, provides valuable information to help physicians make treatment decisions for their patients with OA. PMID- 27196461 TI - The Use of Apatinib in Treating Nonsmall-Cell Lung Cancer: Case Report and Review of Literature. AB - Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, which has been proved to be effective and safe in treating heavily pretreated patients with gastric cancer.The aim of the study was to explore the use of apatinib in treatment of nonsmall cell lung cancer and its side effects.We report 2 patients presented with advanced nonsmall-cell lung cancer, who received apatinib after failure in the first- or third-line chemotherapy. They are treated with apatinib in daily dose of 850 mg, 28 days per cycle.Favorable oncologic outcomes were achieved in the 2 cases after the treatment of apatinib. Patient I's progression-free-survival has increased to 4.6 months after palliative therapy of apatinib, whereas Patient II nearly 6 months. The common side effects of apatinib were hypertension and hand-foot syndrome; however, the toxicity of apatinib was controllable and tolerable.Apatinib may be an option for advanced nonsmall cell lung cancer after failure of chemotherapy or other targeted therapy. But that still warrants further investigation in the prospective study. PMID- 27196463 TI - Imaging Findings of Cerebral Amyloid Angiopathy, Abeta-Related Angiitis (ABRA), and Cerebral Amyloid Angiopathy-Related Inflammation: A Single-Institution 25 Year Experience. AB - Vascular inflammation is present in a subset of patients with cerebral amyloid angiopathy (CAA) and has a major influence in determining the disease manifestations. Radiological characterization of this subset is particularly important to achieve early recognition and treatment. We conducted this study to investigate the role of imaging in differentiating CAA with and without inflammation. We reviewed neuroimaging findings for 54 patients seen at Mayo Clinic over 25 years with pathological evidence of CAA and with available neuroimaging at the time of diagnosis. Clinical data were also recorded. Patients were grouped into CAA alone (no vascular inflammation), Abeta-related angiitis or ABRA (angiodestructive inflammation), and CAA-related inflammation or CAA-RI (perivascular inflammation). Imaging findings at presentation were compared among patient subgroups. Radiological features supporting a diagnosis of ABRA or CAA-RI were identified. Radiologic findings at diagnosis were available in 27 patients with CAA without inflammation, 22 with ABRA, and 5 with CAA-RI. On MRI, leptomeningeal disease alone or with infiltrative white matter was significantly more frequent at presentation in patients with ABRA or CAA-RI compared with those with CAA (29.6% vs. 3.7%, P = 0.02; and 40.7% vs. 3.7%, P = 0.002, respectively), whereas lobar hemorrhage was more frequent in patients with CAA (62.3% vs. 7.4%, P = 0.0001). Overall, leptomeningeal involvement at presentation was present in 70.4% of patients with ABRA or CAA-RI and in only 7.4% of patients with CAA (P = 0.0001). The sensitivity and specificity of leptomeningeal enhancement to identify patients with ABRA or CAA-RI were 70.4% and 92.6%, respectively, whereas the positive likelihood ratio (LR) was 9.5. The sensitivity and specificity of intracerebral hemorrhage to identify patients with CAA were 62.9% and 92.6%, respectively, whereas the positive LR was 8.5. Microbleeds were found in 70.4% of patients with inflammatory CAA at presentation. In conclusion, leptomeningeal enhancement and lobar hemorrhage at presentation may enable differentiation between CAA with and without inflammation. The identification at initial MRI of diffuse cortical-subcortical microbleeds in elderly patients presenting with infiltrative white matter process or prominent leptomeningeal enhancement is highly suggestive of vascular inflammatory CAA. PMID- 27196462 TI - Familial Clustering of Gastric Cancer: A Retrospective Study Based on the Number of First-Degree Relatives. AB - This comprehensive cross-sectional study aimed to identify factors contributing to familial aggregation of gastric cancer (GC). A total of 1058 GC patients and 1268 controls were analyzed separately according to the presence or absence of a first-degree relative of GC (GC-relative). Logistic regression analysis adjusted for age, gender, residence during childhood, smoking, alcohol intake, monthly income, spicy food ingestion, Helicobacter pylori status and host cytokine polymorphisms was performed. Cytotoxin-associated gene A (cagA) positivity was a distinctive risk factor for GC in the family history (FH)-positive group (odds ratio [OR], 2.39; 95% confidence interval [CI], 1.42-4.00), while current/ex smoker, moderate to strong spicy food ingestion, and non-B blood types were more closely associated with GC in the FH-negative group. Among the FH-positive group, alcohol consumption showed a synergistic carcinogenic effect in the at least 2 GC relatives group compared to the 1 GC-relative group (1.71 vs. 9.58, P for interaction = 0.026), and this was dose-dependent. In the subjects with >=2 GC relatives, TGFB1-509T/T was a risk factor for GC (OR 23.74; 95% CI 1.37-410.91), as were rural residency in childhood, alcohol consumption, spicy food ingestion, and cagA positivity. These results suggest that subjects with FH may be a heterogeneous group in terms of gastric cancer susceptibility. Especially, subjects with >=2 GC-relatives should undergo risk stratification including TGFB1 509T/T and alcohol consumption. PMID- 27196464 TI - Sonolysis in Prevention of Brain Infarction During Cardiac Surgery (SONORESCUE): Randomized, Controlled Trial. AB - Here, we examined whether intraoperative sonolysis can alter the risk of new ischemic lesions in the insonated brain artery territory during coronary artery bypass grafting (CABG) or valve surgery.Silent brain ischemic lesions could be detected in as many as two-thirds of patients after CABG or valve surgery.Patients indicated for CABG or valve surgery were allocated randomly to sonolysis (60 patients, 37 males; mean age, 65.3 years) of the right middle cerebral artery (MCA) during cardiac surgery and control group (60 patients, 37 males; mean age, 65.3 years). Neurologic examination, cognitive function tests, and brain magnetic resonance imaging (MRI) were conducted before intervention as well as 24 to 72 hours and 30 days after surgery.New ischemic lesions on control diffusion-weighted MRI in the insonated MCA territory >=0.5 mL were significantly less frequent in the sonolysis group than in the control group (13.3% vs 26.7%, P = 0.109). The sonolysis group exhibited significantly reduced median volume of new brain ischemic lesions (P = 0.026). Stenosis of the internal carotid artery >=50% and smoking were independent predictors of new brain ischemic lesions >=0.5 mL (odds ratio = 5.685 [1.272-25.409], P = 0.023 and 4.698 [1.092-20.208], P = 0.038, respectively). Stroke or transient ischemic attack occurred only in 2 control patients (P = 0.496). No significant differences were found in scores for postintervention cognitive tests (P > 0.05).This study provides class-II evidence that sonolysis during CABG or valve surgery reduces the risk of larger, new ischemic lesions in the brain.www.clinicaltrials.gov (NCT01591018). PMID- 27196465 TI - Variation of DNA Fragmentation Levels During Density Gradient Sperm Selection for Assisted Reproduction Techniques: A Possible New Male Predictive Parameter of Pregnancy? AB - Predicting the outcome of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) is one main goal of the present research on assisted reproduction. To understand whether density gradient centrifugation (DGC), used to select sperm, can affect sperm DNA integrity and impact pregnancy rate (PR), we prospectively evaluated sperm DNA fragmentation (sDF) by TUNEL/PI, before and after DGC. sDF was studied in a cohort of 90 infertile couples the same day of IVF/ICSI treatment. After DGC, sDF increased in 41 samples (Group A, median sDF value: 29.25% [interquartile range, IQR: 16.01-41.63] in pre- and 60.40% [IQR: 32.92-93.53] in post-DGC) and decreased in 49 (Group B, median sDF value: 18.84% [IQR: 13.70-35.47] in pre- and 8.98% [IQR: 6.24-15.58] in post-DGC). PR was 17.1% and 34.4% in Group A and B, respectively (odds ratio [OR]: 2.58, 95% confidence interval [CI]: 0.95-7.04, P = 0.056). After adjustment for female factor, female and male age and female BMI, the estimated OR increased to 3.12 (95% CI: 1.05 9.27, P = 0.041). According to the subgroup analysis for presence/absence of female factor, heterogeneity in the association between the Group A and B and PR emerged (OR: 4.22, 95% CI: 1.16-15.30 and OR: 1.53, 95% CI: 0.23-10.40, respectively, for couples without, n = 59, and with, n = 31, female factor).This study provides the first evidence that the DGC procedure produces an increase in sDF in about half of the subjects undergoing IVF/ICSI, who then show a much lower probability of pregnancy, raising concerns about the safety of this selection procedure. Evaluation of sDF before and after DGC configures as a possible new prognostic parameter of pregnancy outcome in IVF/ICSI. Alternative sperm selection strategies are recommended for those subjects who undergo the damage after DGC. PMID- 27196466 TI - Profile of the Older Population Living in Miami-Dade County, Florida: An Observational Study. AB - Florida has the greatest proportion (19%) of older population (65 years or older) in the United States. The age distribution of its residents, in conjunction with a major shift in the leading cause of death within all age groups from acute illnesses to chronic disease, creates unprecedented health care challenges for the state. The objective of this study is to profile the older population living in Miami-Dade County (MDC) using 3 population-based, household-based surveys conducted over the past 5 years.This study examined cross-sectional data (demographics, health outcomes, risk factors, health assess, and utilization) collected from probability-sampled, household-based surveys conducted in 3 areas of MDC: north Miami-Dade, Little Haiti, and South Miami. The questionnaire was administered face-to-face by trained interviewers in English, Spanish, French, or Creole. Analyses were restricted to households containing at least 1 member aged 65 years or older (n = 935). One consenting adult answered the questionnaire on behalf of household members.The mean age of the respondent (60% females) was 60 years. Overall, respondents were predominantly African-Americans, Hispanics, and blacks of Haitian origin. One-third of all households fell below the US poverty thresholds. One-quarter of all households had at least 1 member who was uninsured within the year before the survey. Twenty percent of households had at least 1 member with an acute myocardial infarction or stroke during the year before the survey. Bone density tests and blood stool tests were strikingly underutilized. The health outcomes most prevalent within household members were cardiovascular diseases followed by cancer, anxiety/depression, obesity, asthma, and bone fractures. Twenty percent of households reported having at least 1 current smoker. Overall, emergency rooms were the most commonly used places of care after doctor's offices.Findings of 3 household-based surveys show a predominantly elderly, female, uninsured, and poor minority populations living in MDC, FL. The reported use of preventive services was constrained, and emergency room use was often reported as a main resource for health care. Cardiovascular disease, cancer, bone fractures, and related risk factors were the most prevalent health outcomes. PMID- 27196467 TI - Quality Reporting of Multivariable Regression Models in Observational Studies: Review of a Representative Sample of Articles Published in Biomedical Journals. AB - Controlling for confounders is a crucial step in analytical observational studies, and multivariable models are widely used as statistical adjustment techniques. However, the validation of the assumptions of the multivariable regression models (MRMs) should be made clear in scientific reporting. The objective of this study is to review the quality of statistical reporting of the most commonly used MRMs (logistic, linear, and Cox regression) that were applied in analytical observational studies published between 2003 and 2014 by journals indexed in MEDLINE.Review of a representative sample of articles indexed in MEDLINE (n = 428) with observational design and use of MRMs (logistic, linear, and Cox regression). We assessed the quality of reporting about: model assumptions and goodness-of-fit, interactions, sensitivity analysis, crude and adjusted effect estimate, and specification of more than 1 adjusted model.The tests of underlying assumptions or goodness-of-fit of the MRMs used were described in 26.2% (95% CI: 22.0-30.3) of the articles and 18.5% (95% CI: 14.8 22.1) reported the interaction analysis. Reporting of all items assessed was higher in articles published in journals with a higher impact factor.A low percentage of articles indexed in MEDLINE that used multivariable techniques provided information demonstrating rigorous application of the model selected as an adjustment method. Given the importance of these methods to the final results and conclusions of observational studies, greater rigor is required in reporting the use of MRMs in the scientific literature. PMID- 27196468 TI - Comparison of Laparoscopy and Laparotomy in Surgical Staging of Apparent Early Ovarian Cancer: 13-year Experience. AB - The aim of this study was to compare the safety and morbidity of laparoscopic versus laparotomic comprehensive staging of apparent early stage ovarian cancer.In this retrospective study, the outcomes of patients with apparent stage I ovarian cancer who underwent laparoscopic or laparotomic comprehensive surgical staging from January 2002 to January 2014 were evaluated. The long-term survival of patients with early ovarian cancer was compared.Forty-two patients were treated by laparoscopy, and 50 were treated by laparotomy. The median operative time was 200 minutes in the laparoscopy group and 240 minutes in the laparotomy group (P >0.05). The median length of hospital stay was 3 days in the laparoscopy group and 7 days in the laparotomy group (P <0.05). Following laparoscopic and laparotomic staging, the cancer was upstaged for 9 (21.4%) and 10 (20.0%) women, respectively. The median follow-up time was 82 months in the laparoscopic and laparotomic groups, respectively. Excluding the upstaged patients, no recurrence was observed in the present study, and the overall survival and 5-year survival rates were 100% in both the laparoscopy and laparotomy groups.Laparoscopic and laparotomic comprehensive staging of early ovarian cancer were similar in terms of staging adequacy, accuracy and survival rate. Laparoscopic staging was associated with a significantly reduced hospital stay. Prospective randomized trials are required to evaluate the overall oncologic outcomes. PMID- 27196470 TI - Gonadotropin-Releasing Hormone Stimulate Aldosterone Production in a Subset of Aldosterone-Producing Adenoma. AB - We aimed to detect novel genes associated with G protein-coupled receptors (GPCRs) in aldosterone-producing adenoma (APA) and elucidate the mechanisms underlying aldosterone production.Microarray analysis targeting GPCR-associated genes was conducted using APA without known mutations (APA-WT) samples (n = 3) and APA with the KCNJ5 mutation (APA-KCNJ5; n = 3). Since gonadotropin-releasing hormone receptor (GNRHR) was the highest expression in APA-WT by microarray analysis, we investigated the effect of gonadotropin-releasing hormone (GnRH) stimulation on aldosterone production.The quantitative polymerase chain reaction assay results revealed higher GNRHR expression levels in APA-WT samples those in APA-KCNJ5 samples (P < 0.05). LHCGR levels were also significantly elevated in APA-WT samples, and there was a significant and positive correlation between GNRHR and LHCGR expression in all APA samples (r = 0.476, P < 0.05). Patients with APA-WT (n = 9), which showed higher GNRHR and LHCGR levels, had significantly higher GnRH-stimulated aldosterone response than those with APA KCNJ5 (n = 13) (P < 0.05). Multiple regression analysis revealed that the presence of the KCNJ5 mutation was linked to GNRHR mRNA expression (beta = 0.94 and P < 0.01). HAC15 cells with KCNJ5 gene carrying T158A mutation exhibited a significantly lower GNRHR expression than that in control cells (P < 0.05).We clarified increased expression of GNRHR and LHCGR in APA-WT, and the molecular analysis including the receptor expression associated with clinical findings of GnRH stimulation. PMID- 27196471 TI - Diagnosis and Treatment of Odontogenic Cutaneous Sinus Tracts in an 11-Year-Old Boy: A Case Report. AB - Odontogenic cutaneous sinus tracts (OCSTs) are generally primarily misdiagnosed and inappropriately treated by virtue of their rarity and the absence of dental symptoms. Accurate diagnosis and treatment and the elimination of the source of infection can reduce the incidence of complications and relieve the pain of the patient.In this case report, we present the case of an 11-year-old patient with an apparent abscess but an unobvious draining sinus tract in his left cheek. Intraorally, a glass-ionomer-cement filling on the occlusal surface of the left mandibular first molar (tooth 36) was noted. Radiographic examination revealed a radiopaque mass inside the crown and pulp chamber and an irregular, radiolucent periapical lesion surrounding the distal root apex. He was diagnosed with an OCTS secondary to a periapical abscess of tooth 36. Precise root canal therapy (RCT) and chronic granuloma debridement was performed; 6 months later, the abscess and sinus had healed completely, and the periapical lesion had resolved.Odontogenic cutaneous sinus tracts are uncommon in the clinic. This case report reminds us of the significance of OCSTs and provides some implications for their diagnosis and treatment. PMID- 27196469 TI - Comparison of Changes in Biochemical Markers for Skeletal Muscles, Hepatic Metabolism, and Renal Function after Three Types of Long-distance Running: Observational Study. AB - The purpose of this study is to compare changes in biochemical markers for the skeletal muscles, hepatic metabolism, and renal function based on extreme long distance running.Among healthy amateur endurance athletes who participated in a marathon, 100 km-, or 308 km ultramarathon, 15 athletes with similar physical and demographic characteristics were chosen to be the subjects in this study, upon completion of each course. The subjects' blood was collected before and after the course to identify biochemical markers for the skeletal muscles, hepatic metabolism, and renal function.After all of the courses, creatinine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine transaminase (ALT), blood urea nitrogen (BUN), and creatinine were found to be significantly increased compared with values obtained before the race (P <0.05 for each marker). CK, LDH, AST, and LDH were significantly higher after completion of the 100 km race than the marathon (P <0.05) and were significantly higher after the 308 km race than the marathon or 100 km race (P <0.05). Total protein was significantly lower after the 308 km race than the marathon or 100 km race (P <0.05). Albumin significantly increased after the marathon but significantly decreased after the 308 km course (P <0.05). Total and direct bilirubin were significantly increased after the 100 km and 308 km races (P <0.05), and were significantly higher after the 308 km than the marathon or 100 km course (P <0.05). BUN was significantly higher after the 100 km race than the marathon (P <0.05) and was significantly lower after the 308 km than the 100 km race (P <0.05). Creatinine was significantly higher after the marathon and 100 km than the 308 km race (P <0.05). Uric acid significantly increased after the marathon and 100 km race (P <0.05); it was significantly higher after completing the marathon and 100 km than the 308 km race (P <0.05).Muscular damage, decline in hepatic function, and hemolysis in the blood were higher after running a 308 km race, which is low-intensity running compared with a marathon, and a temporary decline in renal function was higher after completing a 100 km race, which is medium-to-high intensity. PMID- 27196473 TI - The Effect of Gabapentin on Acute Postoperative Pain in Patients Undergoing Total Knee Arthroplasty: A Meta-Analysis. AB - The purpose of this systematic review and meta-analysis of randomized controlled trials (RCTs) and non-RCTs was to evaluate the efficacy and safety of gabapentin versus placebo for pain control after total knee arthroplasty (TKA).In December 2015, a systematic computer-based search was conducted in the Medline, Embase, PubMed, Cochrane Controlled Trials Register (CENTRAL), Web of Science, Google, and Chinese Wanfang databases. This systematic review and meta-analysis were performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement criteria. The primary endpoint was the visual analogue scale (VAS) score after TKA with rest or mobilization at 24 and 48 hours, representing the efficacy of pain control after TKA. Cumulative morphine consumption via patient controlled anesthesia (PCA) was also assessed to determine the morphine-spare effect. Complications such as dizziness, pruritus, vomiting, nausea, and sedation were also compiled to assess the safety of gabapentin. Stata 12.0 software was used for the meta-analysis. After testing for publication bias and heterogeneity across studies, the data were aggregated for random-effects modeling whenever necessary.Six studies involving 769 patients met the inclusion criteria. Our meta-analysis revealed that gabapentin resulted in superior pain relief compared to the control group in terms of VAS score with rest at 24 hours (mean difference [MD] = -3.47; 95% confidence interval [CI] 6.16 to -0.77; P = 0.012) and at 48 hours postoperatively (MD = -2.25; 95% CI 4.21 to -0.30; P = 0.024). There was no statistically significant difference between the groups with respect to the VAS score at 24 hours postoperatively (MD = 1.05; 95% CI -3.31 to 5.42; P = 0.636) or at 48 hours (MD = 1.71; 95% CI -0.74 to 4.15; P = 0.171). These results indicated that the perioperative administration of gabapentin decreases the cumulative morphine consumption via PCA at 24 hours (MD = -8.28; 95% CI -12.57 to -3.99; P = 0.000) and 48 hours (MD = -4.50; 95% CI -10.98 to -3.61; P = 0.221). Furthermore, gabapentin decreased the rate of postoperative dizziness (relative risk [RR], 0.68; 95% CI 0.47-0.99, P = 0.044) and the occurrence of pruritus (RR, 0.50; 95% CI 0.37-0.67, P = 0.000).Based on the current meta-analysis, gabapentin exerts an analgesic and opioid-sparing effect in acute postoperative pain management without increasing the rate of dizziness and pruritus. PMID- 27196474 TI - Propofol-Based Sedation Versus General Anesthesia for Endoscopic Submucosal Dissection. AB - The main objective of this study is to evaluate general anesthesia or propofol based sedation methods at gastric endoscopic submucosal dissection (ESD) procedures.The anesthetic method administered to cases undergoing upper gastrointestinal ESD between 2013 and 2015 was retrospectively investigated. Procedure time, lesion size, dissection speed, anesthesia time, adverse effects such as gag reflex, nausea, vomiting, cough, number of desaturation episodes (SpO2 < 90%), oropharyngeal suctioning requirements, hemorrhage, perforation, and amount of anesthetic medications were recorded.There were 54 and 37 patients who were administered sedation (group S) and general anesthesia (group G), respectively. The demographics of the groups were similar. The calculated dissection speed was significantly high in group G (36.02 +/- 20.96 mm/min) compared with group S (26.04 +/- 17.56 mm/min; P = 0.010). The incidence of nausea, cough, number of oropharyngeal suctioning, and desaturation episodes were significantly high in group S compared with that in group G (P < 0.5). While there was no difference between the groups in terms of hemodynamic parameters, in group S the use of propofol and in group G the use of midazolam and fentanyl were significantly higher (P < 0.05). Anesthesia time, postoperative anesthesia care unit, and hospital stay durations were not significantly different between the groups.General anesthesia increased dissection speed and enhanced endoscopist performance when compared with propofol-based sedation technique. PMID- 27196472 TI - Functional Status Assessment of Patients With COPD: A Systematic Review of Performance-Based Measures and Patient-Reported Measures. AB - Presently, there is no recommendation on how to assess functional status of chronic obstructive pulmonary disease (COPD) patients. This study aimed to summarize and systematically evaluate these measures.Studies on measures of COPD patients' functional status published before the end of January 2015 were included using a search filters in PubMed and Web of Science, screening reference lists of all included studies, and cross-checking against some relevant reviews. After title, abstract, and main text screening, the remaining was appraised using the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) 4-point checklist. All measures from these studies were rated according to best-evidence synthesis and the best-rated measures were selected.A total of 6447 records were found and 102 studies were reviewed, suggesting 44 performance based measures and 14 patient-reported measures. The majority of the studies focused on internal consistency, reliability, and hypothesis testing, but only 21% of them employed good or excellent methodology. Their common weaknesses include lack of checks for unidimensionality, inadequate sample sizes, no prior hypotheses, and improper methods. On average, patient-reported measures perform better than performance-based measures. The best-rated patient-reported measures are functional performance inventory (FPI), functional performance inventory short form (FPI-SF), living with COPD questionnaire (LCOPD), COPD activity rating scale (CARS), University of Cincinnati dyspnea questionnaire (UCDQ), shortness of breath with daily activities (SOBDA), and short-form pulmonary functional status scale (PFSS-11), and the best-rated performance-based measures are exercise testing: 6-minute walk test (6MWT), endurance treadmill test, and usual 4-meter gait speed (usual 4MGS).Further research is needed to evaluate the reliability and validity of performance-based measures since present studies failed to provide convincing evidence. FPI, FPI-SF, LCOPD, CARS, UCDQ, SOBDA, PFSS-11, 6MWT, endurance treadmill test, and usual 4MGS performed well and are preferable to assess functional status of COPD patients. PMID- 27196475 TI - Income Disparities in the Use of Health Screening Services Among University Students in Korea: A Cross-Sectional Study of 2479 Participants in a University. AB - Public health insurance coverage for preventive care in young adults is incomplete in Korea. Few studies have focused on young adults' socioeconomic disparities in preventive care utilization. We aimed to explore household income disparities in the use of different types of health screening services among university students in Korea.This cross-sectional study used a web-based self administered survey of students at a university in Korea from January to February 2013. To examine the associations between household income levels and health screening service use within the past 2 years, odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression with adjustment for various covariables.Of 2479 participants, 45.5% reported using health screening services within 2 years (university-provided screening 32.9%, private sector screening 16.7%, and both 4.1%). Household income levels were not significantly associated with overall rates of health screening service use with a multivariable-adjusted OR (95% CI) in the lowest versus highest income group of 1.12 (0.87-1.45, Ptrend = 0.35). However, we found significantly different associations in specific types of utilized screening services by household income levels. The multivariable-adjusted OR (95% CI) of university-provided health screening service use in the lowest versus highest income level was 1.74 (1.30 2.34; Ptrend < 0.001), whereas the multivariable-adjusted OR (95% CI) of private sector service use in the lowest versus highest income level was 0.45 (0.31-0.66; Ptrend < 0.001).This study demonstrated significant disparities in the types of utilized health screening services by income groups among university students in Korea, although overall rates of health screening service use were similar across income levels. Low-income students were more likely to use university-provided health screening services, and less likely to use private sector screening services. To ensure appropriate preventive care delivery for young adults and to address disparities in disadvantaged groups, the expansion of medical insurance coverage for preventive health care, establishment of a usual source of care, focusing on vulnerable groups, and the development of evidence-based standardized health screening guidelines for young adults are needed. PMID- 27196476 TI - Finger Fractures as an Early Manifestation of Primary Hyperparathyroidism Among Young Patients: A Case Report of a 30-Year-Old Male With Recurrent Osteoporotic Fractures. AB - Osteoporosis and osteoporotic fractures represent a substantial health burden, and predominantly affect the elderly. Younger generations may also develop these conditions because of various predisposing conditions, including primary hyperparathyroidism. However, little information is available regarding early skeletal manifestations of primary hyperparathyroidism.A 30-year-old Japanese male presented with pain in his left wrist, and was diagnosed with a distal radius fracture. During surgery, we noticed decreased bone strength of the fracture site. Further investigation found osteoporosis and primary hyperparathyroidism owing to a solitary parathyroid adenoma, which was resected without significant complications. History revealed that the patient suffered a metacarpal bone fracture of his right fifth bone 6 months earlier. Although serial x-rays at that time had shown rapidly developed cortical bone erosion around the fractured finger, the possibility of primary hyperparathyroidism was overlooked because of poor awareness of the condition, leading to a 6-month delay in the diagnosis of primary hyperparathyroidism.Clinicians should be aware that finger fractures may be an early skeletal manifestation of primary hyperparathyroidism that can help achieve a prompt diagnosis of the condition, especially when they occur in young adults in the absence of major trauma. PMID- 27196479 TI - New Perspectives on Criteria for the Determination of HCG Trigger Timing in GnRH Antagonist Cycles. AB - The aim of this study was to investigate 2 quantification criteria to evaluate the developmental condition of follicles cohort and clarify their impacts upon the determining of human chorionic gonadotropin trigger timing and the reproductive outcome: the proportion of mature follicles in growing follicles cohort on the day of human chorionic gonadotropin trigger and the peak estradiol level per oocyte on the day of human chorionic gonadotropin administration.Of the patients who underwent in vitro fertilization/ intracytoplasmic sperm injection embryo transfer from 2011 to 2013, 492 controlled ovarian hyperstimulation cycles using gonadotropin-releasing hormone antagonists reaching the ovum pick-up and fresh embryo-transfer stage were included. Patients were divided into 3 groups according to their >=17 mm/>=10 mm follicles ratio on the day of human chorionic gonadotropin administration (Low proportion: <=30%, Middle proportion: 30%-60%, High proportion: >=60%). Patients were divided into 5 groups according to their peak estradiol level/oocyte (Group A: <100 pg/mL per oocyte, Group B: 100-199 pg/mL per oocyte, Group C: 200-299 pg/mL per oocyte, Group D: 300-399 pg/mL per oocyte, Group E >=400 pg/mL per oocyte) as well. Comparison among groups was made regarding ovarian stimulation characteristics, fertilization rate, good quality embryo rate, implantation, pregnancy, and live birth rates.On the basis of >=17 mm/>=10 mm follicles ratio, the number of oocyte retrieved in low proportion group is more than other 2 groups. Implantation rate, clinical pregnancy, and live birth rate in high proportion group were 25.8%, 42.7%, and 31.1%, respectively, which is highest in 3 groups, and statistical significance existed between high and middle proportion groups. When the division is based on peak estradiol level/oocyte, the number of oocyte retrieved of >=400 pg/mL per oocyte Group was significantly lowest compared with the other 4 groups. Matured ovum rate, fertilization rate, and good quality embryos rate exhibited an increasing trend as the peak estradiol level/oocyte increased. While pregnancy rate, implantation rate, and live birth rate were found to be lower whenever estradiol/oocyte ratio exceeded 400 pg/mL per oocyte or less than 100 pg/mL per oocyte, and there is statistical difference.Patients with the proportion of mature follicle reaching 60% on the day of human chorionic gonadotropin trigger and peak estradiol/oocyte level within 100~399 pg/mL range can get a better pregnancy and implantation rate. PMID- 27196477 TI - Simple Prediction Model of Axillary Lymph Node Positivity After Analyzing Molecular and Clinical Factors in Early Breast Cancer. AB - The aim of this study was to evaluate the association between pretreatment molecular and clinical factors and axillary lymph node metastases in early breast cancer. A total of 367 consecutive breast cancer patients with cT1-2NxM0 who underwent breast conserving surgery and axillary lymph node dissection followed by whole breast irradiation were enrolled. We evaluated the pathologic tumor and node status, tumor differentiation, calcification, and lymphovascular invasion, the status of estrogen receptor (ER), progesterone receptor (PR), epidermal growth factor receptor 1 (EGFR1), and human epidermal growth factor receptor 2 (HER2), the expression of E-cadherin, P53, and Ki-67 index. Totally, 108 (29.4%) of the 367 patients had positive axillary lymph nodes. An increased tumor size (P = 0.024), the presence of lymphovascular invasion (P < 0.001), and Ki-67 index of >20% (P = 0.038) were significantly associated with axillary lymph node metastases on the multivariate analysis. In our study, 86.2% of the patients with all the unfavorable factors had an involvement of axillary nodal metastases, and only 12.2% of the patients with all the favorable predictors had positive axillary nodes. The predictive power was significant on the receiver operating curve (P < 0.001). We found that several factors, such as tumor size, lymphovascular invasion, and the Ki-67 index, are independent factors that predict positive ALNM on multivariate analysis for the patients with cT1-2 breast cancer. Clinicians simply could predict the probability of ALNM after verifying the molecular and clinical factors in early breast cancer. PMID- 27196478 TI - Calcifying Fibrous Tumor: Review of 157 Patients Reported in International Literature. AB - Calcifying fibrous tumor (CFT) is a benign lesion characterized by its specific histological findings and is found as solitary or multiple lesions in several locations of the human body. The aim of the present systematic review is to give a detailed account of all reported cases of CFT in the literature and to analyze the available data, to completely characterize the entity from epidemiological, medical, and surgical aspects.A bibliographic research was performed from 1988 until 2015. A database with the patients' characteristics was made, including sex, age, location of the tumor, symptoms, symptoms duration, size of the tumor, diagnostic methods, treatment, metastasis, and follow-up.A total of 104 articles were identified, reporting 157 cases of CFT. Mean age of patients was 33.58 years and the ratio between men and women was 1:1.27. The most common locations of CFT were stomach (18%), small intestine (8.7%), pleura (9.9%), mesentery (5%), and peritoneum (6.8%). Mean diameter of the tumor was estimated 4.6 cm. The correlations proceeded showed that as age increases, size decreases (P = 0.001) and that the tumor is larger in females (P = 0.027). Kruskal-Wallis test showed that the larger tumors appear in the neck and adrenal gland (P = 0.001). The percentage of asymptomatic patients was 30.57%. Computed tomography and biopsy were the most common tests for the diagnosis of CFT. Open surgical procedure was performed in the majority of cases. The median hospitalization was 6.06 days and the mean follow-up period was 29.97 months. Recurrences were mentioned in 10 of 96 patients with available data. No deaths owing to CFT were mentioned in the literature.CFT should be included in the differential diagnosis of enlarging mass revealed by clinical or imaging examination either incidentally or after specific acute or chronic symptomatology. PMID- 27196480 TI - Bacteremic Urinary Tract Infection Caused by Multidrug-Resistant Enterobacteriaceae Are Associated With Severe Sepsis at Admission: Implication for Empirical Therapy. AB - The purpose of this study is to compare the clinical features and treatment outcomes among patients with bacteremic urinary tract infection (UTI) caused by multidrug-resistant (MDR) and non-MDR Enterobacteriaceae and to identify whether MDR pathogens were independently associated with severe sepsis or septic shock at presentation.The clinical data of adult patients visiting and being treated at Chia-Yi Christian Hospital due to bacteremic UTI caused by Enterobacteriaceae from January 2006 to August 2015 were retrospectively analyzed.A total of 585 patients were enrolled. Among them, 220 (37.6%) were caused by the MDR Enterobacteriaceae. A total of 206 patients (35.2%) developed severe sepsis or septic shock at presentation. Patients in the MDR group tend to be male and have a past history of gout, recurrent UTI, prior hospitalization, hydronephrosis, renal stone, ureteral stone, indwelling urinary catheter, newly development of renal dysfunction, severe sepsis or septic shock, intensive care unit (ICU) admission, receipt of ineffective empirical therapy, longer hospital stay, and higher in-hospital mortality (2.7% vs 1.9%, P = 0.569). Using multivariate logistic regression analysis, it is revealed that independent predictors associated with severe sepsis or septic shock at presentation were liver cirrhosis (OR 2.868; 95% CI 1.439-5.716; P = 0.003), indwelling urinary catheter (OR 1.936; 95% CI 1.238-3.027; P = 0.004), and MDR Enterobacteriaceae (OR 1.447; 95% CI 1.002-2.090; P = 0.049).Multidrug resistance was associated with the development of severe sepsis or septic shock upon presentation among patients with bacteremic UTI caused by Enterobacteriaceae. Therefore, empirical antibiotics therapy for patients with UTI presented with severe sepsis and/or septic shock should be more broad-spectrum to effectively cover MDR Enterobacteriaceae. PMID- 27196482 TI - Risk Factors for Esophageal Fistula Associated With Chemoradiotherapy for Locally Advanced Unresectable Esophageal Cancer: A Supplementary Analysis of JCOG0303. AB - Esophageal fistula is a critical adverse event in patients treated with chemoradiotherapy (CRT) for locally advanced esophageal cancer. However, risk factors associated with esophageal fistula formation in patients receiving CRT have not yet been elucidated.We retrospectively analyzed data obtained from 140 patients who were enrolled in a phase II/III trial comparing low-dose cisplatin with standard-dose cisplatin administered in combination with 5-flurouracil and concomitant radiotherapy. Inclusion criteria were performance status (PS) 0 to 2 and histologically proven thoracic esophageal cancer clinically diagnosed as T4 and/or unresectable lymph node metastasis for which definitive CRT was applicable. Risk factors for esophageal fistula were examined with univariate analysis using Fisher exact test and multivariate analysis using logistic regression models.Esophageal fistula was observed in 31 patients (22%). Of these, 6 patients developed fistula during CRT. Median time interval between the date of CRT initiation and that of fistula diagnosis was 100 days (inter quartile range, 45-171). Esophageal stenosis was the only significant risk factor for esophageal fistula formation both in univariate (P = 0.026) and in multivariate analyses (odds ratio, 2.59; 95% confidence interval, 1.13-5.92, P = 0.025). Other clinicopathological factors, namely treatment arm, age, sex, PS, primary tumor location, T stage, lymph node invasion to adjacent organs, blood cell count, albumin level, and body mass index, were not risk factors fistula formation.Esophageal stenosis was a significant risk factor for esophageal fistula formation in patients treated with CRT for unresectable locally advanced thoracic esophageal squamous cell carcinoma. PMID- 27196481 TI - Erdheim-Chester Disease With Multiorgan Involvement, Following Polycythemia Vera: A Case Report. AB - Erdheim-Chester disease is a rare form of non-Langerhans cell histiocytosis characterized by the migration and infiltration of lipid-laden CD68, CD1a and S100 histiocytes to various target organs, which leads to the disruption of physiological tissue architecture and reactive fibrosis, and thus impairs organ function.We describe the first case of a patient with Erdheim-Chester disease with multiorgan involvement developed after 6 years from polycythemia vera diagnosis. During the follow-up, an abdominal ultrasound scan revealed the presence of dense, bilateral perinephric infiltration. A computed tomographic guided core biopsy was performed in order to identify the histological nature of this lesion, and a morphological analysis demonstrated the accumulation of foamy histiocytes surrounded by fibrosis. The BRAFV600E mutation was detected, and a diagnosis of Erdheim-Chester disease was made.The extreme rarity of Erdheim Chester disease strongly suggests the existence of potentially common element(s) that may have contributed to the pathogenesis of both disorders. Obviously, further studies are needed to clarify the mutual roles and effects of JAK2 and BRAF mutations in this patient, as well as their possible therapeutic implications. PMID- 27196484 TI - Chinese Herbal Medicine and Salmeterol and Fluticasone Propionate for Chronic Obstructive Pulmonary Disease: Systematic Review and Network Meta-Analysis. AB - Among Chinese populations worldwide, Chinese herbal medicines (CHMs) are often used as an adjunct to pharmacotherapy in managing chronic obstructive pulmonary disease (COPD). However, the relative performance among different CHM is unknown.The aim of this study was to evaluate comparative effectiveness of different CHM when used with salmeterol and fluticasone propionate (SFP), compared with SFP alone.This study is a systematic review of randomized controlled trials (RCTs) with network meta-analyses (NMAs).Eight electronic databases were searched. Data from RCTs were extracted for random effect pairwise meta-analyses. Pooled relative risk (RR) with 95% confidence interval (CI) was used to quantify the impact of CHM and SFP on forced expiratory volume in 1 second (FEV1), St George's Respiratory Questionnaire (SGRQ) scoring, and 6-Minute Walk Test (6MWT). NMA was used to explore the most effective CHM when used with SFP.Eleven RCTs (n = 925) assessing 11 different CHM were included. Result from pairwise meta-analyses indicated favorable, clinically relevant benefit of CHM and SFP on FEV1 [7 studies, pooled weighted mean difference (WMD) = 0.20 L, 95% CI: 0.06-0.34 L], SGRQ scoring (5 studies, pooled WMD = -4.99, 95% CI: -7.73 to 2.24), and 6MWT (3 studies, pooled WMD = 32.84 m, 95% CI: 18.26-47.42). Results from NMA showed no differences on the comparative effectiveness among CHM formulations for improving FEV1. For SGRQ, NMA suggested that Runfeijianpibushen decoction and Renshenbufei pills performed best. Use of CHM on top of SFP can provide clinically relevant benefit for COPD patients on FEV1 and SGRQ. Additional use of Runfeijianpibushen decoction and Renshenbufei pills showed better effect on improving SGRQ.Use of CHM and SFP may provide clinically relevant benefit for COPD patients on FEV1, SGRQ, and 6MWT. Use of different CHM formulae included in this NMA showed similar effect for increasing FEV1, while the additional use of Runfeijianpibushen formula and Renshenbufei Pills showed better effect on improving SGRQ. Well conducted, adequately powered trials are needed to confirm their effectiveness in the future. PMID- 27196483 TI - Evaluation of an Association of Blood Homocysteine Levels With Gastric Cancer Risk From 27 Case-Control Studies. AB - High blood homocysteine levels may risk gastric cancer. However, observational studies have been plagued by chance, bias, confounding, or reverse causality. In this study, we assessed the relationship between blood homocysteine levels and gastric cancer by using a Mendelian randomization method, which is independent of nongenetic confounding.We took 2 steps to perform Mendelian randomization analysis. First, we evaluated the methylenetetrahydrofolate reductase (MTHFR) C677T association with gastric cancer by a meta-analysis of case-control studies including 7566 patients with gastric cancer and 10 640 control subjects from 27 Case-Control studies. Second, MTHFR C677T polymorphism, which affects the blood homocysteine levels, was used as an instrumental variable to calculate the risk and estimate the association of gastric cancer with this single nucleotide polymorphism (SNP). We obtained an estimate to the association of blood total homocysteine levels with this SNP from a meta-analysis of Genome-Wide Association Studies (GWAS), which comprises a total of 44 147 individuals.In our Mendelian randomization analysis, we demonstrated a significant effect of the blood homocysteine levels on gastric cancer risk, representing an OR of 2.56 (95% CI = 2.41-2.72; P = 5.0*10) for gastric cancer per 1-SD increase in the natural log transformed blood total homocysteine levels.We proved that there is a causal relationship between blood total homocysteine and risk of gastric cancer, and this study will add insight into the treatment and pathology research of gastric cancer. PMID- 27196485 TI - Preventive Analgesic Efficacy of Nefopam in Acute and Chronic Pain After Breast Cancer Surgery: A Prospective, Double-Blind, and Randomized Trial. AB - Breast cancer surgery is known to cause severe acute postoperative pain, which can persist for a long time. We administered nefopam preventively to patients undergoing lumpectomy with axillary lymph node dissection or sentinel lymph node biopsy, and evaluated its efficacy on acute and chronic postoperative pain.Enrolled patients were assigned to the nefopam (n = 41) or the control (n = 42) group. Before initiating the operation, 20 mg of nefopam was given to the patients of the nefopam group, and normal saline was used in the control group. Ketorolac was given at the end of surgery, and meloxicam was prescribed in the postoperative period to all patients in both groups. Pain was assessed using a numerical rating scale (NRS), and the rescue analgesic drug was given when the NRS was >5. Implementation of postoperative chemotherapy, radiotherapy (RT), or hormone therapy was evaluated.The NRS of postoperative pain was significantly lower in the nefopam than in the control group in the postanesthetic care unit (4.5 +/- 2.2 vs 5.7 +/- 1.5, respectively; P = 0.01), at postoperative 6 h (3.0 +/- 1.6 vs 4.5 +/- 1.3, respectively; P < 0.001), and at postoperative 24 h (3.1 +/- 1.1 vs 3.8 +/- 1.5, respectively; P = 0.01) with reduced use of rescue analgesic drugs. Significantly fewer patients suffered from chronic postoperative pain in the nefopam than in the control group at postoperative 3 months (36.6% vs 59.5%, P = 0.04). Considering only the cohort without postoperative adjuvant RT, the difference in the proportion of patients reporting chronic pain increased (23.5% in the nefopam group vs 61.5% in the control group, P = 0.04).Preventive nefopam was helpful in reducing the acute postoperative pain, with reduced use of rescue analgesic drugs, and it contributed to reduced occurrence of chronic pain at postoperative 3 months after breast cancer surgery. PMID- 27196486 TI - FTO rs 9939609 SNP Is Associated With Adiponectin and Leptin Levels and the Risk of Obesity in a Cohort of Romanian Children Population. AB - Obesity is a disorder with increasing frequency in children and adolescents, directly linked with various diseases. Variants in the FTO (fat mass and obesity related) gene have been associated with body mass index and waist and hip circumferences in widespread populations.The aim of this case-control study was to assess if there is any association between FTO gene variants rs9939609, respectively, rs17817449 with anthropometric and metabolic biomarkers (fasting glucose, TC, HDL-cholesterol, LDL-cholesterol, triglycerides) and adipokines (adiponectin and leptin), in Romanian obese children.A total of 387 children, 201 obese and 186 nonobese individuals, were included in this prospective study. Genotyping of the FTO gene polymorphisms for all subjects was performed using the restriction fragment length polymorphism (PCR-RFLP) method.Significant associations were found between FTO rs9939609 single nucleotide polymorphism (SNP) and obesity. AA genotype carriers have a 2.02 times higher risk for obesity compared with AT+TT genotype carriers. Risk allele carriers of rs17817449 SNP had somewhat higher values of weight, body mass index, waist and hip circumference, total cholesterol, triglycerides, adiponectin, and fasting glucose.This study revealed the genetic association between rs9939609 SNP of FTO and obesity in a Romanian population, and to the authors' knowledge, this is the first study to investigate this association in a Romanian population. This study also established that combined variant genotypes (AA/GG) of FTO rs9939609 /rs17817449 are strongly associated with several measures of adiposity (weight, BMI-SD, mid upper arm circumference, tricipital skinfold thicknesses) and are also associated with total cholesterol, triglyceride, and LDL-cholesterol levels. PMID- 27196487 TI - Local Immune Response in Helicobacter pylori Infection. AB - There have been few studies concerning the cytokine profiles in gastric mucosa of Helicobacter pylori-infected patients with normal mucosa, chronic gastritis, and gastric carcinoma (GAC).In the present study, we aimed to elucidate the genomic expression levels and immune pathological roles of cytokines-interferon (IFN) gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-4, IL-6, IL-10, transforming growth factor (TGF)-beta, IL-17A, IL-32-in H pylori-infected patients with normal gastric mucosa (NGM; control), chronic active gastritis (CAG), and GAC. Genomic expression levels of these cytokines were assayed by real time PCR analysis in gastric biopsy specimens obtained from 93 patients.We found that the genomic expression levels of IFN-gamma, TNF-alpha, IL-6, IL-10, IL-17A mRNA were increased in the CAG group and those of TNF-alpha, IL-6, IL-10, IL-17A, TGF-beta mRNA were increased in the GAC group with reference to H pylori-infected NGM group.This study is on the interest of cytokine profiles in gastric mucosa among individuals with normal, gastritis, or GAC. Our findings suggest that the immune response of gastric mucosa to infection of H pylori differs from patient to patient. For individual therapy, levels of genomic expression of IL-6 or other cytokines may be tracked in patients. PMID- 27196488 TI - Inter- and Intradigit Somatotopic Map of High-Frequency Vibration Stimulations in Human Primary Somatosensory Cortex. AB - Although more about the somatotopic mapping of fingers continues to be uncovered, there is lack of mapping attempts regarding the integration of within-finger and across-finger somatotopic coordinates in Broadmann area (BA) 3. This study aimed to address the issue by finding an inter-/intradigit somatotopic map with high frequency (250 Hz) vibrotactile stimulation. Functional magnetic resonance imaging (fMRI) data were acquired while stimulation was applied to 3 phalanxes (distal [p1], intermediate [p2], and proximal [p3] phalanx) of 4 fingers (index, middle, ring, and little finger) for a total of 12 finger-phalanx combinations for a human. Inter-, intra-, and inter-/intradigit distances were calculated from peak activation coordinates in BA 3 for each combination. With regard to interdigit dimensions, the somatotopic coordinates proceeded in the lateral-to medial direction for the index, middle, ring, and little fingers consecutively. This trend is comparable to that generated from low-frequency stimulation modalities (flutter stimulation). The somatotopic distances between fingers were greatest when p1 was compared across fingers. From an intradigit perspective, stimulation on p1, p2, and p3 yielded BA 3 peak coordinates aligned along the anterior-to-posterior and inferior-to-superior directions for all fingers. An inter-/intradigit map exhibited a radially propagating trend of distances calculated with respect to index p1 as a reference point; this provided an integrated view of inter- and intradigit somatotopies, which are traditionally discussed separately. We expect such an inter-/intradigit somatotopic map approach to contribute in generating a comprehensive somatotopic model of fingers. PMID- 27196489 TI - Notch Signaling Components: Diverging Prognostic Indicators in Lung Adenocarcinoma. AB - Non-small-cell lung cancer (NSCLC) is a lethal and aggressive malignancy. Currently, the identities of prognostic and predictive makers of NSCLC have not been fully established. Dysregulated Notch signaling has been implicated in many human malignancies, including NSCLC. However, the prognostic value of measuring Notch signaling and the utility of developing Notch-targeted therapies in NSCLC remain inconclusive. The present study investigated the association of individual Notch receptor and ligand levels with lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC) prognosis using the Kaplan-Meier plotte database. This online database encompasses 2437 lung cancer samples. Hazard ratios with 95% confidence intervals were calculated. The results showed that higher Notch1, Notch2, JAG1, and DLL1 mRNA expression predicted better overall survival (OS) in lung ADC, but showed no significance in SCC patients. Elevated Notch3, JAG2, and DLL3 mRNA expression was associated with poor OS of ADC patients, but not in SCC patients. There was no association between Notch4 and OS in either lung ADC or SCC patients. In conclusion, the set of Notch1, Notch2, JAG1, DLL1 and that of Notch3, JAG2, DLL3 played opposing prognostic roles in lung ADC patients. Neither set of Notch receptors and ligands was indicative of lung SCC prognosis. Notch signaling could serve as promising marker to predict outcomes in lung ADC patients. The distinct features of lung cancer subtypes and Notch components should be considered when developing future Notch-targeted therapies. PMID- 27196490 TI - Oncologic Safety of Local Excision Compared With Total Mesorectal Excision for ypT0-T1 Rectal Cancer: A Propensity Score Analysis. AB - Good oncologic outcomes, demonstrated by a complete pathologic response after preoperative chemoradiotherapy (PCRT), have led to local excision (LE) in selected patients with rectal cancer. We evaluated the oncologic safety of LE compared with total mesorectal excision (TME) in patients with ypT0-T1 rectal cancer.A retrospective review of 304 patients who underwent PCRT, followed by LE or TME, for ypT0-T1 rectal cancer was performed. Propensity scores were computed and used to match groups (LE:TME = 1:1), and analysis of disease-free survival (DFS) and overall survival (OS) was made by comparing patients who underwent LE or TME. Prognostic factors of relapse were analyzed for all patients.Tumor categories were ypT0 in 25 (61.9%) cases, ypTis in 6 (14.3%) cases, and ypT1 in 11 (26.2%) cases for the LE group, and ypT0 in 28 (66.7%) cases, ypTis in 4 (9.5%) cases, and ypT1 in 10 (23.8%) cases for the matched TME patients. There was no significant difference between the matched LE and TME groups in relapse (4.8% and 7.14%, respectively; P = 0.646), 5-year DFS (95.2% vs 91.6%; P = 0.33) and 5-year OS (96.6% vs 88.0%; P = 0.238). In the multivariate Cox regression analysis, tumor distance from the anal verge (hazard ratio [HR] = 0.78; 95% confidence interval (CI) = 0.616-0.992) and the tumor grade (HR = 4.29; 95% CI = 1.430-12.886) were significantly associated with the recurrence risk.LE results in oncologic outcomes that are comparable to those achieved by TME in selected patients with ypT0-T1 rectal cancer after PCRT. PMID- 27196491 TI - Angiotensin-Receptor Blocker, Angiotensin-Converting Enzyme Inhibitor, and Risks of Atrial Fibrillation: A Nationwide Cohort Study. AB - Both angiotensin-receptor blockers (ARB) and angiotensin-converting enzyme inhibitors (ACEI) have protective effects against atrial fibrillation (AF). The differences between ARB and ACEI in their effects on the primary prevention of AF remain unclear. This study compared ARB and ACEI in combined antihypertensive medications for reducing the risk of AF in patients with hypertension, and determined which was better for AF prevention in a nationwide cohort study.Patients aged >=55 years and with a history of hypertension were identified from Taiwan National Health Insurance Research Database. Medical records of 25,075 patients were obtained, and included 6205 who used ARB, 8034 who used ACEI, and 10,836 nonusers (no ARB or ACEI) in their antihypertensive regimen. Cox regression models were applied to estimate the hazard ratio (HR) for new-onset AF.During an average of 7.7 years' follow-up, 1619 patients developed new-onset AF. Both ARB (adjusted HR: 0.51, 95% CI 0.44-0.58, P < 0.001) and ACEI (adjusted HR: 0.53, 95% CI 0.47-0.59, P < 0.001) reduced the risk of AF compared to nonusers. Subgroup analysis showed that ARB and ACEI were equally effective in preventing new-onset AF regardless of age, gender, the presence of heart failure, diabetes, and vascular disease, except for those with prior stroke or transient ischemic attack (TIA). ARB prevents new-onset AF better than ACEI in patients with a history of stroke or TIA (log-rank P = 0.012).Both ARB and ACEI reduce new onset AF in patients with hypertension. ARB prevents AF better than ACEI in patients with a history of prior stroke or TIA. PMID- 27196492 TI - Conversion Chemotherapy for Technically Unresectable Colorectal Liver Metastases: A Retrospective, STROBE-Compliant, Single-Center Study Comparing Chemotherapy Alone and Combination Chemotherapy With Cetuximab or Bevacizumab. AB - The response rate of patients with unresectable liver-limited metastases of colorectal cancer can be improved by converting inoperable disease to operable disease. However, the benefits of conversion chemotherapy for survival are still controversial.Patients considered to have technically inoperable disease by a multidisciplinary team were retrospectively analyzed. Patients were stratified based on the treatment they received, into the chemotherapy only (G1), chemotherapy plus bevacizumab (G2), or chemotherapy plus cetuximab (G3) groups. The primary endpoint was the resection rate. The secondary endpoint was the overall survival (OS), according to both the treatment received and liver surgery status.In total, 104 patients were included: 30 in the G1, 39 in the G2, and 35 in the G3 groups. All G3 patients had the wild-type KRAS exon 2. The surgical resection rates for patients in the G1, G2, and G3 groups were 43.3% (13/30), 30.7% (12/39), and 51.4% (18/35), respectively. Disease-free survival did not show significant differences among the 3 groups. The median OS was 35.2 months in the G1, 28.8 months in the G2, and 42.1 months in the G3 (P = 0.25) groups. The OS was significantly higher in patients who underwent surgical resection than those who did not. The median OS was 28.4 months in patients who did not undergo resection, whereas it had not been reached after a median follow-up period of 37.5 months for patients who underwent surgical resection (events: 21/43).Our data confirmed that the conversion of initially inoperable disease to operable disease conferred a survival benefit, even in patients who relapsed after surgery. The addition of cetuximab to chemotherapy improved the objective response and resection rates, conferring a potential survival benefit even in patients whose diseases were not converted to operable disease, compared to chemotherapy alone or in combination with bevacizumab. PMID- 27196493 TI - A Randomized Cadaver Study Comparing First-Attempt Success Between Tibial and Humeral Intraosseous Insertions Using NIO Device by Paramedics: A Preliminary Investigation. AB - Medical personnel may encounter difficulties in obtaining intravenous (IV) access during cardiac arrest. The 2015 American Heart Association guidelines and the 2015 European Resuscitation Council guidelines for cardiopulmonary resuscitation (CPR) suggest that rescuers establish intraosseous (IO) access if an IV line is not easily obtainable.The aim of the study was to compare the success rates of the IO proximal tibia and proximal humerus head access performed by paramedics using the New Intraosseous access device (NIO; Persys Medical, Houston, TX, USA) in an adult cadaver model during simulated CPR.In an interventional, randomized, crossover, single-center cadaver study, a semi-automatic spring-load driven NIO access device was investigated. In total, 84 paramedics with less than 5-year experience in Emergency Medical Service participated in the study. The trial was performed on 42 adult cadavers. In each cadaver, 2 IO accesses to the humerus head, and 2 IO accesses to the proximal tibia were obtained.The success rate of the first IO attempt was 89.3% (75/84) for tibial access, and 73.8% (62/84) for humeral access (P = 0.017). The procedure times were significantly faster for tibial access [16.8 (interquartile range, IQR, 15.1-19.9] s] than humeral access [26.7 (IQR, 22.1-30.9) s] (P < 0.001).Tibial IO access is easier and faster to put in place than humeral IO access. Humeral IO access can be an alternative method to tibial IO access. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02700867. PMID- 27196494 TI - Renal Function and All-Cause Mortality Risk Among Cancer Patients. AB - Renal dysfunction predicts all-cause mortality in general population. However, the prevalence of renal insufficiency and its relationship with mortality in cancer patients are unclear.We retrospectively studied 9465 patients with newly diagnosed cancer from January 2010 to December 2010. Renal insufficiency was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m using the Chronic Kidney Disease Epidemiology Collaboration equation. The hazard ratio (HR) of all-cause mortality associated with baseline eGFR was assessed by Cox regression.Three thousand sixty-nine patients (32.4%) exhibited eGFR <90 mL/min/1.73 m and 3% had abnormal serum creatinine levels at the time of diagnosis. Over a median follow-up of 40.5 months, 2705 patients (28.6%) died. Compared with the reference group (eGFR >= 60 mL/min/1.73 m), an elevated all cause mortality was observed among patients with eGFR < 60 mL/min/1.73 m stratified by cancer stage in the entire cohort, the corresponding hazard ratios were 1.87 (95% CI, 1.41-2.47) and 1.28 (95% CI, 1.01-1.62) for stage I to III and stage IV, respectively. However, this relationship was not observed after multivariate adjustment. Subgroup analysis found that eGFR < 60 mL/min/1.73 m independently predicted death among patients with hematologic (adjusted HR 2.93, 95% CI [1.36-6.31]) and gynecological cancer (adjusted HR 2.82, 95% CI [1.19 6.70]), but not in those with other cancer. Five hundred fifty-seven patients (6%) had proteinuria. When controlled for potential confounding factors, proteinuria was a risk factor for all-cause mortality among patients in the entire cohort, regardless of cancer stage and eGFR values. When patients were categorized by specific cancer type, the risk of all-cause death was only significant in patients with digestive system cancer (adjusted HR, 1.85 [1.48 2.32]).The prevalence of renal dysfunction was common in patients with newly diagnosed cancer. Patients with eGFR < 60 mL/min/1.73 m or proteinuria were associated with increased risk for all-cause mortality, this relation depended on cancer site. PMID- 27196495 TI - Pregnancy Incidence in Female Nasopharyngeal Carcinoma Survivors of Reproductive Age: A Population-Based Study. AB - This study evaluated the pregnancy incidence in female nasopharyngeal carcinoma (NPC) survivors of reproductive age.In a nationwide cohort, 2816 female patients 15 to 50 years of age from 1998 to 2010 were identified from the Taiwan National Health Insurance Research database. Comorbidities, complications during pregnancy, and delivery status were recorded. All patients were followed up until a diagnosis of pregnancy, withdrawal from the National Health Insurance system, or December 31, 2011.Overall, 155 patients (incidence rate [IR] = 9.50) were pregnant in the NPC group, whereas 251 patients (IR = 12.80) were pregnant in the non-NPC group. The cumulative incidence of pregnancy in the NPC group was lower than that in the non-NPC group (incidence rate ratio = 0.74, 95% CI = 0.61-0.91). The adjusted hazard ratio of pregnancy in the NPC group was 0.79 with 95% CI = 0.61-0.96, compared with the non-NPC group.The incidence of pregnancy is significantly lower among female NPC survivors of reproductive age than among those without NPC. PMID- 27196496 TI - Increased Risk of Intracranial Hemorrhage in Patients With Pregnancy-Induced Hypertension: A Nationwide Population-Based Retrospective Cohort Study. AB - Pregnancy-induced hypertension (PIH) may be a major predictor of pregnancy associated intracranial hemorrhage (ICH). However, the relationship between PIH and long-term ICH risk is unknown.The objective of the study was to determine the association between PIH and ICH and to identify the predictive risk factors.Patients with newly diagnosed PIH were recruited from the Taiwan National Health Insurance Research Database. PIH patients were divided into gestational hypertension (GH) and preeclampsia groups. The 2 groups were separately compared with matched cohorts of patients without PIH based on age and date of delivery. The occurrence of ICH was evaluated in both cohorts. The overall observational period was from January 1, 2000 to December 31, 2013.Among the 23.3 million individuals registered in the National Health Insurance Research Database, 28,346 PIH patients, including 7390 with GH and 20,956 with preeclampsia, were identified. The incidences of ICH were increased in both groups (incidence rate ratio [IRR] = 3.72 in the GH group, 95% confidence interval [CI] 3.63-3.81, P < 0.0001 and IRR = 8.21 in the preeclampsia group, 95% CI 8.12-8.31, P < 0.0001, respectively). In addition, according to the results of stratification of follow up years, both groups were associated with a highest risk of ICH at 1 to 5 years of follow-up (IRR = 11.99, 95% CI 11.16-12.88, P < 0.0001 and IRR = 21.83, 95% CI 21.24-22.44, P < 0.0001, respectively). After adjusting for age, parity, severity of PIH, number of PIH occurrences, gestational age, and comorbidities in the multivariate survival analysis using Cox regression model, age >=30 years (hazard ratio [HR] 1.99, 95% CI 1.27-3.10, P = 0.0026), patients with preeclampsia (HR 2.18, 95% CI 1.22-3.90, P = 0.0089), multiple PIH occurrences (HR 4.08, 95% CI 1.85-9.01, P = 0.0005), hypertension (HR 4.51, 95% CI 1.89-10.74, P = 0.0007), and obesity (HR 7.21, 95% CI 1.58-32.84, P = 0.0107) were independent risk factors for the development of ICH among patients with PIH.Patients with PIH, especially those with older age, preeclampsia, and multiple PIH occurrences, may have an increased risk of developing ICH later in life. PMID- 27196497 TI - Periodontal Treatment Reduces Risk of Adverse Respiratory Events in Patients With Chronic Obstructive Pulmonary Disease: A Propensity-Matched Cohort Study. AB - Treatment of periodontal diseases has been associated with benefit outcomes for patients with chronic obstructive pulmonary disease (COPD). However, no population-based cohort study has been conducted. We evaluated this relationship by retrospective cohort study using a large population data.Using the National Health Insurance claims data of Taiwan, we identified 5562 COPD patients with periodontal diseases who had received periodontal treatment as the treatment group. The comparison group was selected at a 1:1 ratio matched by the propensity score estimated with age, sex, date of COPD diagnosis and periodontal treatment, and comorbidities. Both groups were followed up for 5 years to compare risks of acute exacerbation, pneumonia, and acute respiratory failure.The incidence rates of adverse respiratory events were significantly lower in the treatment group than in the comparison group: 3.79 versus 4.21 per 100 person-years for emergency room visits, 2.75 versus 3.65 per 100 person-years for hospitalizations, and 0.66 versus 0.75 per 100 person-years for intensive care unit admissions. The treatment group also had a 37% reduced risk of deaths (1.81 vs 2.87 per 100 person-years), with an adjusted hazard ratio of 0.57 (95% confidence interval 0.52-0.62).Periodontal treatment for COPD patients could reduce the risk of adverse respiratory events and mortality. The adequate periodontal health care is important for COPD patients with periodontal diseases. PMID- 27196498 TI - Severity of Diabetes Mellitus and Total Hip or Knee Replacement: A Population Based Case-Control Study. AB - It is generally thought that people with diabetes mellitus (DM) are more likely to suffer from osteoarthritis (OA) due to an increased body mass index (BMI), resulting in mechanical destruction of cartilage. However, previous studies have suggested a coexisting metabolic causality.To evaluate the risk of hip or knee replacement, as a proxy for severe OA, in patients with DM. We additionally evaluated the risk of total joint replacement (TJR) with various proxies for increased DM severity.A population-based case-control study was performed, using the Clinical Practice Research Datalink (CPRD). Cases (n = 94,609) were defined as patients >18 years who had undergone TJR between 2000 and 2012. Controls were matched by age, gender, and general practice. Conditional logistic regression was used to estimate the risk of total knee (TKR) and total hip replacement (THR) surgery associated with use of antidiabetic drugs (ADs). We additionally stratified current AD users by proxies for DM severity.Current AD use was significantly associated with a lower risk of TKR (OR = 0.86 (95% CI = 0.78 0.94)) and THR (OR = 0.90 (95% CI = 0.82-0.99)) compared to patients not using ADs. Moreover, risk of TKR and THR was decreased with increasing HbA1c.This study does not support the theory that DM patients are more likely to suffer from severe OA as compared to patients without diabetes. Moreover, risk of severe OA necessitating TJR decreases with increasing DM severity. This is possibly due to dissimilarities in methodology, a decrease in eligibility for surgery, or variability of OA phenotypes. PMID- 27196499 TI - Atrial Fibrillation on Intensive Care Unit Admission Independently Increases the Risk of Weaning Failure in Nonheart Failure Mechanically Ventilated Patients in a Medical Intensive Care Unit: A Retrospective Case-Control Study. AB - Atrial fibrillation (AF) is one of the most frequent arrhythmias in clinical practice. Previous studies have reported the influence of AF on patients with heart failure (HF). The effect of AF on the non-HF critically ill patients in a medical intensive care unit (ICU) remains largely unclear. The study aimed to investigate the impact of AF presenting on ICU admission on the weaning outcome of non-HF mechanically ventilated patients in a medical ICU.A retrospective observational case-control study was conducted over a 1-year period in a medical ICU at Taipei Veterans General Hospital, a tertiary medical center in north Taiwan. Non-HF mechanically ventilated patients who were successful in their spontaneous breathing trial and underwent ventilator discontinuation were enrolled. The primary outcome measure was the ventilator status after the first episode of ventilator discontinuation.A total of 285 non-HF patients enrolled were divided into AF (n = 62) and non-AF (n = 223) groups. Compared with the non AF patients, the AF patients were significantly associated with old age (P = 0.002), a higher rate of acute respiratory distress syndrome causing respiratory failure (P = 0.015), a higher percentage of sepsis before liberation from mechanical ventilation (MV) (P = 0.004), and a higher serum level of blood urea nitrogen on the day of liberation from MV (P = 0.003). Multivariate logistic regression analysis demonstrated that AF independently increased the risk of weaning failure [adjusted odds ratio (AOR), 3.268; 95% confidence interval (CI), 1.254-8.517; P = 0.015]. Furthermore, the AF patients were found to be independently associated with a high rate of ventilator dependence (log rank test, P = 0.026), prolonged total ventilator use (AOR, 1.979; 95% CI, 1.032 3.794; P = 0.040), increased length of ICU stay (AOR, 2.256; 95% CI, 1.049-4.849; P = 0.037), increased length of hospital stay (AOR, 2.921; 95% CI, 1.363-6.260; P = 0.006), and increased ICU mortality (AOR, 4.143; 95% CI, 1.381-12.424; P = 0.011).AF on ICU admission is an independent risk factor for weaning failure and significantly associated with poor hospital outcome in non-HF mechanically ventilated patients in a medical ICU. PMID- 27196500 TI - PET-CT for Evaluation of Spleen and Liver 18F-FDG Diffuse Uptake Without Lymph Node Enlargement in Lymphoma. AB - The aim of the study was to compare differences between lymphoma and inflammation as indicated by high diffuse uptake of F-fluorodeoxyglucose (F-FDG) in the spleen, liver, and bone marrow without increased F-FDG uptake in the lymph nodes and without enlarged peripheral lymph nodes.Eighteen lymphoma patients and 14 inflammation patients were examined with F-FDG positron emission tomography computer tomography (PET-CT). All patients displayed high diffuse uptake of F-FDG in the spleen, liver, and bone marrow without increased F-FDG uptake in the lymph nodes and without enlarged peripheral lymph nodes. Our analyses compared the maximum standardized uptake values (SUVmax) of F-FDG uptake ratios between the spleen/liver, the spleen/bone marrow, and the liver/bone marrow and further compared spleen sizes between lymphoma and inflammation patients.Using Student t test, no significant differences were found in the SUVmax ratios of spleen/liver and liver/bone marrow between the lymphoma and inflammation patients (t = 0.853, P = 0.401 > 0.05; t = 1.622, P = 0.115 > 0.05). However, the SUVmax ratio of the spleen/bone marrow of the lymphoma patients was significantly different from that of the inflammation patients (t = 2.426, P = 0.021 < 0.05). The spleen size between the lymphoma and inflammation patients was also significantly different (t = 2.911, P = 0.007 < 0.05).As indicated by F-FDG PET-CT, our study demonstrated that lymphoma and inflammation patients displayed a few differences despite both having high diffuse uptake of F-FDG in the spleen, liver, and bone marrow without enlarged peripheral lymph nodes and without increased F-FDG uptake in lymph nodes. PMID- 27196501 TI - Combination Therapy of Radiofrequency Ablation and Transarterial Chemoembolization for Unresectable Hepatocellular Carcinoma: A Retrospective Study. AB - The treatment efficacy of unresectable hepatocellular carcinoma (HCC) is still not promising. This study aimed to compare the efficacy and safety of radiofrequency ablation (RFA) combined with transarterial chemoembolization (TACE) for unresectable HCC with a single treatment.Between June 2009 and June 2012, 132 patients who were diagnosed with unresectable HCC and accepted nonsurgical treatments in our center were enrolled in this retrospective study. On the basis of treatment modality, they were allocated to 3 groups: 49 patients accepted RFA (RFA group); 43 patients accepted TACE (TACE group); and 40 patients accepted RFA following TACE (combination group). Clinical data including complications, treatment success rate, hospitalization costs, intrahepatic recurrence-free survival, overall survival, and factors influencing survival were retrospectively analyzed.Patient characteristics between these groups showed no significant difference. Treatment success was achieved in all patients of 3 groups. The combination group had a significantly higher total hospitalization cost to treatment than the TACE group (63,708.14 +/- 9193.81 Chinese yuan vs 37,534.88 +/- 6802.84 Chinese yuan; P = 0.0000). All complications were controllable and no permanent adverse sequelae or procedure-related deaths were observed. The 3-year intrahepatic recurrence-free survival probability was significantly better in the combination group than in the TACE group (42.50% vs 20.93%; hazard ratio [HR], 0.5105; 95% confidence interval [CI], 0.3022-0.8625; P = 0.0094) or the RFA group (42.50% vs 22.45%; HR, 0.5233; 95% CI, 0.3149-0.8697; P = 0.0111).The 3-year overall survival probability was significantly better in the combination group than in the TACE group (45.00% vs 26.53%; HR, 0.5069; 95% CI, 0.2936-0.8752; P = 0.0100) or the RFA group (45.00% vs 27.91%; HR, 0.4913; 95% CI, 0.2928-0.8246; P = 0.0054). Main tumor size, number of tumors, and treatment modality were demonstrated to be important factors associated with 3 year intrahepatic recurrence-free survival probability and overall survival probability (P < 0.05) by univariate and multivariate analyses.Combination therapy of RFA and TACE was superior to TACE alone or RFA alone in improving survival for patients with unresectable HCC. PMID- 27196502 TI - Lycium barbarum polysaccharide attenuates the cytotoxicity of mutant huntingtin and increases the activity of AKT. AB - Huntington's disease (HD) is an inherited neurodegenerative disease that is caused by the abnormal expansion of CAG repeats in the gene encoding huntingtin (Htt). Reduced AKT phosphorylation and inhibited AKT activity have been shown to be involved in mutant Htt (mHtt)-induced cell death. Lycium barbarum polysaccharide (LBP), the main bioactive component of Lycium barbarum, reportedly has neuroprotective roles in neural injuries, including neurodegenerative diseases. Here, we report that treatment with LBP can increased the viability of HEK293 cells that stably expressed mHtt containing 160 glutamine repeats and significantly improved motor behavior and life span in HD-transgenic mice. Furthermore, we found that in LBP-treated HEK293 cells expressing mHtt, mHtt levels were reduced and the phosphorylation of AKT at Ser473 (p-AKT-Ser473) was significantly increased. We also found that treatment with LBP increased p-AKT Ser473 and decreased mHtt in the cortex, hippocampus and striatum in HD transgenic mice. The level of phosphorylation of p-GSK3beta-Ser9 remained unchanged in both cultured cells and HD-transgenic mice. Our findings suggest that LBP alleviates the cytotoxicity of mHtt by activating AKT and reducing mHtt levels, indicating that LBP may be potentially useful for treating HD. PMID- 27196503 TI - Tertiary sewage treatment by a full-scale compact vertical flow constructed wetland. AB - A 208 m2 compact vertical flow treatment wetland (cVFTW) was studied, treating the rotating biological contactor (RBC) effluent of a busy UK visitor attraction, with widely varying daily sewage loads up to 111 resident population equivalent. Results are presented from monthly spot-sampling and analysis for inlet and outlet concentrations of BOD, SS, NH4-N and TN, including load rates, for the first four-and-a-half years of operation. From commissioning to 13 weeks, outlet BOD, SS and NH4-N were below 12 mg l-1, until a sudden outlet NH4-N spike, to 31.9 mg l-1, the reasons for which are discussed. Thereafter, final effluent quality was <3:<3:<0.5 mg l-1 BOD/SS/NH4-N almost without exception, regardless of the determinand load rates imposed. Recirculation of controlled proportions of cVFTW effluent to the RBC inlet eliminated foul odour emanating from the RBC, and considerably increased overall nitrogen removal via denitrification. Phragmites australis development was poor, with the majority of plants experiencing chlorosis, putatively owing to insufficient bioavailable iron. By year three, despite ongoing weed removal to select for Phragmites, the wetland was increasingly colonised by other species, predominantly Epilobium hirsutum. Glyceria maxima, planted in year three, outcompeted even Epilobium, recommending itself as an alternative to Phragmites in high redox potential treatment wetlands. PMID- 27196504 TI - More apheresis medicine abstracts should be published into manuscripts for clinical use. PMID- 27196505 TI - The bright side of microbial dark matter: lessons learned from the uncultivated majority. AB - Microorganisms are the most diverse and abundant life forms on Earth. Yet, in many environments, only 0.1-1% of them have been cultivated greatly hindering our understanding of the microbial world. However, today cultivation is no longer a requirement for gaining access to information from the uncultivated majority. New genomic information from metagenomics and single cell genomics has provided insights into microbial metabolic cooperation and dependence, generating new avenues for cultivation efforts. Here we summarize recent advances from uncultivated phyla and discuss how this knowledge has influenced our understanding of the topology of the tree of life and metabolic diversity. PMID- 27196508 TI - Bioaccumulation of thallium by the wild plants grown in soils of mining area. AB - Gumuskoy Ag (As, Pb, and Tl) deposits are one of the largest silver deposits in the country and located about 25 km west of Kutahya, Turkey. This study investigated the accumulation and transport of thallium into 11 wild plants in soil of the mining area. Plant samples and their associated soils were collected from the field and Tl contents were measured with inductively coupled plasma mass spectroscopy (ICP-MS). The mean concentrations in the soil, roots, and shoots of the studied plants were, respectively, 170, 318, and 315 mg kg(-1) for Tl. The plants analyzed and collected from the studied area were separated into different groups based on enrichment coefficients of roots and shoots (ECR and ECS). The results showed that because of their higher ECR and ECS, the following could be good bioaccumulators: CY, IS, SL, and VR for Tl. Therefore, these plants can be useful for remediation or phytoremediation of soils polluted by Tl. PMID- 27196506 TI - Probing the Reactivity of the Ce?O Multiple Bond in a Cerium(IV) Oxo Complex. AB - The reactivity of the cerium(IV) oxo complex [(LOEt)2CeIV(?O)(H2O)].MeC(O)NH2 (1; LOEt- = [CoCp{P(O)(OEt)2}3]-, where Cp = eta5-C5H5) toward electrophiles and Bronsted acids has been investigated. The treatment of 1 with acetic anhydride afforded the diacetate complex [CeIV(LOEt)2(O2CMe)2] (2). The reaction of 1 with B(C6F5)3 yielded [CeIV(LOEt)2(Me2CONH2)2][B(C6F5)3(OH)]2 (3), in which the [B(C6F5)3(OH)]- anions are H-bonded to the O-bound acetamide ligands. The treatment of 1 with HCl and HNO3 afforded [CeIV(LOEt)2Cl2] and [CeIV(LOEt)2(NO3)2], respectively. Protonation of 1 with triflic acid (HOTf) gave the diaqua complex [CeIV(LOEt)2(H2O)2](OTf)2 (4), in which the triflate anions are H-bonded to the two aqua ligands. The treatment of 1 with phenol afforded the phenoxide complex [CeIV(LOEt)2(OPh)2] (5). The oxo-bridged bimetallic complex [(LOEt)2(Me2CONH2)CeIV(O)NaLOEt] (6) with the Ce-Ooxo and Na-Ooxo distances of 1.953(4) and 2.341(4) A, respectively, was obtained from the reaction of 1 with [NaLOEt]. Density functional theory calculations showed that the model complex [(LOMe)2CeIV(Me2CONH2)(O)NaLOMe] (6A; LOMe- = [CoCp{P(O)(OMe)2}3]-) contains a polarized Ce?O multiple bond. The energy for dissociation of the {NaLOMe} fragment from 6A in acetonitrile was calculated to be +33.7 kcal/mol, which is higher than that for dissociation of the H-bonded acetamide from [(LOMe)2CeIV(?O)(H2O)].MeC(O)NH2 (1A) (calculated to be +17.4 kcal/mol). In hexanes containing trace water, complex 1 decomposed readily to a mixture of a tetranuclear cerium(IV) oxo cluster, [CeIV4(LOEt)4(MU4-O)(MU2-O)4(MU2-OH)2] (7), and a cerium(III) complex, [CeIII(LOEt)2(H2O)2][LOEt] [8(LOEt)], whereas the cerium/sodium oxo complex 6 is stable under the same conditions. The crystal structures of 3, 4.H2O, 6, and 8(LOEt) have been determined. PMID- 27196507 TI - Long Postpacing Interval After Entrainment of Tachycardia Including a Slow Conduction Zone Within the Circuit. AB - BACKGROUNDS: Postpacing interval (PPI) measured after entrainment pacing describes the distance between pacing site and reentrant circuit. However, the influential features to PPI remain to be elucidated. METHODS AND RESULTS: This study included 22 cases with slow/fast atrioventricular (AV) nodal reentrant tachycardia (AVNRT), 14 orthodromic AV reciprocating tachycardia (AVRT) using an accessary pathway, 22 typical atrial flutter (AFL), and 18 other macroreentrant atrial tachycardia (atypical AFL). Rapid pacing at a pacing cycle length (PCL) 5% shorter than tachycardia cycle length (TCL) was done from a site on or close to the reentry circuit. Pacing sites included the coronary sinus ostium in AVNRT, earliest atrial activation site in AVRT, and cavotricuspid isthmus in typical AFL. In atypical AFL, tachycardia circuit was determined on the basis of CARTO mapping, and then the pacing site was. TCL was significantly longer in AVNRT and AVRT than in typical AFL and atypical AFL (both P < 0.05). PCL minus TCL value was similar among the 4 groups. PPI minus TCL value (milliseconds) was significantly longer in AVNRT (median, 40 [IQR, 29-60.8]) and AVRT (34 [20-47]) than in typical AFL (0 [0-4]) and atypical AFL (3.5 [0-8]) (both P < 0.05). Furthermore, PPI minus TCL was prolonged with shortening of PCL in AVNRT and AVRT (both P < 0.05), whereas it was unchanged in typical AFL (P = 0.50). CONCLUSION: PPI after concealed entrainment is prolonged compared with TCL when the reentry circuit involves a slow conduction zone with a decremental conduction property such as the AV node. PMID- 27196510 TI - Eosinophils and mast cells: a lineage apart. PMID- 27196509 TI - Biomedical ethics education may benefit from integrating compliance and analysis approaches. PMID- 27196511 TI - ILC2s masquerade as ILC1s to drive chronic disease. PMID- 27196512 TI - Protein glycosylation energizes T cells. PMID- 27196513 TI - Tcf1 and Lef1 pack their own HDAC. PMID- 27196520 TI - Immunometabolism of regulatory T cells. AB - The bidirectional interaction between the immune system and whole-body metabolism has been well recognized for many years. Via effects on adipocytes and hepatocytes, immune cells can modulate whole-body metabolism (in metabolic syndromes such as type 2 diabetes and obesity) and, reciprocally, host nutrition and commensal-microbiota-derived metabolites modulate immunological homeostasis. Studies demonstrating the metabolic similarities of proliferating immune cells and cancer cells have helped give birth to the new field of immunometabolism, which focuses on how the cell-intrinsic metabolic properties of lymphocytes and macrophages can themselves dictate the fate and function of the cells and eventually shape an immune response. We focus on this aspect here, particularly as it relates to regulatory T cells. PMID- 27196523 TI - An FTO Gene Variant Moderates the Association between Parental Restriction and Child BMI. AB - OBJECTIVE: This study aimed to explore whether a common variant in the FTO gene moderates the relationship between parental restriction and child BMI. METHODS: This study reports on baseline data from 178 parent-child (ages 9-10 years) dyads. Parents completed the Child Feeding Questionnaire and reported on socio demographic characteristics. Each child's height, weight and FTO rs9939609 genotype was assessed. Ordinary least squares regression was used to fit the child's BMI-percentile on parental restriction and the child's FTO genotype, adjusted for covariates. A likelihood ratio test was used to compare a model with and without a multiplicative interaction term between restriction and genotype. RESULTS: Most participants (93.3%) were white, non-Hispanic. Twenty-three percent of children were overweight/obese and FTO genotype was associated with weight status. Mean parental restriction was statistically higher among overweight/obese vs. normal weight children: 3.3 (SD 0.8) vs. 2.8 (SD 1.0); t-test p-value = 0.002. Parental restriction was positively associated with child BMI-percentile and BMI-z only among children with two copies of the high-risk FTO allele (p for interaction = 0.02), where each one-point increase in parental restriction was associated with a 14.7 increase in the child's BMI-percentile or a 0.56-point increase in the child's BMI z-score. CONCLUSION: For only the children with two high-risk alleles, parental restriction was positively associated with child BMI percentile. PMID- 27196524 TI - Short-term Clinical Course of Knee Pain in Children and Adolescents: A Feasibility Study Using Electronic Methods of Data Collection. AB - BACKGROUND AND PURPOSE: Musculoskeletal disorders, such as knee pain, are common in children and adolescents, but there is a lack of high quality research that evaluates the clinical course of these conditions. The objective of this study was to evaluate the feasibility of conducting a prospective study of children and adolescents with knee pain using electronic methods of data collection. METHODS: Children and adolescents with knee pain that presented to primary care physiotherapy clinics were enrolled and followed-up on a weekly basis via short messaging service (SMS) until their knee pain had recovered (i.e. two consecutive weeks of no pain). Feasibility was assessed in terms of recruitment, retention and response rates to SMS and an online questionnaire. Baseline and 6-month follow-up measures included pain, disability, physical function, physical activity and health related quality of life. Kaplan-Meier survival analysis was used to estimate the median time to knee pain recovery. RESULTS: Thirty participants (mean age 13.0 +/- 2.2 years, 53% boys) were recruited over 26 months. The overall response rate to weekly SMS follow-up was 71.3% (809 received/1135 sent). One third of participants stopped responding to SMS prior to recovery, and these participants typically had a much lower response rate during the time they remained in the study. At 6-month follow-up, 80% of the cohort completed the final online questionnaire, and 29% of participants still reported current knee pain (>=1/10 VAS). The median time for knee pain recovery was 8 weeks (95%CI: 5, 10). CONCLUSION: Electronic data collection alone seems insufficient to track pain recovery in young people and may need to be supplemented with more traditional data collection methods. Researchers should consider further measures to address slow recruitment rates and high attrition when designing large prospective studies of children and adolescents in the future. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27196525 TI - Preventable Incidence and Mortality of Carcinoma Associated With Lifestyle Factors Among White Adults in the United States. AB - IMPORTANCE: Lifestyle factors are important for cancer development. However, a recent study has been interpreted to suggest that random mutations during stem cell divisions are the major contributor to human cancer. OBJECTIVE: To estimate the proportion of cases and deaths of carcinoma (all cancers except skin, brain, lymphatic, hematologic, and nonfatal prostate malignancies) among whites in the United States that can be potentially prevented by lifestyle modification. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study analyzes cancer and lifestyle data from the Nurses' Health Study, the Health Professionals Follow up Study, and US national cancer statistics to evaluate associations between lifestyle and cancer incidence and mortality. EXPOSURES: A healthy lifestyle pattern was defined as never or past smoking (pack-years <5), no or moderate alcohol drinking (<=1 drink/d for women, <=2 drinks/d for men), BMI of at least 18.5 but lower than 27.5, and weekly aerobic physical activity of at least 75 vigorous-intensity or 150 moderate-intensity minutes. Participants meeting all 4 of these criteria made up the low-risk group; all others, the high-risk group. MAIN OUTCOMES AND MEASURES: We calculated the population-attributable risk (PAR) by comparing incidence and mortality of total and major individual carcinomas between the low- and high-risk groups. We further assessed the PAR at the national scale by comparing the low-risk group with the US population. RESULTS: A total of 89 571 women and 46 339 men from 2 cohorts were included in the study: 16 531 women and 11 731 men had a healthy lifestyle pattern (low-risk group), and the remaining 73 040 women and 34 608 men made up the high-risk group. Within the 2 cohorts, the PARs for incidence and mortality of total carcinoma were 25% and 48% in women, and 33% and 44% in men, respectively. For individual cancers, the respective PARs in women and men were 82% and 78% for lung, 29% and 20% for colon and rectum, 30% and 29% for pancreas, and 36% and 44% for bladder. Similar estimates were obtained for mortality. The PARs were 4% and 12% for breast cancer incidence and mortality, and 21% for fatal prostate cancer. Substantially higher PARs were obtained when the low-risk group was compared with the US population. For example, the PARs in women and men were 41% and 63% for incidence of total carcinoma, and 60% and 59% for colorectal cancer, respectively. CONCLUSIONS AND RELEVANCE: A substantial cancer burden may be prevented through lifestyle modification. Primary prevention should remain a priority for cancer control. PMID- 27196526 TI - Characteristics Associated with Home Health Care Referrals at Hospital Discharge: Results from the 2012 National Inpatient Sample. AB - OBJECTIVE: To assess patient- and hospital-level factors associated with home health care (HHC) referrals following nonelective U.S. patient hospitalizations in 2012. DATA SOURCE: The 2012 National Inpatient Sample (NIS). STUDY DESIGN: Retrospective, cross-sectional multivariable logistic regression modeling to assess patient- and hospital-level variables in patient discharges with versus without HHC referrals. DATA COLLECTION: Analysis included 1,109,905 discharges in patients >=65 years with Medicare. PRINCIPAL FINDINGS: About 29.2 percent of discharges were referred to HHC, which were more likely with older age, female sex, urban location, low income, longer length of stay, higher severity of illness scores, diagnoses of heart failure or sepsis, and hospital location in New England (referent: Pacific). CONCLUSIONS: As health policy changes influence postacute HHC, defining specific diagnoses and regional patterns associated with HHC is a first step to optimize postacute HHC services. PMID- 27196530 TI - An efficient algorithm to identify the optimal one-bit perturbation based on the basin-of-state size of Boolean networks. AB - Boolean networks are widely used to model gene regulatory networks and to design therapeutic intervention strategies to affect the long-term behavior of systems. In this paper, we investigate the less-studied one-bit perturbation, which falls under the category of structural intervention. Previous works focused on finding the optimal one-bit perturbation to maximally alter the steady-state distribution (SSD) of undesirable states through matrix perturbation theory. However, the application of the SSD is limited to Boolean networks with about ten genes. In 2007, Xiao et al. proposed to search the optimal one-bit perturbation by altering the sizes of the basin of attractions (BOAs). However, their algorithm requires close observation of the state-transition diagram. In this paper, we propose an algorithm that efficiently determines the BOA size after a perturbation. Our idea is that, if we construct the basin of states for all states, then the size of the BOA of perturbed networks can be obtained just by updating the paths of the states whose transitions have been affected. Results from both synthetic and real biological networks show that the proposed algorithm performs better than the exhaustive SSD-based algorithm and can be applied to networks with about 25 genes. PMID- 27196527 TI - Advances in the transepithelial transport of nanoparticles. AB - The intestinal epithelium represents a barrier to the delivery of nanoparticles (NPs). It prevents intact NPs from efficiently crossing the mucosa to access the circulation, thus limiting the successful application of NP-based oral drug delivery. Recent advances in nanotechnology have provided promising solutions to this challenge. This review describes the potential intestinal absorption pathways of NPs, including the transenterocytic pathway, paracellular pathway and M-cell-mediated pathway. NP properties that influence transcytosis are summarized; and the biodistribution of NPs after oral absorption is described and the future prospects of novel NPs are explored. PMID- 27196531 TI - Signal enhancement in ligand-receptor interactions using dynamic polymers at quartz crystal microbalance sensors. AB - The signal enhancement properties of QCM sensors based on dynamic, biotinylated poly(acrylic acid) brushes has been studied in interaction studies with an anti biotin Fab fragment. The poly(acrylic acid) sensors showed a dramatic increase in signal response with more than ten times higher signal than the carboxyl terminated self-assembled monolayer surface. PMID- 27196532 TI - Ballooning osteolysis in 71 failed total ankle arthroplasties. AB - Background and purpose - Aseptic loosening is a major cause of failure in total ankle arthroplasty (TAA). In contrast to other total joint replacements, large periarticular cysts (ballooning osteolysis) have frequently been observed in this context. We investigated periprosthetic tissue responses in failed TAA, and performed an element analysis of retrieved tissues in failed TAA. Patients and methods - The study cohort consisted of 71 patients undergoing revision surgery for failed TAA, all with hydroxyapatite-coated implants. In addition, 5 patients undergoing primary TAA served as a control group. Radiologically, patients were classified into those with ballooning osteolysis and those without, according to defined criteria. Histomorphometric, immunohistochemical, and elemental analysis of tissues was performed. Von Kossa staining and digital microscopy was performed on all tissue samples. Results - Patients without ballooning osteolysis showed a generally higher expression of lymphocytes, and CD3+, CD11c+, CD20+, and CD68+ cells in a perivascular distribution, compared to diffuse expression. The odds of having ballooning osteolysis was 300 times higher in patients with calcium content >0.5 mg/g in periprosthetic tissue than in patients with calcium content <=0.5 mg/g (p < 0.001). Interpretation - There have been very few studies investigating the pathomechanisms of failed TAA and the cause-effect nature of ballooning osteolysis in this context. Our data suggest that the hydroxyapatite coating of the implant may be a contributory factor. PMID- 27196533 TI - Immunogenicity of Anti-HLA Antibodies in Pancreas and Islet Transplantation. AB - The aim of the current study was to characterize the anti-HLA antibodies before and after pancreatic islet or pancreas transplantation. We assessed the risk of anti-donor-specific antibody (DSA) sensitization in a single-center, retrospective clinical study at Geneva University Hospital. Data regarding clinical characteristics, graft outcome, HLA mismatch, donor HLA immunogenicity, and anti-HLA antibody characteristics were collected. Between January 2008 and July 2014, 18 patients received islet transplants, and 26 patients received a pancreas transplant. Eleven out of 18 patients (61.1%) in the islet group and 12 out of 26 patients (46.2%) in the pancreas group had anti-HLA antibodies. Six patients (33.3%) developed DSAs against HLA of the islets, and 10 patients (38.4%) developed DSAs against HLA of the pancreas. Most of the DSAs were at a low level. Several parameters such as gender, number of times cells were transplanted, HLA mismatch, eplet mismatch and PIRCHE-II numbers, rejection, and infection were analyzed. Only the number of PIRCHE-II was associated with the development of anti-HLA class II de novo DSAs. Overall, the development of de novo DSAs did not influence graft survival as estimated by insulin independence. Our results indicated that pretransplant DSAs at low levels do not restrict islet or pancreas transplantation [especially islet transplantation (27.8% vs. 15.4.%)]. De novo DSAs do occur at a similar rate in both pancreas and islet transplant recipients (mainly of class II), and the immunogenicity of donor HLA is a parameter that should be taken into consideration. When combined with an immunosuppressive regimen and close follow-up, development of low levels of DSAs was not found to result in reduced graft survival or graft function in the current study. PMID- 27196534 TI - Pneumothorax in a young man with anorexia nervosa. AB - Primary spontaneous pneumothorax (PSP) is defined as a pneumothorax that occurs in the absence of an external cause in an individual without underlying generalized lung disease. A number of factors are important and should be carefully considered in the pathogenesis of PSP. This is the first case report of a PSP in a severely malnourished adolescent male with anorexia nervosa (AN) who was involved in excessive physical activity. Clinicians caring for adolescents with AN and vigorous exercise need to be aware of the risk factors associated with the development of a PSP. (c) 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2016; 49:895-898). PMID- 27196535 TI - Optimizing Effect Sizes With Imaging Enrichment and Outcome Choices for Mild Alzheimer Disease Clinical Trials. AB - Recent clinical trials in mild Alzheimer disease (AD) have enriched for amyloid specific positron emission tomography (PET) imaging and used extended versions of the AD Assessment Scale-Cognitive Subscale (ADAS-Cog) in an effort to increase the sensitivity to detect treatment effects. We used data from mild AD participants in the AD Neuroimaging Initiative to model trial effect sizes for 12 and 24-month trials using 3 versions of the ADAS-Cog and increased standardized uptake value ratio (SUVR) cutoffs for amyloid imaging inclusion criteria. For 12 month trials, extended ADAS-Cog versions improved effect sizes. The ADAS-Cog11 elicited larger effect sizes when enriching for SUVR 1.1 only, whereas the ADAS Cog12 and ADAS-Cog13 were associated with larger effect sizes with higher SUVR thresholds. For 24-month trials, extended ADAS-Cog versions increased effect sizes for trials not enriched for amyloid and trials enriched for SUVR 1.1. Only enriching for higher SUVR thresholds (1.3 and 1.4, not 1.1) increased trial power. We conclude that extended versions of the ADAS-Cog improve mild AD trial effect sizes for both 12- and 24-month long studies, whereas amyloid imaging criteria may be most valuable for 12-month trials. PMID- 27196536 TI - Increased Total Urinary Cortisol (tUC) and Serum Brain-derived Neurotrophic Factor (BDNF) Ratio in Alzheimer Disease (AD)-affected Patients. PMID- 27196539 TI - In situ preparation of cubic Cu2O-RGO nanocomposites for enhanced visible-light degradation of methyl orange. AB - There has been a growing interest in gathering together photocatalysis of semiconductors, like cuprous oxide (Cu2O), and the excellent electron transmittability of graphene to produce a graphene-based semiconductor for photocatalytic degradation. In this paper, a mild one-pot in situ synthesis of cubic cuprous oxide-reduced graphene oxide (Cu2O-RGO) nanocomposites has been proposed for the removal of methyl orange. In contrast to pure cubic Cu2O particles under similar preparation conditions, the cubic Cu2O-RGO nanocomposites demonstrate enhanced visible-light-driven photocatalytic activity for methyl orange dye with a 100% degradation rate in 100 min. The enhanced photocatalytic performance is mainly attributed to the increased charge transportation, effective separation of photoelectrons from vacancies, and the improved contact area. PMID- 27196538 TI - Colonic overexpression of the T-type calcium channel Cav 3.2 in a mouse model of visceral hypersensitivity and in irritable bowel syndrome patients. AB - BACKGROUND: Among the different mechanisms involved in irritable bowel syndrome (IBS) physiopathology, visceral hypersensitivity seems to play a key role. It involves sensitization of the colonic primary afferent fibers, especially through an overexpression of ion channels. The aims of this translational study were to investigate the colonic expression of Cav 3.2 calcium channels and their involvement in an animal model of colonic hypersensitivity, and to assess their expression in the colonic mucosa of symptomatic IBS patients. METHODS: This bench to-bed study combined a preclinical experimental study on mice and a case-control clinical study. Preclinical studies were performed on wild-type and Cav 3.2-KO mice. Colonic sensitivity and Cav 3.2 expression were studied after a low-dose treatment of dextran sodium sulfate (DSS 0.5%). Regarding the clinical study, colonic biopsies were performed in 14 IBS patients and 16 controls during a colonoscopy to analyze the mucosal Cav 3.2 expression. KEY RESULTS: Wild-type, but not Cav 3.2-KO, mice developed visceral hypersensitivity without colonic inflammation, after 0.5% DSS treatment. A significant increase of Cav 3.2 mRNA (p = 0.04) was found in the colon of low-dose DSS-treated wild-type (WT) mice compared to their controls. In human colonic biopsies, the Cav 3.2 mRNA level was significantly higher in the IBS group compared to the control group (p = 0.01). The immunofluorescence staining revealed their protein expression in colonic mucosa, particularly in nerve fibers. CONCLUSIONS & INFERENCES: This translational study supports the involvement of the calcium channels Cav 3.2 in abdominal pain, as observed in IBS patients. It opens new therapeutic perspectives based on molecules specifically blocking these channels. PMID- 27196540 TI - MALDI-TOF MS portrait of emetic and non-emetic Bacillus cereus group members. AB - The number of foodborne intoxications caused by emetic Bacillus cereus isolates has increased significantly. As such, rapid and reliable methods to identify emetic strains appear to be clinically relevant. In this study, intact cell matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used to differentiate emetic and non-emetic bacilli. The phyloproteomic clustering of 34 B. cereus emetic and 88 non-emetic isolates classified as B. cereus, Bacillus thuringiensis, Bacillus weihenstephanensis, and Bacillus mycoides, showed (i) a clear separation of both groups at a similarity level of 43%, and (ii) a high relatedness among the emetic isolates (similarity of 78%). Specifically, 83 mass peak classes were recognized in the spectral window range between m/z 4000 and 12 000 that were tentatively assigned to 41 protein variants based on a bioinformatic approach. Mass variation between the emetic and the non-emetic subsets was recorded for 27 of them, including ten ribosomal subunit proteins, for which inter-strain polymorphism was confirmed by gene sequencing. Additional peaks were assigned to other proteins such as small acid soluble proteins, cold shock proteins and hypothetical proteins, e.g., carbohydrate kinase. Moreover, the results were supported by in silico analysis of the biomarkers in 259 members of B. cereus group, including Bacillus anthracis, based on their whole-genome sequences. In conclusion, the proteomic profiling by MALDI-TOF MS is a promising and rapid method for pre-screening B. cereus to identify medically relevant isolates and for epidemiologic purposes. PMID- 27196541 TI - Aging in the Male Face: Intrinsic and Extrinsic Factors. AB - BACKGROUND: Gender is one of the most significant factors that influence facial anatomy and behavior, both key factors in the aging process. OBJECTIVE: To review male facial anatomy, physiology, and behavior and how it contributes to sexual dimorphism in facial aging. METHODS: A MEDLINE search was performed for publications on gender differences in facial anatomy, aging, cutaneous physiology, and behavior. RESULTS: There are differences in both intrinsic and extrinsic aging factors in men. Men have a thicker epidermis and dermis with more active cutaneous appendages including hair growth. Male skin has a reduced antioxidant capacity and increased ultraviolet-induced immunosuppression. The male face is larger and has a unique square shape with less subcutaneous soft tissue, especially at the medial cheek. Men are also more prone to smoking and exhibiting poor sun-protective behavior. The differences in intrinsic and extrinsic aging factors contribute to poor facial aging in men. Men develop more severe rhytides in a unique pattern, show increased periocular aging changes, and are more prone to hair loss. CONCLUSION: This review provides insight into the factors contributing to accelerated male facial aging. Understanding gender differences in aging will help physicians tailor cosmetic treatments for men and minimize extrinsic aging factors. PMID- 27196543 TI - Flight simulation using a Brain-Computer Interface: A pilot, pilot study. AB - As Brain-Computer Interface (BCI) systems advance for uses such as robotic arm control it is postulated that the control paradigms could apply to other scenarios, such as control of video games, wheelchair movement or even flight. The purpose of this pilot study was to determine whether our BCI system, which involves decoding the signals of two 96-microelectrode arrays implanted into the motor cortex of a subject, could also be used to control an aircraft in a flight simulator environment. The study involved six sessions in which various parameters were modified in order to achieve the best flight control, including plane type, view, control paradigm, gains, and limits. Successful flight was determined qualitatively by evaluating the subject's ability to perform requested maneuvers, maintain flight paths, and avoid control losses such as dives, spins and crashes. By the end of the study, it was found that the subject could successfully control an aircraft. The subject could use both the jet and propeller plane with different views, adopting an intuitive control paradigm. From the subject's perspective, this was one of the most exciting and entertaining experiments she had performed in two years of research. In conclusion, this study provides a proof-of-concept that traditional motor cortex signals combined with a decoding paradigm can be used to control systems besides a robotic arm for which the decoder was developed. Aside from possible functional benefits, it also shows the potential for a new recreational activity for individuals with disabilities who are able to master BCI control. PMID- 27196544 TI - Zika virus and microcephaly: is the correlation causal or coincidental? PMID- 27196542 TI - Regulation of MicroRNAs, and the Correlations of MicroRNAs and Their Targeted Genes by Zinc Oxide Nanoparticles in Ovarian Granulosa Cells. AB - Zinc oxide (ZnO) nanoparticles (NPs) have been applied in numerous industrial products and personal care products like sunscreens and cosmetics. The released ZnO NPs from consumer and household products into the environment might pose potential health issues for animals and humans. In this study the expression of microRNAs and the correlations of microRNAs and their targeted genes in ZnO NPs treated chicken ovarian granulosa cells were investigated. ZnSO4 was used as the sole Zn2+ provider to differentiate the effects of NPs from Zn2+. It was found that ZnO-NP-5 MUg/ml specifically regulated the expression of microRNAs involved in embryonic development although ZnO-NP-5 MUg/ml and ZnSO4-10 MUg/ml treatments produced the same intracellular Zn concentrations and resulted in similar cell growth inhibition. And ZnO-NP-5 MUg/ml also specifically regulated the correlations of microRNAs and their targeted genes. This is the first investigation that intact NPs in ZnO-NP-5 MUg/ml treatment specifically regulated the expression of microRNAs, and the correlations of microRNAs and their targeted genes compared to that by Zn2+. This expands our knowledge for biological effects of ZnO NPs and at the same time it raises the health concerns that ZnO NPs might adversely affect our biological systems, even the reproductive systems through regulation of specific signaling pathways. PMID- 27196545 TI - Zika Virus: a re-emerging pathogen with rapidly evolving public health implications. PMID- 27196546 TI - Clinical relevance of genotypic resistance testing today. PMID- 27196537 TI - The genetics of anxiety-related negative valence system traits. AB - NIMH's Research Domain Criteria (RDoC) domain of negative valence systems (NVS) captures constructs of negative affect such as fear and distress traditionally subsumed under the various internalizing disorders. Through its aims to capture dimensional measures that cut across diagnostic categories and are linked to underlying neurobiological systems, a large number of phenotypic constructs have been proposed as potential research targets. Since "genes" represent a central "unit of analysis" in the RDoC matrix, it is important for studies going forward to apply what is known about the genetics of these phenotypes as well as fill in the gaps of existing knowledge. This article reviews the extant genetic epidemiological data (twin studies, heritability) and molecular genetic association findings for a broad range of putative NVS phenotypic measures. We find that scant genetic epidemiological data is available for experimentally derived measures such as attentional bias, peripheral physiology, or brain-based measures of threat response. The molecular genetic basis of NVS phenotypes is in its infancy, since most studies have focused on a small number of candidate genes selected for putative association to anxiety disorders (ADs). Thus, more research is required to provide a firm understanding of the genetic aspects of anxiety related NVS constructs. (c) 2016 Wiley Periodicals, Inc. PMID- 27196548 TI - Diagnostic accuracy of APRI, FIB-4 and Forns for the detection of liver cirrhosis in HIV/HCV-coinfected patients. AB - We determined the diagnostic accuracy and optimal cut off of three indirect fibrosis biomarkers (APRI, FIB-4, Forns) compared with liver stiffness (LS) for the detection of liver cirrhosis in HIV/HCV-coinfected patients. An observational retrospective study on HIV/HCV-coinfected patients with concomitant LS measurement and APRI, FIB-4 and Forns was performed. The presence of liver cirrhosis was defined as a LS >=13 KPa. The diagnostic accuracy and optimal cut off values, compared with LS categorization (<13 vs >=13 KPa), were determined by receiver operating characteristics (ROC) curves.The study sample included 646 patients. The area-under-the ROC curve (95% confidence interval) for the detection of liver cirrhosis were 0.84 (0.81-0.88), 0.87 (0.84-0.91) and 0.87 (0.84-0.90) for APRI, FIB-4 and Forns, respectively. According to the optimal cut off values for liver cirrhosis (>=0.97 for APRI, >=2.02 for FIB-4 and >=7.8 for Forns), 80%, 80% and 82% of subjects were correctly classified by the three indirect fibrosis biomarkers, respectively. Misclassifications were mostly due to false positive cases.The study suggests that indirect fibrosis biomarkers can help clinicians to exclude liver cirrhosis in the management of HIV/HCV co infected patients, reducing the frequency of more expensive or invasive assessments. PMID- 27196547 TI - Italian guidelines for the use of antiretroviral agents and the diagnostic clinical management of HIV-1 infected persons. Update 2015. PMID- 27196550 TI - Colistin inhibits E. coli O157:H7 Shiga-like toxin release, binds endotoxins and protects Vero cells. AB - The role of antibiotics in the treatment of Shiga-like toxin (Stx)-producing E. coli infection is still controversial. This study investigated the effects of colistin on Vero cell cytotoxicity caused by the enterohemorrhagic EC O157:H7, and the effects of colistin on Stx and endotoxin release by EC O157:H7. Vero cells were incubated with supernatant collected from EC O157:H7 cultured for 18 h without (control) or with various concentrations of colistin. In the absence of colistin, Vero cell viability after 48 h was 29.1+/-6.5%. Under the same conditions, the overnight presence of colistin reduced cytotoxicity to Vero cells (viability: 97+/-3.5 to 56.5+/-14.4% for colistin concentrations >=MIC). Sub-MIC concentrations of colistin also provided partial protection (viability: 38.8+/ 12.5 to 36.6+/-14% for 0.125 and 0.06 mcg/ml colistin, respectively). Endotoxins contributed to the cytotoxic effects on Vero cells since lower but still significant protection was observed when colistin was added directly to the supernatant collected from cultures of untreated EC O157:H7. Colistin reduced Stx release in a concentration-dependent manner, also at sub-MIC concentrations. Coincubation of the supernatant from EC O157:H7 cultures with colistin markedly reduced the endotoxin concentration at all doses investigated. In conclusion, colistin protects Vero cells from EC O157:H7 at supra- and sub-MIC concentrations by inhibiting Stx release and binding endotoxins. Colistin might be a valuable treatment for clinically severe forms of EC O157:H7 infection. PMID- 27196549 TI - Chronic HBV infection in pregnant immigrants: a multicenter study of the Italian Society of Infectious and Tropical Diseases. AB - The aims of the study were to estimate the clinical impact of HBV infection in pregnant immigrants and their family members and to identify a useful approach to managing the healthcare of HBsAg-positive immigrants. Included in this study were 143 HBsAg-positive pregnant immigrants of the 1,970 from countries with intermediate/high HBV endemicity who delivered in 8 Italian hospitals in 2012 2013. In addition, 172 family members of 96 HBsAg-positive pregnant immigrants were tested for serum HBsAg. The median age of the 143 HBsAg-positive pregnant immigrants was 31.0+/-12.1 years and the length of stay in Italy 5.0+/-4.1 years; 56.5% were unaware of their HBsAg positivity. HBV DNA was detected in 74.5% of the pregnant immigrants, i.e., 94.3% from Eastern Europe, 72.2% from East Asia and 58.1% from Sub-Saharan Africa. HBV DNA >=2000 IU/mL was detected in 47.8% of pregnant immigrants, associated with ALT >=1.5 times the upper normal value in 15% of cases. Anti-HDV was detected in 10% of cases. HBsAg was detected in 31.3% of the 172 family members. All HBsAg-positive immigrants received counseling on HBV infection and its prevention, and underwent a complete clinical evaluation. The findings validate the approach used for the healthcare management of the HBsAg-positive immigrant population. PMID- 27196551 TI - Occurrence of bacteria producing broad-spectrum beta-lactamases and qnr genes in hospital and urban wastewater samples. AB - The aims were to investigate the level of antibiotic-resistant bacteria in hospital and urban wastewater and to determine the similarity of isolates obtained from wastewater and hospitalized patients. Wastewater samples were collected in September 2013 and 2014. After identification using MALDI-TOF MS, beta-lactamase production was determined by relevant phenotypic tests. Genes responsible for the production of single beta-lactamase groups and Qnr proteins were established. The epidemiological relationship of the isolates from wastewater and hospitalized patients was determined by PFGE. A total of 51 isolates of enterobacteria were obtained. Overall, 45.1% of them produced broad spectrum beta-lactamases. Genes encoding TEM, SHV, CTX-M, CIT, DHA and EBC types of enzymes and Qnr proteins were detected. No broad-spectrum beta-lactamase production was confirmed in the urban wastewater treatment plant. The most important finding was the detection of two identical isolates of K. pneumoniae in 2013, one from a patient's urinary catheter and the other from a wastewater sample. PMID- 27196553 TI - Antiviral activity of human Vdelta2 T-cells against WNV includes both cytolytic and non-cytolytic mechanisms. AB - West Nile virus (WNV) causes a severe central nervous system infection in humans, primarily in the elderly and immunocompromised subjects. Human gammadelta T-cells play a critical role in the immune response against viruses, and studies of WNV meningoencephalitis in laboratory mice described a role of gammadelta T-cells in the protective immune response. Aim of this study was to analyze the cytolytic and non-cytolytic antiviral activity of human Vdelta2 T-cells against WNV replication. The anti-WNV activity of soluble factor released by zoledronic acid (ZA)-activated Vdelta2 T-cell lines and the cytotoxic capability of Vdelta2 T cell lines against WNV-infected cells were tested in vitro. The activation of Vdelta2 T-cell lines was able to inhibit WNV replication through the release of soluble factors. IFN-gamma is massively released by activated Vdelta2 T-cell lines and is involved in the anti-WNV activity. Moreover, the Vdelta2 T-cell lines can efficiently kill WNV-infected cells possibly through perforin-mediated mechanism. Altogether, our results provide insight into the effector functions of human Vdelta2 T-cells against WNV. The possibility to target these cells by ZA, a commercially available drug used in humans, could potentially offer a new immunotherapeutic strategy for WNV infection. PMID- 27196554 TI - Molecular analysis for bacterial contamination in dental unit water lines. AB - Bacterial contamination in dental unit waterlines (DUWLs) was evaluated by molecular techniques in addition to the conventional culture method. Water samples (n=8) from DUWLs were investigated for heterotrophic bacteria by culture method using R2A agar. The selected bacterial antibiotic-resistance genes and Legionella species-specific 16SrDNA were identified by PCR. The profiles of bacterial contamination in DUWLs were further identified by PCR-DGGE. In this study, no antibiotic-resistant or Legionella genes were detected. Polycyclic aromatic hydrocarbon-degrading bacterium, Novosphingobium sp. was the most prevalent in DUWLs. Conventional PCR and PCR-DGGE were shown to be potentially useful for monitoring of bacterial contamination in DUWLs. PMID- 27196555 TI - Features of uropathogenic Escherichia coli able to invade a prostate cell line. AB - RWPE-1 normal prostate cells were tested as an experimental model for adhesion/invasion assays by genotypically and phenotypically characterized community uropathogenic strains of Escherichia coli (UPEC), a frequent cause of urinary tract infections (UTIs) and significant etiologic agent also in bacterial prostatitis. Adhesive ability and strong biofilm production was significantly associated with the bacterial invasive phenotype. Invasive strains derived mainly from male and pediatric patients. This study suggests that such a cell model could usefully integrate other available methods of urovirulence analysis, to deepen knowledge on the bacterial interaction with host cells. PMID- 27196556 TI - HIV-1 RNA quantification in CRF02_AG HIV-1 infection: too easy to make mistakes. AB - The number of patients newly infected by HIV-1 non-B subtypes and circulating recombinant forms (CRFs) is increasing worldwide, including in the western countries. We report on a primary HIV-1 infection in a Caucasian patient. A routine quantitative assay (Nuclisens EasyQ HIV-1 2.0, BioMerieux SA) showed 6,700 HIV-1 RNA copies/ml. A combined antiretroviral therapy (cART) consistent with low baseline HIV-1 RNA was started. Few days later, the analysis performed with REGA HIV-1 Subtyping Tool - Version 3.0 attributed the HIV-1 sequence to the CRF02_AG recombinant form. Therefore, a second real-time PCR assay was performed, using the Versant HIV-1 RNA 1.0 Assay (kPCR) (Siemens HealthCare Diagnostics) which revealed a HIV-1 RNA of 230,000 copies/ml. Consequently, the ongoing cART was potentiated. This case suggests that the wide genetic variability of HIV-1 subtypes may affect the capability of the commonly used assays to detect and accurately quantify HIV-1 RNA in non-B subtypes and CRFs. In presence of CRFs different commercial HIV-1 RNA tests should be performed to find the most reliable for viral load quantification at the diagnosis, because it influences the choice of cART, and during the follow-up. Indeed, international guidelines for HIV-1 infection management suggest to monitor patient' HIV-RNA with the same assay over the course of treatment. As different commercial tests can be performed in the same laboratory with considerable difficulty, the laboratory should select an assay that is suitable not only for the more prevalent strain, but also for less frequent ones that, nevertheless, can occur. Then, knowing and investigating the spread of non-B strains has essential clinical and laboratory implications. PMID- 27196552 TI - Surgical site infection after caesarean section: space for post-discharge surveillance improvements and reliable comparisons. AB - Surgical site infections (SSI) after caesarean section (CS) represent a substantial health system concern. Surveying SSI has been associated with a reduction in SSI incidence. We report the findings of three (2008, 2011 and 2013) regional active SSI surveillances after CS in community hospital of the Latium region determining the incidence of SSI. Each CS was surveyed for SSI occurrence by trained staff up to 30 post-operative days, and association of SSI with relevant characteristics was assessed using binomial logistic regression. A total of 3,685 CS were included in the study. A complete 30 day post-operation follow up was achieved in over 94% of procedures. Overall 145 SSI were observed (3.9% cumulative incidence) of which 131 (90.3%) were superficial and 14 (9.7%) complex (deep or organ/space) SSI; overall 129 SSI (of which 89.9% superficial) were diagnosed post-discharge. Only higher NNIS score was significantly associated with SSI occurrence in the regression analysis. Our work provides the first regional data on CS-associated SSI incidence, highlighting the need for a post discharge surveillance which should assure 30 days post-operation to not miss data on complex SSI, as well as being less labour intensive. PMID- 27196557 TI - Diagnostic performances of antigen detection compared to conventional and nucleic acid detection of Entamoeba histolytica in a non-endemic setting. AB - This study evaluated the immunochromatographic (IC) assay "TECHLAB((r)) E. HISTOLYTICA QUIK CHEKTM" analysing 36 faecal samples and 7 cultured strains. This assay was compared to the methods performed in our laboratory for the diagnosis of amoebiasis. The IC assay revealed a detection limit of 103 trophozoites/g faeces and no cross-reactivity with other parasites and failed to detect E. histolytica antigen in frozen faeces. In our laboratory located in a non-endemic setting this assay could not replace the methods currently used for the diagnosis of amoebiasis. PMID- 27196558 TI - Madura foot in Europe: diagnosis of an autochthonous case by molecular approach and review of the literature. AB - Madura foot is a chronic granulomatous infection of the soft-tissue of the foot and it is endemic in tropical and subtropical countries. Some cases have also been reported in local people or migrants in temperate countries. The microbiological diagnosis requires prolonged bacterial cultures in aerobic and anaerobic conditions, but the use of the molecular approach could be helpful for an early and rapid diagnosis. We describe an autochthonous case of Actinomadura madurae foot infection in an Italian woman. The diagnosis was achieved 36 months after symptoms onset by PCR detection and sequencing of 16S rDNA directly on biopsy. She started therapy with rifampin, trimethoprim-sulfamethoxazole, and amikacin. After 3 months the pain had disappeared and the swelling subsided. We reviewed the literature on Madura foot due to bacterial causative agents in Europe and observed that the median time from onset to diagnosis is high, possibly due to several factors like the difficulties of the microbiological and radiological diagnosis. Our case report and the review of literature point out that the implementation of a surveillance system, the involvement of an infectious diseases specialist, with experience in tropical diseases, and the availability of a microbiology unit to perform feasible and rapid molecular diagnostic tests could result in an earlier diagnosis and an optimal antibiotic therapy of this rare but difficult-to-treat and, above all, difficult-to-diagnose infection. PMID- 27196559 TI - Fatal acute respiratory distress by Toxoplasma gondii in a toxoplasma seronegative liver transplant recipient. AB - The risk of Toxoplasma gondii infection in solid organ transplant recipients is well known but mainly after heart transplantation. We discuss a case of acute respiratory distress caused by Toxoplasma gondii on Day 32 after liver transplantation. The reported case, which is extremely rare, emphasizes how direct examination and Quantitative Polymerase Chain Reaction (QPCR) in broncholaveolar lavage help to diagnose the infection. Given Trimethoprim/Sulfamethoxazole toxicity, systematic prescription of Toxoplasma gondii chemoprophylaxis is not commonly approved in liver transplantation. PMID- 27196561 TI - Hepatocyte Nuclear Factor-1beta Induces Redifferentiation of Dedifferentiated Tubular Epithelial Cells. AB - Tubular epithelial cells (TECs) can be dedifferentiated by repetitive insults, which activate scar-producing cells generated from interstitial cells such as fibroblasts, leading to the accumulation and deposition of extracellular matrix molecules. The dedifferentiated TECs play a crucial role in the development of renal fibrosis. Therefore, renal fibrosis may be attenuated if dedifferentiated TECs are converted back to their normal state (re-epithelialization). However, the mechanism underlying the re-epithelialization remains to be elucidated. In the present study, TGF-beta1, a profibrotic cytokine, induced dedifferentiation of cultured TECs, and the dedifferentiated TECs were re-epithelialized by the removal of TGF-beta1 stimulation. In the re-epithelialization process, transcription factor hepatocyte nuclear factor 1, beta (HNF-1beta) was identified as a candidate molecule involved in inducing re-epithelialization by means of DNA microarray and biological network analysis. In functional validation studies, the re-epithelialization by TGF-beta1 removal was abolished by HNF-1beta knockdown. Furthermore, the ectopic expression of HNF-1beta in the dedifferentiated TECs induced the re-epithelialization without the inhibition of TGF-beta/Smad signaling, even in the presence of TGF-beta1 stimulation. In mouse renal fibrosis model, unilateral ureteral obstruction model, HNF-1beta expression in the TECs of the kidney was suppressed with fibrosis progression. Furthermore, the HNF-1beta downregulated TECs resulted in dedifferentiation, which was characterized by expression of nestin. In conclusion, HNF-1beta suppression in TECs is a crucial event for the dedifferentiation of TECs, and the upregulation of HNF-1beta in TECs has a potential to restore the dedifferentiated TECs into their normal state, leading to the attenuation of renal fibrosis. PMID- 27196560 TI - Genetic Analysis of PLA2G6 in 22 Indian Families with Infantile Neuroaxonal Dystrophy, Atypical Late-Onset Neuroaxonal Dystrophy and Dystonia Parkinsonism Complex. AB - Mutations in PLA2G6 were identified in patients with a spectrum of neurodegenerative conditions, such as infantile neuroaxonal dystrophy (INAD), atypical late-onset neuroaxonal dystrophy (ANAD) and dystonia parkinsonism complex (DPC). However, there is no report on the genetic analysis of families with members affected with INAD, ANAD and DPC from India. Therefore, the main aim of this study was to perform genetic analysis of 22 Indian families with INAD, ANAD and DPC. DNA sequence analysis of the entire coding region of PLA2G6 identified 13 different mutations, including five novel ones (p.Leu224Pro, p.Asp283Asn, p.Arg329Cys, p.Leu491Phe, and p.Arg649His), in 12/22 (54.55%) families with INAD and ANAD. Interestingly, one patient with INAD was homozygous for two different mutations, p.Leu491Phe and p.Ala516Val, and thus harboured four mutant alleles. With these mutations, the total number of mutations in this gene reaches 129. The absence of mutations in 10/22 (45.45%) families suggests that the mutations could be in deep intronic or promoter regions of this gene or these families could have mutations in a yet to be identified gene. The present study increases the mutation landscape of PLA2G6. The present finding will be useful for genetic diagnosis, carrier detection and genetic counselling to families included in this study and other families with similar disease condition. PMID- 27196563 TI - Low serum vitamin D is associated with higher cortical porosity in elderly men. AB - BACKGROUND: Bone loss at peripheral sites in the elderly is mainly cortical and involves increased cortical porosity. However, an association between bone loss at these sites and 25-hydroxyvitamin D has not been reported. OBJECTIVE: To investigate the association between serum levels of 25-hydroxyvitamin D, bone microstructure and areal bone mineral density (BMD) in elderly men. METHODS: A population-based cohort of 444 elderly men (mean +/- SD age 80.2 +/- 3.5 years) was investigated. Bone microstructure was measured by high-resolution peripheral quantitative computed tomography, areal BMD by dual-energy X-ray absorptiometry and serum 25-hydroxyvitamin D and parathyroid hormone levels by immunoassay. RESULTS: Mean cortical porosity at the distal tibia was 14.7% higher (12.5 +/- 4.3% vs. 10.9 +/- 4.1%, P < 0.05) whilst cortical volumetric BMD, area, trabecular bone volume fraction and femoral neck areal BMD were lower in men in the lowest quartile of vitamin D levels compared to the highest. In men with vitamin D deficiency (<25 nmol L-1 ) or insufficiency [25-49 nmol L-1 , in combination with an elevated serum level of parathyroid hormone (>6.8 pmol L-1 )], cortical porosity was 17.2% higher than in vitamin D-sufficient men (P < 0.01). A linear regression model including age, weight, height, daily calcium intake, physical activity, smoking vitamin D supplementation and parathyroid hormone showed that 25-hydroxyvitamin D independently predicted cortical porosity (standardized beta = -0.110, R2 = 1.1%, P = 0.024), area (beta = 0.123, R2 = 1.4%, P = 0.007) and cortical volumetric BMD (beta = 0.125, R2 = 1.4%, P = 0.007) of the tibia as well as areal BMD of the femoral neck (beta = 0.102, R2 = 0.9%, P = 0.04). CONCLUSION: Serum vitamin D is associated with cortical porosity, area and density, indicating that bone fragility as a result of low vitamin D could be due to changes in cortical bone microstructure and geometry. PMID- 27196562 TI - Anthracycline Drugs on Modified Surface of Quercetin-Loaded Polymer Nanoparticles: A Dual Drug Delivery Model for Cancer Treatment. AB - Polymer nanoparticles are vehicles used for delivery of hydrophobic anti-cancer drugs, like doxorubicin, paclitaxel or chemopreventors like quercetin (Q). The present study deals with the synthesis and characterisation of nano formulations (NFs) from Q loaded PLGA (poly lactic-co-glycolic acid) nano particles (NPs) by surface modification. The surface of Q-loaded (NPs) is modified by coating with biopolymers like bovine serum albumin (BSA) or histones (His). Conventional chemotherapeutic drugs adriamycin (ADR) and mitoxantrone (MTX) are bound to BSA and His respectively before being coated on Q-loaded NPs to nano formulate NF1 and NF2 respectively. The sizes of these NFs are in the range 400-500 nm as ascertained by SEM and DLS measurements. Encapsulation of Q in polymer NPs is confirmed from shifts in FT-IR, TGA and DSC traces of Q-loaded NPs compared to native PLGA and Q. Surface modification in NFs is evidenced by three distinct regions in their TEM images; the core, polymer capsule and the coated surface. Negative zeta potential of Q-loaded NPs shifted to positive potential on surface modification in NF1 and NF2. In vitro release of Q from the NFs lasted up to twenty days with an early burst release. NF2 is better formulation than NF1 as loading of MTX is 85% compared to 23% loading of ADR. Such NFs are expected to overcome multi-drug resistance (MDR) by reaching and treating the target cancerous cells by virtue of size, charge and retention. PMID- 27196564 TI - The Survival of Roma Minority Patients on Chronic Hemodialysis Therapy - A Romanian Multicenter Survey. AB - OBJECTIVE: The Roma minority represents the largest ethnic group in Central and South-East European countries. Data regarding the mortality in Roma hemodialysis subjects are limited. We evaluated the 3 year mortality of ESRD Roma patients treated with hemodialysis (HD). STUDY DESIGN AND SETTING: Our prospective cohort study included 600 ESRD patients on HD therapy recruited from 7 HD centers, from the main geographical regions of Romania. The median age of the patients was 56 (19) years, 332 (55.3%) being males, 51 (8.5%) having Roma ethnicity. RESULTS: Roma ESRD patients initiate dialysis at a younger age, 47.8 years vs. 52.3 years (P = 0.017), present higher serum albumin (P = 0.013) and higher serum phosphate levels (P = 0.021). In the Roma group, the overall 3 year mortality was higher when compared to Caucasians (33.3% vs. 24.8%). The multivariate survival analysis revealed that being of Roma ethnicity is an independent risk factor for mortality (HR = 1.74; 95% CI = 1.04-2.91; P = 0.035). CONCLUSIONS: Roma patients with ESRD initiate HD therapy at a younger age as compared to Caucasians. They have a higher 3 year mortality rate and are dying at a younger age. Roma ethnicity represents an independent risk factor for mortality in our cohort. PMID- 27196565 TI - Identification of a Novel Missense FBN2 Mutation in a Chinese Family with Congenital Contractural Arachnodactyly Using Exome Sequencing. AB - Congenital contractural arachnodactyly (CCA, OMIM 121050), also known as Beals Hecht syndrome, is an autosomal dominant disorder of connective tissue. CCA is characterized by arachnodactyly, dolichostenomelia, pectus deformities, kyphoscoliosis, congenital contractures and a crumpled appearance of the helix of the ear. The aim of this study is to identify the genetic cause of a 4-generation Chinese family of Tujia ethnicity with congenital contractural arachnodactyly by exome sequencing. The clinical features of patients in this family are consistent with CCA. A novel missense mutation, c.3769T>C (p.C1257R), in the fibrillin 2 gene (FBN2) was identified responsible for the genetic cause of our family with CCA. The p.C1257R mutation occurs in the 19th calcium-binding epidermal growth factor-like (cbEGF) domain. The amino acid residue cysteine in this domain is conserved among different species. Our findings suggest that exome sequencing is a powerful tool to discover mutation(s) in CCA. Our results may also provide new insights into the cause and diagnosis of CCA, and may have implications for genetic counseling and clinical management. PMID- 27196566 TI - Integrating Self-Affirmation with Health Risk Messages: Effects on Message Evaluation and Response. AB - This study tested a new method of using self-affirmation theory to increase adaptive responses to health risk messages. Participants' self-concepts were affirmed via text integrated with risk messages (public service announcements/PSAs) rather than by methods used in most previous studies that have limited applicability for campaigns employing mediated messages. Participants were exposed to health risk PSAs either including or not including affirming text to examine relative effects on message evaluation and adaptive responses. The moderating effect of personal relevance of the behavior on responses was also examined. Participants exposed to PSAs with integrated, affirming text (affirmed participants) reported more positive attitudes toward the PSA, greater self-efficacy, and greater intention to reduce risky behavior than participants exposed to messages without affirming text (non-affirmed participants). Compared to non-affirmed participants, affirmed participants also reported weaker perceptions of risk severity and equivalent perceptions of susceptibility. The personal relevance of the behavior did not moderate any effects of self-affirmation. Implications for health campaigns that employ mass mediated messages are discussed. PMID- 27196568 TI - The reduced chance of a live birth in women with IBD receiving assisted reproduction is due to a failure to achieve a clinical pregnancy. PMID- 27196569 TI - Why is one arm stronger than two arms? IgG4 antibodies in IgG4-related autoimmune pancreatitis. PMID- 27196567 TI - A pharmacokinetics and safety phase 1/1b study of oral ixazomib in patients with multiple myeloma and severe renal impairment or end-stage renal disease requiring haemodialysis. AB - Renal impairment (RI) is a major complication of multiple myeloma (MM). This study aimed to characterize the single-dose pharmacokinetics (PK) of the oral proteasome inhibitor, ixazomib, in cancer patients with normal renal function [creatinine clearance (CrCl) >=90 ml/min; n = 20), severe RI (CrCl <30 ml/min; n = 14), or end-stage renal disease requiring haemodialysis (ESRD; n = 7). PK and adverse events (AEs) were assessed after a single 3 mg dose of ixazomib. Ixazomib was highly bound to plasma proteins (~99%) in all renal function groups. Unbound and total systemic exposures of ixazomib were 38% and 39% higher, respectively, in severe RI/ESRD patients versus patients with normal renal function. Total ixazomib concentrations were similar in pre- and post-dialyser samples collected from ESRD patients; therefore, ixazomib can be administered without regard to haemodialysis timing. Except for anaemia, the incidence of the most common AEs was generally similar across groups, but grade 3 and 4 AEs were more frequent in the severe RI/ESRD groups versus the normal group (79%/57% vs. 45%), as were serious AEs (43%/43% vs. 15%). The PK and safety results support a reduced ixazomib dose of 3 mg in patients with severe RI/ESRD. PMID- 27196570 TI - Sex-specific effects of TLR9 promoter variants on spontaneous clearance of HCV infection. AB - OBJECTIVE: As pathogen sensors, Toll-like receptors (TLR) play a role in the first defence line during HCV infection. However, the impact of the DNA sensor TLR9 on the natural course of HCV infection is unknown. To address this, TLR9 promoter polymorphisms (single nucleotide polymorphisms (SNPs)) rs187084 and rs5743836 were investigated for their effect on disease progression. DESIGN: Therefore, the TLR9 SNPs and the interferon lambda 4 (IFNL4) rs12979860 were genotyped in chronically HCV type 1 infected (n=333), in patients who spontaneously cleared the infection (n=161), in the Swiss HCV cohort (n=1057) and the well-characterised German (n=305) and Irish (n=198) 'anti-D' cohorts. Functional analyses were done with promoter reporter constructs of human TLR9 in B cells and assessing TLR9 mRNA levels in whole blood of healthy volunteers. RESULTS: The TLR9 rs187084 C allele was associated with spontaneous virus clearance in women of the study cohort (OR=2.15 (95% CI 1.18 to 3.90) p=0.012), of the Swiss HCV cohort (OR=2.06 (95% CI 1.02 to 4.18) p=0.044) and in both 'anti D' cohorts (German: OR=2.01 (95% CI 1.14 to 3.55) p=0.016; Irish: OR=1.93 (95% CI 1.10 to 3.68) p=0.047). Multivariate analysis in the combined study and Swiss HCV cohorts supported the results (OR=1.99 (95% CI 1.30 to 3.05) p=0.002). Functional analyses revealed higher transcriptional activities for both TLR9 variants and an association of the C allele of rs5743836 with allele-specific TLR9 mRNA regulation by oestrogens in women. CONCLUSIONS: TLR9 promoter SNPs are associated with the natural course of HCV infection and show higher transcriptional activities. Our results imply the DNA sensor TLR9 in natural immunity against the RNA virus, HCV. PMID- 27196571 TI - Opposite roles of cannabinoid receptors 1 and 2 in hepatocarcinogenesis. AB - OBJECTIVE: The endocannabinoid system (ECS) exerts key roles in the development of liver fibrosis and fatty liver, two diseases that promote the development of hepatocellular carcinoma (HCC). Although cannabinoids exert potent antitumour effects in vitro, the contribution of the ECS to carcinogenesis in vivo remains elusive. DESIGN: Expression of key components of the ECS, including endocannanabinoids, endocannabinoid-degrading enzymes and endocannabinoid receptors, was determined in healthy liver and tumours. Diethylnitrosamine induced hepatocarcinogenesis was determined in mice deficient in fatty acid amide hydrolase (FAAH), the main anandamide (AEA)-degrading enzyme, in cannabinoid receptor (CB)1, CB2, or transient receptor potential cation channel subfamily V member 1 (TRPV1)-deficient mice. RESULTS: Murine and human HCCs displayed activation of the ECS with strongly elevated expression of CB1 and CB2 but only moderately altered endocannabinoid levels. Contrary to the antitumour effects of cannabinoids in vitro, we observed increased hepatocarcinogenesis in FAAH deficient mice, a mouse model with increased AEA levels. Accordingly, inactivation of CB1, the main receptor for AEA, in wild-type or FAAH-deficient mice suppressed hepatocarcinogenesis. In contrast, inactivation of CB2 increased hepatocarcinogenesis. CB1 was strongly expressed within HCC lesions and its inactivation suppressed proliferation and liver fibrosis. CB2 was predominantly expressed in macrophages. CB2 inactivation decreased the expression of T-cell recruiting chemokines and inhibited hepatic T-cell recruitment including particular CD4+ T cells, a population with known antitumour effects in HCC. TRPV1 deletion did not alter HCC development. CONCLUSIONS: Similar to their role in fibrogenesis, CB1 and CB2 exert opposite effects on hepatocarcinogenesis and may provide novel therapeutic targets. PMID- 27196572 TI - Hepatocyte MyD88 affects bile acids, gut microbiota and metabolome contributing to regulate glucose and lipid metabolism. AB - OBJECTIVE: To examine the role of hepatocyte myeloid differentiation primary response gene 88 (MyD88) on glucose and lipid metabolism. DESIGN: To study the impact of the innate immune system at the level of the hepatocyte and metabolism, we generated mice harbouring hepatocyte-specific deletion of MyD88. We investigated the impact of the deletion on metabolism by feeding mice with a normal control diet or a high-fat diet for 8 weeks. We evaluated body weight, fat mass gain (using time-domain nuclear magnetic resonance), glucose metabolism and energy homeostasis (using metabolic chambers). We performed microarrays and quantitative PCRs in the liver. In addition, we investigated the gut microbiota composition, bile acid profile and both liver and plasma metabolome. We analysed the expression pattern of genes in the liver of obese humans developing non alcoholic steatohepatitis (NASH). RESULTS: Hepatocyte-specific deletion of MyD88 predisposes to glucose intolerance, inflammation and hepatic insulin resistance independently of body weight and adiposity. These phenotypic differences were partially attributed to differences in gene expression, transcriptional factor activity (ie, peroxisome proliferator activator receptor-alpha, farnesoid X receptor (FXR), liver X receptors and STAT3) and bile acid profiles involved in glucose, lipid metabolism and inflammation. In addition to these alterations, the genetic deletion of MyD88 in hepatocytes changes the gut microbiota composition and their metabolomes, resembling those observed during diet-induced obesity. Finally, obese humans with NASH displayed a decreased expression of different cytochromes P450 involved in bioactive lipid synthesis. CONCLUSIONS: Our study identifies a new link between innate immunity and hepatic synthesis of bile acids and bioactive lipids. This dialogue appears to be involved in the susceptibility to alterations associated with obesity such as type 2 diabetes and NASH, both in mice and humans. PMID- 27196575 TI - Reply to letter to the editor of Gut by Dickson and Cox. PMID- 27196574 TI - The neurokinin-2 receptor antagonist ibodutant improves overall symptoms, abdominal pain and stool pattern in female patients in a phase II study of diarrhoea-predominant IBS. AB - BACKGROUND: Tachykinins have been implicated in the pathophysiology of IBS with diarrhoea (IBS-D). Our aim was to study the efficacy and safety of ibodutant, a selective neurokinin-2 (NK2) receptor antagonist, in patients with IBS-D. METHODS: This multinational double-blind, placebo-controlled study recruited 559 patients with IBS-D according to Rome III criteria. After a 2-week treatment-free run-in, patients were randomised to ibodutant 1 mg, 3 mg, 10 mg or placebo once daily for eight consecutive weeks. Responders were those with a combined response of satisfactory relief (weekly binary question yes/no) of overall IBS symptoms and abdominal pain/discomfort on >=75% weeks (primary end point). Secondary end points included abdominal pain and stool pattern. Data were also analysed according to US Food and Drug Administration (FDA)-approved interim end points (improvement of pain and stool consistency). Safety was assessed by monitoring adverse events and laboratory tests. Prespecified statistical analysis involved the whole group as well as gender subgroups. RESULTS: Demographics and baseline characteristics were comparable for all treatment arms. In the overall population, responsiveness tended to increase with escalating ibodutant doses. In the prespecified analysis by gender, ibodutant 10 mg demonstrated significant superiority over placebo in females (p=0.003), while no significant effect occurred in males. This was confirmed for secondary end points and for the responder analysis according to FDA-approved end points. The tolerability and safety of ibodutant was excellent at all doses. CONCLUSIONS: Ibodutant showed dose-dependent efficacy response in IBS-D, reaching statistical significance at the 10 mg dose in female patients. The safety and tolerability profile of ibodutant was similar to placebo. TRIAL REGISTRATION NUMBER: NCT01303224. PMID- 27196573 TI - Tumour CD274 (PD-L1) expression and T cells in colorectal cancer. AB - OBJECTIVE: Evidence suggests that CD274 (programmed death-ligand 1, B7-H1) immune checkpoint ligand repress antitumour immunity through its interaction with the PDCD1 (programmed cell death 1, PD-1) receptor of T lymphocytes in various tumours. We hypothesised that tumour CD274 expression levels might be inversely associated with T-cell densities in colorectal carcinoma tissue. DESIGN: We evaluated tumour CD274 expression by immunohistochemistry in 823 rectal and colon cancer cases within the Nurses' Health Study and Health Professionals Follow-up Study. We conducted multivariable ordinal logistic regression analyses to examine the association of tumour CD274 expression with CD3+, CD8+, CD45RO (PTPRC)+ or FOXP3+ cell density in tumour tissue, controlling for potential confounders including tumour status of microsatellite instability (MSI), CpG island methylator phenotype, long interspersed nucleotide element-1 methylation level and KRAS, BRAF and PIK3CA mutations. RESULTS: CD274 expression in tumour cells or stromal cells (including immune cells) was detected in 731 (89%) or 44 (5%) cases, respectively. Tumour CD274 expression level correlated inversely with FOXP3+ cell density in colorectal cancer tissue (outcome) (ptrend=0.0002). For a unit increase in outcome quartile categories, multivariable OR in the highest (vs lowest) CD274 expression score was 0.22 (95% CI 0.10 to 0.47). Tumour CD274 expression was inversely associated with MSI-high status (p=0.001). CD274 expression was not significantly associated with CD3+, CD8+ or CD45RO+ cell density, pathological lymphocytic reactions or patient survival prognosis. CONCLUSIONS: Tumour CD274 expression is inversely associated with FOXP3+ cell density in colorectal cancer tissue, suggesting a possible influence of CD274 expressing carcinoma cells on regulatory T cells in the tumour microenvironment. PMID- 27196577 TI - Sequential shear-wave elastography of liver and spleen rules out clinically significant portal hypertension in compensated advanced chronic liver disease. PMID- 27196576 TI - Narrow band imaging optical diagnosis of small colorectal polyps in routine clinical practice: the Detect Inspect Characterise Resect and Discard 2 (DISCARD 2) study. AB - BACKGROUND: Accurate optical characterisation and removal of small adenomas (<10 mm) at colonoscopy would allow hyperplastic polyps to be left in situ and surveillance intervals to be determined without the need for histopathology. Although accurate in specialist practice the performance of narrow band imaging (NBI), colonoscopy in routine clinical practice is poorly understood. METHODS: NBI-assisted optical diagnosis was compared with reference standard histopathological findings in a prospective, blinded study, which recruited adults undergoing routine colonoscopy in six general hospitals in the UK. Participating colonoscopists (N=28) were trained using the NBI International Colorectal Endoscopic (NICE) classification (relating to colour, vessel structure and surface pattern). By comparing the optical and histological findings in patients with only small polyps, test sensitivity was determined at the patient level using two thresholds: presence of adenoma and need for surveillance. Accuracy of identifying adenomatous polyps <10 mm was compared at the polyp level using hierarchical models, allowing determinants of accuracy to be explored. FINDINGS: Of 1688 patients recruited, 722 (42.8%) had polyps <10 mm with 567 (78.5%) having only polyps <10 mm. Test sensitivity (presence of adenoma, N=499 patients) by NBI optical diagnosis was 83.4% (95% CI 79.6% to 86.9%), significantly less than the 95% sensitivity (p<0.001) this study was powered to detect. Test sensitivity (need for surveillance) was 73.0% (95% CI 66.5% to 79.9%). Analysed at the polyp level, test sensitivity (presence of adenoma, N=1620 polyps) was 76.1% (95% CI 72.8% to 79.1%). In fully adjusted analyses, test sensitivity was 99.4% (95% CI 98.2% to 99.8%) if two or more NICE adenoma characteristics were identified. Neither colonoscopist expertise, confidence in diagnosis nor use of high definition colonoscopy independently improved test accuracy. INTERPRETATION: This large multicentre study demonstrates that NBI optical diagnosis cannot currently be recommended for application in routine clinical practice. Further work is required to evaluate whether variation in test accuracy is related to polyp characteristics or colonoscopist training. TRIAL REGISTRATION NUMBER: The study was registered with clinicaltrials.gov (NCT01603927). PMID- 27196579 TI - Cardiac mucosa, Barrett's oesophagus and cancer of the gastro-oesophageal junction: what's in a name? PMID- 27196578 TI - Is human albumin solution really the best resuscitation fluid for patients with advanced cirrhosis? PMID- 27196580 TI - Comparative genomics of Crohn's disease-associated adherent-invasive Escherichia coli. AB - OBJECTIVE: Adherent-invasive Escherichia coli (AIEC) are a leading candidate bacterial trigger for Crohn's disease (CD). The AIEC pathovar is defined by in vitro cell-line assays examining specific bacteria/cell interactions. No molecular marker exists for their identification. Our aim was to identify a molecular property common to the AIEC phenotype. DESIGN: 41 B2 phylogroup E. coli strains were isolated from 36 Australian subjects: 19 patients with IBD and 17 without. Adherence/invasion assays were conducted using the I-407 epithelial cell line and survival/replication assays using the THP-1 macrophage cell line. Cytokine secretion tumour necrosis factor ((TNF)-alpha, interleukin (IL) 6, IL-8 and IL-10) was measured using ELISA. The genomes were assembled and annotated, and cluster analysis performed using CD-HIT. The resulting matrices were analysed to identify genes unique/more frequent in AIEC strains compared with non-AIEC strains. Base composition differences and clustered regularly interspaced palindromic repeat (CRISPR) analyses were conducted. RESULTS: Of all B2 phylogroup strains assessed, 79% could survive and replicate in macrophages. Among them, 11/41 strains (5 CD, 2 UCs, 5 non-IBD) also adhere to and invade epithelial cells, a phenotype assigning them to the AIEC pathovar. The AIEC strains were phylogenetically heterogeneous. We did not identify a gene (or nucleic acid base composition differences) common to all, or the majority of, AIEC. Cytokine secretion and CRISPRs were not associated with the AIEC phenotype. CONCLUSIONS: Comparative genomic analysis of AIEC and non-AIEC strains did not identify a molecular property exclusive to the AIEC phenotype. We recommend a broader approach to the identification of the bacteria-host interactions that are important in the pathogenesis of Crohn's disease. PMID- 27196582 TI - Efficacy of vonoprazan-based second-line Helicobacter pylori eradication therapy in patients for whom vonoprazan-based first-line treatment failed. PMID- 27196581 TI - Hiatus hernia in healthy volunteers is associated with intrasphincteric reflux and cardiac mucosal lengthening without traditional reflux. AB - BACKGROUND AND AIMS: Hiatus hernia (HH) is a key mediator of gastro-oesophageal reflux disease but little is known about its significance in the general population. We studied the structure and function of the gastro-oesophageal junction in healthy volunteers with and without HH. METHODS: We compared 15 volunteers with HH, detected by endoscopy or MRI scan, but without gastro oesophageal reflux disease with 15 controls matched for age, gender and body weight. Jumbo biopsies were taken across the squamocolumnar junction (SCJ). High resolution pH metry (12 sensors) and manometry (36 sensors) were performed upright and supine, before and after a meal. The SCJ was marked with an endoscopically placed clip and visualised fluoroscopically. RESULTS: Cardiac mucosa was longer in volunteers with HH (3.5 vs 2.5 mm, p=0.01). There was no excessive acid reflux 5 cm above the upper border of the lower oesophageal sphincter (LOS) in either group but those with HH had short segment reflux 11 mm above the pH transition point after the meal when supine (pH<4 for 5.5% vs 0.3% of time, p=0.01). The SCJ and pH transition point were proximally displaced within the gastro-oesophageal junction in those with HH versus controls (p<0.05). The pH transition point was proximal to the peak LOS pressure point in HH subjects but distal to it in controls after the meal (p<0.05). When supine, the postprandial pH transition point crossed the SCJ in those with HH (p=0.03). CONCLUSIONS: Healthy volunteers with HH have increased intrasphincteric reflux and lengthening of cardiac mucosa in the absence of traditional transsphincteric reflux. PMID- 27196583 TI - MAPping the Wnt pathway to hepatocellular carcinoma recurrence. PMID- 27196584 TI - Integrative microRNA profiling in alcoholic hepatitis reveals a role for microRNA 182 in liver injury and inflammation. AB - OBJECTIVE: MicroRNAs (miRNAs) are well-known regulators of disease pathogenesis and have great potential as biomarkers and therapeutic targets. We aimed at profiling miRNAs in alcoholic hepatitis (AH) and identifying miRNAs potentially involved in liver injury. DESIGN: MiRNA profiling was performed in liver samples from patients with AH, alcohol liver disease, non-alcoholic steatohepatitis, HCV disease and normal liver tissue. Expression of miRNAs was assessed in liver and serum from patients with AH and animal models. Mimic and decoy miR-182 were used in vitro and in vivo to evaluate miR-182's biological functions. RESULTS: MiRNA expression profile in liver was highly altered in AH and distinctive from alcohol induced cirrhotic livers. Moreover, we identified a set of 18 miRNAs predominantly expressed in AH as compared with other chronic liver conditions. Integrative miRNA-mRNA functional analysis revealed the association of AH-altered miRNAs with nuclear receptors, IGF-1 signalling and cholestasis. Interestingly, miR-182 was the most highly expressed miRNA in AH, which correlated with degree of ductular reaction, disease severity and short-term mortality. MiR-182 mimic induced an upregulation of inflammatory mediators in biliary cells. At experimental level, miR-182 was increased in biliary cells in mice fed with 3,5 diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet but not upregulated by alcohol intake or fibrosis. Inhibition of miR-182 in DDC-fed mice reduced liver damage, bile acid accumulation and inflammatory response. CONCLUSIONS: AH is characterised by a deregulated miRNA profile, including miR-182, which is associated with disease severity and liver injury. These results highlight the potential of miRNAs as therapeutic targets and biomarkers in AH. PMID- 27196586 TI - Treatment scale-up to achieve global HCV incidence and mortality elimination targets: a cost-effectiveness model. AB - AIMS: The WHO's draft HCV elimination targets propose an 80% reduction in incidence and a 65% reduction in HCV-related deaths by 2030. We estimate the treatment scale-up required and cost-effectiveness of reaching these targets among injecting drug use (IDU)-acquired infections using Australian disease estimates. METHODS: A mathematical model of HCV transmission, liver disease progression and treatment among current and former people who inject drugs (PWID). Treatment scale-up and the most efficient allocation to priority groups (PWID or patients with advanced liver disease) were determined; total healthcare and treatment costs, quality-adjusted life years (QALYs) and incremental cost effectiveness ratios (ICERs) compared with inaction were calculated. RESULTS: 5662 (95% CI 5202 to 6901) courses per year (30/1000 IDU-acquired infections) were required, prioritised to patients with advanced liver disease, to reach the mortality target. 4725 (3278-8420) courses per year (59/1000 PWID) were required, prioritised to PWID, to reach the incidence target; this also achieved the mortality target, but to avoid clinically unacceptable HCV-related deaths an additional 5564 (1959-6917) treatments per year (30/1000 IDU-acquired infections) were required for 5 years for patients with advanced liver disease. Achieving both targets in this way cost $A4.6 ($A4.2-$A4.9) billion more than inaction, but gained 184 000 (119 000-417 000) QALYs, giving an ICER of $A25 121 ($A11 062-$A39 036) per QALY gained. CONCLUSIONS: Achieving WHO elimination targets with treatment scale-up is likely to be cost-effective, based on Australian HCV burden and demographics. Reducing incidence should be a priority to achieve both WHO elimination goals in the long-term. PMID- 27196585 TI - Tumour-specific delivery of siRNA-coupled superparamagnetic iron oxide nanoparticles, targeted against PLK1, stops progression of pancreatic cancer. AB - OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies and is projected to be the second leading cause of cancer-related death by 2030. Despite extensive knowledge and insights into biological properties and genetic aberrations of PDAC, therapeutic options remain temporary and ineffective. One plausible explanation for the futile response to therapy is an insufficient and non-specific delivery of anticancer drugs to the tumour site. DESIGN: Superparamagnetic iron oxide nanoparticles (SPIONs) coupled with siRNA directed against the cell cycle-specific serine-threonine-kinase, Polo-like kinase-1 (siPLK1-StAv-SPIONs), could serve a dual purpose for delivery of siPLK1 to the tumour and for non-invasive assessment of efficiency of delivery in vivo by imaging the tumour response. siPLK1-StAv-SPIONs were designed and synthesised as theranostics to function via a membrane translocation peptide with added advantage of driving endosomal escape for mediating transportation to the cytoplasm (myristoylated polyarginine peptides) as well as a tumour-selective peptide (EPPT1) to increase intracellular delivery and tumour specificity, respectively. RESULTS: A syngeneic orthotopic as well as an endogenous cancer model was treated biweekly with siPLK1-StAv-SPIONs and tumour growth was monitored by small animal MRI. In vitro and in vivo experiments using a syngeneic orthotopic PDAC model as well as the endogenous LSL-KrasG12D, LSL-Trp53R172H, Pdx 1-Cre model revealed significant accumulation of siPLK1-StAv-SPIONs in PDAC, resulting in efficient PLK1 silencing. Tumour-specific silencing of PLK1 halted tumour growth, marked by a decrease in tumour cell proliferation and an increase in apoptosis. CONCLUSIONS: Our data suggest siPLK1-StAv-SPIONs with dual specificity residues for tumour targeting and membrane translocation to represent an exciting opportunity for targeted therapy in patients with PDAC. PMID- 27196587 TI - Protease inhibition as new therapeutic strategy for GI diseases. AB - The GI tract is the most exposed organ to proteases, both in physiological and pathophysiological conditions. For digestive purposes, the lumen of the upper GI tract contains large amounts of pancreatic proteases, but studies have also demonstrated increased proteolytic activity into mucosal tissues (both in the upper and lower GI tract), associated with pathological conditions. This review aims at outlining the evidences for dysregulated proteolytic homeostasis in GI diseases and the pathogenic mechanisms of increased proteolytic activity. The therapeutic potential of protease inhibition in GI diseases is discussed, with a particular focus on IBDs, functional GI disorders and colorectal cancer. PMID- 27196589 TI - Barriers against split-dose bowel preparation for colonoscopy. AB - OBJECTIVE: Although split regimen is associated with higher adenoma detection and is recommended for elective colonoscopy, its adoption remains suboptimal. The identification of patient-related barriers may improve its implementation. Our aim was to assess patients' attitude towards split regimen and patient-related factors associated with its uptake. DESIGN: In a multicentre, prospective study, outpatients undergoing colonoscopy from 8:00 to 14:00 were given written instructions for 4 L polyethylene glycol bowel preparation, offering the choice between split-dose and day-before regimens and emphasising the superiority of split regimen on colonoscopy outcomes. Uptake of split regimen and association with patient-related factors were explored by a 20-item questionnaire. RESULTS: Of the 1447 patients (mean age 59.2+/-13.5 years, men 54.3%), 61.7% and 38.3% chose a split-dose and day-before regimens, respectively. A linear correlation was observed between time of colonoscopy appointments and split-dose uptake, from 27.3% in 8:00 patients to 96% in 14:00 patients (p<0.001, chi2 for linear trend). At multivariate analysis, colonoscopy appointment before 10:00 (OR 0.14, 95% CI 0.11 to 0.18), travel time to endoscopy service >1 h (OR 0.55, 95% CI 0.38 to 0.79), low education level (OR 0.72, 95% CI 0.54 to 0.96) and female gender (OR 0.74, 95% CI 0.58 to 0.95) were inversely correlated with the uptake of split dose. Overall, the risk of travel interruption and faecal incontinence was slightly increased in split regimen patients (3.0% vs 1.4% and 1.5% vs 0.9%, respectively; p=NS). Split regimen was an independent predictor of adequate colon cleansing (OR 3.34, 95% CI 2.40 to 4.63) and polyp detection (OR 1.46, 95% CI 1.11 to 1.92). CONCLUSION: Patient attitude towards split regimen is suboptimal, especially for early morning examinations. Interventions to improve patient compliance (ie, policies to reorganise colonoscopy timetable, educational initiatives for patient and healthcare providers) should be considered. TRIAL REGISTRATION NUMBER: NCT02287051; pre-result. PMID- 27196588 TI - Comparing CT colonography and flexible sigmoidoscopy: a randomised trial within a population-based screening programme. AB - IMPORTANCE AND AIMS: The role of CT colonography (CTC) as a colorectal cancer (CRC) screening test is uncertain. The aim of our trial was to compare participation and detection rate (DR) with sigmoidoscopy (flexible sigmoidoscopy (FS)) and CTC in a screening setting. DESIGN SETTING AND PARTICIPANTS: We conducted two randomised clinical trials (RCTs). (1) Participation RCT: individuals, aged 58 years, living in Turin (Italy), were randomly assigned to be invited to FS or CTC screening; (2) detection RCT: residents in northern Italy, aged 58-60, giving their consent to recruitment, were randomly allocated to CTC or FS. Polyps >=6 mm at CTC, or 'high-risk' distal lesions at FS, were referred for colonoscopy (TC). MAIN OUTCOME MEASURES: Participation rate (proportion of invitees examined); DR of advanced adenomas or CRC (advanced neoplasia (AN)). RESULTS: Participation was 30.4% (298/980) for CTC and 27.4% (267/976) for FS (relative risk (RR) 1.1; 95% CI 0.98 to 1.29). Among men, participation was higher with CTC than with FS (34.1% vs 26.5%, p=0.011). In the detection RCT, 2673 subjects had FS and 2595 had CTC: the AN DR was 4.8% (127/2673, including 9 CRCs) with FS and 5.1% (133/2595, including 10 CRCs) with CTC (RR 1.08; 95% CI 0.85 to 1.37). Distal AN DR was 3.9% (109/2673) with FS and 2.9% (76/2595) with CTC (RR 0.72; 95% CI 0.54 to 0.96); proximal AN DR was 1.2% (34/2595) for FS vs 2.7% (69/2595) for CTC (RR 2.06; 95% CI 1.37 to 3.10). CONCLUSIONS AND RELEVANCE: Participation and DR for FS and CTC were comparable. AN DR was twice as high in the proximal colon and lower in the distal colon with CTC than with FS. Men were more likely to participate in CTC screening. TRIAL REGISTRATION NUMBER: NCT01739608; Pre-results. PMID- 27196590 TI - The gut-adherent microbiota of PSC-IBD is distinct to that of IBD. PMID- 27196591 TI - Reduced risk of UC in families affected by appendicitis: a Danish national cohort study. AB - OBJECTIVE: The possible aetiological link between appendicitis and UC remains unclear. In order to investigate the hereditary component of the association, we studied the risk of UC in family members of individuals with appendicitis. DESIGN: A cohort of 7.1 million individuals was established by linkage of national registers in Denmark with data on kinship and diagnoses of appendicitis and UC. Poisson regression models were used to calculate first hospital contact rate ratios (RR) for UC with 95% CIs between individuals with or without relatives with a history of appendicitis. RESULTS: During 174 million person years of follow-up between 1977 and 2011, a total of 190 004 cohort members developed appendicitis and 45 202 developed UC. Individuals having a first-degree relative with appendicitis before age 20 years had significantly reduced risk of UC (RR 0.90; 95% CI 0.86 to 0.95); this association was stronger in individuals with a family predisposition to UC (RR 0.66; 95% CI 0.51 to 0.83). CONCLUSIONS: Individuals with a first-degree relative diagnosed with appendicitis before age 20 years are at reduced risk of UC, particularly when there is a family predisposition to UC. Our findings question a previously hypothesised direct protective influence of appendicitis on inflammation of the large bowel. Rather, genetic or environmental factors linked to an increased risk of appendicitis while being protective against UC may explain the repeatedly reported reduced relative risk of UC in individuals with a history of appendicitis. PMID- 27196592 TI - Stool frequency is associated with gut microbiota composition. PMID- 27196593 TI - Author response to letter: colonic stenting in patients on P2Y12 receptor antagonists and direct oral anticoagulants-are current BSG/ESGE guidelines practical? PMID- 27196594 TI - Appendectomy does not decrease the risk of future colectomy in UC: results from a large cohort and meta-analysis. AB - OBJECTIVES: Early appendectomy is inversely associated with the development of UC. However, the impact of appendectomy on the clinical course of UC is controversial, generally favouring a milder disease course. We aim to describe the effect appendectomy has on the disease course of UC with focus on the timing of appendectomy in relation to UC diagnosis. DESIGN: Using the National Institute of Diabetes and Digestive and Kidney Diseases Inflammatory Bowel Disease Genetics Consortium database of patients with UC, the risk of colectomy was compared between patients who did and did not undergo appendectomy. In addition, we performed a meta-analysis of studies that examined the association between appendectomy and colectomy. RESULTS: 2980 patients with UC were initially included. 111 (4.4%) patients with UC had an appendectomy; of which 63 were performed prior to UC diagnosis and 48 after diagnosis. In multivariable analysis, appendectomy performed at any time was an independent risk factor for colectomy (OR 1.9, 95% CI 1.1 to 3.1), with appendectomy performed after UC diagnosis most strongly associated with colectomy (OR 2.2, 95% CI 1.1 to 4.5). An updated meta-analysis showed appendectomy performed either prior to or after UC diagnosis had no effect on colectomy rates. CONCLUSIONS: Appendectomy performed at any time in relation to UC diagnosis was not associated with a decrease in severity of disease. In fact, appendectomy after UC diagnosis may be associated with a higher risk of colectomy. These findings question the proposed use of appendectomy as treatment for UC. PMID- 27196595 TI - Lymphotoxin beta receptor signalling executes Helicobacter pylori-driven gastric inflammation in a T4SS-dependent manner. AB - OBJECTIVE: Lymphotoxin beta receptor (LTbetaR) signalling has been implicated in inflammation-associated tumour development in different tissues. We have analysed the role of LTbetaR and alternative NF-kappaB signalling in Helicobacter pylori mediated gastric inflammation and pathology. DESIGN: We analysed several ligands and receptors of the alternative NF-kappaB pathway, RelB, p52 nuclear translocation and target genes in tissue samples of H. pylori-infected patients with different degrees of gastritis or early gastric tumours by in situ hybridisation, immunohistochemistry, Western blot and real-time PCR analyses. Molecular mechanisms involved in LTbetaR activation by H. pylori were assessed in vitro using human gastric cancer cell lines and distinct H. pylori isolates. The effects of blocking or agonistically activating LTbetaR on gastric pathology during challenge with a human pathogenic H. pylori strain were studied in a mouse model. RESULTS: Among the tested candidates, LT was significantly increased and activated alternative NF-kappaB signalling was observed in the gastric mucosa of H. pylori-infected patients. H. pyloriinduced LTbetaR-ligand expression in a type IV secretion system-dependent but CagA-independent manner, resulting in activation of the alternative NF-kappaB pathway, which was further enhanced by blocking canonical NF-kappaB during infection. Blocking LTbetaR signalling in vivo suppressed H. pylori-driven gastritis, whereas LTbetaR activation in gastric epithelial cells of infected mice induced a broadened pro-inflammatory chemokine milieu, resulting in exacerbated pathology. CONCLUSIONS: LTbetaR-triggered activation of alternative NF-kappaB signalling in gastric epithelial cells executes H. pylori-induced chronic gastritis, representing a novel target to restrict gastric inflammation and pathology elicited by H. pylori, while exclusively targeting canonical NF-kappaB may aggravate pathology by enhancing the alternative pathway. PMID- 27196597 TI - Experimental infection of rabbits with genotype 3 hepatitis E virus produced both chronicity and kidney injury. PMID- 27196598 TI - Drug development in IBD: from novel target identification to early clinical trials. PMID- 27196600 TI - Preclinical disease and preventive strategies in IBD: perspectives, challenges and opportunities. PMID- 27196601 TI - Reply to the letter by Dr Graham concerning ethical and interpretation issues with vonoprazan-containing H. pylori eradication therapy. PMID- 27196596 TI - Transition from childhood to adulthood in coeliac disease: the Prague consensus report. AB - The process of transition from childhood to adulthood is characterised by physical, mental and psychosocial development. Data on the transition and transfer of care in adolescents/young adults with coeliac disease (CD) are scarce. In this paper, 17 physicians from 10 countries (Sweden, Italy, the USA, Germany, Norway, the Netherlands, Australia, Britain, Israel and Denmark) and two representatives from patient organisations (Association of European Coeliac Societies and the US Celiac Disease Foundation) examined the literature on transition from childhood to adulthood in CD. Medline (Ovid) and EMBASE were searched between 1900 and September 2015. Evidence in retrieved reports was evaluated using the Grading of Recommendation Assessment, Development and Evaluation method. The current consensus report aims to help healthcare personnel manage CD in the adolescent and young adult and provide optimal care and transition into adult healthcare for patients with this disease. In adolescence, patients with CD should gradually assume exclusive responsibility for their care, although parental support is still important. Dietary adherence and consequences of non-adherence should be discussed during transition. In most adolescents and young adults, routine small intestinal biopsy is not needed to reconfirm a childhood diagnosis of CD based on European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) or North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) criteria, but a biopsy may be considered where paediatric diagnostic criteria have not been fulfilled, such as, in a patient without biopsy at diagnosis, additional serology (endomysium antibody) has not been performed to confirm 10-fold positivity of tissue transglutaminase antibodies or when a no biopsy strategy has been adopted in an asymptomatic child. PMID- 27196599 TI - Targeting super-enhancer-associated oncogenes in oesophageal squamous cell carcinoma. AB - OBJECTIVES: Oesophageal squamous cell carcinoma (OSCC) is an aggressive malignancy and the major histological subtype of oesophageal cancer. Although recent large-scale genomic analysis has improved the description of the genetic abnormalities of OSCC, few targetable genomic lesions have been identified, and no molecular therapy is available. This study aims to identify druggable candidates in this tumour. DESIGN: High-throughput small-molecule inhibitor screening was performed to identify potent anti-OSCC compounds. Whole transcriptome sequencing (RNA-Seq) and chromatin immunoprecipitation sequencing (ChIP-Seq) were conducted to decipher the mechanisms of action of CDK7 inhibition in OSCC. A variety of in vitro and in vivo cellular assays were performed to determine the effects of candidate genes on OSCC malignant phenotypes. RESULTS: The unbiased high-throughput small-molecule inhibitor screening led us to discover a highly potent anti-OSCC compound, THZ1, a specific CDK7 inhibitor. RNA Seq revealed that low-dose THZ1 treatment caused selective inhibition of a number of oncogenic transcripts. Notably, further characterisation of the genomic features of these THZ1-sensitive transcripts demonstrated that they were frequently associated with super-enhancer (SE). Moreover, SE analysis alone uncovered many OSCC lineage-specific master regulators. Finally, integrative analysis of both THZ1-sensitive and SE-associated transcripts identified a number of novel OSCC oncogenes, including PAK4, RUNX1, DNAJB1, SREBF2 and YAP1, with PAK4 being a potential druggable kinase. CONCLUSIONS: Our integrative approaches led to a catalogue of SE-associated master regulators and oncogenic transcripts, which may significantly promote both the understanding of OSCC biology and the development of more innovative therapies. PMID- 27196603 TI - Elemental Analysis of Bone, Teeth, Horn and Antler in Different Animal Species Using Non-Invasive Handheld X-Ray Fluorescence. AB - Mineralized tissues accumulate elements that play crucial roles in animal health. Although elemental content of bone, blood and teeth of human and some animal species have been characterized, data for many others are lacking, as well as species comparisons. Here we describe the distribution of elements in horn (Bovidae), antler (Cervidae), teeth and bone (humerus) across a number of species determined by handheld X-ray fluorescence (XRF) to better understand differences and potential biological relevance. A difference in elemental profiles between horns and antlers was observed, possibly due to the outer layer of horns being comprised of keratin, whereas antlers are true bone. Species differences in tissue elemental content may be intrinsic, but also related to feeding habits that contribute to mineral accumulation, particularly for toxic heavy metals. One significant finding was a higher level of iron (Fe) in the humerus bone of elephants compared to other species. This may be an adaptation of the hematopoietic system by distributing Fe throughout the bone rather than the marrow, as elephant humerus lacks a marrow cavity. We also conducted discriminant analysis and found XRF was capable of distinguishing samples from different species, with humerus bone being the best source for species discrimination. For example, we found a 79.2% correct prediction and success rate of 80% for classification between human and non-human humerus bone. These findings show that handheld XRF can serve as an effective tool for the biological study of elemental composition in mineralized tissue samples and may have a forensic application. PMID- 27196605 TI - Raspberry Ketone Analogs: Vapour Pressure Measurements and Attractiveness to Queensland Fruit Fly, Bactrocera tryoni (Froggatt) (Diptera: Tephritidae). AB - The Queensland fruit fly, Bactrocera tryoni (Froggatt) (Q-fly), is a major horticultural pest in Eastern Australia. Effective monitoring, male annihilation technique (MAT) and mass trapping (MT) are all important for control and require strong lures to attract flies to traps or toxicants. Lure strength is thought to be related in part to volatility, but little vapour pressure data are available for most Q-fly lures. Raspberry ketone (4-(4-hydroxyphenyl)-2-butanone) and analogs that had esters (acetyl, difluoroacetyl, trifluoroacetyl, formyl, propionyl) and ethers (methyl ether, trimethylsilyl ether) in replacement of the phenolic group, and in one case also had modification of the 2-butanone side chain, were measured for their vapour pressures by differential scanning calorimetry (DSC), and their attractiveness to Q-fly was assessed in small cage environmentally controlled laboratory bioassays. Maximum response of one category of compounds, containing both 2-butanone side chain and ester group was found to be higher than that of the other group of compounds, of which either of 2 butanone or ester functionality was modified. However, linear relationship between vapour pressure and maximum response was not significant. The results of this study indicate that, while volatility may be a factor in lure effectiveness, molecular structure is the dominating factor for the series of molecules investigated. PMID- 27196604 TI - Dimerization and Transactivation Domains as Candidates for Functional Modulation and Diversity of Sox9. AB - Sox9 plays an important role in a large variety of developmental pathways in vertebrates. It is composed of three domains: high-mobility group box (HMG box), dimerization (DIM) and transactivation (TAD). One of the main processes for regulation and variability of the pathways involving Sox9 is the self-gene expression regulation of Sox9. However, the subsequent roles of the Sox9 domains can also generate regulatory modulations. Studies have shown that TADs can bind to different types of proteins and its function seems to be influenced by DIM. Therefore, we hypothesized that both domains are directly associated and can be responsible for the functional variability of Sox9. We applied a method based on a broad phylogenetic context, using sequences of the HMG box domain, to ensure the homology of all the Sox9 copies used herein. The data obtained included 4,921 sequences relative to 657 metazoan species. Based on coevolutionary and selective pressure analyses of the Sox9 sequences, we observed coevolutions involving DIM and TADs. These data, along with the experimental data from literature, indicate a functional relationship between these domains. Moreover, DIM and TADs may be responsible for the functional plasticity of Sox9 because they are more tolerant for molecular changes (higher Ka/Ks ratio than the HMG box domain). This tolerance could allow a differential regulation of target genes or promote novel targets during transcriptional activation. In conclusion, we suggest that DIM and TADs functional association may regulate differentially the target genes or even promote novel targets during transcription activation mediated by Sox9 paralogs, contributing to the subfunctionalization of Sox9a and Sox9b in teleosts. PMID- 27196607 TI - Correction: Structure of Type IIL Restriction-Modification Enzyme MmeI in Complex with DNA Has Implications for Engineering New Specificities. AB - [This corrects the article DOI: 10.1371/journal.pbio.1002442.]. PMID- 27196606 TI - Codon Adaptation of Plastid Genes. AB - Codon adaptation is codon usage bias that results from selective pressure to increase the translation efficiency of a gene. Codon adaptation has been studied across a wide range of genomes and some early analyses of plastids have shown evidence for codon adaptation in a limited set of highly expressed plastid genes. Here we study codon usage bias across all fully sequenced plastid genomes which includes representatives of the Rhodophyta, Alveolata, Cryptophyta, Euglenozoa, Glaucocystophyceae, Rhizaria, Stramenopiles and numerous lineages within the Viridiplantae, including Chlorophyta and Embryophyta. We show evidence that codon adaptation occurs in all genomes except for two, Theileria parva and Heicosporidium sp., both of which have highly reduced gene contents and no photosynthesis genes. We also show evidence that selection for codon adaptation increases the representation of the same set of codons, which we refer to as the adaptive codons, across this wide range of taxa, which is probably due to common features descended from the initial endosymbiont. We use various measures to estimate the relative strength of selection in the different lineages and show that it appears to be fairly strong in certain Stramenopiles and Chlorophyta lineages but relatively weak in many members of the Rhodophyta, Euglenozoa and Embryophyta. Given these results we propose that codon adaptation in plastids is widespread and displays the same general features as adaptation in eubacterial genomes. PMID- 27196609 TI - Comprehensive personal RF-EMF exposure map and its potential use in epidemiological studies. AB - In recent years, numerous epidemiological studies, which deal with the potential effects of mobile phone antennas on health, have almost exclusively focused on their distance to mobile phone base stations. Although it is known that this is not the best approach to the problem, this situation occurs due to the numerous difficulties when determining the personal exposure to the radiofrequency electromagnetic fields (RF-EMF). However, due to the rise of personal exposimeters, the evolution of spatial statistics, the development of geographical information systems and the use of powerful software, new alternatives are available to deal with these epidemiological studies and thus overcome the aforementioned difficulties. Using these tools, this paper presents a lattice map of personal RF-EMF exposure from exterior mobile phone base stations, covering the entire 110 administrative regions in the city of Albacete (Spain). For this purpose, we used a personal exposimeter, Satimo EME Spy 140 model, performing measurements every 4s The exposimeter was located inside the plastic basket of a bicycle, whose versatility permitted the access to all the zones of the city. Once the exposure map was prepared, its relation with the known antenna locations was studied. The 64 mobile telephone antennas of the city were also georeferenced; the randomness of both variables (exposure and antennas) were studied by means of the Moran's I test. Results showed that the distribution of the antennas follows a grouped pattern (p<0.001), while the distribution of the average exposure values have a random distribution (p=0.618). In addition, we showed two Spearman correlation studies: the first between the average exposure values and the number of mobile telephone antennas per administrative region, and the second, also considering the antennas of the neighbouring regions. No substantial correlation was detected in either of the two cases. This study also reveals the weaknesses of the epidemiological studies, which only take into account the distance to the antennas, which would provide a new approach to the problem. By precisely knowing the resident population of each administrative region of the city, this proves to be highly useful to rely on a prepared aggregate data map based on the mean exposure values to RF-EMF in these sections. The displayed map would permit the execution of more accurate epidemiological studies, since it would be possible to compare the exposure measurements with the incidence data of a disease. PMID- 27196608 TI - Variable Nitrogen Fixation in Wild Populus. AB - The microbiome of plants is diverse, and like that of animals, is important for overall health and nutrient acquisition. In legumes and actinorhizal plants, a portion of essential nitrogen (N) is obtained through symbiosis with nodule inhabiting, N2-fixing microorganisms. However, a variety of non-nodulating plant species can also thrive in natural, low-N settings. Some of these species may rely on endophytes, microorganisms that live within plants, to fix N2 gas into usable forms. Here we report the first direct evidence of N2 fixation in the early successional wild tree, Populus trichocarpa, a non-leguminous tree, from its native riparian habitat. In order to measure N2 fixation, surface-sterilized cuttings of wild poplar were assayed using both 15N2 incorporation and the commonly used acetylene reduction assay. The 15N label was incorporated at high levels in a subset of cuttings, suggesting a high level of N-fixation. Similarly, acetylene was reduced to ethylene in some samples. The microbiota of the cuttings was highly variable, both in numbers of cultured bacteria and in genetic diversity. Our results indicated that associative N2-fixation occurred within wild poplar and that a non-uniformity in the distribution of endophytic bacteria may explain the variability in N-fixation activity. These results point to the need for molecular studies to decipher the required microbial consortia and conditions for effective endophytic N2-fixation in trees. PMID- 27196619 TI - Binational Dengue Outbreak Along the United States-Mexico Border - Yuma County, Arizona, and Sonora, Mexico, 2014. AB - Dengue is an acute febrile illness caused by any of four dengue virus types (DENV 1-4). DENVs are transmitted by mosquitos of the genus Aedes (1) and are endemic throughout the tropics (2). In 2010, an estimated 390 million DENV infections occurred worldwide (2). During 2007-2013, a total of three to 10 dengue cases were reported annually in Arizona and all were travel-associated. During September-December 2014, coincident with a dengue outbreak in Sonora, Mexico, 93 travel-associated dengue cases were reported in Arizona residents; 70 (75%) cases were among residents of Yuma County, which borders San Luis Rio Colorado, Sonora, Mexico. San Luis Rio Colorado reported its first case of locally acquired dengue in September 2014. To investigate the temporal relationship of the dengue outbreaks in Yuma County and San Luis Rio Colorado and compare patient characteristics and signs and symptoms, passive surveillance data from both locations were analyzed. In addition, household-based cluster investigations were conducted near the residences of reported dengue cases in Yuma County to identify unreported cases and assess risk for local transmission. Surveillance data identified 52 locally acquired cases (21% hospitalized) in San Luis Rio Colorado and 70 travel-associated cases (66% hospitalized) in Yuma County with illness onset during September-December 2014. Among 194 persons who participated in the cluster investigations in Yuma County, 152 (78%) traveled to Mexico at least monthly during the preceding 3 months. Four (2%) of 161 Yuma County residents who provided serum samples for diagnostic testing during cluster investigations had detectable DENV immunoglobulin M (IgM); one reported a recent febrile illness, and all four had traveled to Mexico during the preceding 3 months. Entomologic assessments among 105 households revealed 24 water containers per 100 houses colonized by Ae. aegypti. Frequent travel to Mexico and Ae. aegypti colonization indicate risk for local transmission of DENV in Yuma County. Public health officials in Sonora and Arizona should continue to collaborate on dengue surveillance and educate the public regarding mosquito abatement and avoidance practices. Clinicians evaluating patients from the U.S.-Mexico border region should consider dengue in patients with acute febrile illness and report suspected cases to public health authorities. PMID- 27196620 TI - Prenatal maternal psychosocial stress and risk of asthma and allergy in their offspring: protocol for a systematic review and meta-analysis. PMID- 27196622 TI - New Recommendations for Extent of Thyroidectomy and Active Surveillance for the Treatment of Differentiated Thyroid Cancer. PMID- 27196610 TI - Mitochondrial metabolic remodeling in response to genetic and environmental perturbations. AB - Mitochondria are metabolic hubs within mammalian cells and demonstrate significant metabolic plasticity. In oxygenated environments with ample carbohydrate, amino acid, and lipid sources, they are able to use the tricarboxylic acid cycle for the production of anabolic metabolites and ATP. However, in conditions where oxygen becomes limiting for oxidative phosphorylation, they can rapidly signal to increase cytosolic glycolytic ATP production, while awaiting hypoxia-induced changes in the proteome mediated by the activity of transcription factors such as hypoxia-inducible factor 1. Hypoxia is a well-described phenotype of most cancers, driving many aspects of malignancy. Improving our understanding of how mitochondria change their metabolism in response to this stimulus may therefore elicit the design of new selective therapies. Many of the recent advances in our understanding of mitochondrial metabolic plasticity have been acquired through investigations of cancer-associated mutations in metabolic enzymes, including succinate dehydrogenase, fumarate hydratase, and isocitrate dehydrogenase. This review will describe how metabolic perturbations induced by hypoxia and mutations in these enzymes have informed our knowledge in the control of mitochondrial metabolism, and will examine what this may mean for the biology of the cancers in which these mutations are observed. WIREs Syst Biol Med 2016, 8:272-285. doi: 10.1002/wsbm.1334 For further resources related to this article, please visit the WIREs website. PMID- 27196621 TI - Average Stand Age from Forest Inventory Plots Does Not Describe Historical Fire Regimes in Ponderosa Pine and Mixed-Conifer Forests of Western North America. AB - Quantifying historical fire regimes provides important information for managing contemporary forests. Historical fire frequency and severity can be estimated using several methods; each method has strengths and weaknesses and presents challenges for interpretation and verification. Recent efforts to quantify the timing of historical high-severity fire events in forests of western North America have assumed that the "stand age" variable from the US Forest Service Forest Inventory and Analysis (FIA) program reflects the timing of historical high-severity (i.e. stand-replacing) fire in ponderosa pine and mixed-conifer forests. To test this assumption, we re-analyze the dataset used in a previous analysis, and compare information from fire history records with information from co-located FIA plots. We demonstrate that 1) the FIA stand age variable does not reflect the large range of individual tree ages in the FIA plots: older trees comprised more than 10% of pre-stand age basal area in 58% of plots analyzed and more than 30% of pre-stand age basal area in 32% of plots, and 2) recruitment events are not necessarily related to high-severity fire occurrence. Because the FIA stand age variable is estimated from a sample of tree ages within the tree size class containing a plurality of canopy trees in the plot, it does not necessarily include the oldest trees, especially in uneven-aged stands. Thus, the FIA stand age variable does not indicate whether the trees in the predominant size class established in response to severe fire, or established during the absence of fire. FIA stand age was not designed to measure the time since a stand replacing disturbance. Quantification of historical "mixed-severity" fire regimes must be explicit about the spatial scale of high-severity fire effects, which is not possible using FIA stand age data. PMID- 27196625 TI - Evaluation and management of pediatric nasal obstruction: A survey of practice patterns. AB - BACKGROUND: Inferior turbinate (IT) hypertrophy and adenoid hypertrophy are both causes of pediatric nasal obstruction. OBJECTIVE: The purpose of this survey was to study nasal obstruction evaluation and management among pediatric otolaryngologists with respect to IT and adenoid hypertrophy. METHODS: A questionnaire with embedded clinical videos was sent electronically to American Society of Pediatric Otolaryngology members. RESULTS: A total of 435 questionnaires were sent, and 75 were completed. Respondents were presented with scenarios that involved a 7-year-old child with nasal obstruction unresponsive to medical therapy, and the respondents were asked to choose a surgical plan, either IT reduction, adenoidectomy, or combined IT reduction and adenoidectomy. Three questions described the extent of IT and adenoid obstruction in text form, although three questions included a video of the child's nasal endoscopy. In questions with perceived or stated IT hypertrophy, the respondents chose to perform IT reduction significantly more frequently when the perceived or stated adenoid hypertrophy was less severe (p < 0.0001 for video and p = 0.039 for written questions). CONCLUSION: The decision to perform IT reduction in children is inversely related to the extent of adenoid hypertrophy. Future studies on pediatric IT surgery should include objective descriptions of the IT and adenoid in study subjects. PMID- 27196624 TI - Systematic variation of acquisition rate in delay eyelid conditioning. AB - Averaging artifacts inherent in group acquisition curves can mask behavioral phenomena that are potentially revealing in terms of underlying neural mechanisms. To address this, we implemented a behavioral analysis of 106 rabbits trained over 4 sessions using delay eyelid conditioning. Group results showed the typical monotonic increase in conditioned responses (CRs). For most subjects CRs first appeared (as indexed by the criterion of 8 CRs in 9 trials) during the first 18 trials of the second training session. Subdividing subjects according to the training block at which they met criterion revealed systematic differences in the subsequent rate that CR amplitudes increased, but not in asymptotic CR amplitudes. Subjects meeting criterion early in sessions showed more rapid increases in CR amplitude than those meeting criterion later in sessions. This effect was solely dependent on how early within a session criterion was met, as subjects meeting criterion at the beginning of the third and fourth sessions showed more rapid increases in CR amplitude than those meeting criterion after the first 18 trials of the second session. The exceptions were the 7% of the subjects that met criterion late in the first session. Their CR amplitudes increased at a rate similar to subjects meeting criterion early in sessions. These results suggest an interplay between consolidation processes and a previously reported short-term plasticity process that makes CR acquisition a nonmonotonic and complex function of the point during training sessions at which CRs first appear. (PsycINFO Database Record PMID- 27196623 TI - Relating approach-to-target and detection tasks in animal psychoacoustics. AB - Psychophysical experiments seek to measure the limits of perception. While straightforward in humans, in animals they are time consuming. Choosing an appropriate task and interpreting measurements can be challenging. We investigated the localization of high-frequency auditory signals in noise using an "approach-to-target" task in ferrets, how task performance should be interpreted in terms of perception, and how the measurements relate to other types of tasks. To establish their general ability to localize, animals were first trained to discriminate broadband noise from 12 locations. Subsequently we tested their ability to discriminate between band-limited targets at 2 or 3 more widely spaced locations, in a continuous background noise. The ability to discriminate between 3 possible locations (-90 degrees , 0 degrees , 90 degrees ) of a 10-kHz pure tone decreased gradually over a wide range (>30 dB) of signal-to noise ratios (SNRs). Location discrimination ability was better for wide band noise targets (0.5 and 2 octave). These results were consistent with localization ability limiting performance for pure tones. Discrimination of pure tones at 2 locations (-90/left, 90/right) was robust at positive SNRs, yielding psychometric functions which fell steeply at negative SNRs. Thresholds for discrimination were similar to previous tone-in-noise thresholds measured in ferrets using a yes/no task. Thus, using an approach-to-target task, sound "localization" in noise can reflect detectability or the ability to localize, depending on the stimulus configuration. Signal-detection-theory-based models were able to account for the results when discriminating between pure tones from 2- and 3-source locations. (PsycINFO Database Record PMID- 27196626 TI - Low-Level Laser for Mitigation of Low Salivary Flow Rate in Head and Neck Cancer Patients Undergoing Radiochemotherapy: A Prospective Longitudinal Study. AB - OBJECTIVE: The present study aimed to assess the impact of low-level laser (LLL) on low salivary flow rate in patients undergoing radiochemotherapy (RT-CT) for head and neck cancer. BACKGROUND DATA: LLL has shown efficiency in preventing hyposalivation in patients under different pathological conditions, including those undergoing RT-CT. METHODS: During all RT-CT, 17 patients received laser therapy and 10 received clinical care only. An Indium-Gallium-Aluminum-Phosphorus diode laser was punctually used for intraoral (660 nm, 40 mW, 10 J/cm(2), illuminated area 0.04 cm(2), 10 sec) and extraoral irradiation (780 nm, 15 mW, 3.8 J/cm(2), illuminated area 0.04 cm(2), 10 sec), three times a week and on alternate days, for a total of 21 sessions. Unstimulated salivary flow rate was assessed before the first RT session (N0), at the 15th RT session (N15), at the last RT session (Nf), and at 30 (N30) and 90 days after the end of the oncologic treatment (N90). RESULTS: At N15, Nf, and N30, patients treated with LLL showed significantly higher averages of salivary flow rate when compared with patients receiving clinical care only. CONCLUSIONS: LLL seems to be an efficient tool for mitigation of salivary hypofunction in patients undergoing RT for head and neck cancer. PMID- 27196627 TI - Uptake of Isoniazid Preventive Therapy among Under-Five Children: TB Contact Investigation as an Entry Point. AB - A child's risk of developing tuberculosis (TB) can be reduced by nearly 60% with administration of 6 months course of isoniazid preventive therapy (IPT). However, uptake of IPT by national TB programs is low, and IPT delivery is a challenge in many resource-limited high TB-burden settings. Routinely collected program data was analyzed to determine the coverage and outcome of implementation of IPT for eligible under-five year old children in 28 health facilities in two regions of Ethiopia. A total of 504 index smear-positive pulmonary TB (SS+) cases were reported between October 2013 and June 2014 in the 28 health facilities. There were 282 under-five children registered as household contacts of these SS+ TB index cases, accounting for 17.9% of all household contacts. Of these, 237 (84%) were screened for TB symptoms, and presumptive TB was identified in 16 (6.8%) children. TB was confirmed in 5 children, producing an overall yield of 2.11% (95% confidence interval, 0.76-4.08%). Of 221 children eligible for IPT, 64.3% (142) received IPT, 80.3% (114) of whom successfully completed six months of therapy. No child developed active TB while on IPT. Contact screening is a good entry point for delivery of IPT to at risk children and should be routine practice as recommended by the WHO despite the implementation challenges. PMID- 27196628 TI - Titanium Oxide Crystallization and Interface Defect Passivation for High Performance Insulator-Protected Schottky Junction MIS Photoanodes. AB - Atomic layer deposited (ALD) TiO2 protection layers may allow for the development of both highly efficient and stable photoanodes for solar fuel synthesis; however, the very different conductivities and photovoltages reported for TiO2 protected silicon anodes prepared using similar ALD conditions indicate that mechanisms that set these key properties are, as yet, poorly understood. In this report, we study hydrogen-containing annealing treatments and find that postcatalyst-deposition anneals at intermediate temperatures reproducibly yield decreased oxide/silicon interface trap densities and high photovoltage. A previously reported insulator thickness-dependent photovoltage loss in metal insulator-semiconductor Schottky junction photoanodes is suppressed. This occurs simultaneously with TiO2 crystallization and an increase in its dielectric constant. At small insulator thickness, a record for a Schottky junction photoanode of 623 mV photovoltage is achieved, yielding a photocurrent turn-on at 0.92 V vs NHE or -0.303 V with respect to the thermodynamic potential for water oxidation. PMID- 27196629 TI - Psychosocial, clinical and demographic features related to worry in patients with melanoma. AB - The aim of this study was to investigate clinical, demographic and psychosocial predictors of melanoma-related worry. A questionnaire-based study in a population ascertained cohort of individuals diagnosed with melanoma in the previous 3-6 months was carried out to identify factors associated with worry about melanoma shortly after diagnosis. A total of 520 patients felt worried about their future with respect to melanoma and 1568 patients felt confident about their future with respect to melanoma. Worry was less likely in men with partners than women with partners [adjusted odds ratio (OR)=0.51, 95% confidence interval (CI) (0.39 0.67)], and increasing age was protective against worry [adjusted OR=0.96 per year, 95% CI (0.95-0.97)]. Worry was more likely for patients with stage III/IV melanoma [adjusted OR=1.90, 95% CI (1.41-2.56) compared with stages IB-IIC], melanoma arising in sun-protected sites (compared with a limb), no occupation (compared with workers), those who reported insufficient emotional support from healthcare providers [adjusted OR=2.20, 95% CI (1.56-3.09) compared with sufficient support], lower knowledge of melanoma [adjusted OR=4.50, 95% CI (2.82 7.18) compared with well informed], perceived financial hardship compared with no financial hardship and over three previous negative life events compared with none/one. Worry about melanoma outcomes after diagnosis is multifactorial in origin. PMID- 27196630 TI - rRNA Gene Expression of Abundant and Rare Activated-Sludge Microorganisms and Growth Rate Induced Micropollutant Removal. AB - The role of abundant and rare taxa in modulating the performance of wastewater treatment systems is a critical component of making better predictions for enhanced functions such as micropollutant biotransformation. In this study, we compared 16S rRNA genes (rDNA) and rRNA gene expression of taxa in an activated sludge-treatment plant (sequencing batch membrane bioreactor) at two solids retention times (SRTs): 20 and 5 days. These two SRTs were used to influence the rates of micropollutant biotransformation and nutrient removal. Our results show that rare taxa (<1%) have disproportionally high ratios of rRNA to rDNA, an indication of higher protein synthesis, compared to abundant taxa (>=1%) and suggests that rare taxa likely play an unrecognized role in bioreactor performance. There were also significant differences in community-wide rRNA expression signatures at 20-day SRT: anaerobic-oxic-anoxic periods were the primary driver of rRNA similarity. These results indicate differential expression of rRNA at high SRTs, which may further explain why high SRTs promote higher rates of micropollutant biotransformation. An analysis of micropollutant associated degradation genes via metagenomics and direct measurements of a suite of micropollutants and nutrients further corroborates the loss of enhanced functions at 5-day SRT operation. This work advances our knowledge of the underlying ecosystem properties and dynamics of abundant and rare organisms associated with enhanced functions in engineered systems. PMID- 27196631 TI - Cyto/Genotoxic Effects of Pistacia atlantica Resin, a Traditional Gum. AB - In recent years, many researchers have focused on native plants to search for a new source of natural components with medical approach, especially by means of anticancer potential. One of these natural components is Saqez, the resin of Pistacia atlantica sub-kurdica with the local name of Baneh. It has been reported as an anticancer and apoptosis inducer component; therefore, in this research, we aimed to evaluate the solvated resin's possible cyto/genotoxic effects. The cell viability was assessed using MTT assay. Flow cytometry analysis was performed to distinguish the role of apoptosis and necrosis in cell toxicity, which was further confirmed by Comet and DNA ladder assay, and 4,6-diamidino2-phenylindole (DAPI) staining. Pistacia atlantica's resin decreased the growth of the treated cells in a dose- and time-dependent manner, and single-strand DNA breaks have been observed through comet assay. Moreover, morphological changes of DAPI stained cells showed fragmentation in the nucleus of resin-treated cells. In addition, early and late apoptosis in the treated cells was determined by flow cytometry analysis, also DNA ladder assay showed fragmentation in DNA of the treated cells. This study has revealed that the resin has significant cyto/genotoxic effects on cancerous and noncancerous cell lines. Our results show that apoptosis and necrosis are the dominant mechanisms by which the resin affects cell lines. Although the resin of P. atlantica is the main source of mastic gum and has been used for a long time as a natural remedy for different diseases, it is necessary to perform thorough analysis due to its cyto/genotoxicity in vivo. PMID- 27196632 TI - Ionic liquid based polymeric liposomes: A stable and biocompatible soft platform for bioelectrochemistry. AB - Polymeric liposomes (denoted as ILs-polysomes) are a biocompatible and conductive nanomaterial, which was first utilised as the electrode material for immobilising and biosensing redox enzyme horseradish peroxide (HRP). The morphology and surface property of IL-polysomes was characterised and systematically compared with unpolymerised ionic liquid based liposomes (denoted as ILs-liposomes). Differing from IL-liposomes, IL-polysomes preserves their original morphology and bilayer membrane structure on glassy carbon (GC) electrodes due to the cross linking of polymerised lipids, thus exhibiting excellent stability and specific biocompability. Because of the existence of imidazolium ionic liquid moieties on the outer surface, IL-polysomes displays a positive charge in aqueous solution, leading to oppositely charged HRP self-assembling onto the vesicles to form HRP/IL-polysomes/PVA/GC electrodes. Owing to the combined merits of ILs and liposomes, electron transfer between HRP-Fe(III)/Fe(II) redox couples of immobilised enzymes and GC electrodes can be achieved. Therefore, HRP/IL polysomes/PVA/GC electrodes exhibited good electrocatalytic performance toward the electrocatalysis of H2O2. Accordingly, IL-polysomes could act as an efficient charged platform for the self-assembled redox enzymes to realise direct electrochemistry. IL-polysomes have a promising application in the fabrication of third-generation electrochemical biosensors. PMID- 27196633 TI - Self-Generated Electrokinetic Fluid Flows during Pseudomorphic Mineral Replacement Reactions. AB - Pseudomorphic mineral replacement reactions involve one mineral phase replacing another, while preserving the original mineral's size and texture. Macroscopically, these transformations are driven by system-wide equilibration through dissolution and precipitation reactions. It is unclear, however, how replacement occurs on the molecular scale and what role dissolved ion transport plays. Here, we develop a new quantitative framework to explain the pseudomorphic replacement of KBr crystal in a saturated KCl solution through a combination of microscopic, spectroscopic, and modeling techniques. Our observations reveal that pseudomorphic mineral replacement (pMRR) is transport-controlled for this system and that convective fluid flows, caused by diffusioosmosis, play a key role in the ion transport process across the reaction-induced pores in the product phase. Our findings have important implications for understanding mineral transformations in natural environments and suggest that replacement could be exploited in commercial and laboratory applications. PMID- 27196634 TI - The economic considerations of patients and caregivers in choice of dialysis modality. AB - Introduction Broader adoption of home dialysis could lead to considerable cost savings for health services. Globally, however, uptake remains low. The aim of this study was to describe patient and caregiver perspectives of the economic considerations that influence dialysis modality choice, and elicit policy relevant recommendations. Methods Semistructured interviews with predialysis or dialysis patients and their caregivers, at three hospitals in New Zealand. Interview transcripts were analyzed thematically. Findings 43 patients and 9 caregivers (total n = 52) participated. The three themes related to economic considerations were: (i) productivity losses associated with changes in employment; (ii) the need for personal subsidization of home dialysis expenses; and (iii) the role of socio-economic disadvantage as a barrier to home dialysis. Patients weighed the flexibility of home dialysis which allowed them to remain employed, against time required for training and out-of-pocket costs. Patients saw the lack of reimbursement of home dialysis costs as unjust and suggested that reimbursement would incentivize home dialysis uptake. Social disadvantage was a barrier to home dialysis as patients' housing was often unsuitable; they could not afford the additional treatment costs. Home hemodialysis was considered to have the highest out-of-pocket costs and was sometimes avoided for this reason. Discussion Our data suggests that economic considerations underpin the choices patients make about dialysis treatments, however these are rarely reported. To promote home dialysis, strategies to improve employment retention and housing, and to minimize out-of-pocket costs, need to be addressed directly by healthcare providers and payers. PMID- 27196635 TI - Correlating Cleaning Thoroughness with Effectiveness and Briefly Intervening to Affect Cleaning Outcomes: How Clean Is Cleaned? AB - OBJECTIVES: The most efficient approach to monitoring and improving cleaning outcomes remains unresolved. We sought to extend the findings of a previous study by determining whether cleaning thoroughness (dye removal) correlates with cleaning efficacy (absence of molecular or cultivable biomaterial) and whether one brief educational intervention improves cleaning outcomes. DESIGN: Before after trial. SETTING: Newly built community hospital. INTERVENTION: 90 minute training refresher with surface-specific performance results. METHODS: Dye removal, measured by fluorescence, and biomaterial removal and acquisition, measured with culture and culture-independent PCR-based assays, were clandestinely assessed for eight consecutive months. At this midpoint, results were presented to the cleaning staff (intervention) and assessments continued for another eight consecutive months. RESULTS: 1273 surfaces were sampled before and after terminal room cleaning. In the short-term, dye removal increased from 40.3% to 50.0% (not significant). For the entire study period, dye removal also improved but not significantly. After the intervention, the number of rooms testing positive for specific pathogenic species by culturing decreased from 55.6% to 36.6% (not significant), and those testing positive by PCR fell from 80.6% to 53.7% (P = 0.016). For nonspecific biomaterial on surfaces: a) removal of cultivable Gram-negatives (GN) trended toward improvement (P = 0.056); b) removal of any cultivable growth was unchanged but acquisition (detection of biomaterial on post-cleaned surfaces that were contaminant-free before cleaning) worsened (P = 0.017); c) removal of PCR-based detection of bacterial DNA improved (P = 0.046), but acquisition worsened (P = 0.003); d) cleaning thoroughness and efficacy were not correlated. CONCLUSION: At this facility, a minor intervention or minimally more aggressive cleaning may reduce pathogen-specific contamination, but not without unintended consequences. PMID- 27196637 TI - Optimizing cyanobacteria growth conditions in a sealed environment to enable chemical inhibition tests with volatile chemicals. AB - Cyanobacteria are currently being engineered to photosynthetically produce next generation biofuels and high-value chemicals. Many of these chemicals are highly toxic to cyanobacteria, thus strains with increased tolerance need to be developed. The volatility of these chemicals may necessitate that experiments be conducted in a sealed environment to maintain chemical concentrations. Therefore, carbon sources such as NaHCO3 must be used for supporting cyanobacterial growth instead of CO2 sparging. The primary goal of this study was to determine the optimal initial concentration of NaHCO3 for use in growth trials, as well as if daily supplementation of NaHCO3 would allow for increased growth. The secondary goal was to determine the most accurate method to assess growth of Anabaena sp. PCC 7120 in a sealed environment with low biomass titers and small sample volumes. An initial concentration of 0.5g/L NaHCO3 was found to be optimal for cyanobacteria growth, and fed-batch additions of NaHCO3 marginally improved growth. A separate study determined that a sealed test tube environment is necessary to maintain stable titers of volatile chemicals in solution. This study also showed that a SYTO(r) 9 fluorescence-based assay for cell viability was superior for monitoring filamentous cyanobacterial growth compared to absorbance, chlorophyll alpha (chl a) content, and biomass content due to its accuracy, small sampling size (100MUL), and high throughput capabilities. Therefore, in future chemical inhibition trials, it is recommended that 0.5g/L NaHCO3 is used as the carbon source, and that culture viability is monitored via the SYTO(r) 9 fluorescence-based assay that requires minimum sample size. PMID- 27196636 TI - Characterizing the in vitro biofilm phenotype of Staphylococcus epidermidis isolates from central venous catheters. AB - Central venous catheter (CVC)-related infections are commonly caused by Staphylococcus epidermidis that is able to form a biofilm on the catheter surface. Many studies involving biofilm formation by Staphylococcus have been published each adopting an own in vitro model. Since the capacity to form a biofilm depends on multiple environmental factors, direct comparison of results obtained in different studies remains challenging. This study characterized the phenotype (strong versus weak biofilm-producers) of S. epidermidis from CVCs in four different in vitro biofilm models, covering differences in material type (glass versus polymer) and nutrient presentation (static versus continuous flow). A good correlation in phenotype was obtained between glass and polymeric surfaces independent of nutrient flow, with 85% correspondence under static growth conditions and 80% under dynamic conditions. A 80% correspondence between static and dynamic conditions on polymeric surfaces could be demonstrated as well. Incubation time had a significant influence on the biofilm phenotype with only 55% correspondence between the dynamic models at different incubation times (48h versus 17h). Screening for the presence of biofilm-related genes only revealed that ica A was correlated with biofilm formation under static but not under dynamic conditions. In conclusion, this study highlights that a high level of standardization is necessary to interpret and compare results of different in vitro biofilm models. PMID- 27196638 TI - Development of a real-time PCR assay for quantification of Citrobacter rodentium. AB - Molecular tools to quantify Citrobacter rodentium are not available. We developed a quantitative PCR assay targeting the espB gene. This assay is specific, has a linearity range of about 6.7*10(1) to 6.7*10(6)cells/PCR reaction (92% efficiency) and a detection limit of about 10(4)cells/g wet feces. PMID- 27196639 TI - Endothelial dysfunction and arterial stiffness in pre-eclampsia demonstrated by the EndoPAT method. AB - OBJECTIVES: The EndoPAT method has been used as a non-invasive method for assessing endothelial function in several non-pregnant populations. We investigated its possible use in assessing endothelial dysfunction in pre eclampsia. METHODS: Two hundred and fifteen participants were recruited and grouped as pre-eclamptic cases (105) and normotensive controls (110). Endothelial function and arterial stiffness were measured as reactive hyperaemia index and augmentation index, respectively, using the EndoPAT 2000 machine. RESULTS: The reactive hyperaemia index was significantly lower in the pre-eclamptic group compared to the normotensive group (p < 0.05). Augmentation index on the other hand was significantly higher in the pre-eclamptic group compared to the normotensive group (p < 0.0001). CONCLUSION: The EndoPAT method demonstrates endothelial dysfunction and arterial stiffness in pre-eclampsia. PMID- 27196640 TI - Counterproductive Consequences of a Conservative Ideology: Medicaid Expansion and Personal Responsibility Requirements. AB - Medicaid expansion, a key part of the Affordable Care Act, has been opposed by conservative politicians despite its fiscal and public health benefits. In response, some Republican-led states have expanded Medicaid with new reforms, including requirements for cost sharing and behavioral incentives, that promote conservative political values tied to an ideology of personal responsibility. We examine this trend using Michigan's Medicaid expansion as a case example. We explore the origins, evidence base, and possible consequences of these reforms. We argue that these reforms prioritize ideology over sound public health knowledge, deflecting attention away from the social, economic, and structural factors that influence the health of the poor, and may ultimately contribute to counterproductive public health and fiscal outcomes. PMID- 27196641 TI - Emotional Feedback and the Viral Spread of Social Media Messages About Autism Spectrum Disorders. AB - OBJECTIVE: To determine whether exchanges of emotional language between health advocacy organizations and social media users predict the spread of posts about autism spectrum disorders (ASDs). METHODS: I created a Facebook application that tracked views of ASD advocacy organizations' posts between July 19, 2011, and December 18, 2012. I evaluated the association between exchanges of emotional language and viral views of posts, controlling for additional characteristics of posts, the organizations that produced them, the social media users who viewed them, and the broader social environment. RESULTS: Exchanges of emotional language between advocacy organizations and social media users are strongly associated with viral views of posts. CONCLUSIONS: Social media outreach may be more successful if organizations invite emotional dialogue instead of simply conveying information about ASDs. Yet exchanges of angry language may contribute to the viral spread of misinformation, such as the rumor that vaccines cause ASDs. PMID- 27196642 TI - Evaluation of American Indian Health Service Training in Pain Management and Opioid Substance Use Disorder. AB - We examined the benefits of a collaboration between the Indian Health Service and an academic medical center to address the high rates of unintentional drug overdose in American Indians/Alaska Natives. In January 2015, the Indian Health Service became the first federal agency to mandate training in pain and opioid substance use disorder for all prescribing clinicians. More than 1300 Indian Health Service clinicians were trained in 7 possible 5-hour courses specific to pain and addiction. We noted positive changes in pre- and postcourse knowledge, self-efficacy, and attitudes as well as thematic responses showing the trainings to be comprehensive, interactive, and convenient. PMID- 27196643 TI - Firearm Ownership and Suicide Rates Among US Men and Women, 1981-2013. AB - OBJECTIVES: To examine the relationship between state-level firearm ownership rates and gender-specific, age-adjusted firearm and total suicide rates across all 50 US states from 1981 to 2013. METHODS: We used panel data for all 50 states that included annual overall and gender-specific suicide and firearm suicide rates and a proxy for state-level household firearm ownership. We analyzed data by using linear regression and generalized estimating equations to account for clustering. RESULTS: State-level firearm ownership was associated with an increase in both male and female firearm-related suicide rates and with a decrease in nonfirearm-related suicide rates. Higher gun ownership was associated with higher suicide rates by any means among male, but not among female, persons. CONCLUSIONS: We found a strong relationship between state-level firearm ownership and firearm suicide rates among both genders, and a relationship between firearm ownership and suicides by any means among male, but not female, individuals. POLICY IMPLICATIONS: For male persons, policies that reduce firearm ownership will likely reduce suicides by all means and by firearms. For female persons, such policies will likely reduce suicides by firearms. PMID- 27196644 TI - Impact of Food Assistance Programs on Obesity in Mothers and Children: A Prospective Cohort Study in Peru. AB - OBJECTIVES: To assess obesity risk among mothers participating in Community Kitchens and children participating in Glass of Milk (Peru food assistance programs). METHODS: We analyzed prospective data from the Young Lives study. The exposure consisted in varying degrees of benefit from any of the programs (no participation in any of the programs, program participation for some months, or program participation nearly every month) at baseline (2006-2007). The outcome was overweight and obesity in mothers and children at follow-up (2009-2010). RESULTS: Prevalence of childhood overweight and obesity was 15.5% and 5.1%, respectively; the corresponding figures for mothers were 40.5% and 14.6%. Children exposed nearly every month to the Glass of Milk program had a 65% lower risk of becoming obese compared with children not participating in the program (relative risk [RR] = 0.35; 95% confidence interval [CI] = 0.18, 0.66). Mothers participating frequently in the Community Kitchens program had almost twice the risk of becoming obese compared with those who did not participate (RR = 1.93; 95% CI = 1.18, 3.15). CONCLUSIONS: Participating in food assistance programs in Peru was associated with a lower risk of obesity in children and greater risk of obesity in mothers. PMID- 27196646 TI - Access and Quality of Care by Insurance Type for Low-Income Adults Before the Affordable Care Act. AB - OBJECTIVES: To compare access to care and perceived health care quality by insurance type among low-income adults in 3 southern US states, before Medicaid expansion under the Affordable Care Act. METHODS: We conducted a telephone survey in 2013 of 2765 low-income US citizens, aged 19 to 64 years, in Arkansas, Kentucky, and Texas. We compared 11 measures of access and quality of care for respondents with Medicaid, private insurance, Medicare, and no insurance with adjustment for sociodemographics and health status. RESULTS: Low-income adults with Medicaid, private insurance, and Medicare reported significantly better health care access and quality than uninsured individuals. Medicaid beneficiaries reported greater difficulty accessing specialists but less risk of high out-of pocket spending than those with private insurance. For other outcomes, Medicaid and private coverage performed similarly. CONCLUSIONS: Low-income adults with insurance report significantly greater access and quality of care than uninsured adults, regardless of whether they have private or public insurance. Access to specialty care in Medicaid may require policy attention. PUBLIC HEALTH IMPLICATIONS: Many states are still considering whether to expand Medicaid under the Affordable Care Act and whether to pursue alternative models for coverage expansion. Our results suggest that access to quality health care will improve under the Affordable Care Act's coverage expansions, regardless of the type of coverage. PMID- 27196645 TI - Peer Support for the Hardly Reached: A Systematic Review. AB - BACKGROUND: Health disparities are aggravated when prevention and care initiatives fail to reach those they are intended to help. Groups can be classified as hardly reached according to a variety of circumstances that fall into 3 domains: individual (e.g., psychological factors), demographic (e.g., socioeconomic status), and cultural-environmental (e.g., social network). Several reports have indicated that peer support is an effective means of reaching hardly reached individuals. However, no review has explored peer support effectiveness in relation to the circumstances associated with being hardly reached or across diverse health problems. OBJECTIVES: To conduct a systematic review assessing the reach and effectiveness of peer support among hardly reached individuals, as well as peer support strategies used. SEARCH METHODS: Three systematic searches conducted in PubMed identified studies that evaluated peer support programs among hardly reached individuals. In aggregate, the searches covered articles published from 2000 to 2015. SELECTION CRITERIA: Eligible interventions provided ongoing support for complex health behaviors, including prioritization of hardly reached populations, assistance in applying behavior change plans, and social-emotional support directed toward disease management or quality of life. Studies were excluded if they addressed temporally isolated behaviors, were limited to protocol group classes, included peer support as the dependent variable, did not include statistical tests of significance, or incorporated comparison conditions that provided appreciable social support. DATA COLLECTION AND ANALYSIS: We abstracted data regarding the primary health topic, categorizations of hardly reached groups, program reach, outcomes, and strategies employed. We conducted a 2-sample t test to determine whether reported strategies were related to reach. RESULTS: Forty-seven studies met our inclusion criteria, and these studies represented each of the 3 domains of circumstances assessed (individual, demographic, and cultural-environmental). Interventions addressed 8 health areas, most commonly maternal and child health (25.5%), diabetes (17.0%), and other chronic diseases (14.9%). Thirty-six studies (76.6%) assessed program reach, which ranged from 24% to 79% of the study population. Forty-four studies (94%) reported significant changes favoring peer support. Eleven strategies emerged for engaging and retaining hardly reached individuals. Among them, programs that reported a strategy of trust and respect had higher participant retention (82.8%) than did programs not reporting such a strategy (48.1%; P = .003). In 5 of the 6 studies examining moderators of the effects of peer support, peer support benefits were greater among individuals characterized by disadvantage (e.g., low health literacy). CONCLUSIONS: Peer support is a broad and robust strategy for reaching groups that health services too often fail to engage. The wide range of audiences and health concerns among which peer support is successful suggests that a basis for its success may be its flexible response to different contexts, including the intended audience, health problems, and setting. PUBLIC HEALTH IMPLICATIONS: The general benefits of peer support and findings suggesting that it may be more effective among those at heightened disadvantage indicate that peer support should be considered in programs intended to reach and benefit those too often hardly reached. Because engendering trust and respect was significantly associated with participant retention, programs should emphasize this strategy. PMID- 27196648 TI - Calorie Underestimation When Buying High-Calorie Beverages in Fast-Food Contexts. AB - We asked 1877 adults and 1178 adolescents visiting 89 fast-food restaurants in New England in 2010 and 2011 to estimate calories purchased. Calorie underestimation was greater among those purchasing a high-calorie beverage than among those who did not (adults: 324 +/-698 vs 102 +/-591 calories; adolescents: 360 +/-602 vs 198 +/-509 calories). This difference remained significant for adults but not adolescents after adjusting for total calories purchased. Purchasing high-calorie beverages may uniquely contribute to calorie underestimation among adults. PMID- 27196647 TI - Family-Focused Preventive Interventions With Cancer Cosurvivors: A Call to Action. AB - Health promotion and preventive action in the context of public health interventions for highly prevalent, long-term conditions such as cancer are rarely geared toward the family as a whole. Yet family members, as cancer cosurvivors, must manage their own substantial stress and multiple caregiving responsibilities and often constitute a critical nexus between individual patients and clinicians. We drew on 2 examples of cancer cosurvivorship from 2 different health service contexts, the United States and Finland. A systemic approach in public health is needed to support family members who not only have to confront the meaning of long-term conditions such as cancer but also may have to manage concurrent social life challenges and stressors such as economic hardship. PMID- 27196649 TI - Challenges in Identifying Refugees in National Health Data Sets. AB - OBJECTIVES: To evaluate publicly available data sets to determine their utility for studying refugee health. METHODS: We searched for keywords describing refugees in data sets within the Society of General Internal Medicine Dataset Compendium and the Inter-University Consortium for Political and Social Research database. We included in our analysis US-based data sets with publicly available documentation and a self-defined, health-related focus that allowed for an examination of patient-level factors. RESULTS: Of the 68 data sets that met the study criteria, 37 (54%) registered keyword matches related to refugees, but only 2 uniquely identified refugees. CONCLUSIONS: Few health data sets identify refugee status among participants, presenting barriers to understanding refugees' health and health care needs. PUBLIC HEALTH IMPLICATIONS: Information about refugee status in national health surveys should include expanded demographic questions and focus on mental health and chronic disease. PMID- 27196650 TI - Population Survey Features and Response Rates: A Randomized Experiment. AB - OBJECTIVES: To study the effects of several survey features on response rates in a general population health survey. METHODS: In 2012 and 2013, 8000 households in British Columbia, Canada, were randomly allocated to 1 of 7 survey variants, each containing a different combination of survey features. Features compared included administration modes (paper vs online), prepaid incentive ($2 coin vs none), lottery incentive (instant vs end-of-study), questionnaire length (10 minutes vs 30 minutes), and sampling frame (InfoCanada vs Canada Post). RESULTS: The overall response rate across the 7 groups was 27.9% (range = 17.1-43.4). All survey features except the sampling frame were associated with statistically significant differences in response rates. The survey mode elicited the largest effect on the odds of response (odds ratio [OR] = 2.04; 95% confidence interval [CI] = 1.61, 2.59), whereas the sampling frame showed the least effect (OR = 1.14; 95% CI = 0.98, 1.34). The highest response was achieved by mailing a short paper survey with a prepaid incentive. CONCLUSIONS: In a mailed general population health survey in Canada, a 40% to 50% response rate can be expected. Questionnaire administration mode, survey length, and type of incentive affect response rates. PMID- 27196651 TI - Academic Dysfunction After a Concussion Among US High School and College Students. AB - OBJECTIVES: To determine whether concussed students experience greater academic dysfunction than students who sustain other injuries. METHODS: We conducted a prospective cohort study from September 2013 through January 2015 involving high school and college students who visited 3 emergency departments in the Rochester, New York, area. Using telephone surveys, we compared self-reported academic dysfunction between 70 students with concussions and a comparison group of 108 students with extremity injuries at 1 week and 1 month after injury. RESULTS: At 1 week after injury, academic dysfunction scores were approximately 16 points higher (b = 16.20; 95% confidence interval = 6.39, 26.00) on a 174-point scale in the concussed group than in the extremity injury group. Although there were no differences overall at 1-month after injury, female students in the concussion group and those with a history of 2 or more prior concussions were more likely to report academic dysfunction. CONCLUSIONS: Our results showed academic dysfunction among concussed students, especially female students and those with multiple prior concussions, 1 week after their injury. Such effects appeared to largely resolve after 1 month. Our findings support the need for academic adjustments for concussed students. PMID- 27196652 TI - Quantitative Bias Analysis in Regulatory Settings. AB - Nonrandomized studies are essential in the postmarket activities of the US Food and Drug Administration, which, however, must often act on the basis of imperfect data. Systematic errors can lead to inaccurate inferences, so it is critical to develop analytic methods that quantify uncertainty and bias and ensure that these methods are implemented when needed. "Quantitative bias analysis" is an overarching term for methods that estimate quantitatively the direction, magnitude, and uncertainty associated with systematic errors influencing measures of associations. The Food and Drug Administration sponsored a collaborative project to develop tools to better quantify the uncertainties associated with postmarket surveillance studies used in regulatory decision making. We have described the rationale, progress, and future directions of this project. PMID- 27196653 TI - Effect of the Affordable Care Act on Racial and Ethnic Disparities in Health Insurance Coverage. AB - OBJECTIVES: To document how health insurance coverage changed for White, Black, and Hispanic adults after the Affordable Care Act (ACA) went into effect. METHODS: We used data from the American Community Survey from 2008 to 2014 to examine changes in the percentage of nonelderly adults who were uninsured, covered by Medicaid, or covered by private health insurance. In addition to presenting overall trends by race/ethnicity, we stratified the analysis by income group and state Medicaid expansion status. RESULTS: In 2013, 40.5% of Hispanics and 25.8% of Blacks were uninsured, compared with 14.8% of Whites. We found a larger gap in private insurance, which was partially offset by higher rates of public coverage among Blacks and Hispanics. After the main ACA provisions went into effect in 2014, coverage disparities declined slightly as the percentage of adults who were uninsured decreased by 7.1 percentage points for Hispanics, 5.1 percentage points for Blacks, and 3 percentage points for Whites. Coverage gains were greater in states that expanded Medicaid programs. CONCLUSIONS: The ACA has reduced racial/ethnic disparities in coverage, although substantial disparities remain. Further increases in coverage will require Medicaid expansion by more states and improved program take-up in states that have already done so. PMID- 27196654 TI - Pediatric Care Provider Density and Personal Belief Exemptions From Vaccine Requirements in California Kindergartens. AB - OBJECTIVES: To understand contextual associations between medical care providers pediatricians, family medical practitioners, and alternative medicine practitioners-and personal belief exemptions (PBEs) from mandated school entry vaccinations. METHODS: Data on kindergarten PBEs from the California Department of Public Health were analyzed for 2010, 2011, and 2012, with each school sorted into Primary Care Service Areas (PCSAs). Provider data from federal sources and state records of alternative medicine providers, alongside controls for school factors, were used to estimate panel models. RESULTS: Each 10% increase in the relative proportion of pediatricians in a given PCSA was associated with a statistically significant 11% decrease in PBE prevalence. The same increase in the proportion of family medical practitioners was associated with a 3.5% relative increase. Access to alternative medicine practitioners was also associated with a significantly higher PBE prevalence. CONCLUSIONS: Medical provider contexts are associated with PBEs, reflecting a combination of contextual effects and self-selection of families into schools and PCSAs that share their preferences. The geographic distribution of child primary care services may be a key factor in a school's health risk associated with lack of immunization or underimmunization. PMID- 27196655 TI - Health Care Visits as a Risk Factor for Tuberculosis in Taiwan: A Population Based Case-Control Study. AB - OBJECTIVES: To assess whether health care visits of nontuberculous patients are a risk factor for contracting tuberculosis. METHODS: We conducted a case-control study nested within the cohort of 1 million individuals from the health insurance database in Taiwan between 2003 and 2010. We identified incident cases of tuberculosis through International Classification of Diseases, Ninth Revision (ICD-9) codes and prescription of antituberculosis drugs. We identified 4202 case participants and 16 808 control participants matched by age, gender, and date of diagnosis to estimate the association between frequency of health care visits and incidence of tuberculosis. RESULTS: Frequency of health care visits was associated with increased risk of tuberculosis in a dose-dependent manner after adjustment for other medical comorbidities (P for trend < .001). Compared with individuals with fewer than 5 visits per year, those with more than 30 had a 77% increase in tuberculosis risk (adjusted odds ratio = 1.77; 95% confidence interval [CI] = 1.60, 1.97). CONCLUSIONS: Frequent health care visits of nontuberculous patients appear to be a risk factor for contracting tuberculosis. PUBLIC HEALTH IMPLICATIONS: Efforts should focus on educating the general population to avoid unnecessary hospital visits, strengthening active case finding, and intensifying infection control in all health care settings. PMID- 27196656 TI - Hepatitis C Screening of the "Birth Cohort" (Born 1945-1965) and Younger Inmates of New York City Jails. AB - OBJECTIVES: To examine uptake of screening for all individuals born between 1945 and 1965 (referred to by the Centers for Disease Control and Prevention as the "birth cohort") and outline preliminary HCV prevalence data in the New York City jail system. METHODS: Data were extracted from electronic health records for all individuals screened for HCV between June 13, 2013, and June 13, 2014, in New York City jails. We used the Abbott EIA 2.0 HCV antibody assay for testing. RESULTS: In the year of study, 56 590 individuals were incarcerated; 15.1% were born between 1945 and 1965, and 84.6% were born after 1965. HCV screening was completed for 64.1% of the birth cohort and for 11.1% born after 1965, with 55.1% and 43.8% of cases found in these groups, respectively. The overall seropositivity rate was 20.6%. CONCLUSIONS: Birth cohort screening in a large jail system identified many HCV cases, but HCV infection was common among younger age groups. PUBLIC HEALTH IMPLICATIONS: Universal screening may be warranted pending further study including cost-effectiveness analyses. PMID- 27196657 TI - Young People's More Permissive Views About Marijuana: Local Impact of State Laws or National Trend? AB - OBJECTIVES: To determine whether state medical marijuana laws "send the wrong message," that is, have a local influence on the views of young people about the risks of using marijuana. METHODS: We performed multilevel, serial, cross sectional analyses on 10 annual waves of the US National Survey on Drug Use and Health (2004-2013) nationally and for states with marijuana laws using individual and state-level controls. RESULTS: Living in medical marijuana states was associated with more permissive views regarding marijuana across 5 different measures. However, these associations became non-statistically significant after we adjusted for state-level differences. By contrast, there was a consistent and significant national time trend toward more permissive attitudes, which was less pronounced among children of middle school age than it was among their older counterparts. CONCLUSIONS: Passing medical marijuana laws does not seem to directly affect the views of young people in medical marijuana states. However, there is a national trend toward young people taking more permissive views about marijuana independent of any effects within states. PMID- 27196658 TI - Minimum Ages of Legal Access for Tobacco in the United States From 1863 to 2015. AB - In the United States, state laws establish a minimum age of legal access (MLA) for most tobacco products at 18 years. We reviewed the history of these laws with internal tobacco industry documents and newspaper archives from 1860 to 2014. The laws appeared in the 1880s; by 1920, half of states had set MLAs of at least 21 years. After 1920, tobacco industry lobbying eroded them to between 16 and 18 years. By the 1980s, the tobacco industry viewed restoration of higher MLAs as a critical business threat. The industry's political advocacy reflects its assessment that recruiting youth smokers is critical to its survival. The increasing evidence on tobacco addiction suggests that restoring MLAs to 21 years would reduce smoking initiation and prevalence, particularly among those younger than 18 years. PMID- 27196660 TI - Ten Things I Wish Someone Had Told Me When I Became a Health Officer. AB - Public health, like politics, is the art of the possible. To maximize effectiveness, public health officers in any jurisdiction should (1) get good data and ensure timely and effective dissemination; (2) prioritize and tackle more difficult initiatives first; (3) find, fight, and win winnable battles in areas where progress is possible but not ensured without focused, strategic effort; (4) support and hire great people and protect them so they can do their jobs; (5) address communicable diseases and environmental health effectively; (6) do not cede the clinical realm-public health programs depend on clinical care and on effective coordination between health care and public health; (7) learn and manage the budget cycle; (8) manage the context; (9) never surprise their boss; and (10) follow core principles. PMID- 27196661 TI - Mobilizing Local Authorities Around Public Health Priorities. AB - Large Analysis and Review of European Housing and Health Status (LARES) was conducted in Europe in 2002 to 2003 to study the relationship between citizens' health and built environments. One of its objectives was to put public health priorities on the agenda of local decision-makers to implement solutions for the community. We adapted the LARES protocol as a pilot project in a small French Canadian town in Quebec Province in 2012. The distinguishing feature of this project was the collaborative approach taken with local actors, especially the municipality, which was committed a priori to using survey data from an urban planning perspective. The project produced interesting results that were used to motivate actions concerning people living in bad sanitary conditions; to draft the urban plan including the development of parks, green spaces, and bicycle paths; and to allow the municipality to meet eligibility criteria for access to renovation programs. If a partnership with the local actors and their commitment to promote and realize the project were obtained at the beginning, then the survey could be replicated in other communities. PMID- 27196659 TI - Suicide Rates in Aboriginal Communities in Labrador, Canada. AB - OBJECTIVES: To compare suicide rates in Aboriginal communities in Labrador, including Innu, Inuit, and Southern Inuit, with the general population of Newfoundland, Canada. METHODS: In partnership with Aboriginal governments, we conducted a population-based study to understand patterns of suicide mortality in Labrador. We analyzed suicide mortality data from 1993 to 2009 from the Vital Statistics Death Database. We combined this with community-based methods, including consultations with Elders, youths, mental health and community workers, primary care clinicians, and government decision-makers. RESULTS: The suicide rate was higher in Labrador than in Newfoundland. This trend persisted across all age groups; however, the disparity was greatest among those aged 10 to 19 years. Males accounted for the majority of deaths, although suicide rates were elevated among females in the Inuit communities. When comparing Aboriginal subregions, the Innu and Inuit communities had the highest age-standardized mortality rates of, respectively, 165.6 and 114.0 suicides per 100 000 person-years. CONCLUSIONS: Suicide disproportionately affects Innu and Inuit populations in Labrador. Suicide rates were high among male youths and Inuit females. PMID- 27196662 TI - From Design to Dissemination: Implementing Community-Based Participatory Research in Postdisaster Communities. AB - OBJECTIVES: To review how disasters introduce unique challenges to conducting population-based research and community-based participatory research (CBPR). METHODS: From 2007-2009, we conducted the Head-off Environmental Asthma in Louisiana (HEAL) Study in the aftermath of Hurricane Katrina in a Gulf Coast community facing an unprecedented triple burden: Katrina's and other disasters' impact on the environment and health, historic health disparities, and persistent environmental health threats. RESULTS: The unique triple burden influenced every research component; still, most existing CBPR principles were applicable, even though full adherence was not always feasible and additional tailored principles govern postdisaster settings. CONCLUSIONS: Even in the most challenging postdisaster conditions, CBPR can be successfully designed, implemented, and disseminated while adhering to scientific rigor. PMID- 27196663 TI - Formative Work and Community Engagement Approaches for Implementing an HIV Intervention in Botswana Schools. AB - Providing adolescents with evidence-based sexual risk reduction interventions is critical to addressing the HIV/AIDS epidemic among adolescents in sub-Saharan Africa. Project AIM (Adult Identity Mentoring) is an innovative, evidence-based, youth development intervention that is being evaluated for the first time in Botswana through a 3-year (2015-2017), 50-school cluster randomized controlled trial, including testing for herpes simplex virus type 2 as a sexual activity biomarker. Conducting a trial of this magnitude requires the support and collaboration of government and community stakeholders. All school staff, including teachers, must be well informed about the study; dedicated staff placed at each school can help to improve school and community familiarity with the study, improve the information flow, and relieve some of the burden study activities places on schools. PMID- 27196665 TI - Electromyographic Analysis of the Lower Limb Muscles in Low- and High-Handicap Golfers. AB - PURPOSE: The aim of this study was to compare the electromyographic patterns of the lower limb muscles during a golf swing performed by low- and high-handicap golfers. METHOD: Ten golfers (5 low- and 5 high-handicap) performed 8 swings using a 7-iron. Surface electromyography (EMG) was recorded for the following lower limb muscles on both sides: biceps femoris, semitendinosus, gluteus maximus, vastus medialis and lateralis, rectus femoris, tibialis anterior, peroneus longus, and gastrocnemius medialis and lateralis. The golf-swing phases were determined by 3-dimensional high-speed video analysis. RESULTS: Compared with the high-handicap golfers, the low-handicap golfers performed the forward swing with a shorter duration of the swing phases, with the exception of the late follow-through, where they exhibited longer duration. Considering the EMG patterns, the low-handicap golfers showed a tendency for the studied muscles to reach an activation peak earlier and presented statistically significant higher muscle activity in some of the lower limb muscles, mainly from the left side. CONCLUSION: Differences between low- and high-handicap golfers were found in the average duration of swing phases and in the activation level of the lower limbs, with more evidence on muscles from the left side. PMID- 27196666 TI - The Evaluation of More Lymph Nodes in Colon Cancer Is Associated with Improved Survival in Patients of All Ages. AB - BACKGROUND: Improvement in survival of patients with colon cancer is reduced in elderly patients compared to younger patients. The aim of this study was to investigate whether the removal of >= 12 lymph nodes can explain differences in survival rates between elderly and younger patients diagnosed with colon cancer. METHODS: In a population-based cohort study, all patients (N = 41,074) diagnosed with colon cancer stage I to III from 2003 through 2010 from the Netherlands Cancer Registry were included. Age groups were defined as < 66, 66-75 and > 75 years of age. Main outcome measures were overall and relative survival, the latter as a proxy for disease specific survival. RESULTS: Over an eight years time period there was a 41.2% increase in patients with >= 12 lymph nodes removed, whereas the percentage of patients with the presence of lymph node metastases remained stable (35.7% to 37.5%). After adjustment for patient and tumour characteristics and adjuvant chemotherapy, it was found that for patients in which >= 12 lymph nodes were removed compared to patients with < 12 lymph nodes removed, there was a statistically significant higher overall survival (< 66: HR: 0.858 (95% CI, 0.789-0.933); 66-75: HR: 0.763 (95% CI, 0.714-0.814); > 75: HR: 0.734 (95% CI, 0.700-0.771)) and relative survival (< 66: RER: 0.783 (95% CI, 0.708-0.865); 66-75: RER: 0.672 (95% CI, 0.611-0.739); > 75: RER: 0.621 (95% CI, 0.567-0.681)) in all three age groups. CONCLUSIONS: The removal of >= 12 lymph nodes is associated with an improvement in both overall and relative survival in all patients. This association was stronger in the elderly patient. The biology of this association needs further clarification. PMID- 27196667 TI - Epidemiology of Hospital Admissions with Influenza during the 2013/2014 Northern Hemisphere Influenza Season: Results from the Global Influenza Hospital Surveillance Network. AB - BACKGROUND: The Global Influenza Hospital Surveillance Network was established in 2012 to obtain valid epidemiologic data on hospital admissions with influenza like illness. Here we describe the epidemiology of admissions with influenza within the Northern Hemisphere sites during the 2013/2014 influenza season, identify risk factors for severe outcomes and complications, and assess the impact of different influenza viruses on clinically relevant outcomes in at-risk populations. METHODS: Eligible consecutive admissions were screened for inclusion at 19 hospitals in Russia, Turkey, China, and Spain using a prospective, active surveillance approach. Patients that fulfilled a common case definition were enrolled and epidemiological data were collected. Risk factors for hospitalization with laboratory-confirmed influenza were identified by multivariable logistic regression. FINDINGS: 5303 of 9507 consecutive admissions were included in the analysis. Of these, 1086 were influenza positive (534 A(H3N2), 362 A(H1N1), 130 B/Yamagata lineage, 3 B/Victoria lineage, 40 untyped A, and 18 untyped B). The risk of hospitalization with influenza (adjusted odds ratio [95% confidence interval]) was elevated for patients with cardiovascular disease (1.63 [1.33-2.02]), asthma (2.25 [1.67-3.03]), immunosuppression (2.25 [1.23-4.11]), renal disease (2.11 [1.48-3.01]), liver disease (1.94 [1.18-3.19], autoimmune disease (2.97 [1.58-5.59]), and pregnancy (3.84 [2.48-5.94]). Patients without comorbidities accounted for 60% of admissions with influenza. The need for intensive care or in-hospital death was not significantly different between patients with or without influenza. Influenza vaccination was associated with a lower risk of confirmed influenza (adjusted odds ratio = 0.61 [0.48-0.77]). CONCLUSIONS: Influenza infection was detected among hospital admissions with and without known risk factors. Pregnancy and underlying comorbidity increased the risk of detecting influenza virus in patients hospitalized with influenza-like illness. Our results support influenza vaccination as a measure for reducing the risk of influenza-associated hospital admission. PMID- 27196669 TI - Body mass index and aromatase inhibitors: a step forward in individualizing therapy for breast cancer patients? AB - INTRODUCTION: Progress made in breast cancer management along with treatment related symptoms has drawn a lot of attention from both scientists and clinicians. Establishing predictive factors for treatment response facilitate tailoring of therapy to each individual patient and leads to a reduction in unnecessary treatments. Body mass index is confirmed to be a risk factor for breast cancer development as well as for disease recurrence, which additionally negatively influence the overall survival. Due to the increased level of fatty tissue in obese and overweight patients, their total level of body aromatase is elevated. This lead to the hypothesis about a worse response to aromatase inhibitors in these groups as compared to normal weight patients, due to incomplete aromatase blockage and thus higher peripheral androgen aromatization. AREAS COVERED: This review aims to summarize the data from clinical trials assessing the effect of BMI on response to AI-based therapy in the setting of breast cancer. Expert commentary: Our conclusion made on the data available to date does not exclude BMI from the list of potential predictive factors however further research in this area is warranted. PMID- 27196668 TI - Overcoming Resistance of Cancer Cells to PARP-1 Inhibitors with Three Different Drug Combinations. AB - Inhibitors of poly[ADP-ribose] polymerase 1 (PARPis) show promise for treatment of cancers which lack capacity for homologous recombination repair (HRR). However, new therapeutic strategies are required in order to overcome innate and acquired resistance to these drugs and thus expand the array of cancers that could benefit from them. We show that human cancer cell lines which respond poorly to ABT-888 (a PARPi), become sensitive to it when co-treated with vorinostat (a histone deacetylase inhibitor (HDACi)). Vorinostat also sensitized PARPis insensitive cancer cell lines to 6-thioguanine (6-TG)-a drug that targets PARPis sensitive cells. The sensitizing effect of vorinostat was associated with increased phosphorylation of eukaryotic initiation factor (eIF) 2alpha which in and of itself increases the sensitivity of cancer cells to ABT-888. Importantly, these drug combinations did not affect survival of normal fibroblasts and breast cells, and significantly increased the inhibition of xenograft tumor growth relative to each drug alone, without affecting the mice weight or their liver and kidney function. Our results show that combination of vorinostat and ABT-888 could potentially prove useful for treatment of cancer with innate resistance to PARPis due to active HRR machinery, while the combination of vorinostat and 6-TG could potentially overcome innate or acquired resistance to PARPis due to secondary or reversal BRCA mutations, to decreased PARP-1 level or to increased expression of multiple drug resistant proteins. Importantly, drugs which increase phosphorylation of eIF2alpha may mimic the sensitizing effect of vorinostat on cellular response to PARPis or to 6-TG, without activating all of its downstream effectors. PMID- 27196671 TI - Inhibition of the formation of benzo[a]pyrene adducts to DNA in A549 lung cells exposed to mixtures of polycyclic aromatic hydrocarbons. AB - Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous pollutants, which exhibit carcinogenic properties especially in lungs. In the present work, we studied the effect of mixtures of 12 PAHs on the A549 alveolar cells. We first assess the ability of each PAH at inducing gene expression of phase I metabolization enzymes and at generating DNA adducts. A good correlation was found between these two endpoints. We then exposed cells to either binary mixtures of the highly genotoxic benzo[a]pyrene (B[a]P) with each PAH or complex mixtures of all studied PAHs mimicking by real emissions including combustion of wood, cigarette smoke, and atmospheres of garage, silicon factory and urban environments. Compared to pure B[a]P, both types of mixtures led to reduced CYP450 activity measured by the EROD test. A similar trend was observed for the formation of DNA adducts. Surprisingly, the complex mixtures were more potent than B[a]P used at the same concentration for the induction of genes coding for CYP. Our results stress the lack of additivity of the genotoxic properties of PAH in mixtures. Interestingly, an opposite synergy in the formation of B[a]P adducts were observed previously in hepatocytes. Our data also show that measurement of the metabolic activity rather than quantification of gene expression reflects the actual bioactivation of PAHs into DNA damaging species. PMID- 27196670 TI - Involvement of DkTGA1 Transcription Factor in Anaerobic Response Leading to Persimmon Fruit Postharvest De-Astringency. AB - Persimmon fruit are unique in accumulating proanthocyanidins (tannins) during development, which cause astringency in mature fruit. In 'Mopanshi' persimmon, astringency can be removed by treatment with 95% CO2, which increases the concentrations of ethanol and acetaldehyde by glycolysis, and precipitates the soluble tannin. A TGA transcription factor, DkTGA1, belonging to the bZIP super family, was isolated from an RNA-seq database and real-time quantitative PCR indicated that DkTGA1 was up-regulated by CO2 treatment, in concert with the removal of astringency from persimmon fruit. Dual-luciferase assay revealed that DkTGA1 had a small (less than 2-fold), but significant effect on the promoters of de-astringency-related genes DkADH1, DkPDC2 and DkPDC3, which encode enzymes catalyzing formation of acetaldehyde and ethanol. A combination of DkTGA1 and a second transcription factor, DkERF9, shown previously to be related to de astringency, showed additive effects on the activation of the DkPDC2 promoter. Yeast one-hybrid assay showed that DkERF9, but not DkTGA1, could bind to the DkPDC2 promoter. Thus, although DkTGA1 expression is positively associated with persimmon fruit de-astringency, trans-activation analyses with DkPDC2 indicates it is likely to act by binding indirectly DkPDC2 promoter, might with helps of DkERF9. PMID- 27196672 TI - Atrial Conduction Velocity Correlates with Frequency Content of Bipolar Signal. AB - BACKGROUND: Anisotropy in conduction velocity (CV) is a key substrate abnormality influencing atrial arrhythmias. In skeletal muscle fibers, CV and frequency content of the surface electromyogram signal are directly related. We hypothesized that in human atria the frequency content of the bipolar signal, recorded on the endocardial surface, is directly related to the local CV. METHODS: In 15 patients submitted to ablation of supraventricular arrhythmias, incremental pacing was performed through an octapolar catheter inserted into the coronary sinus (CS), alternatively from both extremities in two different sequences: CS bipole 1-2 as the pacing site and CS bipole 7-8 as the detection site in the first, and vice versa in the second. The pacing cycle length (PCL) was stepwise decreased from 600 ms to 500 ms, 400 ms, 300 ms, until 250 ms. Estimation of the CV was performed as the ratio between the distance traveled by the propagating pulse and the propagation time. The frequency distribution of the signal energy was estimated using the fast Fourier transform, and the characteristic frequency (CF) was estimated as the barycenter of the frequency spectrum. RESULTS: A total of 2,496 bipolar signals were analyzed; CV and CF were estimated and compared. The single patient and group data analysis showed a significant direct correlation between CV and CF of the local bipolar signal. CONCLUSIONS: Comparing the degree of spectral compression among signals registered in different points of the endocardial cardiac surface in response to decreasing PCL enables to map local differences in CV, a useful arrhythmogenic substrate index. PMID- 27196674 TI - A Non-surgical Intervention for Triangular Fibrocartilage Complex Tears. AB - BACKGROUND AND PURPOSE: The current literature contains no reports of treatment options other than surgery following failed conservative management of a triangular fibrocartilage complex (TFCC) tear. The purpose of this study is to describe the use of a novel brace as a non-surgical intervention for TFCC tears. METHODS: This paper is a case study of a subject with a magnetic resonance imaging-confirmed TFCC tear. As an alternative to surgery, he consented to wear a novel brace for 12 weeks after conservative management of his injury had failed. His recovery from injury was monitored with a weight-bearing tolerance test and the disabilities of the arm, shoulder and hand (DASH) outcome measure. RESULTS: An increase in weight-bearing tolerance and upper extremity use was evident immediately after donning the brace. After 12 weeks, the subject demonstrated a return to normal weight-bearing tolerance and normal DASH outcome measure scores. These improvements were still evident at a 1-year follow-up appointment. DISCUSSION: Utilizing this novel brace resulted in functional status improvement in a subject with a TFCC tear as demonstrated by significant changes in his DASH outcome measure scores. This case study demonstrates the first non-surgical alternative treatment for a TFCC tear after conservative management has failed. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27196673 TI - Geno2pheno[HCV] - A Web-based Interpretation System to Support Hepatitis C Treatment Decisions in the Era of Direct-Acting Antiviral Agents. AB - The face of hepatitis C virus (HCV) therapy is changing dramatically. Direct acting antiviral agents (DAAs) specifically targeting HCV proteins have been developed and entered clinical practice in 2011. However, despite high sustained viral response (SVR) rates of more than 90%, a fraction of patients do not eliminate the virus and in these cases treatment failure has been associated with the selection of drug resistance mutations (RAMs). RAMs may be prevalent prior to the start of treatment, or can be selected under therapy, and furthermore they can persist after cessation of treatment. Additionally, certain DAAs have been approved only for distinct HCV genotypes and may even have subtype specificity. Thus, sequence analysis before start of therapy is instrumental for managing DAA based treatment strategies. We have created the interpretation system geno2pheno[HCV] (g2p[HCV]) to analyse HCV sequence data with respect to viral subtype and to predict drug resistance. Extensive reviewing and weighting of literature related to HCV drug resistance was performed to create a comprehensive list of drug resistance rules for inhibitors of the HCV protease in non structural protein 3 (NS3-protease: Boceprevir, Paritaprevir, Simeprevir, Asunaprevir, Grazoprevir and Telaprevir), the NS5A replicase factor (Daclatasvir, Ledipasvir, Elbasvir and Ombitasvir), and the NS5B RNA-dependent RNA polymerase (Dasabuvir and Sofosbuvir). Upon submission of up to eight sequences, g2p[HCV] aligns the input sequences, identifies the genomic region(s), predicts the HCV geno- and subtypes, and generates for each DAA a drug resistance prediction report. g2p[HCV] offers easy-to-use and fast subtype and resistance analysis of HCV sequences, is continuously updated and freely accessible under http://hcv.geno2pheno.org/index.php. The system was partially validated with respect to the NS3-protease inhibitors Boceprevir, Telaprevir and Simeprevir by using data generated with recombinant, phenotypic cell culture assays obtained from patients' virus variants. PMID- 27196676 TI - Benign Nerve Sheath Myxoma in an Infant Misdiagnosed as Infantile Digital Fibromatosis. AB - Herein we present the case of a 16-month boy, clinically diagnosed with infantile digital fibromatosis, but 9 months after continued growth, the mass was excised and the histopathologic diagnosis was that of a benign nerve sheath myxoma. We present this case to emphasize that nerve sheath myxomas (also known as myxoid neurothekeoma) should be included in the differential diagnosis of dermal nodules in infants. PMID- 27196675 TI - Resistance Analyses of Japanese Hepatitis C-Infected Patients Receiving Sofosbuvir or Ledipasvir/Sofosbuvir Containing Regimens in Phase 3 Studies. AB - High rates of sustained virologic response (SVR) has been achieved in Japanese patients with chronic hepatitis C virus (HCV) genotype (GT)1 and GT2 infection treated with ledipasvir/sofosbuvir (LDV/SOF) +/-ribavirin (RBV) and SOF+RBV, respectively. We evaluated the effect of baseline HCV NS5A and NS5B resistance associated variants (RAVs) on treatment outcome and characterized variants at virologic failure. Baseline deep sequencing for NS5A and NS5B genes was performed for all GT1 patients. Deep sequencing of NS5A (GT1 only) and NS5B (GT1 and GT2) was performed for patients who failed treatment or discontinued early with detectable HCV RNA (i.e., >25 IU/mL). In patients with HCV GT1 infection, 22.3% (GT1a: 2/11; GT1b: 74/330) had >=1 baseline NS5A RAV. The most frequent NS5A RAVs in GT1b were Y93H (17.9%, 59/330) and L31M (2.4%, 8/330). Despite the presence of NS5A RAVs at baseline, 100% and 97% of patients achieved SVR12, compared with 100% and 99% for those with no NS5A RAVs with LDV/SOF and LDV/SOF+RBV, respectively. All patients with NS5B RAVs at baseline achieved SVR12. Of the 153 patients with GT2 infection (GT2a 60.1%, GT2b 39.9%), 3.3% (5/153) experienced viral relapse. No S282T or other NS5B RAVs were detected at baseline or relapse; no change in susceptibility to SOF or RBV was observed at relapse. In conclusion, LDV/SOF and SOF+RBV demonstrate a high barrier to resistance in Japanese patients with HCV GT1 and GT2 infection. The presence of baseline NS5A RAVs did not impact treatment outcome in GT1 Japanese patients treated with LDV/SOF for 12 weeks. PMID- 27196677 TI - Legionella pneumophila strain associated with the first evidence of person-to person transmission of Legionnaires' disease: a unique mosaic genetic backbone. AB - A first strong evidence of person-to-person transmission of Legionnaires' Disease (LD) was recently reported. Here, we characterize the genetic backbone of this case-related Legionella pneumophila strain ("PtVFX/2014"), which also caused a large outbreak of LD. PtVFX/2014 is phylogenetically divergent from the most worldwide studied outbreak-associated L. pneumophila subspecies pneumophila serogroup 1 strains. In fact, this strain is also from serogroup 1, but belongs to the L. pneumophila subspecies fraseri. Its genomic mosaic backbone reveals eight horizontally transferred regions encompassing genes, for instance, involved in lipopolysaccharide biosynthesis or encoding virulence-associated Dot/Icm type IVB secretion system (T4BSS) substrates. PtVFX/2014 also inherited a rare ~65 kb pathogenicity island carrying virulence factors and detoxifying enzymes believed to contribute to the emergence of best-fitted strains in water reservoirs and in human macrophages, as well as a inter-species transferred (from L. oakridgensis) ~37.5 kb genomic island (harboring a lvh/lvr T4ASS cluster) that had never been found intact within L. pneumophila species. PtVFX/2014 encodes another lvh/lvr cluster near to CRISPR-associated genes, which may boost L. pneumophila transition from an environmental bacterium to a human pathogen. Overall, this unique genomic make-up may impact PtVFX/2014 ability to adapt to diverse environments, and, ultimately, to be transmitted and cause human disease. PMID- 27196678 TI - The Effect of Physician and Hospital Market Structure on Medical Technology Diffusion. AB - OBJECTIVE: To examine the influence of physician and hospital market structures on medical technology diffusion, studying the diffusion of drug-eluting stents (DESs), which became available in April 2003. DATA SOURCES/STUDY SETTING: Medicare claims linked to physician demographic data from the American Medical Association and to hospital characteristics from the American Hospital Association Survey. STUDY DESIGN: Retrospective claims data analyses. DATA COLLECTION/EXTRACTION METHODS: All fee-for-service Medicare beneficiaries who received a percutaneous coronary intervention (PCI) with a cardiac stent in 2003 or 2004. Each PCI record was joined to characteristics on the patient, the procedure, the cardiologist, and the hospital where the PCI was delivered. We accounted for the endogeneity of physician and hospital market structure using exogenous variation in the distances between patient, physician, and hospital locations. We estimated multivariate linear probability models that related the use of a DES in the PCI on market structure while controlling for patient, physician, and hospital characteristics. PRINCIPAL FINDINGS: DESs diffused faster in markets where cardiology practices faced more competition. Conversely, we found no evidence that the structure of the hospital market mattered. CONCLUSIONS: Competitive pressure to maintain or expand PCI volume shares compelled cardiologists to adopt DESs more quickly. PMID- 27196679 TI - Hepatocellular carcinoma in noncirrhotic livers is associated with steatosis rather than steatohepatitis: potential implications for pathogenesis. AB - OBJECTIVE: The risk of hepatocellular carcinoma (HCC) is increased in patients with metabolic syndrome (MS), possibly related to nonalcoholic fatty liver disease (NAFLD). As histological features of NAFLD may regress in cirrhosis, we compared steatosis versus steatohepatitis in the nontumoral liver of noncirrhotic HCC patients. PATIENTS AND METHODS: A retrospective clinicopathological analysis was carried out in 91 noncirrhotic HCC patients. Patients were divided into three subgroups: that is, patients with: (1) MS without other risk factors for underlying liver disease, (2) no underlying risk factors, or (3) other risk factors (with or without MS). The NAFLD activity score (NAS) less than 3 was classified as no steatohepatitis, NAS 3-4 as borderline steatohepatitis, and NAS 5 or more as definite steatohepatitis. RESULTS: Eleven (12%) patients had MS without other risk factors (group 1). In the nontumoral liver, significant steatosis (>=5% of hepatocytes) was generally present (in 10/11 patients), with mild lobular inflammation and absence of ballooning in most cases. Absence of steatohepatitis, borderline steatohepatitis, and definite steatohepatitis were found in 55, 45, and 0% of cases, respectively. In groups 2 and 3, significant steatosis was frequently present (in 16/37 and 21/43 patients, respectively). Absence of steatohepatitis, borderline steatohepatitis, and definite steatohepatitis were found in 84, 16, and 0% of cases (group 2), respectively, in 77, 23, and 0% of cases (group 3). CONCLUSION: In noncirrhotic HCC patients, histological steatosis was frequently present, whereas overt steatohepatitis did not occur. These findings may be relevant for HCC pathogenesis in NAFLD. PMID- 27196684 TI - Cadmium accumulation and tolerance of Lagerstroemia indica and Lagerstroemia fauriei (Lythraceae) seedlings for phytoremediation applications. AB - Contamination by heavy metals is one of the most serious environmental problems generated from human activities. Because phytoremediation utilizes plants to uptake contaminants, it could potentially be used to remediate metal-contaminated areas. A pot culture experiment with four levels of cadmium (Cd) (0, 20, 40, and 80 mg of Cd/kg dry soil) was conducted to investigate Cd accumulation and tolerance of roots, shoots, and leaves of Lagerstroemia indica and Lagerstroemia fauriei as well as their potential for phytoremediation. Experimental results indicated that Cd inhibited seedling growth only at the higher Cd exposure concentration (40 and 80 mg/kg). The tolerance index revealed that on average L. indica is more tolerant of Cd than L. fauriei. Moreover, plants in the experiment accumulated Cd differentially. In comparisons between L. indica and L. fauriei, the leaves of the former had higher concentrations of Cd, while the roots of latter had higher concentrations of Cd. Furthermore, the roots, shoots, and leaves had very high bioaccumulation factors that markedly exceeded 1.0 (exceptional only in shoots of 80 mg/kg for L. fauriei), indicating that the seedlings extracted Cd from the soil. The leaves' translocation factor of L. indica was greater than 1.0, being significantly higher than that of L. fauriei. Chlorophyll a, Chlorophyll b and total declined in both species significantly as Cd concentrations exceeded 40 mg/kg in the soil. In contrast, lipid peroxidation and proline content was found to increase with increasing Cd concentration. From the assessments of biomass production, Cd tolerance and uptake L. indica and L. fauriei could stand as excellent species for remediating Cd-contaminated soils. PMID- 27196685 TI - Interactions of Factors and Profiles of Incontinent Nursing Home Residents and Hospital Patients: A Classification Tree Analysis. AB - PURPOSE: To investigate the interactions among well-known influencing factors for urinary incontinence (UI), fecal incontinence (FI), and double urinary and fecal incontinence (DI) in the nursing home and hospital setting and to identify profiles of UI, FI, and DI residents and patients. SUBJECTS AND SETTING: Data from more than 4200 residents and patients from 16 nursing homes and 36 hospitals were collected. DESIGN: This was a cross-sectional study. METHODS: A cross sectional study was used for data collection. The Austrian version of the International Prevalence Measurement of Care Problems survey was used to collect data about different nursing care problems (eg, pressure ulcer and incontinence). To improve objectivity, 2 nurses assessed each resident/patient. The Care Dependency Scale (CDS) was used to measure the degree of care dependency regarding different needs such as mobility, with lower scores indicating a higher level of care dependency. A classification and regression tree analysis was used to determine the interactions among factors and develop profiles of incontinent residents and patients. RESULTS: Interactions between the CDS-items of states of Dress/Undress, Hygiene, Mobility, and Eat/Drink and age based on incontinence were found in nursing home residents. In contrast, interactions between the CDS items Hygiene and Eat/Drink, as well as age and gender based on incontinence, were identified in hospitalized patients. Residents with UI were care dependent with reference to the CDS-item Dress/Undress. Patients with UI were older than 77.5 years and completely, or to a great extent, care dependent with reference to the CDS-item Hygiene. Nursing home residents with DI were completely, or to a great extent, care dependent with regard to the CDS-item Hygiene and completely care dependent with reference to the CDS-item Dress/Undress. In comparison, hospitalized DI patients were completely, or to a great extent, care dependent with regard to the CDS-item Hygiene. CONCLUSIONS: The results of this study show that independently associated factors for incontinence also influence each other. Furthermore, these interactions increase the prevalence for incontinence and differ with regard to the type of incontinence and setting. PMID- 27196686 TI - Nocturnal Enuresis in Older People: Where Is the Evidence and What Are the Gaps? AB - While there is extensive literature regarding nocturnal enuresis in children and young adults, relatively little research explores this problem in older people. This scoping review sought to identify knowledge gaps and provide research direction specifically for older, institutionalized adults with nocturnal enuresis. A comprehensive search of 8 electronic databases and the gray literature was undertaken. Studies focusing on the causes, symptoms, and treatment of nocturnal enuresis in older people were retrieved. A broad search strategy including all adults was employed in order to capture all relevant publications. Articles were then excluded by title and abstract such that only those relevant to the older adult and institutionalized populations remained. Relevant articles were identified by title and language. Further reading of the abstract allowed inclusion and a final full reading of the articles allowed all authors to map research activity and identify knowledge gaps. After duplicates and nonrelevant articles were eliminated, we identified 7 articles on nursing home residents and 2 involving older people living in psychiatric institutions. Published literature focused on causes and treatment with either desmopressin or aversive behavioral therapy. No study included a comprehensive continence assessment or controlled for comorbid conditions. Identified gray literature focused on general continence information for the public and nonspecialist clinicians. We conclude that there is a dearth of evidence relevant to this troublesome condition. Gaps in the evidence base include a lack of standardized terminology and limited research focusing on the epidemiology, pathophysiology, and treatment of nocturnal enuresis, all of which suggest a rich research agenda for future investigation. PMID- 27196687 TI - Quality of Life After Ostomy Surgery in Muslim Patients: A Systematic Review of the Literature and Suggestions for Clinical Practice. AB - PURPOSE: To determine factors that influence health-related quality of life (HRQOL) after ostomy surgery in Muslim patients. METHODS: A systematic literature review of published data was carried out using MeSH terms ("Muslim" OR "Islam") AND ("stoma" OR "ostomy" OR "colostomy" OR "ileostomy") AND "quality of life" AND "outcomes." RESULTS: Twelve studies enrolling 913 subjects were deemed suitable for inclusion in the review. HRQOL was found to be particularly impaired in Muslims; this impairment went beyond that experienced by non-Muslim patients. Factors associated with this difference included psychological factors, social isolation, underreporting of complications, and sexual dysfunction leading to breakdown of marital relations as well as diminished religious practices. CONCLUSION: Muslims requiring ostomies should receive preoperative counseling by surgeons and ostomy nurses. These discussions should also include faith leaders and/or hospital chaplains. Ongoing support after surgery can be extended into the community and encompass family doctors and faith leaders. Additional research exploring HRQOL after surgery in Muslims living in Western societies is indicated. PMID- 27196688 TI - The Effect of Colostomy and Ileostomy on Acts of Worship in the Islamic Faith. AB - PURPOSE: The aim of this study was to determine the impact of colostomy and ileostomy on Muslim patients' acts of worship. DESIGN: This was a cross sectional, descriptive study. SUBJECTS AND SETTING: The research setting was a stoma therapy unit of a 500-bed capacity training and research hospital in Ankara, Turkey. The study sample comprised 150 patients with colostomies (40.7%) or ileostomies (59.3%); their mean age was 51.6 +/- 12.9 (mean +/- standard deviation), more than half (60.7%) were men, and 84.7% were married. METHODS: Participants were queried about specific religious practices following ostomy surgery including those related to salat, fasting, and pilgrimage. Data were collected using forms specifically designed for this study; respondents were interviewed either face-to-face or via telephone. Descriptive statistics were used to characterize the influence of a fecal ostomy on specific religious activities. RESULTS: Participants reported decreasing the frequency of daily and Friday prayers (25.2% and 22.7%, respectively) or stopped practicing these activities all together (12.0% and 14.0%, respectively). Respondents tended to increase the frequency of acts of absolution while reducing acts of fasting. Perceptions of cleanliness, central to performance of salat within the Islamic faith, emerged as a central concern. CONCLUSIONS: Ostomy surgery influences multiple religious acts practiced by Muslims. Awareness of the potential impact of a fecal ostomy on religious acts within the Islamic faith, combined with specialized education about spiritual practices delivered by the WOC nurse or a knowledgeable resource person, is strongly recommended for all persons following ostomy surgery. PMID- 27196689 TI - Investigating the accuracy of a novel telehealth diagnostic approach for autism spectrum disorder. AB - Research indicates that a substantial amount of time elapses between parents' first concerns about their child's development and a formal diagnosis of autism spectrum disorder (ASD). Telehealth presents an opportunity to expedite the diagnostic process. This project compared a novel telehealth diagnostic approach that utilizes clinically guided in-home video recordings to the gold standard in person diagnostic assessment. Participants included 40 families seeking an ASD evaluation for their child and 11 families of typically developing children. Children were between the ages of 18 months and 6 years 11 months; mean adaptive behavior composite = 75.47 (SD = 15.94). All parent participants spoke English fluently. Families completed the Naturalistic Observation Diagnostic Assessment (NODA) for ASD, which was compared to an in-person assessment (IPA). Agreement between the 2 methods, as well as sensitivity, specificity, and interrater reliability, were calculated for the full sample and the subsample of families seeking an ASD evaluation. Diagnostic agreement between NODA and the IPA was 88.2% (kappa = 0.75) in the full sample and 85% (kappa = 0.58) in the subsample. Sensitivity was 84.9% in both, whereas specificity was 94.4% in the full sample and 85.7% in the subsample. Kappa coefficients for interrater reliability indicated 85% to 90% accuracy between raters. NODA utilizes telehealth technology for families to share information with professionals and provides a method to inform clinical judgment for a diagnosis of ASD. Due to the high level of agreement with the IPA in this sample, NODA has potential to improve the efficiency of the diagnostic process for ASD. (PsycINFO Database Record PMID- 27196691 TI - Hybrid two-dimensional materials in rechargeable battery applications and their microscopic mechanisms. AB - Integration of two-dimensional (2D) nanomaterials and their composites into energy storage devices, especially rechargeable batteries, offers opportunities to timely tackle the challenges of ever growing clean and sustainable energy demands. Therefore, it is crucial to design hybrid 2D electrode materials for high performance rechargeable batteries and to fundamentally understand their storage mechanisms at the atomic or nanoscopic levels. This review firstly describes some of the exciting progress achieved in the economic production of graphenes, 2D transition metal dichalcogenides (TMDCs), and their composites. Then we survey the recent developments in their electrochemical energy storage pathways and present the associated three kinds of storage mechanisms. In addition, we highlight the uncovered structure-performance relationships while utilizing advanced microscopic techniques, such as in situ high resolution transmission electron microscopy (TEM) and spherical aberration-corrected scanning TEM (STEM), both leading to deep unveiling and understanding of the atomic-scale ion storage/release mechanisms and hence providing clear guidance for designing optimized 2D nanostructured electrode materials. Finally, the major challenges and opportunities that researchers have to face in this field are outlined. We hope that this review can deepen the Chemical and Material Science Communities' understanding of this field and thus effectively contribute to the smart design of future-generation 2D nanostructured electrodes and exploitation of their microscopic mechanisms toward novel high-performance rechargeable batteries. PMID- 27196690 TI - Psychometric analysis and validity of the daily alcohol-related consequences and evaluations measure for young adults. AB - College students experience a variety of effects resulting from alcohol use and evaluate their experiences on a continuum from negative to positive. Using daily reports collected via cell phone, we examined the psychometric properties of alcohol use consequences and evaluations of those consequences. Participants were 349 undergraduate students (mean age 19.7 [SD = 1.26], 53.4% female). Data were analyzed using a multilevel factor analysis framework, incorporating binary items (consequences) and normally distributed items (evaluations). Our model converged on 2 factors-positive and negative-with similar loadings between- and within persons. Intraclass correlation coefficients for positive consequences and their evaluations ranged from .30 to .40, whereas values for negative consequences were more variable. Intraclass correlation coefficients for negative evaluations were higher, suggesting evaluations were more trait-like compared to experience of consequences which may be context dependent. Generalizability coefficients on the whole were good to excellent, suggesting highly reliable scales at both person mean and daily-mean levels. However, likely due to binary scale and infrequency, the generalizability coefficients for negative consequences at the daily level was somewhat low. Convergent validity was demonstrated by (a) positive associations between baseline Rutgers Alcohol Problem Index and Alcohol Use Disorders Identification Test scores with latent factors for daily positive and negative consequences, and (b) positive associations between daily drinking and daily consequences and evaluations of consequences. Overall, this measure demonstrated good psychometric properties for use in studies examining daily and lagged relationships between alcohol use and related consequences. (PsycINFO Database Record PMID- 27196692 TI - Lymph Nodes and Lymphadenopathy in Cancer. PMID- 27196693 TI - Effect of Prophylactic Extended-Infusion Carboplatin on Incidence of Hypersensitivity Reactions in Patients with Ovarian, Fallopian Tube, or Peritoneal Carcinomas. AB - STUDY OBJECTIVE: To determine whether extended-infusion carboplatin, initiated at approximately the eighth cumulative carboplatin cycle and prior to development of carboplatin hypersensitivity, reduces the incidence of carboplatin hypersensitivity reactions in patients with ovarian, fallopian tube, or peritoneal cancer. DESIGN: Retrospective chart review. SETTING: Large integrated health system. PATIENTS: A total of 326 patients with ovarian, fallopian tube, or primary peritoneal cancer who received at least eight cumulative cycles of carboplatin between January 2007 and September 2014 were included. Of these, 161 patients received all doses of carboplatin infused over 30 or 60 minutes (standard-infusion group [total of 1317 carboplatin cycles]), and 165 patients received the 3-hour extended infusion of carboplatin administered at approximately the eighth cumulative cycle and prior to development of a hypersensitivity reaction (extended-infusion group [total of 1527 carboplatin cycles]). MEASUREMENTS AND MAIN RESULTS: Baseline characteristics were similar between the groups, except significantly more patients in the extended-infusion group received triple premedication therapy prior to infusion (p<0.001). Hypersensitivity reactions occurred in 64 patients (40%) who received standard infusion carboplatin and 40 patients (24.2%) who received extended-infusion carboplatin (p=0.0027). The median cycle of hypersensitivity reaction development did not differ significantly between the groups: 9 cycles in patients who received standard-infusion versus 11 cycles in patients who received extended infusion carboplatin (p=0.06). Through regression analysis, the premedication regimen received prior to carboplatin infusion was the only variable significantly associated with hypersensitivity reactions (odds ratio 0.59, 95% confidence interval 0.36-0.97, p=0.038). CONCLUSION: Patients who received extended-infusion carboplatin experienced a lower incidence of hypersensitivity reactions than patients who received standard-infusion carboplatin, which may be attributed to the triple premedication regimen received more frequently in patients in the extended-infusion group. PMID- 27196695 TI - Ionic Effects on VEGF G-Quadruplex Stability. AB - In a potassium solution, a modified 22-meric DNA sequence Pu22-T12T13 from a region proximal to the transcription initiation site of the human VEGF gene adopts a single parallel-stranded G-quadruplex conformation with a 1:4:1 loop size arrangement. We measured the thermal stability, TM, of the K(+)-stabilized Pu22-T12T13 G-quadruplex as a function of stabilizing K(+) ions and nonstabilizing Cs(+) and TMA(+) ions. The thermal stability, TM, of the Pu22 T12T13 G-quadruplex increases with the concentration of the stabilizing potassium ions, while it sharply decreases upon the addition of the nonstabilizing cations. We interpret these results as underscoring the opposing effects of internal binding and counterion condensation on the stability of the Pu22-T12T13 G quadruplex. While centrally bound ions stabilize the G-quadruplex conformation, counterion condensation destabilizes it, favoring the coil conformation. From the initial slopes of the dependences of TM on the concentration of Cs(+) and TMA(+) cations, we estimate that the deleterious effect of counterion condensation stems from roughly one extra counterion associated with the coil relative to the G quadruplex state of Pu22-T12T13. The reduced accumulation of counterions around the G-quadruplex state of Pu22-T12T13 relative to its coil state is due to the low surface charge density of the G-quadruplex reflecting its structural characteristics. On the basis of the analysis of our data along with the results of a previous study, we propose that the differential effect of internally (stabilizing) and externally (destabilizing) bound cations may be a general feature of parallel intramolecular G-quadruplexes. PMID- 27196694 TI - Comparison of mHTT Antibodies in Huntington's Disease Mouse Models Reveal Specific Binding Profiles and Steady-State Ubiquitin Levels with Disease Development. AB - Huntington's disease (HD) cellular pathology is characterised by the aggregation of mutant huntingtin (mHTT) protein into inclusion bodies. The present paper compared the sensitivity of five widely used mHTT antibodies (S830; MW8; EM48; 1C2; ubiquitin) against mice from five commonly used HD mouse models (R6/1; YAC128; HdhQ92; B6 HdhQ150; B6 x129/Ola HdhQ150) at two ages to determine: the most sensitive antibodies for each model; whether mHTT antibody binding differed depending on aggregation stage (diffuse versus frank inclusion); the role of ubiquitin during aggregation as the ubiquitin proteosome system has been implicated in disease development. The models demonstrated unique profiles of antibody binding even when the models varied only by background strain (HdhQ150). MW8 was highly sensitive for detecting frank inclusions in all lines whereas EM48, ubiquitin and 1C2 demonstrated consistent staining in all models irrespective of age or form of mHTT. MW8 and S830 were the most sensitive antibodies with 1C2 the least. Ubiquitin levels were stable for each model regardless of age. Ubiquitin was particularly sensitive in young YAC128 mice that demonstrate an absence of inclusions until ~12 months of age suggesting high affinity to mHTT in its diffuse form. The data indicate that generalisations across models regarding the quantification of aggregations may not be valid and that mHTT antibody binding is unique to the mouse model and sensitive to changes in inclusion development. PMID- 27196696 TI - A Single Mechanism Can Account for Human Perception of Depth in Mixed Correlation Random Dot Stereograms. AB - In order to extract retinal disparity from a visual scene, the brain must match corresponding points in the left and right retinae. This computationally demanding task is known as the stereo correspondence problem. The initial stage of the solution to the correspondence problem is generally thought to consist of a correlation-based computation. However, recent work by Doi et al suggests that human observers can see depth in a class of stimuli where the mean binocular correlation is 0 (half-matched random dot stereograms). Half-matched random dot stereograms are made up of an equal number of correlated and anticorrelated dots, and the binocular energy model-a well-known model of V1 binocular complex cells fails to signal disparity here. This has led to the proposition that a second, match-based computation must be extracting disparity in these stimuli. Here we show that a straightforward modification to the binocular energy model-adding a point output nonlinearity-is by itself sufficient to produce cells that are disparity-tuned to half-matched random dot stereograms. We then show that a simple decision model using this single mechanism can reproduce psychometric functions generated by human observers, including reduced performance to large disparities and rapidly updating dot patterns. The model makes predictions about how performance should change with dot size in half-matched stereograms and temporal alternation in correlation, which we test in human observers. We conclude that a single correlation-based computation, based directly on already known properties of V1 neurons, can account for the literature on mixed correlation random dot stereograms. PMID- 27196698 TI - A systematic analysis of methylene blue for drug-induced shock. AB - CONTEXT: Pharmacologically induced shock can be refractory to standard resuscitation. Methylene blue (MB) acts to prevent nitric oxide-mediated vasodilation and may be a potential treatment for refractory shock. OBJECTIVE: A systematic analysis of the literature to evaluate MB in pharmacologically induced shock. Primary outcome was survival and secondary outcome was hemodynamic improvement. MATERIALS AND METHODS: A search of MedLine/PubMed, EMBASE, Cochrane Library, TOXLINE, Google Scholar and Google was performed 10 August 2015 using a combination of text words and keywords related to MB, shock and specific drugs. We included primary literature articles reporting clinical outcomes in humans. RESULTS: The searches yielded 928 citations, with 255 exact duplicates. Of the 673 entries screened, 16 citations met study criteria and comprised 17 cases. Calcium channel blockers (CCBs) represented ten cases (six amlodipine, two verapamil, and two diltiazem), atenolol three cases as coingestant with amlodipine, five metformin, one ibuprofen, and one multidrug (quetiapine, carbamazepine, valproic acid, oxazepam, and fluoxetine). Twelve patients survived and nine had hemodynamic improvement following MB administration. Four did not respond to MB but survived with other advanced resuscitative measures. None of the seven cases had BP improvement and four died when lipid was given prior to MB, compared to one death and nine cases of BP improvement when lipid was not given. In all cases, MB was used after failing several other treatments. Bolus doses ranging from 1 to 3 mg/kg, with repeat boluses or maintenance infusions. Reported adverse events were temporary self-limited blue discolorations. CONCLUSION: While there are compelling cases describing an improved hemodynamic status following MB, there are also several cases without observed change. Currently, there is not enough evidence available to recommend the routine administration of MB in refractory pharmacologically induced shock. PMID- 27196697 TI - FKBP5 genotype interacts with early life trauma to predict heavy drinking in college students. AB - Alcohol use disorder (AUD) is debilitating and costly. Identification and better understanding of risk factors influencing the development of AUD remain a research priority. Although early life exposure to trauma increases the risk of adulthood psychiatric disorders, including AUD, many individuals exposed to early life trauma do not develop psychopathology. Underlying genetic factors may contribute to differential sensitivity to trauma experienced in childhood. The hypothalamic-pituitary-adrenal (HPA) axis is susceptible to long-lasting changes in function following childhood trauma. Functional genetic variation within FKBP5, a gene encoding a modulator of HPA axis function, is associated with the development of psychiatric symptoms in adulthood, particularly among individuals exposed to trauma early in life. In the current study, we examined interactions between self-reported early life trauma, past-year life stress, past-year trauma, and a single nucleotide polymorphism (rs1360780) in FKBP5 on heavy alcohol consumption in a sample of 1,845 college students from two university settings. Although we found no effect of early life trauma on heavy drinking in rs1360780*T allele carriers, rs1360780*C homozygotes exposed to early life trauma had a lower probability of heavy drinking compared to rs1360780*C homozygotes not exposed to early life trauma (P < 0.01). The absence of an interaction between either current life stress or past-year trauma, and FKBP5 genotype on heavy drinking suggests that there exists a developmental period of susceptibility to stress that is moderated by FKBP5 genotype. These findings implicate interactive effects of early life trauma and FKBP5 genetic variation on heavy drinking. (c) 2016 Wiley Periodicals, Inc. PMID- 27196699 TI - Effects of intimate partner violence, PTSD, and alcohol use on cigarette smoking in a nationally representative sample. AB - BACKGROUND AND OBJECTIVES: Separate literatures indicate that intimate partner violence (IPV), posttraumatic stress disorder (PTSD), and alcohol use are independently associated with increased risk for cigarette smoking. No previous studies have examined the co-occurrence of these problems on smoking quantity and potential gender-specific relationships. This study will address this gap in the literature. METHODS: Data from Wave 2 of the National Epidemiologic Study on Alcohol and Related Conditions (NESARC) were examined. Variables were assessed during the past year. Individuals (N = 25,604) who reported being married, dating, or involved in a romantic relationship were included. RESULTS: Among men, PTSD and alcohol use were associated with more cigarettes smoked per day. Among women, PTSD, alcohol use, and IPV victimization were associated with more cigarettes smoked per day. Women who experienced IPV victimization smoked approximately three additional cigarettes per day. DISCUSSION AND CONCLUSIONS: IPV victimization, PTSD, and alcohol use were associated with cigarettes smoked among women, while IPV experiences were not associated with smoking risk among men. SCIENTIFIC SIGNIFICANCE: These findings represent an important contribution to the existing literature in that it elucidates the compounding relationship between a common and complex comorbidity and cigarette smoking. Findings indicate a critical need to implement routine smoking screening and intervention in venues where intimate partner violence is commonly encountered, such as advocacy and substance use treatment settings. (Am J Addict 2016;25:283-290). PMID- 27196700 TI - Geographical Area and Life History Traits Influence Diet in an Arctic Marine Predator. AB - Global changes are thought to affect most Arctic species, yet some populations are more at risk. Today, the Barents Sea ecoregion is suffering the strongest sea ice retreat ever measured; and these changes are suspected to modify food access and thus diet of several species. Biochemical diet tracers enable investigation of diet in species such as polar bears (Ursus maritimus). We examined individual diet variation of female polar bears in Svalbard, Norway, and related it to year, season (spring and autumn), sampling area and breeding status (solitary, with cubs of the year or yearlings). Sampling areas were split according to their ice cover: North-West (less sea ice cover), South-East (larger amplitude in sea ice extent) and North-East/South-West (NESW) as bears from that zone are more mobile among all regions of Svalbard. We measured fatty acid (FA) composition in adipose tissue and carbon (delta13C) and nitrogen (delta15N) stable isotopes in plasma and red blood cells. Females feeding in the North-West area had lower delta15N values than those from the NESW. In South-East females, delta13C values were lower in autumn compared to spring and females seemed less selective in their diet as depicted by large variances in stable isotope values. Considering the differences in FA composition and stable isotope values, we suggest that females from the North-West and South-East could ingest a higher proportion of avian prey. With regard to breeding status, solitary females had higher delta15N values and smaller variance in their stable isotopic values than females with cubs, suggesting that solitary females were more selective and prey on higher trophic level species (i.e. seals). Overall, our results indicate that prey availability for Svalbard polar bears varies according to geographical area and prey selectivity differs according to breeding status. Our findings suggest that complex changes in sea ice and prey availability will interact to affect Svalbard polar bear feeding patterns and associated nutrition. PMID- 27196701 TI - Guidelines for the management of diffuse large B-cell lymphoma. PMID- 27196702 TI - One-step gene delivery into the cytoplasm in a fusion-dependent manner based on a new membrane fusogenic lipid. AB - A new type of membrane fusogenic lipid was prepared to deliver DNA or siRNA into the cytoplasm directly in a fusion-dependent manner in order to bypass the cellular endocytosis to avoid the inefficient escape from the endosome and low transfection efficacy. PMID- 27196704 TI - Dispersion and shear-induced orientation of anisotropic nanoparticle filled polymer nanocomposites: insights from molecular dynamics simulation. AB - Although a large number of studies have been performed to study the dispersion behavior of spherical nanoparticles (NPs) in the polymer matrix, little effort has been directed to anisotropic NPs via simulation, which is convenient for controlling the physical parameters compared to experiment. In this work we adopt molecular dynamics simulation to study polymer nanocomposites filled with anisotropic NPs such as graphene and carbon nanotubes (CNTs). We investigate the effects of the grafting position, grafting density, the length and flexibility of the grafted chains on the dispersion of graphene and CNTs. In particular, we find that when the grafting position is located on the surface center of the graphene or the middle of the CNT, the dispersion state is the best, leading to the greatest stress-strain behavior. Meanwhile, the mechanical property can be further strengthened by introducing chemical couplings in the interfacial region, by chemically tethering the grafted chains to the matrix chains. To monitor the processing effect, we exert a dynamic periodic shear deformation in the x direction with its gradient in the y direction. Polymer chains are found to align in the x direction, graphene sheets align in the xoz plane and CNTs orientate in the z direction. We study the effects of the shear amplitude, the shear frequency, polymer-NP interaction strength and volume fraction of NPs on the stress-strain behavior. We also observe that the relaxation process following the shear deformation deteriorates the mechanical performance, resulting from the disorientation of polymer chains and NPs. In general, this work could provide valuable guidance in manipulating the distribution and alignment of graphene and CNTs in the polymer matrix. PMID- 27196703 TI - Regulation of melanocortin 1 receptor in allergic rhinitis in vitro and in vivo. AB - BACKGROUND: alpha-melanocyte-stimulating hormone (alpha-MSH) was shown to inhibit allergic airway inflammation and exert suppressive effects on human basophils. OBJECTIVE: This study aims to extend our current knowledge on the melanocortin 1 receptor (MC1R) expression in nasal tissue of patients with allergic rhinitis (AR) and functional effects of alpha-MSH in human basophils especially from patients with allergic rhinitis. METHODS: MC1R expression before and after nasal allergen provocation was studied in nasal mucosal tissue of AR patients and in a mouse model of allergic airway inflammation using immunofluorescence. In vitro regulation of the MC1R and CD203c surface expression on whole-blood basophils of patients with AR and controls was assessed with flow cytometry. Functional effects of alpha-MSH on isolated basophils were analysed regarding apoptosis with flow cytometry and chemotaxis using a Boyden chamber assay. RESULTS: We detected an accumulation of MC1R-positive basophils in nasal mucosa tissue of patients with AR 24 h after nasal allergen provocation. Such accumulation was not present in mucosa sections from healthy controls. In mice with allergic airway inflammation, we found a clear accumulation of MC1R-positive basophils in the nasal tissue compared to control mice. MC1R expression was inducible in AR patients and controls by stimulation with anti-IgE. alpha-MSH inhibited anti-IgE and grass pollen induced upregulation of CD203c, but had no effect on chemotaxis or apoptosis of basophils in vitro. CONCLUSIONS AND CLINICAL RELEVANCE: MC1R positive basophils accumulate in the nasal mucosa of patients with AR after nasal allergen provocation. Since alpha-MSH suppresses proinflammatory effector functions in human basophils via the MC1R, it constitutes an interesting novel target for modulating the allergic inflammatory response. PMID- 27196705 TI - Zoledronic acid in vivo increases in vitro proliferation of rat mesenchymal stromal cells. AB - Background and purpose - Bisphosphonates are widely used in the treatment of bone loss, but they might also have positive effects on osteoblastic cells and bone formation. We evaluated the effect of in vivo zoledronic acid (ZA) treatment and possible concomitant effects of ZA and fracture on the ex vivo osteogenic capacity of rat mesenchymal stromal cells (MSCs). Methods - A closed femoral fracture model was used in adult female rats and ZA was administered as a single bolus or as weekly doses up to 8 weeks. Bone marrow MSCs were isolated and cultured for in vitro analyses. Fracture healing was evaluated by radiography, micro-computed tomography (MUCT), and histology. Results - Both bolus and weekly ZA increased fracture-site bone mineral content and volume. MSCs from weekly ZA treated animals showed increased ex vivo proliferative capacity, while no substantial effect on osteoblastic differentiation was observed. Fracture itself did not have any substantial effect on cell proliferation or differentiation at 8 weeks. Serum biochemical markers showed higher levels of bone formation in animals with fracture than in intact animals, while no difference in bone resorption was observed. Interestingly, ex vivo osteoblastic differentiation of MSCs was found to correlate with in vivo serum bone markers. Interpretation - Our data show that in vivo zoledronic acid treatment can influence ex vivo proliferation of MSCs, indicating that bisphosphonates can have sustainable effects on cells of the osteoblastic lineage. Further research is needed to investigate the mechanisms. PMID- 27196706 TI - Atrial fibrillation burden and atrial fibrillation type: Clinical significance and impact on the risk of stroke and decision making for long-term anticoagulation. AB - Atrial fibrillation (AF) is a common arrhythmia increasing the risk of morbidity and adverse outcomes (stroke, heart failure, death). AF is found in 1-2% of the general population, with increasing prevalence with aging. Its exact epidemiological profile is incomplete and underestimated, because 10-40% of AF patients (particularly the elderly) can be asymptomatic ("clinically silent or subclinical AF"), with occasional electrocardiographic diagnosis. The research interest on silent AF has increased by the evidence that its outcome is no less severe, in terms of risks of stroke and death, than that for symptomatic patients. Data collected from more than 18,000 patients indicate that cardiac implantable electrical devices (CIEDs) are validated tools for detecting silent AF and measuring the time spent in AF, defined as "AF burden." A maximum daily AF burden of >=5-6min, but particularly >=1h, is associated with a significant increase in the risk of stroke, and may be clinically relevant to improve current risk stratification based on risk scores and for "personalizing" prescription of oral anticoagulants. An in-depth study of the temporal relationship between AF and ischemic stroke showed that data from CIEDs reveal a complex scenario, by which AF is certainly a risk factor for cardioembolic stroke, with a cause-effect relationship related to atrial thrombi, but can also be a simple "marker of risk," with a noncausal association with stroke. In such cases, stroke is possibly related to atheroemboli from the aorta, the carotid arteries, or other sources. PMID- 27196716 TI - Synthesis and characterization of smart N-isopropylacrylamide-based magnetic nanocomposites containing doxorubicin anti-cancer drug. AB - In the present study, magnetic and thermo/pH-sensitive (multiresponsive) nanocomposites based on N-isopropylacrylamide (NIPAAM) were synthesized and characterized. Nanocomposites were synthesized by free radical emulsion polymerization of NIPAAM as thermosensitive monomer and N,N-dimethyl-aminoethyl methacrylate (DMAEMA) as pH-sensitive monomer in the presence of methylene-bis acrylamide as cross-linking agent. Doxorubicin, an anti-cancer drug, was loaded into these nanocomposites via equilibrium swelling method. Thermo/pH-sensitive cross-linked poly (NIPAAM-DMAEMA)-Fe3O4 nanocomposites were characterized by Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and vibrating sample magnetometer (VSM). The volume of the loaded drug and drug release amount was determined by UV measurements. The results showed that this thermo/pH-sensitive magnetic nanocomposite has a high drug-loading efficiency. Doxorubicin was released at 40 degrees C and pH 5.8 more than the 37 degrees C and pH 7.4. PMID- 27196715 TI - The effects of injection modes on instantaneous particle deposition in a realistic human nasal cavity. AB - To understand the instantaneous particle deposition in nasal cavity, effects of two injection models on particle deposition characteristic were discussed in this paper. Based on a realistic human nasal cavity geometry obtained from CT scans, a comparison of deposition pattern in the nasal cavity between single injection and continuous injection was investigated through the Lagrangian approach. The instantaneous airflow field was simulated with the tidal volume of 159 and 318 mL by two sine wave curves at inlet. For the case of single injection, particles have finished deposition in the first half of inhalation, and a negative correlation between the tidal volumes and deposition can be observed when the particle diameter was larger than 10 um. Moreover, particles were mainly deposited in the turbinate area that was beneficial for aerosol therapy. The inertial parameter was not suitable to predict the particle deposition in the case of single injection. With respect to continuous injection, a reduction in total deposition caused by the deceleration process of inhalation can be observed after 1.5 s. The deposition was closely associated with the time-varying flow field, and particles were mainly deposited in the anterior region and turbinate area. Besides, the particle deposition increased with the inertial parameter for continuous injection. The results indicated that the injection modes had an influence on both the total deposition and local deposition pattern in the nasal cavity. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27196718 TI - Announcement: Healthy and Safe Swimming Week - May 23-29, 2016. AB - May 23-29, 2016, marks the 12th annual Healthy and Safe Swimming Week.* This observance highlights ways that swimmers; parents of young swimmers; aquatic facility operators; residential pool, hot tub, or spa owners; beach managers; and public health officials can maximize the health benefits of water-based physical activity while minimizing the risk for recreational water-associated illness and injury. PMID- 27196717 TI - Affinity capillary electrophoresis in studying the complex formation equilibria of radionuclides in aqueous solutions. AB - Interaction of radionuclides with inorganic and organic species present in natural environment plays an important role in their eventual dispersion. The complex equilibria established in the aqueous phase cause significant changes in the migration properties of radionuclides. Affinity capillary electrophoresis (ACE) can be fruitful in studying these equilibria. This paper reviews the recent methodological advances of the use of ACE in studying the complex equilibria of radionuclides in aqueous solutions. Special attention is paid to the determination of a number of species involved in equilibrium, species constituents (number of ligands, protonated, deprotonated), the influence of ionic strength and temperature on stability constants of complex species formed. Use of ACE for the determination of the main thermodynamic parameters (the molar Gibbs energy (Deltar Gm ), the molar enthalpy (Deltar Hm ) and the molar entropy (Deltar Sm )) of complex formation reactions is also discussed. These data are essential to predict dispersion of radionuclides in the natural environment. PMID- 27196721 TI - Controlling Au Photodeposition on Large ZnO Nanoparticles. AB - This study investigated how to control the rate of photoreduction of metastable AuCl2(-) at the solid-solution interface of large ZnO nanoparticles (NPs) (50-100 nm size). Band-gap photoexcitation of electronic charge in ZnO by 370 nm UV light yielded Au NP deposition and the formation of ZnO-Au NP hybrids. Au NP growth was observed to be nonepitaxial, and the patterns of Au photodeposition onto ZnO NPs observed by high-resolution transmission electron microscopy were consistent with reduction of AuCl2(-) at ZnO facet edges and corner sites. Au NP photodeposition was effective in the presence of labile oleylamine ligands attached to the ZnO surface; however, when a strong-binding dodecanethiol ligand coated the surface, photodeposition was quenched. Rates of interfacial electron transfer at the ZnO solution interface were adjusted by changing the solvent, and these rates were observed to strongly depend on the solvent's permittivity (epsilon) and viscosity. From measurements of electron transfer from ZnO to the organic dye toluidine blue at the ZnO-solution interface, it was confirmed that low epsilon solvent mixtures (epsilon ~ 9.5) possessed markedly higher rates of photocatalytic interfacial electron transfer (~3.2 * 10(4) electrons.particle( 1).s(-1)) compared to solvent mixtures with high epsilon (epsilon = 29.9, ~1.9 * 10(4) electrons.particle(-1).s(-1)). Dissolved oxygen content in the solvent and the exposure time of ZnO to band-gap, near-UV photoexcitation were also identified as factors that strongly affected Au photodeposition behavior. Production of Au clusters was favored under conditions that caused electron accumulation in the ZnO-Au NP hybrid. Under conditions where electron discharge was rapid (such as in low epsilon solvents), AuCl2(-) precursor ions photoreduced at ZnO surfaces in less than 5 s, leading to deposition of several small, isolated ~6 nm Au NP on the ZnO host instead. PMID- 27196723 TI - Analysis of longitudinal data from animals with missing values using SPSS. AB - Testing of therapies for disease or injury often involves the analysis of longitudinal data from animals. Modern analytical methods have advantages over conventional methods (particularly when some data are missing), yet they are not used widely by preclinical researchers. Here we provide an easy-to-use protocol for the analysis of longitudinal data from animals, and we present a click-by click guide for performing suitable analyses using the statistical package IBM SPSS Statistics software (SPSS). We guide readers through the analysis of a real life data set obtained when testing a therapy for brain injury (stroke) in elderly rats. If a few data points are missing, as in this example data set (for example, because of animal dropout), repeated-measures analysis of covariance may fail to detect a treatment effect. An alternative analysis method, such as the use of linear models (with various covariance structures), and analysis using restricted maximum likelihood estimation (to include all available data) can be used to better detect treatment effects. This protocol takes 2 h to carry out. PMID- 27196722 TI - Characterization of proteins by in-cell NMR spectroscopy in cultured mammalian cells. AB - In-cell NMR spectroscopy is a unique tool for characterizing biological macromolecules in their physiological environment at atomic resolution. Recent progress in NMR instruments and sample preparation methods allows functional processes, such as metal uptake, disulfide-bond formation and protein folding, to be analyzed by NMR in living, cultured human cells. This protocol describes the necessary steps to overexpress one or more proteins of interest inside human embryonic kidney 293T (HEK293T) cells, and it explains how to set up in-cell NMR experiments. The cDNA is transiently transfected as a complex with a cationic polymer (DNA:PEI (polyethylenimine)), and protein expression is carried on for 2 3 d, after which the NMR sample is prepared. (1)H and (1)H-(15)N correlation NMR experiments (for example, using band-selective optimized flip-angle short transient heteronuclear multiple quantum coherence (SOFAST-HMQC)) can be carried out in <2 h, ensuring cell viability. Uniform (15)N labeling and amino-acid specific (e.g., cysteine, methionine) labeling schemes are possible. The entire procedure takes 4 d from cell culture seeding to NMR data collection. PMID- 27196724 TI - Protection against 1-methyl-4-phenyl pyridinium-induced neurotoxicity in human neuroblastoma SH-SY5Y cells by Soyasaponin I by the activation of the phosphoinositide 3-kinase/AKT/GSK3beta pathway. AB - Parkinson's disease (PD) can be ascribed to the progressive and selective loss of dopaminergic neurons in the substantia nigra pars compacta, and thus molecules with neuroprotective ability may have therapeutic value against PD. In the current study, the neuroprotective effects and underlying mechanisms of Soyasaponin I (Soya-I), a naturally occurring triterpene extracted from a widely used ingredient in many foods, such as Glycine max (soybean), were evaluated in a widely used cellular PD model in which neurotoxicity was induced by 1-methyl-4 phenyl pyridinium (MPP) in cultured SH-SY5Y cells. We found that Soya-I at 10-40 MUM considerably protected against MPP-induced neurotoxicity as evidenced by an increase in cell viability, a decrease in lactate dehydrogenase release, and a reduction in apoptotic nuclei. Moreover, Soya-I effectively inhibited the elevated intracellular accumulation of reactive oxygen species as well as the Bax/Bcl-2 ratio caused by MPP. Most importantly, Soya-I markedly reversed the inhibition of protein expression of phosphorylated AKT and phosphorylated GSK3beta caused by MPP. LY294002, the specific inhibitor of phosphoinositide 3 kinase, significantly abrogated the upregulated phosphorylated AKT and phosphorylated GSK3beta offered by Soya-I, suggesting that the neuroprotection of Soya-I was mainly dependent on the activation of the phosphoinositide 3 kinase/AKT/GSK3beta signaling pathway. The results taken together indicate that Soya-I may be a potential candidate for further preclinical study aimed at the prevention and treatment of PD. PMID- 27196725 TI - Temporal cognition: Connecting subjective time to perception, attention, and memory. AB - Time is a universal psychological dimension, but time perception has often been studied and discussed in relative isolation. Increasingly, researchers are searching for unifying principles and integrated models that link time perception to other domains. In this review, we survey the links between temporal cognition and other psychological processes. Specifically, we describe how subjective duration is affected by nontemporal stimulus properties (perception), the allocation of processing resources (attention), and past experience with the stimulus (memory). We show that many of these connections instantiate a "processing principle," according to which perceived time is positively related to perceptual vividity and the ease of extracting information from the stimulus. This empirical generalization generates testable predictions and provides a starting-point for integrated theoretical frameworks. By outlining some of the links between temporal cognition and other domains, and by providing a unifying principle for understanding these effects, we hope to encourage time-perception researchers to situate their work within broader theoretical frameworks, and that researchers from other fields will be inspired to apply their insights, techniques, and theorizing to improve our understanding of the representation and judgment of time. (PsycINFO Database Record PMID- 27196726 TI - Management of Retinal Whitening With Vitritis. PMID- 27196729 TI - Monochloramine Cometabolism by Mixed-Culture Nitrifiers under Drinking Water Conditions. AB - Chloramines are the second most used secondary disinfectant by United States water utilities. However, chloramination may promote nitrifying bacteria. Recently, monochloramine cometabolism by the pure culture ammonia-oxidizing bacteria, Nitrosomonas europaea, was shown to increase monochloramine demand. The current research investigated monochloramine cometabolism by nitrifying mixed cultures grown under more relevant drinking water conditions and harvested from sand-packed reactors before conducting suspended growth batch kinetic experiments. Four types of batch kinetic experiments were conducted: (1) positive controls to estimate ammonia kinetic parameters, (2) negative controls to account for biomass reactivity, (3) utilization associated product (UAP) controls to account for UAP reactivity, and (4) cometabolism experiments to estimate cometabolism kinetic parameters. Kinetic parameters were estimated in AQUASIM with a simultaneous fit to the experimental data. Cometabolism kinetics were best described by a first-order model. Monochloramine cometabolism kinetics were similar to those of ammonia metabolism, and monochloramine cometabolism accounted for 30% of the observed monochloramine loss. These results demonstrated that monochloramine cometabolism occurred in mixed cultures similar to those found in drinking water distribution systems; therefore, monochloramine cometabolism may be a significant contribution to monochloramine loss during nitrification episodes in drinking water distribution systems. PMID- 27196728 TI - Dendritic Cell-Like Cells Accumulate in Regenerating Murine Skeletal Muscle after Injury and Boost Adaptive Immune Responses Only upon a Microbial Challenge. AB - Skeletal muscle injury causes a local sterile inflammatory response. In parallel, a state of immunosuppression develops distal to the site of tissue damage. Granulocytes and monocytes that are rapidly recruited to the site of injury contribute to tissue regeneration. In this study we used a mouse model of traumatic skeletal muscle injury to investigate the previously unknown role of dendritic cells (DCs) that accumulate in injured tissue. We injected the model antigen ovalbumin (OVA) into the skeletal muscle of injured or sham-treated mice to address the ability of these DCs in antigen uptake, migration, and specific T cell activation in the draining popliteal lymph node (pLN). Immature DC-like cells appeared in the skeletal muscle by 4 days after injury and subsequently acquired a mature phenotype, as indicated by increased expression of the costimulatory molecules CD40 and CD86. After the injection of OVA into the muscle, OVA-loaded DCs migrated into the pLN. The migration of DC-like cells from the injured muscle was enhanced in the presence of the microbial stimulus lipopolysaccharide at the site of antigen uptake and triggered an increased OVA specific T helper cell type 1 (Th1) response in the pLN. Naive OVA-loaded DCs were superior in Th1-like priming in the pLN when adoptively transferred into the skeletal muscle of injured mice, a finding indicating the relevance of the microenvironment in the regenerating skeletal muscle for increased Th1-like priming. These findings suggest that DC-like cells that accumulate in the regenerating muscle initiate a protective immune response upon microbial challenge and thereby overcome injury-induced immunosuppression. PMID- 27196730 TI - Stomatal Dimorphism of Neodiplogaster acaloleptae (Diplogastromorpha: Diplogastridae). AB - Several genera belonging to the nematode family Diplogastridae show characteristic dimorphism in their feeding structures; specifically, they have microbial feeding stenostomatous and predatory eurystomatous morphs. A diplogastrid satellite model species, Pristionchus pacificus, and its close relatives have become a model system for studying this phenotypic plasticity, with intensive physiological and structural studies having been undertaken. However, the many other species that are morphologically and phylogenetically divergent from P. pacificus have not been examined to date. In the present study, the detailed stomatal structure and induction of dimorphism in Neodiplogaster acaloleptae were examined. N. acaloleptae has a fungal feeding stenostomatous morph and a predatory eurystomatous morph. The predatory morph was induced by starvation, high population density, and co-culturing with its potential prey, Caenorhabditis elegans. The feeding behavior of the stenostomatous and eurystomatous morphs of N. acaloleptae was confirmed, demonstrating that 1) the stomatal and pharyngeal movements of the two morphs were basically identical, and 2) the stomatal elements were protracted to cut open the hyphae and/or prey to feed when a N. acaloleptae flips its dorsal movable tooth dorsally and tilts its subventral stegostomatal cylinder ventrally, forming a pair of scissors to cut the food source. The stoma morphology of N. acaloleptae with a single movable tooth and a long stoma is markedly different from that of Pristionchus, which has two movable teeth and a short stoma. It is, however, similar to that of Mononchoides, tentatively a sister to Neodiplogaster. PMID- 27196731 TI - Implant-Supported Immediately Loaded Fixed Full-Arch Dentures: Evaluation of Implant Survival Rates in a Case Cohort of up to 7 Years. AB - BACKGROUND: The treatment of severely atrophied and edentulous jaws by means of fixed implant supported solutions is a challenging procedure. PURPOSE: The immediate loading of four to six axial and tilted implants offers the possibility to overcome elaborate hard tissue augmentation procedures but lacks implant and patient related data on implant survival rates. MATERIALS AND METHODS: This retrospective 7-years clinical trial investigated the implant survival rates of 2,081 implants (380 patients, 482 jaws) using an immediate loading protocol with either 4, 5, or 6 implants per restoration. Survival rates were calculated concerning implantation related factors (jaws/number of supporting implants/angulations/diameters/lengths) and patient related factors (medical status/smoking). RESULTS: Overall survival of 2,081 implants was 97.0% on implant level. Survival rates of implantation related factors did not yield significant differences. Significant differences were yield between healthy patients and patients with osteoporosis (p = .002) and the medical status group "other" (p = .032), respectively. Smokers yielded a significantly higher survival than nonsmokers (p = .002). CONCLUSIONS: It is assumed that four implants per jaw serve as a sufficient implant number for full arch restorations in both, the mandible and the maxilla. Osteoporosis under the medication with bisphosphonates seems to be a risk factor for implant survival. The authors suggest that the effect of smoking on ISRs remains controversial within this treatment concept. PMID- 27196732 TI - Development of human monoclonal antibodies to diphtheria toxin: A solution for the increasing lack of equine DAT for therapeutic use? PMID- 27196733 TI - Molybdate uptake by Agrobacterium tumefaciens correlates with the cellular molybdenum cofactor status. AB - Many enzymes require the molybdenum cofactor, Moco. Under Mo-limiting conditions, the high-affinity ABC transporter ModABC permits molybdate uptake and Moco biosynthesis in bacteria. Under Mo-replete conditions, Escherichia coli represses modABC transcription by the one-component regulator, ModE, consisting of a DNA binding and a molybdate-sensing domain. Instead of a full-length ModE protein, many bacteria have a shorter ModE protein, ModE(S) , consisting of a DNA-binding domain only. Here, we asked how such proteins sense the intracellular molybdenum status. We show that the Agrobacterium tumefaciens ModE(S) protein Atu2564 is essential for modABC repression. ModE(S) binds two Mo-boxes in the modA promoter as shown by electrophoretic mobility shift assays. Northern analysis revealed cotranscription of modE(S) with the upstream gene, atu2565, which was dispensable for ModE(S) activity. To identify genes controlling ModE(S) function, we performed transposon mutagenesis. Tn5 insertions resulting in derepressed modA transcription mapped to the atu2565-modE(S) operon and several Moco biosynthesis genes. We conclude that A. tumefaciens ModE(S) activity responds to Moco availability rather than to molybdate concentration directly, as is the case for E. coli ModE. Similar results in Sinorhizobium meliloti suggest that Moco dependence is a common feature of ModE(S) regulators. PMID- 27196734 TI - Observations on failed retrieval of optional inferior vena cava filters. AB - PURPOSE: To evaluate causes of failed optional inferior vena cava filter (IVCF) retrievals. METHODS: Single-center retrospective study. RESULTS: IVCF retrievals were attempted in 26/211 (12%) patients at a mean 42.9 days. There were 9 failures (all OptEase) due to: inability to snare the hook (n=5), noncollapsible IVCF (n=3), and unusual procedural pain (n=1). Median duration of retrieved IVCFs was 31 days compared to 53 days for failures (P<.05). IVCFs aligned with the IVC's cephalocaudal axis were retrieved in 13/16 cases, while misaligned IVCFs were retrieved 4/10 cases (P<.05). CONCLUSION: Filter duration and misalignment were significantly associated with retrieval failures. PMID- 27196727 TI - Estrogens, Neuroinflammation, and Neurodegeneration. AB - Inflammatory activation of microglia is a hallmark of several disorders of the central nervous system. In addition to protecting the brain against inflammatory insults, microglia are neuroprotective and play a significant role in maintaining neuronal connectivity, but the prolongation of an inflammatory status may limit the beneficial functions of these immune cells. The finding that estrogen receptors are present in monocyte-derived cells and that estrogens prevent and control the inflammatory response raise the question of the role that this sex steroid plays in the manifestation and progression of pathologies that have a clear sex difference in prevalence, such as multiple sclerosis, Parkinson's disease, and Alzheimer's disease. The present review aims to provide a critical review of the current literature on the actions of estrogen in microglia and on the involvement of estrogen receptors in the manifestation of selected neurological disorders. This current understanding highlights a research area that should be expanded to identify appropriate replacement therapies to slow the progression of such diseases. PMID- 27196737 TI - Long-Term Outcomes after Endoscopic Treatment of Gastric Gastrointestinal Stromal Tumor. AB - Endoscopic resection of gastric subepithelial tumors (SETs) has several advantages over biopsy techniques, such as superior diagnostic yield and definite diagnosis. Removal of gastric SETs and histopathologic confirmation should be considered whenever gastric SETs are highly suspected to have malignant potential such as gastrointestinal stromal tumor (GIST) or neuroendocrine tumor. According to our clinical experience, we suggest that endoscopic resection of gastric SETs is feasible for GISTs less than 3.0 cm without positive endoscopic ultrasonography findings or for hypoechoic SETs less than 3.0 cm. However, serious complications such as macroperforation may occur during endoscopic resection, and this procedure is highly dependent on endoscopists' skills. We recently reported the long-term clinical outcomes of endoscopic resection of gastric GIST, which showed a relatively low recurrence rate (2.2%) during long term follow-up (46.0+/-28.5 months) despite the low R0 resection rate (25.0%). We suggest that endoscopic surveillance might be possible without additional surgical resection in completely resected GISTs without residual tumor confirmed to be lower risk, even if they show an R1 resection margin. PMID- 27196736 TI - Efficacy of Albis for the Prevention of Gastric Mucosal Injury Concomitant with the Use of Low-Dose Aspirin: A Prospective, Randomized, Placebo-Controlled Study. AB - BACKGROUND/AIMS: Long-term use of aspirin can be a risk factor of peptic ulcer diseases. The aim of this study was to evaluate the efficacy of Albis (Daewoong Pharmaceutical Co., Ltd.) for the prevention of gastric mucosal injury caused by aspirin. METHODS: Aspirin users were enrolled and randomized into the Albis or placebo group. Screening and follow-up endoscopy were performed for modified Lanza scores (MLSs). Primary outcome was measured by the incidence rate of peptic ulcer, and secondary outcomes were measured by the incidence rate of gastritis, improvement in MLS and subjective symptoms. RESULTS: In total, 81 aspirin users were randomized, 43 in the Albis group and 38 in the placebo group. There was no incidence of peptic ulcer in both groups. The incidence of gastritis was significantly higher in the placebo group (44.4% vs. 10.0%, p=0.003); however, the scores of mucosal edema, hyperemia and hemorrhage were not statistically different between the two groups (p>0.05). The frequency of subjective symptoms were more improved in the Albis group than in the placebo group (p=0.023). CONCLUSIONS: The incidence of gastritis was lower in the group that received low dose aspirin and Albis. The development of peptic ulcer due to long-term use of aspirin might be prevented with concomitant use of Albis. PMID- 27196738 TI - MUTZ-3 Langerhans cell maturation and CXCL12 independent migration in reconstructed human gingiva. AB - Here we describe a reconstructed full thickness human oral mucosa (gingiva) equivalent with integrated Langerhans Cells (GE-LC) and use it to compare LC activation and migration from oral versus skin epithelium. The physiologically representative models consist of differentiated reconstructed epithelium (keratinocytes and Langerhans-like cells derived from the MUTZ-3 cell line) on a fibroblast-populated collagen hydrogel which serves as a lamina propria for gingiva and dermis for skin. Topical exposure of GE-LC and the skin equivalent (SE-LC) to sub-toxic concentrations of the allergens cinnamaldehyde, resorcinol and nickel sulphate, resulted in LC migration out of the epithelia. Neutralizing antibody to CXCL12 blocked allergen-induced LC migration in SE-LC but not in GE LC. Also, gingival fibroblasts secreted very low amounts of CXCL12 compared to skin fibroblasts even when stimulated with rhTNFalpha or rhIL-1alpha. Surprisingly, cinnamaldehyde exposure of GE-LC resulted in an increase in MUTZ-3 LC and CD83 mRNA in the hydrogel but did not result in an increase in CD1a+ cells in the collagen hydrogel (as was observed for SE-LC. These results indicate that in gingiva, upon allergen exposure, MUTZ-3 LC migrate in a CXCL12 independent manner from epithelium-to-lamina propria and in doing so mature become CD1a- and increase CD83+ mRNA. These physiologically relevant in vitro models which not only are human but which also resemble specific tissues, may aid in the identification of factors regulating immune stimulation which in turn will aid the development of therapeutic interventions for allergy and inflammation, anti cancer vaccines as well as improving diagnostics for skin and oral allergy. PMID- 27196735 TI - Cellular Architecture Regulates Collective Calcium Signaling and Cell Contractility. AB - A key feature of multicellular systems is the ability of cells to function collectively in response to external stimuli. However, the mechanisms of intercellular cell signaling and their functional implications in diverse vascular structures are poorly understood. Using a combination of computational modeling and plasma lithography micropatterning, we investigate the roles of structural arrangement of endothelial cells in collective calcium signaling and cell contractility. Under histamine stimulation, endothelial cells in self assembled and microengineered networks, but not individual cells and monolayers, exhibit calcium oscillations. Micropatterning, pharmacological inhibition, and computational modeling reveal that the calcium oscillation depends on the number of neighboring cells coupled via gap junctional intercellular communication, providing a mechanistic basis of the architecture-dependent calcium signaling. Furthermore, the calcium oscillation attenuates the histamine-induced cytoskeletal reorganization and cell contraction, resulting in differential cell responses in an architecture-dependent manner. Taken together, our results suggest that endothelial cells can sense and respond to chemical stimuli according to the vascular architecture via collective calcium signaling. PMID- 27196739 TI - Inhibition of beta-Catenin to Overcome Endocrine Resistance in Tamoxifen Resistant Breast Cancer Cell Line. AB - BACKGROUND: The beta-catenin signaling is important in cell growth and differentiation and is frequently dysregulated in various cancers. The most well known mechanism of endocrine resistance is cross-talk between the estrogen receptor (ER) and other growth factor signaling, such as phosphatidylinositol-3 kinase (PI3K)/Akt and the mammalian target of rapamycin (mTOR) signaling pathway. In the present study, we investigated whether beta-catenin could be a potential target to overcome endocrine resistance in breast cancer. METHODS: We established tamoxifen-resistant (TamR) cell line via long-term exposure of MCF-7 breast cancer cells to gradually increasing concentrations of tamoxifen. The levels of protein expression and mRNA transcripts were determined using western blot analysis and real-time quantitative PCR. The transcriptional activity of beta catenin was measured using luciferase activity assay. RESULTS: TamR cells showed a mesenchymal phenotype, and exhibited a relatively decreased expression of ER and increased expression of human epidermal growth factor receptor 2 and the epidermal growth factor receptor. We confirmed that the expression and transcriptional activity of beta-catenin were increased in TamR cells compared with control cells. The expression and transcriptional activity of beta-catenin were inhibited by beta-catenin small-molecule inhibitor, ICG-001 or beta-catenin siRNA. The viability of TamR cells, which showed no change after treatment with tamoxifen, was reduced by ICG-001 or beta-catenin siRNA. The combination of ICG 001 and mTOR inhibitor, rapamycin, yielded an additive effect on the inhibition of viability in TamR cells. CONCLUSION: These results suggest that beta-catenin plays a role in tamoxifen-resistant breast cancer, and the inhibition of beta catenin may be a potential target in tamoxifen-resistant breast cancer. PMID- 27196741 TI - Critical evaluation and methodological positioning of the transdermal microdialysis technique. A review. PMID- 27196740 TI - Parathyroidectomy Improves Restless Leg Syndrome in Patients on Hemodialysis. AB - BACKGROUND: Restless leg syndrome (RLS) is a sleep disorder with high prevalence among patients on hemodialysis. It has been postulated that high phosphate and high parathyroid hormone may be implicated in its pathogenesis. Standard international criteria and face-to-face interview are not always applied. METHODS: this was an interventional prospective study in which 19 patients (6 men, aged 48+/-11 years) with severe hyperparathyroidism were evaluated. RLS diagnosis and rating scale were accessed based on the International RLS Study Group pre- and post-parathyroidectomy. Patients also underwent standard polysomnography. RESULTS: At baseline, RLS was present in 10 patients (52.6%), and pain was the most reported symptom associated with the diagnosis. Patients with RLS had higher serum phosphate (p = 0.008) that remained independently associated with RLS in a logistic regression model, adjusted for hemoglobin, age and gender (HR = 7.28;CI = 1.14-46.3, p = 0.035). After parathyroidectomy, there was a reduction of serum parathyroid hormone, phosphate, calcium and alkaline phosphatase, and an increase of 25(OH)-vitamin D, and Fetuin-A. Parathyroidectomy alleviated RLS (from 52% to 21%; p = 0.04), which was accompanied by a decrease in severity scale, in association with relief of pain and pruritus. Polysomnography in these patients showed an improvement of sleep parameters as measured by sleep efficiency, sleep latency and percentage of REM sleep. CONCLUSION: RLS is associated with high levels of phosphate in patients with severe secondary hyperparathyroidism on hemodialysis. Pain is most reported complain in these patients. Parathyroidectomy provided an opportunity to relief RLS. Whether the reduction of serum phosphorus or parathyroid hormone contributed to this improvement merits further investigation. PMID- 27196743 TI - Delivery of the high-mobility group box 1 box A peptide using heparin in the acute lung injury animal models. AB - In this study, the efficacy of the high-mobility group box-1 box A (HMGB1A)/heparin complex was evaluated for the treatment of acute lung injury (ALI). HMGB1A is an antagonist against wild-type high-mobility group box-1 (wtHMGB1), a pro-inflammatory cytokine that is involved in ALIs. HMGB1A has positive charges and can be captured in the mucus layer after intratracheal administration. To enhance the delivery and therapeutic efficiency of HMGB1A, the HMGB1A/heparin complex was produced using electrostatic interactions, with the expectation that the nano-sized complex with a negative surface charge could efficiently penetrate the mucus layer. Additionally, heparin itself had an anti inflammatory effect. Complex formation with HMGB1A and heparin was confirmed by atomic force microscopy. The particle size and surface charge of the HMGB1A/heparin complex at a 1:1 weight ratio were 113nm and -25mV, respectively. Intratracheal administration of the complex was performed into an ALI animal model. The results showed that the HMGB1A/heparin complex reduced pro inflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-1beta, more effectively than HMGB1A or heparin alone. Hematoxylin and eosin staining confirmed the decreased inflammatory reaction in the lungs after delivery of the HMGB1A/heparin complex. In conclusion, the HMGB1A/heparin complex might be useful to treat ALI. PMID- 27196745 TI - Emission of particulate matter from a desktop three-dimensional (3D) printer. AB - Desktop three-dimensional (3D) printers are becoming commonplace in business offices, public libraries, university labs and classrooms, and even private homes; however, these settings are generally not designed for exposure control. Prior experience with a variety of office equipment devices such as laser printers that emit ultrafine particles (UFP) suggests the need to characterize 3D printer emissions to enable reliable risk assessment. The aim of this study was to examine factors that influence particulate emissions from 3D printers and characterize their physical properties to inform risk assessment. Emissions were evaluated in a 0.5-m(3) chamber and in a small room (32.7 m(3)) using real-time instrumentation to measure particle number, size distribution, mass, and surface area. Factors evaluated included filament composition and color, as well as the manufacturer-provided printer emissions control technologies while printing an object. Filament type significantly influenced emissions, with acrylonitrile butadiene styrene (ABS) emitting larger particles than polylactic acid (PLA), which may have been the result of agglomeration. Geometric mean particle sizes and total particle (TP) number and mass emissions differed significantly among colors of a given filament type. Use of a cover on the printer reduced TP emissions by a factor of 2. Lung deposition calculations indicated a threefold higher PLA particle deposition in alveoli compared to ABS. Desktop 3D printers emit high levels of UFP, which are released into indoor environments where adequate ventilation may not be present to control emissions. Emissions in nonindustrial settings need to be reduced through the use of a hierarchy of controls, beginning with device design, followed by engineering controls (ventilation) and administrative controls such as choice of filament composition and color. PMID- 27196744 TI - Loss of presenilin function is associated with a selective gain of APP function. AB - Presenilin 1 (PS1) is an essential gamma-secretase component, the enzyme responsible for amyloid precursor protein (APP) intramembraneous cleavage. Mutations in PS1 lead to dominant-inheritance of early-onset familial Alzheimer's disease (FAD). Although expression of FAD-linked PS1 mutations enhances toxic Abeta production, the importance of other APP metabolites and gamma-secretase substrates in the etiology of the disease has not been confirmed. We report that neurons expressing FAD-linked PS1 variants or functionally deficient PS1 exhibit enhanced axodendritic outgrowth due to increased levels of APP intracellular C terminal fragment (APP-CTF). APP expression is required for exuberant neurite outgrowth and hippocampal axonal sprouting observed in knock-in mice expressing FAD-linked PS1 mutation. APP-CTF accumulation initiates CREB signaling cascade through an association of APP-CTF with Galphas protein. We demonstrate that pathological PS1 loss-of-function impinges on neurite formation through a selective APP gain-of-function that could impact on axodendritic connectivity and contribute to aberrant axonal sprouting observed in AD patients. PMID- 27196746 TI - Transient Elimination of Posterior Right Ventricular Outflow Tract Ectopy by Sternal Pressure. AB - BACKGROUND: Ventricular ectopy (VE) originating in the right ventricular outflow tract (RVOT) is a common arrhythmia. Mechanisms triggering or eliminating VE from RVOT are not entirely understood. METHODS AND RESULTS: A patient with frequent, symptomatic VE underwent an electrophysiologic study: VE origin was mapped by NavX 3D navigation (St. Jude Medical, Inc., St. Paul, MN, USA). Incidental pressure applied manually to the sternum reproducibly eliminated VE for the time of exposure. Radiofrequency-ablation was successfully performed in the posterior RVOT. CONCLUSION: The mechanism resulting in VE suppression remains speculative, since a mechanical alteration of the substrate for VE in the posterior RVOT by sternal pressure seems unlikely. "Mechano-electrical feedback" might have been the mechanism operative in this case. PMID- 27196747 TI - Management of Acute Alcohol Withdrawal Syndrome in Critically Ill Patients. AB - Approximately 16-31% of patients in the intensive care unit (ICU) have an alcohol use disorder and are at risk for developing alcohol withdrawal syndrome (AWS). Patients admitted to the ICU with AWS have an increased hospital and ICU length of stay, longer duration of mechanical ventilation, higher costs, and increased mortality compared with those admitted without an alcohol-related disorder. Despite the high prevalence of AWS among ICU patients, no guidelines for the recognition or management of AWS or delirium tremens in the critically ill currently exist, leading to tremendous variability in clinical practice. Goals of care should include immediate management of dehydration, nutritional deficits, and electrolyte derangements; relief of withdrawal symptoms; prevention of progression of symptoms; and treatment of comorbid illnesses. Symptom-triggered treatment of AWS with gamma-aminobutyric acid receptor agonists is the cornerstone of therapy. Benzodiazepines (BZDs) are most studied and are often the preferred first-line agents due to their efficacy and safety profile. However, controversy still exists as to who should receive treatment, how to administer BZDs, and which BZD to use. Although most patients with AWS respond to usual doses of BZDs, ICU clinicians are challenged with managing BZD-resistant patients. Recent literature has shown that using an early multimodal approach to managing BZD-resistant patients appears beneficial in rapidly improving symptoms. This review highlights the results of recent promising studies published between 2011 and 2015 evaluating adjunctive therapies for BZD-resistant alcohol withdrawal such as antiepileptics, baclofen, dexmedetomidine, ethanol, ketamine, phenobarbital, propofol, and ketamine. We provide guidance on the places in therapy for select agents for management of critically ill patients in the presence of AWS. PMID- 27196748 TI - Long Term Positive Effect of Grassland Restoration on Plant Diversity - Success or Not? AB - Restoration is important for biodiversity conservation worldwide, but surprisingly little is known about its efficiency in a long-term perspective. In this study, we re-examined Swedish semi-natural grasslands 12-20 years after the restoration, by comparing field inventories of vascular plant species diversity made in 2001 with follow-up inventories in 2012. We also analysed restoration effect in relation to six environmental factors and used continuously managed semi-natural grasslands as references of desired state after restoration. We found that total species richness increased over time but not to reference levels, while there were no significant changes in species density or number of grassland specialists. However, the overall species composition in the restored sites, as well as grassland specialist composition, now largely resembled reference conditions. Fertilisation and time between abandonment and restoration were the only environmental variables that affected total species composition change, while site area affected change in grassland specialist composition. Our results show that restoration of semi-natural grasslands can contribute to conservation of semi-natural habitats and their associated biodiversity. Yet, due to the vague restoration goals for these sites, it is difficult to evaluate the restoration success, which emphasise the general need for clear and measurable goals. PMID- 27196749 TI - Preclinical Evaluation of AMG 337, a Highly Selective Small Molecule MET Inhibitor, in Hepatocellular Carcinoma. AB - Aberrant hepatocyte growth factor (HGF)/MET signaling has been implicated in hepatocarcinogenesis, suggesting that MET may serve as an attractive therapeutic target in hepatocellular carcinoma. We sought to investigate the in vitro and in vivo antitumor activity of AMG 337, a potent and highly selective small molecule MET kinase inhibitor, in preclinical models of hepatocellular carcinoma. The antiproliferative activity of AMG 337 was evaluated across a panel of hepatocellular carcinoma cell lines in a viability assay. Daily oral administration was used to evaluate the in vivo antitumor activity of AMG 337 in two patient-derived xenograft (PDX) models of hepatocellular carcinoma (LI0612 and LI1078). AMG 337 exerted potent antiproliferative activity against 2 of 40 hepatocellular carcinoma cell lines, namely, MHCC97H (IC50, 0.015 MUmol/L) and HCCLM3 (IC50, 0.025 MUmol/L). Both sensitive cell lines showed MET amplification (MET/CEN-7 >2.0) assessed by FISH, and high MET expression (3+ IHC) assessed by IHC. AMG 337 potently inhibited p-MET in all cell lines with detectable levels of total MET. However, the dose-dependent inhibition of downstream effectors of HGF/MET signaling, including p-GAB1, p-AKT, and p-ERK, was limited to those cell lines sensitive to AMG 337 in a viability assay (MHCC97H and HCCLM3). AMG 337 significantly inhibited tumor growth at all doses tested in the MET-amplified and MET-high-expressing hepatocellular carcinoma PDX model LI0612 and had no effect on tumor growth in the non-MET-amplified and MET-low-expressing hepatocellular carcinoma PDX model LI1078. AMG 337 represents a promising and novel therapeutic strategy for targeting hepatocellular carcinomas with a dependence on HGF/MET signaling. Mol Cancer Ther; 15(6); 1227-37. (c)2016 AACR. PMID- 27196750 TI - Therapeutic Targeting of miR-29b/HDAC4 Epigenetic Loop in Multiple Myeloma. AB - Epigenetic abnormalities are common in hematologic malignancies, including multiple myeloma, and their effects can be efficiently counteracted by a class of tumor suppressor miRNAs, named epi-miRNAs. Given the oncogenic role of histone deacetylases (HDAC) in multiple myeloma, we investigated whether their activity could be antagonized by miR-29b, a well-established epi-miRNA. We demonstrated here that miR-29b specifically targets HDAC4 and highlighted that both molecules are involved in a functional loop. In fact, silencing of HDAC4 by shRNAs inhibited multiple myeloma cell survival and migration and triggered apoptosis and autophagy, along with the induction of miR-29b expression by promoter hyperacetylation, leading to the downregulation of prosurvival miR-29b targets (SP1, MCL-1). Moreover, treatment with the pan-HDAC inhibitor SAHA upregulated miR-29b, overcoming the negative control exerted by HDAC4. Importantly, overexpression or inhibition of miR-29b, respectively, potentiated or antagonized SAHA activity on multiple myeloma cells, as also shown in vivo by a strong synergism between miR-29b synthetic mimics and SAHA in a murine xenograft model of human multiple myeloma. Altogether, our results shed light on a novel epigenetic circuitry regulating multiple myeloma cell growth and survival and open new avenues for miR-29b-based epi-therapeutic approaches in the treatment of this malignancy. Mol Cancer Ther; 15(6); 1364-75. (c)2016 AACR. PMID- 27196751 TI - Activating Transcription Factor 3 Expression as a Marker of Response to the Histone Deacetylase Inhibitor Pracinostat. AB - Improved treatment strategies are required for bladder cancer due to frequent recurrence of low-grade tumors and poor survival rate from high-grade tumors with current therapies. Histone deacetylase inhibitors (HDACi), approved as single agents for specific lymphomas, have shown promising preclinical results in solid tumors but could benefit from identification of biomarkers for response. Loss of activating transcription factor 3 (ATF3) expression is a feature of bladder tumor progression and correlates with poor survival. We investigated the utility of measuring ATF3 expression as a marker of response to the HDACi pracinostat in bladder cancer models. Pracinostat treatment of bladder cancer cell lines reactivated the expression of ATF3, correlating with significant alteration in proliferative, migratory, and anchorage-dependent growth capacities. Pracinostat also induced growth arrest at the G0-G1 cell-cycle phase, coincident with the activation of tumor suppressor genes. In mouse xenograft bladder cancer models, pracinostat treatment significantly reduced tumor volumes compared with controls, accompanied by reexpression of ATF3 in nonproliferating cells from early to late stage of therapy and in parallel induced antiangiogenesis and apoptosis. Importantly, cells in which ATF3 expression was depleted were less sensitive to pracinostat treatment in vitro, exhibiting significantly higher proliferative and migratory properties. In vivo, control xenograft tumors were significantly more responsive to treatment than ATF3 knockdown xenografts. Thus, reactivation of ATF3 is an important factor in determining sensitivity to pracinostat treatment, both in vitro and in vivo, and could serve as a potential biomarker of response and provide a rationale for therapeutic utility in HDACi-mediated treatments for bladder cancer. Mol Cancer Ther; 15(7); 1726-39. (c)2016 AACR. PMID- 27196752 TI - The Discovery and Characterization of K-756, a Novel Wnt/beta-Catenin Pathway Inhibitor Targeting Tankyrase. AB - The Wnt/beta-catenin pathway is a well-known oncogenic pathway. Its suppression has long been considered as an important challenge in treating cancer patients. Among colon cancer patients in particular, most patients carry an adenomatous polyposis coli (APC) mutation that leads to an aberration of Wnt/beta-catenin pathway. To discover the small molecule inhibitors of the Wnt/beta-catenin pathway, we conducted high-throughput screening in APC-mutant colon cancer DLD-1 cells using a transcriptional reporter assay, which identified a selective Wnt/beta-catenin pathway inhibitor, K-756. K-756 stabilizes Axin and reduces active beta-catenin, and inhibits the genes downstream of endogenous Wnt/beta catenin. We subsequently identified that K-756 is a tankyrase (TNKS) inhibitor. TNKS, which belongs to the PARP family, poly-ADP ribosylates Axin and promotes Axin degradation via the proteasome pathway. K-756 binds to the induced pocket of TNKS and inhibits its enzyme activity. Moreover, PARP family enzyme assays showed that K-756 is a selective TNKS inhibitor. K-756 inhibited the cell growth of APC mutant colorectal cancer COLO 320DM and SW403 cells by inhibiting the Wnt/beta catenin pathway. An in vivo study showed that the oral administration of K-756 inhibited the Wnt/beta-catenin pathway in colon cancer xenografts in mice. To further explore the therapeutic potential of K-756, we also evaluated the effects of K-756 in non-small cell lung cancer cells. Although a single treatment of K 756 did not induce antiproliferative activity, when K-756 was combined with an EGFR inhibitor (gefitinib), it showed a strong synergistic effect. Therefore, K 756, a novel selective TNKS inhibitor, could be a leading compound in the development of anticancer agents. Mol Cancer Ther; 15(7); 1525-34. (c)2016 AACR. PMID- 27196753 TI - Osimertinib (AZD9291) Enhanced the Efficacy of Chemotherapeutic Agents in ABCB1- and ABCG2-Overexpressing Cells In Vitro, In Vivo, and Ex Vivo. AB - The overexpression of ATP-binding cassette (ABC) transporters has been proved to be a major trigger for multidrug resistance (MDR) in certain types of cancer. In our study, we investigated whether osimertinib (AZD9291), a third-generation irreversible tyrosine kinase inhibitor of both activating EGFR mutations and resistance-associated T790M point mutation, could reverse MDR induced by ABCB1 and ABCG2 in vitro, in vivo, and ex vivo Our results showed that osimertinib significantly increased the sensitivity of ABCB1- and ABCG2-overexpressing cells to their substrate chemotherapeutic agents in vitro and in the model of ABCB1 overexpressing KBv200 cell xenograft in nude mice. Mechanistically, osimertinib increased the intracellular accumulations of doxorubicin (DOX) and Rhodamine 123 (Rho 123) by inhibiting the efflux function of the transporters in ABCB1- or ABCG2-overexpressing cells but not in their parental sensitive cells. Furthermore, osimertinib stimulated the ATPase activity of both ABCB1 and ABCG2 and competed with the [(125)I] iodoarylazidoprazosin photolabeling bound to ABCB1 or ABCG2, but did not alter the localization and expression of ABCB1 or ABCG2 in mRNA and protein levels nor the phosphorylations of EGFR, AKT, and ERK. Importantly, osimertinib also enhanced the cytotoxicity of DOX and intracellular accumulation of Rho 123 in ABCB1-overexpressing primary leukemia cells. Overall, these findings suggest osimertinib reverses ABCB1- and ABCG2-mediated MDR via inhibiting ABCB1 and ABCG2 from pumping out chemotherapeutic agents and provide possibility for cancer combinational therapy with osimertinib in the clinic. Mol Cancer Ther; 15(8); 1845-58. (c)2016 AACR. PMID- 27196754 TI - Concomitant Inhibition of PI3Kbeta and BRAF or MEK in PTEN-Deficient/BRAF-Mutant Melanoma Treatment: Preclinical Assessment of SAR260301 Oral PI3Kbeta-Selective Inhibitor. AB - Class IA PI3K pathway activation resulting from PTEN deficiency has been associated with lack of sensitivity of melanoma to BRAF kinase inhibitors. Although previous studies have shown synergistic activity when pan-PI3K inhibitors were combined with MAPK inhibitors in the treatment of melanoma exhibiting concurrent genetic abnormalities, overlapping adverse events in patients limit optimal dosing and clinical application. With the aim of specifically targeting PTEN-deficient cancers and minimizing the potential for on target toxicity when inhibiting multiple PI3K isoforms, we developed a program to discover PI3Kbeta-selective kinase inhibitors and identified SAR260301 as a potent PI3Kbeta-selective, orally available compound, which is now in clinical development. Herein, we provide a detailed biological characterization of SAR260301, and show that this compound has outstanding biochemical and cellular selectivity for the PI3Kbeta isoform versus the alpha, delta, and gamma isoforms and a large panel of protein and lipid kinases. We demonstrate that SAR260301 blocks PI3K pathway signaling preferentially in PTEN-deficient human tumor models, and has synergistic antitumor activity when combined with vemurafenib (BRAF inhibitor) or selumetinib (MEK inhibitor) in PTEN-deficient/BRAF-mutated human melanoma tumor models. Combination treatments were very well tolerated, suggesting the potential for a superior safety profile at optimal dosing using selective compounds to inhibit multiple signaling pathways. Together, these experiments provide a preclinical proof-of-concept for safely combining inhibitors of PI3Kbeta and BRAF or MEK kinase modulators to improve antitumor activity in PTEN-deficient/BRAF-mutant melanoma, and support the evaluation of SAR260301-based combinations in clinical studies. Mol Cancer Ther; 15(7); 1460 71. (c)2016 AACR. PMID- 27196755 TI - Loss of PKCdelta Induces Prostate Cancer Resistance to Paclitaxel through Activation of Wnt/beta-Catenin Pathway and Mcl-1 Accumulation. AB - Prostate cancer is the leading cause of cancer-related death among men in developed countries. Although castration therapy is initially effective, prostate cancers progress to hormone-refractory disease and in this case taxane-based chemotherapy is widely used. Castration-resistant prostate cancer cells often develop resistance to chemotherapy agents and the search for new therapeutic strategies is necessary. In this article, we demonstrate that PKCdelta silencing favors mitotic arrest after paclitaxel treatment in PC3 and LNCaP cells; however, this is associated with resistance to paclitaxel-induced apoptosis. In prostate cancer cells, PKCdelta seems to exert a proapoptotic role, acting as a negative regulator of the canonical Wnt/beta-catenin pathway. PKCdelta silencing induces activation of Wnt/beta-catenin pathway and the expression of its target genes, including Aurora kinase A, which is involved in activation of Akt and both factors play a key role in GSK3beta inactivation and consequently in the stabilization of beta-catenin and antiapoptotic protein Mcl-1. We also show that combined treatments with paclitaxel and Wnt/beta-catenin or Akt inhibitors improve the apoptotic response to paclitaxel, even in the absence of PKCdelta. Finally, we observe that high Gleason score prostate tumors lose PKCdelta expression and this correlates with higher activation of beta-catenin, inactivation of GSK3beta, and higher levels of Aurora kinase A and Mcl-1 proteins. These findings suggest that targeting Wnt/beta-catenin or Akt pathways may increase the efficacy of taxane chemotherapy in advanced human prostate cancers that have lost PKCdelta expression. Mol Cancer Ther; 15(7); 1713-25. (c)2016 AACR. PMID- 27196756 TI - The Effect of F877L and T878A Mutations on Androgen Receptor Response to Enzalutamide. AB - Treatment-induced mutations in the ligand-binding domain of the androgen receptor (AR) are known to change antagonists into agonists. Recently, the F877L mutation has been described to convert enzalutamide into an agonist. This mutation was seen to co-occur in the endogenous AR allele of LNCaP cells, next to the T878A mutation. Here, we studied the effects of enzalutamide on the F877L and T878A mutants, as well as the double-mutant AR (F877L/T878A). Molecular modeling revealed favorable structural changes in the double-mutant AR that lead to a decrease in steric clashes for enzalutamide. Ligand-binding assays confirmed that the F877L mutation leads to an increase in relative binding affinity for enzalutamide, but only the combination with the T878A mutation resulted in a strong agonistic activity. This correlated with changes in coregulator recruitment and chromatin interactions. Our data show that enzalutamide is only a very weak partial agonist of the AR F877L, and a strong partial agonist of the double-mutant AR. Mol Cancer Ther; 15(7); 1702-12. (c)2016 AACR. PMID- 27196742 TI - Barriers to inhaled gene therapy of obstructive lung diseases: A review. AB - Knowledge of genetic origins of obstructive lung diseases has made inhaled gene therapy an attractive alternative to the current standards of care that are limited to managing disease symptoms. Initial lung gene therapy clinical trials occurred in the early 1990s following the discovery of the genetic defect responsible for cystic fibrosis (CF), a monogenic disorder. However, despite over two decades of intensive effort, gene therapy has yet to help patients with CF or any other obstructive lung disease. The slow progress is due in part to poor understanding of the biological barriers to inhaled gene therapy. Encouragingly, clinical trials have shown that inhaled gene therapy with various viral vectors and non-viral gene vectors is well tolerated by patients, and continued research has provided valuable lessons and resources that may lead to future success of this therapeutic strategy. In this review, we first introduce representative obstructive lung diseases and examine limitations of currently available therapeutic options. We then review key components for successful execution of inhaled gene therapy, including gene delivery systems, primary physiological barriers and strategies to overcome them, and advances in preclinical disease models with which the most promising systems may be identified for human clinical trials. PMID- 27196758 TI - Src as a Therapeutic Target in Biliary Tract Cancer. AB - Src, a nonreceptor tyrosine kinase, is involved in a number of cancer-related signaling pathways and aberrantly activated in biliary tract cancer (BTC). This study aimed to elucidate the potential role of Src as a therapeutic target in BTC. We tested bosutinib, an orally active c-Src/Abl kinase inhibitor, alone or in combination with cytotoxic agents using 9 human BTC cell lines: SNU-245, SNU 308, SNU-478, SNU-869, SNU-1079, SNU-1196, HuCCT1, TFK-1, and EGI-1. Of these, SNU-308 and SNU-478 were relatively sensitive to bosutinib. Bosutinib abrogated phosphorylation of Src and its downstream molecules, and significantly increased G1 cell-cycle arrest and apoptosis. Bosutinib significantly inhibited cell migration and invasion and decreased epithelial-mesenchymal transition markers. Bosutinib combined with gemcitabine or cisplatin showed synergistic antiproliferative and antimigratory effects. In addition, this combination further inhibited phosphorylation of Src and its downstream molecules and decreased epithelial-mesenchymal transition marker expression compared with bosutinib alone. We established a SNU-478 xenograft model for in vivo experiments, because SNU-478 was more tumorigenic than SNU-308. Bosutinib combined with gemcitabine or cisplatin showed significantly more potent antitumor effects than bosutinib alone. Bosutinib combined with gemcitabine further decreased Ki-67 expression and Src phosphorylation, and further increased TUNEL expression. Our data suggest that Src might be a potential therapeutic target in BTC. Bosutinib demonstrated promising antitumor activity alone or in combination with gemcitabine or cisplatin in BTC cells, which supports further clinical development in patients with advanced BTC. Mol Cancer Ther; 15(7); 1515-24. (c)2016 AACR. PMID- 27196757 TI - Chromatin Regulators as a Guide for Cancer Treatment Choice. AB - The limited capacity to predict a patient's response to distinct chemotherapeutic agents is a major hurdle in cancer management. The efficiency of a large fraction of current cancer therapeutics (radio- and chemotherapies) is influenced by chromatin structure. Reciprocally, alterations in chromatin organization may affect resistance mechanisms. Here, we explore how the misexpression of chromatin regulators-factors involved in the establishment and maintenance of functional chromatin domains-can inform about the extent of docetaxel response. We exploit Affymetrix and NanoString gene expression data for a set of chromatin regulators generated from breast cancer patient-derived xenograft models and patient samples treated with docetaxel. Random Forest classification reveals specific panels of chromatin regulators, including key components of the SWI/SNF chromatin remodeler, which readily distinguish docetaxel high-responders and poor responders. Further exploration of SWI/SNF components in the comprehensive NCI-60 dataset reveals that the expression inversely correlates with docetaxel sensitivity. Finally, we show that loss of the SWI/SNF subunit BRG1 (SMARCA4) in a model cell line leads to enhanced docetaxel sensitivity. Altogether, our findings point toward chromatin regulators as biomarkers for drug response as well as therapeutic targets to sensitize patients toward docetaxel and combat drug resistance. Mol Cancer Ther; 15(7); 1768-77. (c)2016 AACR. PMID- 27196760 TI - TRX-E-002-1 Induces c-Jun-Dependent Apoptosis in Ovarian Cancer Stem Cells and Prevents Recurrence In Vivo. AB - Chemoresistance is a major hurdle in the management of patients with epithelial ovarian cancer and is responsible for its high mortality. Studies have shown that chemoresistance is due to the presence of a subgroup of cancer cells with stemness properties and a high capacity for tumor repair. We have developed a library of super-benzopyran analogues to generate potent compounds that can induce cell death in chemoresistant cancer stem cells. TRX-E-002-1 is identified as the most potent analogue and can induce cell death in all chemoresistant CD44(+)/MyD88(+) ovarian cancer stem cells tested (IC50 = 50 nmol/L). TRX-E-002-1 is also potent against spheroid cultures formed from cancer stem cells, chemosensitive CD44(-)/MyD88(-) ovarian cancer cells, and heterogeneous cultures of ovarian cancer cells. Cell death was associated with the phosphorylation and increased levels of c-Jun and induction of caspases. In vivo, TRX-E-002-1 given as daily intraperitoneal monotherapy at 100 mg/kg significantly decreased intraperitoneal tumor burden compared with vehicle control. When given in combination with cisplatin, animals receiving the combination of cisplatin and TRX-E-002-1 showed decreased tumor burden compared with each monotherapy. Finally, TRX-E-002-1 given as maintenance treatment after paclitaxel significantly delayed disease recurrence. Our results suggest that TRX-E-002-1 may fill the current need for better therapeutic options in the control and management of recurrent ovarian cancer and may help improve patient survival. Mol Cancer Ther; 15(6); 1279-90. (c)2016 AACR. PMID- 27196759 TI - MSK1-Mediated beta-Catenin Phosphorylation Confers Resistance to PI3K/mTOR Inhibitors in Glioblastoma. AB - Glioblastoma (GBM) represents a compelling disease for kinase inhibitor therapy because most of these tumors harbor genetic alterations that result in aberrant activation of growth factor-signaling pathways. The PI3K/mammalian target of the rapamycin (mTOR) pathway is dysregulated in over 50% of human GBM but remains a challenging clinical target. Inhibitors against PI3K/mTOR mediators have limited clinical efficacy as single agents. We investigated potential bypass mechanisms to PI3K/mTOR inhibition using gene expression profiling before and after PI3K inhibitor treatment by Affymetrix microarrays. Mitogen- and stress-activated protein kinase 1 (MSK1) was markedly induced after PI3K/mTOR inhibitor treatment and disruption of MSK1 by specific shRNAs attenuated resistance to PI3K/mTOR inhibitors in glioma-initiating cells (GIC). Further investigation showed that MSK1 phosphorylates beta-catenin and regulates its nuclear translocation and transcriptional activity. The depletion of beta-catenin potentiated PI3K/mTOR inhibitor-induced cytotoxicity and the inhibition of MSK1 synergized with PI3K/mTOR inhibitors to extend survival in an intracranial animal model and decreased phosphorylation of beta-catenin at Ser(552) These observations suggest that MSK1/beta-catenin signaling serves as an escape survival signal upon PI3K/mTOR inhibition and provides a strong rationale for the combined use of PI3K/mTOR and MSK1/beta-catenin inhibition to induce lethal growth inhibition in human GBM. Mol Cancer Ther; 15(7); 1656-68. (c)2016 AACR. PMID- 27196762 TI - Suppression of SRC Signaling Is Effective in Reducing Synergy between Glioblastoma and Stromal Cells. AB - Glioblastoma cells efficiently interact with and infiltrate the surrounding normal tissue, rendering surgical resection and adjuvant chemo/radiotherapy ineffective. New therapeutic targets, able to interfere with glioblastoma's capacity to synergize with normal brain tissue, are currently under investigation. The compound Si306, a pyrazolo[3,4-d]pyrimidine derivative, selected for its favorable activity against SRC, was tested in vitro and in vivo on glioblastoma cell lines. In vivo, combination treatment with Si306 and radiotherapy was strongly active in reducing U-87 xenograft growth with respect to control and single treatments. The histology revealed a significant difference in the stromal compartment of tumoral tissue derived from control or radiotherapy treated samples with respect to Si306-treated samples, showing in the latter a reduced presence of collagen and alpha-SMA-positive cells. This effect was paralleled in vitro by the capacity of Si306 to interfere with myofibroblastic differentiation of normal fibroblasts induced by U-87 cells. In the presence of Si306, TGF-beta released by U-87 cells, mainly in hypoxia, was ineffective in upregulating alpha-SMA and beta-PDGFR in fibroblasts. Si306 efficiently reached the brain and significantly prolonged the survival of mice orthotopically injected with U-87 cells. Drugs that target SRC could represent an effective therapeutic strategy in glioblastoma, able to block positive paracrine loop with stromal cells based on the beta-PDGFR axis and the formation of a tumor-promoting microenvironment. This approach could be important in combination with conventional treatments in the effort to reduce tumor resistance to therapy. Mol Cancer Ther; 15(7); 1535-44. (c)2016 AACR. PMID- 27196761 TI - Targeting IkappaB Kinase beta/NF-kappaB Signaling in Human Prostate Cancer by a Novel IkappaB Kinase beta Inhibitor CmpdA. AB - NF-kappaB plays an important role in many types of cancer, including prostate cancer, but the role of the upstream kinase of NF-kappaB, IKKbeta, in prostate cancer has neither been fully documented nor are there any effective IKKbeta inhibitors used in clinical settings. Here, we have shown that IKKbeta activity is mediated by multiple kinases including IKKalpha in human prostate cancer cell lines that express activated IKKbeta. IHC analysis (IHC) of human prostate cancer tissue microarrays (TMA) demonstrates that phosphorylation of IKKalpha/beta within its activation loop gradually increases in low to higher stage tumors as compared with normal tissue. The expression of cell proliferation and survival markers (Ki-67, Survivin) and epithelial-to-mesenchymal transition (EMT) markers (Slug, Snail), as well as cancer stem cell (CSC)-related transcription factors (Nanog, Sox2, Oct-4), also increase in parallel among the respective TMA samples analyzed. IKKbeta, but not NF-kappaB, is found to regulate Nanog, which, in turn, modulates the levels of Oct4, Sox2, Snail, and Slug, indicating an essential role of IKKbeta in regulating CSCs and EMT. The novel IKKbeta inhibitor CmpdA inhibits constitutively activated IKKbeta/NF-kappaB signaling, leading to induction of apoptosis and inhibition of proliferation, migration, and stemness in these cells. CmpdA also significantly inhibits tumor growth in xenografts without causing apparent in vivo toxicity. Furthermore, CmpdA and docetaxel act synergistically to inhibit proliferation of prostate cancer cells. These results indicate that IKKbeta plays a pivotal role in prostate cancer, and targeting IKKbeta, including in combination with docetaxel, may be a potentially useful strategy for treating advanced prostate cancer. Mol Cancer Ther; 15(7); 1504-14. (c)2016 AACR. PMID- 27196763 TI - Infiltrating T Cells Promote Bladder Cancer Progression via Increasing IL1 >Androgen Receptor->HIF1alpha->VEGFa Signals. AB - The tumor microenvironment impacts tumor progression and individual cells, including CD4(+) T cells, which have been detected in bladder cancer tissues. The detailed mechanism of how these T cells were recruited to the bladder cancer tumor and their impact on bladder cancer progression, however, remains unclear. Using a human clinical bladder cancer sample survey and in vitro coculture system, we found that bladder cancer has a greater capacity to recruit T cells than surrounding normal bladder tissues. The consequences of higher levels of recruited T cells in bladder cancer included increased bladder cancer metastasis. Mechanism dissection revealed that infiltrating T cells might function through secreting the cytokine IL1, which increases the recruitment of T cells to bladder cancer and enhances the bladder cancer androgen receptor (AR) signaling that results in increased bladder cancer cell invasion via upregulation of hypoxia inducible factor-1alpha (HIF1alpha)/VEGFa expression. Interruption of the IL1->AR >HIF1alpha->VEGFa signals with inhibitors of HIF1alpha or VEGFa partially reversed the enhanced bladder cancer cell invasion. Finally, in vivo mouse models of xenografted bladder cancer T24 cells with CD4(+) T cells confirmed in vitro coculture studies and concluded that infiltrating CD4(+) T cells can promote bladder cancer metastasis via modulation of the IL1->AR->HIF1alpha->VEGFa signaling. Future clinical trials using small molecules to target this newly identified signaling pathway may facilitate the development of new therapeutic approaches to better suppress bladder cancer metastasis. Mol Cancer Ther; 15(8); 1943-51. (c)2016 AACR. PMID- 27196764 TI - Clinical Significance of TLR1 I602S Polymorphism for Patients with Metastatic Colorectal Cancer Treated with FOLFIRI plus Bevacizumab. AB - The purpose of this study was to evaluate the clinical significance of single nucleotide polymorphisms in TLR1, TLR2, TLR6, and TAK1 in patients with metastatic colorectal cancer (mCRC). We genotyped 9 SNPs of TLR1, TLR2, TLR6, and TAK1 in mCRC patients treated with first-line FOLFIRI (combination therapy of irinotecan, 5-fluorouracil, and folinic acid) plus bevacizumab, using a discovery cohort (TRIBE trial, n = 228) and a validation cohort (FIRE-3 trial, n = 297), and analyzed for the association with response rate (RR), progression-free survival (PFS), and overall survival (OS). There was a significant association of TLR1 rs5743618 (T1805G) with the clinical outcome. In the TRIBE cohort, a homozygous wild-type genotype (T/T) associated with a significantly lower RR compared with variant T/G and G/G genotypes (43% vs. 62%, P = 0.025), and this observation was validated in the FIRE-3 cohort (46% vs. 65%, P = 0.021). In addition, those patients with the T/T genotype had significantly worse PFS (median, 8.2 vs. 10.5 months; HR, 1.57; 95% CI, 1.09-2.28, P = 0.014) and OS (median: 19.9 vs. 27.9 months; HR, 1.63; 95% CI, 1.14-2.35, P = 0.007), compared with those with other genotypes in the TRIBE cohort. These differences remained statistically significant in multivariate analysis. Our data suggest that TLR1 rs5743618 could serve as a predictor of clinical response to FOLFIRI plus bevacizumab in patients with mCRC. Mol Cancer Ther; 15(7); 1740-5. (c)2016 AACR. PMID- 27196766 TI - Sensitizing Triple-Negative Breast Cancer to PI3K Inhibition by Cotargeting IGF1R. AB - Targeted therapies have proven invaluable in the treatment of breast cancer, as exemplified by tamoxifen treatment for hormone receptor-positive tumors and trastuzumab treatment for HER2-positive tumors. In contrast, a subset of breast cancer negative for these markers, triple-negative breast cancer (TNBC), has met limited success with pathway-targeted therapies. A large fraction of TNBCs depend on the PI3K pathway for proliferation and survival, but inhibition of PI3K alone generally has limited clinical benefit. We performed an RNAi-based genetic screen in a human TNBC cell line to identify kinases whose knockdown synergizes with the PI3K inhibitor GDC-0941 (pictilisib). We discovered that knockdown of insulin like growth factor-1 receptor (IGF1R) expression potently increased sensitivity of these cells to GDC-0941. Pharmacologic inhibition of IGF1R using OSI-906 (linsitinib) showed a strong synergy with PI3K inhibition. Furthermore, we found that the combination of GDC-0941 and OSI-906 is synergistic in 8 lines from a panel of 18 TNBC cell lines. In these cell lines, inhibition of IGF1R further decreases the activity of downstream PI3K pathway components when PI3K is inhibited. Expression analysis of the panel of TNBC cell lines indicates that the expression levels of IGF2BP3 can be used as a potential predictor for sensitivity to the PI3K/IGF1R inhibitor combination. Our data show that combination therapy consisting of PI3K and IGF1R inhibitors could be beneficial in a subset of TNBCs. Mol Cancer Ther; 15(7); 1545-56. (c)2016 AACR. PMID- 27196765 TI - PAXIP1 Potentiates the Combination of WEE1 Inhibitor AZD1775 and Platinum Agents in Lung Cancer. AB - The DNA damage response (DDR) involves a complex network of signaling events mediated by modular protein domains such as the BRCA1 C-terminal (BRCT) domain. Thus, proteins that interact with BRCT domains and are a part of the DDR constitute potential targets for sensitization to DNA-damaging chemotherapy agents. We performed a pharmacologic screen to evaluate 17 kinases, identified in a BRCT-mediated interaction network as targets to enhance platinum-based chemotherapy in lung cancer. Inhibition of mitotic kinase WEE1 was found to have the most effective response in combination with platinum compounds in lung cancer cell lines. In the BRCT-mediated interaction network, WEE1 was found in complex with PAXIP1, a protein containing six BRCT domains involved in transcription and in the cellular response to DNA damage. We show that PAXIP1 BRCT domains regulate WEE1-mediated phosphorylation of CDK1. Furthermore, ectopic expression of PAXIP1 promotes enhanced caspase-3-mediated apoptosis in cells treated with WEE1 inhibitor AZD1775 (formerly, MK-1775) and cisplatin compared with cells treated with AZD1775 alone. Cell lines and patient-derived xenograft models expressing both PAXIP1 and WEE1 exhibited synergistic effects of AZD1775 and cisplatin. In summary, PAXIP1 is involved in sensitizing lung cancer cells to the WEE1 inhibitor AZD1775 in combination with platinum-based treatment. We propose that WEE1 and PAXIP1 levels may be used as mechanism-based biomarkers of response when WEE1 inhibitor AZD1775 is combined with DNA-damaging agents. Mol Cancer Ther; 15(7); 1669-81. (c)2016 AACR. PMID- 27196767 TI - Cetuximab Resistance in Squamous Carcinomas of the Upper Aerodigestive Tract Is Driven by Receptor Tyrosine Kinase Plasticity: Potential for mAb Mixtures. AB - Squamous cell carcinomas (SCC) arising in upper parts of the aerodigestive tract are among the leading causes of death worldwide. EGFR has been found to play an essential role in driving the malignancy of SCC of the upper aerodigestive tract (SCCUAT), but, despite this, clinical results using a range of different EGFR targeted agents have been disappointing. Cetuximab is currently the only EGFR targeted agent approved by the FDA for treatment of SCCUAT. However, intrinsic and acquired cetuximab resistance is a major problem for effective therapy. Thus, a better understanding of the mechanisms responsible for cetuximab resistance is valuable for development of the next generation of antibody therapeutics. In order to better understand the underlying mechanisms of cetuximab resistance in SCCUAT, we established from cetuximab-sensitive models cell lines with acquired resistance to cetuximab by continuous selective pressure in vitro and in vivo Our results show that resistant clones maintain partial dependency on EGFR and that receptor tyrosine kinase plasticity mediated by HER3 and IGF1R plays an essential role. A multitarget mAb mixture against EGFR, HER3, and IGF1R was able to overcome cetuximab resistance in vitro To our surprise, these findings could be extended to include SCCUAT cell lines with intrinsic resistance to cetuximab, suggesting that the triad consisting of EGFR, HER3, and IGF1R plays a key role in SCCUAT. Our results thus provide a rationale for simultaneous targeting of EGFR, HER3, and IGF1R in SCCUAT. Mol Cancer Ther; 15(7); 1614-26. (c)2016 AACR. PMID- 27196768 TI - EGFR-Mediated Reactivation of MAPK Signaling Induces Acquired Resistance to GSK2118436 in BRAF V600E-Mutant NSCLC Cell Lines. AB - Although treatment of BRAF V600E-mutant non-small cell lung cancer (NSCLC(V600E)) with GSK2118436 has shown an encouraging efficacy, most patients develop resistance. To investigate the mechanisms of acquired resistance to GSK2118436 in NSCLC(V600E), we established GSK2118436-resistant (GSR) cells by exposing MV522 NSCLC(V600E) to increasing GSK2118436 concentrations. GSR cells displayed activated EGFR-RAS-CRAF signaling with upregulated EGFR ligands and sustained activation of ERK1/2, but not MEK1/2, in the presence of GSK2118436. Treatment of GSR cells with GSK2118436 enhanced EGFR-mediated RAS activity, leading to the formation of BRAF-CRAF dimers and transactivation of CRAF. Interestingly, sustained activation of ERK1/2 was partly dependent on receptor-interacting protein kinase-2 (RIP2) activity, but not on MEK1/2 activity. Combined BRAF and EGFR inhibition blocked reactivation of ERK signaling and improved efficacy in vitro and in vivo Our findings support the evaluation of combined BRAF and EGFR inhibition in NSCLC(V600E) with acquired resistance to BRAF inhibitors. Mol Cancer Ther; 15(7); 1627-36. (c)2016 AACR. PMID- 27196769 TI - Cell-Cycle Gene Alterations in 4,864 Tumors Analyzed by Next-Generation Sequencing: Implications for Targeted Therapeutics. AB - Alterations in the cyclin-dependent kinase (CDK)-retinoblastoma (RB) machinery disrupt cell-cycle regulation and are being targeted in drug development. To understand the cancer types impacted by this pathway, we analyzed frequency of abnormalities in key cell-cycle genes across 4,864 tumors using next-generation sequencing (182 or 236 genes; Clinical Laboratory Improvement Amendments laboratory). Aberrations in the cell-cycle pathway were identified in 39% of cancers, making this pathway one of the most commonly altered in cancer. The frequency of aberrations was as follows: CDKN2A/B (20.1% of all patients), RB1 (7.6%), CCND1 (6.1%), CCNE1 (3.6%), CDK4 (3.2%), CCND3 (1.8%), CCND2 (1.7%), and CDK6 (1.7%). Rates and types of aberrant cell-cycle pathway genes differed between cancer types and within histologies. Analysis of coexisting and mutually exclusive genetic aberrations showed that CCND1, CCND2, and CCND3 aberrations were all positively associated with CDK6 aberrations [OR and P values, multivariate analysis: CCND1 and CDK6 (OR = 3.5; P < 0.0001), CCND2 and CDK6 (OR = 4.3; P = 0.003), CCND3 and CDK6 (OR = 3.6; P = 0.007)]. In contrast, RB1 alterations were negatively associated with multiple gene anomalies in the cell cycle pathway, including CCND1 (OR = 0.25; P = 0.003), CKD4 (OR = 0.10; P = 0.001), and CDKN2A/B (OR = 0.21; P < 0.0001). In conclusion, aberrations in the cell-cycle pathway were very common in diverse cancers (39% of 4,864 neoplasms). The frequencies and types of alterations differed between and within tumor types and will be informative for drug development strategies. Mol Cancer Ther; 15(7); 1682-90. (c)2016 AACR. PMID- 27196770 TI - Inhibition of Nucleotide Synthesis Targets Brain Tumor Stem Cells in a Subset of Glioblastoma. AB - Inhibition of both the de novo (DNP) and salvage (NSP) pathways of nucleoside synthesis has been demonstrated to impair leukemia cells. We endeavored to determine whether this approach would be efficacious in glioblastoma. To diminish nucleoside biosynthesis, we utilized compound DI-39, which selectively targets NSP, in combination with thymidine (dT), which selectively targets DNP. We employed in vitro and ex vivo models to determine the effects of pretreatment with dT + DI-39 on brain tumor stem cells (BTSC). Here, we demonstrate that this combinatorial therapy elicits a differential response across a spectrum of human patient-derived glioblastoma cultures. As determined by apoptotic markers, most cultures were relatively resistant to treatment, although a subset was highly sensitive. Sensitivity was unrelated to S-phase delay and to DNA damage induced by treatment. Bioinformatics analysis indicated that response across cultures was associated with the transcription factor PAX3 (associated with resistance) and with canonical pathways, including the nucleotide excision repair pathway, PTEN (associated with resistance), PI3K/AKT (associated with sensitivity), and ErbB2 ErbB3. Our in vitro assays demonstrated that, in sensitive cultures, clonal sphere formation was reduced upon removal from pretreatment. In contrast, in a resistant culture, clonal sphere formation was slightly increased upon removal from pretreatment. Moreover, in an intracranial xenograft model, pretreatment of a sensitive culture caused significantly smaller and fewer tumors. In a resistant culture, tumors were equivalent irrespective of pretreatment. These results indicate that, in the subset of sensitive glioblastoma, BTSCs are targeted by inhibition of pyrimidine synthesis. Mol Cancer Ther; 15(6); 1271-8. (c)2016 AACR. PMID- 27196771 TI - Reduced Shedding of Surface Mesothelin Improves Efficacy of Mesothelin-Targeting Recombinant Immunotoxins. AB - Mesothelin (MSLN) is a differentiation antigen that is highly expressed in many epithelial cancers. MSLN is an important therapeutic target due to its high expression in cancers and limited expression in normal human tissues. Although it has been assumed that shed antigen is a barrier to immunotoxin action, a modeling study predicted that shed MSLN may enhance the action of MSLN-targeting recombinant immunotoxins such as SS1P and similar therapeutics by facilitating their redistribution within tumors. We aimed to determine whether shed MSLN enhances or reduces the antitumor effect of MSLN-targeting immunotoxins SS1P and RG7787. We engineered a cell line, A431/G9 (TACE mutant) that expresses a mutant form of MSLN in which the TNF-converting enzyme protease site is replaced with GGGS. We compared the response of the TACE-mutant cells with immunotoxins SS1P and RG7787 with that of the parental A431/H9 cell line. We show that TACE-mutant cells shed 80% less MSLN than A431/H9 cells, that TACE-mutant cells show a 2- to 3-fold increase in MSLN-targeted immunotoxin uptake, and that they are about 5 fold more sensitive to SS1P killing in cell culture. Tumors with reduced shedding respond significantly better to treatment with SS1P and RG7787. Our data show that MSLN shedding is an impediment to the antitumor activity of SS1P and RG7787. Approaches that decrease MSLN shedding could enhance the efficacy of immunotoxins and immunoconjugates targeting MSLN-expressing tumors. Mol Cancer Ther; 15(7); 1648-55. (c)2016 AACR. PMID- 27196772 TI - An Artificially Designed Interfering lncRNA Expressed by Oncolytic Adenovirus Competitively Consumes OncomiRs to Exert Antitumor Efficacy in Hepatocellular Carcinoma. AB - Endogenous miRNAs, especially oncogenic miRNAs (OncomiR), have been molecular targets for cancer therapy. We generated an artificially designed interfering long noncoding RNA (lncRNAi), which contains the sequences that can complementarily bind to multiple OncomiRs and is expressed by cancer-selectively replicating adenovirus. The adenovirus-expressed lncRNAi with high levels in hepatocellular carcinoma (HCC) cells competes with OncomiR target genes to bind to and consume OncomiRs, thereby achieving the targeted anti-HCC efficacy. With the targeting replication of adenovirus in HCC cells, lncRNAi was highly expressed and resulted in decreased abilities of proliferation, migration, and invasion, induced cell-cycle changes and apoptosis, and markedly changed the cellular mRNA and miRNA expression profiles in HCC cells. The optimal antitumor effect was also demonstrated on HCC cell line xenograft models and HCC patient derived xenograft (PDX) tumor models in nude mice. This strategy has established a technology platform with a reliable therapeutic effect for HCC therapy. Mol Cancer Ther; 15(7); 1436-51. (c)2016 AACR. PMID- 27196774 TI - Antagonists of IGF:Vitronectin Interactions Inhibit IGF-I-Induced Breast Cancer Cell Functions. AB - We provide proof-of-concept evidence for a new class of therapeutics that target growth factor:extracellular matrix (GF:ECM) interactions for the management of breast cancer. Insulin-like growth factor-I (IGF-I) forms multiprotein complexes with IGF-binding proteins (IGFBP) and the ECM protein vitronectin (VN), and stimulates the survival, migration and invasion of breast cancer cells. For the first time we provide physical evidence for IGFBP-3:VN interactions in breast cancer patient tissues; these interactions were predominantly localized to tumor cell clusters and in stroma surrounding tumor cells. We show that disruption of IGF-I:IGFBP:VN complexes with L(27)-IGF-II inhibits IGF-I:IGFBP:VN-stimulated breast cancer cell migration and proliferation in two- and three-dimensional assay systems. Peptide arrays screened to identify regions critical for the IGFBP 3/-5:VN and IGF-II:VN interactions demonstrated IGFBP-3/-5 and IGF-II binds VN through the hemopexin-2 domain, and VN binds IGFBP-3 at residues not involved in the binding of IGF-I to IGFBP-3. IGFBP-interacting VN peptides identified from these peptide arrays disrupted the IGF-I:IGFBP:VN complex, impeded the growth of primary tumor-like spheroids and, more importantly, inhibited the invasion of metastatic breast cancer cells in 3D assay systems. These studies provide first in-field evidence for the utility of small peptides in antagonizing GF:ECM mediated biologic functions and present data demonstrating the potential of these peptide antagonists as novel therapeutics. Mol Cancer Ther; 15(7); 1602-13. (c)2016 AACR. PMID- 27196773 TI - Emodin Inhibits Breast Cancer Growth by Blocking the Tumor-Promoting Feedforward Loop between Cancer Cells and Macrophages. AB - Macrophage infiltration correlates with severity in many types of cancer. Tumor cells recruit macrophages and educate them to adopt an M2-like phenotype through the secretion of chemokines and growth factors, such as MCP1 and CSF1. Macrophages in turn promote tumor growth through supporting angiogenesis, suppressing antitumor immunity, modulating extracellular matrix remodeling, and promoting tumor cell migration. Thus, tumor cells and macrophages interact to create a feedforward loop supporting tumor growth and metastasis. In this study, we tested the ability of emodin, a Chinese herb-derived compound, to inhibit breast cancer growth in mice and examined the underlying mechanisms. Emodin was used to treat mice bearing EO771 or 4T1 breast tumors. It was shown that emodin attenuated tumor growth by inhibiting macrophage infiltration and M2-like polarization, accompanied by increased T-cell activation and reduced angiogenesis in tumors. The tumor inhibitory effects of emodin were lost in tumor-bearing mice with macrophage depletion. Emodin inhibited IRF4, STAT6, and C/EBPbeta signaling and increased inhibitory histone H3 lysine 27 tri-methylation (H3K27m3) on the promoters of M2-related genes in tumor-associated macrophages. In addition, emodin inhibited tumor cell secretion of MCP1 and CSF1, as well as expression of surface anchoring molecule Thy-1, thus suppressing macrophage migration toward and adhesion to tumor cells. These results suggest that emodin acts on both breast cancer cells and macrophages and effectively blocks the tumor-promoting feedforward loop between the two cell types, thereby inhibiting breast cancer growth and metastasis. Mol Cancer Ther; 15(8); 1931-42. (c)2016 AACR. PMID- 27196775 TI - A Novel Glycogen Synthase Kinase-3 Inhibitor Optimized for Acute Myeloid Leukemia Differentiation Activity. AB - Standard therapies used for the treatment of acute myeloid leukemia (AML) are cytotoxic agents that target rapidly proliferating cells. Unfortunately, this therapeutic approach has limited efficacy and significant toxicity and the majority of AML patients still die of their disease. In contrast to the poor prognosis of most AML patients, most individuals with a rare subtype of AML, acute promyelocytic leukemia, can be cured by differentiation therapy using regimens containing all-trans retinoic acid. GSK3 has been previously identified as a therapeutic target in AML where its inhibition can lead to the differentiation and growth arrest of leukemic cells. Unfortunately, existing GSK3 inhibitors lead to suboptimal differentiation activity making them less useful as clinical AML differentiation agents. Here, we describe the discovery of a novel GSK3 inhibitor, GS87. GS87 was discovered in efforts to optimize GSK3 inhibition for AML differentiation activity. Despite GS87's dramatic ability to induce AML differentiation, kinase profiling reveals its high specificity in targeting GSK3 as compared with other kinases. GS87 demonstrates high efficacy in a mouse AML model system and unlike current AML therapeutics, exhibits little effect on normal bone marrow cells. GS87 induces potent differentiation by more effectively activating GSK3-dependent signaling components including MAPK signaling as compared with other GSK3 inhibitors. GS87 is a novel GSK3 inhibitor with therapeutic potential as a differentiation agent for non-promyelocytic AML. Mol Cancer Ther; 15(7); 1485-94. (c)2016 AACR. PMID- 27196776 TI - Secretory TRAIL-Armed Natural Killer Cell-Based Therapy: In Vitro and In Vivo Colorectal Peritoneal Carcinomatosis Xenograft. AB - Since its discovery in 1995, TNF-related apoptosis-inducing ligand (TRAIL) has sparked growing interest among oncologists due to its remarkable ability to induce apoptosis in malignant human cells, but not in most normal cells. However, one major drawback is its fast clearance rate in vivo Thus, the development of an alternative means of delivery may increase the effectiveness of TRAIL-based therapy. In this study, we developed a secretory TRAIL-armed natural killer (NK) cell-based therapy and assessed its cytotoxic effects on colorectal cancer cells and its tumoricidal efficacy on colorectal peritoneal carcinomatosis xenograft. We generated genetically modified NK cells by transduction with a lentiviral vector consisting of a secretion signal domain, a trimerization domain, and an extracellular domain of the TRAIL gene. These NK cells secreted a glycosylated form of TRAIL fusion protein that induced apoptotic death. Intraperitoneally, but not intravenously, injected NK cells effectively accumulated at tumor sites, infiltrated tumor tissue, induced apoptosis, and delayed tumor growth. These results shed light on the therapeutic potential of genetically engineered NK cells to treat peritoneal carcinomatosis. Mol Cancer Ther; 15(7); 1591-601. (c)2016 AACR. PMID- 27196778 TI - Genomic and Immunological Tumor Profiling Identifies Targetable Pathways and Extensive CD8+/PDL1+ Immune Infiltration in Inflammatory Breast Cancer Tumors. AB - Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer that remains poorly understood at the molecular level. Comprehensive tumor profiling was performed to understand clinically actionable alterations in IBC. Targeted next-generation sequencing (NGS) and IHC were performed to identify activated pathways in IBC tumor tissues. siRNA studies examined the impact of IBC genomic variants in cellular models. IBC tumor tissues were further characterized for immune infiltration and immune checkpoint expression by IHC. Genomic analysis identified recurrent alterations in core biologic pathways, including activating and targetable variants in HER/PI3K/mTOR signaling. High rates of activating HER3 point mutations were discovered in IBC tumors. Cell line studies confirmed a role for mutant HER3 in IBC cell proliferation. Immunologic analysis revealed a subset of IBC tumors associated with high CD8(+)/PD-L1(+) lymphocyte infiltration. Immune infiltration positively correlated with an NGS-based estimate of neoantigen exposure derived from the somatic mutation rate and mutant allele frequency, iScore. Additionally, DNA mismatch repair alterations, which may contribute to higher iScores, occurred at greater frequency in tumors with higher immune infiltration. Our study identifies genomic alterations that mechanistically contribute to oncogenic signaling in IBC and provides a genetic basis for the selection of clinically relevant targeted and combination therapeutic strategies. Furthermore, an NGS-based estimate of neoantigen exposure developed in this study (iScore) may be a useful biomarker to predict immune infiltration in IBC and other cancers. The iScore may be associated with greater levels of response to immunotherapies, such as PD-L1/PD-1-targeted therapies. Mol Cancer Ther; 15(7); 1746-56. (c)2016 AACR. PMID- 27196779 TI - Dual Carfilzomib and Doxorubicin-Loaded Liposomal Nanoparticles for Synergistic Efficacy in Multiple Myeloma. AB - Here, we report the synthesis and evaluation of dual drug-loaded nanoparticles as an effective means to deliver carfilzomib and doxorubicin to multiple myeloma tumor cells at their optimal synergistic ratio. First, various molar ratios of carfilzomib to doxorubicin were screened against multiple myeloma cell lines to determine the molar ratio that elicited the greatest synergy using the Chou Talalay method. The therapeutic agents were then incorporated into liposomes at the optimal synergistic ratio of 1:1 to yield dual drug-loaded nanoparticles with a narrow size range of 115 nm and high reproducibility. Our results demonstrated that the dual drug-loaded liposomes exhibited synergy in vitro and were more efficacious in inhibiting tumor growth in vivo than a combination of free drugs, while at the same time reducing systemic toxicity. Taken together, this study presents the synthesis and preclinical evaluation of dual drug-loaded liposomes containing carfilzomib and doxorubicin for enhanced therapeutic efficacy to improve patient outcome in multiple myeloma. Mol Cancer Ther; 15(7); 1452-9. (c)2016 AACR. PMID- 27196777 TI - NQO1-Mediated Tumor-Selective Lethality and Radiosensitization for Head and Neck Cancer. AB - Ionizing radiation (IR) is a key therapeutic regimen for many head and neck cancers (HNC). However, the 5-year overall survival rate for locally advanced HNCs is approximately 50% and better therapeutic efficacy is needed. NAD(P)H: quinone oxidoreductase 1 (NQO1) is overexpressed in many cancers, and beta lapachone (beta-lap), a unique NQO1 bioactivatable drug, exploits this enzyme to release massive reactive oxygen species (ROS) that synergize with IR to kill by programmed necrosis. beta-Lap represents a novel therapeutic opportunity in HNC leading to tumor-selective lethality that will enhance the efficacy of IR. Immunohistochemical staining and Western blot assays were used to assess the expression levels of NQO1 in HNC cells and tumors. Forty-five percent of endogenous HNCs expressed elevated NQO1 levels. In addition, multiple HNC cell lines and tumors demonstrated elevated levels of NQO1 expression and activity and were tested for anticancer lethality and radiosensitization by beta-lap using long-term survival assays. The combination of nontoxic beta-lap doses and IR significantly enhanced NQO1-dependent tumor cell lethality, increased ROS, TUNEL positive cells, DNA damage, NAD(+), and ATP consumption, and resulted in significant antitumor efficacy and prolonged survival in two xenograft murine HNC models, demonstrating beta-lap radiosensitization of HNCs through a NQO1 dependent mechanism. This translational study offers a potential biomarker-driven strategy using NQO1 expression to select tumors susceptible to beta-lap-induced radiosensitization. Mol Cancer Ther; 15(7); 1757-67. (c)2016 AACR. PMID- 27196781 TI - PIM Kinase Inhibitors Kill Hypoxic Tumor Cells by Reducing Nrf2 Signaling and Increasing Reactive Oxygen Species. AB - Intratumoral hypoxia is a significant obstacle to the successful treatment of solid tumors, and it is highly correlated with metastasis, therapeutic resistance, and disease recurrence in cancer patients. As a result, there is an urgent need to develop effective therapies that target hypoxic cells within the tumor microenvironment. The Proviral Integration site for Moloney murine leukemia virus (PIM) kinases represent a prosurvival pathway that is upregulated in response to hypoxia, in a HIF-1-independent manner. We demonstrate that pharmacologic or genetic inhibition of PIM kinases is significantly more toxic toward cancer cells in hypoxia as compared with normoxia. Xenograft studies confirm that PIM kinase inhibitors impede tumor growth and selectively kill hypoxic tumor cells in vivo Experiments show that PIM kinases enhance the ability of tumor cells to adapt to hypoxia-induced oxidative stress by increasing the nuclear localization and activity of nuclear factor-erythroid 2 p45-related factor 2 (Nrf2), which functions to increase the expression of antioxidant genes. Small molecule PIM kinase inhibitors prevent Nrf2 from accumulating in the nucleus, reducing the transcription of cytoprotective genes and leading to the build-up of intracellular reactive oxygen species (ROS) to toxic levels in hypoxic tumor cells. This toxic effect of PIM inhibitors can be successfully blocked by ROS scavengers, including N-acetyl cystine and superoxide dismutase. Thus, inhibition of PIM kinases has the potential to oppose hypoxia-mediated therapeutic resistance and induce cell death in the hypoxic tumor microenvironment. Mol Cancer Ther; 15(7); 1637-47. (c)2016 AACR. PMID- 27196780 TI - Dual mTORC1/2 Inhibition as a Novel Strategy for the Resensitization and Treatment of Platinum-Resistant Ovarian Cancer. AB - There is considerable interest in the clinical development of inhibitors of mTOR complexes mTORC1 and 2. Because mTORC1 and its downstream mRNA translation effectors may protect against genotoxic DNA damage, we investigated the inhibition of mTORC1 and mTORC1/2 in the ability to reverse platinum resistance in tissue culture and in animal tumor models of serous ovarian cancer. Cell survival, tumor growth, PI3K-AKT-mTOR pathway signaling, DNA damage and repair response (DDR) gene expression, and translational control were all investigated. We show that platinum-resistant OVCAR-3 ovarian cancer cells are resensitized to low levels of carboplatin in culture by mTOR inhibition, demonstrating reduced survival after treatment with either mTORC1 inhibitor everolimus or mTORC1/2 inhibitor PP242. Platinum resistance is shown to be associated with activating phosphorylation of AKT and CHK1, inactivating phosphorylation of 4E-BP1, the negative regulator of eIF4E, which promotes increased cap-dependent mRNA translation and increased levels of CHK1 and BRCA1 proteins. Animals with platinum-resistant OVCAR-3 tumors treated with carboplatin plus mTORC1/2 inhibition had significantly longer median survival and strikingly reduced metastasis compared with animals treated with carboplatin plus everolimus, which inhibits only mTORC1. Reduced tumor growth, metastasis, and increased survival by mTORC1/2 inhibition with carboplatin treatment was associated with reduced AKT activating phosphorylation and increased 4E-BP1 hypophosphorylation (activation). We conclude that mTORC1/2 inhibition is superior to mTORC1 inhibition in reversing platinum resistance in tumors and strongly impairs AKT activation, DNA repair responses, and translation, promoting improved survival in the background of platinum resistance. Mol Cancer Ther; 15(7); 1557-67. (c)2016 AACR. PMID- 27196782 TI - In Vitro and In Vivo Activity of AMG 337, a Potent and Selective MET Kinase Inhibitor, in MET-Dependent Cancer Models. AB - The MET receptor tyrosine kinase is involved in cell growth, survival, and invasion. Clinical studies with small molecule MET inhibitors have shown the role of biomarkers in identifying patients most likely to benefit from MET-targeted therapy. AMG 337 is an oral, small molecule, ATP-competitive, highly selective inhibitor of the MET receptor. Herein, we describe AMG 337 preclinical activity and mechanism of action in MET-dependent tumor models. These studies suggest MET is the only therapeutic target for AMG 337. In an unbiased tumor cell line proliferation screen (260 cell lines), a closely related analogue of AMG 337, Compound 5, exhibited activity in 2 of 260 cell lines; both were MET-amplified. Additional studies examining the effects of AMG 337 on the proliferation of a limited panel of cell lines with varying MET copy numbers revealed that high level focal MET amplification (>12 copies) was required to confer MET oncogene addiction and AMG 337 sensitivity. One MET-amplified cell line, H1573 (>12 copies), was AMG 337 insensitive, possibly because of a downstream G12A KRAS mutation. Mechanism-of-action studies in sensitive MET-amplified cell lines demonstrated that AMG 337 inhibited MET and adaptor protein Gab-1 phosphorylation, subsequently blocking the downstream PI3K and MAPK pathways. AMG 337 exhibited potency in pharmacodynamic assays evaluating MET signaling in tumor xenograft models; >90% inhibition of Gab-1 phosphorylation was observed at 0.75 mg/kg. These findings describe the preclinical activity and mechanism of action of AMG 337 in MET-dependent tumor models and indicate its potential as a novel therapeutic for the treatment of MET-dependent tumors. Mol Cancer Ther; 15(7); 1568-79. (c)2016 AACR. PMID- 27196785 TI - Children's perceptions of smile esthetics and their influence on social judgment. AB - OBJECTIVE: To define a threshold of acceptance of smile esthetics for children and adolescents. MATERIALS AND METHODS: A systematic search in the medical literature (PubMed, PubMed Central, National Library of Medicine's Medline, Embase, Cochrane Central Register of Controlled Clinical Trials, Web of Knowledge, Scopus, Google Scholar, and LILACs) was performed to identify all peer reviewed papers reporting data regarding the evaluation of children's and adolescents' perceptions of dental esthetic factors. The search was conducted using a research strategy based on keywords such as "children," "adolescents," "smile aesthetics perception," "smile aesthetics evaluation." Studies analyzing smile esthetics involving at least 10 observers younger than 18 years of age were selected. RESULTS: Among the 1667 analyzed articles, five studies were selected for the final review process. No study included in the review analyzed perception of smile anomalies in a quantitative or qualitative way, thus no threshold was identified for smile features. Among the analyzed samples, unaltered smiles were always significantly associated with better evaluation scores when compared with altered smiles. CONCLUSIONS: Smile esthetics influence social perception during childhood and adolescence. However, thresholds of smile esthetic acceptance in children and adolescents are still not available. PMID- 27196783 TI - Apratoxin A Shows Novel Pancreas-Targeting Activity through the Binding of Sec 61. AB - Apratoxin A is a natural product with potent antiproliferative activity against many human cancer cell lines. However, we and other investigators observed that it has a narrow therapeutic window in vivo Previous mechanistic studies have suggested its involvement in the secretory pathway as well as the process of chaperone-mediated autophagy. Still the link between the biologic activities of apratoxin A and its in vivo toxicity has remained largely unknown. A better understanding of this relationship is critically important for any further development of apratoxin A as an anticancer drug. Here, we describe a detailed pathologic analysis that revealed a specific pancreas-targeting activity of apratoxin A, such that severe pancreatic atrophy was observed in apratoxin A treated animals. Follow-up tissue distribution studies further uncovered a unique drug distribution profile for apratoxin A, showing high drug exposure in pancreas and salivary gland. It has been shown previously that apratoxin A inhibits the protein secretory pathway by preventing cotranslational translocation. However, the molecule targeted by apratoxin A in this pathway has not been well defined. By using a (3)H-labeled apratoxin A probe and specific Sec 61alpha/beta antibodies, we identified that the Sec 61 complex is the molecular target of apratoxin A. We conclude that apratoxin A in vivo toxicity is likely caused by pancreas atrophy due to high apratoxin A exposure. Mol Cancer Ther; 15(6); 1208 16. (c)2016 AACR. PMID- 27196786 TI - Enhanced amplified spontaneous emission in a quantum dot-doped polymer-dispersed liquid crystal. AB - Quantum dot-doped polymer-dispersed liquid crystals (QD-PDLCs) were prepared by photoinitiated polymerization and sealed in capillary tubes. The concentration of QDs in the PDLC was 1 wt%. Amplified spontaneous emission (ASE) of the quantum dot-doped polymer-dispersed liquid crystals was observed with 532 nm wavelength laser excitation. The threshold for ASE was 6 mJ cm(-2), which is much lower than that for homogeneous quantum dot-doped polymer (25 mJ cm(-2)). The threshold for ASE was dramatically enhanced when the working temperature exceeded the clearing point of the liquid crystal; this result demonstrates that multi-scattering caused by the liquid crystals effectively improved the path length or dwell time of light in the gain region, which played a key role in decreasing the threshold for ASE. PMID- 27196784 TI - Quantitative Phosphoproteomics Reveals Wee1 Kinase as a Therapeutic Target in a Model of Proneural Glioblastoma. AB - Glioblastoma (GBM) is the most common malignant primary brain cancer. With a median survival of about a year, new approaches to treating this disease are necessary. To identify signaling molecules regulating GBM progression in a genetically engineered murine model of proneural GBM, we quantified phosphotyrosine-mediated signaling using mass spectrometry. Oncogenic signals, including phosphorylated ERK MAPK, PI3K, and PDGFR, were found to be increased in the murine tumors relative to brain. Phosphorylation of CDK1 pY15, associated with the G2 arrest checkpoint, was identified as the most differentially phosphorylated site, with a 14-fold increase in phosphorylation in the tumors. To assess the role of this checkpoint as a potential therapeutic target, syngeneic primary cell lines derived from these tumors were treated with MK-1775, an inhibitor of Wee1, the kinase responsible for CDK1 Y15 phosphorylation. MK-1775 treatment led to mitotic catastrophe, as defined by increased DNA damage and cell death by apoptosis. To assess the extensibility of targeting Wee1/CDK1 in GBM, patient-derived xenograft (PDX) cell lines were also treated with MK-1775. Although the response was more heterogeneous, on-target Wee1 inhibition led to decreased CDK1 Y15 phosphorylation and increased DNA damage and apoptosis in each line. These results were also validated in vivo, where single-agent MK-1775 demonstrated an antitumor effect on a flank PDX tumor model, increasing mouse survival by 1.74-fold. This study highlights the ability of unbiased quantitative phosphoproteomics to reveal therapeutic targets in tumor models, and the potential for Wee1 inhibition as a treatment approach in preclinical models of GBM. Mol Cancer Ther; 15(6); 1332-43. (c)2016 AACR. PMID- 27196787 TI - An examination of the default mode network in individuals with autonomous sensory meridian response (ASMR). AB - Autonomous Sensory Meridian Response (ASMR) is a perceptual condition in which specific visual and auditory stimuli consistently trigger tingling sensations on the scalp and neck, sometimes spreading to the back and limbs. These triggering stimuli are often social, almost intimate, in nature (e.g., hearing whispering, or watching someone brush her hair), and often elicit a calm and positive emotional state. Surprisingly, despite its prevalence in the general population, no published study has examined the neural underpinnings of ASMR. In the current study, the default mode network (DMN) of 11 individuals with ASMR was contrasted to that of 11 matched controls. The results indicated that the DMN of individuals with ASMR showed significantly less functional connectivity than that of controls. The DMN of individuals with ASMR also demonstrated increased connectivity between regions in the occipital, frontal, and temporal cortices, suggesting that ASMR was associated with a blending of multiple resting-state networks. This atypical functional connectivity likely influences the unique sensory-emotional experiences associated with ASMR. PMID- 27196788 TI - A statistical approach to determining responses to individual peptides from pooled-peptide ELISpot data. AB - To investigate in detail the effect of infection or vaccination on the human immune system, ELISpot assays are used to simultaneously test the immune response to a large number of peptides of interest. Scientists commonly use "peptide pools", where, instead of an individual peptide, a test well contains a group of peptides. Since the response from a well may be due to any or many of the peptides in the pool, pooled assays usually need to be followed by confirmatory assays of a number of individual peptides. We present a statistical method that enables estimation of individual peptide responses from pool responses using the Expectation Maximization (EM) algorithm for "incomplete data". We demonstrate the accuracy and precision of these estimates in simulation studies of ELISpot plates with 90 pools of 6 or 7 peptides arranged in three dimensions and three Mock wells for the estimation of background. In analysis of real pooled data from 6 subjects in a HIV-1 vaccine trial, where 199 peptides were arranged in 80 pools if size 9 or 10, our estimates were in very good agreement with the results from individual-peptide confirmatory assays. Compared to the classical approach, we could identify almost all the same peptides with high or moderate response, with less than half the number of confirmatory tests. Our method facilitates efficient use of the information available in pooled ELISpot data to avoid or reduce the need for confirmatory testing. We provide an easy-to-use free online application for implementing the method, where on uploading two spreadsheets with the pool design and pool responses, the user obtains the estimates of the individual peptide responses. PMID- 27196790 TI - The influence of bilingualism on the preference for the mouth region of dynamic faces. AB - Bilingual infants show an extended period of looking at the mouth of talking faces, which provides them with additional articulatory cues that can be used to boost the challenging situation of learning two languages (Pons, Bosch & Lewkowicz, 2015). However, the eye region also provides fundamental cues for emotion perception and recognition, as well as communication. Here, we explored whether the adaptations resulting from learning two languages are specific to linguistic content or if they also influence the focus of attention when looking at dynamic faces. We recorded the eye gaze of bilingual and monolingual infants (8- and 12-month-olds) while watching videos of infants and adults portraying different emotional states (neutral, crying, and laughing). When looking at infant faces, bilinguals looked longer at the mouth region as compared to monolinguals regardless of age. However, when presented with adult faces, 8-month old bilingual infants looked longer at the mouth region and less at the eye region compared to 8-month-old monolingual infants, but no effect of language exposure was found at 12 months of age. These findings suggest that the bias to the mouth region in bilingual infants at 8 months of age can be generalized to other audiovisual dynamic faces that do not contain linguistic information. We discuss the potential implications of such bias in early social and communicative development. PMID- 27196789 TI - Human immunophenotyping via low-variance, low-bias, interpretive regression modeling of small, wide data sets: Application to aging and immune response to influenza vaccination. AB - Small, wide data sets are commonplace in human immunophenotyping research. As defined here, a small, wide data set is constructed by sampling a small to modest quantity n,1100-fold), rapidly, and reversibly activated by cooling by only a few degrees. We found that the mechanism(s) underlying PLCgamma2 PLAID mutant activation by cool temperatures is distinct from a mere loss of SH-region-mediated autoinhibition and dependent on both the integrity and the pliability of the spPH domain. The results suggest a new mechanism of PLCgamma activation with unique thermodynamic features and assign a novel regulatory role to its spPH domain. Involvement of this mechanism in other human disease states associated with cooling such as exertional asthma and certain acute coronary events appears an intriguing possibility. PMID- 27196804 TI - Mapping Geographic Variation in Infant Mortality and Related Black-White Disparities in the US. AB - BACKGROUND: In the US, black infants remain more than twice as likely as white infants to die in the first year of life. Previous studies of geographic variation in infant mortality disparities have been limited to large metropolitan areas where stable estimates of infant mortality rates by race can be determined, leaving much of the US unexplored. METHODS: The objective of this analysis was to describe geographic variation in county-level racial disparities in infant mortality rates across the 48 contiguous US states and District of Columbia using national linked birth and infant death period files (2004-2011). We implemented Bayesian shared component models in OpenBUGS, borrowing strength across both spatial units and racial groups. We mapped posterior estimates of mortality rates for black and white infants as well as relative and absolute disparities. RESULTS: Black infants had higher infant mortality rates than white infants in all counties, but there was geographic variation in the magnitude of both relative and absolute disparities. The mean difference between black and white rates was 5.9 per 1,000 (median: 5.8, interquartile range: 5.2 to 6.6 per 1,000), while those for black infants were 2.2 times higher than for white infants (median: 2.1, interquartile range: 1.9-2.3). One quarter of the county-level variation in rates for black infants was shared with white infants. CONCLUSIONS: Examining county-level variation in infant mortality rates among black and white infants and related racial disparities may inform efforts to redress inequities and reduce the burden of infant mortality in the US. PMID- 27196805 TI - Racial/Ethnic Differences in the Role of Childhood Adversities for Mental Disorders Among a Nationally Representative Sample of Adolescents. AB - BACKGROUND: Childhood adversities may play a key role in the onset of mental disorders and influence patterns by race/ethnicity. We examined the relations between childhood adversities and mental disorders by race/ethnicity in the National Comorbidity Survey-Adolescent Supplement. METHODS: Using targeted maximum likelihood estimation, a rigorous and flexible estimation procedure, we estimated the relationship of each adversity with mental disorders (behavior, distress, fear, and substance use), and estimated the distribution of disorders by race/ethnicity in the absence of adversities. Targeted maximum likelihood estimation addresses the challenge of a multidimensional exposure such as a set of adversities because it facilitates "learning" from the data the strength of the relationships between each adversity and outcome, incorporating any interactions or nonlinearity, specific to each racial/ethnic group. Cross validation is used to select the best model without over fitting. RESULTS: Among adversities, physical abuse, emotional abuse, and sexual abuse had the strongest associations with mental disorders. Of all outcomes, behavior disorders were most strongly associated with adversities. Our comparisons of observed prevalences of mental disorders to estimates in the absence of adversities suggest lower prevalences of behavior disorders across all racial/ethnic groups. Estimates for distress disorders and substance use disorders varied in magnitude among groups, but some estimates were imprecise. Interestingly, results suggest that the adversities examined here do not play a major role in patterns of racial/ethnic differences in mental disorders. CONCLUSIONS: Although causal interpretation relies on assumptions, growing work on this topic suggests childhood adversities play an important role in mental disorder development in adolescents. PMID- 27196806 TI - Soy-based Infant Formula Feeding and Heavy Menstrual Bleeding Among Young African American Women. AB - BACKGROUND: Phytoestrogen exposure from soy formula feeding during infancy may disrupt reproductive system development, resulting in altered menstrual bleeding in adulthood. METHODS: We investigated this relationship in a cohort of 1,696 young African American women using enrollment data from the Study of Environment, Lifestyle, & Fibroids (2010-2012). Questionnaire data on soy formula feeding were available for 1,553 participants, 89% based on mother's report. Menstrual bleeding outcomes including those indicative of heavy menstrual bleeding were ascertained by interview. We estimated relative risks (RRs) and 95% confidence intervals (CI) for associations between soy formula feeding and menstrual bleeding outcomes using log-binomial regression and log-multinomial regression, comparing participants ever fed and never fed soy formula. RESULTS: We observed associations between soy formula feeding and variables indicating a history of heavy menstrual bleeding, including ever experiencing heavy, gushing-type bleeding (RR: 1.2, 95% CI: 1.0, 1.4), ever use of nonsteroidal anti-inflammatory drugs for heavy bleeding (RR: 1.3, 95% CI: 1.0, 1.6), and ever use of a contraceptive method for heavy bleeding (RR: 1.2, 95% CI, 0.9, 1.6). Among the subset of participants with menses in the past year who did not use medication that may alter menstrual flow (n = 762), our data suggested that soy formula feeding was associated with heavier flow and the adverse impact of menstrual bleeding on quality of life, but CIs were wide. CONCLUSIONS: Our data suggested that soy formula feeding is associated with heavy menstrual bleeding. Our results support the idea that infancy is a susceptible developmental window for female reproductive function. PMID- 27196808 TI - Long-Term Intra-Aortic Balloon Pump Support as Bridge to Left Ventricular Assist Device Implantation. AB - BACKGROUND: The intra-aortic balloon pump (IABP) can be used to bridge critically ill end-stage heart failure patients to left ventricular assist device (LVAD) implantation. However, the IABP's potential association with hemorrhagic complications raises concerns regarding its utilization in these patients. AIM: We investigated whether preoperative long-term IABP support increases hemorrhagic complications post-LVAD implantation. METHODS: Ten patients undergoing IABP support prior to LVAD implantation (IABP-LVAD group) were compared with 16 who did not require IABP support (LVAD group). RESULTS: Mean duration of IABP support was 25.8 days. Preoperatively, both groups were comparable in all measured parameters and indices of end-organ function. Perioperative (defined as three weeks post-LVAD implantation, including the procedure) cellular and noncellular blood transfusion requirements were similar between IABP-LVAD and LVAD groups (19.8 +/- 9.95 vs. 19.76 +/- 29.69 RBC units, p = 0.96; 3.8 +/- 4.14 vs. 2.0 +/- 6.44 plateletpheresis units p = 0.84; 23 +/- 16.04 vs. 25.14 +/- 37.8 fresh frozen plasma units, p = 0.45). Perioperative minimum hematocrit (33.6 +/- 5.6 vs. 36.59 +/- 4.8, p = 0.38) and minimum platelet count (199 +/- 153 vs. 144 +/- 65, p = 0.52) were similar in the two groups. Two patients in the IABP-LVAD group and three patients in the LVAD group underwent reoperation post-LVAD implantation for bleeding. Length of ICU stay was longer in the LVAD group but did not reach statistical significance (6.2 +/- 6.22 days in the IABP-LVAD group versus 13.45 +/- 10.95 days in the LVAD group, p = 0.06). CONCLUSIONS: Long-term IABP support as a bridge to LVAD implantation is not associated with increased hemorrhagic complications post-LVAD implantation. doi: 10.1111/jocs.12759 (J Card Surg 2016;31:467-471). PMID- 27196807 TI - Adropin as a potential marker of enzyme-positive acute coronary syndrome. AB - AIM: Enzyme-positive acute coronary syndrome (EPACS) can cause injury to or death of the heart muscle owing to prolonged ischaemia. Recent research has indicated that in addition to liver and brain cells, cardiomyocytes also produce adropin. We hypothesised that adropin is released into the bloodstream during myocardial injury caused by acute coronary syndrome (ACS), so serum and saliva levels rise as the myocytes die. Therefore, it could be useful to investigate how ACS affects the timing and significance of adropin release in human subjects. METHODS: Samples were taken over three days after admission, from 22 EPACS patients and 24 age- and gendermatched controls. The three major salivary glands (submandibular, sublingual and parotid) were immunohistochemically screened for adropin production, and serum and saliva adropin levels were measured by an enzyme-linked immunosorbent assay (ELISA). Salivary gland cells produce and secrete adropin locally. RESULTS: Serum adropin, troponin I, CK and CK-MB concentrations in the EPACS group became gradually higher than those in the control group up to six hours (p < 0.05), and troponin I continued to rise up to 12 hours after EPACS. The same relative increase in adropin level was observed in the saliva. Troponin I, CK and CK-MB levels started to decrease after 12 hours, while saliva and serum adropin levels started to decrease at six hours after EPACS. In samples taken four hours after EPACS, when the serum adropin value averaged 4.43 ng/ml, the receiver operating characteristic curve showed that the serum adropin concentration indicated EPACS with 91.7% sensitivity and 50% specificity, while when the cut-off adropin value in saliva was 4.12 ng/ml, the saliva adropin concentration indicated EPACS with 91.7% sensitivity and 57% specificity. CONCLUSION: In addition to cardiac troponin and CK-MB assays, measurement of adropin level in saliva and serum samples is a potential marker for diagnosing EPACS. PMID- 27196810 TI - Application of nanostructured drug delivery systems in immunotherapy of cancer: a review. AB - The cancer immunotherapy method uses the specificity of the immune system to provide a more effective than more conventional treatments, such as chemotherapy and radiotherapy. Immunotherapy has two main strategies (passive or active) to organize the immune system. Passive strategies use advantage of tumor hyperpermeable cells, which have enhanced permeability and retention effects. Nanoparticles due to their better accumulation within tissues and cells of the immune system are well suitable for delivery of immune therapies such as vaccines or adjuvants. In this review, we explained application of nanotechnology in immunotherapy of cancer. PMID- 27196809 TI - Assessing Callous-Unemotional Traits in Adolescents: Determining Cutoff Scores for the Inventory of Callous and Unemotional Traits. AB - OBJECTIVE: This study aims to establish a cut score for the Inventory of Callous Unemotional Traits, a well-validated measure of callous-unemotional (CU) traits in youth for which there is currently no cutoff score. METHOD: We analyzed data on 634 adolescents from high schools (n = 343) and juvenile detention centers (n = 291). Participants, their parents and guardians, and their teachers and staff members reported on participants' CU traits and aggressive/violent behavior. RESULTS: All three reports of CU traits as well as intersource composites were associated with aggression, violence, and detained status. Parent report was a better indicator compared to self-reports and teacher reports. Appropriate cut scores based on each report and composite were determined. CONCLUSION: We recommend that information from all available informants should be used whenever possible, but when only one informant report is feasible, parent reports are preferable. PMID- 27196811 TI - Structural Characteristics of Homogeneous Hydrophobic Ionic Liquid-HNO3-H2O Ternary System: Experimental Studies and Molecular Dynamics Simulations. AB - The solubility of water in the hydrophobic ionic liquid 1-ethyl-3 methylimidazolium bis(trifluoromethylsulfonyl)imide ([C2mim][NTf2]) increases significantly in the presence of HNO3. [C2mim][NTf2] is completely miscible with HNO3 but immiscible with water. The triangular phase diagram of the ternary system [C2mim][NTf2]-HNO3-H2O was determined at 300.1 K. The homogeneous [C2mim][NTf2]-HNO3-H2O phase is thermodynamically stable, while it can be separated into two phases with an increase of water content. Experiments (electrospray ionization mass spectrometry, Fourier transform infrared spectrometry, and (1)H-nuclear magnetic resonance spectrometry) and molecular dynamics simulations were carried out to investigate the interaction between [C2mim][NTf2], HNO3, and water in the homogeneous phase. It was found that NO3(-) ions interact with both C2mim(+) and water via H-bonding and act as a "bridge" to induce a large amount of water to be dissolved in the hydrophobic IL phase. This confirms that the complexes [C2mim-NTf2-C2mim](+) and [NTf2-C2mim-NTf2](-) exist in the homogeneous [C2mim][NTf2]-HNO3-H2O system at the concentration of HNO3 up to 27.01 wt % and of water as high as 20.74 wt %. PMID- 27196812 TI - Ambivalence resolution in emotion-focused therapy: The successful case of Sarah. AB - : Ambivalence can be understood as a cyclical movement between two opposing positions of the self: one expressed in a novelty-an innovative moment (IM)-and another one conveyed by a return to the maladaptive pattern. If not properly addressed and resolved during therapy, ambivalence can prevent change and lead to psychotherapeutic failure. Two processes of ambivalence resolution have been suggested: (1) the dominance of the innovative position and consequent inhibition of the problematic position and (2) the negotiation between both positions. OBJECTIVES: To empirically study both processes of ambivalence resolution in a successful case of emotion-focused therapy. METHOD: Sessions were independently coded with three coding systems-the IMs, the return to the problem and the ambivalence resolution. RESULTS: Ambivalence tended to be resolved from the initial to the final sessions. Although resolutions through dominance tended to decrease and resolutions through negotiation seemingly increased along treatment, dominance was, nonetheless, the most prominent process of resolution along the whole treatment. CONCLUSIONS: Although it has been suggested that integrating opposing parts of the self is a necessary process for psychotherapeutic success, a less integrative process of ambivalence resolution may also be an important resource along the process. PMID- 27196815 TI - Evaluation of Cajanus cajan (pigeon pea) for phytoremediation of landfill leachate containing chromium and lead. AB - Landfill leachates containing heavy metals are important contaminants and a matter of great concern due to the effect that they might have on ecosystems. We evaluated the use of Cajanus cajan to remove chromium and lead from landfill leachates. Eight-week-old plants were submitted to varied tests to select the experimental conditions. Water assays with a solution (pH 6) containing leachate (25% v/v) were selected; the metals were added as potassium dichromate and lead (II) nitrate salts. Soil matrices that contained leachate (30% v/v) up to field capacity were used. For both water and soil assays, the metal concentrations were 10 mg kg(-1). C. cajan proved able to remove 49% of chromium and 36% of lead, both from dilute leachate. The plants also removed 34.7% of chromium from irrigated soil, but were unable to decrease the lead content. Removal of nitrogen from landfill leachate was also tested, resulting in elimination of 85% of ammonia and 70% of combined nitrite/nitrate species. The results indicate that C. cajan might be an effective candidate for the rhizofiltration of leachates containing chromium and lead, and nitrogen in large concentrations. PMID- 27196813 TI - A bedside test for methaemoglobinemia improved antidote use in propanil poisoning. AB - BACKGROUND: In 2008, self-poisoning with the herbicide propanil had a case fatality of around 11% in Sri Lanka. A simple quantitative methaemoglobinemia bedside test was developed so that treatment could be titrated according to the methaemoglobin level. OBJECTIVE: To determine whether the new method influenced patient management and changed the case fatality of propanil self-poisoning. METHOD: The bedside test (using an inexpensive validated colour chart) was introduced in three hospitals (Anuradhapura, Polonnaruwa and Galle) in Sri Lanka from 2008. Junior ward staff were given a brief training on how to use the chart for quantitative estimation of methaemoglobin in patients with propanil poisoning and utilize the results in the context of the national treatment guidelines for propanil poisoning. It was taught that the bedside test should be done repeatedly from admission until it showed consistently low values of methaemoglobin. Treatment with the antidote methylene blue was suggested for patients whose methaemoglobin was greater than 20%. Limited clinical data on poisoning have been prospectively collected from these hospitals from 2003. The case-fatality and management before and after the change were compared with data up to December 2014. RESULTS: The case-fatality decreased from (38/401) 9.5% to (8/262) 3.1% [difference: -6.4%, 95% CI: -10 to -3]. Methylene blue use increased from under 10% of patients before to 55% of patients after the intervention. More patients received repeat doses and infusions, and few received ascorbic acid and exchange transfusion. CONCLUSION: The simple bedside test for methaemoglobinemia was readily adopted into routine practice and led to large changes in management. A substantial reduction in mortality from propanil poisoning occurred after this intervention. PMID- 27196814 TI - Experience and challenges for biologic use in the treatment of moderate-to-severe psoriasis in Africa and the Middle East region. AB - The incidence of psoriasis in Africa and the Middle East (AfME) is high as in other regions and represents a significant problem for both dermatologists and patients. Psoriasis co-morbidities such as obesity, cardiovascular disease and psoriatic arthritis (PsA) are also particularly common in these regions and may be under-recognized and under-treated. Despite this, regional guidelines to aid physicians on the appropriate use of biologic agents in their clinical practice are limited. A group of expert dermatologists from across the AfME region were surveyed to help establish best practice across the region, alongside supporting data from the literature. Although biologics have significantly improved patient outcomes since their introduction, the results of this survey identified several unmet needs, including the lack of consensus regarding their use in clinical practice. Discrepancy also exists among AfME physicians concerning the clinical relevance of immunogenicity to biologics, despite increasing data across inflammatory diseases. Significant treatment and management of challenges for psoriasis patients remain, and a move towards individualized, tailored care may help to address these issues. The development of specific local guidelines for the treatment of both psoriasis and PsA could also be a step towards understanding the distinct patient profiles in these regions. PMID- 27196816 TI - Emergence of white pine needle damage in the northeastern United States is associated with changes in pathogen pressure in response to climate change. AB - The defoliation of the eastern white pine (Pinus strobus) across the northeastern United States is an escalating concern threatening the ecological health of northern forests and economic vitality of the region's lumber industry. First documented in the spring of 2010 affecting 24 328 hectares in the state of Maine, white pine needle damage (WPND) has continued to spread and is now well established in all New England states. While causal agents of WPND are known, current research is lacking in both sampling distribution and the specific environmental factor(s) that affect the development and spread of this disease complex. This study aims to construct a more detailed distribution map of the four primary causal agents within the region, as well as utilize long-term WPND monitoring plots and data collected from land-based weather stations to develop a climatic model to predict the severity of defoliation events in the proceeding year. Sampling results showed a greater distribution of WPND than previously reported. WPND was generally found in forest stands that compromised >50% eastern white pine by basal area. No single species, nor a specific combination of species had a dominating presence in particular states or regions, thus supporting the disease complex theory that WPND is neither caused by an individual species nor by a specific combination of species. In addition, regional weather data confirmed the trend of increasing temperature and precipitation observed in this region with the previous year's May, June, and July rainfall being the best predictor of defoliation events in the following year. Climatic models were developed to aid land managers in predicting disease severity and accordingly adjust their management decisions. Our results clearly demonstrate the role changing climate patterns have on the health of eastern white pine in the northeastern United States. PMID- 27196817 TI - Immediate-type hypersensitivity to polyethylene glycols: a review. AB - Polyethylene glycols (PEGs) or macrogols are polyether compounds widely used in medical and household products. Although generally considered biologically inert, cases of mild to life-threatening immediate-type PEG hypersensitivity are reported with increasing frequency. Nevertheless, awareness of PEG's allergenic potential remains low, due to a general lack of suspicion towards excipients and insufficient product labelling. Information on immediate-type reactions to PEG is limited to anecdotal reports, and the potential for PEG sensitization and cross sensitization to PEGylated drugs and structurally related derivatives is likely underestimated. Most healthcare professionals have no knowledge of PEG and thus do not suspect PEG's as culprit agents in hypersensitivity reactions. In consequence, patients are at risk of misdiagnosis and commonly present with a history of repeated, severe reactions to a range of unrelated products in hospital and at home. Increased awareness of PEG prevalence, PEG hypersensitivity, and improved access to PEG allergy testing, should facilitate earlier diagnosis and reduce the risk of inadvertent re-exposure. This first comprehensive review provides practical information for allergists and other healthcare professionals by describing the clinical picture of 37 reported cases of PEG hypersensitivity since 1977, summarizing instances where PEG hypersensitivity should be considered and proposing an algorithm for diagnostic management. PMID- 27196818 TI - Impact of magnetic resonance imaging on ventricular tachyarrhythmia sensing: Results of the Evera MRI Study. AB - BACKGROUND: Studies have shown that magnetic resonance imaging (MRI) conditional pacemakers experience no significant effect from MRI on device function, sensing, or pacing. More recently, similar safety outcomes were demonstrated with MRI conditional defibrillators (implantable cardioverter-defibrillator [ICD]), but the impact on ventricular arrhythmias has not been assessed. OBJECTIVE: The purpose of this study was to assess the effect of MRI on ICD sensing and treatment of ventricular tachyarrhythmias. METHODS: The Evera MRI Study was a worldwide trial of 156 patients implanted with an ICD designed to be MRI conditional. Device-detected spontaneous and induced ventricular tachycardia/ventricular fibrillation (VT/VF) episodes occurring before and after whole body MRI were evaluated by a blinded episode review committee. Detection delay was computed as the sum of RR intervals of undersensed beats. A >=5-second delay in detection due to undersensing was prospectively defined as clinically significant. RESULTS: Post-MRI, there were 22 polymorphic VT/VF episodes in 21 patients, with 16 of these patients having 17 VT/VF episodes pre-MRI. Therapy was successful for all episodes, with no failures to treat or terminate arrhythmias. The mean detection delay due to undersensing pre- and post-MRI was 0.60 +/- 0.59 and 0.33 +/- 0.63 seconds, respectively (P = .17). The maximum detection delay was 2.19 seconds pre-MRI and 2.87 seconds post-MRI. Of the 17 pre-MRI episodes, 14 (82%) had some detection delay as compared with 11 of 22 (50%) post-MRI episodes (P = .03); no detection delay was clinically significant. CONCLUSION: Detection and treatment of VT/VF was excellent, with no detection delays or significant impact of MRI observed. PMID- 27196820 TI - Microfluidic SAXS Study of Lamellar and Multilamellar Vesicle Phases of Linear Sodium Alkylbenzenesulfonate Surfactant with Intrinsic Isomeric Distribution. AB - The structure and flow behavior of a concentrated aqueous solution (45 wt %) of the ubiquitous linear sodium alkylbenzenesulfonate (NaLAS) surfactant is investigated by microfluidic small-angle X-ray scattering (SAXS) at 70 degrees C. NaLAS is an intrinsically complex mixture of over 20 surfactant molecules, presenting coexisting micellar (L1) and lamellar (Lalpha) phases. Novel microfluidic devices were fabricated to ensure pressure and thermal resistance, ability to handle viscous fluids, and low SAXS background. Polarized light optical microscopy showed that the NaLAS solution exhibits wall slip in microchannels, with velocity profiles approaching plug flow. Microfluidic SAXS demonstrated the structural spatial heterogeneity of the system with a characteristic length scale of 50 nL. Using a statistical flow-SAXS analysis, we identified the micellar phase and multiple coexisting lamellar phases with a continuous distribution of d spacings between 37.5 and 39.5 A. Additionally, we showed that the orientation of NaLAS lamellar phases is strongly affected by a single microfluidic constriction. The bilayers align parallel to the velocity field upon entering a constriction and perpendicular to it upon exiting. On the other hand, multilamellar vesicle phases are not affected under the same flow conditions. Our results demonstrate that despite the compositional complexity inherent to NaLAS, microfluidic SAXS can rigorously elucidate its structure and flow response. PMID- 27196819 TI - Multiplex polymerase chain reaction-based prognostic models in diffuse large B cell lymphoma patients treated with R-CHOP. AB - We present a multiplex analysis for genes known to have prognostic value in an attempt to design a clinically useful classification model in patients with diffuse large B-cell lymphoma (DLBCL). Real-time polymerase chain reaction was used to measure transcript levels of 28 relevant genes in 194 de novo DLBCL patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). Including International Prognostic Index (IPI) as a variable in a penalized Cox regression, we investigated the association with disease progression for single genes or gene combinations in four models. The best model was validated in data from an online available R-CHOP treated cohort. With progression-free survival (PFS) as primary endpoint, the best performing IPI independent model incorporated the LMO2 and HLADQA1 as well as gene interactions for GCSAMxMIB1, GCSAMxCTGF and FOXP1xPDE4B. This model assigned 33% of patients (n = 60) to poor outcome with an estimated 3-year PFS of 40% vs. 87% for low risk (n = 61) and intermediate (n = 60) risk groups (P < 0.001). However, a simpler, IPI independent model incorporated LMO2 and BCL2 and assigned 33% of the patients with a 3-year PFS of 35% vs. 82% for low risk group (P < 0.001). We have documented the impact of a few single genes added to IPI for assignment in new drug trials. PMID- 27196825 TI - Rules for Cyberwar. PMID- 27196821 TI - Country-Specific vs. Common Birthweight-for-Gestational Age References to Identify Small for Gestational Age Infants Born at 24-28 weeks: An International Study. AB - BACKGROUND: Controversy exists as to whether birthweight-for-gestational age references used to classify infants as small for gestational age (SGA) should be country specific or based on an international (common) standard. We examined whether different birthweight-for-gestational age references affected the association of SGA with adverse outcomes among very preterm neonates. METHODS: Singleton infants (n = 23 788) of 24(0) -28(6) weeks' gestational age in nine high-resource countries were classified as SGA (<10th centile) using common and country-specific references based on birthweight and estimated fetal weight (EFW). For each reference, the adjusted relative risk (aRR) for the association of SGA with composite outcome of mortality or major morbidity was estimated. RESULTS: The percentage of infants classified as SGA differed slightly for common compared with country specific for birthweight references [9.9% (95% CI 9.5, 10.2) vs. 11.1% (95% CI 10.7, 11.5)] and for EFW references [28.6% (95% CI 28.0, 29.2) vs. 24.6% (95% CI 24.1, 25.2)]. The association of SGA with the composite outcome was similar when using common or country-specific references for the total sample for birthweight [aRRs 1.47 (95% CI 1.43, 1.51) and 1.48 (95% CI 1.44, 1.53) respectively] and for EFW references [aRRs 1.35 (95% CI 1.31, 1.38) and 1.39 (95% CI 1.35, 1.43) respectively]. CONCLUSION: Small for gestational age is associated with higher mortality and morbidity in infants born <29 weeks' gestational age. Although common and country-specific birthweight/EFW references identified slightly different proportions of SGA infants, the risk of the composite outcome was comparable. PMID- 27196826 TI - The Collider That Could Save Physics. PMID- 27196822 TI - Coping and resiliency enhancement program (CARE): a pilot study for interpreters in cancer care. AB - OBJECTIVE: There is a growing demand for interpreters in the cancer setting. Interpreters, the link to quality care for limited English proficiency patients, face many psychosocial stressors in their work. This project assessed interpreters' experiences of stress and piloted a resiliency program to help interpreters cope with stressors. METHODS: From 2013 to 2014, we pilot tested a targeted resiliency program with interpreters from three Boston-based hospitals. In Phase 1, we conducted five focus groups (n = 31) to identify interpreters' psychosocial needs. In Phase 2, we developed and tested a 4-h group program with 29 interpreters (response rate = 90%; 69% female, 54% Hispanic, 85% born outside of the U.S.). RESULTS: Phase 1. Stressors were patient-based (seeing young patients decline), interactions with medical team (unsure of role), and systems based (appointment unpredictability). Phase 2. At baseline interpreters reported low abilities to cope with stress (measured by the Measure of Current Status (MOCS-A)). At 4-week follow-up we found improvements in job satisfaction (p = .02; Cohen's d = .41) and declines in sick days (p = .08; Cohen's d = .38). Stress reactivity (MOCS-A) improved; specifically participants reported feeling more assertive about their needs (p = .10; Cohen's d = .30) and more able to relax at will (p = .10; Cohen's d = .35)-important mechanisms to lower distress. CONCLUSIONS: We piloted a resiliency program for medical interpreters in cancer care. We found that interpreters experience distress and have low coping skills. This program resulted in improved work factors and stress reactivity. Future research should include further implementation and testing in a larger, randomized trial.Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27196827 TI - When DNA Implicates the Innocent. PMID- 27196828 TI - Ugly Critters Get No Love. PMID- 27196829 TI - A Northwest Passage for the Internet. PMID- 27196830 TI - Fast Faults. PMID- 27196831 TI - Lab Tech Opening: 249 Miles above Earth. PMID- 27196832 TI - Toddlers' Tool Kits. PMID- 27196834 TI - Eggshell Education. PMID- 27196835 TI - A Mental Unblock. PMID- 27196836 TI - Eyeglasses, No Prescription Necessary. PMID- 27196837 TI - A Plan to Prevent Gun Suicides. PMID- 27196838 TI - Hail, Robo-Taxi. PMID- 27196840 TI - Stellar Fireworks. PMID- 27196839 TI - Ascent of the Mammals. PMID- 27196843 TI - The Truth about "Self-Driving" Cars. PMID- 27196842 TI - Machines Who Learn. PMID- 27196844 TI - Should We Fear Supersmart Robots? PMID- 27196845 TI - Preventing Tomorrow's Climate Wars. PMID- 27196846 TI - Einstein of the Sea. PMID- 27196847 TI - The Fog of Agent Orange. PMID- 27196849 TI - Death Wish. PMID- 27196851 TI - 50, 100 &150 Years Ago. PMID- 27196852 TI - Can You Read This from a Distance? PMID- 27196854 TI - Rehabilitating a missed opportunity: Integration of rehabilitation psychology into the care of critically ill patients, survivors, and caregivers. AB - OBJECTIVE: Rehabilitation psychologists are specifically trained to work with individuals across the spectrum of health care settings and they have only recently begun to wade into the often deep and challenging waters of the critical care environment and intensive care unit (ICU) setting. METHOD: In the commentary that follows, we will provide a brief historical perspective on the involvement of rehabilitation psychologists in medical settings and we will describe and interact with the various topics raised in this current special section, all of them pertaining to the intersection of psychology and critical illness. RESULTS: These topics concern the potential role of psychologists in the ICU, the identification and treatment of conditions such as Post-Intensive Care Syndrome, the clinical nuances of cognitive impairment and psychological dysfunction after critical illness, and the legacy of critical illness on families. CONCLUSION: In light of the relevance of these and related topics, we argue in the commentary that the time for psychologists to become involved in the critical care arena is "now" and we discuss practical opportunities for such involvement. (PsycINFO Database Record PMID- 27196853 TI - Psychometric properties of the Cognitive and Linguistic Scale: A follow-up study. AB - OBJECTIVE: In a pediatric rehabilitation setting, monitoring recovery of cognitive skills is challenging due to diversity in age and brain injury severity. The Cognitive and Linguistic Scale (CALS) is a measure with promising psychometric properties that was designed for inpatient pediatric rehabilitation care. This study re-examines the reliability and validity of the CALS in a larger, independent sample. METHOD: Two hundred fifty-eight children (2-21 years) who were consecutively admitted to an inpatient brain injury facility between 2008 and 2014 for a first inpatient rehabilitation admission following a traumatic or acquired brain injury were included. Both CALS and Functional Independence Measure for Children (WeeFIM) were examined at admission and discharge. CALS scores by age groups (preschool-aged, school-aged, adolescents, or young adults), gender, and etiology (acquired vs. traumatic brain injury) and in two subgroups. RESULTS: The internal consistency of the CALS was high. Total CALS score and individual item scores improved significantly between admission and discharge for children of all age groups, both genders, both traumatic and acquired etiologies, and in subgroups with limited responsiveness and no change on the WeeFIM cognitive domain. No age group had a floor or ceiling effect. Correlations with the WeeFIM were high. Factor analysis revealed 2 factors (basic responding and higher-level cognitive skills). CONCLUSIONS: The CALS has strong psychometric properties across a wide range of ages, brain injury etiologies, and cognitive severity. The CALS can be used to track cognitive and linguistic recovery in children, adolescents, and young adults with brain injury during inpatient rehabilitation. (PsycINFO Database Record PMID- 27196855 TI - Is the intensive care unit traumatic? What we know and don't know about the intensive care unit and posttraumatic stress responses. AB - The intensive care unit (ICU) has been portrayed as psychologically stressful, with a growing body of research substantiating elevated rates of depression, posttraumatic stress disorder (PTSD), and other psychological disruptions in populations of critical care survivors. To explain these psychopathology elevations, some have proposed a direct effect of ICU admission upon the later development of psychopathology, whereas others highlight the complex interaction between the trauma of a life-threatening illness or injury and the stressful life saving interventions often administered in the ICU. However, the conclusion that the ICU is an independent causal factor in trauma-related psychological outcomes may be premature. Current ICU research suffers from important methodological problems including lack of true prospective data, failure to employ appropriate comparison groups, sampling bias, measurement issues, and problems with statistical methodology. In addition, the ICU literature has yet to investigate important risk and resilience factors that have been empirically validated in the broader stress-response literature. The authors propose the application of these important constructs to the unique setting of the ICU. This review focuses on multiple aspects of the important but complex research question of whether the ICU confers risk for psychological distress above and beyond the traumatic impact of the serious health events that necessitate ICU treatment. (PsycINFO Database Record PMID- 27196856 TI - Posttraumatic stress disorder (PTSD) after critical illness: A conceptual review of distinct clinical issues and their implications. AB - PURPOSE/OBJECTIVE: Posttraumatic stress disorder (PTSD) that develops after critical care may be marked by a unique constellation of symptoms that differ, for example, from the symptoms that develop in response to more traditional traumas such as combat or assault. RESEARCH METHOD/DESIGN: We describe ways in which symptoms of PTSD after critical illness can be clinically engaged, drawing from literature pointing to "best treatment" practices in other settings. And, we discuss the relevance of intensive care unit (ICU) related PTSD to rehabilitation psychologists and explain why rehabilitation psychologists are well suited to identify and treat ICU-related PTSD. RESULTS: In this conceptual review, drawing from both empirical findings and theoretical models, we surmise that traumatized survivors of critical illness demonstrate 2 central clinical features-avoidance and reexperiencing. CONCLUSIONS/IMPLICATIONS: The potentially unique clinical profile of ICU-related PTSD likely requires unique assessment and treatment practices. These services may be best provided by providers with expertise in providing coordinated care, such as rehabilitation psychologists. Next steps should include empirical study to determine whether practices that are empirically supported in other settings may be translated to the ICU and post-ICU hospitalization for critical illness survivors. (PsycINFO Database Record PMID- 27196857 TI - Posttraumatic stress symptoms in intensive care patients: An exploration of associated factors. AB - PURPOSE/OBJECTIVE: To explore demographic, clinical, and psychological factors in intensive care unit (ICU), including self-reported sleep quality and experiences that were associated with posttraumatic stress (PTS) symptoms 6 months after discharge from hospital. RESEARCH METHOD/DESIGN: A prospective survey was conducted (N = 222). On the day of transfer to the hospital ward, ICU patients reported pain and state-anxiety levels, as well as ICU and prehospital sleep quality. Two months after hospital discharge, they reported sleep quality at home and experiences in ICU. Six months after hospital discharge, sleep quality, PTS symptoms (measured with the Posttraumatic Stress Disorder Checklist-Specific; PCL S; VA National Center for PTSD, 2014) and psychological well-being (using Depression, Anxiety and Stress Scales-21; DASS-21; Ware, Kosinski, & Keller, 1994) were reported. Descriptive data analyses were performed and factors associated with PTS symptoms were explored with multiple linear regression. RESULTS: The sample was predominately male (65%), with a mean age 57 years. At baseline, pain intensity was low (M +/- SD; 2.25 +/- 1.14) and state-anxiety levels were moderate (2.50 +/- 2.90). At 6 months, 30% of the sample demonstrated depression, and 13.5% (mean PCL-S score: 26.54 +/- 10.52) reported symptoms reflective of PTS. The regression model explained 68.2% of the variance in the PCL-S score. Higher PTS scores were independently associated with frightening experiences in ICU, higher stress and depression scores, pain intensity at baseline, and sleep quality at 6 months. CONCLUSION/IMPLICATIONS: Continuing symptoms of PTS were evident in 14% of the cohort. Screening for prevention and treatment of delirium while a patient is in ICU is essential, and psychological screening and follow-up during recovery would therefore also be beneficial for many patients. (PsycINFO Database Record PMID- 27196859 TI - Caregiver strain and posttraumatic stress symptoms of informal caregivers of intensive care unit survivors. AB - BACKGROUND: Many intensive care unit survivors (ICU) are confronted with undesirable and long-lasting impairments in physical, cognitive, and mental health, but not only patients are at risk of developing this post-intensive care syndrome (PICS). Family members can experience symptoms of depression, anxiety, and posttraumatic stress disorder (PTSD). This cluster of complications is called PICS-family. OBJECTIVE: To describe the level of caregiver strain and posttraumatic stress-related symptoms in relatives of ICU survivors. METHODS: We conducted a cohort study in a general hospital between July 2010 and May 2014. Relatives of ICU survivors, mechanically ventilated for > 48 h in the ICU, were asked to complete a questionnaire 3 months after discharge from critical care. Symptoms of PTSD and caregiving concerns were assessed using the Trauma Screening Questionnaire and the Caregiver Strain Index (CSI). RESULTS: A total of 94 relatives visiting our post-ICU clinic completed the questionnaires. Twenty-one percent of the caregivers had a CSI score of 7 or more, indicating high levels of strain. Six percent had CSI scores indicating severe strain (CSI > 10). PTSD related symptoms were seen in 21% of the caregivers. The mean time spent on caregiving was 10 h (interquartile range 6-17 h) per week. CONCLUSION: This study shows that relatives of ICU survivors could experience strain 3 months after hospital discharge and are at risk of developing PTSD-related symptoms. This complements existing data that relatives are at risk of psychological symptoms. Knowledge can lead to improvements and means to prevent these symptoms. (PsycINFO Database Record PMID- 27196858 TI - Critical illness acquired brain injury: Neuroimaging and implications for rehabilitation. AB - OBJECTIVE: The increasing likelihood of surviving critical illness has resulted in a large and growing number of individuals transitioning from medical and surgical intensive care units (ICUs) to their homes. Many ICU survivors develop pervasive morbidities in physical, psychological, and cognitive functioning that adversely impact day-to-day functioning, ability to return to work, and quality of-life. These individuals have been extensively studied with neuropsychological test batteries, but relatively little research has been conducted using neuroimaging. This paper reviews neuroimaging findings in survivors of critical illness treated in medical or surgical ICUs. METHODS: We assessed the relationships between abnormalities on neuroimaging and cognitive outcomes and discussed the implications for rehabilitation. RESULTS: There are limited imaging studies in ICU survivors. These studies use a wide range of modalities including magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), fluid attenuated inversion recovery (FLAIR), and diffusion weighted imaging. Structural abnormalities in survivors of critical illness include cortical and subcortical lesions, white matter hyperintensities (WMHs), and generalized and focal atrophy. These abnormalities persist months to years after ICU discharge and are associated with cognitive impairments. (PsycINFO Database Record PMID- 27196860 TI - The intensive care unit experience: Psychological impact on family members of patients with and without traumatic brain injury. AB - PURPOSE/OBJECTIVE: The intensive care unit (ICU) has been identified as a possible contributor to emotional distress. This study seeks to identify whether families of traumatic brain injury (TBI) patients in the ICU experience psychological differences as compared with non-TBI patients' family members. METHOD: Eighty-two family members in a trauma/critical care ICU were assessed at baseline and again at 3 months. The Patient Health Questionnaire 8-Item measured depression, the Primary Care PTSD Screen measured symptoms of posttraumatic stress (PTS). RESULTS: Forty of these individuals were the family members of ICU patients who had sustained a TBI; 42 of the individuals were the family members of non-TBI patients in the ICU. At baseline, 39% (33% non-TBI, 45% TBI, p = .28) of the total sample screened positive for depressive symptoms and 24.3% (26% non TBI, 23% TBI, p = .69) screened positive for PTS symptoms. However, differences emerged between the groups at 3 months, with family members in the non-TBI group showing a significant decrease in both baseline depression and PTS symptoms. CONCLUSIONS/IMPLICATIONS: This study, to our knowledge, is the first of its kind to examine psychological differences in the ICU in those whose family members either have or do not have a TBI. Results suggest the TBI group endorsed more symptoms of depression and PTS symptoms at 3 months. Although it is unclear whether symptoms were directly related to the ICU experience or the injury itself, future research should explore the possible additive effect of postintensive care syndrome-family symptoms. (PsycINFO Database Record PMID- 27196861 TI - After critical care: Challenges in the transition to inpatient rehabilitation. AB - PURPOSE/OBJECTIVE: The aftermath of treatment for critical illness and/or critical injury in the intensive care unit (ICU) often includes persisting cognitive and emotional morbidities as well as severe physical deconditioning (a constellation termed post-intensive care syndrome, or PICS), but most patients do not receive psychological services before they enter the inpatient rehabilitation facility (IRF). Although a burgeoning literature guides the efforts of critical care providers to reduce risk factors for PICS - for example, reducing the use of sedatives and enacting early mobilization, there is need for a corresponding awareness among IRF psychologists and other providers that the post-ICU patient often arrives in a state of significantly reduced capacity, with persisting cognitive impairments and acute psychological distress. Many are at risk for long term complications of posttraumatic stress disorder, general anxiety and/or clinical depression, and assuredly all have experienced a profound life disruption. This paper offers a multilevel perspective on the adaptation of post ICU patients during inpatient rehabilitation, with discussion of the psychologist's role in education and intervention. RESEARCH METHOD/DESIGN: Clinical review paper. RESULTS: NA. CONCLUSIONS: To optimize response to rehabilitation, it is important to understand the behavior of post-ICU patients within a full biopsychosocial context including debility, cognitive and emotional impairment, disruption of role identities, and environmental factors. The psychologist can provide education about predictable barriers to participation for the post-ICU patient, and guide individual, family and team interventions to ameliorate those barriers. (PsycINFO Database Record PMID- 27196862 TI - A survey of psychology practice in critical-care settings. AB - PURPOSE/OBJECTIVE: The aims of this survey study were to (a) examine the frequency of health-service psychology involvement in intensive and critical-care settings; (b) characterize the distinguishing features of these providers; and (c) examine unique or distinguishing features of the hospital setting in which these providers are offering services. RESEARCH METHOD/DESIGN: chi2 analyses were conducted for group comparisons of health-service psychologists: (a) providing services in critical care versus those with no or limited critical care activity and (b) involved in both critical care and rehabilitation versus those only involved in critical care. RESULTS: A total of 175 surveys met inclusion criteria and were included in the analyses. Psychologists who worked in critical-care settings at least monthly were more likely to be at a Level-1, chi2(1, N = 157) = 9.654, p = .002, or pediatric, chi2(1, N = 158) = 7.081, p = .008, trauma center. Psychologists involved with critical care were more likely to provide services on general medical-surgical units, chi2(1, N = 167) = 45.679, p = .000. A higher proportion of rehabilitation-oriented providers provided intensive care, critical care, and neurointensive care services relative to nonrehabilitation providers. CONCLUSION/IMPLICATIONS: The findings indicate that health-service psychologists are involved in critical-care settings and in various roles. A more broad-based survey of hospitals across the United States would be required to identify how frequently health-service psychologists are consulted and what specific services are most effective, valued, or desired in critical-care settings. (PsycINFO Database Record PMID- 27196863 TI - The influence of psychological flexibility on life satisfaction and mood in muscle disorders. AB - PURPOSE/OBJECTIVE: Acceptance and commitment therapy (ACT), a newer type of behavior therapy that targets psychological flexibility, may have particular utility in the context of muscle disorders. However, there has been no formal investigation of psychological flexibility in this population. This longitudinal observational study investigated whether psychological flexibility is cross sectionally related to, and prospectively influential on, life satisfaction and mood in muscle disorders. METHODS: Data were collected via online questionnaire batteries, completed at baseline and then repeated 4 months later. Cross sectional and prospective regression analyses examined relationships between validated measures of disability level, psychological flexibility (experiential avoidance, cognitive fusion, and valued living) and illness perceptions (a psychological variable with known influence in muscle disorders), and outcomes (life satisfaction, anxiety, and depression). RESULTS: A sample of 137 people with a range of muscle disorders participated. In cross-sectional analyses, psychological flexibility explained significant unique variance in addition to illness perceptions (DeltaR2 = 0.17-0.34, p < .001). In prospective analyses, psychological flexibility alone was predictive of change in life satisfaction (DeltaR2 = 0.04, p = .01) and anxiety (DeltaR2 = 0.03, p = .04) over 4 months. No independent variables were predictive of change in depression over 4 months, and disability level had no significant influence on outcomes. CONCLUSIONS: Psychological flexibility influences important outcomes in muscle disorders. Experimental studies are required to establish if increased psychological flexibility leads to improved outcomes. (PsycINFO Database Record PMID- 27196864 TI - Clinical utility and psychometric properties of the Functional Assessment of Multiple Sclerosis for individuals with multiple sclerosis. AB - This Rehabilitation Measures Database summary provides a review of the psychometric properties of the FAMS in individuals with MS. A full review of the FAMS as well as reviews of over 300 other instruments can be found at www.rehabmeasures.org. (PsycINFO Database Record PMID- 27196869 TI - Review of the Pharmacological Effects of Vitis vinifera (Grape) and its Bioactive Constituents: An Update. AB - Vitis vinifera fruit (grape) contains various phenolic compounds, flavonoids and stilbenes. In recent years, active constituents found in the fruits, seeds, stems, skin and pomaces of grapes have been identified and some have been studied. In this review, we summarize the active constituents of different parts of V. vinifera and their pharmacological effects including skin protection, antioxidant, antibacterial, anticancer, antiinflammatory and antidiabetic activities, as well as hepatoprotective, cardioprotective and neuroprotective effects in experimental studies published after our 2009 review. Clinical and toxicity studies have also been examined. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27196870 TI - Dynamic Changes in Heart Rate Variability and Nasal Airflow Resistance during Nasal Allergen Provocation Test. AB - Allergic rhinitis is a major chronic respiratory disease and an immunoneuronal disorder. We aimed at providing further knowledge on the function of the neural system in nasal allergic reaction. Here, a method to assess simultaneously the nasal airflow resistance and the underlying function of autonomic nervous system (ANS) is presented and used during the nasal provocation of allergic and nonallergic subjects. Continuous nasal airflow resistance and spectral heart rate variability parameters show in detail the timing and intensity differences in subjects' reactions. After the provocation, the nasal airflow resistance of allergic subjects showed a positive trend, whereas LF/HF (Low Frequency/High Frequency) ratio and LF power showed a negative trend. This could imply a gradual sympathetic withdrawal in allergic subjects after the allergen provocation. The groups differed significantly by these physiological descriptors. The proposed method opens entirely new opportunities to research accurately concomitant changes in nasal breathing function and ANS. PMID- 27196872 TI - Study of the efficiency of anticoagulant rodenticides to control Mus musculus domesticus introgressed with Mus spretus Vkorc1. AB - BACKGROUND: Antivitamin K anticoagulant (AVK) rodenticides are commonly used to control rodent pests worldwide. They specifically inhibit the VKORC1 enzyme essential for the recycling of vitamin K, and thus prevent blood clotting and cause death by haemorrhage. Numerous mutations or polymorphisms of the Vkorc1 gene were reported in rodents, and some led to resistance to rodenticides. In house mice (Mus musculus domesticus), adaptive introgression of the Vkorc1 gene from the Algerian mouse (Mus spretus) was reported. This adaptive introgression causes the substitution of four amino acids in M. musculus domesticus. RESULTS: The consequences of introgression were assessed by (i) the characterisation of the in vivo resistant phenotype of adaptive Vkorc1spr -introgressed mice, (ii) the characterisation of the ex vivo resistance phenotype of the liver VKOR activity and (iii) the comparison of these results with the properties of recombinant VKORC1spr protein expressed in yeast. The resistance factor (from 1 to 120) induced by the four introgressed polymorphisms obtained using these three approaches was dependent on the AVKs used but were highly correlated among the three approaches. CONCLUSION: The four introgressed polymorphisms were clearly the cause of the strong resistant phenotype observed in the field. In the context of strong selection pressure due to the extensive use of AVKs, this resistant phenotype may explain the widespread distribution of this genotype from Spain to Germany. (c) 2016 Society of Chemical Industry. PMID- 27196876 TI - Burden of Visual Impairment and Chronic Diseases. AB - IMPORTANCE: Visual impairment (VI) is an emerging public health concern, especially considering the aging population. However, unlike other major chronic diseases, VI is often overlooked by investigators assessing the burden of diseases. OBJECTIVES: To provide a description of preference weights for VI and chronic diseases from a national survey and estimate the corresponding burden of these diseases. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study was conducted using a multistage, probability-cluster survey, which can produce nationally representative estimates. Data on 29 639 participants 19 years or older from the 2008-2012 Korean National Health and Nutrition Examination Survey were analyzed in terms of vision assessment, status of chronic diseases, and the European Quality of Life-Five Dimensions Questionnaire (EQ-5D). Visual impairment was defined as the presenting distance best-corrected visual acuity of worse than decimal 0.5. Data analysis was conducted from August 14, 2008, and September 7, 2015. MAIN OUTCOMES AND MEASURES: Preference weights (utilities) and prevalence based quality-adjusted life-year (QALY) losses. RESULTS: Of the 29 639 participants, 28 382 with VA or EQ-5D measurements were included in the analysis; they had a mean (SE) age of 45.05 (0.19) years and a mean EQ-5D index of 0.948 (0.001). The preference weight for VI was -0.0549 (95% CI, -0.0777 to -0.0321), which was the third highest value among the 12 diseases analyzed-preceded only by the preference weights for osteoarthritis or rheumatoid arthritis (-0.0688; 95% CI, -0.748 to -0.0628) and stroke (-0.0666; 95% CI, -0.0854 to -0.0479). The estimated annual QALY loss from VI was -74.93 years per 100 000 person-years; this loss is comparable to or higher than that associated with other major chronic conditions (eg, diabetes mellitus, dyslipidemia, stroke, myocardial infarction/ischemic heart disease, asthma, obesity, and anemia). Visual impairment accounted for 4.77% of the total estimated QALY loss in the Korean population aged 19 years or older. CONCLUSIONS AND RELEVANCE: The present study provides a description of preference weights for VI and various chronic diseases from a national survey. Furthermore, it reveals the distributions of public burden from these conditions, and compared them in this regard. Although details might vary across the populations having different cultural and socioeconomic backgrounds, the results underscore the importance of VI for quality of life and as a public health burden compared with other major chronic diseases. PMID- 27196877 TI - Efficient synthesis of triarylamine-based dyes for p-type dye-sensitized solar cells. AB - The class of triarylamine-based dyes has proven great potential as efficient light absorbers in inverse (p-type) dye sensitized solar cells (DSSCs). However, detailed investigation and further improvement of p-type DSSCs is strongly hindered by the fact that available synthesis routes of triarylamine-based dyes are inefficient and particularly demanding with regard to time and costs. Here, we report on an efficient synthesis strategy for triarylamine-based dyes for p type DSSCs. A protocol for the synthesis of the dye-precursor (4-(bis(4 bromophenyl)amino)benzoic acid) is presented along with its X-ray crystal structure. The dye precursor is obtained from the commercially available 4(diphenylamino)benzaldehyde in a yield of 87% and serves as a starting point for the synthesis of various triarylamine-based dyes. Starting from the precursor we further describe a synthesis protocol for the dye 4-{bis[4'-(2,2-dicyanovinyl) [1,1'-biphenyl]-4-yl]amino}benzoic acid (also known as dye P4) in a yield of 74%. All synthesis steps are characterized by high yields and high purities without the need for laborious purification steps and thus fulfill essential requirements for scale-up. PMID- 27196878 TI - Finding and Producing Probiotic Glycosylases for the Biocatalysis of Ginsenosides: A Mini Review. AB - Various microorganisms have been widely applied in nutraceutical industries for the processing of phytochemical conversion. Specifically, in the Asian food industry and academia, notable attention is paid to the biocatalytic process of ginsenosides (ginseng saponins) using probiotic bacteria that produce high levels of glycosyl-hydrolases. Multiple groups have conducted experiments in order to determine the best conditions to produce more active and stable enzymes, which can be applicable to produce diverse types of ginsenosides for commercial applications. In this sense, there are various reviews that cover the biofunctional effects of multiple types of ginsenosides and the pathways of ginsenoside deglycosylation. However, little work has been published on the production methods of probiotic enzymes, which is a critical component of ginsenoside processing. This review aims to investigate current preparation methods, results on the discovery of new glycosylases, the application potential of probiotic enzymes and their use for biocatalysis of ginsenosides in the nutraceutical industry. PMID- 27196879 TI - Regioselective Palmitoylation of 9-(2,3-Dihydroxy- propyl)adenine Catalyzed by a Glycopolymer-enzyme Conjugate. AB - The enzymatic regioselective monopalmitoylation of racemic 9-(2,3 dihydroxypropyl)- adenine (DHPA), an approved antiviral agent, has been performed by an immobilized form of Candida antarctica B lipase (CAL-B) using a 4:1 DMF/hexane mixture as the reaction medium. To improve the chemical yield of the desired monopalmitoylation reaction, solid-phase chemical modifications of the lipase were evaluated. The reaction yield was successfully increased obtaining 100% product after a second treatment of the product solution with fresh immobilised chemically glycosylated-CAL-B. PMID- 27196880 TI - Naturally Inspired Molecules as Multifunctional Agents for Alzheimer's Disease Treatment. AB - Alzheimer's disease (AD) has been defined as a multi-factorial disorder resulting from a complex array of networked cellular and molecular mechanisms. In particular, elevated levels of Abeta protein and its aggregation products in the presence of metal ions proved to be highly neurotoxic and therapeutic strategies aimed at preventing Abeta generation and oxidative stress may represent an effective approach for AD treatment. A recent paradigm for the treatment of complex diseases such as AD suggests the employment of multifunctional compounds, single chemical entities capable of simultaneously modulating different targets involved in the pathology. In this paper, the "pharmacophores combination" strategy was applied, connecting the main scaffold of the BACE-1 ligand 1 to that of the chalcone 2, as metal chelating pharmacophore, to obtain a small library of compounds. Conjugate 5 emerged as the most interesting derivative, proving to inhibit BACE-1 with low-micromolar potency, and showing neuroprotective effects. In particular, 5 proved to be able to protect from metal-associated oxidative stress by hampering intracellular Cu(2+)-induced ROS formation without any direct neurotoxic effect. PMID- 27196881 TI - In Vitro Antioxidant, Anti-Diabetes, Anti-Dementia, and Inflammation Inhibitory Effect of Trametes pubescens Fruiting Body Extracts. AB - Trametes pubescens, white rot fungus, has been used for folk medicine in Asian countries to treat ailments such as cancer and gastrointestinal diseases. This study was initiated to evaluate the in vitro antioxidant, anti-diabetes, anti dementia, and anti-inflammatory activities of T. pubescens fruiting bodies. The 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical scavenging activities of T. pubescens methanol (ME) and hot water (HWE) extracts (2.0 mg/mL) were comparable to butylated hydroxytoluene (BHT), the positive control. However, the chelating effects of ME and HWE were significantly higher than that of BHT. The HWE (6 mg/mL) also showed comparable reducing power to BHT. Eleven phenol compounds were detected by high performance liquid chromatography (HPLC) analysis. The alpha amylase and alpha-glucosidase inhibitory activities of the ME and HWE of the mushroom were lower than Acarbose, the standard reference; however, the inhibitory effects of the mushroom extracts at 2.0 mg/mL were moderate. The acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory effects of ME and HWE were moderate and comparable with galanthamine, the standard drug to treat early stages of Alzheimer's disease (AD). The ME had a neuroprotective effect against glutamate-induced PC-12 cell cytotoxicity at the concentration range of 2-40 MUg/mL. The mushroom extracts also showed inflammation inhibitory activities such as production of nitric oxide (NO) and expression of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-induced murine macrophage-like cell lines (RAW 264.7) and significantly suppressed the carrageenan-induced rat paw-edema. Therefore, fruiting body extracts of T. pubescens demonstrated antioxidant related anti-diabetes, anti-dementia and anti inflammatory activities. PMID- 27196882 TI - Reversible Immobilization of Lipases on Heterofunctional Octyl-Amino Agarose Beads Prevents Enzyme Desorption. AB - Two different heterofunctional octyl-amino supports have been prepared using ethylenediamine and hexylendiamine (OCEDA and OCHDA) and utilized to immobilize five lipases (lipases A (CALA) and B (CALB) from Candida antarctica, lipases from Thermomyces lanuginosus (TLL), from Rhizomucor miehei (RML) and from Candida rugosa (CRL) and the phospholipase Lecitase Ultra (LU). Using pH 5 and 50 mM sodium acetate, the immobilizations proceeded via interfacial activation on the octyl layer, after some ionic bridges were established. These supports did not release enzyme when incubated at Triton X-100 concentrations that released all enzyme molecules from the octyl support. The octyl support produced significant enzyme hyperactivation, except for CALB. However, the activities of the immobilized enzymes were usually slightly higher using the new supports than the octyl ones. Thermal and solvent stabilities of LU and TLL were significantly improved compared to the OC counterparts, while in the other enzymes the stability decreased in most cases (depending on the pH value). As a general rule, OCEDA had lower negative effects on the stability of the immobilized enzymes than OCHDA and while in solvent inactivation the enzyme molecules remained attached to the support using the new supports and were released using monofunctional octyl supports, in thermal inactivations this only occurred in certain cases. PMID- 27196883 TI - A New Canthinone-Type Alkaloid Isolated from Ailanthus altissima Swingle. AB - The present investigation of the chemical constituents of the stem barks of Ailanthus altissima has resulted in the isolation of six canthinone-type alkaloids, including a new compound, (R)-5-(1-hydroxyethyl)-canthine-6-one (1), and five known compounds (2-6). Moreover, four phenyl propanoids (7-10), two lignans (11 and 12), two triterpenoids (13 and 14) and a fatty acid (15) having previously known chemical structures were isolated during the same course of this study. The structure of the new compound was elucidated by physical (m.p., [alpha]D) and spectroscopic data (1H-NMR, (13)C-NMR, 2D NMR, and HR-DART-MS) interpretation and its absolute configuration was determined by electronic circular dichroism (ECD) data and quantum chemical calculations. The inflammatory activities of the isolates were screened on lipopolysaccharide (LPS)-induced nitric oxide (NO), a proinflammatory mediator, in RAW 264.7 cells. Among these isolated compounds, six compounds exhibited significant inhibition of NO production, with IC50 values in the range of 5.92 +/- 0.9 to 15.09 +/- 1.8 MUM. PMID- 27196884 TI - MASM, a Matrine Derivative, Offers Radioprotection by Modulating Lethal Total Body Irradiation-Induced Multiple Signaling Pathways in Wistar Rats. AB - Matrine is an alkaloid extracted from Sophora flavescens Ait and has many biological activities, such as anti-inflammatory, antitumor, anti-fibrosis, and immunosuppressive properties. In our previous studies, the matrine derivative MASM was synthesized and exhibited potent inhibitory activity against liver fibrosis. In this study, we mainly investigated its protection against lethal total-body irradiation (TBI) in rats. Administration of MASM reduced the radiation sickness characteristics and increased the 30-day survival of rats before or after lethal TBI. Ultrastructural observation illustrated that pretreatment of rats with MASM significantly attenuated the TBI-induced morphological changes in the different organs of irradiated rats. Gene expression profiles revealed that pretreatment with MASM had a dramatic effect on gene expression changes caused by TBI. Pretreatment with MASM prevented differential expression of 53% (765 genes) of 1445 differentially expressed genes induced by TBI. Pathway enrichment analysis indicated that these genes were mainly involved in a total of 21 pathways, such as metabolic pathways, pathways in cancer, and mitogen-activated protein kinase (MAPK) pathways. Our data indicated that pretreatment of rats with MASM modulated these pathways induced by TBI, suggesting that the pretreatment with MASM might provide the protective effects on lethal TBI mainly or partially through the modulation of these pathways, such as multiple MAPK pathways. Therefore, MASM has the potential to be used as an effective therapeutic or radioprotective agent to minimize irradiation damages and in combination with radiotherapy to improve the efficacy of cancer therapy. PMID- 27196885 TI - A Convenient Synthesis of 3,7'-Bisindole Derivatives. AB - An efficient and convenient method to synthesize highly functionalized 3,7' bisindole derivatives has been developed via a Michael addition and cyclic condensation reaction of heterocyclic ketene aminals (HKAs) with 2-(1H-indol-3 yl)cyclohexa-2,5-diene-1,4-dione derivatives in ethanol-based solvents at room temperature. This strategy provides an efficient, environmentally friendly approach for easy access to various novel 3,7'-bisindole derivatives in moderate to good yields. PMID- 27196886 TI - Ethyl Acetate Abatement on Copper Catalysts Supported on Ceria Doped with Rare Earth Oxides. AB - Different lanthanide (Ln)-doped cerium oxides (Ce0.5Ln0.5O1.75, where Ln: Gd, La, Pr, Nd, Sm) were loaded with Cu (20 wt. %) and used as catalysts for the oxidation of ethyl acetate (EtOAc), a common volatile organic compound (VOC). For comparison, both Cu-free (Ce-Ln) and supported Cu (Cu/Ce-Ln) samples were characterized by N2 adsorption at -196 degrees C, scanning/transmission electron microscopy, energy-dispersive X-ray spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy and temperature programmed reduction in H2. The following activity sequence, in terms of EtOAc conversion, was found for bare supports: CeO2 ~ Ce0.5Pr0.5O1.75 > Ce0.5Sm0.5O1.75 > Ce0.5Gd0.5O1.75 > Ce0.5Nd0.5O1.75 > Ce0.5La0.5O1.75. Cu addition improved the catalytic performance, without affecting the activity order. The best catalytic performance was obtained for Cu/CeO2 and Cu/Ce0.5Pr0.5O1.75 samples, both achieving complete EtOAc conversion below ca. 290 degrees C. A strong correlation was revealed between the catalytic performance and the redox properties of the samples, in terms of reducibility and lattice oxygen availability. Nuo particular correlation between the VOC oxidation performance and textural characteristics was found. The obtained results can be explained in terms of a Mars-van Krevelen type redox mechanism involving the participation of weakly bound (easily reduced) lattice oxygen and its consequent replenishment by gas phase oxygen. PMID- 27196887 TI - Taxanes in the Treatment of Advanced Gastric Cancer. AB - Although rapid advances in treatment options have improved the prognosis of advanced gastric cancer (AGC), it remains a major public health problem and the second leading cause of cancer-related deaths in the world. Taxanes (paclitaxel and docetaxel) are microtubule stabilizing agents that inhibit the process of cell division, and have shown antitumor activity in the treatment of AGC as a single or combination chemotherapy. Accordingly, this review focuses on the efficacy and tolerability of taxanes in the first- or second-line chemotherapy setting for AGC. PMID- 27196889 TI - De Novo Sequencing and Transcriptome Analysis of Pleurotus eryngii subsp. tuoliensis (Bailinggu) Mycelia in Response to Cold Stimulation. AB - Cold stimulation of Bailinggu's mycelia is the main factor that triggers primordia initiation for successful production of fruiting bodies under commercial cultivation. Yet, the molecular-level mechanisms involved in mycelia response to cold stimulation are still unclear. Here, we performed comparative transcriptomic analysis using RNA-Seq technology to better understand the gene expression regulation during different temporal stages of cold stimulation in Bailinggu. A total of 21,558 Bailinggu mycelia unigenes were de novo assembled and annotated from four libraries (control at 25 degrees C, plus cold stimulation treatments at -3 degrees C for a duration of 1-2 days, 5-6 days, and 9-10 days). GO and KEGG pathway analysis indicated that functional groups of differentially expressed unigenes associated with cell wall and membrane stabilization, calcium signaling and mitogen-activated protein kinases (MAPK) pathways, and soluble sugars and protein biosynthesis and metabolism pathways play a vital role in Bailinggu's response to cold stimulation. Six hundred and seven potential EST-based SSRs loci were identified in these unigenes, and 100 EST-SSR primers were randomly selected for validation. The overall polymorphism rate was 92% by using 10 wild strains of Bailinggu. Therefore, these results can serve as a valuable resource for a better understanding of the molecular mechanisms associated with Bailinggu's response to cold stimulation. PMID- 27196888 TI - Regioselective Benzoylation of Diols and Carbohydrates by Catalytic Amounts of Organobase. AB - A novel metal-free organobase-catalyzed regioselective benzoylation of diols and carbohydrates has been developed. Treatment of diol and carbohydrate substrates with 1.1 equiv. of 1-benzoylimidazole and 0.2 equiv. of 1,8 diazabicyclo[5.4.0]undec-7-ene (DBU) in MeCN under mild conditions resulted in highly regioselective benzoylation for the primary hydroxyl group. Importantly, compared to most commonly used protecting bulky groups for primary hydroxyl groups, the benzoyl protective group offers a new protection strategy. PMID- 27196890 TI - Key Developments in Ionic Liquid Crystals. AB - Ionic liquid crystals are materials that combine the classes of liquid crystals and ionic liquids. The first one is based on the multi-billion-dollar flat panel display industry, whilst the latter quickly developed in the past decades into a family of highly-tunable non-volatile solvents. The combination yields materials with a unique set of properties, but also with many challenges ahead. In this review, we provide an overview of the key concepts in ionic liquid crystals, particularly from a molecular perspective. What are the important molecular parameters that determine the phase behavior? How should they be introduced into the molecules? Finally, which other tools does one have to realize specific properties in the material? PMID- 27196892 TI - Correction: Chan, Y.-Y., et al. The Constituents of Michelia compressa var. formosana and Their Bioactivities. Int. J. Mol. Sci. 2014, 15, 10926-10935. AB - The authors wish to make two changes to their published paper [1]. [...]. PMID- 27196891 TI - Mechanisms of Cell Killing Response from Low Linear Energy Transfer (LET) Radiation Originating from (177)Lu Radioimmunotherapy Targeting Disseminated Intraperitoneal Tumor Xenografts. AB - Radiolabeled antibodies (mAbs) provide efficient tools for cancer therapy. The combination of low energy beta(-)-emissions (500 keVmax; 130 keVave) along with a gamma-emission for imaging makes (177)Lu (T1/2 = 6.7 day) a suitable radionuclide for radioimmunotherapy (RIT) of tumor burdens possibly too large to treat with alpha-particle radiation. RIT with (177)Lu-trastuzumab has proven to be effective for treatment of disseminated HER2 positive peritoneal disease in a pre-clinical model. To elucidate mechanisms originating from this RIT therapy at the molecular level, tumor bearing mice (LS-174T intraperitoneal xenografts) were treated with (177)Lu-trastuzumab comparatively to animals treated with a non-specific control, (177)Lu-HuIgG, and then to prior published results obtained using (212)Pb trastuzumab, an alpha-particle RIT agent. (177)Lu-trastuzumab induced cell death via DNA double strand breaks (DSB), caspase-3 apoptosis, and interfered with DNA PK expression, which is associated with the repair of DNA non-homologous end joining damage. This contrasts to prior results, wherein (212)Pb-trastuzumab was found to down-regulate RAD51, which is involved with homologous recombination DNA damage repair. (177)Lu-trastuzumab therapy was associated with significant chromosomal disruption and up-regulation of genes in the apoptotic process. These results suggest an inhibition of the repair mechanism specific to the type of radiation damage being inflicted by either high or low linear energy transfer radiation. Understanding the mechanisms of action of beta(-)- and alpha-particle RIT comparatively through an in vivo tumor environment offers real information suitable to enhance combination therapy regimens involving alpha- and beta(-) particle RIT for the management of intraperitoneal disease. PMID- 27196893 TI - Recent Progress in Treating Protein-Ligand Interactions with Quantum-Mechanical Methods. AB - We review the first successes and failures of a "new wave" of quantum chemistry based approaches to the treatment of protein/ligand interactions. These approaches share the use of "enhanced", dispersion (D), and/or hydrogen-bond (H) corrected density functional theory (DFT) or semi-empirical quantum mechanical (SQM) methods, in combination with ensemble weighting techniques of some form to capture entropic effects. Benchmark and model system calculations in comparison to high-level theoretical as well as experimental references have shown that both DFT-D (dispersion-corrected density functional theory) and SQM-DH (dispersion and hydrogen bond-corrected semi-empirical quantum mechanical) perform much more accurately than older DFT and SQM approaches and also standard docking methods. In addition, DFT-D might soon become and SQM-DH already is fast enough to compute a large number of binding modes of comparably large protein/ligand complexes, thus allowing for a more accurate assessment of entropic effects. PMID- 27196896 TI - Postprandial C-Peptide to Glucose Ratio as a Marker of beta Cell Function: Implication for the Management of Type 2 Diabetes. AB - C-peptide is secreted from pancreatic beta cells at an equimolar ratio to insulin. Since, in contrast to insulin, C-peptide is not extracted by the liver and other organs, C-peptide reflects endogenous insulin secretion more accurately than insulin. C-peptide is therefore used as a marker of beta cell function. C peptide has been mainly used to assess the presence of an insulin-dependent state for the diagnosis of type 1 diabetes. However, recent studies have revealed that beta cell dysfunction is also a core deficit of type 2 diabetes, and residual beta cell function is a key factor in achieving optimal glycemic control in patients with type 2 diabetes. This review summarizes the role of C-peptide, especially the postprandial C-peptide to glucose ratio which likely better reflects maximum beta cell secretory capacity compared with the fasting ratio in assessing beta cell function, and discusses perspectives on its clinical utility for managing glycemic control in patients with type 2 diabetes. PMID- 27196894 TI - A Novel Prostate-Specific Membrane-Antigen (PSMA) Targeted Micelle-Encapsulating Wogonin Inhibits Prostate Cancer Cell Proliferation via Inducing Intrinsic Apoptotic Pathway. AB - Prostate cancer (PCa) is a malignant tumor for which there are no effective treatment strategies. In this study, we developed a targeted strategy for prostate-specific membrane-antigen (PSMA)-positive PCa in vitro based on 2-(3 ((S)-5-amino-1-carboxypentyl)ureido) pentanedioic acid (ACUPA) modified polyethylene glycol (PEG)-Cholesterol micelles containing wogonin (WOG), which was named ACUPA-M-WOG. ACUPA-M-WOG was conventionally prepared using a self assembling method, which produced stable particle size and zeta potential. Moreover, ACUPA-M-WOG showed good drug encapsulating capacity and drug release profiles. Fluorescence activated cell sorting (FACS) results suggested that ACUPA modified PEG-Cholesterol micelles could effectively enhance the drug uptake on PSMA(+) PCa cells, and the cytotoxicity of ACUPA-M-WOG was stronger than other controls according to in vitro cellular proliferation and apoptosis assays, separately through methyl thiazolyl tetrazolium (MTT) and Annexin V/Propidium Iodide (PI) staining. Finally, the molecular mechanisms of ACUPA-M-WOG's effects on human PSMA(+) PCa were investigated, and were mainly the intrinsic or extrinsic apoptosis signaling pathways. The Western blot results suggested that ACUPA-M-WOG could enhance the WOG-induced apoptosis, which was mainly via the intrinsic signaling pathway rather than the extrinsic signaling pathway. In conclusion, ACUPA-M-WOG was successfully developed for WOG-selective delivery to PSMA(+) PCa cells and had stronger inhibition than free drugs, which might make it an effective strategy for PSMA(+) PCa. PMID- 27196895 TI - Passive Immune-Protection of Litopenaeus vannamei against Vibrio harveyi and Vibrio parahaemolyticus Infections with Anti-Vibrio Egg Yolk (IgY)-Encapsulated Feed. AB - Vibrio spp. are major causes of mortality in white shrimp (Litopenaeus vannamei) which is lacking adaptive immunity. Passive immunization with a specific egg yolk antibody (IgY) is a potential method for the protection of shrimp against vibriosis. In this study, immune effects of the specific egg yolk powders (IgY) against both V. harveyi and V. parahaemolyticus on white shrimp were evaluated. The egg yolk powders against V. harveyi and V. parahaemolyticus for passive immunization of white shrimp were prepared, while a tube agglutination assay and an indirect enzyme-linked immunosorbent assay (ELISA) were used for detection of IgY titer. Anti-Vibrio egg yolk was encapsulated by beta-cyclodextrin, which could keep the activity of the antibody in the gastrointestinal tract of shrimp. The results showed that the anti-Vibrio egg powders had an inhibiting effect on V. harveyi and V. parahaemolyticus in vitro. Lower mortality of infected zoeae, mysis, and postlarva was observed in groups fed with anti-Vibrio egg powders, compared with those fed with normal egg powders. The bacterial load in postlarva fed with specific egg powders in seeding ponds was significantly lower than those fed with normal egg powders in seeding ponds. These results show that passive immunization by oral administration with specific egg yolk powders (IgY) may provide a valuable protection of vibrio infections in white shrimp. PMID- 27196898 TI - Clinical and Molecular Characterization of Patients with Mucopolysaccharidosis Type I in an Algerian Series. AB - Mucopolysaccharidoses (MPS's) represent a subgroup of lysosomal storage diseases related to a deficiency of enzymes that catalyze glycosaminoglycans degradation. Mucopolysaccharidosis type I (MPS I) is a rare autosomal recessive disorder caused by a deficiency of alpha-l-iduronidase encoded by the IDUA gene. Partially degraded heparan sulfate and dermatan sulfate accumulate progressively and lead to multiorgan dysfunction and damage. The aim of this study is to describe the clinical, biochemical, and molecular characteristics of 13 Algerian patients from 11 distinct families. MPS I diagnosis was confirmed by molecular study of the patients' IDUA gene. Clinical features at the diagnosis and during the follow-up are reported. Eighty-four percent of the studied patients presented with a mild clinical phenotype. Molecular study of the IDUA gene allowed the characterization of four pathological variations at the homozygous or compound heterozygote status: IDUA NM_00203.4:c.1598C>G-p.(Pro533Arg) in 21/26 alleles, IDUA NM_00203.4:c.532G>A-p.(Glu178Lys) in 2/26 alleles, IDUA NM_00203.4:c.501C>G p.(Tyr167*) in 2/26 alleles, and IDUA NM_00203. 4: c.1743C>G-p.(Tyr581*) in 1/26 alleles. This molecular study unveils the predominance of p.(Pro533Arg) variation in our MPS I patients. In this series, the occurrence of some clinical features linked to the Scheie syndrome is consistent with the literature, such as systematic valvulopathies, corneal opacity, and umbilical hernia; however, storage signs, facial dysmorphic features, and hepatomegaly were more frequent in our series. Screening measures for these debilitating diseases in highly consanguineous at-risk populations must be considered a priority health problem. PMID- 27196897 TI - Understanding the Functions of Long Non-Coding RNAs through Their Higher-Order Structures. AB - Although thousands of long non-coding RNAs (lncRNAs) have been discovered in eukaryotes, very few molecular mechanisms have been characterized due to an insufficient understanding of lncRNA structure. Therefore, investigations of lncRNA structure and subsequent elucidation of the regulatory mechanisms are urgently needed. However, since lncRNA are high molecular weight molecules, which makes their crystallization difficult, obtaining information about their structure is extremely challenging, and the structures of only several lncRNAs have been determined so far. Here, we review the structure-function relationships of the widely studied lncRNAs found in the animal and plant kingdoms, focusing on the principles and applications of both in vitro and in vivo technologies for the study of RNA structures, including dimethyl sulfate-sequencing (DMS-seq), selective 2'-hydroxyl acylation analyzed by primer extension-sequencing (SHAPE seq), parallel analysis of RNA structure (PARS), and fragmentation sequencing (FragSeq). The aim of this review is to provide a better understanding of lncRNA biological functions by studying them at the structural level. PMID- 27196899 TI - Long-Term Follow-up of HPV Infection Using Urine and Cervical Quantitative HPV DNA Testing. AB - The link between infection with high-risk human papillomavirus (hrHPV) and cervical cancer has been clearly demonstrated. Virological end-points showing the absence of persistent HPV infection are now accepted as a way of monitoring the impact of prophylactic vaccination programs and therapeutic vaccine trials. This study investigated the use of urine samples, which can be collected by self sampling at home, instead of cervical samples for follow-up of an HPV intervention trial. Eighteen initially HPV DNA-positive women participating in an HPV therapeutic vaccine trial were monitored during a three-year follow-up period. A total of 172 urine samples and 85 cervical samples were collected. We obtained a paired urine sample for each of the 85 cervical samples by recovering urine samples from six monthly gynaecological examinations. We performed a small pilot study in which the participating women used a urine collection device at home and returned their urine sample to the laboratory by mail. All samples were analyzed using quantitative real-time HPV DNA PCR. A good association (kappa value of 0.65) was found between the presence of HPV DNA in urine and a subsequent cervical sample. Comparisons of the number of HPV DNA copies in urine and paired cervical samples revealed a significant Spearman rho of 0.676. This correlation was superior in women with severe lesions. The HPV DNA results of the small pilot study based on self-collected urine samples at home are consistent with previous and subsequent urine and/or cervical results. We demonstrated that urine sampling may be a valid alternative to cervical samples for the follow-up of HPV intervention trials or programs. The potential clinical value of urine viral load monitoring should be further investigated. PMID- 27196900 TI - "Fifty Shades" of Black and Red or How Carboxyl Groups Fine Tune Eumelanin and Pheomelanin Properties. AB - Recent advances in the chemistry of melanins have begun to disclose a number of important structure-property-function relationships of crucial relevance to the biological role of human pigments, including skin (photo) protection and UV susceptibility. Even slight variations in the monomer composition of black eumelanins and red pheomelanins have been shown to determine significant differences in light absorption, antioxidant, paramagnetic and redox behavior, particle morphology, surface properties, metal chelation and resistance to photo oxidative wear-and-tear. These variations are primarily governed by the extent of decarboxylation at critical branching points of the eumelanin and pheomelanin pathways, namely the rearrangement of dopachrome to 5,6-dihydroxyindole (DHI) and 5,6-dihydroxyindole-2-carboxylic acid (DHICA), and the rearrangement of 5-S cysteinyldopa o-quinoneimine to 1,4-benzothiazine (BTZ) and its 3-carboxylic acid (BTZCA). In eumelanins, the DHICA-to-DHI ratio markedly affects the overall antioxidant and paramagnetic properties of the resulting pigments. In particular, a higher content in DHICA decreases visible light absorption and paramagnetic response relative to DHI-based melanins, but markedly enhances antioxidant properties. In pheomelanins, likewise, BTZCA-related units, prevalently formed in the presence of zinc ions, appear to confer pronounced visible and ultraviolet A (UVA) absorption features, accounting for light-dependent reactive oxygen species (ROS) production, whereas non-carboxylated benzothiazine intermediates seem to be more effective in inducing ROS production by redox cycling mechanisms in the dark. The possible biological and functional significance of carboxyl retention in the eumelanin and pheomelanin pathways is discussed. PMID- 27196902 TI - Anchoring of FRET Sensors-A Requirement for Spatiotemporal Resolution. AB - FRET biosensors have become a routine tool for investigating mechanisms and components of cell signaling. Strategies for improving them for particular applications are continuously sought. One important aspect to consider when designing FRET probes is the dynamic distribution and propagation of signals within living cells. We have addressed this issue by directly comparing an anchored (taFS) to a non-anchored (naFS) cleavable FRET sensor. We chose a microtubule-associated protein tau as an anchor, as microtubules are abundant throughout the cytosol of cells. We show that tau-anchored FRET sensors are concentrated at the cytoskeleton and enriched in the neurite-like processes of cells, providing high intensity of the total signal. In addition, anchoring limits the diffusion of the sensor, enabling spatiotemporally resolved monitoring of subcellular variations in enzyme activity. Thus, anchoring is an important aspect to consider when designing FRET sensors for deeper understanding of cell signaling. PMID- 27196901 TI - In Vitro Activity of Copper(II) Complexes, Loaded or Unloaded into a Nanostructured Lipid System, against Mycobacterium tuberculosis. AB - Tuberculosis (TB) is an infectious disease caused mainly by the bacillus Mycobacterium tuberculosis (Mtb), presenting 9.5 million new cases and 1.5 million deaths in 2014. The aim of this study was to evaluate a nanostructured lipid system (NLS) composed of 10% phase oil (cholesterol), 10% surfactant (soy phosphatidylcholine, sodium oleate), and Eumulgin((r)) HRE 40 ([castor oil polyoxyl-40-hydrogenated] in a proportion of 3:6:8), and an 80% aqueous phase (phosphate buffer pH = 7.4) as a tactic to enhance the in vitro anti-Mtb activity of the copper(II) complexes [CuCl2(INH)2].H2O (1), [Cu(NCS)2(INH)2].5H2O (2) and [Cu(NCO)2(INH)2].4H2O (3). The Cu(II) complex-loaded NLS displayed sizes ranging from 169.5 +/- 0.7095 to 211.1 +/- 0.8963 nm, polydispersity index (PDI) varying from 0.135 +/- 0.0130 to 0.236 +/- 0.00100, and zeta potential ranging from 0.00690 +/- 0.0896 to -8.43 +/- 1.63 mV. Rheological analysis showed that the formulations behave as non-Newtonian fluids of the pseudoplastic and viscoelastic type. Antimycobacterial activities of the free complexes and NLS-loaded complexes against Mtb H37Rv ATCC 27294 were evaluated by the REMA methodology, and the selectivity index (SI) was calculated using the cytotoxicity index (IC50) against Vero (ATCC((r)) CCL-81), J774A.1 (ATCC((r)) TIB-67), and MRC-5 (ATCC((r)) CCL 171) cell lines. The data suggest that the incorporation of the complexes into NLS improved the inhibitory action against Mtb by 52-, 27-, and 4.7-fold and the SI values by 173-, 43-, and 7-fold for the compounds 1, 2 and 3, respectively. The incorporation of the complexes 1, 2 and 3 into the NLS also resulted in a significant decrease of toxicity towards an alternative model (Artemia salina L.). These findings suggest that the NLS may be considered as a platform for incorporation of metallic complexes aimed at the treatment of TB. PMID- 27196903 TI - Kinect-Based Virtual Game for the Elderly that Detects Incorrect Body Postures in Real Time. AB - Poor posture can result in loss of physical function, which is necessary to preserving independence in later life. Its decline is often the determining factor for loss of independence in the elderly. To avoid this, a system to correct poor posture in the elderly, designed for Kinect-based indoor applications, is proposed in this paper. Due to the importance of maintaining a healthy life style in senior citizens, the system has been integrated into a game which focuses on their physical stimulation. The game encourages users to perform physical activities while the posture correction system helps them to adopt proper posture. The system captures limb node data received from the Kinect sensor in order to detect posture variations in real time. The DTW algorithm compares the original posture with the current one to detect any deviation from the original correct position. The system was tested and achieved a successful detection percentage of 95.20%. Experimental tests performed in a nursing home with different users show the effectiveness of the proposed solution. PMID- 27196904 TI - Xurography as a Rapid Fabrication Alternative for Point-of-Care Devices: Assessment of Passive Micromixers. AB - Despite the copious amount of research on the design and operation of micromixers, there are few works regarding manufacture technology aimed at implementation beyond academic environments. This work evaluates the viability of xurography as a rapid fabrication tool for the development of ultra-low cost microfluidic technology for extreme Point-of-Care (POC) micromixing devices. By eschewing photolithographic processes and the bulkiness of pumping and enclosure systems for rapid fabrication and passively driven operation, xurography is introduced as a manufacturing alternative for asymmetric split and recombine (ASAR) micromixers. A T-micromixer design was used as a reference to assess the effects of different cutting conditions and materials on the geometric features of the resulting microdevices. Inspection by stereographic and confocal microscopy showed that it is possible to manufacture devices with less than 8% absolute dimensional error. Implementation of the manufacturing methodology in modified circular shape- based SAR microdevices (balanced and unbalanced configurations) showed that, despite the precision limitations of the xurographic process, it is possible to implement this methodology to produce functional micromixing devices. Mixing efficiency was evaluated numerically and experimentally at the outlet of the microdevices with performances up to 40%. Overall, the assessment encourages further research of xurography for the development of POC micromixers. PMID- 27196905 TI - A Novel Method for Proximity Detection of Moving Targets Using a Large-Scale Planar Capacitive Sensor System. AB - A novel method for proximity detection of moving targets (with high dielectric constants) using a large-scale (the size of each sensor is 31 cm * 19 cm) planar capacitive sensor system (PCSS) is proposed. The capacitive variation with distance is derived, and a pair of electrodes in a planar capacitive sensor unit (PCSU) with a spiral shape is found to have better performance on sensitivity distribution homogeneity and dynamic range than three other shapes (comb shape, rectangular shape, and circular shape). A driving excitation circuit with a Clapp oscillator is proposed, and a capacitance measuring circuit with sensitivity of 0.21 V p - p / pF is designed. The results of static experiments and dynamic experiments demonstrate that the voltage curves of static experiments are similar to those of dynamic experiments; therefore, the static data can be used to simulate the dynamic curves. The dynamic range of proximity detection for three projectiles is up to 60 cm, and the results of the following static experiments show that the PCSU with four neighboring units has the highest sensitivity (the sensitivities of other units are at least 4% lower); when the attack angle decreases, the intensity of sensor signal increases. This proposed method leads to the design of a feasible moving target detector with simple structure and low cost, which can be applied in the interception system. PMID- 27196906 TI - Ultra Wideband Indoor Positioning Technologies: Analysis and Recent Advances. AB - In recent years, indoor positioning has emerged as a critical function in many end-user applications; including military, civilian, disaster relief and peacekeeping missions. In comparison with outdoor environments, sensing location information in indoor environments requires a higher precision and is a more challenging task in part because various objects reflect and disperse signals. Ultra WideBand (UWB) is an emerging technology in the field of indoor positioning that has shown better performance compared to others. In order to set the stage for this work, we provide a survey of the state-of-the-art technologies in indoor positioning, followed by a detailed comparative analysis of UWB positioning technologies. We also provide an analysis of strengths, weaknesses, opportunities, and threats (SWOT) to analyze the present state of UWB positioning technologies. While SWOT is not a quantitative approach, it helps in assessing the real status and in revealing the potential of UWB positioning to effectively address the indoor positioning problem. Unlike previous studies, this paper presents new taxonomies, reviews some major recent advances, and argues for further exploration by the research community of this challenging problem space. PMID- 27196907 TI - A Plasmonic Temperature-Sensing Structure Based on Dual Laterally Side-Coupled Hexagonal Cavities. AB - A plasmonic temperature-sensing structure, based on a metal-insulator-metal (MIM) waveguide with dual side-coupled hexagonal cavities, is proposed and numerically investigated by using the finite-difference time-domain (FDTD) method in this paper. The numerical simulation results show that a resonance dip appears in the transmission spectrum. Moreover, the full width of half maximum (FWHM) of the resonance dip can be narrowed down, and the extinction ratio can reach a maximum value by tuning the coupling distance between the waveguide and two cavities. Based on a linear relationship between the resonance dip and environment temperature, the temperature-sensing characteristics are discussed. The temperature sensitivity is influenced by the side length and the coupling distance. Furthermore, for the first time, two concepts-optical spectrum interference (OSI) and misjudge rate (MR)-are introduced to study the temperature sensing resolution based on spectral interrogation. This work has some significance in the design of nanoscale optical sensors with high temperature sensitivity and a high sensing resolution. PMID- 27196908 TI - Methods and Best Practice to Intercompare Dissolved Oxygen Sensors and Fluorometers/Turbidimeters for Oceanographic Applications. AB - In European seas, ocean monitoring strategies in terms of key parameters, space and time scale vary widely for a range of technical and economic reasons. Nonetheless, the growing interest in the ocean interior promotes the investigation of processes such as oxygen consumption, primary productivity and ocean acidity requiring that close attention is paid to the instruments in terms of measurement setup, configuration, calibration, maintenance procedures and quality assessment. To this aim, two separate hardware and software tools were developed in order to test and simultaneously intercompare several oxygen probes and fluorometers/turbidimeters, respectively in the same environmental conditions, with a configuration as close as possible to real in-situ deployment. The chamber designed to perform chlorophyll-a and turbidity tests allowed for the simultaneous acquisition of analogue and digital signals of several sensors at the same time, so it was sufficiently compact to be used in both laboratory and onboard vessels. Methodologies and best practice committed to the intercomparison of dissolved oxygen sensors and fluorometers/turbidimeters have been used, which aid in the promotion of interoperability to access key infrastructures, such as ocean observatories and calibration facilities. Results from laboratory tests as well as field tests in the Mediterranean Sea are presented. PMID- 27196909 TI - State of the Art in LP-WAN Solutions for Industrial IoT Services. AB - The emergence of low-cost connected devices is enabling a new wave of sensorization services. These services can be highly leveraged in industrial applications. However, the technologies employed so far for managing this kind of system do not fully cover the strict requirements of industrial networks, especially those regarding energy efficiency. In this article a novel paradigm, called Low-Power Wide Area Networking (LP-WAN), is explored. By means of a cellular-type architecture, LP-WAN-based solutions aim at fulfilling the reliability and efficiency challenges posed by long-term industrial networks. Thus, the most prominent LP-WAN solutions are reviewed, identifying and discussing the pros and cons of each of them. The focus is also on examining the current deployment state of these platforms in Spain. Although LP-WAN systems are at early stages of development, they represent a promising alternative for boosting future industrial IIoT (Industrial Internet of Things) networks and services. PMID- 27196910 TI - Reduction of Motion Artifacts and Improvement of R Peak Detecting Accuracy Using Adjacent Non-Intrusive ECG Sensors. AB - Non-intrusive electrocardiogram (ECG) monitoring has many advantages: easy to measure and apply in daily life. However, motion noise in the measured signal is the major problem of non-intrusive measurement. This paper proposes a method to reduce the noise and to detect the R peaks of ECG in a stable manner in a sitting arrangement using non-intrusive sensors. The method utilizes two capacitive ECG sensors (cECGs) to measure ECG, and another two cECGs located adjacent to the sensors for ECG are added to obtain the information on motion. Then, active noise cancellation technique and the motion information are used to reduce motion noise. To verify the proposed method, ECG was measured indoors and during driving, and the accuracy of the detected R peaks was compared. After applying the method, the sum of sensitivity and positive predictivity increased 8.39% on average and 26.26% maximally in the data. Based on the results, it was confirmed that the motion noise was reduced and that more reliable R peak positions could be obtained by the proposed method. The robustness of the new ECG measurement method will elicit benefits to various health care systems that require noninvasive heart rate or heart rate variability measurements. PMID- 27196911 TI - Field-Based Optimal Placement of Antennas for Body-Worn Wireless Sensors. AB - We investigate a case of automated energy-budget-aware optimization of the physical position of nodes (sensors) in a Wireless Body Area Network (WBAN). This problem has not been presented in the literature yet, as opposed to antenna and routing optimization, which are relatively well-addressed. In our research, which was inspired by a safety-critical application for firefighters, the sensor network consists of three nodes located on the human body. The nodes communicate over a radio link operating in the 2.4 GHz or 5.8 GHz ISM frequency band. Two sensors have a fixed location: one on the head (earlobe pulse oximetry) and one on the arm (with accelerometers, temperature and humidity sensors, and a GPS receiver), while the position of the third sensor can be adjusted within a predefined region on the wearer's chest. The path loss between each node pair strongly depends on the location of the nodes and is difficult to predict without performing a full-wave electromagnetic simulation. Our optimization scheme employs evolutionary computing. The novelty of our approach lies not only in the formulation of the problem but also in linking a fully automated optimization procedure with an electromagnetic simulator and a simplified human body model. This combination turns out to be a computationally effective solution, which, depending on the initial placement, has a potential to improve performance of our example sensor network setup by up to about 20 dB with respect to the path loss between selected nodes. PMID- 27196912 TI - A Mobile and Low-Cost System for Environmental Monitoring: A Case Study. AB - Northern Italy has one of the highest air pollution levels in the European Union. This paper describes a mobile wireless sensor network system intended to complement the already existing official air quality monitoring systems of the metropolitan town of Torino. The system is characterized by a high portability and low cost, in both acquisition and maintenance. The high portability of the system aims to improve the spatial distribution and resolution of the measurements from the official static monitoring stations. Commercial PM 10 and O 3 sensors were incorporated into the system and were subsequently tested in a controlled environment and in the field. The test in the field, performed in collaboration with the local environmental agency, revealed that the sensors can provide accurate data if properly calibrated and maintained. Further tests were carried out by mounting the system on bicycles in order to increase their mobility. PMID- 27196913 TI - Tools to Perform Local Dense 3D Reconstruction of Shallow Water Seabed. AB - Tasks such as distinguishing or identifying individual objects of interest require the production of dense local clouds at the scale of these individual objects of interest. Due to the physical and dynamic properties of an underwater environment, the usual dense matching algorithms must be rethought in order to be adaptive. These properties also imply that the scene must be observed at close range. Classic robotized acquisition systems are oversized for local studies in shallow water while the systematic acquisition of data is not guaranteed with divers. We address these two major issues through a multidisciplinary approach. To efficiently acquire on-demand stereoscopic pairs using simple logistics in small areas of shallow water, we devised an agile light-weight dedicated system which is easy to reproduce. To densely match two views in a reliable way, we devised a reconstruction algorithm that automatically accounts for the dynamics, variability and light absorption of the underwater environment. Field experiments in the Mediterranean Sea were used to assess the results. PMID- 27196914 TI - How Efficient Is My (Medicinal) Chemistry? AB - "Greening" a chemical transformation is not about only changing the nature of a solvent or decreasing the reaction temperature. There are metrics enabling a critical quantification of the efficiency of an experimental protocol. Some of them are applied to different sequences for the preparation of paracetamol in order to understand their performance parameters and elucidate pathways for improvement. PMID- 27196917 TI - Orange Is the New Green: Exploring the Restorative Capacity of Seasonal Foliage in Schoolyard Trees. AB - Urban schoolyard environments are increasingly characterized by a proliferation of hard surfaces with little if any greenery. Schoolyard "greening" initiatives are becoming increasingly popular; however, schoolyard designs often fail to realize their restorative potential. In this quasi-experimental study, a proposed schoolyard greening project was used to visualize alternative planting designs and seasonal tree foliage; these design alternatives were subsequently used as visual stimuli in a survey administered to children who will use the schoolyard to assess the perceived restorative capacity of different design features. The findings indicate that seasonal changes in tree foliage enhance the perceived restorative quality of schoolyard environments. Specifically, fall foliage colour, when compared to green foliage, is rated as being perceived to be equally restorative for children. Additionally, seasonal planting, including evergreen conifers, may enhance the restorative quality of the schoolyard especially when deciduous trees are leafless. Landscape design professionals, community-based organizations, and other decision-makers in schoolyard greening efforts should strategically consider their tree choices to maximize year-round support for healthy attention functioning in children through restoration. PMID- 27196915 TI - Tiny Microbes with a Big Impact: The Role of Cyanobacteria and Their Metabolites in Shaping Our Future. AB - Cyanobacteria are among the first microorganisms to have inhabited the Earth. Throughout the last few billion years, they have played a major role in shaping the Earth as the planet we live in, and they continue to play a significant role in our everyday lives. Besides being an essential source of atmospheric oxygen, marine cyanobacteria are prolific secondary metabolite producers, often despite the exceptionally small genomes. Secondary metabolites produced by these organisms are diverse and complex; these include compounds, such as pigments and fluorescent dyes, as well as biologically-active compounds with a particular interest for the pharmaceutical industry. Cyanobacteria are currently regarded as an important source of nutrients and biofuels and form an integral part of novel innovative energy-efficient designs. Being autotrophic organisms, cyanobacteria are well suited for large-scale biotechnological applications due to the low requirements for organic nutrients. Recent advances in molecular biology techniques have considerably enhanced the potential for industries to optimize the production of cyanobacteria secondary metabolites with desired functions. This manuscript reviews the environmental role of marine cyanobacteria with a particular focus on their secondary metabolites and discusses current and future developments in both the production of desired cyanobacterial metabolites and their potential uses in future innovative projects. PMID- 27196919 TI - Boiling over: A Descriptive Analysis of Drinking Water Advisories in First Nations Communities in Ontario, Canada. AB - Access to safe and reliable drinking water is commonplace for most Canadians. However, the right to safe and reliable drinking water is denied to many First Nations peoples across the country, highlighting a priority public health and environmental justice issue in Canada. This paper describes trends and characteristics of drinking water advisories, used as a proxy for reliable access to safe drinking water, among First Nations communities in the province of Ontario. Visual and statistical tools were used to summarize the advisory data in general, temporal trends, and characteristics of the drinking water systems in which advisories were issued. Overall, 402 advisories were issued during the study period. The number of advisories increased from 25 in 2004 to 75 in 2013. The average advisory duration was 294 days. Most advisories were reported in summer months and equipment malfunction was the most commonly reported reason for issuing an advisory. Nearly half of all advisories occurred in drinking water systems where additional operator training was needed. These findings underscore that the prevalence of drinking water advisories in First Nations communities is a problem that must be addressed. Concerted and multi-faceted efforts are called for to improve the provision of safe and reliable drinking water First Nations communities. PMID- 27196916 TI - "The Good, the Bad and the Ugly" of Chitosans. AB - The objective of this paper is to emphasize the fact that while consistent interest has been paid to the industrial use of chitosan, minor attention has been devoted to spread the knowledge of a good characterization of its physico chemical properties. Therefore, the paper attempts to critically comment on the conflicting experimental results, highlighting the facts, the myths and the controversies. The goal is to indicate how to take advantage of chitosan versatility, to learn how to manage its variability and show how to properly tackle some unexpected undesirable features. In the sections of the paper various issues that relate chitosan properties to some basic features and to advanced solutions and applications are presented. The introduction outlines some historical pioneering works, where the chemistry of chitosan was originally explored. Thereafter, particular reference is made to analytical purity, characterization and chain modifications. The macromolecular characterization is mostly related to molecular weight and to degree of acetylation, but also refers to the conformational and rheological properties and solution stability. Then, the antimicrobial activity of chitosan in relation with its solubility is reviewed. A section is dedicated to the formulation of chitosan biomaterials, from gel to nanobeads, exploring their innovative application as active carrier nanoparticles. Finally, the toxicity issue of chitosan as a polymer and as a constructed nanomaterial is briefly commented in the conclusions. PMID- 27196918 TI - Prevalence and Factors Associated with Substance Use and Misuse among Kosovar Adolescents; Cross Sectional Study of Scholastic, Familial-, and Sports-Related Factors of Influence. AB - Adolescence is considered to be the most important period for the prevention of substance use and misuse (SUM). The aim of this study was to investigate the problem of SUM and to establish potentially important factors associated with SUM in Kosovar adolescents. Multi-stage simple random sampling was used to select participants. At the end of their high school education, 980 adolescents (623 females) ages 17 to 19 years old were enrolled in the study. The prevalence of smoking, alcohol consumption (measured by Alcohol Use Disorder Identification Test-AUDIT), and illegal drug use (dependent variables), as well as socio demographic, scholastic, familial, and sports-related factors (independent variables), were assessed. Boys smoke cigarettes more often than girls with daily smoking prevalence of 16% among boys and 9% among girls (OR = 1.85, 95% = CI 1.25 2.75). The prevalence of harmful drinking (i.e., AUDIT scores of >10) is found to be alarming (41% and 37% for boys and girls, respectively; OR = 1.13, 95% CI = 0.87-1.48), while 17% of boys and 9% of girls used illegal drugs (OR = 2.01, 95% CI = 1.35-2.95). The behavioral grade (observed as: excellent-average-poor) is the factor that was most significantly correlated with SUM both in boys and girls, with lower behavioral grades among those adolescents who consume substances. In girls, lower maternal education levels were associated with a decreased likelihood of SUM, whereas sports achievement was negatively associated with risky drinking. In boys, sports achievement decreased the likelihood of daily smoking. Information on the factors associated with SUM should be disseminated among sports and school authorities. PMID- 27196920 TI - Contributing Factors to Colorectal Cancer Screening among Chinese People: A Review of Quantitative Studies. AB - Colorectal cancer (CRC) is a major health problem in Asia. It has been reported that the Chinese are more susceptible to CRC than many other ethnic groups. Screening for CRC is a cost-effective prevention and control strategy; however, the screening rates among the Chinese are sub-optimal. We conducted a review to identify the factors associated with CRC screening participation among Chinese people. Twenty-two studies that examined the factors related to CRC screening behaviors among the Chinese were identified through five databases. Seven factors were consistently reported to influence CRC screening behaviors in at least one of the studies: socio-demographic characteristics (educational level, health insurance, and knowledge about CRC and its screening); psychological factors (perceived severity of CRC, susceptibility of having CRC, and barriers to screening); and contact with medical provider (physician recommendation). The evidence base for many of these relationships is quite limited. Furthermore, the associations of many factors, including age, gender, income, cancer worry/fear, and self-efficacy with CRC screening behaviors, were mixed or inconsistent across these studies, thereby indicating that more studies are needed in this area. PMID- 27196921 TI - Unequal Recovery? Federal Resource Distribution after a Midwest Flood Disaster. AB - Following severe flooding in 2008, three Iowa communities acquired over 1000 damaged properties to support disaster recovery and mitigation. This research applies a distributive justice framework to analyze the distribution of disaster recovery funds for property acquisition. Two research questions drive the analysis: (1) how does recovery vary by acquisition funding source; and (2) what is the relationship between recovery and vulnerable populations? Through spatial econometric modeling, relative recovery is compared between two federal programs that funded the acquisitions, and across socially vulnerable populations. The results indicate both distributive and temporal inequalities in the allocation of federal recovery funds. In particular, Latino and elderly populations were associated with lower recovery rates. Recommendations for future research in flood recovery and acquisitions are provided. PMID- 27196922 TI - Which Factors Determine Metal Accumulation in Agricultural Soils in the Severely Human-Coupled Ecosystem? AB - Agricultural soil is typically an important component of urban ecosystems, contributing directly or indirectly to the general quality of human life. To understand which factors influence metal accumulation in agricultural soils in urban ecosystems is becoming increasingly important. Land use, soil type and urbanization indicators all account for considerable differences in metal accumulation in agricultural soils, and the interactions between these factors on metal concentrations were also examined. Results showed that Zn, Cu, and Cd concentrations varied significantly among different land use types. Concentrations of all metals, except for Cd, were higher in calcareous cinnamon soil than in fluvo-aquic soil. Expansion distance and road density were adopted as urbanization indicators, and distance from the urban center was significantly negatively correlated with concentrations of Hg, and negatively correlated with concentrations of Zn, and road density was positively correlated with Cd concentrations. Multivariate analysis of variance indicated that Hg concentration was significantly influenced by the four-way interaction among all factors. The results in this study provide basic data to support the management of agricultural soils and to help policy makers to plan ahead in Beijing. PMID- 27196923 TI - The Effect of MicroRNA bantam on Baculovirus AcMNPV Infection in Vitro and in Vivo. AB - The role of microRNA bantam, one of the most abundant microRNAs in Sf9 cells, was studied for its role in baculovirus infection in vitro and in vivo. The expression level of bantam was increased after AcMNPV infection in Sf9 cells and in Spodoptera litura larvae. In Sf9 cells, application of bantam inhibitor or mimic altered the expression of many virus genes, the most affected gene being lef8, gp41 and p10, the expression level of which was increased by 8, 10 and 40 times, respectively, in the presence of bantam inhibitor. Virus DNA replication was decreased in the presence of bantam mimic and increased in the presence of bantam inhibitor in a dose dependent manner. However, the production of budded virus did not change significantly. Feeding the larvae of S. litura and Spodoptera exigua with bantam antagomiR, a more stable form of the inhibitor, resulted in an abnormal larval growth and a decreased pupation rate. In S. litura, larvae died 3.5 days sooner than the control when bantam antagomiR was applied, together with AcMNPV. In infected S. exigua, larval mortality increased from 47% without antagomiR to 80% with it. The results suggest that microRNA bantam plays an important role in insect growth, as well as in baculovirus-insect interaction. PMID- 27196924 TI - Persistent Inequalities in Child Undernutrition in Cambodia from 2000 until Today. AB - The study assessed the trends of nutritional status of children under age five in Cambodia over four DHS surveys from 2000 to 2014 and the contribution of socioeconomic and demographic factors to its changes. Undernutrition was a public health problem in all surveys. Despite consistent improvement over the years, stunting still affected 32.5% of children in 2014. Wasting prevalence did not improve since 2005 and affected 9.6% of children under five in 2014. Low wealth and mother education; and rural residence contributed to undernutrition. In 2014; wealth status was the main socioeconomic factor associated with undernutrition and the nutritional status of children was strongly related to that of their mothers. Anemia prevalence was high and after a decrease between 2000 and 2005 remained at 45%. The prevalence of overweight was less than 10% and did not change over the years despite an increasing trend in the richest households of urban areas. Persistent inequalities in child undernutrition call for action, giving priority to the most vulnerable households to ensure availability and access to nutrient-rich foods for women and children through nutrition-sensitive and nutrition-specific programs. The recent increase of overweight in the richest populations must also be considered in Cambodian health policies. PMID- 27196925 TI - Adequate Iodine Status in New Zealand School Children Post-Fortification of Bread with Iodised Salt. AB - Iodine deficiency re-emerged in New Zealand in the 1990s, prompting the mandatory fortification of bread with iodised salt from 2009. This study aimed to determine the iodine status of New Zealand children when the fortification of bread was well established. A cross-sectional survey of children aged 8-10 years was conducted in the cities of Auckland and Christchurch, New Zealand, from March to May 2015. Children provided a spot urine sample for the determination of urinary iodine concentration (UIC), a fingerpick blood sample for Thyroglobulin (Tg) concentration, and completed a questionnaire ascertaining socio-demographic information that also included an iodine-specific food frequency questionnaire (FFQ). The FFQ was used to estimate iodine intake from all main food sources including bread and iodised salt. The median UIC for all children (n = 415) was 116 MUg/L (females 106 MUg/L, males 131 MUg/L) indicative of adequate iodine status according to the World Health Organisation (WHO, i.e., median UIC of 100 199 MUg/L). The median Tg concentration was 8.7 MUg/L, which was <10 MUg/L confirming adequate iodine status. There was a significant difference in UIC by sex (p = 0.001) and ethnicity (p = 0.006). The mean iodine intake from the food only model was 65 MUg/day. Bread contributed 51% of total iodine intake in the food-only model, providing a mean iodine intake of 35 MUg/day. The mean iodine intake from the food-plus-iodised salt model was 101 MUg/day. In conclusion, the results of this study confirm that the iodine status in New Zealand school children is now adequate. PMID- 27196926 TI - Degradation of Swainsonine by the NADP-Dependent Alcohol Dehydrogenase A1R6C3 in Arthrobacter sp. HW08. AB - Swainsonine is an indolizidine alkaloid that has been found in locoweeds and some fungi. Our previous study demonstrated that Arthrobacter sp. HW08 or its crude enzyme extract could degrade swainsonie efficiently. However, the mechanism of swainsonine degradation in bacteria remains unclear. In this study, we used label free quantitative proteomics method based on liquid chromatography-electrospray ionization-tandem mass spectrometry to dissect the mechanism of swainsonine biodegradation by Arthrobacter sp. HW08. The results showed that 129 differentially expressed proteins were relevant to swainsonine degradation. These differentially expressed proteins were mostly related to the biological process of metabolism and the molecular function of catalytic activity. Among the 129 differentially expressed proteins, putative sugar phosphate isomerase/epimerase A1R5X7, Acetyl-CoA acetyltransferase A0JZ95, and nicotinamide adenine dinucleotide phosphate (NADP)-dependent alcohol dehydrogenase A1R6C3 were found to contribute to the swainsonine degradation. Notably, NADP-dependent alcohol dehyrodgenase A1R6C3 appeared to play a major role in degrading swainsonine, but not as much as Arthrobacter sp. HW08 did. Collectively, our findings here provide insights to understand the mechanism of swainsonine degradation in bacteria. PMID- 27196927 TI - Botulinum Neurotoxin Serotype A Recognizes Its Protein Receptor SV2 by a Different Mechanism than Botulinum Neurotoxin B Synaptotagmin. AB - Botulinum neurotoxins (BoNTs) exhibit extraordinary potency due to their exquisite neurospecificity, which is achieved by dual binding to complex polysialo-gangliosides and synaptic vesicle proteins. The luminal domain 4 (LD4) of the three synaptic vesicle glycoprotein 2 isoforms, SV2A-C, identified as protein receptors for the most relevant serotype BoNT/A, binds within the 50 kDa cell binding domain HC of BoNT/A. Here, we deciphered the BoNT/A-SV2 interactions in more detail. In pull down assays, the binding of HCA to SV2-LD4 isoforms decreases from SV2C >> SV2A > SV2B. A binding constant of 200 nM was determined for BoNT/A to rat SV2C-LD4 in GST pull down assay. A similar binding constant was determined by surface plasmon resonance for HCA to rat SV2C and to human SV2C, the latter being slightly lower due to the substitution L563F in LD4. At pH 5, as measured in acidic synaptic vesicles, the binding constant of HCA to hSV2C is increased more than 10-fold. Circular dichroism spectroscopy reveals that the quadrilateral helix of SV2C-LD4 already exists in solution prior to BoNT/A binding. Hence, the BoNT/A-SV2C interaction is of different nature compared to BoNT/B-Syt-II. In particular, the preexistence of the quadrilateral beta-sheet helix of SV2 and its pH-dependent binding to BoNT/A via backbone-backbone interactions constitute major differences. Knowledge of the molecular details of BoNT/A-SV2 interactions drives the development of high affinity peptides to counteract BoNT/A intoxications or to capture functional BoNT/A variants in innovative detection systems for botulism diagnostic. PMID- 27196931 TI - The Landscape of the Emergence of Life. AB - Is it unrealistic to presuppose that all of the steps that could lead to the formation of life could occur in one setting?[...]. PMID- 27196932 TI - Real-Time Monitoring and Evaluation of a Visual-Based Cervical Cancer Screening Program Using a Decision Support Job Aid. AB - In many developing nations, cervical cancer screening is done by visual inspection with acetic acid (VIA). Monitoring and evaluation (M&E) of such screening programs is challenging. An enhanced visual assessment (EVA) system was developed to augment VIA procedures in low-resource settings. The EVA System consists of a mobile colposcope built around a smartphone, and an online image portal for storing and annotating images. A smartphone app is used to control the mobile colposcope, and upload pictures to the image portal. In this paper, a new app feature that documents clinical decisions using an integrated job aid was deployed in a cervical cancer screening camp in Kenya. Six organizations conducting VIA used the EVA System to screen 824 patients over the course of a week, and providers recorded their diagnoses and treatments in the application. Real-time aggregated statistics were broadcast on a public website. Screening organizations were able to assess the number of patients screened, alongside treatment rates, and the patients who tested positive and required treatment in real time, which allowed them to make adjustments as needed. The real-time M&E enabled by "smart" diagnostic medical devices holds promise for broader use in screening programs in low-resource settings. PMID- 27196930 TI - Transcriptome-Wide Survey and Expression Profile Analysis of Putative Chrysanthemum HD-Zip I and II Genes. AB - The homeodomain-leucine zipper (HD-Zip) transcription factor family is a key transcription factor family and unique to the plant kingdom. It consists of a homeodomain and a leucine zipper that serve in combination as a dimerization motif. The family can be classified into four subfamilies, and these subfamilies participate in the development of hormones and mediation of hormone action and are involved in plant responses to environmental conditions. However, limited information on this gene family is available for the important chrysanthemum ornamental species (Chrysanthemum morifolium). Here, we characterized 17 chrysanthemum HD-Zip genes based on transcriptome sequences. Phylogenetic analyses revealed that 17 CmHB genes were distributed in the HD-Zip subfamilies I and II and identified two pairs of putative orthologous proteins in Arabidopsis and chrysanthemum and four pairs of paralogous proteins in chrysanthemum. The software MEME was used to identify 7 putative motifs with E values less than 1e-3 in the chrysanthemum HD-Zip factors, and they can be clearly classified into two groups based on the composition of the motifs. A bioinformatics analysis predicted that 8 CmHB genes could be targeted by 10 miRNA families, and the expression of these 17 genes in response to phytohormone treatments and abiotic stresses was characterized. The results presented here will promote research on the various functions of the HD-Zip gene family members in plant hormones and stress responses. PMID- 27196928 TI - ADAM and ADAMTS Family Proteins and Snake Venom Metalloproteinases: A Structural Overview. AB - A disintegrin and metalloproteinase (ADAM) family proteins constitute a major class of membrane-anchored multidomain proteinases that are responsible for the shedding of cell-surface protein ectodomains, including the latent forms of growth factors, cytokines, receptors and other molecules. Snake venom metalloproteinases (SVMPs) are major components in most viper venoms. SVMPs are primarily responsible for hemorrhagic activity and may also interfere with the hemostatic system in envenomed animals. SVMPs are phylogenetically most closely related to ADAMs and, together with ADAMs and related ADAM with thrombospondin motifs (ADAMTS) family proteinases, constitute adamalysins/reprolysins or the M12B clan (MEROPS database) of metalloproteinases. Although the catalytic domain structure is topologically similar to that of other metalloproteinases such as matrix metalloproteinases, the M12B proteinases have a modular structure with multiple non-catalytic ancillary domains that are not found in other proteinases. Notably, crystallographic studies revealed that, in addition to the conserved metalloproteinase domain, M12B members share a hallmark cysteine-rich domain designated as the "ADAM_CR" domain. Despite their name, ADAMTSs lack disintegrin like structures and instead comprise two ADAM_CR domains. This review highlights the current state of our knowledge on the three-dimensional structures of M12B proteinases, focusing on their unique domains that may collaboratively participate in directing these proteinases to specific substrates. PMID- 27196929 TI - Frizzled7: A Promising Achilles' Heel for Targeting the Wnt Receptor Complex to Treat Cancer. AB - Frizzled7 is arguably the most studied member of the Frizzled family, which are the cognate Wnt receptors. Frizzled7 is highly conserved through evolution, from Hydra through to humans, and is expressed in diverse organisms, tissues and human disease contexts. Frizzled receptors can homo- or hetero-polymerise and associate with several co-receptors to transmit Wnt signalling. Notably, Frizzled7 can transmit signalling via multiple Wnt transduction pathways and bind to several different Wnt ligands, Frizzled receptors and co-receptors. These promiscuous binding and functional properties are thought to underlie the pivotal role Frizzled7 plays in embryonic developmental and stem cell function. Recent studies have identified that Frizzled7 is upregulated in diverse human cancers, and promotes proliferation, progression and invasion, and orchestrates cellular transitions that underscore cancer metastasis. Importantly, Frizzled7 is able to regulate Wnt signalling activity even in cancer cells which have mutations to down-stream signal transducers. In this review we discuss the various aspects of Frizzled7 signalling and function, and the implications these have for therapeutic targeting of Frizzled7 in cancer. PMID- 27196935 TI - Astrocytic IL-6 Influences the Clinical Symptoms of EAE in Mice. AB - Interleukin-6 (IL-6) is a multifunctional cytokine that not only plays major roles in the immune system, but also serves as a coordinator between the nervous and endocrine systems. IL-6 is produced in multiple cell types in the CNS, and in turn, many cells respond to it. It is therefore important to ascertain which cell type is the key responder to IL-6 during both physiological and pathological conditions. In order to test the role of astrocytic IL-6 in neuroinflammation, we studied an extensively-used animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), in mice with an IL-6 deficiency in astrocytes (Ast-IL-6 KO). Results indicate that lack of astrocytic IL-6 did not cause major changes in EAE symptomatology. However, a delay in the onset of clinical signs was observed in Ast-IL-6 KO females, with fewer inflammatory infiltrates and decreased demyelination and some alterations in gliosis and vasogenesis, compared to floxed mice. These results suggest that astrocyte-secreted IL-6 has some roles in EAE pathogenesis, at least in females. PMID- 27196933 TI - Improving the Sensitivity and Functionality of Mobile Webcam-Based Fluorescence Detectors for Point-of-Care Diagnostics in Global Health. AB - Resource-poor countries and regions require effective, low-cost diagnostic devices for accurate identification and diagnosis of health conditions. Optical detection technologies used for many types of biological and clinical analysis can play a significant role in addressing this need, but must be sufficiently affordable and portable for use in global health settings. Most current clinical optical imaging technologies are accurate and sensitive, but also expensive and difficult to adapt for use in these settings. These challenges can be mitigated by taking advantage of affordable consumer electronics mobile devices such as webcams, mobile phones, charge-coupled device (CCD) cameras, lasers, and LEDs. Low-cost, portable multi-wavelength fluorescence plate readers have been developed for many applications including detection of microbial toxins such as C. Botulinum A neurotoxin, Shiga toxin, and S. aureus enterotoxin B (SEB), and flow cytometry has been used to detect very low cell concentrations. However, the relatively low sensitivities of these devices limit their clinical utility. We have developed several approaches to improve their sensitivity presented here for webcam based fluorescence detectors, including (1) image stacking to improve signal-to-noise ratios; (2) lasers to enable fluorescence excitation for flow cytometry; and (3) streak imaging to capture the trajectory of a single cell, enabling imaging sensors with high noise levels to detect rare cell events. These approaches can also help to overcome some of the limitations of other low-cost optical detection technologies such as CCD or phone-based detectors (like high noise levels or low sensitivities), and provide for their use in low-cost medical diagnostics in resource-poor settings. PMID- 27196937 TI - Mixed Matrix Membranes for O2/N2 Separation: The Influence of Temperature. AB - In this work, mixed matrix membranes (MMMs) composed of small-pore zeolites with various topologies (CHA (Si/Al = 5), LTA (Si/Al = 1 and 5), and Rho (Si/Al = 5)) as dispersed phase, and the hugely permeable poly(1-trimethylsilyl-1-propyne) (PTMSP) as continuous phase, have been synthesized via solution casting, in order to obtain membranes that could be attractive for oxygen-enriched air production. The O2/N2 gas separation performance of the MMMs has been analyzed in terms of permeability, diffusivity, and solubility in the temperature range of 298-333 K. The higher the temperature of the oxygen-enriched stream, the lower the energy required for the combustion process. The effect of temperature on the gas permeability, diffusivity, and solubility of these MMMs is described in terms of the Arrhenius and Van't Hoff relationships with acceptable accuracy. Moreover, the O2/N2 permselectivity of the MMMs increases with temperature, the O2/N2 selectivities being considerably higher than those of the pure PTMSP. In consequence, most of the MMMs prepared in this work exceeded the Robeson's upper bound for the O2/N2 gas pair in the temperature range under study, with not much decrease in the O2 permeabilities, reaching O2/N2 selectivities of up to 8.43 and O2 permeabilities up to 4,800 Barrer at 333 K. PMID- 27196934 TI - Comparison of Surface Proteomes of Adherence Variants of Listeria Monocytogenes Using LC-MS/MS for Identification of Potential Surface Adhesins. AB - The ability of Listeria monocytogenes to adhere and form biofilms leads to persistence in food processing plants and food-associated listeriosis. The role of specific surface proteins as adhesins to attach Listeria cells to various contact surfaces has not been well characterized to date. In prior research comparing different methods for surface protein extraction, the Ghost urea method revealed cleaner protein content as verified by the least cytoplasmic protein detected in surface extracts using LC-MS/MS. The same technique was utilized to extract and detect surface proteins among two surface-adherent phenotypic strains of L. monocytogenes (i.e., strongly and weakly adherent). Of 640 total proteins detected among planktonic and sessile cells, 21 protein members were exclusively detected in the sessile cells. Relative LC-MS/MS detection and quantification of surface-extracted proteins from the planktonic weakly adherent (CW35) and strongly adherent strains (99-38) were examined by protein mass normalization of proteins. We found that L. monocytogenes 99-38 exhibited a total of 22 surface proteins that were over-expressed: 11 proteins were detected in surface extracts of both sessile and planktonic 99-38 that were >=5-fold over-expressed while another 11 proteins were detected only in planktonic 99-38 cells that were >=10 fold over-expressed. Our results suggest that these protein members are worthy of further investigation for their involvement as surface adhesins. PMID- 27196936 TI - Antioxidant Cerium Oxide Nanoparticles in Biology and Medicine. AB - Previously, catalytic cerium oxide nanoparticles (CNPs, nanoceria, CeO2-x NPs) have been widely utilized for chemical mechanical planarization in the semiconductor industry and for reducing harmful emissions and improving fuel combustion efficiency in the automobile industry. Researchers are now harnessing the catalytic repertoire of CNPs to develop potential new treatment modalities for both oxidative- and nitrosative-stress induced disorders and diseases. In order to reach the point where our experimental understanding of the antioxidant activity of CNPs can be translated into useful therapeutics in the clinic, it is necessary to evaluate the most current evidence that supports CNP antioxidant activity in biological systems. Accordingly, the aims of this review are three fold: (1) To describe the putative reaction mechanisms and physicochemical surface properties that enable CNPs to both scavenge reactive oxygen species (ROS) and to act as antioxidant enzyme-like mimetics in solution; (2) To provide an overview, with commentary, regarding the most robust design and synthesis pathways for preparing CNPs with catalytic antioxidant activity; (3) To provide the reader with the most up-to-date in vitro and in vivo experimental evidence supporting the ROS-scavenging potential of CNPs in biology and medicine. PMID- 27196938 TI - Controlled Bulk Properties of Composite Polymeric Solutions for Extensive Structural Order of Honeycomb Polysulfone Membranes. AB - This work provides additional insights into the identification of operating conditions necessary to overcome a current limitation to the scale-up of the breath figure method, which is regarded as an outstanding manufacturing approach for structurally ordered porous films. The major restriction concerns, indeed, uncontrolled touching droplets at the boundary. Herein, the bulk of polymeric solutions are properly managed to generate honeycomb membranes with a long-range structurally ordered texture. Water uptake and dynamics are explored as chemical environments are changed with the intent to modify the hydrophilic/hydrophobic balance and local water floatation. In this context, a model surfactant such as the polyoxyethylene sorbitan monolaurate is used in combination with alcohols at different chain length extents and a traditional polymer such as the polyethersufone. Changes in the interfacial tension and kinematic viscosity taking place in the bulk of composite solutions are explored and examined in relation to competitive droplet nucleation and growth rate. As a result, extensive structurally ordered honeycomb textures are obtained with the rising content of the surfactant while a broad range of well-sized pores is targeted as a function of the hydrophilic-hydrophobic balance and viscosity of the composite polymeric mixture. The experimental findings confirm the consistency of the approach and are expected to give propulsion to the commercially production of breath figures films shortly. PMID- 27196941 TI - Announcement: Click It or Ticket Campaign - May 23-June 5, 2016. AB - Click It or Ticket is a national campaign coordinated annually by the National Highway Traffic Safety Administration to increase the proper use of seat belts. In 2014, more than 21,000 passenger vehicle occupants died in motor vehicle crashes in the United States; 49% were unrestrained at the time of the crash (1). An additional 2.4 million occupants (restrained and unrestrained) were treated in emergency departments for nonfatal crash-related injuries (2). PMID- 27196939 TI - Genetic Approaches to Study Plant Responses to Environmental Stresses: An Overview. AB - The assessment of gene expression levels is an important step toward elucidating gene functions temporally and spatially. Decades ago, typical studies were focusing on a few genes individually, whereas now researchers are able to examine whole genomes at once. The upgrade of throughput levels aided the introduction of systems biology approaches whereby cell functional networks can be scrutinized in their entireties to unravel potential functional interacting components. The birth of systems biology goes hand-in-hand with huge technological advancements and enables a fairly rapid detection of all transcripts in studied biological samples. Even so, earlier technologies that were restricted to probing single genes or a subset of genes still have their place in research laboratories. The objective here is to highlight key approaches used in gene expression analysis in plant responses to environmental stresses, or, more generally, any other condition of interest. Northern blots, RNase protection assays, and qPCR are described for their targeted detection of one or a few transcripts at a once. Differential display and serial analysis of gene expression represent non targeted methods to evaluate expression changes of a significant number of gene transcripts. Finally, microarrays and RNA-seq (next-generation sequencing) contribute to the ultimate goal of identifying and quantifying all transcripts in a cell under conditions or stages of study. Recent examples of applications as well as principles, advantages, and drawbacks of each method are contrasted. We also suggest replacing the term "Next-Generation Sequencing (NGS)" with another less confusing synonym such as "RNA-seq", "high throughput sequencing", or "massively parallel sequencing" to avoid confusion with any future sequencing technologies. PMID- 27196942 TI - Regenerative therapy for vestibular disorders using human induced pluripotent stem cells (iPSCs): neural differentiation of human iPSC-derived neural stem cells after in vitro transplantation into mouse vestibular epithelia. AB - OBJECTIVES: Vestibular ganglion cells, which convey sense of motion from vestibular hair cells to the brainstem, are known to degenerate with aging and after vestibular neuritis. Thus, regeneration of vestibular ganglion cells is important to aid in the recovery of balance for associated disorders. METHODS: The present study derived hNSCs from induced pluripotent stem cells (iPSCs) and transplanted these cells into mouse utricle tissues. After a 7-day co-culture period, histological and electrophysiological examinations of transplanted hNSCs were performed. RESULTS: Injected hNSC-derived cells produced elongated axon-like structures within the utricle tissue that made contact with vestibular hair cells. A proportion of hNSC-derived cells showed spontaneous firing activities, similar to those observed in cultured mouse vestibular ganglion cells. However, hNSC-derived cells around the mouse utricle persisted as immature neurons or occasionally differentiated into putative astrocytes. Moreover, electrophysiological examination showed hNSC-derived cells around utricles did not exhibit any obvious spontaneous firing activities. CONCLUSIONS: Injected human neural stem cells (hNSCs) showed signs of morphological maturation including reconnection to denervated hair cells and partial physiological maturation, suggesting hNSC-derived cells possibly differentiated into neurons. PMID- 27196940 TI - Chronic myelogenous leukaemia exosomes modulate bone marrow microenvironment through activation of epidermal growth factor receptor. AB - Chronic myelogenous leukaemia (CML) is a clonal myeloproliferative disorder. Recent evidence indicates that altered crosstalk between CML and mesenchymal stromal cells may affect leukaemia survival; moreover, vesicles released by both tumour and non-tumour cells into the microenvironment provide a suitable niche for cancer cell growth and survival. We previously demonstrated that leukaemic and stromal cells establish an exosome-mediated bidirectional crosstalk leading to the production of IL8 in stromal cells, thus sustaining the survival of CML cells. Human cell lines used are LAMA84 (CML cells), HS5 (stromal cells) and bone marrow primary stromal cells; gene expression and protein analysis were performed by real-time PCR and Western blot. IL8 and MMP9 secretions were evaluated by ELISA. Exosomes were isolated from CML cells and blood samples of CML patients. Here, we show that LAMA84 and CML patients' exosomes contain amphiregulin (AREG), thus activating epidermal growth factor receptor (EGFR) signalling in stromal cells. EGFR signalling increases the expression of SNAIL and its targets, MMP9 and IL8. We also demonstrated that pre-treatment of HS5 with LAMA84 exosomes increases the expression of annexin A2 that promotes the adhesion of leukaemic cells to the stromal monolayer, finally supporting the growth and invasiveness of leukaemic cells. Leukaemic and stromal cells establish a bidirectional crosstalk: exosomes promote proliferation and survival of leukaemic cells, both in vitro and in vivo, by inducing IL8 secretion from stromal cells. We propose that this mechanism is activated by a ligand-receptor interaction between AREG, found in CML exosomes, and EGFR in bone marrow stromal cells. PMID- 27196943 TI - Identification of a novel HLA-C*03 variant, C*03:303, by sequence-based typing in a Dai Chinese individual. AB - HLA-C*03:303 has one nonsynonymous nucleotide change from HLA-C*03:04:01:01 in codon 194, exon 4 (GTC>GCC). PMID- 27196945 TI - Facile One-Step Strategy for Highly Boosted Microbial Extracellular Electron Transfer of the Genus Shewanella. AB - High performance of bacterial extracellular electron transfer (EET) is essentially important for its practical applications in versatile bioelectric fields. We developed a facile one-step approach to dramatically boost the bacterial EET activity 75-fold by exogenous addition of ethylenediamine tetraacetic acid disodium salt (EDTA-2Na, 1 mM) into the electrochemical cells, where the anodic process of microbial EET was monitored. We propose that EDTA-2Na enables both the alternation of the local environment around the c-type cytochromes located on the outer membrane channels (OMCs), which therefore changes the redox behavior of OMCs in mediating the EET process, and the formation of densely packed biofilm that can further facilitate the EET process. As a synergistic effect, the highly boosted bacterial EET activity was achieved. The method shows good generality for versatile bioelectrical bacteria. We envision that the method is also applicable for constructing various bioelectric devices. PMID- 27196947 TI - Synthesis of alpha-Amidoketones from Vinyl Esters via a Catalytic/Thermal Cascade Reaction. AB - A straightforward, modular, and atom-efficient method is reported for the synthesis of alpha-amidoketones from vinyl esters via a cascade reaction including hydroformylation, condensation with a primary amine, and a rearrangement step giving water as the only byproduct. The reaction sequence can be performed in one pot or as a three-step procedure. The synthetic applicability is demonstrated by the preparation of different alpha-amidoketones in moderate to good yields. PMID- 27196944 TI - Crystal Structure of Hypusine-Containing Translation Factor eIF5A Bound to a Rotated Eukaryotic Ribosome. AB - Eukaryotic translation initiation factor eIF5A promotes protein synthesis by resolving polyproline-induced ribosomal stalling. Here, we report a 3.25-A resolution crystal structure of eIF5A bound to the yeast 80S ribosome. The structure reveals a previously unseen conformation of an eIF5A-ribosome complex and highlights a possible functional link between conformational changes of the ribosome during protein synthesis and the eIF5A-ribosome association. PMID- 27196948 TI - Multidrug-resistant bacteria in hematology patients: emerging threats. AB - Multidrug-resistant (MDR) bacteria, particularly Gram negatives, such as Enterobacteriaceae resistant to third-generation cephalosporins or carbapenems and MDR Pseudomonas aeruginosa, are increasingly frequent in hematology patients. The prevalence of different resistant species varies significantly between centers. Thus, the knowledge of local epidemiology is mandatory for deciding the most appr-opriate management protocols. In the era of increasing antibiotic resistance, empirical therapy of febrile neutropenia should be individualized. A de-escalation approach is recommended in case of severe clinical presentation in patients who are at high risk for infection with a resistant strain. Targeted therapy of an MDR Gram negative usually calls for a combination treatment, although no large randomized trials exist in this setting. Infection control measures are the cornerstone of limiting the spread of MDR pathogens in hematology units. PMID- 27196946 TI - Movement Assessment of Children (MAC): validity, reliability, stability and sensitivity to change in typically developing children. AB - AIM: The purpose of this study was to establish the validity, reliability, stability and sensitivity to change of the family-centred Movement Assessment of Children (MAC) in typically developing infants/toddlers from 2 months (1 month 16 days) to 2 years (24 months 15 days) of age. BACKGROUND: Assessment of infant/toddler motor development is critical so that infants and toddlers who are at-risk for developmental delay or whose functional motor development is delayed can be monitored and receive therapy to improve their developmental outcomes. Infants/toddlers are thought to be more responsive during the MAC assessment because parents and siblings participate and elicit responses. METHODS: Two hundred seventy six children and 405 assessments contributed to the establishment of age-related parameters for typically developing infants and toddlers on the MAC. The MAC assesses three core domains of functional movement (head control, upper extremities and hands, pelvis and lower extremities), and generates a core total score. Four explanatory domains serve to alert examiners to factors that may impact atypical development (general observations, special senses, primitive reflexes/reactions, muscle tone). Construct validity of functional motor development was examined using the relationship between incremental increases in scores and increases in participants' ages. Subsamples were used to establish inter-rater reliability, test-retest reliability, stability and sensitivity to change. RESULTS: Construct validity was established and inter-rater reliability ICCs for the core items and core total ranged from 0.83 to 0.99. Percent agreement for the explanatory items ranged from 0.72 to 0.96. Stability within age grouping was consistent from baseline to 6 months post-baseline, and sensitivity to change from baseline to 6 months was significant for all core items and the total score. CONCLUSION: The MAC has proven to be a well constructed assessment of infant and toddler functional motor development. It is a family-centred and efficient tool that can be used to assess and follow-up of infants and toddlers from 2 months to 2 years. PMID- 27196949 TI - Efficacy and Safety of Radiofrequency Catheter Ablation of Tachyarrhythmias in 123 Children Under 3 Years of Age. AB - BACKGROUND: The risk-benefit ratio of radiofrequency catheter ablation (RFCA) in infants and toddlers remains controversial. Experience with RFCA in these patients is limited. This work is intended to describe the efficacy and safety of RFCA in children under 3 years of age with tachycardia complicated by drug resistance, drug intolerance, or tachycardia-induced cardiomyopathy. METHODS: We retrospectively reviewed data from 123 consecutive children under 3 years of age (mean, 2.3 +/- 0.8 years; weight, 13.6 +/- 2.8 kg) with tachycardia complicated by drug resistance, drug intolerance, or tachycardia-induced cardiomyopathy; the children underwent an electrophysiology study between 1994 and 2014 at our center. Fifteen children had congenital heart disease, and 27 children were under 1 year of age. Among the 109 children who underwent RFCA, acute success rate (no inducible arrhythmia before procedure completion), 2-year rate of symptomatic tachyarrhythmia recurrence, and complication rate were assessed. RESULTS: Among the 123 children studied, 76.4% had atrioventricular reentrant tachycardia, 5.7% had atrioventricular nodal reentrant tachycardia, 2.4% had focal atrial tachycardia, 6.5% had atrial flutter, and 4.1% had idiopathic left ventricular tachycardia. For RFCA, the acute success rate was 94.5%, and the 2-year recurrence rate was 6.8%, without any major complications. CONCLUSION: RFCA appears to be an effective and safe therapeutic option in selected small children with tachycardia resistant to conventional medical management, tachycardia complicated by drug intolerance, or tachycardia-induced cardiomyopathy. PMID- 27196950 TI - Endometriosis, Ovarian Reserve and Live Birth Rate Following In Vitro Fertilization/Intracytoplasmic Sperm Injection. AB - Purpose To evaluate whether women with endometriosis have different ovarian reserves and reproductive outcomes when compared with women without this diagnosis undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI), and to compare the reproductive outcomes between women with and without the diagnosis considering the ovarian reserve assessed by antral follicle count (AFC). Methods This retrospective cohort study evaluated all women who underwent IVF/ICSI in a university hospital in Brazil between January 2011 and December 2012. All patients were followed up until a negative pregnancy test or until the end of the pregnancy. The primary outcomes assessed were number of retrieved oocytes and live birth. Women were divided into two groups according to the diagnosis of endometriosis, and each group was divided again into a group that had AFC <= 6 (poor ovarian reserve) and another that had AFC >= 7 (normal ovarian reserve). Continuous variables with normal distribution were compared using unpaired t-test, and those without normal distribution, using Mann-Whitney test. Binary data were compared using either Fisher's exact test or Chi-square (chi(2)) test. The significance level was set as p < 0.05. Results 787 women underwent IVF/ICSI (241 of which had endometriosis). Although the mean age has been similar between women with and without the diagnosis of endometriosis (33.8 +/- 4 versus 33.7 +/- 4.4 years, respectively), poor ovarian reserves were much more common in women with endometriosis (39.8 versus 22.7%). The chance of achieving live birth was similar between women with the diagnosis of endometriosis and those without it (19.1 versus 22.5%), and also when considering only women with a poor ovarian reserve (9.4 versus 8.9%) and only those with a normal ovarian reserve (25.5 versus 26.5%). Conclusions Women diagnosed with endometriosis are more likely to have a poor ovarian reserve; however, their chance of conceiving by IVF/ICSI is similar to the one observed in patients without endometriosis and with a comparable ovarian reserve. PMID- 27196951 TI - Correlation of Menopausal Symptoms and Quality of Life with Physical Performance in Middle-Aged Women. AB - Introduction Some studies have investigated the influence of hormonal deficits and menopausal status in muscle disorders of women. However, it has not been investigated the relationship of both climacteric symptoms and the perception of quality of life with physical performance. Objective To evaluate the correlation of menopausal symptoms and quality of life with physical performance in middle aged women. Methods This cross-sectional study was performed from April to November 2013 in the municipality of Parnamirim, in the Brazilian state, Rio Grande do Norte. The sample was composed of 497 women aged 40-65 years. The Menopause Rating Scale (MRS) and the Utian Quality of Life (UQOL) questionnaire were used to evaluate menopausal symptoms and quality of life respectively. Measures of physical performance included handgrip strength, knee extensor and flexor strengths (using an isometric dynamometer), gait speed, and chair stand test. The correlation between menopausal symptoms and quality of life with physical performance was assessed by Pearson's correlation coefficient with significance set at p < 0.05 and a confidence interval of 95%. Results There was a significant negative correlation between handgrip strength and somatic MRS score (p = 0.002) and total MRS score (p = 0.03). There was a significant correlation between knee flexor strength and sit-to-stand time and all menopausal symptom areas (p < 0.05), except psychological symptoms. There was a positive correlation between physical performance of the knee flexors and quality of life items including occupational (p = 0.001), emotional (p = 0.005), and total UQOL (p = 0.01), but a negative correlation with sit-to-stand time and all quality of life domains (p < 0.05). Conclusion A greater intensity of menopausal symptoms and worse quality of life were related with worse physical performance. Thus, preventive measures should be implemented to avoid adverse effects on physical performance at more advanced ages. PMID- 27196952 TI - Prevalence and Causes of Visual Impairment and Blindness in Chinese American Adults: The Chinese American Eye Study. AB - IMPORTANCE: Visual impairment (VI) and blindness continue to be major public health problems worldwide. Despite previously published studies on VI in Chinese and other racial/ethnic populations, there are no data specific to Chinese American adults. OBJECTIVES: To determine the age- and sex-specific prevalence and causes of VI and blindness in adult Chinese Americans and to compare the prevalence to other racial/ethnic groups. DESIGN, SETTING, AND PARTICIPANTS: In this population-based, cross-sectional study of 10 US Census tracts in the city of Monterey Park, California, 4582 Chinese American adults 50 years and older underwent complete ophthalmologic examinations, including measurement of presenting and best-corrected visual acuity (BCVA) for distance using the Early Treatment Diabetic Retinopathy Study protocol from February 1, 2010, through October 31, 2013. MAIN OUTCOMES AND MEASURES: Age-specific prevalence and causes of VI and blindness for presenting and BCVA. RESULTS: Of the 5782 eligible adults, 4582 (79.2%) completed an in-clinic eye examination. Of the 4582 participants, most were born in China (3149 [68.7%]), female (2901 [63.3%]), and married (3458 [75.5%]). The mean (SD) age was 61 (9) years. The prevalence of presenting VI was 3.0% (95% CI, 2.5%-3.5%), with 60.0% of this prevalence being attributed to uncorrected refractive error. The overall age-adjusted prevalence for VI (BCVA of <=20/40 in the better eye) was 1.2% (95% CI, 0.9%-1.5%). The overall age-adjusted prevalence of blindness (BCVA of <=20/200 in the better seeing eye) was 0.07% (95% CI, 0%-0.2%). The prevalence of VI and blindness was higher in older Chinese Americans compared with younger. The primary causes of VI were cataracts and myopic retinopathy; the primary cause of blindness was myopic retinopathy. CONCLUSIONS AND RELEVANCE: The prevalence of VI in Chinese Americans is similar to that of non-Hispanic white and Latino individuals in the United States and similar to or lower than the prevalence previously reported for Chinese adults from non-US studies. The prevalence of blindness is lower than that noted in other US or non-US studies. Myopic retinopathy is a frequent cause of VI and blindness in Chinese Americans that has not been commonly observed in other racial/ethnic groups. Because myopia frequently develops at a young age, Chinese Americans should be educated regarding the importance of regular screening of preschool and school-aged children to reduce the development and progression of myopia. PMID- 27196953 TI - The iron homeostasis network and hepatitis C virus - a new challenge in the era of directly acting antivirals. PMID- 27196954 TI - Determinant Factors of Long-Term Performance Development in Young Swimmers. AB - PURPOSE: To develop a performance predictor model based on swimmers' biomechanical profile, relate the partial contribution of the main predictors with the training program, and analyze the time effect, sex effect, and time * sex interaction. METHODS: 91 swimmers (44 boys, 12.04 +/- 0.81 y; 47 girls, 11.22 +/- 0.98 y) evaluated during a 3-y period. The decimal age and anthropometric, kinematic, and efficiency features were collected 10 different times over 3 seasons (ie, longitudinal research). Hierarchical linear modeling was the procedure used to estimate the performance predictors. RESULTS: Performance improved between season 1 early and season 3 late for both sexes (boys 26.9% [20.88;32.96], girls 16.1% [10.34;22.54]). Decimal age (estimate [EST] -2.05, P < .001), arm span (EST -0.59, P < .001), stroke length (EST 3.82; P = .002), and propelling efficiency (EST -0.17, P = .001) were entered in the final model. CONCLUSION: Over 3 consecutive seasons young swimmers' performance improved. Performance is a multifactorial phenomenon where anthropometrics, kinematics, and efficiency were the main determinants. The change of these factors over time was coupled with the training plans of this talent identification and development program. PMID- 27196955 TI - Computed tomography of the brain following out of hospital cardiac arrest: Neuro prognostication or phrenology? PMID- 27196956 TI - Off-Pump Coronary Artery Bypass Grafting and Transaortic Transcatheter Aortic Valve Replacement. AB - We sought to demonstrate the effectiveness of off-pump coronary artery bypass grafting and transcatheter aortic valve replacement in two patients with porcelain aortas and lesions that could not be optimally treated with percutaneous coronary intervention. Patients with aortic stenosis and coronary artery disease who are too high-risk for conventional surgical aortic valve replacement and coronary artery bypass grafting due to comorbidities and porcelain aorta, and who do not have the appropriate anatomy for percutaneous coronary intervention should be considered for concomitant transcatheter aortic valve replacement and off-pump coronary artery bypass grafting. doi: 10.1111/jocs.12762 (J Card Surg 2016;31:435-438). PMID- 27196957 TI - Tsunami waves extensively resurfaced the shorelines of an early Martian ocean. AB - It has been proposed that ~3.4 billion years ago an ocean fed by enormous catastrophic floods covered most of the Martian northern lowlands. However, a persistent problem with this hypothesis is the lack of definitive paleoshoreline features. Here, based on geomorphic and thermal image mapping in the circum Chryse and northwestern Arabia Terra regions of the northern plains, in combination with numerical analyses, we show evidence for two enormous tsunami events possibly triggered by bolide impacts, resulting in craters ~30 km in diameter and occurring perhaps a few million years apart. The tsunamis produced widespread littoral landforms, including run-up water-ice-rich and bouldery lobes, which extended tens to hundreds of kilometers over gently sloping plains and boundary cratered highlands, as well as backwash channels where wave retreat occurred on highland-boundary surfaces. The ice-rich lobes formed in association with the younger tsunami, showing that their emplacement took place following a transition into a colder global climatic regime that occurred after the older tsunami event. We conclude that, on early Mars, tsunamis played a major role in generating and resurfacing coastal terrains. PMID- 27196958 TI - Romantic Relationships and Relationship Satisfaction Among Adults With Asperger Syndrome and High-Functioning Autism. AB - OBJECTIVE: Individuals with autism spectrum disorder (ASD) often experience difficulties in maintaining romantic relationships. In this study high functioning adults with ASD were examined concerning their romantic relationship interest and experience. METHOD: Participants, 31 recruited via an outpatient clinic and 198 via an online survey, were asked to answer a number of self-report questionnaires. The total sample comprised 229 high-functioning adults with ASD (40% males, average age: 35 years). RESULTS: Of the total sample, 73% indicated romantic relationship experience and only 7% had no desire to be in a romantic relationship. ASD individuals whose partner was also on the autism spectrum were significantly more satisfied with their relationship than those with neurotypical partners. Severity of autism, schizoid symptoms, empathy skills, and need for social support were not correlated with relationship status. CONCLUSION: Our findings indicate that the vast majority of high-functioning adults with ASD are interested in romantic relationships. PMID- 27196959 TI - The perceived impact of interprofessional information sharing on young people about their sexual healthcare. AB - This article presents the results from an analysis of data from service providers and young adults who were formerly in state care about how information about the sexual health of young people in state care is managed. In particular, the analysis focuses on the perceived impact of information sharing between professionals on young people. Twenty-two service providers from a range of professions including social work, nursing and psychology, and 19 young people aged 18-22 years who were formerly in state care participated in the study. A qualitative approach was employed in which participants were interviewed in depth and data were analysed using modified analytical induction (Bogdan & Biklen, 2007). Findings suggest that within the care system in which service provider participants worked it was standard practice that sensitive information about a young person's sexual health would be shared across team members, even where there appeared to be no child protection issues. However, the accounts of the young people indicated that they experienced the sharing of information in this way as an invasion of their privacy. An unintended outcome of a high level of information sharing within teams is that the privacy of the young person in care is compromised in a way that is not likely to arise in the case of young people who are not in care. This may deter young people from availing themselves of the sexual health services. PMID- 27196960 TI - Fully Automated Islet Cell Counter (ICC) for the Assessment of Islet Mass, Purity, and Size Distribution by Digital Image Analysis. AB - For isolated pancreatic islet cell preparations, it is important to be able to reliably assess their mass and quality, and for clinical applications, it is part of the regulatory requirement. Accurate assessment, however, is difficult because islets are spheroid-like cell aggregates of different sizes (<50 to 500 MUm) resulting in possible thousandfold differences between the mass contribution of individual particles. The current standard manual counting method that uses size based group classification is known to be error prone and operator dependent. Digital image analysis (DIA)-based methods can provide less subjective, more reproducible, and better-documented islet cell mass (IEQ) estimates; however, so far, none has become widely accepted or used. Here we present results obtained using a compact, self-contained islet cell counter (ICC3) that includes both the hardware and software needed for automated islet counting and requires minimal operator training and input; hence, it can be easily adapted at any center and could provide a convenient standardized cGMP-compliant IEQ assessment. Using cross-validated sample counting, we found that for most human islet cell preparations, ICC3 provides islet mass (IEQ) estimates that correlate well with those obtained by trained operators using the current manual SOP method ( r2 = 0.78, slope = 1.02). Variability and reproducibility are also improved compared to the manual method, and most of the remaining variability (CV = 8.9%) results from the rearrangement of the islet particles due to movement of the sample between counts. Characterization of the size distribution is also important, and the present digitally collected data allow more detailed analysis and coverage of a wider size range. We found again that for human islet cell preparations, a Weibull distribution function provides good description of the particle size. PMID- 27196961 TI - Treatment of EGFR-Mutant Lung Cancers After Progression in Patients Receiving First-Line EGFR Tyrosine Kinase Inhibitors : A Review. AB - IMPORTANCE: Patients with EGFR-mutant lung cancer benefit from treatment with EGFR inhibitors such as erlotinib, gefitinib, and afatinib, but outcomes are limited by the eventual development of resistance to these agents. Over half of patients acquire a secondary T790M mutation in EGFR at the time of progression and a substantial minority develops resistance through other mechanisms. Multiple treatment strategies are now available to patients whose disease has progressed on their initial EGFR inhibitor, including therapies targeting both T790M, and non-T790M-mediated resistance. OBSERVATIONS: This review summarizes information about and current treatment strategies for patients with EGFR-mutant lung cancer whose disease progresses on their initial EGFR inhibitor, including those with T790M and other types of acquired resistance. Postprogression therapy should be tailored based on identified resistance mechanisms, sites, and pace of disease progression, and patient preference. Biopsy and genotyping of resistant tissue or plasma are essential to identifying resistance mechanisms and selecting the most appropriate treatment when patients' disease progresses during treatment with an initial EGFR inhibitor. Third-generation EGFR inhibitors are generally preferred for patients with T790M-positive resistance, whereas standard chemotherapy and clinical trials are preferred for those without T790M. For select patients, treatment can be continued beyond progression and local ablative therapies can be used to target sites of oligoprogression. CONCLUSIONS AND RELEVANCE: Treatment for patients who progress on their initial EGFR inhibitor should be tailored to identified resistance mechanisms and sites of progression. Emerging reports about resistance to third-generation EGFR inhibitors will lay the groundwork for overcoming the next generation of resistance, and further research is needed to develop more effective therapies. PMID- 27196963 TI - Vapor Pressure of Aqueous Solutions of Electrolytes Reproduced with Coarse Grained Models without Electrostatics. AB - The vapor pressure of water is a key property in a large class of applications from the design of membranes for fuel cells and separations to the prediction of the mixing state of atmospheric aerosols. Molecular simulations have been used to compute vapor pressures, and a few studies on liquid mixtures and solutions have been reported on the basis of the Gibbs Ensemble Monte Carlo method in combination with atomistic force fields. These simulations are costly, making them impractical for the prediction of the vapor pressure of complex materials. The goal of the present work is twofold: (1) to demonstrate the use of the grand canonical screening approach ( Factorovich , M. H. J. Chem. Phys. 2014 , 140 , 064111 ) to compute the vapor pressure of solutions and to extend the methodology for the treatment of systems without a liquid-vapor interface and (2) to investigate the ability of computationally efficient high-resolution coarse grained models based on the mW monatomic water potential and ions described exclusively with short-range interactions to reproduce the relative vapor pressure of aqueous solutions. We find that coarse-grained models of LiCl and NaCl solutions faithfully reproduce the experimental relative pressures up to high salt concentrations, despite the inability of these models to predict cohesive energies of the solutions or the salts. A thermodynamic analysis reveals that the coarse-grained models achieve the experimental activity coefficients of water in solution through a compensation of severely underestimated hydration and vaporization free energies of the salts. Our results suggest that coarse-grained models developed to replicate the hydration structure and the effective ion-ion attraction in solution may lead to this compensation. Moreover, they suggest an avenue for the design of coarse-grained models that accurately reproduce the activity coefficients of solutions. PMID- 27196962 TI - Phytoremediation of groundwater contaminated with pesticides using short-rotation willow crops: A case study of an apple orchard. AB - The occurrence of pesticides in groundwater represents an important health issue, notably for population whose drinking water supply source is located in agricultural areas. However, few solutions have been considered with regard to this issue. We tested the efficacy of a vegetal filtering system made of shrub willows planted at a high density (16,000 plants ha(-1)) to filter or degrade pesticides found in the groundwater flowing out of an apple orchard. Ethylene urea (EU), ethylene thiourea (ETU), tetrahydrophthalimide (THPI), atrazine, and desethylatrazine were monitored in the soil solution in willow and control plots over one growing season. ETU and atrazine concentrations were lower in the willow plots relative to the control plots, whereas desethylatrazine concentration was higher in the willow plots. No significant difference was detected for EU and THPI. Furthermore, pesticide concentrations displayed complex temporal patterns. These results suggest that willow filter systems can filter or degrade pesticides, notably ETU and atrazine, and could be used for phytoremediation purposes. Yet, this potential remains to be quantified with further studies using experimental settings allowing more estimation in time and space. PMID- 27196965 TI - Accepted Abstracts from the International Brain Injury Association's Eleventh World Congress on Brain Injury March 2-5, 2016 The Hague World Forum The Netherlands. PMID- 27196964 TI - Topical delivery of a Rho-kinase inhibitor to the cornea via mucoadhesive film. AB - The application of inhibitors of the Rho kinase pathway (ROCK inhibitors) to the surface of the eye in the form of eyedrops has beneficial effects which aid the recovery of diseased or injured endothelial cells that line the inner surface of the cornea. The aim of this study was to test the plausibility of delivering a selective ROCK inhibitor, Y-27632, to the cornea using a thin polymeric film. Mucoadhesive polymeric thin films were prepared incorporating Y-27632 and diffusional release into PBS was determined. Topical ocular delivery from the applied film was investigated using freshly excised porcine eyes and eyedrops of equivalent concentration acted as comparators; after 24h the formulations were removed and the corneas extracted. Drug-loaded thin polymeric films, with high clarity and pliability were produced. ROCK inhibitor Y-27632 was weakly retained within the film, with release attaining equilibrium after 1h. This in turn facilitated its rapid ocular delivery, and an approximately three-fold greater penetration of Y-27632 into cryoprobe-treated corneas was observed from the thin film (p<0.01) compared to eyedrops. These findings support the further development of ROCK inhibitor delivery to the cornea via release from thin mucoadhesive films to treat vision loss cause by corneal endothelial dysfunction. PMID- 27196966 TI - Integration of multiple biological features yields high confidence human protein interactome. AB - The biological function of a protein is usually determined by its physical interaction with other proteins. Protein-protein interactions (PPIs) are identified through various experimental methods and are stored in curated databases. The noisiness of the existing PPI data is evident, and it is essential that a more reliable data is generated. Furthermore, the selection of a set of PPIs at different confidence levels might be necessary for many studies. Although different methodologies were introduced to evaluate the confidence scores for binary interactions, a highly reliable, almost complete PPI network of Homo sapiens is not proposed yet. The quality and coverage of human protein interactome need to be improved to be used in various disciplines, especially in biomedicine. In the present work, we propose an unsupervised statistical approach to assign confidence scores to PPIs of H. sapiens. To achieve this goal PPI data from six different databases were collected and a total of 295,288 non-redundant interactions between 15,950 proteins were acquired. The present scoring system included the context information that was assigned to PPIs derived from eight biological attributes. A high confidence network, which included 147,923 binary interactions between 13,213 proteins, had scores greater than the cutoff value of 0.80, for which sensitivity, specificity, and coverage were 94.5%, 80.9%, and 82.8%, respectively. We compared the present scoring method with others for evaluation. Reducing the noise inherent in experimental PPIs via our scoring scheme increased the accuracy significantly. As it was demonstrated through the assessment of process and cancer subnetworks, this study allows researchers to construct and analyze context-specific networks via valid PPI sets and one can easily achieve subnetworks around proteins of interest at a specified confidence level. PMID- 27196967 TI - Simulating the multicellular homeostasis with a cell-based discrete receptor dynamics model: The non-mutational origin of cancer and aging. AB - The purpose of the study is to investigate the multicellular homeostasis in epithelial tissues over very large timescales. Inspired by the receptor dynamics of IBCell model proposed by Rejniak et al. an on-grid agent-based model for multicellular system is constructed. Instead of observing the multicellular architectural morphologies, the diversity of homeostatic states is quantitatively analyzed through a substantial number of simulations by measuring three new order parameters, the phenotypic population structure, the average proliferation age and the relaxation time to stable homeostasis. Nearby the interfaces of distinct homeostatic phases in 3D phase diagrams of the three order parameters, intermediate quasi-stable phases of slow dynamics that features quasi-stability with a large spectrum of relaxation timescales are found. A further exploration on the static and dynamic correlations among the three order parameters reveals that the quasi-stable phases evolve towards two terminations, tumorigenesis and degeneration, which are respectively accompanied by rejuvenation and aging. With the exclusion of the environmental impact and the mutational strategies, the results imply that cancer and aging may share the non-mutational origin in the intrinsic slow dynamics of the multicellular systems. PMID- 27196968 TI - Synaptic Menage a Trois. AB - Regulation of neurotransmitter receptor localization is critical for synaptic function and plasticity. In this issue of Neuron, Matsuda and colleagues (Matsuda et al., 2016) uncover a transsynaptic complex consisting of neurexin-3, C1q-like proteins, and kainate receptors that drives glutamate receptor clustering at hippocampal synapses. PMID- 27196969 TI - Quantum Disentanglement: Electrical Analysis of the Complex Roles of Ions in Filling Vesicles with Glutamate. AB - By expressing vesicular glutamate transporters at high levels in plasma membrane and applying voltage clamp methods, Eriksen et al. (2016) have identified a Cl(-) channel in the transporter that is coactivated by protons and Cl(-). PMID- 27196970 TI - A Central Move for CB2 Receptors. AB - The function of the CB2 cannabinoid receptor in the brain has long been a matter of debate. In this issue of Neuron, Stempel et al. (2016) describe a mechanism whereby endocannabinoid production leads to a cell-intrinsic hyperpolarization that controls self activity. PMID- 27196971 TI - Continuous Time Representations of Song in Zebra Finches. AB - Neurons in the songbird nucleus HVC produce premotor bursts time locked to song with millisecond precision. In this issue of Neuron, Lynch et al. (2016) and Picardo et al. (2016) provide convincing evidence that the population of these bursts contain a continuous representation of time throughout song. PMID- 27196972 TI - Understanding Dopaminergic Cell Death Pathways in Parkinson Disease. AB - Parkinson disease (PD) is a multifactorial neurodegenerative disorder, the etiology of which remains largely unknown. Progressive impairment of voluntary motor control, which represents the primary clinical feature of the disease, is caused by a loss of midbrain substantia nigra dopamine (DA) neurons. We present here a synthetic overview of cell-autonomous mechanisms that are likely to participate in DA cell death in both sporadic and inherited forms of the disease. In particular, we describe how damage to vulnerable DA neurons may arise from cellular disturbances produced by protein misfolding and aggregation, disruption of autophagic catabolism, endoplasmic reticulum (ER) stress, mitochondrial dysfunction, or loss of calcium homeostasis. Where pertinent, we show how these mechanisms may mutually cooperate to promote neuronal death. PMID- 27196973 TI - The Anterior Cingulate Gyrus and Social Cognition: Tracking the Motivation of Others. AB - The anterior cingulate cortex (ACC) is implicated in a broad range of behaviors and cognitive processes, but it has been unclear what contribution, if any, the ACC makes to social behavior. We argue that anatomical and functional evidence suggests that a specific sub-region of ACC-in the gyrus (ACCg)-plays a crucial role in processing social information. We propose that the computational properties of the ACCg support a contribution to social cognition by estimating how motivated other individuals are and dynamically updating those estimates when further evidence suggests they have been erroneous. Notably this model, based on vicarious motivation and error processing, provides a unified account of neurophysiological and neuroimaging evidence that the ACCg is sensitive to costs, benefits, and errors during social interactions. Furthermore, it makes specific, testable predictions about a key mechanism that may underpin variability in socio cognitive abilities in health and disease. PMID- 27196974 TI - TREM2 Haplodeficiency in Mice and Humans Impairs the Microglia Barrier Function Leading to Decreased Amyloid Compaction and Severe Axonal Dystrophy. AB - Haplodeficiency of the microglia gene TREM2 increases risk for late-onset Alzheimer's disease (AD) but the mechanisms remain uncertain. To investigate this, we used high-resolution confocal and super-resolution (STORM) microscopy in AD-like mice and human AD tissue. We found that microglia processes, rich in TREM2, tightly surround early amyloid fibrils and plaques promoting their compaction and insulation. In Trem2- or DAP12-haplodeficient mice and in humans with R47H TREM2 mutations, microglia had a markedly reduced ability to envelop amyloid deposits. This led to an increase in less compact plaques with longer and branched amyloid fibrils resulting in greater surface exposure to adjacent neurites. This was associated with more severe neuritic tau hyperphosphorylation and axonal dystrophy around amyloid deposits. Thus, TREM2 deficiency may disrupt the formation of a neuroprotective microglia barrier that regulates amyloid compaction and insulation. Pharmacological modulation of this barrier could be a novel therapeutic strategy for AD. PMID- 27196975 TI - Enhanced GABA Transmission Drives Bradykinesia Following Loss of Dopamine D2 Receptor Signaling. AB - Bradykinesia is a prominent phenotype of Parkinson's disease, depression, and other neurological conditions. Disruption of dopamine (DA) transmission plays an important role, but progress in understanding the exact mechanisms driving slowness of movement has been impeded due to the heterogeneity of DA receptor distribution on multiple cell types within the striatum. Here we show that selective deletion of DA D2 receptors (D2Rs) from indirect-pathway medium spiny neurons (iMSNs) is sufficient to impair locomotor activity, phenocopying DA depletion models of Parkinson's disease, despite this mouse model having intact DA transmission. There was a robust enhancement of GABAergic transmission and a reduction of in vivo firing in striatal and pallidal neurons. Mimicking D2R signaling in iMSNs with Gi-DREADDs restored the level of tonic GABAergic transmission and rescued the motor deficit. These findings indicate that DA, through D2R activation in iMSNs, regulates motor output by constraining the strength of GABAergic transmission. PMID- 27196977 TI - Rhythmic Continuous-Time Coding in the Songbird Analog of Vocal Motor Cortex. AB - Songbirds learn and produce complex sequences of vocal gestures. Adult birdsong requires premotor nucleus HVC, in which projection neurons (PNs) burst sparsely at stereotyped times in the song. It has been hypothesized that PN bursts, as a population, form a continuous sequence, while a different model of HVC function proposes that both HVC PN and interneuron activity is tightly organized around motor gestures. Using a large dataset of PNs and interneurons recorded in singing birds, we test several predictions of these models. We find that PN bursts in adult birds are continuously and nearly uniformly distributed throughout song. However, we also find that PN and interneuron firing rates exhibit significant 10 Hz rhythmicity locked to song syllables, peaking prior to syllable onsets and suppressed prior to offsets-a pattern that predominates PN and interneuron activity in HVC during early stages of vocal learning. PMID- 27196976 TI - Population-Level Representation of a Temporal Sequence Underlying Song Production in the Zebra Finch. AB - The zebra finch brain features a set of clearly defined and hierarchically arranged motor nuclei that are selectively responsible for producing singing behavior. One of these regions, a critical forebrain structure called HVC, contains premotor neurons that are active at precise time points during song production. However, the neural representation of this behavior at a population level remains elusive. We used two-photon microscopy to monitor ensemble activity during singing, integrating across multiple trials by adopting a Bayesian inference approach to more precisely estimate burst timing. Additionally, we examined spiking and motor-related synaptic inputs using intracellular recordings during singing. With both experimental approaches, we find that premotor events do not occur preferentially at the onsets or offsets of song syllables or at specific subsyllabic motor landmarks. These results strongly support the notion that HVC projection neurons collectively exhibit a temporal sequence during singing that is uncoupled from ongoing movements. PMID- 27196979 TI - Bud break responds more strongly to daytime than night-time temperature under asymmetric experimental warming. AB - Global warming is diurnally asymmetric, leading to a less cold, rather than warmer, climate. We investigated the effects of asymmetric experimental warming on plant phenology by testing the hypothesis that daytime warming is more effective in advancing bud break than night-time warming. Bud break was monitored daily in Picea mariana seedlings belonging to 20 provenances from Eastern Canada and subjected to daytime and night-time warming in growth chambers at temperatures varying between 8 and 16 degrees C. The higher advancements of bud break and shorter times required to complete the phenological phases occurred with daytime warming. Seedlings responded to night-time warming, but still with less advancement of bud break than under daytime warming. No advancement was observed when night-time warming was associated with a daytime cooling. The effect of the treatments was uniform across provenances. Our observations realized under controlled conditions allowed to experimentally demonstrate that bud break can advance under night-time warming, but to a lesser extent than under daytime warming. Prediction models using daily timescales could neglect the diverging influence of asymmetric warming and should be recalibrated for higher temporal resolutions. PMID- 27196978 TI - Neural Mechanisms of Hierarchical Planning in a Virtual Subway Network. AB - Planning allows actions to be structured in pursuit of a future goal. However, in natural environments, planning over multiple possible future states incurs prohibitive computational costs. To represent plans efficiently, states can be clustered hierarchically into "contexts". For example, representing a journey through a subway network as a succession of individual states (stations) is more costly than encoding a sequence of contexts (lines) and context switches (line changes). Here, using functional brain imaging, we asked humans to perform a planning task in a virtual subway network. Behavioral analyses revealed that humans executed a hierarchically organized plan. Brain activity in the dorsomedial prefrontal cortex and premotor cortex scaled with the cost of hierarchical plan representation and unique neural signals in these regions signaled contexts and context switches. These results suggest that humans represent hierarchical plans using a network of caudal prefrontal structures. VIDEO ABSTRACT. PMID- 27196980 TI - Fractional electron number, temperature, and perturbations in chemical reactions. AB - We provide a perspective on the role of non-integer electron number in the density functional theory approach to chemical reactivity (conceptual DFT), emphasizing that it is important to not only treat reagents as open systems, but also as non-isolated systems, in contact with their surroundings. The special case of well-separated reagents is treated in some detail, as is the case where reagents interact strongly. The resulting expressions for the chemical potential of an acid, MUacid = -(alphaI + A)/(1 + alpha), and a base, MUbase = -(I + alphaA)/(1 + alpha), elucidate and generalize the assumptions inherent in the chemical potential models of Mulliken (alpha = 1) and Gazquez, Cedillo, and Vela (alpha = 3). In the strongly-interacting limit, it is appropriate to model the effects of the environment as a state-specific effective temperature, thereby providing a rigorous justification for the phenomenological effective-temperature model one of the authors previously proposed. The framework for the strongly interacting limit subsumes our model for weakly-interacting subsystems at nonzero temperature, the case of open but otherwise noninteracting subsystems, and the zero-temperature limit. PMID- 27196981 TI - There is an "app" for that: Designing mobile phone technology to improve asthma action plan use in adolescent patients. AB - PURPOSE: Asthma burden affects mortality, morbidity, quality of life, and the economy. Written asthma action plans are standard of care according to national guidelines, but these plans are often not prescribed. The purpose of this project was to develop an asthma action plan application for smartphones. DATA SOURCES: A development studio was consulted for support in developing a smartphone application to code the software for the asthma action plan and assist in the design process. During development of the application, a survey was conducted to assist in design of the application and functionality. CONCLUSIONS: All survey participants agreed that the application was easy to use, could be used without written instruction, and was designed for adolescents with asthma of any severity. Patients and providers mostly agreed that the app would help provide information about what to do in the event of an asthma exacerbation, and the application would be used frequently. IMPLICATIONS FOR PRACTICE: There was consensus from both patients and providers that this application is not only functional but also helpful in the event of an asthma exacerbation. The project met the goal of designing a mobile phone application that would improve patient access to asthma action plans. PMID- 27196982 TI - Francisella Infection in Cultured Tilapia in Thailand and the Inflammatory Cytokine Response. AB - Francisella infections developed in freshwater Nile Tilapia Oreochromis niloticus and red tilapia Oreochromis spp. farms in Thailand during 2012-2014. The diseased fish were lethargic and pale in color and showed numerous white nodules in their enlarged spleens. Histopathological examination and electron microscopy suggested that the white nodules were multifocal granulomas consisting of coccobacilli within vacuolated cells. Isolation of Francisella-like bacteria was achieved from 42 of 100 samples, while polymerase chain reaction confirmed Francisella infections in all samples. Analysis of the 16S rRNA gene from samples obtained from three different geographical culture areas revealed more than 99% similarity with F. noatunensis subsp. orientalis. The influence of Francisella infection on inflammatory cytokines was determined on splenic cells of fish intraperitoneally injected with the bacteria (0.8 * 10(5) colony-forming units per fish). Infected tilapia showed significantly greater expression of the pro-inflammatory genes interleukin-1beta (IL-1beta) and tumor necrotic factor-alpha (TNF-alpha) within 24 h postinjection (hpi) and for up to 96 hpi. However, down-regulation of an anti-inflammatory gene, transforming growth factor-beta (TGF-beta) was observed as early as 24 hpi. This investigation demonstrates that an imbalance between pro and anti-inflammatory cytokines in response to the infection may account for the substantial number of granulomas in fish hematopoietic tissues that was found in the later stage of the disease. Received September 9, 2015; accepted December 13, 2015. PMID- 27196983 TI - Multiplex component-based allergen microarray in recent clinical studies. AB - During the last decades component-resolved diagnostics either as singleplex or multiplex measurements has been introduced into the field of clinical allergology, providing important information that cannot be obtained from extract based tests. Here we review recent studies that demonstrate clinical applications of the multiplex microarray technique in the diagnosis and risk assessment of allergic patients, and its usefulness in studies of allergic diseases. The usefulness of ImmunoCAP ISAC has been validated in a wide spectrum of allergic diseases like asthma, allergic rhinoconjunctivitis, atopic dermatitis, eosinophilic esophagitis, food allergy and anaphylaxis. ISAC provides a broad picture of a patient's sensitization profile from a single test, and provides information on specific and cross-reactive sensitizations that facilitate diagnosis, risk assessment, and disease management. Furthermore, it can reveal unexpected sensitizations which may explain anaphylaxis previously categorized as idiopathic and also display for the moment clinically non-relevant sensitizations. ISAC can facilitate a better selection of relevant allergens for immunotherapy compared with extract testing. Microarray technique can visualize the allergic march and molecular spreading in the preclinical stages of allergic diseases, and may indicate that the likelihood of developing symptomatic allergy is associated with specific profiles of sensitization to allergen components. ISAC is shown to be a useful tool in routine allergy diagnostics due to its ability to improve risk assessment, to better select relevant allergens for immunotherapy as well as detecting unknown sensitization. Multiplex component testing is especially suitable for patients with complex symptomatology. PMID- 27196984 TI - Prevalence and Predictors of Prehospital Pain Assessment and Analgesic Use in Military Trauma Patients, 2010-2013. AB - INTRODUCTION: Pain is the most common symptom in patients presenting for prehospital (PH) care. Research in civilian emergency medical systems has shown wide variability in PH pain assessment and analgesic practices, yet a minimal amount is known about pain assessment and analgesic intervention practices in the military, particularly when PH care is delivered in a combat zone. OBJECTIVE: To describe prehospital (PH) pain care practices for U.S. military personnel injured in Iraq and Afghanistan 2010-2013 and explore potential relationships to explain variation. METHODS: An exploratory retrospective, cross-sectional study of Department of Defense Trauma Registry data from 2010 to 2013 was performed. Demographic, clinical, or health system variables for associations with three outcomes: 1) pain assessment documentation; 2) pain severity (0-10 scale); and 3) analgesic administration (yes/no). Including only variables with significant associations, backward stepwise regression was used to develop explanatory models for each outcome. RESULTS: Patient records (n = 3,317) were evaluated for documentation of PH pain assessment and analgesic administration. The prevalence of PH pain score documentation was 37.8% (n = 1,253). Overall, the proportion of records with PH pain scores increased over time: 19.8% (2010), 35.1% (2011), 58.2% (2012), and 62.2% (2013). Severity of pain scores ranged 0-10; mean = 5.5 (SD = 3.1); median = 6 (IQR = 3-8). Analgesics were reported for 50.8% (n = 1,684), of whom 38.3% had a pain severity score documented. The pain assessment documentation model included any documented vital signs, injury year, and mechanism of injury and explained 19.3% of the variance in documentation. The pain severity model included vital signs and injury severity score (ISS) and explained 5.0% of the variance in severity. The analgesic model included any vital signs, pain severity, trauma type, mechanism of injury, ISS, and year. CONCLUSIONS: Pain assessment and treatment documentation improved each year, but remain suboptimal. Available data yielded poor prediction of the outcomes of interest, emphasizing the importance of individual assessment. Analgesic effectiveness could not be evaluated. PMID- 27196985 TI - Capillary electrophoresis as a method to determine underivatized urinary lipoarabinomannans, a biomarker of active tuberculosis caused by Mycobacterium tuberculosis. AB - Tuberculosis is a devastating contagious disease caused by Mycobacterium tuberculosis. This is the first report describing the development of novel capillary electrophoresis methods to detect lipoarabinomannans shed into the blood circulation by replicating bacteria. The novelty of the methods is the detection without derivatization. The lipoarabinomannan is detected owing to the ionization of the diverse functional groups of the structure, such as the multibranched mannan domain or the phosphatidyl group. Four alkaline solutions were used; normal polarity in three of them and reversed polarity in one. Urinary lipoarabinomannans by saccharide domains were identified with direct absorbance detection. The accuracy and the analytical sensitivity were then validated with cello-, manno- and xylooligosaccharides. Lipoarabinomannan detection was feasible within 20 min (RSD 2.1%). This method worked at the dynamic range of 0.1-10 MUg/mL. With reversed polarity, indirect absorbance detection, and pH 9.0 electrolyte were used, the analytes migrated already within 5 min (RSD 0.01%). Inorganic nonabsorbing ions were used for this method optimization. This improvement resulted in the detection limit of 1 pg/mL in water and in the linear dynamic range of 1 pg/mL to 10 ng/mL. In conclusion, the described method has great potential as a point-of-care assay for clinical use. PMID- 27196986 TI - Randomized Controlled Trial of Home-Based Hormonal Contraceptive Dispensing for Women At Risk of Unintended Pregnancy. AB - CONTEXT: Women frequently experience barriers to obtaining effective contraceptives from clinic-based providers. Allowing nurses to dispense hormonal methods during home visits may be a way to reduce barriers and improve -effective contraceptive use. METHODS: Between 2009 and 2013, a sample of 337 low-income, pregnant clients of a nurse home-visit program in Washington State were randomly selected to receive either usual care or enhanced care in which nurses were permitted to provide hormonal contraceptives postpartum. Participants were surveyed at baseline and every three months postpartum for up to two years. Longitudinal Poisson mixed-effects regression analysis was used to examine group differences in gaps in effective contraceptive use, and survival analysis was used to examine time until a subsequent pregnancy. RESULTS: Compared with usual care participants, enhanced care participants had an average of 9.6 fewer days not covered by effective contraceptive use during the 90 days following a first birth (52.6 vs. 62.2). By six months postpartum, 50% of usual care participants and 39% of enhanced care participants were using a long-acting reversible contraceptive (LARC). In analyses excluding LARC use, enhanced care participants had an average of 14.2 fewer days not covered by effective contraceptive use 0-3 months postpartum (65.0 vs. 79.2) and 15.7 fewer uncovered days 4-6 months postpartum (39.2 vs. 54.9). CONCLUSION: Home dispensing of hormonal contraceptives may improve women's postpartum contraceptive use and should be explored as an intervention in communities where contraceptives are not easily accessible. PMID- 27196987 TI - Preventive effects of simvastatin nanoliposome on isoproterenol-induced cardiac remodeling in mice. AB - In this study, simvastatin (SMV) and SMV nanoliposome (SMV-Lipo) were given to male BALB/c mice by either intragastric (i.g.) or intraperitoneal (i.p.) administration, and their effects on isoproterenol (ISO)-induced cardiac remodeling were compared. The results indicate that by i.p. administration, the SMV-Lipo at an equal SMV dose exhibited more significant inhibitory effects than the crude SMV on cardiac hypertrophy, fibrosis and inflammation. Comparing the SMV-Lipo on different administration regimens, i.p. group showed more significant inhibitory effects on cardiac remodeling than i.g. group. In addition, pharmacokinetic studies revealed that SMV-Lipo administrated by either i.p. or i.g. more significantly improved the plasma SMV concentration than the crude SMV. Therefore, the SMV-Lipo significantly enhanced the inhibitory effects of SMV on cardiac remodeling resulted from the enhanced absorption of SMV by nanoliposome formulation, and i.p. was better than i.g. administration. PMID- 27196988 TI - Systematic Review of Adverse Effects from Herbal Drugs Reported in Randomized Controlled Trials. AB - Herbal drugs have become a popular form of healthcare, raising concerns about their safety. This study aimed to characterize the adverse effects of herbal drugs through a systematic review of results reported in randomized controlled trials (RCTs). Using eight electronic databases including PubMed, the Cochrane library and six Korean medical databases, the frequency of reported toxicity was recorded based on drug composition and indication. Among 4957 potentially relevant articles, 242 papers comprised of 244 studies met our inclusion criteria; these included 111 studies of a single herb and 133 of multiple herbs. These studies accounted for a total 15 441 participants (male = 5590; female = 9851; 7383 for single and 8058 for multiple herb studies). There were 480 cases (3.1%) of adverse events (344 for single, 136 for multiple herb studies; p < 0.01). A total of 259 cases reported blood test abnormalities, including five cases of abnormality in hepatic functional enzymes. The most frequently reported adverse event was digestive symptoms (44.3%), followed by nervous system symptoms (17.3%) and behaviors such as loss of appetite (16.3%). This is the first systematic review of adverse effects of herbal drugs among clinical studies, and the results indicate that herbal drugs are relatively safe. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27196989 TI - Long-term trends of chemical characteristics and sources of fine particle in Foshan City, Pearl River Delta: 2008-2014. AB - Foshan is a major international ceramic center and the most polluted city in the Pearl River Delta (PRD). Here we present the results of the first long-term PM2.5 (particles <2.5MUm) sampling and chemical characterization study of the city. A total of 2774 samples were collected at six sites from 2008 to 2014, and analyzed for water soluble species, elements and carbonaceous species. The major constituents of PM2.5 were sulfate, OC (Organic Carbon), nitrate, ammonium and EC (Elemental Carbon), which accounted for 50%-88% of PM2.5. PM2.5 and the most abundant chemical species decreased from 2008 to 2011, but rebounded in 2012 2013. After 2008, the chemical composition of PM2.5 changed dramatically due to the implementation of pollution control measures. From 2008 to 2011, SO4(2-) and NO3(-) were the two largest components; subsequently, however, OC was the largest component. The respective contributions of SO4(2-), NO3(-) and OC to the sum of water soluble species and carbonaceous species were 30.5%, 22.9% and 19.9% in 2008; and 20.2%, 16.5% and 30.2% in 2014. Distinct differences in nitrate and sulfate, and in mass ratio [NO3(-)]/[SO4(2-)] imply that mobile sources tended to more important in Foshan during 2012-2014. The results indicate that pollution control measures implemented during 2008-2014 had a large effect on anthropogenic elements (Pb, As, Cd, Zn and Cu) and water soluble species, but little influence on crustal elements (V, Mn, Ti, Ba and Fe) and carbonaceous species. The PMF method was used for source apportionment of PM2.5. Industry (including the ceramic industry and coal combustion), vehicles and dust were the three most important sources and comprised 39.2%, 20.0% and 18.4% of PM2.5 in 2008, respectively. However, secondary aerosols, vehicles and industry were the three most important sources and comprised 29.5%, 22.4% and 20.4% of PM2.5 in 2014, respectively. During the seven year study interval, the contributions of primary sources (industry and dust) decreased significantly, but secondary sources increased dramatically. Industry, dust and vehicles contributed 36.6MUgm(-3), 13.9MUgm(-3), and 9.2MUgm(-3) to the reduction of PM2.5, respectively. PMID- 27196990 TI - "Is it still safe to eat traditional food?" Addressing traditional food safety concerns in aboriginal communities. AB - Food insecurity is a growing concern for indigenous communities worldwide. While the risk of heavy metal contamination associated to wild food consumption has been extensively studied in the Arctic, data are scarce for the Boreal zone. This study addressed the concerns over possible heavy metal exposure through consumption of traditional food in four Anishnaabeg communities living in the Eastern North American boreal forest. Liver and meat samples were obtained from 196 snowshoe hares (Lepus americanus) trapped during winter 2012 across the traditional lands of the participating communities and within 56-156km of a copper smelter. Interviews were conducted with 78 household heads to assess traditional food habits, focusing on snowshoe hare consumption. Concentrations in most meat and liver samples were below the detection limit for As, Co, Cr, Ni and Pb. Very few meat samples had detectable Cd and Hg concentrations, but liver samples had mean dry weight concentrations of 3.79mg/kg and 0.15mg/kg respectively. Distance and orientation from the smelter did not explain the variability between samples, but percent deciduous and mixed forest cover had a marginal negative effect on liver Cd, Cu and Zn concentrations. The estimated exposition risk from snowshoe hare consumption was low, although heavy consumers could slightly exceed recommended Hg doses. In accordance with the holistic perspective commonly adopted by indigenous people, the nutritional and sociocultural importance of traditional food must be considered in risk assessment. Traditional food plays a significant role in reducing and preventing serious health issues disproportionately affecting First Nations, such as obesity, diabetes, and cardiovascular diseases. PMID- 27196991 TI - Soil organic carbon of an intensively reclaimed region in China: Current status and carbon sequestration potential. AB - Land reclamation has been highly intensive in China, resulting in a large amount of soil organic carbon (SOC) loss to the atmosphere. Evaluating the factors which drive SOC dynamics and carbon sequestration potential in reclaimed land is critical for improving soil fertility and mitigating global warming. This study aims to determine the current status and factors important to the SOC density in a typical reclaimed land located in Eastern China, where land reclamation has been undergoing for centuries. A total of 4746 topsoil samples were collected from 2007 to 2010. The SOC density of the reclaimed land (3.18+/-0.05kgCm(-2); mean+/-standard error) is significantly lower than that of the adjacent non reclaimed land (5.71+/-0.04kgCm(-2)) (p<0.05). A Random Forest model is developed and it captures the relationships between the SOC density and the environmental/anthropogenic factors (R(2)=0.59). The soil pH, land use, and elevation are the most important factors for determining SOC dynamics. In contrast, the effect of the reclamation age on the SOC density is negligible, where SOC content in the land reclaimed during years 1047-1724 is as low as that reclaimed during years 1945-2004. The scenario analysis results indicate that the carbon sequestration potential of the reclaimed lands may achieve a maximum of 5.80+/-1.81kgCO2m(-2) (mean+/-SD) when dryland is converted to flooded land with vegetable-rice cropping system and soil pH of ~5.9. Note that in some scenarios the methane emission substantially offsets the carbon sequestration potential, especially for continuous rice cropping system. With the optimal setting for carbon sequestration, it is estimated that the dryland reclaimed in the last 50years in China is able to sequester 0.12milliontons CO2 equivalent per year. PMID- 27196993 TI - Spiritual well-being and spiritual distress predict adjustment in adolescent and young adult cancer survivors. AB - OBJECTIVE: Spirituality is related to many aspects of cancer survivors' physical and psychological adjustment. Given their unique developmental issues, spiritual issues may be especially important to adolescent and young adult (AYA) survivors, yet little research has been conducted on spirituality with AYA survivors. The present study examines how two aspects of spirituality, spiritual well-being (comprising faith and meaning/peace), and spiritual struggle relate to later post cancer adjustment. METHODS: At Time 1 (T1), 120 AYA survivors completed questionnaires on spirituality and adjustment (fear of recurrence, post-traumatic stress symptoms, perceived post-traumatic growth, psychological distress, and health-related quality of life). Eighty-three of these participants also completed these questionnaires at Time 2 (T2), one year later. RESULTS: Our sample reported fairly low spiritual well-being (meaning/peace, faith) and spiritual struggle. As expected, T1 spiritual well-being was positively correlated with some aspects of psychological adjustment at T2, whereas T1 spiritual struggle was inversely correlated with T2 psychological adjustment. Both dimensions of T1 spiritual well-being, but not struggle, were positively associated with perceived T2 posttraumatic growth. In general, T1 spiritual well being and struggle correlated with T2 psychological adjustment even when demographics and cancer-related variables were controlled. CONCLUSIONS: These results suggest that while spirituality is not important to all AYA survivors, both spiritual well-being and struggle have important associations with adjustment and may warrant clinical attention. Future research is needed to more fully understand the role of spirituality in AYA survivors' adjustment in more depth. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27196992 TI - Bioaccessibility and arsenic speciation in carrots, beets and quinoa from a contaminated area of Chile. AB - Consumption of vegetables grown in arsenic (As)-contaminated soils is an important exposure route to the element for humans. The present study is focused on locally-grown, frequently-consumed vegetables, such as carrots (Daucus carota), beets (Beta vulgaris) and quinoa (Chenopodium) from the As-polluted Chiu Chiu area in Northern Chile. The latter region is affected both by As discharge from copper mining activity and natural As contamination, leading to a high As content in local food and water. For the selected vegetables, the following aspects were investigated: i) Their total As, Cu, Pb, Cr, Cd and Mn content; ii) Arsenic speciation in the edible part of the vegetables by liquid chromatography inductively-coupled plasma mass spectrometry (LC-ICPMS) analysis; iii) Arsenic bioaccessibility in the vegetables during in vitro gastrointestinal digestion; iv) Arsenic species present in the extracts obtained from in vitro gastrointestinal digestion; and v) Arsenic dietary exposure estimates for the assessment of the risk posed by the vegetables consumption. A significant degree of As contamination was found in the vegetables under study, their metal content having been compared with that of similar Spanish uncontaminated products. In vitro gastrointestinal digestion of the studied vegetables led to quantitative extraction of As from carrots and beets, whereas efficiency was about 40% for quinoa. For carrots, only As(III) and As(V) species were found, being their concentration levels similar. In the case of quinoa, around 85% of the element was present as As(V). For beets, inorganic As(V) and unknown overlapped As species (probably arsenosugars) were found. No significant transformation of the original As species was observed during in vitro gastrointestinal digestion. Arsenic dietary exposure values obtained for the three vegetables (0.017-0.021MUg As person(-1)day(-1)) were much lower than the JFCFA's safety limit of 50MUg As person(-1)day(-1). Therefore, no toxicological risk would be expected from the intake of these vegetables. PMID- 27196995 TI - Evaluation of the Role of Umbilical Cord Serum and Autologous Serum Therapy in Reepithelialization After Keratoplasty: A Randomized Controlled Clinical Trial. AB - PURPOSE: To evaluate the role of umbilical cord serum (UCS) and autologous serum (AS) therapy in reepithelialization of corneal graft after keratoplasty in a randomized controlled trial. METHODS: A total of 105 eyes with epithelial defect (ED) after keratoplasty (penetrating keratoplasty-67 and anterior lamellar keratoplasty-38) on the first postoperative day were included in the study. The eyes were randomized into three groups: UCS (n=35), AS (n=35), and artificial tears (AT) (n=35). All patients received standard postoperative medical therapy. The primary outcome measure was time to epithelialization, and secondary outcome measures were best-corrected visual acuity and graft clarity. RESULTS: The ED healed completely in 103 eyes. The mean time for complete reepithelialization was 2.5+/-2.1, 3.1+/-2.2, and 4.5+/-1.4 days in UCS, AS, and AT groups, respectively. The mean percentage decrease in the size of the ED was significantly better in the UCS and AS groups as compared with the AT group (P=0.001). The rate of reepithelialization was comparable between the AS and UCS groups (P=0.3). On bivariate analysis, significant correlation was found between the mean size of postoperative ED, grade of the donor cornea (P=0.001), and the presence of preoperative ED (P=0.001). No complications were associated with the use of serum therapy. CONCLUSION: Most of the cases of postkeratoplasty corneal ED can be managed with AT only. The serum therapy (AS/UCS) helps in the faster reepithelialization of postkeratoplasty ED as compared with AT and may be considered as a treatment option for early epithelial healing. PMID- 27196994 TI - Corneal Thickness Profile Changes After Femtosecond LASIK for Hyperopia. AB - PURPOSE: To compare changes in the corneal thickness profile before and 6 months after femtosecond laser in situ keratomileusis (LASIK) for hyperopia. METHODS: In a prospective noncomparative case series study, 24 eyes of 20 hyperopic patients undergoing femtosecond LASIK were examined preoperatively and 6 months postoperatively. Corneal profile was measured using Pentacam HR device. Paired t test was used to compare preoperative and postoperative values. Spearman correlation analysis was performed to evaluate the relationship between the central corneal thickness changes and attempted spherical equivalent refraction (SER). RESULTS: The mean uncorrected distance visual acuity significantly improved after surgery (P<0.001). Significant differences in central, midperipheral, ablative annular, and peripheral corneal thicknesses were observed from preoperatively to 6 months postoperatively (all P<0.001). There was no significant correlation between the changes in the central corneal thickness and attempted SER (P=0.23). CONCLUSIONS: The corneal thicknesses across the whole ablation zone including central corneal thickness, significantly decrease postoperatively compared with preoperatively. PMID- 27196996 TI - Cosmetic Cleansing Oil Absorption by Soft Contact Lenses in Dry and Wet Conditions. AB - OBJECTIVES: Previous reports showed that cosmetic cleansing oil for removing makeup, which contains mineral oil and surfactant, can deform some silicone hydrogel contact lenses (SHCLs) when applied directly to the lenses, although plasma-coated SHCLs (lotrafilcon A and B) were not affected. In the present study, we investigated hydrogel lenses and SHCLs in both wet and dry conditions. METHODS: Several brands of hydrogel and SHCLs were immersed in a cleansing oil solution containing Sudan Black B for 5 min under wet and dry conditions. The lenses under the wet condition were simply picked up from the saline, whereas those under the dry condition were blotted with paper wipes. After immersing, the excess solution remaining on the lenses was removed by finger rubbing with a multipurpose solution. The lenses were then examined using a stereomicroscope, and their mean brightness was measured and compared. RESULTS: The cosmetic cleansing oil was not absorbed by the hydrogel lenses under wet or dry conditions. However, four of seven brands of SHCLs absorbed the cosmetic cleansing oil under both conditions (dry and wet), whereas asmofilcon A absorbed it only under the dry condition. Lotrafilcon B and delefilcon A did not absorb cleansing oil even under the dry condition. CONCLUSIONS: Hydrogel lenses resist cosmetic cleansing oil. However, SHCLs have different degrees of resistance depending on the lens material. Some SHCLs absorbed cosmetic cleansing oil more under dry conditions than under wet conditions. PMID- 27196997 TI - Heparin-Based Coacervate of FGF2 Improves Dermal Regeneration by Asserting a Synergistic Role with Cell Proliferation and Endogenous Facilitated VEGF for Cutaneous Wound Healing. AB - Effective wound healing requires complicated, coordinated interactions and responses at protein, cellular, and tissue levels involving growth factor expression, cell proliferation, wound closure, granulation tissue formation, and vascularization. In this study, we develop a heparin-based coacervate consisting of poly(ethylene argininylaspartate digylceride) (PEAD) as a storage matrix, heparin as a bridge, and fibroblast growth factor-2 (FGF2) as a cargo (namely heparin-FGF2@PEAD) for wound healing. First, in vitro characterization demonstrates the loading efficiency and control release of FGF2 from the heparin FGF2@PEAD coacervate. The following in vivo studies examine the wound healing efficiency of the heparin-FGF2@PEAD coacervate upon delivering FGF2 to full thickness excisional skin wounds in vivo, in comparison with the other three control groups with saline, heparin@PEAD as vehicle, and free FGF2. Collective in vivo data show that controlled release of FGF2 to the wounds by the coacervate significantly accelerates the wound healing by promoting cell proliferation, stimulating the secretion of vascular endothelial growth factor (VEGF) for re epithelization, collagen deposition, and granulation tissue formation, and enhancing the expression of platelet endothelial cell adhesion molecule (CD31) and alpha-smooth muscle actin (alpha-SMA) for blood vessel maturation. In parallel, no obvious wound healing effect is found for the control, vehicle, and free FGF2 groups, indicating the important role of the coavervate in the wound healing process. This work designs a suitable delivery system that can protect and release FGF2 in a sustained and controlled manner, which provides a promising therapeutic potential for topical treatment of wounds. PMID- 27196998 TI - P2Y12 receptor inhibition and effect of morphine in patients undergoing primary PCI for ST-segment elevation myocardial infarction. The PRIVATE-ATLANTIC study. AB - PRIVATE-ATLANTIC (P2Y12 Receptor Inhibition with VASP Testing using Elisa kit during the ATLANTIC study) is a pre-specified substudy of the randomised, double blind ATLANTIC trial in patients with ST-segment elevation myocardial infarction, designed to help interpret the main trial results. The primary objective of ATLANTIC was to assess coronary reperfusion prior to percutaneous coronary intervention (PCI) with pre- vs in-hospital ticagrelor 180 mg loading dose (LD). PRIVATE-ATLANTIC assessed platelet inhibition in 37 patients by measurement of vasodilator-associated stimulated phosphoprotein (VASP) platelet reactivity index (PRI) and VerifyNow platelet reactivity units (PRU) before angiogram (T1), immediately after PCI (T2), 1 (T3), and 6 (T4) hours (h) after PCI, and before next study drug administration (T5). The median time difference between the two ticagrelor LD was 41 minutes. Platelet reactivity was unaffected at T1 when measured by VASP-PRI (89.8 vs 93.9 % for pre- and in-hospital ticagrelor, respectively; p = 0.18) or PRU (239 vs 241; p = 0.82). Numerical differences were apparent at T2 and maximal at T3. Morphine administration significantly delayed onset of platelet inhibition at T3 (VASP-PRI 78.2 vs 23.4 % without morphine; p = 0.0116) and T4 (33.1 vs 11.0 %; p = 0.0057). In conclusion, platelet inhibition in ATLANTIC was unaffected by pre-hospital ticagrelor administration at the time of initial angiogram due to the short transfer delay. The maximum difference in platelet inhibition was detected 1 h after PCI (T3). Morphine administration was associated with delayed onset of action of ticagrelor and appeared more important than timing of ticagrelor administration. PMID- 27196999 TI - Medical Need, Equality, and Uncertainty. AB - Many hold that distributing healthcare according to medical need is a requirement of equality. Most egalitarians believe, however, that people ought to be equal on the whole, by some overall measure of well-being or life-prospects; it would be a massive coincidence if distributing healthcare according to medical need turned out to be an effective way of promoting equality overall. I argue that distributing healthcare according to medical need is important for reducing individuals' uncertainty surrounding their future medical needs. In other words, distributing healthcare according to medical need is a natural feature of healthcare insurance; it is about indemnity, not equality. PMID- 27197001 TI - Errata: Vol. 65, No. 18. AB - In the report, "Progress Toward Polio Eradication - Worldwide, 2015-2016," on page 471, in Table 2, the title should have read "Number of reported poliovirus cases, by country - worldwide, January 1, 2015-May 4, 2016," and the heading for the second column should have been "2015 (January-December)." PMID- 27197000 TI - Clinical significance of pulse pressure in patients with heart failure with preserved left ventricular ejection fraction. AB - AIMS: Although pulse pressure (PP) is a recognized risk factor for various cardiovascular diseases, its association with cardiovascular outcomes in patients with heart failure with preserved ejection fraction (HFpEF) is uncertain. METHODS AND RESULTS: We enrolled 512 of 951 consecutive HFpEF patients admitted to the Kumamoto University Hospital between 2007 and 2013 and divided them into five groups according to PP quintiles. Blood pressure and pulse wave velocity (PWV) were measured by an ankle-brachial index device. The PP values in HFpEF were significantly and positively correlated with PWV and LV stroke volume index, and were negatively correlated with estimated glomerular filtration rate and haemoglobin levels. Furthermore, plasma B-type natriuretic peptide levels in HFpEF patients with the lowest (<45 mmHg) and highest PP (>=75 mmHg) were significantly higher than those with other PP (45-74 mmHg). The percentage of total cardiovascular and heart failure (HF)-related events by PP category resulted in U- and J-shaped curves. The higher frequency of coronary-related events was nearly linear. In the Kaplan-Meier analysis, HFpEF patients with the lowest and highest PP quintiles had a significantly higher risk of cardiovascular and HF-related events than those with other PPs (45-74 mmHg) (log-rank test, both P < 0.01). Conversely, the frequency of coronary-related events in the highest PP group, but not in the lowest PP group, was significantly higher than in other PP groups. CONCLUSION: Pulse pressure lower than 45 mmHg and higher than 75 mmHg was closely associated with HFpEF prognosis, indicating the clinical significance of PP for risk stratification of HFpEF. PMID- 27197002 TI - Safety and Efficacy of Different Catheter Ablations for Atrial Fibrillation: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Previous studies suggested that cryoballoon ablation had clinical benefits comparable to those of radiofrequency ablation. However, recently, some new catheters have been invented, and no universal consensus exists on which ablation is the optimal choice. The present systematic review and meta-analysis aimed to assess and compare the safety and efficacy of cryoballoon and radiofrequency ablation by synthesizing published trials. METHODS AND RESULTS: A systematic literature review was conducted searching Medline, PubMed, Embase, Cochrane Library, and so forth. All trials comparing cryoballoon and radiofrequency ablation were screened and included if inclusion criteria were met. A total of 40 eligible studies were identified, adding up to 11,395 patients. The follow-up period ranged from 3 months to 25 months. Overall analyses indicated that cryoballoon ablation could bring more benefit in procedural time (risk ratio [RR] = -0.39, 95% confidence interval [CI]: -0.62 to 0.15), atrial fibrillation (AF) recrudescence (RR = 0.82, 95% CI: 0.70-0.96), and major complications (RR = 0.74, 95% CI: 0.58-0.95) for patients with AF. For the subgroups, the first-generation cryoballoon significantly reduced procedural time and major complications, but it increased ablation time. The patients referred for the second-generation cryoballoon (CBA) seemed to receive more clinical benefit (procedural time, fluoroscopic time, ablation time, AF recrudescence) and fewer complications. Finally, multiparty catheter (MTCA) was found to significantly reduce procedural and fluoroscopic times with a high rate of AF recrudescence. CONCLUSIONS: The present systematic review and meta-analysis demonstrated that cryoballoon ablation was associated with greater freedom from AF, shorter procedural time, and lower rate of major complications, compared with radiofrequency ablation. Especially, CBA was more advantageous. However, MTCA seems promising for radiofrequency ablation. PMID- 27197004 TI - Accuracy and Utility of Self-report of Refractive Error. AB - IMPORTANCE: Large-scale generic studies offer detailed information on potential risk factors for refractive error across the life course, but ophthalmic examination in such cases to determine the refractive error phenotype is challenging and costly. Thus, refractive status is commonly assigned using questionnaires. In a population survey, often only a few condition-specific self reported questions can be included, so the questions used must be effective in ruling in those who have the trait of interest and ruling out those who do not. OBJECTIVE: To determine the accuracy of identification of refractive status using self-reported age at and/or reason for first use of glasses or contact lenses (optical correction). DESIGN, SETTING, AND PARTICIPANTS: The UK Biobank study, a cross-sectional epidemiologic study, included 117 278 participants aged 40 to 69 years in 6 regional centers in England and Wales. Data for the present study were assessed from June 2009 to July 2010. Patients underwent autorefraction measurement. Spherical equivalent in the more extreme eye was used to categorize myopia (-1.00 diopter [D] or more extreme) and hypermetropia (+1.00 D or more extreme). MAIN OUTCOMES AND MEASURES: Sensitivity and specificity of the reason for optical correction were assessed using autorefraction as the gold standard. Receiver operating characteristic curves assessed the accuracy of self-reported age at first use of optical correction and incremental improvement with addition of the reason. RESULTS: Of the 95 240 participants who reported using optical correction (55.6% female; mean [SD] age, 57.7 [7.5] years), 92 121 (96.7%) provided their age at first use and 93 156 (97.8%) provided the reason. For myopia, sensitivity of the reason for optical correction was 89.1% (95% CI, 88.7% 89.4%), specificity was 83.7% (95% CI, 83.4%-84.0%), and positive and negative predictive values were 72.7% (95% CI, 72.2%-73.1%) and 94.0% (95% CI, 93.8% 94.2%), respectively. The area under the curve was 0.829 (95% CI, 0.826-0.831) and improved to 0.928 (95% CI, 0.926-0.930) with combined information. By contrast, self-report of the reason for optical correction of hypermetropia had low sensitivity (38.1%; 95% CI, 37.6%-38.6%), and the area under the curve with combined information was 0.713 (95% CI, 0.709-0.716). CONCLUSIONS AND RELEVANCE: In combination, self-report of the reason for and age at first use of optical correction are accurate in identifying myopia. These findings indicate an agreed set of questions could be implemented effectively in large-scale generic population-based studies to increase opportunities for integrated research on refractive error leading to development of novel prevention or treatment strategies. PMID- 27197005 TI - Enacting simulation: A sociomaterial perspective on students' interprofessional collaboration. AB - Full-scale simulation exercises are becoming more common as an educational feature of the undergraduate training of health professionals. This study explores how interprofessional collaboration is enacted by the participating students. Practice theory is used as the theoretical framework for a field study of two naturalistic educational settings, when medical and nursing students come together to practice in a simulated emergency situation, where a manikin is replacing the patient. Eighteen sessions of simulations were observed, and data were collected through standardised video recordings that were analysed collaboratively. To ensure transparency and scientific rigour, a stepwise constant comparative analysis was conducted, in which individual observations within and across single video recordings were compared, negotiated and eventually merged. The findings show that the student teams relate to the manikin as a technical, medical, and human body, and that interprofessional knowings and enactments emerge as a fluid movement between bodily positioning in synchrony and bodily positioning out of synchrony in relation to the sociomaterial arrangements. The findings are related to contemporary theorisations of practice comprising an integrated view of body and mind, and it is discussed how the findings can be used in simulation exercises to support participants' learning in new ways. PMID- 27197007 TI - Management of plastic bronchitis after Fontan operation with resolution of symptoms. PMID- 27197006 TI - Clopidogrel allergy successfully treated with corticosteroids without clopidogrel withdrawal. PMID- 27197008 TI - Diagnostic challenges in a long-term follow-up of hypereosinophilic restrictive cardiomyopathy. PMID- 27197003 TI - Recommendations for genetic testing to reduce the incidence of anthracycline induced cardiotoxicity. AB - AIMS: Anthracycline-induced cardiotoxicity (ACT) occurs in 57% of treated patients and remains an important limitation of anthracycline-based chemotherapy. In various genetic association studies, potential genetic risk markers for ACT have been identified. Therefore, we developed evidence-based clinical practice recommendations for pharmacogenomic testing to further individualize therapy based on ACT risk. METHODS: We followed a standard guideline development process, including a systematic literature search, evidence synthesis and critical appraisal, and the development of clinical practice recommendations with an international expert group. RESULTS: RARG rs2229774, SLC28A3 rs7853758 and UGT1A6 rs17863783 variants currently have the strongest and the most consistent evidence for association with ACT. Genetic variants in ABCC1, ABCC2, ABCC5, ABCB1, ABCB4, CBR3, RAC2, NCF4, CYBA, GSTP1, CAT, SULT2B1, POR, HAS3, SLC22A7, SCL22A17, HFE and NOS3 have also been associated with ACT, but require additional validation. We recommend pharmacogenomic testing for the RARG rs2229774 (S427L), SLC28A3 rs7853758 (L461L) and UGT1A6*4 rs17863783 (V209V) variants in childhood cancer patients with an indication for doxorubicin or daunorubicin therapy (Level B - moderate). Based on an overall risk stratification, taking into account genetic and clinical risk factors, we recommend a number of management options including increased frequency of echocardiogram monitoring, follow-up, as well as therapeutic options within the current standard of clinical practice. CONCLUSIONS: Existing evidence demonstrates that genetic factors have the potential to improve the discrimination between individuals at higher and lower risk of ACT. Genetic testing may therefore support both patient care decisions and evidence development for an improved prevention of ACT. PMID- 27197009 TI - Abdominal pain: diagnostic issues in patient with coexisting Takayasu's arteritis and ulcerative colitis. PMID- 27197010 TI - [Compendium for performing and describing the resting electrocardiogram. Diagnostic criteria describe rhythm, electrical axis of the heart, QRS voltage, automaticity and conduction disorders. Experts' group statement of the Working Group on Noninvasive Ele]. PMID- 27197011 TI - Is MIBG really of no use in the diagnosis of heart failure? PMID- 27197012 TI - Commentary to the article: "Rivaroxaban in secondary cardiogenic stroke prevention: two-year single-centre experience based on follow-up of 209 patients". PMID- 27197013 TI - Response to the letter concerning the article "Rivaroxaban in secondary cardiogenic stroke prevention: two-year single-centre experience based on follow up of 209 patients". PMID- 27197014 TI - Interrogating the Druggability of the 2-Oxoglutarate-Dependent Dioxygenase Target Class by Chemical Proteomics. AB - The 2-oxoglutarate-dependent dioxygenase target class comprises around 60 enzymes including several subfamilies with relevance to human disease, such as the prolyl hydroxylases and the Jumonji-type lysine demethylases. Current drug discovery approaches are largely based on small molecule inhibitors targeting the iron/2 oxoglutarate cofactor binding site. We have devised a chemoproteomics approach based on a combination of unselective active-site ligands tethered to beads, enabling affinity capturing of around 40 different dioxygenase enzymes from human cells. Mass-spectrometry-based quantification of bead-bound enzymes using a free ligand competition-binding format enabled the comprehensive determination of affinities for the cosubstrate 2-oxoglutarate and for oncometabolites such as 2 hydroxyglutarate. We also profiled a set of representative drug-like inhibitor compounds. The results indicate that intracellular competition by endogenous cofactors and high active site similarity present substantial challenges for drug discovery for this target class. PMID- 27197018 TI - Evidence of Mycobacterium tuberculosis complex bacteraemia in intradermal skin test positive cattle detected using phage-RPA. AB - Bovine tuberculosis is a zoonotic infectious disease caused by Mycobacterium bovis that affects cattle and can cause tuberculosis in a range of wildlife animals. A bacteriophage-based method combined with PCR (phage-PCR) has been recently used to detect and identify viable pathogenic mycobacteria in the peripheral blood mononuclear cells (PBMCs) of animals suffering from paratuberculosis. To adapt this method for the detection of M. bovis in blood, a new isothermal DNA amplification protocol using Recombinase Polymerase Amplification (RPA) was developed and was found to be able to detect M. bovis BCG within 48 h, with a limit of detection of approximately 10 cells per ml of blood for artificially inoculated blood samples. When blood samples (2 ml) from a Single Comparative Cervical Intradermal Tuberculin (SCCIT)- negative beef herd were tested, Mycobacterium tuberculosis complex (MTC) cells were not detected from any (45) of the blood samples. However when blood samples from SCCIT positive animals were tested, viable MTC bacteria were detected in 66 % (27/41) of samples. Of these 41 animals sampled, 32 % (13) had visible lesions. In the visible lesion (VL) group, 85 % (11/13) had detectable levels of MTC whereas only 57 % (16/28) of animals which had no visible lesions (NVL) were found to have detectable mycobacteraemia. These results indicated that this simple, rapid method can be applied for the study of M. bovis infections. The frequency with which viable mycobacteria were detected in the peripheral blood of SCCIT-positive animals changes the paradigm of this disease. PMID- 27197020 TI - Comparing Single Versus Double Screw-Rod Anterior Instrumentation for Treating Thoracolumbar Burst Fractures with Incomplete Neurological Deficit: A Prospective, Randomized Controlled Trial. AB - BACKGROUND Following a thoracolumbar burst fracture (TCBF), anterior screw-rods apply pressure upon the graft site. However, there is limited evidence comparing single screw-rod anterior instrumentation (SSRAI) to double screw-rod anterior instrumentation (DSRAI) for TCBFs. Our objective was to compare SSRAI versus DSRAI for TCBFs with incomplete neurological deficit. MATERIAL AND METHODS A total of 51 participants with T11-L2 TCBFs (AO classification: A3) were randomly assigned to receive SSRAI or DSRAI. Key preoperative, perioperative, and postoperative data were collected. Statistical analysis was conducted to determine the independent factors associated with inferior clinical outcomes, as well as the comparative efficacy of SSRAI and DSRAI. RESULTS There were no significant differences in the key demographic and clinical characteristics between the two groups (all p>0.05). Smoking status was significantly associated with inferior three-month and six-month Denis pain scores (Wald statistic=4.246, p=0.039). Both SSRAI and DSRAI were significantly effective in improving three month and six-month postoperative degree of kyphosis, three-month and six-month postoperative ASIA impairment scale scores, three-month and six-month postoperative Denis pain score, and three-month and six-month postoperative Denis work score (all p<0.001). Although there were no significant differences between DSRAI and SSRAI with respect to all outcomes (all p>0.05), DSRAI displayed significantly longer operating times, as well as significantly larger operative blood losses (both p<0.001). CONCLUSIONS SSRAI may be preferable over DSRAI for TCBFs with incomplete neurological deficit due to its lower operating time and amount of operative blood loss. PMID- 27197019 TI - High-resolution characterization of a PACAP-EGFP transgenic mouse model for mapping PACAP-expressing neurons. AB - Pituitary adenylate cyclase-activating polypeptide (PACAP, gene name Adcyap1) regulates a wide variety of neurological and physiological functions, including metabolism and cognition, and plays roles in of multiple forms of stress. Because of its preferential expression in nerve fibers, it has often been difficult to trace and identify the endogenous sources of the peptide in specific populations of neurons. Here, we introduce a transgenic mouse line that harbors in its genome a bacterial artificial chromosome containing an enhanced green fluorescent protein (EGFP) expression cassette inserted upstream of the PACAP ATG translation initiation codon. Analysis of expression in brain sections of these mice using a GFP antibody reveals EGFP expression in distinct neuronal perikarya and dendritic arbors in several major brain regions previously reported to express PACAP from using a variety of approaches, including radioimmunoassay, in situ hybridization, and immunohistochemistry with and without colchicine. EGFP expression in neuronal perikarya was modulated in a manner similar to PACAP gene expression in motor neurons after peripheral axotomy in the ipsilateral facial motor nucleus in the brainstem, providing an example in which the transgene undergoes proper regulation in vivo. These mice and the high-resolution map obtained are expected to be useful in understanding the anatomical patterns of PACAP expression and its plasticity in the mouse. J. Comp. Neurol. 524:3827-3848, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27197021 TI - Determinants of bird conservation-action implementation and associated population trends of threatened species. AB - Conservation actions, such as habitat protection, attempt to halt the loss of threatened species and help their populations recover. The efficiency and the effectiveness of actions have been examined individually. However, conservation actions generally occur simultaneously, so the full suite of implemented conservation actions should be assessed. We used the conservation actions underway for all threatened and near-threatened birds of the world (International Union for Conservation of Nature Red List of Threatened Species) to assess which biological (related to taxonomy and ecology) and anthropogenic (related to geoeconomics) factors were associated with the implementation of different classes of conservation actions. We also assessed which conservation actions were associated with population increases in the species targeted. Extinction-risk category was the strongest single predictor of the type of conservation actions implemented, followed by landmass type (continent, oceanic island, etc.) and generation length. Species targeted by invasive nonnative species control or eradication programs, ex situ conservation, international legislation, reintroduction, or education, and awareness-raising activities were more likely to have increasing populations. These results illustrate the importance of developing a predictive science of conservation actions and the relative benefits of each class of implemented conservation action for threatened and near threatened birds worldwide. PMID- 27197023 TI - Bowel Radiation Injury: Complexity of the Pathophysiology and Promises of Cell and Tissue Engineering. AB - Ionizing radiation is effective to treat malignant pelvic cancers, but the toxicity to surrounding healthy tissue remains a substantial limitation. Early and late side effects not only limit the escalation of the radiation dose to the tumor but may also be life-threatening in some patients. Numerous preclinical studies determined specific mechanisms induced after irradiation in different compartments of the intestine. This review outlines the complexity of the pathogenesis, highlighting the roles of the epithelial barrier in the vascular network, and the inflammatory microenvironment, which together lead to chronic fibrosis. Despite the large number of pharmacological molecules available, the studies presented in this review provide encouraging proof of concept regarding the use of mesenchymal stromal cell (MSC) therapy to treat radiation-induced intestinal damage. The therapeutic efficacy of MSCs has been demonstrated in animal models and in patients, but an enormous number of cells and multiple injections are needed due to their poor engraftment capacity. Moreover, it has been observed that although MSCs have pleiotropic effects, some intestinal compartments are less restored after a high dose of irradiation. Future research should seek to optimize the efficacy of the injected cells, particularly with regard to extending their life span in the irradiated tissue. Moreover, improving the host microenvironment, combining MSCs with other specific regenerative cells, or introducing new tissue engineering strategies could be tested as methods to treat the severe side effects of pelvic radiotherapy. PMID- 27197022 TI - Axon degeneration: context defines distinct pathways. AB - Axon degeneration is an essential part of development, plasticity, and injury response and has been primarily studied in mammalian models in three contexts: 1) Axotomy-induced Wallerian degeneration, 2) Apoptosis-induced axon degeneration (axon apoptosis), and 3) Axon pruning. These three contexts dictate engagement of distinct pathways for axon degeneration. Recent advances have identified the importance of SARM1, NMNATs, NAD+ depletion, and MAPK signaling in axotomy induced Wallerian degeneration. Interestingly, apoptosis-induced axon degeneration and axon pruning have many shared mechanisms both in signaling (e.g. DLK, JNKs, GSK3alpha/beta) and execution (e.g. Puma, Bax, caspase-9, caspase-3). However, the specific mechanisms by which caspases are activated during apoptosis versus pruning appear distinct, with apoptosis requiring Apaf-1 but not caspase-6 while pruning requires caspase-6 but not Apaf-1. PMID- 27197024 TI - Historical Improvement in Speed Skating Economy. AB - : Half the improvement in 1500-m speed-skating world records can be explained by technological innovations and the other half by athletic improvement. It is hypothesized that improved skating economy is accountable for much of the athletic improvement. PURPOSE: To determine skating economy in contemporary athletes and to evaluate the change in economy over the years. METHODS: Contemporary skaters of the Dutch national junior team (n = 8) skated 3 bouts of 6 laps at submaximal velocity, from which skating economy was calculated (in mL O2 ? kg-1 ? km-1). A literature search provided historic data on skating velocity and submaximal VO2 (in mL ? kg-1 ? min-1), from which skating economy was determined. The association between year and skating economy was determined using linear-regression analysis. Correcting the change in economy for technological innovations resulted in an estimate of the association between year and economy due to athletic improvement. RESULTS: A mean (+/- SD) skating economy of 73.4 +/- 6.4 mL O2 ? kg-1 ? km-1 was found in contemporary athletes. Skating economy improved significantly over the historical time frame (-0.57 mL O2 ? kg-1 ? km-1 ? y-1, 95% confidence interval [-0.84, -0.31]). In the final regression model for the klapskate era, with altitude as confounder, skating economy improved with a nonsignificant -0.58 mL O2 ? kg-1 ? km-1 ? y-1 ([-1.19, 0.035]). CONCLUSIONS: Skating economy was 73.4 +/- 6.4 mL O2 ? kg-1 ? km-1 in contemporary athletes and improved over the past ~50 y. The association between year and skating economy due to athletic improvement, for the klapskate era, approached significance, suggesting a possible improvement in economy over these years. PMID- 27197025 TI - Dry conditions disrupt terrestrial-aquatic linkages in northern catchments. AB - Aquatic ecosystems depend on terrestrial organic matter (tOM) to regulate many functions, such as food web production and water quality, but an increasing frequency and intensity of drought across northern ecosystems is threatening to disrupt this important connection. Dry conditions reduce tOM export and can also oxidize wetland soils and release stored contaminants into stream flow after rainfall. Here, we test whether these disruptions to terrestrial-aquatic linkages occur during mild summer drought and whether this affects biota across 43 littoral zone sites in 11 lakes. We use copper (Cu) and nickel (Ni) as representative contaminants, and measure abundances of Hyalella azteca, a widespread indicator of ecosystem condition and food web production. We found that tOM concentrations were reduced but correlations with organic soils (wetlands and riparian forests) persisted during mild drought and were sufficient to suppress labile Cu concentrations. Wetlands, however, also became a source of labile Ni to littoral zones, which was linked to reduced abundances of the amphipod H. azteca, on average by up to 70 times across the range of observed Ni concentrations. This reveals a duality in the functional linkage of organic soils to aquatic ecosystems whereby they can help buffer the effects of hydrologic disconnection between catchments and lakes but at the cost of biogeochemical changes that release stored contaminants. As evidence of the toxicity of trace contaminant concentrations and their global dispersion grows, sustaining links among forests, organic soils and aquatic ecosystems in a changing climate will become increasingly important. PMID- 27197026 TI - Association of Notch4 with metastasis in human oral squamous cell carcinoma. AB - AIMS: Despite the development of several therapeutic strategies in the past decades, clinicians have failed to improve the survival rate of oral squamous cell carcinoma patients due to the highly metastatic nature of the disease and its high recurrence rate. However, there is accumulating evidence that aberrant Notch4 expression has a critical role in tumorigenesis but its prognostic value and function in OSCC remains uncertain. This study therefore investigates (1) the expression of Notch4 and its downstream target, myelin associated glycoprotein (MAG) in tissue samples representative of different stages of OSCC with varied clinicopathological features and (2) the possible involvement of Notch4 in the proliferation and migration of OSCC cells. MAIN METHODS: Sixty patients reported positive for OSCC were obtained along with the clinicopathological parameters and we performed immunohistochemistry, western blotting and RT-PCR for Notch4 and MAG expression. Further, the metastatic role of Notch4 was analyzed in the HSC-3 cell line by cell proliferation and migration assays. KEY FINDINGS: Our findings reveal that Notch4 and MAG expression are significantly upregulated in specifically late stages of OSCC tumor sections and perineural invasion (PNI) positive cases. In addition, depletion of Notch4 by siRNA inhibited the proliferative and migratory ability of the highly metastatic HSC-3 OSCC cells. SIGNIFICANCE: Our study indicates that the aberrant activation of Notch4 promotes OSCC metastasis through perineural spread and ascertains its value as a significant prognostic marker and potential therapeutic target to treat this highly aggressive malignancy. PMID- 27197027 TI - Time course investigation of intervertebral disc degeneration in a rat-tail puncture model. AB - AIMS: Intervertebral disc (IVD) degeneration was believed to contribute to lower back pain. The aim of the study was to investigate the pathogenesis and regulatory mechanism of puncture-induced IVD degeneration. MAIN METHODS: We established a rat-tail puncture model using Kirschner wire and a homemade stopper. The progress of disc degeneration was evaluated by histological examination and the quantitative measurement of type I, type II collagen and other factors expression at 0.5, 1, 2, 6, and 12weeks after puncture and was compared with control rats of the same age. KEY FINDINGS: Histological examination and Safranin-O staining revealed progressive degeneration of the punctured disc. Matrix metalloproteinase 13 (MMP13) was increased at 1week after puncture but did not change in the control group. The interleukin-1 beta (IL 1beta) mRNA expression level was elevated at the acute stage after puncture compared with the control group. The hypoxia inducible factor 2 (HIF-2) increased expression in punctured groups. Additionally, compare to adjacent non-punctured segments, HIF-2alpha expression level transiently increased and then decreased in the nucleus pulposus immediately following puncture, and it then increased 12weeks after puncture. SIGNIFICANCE: The degenerative changes observed in this rat-tail puncture model are similar to human disc degeneration and that this model may be valuable for elucidating the molecular mechanisms and pathways underlying disc degeneration. PMID- 27197028 TI - Lycopene ameliorates neuropathic pain by upregulating spinal astrocytic connexin 43 expression. AB - AIM: Peripheral nerve injury upregulates tumor necrosis factor (TNF) expression. In turn, connexin 43 (Cx43) expression in spinal astrocytes is downregulated by TNF. Therefore, restoration of spinal astrocyte Cx43 expression to normal level could lead to the reduction of nerve injury-induced pain. While the non provitaminic carotenoid lycopene reverses thermal hyperalgesia in mice with painful diabetic neuropathy, the antinociceptive mechanism is not entirely clear. The current study evaluated whether the antinociceptive effect of lycopene is mediated through the modulation of Cx43 expression in spinal astrocytes. MAIN METHODS: The effect of lycopene on Cx43 expression was examined in cultured rat spinal astrocytes. The effect of intrathecal lycopene on Cx43 expression and neuropathic pain were evaluated in mice with partial sciatic nerve ligation (PSNL). KEY FINDINGS: Treatment of cultured rat spinal astrocytes with lycopene reversed TNF-induced downregulation of Cx43 protein expression through a transcription-independent mechanism. By contrast, treatment of cultured spinal astrocytes with either pro-vitamin A carotenoid beta-carotene or antioxidant N acetyl cysteine had no effect on TNF-induced downregulation of Cx43 protein expression. In addition, repeated, but not single, intrathecal treatment with lycopene of mice with a partial sciatic nerve ligation significantly prevented not only the downregulation of Cx43 expression in spinal dorsal horn but mechanical hypersensitivity as well. SIGNIFICANCE: The current findings suggest a significant spinal mechanism that mediates the analgesic effect of lycopene, through the restoration of normal spinal Cx43 expression. PMID- 27197029 TI - Updates to instrumentation and protocols for isotopic analysis of nitrate by the denitrifier method. AB - RATIONALE: The denitrifier method allows for highly sensitive measurement of the (15) N/(14) N (delta(15) N value) and (18) O/(16) O (delta(18) O value) of nitrate dissolved in natural waters and for highly sensitive delta(15) N measurement of other N forms (e.g., organic N) that can be converted into nitrate. Here, updates to instrumentation and protocols are described, and improvements in data quality are demonstrated. METHODS: A 'heart cut' of the N2 O was implemented in the extraction system to (1) minimize introduction of contaminants into the mass spectrometer, reducing isotopic drift and (2) decrease the fraction of sample lost at the open split to improve sensitivity. Referencing protocols were updated, including a correction scheme for a weak dependence of nitrate delta(18) O values on nitrate concentration. Analyses of samples from the US GEOTRACES North Atlantic Program and of reference solutions from the same analysis batches were used to characterize performance. RESULTS: The drift is typically <0.10/00 for both delta(15) N and delta(18) O values. Within-batch and inter-batch replication yields 1 standard deviation (SD) of <=0.060/00 for delta(15) N values and <=0.140/00 for delta(18) O values down to 5 MUM nitrate and <=0.080/00 and <=0.230/00 at 2 and 1 MUM. The blank is typically 0.06 nmol N, 0.3% of the N in a 20 nmol N sample. Differences between reference materials in seawater are indistinguishable from reported differences for delta(15) N values, with a contraction for delta(18) O values of <=5%. CONCLUSIONS: The new instrumentation and protocols yield nitrate isotopic data with external precision of <=0.10/00 for large sample sets such as those derived from oceanographic sections. Further study should investigate the causes of (1) the weak dependence of nitrate delta(18) O values on nitrate concentration and (2) the inter-batch variation in the delta(18) O contraction (due mostly to oxygen atom exchange with water). Nevertheless, comprehensive correction schemes are in place for the measurement of both the delta(15) N and delta(18) O values of nitrate. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27197030 TI - Mass spectrometric determination of Morse parameters for the fifty-four superoxide states dissociating to the lowest limit. AB - RATIONALE: Superoxide is the most significant homonuclear diatomic anion in biochemistry. Theory predicts 12 doublet (X, A-K) and 12 quartet (a-l) electronic states split by spin orbital coupling into 54 states dissociating to the (3) P(O) + (2) P(O(-) ) limit. Dissociation energies for the 27 bonding states with positive electron affinities have been determined from mass spectrometric data. However, the 27 antibonding states with negative electron affinities have not been experimentally characterized. METHODS: The electron affinity of the hydrogen atom per electron, the Hylleraas, is the fundamental measure of electron correlation. It has been used to assign and evaluate experimental electron affinities of atoms and diatomic molecules. The 27 negative electron affinities of oxygen are estimated from the 27 positive values and the Hylleraas. These values are used to determine frequencies and internuclear separations by fitting theoretical electron impact distributions to the gas-phase mass spectrometric atomic oxygen anion distribution peaking at about 6.5 eV. RESULTS: The dissociation energies, internuclear distances and frequencies giving the first complete set of Morse potential energy curves for the 54 superoxide states dissociating to the lowest limit are reported from mass spectrometric data. The potentials are compared to theoretical and empirical literature curves. CONCLUSIONS: The existence of the 27 bonding and 27 antibonding spin orbital coupling superoxide states dissociating to (3) P(O) + (2) P(O(-) ) is established from mass analyzed thermal, photon, and electron ionization data. There are electron affinities from 0 to 0.15 eV, and onsets and peaks for dissociative electron attachment that cannot be explained by the 54 states. These support the existence of the 36 superoxide spin states dissociating to [(1) D(O) + (2) P(O(-) )] and [(1) S(O) + (2) P(O(-) )] predicted by quantum mechanics. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27197031 TI - Mass measurement accuracy of the Orbitrap in intact proteome analysis. AB - RATIONALE: The mass measurement accuracy (MMA) of Orbitrap mass spectrometers is 1-5 ppm according to the manufacturer's specification; yet, up to 50 ppm has been used as mass tolerance to interpret Orbitrap data in the literature. A systematic evaluation of MMA is thus necessary to find the optimal mass tolerance to be used. METHODS: Reversed-phase liquid chromatography/tandem mass spectrometry (RPLC/MS/MS) analyses of the intact E. coli proteome were carried out on a Q Exactive Orbitrap mass spectrometer coupled to a Dionex UltiMate 3000 RSLCnano system. The analysis included three technical replicates each day and was repeated for six continuous days right after a mass calibration. The obtained raw datasets were searched using ProteinGoggle 2.0 under four different mass tolerances of 5, 10, 15, and 20 ppm. RESULTS: With both forward and random database searches and FDR <=1% at the spectrum level, the most protein spectrum matches and protein IDs were obtained at a mass tolerance of 15 ppm. The average mass accuracy of both precursor and product ions from three representative high, medium, and low abundance proteins as well as the common proteins identified in all the 18 replicate runs was found to be 0-4 ppm; and no significant drift of measured mass accuracy was observed within the calibration period of 1 week. CONCLUSIONS: Despite the mass measurement accuracy of 1-5 ppm of the Orbitrap stated by the manufacturer, the optimal mass tolerance for protein identification was found to be 15 ppm for both the precursor and product ions. Weekly mass calibration is appropriate because no significant drift in MMA was found within the 6-day period. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27197032 TI - Laser-assisted proteolysis for accelerating and enhancing protein N-termini analysis. AB - RATIONALE: Targeted analysis of protein N-termini contributes to elucidating the starting sites and post-translational modifications of mature protein N-termini. Tryptic digestion is important in protein N-termini analysis, as well as in conventional bottom-up proteomics strategies. It is essential to explore a new proteolysis method for the enhancement of protein N-termini analysis. METHODS: Laser-assisted proteolysis was compared with conventional overnight proteolysis. Four standard proteins were studied as models and analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. 100 pg of synthesized peptide was used as internal standard for comparison of N-terminus intensity. Laser-assisted proteolysis was demonstrated to accelerate and enhance N-termini analysis. A complex mouse liver proteome sample was used to validate the effect of laser-assisted proteolysis. RESULTS: According to online database search, the number of matched peptides of four model proteins and the sequence coverage were comparable between the two proteolysis methods. Laser exposure time (40 s) could enhance the release of the N-terminus in model proteins. The number of identified N-termini in mouse liver was improved by 28.3% in the laser assisted digest, compared to the conventional overnight digest. The time cost for digestion was shortened from overnight to 40 s. CONCLUSIONS: Laser-assisted proteolysis was demonstrated to accelerate proteolysis and enhance N-termini analysis. If laser-assisted proteolysis was integrated into protein N-termini targeted methods, the performance of those methods should be improved. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27197033 TI - Effect of surface capping of quantum dots (CdTe) on proteomics. AB - RATIONALE: Investigation of nanoparticles for laser desorption/ionization mass spectrometry (LDI-MS) is routinely reported. However, the effect of surface capping of nanomaterials for LDI-MS is not well studied. METHODS: Different capping agents of quantum dots (CdTe) affect the spectra quality and sensitivity of protein analysis and protein digestion using trypsin enzyme assisted by microwave. Surface modification of CdTe quantum dots with different capping agents, namely 3-mercaptopropionic acid (3-MPA), 4-aminothiophenol (4-ATP), 4 mercaptobenzoic acid (4-MBA), 11-mercaptoundecanoic acid (11-MUA), cysteine (Cys) and thioglycolic acid (TG), were investigated for quantum dots (QDs)-assisted trypsin protease followed by analysis using mass spectrometry. RESULTS: CdTe QDs were used as a surface to assist trypsin protease and laser desorption/ionization mass spectrometry (surface-assisted laser desorption/ionization mass spectrometry, SALDI-MS). The MS profiles for the investigated analytes (bovine serum albumin (BSA), lysozyme, cytochrome c, alpha-casein, transferrin and myoglobin) revealed almost the absence of degradation that implies the softness of the present technique. QDs-assisted LDI-MS offered high sensitivity and high resolution. QDs showed significant enhancement of microwave-assisted trypsin digestion of the investigated proteins and these improvements boosted the identifications of fragments with a database. CONCLUSIONS: A capping agent of quantum dots affects the analysis of proteins and peptides using LDI-MS. CdTe QDs offer sensitive, high-resolution and simple analysis of proteins. QDs improved the protein digestion using the microwave-assisted trypsin digestion. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27197034 TI - Mass spectrometric evaluation of neurotransmitter levels in IMR 32 cell line in response to Ayurvedic medicines. AB - RATIONALE: Ayurvedic herbal medicines are administered as part of disease management for many neurodevelopmental disorders like Autism Spectrum Disorder (ASD) and linked comorbid challenges. The biochemistry of the behavioral abnormalities as observed in comorbid conditions is already reported to involve neurotransmitters like gamma-aminobutyric acid (GABA), serotonin (5-HT) and dopamine (DA). The aim of our study is to evaluate the effect of ayurvedic medicines on neurotransmitter levels in IMR 32. Such a study will give some insight into the molecular mechanism of the action of these medicines and help us to understand their contributions in neurotransmitter homeostasis. METHODS: Solutions of Brahmi, Brahmi vati, Brahmi ghrita and Saraswata ghrita, each at 50 MUM, were added to differentiated IMR 32 cells and grown for 24 h. The cell secretion was analysed by ultra-fast liquid chromatography/mass spectrometry (UFLC/MS) in electrospray ionisation (ESI) mode for the neurotransmitters DA, 5 HT and GABA. The mobile phase selected was 0.1% formic acid with 15 MUg/mL Na2 EDTA (A) and 0.1% formic acid in acetonitrile (B) introduced in the ratio of 92:8. RESULTS: All neurotransmitters under study were eluted within 7 min with GABA eluting at 3.82 min, 5-HT at 4.48 min and DA at 5.47 min, respectively. Linearity was excellent with a correlation coefficient (R(2) ) of 0.999; repeatability and accuracy were also within acceptable range. All herbal drugs evaluated increased the neurotransmitter levels and Brahmi vati increased the neurotransmitter levels to a larger extent. CONCLUSIONS: Decreased levels of neurotransmitters were observed in behavioral abnormalities which were also observed in children with ASD. Herbal medicines given as part of ayurvedic medicine increased the neurotransmitter levels in IMR 32. Thus, these ayurvedic medicines when prescribed to children with ASD might alleviate the abnormal behavioral symptoms by maintaining neurotransmitter homeostasis. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27197035 TI - Geographical variability in northern European sheep wool isotopic composition (delta(13) C, delta(15) N, delta(2) H values). AB - RATIONALE: Light stable isotopic analysis of herbivore proteinaceous tissues (hair, muscle, milk) is critical for authenticating the point of origin of finished agricultural or industrial products in both ancient and modern economies. This study examined the distribution of light stable isotopes in herbivores in northern Europe (Iceland to Finland), which is expected to depend on regional-level environmental inputs (precipitation, temperature) and local variables (vegetation type, fodder type, soil type). METHODS: Sheep wool was obtained from animals managed using traditional methods and located across a gradient of northern European environments. Defatted whole-year samples were analysed by isotope ratio mass spectrometry (IRMS) for carbon (delta(13) C values), nitrogen (delta(15) N values) and un-exchangeable hydrogen (delta(2) H values) isotopic composition. RESULTS: Wool delta(13) C, delta(15) N and delta(2) H values showed the same correlations to local mean annual precipitation and temperature as were expected for graze plants. Wool delta(2) H values were correlated with local modelled meteoric water delta(2) H values, mediated by plant solid tissue and leaf water fractionations. Cluster analysis distinguished wool from Sweden and the Baltic region from more western material. Local variation in vegetation or soil type did not disrupt dependence on climatic variables but did affect geospatial discrimination. CONCLUSIONS: Wool isotopic composition in northern Europe is controlled by the effects of local precipitation and temperature on graze plant inputs, and is only weakly affected by pasture type. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27197036 TI - Gas-phase ion-molecule reactions for the identification of the sulfone functionality in protonated analytes in a linear quadrupole ion trap mass spectrometer. AB - RATIONALE: The oxidation of sulfur atoms is an important biotransformation pathway for many sulfur-containing drugs. In order to rapidly identify the sulfone functionality in drug metabolites, a tandem mass spectrometric method based on ion-molecule reactions was developed. METHODS: A phosphorus-containing reagent, trimethyl phosphite (TMP), was allowed to react with protonated analytes with various functionalities in a linear quadrupole ion trap mass spectrometer. The reaction products and reaction efficiencies were measured. RESULTS: Only protonated sulfone model compounds were found to react with TMP to form a characteristic [TMP adduct-MeOH] product ion. All other protonated compounds investigated, with functionalities such as sulfoxide, N-oxide, hydroxylamino, keto, carboxylic acid, and aliphatic and aromatic amino, only react with TMP via proton transfer and/or addition. The specificity of the reaction was further demonstrated by using a sulfoxide-containing anti-inflammatory drug, sulindac, as well as its metabolite sulindac sulfone. CONCLUSIONS: A method based on functional group-selective ion-molecule reactions in a linear quadrupole ion trap mass spectrometer has been demonstrated for the identification of the sulfone functionality in protonated analytes. A characteristic [TMP adduct-MeOH] product ion was only formed for the protonated sulfone analytes. The applicability of the TMP reagent in identifying sulfone functionalities in drug metabolites was also demonstrated. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27197037 TI - Intimacy after prostate cancer: A brief couples' workshop is associated with improvements in relationship satisfaction. AB - OBJECTIVE: Prostate cancer (PCa) treatments often leave men with erectile dysfunction (ED). Even when ED treatments are effective in restoring men's ability to have an erection sufficient for intercourse, couples continue to struggle sexually. Effective treatments to help couples recover sexually are needed. METHOD: PCa patients and partners (N = 59 couples) attending a one-time couples' intimacy workshop, participated in an evaluation. The workshop, offered eight times over a 2-year period, emphasized a couples-based approach to treatment that enhances direct communication about sexuality and implementation of sexual recovery strategies that are consistent with the couple's values. Couples completed pre and post questionnaires (at baseline and 2 months later) assessing the primary outcome of relationship adjustment (Revised Dyadic Adjustment Scale) and secondary outcome of sexual function (Sexual Function Questionnaire). T-tests were employed to examine pre-post changes in scores. A small qualitative sub-study was conducted on the use of a Commitment to Change goal-setting exercise, completed during the workshop. RESULTS: Results provide insight into the specific nature of improvements. Patients and partners showed improvements in relationship satisfaction. Improvements with small-to-medium effect sizes were observed for patients and partners sexual function; however, after adjusting for multiple comparisons, these changes were no longer statistically significant. The specific goals set by couples, and their achievement status, are presented. CONCLUSIONS: The workshop offers a comprehensive, one-session intervention to help couples implement a treatment plan to promote sexual recovery after PCa treatment. Given the observed improvements, progression to a randomized control trial is warranted. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27197038 TI - Right-Sided Laryngeal Mass With Hoarseness. PMID- 27197044 TI - Do We Know Whether Researchers and Reviewers are Estimating Risk and Benefit Accurately? AB - Accurate estimation of risk and benefit is integral to good clinical research planning, ethical review, and study implementation. Some commentators have argued that various actors in clinical research systems are prone to biased or arbitrary risk/benefit estimation. In this commentary, we suggest the evidence supporting such claims is very limited. Most prior work has imputed risk/benefit beliefs based on past behavior or goals, rather than directly measuring them. We describe an approach - forecast analysis - that would enable direct and effective measure of the quality of risk/benefit estimation. We then consider some objections and limitations to the forecasting approach. PMID- 27197039 TI - Volcanic air pollution over the Island of Hawai'i: Emissions, dispersal, and composition. Association with respiratory symptoms and lung function in Hawai'i Island school children. AB - BACKGROUND: Kilauea Volcano on the Island of Hawai'i has erupted continuously since 1983, releasing approximately 300-12000metrictons per day of sulfur dioxide (SO2). SO2 interacts with water vapor to produce an acidic haze known locally as "vog". The combination of wind speed and direction, inversion layer height, and local terrain lead to heterogeneous and variable distribution of vog over the island, allowing study of respiratory effects associated with chronic vog exposure. OBJECTIVES: We characterized the distribution and composition of vog over the Island of Hawai'i, and tested the hypotheses that chronic vog exposure (SO2 and acid) is associated with increased asthma prevalence, respiratory symptoms, and reduced pulmonary function in Hawai'i Island schoolchildren. METHODS: We compiled data of volcanic emissions, wind speed, and wind direction over Hawai'i Island since 1992. Community-based researchers then measured 2- to 4 week integrated concentrations of SO2 and fine particulate mass and acidity in 4 exposure zones, from 2002 to 2005, when volcanic SO2 emissions averaged 1600metrictons per day. Concurrently, community researchers recruited schoolchildren in the 4th and 5th grades of 25 schools in the 4 vog exposure zones, to assess determinants of lung health, respiratory symptoms, and asthma prevalence. RESULTS: Environmental data suggested 4 different vog exposure zones with SO2, PM2.5, and particulate acid concentrations (mean+/-s.d.) as follows: 1) Low (0.3+/-0.2ppb, 2.5+/-1.2MUg/m(3), 0.6+/-1.1nmolH+/m(3)), 2) Intermittent (1.6+/-1.8ppb, 2.8+/-1.5MUg/m(3), 4.0+/-6.6nmolH+/m(3)), 3) Frequent (10.1+/ 5.2ppb, 4.8+/-1.9MUg/m(3), 4.3+/-6.7nmolH+/m(3)), and 4) Acid (1.2+/-0.4ppb, 7.2+/-2.3MUg/m(3), 25.3+/-17.9nmolH+/m(3)). Participants (1957) in the 4 zones differed in race, prematurity, maternal smoking during pregnancy, environmental tobacco smoke exposure, presence of mold in the home, and physician-diagnosed asthma. Multivariable analysis showed an association between Acid vog exposure and cough and strongly suggested an association with FEV1/FVC <0.8, but not with diagnosis of asthma, or chronic persistent wheeze or bronchitis in the last 12months. CONCLUSIONS: Hawai'i Island's volcanic air pollution can be very acidic, but contains few co-contaminants originating from anthropogenic sources of air pollution. Chronic exposure to acid vog is associated with increased cough and possibly with reduced FEV1/FVC, but not with asthma or bronchitis. Further study is needed to better understand how volcanic air pollution interacts with host and environmental factors to affect respiratory symptoms, lung function, and lung growth, and to determine acute effects of episodes of increased emissions. PMID- 27197046 TI - QuickStats: Age-Adjusted Suicide Rates* for Females and Males, by Method(?) - National Vital Statistics System, United States, 2000 and 2014. AB - From 2000 to 2014, the age-adjusted suicide rate increased from 4.0 to 5.8 per 100,000 for females and from 17.7 to 20.7 for males. Suicide rates by specific method (firearm, poisoning, suffocation, or other methods) also increased, with the greatest increase seen for suicides by suffocation. During the 15-year period, the rate of suicide by suffocation more than doubled for females from 0.7 to 1.6 and increased from 3.4 to 5.6 for males. In 2014, among females, suicide by poisoning had the highest rate (1.9), and among males, suicide by firearm had the highest rate (11.4). PMID- 27197047 TI - Influence of a 6-h interruption of agitation on in vitro properties of volume reduced washed platelets in M-sol additive solution. PMID- 27197045 TI - Surface modification of nanoparticles enables selective evasion of phagocytic clearance by distinct macrophage phenotypes. AB - Nanomedicine is a burgeoning industry but an understanding of the interaction of nanomaterials with the immune system is critical for clinical translation. Macrophages play a fundamental role in the immune system by engulfing foreign particulates such as nanoparticles. When activated, macrophages form distinct phenotypic populations with unique immune functions, however the mechanism by which these polarized macrophages react to nanoparticles is unclear. Furthermore, strategies to selectively evade activated macrophage subpopulations are lacking. Here we demonstrate that stimulated macrophages possess higher phagocytic activities and that classically activated (M1) macrophages exhibit greater phagocytic capacity than alternatively activated (M2) macrophages. We show that modification of nanoparticles with polyethylene-glycol results in decreased clearance by all macrophage phenotypes, but importantly, coating nanoparticles with CD47 preferentially lowers phagocytic activity by the M1 phenotype. These results suggest that bio-inspired nanoparticle surface design may enable evasion of specific components of the immune system and provide a rational approach for developing immune tolerant nanomedicines. PMID- 27197048 TI - Changes in Childhood Pneumonia Hospitalizations by Race and Sex Associated with Pneumococcal Conjugate Vaccines. AB - Introduction of pneumococcal conjugate vaccines in the childhood immunization schedule was associated with decreases in all-cause pneumonia hospitalizations among black and white children in Tennessee, USA. Although racial disparities that existed before introduction of these vaccines have been substantially reduced, rates remain higher in boys than in girls among young children. PMID- 27197049 TI - Protonation induces base rotation of purine nucleotides pdGuo and pGuo. AB - Infrared multiple photon dissociation (IRMPD) action spectra of the protonated forms of 2'-deoxyguanosine-5'-monophosphate and guanosine-5'-monophosphate, [pdGuo+H](+) and [pGuo+H](+), are measured over the IR fingerprint and hydrogen stretching regions using the FELIX free electron laser and an OPO/OPA laser system. Electronic structure calculations are performed to generate low-energy conformations of [pdGuo+H](+) and [pGuo+H](+) and determine their relative stabilities at the B3LYP/6-311+G(2d,2p)//B3LYP/6-311+G(d,p) and MP2(full)/6 311+G(2d,2p)//B3LYP/6-311+G(d,p) levels of theory. Comparative analyses of the measured IRMPD action spectra and B3LYP/6-311+G(d,p) linear IR spectra computed for the low-energy conformers are performed to determine the most favorable site of protonation and the conformers present in the experiments. These comparisons and the computed energetics find that N7 protonation is considerably preferred over O6 and N3, and the N7 protonated ground-state conformers of [pdGuo+H](+) and [pGuo+H](+) are populated in the experiments. The 2'-hydroxyl substituent does not significantly impact the stable low-energy conformers of [pdGuo+H](+)vs. those of [pGuo+H](+). The effect of the 2'-hydroxyl substituent is primarily reflected in the relative intensities of the measured IRMPD bands, as the IRMPD profiles of [pdGuo+H](+) and [pGuo+H](+) are quite similar. Comparisons to previous IRMPD spectroscopy investigations of the protonated forms of the guanine nucleosides, [dGuo+H](+) and [Guo+H](+), and deprotonated forms of the guanine nucleotides, [pdGuo-H](-) and [pGuo-H](-), provide insight into the effects of the phosphate moiety and protonation on the conformational features of the nucleobase and sugar moieties. Protonation is found to induce base rotation of the guanine residue to an anti orientation vs. the syn orientation found for the deprotonated forms of the guanine nucleotides. PMID- 27197050 TI - The Impact of Inappropriate Implantable Cardiac Defibrillator Shocks on Cardiovascular Morbidity and Mortality. AB - BACKGROUND: The impact of inappropriate implantable cardiac defibrillator (ICD) shocks on cardiac outcomes is controversial. Shocks due to lead noise are unique in that they are not an outcome of worsening rhythm status. In this study, we compared the outcome of patients with and without inappropriate shocks who underwent Sprint Fidelis lead (Medtronic Inc., Minneapolis, MN, USA) extraction. METHODS: We retrospectively identified 147 patients who underwent Sprint Fidelis lead extraction in our institution between May 2007 and August 2012. The patients were separated into those with (Group 1) and without (Group 2) inappropriate shocks due to lead noise. Pertinent data were obtained from chart review. RESULTS: There were 57 and 90 patients in Groups 1 and 2, respectively. The mean +/- standard deviation number of inappropriate shocks in Group 1 was 16 +/- 22. There was no difference in the baseline demographics, risk factors, and cardiac history between the groups. There were no extraction-related deaths and there was no difference in the rate of periprocedural complications between the groups. The mean total hospital length of stay (LOS) was longer for Group 1 versus 2; however, the mean postprocedure LOS was the same between the groups. During follow-up, there was no difference in the cardiac readmission rate over a 1-year period (four vs seven patients in Group 1 vs 2, respectively; P = 0.8). Long-term follow-up revealed similar mortality rates in both groups. (18 patients in Group 1, and 21 patients in Group 2; P = 0.8). CONCLUSIONS: Inappropriate shocks due to lead noise do not seem to predispose to a worse clinical outcome after ICD lead extraction. PMID- 27197051 TI - Statin-induced liver injury in an area endemic for hepatitis B virus infection: risk factors and outcome analysis. AB - AIMS: Statin-induced liver injury (SILI) is quite rare, but may be severe. Little is known about the impact of chronic hepatitis B infection (CHBI) on SILI. We aimed to investigate the risk factors and outcome of SILI, with special reference to its interaction with CHBI. METHODS: Patients with SILI were recruited from our hospital, and three-to-one drug-matched controls were randomly selected. The clinical data of the patients were then compared. RESULTS: A total of 108 patients with SILI and 324 controls were enrolled. The patients with SILI were both older and had a higher statin dose than the controls. There was no predilection of liver injury associated with the seven available statins. Among the SILI patients, there was no statistical difference between the baseline and peak liver enzyme tests, and latency and severity between hepatitis B carriers (n = 16) and non-carriers (n = 92). High dose of statin and age were the two independent risk factors of SILI (OR and 95% CI: 1.93, 1.08-3.35, P = 0.025, and 1.73, 1.07-2.80, P = 0.027, respectively). Permanent discontinuation of statin was noted in 50 (46.3%) patients with SILI due to severe SILI or recurrent hepatotoxicity after rechallenge of other statins. CONCLUSION: High dose of statin and old age may increase patient susceptibility to SILI; however, CHBI and abnormal baseline liver tests are not risk factors of SILI. Nonetheless, SILI is still worthy of notice, because nearly half of the overt cases discontinued statin treatment due to severe hepatotoxicity in this study. PMID- 27197052 TI - Phylogenetic and functional analysis of sequence variation of human papillomavirus type 31 E6 and E7 oncoproteins. AB - High-risk human papillomaviruses (HPV) are the causative agents of cervical and other anogenital cancers as well as a subset of head and neck cancers. The E6 and E7 oncoproteins of HPV contribute to oncogenesis by associating with the tumour suppressor protein p53 and pRb, respectively. For HPV types 16 and 18, intratypic sequence variation was shown to have biological and clinical significance. The functional significance of sequence variation among HPV 31 variants was studied less intensively. HPV 31 variants belonging to different variant lineages were found to have differences in persistence and in the ability to cause high grade cervical intraepithelial neoplasia. In the present study, we started to explore the functional effects of natural sequence variation of HPV 31 E6 and E7 oncoproteins. The E6 variants were tested for their effects on p53 protein stability and transcriptional activity, while the E7 variants were tested for their effects on pRb protein level and also on the transcriptional activity of E2F transcription factors. HPV 31 E7 variants displayed uniform effects on pRb stability and also on the activity of E2F transcription factors. HPV 31 E6 variants had remarkable differences in the ability to inhibit the trans activation function of p53 but not in the ability to induce the in vivo degradation of p53. Our results indicate that natural sequence variation of the HPV 31 E6 protein may be involved in the observed differences in the oncogenic potential between HPV 31 variants. PMID- 27197054 TI - Predicting pupylation sites in prokaryotic proteins using semi-supervised self training support vector machine algorithm. AB - As one important post-translational modification of prokaryotic proteins, pupylation plays a key role in regulating various biological processes. The accurate identification of pupylation sites is crucial for understanding the underlying mechanisms of pupylation. Although several computational methods have been developed for the identification of pupylation sites, the prediction accuracy of them is still unsatisfactory. Here, a novel bioinformatics tool named IMP-PUP is proposed to improve the prediction of pupylation sites. IMP-PUP is constructed on the composition of k-spaced amino acid pairs and trained with a modified semi-supervised self-training support vector machine (SVM) algorithm. The proposed algorithm iteratively trains a series of support vector machine classifiers on both annotated and non-annotated pupylated proteins. Computational results show that IMP-PUP achieves the area under receiver operating characteristic curves of 0.91, 0.73, and 0.75 on our training set, Tung's testing set, and our testing set, respectively, which are better than those of the different error costs SVM algorithm and the original self-training SVM algorithm. Independent tests also show that IMP-PUP significantly outperforms three other existing pupylation site predictors: GPS-PUP, iPUP, and pbPUP. Therefore, IMP-PUP can be a useful tool for accurate prediction of pupylation sites. A MATLAB software package for IMP-PUP is available at https://juzhe1120.github.io/. PMID- 27197055 TI - Higher Gemcitabine Dose Was Associated With Better Outcome of Osteosarcoma Patients Receiving Gemcitabine-Docetaxel Chemotherapy. AB - BACKGROUND: Efficacy of gemcitabine and docetaxel (GEM + DOC) chemotherapy in patients with recurrent or refractory osteosarcoma was evaluated. METHODS: Data of 53 patients from 9 institutions, who received GEM (675 or 900 mg/m(2) on days 1 and 8) and DOC (100 mg/m(2) on day 8), were retrospectively reviewed. RESULTS: GEM + DOC was administered as adjuvant (n = 25) or palliative chemotherapy (n = 28). Patients received a median 3 courses (range, 1-10 courses). Objective response rate (CR + PR, where CR is complete response and PR is partial response) and disease control rate (CR+ PR + SD, where SD is stable disease) were 14.3% and 28.6%, respectively. Disease control rate was higher in patients receiving 900 mg/m(2) GEM than in patients receiving 675 mg/m(2) (50.0% vs. 12.5%, P = 0.03). Higher GEM dose was associated with better survival, both in adjuvant (1-year overall survival, 90.9 +/- 8.7% vs. 38.5 +/- 13.5%, P = 0.002) and palliative settings (50.0 +/- 14.4% vs. 31.3 +/- 11.6%, P = 0.04). CONCLUSIONS: Further studies are necessary to investigate the efficacy of more aggressive and higher doses of GEM + DOC chemotherapy in osteosarcoma. PMID- 27197056 TI - Capecitabine and lapatinib for the first-line treatment of metastatic/recurrent head and neck squamous cell carcinoma. AB - BACKGROUND: The combination of cisplatin, 5-fluorouracil, and cetuximab is a standard treatment for patients with recurrent/metastatic head and neck cancer, with a high rate of toxicity. Identifying less toxic, equally effective regimens is imperative. Therefore, in the current study, the authors investigated first line treatment with an all-oral regimen of capecitabine and lapatinib. METHODS: Patients were required to have incurable head and neck cancer of any primary site other than the nasopharynx, an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 2, and no prior exposure to capecitabine or lapatinib. Subjects were treated with capecitabine at a dose of 1000 mg/m(2) twice daily and lapatinib at a dose of 1250 mg daily. Capecitabine was administered for 14 days of each 21-day cycle for 4 cycles. Lapatinib was administered daily until disease progression. The primary outcome was overall survival. RESULTS: A total of 44 subjects were accrued between November 13, 2009 and April 29, 2014. Approximately 38.6% of the sample had an ECOG PS of 0, 52.3% had an ECOG PS of 1, and 9.1% had an ECOG PS of 2. Approximately 81.8% were male and the median age of the patients was 62 years. Prior attempts at curative treatment with chemotherapy had been used in 68.2% of patients (platinum was used in 55.8%). There was no grade 5 toxicity noted (toxicity was graded according to National Cancer Institute Common Terminology Criteria for Adverse Events [version 3.0]). The most common adverse events were diarrhea (18.2% of patients with grade 3) and rash (13.6% of patients with grade 3). The primary objective was met; the median overall survival was 10.7 months (90% confidence interval [90% CI], 8.7-12.9 months). The overall response rate was 25% (90% CI, 15%-38%). The median progression-free survival was 4.2 months (90% CI, 3.6-5.1 months). The results were not substantially different when subdivided by p16 status. Only 2 patients were positive for human epidermal growth factor receptor 2 by immunohistochemistry. CONCLUSIONS: The current study met its primary objective of survival comparable to the combination of cisplatin, 5-FU and cetuximab regimen, and the toxicity of this all-oral regimen was tolerable. Cancer 2016;122:2350-2355. (c) 2016 American Cancer Society. PMID- 27197057 TI - Applying the Critical Speed Concept to Racing Strategy and Interval Training Prescription. AB - The use of personal records (PRs) for running different distances may be used to derive critical speed (CS) and the finite capacity for running speeds exceeding CS (D'). Using CS and D', individualized speed-time and distance-time relationships can be modeled (ie, time limits associated with running at a given speed or a given distance can be derived via linear regression with a high degree of accuracy). The running 3-min all-out exercise test (3 MT) has emerged as a method for estimating CS and D' on a large group of athletes in a single visit. Such a procedure is useful when PRs are not readily available (eg, team-sport athletes). This article reviews how to administer and interpret the running 3 MT, how CS and D' can inform racing strategy, and how CS and D' can be used to prescribe and evaluate high-intensity interval training (HIIT). Directions for deriving HIIT bouts using either fixed distances or fixed speeds are provided along with CS dose-responses to short-term HIIT programs. PMID- 27197058 TI - Electromembrane extraction of tartrazine from food samples: Effects of nano sorbents on membrane performance. AB - In the present study, for the first time electromembrane extraction followed by high-performance liquid chromatography coupled with ultraviolet detection was developed and validated for the determination of tartrazine in some food samples. The parameters influencing electromembrane extraction were evaluated and optimized. The membrane consists of 1-octanol immobilized in the pores of a hollow fiber. As a driving force, a 30 V electrical field was applied to make the analyte migrate from sample solution with pH 3, through the supported liquid membrane into an acceptor solution with pH 10. Best preconcentration (enrichment factor >21) was obtained in extraction duration of 15 min. Effects of some solid nano-sorbents like carbon nanotubes and molecularly imprinted polymers on membrane performance and electromembrane extraction efficiency were evaluated. The method provided the linearity in the range 25-1000 ng/mL for tartrazine (R(2) > 0.9996) with repeatability range (RSD) between 3.8 and 8.5% (n = 3). The limits of detection and quantitation were 7.5 and 25 ng/mL, respectively. Finally, the method was applied to the determination and quantification of tartrazine from some food samples with relative recoveries in the range between 90 and 98%. PMID- 27197053 TI - The role of evolutionary biology in research and control of liver flukes in Southeast Asia. AB - Stimulated largely by the availability of new technology, biomedical research at the molecular-level and chemical-based control approaches arguably dominate the field of infectious diseases. Along with this, the proximate view of disease etiology predominates to the exclusion of the ultimate, evolutionary biology based, causation perspective. Yet, historically and up to today, research in evolutionary biology has provided much of the foundation for understanding the mechanisms underlying disease transmission dynamics, virulence, and the design of effective integrated control strategies. Here we review the state of knowledge regarding the biology of Asian liver Fluke-host relationship, parasitology, phylodynamics, drug-based interventions and liver Fluke-related cancer etiology from an evolutionary biology perspective. We consider how evolutionary principles, mechanisms and research methods could help refine our understanding of clinical disease associated with infection by Liver Flukes as well as their transmission dynamics. We identify a series of questions for an evolutionary biology research agenda for the liver Fluke that should contribute to an increased understanding of liver Fluke-associated diseases. Finally, we describe an integrative evolutionary medicine approach to liver Fluke prevention and control highlighting the need to better contextualize interventions within a broader human health and sustainable development framework. PMID- 27197059 TI - Tumor reactive ringlet oxygen approach for Monte Carlo modeling of photodynamic therapy dosimetry. AB - Photodynamic therapy (PDT) is an emergent technique used for the treatment of several diseases. It requires the interaction of three components: a photosensitizer, a light source and tissue oxygen. Knowledge of the biophysical aspects of PDT is important for improving dosimetry protocols and treatment planning. In this paper we propose a model to simulate the spatial and temporal distribution of ground state oxygen ((3)O2), cumulative singlet excited state oxygen ((1)O2)rx and photosensitizer, in this case protoporphyrin IX (PpIX) in an ALA mediated PDT treatment. The results are analyzed in order to improve the treatment dosimetry. We compute the light fluence in the tissue using Monte Carlo simulations running in a GPU system. The concentration of (3)O2, ((1)O2)rx and the photosensitizer are calculated using this light fluence and a set of differential equations describing the photochemical reactions involved in PDT. In the model the initial photosensitizer concentration depends on tissue depth and type, moreover we consider blood vessel damage and its effect in the ground state oxygen concentration in the tissue. We introduce the tumor reactive single oxygen (TRSO) as a new dosimetry metric. It represents the amount of singlet oxygen per tumor volume that reacts, during the treatment, with the molecules in the tumor. This quantity integrates the effect of the light irradiance, the optical properties of the tumor and the normal tissue, the oxygen consumption and supply, and the photosensitizer biodistribution on the skin. PMID- 27197060 TI - Synthesis, characterization, molecular docking and biological studies of self assembled transition metal dithiocarbamates of substituted pyrrole-2 carboxaldehyde. AB - A series of self assembled 3d transition metal dithiocarbamate, M(pdtc) [where M=Mn(II), Fe(II), Co(II), Ni(II) and Cu(II)] have been synthesized and spectroscopically characterized. The bidentate dithiocarbamate ligand Na2pdtc (Disodium-1,4-phenyldiaminobis (pyrrole-1-sulfino)dithioate) was prepared by insertion reaction of carbondisulfide with Schiff base, N,N'-bis-(1H-pyrrol-2 ylmethylene)-benzene-1,4-diamine (L1) in basic medium. The simple substitution reaction between the metal halide and Na2pdtc yielded the title complexes in moderate yields. However, the in situ procedure gives high yield with the formation of single product as evident by TLC. Elemental analysis, IR, (1)H and (13)C NMR spectra, UV-vis., magnetic susceptibility and conductance measurements were done to characterize the complexes, M(pdtc). All the evidences suggest that the complexes have tetrahedral geometry excepting Cu(II) which is found to be square planar. A symmetrical bidentate coordination of the dithiocarbamato moiety has been observed in all the complexes. The conductivity data show that the complexes are non-electrolyte in nature. The anti-oxidant activity of the ligand, Na2pdtc and its transition metal complexes, M(pdtc) have been carried out using DPPH and Cu(pdtc) was found to be most effective. The anti-microbial activity of the Na2pdtc and M(pdtc) complexes have been carried out and on this basis the molecular docking study of the most effective complex, Cu(pdtc) has also been reported. PMID- 27197061 TI - Pretreatment Immune Status Correlates with Progression-Free Survival in Chemotherapy-Treated Metastatic Colorectal Cancer Patients. AB - It remains unclear whether the immunologic status of cells in peripheral blood can be used as a prognostic indicator of response to treatment for patients with unresectable metastatic colorectal cancer (MCRC). We therefore investigated the relationship between the pretreatment immunologic status of 40 patients with MCRC who planned to receive the first-line chemotherapy and their progression-free survival. Twenty-five immune cell subsets, including monocytic myeloid-derived suppressor cells (M-MDSC) and effector memory T cells (TEM), were measured by multicolor-flow cytometry. We divided patients into high and low (above and below the median, respectively) groups based on the median value for each immune cell subset and compared progression-free survival of the two groups. Patients with high M-MDSC, low CD4(+) TEM, or low CD8(+) TEM quantities had significantly shorter progression-free survival (P = 0.004, 0.005, and 0.002, respectively). Patients were classified into two prognostic groups based on numbers of adverse factors; having two or three adverse factors (n = 21, 52.5%) was correlated with significantly shorter progression-free survival compared with none or one (n = 19, 47.5%; P < 0.001). The presence of two or three adverse factors was an independent poor prognostic factor for progression-free survival (HR, 9.2; 95% confidence interval, 2.5-34.2; P < 0.001). These results provide evidence that pretreatment peripheral immune status can inform the outcome of patients with MCRC treated with first-line chemotherapy. Cancer Immunol Res; 4(7); 592-9. (c)2016 AACR. PMID- 27197062 TI - Immune-Derived PD-L1 Gene Expression Defines a Subgroup of Stage II/III Colorectal Cancer Patients with Favorable Prognosis Who May Be Harmed by Adjuvant Chemotherapy. AB - A recent phase II study of patients with metastatic colorectal carcinoma showed that mismatch repair gene status was predictive of clinical response to PD-1 targeting immune checkpoint blockade. Further examination revealed strong correlation between PD-L1 protein expression and microsatellite instability (MSI) in stage IV colorectal carcinoma, suggesting that the amount of PD-L1 protein expression could identify late-stage patients who might benefit from immunotherapy. To assess whether the clinical associations between PD-L1 gene expression and MSI identified in metastatic colorectal carcinoma are also present in stage II/III colorectal carcinoma, we used in silico analysis to elucidate the cell types expressing the PD-L1 gene. We found a statistically significant association of PD-L1 gene expression with MSI in early-stage colorectal carcinoma (P < 0.001) and show that, unlike in non-colorectal carcinoma tumors, PD-L1 is derived predominantly from the immune infiltrate. We demonstrate that PD-L1 gene expression has positive prognostic value in the adjuvant disease setting (PD L1(low) vs. PD-L1(high) HR = 9.09; CI, 2.11-39.10). PD-L1 gene expression had predictive value, as patients with high PD-L1 expression appear to be harmed by standard-of-care treatment (HR = 4.95; CI, 1.10-22.35). Building on the promising results from the metastatic colorectal carcinoma PD-1-targeting trial, we provide compelling evidence that patients with PD-L1(high)/MSI/immune(high) stage II/III colorectal carcinoma should not receive standard chemotherapy. This conclusion supports the rationale to clinically evaluate this patient subgroup for PD-1 blockade treatment. Cancer Immunol Res; 4(7); 582-91. (c)2016 AACR. PMID- 27197063 TI - Prolonged Benefit from Ipilimumab Correlates with Improved Outcomes from Subsequent Pembrolizumab. AB - Patients with metastatic melanoma whose disease progresses on ipilimumab can clearly derive benefit from subsequent anti-programmed death-1 (PD-1). However, patients experience heterogeneous outcomes with ipilimumab, including rapid or delayed progression, and it is unclear whether patterns of ipilimumab progression influence subsequent clinical responses to anti-PD-1. We retrospectively reviewed data from 116 patients with metastatic melanoma who progressed on ipilimumab and were subsequently treated with pembrolizumab. The study objectives were to determine whether progression-free survival (PFS) with ipilimumab was associated with PFS, objective response rate (ORR), and clinical benefit rate (CBR; ORR + stable disease) with pembrolizumab. Patients with PFS >=90 days after treatment with ipilimumab generally had superior outcomes with subsequent pembrolizumab treatment compared with patients with PFS <90 days (ORR, 49% vs. 35%, P = 0.12; CBR, 66% vs. 46%, P = 0.03). Patients with prolonged ipilimumab benefit (PFS >= 180 days) had excellent outcomes with pembrolizumab compared with rapid progressors (PFS < 45 days; ORR, 55% vs. 25%; CBR, 80% vs. 25%; median PFS, 249 vs. 50 days). Using logistic regression models, PFS with ipilimumab was independently correlated with response to pembrolizumab (odds ratio, 1.22; 95% CI, 1.02-1.51). This study shows that prolonged PFS with ipilimumab predicts excellent outcomes with subsequent pembrolizumab treatment, offering valuable prognostic information for clinicians. Cancer Immunol Res; 4(7); 569-73. (c)2016 AACR. PMID- 27197065 TI - Expanded and Activated Natural Killer Cells for Immunotherapy of Hepatocellular Carcinoma. AB - Viral infection of the liver is a major risk factor for hepatocellular carcinoma (HCC). Natural killer (NK) cells recognize virally infected and oncogenically transformed cells, suggesting a therapeutic role for NK-cell infusions in HCC. Using the K562-mb15-41BBL cell line as a stimulus, we obtained large numbers of activated NK cells from the peripheral blood of healthy donors. Expanded NK cells exerted remarkably high cytotoxicity against HCC cell lines, which was generally much higher than that of unstimulated or IL2-activated NK cells. In immunodeficient NOD/scid IL2RGnull mice engrafted with Hep3B, treatment with expanded NK cells markedly reduced tumor growth and improved overall survival. HCC cells exposed for 48 hours to 5 MUmol/L of sorafenib, a kinase inhibitor currently used for HCC treatment, remained highly sensitive to expanded NK cells. HCC cell reductions of 39.2% to 53.8% caused by sorafenib in three cell lines further increased to 80.5% to 87.6% after 4 hours of culture with NK cells at a 1:1 effector-to-target ratio. NK-cell cytotoxicity persisted even in the presence of sorafenib. We found that NKG2D, an NK-cell-activating receptor, was an important mediator of anti-HCC activity. We therefore enhanced its signaling capacity with a chimeric NKG2D-CD3zeta-DAP10 receptor. This considerably increased the anti-HCC cytotoxicity of expanded NK cells in vitro and in immunodeficient mice. The NK expansion and activation method applied in this study has been adapted to clinical-grade conditions. Hence, these results warrant clinical testing of expanded NK-cell infusions in patients with HCC, possibly after genetic modification with NKG2D-CD3zeta-DAP10. Cancer Immunol Res; 4(7); 574-81. (c)2016 AACR. PMID- 27197064 TI - Antitumor Efficacy of Anti-GD2 IgG1 Is Enhanced by Fc Glyco-Engineering. AB - The affinity of therapeutic antibodies for Fcgamma receptors (FcgammaRs) strongly influences their antitumor potency. To generate antibodies with optimal binding and immunologic efficacy, we compared the affinities of different versions of an IgG1 Fc region that had an altered peptide backbone, altered glycans, or both. To produce IgG1 with glycans that lacked alpha1,6-fucose, we used CHO cells that were deficient in the enzyme UDP-N-acetylglucosamine: alpha-3-d-mannoside-beta 1,2-N-acetylglucosaminyltransferase I (GnT1), encoded by the MGAT1 gene. Mature N linked glycans require this enzyme, and without it, CHO cells synthesize antibodies carrying only Man5-GlcNAc2, which were more effective in antibody dependent cell-mediated cytotoxicity (ADCC). Our engineered IgG1, hu3F8-IgG1, is specific for GD2, a neuroendocrine tumor ganglioside. Its peptide mutant is IgG1 DEL (S239D/I332E/A330L), both produced in wild-type CHO cells. When produced in GnT1-deficient CHO cells, we refer to them as IgG1n and IgG1n-DEL, respectively. Affinities for human FcgammaRs were measured using Biacore T-100 (on CD16 and CD32 polymorphic alleles), their immunologic properties compared for ADCC and complement-mediated cytotoxicity (CMC) in vitro, and pharmacokinetics and antitumor effects were compared in vivo in humanized mice. IgG1n and IgG1n-DEL contained only mannose and acetylglucosamine and had preferential affinity for activating CD16s, over inhibitory CD32B, receptors. In vivo, the antitumor effects of IgG1, IgG1-DEL, and IgG1n-DEL were similar but modest, whereas IgG1n was significantly more effective (P < 0.05). Thus, IgG1n antibodies produced in GnT1-deficient CHO cells may have potential as improved anticancer therapeutics. Cancer Immunol Res; 4(7); 631-8. (c)2016 AACR. PMID- 27197067 TI - Molecular Drivers of the Non-T-cell-Inflamed Tumor Microenvironment in Urothelial Bladder Cancer. AB - Muscle-invasive urothelial bladder cancer is a common malignancy with poor outcomes for which immune checkpoint blockade is now showing promise. Despite clinical activity of PD-1/PD-L1-targeted therapy in this disease, most patients do not benefit and resistance mechanisms remain unknown. The non-T-cell-inflamed tumor microenvironment correlates with poor prognosis and resistance to immunotherapies. In this study, we determined tumor-oncogenic pathways correlating with T-cell exclusion. We first establish in this report that T-cell inflamed bladder tumors can be identified by immune gene expression profiling with concordance with CD8(+) T-cell infiltration. Upregulation of genes encoding immune checkpoint proteins PD-L1, IDO, FOXP3, TIM3, and LAG3 was associated with T-cell-inflamed tumors, suggesting potential for sensitivity to checkpoint blockade. beta-Catenin, PPAR-gamma, and FGFR3 pathways were activated in non-T cell-inflamed tumors. No difference was seen in overall somatic mutational density between groups. The three pathways identified represent targetable potential pathways of tumor-intrinsic immunotherapy resistance. Cancer Immunol Res; 4(7); 563-8. (c)2016 AACR. PMID- 27197066 TI - Immunogenic Subtypes of Breast Cancer Delineated by Gene Classifiers of Immune Responsiveness. AB - The abundance and functional orientation of tumor-infiltrating lymphocytes in breast cancer is associated with distant metastasis-free survival, yet how this association is influenced by tumor phenotypic heterogeneity is poorly understood. Here, a bioinformatics approach defined tumor biologic attributes that influence this association and delineated tumor subtypes that may differ in their ability to sustain durable antitumor immune responses. A large database of breast tumor expression profiles and associated clinical data was compiled, from which the ability of phenotypic markers to significantly influence the prognostic performance of a classification model that incorporates immune cell-specific gene signatures was ascertained. Markers of cell proliferation and intrinsic molecular subtype reproducibly distinguished two breast cancer subtypes that we refer to as immune benefit-enabled (IBE) and immune benefit-disabled (IBD). The IBE tumors, comprised mostly of highly proliferative tumors of the basal-like, HER2-enriched, and luminal B subtypes, could be stratified by the immune classifier into significantly different prognostic groups, while IBD tumors could not, indicating the potential for productive engagement of metastasis-protective immunity in IBE tumors, but not in IBD tumors. The prognostic stratification in IBE was independent of conventional variables. Gene network analysis predicted the activation of TNFalpha/IFNgamma signaling pathways in IBE tumors and the activation of the transforming growth factor-beta pathway in IBD tumors. This prediction supports a model in which breast tumors can be distinguished on the basis of their potential for metastasis-protective immune responsiveness. Whether IBE and IBD represent clinically relevant contexts for evaluating sensitivity to immunotherapeutic agents warrants further investigation. Cancer Immunol Res; 4(7); 600-10. (c)2016 AACR. PMID- 27197069 TI - Fasting for haemostasis in children with gastrointestinal bleeding. AB - BACKGROUND: Gastrointestinal bleeding refers to loss of blood from any site of the digestive tract. In paediatric clinical practice, it is usually a complaint of children attending the emergency department as a symptom of diseases such as ulcers, gastric or oesophageal varices, gastritis, Mallory-Weiss tears, anorectal fissures, allergic colitis, infectious colitis, intussusception, Henoch-Schonlein purpura, and Meckel's diverticulum; it also occurs with high incidence in critically ill children hospitalised in intensive care units and is caused by stress-induced gastropathy. No matter what the cause of gastrointestinal bleeding, fasting is believed to be necessary due to the fear that eating may affect haemostasis or aggravate bleeding. OBJECTIVES: To assess the effects and safety of fasting for haemostasis in gastrointestinal bleeding in children. SEARCH METHODS: We searched EBM Reviews - the Cochrane Central Register of Controlled Trials (CENTRAL) (May 2016), Ovid MEDLINE(R) (1946 to 3 May 2016), EMBASE (1980 to 2016 Week 18), Chinese Biomedical Database (CBM) (1978 to 3 May 2016), China National Knowledge Infrastructure (CNKI) (1979 to 3 May 2016), VIP Database (1989 to 4 May 2016) and Wanfang Data (1990 to 4 May 2016). We used no restrictions on language or study setting and limited searches in CNKI and Wanfang Data to the medical field. SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs in children with gastrointestinal bleeding that compared fasting with feeding. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the literature search results, and there were no disagreements. MAIN RESULTS: We identified no RCTs or quasi-RCTs that compared the effects and safety of fasting with feeding for haemostasis in children with gastrointestinal bleeding. No study fulfilled the criteria for considering studies for our review. AUTHORS' CONCLUSIONS: There is currently no information available from RCTs or quasi-RCTs to support or refute the use of fasting for haemostasis in children with gastrointestinal bleeding. PMID- 27197068 TI - Preserved Activity of CD20-Specific Chimeric Antigen Receptor-Expressing T Cells in the Presence of Rituximab. AB - CD20 is an attractive immunotherapy target for B-cell non-Hodgkin lymphomas, and adoptive transfer of T cells genetically modified to express a chimeric antigen receptor (CAR) targeting CD20 is a promising strategy. A theoretical limitation is that residual serum rituximab might block CAR binding to CD20 and thereby impede T cell-mediated anti-lymphoma responses. The activity of CD20 CAR-modified T cells in the presence of various concentrations of rituximab was tested in vitro and in vivo CAR-binding sites on CD20(+) tumor cells were blocked by rituximab in a dose-dependent fashion, although at 37 degrees C blockade was incomplete at concentrations up to 200 MUg/mL. T cells with CD20 CARs also exhibited modest dose-dependent reductions in cytokine secretion and cytotoxicity, but not proliferation, against lymphoma cell lines. At rituximab concentrations of 100 MUg/mL, CAR T cells retained >=50% of baseline activity against targets with high CD20 expression, but were more strongly inhibited when target cells expressed low CD20. In a murine xenograft model using a rituximab refractory lymphoma cell line, rituximab did not impair CAR T-cell activity, and tumors were eradicated in >85% of mice. Clinical residual rituximab serum concentrations were measured in 103 lymphoma patients after rituximab therapy, with the median level found to be only 38 MUg/mL (interquartile range, 19-72 MUg/mL). Thus, despite modest functional impairment in vitro, the in vivo activity of CD20-targeted CAR T cells remains intact at clinically relevant levels of rituximab, making use of these T cells clinically feasible. Cancer Immunol Res; 4(6); 509-19. (c)2016 AACR PMID- 27197070 TI - Impact of Genetic and Epigenetic Variations Within the FADS Cluster on the Composition and Metabolism of Polyunsaturated Fatty Acids in Prostate Cancer. AB - BACKGROUND: In vitro and experimental animal studies have demonstrated that high levels of omega-6 (n-6) polyunsaturated fatty acids (PUFAs) and high ratios of n 6 to omega-3 (n-3) PUFAs are strongly associated with the development and progression of prostate cancer (PCA). However, epidemiological studies in humans have demonstrated inconsistent findings linking dietary PUFAs and PCA risk. We hypothesize that genetic and epigenetic variations within the fatty acid desaturase (FADS) gene cluster produce gene-diet interactions that may explain these disparate findings. This study tested the relationship of the genotype of a single nucleotide polymorphism, rs174537, and the methylation status of a CpG site, cg27386326, with PUFA composition, and markers of PUFA biosynthesis in PCA tissue. METHODS: Sixty PCA specimens from patients undergoing radical prostatectomy were genotyped, pyrosequenced and quantitated for fatty acids (FAs). RESULTS: Long-chain (LC)-PUFAs, such as arachidonic acid (ARA), were abundant in these specimens, with ARA accounting for 15.8% of total FAs. In addition, there was a positive association of the G allele at rs174537 with concentrations of ARA and adrenic acid and ratios of products to precursors within the n-6 PUFA pathway such that specimens from homozygous G individuals exhibited increasingly higher values as compared to specimens from heterozygous individuals and homozygous T individuals. Finally, the methylation status of cg27386326 was inversely correlated with tissue concentrations of LC-PUFAs and markers of LC-PUFA biosynthesis. CONCLUSIONS: These data reveal that genetic and epigenetic variations within the FADS cluster are highly associated with LC-PUFA concentrations and LC-PUFA biosynthetic capacity in PCA tissue. They also raise the potential that gene-PUFA interactions play an important role in PCA risk and severity. Prostate 76:1182-1191, 2016. (c) 2016 The Authors. The Prostate published by Wiley Periodicals, Inc. PMID- 27197072 TI - Visual Impairment and Blindness in Adults in the United States: Demographic and Geographic Variations From 2015 to 2050. AB - IMPORTANCE: The number of individuals with visual impairment (VI) and blindness is increasing in the United States and around the globe as a result of shifting demographics and aging populations. Tracking the number and characteristics of individuals with VI and blindness is especially important given the negative effect of these conditions on physical and mental health. OBJECTIVES: To determine the demographic and geographic variations in VI and blindness in adults in the US population in 2015 and to estimate the projected prevalence through 2050. DESIGN, SETTING, AND PARTICIPANTS: In this population-based, cross sectional study, data were pooled from adults 40 years and older from 6 major population-based studies on VI and blindness in the United States. Prevalence of VI and blindness were reported by age, sex, race/ethnicity, and per capita prevalence by state using the US Census projections (January 1, 2015, through December 31, 2050). MAIN OUTCOMES AND MEASURES: Prevalence of VI and blindness. RESULTS: In 2015, a total of 1.02 million people were blind, and approximately 3.22 million people in the United States had VI (best-corrected visual acuity in the better-seeing eye), whereas up to 8.2 million people had VI due to uncorrected refractive error. By 2050, the numbers of these conditions are projected to double to approximately 2.01 million people with blindness, 6.95 million people with VI, and 16.4 million with VI due to uncorrected refractive error. The highest numbers of these conditions in 2015 were among non-Hispanic white individuals (2.28 million), women (1.84 million), and older adults (1.61 million), and these groups will remain the most affected through 2050. However, African American individuals experience the highest prevalence of visual impairment and blindness. By 2050, the highest prevalence of VI among minorities will shift from African American individuals (15.2% in 2015 to 16.3% in 2050) to Hispanic individuals (9.9% in 2015 to 20.3% in 2050). From 2015 to 2050, the states projected to have the highest per capita prevalence of VI are Florida (2.56% in 2015 to 3.98% in 2050) and Hawaii (2.35% in 2015 and 3.93% in 2050), and the states projected to have the highest projected per capita prevalence of blindness are Mississippi (0.83% in 2015 to 1.25% in 2050) and Louisiana (0.79% in 2015 to 1.20% in 2050). CONCLUSIONS AND RELEVANCE: These data suggest that vision screening for refractive error and early eye disease may reduce or prevent a high proportion of individuals from experiencing unnecessary vision loss and blindness, decrease associated costs to the US economy for medical services and lost productivity, and contribute to better quality of life. Targeted education and screening programs for non-Hispanic white women and minorities should become increasingly important because of the projected growth of these populations and their relative contribution to the overall numbers of these conditions. PMID- 27197073 TI - Multisensory integration in hemianopia and unilateral spatial neglect: Evidence from the sound induced flash illusion. AB - Recent neuropsychological evidence suggests that acquired brain lesions can, in some instances, abolish the ability to integrate inputs from different sensory modalities, disrupting multisensory perception. We explored the ability to perceive multisensory events, in particular the integrity of audio-visual processing in the temporal domain, in brain-damaged patients with visual field defects (VFD), or with unilateral spatial neglect (USN), by assessing their sensitivity to the 'Sound-Induced Flash Illusion' (SIFI). The study yielded two key findings. Firstly, the 'fission' illusion (namely, seeing multiple flashes when a single flash is paired with multiple sounds) is reduced in both left- and right-brain-damaged patients with VFD, but not in right-brain-damaged patients with left USN. The disruption of the fission illusion is proportional to the extent of the occipital damage. Secondly, a reliable 'fusion' illusion (namely, seeing less flashes when a single sound is paired with multiple flashes) is evoked in USN patients, but neither in VFD patients nor in healthy participants. A control experiment showed that the fusion, but not the fission, illusion is lost in older participants (>50 year-old), as compared with younger healthy participants (<30 year-old). This evidence indicates that the fission and fusion illusions are dissociable multisensory phenomena, altered differently by impairments of visual perception (i.e. VFD) and spatial attention (i.e. USN). The occipital cortex represents a key cortical site for binding auditory and visual stimuli in the SIFI, while damage to right-hemisphere areas mediating spatial attention and awareness does not prevent the integration of audio-visual inputs in the temporal domain. PMID- 27197074 TI - Diagnostic potential of plasma microRNA signatures in patients with deep-vein thrombosis. AB - For excluding deep-vein thrombosis (DVT), a negative D-dimer and low clinical probability are used to rule out DVT. Circulating microRNAs (miRNAs) are stably present in the plasma, serum and other body fluids. Their diagnostic function has been investigated in many diseases but not in DVT. The aims of present study were to assess the diagnostic ability of plasma miRNAs in DVT and to examine their correlation with known markers of hypercoagulability, such as D-dimer and APC-PCI complex. Plasma samples were obtained from 238 patients (aged 16-95 years) with suspected DVT included in a prospective multicentre management study (SCORE). We first performed miRNA screening of plasma samples from three plasma pools containing plasma from 12 patients with DVT and three plasma pools containing plasma from 12 patients without DVT using a microRNA Ready-to-use PCR Panel comprising 742 miRNA primer sets. Thirteen miRNAs that differentially expressed were further investigated by quantitative real-time (qRT)-PCR in the entire cohort. The plasma level of miR-424-5p (p=0.01) were significantly higher, whereas the levels of miR-136-5p (p=0.03) were significantly lower in DVT patients compared to patients without DVT. Receiver-operating characteristic curve analysis showed the area under the curve (AUC) values of 0.63 for miR-424 5p and 0.60 for miR-136-5p. The plasma level of miR-424-5p was associated with both D-dimer and APC-PCI complex levels (p<0.0001 and p=0.001, respectively). In conclusions, these findings indicate that certain miRNAs are associated with DVT and markers of hypercoagulability, though their diagnostic abilities are probably too low. PMID- 27197075 TI - C1-inhibitor efficiently delays clot development in normal human whole blood and inhibits Escherichia coli-induced coagulation measured by thromboelastometry. AB - INTRODUCTION: C1-inhibitor (C1-INH), a serine protease inhibitor in plasma plays a central role in the cross-talk among the complement, coagulation, fibrinolytic and kallikrein-kinin systems. However, previous reports indicate thrombotic risks in children following supraphysiological dosing with C1-INH. OBJECTIVE: To investigate the role of supraphysiological C1-INH concentrations in clot development with and without addition of Escherichia coli (E. coli) in fresh human whole blood using thromboelastometry. MATERIALS AND METHODS: Blood was collected in citrate tubes, and C1-INH (3.0 to 47.6MUM) or human serum albumin (HSA) was added as a control. Activated partial thromboplastin time (aPTT) was analysed in the plasma. The analyses non-activated thromboelastometry (NATEM), extrinsic (EXTEM) or intrinsic thromboelastometry (INTEM) were performed using rotational thromboelastometry. RESULTS: C1-INH increased aPTT 1.8-fold (p< 0.05), whereas HSA had no effect. C1-INH increased NATEM clotting time (CT) from 789s to 2025 s (p< 0.05) in a dose-dependent manner. C1-INH reduced the NATEM alpha angle from 47 to 28 degrees (p<0.05) and increased the NATEM clot formation time from 261s to 595s (p< 0.05). E. coli significantly reduced the NATEM CT after 120min of incubation. C1-INH prevented E. coli-induced activation (p< 0.05). C1-INH significantly increased the INTEM CT (p< 0.05), but had no effect on EXTEM CT. C1 INH (47.6MUM) significantly reduced fibrinolysis measured as NATEM and EXTEM lysis indices LI60. CONCLUSIONS: Supraphysiological C1-INH concentrations have dose-dependent anticoagulant effects in human whole blood in vitro. At very high levels C1-INH also inhibits fibrinolysis. PMID- 27197071 TI - Disorders of lysosomal acidification-The emerging role of v-ATPase in aging and neurodegenerative disease. AB - Autophagy and endocytosis deliver unneeded cellular materials to lysosomes for degradation. Beyond processing cellular waste, lysosomes release metabolites and ions that serve signaling and nutrient sensing roles, linking the functions of the lysosome to various pathways for intracellular metabolism and nutrient homeostasis. Each of these lysosomal behaviors is influenced by the intraluminal pH of the lysosome, which is maintained in the low acidic range by a proton pump, the vacuolar ATPase (v-ATPase). New reports implicate altered v-ATPase activity and lysosomal pH dysregulation in cellular aging, longevity, and adult-onset neurodegenerative diseases, including forms of Parkinson disease and Alzheimer disease. Genetic defects of subunits composing the v-ATPase or v-ATPase-related proteins occur in an increasingly recognized group of familial neurodegenerative diseases. Here, we review the expanding roles of the v-ATPase complex as a platform regulating lysosomal hydrolysis and cellular homeostasis. We discuss the unique vulnerability of neurons to persistent low level lysosomal dysfunction and review recent clinical and experimental studies that link dysfunction of the v ATPase complex to neurodegenerative diseases across the age spectrum. PMID- 27197078 TI - Erratum, Vol. 13, February 25 Release. AB - [This corrects the article DOI: 10.5888/pcd13.150383.]. PMID- 27197076 TI - Zinc Fingers and Homeoboxes 2 (Zhx2) Regulates Sexually Dimorphic Cyp Gene Expression in the Adult Mouse Liver. AB - The mammalian cytochrome P450 (Cyp) gene family encodes a large number of structurally related enzymes that catalyze a variety of metabolic and detoxification reactions. The liver is the primary site of Cyp expression in terms of expression levels and number of expressed genes, consistent with this organ's essential role in metabolism of endogenous and xenobiotic compounds. Many Cyp genes exhibit sexually dimorphic expression. For example, Cyp2a4 is expressed significantly higher in the adult liver of female mice compared to male mice. An exception to this pattern is seen in BALB/cJ mice, where male hepatic Cyp2a4 mRNA levels are substantially elevated compared to male mice of other strains. The Zinc fingers and homeoboxes 2 (Zhx2) protein governs the silencing of several genes in the postnatal liver, including alpha-fetoprotein, H19, and glypican 3. Zhx2 also regulates numerous hepatic genes that govern lipid homeostasis. We previously showed that the Zhx2 gene is mutated in BALB/cJ mice, which led us to consider whether elevated male hepatic Cyp2a4 levels in this strain are due to this Zhx2 mutation. Using mice with a conditional Zhx2 deletion, we show here that the absence of Zhx2 in hepatocytes results in increased Cyp2a4 expression in adult male liver. We extend this finding to show that additional Cyp genes are disregulated in the absence of Zhx2. We also show that mRNA levels of Cyp2a4 and several other female-biased Cyp genes are increased, and male-biased Cyp4a12 is decreased in mouse liver tumors. These data indicate that Zhx2 is a novel regulator of sex-biased Cyp gene expression in the normal and diseased liver. PMID- 27197077 TI - Refined modelling of the short-T2 signal component and ensuing detection of glutamate and glutamine in short-TE, localised, (1) H MR spectra of human glioma measured at 3 T. AB - Short-TE (1) H MRS has great potential for brain cancer diagnostics. A major difficulty in the analysis of the spectra is the contribution from short-T2 signal components, mainly coming from mobile lipids. This complicates the accurate estimation of the spectral parameters of the resonance lines from metabolites, so that a qualitative to semi-quantitative interpretation of the spectra dominates in practice. One solution to overcome this difficulty is to measure and estimate the short-T2 signal component and to subtract it from the total signal, thus leaving only the metabolite signals. The technique works well when applied to spectra obtained from healthy individuals, but requires some optimisation during data acquisition. In the clinical setting, time constraints hardly allow this. Here, we propose an iterative estimation of the short-T2 signal component, acquired in a single acquisition after measurement of the full spectrum. The method is based on QUEST (quantitation based on quantum estimation) and allows the refinement of the estimate of the short-T2 signal component after measurement. Thus, acquisition protocols used on healthy volunteers can also be used on patients without further optimisation. The aim is to improve metabolite detection and, ultimately, to enable the estimation of the glutamine and glutamate signals distinctly. These two metabolites are of great interest in the characterisation of brain cancer, gliomas in particular. When applied to spectra from healthy volunteers, the new algorithm yields similar results to QUEST and direct subtraction of the short-T2 signal component. With patients, up to 12 metabolites and, at least, seven can be quantified in each individual brain tumour spectrum, depending on the metabolic state of the tumour. The refinement of the short-T2 signal component significantly improves the fitting procedure and produces a separate short-T2 signal component that can be used for the analysis of mobile lipid resonances. Thus, in brain tumour spectra, distinct estimates of signals from glutamate and glutamine are possible. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27197079 TI - Snacking on Television: A Content Analysis of Adolescents' Favorite Shows. AB - INTRODUCTION: Snacking is a complex behavior that may be influenced by entertainment media. Research suggests that snacking and unhealthy foods are commonly shown in programming that targets young audiences, but shows selected for study have been limited. We conducted a content analysis on shows that were named as favorites by adolescents to characterize portrayals of snacking on popular television. METHODS: A diverse sample of 2,130 adolescents (mean age, 14.3 y) listed 3 favorite television shows in a 2010 school-based survey. Three episodes each of the 25 most popular shows were coded for food-related content, including healthfulness, portion size, screen time use, setting, and social context. We also analyzed the characteristics of characters involved in eating incidents, the show type, and the show rating. We used chi(2) tests, binomial tests, and multilevel regression models to compare incidence of snacks versus meals, the characteristics of those involved, and snacking across show characteristics. RESULTS: Almost half of food incidents on television shows were snacks. Snacks were significantly more likely than meals to be "mostly unhealthy" (69.3% vs 22.6%, P < .001) and were more likely to include screen time use (25.0% of snacking incidents vs 4.0% of meals, P < .001). Young characters and those coded as being of low socioeconomic status or overweight were overrepresented in snacking incidents. Sitcoms and shows rated for a youth audience were significantly more likely to portray snacking than were shows for adult audiences. CONCLUSION: Media awareness and literacy programs should include foods and snacking behaviors among the issues they address. More healthful portrayals of food and dietary intake in entertainment shows' content would create a healthier media environment for youth. PMID- 27197081 TI - A Qualitative Study of Vape Shop Operators' Perceptions of Risks and Benefits of E-Cigarette Use and Attitude Toward Their Potential Regulation by the US Food and Drug Administration, Florida, Georgia, South Carolina, or North Carolina, 2015. AB - INTRODUCTION: Approximately 8,500 vape shops in the United States sell a variety of electronic nicotine delivery systems (ENDS). This study examined vape shop operators' perceptions of benefits and risk of ENDS use, what they perceive to be the reasons for ENDS use, their source of product information, what information they shared with customers, and the impact of existing and future regulation of ENDS on its use and on their business. METHODS: We conducted qualitative interviews with 20 vape shop operators located in Florida, Georgia, South Carolina, and North Carolina in spring 2015. A semi-structured interview guide was used, and interviews were audio-recorded and transcribed verbatim. The transcripts were analyzed using NVIVO software. RESULT: Vape shop owners perceived ENDS to be less harmful and more economical than conventional cigarettes and indicated that most of their customers used ENDS as a smoking cessation tool. Most owners were former smokers and used ENDS to quit. Shop owners relied on their personal experiences and the Internet for information, and shared information with customers at point of sale by using the shop's website and social media. Most expressed concern that complying with potential regulations, including banning flavors or tax increases, would jeopardize their business. Some felt that ENDS should not be regulated as tobacco products and felt that big tobacco was behind these proposed regulations. Most owners supported age restrictions and quality controls for e-liquid. CONCLUSION: Vape shop owners are in a unique position to serve as frontline consumer educators. Interventions should focus on providing them with current information on benefits and risks of ENDS and information on national, state, and local regulations and compliance requirements. PMID- 27197082 TI - HNA diversity in six subgroups of Orang Asli in Peninsular Malaysia. PMID- 27197080 TI - Who Would Pay for State Alcohol Tax Increases in the United States? AB - INTRODUCTION: Despite strong evidence that increasing alcohol taxes reduces alcohol-related harm, state alcohol taxes have declined in real terms during the past 3 decades. Opponents of tax increases argue that they are unfair to "responsible" drinkers and those who are financially disadvantaged. The objectives of this study were to assess the impact of hypothetical state alcohol tax increases on the cost of alcohol for adults in the United States on the basis of alcohol consumption and sociodemographic characteristics. METHODS: The increased net cost of alcohol (ie, product plus tax) from a series of hypothetical state alcohol tax increases was modeled for all 50 states using data from the 2011 Behavioral Risk Factor Surveillance System, IMPACT Databank, and the Alcohol Policy Information System. Costs were assessed by drinking pattern (excessive vs nonexcessive) and by sociodemographic characteristics. RESULTS: Among states, excessive drinkers would pay 4.8 to 6.8 times as much as nonexcessive drinkers on a per capita basis and would pay at least 72% of aggregate costs. For nonexcessive drinkers, the annual cost from even the largest hypothetical tax increase ($0.25 per drink) would average less than $10.00. Drinkers with higher household incomes and non-Hispanic white drinkers would pay higher per capita costs than people with lower incomes and racial/ethnic minorities. CONCLUSION: State-specific tax increases would cost more for excessive drinkers, those with higher incomes, and non-Hispanic whites. Costs to nonexcessive drinkers would be modest. Findings are relevant to developing evidence-based public health practice for a leading preventable cause of death. PMID- 27197083 TI - Cryoablation with an 8-mm-Tip Catheter for Right-Sided Accessory Pathways in Children. AB - BACKGROUND: Cryoablation is increasingly utilized in children because of its safety profile. Recently, larger catheter tips have been more widely used to improve long-term success rates. The aim of this study was to assess the safety and efficacy of 8-mm-tip catheters for cryoablation of right-sided accessory pathways (APs) in children. METHODS: Electrophysiological procedures were performed using the EnSiteTM system (St. Jude Medical Inc., St. Paul, MN, USA). RESULTS: Between July 2010 and July 2014, 54 patients (mean age: 13.1 +/- 3.7 years) underwent cryoablation using an 8-mm-tip catheter. In 18 of 54 (33%) patients where an 8-mm-tip catheter was the first-choice catheter, the success rate was 18 of 18 (100%). There was a history of previous failed attempts or recurrence with radiofrequency ablation and/or 6-mm-tip cryoablation in 36 of 54 (67%) patients. The success rate in these patients was 24 of 36 (67%). No fluoroscopy was used in 34 of 54 procedures. The recurrence rate was six of 42 (14%) during a mean follow-up period of 32 +/- 15 months. In one patient, transient atrioventricular block occurred. CONCLUSIONS: Cryoablation with an 8-mm tip catheter for right-sided APs in children who weigh over 40 kg appears to be safe and acutely effective in cases where conventional ablation methods fail and also as a first choice for ablation procedure. However, the recurrence rate still seems to be high. PMID- 27197084 TI - Enhanced summer warming reduces fungal decomposer diversity and litter mass loss more strongly in dry than in wet tundra. AB - Many Arctic regions are currently experiencing substantial summer and winter climate changes. Litter decomposition is a fundamental component of ecosystem carbon and nutrient cycles, with fungi being among the primary decomposers. To assess the impacts of seasonal climatic changes on litter fungal communities and their functioning, Betula glandulosa leaf litter was surface-incubated in two adjacent low Arctic sites with contrasting soil moisture regimes: dry shrub heath and wet sedge tundra at Disko Island, Greenland. At both sites, we investigated the impacts of factorial combinations of enhanced summer warming (using open-top chambers; OTCs) and deepened snow (using snow fences) on surface litter mass loss, chemistry and fungal decomposer communities after approximately 1 year. Enhanced summer warming significantly restricted litter mass loss by 32% in the dry and 17% in the wet site. Litter moisture content was significantly reduced by summer warming in the dry, but not in the wet site. Likewise, fungal total abundance and diversity were reduced by OTC warming at the dry site, while comparatively modest warming effects were observed in the wet site. These results suggest that increased evapotranspiration in the OTC plots lowered litter moisture content to the point where fungal decomposition activities became inhibited. In contrast, snow addition enhanced fungal abundance in both sites but did not significantly affect litter mass loss rates. Across sites, control plots only shared 15% of their fungal phylotypes, suggesting strong local controls on fungal decomposer community composition. Nevertheless, fungal community functioning (litter decomposition) was negatively affected by warming in both sites. We conclude that although buried soil organic matter decomposition is widely expected to increase with future summer warming, surface litter decay and nutrient turnover rates in both xeric and relatively moist tundra are likely to be significantly restricted by the evaporative drying associated with warmer air temperatures. PMID- 27197085 TI - Comparative study of disability-free life expectancy across six low- and middle income countries. AB - AIM: There is a knowledge gap about the disability-free life expectancy (DFLE) in low- and middle-income countries. The present study aimed to compute and compare DFLE in six such countries, and examine sex differences in DFLE in each country. METHODS: Based on data from the World Health Organization Study on Global Aging and Adult Health wave 1 survey, we used the Sullivan method to estimate DFLE among persons aged years 50 years and older. Disability was divided into moderate disability and severe disability during the calculation. RESULTS: Of the six countries, China had the highest DFLE and lowest expected average lifetime with disability. India had the lowest DFLE and highest life years with moderate and severe disability. In each country, women live longer than men, but with more disabilities in both absolute and proportional terms. The huge sex difference in Russia requires special attention. In addition, most of the life expectancy lived with disability was spent with severe disability, rather than moderate disability. CONCLUSIONS: The study has shed some light on the disparities across the six countries with regard to DFLE at old ages. The low percentage of DFLE in life expectancy in some countries, such as India, calls for effective policies on healthy aging. The "sex disability-survival paradox" in DFLE is supported by our results. To differentiate the severity of disability should be routine in calculating DFLE. Geriatr Gerontol Int 2017; 17: 637-644. PMID- 27197086 TI - Nanoscopic voltage distribution of operating cascade laser devices in cryogenic temperature. AB - A nanoscopic exploratory measurement technique to measure voltage distribution across an operating semiconductor device in cryogenic temperature has been developed and established. The cross-section surface of the terahertz (THz) quantum cascade laser (QCL) has been measured that resolves the voltage distribution at nanometer scales. The electric field dissemination across the active region of the device has been attained under the device's lasing conditions at cryogenic temperature of 77 K. PMID- 27197088 TI - A simple approach for bioactive surface calibration using evanescent waves. AB - When investigating the interaction of cells with surfaces, it is becoming increasingly important to perform quantitative measurements of surface protein density to understand reaction kinetics. Previously, to calibrate a surface for an experiment one would have to use a radiometric assay or strip the surface with acid and perform a mass quantification. Although both of these methodologies have been proven to be effective measurement techniques for surface quantification, they can be time consuming and require substantial amounts of material. The latter is particularly problematic when working with specialized molecules or constructs that may be expensive to produce and/or only available in small quantities. Here we present a simple method to measure the intensity and penetration depth of an evanescent wave, and use this information to quantify the density of surface molecules in a microscopic region of a transparent surface. PMID- 27197087 TI - Enamel alteration following tooth bleaching and remineralization. AB - The purpose of this study was to compare the effects of professional tooth whitening agents containing highly concentrated hydrogen peroxide (with and without laser activation), on the enamel surface; and the potential of four different toothpastes to remineralize any alterations. The study was performed on 50 human molars, divided in two groups: treated with Opalescence((r)) Boost and Mirawhite((r)) Laser Bleaching. Furthermore, each group was divided into five subgroups, a control one and 4 subgroups remineralized with: Mirasensitive((r)) hap+, Mirawhite((r)) Gellee, GC Tooth MousseTM and Mirafluor((r)) C. The samples were analysed by SEM/3D-SEM-micrographs, SEM/EDX-qualitative analysis and SEM/EDX semiquantitative analysis. The microphotographs show that both types of bleaching cause alterations: emphasized perikymata, erosions, loss of interprizmatic substance; the laser treatment is more aggressive and loss of integrity of the enamel is determined by shearing off the enamel rods. In all samples undergoing remineralization deposits were observed, those of toothpastes based on calcium phosphate technologies seem to merge with each other and cover almost the entire surface of the enamel. Loss of integrity and minerals were detected only in the line-scans of the sample remineralized with GC Tooth MousseTM. The semiquantitative EDX analysis of individual elements in the surface layer of the enamel indicates that during tooth-bleaching with HP statistically significant loss of Na and Mg occurs, whereas the bleaching in combination with a laser leads to statistically significant loss of Ca and P. The results undoubtedly confirm that teeth whitening procedures lead to enamel alterations. In this context, it must be noted that laser bleaching is more aggressive for dental substances. However, these changes are reversible and can be repaired by application of remineralization toothpastes. PMID- 27197089 TI - Non-injection synthesis of monodisperse Cu-Fe-S nanocrystals and their size dependent properties. AB - It is demonstrated that ternary Cu-Fe-S nanocrystals differing in composition (from Cu-rich to Fe-rich), structure (chalcopyrite or high bornite) and size can be obtained from a mixture of CuCl, FeCl3, thiourea and oleic acid (OA) in oleylamine (OLA) using the heating up procedure. This new preparation method yields the smallest Cu-Fe-S nanocrystals ever reported to date (1.5 nm for the high bornite structure and 2.7 nm for the chalcopyrite structure). A comparative study of nanocrystals of the same composition (Cu1.6Fe1.0S2.0) but different in size (2.7 nm and 9.3 nm) revealed a pronounced quantum confinement effect, confirmed by three different techniques: UV-vis spectroscopy, cyclic voltammetry and Mossbauer spectroscopy. The optical band gap increased from 0.60 eV in the bulk material to 0.69 eV in the nanocrystals of 9.3 nm size and to 1.39 eV in nanocrystals of 2.7 nm size. The same trend was observed in the electrochemical band gaps, derived from cyclic voltammetry studies (band gaps of 0.74 eV and 1.54 eV). The quantum effect was also manifested in Mossbauer spectroscopy by an abrupt change in the spectrum from a quadrupole doublet to a Zeeman sextet below 10 K, which could be interpreted in terms of the well defined energy states in these nanoparticles, resulting from quantum confinement. The Mossbauer spectroscopic data confirmed, in addition to the results of XPS spectroscopy, the co-existence of Fe(iii) and Fe(ii) in the synthesized nanocrystals. The organic shell composition was investigated by NMR (after dissolution of the inorganic core) and IR spectroscopy. Both methods identified oleylamine (OLA) and 1 octadecene (ODE) as surfacial ligands, the latter being formed in situ via an elimination-hydrogenation reaction occurring between OLA and the nanocrystal surface. PMID- 27197090 TI - Cumulative Training Dose's Effects on Interrelationships Between Common Training Load Models During Basketball Activity. AB - PURPOSE: The influence of various factors on training-load (TL) responses in basketball has received limited attention. This study aimed to examine the temporal changes and influence of cumulative training dose on TL responses and interrelationships during basketball activity. METHODS: Ten state-level Australian male junior basketball players completed 4 * 10-min standardized bouts of simulated basketball activity using a circuit-based protocol. Internal TL was quantified using the session rating of perceived exertion (sRPE), summated heart rate zones (SHRZ), Banister training impulse (TRIMP), and Lucia TRIMP models. External TL was assessed via measurement of mean sprint and circuit speeds. Temporal TL comparisons were performed between 10-min bouts, while Pearson correlation analyses were conducted across cumulative training doses (0-10, 0-20, 0-30, and 0-40 min). RESULTS: sRPE TL increased (P < .05) after the first 10-min bout of basketball activity. sRPE TL was only significantly related to Lucia TRIMP (r = .66-.69; P < .05) across 0-10 and 0-20 min. Similarly, mean sprint and circuit speed were significantly correlated across 0-20 min (r = .67; P < .05). In contrast, SHRZ and Banister TRIMP were significantly related across all training doses (r = .84-.89; P < .05). CONCLUSIONS: Limited convergence exists between common TL approaches across basketball training doses lasting beyond 20 min. Thus, the interchangeability of commonly used internal and external TL approaches appears dose-dependent during basketball activity, with various psychophysiological mediators likely underpinning temporal changes. PMID- 27197091 TI - A Budget Proposal for China's Public Long-Term Care Policy. AB - Long-term care (LTC) policy is at an experimental stage in China, characterized by various regional pilot programs. The public cost of LTC is difficult to estimate due to a lack of clarity about policy detail from the central government. This article analyzes the current disabled status for vulnerable older people without sufficient financial resources and family supports. It focuses on estimating a safety net public subsidy policy for LTC services in China, both for today and into the future, using China Health and Retirement Longitudinal Survey (CHARLS) data, 2011 wave, with the methods of multinomial logistic regression and simulation. The key contribution is to estimate the future disability trend and LTC public cost based on changes in education, population ageing, and urbanization. Disability prevalence might be decreasing partly due to higher education, urbanization, and better health care, and the overall public LTC costs might be growing by the results of projection. PMID- 27197092 TI - Examining local processes when applying a cumulative impact policy to address harms of alcohol outlet density. AB - One approach to addressing the negative health and social harms of excessive drinking has been to attempt to limit alcohol availability in areas of high outlet density. The Licensing Act (2003) enables English local authorities the power to implement a Cumulative Impact Policy (CIP) in order to tackle alcohol challenges. More than 100 English local authorities have implemented a CIP in one or more designated areas. We examined local licence decision-making in the context of implementing CIPs. Specifically, we explored the activities involved in alcohol licensing in one London local authority in order to explicate how local decision-making processes regarding alcohol outlet density occur. Institutional ethnographic research revealed that CIPs were contested on multiple grounds within the statutory licensing process of a local authority with this policy in place. CIPs are an example of multi-level governance in which national and local interests, legal powers and alcohol licensing priorities interface. Public health priorities can be advanced in the delivery of CIPs, but those priorities can at times be diluted by those of other stakeholders, both public sector and commercial. PMID- 27197093 TI - Hepatocellular carcinoma: How can we move from racial/ethnic disparities to a model of health equity? PMID- 27197094 TI - Cutting-Edge Techniques for Mycotoxin Analysis. PMID- 27197095 TI - [Where internists work?]. AB - For health institutions, knowing the fate of human resources within their classrooms is an extremely complicated task. Within the Instituto Mexicano del Seguro Social, where most specialists are trained in our country, with a clear orientation towards the pursuit of excellence and satisfaction of their needs human resources for health in Mexico is provided, hence the need to identify the professional profile and career destination of its graduates, which will be useful in the training of human resources for health. PMID- 27197096 TI - [Threshold value of f/Vt index for predicting successful weaning from mechanical ventilation in active smokers]. AB - BACKGROUND: Mechanical ventilation (MV) is used in 60-70 % of patients admitted to the intensive care unit (ICU). An f/Vt threshold value of 105 is a predictor of successful weaning from mechanical ventilation (WMV) in patients with asthma, cardiac surgery, pneumonia, sepsis, neurocritical, etc. However, there are no reports about the usefulness of the f/Vt value to predict successful WMV in patients with active smoking (AS). The purpose of this paper is to identify a threshold value for f/Vt to predict successful WMV in patients with AS. METHODS: Prospectively, 85 patients with AS and MV >24 hours admitted to de ICU were included. Demographic and clinical data were registered. The f/Vt value was measured with a Wright's spirometer, and the sensibility, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated to predict a successful WMV. A p value <0.05 was considered statistically significant. RESULTS: The average of f/Vt was 68.69. Successful WMV was of 75.3 %. An f/Vt threshold value of 79.5 had sensibility of 76 %, specificity of 61 %, PPV of 85 %, and NPV of 46 % to predict successful WMV in this group of patients. CONCLUSIONS: An f/Vt threshold value of 79.5 is useful to predict successful WMV in patients with AS. PMID- 27197097 TI - [Chronic low back pain and associated risk factors, in patients with social security medical attention: A case-control study]. AB - BACKGROUND: Chronic low back pain (CLBP) is frequently seen in the orthopedic outpatient consultation. The aim of this paper is to identify risk factors associated with CLBP in patients cared for during the year 2012, at a General Hospital belonging to Instituto Mexicano del Seguro Social, in Yucatan, Mexico. METHODS: Data of 95 patients with CLBP (cases) was compared with data of 190 patients without CLBP (controls) using a binary logistic model (BLM), from which odd ratios (OR) and 95 % confidence intervals (95 % CI) were obtained. RESULTS: School level, body mass index (BMI) as a continuous variable, story of heavy weight lifting, some types of comorbidities and dyslipidemia, were identified as statistically significant in the bivariate analysis (p <= 0.05 each). In a second step, secondary school level (OR 0.25, 95 % CI: 0.08-0.81), dyslipidemia (OR 0.26, 95 % CI: 0.12-0.56), heavy weights lifting (OR 0.22, 95 % CI: 0.12-0.42), and BMI (OR 1.22, 95 % CI: 1.12-1.32) were all identified by the BLM as statistically significant. CONCLUSIONS: In this sample, secondary school level, dislipidemia and heavy weights lifting reduced the risk of CLBP, while the BMI increased the risk. PMID- 27197098 TI - [Depression prevalence among end stage renal disease patients in maintenance hemodialysis]. AB - BACKGROUND: Depression is a common morbidity in end- stage kidney disease (ESKD) patients and impacts negatively on treatment outcomes. This study aimed to assess the prevalence of depression among Mexican ESKD patients in maintenance hemodialysis (MHD) and to evaluate the relationship with elapsed time (< 1 year or >= 1 year) since the beginning of therapy. METHODS: A cross-sectional study took place in a urban hospital from the Mexican Institute of Social Security and 81 subjects aged 30 - 69 years old were enrolled. Beck depression inventory (BDI) was applied and a stratified analysis was made. RESULTS: The overall prevalence of depression (>= 16 points, BDI) was 42.0 % and 35.6 % and 50.0 % in the group with < 1 and >= 1 year on treatment respectively (p = 0.191). CONCLUSIONS: Our findings suggest that depression prevalence is high among adult patients undergoing MHD and it seems to be independent from elapsed time since the beginning of therapy. PMID- 27197099 TI - [Infective endocarditis. 5-years experience in a third-level reference center in Yucatan, Mexico]. AB - BACKGROUND: Infective endocarditis is a disease with high morbidity and mortality. The clinical characteristics differ among populations. Therefore it is important to know the characteristics of the disease in our region. METHODS: This is an observational study that included all patients diagnosed with infective endocarditis from 1 January 2009 until 31 December 2014. The data are showed as frequencies and percentages altogether with medians with interquartile range. RESULTS: 10 cases were included. The median age was 34 years (IQR 26-41). Several risk factors were identified and included: previous valvular heart disease, patients with chronic kidney disease who have had a vascular access and previous history of immunological disease. The native mitral valve was the most affected. The size of vegetations had a median length of 14 mm (IQR 9.3-16). Streptococcus alpha hemolytic was the most common organism. In-hospital mortality rate was 10 %. CONCLUSIONS: The behavior of the disease is similar to other national series. We identify risk factors that could be related to the type of morbidities in the region. PMID- 27197100 TI - [Diet and polymer standard vs. standard in the nutritional status of elderly patients with fragility]. AB - BACKGROUND: The elderly patients with fragility show different physiological changes, so they are given polymeric diets to maintain and/or alter their nutritional status. The aim of this paper is to demonstrate the effect of changing a standard polymeric diet and a standard diet on nutritional status in elderly patients with fragility. METHODS: Clinical randomized controlled trial in 23 elderly patients, 70 years of age or older, with fragility, hospitalized in a Internal Medicine Unity in a period from July to December 2014. Nutritional status was determined through Minimum Nutritional Consulting (MNA) and body mass index (BMI). Descriptive statistics, Chi square, Student t test and McNemar. RESULTS: In the G1: 12 patients were in the G2 and 11, a positive change was observed in the nutritional status G1 initially being 14.00 (malnutrition) and end 22.75 (risk of malnutrition). According to BMI (kg/m2) was evident at the beginning 25 % of patients (3) with mild malnutrition, but the final results show figures with a zero percentage of malnourished patients. CONCLUSIONS: The use of standard polymeric diet increases body weight, BMI and nutritional status in elderly patients with fragility. PMID- 27197101 TI - [End stage renal disease lymphopenia; characterization and clinical correlation]. AB - BACKGROUND: Patients with End Stage Renal Disease (ESRD), defined as those in Stage 5 of the Kidney Disease Outcome Quality Initiative (KDOQI) classification, have a number of acquired immune deficiencies secondary to the uremic stage, among them lymphopenia. In the present report, we retrospectively characterized the peripheral blood lymphocyte counts in a group of patients with ESRD and we related lymphopenia to their biochemical parameters and to the presence or absence of infections. METHODS: Medical records from 190 patients in ESRD were selected from 282 medical records of patients being treated between February 2008 and November 2012 for kidney failure at different stages. A number of variables, including lymphocyte counts, biochemical parameters and infections, were analyzed at two different time points: Before and during dialysis. RESULTS: ESRD patients analyzed had a well defined peripheral blood hematological pattern, characterized by severe chronic anemia, normal or elevated leukocyte count and normal or below normal lymphocyte count. The degree of hematological changes correlated with the depth of renal dysfunction and improved with dialysis along with the improvement of urea and creatinine values. CONCLUSIONS: Lymphopenia was present in around half ESRD patients and was associated with increased infections, but they were of the same type as those present in ESRD patients without lymphopenia. Infections were different as those commonly associated with other immune deficiency lymphopenias. The implications of these findings are discussed. PMID- 27197102 TI - [Verapamil in conjunction with pressure therapy in the treatment of pathologic scar due burn injury]. AB - BACKGROUND: Keloids and hypertrophic scars are dermal fibro-proliferative disorders unique to humans. Their treatment is a true challenge with multiple options, but not all the time with good results. Unfortunately this problem is not uncommon in patients with history of burn injury. The aim of this article is to evaluate the use of verapamil and pressure garments in patients with hypertrophic or keloid scar caused by burn injury. METHODS: We included patients with a hypertrophic or keloid scar caused by burn injury candidate to treatment with pressure garment. The pathologic scars were evaluated by serial photographic records, Vancouver and Posas scales. The scales of Vancouver and Posas were compared with t Student. RESULTS: We included 13 scars in 11 patients. Four scars were located in the legs, 4 in the arms, 4 in the face-neck and 1 in the abdomen. The dose of verapamil was calculated .03mg per kg. Injections were scheduled every 7 to 10 days until complete 6 sessions. Taking in count Posas scale, patients referred improvement in pigmentation (.01), thickness (.005), pliability (.01) and surface area (.004). In the Vancouver scale the observers mentioned improvement in elevation (.008), pigmentation (.014), vascularity (.022), flexibility (.014) and pruritus (.003). No adverse effects were found in verapamil injection. CONCLUSIONS: Verapamil was useful in conjunction with pressure garment to improve the condition of the keloid and hypertrophic scar caused by burn. PMID- 27197103 TI - [Treatment of interdigital foot Erythrasma with ozonated olive oil]. AB - BACKGROUND: Erythrasma is caused by Corinebacterium minutissimum producing a porphyrin that with Wood's light emits a coral-red fluorescence. It is the most common bacterial infection of the feet. Ozonated olive oil decreases the cytoplasm and damages bacterial proteins and lipids. Treatment is with oral erythromycin and there is no consensus regarding the topical therapy of choice. The aim of this paper is to evaluate the therapeutic efficacy of ozonated olive oil in a pilot trial for Erythrasma. METHODS: Experimental, open, observational, descriptive, longitudinal clinical trial at the section of Mycology, of the General Hospital "Dr. Manuel Gea Gonzalez". PATIENTS: 10 individuals with interdigital feet Erythrasma. INTERVENTION: ozonated olive oil every 12 hours for 10 days was given. RESULTS: All patients had disappearance of coral-red fluorescence, erythema, fissures, pruritus, and maceration; two patients persisted with scaling. A cure was obtained in 100 % of patients, similar to oral erythromycin response. CONCLUSIONS: Ozonated olive oil is a good topical treatment option for interdigital Erythrasma avoiding oral medications. Larger studies are required. PMID- 27197104 TI - [Antibibiotic resistance by nosocomial infections' causal agents]. AB - BACKGROUND: The antibibiotic resistance by nosocomial infections (NI) causal agents constitutes a seriously global problematic that involves the Mexican Institute of Social Security's Regional General Hospital 1 in Chihuahua, Mexico; although with special features that required to be specified and evaluated, in order to concrete an effective therapy. METHODS: Observational, descriptive and prospective study; by means of active vigilance all along 2014 in order to detect the nosocomial infections, for epidemiologic study, culture and antibiogram to identify its causal agents and antibiotics resistance and sensitivity. RESULTS: Among 13527 hospital discharges, 1079 displayed NI (8 %), standed out: the related on vascular lines, of surgical site, pneumonia and urinal track; they added up two thirds of the total. We carried out culture and antibiogram about 300 of them (27.8 %); identifying 31 bacterian species, mainly seven of those (77.9 %): Escherichia coli, Staphylococcus aureus and epidermidis, Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae and Enterobacter cloacae; showing multiresistance to 34 tested antibiotics, except in seven with low or without resistance at all: vancomycin, teicoplanin, linezolid, quinupristin-dalfopristin, piperacilin-tazobactam, amikacin and carbapenems. CONCLUSIONS: When we contrasted those results with the recommendations in the clinical practice guides, it aroused several contradictions; so they must be taken with reserves and has to be tested in each hospital, by means of cultures and antibiograms in practically every case of nosocomial infection. PMID- 27197105 TI - [Lower extremity amputation rates in diabetic patients]. AB - BACKGROUND: The lower extremity amputations diminish the quality of life of patients with Diabetes Mellitus (DM). The aim of this study was to describe the lower extremity amputation rates in subjects with DM in the Mexican Social Security Institute (IMSS), comparing 2004 and 2013. METHODS: A comparative cross sectional study was done. Amputations were identified from the hospital records of System of Medical Statistics (DataMart). The DM patient census was obtained from the System of Integral Attention to Health. Major and minor amputations rates were expressed per 100,000 DM patients. RESULTS: We observed 2 334 340 and 3 416 643 DM patients during 2004 and 2013, respectively. The average age at the time of the amputation was similar in 2004 and 2013 (61.7 and 65.6 years old for minor and major amputations respectively). The major amputations rates were 100.9 and 111.1 per 100 000 subjects with DM in during 2004 and 2013 (p = 0.001); while minor amputations rates were 168.8 and 162.5 per 100 000 subjects with DM in during 2004 and 2013 respectively (p = 0.069). CONCLUSIONS: The lower extremity amputations rates at IMSS are very high compared with that reported in developed countries. The major amputations rate increased in 2013 compared with 2004. PMID- 27197107 TI - [Evolution of the type 2 diabetes mellitus epidemia in insured population at the IMSS]. AB - BACKGROUND: The global increase in type 2 diabetes mellitus (T2DM) is requiering higher demands in health institutions; It is a global emergency because of overspending that threaten social security, and kidney complications and cardiovascular damage, which affects millions enfermos.1 The aim of this work is to characterize the epidemic of T2DM with metabolic syndrome and define the institutional response containment-control universal educational interventions healthy lifestyles to prevent premature death and disability from ischemic heart disease (IHD), cerebrovascular disease (CVD), end stage renal disease ( IRT), blindness and amputations. METHODS: A review of the years 1990-2013: Epidemiological Bulletin; consultation services: Family Medicine, Specialties, Emergency, Hospitalization, and prevention studies estimate of expenditure and institutional savings. RESULTS: 48 % increase incidence, prevalence increased from 7 to 10.6 %, and mortality from 35.6 to 77.2 per 100 000 inhabitants. Hypertension, and deaths, and EVC CI, increased 58, 197, 142.5 % respectively. Consultations in 2013 were 9113 082. The estimate of expenditure for prediabetes screening and medical care to prevent complications saves near of 60 % of current expenditure. CONCLUSIONS: Control the epidemic by training patients, families and staff health healthy lifestyle is the treatment to revert to normal BMI, glucose, triglycerides, HDL cholesterol, LDL cholesterol, blood pressure and addictions to snuff / alcohol, to decelerate complications of the metabolic syndrome. PMID- 27197106 TI - [Biofeedback treatment for acute whiplash patients]. AB - BACKGROUND: The aim of this study is to evaluate the physiological and psychological effect after an electromyographic biofeedback treatment in combination with progressive muscular relaxation training in patients with acute whiplash. METHODS: Twelve patients with acute whiplash volunteered to participate in a quasi-experimental design and a control group. INCLUSION CRITERIA: Two months maximum after car accident, severity levels II and I. EXCLUSION CRITERIA: previous history of persistent pain or serious previous injury. The groups were randomly divided in two (treatment and waiting list groups). We used electromyographic measures of the trapezius muscles with psychometric tests: Beck Anxiety and Depression Inventory; Oswestry Pain Disability Questionnaire; Visual Analog Scale of Pain; TAMPA Scale for Kinesiophobia. The treatment consisted in electromyographic biofeedback after progressive muscular relaxation training. RESULTS: There were significant intra-group differences before and after treatment in muscular symmetry and subjective pain perception in the treatment group. CONCLUSIONS: We achieved a significant change (clinical and statistical) in subjective pain perception and muscular symmetry. This study highlights the importance of multidisciplinary work in acute pain patients and the effectiveness of clinical psychophysiological strategies with acute whiplash patients. PMID- 27197108 TI - [Genetic isolates and inbreeding customs in three rural municipalities from Honduras]. AB - BACKGROUND: The isonymic method has been amply used to assess the approximate genetic structure of human communities. The objective of the study was to evaluate the magnitude of genetic isolation and inbreeding customs in 57 communities from three rural municipalities of Honduras using isonymy techniques. METHODS: The list of 408 different surnames from 20712 voters registered in the national electoral organism, residing in the 57 Honduran communities, was used for this study. For each community, random (IR), non-random (IN), and total (IT) isonymy values were calculated in order to assess inbreeding coefficients FST, FIS and FIT. RESULTS: High consanguinity due to isolation and to endogamous customs was unveiled in many communities. Significant deviation from the exogamous behavior typical of many human populations was observed in the three studied municipalities, when compared to other Honduran populations. CONCLUSIONS: The studied communities present high consanguinity due to isolation, ethnic segregation and/or endogamous customs. PMID- 27197109 TI - [Obesity in children and its relationship with chronic kidney disease]. AB - In the last decades, obesity and chronic kidney disease (CKD) have increased worldwide, in parallel. This article focuses on the current issues of obesity on renal damage, with special emphasis on what happens at pediatric ages. While obesity has been linked closely with type 2 diabetes mellitus and hypertension, reduced insulin sensitivity is a direct mechanism for renal damage. The pathophysiologic mechanisms on renal damage include glomerular hyperfiltration and hypertrophy, hypercellularity and broadening of the mesangial regions, while the lack of sensitivity to insulin increases the effects of angiotensin II, exacerbates proteinuria and induces the production of inflammatory cytokines. Many epidemiological studies have documented the relationship of increased BMI with the development of ERC, but most of these studies have been conducted in adults. In children, the information is scarce, but is consistent with findings in adults. In contrast, there are studies which show that interventions aimed to improve weight loss and limit renal damage and proteinuria is reduced, the blood pressure and glomerular filtration rate. Allthe above make us think on the need to improve efforts to reduce the prevalence of obesity from the early stages of life, which could reduce the number of patients with CKD in the future. PMID- 27197110 TI - [Estrogen receptor alpha in obesity and diabetes]. AB - Estradiol (E2) is an important hormone in reproductive physiology, cardiovascular, skeletal and in the central nervous system (CNS). In human and rodents, E2 and its receptors are involved in the control of energy and glucose metabolism in health and metabolic diseases. The estrogen receptor (ER) belongs to the superfamily of nuclear receptors (NR), which are transcription factors that regulate gene expression. Three ER, ER-alpha, ER-beta and the G protein coupled ER (GPER; also called GPR30) in tissues are involved in glucose and lipid homeostasis. Also, it may have important implications for risk factors associated with metabolic syndrome (MS), insulin resistance (IR), obesity and type 2 diabetes (T2D). PMID- 27197111 TI - [Bacterial meningitis as first manifestation of a patient with multiple myeloma. A case report]. AB - BACKGROUND: Multiple myeloma (MM) is a plasma cell neoplasm characterized by clonal proliferation of plasma cells in the bone marrow and monoclonal protein in serum and/or urine in association to target organ damage. Infections are a frequent finding and they are multifactorial and presented mainly in the first months of diagnosis. CLINICAL CASE: We reported the case of a 62 years old woman, with impaired alertness, drowsiness, fever, incoherent speech and meningeal signs, cerebrospinal fluid showed polymorphonuclear pleocytosis, hypoglycorrhachia, hyperproteinorrhachia, and Gram positive cocci, she received antibiotic treatment and improved until resolution of symptoms, however when conscious she referred paraplegia and back pain, anemia, lymphopenia, elevation of serum globulins, calcium and CRP. The bone marrow aspiration showed infiltration by plasma cells and the serum protein electrophoresis and immunofixation showed the presence of monoclonal gamma IgA lambda spike. Smears of cerebrospinal fluid was absent of plasma cells. The diagnosis of multiple myeloma stage III-A is established. CONCLUSIONS: Association between (MM) and infection is high and although rare as first manifestation of MM, should take focus and high suspicion in patients with suggestive manifestations not explained by the infection itself. PMID- 27197113 TI - [Zika, a neurotropic virus?]. AB - In this paper, the neurotropism potential Zika virus is discussed, by comparison with viruses both RNA and DNA are neurotropic known, also it is said that compared with the new viruses that have affected the Americas, as the chikungunya, Zika has shown great affinity by brain tissue, manifested by a high incidence of acute neurological conditions, such as Guillain-Barre syndrome, among others, as well as the reported incidence of microcephaly that is abnormally high compared with the previous incidence, which, in a stillborn subject necropsied significant alterations demonstrated in brain tissue, identifying viral material and live virus in the fetoplacental complex, and demonstrating the impact both white matter and gray matter as well as basal ganglia, corpus callosum, ventricles and spinal cord, which could explain the microcephaly that concerns him. Although not a direct cause-effect relationship is demonstrated, however current evidence supports that relationship, hoping to be supported scientifically. PMID- 27197114 TI - Cathodic processes of neodymium(iii) in LiF-NdF3-Nd2O3 melts. AB - In this paper, cyclic voltammetry and square wave voltammetry are applied to characterize the cathode processes of neodymium ions on a W electrode in LiF-NdF3 melts with or without the metal Nd. The results indicate that neodymium ions in the LiF-NdF3 (2 wt%) melt are reduced in two steps, i.e. Nd(3+) -> Nd(2+) and Nd(2+) -> Nd(0), corresponding to starting reduction potentials of 0.35 V vs. Li(+)/Li and 0.1 V vs. Li(+)/Li, respectively. The Nd(3+) -> Nd(2+) process is controlled by mass transfer and the Nd(2+) -> Nd(0) process is controlled by both an interfacial step and mass transfer. But in the LiF-NdF3 melt with excess metal Nd equilibrium, the kinetics of the above two processes are controlled by mass transfer. After potentiostatic electrolysis at 0.35 V in the LiF-NdF3-Nd2O3 melt NdF2 is formed on the Mo cathode, and metallic Nd is obtained by potentiostatic electrolysis at 0.1 V in the LiF-NdF3-Nd2O3-Nd melt, which validates the above electrochemical reduction results. PMID- 27197112 TI - [Bouveret's syndrome: A rare presentation of gallstone ileus]. AB - BACKGROUND: Bouveret's syndrome is defined as gastric outlet obstruction caused by duodenal impaction of a gallstone which passes into the duodenal bulb through a cholecystoduodenal fistula. CLINICAL CASE: We reported the case of a 46-year old woman who presented intermittent epigastric pain, nausea, vomiting, and weight loss of 2-months duration. The patient admitted alcohol and methamphetamine abuse. She had not fever, dehydration or jaundice. Amylase, electrolytes, enzymes, and creatinine level were within normal limits. Seven months previously she was seen in the emergency department for acute cholecystitis. In that occasion, an abdominal ultrasound was reported with cholelithiasis without dilatation of the intra/extra-hepatic bile duct. Abdominal plain radiographs showed no relevant findings. A laparoscopic surgery was performed. During the procedure a sub-hepatic plastron with firm adhesions was found. The gallbladder was found attached to the duodenal bulb and an impacted calculus in the duodenum. The procedure was converted to surgery. Surgeon decided to perform a Bilroth 1 as the best choice. Seven days later, she was discharged. CONCLUSIONS: The clinical manifestations of the Bouveret's syndrome are nonspecific. Preoperative diagnosis is a challenge for clinicians because of the rarity of this condition. Treatment must be individualized. PMID- 27197115 TI - The Activity Profile of Elite Low-Kick Kickboxing Competition. AB - PURPOSE: To determine the performance aspects (time-motion and technical-tactical analysis) of top-level low-kick kickboxers according to gender, weight category, combat round, and match outcome. METHODS: Seventy-two kickboxers (44 male, 28 female) were studied. Thirty-six bouts (male = 61, female = 41 rounds) were analyzed using a time-motion system. Time structure was classified into 3 phases: preparatory-activity time (PT), fighting time (FT), and stoppage time (ST). RESULTS: Referee decisions caused an overall effort:pause ratio (E:P) of ~1:1.5, with a significant difference between weight categories (light and middleweights = 1:1.5, heavyweight = 1:1). This ratio was ~1:6 when high-intensity actions-to pause activities were considered. Significant differences were also observed between rounds (all P < .001), with 1st-, 2nd-, and 3rd-round E:Ps of 1:1, 1:1.5, and ~1:2, respectively. The relative times of FT and PT, total attacking actions, upper-limb actions, number of technical actions performed on the head, and the number of high-intensity actions were higher in males than females (all P = .05). Males performed more jab-cross actions and fewer low kicks than females (P < .001). Males used upper-limb (63.4%) more than lower-limb techniques (36.6%), targeting the head (56.9%) more than the body/leg (43.1%), with no significant difference from females (P > .05). E:P was similar between winners and losers. However, the numbers of technical actions performed on the head, counterattack actions, jab-cross technique, and total punches were higher in winners than losers (all P < .05). CONCLUSIONS: Training programs need to be adapted to the specific requirements of kickboxers' weight categories and gender to develop the technical-tactical abilities that improve athletes' chances of winning. PMID- 27197116 TI - Facial Nerve Reconstruction With Concurrent Masseteric Nerve Transfer and Cable Grafting. AB - IMPORTANCE: Reconstruction of the facial nerve after radical parotidectomy is commonly performed with cable grafting, which is associated with slow recovery of nerve function and synkinesis. OBJECTIVE: To describe facial nerve reconstruction after radical parotidectomy using concurrent masseteric nerve transfer and cable grafting. DESIGN, SETTING, AND PARTICIPANTS: This retrospective medical record review at a tertiary referral hospital included 9 patients who underwent concurrent masseteric nerve transfer and cable grafting for facial nerve reconstruction performed by a single surgeon from January 1, 2014, to October 31, 2015. Final follow-up was completed on March 14, 2016. MAIN OUTCOMES AND MEASURES: Improvement in resting facial symmetry and oral commissure excursion and synkinesis. RESULTS: Nine patients (6 women; mean age, 62.6 years; age range, 51-73 years) underwent immediate facial nerve reconstruction after radical parotidectomy using concurrent cable grafting and masseteric nerve transposition. All patients had return of oral commissure motion within 2 to 7 months after surgery with good excursion and minimal synkinesis. CONCLUSIONS AND RELEVANCE: Masseteric nerve transposition can be combined with cable grafting to improve outcomes in facial rehabilitation after radical parotidectomy. LEVEL OF EVIDENCE: 4. PMID- 27197117 TI - Omics approaches to probe markers of disease resistance in animal sciences. AB - Omics technologies have been developed in recent decades and used in different thematics. More advancements were done in human and plant thematics. Omics is the conjugation of different techniques, studying all biological molecules (DNA, RNA, proteins, metabolites, etc.). Omics is then able to study entire pathways, elucidating phenotypes and their control. Thus, thanks to Omics, it is possible to have a broad overview of the linkage between genotypes and phenotypes. Disease phenotypes (tolerance or resistance) are important to understand in both production and health. Nowadays a plethora of research articles are presenting results in the field of natural disease resistance of animals using Omics technologies. Moreover, thanks to advanced high throughput technologies novel modes of infections (infection pathways) are coming to the surface. Such pathways are complex (hundreds to thousands of molecules implied, with complicated control mechanisms), and Omics can generate useful knowledge to understand those pathways. Here we aim to review several angles of Omics used to probe markers of disease resistance with recent publications and data on the field, and present perspectives and its utilization for a better understanding of diseases. PMID- 27197118 TI - Repeated Sprints: An Independent Not Dependent Variable. AB - The ability to repeatedly perform sprints has traditionally been viewed as a key performance measure in team sports, and the relationship between repeated-sprint ability (RSA) and performance has been explored extensively. However, when reviewing the repeated-sprint profile of team-sports match play it appears that the occurrence of repeated-sprint bouts is sparse, indicating that RSA is not as important to performance as commonly believed. Repeated sprints are, however, a potent and time-efficient training strategy, effective in developing acceleration, speed, explosive leg power, aerobic power, and high-intensity running performance--all of which are crucial to team-sport performance. As such, we propose that repeated-sprint exercise in team sports should be viewed as an independent variable (eg, a means of developing fitness) as opposed to a dependent variable (eg, a means of assessing fitness/performance). PMID- 27197119 TI - Not All Mice Are the Same: Standardization of Animal Research Data Presentation. PMID- 27197120 TI - The Effect of Caffeine on Repeat-High-Intensity-Effort Performance in Rugby League Players. AB - CONTEXT: Repeat-high-intensity efforts (RHIEs) have recently been shown to occur at critical periods of rugby league matches. PURPOSE: To examine the effect that caffeine has on RHIE performance in rugby league players. METHODS: Using a double blind, placebo-controlled, crossover design, 11 semiprofessional rugby league players (age 19.0 +/- 0.5 y, body mass 87.4 +/- 12.9 kg, height 178.9 +/- 2.6 cm) completed 2 experimental trials that involved completing an RHIE test after either caffeine (300 mg caffeine) or placebo (vitamin H) ingestion. Each trial consisted of 3 sets of 20-m sprints interspersed with bouts of tackling. During the RHIE test, 20-m-sprint time, heart rate (HR), rating of perceived exertion (RPE), and blood lactate were measured. RESULTS: Total time to complete the nine 20-m sprints during the caffeine condition was 1.0% faster (28.46 +/- 1.4 s) than during the placebo condition (28.77 +/- 1.7 s) (ES = 0.18, 90%CI -0.7 to 0.1 s). This resulted in a very likely chance of caffeine being of benefit to RHIE performance (99% likely to be beneficial). These improvements were more pronounced in the early stages of the test, with a 1.3%, 1.0%, and 0.9% improvement in sprint performance during sets 1, 2, and 3 respectively. There was no significant difference in RPE across the 3 sets (P = .47, 0.48, 1.00) or mean HR (P = .36), maximal HR (P = .74), or blood lactate (P = .50) between treatment conditions. CONCLUSIONS: Preexercise ingestion of 300 mg caffeine produced practically meaningful improvements in RHIE performance in rugby league players. PMID- 27197121 TI - Endonasal (Closed) Rhinoplasty Technique: Securing Spreader Grafts With Barbed Suture. PMID- 27197122 TI - [Fundamental changes are needed in Icelandic healthcare[Editorial]]. PMID- 27197123 TI - [Can we reverse the ever increasing morbidity of food-allergy?[Editorial]]. PMID- 27197124 TI - [Chronic lymphocytic leukemia in Iceland from 2003 to 2013: Incidence, presentation and diagnosis]. AB - INTRODUCTION: Chronic lymphocytic leukemia (CLL) is characterized by the proliferation of monoclonal B-lymphocytes. MBL (monoclonal B-cell lymphocytosis) is considered a precursor state of the disease. Although CLL is incurable it is an indolent disorder and often detected incidentally on routine blood counts. Until now little information has been available on CLL in Iceland, including the incidence, diagnosis, symptoms or MBL precursor state. MATERIAL AND METHODS: This is a retrospective, descriptive study including CLL patients diagnosed in Iceland over the years 2003-2013. Registries of patients with a CLL diagnosis were obtained from the Icelandic Cancer Registry, Landspitali National University Hospital and the Medical Center in Mjodd. Medical records were reviewed for information on symptoms, diagnosis and treatment. Survival data and causes of death were obtained from national registries. RESULTS: The number of patients diagnosed with CLL over the study period was 161 (109 males, 52 females). The calculated incidence was 4.55/100,000, and the age-standardized incidence was 3.00/100,000. Mean age at diagnosis was 70.9 years (range 35-96 years). The Icelandic Cancer Registry lacked information on 28 patients (17.4%). The initial diagnosis of CLL was obtained exclusively with flow cytometry in 47.2% of cases. Symptoms were present at diagnosis in 67 of 151 patients (44.4%). One third of the group received chemotherapy and the average time to treatment was 1.3 years. Five-year survival was 70% and median survival was 9.4 years. Elevated lymphocyte counts (>=4,0x109/L) in peripheral blood prior (0.1 to 13.4 years) to diagnosis of CLL was identified in 85 of 99 CLL patients (85.9%). CONCLUSION: The incidence of CLL in Iceland is similar to other Western countries. The registration of CLL cases in the Icelandic Cancer Registry must be improved, especially in cases where diagnosis is based solely on flow cytometry. Elevated lymphocyte counts were present in a large proportion of cases prior to the diagnosis of CLL. KEY WORDS: Chronic lymphocytic leukemia, CLL, monoclonal B-cell lymphocytosis, MBL, incidence, diagnosis. Correspondence: Anna Margret Halldorsdottir, annamha@landspitali.is. PMID- 27197125 TI - [A Review and Recommendations of Evidence-Based Treatments for Pediatric Obsessive-Compulsive Disorder]. AB - Pediatric obsessive-compulsive disorder (OCD) is characterized by recurrent obsessions and compulsions. In this review we depict evidence-based treatments for pediatric OCD patients. We searched PubMed for relevant publications including randomized controlled trials, reviews, and expert guidelines. Substantial evidence for cognitive behavior therapy (CBT) and specific serotonin reuptake inhibitors (SSRIs) among treatment-naive patients shows that both treatments are effective. CBT is significantly more effective than SSRI based on head-to-head trials. The evidence for CBT- or SSRI-resistant patients is limited but indicates that CBT and SSRI are effective treatments for CBT non-responders while a combination of CBT and SSRI is the most effective treatment for SSRI non responders with no prior exposure to CBT. The current data support clinical guidelines indicating that when CBT expertise is present, one can successfully treat patients with CBT. CBT is also as effective as SSRI in non-responders after 14 weeks of CBT. The results did not indicate that combined treatment of CBT and SSRI is more effective than CBT delivered by experts. However, combined treatment is more effective than SSRI in SSRI non-responders. KEY WORDS: Obsessive compulsive disorder, children and adolescents, treatment, Cognitive behavior therapy, selective serotonin reuptake inhibitors, atypical antipsychotics, treatment-resistant, treatment-refractory. Correspondence: Gudmundur Skarphedinsson, gudmundur.skarphedinsson@r-bup.no. PMID- 27197127 TI - [Organ transplantation - a complex process[Editorial]]. PMID- 27197126 TI - [Superior canal dehiscence - Case report]. AB - Superior canal dehiscence is a rare syndrome. The symptoms consist of hearing loss, dizziness and autophonia. The patient can be cured with surgery. A 28 year old woman went to several doctors for several months due to diminished hearing, dizziness and autophonia. The symptoms got worse. A work-up led to the diagnosis of superior canal dehiscence in the left ear. She underwent surgery and her symptoms improved. A latency in diagnosis is expected as the syndrome is rare. It's important to think of superior canal dehiscence when patients complain of these symptoms. KEY WORDS: superior canal dehiscence, autophonia, dizziness, hearing deficit. Correspondence: Bryndis Baldvinsdottir, bryndisbaldvins@gmail.com. PMID- 27197128 TI - [Intoxication of power[Editorial]]. PMID- 27197129 TI - [Postnatal corticosteroids in preterm infants with immature lung disease]. AB - INTRODUCTION: Corticosteroids have been used in preterm infants with immature lungs to decrease their need for supplemental oxygen and mechanical ventilation. Whether the benefits of the treatment outweigh possible adverse effects remains controversial. The main objective of the study was to evaluate the effects of intravenous and inhalation corticosteroids on preterm infants' need for supplemental oxygen and mechanical ventilation and potential adverse effects. MATERIAL AND METHODS: This was a retrospective cohort study on preterm infants at the Neonatal Intensive Care Unit of Children's Hospital Iceland, born between 2000-2014 and treated with intravenous (n=28) or inhalation (n=30) corticosteroids for immature lung disease. For each infant receiving steriods one infant who did not receive steriods was selected as control, matched on gestational age. RESULTS: There was a significant decrease in the need for supplemental oxygen following intravenous and inhalation corticosteroids administration, and a significant decrease in the need for mechanical ventilation following intravenous corticosteroids administration, but not in controls. Infants receiving intravenous corticosteroids gained significantly less weight than controls during treatment, but no significant difference in weight between groups was found at 35 weeks postmenstrual age, or in other possible adverse effects such as the prevalence of cerebral palsy. CONCLUSION: Intravenous and inhalation corticosteroids decrease the need for supplemental oxygen in preterm infants with immature lung disease and intravenous steriods facilitate earlier weaning from mechanical ventilation, without significant adverse effects. Therefore, it seems justifiable in selected cases to use corticosteroids in treatment of preterm infants with severe immature lung disease. KEY WORDS: Corticosteroids, preterm infants, chronic lung disease, mechanical ventilation. Correspondence: Thordur Thorkelsson, thordth@landspitali.is. PMID- 27197130 TI - [Lung Transplantation in Icelanders]. AB - INTRODUCTION: Lung transplantation is a treatment option for end-stage lung diseases, excluding lung cancer, when life expectancy is short and quality of life is poor. In most instances pulmonary function and quality of life improves after lung transplantation. Infections and rejection are the most common complications and limit the feasibility of lung transplantation. MATERIALS AND METHODS: Retrospective analysis of lung transplantations performed on Icelanders from February 1988 to January 2015. Clinical information was obtained from medical records and a database was created. Information on demographics, underlying lung disease, type of transplantation, immunosuppression, rejection and other complications was collected. RESULTS: A total of 21 lung transplantations were performed, one of which was a retransplantation. There were 9 females and 11 males and the mean age was 45 years (20-61 years). Most of the operations were done at the Sahlgrenska hospital in Gothenburg. Bilateral lung transplantion was the most common operation. COPD was the most common indication. Rejection and infections were the most common complications. Eight of 20 patients have had acute rejection and half of the patients chronic rejection. Six of 20 patients are deceased, three died from chronic rejection. Median survival is 8,5 years. Five-year survival is 74%. CONCLUSIONS: Lung transplantations are currently performed at the Sahlgrenska hospital in Gothenburg but follow-up is in the hands of specialized pulmonologists in Iceland. Complications and survival for Icelandic patients is similar to larger centers. Close cooperation with the transplanting center is essential. KEY WORDS: lung transplantation, Icelanders, indications, survival, complications. PMID- 27197131 TI - [Demodex folliculorum a hidden cause of blepharitis]. AB - Meibomian gland dysfunction (MGD) is a common cause of dry eye disease. Demodex mites can cause MGD with symptoms like itching, dryness and general ocular discomfort. It is important to consider infestation with Demodex mites in individuals who are non responsive to traditional MGD treatment but also equally important when cylindrical dandruff is seen at the base of the eye lashes.. We report two individuals who had not responded to ocular and systemic treatment for MGD and were then diagnosed with Demodex mites. Treatment with BlephEx and Tea tree oil was successful. This is the first report on Demodex folliculorum in Iceland where a genetic analysis was done. KEY WORDS: Demodex, blepharitis, debris, tea tree oil, dry eye. Correspondence: Sigurlaug Gudrun Gunnarsdottir sigurlaug@sjonlag.is. PMID- 27197133 TI - Quality performance of laboratory testing in pharmacies: a collaborative evaluation. AB - BACKGROUND: The quality performance and the comparability between results of pharmacies point-of-care-testing (POCT) and institutional laboratories have been evaluated. METHODS: Eight pharmacies participated in the project: a capillary specimen collected by the pharmacist and, simultaneously, a lithium-heparin sample drawn by a physician of laboratory medicine for the pharmacy customers (n=106) were analyzed in the pharmacy and in the laboratory, respectively. Glucose, cholesterol, HDL-cholesterol, triglycerides, creatinine, uric acid, aspartate aminotransferase, alanine aminotransferase, were measured using: Reflotron, n=5; Samsung, n=1; Cardiocheck PA, n=1; Cholestech LDX, n=1 and Cobas 8000. The POCT analytical performance only (phase 2) were evaluated testing, in pharmacies and in the laboratory, the lithium heparin samples from a female drawn fasting daily in a week, and a control sample containing high concentrations of glucose, cholesterol and triglycerides. RESULTS: For all parameters, except triglycerides, the slopes showed a satisfactory correlation. For triglycerides, a median value higher in POCT in comparison to the laboratory (1.627 mmol/L vs. 0.950 mmol/L) has been observed. The agreement in the subjects classification, demonstrates that for glucose, 70% of the subjects show concentrations below the POCT recommended level (5.8-6.1 mmol/L), while 56% are according to the laboratory limit (<5.6 mmol/L). Total cholesterol exhibits a similar trend while POCT triglycerides show a greater percentage of increased values (21% vs. 9%). The reduction in triglycerides bias (phase 2) suggests that differences between POCT and central laboratory is attributable to a pre-analytical problem. CONCLUSIONS: The results confirm the acceptable analytical performance of POCT pharmacies and specific criticisms in the pre- and post-analytical phases. PMID- 27197132 TI - LC/ESI-MS/MS profiling of Ulmus parvifolia extracts and evaluation of its anti inflammatory, cytotoxic, and antioxidant activities. AB - In this study, a comparative liquid chromatography/mass spectroscopy (LC/ESI MS/MS) profiling of different fractions of Ulmus parvifolia leaves and stems was performed. Identification of compounds was based on comparing the mass spectrometric information obtained including m/z values and individual compound fragmentation pattern to tandem mass spectral library search and literature data. Eleven compounds were tentatively identified in the different analyzed fractions. One of the major constituents of this plant was isolated and identified as Icariside E4 [dihydro-dehydro-diconiferyl alcohol-4-O-alpha-L-rhamnopyranoside] (5). The evaluation of anti-inflammatory activity of the total methanolic extract using nitric oxide inhibition on LPS-stimulated RAW 264.7 cells model strong anti inflammatory activity with 17.5% inhibition of nitric oxide production versus 10% inhibition for dexamethasone. The cytotoxic activity of the methanolic extract and Icariside E4 was evaluated against four types of human cell lines using MTT assay. Icariside E4 showed cytotoxic effect against Hep-G2, MCF-7, and CACO-2 cell lines compared to a negligible activity for the total extract. The same extract showed a moderate antioxidant activity with SC50=362.5 MUg/mL. PMID- 27197135 TI - Measurement uncertainty - a revised understanding of its calculation and use. PMID- 27197134 TI - Optimal collection tubes for plasma glucose determination: confusion reigns supreme. PMID- 27197137 TI - The Effects of Residential Segregation and Neighborhood Characteristics on Surgery and Survival in Patients with Early-Stage Non-Small Cell Lung Cancer. AB - BACKGROUND: Although the negative effects of lower socioeconomic status on non small cell lung cancer (NSCLC) treatment and survival have been widely studied, the impact of residential segregation on prognosis and the receipt of treatment has yet to be determined. METHODS: This is a retrospective, cohort study of NSCLC patients in Georgia (2000-2009; n = 8,322) using data from the Georgia Comprehensive Cancer Registry. The effects of segregation, economic deprivation, and combined segregation/deprivation on the odds of receiving surgery were examined in separate multilevel models. To determine the association for the exposures of interest on the risk of death for different racial groups, separate multilevel survival models were conducted for black and white patients. RESULTS: Living in areas with the highest [AOR = 0.35, 95% confidence interval (CI), 0.19 0.64] and second highest (AOR = 0.37, 95% CI, 0.20-0.68) levels of segregation was associated with decreased odds of receipt of surgery. Black patients living in areas with high residential segregation and high economic deprivation were 31% (95% CI, 1.04-1.66) more likely to die, even after surgery was controlled for. For white patients, economic deprivation was associated with decreased odds of surgery but not survival. Segregation had no effect. CONCLUSION: Our findings suggest how black and white individuals experience segregation and area-level poverty is likely different leading to differences in adverse health outcomes. IMPACT: Identifying neighborhood characteristics impacting health outcomes within different racial groups could help reduce health disparities across racial groups by implementing targeted policies and interventions. Cancer Epidemiol Biomarkers Prev; 25(5); 750-8. (c)2016 AACR. PMID- 27197139 TI - Periodontal Disease and Breast Cancer-Letter. PMID- 27197138 TI - Cancer Mortality Risks from Long-term Exposure to Ambient Fine Particle. AB - BACKGROUND: Few studies have assessed long-term effects of particulate matter (PM) with aerodynamic diameter < 2.5 MUm (PM2.5) on mortality for causes of cancer other than the lung; we assessed the effects on multiple causes. In Hong Kong, most people live and work in urban or suburban areas with high-rise buildings. This facilitates the estimation of PM2.5 exposure of individuals, taking into account the height of residence above ground level for assessment of the long-term health effects with sufficient statistical power. METHODS: We recruited 66,820 persons who were >=65 in 1998 to 2001 and followed up for mortality outcomes until 2011. Annual concentrations of PM at their residential addresses were estimated using PM2.5 concentrations measured at fixed-site monitors, horizontal-vertical locations, and satellite data. We used Cox regression model to assess the HR of mortality for cancer per 10 MUg/m(3) increase of PM2.5 RESULTS: PM2.5 was associated with increased risk of mortality for all causes of cancer [HR, 1.22 (95% CI, 1.11-1.34)] and for specific cause of cancer in upper digestive tract [1.42 (1.06-1.89)], digestive accessory organs [1.35 (1.06-1.71)] in all subjects; breast [1.80 (1.26-2.55)] in females; and lung [1.36 (1.05-1.77)] in males. CONCLUSIONS: Long-term exposures to PM2.5 are associated with elevated risks of cancer in various organs. IMPACT: This study is particularly timely in China, where compelling evidence is needed to support the pollution control policy to ameliorate the health damages associated with economic growth. Cancer Epidemiol Biomarkers Prev; 25(5); 839-45. (c)2016 AACR. PMID- 27197140 TI - Periodontal Disease and Breast Cancer-Response. PMID- 27197141 TI - Periodontal Disease and Breast Cancer-Letter. PMID- 27197142 TI - Periodontal Disease and Breast Cancer-Response. PMID- 27197143 TI - Quality of Physician Communication about HPV Vaccine-Letter. PMID- 27197145 TI - Impact of Screening on Breast Cancer Mortality-Letter. PMID- 27197144 TI - Quality of Physician Communication about HPV Vaccine-Response. PMID- 27197146 TI - Impact of Screening on Breast Cancer Mortality-Response. PMID- 27197147 TI - Comparative Cistromics Reveals Genomic Cross-talk between FOXA1 and ERalpha in Tamoxifen-Associated Endometrial Carcinomas. AB - Tamoxifen, a small-molecule antagonist of the transcription factor estrogen receptor alpha (ERalpha) used to treat breast cancer, increases risks of endometrial cancer. However, no parallels of ERalpha transcriptional action in breast and endometrial tumors have been found that might explain this effect. In this study, we addressed this issue with a genome-wide assessment of ERalpha chromatin interactions in surgical specimens obtained from patients with tamoxifen-associated endometrial cancer. ERalpha was found at active enhancers in endometrial cancer cells as marked by the presence of RNA polymerase II and the histone marker H3K27Ac. These ERalpha binding sites were highly conserved between breast and endometrial cancer and enriched in binding motifs for the transcription factor FOXA1, which displayed substantial overlap with ERalpha binding sites proximal to genes involved in classical ERalpha target genes. Multifactorial ChIP-seq data integration from the endometrial cancer cell line Ishikawa illustrated a functional genomic network involving ERalpha and FOXA1 together with the enhancer-enriched transcriptional regulators p300, FOXM1, TEAD4, FNFIC, CEBP8, and TCF12. Immunohistochemical analysis of 230 primary endometrial tumor specimens showed that lack of FOXA1 and ERalpha expression was associated with a longer interval between breast cancer and the emergence of endometrial cancer, exclusively in tamoxifen-treated patients. Our results define conserved sites for a genomic interplay between FOXA1 and ERalpha in breast cancer and tamoxifen-associated endometrial cancer. In addition, FOXA1 and ERalpha are associated with the interval time between breast cancer and endometrial cancer only in tamoxifen-treated breast cancer patients. Cancer Res; 76(13); 3773-84. (c)2016 AACR. PMID- 27197148 TI - Cell Cycle-Dependent Mechanisms Underlie Vincristine-Induced Death of Primary Acute Lymphoblastic Leukemia Cells. AB - Microtubule-targeting agents (MTA), such as the taxanes and vinca alkaloids, are used to treat a variety of cancers due to their ability to perturb microtubule dynamics. In cell culture, MTAs exert their anticancer effects primarily by causing mitotic arrest and cell death. However, accumulating indirect evidence suggests that MTAs may exert their cytotoxicity in human tumors by interfering with interphase microtubules. In this study, we sought to develop and characterize an experimental system in which to test the hypothesis that MTAs induce cell death during interphase. Primary adult acute lymphoblastic leukemia (ALL) cells treated with vincristine only weakly exhibited colocalization between mitotic and apoptotic markers and major characteristics of mitotic death, such as an increase in cells with 4N DNA content before the appearance of cells with <2N DNA content, suggesting a mixed response. Therefore, we separated ALL cells into distinct phases of the cell cycle by centrifugal elutriation, labeled cells with 5-ethynyl-2'-deoxyuridine (EdU), and then treated each population with vincristine. Cells isolated during G1 underwent cell death without evidence of EdU uptake, indicating that the cytotoxic effects of vincristine took place during G1 Conversely, cells isolated during S or G2-M phases underwent death following mitotic arrest. Thus, vincristine induces distinct death programs in primary ALL cells depending on cell-cycle phase, and cells in G1 are particularly susceptible to perturbation of interphase microtubules. Primary ALL cells may therefore provide a powerful model system in which to study the multimodal mechanisms underlying MTA-induced cell death. Cancer Res; 76(12); 3553-61. (c)2016 AACR. PMID- 27197149 TI - In Situ Tumor Vaccination by Combining Local Radiation and Tumor-Specific Antibody or Immunocytokine Treatments. AB - Interest in combining radiotherapy and immune checkpoint therapy is growing rapidly. In this study, we explored a novel combination of this type to augment antitumor immune responses in preclinical murine models of melanoma, neuroblastoma, and head and neck squamous cell carcinoma. Cooperative effects were observed with local radiotherapy and intratumoral injection of tumor specific antibodies, arising in part from enhanced antibody-dependent cell mediated cytotoxicity (ADCC). We could improve this response by combining radiation with intratumoral injection of an IL2-linked tumor-specific antibody (termed here an immunocytokine), resulting in complete regression of established tumors in most animals associated with a tumor-specific memory T-cell response. Given the T-cell response elicited by combined local radiation and intratumoral immunocytokine, we tested the potential benefit of adding this treatment to immune checkpoint blockade. In mice bearing large primary tumors or disseminated metastases, the triple-combination of intratumoral immunocytokine, radiation, and systemic anti-CTLA-4 improved primary tumor response and animal survival compared with combinations of any two of these three interventions. Taken together, our results show how combining radiation and intratumoral immunocytokine in murine tumor models can eradicate large tumors and metastases, eliciting an in situ vaccination effect that can be leveraged further by T-cell checkpoint blockade, with immediate implications for clinical evaluation. Cancer Res; 76(13); 3929-41. (c)2016 AACR. PMID- 27197150 TI - Novel Protein Disulfide Isomerase Inhibitor with Anticancer Activity in Multiple Myeloma. AB - Multiple myeloma cells secrete more disulfide bond-rich proteins than any other mammalian cell. Thus, inhibition of protein disulfide isomerases (PDI) required for protein folding in the endoplasmic reticulum (ER) should increase ER stress beyond repair in this incurable cancer. Here, we report the mechanistically unbiased discovery of a novel PDI-inhibiting compound with antimyeloma activity. We screened a 30,355 small-molecule library using a multilayered multiple myeloma cell-based cytotoxicity assay that modeled disease niche, normal liver, kidney, and bone marrow. CCF642, a bone marrow-sparing compound, exhibited a submicromolar IC50 in 10 of 10 multiple myeloma cell lines. An active biotinylated analog of CCF642 defined binding to the PDI isoenzymes A1, A3, and A4 in MM cells. In vitro, CCF642 inhibited PDI reductase activity about 100-fold more potently than the structurally distinct established inhibitors PACMA 31 and LOC14. Computational modeling suggested a novel covalent binding mode in active site CGHCK motifs. Remarkably, without any further chemistry optimization, CCF642 displayed potent efficacy in an aggressive syngeneic mouse model of multiple myeloma and prolonged the lifespan of C57BL/KaLwRij mice engrafted with 5TGM1-luc myeloma, an effect comparable to the first-line multiple myeloma therapeutic bortezomib. Consistent with PDI inhibition, CCF642 caused acute ER stress in multiple myeloma cells accompanied by apoptosis-inducing calcium release. Overall, our results provide an illustration of the utility of simple in vivo simulations as part of a drug discovery effort, along with a sound preclinical rationale to develop a new small-molecule therapeutic to treat multiple myeloma. Cancer Res; 76(11); 3340-50. (c)2016 AACR. PMID- 27197151 TI - Decreased Expression of Fructose-1,6-bisphosphatase Associates with Glucose Metabolism and Tumor Progression in Hepatocellular Carcinoma. AB - Fructose-1,6-bisphosphatase (FBP1), the rate-limiting enzyme in gluconeogenesis, is reduced in expression in certain cancers where it has been hypothesized to act as a tumor suppressor, including in hepatocellular carcinoma (HCC). Here, we report functional evidence supporting this hypothesis, providing a preclinical rationale to develop FBP1 as a therapeutic target for HCC treatment. Three independent cohorts totaling 594 cases of HCC were analyzed to address clinical significance. Lower FBP1 expression associated with advanced tumor stage, poor overall survival, and higher tumor recurrence rates. In HCC cell lines, where endogenous FBP1 expression is low, engineering its ectopic overexpression inhibited tumor growth and intracellular glucose uptake by reducing aerobic glycolysis. In patient specimens, promoter methylation and copy-number loss of FBP1 were independently associated with decreased FBP1 expression. Similarly, FBP1 downregulation in HCC cell lines was also associated with copy-number loss. HCC specimens exhibiting low expression of FBP1 had a highly malignant phenotype, including large tumor size, poor differentiation, impaired gluconeogenesis, and enhanced aerobic glycolysis. The effects of FBP1 expression on prognosis and glucose metabolism were confirmed by gene set enrichment analysis. Overall, our findings established that FBP1 downregulation in HCC contributed to tumor progression and poor prognosis by altering glucose metabolism, and they rationalize further study of FBP1 as a prognostic biomarker and therapeutic target in HCC patients. Cancer Res; 76(11); 3265-76. (c)2016 AACR. PMID- 27197152 TI - Myeloid-Derived Suppressor Cells Endow Stem-like Qualities to Breast Cancer Cells through IL6/STAT3 and NO/NOTCH Cross-talk Signaling. AB - Myeloid-derived suppressor cells (MDSC) contribute to immune suppression in cancer, but the mechanisms through which they drive metastatic progression are not fully understood. In this study, we show how MDSC convey stem-like qualities to breast cancer cells that coordinately help enable immune suppression and escape. We found that MDSC promoted tumor formation by enhancing breast cancer cell stem-like properties as well as by suppressing T-cell activation. Mechanistic investigations indicated that these effects relied upon cross-talk between the STAT3 and NOTCH pathways in cancer cells, with MDSC inducing IL6 dependent phosphorylation of STAT3 and activating NOTCH through nitric oxide leading to prolonged STAT3 activation. In clinical specimens of breast cancer, the presence of MDSC correlated with the presence of cancer stem-like cells (CSC) and independently predicted poor survival outcomes. Collectively, our work revealed an immune-associated mechanism that extrinsically confers cancer cell stemness properties and affects patient outcome. We suggest that targeting STAT3 NOTCH cross-talk between MDSC and CSC could offer a unique locus to improve cancer treatment, by coordinately targeting a coupled mechanism that enables cancer stemness and immune escape. Cancer Res; 76(11); 3156-65. (c)2016 AACR. PMID- 27197153 TI - Guidance Molecule SEMA3A Restricts Tumor Growth by Differentially Regulating the Proliferation of Tumor-Associated Macrophages. AB - Accumulation of tumor-associated macrophages (TAM) correlates with malignant progression, immune suppression, and poor prognosis. In this study, we defined a critical role for the cell-surface guidance molecule SEMA3A in differential proliferative control of TAMs. Tumor cell-derived SEMA3A restricted the proliferation of protumoral M2 macrophages but increased the proliferation of antitumoral M1, acting through the SEMA3A receptor neuropilin 1. Expansion of M1 macrophages in vivo enhanced the recruitment and activation of natural killer (NK) cells and cytotoxic CD8(+) T cells to tumors, inhibiting their growth. In human breast cancer specimens, we found that immunohistochemical levels of SEMA3A correlated with the expression of genes characteristic of M1 macrophages, CD8(+) T cells, and NK cells, while inversely correlating with established characters of malignancy. In summary, our results illuminate a mechanism whereby the TAM phenotype is controlled and identify the cell-surface molecule SEMA3A as a candidate for therapeutic targeting. Cancer Res; 76(11); 3166-78. (c)2016 AACR. PMID- 27197155 TI - Oncogenic Mutation of AIMP2/p38 Inhibits Its Tumor-Suppressive Interaction with Smurf2. AB - AIMP2/p38 is a multifunctional tumor suppressor that normally resides in the cytosol as a scaffold protein of the multi-tRNA synthetase complex (MSC). One of the tumor-suppressive functions of AIMP2 is to facilitate ubiquitin-mediated degradation of FUSE-binding protein (FBP, FUBP1), a transcriptional activator of c-Myc. However, the mechanism by which AIMP2 functions within this pathway and its significance in tumorigenesis are uncertain. Here, we report that Smurf2 is responsible for AIMP2-mediated ubiquitination of FBP, and a mutation in AIMP2 that inhibited its nuclear interaction with Smurf2 enhanced cellular transformation and tumorigenesis in vivo Treatment of HeLa cells with TGFbeta resulted in the phosphorylation of AIMP2 on S156, a residue that is exposed on the embedded GST domain of AIMP2. We further found that phospho-AIMP2 dissociated from the MSC and translocated to the nucleus, where it bound to Smurf2, enhancing ubiquitination of FBP. AIMP2 also inhibited nuclear export of Smurf2 to sustain TGFbeta signaling. Collectively, these findings present a novel tumor-suppressive interaction between AIMP2 and Smurf2 and suggest that the disruption of this interaction can lead to oncogenic transformation. Cancer Res; 76(11); 3422-36. (c)2016 AACR. PMID- 27197157 TI - Molecular Insights of Pathways Resulting from Two Common PIK3CA Mutations in Breast Cancer. AB - The PI3K pathway is activated in approximately 70% of breast cancers. PIK3CA gene mutations or amplifications that affect the PI3K p110alpha subunit account for activation of this pathway in 20% to 40% of cases, particularly in estrogen receptor alpha (ERalpha)-positive breast cancers. AKT family of kinases, AKT1-3, are the downstream targets of PI3K and these kinases activate ERalpha. Although several inhibitors of PI3K have been developed, none has proven effective in the clinic, partly due to an incomplete understanding of the selective routing of PI3K signaling to specific AKT isoforms. Accordingly, we investigated in this study the contribution of specific AKT isoforms in connecting PI3K activation to ERalpha signaling, and we also assessed the utility of using the components of PI3K-AKT isoform-ERalpha signaling axis as predictive biomarkers of response to PI3K inhibitors. Using a variety of physiologically relevant model systems with defined natural or knock-in PIK3CA mutations and/or PI3K hyperactivation, we show that PIK3CA-E545K mutations (found in ~20% of PIK3CA-mutant breast cancers), but not PIK3CA-H1047R mutations (found in 55% of PIK3CA-mutant breast cancers), preferentially activate AKT1. Our findings argue that AKT1 signaling is needed to respond to estrogen and PI3K inhibitors in breast cancer cells with PIK3CA-E545K mutation, but not in breast cancer cells with other PIK3CA mutations. This study offers evidence that personalizing treatment of ER-positive breast cancers to PI3K inhibitor therapy may benefit from an analysis of PIK3CA-E545K-AKT1-estrogen signaling pathways. Cancer Res; 76(13); 3989-4001. (c)2016 AACR. PMID- 27197156 TI - Exome-Scale Discovery of Hotspot Mutation Regions in Human Cancer Using 3D Protein Structure. AB - The impact of somatic missense mutation on cancer etiology and progression is often difficult to interpret. One common approach for assessing the contribution of missense mutations in carcinogenesis is to identify genes mutated with statistically nonrandom frequencies. Even given the large number of sequenced cancer samples currently available, this approach remains underpowered to detect drivers, particularly in less studied cancer types. Alternative statistical and bioinformatic approaches are needed. One approach to increase power is to focus on localized regions of increased missense mutation density or hotspot regions, rather than a whole gene or protein domain. Detecting missense mutation hotspot regions in three-dimensional (3D) protein structure may also be beneficial because linear sequence alone does not fully describe the biologically relevant organization of codons. Here, we present a novel and statistically rigorous algorithm for detecting missense mutation hotspot regions in 3D protein structures. We analyzed approximately 3 * 10(5) mutations from The Cancer Genome Atlas (TCGA) and identified 216 tumor-type-specific hotspot regions. In addition to experimentally determined protein structures, we considered high-quality structural models, which increase genomic coverage from approximately 5,000 to more than 15,000 genes. We provide new evidence that 3D mutation analysis has unique advantages. It enables discovery of hotspot regions in many more genes than previously shown and increases sensitivity to hotspot regions in tumor suppressor genes (TSG). Although hotspot regions have long been known to exist in both TSGs and oncogenes, we provide the first report that they have different characteristic properties in the two types of driver genes. We show how cancer researchers can use our results to link 3D protein structure and the biologic functions of missense mutations in cancer, and to generate testable hypotheses about driver mechanisms. Our results are included in a new interactive website for visualizing protein structures with TCGA mutations and associated hotspot regions. Users can submit new sequence data, facilitating the visualization of mutations in a biologically relevant context. Cancer Res; 76(13); 3719-31. (c)2016 AACR. PMID- 27197154 TI - Lenalidomide Stabilizes the Erythropoietin Receptor by Inhibiting the E3 Ubiquitin Ligase RNF41. AB - In a subset of patients with non-del(5q) myelodysplastic syndrome (MDS), lenalidomide promotes erythroid lineage competence and effective erythropoiesis. To determine the mechanism by which lenalidomide promotes erythropoiesis, we investigated its action on erythropoietin receptor (EpoR) cellular dynamics. Lenalidomide upregulated expression and stability of JAK2-associated EpoR in UT7 erythroid cells and primary CD71+ erythroid progenitors. The effects of lenalidomide on receptor turnover were Type I cytokine receptor specific, as evidenced by coregulation of the IL3-Ralpha receptor but not c-Kit. To elucidate this mechanism, we investigated the effects of lenalidomide on the E3 ubiquitin ligase RNF41. Lenalidomide promoted EpoR/RNF41 association and inhibited RNF41 auto-ubiquitination, accompanied by a reduction in EpoR ubiquitination. To confirm that RNF41 is the principal target responsible for EpoR stabilization, HEK293T cells were transfected with EpoR and/or RNF41 gene expression vectors. Steady-state EpoR expression was reduced in EpoR/RNF41 cells, whereas EpoR upregulation by lenalidomide was abrogated, indicating that cellular RNF41 is a critical determinant of drug-induced receptor modulation. Notably, shRNA suppression of CRBN gene expression failed to alter EpoR upregulation, indicating that drug-induced receptor modulation is independent of cereblon. Immunohistochemical staining showed that RNF41 expression decreased in primary erythroid cells of lenalidomide-responding patients, suggesting that cellular RNF41 expression merits investigation as a biomarker for lenalidomide response. Our findings indicate that lenalidomide has E3 ubiquitin ligase inhibitory effects that extend to RNF41 and that inhibition of RNF41 auto-ubiquitination promotes membrane accumulation of signaling competent JAK2/EpoR complexes that augment Epo responsiveness. Cancer Res; 76(12); 3531-40. (c)2016 AACR. PMID- 27197158 TI - Rictor/mTORC2 Drives Progression and Therapeutic Resistance of HER2-Amplified Breast Cancers. AB - HER2 overexpression drives Akt signaling and cell survival and HER2-enriched breast tumors have a poor outcome when Akt is upregulated. Akt is activated by phosphorylation at T308 via PI3K and S473 via mTORC2. The importance of PI3K activated Akt signaling is well documented in HER2-amplified breast cancer models, but the significance of mTORC2-activated Akt signaling in this setting remains uncertain. We report here that the mTORC2 obligate cofactor Rictor is enriched in HER2-amplified samples, correlating with increased phosphorylation at S473 on Akt. In invasive breast cancer specimens, Rictor expression was upregulated significantly compared with nonmalignant tissues. In a HER2/Neu mouse model of breast cancer, genetic ablation of Rictor decreased cell survival and phosphorylation at S473 on Akt, delaying tumor latency, penetrance, and burden. In HER2-amplified cells, exposure to an mTORC1/2 dual kinase inhibitor decreased Akt-dependent cell survival, including in cells resistant to lapatinib, where cytotoxicity could be restored. We replicated these findings by silencing Rictor in breast cancer cell lines, but not silencing the mTORC1 cofactor Raptor (RPTOR). Taken together, our findings establish that Rictor/mTORC2 signaling drives Akt-dependent tumor progression in HER2-amplified breast cancers, rationalizing clinical investigation of dual mTORC1/2 kinase inhibitors and developing mTORC2-specific inhibitors for use in this setting. Cancer Res; 76(16); 4752-64. (c)2016 AACR. PMID- 27197159 TI - Decreased Mitochondrial Mutagenesis during Transformation of Human Breast Stem Cells into Tumorigenic Cells. AB - Rare stochastic mutations may accumulate during dormancy of stem-like cells, but technical limitations in DNA sequencing have limited exploring this possibility. In this study, we employed a recently established deep-sequencing method termed Duplex Sequencing to conduct a genome-wide analysis of mitochondrial (mt) DNA mutations in a human breast stem cell model that recapitulates the sequential stages of breast carcinogenesis. Using this method, we found significant differences in mtDNA among normal stem cells, immortal/preneoplastic cells, and tumorigenic cells. Putative cancer stem-like cell (CSC) populations and mtDNA copy numbers increased as normal stem cells become tumorigenic cells. Transformed cells exhibited lower rare mutation frequencies of whole mtDNA than did normal stem cells. The predicted mtDNA rare mutation pathogenicity was significantly lower in tumorigenic cells than normal stem cells. Major rare mutation types in normal stem cells are C>T/G>A and T>C/A>G transitions, while only C>T/G>A are major types in transformed cells. We detected a total of 1,220 rare point mutations, 678 of which were unreported previously. With only one possible exception (m10342T>C), we did not find specific mutations characterizing mtDNA in human breast CSCs; rather, the mitochondrial genome of CSCs displayed an overall decrease in rare mutations. On the basis of our work, we suggest that this decrease (in particular T>C/A>G transitions), rather than the presence of specific mitochondrial mutations, may constitute an early biomarker for breast cancer detection. Our findings support the hypothesis that the mitochondrial genome is altered greatly as a result of the transformation of normal stem cells to CSCs, and that mtDNA mutation signatures may aid in delineating normal stem cells from CSCs. Cancer Res; 76(15); 4569-78. (c)2016 AACR. PMID- 27197160 TI - Disrupting Hypoxia-Induced Bicarbonate Transport Acidifies Tumor Cells and Suppresses Tumor Growth. AB - Tumor hypoxia is associated clinically with therapeutic resistance and poor patient outcomes. One feature of tumor hypoxia is activated expression of carbonic anhydrase IX (CA9), a regulator of pH and tumor growth. In this study, we investigated the hypothesis that impeding the reuptake of bicarbonate produced extracellularly by CA9 could exacerbate the intracellular acidity produced by hypoxic conditions, perhaps compromising cell growth and viability as a result. In 8 of 10 cancer cell lines, we found that hypoxia induced the expression of at least one bicarbonate transporter. The most robust and frequent inductions were of the sodium-driven bicarbonate transporters SLC4A4 and SLC4A9, which rely upon both HIF1alpha and HIF2alpha activity for their expression. In cancer cell spheroids, SLC4A4 or SLC4A9 disruption by either genetic or pharmaceutical approaches acidified intracellular pH and reduced cell growth. Furthermore, treatment of spheroids with S0859, a small-molecule inhibitor of sodium-driven bicarbonate transporters, increased apoptosis in the cell lines tested. Finally, RNAi-mediated attenuation of SLC4A9 increased apoptosis in MDA-MB-231 breast cancer spheroids and dramatically reduced growth of MDA-MB-231 breast tumors or U87 gliomas in murine xenografts. Our findings suggest that disrupting pH homeostasis by blocking bicarbonate import might broadly relieve the common resistance of hypoxic tumors to anticancer therapy. Cancer Res; 76(13); 3744-55. (c)2016 AACR. PMID- 27197161 TI - Downregulation of the TGFbeta Pseudoreceptor BAMBI in Non-Small Cell Lung Cancer Enhances TGFbeta Signaling and Invasion. AB - Non-small cell lung cancer (NSCLC) is characterized by early metastasis and has the highest mortality rate among all solid tumors, with the majority of patients diagnosed at an advanced stage where curative therapeutic options are lacking. In this study, we identify a targetable mechanism involving TGFbeta elevation that orchestrates tumor progression in this disease. Substantial activation of this pathway was detected in human lung cancer tissues with concomitant downregulation of BAMBI, a negative regulator of the TGFbeta signaling pathway. Alterations of epithelial-to-mesenchymal transition (EMT) marker expression were observed in lung cancer samples compared with tumor-free tissues. Distinct alterations in the DNA methylation of the gene regions encoding TGFbeta pathway components were detected in NSCLC samples compared with tumor-free lung tissues. In particular, epigenetic silencing of BAMBI was identified as a hallmark of NSCLC. Reconstitution of BAMBI expression in NSCLC cells resulted in a marked reduction of TGFbeta-induced EMT, migration, and invasion in vitro, along with reduced tumor burden and tumor growth in vivo In conclusion, our results demonstrate how BAMBI downregulation drives the invasiveness of NSCLC, highlighting TGFbeta signaling as a candidate therapeutic target in this setting. Cancer Res; 76(13); 3785-801. (c)2016 AACR. PMID- 27197162 TI - Endothelial Side Population Cells Contribute to Tumor Angiogenesis and Antiangiogenic Drug Resistance. AB - Angiogenesis plays a crucial role in tumor growth, with an undisputed contribution of resident endothelial cells (EC) to new blood vessels in the tumor. Here, we report the definition of a small population of vascular-resident stem/progenitor-like EC that contributes predominantly to new blood vessel formation in the tumor. Although the surface markers of this population are similar to other ECs, those from the lung vasculature possess colony-forming ability in vitro and contribute to angiogenesis in vivo These specific ECs actively proliferate in lung tumors, and the percentage of this population significantly increases in the tumor vasculature relative to normal lung tissue. Using genetic recombination and bone marrow transplant models, we show that these cells are phenotypically true ECs and do not originate from hematopoietic cells. After treatment of tumors with antiangiogenic drugs, these specific ECs selectively survived and remained in the tumor. Together, our results established that ECs in the peripheral vasculature are heterogeneous and that stem/progenitor like ECs play an indispensable role in tumor angiogenesis as EC-supplying cells. The lack of susceptibility of these ECs to antiangiogenic drugs may account for resistance of the tumor to this drug type. Thus, inhibiting these ECs might provide a promising strategy to overcome antiangiogenic drug resistance. Cancer Res; 76(11); 3200-10. (c)2016 AACR. PMID- 27197163 TI - Impact of Pattern Recognition Receptors on the Prognosis of Breast Cancer Patients Undergoing Adjuvant Chemotherapy. AB - Pattern recognition receptors allow the innate immune system to perceive the presence of microbial products and to launch the first steps of the defense response. Some pattern recognition receptors also sense endogenous ligands that are released from uninfected dying cells, thereby activating immune responses against dead-cell antigens. This applies to toll-like receptors 3 and 4 (TLR3, TLR4), which sense double-stranded RNA and high-mobility group protein B1 (HMGB1), respectively, as well as to formyl peptide receptor-1 (FPR1), which interacts with Annexin A1 (ANXA1) from dead cells. Breast cancer patients who bear loss-of-function alleles in TLR3, TLR4, and FPR1 exhibit a reduced metastasis-free and overall survival after treatment with anthracycline-based adjuvant chemotherapy. These genetic defects are epistatic with respect to each other, suggesting that they act on the same pathway, linking chemotherapy to a therapeutically relevant anticancer immune response. Loss-of-function alleles in TLR4 and FPR1 also affect the prognosis of colorectal cancer patients treated with oxaliplatin-based chemotherapy. Altogether, these results support the idea that conventional anticancer treatments rely on stimulation of anticancer immune responses to become fully efficient. Cancer Res; 76(11); 3122-6. (c)2016 AACR. PMID- 27197164 TI - Toward Value-Based Pricing to Boost Cancer Research and Innovation. AB - The high market price of new anticancer agents has stimulated debate about the long-term sustainability of healthcare systems and whether these new agents can continue to be supported by public healthcare or by private insurers. In addition, some drugs have been approved with limited clinical benefit, raising concerns about setting a minimum requirement for medical benefit. Options to resolve these problems include raising the bar for approval of new drugs and/or pricing of new agents based on the medical benefit that they offer to patients. In this commentary, we suggest that new agents should be marketed in a two-step process that would include first the approval of the new drug by the regulatory agencies and second the introduction of a market price based on the medical benefit that the new intervention offers to patients. Introduction of value-based pricing would maintain the sustainability of health care systems and would improve drug development, as it would pressure pharmaceutical companies to become more innovative and avoid the development of compounds with limited benefit. Value-based pricing could also stimulate the funding of research directed to development of new anticancer drugs with novel mechanisms of action. Cancer Res; 76(11); 3127-9. (c)2016 AACR. PMID- 27197165 TI - Identification of MYC-Dependent Transcriptional Programs in Oncogene-Addicted Liver Tumors. AB - Tumors driven by activation of the transcription factor MYC generally show oncogene addiction. However, the gene expression programs that depend upon sustained MYC activity remain unknown. In this study, we employed a mouse model of liver carcinoma driven by a reversible tet-MYC transgene, combined with chromatin immunoprecipitation and gene expression profiling to identify MYC dependent regulatory events. As previously reported, MYC-expressing mice exhibited hepatoblastoma- and hepatocellular carcinoma-like tumors, which regressed when MYC expression was suppressed. We further show that cellular transformation, and thus initiation of liver tumorigenesis, were impaired in mice harboring a MYC mutant unable to associate with the corepressor protein MIZ1 (ZBTB17). Notably, switching off the oncogene in advanced carcinomas revealed that MYC was required for the continuous activation and repression of distinct sets of genes, constituting no more than half of all genes deregulated during tumor progression and an even smaller subset of all MYC-bound genes. Altogether, our data provide the first detailed analysis of a MYC-dependent transcriptional program in a fully developed carcinoma and offer a guide to identifying the critical effectors contributing to MYC-driven tumor maintenance. Cancer Res; 76(12); 3463-72. (c)2016 AACR. PMID- 27197166 TI - Radiation Sensitivity in a Preclinical Mouse Model of Medulloblastoma Relies on the Function of the Intrinsic Apoptotic Pathway. AB - While treatments that induce DNA damage are commonly used as anticancer therapies, the mechanisms through which DNA damage produces a therapeutic response are incompletely understood. Here we have tested whether medulloblastomas must be competent for apoptosis to be sensitive to radiotherapy. Whether apoptosis is required for radiation sensitivity has been controversial. Medulloblastoma, the most common malignant brain tumor in children, is a biologically heterogeneous set of tumors typically sensitive to radiation and chemotherapy; 80% of medulloblastoma patients survive long-term after treatment. We used functional genetic studies to determine whether the intrinsic apoptotic pathway is required for radiation to produce a therapeutic response in mice with primary, Shh-driven medulloblastoma. We found that cranial radiation extended the survival of medulloblastoma-bearing mice and induced widespread apoptosis. Expression analysis and conditional deletion studies showed that Trp53 (p53) was the predominant transcriptional regulator activated by radiation and was strictly required for treatment response. Deletion of Bax, which blocked apoptosis downstream of p53, was sufficient to render tumors radiation resistant. In apoptosis-incompetent, Bax-deleted tumors, radiation activated p53-dependent transcription without provoking cell death and caused two discrete populations to emerge. Most radiated tumor cells underwent terminal differentiation. Perivascular cells, however, quickly resumed proliferation despite p53 activation, behaved as stem cells, and rapidly drove recurrence. These data show that radiation must induce apoptosis in tumor stem cells to be effective. Mutations that disable the intrinsic apoptotic pathways are sufficient to impart radiation resistance. We suggest that medulloblastomas are typically sensitive to DNA-damaging therapies, because they retain apoptosis competence. Cancer Res; 76(11); 3211-23. (c)2016 AACR. PMID- 27197167 TI - MYC Is a Crucial Mediator of TGFbeta-Induced Invasion in Basal Breast Cancer. AB - Basal subtype breast cancers have a particularly poor prognosis, with high invasiveness and resistance to most targeted therapies. TGFbeta and MYC drive central features of basal breast cancer: TGFbeta is an autocrine and paracrine signaling factor that drives cell invasion and metastasis, and MYC is a central regulator of cellular proliferation that is upregulated in many cancer types. We show here that genetic or pharmacologic inhibition of MYC in MCF10A basal breast cells results in increased sensitivity to TGFbeta-stimulated invasion and metastasis and also show that this signaling loop is dependent on activation of SRC. Analysis of human breast cancer datasets and additional experiments with breast cancer cell lines further suggest the relevance of this signaling loop in basal, but not luminal, breast cancers. Our results imply precaution should be taken when utilizing therapeutic inhibitors of MYC with basal breast cancer patients as this could lead to increased metastasis; however, simultaneous pharmacologic inhibition of SRC and MYC for these patients could facilitate the antiproliferative effects of MYC inhibition while blocking the consequent promotion of metastasis. Cancer Res; 76(12); 3520-30. (c)2016 AACR. PMID- 27197168 TI - mda-7/IL-24 Induces Cell Death in Neuroblastoma through a Novel Mechanism Involving AIF and ATM. AB - Advanced stages of neuroblastoma, the most common extracranial malignant solid tumor of the central nervous system in infants and children, are refractive to therapy. Ectopic expression of melanoma differentiation-associated gene 7/interleukin-24 (mda-7/IL-24) promotes broad-spectrum antitumor activity in vitro, in vivo in preclinical animal models, and in a phase I clinical trial in patients with advanced cancers without harming normal cells. mda-7/IL-24 exerts cancer-specific toxicity (apoptosis or toxic autophagy) by promoting endoplasmic reticulum stress and modulating multiple signal transduction pathways regulating cancer cell growth, invasion, metastasis, survival, and angiogenesis. To enhance cancer-selective expression and targeted anticancer activity of mda-7/IL-24, we created a tropism-modified cancer terminator virus (Ad.5/3-CTV), which selectively replicates in cancer cells producing robust expression of mda-7/IL-24 We now show that Ad.5/3-CTV induces profound neuroblastoma antiproliferative activity and apoptosis in a caspase-3/9-independent manner, both in vitro and in vivo in a tumor xenograft model. Ad.5/3-CTV promotes these effects through a unique pathway involving apoptosis-inducing factor (AIF) translocation into the nucleus. Inhibiting AIF rescued neuroblastoma cells from Ad.5/3-CTV-induced cell death, whereas pan-caspase inhibition failed to promote survival. Ad.5/3-CTV infection of neuroblastoma cells increased ATM phosphorylation instigating nuclear translocation and increased gamma-H2AX, triggering nuclear translocation and intensified expression of AIF. These results were validated further using two ATM small-molecule inhibitors that attenuated PARP cleavage by inhibiting gamma H2AX, which in turn inhibited AIF changes in Ad.5/3-CTV-infected neuroblastoma cells. Taken together, we elucidate a novel pathway for mda-7/IL-24-induced caspase-independent apoptosis in neuroblastoma cells mediated through modulation of AIF, ATM, and gamma-H2AX. Cancer Res; 76(12); 3572-82. (c)2016 AACR. PMID- 27197169 TI - The Small Molecule IMR-1 Inhibits the Notch Transcriptional Activation Complex to Suppress Tumorigenesis. AB - In many cancers, aberrant Notch activity has been demonstrated to play a role in the initiation and maintenance of the neoplastic phenotype and in cancer stem cells, which may allude to its additional involvement in metastasis and resistance to therapy. Therefore, Notch is an exceedingly attractive therapeutic target in cancer, but the full range of potential targets within the pathway has been underexplored. To date, there are no small-molecule inhibitors that directly target the intracellular Notch pathway or the assembly of the transcriptional activation complex. Here, we describe an in vitro assay that quantitatively measures the assembly of the Notch transcriptional complex on DNA. Integrating this approach with computer-aided drug design, we explored potential ligand binding sites and screened for compounds that could disrupt the assembly of the Notch transcriptional activation complex. We identified a small-molecule inhibitor, termed Inhibitor of Mastermind Recruitment-1 (IMR-1), that disrupted the recruitment of Mastermind-like 1 to the Notch transcriptional activation complex on chromatin, thereby attenuating Notch target gene transcription. Furthermore, IMR-1 inhibited the growth of Notch-dependent cell lines and significantly abrogated the growth of patient-derived tumor xenografts. Taken together, our findings suggest that a novel class of Notch inhibitors targeting the transcriptional activation complex may represent a new paradigm for Notch based anticancer therapeutics, warranting further preclinical characterization. Cancer Res; 76(12); 3593-603. (c)2016 AACR. PMID- 27197170 TI - Inhibition of PAI-1 Limits Tumor Angiogenesis Regardless of Angiogenic Stimuli in Malignant Pleural Mesothelioma. AB - Malignant pleural mesothelioma (MPM) is an aggressive malignant tumor that secretes various angiogenic factors. The main inhibitor of plasminogen activators, PAI-1 (SERPINE1), has been implicated in tumor progression and angiogenesis, and high PAI-1 expression has been associated with poor prognosis in MPM patients. In this study, we examined the antiangiogenic effects of PAI-1 inhibition in MPM. We administered the PAI-1 inhibitor, SK-216, to orthotopic mouse models in which MPM cells expressing high levels of VEGF (VEGFA) or bFGF (FGF2) were intrapleurally transplanted. SK-216 administration reduced tumor weights and the degree of angiogenesis in intrapleural tumors, irrespective of their angiogenic expression profiles. In addition, a combination of SK-216 and the chemotherapeutic agent cisplatin significantly reduced tumor weights compared with monotherapy, prolonging the survival of animals compared with cisplatin treatment alone. Furthermore, SK-216 inhibited migration and tube formation of cultured human umbilical vein endothelial cells induced by various angiogenic factors known to be secreted by MPM. These findings suggest that PAI-1 inactivation by SK-216 may represent a general strategy for inhibiting angiogenesis, including for the treatment of MPM. Cancer Res; 76(11); 3285-94. (c)2016 AACR. PMID- 27197171 TI - MYC-Driven Neuroblastomas Are Addicted to a Telomerase-Independent Function of Dyskerin. AB - The RNA-binding protein dyskerin, encoded by the DKC1 gene, functions as a core component of the telomerase holoenzyme as well as ribonuclear protein complexes involved in RNA processing and ribosome biogenesis. The diverse roles of dyskerin across many facets of RNA biology implicate its potential contribution to malignancy. In this study, we examined the expression and function of dyskerin in neuroblastoma. We show that DKC1 mRNA levels were elevated relative to normal cells across a panel of 15 neuroblastoma cell lines, where both N-Myc and c-Myc directly targeted the DKC1 promoter. Upregulation of MYCN was shown to dramatically increase DKC1 expression. In two independent neuroblastoma patient cohorts, high DKC1 expression correlated strongly with poor event-free and overall survival (P < 0.0001), independently of established prognostic factors. RNAi-mediated depletion of dyskerin inhibited neuroblastoma cell proliferation, including cells immortalized via the telomerase-independent ALT mechanism. Furthermore, dyskerin attenuation impaired anchorage-independent proliferation and tumor growth. Overexpression of the telomerase RNA component, hTR, demonstrated that this proliferative impairment was not a consequence of telomerase suppression. Instead, ribosomal stress, evidenced by depletion of small nucleolar RNAs and nuclear dispersal of ribosomal proteins, was the likely cause of the proliferative impairment in dyskerin-depleted cells. Accordingly, dyskerin suppression caused p53-dependent G1 cell-cycle arrest in p53 wild-type cells, and a p53-independent pathway impaired proliferation in cells with p53 dysfunction. Together, our findings highlight dyskerin as a new therapeutic target in neuroblastoma with crucial telomerase-independent functions and broader implications for the spectrum of malignancies driven by MYC family oncogenes. Cancer Res; 76(12); 3604-17. (c)2016 AACR. PMID- 27197172 TI - Autophagy Differentially Regulates Distinct Breast Cancer Stem-like Cells in Murine Models via EGFR/Stat3 and Tgfbeta/Smad Signaling. AB - Cancer stem-like cells contribute to tumor heterogeneity and have been implicated in disease relapse and drug resistance. Here we show the coexistence of distinct breast cancer stem-like cells (BCSC) as identified by ALDH(+) and CD29(hi)CD61(+) markers, respectively, in murine models of breast cancer. While both BCSC exhibit enhanced tumor-initiating potential, CD29(hi)CD61(+) BCSC displayed increased invasive abilities and higher expression of epithelial-to-mesenchymal transition and mammary stem cell-associated genes, whereas ALDH(+) BCSC were more closely associated with luminal progenitors. Attenuating the autophagy regulator FIP200 diminished the tumor-initiating properties of both ALDH(+) and CD29(hi)CD61(+) BCSC, as achieved by impairing either the Stat3 or TGFbeta/Smad pathways, respectively. Furthermore, combining the Stat3 inhibitor Stattic and the Tgfbeta R1 inhibitor LY-2157299 inhibited the formation of both epithelial and mesenchymal BCSC colonies. In vivo, this combination treatment was sufficient to limit tumor growth and reduce BCSC number. Overall, our findings reveal a differential dependence of heterogeneous BCSC populations on divergent signaling pathways, with implications on how to tailor drug combinations to improve therapeutic efficacy. Cancer Res; 76(11); 3397-410. (c)2016 AACR. PMID- 27197173 TI - Sustained Accumulation of Microtubule-Binding Chemotherapy Drugs in the Peripheral Nervous System: Correlations with Time Course and Neurotoxic Severity. AB - Chemotherapy-induced peripheral neuropathy is a dose-limiting side effect of many antineoplastic agents, but the mechanisms underlying the toxicities are unclear. At their MTDs, the microtubule-binding drugs paclitaxel and ixabepilone induce more severe neuropathy in mice relative to eribulin mesylate, paralleling their toxicity profiles in clinic. We hypothesized that the severity of their neurotoxic effects might be explained by the levels at which they accumulate in the peripheral nervous system. To test this hypothesis, we compared their pharmacokinetics and distribution in peripheral nerve tissue. After administration of a single intravenous dose, each drug was rapidly cleared from plasma but all persisted in the dorsal root ganglia (DRG) and sciatic nerve (SN) for up to 72 hours. Focusing on paclitaxel and eribulin, we performed a 2-week MTD-dosing regimen, followed by a determination of drug pharmacokinetics, tissue distribution, and multiple functional measures of peripheral nerve toxicity for 4 weeks. Consistent with the acute dosing study, both drugs persisted in peripheral nervous tissues for weeks, in contrast to their rapid clearance from plasma. Notably, although eribulin exhibited greater DRG and SN penetration than paclitaxel, the neurotoxicity observed functionally was consistently more severe with paclitaxel. Overall, our results argue that sustained exposure of microtubule-binding chemotherapeutic agents in peripheral nerve tissues cannot by itself account for their associated neurotoxicity. Cancer Res; 76(11); 3332-9. (c)2016 AACR. PMID- 27197175 TI - Activation of the Lin28/let-7 Axis by Loss of ESE3/EHF Promotes a Tumorigenic and Stem-like Phenotype in Prostate Cancer. AB - Although cancer stem-like cells (CSC) are thought to be the most tumorigenic, metastatic, and therapy-resistant cell subpopulation within human tumors, current therapies target bulk tumor cells while tending to spare CSC. In seeking to understand mechanisms needed to acquire and maintain a CSC phenotype in prostate cancer, we investigated connections between the ETS transcription factor ESE3/EHF, the Lin28/let-7 microRNA axis, and the CSC subpopulation in this malignancy. In normal cells, we found that ESE3/EHF bound and repressed promoters for the Lin28A and Lin28B genes while activating transcription and maturation of the let-7 microRNAs. In cancer cells, reduced expression of ESE3/EHF upregulated Lin28A and Lin28B and downregulated the let-7 microRNAs. Notably, we found that deregulation of the Lin28/let-7 axis with reduced production of let-7 microRNAs was critical for cell transformation and expansion of prostate CSC. Moreover, targeting Lin28A/Lin28B in cell lines and tumor xenografts mimicked the effects of ESE3/EHF and restrained tumor-initiating and self-renewal properties of prostate CSC both in vitro and in vivo These results establish that tight control by ESE3/EHF over the Lin28/let-7 axis is a critical barrier to malignant transformation, and they also suggest new strategies to antagonize CSC in human prostate cancer for therapeutic purposes. Cancer Res; 76(12); 3629-43. (c)2016 AACR. PMID- 27197174 TI - SIRT2-Mediated Deacetylation and Tetramerization of Pyruvate Kinase Directs Glycolysis and Tumor Growth. AB - Sirtuins participate in sensing nutrient availability and directing metabolic activity to match energy needs with energy production and consumption. However, the pivotal targets for sirtuins in cancer are mainly unknown. In this study, we identify the M2 isoform of pyruvate kinase (PKM2) as a critical target of the sirtuin SIRT2 implicated in cancer. PKM2 directs the synthesis of pyruvate and acetyl-CoA, the latter of which is transported to mitochondria for use in the Krebs cycle to generate ATP. Enabled by a shotgun mass spectrometry analysis founded on tissue culture models, we identified a candidate SIRT2 deacetylation target at PKM2 lysine 305 (K305). Biochemical experiments including site-directed mutants that mimicked constitutive acetylation suggested that acetylation reduced PKM2 activity by preventing tetramerization to the active enzymatic form. Notably, ectopic overexpression of a deacetylated PKM2 mutant in Sirt2-deficient mammary tumor cells altered glucose metabolism and inhibited malignant growth. Taken together, our results argued that loss of SIRT2 function in cancer cells reprograms their glycolytic metabolism via PKM2 regulation, partially explaining the tumor-permissive phenotype of mice lacking Sirt2 Cancer Res; 76(13); 3802-12. (c)2016 AACR. PMID- 27197176 TI - Autocrine Secretion of Progastrin Promotes the Survival and Self-Renewal of Colon Cancer Stem-like Cells. AB - Subpopulations of cancer stem-like cells (CSC) are thought to drive tumor progression and posttreatment recurrence in multiple solid tumors. However, the mechanisms that maintain stable proportions of self-renewing CSC within heterogeneous tumors under homeostatic conditions remain poorly understood. Progastrin is a secreted peptide that exhibits tumor-forming potential in colorectal cancer, where it regulates pathways known to modulate colon CSC behaviors. In this study, we investigated the role of progastrin in regulating CSC phenotype in advanced colorectal cancer. Progastrin expression and secretion were highly enriched in colon CSC isolated from human colorectal cancer cell lines and colon tumor biopsies. Progastrin expression promoted CSC self-renewal and survival, whereas its depletion by RNA interference-mediated or antibody mediated strategies altered the homeostatic proportions of CSC cells within heterogeneous colorectal cancer tumors. Progastrin downregulation also decreased the frequency of ALDH(high) cells, impairing their tumor-initiating potential, and inhibited the high glycolytic activity of ALDH(high) CSC to limit their self renewal capability. Taken together, our results show how colorectal CSC maintain their tumor-initiating and self-renewal capabilities by secreting progastrin, thereby contributing to the tumor microenvironment to support malignancy. Cancer Res; 76(12); 3618-28. (c)2016 AACR. PMID- 27197177 TI - Cancer Therapy Directed by Comprehensive Genomic Profiling: A Single Center Study. AB - Innovative molecular diagnostics deployed in the clinic enable new ways to stratify patients into appropriate treatment regimens. These approaches may resolve a major challenge for early-phase clinical trials, which is to recruit patients who, while having failed previous treatments, may nevertheless respond to molecularly targeted drugs. We report the findings of a prospective, single center study conducted in patients with diverse refractory cancers who underwent comprehensive genomic profiling (CGP; next-generation sequencing, 236 genes). Of the 500 patients enrolled, 188 (37.6%) received either matched (N = 122/188, 65%) or unmatched therapy (N = 66/188, 35%). The most common reasons that patients were not evaluable for treatment included insufficient tissue, death, or hospice transfer. The median number of molecular alterations per patient was five (range, 1-14); median number of prior therapies, four. The most common diagnoses were ovarian cancer (18%), breast cancer (16%), sarcoma (13%), and renal cancer (7%). Of the 339 successfully profiled patients, 317 (93.5%) had at least one potentially actionable alteration. By calculating matching scores, based on the number of drug matches and genomic aberrations per patient, we found that high scores were independently associated with a greater frequency of stable disease >=6 months/partial/complete remission [22% (high scores) vs. 9% (low scores), P = 0.024], longer time-to-treatment failure [hazard ratio (HR) = 0.52; 95% confidence interval (CI) = 0.36-0.74; P = 0.0003], and survival (HR = 0.65; 95% CI = 0.43-1.0; P = 0.05). Collectively, this study offers a clinical proof of concept for the utility of CGP in assigning therapy to patients with refractory malignancies, especially in those patients with multiple genomic aberrations for whom combination therapies could be implemented. Cancer Res; 76(13); 3690-701. (c)2016 AACR. PMID- 27197179 TI - T-cell Landscape in a Primary Melanoma Predicts the Survival of Patients with Metastatic Disease after Their Treatment with Dendritic Cell Vaccines. AB - Tumor-infiltrating lymphocytes appear to be a predictor of survival in many cancers, including cutaneous melanoma. We applied automated multispectral imaging to determine whether density and distribution of T cells within primary cutaneous melanoma tissue correlate with survival of metastatic melanoma patients after dendritic cell (DC) vaccination. CD3(+) T cell infiltration in primary tumors from 77 metastatic melanoma patients was quantified using the ratio of intratumoral versus peritumoral T-cell densities (I/P ratio). Patients with longer survival after DC vaccination had stronger T-cell infiltration than patients with shorter survival in a discovery cohort of 19 patients (P = 0.000026) and a validation cohort of 39 patients (P = 0.000016). I/P ratio was the strongest predictor of survival in a multivariate analysis including M substage and serum lactate dehydrogenase level. To evaluate I/P ratio as a predictive biomarker, we analyzed 19 chemotherapy-treated patients. Longer survival times of DC-vaccinated compared with chemotherapy-treated patients was observed for high (P = 0.000566), but not low (P = 0.154) I/P ratios. In conclusion, T-cell infiltration into primary melanoma is a strong predictor of survival after DC vaccination in metastatic melanoma patients who, on average, started this therapy several years after primary tumor resection. The infiltration remains predictive even after adjustment for late-stage prognostic markers. Our findings suggest that the I/P ratio is a potential predictive biomarker for treatment selection. Cancer Res; 76(12); 3496-506. (c)2016 AACR. PMID- 27197178 TI - Burden of Nonsynonymous Mutations among TCGA Cancers and Candidate Immune Checkpoint Inhibitor Responses. AB - Immune checkpoint inhibitor treatment represents a promising approach toward treating cancer and has been shown to be effective in a subset of melanoma, non small cell lung cancer (NSCLC), and kidney cancers. Recent studies have suggested that the number of nonsynonymous mutations (NsM) can be used to select melanoma and NSCLC patients most likely to benefit from checkpoint inhibitor treatment. It is hypothesized that a higher burden of NsM generates novel epitopes and gene products, detected by the immune system as foreign. We conducted an assessment of NsM across 7,757 tumor samples drawn from 26 cancers sequenced in the Cancer Genome Atlas (TCGA) Project to estimate the subset of cancers (both types and fractions thereof) that fit the profile suggested for melanoma and NSCLC. An additional independent set of 613 tumors drawn from 5 cancers were analyzed for replication. An analysis of the receiver operating characteristic curves of published data on checkpoint inhibitor response in melanoma and NSCLC data estimates a cutoff of 192 NsM with 74% sensitivity and 59.3% specificity to discriminate potential clinical benefit. Across the 7,757 samples of TCGA, 16.2% displayed an NsM count that exceeded the threshold of 192. It is notable that more than 30% of bladder, colon, gastric, and endometrial cancers have NsM counts above 192, which was also confirmed in melanoma and NSCLC. Our data could inform the prioritization of tumor types (and subtypes) for possible clinical trials to investigate further indications for effective use of immune checkpoint inhibitors, particularly in adult cancers. Cancer Res; 76(13); 3767-72. (c)2016 AACR. PMID- 27197180 TI - NOTCH Signaling Regulates Asymmetric Cell Fate of Fast- and Slow-Cycling Colon Cancer-Initiating Cells. AB - Colorectal cancer cells with stem-like properties, referred to as colon cancer initiating cells (CCIC), have high tumorigenic potential. While CCIC can differentiate to promote cellular heterogeneity, it remains unclear whether CCIC within a tumor contain distinct subpopulations. Here, we describe the co existence of fast- and slow-cycling CCIC, which can undergo asymmetric division to generate each other, highlighting CCIC plasticity and interconvertibility. Fast-cycling CCIC express markers, such as LGR5 and CD133, rely on MYC for their proliferation, whereas slow-cycling CCIC express markers, such as BMI1 and hTERT, are independent of MYC. NOTCH signaling promotes asymmetric cell fate, regulating the balance between these two populations. Overall, our results illuminate the basis for CCIC heterogeneity and plasticity by defining a direct interconversion mechanism between slow- and fast-cycling CCIC. Cancer Res; 76(11); 3411-21. (c)2016 AACR. PMID- 27197181 TI - Ly6E/K Signaling to TGFbeta Promotes Breast Cancer Progression, Immune Escape, and Drug Resistance. AB - Stem cell antigen Sca-1 is implicated in murine cancer stem cell biology and breast cancer models, but the role of its human homologs Ly6K and Ly6E in breast cancer are not established. Here we report increased expression of Ly6K/E in human breast cancer specimens correlates with poor overall survival, with an additional specific role for Ly6E in poor therapeutic outcomes. Increased expression of Ly6K/E also correlated with increased expression of the immune checkpoint molecules PDL1 and CTLA4, increased tumor-infiltrating T regulatory cells, and decreased natural killer (NK) cell activation. Mechanistically, Ly6K/E was required for TGFbeta signaling and proliferation in breast cancer cells, where they contributed to phosphorylation of Smad1/5 and Smad2/3. Furthermore, Ly6K/E promoted cytokine-induced PDL1 expression and activation and binding of NK cells to cancer cells. Finally, we found that Ly6K/E promoted drug resistance and facilitated immune escape in this setting. Overall, our results establish a pivotal role for a Ly6K/E signaling axis involving TGFbeta in breast cancer pathophysiology and drug response, and highlight this signaling axis as a compelling realm for therapeutic invention. Cancer Res; 76(11); 3376-86. (c)2016 AACR. PMID- 27197183 TI - miR-17-92/p38alpha Dysregulation Enhances Wnt Signaling and Selects Lgr6+ Cancer Stem-like Cells during Lung Adenocarcinoma Progression. AB - Defining the molecular and cellular roots of lung cancer relapse after initial treatment remains an imperative to improve survival. Here we report that the lung stem cell marker Lgr6 becomes enriched in non-small cell lung cancer (NSCLC) cells during malignant progression. Lgr6(+) NSCLC cells displayed self-renewal and differentiation properties along with a higher tumorigenic potential. Mechanistic investigations suggested that a defective repression of the miR-17-92 gene cluster was responsible for evolution of a selection for outgrowth of Lgr6(+) NSCLC cells. High levels of expression of miR-19 family members were found to target and downregulate levels of p38alpha kinase, providing a specific survival signal for Lgr6(+) cells as mediated by increased Wnt/beta-catenin activity. Our results identify a specific stem-like cell population in NSCLC with increased malignant potential, the elucidation of which may enable earlier prognosis and possibly the development of more effective targeted treatments. Cancer Res; 76(13); 4012-22. (c)2016 AACR. PMID- 27197182 TI - ICOS Promotes the Function of CD4+ Effector T Cells during Anti-OX40-Mediated Tumor Rejection. AB - ICOS is a T-cell coregulatory receptor that provides a costimulatory signal to T cells during antigen-mediated activation. Antitumor immunity can be improved by ICOS-targeting therapies, but their mechanism of action remains unclear. Here, we define the role of ICOS signaling in antitumor immunity using a blocking, nondepleting antibody against ICOS ligand (ICOS-L). ICOS signaling provided critical support for the effector function of CD4(+) Foxp3(-) T cells during anti OX40-driven tumor immune responses. By itself, ICOS-L blockade reduced accumulation of intratumoral T regulatory cells (Treg), but it was insufficient to substantially inhibit tumor growth. Furthermore, it did not impede antitumor responses mediated by anti-4-1BB-driven CD8(+) T cells. We found that anti-OX40 efficacy, which is based on Treg depletion and to a large degree on CD4(+) effector T cell (Teff) responses, was impaired with ICOS-L blockade. In contrast, the provision of additional ICOS signaling through direct ICOS-L expression by tumor cells enhanced tumor rejection and survival when administered along with anti-OX40 therapy. Taken together, our results showed that ICOS signaling during antitumor responses acts on both Teff and Treg cells, which have opposing roles in promoting immune activation. Thus, effective therapies targeting the ICOS pathway should seek to promote ICOS signaling specifically in effector CD4(+) T cells by combining ICOS agonism and Treg depletion. Cancer Res; 76(13); 3684-9. (c)2016 AACR. PMID- 27197184 TI - M-COPA, a Golgi Disruptor, Inhibits Cell Surface Expression of MET Protein and Exhibits Antitumor Activity against MET-Addicted Gastric Cancers. AB - The Golgi apparatus is responsible for transporting, processing, and sorting numerous proteins in the cell, including cell surface-expressed receptor tyrosine kinases (RTK). The small-molecule compound M-COPA [2-methylcoprophilinamide (AMF 26)] disrupts the Golgi apparatus by inhibiting the activation of Arf1, resulting in suppression of tumor growth. Here, we report an evaluation of M-COPA activity against RTK-addicted cancers, focusing specifically on human gastric cancer (GC) cells with or without MET amplification. As expected, the MET-addicted cell line MKN45 exhibited a better response to M-COPA than cell lines without MET amplification. Upon M-COPA treatment, cell surface expression of MET was downregulated with a concurrent accumulation of its precursor form. M-COPA also reduced levels of the phosphorylated form of MET along with the downstream signaling molecules Akt and S6. Similar results were obtained in additional GC cell lines with amplification of MET or the FGF receptor FGFR2 MKN45 murine xenograft experiments demonstrated the antitumor activity of M-COPA in vivo Taken together, our results offer an initial preclinical proof of concept for the use of M-COPA as a candidate treatment option for MET-addicted GC, with broader implications for targeting the Golgi apparatus as a novel cancer therapeutic approach. Cancer Res; 76(13); 3895-903. (c)2016 AACR. PMID- 27197185 TI - miR-339-3p Is a Tumor Suppressor in Melanoma. AB - Determinants of invasion and metastasis in cancer remain of great interest to define. Here, we report the definition of miR-339-3p as a novel tumor suppressive microRNA that blocks melanoma cell invasion without affecting cell survival. miR 339-3p was identified by a comprehensive functional screen of a human miRNA mimetic library in a cell-based assay for invasion by the melanoma cell line A375. miR-339-3p was determined as a strong inhibitor of invasion differentially expressed in melanoma cells and healthy melanocytes. MCL1 was defined as a target for downregulation by miR-339-3p, functioning through direct interaction with the 3' untranslated region of MCL1 mRNA. Blocking miR-339-3p by an antagomiR was sufficient to increase melanoma cell invasion, an effect that could be phenocopied by RNAi-mediated silencing of MCL1. In vivo studies established that miR-339-3p overexpression was sufficient to decrease lung colonization by A375 melanoma cells in NSG mice, relative to control cells. Overall, our results defined miR-339-3p as a melanoma tumor suppressor, the levels of which contributes to invasive aggressiveness. Cancer Res; 76(12); 3562-71. (c)2016 AACR. PMID- 27197186 TI - Antibody-Targeted Chemotherapy for the Treatment of Melanoma. AB - Antibody-directed chemotherapy (ADC) offers an advantage over conventional chemotherapy because it provides antibody-directed targeting, with resultant improvement in therapeutic efficacy and reduced toxicity. Despite extensive research, with notable exceptions, broad clinical application of ADC remains elusive; major hurdles include the instability of antibody-chemotherapy linkers and reduced tumor toxicity of the chemotherapy when bound to the antibody. To address these challenges, we have developed a platform technology that utilizes the nab-paclitaxel formulation of paclitaxel, Abraxane, in which hydrophobic paclitaxel is suspended in 130-nm albumin nanoparticles and thus made water soluble. We have developed a method to noncovalently coat the Abraxane nanoparticle with recombinant mAbs (anti-VEGF, bevacizumab) and guide Abraxane delivery into tumors in a preclinical model of human A375 melanoma. Here, we define the binding characteristics of bevacizumab and Abraxane, demonstrate that the chemotherapy agent retains its cytotoxic effect, while the antibody maintains the ability to bind its ligand when the two are present in a single nanoparticle (AB160), and show that the nanoparticle yields improved antitumor efficacy in a preclinical human melanoma xenograft model. Further data suggest that numerous therapeutic monoclonal IgG1 antibodies may be utilized in this platform, which has implications for many solid and hematologic malignancies. Cancer Res; 76(13); 3954-64. (c)2016 AACR. PMID- 27197187 TI - IL6 Blockade Reprograms the Lung Tumor Microenvironment to Limit the Development and Progression of K-ras-Mutant Lung Cancer. AB - Activating mutations of K-ras are the most common oncogenic alterations found in lung cancer. Unfortunately, attempts to target K-ras-mutant lung tumors have thus far failed, clearly indicating the need for new approaches in patients with this molecular profile. We have previously shown NF-kappaB activation, release of IL6, and activation of its responsive transcription factor STAT3 in K-ras-mutant lung tumors, which was further amplified by the tumor-enhancing effect of chronic obstructive pulmonary disease (COPD)-type airway inflammation. These findings suggest an essential role for this inflammatory pathway in K-ras-mutant lung tumorigenesis and its enhancement by COPD. Therefore, here we blocked IL6 using a monoclonal anti-IL6 antibody in a K-ras-mutant mouse model of lung cancer in the absence or presence of COPD-type airway inflammation. IL6 blockade significantly inhibited lung cancer promotion, tumor cell-intrinsic STAT3 activation, tumor cell proliferation, and angiogenesis markers. Moreover, IL6 inhibition reduced expression of protumor type 2 molecules (arginase 1, Fizz 1, Mgl, and IDO), number of M2-type macrophages and granulocytic myeloid-derived suppressor cells, and protumor T-regulatory/Th17 cell responses. This was accompanied by increased expression of antitumor type 1 molecule (Nos2), and antitumor Th1/CD8 T-cell responses. Our study demonstrates that IL6 blockade not only has direct intrinsic inhibitory effect on tumor cells, but also reeducates the lung microenvironment toward an antitumor phenotype by altering the relative proportion between protumor and antitumor immune cells. This information introduces IL6 as a potential druggable target for prevention and treatment of K-ras-mutant lung tumors. Cancer Res; 76(11); 3189-99. (c)2016 AACR. PMID- 27197189 TI - Ribosomal Protein Rpl22 Controls the Dissemination of T-cell Lymphoma. AB - Mutations in ribosomal proteins cause bone marrow failure syndromes associated with increased cancer risk, but the basis by which they do so remains unclear. We reported previously that the ribosomal protein Rpl22 is a tumor suppressor in T cell acute lymphoblastic leukemia/lymphoma (T-ALL), and that loss of just one Rpl22 allele accelerates T-cell lymphomagenesis by activating NF-kappaB and inducing the stem cell factor Lin28B. Here, we show that, paradoxically, loss of both alleles of Rpl22 restricts lymphoma progression through a distinct effect on migration of malignant cells out of the thymus. Lymphoma-prone AKT2-transgenic or PTEN-deficient mice on an Rpl22(-/-) background developed significantly larger and markedly more vascularized thymic tumors than those observed in Rpl22(+/+) control mice. But, unlike Rpl22(+/+) or Rpl22(+/-) tumors, Rpl22(-/-) lymphomas did not disseminate to the periphery and were retained in the thymus. We traced the defect in the Rpl22(-/-) lymphoma migratory capacity to downregulation of the KLF2 transcription factor and its targets, including the key migratory factor sphingosine 1-phosphate receptor 1 (S1PR1). Indeed, reexpression of S1PR1 in Rpl22-deficient tumor cells restores their migratory capacity in vitro The regulation of KLF2 and S1PR1 by Rpl22 appears to be proximal as Rpl22 reexpression in Rpl22-deficient lymphoma cells restores expression of KLF2 and S1P1R, while Rpl22 knockdown in Rpl22-sufficient lymphomas attenuates their expression. Collectively, these data reveal that, while loss of one copy of Rpl22 promotes lymphomagenesis and disseminated disease, loss of both copies impairs responsiveness to migratory cues and restricts malignant cells to the thymus. Cancer Res; 76(11); 3387-96. (c)2016 AACR. PMID- 27197188 TI - Renalase Expression by Melanoma and Tumor-Associated Macrophages Promotes Tumor Growth through a STAT3-Mediated Mechanism. AB - To sustain their proliferation, cancer cells overcome negative-acting signals that restrain their growth and promote senescence and cell death. Renalase (RNLS) is a secreted flavoprotein that functions as a survival factor after ischemic and toxic injury, signaling through the plasma calcium channel PMCA4b to activate the PI3K/AKT and MAPK pathways. We show that RNLS expression is increased markedly in primary melanomas and CD163(+) tumor-associated macrophages (TAM). In clinical specimens, RNLS expression in the tumor correlated inversely with disease specific survival, suggesting a pathogenic role for RNLS. Attenuation of RNLS by RNAi, blocking antibodies, or an RNLS-derived inhibitory peptide decreased melanoma cell survival, and anti-RNLS therapy blocked tumor growth in vivo in murine xenograft assays. Mechanistic investigations showed that increased apoptosis in tumor cells was temporally related to p38 MAPK-mediated Bax activation and that increased cell growth arrest was associated with elevated expression of the cell-cycle inhibitor p21. Overall, our results established a role for the secreted flavoprotein RNLS in promoting melanoma cell growth and CD163(+) TAM in the tumor microenvironment, with potential therapeutic implications for the management of melanoma. Cancer Res; 76(13); 3884-94. (c)2016 AACR. PMID- 27197190 TI - A Novel MIF Signaling Pathway Drives the Malignant Character of Pancreatic Cancer by Targeting NR3C2. AB - Pancreatic cancers with aberrant expression of macrophage migration inhibitory factor (MIF) are particularly aggressive. To identify key signaling pathways that drive disease aggressiveness in tumors with high MIF expression, we analyzed the expression of coding and noncoding genes in high and low MIF-expressing tumors in multiple cohorts of pancreatic ductal adenocarcinoma (PDAC) patients. The key genes and pathways identified were linked to patient survival and were mechanistically, functionally, and clinically characterized using cell lines, a genetically engineered mouse model, and PDAC patient cohorts. Here, we report evidence of a novel MIF-driven signaling pathway that inhibits the orphan nuclear receptor NR3C2, a previously undescribed tumor suppressor that impacts aggressiveness and survival in PDAC. Mechanistically, MIF upregulated miR-301b that targeted NR3C2 and suppressed its expression. PDAC tumors expressing high levels of MIF displayed elevated levels of miR-301b and reduced levels of NR3C2. In addition, reduced levels of NR3C2 expression correlated with poorer survival in multiple independent cohorts of PDAC patients. Functional analysis showed that NR3C2 inhibited epithelial-to-mesenchymal transition and enhanced sensitivity to the gemcitabine, a chemotherapeutic drug used in PDAC standard of care. Furthermore, genetic deletion of MIF disrupted a MIF-mir-301b-NR3C2 signaling axis, reducing metastasis and prolonging survival in a genetically engineered mouse model of PDAC. Taken together, our results offer a preclinical proof of principle for candidate therapies to target a newly described MIF-miR-301b-NR3C2 signaling axis for PDAC management. Cancer Res; 76(13); 3838-50. (c)2016 AACR. PMID- 27197193 TI - Systematic Analysis of AU-Rich Element Expression in Cancer Reveals Common Functional Clusters Regulated by Key RNA-Binding Proteins. AB - Defects in AU-rich elements (ARE)-mediated posttranscriptional control can lead to several abnormal processes that underlie carcinogenesis. Here, we performed a systematic analysis of ARE-mRNA expression across multiple cancer types. First, the ARE database (ARED) was intersected with The Cancer Genome Atlas databases and others. A large set of ARE-mRNAs was over-represented in cancer and, unlike non-ARE-mRNAs, correlated with the reversed balance in the expression of the RNA binding proteins tristetraprolin (TTP, ZFP36) and HuR (ELAVL1). Serial statistical and functional enrichment clustering identified a cluster of 11 overexpressed ARE-mRNAs (CDC6, KIF11, PRC1, NEK2, NCAPG, CENPA, NUF2, KIF18A, CENPE, PBK, TOP2A) that negatively correlated with TTP/HuR mRNA ratios and was involved in the mitotic cell cycle. This cluster was upregulated in a number of solid cancers. Experimentally, we demonstrated that the ARE-mRNA cluster is upregulated in a number of tumor breast cell lines when compared with noninvasive and normal-like breast cancer cells. RNA-IP demonstrated the association of the ARE-mRNAs with TTP and HuR. Experimental modulation of TTP or HuR expression led to changes in the mitosis ARE-mRNAs. Posttranscriptional reporter assays confirmed the functionality of AREs. Moreover, TTP augmented mitotic cell-cycle arrest as demonstrated by flow cytometry and histone H3 phosphorylation. We found that poor breast cancer patient survival was significantly associated with low TTP/HuR mRNA ratios and correlated with high levels of the mitotic ARE-mRNA signature. These results significantly broaden the role of AREs and their binding proteins in cancer, and demonstrate that TTP induces an antimitotic pathway that is diminished in cancer. Cancer Res; 76(14); 4068-80. (c)2016 AACR. PMID- 27197192 TI - Improved Survival of HER2+ Breast Cancer Patients Treated with Trastuzumab and Chemotherapy Is Associated with Host Antibody Immunity against the HER2 Intracellular Domain. AB - The addition of trastuzumab to chemotherapy extends survival among patients with HER2(+) breast cancer. Prior work showed that trastuzumab and chemotherapy augments HER2 extracellular domain (ECD)-specific antibodies. The current study investigated whether combination therapy induced immune responses beyond HER2-ECD and, importantly, whether those immune responses were associated with survival. Pretreatment and posttreatment sera were obtained from 48 women with metastatic HER2(+) breast cancer on NCCTG (now Alliance for Clinical Trials in Oncology) studies, N0337 and N983252. IgG to HER2 intracellular domain (ICD), HER2-ECD, p53, IGFBP2, CEA, and tetanus toxoid were examined. Sera from 25 age-matched controls and 26 surgically resected HER2(+) patients were also examined. Prior to therapy, some patients with metastatic disease had elevated antibodies to IGFBP2, p53, HER2-ICD, HER2-ECD, and CEA, but not to tetanus toxin, relative to controls and surgically resected patients. Treatment augmented antibody responses to HER2 ICD in 69% of metastatic patients, which was highly associated with improved progression-free survival (PFS; HR = 0.5, P = 0.0042) and overall survival (OS; HR = 0.7, P = 0.038). Augmented antibody responses to HER2-ICD also correlated (P = 0.03) with increased antibody responses to CEA, IGFBP2, and p53, indicating that treatment induces epitope spreading. Paradoxically, patients who already had high preexisting immunity to HER2-ICD did not respond to therapy with increased antibodies to HER2-ICD and demonstrated poorer PFS (HR = 1.6, P < 0.0001) and OS (HR = 1.4, P = 0.0006). Overall, the findings further demonstrate the importance of the adaptive immune system in the efficacy of trastuzumab-containing regimens. Cancer Res; 76(13); 3702-10. (c)2016 AACR. PMID- 27197194 TI - Rapalogs Efficacy Relies on the Modulation of Antitumor T-cell Immunity. AB - The rapalogs everolimus and temsirolimus that inhibit mTOR signaling are used as antiproliferative drugs in several cancers. Here we investigated the influence of rapalogs-mediated immune modulation on their antitumor efficacy. Studies in metastatic renal cell carcinoma patients showed that everolimus promoted high expansion of FoxP3 (+)Helios(+)Ki67(+) regulatory CD4 T cells (Tregs). In these patients, rapalogs strongly enhanced the suppressive functions of Tregs, mainly in a contact-dependent manner. Paradoxically, a concurrent activation of spontaneous tumor-specific Th1 immunity also occurred. Furthermore, a high rate of Eomes(+)CD8(+) T cells was detected in patients after a long-term mTOR inhibition. We found that early changes in the Tregs/antitumor Th1 balance can differentially shape the treatment efficacy. Patients presenting a shift toward decreased Tregs levels and high expansion of antitumor Th1 cells showed better clinical responses. Studies conducted in tumor-bearing mice confirmed the deleterious effect of rapalogs-induced Tregs via a mechanism involving the inhibition of antitumor T-cell immunity. Consequently, the combination of temsirolimus plus CCR4 antagonist, a receptor highly expressed on rapalogs exposed Tregs, was more effective than monotherapy. Altogether, our results describe for the first time a dual impact of host adaptive antitumor T-cell immunity on the clinical effectiveness of rapalogs and prompt their association with immunotherapies. Cancer Res; 76(14); 4100-12. (c)2016 AACR. PMID- 27197195 TI - mTORC1-Driven Tumor Cells Are Highly Sensitive to Therapeutic Targeting by Antagonists of Oxidative Stress. AB - mTORC1 is a central signaling node in controlling cell growth, proliferation, and metabolism that is aberrantly activated in cancers and certain cancer-associated genetic disorders, such as tuberous sclerosis complex (TSC) and sporadic lymphangioleiomyomatosis. However, while mTORC1-inhibitory compounds (rapamycin and rapalogs) attracted interest as candidate therapeutics, clinical trials have not replicated the promising findings in preclinical models, perhaps because these compounds tend to limit cell proliferation without inducing cell death. In seeking to address this issue, we performed a high-throughput screen for small molecules that could heighten the cytotoxicity of mTORC1 inhibitors. Here we report the discovery that combining inhibitors of mTORC1 and glutamate cysteine ligase (GCLC) can selectively and efficiently trigger apoptosis in Tsc2-deficient cells but not wild-type cells. Mechanistic investigations revealed that coinhibition of mTORC1 and GCLC decreased the level of the intracellular thiol antioxidant glutathione (GSH), thereby increasing levels of reactive oxygen species, which we determined to mediate cell death in Tsc2-deficient cells. Our findings offer preclinical proof of concept for a strategy to selectively increase the cytotoxicity of mTORC1 inhibitors as a therapy to eradicate tumor cells marked by high mTORC1 signaling, based on cotargeting a GSH-controlled oxidative stress pathway. Cancer Res; 76(16); 4816-27. (c)2016 AACR. PMID- 27197191 TI - Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations. AB - Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-stage approach to conduct genome-wide association studies for lung, ovary, breast, prostate, and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820 controls) to identify pleiotropic loci. Findings were replicated in independent association studies (55,789 cases, 330,490 controls). We identified a novel pleiotropic association at 1q22 involving breast and lung squamous cell carcinoma, with eQTL analysis showing an association with ADAM15/THBS3 gene expression in lung. We also identified a known breast cancer locus CASP8/ALS2CR12 associated with prostate cancer, a known cancer locus at CDKN2B-AS1 with different variants associated with lung adenocarcinoma and prostate cancer, and confirmed the associations of a breast BRCA2 locus with lung and serous ovarian cancer. This is the largest study to date examining pleiotropy across multiple cancer-associated loci, identifying common mechanisms of cancer development and progression. Cancer Res; 76(17); 5103 14. (c)2016 AACR. PMID- 27197197 TI - MFG-E8 Drives Melanoma Growth by Stimulating Mesenchymal Stromal Cell-Induced Angiogenesis and M2 Polarization of Tumor-Associated Macrophages. AB - Secretion of the powerful angiogenic factor MFG-E8 by pericytes can bypass the therapeutic effects of anti-VEGF therapy, but the mechanisms by which MFG-E8 acts are not fully understood. In this study, we investigated how this factor acts to promote the growth of melanomas that express it. We found that mouse bone marrow derived mesenchymal stromal cells (MSC) expressed a substantial amount of MFG-E8. To assess its expression from this cell type, we implanted melanoma cells and MSC derived from wild type (WT) or MFG-E8 deficient [knockout (KO)] into mice and monitored tumor growth. Tumor growth and M2 macrophages were each attenuated in subjects coimplanted with KO-MSC compared with WT-MSC. In both xenograft tumors and clinical specimens of melanoma, we found that MFG-E8 expression was heightened near blood vessels where MSC could be found. Through in vitro assays, we confirmed that WT-MSC-conditioned medium was more potent at inducing M2 macrophage polarization, compared with KO-MSC-conditioned medium. VEGF and ET-1 expression in KO-MSC was significantly lower than in WT-MSC, correlating in vivo with reduced tumor growth and numbers of pericytes and M2 macrophages within tumors. Overall, our results suggested that MFG-E8 acts at two levels, by increasing VEGF and ET-1 expression in MSC and by enhancing M2 polarization of macrophages, to increase tumor angiogenesis. Cancer Res; 76(14); 4283-92. (c)2016 AACR. PMID- 27197198 TI - Label-Free Neurosurgical Pathology with Stimulated Raman Imaging. AB - The goal of brain tumor surgery is to maximize tumor removal without injuring critical brain structures. Achieving this goal is challenging as it can be difficult to distinguish tumor from nontumor tissue. While standard histopathology provides information that could assist tumor delineation, it cannot be performed iteratively during surgery as freezing, sectioning, and staining of the tissue require too much time. Stimulated Raman scattering (SRS) microscopy is a powerful label-free chemical imaging technology that enables rapid mapping of lipids and proteins within a fresh specimen. This information can be rendered into pathology-like images. Although this approach has been used to assess the density of glioma cells in murine orthotopic xenografts models and human brain tumors, tissue heterogeneity in clinical brain tumors has not yet been fully evaluated with SRS imaging. Here we profile 41 specimens resected from 12 patients with a range of brain tumors. By evaluating large-scale stimulated Raman imaging data and correlating this data with current clinical gold standard of histopathology for 4,422 fields of view, we capture many essential diagnostic hallmarks for glioma classification. Notably, in fresh tumor samples, we observe additional features, not seen by conventional methods, including extensive lipid droplets within glioma cells, collagen deposition in gliosarcoma, and irregularity and disruption of myelinated fibers in areas infiltrated by oligodendroglioma cells. The data are freely available in a public resource to foster diagnostic training and to permit additional interrogation. Our work establishes the methodology and provides a significant collection of reference images for label-free neurosurgical pathology. Cancer Res; 76(12); 3451-62. (c)2016 AACR. PMID- 27197196 TI - Constitutive Activation of PI3K in Oocyte Induces Ovarian Granulosa Cell Tumors. AB - Cell-cell interactions play crucial roles in the maintenance of tissue homeostasis, a loss of which often leads to varying diseases, including cancer. Here, we report that uncontrolled PI3K activity within oocytes irreversibly transforms granulosa cells (GC), causing GC tumors (GCT) through perturbed local cell communication. Previously, we reported reproductive phenotypes of transgenic mice, in which expression of constitutively active mutant PI3K was induced in primordial oocytes by Gdf9-iCre. The transgenic mice (Cre(+)) demonstrated severe ovarian phenotypes, including the overgrowth of excess ovarian follicles and anovulation. Surprisingly, the Cre(+) mice became cachectic by postnatal day 80 due to bilateral GCT. Although GCT cells proliferated independently of oocytes, local interactions with mutant PI3K-positive oocytes during early folliculogenesis were essential for the GC transformation. Growing GCT cells expressed high levels of inhibin betaA and nuclear SMAD3, and the proliferation rate was positively correlated with a high activin A to inhibin A ratio. These results suggested that the tumor cells stimulated their growth through an activin A autocrine signaling pathway, a hypothesis confirmed by activin A secretion in cultured GCT cells, which proliferated in response. Although communication between the oocyte and surrounding somatic cells is critical for the normal development of ovarian follicles, perturbations in oocyte-GC communication during early folliculogenesis can induce GCT by activating an autocrine growth circuit program in GC. Cancer Res; 76(13); 3851-61. (c)2016 AACR. PMID- 27197199 TI - Adoptive Transfer of CD8+ T Cells Generated from Induced Pluripotent Stem Cells Triggers Regressions of Large Tumors Along with Immunological Memory. AB - Current approaches to adoptive T-cell therapy are limited by the difficulty of obtaining sufficient numbers of T cells against targeted antigens with useful in vivo characteristics. Theoretically, this limitation could be overcome by using induced pluripotent stem cells (iPSC) that could provide an unlimited source of autologous T cells. However, the therapeutic efficacy of iPSC-derived regenerated T cells remains to be demonstrated. Here, we report the first successful reprogramming of T-cell receptor (TCR) transgenic CD8(+) T cells into pluripotency. As part of the work, we established a syngeneic mouse model for evaluating in vitro and in vivo antitumor reactivity of regenerated T cells from iPSCs bearing a rearranged TCR of known antigen specificity. Stably TCR retained T-cell-derived iPSCs differentiated into CD4(+)CD8(+) T cells that expressed CD3 and the desired TCR in vitro Stimulation of iPSC-derived CD4(+)CD8(+) T cells with the cognate antigen in the presence of IL7 and IL15 followed by expansion with IL2, IL7, and IL15 generated large numbers of less-differentiated CD8(+) T cells with antigen-specific potent cytokine production and cytolytic capacity. Furthermore, adoptively transferred iPSC-derived CD8(+) T cells escaped immune rejection, mediated effective regression of large tumors, improved survival, and established antigen-specific immunological memory. Our findings illustrate the translational potential of iPSCs to provide an unlimited number of phenotypically defined, functional, and expandable autologous antigen-specific T cells with the characteristics needed to enable in vivo effectiveness. Cancer Res; 76(12); 3473 83. (c)2016 AACR. PMID- 27197200 TI - Increased Expression of miR-23a Mediates a Loss of Expression in the RAF Kinase Inhibitor Protein RKIP. AB - RAF kinase inhibitor protein (RKIP) is a seminal regulator of intracellular signaling and exhibits both antimetastatic and antitumorigenic properties. Decreased expression of RKIP has been described in several human malignancies, including acute myelogenous leukemia (AML). As the mechanisms leading to RKIP loss in AML are still unclear, we aimed to analyze the potential involvement of miRNAs within this study. miRNA microarray and qPCR data of more than 400 AML patient specimens revealed correlation between decreased expression of RKIP and increased expression of miR-23a, a member of the miR-23a/27a/24-2 cluster. In functional experiments, overexpression of miR-23a decreased RKIP mRNA and protein expression, whereas miR-23a inhibition caused the opposite effect. By using an RKIP 3'-untranslated region luciferase reporter construct with and without mutation or deletion of the putative miR-23a-binding site, we could show that RKIP modulation by miR-23a is mediated via direct binding to this region. Importantly, miR-23a overexpression induced a significant increase of proliferation in hematopoietic cells. Simultaneous transfection of an RKIP expression construct lacking the miR-23a-binding sites reversed this phenotype, indicating that this effect is truly mediated via downregulation of RKIP. Finally, by analyzing more than 4,300 primary patient specimens via database retrieval from The Cancer Genome Atlas, we could highlight the importance of the miR-23a/RKIP axis in a broad range of human cancer entities. In conclusion, we have identified miR-23a as a negative regulator of RKIP expression in AML and have provided data that suggest the importance of our observation beyond this tumor entity. Cancer Res; 76(12); 3644-54. (c)2016 AACR. PMID- 27197202 TI - c-Myb Enhances Breast Cancer Invasion and Metastasis through the Wnt/beta Catenin/Axin2 Pathway. AB - The molecular underpinnings of aggressive breast cancers remain mainly obscure. Here we demonstrate that activation of the transcription factor c-Myb is required for the prometastatic character of basal breast cancers. An analysis of breast cancer patients led us to identify c-Myb as an activator of Wnt/beta-catenin signaling. c-Myb interacted with the intracellular Wnt effector beta-catenin and coactivated the Wnt/beta-catenin target genes Cyclin D1 and Axin2 Moreover, c-Myb controlled metastasis in an Axin2-dependent manner. Expression microarray analyses revealed a positive association between Axin2 and c-Myb, a target of the proinflammatory cytokine IL1beta that was found to be required for IL1beta induced breast cancer cell invasion. Overall, our results identified c-Myb as a promoter of breast cancer invasion and metastasis through its ability to activate Wnt/beta-catenin/Axin2 signaling. Cancer Res; 76(11); 3364-75. (c)2016 AACR. PMID- 27197201 TI - p27 Is a Candidate Prognostic Biomarker and Metastatic Promoter in Osteosarcoma. AB - Metastatic progression is the major cause of death in osteosarcoma, the most common bone malignancy in children and young adults. However, prognostic biomarkers and efficacious targeted treatments for metastatic disease remain lacking. Using an immunoproteomic approach, we discovered that autoantibodies against the cell-cycle kinase inhibitor p27 (KIP1, CDKN1B) were elevated in plasma of high-risk osteosarcoma patients. Using a large cohort of serum samples from osteosarcoma patients (n = 233), we validated that a higher level of the p27 autoantibody significantly correlated with poor overall and event-free survival (P < 0.05). Immunohistochemical analysis also showed that p27 was mislocalized to the cytoplasm in the majority of osteosarcoma cases and in highly metastatic osteosarcoma cell lines. We demonstrated that ectopic expression of cytoplasmic p27 promoted migration and invasion of osteosarcoma cells, whereas shRNA-mediated gene silencing suppressed these effects. In addition, mutations at the p27 phosphorylation sites S10 or T198, but not T157, abolished the migratory and invasive phenotypes. Furthermore, the development of pulmonary metastases increased in mice injected with cells expressing cytoplasmic p27 compared with an empty vector control. Collectively, our findings support further investigation of p27 as a potential prognostic biomarker and therapeutic target in osteosarcoma cases exhibiting aberrant p27 subcellular localization. Cancer Res; 76(13); 4002 11. (c)2016 AACR. PMID- 27197204 TI - Mediator, TATA-binding protein, and RNA polymerase II contribute to low histone occupancy at active gene promoters in yeast. PMID- 27197203 TI - Combined Inhibition of DNMT and HDAC Blocks the Tumorigenicity of Cancer Stem like Cells and Attenuates Mammary Tumor Growth. AB - Recently, impressive technical advancements have been made in the isolation and validation of mammary stem cells and cancer stem cells (CSC), but the signaling pathways that regulate stem cell self-renewal are largely unknown. Furthermore, CSCs are believed to contribute to chemo- and radioresistance. In this study, we used the MMTV-Neu-Tg mouse mammary tumor model to identify potential new strategies for eliminating CSCs. We found that both luminal progenitor and basal stem cells are susceptible to genetic and epigenetic modifications, which facilitate oncogenic transformation and tumorigenic potential. A combination of the DNMT inhibitor 5-azacytidine and the HDAC inhibitor butyrate markedly reduced CSC abundance and increased the overall survival in this mouse model. RNA-seq analysis of CSCs treated with 5-azacytidine plus butyrate provided evidence that inhibition of chromatin modifiers blocks growth-promoting signaling molecules such as RAD51AP1 and SPC25, which play key roles in DNA damage repair and kinetochore assembly. Moreover, RAD51AP1 and SPC25 were significantly overexpressed in human breast tumor tissues and were associated with reduced overall patient survival. In conclusion, our studies suggest that breast CSCs are intrinsically sensitive to genetic and epigenetic modifications and can therefore be significantly affected by epigenetic-based therapies, warranting further investigation of combined DNMT and HDAC inhibition in refractory or drug resistant breast cancer. Cancer Res; 76(11); 3224-35. (c)2016 AACR. PMID- 27197205 TI - Multiplex enhancer-reporter assays uncover unsophisticated TP53 enhancer logic. AB - Transcription factors regulate their target genes by binding to regulatory regions in the genome. Although the binding preferences of TP53 are known, it remains unclear what distinguishes functional enhancers from nonfunctional binding. In addition, the genome is scattered with recognition sequences that remain unoccupied. Using two complementary techniques of multiplex enhancer reporter assays, we discovered that functional enhancers could be discriminated from nonfunctional binding events by the occurrence of a single TP53 canonical motif. By combining machine learning with a meta-analysis of TP53 ChIP-seq data sets, we identified a core set of more than 1000 responsive enhancers in the human genome. This TP53 cistrome is invariably used between cell types and experimental conditions, whereas differences among experiments can be attributed to indirect nonfunctional binding events. Our data suggest that TP53 enhancers represent a class of unsophisticated cell-autonomous enhancers containing a single TP53 binding site, distinct from complex developmental enhancers that integrate signals from multiple transcription factors. PMID- 27197206 TI - Selection and explosive growth alter genetic architecture and hamper the detection of causal rare variants. AB - The role of rare alleles in complex phenotypes has been hotly debated, but most rare variant association tests (RVATs) do not account for the evolutionary forces that affect genetic architecture. Here, we use simulation and numerical algorithms to show that explosive population growth, as experienced by human populations, can dramatically increase the impact of very rare alleles on trait variance. We then assess the ability of RVATs to detect causal loci using simulations and human RNA-seq data. Surprisingly, we find that statistical performance is worst for phenotypes in which genetic variance is due mainly to rare alleles, and explosive population growth decreases power. Although many studies have attempted to identify causal rare variants, few have reported novel associations. This has sometimes been interpreted to mean that rare variants make negligible contributions to complex trait heritability. Our work shows that RVATs are not robust to realistic human evolutionary forces, so general conclusions about the impact of rare variants on complex traits may be premature. PMID- 27197207 TI - Identification of the long, edited dsRNAome of LPS-stimulated immune cells. AB - Endogenous double-stranded RNA (dsRNA) must be intricately regulated in mammals to prevent aberrant activation of host inflammatory pathways by cytosolic dsRNA binding proteins. Here, we define the long, endogenous dsRNA repertoire in mammalian macrophages and monocytes during the inflammatory response to bacterial lipopolysaccharide. Hyperediting by adenosine deaminases that act on RNA (ADAR) enzymes was quantified over time using RNA-seq data from activated mouse macrophages to identify 342 Editing Enriched Regions (EERs), indicative of highly structured dsRNA. Analysis of publicly available data sets for samples of human peripheral blood monocytes resulted in discovery of 3438 EERs in the human transcriptome. Human EERs had predicted secondary structures that were significantly more stable than those of mouse EERs and were located primarily in introns, whereas nearly all mouse EERs were in 3' UTRs. Seventy-four mouse EER associated genes contained an EER in the orthologous human gene, although nucleotide sequence and position were only rarely conserved. Among these conserved EER-associated genes were several TNF alpha-signaling genes, including Sppl2a and Tnfrsf1b, important for processing and recognition of TNF alpha, respectively. Using publicly available data and experimental validation, we found that a significant proportion of EERs accumulated in the nucleus, a strategy that may prevent aberrant activation of proinflammatory cascades in the cytoplasm. The observation of many ADAR-edited dsRNAs in mammalian immune cells, a subset of which are in orthologous genes of mouse and human, suggests a conserved role for these structured regions. PMID- 27197208 TI - Interactions between pluripotency factors specify cis-regulation in embryonic stem cells. AB - We investigated how interactions between pluripotency transcription factors (TFs) affect cis-regulation. We created hundreds of synthetic cis-regulatory elements (CREs) comprised of combinations of binding sites for pluripotency TFs and measured their expression in mouse embryonic stem (ES) cells. A thermodynamic model that incorporates interactions between TFs explains a large portion (72%) of the variance in expression of these CREs. These interactions include three favorable heterotypic interactions between TFs. The model also predicts an unfavorable homotypic interaction between TFs, helping to explain the observation that homotypic chains of binding sites express at low levels. We further investigated the expression driven by CREs comprised of homotypic chains of KLF4 binding sites. Our results suggest that KLF homologs make unique contributions to regulation by these CREs. We conclude that a specific set of interactions between pluripotency TFs plays a large role in setting the levels of expression driven by CREs in ES cells. PMID- 27197209 TI - Evidence for the fixation of gene duplications by positive selection in Drosophila. AB - Gene duplications play a key role in the emergence of novel traits and in adaptation. But despite their centrality to evolutionary processes, it is still largely unknown how new gene duplicates are initially fixed within populations and later maintained in genomes. Long-standing debates on the evolution of gene duplications could be settled by determining the relative importance of genetic drift vs. positive selection in the fixation of new gene duplicates. Using the Drosophila Global Diversity Lines (GDL), we have combined genome-wide SNP polymorphism data with a novel set of copy number variant calls and gene expression profiles to characterize the polymorphic phase of new genes. We found that approximately half of the roughly 500 new complete gene duplications segregating in the GDL lead to significant increases in the expression levels of the duplicated genes and that these duplications are more likely to be found at lower frequencies, suggesting a negative impact on fitness. However, we also found that six of the nine gene duplications that are fixed or close to fixation in at least one of the five populations in our study show signs of being under positive selection, and that these duplications are likely beneficial because of dosage effects, with a possible role for additional mutations in two duplications. Our work suggests that in Drosophila, theoretical models that posit that gene duplications are immediately beneficial and fixed by positive selection are most relevant to explain the long-term evolution of gene duplications in this species. PMID- 27197210 TI - The mRNA-bound proteome of the early fly embryo. AB - Early embryogenesis is characterized by the maternal to zygotic transition (MZT), in which maternally deposited messenger RNAs are degraded while zygotic transcription begins. Before the MZT, post-transcriptional gene regulation by RNA binding proteins (RBPs) is the dominant force in embryo patterning. We used two mRNA interactome capture methods to identify RBPs bound to polyadenylated transcripts within the first 2 h of Drosophila melanogaster embryogenesis. We identified a high-confidence set of 476 putative RBPs and confirmed RNA-binding activities for most of 24 tested candidates. Most proteins in the interactome are known RBPs or harbor canonical RBP features, but 99 exhibited previously uncharacterized RNA-binding activity. mRNA-bound RBPs and TFs exhibit distinct expression dynamics, in which the newly identified RBPs dominate the first 2 h of embryonic development. Integrating our resource with in situ hybridization data from existing databases showed that mRNAs encoding RBPs are enriched in posterior regions of the early embryo, suggesting their general importance in posterior patterning and germ cell maturation. PMID- 27197212 TI - Evolutionary assembly patterns of prokaryotic genomes. AB - Evolutionary innovation must occur in the context of some genomic background, which limits available evolutionary paths. For example, protein evolution by sequence substitution is constrained by epistasis between residues. In prokaryotes, evolutionary innovation frequently happens by macrogenomic events such as horizontal gene transfer (HGT). Previous work has suggested that HGT can be influenced by ancestral genomic content, yet the extent of such gene-level constraints has not yet been systematically characterized. Here, we evaluated the evolutionary impact of such constraints in prokaryotes, using probabilistic ancestral reconstructions from 634 extant prokaryotic genomes and a novel framework for detecting evolutionary constraints on HGT events. We identified 8228 directional dependencies between genes and demonstrated that many such dependencies reflect known functional relationships, including for example, evolutionary dependencies of the photosynthetic enzyme RuBisCO. Modeling all dependencies as a network, we adapted an approach from graph theory to establish chronological precedence in the acquisition of different genomic functions. Specifically, we demonstrated that specific functions tend to be gained sequentially, suggesting that evolution in prokaryotes is governed by functional assembly patterns. Finally, we showed that these dependencies are universal rather than clade-specific and are often sufficient for predicting whether or not a given ancestral genome will acquire specific genes. Combined, our results indicate that evolutionary innovation via HGT is profoundly constrained by epistasis and historical contingency, similar to the evolution of proteins and phenotypic characters, and suggest that the emergence of specific metabolic and pathological phenotypes in prokaryotes can be predictable from current genomes. PMID- 27197211 TI - Divergence of a conserved elongation factor and transcription regulation in budding and fission yeast. AB - Complex regulation of gene expression in mammals has evolved from simpler eukaryotic systems, yet the mechanistic features of this evolution remain elusive. Here, we compared the transcriptional landscapes of the distantly related budding and fission yeast. We adapted the Precision Run-On sequencing (PRO-seq) approach to map the positions of RNA polymerase active sites genome wide in Schizosaccharomyces pombe and Saccharomyces cerevisiae. Additionally, we mapped preferred sites of transcription initiation in each organism using PRO cap. Unexpectedly, we identify a pause in early elongation, specific to S. pombe, that requires the conserved elongation factor subunit Spt4 and resembles promoter proximal pausing in metazoans. PRO-seq profiles in strains lacking Spt4 reveal globally elevated levels of transcribing RNA Polymerase II (Pol II) within genes in both species. Messenger RNA abundance, however, does not reflect the increases in Pol II density, indicating a global reduction in elongation rate. Together, our results provide the first base-pair resolution map of transcription elongation in S. pombe and identify divergent roles for Spt4 in controlling elongation in budding and fission yeast. PMID- 27197213 TI - SMASH, a fragmentation and sequencing method for genomic copy number analysis. AB - Copy number variants (CNVs) underlie a significant amount of genetic diversity and disease. CNVs can be detected by a number of means, including chromosomal microarray analysis (CMA) and whole-genome sequencing (WGS), but these approaches suffer from either limited resolution (CMA) or are highly expensive for routine screening (both CMA and WGS). As an alternative, we have developed a next generation sequencing-based method for CNV analysis termed SMASH, for short multiply aggregated sequence homologies. SMASH utilizes random fragmentation of input genomic DNA to create chimeric sequence reads, from which multiple mappable tags can be parsed using maximal almost-unique matches (MAMs). The SMASH tags are then binned and segmented, generating a profile of genomic copy number at the desired resolution. Because fewer reads are necessary relative to WGS to give accurate CNV data, SMASH libraries can be highly multiplexed, allowing large numbers of individuals to be analyzed at low cost. Increased genomic resolution can be achieved by sequencing to higher depth. PMID- 27197214 TI - Impact of the X Chromosome and sex on regulatory variation. AB - The X Chromosome, with its unique mode of inheritance, contributes to differences between the sexes at a molecular level, including sex-specific gene expression and sex-specific impact of genetic variation. Improving our understanding of these differences offers to elucidate the molecular mechanisms underlying sex specific traits and diseases. However, to date, most studies have either ignored the X Chromosome or had insufficient power to test for the sex-specific impact of genetic variation. By analyzing whole blood transcriptomes of 922 individuals, we have conducted the first large-scale, genome-wide analysis of the impact of both sex and genetic variation on patterns of gene expression, including comparison between the X Chromosome and autosomes. We identified a depletion of expression quantitative trait loci (eQTL) on the X Chromosome, especially among genes under high selective constraint. In contrast, we discovered an enrichment of sex specific regulatory variants on the X Chromosome. To resolve the molecular mechanisms underlying such effects, we generated chromatin accessibility data through ATAC-sequencing to connect sex-specific chromatin accessibility to sex specific patterns of expression and regulatory variation. As sex-specific regulatory variants discovered in our study can inform sex differences in heritable disease prevalence, we integrated our data with genome-wide association study data for multiple immune traits identifying several traits with significant sex biases in genetic susceptibilities. Together, our study provides genome-wide insight into how genetic variation, the X Chromosome, and sex shape human gene regulation and disease. PMID- 27197215 TI - Large-scale analysis of genome and transcriptome alterations in multiple tumors unveils novel cancer-relevant splicing networks. AB - Alternative splicing is regulated by multiple RNA-binding proteins and influences the expression of most eukaryotic genes. However, the role of this process in human disease, and particularly in cancer, is only starting to be unveiled. We systematically analyzed mutation, copy number, and gene expression patterns of 1348 RNA-binding protein (RBP) genes in 11 solid tumor types, together with alternative splicing changes in these tumors and the enrichment of binding motifs in the alternatively spliced sequences. Our comprehensive study reveals widespread alterations in the expression of RBP genes, as well as novel mutations and copy number variations in association with multiple alternative splicing changes in cancer drivers and oncogenic pathways. Remarkably, the altered splicing patterns in several tumor types recapitulate those of undifferentiated cells. These patterns are predicted to be mainly controlled by MBNL1 and involve multiple cancer drivers, including the mitotic gene NUMA1 We show that NUMA1 alternative splicing induces enhanced cell proliferation and centrosome amplification in nontumorigenic mammary epithelial cells. Our study uncovers novel splicing networks that potentially contribute to cancer development and progression. PMID- 27197216 TI - Venus flytrap carnivorous lifestyle builds on herbivore defense strategies. AB - Although the concept of botanical carnivory has been known since Darwin's time, the molecular mechanisms that allow animal feeding remain unknown, primarily due to a complete lack of genomic information. Here, we show that the transcriptomic landscape of the Dionaea trap is dramatically shifted toward signal transduction and nutrient transport upon insect feeding, with touch hormone signaling and protein secretion prevailing. At the same time, a massive induction of general defense responses is accompanied by the repression of cell death-related genes/processes. We hypothesize that the carnivory syndrome of Dionaea evolved by exaptation of ancient defense pathways, replacing cell death with nutrient acquisition. PMID- 27197217 TI - A hot L1 retrotransposon evades somatic repression and initiates human colorectal cancer. AB - Although human LINE-1 (L1) elements are actively mobilized in many cancers, a role for somatic L1 retrotransposition in tumor initiation has not been conclusively demonstrated. Here, we identify a novel somatic L1 insertion in the APC tumor suppressor gene that provided us with a unique opportunity to determine whether such insertions can actually initiate colorectal cancer (CRC), and if so, how this might occur. Our data support a model whereby a hot L1 source element on Chromosome 17 of the patient's genome evaded somatic repression in normal colon tissues and thereby initiated CRC by mutating the APC gene. This insertion worked together with a point mutation in the second APC allele to initiate tumorigenesis through the classic two-hit CRC pathway. We also show that L1 source profiles vary considerably depending on the ancestry of an individual, and that population specific hot L1 elements represent a novel form of cancer risk. PMID- 27197218 TI - Control of fluxes in metabolic networks. AB - Understanding the control of large-scale metabolic networks is central to biology and medicine. However, existing approaches either require specifying a cellular objective or can only be used for small networks. We introduce new coupling types describing the relations between reaction activities, and develop an efficient computational framework, which does not require any cellular objective for systematic studies of large-scale metabolism. We identify the driver reactions facilitating control of 23 metabolic networks from all kingdoms of life. We find that unicellular organisms require a smaller degree of control than multicellular organisms. Driver reactions are under complex cellular regulation in Escherichia coli, indicating their preeminent role in facilitating cellular control. In human cancer cells, driver reactions play pivotal roles in malignancy and represent potential therapeutic targets. The developed framework helps us gain insights into regulatory principles of diseases and facilitates design of engineering strategies at the interface of gene regulation, signaling, and metabolism. PMID- 27197220 TI - Distinct transcription factor complexes act on a permissive chromatin landscape to establish regionalized gene expression in CNS stem cells. AB - Spatially distinct gene expression profiles in neural stem cells (NSCs) are a prerequisite to the formation of neuronal diversity, but how these arise from the regulatory interactions between chromatin accessibility and transcription factor activity has remained unclear. Here, we demonstrate that, despite their distinct gene expression profiles, NSCs of the mouse cortex and spinal cord share the majority of their DNase I hypersensitive sites (DHSs). Regardless of this similarity, domain-specific gene expression is highly correlated with the relative accessibility of associated DHSs, as determined by sequence read density. Notably, the binding pattern of the general NSC transcription factor SOX2 is also largely cell type specific and coincides with an enrichment of LHX2 motifs in the cortex and HOXA9 motifs in the spinal cord. Interestingly, in a zebrafish reporter gene system, these motifs were critical determinants of patterned gene expression along the rostral-caudal axis. Our findings establish a predictive model for patterned NSC gene expression, whereby domain-specific expression of LHX2 and HOX proteins act on their target motifs within commonly accessible cis-regulatory regions to specify SOX2 binding. In turn, this binding correlates strongly with these DHSs relative accessibility-a robust predictor of neighboring gene expression. PMID- 27197219 TI - The interaction of PRC2 with RNA or chromatin is mutually antagonistic. AB - Polycomb repressive complex 2 (PRC2) modifies chromatin to maintain genes in a repressed state during development. PRC2 is primarily associated with CpG islands at repressed genes and also possesses RNA binding activity. However, the RNAs that bind PRC2 in cells, the subunits that mediate these interactions, and the role of RNA in PRC2 recruitment to chromatin all remain unclear. By performing iCLIP for PRC2 in comparison with other RNA binding proteins, we show here that PRC2 binds nascent RNA at essentially all active genes. Although interacting with RNA promiscuously, PRC2 binding is enriched at specific locations within RNAs, primarily exon-intron boundaries and the 3' UTR. Deletion of other PRC2 subunits reveals that SUZ12 is sufficient to establish this RNA binding profile. Contrary to prevailing models, we also demonstrate that the interaction of PRC2 with RNA or chromatin is mutually antagonistic in cells and in vitro. RNA degradation in cells triggers PRC2 recruitment to CpG islands at active genes. Correspondingly, the release of PRC2 from chromatin in cells increases RNA binding. Consistent with this, RNA and nucleosomes compete for PRC2 binding in vitro. We propose that RNA prevents PRC2 recruitment to chromatin at active genes and that mutual antagonism between RNA and chromatin underlies the pattern of PRC2 chromatin association across the genome. PMID- 27197221 TI - A novel nuclear genetic code alteration in yeasts and the evolution of codon reassignment in eukaryotes. AB - The genetic code is the cellular translation table for the conversion of nucleotide sequences into amino acid sequences. Changes to the meaning of sense codons would introduce errors into almost every translated message and are expected to be highly detrimental. However, reassignment of single or multiple codons in mitochondria and nuclear genomes, although extremely rare, demonstrates that the code can evolve. Several models for the mechanism of alteration of nuclear genetic codes have been proposed (including "codon capture," "genome streamlining," and "ambiguous intermediate" theories), but with little resolution. Here, we report a novel sense codon reassignment in Pachysolen tannophilus, a yeast related to the Pichiaceae. By generating proteomics data and using tRNA sequence comparisons, we show that Pachysolen translates CUG codons as alanine and not as the more usual leucine. The Pachysolen tRNACAG is an anticodon mutated tRNA(Ala) containing all major alanine tRNA recognition sites. The polyphyly of the CUG-decoding tRNAs in yeasts is best explained by a tRNA loss driven codon reassignment mechanism. Loss of the CUG-tRNA in the ancient yeast is followed by gradual decrease of respective codons and subsequent codon capture by tRNAs whose anticodon is not part of the aminoacyl-tRNA synthetase recognition region. Our hypothesis applies to all nuclear genetic code alterations and provides several testable predictions. We anticipate more codon reassignments to be uncovered in existing and upcoming genome projects. PMID- 27197222 TI - A flexible method for estimating the fraction of fitness influencing mutations from large sequencing data sets. AB - A continuing challenge in the analysis of massively large sequencing data sets is quantifying and interpreting non-neutrally evolving mutations. Here, we describe a flexible and robust approach based on the site frequency spectrum to estimate the fraction of deleterious and adaptive variants from large-scale sequencing data sets. We applied our method to approximately 1 million single nucleotide variants (SNVs) identified in high-coverage exome sequences of 6515 individuals. We estimate that the fraction of deleterious nonsynonymous SNVs is higher than previously reported; quantify the effects of genomic context, codon bias, chromatin accessibility, and number of protein-protein interactions on deleterious protein-coding SNVs; and identify pathways and networks that have likely been influenced by positive selection. Furthermore, we show that the fraction of deleterious nonsynonymous SNVs is significantly higher for Mendelian versus complex disease loci and in exons harboring dominant versus recessive Mendelian mutations. In summary, as genome-scale sequencing data accumulate in progressively larger sample sizes, our method will enable increasingly high resolution inferences into the characteristics and determinants of non-neutral variation. PMID- 27197223 TI - Quantitative insertion-site sequencing (QIseq) for high throughput phenotyping of transposon mutants. AB - Genetic screening using random transposon insertions has been a powerful tool for uncovering biology in prokaryotes, where whole-genome saturating screens have been performed in multiple organisms. In eukaryotes, such screens have proven more problematic, in part because of the lack of a sensitive and robust system for identifying transposon insertion sites. We here describe quantitative insertion-site sequencing, or QIseq, which uses custom library preparation and Illumina sequencing technology and is able to identify insertion sites from both the 5' and 3' ends of the transposon, providing an inbuilt level of validation. The approach was developed using piggyBac mutants in the human malaria parasite Plasmodium falciparum but should be applicable to many other eukaryotic genomes. QIseq proved accurate, confirming known sites in >100 mutants, and sensitive, identifying and monitoring sites over a >10,000-fold dynamic range of sequence counts. Applying QIseq to uncloned parasites shortly after transfections revealed multiple insertions in mixed populations and suggests that >4000 independent mutants could be generated from relatively modest scales of transfection, providing a clear pathway to genome-scale screens in P. falciparum QIseq was also used to monitor the growth of pools of previously cloned mutants and reproducibly differentiated between deleterious and neutral mutations in competitive growth. Among the mutants with fitness defects was a mutant with a piggyBac insertion immediately upstream of the kelch protein K13 gene associated with artemisinin resistance, implying mutants in this gene may have competitive fitness costs. QIseq has the potential to enable the scale-up of piggyBac-mediated genetics across multiple eukaryotic systems. PMID- 27197224 TI - Basset: learning the regulatory code of the accessible genome with deep convolutional neural networks. AB - The complex language of eukaryotic gene expression remains incompletely understood. Despite the importance suggested by many noncoding variants statistically associated with human disease, nearly all such variants have unknown mechanisms. Here, we address this challenge using an approach based on a recent machine learning advance-deep convolutional neural networks (CNNs). We introduce the open source package Basset to apply CNNs to learn the functional activity of DNA sequences from genomics data. We trained Basset on a compendium of accessible genomic sites mapped in 164 cell types by DNase-seq, and demonstrate greater predictive accuracy than previous methods. Basset predictions for the change in accessibility between variant alleles were far greater for Genome-wide association study (GWAS) SNPs that are likely to be causal relative to nearby SNPs in linkage disequilibrium with them. With Basset, a researcher can perform a single sequencing assay in their cell type of interest and simultaneously learn that cell's chromatin accessibility code and annotate every mutation in the genome with its influence on present accessibility and latent potential for accessibility. Thus, Basset offers a powerful computational approach to annotate and interpret the noncoding genome. PMID- 27197227 TI - Commentary on Alfred G. Knudson, Jr.: "Hereditary Cancer, Oncogenes, and Antioncogenes". PMID- 27197228 TI - Commentary on Folkman: "How Is Blood Vessel Growth Regulated in Normal and Neoplastic Tissue?". AB - Angiogenesis is a prerequisite for tumor growth and metastatic progression. The discovery of the first specific angiogenic cytokine, VEGF, in 1989 paved the way for the clinical approval of the first antiangiogenic tumor drug 15 years later. This brief commentary highlights and puts into historical perspective the 1985 G.H.A. Clowes Memorial Award Lecture delivered by Dr. Judah Folkman. Thirty years later, this award lecture is a lively testimony of the visionary mind of Dr. Folkman, whose legacy continues to inspire contemporary angiogenesis research. Cancer Res; 76(10); 2854-6. (c)2016 AACRSee related article by Folkman J, Cancer Res 1986;46:467-73. PMID- 27197225 TI - Specific down-regulation of spermatogenesis genes targeted by 22G RNAs in hybrid sterile males associated with an X-Chromosome introgression. AB - Hybrid incompatibility (HI) prevents gene flow between species, thus lying at the heart of speciation genetics. One of the most common HIs is male sterility. Two superficially contradictory observations exist for hybrid male sterility. First, an introgression on the X Chromosome is more likely to produce male sterility than on autosome (so-called large-X theory); second, spermatogenesis genes are enriched on the autosomes but depleted on the X Chromosome (demasculinization of X Chromosome). Analysis of gene expression in Drosophila hybrids suggests a genetic interaction between the X Chromosome and autosomes that is essential for male fertility. However, the prevalence of such an interaction and its underlying mechanism remain largely unknown. Here we examine the interaction in nematode species by contrasting the expression of both coding genes and transposable elements (TEs) between hybrid sterile males and its parental nematode males. We use two lines of hybrid sterile males, each carrying an independent introgression fragment from Caenorhabditis briggsae X Chromosome in an otherwise Caenorhabditis nigoni background, which demonstrate similar defects in spermatogenesis. We observe a similar pattern of down-regulated genes that are specific for spermatogenesis between the two hybrids. Importantly, the down-regulated genes caused by the X Chromosome introgressions show a significant enrichment on the autosomes, supporting an epistatic interaction between the X Chromosome and autosomes. We investigate the underlying mechanism of the interaction by measuring small RNAs and find that a subset of 22G RNAs specifically targeting the down-regulated spermatogenesis genes is significantly up-regulated in hybrids, suggesting that perturbation of small RNA-mediated regulation may contribute to the X-autosome interaction. PMID- 27197229 TI - The Widening Sphere of Influence of HOXB7 in Solid Tumors. AB - Strong lines of evidence have established a critical role for the homeodomain protein HOXB7 in cancer. Specifically, molecular and cellular studies have demonstrated that HOXB7 is a master regulatory gene, capable of orchestrating a variety of target molecules, resulting in the activation of several oncogenic pathways. HOXB7 overexpression correlates with clinical progression and poor outcome of cancer patients. Specific inhibition of HOXB7 is particularly relevant in cancers still lacking effective therapies, such as tamoxifen-resistant breast cancer and melanoma. Mechanistic studies are providing additional targets of therapy, and biomarker studies are further establishing its importance in early diagnosis and prognosis. Cancer Res; 76(10); 2857-62. (c)2016 AACR. PMID- 27197230 TI - Hematopoietic Age at Onset of Triple-Negative Breast Cancer Dictates Disease Aggressiveness and Progression. AB - Triple-negative breast cancer (TNBC) is considered an early onset subtype of breast cancer that carries with it a poorer prognosis in young rather than older women for reasons that remain poorly understood. Hematopoiesis in the bone marrow becomes altered with age and may therefore affect the composition of tumor infiltrating hematopoietic cells and subsequent tumor progression. In this study, we investigated how age- and tumor-dependent changes to bone marrow-derived hematopoietic cells impact TNBC progression. Using multiple mouse models of TNBC tumorigenesis and metastasis, we found that a specific population of bone marrow cells (BMC) upregulated CSF-1R and secreted the growth factor granulin to support stromal activation and robust tumor growth in young mice. However, the same cell population in old mice expressed low levels of CSF1R and granulin and failed to promote tumor outgrowth, suggesting that age influences the tumorigenic capacity of BMCs in response to tumor-associated signals. Importantly, BMCs from young mice were sufficient to activate a tumor-supportive microenvironment and induce tumor progression in old mice. These results indicate that hematopoietic age is an important determinant of TNBC aggressiveness and provide rationale for investigating age-stratified therapies designed to prevent the protumorigenic effects of activated BMCs. Cancer Res; 76(10); 2932-43. (c)2016 AACR. PMID- 27197232 TI - p53 Loss in MYC-Driven Neuroblastoma Leads to Metabolic Adaptations Supporting Radioresistance. AB - Neuroblastoma is the most common childhood extracranial solid tumor. In high-risk cases, many of which are characterized by amplification of MYCN, outcome remains poor. Mutations in the p53 (TP53) tumor suppressor are rare at diagnosis, but evidence suggests that p53 function is often impaired in relapsed, treatment resistant disease. To address the role of p53 loss of function in the development and pathogenesis of high-risk neuroblastoma, we generated a MYCN-driven genetically engineered mouse model in which the tamoxifen-inducible p53ER(TAM) fusion protein was expressed from a knock-in allele (Th-MYCN/Trp53(KI)). We observed no significant differences in tumor-free survival between Th-MYCN mice heterozygous for Trp53(KI) (n = 188) and Th-MYCN mice with wild-type p53 (n = 101). Conversely, the survival of Th-MYCN/Trp53(KI/KI) mice lacking functional p53 (n = 60) was greatly reduced. We found that Th-MYCN/Trp53(KI/KI) tumors were resistant to ionizing radiation (IR), as expected. However, restoration of functional p53ER(TAM) reinstated sensitivity to IR in only 50% of Th MYCN/Trp53(KI/KI) tumors, indicating the acquisition of additional resistance mechanisms. Gene expression and metabolic analyses indicated that the principal acquired mechanism of resistance to IR in the absence of functional p53 was metabolic adaptation in response to chronic oxidative stress. Tumors exhibited increased antioxidant metabolites and upregulation of glutathione S-transferase pathway genes, including Gstp1 and Gstz1, which are associated with poor outcome in human neuroblastoma. Accordingly, glutathione depletion by buthionine sulfoximine together with restoration of p53 activity resensitized tumors to IR. Our findings highlight the complex pathways operating in relapsed neuroblastomas and the need for combination therapies that target the diverse resistance mechanisms at play. Cancer Res; 76(10); 3025-35. (c)2016 AACR. PMID- 27197234 TI - Heterogeneity in Tumors and Resistance to EGFR TKI Therapy-Letter. PMID- 27197231 TI - Caspase-9b Interacts Directly with cIAP1 to Drive Agonist-Independent Activation of NF-kappaB and Lung Tumorigenesis. AB - Alternate RNA processing of caspase-9 generates the splice variants caspase 9a (C9a) and caspase 9b (C9b). C9b lacks a domain present in C9a, revealing a tumorigenic function that drives the phenotype of non-small cell lung cancer (NSCLC) cells. In this study, we elucidated the mechanistic underpinnings of the malignant character of this splice isoform. In NSCLC cells, C9b expression correlated with activation of the canonical arm of the NF-kappaB pathway, a major pathway linked to the NSCLC tumorigenesis. Mechanistic investigations revealed that C9b activates this pathway via direct interaction with cellular inhibitor of apoptosis 1 (cIAP1) and subsequent induction of the E3 ligase activity of this IAP family member. The C9b:cIAP1 interaction occurred via the BIR3 domain of cIAP1 and the IAP-binding motif of C9b, but did not require proteolytic cleavage of C9b. This protein:protein interaction was essential for C9b to promote viability and malignant growth of NSCLC cells in vitro and in vivo, broadly translating to diverse NSCLC oncogenotypes. Overall, our findings identified a novel point for therapeutic invention in NSCLC that may be tractable to small molecule inhibitors, as a new point to broadly address this widespread deadly disease. Cancer Res; 76(10); 2977-89. (c)2016 AACR. PMID- 27197233 TI - Loss of Tet1-Associated 5-Hydroxymethylcytosine Is Concomitant with Aberrant Promoter Hypermethylation in Liver Cancer. AB - Aberrant hypermethylation of CpG islands (CGI) in human tumors occurs predominantly at repressed genes in the host tissue, but the preceding events driving this phenomenon are poorly understood. In this study, we temporally tracked epigenetic and transcriptomic perturbations that occur in a mouse model of liver carcinogenesis. Hypermethylated CGI events in the model were predicted by enrichment of the DNA modification 5-hydroxymethylcytosine (5hmC) and the histone H3 modification H3K27me3 at silenced promoters in the host tissue. During cancer progression, selected CGIs underwent hypo-hydroxymethylation prior to hypermethylation, while retaining H3K27me3. In livers from mice deficient in Tet1, a tumor suppressor involved in cytosine demethylation, we observed a similar loss of promoter core 5hmC, suggesting that reduced Tet1 activity at CGI may contribute to epigenetic dysregulation during hepatocarcinogenesis. Consistent with this possibility, mouse liver tumors exhibited reduced Tet1 protein levels. Similar to humans, DNA methylation changes at CGI in mice did not appear to be direct drivers of hepatocellular carcinoma progression, rather, dynamic changes in H3K27me3 promoter deposition correlated strongly with tumor specific activation and repression of transcription. Overall, our results suggest that loss of promoter-associated 5hmC in liver tumors licenses reprograming of DNA methylation at silent CGI during progression. Cancer Res; 76(10); 3097-108. (c)2016 AACR. PMID- 27197235 TI - Heterogeneity in Tumors and Resistance to EGFR TKI Therapy-Response. PMID- 27197236 TI - The tumor-suppressive small GTPase DiRas1 binds the noncanonical guanine nucleotide exchange factor SmgGDS and antagonizes SmgGDS interactions with oncogenic small GTPases. PMID- 27197239 TI - Commentary on Folkman: "Tumor Angiogenesis Factor". PMID- 27197237 TI - Pattern recognition protein binds to lipopolysaccharide and beta-1,3-glucan and activates shrimp prophenoloxidase system. PMID- 27197240 TI - Tumor Cell Invasion-Not All Barriers Are Created Equal. AB - The importance of invasion in the complex process of metastasis, although now well established, has been studied with increasing molecular detail due to the development of robust in vitro experimental assays. In this issue of Cancer Research, we highlight a paper published by George Poste and colleagues that compared and contrasted several different invasion assays. The authors concluded that various barriers impose different selective pressures and that simply enriching for invasive ability did not necessarily translate into greater metastasis efficiency. Although perhaps obvious now, these findings were surprising when they were published. Certainly, the data highlight the importance of tumor cell-microenvironment interactions and the necessity to interpret experiments taking the context into consideration. Cancer Res; 76(7); 1675-6. (c)2016 AACRSee related article by Poste et al., Cancer Res 1980;40:1636-44. PMID- 27197241 TI - Correction: Lupeol Suppresses Cisplatin-Induced Nuclear Factor-kappaB Activation in Head and Neck Squamous Cell Carcinoma and Inhibits Local Invasion and Nodal Metastasis in an Orthotopic Nude Mouse Model. PMID- 27197242 TI - Zygotes segregate entire parental genomes in distinct blastomere lineages causing cleavage-stage chimerism and mixoploidy. AB - Dramatic genome dynamics, such as chromosome instability, contribute to the remarkable genomic heterogeneity among the blastomeres comprising a single embryo during human preimplantation development. This heterogeneity, when compatible with life, manifests as constitutional mosaicism, chimerism, and mixoploidy in live-born individuals. Chimerism and mixoploidy are defined by the presence of cell lineages with different parental genomes or different ploidy states in a single individual, respectively. Our knowledge of their mechanistic origin results from indirect observations, often when the cell lineages have been subject to rigorous selective pressure during development. Here, we applied haplarithmisis to infer the haplotypes and the copy number of parental genomes in 116 single blastomeres comprising entire preimplantation bovine embryos (n = 23) following in vitro fertilization. We not only demonstrate that chromosome instability is conserved between bovine and human cleavage embryos, but we also discovered that zygotes can spontaneously segregate entire parental genomes into different cell lineages during the first post-zygotic cleavage division. Parental genome segregation was not exclusively triggered by abnormal fertilizations leading to triploid zygotes, but also normally fertilized zygotes can spontaneously segregate entire parental genomes into different cell lineages during cleavage of the zygote. We coin the term "heterogoneic division" to indicate the events leading to noncanonical zygotic cytokinesis, segregating the parental genomes into distinct cell lineages. Persistence of those cell lines during development is a likely cause of chimerism and mixoploidy in mammals. PMID- 27197244 TI - Corrigendum: Model-based analyses of whole-genome data reveal a complex evolutionary history involving archaic introgression in Central African Pygmies. PMID- 27197243 TI - Improved definition of the mouse transcriptome via targeted RNA sequencing. AB - Targeted RNA sequencing (CaptureSeq) uses oligonucleotide probes to capture RNAs for sequencing, providing enriched read coverage, accurate measurement of gene expression, and quantitative expression data. We applied CaptureSeq to refine transcript annotations in the current murine GRCm38 assembly. More than 23,000 regions corresponding to putative or annotated long noncoding RNAs (lncRNAs) and 154,281 known splicing junction sites were selected for targeted sequencing across five mouse tissues and three brain subregions. The results illustrate that the mouse transcriptome is considerably more complex than previously thought. We assemble more complete transcript isoforms than GENCODE, expand transcript boundaries, and connect interspersed islands of mapped reads. We describe a novel filtering pipeline that identifies previously unannotated but high-quality transcript isoforms. In this set, 911 GENCODE neighboring genes are condensed into 400 expanded gene models. Additionally, 594 GENCODE lncRNAs acquire an open reading frame (ORF) when their structure is extended with CaptureSeq. Finally, we validate our observations using current FANTOM and Mouse ENCODE resources. PMID- 27197245 TI - Corrigendum: Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells. PMID- 27197248 TI - Human Cancers Express a Mutator Phenotype: Hypothesis, Origin, and Consequences. AB - The mutator phenotype hypothesis was postulated more than 40 years ago. It was based on the multiple enzymatic steps required to precisely replicate the 6 billion bases in the human genome each time a normal cell divides. A reduction in this accuracy during tumor progression could be responsible for the striking heterogeneity of malignant cells within a tumor and for the rapidity by which cancers become resistant to therapy. Cancer Res; 76(8); 2057-9. (c)2016 AACRSee related article by Loeb et al. Cancer Res. 1974;34:2311-21. PMID- 27197249 TI - Jacob, Monod, the Lac Operon, and the PaJaMa Experiment-Gene Expression Circuitry Changing the Face of Cancer Research. PMID- 27197250 TI - The Role of Cholesterol in Cancer. AB - The roles played by cholesterol in cancer development and the potential of therapeutically targeting cholesterol homeostasis is a controversial area in the cancer community. Several epidemiologic studies report an association between cancer and serum cholesterol levels or statin use, while others suggest that there is not one. Furthermore, the Cancer Genome Atlas (TCGA) project using next generation sequencing has profiled the mutational status and expression levels of all the genes in diverse cancers, including those involved in cholesterol metabolism, providing correlative support for a role of the cholesterol pathway in cancer development. Finally, preclinical studies tend to more consistently support the role of cholesterol in cancer, with several demonstrating that cholesterol homeostasis genes can modulate development. Because of space limitations, this review provides selected examples of the epidemiologic, TCGA, and preclinical data, focusing on alterations in cholesterol homeostasis and its consequent effect on patient survival. In melanoma, this focused analysis demonstrated that enhanced expression of cholesterol synthesis genes was associated with decreased patient survival. Collectively, the studies in melanoma and other cancer types suggested a potential role of disrupted cholesterol homeostasis in cancer development but additional studies are needed to link population-based epidemiological data, the TCGA database results, and preclinical mechanistic evidence to concretely resolve this controversy. Cancer Res; 76(8); 2063-70. (c)2016 AACR. PMID- 27197251 TI - TALEN-Mediated Inactivation of PD-1 in Tumor-Reactive Lymphocytes Promotes Intratumoral T-cell Persistence and Rejection of Established Tumors. AB - Despite the promising efficacy of adoptive cell therapies (ACT) in melanoma, complete response rates remain relatively low and outcomes in other cancers are less impressive. The immunosuppressive nature of the tumor microenvironment and the expression of immune-inhibitory ligands, such as PD-L1/CD274 by the tumor and stroma are considered key factors limiting efficacy. The addition of checkpoint inhibitors (CPI) to ACT protocols bypasses some mechanisms of immunosuppression, but associated toxicities remain a significant concern. To overcome PD-L1 mediated immunosuppression and reduce CPI-associated toxicities, we used TALEN technology to render tumor-reactive T cells resistant to PD-1 signaling. Here, we demonstrate that inactivation of the PD-1 gene in melanoma-reactive CD8(+) T cells and in fibrosarcoma-reactive polyclonal T cells enhanced the persistence of PD-1 gene-modified T cells at the tumor site and increased tumor control. These results illustrate the feasibility and potency of approaches incorporating advanced gene-editing technologies into ACT protocols to silence immune checkpoints as a strategy to overcome locally active immune escape pathways. Cancer Res; 76(8); 2087-93. (c)2016 AACR. PMID- 27197252 TI - Inherent and Tumor-Driven Immune Tolerance in the Prostate Microenvironment Impairs Natural Killer Cell Antitumor Activity. AB - The field of immunotherapy for solid tumors, such as prostate cancer, has been recently focusing on therapies that can counter tumor-mediated immunosuppression. Precise quantification and characterization of the immune infiltrates in tumors is crucial to improve treatment efficacy. Natural killer (NK) cells, major components of the antitumor immune system, have never been isolated from prostate tumors, despite their suspected role in disease progression. Here, we examined the frequency, phenotype, and functions of NK cells infiltrating control and tumor prostate tissues. NK cell infiltrates in prostate tissues were mainly CD56 (NCAM1)-positive and displayed an unexpected immature, but activated, phenotype with low or no cytotoxic potential. Furthermore, we show that TGFbeta1 (TGFB1) is highly secreted into the prostate environment and partly mediates the immunosuppressive effects on NK cells. In addition to this basal level of immunotolerance to NK cells, the prostate environment became further resistant to NK cell-mediated immunity upon cancer cell infiltration. Coculture experiments revealed that prostate cancer cells induced the expression of inhibitory receptor (ILT2/LILRB1) and downregulated the expression of activating receptors NKp46 (NCR1), NKG2D (KLRK1), and CD16 (FCGR3) by NK cells, thus preventing their recognition of tumor cells. Notably, blood levels of NKp46 were also decreased in prostate cancer patients and were inversely correlated with levels of prostate specific antigen, the main prognostic factor in prostate cancer. Our study shows that a strong immunosuppressive environment impairs NK cell function at multiple levels in prostate cancer and provides a rationale for the design of therapies that restore NK cell efficiency in the prostate tumor microenvironment. Cancer Res; 76(8); 2153-65. (c)2016 AACR. PMID- 27197254 TI - Correction: Lens Epithelium-Derived Growth Factor Is an Hsp70-2 Regulated Guardian of Lysosomal Stability in Human Cancer. PMID- 27197253 TI - Immunoregulatory Protein B7-H3 Reprograms Glucose Metabolism in Cancer Cells by ROS-Mediated Stabilization of HIF1alpha. AB - B7-H3 is a member of B7 family of immunoregulatory transmembrane glycoproteins expressed by T cells. While B7-H3 overexpression is associated with poor outcomes in multiple cancers, it also has immune-independent roles outside T cells and its precise mechanistic contributions to cancer are unclear. In this study, we investigated the role of B7-H3 in metabolic reprogramming of cancer cells in vitro and in vivo We found that B7-H3 promoted the Warburg effect, evidenced by increased glucose uptake and lactate production in B7-H3-expressing cells. B7-H3 also increased the protein levels of HIF1alpha and its downstream targets, LDHA and PDK1, key enzymes in the glycolytic pathway. Furthermore, B7-H3 promoted reactive oxygen species-dependent stabilization of HIF1alpha by suppressing the activity of the stress-activated transcription factor Nrf2 and its target genes, including the antioxidants SOD1, SOD2, and PRX3. Metabolic imaging of human breast cancer xenografts in mice confirmed that B7-H3 enhanced tumor glucose uptake and tumor growth. Together, our results illuminate the critical immune independent contributions of B7-H3 to cancer metabolism, presenting a radically new perspective on B7 family immunoregulatory proteins in malignant progression. Cancer Res; 76(8); 2231-42. (c)2016 AACR. PMID- 27197256 TI - Strategic Combinations: The Future of Oncolytic Virotherapy with Reovirus. AB - The dominant cancer treatment modalities such as chemotherapy, radiotherapy, and even targeted kinase inhibitors and mAbs are limited by low efficacy, toxicity, and treatment-resistant tumor subclones. Oncolytic viral therapy offers a novel therapeutic strategy that has the potential to dramatically improve clinical outcomes. Reovirus, a double-stranded benign human RNA virus, is a leading candidate for therapeutic development and currently in phase III trials. Reovirus selectively targets transformed cells with activated Ras signaling pathways; Ras genes are some of the most frequently mutated oncogenes in human cancer and it is estimated that at least 30% of all human tumors exhibit aberrant Ras signaling. By targeting Ras-activated cells, reovirus can directly lyse cancer cells, disrupt tumor immunosuppressive mechanisms, reestablish multicellular immune surveillance, and generate robust antitumor responses. Reovirus therapy is currently being tested in combination with radiotherapy, chemotherapy, immunotherapy, and surgery. In this review, we discuss the current successes of these combinatorial therapeutic strategies and emphasize the importance of prioritizing combination oncolytic viral therapy as reovirus-based treatments progress in clinical development. Mol Cancer Ther; 15(5); 767-73. (c)2016 AACR. PMID- 27197257 TI - The Role of PGC1alpha in Cancer Metabolism and its Therapeutic Implications. AB - PGC1alpha is a transcription factor coactivator that influences a majority of cellular metabolic pathways. Abnormal expression of PGC1alpha is associated with several chronic diseases and, in recent years, it has been shown to be a critical controller of cancer development. PGC1alpha acts as a stress sensor in cancer cells and can be activated by nutrient deprivation, oxidative damage, and chemotherapy. It influences mitochondria respiration, reactive oxygen species defense system, and fatty acid metabolism by interacting with specific transcription factors. The characteristic traits of PGC1alpha in maintaining metabolic homeostasis promote cancer cell survival and tumor metastasis in harsh microenvironments. Not only does PGC1alpha act as a coactivator, but is also itself controlled by oncogenes and transcription factors. PGC1alpha and these molecules can form signaling axes that include PML/PGC1alpha/PPARalpha, MITF/PGC1alpha, and PGC1alpha/ERRalpha, which are important in regulating metabolic adaptation in specific cancer types. Some of these PGC1alpha-associated pathways are inherently activated in cancer cells, and others are induced by stress, which enable cancer cells to acquire resistance against therapy. Notably, certain therapeutic-resistant cancer cells are addicted to PGC1alpha-dependent metabolic activities. Suppression of PGC1alpha expression resensitizes these cells to therapeutic treatments, which implicates PGC1alpha as a promising target in cancer molecular classification and therapy. Mol Cancer Ther; 15(5); 774-82. (c)2016 AACR. PMID- 27197259 TI - The Impact of Nathan Mantel's "The Detection of Disease Clustering and a Generalized Regression Approach". PMID- 27197260 TI - PDT: What's Past Is Prologue. AB - Despite descriptions of light-mediated therapy in ancient texts and the discovery of photodynamic therapy (PDT) in the early 1900s, the landmark article in 1978 in Cancer Research by Dougherty and his colleagues at the Roswell Park Cancer Institute remains rightly viewed as the starting point for clinical PDT in modern medicine. As a large clinical series that explored many of the factors now viewed as critical determinates of PDT dose, efficacy, and toxicity, that study showed remarkable foresight, yet it also served to raise as many questions as it answered. Since its publication, PDT has been increasingly utilized in clinical practice for the treatment of both benign and malignant conditions, and many of their questions have yielded new technologies and areas of investigation, thus remaining highly relevant nearly 40 years after their initial asking. Moreover, continuing advances in our ability to measure physical properties such as absorbed light dose, photosensitizer concentration, tissue oxygen concentration, and singlet oxygen production in real-time may allow for adaptive modification of light delivery during PDT on a fine scale to optimize treatment response. Finally, combining molecularly targeted drugs and novel photosensitizers has the potential to improve further the therapeutic index and extend the spectrum of clinical PDT far beyond what was imagined when that sentinel manuscript was written. Cancer Res; 76(9); 2497-9. (c)2016 AACRSee related article by Dougherty et al., Cancer Res 1978;38:2628-35Visit the Cancer Research 75(th) Anniversary timeline. PMID- 27197262 TI - Carcinoma Cell Hyaluronan as a "Portable" Cancerized Prometastatic Microenvironment. AB - Hyaluronan (HA) is a structurally simple polysaccharide, but its ability to act as a template for organizing pericellular matrices and its regulated synthesis and degradation are key to initiating repair responses. Importantly, these HA functions are usurped by tumor cells to facilitate progression and metastasis. Recent advances have identified the functional complexities associated with the synthesis and degradation of HA-rich matrices. Three enzymes synthesize large HA polymers while multiple hyaluronidases or tissue free radicals degrade these into smaller bioactive fragments. A family of extracellular and cell-associated HA binding proteins/receptors translates the bioinformation encrypted in this complex polymer mixture to activate signaling networks required for cell survival, proliferation, and migration in an actively remodeling microenvironment. Changes in HA metabolism within both the peritumor stroma and parenchyma are linked to tumor initiation, progression, and poor clinical outcome. We review evidence that metastatic tumor cells must acquire the capability to autonomously synthesize, assemble, and process their own "portable" HA-rich microenvironments to survive in the circulation, metastasize to ectopic sites, and escape therapeutic intervention. Strategies to disrupt the HA machinery of primary tumor and circulating tumor cells may enhance the effectiveness of current conventional and targeted therapies. Cancer Res; 76(9); 2507-12. (c)2016 AACR. PMID- 27197261 TI - Mitochondrial Sirtuins in Cancer: Emerging Roles and Therapeutic Potential. AB - The past few decades have witnessed a furious attention of scientific community toward identifying novel molecular factors and targets that could be exploited for drug development for cancer management. One such factor is the sirtuin (SIRT) family of nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylases. The role of SIRTs in cancer is extremely complex, with dichotomous functions depending on cell contexts. Mammalian SIRTs (SIRT1-7) differ in their cellular localization and biologic functions. Among these, SIRT -3, -4, and -5 are located in the mitochondria and are being carefully investigated. These mitochondrial SIRTs (mtSIRT) regulate multiple cellular and physiologic processes, including cell cycle, gene expression, cell viability, stress response, metabolism, and energy homeostasis. Recent research suggests that mtSIRTs influence tumors by regulating the metabolic state of the cell. Although the research on the role of mtSIRTs in cancer is still in its infancy, studies have suggested tumor suppressor as well as tumor promoter roles for them. This review is focused on discussing up-to-date information about the roles and functional relevance of mtSIRTs (SIRT -3, -4, -5) in cancers. We have also provided a critical discussion and our perspective on their dual roles, as tumor promoter versus tumor suppressor, in cancer. Cancer Res; 76(9); 2500-6. (c)2016 AACR. PMID- 27197263 TI - Feasibility of Telomerase-Specific Adoptive T-cell Therapy for B-cell Chronic Lymphocytic Leukemia and Solid Malignancies. AB - Telomerase (TERT) is overexpressed in 80% to 90% of primary tumors and contributes to sustaining the transformed phenotype. The identification of several TERT epitopes in tumor cells has elevated the status of TERT as a potential universal target for selective and broad adoptive immunotherapy. TERT specific cytotoxic T lymphocytes (CTL) have been detected in the peripheral blood of B-cell chronic lymphocytic leukemia (B-CLL) patients, but display low functional avidity, which limits their clinical utility in adoptive cell transfer approaches. To overcome this key obstacle hindering effective immunotherapy, we isolated an HLA-A2-restricted T-cell receptor (TCR) with high avidity for human TERT from vaccinated HLA-A*0201 transgenic mice. Using several relevant humanized mouse models, we demonstrate that TCR-transduced T cells were able to control human B-CLL progression in vivo and limited tumor growth in several human, solid transplantable cancers. TERT-based adoptive immunotherapy selectively eliminated tumor cells, failed to trigger a self-MHC-restricted fratricide of T cells, and was associated with toxicity against mature granulocytes, but not toward human hematopoietic progenitors in humanized immune reconstituted mice. These data support the feasibility of TERT-based adoptive immunotherapy in clinical oncology, highlighting, for the first time, the possibility of utilizing a high avidity TCR specific for human TERT. Cancer Res; 76(9); 2540-51. (c)2016 AACR. PMID- 27197264 TI - Stromal-Based Signatures for the Classification of Gastric Cancer. AB - Treatment of metastatic gastric cancer typically involves chemotherapy and monoclonal antibodies targeting HER2 (ERBB2) and VEGFR2 (KDR). However, reliable methods to identify patients who would benefit most from a combination of treatment modalities targeting the tumor stroma, including new immunotherapy approaches, are still lacking. Therefore, we integrated a mouse model of stromal activation and gastric cancer genomic information to identify gene expression signatures that may inform treatment strategies. We generated a mouse model in which VEGF-A is expressed via adenovirus, enabling a stromal response marked by immune infiltration and angiogenesis at the injection site, and identified distinct stromal gene expression signatures. With these data, we designed multiplexed IHC assays that were applied to human primary gastric tumors and classified each tumor to a dominant stromal phenotype representative of the vascular and immune diversity found in gastric cancer. We also refined the stromal gene signatures and explored their relation to the dominant patient phenotypes identified by recent large-scale studies of gastric cancer genomics (The Cancer Genome Atlas and Asian Cancer Research Group), revealing four distinct stromal phenotypes. Collectively, these findings suggest that a genomics based systems approach focused on the tumor stroma can be used to discover putative predictive biomarkers of treatment response, especially to antiangiogenesis agents and immunotherapy, thus offering an opportunity to improve patient stratification. Cancer Res; 76(9); 2573-86. (c)2016 AACR. PMID- 27197265 TI - The Ribonucleic Complex HuR-MALAT1 Represses CD133 Expression and Suppresses Epithelial-Mesenchymal Transition in Breast Cancer. AB - Epithelial-to-mesenchymal transition (EMT) is a core process underlying cell movement during embryonic development and morphogenesis. Cancer cells hijack this developmental program to execute a multi-step cascade, leading to tumorigenesis and metastasis. CD133 (PROM1), a marker of cancer stem cells, has been shown to facilitate EMT in various cancers, but the regulatory networks controlling CD133 gene expression and function in cancer remain incompletely delineated. In this study, we show that a ribonucleoprotein complex including the long noncoding RNA MALAT1 and the RNA-binding protein HuR (ELAVL1) binds the CD133 promoter region to regulate its expression. In luminal nonmetastatic MCF-7 breast cancer cells, HuR silencing was sufficient to upregulate N-cadherin (CDH2) and CD133 along with a migratory and mesenchymal-like phenotype. Furthermore, we found that in the basal-like metastatic cell line MDA-MB-231 and primary triple-negative breast cancer tumor cells, the repressor complex was absent from the CD133-regulatory region, but was present in the MCF-7 and primary ER+ tumor cells. The absence of the complex from basal-like cells was attributed to diminished expression of MALAT1, which, when overexpressed, dampened CD133 levels. In conclusion, our findings suggest that the failure of a repressive complex to form or stabilize in breast cancer promotes CD133 upregulation and an EMT-like program, providing new mechanistic insights underlying the control of prometastatic processes. Cancer Res; 76(9); 2626-36. (c)2016 AACR. PMID- 27197268 TI - Correction: Grapefruit-Derived Nanovectors Use an Activated Leukocyte Trafficking Pathway to Deliver Therapeutic Agents to Inflammatory Tumor Sites. PMID- 27197269 TI - Correction: Radiation-Induced Loss of Salivary Gland Function Is Driven by Cellular Senescence and Prevented by IL6 Modulation. PMID- 27197266 TI - Second-Generation HSP90 Inhibitor Onalespib Blocks mRNA Splicing of Androgen Receptor Variant 7 in Prostate Cancer Cells. AB - Resistance to available hormone therapies in prostate cancer has been associated with alternative splicing of androgen receptor (AR) and specifically, the expression of truncated and constitutively active AR variant 7 (AR-V7). The transcriptional activity of steroid receptors, including AR, is dependent on interactions with the HSP90 chaperone machinery, but it is unclear whether HSP90 modulates the activity or expression of AR variants. Here, we investigated the effects of HSP90 inhibition on AR-V7 in prostate cancer cell lines endogenously expressing this variant. We demonstrate that AR-V7 and full-length AR (AR-FL) were depleted upon inhibition of HSP90. However, the mechanisms underlying AR-V7 depletion differed from those for AR-FL. Whereas HSP90 inhibition destabilized AR FL and induced its proteasomal degradation, AR-V7 protein exhibited higher stability than AR-FL and did not require HSP90 chaperone activity. Instead, HSP90 inhibition resulted in the reduction of AR-V7 mRNA levels but did not affect total AR transcript levels, indicating that HSP90 inhibition disrupted AR-V7 splicing. Bioinformatic analyses of transcriptome-wide RNA sequencing data confirmed that the second-generation HSP90 inhibitor onalespib altered the splicing of at least 557 genes in prostate cancer cells, including AR. These findings indicate that the effects of HSP90 inhibition on mRNA splicing may prove beneficial in prostate cancers expressing AR-V7, supporting further clinical investigation of HSP90 inhibitors in malignancies no longer responsive to androgen deprivation. Cancer Res; 76(9); 2731-42. (c)2016 AACR. PMID- 27197270 TI - Correction: Aberrant Notch Signaling in the Bone Marrow Microenvironment of Acute Lymphoid Leukemia Suppresses Osteoblast-Mediated Support of Hematopoietic Niche Function. PMID- 27197267 TI - The BRCA1-Delta11q Alternative Splice Isoform Bypasses Germline Mutations and Promotes Therapeutic Resistance to PARP Inhibition and Cisplatin. AB - Breast and ovarian cancer patients harboring BRCA1/2 germline mutations have clinically benefitted from therapy with PARP inhibitor (PARPi) or platinum compounds, but acquired resistance limits clinical impact. In this study, we investigated the impact of mutations on BRCA1 isoform expression and therapeutic response. Cancer cell lines and tumors harboring mutations in exon 11 of BRCA1 express a BRCA1-Delta11q splice variant lacking the majority of exon 11. The introduction of frameshift mutations to exon 11 resulted in nonsense-mediated mRNA decay of full-length, but not the BRCA1-Delta11q isoform. CRISPR/Cas9 gene editing as well as overexpression experiments revealed that the BRCA1-Delta11q protein was capable of promoting partial PARPi and cisplatin resistance relative to full-length BRCA1, both in vitro and in vivo Furthermore, spliceosome inhibitors reduced BRCA1-Delta11q levels and sensitized cells carrying exon 11 mutations to PARPi treatment. Taken together, our results provided evidence that cancer cells employ a strategy to remove deleterious germline BRCA1 mutations through alternative mRNA splicing, giving rise to isoforms that retain residual activity and contribute to therapeutic resistance. Cancer Res; 76(9); 2778-90. (c)2016 AACR. PMID- 27197272 TI - Changes in Epidermal Growth Factor Receptor Gene Copy Number during Oral Carcinogenesis. AB - BACKGROUND: Oral squamous cell carcinoma (OSCC) is a global healthcare problem associated with poor clinical outcomes. Early detection is key to improving patient survival. OSCC may be preceded by clinically recognizable lesions, termed oral potentially malignant disorders (OPMD). As histologic assessment of OPMD does not accurately predict their clinical behavior, biomarkers are required to detect cases at risk of malignant transformation. Epidermal growth factor receptor gene copy number (EGFR GCN) is a validated biomarker in lung non-small cell carcinoma. We examined EGFR GCN in OPMD and OSCC to determine its potential as a biomarker in oral carcinogenesis. METHODS: EGFR GCN was examined by in situ hybridization (ISH) in biopsies from 78 patients with OPMD and 92 patients with early-stage (stages I and II) OSCC. EGFR ISH signals were scored by two pathologists and a category assigned by consensus. The data were correlated with patient demographics and clinical outcomes. RESULTS: OPMD with abnormal EGFR GCN were more likely to undergo malignant transformation than diploid cases. EGFR genomic gain was detected in a quarter of early-stage OSCC, but did not correlate with clinical outcomes. CONCLUSION: These data suggest that abnormal EGFR GCN has clinical utility as a biomarker for the detection of OPMD destined to undergo malignant transformation. Prospective studies are required to verify this finding. It remains to be determined if EGFR GCN could be used to select patients for EGFR-targeted therapies. IMPACT: Abnormal EGFR GCN is a potential biomarker for identifying OPMD that are at risk of malignant transformation. Cancer Epidemiol Biomarkers Prev; 25(6); 927-35. (c)2016 AACR. PMID- 27197271 TI - Effects of a Structured Exercise Program on Physical Activity and Fitness in Colon Cancer Survivors: One Year Feasibility Results from the CHALLENGE Trial. AB - BACKGROUND: There is strong interest in testing lifestyle interventions to improve cancer outcomes; however, the optimal methods for achieving behavior change in large-scale pragmatic trials are unknown. Here, we report the 1-year feasibility results for exercise behavior change in the Canadian Cancer Trials Group CO.21 (CHALLENGE) Trial. METHODS: Between 2009 and 2014, 273 high-risk stage II and III colon cancer survivors from 42 centers in Canada and Australia were randomized to a structured exercise program (SEP; n = 136) or health education materials (HEM; n = 137). The primary feasibility outcome in a prespecified interim analysis was a difference between randomized groups of >=5 metabolic equivalent task (MET)-hours/week in self-reported recreational physical activity (PA) after at least 250 participants reached the 1-year follow-up. Secondary outcomes included health-related fitness. RESULTS: The SEP group reported an increase in recreational PA of 15.6 MET-hours/week compared with 5.1 MET-hours/week in the HEM group [mean difference = +10.5; 95% confidence interval (CI) = +3.1-+17.9; P = 0.002]. The SEP group also improved relative to the HEM group in predicted VO2max (P = 0.068), 6-minute walk (P < 0.001), 30-second chair stand (P < 0.001), 8-foot up-and-go (P = 0.004), and sit-and-reach (P = 0.08). CONCLUSIONS: The behavior change intervention in the CHALLENGE Trial produced a substantial increase in self-reported recreational PA that met the feasibility criterion for trial continuation, resulted in objective fitness improvements, and is consistent with the amount of PA associated with improved colon cancer outcomes in observational studies. IMPACT: The CHALLENGE Trial is poised to determine the causal effects of PA on colon cancer outcomes. Cancer Epidemiol Biomarkers Prev; 25(6); 969-77. (c)2016 AACR. PMID- 27197273 TI - Temporal Trends in Colorectal Cancer Screening among Asian Americans. AB - Asian Americans (AA) are less likely to be screened for colorectal cancer compared with non-Hispanic Whites (NHW), with a widening disparity for some AA subgroups in the early 2000s. Whether these patterns have continued in more recent years is unknown. We examined temporal trends in colorectal cancer screening among AA overall compared with NHWs and by AA subgroup (Chinese, Japanese, Korean, Filipino, South Asian, Vietnamese) using data from the 2003, 2005, 2007, and 2009 California Health Interview Surveys. Unadjusted (PR) and adjusted (aPR) prevalence ratios for colorectal cancer screening, accounting for sociodemographic, health care, and acculturation factors, were calculated for respondents ages 50 to 75 years (NHW n = 60,125; AA n = 6,630). Between 2003 and 2009, colorectal cancer screening prevalence increased from 43.3% to 64.6% in AA (P <= 0.001) and from 58.1% to 71.4% in NHW (P <= 0.001). Unadjusted colorectal cancer screening was significantly lower among AA compared with NHW in 2003 [PR = 0.74; 95% confidence interval (CI), 0.68-0.82], 2005 (PR = 0.78; 95% CI, 0.72 0.84), 2007 (PR = 0.91; 95% CI, 0.85-0.96), and 2009 (PR = 0.90; 95% CI, 0.84 0.97), though disparities narrowed over time. After adjustment, there were no significant differences in colorectal cancer screening between the two groups, except in 2003. In subgroup analyses, between 2003 and 2009, colorectal cancer screening significantly increased by 22% in Japanese, 56% in Chinese, 47% in Filipino, and 94% in Koreans. In our study of California residents, colorectal cancer screening disparities between AA and NHW narrowed, but were not eliminated and screening prevalence among AA remains below nationwide goals, including the Healthy People 2020 goal of increasing colorectal cancer screening prevalence to 70.5%. Cancer Epidemiol Biomarkers Prev; 25(6); 995-1000. (c)2016 AACR. PMID- 27197274 TI - Parity and Oral Contraceptive Use in Relation to Ovarian Cancer Risk in Older Women. AB - BACKGROUND: Several studies have suggested that the ovarian cancer risk reductions associated with parity and oral contraceptive use are weaker in postmenopausal than premenopausal women, yet little is known about the persistence of these reductions as women age. This question gains importance with the increasing numbers of older women in the population. METHODS: We addressed the question using data from three large U.S. cohort studies involving 310,290 white women aged 50+ years at recruitment, of whom 1,815 developed subsequent incident invasive epithelial ovarian cancer. We used Cox regression, stratified by cohort, to examine age-related trends in the HRs per full-term pregnancy and per year of oral contraceptive use. RESULTS: The parity-associated risk reductions waned with age (Ptrend < 0.001 in HR with increasing age), particularly among women aged 75 years or more, for whom we observed no association with parity. However, we observed no such attenuation in the oral contraceptive-associated risk reductions (P = 0.79 for trend in HR with increasing age). CONCLUSION: These findings suggest that prior oral contraceptive use is important for ovarian cancer risk assessment among women of all ages, while the benefits of parity wane as women age. IMPACT: This information, if duplicated in other studies, will be useful to preventive counseling and risk prediction, particularly for women at increased ovarian cancer risk due to a personal history of breast cancer or a family history of ovarian cancer. Cancer Epidemiol Biomarkers Prev; 25(7); 1059-63. (c)2016 AACR. PMID- 27197276 TI - The Effect of Exercise Training on Mediators of Inflammation in Breast Cancer Survivors: A Systematic Review with Meta-analysis. AB - Several sources of evidence indicate that exercise during and after breast cancer could positively modulate the tumor microenvironment. This meta-analysis aimed to determine the effects of exercise training on mediators of inflammation in breast cancer survivors. We searched for randomized controlled trials published from January 1990 to March 2014. An inverse variance method of meta-analysis was performed using a random effects model in the presence of statistical heterogeneity. Eight high-quality trials (n = 478) were included. Exercise improved the serum concentrations of IL6 [weighted mean difference (WMD) = -0.55 pg/mL; 95% confidence interval (CI), -1.02 to -0.09], TNFalpha (WMD = -0.64 pg/mL; 95% CI, -1.21 to -0.06), IL8 (MD = -0.49 pg/mL; 95% CI, -0.89 to -0.09), and IL2 (WMD = 1.03 pg/mL; 95% CI, 0.40 to 1.67). No significant differences were found in the serum concentrations of C-reactive protein (WMD = -0.15; 95% CI, 0.56 to 0.25) or IL10 (WMD = 0.41; 95% CI, -0.18 to 1.02). Exercise training positively modulates chronic low-grade inflammation in women with breast cancer, which may impact upon carcinogenic mechanisms and the tumor microenvironment. These findings align with the other positive effects of exercise for breast cancer survivors, reinforcing the appropriateness of exercise prescription in this population. Cancer Epidemiol Biomarkers Prev; 25(7); 1009-17. (c)2016 AACR. PMID- 27197277 TI - Systematic Review and Meta-study Synthesis of Qualitative Studies Evaluating Facilitators and Barriers to Participation in Colorectal Cancer Screening. AB - Screening reduces the incidence, morbidity, and mortality of colorectal cancer, yet participation tends to be low. We undertook a systematic review and meta study synthesis of qualitative studies to identify facilitators and barriers to colorectal cancer screening participation. We searched major bibliographic databases for records published in all languages from inception to February 2015. Included primary studies that elicited views and perceptions towards colorectal cancer screening were appraised for relevance and quality. We used a two-stage synthesis to create an interpretation of colorectal cancer screening decisions grounded in primary studies; a thematic analysis to group themes and systematically compare studies and a meta-synthesis to generate an expanded theory of colorectal cancer screening participation. Ninety-four studies were included. The decision to participate in colorectal cancer screening depended on an individual's awareness of colorectal cancer screening. Awareness affected views of cancer, attitudes towards colorectal cancer screening modalities, and motivation for screening. Factors mediating awareness included public education to address misconceptions, primary care physician efforts to recommend screening, and the influence of friends and family. Specific barriers to participation in populations with lower participation rates included language barriers, logistical challenges to attending screening tests, and cultural beliefs. This study identifies key barriers, facilitators, and mediators to colorectal cancer screening participation. Cancer Epidemiol Biomarkers Prev; 25(6); 907-17. (c)2016 AACR. PMID- 27197275 TI - Serum Estrogens and Estrogen Metabolites and Endometrial Cancer Risk among Postmenopausal Women. AB - BACKGROUND: Although endometrial cancer is clearly influenced by hormonal factors, few epidemiologic studies have investigated the role of endogenous estrogens or especially estrogen metabolites. METHODS: We conducted a nested case control study within the Women's Health Initiative Observational Study (WHI-OS), a cohort of 93,676 postmenopausal women recruited between 1993 and 1998. Using baseline serum samples from women who were non-current hormone users with intact uteri, we measured 15 estrogens/estrogen metabolites via HPLC/MS-MS among 313 incident endometrial cancer cases (271 type I, 42 type II) and 354 matched controls, deriving adjusted ORs and 95% confidence intervals (CI) for overall and subtype-specific endometrial cancer risk. RESULTS: Parent estrogens (estrone and estradiol) were positively related to endometrial cancer risk, with the highest risk observed for unconjugated estradiol (OR 5th vs. 1st quintile = 6.19; 95% CI, 2.95-13.03, Ptrend = 0.0001). Nearly all metabolites were significantly associated with elevated risks, with some attenuation after adjustment for unconjugated estradiol (residual risks of 2- to 3-fold). Body mass index (kg/m(2), BMI) relations were somewhat reduced after adjustment for estrogen levels. The association with unconjugated estradiol was stronger for type I than type II tumors (Phet = 0.01). CONCLUSIONS: Parent estrogens as well as individual metabolites appeared to exert generalized uterotropic activity, particularly for type I tumors. The effects of obesity on risk were only partially explained by estrogens. IMPACT: These findings enhance our understanding of estrogen mechanisms involved in endometrial carcinogenesis but also highlight the need for studying additional markers that may underlie the effects on risk of certain risk factors, for example, obesity. Cancer Epidemiol Biomarkers Prev; 25(7); 1081-9. (c)2016 AACR. PMID- 27197279 TI - Oral Hygiene and Risk of Nasopharyngeal Carcinoma-A Population-Based Case-Control Study in China. AB - BACKGROUND: The association between oral health and risk of nasopharyngeal carcinoma (NPC) is largely unknown. Further understanding could shed light on potential pathogenic mechanisms and preventive measures. METHODS: We conducted a population-based case-control study in southern China between 2010 and 2014. We enrolled 2,528 incident NPC cases, aged 20-74 years, and 2,596 controls, randomly selected from the total population registers, with frequency matching to the 5 year age and sex distribution of the cases by geographic region. We interviewed subjects using a structured questionnaire inquiring about oral health indicators and potential confounding factors. We used unconditional logistic regression to estimate multivariate-adjusted ORs with 95% confidence intervals (CI). RESULTS: A higher number of filled teeth was associated with an elevated risk of NPC. Individuals with 1 to 3 and more than 3 teeth filled versus none had adjusted ORs of 1.25 (95% CI, 1.06-1.49) and 1.55 (95% CI, 1.13-2.12), respectively (Ptrend = 0.002). Conversely, the adjusted OR for those who brushed teeth twice or more per day versus once or less per day was 0.62 (95% CI, 0.55-0.70). We detected a borderline significant positive association with earlier age at first adult tooth loss. CONCLUSION: Our study suggested a positive association between some indicators of poor oral health and risk of NPC. Further studies are needed to confirm whether the findings are causal and, if so, to further explain the underlying mechanisms. IMPACT: Improvement of oral hygiene might contribute to reducing NPC risk. Cancer Epidemiol Biomarkers Prev; 25(8); 1201-7. (c)2016 AACR. PMID- 27197278 TI - Metabolomic Biomarkers of Prostate Cancer: Prediction, Diagnosis, Progression, Prognosis, and Recurrence. AB - Metabolite profiling is being increasing employed in the study of prostate cancer as a means of identifying predictive, diagnostic, and prognostic biomarkers. This review provides a summary and critique of the current literature. Thirty-three human case-control studies of prostate cancer exploring disease prediction, diagnosis, progression, or treatment response were identified. All but one demonstrated the ability of metabolite profiling to distinguish cancer from benign, tumor aggressiveness, cases who recurred, and those who responded well to therapy. In the subset of studies where biomarker discriminatory ability was quantified, high AUCs were reported that would potentially outperform the current gold standards in diagnosis, prognosis, and disease recurrence, including PSA testing. There were substantial similarities between the metabolites and the associated pathways reported as significant by independent studies, and important roles for abnormal cell growth, intensive cell proliferation, and dysregulation of lipid metabolism were highlighted. The weight of the evidence therefore suggests metabolic alterations specific to prostate carcinogenesis and progression that may represent potential metabolic biomarkers. However, replication and validation of the most promising biomarkers is currently lacking and a number of outstanding methodologic issues remain to be addressed to maximize the utility of metabolomics in the study of prostate cancer. Cancer Epidemiol Biomarkers Prev; 25(6); 887-906. (c)2016 AACR. PMID- 27197280 TI - Alcohol Use and Breast Cancer Survival among Participants in the Women's Health Initiative. AB - BACKGROUND: Alcohol increases the risk of breast cancer even at moderate levels of intake. However, the relationship between alcohol consumption and mortality among breast cancer patients is less clear. METHODS: This study included women from the Women's Health Initiative observational study and randomized trial diagnosed with breast cancer (n = 7,835). Cox proportional hazards regression was used to estimate adjusted HRs and 95% confidence intervals (CI) for overall and breast cancer-specific (BCS) mortality associated with drinking alcohol before or after a breast cancer diagnosis. We also assessed whether changes in drinking habits after diagnosis are related to mortality. RESULTS: Women who were consuming alcohol prior to their breast cancer diagnosis had a nonstatistically significant 24% (95% CI, 0.56-1.04) reduced risk of BCS mortality and a 26% (95% CI, 0.61-0.89) reduced risk of all-cause mortality. Some variation was observed by estrogen receptor (ER) status as alcohol consumption was associated with a 49% (95% CI, 0.31-0.83) reduced risk of BCS mortality among ER(-) patients with no change in risk observed among ER(+) patients (HR = 0.97; 95% CI, 0.31-1.54), though the difference between these risks was not statistically significant (P for interaction = 0.39). Postdiagnosis alcohol consumption, and change in consumption patterns after diagnosis, did not appear to be associated with all cause or BCS mortality. CONCLUSION: In this large study, consumption of alcohol before or after breast cancer diagnosis did not increase risks of overall or cause-specific mortality. IMPACT: Coupled with existing evidence, alcohol consumption is unlikely to have a substantial impact on mortality among breast cancer patients. Cancer Epidemiol Biomarkers Prev; 25(8); 1268-73. (c)2016 AACR. PMID- 27197281 TI - Lower Pectoralis Muscle Area Is Associated with a Worse Overall Survival in Non Small Cell Lung Cancer. AB - BACKGROUND: Muscle wasting is a component of the diagnosis of cancer cachexia and has been associated with poor prognosis. However, recommended tools to measure sarcopenia are limited by poor sensitivity or the need to perform additional scans. We hypothesized that pectoralis muscle area (PMA) measured objectively on chest CT scan may be associated with overall survival (OS) in non-small cell lung cancer (NSCLC). METHODS: We evaluated 252 cases from a prospectively enrolling lung cancer cohort. Eligible cases had CT scans performed prior to the initiation of surgery, radiation, or chemotherapy. PMA was measured in a semi-automated fashion while blinded to characteristics of the tumor, lung, and patient outcomes. RESULTS: Men had a significantly greater PMA than women (37.59 vs. 26.19 cm2, P < 0.0001). In univariate analysis, PMA was associated with age and body mass index (BMI). A Cox proportional hazards model was constructed to account for confounders associated with survival. Lower pectoralis area (per cm2) at diagnosis was associated with an increased hazard of death of 2% (HRadj, 0.98; confidence interval, 0.96-0.99; P = 0.044) while adjusting for age, sex, smoking, chronic bronchitis, emphysema, histology, stage, chemotherapy, radiation, surgery, BMI, and ECOG performance status. CONCLUSIONS: Lower PMA measured from chest CT scans obtained at the time of diagnosis of NSCLC is associated with a worse OS. IMPACT: PMA may be a valuable CT biomarker for sarcopenia-associated lung cancer survival. Cancer Epidemiol Biomarkers Prev; 26(1); 38-43. (c)2016 AACR SEE ALL THE ARTICLES IN THIS CEBP FOCUS SECTION, "THE OBESITY PARADOX IN CANCER EVIDENCE AND NEW DIRECTIONS". PMID- 27197282 TI - Association between Body Powder Use and Ovarian Cancer: The African American Cancer Epidemiology Study (AACES). AB - BACKGROUND: Epidemiologic studies indicate increased ovarian cancer risk among women who use genital powder, but this has not been thoroughly investigated in African American (AA) women, a group with a high prevalence of use. We evaluate the relationship between use of genital powder and nongenital powder in invasive epithelial ovarian cancer (EOC). METHODS: Subjects are 584 cases and 745 controls enrolled in the African American Cancer Epidemiology Study (AACES), an ongoing, population-based case-control study of EOC in AA women in 11 geographic locations in the United States. AA controls were frequency matched to cases on residence and age. Logistic regression was used to calculate ORs and 95% confidence intervals (CI) for associations between genital and nongenital powder exposure and EOC risk, controlling for potential confounders. RESULTS: Powder use was common (62.8% of cases and 52.9% of controls). Genital powder was associated with an increased risk of EOC (OR = 1.44; 95% CI, 1.11-1.86) and a dose-response relationship was found for duration of use and number of lifetime applications (P < 0.05). Nongenital use was also associated with EOC risk, particularly among nonserous EOC cases (OR = 2.28; 95% CI, 1.39-3.74). An association between powder use and upper respiratory conditions suggests an enhanced inflammatory response may explain the association between body powder and EOC. CONCLUSIONS: In a study of AA women, body powder use was significantly associated with EOC risk. IMPACT: The results support that body powder is a modifiable risk factor for EOC among AA women. Cancer Epidemiol Biomarkers Prev; 25(10); 1411-7. (c)2016 AACRSee related commentary by Trabert, p. 1369. PMID- 27197283 TI - Dietary Fat Intake During Adolescence and Breast Density Among Young Women. AB - BACKGROUND: Lack of association between fat intake and breast cancer risk in cohort studies might be attributed to the disregard of temporal effects during adolescence when breasts develop and are particularly sensitive to stimuli. We prospectively examined associations between adolescent fat intakes and breast density. METHOD: Among 177 women who participated in the Dietary Intervention Study in Children, dietary intakes at ages 10-18 years were assessed on five occasions by 24-hour recalls and averaged. We calculated geometric mean and 95% confidence intervals for MRI-measured breast density at ages 25-29 years across quartiles of fat intake using linear mixed-effect regression. RESULTS: Comparing women in the extreme quartiles of adolescent fat intakes, percent dense breast volume (%DBV) was positively associated with saturated fat (mean = 16.4% vs. 21.5%; Ptrend < 0.001). Conversely, %DBV was inversely associated with monounsaturated fat (25.0% vs. 15.8%; Ptrend < 0.001) and the ratio of polyunsaturated fat to saturated fat (P/S ratio; 19.1% vs. 14.3%; Ptrend < 0.001). When examining intake by pubertal stages, %DBV was inversely associated with intake of polyunsaturated fat (20.8% vs. 16.4%; Ptrend = 0.04), long-chain omega-3 fat (17.8% vs. 15.8%; Ptrend < 0.001), and P/S ratio (22.5% vs. 16.1%; Ptrend < 0.001) before menarche, but not after. These associations observed with %DBV were consistently observed with absolute dense breast volume but not with absolute nondense breast volume. CONCLUSIONS: In our study, adolescent intakes of higher saturated fat and lower mono- and polyunsaturated fat are associated with higher breast density measured approximately 15 years later. IMPACT: The fat subtype composition in adolescent diet may be important in early breast cancer prevention. Cancer Epidemiol Biomarkers Prev; 25(6); 918-26. (c)2016 AACR. PMID- 27197284 TI - Association of Common Susceptibility Variants of Pancreatic Cancer in Higher-Risk Patients: A PACGENE Study. AB - Individuals from pancreatic cancer families are at increased risk, not only of pancreatic cancer, but also of melanoma, breast, ovarian, and colon cancers. While some of the increased risk may be due to mutations in high-penetrance genes (i.e., BRCA2, PALB2, ATM, p16/CDKN2A or DNA mismatch repair genes), common genetic variants may also be involved. In a high-risk population of cases with either a family history of pancreatic cancer or early-onset pancreatic cancer (diagnosis before the age of 50 years), we examined the role of genetic variants previously associated with risk of pancreatic, breast, ovarian, or prostate cancer. We genotyped 985 cases (79 early-onset cases, 906 cases with a family history of pancreatic cancer) and 877 controls for 215,389 SNPs using the iSelect Collaborative Oncological Gene-Environment Study (iCOGS) array with custom content. Logistic regression was performed using a log-linear additive model. We replicated several previously reported pancreatic cancer susceptibility loci, including recently identified variants on 2p13.3 and 7p13 (2p13.3, rs1486134: OR = 1.36; 95% CI, 1.13-1.63; P = 9.29 * 10(-4); 7p13, rs17688601: OR = 0.76; 95% CI, 0.63-0.93; P = 6.59 * 10(-3)). For the replicated loci, the magnitude of association observed in these high-risk patients was similar to that observed in studies of unselected patients. In addition to the established pancreatic cancer loci, we also found suggestive evidence of association (P < 5 * 10(-5)) to pancreatic cancer for SNPs at HDAC9 (7p21.1) and COL6A2 (21q22.3). Even in high risk populations, common variants influence pancreatic cancer susceptibility. Cancer Epidemiol Biomarkers Prev; 25(7); 1185-91. (c)2016 AACR. PMID- 27197286 TI - Inflammatory-Related Genetic Variants in Non-Muscle-Invasive Bladder Cancer Prognosis: A Multimarker Bayesian Assessment. AB - BACKGROUND: Increasing evidence points to the role of tumor immunologic environment on urothelial bladder cancer prognosis. This effect might be partly dependent on the host genetic context. We evaluated the association of SNPs in inflammation-related genes with non-muscle-invasive bladder cancer (NMIBC) risk of-recurrence and risk-of-progression. METHODS: We considered 822 NMIBC included in the SBC/EPICURO Study followed-up >10 years. We selected 1,679 SNPs belonging to 251 inflammatory genes. The association of SNPs with risk-of-recurrence and risk-of-progression was assessed using Cox regression single-marker (SMM) and multimarker methods (MMM) Bayes A and Bayesian LASSO. Discriminative abilities of the models were calculated using the c index and validated with bootstrap cross validation procedures. RESULTS: While no SNP was found to be associated with risk of-recurrence using SMM, three SNPs in TNIP1, CD5, and JAK3 showed very strong association with posterior probabilities >90% using MMM. Regarding risk-of progression, one SNP in CD3G was significantly associated using SMM (HR, 2.69; P = 1.55 * 10(-5)) and two SNPs in MASP1 and AIRE, showed a posterior probability >=80% with MMM. Validated discriminative abilities of the models without and with the SNPs were 58.4% versus 60.5% and 72.1% versus 72.8% for risk-of-recurrence and risk-of-progression, respectively. CONCLUSIONS: Using innovative analytic approaches, we demonstrated that SNPs in inflammatory-related genes were associated with NMIBC prognosis and that they improve the discriminative ability of prognostic clinical models for NMIBC. IMPACT: This study provides proof of concept for the joint effect of genetic variants in improving the discriminative ability of clinical prognostic models. The approach may be extended to other diseases. Cancer Epidemiol Biomarkers Prev; 25(7); 1144-50. (c)2016 AACR. PMID- 27197285 TI - Chronic Recreational Physical Inactivity and Epithelial Ovarian Cancer Risk: Evidence from the Ovarian Cancer Association Consortium. AB - BACKGROUND: Despite a large body of literature evaluating the association between recreational physical activity and epithelial ovarian cancer (EOC) risk, the extant evidence is inconclusive, and little is known about the independent association between recreational physical inactivity and EOC risk. We conducted a pooled analysis of nine studies from the Ovarian Cancer Association Consortium to investigate the association between chronic recreational physical inactivity and EOC risk. METHODS: In accordance with the 2008 Physical Activity Guidelines for Americans, women reporting no regular, weekly recreational physical activity were classified as inactive. Multivariable logistic regression was utilized to estimate the ORs and 95% confidence intervals (CI) for the association between inactivity and EOC risk overall and by subgroups based upon histotype, menopausal status, race, and body mass index. RESULTS: The current analysis included data from 8,309 EOC patients and 12,612 controls. We observed a significant positive association between inactivity and EOC risk (OR = 1.34; 95% CI, 1.14-1.57), and similar associations were observed for each histotype. CONCLUSIONS: In this large pooled analysis examining the association between recreational physical inactivity and EOC risk, we observed consistent evidence of an association between chronic inactivity and all EOC histotypes. IMPACT: These data add to the growing body of evidence suggesting that inactivity is an independent risk factor for cancer. If the apparent association between inactivity and EOC risk is substantiated, additional work via targeted interventions should be pursued to characterize the dose of activity required to mitigate the risk of this highly fatal disease. Cancer Epidemiol Biomarkers Prev; 25(7); 1114-24. (c)2016 AACR. PMID- 27197288 TI - A Randomized Controlled Trial of Progressively Reduced Nicotine Content Cigarettes on Smoking Behaviors, Biomarkers of Exposure, and Subjective Ratings. AB - BACKGROUND: The U.S. FDA has the authority to reduce cigarette nicotine content if found to benefit public health. Reduced nicotine content (RNC) cigarette use does not appear to increase harm exposure, but studies have not rigorously assessed smoking behavior or used a comprehensive panel of biomarkers. This study examined the effects of progressively decreasing RNC cigarettes on smoking behaviors, biomarkers of exposure, and subjective ratings. METHODS: One hundred and fifty-eight daily, non-treatment-seeking smokers participated in a 35-day randomized, unblinded, parallel study. After a 5-day baseline period, participants were randomly assigned to an experimental group (n = 80) that smoked progressively decreasing RNC cigarettes during three 10-day periods, or control group (n = 78) that smoked their own brand throughout the study. RESULTS: Daily cigarette consumption significantly increased for the intermediate RNCs (P's < 0.001) but approached baseline rate for the lowest RNC (P = 0.686); in contrast, puffing behavior significantly decreased at intermediate levels and increased for the lowest RNC (P's < 0.001). Cotinine and NNAL significantly decreased by RNC period (P's <= 0.001-0.02), whereas CO boost initially increased (P's = 0.001 0.005). 1-HOP did not change by period (P = 0.109). CONCLUSIONS: Smoking behaviors changed by RNC period via CPD and puffing behavior. Biomarkers of exposure generally decreased with nicotine content. IMPACT: Findings suggest that RNC use does not ubiquitously reduce smoking behaviors or biomarkers, yet the lowest RNC level tested may reduce harm exposure. This emphasizes the importance of using multiple behavioral and biologic measures to address the impact of RNC cigarette smoking. Cancer Epidemiol Biomarkers Prev; 25(7); 1125-33. (c)2016 AACR. PMID- 27197289 TI - A Composite Cytology-Histology Endpoint Allows a More Accurate Estimate of Anal High-Grade Squamous Intraepithelial Lesion Prevalence. AB - BACKGROUND: There is debate about the accuracy of anal cytology and high resolution anoscopy (HRA), in the diagnosis of anal human papillomavirus (HPV) related squamous intraepithelial lesions (SIL). Few studies have performed both simultaneously in a large sample of high-risk individuals. METHODS: At baseline in a community-based cohort of HIV-infected and uninfected homosexual men ages >=35 years in Sydney, Australia, all men underwent anal swabbing for cytology and HPV genotyping, and HRA-guided biopsy. We evaluated the separate and combined diagnostic accuracy of cytology and histology, based on a comparison with the prevalence of HPV16 and other high-risk (HR) HPV. We examined trends in HPV prevalence across cytology-histology combinations. RESULTS: Anal swab, HRA, and HPV genotyping results were available for 605 of 617 participants. The prevalence of cytologically predicted high-grade SIL (HSIL, 17.9%) was lower than histologically diagnosed HSIL (31.7%, P < 0.001). The prevalence of composite HSIL (detected by either method) was 37.7%. HPV16 prevalence was similar in men with HSIL by cytology (59.3%), HSIL by histology (51.0%), and composite-HSIL (50.0%). HPV16 prevalence was 31.1% in men with composite-atypical squamous cells suggestive of HSIL, to 18.5% in men with composite-low-grade SIL, to 12.1% in men with composite-negative results (Ptrend < 0.001). CONCLUSIONS: Significantly more HSIL was detected when a composite cytology-histology endpoint was used. Increasing grade of composite endpoint was associated with increasing HPV16 prevalence. IMPACT: These data suggest that a composite cytology-histology endpoint reflects meaningful disease categories and is likely to be an important biomarker in anal cancer prevention. Cancer Epidemiol Biomarkers Prev; 25(7); 1134-43. (c)2016 AACR. PMID- 27197287 TI - Selenium- or Vitamin E-Related Gene Variants, Interaction with Supplementation, and Risk of High-Grade Prostate Cancer in SELECT. AB - BACKGROUND: Epidemiologic studies and secondary analyses of randomized trials supported the hypothesis that selenium and vitamin E lower prostate cancer risk. However, the Selenium and Vitamin E Cancer Prevention Trial (SELECT) showed no benefit of either supplement. Genetic variants involved in selenium or vitamin E metabolism or transport may underlie the complex associations of selenium and vitamin E. METHODS: We undertook a case-cohort study of SELECT participants randomized to placebo, selenium, or vitamin E. The subcohort included 1,434 men; our primary outcome was high-grade prostate cancer (N = 278 cases, Gleason 7 or higher cancer). We used weighted Cox regression to examine the association between SNPs and high-grade prostate cancer risk. To assess effect modification, we created interaction terms between randomization arm and genotype and calculated log likelihood statistics. RESULTS: We noted statistically significant (P < 0.05) interactions between selenium assignment, SNPs in CAT, SOD2, PRDX6, SOD3, and TXNRD2, and high-grade prostate cancer risk. Statistically significant SNPs that modified the association of vitamin E assignment and high-grade prostate cancer included SEC14L2, SOD1, and TTPA In the placebo arm, several SNPs, hypothesized to interact with supplement assignment and risk of high-grade prostate cancer, were also directly associated with outcome. CONCLUSION: Variants in selenium and vitamin E metabolism/transport genes may influence risk of overall and high-grade prostate cancer, and may modify an individual man's response to vitamin E or selenium supplementation with regards to these risks. IMPACT: The effect of selenium or vitamin E supplementation on high-grade prostate cancer risk may vary by genotype. Cancer Epidemiol Biomarkers Prev; 25(7); 1050-8. (c)2016 AACR. PMID- 27197291 TI - Genetic Variation Associated with Longer Telomere Length Increases Risk of Chronic Lymphocytic Leukemia. AB - BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world. Shorter mean telomere length in leukemic cells has been associated with more aggressive disease. Germline polymorphisms in telomere maintenance genes affect telomere length and may contribute to CLL susceptibility. METHODS: We collected genome-wide data from two groups of patients with CLL (N = 273) and two control populations (N = 5,725). In ancestry-adjusted case-control comparisons, we analyzed eight SNPs in genes definitively associated with inter individual variation in leukocyte telomere length (LTL) in prior genome-wide association studies: ACYP2, TERC, NAF1, TERT, OBFC1, CTC1, ZNF208, and RTEL1 RESULTS: Three of the eight LTL-associated SNPs were associated with CLL risk at P < 0.05, including those near: TERC [OR, 1.46; 95% confidence interval (CI), 1.15-1.86; P = 1.8 * 10(-3)], TERT (OR = 1.23; 95% CI, 1.02-1.48; P = 0.030), and OBFC1 (OR, 1.36; 95% CI, 1.08-1.71; P = 9.6 * 10(-3)). Using a weighted linear combination of the eight LTL-associated SNPs, we observed that CLL patients were predisposed to longer LTL than controls in both case-control sets (P = 9.4 * 10( 4) and 0.032, respectively). CLL risk increased monotonically with increasing quintiles of the weighted linear combination. CONCLUSIONS: Genetic variants in TERC, TERT, and OBFC1 are associated with both longer LTL and increased CLL risk. Because the human CST complex competes with shelterin for telomeric DNA, future work should explore the role of OBFC1 and other CST complex genes in leukemogenesis. IMPACT: A genetic predisposition to longer telomere length is associated with an increased risk of CLL, suggesting that the role of telomere length in CLL etiology may be distinct from its role in disease progression. Cancer Epidemiol Biomarkers Prev; 25(7); 1043-9. (c)2016 AACR. PMID- 27197290 TI - A Tissue Systems Pathology Assay for High-Risk Barrett's Esophagus. AB - BACKGROUND: Better methods are needed to predict risk of progression for Barrett's esophagus. We aimed to determine whether a tissue systems pathology approach could predict progression in patients with nondysplastic Barrett's esophagus, indefinite for dysplasia, or low-grade dysplasia. METHODS: We performed a nested case-control study to develop and validate a test that predicts progression of Barrett's esophagus to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC), based upon quantification of epithelial and stromal variables in baseline biopsies. Data were collected from Barrett's esophagus patients at four institutions. Patients who progressed to HGD or EAC in >=1 year (n = 79) were matched with patients who did not progress (n = 287). Biopsies were assigned randomly to training or validation sets. Immunofluorescence analyses were performed for 14 biomarkers and quantitative biomarker and morphometric features were analyzed. Prognostic features were selected in the training set and combined into classifiers. The top-performing classifier was assessed in the validation set. RESULTS: A 3-tier, 15-feature classifier was selected in the training set and tested in the validation set. The classifier stratified patients into low-, intermediate-, and high-risk classes [HR, 9.42; 95% confidence interval, 4.6-19.24 (high-risk vs. low-risk); P < 0.0001]. It also provided independent prognostic information that outperformed predictions based on pathology analysis, segment length, age, sex, or p53 overexpression. CONCLUSION: We developed a tissue systems pathology test that better predicts risk of progression in Barrett's esophagus than clinicopathologic variables. IMPACT: The test has the potential to improve upon histologic analysis as an objective method to risk stratify Barrett's esophagus patients. Cancer Epidemiol Biomarkers Prev; 25(6); 958-68. (c)2016 AACR. PMID- 27197292 TI - PIWI-Interacting RNAs in Gliomagenesis: Evidence from Post-GWAS and Functional Analyses. AB - BACKGROUND: PIWI-interacting RNAs (piRNAs), the largest class of noncoding RNAs in mammals, cooperate with PIWI proteins to safeguard the genome from insertional mutations during germline development. Although a growing number of studies have linked the PIWI-piRNA pathway to carcinogenesis, the role of piRNAs in glioma has not been explored. METHODS: Utilizing directly measured and imputed genotypes from the GliomaScan genome-wide association study (1,840 cases and 2,401 controls), genetic variants in 1,428 piRNAs were analyzed for association with glioma risk. In vitro assays were performed to interrogate the functional impact of a top identified piRNA and its variant allele. RESULTS: Variants in five piRNAs were considered to be associations of interest and four of these showed narrow clusters of enhanced association signals surrounding the index variant. Functional analyses of one of these piRNAs, piR-598, revealed that transfection of the wild-type piRNA impacted expression of genes involved in cell death/survival and reduced glioma cell viability and colony formation. However, upon delivery of piR-598 containing the variant allele at rs147061479 [OR, 1.80; 95% confidence interval (CI), 1.33-2.46; P = 1.69 * 10(-4)], cell proliferation was sharply increased. CONCLUSIONS: The genetic association analysis identifies several piRNAs associated with glioma risk, and follow-up functional analyses suggest that variant rs147061479 in piR-598 increases glioma risk by abolishing the tumor-suppressive function of piR-598, instead conferring growth-promoting properties. IMPACT: This transdisciplinary study demonstrates a role of piRNAs in gliomagenesis by evidence from both post-GWAS and in vitro functional analyses and supports expanded investigation into the link between the PIWI-piRNA pathway and cancer. Cancer Epidemiol Biomarkers Prev; 25(7); 1073-80. (c)2016 AACR. PMID- 27197294 TI - Clinicopathologic Features of Colorectal Carcinoma in HIV-Positive Patients. AB - BACKGROUND: Emerging evidence suggests differences in colorectal cancer in HIV infected patients (HIV(+)) compared with HIV(-) patients. Microsatellite instability (MSI), occurring in a subset of colorectal cancer, is present at a higher rate in certain cancers in HIV(+) patients. Colorectal cancer with MSI share some characteristics with those reported for HIV(+) colorectal cancer. On this premise, we studied clinical and pathologic features of HIV(+) colorectal cancer and evaluated for MSI using matched HIV(-) colorectal cancer controls. METHODS: Two nested, matched cohorts were identified from a hospital-based cohort of colorectal cancer patients. HIV(+) colorectal cancers were identified and random control patients were matched for selected characteristics. Mismatch repair protein (MMR) IHC was performed as the detection method for MSI. Variables were compared between cases and controls using fixed-effects logit modeling to account for matching. RESULTS: We included 184 colorectal cancer samples (38 HIV(+), 146 HIV(-) control). Median patient age at colorectal cancer onset was 55. When compared with HIV(-) colorectal cancer, HIV(+) patients were more likely to have smoked (P = 0.001), have right-sided colorectal cancer (37% vs. 14%; P = 0.003), and tumor-infiltrating lymphocytes (TIL) above 50/10 high-power fields (21% vs. 7%). There was no difference in MMR protein expression (P = 0.6). HIV(+) colorectal cancer patients had reduced overall survival (P = 0.02) but no difference in progression-free survival. CONCLUSIONS: HIV(+) patients developed colorectal cancer at a lower median age than population estimates, had a higher frequency of right-sided disease, and increased TILs, suggesting potential biologic differences compared with uninfected patients. IMPACT: Clinicopathologic differences in colorectal cancer of HIV(+) persons may have implications for tumor pathogenesis. Cancer Epidemiol Biomarkers Prev; 25(7); 1098-104. (c)2016 AACR. PMID- 27197293 TI - Exercise-Induced Dose-Response Alterations in Adiponectin and Leptin Levels Are Dependent on Body Fat Changes in Women at Risk for Breast Cancer. AB - BACKGROUND: Dysregulation of adipokines, such as adiponectin and leptin, is associated with a variety of chronic diseases, including cancer. Physical activity protects against breast cancer and one of the mechanisms which may underlie this association is exercise-induced changes in adipokine levels. The WISER Sister Trial was a three-armed randomized controlled trial in premenopausal women (n = 137) with an elevated risk for breast cancer. METHODS: A 5-menstrual cycle-long dosed aerobic exercise intervention compared low-dose exercise (150 min/wk; n = 44) or high-dose exercise (300 min/wk; n = 48) with a control group asked to maintain usual activity levels (n = 45). Exercise intensity progressed to and was maintained at 70% to 80% of age predicted heart rate max. Body composition and adipokine levels were measured at baseline and follow-up. RESULTS: We observed significant linear trends for increased fitness capacity (Delta%: -2.0% control, 10.1% low dose, 13.1% high dose), decreased fat tissue-to total tissue mass (Delta%: 0.7% control, -2.9% low dose, -3.7% high dose), increased body fat adjusted adiponectin (Delta%: -0.6% control, 0.6% low dose, 0.9% high dose), and decreased body fat adjusted leptin (Delta%: 0.7% control, 8.2% low dose, -10.2% high dose). CONCLUSIONS: In this randomized clinical trial of premenopausal women at risk for breast cancer, we demonstrate a dose-response effect of exercise on adiponectin and leptin and that dose response is dependent on changes in body fat. IMPACT: Improved adipokine levels, achieved by aerobic exercise training-induced decreases in body fat, may decrease breast cancer risk for high-risk premenopausal women. Cancer Epidemiol Biomarkers Prev; 25(8); 1195 200. (c)2016 AACR. PMID- 27197295 TI - Elevated Expression of Human Papillomavirus-16/18 E6 Oncoprotein Associates with Persistence of Viral Infection: A 3-Year Prospective Study in China. AB - BACKGROUND: An association between high-risk human papillomavirus (HR-HPV) oncoprotein expression and viral persistence has been suggested by the outcome of etiology studies, but there are no epidemiologic studies evaluating that link. METHODS: We performed a 3-year prospective study in which 2,498 Chinese women ages 25 to 65 years were screened by six screening tests, including the Onco E6: Cervical Test (Arbor Vita Corporation) in 2011 (baseline). Six-hundred and ninety women who were positive for any of the tests and a random sample of 164 women with all negative results received colposcopy, and cervical specimens for the cobas 4800 HPV test ("cobas," Roche Molecular Systems) were collected before colposcopy; of this group, 737 cervical specimens were collected to perform cobas and Onco E6: Cervical Test in 2014 (follow-up). Twenty-four cases of HPV16/18 E6 positives and 204 selected controls at baseline, 13 cases of HPV16/18 E6 positive and another 204 selected controls at follow-up were analyzed separately using unconditional logistical regression models to estimate ORs and 95% confidence intervals (CI). RESULTS: Compared with women who were HPV16 E6 oncoprotein negative at baseline, women in the E6-positive group had a much higher risk of HPV persistence (adjusted OR, 54.64; 95% CI, 7.19-415.09) at 3-year follow-up; a statistically strong association was also found between HPV16/18 HPV persistence and E6 oncoprotein expression detected at follow-up (adjusted OR, 360.57; 95% CI, 28.30-4,593.55). CONCLUSIONS: A single detection of HPV16/18 E6 oncoprotein expression was strongly associated with viral persistence. IMPACT: HPV16/18 E6 oncoprotein constitutes a marker for risk of HPV persistence. Cancer Epidemiol Biomarkers Prev; 25(7); 1167-74. (c)2016 AACR. PMID- 27197296 TI - Comprehensive Evaluation of Medical Conditions Associated with Risk of Non Hodgkin Lymphoma using Medicare Claims ("MedWAS"). AB - BACKGROUND: Certain medical conditions affect risk of non-Hodgkin lymphoma (NHL), but the full range of associations is unknown. We implemented a novel method ("medical condition-wide association study," MedWAS) to comprehensively evaluate medical risk factors for NHL documented in administrative health claims. METHODS: Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we conducted a case-control study comparing NHL cases [N = 52,691, age 66+ years, with five subtypes: chronic lymphocytic leukemia/small lymphocytic lymphoma, diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, marginal zone lymphoma (MZL), T-cell lymphoma (TCL)] to controls (N = 200,000). We systematically screened for associations with 5,926 medical conditions documented in Medicare claims more than 1 year before selection. RESULTS: Fifty-five conditions were variously associated with NHL. Examples include well-established associations of human immunodeficiency virus, solid organ transplantation, and hepatitis C virus with increased DLBCL risk (ORs 3.83, 4.27, and 1.74, respectively), and autoimmune conditions with DLBCL and MZL (e.g., ORs of 2.10 and 4.74, respectively, for Sjogren syndrome). Risks for all NHL subtypes were increased after diagnoses of nonmelanoma skin cancer (ORs 1.19-1.55), actinic keratosis (1.12-1.25), or hemolytic anemia (1.64-4.07). Nine additional skin conditions increased only TCL risk (ORs 2.20-4.12). Diabetes mellitus was associated with increased DLBCL risk (OR 1.09). Associations varied significantly across NHL subtypes for 49 conditions (89%). CONCLUSION: Using an exploratory method, we found numerous medical conditions associated with NHL risk, and many associations varied across NHL subtypes. IMPACT: These results point to etiologic heterogeneity among NHL subtypes. MedWAS is a new method for assessing the etiology of cancer and other diseases. Cancer Epidemiol Biomarkers Prev; 25(7); 1105-13. (c)2016 AACR. PMID- 27197297 TI - The Effect of Patient and Contextual Characteristics on Racial/Ethnic Disparity in Breast Cancer Mortality. AB - BACKGROUND: Racial/ethnic disparity in breast cancer-specific mortality in the United States is well documented. We examined whether accounting for racial/ethnic differences in the prevalence of clinical, patient, and lifestyle and contextual factors that are associated with breast cancer-specific mortality can explain this disparity. METHODS: The California Breast Cancer Survivorship Consortium combined interview data from six California-based breast cancer studies with cancer registry data to create a large, racially diverse cohort of women with primary invasive breast cancer. We examined the contribution of variables in a previously reported Cox regression baseline model plus additional contextual, physical activity, body size, and comorbidity variables to the racial/ethnic disparity in breast cancer-specific mortality. RESULTS: The cohort comprised 12,098 women. Fifty-four percent were non-Latina Whites, 17% African Americans, 17% Latinas, and 12% Asian Americans. In a model adjusting only for age and study, breast cancer-specific HRs relative to Whites were 1.69 (95% CI, 1.46-1.96), 1.00 (0.84-1.19), and 0.52 (0.33-0.85) for African Americans, Latinas, and Asian Americans, respectively. Adjusting for baseline-model variables decreased disparity primarily by reducing the HR for African Americans to 1.13 (0.96-1.33). The most influential variables were related to disease characteristics, neighborhood socioeconomic status, and smoking status at diagnosis. Other variables had negligible impact on disparity. CONCLUSIONS: Although contextual, physical activity, body size, and comorbidity variables may influence breast cancer-specific mortality, they do not explain racial/ethnic mortality disparity. IMPACT: Other factors besides those investigated here may explain the existing racial/ethnic disparity in mortality. Cancer Epidemiol Biomarkers Prev; 25(7); 1064-72. (c)2016 AACR. PMID- 27197298 TI - Association between Glucuronidation Genotypes and Urinary NNAL Metabolic Phenotypes in Smokers. AB - BACKGROUND: The most abundant and potent carcinogenic tobacco-specific nitrosamine in tobacco and tobacco smoke is 4-(methylnitrosamino)-1-(3-pyridyl)-1 butanone (NNK). In vivo, NNK is rapidly metabolized to both the (R)- and (S) enantiomers of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), which possesses similar carcinogenic properties as NNK. The major detoxification pathway for both NNAL enantiomers is glucuronidation by UDP glucuronosyltransferase (UGT) enzymes including UGT2B10 and UGT2B17. The goal of the present study was to directly examine the role of UGT genotypes on urinary levels of NNAL glucuronides in smokers. METHODS: NNAL-N-Gluc, (R)-NNAL-O-Gluc, (S)-NNAL-O-Gluc, and free NNAL were simultaneously and directly quantified in the urine of smokers by LC/MS analysis. Genotypes were determined by TaqMan assay using genomic DNA. RESULTS: The functional knockout polymorphism in the UGT2B10 gene at codon 67 (Asp>Tyr) was significantly (P < 0.0001) associated with a 93% decrease in creatinine-adjusted NNAL-N-Gluc. The polymorphic whole-gene deletion of the UGT2B17 gene was associated with significant (P = 0.0048) decreases in the levels of creatinine-adjusted (R)-NNAL-O-Gluc, with a 32% decrease in the levels of urinary (R)-NNAL-O-Gluc/(S)-NNAL-O-Gluc among subjects with the UGT2B17 (*2/*2) genotype as compared to subjects with the UGT2B17 (*1/*1) genotype. CONCLUSIONS: These results suggest that functional polymorphisms in UGT2B10 and UGT2B17 are associated with a reduced detoxification capacity against NNAL and may therefore affect individual cancer risk upon exposure to tobacco. IMPACT: This is the first report to clearly demonstrate strong genotype-phenotype associations between both the UGT2B10 codon 67 Asp=200 nucleotides) compared with miRNAs. In blood, long RNAs may be protected by serum extracellular vesicles, such as apoptotic bodies (AB), microvesicles (MV), and exosomes (EXO). They are potential biomarkers for identifying cancer. METHODS: Sera from 76 preoperative colorectal cancer patients, 76 age- and sex-matched healthy subjects, and 20 colorectal adenoma patients without colorectal cancer were collected. We investigated the distribution of long RNAs into the three vesicles. Seventy-nine cancer-related long RNAs were chosen and detected using qPCR. RESULTS: The quantity of long RNA has varying distribution among three subtypes of extracellular vesicles in serum. Most mRNA and lncRNA genes had higher quantity in EXOs than that in ABs and MVs, whereas MVs contain lowest quantity. We investigated 79 long RNAs chosen from The Cancer Genome Atlas and the LncRNADisease database in the sera of healthy patients, and those with colorectal cancer. In the training and test sets, the AUCs were 0.936 and 0.877, respectively. The AUC of total serum RNA was lower (0.857) than that of exosomal RNA in the same samples (0.936). CONCLUSION: The present study shows that exosomal mRNAs and lncRNAs in serum could be used as biomarkers to detect colorectal cancer. IMPACT: Among three types of vesicles in sera, EXOs were the richest reservoir for almost all measured long RNAs. The combination of two mRNAs, KRTAP5-4 and MAGEA3, and one lncRNA, BCAR4, could be potential candidates to detect colorectal cancer. Cancer Epidemiol Biomarkers Prev; 25(7); 1158-66. (c)2016 AACR. PMID- 27197302 TI - Work Loss Duration and Predictors Following Rectal Cancer Treatment among Patients with and without Prediagnostic Work Loss. AB - BACKGROUND: The number of working-age rectal cancer survivors is increasing due to early detection and improved treatment. However, work loss duration and predictors among them have not been studied thoroughly. METHODS: We identified 3,438 patients with stage I-III rectal cancer, 18 to 61 years of age in the Swedish Colorectal Cancer Register 1996-2009. Information on work loss due to sick leave or disability pension was collected from 2 years before diagnosis to 5 years after (until December 31st, 2013). Incidence rate ratios (IRR) of work loss were estimated in a negative binominal model by clinical characteristics for the 1st and 2nd-5th years after diagnosis. Patients were stratified by prediagnostic work loss. RESULTS: Patients without prediagnostic work loss (74%) experienced median 147 days (25th and 75th percentile: 55 and 281) of work loss during the 1st year after diagnosis. Work loss rates (2nd-5th years) were significantly increased among relapse-free patients diagnosed in stage III [IRR = 1.92; 95% confidence interval (CI), 1.52-2.43], operated with abdominoperineal resection (IRR = 1.26; 95% CI, 1.03-1.56), and treated with neoadjuvant (chemo)radiotherapy (IRR = 1.46; 95% CI, 1.06-2.02). Patients with prediagnostic work loss (26%) experienced median 336 days (25th and 75th percentile: 183 and 365) of work loss during the 1st year, and rates did not vary clinically till 5 years. CONCLUSION: Without prediagnostic work loss, disease- and treatment-related factors could help identify rectal cancer patients in need of early interventions to facilitate return to work. IMPACT: Clinical awareness around prediagnostic and postdiagnostic work loss and individualized cancer rehabilitation programs should be emphasized among cancer survivors. Cancer Epidemiol Biomarkers Prev; 25(6); 987-94. (c)2016 AACR. PMID- 27197303 TI - Trastuzumab, but Not Pertuzumab, Dysregulates HER2 Signaling to Mediate Inhibition of Autophagy and Increase in Reactive Oxygen Species Production in Human Cardiomyocytes. AB - Dysregulation of autophagy has been implicated in various cardiovascular diseases. Trastuzumab, a humanized monoclonal antibody, binds to HER2 domain IV and is approved for the treatment of HER2-positive breast cancer. Trastuzumab therapy is associated with considerable cardiotoxicity, the mechanism of which remains unclear. HER2 signaling plays a pivotal role in cardiomyocyte development and survival and is essential for the prevention of cardiomyopathy. However, a direct link has not been confirmed between trastuzumab-induced cardiomyopathy and impaired HER2 signaling. Our data reveal a novel mechanism by which trastuzumab dysregulates HER2 signaling and impairs basal autophagic process in human primary cardiomyocytes. Specifically, trastuzumab treatment leads to the phosphorylation of HER1-Y845 and HER2-Y1248 and the activation of Erk. This in turn results in upregulation of mTOR signaling pathway and subsequently inhibition of autophagy in primary cardiomyocytes and C57BL/6 mice. Trastuzumab-induced downregulation of autophagy is further supported by the fact that trastuzumab treatment reduces protein levels of autophagosome-associated signaling molecules such as Atg 5-12, Atg 7, Atg 14, and Beclin 1. We further demonstrated that trastuzumab-mediated inhibition of autophagy resulted in the increased production of reactive oxygen species (ROS) in cardiomyocytes. Pertuzumab, another anti-HER2 therapeutic mAb binding to HER2 domain II, fails to modulate HER2 signaling and is unable to inhibit autophagy and to increase ROS production in cardiomyocytes. This study provides novel mechanistic insights into trastuzumab-induced cardiotoxicity, which may assist in formulating novel approaches for clinical management of trastuzumab-induced cardiomyopathy. Mol Cancer Ther; 15(6); 1321-31. (c)2016 AACR. PMID- 27197304 TI - Triptolide Induces Cell Killing in Multidrug-Resistant Tumor Cells via CDK7/RPB1 Rather than XPB or p44. AB - Multidrug resistance (MDR) is a major cause of tumor treatment failure; therefore, drugs that can avoid this outcome are urgently needed. We studied triptolide, which directly kills MDR tumor cells with a high potency and a broad spectrum of cell death. Triptolide did not inhibit P-glycoprotein (P-gp) drug efflux and reduced P-gp and MDR1 mRNA resulting from transcription inhibition. Transcription factors including c-MYC, SOX-2, OCT-4, and NANOG were not correlated with triptolide-induced cell killing, but RPB1, the largest subunit of RNA polymerase II, was critical in mediating triptolide's inhibition of MDR cells. Triptolide elicited antitumor and anti-MDR activity through a universal mechanism: by activating CDK7 by phosphorylating Thr170 in both parental and MDR cell lines and in SK-OV-3 cells. The CDK7-selective inhibitor BS-181 partially rescued cell killing induced by 72-hour treatment of triptolide, which may be due to partial rescue of RPB1 degradation. We suggest that a precise phosphorylation site on RPB1 (Ser1878) was phosphorylated by CDK7 in response to triptolide. In addition, XPB and p44, two transcription factor TFIIH subunits, did not contribute to triptolide-driven RPB1 degradation and cell killing, although XPB was reported to covalently bind to triptolide. Several clinical trials are underway to test triptolide and its analogues for treating cancer and other diseases, so our data may help expand potential clinical uses of triptolide, as well as offer a compound that overcomes tumor MDR. Future investigations into the primary molecular target(s) of triptolide responsible for RPB1 degradation may suggest novel anti-MDR target(s) for therapeutic development. Mol Cancer Ther; 15(7); 1495-503. (c)2016 AACR. PMID- 27197305 TI - Targeted Drug Delivery with an Integrin-Binding Knottin-Fc-MMAF Conjugate Produced by Cell-Free Protein Synthesis. AB - Antibody-drug conjugates (ADC) have generated significant interest as targeted therapeutics for cancer treatment, demonstrating improved clinical efficacy and safety compared with systemic chemotherapy. To extend this concept to other tumor targeting proteins, we conjugated the tubulin inhibitor monomethyl-auristatin-F (MMAF) to 2.5F-Fc, a fusion protein composed of a human Fc domain and a cystine knot (knottin) miniprotein engineered to bind with high affinity to tumor associated integrin receptors. The broad expression of integrins (including alphavbeta3, alphavbeta5, and alpha5beta1) on tumor cells and their vasculature makes 2.5F-Fc an attractive tumor-targeting protein for drug delivery. We show that 2.5F-Fc can be expressed by cell-free protein synthesis, during which a non natural amino acid was introduced into the Fc domain and subsequently used for site-specific conjugation of MMAF through a noncleavable linker. The resulting knottin-Fc-drug conjugate (KFDC), termed 2.5F-Fc-MMAF, had approximately 2 drugs attached per KFDC. 2.5F-Fc-MMAF inhibited proliferation in human glioblastoma (U87MG), ovarian (A2780), and breast (MB-468) cancer cells to a greater extent than 2.5F-Fc or MMAF alone or added in combination. As a single agent, 2.5F-Fc MMAF was effective at inducing regression and prolonged survival in U87MG tumor xenograft models when administered at 10 mg/kg two times per week. In comparison, tumors treated with 2.5F-Fc or MMAF were nonresponsive, and treatment with a nontargeted control, CTRL-Fc-MMAF, showed a modest but not significant therapeutic effect. These studies provide proof-of-concept for further development of KFDCs as alternatives to ADCs for tumor targeting and drug delivery applications. Mol Cancer Ther; 15(6); 1291-300. (c)2016 AACR. PMID- 27197306 TI - Inhibition of PI3K/BMX Cell Survival Pathway Sensitizes to BH3 Mimetics in SCLC. AB - Most small cell lung cancer (SCLC) patients are initially responsive to cytotoxic chemotherapy, but almost all undergo fatal relapse with progressive disease, highlighting an urgent need for improved therapies and better patient outcomes in this disease. The proapoptotic BH3 mimetic ABT-737 that targets BCL-2 family proteins demonstrated good single-agent efficacy in preclinical SCLC models. However, so far clinical trials of the BH3 mimetic Navitoclax have been disappointing. We previously demonstrated that inhibition of a PI3K/BMX cell survival signaling pathway sensitized colorectal cancer cells to ABT-737. Here, we show that SCLC cell lines, which express high levels of BMX, become sensitized to ABT-737 upon inhibition of PI3K in vitro, and this is dependent on inhibition of the PI3K-BMX-AKT/mTOR signaling pathway. Consistent with these cell line data, when combined with Navitoclax, PI3K inhibition suppressed tumor growth in both an established SCLC xenograft model and in a newly established circulating tumor cell-derived explant (CDX) model generated from a blood sample obtained at presentation from a chemorefractory SCLC patient. These data show for the first time that a PI3K/BMX signaling pathway plays a role in SCLC cell survival and that a BH3 mimetic plus PI3K inhibition causes prolonged tumor regression in a chemorefractory SCLC patient-derived model in vivo These data add to a body of evidence that this combination should move toward the clinic. Mol Cancer Ther; 15(6); 1248-60. (c)2016 AACR. PMID- 27197307 TI - Irinotecan-Induced Gastrointestinal Dysfunction and Pain Are Mediated by Common TLR4-Dependent Mechanisms. AB - Strong epidemiological data indicate that chemotherapy-induced gut toxicity and pain occur in parallel, indicating common underlying mechanisms. We have recently outlined evidence suggesting that TLR4 signaling may contribute to both side effects. We therefore aimed to determine if genetic deletion of TLR4 improves chemotherapy-induced gut toxicity and pain. Forty-two female wild-type (WT) and 42 Tlr4 null (-/-) BALB/c mice weighing between 18 and 25 g (10-13 weeks) received a single 270 mg/kg (i.p.) dose of irinotecan hydrochloride or vehicle control and were killed at 6, 24, 48, 72, and 96 hours. Bacterial sequencing was conducted on cecal samples of control animals to determine the gut microbiome profile. Gut toxicity was assessed using validated clinical and histopathologic markers, permeability assays, and inflammatory markers. Chemotherapy-induced pain was assessed using the validated rodent facial grimace criteria, as well as immunologic markers of glial activation in the lumbar spinal cord. TLR4 deletion attenuated irinotecan-induced gut toxicity, with improvements in weight loss (P = 0.0003) and diarrhea (P < 0.0001). Crypt apoptosis was significantly decreased in BALB/c-Tlr4(-/-billy) mice (P < 0.0001), correlating with lower mucosal injury scores (P < 0.005). Intestinal permeability to FITC-dextran (4 kDa) and LPS translocation was greater in WT mice than in BALB/c-Tlr4(-/-billy) (P = 0.01 and P < 0.0001, respectively). GFAP staining in the lumbar spinal cord, indicative of astrocytic activation, was increased at 6 and 72 hours in WT mice compared with BALB/c-Tlr4(-/-billy) mice (P = 0.008, P = 0.01). These data indicate that TLR4 is uniquely positioned to mediate irinotecan-induced gut toxicity and pain, highlighting the possibility of a targetable gut/CNS axis for improved toxicity outcomes. Mol Cancer Ther; 15(6); 1376-86. (c)2016 AACR. PMID- 27197309 TI - Prediabetes in California: Nearly Half of California Adults on Path to Diabetes. AB - In California, more than 13 million adults (46 percent of all adults in the state) are estimated to have prediabetes or undiagnosed diabetes. An additional 2.5 million adults have diagnosed diabetes. Altogether, 15.5 million adults (55 percent of all California adults) have prediabetes or diabetes. Although rates of prediabetes increase with age, rates are also high among young adults, with one third of those ages 18-39 having prediabetes. In addition, rates of prediabetes are disproportionately high among young adults of color, with more than one-third of Latino, Pacific Islander, American Indian, African-American, and multiracial Californians ages 18-39 estimated to have prediabetes. Policy efforts should focus on reducing the burden of prediabetes and diabetes through support for prevention and treatment. PMID- 27197311 TI - Taking the Bite out of Zika. PMID- 27197308 TI - A New Triglycyl Peptide Linker for Antibody-Drug Conjugates (ADCs) with Improved Targeted Killing of Cancer Cells. AB - A triglycyl peptide linker (CX) was designed for use in antibody -: drug conjugates (ADC), aiming to provide efficient release and lysosomal efflux of cytotoxic catabolites within targeted cancer cells. ADCs comprising anti epithelial cell adhesion molecule (anti-EpCAM) and anti-EGFR antibodies with maytansinoid payloads were prepared using CX or a noncleavable SMCC linker (CX and SMCC ADCs). The in vitro cytotoxic activities of CX and SMCC ADCs were similar for several cancer cell lines; however, the CX ADC was more active (5-100 fold lower IC50) than the SMCC ADC in other cell lines, including a multidrug resistant line. Both CX and SMCC ADCs showed comparable MTDs and pharmacokinetics in CD-1 mice. In Calu-3 tumor xenografts, antitumor efficacy was observed with the anti-EpCAM CX ADC at a 5-fold lower dose than the corresponding SMCC ADC in vivo Similarly, the anti-EGFR CX ADC showed improved antitumor activity over the respective SMCC conjugate in HSC-2 and H1975 tumor models; however, both exhibited similar activity against FaDu xenografts. Mechanistically, in contrast with the charged lysine-linked catabolite of SMCC ADC, a significant fraction of the carboxylic acid catabolite of CX ADC could be uncharged in the acidic lysosomes, and thus diffuse out readily into the cytosol. Upon release from tumor cells, CX catabolites are charged at extracellular pH and do not penetrate and kill neighboring cells, similar to the SMCC catabolite. Overall, these data suggest that CX represents a promising linker option for the development of ADCs with improved therapeutic properties. Mol Cancer Ther; 15(6); 1311-20. (c)2016 AACR. PMID- 27197310 TI - Unequal Protection: Secondhand Smoke Threatens Health of Tenants in Multi-Unit Housing in Los Angeles. AB - Secondhand smoke is dangerous to a person's health at any level of exposure. Yet policies that prevent smoking are not in place for a majority of market-rate multi-unit housing complexes, according to a new survey of nearly 1,000 apartment dwellers in the city of Los Angeles. Approximately 37 percent of respondents reported that secondhand smoke had drifted into their apartments in the past year. Households with members of vulnerable populations, such as children or individuals with chronic conditions, are more likely to report smoke drifting from adjacent units. Four out of five respondents--including more than half of those who self-reported currently smoking--supported a smoke-free policy in common areas and/or individual units. PMID- 27197312 TI - Protecting Patients. PMID- 27197313 TI - Medical Alerts Get a Makeover. PMID- 27197314 TI - What You Don't Know About Your Doctor Could Hurt You. PMID- 27197316 TI - Taking Drugs Off the Menu. PMID- 27197315 TI - A Safer Food Future, Now. PMID- 27197317 TI - A Safer Chicken in Every Pot. PMID- 27197318 TI - My allergies are awful. Apart from medication, what can I do in my house to ease the misery? PMID- 27197319 TI - Pain Relief Now! PMID- 27197321 TI - [Not Available]. PMID- 27197320 TI - Defining the Role of a Pediatric Surgery Fellowship Program Director: Results of a National Cross-sectional Survey. PMID- 27197322 TI - [Food allergy in children: a diagnostic challenge]. AB - Food allergy in children has increased unexpectedly during the last decades and is now the leading cause of anaphylaxis in Europe. The impact on quality of life is significant; a reliable diagnosis is therefore of critical importance. The diagnostic approach includes an initial clinical evaluation followed by allergy testing (in vivo and/or in vitro). Determination of molecular allergens (recombinants) has emerged as a complementary tool in the diagnosis of food allergy allowing a better prediction of systemic reactions and identifying markers of persistence or resolution. With recent developments, a more proactive approach is being adopted, which includes oral food challenges in order to avoid unnecessary exclusions. PMID- 27197323 TI - [Drug reaction with eosinophilia and systemic symptoms]. AB - Cutaneous drug eruptions are delayed type hypersensitivity reactions that can be potentially life threatening. Severe cutaneous adverse reactions encompass the acute generalized exanthematous pustulosis (AGEP), the drug reaction with eosinophilia and systemic symptoms (DRESS), the Stevens-Johnson syndrome (SJS) and the toxic epidermal necrolysis (TEN, synonym: Lyell syndrome). In this article, we focus on the DRESS syndrome, which associates skin eruption and systemic symptoms. Its mortality rate is estimated at 10%. Therefore early diagnosis and the interruption of the culprit drug are crucial. In this review, we discuss the physiopathology, the most common eliciting drugs, the diagnostic criteria and the proposed treatments of DRESS. PMID- 27197324 TI - [If you go looking for trouble you'll find it. Urticarial reactions to insects of our local areas]. AB - Itchy skin rashes are a frequent reason to seek medical advice. The symptoms may be caused by hypersensitivity reactions to arthropod bites, waterborne parasites or setae from moth caterpillars and are sometimes mistaken for spontaneous urticaria or eczema. Some of these pests are resurging in Switzerland and elsewhere and increasingly responsible for emergency consultation. In this article we review itchy skin rashes caused by bed bugs, scabies, lice, cercariae, Pyemotes spp, caterpillars and harvest mites, which may be confounded with urticaria and allergic contact dermatitis. We detail here clinical manifestations, topographical distribution of skin lesions, epidemiology, treatment and preventive measures. PMID- 27197325 TI - [Sjogren's syndrome: when to suspect and how to confirm?]. AB - Sjogren's syndrome (SS) is an autoimmune disease leading to mucosal dryness. It may also involve joints, nerves, kidneys and lungs. Patients with SS are also at increased risk for lymphoma. Diagnosis of SS relies on clinical, biological, histological and radiological criteria, after exclusion of other causes. Initial work-up may be performed in general practice, by serology (antinuclear and anti SSA/SSB antibodies, rheumatoid factor) and by measuring lacrimal and salivary flow. Antibodies may be within normal range in up to one third of patients and when present are not specific for SS. Histological proof of lymphocytic sialadenitis is precious but invasive. Major salivary glands sonography may help select candidates for labial biopsy. This article elaborates the steps to be taken in case of suspected SS, in order to facilitate early diagnosis. PMID- 27197326 TI - [Whipple disease: a differential diagnosis of polyarthritis to keep in mind]. AB - Whipple disease is a rare and potentially fatal bacterial infection induced by a Gram-positive bacillus, Tropheryma whipplei. It is responsible for articular, digestive, neurological, ophthalmological and cardiological symptoms that occur either concomitant or isolated. Thus, the diagnosis is difficult to make and therefore often delayed. A paradoxal exacerbation of the symptoms under immunosuppressive drugs such as glucocorticoids and anti-TNF mAb, or inexpected improvements under antibiotic treatment applied for other reasons should raise a clinicial suspicion of Whipple's disease. Detection of the germ on stool and saliva samples by molecular biology methods has become straightforward with very good positive and negative predictive values. Long-term antibiotic treatment close follow-up are required for the induction of remission and to recognize relapse. PMID- 27197328 TI - [Not Available]. PMID- 27197327 TI - [Understanding primary immunodeficiencies: usefulness of a register]. AB - Primary Immunodeficiency Diseases (PID) comprise inborn defects of the immune system which are and therefore difficult to study For this reason, the European Society for ImmunoDeficiencies (ESID) has set up an internet-based international patient and research database which integrates research data with more detailed clinical information. These disorders are not only found in children, but also in adults resulting in a wide range of clinical manifestations. Primary immunodeficiency adults are much less known and may remain undiagnosed. PMID- 27197329 TI - [Not Available]. PMID- 27197330 TI - [Not Available]. PMID- 27197331 TI - [Not Available]. PMID- 27197332 TI - [Not Available]. PMID- 27197333 TI - [Not Available]. PMID- 27197334 TI - [Not Available]. PMID- 27197335 TI - [Not Available]. PMID- 27197336 TI - Water--Our Most Precious Resource. PMID- 27197337 TI - Geographic Isolation and Social Support in Rural Wisconsin. PMID- 27197338 TI - The Effects of Geographic Isolation and Social Support on the Health of Wisconsin Women. AB - BACKGROUND: Rural residents are less likely to receive preventive health screening, more likely to be uninsured, and more likely to report fair to poor health than urban residents. Social disconnectedness and perceived isolation are known to be negative predictors of self-rated physical health; however, the direct effects of geographic isolation and social support on overall health have not been well elucidated. METHODS: A cross-sectional survey of women (n = 113) participating in Wisconsin Rural Women's initiative programming was conducted, which included measures of geographic isolation, an assessment of overall health, and social support using the validated Interpersonal Support Evaluation List with 3 subscales, including belonging support, tangible support, and appraisal support. RESULTS: Geographic isolation was shown to be a negative predictor of belonging support (P = .0064) and tangible support (P = .0349); however, geographic isolation was not a statistically significant predictor of appraisal support. A strong and direct relationship was observed between social support and self-perceived health status among this population of Wisconsin women, and hospital access based on geographic proximity was positively correlated (P = .028) with overall health status. CONCLUSIONS: The direct relationship between social support and overall health demonstrated here stresses the importance of developing and maintaining strong social support networks, which can be improved through rural support groups that have the unique ability to assist rural residents in fostering social support systems, advocating stress management techniques, and achieving a greater sense of well-being. PMID- 27197339 TI - Cystectomy and Urinary Diversion for the Management of a Devastated Lower Urinary Tract Following Prostatic Cryotherapy and/or Radiotherapy. AB - INTRODUCTION: We investigated the outcomes and quality of life measures in men who underwent cystectomy and urinary diversion for devastating lower urinary tract toxicity after prostatic radiotherapy and/or cryotherapy for the treatment of prostate cancer. METHODS: Records of patients who underwent cystectomy and urinary diversion for the management of a devastated lower urinary tract following prostatic radiotherapy or cryotherapy were reviewed retrospectively. A postoperative, retrospective quality of life (QOL) survey was designed specific to this patient subset and obtained by telephone interview. RESULTS: Extirpative surgery with urinary diversion for management of a devastated lower urinary tract was performed on 15 patients with a mean age of 72 years (range 63-82). Toxicities leading to bladder removal included bladder neck contractures, prostatic necrosis, incontinence, osteomyelitis, bladder calculi, fistulae, urethral strictures, abscesses, necrotizing fasciitis, and radiation/hemorrhagic cystitis. The mean number of failed conservative, minimally invasive interventions per patients prior to cystectomy was 3.7 (range 1-12). The average time period from major complication following radiotherapy/cryotherapy to cystectomy was 29.1 months (range 5-65). The QOL survey showed all of the patients who completed the survey (n = 13) would undergo the procedure again and 11 (85%) would have undergone the procedure an average of 13.2 months sooner (range 5-36). CONCLUSION: Toxicities secondary to prostatic radiotherapy or cryotherapy may be debilitating. Our results demonstrate that cystectomy with urinary diversion can improve QOL in patients with a devastated lower urinary tract. PMID- 27197341 TI - Students' Critical Incidents Point the Way to Safer Patient Care Transitions. AB - INTRODUCTION: Patient care transitions are prevalent in health care, and faulty transition-related communications are associated with 80% of serious medical errors. While medical student curricula on care transitions are increasing, there are limited evaluation reports and little guidance on primary care transition training. METHODS: The Medical College of Wisconsin initiated an annual 2-hour patient care transition intersession for third-year medical students. The intersession used a critical incident report, where students wrote about a recent, de-identified patient transition they witnessed that evoked in them "a strong emotional reaction." Next, intersession training included a novel, structured communication handoff mnemonic. At the intersession conclusion, students wrote what they would do differently if their critical incident transition occured in the future. Evaluations (2010-2014) consisted of students' post-session reactions and learning. Authors completed a detailed, qualitative analysis of students' critical incident reports from the 2010 intersession. RESULTS: Students reacted positively to all intersession elements, especially clinician-led, small-group discussions. Student reports revealed that over 90% of their critical incident evoked negative emotional reactions (eg, frustrated, disappointed, helpless). Post-intersession, 86% of students reported intentions to adopt new strategies to improve future care transitions, and 38% referenced components of the learned mnemonic. CONCLUSION: Medical students reacted positively to this intersession, especially small-group discussions. Students revealed mostly negative emotions from their critical incident on patient handoffs, but they gained effective strategies for future handoff communications. Authors recommend continued use of the handoff mnemonic, with greater attention to training environments that emphasize patient and learner safety. PMID- 27197340 TI - Prevention of Perinatal Transmission of Hepatitis B Virus: Assessment Among Wisconsin Maternity Hospitals. AB - PURPOSE: To evaluate the completeness of identification of pregnant women testing positive for hepatitis B surface antigen (HBsAg) and birth dose hepatitis B vaccine administration, and the extent of appropriate prophylaxis of infants born to women with and without maternal HBsAg status documented in the infant medical record. METHODS: We conducted medical record reviews of 3058 maternal and infant pairs at 58 Wisconsin maternity hospitals that cumulatively delivered 90% of Wisconsin's 2010 birth cohort. RESULTS: A documented HBsAg test result for the current pregnancy was included in 2928 (95.7%) of maternal records, and in 2676 (87.5%) infant records. Four infants (15%) were born to HBsAg-positive women; all 4 infants received appropriate prophylaxis: hepatitis B immunoglobulin (HBIG) and a dose of hepatitis B vaccine within 12 hours of birth. However, among 382 infants without a documented maternal HBsAg test result in the infant medical record, only 135 (35%) received appropriate prophylaxis: a dose of hepatitis B vaccine within 12 hours of birth or a dose of hepatitis B vaccine and HBIG within 12 hours of birth for infants weighing < 2000 g. Among all infants, 81.6% received hepatitis B vaccine prior to hospital discharge. CONCLUSIONS: Hospitals must ensure that infants without a documented maternal HBsAg test result receive appropriate prophylaxis to prevent hepatitis B vaccine infection. All infants, regardless of maternal HBsAg test result, should receive a dose of hepatitis B vaccine before hospital discharge to serve as a "safety net" to prevent infection among infants born to HBsAg-positive women who are not identified prenatally. A written hospital policy for universal hepatitis B vaccine birth dose administration should be developed to reinforce admission orders. PMID- 27197342 TI - Medical Student Mock Interviews to Improve Residency Interviewing and Match Success. AB - PURPOSE: Using a quasi-experimental approach, we examined student and faculty satisfaction with a mock residency interview program. We also examined whether self-selected participants had match rates that differed from nonparticipants. METHODS: Interviews were arranged on a specified evening between students and a physician in the specialty to which the student wished to apply. Interviews were structured as similarly to residency interviews as possible, but included 10 minutes of verbal feedback and subsequent written feedback to all students. Students completed surveys indicating their satisfaction with the mock interview immediately following the interview and 5 months later (after their actual resident interviews). Faculty feedback to students and their satisfaction with the program also was collected. Out of 189 (55%) students in the senior class, 104 volunteered to participate. RESULTS: Immediately following the mock interview, over 90% of students who participated either strongly agreed or agreed that the interview feedback was helpful, seemed realistic, and helped them identify strengths and weaknesses. Responses collected 5 months later were still favorable, but less positive. Faculty identified 7 students who they believed had poor interview techniques and an additional 13 who interviewers believed would be unlikely to match in their specialty. Final match results for the group participating in the mock interview showed a primary match rate of 99%, which was higher than students who did not participate (94%, P < .001). CONCLUSION: In a self-selected group of students who chose to participate, mock interviews were useful in improving student match success compared to students who did not participate in the mock interview program. Because all students were not required to participate, it is unclear whether this tactic would be successful for all students. PMID- 27197343 TI - Bowel Perforation Associated With Infliximab Use in a Pediatrics Patient. AB - Crohn's disease (CD) is an idiopathic inflammatory disease of the gastrointestinal tract and typically causes inflammation with granuloma formation. Biologic agents like infliximab (IFX) that target tumor necrosis factor alpha (TNF-alpha), have emerged as important medications for treating refractory CD. With increasing use, there also are reports of rare but potentially fatal complications associated with exposure to TNF-alpha, such as bowel perforation. We present a case report of spontaneous bowel perforation in a child with Crohn's while on IFX therapy, and a review of the current literature. The purpose of this report is to alert physicians to this rare association, especially in pediatric patients with intestinal strictures. PMID- 27197344 TI - Removal of Endobronchially Placed Vascular Self-Expandable Metallic Stent Using Flexible Bronchoscopy. AB - Self-expanding metallic stents (SEMS) are commonly placed in malignant airway obstruction and sometimes in benign obstruction. Complications from SEMS placement are common, especially after 30 days from deployment. SEMS removal can be complicated and often involves significant resources. We report a case of a 78 year-old man with small cell carcinoma who underwent placement of a Luminexx endovascular stent in his right main stem bronchus, complicated by stent migration after initiation of chemotherapy. Stent removal was performed by flexible bronchoscopy, utilizing forceps inserted via a working channel, as well as a goose neck snare operated parallel to the bronchoscope. The patient was discharged the same day with no complications. PMID- 27197345 TI - Small Cell Carcinoma of the Gall Bladder. AB - Small cell carcinoma of the gall bladder (SCCGB) is a rare condition, with only 53 prior cases reported in the world literature when our case was first diagnosed. Our patient was found to have limited stage disease and was treated with sequential laparoscopic cholecystectomy, etoposide/carboplatin chemotherapy followed by consolidating loco-regional radiation therapy. She is alive and well without evidence of disease more than 132 months since diagnosis. We describe here our experience in the diagnosis, staging workup, treatment, and surveillance of a case of SCCGB and review the published literature. Treated aggressively with currently available methods, patients with limited stage SCCGB can have an excellent prognosis. The authors' intent is to provide a reasonable plan of treatment for other physicians facing such an unusual patient. PMID- 27197346 TI - One UW Health. PMID- 27197347 TI - Statewide Blood Pressure Improvement Challenge. PMID- 27197348 TI - Making Environmental Health Indispensable. PMID- 27197350 TI - The Investigation of Groundwater Contamination in Wicomico County's Morris Mill Community. AB - In 2012, the Wicomico County Health Department began investigating groundwater contamination in the Morris Mill community. The contamination was due to high levels of trichloroethylene (TCE). TCE is a colorless nonflammable liquid that has a sweet odor and a burning taste. Exposures can lead to acute effects as well as more chronic conditions such as cancer. A total of 300 wells were sampled during the course of the investigation. Fifty wells showed levels of TCE above the maximum contaminant level of 5 parts per billion. Timely communication with the residents and risk management played integral parts in assisting the community towards a long-term solution. In December 2013, the Wicomico County Urban Services Commission created an urban service district to provide public water from the city of Fruitland to the entire affected area. Completion of the water tower and distribution system for the 273 affected homes was expected in early 2016. PMID- 27197349 TI - Formaldehyde Levels in Traditional and Portable Classrooms: A Pilot Investigation. AB - The pilot study discussed in this article assessed formaldehyde levels in portable classrooms (PCs) and traditional classrooms the authors evaluated formaldehyde levels in day and overnight indoor air (TCs) and explored factors influencing indoor air quality (e.g., carbon dioxide, temperature, and relative humidity). In a cross-sectional design, samples from nine PCs renovated within three years previously and three TCs in a school district in metropolitan Atlanta, Georgia. Formaldehyde levels ranged from 0.0068 to 0.038 parts per million (ppm). In both types of classroom, overnight formaldehyde median levels (PCs = 0.018 ppm; TCs = 0.019 ppm) were higher than day formaldehyde median levels (PCs = 0.011 ppm; TCs = 0.016 ppm). Carbon dioxide levels measured 470-790 ppm at 7:00 a.m. and 470-1800 ppm at 4:00 p.m. Afternoon medians were higher in TCs (1,400 ppm) than in PCs (780 ppm). Consistent with previous studies, formaldehyde levels were similar among PCs and TCs. Reducing carbon dioxide levels by improving ventilation is recommended for classrooms. PMID- 27197351 TI - Poor Indoor Air Quality, Mold Exposure, and Upper Respiratory Tract Infections- Are We Placing Our Children at Risk? AB - Understanding how respiratory health risks are associated with poor housing is essential to designing effective strategies to improve children's quality of life. The objective of the study described in this article was to determine the relationship between respiratory health and housing conditions. A survey was completed by 3,424 parents of children in third and fourth grade in Winnipeg, Manitoba, Canada. An engineering audit and air samples were also taken in the homes of a subset of 715 homes. Results showed that a child's respiratory health is significantly associated with self-reported visible mold in the home and that a significant association existed between occupant-reported visible mold and tested airborne mold. Findings highlight the need for clearer standards of acceptable CFU/m3 limits for mold genera that are applicable to homes. In the absence of such guidelines, problems associated with indoor mold will continue to impact the health of residents, despite growing evidence of the adverse effects from mold exposure. PMID- 27197353 TI - Collaborating to Solve Complex Environmental Health Issues in Our Communities. PMID- 27197352 TI - NEHA/UL Sabbatical Exchange Program Report: To Glove or Not to Glove? PMID- 27197354 TI - CDC's Drought Guidance: Your Public Health Resource for Understanding and Preparing for Drought in Your Community. PMID- 27197355 TI - Environmental Health Tracking Rides the Open Data Wave. PMID- 27197356 TI - Environmental Health 2.0. PMID- 27197357 TI - Transitions. PMID- 27197358 TI - The Bernie Sanders Health Care Plan--Viable? PMID- 27197359 TI - Instructions and Explanations--Do Your Patients Understand Yours? PMID- 27197360 TI - Eye Safety in Dentistry and Associated Liability. AB - The first objective of this article is to expressan experimental-work-supported opinion ofits authors regarding the inadequacy of thepresent dental mask and regular eyewearcombination for protecting dental care practitioners. Its second objective is to suggestamending OSHA Standard 1910.133(a)(1) tomandate effective eye protection for dentalcare practitioners by requiring the use ofeffective means for closing the bottom gapsbetween the lower rims of the lenses of theprotective eyewear and the upper edge ofthe mask worn by the practitioner.The various types and sources of dentalpractice eye occupational hazards and thepossible entry routes of dental debris towarddental practitioners'eyes are discussed.Experimental work, confirming theinadequacy of the present dental mask andeyewear combination for protecting dentalcare practitioners, is presented. PMID- 27197361 TI - Substance Abuse and Tooth Destruction. PMID- 27197362 TI - Dental Practice as the Population Demographics Change in Massachusetts. AB - General population demographics in the United States, individual states, and counties are undergoing dramatic changes. Long-term customary populations, which provided the bulwark for many successful dental practices, are being replaced by the many minority populations (in particular, the Hispanic population), foreign born residents, and many for whom English may not be their first language. These developments are reviewed for the Commonwealth of Massachusetts and its counties in an effort to challenge practitioners by the extent of these developments. PMID- 27197363 TI - A New Integrated Oral Health and Primary Care Education Program in the Dental Student Clinic. AB - OBJECTIVES: The purpose of the study was to describe the implementation of a new program incorporating primary care education into a predoctoral dental curriculum in the StudentTeaching Clinic at Harvard School of Dental Medicine (HSDM) using the primary care rotations for students in a dental setting as a platform for change in our approach to patient care. METHODS: A survey of perspectives on the need for primary care medicine in dental education was distributed to all the deans of Commission on Dental Accreditation (CODA)-accredited dental schools in the continental United States for a total of 65 eligible schools. RESULTS: Of the 27 responses from the dental school deans, a majority of dental schools already had interprofessional collaborative practices at their schools, with collaborations with physicians and nurse practitioners being most common. Ninety six percent of responders were supportive of integrating oral health and primary care to improve patient care and regarded primary care training for dental students as a potential method of improving patient care in dental education. CONCLUSION: As patient care involves multidisciplinary and interprofessional environments with a wide array of health care providers, curricular directions for dental school should explore an education model that incorporates the concepts of primary care medicine. PMID- 27197364 TI - A Clinico-Pathologic Correlation. Clinician's corner. Florid cement-osseous dysplasia. PMID- 27197366 TI - Articulating our views. PMID- 27197365 TI - Enlargement of the Inferior Alveolar Canal. PMID- 27197367 TI - A casualty of the Rising. PMID- 27197368 TI - Science of the times. PMID- 27197369 TI - There's no such thing as a quick fix. PMID- 27197371 TI - Three case reports demonstrating treatment of relatively complex orthodontic cases using a completely customised lingual appliance. AB - It is a commonly held misconception among Irish dentists that only minor malocclusions can be treated with lingual appliances. This article demonstrates the use of contemporary completely customised lingual orthodontic appliances to treat a diverse range of malocclusions, to a satisfactory level, and thereby may disabuse clinicians of the belief that only minor malocclusions can be treated with lingual appliances. PMID- 27197370 TI - Articulators, face bows and interocclusal records. PMID- 27197372 TI - The path of least resistance in oral surgery. AB - STATEMENT OF THE PROBLEM: Antibiotic resistance is an imminent threat to worldwide public health. Dental professionals must demonstrate judicious use of antibiotics and educate their patients about the risks associated with their overuse. PURPOSE OF THE PAPER: To encourage the dental profession to prescribe responsibly in order to optimise the use of antibiotics in oral surgery. Antibiotic stewardship programmes are recommended to help reduce the emergence of infections that are multidrug-resistant. Clinical practice audits are encouraged to help dentists ensure conservative prescribing patterns. CONCLUSIONS: The dental profession has a duty of care to prescribe antibiotics in adherence with current best practice oral surgery guidelines. The dental profession must show leadership in slowing antibiotic resistance by pledgina to safeguard their appropriate use. PMID- 27197373 TI - A passionate advocate. PMID- 27197374 TI - Opinion overlooks profit motive for taking X-rays. PMID- 27197375 TI - We need to embrace change to thrive. PMID- 27197376 TI - Brush up on your business skills. PMID- 27197378 TI - Mentors show us the way. PMID- 27197377 TI - Be wary hiring a management company. PMID- 27197379 TI - Updated Dental Practice Act expands auxiliary duties. PMID- 27197380 TI - Janov Barry treasures the golden era of radio. PMID- 27197381 TI - Your patients and profession need you. PMID- 27197382 TI - Temporal variability in aboveground plant biomass decreases as spatial variability increases. AB - Ecological theory predicts that diversity decreases variability in ecosystem function. We predict that, at the landscape scale, spatial variability created by a mosaic of contrasting patches that differ in time since disturbance will decrease temporal variability in aboveground plant biomass. Using data from a multi-year study of seven grazed tallgrass prairie landscapes, each experimentally managed for one to eight patches, we show that increased spatial variability driven by spatially patchy fire and herbivory reduces temporal variability in aboveground plant biomass. This pattern is associated with statistical evidence for the portfolio effect and a positive relationship between temporal variability and functional group synchrony as predicted by metacommunity variability theory. As disturbance from fire and grazing interact to create a shifting mosaic of spatially heterogeneous patches within a landscape, temporal variability in aboveground plant biomass can be dampened. These results suggest that spatially heterogeneous disturbance regimes contribute to a portfolio of ecosystem functions provided by biodiversity, including wildlife habitat, fuel, and forage. We discuss how spatial patterns of disturbance drive variability within and among patches. PMID- 27197383 TI - Does ecosystem sensitivity to precipitation at the site-level conform to regional scale predictions?. AB - Central to understanding global C cycle dynamics is the functional relationship between precipitation and net primary production (NPP). At large spatial (regional) scales, the responsiveness of aboveground NPP (ANPP) to interannual variation in annual precipitation (AP; ANPPsens) is inversely related to site level ANPP, coinciding with turnover of plant communities along precipitation gradients. Within ecosystems experiencing chronic alterations in water availability, plant community change will also occur with unknown consequences for ANPPsens. To examine the role plant community shifts may play in determining alterations in site-level ANPPPsens, we experimentally increased precipitation by approximately 35% for two decades in a native Central U.S. grassland. Consistent with regional models, ANPPsens decreased initially as water availability and ANPP increased. However, ANPPsens shifted back to ambient levels when mesic species increased in abundance in the plant community. Similarly, in grassland sites with distinct mesic and xeric plant communities and corresponding 50% differences in ANPP, ANPPsens did not differ over almost three decades. We conclude that responses in ANPPsens to chronic alterations in water availability within an ecosystem may not conform to regional AP-ANPP patterns, despite expected changes in ANPP and plant communities. The result is unanticipated functional resistance to climate change at the site scale. PMID- 27197384 TI - Propagule size and dispersal costs mediate establishment success of an invasive species. AB - Bio-invasions depend on the number and frequency of invaders arriving in new habitats. Yet, as is often the case, it is not only quantity that counts, but also quality. The process of dispersal can change disperser quality and establishment success. Invasions are a form of extra-range dispersal, so that invaders often experience changes in quality through dispersal. To study effects of dispersal on invader quality, and its interactions with quantity on invasion success, we manipulated both in a field experiment using an invasive marine invertebrate. Establishment success increased with the number of individuals arriving in a new habitat. Prolonged larval durations--our manipulation of prolonged dispersal--decreased individual quality and establishment success. Groups of invaders with prolonged larval durations contributed only a third of the offspring relative to invaders that settled immediately. We also found an interaction between the quality and quantity of invaders on individual growth: only within high-quality cohorts did individuals experience density-dependent effects on growth. Our findings highlight that dispersal not only affects the quantity of invaders arriving in a new habitat but also their quality, and both mediate establishment success. PMID- 27197385 TI - Estimating where and how animals travel: an optimal framework for path reconstruction from autocorrelated tracking data. AB - An animal's trajectory is a fundamental object of interest in movement ecology, as it directly informs a range of topics from resource selection to energy expenditure and behavioral states. Optimally inferring the mostly unobserved movement path and its dynamics from a limited sample of telemetry observations is a key unsolved problem, however. The field of geostatistics has focused significant attention on a mathematically analogous problem that has a statistically optimal solution coined after its inventor, Krige. Kriging revolutionized geostatistics and is now the gold standard for interpolating between a limited number of autocorrelated spatial point observations. Here we translate Kriging for use with animal movement data. Our Kriging formalism encompasses previous methods to estimate animal's trajectories--the Brownian bridge and continuous-time correlated random walk library--as special cases, informs users as to when these previous methods are appropriate, and provides a more general method when they are not. We demonstrate the capabilities of Kriging on a case study with Mongolian gazelles where, compared to the Brownian bridge, Kriging with a more optimal model was 10% more precise in interpolating locations and 500% more precise in estimating occurrence areas. PMID- 27197386 TI - Linking multidimensional functional diversity to quantitative methods: a graphical hypothesis--evaluation framework. AB - Functional trait analysis is an appealing approach to study differences among biological communities because traits determine species' responses to the environment and their impacts on ecosystem functioning. Despite a rapidly expanding quantitative literature, it remains challenging to conceptualize concurrent changes in multiple trait dimensions ("trait space") and select quantitative functional diversity methods to test hypotheses prior to analysis. To address this need, we present a widely applicable framework for visualizing ecological phenomena in trait space to guide the selection, application, and interpretation of quantitative functional diversity methods. We describe five hypotheses that represent general patterns of responses to disturbance in functional community ecology and then apply a formal decision process to determine appropriate quantitative methods to test ecological hypotheses. As a part of this process, we devise a new statistical approach to test for functional turnover among communities. Our combination of hypotheses and metrics can be applied broadly to address ecological questions across a range of systems and study designs. We illustrate the framework with a case study of disturbance in freshwater communities. This hypothesis-driven approach will increase the rigor and transparency of applied functional trait studies. PMID- 27197387 TI - Synthesis: comparing effects of resource and consumer fluxes into recipient food webs using meta-analysis. AB - Here we synthesize empirical research using meta-analysis to compare how consumer and resource fluxes affect recipient food webs. We tested the following hypotheses: (H1) The direct effects of resource fluxes (bottom-up) should be stronger than the direct effects of consumer fluxes (top-down), because resource fluxes are permanent (do not return to the food web in which they were produced) but consumer fluxes may not be (consumers can leave). (H2) Following H1, the indirect effects should attenuate (weaken) more quickly for consumer fluxes than for resource fluxes due to their direct effects being weaker, (H3) The effects of resource fluxes should be stronger when recipient food webs are in different ecosystems than donor food webs due to differences in elevation that accompany cross-ecosystem food web interfaces, often increasing flux quantity due to gravity, while the effects of consumer fluxes should be stronger when donor and recipient food webs are in the same ecosystem as they should more easily assimilate into the recipient food web. We found no differences in the magnitude of bottom-up and top-down direct effects for resource and consumer fluxes, but top-down direct effects were 122% stronger than top-down indirect effects. Indirect effects of prey and predator fluxes quickly attenuated while indirect effects of non-prey resource and herbivore fluxes did not, as the overall direct effects of prey and predator fluxes were 123% and 163% stronger than their indirect effects, respectively. This result suggests that the magnitude of indirect effects decrease as the trophic level of resource and consumer fluxes increases, and also contrasts with results from studies showing in situ top-down indirect effects are stronger than in situ bottom-up indirect effects. We found that resource and consumer flux effect sizes were similar when they occurred between ecosystems, but when they occurred within ecosystems predator flux effects were 107% stronger than nutrient flux effects. Finally, we found that observational studies had higher effect sizes than manipulative studies. Future research should focus on how resource and consumer fluxes might interact and generate feedbacks in empirical studies of natural food webs, and what ecological factors might affect their relative strength. PMID- 27197388 TI - Belowground interactions with aboveground consequences: Invasive earthworms and arbuscular mycorrhizal fungi. AB - A mounting body of research suggests that invasive nonnative earthworms substantially alter microbial communities, including arbuscular mycorrhizal fungi (AMF). These changes to AMF can cascade to affect plant communities and vertebrate populations. Despite these research advances, relatively little is known about (1) the mechanisms behind earthworms' effects on AMF and (2) the factors that determine the outcomes of earthworm-AMF interactions (i.e., whether AMF abundance is increased or decreased and subsequent effects on plants). We predict that AMF-mediated effects of nonnative earthworms on ecosystems are nearly universal because (1) AMF are important components of most terrestrial ecosystems, (2) nonnative earthworms have become established in nearly every type of terrestrial ecosystem, and (3) nonnative earthworms, due to their burrowing and feeding behavior, greatly affect AMF with potentially profound concomitant effects on plant communities. We highlight the multiple direct and indirect effects of nonnative earthworms on plants and review what is currently known about the interaction between earthworms and AMF. We also illustrate how the effects of nonnative earthworms on plant-AMF mutualisms can alter the structure and stability of aboveground plant communities, as well as the vertebrate communities relying on these habitats. Integrative studies that assess the interactive effects of earthworms and AMF can provide new insights into the role that belowground ecosystem engineers play in altering aboveground ecological processes. Understanding these processes may improve our ability to predict the structure of plant and animal communities in earthworm-invaded regions and to develop management strategies that limit the numerous undesired impacts of earthworms. PMID- 27197389 TI - An allometric approach to quantify the extinction vulnerability of birds and mammals. AB - Methods to quantify the vulnerability of species to extinction are typically limited by the availability of species-specific input data pertaining to life history characteristics and population dynamics. This lack of data hampers global biodiversity assessments and conservation planning. Here, we developed a new framework that systematically quantifies extinction risk based on allometric relationships between various wildlife demographic parameters and body size. These allometric relationships have a solid theoretical and ecological foundation. Extinction risk indicators included are (1) the probability of extinction, (2) the mean time to extinction, and (3) the critical patch size. We applied our framework to assess the global extinction vulnerability of terrestrial carnivorous and non-carnivorous birds and mammals. Irrespective of the indicator used, large-bodied species were found to be more vulnerable to extinction than their smaller counterparts. The patterns with body size were confirmed for all species groups by a comparison with IUCN data on the proportion of extant threatened species: the models correctly predicted a multimodal distribution with body size for carnivorous birds and a monotonic distribution for mammals and non-carnivorous birds. Carnivorous mammals were found to have higher extinction risks than non-carnivores, while birds were more prone to extinction than mammals. These results are explained by the allometric relationships, predicting the vulnerable species groups to have lower intrinsic population growth rates, smaller population sizes, lower carrying capacities, or larger dispersal distances, which, in turn, increase the importance of losses due to environmental stochastic effects and dispersal activities. Our study is the first to integrate population viability analysis and allometry into a novel, process-based framework that is able to quantify extinction risk of a large number of species without requiring data-intensive, species-specific information. The framework facilitates the estimation of extinction vulnerabilities of data deficient species. It may be applied to forecast extinction vulnerability in response to a changing environment, by incorporating quantitative relationships between wildlife demographic parameters and environmental drivers like habitat alteration, climate change, or hunting. PMID- 27197390 TI - Genetic diversity affects the strength of population regulation in a marine fish. AB - Variation is an essential feature of biological populations, yet much of ecological theory treats individuals as though they are identical. This simplifying assumption is often justified by the perception that variation among individuals does not have significant effects on the dynamics of whole populations. However, this perception may be skewed by a historic focus on studying single populations. A true evaluation of the extent to which among individual variation affects the dynamics of populations requires the study of multiple populations. In this study, we examined variation in the dynamics of populations of a live-bearing, marine fish (black surfperch; Embiotoca jacksoni). In collaboration with an organization of citizen scientists (Reef Check California), we were able to examine the dynamics of eight populations that were distributed throughout approximately 700 km of coastline, a distance that encompasses much of this species' range. We hypothesized that genetic variation within a local population would be related to the intensity of competition and to the strength of population regulation. To test this hypothesis, we examined whether genetic diversity (measured by the diversity of mitochondrial DNA haplotypes) was related to the strength of population regulation. Low-diversity populations experienced strong density dependence in population growth rates and population sizes were regulated much more tightly than they were in high diversity populations. Mechanisms that contributed to this pattern include links between genetic diversity, habitat use, and spatial crowding. On average, low diversity populations used less of the available habitat and exhibited greater spatial clustering (and more intense competition) for a given level of density (measured at the scale of the reef). Although the populations we studied also varied with respect to exogenous characteristics (habitat complexity, densities of predators, and interspecific competitors), none of these characteristics was significantly related to the strength of population regulation. In contrast, an endogenous characteristic of the population (genetic diversity) explained 77% of the variation in the strength of population regulation (95% CI: 27-94%). Our results suggest that the genetic and phenotypic composition of populations can play a major role in their dynamics. PMID- 27197392 TI - Effects of individual, community, and landscape drivers on the dynamics of a wildland forest epidemic. AB - The challenges posed by observing host-pathogen-environment interactions across large geographic extents and over meaningful time scales limit our ability to understand and manage wildland epidemics. We conducted a landscape-scale, longitudinal study designed to analyze the dynamics of sudden oak death (an emerging forest disease caused by Phytophthora ramorum) across hierarchical levels of ecological interactions, from individual hosts up to the community and across the broader landscape. From 2004 to 2011, we annually assessed disease status of 732 coast live oak, 271 black oak, and 122 canyon live oak trees in 202 plots across a 275-km2 landscape in central California. The number of infected oak stems steadily increased during the eight-year study period. A survival analysis modeling framework was used to examine which level of ecological heterogeneity best predicted infection risk of susceptible oak species, considering variability at the level of individuals (species identity, stem size), the community (host density, inoculum load, and species richness), and the landscape (seasonal climate variability, habitat connectivity, and topographic gradients). After accounting for unobserved risk shared among oaks in the same plot, survival models incorporating heterogeneity across all three levels better predicted oak infection than did models focusing on only one level. We show that larger oak trees (especially coast live oak) were more susceptible, and that interannual variability in inoculum production by the highly infectious reservoir host, California bay laurel, more strongly influenced disease risk than simply the density of this important host. Concurrently, warmer and wetter rainy-season conditions in consecutive years intensified infection risk, presumably by creating a longer period of inoculum build-up and increased probability of pathogen spillover from bay laurel to oaks. Despite the presence of many alternate host species, we found evidence of pathogen dilution, where less competent hosts in species-rich communities reduce pathogen transmission and overall risk of oak infection. These results identify key parameters driving the dynamics of emerging infectious disease in California woodlands, while demonstrating how multiple levels of ecological heterogeneity jointly determine epidemic trajectories in wildland settings. PMID- 27197391 TI - Bottom-up and top-down human impacts interact to affect a protected coastal Chilean marsh. AB - Many ecosystems, even in protected areas, experience multiple anthropogenic impacts. While anthropogenic modification of bottom-up (e.g., eutrophication) and top-down (e.g., livestock grazing) forcing often co-occurs, whether these factors counteract or have additive or synergistic effects on ecosystems is poorly understood. In a Chilean bio-reserve, we examined the interactive impacts of eutrophication and illegal livestock grazing on plant growth with a 4-yr fertilization by cattle exclusion experiment. Cattle grazing generally decreased plant biomass, but had synergistic, additive, and antagonistic interactions with fertilization in the low, middle, and high marsh zones, respectively. In the low marsh, fertilization increased plant biomass by 112%, cattle grazing decreased it by 96%, and together they decreased plant biomass by 77%. In the middle marsh, fertilization increased plant biomass by 47%, cattle grazing decreased it by 37%, and together they did not affect plant biomass. In the high marsh, fertilization and cattle grazing decreased plant biomass by 81% and 92%, respectively, but together they increased plant biomass by 42%. These interactions were also found to be species specific. Different responses of plants to fertilization and cattle grazing were likely responsible for these variable interactions. Thus, common bottom-up and top-down human impacts can interact in different ways to affect communities even within a single ecosystem. Incorporating this knowledge into conservation actions will improve ecosystem management in a time when ecosystems are increasingly challenged by multiple interacting human impacts. PMID- 27197393 TI - Competition-mediated feedbacks in experimental multispecies epizootics. AB - Competition structures ecological communities and alters host-pathogen interactions. In environmentally transmitted pathogens, an infection-resistant competitor may influence infection dynamics in a susceptible species through the negative impacts of competition (e.g., by reducing host density or causing nutritional stress that increases susceptibility to infection) and/or the positive impacts of reducing transmission efficiency (e.g., by removing environmental pathogen stages). Thus, a non-susceptible competitor may enhance, reduce, or have no net effect on susceptible host density and infection prevalence. Here, we couple an epidemiological model with experimental epidemics to test how resource competition with a non-susceptible competitor (Daphnia pulicaria) influences fungal microparasite (Metschnikowia bicuspidata) infection dynamics in a susceptible host species (D. dentifera). Our model and experiments suggest that competitor density can mediate the direction and magnitude of the effect of competition on infection dynamics, with a peak in infection prevalence occurring at intermediate competitor densities. At low densities, the non susceptible competitor D. pulicaria may reduce infection prevalence in the susceptible host by removing fungal spores from the environment through feeding. However, when competitor density is increased and resources become limiting, D. pulicaria negatively impacts the susceptible host by increasing susceptible host feeding rates, and therefore fungal spore intake, and further by reducing susceptible host population size as it is driven toward competitive exclusion. In conclusion, these results show that a tradeoff between the competitor as a consumer of pathogen, which serves to reduce epidemic size, and as a modifier of susceptible host foraging ecology, which influences infection rates, may alternately enhance or dampen the magnitude of local epidemics. PMID- 27197394 TI - Seasonality and nitrogen supply modify carbon partitioning in understory vegetation of a boreal coniferous forest. AB - Given the strong coupling between the carbon (C) and nitrogen (N) cycles, there is substantial interest in understanding how N availability affects C cycling in terrestrial ecosystems, especially in ecosystems limited by N. However, most studies in temperate and boreal forests have focused on the effects of N addition on tree growth. By comparison, less is known about the effects of N availability on the cycling of C in understory vegetation despite some evidence that dwarf shrubs, mosses, and lichens play an important role in the forest C balance. In this study, we used an in situ 13CO2 pulse-labeling technique to examine the short-term dynamics of C partitioning in understory vegetation in three boreal Pinus sylvestris forest stands exposed to different rates of N addition: a low and high N addition that receive annual additions of NH4NO3 of 20 and 100 kg N/ha, respectively, and this is a typo. It should be an unfertilized control. Labeling was conducted at two distinct periods (early vs. late growing season), which provided a seasonal picture of how N addition affects C dynamics in understory vegetation. In contrast to what has been found in trees, there was no obvious trend in belowground C partitioning in ericaceous plants in response to N additions or seasonality. Increasing N addition led to a greater percentage of 13C being incorporated into ericaceous leaves with a high turnover, whereas high rates of N addition strongly reduced the incorporation of 13C into less degradable moss tissues. Addition of N also resulted in a greater percentage of the 13C label being respired back to the atmosphere and an overall reduction in total understory carbon use efficiency. Taken together, our results suggest a faster cycling of C in understory vegetation with increasing N additions; yet the magnitude of this general response was strongly dependent on the amount of N added and varied seasonally. These results provide some of the first in situ C and N partitioning estimates for plants growing under the complex web of resource limitations in the boreal understory. PMID- 27197395 TI - Bacterial community response to changes in a tri-trophic cascade during a whole lake fish manipulation. AB - Microbial communities play a key role in biogeochemical processes by degrading organic material and recycling nutrients, but can also be important food sources for upper trophic levels. Trophic cascades might modify microbial communities either directly via grazing or indirectly by inducing changes.in other biotic or in abiotic factors (e.g., nutrients). We studied the effects of a tri-trophic cascade on microbial communities during a whole-lake manipulation in which European perch (Perca fluviatilis) were added to a naturally fishless lake divided experimentally into two basins. We measured environmental parameters (oxygen, temperature, and nutrients) and zooplankton biomass and studied the changes in the bacterial community using next generation sequencing of 16S rRNA genes and cell counting. Introduction of fish reduced the biomass of zooplankton, mainly Daphnia, which partly altered the bacterial community composition and affected the bacterial cell abundances. However, the microbial community composition was mainly governed by stratification patterns and associated vertical oxygen concentration. Slowly growing green sulfur bacteria (Chlorobium) dominated the anoxic water layers together with bacteria of the candidate division ODI. We conclude that alterations in trophic interactions can affect microbial abundance, but that abiotic factors seem to be more significant controls of microbial community composition in sheltered boreal lakes. PMID- 27197396 TI - The energetic contributions of aquatic primary producers to terrestrial food webs in a mid-size river system. AB - Rivers are increasingly recognized as providing nutritional subsidies (i.e., energy and nutrients) to adjacent terrestrial food webs via depredation of aquatic organisms (e.g., emergent aquatic insects, crayfish, fish) by terrestrial consumers. However, because these prey organisms assimilate energy from both aquatic (e.g., benthic algae, phytoplankton, aquatic macrophytes) and terrestrial (e.g., riparian leaf detritus) primary producers, river subsidies to terrestrial consumers represent a combination of aquatically and terrestrially derived energy. To date, the explicit contribution of energy derived from aquatic primary producers to terrestrial consumers has not been fully explored yet might be expected to be quantitatively important to terrestrial food webs. At 12 reaches along a 185-km segment of the sixth-order Scioto River system (Ohio, USA), we quantified the relative contribution of energy derived from aquatic primary producers to a suite of terrestrial riparian consumers that integrate the adjacent landscape across multiple spatial scales through their foraging activities (tetragnathid spiders, rove beetles, adult coenagrionid damselflies, riparian swallows, and raccoons). We used naturally abundant stable isotopes (13C and 15N) of periphyton, phytoplankton, macrophytes, and terrestrial vegetation to evaluate the energetic contribution of aquatic primary producers to terrestrial food webs. Shoreline tetragnathid spiders were most reliant on aquatic primary producers (50%), followed by wider-ranging raccoons (48%), damselflies (44%), and riparian swallows (41%). Of the primary producers, phytoplankton (19%) provisioned the greatest nutritional contribution to terrestrial consumers (considered collectively), followed by periphyton (14%) and macrophytes (11%). Our findings provide empirical evidence that aquatic primary producers of large streams and rivers can be a critical nutritional resource for terrestrial food webs. We also show that aquatically derived nutrition contributes to both shoreline and broader-ranging terrestrial consumers and thus may be an important landscape-scale energetic linkage between rivers and upland habitats. PMID- 27197397 TI - Dynamics of an upland stream fish community over 40 years: trajectories and support for the loose equilibrium concept. AB - Previous theoretical models and empirical studies suggested that communities can exist in a "stochastic" or "loose" equilibrium, diverging transiently but eventually returning toward earlier or average structure, in what we call here the "loose equilibrium concept" (LEC). We sampled the fish communities at 12 local stream reaches spaced broadly throughout a relatively undisturbed watershed in the Ozark Mountains of northern Arkansas, USA, in 11 surveys from 1972 to 2012 at a scale of decades, and at a subset of five of these local sites in a total of 16 surveys, allowing tests of the LEC at different spatial and temporal scales. Multivariate analyses of the dynamics of communities over the 40-year period provided support for the LEC at both "global" and "local" scales within the watershed. At the broadest spatial scale, core species numerically dominated the community, and most common species remained so across all decades. In spite of two extraordinary floods, and interannual variation in abundance of some species, the 12-site and five-site global communities and eight of 12 local communities repeatedly returned toward average positions in multivariate space. Trajectories of the global and local fish communities varied relative to model hypothetical trajectories that were based on gradual vs. saltatory changes, and prevalence of returns toward average community structure. Beta diversity among sites was variable across time, but beta partitioning consistently showed that pure spatial turnover dominated over nestedness, because many common species were consistently distributed either upstream or downstream. This study suggests that vertebrate communities in relatively undisturbed environments may display dynamics consistent with the LEC. The LEC, combined with quantification of community trajectory patterns, can help to clarify whether systems are moving about within ranges of conditions that reflect expected noise, or, conversely, have moved so far out of previous bounds, as a result of climate change or human intervention, that they are permanently changed or "novel." PMID- 27197398 TI - From individuals to population cycles: the role of extrinsic and intrinsic factors in rodent populations. AB - Rodent population cycles have fascinated scientists for a long time. Among various hypotheses, an interaction of an extrinsic factor (predation) with intrinsic factors (e.g., sociality and dispersal) was suggested to lead to the generation of population cycles. Here, we tested this hypothesis with an individual-based model fully parameterized with an exceptionally rich empirical database on vole life histories. We employed a full factorial design that included models with the following factors: predation only, predation and sociality, predation and dispersal, and predation and both sociality and dispersal. A comprehensive set of metrics was used to compare results of these four models with the long-term population dynamics of natural vole populations. Only the full model, which included both intrinsic factors and predation, yielded cycle periods, amplitudes, and autumn population sizes closest to those observed in nature. Our approach allows to model, as emergent properties of individual life histories, the sort of nonlinear density- and phase-dependence that is expected to destabilize population dynamics. We suggest that the individual-based approach is useful for addressing the effects of other mechanisms on rodent populations that operate at finer temporal and spatial scales than have been explored with models so far. PMID- 27197399 TI - Genotypic variation in foundation species generates network structure that may drive community dynamics and evolution. AB - Although genetics in a single species is known to impact whole communities, little is known about how genetic variation influences species interaction networks in complex ecosystems. Here, we examine the interactions in a community of arthropod species on replicated genotypes (clones) of a foundation tree species, Populus angustifolia James (narrowleaf cottonwood), in a long-term, common garden experiment using a bipartite "genotype-species" network perspective. We combine this empirical work with a simulation experiment designed to further investigate how variation among individual tree genotypes can impact network structure. Three findings emerged: (1) the empirical "genotype-species network" exhibited significant network structure with modularity being greater than the highly conservative null model; (2) as would be expected given a modular network structure, the empirical network displayed significant positive arthropod co-occurrence patterns; and (3) furthermore, the simulations of "genotype species" networks displayed variation in network structure, with modularity in particular clearly increasing, as genotypic variation increased. These results support the conclusion that genetic variation in a single species contributes to the structure of ecological interaction networks, which could influence eco ogical dynamics (e.g., assembly and stability) and evolution in a community context. PMID- 27197401 TI - Multi-taxa approach shows consistent shifts in arthropod functional traits along grassland land-use intensity gradient. AB - Intensification of land use reduces biodiversity but may also shift the trait composition of communities. Understanding how land use affects single traits and community trait composition, helps to understand why some species are more affected by land use than others. Trait-based analyses are common for plants, but rare for arthropods. We collected literature-based traits for nearly 1000 insect and spider species to test how land- use intensity (including mowing, fertilization, and grazing) across 124 grasslands in three regions of Germany affects community-weighted mean traits across taxa and in single taxa. We additionally measured morphometric traits for more than 150 Heteroptera species and tested whether the weighted mean morphometric traits change with increasing land-use intensity. Community average body size decreased and community average dispersal ability increased from low to high land-use intensity. Furthermore, the relative abundance of herbivores and of specialists among herbivores decreased and the relative abundance of species using the herb layer increased with increasing land-use intensity. Community-weighted means of the morphometric traits in Heteroptera also changed from low to high land-use intensity toward longer and thinner shapes as well as longer appendices (legs, wings, and antenna). While changes in traits with increasing mowing and fertilization intensity were consistent with the combined land-use intensity, community average traits did often not change or with opposite direction under increasing grazing intensity. We conclude that high land-use intensity acts as an environmental filter selecting for on average smaller, more mobile, and less specialized species across taxa. Although trait collection across multiple arthropod taxa is laborious and needs clear trait definitions, it is essential for understanding the functional consequences of biodiversity loss due to land-use intensification. PMID- 27197400 TI - Multi-trophic consequences of plant genetic variation in sex and growth. AB - There is growing evidence for the influence of plant intraspecific variation on associated multi-trophic communities, but the traits driving such effects are largely unknown. We conducted a field experiment with selected genetic lines of the dioecious shrub Baceharis salicifolia to investigate the effects of plant growth rate (two-fold variation) and gender (males vs. females of the same growth rate) on above- and belowground insect and fungal associates. We documented variation in associate density to test for effects occurring through plant-based habitat quality (controlling for effects of plant size) as well as variation in associate abundance to test for effects occurring through both habitat quality and abundance (including effects of plant size). Whereas the dietary specialist aphid Uroleucon macaolai was unaffected by plant sex and growth rate, the generalist aphid Aphis gossypii and its tending ants (Linepithema humile) had higher abundances and densities on male (vs. female) plants, suggesting males provide greater habitat quality. In contrast, Aphis and ant abundance and density were unaffected by plant growth rate, while Aphis parasitoids were unaffected by either plant sex or growth rate. Arbuscular mycorrhizal fungi had higher abundance and density (both marginally significant) on females (vs. males), suggesting females provide greater habitat quality, but lower abundances (marginally significant) and higher densities on slow- (vs. fast-) growing genotypes, suggesting slow-growing genotypes provided lower resource abundance but greater habitat quality. Overall, plant sex and growth rate effects on associates acted independently (i.e., no interactive effects), and these effects were of a greater magnitude than those coming from other axes of plant genetic variation. These findings thus demonstrate that plant genetic effects on associated communities may be driven by a small number of trait-specific mechanisms. PMID- 27197402 TI - Integrating occupancy models and structural equation models to understand species occurrence. AB - Understanding the drivers of species occrrece s a fundamenal goal in basic and applied ecology. Occupancy models have emerged as a popular approach for inferring species occurrence because they account for problems associated with imperfect detection in field surveys. Current models, however, are limited because they assume covariates are independent (i.e., indirect effects do not occur). Here, we combined structural equation and occupancy models to investigate complex influences on species occurrence while accounting for imperfect detection. These two methods are inherently compatible because they both provide means to make inference on latent or unobserved quantities based on observed data. Our models evaluated the direct and indirect roles of cattle grazing, water chemistry, vegetation, nonnative fishes, and pond permanence on the occurrence of six pond-breeding amphibians, two of which are threatened: the California tiger salamander (Ambysloma californiense) and the California red-legged frog (Rana draytonil). While cattle had strong effects on pond vegetation and water chemistry, their overall effects on amphibian occurrence were small compared to the consistently negative effects of nonnative fish. Fish strongly reduced occurrence probabilities for four of five native amphibians, including both species of conservation concern. These results could help to identify drivers of amphibian declines and to prioritize strategies for amphibian conservation. More generally, this approach facilitates a more mechanistic representation of ideas about the causes of species distributions in space and time. As shown here, occupancy modeling and structural equation modeling are readily combined, and bring rich sets of techniques that may provide unique theoretical and applied insights into basic ecological questions. PMID- 27197403 TI - Positive effects of neighborhood complementarity on tree growth in a Neotropical forest. AB - Numerous grassland experiments have found evidence for a complementarity effect, an increase in productivity with higher plant species richness due to niche partitioning. However, empirical tests of complementarity in natural forests are rare. We conducted a spatially explicit analysis of 518 433 growth records for 274 species from a 50-ha tropical forest plot to test neighborhood complementarity, the idea that a tree grows faster when it is surrounded by more dissimilar neighbors. We found evidence for complementarity: focal tree growth rates increased by 39.8% and 34.2% with a doubling of neighborhood multi-trait dissimilarity and phylogenetic dissimilarity, respectively. Dissimilarity from neighbors in maximum height had the most important effect on tree growth among the six traits examined, and indeed, its effect trended much larger than that of the multitrait dissimilarity index. Neighborhood complementarity effects were strongest for light-demanding species, and decreased in importance with increasing shade tolerance of the focal individuals. Simulations demonstrated that the observed neighborhood complementarities were sufficient to produce positive stand-level biodiversity-productivity relationships. We conclude that neighborhood complementarity is important for productivity in this tropical forest, and that scaling down to individual-level processes can advance our understanding of the mechanisms underlying stand-level biodiversity-productivity relationships. PMID- 27197405 TI - A simple Bayesian method of inferring extinction: comment. PMID- 27197404 TI - Individual and demographic consequences of reduced body condition following repeated exposure to high temperatures. AB - Although the lethal consequences of extreme heat are increasingly reported in the literature, the fitness costs of exposure to sublethal high air temperatures, typically identified in the 30-40 degrees C range, are poorly understood. We examine the effect of high (> or = 35 degrees C) daily maxima on body condition of a semiarid population of White-plumed Honeyeaters, Ptilotula penicillatus, monitored between 1986 and 2012. During this 26-yr period, temperature has risen, on average, by 0.06 degrees C each year at the site, the frequency of days with thermal maxima > or = 35 degrees C has increased and rainfall has declined. Exposure to high temperatures affected body condition of White-plumed Honeyeaters, but only in low-rainfall conditions. There was no effect of a single day of exposure to temperatures > or = 35 degrees C but repeated exposure was associated with reduced body condition: 3.0% reduction in body mass per day of exposure. Rainfall in the previous 30 d ameliorated these effects, with reduced condition evident only in dry conditions. Heat-exposed males with reduced body condition were less likely to be recaptured at the start of the following spring; they presumably died. Heat-exposed females, regardless of body condition, showed lower survival than exposed males, possibly due to their smaller body mass. The higher mortality of females and smaller males exposed to temperatures > or = 35 degrees C may have contributed to the increase in mean body size of this population over 23 years. Annual survival declined across time concomitant with increasing frequency of days > or = 35 degrees C and decreasing rainfall. Our study is one of few to identify a proximate cause of climate change related mortality, and associated long-term demographic consequence. Our results have broad implications for avian communities living in arid and semiarid regions of Australia, and other mid-latitudes regions where daily maximum temperatures already approach physiological limits in regions affected by both decreased precipitation and warming. PMID- 27197406 TI - A simple Bayesian method of inferring extinction: reply. PMID- 27197407 TI - Evidence of soil nutrient availability as the proximate constraint on growth of treeline trees in northwest Alaska: comment. PMID- 27197408 TI - Evidence of soil nutrient availability as the proximate constraint on growth of treeline trees in northwest Alaska: reply. PMID- 27197410 TI - Protestants, Catholics, and Masonic Conspiracies: The British Association in Montreal (1884). AB - The British Association for the Advancement of Science (BAAS), like many nineteenth-century institutions, sought to avoid controversy by excluding the discussion of political and religious topics from its proceedings. Nonpartisanship was a veneer it could hide behind. Yet during the Montreal meeting of 1884-the first time the association ventured beyond the comfortable confines of the British Isles-this "middle way" was tested. While local and visiting Anglophones, many of them BAAS members, viewed the proceedings and character of the association as "decidedly friendly" to religion and as promoting the broad interests of Protestants, Montreal's episcopacy and French-speaking press rallied against the anti-Catholic BAAS, accusing it of harboring a dangerous Masonic clique. In different material and social spaces, the relationship between science, religion, and the association was conceived in distinct ways. In examining this case, this essay seeks to augment the growing body of scholarship within science studies that recognizes the importance of writing both the history and the geography of encounters between science and religion. PMID- 27197409 TI - Fusang: The Enlightenment Story of the Chinese Discovery of America. AB - In 1761 the French scholar and Sinologue Joseph de Guignes announced that "Chinese vessels made the voyage to America many centuries before Christopher Columbus." From the Chinese books in the Bibliotheque du Roi and new missionary reports from Beijing, he concluded that the mythical land of Fusang described by a medieval Buddhist monk could be nowhere other than the west coast of North America, only recently charted by European navigators. Philippe Buache, premier geographe du roi, agreed. At the height of the French Enlightenment, the indigenous geographical tradition of China could be used to further the progress of universal science, providing evidence about issues from the mapping of the Pacific Rim to the organization of the continents. Furthermore, the story of Fusang explained the origins of American peoples, showing that the inhabitants of the New World had arrived there from the Old and contributing to a diffusionist account of the development of civilization in space and time. PMID- 27197411 TI - The Unmaking of a Modern Synthesis: Noam Chomsky, Charles Hockett, and the Politics of Behaviorism, 1955-1965. AB - A familiar story about mid-twentieth-century American psychology tells of the abandonment of behaviorism for cognitive science. Between these two, however, lay a scientific borderland, muddy and much traveled. This essay relocates the origins of the Chomskyan program in linguistics there. Following his introduction of transformational generative grammar, Noam Chomsky (b. 1928) mounted a highly publicized attack on behaviorist psychology. Yet when he first developed that approach to grammar, he was a defender of behaviorism. His antibehaviorism emerged only in the course of what became a systematic repudiation of the work of the Cornell linguist C. F. Hockett (1916-2000). In the name of the positivist Unity of Science movement, Hockett had synthesized an approach to grammar based on statistical communication theory; a behaviorist view of language acquisition in children as a process of association and analogy; and an interest in uncovering the Darwinian origins of language. In criticizing Hockett on grammar, Chomsky came to engage gradually and critically with the whole Hockettian synthesis. Situating Chomsky thus within his own disciplinary matrix suggests lessons for students of disciplinary politics generally and--famously with Chomsky--the place of political discipline within a scientific life. PMID- 27197412 TI - Introduction: Consider the Archive. AB - In recent years, historians of archives have paid increasingly careful attention to the development of state, colonial, religious, and corporate archives in the early modern period, arguing that power (of various kinds) was mediated and extended through material writing practices in and around archives. The history of early modern science, likewise, has tracked the production of scientific knowledge through the inscription and circulation of written records within and between laboratories, libraries, homes, and public spaces, such as coffeehouses and bookshops. This Focus section interrogates these two bodies of scholarship against each other. The contributors ask how archival digitization is transforming historical practice; how awareness of archival histories can help us to reconceptualize our work as historians of science; how an archive's layered purposes, built up over centuries of record keeping, can shape the historical narratives we write; and how scientific knowledge emerging from archives gained authority and authenticity. PMID- 27197413 TI - Scientific Archives in the Age of Digitization. AB - Historians are increasingly working with material that is not only digital but has been digitized. Early digitization projects aimed to encode data for systematic analysis; more recent projects have sought to reproduce unique archival material in a manner that allows for open-ended historical inquiry without the need to travel to archives and manipulate physical objects. Such projects have undeniable benefits for the preservation of documents and access to them. Yet historians must be aware of the scope of digitization, the reasons why material is chosen to be digitized, and limitations on the dissemination of digitized sources. Furthermore, some physical aspects of sources, and of collections of sources, are lost in their digital simulacra. Nonetheless, digitization and the standardization of metadata offer significant possibilities for future archival research and documentation. PMID- 27197414 TI - Archives and the Boundaries of Early Modern Science. AB - This contribution argues that the study of early modern archives suggests a new agenda for historians of early modern science. While in recent years historians of science have begun to direct increased attention toward the collections amassed by figures and institutions traditionally portrayed as proto-scientific, archives proliferated across early modern Europe, emerging as powerful tools for creating knowledge in politics, history, and law as well as natural philosophy, botany, and more. The essay investigates the methods of production, collection, organization, and manipulation used by English statesmen and Crown officers such as Keeper of the State Papers Thomas Wilson and Secretary of State Joseph Williamson to govern their disorderly collections. Their methods, it is shown, were shared with contemporaries seeking to generate and manage other troves of evidence and in fact reflect a complex ecosystem of imitation and exchange across fields of inquiry. These commonalities suggest that historians of science should look beyond the ancestors of modern scientific disciplines to examine how practices of producing knowledge emerged and migrated throughout cultures of learning in Europe and beyond. Creating such a map of knowledge production and exchange, the essay concludes, would provide a renewed and expansive ambition for the field. PMID- 27197415 TI - Finding "Science" in the Archives of the Spanish Monarchy. AB - This essay explores the history of several archives that house the early modern records of Spanish imperial science. The modern "archival turn" urges us to think critically about archives and to recognize in the history of these collections an embedded, often implicit, history that--unless properly recognized, acknowledged, and understood--can distort the histories we are trying to tell. This essay uses a curious episode in the history of science to illustrate how Spanish archives relate to each other and shape the collections they house. During the late eighteenth century a young navy officer, Martin Fernandez de Navarrete, was dispatched to all the principal archives of the Spanish monarchy with a peculiar mission: he was to search for evidence that the Spanish in fact had a scientific tradition. This essay uses his mission to explain how the original purpose of an archive--the archive's telos--may persist as a strong and potentially deterministic force in the work of historians of science. In the case of the archives discussed, this telos was shaped by issues as wide ranging as defending a nation's reputation against claims of colonial neglect and as idiosyncratic as an archivist's selection criteria. PMID- 27197416 TI - The Book and the Archive in the History of Science. AB - In recent years, the history of archives has opened up rich possibilities for understanding early modern science and medicine in material terms. Yet two strands of inquiry, vital to understanding the development of science and medicine as "paper knowledge," have been left largely unpursued: the archiving of personal papers, as distinct from the formation of institutional archives; and the ways in which printed books and archival papers functioned in relation to each other. This essay brings these two strands to the forefront, considering in particular books published posthumously from the notes and correspondence left behind by Nicholas Culpeper, a popular mid-seventeenth-century English vernacular medical author, and John Ray, naturalist and Fellow of the Royal Society. Culpeper's and Ray's cases illustrate, in particular, the central role of women in preserving, circulating, and certifying the authenticity of medical and scientific papers and of any books published posthumously from them. PMID- 27197417 TI - The History of Archives and the History of Science: Comment. AB - Drawing on Terry Cook's famous challenge to the relationship of historians to the archive, this comment responds to the four preceding Focus essays, offering an examination of the roles, in particular, of acquisition and appraisal, canon formation, and place or location in the relationship that historians of science have with the archive. PMID- 27197418 TI - CHARLES COULSTON GILLISPIE (1918-2015). PMID- 27197419 TI - JOAN LISA BROMBERG (1929-2015). PMID- 27197420 TI - TO THE EDITOR. PMID- 27197421 TI - IN REPLY. PMID- 27197424 TI - Paraoxonase-1 activity and pleiotropic properties of simvastatin in obese and non obese patients with stable coronary artery disease (CAD). AB - OBJECTIVES: The study was aimed to assess paraoxonase-1 (PON1) activity, pleiotropic effects of simvastatin, and its relationship to Q192R and M55L polymorphisms in obese and non-obese subjects with stable coronary artery disease (CAD). PATIENTS AND METHODS: The study included 53 subjects (22 obese) aged from 35 to 65 years with CAD. The control group consisted of 53 (18 obese) police officers without CAD. Patients with CAD were treated with simvastatin 40 mg/day for 12 months. The lipid profile, flow mediated dilation (FMD), intima media thickness (IMT), fibrinogen, hs-CRP, TNF-alpha, urine 8-iso-PGF2alpha, and PON1 activity were evaluated in definite time points. PON1 polymorphisms were assessed at baseline in all observed individuals. RESULTS: The patients with CAD and obesity presented at baseline significantly increased hs-CRP level, insignificantly decreased FMD and lower PON1 activity compared to non-obese individuals. There was no association of obesity with 8-iso-PGF2alpha in the CAD and control group. The PON1 activity was significantly higher in 192R carriers in patients and controls, irrespective of obesity. Obesity was not associated with the effects of simvastatin on PON1 activity, urine 8-iso-PGF2alpha, and TNF alpha, whereas it blunted its effect on the FMD improvement. The Q192R polymorphism was associated with simvastatin effectiveness on hs-CRP and FMD. CONCLUSION: Obesity and Q192R PON1 polymorphism are significantly associated with pleiotropic effects of simvastatin therapy in patients with stable CAD. PMID- 27197423 TI - PTTG and Ki-67 expression in pituitary adenomas. AB - INTRODUCTION: The unpredictable biology of pituitary adenomas makes it a therapeutic challenge. Moreover ,histopathology of pituitary carcinomas and locally invasive adenomas are indistinguishable from benign tumors and a new marker which would enable to differentiate those lesions is vital. The aim of the study was to evaluate Ki-67 and PTTG (pituitary tumour--transforming gene) expression in pituitary adenomas and their applicationas markers of tumour aggressiveness. MATERIAL AND METHODS: A retrospective analysis of 55 patients: 32 females(58%) and 23 males (42%), mean age 50 +/- 16 years who underwent pituitary tumor surgery between 2003-2012. Ki-67 and PTTG indices were determined by immunohistochemical staining. Magnetic resonance imaging or computed tomography was performed beforehand and one year after surgery to figure a potential tumour progression, tumour size and correlation to adjacent tissues. RESULTS: The expression of Ki-67and PTTG was revealed in cell nucleiin 88% and 85% of adenomas, respectively. The median Ki-67 and PTTG indices were 1.4 and 1.0, respectively(p = 0.006). In the group with macroadenoma as compared with the group with microadenoma, median Ki-67 index was higher (1.4% vs. 1.03%; p = 0.02). We did not find correlation between both Ki-67 and PTTG indices and tumour progression. Tumours with positive immunostaining towards FSH revealed lower Ki 67 and PTTG indices than the rest with a negative one (0.6% vs.1.84%, p = 0.0004 and 0.67% vs 1.23%,p = 0.047; respectively). However, PTTG index was higher in the group with acromegaly as compared to the group with clinically non functioning pituitary adenoma (NFPA) (1.28% vs.0.35%; p = 0.02). CONCLUSIONS: Positive nuclear expression of Ki-67 and PTTG was observed in the majority of pituitary adenomas. Only higher Ki-67 expression was related to the tumour invasiveness found on MRI/CT. Tumour progressionwas not related to both Ki-67 and PTTG expression. PMID- 27197425 TI - Validation of the Polish version of the EORTC Head and Neck module (QLQ-H&N35). AB - AIM: The aim of this study was to psychometrically validate the EORTC translated, Polish version of the EORTC QLQ-H&N35 questionnaire to support using it in the Polish clinical setting in patients with head and neck malignancies. MATERIALS AND METHODS: Patients with histologically confirmed head and neck malignancies were included in the study. All patients filled in the Polish version of the EORTC QLQ-C30, the EORTC QLQ-H&N35 module, and a demographic questionnaire. Standardized validity and reliability analyses were performed. RESULTS: During the recruitment period a total of 176 patients (82 females - 46.6%) were enrolled into the study, with a mean age of 54.3 +/- 11.2 years. Cronbach alpha values ranged from 0.71 to 0.87. Satisfactory convergent and discriminant validity in multi-trait scaling analyses was seen. CONCLUSIONS: The Polish version of the EORTC QLQ-H&N35 module is a reliable and valid tool for measuring HRQoL in Polish patients with head and neck malignancies. It can be fully recommended for use in the Polish clinical setting. PMID- 27197426 TI - The effect of exercise on the secretion of B-type natriuretic peptide in the groups of patients with diabetes and myocardial infarction with preserved left ventricular systolic function. AB - OBJECTIVE: 1. Evaluation of the impact of physical exercise on the secretion of type B natriuretic peptide (BNP) in patients with preserved left ventricular function, in the group after myocardial infarction and in the group with diabetes. 2. Evaluation of the effect of hemodynamic parameters and exercise tolerance on BNP secretion in the study groups. 3. Comparison of echocardiographic image, biochemical changes and exercise tolerance in both groups. MATERIAL AND METHODS: The study included patients with type 2 diabetes without a history of myocardial infarction and patients after myocardial infarction treated with primary angioplasty, with preserved left ventricular systolic function (LV EF >= 40%). The study included 99 patients, aged 40-75. Patients had an echocardiographic test performed for systolic and diastolic left ventricle function evaluation, an electrocardiographic exercise test and blood collection for BNP determination before and immediately after the exercise test. RESULTS: The increase of BNP release after exercise was observed in both groups: in the group with a history of myocardial infarction, the BNP increase was 37.8 +/- 45.9 pg/ml, whereas in the group with diabetes 18.1 +/- 26.8 pg/ml. BNP after exercise and increase in BNP during exercise was significantly higher in subjects with a history of myocardial infarction (p = 0.008). There was no association between exercise-induced increase in BNP and the duration of exercise or exercise tolerance. Exercise tolerance was higher in subjects with a history of myocardial infarction, but the difference did not reach a statistical significance (METS 8.7 +/- 3.3 vs 7.92 +/- 2.3; p = 0.08). CONCLUSIONS: 1. During the exercise test an increase in BNP secretion was observed in subjects with diabetes and with the history of myocardial infarction, with preserved LV systolic function. 2. BNP growth during exercise test was significantly higher in patients after myocardial infarction. 3. The exercise-induced BNP growth did not significantly correlate with exercise duration or exercise tolerance measured with the metabolic equivalent - METS. PMID- 27197427 TI - [Risk factors of death occurrence in patients with acute kidney injury in the course of severe cardio-vascular complications]. AB - INTRODUCTION: Acute kidney injury (AKI) is a frequent and serious complication in patients with cardiovascular disease. The aim of the study was to evaluate the risk of death in patients with AKI complicating severe cardiovascular diseases. MATERIAL AND METHODS: A retrospective analysis of 246 patients surveys (157 men and 89 women aged 67.9 +/- 14.8 years) with AKI in the course of severe cardiovascular diseases, hospitalized in intensive care units and words of nephrological profile in years 2000-2011 were performed. RESULTS: The majority of patients (95.9%) with AKI required hemodialysis treatment. The mortality rate in the study group was high and amounted to 69.5% and the recovery of renal function was observed in 39 patients (27.3%). Kidney disease before the onset of AKI was observed in 116 patients (47.2%). Patients with arterial hypertension have more frequently oligoanuria (p = 0.001), needs more hemodialysis sessions (p = 0.029) and stay longer in hospital (p = 0.012). In multivariate analysis, the occurrence of death depend on such factors as: the lack of recovery of renal function, bleeding from gastrointestinal tract, urinary tract infections, and other infectious and noninfectious complications. CONCLUSIONS: No recovery of renal function and comorbidity while AKI in the course of severe cardiovascular diseases increase the risk of death. PMID- 27197428 TI - [Evaluation of influence of Dupuytryen contracture's operative treatment on increase of quality of hand's function basing on research in use PEM (Patient Evaluation Measure) questionnaire]. AB - INTRODUCTION: Dupuytren's contracture is a progressive fibrosis of facial structures of the palmar surface of the hand, gradually leading to a reduction of its functions by impaired range of motion of fingers. MATERIALS AND METHODS: Clinical material consisted of 95 patients treated surgically in the Second Department of Surgery of the Jagiellonian University in 2006 - 2011 because of Dupuytren's contracture. Based on a study using PEM questionnaire (Patient Evaluation Measure) an assessment of the quality of life before and after surgery was made. RESULTS: The average numeric value obtained in the PEM questionnaire before surgery was 30 points (SD +/- 14.35). The postoperative controls were found of gradual decrease in the value and so after three months it was 22.39 points (SD +/- 14.23), and after a year it reached the value of 18.12 points (SD +/- 12.43). Statistically significant correlations (p < 0.001) were demonstrated between test results of PEM taken before and after 3 and 12 months after surgery. CONCLUSIONS: It has been shown that Dupuytren's contracture has negative impact on quality of life but the quality of life improves after surgical treatment. PMID- 27197429 TI - [Urinalysis in patients at the early stage of acute pancreatitis]. AB - Urinalysis is a routine and cheap laboratory test that provides clinically useful information in patients with acute abdominal conditions, including acute pancreatitis. The aim of the study was to assess the relationships between the results of urinalysis and the course of the disease among 65 patients with acute pancreatitis (34 men and 31 women, mean age 61 +/- 19 years) at the early phase of the disease, i.e. during the first 72 hours from the onset of symptoms. Mild acute pancreatitis was diagnosed in 47 patients, moderately severe in 13 and severe in 5. The most prevalent abnormalities were proteinuria (43% of patients), high urinary bilirubin (20%), erythrocytes (18%), glucose (18%) and leukocytes (17%). High urinary protein and low specific gravity were associated with more severe acute disease and with acute kidney injury. The severity of bilirubinuria and proteinuria were positively correlated with urine concentrations of neutrophil gelatinase associated lipocalin (NGAL). Urinalysis should be routinely performed in patients with acute pancreatitis. PMID- 27197430 TI - [Induced sputum supernatant prostaglandin E2 during oral aspirin challenge of asthmatic patients with and without aspirin hypersensitivity and healthy controls -pilot study]. AB - The aim of this pilot study was to evaluate changes in the concentration of prostaglandin E2 (PGE2) in induced sputum supernatant in 3 groups: sub- jects with NSAID-exacerbated respira- tory disease (NERD), aspirin tolerant asthma (ATA) and healthy controls (HC), before and after oral aspirin chal- lenge test. The study was conducted in the years 2014-2015 at the Clinical Department of the Pulmonology Clinic at the University Hospital in Cracow. 43 patients were enrolled in the study (NERD - n = 15, ATA - n = 15 and HC - n = 13). All of them underwent a placebo-controlled oral aspirin challenge. Sputum was induced 24 hours before the challenge and immediately after the test. Induced sputum was processed in order to obtain cystospin slides to depict inflammatory cell patterns and supernatants, in which PGE2 was measured. The concentration of PGE2 was determined using mass spectrometry coupled with gas chromatography (gas chromatography/mass spectrometry - GC/MS). After aspirin challenge, the concentration of PGE2 in induced sputum supernatant decreased in both asthmatics hypersensitive to aspirin (p = 0.01) and those who tolerated aspirin well (p = 0.17). The change in the healthy control group was not statistically significant. These results support the cyclooxygenase theory of PGE2 inhibition by aspirin. However, the mechanism of bronchoconstriction after aspirin administration alone in patients with NSAID-exacerbated respiratory disease remains unclear. PMID- 27197431 TI - [Others physical methods in psychiatric treatment based on electromagnetic stimulation]. AB - In the last decades a few new physical methods based on the electromagnetic head stimulation were subjected to the clinical research. To them belong:--vagus nerve stimulation (VNS),--magnetic seizure therapy/magnetoconvulsive therapy (MST/MCT), -deep stimulation of the brain (DBS) and--transcranial direct current stimulation (tDCS). The paper presents a description of mentioned techniques (nature, advantages, defects, restrictions), which were compared to the applied electroconvulsive treatment ECT, earlier described transcranial magnetic stimulation TMS and the pharmacotherapy (the basis of the psychiatric treatment). PMID- 27197432 TI - [Coronary artery disease as cause of non-odontogenic toothache. A review of literature]. AB - AIMS: The aim of the work is to present, based on the latest available literature, the clinical picture of non-odontogenic toothache as a symptom of coronary artery disease. MATERIAL AND METHODS: Analysis of full text scientific studies, including research and casuistic works, which present the characteristics of the most frequently reported pain symptoms of the viscerocranium area, including toothache, in patients in the course of coronary artery disease. RESULTS: The pain of the viscerocranium region turned out to be the most frequent symptom of ischaemic heart disease when chest pain is absent. The most frequently reported pain symptoms of the viscerocranium area in the course of ischaemic heart disease involve: pain of the upper part of the thorax, left side of the mandible, right side of the mandible, the region of the left temporomandibular joint and the left ear, toothache. The patients most frequently described the pain as pressing and burning. The pain also intensified during physical exercise. CONCLUSION: The aetiology of toothache may be very diverse. An accurate and quick differential diagnosis of odontogenic and non-odontogenic toothache is not an easy task even for an expert clinician. Nonetheless, it is crucial for patients' life and health. A dentist may play a significant role in an early diagnosis of ischaemic heart disease. PMID- 27197433 TI - [Kartagener syndrome--case report]. AB - INTRODUCTION: Kartagener syndrome is a very rare, congenital, cilia-related disease comprising a triad of bronchiectasis, sinusitis and situs inversus. It is diagnosed in about 50% patients with primary ciliary dyskinesia (PCD). CASE REPORT: The authors report a case of a 72-year old female patient with a history of chronic cough and expectoration of muco-purulent secretion. An X-Ray examination in Posterior-Anterior projection revealed an abnormal configuration of chest's organs. Diagnosis was complemented with Computed Tomography (CT) of chest and paranasal sinuses and laboratory tests as well. Compilation of clinical symptoms and test results led to the diagnosis of Kartagener syndrome. CONCLUSION: This case report shows the usefulness of diagnostic imaging in the diagnostic process of Kartagener syndrome, as well as during subsequent monitoring of the disease. PMID- 27197434 TI - [In the 100 birth anniversary of the pioneer of stereotactic brain surgery in Poland professor Oskar Liszka. Functional neurosurgery in Poland and in Krakow]. AB - This article is the report from the meeting of the Medical Society of Cracow, that has been devoted to the 100 birth anniversary of Oskar Liszka, Assoc. Prof., MD. In the course of the meeting Professor Oskar Liszka's figure has been reminded and his work as a pioneer of stereotactic surgery in Poland has been discussed. In the next two sections, the development of functional neurosurgery in Poland and achievements in this field in the Department of Neurosurgery and Neurotraumatology of Jagiellonian University Collegium Medicum in Krakow have been presented. PMID- 27197435 TI - [An Epidemiological Study on an Influenza Outbreak at Day Nurseries and Nursing Institutions in Gunma]. AB - OBJECTIVE: The features of influenza outbreaks (IOs) at day nurseries (DN), facilities for the handicapped (FH), and care homes for the elderly (CHE) are unclear. The aim of this study was to clarify these features at each institution. MATERIALS AND METHODS: The authors examined IOs (n = 258) that occurred at DN, FH, or CHE in Gunma Prefecture between 2012 and 2014, and the characteristics of such IOs were investigated epidemiologically. Results : (1) DN had a higher number of users, a higher user-to-staff member ratio, and a lower number of staff members compared to those at FH. and CHE. (2) The rate of IOs was highest at DN. (3) At DN and CHE, the occurrence of IOs during the early period of the influenza season in the community was higher than that during the late period of the influenza season in the community. (4) IOs persisted for longer at DN. (5) The IOs attack rates were highest at FH during the early, late, and total periods, although those at FH and CHE decreased slightly during the late period. (6) The attack rates of staff members at CHE during the early period and at FH during the late period were high. The attack rate of staff members at CHE significantly decreased during the late period. CONCLUSIONS: The occurrence of IOs at DN and CHE will be influenced by influenza epidemicity seen outside of the institutions. IOs often occurred and were prolonged at DN, which can be explained by the high rate and frequency of secondary infection resulting from the very close contact among users. At CHE, the attack rate increased due to the very close contact between users and staff members, especially during the early period; however, the attack rate at CHE during the late period decreased due to the prevention of secondary infection. At FH, the attack rates were higher compared to those at DN and FH, which was influenced by the high degree of contact among users and between users and staff members. The spread and prolongation of IOs will be influenced by the users',high degree of behavior, the high degree of contact between users, and the high degree of contact among users and between users and staff members. Prevention of IOs and their prolongation and spread should be conducted according to factors that affect the duration and spread of IOs, as described above. PMID- 27197436 TI - [Epidemiological Survey of the Extended-spectrum beta-lactamase-producing Bacteria in Hospitals and Nursing Homes in Morioka Secondary Medical Area Zone of Iwate Prefecture]. AB - The spread of ESBL-producing bacteria (ESBLs) in local communities is a crucially important issue related to infection control. We investigated the relevance of isolation of ESBLs and the risk factors influencing the isolation rates of these organisms at medical facilities (4 rural hospitals, A-D; 4 nursing homes, a-d) located in the Morioka medical area. The isolation rates of ESBLs at 4 hospitals were estimated from the patient medical records from April 2013 to March 2014. Also, ESBLs were isolated from stool samples from residents in 4 nursing homes during almost the same period, and were analyzed to ascertain their genotypes. Furthermore, we compared the isolation rates of ESBLs among four hospitals to determine the influence of use of third-generation cephalosporins and alcohol based hand rubs, and also among four nursing homes to identify the clinical backgrounds of the nursing home residents influencing the isolation rates. The isolation rates of ESBLs in hospitals and nursing homes were 13.3% (3.6-25.0%) and 9.3% (3.4-21.0%), respectively. Hospital B, which had the highest isolation rate of ESBLs, showed the highest rate of use of third-generation cephalosporins. On the other hand, Hospital A, with a lower isolation rate of ESBLs, showed the highest frequency of use of alcohol rubs. The rate of use of enteral nutrition was significantly higher in the nursing homes with higher isolation rate of ESBLs than those with lower isolation rates (odds ratio 2.71, p < 0.05). Nursing home c, with a significantly higher isolation rate of ESBLs, showed higher usage of adult diapers as well as higher rates of residents with recent hospitalization and high-level care. All ESBLs (13 Escherichia coli) isolated from nursing home c showed the same genotype: CTX-M-3. Although numerous ESBLs were isolated from the hospitals and nursing homes investigated in this study, the isolation rates of ESBLs and the clinical backgrounds of the patients differed greatly among the medical facilities in the same area. Furthermore, as patients and residents were transferred reciprocally among the hospitals and nursing homes, it was suggested that infection control for ESBLs at any individual facility alone was not sufficient and also that cooperative education and information sharing on ESBLs among facilities in the same area might be important. PMID- 27197437 TI - [The Abdominal Ultrasonographic Appearance of Acute Phlegmonous Gastritis]. AB - Phlegmonous gastritis (PG) is a nonspecific suppurative inflammation disease arising from the submucosal layer, and extending to the full thickness of the stomach. We herein report on a case of acute PG which was diagnosed with abdominal ultrasonography. A 64-year-old man presented at a hospital after having recently undergone pacemaker implantation for the treatment of complete atrioventricular block. He was admitted as an emergency due to a fever of 39 degrees C. He showed anorexia, epigastralgia, vomiting of coffee-ground emesis on the second hospital day, and abdominal ultrasonography (AUS) performed on the third hospital day showed the disappearance of the normal laminated structure and hypoechoic thickening of the stomach walls. Upper gastrointestinal endoscopy revealed significant hyperplasia of the stomach walls, an erythrogenic mucosa, and poor extension. On the fourth hospital day, computed tomography revealed concentric thickening of the stomach walls. Streptococcus pyogenes was cultured from his blood sample. Based on those findings, the patient was diagnosed as having acute phlegmonous gastritis. His clinical symptoms improved and the abnormal ultrasonographic examination findings thereafter returned to normal following the administration of antibiotics. PG should therefore be included in the differential diagnosis when encountering patients with acute abdomen. We experienced a rare case of acute phlegmonous gastritis and AUS was useful for making an early diagnosis. PMID- 27197438 TI - [Severe Japanese Spotted Fever Complicated by Acute Respiratory Failure in Kobe City]. AB - We report herein on a case of severe Japanese spotted fever complicated by acute respiratory failure in Kobe City. A 70-year-old female presenting with general malaise and systematic erythema was admitted to our hospital in June, 2013. From her history and physical examination, she was found to be suffering from scleroderma and mild interstitial pneumonia. From admission, the patient was noted to have a fever of 39 degrees C accompanied by relative bradycardia. Physical examination revealed a black eschar on her right leg, making us suspect rickettsial infection since Kobe City is not an area predisposed to Japanese spotted fever. Three days after admission, her condition worsened and treatment with minocycline and levofloxacin was initiated in accordance with the treatment protocol for Japanese spotted fever. The following day, the patient developed acute respiratory distress syndrome (ARDS) and was put on a respirator. She gradually recovered with the antibiotic treatment and was discharged from the hospital 23 days after admission. The diagnosis of Japanese spotted fever was confirmed by conducting a polymerase chain reaction test on the eschar. Japanese spotted fever is noted to occur in any place other than Kobe City. Late diagnoses may result in aggravated cases of Japanese spotted fever, with the possibility of developing ARDS as a complication. PMID- 27197439 TI - [Unexpected Diseases in Two Patients with False-Positive Dengue Immunoglobulin M Antibody Test Results]. AB - In 2014, an outbreak of 162 domestic dengue fever infections occurred in Tokyo, Japan; the first outbreak of its kind in 70 years. Nineteen of these cases were confirmed in our center. Advancements in diagnostic methods have enabled an earlier diagnosis of dengue fever; however, unfamiliarity with the clinical course and characteristics of diagnostic tests for dengue fever can lead to misdiagnosis. We herein describe 2 cases of Japanese patients with false-positive dengue immunoglobulin M antibody test results, who were finally diagnosed as having dermatomyositis and acute hepatitis A infection, respectively. PMID- 27197440 TI - [A Case of Bacteremia Caused by Ochrobacterium intermedium]. AB - We report herein on a case of bacteremia caused by Ochrobactrum intermedium (O. intermedium) identified with biotyper matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS). An 86-year-old man was admitted to our hospital with paralysis of the right side of the body and dysphagia. He was diagnosed as having a pontine infarction based on the brain MRI findings and was admitted to hospital to have anti-platelet therapy. Three days after admission, he had a fever. Although he had redness and swelling at the peripheral venous catheter insertion site, he was diagnosed as having aspiration pneumonia, since he had fine crackles on auscultation. Soon after taking two sets of blood cultures and removal of the peripheral venous catheter, sulbactam/ampicillin (SBT/ABPC) was administrated. Fifty three hours after incubation, gram-negative bacilli was detected from an aerobic bottle and identified as O. intermedium with MALDI-TOF MS (Bruker MS). Antimicrobial chemotherapy was changed to meropenem (MEPM). He was treated for a total of seven days, and recovered without relapse. Infection caused by O. intermedium has been very uncommon, however, O. intermedium has been recognized as an emerging pathogen in immunodeficient and immunocompetent patients. Since identification of Ochrobactrum species by biochemical methods could be difficult, MALDI-TOF MS might be helpful to clarify Ochrobactrum species just as in the present case. PMID- 27197441 TI - [Acute Pyelonephritis and Candidemia Due to Candida lusitaniae: A Case Report]. AB - Although candiduria is becoming increasingly common among hospitalized patients, Candida lusitaniae is a rare pathogen that account for less than 1% of Candida species isolated from urine. Ascending pyelonephritis and candidemia due to Candida species are uncommon complications. We report herein on a case of acute pyelonephritis and candidemia due to C. lusitaniae. A 66-year-old man presented with a high fever during hospitalization at our hospital following septic shock due to ischial osteomyelitis treated with tazobactam/piperacillin for 29 days. We suspected acute pyelonephritis, and urinary Gram staining showed only yeasts and leucocytes. The next day, blood culture and urine culture tested positive and showed yeast-like fungi. We diagnosed acute pyelonephritis and candidemia due to Candida species and started treatment with fluconazole. C. lusitaniae was identified on the hospital day 34 and treated with fluconazole for 14 days. Candida albicans was the most prevalent species isolated from the urinary tract, however non-albicans Candida species have emerged and are now dominant because of the advent and increasing use of fluconazole. C. lusitaniae is a rare but important pathogen, that is generally susceptible to fluconazole and resistant to amphotericin B. It is necessary to choose an appropriately effective antifungal drug based on identification of the fungal species. PMID- 27197442 TI - [A Case of Brucellosis with Intermittent Fever in a Patient Returning from France]. AB - We herein report on a 62-year-old man who presented with symptoms of intermittent fever that persisted after returning from a trip to France. During his trip, he had eaten natural cheese. Although no bacteria could be isolated from blood culture, the serum agglutination test showed a positive antibody titer of 1 : 160 for Brucella canis. The patient responded well to combination antibiotic therapy consisting of gentamicin, rifampicin, and doxycycline, and his symptoms improved. He became antibody-negative after antibiotic therapy. Although the present case may have been a case of B. canis infection, considering the epidemiology of brucellosis in France, serological cross-reactivity with Brucella melitensis infection is also a possibility. Concerns regarding the reemergence of brucellosis have recently been reported in France, and most cases are caused by B. melitensis. Clinicians should be aware of the fact that blood cultures must be incubated for >= 21 days for isolation of Brucella and that in Japan, antibody measurement of B. melitensis cannot be performed on a commercial basis. PMID- 27197444 TI - [Surgical procedures of Meniere disease]. PMID- 27197443 TI - [Precise medicine of hereditary hearing loss]. PMID- 27197446 TI - [Efficacy comparison between endolymphatic sac surgery and semicircular canal occlusion in the treatment of stage 4 Meniere disease]. AB - OBJECTIVE: To compare the vertigo controlling situation between the endolymphatic sac decompression(ELSD) and semicircular canal occlusion (SCO) in stage 4 Meniere disease. METHOD: Fourteen patients who underwent endolymphatic sac decompression and 9 patients who underwent semicircular canal occlusion from 2009 to 2013 were followed. All patients has complete preoperative examination and postoperative follow-up. RESULT: The vetigo control of the patients underwent endolymphatic sac decompression: completely control 35.7%; basic control 28.6%; partly control 14.3%; the vetigo control of the patients underwent semicircular canal occlusion: completely control 88.9%; basic control 11.1%. CONCLUSION: ELSD and SCO are alternative methods for the patients of stage 4. SCO has a much highter complete vertigo control rate. For the patients without practical listening, SCO is a better choice. PMID- 27197445 TI - [Difference of cervical vestibular evoked myogenic potentials in different audition stage of Meniere disease]. AB - OBJECTIVE: Our goal was to find whether inreversible function damage of saccule was exist and correlated in Meniere's patients with different audition. METHOD: Senenty-nine patients with unilateral Meniere's disease, who visited the Dizziness Diagnosis and Treatment Centre of the Second Military Medical University from January to July in 2015 were included. They were grouped as slightly audition damage group (41 cases), mildly-severely audition damage group(38 cases). Meanwhile 20 normal controls underwent the research. The cervical vestibular evoked myogenic potentials were conducted in symptom free period. RESULT: There was no significant difference of the C-VEMP inducing rate between slightly audition damage group and normal control group. While a statistically difference showed between mildly-severely audition damage group and normal control group or slightly audition damage group. P1, N1 latency had no statistically difference between three groups. The P1-N1 amplitude and asymmetric ratio had no difference between slightly audition damage group and normal control group, but had a statistically difference between mildly-severely audition damage group and slightly audition damage group, normal control group. CONCLUSION: The function of saccule in Meniere's patients decreased with the aggravation of audition damage. PMID- 27197447 TI - [Comparison of caloric responses between vestibular migraine and Meniere disease patients]. AB - OBJECTIVE: To compare the features of caloric tests in vestibular migraine (VM) and Meniere's disease (MD) patients, and provide objective evidence for differentiating the 2 groups of patients. METHOD: This case-control study included 11 MD patients with left ear involved and mild to moderate impaired hearing, and 18 matched cases with VM. All participants received caloric tests. Maximum slow phase velocities (SPVmax) were used to describe horizontal and vertical nystagmus respectively and were compared between the 2 groups. Horizontal and vertical canal parasis(CP) were calculated according to respective SPVmax. Unilateral (UW-VR) or bilateral (BW-VR) weakness of vestibular response, and positive unilateral (UVR) or bilateral (BVR) vertical response or negative bilateral vertical response (NBVR) were judged by the boundary point of SPVmax of 5 degrees /s respectively. Total left (LV) or right (RV) Vertical reactions were calculated accoeding to vertical SPVmax,and inter ears difference of vertical responses (IED-VR) calculated from LV minus RV. RESULT: There were no significant differences in age and gender between the 2 groups. Horizontal SPVmax of all of caloric tests of VM group,except the left cold (LC), were statistically larger than that of MD group (P < 0.05) and the maximum responses of right warm (RW) caloric test in VM group (34.50 +/- 17.77) were significantly greater than that in MD group (12.82 +/- 6.69) (P < 0.01). Only the vertical SPVmax of RW of all caloric tests has statistically difference between the 2 groups (P < 0.01), and the maximum responses of RW caloric test in VM group (6.00 +/- 4.45) were significantly stronger than that of LC in MD group (1.27 +/- 2.00) (P < 0.01). Horizontal CP >= 25% of the 2 groups(VM: 72.22%, MD: 54.55%) were not statistically different, while the proportions of UW-VR and BW-VR in VM group (5.56%, 0) were significantly lower than that in MD group (27.27%, 18.18%) (P < 0.05). Vertical CP >= 25% of the 2 groups (VM: 94.44%, MD: 27.27%) were significantly different (P < 0.01), and the proportions of positive UVR (left: 5.56%, right: 77.78%) and BVR (0) and NBVR (16.67%) in VM group were significantly different from that in MD group (UVR (left: 9.09%, right: 0), BVR (0), NBVR (90.91%)) (P < 0.01). There was statistically difference between LV and RV in VM group (P < 0.01, LV < RV), while no difference were showed in MD group. IED-VR in VM group (left intenser: 16.67%, right intenser: 83.33%) was statistically different from that in MD group (left intenser: 36.36%, right intenser: 9.09%, both no difference: 54.55%) (P < 0.01). CONCLUSION: Vestibular responses of caloric test are more sensitive, and vertical reactions are more easily induced in VM patients than in MD. Caloric test can be used to differentiate the 2 groups of diseases. PMID- 27197448 TI - [The false-negative reasons of positioning test in benign paroxysmal positional vertigo]. AB - OBJECTIVE: To analyze the false-negative proportion and reasons of positioning test in benign paroxysmal positional vertigo (BPPV). METHOD: Sixty-eight cases were reviewed and analyzed during February to April 2009. All patients had typical clinical history of BPPV and diagnosed by positioning test,and all were treated with PRM successfully. If positioning test at the first time were negative, examinations repeated after either head shaking or return visits. RESULT: Thirteen patients (19.12%) appeared false-negative in positoning test, and 11 cases showed typical nystagmus after head shaking,while 2 cases were diagnosed by return visitis the next day. There were no statistically difference between false-negative group and positive group in age (P > 0.05), gender (P > 0.05), course of disease (P > 0.05) and types of semi-circular canal (P > 0.05). CONCLUSION: Re-examinations after head shaking or return visits are useful for the diagnosis in the suspected BPPV patients who have negative positioning test. PMID- 27197449 TI - [Analysis of relation between the development of study and literatures about benign positional paroxysmal vertigo published international and domestic]. AB - OBJECTIVE: Benign paroxysmal positional vertigo (BPPV) is a common vestibular disorder that causes vertigo. Study of BPPV has dramatically rapid progress in recent years. We analyze the BPPV growth METHOD: We searched the international data quantity year by year in database of PubMed, ScienceDirect and WILEY before 2014 respectively, then we searched the domestic data quantity year by year in database of CNKI, VIP and Wanfang Data before 2015 by selecting "Benign paroxysmal positional vertigo" as the keywords. Then we carried out regression analysis with the gathered results in above databases to determine data growth regularity and main factors that affect future development of BPPV. Also, we analyzes published BPPV papers in domestic and international journals. RESULT: PubMed database contains 808 literatures, ScienceDirect contains 177 database and WILEY contains 46 literatures, All together we collected 1 038 international articles. CNKI contains 440 literatures, VIP contains 580 literatures and WanFang data contains 449 literatures. All together we collected 1 469 domestic literatures. It shows the rising trend of the literature accumulation amount of BPPV. The scattered point diagram of BPPV shows an exponential growing trend, which was growing slowly in the early time but rapidly in recent years. CONCLUSION: It shows that the development of BPPV has three stages from international arical: exploration period (before 1985), breakthrough period (1986 1998). The deepening stage (after 1998), Chinese literature also has three stages from domestic BPPV precess. Blank period (before the year of 1982), the enlightenment period (1982-2004), the deepening stage (after the year of 2004). In the pregress of BPPV, many outsantding sccholars played an important role in domestic scitifction of researching, which has produced a certain influence in the worldwide. PMID- 27197450 TI - [Analysis and evaluation of the balance function in patients with type 2 diabetes]. AB - OBJECTIVE: Evaluation and analyze the characteristics of balance function in patients with type 2 diabetes, and to find out the importance of proprioception, vision and vestibular in postural control. METHOD: All subjects were divided into two groups, 37 normal individuals, 33 patients with type 2 diabetes mellitus. All were assessed by computerized posturography under six upright stance.conditions: including standing on the firm surface and foam with eyes open and closed. RESULT: (1) On anteroposterior,the scores of proprioception, vision and vestibular were 93.96 +/- 7.95, 80.22 +/- 16.24, 70.87 +/- 20.99, the normal were 98.00 +/- 2.18, 91.44 +/- 6.01, 80.44 +/- 7.81. There were significances between diabetes mellitus group and normal control group (P < 0.05) respectively. (2) On lateral, the scores of vision and vestibular were 80.39 +/- 12.60, 73.96 +/- 16.04, and the normal were 92.11 +/- 4.50, 83.18 +/- 9.45. There were significances with P < 0.05 between diabetes mellitus group and normal control group. However, there was no obvious difference in proprioception scores between the two groups. (3) The limit of stability of normal group were (176.47 +/- 44.13) mm2; diabetic group was (143.13 +/- 62.30) mm2. There was statistical significance between the group with P < 0.05. (In diabetic patients, there was no significant difference between the no dizziness group and the dizziness group of the scores of proprioceptive, visual, vestibular as well as stable limits, P > 0.05. CONCLUSION: The balance function of patients with type 2 diabetes decreased. It is the main characteristic that the vision and vestibular decreased more significantly in the postural control. PMID- 27197451 TI - [Effects of IAA/HRP on the proliferation and apoptosis of SACC-83 cells]. AB - OBJECTIVE: To study the effect of IAA/HRP on the proliferation and apoptosis of human SACC-83 cells in vitro,and its molecular mechanism. METHOD: The rate of proliferation inhibition was determined by CCK-8 assay, the apoptosis-related gene Caspase-3 and Livinalpha mRNA and protein expression levels were measured by real-time PCR and Western blot. RESULT: IAA/HRP could inhibit proliferation of SACC-83, which depending on the time and dosage (P < 0.05); can-up-regulate the Caspase-3 mRNA and protein expression levels and reduction of the mRNA and protein of the Livina expression, (both P < 0.05). CONCLUSION: IAA/HRP can inhibit the proliferation and induce the apoptosis of SACC-83 cells, which may due to its regulation of the expression of Caspase-3 and Livinalpha mRNA expression. PMID- 27197452 TI - [Application of the anxiety and depression scale of patients with nasal septum deviation]. AB - OBJECTIVE: To evaluate the anxiety and depression status of patients with nasal septum deviation before and after surgery, and explore the relationship between anxiety and depression and nasal symptoms. METHOD: By means of visual analogue scale (VAS) as the evaluation index of quality of life, self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were used to analyze statuses before and after surgery. The 98 patients with nasal septum deviation were collected. RESULT: The preoperative SAS/SDS scores of the nasal septum deviation patients were higher than those of the national standards. The level of anxiety and depression were lower than the national norm after treatment. The patients of the normal and moderate SAS/SDS scores felt better after surgery. The patients of the severe SAS/SDS scores felt the symptoms improve poor. CONCLUSION: Doctors should pay attention to the application of the SAS/SDS in patients of nasal septum deviation. Surgeon should actively communicate with severe patients in psychological problems, and strictly control the surgical indication of such patients. PMID- 27197453 TI - [The application value of parathyroid hormone level in predicting post-operative hypocalcemia after total thyroidectomy]. AB - OBJECTIVE: To investigate the application value of parathyroid hormone (PTH) within 24 hours in predicting post-operative hypocalcemia after total thyroidectomy. METHOD: In this study, we selected 207 consecutive patients, performed total thyroidectomy in our hospital, measured the serum PTH and electrolyte, divided them into subgroups according to the definition of post operative hypocalcemia, and made the ROC curves analysis combining with clinical data. RESULT: The mean value of pre-operative PTHs between groups. show no significant difference (P > 0.05); in the first day after surgery, the post operative hypocalcemia group have a significant lower average PTHs (P < 0.01). ROC area under the curve (AUC) of day-1 is 0.886, with the PTH cutoff value 16. 8 pg/ml. CONCLUSION: The PTH within 24 hours is an important indicator to judging post-operative hypocalcermia after total thyroidectomy. PMID- 27197454 TI - [Expression and clinical pathological implications of carbonic anhydrase 9 and P glycoprotein in laryngeal squamous cell carcinoma]. AB - OBJECTIVE: To identify the difference of CA IX and P-gp expression level between laryngeal squamous cell carcinoma (LSCC) and benign tissues, evaluate the relationship of these two proteins in LSCC, and their correlation with clinical and pathological features. METHOD: Immunohistochemical detection of CA IX and P gp were performed in 47 cases of LSCC and 20 cases of vocal cord polyps. RESULT: Overexpression of CA IX and P-gp both in LSCC and in vocal cord polyp (P < 0.05) were confirmed, with a correlation between the two proteins in LSCC (r = 0.324, P < 0.05). The expression of CA IX was related to clinical staging and lymph node metastasis in LSCC (P < 0.05). While P-gp was related to clinical staging and histological grading in LSCC (P < 0.05). CONCLUSION: The overexpression of CA IX and P-gp may play a role in LSCC progression. PMID- 27197455 TI - [Effectiveness of cisplatin on the expressions of Bcl-2 and Bax in cochlea and spiral ganglion cells of guinea pigs]. AB - OBJECTIVE: To investigate the effectiveness of cisplatin on the expressions of Bcl-2 and Bax in cochlea and spiral ganglion cells (SGC) of guinea pigs. METHOD: Twenty guinea pigs were randomly divided into cisplatin (n = 10) and control groups (n = 10). Cisplatin group were administrated with a dose of intraperitoneal injection of 16 mg/kg, while the control group were received intraperitoneal injection of normal saline as placebo. Before and 7 days following injections, the ototoxic effect was measured with distortion product otoacoustic emission (DPOAE). Bcl-2, Bax in cochlea were detected by Western Blot. Immunohistochemical staining was used to detect the protein levels of Bcl-2 and Bax in spiral ganglion cells. RESULT: In control and cisplatin group, Bcl-2 protein levels were 0.727 8 +/- 0.016 9 and 0.467 6 +/- 0.020 1, Bax protein levels were 0.384 8 +/- 0. 0217 and 0.735 6 +/- 0.022 3 in cochlea respectively, both P < 0.01. In Control and cisplatin group, the grey values of Bcl-2 in SGC were 99.00 +/- 2.42 and 149.80 +/- 2.37 respectively, the grey values of Bax were 154.50 +/- 2.80 and 104.50 +/- 3.09 respectively, both P < 0.05. CONCLUSION: Decreased expression of Bcl-2 and increased expression of Bax may be involved in cisplatin-induced apoptosis in cochlea and SGC of guinea pigs. PMID- 27197457 TI - [Analysis of allergens characteristic in 1172 patients with allergic rhinitis in Changzhou area]. AB - OBJECTIVE: To determine the distribution of allergens in patients with allergic rhinitis during from 2008 to 2015 in Changzhou area. METHOD: Allergy Screen method was used to detect the specifical-allergen IgE levels of 1172 patients with allergic rhinitis. Among the patients, the distribution of all allergens was analyzed. The positive rate was compared with age, gender, season and so on. RESULT: The most common allergens in allergic rhinitis patients in Changzhou were dust mite, fungus, house dust, milk, dander of dog, weed mixture, farina and dander of cat. The more higher positive rates of dust mite, fungus, house dust, milk, dander of dog, dander of cat, eggs were found in teenager group than adult group (P < 0.05). There were more higer positive rates of weed mixture, farina, cashew, cockroaches and crab in teenager group than adult group (P < 0.05). There was no significant difference of positive rate between female group and male group. There was significant difference of variation with seasons. CONCLUSION: Dust mite, fungus and house dust were the most common allergens among patiens with allergic rhinitis in Changzhou area. The positive rates of allergens varied with ages and seasons. PMID- 27197458 TI - [The evaluation of nasal ventilatioan in patients with obstructive sleep apnea hypopnea syndrome after nasal cavity ventilation expansion techniques by using acoustic rhinometry]. AB - OBJECTIVE: To evaluate nasal ventilation in patients with obstructive sleep apnea hypopnea syndrome (OSAHS) after nasal cavity ventilation expansion techniques by using acoustic rhinometry. METHOD: Thirty-eight patients with mild OSAHS and 17 patients with moderate OSAHS who were diagnosis by PSG were selected. The acoustic rhinometry and rhinomanometry were used to assess the nasal cavity volumes (NCV), nasal airway resistance (NR), nasal minimal cross-section area (NMCA) and distance of nasal minimal cross-section area from nostril (DCAN) before and after the surgery (6 month later). RESULT: The state of mild OSAHS group in NCV, NMCA and NR: before surgery (2.41 +/- 1.33) cm3, (0.37 +/- 0.39) cm2, (2.07 +/- 1.48) cmH2O/(L . min), after surgery (2.53 +/- 1.54) cm3, (0.45 +/ 0.34) cm2, (1.69 +/- 1.03) cmH2O/(L . min), has significant difference (P < 0.05). The state of moderate OSAHS group in NCV, NMCA and NR: before surgery (2.03 +/- 1.54)cm3, (0.29 +/- 0.39) cm2, (3.47 +/- 2.56) cmH2O/(L . min), after surgery (2.31 +/- 1.47) cm3, (0.39 +/- 0.33) cm2, (1.89 +/- 1.03)cmH2O/(L . min), also has significant difference (P < 0.05), while DCAN in two group had no difference (P > 0.05). CONCLUSION: There was an objective evaluation of nasal ventilation in OSAHS patients after surgery by using acoustic rhinometry. PMID- 27197456 TI - [Experimental studies for botulinum toxin type A to antagonist the VIP/PACAP expression on nasal mucosa in allergic rhinitis rat]. AB - OBJECTIVE: To explore the expression and significance of vasoactive intestinal peptide and Pituitary adenylate cyclase activiting polypeptide (VIP/PACAP) of nasal mucosa in rats with allergic rhinitis (AR), and the function of botulinum toxin-A(BTX-A) to inhibit the expression of VIP/PACAP in AR. METHOD: Thirty Sprague-Dawley rats were randomly divided into 3 groups, which were the AR group, the intervention group, and the control group. In the AR group, ovalbumin was used to sensitize healthy rats. In the intervention group, BTX-A was dripped into the nasal cavity of AR rats 7 times. In the control group, only physiological saline was used to drip into the nasal cavity of AR rats. Changes of the rats' behavior were observed. ELISA were used to detected the concentration variation of serum IFN-gamma and IL-4. Histopathology and immunohistochemistry were employed to observe morphology in the rats' nasal mucosal and the expression of VIP/PACAP. Statistical analysis was also made. RESULT: (1)The typical symptoms marks of nasal scratching, sneezing, nasal blockage and rhinorrhea of AR group (7.5 +/- 0.50) were higher than intervention group (1 +/- 0.27) and control group (0.8 +/- 0.31). (2) Comparing to intervention group and control group, the serm IFN-gamma of the AR group obvious reduced (P < 0.05), the serm IL-4 of the AR group obvious rose (P < 0.01), and the serm Th1/Th2 (IFN-gamma/IL-4) of the AR group obvious reduced (P < 0.01). (3) Comparing to intervention group and control group, the cilium loss, inflammatory cells infiltration, and inflammatory cells exudation of nasal mucosa in AR group were more obviously (P < 0.01), and the intervention group of the 3 indexes was obviously than control group. (4) The expression of VIP in the rats' nasal mucosa of the AR group (13.27 +/- 2.74) were more intense than intervention group (5.21 +/- 2.18) and control group (3.56 +/- 5.30) (P < 0.01), and the expression of PACAP in the rats' nasal mucosa of the AR group (20.97 +/- 2.14) were more intense than intervention group (6.33 +/- 3.04) and control group (4.63 +/- 1.25) (P < 0.01). (5) In all the 3 groups, there was positive correlation between expression of negative in VIP/PACAP and Thl/Th2 cell infiltration(r were respectively -0.340 and -0.223, P < 0.05). CONCLUSION: The VIP/PACAP in the rats' nasal mucosa may play an important role in pathogenesis of AR, and BTX-A could improve the symptoms of AR through inhibition of the expression of VIP/ PACAP. PMID- 27197460 TI - [3.0 T MRI observe the ears and sinus damage degree of patients with acute carbon monoxide poisoning]. AB - OBJECTIVE: Through 3.0 T MRI study the ear and sinus lesions of patients with acute carbon monoxide poisoning. METHOD: From 2012 to 2015 collected the MRI images of the 45 patients with acute carbon monoxide poisoning, observe their changes of middle ear and mastoid and sinus imaging. RESULT: The middle ear injury of mastoid 41 cases (91.1%), 22 cases (48.9%) of maxillary sinus injury, ethmoid sinus injury in 20 cases (44.4%), sphenoid sinus 9 cases (20.0%), 5 cases (11.1%) of frontal sinus injury. Carbon monoxide poisoning patients according to clinical symptoms can be divided into light, medium and heavy 3 groups, observing the ear sinus damage degree for comparison between groups, found to have significant differences (P < 0.05). CONCLUSION: The patients with acute carbon monoxide poisoning ear and sinus injury should cause the attention of the medical staff, MRI can reflect people's ears from the details and the damage degree of the sinuses. PMID- 27197459 TI - [Expression and significance of MTDH and MMP-9 in laryngeal squamous cell carcinoma]. AB - OBJECTIVE: To observe the expression changes of metadherin (MTDH) and matrix metalloproteinase-9 (MMP-9) in the laryngeal squamous cell carcinoma tissues and to investigate the significance. METHOD: The expression of MTDH and MMP-9 in 54 cases of laryngeal squamous cell carcinoma tissues(observation group) and 30 cases of para-carcinoma tissues (control group) was examined by immunohistochemical method, the correlation between them and their correlations with the clinicopathological parameters were analyzed. RESULT: The positive expression rates of MTDH in the observation group and control group were 64.8% (35/54) and 6.7% (2/30), respectively; the positive expression rates of MMP-9 in the observation group and control group were 70.4% (38/ 54) and 13.3% (4/30), respectively; and there was a statistically significant difference between two groups (all P < 0.01). In the laryngeal squamous cell carcinoma tissues, the expression of MTDH protein was related with degree of differentiation, lymph-node metastasis and TNM stage (all P < 0.05); and the expression of MMP-9 protein was related lymph-node metastasis and TNM stage (all P < 0.05). The expression of MTDH was positively correlated with MMP-9 in the laryngeal squamous cell carcinoma tissues (r = 0.371, P < 0.01). CONCLUSION: The high expression of MTDH and MMP-9 was closely related to the occurrence, development and metastasis of laryngeal squamous cell carcinoma, joint detection of the two proteins was valuable for early diagnosis and prognosis of laryngeal squamous cell carcinoma. PMID- 27197461 TI - [Diagnosis and treatment of laryngeal carcinosarcoma (attached one case report)]. PMID- 27197462 TI - [Hypofibrinogenemia caused by hemocoagulase after endoscopic sinus surgery: a case report]. AB - A 61 year-old male patient, plasma fibrinogen level was 2.98 g/L, endoscopic sinus surgery was performed under general anesthesia for polypoid of uncinate process with mycotic maxillary sinusitis. Hemocoagulase were given in pre- and post-operative for treatment. The patient was found postoperative drain blood continuously since 3 days after surgery, when the dose of hemocoagulase reach 26 KU, and fibrinogen determined in Plasma was 0.48 g/L. Coagulation returned to normal and nasal bleeding stopped after discontinuation of the hemocoagulase and supplement with fibrinogen. PMID- 27197463 TI - [Extramedullary relapse of acute lymphoblastic leukemia in the mastoid after allogeneic hematopoietic stem cell transplantation: a case report]. AB - Extramedullary relapse of acute lymphoblastic leukemia (ALL) in the mastoid after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is rare. In this paper, we describe such an uncommon case of extramedullary relapse of ALL in the mastoid. The patient, who had been diagnosed as having ALL and underwent an allo HSCT from his matched sibling donor. Eight months after allo-HSCT, he presented with ear-ache, tinnitus. The middle ear mastoid CT revealed otomastoiditis. The patient underwent operation. After pathological examination, the definited diagnosis was made that the patient was extramedullary relapse of ALL in the mastoid. We should pay more attention to the patients with hemopathy, which can help to improve early diagnosis. PMID- 27197464 TI - [Distant metastases to maxillary sinus from an unknown lung adenocarcinoma: a cases report]. AB - A 59-year-old man was admitted to the Department of Ear, Nose and Throat with a complaint of six-month history of left facial numbness and toothache. There was no special previous medical history in addition to smoking. No obvious abnormality in routine electrocardiogram, chest X-ray, abdominal B ultrasound were found. (1) CT scans showed heterogeneous shadows in maxillary sinus with the lesions on the left max- illary bone and evidently destruction of alveolar bone. The histopathological examination revealed bone tissue which was partly covered by an intact adenocarcinoma cell. (2) Immunohistochemical staining foe CK7, CD117, thyroid transcription factor-1, and novel aspartic proteinase A were positive and thus compatible with metastatic lung adenocarcinoma. (3) Chest CT scans showed a 1 cm x 2 cm mass on the superior lobe of the left lung, with destruction of sternum and rib, confirming that the lesions in the paranasal sinuses were lung cancer metastases. Therefore, this patient conclusively diagnosed as lung adenocarcinoma with multiple bone metastases. PMID- 27197465 TI - [Pleomorphic adenoma of the nasal septum: a case report]. AB - We report a rare case of pleomorphic adenoma arising from the nasal septum. A 37 year-old woman presented with a 1-year-history of right-sided occasional epistaxis. Computed tomographic scans revealed an oval mass in the right nasal cavity. The tumor was removed endoscopically with endonasal approach. The microscopic finding showed numbers of myoepithelial cells and duct-like structures consisting of loose myxoid stroma. This lesion had histological characteristics of a pleomorphic adenoma, and this was confirmed by immunohistochemical expression of cytokeratin, S-100 protein and SMA. Her post operative course was uneventful, and she is currently free from the disease 1.5 years after surgery. PMID- 27197466 TI - [Supernumerary nasal tooth a case report]. AB - This case report describes a male patient, 5 years old, with recurrent nose congestion and fetid discharge from the right nasal cavity. The suspected clinical diagnosis of a supernumerary nasal tooth was confirmed by computed tomography (CT). Laboratory examination showed normal. After endoscopic removal in general anesthesia, the tooth was examined by pathological examination. A literature search identified 22 supernumerary nasal teeth in 21 patients. PMID- 27197467 TI - [Research progress on the management of no packing after septoplasty]. AB - Packing the nose after septoplasty is common practice. The use of postoperative packing has been proposed to reduce the dead space between the subperichondrial flaps and minimize postoperative complications such as hemorrhage, septal hematoma, and formation of synechiae. Additionally, postoperative packing is thought to stabilize the remaining cartilaginous septum and minimize persistence or recurrence of septal deviation. Despite these theoretic advantages, evidence to support the use of postoperative packing is lacking. Additionally, nasal packing is not an innocuous procedure. The use of nasal packing actually cause these complications such as postop- erative pain, mucosal injury, bleeding, worsening of breathing due to sleep disorders, and postoperative infections. Routine use of anterior nasal packing after septoplasty should be challenged for not presenting proven benefit. As alternatives to traditional packing, septal suturing, septal stapler and fibrin glue have been used recently. The purpose of this article is to summarize the progress of traditional packing to no packing after septoplasty. PMID- 27197468 TI - [The review on voice disorders and rehabilitation in teachers of primary and secondary school]. AB - Nowadays, various voice disorders are sprung out towards teachers of primary and secondary school, affecting their personal life and social work. Through literature review, the author aims at clearing up series of assessments and methods of voice training which are suitable for the teachers of primary and secondary school, such as establishing a right way of respiratory, phonation and resonance, avoiding occupational risk factors such as vocal abuse or misuse to regain healthy voice. Review of the several relevant literature and commentary about voice disorders of the teachers in primary and secondary school. Although various methods of voice training were reported from time to time to guide us SLP to carry out voice therapy, however, deviations of the clinical data from scholars' different points of view are waiting for our further support through case-control study. PMID- 27197469 TI - [The progress of inner ear malformation in radiological research]. AB - Inner ear malformations are anomalies linking to development insults at different periods of embryogenesis,which are common causes of congenital sensorineural hearing loss. The evaluation of pediatric sensorineural hearing loss mostly depends on high-resolution computed tomography and magnetic resonance imaging, which can excellently depict the temporal bones and inner ear malformations. PMID- 27197470 TI - [Proposal and discussion on the concept of traumatic plastic surgery]. PMID- 27197471 TI - [Classification and operation in the treatment of maxillary retrusion of adult patients with cleft lip and palate]. AB - OBJECTIVE: To classify the patients with cleft lip and palate who need orthognathic surgery and to propose the corresponding operations. METHODS: From January 2005 to May 2015, 121 patients with cleft lip and palate diagnosed as maxillary retrusion were treated by orthognathic surgery. Inclusion criteriar: (1) male aged over 16, female aged over 14; (2) diagnosed as non-syndromic cleft lip and palate without systemic disease and other genetic diseases; (3) without previous orthodontic and orthognathic treatment; (4) having no other craniofacial malformation. Maxillary features and repaired types were recorded. RESULTS: 93 patients were included and divided into two categories depended on the dental crowding. Class I: the teeth quantity and bone quantity is coordinated, space analysis <= 4 mm (mild dental crowding). The forward distance of maxillary less than 6 mm was defined as Class I a (36 cases) more than 6 mm as Class I b (28 cases). Class II: the teeth quantity and bone quantity is not coordinated, space analysis > 4 mm ( moderate or severe dental crowding). After the simulation of distraction osteogenesis, the anterior crossbite was corrected defined as Class II a (23 cases), not corrected defined as Class II b (6 cases). Class I a were corrected by conventional orthognathic surgery. While Class I b were corrected by Le Fort I maxillary advancement using distraction osteogenesis. Class II a were repaired just by anterior maxillary distraction. While Class II b need to combine conventional orthognathic surgery with anterior maxillary distraction. All the patients were satisfied with the treatment effect. CONCLUSIONS: The patients of cleft lip and palate with maxillary retrusion who need orthognathic surgery can be classified as the method mentioned above, and then choose the appropriate operations. PMID- 27197472 TI - [Extensive cranioplasty for sagittal synostosis in young children by preserving multiple cranial bone flaps adhered to the dura mater: experience with 63 cases]. AB - OBJECTIVE: This study aimed to evaluate the effort of applying frontal and occipital bones in extensive cranioplasty and preserving multiple cranial bone flaps adhered to the dura mater in the treatment of sagittal synostosis. METHODS: From April 2008 to June 2013, sixty-three children with sagittal synostosis, aged 5 months to 3 years, were included in the study. The frontal bone flap was removed using an air drill. The occipital and bilateral temporal bone flaps were cut open but not detached from the dura mater or fixed to produce floating bone flaps. The skull bone was cut into palisade-like structures. Brain compression from both sides and the base of the skull was released and the brain expanded bilaterally through the enlarged space. Only a long strip-shaped bone bridge remained in the central parietal bone. Subsequently, the frontal bone flaps and occipital bone flap were pushed towards the midline and fixed with the parietal bone bridge to shorten the anteroposterior diameter of the cranial cavity and allow the brain to expand bilaterally to correct scaphocephaly. The CT images showed that both sides of the parietal bone of artificial sagittal groove gradually merged postoperative 1 year, and skull almost completely normal healing after operation 2 or 3 years, without deformity recurrence within 5 years. Among them all, 61 children's intelligence is normal and 2 children's lagged behind normal level, no further improvement. RESULTS: Patients were followed up 1 - 5 years (an average of 43 months). Skull growth was excellent in all patients, the anteroposterior diameter was shortened by 14.6 mm averagely, the transverse diameter was increased by 12.3 mm averagely, the prominent forehead was corrected, and scaphocephaly improved significantly. There were no complications such as death and skull necrosis. CONCLUSIONS: The application of frontal and occipital bones in extensive cranioplasty and preserving multiple cranial bone flaps adhered to the dura mater can be used in the treatment of sagittal synostosis. Surgery without removing bone flaps is less traumatic and results in no massive bleeding. It can effectively relieve brain compression and promotes transversal expansion of the brain during surgery and subsequent normal brain development. PMID- 27197473 TI - [Combined surgery and sclerotherapy for massive venous malformations of the tongue]. AB - OBJECTIVE: To explore the curative effect of surgery and selerotherapy for massive venous malformations of the tongue. METHODS: From January 2005 to December 2014, subtotal resection or debulking for 15 cases of massive venous malformation in the tongue was undertaken with multiple sessions of pre- and post operative injection therapy of pingyangmycin, lauromacrogol and absolute ethanol. RESULTS: All signs associated with the lesions including eating, sleep and speech disorders disappeared after treatment. Complete or near complete resolution was achieved in 9 cases, and a significant reduction in size in a further 6 cases after surgical excision and peri-operative sclerotherapy. CONCLUSIONS: For massive venous malformations of the tongue, surgical excision combined with multiple sessions of sclerotherapy is a good treatment option. PMID- 27197474 TI - [Advanced orbicularis oculi muscle flap for eyelid defect]. AB - OBJECTIVE: To investigate the application and therapeutic effect of advanced orbicularis oculi muscle (OOM ) flap for eyelid defect. METHODS: Uni-pedicle or bi-pedicle advanced OOM flaps were designed according to the location, depth and size of the eyelid defects. The resulted wounds in the donor sites were closed directly. The flap size ranged from 1.5 cm x 0.5 cm - 6.0 cm x 3.5 cm. RESULTS: 120 cases were treated. All the flaps survived except for 3 flaps with epidermis necrosis at the end of flaps, which healed after dressing. The patients were followed up for 3 -36 months with inconspicious scar in donor sites. The flap color, texture had a good match with surrounding skin. CONCLUSIONS: The OOM flap is ideal for eyelid defect with reliable blood supply, satisfied color and texture. The wound at donor site can be closed directly with less morbidity. PMID- 27197475 TI - [Clinical analysis of epicanthus correction with two methods: Z-plasty and Y-V plasty]. AB - OBJECTIVE: To compare the clinical effects of different surgical methods for the epicanthus corrective surgery. METHODS: Canthoplasty with asymmetric Z-flap is applied in 46 cases, Y-V advancement procedure for epicanthoplasty is applied in 42 cases. The epicanthus aesthetic measurement were measured and calculated by software before and after surgery, the diameter of the iris was measured as a reference value,and the postoperative scar was assessed by VSS scale. At the same time, by measuring the lateral canthal distance, the accuracy of the measurement method can be verified. RESULTS: All patients were satisfied with the long-term results and there were no recurrences of the epicanthal fold. The shortening ratio of the ICD is 8.36% in the group with the Z-plasty, and 5.88% in Y-V plasty. the lateral canthal distance have no diffrence before and after surgery. CONCLUSIONS: Two surgical methods can get good results. The magnitude of correction in Z-plasty may larger than Y-V plasty, but postoperative retraction may existed in Z plasty. PMID- 27197476 TI - [Costal cartilage for rhinoplasty]. AB - OBJECTIVE: Augmentation rhinoplasty is a commonly procedure in clinical work for a plastic surgeon. Autologous costal cartilage is widely used in aesthetic rhinoplasy because of the abundant in quality. However, the cartilage may warp, and it is not easy-handling for inexperienced plastic surgeons. We-used diced cartilage combined with thin strips as columellar struts, which can be easily shaped, and reduce the warping incidence. METHODS: From July 2012 to March 2014, 61 patients were performed diced costal cartilage for nasal augmentation via endonasal approach. Standardized photographs are obtained before and after surgery. Postoperative outcome is graded by patient's self-evaluation of the nasal appearance with a satisfaction scale. RESULTS: Among the 61 cases, 25 were revision cases. The follow-up time was no less than 6 months, with an average time of 10.9 months. 28 patients reported improved or better nasal appearance. One patient required revision surgery because of overcorrection. Supratip step off was observed in one patient and corrected by external reshaping. No warping, infection, irregularity, absorption, airway obstruction, or donor-site morbidity were observed. All patients were satisfied with the final appearance. CONCLUSIONS: Diced costal cartilage is a reliable option for nasal augmentation and revision rhinoplasty. Good outcomes can be achieved postoperatively, with aesthetically pleasing appearance and simple procedure. PMID- 27197477 TI - [Anthropometric analysis of facial aging in 1200 Han adult people in Dalian]. AB - OBJECTIVE: To investigate the facial aging analysis of 1200 Han adult people in Dalian with iris diameter, so as to provide reference for facial rejuvenation in Han people. METHODS: 1200 facial digital photographs from the second-generation ID card of China were stratified randomly selected as the research sample, excluding facial deformity, tattooing eyebrow, tattooing lid margin, ptosis, lip grain and eyebrow deformity cases, as well as the cases whose join point of upper eyelid and lower eyelid not exposed at the nasal side. These photos were divided into six cohorts: female aged 18, 38, and 68 years old; and male aged 18, 38, and 68 years old, with 200 cases in each cohort. The individual iris diameter was divided into 20 equal parts in each photograph, with each part marked one unit as individual iris diameter ruler. Ten values were made from a horizontal plane between the medial canthus to ten points at one face ( the line between two medial canthus is used as the horizontal line, circumocular and facial soft tissue were measured with individual iris diameter ruler on the photographs), then the results were analyzed with Adobe Photoshop software. RESULTS: There are statistically significant differences in eyebrow height (36.42 +/- 4.22 unit in 18 years old male group, 40.22 +/- 6.90 unit in 38 years old male group, 34.83 +/ 9.39 unit in 68 years old male group; 37.59 +/- 6.72 unit in 18 years old female group, 41.09 +/- 5.15 unit in 38 years old female group, 36.84 +/- 9.45 unit in 68 years old female group), palpebral fissure height, physiognomic external canthus height, palpebral fissure width, pupil height and other items (P < 0.05). CONCLUSIONS: (1) The brow position rises to the peak level at middle age (38 years old group), then drops down gradually with aging. (2) The physiognomic external canthus moves towards the nasal side and caudal side with aging. (3) Eyeball moves towards caudal side with aging. (4) The soft tissue around bilateral angle of mouth, nasal tip and submaxilla moves towards caudal side with aging. (5) The measurement of individual iris diameter ruler can apply to analyze the aging changes of facial soft tissue, and is more suitable for the case when facial photographs are taken at different distances. PMID- 27197478 TI - [Reconstruction of soft tissue defects at nose, lip, and cheek with facial artery perforator flaps]. AB - OBJECTIVE: To investigate the therapeutic effect of facial artery perforator flap for the soft tissue defects at nose, lip and cheek. METHODS: The facial artery perforator adjacent to the defect was identified by Doppler ultrasonography. The perforator flap was designed according to the defect location, size and shape. The subcutaneous tissue around the perforator was kept as much as possible to protect the venous drainage. RESULTS: From Oct. 2012 to Oct.2013, 26 cases were treated with facial artery perforator flaps, with 9 cases of nasal defects, 10 cases of lip defects and 7 cases of buccal defects. The defects size ranged from 1.5 cm x 2.0 cm to 3.0 cm x 3.0 cm and the flaps size ranged from 2.0 cm x 2.5 cm to 3.5 cm x 3. 5 cm. Superficial necrosis(3mm in width) happened at the end of one flap. All the other 25 flaps survived completely. 16 cases were followed up for 3 months to 2 years with no relapse and satisfactory cosmetic and functional results were achieved. CONCLUSIONS: Both cosmetic and functional effect can be achieved with facial artery perforator flap for defects at nose, lip and cheek. PMID- 27197479 TI - [Large facial defect reconstruction with partition pre-expanded cervico-scapulo dorsal flaps based on the superficial cervical artery]. AB - OBJECTIVE: To assess the outcome of large facial defect reconstruction with "partition" pre-expanded cervico-scapulo-dorsal flaps (CSDF) based on the superficial cervical artery (SCA). METHODS: Surgical course consisted of 3 stages. In stage I, a skin flap was designed along the axis of SCA according to the facial defect and an expander was implanted in the cervico-scapulo-dorsal region by means of "partition" expansion. The expanders were implanted beside the flap axis and beneath the posterior half of flaps so as to expand only half area of the flap. During the stage II, expanders were injected with saline regularly for continuous expansion. In stage III, the pre-expanded CSDFs were transferred to cover the facial defect of which the CSDFs included about half of non-expanded area. RESULTS: From November of 2008 to December of 2013, 15 patients with facial hypertrophic scar or scar contracture were reconstructed with pre-expanded CSDF based on the SCA. The expansion lasted for 3 to 4 months, and the expanded volume varied from 680 to 960 ml. One case of 4.0 cm x 1.5 cm epidermal flap necrosis occurred and healed subsequently with superficial scar; and another case of blister formation in the distal part of flap was found, which recovered without scar; the other 13 flaps survived without complications. After a follow-up for 12 to 38 months( average 26. 2 months), patients regained satisfactory appearance of face, with no obvious hypertrophic scar in the donor site. CONCLUSIONS: Partition preexpanded CSDF based on the SCA is a good choice for large facial defect reconstruction, and the partition expansion is an effective strategy for prevention of venous congestion. PMID- 27197480 TI - [Correction of cryptotia and cartilage malformation with Z-plasty without skin grafting]. AB - OBJECTIVE: To explore the curative effect of Z-plasty without skin grafting for correction of cryptotia. METHODS: Twenty-five cases (29 ears) with cryototia were corrected by Z-plasty without skin grafting in our department from June 2009 to January 2014. A Z-shaped incision with one arm on the back of antihelix and the other arm on the edge of hair was made on the back of ear and scalp. The adhesion on the back of antihelix cartilage was dissected and the cartilage framework was lifted and re-positioned. The postauricular flap was transferred to cover the wound on the back of antihelix. The other flap was transferred to cover the remnant wound and correct the malformation of cryptotia. RESULTS: All the patients were followed up from 6 months to 1 year with stable and symmetric appearance. CONCLUSIONS: The shape of auricle is natural after operation without skin grafting. It is a simple and ideal method for the treatment of cryptotia. PMID- 27197481 TI - [Application of trans-areola approach for costicartilage harvesting]. AB - OBJECTIVE: To investigate the trans-areola approach for costicartilage harvesting in order to avoid the obvious scar resulted by traditional approach through chest incision. METHODS: From 2013, 7 cases who underwent rhinoplasty received costicartilage harvesting through trans-areola approach. The incision was designed along the lower interior edge of right areola. Then the dissection was performed to expose the 5th costicartilage. Then a costicartilage, 2 - 5 cm in length, was harvested. The incision was closed delicately. The suture was removed 7 days after operation. RESULTS: The patients were followed up for 3 months to 2 years without hypertrophic scar and breast deformity. The scar was located in conceal location. The satisfactory rate was higher than that in patients with chest incision. CONCLUSIONS: The scar resulted from trans-areola approach is comparatively conceal, compared with that at chest. PMID- 27197482 TI - [Application of V shape flap for the urethral external meatus and glanuloplasty]. AB - OBJECTIVE: To discuss the methods for urethral external meatus and glanuloplasty after correction of hypospadias. METHODS: The V shape flap on the dorsal side of glan, combined with the bilateral glan flaps were moved to the ventral side. The flap at the ventral side of urethral external meatus was turned over. Then the urethral external meatus was repositioned to the top end of glan with the ventral defects covered by the dorsal flaps. Then the coniform glan was reconstructed. RESULTS: From January 2008 to December 2013, 28 cases were treated, including glandular hypospadias, postoperative retraction of external urethral meatus and meatal stenosis. 21 patients were followed up for 1 -12 months (average, 1 month) with marked improvement of glan appearance and retraction of external meatus. No meatal stenosis happened. CONCLUSIONS: Postoperative retraction of urethral external meatus and meatal stenosis can be corrected by V shape flap on the dorsal side of glan combined with the bilateral glan flaps. The flat appearance of glan can be improved. It is an ideal method for glandular hypospadias. PMID- 27197483 TI - [Whole-genome sequencing on one case of Han familial keloids]. AB - OBJECTIVE: To screen SNP information of keloid pedigrees through whole genome sequencing. METHODS: We Collected information and clinical data of the keloid pedigree and constructed charts of the pedigree. The DNA was extracted from peripheral venous blood samples of the pedigree to sequence the whole genome. RESULTS: 27 SNP and 8 disease-associated genes were screened out. CONCLUSIONS: Whole genome sequencing technology can select new genetic mutations associated with keloid, and provide a new way for the research of keloid. PMID- 27197484 TI - [Establishment of an in vitro culture model of single human hair follicle]. AB - OBJECTIVE: To establish an in vitro culture model of single human hair follicle, and observe their morphological and histological changes. METHODS: Human hair follicles were isolated from the volunteer patients. After dissecting follicles into single, follicles in growth phase were cultured in Williams E without any serum. This experiment included 3 groups: single follicle without sebaceous gland and other surrounding tissue (control group); single follicle with sebaceous gland and without the other surrounding tissue( experiment group A); single follicles with sebaceous gland and the other surrounding tissue (experiment group B). The survival rate, survival time, growth rate, multiplication capacity and apoptosis of cultured follicles and their morphological and histological changes were observed sequentially. RESULTS: The hair follicles in experiment groups showed a better viability and a higher growth rate than those in control group. And the follicles in group B could keep growing for more than 25 days, which was longer than those in group A. Moreover, the sebaceous gland and the other surrounding tissue in group B showed great induction effect on follicle-cell proliferation and anti-apoptosis. CONCLUSION: The in vitro culture model of signal human hair follicles (single follicles including epidermis, sebaceous gland and the other surrounding tissue) had optimized internal environment which is similar to in vivo internal environment. PMID- 27197485 TI - [Effects of AQP1 overexpression on morphology and water transport in mouse Schwann cells]. AB - OBJECTIVE: To determine the effect of AQP1 gene on facial nerve edema following injury through investigation of the relationship between the expression of AQP1 gene and Schwann cells swelling. METHODS: The AQP1 expression in Schwann cells of mouse facial nerve tissues was detected by immunofluorescent staining. The transgenic protocol by lentivirus transduction was used to specifically upregulate AQP1 expression in Schwann cells. Lenti-AQP1 and CTRL (empty vector) transduced cells were observed during gene overexpression every 24 h for 6 days by using phase contrast microscopy. Cell volume of CTRL and Lenti-AQP1 treated cells was measured daily from the day of treatment, through day 6. RESULTS: Schwann cell primary cultures maintained a high level of AQP1 water channels, representing an ideal cell model to study the role of AQP1 in the facial nerve. The expression of AQP1 mRNA and protein in Schwann cells infected with the Lenti AQP1 was increased significantly compared with CTRL lentivirus (P < 0.05). Lenti AQP1 caused cell swelling in cultured Schwann cells, as validated by cell volume determinations (P < 0.01). CONCLUSIONS: AQP1 is an important factor responsible for the fast water transport of cultured Schwann cells. It plays an important role in facial nerve edema. PMID- 27197486 TI - [Research on Shielding of Emboli with the Phase-Controlled Ultrasound]. AB - The postoperative neurological complications is associated with intraoperative cerebral emboli, which results from extracorporeal circulation and operation. It can effectively reduce the incidence of neurological complications with ultrasonic radiation. In fluids, a particle will change it's motion trail when it is acted by the radiation force generated by the ultrasound. This article mainly discuss how to shielding emboli with ultrasound. The equipment can transmit phased ultrasonic signals, which is designed on a FPGA development board. The board can generate a square wave, which is converted into a sine wave through a power amplifier. In addition, the control software has been developed on Qt development environment. The result indicates it's feasible to shielding emboli with ultrasonic radiation force. This article builds a strong foundation for the future research. PMID- 27197487 TI - [Research on PPG Signal Reconstruction Based on Compressed Sensing]. AB - In order to improve the storage and transmission efficiency of dynamic photoplethysmography (PPG) signals in the detection process and reduce the redundancy of signals, the modified adaptive matching pursuit (MAMP) algorithm was proposed according to the sparsity of the PPG signal. The proposed algorithm which is based on reconstruction method of sparse adaptive matching pursuit (SAMP), could improve the accuracy of the sparsity estimation of signals by using both variable step size and the double threshold conditions. After experiments on the simulated and the actual PPG signals, the results show that the modified algorithm could estimate the sparsity of signals accurately and quickly, and had good anti-noise performance. Contrasting with SAMP and orthogonal matching pursuit (OMP), the reconstruction speed of the algorithm was faster and the accuracy was high. PMID- 27197488 TI - [Influence of Width and Thickness of DCI's Curved Section on Its Performance]. AB - By establishing a series of Dynamic Cervical Implants (DCI) within C5-C6 cervical spinal segments, the biomechanical finite element analysis for DCI with different width and thickness were carried out to investigate the influence of the width and thickness of DCI's curved section on its equivalent stress and range of motion (ROM), so as to provide some theoretical basis for the optimization of DCI's design. The results show that the width of DCI's curved section has more obvious influence on the ROM of lateral bending and torsion, in comparison with the thickness of DCI's curved section. By appropriate reduction in width, the ROMs of lateral bending and torsion increase obviously, i.e. the overall movement function of patients is improved. Furthermore, the increase of equivalent stress could be counteracted by corresponding increase of thickness. PMID- 27197489 TI - [Discussion on Quality Evaluation Method of Medical Device During Life-Cycle in Operation Based on the Analytic Hierarchy Process]. AB - The content related to the quality during life-cycle in operation of medical device includes daily use, repair volume, preventive maintenance, quality control and adverse event monitoring. In view of this, the article aims at discussion on the quality evaluation method of medical devices during their life cycle in operation based on the Analytic Hierarchy Process (AHP). The presented method is proved to be effective by evaluating patient monitors as example. The method presented in can promote and guide the device quality control work, and it can provide valuable inputs to decisions about purchase of new device. PMID- 27197490 TI - [Study on Accurately Controlling Discharge Energy Method Used in External Defibrillator]. AB - This paper introduces a new method which controls discharge energy accurately. It is achieved by calculating target voltage based on transthoracic impedance and accurately controlling charging voltage and discharge pulse width. A new defibrillator is designed and programmed using this method. The test results show that this method is valid and applicable to all kinds of external defibrillators. PMID- 27197491 TI - [Detection of Heart Rate of Fetal ECG Based on STFT and BSS]. AB - Changes in heart rate of fetal is function regulating performance of the circulatory system and the central nervous system, it is significant to detect heart rate of fetus in perinatal fetal. This paper puts forward the fetal heart rate detection method based on short time Fourier transform and blind source separation. First of all, the mixed ECG signal was preprocessed, and then the wavelet transform technique was used to separate the fetal ECG signal with noise from mixed ECG signal, after that, the short-time Fourier transform and the blind separation were carried on it, and then calculated the correlation coefficient of it, Finally, An independent component that it has strongest correlation with the original signal was selected to make FECG peak detection and calculated the fetal instantaneous heart rate. The experimental results show that the method can improve the detection rate of the FECG peak (R), and it has high accuracy in fixing peak(R) location in the case of low signal-noise ratio. PMID- 27197492 TI - [Improvement of Digital Capsule Endoscopy System and Image Interpolation]. AB - Traditional capsule image collects and transmits analog image, with weak anti interference ability, low frame rate, low resolution. This paper presents a new digital image capsule, which collects and transmits digital image, with frame rate up to 30 frames/sec and pixels resolution of 400 x 400. The image is compressed in the capsule, and is transmitted to the outside of the capsule for decompression and interpolation. A new type of interpolation algorithm is proposed, which is based on the relationship between the image planes, to obtain higher quality colour images. capsule endoscopy, digital image, SCCB protocol, image interpolation PMID- 27197493 TI - [Design and Implementation of a Programmable Wireless Neural Stimulation System]. AB - The paper proposes and realizes a programmable wireless neural stimulation system which can be used as a solution of functional electrical stimulation to treat neural diseases. The system is composed of two parts: controller and neural stimulator. The controller can transmit pulse parameters to the stimulator wirelessly, and the stimulator can generate bidirectional pulses with charge balance. The simulator takes use of ADCs to sample on the bidirectional pulse output, which compared with preset amplitude to the DAC output voltage to realize the voltage calibration. Through the test, the whole system works stably and the output of the biphasic charge balanced circuit is definite. The stimulator output ranges from 0 to 5 V ajustably, and the frequency ranges from 1 Hz to 200 Hz ajustably, while the pulse width ranges from 500 MUs to 1500 MUs ajustably. The duration of the stimulation can be set from 10 s to 10 min. PMID- 27197494 TI - [Development of a New Type Elastic Syndesmosis Hook Plate]. AB - OBJECTIVE: To design a kind of internal fixation device to treat the syndesmosis injury. METHODS: The elastic syndesmosis hook plate is made of medical stainless steel alloy, which is consisted of locking or common screw fixing hole of the tibial side for the head, tridentate fork like arc anatomical fibula side plate for the tail and serpentine elastic connecting body. By reduction of the joint of the lower tibia and fibula, the steel plate tail is fixed at the side of the fibula and the head is fixed at the side of the tibia for fixing the symphysis. RESULTS: The design of elastic syndesmosis hook plate is reasonable, and the operation is convenient. There is no need to penetrate the substantia ossea and the plate has elastic micro-movement feature, the problem of internal fixation breakage and loosening is avoid in huge degree, so it is safe and reliable. CONCLUSION: The elastic syndesmosis hook plate is a new type medical apparatus of internal fixation of the symphysis, which is worthy of clinical popularization and application. PMID- 27197495 TI - [Research of the Thrombus Protection Device During the Cerebral Vascular Interventional Therapy]. AB - This article introduces a cerebral thrombus protection device for the cerebral interventional treatment, also introduces the principle, design and manufacturing process of the device, and confirmes the effectiveness in vitro experiment. PMID- 27197496 TI - [Design of Huge Data Repository Platform Based on Children Infectious Diseases]. AB - Taking children respiratory infectious diseases as the research object, CDSS transform from isolated clinical data to an integration Model. With integrating pharmacy and laboratory knowledge, the system establishes children typical characterization data of common infectious diseases and medical efficacy data repository to providing treatment recommendations for doctor. Based on the clinical characteristics of children infectious diseases, this paper proposes knowledge inference engine and an information integration model. decision-making inference engine, medical information integration model. PMID- 27197497 TI - [A USB-Based Digital ECG Sensor]. AB - Based on the ECG-specific BMD 101 integrated circun chip, this study designed a digital ECG sensor. In practical application, users just need to connect the ECG sensor 'o upper computer (such as PC or mobile phone) through USB interface, to realize the functions including display, alarm, saving, transfer etc. After tests, They demonstrate that the sensor can be applied to the detection of arrhythmia, such as bigeminy coupled rhythm, proiosystole etc. Besides, the sensor has various advantages in monitoring an managing the heart health of people out of hospital, including low cost, small volume, usableness, simplicity of operation etc. PMID- 27197498 TI - [Development of an Independent Heater for Ventilator Tube]. AB - Nowadays, normal humidifier is used to heat and humidify the gas before sending to ventilator tube. A new type of ventilator which offers both breathing tube with heater and humidifier is incorporate. In the light of this, patients already bought ventilator still confront this problem. Therefore, this paper mainly introduces a new manufactural method which is controlling the temperature and humidity of gas sent by breathing machine online by a temperature controller which consist of Silica gel hotline and microcomputer. As a matter of fact, the controller is adaptable in various types of breathing tube and can accurately control the humidity and temperature of gas sent into bodies. PMID- 27197499 TI - [Multifunctional Nursing Beds Based on Intelligent Detection and Recovery]. AB - With the advent of the aging society, there will be a wide range of applications if novel intelligent multifunctional nursing beds can be developed for hospitals, bead houses and families at the same time. By listing and analyzing existing products, this paper summarized four function categories for multifunctional nursing beds, including security assurance, treatment aid, comfortability optimization, and human-machine interaction and communication. Finally, by comparing existing functions and potential user requirements, this paper proposed four function development trends, including physiological parameter monitoring, sleep aid, intelligent temperature control, and video communication. PMID- 27197500 TI - [The Clinical Application Status and Development Trends of Hydrogen Peroxide Low Temperature Plasma Sterilizers]. AB - The hydrogen peroxide low temperature plasma sterilization technology solved the problems of thermo-sensitive materials' disinfection and sterilization based on its development and unique characteristics. This paper introduced the researches of clinical application quality control, and showed the hydrogen peroxide low temperature plasma sterilizers were being widely used in hospitals and highly recognized. According to the clinical data and the literatures of the domestic equipment in preliminary application, it could be concluded that the technology maturity of domestic hydrogen peroxide low temperature plasma sterilizers was in a high level. The advantages of using domestic hydrogen peroxide low temperature plasma sterilizers to do disinfection and sterilization included lower cost, safer, faster and non-toxic, etc. Also the management system should be improved and the clinical staff should master the technical essentials, obey the procedures strictly, verify periodically and offer full monitoring to upgrade the quality of sterilization. PMID- 27197501 TI - [Study on the Detection Rate of Cell and Linearity Performance Detection Method in the CellSearch System]. AB - Research on CellSearch system's detection rate of cells and linearity performance detection method, so as to analyze the accurate and reasonable detection method to meet the CellSearch characteristics of the system. PMID- 27197502 TI - [The Requirements of Medical Device Market Access in India]. AB - This paper introduces the premarket registration procedures and the post market regulatory requirements in India. According to Indian medical device act and related medical regulations on medical device, this is a preliminary discussion on the registration management system to provide referance for foreign medical device to enter India market. PMID- 27197503 TI - [Research on How to Extend the Testing Capacities of the Provincial Institutes for Medical Devices]. AB - This article introduces the current status of Chinese institutes for medical devices testing, and analyses the misunderstanding in extending the testing capacities for the provincial institutes for medical devices. Then, some suggestions are given to orientate themselves in extending capacities. Finally, these specific procedures on extending the testing capacities are presented. PMID- 27197504 TI - [Preliminary Study on Error Control of Medical Devices Test Reports Based on the Analytic Hierarchy Process]. AB - In this paper, the common errors in medical devices test reports are classified and analyzed. And then the main 11 influence factors for these inspection report errors are summarized. The hierarchy model was also developed and verified by presentation data using MATLAB. The feasibility of comprehensive weights quantitative comparison has been analyzed by using the analytic hierarchy process. In the end, this paper porspects the further research direction. PMID- 27197505 TI - [The Traceability Management for Qualification Documents of Medical Instruments]. AB - The management for qualification documents of medical instruments is very important work to management department of medical instruments. Because the number of qualification documents of medical instruments is very large and they have an expiry date, it is difficult to manage them. This article discussed how to manage qualification documents of medical instruments, and an information management system that has a function of traceability management has been developed. This information management system standardizes management for qualification documents of medical instruments, and ensures that qualification documents of medical instruments are available and can be traced. Besides, it can reduce the amount of work for medical instruments management. PMID- 27197506 TI - [Development and Application of Triple Cannula Dual-Lumen Vacuum Extractor]. AB - OBJECTIVE: Design and make triple cannula dual-lumen vacuum extractor to improve effect of decompression in operation of intestinal obstruction. METHODS: Triple cannula dual-lumen vacuum extractor was applied in 32 patients who underwent operation of intestinal obstruction from 2012 to 2015 in our hospital. The effect of intestinal decompression and patient prognosis were observed. RESULTS: 32 patients that used triple cannula dual-lumen vacuum extractor had good recovery except for one patient abdominal incision with fatty liquefaction. The other patients had one-stage healed without any complication such as intestinal fistula, abdominal infection etc. CONCLUSION: Application of triple cannula dual lumen vacuum extractor in operation for intestinal decompression could avoid contamination of abdomen and injury of intestinal mucosa, which had satisfied effect of intestinal decompression and promoted the effect of operation for intestinal obstruction. PMID- 27197507 TI - [Evaluation of Medical Instruments Cleaning Effect of Fluorescence Detection Technique]. AB - OBJECTIVE: To compare the cleaning effect of automatic cleaning machine and manual cleaning on coupling type surgical instruments. METHODS: A total of 32 cleaned medical instruments were randomly sampled from medical institutions in Putuo District medical institutions disinfection supply center. Hygiena System SUREII ATP was used to monitor the ATP value, and the cleaning effect was evaluated. RESULTS: The surface ATP values of the medical instrument of manual cleaning were higher than that of the automatic cleaning machine. CONCLUSION: Coupling type surgical instruments has better cleaning effect of automatic cleaning machine before disinfection, the application is recommended. PMID- 27197508 TI - [Observation and Repairment of Tidal Volume Abnormal Fault of Anesthesia Machine]. AB - Anesthesia machine is an important equipment of clinical surgery. This paper introduces several abnormal conditions of the anesthesia machine, especially the judgment and the common fault check of the tidal volume for reference. PMID- 27197509 TI - Ibrutinib is a safe and effective therapy for systemic mantle cell lymphoma with central nervous system involvement - a multi-centre case series from the United Kingdom. PMID- 27197510 TI - Training of breast surgical oncologists. AB - Breast surgical oncology is a defined sub-specialty of general surgery with focus on the surgical management of breast disease and malignancy within a multidisciplinary context. Much of the training of breast surgical oncologists in the United States exists within a fellowship training structure with oversight and approval by the Society of Surgical Oncology (SSO). Rapid continuous changes in breast oncology practice have further substantiated dedicated expertise in breast surgical oncology. Training programs are structured to develop proficiency in fellows for advanced surgical techniques and clinical decision-making as well as exposure to the multidisciplinary aspects of breast cancer management. Components of a successful program include an intense multidisciplinary curriculum, engagement in clinical research and attention to strong mentorship. National curriculum and training requirements as well as supplemental resources assist in standardizing the fellowship experience. As surgical training and the field of breast oncology continues to evolve, so do fellowship training programs to ensure high quality breast surgical oncologists equipped to deliver high quality evidence based patient care while continuing to drive future research and trainee education. PMID- 27197511 TI - Organizing a breast cancer database: data management. AB - Developing and organizing a breast cancer database can provide data and serve as valuable research tools for those interested in the etiology, diagnosis, and treatment of cancer. Depending on the research setting, the quality of the data can be a major issue. Assuring that the data collection process does not contribute inaccuracies can help to assure the overall quality of subsequent analyses. Data management is work that involves the planning, development, implementation, and administration of systems for the acquisition, storage, and retrieval of data while protecting it by implementing high security levels. A properly designed database provides you with access to up-to-date, accurate information. Database design is an important component of application design. If you take the time to design your databases properly, you'll be rewarded with a solid application foundation on which you can build the rest of your application. PMID- 27197512 TI - Contemporary management of ductal carcinoma in situ and lobular carcinoma in situ. AB - The management of in situ lesions ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS) continues to evolve. These diagnoses now comprise a large burden of mammographically diagnosed cancers, and with a global trend towards more population-based screening, the incidence of these lesions will continue to rise. Because outcomes following treatment for DCIS and LCIS are excellent, there is emerging controversy about what extent of treatment is optimal for both diseases. Here we review the current approaches to the diagnosis and treatment of both DCIS and LCIS. In addition, we will consider potential directions for future management of these lesions. PMID- 27197513 TI - Ultrasound image-guided core biopsy of the breast. AB - Results of partial mastectomy or lumpectomy including margin negativity are improved when preoperative diagnosis is obtained. This article describes the various techniques, instruments, utility and complications of the techniques. Emphasis is given to ultrasound (US) usefulness and effectiveness. PMID- 27197514 TI - The role of Advanced Practice Providers in interdisciplinary oncology care in the United States. AB - Advanced Practice Registered Nurses (APRNs) and Physician Assistants (PAs), generally referred to as Advanced Practice Providers (APPs), are fundamental to interdisciplinary oncology care. As the projected demand for oncology services is anticipated to outpace the supply of oncologists, APPs will become increasingly vital in the delivery of oncology care and services. The training, education, and scope of practice for APPs gives the interdisciplinary care team professionals that deliver high-quality clinical services and provide valuable contributions and leadership to health care quality improvement initiatives. Optimizing the integration of APPs in oncology care offers immense advantages towards improvement of clinical outcomes. PMID- 27197515 TI - The way to precision medicine of our team. AB - In the past few years, the treatment model of breast cancer (BC) has undergone a variety of changes and the change of eras. Whether the classification treatment which is currently dominant, or the precision medicine which is extremely promising in the future are both carrying out the concept of individual treatment. Through retrospect the research and clinical achievement of our team in the past three decades, we share our experience and exertion on the exploration of a road to BC precision medicine in this paper and make a prospect of the future development direction of research and treatment. PMID- 27197516 TI - A Thematic Analysis of Stigma and Disclosure for Perinatal Depression on an Online Forum. AB - BACKGROUND: Perinatal mental illness is a global health concern; however, many women do not get the treatment they need to recover. Some women choose not to seek professional help and get no treatment because they feel stigmatized. Online forums for various health conditions, including perinatal mental health, can be beneficial for members. Little is known about the role that online forums for perinatal mental illness play in reducing stigma and subsequent disclosure of symptoms to health care providers and treatment uptake. OBJECTIVE: This study aimed to examine stigma and disclosure in forums and describe any potential disadvantages of forum use. METHODS: An online forum for mothers was examined and 1546 messages extracted from 102 threads from the antenatal and postnatal depression section. These messages were subjected to deductive systematic thematic analysis to identify common themes regarding stigma and disclosure of symptoms and potential disadvantages of forum use. RESULTS: Two major themes were identified: stigma and negative experiences of disclosure. Stigma had 3 subthemes: internal stigma, external stigma, and treatment stigma. Many women were concerned about feeling like a "bad" or "failed" mother and worried that if they disclosed their symptoms to a health care provider they would be stigmatized. Posts in response to this frequently encouraged women to disclose their symptoms to health care providers and accept professional treatment. Forum discourse reconstructed the ideology of motherhood as compatible with perinatal mental illness, especially if the woman sought help and adhered to treatment. Many women overcame stigma and replied that they had taken advice and disclosed to a health care provider and/or taken treatment. CONCLUSIONS: Forum use may increase women's disclosure to health care providers by challenging their internal and external stigma and this may strengthen professional treatment uptake and adherence. However, a few posts described negative experiences when disclosing to health care providers. PMID- 27197518 TI - The Second International Conference on Nutrition, as Seen by a Member State. AB - For years now, providing people with food and balanced diets has been a problem unsolved by the world community. Despite numerous initiatives, the great breakthrough has still not happened, not least because the issue is so complex. Hunger and undernourishment must be fought as much as hidden hunger, overweight and obesity. Increasingly, several forms of malnutrition have been occurring simultaneously. The so-called double burden of malnutrition has become the new normal. The follow-up process of the Second International Conference on Nutrition assumes a vital role in that context. The Rome Declaration and the Framework for Action commit the international community, international organizations and civil society to undertake joint efforts across and beyond sectorial policies. Both documents also indicate numerous starting points for actions that consider individual national examples. Germany has been actively engaged at both the national and the international levels. Since its inception in 2008, the National Action Plan 'IN FORM' has taken up a number of suggestions made by the Second International Conference on Nutrition. While IN FORM is further developed, the ideas given in the Framework for Action shall provide a fresh impetus. Within its development cooperation, Germany is increasingly focusing on improving the nutritional situation, such as through its One World, No Hunger initiative. In the follow-up process, all stakeholders, including the Food and Agriculture Organization and the World Health Organization, will have to offer platforms to promote exchange among all parties involved and to initiate coherent actions that also reach beyond national borders. Only then can the improvement of the nutritional situation really be seen as a truly global challenge. Given the issue's complexity, it is equally important to establish priorities in each case in order for progress not to be thwarted by lengthy decision-making processes. Improving the situation of particularly vulnerable groups, such as young women and small children, shall be as prominent as the support and promotion of diversified agriculture. Building networks among partners is of equal importance for joint action and exchange between stakeholders at the national and international levels to generate added value on the way toward solving the nutrition problem. Science will also have to be more closely involved for that matter and purpose. Research is required to supply scientific evidence for certain measures to be taken, and it assumes a prominent role where political consultation, knowledge management and the implementation of measures are concerned. PMID- 27197517 TI - Shrinking the malaria map in China: measuring the progress of the National Malaria Elimination Programme. AB - BACKGROUND: Remarkable progress has been made towards the elimination of malaria in China since the National Malaria Elimination Programme (NMEP) was launched in 2010. The incidence of locally-acquired malaria cases has declined rapidly and endemic areas have also dramatically shrunk. In total, 3 078 malaria cases were reported in 2014, but only 56 cases were indigenous. In order to further promote the elimination programme, we reviewed the progress of and experiences associated with malaria elimination in China, and identified the challenges and priorities for the next stage of the programme. METHODS: Data were collected from the web based China Information System for Disease Control and Prevention, and the China Annual Report of Malaria Elimination. The progress towards the elimination of malaria from 2010 to 2014 was measured. RESULTS: During the implementation of the NMEP from 2010 to 2014, local malaria incidence has declined continuously, only remaining in the Yunnan Province and Tibet Autonomous Region in 2014. By the end of 2015, 75.6 % (1 636/2 163) of the malaria-endemic counties passed the sub national elimination assessment. The main challenges are cases of border malaria and imported malaria from other countries. Sustainable support and investment from the government, the establishment of an effective surveillance and response system, and risk assessments for the potential reintroduction of malaria are priorities for the next stage of the elimination programme. CONCLUSIONS: The NMEP in China has been successfully implemented thus far and the malaria map has shrunk dramatically. The priorities for malaria elimination are interventions to block transmission at border areas, management of imported malaria cases, preventing malaria reintroduction, capacity building, and sustainability of malaria surveillance and response. PMID- 27197519 TI - Long-Term Outcomes of the Implant of a Periurethral Constrictor for Stress Urinary Incontinence Following Radical Prostatectomy. AB - OBJECTIVES: To assess morbidity, effectiveness and quality of life (QoL) of implant of Silimed periurethral constrictor (PC) in a consecutive series of patients who had stress urinary incontinence following radical prostatectomy. MATERIAL AND METHODS: A prospective non-randomized study designed on patients who underwent implant of Silimed PC. Primary end point was postoperative morbidity and secondary end points were effectiveness of implant and QoL. We performed a sub-analysis of men who received previous radiation and we compared the subpopulation with radiation-naive patients. RESULTS: Nineteen patients (31.6%) received pelvic radiation therapy prior implant. All procedures were completed successfully with median operative time of 55 (IQR 50-62.5) min. We recorded 47 (78.3%) postoperative complications in 30 men. Twenty-three men (38.3%) developed urethral erosion at median follow-up of 27.5 (IQR 21-35) months, and 1 man (1.9%) had rectourethral fistula at 2 months. Risk of urethral erosion increased significantly among patients who received radiation (63.1 vs. 26.8%; p < 0.001). In 12 cases (20%), we recorded malfunctioning of the reservoir requiring replacement. CONCLUSION: The implant of Silimed device is not safe due to a high risk of urethral erosion. Careful patient selection and detailed counseling are mandatory when considering the implant of PC in adult patients. PMID- 27197520 TI - Patient positioning during percutaneous tracheostomy using an air-inflated pressure bag. PMID- 27197521 TI - The venous-arterial CO2 to arterial-venous O2 content difference ratio: Easy to monitor? AB - Blood sampling for venous-arterial CO2 to arterial-venous O2 content difference ratio starts to be widely used as a hemodynamic monitoring tool, despite that this calculation remains cumbersome. We propose using indirect calorimetry and respiratory quotient for this purpose, with the same physiological concept. PMID- 27197522 TI - Determinants of Child Malnutrition and Infant and Young Child Feeding Approaches in Cambodia. AB - Women's diets often decrease with regard to amounts per meal and day as well as diversity if a household's access to food is limited. The result is a monotonous diet that, in particular, negatively affects women's nutritional status during pregnancy and lactation and, thus, the infant. The infant's diet is of utmost importance, as it needs to meet the nutrient requirements especially during the first 2 years of life, a critical window for the child's healthy development. In Cambodia, infant and young child feeding (IYCF) practices are poor. Preparation of a special complementary meal in addition to breast milk feeds for children aged 6-23 months is often not a common habit. Instead, children eat watery, plain rice porridges that do not meet the nutrient requirements at this young age. A lack of adequate caring practices such as responsive feeding exacerbates the risk of malnutrition. Caregivers are often unaware of the importance of nutrition during the first 2 years of life regarding its effects on children's growth. In 2012, a randomized controlled trial (RCT) was started in two provinces of northern Cambodia: Oddar Meanchey and Preah Vihear. To contribute to reducing child mortality by addressing malnutrition among children 6-23 months of age, the Food and Agriculture Organization of the United Nations (FAO) implemented a nutrition-sensitive agriculture project with nutrition-specific actions, i.e. a nutrition education intervention was embedded in a food security project. Wealth, a child's age, and maternal education were identified as determinants of a child's dietary diversity. The older the child and/or the wealthier the household, the more diverse the child's diet. Maternal education was positively associated with the child's dietary diversity. Household dietary diversity was significantly associated with child dietary diversity in a model including group, child's age, maternal education, and wealth as confounders. The RCT also showed that a 2- to 3-month nutrition education programme carried out by government and community health volunteers as well as local NGOs addressing caregivers with a child between 5 and 18 months of age has great potential to improve IYCF practices. Since no impact on average height-for-age Z-scores could be demonstrated in this RCT, we suggest for Cambodia that (1) more emphasis be put on animal-source food and other protein sources in nutrition education, (2) nutrition education be implemented in the community through trained government and community members including peers as trainers, (3) sessions on family nutrition be included in the curriculum and the continuation of breastfeeding be emphasized, and (4) nutrition education be institutionalized, including continuous in-service training for sustainability. PMID- 27197524 TI - Diagnostic Accuracy of BRAF Immunohistochemistry in Colorectal Cancer: a Meta Analysis and Diagnostic Test Accuracy Review. AB - The aim of this study was to evaluate the concordance between the BRAF (V600E) mutation test and immunohistochemistry (IHC) and to evaluate the diagnostic accuracy of BRAF IHC for colorectal cancer (CRC) through a systematic review, meta-analysis, and diagnostic test accuracy review. The current study included 1021 CRCs from eight eligible studies. The concordance rates were investigated between BRAF IHC and the mutation test. In addition, diagnostic test accuracy review was conducted and calculated using the value of area under curve (AUC) on the summary receiver operating characteristic (SROC) curve. The positive rate of BRAF IHC was 30.5 % (range; 13.2-66.2 %), and the BRAF mutation was found in 30.2 % (range; 11.7-66.2 %). The overall concordance rate between BRAF IHC and the mutation test was 0.944 (95 % confidence interval (CI) 0.873-0.977). In the BRAF IHC-positive and -negative groups, the concordance rates between BRAF IHC and the mutation test were 0.895 (95 % CI 0.800-0.945) and 0.956 (95 % CI 0.878-0.985), respectively. The pooled sensitivity and specificity were 0.94 (95 % CI 0.91 0.96) and 0.96 (95 % CI 0.95-0.98), respectively. The diagnostic odds ratio was 272.86 (95 % CI 46.11-1614.88), and the value of AUC on SROC curve was 0.9846. Taken together, our results suggest that BRAF IHC is strongly concordant with the BRAF mutation test and has high diagnostic accuracy in BRAF mutation analysis of CRCs. Further cumulative studies on detailed evaluation criteria are needed before application in daily practice. PMID- 27197523 TI - The role of the addition of ovarian suppression to tamoxifen in young women with hormone-sensitive breast cancer who remain premenopausal or regain menstruation after chemotherapy (ASTRRA): study protocol for a randomized controlled trial and progress. AB - BACKGROUND: Ovarian function suppression (OFS) has been shown to be effective as adjuvant endocrine therapy in premenopausal women with hormone receptor-positive breast cancer. However, it is currently unclear if addition of OFS to standard tamoxifen therapy after completion of adjuvant chemotherapy results in a survival benefit. In 2008, the Korean Breast Cancer Society Study Group initiated the ASTRRA randomized phase III trial to evaluate the efficacy of OFS in addition to standard tamoxifen treatment in hormone receptor-positive breast cancer patients who remain or regain premenopausal status after chemotherapy. METHODS: Premenopausal women with estrogen receptor-positive breast cancer treated with definitive surgery were enrolled after completion of neoadjuvant or adjuvant chemotherapy. Ovarian function was assessed at the time of enrollment and every 6 months for 2 years by follicular-stimulating hormone levels and bleeding history. If ovarian function was confirmed as premenopausal status, the patient was randomized to receive 2 years of goserelin plus 5 years of tamoxifen treatment or 5 years of tamoxifen alone. The primary end point will be the comparison of the 5 year disease-free survival rates between the OFS and tamoxifen alone groups. Patient recruitment was finished on March 2014 with the inclusion of a total of 1483 patients. The interim analysis will be performed at the time of the observation of the 187th event. DISCUSSION: This study will provide evidence of the benefit of OFS plus tamoxifen compared with tamoxifen only in premenopausal patients with estrogen receptor-positive breast cancer treated with chemotherapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00912548 . Registered May 31 2009. Korean Breast Cancer Society Study Group Register KBCSG005 . Registered October 26 2009. PMID- 27197526 TI - Is the Risk of Ovarian Malignancy Algorithm Better Than Other Tests for Predicting Ovarian Malignancy in Women with Pelvic Masses? AB - AIM: The study aimed to compare the risk of ovarian malignancy algorithm (ROMA) with risk of malignancy index (RMI), cancer antigen 125 (CA125), human epididymis protein 4 (HE4) and Sassone ultrasonography (US) score in predicting ovarian cancer (OC) in women who present with pelvic or adnexal masses. METHODS: Pelvic US, serum CA125 and HE4 levels were investigated preoperatively in consecutively enrolled Thai women over 18 years with clinically diagnosed pelvic or adnexal masses who were undergoing elective surgery at a super tertiary hospital in Thailand in 2012. ROMA, RMI and Sassone US score were calculated. RESULTS: Of 260 women who were evaluated, 74 had OC. Areas under the receiver operating characteristic curve (AUC) in predicting OC were ROMA, 86.2%; RMI, 87.6%; CA125, 80.6%; HE4, 82.4%; and Sassone score, 77.1%. ROMA and RMI performed similarly well (AUCs 84.4 and 85.6%) in premenopausal women but RMI outperformed ROMA in postmenopausal women (AUCs 87.9 and 84.0%, respectively). At the conventional cutoff value, ROMA and CA125 showed the highest sensitivity (83.8%) but HE4 had the highest specificity (86.0%). CONCLUSIONS: ROMA was comparable to RMI in predicting OC. Either ROMA or RMI can be applied to women with pelvic masses, stratified into low- and high-risk groups for OCs. PMID- 27197525 TI - Attention deficit-hyperactivity disorder is associated with reduced blood pressure and serum vitamin D levels: results from the nationwide German Health Interview and Examination Survey for Children and Adolescents (KiGGS). AB - Alterations in blood pressure in attention-deficit/hyperactivity disorder (ADHD), specifically during dopaminergic stimulant intake, are not fully understood. It has been reported that vitamin D deficiency might modify dopaminergic pathways and thus influence ADHD symptoms. Using data from the nationwide German Health Interview and Examination Survey for Children and Adolescents (KiGGS) study, we compared blood pressure and vitamin D levels in healthy controls to both diagnosed ADHD patients and suspected ADHD subjects, as defined by a value of >=7 on the hyperactivity-inattention subscale of the Strengths and Difficulties Questionnaire. In a total cohort of n = 6922 study participants aged 11-17 years, mean arterial blood pressure was significantly higher in controls (86.7 +/- 8.2 mmHg) than in the two groups of confirmed (85.5 +/- 7.8 mmHg, p = 0.004, n = 430) and suspected ADHD patients (84.6 +/- 8.2, p < 0.001, n = 399). In addition, we found an inverse association between vitamin D and blood pressure in both ADHD groups (p < 0.003). Regression analyses adjusted for age, sex, body-mass index, psychotropic medication use, and serum vitamin D levels confirmed that low blood pressure was a significant and independent predictor of ADHD. Furthermore, we observed that vitamin D mediated the effect of systolic blood pressure on ADHD diagnosis (b = 0.007, 95 % confidence interval [CI] 0.001-0.013, p = 0.021, R 2 = 0.050). In a large and representative national sample of German adolescents, we found a significant association between low blood pressure and ADHD symptoms. In addition, we observed that circulating vitamin D mediated the inverse relation between blood pressure and ADHD, although the effect size was very low. These findings highlight the role of dysregulated pathways of the autonomic nervous system in ADHD. PMID- 27197527 TI - Masked repetition priming hinders subsequent recollection but not familiarity: A behavioral and event-related potential study. AB - The present study used the masked repetition priming paradigm in the study phase and the R/K paradigm in the test phase to investigate whether repetition priming can hinder recognition memory and which recognition process (familiarity or recollection) is hindered. Event-related potentials (ERPs) in the study and test phase were recorded to explore the temporal course of how repetition priming hinders subsequent recognition memory and which old/new effect (FN400 or LPC) is affected. Converging behavioral and ERP results indicated that masked repetition priming hindered subsequent recollection but not familiarity. The analysis of ERP priming effects in the study phase indicated that primed words were associated with less negative N400 and less positive LPC compared to unprimed words. The analysis of the priming effect as a function of subsequent memory revealed that only the LPC priming effect was predictive of priming effect on subsequent memory, which suggested that the "prediction-error" account might be a possible explanation of how repetition priming affects subsequent recognition memory. PMID- 27197528 TI - Government is starting to recognise pressures on general practice, GPs told. PMID- 27197529 TI - Patient-tailored analysis of minimal residual disease in acute myeloid leukemia using next-generation sequencing. AB - Next-generation sequencing techniques have revealed that leukemic cells in acute myeloid leukemia often are characterized by a limited number of somatic mutations. These mutations can be the basis for the detection of leukemic cells in follow-up samples. The aim of this study was to identify leukemia-specific mutations in cells from patients with acute myeloid leukemia and to use these mutations as markers for minimal residual disease. Leukemic cells and normal lymphocytes were simultaneously isolated at diagnosis from 17 patients with acute myeloid leukemia using fluorescence-activated cell sorting. Exome sequencing of these cells identified 240 leukemia-specific single nucleotide variations and 22 small insertions and deletions. Based on estimated allele frequencies and their accuracies, 191 of these mutations qualified as candidates for minimal residual disease analysis. Targeted deep sequencing with a significance threshold of 0.027% for single nucleotide variations and 0.006% for NPM1 type A mutation was developed for quantification of minimal residual disease. When tested on follow up samples from a patient with acute myeloid leukemia, targeted deep sequencing of single nucleotide variations as well as NPM1 was more sensitive than minimal residual disease quantification with multiparameter flow cytometry. In conclusion, we here describe how exome sequencing can be used for identification of leukemia-specific mutations in samples already at diagnosis of acute myeloid leukemia. We also show that targeted deep sequencing of such mutations, including single nucleotide variations, can be used for high-sensitivity quantification of minimal residual disease in a patient-tailored manner. PMID- 27197532 TI - Anidulafungin-Induced Suicidal Erythrocyte Death. AB - BACKGROUND/AIMS: The novel antifungal drug Anidulafungin is used for the treatment of diverse fungal infections including candidiasis and aspergillosis. The traditional antifungal drug amphotericin B has previously been shown to trigger eryptosis, the suicidal death of erythrocytes characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include increase of cytosolic Ca2+ activity ([Ca2+]i), oxidative stress, ceramide, activated protein kinase C (PKC), casein kinase 1alpha or p38 kinase and activated caspases. Inhibitors of eryptosis include nitric oxide (NO). The present study explored, whether Anidulafungin induces eryptosis. METHODS: Flow cytometry was employed to estimate phosphatidylserine abundance at the erythrocyte surface from annexin-V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, abundance of reactive oxygen species (ROS) from DCFDA dependent fluorescence, and ceramide abundance at the erythrocyte surface utilizing specific antibodies. Hemolysis was quantified by measuring haemoglobin concentration in the supernatant. RESULTS: A 48 hours exposure of human erythrocytes to Anidulafungin (1.5 - 6 ug/ml) significantly increased hemolysis and the percentage of annexin-V-binding cells, and significantly decreased forward scatter. Anidulafungin (6 ug/ml) slightly, but significantly inceased Fluo3-fluorescence and the effect of Anidulafungin on annexin-V-binding was slightly, but significantly blunted by removal of extracellular Ca2+. The effect of Anidulafungin on annexin-V-binding was further significantly blunted by the p38 kinase inhibitor SB203580 (2 uM) and NO donor nitroprusside (1 uM). An increase of extracellular K+ concentration significantly blunted the effect of Anidulafungin on cell volume but not on annexin-V-binding. Anidulafungin rather decreased DCFDA fluorescence and the effect of Anidulafungin on annexin-V-binding was not significantly blunted by the antioxidant N acetylcysteine (1 mM). Moreover, the effect of Anidulafungin on annexin-V-binding was not paralleled by significant increase of ceramide abundance and was not significantly blunted by PKC inhibitor staurosporine (1 uM), casein kinase 1alpha inhibitor D4476 (10 uM) or pancaspase inhibitor zVAD (10 uM). CONCLUSIONS: Anidulafungin triggers hemolysis and eryptosis with cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect in part due to Ca2+ entry and activation of p38 kinase. PMID- 27197533 TI - Gender Transformative Approaches to Engaging Men in Gender-Based Violence Prevention: A Review and Conceptual Model. AB - Engaging men and boys as participants and stakeholders in gender-based violence (GBV) prevention initiatives is an increasingly institutionalized component of global efforts to end GBV. Accordingly, evidence of the impact of men's engagement endeavors is beginning to emerge, particularly regarding interventions aimed at fostering gender equitable and nonviolent attitudes and behaviors among men. This developing evidence base suggests that prevention programs with a "gender transformative" approach, or an explicit focus on questioning gender norms and expectations, show particular promise in achieving GBV prevention outcomes. Interventions targeting attitude and behavior change, however, represent just one kind of approach within a heterogeneous collection of prevention efforts around the globe, which can also include community mobilization, policy change, and social activism. The degree to which gender transformative principles inform this broader spectrum of men's engagement work is unclear. The goals of this article are twofold. First, we offer a conceptual model that captures and organizes a broader array of men's antiviolence activities in three distinct but interrelated domains: (1) initial outreach and recruitment of previously unengaged males, (2) interventions intended to promote gender-equitable attitudes and behavior among men, and (3) gender equity-related social action aimed at eradicating GBV, inclusive of all genders' contributions. Second, we review empirical literature in each of these domains. Across these two goals, we critically assess the degree to which gender transformative principles inform efforts within each domain, and we offer implications for the continuing conceptualization and assessment of efforts to increase men's participation in ending GBV. PMID- 27197531 TI - Extracellular ATP protects pancreatic duct epithelial cells from alcohol-induced damage through P2Y1 receptor-cAMP signal pathway. AB - Extracellular adenosine-5'-triphosphate (ATP) regulates cell death and survival of neighboring cells. The detailed effects are diverse depending on cell types and extracellular ATP concentration. We addressed the effect of ATP on ethanol induced cytotoxicity in epithelial cells, the cell type that experiences the highest concentrations of alcohol. Using pancreatic duct epithelial cells (PDEC), we found that a micromolar range of ATP reverses all intracellular toxicity mechanisms triggered by exceptionally high doses of ethanol and, thus, improves cell viability dramatically. Out of the many purinergic receptors expressed in PDEC, the P2Y1 receptor was identified to mediate the protective effect, based on pharmacological and siRNA assays. Activation of P2Y1 receptors increased intracellular cyclic adenosine monophosphate (cAMP). The protective effect of ATP was mimicked by forskolin and 8-Br-cAMP but inhibited by a protein kinase A (PKA) inhibitor, H-89. Finally, ATP reverted leakiness of PDEC monolayers induced by ethanol and helped to maintain epithelial integrity. We suggest that purinergic receptors reduce extreme alcohol-induced cell damage via the cAMP signal pathway in PDEC and some other types of cells. PMID- 27197530 TI - Combined effects of smoking and HPV16 in oropharyngeal cancer. AB - BACKGROUND: Although smoking and HPV infection are recognized as important risk factors for oropharyngeal cancer, how their joint exposure impacts on oropharyngeal cancer risk is unclear. Specifically, whether smoking confers any additional risk to HPV-positive oropharyngeal cancer is not understood. METHODS: Using HPV serology as a marker of HPV-related cancer, we examined the interaction between smoking and HPV16 in 459 oropharyngeal (and 1445 oral cavity and laryngeal) cancer patients and 3024 control participants from two large European multi-centre studies. Odds ratios and credible intervals [CrI], adjusted for potential confounders, were estimated using Bayesian logistic regression. RESULTS: Both smoking [odds ratio (OR [CrI]: 6.82 [4.52, 10.29]) and HPV seropositivity (OR [CrI]: 235.69 [99.95, 555.74]) were independently associated with oropharyngeal cancer. The joint association of smoking and HPV seropositivity was consistent with that expected on the additive scale (synergy index [CrI]: 1.32 [0.51, 3.45]), suggesting they act as independent risk factors for oropharyngeal cancer. CONCLUSIONS: Smoking was consistently associated with increase in oropharyngeal cancer risk in models stratified by HPV16 seropositivity. In addition, we report that the prevalence of oropharyngeal cancer increases with smoking for both HPV16-positive and HPV16-negative persons. The impact of smoking on HPV16-positive oropharyngeal cancer highlights the continued need for smoking cessation programmes for primary prevention of head and neck cancer. PMID- 27197535 TI - Part I: Checkpoint inhibitors in cancer therapy. PMID- 27197534 TI - Using Dual Fluorescence Reporting Genes to Establish an In Vivo Imaging Model of Orthotopic Lung Adenocarcinoma in Mice. AB - PURPOSE: Lung adenocarcinoma is characterized by a poor prognosis and high mortality worldwide. In this study, we purposed to use the live imaging techniques and a reporter gene that generates highly penetrative near-infrared (NIR) fluorescence to establish a preclinical animal model that allows in vivo monitoring of lung cancer development and provides a non-invasive tool for the research on lung cancer pathogenesis and therapeutic efficacy. PROCEDURES: A human lung adenocarcinoma cell line (A549), which stably expressed the dual fluorescence reporting gene (pCAG-iRFP-2A-Venus), was used to generate subcutaneous or orthotopic lung cancer in nude mice. Cancer development was evaluated by live imaging via the NIR fluorescent signals from iRFP, and the signals were verified ex vivo by the green fluorescence of Venus from the gross lung. The tumor-bearing mice received miR-16 nucleic acid therapy by intranasal administration to demonstrate therapeutic efficacy in this live imaging system. RESULTS: For the subcutaneous xenografts, the detection of iRFP fluorescent signals revealed delicate changes occurring during tumor growth that are not distinguishable by conventional methods of tumor measurement. For the orthotopic xenografts, the positive correlation between the in vivo iRFP signal from mice chests and the ex vivo green fluorescent signal from gross lung tumors and the results of the suppressed tumorigenesis by miR-16 treatment indicated that lung tumor size can be accurately quantified by the emission of NIR fluorescence. In addition, orthotopic lung tumor localization can be accurately visualized using iRFP fluorescence tomography in vivo, thus revealing the trafficking of lung tumor cells. CONCLUSIONS: We introduced a novel dual fluorescence lung cancer model that provides a non-invasive option for preclinical research via the use of NIR fluorescence in live imaging of lung. PMID- 27197536 TI - Weighing up the pros and cons of immune checkpoint inhibitors in the treatment of melanoma. PMID- 27197537 TI - Are there, or shall we discover, biomarkers to guide PD-1 inhibition? AB - Paolo A Ascierto and Ramon A de Mello speak to Ellen Clarke, Commissioning Editor Despite the recent success of PD-1/PD-L1-directed immunotherapy in a number of different malignancies, there are currently no effective biomarkers available to predict patient response to treatment. This question is particularly important because these immunotherapy agents are expensive and have significant toxicity profiles. Early data are emerging on biomarkers such as PD-L1 expression; however, it is clear that further studies are needed to identify alternative biomarkers and to improve understanding of the host immune system and tumor microenvironment. In a panel interview Paolo Ascierto and Ramon de Mello discuss this important clinical question. PMID- 27197538 TI - Checkpoint inhibition for colorectal cancer: progress and possibilities. AB - Colorectal cancer (CRC) remains the third most common cause of cancer death in the USA. Despite an increase in the repertoire of treatment options available for CRC, median overall survival has plateaued at approximately 2.5 years. Strategies that engage the patient's native immune system to overcome checkpoint inhibition have proven to be promising in subsets of CRCs, specifically those with mismatch repair deficiency. Further studies are required to determine combinations of standard therapies with immunotherapy drugs and to discover the best biomarkers to predict response. This review provides insight into the progress made in treating patients with advanced CRC with immunotherapeutics and the areas that demand further research to make these drugs more effective in this patient population. PMID- 27197540 TI - Checkpoint inhibition in meningiomas. AB - Meningiomas are increasingly appreciated to share similar features with other intra-axial central nervous system neoplasms as well as systemic cancers. Immune checkpoint inhibition has emerged as a promising therapy in a number of cancers, with durable responses of years in a subset of patients. Several lines of evidence support a role for immune-based therapeutic strategies in the management of meningiomas, especially high-grade subtypes. Meningiomas frequently originate juxtaposed to venous sinuses, where an anatomic conduit for lymphatic drainage resides. Multiple populations of immune cells have been observed in meningiomas. PD-1/PD-L1 mediated immunosuppression has been implicated in high-grade meningiomas, with association between PD-L1 expression with negative prognostic outcome. These data point to the promise of future combinatorial therapeutic strategies in meningioma. PMID- 27197541 TI - PD-1 and PD-L1 inhibitors in melanoma treatment: past success, present application and future challenges. AB - Anti-programmed death (PD)-1 antibodies have now become the standard of care for advanced melanoma, with two drugs gaining US FDA approval in recent years: nivolumab and pembrolizumab. Both have demonstrated significant activity and durable response with a manageable toxicity profile. Despite initial success, ongoing challenges include patient selection and predictors of response, innate resistance and optimizing combination strategies. In this overview, we take a closer look at the history and development of therapeutic targets to the PD-1/PD ligand (L)1 pathway, clinical evidence, availability of biomarkers and their limitations in clinical practice and future strategies to improve treatment outcomes. PMID- 27197542 TI - Targeting PD-L1 for non-small-cell lung cancer. AB - Lung cancer is the leading cause of cancer-related death worldwide. For decades, cytotoxic chemotherapy has been the mainstay of treatment for the majority of patients, yet median survival remains poor and side effects from chemotherapy are not trivial. Immune checkpoint inhibitors, which exert antitumor effects by inhibiting negative T-cell regulators, are changing the landscape of treatment options for patients with non-small-cell lung cancer (NSCLC). The anti-PD-1 antibodies nivolumab and pembrolizumab are approved by the US FDA for treatment of patients with NSCLC and other tumor types. Additional agents are in clinical development. This review provides an update on the PD-1 and PD-L1 immune checkpoint inhibitors currently being evaluated in NSCLC patients. PMID- 27197539 TI - Epigenetic modifiers in immunotherapy: a focus on checkpoint inhibitors. AB - Immune surveillance should be directed to suppress tumor development and progression, involving a balance of coinhibitory and costimulatory signals that amplify immune response without overwhelming the host. Immunotherapy confers durable clinical benefit in 'immunogenic tumors', whereas in other tumors the responses are modest. Thus, immune checkpoint inhibitors may need to be combined with strategies to boost immune response or increase the tumor immune profile. Epigenetic aberrations contribute significantly to carcinogenesis. Recent findings suggest that epigenetic drugs prime the immune response by increasing expression of tumor-associated antigens and immune-related genes, as well as modulating chemokines and cytokines involved in immune system activation. This review describes our current understanding regarding epigenetic and immunotherapy combination, focusing on immune response priming to checkpoint blockade. PMID- 27197543 TI - The Centrality of Events Scale in Portuguese Adolescents: Validity Evidence Based on Internal Structure and on Relations to Other Variables. AB - We explored the measurement model of the adolescent version of the Centrality of Event Scale and its invariance across community ( n = 1,079; 42.8% male), referred for foster care ( n = 205; 58.0% male), and detained ( n = 206 male) adolescent participants. Results indicated a three-factor measurement model, including all three functions that memories of significant life events may have, as a good fit to our data, particularly for male participants. This measurement model was invariant across boys taken from those different samples but not across gender. As for the short version of the instrument, a one-factor solution was the best fit to our data. It was invariant across boys taken from those different samples and across gender. Boys and girls expressed similar experiences, whereas community male adolescents reported the lowest impact of a meaningful event, in comparison with referred and with detained boys. These findings provide evidence on the validity of the scale for use with diverse adolescent samples, which may contribute for a better understanding of the impact that significant life events may have on the development of gender-specific and group-specific vulnerabilities. PMID- 27197544 TI - Real-Time Bioluminescence Imaging of Nitroreductase in Mouse Model. AB - Nitroreductase (NTR) is an endogenous reductase overexpressed in hypoxic tumors; however, its precise detection in living cells and animals remains a considerable challenge. Herein, we developed three reaction-based probes and a related bioluminescence assay for the real-time NTR detection. The high sensitivity and selectivity of probe 3, combined with its remarkable potential of bioluminescence imaging, affords a valuable approach for in vivo imaging of NTR in a tumor model mouse. PMID- 27197545 TI - Exploring phenotype patterns of breast cancer within somatic mutations: a modicum in the intrinsic code. AB - Triple-negative (TN) breast cancer (BC) patients have limited treatment options and poor prognosis even after extant treatments and standard chemotherapeutic regimens. Linking TN patients to clinically known phenotypes with appropriate treatments is vital. Location-specific sequence variants are expected to be useful for this purpose by identifying subgroups within a disease population. Single gene mutational signatures have been widely reported, with related phenotypes in literature. We thoroughly survey currently available mutations (and mutated genes), linked to BC phenotypes, to demonstrate their limited performance as sole predictors/biomarkers to assign phenotypes to patients. We then explore mutational combinations, as a pilot study, using The Cancer Genome Atlas Research Network mutational data of BC and three machine learning methods: association rules (limitless arity multiple procedure), decision tree and hierarchical disjoint clustering. The study results in a patient classification scheme through combinatorial mutations in Phosphatidylinositol-4,5-Bisphosphate 3-Kinase and tumor protein 53, being consistent with all three methods, implying its validity from a diverse viewpoint. However, it would warrant further research to select multi-gene signatures to identify phenotypes specifically and be clinically used routinely. PMID- 27197546 TI - Metal Doping Effect of the M-Co2P/Nitrogen-Doped Carbon Nanotubes (M = Fe, Ni, Cu) Hydrogen Evolution Hybrid Catalysts. AB - The enhancement of catalytic performance of cobalt phosphide-based catalysts for the hydrogen evolution reaction (HER) is still challenging. In this work, the doping effect of some transition metal (M = Fe, Ni, Cu) on the electrocatalytic performance of the M-Co2P/NCNTs (NCNTs, nitrogen-doped carbon nanotubes) hybrid catalysts for the HER was studied systematically. The M-Co2P/NCNTs hybrid catalysts were synthesized via a simple in situ thermal decomposition process. A series of techniques, including X-ray diffraction, X-ray photoelectron spectroscopy, inductively coupled plasma-optical emission spectrometry, transmission electron microscopy, and N2 sorption were used to characterize the as-synthesized M-Co2P/NCNTs hybrid catalysts. Electrochemical measurements showed the catalytic performance according to the following order of Fe-Co2P/NCNTs > Ni Co2P/NCNTs > Cu-Co2P/NCNTs, which can be ascribed to the difference of structure, morphology, and electronic property after doping. The doping of Fe atoms promote the growth of the [111] crystal plane, resulting in a large specific area and exposing more catalytic active sites. Meanwhile, the Fe(delta+) has the highest positive charge among all the M-Co2P/NCNTs hybrid catalysts after doping. All these changes can be used to contribute the highest electrocatalytic activity of the Fe-Co2P/NCNTs hybrid catalyst for HER. Furthermore, an optimal HER electrocatalytic activity was obtained by adjusting the doping ratio of Fe atoms. Our current research indicates that the doping of metal is also an important strategy to improve the electrocatalytic activity for the HER. PMID- 27197547 TI - Inpatient Psychiatric Care: Families' Expectations and Perceptions of Support Received From Health Professionals. AB - PURPOSE: The purpose of this paper was to identify challenges of families caring for loved ones prior to inpatient psychiatric care, understand families' perceptions of support received from psychiatric health professionals, and identify ways for professionals to support families. CONCLUSIONS: Families experienced many challenges prior to hospital admission. There was a large gap between families' expectations and perceptions of actual support received by psychiatric health professionals. PRACTICE IMPLICATIONS: Nurses are well positioned to educate, advocate, and support overburdened families. Greater knowledge of families' challenges would enable nurses to anticipate and meet their needs. PMID- 27197549 TI - The crucial importance of long-term follow-up for Ebola virus survivors. PMID- 27197548 TI - Novel Vector Design and Hexosaminidase Variant Enabling Self-Complementary Adeno Associated Virus for the Treatment of Tay-Sachs Disease. AB - GM2 gangliosidosis is a family of three genetic neurodegenerative disorders caused by the accumulation of GM2 ganglioside (GM2) in neuronal tissue. Two of these are due to the deficiency of the heterodimeric (alpha-beta), "A" isoenzyme of lysosomal beta-hexosaminidase (HexA). Mutations in the alpha-subunit (encoded by HEXA) lead to Tay-Sachs disease (TSD), whereas mutations in the beta-subunit (encoded by HEXB) lead to Sandhoff disease (SD). The third form results from a deficiency of the GM2 activator protein (GM2AP), a substrate-specific cofactor for HexA. In their infantile, acute forms, these diseases rapidly progress with mental and psychomotor deterioration resulting in death by approximately 4 years of age. After gene transfer that overexpresses one of the deficient subunits, the amount of HexA heterodimer formed would empirically be limited by the availability of the other endogenous Hex subunit. The present study used a new variant of the human HexA alpha-subunit, MU, incorporating critical sequences from the beta-subunit that produce a stable homodimer (HexM) and promote functional interactions with the GM2AP- GM2 complex. We report the design of a compact adeno-associated viral (AAV) genome using a synthetic promoter-intron combination to allow self-complementary (sc) packaging of the HEXM gene. Also, a previously published capsid mutant, AAV9.47, was used to deliver the gene to brain and spinal cord while having restricted biodistribution to the liver. The novel capsid and cassette design combination was characterized in vivo in TSD mice for its ability to efficiently transduce cells in the central nervous system when delivered intravenously in both adult and neonatal mice. This study demonstrates that the modified HexM is capable of degrading long-standing GM2 storage in mice, and it further demonstrates the potential of this novel scAAV vector design to facilitate widespread distribution of the HEXM gene or potentially other similar-sized genes to the nervous system. PMID- 27197550 TI - Schistosomiasis transmission in Europe. PMID- 27197551 TI - Outbreak of urogenital schistosomiasis in Corsica (France): an epidemiological case study. AB - BACKGROUND: Schistosomiasis is a snail-borne parasitic disease endemic in several tropical and subtropical countries. However, in the summer of 2013, an unexpected outbreak of urogenital schistosomiasis occurred in Corsica, with more than 120 local people or tourists infected. We used a multidisciplinary approach to investigate the epidemiology of urogenital schistosomiasis in Corsica, aiming to elucidate the origin of the outbreak. METHODS: We did parasitological and malacological surveys at nine potential sites of infection. With the snails found, we carried out snail-parasite compatibility experiments by exposing snails to schistosome larvae recovered from the urine of a locally infected Corsican patient. Genetic analysis of both mitochondrial (cox1) and nuclear (internal transcribed spacer) DNA data from the Schistosoma eggs or miracidia recovered from the infected patients was conducted to elucidate the epidemiology of this outbreak. FINDINGS: We identified two main infection foci along the Cavu River, with many Bulinus truncatus snails found in both locations. Of the 3544 snails recovered across all sites, none were naturally infected, but laboratory-based experimental infections confirmed their compatibility with the schistosomes isolated from patients. Molecular characterisation of 73 eggs or miracidia isolated from 12 patients showed infection with Schistosoma haematobium, S haematobium-Schistosoma bovis hybrids, and S bovis. Further sequence data analysis also showed that the Corsican schistosomes were closely related to those from Senegal in west Africa. INTERPRETATION: The freshwater swimming pools of the Cavu River harbour many B truncatus snails, which are capable of transmitting S haematobium-group schistosomes. Our molecular data suggest that the parasites were imported into Corsica by individuals infected in west Africa, specifically Senegal. Hybridisation between S haematobium and the cattle schistosome S bovis had a putative role in this outbreak, showing how easily and rapidly urogenital schistosomiasis can be introduced and spread into novel areas where Bulinus snails are endemic, and how hybridisation could increase the colonisation potential of schistosomes. Furthermore our results show the potential risk of schistosomiasis outbreaks in other European areas, warranting close monitoring and surveillance of all potential transmission foci. FUNDING: WHO, ANSES, RICET, and the Ministry of Health and Consumption. PMID- 27197553 TI - The development of the MRI linac system for online MRI-guided radiotherapy: a clinical update. PMID- 27197552 TI - Viraemia and Ebola virus secretion in survivors of Ebola virus disease in Sierra Leone: a cross-sectional cohort study. AB - BACKGROUND: In survivors of Ebola virus disease, clinical sequelae including uveitis, arthralgia, and fatigue are common and necessitate systematic follow-up. However, the infection risk to health-care providers is poorly defined. Here we report Ebola virus RT-PCR data for body site and fluid samples from a large cohort of Ebola virus survivors at clinic follow-up. METHODS: In this cross sectional cohort study, consecutive survivors of Ebola virus disease attending Kerry Town survivor clinic (Freetown, Sierra Leone), who had been discharged from the Kerry Town Ebola treatment unit, were invited to participate. We collected and tested axillary, blood, conjunctival, forehead, mouth, rectal, semen, urine, and vaginal specimens for presence of Ebola virus using RT-PCR. We regarded samples to be positive for Ebola virus disease if the cycle threshold was 40 or lower. We collected demographic data from survivors of their age, sex, time since discharge from the treatment unit, and length of acute admission in the Ebola treatment unit using anonymised standard forms. FINDINGS: Between April 2, and June 16, 2015, of 151 survivors of Ebola virus disease invited to participate, 112 (74%) provided consent. The median age of participants was 21.5 years (IQR 14 31.5) with 34 (30%) participants younger than 16 years. 50 (45%) of 112 participants were male. We tested a total of 555 specimens: 103 from the axilla, 93 from blood, 92 from conjunctiva, 54 from forehead, 105 from mouth, 17 from the rectum, one from semen, 69 from urine, and 21 from the vagina. The median time from Ebola treatment unit discharge to specimen collection was 142 days (IQR 127 159). 15 participants had a total of 74 swabs taken less than 100 days from discharge. The semen sample from one participant tested positive for Ebola virus at 114 days after discharge from the treatment unit; specimens taken from the axilla, blood, conjunctiva, forehead, mouth, rectum, and urine of the same participant tested negative. All specimens from the other 111 participants tested negative. INTERPRETATION: Patients recovering from Ebola virus disease who do not meet the case definition for acute disease pose a low infection risk to health care providers 6 weeks after clearance of viraemia. Personal protective equipment after this time might be limited to standard barrier precautions, unless contact with fluids from sanctuary sites is envisaged. FUNDING: Save the Children International, Public Health England. PMID- 27197555 TI - Comparing three stochastic search algorithms for computational protein design: Monte Carlo, replica exchange Monte Carlo, and a multistart, steepest-descent heuristic. AB - Computational protein design depends on an energy function and an algorithm to search the sequence/conformation space. We compare three stochastic search algorithms: a heuristic, Monte Carlo (MC), and a Replica Exchange Monte Carlo method (REMC). The heuristic performs a steepest-descent minimization starting from thousands of random starting points. The methods are applied to nine test proteins from three structural families, with a fixed backbone structure, a molecular mechanics energy function, and with 1, 5, 10, 20, 30, or all amino acids allowed to mutate. Results are compared to an exact, "Cost Function Network" method that identifies the global minimum energy conformation (GMEC) in favorable cases. The designed sequences accurately reproduce experimental sequences in the hydrophobic core. The heuristic and REMC agree closely and reproduce the GMEC when it is known, with a few exceptions. Plain MC performs well for most cases, occasionally departing from the GMEC by 3-4 kcal/mol. With REMC, the diversity of the sequences sampled agrees with exact enumeration where the latter is possible: up to 2 kcal/mol above the GMEC. Beyond, room temperature replicas sample sequences up to 10 kcal/mol above the GMEC, providing thermal averages and a solution to the inverse protein folding problem. (c) 2016 Wiley Periodicals, Inc. PMID- 27197556 TI - Enhancing the field emission properties of Se-doped GaN nanowires. AB - Pure and Se-doped GaN nanowires (NWs) are synthesized on Pt-coated Si(111) substrates via chemical vapor deposition. The GaN NWs exhibit a uniform density with an average diameter of 20-120 nm. The structure of the NWs is wurtzite hexagonal, and the growth direction is along [0001]. Field emission measurements show that the Se-doped GaN NWs possess a low turn-on field (2.9 V MUm(-1)) compared with the pure GaN NWs (7.0 V MUm(-1)). In addition, density functional theory calculations indicate that the donor states near the Fermi level are mainly formed through the hybridization between Se 4p and N 2p orbitals and that the Fermi level move towards the vacuum level. Consequently, the work functions of Se-doped GaN NWs are lower than those of pure GaN NWs. PMID- 27197557 TI - Legitimate intermediates of oxygen evolution on iridium oxide revealed by in situ electrochemical evanescent wave spectroscopy. AB - Understanding how the four-electron oxidation of water to dioxygen proceeds in different materials is critical to the rational design of efficient catalysts towards artificial photosynthetic systems. Here, using in situ electrochemical evanescent wave spectroscopy under oxygen-evolving conditions, we report two intermediates of iridium oxide (IrOx), which is the most active and stable catalyst characterized to date in acidic medium. The observed potential dependence of the two intermediates indicated that they were associated with different surface sites, and intermediate scavenging experiments using H2O2 provided insight into their role during catalysis. Notably, an Ir(V) species with an absorption maximum at 450 nm was found to mediate the initial two-electron oxidation of water. Inhibition of the Ir(V) species by H2O2, combined with computational modeling, indicates that the accumulation and concurrent spin-state change of the Ir(V) species is a prerequisite for efficient water oxidation by IrOx electrodes. PMID- 27197554 TI - Possible mechanisms of host resistance to Haemonchus contortus infection in sheep breeds native to the Canary Islands. AB - Haemonchus contortus appears to be the most economically important helminth parasite for small ruminant production in many regions of the world. The two sheep breeds native to the Canary Islands display distinctly different resistant phenotypes under both natural and experimental infections. Canaria Hair Breed (CHB) tends to have significantly lower worm burden and delayed and reduced egg production than the susceptible Canaria Sheep (CS). To understand molecular mechanisms underlying host resistance, we compared the abomasal mucosal transcriptome of the two breeds in response to Haemonchus infection using RNAseq technology. The transcript abundance of 711 and 50 genes were significantly impacted by infection in CHB and CS, respectively (false discovery rate <0.05) while 27 of these genes were significantly affected in both breeds. Likewise, 477 and 16 Gene Ontology (GO) terms were significantly enriched in CHB and CS, respectively (P < 1.0 * 10(-4)). A broad range of mechanisms have evolved in resistant CHB to provide protection against the parasite. Our findings suggest that readily inducible acute inflammatory responses, complement activation, accelerated cell proliferation and subsequent tissue repair, and immunity directed against parasite fecundity all contributed to the development of host resistance to parasitic infection in the resistant breed. PMID- 27197558 TI - The autophagy-related genes BbATG1 and BbATG8 have different functions in differentiation, stress resistance and virulence of mycopathogen Beauveria bassiana. AB - Autophagy-related proteins play significantly different roles in eukaryotes. In the entomopathogenic fungus Beauveria bassiana, autophagy is associated with fungal growth and development. BbATG1 (a serine/threonine protein kinase) and BbATG8 (a ubiquitin-like protein) have similar roles in autophagy, but different roles in other processes. Disruption mutants of BbATG1 and BbATG8 had impaired conidial germination under starvation stress. The mutant DeltaBbATG8 exhibited enhanced sensitivity to oxidative stress, while a DeltaBbATG1 mutant did not. BbATG1 and BbATG8 showed different roles in spore differentiation. The blastospore yield was reduced by 70% and 92% in DeltaBbATG1 and DeltaBbATG8 mutants, respectively, and the double mutant had a reduction of 95%. Conidial yield was reduced by approximately 90% and 50% in DeltaBbATG1 and DeltaBbATG8 mutants, respectively. A double mutant had a reduction similar to DeltaBbATG1. Additionally, both BbATG1 and BbATG8 affected the levels of conidial protein BbCP15p required for conidiation. The virulence of each autophagy-deficient mutant was considerably weakened as indicated in topical and intrahemocoel injection assays, and showed a greater reduction in topical infection. However, BbATG1 and BbATG8 had different effects on fungal virulence. Our data indicate that these autophagy-related proteins have different functions in fungal stress response, asexual development and virulence. PMID- 27197559 TI - Cyp2aa9 regulates haematopoietic stem cell development in zebrafish. AB - Definitive haematopoiesis occurs during the lifetime of an individual, which continuously replenishes all blood and immune cells. During embryonic development, haematopoietic stem cell (HSC) formation is tightly controlled by growth factors, signalling molecules and transcription factors. But little is known about roles of the cytochrome P450 (CYP) 2 family member in the haematopoiesis. Here we report characterization and functional studies of Cyp2aa9, a novel zebrafish Cyp2 family member. And demonstrate that the cyp2aa9 is required for the HSC formation and homeostasis. Knockdown of cyp2aa9 by antisense morpholino oligos resulted the definitive HSC development is defective and the Wnt/beta-catenin activity becomes reduced. The impaired HSC formation caused by cyp2aa9 morpholino can be rescued by administration of PGE2 through the cAMP/PKA pathway. Furthermore, the in vivo PGE2 level decreases in the cyp2aa9 morphants, and none of the PGE2 precursors is able to rescue phenotypes in the Cyp2aa9-deficient embryos. Taken together, these data indicate that Cyp2aa9 is functional in the step of PGE2 synthesis from PGH2, thus promoting Wnt activation and definitive HSC development. PMID- 27197560 TI - Reduction of dietary lysine increases free glutamate content in chicken meat and improves its taste. AB - Taste is a crucial factor of meat quality, and amino acids are important taste active components in meat. Here, the effects of dietary lysine (Lys) content on taste-active components in meat, especially free glutamate (Glu), were investigated. Twenty-eight-day-old broilers (Gallus gallus) were fed diets with graded Lys content of 90% or 100% of the recommended Lys requirement, (according to the National Research Council, ) for 10 days. Free amino acid content in meat and sensory scores of meat soup were estimated. Free Glu content, the main taste active component of meat, was significantly increased by a reduction of dietary Lys. Compared with the Lys 100% group (control), free Glu concentrations of meat were increased by 35.7% in the Lys 90% group (P < 0.05). In addition, free glycine, valine, isoleucine, leucine, histidine and threonine concentrations of meat were significantly increased in the Lys 90% group (P < 0.05). Sensory evaluation of meat soup made from the Lys 100% and 90% groups indicated different meat tastes. Sensory scores of taste intensity, umami and kokumi tastes were significantly higher in the Lys 90% group. These results suggest that a reduction of dietary lysine increased free glutamate content in meat and improved its taste. PMID- 27197562 TI - Equating spatial summation in visual field testing reveals greater loss in optic nerve disease. AB - PURPOSE: To test the hypothesis that visual field assessment in ocular disease measured with target stimuli within or close to complete spatial summation results in larger threshold elevation compared to when measured with the standard Goldmann III target size. The hypothesis predicts a greater loss will be identified in ocular disease. Additionally, we sought to develop a theoretical framework that would allow comparisons of thresholds with disease progression when using different Goldmann targets. METHODS: The Humphrey Field Analyser (HFA) 30-2 grid was used in 13 patients with early/established optic nerve disease using the current Goldmann III target size or a combination of the three smallest stimuli (target size I, II and III). We used data from control subjects at each of the visual field locations for the different target sizes to establish the number of failed points (events) for the patients with optic nerve disease, as well as global indices for mean deviation (MD) and pattern standard deviation (PSD). RESULTS: The 30-2 visual field testing using alternate target size stimuli showed that all 13 patients displayed more defects (events) compared to the standard Goldmann III target size. The median increase for events was seven additional failed points: (range 1-26). The global indices also increased when the new testing approach was used (MD -3.47 to -6.25 dB and PSD 4.32 to 6.63 dB). Spatial summation mapping showed an increase in critical area (Ac) in disease and overall increase in thresholds when smaller target stimuli were used. CONCLUSIONS: When compared to the current Goldmann III paradigm, the use of alternate sized targets within the 30-2 testing protocol revealed a greater loss in patients with optic nerve disease for both event analysis and global indices (MD and PSD). We therefore provide evidence in a clinical setting that target size is important in visual field testing. PMID- 27197561 TI - Expression of an Oncogenic BARD1 Splice Variant Impairs Homologous Recombination and Predicts Response to PARP-1 Inhibitor Therapy in Colon Cancer. AB - BRCA1-associated RING domain protein 1 (BARD1) stabilizes BRCA1 protein by forming a heterodimeric RING-RING complex, and impacts function of BRCA1, including homologous recombination (HR) repair. Although colon cancer cells usually express wild type BRCA1, presence of an oncogenic BARD1 splice variant (SV) in select cancers may render BRCA1 dysfunctional and allow cells to become sensitive to HR targeting therapies. We previously reported association of loss of full-length (FL) BARD1 with poor prognosis in colon cancer as well as expression of various BARD1 SVs with unknown function. Here we show that loss of BARD1 function through the expression of a BARD1 SV, BARD1beta, results in a more malignant phenotype with decreased RAD51 foci formation, reduced BRCA1 E3 ubiquitin ligase activity, and decreased nuclear BRCA1 protein localization. BARD1beta sensitizes colon cancer cells to poly ADP ribose polymerase 1 (PARP-1) inhibition even in a FL BRCA1 background. These results suggest that expression of BARD1beta may serve as a future biomarker to assess suitability of colon cancers for HR targeting with PARP-1 inhibitors in treatment of advanced colon cancer. PMID- 27197563 TI - Positive community responses to an arts-health program designed to tackle diabetes and kidney disease in remote Aboriginal communities in Australia: a qualitative study. AB - OBJECTIVE: The Western Desert Kidney Health Project (WDKHP) is an innovative clinical screening, arts-health and community development program, staffed by Aboriginal health workers. The WDKHP is aimed at prevention and early detection, improving the chance of better management of kidney disease among people in 10 predominantly Aboriginal communities in rural Western Australia. This paper aimed to understand community responses to the WDKHP in three of these communities. METHODS: Interviews were undertaken with 26 Aboriginal people living in three remote communities. Community responses were analysed with attention to the social organisation of participants in each community and a focus on the perspectives of key groups, identified here as 'Community Leaders', 'Homelanders', 'Refuge Seekers' and 'Dislocated'. RESULTS: Participants from all groups reported that the WDKHP was highly acceptable, and an effective means of drawing attention to the need for prevention, early detection and management of diabetes and kidney disease. The integration of Aboriginal health workers to explain the project contributed to the high rates of participation in clinical screening. CONCLUSIONS: Outreach clinical services can be an appropriate method of engaging people in remote communities in addressing diabetes and kidney disease. IMPLICATIONS: The remote community setting can act as an 'enabler' of healthy lifestyle for Aboriginal people, particularly when augmented by well designed outreach programs. PMID- 27197565 TI - Dual-emitting quantum dot/carbon nanodot-based nanoprobe for selective and sensitive detection of Fe(3+) in cells. AB - A novel dual-emitting fluorescence probe is developed for rapid and ultrasensitive detection of Fe(3+). The nanoprobe is prepared by coating CdSe semiconductor quantum dots (SQDs) onto the surface of carbon nanodot (CND) doped TiO2 microspheres. The as-prepared nanoprobe exhibits the corresponding dual emissions at 436 and 596 nm for CNDs and CdSe, respectively, under a single excitation wavelength. The blue fluorescence of the CNDs is insensitive to Fe(3+), whereas the orange emission of the CdSe SQDs is functionalized to be selectively quenched by Fe(3+). The intensity ratio of I436/I596 shows a good linear relationship with the concentration of Fe(3+) in the range of 10(-9) to 10(-5) M. The nanoprobe provides an effective platform for the reliable detection of Fe(3+) with a detection limit as low as 10 nM. Besides, this ratiometric nanosensor exhibits good selectivity for Fe(3+) over other metal ions. The results reveal that the nanoprobe could provide a sensitive sensor for rapid detection of Fe(3+) with high selectivity and sensitivity. Moreover, 293T cells are used as models to achieve a potential application as a probe for monitoring Fe(3+) in cells. Thus, these dual-emitting nanoprobes could work as an alternative to conventional fluorescence probes for biolabeling, sensing and other applications. PMID- 27197564 TI - Prevalence of reported physical health problems in people with severe or profound intellectual and motor disabilities: a cross-sectional study of medical records and care plans. AB - BACKGROUND: People with severe or profound intellectual and motor disabilities (SPIMD) experience numerous serious physical health problems and comorbidities. Knowledge regarding the prevalence of these problems is needed in order to detect and treat them at an early stage. Data concerning these problems in individuals with SPIMD are limited. Therefore, the aim of this study was to determine the prevalence of reported physical health problems in adults with SPIMD through a review of medical records and care plans. METHOD: We conducted a cross-sectional study employing data obtained from medical and support records. A sample of adults with SPIMD was recruited in eight residential care settings. Physical health problems that had occurred during the previous 12 months or were chronic were recorded. RESULTS: The records of 99 participants were included. A wide range of physical health problems were found with a mean of 12 problems per person. Very high prevalence rates (>50%) were found for constipation, visual impairment, epilepsy, spasticity, deformations, incontinence and reflux. CONCLUSIONS: The results suggest that people with SPIMD simultaneously experience numerous, serious physical health problems. The reliance on reported problems may cause an underestimation of the prevalence of health problems with less visible signs and symptoms such as osteoporosis and thyroid dysfunction. PMID- 27197566 TI - Sugar concentration in nectar: a quantitative metric of crop attractiveness for refined pollinator risk assessments. AB - Those involved with pollinator risk assessment know that agricultural crops vary in attractiveness to bees. Intuitively, this means that exposure to agricultural pesticides is likely greatest for attractive plants and lowest for unattractive plants. While crop attractiveness in the risk assessment process has been qualitatively remarked on by some authorities, absent is direction on how to refine the process with quantitative metrics of attractiveness. At a high level, attractiveness of crops to bees appears to depend on several key variables, including but not limited to: floral, olfactory, visual and tactile cues; seasonal availability; physical and behavioral characteristics of the bee; plant and nectar rewards. Notwithstanding the complexities and interactions among these variables, sugar content in nectar stands out as a suitable quantitative metric by which to refine pollinator risk assessments for attractiveness. Provided herein is a proposed way to use sugar nectar concentration to adjust the exposure parameter (with what is called a crop attractiveness factor) in the calculation of risk quotients in order to derive crop-specific tier I assessments. This Perspective is meant to invite discussion on incorporating such changes in the risk assessment process. (c) 2016 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. PMID- 27197567 TI - Developing Services for Patients with Depression or Anxiety in the Context of Long-term Physical Health Conditions and Medically Unexplained Symptoms: Evaluation of an IAPT Pathfinder Site. AB - BACKGROUND: There are national policy drivers for mental health services to demonstrate that they are effectively meeting the psychological needs of people with long-term health conditions/medically unexplained symptoms (LTC/MUS). AIMS: To evaluate the implementation of a stepped-care service delivery model within an Improving Access to Psychological Therapies (IAPT) service for patients with depression or anxiety in the context of their LTC/MUS. METHOD: A stepped-care model was designed and implemented. Clinical and organizational impacts were evaluated via analyses of LTC/MUS patient profiles, throughputs and outcomes. RESULTS: The IAPT service treated N = 844 LTC and N = 172 MUS patients, with the majority (81.81%) receiving a low intensity intervention. Dropout across the service steps was low. There were few differences between LTC and MUS outcome rates regardless of step of service, but outcomes were suppressed when compared to generic IAPT patients. CONCLUSIONS: The potential contribution of IAPT stepped care service delivery models in meeting the psychological needs of LTC/MUS patients is debated. PMID- 27197568 TI - Metabolic control of asyMYCtric division. AB - Asymmetric division in CD8 T cells produces two daughter cells expressing different levels of c-Myc with distinct metabolic profiles. Manipulating this asymmetric partitioning of c-Myc skews T cell responses and potentially allows the development of more effective vaccines and cancer immunotherapies. PMID- 27197569 TI - Adenovirus infection among allogeneic stem cell transplant recipients. AB - The human adenovirus (HAdV) infection can cause severe disease in immunocompromised patients, such as those undergoing allogeneic hematopoietic stem cell transplant (ASCT). The main objective of this study was to prospectively monitor ASCT recipients for HAdV occurrence in a reference center in Brazil, and also to correlate viral positivity, viral load, molecular variant, clinical symptoms, and patients' prognosis. From October/2012 to October/2014, blood and feces of 21 ASCT recipients were screened for HAdV by Nested-PCR. Viral loads were determined by real-time PCR. In total, 57% of the patients had at least one positive sample (serum or feces) for HAdV. Patients presented significantly higher viral load in feces when compared to serum. Positive samples were characterized as HAdVs of species HAdV-C, -D, and -F. The main clinical symptom presented by infected patients was diarrhea, and Graft-versus-host disease (GVHD) was the main intercurrence. An association was observed between HAdV-positivity and diarrhea and also between HAdV-positivity and GVHD. Results from this study may contribute to a better understanding of the HAdV infection pattern in patients submitted to ASCT. Data therein highlight the importance of including HAdV testing during all routine laboratory exams performed on ASCT patients. J. Med. Virol. 89:298-303, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27197570 TI - Halofuginone reduces the inflammatory responses of DSS-induced colitis through metabolic reprogramming. AB - Hypoxia and inflammation have been identified as the hallmarks of colitis, intertwined with metabolism. Here, we report that halofuginone (HF), an antiparasitic drug, attenuates dextran sulfate sodium (DSS)-induced colitis in mice, as represented by attenuating the disease activity index, inhibiting colonic shortening, ameliorating colonic lesions and histological signs of damage, reducing colonic myeloperoxidase activity, and suppressing the production of pro-inflammatory cytokines in colon tissue. Intriguingly, the hypoxia inducible factor 1alpha (HIF-1alpha) and tumor necrosis factor alpha were also suppressed by HF treatment in colon tissues, exhibiting a tissue-specific effect. To further reveal the metabolic signatures upon HF treatment, mass spectrometry based metabolomic analysis of the small molecular metabolites in liver, spleen and colon tissues was performed. As a result, we found that HF treatment counteracted the levels of acylcarnitines, including palmitoyl-l-carnitine, isobutyrylcarnitine, vaccenylcarnitine, and myristoylcarnitine, in colon tissues with DSS induction, but no significant change in the levels of acylcarnitines was observed in liver or spleen tissues. The metabolic signatures may indicate that incomplete fatty acid oxidation (FAO) in the colon could be restored upon HF treatment as the tissue-specific metabolic characterization. Taken together, our findings uncovered that the HF potentiated anti-inflammatory effect in DSS induced colitis in mice and its underlying mechanisms could be associated with the inhibition of HIF-1alpha and reduced levels of acylcarnitines, suggesting that both the inhibition of HIF-1alpha and the counteraction of incomplete FAO might be useful in the prevention and treatment of inflammatory bowel disease. PMID- 27197571 TI - Binding of Chromium(III) to Transferrin Could Be Involved in Detoxification of Dietary Chromium(III) Rather than Transport of an Essential Trace Element. AB - Cr(III) binding to transferrin (Tf; the main Fe(III) transport protein) has been postulated to mediate cellular uptake of Cr(III) to facilitate a purported essential role for this element. Experiments using HepG2 (human hepatoma) cells, which were chosen because of high levels of the transferrin receptor, showed that Cr(III) binding to vacant Fe(III) -binding sites of human Tf effectively blocks cellular Cr(III) uptake. Through bio-layer interferometry studies of the Tf cycle, it was found that both exclusion and efflux of Cr2 (III) Tf from cells was caused by 1) relatively low Cr2 Tf affinity to cell-surface Tf receptors compared to Fe2 Tf, and 2) disruption of metal release under endosomal conditions and post endosomal Tf dissociation from the receptor. These data support mounting evidence that Cr(III) is not essential and that Tf binding is likely to be a natural protective mechanism against the toxicity and potential genotoxicity of dietary Cr through blocking Cr(III) cellular accumulation. PMID- 27197572 TI - Prenatal diagnosis of congenital myopathies and muscular dystrophies. AB - Congenital myopathies and muscular dystrophies constitute a genetically and phenotypically heterogeneous group of rare inherited diseases characterized by muscle weakness and atrophy, motor delay and respiratory insufficiency. To date, curative care is not available for these diseases, which may severely affect both life-span and quality of life. We discuss prenatal diagnosis and genetic counseling for families at risk, as well as diagnostic possibilities in sporadic cases. PMID- 27197573 TI - Low WT1 transcript levels at diagnosis predicted poor outcomes of acute myeloid leukemia patients with t(8;21) who received chemotherapy or allogeneic hematopoietic stem cell transplantation. AB - BACKGROUND: Acute myeloid leukemia (AML) with t(8;21) is a heterogeneous disease. Identifying AML patients with t(8;21) who have a poor prognosis despite achieving remission is important for determining the best subsequent therapy. This study aimed to evaluate the impact of Wilm tumor gene-1 (WT1) transcript levels and cellular homolog of the viral oncogene v-KIT receptor tyrosine kinase (C-KIT) mutations at diagnosis, and RUNX1-RUNX1T1 transcript levels after the second consolidation chemotherapy cycle on outcomes. METHODS: Eighty-eight AML patients with t(8;21) who received chemotherapy only or allogeneic hematopoietic stem cell transplantation (allo-HSCT) were included. Patients who achieved remission, received two or more cycles of consolidation chemotherapy, and had a positive measureable residual disease (MRD) test result (defined as <3-log reduction in RUNX1-RUNX1T1 transcript levels compared to baseline) after 2-8 cycles of consolidation chemotherapy were recommended to receive allo-HSCT. Patients who had a negative MRD test result were recommended to receive further chemotherapy up to only 8 cycles. WT1 transcript levels and C-KIT mutations at diagnosis, and RUNX1-RUNX1T1 transcript levels after the second consolidation chemotherapy cycle were tested. RESULTS: Patients who had a C-KIT mutation had significantly lower WT1 transcript levels than patients who did not have a C-KIT mutation (6.7% +/- 10.6% vs. 19.5% +/- 19.9%, P < 0.001). Low WT1 transcript levels (<=5.0%) but not C-KIT mutation at diagnosis, a positive MRD test result after the second cycle of consolidation chemotherapy, and receiving only chemotherapy were independently associated with high cumulative incidence of relapse in all patients (hazard ratio [HR] = 3.53, 2.30, and 11.49; 95% confidence interval [CI] 1.64-7.62, 1.82 7.56, and 4.43-29.82; P = 0.002, 0.034, and <0.001, respectively); these conditions were also independently associated with low leukemia-free survival (HR = 3.71, 2.33, and 5.85; 95% CI 1.82-7.56, 1.17-4.64, and 2.75-12.44; P < 0.001, 0.016, and <0.001, respectively) and overall survival (HR = 3.50, 2.32, and 4.34; 95% CI 1.56-7.82, 1.09-4.97, and 1.98-9.53; P = 0.002, 0.030, and <0.001, respectively) in all patients. CONCLUSIONS: Testing for WT1 transcript levels at diagnosis in patients with AML and t(8;21) may predict outcomes in those who achieve remission. A randomized study is warranted to determine whether allo-HSCT can improve prognosis in these patients. PMID- 27197575 TI - Lactating Adenoma of the Breast. AB - Lactating adenoma is an uncommon breast palpable lesion occurring in pregnancy or lactation. Although it is a benign condition, it often requires core biopsy or even surgery to exclude malignancy. As with other solid lesions in pregnancy and lactation, lactating adenoma needs an accurate evaluation in order to ensure its benign nature. Work-up must include both imaging and histologic findings. Ultrasound evaluation remains the first step in assessing the features of the lesion. Some authors consider magnetic resonance imaging as a useful tool in cases of inconclusive evaluation after ultrasound and histologic exam in an attempt to avoid surgery. Most lactating adenomas resolve spontaneously, whereas others persist or even increase in size and must be removed. The authors present a case of a 35-year-old woman at 6 months postpartum with a lactating adenoma in her right breast. After surgical removal, breastfeeding was perfectly continued within the next 24 hours, which highlights the fact that breast surgery is most often compatible with breastfeeding. PMID- 27197576 TI - Breast Milk and Hair Testing to Detect Illegal Drugs, Nicotine, and Caffeine in Donors to a Human Milk Bank. AB - BACKGROUND: The use of illegal drugs and tobacco is an exclusion criteria for accepting a nursing mother as a milk donor. The detection window for human milk testing is typically a few hours. Hair testing has been considered the gold standard to assess chronic exposure to these toxic substances. OBJECTIVE: The aim of this study was to determine the levels of illegal drugs, nicotine, and caffeine in breast milk and hair samples from donors to assess whether these substances were being used during the donation period and the months leading up to it. METHODS: Thirty-six samples of hair and breast milk were obtained from 36 donors. The tests performed identified nicotine, caffeine, morphine, cocaine, cannabis, amphetamines, codeine, methadone, and other substances derived therefrom. RESULTS: No illegal drugs were found in any of the samples analyzed. Nicotine and cotinine were found in 33.3% (12/36) of all hair samples. Among these 12 samples, 10 had cotinine concentrations consistent with cutoff values for unexposed nonsmokers, 1 had concentrations consistent with cutoff values for passive smokers, and 1 had concentrations consistent with cutoff values for active smokers. Caffeine was found in 77.7% of the hair samples and in 50% of the donor milk samples. The correlation for caffeine between donor milk and hair samples was r = 0.288, P = .0881. CONCLUSION: Donors do not use illegal drugs during either the donation period or the months leading up to it. They are occasionally exposed to tobacco smoke and almost all of them consume caffeine. PMID- 27197577 TI - Parkinson disease: Progression markers for early PD - finding the right tools for the job. PMID- 27197574 TI - The effect of acid-base clustering and ions on the growth of atmospheric nano particles. AB - The growth of freshly formed aerosol particles can be the bottleneck in their survival to cloud condensation nuclei. It is therefore crucial to understand how particles grow in the atmosphere. Insufficient experimental data has impeded a profound understanding of nano-particle growth under atmospheric conditions. Here we study nano-particle growth in the CLOUD (Cosmics Leaving OUtdoors Droplets) chamber, starting from the formation of molecular clusters. We present measured growth rates at sub-3 nm sizes with different atmospherically relevant concentrations of sulphuric acid, water, ammonia and dimethylamine. We find that atmospheric ions and small acid-base clusters, which are not generally accounted for in the measurement of sulphuric acid vapour, can participate in the growth process, leading to enhanced growth rates. The availability of compounds capable of stabilizing sulphuric acid clusters governs the magnitude of these effects and thus the exact growth mechanism. We bring these observations into a coherent framework and discuss their significance in the atmosphere. PMID- 27197579 TI - Multiple sclerosis: Real-world long-term benefits of disease-modifying MS therapy. PMID- 27197578 TI - Proton therapy for paediatric CNS tumours - improving treatment-related outcomes. AB - Radiotherapy is an integral and highly effective aspect of the management of many paediatric CNS tumours, including embryonal tumours, astrocytic tumours and ependymal tumours. Nevertheless, continued improvements in long-term survivorship of such tumours means that radiotherapy-related toxicities that affect quality of life and overall functional status for survivors are increasingly problematic, and strategies that mitigate these adverse effects are needed. One such strategy is proton therapy, which has distinct advantages over conventional photon therapy and enables greater precision in the delivery of tumoricidal radiation doses with reduced irradiation of healthy tissues. These dose distribution advantages can translate into clinical benefits by reducing the risk of long-term adverse effects of radiotherapy, such as secondary malignancy, cognitive toxicity, endocrinopathy, hearing loss and vasculopathic effects. As the availability of proton therapy increases with the development of new proton centres, this treatment modality is increasingly being used in the management of paediatric CNS tumours. In this Review, we provide an introduction to the types of paediatric CNS tumours for which proton therapy can be considered, and discuss the available evidence that proton therapy limits toxicities and improves quality of life for patients. We will also consider uncertainties surrounding the use of proton therapy, evidence for its cost-effectiveness, and its future role in the management of paediatric CNS tumours. PMID- 27197580 TI - Effectiveness of percutaneous tibial nerve stimulation in managing refractory constipation. AB - AIM: Chronic constipation can be aetiopathogenically classified into slow transit constipation (STC), rectal evacuation difficulty (RED) or a combination (BOTH). Although the efficacy of percutaneous tibial nerve stimulation (PTNS) in faecal incontinence has been well proved, a current literature search identifies only one study which assessed its effect on constipation. We aimed to evaluate the effectiveness of PTNS in patients with different causes of constipation. METHOD: Thirty-four patients [30 women, median age 50 (20-79) years] with constipation who had previously failed maximal laxative and biofeedback therapy participated in the study. All patients underwent a baseline radio-opaque marker transit study and anorectal physiology examination. All had 12 sessions of PTNS of 30 min per session. A fall in the Wexner constipation score to <=15 or by >=5 points was taken as the primary outcome. Secondary outcomes included the results of pre- and post- PTNS transit and anorectal physiology studies. RESULTS: Eleven patients had STC, 14 had RED and nine had BOTH. A response was seen in four patients (1/11 STC, 2/14 RED and 1/9 BOTH). Comparing pre- and post- PTNS, there was no significant change in the mean Wexner score (P = 0.10). There was no change in colonic transit time among the whole population (P = 0.56) or among those with STC (P = 0.47). There was no improvement in balloon expulsion in the whole group (P = 0.73) or in patients with RED (P = 0.69). CONCLUSION: PTNS is of no benefit to patients with constipation, whatever aetiopathogenic mechanism is responsible for the symptoms. PMID- 27197581 TI - High copy number of mitochondrial DNA predicts poor prognosis in patients with advanced stage colon cancer. AB - INTRODUCTION: The aim of this investigation was to determine whether alterations in mitochondrial DNA (mtDNA) copy number in colon cancer were associated with clinicopathological parameters and postsurgical outcome. METHODS: By quantitative real-time PCR assay, the mtDNA copy number was detected in a cohort of colon cancer and matched adjacent colon tissues (n = 162). RESULTS: The majority of patients had higher mtDNA content in colon cancer tissues than matched adjacent colon tissues. Moreover, high mtDNA content in tumor tissues was associated with larger tumor size, higher serum CEA level, advanced TNM stage, vascular emboli, and liver metastases. Further survival curve analysis showed that high mtDNA content was related to the worst survival in patients with colon cancer at advanced TNM stage. CONCLUSIONS: High mtDNA content is a potential effective factor of poor prognosis in patients with advanced stage colon cancer. PMID- 27197582 TI - Role of difucosylated Lewis Y antigen in outcome of locally advanced cervical squamous cell carcinoma treated with cisplatin regimen. AB - BACKGROUND: Several mechanisms are involved in the development of resistance to therapy in locally advanced cervical squamous cell carcinoma (LACSCC). Studies have shown that CD44 and Lewis Y antigen (LeY) form a complex that is associated with chemoresistance, tumor invasion and metastasis. We assessed the role of CD44 and LeY in the outcome of LACSCC patients treated with different chemotherapy regimens. METHODS: 126 LACSCC patients at FIGO stages IIB-IVA were selected from the GOCS database: 74 patients included in 3 different prospective phase II trials in the neoadjuvant setting (vinorelbine, docetaxel, ifosfamide-vinorelbine cisplatin) and 52 patients treated with standard radiochemotherapy based on cisplatin (RCBC). Clinical data at baseline, disease-free survival (DFS) and overall survival (OS) were recorded. Univariate and multivariate Cox models were employed. RESULTS: Median age was 45.6 years (range: 24.9-80.5). Sixty-three and 47 tumors were CD44+ and LeY+, respectively. Tumors with expansive growth showed higher grade (p = 0.0024), mitotic index (p = 0.0505), tumor necrosis (p = 0.0191), LeY+ (p = 0.0034) and CD44+/LeY+ coexpression (p = 0.0334). CD44+ cells were present in 91.3% of patients with local recurrence (p = 0.0317). Advanced stage was associated with LeY+ tumors. Patients treated with RCBC had worse DFS and OS when their tumors expressed LeY (p = 0.0083 and p = 0.0137, respectively). Pre-treatment hemoglobin level, FIGO stage and tumor response remained the most significant prognostic factors in Cox regression. CONCLUSIONS: In our cohort of LACSCC patients, the coexpression of CD44 and LeY was not associated with worse outcome. However, in the subgroup of patients receiving RCBC, LeY expression was correlated with shorter DFS and OS. PMID- 27197583 TI - Involvement of myeloperoxidase gene polymorphism 463G>A in development of cervical squamous cell carcinoma. AB - BACKGROUND: The myeloperoxidase (MPO) -463G>A (rs2333227) polymorphism has been linked with increased susceptibility to the development of various malignancies. However, the data on the association of the MPO -463G>A transition with cervical cancer remain inconsistent. METHODS: Using high resolution melting analysis we genotyped this polymorphism in women with cervical squamous cell carcinoma (SCC) (n = 476) and controls (n = 493) from a Polish Caucasian population. Logistic regression analysis was used to adjust for the effect of confounders such as age, parity, oral contraceptive use, tobacco smoking, and menopausal status, and revealed that the MPO -463G>A single nucleotide polymorphism (SNP) was associated with an increased risk of SCC. RESULTS: The adjusted odds ratio (OR) for patients with the A/A genotype versus G/G genotype was 0.718 (95% CI 0.531-0.972, p = 0.0316). Stratified analyses between the MPO -463G>A polymorphism and SCC risks demonstrated a protective role of the MPO -463G>A SNP in patients with a positive history of parity and negative history of tobacco smoking. In patients with a positive history of parity, the age-adjusted OR for the A/A versus G/G genotype was 0.667 (95% CI 0.479-0.929, p = 0.0164). The age-adjusted OR for patients with a negative history of tobacco smoking for the A/A versus G/G genotype was 0.491 (95% CI 0.313-0.770, p = 0.0019). CONCLUSIONS: Our study demonstrated that the MPO -463G>A SNP may protect from SCC in women from Polish Caucasian populations. PMID- 27197584 TI - Impact assessment of a maternal health project in a megacity, Nigeria: toward a future with more demand for maternal health services. AB - To improve the quantity and quality of maternal health services in Lagos State, Nigeria having a maternal mortality ratio of 555 per 100 000 live births, a four year project was implemented since February 2010. The major activity of the project was training for both the service supply and demand sides. This study aimed to examine the impact of the project on coverages and quality of the services in target areas, and guide statewide policies. The Cochran-Armitage test for trend was applied to understand trends in the service coverages during 2009 2013. The same test was performed to analyse trends in the proportions of perineal conditions (i.e. intact or tear) and to evaluate variations in midwives' snkill during 2011-2013. The paired t-test was used to analyse changes in midwives' knowledge. The project interventions contributed to a significant increase in the overall service coverages, including improvements in midwifery knowledge and possibly in their skills. However, the service coverage was still limited as of the termination of the project. To instal the interventions and maximise the effect of them state-wide, it is recommended to undertake five tasks: (i) establishment of public primary health centres offering 24-h maternal health services; (ii) redeployment and recruitment of public health personnel; (iii) expansion of midwifery trainings and continuous education by the local trainers; (iv) review of grass-roots level activities; and (v) scrutiny of barriers to maternal health services. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27197585 TI - An unusually long retrocaecal appendix. PMID- 27197586 TI - Ochronosis. PMID- 27197587 TI - When do parents and child health professionals agree on child's psychosocial problems? Cross-sectional study on parent-child health professional dyads. AB - BACKGROUND: About one third of all parents have concerns about their child's psychosocial development. Agreement between child health professionals (CHPs) and parents about such concerns may improve treatment adherence and outcomes. This study investigates which child, parenting and/or environmental stressors are associated with (dis)agreement in concerns regarding psychosocial problems in children, in parent-CHP dyads. METHODS: During routine child health assessments, data were collected from a sample of children aged 14 months to 12 years (n = 3,870). CHPs registered the psychosocial problems that they identified, and parents reported their concerns. Child psychosocial stressors were measured with the ITSEA/CBCL, and the child's history of psychosocial problems. Environmental stressors referred to stressful family/contextual situations in the past year, and parenting stressors to perceived parenting efficacy. RESULTS: The CHPs and parents disagreed on 36.4 % of the children. CHPs based their identification of problems mainly on children's history of past problem (OR = 5.85, 95% CI = 4.74 7.22). Parental concerns were most likely in case of an increased ITSEA/CBCL score (OR = 7.69, CI = 5.39-10.97). CHP-parent agreement was more likely in case of a combination of child psychosocial, parenting and environmental stressors (OR = 35.58, CI = 24.11-52.48). Parental concerns not confirmed by the CHP were associated with higher educated parents, originating from an industrialized country, and younger children. The CHP-identified problems not confirmed by parental concerns were associated with older children. CONCLUSION: Agreement between CHPs and parents is associated with a co-occurrence of child, parenting and environmental stressors. Improved agreement between CHP and parents will increase the likelihood of shared decision-making regarding follow-up care and compliance with advice. PMID- 27197589 TI - Orchidectomy attenuates high-salt diet-induced increases in blood pressure, renovascular resistance, and hind limb vascular dysfunction: role of testosterone. AB - Sex hormone-dependent vascular reactivity is an underlying factor contributing to sex differences in salt-dependent hypertension. This study evaluated the role of androgens (testosterone) in high salt-induced increase in blood pressure (BP) and altered vascular reactivity in renal blood flow and perfused hind limb preparation. Weanling male rats (8 weeks old, 180-200 g) were bilaterally orchidectomised or sham operated with or without testosterone replacement (Sustanon 250, 10 mg/kg intramuscularly once in 3 weeks) and placed on a normal (0.3%) or high (4.0%) NaCl diet for 6 weeks. The high-salt diet (HSD) increased arterial BP, renal vascular resistance (RVR) and positive fluid balance (FB). These changes were accompanied by decreased plasma nitric oxide levels. The increased BP, RVR and FB observed in the rats fed a HSD were reversed by orchidectomy while testosterone replacement prevented the reversal. Phenylephrine (PE)-induced increased vascular resistance in the perfused hind limb vascular bed was enhanced by HSD, the enhanced vascular resistance was prevented by orchidectomy and testosterone replacement reversed orchidectomy effect. Vasorelaxation responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were impaired in HSD groups, orchidectomy attenuated the impairment, while testosterone replacement prevented the orchidectomy attenuation. These data suggested that eNOS-dependent and independently-mediated pathways were equally affected by HSD in vascular function impairment and this effect is testosterone dependent in male Sprague-Dawley rats. PMID- 27197590 TI - Studies on affecting factors and mechanism of treating decentralized domestic sewage by a novel anti-clogging soil infiltration system. AB - The effects of bore diameter and particle size of polyurethane (PU) foam on soil wastewater infiltration system as well as its anti-clogging mechanism were investigated in this study. Different types of PU were used to determine the effect of bore diameter and particle size on the chemical oxygen demand (COD) removal. The results revealed that bore diameter showed little effects and the optimal size of PU should be not less than 10 mm. The formation of strong hydrophilic group on the outer layer of hydrophobic PU foam was fixed with active ingredient Al2O3, leading to good anti-clogging effect. Denaturing gradient gel electrophoresis fingerprint profiles and cluster analysis showed that the microbial community in the bottom was different from that in other places of the normal column, while it in the top has obvious differences from that in other places of the clogging column. Furthermore, the dominant microbial species of the normal column was Betaproteobacteria while Alphaproteobacteria in the clogging column. PMID- 27197588 TI - The Use of Silk as a Scaffold for Mature, Sustainable Unilocular Adipose 3D Tissue Engineered Systems. AB - There is a critical need for monitoring physiologically relevant, sustainable, human adipose tissues in vitro to gain new insights into metabolic diseases. To support long-term culture, a 3D silk scaffold assisted culture system is developed that maintains mature unilocular adipocytes ex vivo in coculture with preadipocytes, endothelial cells, and smooth muscle cells obtained from small volumes of liquefied adipose samples. Without the silk scaffold, adipose tissue explants cannot be sustained in long-term culture (3 months) due to their fragility. Adjustments to media components are used to tune lipid metabolism and proliferation, in addition to responsiveness to an inflammatory stimulus. Interestingly, patient specific responses to TNFalpha stimulation are observed, providing a proof-of-concept translational technique for patient specific disease modeling in the future. In summary, this novel 3D scaffold assisted approach is required for establishing physiologically relevant, sustainable, human adipose tissue systems from small volumes of lipoaspirate, making this methodology of great value to studies of metabolism, adipokine-driven diseases, and other diseases where the roles of adipocytes are only now becoming uncovered. PMID- 27197591 TI - Removal of polychlorinated naphthalenes by desulfurization and emissions of polychlorinated naphthalenes from sintering plant. AB - The sintering flue gas samples were collected at the inlets and outlets of the desulfurization systems to evaluate the influence of the systems on PCNs emission concentrations, profiles, and emission factors. The PCNs concentrations at the inlets and outlets were 27888-153672 pg m(-3) and 11988-42245 pg m( 3),respectively. Desulfurization systems showed excellent removal for PCNs, and the removal efficiencies of PCNs increase with increasing chlorination level. Lower chlorinated homologs are more sensitive to the desulfurization process than higher ones. High levels of PCNs were also detected in the gypsum (11600-29720 pg g(-1)) and fly ash samples (4946-64172 pg g(-1)). The annual total emissions of PCNs released to flue gas and gypsum from the sintering plants were about 394 kg, 48.5% of which was in gypsum. The surface area of the fly ash samples increased significantly from the first to the fourth stage of the series-connected electrostatic precipitator, accompanying obvious rising of concentration of PCNs in the fly ash samples. PMID- 27197593 TI - Individualized volume-corrected maximum flow rate correlates with outcome from bladder outlet surgery in men with lower urinary tract symptoms. AB - OBJECTIVES: To develop a per-patient volume correction for maximum flow rate using multiple home uroflowmetry, and to carry out a pilot study to determine the most prognostically useful volume at which to evaluate this measurement and estimate its relationship with outcome from disobstructive bladder outlet surgery. METHODS: A total of 30 men carried out home uroflowmetry using a portable device and completed symptom scores before surgery. This was repeated at least 4 months after surgery. For each man's presurgery flow data, voided volume was plotted against maximum flow rate, and a line of best fit with logarithmic form calculated. This allowed maximum flow rate to be corrected for any volume. Percentage reduction in symptom score and increase in mean maximum flow rate were correlated with volume-corrected maximum flow rates. RESULTS: Corrected maximum flow rate at all volumes showed the expected negative correlation with both outcome measures. A statistically significant correlation occurred for volumes >190 mL, with the best performance at volumes >300 mL. CONCLUSIONS: We have devised a novel method allowing estimation of maximum flow rate at any volume, which is a step forward for non-invasive diagnostics. We found this volume corrected maximum flow rate to correlate significantly with treatment outcome at sufficiently high volumes. PMID- 27197594 TI - Microfluidic Synthesis of pH-Sensitive Multicompartmental Microparticles for Multimodulated Drug Release. AB - Stimuli-responsive carriers releasing multiple drugs have been researched for synergistic combinatorial cancer treatment with reduced side-effects. However, previously used drug carriers have limitations in encapsulating multiple drug components in a single carrier and releasing each drug independently. In this work, pH-sensitive, multimodulated, anisotropic drug carrier particles are synthesized using an acid-cleavable polymer and stop-flow lithography. The particles exhibit a faster drug release rate at the acidic pH of tumors than at physiological pH, demonstrating their potential for tumor-selective drug release. The drug release rate of the particles can be adjusted by controlling the monomer composition. To accomplish multimodulated drug release, multicompartmental particles are synthesized. The drug release profile of each compartment is programmed by tailoring the monomer composition. These pH-sensitive, multicompartmental particles are promising drug carriers enabling tumor-selective and multimodulated release of multiple drugs for synergistic combination cancer therapy. PMID- 27197596 TI - Correction of the Electrical and Thermal Extrinsic Effects in Thermoelectric Measurements by the Harman Method. AB - Although the Harman method evaluates the thermoelectric figure-of-merit in a rapid and simple fashion, the accuracy of this method is affected by several electrical and thermal extrinsic factors that have not been thoroughly investigated. Here, we study the relevant extrinsic effects and a correction scheme for them. A finite element model simulates the electrical potential and temperature fields of a sample, and enables the detailed analysis of electrical and thermal transport. The model predicts that the measurement strongly depends on the materials, sample geometries, and contact resistance of the electrodes. To verify the model, we measure the thermoelectric properties of Bi2-Te3 based alloys with systematically varied sample geometries and either with a point or a surface current source. By comparing the model and experimental data, we understand how the measurement conditions determine the extrinsic effects, and, furthermore, able to extract the intrinsic thermoelectric properties. A correction scheme is proposed to eliminate the associated extrinsic effects for an accurate evaluation. This work will help the Harman method be more consistent and accurate and contribute to the development of thermoelectric materials. PMID- 27197597 TI - The first UV absorption band of l-tryptophan is not due to two simultaneous orthogonal electronic transitions differing in the dipole moment. AB - Based on UV/Vis spectroscopic evidence obtained in this work, the first band in the absorption spectrum of l-tryptophan is largely due to a single electronic transition from the ground state to the (1)Lb excited state. However, emission spectra of this compound recorded at a variable temperature in ethanol, n-butanol and diethyl ether are structureless and considerably red-shifted at room temperature; also, lowering the temperature causes the emission to become structured and to undergo such a strong blue shift that it appears to be due to the (1)Lb state of the compound. Based on these findings, the formation (from the excited (1)Lb state) of the excited state responsible for the structureless, markedly red-shifted emission in l-tryptophan is strongly dependent not only on the viscosity of the medium, but also on its dipolarity. PMID- 27197595 TI - Extraocular motoneuron pools develop along a dorsoventral axis in zebrafish, Danio rerio. AB - Both spatial and temporal cues determine the fate of immature neurons. A major challenge at the interface of developmental and systems neuroscience is to relate this spatiotemporal trajectory of maturation to circuit-level functional organization. This study examined the development of two extraocular motor nuclei (nIII and nIV), structures in which a motoneuron's identity, or choice of muscle partner, defines its behavioral role. We used retro-orbital dye fills, in combination with fluorescent markers for motoneuron location and birthdate, to probe spatial and temporal organization of the oculomotor (nIII) and trochlear (nIV) nuclei in the larval zebrafish. We describe a dorsoventral organization of the four nIII motoneuron pools, in which inferior and medial rectus motoneurons occupy dorsal nIII, while inferior oblique and superior rectus motoneurons occupy distinct divisions of ventral nIII. Dorsal nIII motoneurons are, moreover, born before motoneurons of ventral nIII and nIV. The order of neurogenesis can therefore account for the dorsoventral organization of nIII and may play a primary role in determining motoneuron identity. We propose that the temporal development of extraocular motoneurons plays a key role in assembling a functional oculomotor circuit. J. Comp. Neurol. 525:65-78, 2017. (c) 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID- 27197598 TI - Correction to "Experimental Study of the Mesospheric Removal of NF3 by Neutral Meteoric Metals and Lyman-alpha Radiation". PMID- 27197600 TI - CLIPPERS features before, during and after lymphoma. PMID- 27197601 TI - Undiagnosed pulmonary tuberculosis among prisoners in Malaysia: an overlooked risk for tuberculosis in the community. AB - OBJECTIVES: To investigate the prevalence of previously undiagnosed active tuberculosis (TB) cases among prisoners in Malaysia's largest prison using an intensified TB case-finding strategy. METHODS: From October 2012 to May 2013, prisoners housed in two distinct units (HIV-negative and HIV-positive) were approached to participate in the TB screening study. Consenting prisoners submitted two sputum samples that were examined using GeneXpert MTB/RIF, smear microscopy and liquid culture. Socio-demographic and clinical information was collected and correlates of active TB, defined as having either a positive GeneXpert MTB/RIF or culture results, were assessed using regression analyses. RESULTS: Among the total of 559 prisoners, 442 (79.1%) had complete data; 28.7% were HIV-infected, 80.8% were men and the average age was 36.4 (SD 9.8) years. Overall, 34 (7.7%) had previously undiagnosed active TB, of whom 64.7% were unable to complete their TB treatment in prison due to insufficient time (<6 months) remaining in prison. Previously undiagnosed active TB was independently associated with older age groups (AOR 11.44 and 6.06 for age >= 50 and age 40-49 years, respectively) and with higher levels of immunosuppression (CD4 < 200 cells/ml) in HIV-infected prisoners (AOR 3.07, 95% CI 1.03-9.17). CONCLUSIONS: The high prevalence of previously undiagnosed active TB in this prison highlights the inadequate performance of internationally recommended case-finding strategies and suggests that passive case-finding policies should be abandoned, especially in prison settings where HIV infection is prevalent. Moreover, partnerships between criminal justice and public health treatment systems are crucial to continue TB treatment after release. PMID- 27197599 TI - NF-kappaB and androgen receptor variant 7 induce expression of SRD5A isoforms and confer 5ARI resistance. AB - BACKGROUND: Benign prostatic hyperplasia (BPH) is treated with 5alpha-reductase inhibitors (5ARI). These drugs inhibit the conversion of testosterone to dihydrotestosterone resulting in apoptosis and prostate shrinkage. Most patients initially respond to 5ARIs; however, failure is common especially in inflamed prostates, and often results in surgery. This communication examines a link between activation of NF-kappaB and increased expression of SRD5A2 as a potential mechanism by which patients fail 5ARI therapy. METHODS: Tissue was collected from "Surgical" patients, treated specifically for lower urinary tract symptoms secondary to advanced BPH; and, cancer free transition zone from "Incidental" patients treated for low grade, localized peripheral zone prostate cancer. Clinical, molecular and histopathological profiles were analyzed. Human prostatic stromal and epithelial cell lines were genetically modified to regulate NF-kappaB activity, androgen receptor (AR) full length (AR-FL), and AR variant 7 (AR-V7) expression. RESULTS: SRD5A2 is upregulated in advanced BPH. SRD5A2 was significantly associated with prostate volume determined by Transrectal Ultrasound (TRUS), and with more severe lower urinary tract symptoms (LUTS) determined by American Urological Association Symptom Score (AUASS). Synthesis of androgens was seen in cells in which NF-kappaB was activated. AR-FL and AR-V7 expression increased SRD5A2 expression while forced activation of NF-kappaB increased all three SRD5A isoforms. Knockdown of SRD5A2 in the epithelial cells resulted in significant reduction in proliferation, AR target gene expression, and response to testosterone (T). In tissue recombinants, canonical NF-kappaB activation in prostatic epithelium elevated all three SRD5A isoforms and resulted in in vivo growth under castrated conditions. CONCLUSION: Increased BPH severity in patients correlates with SRD5A2 expression. We demonstrate that NF-kappaB and AR-V7 upregulate SRD5A expression providing a mechanism to explain failure of 5ARI therapy in BPH patients. Prostate 76:1004-1018, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27197603 TI - Coping power for preschool-aged children: a pilot randomized control trial study. AB - AIM: Preschoolers with behavioural difficulties, both at clinical and sub clinical levels, are at higher risk for several negative outcomes. The current paper reports the results from a randomized clinical trial evaluating an adaptation of the Coping Power for preschool-aged children. In the present study, Coping Power is adapted as a universal prevention intervention, in which teachers deliver a curriculum that is designed to improve children's social competence and reduce problem behaviours. METHODS: Ten nursery school classes (164 children, mean age 54.40 months) from two Italian schools were randomly assigned to Coping Power or to the control group, which received the standard academic curriculum provided in Italian nursery schools. Teachers in the five intervention classes implemented weekly lessons and extension activities over a 6-month period. Teacher and parent reports of child behaviour assessments were collected at the beginning and end of the school year. At each assessment period, teachers completed the Strengths and Difficulties Questionnaire. RESULTS: The findings suggest that after exposure to Coping Power, intervention children showed lower levels of behavioural difficulties, rated both by parents and teachers. CONCLUSIONS: The results of this study are promising and can be interpreted as providing initial support for the efficacy of the preschool version of Coping Power. PMID- 27197605 TI - Chronic foot ulcer caused by Parkes Weber syndrome. PMID- 27197602 TI - Unrelated donors are associated with improved relapse-free survival compared to related donors in patients with myelodysplastic syndrome undergoing reduced intensity allogeneic stem cell transplantation. AB - Reduced intensity allogeneic stem cell transplantation (RI alloSCT) is a potentially curative treatment approach for patients with myelodysplastic syndrome (MDS). It is currently unclear if older related donors are better than younger unrelated donors for patients with MDS undergoing RI alloSCT. We retrospectively studied 53 consecutive MDS patients who underwent RI alloSCT between April 2007 and June 2014 and evaluated associations between donor type and outcomes with adjustment for significant covariates. 34 patients (median age: 64 years) and 19 patients (median age: 60 years) received allografts from unrelated and related donors, respectively. Unrelated donors were younger than related donors (median age: 32 vs. 60 years, P < 0.0001). There were no significant differences in baseline disease characteristics of patients receiving allografts from related or unrelated donors. Patients who received allografts from unrelated donors had a lower relapse risk (adjusted hazard ratio [aHR] = 0.35, P = 0.012) and improved relapse-free survival (aHR = 0.47, P = 0.018). HLA mismatched unrelated donors were associated with a higher risk of grade 2-4 acute graft versus host disease (GVHD) (HR = 4.64, P = 0.002) without an accompanying increase in the risk of non-relapse mortality (P = 0.56). Unrelated donors provided a higher mean CD8 cell dose (P = 0.014) and were associated with higher median donor T cell chimerism at day 60 (P = 0.003) and day 100 (P = 0.03). In conclusion, patients with MDS who received allografts from unrelated donors had a lower risk of relapse and improved relapse-free survival when compared to patients who received allografts from related donors. These findings should be confirmed in a prospective study. Am. J. Hematol. 91:883-887, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27197604 TI - Persistence of Plasmodium falciparum parasitemia after artemisinin combination therapy: evidence from a randomized trial in Uganda. AB - Artemisinin resistance is rapidly spreading in Southeast Asia. The efficacy of artemisinin-combination therapy (ACT) continues to be excellent across Africa. We performed parasite transcriptional profiling and genotyping on samples from an antimalarial treatment trial in Uganda. We used qRT-PCR and genotyping to characterize residual circulating parasite populations after treatment with either ACT or ACT-primaquine. Transcripts suggestive of circulating ring stage parasites were present after treatment at a prevalence of >25% until at least 14 days post initiation of treatment. Greater than 98% of all ring stage parasites were cleared within the first 3 days, but subsequently persisted at low concentrations until day 14 after treatment. Genotyping demonstrated a significant decrease in multiplicity of infection within the first 2 days in both ACT and ACT-primaquine arms. However, multiple clone infections persisted until day 14 post treatment. Our data suggest the presence of genetically diverse persisting parasite populations after ACT treatment. Although we did not demonstrate clinical treatment failures after ACT and the viability and transmissibility of persisting ring stage parasites remain to be shown, these findings are of relevance for the interpretation of parasite clearance transmission dynamics and for monitoring drug effects in Plasmodium falciparum parasites. PMID- 27197606 TI - A new method for skin grafting in murine model. AB - Skin transplantation provides an excellent potential model to investigate the immunology of allograft rejection and tolerance induction. Despite the theoretical ease of performing skin transplantation, as well as the potential of directly observing the reaction to the transplanted tissue, the poor reliability of skin transplantation in the mouse has largely precluded the use of this model. Furthermore, there is controversy regarding the most appropriate skin graft donor site due to poor success of back skin transplantation, as compared with the thinner ear or tail skin. This study demonstrates a reliable method to successfully perform skin grafts in a mouse model, as well as the clinical and histologic outcome of syngeneic grafts. A total of 287 grafts were performed (in 126 mice) utilizing donor skin from the ear, tail or back. No graft failure or postoperative mortality was observed. Comparison of this technique with two previously established protocols of skin transplantation (5.0 absorbable Suture + tissue glue technique and no-suture technique) demonstrates the significant improvement in the engraftment success of the new technique. In summary, a new technique for murine skin grafting demonstrates improved reliability across donor site locations and strains, increasing the potential for investigating interventions to alter the rejection process. PMID- 27197608 TI - Is the diagnostic yield influenced by the indication for fetal autopsy? AB - The utility of fetal autopsy to corroborate antenatal ultrasound findings and to aid genetic counseling is well known. However, the ability to identify an underlying cause for the common indications for which it is performed is not well studied. This study aimed to determine if the diagnostic yield of fetal autopsy in identifying the underlying cause is determined by the indication of the autopsy. Five groups of fetuses were defined based on the indication for the autopsy performed in 903 cases: (i) malformations, (ii) intrauterine death (IUD), (iii) cystic hygroma and hydrops fetalis, (iv) isolated abnormalities of amniotic fluid, and (v) intrauterine growth restriction (IUGR). The highest diagnostic yield was in fetuses with isolated abnormalities of amniotic fluid (77%), followed by those with IUGR (75%), with IUD (69.6%), those in group five (55.2%) and lowest (45%) in fetuses with malformations (P < 0.001). A cause was identified in 77.8% fetuses with multiple malformations compared to 37.5% with isolated malformations (P < 0.001), with chromosomal abnormalities in 31.8% versus 9.9% respectively (P < 0.001) and malformation syndromes in 42.5% versus 26.3% (P < 0.001). Placental examination provided the highest yield in IUD, IUGR, and oligohydramnios (43.1%; P < 0.003) whereas chromosomal analysis was most useful in cystic hygroma/NIHF (28.9%; P < 0.001). This information on the diagnostic yield in fetal autopsy related its common indications, can be utilized to counsel families of the utility of autopsy to establish cause and recurrence risks and thereby assist then to make an informed decision to consent for the procedure. (c) 2016 Wiley Periodicals, Inc. PMID- 27197607 TI - Chronic Migraine Responding to Intravenous Thiamine: A Report of Two Cases. AB - BACKGROUND: Migraine is a risk factor for thiamine deficiency and Wernicke's encephalopathy (WE). WE is a highly underdiagnosed condition. The misdiagnosis is associated more with early or mild WE. The interrelation between migraine and thiamine deficiency is unknown CASE REPORTS: Here, we report two female patients with chronic migraine. During examinations, we also noted clinical signs pertinent with a diagnosis of WE. Both patients had low blood thiamine level. Intravenous thiamine supplementation led to the improvement of both WE and associated headaches. DISCUSSION: Nausea, vomiting, and anorexia of migraine may lead to mild to moderate thiamine deficiency and WE. Review of the literature suggests that WE in early or subclinical form will have nonspecific symptoms that may include frequent headache, nausea, vomiting, and anorexia. So, WE in the early stage may simulate migrainous features and this will further aggravate thiamine deficiency and a vicious cycle may be formed, and that will progressively increase the chronicity of headaches and other features. Breaking of this cycle by thiamine supplementation might be a promising therapy in a subset of patients with chronic migraine. CONCLUSION: Thiamine deficiency due to nausea, vomiting and anorexia of migraine may further aggravate migraine like headaches in cyclical pattern. PMID- 27197609 TI - Morality is real, objective, and natural. AB - To make the case that morality is real, objective, and natural, it will be argued, first, that morals exist in human nature as part of our evolutionary heritage; that morality involves how we think and act toward other moral agents in terms of whether our thoughts and actions are right or wrong with regard to their survival and flourishing; and that moral progress is real, quantifiable, and the result of our improved understanding of causality in the social and moral sciences in the same manner as our understanding of causality has progressed in the physical and biological sciences. A moral starting point is the survival and flourishing of sentient beings. PMID- 27197610 TI - Non-Intubated Thoracoscopic Segmentectomy for Second Primary Lung Cancer in a Patient With Previous Contralateral Lobectomy and Emphysematous Bullae. PMID- 27197611 TI - Synthesis of Two-Dimensional CoS1.097/Nitrogen-Doped Carbon Nanocomposites Using Metal-Organic Framework Nanosheets as Precursors for Supercapacitor Application. AB - Two-dimensional (2D) metal-organic framework (MOF) nanosheets are attracting increasing research interest. Here, for the first time, we report the facile synthesis of 2D porphyrin paddlewheel framework-3 (PPF-3) MOF nanosheets with thickness of ca. 12-43 nm. Through the simultaneous sulfidation and carbonization of PPF-3 MOF nanosheets, we have prepared the 2D nanocomposite of CoS1.097 nanoparticles (NPs) and nitrogen-doped carbon, referred to as CoSNC, in which the CoS1.097 NPs with size of ca. 10 nm are embedded in the nitrogen-doped carbon matrix. As a proof-of-concept application, the obtained 2D CoSNC nanocomposite is used as an electrode material for a supercapacitor, which exhibits a specific capacitance of 360.1 F g(-1) at a current density of 1.5 A g(-1). Moreover, the composite electrode also shows high rate capability. Its specific capacitance delivered at a current density of 30.0 A g(-1) retains 56.8% of the value at 1.5 A g(-1). PMID- 27197612 TI - Surgical treatment option of the patent nasopalatine duct: a case report. AB - The nasopalatine duct (NPD) is a bilateral, epithelium-lined oronasal communication formed in the early fetal period. It connects the oral cavity with the nasal cavity within the primary palatal process. Mostly, the NPD obliterates during prenatal development and only epithelial remnants can be found after birth. A persistent NPD is therefore considered a developmental abnormality that often exists undetected without any clinical signs of discomfort. The presence of a persisting NPD, however, can be associated with pain sensation in the anterior maxilla. Differential diagnosis of the patent NPD is of importance, in order to prevent unnecessary therapy, such as endodontic treatment or tooth extractions. The present case report describes the diagnostic procedures, surgical treatment and follow-up of the patent NPD in a 53-year-old female patient suffering from maxillary pain caused by a patent NPD. PMID- 27197613 TI - Iatrogenic posterior tibial nerve division during a combined anterior ankle arthroscopy with an additional posterolateral portal. AB - Ankle arthroscopy is an important diagnostic and therapeutic technique in the management of ankle disorders. Nowadays ankle arthroscopy provides good to excellent results (up to 90%) in the treatment of certain intra-articular disorders. Due to the superficial location of ankle joint and the abundance of overlying neurovascular structures, complications reported in ankle arthroscopy are greater than those reported in other joints. We present the first reported case of a complete division of the posterior tibial nerve during an anterior ankle arthroscopy combined with an additional posterolateral portal. This was due to a poorly controlled use of the arthroscopic instruments. PMID- 27197614 TI - A case of T2 radiculopathy after anterior C5-6 fusion. AB - Thoracic radiculopathy is a rare entity. Symptomatic adjacent-segment disease after anterior cervical fusion occurs commonly in the lower cervical spine segment. We describe the clinical presentation and treatment of T2 radiculopathy after C5-6 anterior fusion. A 60-year-old man presented with the right axillary pain for 3 months. He had undergone C5-6 anterior fusion for cervical spondylosis 5 years prior. Computed tomography (CT) and magnetic resonance images showed T2-3 degenerative disease. C5-6 anterior fusion exacerbated the T2-3 segment involved in the patient's scoliotic deformity. After 2 months of conservative treatment, we decompressed the T2 foramen via T2-3 hemilaminectomy and partial facet resection. After the surgery, his symptoms disappeared. T2 radiculopathy is rare but should be considered in the differential diagnosis of chest pain. Surgeons should pay attention not only to adjacent-segment disease but also to segmental degeneration at the apex of a scoliotic deformity after cervical anterior fusion. PMID- 27197615 TI - Cross-Talk Between PCSK9 and Damaged mtDNA in Vascular Smooth Muscle Cells: Role in Apoptosis. AB - AIMS: The present study was designed to investigate a possible interaction between vascular smooth muscle cell (SMC)-derived proprotein convertase subtilisin/kexin type 9 (PCSK9) and mitochondrial DNA (mtDNA) damage. RESULTS: Treatment of cultured SMCs with the proinflammatory stimulus lipopolysaccharide (LPS) stimulated PCSK9 release and induced mtDNA damage. PCSK9 inhibition by its siRNA reduced, and its enhancement increased, mtDNA damage. Induction of mitochondria-derived reactive oxygen species (mtROS) (by rotenone, thenoyltrifluoroacetone, or antimycin A) enhanced mtDNA damage as well as PCSK9 release, suggesting a role of mtROS in PCSK9-mtDNA damage interplay. Induction of mtDNA damage (with the autophagy inhibitor, 3-methyladenine, or DNase II inhibition) enhanced PCSK9 expression, and inhibition of mtDNA damage (with the autophagy inducer, rapamycin) reduced PCSK9 expression, indicating bidirectional interplay between PCSK9 and mtDNA damage. Other studies showed that p38 MAPK is involved in PCSK9-induced mtDNA damage, and mammalian target of rapamycin activation plays a role in mtDNA damage-induced PCSK9 release. Functional impact of PCSK9-mtDNA damage cross-talk was evident in the form of SMC apoptosis, which was enhanced in cells treated with recombinant human PCSK9, but inhibited in cells treated with PCSK9 siRNA. Last, LPS administration in wild-type mice resulted in simultaneous PCSK9 release and mtDNA damage, but mtDNA damage was minimal in PCSK9-null mice given LPS. INNOVATION: Vascular SMC-derived PCSK9 induces mtDNA damage, and damaged mtDNA fragments stimulate PCSK9 release mediated, at least in part, by mtROS. CONCLUSIONS: These observations suggest positive feedback interplay between SMC-derived PCSK9 and mtDNA damage in the proinflammatory milieu involving mtROS. This interaction results in cellular injury, characterized by apoptosis-a hallmark of atherosclerosis. Antioxid. Redox Signal. 25, 997-1008. PMID- 27197616 TI - Naringin Ameliorates HIV-1 Nucleoside Reverse Transcriptase Inhibitors- Induced Mitochondrial Toxicity. AB - BACKGROUND: Mitochondrial reactive oxygen species (ROS) generation and defective oxidative phosphorylation (OXPHOS) have been proposed as possible mechanisms underlying the development of nucleoside reverse transcriptase inhibitors (NRTIs) induced mitochondrial toxicities. Available options in managing these complications have, so far, produced controversial results, thus necessitating further research into newer agents with promise. Antioxidant and free-radical scavenging effects of naringin, a plant-derived flavonoid, have previously been demonstrated. OBJECTIVE: This study was designed to investigate the effects of naringin on NRTIs-induced mitochondrial toxicity. METHODS: Wistar rats were randomly divided into Zidovudine (AZT)-only (100 mg/kg body weight BW); AZT+Naringin (100+50 mg/kg BW); AZT+Vitamin E (100+100 mg/kg BW); Stavudine (d4T) only (50 mg/kg BW); d4T+Naringin (50+50 mg/kg BW); d4T+Vitamin E (50+100 mg/kg BW) and Vehicle (3.0 mL/kg BW)-treated groups, respectively. After 56 days of oral daily dosing, rats were euthanized by halothane overdose, blood collected by cardiac puncture and livers promptly excised for further biochemical and ultrastructural analyses.

Results: AZT- or d4T-only caused significant mitochondrial dysfunction and mitochondrial ultrastructural damage compared to controls, while either naringin or vitamin E reversed indices of mitochondrial dysfunction evidenced by significantly reduced mitochondrial malondialdehyde (MDA) and blood lactate concentrations, increased liver manganese superoxide dismutase (MnSOD) activity and upregulate expression of mitochondrial-encoded subunit of electron transport chain (ETC) complex IV protein compared to AZT- or d4T-only treated rats. Furthermore, naringin or vitamin E, respectively, ameliorated mitochondrial damage observed in AZT- or d4T-only treated rats. CONCLUSION: Naringin ameliorated oxidative stress and NRTI-induced mitochondrial damage and might, therefore, be beneficial in managing toxicities and complications arising from NRTI use. PMID- 27197617 TI - Genetic diversity and antibiogram profile of diarrhoeagenic Escherichia coli pathotypes isolated from human, animal, foods and associated environmental sources. AB - INTRODUCTION: Infectious diarrhoea particularly due to pathogenic bacteria is a major health problem in developing countries, including India. Despite significant reports of diarrhoeagenic Escherichia coli (DEC) pathotypes around the globe, studies which address genetic relatedness, antibiogram profile and their correlation with respect to their isolation from different sources are sparse. The present study determines isolation and identification of DEC pathotypes from different sources, their genetic characterisation, antibiogram profile and their correlation if any. MATERIALS AND METHODS: A total of 336 samples comprising diarrhoeic stool samples from infants (n=103), young animal (n=106), foods (n=68) and associated environmental sources (n=59) were collected from Bareilly region of India. All the samples were screened by using standard microbiological methods for the detection of E. coli. The identified E. coli were then confirmed as DEC pathotypes using polymerase chain reaction-based assays. Those DEC pathotypes identified as Enteroaggregative E. coli (EAEC) were further confirmed using HEp-2 adherence assay. All the isolated DEC pathotypes were studied for their genetic diversity using pulsed-field gel electrophoresis (PFGE), and antimicrobial susceptibility testing was performed by using disc diffusion method as per Clinical Laboratory Standards Institute guidelines. RESULTS AND DISCUSSION: Of the four DEC pathotypes investigated, EAEC was found to be the predominant pathogen with an isolation rate of 16.5% from infants, 17.9% from young animals, 16.2% from foods and 3.4% from the associated environmental sources. These EAEC isolates, on further characterisation, revealed predominance of 'atypical' EAEC, with an isolation rate of 10.7% from infants, 15.1% from young animals, 16.2% from foods, and 3.4% from the associated environmental sources. On PFGE analysis, discrimination was evident within DEC pathotypes as 52 unique pulsotypes were observed for 59 recovered DEC pathotypes. However, a few EAEC isolates were found to be clonal (clusters A, B, C, D, F, G, and H) irrespective of their source of isolation, suggests sharing and/or circulation among different sources. Further, a high antibiotic resistance pattern was observed among isolated DEC pathotypes as almost 86.4% of isolates were found to be resistant against >=3 tested drugs. PMID- 27197618 TI - Mobile Phone Use Among Medical Residents: A Cross-Sectional Multicenter Survey in Saudi Arabia. AB - BACKGROUND: Mobile phones have great potential for medical education, as they allow health care providers and students to access resources efficiently at the precise time at the point-of-care to help in informed decision making. OBJECTIVE: The objective of the study was to evaluate the prevalence of mobile phone usage among medical residents and to explore their attitudes, perceptions, and the challenges they experience when using mobile phones in academic and clinical practice. METHODS: A cross-sectional survey was conducted on all 133 residents in 17 different specialties across two large academic hospitals in Riyadh, Saudi Arabia. The Web-based validated questionnaire measured mobile phone platform preferences, and their uses in general and medical practice. The perception of confidentiality and safety impact of using mobile phones for communication and accessing patient's data was also explored, alongside challenges of use and how residents learn to use their mobile phone. RESULTS: With a response rate of 101/133 (75.9%) and mean age of 27.8 (SD 3.0) years, we found that 100/101 (99.0%) of participants were mobile phone users with mean duration of use of 5.12 (SD 2.4) years, and a range from 1 to 12 years. There was no significant difference in use between male and female respondents. A negative linear correlation was found between age and use duration (P=.004). The most common operating system used by participants was the iOS platform (55/101, 54.5%), with English the most commonly used language to operate residents' mobile phones (96/100, 96.0%) despite their native language being Arabic. For communication outside medical practice, chatting applications such as WhatsApp matched phone calls as most commonly used tools (each 88/101, 87.1%). These were also the primary tools for medical communication, but used at a lower rate (each 65/101, 64.4%). In medical practice, drug (83/101, 82.2%) and medical (80/101, 79.2%) references and medical calculation applications (61/101, 60.4%) were the most commonly used. Short battery life (48/92, 52%) was the most common technical difficulty, and distraction at least on a weekly basis (54/92, 58%) was the most likely side effect of using a mobile phone in medical practice. Practically, all participants agreed with the idea of integrating medical staff mobile phones with the hospital information system. Most residents described themselves as self learners, while half learned from peers, and a quarter learned from the Internet. Only 7/101 (6.9%) had received formal training on the medical use of mobile phones. Over half of residents thought it was safe to discuss patients over their personal, nonencrypted email. CONCLUSIONS: Mobile phone use among medical residents has become almost universal in academic and clinical settings. Thus, academic and health care institutions should support proper utilization of these devices in medical training and point-of-care decision making, while continuing to protect patient confidentiality. PMID- 27197619 TI - The frequently used intraperitoneal hyponatraemia model induces hypovolaemic hyponatraemia with possible model-dependent brain sodium loss. AB - NEW FINDINGS: What is the central question of this study? The brain response to acute hyponatraemia is usually studied in rodents by intraperitoneal instillation of hypotonic fluids (i.p. model). The i.p. model is described as 'dilutional' and 'syndrome of inappropriate ADH (SIADH)', but the mechanism has not been explored systematically and might affect the brain response. Therefore, in vivo brain and muscle response were studied in pigs. What is the main finding and its importance? The i.p. model induces hypovolaemic hyponatraemia attributable to sodium redistribution, not dilution. A large reduction in brain sodium is observed, probably because of the specific mechanism causing the hyponatraemia. This is not accounted for in current understanding of the brain response to acute hyponatraemia. Hyponatraemia is common clinically, and if it develops rapidly, brain oedema evolves, and severe morbidity and even death may occur. Experimentally, acute hyponatraemia is most frequently studied in small animal models, in which the hyponatraemia is produced by intraperitoneal instillation of hypotonic fluids (i.p. model). This hyponatraemia model is described as 'dilutional' or 'syndrome of inappropriate ADH (SIADH)', but seminal studies contradict this interpretation. To confront this issue, we developed an i.p. model in a large animal (the pig) and studied water and electrolyte responses in brain, muscle, plasma and urine. We hypothesized that hyponatraemia was induced by simple water dilution, with no change in organ sodium content. Moderate hypotonic hyponatraemia was induced by a single i.v. dose of desmopressin and intraperitoneal instillation of 2.5% glucose. All animals were anaesthetized and intensively monitored. In vivo brain and muscle water was determined by magnetic resonance imaging and related to the plasma sodium concentration. Muscle water content increased less than expected as a result of pure dilution, and muscle sodium content decreased significantly (by 28%). Sodium was redistributed to the peritoneal fluid, resulting in a significantly reduced plasma volume. This shows that the i.p. model induces hypovolaemic hyponatraemia and not dilutional/SIADH hyponatraemia. Brain oedema evolved, but brain sodium content decreased significantly (by 21%). To conclude, the i.p. model induces hypovolaemic hyponatraemia attributable to sodium redistribution and not water dilution. The large reduction in brain sodium is probably attributable to the specific mechanism that causes the hyponatraemia. This is not accounted for in the current understanding of the brain response to acute hyponatraemia. PMID- 27197620 TI - Delivery of light to the skin through ablated conduits. AB - BACKGROUND AND OBJECTIVES: Non-invasive laser skin treatment modalities are generally designed to protect the epidermis by cooling and limiting the laser energy deposition in accordance with skin type. We explore a treatment modality that uses a 2,940 nm Er:YAG laser with high tissue absorption to ablate an array of channels through the epidermis and upper dermis, and then deliver laser energy from a 1,320 nm Nd:YAG laser with lower tissue absorption through the ablated channels. Treatment through ablated conduits offers a unique capability to deliver laser radiation to a deeper level in the dermis or beyond the dermis and the delivered energy to be deposited in a nearly uniform distribution. The ablated channels represent a relatively small surface and volume fraction of the epidermis and upper dermis, and heal very fast. A pilot study was performed to explore the benefits of treatments through ablated conduits for skin tightening, cellulite, and acne scarring. MATERIALS AND METHODS: A custom-built laser from Cynosure Inc. was designed to deliver to the epidermis up to 3 J/cm2 at 2,940 nm from an Er:YAG laser followed in less than 10 ms by up to 20 J/cm2 at 1,320 nm from a Nd:YAG laser. Both laser sources were delivered to the skin through a diffractive lens array. The spatial intensity modulation created by the diffractive lens array on the skin surface consisted of a low energy density background that did not damage the epidermis and a superimposed array of much higher energy density regions where the Er:YAG laser ablated the channels, and most of the 1,320 nm laser energy was delivered through the channels. Various fluence combinations of the ablative and non-ablative lasers were tested on ex vivo human skin samples to evaluate tissue effects and parameters for a clinical test. A limited clinical study was performed to evaluate tissue response and healing effects. RESULTS: Histology confirmed the presence of ablative channels through the epidermis and upper dermis as well as the absence of epidermal damage apart from the channels. Three days posttreatment there was complete skin healing with no evidence of channel ablation or coagulation in the skin biopsies. Limited clinical testing for facial treatments showed mild improvement for acne scarring and skin laxity. CONCLUSIONS: Laser skin treatment through ablated conduits can be performed safely with fast subsequent healing of the channels ablated through the skin. Further refinement of the treatment parameters and variation of the wavelength of the non-ablative laser source may bring improved treatment efficacy. Lasers Surg. Med. 49:69-77, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27197621 TI - Role of isolated limb perfusion with recombinant human tumor necrosis factor alpha and melphalan in locally advanced extremity soft tissue sarcoma. AB - The management of locally advanced extremity soft tissue sarcoma of the limbs is challenging, particularly for recurrent tumors and those adjacent to neurovascular bundles and joints. Typically, the tumors are large, below the fascia, and high-grade (T2b or stage III according to the American Joint Committee on Cancer) and thus require multimodal therapy. Treatment options must be tailored to patient and tumor characteristics. Isolated limb perfusion with recombinant human tumor necrosis factor alpha and melphalan (TNF-ILP) adds a therapeutic option to radiation therapy (RT) and systemic chemotherapy. Although the procedure is somewhat sophisticated to learn, it is a safe method and has been used now for almost 2 decades at more than 50 centers worldwide. TNF-ILP yields a high rate of complete or nearly complete pathologic tumor remission. In combination with surgical resection of the tumor remnant after isolated limb perfusion, the limb salvage rate is close to 90%. Often, patients can be spared adjuvant RT without long-term local tumor control rates being compromised. Nevertheless, TNF-ILP has never been compared with another treatment regimen in a randomized trial. This review summarizes the mode of action and standard application of TNF-ILP and focuses on a critical discussion of the role of TNF ILP in the multimodal treatment of locally advanced primary and recurrent extremity sarcoma. Cancer 2016. (c) 2016 American Cancer Society. Cancer 2016;122:2624-2632. (c) 2016 American Cancer Society. PMID- 27197622 TI - Developing points-based risk-scoring systems in the presence of competing risks. AB - Predicting the occurrence of an adverse event over time is an important issue in clinical medicine. Clinical prediction models and associated points-based risk scoring systems are popular statistical methods for summarizing the relationship between a multivariable set of patient risk factors and the risk of the occurrence of an adverse event. Points-based risk-scoring systems are popular amongst physicians as they permit a rapid assessment of patient risk without the use of computers or other electronic devices. The use of such points-based risk scoring systems facilitates evidence-based clinical decision making. There is a growing interest in cause-specific mortality and in non-fatal outcomes. However, when considering these types of outcomes, one must account for competing risks whose occurrence precludes the occurrence of the event of interest. We describe how points-based risk-scoring systems can be developed in the presence of competing events. We illustrate the application of these methods by developing risk-scoring systems for predicting cardiovascular mortality in patients hospitalized with acute myocardial infarction. Code in the R statistical programming language is provided for the implementation of the described methods. (c) 2016 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd. PMID- 27197624 TI - Long-term stability of Cu surface nanotips. AB - Sharp nanoscale tips on the metal surfaces of electrodes enhance locally applied electric fields. Strongly enhanced electric fields trigger electron field emission and atom evaporation from the apexes of nanotips. Together, these processes may explain electric discharges in the form of small local arcs observed near metal surfaces in the presence of electric fields, even in ultra high vacuum conditions. In the present work, we investigate the stability of nanoscale tips by means of computer simulations of surface diffusion processes on copper, the main material used in high-voltage electronics. We study the stability and lifetime of thin copper (Cu) surface nanotips at different temperatures in terms of diffusion processes. For this purpose we have developed a surface kinetic Monte Carlo (KMC) model where the jump processes are described by tabulated precalculated energy barriers. We show that tall surface features with high aspect ratios can be fairly stable at room temperature. However, the stability was found to depend strongly on the temperature: 13 nm nanotips with the major axes in the [Formula: see text] crystallographic directions were found to flatten down to half of the original height in less than 100 ns at temperatures close to the melting point, whereas no significant change in the height of these nanotips was observed after 10 [Formula: see text] at room temperature. Moreover, the nanotips built up along the [Formula: see text] crystallographic directions were found to be significantly more stable than those oriented in the [Formula: see text] or [Formula: see text] crystallographic directions. The proposed KMC model has been found to be well-suited for simulating atomic surface processes and was validated against molecular dynamics simulation results via the comparison of the flattening times obtained by both methods. We also note that the KMC simulations were two orders of magnitude computationally faster than the corresponding molecular dynamics calculations. PMID- 27197623 TI - Influence of deficit irrigation on strawberry (Fragaria * ananassa Duch.) fruit quality. AB - BACKGROUND: Three different irrigation regimes - upper limit of field capacity (UFC), -12 kPa); lower limit of field capacity (LFC), -33 kPa; and deficit irrigation (DI), -70 kPa) were established on silty-loam soil and monitored with tensiometers. Yield and fruit quality of 'Flamenco' and 'Eva's Delight' ever bearing strawberry cultivars were monitored. The aim of the study was to evaluate the effect of different irrigation regimes on the content of sugars, organic acids and phenolic compounds using high-performance liquid chromatography-mass spectrometry HPLC/HPLC-MS. RESULTS: Deficit irrigation significantly increased the content of sugars (from 1.1- to 1.3 fold), organic acids (from 1.1- to 1.3 fold), their ratio (from 1.1- to 1.2-fold) and the content of most identified phenolics in cv. 'Flamenco'. Conversely, higher amounts of total sugars and organic acids (1.7- to 1.8-fold) were detected in 'Eva's Delight' strawberries at UFC and LFC irrigation. Deficit irrigation generally decreased strawberry yield of cv. 'Eva's Delight'. CONCLUSION: The results suggest superior fruit quality and taste of strawberries grown under minor deficit irrigation for cv. 'Flamenco'. (c) 2016 Society of Chemical Industry. PMID- 27197625 TI - Anticoagulants: What is new and what is the standard? AB - This commentary focuses on the status of oral anticoagulants, namely, warfarin and the novel oral anticoagulants (NOACs) such as dabigatran, rivaroxaban, apixaban, and edoxaban. PMID- 27197626 TI - Primary Ewing sarcoma/primitive neuroectodermal tumor in the adrenal gland. AB - Primary Ewing sarcoma or primitive neuroectodermal tumor (PNET) of the adrenal gland is extremely rare. We report a case of Ewing sarcoma or PNET of the adrenal in a 48-year-old Chinese woman. The patient was hospitalized with left upper quadrant abdominal pain and swelling that had been present for 1 year. Computed tomography (CT) images revealed a circumscribed mass in the left adrenal region measuring 12 cm in its greatest dimension, and the mass was surgically resected. Macroscopically, the mass (13 * 10 * 8 cm3 ) in the left adrenal gland was encapsulated, soft, appearing grayish white and yellow, and with foci of cystic degeneration, necrosis, and hemorrhage on cross-sectional. Non-tumorous adrenal tissue was compressed, but identifiable at the periphery of the specimen. Histologically, compact short spindle and oval tumor cells were arranged in sheets. Tumor cells tested positive for vimentin, CD99, Bcl-2, NKX2.2, EMA, and CD117, and weakly positive for FLI-1 on immunohistochemical analysis and showed rearrangement of the EWSR1 on fluorescence in situ hybridization analysis. Post adrenalectomy, after being recurrence free for 4.5 years, the patient relapsed and a localized recurrence was detected on a follow-up CT scan. PMID- 27197627 TI - Reply. PMID- 27197628 TI - Effect of long-term ingestion of weakly oxidised flaxseed oil on biomarkers of oxidative stress in LDL-receptor knockout mice. AB - The effect of oxidised fatty acids on atherosclerosis progression is controversial. Thus, our objective was to evaluate the effect of long-term consumption of weakly oxidised PUFA from flaxseed oil on oxidative stress biomarkers of LDL-receptor(-/-) mice. To test our hypothesis, mice were separated into three groups. The first group received a high-fat diet containing fresh flaxseed oil (CONT-), the second was fed the same diet prepared using heated flaxseed oil (OXID), and the third group received the same diet containing fresh flaxseed oil and had diabetes induced by streptozotocin (CONT+). Oxidative stress, aortic parameters and non-alcoholic fatty liver disease were assessed. After 3 months, plasma lipid profile, glucose levels, body weight, energy intake and dietary intake did not differ among groups. Likewise, oxidative stress, plasma malondialdehyde (MDA), hepatic MDA expressed as nmol/mg portion (ptn) and antioxidant enzymes did not differ among the groups. Hepatic linoleic acid, alpha linolenic acid, arachidonic acid and EPA acid declined in the OXID and CONT+ groups. Aortic wall thickness, lumen and diameter increased only in the OXID group. OXID and CONT+ groups exhibited higher concentrations of MDA, expressed as MUmol/mg ptn per %PUFA, when compared with the CONT- group. Our results suggest that ingestion of oxidised flaxseed oil increases hepatic MDA concentration and is potentially pro-atherogenic. In addition, the mean MDA value observed in all groups was similar to those reported in other studies that used xenobiotics as oxidative stress inducers. Thus, the diet applied in this study represents an interesting model for further research involving antioxidants. PMID- 27197629 TI - Blood-based screening for bowel cancer may not resolve suboptimal screening participation in Australia. AB - OBJECTIVE: Emerging blood-based screening technologies for bowel cancer may improve screening participation compared to at-home stool sampling. This study assessed the impact of different screening delivery scenarios with increasing health system interactions on sampling preferences and likelihood of screening participation. METHODS: N=1,561 persons aged 45 to 74 years completed a behavioural survey measuring demographics, readiness to screen, overall collection method preference, and proposed participation in stool and blood methods across four screening scenarios differing in terms of the number of required health system interactions. RESULTS: Overall, respondents preferred a blood test (79.6%) compared to a stool test (20.4%). However, increasing health system interactions had a strong impact on the likelihood of participating in either sampling method (p<0.001). Moreover, likelihood of participating in each of the four blood-screening scenarios was significantly lower than the current at home stool sampling approach (all p<0.001). CONCLUSIONS: Blood-based screening methods require increased contact with the health system but these interactions have negative impact on screening likelihood. All blood-based scenarios showed lower screening likelihood ratings than the current at-home FIT approach. Thus, blood-based screening may not resolve suboptimal screening participation rates in Australia. PMID- 27197630 TI - Human parainfluenza virus types 1-4 in hospitalized children with acute lower respiratory infections in China. AB - Human parainfluenza viruses (HPIVs) are an important cause of acute lower respiratory tract infections (ALRTIs). HPIV-4, a newly identified virus, has been associated with severe ALRTIs recently. A total of 771 nasopharyngeal aspirate samples were collected from hospitalized children between March 2010 and February 2011. HPIVs were detected by Nest-PCR, and other known respiratory viruses were detected by RT-PCR and PCR. All amplification products were sequenced. HPIVs were detected in 151 (19.58%) patients, of whom 28 (3.63%) were positive for HPIV-4, 12(1.55%) for HPIV-1, 4 (0.51%) for HPIV-2, and 107 (13.87%) for HPIV-3. Only three were found to be co-infected with different types of HPIVs. All HPIV positive children were under 5 years of age, with the majority being less than 1 year. Only the detection rate of HPIV-3 had a significant statistical difference (chi2 = 29.648, P = 0.000) between ages. HPIV-3 and HPIV-4 were detected during the summer. Sixty (39.74%) were co-infected with other respiratory viruses, and human rhinovirus (HRV) was the most common co-infecting virus. The most frequent clinical diagnosis was bronchopneumonia, and all patients had cough; some patients who were infected with HPIV-3 and HPIV-4 had polypnea and cyanosis. No significant difference was found in clinical manifestations between those who were infected with HPIV-4 and HPIV-3. Two genotypes for HPIV-4 were prevalent, although HPIV-4a dominated. HPIV-4 is an important virus for children hospitalized with ALRTIs in China. HRV was the most common co-infecting virus. Two genotypes for HPIV-4 are prevalent, HPIV-4a dominated. J. Med. Virol. 88:2085 2091, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27197632 TI - Memory in pregnancy and post-partum: Item specific and relational encoding processes in recall and recognition. AB - It has been recently proposed that pregnant women would perform memory tasks by focusing more on item-specific processes and less on relational processing, compared to post-partum women (Mickes, Wixted, Shapiro & Scarff, ). The present cross-sectional study tested this hypothesis by directly manipulating the type of encoding employed in the study phase. Pregnant, post-partum and control women either rated the pleasantness of word meaning (which induced item-specific elaboration) or named the semantic category to which they belonged (which induced relational elaboration). Memory for the encoded words was later tested in free recall (which emphasizes relational processing) and in recognition (which emphasizes item-specific processing). In line with Mickes et al.'s () conclusions, pregnant women in the item-specific condition performed worse than post-partum women in the relational condition in free recall, but not in recognition. However, compared to the other two groups, pregnant women also exhibited lower recognition accuracy in the item-specific condition. Overall, these results confirm that pregnant women rely on relational encoding less than post-partum women, but additionally suggest that the former group might use item specific processes less efficiently than post-partum and control women. PMID- 27197633 TI - Hepatic enhancement of Gd-EOB-DTPA-enhanced 3 Tesla MR imaging: Assessing severity of liver cirrhosis. AB - PURPOSE: To evaluate the usefulness of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MR imaging in assessing the severity of cirrhosis and liver function. MATERIALS AND METHODS: This retrospective study included 120 patients who underwent Gd-EOB-DTPA-enhanced 3 Tesla (T) MR imaging (normal liver, n = 30; Child-Pugh class A, n = 30; B, n = 30; and C, n = 30). Groups were matched for underlying disease, age (+/-5 years), gender, and creatinine (+/-0.05 mg/dL). Contrast enhancement index (CEI) was calculated and compared between normal and cirrhosis groups. We analyzed the correlation between hepatic function parameters and CEI at hepatobiliary phase (HP). RESULTS: The degree and time course of hepatic enhancement significantly differed between normal and each cirrhosis group (P < 0.001). Mean CEI at HP constantly and significantly decreased as the severity of cirrhosis increased (P < 0.001). Total bilirubin (P = 0.022), albumin (P < 0.001), platelet count (P = 0.04), and Model for End Stage Liver Disease score (P = 0.01) were independent predictors of hepatic enhancement at HP. CONCLUSION: The degree of hepatic enhancement on Gd EOB-DTPA indicates the severity of cirrhosis and is correlated with hepatic function parameters. J. Magn. Reson. Imaging 2016;44:1339-1345. PMID- 27197631 TI - Autocrine-Based Selection of Drugs That Target Ion Channels from Combinatorial Venom Peptide Libraries. AB - Animal venoms represent a rich source of pharmacologically active peptides that interact with ion channels. However, a challenge to discovering drugs remains because of the slow pace at which venom peptides are discovered and refined. An efficient autocrine-based high-throughput selection system was developed to discover and refine venom peptides that target ion channels. The utility of this system was demonstrated by the discovery of novel Kv1.3 channel blockers from a natural venom peptide library that was formatted for autocrine-based selection. We also engineered a Kv1.3 blocker peptide (ShK) derived from sea anemone to generate a subtype-selective Kv1.3 blocker with a long half-life in vivo. PMID- 27197634 TI - Diversity and fluctuation in ciliate protozoan population in the rumen of cattle. AB - The purpose of this study was to investigate the diversity and fluctuation in the ciliate protozoan population in the rumen of cattle. DNA was extracted from the rumen of three ruminally cannulated, crossbred cattle and a polymerase chain reaction (PCR)-derived clone library was constructed, using a specific primer set targeting 18S ribosomal RNA genes of ciliate protozoa. DNA fragments of seven selected clones were validated for standard DNA of the protozoa-specific real time PCR assay. Furthermore, population fluctuation of ciliate protozoa and methanogens in the cattle rumen was determined by real-time PCR. A total of 60 clones were sequenced, phylogenetically analyzed, and classified into 24 operational taxonomic units (OTUs) based on a 99% similarity criterion. More than 80% sequences were phylogenetically placed in the genus Entodinium. The rest of the sequences were placed in the genus Diploplastron (5%), Dasytricha (8.3%) and Isotricha (3.3%). The results suggest that Entodinium was the dominant group in the rumen of cattle used in this study. The ciliate protozoan population showed no significant change in numbers during the monitoring period and reached a peak at 3 h after feeding. Changes in the protozoa population were lower than those of the methanogens. PMID- 27197635 TI - Dialysis catheter placement via the left internal jugular vein: risk of brachiocephalic vein perforation. AB - PURPOSE: We discuss a case of a brachiocephalic vein (BCV) perforation after Tesio(r) central venous catheter insertion. METHOD AND RESULTS: An 80-year-old patient underwent an ultrasound-guided hemodialysis (HD) catheter placement via his left internal jugular vein (IJV). One day postoperatively, the patient became hemodynamically unstable immediately after HD initiation. As a vascular event was feared, an emergency CT scan was performed demonstrating a BCV perforation. The patient underwent a sternotomy, the lines were removed and the venous laceration was closed. The patient recovered well. CONCLUSIONS: In spite of ultrasound guidance, fluoroscopy for guidewire and sheath advancement, venous blood aspiration and a normal appearing postoperative x-ray, traumatic central venous catheter placement is still possible. Tenting of the BCV wall during catheter advancement possibly caused the venous perforation. A 'how-to' for correct catheter placement via the IJV is provided and potential pitfalls during each procedural step are discussed. PMID- 27197637 TI - Spotlights on our sister journals: Chem. Asian J. 10/2016. PMID- 27197639 TI - Contents: (Adv. Mater. 20/2016). PMID- 27197638 TI - Corrigendum: Charge Transfer Through Dithieno[2,3-a:3',2'-c]phenazine: Effect of Substitution Pattern on the Optoelectronic Properties of Regioisomeric Luminophores. PMID- 27197640 TI - Metal Oxide Heterointerfaces in Hybrid Electronic Platforms. PMID- 27197641 TI - Dye-Sensitized Solar Cells: The Future of Using Earth-Abundant Elements in Counter Electrodes for Dye-Sensitized Solar Cells (Adv. Mater. 20/2016). AB - Sustainability is an important concept generating traction in the research community. To be really sustainable the full life cycle of a product needs to be carefully considered. A key aspect of this is using elements that are either readily recycled or accessible in the Earth's biosphere. Jigsawing these materials together in compounds to address our future energy needs represents a great opportunity for the current generation of researchers. On page 3802, S. Dunn and J. Briscoe summarize the performance of a selection of alternative materials to replace platinum in the counter electrodes of dye-sensitized solar cells. PMID- 27197636 TI - What is memory? The present state of the engram. AB - The mechanism of memory remains one of the great unsolved problems of biology. Grappling with the question more than a hundred years ago, the German zoologist Richard Semon formulated the concept of the engram, lasting connections in the brain that result from simultaneous "excitations", whose precise physical nature and consequences were out of reach of the biology of his day. Neuroscientists now have the knowledge and tools to tackle this question, however, and this Forum brings together leading contemporary views on the mechanisms of memory and what the engram means today. PMID- 27197643 TI - Enhanced Charge Separation through ALD-Modified Fe2 O3 /Fe2 TiO5 Nanorod Heterojunction for Photoelectrochemical Water Oxidation. AB - Hematite suffers from poor charge transport and separation properties for solar water splitting. This paper describes the design and fabrication of a 3D Fe2 O3 /Fe2 TiO5 heterojunction photoanode with improved charge separation, via a facile hydrothermal method followed by atomic layer deposition and air annealing. A highly crystallized Fe2 TiO5 phase forms with a distinct interface with the underlying Fe2 O3 core, where a 4 nm Fe2 TiO5 overlayer leads to the best photoelectrochemical performance. The favorable band offset between Fe2 O3 and Fe2 TiO5 establishes a type-II heterojunction at the Fe2 O3 /Fe2 TiO5 interface, which drives electron-hole separation effectively. The Fe2 O3 /Fe2 TiO5 composite electrode exhibits a dramatically improved photocurrent of 1.63 mA cm(-2) at 1.23 V versus reversible hydrogen electrode (RHE) under simulated 1 sun illumination (100 mW cm(-2) ), which is 3.5 times that of the bare Fe2 O3 electrode. Decorating the Fe2 O3 /Fe2 TiO5 heterojunction photoanode with earth-abundant FeNiOx cocatalyst further expedites surface reaction kinetics, leading to an onset potential of 0.8 V versus RHE with a photocurrent of 2.7 mA cm(-2) at 1.23 V and 4.6 mA cm(-2) at 1.6 V versus RHE. This sandwich photoanode shows an excellent stability for 5 h and achieves an overall Faradaic efficiency of 95% for O2 generation. This is the best performance ever reported for Fe2 O3 /Fe2 TiO5 photoanodes. PMID- 27197644 TI - One Face of Chlamydia trachomatis: The Infectious Elementary Body. AB - The lifestyle of Chlamydiae is unique: the bacteria alternate between two morphologically distinct forms, an infectious non-replicative elementary body (EB), and a replicative, non-infectious reticulate body (RB). This review focuses on recent advances in understanding the structure and function of the infectious form of the best-studied member of the phylum, the human pathogen Chlamydia trachomatis. Once considered as an inert particle of little functional capacity, the EB is now perceived as a sophisticated entity that encounters at least three different environments during each infectious cycle. We review current knowledge on its composition and morphology, and emerging metabolic activities. These features confer resistance to the extracellular environment, the ability to penetrate a host cell and ultimately enable the EB to establish a niche enabling bacterial survival and growth. The bacterial and host molecules involved in these processes are beginning to emerge. PMID- 27197645 TI - Manipulation of the Host Cell Cytoskeleton by Chlamydia. AB - Chlamydiae are obligate intracellular pathogens. They undergo a biphasic developmental cycle differentiating between the infectious but metabolically quiescent elementary body and the vegetative, but non-infectious reticulate body. Chlamydia spends a significant portion of its development in the non-infectious stage, demanding an effective strategy of manipulating the host cells to ensure its intracellular survival and replication. A common target of all Chlamydia species studied so far is the host cell cytoskeleton, with past and recent findings revealing crucial roles in invasion, inclusion maintenance, nutrient acquisition, and egress. The molecular details of how Chlamydia co-opts the cytoskeleton is becoming clearer, with bacterial factors and their corresponding host cell targets identified. PMID- 27197646 TI - Host Cell Chaperones Hsp70/Hsp90 and Peptidyl-Prolyl Cis/Trans Isomerases Are Required for the Membrane Translocation of Bacterial ADP-Ribosylating Toxins. AB - Bacterial ADP-ribosylating toxins are the causative agents for several severe human and animal diseases such as diphtheria, cholera, or enteric diseases. They display an AB-type structure: The enzymatically active A-domain attaches to the binding/translocation B-domain which then binds to a receptor on the cell surface. After receptor-mediated endocytosis, the B-domain facilitates the membrane translocation of the unfolded A-domain into the host cell cytosol. Here, the A-domain transfers an ADP-ribose moiety onto its specific substrate which leads to characteristic cellular effects and thus to severe clinical symptoms. Since the A-domain has to reach the cytosol to achieve a cytotoxic effect, the membrane translocation represents a crucial step during toxin uptake. Host cell chaperones including Hsp90 and protein-folding helper enzymes of the peptidyl prolyl cis/trans isomerase (PPIase) type facilitate this membrane translocation of the unfolded A-domain for ADP-ribosylating toxins but not for toxins with a different enzyme activity. This review summarizes the uptake mechanisms of the ADP-ribosylating clostridial binary toxins, diphtheria toxin (DT) and cholera toxin (CT), with a special focus on the interaction of these toxins with the chaperones Hsp90 and Hsp70 and PPIases of the cyclophilin and FK506-binding protein families during the membrane translocation of their ADP ribosyltransferase domains into the host cell cytosol. Moreover, the medical implications of host cell chaperones and PPIases as new drug targets for the development of novel therapeutic strategies against diseases caused by bacterial ADP-ribosylating toxins are discussed. PMID- 27197647 TI - Serial block face scanning electron microscopy and the reconstruction of plant cell membrane systems. AB - Serial block face imaging with the scanning electron microscope has been developed as an alternative to serial sectioning and transmission electron microscopy for the ultrastructural analysis of the three-dimensional organization of cells and tissues. An ultramicrotome within the microscope specimen chamber permits sectioning and imaging to a depth of many microns within resin-embedded specimens. The technology has only recently been adopted by plant microscopists and here we describe some specimen preparation procedures suitable for plant tissue, suggested microscope imaging parameters and discuss the software required for image reconstruction and analysis. PMID- 27197649 TI - Whole body MRI (WB-MRI) assessment of metastatic spread in prostate cancer: Therapeutic perspectives on targeted management of oligometastatic disease. AB - OBJECTIVES: To determine the proportion of prostate cancer (PCa) patients with oligometastatic disease (<=3 synchronous lesions) using whole body magnetic resonance imaging with diffusion-weighted imaging (WB-MRI/DWI). To determine the proportion of patients with nodal disease confined within currently accepted target areas for extended lymph node dissection (eLND) and pelvic external beam radiation therapy (EBRT). SUBJECTS AND METHODS: Two radiologists reviewed WB MRI/DWI studies in 96 consecutive newly diagnosed metastatic PCa patients; 46 patients with newly diagnosed castration naive PCa (mHNPC) and 50 patients with first appearance of metastasis during monitoring for non-metastatic castration resistant PCa (M0 to mCRPC). The distribution of metastatic deposits was assessed and the proportions of patients with oligometastatic disease and with LN metastases located within eLND and EBRT targets were determined. RESULTS: Twenty eight percent of mHNPC and 50% of mCPRC entered the metastatic disease with <=3 sites. Bone metastases (BM) were identified in 68.8% patients; 71.7% of mHNPC and 66% mCRPC patients. Most commonly involved areas were iliac bones and lumbar spine. Enlarged lymph nodes (LN) were detected in 68.7% of patients; 69.6% of mHNPC and 68.0% of mCRPC. Most commonly involved areas were para-aortic, inter aortico-cava, and external iliac areas. BM and LN were detected concomitantly in 41% of mHNPC and 34% of mCRPC. Visceral metastases were detected in 6.7%. Metastatic disease was confined to LN located within the accepted boundaries of eLND or pelvic EBRT target areas in only <=25% and <=30% of patients, respectively. CONCLUSIONS: Non-invasive mapping of metastatic landing sites in PCa using WB-MRI/DWI shows that 28% of the mHNPC patients, and 52% of the mCRPC can be classified as oligometastatic, thus challenging the concept of metastatic targeted therapy. More than two thirds of metastatic patients have LN located outside the usually recommended targets of eLND and pelvic EBRT. Prophylactic or salvage treatments of these sole areas in patients with high-risk prostate cancer may not prevent the emergence of subsequent metastases. Prostate 76:1024-1033, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27197648 TI - Advances of Intracranial Electroencephalography in Localizing the Epileptogenic Zone. AB - Intracranial electroencephalography (iEEG) provides the best precision in estimating the location and boundary of an epileptogenic zone. Analysis of iEEG in the routine EEG frequency range (0.5-70 Hz) remains the basis in clinical practice. Low-voltage fast activity is the most commonly reported ictal onset pattern in neocortical epilepsy, and low-frequency high-amplitude repetitive spiking is the most commonly reported ictal onset pattern in mesial temporal lobe epilepsy. Recent studies using wideband EEG recording have demonstrated that examining higher (80-1000 Hz) and lower (0.016-0.5 Hz) EEG frequencies can provide additional diagnostic information and help to improve the surgical outcome. In addition, novel computational techniques of iEEG signal analysis have provided new insights into the epileptic network. Here, we review some of these recent advances. Although these sophisticated and advanced techniques of iEEG analysis show promise in localizing the epileptogenic zone, their utility needs to be further validated in larger studies. PMID- 27197650 TI - When expectancies collide: Action dynamics reveal the interaction between stimulus plausibility and congruency. AB - The cognitive architecture routinely relies on expectancy mechanisms to process the plausibility of stimuli and establish their sequential congruency. In two computer mouse-tracking experiments, we use a cross-modal verification task to uncover the interaction between plausibility and congruency by examining their temporal signatures of activation competition as expressed in a computer- mouse movement decision response. In this task, participants verified the content congruency of sentence and scene pairs that varied in plausibility. The order of presentation (sentence-scene, scene-sentence) was varied between participants to uncover any differential processing. Our results show that implausible but congruent stimuli triggered less accurate and slower responses than implausible and incongruent stimuli, and were associated with more complex angular mouse trajectories independent of the order of presentation. This study provides novel evidence of a disassociation between the temporal signatures of plausibility and congruency detection on decision responses. PMID- 27197651 TI - Follow-up and programmatic outcomes of HIV-exposed infants registered in a large HIV centre in Lilongwe, Malawi: 2012-2014. AB - OBJECTIVE: To assess follow-up and programmatic outcomes of HIV-exposed infants at Martin Preuss Centre, Lilongwe, from 2012 to 2014. METHODS: Retrospective cohort study using routinely collected HIV-exposed infant data. Data were analysed using frequencies and percentages in Stata v.13. RESULTS: Of 1035 HIV exposed infants registered 2012-2014, 79% were available to be tested for HIV and 76% were HIV-tested either with DNA-PCR or rapid HIV test serology by 24 months of age. Sixty-five infants were found to be HIV-positive and 43% were started on antiretroviral therapy (ART) at different ages from 6 weeks to 24 months. Overall, 48% of HIV-exposed infants were declared lost-to-follow-up in the database. Of these, 69% were listed for tracing; of these, 78% were confirmed as lost-to-follow-up through patient charts; of these, 51% were traced; and of these, 62% were truly not in care, the remainder being wrongly classified. Commonest reasons for being truly not in care were mother/guardian unavailability to bring infants to Martin Preuss Centre, forgetting clinic appointments and transport expenses. Of these 86 patients, 36% were successfully brought back to care and 64% remained lost-to-follow-up. CONCLUSION: Loss to follow-up remains a huge challenge in the care of HIV-exposed infants. Active tracing facilitates the return of some of these infants to care. However, programmatic data documentation must be urgently improved to better follow-up and link HIV-positive children to ART. PMID- 27197652 TI - [Non-antagonistic influence of Krumeich's intrastromal corneal ring in an experimental tissue culture system]. AB - BACKGROUND: Intrastromal insertion of Krumeich's corneal ring between graft and residual host corneal tissue appears to impair preripheral, superficial and superfluous vascularization of donor corneal tissue. OBJECTIVES: The purpose of this study was to investigate the cytotoxic effects of Krumeich's ring using tissue cultures composed of primary human dermal microvascular endothelial cells from adult donors (HMVEC). MATERIALS AND METHODS: Soluble growth medium extracts of the individual components of Krumeich's ring alloy were prepared and HMVEC were exposed to these extracts in triplicate for 1 day followed by investigation with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Furthermore, HMVEC were cultured for 5 days on either Krumeich's ring or polypropylene (PP) discs coated with individual components of the Krumeich's ring alloy followed by double vital staining with fluorescein diacetate (FDA) and propidium iodide (PI). RESULTS: The MTT assays revealed that higher doses of the extracts appeared to reduce the viability of HMVEC, while highly diluted extracts of molybdenum (Mo) powder appeared to increase the metabolic activity of HMVEC. The FDA-PI staining showed only a few live HMVEC on either cobalt (Co) or Mo coated PP discs, compared to the respective titanium (Ti) and chromium (Cr) counterparts. Viable HMVEC appeared to attach to Krumeich's ring after a 5-day incubation period. CONCLUSION: The results confirm that Krumeich's ring does not exert measurable cytotoxic effects in our chosen assay system. High dilutions of medium-soluble Mo powder extracts appear to increase the metabolic activity of HMVEC. PMID- 27197653 TI - MR Imaging in non-hepatosplenic extramedullary hematopoiesis in primary myelofibrosis. PMID- 27197654 TI - Recent sediments: environmental chemistry, ecotoxicology and engineering. PMID- 27197655 TI - Chemical immobilization of Pb, Cu, and Cd by phosphate materials and calcium carbonate in contaminated soils. AB - Soil contamination with toxic metals has increasingly become a global concern over the past few decades. Phosphate and carbonate compounds are good passivation materials for Pb immobilization, while the effect of phosphate and carbonate on the immobilization of multiple heavy metals (Pb, Cu, and Cd) in contaminated soils was seldom investigated. In this study, bone meal (BM), phosphate rock (PR), oxalic acid-activated phosphate rock (APR), super phosphate (SP), and calcium carbonate (CC) were added to the contaminated soils to evaluate the effect of phosphate materials and calcium carbonate on the immobilization of Pb, Cu, and Cd. The results showed that the pH of the treated soils increased 1.3 2.7, except SP which decreased 0.5 at most. Compared to the control treatment, all phosphates and calcium carbonate added to the polluted soils increased the fraction of residual metals, and the application of APR, PR, BM, and CC significantly reduced exchangeable and carbonate-bound fraction metals. PR and APR were the most effective for the immobilization of Pb, Cu, and Cd in the soils among these materials. Moreover, the concentrations of all metals in the toxicity characteristic leaching procedure (TCLP) leachate decreased with increasing amounts of amendments, and the concentrations of Pb in the TCLP leachate for soils treated with PR and APR were below the nonhazardous regulatory limit of 5 mg L(-1) (US Environmental Protection Agency). Based on our results, phosphate rock and oxalic acid-activated phosphate rock are effective in the immobilization of multiple metals by reducing their mobility in the co-contaminated soils. PMID- 27197656 TI - Identification and biotransformation of aliphatic hydrocarbons during co composting of sewage sludge-Date Palm waste using Pyrolysis-GC/MS technique. AB - The behavior of aliphatic hydrocarbons during co-composting of sewage sludge activated with palm tree waste was studied for 6 months using Py-GC/MS. The main aliphatic compounds represented as doublet alkenes/alkanes can be classified into three groups. The first group consists of 11 alkenes (undecene, tridecene, pentadecene, hexadecene, heptadecene, octadecene, nonadecene, eicosene, uncosene, docosene, tricosene) and 15 alkanes (heptane, octane, nonane, decane, undecane, dodecane, tetradecane, pentadecane, heptadecane, octadecane, nonadecane, eicosane, uncosane, docosane, and tricosane), which remain stable during the co composting process. The stability of these compounds is related to their recalcitrance behavior. The second group consists of five alkenes (heptene, octene, nonene, decene, dodecene) and tridecane as a single alkane that decreases during co-composting. The decrease in these compounds is the combined result of their metabolism and their conversion into other compounds. The third group is constituted with tetradecene and hexadecane that increase during composting, which could be explained by accumulation of these compounds, which are released by the partial breakdown of the substrate. As a result, these molecules are incorporated or adsorbed in the structure of humic substances. PMID- 27197657 TI - Bio-optimization of the carbon-to-nitrogen ratio for efficient vermicomposting of chicken manure and waste paper using Eisenia fetida. AB - The main objective of the present study was to determine the optimum C/N ratio for converting waste paper and chicken manure to nutrient-rich manure with minimum toxicity. Six treatments of C/N ratio 20, 30, 40, 50, 60, and 70 (T1, T2, T3, T4, T5, and T6, respectively) achieved by mixing chicken manure with shredded paper were used. The study involved a composting stage for 20 days followed by vermicomposting with Eisenia fetida for 7 weeks. The results revealed that 20 days of composting considerably degraded the organic waste mixtures from all treatments and a further 7 weeks of vermiculture significantly improved the bioconversion and nutrient value of all treatments. The C/N ratio of 40 (T3) resulted in the best quality vermicompost compared to the other treatments. Earthworm biomass was highest at T3 and T4 possibly due to a greater reduction of toxic substances in these waste mixtures. The total N, total P, and total K concentrations increased with time while total carbon, C/N ratio, electrical conductivity (EC), and heavy metal content gradually decreased with time during the vermicomposting process. Scanning electron microscopy (SEM) revealed the intrastructural degradation of the chicken manure and shredded paper matrix which confirmed the extent of biodegradation of treatment mixtures as result of the composting and vermicomposting processes. Phytotoxicity evaluation of final vermicomposts using tomato (Lycopersicon esculentum), radish (Raphanus sativus), carrot (Daucus carota), and onion (Allium cepa) as test crops showed the non phytotoxicity of the vermicomposts to be in the order T3 > T4 > T2 > T1 > T5 > T6. Generally, the results indicated that the combination of composting and vermicomposting processes is a good strategy for the management of chicken manure/paper waste mixtures and that the ideal C/N ratio of the waste mixture is 40 (T3). PMID- 27197658 TI - Electrochemical wastewater treatment: influence of the type of carbon and of nitrogen on the organic load removal. AB - Boron-doped diamond (BDD) and Ti/Pt/PbO2 anodes were utilized to perform the electrodegradation of synthetic samples containing humic acid in the presence of different organic and inorganic carbon-containing and nitrogen-containing compounds. The influence of the chloride ion in the degradation process of the different synthetic samples was also assessed. The results showed that the anodic oxidation process can efficiently degrade recalcitrant compounds such as humic acid. The presence of carbonate in solution enhances the nitrogen removal, whereas it hinders the oxidation of the organic compounds. When organic nitrogen is present, it is converted to NH4+, which in turn is oxidized to nitrate and to volatile nitrogen compounds. Hydroxyl radicals are more prone to oxidize the organic nitrogen than the ammonium nitrogen. The presence of chloride enhances the organic matter and nitrogen removal rates, BDD being the anode material that yields the highest removals. PMID- 27197659 TI - A comparative study of trace metals in male and female Caspian kutum (Rutilus frisii kutum) from the southern basin of Caspian Sea. AB - This study focuses on the extent of zinc (Zn), copper (Cu), cadmium (Cd), cobalt (Co), manganese (Mn), lead (Pb), mercury (Hg), and arsenic (As) bioaccumulation in edible muscles of Caspian kutum (Rutilus frisii kutum), in both male and female sexes at Noor and Babolsar coastal regions from the southern basin of Caspian Sea. These values were compared with the WHO and the UNFAO safety standards regarding the amount of the abovementioned heavy metals in fish tissues (mg/kg ww). Results showed that the accumulation of these elements (except for Zn) was not significantly different between sexes of male and female in Babolsar coastal regions (P > 0.05). In the other hand, accumulation of Hg and As at edible muscles of Caspian kutum has significant difference between two sexes of male and female in Noor coastal regions (P < 0.05), the female had higher concentration than the male. Furthermore, it was not significantly correlated with sex and rivers in length and weight of fish (R 2 < 0.50; P > 0.05). Based on the results, the concentration of heavy metals in the studied fish tissues proved to be significantly lower than international standards (P < 0.05), so its consumption is not a threat to the health of consumers. PMID- 27197660 TI - Occurrence and change of estrogenic activity in the process of drinking water treatment and distribution. AB - From 2010 to 2012, the Yangtze River and Hanjiang River (Wuhan section) were monitored for estrogenic activities during various water level periods. Using a recombinant yeast estrogen screen (YES) assay, 54 water samples were evaluated over the course of nine sampling campaigns. The mean 17beta-estradiol equivalent (EEQ) value of raw water from the Yangtze River was 0-5.20 ng/L; and the EEQ level from the Hanjiang River was 0-3.22 ng/L. In Wuhan, drinking water treatment plants (DWTPs) using conventional treatments reduced estrogenic activities by more than 89 %. In general, water samples collected during the level period showed weaker estrogenic activities compared to those collected during the dry period. The samples collected in 2010 showed the strongest estrogenic activities of the 3-year period. The lack of correlations between estrogenic activities and selected common water quality parameters showed that estrogenic activity cannot be tied to common water quality parameters. PMID- 27197661 TI - Program Death-1 Suppresses Autoimmune Arthritis by Inhibiting Th17 Response. AB - Program death-1 (PD-1) is a co-inhibitory receptor inducibly expressed on activated T cells. PD-1 has been reported to be associated with the development of several autoimmune diseases including rheumatoid arthritis, but the precise cellular and molecular mechanisms have not been fully elucidated. To study the role of PD-1 in the pathogenesis of rheumatoid arthritis and the possible underlying mechanisms, we performed collagen-induced arthritis (CIA) in C57BL/6 mice. Here, we show that PD-1 deficiency leads to the development of severe CIA in mice. When analyzing T cells from CIA mice ex vivo, we noticed aberrant antigen-specific Th17 responses in mice lacking PD-1. This is possibly due to deregulated activation of PKC-theta and Akt. In support of this notion, treating Pdcd1 (-/-) mice with an inhibitor of PI3-kinase that is upstream of PKC-theta and Akt significantly suppressed the disease severity. Therefore, our data indicate that PD-1 dampens antigen-specific Th17 response, thus inhibiting the disease. PMID- 27197663 TI - Outbreak of IMP-producing carbapenem-resistant Enterobacter gergoviae among kidney transplant recipients. AB - OBJECTIVES: The objective of this study was to investigate a prolonged outbreak of carbapenem-resistant Enterobacter gergoviae (CREG) involving kidney transplant recipients (KTRs) between 2009 and 2014. METHODS: A case-control study was undertaken. Controls (n = 52) were selected from CREG-negative KTRs. Surveillance cultures for CREG were collected weekly. Colonization was defined as isolation of CREG from surveillance samples or from clinical specimens, with no evidence of infection. We also investigated infection control practices at the facility. RESULTS: Of 26 identified cases, 13 had had no known contact with another CREG positive patient before the first positive culture. Seven patients (27%) developed infection. The site most often colonized was the urinary tract. During the study period two clusters were identified, one in 2009 and another in 2013 14. DNA sequencing revealed blaIMP-1 in all CREG tested. No environmental or hand cultures tested positive for CREG. An audit of infection control practices detected flaws in the handling and cleaning of urinary tract devices. Multivariate analysis identified advanced age, ureteral stent use, retransplantation and male gender as risk factors for CREG acquisition. CONCLUSIONS: An outbreak among KTRs caused by an unusual species of MDR bacteria may have resulted from a common source of contamination related to urinary tract devices. PMID- 27197662 TI - The Pharmacokinetic Exposure to Fexofenadine is Volume-Dependently Reduced in Healthy Subjects Following Oral Administration With Apple Juice. AB - Pharmacokinetic exposures to fexofenadine (FEX) are reduced by apple juice (AJ); however, the relationship between the AJ volume and the degree of AJ-FEX interaction has not been understood. In this crossover study, 10 healthy subjects received single doses of FEX 60 mg with different volumes (150, 300, and 600 mL) of AJ or water (control). To identify an AJ volume lacking clinically meaningful interaction, we tested a hypothesis that the 90% confidence interval (CI) for geometric mean ratio (GMR) of FEX AUCAJ /AUCwater is contained within a biocomparability bound of 0.5-2.0, with at least one tested volume of AJ. GMR (90% CI) of AUCAJ 150mL /AUCwater , AUCAJ 300mL /AUCwater , and AUCAJ 600mL /AUCwater were 0.903 (0.752-1.085), 0.593 (0.494-0.712), and 0.385 (0.321-0.462), respectively. While a moderate to large AJ-FEX interaction is caused by a larger volumes of AJ (e.g., 300 to 600 mL), the effect of a small volume (e.g., 150 mL) appears to be not meaningful. PMID- 27197664 TI - Incentives paid to GPs to improve healthcare have no effect on mortality, study finds. PMID- 27197665 TI - The Second International Conference on Nutrition: Implications for Hidden Hunger. AB - The Second International Conference on Nutrition (ICN2) was jointly organized by the Food and Agriculture Organization of the United Nations (FAO) and the World Health Organization (WHO) and was held at the FAO Headquarters in Rome, Italy, from 19 to 21 November 2014. The ICN2 was a high-level intergovernmental meeting that focused global attention on addressing malnutrition in all its forms: undernutrition, including micronutrient deficiencies, overweight, and obesity. The ICN2 was held to specifically address the persistent and unacceptably high levels of malnutrition. Despite much progress in reducing hunger globally, 795 million people remain undernourished, over 2 billion people suffer from various micronutrient deficiencies, and an estimated 161 million children under 5 years of age are stunted, 99 million underweight, and 51 million wasted. Meanwhile, more than 600 million adults are obese. Global problems require global solutions. The ICN2 brought together national policy-makers from food, agriculture, health, education, social protection and other relevant sectors to address the complex problem of malnutrition through a multi-sectoral approach. Two outcome documents the Rome Declaration on Nutrition and the Framework for Action - were endorsed by participating governments at the Conference, committing world leaders to establishing national policies aimed at eradicating malnutrition in all its forms and transforming food systems to make nutritious diets available to all. The Rome Declaration on Nutrition is a political statement of 10 commitments for more effective and coordinated action to improve nutrition, while the Framework for Action is a voluntary technical guide of 60 recommendations for the implementation of the political commitments. This chapter provides information on the ICN2 and its outcomes as well as follow-up activities. Emphasis is placed on the Rome Declaration on Nutrition and the Framework for Action, with special focus on hidden hunger problems that have to be addressed through different interventions and a multi-sectoral approach. PMID- 27197666 TI - Hidden and Neglected: Food Poverty in the Global North - The Case of Germany. AB - Although still a powerful economy, Germany faces rising income inequality and food insecurity. Quantitative data show that nutritional poverty in Germany has become a fact, especially for social welfare recipients. This contribution gives an overview and discusses the limits of results from different data sources, such as German food surveys, and addresses how affected population groups are systematically underrepresented. To give a more thorough impression of food insecurity in Germany, the article compares nutritional consumption data from the Statistics on Income and Living Conditions/Eurostat survey for Germany, the members of the European Union 27 (EU27), and Greece. The figures for Germans with incomes below 60% of the median equivalised income who cannot afford one proper meal every second day are worse than those in the remaining EU27 member nations, and the figures for their children are not so far from the figures for crisis stricken Greece. As eating is not only about nutrition but also a means of social activity, we consider the ability to eat and drink with friends an issue of alimentary participation. The percentages of Germans who cannot afford a drink or meal with others at least once a month is very high compared to the rates of the remaining EU27 member nations and Greece. The provided quantitative figures prove that we see serious signs of food poverty in portions of Germany, despite its comparatively strong economy. Data from hundreds of qualitative interviews describing how people stricken by food insecurity try to cope with the situation complement these results. Such data are very important, as governments widely underestimate the problem and leave it to be dealt with by food banks as the only institutional solution. PMID- 27197667 TI - Curcumin Blocks Naproxen-Induced Gastric Antral Ulcerations through Inhibition of Lipid Peroxidation and Activation of Enzymatic Scavengers in Rats. AB - Curcumin is a polyphenol derived from the plant Curcuma longa, which is used for the treatment of diseases associated with oxidative stress and inflammation. The present study was undertaken to determine the protective effect of curcumin against naproxen-induced gastric antral ulcerations in rats. Different doses (10, 50, and 100 mg/kg) of curcumin or vehicle (curcumin, 0 mg/kg) were pretreated for 3 days by oral gavage, and then gastric mucosal lesions were caused by 80 mg/kg naproxen applied for 3 days. Curcumin significantly inhibited the naproxen induced gastric antral ulcer area and lipid peroxidation in a dose-dependent manner. In addition, curcumin markedly increased activities of radical scavenging enzymes, such as superoxide dismutase (SOD), catalase, and glutathione peroxidase in a dose-dependent manner. Specifically, 100 mg/kg curcumin completely protected the gastric mucosa against the loss in the enzyme, resulting in a drastic increase of activities of radical scavenging enzymes up to more than the level of untreated normal rats. Histological examination obviously showed that curcumin prevents naproxen-induced gastric antral ulceration as a result of direct protection of the gastric mucosa. These results suggest that curcumin blocks naproxen-induced gastric antral ulcerations through prevention of lipid peroxidation and activation of radical scavenging enzymes, and it may offer a potential remedy of gastric antral ulcerations. PMID- 27197668 TI - Development of a One-Step Duplex RT-PCR Method for the Simultaneous Detection of VP3/VP1 and VP1/P2B Regions of the Hepatitis A Virus. AB - The simultaneous detection and accurate identification of hepatitis A virus (HAV) is critical in food safety and epidemiological studies to prevent the spread of HAV outbreaks. Towards this goal, a one-step duplex reverse-transcription (RT) PCR method was developed targeting the VP1/P2B and VP3/VP1 regions of the HAV genome for the qualitative detection of HAV. An HAV RT-qPCR standard curve was produced for the quantification of HAV RNA. The detection limit of the duplex RT PCR method was 2.8 * 10(1) copies of HAV. The PCR products enabled HAV genotyping analysis through DNA sequencing, which can be applied for epidemiological investigations. The ability of this duplex RT-PCR method to detect HAV was evaluated with HAV-spiked samples of fresh lettuce, frozen strawberries, and oysters. The limit of detection of the one-step duplex RT-PCR for each food model was 9.4 * 10(2) copies/20 g fresh lettuce, 9.7 * 10(3) copies/20 g frozen strawberries, and 4.1 * 10(3) copies/1.5 g oysters. Use of a one-step duplex RT PCR method has advantages such as shorter time, decreased cost, and decreased labor owing to the single amplification reaction instead of four amplifications necessary for nested RT-PCR. PMID- 27197669 TI - Cochleicola gelatinilyticus gen. nov., sp. nov., Isolated from a Marine Gastropod, Reichia luteostoma. AB - A yellow, rod-shaped, non-motile, gram-negative, and strictly aerobic bacterial strain, designated LPB0005(T), was isolated from a marine gastropod, Reichia luteostoma. Here the genome sequence was determined, which comprised 3,395,737 bp with 2,962 protein-coding genes. The DNA G+C content was 36.3 mol%. The 16S rRNA gene sequence analysis indicated that the isolate represents a novel genus and species in the family Flavobacteriaceae, with relatively low sequence similarities to other closely related genera. The isolate showed chemotaxonomic properties within the range reported for the family Flavobacteriaceae, but possesses many physiological and biochemical characteristics that distinguished it from species in the closely related genera Ulvibacter, Jejudonia, and Aureitalea. Based on phylogenetic, phenotypic, and genomic analyses, strain LPB0005(T) represents a novel genus and species, for which the name Cochleicola gelatinilyticus gen. nov., sp. nov. is proposed. The type strain is LPB0005(T) (= KACC 18693(T) = JCM 31218(T)). PMID- 27197670 TI - Nematicidal Activity of Kojic Acid Produced by Aspergillus oryzae against Meloidogyne incognita. AB - The fungal strain EML-DML3PNa1 isolated from leaf of white dogwood (Cornus alba L.) showed strong nematicidal activity with juvenile mortality of 87.6% at a concentration of 20% fermentation broth filtrate at 3 days after treatment. The active fungal strain was identified as Aspergillus oryzae, which belongs to section Flavi, based on the morphological characteristics and sequence analysis of the ITS rDNA, calmodulin (CaM), and beta-tubulin (BenA) genes. The strain reduced the pH value to 5.62 after 7 days of incubation. Organic acid analysis revealed the presence of citric acid (515.0 mg/kg), malic acid (506.6 mg/kg), and fumaric acid (21.7 mg/kg). The three organic acids showed moderate nematicidal activities, but the mixture of citric acid, malic acid, and fumaric acid did not exhibit the full nematicidal activity of the culture filtrate of EML- DML3PNa1. Bioassay-guided fractionation coupled with (1)H- and (13)C-NMR and EI-MS analyses led to identification of kojic acid as the major nematicidal metabolite. Kojic acid exhibited dose-dependent mortality and inhibited the hatchability of M. incognita, showing EC50 values of 195.2 ug/ml and 238.3 ug/ml, respectively, at 72 h postexposure. These results suggest that A. oryzae EML-DML3PNa1 and kojic acid have potential as a biological control agent against M. incognita. PMID- 27197671 TI - Biosorption of Lead(II) by Arthrobacter sp. 25: Process Optimization and Mechanism. AB - In the present work, Arthrobacter sp. 25, a lead-tolerant bacterium, was assayed to remove lead(II) from aqueous solution. The biosorption process was optimized by response surface methodology (RSM) based on the Box-Behnken design. The relationships between dependent and independent variables were quantitatively determined by second-order polynomial equation and 3D response surface plots. The biosorption mechanism was explored by characterization of the biosorbent before and after biosorption using atomic force microscopy (AFM), scanning electron microscopy, energy dispersive X-ray spectroscopy, X-ray diffraction, and Fourier transform infrared spectroscopy. The results showed that the maximum adsorption capacity of 9.6 mg/g was obtained at the initial lead ion concentration of 108.79 mg/l, pH value of 5.75, and biosorbent dosage of 9.9 g/l (fresh weight), which was close to the theoretically expected value of 9.88 mg/g. Arthrobacter sp. 25 is an ellipsoidalshaped bacterium covered with extracellular polymeric substances. The biosorption mechanism involved physical adsorption and microprecipitation as well as ion exchange, and functional groups such as phosphoryl, hydroxyl, amino, amide, carbonyl, and phosphate groups played vital roles in adsorption. The results indicate that Arthrobacter sp. 25 may be potentially used as a biosorbent for low-concentration lead(II) removal from wastewater. PMID- 27197672 TI - Estrogen Receptor alpha and beta in Mouse: Adipose-Derived Stem Cell Proliferation, Migration, and Brown Adipogenesis In Vitro. AB - BACKGROUND/AIMS: Adipose-derived stem cells (ASCs) belong to mesenchymal stem cells and may play a potential role as seeding cells in stem cell transplantation. To be able to exploit stem cells as therapeutic tool, their defects in some important cellular functions, such as low survival rate and cellular activity, should be considered. This is especially the case for stem cells that are intended for transplantation. Of note, stem cell responses to hormones should be considered since estrogen is known to play a critical role in stem cell behavior. However, different impacts of the estrogen receptor (ER) types alpha and beta have not been fully determined in ASC function. In this study, we investigated effects of ERalpha and ERbeta on ASC proliferation, migration, as well as in adipogenesis. METHODS: ASCs obtained from mice were cultured with 100nM ERalpha or ERbeta agonist PPT and DPN, respectively. The ERalpha and ERbeta antagonist ICI 182,780 (100nM) was used as control. RESULTS: Compared to ERbeta, ERalpha appears more potent in improving ASC proliferation and migration. Investigation of adipogenesis revealed that ERbeta played a significant role in suppressing ASC-mediated brown tissue adipogenesis which is in contrast to ERalpha. These results correlated with reduced mRNA expression of UCP-1, PGC-1alpha and PPAR-x03B3;. CONCLUSIONS: ERalpha plays a more critical role in promoting ASC proliferation and migration while ERbeta is more potent in suppressing ASC brown adipose tissue differentiation mediated by decreased UCP-1, PGC-1alpha and PPAR-x03B3; expression. PMID- 27197673 TI - Growth Differentiation Factor 15, Its 12-Month Relative Change, and Risk of Cardiovascular Events and Total Mortality in Patients with Stable Coronary Heart Disease: 10-Year Follow-up of the KAROLA Study. AB - BACKGROUND: This study considered whether baseline concentrations and 12-month changes of growth differentiation factor 15 (GDF-15) are associated with subsequent cardiovascular events (CVEs) and total mortality in patients with stable coronary heart disease. METHODS: Baseline GDF-15 serum concentrations were measured in 1073 participants in a cardiac rehabilitation program (median follow up 10 years). GDF-15 associations with subsequent CVE and total mortality were evaluated by Cox-proportional hazards models adjusting for well-established cardiovascular risk factors (Model 2), plus N-terminal probrain natriuretic peptide, high-sensitivity (hs) CRP, and hs cardiac troponin T (Model 3). RESULTS: In our study population [84.7% men, mean age 59 years, median baseline GDF-15 1232 ng/L (interquartile range, 916, 1674)] we observed 190 CVE and 162 deaths. Compared to participants with GDF-15 <1200 ng/L, increased risk for death was found in participants with GDF-15 >=1200 and <=1800 ng/L [hazard ratio (HR) 1.68 (95% CI, 1.08-2.62)] and with GDF-15 >1800 ng/L [HR 1.73 (1.02-2.94)], even in Model 3. The 12-month relative median change was -16.7%. As compared to participants with 12-month relative changes between -20% and 20%, GDF-15 increments >20% were associated with: a) an HR of 1.84 (1.04-3.26) for CVE in Model 2, but found nonsignificant in Model 3; (b) an HR of 2.26 (1.32-3.86) for death even in Model 3. CONCLUSIONS: GDF-15 at baseline is independently associated with subsequent CVE and 10-year total mortality. Twelve-month relative changes remained associated with subsequent CVE when adjusting for well established cardiovascular risk factors, and with total mortality even after further adjustment for established cardiac biomarkers. PMID- 27197674 TI - Direct Comparison of Metastasis-Related miRNAs Expression Levels in Circulating Tumor Cells, Corresponding Plasma, and Primary Tumors of Breast Cancer Patients. AB - BACKGROUND: Circulating tumor cells (CTCs) and microRNAs (miRNAs) are important in liquid biopsies in which peripheral blood is used to characterize the evolution of solid tumors. We evaluated the expression levels of miR-21, miR 146a, miR-200c, and miR-210 in CTCs of breast cancer patients with verified metastasis and compared their expression levels in corresponding plasma and primary tumors. METHODS: Expression levels of the miRNAs were quantified by quantitative reverse transcription PCR (RT-qPCR) in (a) 89 primary breast tumors and 30 noncancerous breast tissues and (b) CTCs and corresponding plasma of 55 patients with metastatic breast cancer and 20 healthy donors. For 30 of these patients, CTCs, corresponding plasma, and primary tumor tissues were available. RESULTS: In formalin-fixed, paraffin-embedded tissues, these miRNAs were differentially expressed between primary breast tumors and noncancerous breast tissues. miR-21 (P < 0.001) and miR-146a (P = 0.001) were overexpressed, whereas miR-200c (P = 0.004) and miR-210 (P = 0.002) were underexpressed. In multivariate analysis, miR-146a overexpression was significantly [hazard ratio 2.969 (1.231 7.157), P = 0.015] associated with progression-free survival. In peripheral blood, all miRNAs studied were overexpressed in both CTC and corresponding plasma. There was a significant association between miR-21 expression levels in CTCs and plasma for 36 of 55 samples (P = 0.008). In plasma, ROC curve analysis revealed that miR-21, miR-146a, and miR-210 could discriminate patients from healthy individuals. CONCLUSIONS: Metastasis-related miRNAs are overexpressed in CTCs and corresponding plasma; miR-21 expression levels highly correlate in CTCs and plasma; and miR-21, miR-146a, and miR-210 are valuable plasma biomarkers for discriminating patients from healthy individuals. PMID- 27197675 TI - Iterative Outlier Removal: A Method for Identifying Outliers in Laboratory Recalibration Studies. AB - BACKGROUND: Extreme values that arise for any reason, including those through nonlaboratory measurement procedure-related processes (inadequate mixing, evaporation, mislabeling), lead to outliers and inflate errors in recalibration studies. We present an approach termed iterative outlier removal (IOR) for identifying such outliers. METHODS: We previously identified substantial laboratory drift in uric acid measurements in the Atherosclerosis Risk in Communities (ARIC) Study over time. Serum uric acid was originally measured in 1990-1992 on a Coulter DACOS instrument using an uricase-based measurement procedure. To recalibrate previous measured concentrations to a newer enzymatic colorimetric measurement procedure, uric acid was remeasured in 200 participants from stored plasma in 2011-2013 on a Beckman Olympus 480 autoanalyzer. To conduct IOR, we excluded data points >3 SDs from the mean difference. We continued this process using the resulting data until no outliers remained. RESULTS: IOR detected more outliers and yielded greater precision in simulation. The original mean difference (SD) in uric acid was 1.25 (0.62) mg/dL. After 4 iterations, 9 outliers were excluded, and the mean difference (SD) was 1.23 (0.45) mg/dL. Conducting only one round of outlier removal (standard approach) would have excluded 4 outliers [mean difference (SD) = 1.22 (0.51) mg/dL]. Applying the recalibration (derived from Deming regression) from each approach to the original measurements, the prevalence of hyperuricemia (>7 mg/dL) was 28.5% before IOR and 8.5% after IOR. CONCLUSIONS: IOR is a useful method for removal of extreme outliers irrelevant to recalibrating laboratory measurements, and identifies more extraneous outliers than the standard approach. PMID- 27197676 TI - Bloodborne Viral Pathogen Contamination in the Era of Laboratory Automation. AB - BACKGROUND: The CDC states that laboratory testing for persons under investigation for Ebola virus disease can be safely performed using automated laboratory instruments by adhering to bloodborne pathogen practices. We therefore sought to investigate the levels of viral contamination of a total laboratory automation (TLA) system to guide risk mitigation strategies for handling infectious agents. METHODS: Environmental swabs followed by PCR for hepatitis B (HBV) and hepatitis C (HCV) viruses were taken from a chemistry TLA system during routine clinical use and after running a small number of high-titer HCV samples. Control experiments were performed to ensure the recovery of DNA and RNA viruses by swabs from a representative nonporous surface. RESULTS: Of 79 baseline swabs for nucleic acids performed on the TLA system, 10 were positive for HBV and 8 for HCV. Viral nucleic acid was consistently detected from swabs taken from the distal inside surface of the decapper discharge chute, with areas adjacent to the decapper instrument and the centrifuge rotor also positive for HBV or HCV nucleic acid. Contamination was occasionally detected on exposed surfaces in areas without protective barriers between samples and personnel. After running known HCV-positive samples, at least one additional site of contamination was detected on an exposed area of the line. CONCLUSIONS: A low level of viral contamination of automated clinical laboratory equipment occurs in clinical use. Given the risks associated with highly infectious agents, there is a need for risk mitigation procedures when handling all samples. PMID- 27197677 TI - Selecting Statistical Procedures for Quality Control Planning Based on Risk Management. AB - BACKGROUND: According to the traditional approach to statistical QC planning, the performance of QC procedures is assessed in terms of its probability of rejecting an analytical run that contains critical size errors (PEDC). Recently, the maximum expected increase in the number of unacceptable patient results reported during the presence of an undetected out-of-control error condition [Max E(NUF)], has been proposed as an alternative QC performance measure because it is more related to the current introduction of risk management concepts for QC planning in the clinical laboratory. METHODS: We used a statistical model to investigate the relationship between PEDC and Max E(NUF) for simple QC procedures widely used in clinical laboratories and to construct charts relating Max E(NUF) with the capability of the analytical process that allow for QC planning based on the risk of harm to a patient due to the report of erroneous results. RESULTS: A QC procedure shows nearly the same Max E(NUF) value when used for controlling analytical processes with the same capability, and there is a close relationship between PEDC and Max E(NUF) for simple QC procedures; therefore, the value of PEDC can be estimated from the value of Max E(NUF) and vice versa. QC procedures selected by their high PEDC value are also characterized by a low value for Max E(NUF). CONCLUSIONS: The PEDC value can be used for estimating the probability of patient harm, allowing for the selection of appropriate QC procedures in QC planning based on risk management. PMID- 27197678 TI - Can't Touch This! Contamination of Laboratory Equipment with Bloodborne Pathogens. PMID- 27197679 TI - Advances in Lipid Testing: A Practical Step Forward. PMID- 27197680 TI - Demystifying Reference Sample Quality Control. PMID- 27197681 TI - Villonodular synovitis of the ankle. Analysis of the risk of recurrence. AB - INTRODUCTION: Villonodular synovitis (VNS) is a rare disease with an incidence of 1.8 per 1,000,000 inhabitants. VNS of the ankle has seldom been described and evaluated given its extreme rarity (2.5% of VNS cases). It presents an 11% recurrence rate. We report a continuous retrospective series with the main objective of clinically and radiologically evaluating these ankles searching for any risk factors of recurrence. At revision the study's main endpoint was the existence of local recurrence (radiological and clinical) and the secondary endpoint was the existence of tibiotalar osteoarthritis. The working hypothesis was that recurrence could be subclinical, warranting systematic imaging studies during follow-up. MATERIAL AND METHODS: The study was retrospective, conducted on seven patients (six males) whose mean age was 42 years treated over a period of 9 years (two diffuse forms and five localized forms). The initial treatment consisted in synovectomy via the conventional approach. Four patients also received adjuvant isotopic synoviorthesis treatment. The revision was clinical (MMTS, AOFAS, and OMAS scores) and radiological (standard and MRI) to evaluate the joint after-effects and search for recurrence. RESULTS: Six patients were seen at a mean 6.5 years of follow-up. One case of early recurrence (4 years) was noted, with a major clinical manifestation because it was associated with joint destruction requiring arthrodesis, and one case of late asymptomatic recurrence (9 years), diagnosed radiologically on the follow-up MRI. The functional results remained good at follow-up (MMTS 77%, AOFAS 71, OMAS 71). Five of the six patients returned to their daily activities. At revision, no sign of osteoarthritis was observed. No risk factor for recurrence was demonstrated. DISCUSSION/CONCLUSION: The hypothesis was confirmed with the existence of asymptomatic recurrence at revision, underscoring the value of systematic MRI at follow-up. Other than major joint destruction, the prognosis remains good even in case of recurrence. The literature emphasizes the existence of an initial diffuse form and partial surgical resection as risk factors of recurrence. None of the reports in the literature has proven that adjuvant treatment, whose modalities do not meet with consensus, reduces this risk. LEVEL OF EVIDENCE: Retrospective series, level IV. PMID- 27197682 TI - Serpentine supravenous hyperpigmentation due to hydroxychloroquine. PMID- 27197683 TI - Effects of smoking on central blood pressure and pressure amplification in hypertension of the young. AB - The aim of this study was to investigate the effect of cigarette smoking on peripheral and central blood pressure (BP) in a group of young stage I hypertensives. A total of 344 untreated subjects from the HARVEST study were examined (mean age 37+/-10 years). Patients were divided into three groups based on smoking status: non-smokers, light smokers (?5 cigarettes/day) and moderate-to heavy smokers (>5 cigarettes/day); and into three groups by age: 18-29, 30-39 and ?40 years. Central BP measurements and augmentation index (AIx) were calculated from brachial pressure waveform, with applanation tonometry, by means of the Specaway DAT System plus a Millar tonometer. The central waveform was derived from peripheral BP using the same software system of the SphygmoCor System pulse wave analysis. In addition, two indirect measurements of arterial stiffness were calculated: pulse pressure (PP) and systolic BP amplification. Central systolic BP and PP were higher in smokers than in non-smokers (systolic BP: 121.9+/-13.1 mmHg in non-smokers, 127.2+/-16.5 mmHg in light smokers, 126.7+/-15.3 mmHg in those who smoked >5 cigarettes/day, p=0.009; PP: 37.7+/-9.8 mmHg, 41.5+/-13.1 mmHg, 41.9+/-10.5 mmHg, respectively, p=0.005). Lower systolic BP amplification (p<0.001) and PP amplification (p=0.001) were observed in smokers compared to non smokers. In a two-way ANCOVA analysis, systolic BP amplification markedly declined across the three age groups (p=0.0002) and from non-smokers to smokers (p=0.0001), with a significant interaction between smoking and age group (p=0.05). The AIx was higher in smokers compared to non-smokers (p=0.024). In young hypertensives, smoking has a detrimental effect on central BP, accelerating the age-related decline in BP amplification. PMID- 27197685 TI - Urban climate versus global climate change-what makes the difference for dengue? AB - The expansion in the geographical distribution of vector-borne diseases is a much emphasized consequence of climate change, as are the consequences of urbanization for diseases that are already endemic, which may be even more important for public health. In this paper, we focus on dengue, the most widespread urban vector-borne disease. Largely urban with a tropical/subtropical distribution and vectored by a domesticated mosquito, Aedes aegypti, dengue poses a serious public health threat. Temperature plays a determinant role in dengue epidemic potential, affecting crucial parts of the mosquito and viral life cycles. The urban predilection of the mosquito species will further exacerbate the impact of global temperature change because of the urban heat island effect. Even within a city, temperatures can vary by 10 degrees C according to urban land use, and diurnal temperature range (DTR) can be even greater. DTR has been shown to contribute significantly to dengue epidemic potential. Unraveling the importance of within city temperature is as important for dengue as for the negative health consequences of high temperatures that have thus far been emphasized, for example, pollution and heat stroke. Urban and landscape planning designed to mitigate the non-infectious negative effects of temperature should additionally focus on dengue, which is currently spreading worldwide with no signs of respite. PMID- 27197684 TI - Study on the efficacy of surgery of the superficial venous system and of compression therapy at early stages of chronic venous disease for the prevention of chronic venous ulceration. AB - The mainstay of treatment of chronic venous ulceration (CVU), as also suggested by current treatment guidelines for chronic venous disease (CVD), is represented by surgery and compression therapy for which there is strong evidence of their role in clinically relevant improvement in wound healing and also in the reduction of CVU recurrence, but no information is available as to whether or not these treatments provide effective protection from the onset of CVU. In our study, we have followed, for a median time of 13 years, a total of 3947 patients with CVD at classes C2-C3 of CEAP classification, treated with our treatment protocol (surgery and compression therapy) in order to track the natural history of these patients with regards to CVU development. We identified four groups of patients: 2354 patients (59.64%) (Group A) fully adherent to protocols; 848 patients (21.48%) (Group B) fully adherent to surgery and non-compliant to compression therapy; 432 patients (10.95%) (Group C) fully adherent to compression therapy and non-compliant to surgery; and 313 patients (7.93%) (Group D) non-compliant to either treatments. Regardless of compliance to treatments, the ulcer development rates were very similar between groups (range: 3.23-4.79%), with no statistical significance (P = 0.1522). Currents treatments used in the early stages of CVD appear to have no effects to progression to CVU. Additional longitudinal studies are required to confirm these findings. PMID- 27197687 TI - Metformin-Associated Lactic Acidosis in a Patient with Normal Renal Function. AB - We report a case of metformin-associated lactic acidosis (MALA) in the setting of normal renal function and review the relevant medical literature. A 77-year-old female diagnosed with type 2 diabetes mellitus previously treated with insulin and gliclazide MR was started on metformin. A few weeks later, she was found to have lactic acidosis. Renal function was normal, and no severe underlying illness was identified. Metformin was discontinued, and lactate levels normalized within 4 days, suggesting metformin was a reversible precipitant of the lactic acidosis. MALA can occur in the absence of renal impairment, systemic hypoperfusion or severe liver disease. A possible mechanism is a genetically determined alteration in metformin pharmacokinetics. Metformin is beneficial and safe in patients with normal renal function, but the development of MALA, although rare, should be kept in mind to prevent potentially life-threatening toxicity. PMID- 27197686 TI - Performance of the Pediatric Glasgow Coma Scale Score in the Evaluation of Children With Blunt Head Trauma. AB - OBJECTIVE: The objective was to compare the accuracy of the pediatric Glasgow Coma Scale (GCS) score in preverbal children to the standard GCS score in older children for identifying those with traumatic brain injuries (TBIs) after blunt head trauma. METHODS: This was a planned secondary analysis of a large prospective observational multicenter cohort study of children with blunt head trauma. Clinical data were recorded onto case report forms before computed tomography (CT) results or clinical outcomes were known. The total and component GCS scores were assigned by the physician at initial emergency department evaluation. The pediatric GCS was used for children <2 years old and the standard GCS for those >=2 years old. Outcomes were TBI visible on CT and clinically important TBI (ciTBI), defined as death from TBI, neurosurgery, intubation for more than 24 hours for the head injury, or hospitalization for 2 or more nights for the head injury in association with TBI on CT. We compared the areas under the receiver operating characteristic (ROC) curves between age cohorts for the association of GCS and the TBI outcomes. RESULTS: We enrolled 42,041 patients, of whom 10,499 (25.0%) were <2 years old. Among patients <2 years, 313/3,329 (9.4%, 95% confidence interval [CI] = 8.4% to 10.4%) of those imaged had TBIs on CT and 146/10,499 (1.4%, 95% CI = 1.2% to 1.6%) had ciTBIs. In patients >=2 years, 773/11,977 (6.5%, 95% CI = 6.0% to 6.9%) of those imaged had TBIs on CT and 572/31,542 (1.8%, 95% CI = 1.7% to 2.0%) had ciTBIs. For the pediatric GCS in children <2 years old, the area under the ROC curve was 0.61 (95% CI = 0.59 to 0.64) for TBI on CT and 0.77 (95% CI = 0.73 to 0.81) for ciTBI. For the standard GCS in older children, the area under the ROC curve was 0.71 (95% CI = 0.70 to 0.73) for TBI on CT scan and 0.81 (95% CI = 0.79 to 0.83) for ciTBI. CONCLUSIONS: The pediatric GCS for preverbal children was somewhat less accurate than the standard GCS for older children in identifying those with TBI on CT. However, the pediatric GCS for preverbal children and the standard GCS for older children were equally accurate for identifying ciTBI. PMID- 27197689 TI - Alloimmunisation rates of sickle cell disease patients in the United States differ from those in other geographical regions. AB - OBJECTIVES: Comparison of the alloimmunisation rates of patients with sickle cell disease in the Unites States versus other countries. BACKGROUND: Sickle cell disease (SCD) patients treated with chronic transfusion therapy are at a high risk of red blood cell (RBC) alloimmunisation. MATERIALS AND METHODS: We reviewed published literature describing alloimmunisation rates of SCD patients. Average alloimmunisation rates and number of alloantibodies per transfused patient in the United States and other countries were evaluated. RESULTS: Twenty-four studies on alloimmunisation of SCD patients were found, 15 studies with 3,708 patients in the US and 9 studies with 2203 patients from other regions, including South America, the Caribbean, Middle East, Africa and Europe. The United States has a higher alloimmunisation rate (22.33 +/- 0.13% versus 16.25 +/- 0.35%, p < 0.0001) and a higher number of alloantibodies per transfused patient (0.45 +/- 0.003 versus 0.20 +/- 0.005, p < 0.0001) than other countries. Brazil with a higher proportion of multi-ethnic donors demonstrated a lower alloimmunisation rate compared to the United States (14.60 +/- 0.40% versus 22.33 +/- 0.13%, p < 0.0001) and fewer alloantibodies per transfused patient (0.20 +/- 0.02 versus 0.45 +/- 0.003, p < 0.0001) than the United States. CONCLUSION: SCD patients in the United States had a higher alloimmunisation rate, which could be reduced by a more ethnically diverse donor pool and a more conservative transfusion strategy in non-critical conditions. PMID- 27197688 TI - Polyol accumulation in muscle and liver in a mouse model of type 2 diabetes. AB - AIMS: Type 2 diabetes (T2D) is a complex metabolic disease leading to complications in multiple organs. Diabetic myopathy and liver disease are common complications of T2D, but are incompletely understood. To gain insight into the pathogenesis of these conditions we performed metabolomic analysis of skeletal muscle and liver in a mouse model of T2D. METHODS: Tissue metabolomics were performed by GC/MS and LC/MS of the skeletal muscle and liver in the MKR mouse model of T2D, compared with control mice. MKR mice were treated with the beta-3 adrenergic receptor agonist, CL-316,243 to determine metabolite changes after correcting hyperglycemia. RESULTS: Blood glucose was higher in MKR vs WT mice, and normalized with CL-316,243 treatment. Compared with WT mice, MKR mice had 2.5 fold higher concentrations of sorbitol and 1.7 fold lower concentrations of reduced glutathione in skeletal muscle. In liver, MKR mice had 2 fold higher concentrations of the pentitol ribitol. CL-316,243 treatment normalized sorbitol and ribitol concentrations in MKR skeletal muscle and liver, respectively to the levels of the WT mice. CONCLUSIONS: These results demonstrate tissue-specific accumulation of polyols in a mouse model of T2D and provide novel insights into the pathogenesis of myopathy and liver disease in T2D. PMID- 27197691 TI - Drivers of costly treatment strategies in rheumatoid arthritis. PMID- 27197692 TI - Microbiome Data Science: Understanding Our Microbial Planet. AB - Microbiology is experiencing a revolution brought on by recent developments in sequencing technology. The unprecedented volume of microbiome data being generated poses significant challenges that are currently hindering progress in the field. Here, we outline the major bottlenecks and propose a vision to advance microbiome research as a data-driven science. PMID- 27197690 TI - Tumour necrosis factor inhibition versus rituximab for patients with rheumatoid arthritis who require biological treatment (ORBIT): an open-label, randomised controlled, non-inferiority, trial. AB - BACKGROUND: Tumour necrosis factor (TNF) inhibition and B-cell depletion are highly effective treatments for active rheumatoid arthritis, but so far no randomised controlled trials have directly compared their safety, efficacy, and cost-effectiveness. This study was done to test the hypothesis that using rituximab would be clinically non-inferior and cheaper compared with TNF inhibitor treatment in biological-treatment naive patients with rheumatoid arthritis. METHODS: This open-label, randomised controlled, non-inferiority trial enrolled patients with active, seropositive rheumatoid arthritis and an inadequate response to synthetic disease modifying anti-rheumatic drugs (DMARDs) from 35 rheumatology departments in the UK. Patients were randomly assigned 1:1 to the rituximab or TNF inhibitor groups with minimisation to account for methotrexate intolerance using a web-based randomisation system. Patients were given intravenous rituximab 1 g on days 1 and 15, and after 26 weeks if they responded to treatment but had persistent disease activity (28 joint count disease activity score [DAS28-ESR] >3.2; rituximab group) or a TNF inhibitor adalimumab (40 mg subcutaneously every other week) or etanercept (50 mg per week subcutaneously) according to the patient's and rheumatologist's choice (TNF inhibitor group). Patients could switch treatment in the case of drug-related toxic effects or absence or loss of response. The primary outcome measure was the change in DAS28-ESR between 0 and 12 months in the per-protocol population of patients who were assigned to treatment and remained in follow-up to 1 year. We assessed safety in all patients who received at least one dose of study drug. We also assessed the cost-effectiveness of each strategy. The non-inferiority margin was specified as 0.6 DAS28-ESR units. This study is registered with ClinicalTrials.gov, number NCT01021735. FINDINGS: Between April 6, 2009, and Nov 11, 2013, 295 patients were randomly assigned and given either rituximab (n=144) or TNF inhibitor (n=151) treatment. After 12 months, the change in DAS28-ESR for patients assigned to rituximab was -2.6 (SD 1.4) and TNF inhibitor was -2.4 (SD 1.5), with a difference within the prespecified non-inferiority margin of -0.19 (95% CI -0.51 to 0.13; p=0.24). The health-related costs associated with the rituximab strategy were lower than the TNF inhibitor strategy (L9,405 vs L11,523 per patient, p<0.0001). 137 (95%) of 144 patients in the rituximab group and 143 (95%) of 151 patients in the TNF inhibitor group had adverse events. 37 serious adverse events occurred in patients receiving rituximab compared with 26 in patients receiving TNF inhibitors, of which 27 were deemed to be possibly, probably, or definitely related to the treatment (15 vs 12, p=0.5462). One patient in each group died during the study. INTERPRETATION: Initial treatment with rituximab is non-inferior to initial TNF inhibitor treatment in patients seropositive for rheumatoid arthritis and naive to treatment with biologicals, and is cost saving over 12 months. FUNDING: Arthritis Research UK, Roche. PMID- 27197693 TI - Binding activities of non-beta-glucan glycoclusters to dectin-1 and exploration of their binding site. AB - Dectin-1, which specifically recognizes beta-(1,3)-glucans, plays an important role in innate immune responses. For the first time, in this study we found that a series of non-beta-glucan glycoclusters can bind to dectin-1 by means of surface plasmon resonance (SPR) assay. Hexavalent lactoside Ju-6 showed the strongest affinity property (KD=1.6 uM). Interestingly, a continuous binding dissociation experiment on SPR showed that Ju-6 and Laminarin binding to dectin-1 are independent of each other. Moreover, RT-PCR assay showed that Ju-6 cannot up regulate cytokine gene expression or inhibit the promoting effect caused by Zymosan (a long-chain beta-glucan). These results indicated that there might be a possible new carbohydrate binding site on dectin-1. PMID- 27197695 TI - [Erratum of "In time: averting the legacy of kidney disease - focus on childhood" [Rev Paul Pediatr. 2016;34(1):5-10]]. PMID- 27197694 TI - Evaluation of a two-stage antibacterial hydrogel dressing for healing in an infected diabetic wound. AB - Various types of wound dressings have been used to treat complex infections in diabetes mellitus. This study is the first to evaluate the healing effects using a two-stage dressing in infected diabetic wounds. A two-stage antibacterial hydrogel dressing (two-stage dressing) was established with two time phases, an antibacterial phase and a drug release phase. We established each phase by using a swelling and rate of drug release test. These results suggested that the antimicrobial phase is activated as soon as the two-stage dressing attaches to the skin. The drugs in the drug release layer of the dressing were released to a greater extent than expected 20-36 h after attachment to the skin, likely due to extensive water absorption. Histological analysis and measurement of vascular endothelial growth factor expression through in vivo testing suggested that the benefits of a two-stage dressing include rapid antibacterial properties, sustained drug release, and promotion of wound healing through cell proliferation as compared with the traditional composite antibacterial hydrogel dressing. Further in vivo tests confirmed that separation of the antibacterial and drug releasing properties, along with biocompatibility and rapid wound closure rates made two-stage dressings suitable for healing of infected wounds. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1808-1817, 2017. PMID- 27197696 TI - Understanding parents' and professionals' knowledge and awareness of autism in Nepal. AB - Autism is a global phenomenon. Yet, there is a dearth of knowledge of how it is understood and its impact in low-income countries. We examined parents' and professionals' understanding of autism in one low-income country, Nepal. We conducted focus groups and semi-structured interviews with parents of autistic and non-autistic children and education and health professionals from urban and rural settings ( n = 106), asking questions about typical and atypical development and presenting vignettes of children to prompt discussion. Overall, parents of typically developing children and professionals had little explicit awareness of autism. They did, however, use some distinctive terms to describe children with autism from children with other developmental conditions. Furthermore, most participants felt that environmental factors, including in utero stressors and birth complications, parenting style and home or school environment were key causes of atypical child development and further called for greater efforts to raise awareness and build community capacity to address autism. This is the first study to show the striking lack of awareness of autism by parents and professionals alike. These results have important implications for future work in Nepal aiming both to estimate the prevalence of autism and to enhance support available for autistic children and their families. PMID- 27197697 TI - Personality traits, autobiographical memory and knowledge of self and others: A comparative study in young people with autism spectrum disorder. AB - The relationship between dissociable components of autobiographical memory (e.g. semantic personality traits and episodic memory retrieval) and other cognitive skills that are proposed to enable one to develop a sense of self (e.g. introspection) have not previously been explored for children with autism spectrum disorder. This study compared autobiographical memory (semantic and episodic) and knowledge of self (internal/external self-knowledge and introspection/mentalising abilities) in children (aged 11-18 years) with high functioning autism spectrum disorder and typically developing controls (total N = 48). Novel and standard tasks were employed. Compared to typically developing controls, young people with autism spectrum disorder had autobiographical memory difficulties that were characterised by a reduction in the retrieval of semantic personality traits, with more initial prompts required to facilitate episodic memory retrieval and fewer episodic memories containing emotional and sensory information. Knowledge of the self and others was also impaired, with reduced introspection and poorer mentalising abilities. Young people with autism spectrum disorder were also identified as presenting with an atypical relationship between autobiographical memory and self-knowledge, which was significantly different from typically developing controls. Test performance is discussed in relation to the functions of autobiographical memory, with consideration of how these cognitive difficulties may contribute to clinical practices and the social and behavioural characteristics of autism spectrum disorder. PMID- 27197698 TI - Reply to Umberto Capitanio, Paolo Dell'Oglio, Alessandro Larcher, and Francesco Montorsi's Reply to Kazutaka Saito's Words of Wisdom re: Nephron-sparing Techniques Independently Decrease the Risk of Cardiovascular Events Relative to Radical Nephrectomy in Patients with a T1a-T1b Renal Mass and Normal Preoperative Renal Function. Eur Urol. 2016;69:538. PMID- 27197699 TI - Impaired Mood in Headache Clinic Patients: Associations With the Perceived Hindrance and Attainability of Personal Goals. AB - BACKGROUND: Headache disorders are often accompanied by impaired mood, especially in the headache clinic population. There is a large body of literature demonstrating that an illness or disability may affect the way in which patients perceive their personal goals and that the perception that the attainability of goals is hindered by the illness is a risk factor for impaired mood. However, empirical evidence regarding the extent to which goals are hindered or less attainable as a result of a headache disorder, and how that is related to mood, is currently lacking. OBJECTIVE: The aim of this cross-sectional study was to examine associations between headache severity, goal hindrance and attainability, and mood in a headache clinic population. METHODS: The sample consisted of 65 adult patients seeking treatment at a tertiary headache clinic. Prior to their first appointment in the clinic, patients completed self-report measures of headache severity, goals and mood (PANAS). RESULTS: Higher self-reported headache intensity was associated with higher goal hindrance (r = .38, P = .004), whereas greater headache frequency was associated with lower goal attainability (r = .30, P = .022). Higher perceived goal hindrance was associated with lower positive mood (r = -.27, P = .032) and higher negative mood (r = .28, P = .027). Furthermore, lower perceived goal attainability was associated with higher negative mood (r = -.34, P = .007). Goal perceptions explained an additional 11.4% of the variance in positive mood (F = 3.250, P = .047 <.05) and 10.5% of the variance in negative mood (F = 3.459, P = .039) beyond the effect of age and headache severity. CONCLUSION: The results of this preliminary study suggest that perceptions of increased goal hindrance and decreased goal attainability may indeed be a risk factor for impaired mood in the headache clinic population and highlight the need for further, longitudinal research. Obtaining more insight into goal processes (eg, what types of goals are specifically disturbed, which goal adjustment strategies are (mal)adaptive) may help to identify ways to improve outcomes in the headache clinic population. PMID- 27197700 TI - The effect of social capital on job satisfaction and quality of care among hospital nurses in South Korea. AB - AIM: To identify the level of social capital and its effect on job satisfaction and self-reported quality of care of nurses working in hospital settings in South Korea. BACKGROUND: There are few studies on social capital and its relationship to workplace outcomes in the nursing profession internationally. METHOD: A cross sectional, correlational design was adopted with a convenience sample of 432 nurses from two university-affiliated teaching hospitals in South Korea. RESULTS: Nurses' social capital was positively related to job satisfaction and self reported quality of care. Social capital explained 50% and 24%, respectively, of the variance in job satisfaction and reported quality of care. CONCLUSION: By improving social capital, nurses' job satisfaction could be enhanced and result in better quality of care for patients. IMPLICATIONS FOR NURSING MANAGEMENT: Strategies to improve social capital in nursing organisations are necessary to improve job satisfaction and the quality of care provided by nurses. Nurse managers and administrators should encourage nurse participation in organisational affairs and decision-making processes to improve social capital by developing a trusting work environment with shared values and support nurses who work with peers, superiors, and subordinates. PMID- 27197701 TI - Transcutaneous temperature controlled radiofrequency for orgasmic dysfunction. AB - BACKGROUND AND OBJECTIVES: To evaluate the safety, tolerability, and clinical efficacy of transcutaneous temperature controlled radiofrequency (TTCRF) on vulvovaginal tissue for orgasmic dysfunction. STUDY DESIGN/MATERIALS AND METHODS: Subjects included 25 sexually active women, ages 21-65, with self-reported difficulty in achieving orgasms during sex (anorgasmic or slow-to-orgasm). Each patient received three sessions at intervals of about 1 month. Treatment was performed using a slim S-shaped probe with a stamp-sized metal radiofrequency emitter on one surface of the tip (25 minutes total time on average). External treatments covered the labia majora and minora, lower mons pubis, perineal body, clitoral hood, and clitoris. Full length treatment of the vagina with concentration on the anterior wall was performed. Tissue temperature during therapy was elevated to and maintained between 40 degrees C and 45 degrees C. No anesthesia was required. After treatment, patients immediately resumed normal activities, including sex. RESULTS: Twenty-three of 25 patients reported an average reduction in time to orgasm of 33%. Patients also noted significant vaginal tightening effects, increased vaginal moisture, and improved vulvar and clitoral sensitivity. All anorgasmic patients reported the ability to achieve orgasms. Two patients had minimal response. CONCLUSION: TTCRF is an effective non hormonal, non-surgical option for women having difficulty achieving orgasm. Treatment also has visible tightening effects on feminine tissues and appears to increase local blood flow, resulting in increased vaginal tightness and moisture. Improved appearance and friction resulted in improved confidence and reduced performance anxiety. Lasers Surg. Med. 48:641-645, 2016. (c) 2016 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc. PMID- 27197703 TI - Technical Standards for Nursing Education Programs in the 21st Century. AB - PURPOSE: The Institute of Medicine (2000, 2002) exposed serious safety problems in the health system and called for total qualitative system change. The Institute of Medicine (2011, 2015) also calls for improving the education of nurses to provide leadership for a redesigned health system. Intertwined with improving education is the need to recruit and retain diverse highly qualified students. Disability is part of diversity inclusion, but current technical standards (nonacademic requirements) for admission to many nursing programs are a barrier to the entry of persons with disabilities. Rehabilitation nurse leaders are in a unique position to improve disability diversity in nursing. The purpose of this paper is to discuss the importance of disability diversity in nursing. DESIGN: The history of existing technical standards used in many nursing programs is reviewed along with examples. METHODS: On the basis of the concept that disability inclusion is a part of diversity inclusion, we propose a new model of technical standards for nursing education. CONCLUSION AND CLINICAL RELEVANCE: Rehabilitation nurse leaders can lead in eliminating barriers to persons with disabilities entering nursing. PMID- 27197702 TI - Developing a Web-Based Version of An Exercise-Based Rehabilitation Program for People With Chronic Knee and Hip Pain: A Mixed Methods Study. AB - BACKGROUND: Osteoarthritis is highly prevalent and has enormous personal and socioeconomic impact. Enabling Self-management and Coping with Arthritic Pain through Exercise (ESCAPE-pain) is an integrated rehabilitation program that helps people understand how exercise can improve physical and psychosocial well-being. Unfortunately, its availability is limited. A Web-based version of the program could increase access for more people. Many Web-based resources are developed without end-user input and result in over-complex, unwanted, ineffective products with limited uptake. OBJECTIVE: The objective of this study was to codesign a Web based version of ESCAPE-pain that people with chronic joint pain find engaging, informative, and useful. METHODS: To establish older persons' Internet use we conducted a postal survey of 200 people. To establish their opinions, likes or dislikes, and requirements for a Web-based version of the ESCAPE-pain program, we conducted two focus groups with 11 people who had participated in a program based on ESCAPE-pain and two with 13 people who had not. Information from the postal survey and focus groups was used to develop an online prototype website. People's opinions of the prototype website were gauged from thematic analysis of eight semistructured "think aloud" interviews. RESULTS: The survey response rate was 42% (83/200), of whom 67% (56/83) were female and mean age was 67 years. Eighty three percent of the people had used the Internet, 69% described themselves as either very confident or confident Internet users, and 77% had looked online for health information. With regard to participating online, 34% had read a commentary or watched a video of someone else's experience of a health problem and 23% had tracked a health issue. Key qualitative themes emerged that included engagement, acceptability and usability, and structure and content of the program. CONCLUSIONS: Older people use the Internet as a source of health information but have concerns about safe use and quality of information. Users require a credible website that provides personalized information, support, monitoring, and feedback. PMID- 27197705 TI - Do dental students have a neutral working posture? AB - BACKGROUND: Dentists are susceptible to Musculoskeletal Disorders (MSDs) due to prolonged static postures. To prevent MSDs, working postures of dental students should be assessed and corrected in early career life. OBJECTIVE: This study estimated the risk of developing musculoskeletal disorders in dental students using Rapid Upper Limb Assessment (RULA) tool. METHODS: A number of 103 undergraduate dental students from fourth and fifth academic years participated. Postures of these students were assessed using RULA tool while working in the dental clinic. They also answered a questionnaire regarding their knowledge about postural dental ergonomic principles. RESULTS: The majority of the students (66%) were at intermediate and high risk levels to develop MSDs and their postures needed to be corrected. There was no significant correlation between RULA score and gender, academic year and different wards of dental clinics. There was no significant correlation between knowledge and RULA scores. CONCLUSIONS: Dental students did not have favorable working postures. They were at an intermediate to high risk for developing MSDs which calls for a change in their working postures. Therefore students should be trained with ergonomic principles and to achieve the best results, ergonomic lessons should be accompanied by practice and periodical evaluations. PMID- 27197704 TI - Effects of carbohydrate/protein ratio on the microstructure and the barrier and sorption properties of wheat starch-whey protein blend edible films. AB - BACKGROUND: Starch and whey protein isolate and their mixtures were used for making edible films. Moisture sorption isotherms, water vapour permeability, sorption of aroma compounds, microstructure, water contact angle and surface properties were investigated. RESULTS: With increasing protein content, the microstructure changes became more homogeneous. The water vapour permeability increases with both the humidity gradient and the starch content. For all films, the hygroscopicity increases with starch content. Surface properties change according to the starch/whey protein ratio and are mainly related to the polar component of the surface tension. Films composed of 80% starch and 20% whey proteins have more hydrophobic surfaces than the other films due to specific interactions. CONCLUSIONS: The effect of carbohydrate/protein ratio significantly influences the microstructure, the surface wettability and the barrier properties of wheat starch-whey protein blend films. (c) 2016 Society of Chemical Industry. PMID- 27197706 TI - Effects of hamstring stretch with pelvic control on pain and work ability in standing workers. AB - BACKGROUND: Hamstring tightness induces posterior pelvic tilt and decreased lumbar lordosis, which can result in low back painOBJECTIVE: We investigated effects of hamstring stretch with pelvic control on pain and work ability in standing workers. METHODS: One hundred adult volunteers from a standing workers were randomly assigned to pelvic control hamstring stretching (PCHS) (n = 34), general hamstring stretching (GHS) (n = 34), control (n = 32) groups. The control group was performed self-home exercise. All interventions were conducted 3 days per week for 6 weeks, and included in the hamstring stretching and lumbopelvic muscle strengthening. Outcomes were evaluated through the visual analog scale (VAS), straight leg raise test (SLR), sit and reach test (SRT), Oswestry disability index (ODI), and work ability index (WAI). RESULTS: Significant difference in VAS, SLR, SRT, ODI, and WAI were found in the PCHS and GHS groups. The control group was a significant difference only in ODI. The PCHS group showed a greater difference than the GHS group and control group in VAS, SLR, SRT, and ODI. CONCLUSIONS: The pelvic control hamstring stretch exercise would be more helpful in back pain reduction and improvement of work ability in an industrial setting. PMID- 27197707 TI - Differences in the activation of abdominal muscles during trunk extension between smokers and non-smokers. AB - BACKGROUND: Many studies reported that the morbidity of the respiratory and circulatory diseases is higher among smokers than non-smokers. Some recent studies reported the effects of smoking on the musculoskeletal system. However, it is difficult to generalize the experimental environment because it is different from activities of daily living environment. OBJECTIVE: The purpose of this study was to compare the differences in the activation of abdominal muscles during trunk extension between smokers and non-smokers. METHODS: The subjects were 30 healthy adults (15 smokers and 15 non-smokers). The percentage of maximal voluntary isometric contraction (%MVIC) values of rectus abdominis (RA), external oblique (EO), internal oblique and transversus abdominis(IO&TrA) were measured using the surface electromyography System. RESULTS: The results showed no significant differences in the %MVIC of RA and EO between smokers and non smokers. However, the %MVIC of IO&TrA showed a significant difference between smokers and non-smokers. The %MVIC of IO&TrA of non-smokers was higher. CONCLUSIONS: The non-smokers showed greater activation of deep abdominal muscles than smokers did. PMID- 27197708 TI - Suprascapular nerve injury: A cause to consider in shoulder pain and dysfunction. AB - Suprascapular nerve injury is increasingly being recognized as an important cause of shoulder dysfunction. The non-specific clinical features of suprascapular nerve injury can make diagnosis difficult. However, it is essential for clinicians to consider it as part of the differential diagnoses in patients with vague pain or sensory disturbances over the posterosuperior part of their shoulder or have unexplained atrophy and weakness of their supraspinatus or infraspinatus muscle. Electrodiagnostic studies are useful in confirming and localising the nerve injury, while MRIs can be employed to determine the cause of nerve injury and assess the integrity of the rotator cuff muscles. Isolated suprascapular nerve injury can be managed with a trial of conservative management for at least 6 months. Subsequently, decompression of the nerve through open or arthroscopic techniques can be considered - both are associated with high rates of pain relief and functional improvement. PMID- 27197709 TI - Posttraumatic Growth in Relation to the Frequency and Severity of Traumatic Experiences Among Police Officers in Small to Midsize Departments. AB - The Critical Incident History Questionnaire (CIHQ) measures, through multiple measurement methods, the severity and frequency of traumatic events experienced by law enforcement officers. We, however, found no studies utilizing the CIHQ to examine posttraumatic growth (PTG) as measured by the Posttraumatic Growth Inventory. The purpose of this brief report was to assess the strength and direction of the relationships between PTG with trauma frequency, trauma severity, and health variables, including subjective traumatic stress, relationship stress, nontraumatic work stress, posttraumatic stress disorder (PTSD) symptoms, depression, and alcohol use among law enforcement officers (N = 193) from small and midsize agencies. In addition, we sought to explore differences between cognitive and behavioral PTG. Based on results from bivariate and multivariate analyses, we found that an idiosyncratic view of trauma severity shaped by personal experience demonstrated the strongest relationship with PTG among the frequency and severity variables and that increased PTG was not associated with reduced psychological distress. Alcohol use, a variable that is assessed primarily through behaviors compared with cognitions, was not significantly associated with PTG. Overall, the findings of this study demonstrate the importance for future research to consider both the frequency and severity of trauma exposure in the development of PTG and its impact on health outcomes. PMID- 27197710 TI - Lying to ourselves: rationality, critical reflexivity, and the moral order as 'structured agency'. AB - A report suggests that United States' army officers may engage in dishonest reporting regarding their compliance procedures. Similarly, nurses with espoused high ethical standards sometimes fail to live up to them and may do so while deceiving themselves about such practices. Reasons for lapses are complex. However, multitudinous managerial demands arising within 'technical and instrumental rationality' may impact on honest decision-making. This paper suggests that compliance processes, which operates within the social structural context of the technical and instrumental rationality manifest as 'managerialism', contributes to professional 'dishonesty' about lapses in care, sometimes through 'thoughtlessness'. The need to manage risk, measure, account, and control in order to deliver efficiency, effectiveness, and economy (technical rationality) thus has both unintended and dysfunctional consequences. Meeting compliance requirements may be mediated by factors such as the 'affect heuristic' and 'reflexive deliberations' as part of the 'structured agency' of nurses. It is the complexity of 'structured agency' which may explain why some nurses fail to respond to such things as sentinel events, a failure to recognize 'personal troubles' as 'public issues', a failure which to outsiders who expect rational and professional responses may seem inconceivable. There is a need to understand these processes so that nurses can critique the context in which they work and to move beyond either/or explanations of structure or agency for care failures, and professional dishonesty. PMID- 27197711 TI - Cost-effectiveness analysis of hepatocellular carcinoma screening by combinations of ultrasound and alpha-fetoprotein among Alaska Native people, 1983-2012. AB - BACKGROUND: The American Association for the Study of Liver Diseases (AASLD) recommends semi-annual hepatocellular carcinoma (HCC) screening using ultrasound (US) in persons with chronic hepatitis B (CHB) virus infection at high risk for HCC such as Asian males aged >=40 years and Asian females aged >=50 years. OBJECTIVE: To analyse the cost-effectiveness of 2 HCC screening methods in the Alaska Native (AN) health system: US-alone, or screening by alpha-fetoprotein (AFP) initially and switching to US for subsequent screenings if AFP >10 ng/mL (AFP->US). DESIGN: A spreadsheet-based model was developed for accounting the costs of 2 hypothetical HCC screening methods. We used epidemiologic data from a cohort of 839 AN persons with CHB who were offered HCC screening by AFP/US semi annually during 1983-2012. We assumed that compared with AFP->US, US-alone identifies 33% more tumours at an early stage (defined as a single tumour <=5 cm or <=3 tumours <=3 cm in diameter). Years of life gained (YLG) attributed to screening was estimated by comparing additional years of survival among persons with early- compared with late-stage tumours. Screening costs were calculated using Medicare reimbursement rates in 2012. Future screening costs and YLG were projected over a 30-year time horizon using a 3% discount rate. RESULTS: The total cost of screening for the cohort by AFP->US would have been approximately $357,000 ($36,000/early-stage tumour detected) compared to $814,000 ($59,000/early-stage tumour detected) by US-alone. The AFP->US method would have yielded an additional 27.8 YLG ($13,000/YLG) compared with 38.9 YLG ($21,000/YLG) for US-alone. Screening by US-alone would incur an additional $114,000 per extra early-tumour detected compared with AFP->US and $41,000 per extra YLG. CONCLUSIONS: Although US-alone HCC screening might have yielded more YLG than AFP >US, the reduced costs of the AFP->US method could expand access to HCC screening in resource constrained settings. PMID- 27197712 TI - Sarcomatoid carcinoma of the prostate with adenocarcinoma, squamous cell carcinoma, and heterologous components. PMID- 27197713 TI - Risk analysis of ischemic-type biliary lesions after liver transplant using octogenarian donors. PMID- 27197714 TI - The impact of geographical location on trends in hospitalisation rates and outcomes for fall-related injuries in older people. AB - OBJECTIVE: This population-based study investigates the influence of geographical location on hospital admissions, utilisation and outcomes for fall-related injury in older adults, adjusting for age, sex and comorbidities. METHODS: A linked dataset of all admissions of NSW residents aged 65 and older, hospitalised at least once for a fall-related injury between 2003 and 2012, was used to estimate rates of hospitalisations, total lengths-of-stay, 28-day readmissions, and 30-day mortalities. These were standardised for age, sex, comorbidity, and remoteness. RESULTS: Compared to urban residents, rural residents were hospitalised less (p<0.0001) and hospitalisation rates increased at a lower rate (0.8% vs 2.6% per year) from 2003 to 2012. Rural residents had a shorter median total length of stay (5 vs 7 days, p<0.0001), a higher 28-day readmission rate (18.9% vs 17.0%, p<0.0001) and higher 30-day mortality (5.0% vs 4.9%, p=0.0046). CONCLUSIONS: Over the study period, rural residents of NSW had lower rates of fall-related injury hospitalisation and a lower annual increase in hospitalisation rates compared to urban residents. When hospitalised, rural residents had a shorter length-of-stay, but higher rates of readmission and mortality. These differences existed following standardisation. IMPLICATIONS: This study highlights the need for further research to characterise and explain this variability. PMID- 27197716 TI - Chronic hepatitis C burden and care cascade in Australia in the era of interferon based treatment. AB - BACKGROUND AND AIM: Interferon-free direct-acting antiviral regimens for hepatitis C virus (HCV) infection have been recently available in Australia, beginning a new era in clinical and public health management of HCV infection. This study provided updated estimates of the HCV infection care cascade and burden in Australia as a reliable platform for assessing the future impact of interferon-free therapies. METHODS: A modeling approach was applied to estimate the number of individuals living with chronic HCV infection and with various liver disease stages. Data from national registries of HCV notification and liver transplantation, literature review, and expert consensus informed the model parameters. HCV notification and Pharmaceutical Benefits Scheme data were used to estimate the number of HCV diagnosed individuals and treatment uptake. RESULTS: In 2014, an estimated 230 470 individuals (range: 180 490-243 990) were living with HCV, among whom 75% were diagnosed (n = 172 720; range: 156 720-188 770), 20% had ever received treatment (n = 45 000; range: 39 280-50 720), and 11% had been cured (n = 24 750; range: 21 520-27 990). Among individuals with HCV infection, the proportion with hepatic fibrosis stage >=F3 doubled during the last decade, increasing from 9% (n = 18 580) in 2004 to 19% (n = 44,730) in 2014. Individuals initiating HCV treatment increased from 1100 in 1997 to 3840 in 2007, plateaued until 2010 and decreased to 2790 in 2014. CONCLUSIONS: The burden of HCV-related liver disease has increased markedly. Although the proportion diagnosed was high, treatment uptake remained low, with no increase over the last 7 years. Reducing the HCV burden in Australia requires scale-up of interferon free HCV therapies. PMID- 27197715 TI - Genetically Directed Production of Recombinant, Isosteric and Nonhydrolysable Ubiquitin Conjugates. AB - We describe the genetically directed incorporation of aminooxy functionality into recombinant proteins by using a mutant Methanosarcina barkeri pyrrolysyl-tRNA synthetase/tRNACUA pair. This allows the general production of nonhydrolysable ubiquitin conjugates of recombinant origin by bioorthogonal oxime ligation. This was exemplified by the preparation of nonhydrolysable versions of diubiquitin, polymeric ubiquitin chains and ubiquitylated SUMO. The conjugates exhibited unrivalled isostery with the native isopeptide bond, as inferred from structural and biophysical characterisation. Furthermore, the conjugates functioned as nanomolar inhibitors of deubiquitylating enzymes and were recognised by linkage specific antibodies. This technology should provide a versatile platform for the development of powerful tools for studying deubiquitylating enzymes and for elucidating the cellular roles of diverse polyubiquitin linkages. PMID- 27197718 TI - Mother's marital satisfaction associated with the quality of mother-father-child triadic interaction. AB - Low marital satisfaction has been shown to be a risk factor for early parenthood and parent-child relationship problems (Erel & Burman, ; McHale, ). The aim of this study was to assess how parental reports of marital satisfaction related to family alliance and coordination in the observed triadic interaction. The study group included 120 families. Marital satisfaction was evaluated during pregnancy, at 4 months, and at 18 months using the Revised Dyadic Adjustment Scale (RDAS; Busby, Christensen, Crane & Larsson, ) for both parents. Mother-father-child interaction was analyzed in the Lausanne Triadic Play setting and coded using the Family Alliance Assessment Scale (Favez, Lavanchy Scaiola, Tissot, Darwiche & Frascarolo, ) when the child reached 18 months of age. The mother's higher marital satisfaction at every measuring point was associated with a cooperative family alliance and/or higher family coordination at 18 months. The father's experience of marital satisfaction was not related to family interaction at any assessment point. Our study suggests that a mother's experience of lower marital satisfaction during pregnancy may be an early sign of later problems in family relationships. PMID- 27197717 TI - Gastric peroral endoscopic pyloromyotomy (G-POEM) as a salvage therapy for refractory gastroparesis: a case series of different subtypes. AB - BACKGROUND: Gastroparesis is a poorly understood, chronic, debilitating motility disorder with very limited medical therapeutic options. Gastric peroral endoscopic pyloromyotomy (G-POEM) is an emerging novel endoscopic technique as an incisionless pyloroplasty for refractory cases. Effective information of G-POEM on different types of gastroparesis is sparse. METHODS: Cases of G-POEM using selective circular myotomy as a salvage therapy for refractory symptoms were retrospective studied. The G-POEM procedures were performed by a single expert endoscopist under a certain protocol. Gastroparesis Cardinal Symptoms Index (GCSI) and gastric emptying scintigraphy (GES) were evaluated before and after the procedure. Procedures related adverse event were also recorded. KEY RESULTS: All procedures were successfully completed without complications. Each case in this series was different in demography and etiology of gastroparesis, namely postsurgical, postinfectious, and idiopathic gastroparesis in an elderly male and two young female adults. All cases were refractory to conventional treatment but demonstrated obvious success after G-POEM as a salvage therapy both clinically and on GES. CONCLUSIONS & INFERENCES: G-POEM as a salvage therapy improves symptoms and gastric emptying in patients with different types of refractory gastroparesis. Our cases are also the firsts to show success of G-POEM in postinfectious gastroparesis and in elderly male patient. More data are needed to determine which subgroup of patients would benefit most from this novel procedure. PMID- 27197720 TI - Response: Magnetic resonance lymphangiography: How to prove it? PMID- 27197719 TI - HIV-1 DNA dynamics and variations in HIV-1 DNA protease and reverse transcriptase sequences in multidrug-resistant patients during successful raltegravir-based therapy. AB - There is limited information on the variations of HIV-1 DNA mutation profile in reverse transcriptase (RT) and protease (PR) genes during suppressive antiretroviral treatment (plasma HIV-1 RNA continuously <50 copies/ml) with raltegravir (RAL)-based regimens in patients with baseline RT/PR resistant HIV. Twelve multidrug resistant (RT: 12/12, PR: 8/12) HIV-infected patients were followed during effectively suppressive RAL-based therapy. Total and integrated HIV-1 DNA were assessed by real time PCR at baseline and every 6 months. Ultrasensitive (threshold: 2.5 copies/ml) plasma HIV-1 RNA and genotypic analysis of RT and PR in proviral DNA were performed at baseline and at 24 months. Half of the patients had full viral suppression (plasma HIV-RNA < 2.5 copies/ml) at month 12. Total HIV-1 DNA declined significantly after 12 months of therapy (from 249.2 to 145.7 copies/106 cells, P = 0.023), and remained stable until 24 months, when total HIV-1 DNA levels raised, concomitantly with a less stringent suppression of HIV-1 RNA (81.8% of patients with >2.5 copies/ml). Integrated HIV-1 DNA did not show fluctuations during the study period. Sequencing of the PR and RT regions from HIV-1 DNA revealed changes in the resistance mutation profile in five patients. Total HIV-1 DNA declined after the introduction of RAL-based therapy, with a rebound after 2 years. No changes were observed in levels of integrated DNA, suggesting limited effect on archived HIV. The RT and PR sequence changes in archived HIV-1 DNA suggest that variation of the mutation profile can occur even in the absence of detectable HIV-1 RNA. J. Med. Virol. 88:2115-2124, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27197721 TI - Flexible Rechargeable Zinc-Air Batteries through Morphological Emulation of Human Hair Array. AB - An electrically rechargeable, nanoarchitectured air electrode that morphologically emulates a human hair array is demonstrated in a zinc-air battery. The hair-like array of mesoporous cobalt oxide nanopetals in nitrogen doped carbon nanotubes is grown directly on a stainless-steel mesh. This electrode produces both flexibility and improved battery performance, and thus fully manifests the advantages of flexible rechargeable zinc-air batteries in practical applications. PMID- 27197722 TI - A Study on Intraspecific Resource Partitioning in the Stingless bee Scaptotrigona mexicana Guerin (Apidae, Meliponini) Using Behavioral and Molecular Techniques. AB - As a general rule, within an ecological guild, there is one species that is dominant and is commonly the most abundant. The aim of this work was to investigate if such pattern occurs intraspecifically, among colonies of the stingless bee Scaptotrigona mexicana Guerin. Through behavioral and molecular techniques, we found preliminary evidence that apparently colonies of this species do not monopolize resources, instead they seem to share food; however, some colonies had more foragers in a food patch or in a feeder, so some type of exclusion could be at work, though we could not determine the final output of such interaction, i.e., if underrepresented colonies were eventually excluded, developed slower or were overrepresented in other food patches. Our results give evidence that resource partitioning within this species occurs peacefully; however, further studies are necessary to determine if threatening behavior or aggressions appear when resources are scarce and competition becomes harsher. PMID- 27197723 TI - New potential humic acid stationary phase toward drug components: Development of a chemometric-assisted RP-HPLC method for the determination of paracetamol and caffeine in tablet formulations. AB - A new humic acid based stationary phase has been used, for the first time, to achieve the separation and quantification of paracetamol and caffeine in pharmaceutical preparations under reversed-phase high-performance liquid chromatography conditions. Central composite design was applied as a powerful tool to optimize the most dominant parameters that influence the resolution of reversed-phase high-performance liquid chromatography, that is, mobile phase composition (acetonitrile percentage in water), flow rate, and column temperature. The optimum conditions were obtained as 21.69%, 1.5 mL/min, and 15 degrees C, respectively, with the aid of a second-order quadratic model and desirability function. Under the optimum conditions, the peaks could be baseline separated within 10 min. For the developed reversed-phase high-performance liquid chromatography method, the linearity was investigated in the concentration ranges of 2-160 mg/mL (R(2) = 0.999) for paracetamol and 2-9.9 mg/mL (R(2) = 0.991) for caffeine. Mean recoveries for paracetamol and caffeine were 95.90 and 95.68%, respectively. The limits of detection and quantification were 4.1 * 10(-4) and 1.3 * 10(-3) mg/mL for paracetamol and 1.6 * 10(-4) and 5.0 * 10(-4) mg/mL for caffeine. The results showed that the new humic acid based stationary phase is very suitable for the separation of paracetamol and caffeine in pharmaceutical preparations and, thus it can be used effectively in the pharmaceutical industry. PMID- 27197724 TI - Differences in the distribution of stroke subtypes in a UK black stroke population - final results from the South London Ethnicity and Stroke Study. AB - BACKGROUND: Stroke incidence is increased in Black individuals but the reasons for this are poorly understood. Exploring the differences in aetiological stroke subtypes, and the extent to which they are explained by conventional and novel risk factors, is an important step in elucidating the underlying mechanisms for this increased stroke risk. METHODS: Between 1999 and 2010, 1200 black and 1200 white stroke patients were prospectively recruited from a contiguous geographical area in South London in the UK. The Trial of Org 10172 (TOAST) classification was used to classify stroke subtype. Age- and sex-adjusted comparisons of socio demographics, traditional vascular risk factors and stroke subtypes were performed between black and white stroke patients and between Black Caribbean and Black African stroke patients using age-, sex-, and social deprivation-adjusted univariable and multivariable logistic regression analyses. RESULTS: Black stroke patients were younger than white stroke patients (mean (SD) 65.1 (13.7) vs. 74.8 (13.7) years). There were significant differences in the distribution of stroke subtypes. Small vessel disease stroke was increased in black patients versus white patients (27 % vs. 12 %; OR, 2.74; 95 % CI, 2.19-3.44), whereas large vessel and cardioembolic stroke was less frequent in black patients (OR, 0.59; 95 % CI, 0.45-0.78 and OR, 0.61; 95 % CI, 0.50-0.74, respectively). These associations remained after controlling for traditional vascular risk factors and socio-demographics. Black Caribbean patients appeared to have an intermediate risk factor and stroke subtype profile between that found in Black African and white stroke patients. Cardioembolic stroke was more strongly associated with Black Caribbean ethnicity versus Black African ethnicity (OR, 1.48; 95 % CI, 1.04 2.10), whereas intracranial large vessel disease was less frequent in Black Caribbean patients versus Black African subjects (OR, 0.44; 95 % CI, 0.24-0.83). CONCLUSIONS: Clear differences exist in stroke subtype distribution between black and white stroke patients, with a marked increase in small vessel stroke. These could not be explained by differences in the assessed traditional risk factors. Possible explanations for these differences might include variations in genetic susceptibility, differing rates of control of vascular risk factors, or as yet undetermined environmental risk factors. PMID- 27197725 TI - A wide spectrum of fastidious and ampicillin-susceptible bacteria dominate in animal-caused wounds. AB - The main purpose of this study was to assess the actual occurrence of Gram negative oxidase-positive bacteria (GNOP) in human wounds caused by animals, mostly cat and dog bites and scratches, and with signs of infection. We report a prospective series of 92 wound samples. Routine culturing was combined with a procedure optimised for fastidious GNOP. All GNOP isolates were identified by 16S rDNA sequencing to the species level. We observed a more prominent role of GNOP, including at least 30 species mostly in the families Flavobacteriaceae, Neisseriaceae and Pasteurellaceae, and less of Staphylococcus aureus and streptococci. The antibiotic susceptibility pattern was investigated, as GNOP are associated with sudden onset of serious infections, making an early decision on antibiotic treatment vital. All GNOP isolates judged to be clinically relevant displayed susceptibility to ampicillin and meropenem, but resistance to oxacillin, clindamycin and gentamicin was frequent. Our findings emphasise the need to cover GNOP as recommended in guidelines, and not only common wound pathogens, when treating an animal-caused wound. PMID- 27197726 TI - External validation of a PCA-3-based nomogram for predicting prostate cancer and high-grade cancer on initial prostate biopsy. AB - INTRODUCTION: The aim of this study was to externally validate a previously developed PCA3-based nomogram for the prediction of prostate cancer (PCa) and high-grade (intermediate and/or high-grade) prostate cancer (HGPCa) at the time of initial prostate biopsy. METHODS: A retrospective review was performed on a cohort of 336 men from a large urban academic medical center. All men had serum PSA <20 ng/ml and underwent initial transrectal ultrasound-guided prostate biopsy with at least 10 cores sampling for suspicious exam and/or elevated PSA. Covariates were collected for the nomogram and included age, ethnicity, family history (FH) of PCa, PSA at diagnosis, PCA3, total prostate volume (TPV), and abnormal finding on digital rectal exam (DRE). These variables were used to test the accuracy (concordance index) and calibration of a previously published PCA3 nomogram. RESULTS: Biopsy confirms PCa and HGPCa in 51.0% and 30.4% of validation patients, respectively. This differed from the original cohort in that it had significantly more PCa and HGPCA (51% vs. 44%, P = 0.019; and 30.4% vs. 19.1%, P < 0.001). Despite the differences in PCa detection the concordance index was 75% and 77% for overall PCa and HGPCa, respectively. Calibration for overall PCa was good. CONCLUSIONS: This represents the first external validation of a PCA3-based prostate cancer predictive nomogram in a North American population. Prostate 76:1019-1023, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27197727 TI - Role of worry in patients with chronic tinnitus and sensorineural hearing loss: a preliminary study. AB - Tinnitus-related distress appears to be more strongly associated with multiple psychological factors than with any perceptual properties of tinnitus. Prior studies have not investigated the role of worry in tinnitus sufferers. Worry is a dispositional cognitive trait that involves a pervasive, non-specific, future oriented proneness to fretting, which can foster negative affective states and catastrophic thinking about a specific trouble when the trouble is actual and present. We examined the relationship between worry and self-perceived anxiety and depressive symptoms and handicap in 54 outpatients with chronic tinnitus and sensorineural hearing loss who had been previously recruited for a randomized double-blind study on the efficacy of transmeatal low-level laser therapy for tinnitus. We measured the current anxiety and depressive symptoms with the State Trait Anxiety Inventory Form Y-1/Self-evaluation Depression Scale, the handicap with the Tinnitus Handicap Inventory, and the proneness to worry with the Penn State Worry Questionnaire. For the psychoacoustic tinnitus measures, we considered the loudness match and the minimum masking level. We found that tinnitus-related anxiety and depressive symptoms and handicap were significantly associated with proneness to worry (linear regression models, p < 0.01), whereas no associations were found with the psychoacoustic measures. This suggests the usefulness of worry assessment when managing chronic tinnitus in clinical practice. Early therapeutic interventions for reducing proneness to worry may facilitate better adaptation to tinnitus. PMID- 27197728 TI - Combined microscopy and molecular analyses show phloem occlusions and cell wall modifications in tomato leaves in response to 'Candidatus Phytoplasma solani'. AB - Callose deposition, phloem-protein conformational changes and cell wall thickening are calcium-mediated occlusions occurring in the plant sieve elements in response to different biotic and abiotic stresses. However, the significance of these structures in plant-phytoplasma interactions requires in-depth investigations. We adopted a novel integrated approach, based on the combined use of microscopic and molecular analyses, to investigate the structural modifications induced in tomato leaf tissues in presence of phytoplasmas, focusing on vascular bundles and on the occlusion structures. Phloem hyperplasia and string-like arrangement of xylem vessels were found in infected vascular tissue. The diverse occlusion structures were differentially modulated in the phloem in response to phytoplasma infection. Callose amount was higher in midribs from infected plants than in healthy ones. Callose was observed at sieve plates but not at pore-plasmodesma units. A putative callose synthase gene encoding a protein with high similarity to Arabidopsis CalS7, responsible for callose deposition at sieve plates, was upregulated in symptomatic leaves, indicating a modulation in the response to stolbur infection. P-proteins showed configuration changes in infected sieve elements, exhibiting condensation of the filaments. The transcripts for a putative P-protein 2 and a sieve element occlusion-related protein were localized in the phloem but only the first one was modulated in the infected tissues. PMID- 27197729 TI - Diversity of culturable Gram-negative bacteria isolated from irrigation water of two rice crop regions in Southern Brazil. AB - In this study, we assessed the diversity of Gram-negative bacteria found in water used for irrigation of rice crops in two growing areas of southern Brazil. Samples were collected from the main irrigation channel and field drain area. Twenty-two bacterial species were found in Cachoeirinha and 28 in Camaqua. In both areas, the most frequent bacterial families were Enterobacteriaceae and Aeromonadaceae. Differences in microbial diversity were observed in both study areas. Thirty-five Gram-negative species were identified; however, only 15 were common in both locations. In addition, there were found pathogenic and drug resistant species, such as Acinetobacter sp., Brucella spp., and Chryseobacterium meningosepticum. This study demonstrates the existence of a number of pathogenic species in aquatic ecosystems analyzed in three consecutive crop years, especially water used for rice production. PMID- 27197731 TI - Very low doses of direct intravenous iron in each session as maintenance therapy in hemodialysis patients. AB - BACKGROUND: Intravenous (IV) iron supplementation is widely used in hemodialysis (HD) patients to treat their periodic losses. However, the ideal dose and frequency is unknown. The goal of the study is to see if a 20 mg dose of iron IV at the end of each session of HD as iron maintenance is better than the iron prior therapy. We analyze the erythropoiesis activity (EA) and functional iron (FI) after four weeks of treatment. METHODS: In 36 patients, we measure reticulocyte count and content of hemoglobin reticulocyte (CHr) as EA and FI markers, respectively, before and after the treatment. Before the study, 23 patients received another different therapy with IV iron as maintenance therapy. RESULTS: Reticulocyte count: 49.7 +/- 23.8 * 10(3) before and 47.2 +/- 17.2 * 10(3) after the treatment (p= 0.51). The CHr: 34.8 +/- 3.7 pg and 34.4 +/- 3.5 pg, respectively, (p= 0.35), showing an excellent correlation with the other FI markers (serum iron r = 0.6; p = 0.001; saturation transferrin r = 0.49; p = 0.004); that is not shown with the serum ferritin (r = 0.23; p = 0.192) or the hepcidin levels (r = 0.22; p = 0.251). There was not a correlation between the C Reactive Protein, reticulocyte count, and CHr. The 13 patients who did not receive the iron prior to the study showed high FI levels, but not an increased of the serum ferritin or the serum hepcidin levels. CONCLUSIONS: The administration of a small quantity of iron at the end of every HD session keeps the EA and the FI levels and allows reducing the iron overload administered and/or decreasing the iron stores markers in some patients. PMID- 27197730 TI - Metabolomic Response of Skeletal Muscle to Aerobic Exercise Training in Insulin Resistant Type 1 Diabetic Rats. AB - The etiology of insulin resistance in Type 1 Diabetes (T1D) is unknown, however it affects approximately 20% of T1D patients. Intramyocellular lipids (IMCL) have been identified as a mechanism of insulin resistance. We examined skeletal muscle of T1D rats to determine if alterations in lipid metabolism were evident and whether aerobic exercise training improves IMCL and insulin resistance. To do so, 48 male Sprague-Dawley rats were divided into control (C), sedentary diabetes (D) and diabetes exercise (DX) groups. Following multiple low-dose Streptozotocin (STZ) injections (20 mg/kg), glycemia (9-15 mM) was maintained using insulin treatment. DX were treadmill trained at high intensity (~75% V02max; 5days/week) for 10 weeks. The results demonstrate that D exhibited insulin resistance compared with C and DX, indicated by decreased glucose infusion rate during a hyperinsulinemic-euglycemic clamp (p < 0.05). There were no differences between C and DX, suggesting that exercise improved insulin resistance (p < 0.05). Metabolomics analysis revealed a significant shift in lipid metabolism whereby notable fatty acid metabolites (arachidonic acid, palmitic acid and several polyunsaturated fatty acids) were significantly elevated in D compared to C and DX. Based on the intermediates observed, insulin resistance in T1D is characterized by an insulin-desensitizing intramyocellular fatty acid metabolite profile that is ameliorated with exercise training. PMID- 27197732 TI - Multiplexed CRISPR/Cas9- and TAR-Mediated Promoter Engineering of Natural Product Biosynthetic Gene Clusters in Yeast. AB - The use of DNA sequencing to guide the discovery of natural products has emerged as a new paradigm for revealing chemistries encoded in bacterial genomes. A major obstacle to implementing this approach to natural product discovery is the transcriptional silence of biosynthetic gene clusters under laboratory growth conditions. Here we describe an improved yeast-based promoter engineering platform (mCRISTAR) that combines CRISPR/Cas9 and TAR to enable single-marker multiplexed promoter engineering of large gene clusters. mCRISTAR highlights the first application of the CRISPR/Cas9 system to multiplexed promoter engineering of natural product biosynthetic gene clusters. In this method, CRISPR/Cas9 is used to induce DNA double-strand breaks in promoter regions of biosynthetic gene clusters, and the resulting operon fragments are reassembled by TAR using synthetic gene-cluster-specific promoter cassettes. mCRISTAR uses a CRISPR array to simplify the construction of a CRISPR plasmid for multiplex CRISPR and a single auxotrophic selection to improve the inefficiency of using a CRISPR array for multiplex gene cluster refactoring. mCRISTAR is a simple and generic method for multiplexed replacement of promoters in biosynthetic gene clusters that will facilitate the discovery of natural products from the rapidly growing collection of gene clusters found in microbial genome and metagenome sequencing projects. PMID- 27197733 TI - Response to Wise et al. (Tiotropium safety in real life populations). PMID- 27197734 TI - Genetically Modified Organisms and the Future Global Nutrient Supply: Part of the Solution or a New Problem? AB - For almost a generation now, scientists and policy makers have enthusiastically advanced genetically modified (GM) crops as a solution to both global food security and, specifically, the micronutrient needs of the hidden hungry. While genetic modification offers the prospect of overcoming technological barriers to food security, the gap between the vision and reality remains large. This chapter examines the impact of GM crops at three levels. Undoubtedly, at the micro level, bio-fortification offers a real opportunity to enhance the availability of micronutrients. However, the inexorable 'research sieve' ruthlessly culls most technical candidates in the agri-food system. GM bio-fortified foods, such as Golden RiceTM, remain only a promise. At the meso level, GM crops have generated benefits for both producers and consumers who have adopted GM crops, but given that the technology has been differentially applied to maize, the average diet for the food insecure has become somewhat less balanced. Finally, while GM crops have increased yields and the global food supply, these have come at the cost of more complex and costly trade and market systems, which impair access and availability. In essence, while biotechnology offers some tantalizing technological prospects, the difficulties of getting the corresponding benefits to the most needy have dampened some of the enthusiasm. PMID- 27197735 TI - A Mixed-Method Assessment of a New Supermarket in a Food Desert: Contributions to Everyday Life and Health. AB - Initiatives to build supermarkets in low-income areas with relatively poor access to large food retailers ("food deserts") have been implemented at all levels of government, although evaluative studies have not found these projects to improve diet or weight status for shoppers. Though known to be influential, existing evaluations have neglected in-store social dynamics and shopper behaviors. Surveys and walking interviews were used with shoppers (n = 32) at a supermarket developed through the Pennsylvania Fresh Food Financing Initiative in Philadelphia, PA. Key informant interviews with stakeholders in the supermarket's development and operations provided additional context to these shopper experiences. Data were collected in July and September 2014 and qualitatively analyzed in NVivo 10.0. Participants described how the retailer helped them adapt or cope with difficult shopping routines and how it presented a reliable high quality option (in terms of cleanliness, orderliness, and social atmosphere) in contrast to other neighborhood retailers. Health concerns were also identified, especially among those managing chronic disease for themselves or a family member. These issues underscored multiple points of challenge required to adjust shopping and eating behavior. In-store supports that reflect these challenges are warranted to more fully address food deserts and reduce health disparities. PMID- 27197737 TI - Critical Dietary Habits in Early Childhood: Principles and Practice. AB - The adequacy of a diet is usually evaluated based on nutrient intake. As people eat foods but not nutrients, food-based dietary guidelines (FBDG) are needed. To evaluate dietary habits in infants and young children, the following stepwise approach is suggested: (1) develop country-specific FBDG to identify the potential of common nonfortified foods to ensure adequate nutrient intake and (2) examine potential 'critical' dietary patterns if main food groups are excluded, such as in vegetarian diets or if a family's precarious social status leads to food constraints. The German FBDG for infant and child nutrition demonstrate that a well-designed mixture of common foods results in an adequate supply of nutrients, except for vitamin D, iodine and iron. The following solutions are feasible to address deficiencies in these critical nutrients: routine supplementation (vitamin D), fortified complementary food consumption or supplementation for infants as well as inclusion of table salt in the family diet for children (iodine), and individual pediatric care for infants at risk (iron). In the exclusion of food groups of animal origin from vegetarian diets, several nutrients are at risk of becoming deficient if not substituted. Existing studies characterizing vegetarian children are rare. These were mainly published in the 1980s and 1990s and were biased towards a high social status. Thus, firm conclusions on today's dietary practices and health statuses of European vegetarian children cannot be drawn. A social gradient exists for food patterns and dietary quality in children, but energy intake need not necessarily be affected. Scenarios in Germany suggest that families on unemployment assistance can afford to eat a diet compliant with German FBDG only if they restrict food selection to basic food. Yet, the question of how families cope with financial constraints in everyday life remains. In conclusion, well-designed FBDG provide various opportunities to identify critical nutrients and critical food habits in early childhood and beyond. PMID- 27197736 TI - Spatializing Area-Based Measures of Neighborhood Characteristics for Multilevel Regression Analyses: An Areal Median Filtering Approach. AB - Area-based measures of neighborhood characteristics simply derived from enumeration units (e.g., census tracts or block groups) ignore the potential of spatial spillover effects, and thus incorporating such measures into multilevel regression models may underestimate the neighborhood effects on health. To overcome this limitation, we describe the concept and method of areal median filtering to spatialize area-based measures of neighborhood characteristics for multilevel regression analyses. The areal median filtering approach provides a means to specify or formulate "neighborhoods" as meaningful geographic entities by removing enumeration unit boundaries as the absolute barriers and by pooling information from the neighboring enumeration units. This spatializing process takes into account for the potential of spatial spillover effects and also converts aspatial measures of neighborhood characteristics into spatial measures. From a conceptual and methodological standpoint, incorporating the derived spatial measures into multilevel regression analyses allows us to more accurately examine the relationships between neighborhood characteristics and health. To promote and set the stage for informative research in the future, we provide a few important conceptual and methodological remarks, and discuss possible applications, inherent limitations, and practical solutions for using the areal median filtering approach in the study of neighborhood effects on health. PMID- 27197738 TI - Stimulation of Eryptosis, the Suicidal Erythrocyte Death by Piceatannol. AB - BACKGROUND/AIMS: Piceatannol, an analog and metabolite of resveratrol, is effective against various disorders including malignancy. It is in part effective by triggering suicidal death or apoptosis of tumor cells. Cellular mechanisms mediating the proapoptotic effect of Piceatannol include mitochondrial depolarization and cytochrome c release. Erythrocytes lack mitochondria but may nevertheless enter suicidal death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Cellular mechanisms involved in the triggering of eryptosis include increase of cytosolic Ca2+ activity ([Ca2+]i), oxidative stress and ceramide formation. The present study explored, whether Piceatannol induces eryptosis and, if so, to shed some light on the cellular mechanisms involved. METHODS: Phosphatidylserine exposure at the cell surface was estimated from annexin-V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3 fluorescence, reactive oxygen species (ROS) formation from 2',7' dichlorodihydrofluorescein (DCF) diacetate-dependent fluorescence, and ceramide abundance utilizing specific antibodies. Hemoglobin concentration in the supernatant was taken as measure of hemolysis. RESULTS: A 48 hours exposure of human erythrocytes to Piceatannol (10 - 20 uM) significantly increased the percentage of annexin-V-binding cells, significantly decreased forward scatter, significantly increased DCFDA-fluorescence, significantly increased ceramide abundance, but did not significantly increase Fluo3-fluorescence. Removal of extracellular Ca2+ slightly blunted but did not abolish the effect of Piceatannol on annexin-V-binding and forward scatter. Piceatannol (20 uM) significantly augmented the increase of annexin-V-binding, but significantly blunted the decrease of forward scatter following treatment with the Ca2+ ionophore ionomycin. CONCLUSIONS: Piceatannol triggers cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect at least in part downstream of Ca2+ and involving oxidative stress and ceramide formation. PMID- 27197739 TI - Thulium Vaporesection of the Prostate and Thulium Vapoenucleation of the Prostate in Patients on Oral Anticoagulants: A Retrospective Three-Centre Matched-Paired Comparison. AB - INTRODUCTION: To evaluate the short-term results of thulium vaporesection of the prostate (ThuVEP) and thulium vapoenucleation of the prostate (ThuVARP) in patients with benign prostatic obstruction on oral anticoagulants (OA). METHODS: A 3-centre retrospective matched-paired comparison of patients treated by ThuVEP (n = 26) or ThuVARP (n = 26) was performed. Thirty-four patients were on aspirin/ticlopidin, 7 on clopidogrel or clopidogrel and aspirin, and 11 on phenprocoumon at the time of surgery. RESULTS: Haemoglobin decrease was higher after ThuVEP compared to ThuVARP (1.5 vs. 0.3 g/dl, p < 0.001). The rate of postoperative blood transfusions (3.9 vs. 0%), clot retention (3.9 vs. 0%), and re-operation (7.7 vs. 0%) was not different between ThuVEP and ThuVARP (p = 0.274). Catheterization time was shorter for ThuVARP (1 vs. 2 days, p < 0.01). Qmax was significantly higher after ThuVEP at 6-month follow-up (31 vs. 21.5 ml/s, p < 0.001), while improvements in International Prostate Symptom Score, quality of life, and post-voiding residual urine showed no differences between the groups. Urethral or bladder neck strictures did not occur during the 6-month follow-up in both groups. CONCLUSIONS: ThuVEP and ThuVARP are safe and efficacious procedures in patients on OA. Although patients assigned to ThuVEP had higher Qmax at 6-month follow-up, ThuVARP resulted in similar functional outcomes. PMID- 27197741 TI - High Efficiency Inverted Organic Solar Cells with a Neutral Fulleropyrrolidine Electron-Collecting Interlayer. AB - A novel fulleropyrrolidine derivative, named FPNOH, was designed, synthesized, and utilized as an efficient electron-collecting (EC) layer for inverted organic solar cells (i-OSCs). The grafted diethanolamino-polar moieties can not only trigger its function as an EC interlayer, but also induce orthogonal solubility that guarantees subsequent multilayer processing without interfacial mixing. A higher power conversion efficiency (PCE) value of 8.34% was achieved for i-OSC devices with ITO/FPNOH EC electrode, compared to that of the sol-gel ZnO based reference devices with an optimized PCE value of 7.92%. High efficiency exceeding 7.7% was still achieved even for the devices with a relatively thick FPNOH film (16.9 nm). It is worthwhile to mention that this kind of material exhibits less thickness dependent performance, in contrast to widely utilized p-type conjugated polyelectrolytes (CPEs) as well as the nonconjugated polyelectrolytes (NCPEs). Further investigation on illuminating intensity dependent parameters revealed the role of FPNOH in reducing interfacial trap-induced recombination at the ITO/active layer interface. PMID- 27197740 TI - Age-period-cohort analysis of smoking prevalence among young adults in Korea. AB - OBJECTIVES: Smoking prevalence among Korean men in their thirties is substantially high (approximately 50%). An in-depth analysis of smoking trends among young adults in their twenties is necessary to devise antismoking policies for the next 10 years. This study aimed to identify the contributions of age, period, and birth cohort effects on smoking prevalence in young adults. METHODS: Subjects comprised 181,136 adults (83,947 men: 46.3%; 97,189 women: 53.7%) aged 19 to 30 years from the 2008-2013 Korea Community Health Survey. Smoking prevalence adjusted with reference to the 2008 population was applied to the age period-cohort (APC) model to identify the independent effects of each factor. RESULTS: For men, smoking prevalence rapidly escalated among subjects aged 19 to 22 years and slowed down among those aged 23 to 30 years, declined during 2008 to 2010 but stabilized during 2011 to 2013, and declined in birth cohorts prior to 1988 but stabilized in subjects born after 1988. However, in APC models, smoking prevalence increased with age in the 1988 to 1991 birth cohort. In this birth cohort, smoking prevalence at age 19 to 20 years was approximately 24% but increased to 40% when the subjects turned 23 to 24 years. For women, smoking prevalence was too low to generate consistent results. CONCLUSIONS: Over the past six years and in recent birth cohorts, smoking prevalence in adults aged 19 to 30 years has declined and is stable. Smoking prevalence should be more closely followed as it remains susceptible to an increase depending on antismoking policies or social conditions. PMID- 27197742 TI - Establishing a design for passive vertical flow constructed wetlands treating small sewage discharges to meet British Standard EN 12566. AB - Owing to legislation change (which made General Binding Rules effective from 1 January 2015) unless discharge is to specified environmentally sensitive sites, small sewage discharges (SSDs) in England - that is, <2 m3 d-1 to ground; <5 m3 d 1 to surface waters - no longer require an Environmental Permit (EP) and need not be registered for exemption, provided discharge to surface waters is preceded by treatment using equipment complying with BS EN 12566. This effectively excludes the use of treatment wetlands, unless covered by an EP, because the cost of certification to EN 12566 for bespoke designs is prohibitive. EPs take up to four months to obtain. Therefore, the new legislation has created a commercial disadvantage for constructed wetlands treating SSDs, compared with mass-produced sewage treatment plants. However, the UK statutory pollution regulators have maintained a dialogue with the Constructed Wetland Association (CWA), with a view to assessing whether treatment of SSD using constructed wetlands might be allowable, without requiring EPs. This paper presents treatment performance data obtained over 15 years, from a variety of full-scale operational treatment wetlands, as supporting evidence for design guidelines, proposed by the CWA to the UK regulators, for the implementation of constructed wetlands continuously passively treating SSD to 20:30:20 mg l-1 BOD/SS/NH4-N under a wide range of loading rates. Relevant experience of UK designers, installers and operators since the early 1990s is included, resulting in recommended physical design criteria and loading rates for compact vertical flow reed beds, presented here as key elements of the draft guidelines. PMID- 27197743 TI - Treatment of focal benign lesions of the bone: MRgFUS and RFA. AB - The objective of this study was to evaluate the role of MR-guided focused ultrasound surgery and radiofrequency ablation in the management of bone and soft tissue lesions. Musculoskeletal interventional radiology represents an interesting option for the treatment of benign bone and soft-tissue lesions to avoid the invasiveness of surgery and related risks. The imaging techniques now available, besides representing an optimal guide, allow control of the temperature reached in the region of interest, avoiding or minimizing damage to the sensitive structures surrounding the lesion. PMID- 27197744 TI - Intravoxel incoherent motion diffusion-weighted MR imaging of breast cancer: association with histopathological features and subtypes. AB - OBJECTIVE: To evaluate the associations between intravoxel incoherent motion (IVIM)-derived parameters and histopathological features and subtypes of breast cancer. METHODS: Pre-operative MRI from 275 patients with unilateral breast cancer was analyzed. The apparent diffusion coefficient (ADC) and IVIM parameters [tissue diffusion coefficient (Dt), perfusion fraction (fp) and pseudodiffusion coefficient] were obtained from cancer and normal tissue using diffusion-weighted imaging with b-values of 0, 30, 70, 100, 150, 200, 300, 400, 500 and 800 s mm( 2). We then compared the IVIM parameters of tumours with different histopathological features and subtypes. RESULTS: The ADC and Dt were lower and fp was higher in cancers than in normal tissues (p < 0.001). The Dt was lower in high Ki-67 cancer than in low Ki-67 cancer (p = 0.019), whereas ADC showed no significant difference (p = 0.309). Luminal B [human epidermal growth factor receptor 2 (HER2)-negative] cancer showed lower ADC (p = 0.003) and Dt (p = 0.001) than other types. CONCLUSION: We found low tissue diffusivity in high Ki 67 cancer and luminal B (HER2-negative) cancer using IVIM imaging. ADVANCES IN KNOWLEDGE: Low tissue diffusivity is more clearly shown in high Ki-67 tumours and luminal B (HER2-negative) tumours with the IVIM model. PMID- 27197746 TI - Caregiver talk to young Spanish-English bilinguals: comparing direct observation and parent-report measures of dual-language exposure. AB - In research on language development by bilingual children, the early language environment is commonly characterized in terms of the relative amount of exposure a child gets to each language based on parent report. Little is known about how absolute measures of child-directed speech in two languages relate to language growth. In this study of 3-year-old Spanish-English bilinguals (n = 18), traditional parent-report estimates of exposure were compared to measures of the number of Spanish and English words children heard during naturalistic audio recordings. While the two estimates were moderately correlated, observed numbers of child-directed words were more consistently predictive of children's processing speed and standardized test performance, even when controlling for reported proportion of exposure. These findings highlight the importance of caregiver engagement in bilingual children's language outcomes in both of the languages they are learning. PMID- 27197748 TI - Global life expectancy increases by five years. PMID- 27197745 TI - Hepatocyte nuclear factor 1alpha-inactivated hepatocellular adenomas exhibit high (18)F-fludeoxyglucose uptake associated with glucose-6-phosphate transporter inactivation. AB - OBJECTIVE: This immunohistochemical study aimed to elucidate the molecular mechanism underlying the increased fluorine-18 fludeoxyglucose (FDG) uptake in hepatocyte nuclear factor 1alpha (HNF1alpha)-inactivated hepatocellular adenomas (H-HCAs). METHODS: Three resected H-HCAs were studied using FDG positron emission tomography. Each maximum standardized uptake value (SUVmax) was determined. Resected samples were subjected to immunohistochemical staining for the following glucose metabolism-related proteins: glucose transporter 1 (GLUT1) and glucose transporter 2 (GLUT2), indicative of uptake and transport of glucose into cellular cytoplasm; hexokinase 2 (HK2) and hexokinase 4 (HK4), glucose phosphorylation; glucose-6-phosphate transporter 1 (G6PT1), uptake and transport of glucose-6-phosphate into endoplasmic reticulum; and glucose-6-phosphatase (G6Pase), dephosphorylation. RESULTS: All three H-HCAs exhibited increased FDG intake, with an average SUVmax of 6.6 (range: 5.2-8.2). No sample expressed GLUT1 and HK2; all the samples exhibited equivalent GLUT2 and HK4 expression, equivalent or slightly increased G6Pase expression and significantly decreased G6PT1 expression relative to the non-neoplastic hepatocytes of background liver. CONCLUSION: The increased FDG uptake observed in H-HCAs is associated with GLUT2 and HK4 expression and G6PT1 inactivation. ADVANCES IN KNOWLEDGE: H-HCA exhibits a high FDG uptake owing to the inactivation of G6PT1, which is transcriptionally regulated by HNF1alpha. PMID- 27197747 TI - The combined effects of soya isoflavones and resistant starch on equol production and trabecular bone loss in ovariectomised mice. AB - Equol is a metabolite of the soya isoflavone (ISO) daidzein that is produced by intestinal microbiota. Equol has greater oestrogenic activity compared with other ISO, and it prevents bone loss in postmenopausal women. Resistant starch (RS), which has a prebiotic activity and is a dietary fibre, was reported to promote equol production. Conversely, the intestinal microbiota is reported to directly regulate bone health by reducing inflammatory cytokine levels and T-lymphocytes in bone. The present study evaluated the combined effects of diet supplemented with ISO and RS on intestinal microbiota, equol production, bone mineral density (BMD) and inflammatory gene expression in the bone marrow of ovariectomised (OVX) mice. Female ddY strain mice, aged 8 weeks, were either sham-operated (Sham, n 7) or OVX. OVX mice were randomly divided into the following four groups (seven per group): OVX control (OVX); OVX fed 0.05 % ISO diet (OVX+ISO); OVX fed 9 % RS diet (OVX+RS); and OVX fed 0.05 % ISO- and 9 % RS diet (OVX+ISO+RS). After 6 weeks, treatment with the combination of ISO and RS increased equol production, prevented the OVX-induced decline in trabecular BMD in the distal femur by modulating the enteric environment and altered OVX-induced inflammation-related gene expression in the bone marrow. However, there were no significant differences in bone parameters between the ISO+RS and ISO-alone groups in OVX mice. Our findings suggest that the combination of ISO and RS might alter intestinal microbiota and immune status in the bone marrow, resulting in attenuated bone resorption in OVX mice. PMID- 27197750 TI - Fragment molecular orbital study of the cAMP-dependent protein kinase catalyzed phosphoryl transfer: a comparison with the differential transition state stabilization method. AB - The importance of key residues to the activity of the cAMP-dependent protein kinase catalyzed phosphoryl transfer and to the stabilization of the transition state of the reaction has been investigated by means of the fragment molecular orbital (FMO) method. To evaluate the accuracy of the method and its capability of fragmenting covalent bonds, we have compared stabilization energies due to the interactions between individual residues and the reaction center to results obtained with the differential transition state stabilization method (Szarek, et al., J. Phys. Chem. B, 2008, 112, 11819-11826) and observe, despite a size difference in the fragment describing the reaction center, near-quantitative agreement. We have also computed deletion energies to investigate the effect of virtual deletion of key residues on the activation energy. These results are consistent with the stabilization energies and yield additional information as they clearly capture the effect of secondary interactions, i.e. interactions in the second coordination layer of the reaction center. We find that using FMO to calculate deletion energies is a powerful and time efficient approach to analyze the importance of key residues to the activity of an enzyme catalyzed reaction. PMID- 27197749 TI - Bulk development and stringent selection of microsatellite markers in the western flower thrips Frankliniella occidentalis. AB - Recent improvements in next-generation sequencing technologies have enabled investigation of microsatellites on a genome-wide scale. Faced with a huge amount of candidates, the use of appropriate marker selection criteria is crucial. Here, we used the western flower thrips Frankliniella occidentalis for an empirical microsatellite survey and validation; 132,251 candidate microsatellites were identified, 92,102 of which were perfect. Dinucleotides were the most abundant category, while (AG)n was the most abundant motif. Sixty primer pairs were designed and validated in two natural populations, of which 30 loci were polymorphic, stable, and repeatable, but not all in Hardy-Weinberg equilibrium (HWE) and linkage equilibrium. Four marker panels were constructed to understand effect of marker selection on population genetic analyses: (i) only accept loci with single nucleotide insertions (SNI); (ii) only accept the most polymorphic loci (MP); (iii) only accept loci that did not deviate from HWE, did not show SNIs, and had unambiguous peaks (SS) and (iv) all developed markers (ALL). Although the MP panel resulted in microsatellites of highest genetic diversity followed by the SNI, the SS performed best in individual assignment. Our study proposes stringent criteria for selection of microsatellites from a large-scale number of genomic candidates for population genetic studies. PMID- 27197751 TI - Distribution of lymph node metastases on FDG-PET/CT in inoperable or unresectable oesophageal cancer patients and the impact on target volume definition in radiation therapy. AB - INTRODUCTION: Definitive chemoradiotherapy (dCRT) is standard care for localised inoperable/unresectable oesophageal tumours. Many surgical series have reported on distribution of lymph node metastases (LNM) in resected patients. However, no data is available on the distribution of at-risk LN regions in this more unfavourable patient group. This study aimed to determine the spread of LNM using FDG-PET/CT, to compare it with the distribution in surgical series and to define its impact on the definition of elective LN irradiation (ENI). METHODS: FDG PET/CT images of patients with oesophageal cancer treated with dCRT (from 2003 to 2013) were reviewed to identify the anatomic distribution of FDG-avid LNs. Tumours were divided according to proximal, mid-thoracic or distal localisation. RESULTS: About 105 consecutive patients entered analysis. The highest numbers of FDG-avid LNs in proximal tumours were at LN station 101R (45%) and 106recL (35%). For mid-thoracic tumours at 104R (30%) and 105 (30%). For tumours located in the distal oesophagus, the most common sites were along the lesser curvature of the stomach (21%) and the left gastric artery (21%). Except for the supraclavicular and pretracheal nodes, there were no positive locoregional LNM found outside the standard surgical resection area. CONCLUSION: Our results show a good correlation between the distribution of nodal volumes at risk in surgical series and on FDG PET/CT. The results can be used to determine target definition in dCRT for oesophageal cancer. For mid-thoracic tumours, the current target delineation guidelines may be extended based on the risk of node involvement, but more clinical studies are needed to determine if the potential harm of expanding the CTV outweighs the potential benefit. PMID- 27197752 TI - PKA-CREB-BDNF signaling regulated long lasting antidepressant activities of Yueju but not ketamine. AB - Yueju confers antidepressant effects in a rapid and long-lasting manner, similar to ketamine. CREB (cAMP-response element binding protein) signaling is implicated in depression pathology and antidepressant responses. However, the role of CREB and associated brain derived neurotrophic factor (BDNF) signaling in rapid and long-lasting antidepressant effects remains unclear. Here, we demonstrated that ICR and Kunming strain mice conferred antidepressant responses lasting for 1 and 5 days, respectively, following a single dose of Yueju. One day post Yueju in Kunming but not ICR strain mice, expression of total and phosphorylated CREB, as well as the CREB signaling activator, PKA (protein kinase A) was up-regulated in the hippocampus. Although BDNF gene expression increased at 3 hours in both strains, it remained up-regulated at 1 day only in Kunming mice. Ketamine showed similar strain-dependent behavioral effects. However, blockade of PKA/CREB signaling blunted the antidepressant effects and reversed the up-regulation of BDNF gene expression by Yueju, but not ketamine. Conversely, blockade of mammalian target of rapamycin signaling led to opposite effects. Taken altogether, prolonged transcriptional up-regulation of hippocampal BDNF may account for the stain-dependent enduring antidepressant responses to Yueju and ketamine, but it was mediated via PKA/CREB pathway only for Yueju. PMID- 27197753 TI - F-box only protein 9 is an E3 ubiquitin ligase of PPARgamma. AB - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a critical regulator of carbohydrate and lipid metabolism, adipocyte differentiation and inflammatory response. Post-translational modification of PPARgamma and its degradation involve several pathways, including the ubiquitin-proteasome system. Here, we identified F-box only protein 9 (FBXO9) as an E3 ubiquitin ligase of PPARgamma. We screened interacting partners of PPARgamma using immunoprecipitation and mass spectrometric analysis and identified FBXO9 as an E3 ubiquitin ligase of PPARgamma. FBXO9 directly interacted with PPARgamma through the activation function-1 domain and ligand-binding domain. FBXO9 decreased the protein stability of PPARgamma through induction of ubiquitination. We found that the F-box motif of FBXO9 was required for its ubiquitination function. The activity of PPARgamma was significantly decreased by FBXO9 overexpression. Furthermore, FBXO9 overexpression in 3T3-L1 adipocytes resulted in decreased levels of endogenous PPARgamma and suppression of adipogenesis. These results suggest that FBXO9 is an important enzyme that regulates the stability and activity of PPARgamma through ubiquitination. PMID- 27197755 TI - Effect of a pager notification system on Australasian Triage Scale category 2 patients in a paediatric emergency department. AB - OBJECTIVE: Australasian EDs have introduced innovative processes to ensure safe and timely management of patients. Our ED introduced a dedicated pager system to provide rapid assessment of Australasian Triage Scale (ATS) category 2 patients in an attempt to expedite ED care. The present paper aims to evaluate the impact of this initiative on time to clinician, ED length of stay (LOS) and clinical outcomes in a tertiary paediatric ED. METHODS: Retrospective structured chart review on patients presenting in a 2 month period before the intervention (August September 2009) and the same time 1 year later. Patients were grouped into common ATS category 2 presentations and analysed in these subcategories. Clinical indicators of appropriate and timely performance were selected from best practice performance guidelines. RESULTS: 779 ATS category 2 patients were seen during the two periods: 370 pre-intervention and 409 post-intervention. The overall percentage of ATS category 2 patients seen within the target time increased by 22.3%, although there was no significant change in ED LOS. The median time for patients from triage to being seen by an ED clinician improved from 10 to 6 min (P < 0.01). However, we were unable to demonstrate an impact of the pager system on various clinical quality indicators. CONCLUSIONS: The rapid assessment pager system proved beneficial in reducing triage to clinician times for ATS category 2 patients but showed no improvement in overall ED LOS or disease-specific clinical quality indicators. Further research is needed to determine the influence of other components of ED functioning on clinical outcomes, as well as the overall clinical impact a pager system has on other measures of quality such as patient satisfaction and other subgroups of patients. PMID- 27197754 TI - Adaptive evolution of complex innovations through stepwise metabolic niche expansion. AB - A central challenge in evolutionary biology concerns the mechanisms by which complex metabolic innovations requiring multiple mutations arise. Here, we propose that metabolic innovations accessible through the addition of a single reaction serve as stepping stones towards the later establishment of complex metabolic features in another environment. We demonstrate the feasibility of this hypothesis through three complementary analyses. First, using genome-scale metabolic modelling, we show that complex metabolic innovations in Escherichia coli can arise via changing nutrient conditions. Second, using phylogenetic approaches, we demonstrate that the acquisition patterns of complex metabolic pathways during the evolutionary history of bacterial genomes support the hypothesis. Third, we show how adaptation of laboratory populations of E. coli to one carbon source facilitates the later adaptation to another carbon source. Our work demonstrates how complex innovations can evolve through series of adaptive steps without the need to invoke non-adaptive processes. PMID- 27197756 TI - Neurotrophins and their Trk-receptors in the cerebellum of zebrafish. AB - Neurotrophins (NTs) and their specific Trk-receptors are key molecules involved in the regulation of survival, proliferation, and differentiation of central nervous system during development and adulthood in vertebrates. In the present survey, we studied the expression and localization of neurotrophins and their Trk receptors in the cerebellum of teleost fish Danio rerio (zebrafish). Teleostean cerebellum is composed of a valvula, body and vestibulolateral lobe. Valvula and body show the same three-layer structure as cerebellar cortex in mammals. The expression of NTs and Trk-receptors in the whole brain of zebrafish has been studied by Western blotting analysis. By immunohistochemistry, the localization of NTs has been observed mainly in Purkinje cells; TrkA and TrkB-receptors in cells and fibers of granular and molecular layers. TrkC was faintly detected. The occurrence of NTs and Trk-receptors suggests that they could have a synergistic action in the cerebellum of zebrafish. J. Morphol. 277:725-736, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27197758 TI - A systematic review of early life factors which adversely affect subsequent lung function. AB - It has been known for many years that multiple early life factors can adversely affect lung function and future respiratory health. This is the first systematic review to attempt to analyse all these factors simultaneously. We adhered to strict a priori criteria for inclusion and exclusion of studies. The initial search yielded 29,351 citations of which 208 articles were reviewed in full and 25 were included in the review. This included 6 birth cohorts and 19 longitudinal population studies. The 25 studies reported the effect of 74 childhood factors (on their own or in combinations with other factors) on subsequent lung function reported as percent predicted forced expiration in one second (FEV1). The childhood factors that were associated with a significant reduction in future FEV1 could be grouped as: early infection, bronchial hyper-reactivity (BHR) / airway lability, a diagnosis of asthma, wheeze, family history of atopy or asthma, respiratory symptoms and prematurity / low birth weight. A complete mathematical model will only be possible if the raw data from all previous studies is made available. This highlights the need for increased cooperation between researchers and the need for international consensus about the outcome measures for future longitudinal studies. PMID- 27197757 TI - Drosophila insulin-like peptide 1 (DILP1) is transiently expressed during non feeding stages and reproductive dormancy. AB - The insulin/insulin-like growth factor signaling pathway is evolutionarily conserved in animals, and is part of nutrient-sensing mechanisms that control growth, metabolism, reproduction, stress responses, and lifespan. In Drosophila, eight insulin-like peptides (DILP1-8) are known, six of which have been investigated in some detail, whereas expression and functions of DILP1 and DILP4 remain enigmatic. Here we demonstrate that dilp1/DILP1 is transiently expressed in brain insulin producing cells (IPCs) from early pupa until a few days of adult life. However, in adult female flies where diapause is triggered by low temperature and short days, within a time window 0-10h post-eclosion, the dilp1/DILP1 expression remains high for at least 9 weeks. The dilp1 mRNA level is increased in dilp2, 3, 5 and dilp6 mutant flies, indicating feedback regulation. Furthermore, the DILP1 expression in IPCs is regulated by short neuropeptide F, juvenile hormone and presence of larval adipocytes. Male dilp1 mutant flies display increased lifespan and reduced starvation resistance, whereas in female dilp1 mutants oviposition is reduced. Thus, DILP1 is expressed in non-feeding stages and in diapausing flies, is under feedback regulation and appears to play sex-specific functional roles. PMID- 27197759 TI - Independent modulations of the transmission amplitudes and phases by using Huygens metasurfaces. AB - We propose ultrathin Huygens metasurfaces to control transmission amplitudes and phases of electromagnetic waves independently, in which each unit cell is comprised of an electric dipole and a magnetic dipole. By altering the electric and magnetic responses of unit cells, arbitrary complex transmission coefficients with modulus values smaller than 0.85 are obtained. Two Huygens metasurfaces capable of controlling the diffraction orders are designed and fabricated by modulating the distributions of the complex transmission coefficients. More complicated functions such as holographic imaging can also be accomplished by using the proposed Huygens metasurfaces. PMID- 27197760 TI - Cyclization of a cell-penetrating peptide via click-chemistry increases proteolytic resistance and improves drug delivery. AB - In this work we report synthesis and biological evaluation of a cell-penetrating peptide (CPP), that is partly cyclized via a triazole bridge. Recently, beneficious properties have been reported for cyclized peptides concerning their metabolic stability and intracellular uptake. A CPP based on human calcitonin was used in this study, and side chain cyclization was achieved via copper catalyzed alkyne-azide click reaction. Cell viability studies in several cell-lines revealed no cytotoxic effects. Furthermore, efficient uptake in breast cancer MCF 7 cells could be determined. Moreover, preliminary studies using this novel peptide as drug transporter for daunorubicin were performed. Copyright (c) 2016 European Peptide Society and John Wiley & Sons, Ltd. PMID- 27197762 TI - Mass spectrometry of B. subtilis CopZ: Cu(i)-binding and interactions with bacillithiol. AB - CopZ from Bacillus subtilis is a well-studied member of the highly conserved family of Atx1-like copper chaperones. It was previously shown via solution and crystallographic studies to undergo Cu(i)-mediated dimerisation, where the CopZ dimer can bind between one and four Cu(i) ions. However, these studies could not provide information about the changing distribution of species at increasing Cu(i) levels. To address this, electrospray ionisation mass spectrometry using soft ionisation was applied to CopZ under native conditions. Data revealed folded, monomeric CopZ in apo- and Cu(i)-bound forms, along with Cu(i)-bound dimeric forms of CopZ at higher Cu(i) loading. Cu4(CopZ)2 was the major dimeric species at loadings >1 Cu(i)/CopZ, indicating the cooperative formation of the tetranuclear Cu(i)-bound species. As the principal low molecular weight thiol in B. subtilis, bacillithiol (BSH) may play a role in copper homeostasis. Mass spectrometry showed that increasing BSH led to a reduction in Cu(i)-bound dimeric forms, and the formation of S-bacillithiolated apo-CopZ and BSH adducts of Cu(i) bound forms of CopZ, where BSH likely acts as a Cu(i) ligand. These data, along with the high affinity of BSH for Cu(i), determined here to be beta2(BSH) = ~4 * 10(17) M(-2), are consistent with a role for BSH alongside CopZ in buffering cellular Cu(i) levels. Here, mass spectrometry provides a high resolution overview of CopZ-Cu(i) speciation that cannot be obtained from less discriminating solution-phase methods, thus illustrating the potential for the wider application of this technique to studies of metal-protein interactions. PMID- 27197763 TI - Distribution and contamination assessment of heavy metals in surface sediments of the Luanhe River Estuary, northwest of the Bohai Sea. AB - 33 surface sediment samples from the Luanhe River Estuary have been analyzed for heavy metals to evaluate the spatial distribution pattern and their potential ecological risk. Higher metal concentrations were found in the river mouth and southern areas where being covered by fine particulate matters. In comparison with the threshold effect level and the probable effect level, Cu, Pb, Cr, Ni, and As had occasionally adverse biological effects on the aquatic ecosystems. Both the enrichment factor and geoaccumulation index values show that all the regions have been weakly polluted by Pb, Hg, As, and Cd with an exception of being moderately to strongly polluted by Hg in the river mouth and southern areas. The sources of Zn, Ni, Cd, Hg, and Cr were mainly from the river input and coastal discharge, whereas Cu, Pb, and As were mainly derived from vehicle emissions, coal and oil combustion. PMID- 27197761 TI - Pseudouridine synthase 1 deficient mice, a model for Mitochondrial Myopathy with Sideroblastic Anemia, exhibit muscle morphology and physiology alterations. AB - Mitochondrial myopathy with lactic acidosis and sideroblastic anemia (MLASA) is an oxidative phosphorylation disorder, with primary clinical manifestations of myopathic exercise intolerance and a macrocytic sideroblastic anemia. One cause of MLASA is recessive mutations in PUS1, which encodes pseudouridine (Psi) synthase 1 (Pus1p). Here we describe a mouse model of MLASA due to mutations in PUS1. As expected, certain Psi modifications were missing in cytoplasmic and mitochondrial tRNAs from Pus1(-/-) animals. Pus1(-/-) mice were born at the expected Mendelian frequency and were non-dysmorphic. At 14 weeks the mutants displayed reduced exercise capacity. Examination of tibialis anterior (TA) muscle morphology and histochemistry demonstrated an increase in the cross sectional area and proportion of myosin heavy chain (MHC) IIB and low succinate dehydrogenase (SDH) expressing myofibers, without a change in the size of MHC IIA positive or high SDH myofibers. Cytochrome c oxidase activity was significantly reduced in extracts from red gastrocnemius muscle from Pus1(-/-) mice. Transmission electron microscopy on red gastrocnemius muscle demonstrated that Pus1(-/-) mice also had lower intermyofibrillar mitochondrial density and smaller mitochondria. Collectively, these results suggest that alterations in muscle metabolism related to mitochondrial content and oxidative capacity may account for the reduced exercise capacity in Pus1(-/-) mice. PMID- 27197764 TI - Circadian rhythm of a red-tide dinoflagellate Peridinium quadridentatum in the port of Veracruz, Gulf of Mexico, its thecal morphology, nomenclature and geographical distribution. AB - A circadian rhythm of the dinoflagellate Peridinium quadridentatum was studied at a time-series station in the southwestern Gulf of Mexico, in May 2007. Different substrates (water column, the seagrass Thalassia testudinum, macroalgae, coral rubble and sandy sediment surface) were sampled at the site at 1.5-3.5m depth. In the samples of coral rubble, P. quadridentatum was scarce. In the water column, the species showed an abundance peak at 15:00. The cell abundance of P. quadridentatum in Thalassia samples increased from 15:00 until 18:00 (1.81*10(4)cells/gsubstratewet weight), and then continuously decreased until 06:00. Changes in P. quadridentatum cell abundance on macroalgae followed the same trend as on Thalassia, with the maximal value at 18:00. The higher abundance of P. quadridentatum (up to 1.40*10(4)cells/gSWW) in macroalgae samples showed the preference for seaweeds. P. quadridentatum has a neritic tropical-boreal distribution. A new combination is proposed: Peridinium quadridentatum var. trispiniferum. PMID- 27197765 TI - Assessment of heavy metal contamination in surface sediments of the west Guangdong coastal region, China. AB - Heavy metals (As, Cd, Cr, Cu, Hg, Pb, Zn), organic carbon and grain size of 237 surface sediment samples and one sediment core, taken from the west Guangdong coastal region in January 2008, were analyzed to evaluate the spatial distribution and pollution status. Results show that the ranges of the measured heavy metal concentrations in sediments are as follows: 8.33-39.49mg/kg for As, 0.1-1.49mg/kg for Cd, 33-108mg/kg for Cr, 11.5-78.8mg/kg for Cu, 0.04-0.26mg/kg for Hg, 21-73mg/kg for Pb, 56-248mg/kg for Zn. The heavy metal enrichment is closely associated with Corg and grain size. Both the metal enrichment factor and geoaccumulation index indicate that there was no detected pollution on metals As, Cr, Cu, Pb in our study area and a slight to moderate contamination of Cd, Hg and Zn. However, As, Cr and Cu have showed a certain risk. PMID- 27197766 TI - Absence of selenium protection against methylmercury toxicity in harbour seal leucocytes in vitro. AB - Previous studies described high concentrations of mercury (Hg) and selenium (Se) in the blood of harbour seals, Phoca vitulina from the North Sea. In the present study, we evaluated the in vitro potential protective effects of sodium selenite (Na2SeO3) and selenomethionine (SeMet) on cell proliferation of harbour seal lymphocytes exposed to MeHgCl 0.75MUM. In vitro exposure of ConA-stimulated T lymphocytes resulted in severe inhibition of DNA synthesis, likely linked to severe loss of mitochondrial membrane potential at 0.75MUM. Neither selenite nor SeMet showed a protective effect against MeHg toxicity expressed at the T lymphocyte proliferation level for harbour seals. Selenite and SeMet did not show negative effects regarding lymphocyte proliferation and mitochondrial membrane potential. To conclude, our results clearly demonstrated that MeHg affected in vitro immune cells exposure with no protective effects of selenium at a molar ratio Hg:Se of 1:10 in harbour seals from the North Sea. PMID- 27197767 TI - Novel bioluminescent coelenterazine derivatives with imidazopyrazinone C-6 extended substitution for Renilla luciferase. AB - Two series of novel coelenterazine analogues (alkynes and triazoles) with imidazopyrazinone C-6 extended substitution have been designed and synthesized successfully for the extension of bioluminescent substrates. After extensive evaluation, some compounds display excellent bioluminescence properties compared with DeepBlueC in cellulo, thus becoming potential molecules for bioluminescence techniques. PMID- 27197768 TI - From bench to bed and back again: phage therapy of childhood Escherichia coli diarrhea. AB - Over the last 20 years, the Nestle Research Center in Switzerland and the International Center for Diarrhoeal Diseases Research in Bangladesh have explored the efficacy of alternative biological agents for the treatment of diarrheal diseases. This paper reviews the work of this collaborative effort, particularly on Escherichia coli phage therapy (PT), and discusses the development of the project, starting with the isolation of T4-like coliphages from the stool of diarrhea patients, their pilot plant amplification and purification, and the constitution and testing of a cocktail of T4-like phages in mice. A series of phase I clinical trials has demonstrated the safety of PT. Oral phage given without protection survived gastric passage and was recovered in the feces. Oral T4 phage cocktail was then tested in parallel to a commercial phage product in a phase II randomized, placebo-controlled single-center trial in Bangladeshi children hospitalized with acute E. coli diarrhea. It was found that oral phage did not perform better than the current standard of care by oral rehydration/zinc treatment. Furthermore, fecal E. coli pathogen titers were low and mixed infections were found to be frequent. Microbiota analysis showed a correlation between diarrhea and increased levels of Streptococcus, which raises fundamental questions on the causative agent of diarrhea that may explain PT clinical failure. PMID- 27197770 TI - Major advantages and critical challenge for the proposed United States heart allocation system. AB - The proposed new United States allocation system incorporates extensive research into an elegant plan designed to reduce wait list mortality while preserving post transplant outcomes. All architects are to be congratulated. However, the future cannot be reliably modeled from the past as listing practices will evolve in response to new criteria. The new system should provide a major advance if and only if it is combined with a commitment to limit the number of listed patients overall and within each high priority status to the number that could reasonably undergo timely transplantation. PMID- 27197771 TI - The potential role of microRNAs in lung allograft rejection. AB - Lung transplantation (LT) has proven to be successful in carefully selected individuals with end-stage lung disease. However, long-term graft survival post LT is often hindered by the development of the bronchiolitis obliterans syndrome (BOS). Because BOS represents is a major problem for all LT centers, early identification and prediction of progressive loss of lung function is a major goal. MicroRNAs (miRNAs) play a major role in regulating many cellular functions, including epithelial-to-mesenchymal transition. miRNAs are emerging not only as biomarkers but also as potential therapy. The recognized importance of injured human bronchial epithelium in lung allograft dysfunction indicates that there is a need for research into the potential role of miRNAs. In this we review we summarize published findings in miRNAs implicated in lung and other types of allograft dysfunction and their role in maintaining the phenotype of epithelial cells after transplant injury. We also address potential clinical interventions that involve manipulating miRNA expression that may promote long-term airway integrity and graft survival. PMID- 27197769 TI - Effect of Exercise and Calorie Restriction on Tissue Acylcarnitines, Tissue Desaturase Indices, and Fat Accumulation in Diet-Induced Obese Rats. AB - Both exercise and calorie restriction interventions have been recommended for inducing weight-loss in obese states. However, there is conflicting evidence on their relative benefits for metabolic health and insulin sensitivity. This study seeks to evaluate the differential effects of the two interventions on fat mobilization, fat metabolism, and insulin sensitivity in diet-induced obese animal models. After 4 months of ad libitum high fat diet feeding, 35 male Fischer F344 rats were grouped (n = 7 per cohort) into sedentary control (CON), exercise once a day (EX1), exercise twice a day (EX2), 15% calorie restriction (CR1) and 30% calorie restriction (CR2) cohorts. Interventions were carried out over a 4-week period. We found elevated hepatic and muscle long chain acylcarnitines with both exercise and calorie restriction, and a positive association between hepatic long chain acylcarnitines and insulin sensitivity in the pooled cohort. Our result suggests that long chain acylcarnitines may not indicate incomplete fat oxidation in weight loss interventions. Calorie restriction was found to be more effective than exercise in reducing body weight. Exercise, on the other hand, was more effective in reducing adipose depots and muscle triglycerides, favorably altering muscle/liver desaturase activity and improving insulin sensitivity. PMID- 27197772 TI - The Zika epidemics and transplantation. AB - In the last few months an epidemic of Zika virus (ZIKV) has affected several countries, and it continues to spread rapidly. This virus was initially thought to cause only a mild febrile illness; however, the current epidemic has shown that it is associated with serious complications. Increasing reports are linking ZIKV to devastating conditions such as microcephaly in newborns and important neurologic syndromes. Although ZIKV infection has not yet been reported in transplant recipients, it is likely that it will be reported soon because of the number of transplants performed in affected areas and global travel. We discuss the effect of ZIKV in transplantation and propose recommendations to prevent donor-derived infections. PMID- 27197773 TI - Compassionate deactivation of ventricular assist devices in pediatric patients. AB - Despite greatly improved survival in pediatric patients with end-stage heart failure through the use of ventricular assist devices (VADs), heart failure ultimately remains a life-threatening disease with a significant symptom burden. With increased demand for donor organs, liberalizing the boundaries of case complexity, and the introduction of destination therapy in children, more children can be expected to die while on mechanical support. Despite this trend, guidelines on the ethical and pragmatic issues of compassionate deactivation of VAD support in children are strikingly absent. As VAD support for pediatric patients increases in frequency, the pediatric heart failure and palliative care communities must work toward establishing guidelines to clarify the complex issues surrounding compassionate deactivation. Patient, family and clinician attitudes must be ascertained and education regarding the psychological, legal and ethical issues should be provided. Furthermore, pediatric-specific planning documents for use before VAD implantation as well as deactivation checklists should be developed to assist with decision-making at critical points during the illness trajectory. Herein we review the relevant literature regarding compassionate deactivation with a specific focus on issues related to children. PMID- 27197774 TI - Balloon pulmonary angioplasty: A potential adjunct to pulmonary thromboendarterectomy. PMID- 27197775 TI - Adverse events in children implanted with ventricular assist devices in the United States: Data from the Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS). AB - BACKGROUND: Ventricular assist devices (VADs) have been used in children on an increasing basis in recent years. One-year survival rates are now >80% in multiple reports. In this report we describe adverse events experienced by children with durable ventricular assist devices, using a national-level registry (PediMACS, a component of INTERMACS) METHODS: PediMACS is a national registry that contains clinical data on patients who are <19 years of age at the time of VAD implantation. Data collection concludes at the time of VAD explantation. All FDA-approved devices are included. PediMACS was launched on September 1, 2012, and this report includes all data from launch until August 2014. Adverse events were coded with a uniform, pre-specified set of definitions. RESULTS: This report comprises data from 200 patients with a median age of 11 years (range 11 days to 18 years), and total follow-up of 783 patient-months. The diagnoses were cardiomyopathy (n = 146, 73%), myocarditis (n = 17, 9%), congenital heart disease (n = 35, 18%) and other (n = 2, 1%). Pulsatile-flow devices were used in 91 patients (45%) and continuous-flow devices in 109 patients (55%). Actuarial survival was 81% at 6 months. There were 418 adverse events reported. The most frequent events were device malfunction (n = 79), infection (n = 78), neurologic dysfunction (n = 52) and bleeding (n = 68). Together, these accounted for 277 events, 66% of the total. Although 38% of patients had no reported adverse event and 16% of patients had >=5 adverse events. Adverse events occurred at all time points after implantation, but were most likely to occur in the first 30 days. For continuous-flow devices, there were broad similarities in adverse event rates between this cohort and historic rates from the INTERMACS population. CONCLUSIONS: In this study cohort, the overall rate of early adverse events (within 90 days of implantation) was 86.3 events per 100 patient-months, and of late adverse events it was 20.4 events per 100 patient-months. The most common adverse events in recipients of pulsatile VADs were device malfunction, neurologic dysfunction, bleeding and infection. For continuous-flow VADs, the most common adverse events were infection, bleeding, cardiac arrhythmia, neurologic dysfunction and respiratory failure. Compared with an adult INTERMACS cohort, the overall rate and distribution of adverse events appears similar. PMID- 27197776 TI - Reply to the association between religion/spirituality and mental health in cancer. PMID- 27197777 TI - Positive influences of home food environment on primary-school children's diet and weight status: a structural equation model approach. AB - OBJECTIVES: The mechanism by which the home food environment (HFE) influences childhood obesity is unclear. The present study aimed to investigate the relationship between HFE and childhood obesity as mediated by diet in primary school children. DESIGN: Cross-sectional data collected from parents and primary school children participating in the Obesity Prevention and Lifestyle Evaluation Project. Only children aged 9-11 years participated in the study. Matched parent/child data (n 3323) were analysed. Exploratory factor analysis underlined components of twenty-one HFE items; these were linked to child diet (meeting guidelines for fruit, vegetable and non-core food intakes) and measured child BMI, in structural equation modelling, adjusting for confounders. SETTING: Twenty geographically bounded metropolitan and regional South Australian communities. SUBJECTS: School children and their parents from primary schools in selected communities. RESULTS: In the initial exploratory factor analysis, nineteen items remaining extracted eight factors with eigenvalues >1.0 (72.4 % of total variance). A five-factor structure incorporating ten items described HFE. After adjusting for age, gender, socio-economic status and physical activity all associations in the model were significant (P<0.05), explaining 9.3 % and 4.5 % of the variance in child diet and BMI, respectively. A more positive HFE was directly and indirectly associated with a lower BMI in children through child diet. CONCLUSIONS: The robust statistical methodology used in the present study provides support for a model of direct and indirect dynamics between the HFE and childhood obesity. The model can be tested in future longitudinal and intervention studies to identify the most effective components of the HFE to target in childhood obesity prevention efforts. PMID- 27197778 TI - Limits of agricultural greenhouse gas calculators to predict soil N2O and CH4 fluxes in tropical agriculture. AB - Demand for tools to rapidly assess greenhouse gas impacts from policy and technological change in the agricultural sector has catalyzed the development of 'GHG calculators'- simple accounting approaches that use a mix of emission factors and empirical models to calculate GHG emissions with minimal input data. GHG calculators, however, rely on models calibrated from measurements conducted overwhelmingly under temperate, developed country conditions. Here we show that GHG calculators may poorly estimate emissions in tropical developing countries by comparing calculator predictions against measurements from Africa, Asia, and Latin America. Estimates based on GHG calculators were greater than measurements in 70% of the cases, exceeding twice the measured flux nearly half the time. For 41% of the comparisons, calculators incorrectly predicted whether emissions would increase or decrease with a change in management. These results raise concerns about applying GHG calculators to tropical farming systems and emphasize the need to broaden the scope of the underlying data. PMID- 27197781 TI - Optimal management of severe trauma in France: How close are we? PMID- 27197782 TI - Erratum to "Correlation between the radiation responses of fibroblasts cultured from individual patients and the risk of late reaction after breast radiotherapy" [Cancer Lett. 374/2 (2016) 324-330]. PMID- 27197779 TI - A resistance locus in the American heirloom rice variety Carolina Gold Select is triggered by TAL effectors with diverse predicted targets and is effective against African strains of Xanthomonas oryzae pv. oryzicola. AB - The rice pathogens Xanthomonas oryzae pathovar (pv.) oryzae and pv. oryzicola produce numerous transcription activator-like (TAL) effectors that increase bacterial virulence by activating expression of host susceptibility genes. Rice resistance mechanisms against TAL effectors include polymorphisms that prevent effector binding to susceptibility gene promoters, or that allow effector activation of resistance genes. This study identifies, in the heirloom variety Carolina Gold Select, a third mechanism of rice resistance involving TAL effectors. This resistance manifests through strong suppression of disease development in response to diverse TAL effectors from both X. oryzae pathovars. The resistance can be triggered by an effector with only 3.5 central repeats, is independent of the composition of the repeat variable di-residues that determine TAL effector binding specificity, and is independent of the transcriptional activation domain. We determined that the resistance is conferred by a single dominant locus, designated Xo1, that maps to a 1.09 Mbp fragment on chromosome 4. The Xo1 interval also confers complete resistance to the strains in the African clade of X. oryzae pv. oryzicola, representing the first dominant resistance locus against bacterial leaf streak in rice. The strong phenotypic similarity between the TAL effector-triggered resistance conferred by Xo1 and that conferred by the tomato resistance gene Bs4 suggests that monocots and dicots share an ancient or convergently evolved mechanism to recognize analogous TAL effector epitopes. PMID- 27197783 TI - Acculturation levels and personalizing orthognathic surgery for the Asian American patient. AB - This study was performed to investigate whether the level of acculturation among Asians living in the USA plays a significant role in their opinion of facial profiles. One hundred and ninety-eight Asian American subjects were asked to complete a pre-validated survey to measure their level of acculturation and to evaluate four sets of pictures that displayed a class II male, class II female, class III male, and class III female. Each set consisted of three lateral profile pictures: an initial unaltered photo, a picture simulating a flatter profile (orthodontic camouflage in class II; mandibular setback in class III), and a picture simulating a fuller profile (mandibular advancement in class II; maxillary advancement in class III). For the class II male, subjects who were more acculturated indicated that a flatter profile (orthodontic camouflage) was less attractive. For the class II female, higher acculturated subjects chose expansive treatment (mandibular advancement) as more aesthetic compared to the less acculturated subjects. Each of these scenarios had statistically significant odds ratios. In general, highly acculturated subjects preferred a fuller facial profile, while low acculturated subjects preferred a flatter facial profile appearance, except for the class III female profile, which did not follow this trend. PMID- 27197780 TI - A specific plasminogen activator inhibitor-1 antagonist derived from inactivated urokinase. AB - Fibrinolysis is a process responsible for the dissolution of formed thrombi to re establish blood flow after thrombus formation. Plasminogen activator inhibitor-1 (PAI-1) inhibits urokinase-type and tissue-type plasminogen activator (uPA and tPA) and is the major negative regulator of fibrinolysis. Inhibition of PAI-1 activity prevents thrombosis and accelerates fibrinolysis. However, a specific antagonist of PAI-1 is currently unavailable for therapeutic use. We screened a panel of uPA variants with mutations at and near the active site to maximize their binding to PAI-1 and identified a potent PAI-1 antagonist, PAItrap. PAItrap is the serine protease domain of urokinase containing active-site mutation (S195A) and four additional mutations (G37bR-R217L-C122A-N145Q). PAItrap inhibits human recombinant PAI-1 with high potency (Kd = 0.15 nM) and high specificity. In vitro using human plasma, PAItrap showed significant thrombolytic activity by inhibiting endogenous PAI-1. In addition, PAItrap inhibits both human and murine PAI-1, allowing the evaluation in murine models. In vivo, using a laser-induced thrombosis mouse model in which thrombus formation and fibrinolysis are monitored by intravital microscopy, PAItrap reduced fibrin generation and inhibited platelet accumulation following vascular injury. Therefore, this work demonstrates the feasibility to generate PAI-1 inhibitors using inactivated urokinase. PMID- 27197784 TI - Correlation of gender and age with magnetic resonance imaging findings in patients with arthrogenic temporomandibular disorders: a cross-sectional study. AB - The objective of this study was to analyse the correlation between the gender and age of individuals with arthrogenic temporomandibular disorders (TMDs) and magnetic resonance imaging (MRI) findings. A total of 199 patients were included in the study and were divided into four age groups: group A, <=30 years; group B, 31-44 years; group C, 45-55 years; group D, >=56 years. MRI scans were analysed for the presence or absence of the following conditions: morphological changes in the mandibular condyle and/or articular tubercle, disc displacement with (DDWR) and without reduction (DDWoR), bone oedema, effusion, and avascular necrosis. Statistical analyses were conducted using logistic regression models (P<0.05). The mean patient age was 44.47+/-16.39 years; 158 (79.4%) were female and 41 (20.6%) were male. Only DDWoR was more significantly found in females than in males (P<0.05). Group D showed an odds ratio three times higher for the presence of morphological changes than group A (odds ratio 3.042, 95% confidence interval 1.421-6.512; P=0.0042). No differences were found among groups for the other findings. Based on the results of the present study it may be concluded that MRI findings tend to differ according to age and gender. PMID- 27197785 TI - [Mucinous nevus of late onset]. AB - INTRODUCTION: Mucinous nevus is a rare disease characterized by mucin deposits in the dermis, with only 23 cases reported to date. It belongs to the connective tissue nevus family and is characterized by dermal mucin deposits. Two histological subtypes have been described: pure mucinous dermal nevus (connective tissue nevus of the proteoglycan [CTNP]) and combined mucinous nevus (combined CTNP) associating epidermal nevus with dermal mucin deposits. Lesions generally appear in childhood or early adulthood. We report herein the case of a 59-year old man with a symptomatic lesion. OBSERVATION: A 59-year-old man consulted for unilateral lesions occurring linearly along the Blaschko line on the right lower limb, composed of brown verrucous papules, which started at the age of 50. The patient complained of itching caused by friction from clothes. Histological examination of a papule highlighted an acanthotic epidermis, with elongation of rete ridges and mucin deposits in the dermis showing uptake of alcian blue stain. The clinicopathological analysis enabled diagnosis of combined CTNP. We treated this nevus by surgical dermabrasion and observed a slight and cosmetically acceptable scar. DISCUSSION: To our knowledge, our patient is the oldest reported to date and the only one to have complained of symptoms. Our review of the literature highlights the importance of skin biopsy to guide aesthetic or symptomatic treatment. CO2 laser and dermabrasion are recommended for combined CTNP as they treat the epidermal component with low risk of secondary scarring. However, these techniques should be avoided in pure dermal CTNP, where surgical excision alone is acceptable in order to achieve optimal cosmetic results. PMID- 27197786 TI - Association Between Headaches and Tinnitus in Young Adults: Cross-Sectional Study. AB - OBJECTIVE: To study the association between migraine and tinnitus in a large, cross-sectional study among students. BACKGROUND: Tinnitus has been associated with various pain syndromes, including headaches. However, prior studies were mainly conducted among elderly adults. METHODS: Cross-sectional study among 5729 participants of the French internet-based Students Health Research Enterprise (i Share) cohort. Health, personal and lifestyle habits, and socio-demographics characteristics as well as headache/migraine symptoms and tinnitus, were recorded in a standardized questionnaire based on self-reports. Logistic regression models were used to evaluate the association between the students' headache status and tinnitus. RESULTS: The 5729 participants had a mean age of 20.8 years (standard deviation 2.8 years), 75.4% were female, and 1645 reported migraine. An association was found between the students' headache status and tinnitus after adjustment for confounding variables. Tinnitus was reported by 8.9% of participants with migraine, 7.3% of patients with migraine without aura, and 10.8% of participants with migraine with aura. The adjusted odds ratios of tinnitus were 1.77 (95% confidence interval, 1.36-2.30) for migraine and 1.38 (0.98-1.92) for non-migraine headache. The association was stronger for students with migraine with aura (odds ratio = 2.10, 95% confidence interval 1.54-2.86) than for migraine without aura (odds ratio = 1.51, 95% confidence interval 1.09 2.07). CONCLUSION: We found an association between migraine and tinnitus among young individuals, which was strongest for the subgroup migraine with aura. PMID- 27197787 TI - Time trend in incidence of malignant neoplasms of the central nervous system in relation to mobile phone use among young people in Japan. AB - The aim of this study was to examine whether incidence of malignant neoplasms of the central nervous system from 1993 to 2010 has increased among young people in Japan, and whether the increase could be explained by increase in mobile phone use. Joinpoint regression analysis of incidence data was performed. Subsequently, the expected incidence rate was calculated assuming that the relative risk was 1.4 for those who used mobile phones more than 1640 h cumulatively. Annual percent change was 3.9% (95% confidence interval [CI], 1.6-6.3) for men in their 20s from 1993 to 2010, 12.3% (95% CI, 3.3-22.1) for women in their 20s from 2002 to 2010, 2.7% (95% CI, 1.3-4.1) for men in their 30s from 1993 to 2010, and 3.0% (95% CI, 1.4-4.7) for women in their 30s from 1993 to 2010. Change in incidence rates from 1993 to 2010 was 0.92 per 100,000 people for men in their 20s, 0.83 for women in their 20s, 0.89 for men in their 30s, and 0.74 for women in their 30s. Change in expected incidence rates from 1993 to 2010 was 0.08 per 100,000 people for men in their 20s, 0.03 for women in their 20s, 0.15 for men in their 30s, and 0.05 for women in their 30s. Patterns in sex-, age-, and period-specific incidence increases are inconsistent with sex-, age-, and period-specific prevalence trends, suggesting the overall incidence increase cannot be explained by heavy mobile phone use. Bioelectromagnetics. 37:282-289, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27197788 TI - The log TSH-free T4 relationship in a community-based cohort is nonlinear and is influenced by age, smoking and thyroid peroxidase antibody status. AB - BACKGROUND: The TSH-T4 relationship was thought to be inverse log-linear, but recent cross-sectional studies of selected populations report a complex, nonlinear relationship. The TSH-T4 relationship has not been evaluated in an unselected, community-based cohort, and there are limited data regarding clinical factors which affect it. OBJECTIVE: To analyse the TSH-free T4 relationship in a community-based cohort. DESIGN, PARTICIPANTS AND METHODS: In a cross-sectional, retrospective study, we analysed serum TSH and free T4 concentrations from 4427 participants (55% female) in the 1994 Busselton Health Study who were not taking thyroxine. Simple linear, segmented-linear and nonlinear regression models of log10 TSH on free T4 were compared for goodness of fit. RESULTS: All 5 log TSH free T4 models tested (separate lines, segmented conterminal line, quartic, error function, double-sigmoid curve) fitted significantly better than a simple linear model (each P < 0.01 by Vuong test). Ranking by Akaike information criterion indicated that the segmented conterminal line and double-sigmoid models provided best fit, followed by the error function, quartic and separate lines models. From multiple regression analysis, age tertile, current smoking and TPOAb status each significantly influenced the TSH-free T4 relationship, whereas BMI category and diabetes did not. A sex difference in the TSH-free T4 relationship was apparent only in the lower part of the free T4 reference range. CONCLUSION: In a community based setting, the relationship between log TSH and free T4 is complex, nonlinear and influenced by age, smoking and TPOAb status. PMID- 27197789 TI - Enzymatic lipophilization of epicatechin with free fatty acids and its effect on antioxidative capacity in crude camellia seed oil. AB - BACKGROUND: Crude camellia seed oil is rich in free fatty acids, which must be removed to produce an oil of acceptable quality. In the present study, we reduced the free fatty acid content of crude camellia seed oil by lipophilization of epicatechin with these free fatty acids in the presence of Candida antarctica lipase B (Novozym 435), and this may enhance the oxidative stability of the oil at the same time. RESULTS: The acid value of crude camellia seed oil reduced from 3.7 to 2.5 mgKOH g-1 after lipophilization. Gas chomatography-mass spectrometry analysis revealed that epicatechin oleate and epicatechin palmitate were synthesized in the lipophilized oil. The peroxide, p-anisidine, and total oxidation values during heating of the lipophilized oil were much lower than that of the crude oil and commercially available camellia seed oil, suggesting that lipophilized epicatechin derivatives could help enhance the oxidative stability of edible oil. CONCLUSION: The enzymatic process to lipophilize epicatechin with the free fatty acids in crude camellia seed oil described in the present study could decrease the acid value to meet the quality standards for commercial camellia seed oil and, at the same time, obtain a new edible camellia seed oil product with good oxidative stability. (c) 2016 Society of Chemical Industry. PMID- 27197790 TI - Apo J and Apo D: Complementary or Antagonistic Roles in Alzheimer's Disease? AB - Apolipoprotein D (Apo D) and Apolipoprotein J (Apo J) are among the only nine apolipoproteins synthesized in the nervous system. Apart from development, these apolipoproteins are implicated in the normal aging process as well as in different neuropathologies as Alzheimer's disease (AD), where a neuroprotective role has been postulated. Different authors have proposed that Apo D and Apo J could be biomarkers for AD but as far as we know, there are no studies about the relationship between them as well as their expression pattern along the progression of the disease. In this paper, using double immunohistochemistry techniques, we have demonstrated that Apo D is mainly located in glial cells while Apo J expression preferentially occurs in neurons; both proteins are also present in AD diffuse and mature senile plaques but without signal overlap. In addition, we have observed that Apo J and Apo D immunostaining shows a positive correlation with the progression of the disease and the Braak's stages. These results suggest complementary and cell-dependent neuroprotective roles for each apolipoprotein during AD progress. PMID- 27197791 TI - Deceit and dishonesty as practice: the comfort of lying. AB - Lying and deceit are instruments of power, used by social actors in the pursuit of their practices as they seek to maintain social order. All social actors, nurses included, have deceit and dishonesty within their repertoire of practice. Much of this is benign, well intentioned and a function of being sociable and necessary in the pursuit of social order in the healthcare environment. Lying and deceit from a sociological point of view, is a reflection of the different modes of domination that exist within a social space. French philosopher Pierre Bourdieu theorized about the way that symbolic power works within social space. The social structures and the agency of individual actors moving within it are interrelated and interdependent. Bourdieu's ideas will be used to theorize about real clinical experiences where acts of deceit can be identified and a case example will be presented. Nurses are actors in the social space of clinical care, and their world is complex, challenging, and often fraught with the contradictory demands and choices that reflect and influence their behaviours. An exploration of lying and deceit in nursing as an instrument in the modes of domination that persist enables us to challenge some of the assumptions that are made about the motives that cause or tempt nurses to lie as well as to understand the way on which they are sometimes lied to, according to the acts of domination that exist in the field. Lying or acting dishonestly is a powerful act that is intent on retaining stability and social order and could be seen to be a justification of lying and deceit. However, we need to pause and consider, in whose interests are we striving to create social order? Is it in the end about the comfort of patients or for the comfort of professionals? PMID- 27197792 TI - Genetic antimicrobial susceptibility testing in Gram-negative sepsis - impact on time to results in a routine laboratory. AB - Diagnostic testing of positive blood cultures is among the most critical tasks performed by clinical microbiology laboratories, and the total analysis time from sampling to results should be kept as short as possible. By providing identification of pelleted bacteria directly from positive blood-cultures, MALDI TOF MS opens for relatively low-complex species-adjusted genetic susceptibility testing from the same bacterial pellet. In our lab routine, we prospectively evaluated a rapid in-house real-time PCR targeting the most common aminoglycoside and cephalosporin resistance genes in Escherichia coli and Klebsiella pneumoniae and measured time to preliminary susceptibility reporting for 138 samples. The results were compared to direct phenotypic susceptibility testing with interpretation after 6 h and overnight incubation respectively. Results from the genetic susceptibility testing were available for 69.5% (96/138) of the positive blood cultures within 24 h after sample collection. No phenotypic susceptibility results were available at this time. Compared to overnight direct susceptibility testing, the average time from sample collection to preliminary susceptibility reporting was reduced with 43%, from 45 h and 5 min to 25 h and 44 min, providing an earlier adjustment of antimicrobial therapy for 12 patients. Minor logistic adjustments have the potential to save yet another 4 h. PMID- 27197793 TI - The DNA damage response molecule MCPH1 in brain development and beyond. AB - Microcephalin (MCPH1) is identified as being responsible for the neurodevelopmental disorder primary microcephaly type 1, which is characterized by a smaller-than-normal brain size and mental retardation. MCPH1 has originally been identified as an important regulator of telomere integrity and of cell cycle control. Genetic and cellular studies show that MCPH1 controls neurogenesis by coordinating the cell cycle and the centrosome cycle and thereby regulating the division mode of neuroprogenitors to prevent the exhaustion of the progenitor pool and thereby microcephaly. In addition to its role in neurogenesis, MCPH1 plays a role in gonad development. MCPH1 also functions as a tumor suppressor in several human cancers as well as in mouse models. Here, we review the role of MCPH1 in DNA damage response, cell cycle control, chromosome condensation and chromatin remodeling. We also summarize the studies on the biological functions of MCPH1 in brain size determination and in pathologies, including infertility and cancer. PMID- 27197795 TI - HIV Vaccine Awareness Day: sustaining the momentum. PMID- 27197794 TI - Naps promote flexible memory retrieval in 12-month-old infants. AB - Flexibility in applying existing knowledge to similar cues is a corner stone of memory development in infants. Here, we examine the effect of sleep on the flexibility of memory retrieval using a deferred imitation paradigm. Forty-eight 12-month-old infants were randomly assigned to either a nap or a no-nap demonstration condition (scheduled around their natural daytime sleep schedule) or to a baseline control condition. In the demonstration conditions, infants watched an experimenter perform three target actions on a hand puppet. Immediately afterwards, infants were allowed to practice the target actions three times. In a test session 4-hr later, infants were given the opportunity to reproduce the actions with a novel hand puppet differing in color from the puppet used during the demonstration session. Only infants in the nap-condition performed significantly more target actions than infants in the baseline control condition. Furthermore, they were faster to carry out the first target action than infants in the no-nap condition. We conclude that sleep had a facilitative effect on infants' flexibility of memory retrieval. PMID- 27197796 TI - Pregnancy in the liver transplant recipient. AB - During gestation, the woman's body undergoes various changes, and the line between physiology and pathology is very thin even in healthy women. Today, many of the liver transplant recipients are young women, who at one point in their lives may consider the possibility of pregnancy. Clinicians have to counsel them about the time of conception, the risk of miscarriage, the deterioration of the mother's health status, and the risk of birth defects. This review, based on our 20 years of clinical experience and up-to-date literature, provides comprehensive guidelines on pregnancy management in liver transplant recipients. Pregnancy in liver transplant recipients is possible but never physiological. Proper management and pharmacotherapy lowers the incidence of complications and birth defects. Critical factors for perinatal success include stable graft function before pregnancy, proper preparation for pregnancy, and cautious observation during its course. Liver Transplantation 22 1408-1417 2016 AASLD. PMID- 27197798 TI - 3D Printing in the Laboratory: Maximize Time and Funds with Customized and Open Source Labware. AB - 3D printing, also known as additive manufacturing, is the computer-guided process of fabricating physical objects by depositing successive layers of material. It has transformed manufacturing across virtually every industry, bringing about incredible advances in research and medicine. The rapidly growing consumer market now includes convenient and affordable "desktop" 3D printers. These are being used in the laboratory to create custom 3D-printed equipment, and a growing community of designers are contributing open-source, cost-effective innovations that can be used by both professionals and enthusiasts. User stories from investigators at the National Institutes of Health and the biomedical research community demonstrate the power of 3D printing to save valuable time and funding. While adoption of 3D printing has been slow in the biosciences to date, the potential is vast. The market predicts that within several years, 3D printers could be commonplace within the home; with so many practical uses for 3D printing, we anticipate that the technology will also play an increasingly important role in the laboratory. PMID- 27197797 TI - Comprehensive clinical assessment of home-based older persons within New Zealand: an epidemiological profile of a national cross-section. AB - OBJECTIVE: Since 2012, all community care recipients in New Zealand have undergone a standardised needs assessment using the Home Care International Residential Assessment Instrument (interRAI-HC). This study describes the national interRAI-HC population, assesses its data quality and evaluates its ability to be matched. METHODS: The interRAI-HC instrument elicits information on 236 questions over 20 domains; conducted by 1,800+ trained health professionals. Assessments between 1 July 2012 and 30 June 2014 are reported here. Stratified by age, demographic characteristics were compared to 2013 Census estimates and selected health profiles described. Deterministic matching to the Ministry of Health's mortality database was undertaken. RESULTS: Overall, 51,232 interRAI-HC assessments were conducted, with 47,714 (93.1%) research consent from 47,236 unique individuals; including 2,675 Maori and 1,609 Pacific people. Apart from height and weight, data validity and reliability were high. A 99.8% match to mortality data was achieved. CONCLUSIONS: The interRAI-HC research database is large and ethnically diverse, with high consent rates. Its generally good psychometric properties and ability to be matched enhances its research utility. IMPLICATIONS: This national database provides a remarkable opportunity for researchers to better understand older persons' health and health care, so as to better sustain older people in their own homes. PMID- 27197799 TI - Metal Ions and Metal Complexes in Alzheimer's Disease. AB - BACKGROUND: Alzheimer's disease (AD) is the most common form of dementia that seriously affects daily life. Even if AD pathogenesis is still subject of debate, it is generally accepted that cerebral cortex plaques formed by aggregated amyloid-beta (Abeta) peptides can be considered a characteristic pathological hallmark. It is well known that metal ions play an important role in the aggregation process of Abeta. METHODS: This review focuses on the anti-Abeta aggregation activity of chelating ligands as well as on the use of metal complexes as diagnostic probes and as potential drugs. CONCLUSION: While chelating agents, such as curcumin or flavonoid derivatives, are currently used to capture metal ions responsible for Abeta aggregation, the potential application of platinum, ruthenium and cobalt complexes, among others, of several heterocyclic ligands, represents a promising new strategy to fight AD. PMID- 27197800 TI - Functional Characterization of PyrG, an Unusual Nonribosomal Peptide Synthetase Module from the Pyridomycin Biosynthetic Pathway. AB - Pyridomycin is an antimycobacterial cyclodepsipeptide assembled by a nonribosomal peptide synthetase/polyketide synthase hybrid system. Analysis of its cluster revealed a nonribosomal peptide synthetase (NRPS) module, PyrG, that contains two tandem adenylation domains and a PKS-type ketoreductase domain. In this study, we biochemically validated that the second A domain recognizes and activates alpha keto-beta-methylvaleric acid (2-KVC) as the native substrate; the first A domain was not functional but might play a structural role. The KR domain catalyzed the reduction of the 2-KVC tethered to the peptidyl carrier protein of PyrG in the presence of the MbtH family protein, PyrH. PyrG was demonstrated to recognize many amino acids. This substrate promiscuity provides the potential to generate pyridomycin analogues with various enolic acids moiety; this is important for binding InhA, a critical enzyme for cell-wall biosynthesis in Mycobacterium tuberculosis. PMID- 27197801 TI - Efficacy, safety and pharmacokinetics of a new high-purity factor X concentrate in subjects with hereditary factor X deficiency. AB - INTRODUCTION: Hereditary factor X (FX) deficiency is a rare bleeding disorder affecting 1:500 000 to 1:1 000 000 of individuals. Until recently, no specific replacement factor concentrate was available. AIM: The aim of this study was to assess safety and efficacy of a new, high-purity plasma-derived FX concentrate (pdFX) in subjects with hereditary FX deficiency. METHODS: Subjects aged >=12 years with moderate or severe FX deficiency (plasma FX activity <5 IU dL(-1) ) received 25 IU kg(-1) pdFX as on-demand treatment or short-term prophylaxis for 6 months to 2 years. Subjects assessed pdFX efficacy for each bleed; at end-of study, investigators assessed overall pdFX efficacy. Blood samples for pharmacokinetic analysis were obtained at baseline and >=6 months. Safety was assessed by adverse events (AEs), inhibitor development and changes in laboratory parameters. RESULTS: Sixteen enrolled subjects (six aged 12-17 years; 10 aged 18 58 years) received a total of 468 pdFX infusions. In the 187 analysed bleeds, pdFX efficacy was categorized as excellent, good, poor or unassessable in 90.9%, 7.5%, 1.1% and 0.5% of bleeds respectively; 83% of bleeds were treated with one infusion. For pdFX, mean (median; interquartile range) incremental recovery and half-life were 2.00 (2.12; 1.79-2.37) IU dL(-1) per IU kg(-1) and 29.4 (28.6; 25.8-33.1) h respectively. No serious AEs possibly related to pdFX or evidence of FX inhibitors were observed, and no hypersensitivity reactions or clinically significant trends were detected in laboratory parameters. CONCLUSION: These results demonstrate that a dose of 25 IU kg(-1) pdFX is safe and efficacious for on-demand treatment and short-term prophylaxis in subjects with moderate or severe hereditary FX deficiency. PMID- 27197803 TI - Assessing women's knowledge and attitudes toward cord blood banking: policy and ethical implications for Jordan. AB - BACKGROUND: Despite the global expansion of umbilical cord blood (CB) banking, little is known about public opinion and awareness, especially among Arab Muslim populations. CB banking raises policy questions about funding sustainability and quality standards, as well as ethical debates about profitability, informed consent, and medical justification. This study is the first of its kind in the Arab world, and Jordan has a unique, understudied, yet highly relevant setting, especially as a regional medical hub with advanced medical and health policy infrastructures. In addition, the first private and public CB banks are expected to open in 2016. STUDY DESIGN AND METHODS: The authors developed and administered, over a 5-month period, an anonymous survey to investigate public opinion and knowledge about CB banking in Jordan. The survey was administered to women in maternity outpatient clinic waiting rooms at five different hospitals. RESULTS: More than 75% of respondents indicated they knew nothing about CB banking in Jordan, and more than 50% had never heard of CB banking before. However, overall public opinion about CB storage is positive. Important factors related to public opinion were also identified, demonstrating that most women want more information on CB banking, especially from their obstetrician. CONCLUSION: This widespread lack of awareness is likely contributing to misinformation, lack of knowledge, and unfavorable perspectives toward CB donation and research. The results have important implications for the development of national and regional policies and educational campaigns on CB banking targeting both physicians and patients. PMID- 27197804 TI - Electrophysiologic Scar Substrate in Relation to VT: Noninvasive High-Resolution Mapping and Risk Assessment with ECGI. AB - BACKGROUND: Ischemic cardiomyopathy (ICM) can provide the substrate for ventricular tachycardia (VT). OBJECTIVE: To map noninvasively with high resolution the electrophysiologic (EP) scar substrate, identify its relationship to reentry circuits during VT, and stratify VT risk in ICM patients. METHODS: Noninvasive high-resolution epicardial mapping with electrocardiographic imaging (ECGI) was performed in 32 ICM patients (17 with clinical VT, 15 without VT). Abnormal scar EP substrate was determined based on electrogram (EGM) amplitude (as percentage of maximal peak-to-peak voltage over the entire ventricular epicardium; total scar [TS] < 30%; dense scar [DS] < 15%), fractionation, and presence of late potentials (LPs). Scar burden was defined as the ratio of the scar size to the total epicardial surface area. The VT activation pattern was mapped and correlated with the EP substrate to identify components of the reentry circuit. RESULTS: Patients with VT had higher scar burden (TS: 51.0 +/- 9.3% vs 36.5 +/- 5.4%, P < 0.05; DS: 29.5 +/- 7.3% vs 16.8 +/- 6.8%, P < 0.05) with lower normalized unipolar EGM voltage (TS: 0.107 +/- 0.027 vs 0.153 +/- 0.031, P < 0.05; DS: 0.073 +/- 0.023 vs 0.098 +/- 0.026, P < 0.05), greater prevalence of fractionated EGMs (TS: 44.1 +/- 10.6% vs 26.8 +/- 6.3%, P < 0.05; DS: 50.8 +/- 10.8% vs 30.9 +/- 7.0%, P < 0.05), and LPs (TS: 26.8 +/- 10.7% vs 15.8 +/- 5.3, P < 0.05). VTs were mapped in eight patients; the reentry circuits were closely related to the EP substrate. CONCLUSIONS: ECGI noninvasively identified scar EP substrate that underlies abnormal conduction in ICM patients. It identified regions within the scar that aligned with critical elements of the reentry circuit during VT. ECGI can potentially be used for VT risk stratification in ICM patients. PMID- 27197805 TI - Prevalence and risk factors of advanced colorectal neoplasms in asymptomatic Korean people between 40 and 49 years of age. AB - BACKGROUND AND AIM: Current guidelines recommend colon cancer screening for persons aged over 50 years. However, there are few data on colorectal cancer screening in 40- to 49-year-olds. This study assessed the prevalence and risk factors of colorectal neoplasms in 40- to 49-year-old Koreans. METHODS: We analyzed the results of screening colonoscopies of 6680 persons 40-59 years of age (2206 aged 40-49 and 4474 aged 50-59 years). RESULTS: The prevalence of overall and advanced neoplasms in the 40- to 49-year age group was lower than in the 50- to 59-year age group (26.7% and 2.4% vs 37.8% and 3.5%, respectively). However, the prevalence of overall and advanced neoplasms increased to 39.1% and 5.4%, respectively, in 45- to 49-year-old individuals with metabolic syndrome. In the 40- to 49-year age group, age, current smoking, and metabolic syndrome were associated with an increased risk of advanced neoplasms (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.04-1.30; OR 3.12, 95% CI 1.20-8.12; and OR 2.00, 95% CI 1.09-3.67, respectively). CONCLUSIONS: Individuals aged 40-49 years had a lower prevalence of colorectal neoplasms than those aged 50-59 years, but some 40 to 49-year-olds showed a similar prevalence to those aged 50-59 years. Age, current smoking habits, and metabolic syndrome are associated with an increased risk of advanced neoplasms in subjects aged 40-49 years. Further studies are needed to stratify the risks of colon cancer and guide targeted screening in persons younger than 50 years old. PMID- 27197807 TI - Nanoscale Electrodes for Flexible Electronics by Swelling Controlled Cracking. AB - Nanogap electrodes are realized using pre-patterned electrodes and a swelling controlled cracking method. Parallel fabrication of nanogap electrodes on flexible substrates can be achieved using this method. This swelling-controlled cracking method is promising for fabricating high-performance flexible electronics. UV photodetectors with ZnO nanoparticle-bridged nanogap electrodes exhibit high responsivity and external quantum efficiency. PMID- 27197806 TI - Quantification of liver proton-density fat fraction in 7.1T preclinical MR systems: Impact of the fitting technique. AB - PURPOSE: To investigate the feasibility of estimating the proton-density fat fraction (PDFF) using a 7.1T magnetic resonance imaging (MRI) system and to compare the accuracy of liver fat quantification using different fitting approaches. MATERIALS AND METHODS: Fourteen leptin-deficient ob/ob mice and eight intact controls were examined in a 7.1T animal scanner using a 3D six-echo chemical shift-encoded pulse sequence. Confounder-corrected PDFF was calculated using magnitude (magnitude data alone) and combined fitting (complex and magnitude data). Differences between fitting techniques were compared using Bland Altman analysis. In addition, PDFFs derived with both reconstructions were correlated with histopathological fat content and triglyceride mass fraction using linear regression analysis. RESULTS: The PDFFs determined with the use of both reconstructions correlated very strongly (r = 0.91). However, small mean bias between reconstructions demonstrated divergent results (3.9%; confidence interval [CI] 2.7-5.1%). For both reconstructions, there was linear correlation with histopathology (combined fitting: r = 0.61; magnitude fitting: r = 0.64) and triglyceride content (combined fitting: r = 0.79; magnitude fitting: r = 0.70). CONCLUSION: Liver fat quantification using the PDFF derived from MRI performed at 7.1T is feasible. PDFF has strong correlations with histopathologically determined fat and with triglyceride content. However, small differences between PDFF reconstruction techniques may impair the robustness and reliability of the biomarker at 7.1T. J. Magn. Reson. Imaging 2016;44:1425-1431. PMID- 27197809 TI - Analysis of pesticide residues in tobacco with online size exclusion chromatography with gas chromatography and tandem mass spectrometry. AB - An ultrasensitive method for the simultaneous analysis of pesticides residues in tobacco was developed with online size exclusion chromatography with gas chromatography and tandem mass spectrometry. Tobacco samples were extracted with the solvent mixture of cyclohexane and acetone (7:3, v/v) and centrifuged. Then, the supernatant liquors were injected directly into the online size exclusion chromatography with gas chromatography and tandem mass spectrometry without any other purification procedures after being filtered with a 0.22 MUm organic phase filter. The matrix interferences were effectively removed and recoveries of most pesticides were in the range of 72-121%. Especially, for chlorothalonil, the analysis efficiency of this method was much more favorable than that of the general method, in which dispersive solid-phase extraction was used as an additional purified procedure. In addition, the limits of quantitation of this method were from 1 to 50 MUg/kg. Therefore, a rapid, cost-effective, labor-saving method was proposed in the present work, which was suitable for the analysis of 41 pesticide residues in tobacco. PMID- 27197808 TI - Crizotinib primary resistance overcome by ceritinib in a patient with ALK rearranged non-small cell lung cancer. AB - We report on the case of a patient affected by advanced non-small cell lung cancer (NSCLC) harboring an anaplastic lymphoma kinase (ALK) gene rearrangement who did not respond to crizotinib but subsequently benefited from treatment with ceritinib (LDK378). Although second-generation ALK inhibitors have shown activity in patients pretreated with crizotinib who experienced secondary resistance, this is the first report to date describing their efficacy in a case of primary resistance. Of note, none of the previously described molecular mechanisms explaining resistance to crizotinib was detected on either the initial or post crizotinib biopsies. We hypothesize that crizotinib was powerless in controlling disease progression due to its inadequate inhibition of ALK signaling. Although we lack any molecular evidence elucidating the primary crizotinib resistance, we believe that ceritinib treatment led to tumor regression thanks to its superior biological potency. PMID- 27197810 TI - NMR spectroscopy of filtered serum of prostate cancer: A new frontier in metabolomics. AB - BACKGROUND: To address the shortcomings of digital rectal examinations (DRE), serum prostate-specific antigen (PSA), and trans-rectal ultrasound (TRUS) for precise determination of prostate cancer (PC) and differentiation from benign prostatic hyperplasia (BPH), we applied (1) H-nuclear magnetic resonance (NMR) spectroscopy as a surrogate tactic for probing and prediction of PC and BPH. METHODS: The study comprises 210 filtered sera from suspected PC, BPH, and a healthy subjects' cohort (HC). The filtered serum approach delineates to identify and quantify 52 metabolites using (1) H NMR spectroscopy. All subjects had undergone clinical evaluations (DRE, PSA, and TRUS) followed by biopsy for Gleason score, if needed. NMR-measured metabolites and clinical evaluation data were examined separately using linear multivariate discriminant function analysis (DFA) to probe the signature descriptors for each cohort. RESULTS: DFA indicated that glycine, sarcosine, alanine, creatine, xanthine, and hypoxanthine were able to determine abnormal prostate (BPH + PC). DFA-based classification presented high precision (86.2% by NMR and 68.1% by clinical laboratory method) in discriminating HC from BPH + PC. DFA reveals that alanine, sarcosine, creatinine, glycine, and citrate were able to discriminate PC from BPH. DFA-based categorization exhibited high accuracy (88.3% by NMR and 75.2% by clinical laboratory method) to differentiate PC from BPH. CONCLUSIONS: (1) H NMR-based metabolic profiling of filtered-serum sample appears to be assuring, swift, and least-invasive for probing and prediction of PC and BPH with its signature metabolic profile. This novel technique is not only on a par with histopathological evaluation of PC determination but is also comparable to liquid chromatography-based mass spectrometry to identify the metabolites. Prostate 76:1106-1119, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27197811 TI - Magnetism and Bond Order in Diatomic Molecules Described by Semiclassical Electrons. AB - The past decade has seen the first attempts at quantifying a semiclassical description of electrons in molecules. The challenge in this endeavor is to find potentials for electron interactions that adequately capture quantum effects. As has been the case for density functionals, the challenge is particularly great for the effects that follow from the requirement for wave function antisymmetry. Here we extend our empirical inquiry into effective potentials, from prior work on the monatomic atoms and ions of nonmetals, to diatomic molecules and ions formed by these elements. Newly adjusted and trained for the longer distances relevant to diatomics, pairwise potentials are able to fit the bond orders and magnetic properties of homonuclear species. These potentials are then found to do an excellent job of predicting the magnetism of heteronuclear species. In these molecules the predicted distribution of electrons also correctly reflects increasing ionic character with increasing difference in the electronegativities of the participating atoms. The distinctive features of the current potential are discussed, along with issues calling for further improvements. PMID- 27197813 TI - Development of gait motor control: what happens after a sudden increase in height during adolescence? AB - BACKGROUND: Basic understanding of motor control and its processes is a topic of well-known high relevance. During adolescence walking is theoretically a well achieved fundamental skill, having reached a mature manifestation; on the other hand, adolescence is marked by a period of accelerated increases in both height and weight, referred as growth spurt. Thus, this period was chosen as a controlled and natural environment for partially isolating one of the factors influencing motor development (segment growth). The aim of the study was to compare gait performance of growing and not growing male adolescents during walking in single task (ST) and dual task (DT), in order to study which are the modifications that motor control handles when encountering a sudden change in segment length. METHODS: 19 adolescents were selected as growing adolescents (they showed a height increase greater than 3 cm in 3 months). A group of BMI matched peers were selected as not growing adolescents (they showed a height increase lower than 1 cm in 3 months). Measures of acceleration of the trunk (L5 level) were collected using one tri-axial wireless inertial sensor. The participants were asked to walk at self-selected speed back and forth four times in a 10 m long corridor in ST and DT conditions. The following characteristics of gait performance were evaluated using different indices: variability, smoothness, regularity, complexity and local dynamic stability. An unpaired t-test was performed on the two groups for each method. RESULTS: Different indices followed the hypothesized trend in the two groups, even if differences were not always statistically significant: not growing adolescents showed a lower variability and complexity of gait and a higher smoothness/rhythm. Stability results showed a similarly stable gait pattern (or even higher in DT) in the growing adolescents when compared to their not growing peers. CONCLUSIONS: The findings of the present work suggest that growth spurt affects gait variability, smoothness and regularity but not gait stability. It could be argued that sudden peripheral changes of the body affect the manifestation and the performance of gait, but, on the other hand, gait control is able to handle these modifications, maintaining the stability of the system. PMID- 27197814 TI - TreesimJ: a flexible, forward time population genetic simulator. PMID- 27197812 TI - Lateralization and Binaural Interaction of Middle-Latency and Late-Brainstem Components of the Auditory Evoked Response. AB - We used magnetoencephalography to examine lateralization and binaural interaction of the middle-latency and late-brainstem components of the auditory evoked response (the MLR and SN10, respectively). Click stimuli were presented either monaurally, or binaurally with left- or right-leading interaural time differences (ITDs). While early MLR components, including the N19 and P30, were larger for monaural stimuli presented contralaterally (by approximately 30 and 36 % in the left and right hemispheres, respectively), later components, including the N40 and P50, were larger ipsilaterally. In contrast, MLRs elicited by binaural clicks with left- or right-leading ITDs did not differ. Depending on filter settings, weak binaural interaction could be observed as early as the P13 but was clearly much larger for later components, beginning at the P30, indicating some degree of binaural linearity up to early stages of cortical processing. The SN10, an obscure late-brainstem component, was observed consistently in individuals and showed linear binaural additivity. The results indicate that while the MLR is lateralized in response to monaural stimuli-and not ITDs-this lateralization reverses from primarily contralateral to primarily ipsilateral as early as 40 ms post stimulus and is never as large as that seen with fMRI. PMID- 27197815 TI - PERMANOVA-S: association test for microbial community composition that accommodates confounders and multiple distances. AB - MOTIVATION: Recent advances in sequencing technology have made it possible to obtain high-throughput data on the composition of microbial communities and to study the effects of dysbiosis on the human host. Analysis of pairwise intersample distances quantifies the association between the microbiome diversity and covariates of interest (e.g. environmental factors, clinical outcomes, treatment groups). In the design of these analyses, multiple choices for distance metrics are available. Most distance-based methods, however, use a single distance and are underpowered if the distance is poorly chosen. In addition, distance-based tests cannot flexibly handle confounding variables, which can result in excessive false-positive findings. RESULTS: We derive presence-weighted UniFrac to complement the existing UniFrac distances for more powerful detection of the variation in species richness. We develop PERMANOVA-S, a new distance based method that tests the association of microbiome composition with any covariates of interest. PERMANOVA-S improves the commonly-used Permutation Multivariate Analysis of Variance (PERMANOVA) test by allowing flexible confounder adjustments and ensembling multiple distances. We conducted extensive simulation studies to evaluate the performance of different distances under various patterns of association. Our simulation studies demonstrate that the power of the test relies on how well the selected distance captures the nature of the association. The PERMANOVA-S unified test combines multiple distances and achieves good power regardless of the patterns of the underlying association. We demonstrate the usefulness of our approach by reanalyzing several real microbiome datasets. AVAILABILITY AND IMPLEMENTATION: miProfile software is freely available at https://medschool.vanderbilt.edu/tang-lab/software/miProfile CONTACT: z.tang@vanderbilt.edu or g.chen@vanderbilt.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 27197817 TI - Dual isotope and multidetector camera: The best choices for a specific end-point. PMID- 27197816 TI - Contribution of working conditions to occupational inequalities in depressive symptoms: results from the national French SUMER survey. AB - OBJECTIVES: Social inequalities in mental health have been observed, but explanations are still lacking. The objectives were to evaluate the contribution of a large set of psychosocial work factors and other occupational exposures to social inequalities in mental health in a national representative sample of employees. METHODS: The sample from the cross-sectional national French survey SUMER 2010 included 46,962 employees: 26,883 men and 20,079 women. Anxiety and depression symptoms were measured using the Hospital Anxiety and Depression scale. Occupation was used as a marker of social position. Psychosocial work factors included various variables related to the classical job strain model, psychological demands, decision latitude, social support, and other understudied variables related to reward, job insecurity, job promotion, esteem, working time/hours, and workplace violence. Other occupational exposures of chemical, biological, physical, and biomechanical nature were also studied. Weighted age adjusted linear regression analyses were performed. RESULTS: Occupational gradients were found in the exposure to most psychosocial work factors and other occupational exposures. Occupational inequalities were observed for depressive symptoms, but not for anxiety symptoms. The factors related to decision latitude (and its sub-dimensions, skill discretion, and decision authority), social support, and reward (and its sub-dimensions, job promotion, job insecurity, and esteem) contributed to explain occupational inequalities in depressive symptoms. Decision latitude played a major role in the explanation. Workplace violence variables contributed among men only. Other exposures of physical and biomechanical nature also displayed significant contributions. CONCLUSIONS: Comprehensive prevention policies at the workplace may help to reduce social inequalities in mental health in the working population. PMID- 27197818 TI - Reducing the small-heart effect in pediatric gated myocardial perfusion single photon emission computed tomography. AB - BACKGROUND: We compared two reconstruction algorisms and two cardiac functional evaluation software programs in terms of their accuracy for estimating ejection fraction (EF) of small hearts (SH). METHODS: The study group consisted of 66 pediatric patients. Data were reconstructed using a filtered back projection (FBP) method without the resolution correction (RC) and an iterative method based on an ordered subset expectation maximization (OSEM) algorithm with the RC. EF was evaluated using two software programs of quantitative gated single-photon emission computed tomography (SPECT) (QGS) and cardioREPO. We compared the EF of gated myocardial perfusion SPECT to echocardiographic measurement (Echo). RESULTS: Forty-eight of 66 patients had an end-systolic volume < 20 mL which was used as the criterion for being included in the SH group, and the SH effect led to an overestimation of EF. While significant differences were observed between Echo (66.9 +/- 5.0%) and QGS-FBP without RC (76.9 +/- 8.4%, P < .0001), QGS-OSEM with RC (76.6 +/- 8.6%, P < .0001), and cardioREPO-FBP without RC (72.1 +/- 10.0%, P = .0011), no significant difference was observed between Echo and cardioREPO-OSEM with RC (67.4 +/- 6.1%) in SH group. CONCLUSIONS: In pediatric gated myocardial perfusion SPECT, the SH effect can be significantly reduced when an OSEM algorithm is used with RC in combination with the specific cardioREPO algorithm. PMID- 27197819 TI - The high matrix acquisition technique for imaging of atherosclerotic plaque inflammation in fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography with time-of-flight: Phantom study. AB - BACKGROUND: Motion artifact and partial volume effect caused underestimation of coronary plaque inflammation. This study evaluated the high matrix acquisition technique using time-of-flight (TOF) positron emission tomography/computed tomography for imaging of atherosclerotic plaque inflammation with fluorine-18 fluorodeoxyglucose in small and moving phantoms. METHODS AND RESULTS: All images were reconstructed using a conventional algorithm without TOF (4 * 4 * 4 mm3 voxel size) and a high matrix algorithm with TOF (2 * 2 * 2 mm3 voxel size). Microsphere phantoms of 10, 7.9, 6.2, 5.0, and 4.0 mm diameters were acquired in 3-dimensional list-mode for 30 minutes. A heart phantom mimicking cardiac motion consisted of a hot spot simulating a plaque (phi 4 mm, phi 2 mm) on the outside of the left ventricle. In the microsphere and heart phantom study, visual discrimination, maximum activity, and target-to-background ratio using the high matrix algorithm with TOF were better than those using the conventional algorithm without TOF. CONCLUSION: The high matrix algorithm with TOF improves detection of small targets in phantoms. PMID- 27197820 TI - F-18 sodium fluoride PET/CT does not effectively image myocardial inflammation due to suspected cardiac sarcoidosis. AB - BACKGROUND: Sarcoidosis is an inflammatory disorder of unknown etiology that can involve the heart. While effective in imaging cardiac sarcoidosis, F-18 fluorodeoxyglucose (FDG) PET/CT often shows non-specific myocardial uptake. F-18 sodium fluoride (NaF) has been used to image inflammation in coronary artery plaques and has low background myocardial uptake. Here, we evaluated whether F-18 NaF can image myocardial inflammation due to clinically suspected cardiac sarcoidosis. PATIENTS AND METHODS: We performed a single institution pilot study testing if F-18 NaF PET/CT can detect myocardial inflammation in patients with suspected cardiac sarcoidosis. Patients underwent cardiac PET/CT with F-18 FDG as part of their routine care and subsequently received an F-18 NaF PET/CT scan. RESULTS: Three patients underwent F-18 FDG and F-18 NaF imaging. In all patients, there was F-18 FDG uptake consistent with cardiac sarcoidosis. The F-18 NaF PET/CT scans showed no myocardial uptake. CONCLUSIONS: In this small preliminary study, PET/CT scan using F-18 NaF does not appear to detect myocardial inflammation caused by suspected cardiac sarcoidosis. PMID- 27197821 TI - The Relationship between the Supervision Role and Compassion Fatigue and Burnout in Genetic Counseling. AB - Many genetic counselors provide supervision to students during their career. Previous studies have shown genetic counselors, in general, are at increased risk for developing compassion fatigue. The purpose of this study was to determine if there was a difference in compassion fatigue and burnout levels in genetic counselors who currently supervise compared to genetic counselors who do not. Genetic counselors who currently practice in a clinical setting (N = 391) completed an online survey containing demographic questions, the Professional Quality of Life Scale, the State-Trait Anxiety Inventory, and questions specific to the genetic counselor's experiences with supervision. Overall, when controlling for trait-anxiety, the supervision role by itself was not independently associated with the risk for compassion fatigue and burnout among genetic counselors. Within supervisors, however, there were several factors which were associated with this risk. Those with less supervision experience reported more secondary traumatic stress. Those supervisors reporting less confidence had decreased compassion satisfaction. Those with less experience or less confidence in their supervision role were most likely to be at increased risk for developing compassion fatigue. Training in supervision and support for dealing with compassion fatigue and burnout may be beneficial to supervisors with less experience. PMID- 27197822 TI - [Diseases of the acromioclavicular joint]. AB - The acromioclavicular joint together with the sternoclavicular joint represents the only articulation between the shoulder girdle, the upper extremities and the trunk. The high load on the relative small joint surface results in a high risk for degenerative changes. The most common pathology is therefore osteoarthritis. In addition, joint instability and many inflammatory processes can occur, especially rheumatoid type pathologies and metabolic disorders. Acromioclavicular cysts represent a clinically evident disease, which are frequently associated with an underlying cuff tear arthropathy. A thorough clinical examination supported by appropriate imaging allows a rapid and reliable diagnosis. Conservative therapy is usually symptom related. Surgical procedures after failed conservative therapy must be specific for the pathology in question and are successful in most cases. PMID- 27197823 TI - [Characteristics of neuromuscular scoliosis]. AB - Usually, neuromuscular scolioses become clinically symptomatic relatively early and are rapidly progressive even after the end of growth. Without sufficient treatment they lead to a severe reduction of quality of life, to a loss of the ability of walking, standing or sitting as well as to an impairment of the cardiopulmonary system resulting in an increased mortality. Therefore, an intensive interdisciplinary treatment by physio- and ergotherapists, internists, pediatricians, orthotists, and orthopedists is indispensable. In contrast to idiopathic scoliosis the treatment of patients with neuromuscular scoliosis with orthosis is controversially discussed, whereas physiotherapy is established and essential to prevent contractures and to maintain the residual sensorimotor function.Frequently, the surgical treatment of the scoliosis is indicated. It should be noted that only long-segment posterior correction and fusion of the whole deformity leads to a significant improvement of the quality of life as well as to a prevention of a progression of the scoliosis and the development of junctional problems. The surgical intervention is usually performed before the end of growth. A prolonged delay of surgical intervention does not result in an increased height but only in a deformity progression and is therefore not justifiable. In early onset neuromuscular scolioses guided-growth implants are used to guarantee the adequat development. Because of the high complication rates, further optimization of these implant systems with regard to efficiency and safety have to be addressed in future research. PMID- 27197825 TI - Fitkids Treadmill Test: Age- and Sex-Related Normative Values in Dutch Children and Adolescents. AB - BACKGROUND: Recent research has shown that the Fitkids Treadmill Test (FTT) is a valid and reproducible exercise test for the assessment of aerobic exercise capacity in children and adolescents who are healthy. OBJECTIVE: The study objective was to provide sex- and age-related normative values for FTT performance in children and adolescents who were healthy, developing typically, and 6 to 18 years of age. DESIGN: This was a cross-sectional, observational study. METHODS: Three hundred fifty-six children and adolescents who were healthy (174 boys and 182 girls; mean age=12.9 years, SD=3.7) performed the FTT to their maximal effort to assess time to exhaustion (TTE). The least-mean-square method was used to generate sex- and age-related centile charts (P3, P10, P25, P50, P75, P90, and P97) for TTE on the FTT. RESULTS: In boys, the reference curve (P50) showed an almost linear increase in TTE with age, from 8.8 minutes at 6 years of age to 16.1 minutes at 18 years of age. In girls, the P50 values for TTE increased from 8.8 minutes at 6 years of age to 12.5 minutes at 18 years of age, with a plateau in TTE starting at approximately 10 years of age. LIMITATIONS: Youth who were not white were underrepresented in this study. CONCLUSIONS: This study describes sex- and age-related normative values for FTT performance in children and adolescents who were healthy, developing typically, and 6 to 18 years of age. These age- and sex-related normative values will increase the usefulness of the FTT in clinical practice. PMID- 27197824 TI - Joint-Specific Play Controller for Upper Extremity Therapy: Feasibility Study in Children With Wrist Impairment. AB - BACKGROUND: Challenges with any therapeutic program for children include the level of the child's engagement or adherence. Capitalizing on one of the primary learning avenues of children, play, the approach described in this article is to develop therapeutic toy and game controllers that require specific and repetitive joint movements to trigger toy/game activation. OBJECTIVE: The goal of this study was to evaluate a specially designed wrist flexion and extension play controller in a cohort of children with upper extremity motor impairments (UEMIs). The aim was to understand the relationship among controller play activity, measures of wrist and forearm range of motion (ROM) and spasticity, and ratings of fun and difficulty. DESIGN: This was a cross-sectional study of 21 children (12 male, 9 female; 4-12 years of age) with UEMIs. METHODS: All children participated in a structured in-clinic play session during which measurements of spasticity and ROM were collected. The children were fitted with the controller and played with 2 toys and 2 computer games for 5 minutes each. Wrist flexion and extension motion during play was recorded and analyzed. In addition, children rated the fun and difficulty of play. RESULTS: Flexion and extension goal movements were repeatedly achieved by children during the play session at an average frequency of 0.27 Hz. At this frequency, 15 minutes of play per day would result in approximately 1,700 targeted joint motions per week. Play activity was associated with ROM measures, specifically supination, but toy perception ratings of enjoyment and difficulty were not correlated with clinical measures. LIMITATIONS: The reported results may not be representative of children with more severe UEMIs. CONCLUSIONS: These outcomes indicate that the therapeutic controllers elicited repetitive goal movements and were adaptable, enjoyable, and challenging for children of varying ages and UEMIs. PMID- 27197827 TI - Icelandic Physical Therapists' Attitudes Toward Adoption of New Knowledge and Evidence-Based Practice: Cross-Sectional Web-Based Survey. AB - BACKGROUND: A positive attitude toward evidence-based practice (EBP) has been identified as an important factor in the effectiveness of the dissemination and implementation of EBP in real-world settings. OBJECTIVE: The objectives of this study were: (1) to describe dimensions of Icelandic physical therapists' attitudes toward the adoption of new knowledge and EBP and (2) to explore the association between attitudes and selected personal and environmental factors. DESIGN: This study was a cross-sectional, Web-based survey of the total population of full members of the Icelandic Physiotherapy Association. METHODS: The Evidence-Based Practice Attitude Scale (EBPAS) was used to survey attitudes toward EBP; the total EBPAS and its 4 subscales (requirements, appeal, openness, and divergence) were included. Linear regression was used to explore the association between the EBPAS and selected background variables. RESULTS: The response rate was 39.5% (N=211). The total EBPAS and all of its subscales reflected physical therapists' positive attitudes toward the adoption of new knowledge and EBP. Multivariable analysis revealed that being a woman was associated with more positive attitudes, as measured by the total EBPAS and the requirements, openness, and divergence subscales. Physical therapists with postprofessional education were more positive, as measured by the EBPAS openness subscale, and those working with at least 10 other physical therapists demonstrated more positive attitudes on the total EBPAS and the openness subscale. LIMITATIONS: Because this was a cross-sectional survey, no causal inferences can be made, and there may have been unmeasured confounding factors. Potential nonresponse bias limits generalizability. CONCLUSIONS: The results expand understanding of the phenomenon of attitudes toward EBP. They reveal potentially modifiable dimensions of attitudes and the associated characteristics of physical therapists and their work environments. The findings encourage investigation of the effectiveness of strategies aimed at influencing various dimensions of attitudes toward EBP. PMID- 27197826 TI - Physical Rehabilitation Interventions for Post-mTBI Symptoms Lasting Greater Than 2 Weeks: Systematic Review. AB - BACKGROUND: Heightened awareness of the lasting effects of mild traumatic brain injury (mTBI) has amplified interest in interventions that facilitate recovery from persistent post-mTBI symptoms. PURPOSE: The purpose of this study was to systematically review the literature to identify potential physical rehabilitation interventions that are safe, feasible, and appropriate for physical therapists to utilize with patients with persistent mTBI-related symptoms. DATA SOURCES: The electronic databases PubMed, Cochrane Library, CINAHL, Scopus, SPORTDiscus, and Web of Science were systematically searched from database inception until June 2015. STUDY SELECTION: Studies were included if they utilized physical rehabilitation interventions and the study's participants had a diagnosis of mTBI, a mean age of 8 years or older, and symptoms persisting an average of 2 weeks or longer. Exclusion criteria included blast injuries, diagnosis of moderate or severe TBI, or psychosis. DATA EXTRACTION: Data extraction and methodological risk of bias assessments were performed for each study. DATA SYNTHESIS: Eight studies with a range of study designs, intervention types, and outcome measures were included. The interventions investigated by the included studies were categorized into 3 types: physiological, vestibulo-ocular, and cervicogenic. LIMITATIONS: The identified studies had several significant limitations including: small sample sizes and low-level study designs. CONCLUSIONS: The results of this systematic review indicate that several physical rehabilitation options with minimal risk for negative outcomes are available for treating patients experiencing persistent post-mTBI symptoms. These options include: vestibular, manual, and progressive exercise interventions. Conclusions surrounding efficacy and ideal dosing parameters for these interventions are limited at this time due to the small number of studies, the range of interventional protocols, and lower levels of study design. PMID- 27197828 TI - Understanding the Relationship Between Physical Therapist Participation in Interdisciplinary Rounds and Hospital Readmission Rates: Preliminary Study. AB - BACKGROUND: Providing patients with optimal discharge disposition and follow-up services could prevent unplanned readmissions. Despite their qualifications, physical therapists are rarely represented on the interdisciplinary team. OBJECTIVE: This study aimed to determine the relationship between the participation of physical therapists in interdisciplinary discharge rounds and readmission rates. METHODS: In this retrospective observational study, patients discharged by 2 interdisciplinary teams with or without a physical therapist's participation were followed for 5 months. Adherence to the physical therapist's recommendations for follow-up services and unplanned 30-day readmissions were tracked. Multiple logistic regression and random forest models were used to determine factors contributing to 30-day readmission rates. RESULTS: The odds of 30-day readmissions were 3.78 times greater when a physical therapist was absent from the interdisciplinary team compared with the odds of 30-day readmissions when a physical therapist participated in the interdisciplinary team. In addition, the odds of 30-day readmission for patients discharged to their home were 2.47 times greater than those who were not discharged to their home. An increased lack of postdischarge services was noted when a physical therapist was not included in the interdisciplinary team. LIMITATIONS: The nonrandom selection of patients into groups, the small sample size, and the inability to adjust risk for unknown factors (eg, medical diagnoses, comorbidities, funding, and functional measures) limited interpretation of the results. CONCLUSION: Significantly higher readmission rates were noted for patients whose interdisciplinary team did not have a physical therapist and for those patients who were discharged to their home. These preliminary findings suggest that discharge from the acute care setting is an elaborate process and should be designed carefully. In order to identify the optimal discharge process, future research should account for patient complexities in addition to the composition of the interdisciplinary discharge team. PMID- 27197829 TI - Randomized Controlled Trial for Evaluation of the Routine Use of Nasogastric Tube Decompression After Elective Liver Surgery. AB - BACKGROUND: The value of routine nasogastric tube (NGT) decompression after elective hepatetctomy is not yet established. Previous studies in the setting of non-liver abdominal surgery suggested that the use of NGT decreased the incidence of nausea or vomiting, while increasing the frequency of pulmonary complications. STUDY DESIGN: Out of a total of 284 consecutive patients undergoing hepatectomy, 210 patients were included in this study. The patients were randomized to a group that received NGT decompression (NGT group; n = 108), in which a NGT was left in place after surgery until the patient passed flatus or stool, or a group that did not receive NGT decompression (no-NGT group; n = 102), in which the NGT was removed at the end of surgery. RESULTS: There were no differences between the NGT group and no-NGT group in terms of the overall morbidity (34.3 vs 35.3 %; P = 0.99), incidence of pulmonary complications (18.5 vs 19.5 %; P = 0.84), frequency of postoperative vomiting (6.5 vs 7.8 %; P = 0.70), time to start of oral intake (median (range) 3 (2-6) vs 3 (2-6) days; P = 0.69), or postoperative duration of hospital stay (19 (7-74) vs 18 (9-186) days; P = 0.37). In the no-NGT group, three patients required reinsertion of the tube 0 (0-3) days after surgery. In the NGT group, severe discomfort was recorded in five patients. CONCLUSIONS: Routine NGT decompression after elective hepatectomy does not appear to have any advantages. PMID- 27197830 TI - Food Price Policies May Improve Diet but Increase Socioeconomic Inequalities in Nutrition. AB - Unhealthy eating is more prevalent among women and people with a low socioeconomic status. Policies that affect the price of food have been proposed to improve diet quality. The study's objective was to compare the impact of food price policies on the nutritional quality of food baskets chosen by low-income and medium-income women. Experimental economics was used to simulate a fruit and vegetable subsidy and a mixed policy subsidizing healthy products and taxing unhealthy ones. Food classification was based on the Score of Nutritional Adequacy of Individual Foods, Score of Nutrients to Be Limited nutrient profiling system. Low-income (n = 95) and medium-income (n = 33) women selected a daily food basket first at current prices and then at policy prices. Energy density (ED) and the mean adequacy ratio (MAR) were used as nutritional quality indicators. At baseline, low-income women selected less healthy baskets than medium-income women (less fruit and vegetables, more unhealthy products, higher ED, lower MAR). Both policies improved nutritional quality (fruit and vegetable quantities increased, ED decreased, the MAR increased), but the magnitude of the improvement was often lower among low-income women. For instance, ED decreased by 5.3% with the fruit and vegetable subsidy and by 7.3% with the mixed subsidy, whereas decreases of 13.2 and 12.6%, respectively, were recorded for the medium income group. Finally, both policies improved dietary quality, but they increased socioeconomic inequalities in nutrition. PMID- 27197832 TI - Effect of apelin hormone on renal ischemia/reperfusion induced oxidative damage in rats. AB - Apelin is a peptide hormone defined as a ligand for G-protein clamped receptor (APJ) receptor. It is indicated in the literature both apelin and APJ are synthesized on the peripheral tissues including the renal tissues. Which roles does the apelin play on the renal tissue has not been completely illuminated yet. This study is designed to determine the possible protective effect of apelin-13 on the kidney I/R injury. Adult male Sprague-Dawley rats were used in this study. In the sham group, right kidneys of the animals were dissected. In the I/R group, right kidney was dissected and ischemia of 45 min was performed, and then reperfusion was applied for 3 h. In the treatment groups, three different doses of apelin were injected at the beginning of the ischemia unlike the I/R group. BUN, Cre, Na, K, Cl, total protein and albumin from serum samples were determined and TNF-alpha, IL-1beta, IL-6, TAS and TOS parameters were read with ELISA reader. MDA, SOD, CAT and GSH-Px enzyme activations from renal tissues were measured. In comparison with the sham and I/R groups, while the serum BUN, CRE, CI and TNF-alpha levels showed an increase in the groups on which the apelin-13 was applied, Na, total protein, albumin, TAS levels decreased. Serum TOS level of other groups showed an increase by comparison with the sham group. Our results showed that apelin-13 applied after I/R increased the antioxidant enzyme activity in a dose dependent manner, prevented the lipid oxidation and improved the renal functions. PMID- 27197833 TI - Effect of Genome Position on Heterologous Gene Expression in Bacillus subtilis: An Unbiased Analysis. AB - A fixed gene copy number is important for the in silico construction of engineered synthetic networks. However, the copy number of integrated genes depends on their genomic location. This gene dosage effect is rarely addressed in synthetic biology. Two studies in Escherichia coli presented conflicting data on the impact of gene dosage. Here, we investigate how genome location and gene orientation influences expression in Bacillus subtilis. An important difference with the E. coli studies is that we used an unbiased genome integration approach mediated by random transposon insertion. We found that there is a strong gene dosage effect in fast growing B. subtilis cells, which can amount to a 5-fold difference in gene expression. In contrast, gene orientation with respect to DNA replication direction does not influence gene expression. Our study shows that gene dosage should be taken into account when designing synthetic circuits in B. subtilis and presumably other bacteria. PMID- 27197831 TI - Sex-dependent mitochondrial respiratory impairment and oxidative stress in a rat model of neonatal hypoxic-ischemic encephalopathy. AB - Increased male susceptibility to long-term cognitive deficits is well described in clinical and experimental studies of neonatal hypoxic-ischemic encephalopathy. While cell death signaling pathways are known to be sexually dimorphic, a sex dependent pathophysiological mechanism preceding the majority of secondary cell death has yet to be described. Mitochondrial dysfunction contributes to cell death following cerebral hypoxic-ischemia (HI). Several lines of evidence suggest that there are sex differences in the mitochondrial metabolism of adult mammals. Therefore, this study tested the hypothesis that brain mitochondrial respiratory impairment and associated oxidative stress is more severe in males than females following HI. Maximal brain mitochondrial respiration during oxidative phosphorylation was two-fold more impaired in males following HI. The endogenous antioxidant glutathione was 30% higher in the brain of sham females compared to males. Females also exhibited increased glutathione peroxidase (GPx) activity following HI injury. Conversely, males displayed a reduction in mitochondrial GPx4 protein levels and mitochondrial GPx activity. Moreover, a 3-4-fold increase in oxidative protein carbonylation was observed in the cortex, perirhinal cortex, and hippocampus of injured males, but not females. These data provide the first evidence for sex-dependent mitochondrial respiratory dysfunction and oxidative damage, which may contribute to the relative male susceptibility to adverse long term outcomes following HI. Lower basal GSH levels, lower post-hypoxic mitochondrial glutathione peroxidase (mtGPx) activity, and mitochondrial glutathione peroxidase 4 (mtGPx4) protein levels may contribute to the susceptibility of the male brain to oxidative damage and mitochondrial dysfunction following neonatal hypoxic-ischemia (HI). Treatment of male pups with acetyl-L-carnitine (ALCAR) protects against the loss of mtGPx activity, mtGPx4 protein, and increases in protein carbonylation after HI. These findings provide novel insight into the pathophysiology of sexually dimorphic outcomes following HI. PMID- 27197834 TI - AhR signaling activation disrupts migration and dendritic growth of olfactory interneurons in the developing mouse. AB - Perinatal exposure to a low level of dioxin, a ubiquitous environmental pollutant, has been shown to induce abnormalities in learning and memory, emotion, and sociality in laboratory animals later in adulthood. However, how aryl hydrocarbon receptor (AhR) signaling activation disrupts the higher brain function remains unclear. Therefore, we studied the possible effects of excessive activation of AhR signaling on neurodevelopmental processes, such as cellular migration and neurite growth, in mice. To this end, we transfected a constitutively active-AhR plasmid into stem cells in the lateral ventricle by in vivo electroporation on postnatal day 1. Transfection was found to induce tangential migration delay and morphological abnormalities in neuronal precursors in the rostral migratory stream at 6 days post-electroporation (dpe) as well as disrupt radial migration in the olfactory bulb and apical and basal dendritic growth of the olfactory interneurons in the granule cell layer at 13 and 20 dpe. These results suggest that the retarded development of interneurons by the excessive AhR signaling may at least in part explain the dioxin-induced abnormal behavioral alterations previously reported in laboratory animals. PMID- 27197836 TI - Dronedarone and Amiodarone Induce Dyslipidemia and Thyroid Dysfunction in Rats. AB - BACKGROUND/AIMS: Amiodarone, a thyroid hormone-like molecule, can induce dyslipidemia and thyroid dysfunction. However, the effects of dronedarone on lipid metabolism and of both dronedarone and amiodarone on thyroid function and lipid metabolism remain unknown. METHODS: Fifty male Sprague-Dawley rats were randomly divided into 5 groups (10 in each group): normal control (NC), amiodarone-treated (AMT), dronedarone-treated (DRT), rats treated with amiodarone combined with polyene phosphatidylcholine (AC), and rats treated with dronedarone combined with polyene phosphatidylcholine (DC). Rats were given amiodarone (120 mg/kg/d), dronedarone (120 mg/kg/d), and polyene phosphatidylcholine (200 mg/kg/d) for 13 weeks. At the end of weeks 4, 8, 12, and 13, plasma-free triiodothyronine (FT3), free thyroxine (FT4), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) were determined. At the end of this protocol, rats were sacrificed and the thyroid glands were isolated, weighed, and examined histopathologically. The protein expression of Bcl-2 was measured by immunochemical staining. The mRNA expression of thyroglobulin (Tg), type-1 deiodinase (D1), and thyroid peroxidase (TPO) were detected by polymerase chain reaction (PCR). RESULTS: Compared with the NC group, FT3 and FT4 levels in the DRT and DC groups significantly increased at week 4 but declined thereafter. The AMT and AC groups had lower FT3 levels but comparable FT4 levels. The levels of TG, LDL-c, and HDL-c in the NC group were lower than those in the other groups whereas the LDL-c/HDL-c ratio was lowest in the AMT group. Bcl-2 expression significantly increased in the DRT group. The mRNA expression of Tg increased whereas the mRNA expression of D1 decreased. Dronedarone induced hyperthyroidism at the early stage and hypothyroidism at the late stage whereas amiodarone only caused hypothyroidism. CONCLUSION: Both dronedarone and amiodarone can induce dyslipidemia and increase the levels of TC, LDL-c, and HDL-c, and these effects may be associated with thyroid dysfunction. PMID- 27197837 TI - Genetically Engineered Crops and Certified Organic Agriculture for Improving Nutrition Security in Africa and South Asia. AB - In Africa and South Asia, where nutrition insecurity is severe, two of the most prominent production technologies are genetically modified (GM) crops and certified organic agriculture. We analyze the potential impact pathways from agricultural production to nutrition. Our review of data and the literature reveals increasing farm-level income from cash crop production as the main pathway by which organic agriculture and GM agriculture improve nutrition. Potential secondary pathways include reduced prices of important food crops like maize due to GM maize production and increased food production using organic technology. Potential tertiary pathways are improvements in health due to reduced insecticide use. Challenges to the technologies achieving their impact include the politics of GM agriculture and the certification costs of organic agriculture. Given the importance of agricultural production in addressing nutrition security, accentuated by the post-2015 sustainable development agenda, the chapter concludes by stressing the importance of private and public sector research in improving the productivity and adoption of both GM and organic crops. In addition, the chapter reminds readers that increased farm income and productivity require complementary investments in health, education, food access and women's empowerment to actually improve nutrition security. PMID- 27197835 TI - Tiotropium safety in 'real-world' populations: Response to Schmiedl, et al. in the British Journal of Clinical Pharmacology. PMID- 27197839 TI - Modified anaerobic digestion elutriated phased treatment for the anaerobic co digestion of sewage sludge and food wastewater. AB - A modified anaerobic digestion elutriated phased treatment (MADEPT) process was developed for investigating anaerobic co-digestion of sewage sludge and food wastewater. The anaerobic digestion elutriated phased treatment (ADEPT) process is similar to a two-phase system, however, in which the effluent from a methanogenic reactor recycles into an acidogenic reactor to elutriate mainly dissolved organics. Although ADEPT could reduce reactor volume significantly, the unsolubilized solids should be wasted from the system. The MADEPT process combines thermo-alkali solubilization with ADEPT to improve anaerobic performance and to minimize the sludge disposal. It was determined that the optimal volume mixing ratio of sewage sludge and food wastewater was 4 : 1 for the anaerobic co digestion. The removal efficiencies of total chemical oxygen demand, volatile solids, and volatile suspended solids in the MADEPT process were 73%, 70%, and 64%, respectively. However, those in the ADEPT process were only 48%, 37%, and 40%, respectively, at the same hydraulic retention time (HRT) of 7 days. The gas production of MADEPT was two times higher than that of ADEPT. The thermo-alkali solubilization increased the concentration of dissolved organics so that they could be effectively degraded in a short HRT, implying that MADEPT could improve the performance of ADEPT in anaerobic co-digestion. PMID- 27197838 TI - Ratiometric Nanothermometer Based on Rhodamine Dye-Incorporated F127-Melamine Formaldehyde Polymer Nanoparticle: Preparation, Characterization, Wide-Range Temperature Sensing, and Precise Intracellular Thermometry. AB - A series of fluorescent nanothermometers (FTs) was prepared with Rhodamine dye incorporated Pluronic F-127-melamine-formaldehyde composite polymer nanoparticles (R-F127-MF NPs). The highly soluble Rhodamine dye molecules were bound with Pluronic F127 micelles and subsequently incorporated in the cross-linked MF resin NPs during high-temperature cross-link treatment. The morphology and chemical structure of R-F127-MF NPs were characterized with dynamic light scattering, electron microscopy, and Fourier-transform infrared (FTIR) spectra. Fluorescence properties and thermoresponsivities were analyzed using fluorescence spectra. R F127-MF NPs are found to be monodispersed, presenting a size range of 88-105 nm, and have bright fluorescence and high stability in severe treatments such as autoclave sterilization and lyophilization. By simultaneously incorporating Rhodamine B and Rhodamine 110 (as reference) dyes at a doping ratio of 1:400 in the NPs, ratiometric FTs with a high sensibility of 7.6%. degrees C(-1) and a wide temperature sensing range from -20 to 110 degrees C were obtained. The FTs exhibit good stability in solutions with varied pH, ionic strengths, and viscosities and have similar working curves in both intracellular and extracellular environments. Cellular temperature variations in Hela cells during microwave exposure were successfully monitored using the FTs, indicating their considerable potential applications in the biomedical field. PMID- 27197840 TI - Ambulatory Activity Components Deteriorate Differently across Neurodegenerative Diseases: A Cross-Sectional Sensor-Based Study. AB - BACKGROUND AND PURPOSE: Reduced ambulatory activity is a major burden in neurodegenerative disease (NDD), leading to severe restrictions in social participation and further deterioration of motor capacities. However, objective evidence on walking behavior patterns and components underlying this impairment and its decline with disease progression is scarce for many NDDs. We aimed to unravel the detailed metrics underlying the reduced ambulatory activity in selected NDDs, and their relation to disease duration. We hypothesized that progressively reduced ambulatory activity is a feature shared across different NDDs, characterized by changes in both common and distinct components. METHODS: Sixty-five subjects with NDD (n = 34 degenerative ataxia; n = 15 progressive supranuclear palsy, and n = 16 Parkinson's disease) and 38 healthy older adults (total n = 103) wore a three-axial accelerometer (activPAL3TM) for 7 consecutive days. Detailed metrics of ambulatory activity were calculated. RESULTS: The average daily walking duration was significantly decreased in all three NDDs, yet characterized by a differential pattern of changes in number and length of walking bouts and sit-to-stand transfers. Decline in walking duration progressed with increased disease duration in all three NDDs, yet at a differing rate. This decline was associated with progressive reductions in walking bout length and walking behavior pattern diversity in all three NDDs. CONCLUSIONS: These findings provide objective evidence that reduced ambulatory activity is a shared feature across different NDDs. Moreover, they reveal that several underlying walking behavior components change with increasing disease duration, yet at a differing rate in different NDDs. This indicates that metric analysis of ambulatory activity might provide ecologically relevant and disease-specific progression and outcome markers in several NDDs. PMID- 27197841 TI - The role of learning in social development: Illustrations from neglected children. AB - Children who experience early caregiving neglect are very likely to have problems developing and maintaining relationships and regulating their social behavior. One of the earliest manifestations of this problem is reflected in indiscriminate behavior, a phenomenon where young children do not show normative wariness of strangers or use familiar adults as sources of security. To better understand the developmental mechanisms underlying the emergence of these problems, this study examined whether institutionally reared children, who experienced early social neglect, had difficulty associating motivational significance to visual stimuli. Pairing stimuli with motivational significance is presumably one of the associative learning processes involved in establishing discriminate or selective relationships with others. We found that early experiences of neglectful caregiving were associated with difficulties in acquiring such associations, and that delays in this developmental skill were related to children's social difficulties. These data suggest a way in which early social learning experiences may impact the development of processes underlying emotional development. PMID- 27197842 TI - Theragnostic ultrasound using microbubbles in the treatment of prostate cancer. AB - The use of gas-filled microbubbles in perfusion monitoring as intravascular ultrasound contrast agents has recently become more common. Additionally, microbubbles are employed as carriers of pharmaceutical substances or genes. Microbubbles have great potential to improve the delivery of therapeutic materials into cells and to modify vascular permeability, causing increased extravasation of drugs and drug carriers. Prostate cancer is the most common neoplasm in Europe and America, with an incidence twice to three times that of lung and colorectal cancer. Its incidence is still rising in Asian countries, including Japan and Korea. In this review, we present current strategies regarding the synthesis of microbubbles with targeted ligands on their surfaces, with a focus on prostate cancer. PMID- 27197843 TI - Preventive effects of citrulline on Western diet-induced non-alcoholic fatty liver disease in rats. AB - A Western diet induces insulin resistance, liver steatosis (non-alcoholic fatty liver disease (NAFLD)) and intestinal dysbiosis, leading to increased gut permeability and bacterial translocation, thus contributing to the progression of NAFLD to non-alcoholic steatohepatitis. In the present study, we sought, in a model of Western diet-induced NAFLD, to determine whether citrulline (Cit), an amino acid that regulates protein and energy metabolism, could decrease Western diet-induced liver injuries, as well as the mechanisms involved. Sprague-Dawley rats were fed a high-fat diet (45 %) and fructose (30 %) in drinking water or a control diet associated with water (group C) for 8 weeks. The high-fat, high fructose diet (Western diet) was fed either alone (group WD) or with Cit (1 g/kg per d) (group WDC) or an isonitrogenous amount of non-essential amino acids (group WDA). We evaluated nutritional and metabolic status, liver function, intestinal barrier function, gut microbiota and splanchnic inflammatory status. Cit led to a lower level of hepatic TAG restricted to microvesicular lipid droplets and to a lower mRNA expression of CCAAT-enhancer-binding protein homologous protein, a marker of endoplasmic reticulum stress, of pro-inflammatory cytokines Il6 (P<0.05) and Tnfalpha, and of toll-like receptor 4 (Tlr4) (P<0.05). Cit also improved plasma TAG and insulin levels. In the colon, it decreased inflammation (Tnfalpha and Tlr4 expressions) and increased claudin-1 protein expression. This was associated with higher levels of Bacteroides/Prevotella compared with rats fed the Western diet alone. Cit improves Western diet-induced liver injuries via decreased lipid deposition, increased insulin sensitivity, lower inflammatory process and preserved antioxidant status. This may be related in part to its protective effects at the gut level. PMID- 27197844 TI - Optically Active Liquid Crystalline Polyoxometalates via Electrostatic Encapsulation with Cholesterol-Containing Amphiphile. AB - A novel cholesterol-containing amphiphile was designed and prepared in the study, which is a room-temperature ionic liquid crystal over a broad temperature range with pronounced chiroptical properties. Four types of inorganic polyoxometalates (PMs) with different numbers of charges were encapsulated by the chiral amphiphile. The incorporation of chiral organic cations triggers achiral PMs in the complexes to show induced chirality through intermolecular interactions, as demonstrated by circular dichroism spectroscopy. The electrostatic encapsulation with mesomorphic promoters provides the inorganic PMs with liquid crystalline behavior, characterized by differential scanning calorimetry, polarized optical microscopy, and X-ray diffraction. The strategy applied herein represents a unique example of liquid crystalline PM complexes with optical activity. PMID- 27197846 TI - Novel polyazamacrocyclic receptor decorated core-shell superparamagnetic microspheres for selective binding and magnetic enrichment of palladium: synthesis, adsorptive behavior and coordination mechanism. AB - The development of economical and green technologies for the effective recovery of palladium has attracted worldwide attention in recent years. Magnetic separation involving the use of functional magnetic nanoparticles (MNPs) with superparamagnetic characteristics holds great promise in this respect. This study presents a novel class of core-shell structured superparamagnetic microspheres decorated with polyazamacrocyclic receptors, which show a highly-selective binding to Pd(ii) in HNO3 media. The superparamagnetic microspheres possess a high saturation magnetization (53.8 emu g(-1)) and high adsorption capacity (qmax~ 105.3 MUmol g(-1)), affording efficient enrichment and fast separation (within 13 seconds) of palladium under an applied magnetic field. Adsorptive behavior was fully investigated combined with the corresponding theoretical analysis by using kinetic equations and Langmuir/Freundlich isotherm models. Moreover, the coordination mechanism of the polyazamacrocyclic receptors to Pd(ii) was carefully examined based on high resolution X-ray photoelectron spectroscopy (XPS) and FT-IR spectrophotometry. A suggested mechanism involving the synergistic effect of the cyclic amines and carboxyl arms of the polyazamacrocyclic receptors was proposed to describe the coordination manner, while explaining the selectivity to Pd(ii) in HNO3 solutions. From a practical perspective, the Pd(ii)-enriched microspheres could be readily regenerated for cycle use. We conclude that this kind of polyazamacrocyclic receptor decorated superparamagnetic microsphere is of potential use for the effective recovery of Pd(ii) as well as other precious metals. PMID- 27197845 TI - Promoting the bio-cathode formation of a constructed wetland-microbial fuel cell by using powder activated carbon modified alum sludge in anode chamber. AB - MFC centered hybrid technologies have attracted attention during the last few years due to their compatibility and dual advantages of energy recovery and wastewater treatment. In this study, a MFC was integrated into a dewatered alum sludge (DAS)- based vertical upflow constructed wetland (CW). Powder activate carbon (PAC) was used in the anode area in varied percentage with DAS to explore its influences on the performance of the CW-MFC system. The trial has demonstrated that the inclusion of PAC improved the removal efficiencies of COD, TN and RP. More significantly, increasing the proportion of PAC from 2% to 10% can significantly enhance the maximum power densities from 36.58 mW/m(2) to 87.79 mW/m(2). The induced favorable environment for bio-cathode formation might be the main reason for this improvement since the content of total extracellular polymeric substances (TEPS) of the substrate in the cathode area almost doubled (from 44.59 MUg/g wet sludge to 87.70 MUg/g wet sludge) as the percentage of PAC increased to 10%. This work provides another potential usage of PAC in CW-MFCs with a higher wastewater treatment efficiency and energy recovery. PMID- 27197847 TI - Chest and neck pain in a 22 year old woman. PMID- 27197848 TI - Endovascular Hypothermia in Acute Ischemic Stroke: Pilot Study of Selective Intra Arterial Cold Saline Infusion. AB - BACKGROUND AND PURPOSE: We conducted a pilot feasibility and safety study of selective brain cooling with intra-arterial infusion of cold saline combined with endovascular reperfusion for acute ischemic stroke. METHODS: Patients with large vessel occlusion within 8 hours after symptom onset were enrolled. All patients received intra-arterial recanalization combined with infusion of cold isotonic saline (4 degrees C) in the ischemic territory through the angiographic catheter. RESULTS: Twenty-six patients underwent the procedure, which was technically successful in all. The temperature of ischemic cerebral tissue was decreased by at least 2 degrees C during infusion of the cold solution, and systemic temperature was mildly reduced (maximum 0.3 degrees C). No obvious complications related to intra-arterial hypothermia were observed. CONCLUSIONS: Selective brain cooling by intra-arterial infusion of cold saline combined with endovascular recanalization therapy in acute ischemic stroke seems feasible and safe. PMID- 27197849 TI - Procalcitonin and Midregional Proatrial Natriuretic Peptide as Markers of Ischemic Stroke: The Northern Manhattan Study. AB - BACKGROUND AND PURPOSE: Chronic infections and neuroendocrine dysfunction may be risk factors for ischemic stroke (IS). We hypothesized that selected blood biomarkers of infection (procalcitonin [PCT]), hypothalamic-pituitary-axis function (copeptin), and hemodynamic dysfunction (midregional proatrial natriuretic peptide [MRproANP]) are associated with incident IS risk in the multiethnic, urban Northern Manhattan Study (NOMAS) cohort. METHODS: A nested case-control study was performed among initially stroke-free participants. Cases were defined as first IS (n=172). We randomly selected controls among those who did not develop an event (n=344). We calculated Cox proportional hazards models with inverse probability weighting to estimate the association of blood biomarkers with risk of stroke after adjusting for demographic, behavioral, and medical risk factors. RESULTS: Those with PCT and MRproANP, but not copeptin, in the top quartile, compared with the lowest quartile, were associated with IS (for PCT adjusted hazard ratio [HR], 1.9; 95% confidence interval [CI], 1.0-3.8 and for MRproANP adjusted HR, 3.5; 95% CI, 1.6-7.5). The associations of PCT and MRproANP differed by stroke etiology; PCT levels in the top quartile were particularly associated with small vessel stroke (adjusted HR, 5.1; 95% CI, 1.4 18.7) and MRproANP levels with cardioembolic stroke (adjusted HR, 16.3; 95% CI, 3.7-70.9). CONCLUSIONS: Higher levels of PCT, a marker of infection, and MRproANP, a marker for hemodynamic stress, were independently associated with IS risk. PCT was specifically associated with small vessel and MRproANP with cardioembolic stroke risk. Further study is needed to validate these biomarkers and determine their significance in stroke risk prediction and prevention. PMID- 27197850 TI - Utility of Computed Tomographic Perfusion in Thrombolysis for Minor Stroke. AB - BACKGROUND AND PURPOSE: The use of thrombolysis in acute minor ischemic stroke (MIS) remains controversial. We sought to determine the safety and efficacy of intravenous tissue-type plasminogen activator (IV-tPA) in acute MIS patients with demonstrable penumbra on computed tomographic perfusion study. METHODS: Consecutive MIS patients with National Institutes of Health Stroke Scale <=3 were identified from a prospective single tertiary-center database over a 4.5-year period (2011-2015). Cases with demonstrable penumbra were analyzed according to treatment received: IV-tPA versus standard stroke-unit care without thrombolysis. RESULTS: Seventy-three patients of 195 acute MIS admissions had a demonstrable penumbra (34 IV-tPA versus 39 standard stroke-unit care). Overall median National Institutes of Health Stroke Scale and premorbid modified Rankin Scale were 2 and 0, respectively. Median age was 73.2 (interquartile range, 67.3-82.8) years. There were no differences in baseline demographics, risk factors, stroke localization and cause, rates of vascular occlusion (38.2% versus 38.5%; P=1.000), or mean penumbral volume (41.3 versus 25.1 mL; P=0.150; IV-tPA versus standard stroke-unit care) between groups. There were no symptomatic intracerebral hemorrhages in either group. Patients treated with IV-tPA were more likely to have an excellent functional outcome at discharge (88.2% versus 53.9%; P=0.002) and 90 days (91.2% versus 71.8%; P=0.042). Ordinal analysis demonstrated a favorable shift in modified Rankin Scale with IV-tPA both at discharge (odds ratio, 5.23; 95% confidence interval, 1.83-12.20) and 90 days (odds ratio, 4.35; 95% confidence interval, 1.77-11.36). CONCLUSIONS: In selected MIS patients with demonstrable penumbra on computed tomographic perfusion, IV-tPA is safe and associated with significant improvement in functional outcome at discharge and 90 days. PMID- 27197852 TI - Letter by Reddy et al Regarding Article, "Cannabis Use and Outcomes in Patients With Aneurysmal Subarachnoid Hemorrhage". PMID- 27197851 TI - Orolingual Angioedema During or After Thrombolysis for Cerebral Ischemia. AB - BACKGROUND AND PURPOSE: Orolingual angioedema (OLAE) is a life-threatening complication of intravenous thrombolysis. Our objective was to compare outcomes of patients with and without OLAE. METHODS: We prospectively included consecutive patients who received intravenous thrombolysis for cerebral ischemia at Lille University Hospital. We examined tongue and lips every 15 minutes during thrombolysis and <=30 minutes after. We evaluated the 3-month outcome with the modified Rankin scale (mRS) and compared outcomes of patients with and without OLAE. RESULTS: Of 923 consecutive patients, 20 (2.2%) developed OLAE. None of them needed oro-tracheal intubation. They were more likely to be under angiotensin-converting enzyme inhibitors (adjusted odds ratio [adjOR], 3.9; 95% confidence interval [CI], 1.6-9.7; P=0.005) to have total insular infarcts (OR, 5.0; 95% CI, 1.5-16.5; P=0.004) and tended to develop more symptomatic intracerebral hemorrhages. Results concerning angiotensin-converting enzyme inhibitors were not modified after adjustment for propensity scores (OR, 4.4; 95% CI, 1.6-11.9; P=0.004) or matched analysis based on propensity scores (OR, 3.4; 95% CI, 1.3-8.1; P=0.010). Patients with OLAE did not significantly differ at 3 months for the proportion of patients with mRS score of 0 to 1 (adjOR, 0.9; 95% CI, 0.3-2.1), mRS score of 0 to 2 (adjOR, 0.8; 95% CI, 0.1-1.8), and death (adjOR, 1.1; 95% CI, 0.3-3.8). CONCLUSIONS: OLAE occurs in 1 of 50 patients who receive intravenous thrombolysis, 1 of 10 in case of total insular infarct, and 1 of 6 if they are under angiotensin-converting enzyme inhibitors. Their long-term outcome does not differ from that of other patients. PMID- 27197853 TI - Reassessing the Stroke Belt: Using Small Area Spatial Statistics to Identify Clusters of High Stroke Mortality in the United States. AB - BACKGROUND AND PURPOSE: The stroke belt is described as an 8-state region with high stroke mortality across the southeastern United States. Using spatial statistics, we identified clusters of high stroke mortality (hot spots) and adjacent areas of low stroke mortality (cool spots) for US counties and evaluated for regional differences in county-level risk factors. METHODS: A cross-sectional study of stroke mortality was conducted using Multiple Cause of Death data (Centers for Disease Control and Prevention) to compute age-adjusted adult stroke mortality rates for US counties. Local indicators of spatial association statistics were used for hot-spot mapping. County-level variables were compared between hot and cool spots. RESULTS: Between 2008 and 2010, there were 393 121 stroke-related deaths. Median age-adjusted adult stroke mortality was 61.7 per 100 000 persons (interquartile range=51.4-74.7). We identified 705 hot-spot counties (22.4%) and 234 cool-spot counties (7.5%); 44.5% of hot-spot counties were located outside of the stroke belt. Hot spots had greater proportions of black residents, higher rates of unemployment, chronic disease, and healthcare utilization, and lower median income and educational attainment. CONCLUSIONS: Clusters of high stroke mortality exist beyond the 8-state stroke belt, and variation exists within the stroke belt. Reconsideration of the stroke belt definition and increased attention to local determinants of health underlying small area regional variability could inform targeted healthcare interventions. PMID- 27197854 TI - Thrombus Histology Suggests Cardioembolic Cause in Cryptogenic Stroke. AB - BACKGROUND AND PURPOSE: Ischemic stroke of undetermined cause is a major health issue because of its high frequency and clinical relevance. Histopathologic analysis of human thrombi, retrieved from stroke patients with large-vessel occlusion during mechanical thrombectomy, may provide information about underlying pathologies. This study examines the relationship between stroke causes and histological clot composition to identify specific patterns that might help to distinguish causes of cryptogenic stroke. METHODS: Thrombi of 145 consecutive stroke patients with large-vessel occlusion were collected during intracranial mechanical recanalization. The hematoxylin and eosin-stained specimens were quantitatively analyzed in terms of the relative fractions of the main constituents (red and white blood cells and fibrin/platelets). These data, along with additional clinical and interventional parameters, were compared for different stroke subtypes, as defined by the international Trial of Org 10172 in Acute Stroke Treatment criteria. RESULTS: The composition of thrombi from cardioembolic and noncardioembolic stroke patients differed significantly for all main thrombus components. Cardioembolic thrombi had higher proportions of fibrin/platelets (P=0.009), less erythrocytes (P=0.003), and more leucocytes (P=0.035) than noncardioembolic thrombi. Cryptogenic strokes showed strong overlap with cardioembolic strokes but not with noncardioembolic strokes, in terms of both thrombus histology and interventional and clinical outcome parameters. CONCLUSIONS: Quantitative evaluation of thrombus composition may help to distinguish between different stroke causes. Our findings support the notion that the majority of cryptogenic strokes are cardioembolic. PMID- 27197855 TI - Effects of hypervolemia by protein and glucose supplementation during aerobic training on thermal and arterial pressure regulations in hypertensive older men. AB - In Japan, the incidence of heat illness in older people has rapidly increased during midsummer in the last decade, and we suggested that whey protein+carbohydrate supplementation during aerobic training would increased plasma volume (PV) to enhance thermoregulatory adaptation in older men (J Appl Physiol 107: 725-733, 2009); however, >60% of people age 65 and older suffer from hypertension, and the symptoms may be worsened by hypervolemia. To examine this, we randomly divided 21 older men (~69 yr) with ~160 mmHg for systolic and ~90 mmHg for diastolic blood pressure at rest into two groups: Glc (n = 11) consuming glucose alone (25 g) and Pro-Glc (n = 10) consuming whey protein (10 g) + glucose (15 g), immediately after cycling exercise at 60-75% of peak aerobic capacity (Vo2 peak) for 60 min/day, 3 days/wk, for 8 wk. Before and after training, we measured PV (dye dilution), baroreflex sensitivity (BRS) of heart rate (Valsalva maneuver), and carotid arterial compliance (CAC) from carotid arterial diameter (ultrasound imaging) responses to pulsatile arterial pressure change (photoplethysmography) at rest. Additionally, we measured esophageal temperature (Tes) and forearm skin blood flow (plethysmography) during exercise at 60% pretraining Vo2 peak for 20 min in a warm environment. We found that the forearm skin vascular conductance response to increased Tes was enhanced in Pro-Glc with increased PV, but this was not found in Glc; however, despite the increased PV, arterial blood pressures rather decreased with increased CAC and BRS in Pro-Glc. Thus, the prescription was applicable to older men with hypertension to prevent heat illness during exercise. PMID- 27197858 TI - Invited Editorial on "Measurement of intraindividual airway tone heterogeneity and its importance in asthma": How does an airway and subsequently the lung become hyperresponsive? PMID- 27197856 TI - Age-induced oxidative stress: how does it influence skeletal muscle quantity and quality? AB - With advancing age, skeletal muscle function declines as a result of strength loss. These strength deficits are largely due to reductions in muscle size (i.e., quantity) and its intrinsic force-producing capacity (i.e., quality). Age-induced reductions in skeletal muscle quantity and quality can be the consequence of several factors, including accumulation of reactive oxygen and nitrogen species (ROS/RNS), also known as oxidative stress. Therefore, the purpose of this mini review is to highlight the published literature that has demonstrated links between aging, oxidative stress, and skeletal muscle quantity or quality. In particular, we focused on how oxidative stress has the potential to reduce muscle quantity by shifting protein balance in a deficit, and muscle quality by impairing activation at the neuromuscular junction, excitation-contraction (EC) coupling at the ryanodine receptor (RyR), and cross-bridge cycling within the myofibrillar apparatus. Of these, muscle weakness due to EC coupling failure mediated by RyR dysfunction via oxidation and/or nitrosylation appears to be the strongest candidate based on the publications reviewed. However, it is clear that age-associated oxidative stress has the ability to alter strength through several mechanisms and at various locations of the muscle fiber. PMID- 27197857 TI - Exercise-induced endothelial progenitor cell mobilization is attenuated in impaired glucose tolerance and type 2 diabetes. AB - Circulating endothelial progenitor cells (EPCs) contribute to vascular homeostasis and are fewer in those with type 2 diabetes mellitus (T2DM) compared with normal glucose tolerance (NGT), suggesting a link between EPCs and T2DM associated vasculopathies. The purpose of this study was to assess EPC number and mobilization by acute submaximal exercise in older adults with NGT, impaired glucose tolerance (IGT) or T2DM. We tested the hypothesis that EPC mobilization is lower in IGT compared with NGT and further reduced in older adults with T2DM. Forty-five older (50-75 yr of age) men and women with NGT (n = 18), IGT (n = 10), or T2DM (n = 17) were characterized and underwent submaximal aerobic exercise tests with blood sampling for enumeration of vascular endothelial growth factor receptor 2+ (VEGFR2+) cells, CD34+ hematopoetic progenitor cells, and CD34+/VEGFR2+ EPCs by flow cytometry before and after exercise. Basal EPC number was 65 and 61% lower in the IGT and T2DM groups, respectively, compared with the NGT group (P < 0.05). EPC number increased 23% after acute exercise in the NGT group (P < 0.01), but did not change in the IGT or T2DM groups. Before and after exercise, VEGFR2+ cell number was lower in a stepwise manner across the NGT, IGT, and T2DM groups (P < 0.05). Basal CD34+ cell number was lower in the IGT group compared with NGT (P < 0.05), but did not change after exercise in any group. These findings suggest a CD34+/VEGFR2+ EPC mobilization defect in IGT and T2DM that could play a role in the cardiovascular diseases and capillary rarefaction associated with insulin resistance. PMID- 27197859 TI - Alcohol breath test: gas exchange issues. AB - The alcohol breath test is reviewed with a focus on gas exchange factors affecting its accuracy. The basis of the alcohol breath test is the assumption that alveolar air reaches the mouth during exhalation with no change in alcohol concentration. Recent investigations have shown that alcohol concentration is altered during its transit to the mouth. The exhaled alcohol concentration is modified by interaction with the mucosa of the pulmonary airways. Exhaled alcohol concentration is not an accurate indicator of alveolar alcohol concentration. Measuring alcohol concentration in the breath is very different process than measuring a blood level from air equilibrated with a blood sample. Airway exchange of alcohol leads to a bias against certain individuals depending on the anatomic and physiologic characteristics. Methodological modifications are proposed to improve the accuracy of the alcohol breath test to become fair to all. PMID- 27197860 TI - Static and dynamic stress heterogeneity in a multiscale model of the asthmatic airway wall. AB - Airway hyperresponsiveness (AHR) is a key characteristic of asthma that remains poorly understood. Tidal breathing and deep inspiration ordinarily cause rapid relaxation of airway smooth muscle (ASM) (as demonstrated via application of length fluctuations to tissue strips) and are therefore implicated in modulation of AHR, but in some cases (such as application of transmural pressure oscillations to isolated intact airways) this mechanism fails. Here we use a multiscale biomechanical model for intact airways that incorporates strain stiffening due to collagen recruitment and dynamic force generation by ASM cells to show that the geometry of the airway, together with interplay between dynamic active and passive forces, gives rise to large stress and compliance heterogeneities across the airway wall that are absent in tissue strips. We show further that these stress heterogeneities result in auxotonic loading conditions that are currently not replicated in tissue-strip experiments; stresses in the strip are similar to hoop stress only at the outer airway wall and are under- or overestimates of stresses at the lumen. Taken together these results suggest that a previously underappreciated factor, stress heterogeneities within the airway wall and consequent ASM cellular response to this micromechanical environment, could contribute to AHR and should be explored further both theoretically and experimentally. PMID- 27197861 TI - Separate and combined effects of a 10-d exposure to hypoxia and inactivity on oxidative function in vivo and mitochondrial respiration ex vivo in humans. AB - An integrative evaluation of oxidative metabolism was carried out in 9 healthy young men (age, 24.1 +/- 1.7 yr mean +/- SD) before (CTRL) and after a 10-day horizontal bed rest carried out in normoxia (N-BR) or hypoxia (H-BR, FiO2 = 0.147). H-BR was designed to simulate planetary habitats. Pulmonary O2 uptake (Vo2) and vastus lateralis fractional O2 extraction (changes in deoxygenated hemoglobin+myoglobin concentration, Delta[deoxy(Hb+Mb)] evaluated using near infrared spectroscopy) were evaluated in normoxia and during an incremental cycle ergometer (CE) and one-leg knee extension (KE) exercise (aimed at reducing cardiovascular constraints to oxidative function). Mitochondrial respiration was evaluated ex vivo by high-resolution respirometry in permeabilized vastus lateralis fibers. During CE Vo2peak and Delta[deoxy(Hb+Mb)]peak were lower (P < 0.05) after both N-BR and H-BR than during CTRL; during KE the variables were lower after N-BR but not after H-BR. During CE the overshoot of Delta[deoxy(Hb+Mb)] during constant work rate exercise was greater in N-BR and H BR than CTRL, whereas during KE a significant difference vs. CTRL was observed only after N-BR. Maximal mitochondrial respiration determined ex vivo was not affected by either intervention. In N-BR, a significant impairment of oxidative metabolism occurred downstream of central cardiovascular O2 delivery and upstream of mitochondrial function, possibly at the level of the intramuscular matching between O2 supply and utilization and peripheral O2 diffusion. Superposition of hypoxia on bed rest did not aggravate, and partially reversed, the impairment of muscle oxidative function in vivo induced by bed rest. The effects of longer exposures will have to be determined. PMID- 27197862 TI - Role of histidyl dipeptides in contractile function of fast and slow motor units in rat skeletal muscle. AB - The physiological role of the muscle histidyl dipeptides carnosine and anserine in contractile function of various types of muscle fibers in vivo is poorly understood. Ten adult male Wistar rats were randomly assigned to two groups: control and supplemented for 10 wk with beta-alanine, the precursor of carnosine (~640 mg.kg body wt(-1).day(-1)). Thereafter, contractile properties and fatigability of isolated fast fatigable (FF), fast resistant to fatigue (FR), and slow motor units (MUs) from the medial gastrocnemius were determined in deeply anaesthetized animals. The fatigue resistance was tested with a 40-Hz fatigue protocol followed by a second protocol at 40 Hz in fast and 20 Hz in slow units. In the supplemented rats, histidyl dipeptide concentrations significantly increased (P < 0.05) by 25% in the red portion of the gastrocnemius, and carnosine increased by 94% in the white portion. The twitch force of FF units and maximum tetanic force of FR units were significantly increased (P < 0.05), and the half-relaxation time was prolonged in slow units (P < 0.05). FF units showed less fatigue during the first 10 s, and FR units showed higher forces between 10 and 60 s during the 40-Hz fatigue test. In slow units, forces declined less during the first 60 s of the 20-Hz test. In conclusion, this in vivo experiment demonstrates that an elevation in muscle histidyl dipeptide content elicits beneficial changes in MU contractile characteristics and fatigue resistance. Carnosine and anserine seem to play an important yet divergent role in various MUs. PMID- 27197864 TI - Withdrawal of ventilation at the request of a patient with motor neurone disease: guidance for professionals. PMID- 27197866 TI - Patients need action, not words, on UK end-of-life care. PMID- 27197867 TI - Dying Speech of an Old Philosopher. PMID- 27197869 TI - Comment on 'Evaluation of choroidal thickness in patients with scleroderma'. PMID- 27197868 TI - Determinants of visual acuity outcomes in eyes with neovascular AMD treated with anti-VEGF agents: an instrumental variable analysis of the AURA study. AB - PurposeTo identify the strongest variable(s) linked with the number of ranibizumab injections and outcomes in AURA, and to identify ways to improve outcomes using this association.MethodsAURA was a large observational study that monitored visual acuity over a 2-year period in patients with neovascular age related macular degeneration (AMD) who received ranibizumab injections. Baseline characteristics, resource use, and outcomes were analyzed using an instrumental variable approach and regression analysis.ResultsData were analyzed from 2227 patients enrolled in AURA. Optical coherence tomography (OCT) and ophthalmoscopy were the most common diagnostic tests used, and this combination was the strongest instrumental variable. Use of OCT and ophthalmoscopy affected the number of injections given and resulted in an increase in visual acuity gains from baseline of 17.6 letters in year 1 and 2.5 letters in year 2. Regression models using the instrumental variable (OCT and ophthalmoscopy combined) showed that >=5.1 (95% CI: 3.3-11.4) ranibizumab injections were needed to maintain visual acuity from baseline to year 1 and >=8.3 (95% CI: 5.3-18.8) injections were needed to maintain visual acuity from year 1 to year 2. To gain >=15 letters, >=7.9 (95% CI: 5.1-17.5) ranibizumab injections would be needed in year 1 and >=16.1 (95% CI: 10.3-36.4) injections would be needed over 2 years.ConclusionsThese findings highlight the role that regular monitoring plays in guiding neovascular AMD therapy and they showed that the number of ranibizumab injections needed to maintain visual acuity is higher than that administered in AURA. PMID- 27197870 TI - Variability of disease activity in patients treated with ranibizumab for neovascular age-related macular degeneration. AB - PurposeTo analyze choroidal neovasularization (CNV) activity and recurrence patterns in patients with neovascular age-related macular degeneration (nAMD) treated with ranibizumab, and the correlation with individual intraocular vascular endothelial growth factor (VEGF) suppression time (VST).MethodsPost-hoc analysis of data from a prospective, non-randomized clinical study. Patients with nAMD treated with ranibizumab on a pro re nata regimen. Disease activity was analyzed monthly by spectral-domain optical coherence tomography and correlated with VSTs.ResultsOverall, 73 eyes of 73 patients were included in the study with a mean follow-up of 717 days (range: 412-1239 days). Overall, the mean CNV activity-free interval was 76.5 days (range: 0-829 days). The individual range of the length of dry intervals was high. A total of 42% of patients had a range of more than 90 days. Overall, 16% of patients showed persistent activity. And 12% stayed dry after the initial ranibizumab treatment. No significant correlation was found between the CNV-recurrence pattern and VST (P=0.12).ConclusionsCNV activity in nAMD is irregular, which is reflected in the range of the duration of dry intervals and late recurrences. The biomarker VST solely seems not to be sufficient to explain recurrence pattern of CNV in all AMD patients. PMID- 27197871 TI - Comparison of botulinum toxin-A injection in lacrimal gland and conjunctivodacryocystorhinostomy for treatment of epiphora due to proximal lacrimal system obstruction. AB - PurposeTo investigate and compare the efficacy of botulinum toxin-A injection in the lacrimal gland and conjunctivodacryocystorhinostomy surgery for the treatment of epiphora caused by proximal lacrimal system obstruction.MethodsCharts of the patients with proximal canalicular obstruction who had undergone conjunctivodacryocystorhinostomy with permanent tube insertion (18 patients, group 1) or 4 units of botulinum toxin-A injection in the palpebral lobe of the lacrimal gland (20 patients, group 2) were reviewed retrospectively. The upper lacrimal system obstruction was diagnosed by lacrimal system irrigation. Schirmer 1 test and Munk epiphora grading for evaluation of epiphora were performed before the interventions and on tenth day, first, third, and sixth months after the interventions.ResultsImprovement of epiphora was statistically significant at all visits when compared with values before injection (P<0.001) in both of groups. When two techniques were compared, difference in degree of epiphora before and after intervention was not statistically significant (P<0.05). In group 2, none of the patients had punctate epitheliopathy, although there was a significant decrease in Schirmer test results (P<0.001, paired t-test). In group 1, 9 cases (50%) had tube dislocation, 4 cases (22.2%) had obstruction, and granuloma formation. Five cases (25%) had ptosis in group 2.Conclusion Conjunctivodacryocystorhinostomy requires surgical experience, special postoperative care, and multiple revisions. As botulinum toxin-A injection in the lacrimal gland is technically easy, less-invasive, safe, with reversible effects, it can be considered as an alternative treatment in patients with proximal lacrimal system obstruction. PMID- 27197873 TI - Halogenated earth abundant metalloporphyrins as photostable sensitizers for visible-light-driven water oxidation in a neutral phosphate buffer solution. AB - Very photostable tetrachloro-metalloporphyrins were developed as sensitizers for visible-light-driven water oxidation coupled to cobalt based water-oxidation catalysts in concentrated (0.1 M) phosphate buffer solution. Potassium persulfate (K2S2O8) acts as a sacrificial electron acceptor to oxidize the metalloporphyrin photosensitizers in their excited states. The radical cations thus produced drive the cobalt based water-oxidation catalysts: Co4O4-cubane and Co(NO3)2 as pre catalyst for cobalt-oxide (CoOx) nanoparticles. Two different metalloporphyrins (Cu(ii) and Ni(ii)) both showed very high photostability in the photocatalytic reaction, as compared to non-halogenated analogues. This indicates that photostability primarily depends on the substitution of the porphyrin macrocycle, not on the central metal. Furthermore, our molecular design strategy not only positively increases the electrochemical potential by 120-140 mV but also extends the absorption spectrum up to ~600 nm. As a result, the solar photon capturing abilities of halogenated metalloporphyrins (Cu(ii) and Ni(ii)) are comparable to that of the natural photosynthetic pigment, chlorophyll a. We successfully demonstrate long-term (>3 h) visible-light-driven water oxidation using our molecular system based on earth-abundant (first-row transition) metals in concentrated phosphate buffer solution. PMID- 27197872 TI - Curcumin: A multi-target disease-modifying agent for late-stage transthyretin amyloidosis. AB - Transthyretin amyloidoses encompass a variety of acquired and hereditary diseases triggered by systemic extracellular accumulation of toxic transthyretin aggregates and fibrils, particularly in the peripheral nervous system. Since transthyretin amyloidoses are typically complex progressive disorders, therapeutic approaches aiming multiple molecular targets simultaneously, might improve therapy efficacy and treatment outcome. In this study, we evaluate the protective effect of physiologically achievable doses of curcumin on the cytotoxicity induced by transthyretin oligomers in vitro by showing reduction of caspase-3 activity and the levels of endoplasmic reticulum-resident chaperone binding immunoglobulin protein. When given to an aged Familial Amyloidotic Polyneuropathy mouse model, curcumin not only reduced transthyretin aggregates deposition and toxicity in both gastrointestinal tract and dorsal root ganglia but also remodeled congophilic amyloid material in tissues. In addition, curcumin enhanced internalization, intracellular transport and degradation of transthyretin oligomers by primary macrophages from aged Familial Amyloidotic Polyneuropathy transgenic mice, suggesting an impaired activation of naive phagocytic cells exposed to transthyretin toxic intermediate species. Overall, our results clearly support curcumin or optimized derivatives as promising multi target disease-modifying agent for late-stage transthyretin amyloidosis. PMID- 27197875 TI - Synthesis of the derivatives of 6-amino-uracil labelled with 14 C. AB - The radioactively labelled 6-amino-5-nitroso-uracil (1) and 5-acetyl-6-amino-1,3 dimethyl-uracil (2) were required for metabolic studies to assess their suitability as drug candidates. A common precursor for both compounds was [cyano 14 C]cyanoacetic acid (6), readily prepared from potassium [14 C]cyanide. ACS reagents, namely, diethyl ether, acetic acid and acetic anhydride, had to be rigorously repurified to achieve a successful synthesis of 14 C-labelled compounds on a tenth-of-a-milligramme scale. 6-Amino-5-nitroso-[6-14 C]uracil (1 14 C) (0.55 mCi) was prepared with radiochemical purity > 98% and specific activity (SA) = 55.6 mCi/mmol. 5-Acetyl-6-amino-1,3-dimethyl-[6-14 C]uracil (2-14 C) (8 mCi) was prepared with radiochemical purity > 97% and SA = 55.6 mCi/mmol. It has been shown that a SA assay can be made from standard 13 C NMR spectra, thus avoiding the need to perform lengthier inverse-gated 13 C NMR experiments. PMID- 27197874 TI - Distinctive features of single nucleotide alterations in induced pluripotent stem cells with different types of DNA repair deficiency disorders. AB - Disease-specific induced pluripotent stem cells (iPSCs) have been used as a model to analyze pathogenesis of disease. In this study, we generated iPSCs derived from a fibroblastic cell line of xeroderma pigmentosum (XP) group A (XPA-iPSCs), a rare autosomal recessive hereditary disease in which patients develop skin cancer in the areas of skin exposed to sunlight. XPA-iPSCs exhibited hypersensitivity to ultraviolet exposure and accumulation of single-nucleotide substitutions when compared with ataxia telangiectasia-derived iPSCs that were established in a previous study. However, XPA-iPSCs did not show any chromosomal instability in vitro, i.e. intact chromosomes were maintained. The results were mutually compensating for examining two major sources of mutations, nucleotide excision repair deficiency and double-strand break repair deficiency. Like XP patients, XPA-iPSCs accumulated single-nucleotide substitutions that are associated with malignant melanoma, a manifestation of XP. These results indicate that XPA-iPSCs may serve a monitoring tool (analogous to the Ames test but using mammalian cells) to measure single-nucleotide alterations, and may be a good model to clarify pathogenesis of XP. In addition, XPA-iPSCs may allow us to facilitate development of drugs that delay genetic alteration and decrease hypersensitivity to ultraviolet for therapeutic applications. PMID- 27197877 TI - Probing topological protection using a designer surface plasmon structure. AB - Topological photonic states, inspired by robust chiral edge states in topological insulators, have recently been demonstrated in a few photonic systems, including an array of coupled on-chip ring resonators at communication wavelengths. However, the intrinsic difference between electrons and photons determines that the 'topological protection' in time-reversal-invariant photonic systems does not share the same robustness as its counterpart in electronic topological insulators. Here in a designer surface plasmon platform consisting of tunable metallic sub-wavelength structures, we construct photonic topological edge states and probe their robustness against a variety of defect classes, including some common time-reversal-invariant photonic defects that can break the topological protection, but do not exist in electronic topological insulators. This is also an experimental realization of anomalous Floquet topological edge states, whose topological phase cannot be predicted by the usual Chern number topological invariants. PMID- 27197879 TI - A dual-channel detection of mercuric ions using a label free G-quadruplex-based DNAzyme molecule. AB - We have constructed a 'turn-off' and label free bio-sensor using a DNAzyme molecule. This facile bio-sensor is capable of selective detection of mercuric ions with a high sensitivity and satisfactory dynamic range. More importantly, it is able to generate both fluorescent and colourimetric signals for detection. This dual-channel bio-sensor is expected to afford high detection confidence and overcome false-positive readout especially when assaying complex biological samples. PMID- 27197876 TI - The German ROP Registry: data from 90 infants treated for retinopathy of prematurity. AB - PURPOSE: The German retinopathy of prematurity (ROP) Registry collects data on treated ROP in a multicentre approach to analyse epidemiology and treatment patterns of severe ROP. METHODS: Nine centres entered data from 90 treated ROP infants (born between January 2011 and December 2013) into a central database. Analysis included incidence rate of severe ROP, demographic data, stage of ROP, treatment patterns, recurrence rates, relevant comorbidities and ophthalmological or systemic complications associated with treatment. RESULTS: Treatment rate for ROP was 3.2% of the screened population. The most frequent ROP stage at time of treatment was zone II, stage 3 + (137 eyes). Treatment was bilateral in 97% of infants. Treatment patterns changed over time from 7% anti-vascular endothelial growth factor (VEGF) monotherapy in 2011 to 32% in 2014. Overall, laser treatment was the predominant treatment. However, all infants with zone I disease received anti-VEGF treatment. About 19% of infants required retreatment (16% of laser treated and 21% of anti-VEGF treated infants). Mean time between first and second treatment was 3.8 weeks (+/- 11 days) for laser-treated and 10.4 weeks (+/- 60 days) for anti-VEGF-treated infants. CONCLUSION: This study is the first multicentre analysis of severe ROP in Germany. The identified treatment patterns find laser as the most prevalent form of therapy, with an increasing use of anti VEGF therapy over recent years. Recurrence rates were relatively high overall with slightly higher recurrence rates and later recurrence times in the anti-VEGF group. Anti-VEGF was predominantly used for high-risk stages like AP-ROP and zone I disease. PMID- 27197878 TI - Graphene Oxide promotes embryonic stem cell differentiation to haematopoietic lineage. AB - Pluripotent stem cells represent a promising source of differentiated tissue specific stem and multipotent progenitor cells for regenerative medicine and drug testing. The realisation of this potential relies on the establishment of robust and reproducible protocols of differentiation. Several reports have highlighted the importance of biomaterials in assisting directed differentiation. Graphene oxide (GO) is a novel material that has attracted increasing interest in the field of biomedicine. In this study, we demonstrate that GO coated substrates significantly enhance the differentiation of mouse embryonic stem (ES) cells to both primitive and definitive haematopoietic cells. GO does not affect cell proliferation or survival of differentiated cells but rather enhances the transition of haemangioblasts to haemogenic endothelial cells, a key step during haematopoietic specification. Importantly, GO also improves, in addition to murine, human ES cell differentiation to blood cells. Taken together, our study reveals a positive role for GO in haematopoietic differentiation and suggests that further functionalization of GO could represent a valid strategy for the generation of large numbers of functional blood cells. Producing these cells would accelerate haematopoietic drug toxicity testing and treatment of patients with blood disorders or malignancies. PMID- 27197881 TI - [Delusion versus delirium]. PMID- 27197882 TI - [Role of serum leptin in the severity of coronary artery disease in patients with stable angina]. AB - BACKGROUND AND OBJECTIVES: Leptin is a plasmatic peptide hormone that has been related to cardiovascular homeostasis and atherosclerosis but much is still unknown about its relationship with coronary artery disease. The aim of this study was to evaluate the value of serum leptin in patients with stable angina and its relationship with the severity of coronary disease. PATIENTS AND METHODS: 204 patients, 152 with stable angina (coronary artery disease group) and 52 without coronary disease excluded by cardiac computerized tomography (control group) were included. The coronary artery disease group was divided into 2 subgroups according to severity of coronary disease (single or multivessel disease, 46 and 106 patients, respectively). Serum leptin levels were determined by Enzyme-Linked InmunoSorbent Assay. RESULTS: Leptin levels were significantly higher in patients with multivessel disease and were independently associated with a greater severity of coronary artery disease when compared with controls (OR 1.14; 95%CI: 1.03-1.27; p=0.014) and with patients with single vessel disease (OR 1.12; 95%CI: 1.01-1.25; p=0.036). Serum leptin was tested as a diagnostic marker of multivessel disease with an area under the curve obtained from Receiver Operating Characteristics of 0.6764 (95%CI 0.5765-0.7657). CONCLUSIONS: Serum leptin levels were associated in patients with stable angina with the severity of coronary artery disease, suggesting its value in the development of coronary disease and as a future therapeutic target. PMID- 27197883 TI - [Erythema nodosum]. PMID- 27197884 TI - [SAPHO syndrome in patients undergoing bariatric surgery: Causality or coincidence?]. PMID- 27197880 TI - Precision Oncology Medicine: The Clinical Relevance of Patient-Specific Biomarkers Used to Optimize Cancer Treatment. AB - Precision medicine in oncology is the result of an increasing awareness of patient-specific clinical features coupled with the development of genomic-based diagnostics and targeted therapeutics. Companion diagnostics designed for specific drug-target pairs were the first to widely utilize clinically applicable tumor biomarkers (eg, HER2, EGFR), directing treatment for patients whose tumors exhibit a mutation susceptible to an FDA-approved targeted therapy (eg, trastuzumab, erlotinib). Clinically relevant germline mutations in drug metabolizing enzymes and transporters (eg, TPMT, DPYD) have been shown to impact drug response, providing a rationale for individualized dosing to optimize treatment. The use of multigene expression-based assays to analyze an array of prognostic biomarkers has been shown to help direct treatment decisions, especially in breast cancer (eg, Oncotype DX). More recently, the use of next generation sequencing to detect many potential "actionable" cancer molecular alterations is further shifting the 1 gene-1 drug paradigm toward a more comprehensive, multigene approach. Currently, many clinical trials (eg, NCI MATCH, NCI-MPACT) are assessing novel diagnostic tools with a combination of different targeted therapeutics while also examining tumor biomarkers that were previously unexplored in a variety of cancer histologies. Results from ongoing trials such as the NCI-MATCH will help determine the clinical utility and future development of the precision-medicine approach. PMID- 27197885 TI - [Dyslipidaemia and atherogenic risk in patients with systemic lupus erythematosus]. AB - INTRODUCTION: Dyslipidaemia is a common comorbidity in patients with systemic lupus erythematosus. PATIENTS AND METHODS: Fifty-one patients were included. Variables associated with the disease and the drugs used were recorded. Atherogenic risk was calculated. Chi square was used for categorical variables. ANOVA was performed and a logistic regression model to determine the association of the variables with the presence of dyslipidaemia. RESULTS: A percentage of 68.6 had dyslipidaemia. A significant difference between the presence of dyslipidaemia and activity index measured by SLEDAI was found, the presence of lupus nephritis, use of prednisone>=20mg/day, evolution of the disease<3 years. Significance between the absence of dyslipidaemia and use of hydroxychloroquine was found. SLEDAI>=4 and the use of prednisone>=20mg/day were independently associated with the presence of dyslipidaemia. The average of Castelli rate was 5.02, the Kannel index was 2.97 and triglyceride/HDL-C ratio was 5.24. CONCLUSIONS: Patients with systemic lupus erythematosus have a high prevalence of dyslipidaemia and a high atherogenic rate, which increases cardiovascular risk significantly. PMID- 27197887 TI - Homogeneous rhodium(i)-catalysis in de novo heterocycle syntheses. AB - Recent research has led to the development of mild, efficient and selective catalytic systems based on Rh(i) complexes. This review summarises the applications of these catalysts to the synthesis of heterocycles from simple building blocks. Included herein are approaches based on cycloisomerisation, cycloaddition, hydroacylation and hydroarylation reactions, as well as various tandem and domino procedures and carbonylation processes. PMID- 27197886 TI - Compression loading-induced stress responses in intervertebral disc cells encapsulated in 3D collagen constructs. AB - Cells protect themselves from stresses through a cellular stress response. In the interverebral disc, such response was also demonstrated to be induced by various environmental stresses. However, whether compression loading will cause cellular stress response in the nucleus pulposus cells (NPCs) is not well studied. By using an in vitro collagen microencapsulation model, we investigated the effect of compression loading on the stress response of NPCs. Cell viability tests, and gene and protein expression experiments were conducted, with primers for the heat shock response (HSR: HSP70, HSF1, HSP27 and HSP90), and unfolded protein response (UPR: GRP78, GRP94, ATF4 and CHOP) genes and an antibody to HSP72. Different gene expression patterns occurred due to loading type throughout experiments. Increasing the loading strain for a short duration did not increase the stress response genes significantly, but over longer durations, HSP70 and HSP27 were upregulated. Longer loading durations also resulted in a continuous upregulation of HSR genes and downregulation of UPR genes, even after load removal. The rate of apoptosis did not increase significantly after loading, suggesting that stress response genes might play a role in cell survival following mechanical stress. These results demonstrate how mechanical stress might induce and control the expression of HSR and UPR genes in NPCs. PMID- 27197888 TI - Disproportionate trends in ulnar collateral ligament reconstruction: projections through 2025 and a literature review. AB - BACKGROUND: Medial ulnar collateral ligament (UCL) injuries of the elbow that require surgical management are uncommon. There is growing evidence, however, suggesting that the incidence of UCL reconstruction (UCLR) procedures is rapidly increasing. We sought to quantify the incidence of age-related trends for UCLR from 2003 to 2014 and subsequently to project future trends through 2025. We hypothesized that as the total number of UCLRs performed increased, a disproportionate incidence among younger patients would be observed. METHODS: New York State's Statewide Planning and Research Cooperative System database was queried from 2003 to 2014 to identify individuals between 10 and 40 years old undergoing UCLR. Poisson regression was used to develop future projections for UCLR and New York State population through 2025, and incidence estimates per 100,000 people were calculated. RESULTS: In New York State between 2003 and 2014, there were 890 patients who underwent UCLR, with average annual incidence per 100,000 people equaling 6.3 +/- 2.8 for ages 15 to 19 years, significantly greater than for all other age groups (P < .001). Projections from 2015 through 2025 suggest that incidence in 15- to 19-year-olds and 20- to 24-year-olds will continue to rapidly increase while rates for other age groups will remain relatively stable. CONCLUSIONS: The number of UCLRs performed between 2003 and 2014 increased by 343%, and a disproportionate trend in average annual incidence for patients between 15 and 19 years old was observed. As our review of the literature questioned outcomes in adolescent athletes after UCLR, continued attempts at preventing these injuries in the young throwing athlete remain paramount. PMID- 27197890 TI - Corrigendum: First evidence of European eels exiting the Mediterranean Sea during their spawning migration. PMID- 27197889 TI - Dietary selenium intake and mortality in two population-based cohort studies of 133 957 Chinese men and women. AB - OBJECTIVE: To investigate the potential influence of dietary Se intake on mortality among Chinese populations. DESIGN: We prospectively evaluated all cause, CVD and cancer mortality risks associated with dietary Se intake in participants of the Shanghai Women's Health Study (SWHS) and the Shanghai Men's Health study (SMHS). Dietary Se intake was assessed by validated FFQ during in person interviews. Cox proportional hazards models were used to calculate hazard ratios (HR) and 95 % CI. SETTING: Urban city in China. SUBJECTS: Chinese adults (n 133 957). RESULTS: During an average follow-up of 13.90 years in the SWHS and 8.37 years in the SMHS, 5749 women and 4217 men died. The mean estimated dietary Se intake was 45.48 MUg/d for women and 51.34 MUg/d for men, respectively. Dietary Se intake was inversely associated with all-cause mortality and CVD mortality in both women and men, with respective HR for the highest compared with the lowest quintile being 0.79 (95 % CI 0.71, 0.88; P trend<0.0001) and 0.80 (95 % CI 0.66, 0.98; P trend=0.0268) for women, and 0.79 (95 % CI 0.70, 0.89; P trend=0.0001) and 0.66 (95 % CI 0.54, 0.82; P trend=0.0002) for men. No significant associations were observed for cancer mortality in both women and men. Results were similar in subgroup and sensitivity analyses. CONCLUSIONS: Dietary Se intake was inversely associated with all-cause and cardiovascular mortality in both sexes, but not cancer mortality. PMID- 27197892 TI - A retrospective audit of referral letter quality from general practice to an inner-city emergency department. AB - OBJECTIVES: Our primary aim was to analyse the quality of letters from general practitioners (GPs) to the ED as defined by two checklists: the authors' own nine item list and a template published in 2013 by the New South Wales Agency for Clinical Innovation. The secondary aim was to determine if referral quality was influenced by letter format (handwritten or computer-generated) or urgency of the patient's condition (defined by triage category). METHODS: The present study is a retrospective audit of records of patients presenting to Royal Prince Alfred Hospital ED from a GP during February and March 2014. RESULTS: Out of 12 199 ED presentations, 575 (4.7%) were recommended by a GP and 414 (72.0%) had a letter. Greater than 60% completion was achieved in 80.9% of letters compared to our own checklist, and in 6.3% compared to the Agency for Clinical Innovation checklist. Computer-generated letters were more likely to be fully legible and include an accurate medical history and medication list. Handwritten letters were less frequent (11.9%) but of poorer quality and legibility. Overall, less than half of letters contained results, psychosocial history or vaccination history. Referrals for patients assigned an urgent triage category were more likely to contain examination findings, but there was otherwise no difference in quality. CONCLUSIONS: Referral quality was influenced by letter format but not by urgency of the patient's condition. Omission of information from referral letters potentially risks patient safety. Handwritten referrals should be abandoned. Comprehensive electronic letter templates and regular updating of medications, comorbidities and allergies are encouraged. PMID- 27197891 TI - An Atypical System for Studying Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma. AB - Intrahepatic and extrahepatic metastases are frequently detected in hepatocellular carcinoma (HCC). Epithelial-mesenchymal transition (EMT) is believed to drive metastasis. There are not many well-established model systems to study EMT in HCC. Here we identified an atypical EMT while characterizing a population of mesenchymal cells in Huh7.5 hepatoma cell cultures. Cells with distinct morphology appeared during geneticin treatment of Huh7.5 cultures. Molecular characterization of geneticin resistant Huh7.5M cells confirmed EMT. Huh7.5M cells expressed cancer stem cell markers. p38MAPK and ERK1/2 were substantially activated in Huh7.5M cells. Their Inhibition elevated E-Cadherin expression with concerted suppression of Vimentin and anchorage independent growth in Huh7.5M cells. TGFbeta could not induce EMT in Huh7.5 cultures, but enriched mesenchymal populations, similar to geneticin. Huh7.5M cells formed more aggressive solid tumors, primarily comprising cells with epithelial morphology, in nude mice. Canonical EMT-TFs did not participate in this atypical EMT, indicating that the established canonical EMT-TFs do not drive every EMT and there is a dire need to identify additional factors. The system that we characterized is a unique model to study EMT, MET and biphasic TGFbeta signaling in HCC and offers considerable potential to facilitate more insightful studies on deeper questions in tumor metastasis. PMID- 27197893 TI - Dissemination of original NMR data enhances reproducibility and integrity in chemical research. AB - The notion of data transparency is gaining a strong awareness among the scientific community. The availability of raw data is actually regarded as a fundamental way to advance science by promoting both integrity and reproducibility of research outcomes. Particularly, in the field of natural product and chemical research, NMR spectroscopy is a fundamental tool for structural elucidation and quantification (qNMR). As such, the accessibility of original NMR data, i.e., Free Induction Decays (FIDs), fosters transparency in chemical research and optimizes both peer review and reproducibility of reports by offering the fundamental tools to perform efficient structural verification. Although original NMR data are known to contain a wealth of information, they are rarely accessible along with published data. This viewpoint discusses the relevance of the availability of original NMR data as part of good research practices not only to promote structural correctness, but also to enhance traceability and reproducibility of both chemical and biological results. PMID- 27197895 TI - Increasing Access. PMID- 27197900 TI - Erratum. PMID- 27197894 TI - The association between religion/spirituality and mental health in cancer. PMID- 27197901 TI - Sequential fetal serum beta2-microglobulin to predict postnatal renal function in bilateral or low urinary tract obstruction. AB - OBJECTIVE: Fetal serum beta2-microglobulin has been shown to predict postnatal renal outcome in cases of fetal obstructive uropathy. We assessed the value of serial measurements of fetal serum beta2-microglobulin in the prediction of postnatal renal outcome. METHODS: We retrospectively studied renal outcome in 42 fetuses with bilateral or low urinary tract obstruction that had fetal blood sampling on at least two occasions to assay serum levels of beta2-microglobulin. Amniotic fluid volume at the time of each sampling was recorded. We classified renal outcome as either favorable (when postnatal renal function was normal) or adverse (when postnatal chronic renal failure occurred or when renal dysplasia at autopsy was noted). A beta2-microglobulin cut-off of 5 mg/L and amniotic fluid index of 5 cm were used to predict postnatal renal outcome. RESULTS: Renal outcome was adverse in 28 cases and favorable in 14. In 12 (28.6%) cases, fetal serum beta2-microglobulin concentration differed between the first and last measurement. Prediction of postnatal renal outcome was correct in 11 of these cases based on the last beta2-microglobulin measurement. The sensitivity of beta2 microglobulin in predicting renal outcome was significantly higher (P = 0.005) when using the last rather than the first measurement (96.4% vs 64.3%), with similar specificity for both measurements (85.7% vs 78.6%, non-significant). The sensitivity of amniotic fluid volume was also significantly higher (P = 0.005) when using the last rather than the first measurement (75.0% vs 35.7%), with similar specificity for both measurements (64.3% vs 71.4%, non-significant). CONCLUSION: Sequential measurement of serum beta2-microglobulin, performed for adverse ultrasound findings, such as renal parenchymal abnormality or decreasing amniotic fluid volume, predicts postnatal renal outcome more accurately than does a single assay. This may be due to possible worsening of renal injury with increasing duration of urinary tract obstruction. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 27197902 TI - Membrane damage as first and DNA as the secondary target for anti-candidal activity of antimicrobial peptide P7 derived from cell-penetrating peptide ppTG20 against Candida albicans. AB - P7, a peptide analogue derived from cell-penetrating peptide ppTG20, possesses antibacterial and antitumor activities without significant hemolytic activity. In this study, we investigated the antifungal effect of P7 and its anti-Candida acting mode in Candida albicans. P7 displayed antifungal activity against the reference C. albicans (MIC = 4 MUM), Aspergilla niger (MIC = 32 MUM), Aspergillus flavus (MIC = 8 MUM), and Trichopyton rubrum (MIC = 16 MUM). The effect of P7 on the C. albicans cell membrane was examined by investigating the calcein leakage from fungal membrane models made of egg yolk l-phosphatidylcholine/ergosterol (10 : 1, w/w) liposomes. P7 showed potent leakage effects against fungal liposomes similar to Melittin-treated cells. C. albicans protoplast regeneration assay demonstrated that P7 interacted with the C. albicans plasma membrane. Flow cytometry of the plasma membrane potential and integrity of C. albicans showed that P7 caused 60.9 +/- 1.8% depolarization of the membrane potential of intact C. albicans cells and caused 58.1 +/- 3.2% C. albicans cell membrane damage. Confocal laser scanning microscopy demonstrated that part of FITC-P7 accumulated in the cytoplasm. DNA retardation analysis was also performed, which showed that P7 interacted with C. albicans genomic DNA after penetrating the cell membrane, completely inhibiting the migration of genomic DNA above the weight ratio (peptide : DNA) of 6. Our results indicated that the plasma membrane was the primary target, and DNA was the secondary intracellular target of the mode of action of P7 against C. albicans. Copyright (c) 2016 European Peptide Society and John Wiley & Sons, Ltd. PMID- 27197903 TI - Auditory top-down control and affective theory of mind in schizophrenia with and without hallucinations. AB - Social cognitive impairments may represent a core feature of schizophrenia and above all are a strong predictor of positive psychotic symptoms. Previous studies could show that reduced inhibitory top-down control contributes to deficits in theory of mind abilities and is involved in the genesis of hallucinations. The current study aimed to investigate the relationship between auditory inhibition, affective theory of mind and the experience of hallucinations in patients with schizophrenia. In the present study, 20 in-patients with schizophrenia and 20 healthy controls completed a social cognition task (the Reading the Mind in the Eyes Test) and an inhibitory top-down Dichotic Listening Test. Schizophrenia patients with greater severity of hallucinations showed impaired affective theory of mind as well as impaired inhibitory top-down control. More dysfunctional top down inhibition was associated with poorer affective theory of mind performance, and seemed to mediate the association between impairment to affective theory of mind and severity of hallucinations. The findings support the idea of impaired theory of mind as a trait marker of schizophrenia. In addition, dysfunctional top down inhibition may give rise to hallucinations and may further impair affective theory of mind skills in schizophrenia. PMID- 27197904 TI - Cognitive functioning in individuals at ultra-high risk for psychosis, first degree relatives of patients with psychosis and patients with first-episode schizophrenia. AB - OBJECTIVE: The aim of the present study was to investigate and compare cognitive functioning of first-degree relatives of people with schizophrenia who were also at ultra-high risk (UHR) for psychosis with patients with first-episode (FE) schizophrenia, first degree relatives of patients not fulfilling UHR criteria (FDR), and healthy control (HC) subjects. METHOD: Forty subjects in each group were included, underwent a face-to-face interview and completed a neurocognitive test battery, including the Trail Making Test-A (TMT-A, psychomotor functions), Stroop Color Word Test (attention), Digit Symbol Coding Test (DST, processing speed and working memory) and Hopkins Verbal Leaning Test-Revised (HVLT-R, verbal memory). RESULTS: Functioning in all the cognitive test domains displayed a gradual decrease from the HC, FDR, UHR to FE groups. After controlling for covariates, there were still significant differences in TMT-A (F(7160)=35.4, P<0.001), DST (F(7160)=38.9, P<0.001), Stroop Color Word Test (F(7160)=35.0, P<0.001), Stroop Word Test (F(7160)=36.2, P<0.001), Stroop Color Test (F(7160)=40.9, P<0.001) and HVLT-R (F(7160)=62.5, P<0.001) between the four groups, indicating that the cognitive functioning in the UHR group was intermediate between the FE and FDR groups, while the FDR group had poorer performance than the HC group, and the FE group had the poorest cognitive functioning across all four examined domains. CONCLUSION: The results indicate that impairments in processing speed, attention, working memory and verbal memory exist in both UHR and FDR subjects. In order to clarify the associations between cognitive functioning and UHR and schizophrenia, longitudinal studies are warranted. PMID- 27197906 TI - Screening Strategies for Unrecognized CKD. PMID- 27197905 TI - The See Kidney Disease Targeted Screening Program for CKD. AB - BACKGROUND AND OBJECTIVES: The effectiveness of targeted screening for identification of CKD is largely unknown. The See Kidney Disease (SeeKD) targeted screening project aimed to determine the prevalence of unrecognized CKD in Canada. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The SeeKD project was conducted across Canada using a convenience sample approach and events to identify adults with risk factors for CKD (i.e., diabetes, hypertension, vascular disease, family history of kidney problems, etc.). Participants with at least one risk factor received a point-of-care creatinine measurement to identify unrecognized CKD (CKD-Epidemiology Collaboration eGFR <60 ml/min per 1.73 m(2)). Baseline information included clinical characteristics, sociodemographics, and health knowledge. Semistructured telephone interviews were conducted with each Kidney Foundation of Canada branch (regionalized locations) after the screening events to characterize local screening strategies, which were subsequently categorized as individual-targeted (specifically targeting individuals at risk of CKD) and community-targeted (event in a community location in proximity to a high risk population). We calculated the prevalence of unrecognized CKD overall, and by screening strategy. RESULTS: Between January 2011 and February 2014, 6329 Canadians participated in SeeKD screening events. Participants were predominantly female (65.3%), middle-aged (mean, 58.5 years), and the majority (88.9%) self reported at least one risk factor for CKD. Of participants with at least one risk factor, 92.3% (n=5194) were screened, of whom 18.8% (95% confidence interval [95% CI], 17.8 to 19.9) had unrecognized CKD; the majority (13.8%) had stage 3a CKD (eGFR=45-60 ml/min per 1.73 m(2)). The prevalence of unrecognized CKD was higher for branches with individual versus community-targeted events (21.9% [95% CI, 20.5 to 23.4] versus 14.7% [95% CI, 13.2 to 16.2]). CONCLUSIONS: Targeted screening identified a high proportion of individuals with risk factors for CKD and a high prevalence of unrecognized CKD. Future research will evaluate the ability of targeted screening to promote self-management behaviors addressing priorities for people with CKD. PMID- 27197909 TI - Strategies for BP Control in Developing Countries and Effects on Kidney Function. PMID- 27197908 TI - Health Education and General Practitioner Training in Hypertension Management: Long-Term Effects on Kidney Function. AB - BACKGROUND AND OBJECTIVES: In the Control of Blood Pressure and Risk Attenuation trial, a 2*2 factorial design study (2004-2007), the combined home health education and trained general practitioner intervention delivered over 2 years was more effective than no intervention (usual care) in lowering systolic BP among adults with hypertension in urban Pakistan. We aimed to assess the effectiveness of the interventions on kidney function. DESIGN, PARTICIPANTS, SETTINGS, & METHODS: In 2012-2013, we conducted extended follow-up of a total of 1271 individuals aged >=40 years with hypertension (systolic BP >=140 mmHg, diastolic BP >=90 mmHg, or receipt of antihypertensive treatment) and serum creatinine measurements with 2 years in-trial and 5 years of post-trial period in 12 randomly selected low-income communities in Karachi, Pakistan. The change in eGFR from baseline to 7 years was assessed among randomized groups using a generalized estimating equation method with multiple imputation of missing values. RESULTS: At 7 years of follow-up, adjusted mean eGFR remained unchanged, with a change of -0.3 (95% confidence interval [95% CI], -3.5 to 2.9) ml/min per 1.73 m(2) among adults randomly assigned to the combined home health education plus trained general practitioner intervention compared with a significant decline of -3.6 (95% CI, -5.7 to -2.0) ml/min per 1.73 m(2) in those assigned to usual care (P=0.01, modified intention-to-treat analysis). The risk for the combined intervention of death from kidney failure or >20% decline in eGFR relative to usual care was significantly reduced (risk ratio, 0.47; 95% CI, 0.25 to 0.89). CONCLUSIONS: The combined home health education plus trained general practitioner intervention is beneficial in preserving kidney function among adults with hypertension in communities in Karachi. These findings highlight the importance of scaling up simple strategies for renal risk reduction in low- and middle-income countries. PMID- 27197907 TI - Pharmacokinetics and Pharmacodynamics of Extended Infusion Versus Short Infusion Piperacillin-Tazobactam in Critically Ill Patients Undergoing CRRT. AB - BACKGROUND AND OBJECTIVES: Infection is the most common cause of death in severe AKI, but many patients receiving continuous RRT do not reach target antibiotic concentrations in plasma. Extended infusion of beta-lactams is associated with improved target attainment in critically ill patients; thus, we hypothesized that extended infusion piperacillin-tazobactam would improve piperacillin target attainment compared with short infusion in patients receiving continuous RRT. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted an institutional review board-approved observational cohort study of piperacillin-tazobactam pharmacokinetics and pharmacodynamics in critically ill patients receiving continuous venovenous hemodialysis and hemodiafiltration at three tertiary care hospitals between 2007 and 2015. Antibiotic concentrations in blood and/or dialysate samples were measured by liquid chromatography, and one- and two compartment pharmacokinetic models were fitted to the data using nonlinear mixed effects regression. Target attainment for piperacillin was defined as achieving four times the minimum inhibitory concentration of 16 MUg/ml for >50% of the dosing cycle. The probabilities of target attainment for a range of doses, frequencies, and infusion durations were estimated using a Monte Carlo simulation method. Target attainment was also examined as a function of patient weight and continuous RRT effluent rate. RESULTS: Sixty-eight participants had data for analysis. Regardless of infusion duration, 6 g/d piperacillin was associated with <=45% target attainment, whereas 12 g/d was associated with >=95% target attainment. For 8 and 9 g/d, target attainment ranged between 68% and 85%. The probability of target attainment was lower at higher effluent rates and patient weights. For all doses, frequencies, patient weights, and continuous RRT effluent rates, extended infusion was associated with higher probability of target attainment compared with short infusion. CONCLUSIONS: Extended infusions of piperacillin-tazobactam are associated with greater probability of target attainment in patients receiving continuous RRT. PMID- 27197910 TI - The Role of RRT in Hyperammonemic Patients. AB - Hyperammonemia is an important cause of cerebral edema in both adults with liver failure and children with inborn errors of metabolism. There are few studies that have analyzed the role of extracorporeal dialysis in reducing blood ammonia levels in the adult population. Furthermore, there are no firm guidelines about when to implement RRT, because many of the conditions that are characterized by hyperammonemia are extremely rare. In this review of existing literature on RRT, we present the body's own mechanisms for clearing ammonia as well as the dialytic properties of ammonia. We review the available literature on the use of continuous venovenous hemofiltration, peritoneal dialysis, and hemodialysis in neonates and adults with conditions characterized by hyperammonemia and discuss some of the controversies that exist over selecting one modality over another. PMID- 27197911 TI - Patient and Other Stakeholder Engagement in Patient-Centered Outcomes Research Institute Funded Studies of Patients with Kidney Diseases. AB - Including target populations in the design and implementation of research trials has been one response to the growing health disparities endemic to our health care system, as well as an aid to study generalizability. One type of community based participatory research is "Patient Centered-Research", in which patient perspectives on the germane research questions and methodologies are incorporated into the study. The Patient-Centered Outcomes Research Institute (PCORI) has mandated that meaningful patient and stakeholder engagement be incorporated into all applications. As of March 2015, PCORI funded seven clinically-focused studies of patients with kidney disease. The goal of this paper is to synthesize the experiences of these studies to gain an understanding of how meaningful patient and stakeholder engagement can occur in clinical research of kidney diseases, and what the key barriers are to its implementation. Our collective experience suggests that successful implementation of a patient- and stakeholder-engaged research paradigm involves: (1) defining the roles and process for the incorporation of input; (2) identifying the particular patients and other stakeholders; (3) engaging patients and other stakeholders so they appreciate the value of their own participation and have personal investment in the research process; and (4) overcoming barriers and challenges that arise and threaten the productivity of the collaboration. It is our hope that the experiences of these studies will further interest and capacity for incorporating patient and stakeholder perspectives in research of kidney diseases. PMID- 27197913 TI - Beyond APOL1: Genetic Inroads into Understanding Population Disparities in Diabetic Kidney Disease. PMID- 27197912 TI - Association Analysis of the Cubilin (CUBN) and Megalin (LRP2) Genes with ESRD in African Americans. AB - BACKGROUND AND OBJECTIVES: Genetic variation in the cubilin (CUBN) gene is associated with albuminuria and CKD. Common and rare coding variants in CUBN and the gene encoding its transport partner megalin (LRP2) were assessed for association with ESRD in blacks. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Sixty-six CUBN and LRP2 single-nucleotide polymorphisms (SNPs) were selected and analyzed in this multistage study. Exome sequencing data from 529 blacks with type 2 diabetes (T2D) -associated ESRD and 535 controls lacking T2D or nephropathy (the Type 2 Diabetes Genes [T2D-GENES] Consortium) were first evaluated, focusing on coding variants in CUBN and LRP2; 15 potentially associated SNPs identified from the T2D-GENES Consortium as well as 51 other selected SNPs were then assessed in an independent T2D-ESRD sample set of blacks (the Affymetrix Axiom Biobank Genotyping Array [AXIOM]; 2041 patients with T2D ESRD, 627 patients with T2D without nephropathy, and 1140 nondiabetic, non nephropathy controls). A meta-analysis combining the T2D-GENES Consortium and the AXIOM data was performed for 18 overlapping SNPs. Additionally, all 66 SNPs were genotyped in the Wake Forest School of Medicine samples of blacks with nondiabetic ESRD (885 patients with nondiabetic ESRD and 721 controls). Association testing with ESRD was performed in models including age, sex, African ancestry proportion, and apolipoprotein L1 gene renal-risk variants. RESULTS: CUBN SNP rs1801239 (I2984V), previously associated with albuminuria, was significantly associated with T2D-ESRD in blacks (the T2D-GENES Consortium and the AXIOM meta-analysis, P=0.03; odds ratio, 1.31; 95% confidence interval, 1.03 to 1.67; minor allele frequency =0.028). A novel LRP2 missense variant, rs17848169 (N2632D), was also significantly protective from T2D-ESRD (the T2D GENES Consortium and the AXIOM, P<0.002; odds ratio, 0.47; 95% confidence interval, 0.29 to 0.75; meta-analysis minor allele frequency =0.007). Neither SNP was associated with T2D when contrasting patients with T2D with controls lacking diabetes. CUBN and LRP2 SNPs were not associated with nondiabetic etiologies of ESRD. CONCLUSIONS: Evidence for genetic association exists between a cubilin and a rare megalin variant with diabetes-associated ESRD in populations with recent African ancestry. PMID- 27197914 TI - Pragmatic study designs for older adults with cancer: Report from the U13 conference. AB - Cancer is a disease occurring disproportionately in older adults. However, the evidence base regarding how best to care for these patients remains limited due to their underrepresentation in cancer clinical trials. Pragmatic clinical trials represent a promising approach for enhancing the evidence base in geriatric oncology by allowing investigators to enroll older, frailer patients onto cancer clinical trials. These trials are more accessible, less resource intensive, and place minimal additional burden on participating patients. Additionally, these trials can be designed to measure endpoints directly relevant to older adults, such as quality of life, functional independence and treatment tolerability which are often not addressed in standard clinical trials. Therefore, pragmatic clinical trials allow researchers to include patients for whom the treatment will ultimately be applied and to utilize meaningful endpoints. Examples of pragmatic studies include both large, simple trials and cluster randomized trials. These study designs allow investigators to conduct clinical trials within the context of everyday practice. Further, researchers can devise these studies to place minimal burden on the patient, the treating clinicians and the participating institutions. In order to be successful, pragmatic trials must efficiently utilize the electronic medical record for data capture while also maximizing patient recruitment, enrollment and retention. Additionally, by strategically utilizing pragmatic clinical trials to test therapies and interventions that have previously shown efficacy in younger, fitter patients, these trials represent a potential mechanism to improve the evidence base in geriatric oncology and enhance care for older adults with cancer. PMID- 27197915 TI - Geriatric assessment with management in cancer care: Current evidence and potential mechanisms for future research. AB - Older adults with cancer represent a complex patient population. Geriatric assessment (GA) is recommended to evaluate the medical and supportive care needs of this group. "GA with management" is a term encompassing the resultant medical decisions and interventions implemented in response to vulnerabilities identified on GA. In older, non-cancer patients, GA with management has been shown to improve a variety of outcomes, such as reducing functional decline and health care utilization. However, the role of GA with management in the older adult with cancer is less well established. Rigorous clinical trials of GA with management are necessary to develop an evidence base and support its use in the routine oncology care of older adults. At the recent U-13 conference, "Design and Implementation of Intervention Studies to Improve or Maintain Quality of Survivorship in Older and/or Frail Adults with Cancer," a session was dedicated to developing research priorities in GA with management. Here we summarize identified knowledge gaps in GA with management studies for older patients with cancer and propose areas for future research. PMID- 27197916 TI - Designing exercise clinical trials for older adults with cancer: Recommendations from 2015 Cancer and Aging Research Group NCI U13 Meeting. AB - Cancer and its treatment can lead to a myriad of adverse events and negatively impact quality of life of older cancer patients and survivors. Unmet physical activity needs vary across the cancer continuum and remain an important yet understudied area of research in this population. Exercise interventions have been shown to be effective in treating both the physical and psychological declines associated with cancer and its treatment, with a potential to improve cancer-related outcomes. Despite the current evidence, exercise is clearly underutilized due to several barriers and knowledge gaps in existing trials that include appropriate population identification, design, and outcome measures selection. The benefits of regular exercise in both the primary and secondary prevention of chronic conditions are well established in the non-cancer population. In older cancer patients and survivors, further research is needed before exercise gains widespread acceptance. The Cancer and Aging Research Group convened experts in exercise, aging and cancer to evaluate current scientific evidence and knowledge gaps in geriatric exercise oncology. This report summarizes these findings and provides future research directions. PMID- 27197917 TI - Interventions to improve the quality of life and survivorship of older adults with cancer: The funding landscape at NIH, ACS and PCORI. AB - Identifying knowledge gaps and research opportunities in cancer and aging research was the focus of a three-part conference series led by the Cancer and Aging Research Group from 2010 to 2015. The third meeting, featured representatives from the NIA, NCI, ACS and PCORI each of whom discussed research priorities and funding opportunities in cancer and aging at their respective agencies. This manuscript reports on the proceedings of that conference with a specific focus on funding priorities for interventions to improve the quality of life and survivorship of older adults with cancer. Helpful tips from each funder regarding writing a scientifically strong research proposal are presented. PMID- 27197918 TI - Chemotherapy-related cognitive impairment in older patients with cancer. AB - Chemotherapy-related cognitive impairment (CRCI) can occur during or after chemotherapy and represents a concern for many patients with cancer. Among older patients with cancer, in whom there is little clinical trial evidence examining side effects like CRCI, many unanswered questions remain regarding risk for and resulting adverse outcomes from CRCI. Given the rising incidence of cancer with age, CRCI is of particular concern for older patients with cancer who receive treatment. Therefore, research related to CRCI in older patients with cancers is a high priority. In this manuscript, we discuss current gaps in research highlighting the lack of clinical studies of CRCI in older adults, the complex mechanisms of CRCI, and the challenges in measuring cognitive impairment in older patients with cancer. Although we focus on CRCI, we also discuss cognitive impairment related to cancer itself and other treatment modalities. We highlight several research priorities to improve the study of CRCI in older patients with cancer. PMID- 27197920 TI - Benefits of robotic cystectomy with intracorporeal diversion for patients with low cardiorespiratory fitness: A prospective cohort study. AB - BACKGROUND: Patients undergoing radical cystectomy have associated comorbidities resulting in reduced cardiorespiratory fitness. Preoperative cardiopulmonary exercise testing (CPET) measures including anaerobic threshold (AT) can predict major adverse events (MAE) and hospital length of stay (LOS) for patients undergoing open and robotic cystectomy with extracorporeal diversion. Our objective was to determine the relationship between CPET measures and outcome in patients undergoing robotic radical cystectomy and intracorporeal diversion (intracorporeal robotic assisted radical cystectomy [iRARC]). METHODS: A single institution prospective cohort study in patients undergoing iRARC for muscle invasive and high-grade bladder cancer. INCLUSION: patients undergoing standardised CPET before iRARC. EXCLUSIONS: patients not consenting to data collection. Data on CPET measures (AT, ventilatory equivalent for carbon dioxide [VE/VCO2] at AT, peak oxygen uptake [VO2]), and patient demographics prospectively collected. Outcome measurements included hospital LOS; 30-day MAE and 90-day mortality data, which were prospectively recorded. Descriptive and regression analyses were used to assess whether CPET measures were associated with or predicted outcomes. RESULTS: From June 2011 to March 2015, 128 patients underwent radical cystectomy (open cystectomy, n = 17; iRARC, n = 111). A total of 82 patients who underwent iRARC and CPET and consented to participation were included. Median (interquartile range): age = 65 (58-73); body mass index = 27 (23-30); AT = 10.0 (9-11), Peak VO2 = 15.0 (13-18.5), VE/VCO2 (AT) = 33.0 (30 38). 30-day MAE = 14/111 (12.6%): death = 2, multiorgan failure = 2, abscess = 2, gastrointestinal = 2, renal = 6; 90-day mortality = 3/111 (2.7%). AT, peak VO2, and VE/VCO2 (at AT) were not significant predictors of 30-day MAE or LOS. The results are limited by the absence of control group undergoing open surgery. CONCLUSIONS: Poor cardiorespiratory fitness does not predict increased hospital LOS or MAEs in patients undergoing iRARC. Overall, MAE and LOS comparable with other series. PMID- 27197921 TI - Magnetic resonance/transrectal ultrasound fusion biopsy of the prostate compared to systematic 12-core biopsy for the diagnosis and characterization of prostate cancer: multi-institutional retrospective analysis of 389 patients. AB - OBJECTIVE: To determine the incremental diagnostic value of targeted biopsies added to an extended sextant biopsy scheme on a per-patient, risk-stratified basis in 2 academic centers using different multiparametric magnetic resonance imaging (MRI) protocols, a large group of radiologists, multiple biopsy systems, and different biopsy operators. MATERIALS AND METHODS: All patients with suspected prostate cancer (PCa) who underwent multiparametric MRI of the prostate in 2 academic centers between February 2013 and January 2015 followed by systematic and targeted MRI-transrectal ultrasound fusion biopsy were reviewed. Risk-stratified detection rate using systematic biopsies was compared with targeted biopsies on a per-patient basis. The McNemar test was used to compare diagnostic performance of the 2 approaches. RESULTS: A total of 389 men met eligibility criteria. PCa was diagnosed in 47% (182/389), 52%(202/389), and 60%(235/389) of patients using the targeted, systematic, and combined (targeted plus systematic) approach, respectively. Compared with systematic biopsy, targeted biopsy diagnosed 11% (37 vs. 26) more intermediate-to-high risk (P<0.0001) and 16% (10 vs. 16) fewer low-risk tumors (P<0.0001). These results were replicated when data from each center, biopsy-naive patients, and men with previous negative biopsies were analyzed separately. CONCLUSION: Targeted MRI transrectal ultrasound fusion biopsy consistently improved the detection of clinically significant PCa in a large patient cohort with diverse equipment, protocols, radiologists, and biopsy operators as can be encountered in clinical practice. PMID- 27197919 TI - Gaps in nutritional research among older adults with cancer. AB - Nutritional issues among older adults with cancer are an understudied area of research despite significant prognostic implications for treatment side effects, cancer-specific mortality, and overall survival. In May of 2015, the National Cancer Institute and the National Institute on Aging co-sponsored a conference focused on future directions in geriatric oncology research. Nutritional research among older adults with cancer was highlighted as a major area of concern as most nutritional cancer research has been conducted among younger adults, with limited evidence to guide the care of nutritional issues among older adults with cancer. Cancer diagnoses among older adults are increasing, and the care of the older adult with cancer is complicated due to multimorbidity, heterogeneous functional status, polypharmacy, deficits in cognitive and mental health, and several other non-cancer factors. Due to this complexity, nutritional needs are dynamic, multifaceted, and dependent on the clinical scenario. This manuscript outlines the proceedings of this conference including knowledge gaps and recommendations for future nutritional research among older adults with cancer. Three common clinical scenarios encountered by oncologists include (1) weight loss during anti cancer therapy, (2) malnutrition during advanced disease, and (3) obesity during survivorship. In this manuscript, we provide a brief overview of relevant cancer literature within these three areas, knowledge gaps that exist, and recommendations for future research. PMID- 27197923 TI - A delayed diagnosis of salt-wasting congenital adrenal hyperplasia. PMID- 27197925 TI - Association between maternal genital mycoplasma colonization and histologic chorioamnionitis in preterm births. AB - OBJECTIVE: Genital mycoplasmas (GMs) can be associated with chorioamnionitis and preterm birth, but are viewed as commensal organisms with low virulence. We sought to determine if cervical GM colonization is associated with histologic chorioamnionitis independent of infection with other bacteria. STUDY DESIGN: Retrospective study of patients who delivered preterm, had cervical cultures for GMs, and placental cultures for bacteria other than GM. GM positive patients were compared to GM negative patients. Histologic grading of placentas was compared between GM negative patients with negative placental cultures (Group 1), GM positive patients with negative placental cultures (Group 2), GM negative patients with positive placental cultures (Group 3) and GM positive patients with positive placental cultures (Group 4). RESULTS: GM positive patients were less likely than GM negative patients to have placental cultures positive for other bacteria (39% versus 47%, P = 0.0071). Group 2 had higher rates of membrane inflammation compared to Group 1 (p = 0.0079), and no significant difference in rates of membrane inflammation compared to Groups 3 or 4 (p = 0.36, p = 0.18). GM positivity was independently associated with increased membrane inflammation and decreased inflammation in the chorionic plate. CONCLUSIONS: GM colonization is associated decreased inflammation of the chorionic plate, and increased inflammation of the membranes. PMID- 27197926 TI - Severe laryngeal stenosis in newly born twins with 22q11.2 deletion syndrome: A case report. AB - Chromosome 22q11.2 deletion syndrome is common and presents with a range of clinical features from cardiac malformations to hypocalcemia. Laryngeal anomalies are not a common feature of this syndrome. We describe newly born twins who presented with unexpected severe birth depression secondary to severe type IV glottic webs requiring extensive resuscitation and emergency tracheostomy. They were diagnosed postnatally to have deletion of 22q11.2. The successful resuscitation of these infants at birth was only possible because they were born in a tertiary care hospital. This report shows the critical nature of prenatal diagnosis of 22q11.2 deletion syndrome. PMID- 27197924 TI - Agroindustrial composts to reduce the use of peat and fungicides in the cultivation of muskmelon seedlings. AB - BACKGROUND: Environmental concerns about peat extraction in wetland ecosystems have increased. Therefore, there is an international effort to evaluate alternative organic substrates for the partial substitution of peat. The aim of this work was to use different composts (C1-C10) obtained from the fruit and vegetable processing industry (pepper, carrot, broccoli, orange, artichoke residues, sewage sludge (citric and pepper) and vineyard pruning wastes) to produce added-value composts as growing media with suppressive effect against Fusarium oxysporum f.sp. melonis (FOM) in muskmelon. RESULTS: Composts showed values of water-soluble carbon fractions and dehydrogenase activity that allowed them to be considered mature and stabilized. All compost treatments produced significantly (F = 7.382; P < 0.05) higher fresh shoot weight than peat, treatment T-C2 showing the highest values. Treatments T-C5, T-C7 and T-C8 showed percentages of disease incidence that were significantly (F = 16.052; P < 0.05) the lowest, relative to peat, followed by T-C6, T-C10, T-C1 and T-C9 with values below 50%. CONCLUSION: Composts produced are suitable components of mixed compost peat growing media, providing a 50% substitution of peat. Furthermore, some of these composts also showed an added value as a suppressive organic medium against Fusarium wilt in muskmelon seedling, a fact probably related to high pH and pepper wastes and high content of pruning waste as initial raw materials. (c) 2016 Society of Chemical Industry. PMID- 27197927 TI - Endothelin-1 levels and renal function in newborns of various gestational ages. AB - BACKGROUND: Renal failure is common in the NICU; Acute Kidney Injury (AKI) occurs in 8-24% of admissions. Although AKI is preventable with early diagnosis, no reliable AKI biomarkers exist. Endothelin-1 (ET-1) has been implicated in renal pathogenesis, and elevated urinary ET-1 (uET-1) levels may correlate with progression of renal dysfunction. The study objectives were to determine whether uET-1 levels correlate with renal function parameters and/or fetal growth restriction, and if uET-1 is a potential neonatal AKI biomarker. METHODS: Sixty three neonates were enrolled and divided into gestational age (GA) groups by weeks: 1) (24-30 6/7; n = 24); 2) (31-36 6/7; n = 26); and 3) (37-42; n = 13). Additional preterm subgroups for fetal growth restriction analysis included: 1) Appropriate for GA (AGA; n = 40), and 2) Small for GA (SGA; n = 10). ET-1 levels, measured using enzyme linked immunosorbent assay, were collected at birth (cord blood) and 24 h ( +/- 4) of life (blood/urine). RESULTS: No correlation was found between uET-1 and blood plasma levels at birth (r = 0.15; p > 0.05) or 24 h (r = 0.17; p > 0.05). uET-1 negatively correlated with GA (r = -0.44; p < 0.001) and GFR (r = -0.34; p < 0.01). uET-1 levels did not correlate with creatinine (r = 0.13; p > 0.05), BUN (r = 0.19; p > 0.05), BUN/Cr ratio (r = 0.15; p > 0.05), or urinary output (r = 0.12; p > 0.05). In fetal growth restriction subgroup analyses: uET-1 levels negatively correlated with GFR in the PT-AGA subgroup (r = -0.38; p = 0.017), but not with PT-SGA (r = 0.01; p > 0.05). CONCLUSION: Plasma and uET-1 levels did not correlate; therefore, renal ET-1 excretion may reflect renal ET-1 production. uET-1 levels correlated negatively with GA and GFR. uET-1 may be a marker of impaired neonatal circulatory regulation and consequent renal injury. PMID- 27197928 TI - PIVKA-II correlates with INR but not protein C or protein S concentrations in cord blood among newborns. AB - BACKGROUND: Protein induced by vitamin K absence (PIVKA)-II, inactive precursor of prothrombin, is elevated in vitamin K (VK) deficiency. Our aims were to find the prevalence of VK deficiency in neonates, assess the utility of international normalized ratio (INR) as a screening tool, and explore the relationship between PIVKA-II, activated partial thromboplastin time (aPTT) and VK dependent anticoagulants. METHODS: INR, aPTT, PIVKA-II, and proteins C and S activities were measured in neonatal cord blood prior to VK administration. RESULTS: We found 45% of neonates had subclinical VK deficiency based on PIVKA-II levels and 7% based on INR. Receiver operating characteristic (ROC) analysis assessed the utility of INR in detecting >4 ng/mL of PIVKA-II and ROC of the area under the curve was 0.70 (95% CI 0.46-0.92, p = 0.07). Proteins C and S activities were normal for age and did not correlate with PIVKA-II [(r = 0.40, p = 0.14) and (r = 0.29, p = 0.29), respectively]. There was no association between aPTT and PIVKA II (p = 0.83). CONCLUSION: PIVKA-II seems to be a sensitive indicator of mild VK deficiency. Further studies are needed to investigate the lack of relationship between PIVKA-II and functional protein C or S levels. PMID- 27197929 TI - Therapeutic hypothermia for infants with hypoxic ischemic encephalopathy: A five years' single center experience in Kuwait. AB - OBJECTIVE: We aimed to evaluate the effect of therapeutic hypothermia (TH) on brain MRI findings, neurological outcome, and mortality in patients with perinatal hypoxic ischemic encephalopathy (HIE) and compare between two modalities of TH: whole body cooling (WBC) and selective head cooling (SHC). PATIENTS AND METHODS: Sixty-two inborn babies with HIE admitted to the NICU of a Kuwaiti teaching hospital between 2006 and 2013 were retrospectively reviewed. Patients were divided into two groups: group 1 (2006-2008, n = 30) never received hypothermia, and group 2 (2009-2013, n = 32) treated with hypothermia. Group 2 patients were chronologically divided into two subgroups: 2a, the SHC, (2009 2010, n = 15) and 2b, the WBC, (2011-2013, n = 17). Brain MRI taken 7-10 days after birth, neurological status and mortality at time of hospital discharge were evaluated. RESULTS: Patients who received TH showed significantly fewer MRI hypoxic changes (P = 0.04) and had better neurological outcome. Their need for anticonvulsants diminished (P = 0.04). However, their need for inotropes and duration of mechanical ventilation were increased (P = 0.001 & 0.02 respectively). No significant difference in mortality was found between the two groups (P = 0.6). In regression analysis, only MRI hypoxic changes predicted the occurrence of neurological abnormalities (P = 0.001). No difference in brain MRI findings, neurological outcome and mortality was observed between subgroups 2a and 2b (P > 0.05). CONCLUSION: TH improved the neurological outcome of HIE patients but had no effect on mortality. There was no difference between the two modalities of TH on patients' outcome. PMID- 27197930 TI - Perinatal outcome comparing triplets and singleton births at a reference maternity hospital. AB - OBJECTIVE: The objective of the present study was to evaluate adverse perinatal outcome in a group of high order pregnancies pared with singletons by BW and GA at birth. METHODS: Data was reviewed for all admissions of triplets and quadruplets in a 7 year period. For each study neonate we selected two singleton infants to constitute a control group. Variables analyzed included: respiratory distress syndrome, patent ductus arteriosus, intraventricular hemorrhage, necrotizing enterocolitis (NEC), bronchopulmonary dysplasia, retinopathy of prematurity and periventricular leukomalacia. RESULTS: We studied a total of 128 multiple and 260 singleton infants. Mean gestational age and birth weight were similar in both groups (31.3 +/- 2,5 wks e 31.5 +/- 2,8 wks; 1470 +/- 461 g vs 1495 +/- 540 g). There was no significant difference between the groups in the majority of main morbidities. The incidence of NEC was higher in triplets (6.3 vs 0.8%, p value <0.01). Mortality was higher in singletons (9.6 vs 3.1%, p value <0.037). CONCLUSIONS: Results show that major neonatal outcomes are very similar between multiples and singletons births when paired by gestational age and birth weight. NEC remained a significant morbidity in infants born from multiple gestations after adjustment for maternal and neonatal risk factors. PMID- 27197931 TI - Noninvasive inhaled nitric oxide for persistent pulmonary hypertension of the newborn: A single center experience. AB - INTRODUCTION: Nitric oxide is a potent, selective pulmonary vasodilator that has been proven to decrease pulmonary vascular resistance and has been part of the treatment arsenal for persistent pulmonary hypertension of the newborn (PPHN). In 2009, the approach to the administration of inhaled nitric oxide (iNO) at Winnie Palmer Hospital for Women and Babies (WPH) changed to emphasize avoiding invasive ventilation while maintaining optimal ventilation to perfusion ratio, avoiding hyperventilation and alkalosis agents, and avoiding hyperoxemia and hyperoxia exposure. Our aim is to describe the outcomes of babies whose primary treatment for PPHN was noninvasive (NIV) iNO. METHODS: A retrospective chart review of neonates born at WPH from October 1, 2009 through October 1, 2014. INCLUSION CRITERIA: >34 weeks' gestation, echocardiographic evidence of PPHN within the first week of life, and NIV iNO as the primary treatment. RESULTS: Twenty-four babies met criteria: 21 solely treated noninvasively, 3 required invasive support. Supplemental oxygen need was >=50% for 21 babies pre-iNO treatment and dropped to <30% for all babies post-iNO. Average exposure to supplemental oxygen was 6.3 days. Mean duration of iNO administration was 2.5 days. Average length of stay was 14 days. All babies survived. CONCLUSION: Our review revealed a low incidence of escalation to invasive ventilation. Non-invasive iNO was found to be an effective and well-tolerated frontline approach for treating PPHN in near-term and term infants with an intact respiratory drive. Further studies could provide the necessary evidence on clinical outcomes as well as cost effectiveness to guide best practice. PMID- 27197922 TI - Prospects for Creation of Cardioprotective and Antiarrhythmic Drugs Based on Opioid Receptor Agonists. AB - It has now been demonstrated that the MU, delta1 , delta2 , and kappa1 opioid receptor (OR) agonists represent the most promising group of opioids for the creation of drugs enhancing cardiac tolerance to the detrimental effects of ischemia/reperfusion (I/R). Opioids are able to prevent necrosis and apoptosis of cardiomyocytes during I/R and improve cardiac contractility in the reperfusion period. The OR agonists exert an infarct-reducing effect with prophylactic administration and prevent reperfusion-induced cardiomyocyte death when ischemic injury of heart has already occurred; that is, opioids can mimic preconditioning and postconditioning phenomena. Furthermore, opioids are also effective in preventing ischemia-induced arrhythmias. PMID- 27197932 TI - Chronic lung disease in very low birth weight infants: Persistence and improvement of a quality improvement process in a tertiary level neonatal intensive care unit. AB - OBJECTIVE: We previously demonstrated a significant reduction in our incidence of chronic lung disease in our NICU using potentially better practices of avoiding delivery room endotracheal intubation and using early nasal CPAP. We sought to demonstrate whether these improvements were sustained and or improved over time. STUDY DESIGN: We conducted a retrospective, cross-sectional analysis of infants 501-1500 grams born at our hospital between 2005 and 2013. Infants born during the 2005-2007, 2008-2010 and 2011-2013 epochs were grouped together, respectively. Descriptive analysis was conducted to determine the number and percent of maternal and neonatal characteristics by year grouping. Chi-squared tests were used to determine whether there were any statistically significant changes in characteristics across year groupings.. Two outcome variables were assessed: a diagnosis of chronic lung disease based on the Vermont Oxford Network definition and being discharged home on supplemental oxygen. RESULTS: There was a statistically significant improvement in the incidence of chronic lung disease in infants below 27 weeks' gestation in the three year period in the 2011-2013 cohort compared with those in the 2005-2007 cohort. We also found a statistically significant improvement in the number of infants discharged on home oxygen with birth weights 751-1000 grams and infants with gestational age less than 27 weeks in the 2011-2013 cohort compared to the 2005-2007 cohort. CONCLUSIONS: We demonstrated sustained improvement in our incidence of CLD between 2005 and 2013. We speculate that a multifaceted strategy of avoiding intubation and excessive oxygen in the delivery room, the early use of CPAP, as well as the use of volume targeted ventilation, when needed, may help significantly reduce the incidence of CLD. PMID- 27197933 TI - The antecedents and correlates of necrotizing enterocolitis and spontaneous intestinal perforation among infants born before the 28th week of gestation. AB - OBJECTIVE: To identify antecedents of "medical" necrotizing enterocolitis (mNEC), "surgical" NEC (sNEC), and spontaneous intestinal perforation (SIP) in newborns delivered before 28 weeks gestation. STUDY DESIGN: Prospective multicenter cohort study. During study period, 2002- 2004, women delivering before 28 weeks gestation at one of 14 participating institutions were enrolled. Well defined antenatal and postnatal variables were collected. Bivariate analyses were performed to identify candidates for developing multinomial multivariable time oriented logistic regression models. RESULTS: Of the 1320 infants, 5% had mNEC, 6% had sNEC, and 4% had SIP. Antecedents of mNEC included mother's identification as Black, consumption of aspirin during the pregnancy, and vaginal bleeding after the 12th week of gestation. For sNEC the antecedents were maternal self- support, obesity and anemia during the pregnancy, birth before the 24th week, birth weight <=750gm, and receipt of fresh frozen plasma (FFP) during the first postnatal week. An infant was at increased risk of SIP if the placenta had increased syncytial knots, birth occurred before the 24th week, and received FFP during the first week. CONCLUSIONS: Maternal and neonatal characteristics might help identify at-risk ELGANs for NEC and SIP, who then may potentially benefit from targeted preventive strategies. PMID- 27197934 TI - Prenatal diagnosis of sub-microscopic partial trisomy 10q using chromosomal microarray analysis in a phenotypically abnormal fetus with normal karyotype. AB - Partial trisomy of the 10q region was originally reported in 1979 [1]. For 25 years, the diagnosis was made microscopically based on large, visible insertions in the region identified by karyotype analysis. Previous case reports have included both unbalanced translocations and large duplications/insertions in the 10q region [2]. Probands with partial trisomy 10q syndrome often have an abnormal phenotype that may include developmental delay [3-5], craniofacial abnormalities [3, 5], talipes (clubfoot) [2], microcephaly [2-4], or congenital heart disease [2-6]. Prenatal diagnoses by karyotype have been made following ultrasound diagnosis of sacrococcygeal teratoma [7], renal pyelectasis [3, 8-10], and other fetal abnormalities [4]. In this case, we report the first prenatal diagnosis of partial trisomy 10q (10q22.3-10q23.2) with a normal karyotype and an abnormal chromosomal microarray analysis (CMA). This is the smallest copy number variant (CNV) (7.5 Mb) in the 10q22.3-10q23.2 regions yet reported. PMID- 27197935 TI - Ultrasound cervical length measurement in prediction of labor induction outcome. AB - Induction of labor is one of the most common procedures in modern obstetrics, with an incidence of approximately 20% of all deliveries. Not all of these inductions result in vaginal delivery; some lead to cesarean sections, either for emergency reasons or for failed induction. That's why, It seems necessary to outline strategies for the improvement of the success rate of induced deliveries. Traditionally, the identification of women in whom labor induction is more likely to be successful is based on the Bishop score. However, several studies have shown it to be subjective, with high variation and a poor predictor of the outcome of labor induction. Transvaginal sonography for cervical measurement can be a more objective criterion in assessing the success of labor induction. Many studies have been done recently to compare cervical measurement and Bishop Score in labor induction.This paper reviewed the literature that evaluated sonographic cervical length measurement to predict induction of labor outcome. PMID- 27197936 TI - Pulmonary interstitial glycogenosis in a patient with trisomy 21. AB - Pulmonary interstitial glycogenosis is an interstitial lung disease of childhood that has been increasingly reported over the past decade. Here, we present a case of pulmonary interstitial glycogenosis associated with trisomy 21, pulmonary arterial hypertension, and congenital heart disease in a 34 week premature infant. PMID- 27197937 TI - Obstetric hemorrhage survey: Attitudes and practices of maternal-fetal medicine fellows. AB - OBJECTIVE: To evaluate experiences related to obstetric hemorrhage and suspected abnormal placentation among first year maternal-fetal medicine fellows. STUDY DESIGN: A cross-sectional anonymous survey was administered at the Society for Maternal-Fetal Medicine fellow retreat in March 2013. Fellows were asked about management strategies that reflected both their individual and institutional practices. RESULTS: There was a 56% response rate (55/98). In cases of postpartum hemorrhage due to uterine atony, there was variable use of the uterine tamponade device. The median incremental time for balloon deflation was every 5 hours (IQR = 2-12). Compared to the east coast, fellows from the west coast performed more hysterectomies (mean+/-SD; 2.9+/-2.4 vs. 1.2+/-1.2, p = 0.004). During a peripartum hysterectomy, 29% of fellows used a handheld cautery device such as Ligasure(r) or Gyrus(r). Fifty-six percent responded that their institution never recommend planned delayed hysterectomies for abnormal placental implantation. CONCLUSION: There is wide variation in practice among first year maternal-fetal medicine fellows in management of peripartum hysterectomy and postpartum hemorrhage. PMID- 27197938 TI - Routine fecal occult blood testing does not predict necrotizing enterocolitis in very low birth weight neonates. AB - OBJECTIVE: To determine sensitivity, specificity, predictive value of routine fecal occult blood (FOB) testing on the identification of Bell's Stage II or III necrotizing enterocolitis (NEC) in very low birth weight (VLBW) infants. METHODS: Retrospective medical record review of VLBW infants from 2012- 2013 evaluating FOB results and clinical and demographic risk factors. We determined predictive values of positive FOB testing within 48 hours of definite NEC diagnosis. We performed logistic regression analyses for predictors of NEC and for predictors of having positive FOB during NICU admission. RESULTS: The incidence of NEC in our cohort of 203 infants was 3.9% (n = 8). None had positive FOB results within 48 hours of diagnosis, and only 12.5% had any positive FOB within 7 days. Sensitivity of positive FOB for predicting definite NEC = 0%, specificity = 34.4%, and positive predictive value = 0%. A majority of VLBWs (67.0%) had > one positive FOB result during their NICU course. On logistic regression, intrauterine growth restricted (IUGR) infants had significantly higher odds of both developing NEC and of having positive FOB. Positive FOB was not a significant predictor of NEC. Those with lower birth gestational ages had higher odds of positive FOB. CONCLUSIONS: Positive FOB testing occurred in a majority of VLBW infants, with higher odds in the more preterm and IUGR. However, the sensitivity, specificity, and predictive value of routine FOB testing for identifying NEC were all very poor. Our data demonstrates that this test offers no advantages in the early diagnosis of NEC. PMID- 27197939 TI - Use of Doppler velocimetry in diagnosis and prognosis of intrauterine growth restriction (IUGR): A Review. AB - Intrauterine growth restriction (IUGR) is a condition which has been difficult to assess at an early stage, resulting in the delivery of children who have poor genetic growth potential. Currently, IUGR classification is based upon the system of ultrasound biometry. Doppler velocimetry allows the measurement of hemodynamic flow of major fetal vessels, comparing the flow indices and patterns of normal and IUGR cases. In this review, the effectiveness of Doppler velocimetry in assessing blood flow in major vessels including the umbilical artery, ductus venosus, and middle cerebral artery was studied for both diagnostic and prognostic screening of IUGR. The umbilical artery is the most frequently studied vessel in Doppler velocimetry due to its accessibility and the strength of its associations with fetal outcomes. Abnormalities in the ductus venosus waveform can be indicative of increased resistance in the right atrium due to placental abnormalities. The middle cerebral artery is the most studied fetal cerebral artery and can detect cerebral blood flow and direction, which is why these three vessels were selected to be examined in this context. A potential mathematical model could be developed to incorporate these Doppler measurements which are indicative of IUGR, in order to reduce perinatal mortality. The purpose of the proposed algorithm is to integrate Doppler velocimetry with biophysical profiling in order to determine the optimal timing of delivery, thus reducing the risks of adverse perinatal outcomes. PMID- 27197940 TI - Heavy metal resistance and virulence profile in Pseudomonas aeruginosa isolated from Brazilian soils. AB - Pseudomonas aeruginosa is an opportunistic pathogen, which can have several virulence factors that confer on it the ability to cause severe, acute and chronic infections. Thus, the simultaneous occurrence of resistance to antibiotics and heavy metals associated with the presence of virulence genes is a potential threat to human health and environmental balance. This study aimed to investigate the resistance profile to heavy metals and the correlation of this phenotype of resistance to antimicrobials and to investigate the pathogenic potential of 46 P. aeruginosa isolates obtained from the soil of five Brazilian regions. The bacteria were evaluating for antimicrobial and heavy metal resistance, as well as the presence of plasmids and virulence genes. The isolates showed resistance to four different antibiotics and the majority (n = 44) had resistance to aztreonam or ticarcillin, furthermore, 32 isolates showed concomitant resistance to both of these antibiotics. A high prevalence of virulence genes was found, which highlights the pathogenic potential of the studied environmental isolates. Moreover, a high frequency of heavy metal resistance genes was also detected, however, the phenotypic results indicated that other genes and/or mechanisms should be related to heavy metal resistance. PMID- 27197941 TI - Five-year extended follow-up status of 10 patients with Dravet syndrome treated with fenfluramine. AB - Dravet syndrome (DS) is a rare and therapy-resistant epilepsy syndrome. A retrospective analysis of add-on fenfluramine treatment in 12 patients with DS was published in 2012 and provided evidence of a meaningful long-term response. Herein we present the results of a subsequent 5-year prospective observation of this original cohort. Ten patients with a mean current age of 24 years were followed prospectively from 2010 until 2014. The mean current dose of fenfluramine was 0.27 mg/kg/day, with a mean treatment duration of 16.1 years. Seizure frequency was derived from a seizure diary. Cardiac examinations and assessments of clinical effectiveness and adverse events were performed at least annually. Three patients were seizure-free for the entire 5 years, and an additional four patients experienced seizure-free intervals of at least 2 years. Fenfluramine was generally well-tolerated. Two patients had mild (stable) valve thickening on the last echocardiography that was deemed clinically insignificant. No patient had any clinical or echocardiographic signs of pulmonary hypertension. These findings support the long-term control of convulsive seizures by low-dose fenfluramine while being well tolerated in this cohort of patients with DS. After up to 27 years of treatment, no patient has developed any clinical signs or symptoms of cardiac valvulopathy or pulmonary hypertension. PMID- 27197942 TI - Self-Assembly Directed Organization of Nanodiamond During Ionic Liquid Crystalline Polymer Formation. AB - The UV-initiated free radical polymerization of a lyotropic mesophase prepared by co-assembly of an aqueous mixture of an ionic liquid (IL) monomer, 3-decyl-1 vinylimidazolium chloride, in a dimethyl sulfoxide dispersion of an IL-monomer nanodiamond conjugate yields a well-ordered 2D hexagonally structured network polymer composite. The IL monomer is covalently bound to carboxylated detonation diamond via ester-linked 3-decyl-1-vinylimidazolium bromide. Successful preparation of the amphiphile-functionalized nanodiamond is determined by ATR/FT IR, thermogravimetric analysis, and small-angle X-ray scattering (SAXS). Mesophase and composite structure are evaluated by SAXS, revealing a columnar architecture composed of amphiphilic ionic liquid cylinders containing solvent rich cores. Self-assembly directed site localization of the nanodiamond positions the particles in the alkyl chain continuum upon polymerization. The composite reversibly swells in ethanol allowing structural variation and modulation of the nanoparticle internal packing arrangement. This work demonstrates that through careful molecular design, self-organization and site-directed assembly of nanodiamond into chemically distinct regions of a nanostructured organogel can be achieved. PMID- 27197943 TI - Episodic Headache and Arachnoid Cyst Related Subdural Hematoma. PMID- 27197944 TI - How Electronic Excitation Can be Used to Inhibit Some Mechanisms Associated to Substituent Effects. AB - Despite the fact that transferability and chemistry go hand in hand, transferability studies in electronically excited states (EESs) are normally omitted, although these states are becoming extremely important in modern processes and applications. In this work, it is shown that this kind of studies can be used to understand how substituent effects can be modified in EESs. Thus, for example, the analysis of the carbonyl oxygen transferability in different HCO R molecules allowed us to find that the nO->piCO* excitation can be used to break the pi conjugation associated to the resonance substituent effect. Moreover, as a direct consequence, the oxygen transferability is enhanced in the first electronically excited state. PMID- 27197945 TI - The Flint Animal Cancer Center (FACC) Canine Tumour Cell Line Panel: a resource for veterinary drug discovery, comparative oncology and translational medicine. AB - Mammalian cell tissue culture has been a critical tool leading to our current understanding of cancer including many aspects of cellular transformation, growth and response to therapies. The current use of large panels of cell lines with associated phenotypic and genotypic information now allows for informatics approaches and in silico screens to rapidly test hypotheses based on simple as well as complex relationships. Current cell line panels with large amounts of associated drug sensitivity and genomics data are comprised of human cancer cell lines (i.e. NCI60 and GDSC). There is increased recognition of the contribution of canine cancer to comparative cancer research as a spontaneous large animal model with application in basic and translational studies. We have assembled a panel of canine cancer cell lines to facilitate studies in canine cancer and report here phenotypic and genotypic data associated with these cells. PMID- 27197947 TI - Liver transplantation in Spain. AB - Liver transplantation (LT) activity started in Spain in 1984 and has exceeded 23,700 interventions, with more than 1000 transplants performed yearly. Every hospital needs official authorization to perform a LT, which implies the obligation to register all patients on the national waiting list. The Spanish National Transplant Organization (ONT) provides essential support for organ procurement, allocation, and management of the waiting list at a national level. Liver allocation is center-oriented as all available organs are referred to the ONT for the whole country. The allocation rules for LT are made according to disease severity after consensus among professionals from every transplant center and ratified by representatives of the regional health authorities. Authorization and location/distribution of transplant centers are regulated by the country (Spain) and by the different regions according to the Real Decreto 1723/2012. For a total population of 47,850,795 inhabitants, there are 24 centers for LT for adults (1 team/2 million people) and 5 for LT for children (1 team/9.5 million people). Nonbiliary cirrhosis, particularly alcohol- and hepatitis C virus related cirrhosis (60%), and tumors, mainly hepatocellular carcinoma (19%), are the most common indications for LT in Spain. Unusual causes of LT include metabolic diseases like Wilson's disease, familial amyloid polyneuropathy and hyperoxaluria type I, polycystic kidney and liver disease, and some tumors (epithelioid hemangioendothelioma and neuroendocrine tumors). Important efforts are now being undertaken to improve the quality and transplantability of extended criteria livers, in particular those arising from DCD, which represent the greatest opportunity to expand the donor pool. These efforts have to be addressed to adapt the organ preservation procedures, be it through the application of regional perfusion in situ or the use of machine perfusion preservation ex situ. Liver Transplantation 22 1259-1264 2016 AASLD. PMID- 27197946 TI - The Burden of Sleep Problems: A Pilot Observational Study in an Ethnically Diverse Urban Primary Care Setting. AB - INTRODUCTION: Sleep disorders affect up to 1 in 4 adults and can adversely affect a variety of health conditions. However, little is known about detection of sleep disorders in ethnically diverse urban primary care settings. METHODS: Patients in urban primary care settings completed surveys to screen for sleep problems and identify comorbid conditions. Providers were given screening results, and provided feedback regarding their clinical utility. RESULTS: Participants (n = 95) were predominantly women (76.8%) and black, non-Hispanic (46.3%), or Hispanic (38.9%). High proportion of participants screened positive for insomnia (31.6%) and screened high risk for sleep apnea (42.1%). Only one-third (32.6%) of participants reported sleeping the recommended 7 to 9 hours per night. The presence of chronic pain (chi(2) = 4.97, P = .03) was associated with clinically significant insomnia. Obesity was associated with fewer hours of sleep per night, t = 2.19(87), P = .03, and risk for sleep apnea (OR = 3.11, 95% CI = 1.28-7.50). Participants were interested in receiving help for sleep issues during their primary care visits (40%), and providers found the screening at least somewhat useful (74.4%). DISCUSSION: Results highlight the potentially high unmet need for screening and treatment of sleep problems in ethnically diverse urban primary care settings. PMID- 27197948 TI - Editorial: Patent Ductus Arteriosus in Extremely Premature Neonates. PMID- 27197949 TI - Principles of Clinical Management of Patent Ductus Arteriosus in Extremely Preterm Neonates. AB - The clinical management of a patent ductus arteriosus (PDA) in preterm newborns is a controversial topic, and despite nearly three decades of research, varying opinions remain. This dilemma stems from uncertain causal linkage between PDA and neonatal comorbidities, as well as the lack of clear evidence showing that benefits of treatment outweigh risks. There has been a general shift in the management of PDA in preterm newborns from early and aggressive closure to a more conservative approach of watchful waiting and spontaneous closure. However, a firm recommendation cannot be made due to a lack of randomized controlled trials validating either treatment strategies. Although cyclooxygenase inhibitors, namely indomethacin and ibuprofen, are approved pharmacological treatments for PDA, there is a need to explore alternative medical therapies in view of lack of clinical response in many newborns and concerns over adverse effects. One such recent interest is the use of acetaminophen as a pharmacological agent. This present review tries to address the questions at hand, integrate the current evidence, highlight the principles of PDA management in preterm newborns, and suggest areas for possible future research. PMID- 27197950 TI - Patent Ductus Arteriosus in the Preterm Infant: An Update on Morbidity and Mortality. AB - BACKGROUND: Patent ductus arteriosus (PDA) is a common factor complicating the care of the preterm infant, but controversy remains regarding the long term effects of PDA and iatrogenic closure of PDA. METHODS: Studies presenting data relevant to the relationship between PDA and mortality and morbidity were identified via a systematic literature review. These studies were classified based on PDA exposure in the case and control groups. The data was abstracted and summarized using linear modeling, resulting in summary estimates of mean effect size (odds ratio). RESULTS: Recently published data suggests that a significant relationship between PDA and mortality, bronchopulmonary dysplasia/chronic lung disease, necrotizing enterocolitis, or retinopathy of prematurity is unlikely. However, the data related to mortality leaves room for some debate. Quantitative analysis of the data shows that PDA is a risk factor for intraventricular hemorrhage and related studies suggest this risk may carry over into long term neurological outcomes. CONCLUSION: Further efforts to better understand the physiologic consequences of PDA and its closure in preterm infants is necessary. A focus on new biochemical or physiologic factors that mediate or confound any apparent effect of PDA and are themselves amenable to targeted therapy is imperative to further progress in improving the outcomes of these patients. PMID- 27197951 TI - Nursing Assessment, Education, and Care of Extremely Premature Neonates with Patent Ductus Arteriosus. AB - The care of extremely premature neonates with suspected or confirmed diagnosis of patent ductus arteriosus (PDA) is a frequent challenge for pediatric nurses. It is important for nurses to have adequate knowledge of the normal postnatal changes in cardiovascular and pulmonary function to recognize any adverse symptoms. Nurses caring for these vulnerable neonates must have a thorough understanding of the pathophysiology of a PDA in order to assess, plan, and implement patient-centered care. Recognition of characteristic symptoms of PDA in a timely manner is essential for optimal management and outcomes. Understanding the science behind treatment options is also imperative for pediatric nurses to provide the best care and effectively educate parents. Pediatric nurses are a significant resource in managing extremely premature neonates through comprehensive assessment, effective parent education, and high-quality patient centered care. PMID- 27197952 TI - Pharmacotherapy for Patent Ductus Arteriosus: Current Options and Outstanding Questions. AB - Management of the patent ductus arteriosus (PDA) represents an ongoing challenge in the care of extremely premature neonates. Determining the optimal treatment strategy requires careful consideration of the potential risks and benefits of available therapies. Surgical ligation results in reliable ductal closure, but may result in numerous short-term complications and have a negative impact on long-term outcome. Intravenous indomethacin was the first pharmacologic agent widely utilized for PDA closure. Intravenous indomethacin effectively closes the ductus arteriosus and prevents pulmonary hemorrhage and severe intraventricular hemorrhage, but fails to mitigate short-term morbidities and improve long-term outcomes. Intravenous ibuprofen represents an alternative therapy with fewer renal adverse effects. However, intravenous ibuprofen does not prevent severe intraventricular hemorrhage and also has concerning adverse effects, including bilirubin displacement and the potential to increase the risk of chronic lung disease. Enteral ibuprofen has also been investigated, although gastrointestinal adverse effects limit widespread utilization. Acetaminophen (paracetamol) represents an enticing novel therapy due to wide availability, low cost, and an appealing safety profile. Ongoing investigation is required to determine the role of this agent in PDA treatment algorithms. Pending these results, clinicians must weigh the potential risks and benefits of each therapy for individual neonates considering all available evidence. PMID- 27197953 TI - Pathophysiology of Patent Ductus Arteriosus in the Preterm Infant. AB - The ductus arteriosus is a muscular artery connecting two elastic arteries with different resistances. It is a normal fetal structure that only becomes pathological if it remains patent after birth. A varied clinical impact is observed as some neonates may be asymptomatic, symptoms may be deferred until later in life, or the infant may be overtly symptomatic and present as early as the first days of life. Prematurity increases the likelihood of persistent ductal patency and is seen in about 30% of preterm infants. In premature neonates, patent ductus arteriosus (PDA) is associated with significant morbidity and mortality [1,2]. This discussion explains the pathophysiology behind the pathological events associated with PDA. PMID- 27197954 TI - Surgical Intervention in Preterm Neonates with Patent Ductus Arteriosus. AB - The ductus arteriosus is a fetal vascular connection between the pulmonary and systemic circulations. It fails to close after birth in a small number of term infants, and in a larger number of infants with cyanotic congenital heart disease. In contemporary practice the majority of patients present with a patent ductus arteriosus (PDA) are premature infants before the gestational age of 28 weeks. The surgical management of PDA in preterm infants is critical for optimal outcomes and is discussed in this article. PMID- 27197955 TI - Patent Ductus Arteriosus in Extreme Prematurity: Role of Echocar-diography and Other Imaging Techniques. AB - Clinical signs alone are unreliable in the diagnosis of patent ductus arteriosus (PDA) in preterm infants, and therefore echocardiography remains the mainstay of diagnosis of this common condition. Echocardiography also facilitates understanding of the hemodynamic effects of a PDA, and thus aids in management decisions. Several echocardiographic parameters, including duct size, maximum ductal velocity, left atrial: aorta ratio, mitral inflow E:A ratio, and isovolumic relaxation time, have been utilized in the assessment of PDA, but no single measurement can be used in isolation to inform clinical judgement. Therefore, it is important that echocardiographers on the neonatal unit have a comprehensive understanding of available methods and their limitations. Newer echocardiographic techniques, such as 3 Dimensional echocardiography, tissue Doppler imaging and strain imaging, are now providing insights into myocardial function in the adaptation of preterm infants to extra-uterine life, and into the effects of a PDA causing systemic-to-pulmonary artery shunting. Magnetic resonance imaging delivers excellent diagnostic information and accurate hemodynamic evaluation; however this modality is not easily accessible for most preterm infants, in comparison to echocardiography, which is readily available at the cotside in most neonatal units. Further developments in echocardiography may further refine the contribution it makes to individualized clinical decisionmaking in the management of premature infants with PDA. PMID- 27197956 TI - Structural grey matter changes in the substantia innominata in Alzheimer's disease and dementia with Lewy bodies: a DARTEL-VBM study. AB - OBJECTIVES: Several cholinergic nuclei, and in particular the nucleus basalis of Meynert, are localised to the substantia innominata in the basal forebrain. These nuclei provide major cholinergic innervation to the cerebral cortex and hippocampus, and have an essential role in cognitive function. The aim of this study was to investigate volumetric grey matter (GM) changes in the substantia innominata from structural T1 images in Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and healthy older participants using voxel-based morphometry. METHODS: Participants (41 DLB, 47 AD and 39 controls) underwent 3 T T1 magnetic resonance imaging and cognitive assessments. Voxel-based morphometry analysis used SPM8 with a substantia innominata brain mask to define the subspace for voxel GM analyses. Group differences, and selected behavioural and clinical correlates, were assessed. RESULTS: Compared with that in controls, bilateral GM loss in the substantia innominata was apparent in both AD and DLB. Relative to controls, significant bilateral GM loss in the substantia innominata was observed in DLB and AD. In DLB, significant associations were also observed between substantia innominata GM volume loss, and the levels of cognitive impairment and severity of cognitive fluctuations. CONCLUSIONS: Relative to that controls, atrophy of the substantia innominata was apparent in DLB and AD, and is associated with specific clinical manifestations in DLB. (c) 2016 The Authors. International Journal of Geriatric Psychiatry Published by John Wiley & Sons Ltd. PMID- 27197958 TI - Large-scale multiplex absolute protein quantification of drug-metabolizing enzymes and transporters in human intestine, liver, and kidney microsomes by SWATH-MS: Comparison with MRM/SRM and HR-MRM/PRM. AB - The purpose of the present study was to examine simultaneously the absolute protein amounts of 152 membrane and membrane-associated proteins, including 30 metabolizing enzymes and 107 transporters, in pooled microsomal fractions of human liver, kidney, and intestine by means of SWATH-MS with stable isotope labeled internal standard peptides, and to compare the results with those obtained by MRM/SRM and high resolution (HR)-MRM/PRM. The protein expression levels of 27 metabolizing enzymes, 54 transporters, and six other membrane proteins were quantitated by SWATH-MS; other targets were below the lower limits of quantitation. Most of the values determined by SWATH-MS differed by less than 50% from those obtained by MRM/SRM or HR-MRM/PRM. Various metabolizing enzymes were expressed in liver microsomes more abundantly than in other microsomes. Ten, 13, and eight transporters listed as important for drugs by International Transporter Consortium were quantified in liver, kidney, and intestinal microsomes, respectively. Our results indicate that SWATH-MS enables large-scale multiplex absolute protein quantification while retaining similar quantitative capability to MRM/SRM or HR-MRM/PRM. SWATH-MS is expected to be useful methodology in the context of drug development for elucidating the molecular mechanisms of drug absorption, metabolism, and excretion in the human body based on protein profile information. PMID- 27197957 TI - The effect of siblings and family dog ownership on children's independent mobility to neighbourhood destinations. AB - OBJECTIVE: To investigate the effect of sibling age, gender and dog ownership on children's independent mobility and how this varies according to the destination visited. METHODS: Parents reported whether their child had an older sibling; if the child and older sibling were of the same gender; the number of older siblings; if they owned a dog; and whether their child was allowed to independently travel to school, friends' or family house, park/oval/sporting field and local shop. Data were analysed for 181 children aged 8-15 years. RESULTS: The strongest significant sibling effect for independently mobility to school, local shop and >=3 destinations was for having an older sibling of the same gender (p<=0.05). For independent mobility to a friend's house and park, the strongest significant sibling effect was for having one older sibling (p<=0.05). Dog ownership was associated with increased odds of being independently mobile to >=3 destinations (OR=2.43; 95%CI=1.03-5.74). CONCLUSIONS: Parents may be more likely to grant children licence to travel to local places if they are accompanied by an older sibling or the family dog. IMPLICATIONS: Understanding the effects of siblings and dog ownership on children's independent mobility will assist in identifying strategies through which independent mobility can be encouraged. PMID- 27197960 TI - Association between variants in nicotinic acetylcholine receptor genes and smoking cessation in a Chinese rural population. AB - BACKGROUND AND OBJECTIVES: Genetic studies have revealed a significant association between variants in nicotinic acetylcholine receptor (CHRN) genes and smoking cessation, but the results are inconsistent. In this study, we aimed to examine the relationship between single nucleotide polymorphisms (SNPs) in seven CHRN genes and smoking cessation in a Chinese rural population. METHODS: Participants were recruited from 17 villages of 3 counties in Shandong, China. DNA was extracted from the blood samples. Thirty-two SNPs in seven CHRN genes were genotyped. Logistic regression was used to explore the relationship between single SNP and smoking cessation. Pearson's chi(2) test was performed to test the association between haplotype and smoking cessation. RESULTS: Rs578776 (in CHRNA3), rs660652 (in CHRNA3), and rs588765 (in CHRNA5) were significantly related to smoking cessation. Two haplotypes were associated with smoking cessation. CONCLUSIONS: This study confirmed the association between CHRN genes and smoking cessation in the Chinese rural population. SCIENTIFIC SIGNIFICANCE: Our findings provide confirmatory support to the role of CHRN genes to the etiology of smoking cessation in the Chinese rural population. (Am J Addict 2016;25:297-300). PMID- 27197959 TI - The Effect of Chronic Kidney Disease on Mortality with Cardiac Resynchronization Therapy. AB - BACKGROUND: Cardiac resynchronization therapy (CRT) improves functional status, reduces heart failure hospitalizations, and decreases mortality. Several comorbidities including renal function affect outcomes with CRT. However, moderate to severe chronic kidney disease (CKD) was an exclusion criterion in the large randomized control trials. OBJECTIVE: To evaluate the association of renal function on survival following CRT implantation. METHODS: This was a retrospective analysis of 432 consecutive patients implanted with an implantable cardioverter defibrillator with CRT (CRT-D). The primary end point was defined as death by any cause, and it was determined using hospital records and the U.S. Social Security Death Index. A Kaplan-Meier analysis was performed separating renal dysfunction into renal stage based on glomerular filtration rate. Multivariate analysis was performed to assess the clinical predictors of mortality. RESULTS: Patients were followed for up to 12 years with a mean follow up time of 4.3 +/- 3.2 years. A total of 164 patients (39.3%) died over the course of the study. Patients with normal and mild renal diseases (Stages 1 and 2) had improved survival compared with those with moderate-, severe-, or end stage (Stages 3-5) renal disease. This effect remained statistically significant after multivariate analysis. The estimated 5-year mortality was 36.3% for stage 1, 33.4% for stage 2, 40.6% for stage 3, and 62.1% for stage 4/5 kidney disease (P = 0.004 by log-rank test). CONCLUSION: CKD is a strong and an independent predictor of long-term mortality among patients undergoing CRT-D implantation. PMID- 27197961 TI - Low thrombin generation during major orthopaedic surgery fails to predict the bleeding risk in inhibitor patients treated with bypassing agents. AB - INTRODUCTION: In the presence of high-titre inhibitors, haemostatic bypassing agents are used to control bleeding and perform surgery. In this setting, no specific laboratory test is yet available to guide drug choice, monitor treatment efficacy and predict the risk of bleeding. AIM: The aims of this study, carried out in patients candidate to orthopaedic surgery, were to assess the dose dependent increase in thrombin generation (TG) after infusion of bypassing agents and to evaluate whether or not a correlation existed between the haemostatic efficacy of bypassing therapies and perioperative TG values. METHODS AND RESULTS: TG was measured in 16 inhibitor patients, 10 of whom underwent 11 major orthopaedic procedures. In the non-bleeding state, TG significantly improved 30 min after whichever dose (P < 0.01), with no dose-response relationship when values obtained after different rFVIIa doses were compared. TG significantly improved 30 min after the preoperative bolus (P < 0.05), while during the postoperative period TG values measured before and after dosing did not differ. Moreover, postoperative TG values were similar or even more impaired (P <= 0.05) than those measured before preoperative dosing. No difference was found by comparing procedures with and without bleeding complications and yet no bleeding occurred in spite of persistently low TG values in one-third of procedures. CONCLUSION: This study fails to support a definite role for the TG assay as a reliable laboratory tool to monitor the haemostatic efficacy of bypassing therapies and as a predictor of the risk of bleeding in inhibitor patients using these agents during orthopaedic surgery. PMID- 27197962 TI - Outcome of Jehovah's Witnesses after adult cardiac surgery: systematic review and meta-analysis of comparative studies. AB - BACKGROUND: The objective was to evaluate the early outcome after adult cardiac surgery in Jehovah's Witnesses (JWs) compared with controls not refusing blood transfusions. STUDY DESIGN AND METHODS: A literature review was performed through PubMed, Scopus, and Google Scholar to identify any comparative study evaluating the outcome of JWs and patients not refusing blood transfusion after adult cardiac surgery. RESULTS: Six studies comparing the outcome of 564 JWs and 903 controls fulfilled the inclusion criteria of this study. All series included a matched control cohort. Baseline characteristics of these two cohorts were similar, but JWs had higher hemoglobin (Hb) levels as reported in three studies. Pooled analysis of postoperative outcomes showed that JWs had higher postoperative levels of Hb (data from four studies: mean, 11.5 g/L vs. 9.8 g/L; p < 0.001) and significantly less postoperative blood loss (mean, 402 mL vs. 826 mL; p < 0.001) compared to controls. JWs and controls had similar early outcome. However, JWs had a nonsignificant trend toward decreased early mortality (2.6% vs. 3.6%; p = 0.318), reoperation for bleeding (3.2% vs. 4.7%; p = 0.070), atrial fibrillation (9.9% vs. 14.3%; p = 0.056), stroke (2.2% vs. 3.1%; p = 0.439), myocardial infarction (0.4% vs. 1.4%; p = 0.203), and length of stay in the intensive care unit (1.5 days vs. 2.0 days; p = 0.081). CONCLUSION: JWs undergoing adult cardiac surgery have a nonsignificant trend toward better early outcome than controls receiving or not blood transfusions. The suboptimal quality of available studies prevents conclusive results on the possible benefits of a transfusion-free strategy in patients not refusing blood transfusion. PMID- 27197963 TI - Anisotropic Slippery Surfaces: Electric-Driven Smart Control of a Drop's Slide. AB - Anisotropic slippery surfaces composed of directional, porous, conductive poly(3 hexylthiophene) (P3HT) fibers, and silicone oil exhibit excellent anisotropic sliding properties for several liquid droplets and the reversible control of conductive liquid droplets sliding on these surfaces under the application of voltage. PMID- 27197964 TI - Introductory paragraph. PMID- 27197966 TI - Highly variable sensitivity of five binding and two bio-assays for TSH-receptor antibodies. AB - PURPOSE: TSH-receptor (TSHR) antibodies (Ab) can be measured with binding or bio assays. Sensitivity and specificity of five binding and two bio-assays were compared. METHODS: TSHR-blocking (TBAb) and TSHR-stimulating (TSAb) Ab were measured with reporter bio-assays. Blocking activity was defined as percent inhibition of luciferase expression relative to induction with bTSH alone. TSAb was reported as percentage of specimen-to-reference ratio (SRR%). TSHR-binding inhibitory immunoglobulins (TBII) were measured with Kronus, Dynex, Kryptor, Cobas, and Immulite. RESULTS: Sixty patients with Graves' disease (GD), 20 with Hashimoto's thyroiditis (HT), and 20 healthy controls (C) were included. C tested negative in all assays (specificity 100 %) while all 60 hyperthyroid GD patients tested positive in the TSAb bio-assay (sensitivity 100 %). Among these 60 GD patients, 20 had low TSAb positivity (SRR% 140-279), but were TBII positive in only 20 (100 %), 7 (35 %), 9 (45 %), 11 (55 %), and 18 (90 %) using the Kronus, Dynex, Kryptor, Cobas, and Immulite, respectively. In 20 moderate TSAb-positive (SRR% 280-420) patients, TBII tested positive in 20 (100 %), 14 (70 %), 13 (65 %), 16 (80 %), and 19 (95 %), respectively. The high (SRR% > 420) TSAb-positive patients were all TBII positive. All 20 hypothyroid HT patients tested TBAb positive (sensitivity 100 %) in the bio-assay while they tested TBII positive in 20 (100 %), 18 (90 %), 20, 20, and 18, respectively. Results obtained with two luminometers correlated for TSAb positive (r = 0.99, p < 0.001), TBAb positive (r = 0.88, p < 0.001), and C (r = 0.86, p < 0.001). None of the binding assays differentiated between TSAb and TBAb. CONCLUSIONS: Sensitivity is highly variable between binding and bio-assays for TSHR-Abs. PMID- 27197965 TI - Adding genetic risk score to family history identifies twice as many high-risk men for prostate cancer: Results from the prostate cancer prevention trial. AB - BACKGROUND: While family history (FH) has been widely used to provide risk information, it captures only a small proportion of subjects with higher genetic susceptibility. Our objective is to assess whether a genetic risk score (GRS) calculated from prostate cancer (PCa) risk-associated single nucleotide polymorphisms (SNPs) can supplement FH for more effective risk stratification for PCa screening decision-making. METHODS: A GRS was calculated based on 29 PCa risk associated SNPs for 4,528 men of European descent in the placebo arm of the Prostate Cancer Prevention Trial (PCPT). At study entry, participants were free of PCa diagnosis. Performance of FH and GRS were measured by observed detection rate of PCa and high-grade PCa (Gleason score >=7) during the 7-year study. RESULTS: GRS was a significant predictor of PCa in men with or without a positive FH (P = 1.18 * 10(-4) and P = 4.50 * 10(-16) , respectively). Using FH alone, as expected, the 17% of men who were FH+ had a PCa detection rate that was significantly higher (29.02%) than FH- men (23.43%, P = 0.001). When both FH+ or GRS >1.4 are considered, more than twice as many men (36%) can be classified as higher risk, as evidenced by a significantly higher PCa detection rate (30.98%) than in the remaining men (20.61%, P = 5.30 * 10(-15) ). If targeting only FH+ men, four out of five PCa cases would go undetected, as would a similarly large fraction (~80%) of high-grade PCa cases. In comparison, if targeting FH+ or GRS >1.4 men, almost half of all PCa cases would be detected, including 45% of high grade PCa cases. CONCLUSIONS: A prostate cancer GRS can supplement family history to better identify higher risk men for targeted intervention. Prostate 76:1120 1129, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27197968 TI - Short follow-up evaluation of proximal femoral varus osteotomy for treatment of Legg-Calve-Perthes disease. AB - BACKGROUND: There are many methods of treating Legg-Calve-Perthes disease, including operative and nonoperative methods. Femoral varus osteotomy is one of the surgical methods used to treat this disease, and it involves changing the alignment of the proximal femur to improve containment of the femoral epiphysis in the acetabulum. The aims of this study were to evaluate the results of femoral varus osteotomy for the treatment of Perthes disease according to various classification and grading schemes, as well as to compare the results to those obtained using other methods of treatment reported in the literature. MATERIALS AND METHODS: Twenty-three patients with Legg-Calve-Perthes disease were treated using a proximal femoral varus osteotomy procedure. The mean age of the patients was 7.8 years (range: 6-11.5 years). The average follow-up was 36.2 months (range: 29-48 months). RESULTS: The patients were classified and graded according to the Catterall and Herring classifications. The preoperative and postoperative mean epiphyseal extrusion indices were as follows: group III (B), 10.88 % and 7.22 %, P = 0.027; group III (BC), 15.81 and 8.93 %, P = 0.005; group IV (C), 72.64 and 39.44 %, P = 0.018. The preoperative and the postoperative mean Wiberg's CE angle were as follows: group III (B), 26.88 degrees and 37.81 degrees , P = 0.028; group III (BC), 24.4 degrees and 32.2 degrees , P = 0.005; group IV (C), 20.89 degrees and 28.41 degrees , P = 0.018. Changes in Iowa clinical hip scores were as follows: group III (B), 54.8 to 92.33, P = 0.027; group III (BC), 47.3 to 87.8, P = 0.005; group IV (C) 34.43 to 68.29, P = 0.017. In the last follow-up, the mean limb length discrepancy after plate removal was 0.9 cm (range: 0.0-2 cm) of shortening on the operated side. The author of the present study did not see any progressive change in this parameter during the follow-up period, especially after hardware removal and in the younger boys. All of the osteotomies united within 3 months without loss of fixation. CONCLUSION: According to the results of the present study, proximal femoral varus osteotomy gives good results in children between the ages of 6 and 10 years without any femoral head deformity and flattening, especially with good containment in abduction. LEVEL OF EVIDENCE: Level IV. PMID- 27197967 TI - Regulatory mechanisms of microRNA expression. AB - MicroRNAs (miRs, miRNAs) are small molecules of 18-22 nucleotides that serve as important regulators of gene expression at the post-transcriptional level. One of the mechanisms through which miRNAs regulate gene expression involves the interaction of their "seed" sequences primarily with 3'-end and more rarely with 5'-end, of mRNA transcribed from target genes. Numerous studies over the past decade have been devoted to quantitative and qualitative assessment of miRNAs expression and have shown remarkable changes in miRNA expression profiles in various diseases. Thus, profiling of miRNA expression can be an important tool for diagnostics and treatment of disease. However, less attention has been paid towards understanding the underlying reasons for changes in miRNA expression, especially in cancer cells. The purpose of this review is to analyze and systematize current data that explains reasons for changes in the expression of miRNAs. The review will cover both transcriptional (changes in gene expression and promoter hypermethylation) and post-transcriptional (changes in miRNA processing) mechanisms of regulation of miRNA expression, as well as effects of endogenous (hormones, cytokines) and exogenous (xenobiotics) compounds on the miRNA expression. The review will summarize the complex multilevel regulation of miRNA expression, in relation to cell type, physiological state of the body and various external factors. PMID- 27197969 TI - Arterial-ventricular and interventricular interaction in isolated post-capillary and combined pulmonary hypertension in severe mitral stenosis. AB - BACKGROUND: Isolated post-capillary pulmonary hypertension (Ipc-PH) is characterized by elevated left atrial pressures that are passively transmitted upstream, whereas combined pre- and post-capillary PH (Cpc-PH) demonstrates additional reactive changes in pulmonary vasculature. The increased load imposed on the right ventricle (RV) influences left ventricular (LV) mechanics by means of interventricular interaction. However, there is lack of evidence to substantiate the effect of possible additional alterations in the arterio ventricular (AV) coupling and their effect on LV function. Considering the discrepant RV load in Cpc-PH and Ipc-PH, we sought to investigate whether these two conditions are also characterized by differential alterations in AV coupling. METHODS AND RESULTS: Invasive hemodynamic and echocardiographic data of 120 patients with PH due to severe rheumatic mitral stenosis before and immediately after percutaneous valvulotomy, along with 40 age-matched healthy controls, were analyzed. Effective arterial (E a) and ventricular elastance (E es) were measured. PH patients demonstrated elevated LV afterload (E a) along with AV uncoupling, and these derangements were more evident in the Cpc-PH group [E a: 3.3 (2.3-5.4) vs 2.6 (2.1-3.5) mmHg/mL, E a/E es: 0.73 (0.6-0.9) vs 0.88 (0.7 1.2), p < 0.05]. In addition, PH was associated with reduced LV deformation, which was mainly determined by elevated E a, while the effect of interventricular interaction was limited to the septal wall. CONCLUSIONS: Our results suggest that in addition to the interventricular interaction, an abnormal AV coupling contributes to the altered LV mechanics that has been associated with adverse prognosis in Cpc-PH. PMID- 27197970 TI - Adaptation and validation of the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) for the Netherlands. AB - BACKGROUND: The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) is the first disease-specific instrument for pulmonary arterial hypertension (PAH) to assess patient-perceived symptoms, activity limitations and quality of life. To be able to use this questionnaire in the Netherlands, the aim of the study was to translate and validate this instrument for the Dutch-speaking population. METHODS: First the CAMPHOR was translated into Dutch (by means of a bilingual and a lay panel) and field-tested by means of cognitive debriefing interviews with ten PAH patients. For psychometric evaluation, 80 patients with PAH or chronic thromboembolic pulmonary hypertension (CTEPH) were asked to complete the CAMPHOR twice over a two-week period. To test for construct validity, participants also completed the Nottingham Health Profile (NHP). RESULTS: The Dutch version of the CAMPHOR showed high internal consistency for all scales (Cronbach's alpha 0.89 0.91) and excellent reproducibility over two weeks (reliability coefficients 0.87 0.91). Concurrent validity showed that the CAMPHOR scales correlated as expected with the NHP scales. The CAMPHOR was able to distinguish between patient groups based on self-reported general health status, disease severity and NYHA classification demonstrating evidence of known group validity. The CAMPHOR activity limitations scale correlated moderately with the distance walked during the 6-minute walk test (r = -0.47, p < 0.01) and the symptoms scale with the Borg dyspnoea score (r = 0.51, p < 0.01). CONCLUSION: The Dutch version of the CAMPHOR is a reliable and valid measure of quality of life and health status in patients with PAH and CTEPH is recommended for use in routine care and in clinical research. PMID- 27197971 TI - Secondhand Smoke Exposure and Smoke-Free Policy Support Among Public Housing Authority Residents in Rural and Tribal Settings. AB - Previous research has shown that multi-unit housing (MUH) residents are at risk of secondhand smoke (SHS) exposure, which can transfer between units. The purpose of this study was to determine SHS exposure and examine attitudes towards smoking policies among public housing authority (PHA) residents in rural and tribal settings. A self-administered questionnaire was completed by 895 adult tenants (41 % response rate) living in PHA multiunit buildings in Montana in 2013. Our primary outcome was tenant support of smoke-free policies; our secondary outcome was exacerbation of child asthma symptoms due to SHS exposure. In 2014, we used multiple logistic regression models to test associations between independent variables and outcomes of interest. The majority (80.6 %) of respondents supported having a smoke-free policy in their building, with support being significantly higher among nonsmokers [adjusted odds ratio (aOR) 4.2, 95 % confidence interval (CI) 1.5-11.6] and among residents living with children (aOR 2.9, 95 % CI 1.3-6.2). Tribal residents were as likely to support smoke-free policies as non-tribal residents (aOR 1.4; 95 % CI 0.5-4.0). Over half (56.5 %) of respondents reported SHS exposure in their home; residents in a building with no smoke-free policy in place were significantly more likely to report exposure (aOR 3.5, 95 % CI 2.2-5.5). SHS exposure was not significantly associated with asthma symptoms. There is a significant reduction in exposure to SHS in facilities with smoke-free policies and there is strong support for such policies by both tribal and non-tribal MUH residents. Opportunities exist for smoke-free policy initiatives in rural and tribal settings. PMID- 27197972 TI - The electrolarynx as a communication tool for mechanically ventilated critically ill patients: a prospective feasibility study. PMID- 27197973 TI - Hospital Readmissions in a Community-based Sample of Homeless Adults: a Matched cohort Study. AB - BACKGROUND: Hospital readmission rates are a widely used quality indicator that may be elevated in disadvantaged populations. OBJECTIVE: The objective of this study was to compare the hospital readmission rate among individuals experiencing homelessness with that of a low-income matched control group, and to identify risk factors associated with readmission within the group experiencing homelessness. DESIGN: We conducted a 1:1 matched cohort study comparing 30-day hospital readmission rates between homeless patients and low-income controls matched on age, sex and primary reason for admission. Multivariate analyses using generalized estimating equations were used to assess risk factors associated with 30-day readmission in the homeless cohort. PARTICIPANTS: This study examined a cohort of 1,165 homeless adults recruited at homeless shelters and meal programs in Toronto, Ontario, between 6 December 2004 and 20 December 2005. MAIN MEASURES: The primary outcome was the occurrence of an unplanned medical or surgical readmission within 30 days of discharge from hospital. KEY RESULTS: Between 6 December 2004 and 31 March 2009, homeless participants (N = 203) had 478 hospitalizations and a 30-day readmission rate of 22.2 %, compared to 300 hospitalizations and a readmission rate of 7.0 % among matched controls (OR = 3.79, 95 % CI 1.93-7.39). In the homeless cohort, having a primary care physician (OR = 2.65, 95 % CI 1.05-6.73) and leaving against medical advice (OR = 1.96, 95 % CI 0.99-3.86) were associated with an increased risk of 30-day readmission. CONCLUSIONS: Homeless patients had nearly four times the odds of being readmitted within 30-days as compared to low-income controls matched on age, sex and primary reason for admission to hospital. Further research is needed to evaluate interventions to reduce readmissions among this patient population. PMID- 27197976 TI - Income Inequality and Child Mortality in Wealthy Nations. AB - This chapter presents evidence of a relationship between child mortality data and socio-economic factors in relatively wealthy nations. The original study on child mortality that is reported here, which first appeared in a UK medical journal, was undertaken in a school of business by academics with accounting and finance backgrounds. The rationale explaining why academics from such disciplines were drawn to investigate these issues is given in the first part of the chapter. The findings related to child mortality data were identified as a special case of a wide range of social and health indicators that are systematically related to the different organisational approaches of capitalist societies. In particular, the so-called Anglo-American countries show consistently poor outcomes over a number of indicators, including child mortality. Considerable evidence has been adduced in the literature to show the importance of income inequality as an explanation for such findings. An important part of the chapter is the overview of a relatively recent publication in the epidemiological literature entitled The Spirit Level: Why Equality Is Better for Everyone, which was written by Wilkinson and Pickett. PMID- 27197975 TI - A Cross-Sectional Assessment of the Quality of Physician Quality Reporting System Measures. AB - BACKGROUND: Starting in 2015, the Center for Medicare and Medicaid Services (CMS) requires all Medicare providers to report quality measures through Physician Quality Reporting System (PQRS) or incur a 1.5 % financial penalty. Research indicates that physicians believe this reporting does not lead to high quality care; however, little research has examined what PQRS actually measures, which is reflective of the physicians and patient disease populations being assessed. OBJECTIVES: (1) Identify the proportion of measures that apply to different medical specialties, types of quality measurement, and National Quality Strategy (NQS) priorities. (2) Identify how different specialties are required to measure quality and NQS priorities. (3) Compare the 2011 and 2015 measures. DESIGN AND MAIN MEASURES: This was a categorical qualitative analysis of 2011 and 2015 PQRS measures. One hundred and ninety-eight and 254 individual measures, respectively, were analyzed by three domains: medical specialty measured, type of measure, and NQS priority category. KEY RESULTS: Between 2011 and 2015, the type of measures changed significantly, with fewer processes (85.4 % vs. 66.5 %, p < 0.001) and more outcomes (12.6 % vs. 29.1 %, p < 0.001). The measures showed no significant specialty or NQS category differences. For subcategories within each specialty in 2015, differences in measure type were statistically significant: surgery had the highest percentage of outcomes (61.1 %) compared to 21.7 % of internal medicine and 5.9 % of obstetrics/gynecology. For NQS categories, internal medicine had the highest percentage of effective clinical care measures (68.5 %), compared to 22.2 % in surgery. Surgery had the highest percentage of patient safety (31.9 %) and communication and care coordination measures (27.8 %) compared with internal medicine (5.4 % and 6.5 %). CONCLUSIONS: Our study shows that PQRS measures include many medical specialties and significantly more outcomes in recent years, particularly for surgery. PQRS still lacks sufficient measures for half of NQS priorities and sufficient outcomes to assess internal medicine and obstetrics/gynecology. CMS must continue to improve PQRS measures to better assess and encourage high-quality care for all Americans. PMID- 27197974 TI - Assessing Problematic Substance Use in HIV Care: Which Questions Elicit Accurate Patient Disclosures? AB - BACKGROUND: Substance use is associated with higher rates of antiretroviral non adherence and poor HIV outcomes. This study examined how HIV care providers assess substance use, and which questions elicit accurate patient disclosures. METHODS: We conducted a conversation analysis of audio-recorded encounters between 56 providers and 162 patients living with HIV (PLWH) reporting active substance use in post-encounter interviews (cocaine or heroin use in the past 30 days, > 4 days intoxicated in past 30 days, or AUDIT score >= 8). We assessed the frequency of substance use discussion, characterized the types of questions used by providers, and determined the frequency of accurate patient disclosure by question type. RESULTS: In 55 reports of active substance use, providers already knew about the use (n = 16) or patients disclosed unpromptednn = 39). Among the remaining 155 instances of substance use in which providers had the opportunity to elicit disclosure, 78 reports (50 %) of substance use were not discussed. Of the remaining 77 reports in which the provider asked about substance use, 55 (71 %) patients disclosed and 22 (29 %) did not disclose. Questions were classified as: open-ended (n = 18, "How's the drinking going?"); normalizing (n = 14, "When was the last time you used?"); closed-ended (n = 36, "Have you used any cocaine?"); leading towards non-use (n = 9, "Have you been clean?"). Accurate disclosure followed 100 % of open-ended and normalizing questions, 58 % of closed ended questions, and 22 % of leading questions. After adjusting for drug type, closed-ended questions were 41 % less likely (p < 0.001), and 'leading' questions 78 % less likely (p = 0.016) than broad and normalizing questions to elicit disclosures. CONCLUSION: Providers in this sample missed almost half of the opportunities to identify and discuss substance use with PLWH. Providers can increase the probability of patient disclosure by using open-ended or normalizing questions that ask about the "last time" that the patient used drugs or alcohol. PMID- 27197977 TI - Hyperbaric Oxygen Intervention Modulates Early Brain Injury after Experimental Subarachnoid Hemorrhage in Rats: Possible Involvement of TLR4/NF-x03BA; B Mediated Signaling Pathway. AB - BACKGROUND/AIMS: Previous studies have proved that the activation of TLR4/NF x03BA; B signaling pathway is involved in inflammatory processes in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Hyperbaric oxygen (HBO) intervention has successfully been used to treat several animal models of tissue injury via its anti-inflammation property. This study was undertaken to investigate the influence of HBO administration on the TLR4/NF-x03BA; B signaling pathway in rats at the early stage of SAH. METHODS: Male Sprague-Dawley rats (n = 150) were randomly divided into 5 groups: the sham, the sham + 2.8 atmospheres absolute (ATA) HBO group, the SAH group, the SAH + 2.0ATA HBO group, the SAH + 2.8ATA HBO group. Each group (n = 30) was randomly subdivided into three subgroups that were examined at the following time points: 24 h, 48 h and 72 h post-injury. HBO (100% O2, 2.0ATA or 2.8ATA for 90mins) was initiated 12 h after injury. Neurological deficit, brain edema and blood-brain barrier (BBB) permeability were assessed to evaluate the development of EBI. The expressions of TLR4, NF-x03BA; B and pro-inflammatory cytokines in the cortical were determined by real time polymerase chain reaction (RT-PCR), western blot, immunohistochemistry, or enzyme-linked immunosorbent assay (ELISA). RESULTS: Our study showed that treatment with HBO significantly decreased the expressions of TLR4, NF-x03BA; B and the downstream inflammatory agents, such as TNF-alpha, IL 6, IL-1beta and ICAM-1, and also improved brain edema, blood-brain barrier permeability and neurologic function. CONCLUSIONS: These findings indicate that HBO treatment may result in abatement of the development of EBI after SAH, possibly through suppression of TLR4/NF-x03BA; B signaling pathway. PMID- 27197978 TI - Behavioral Change Strategies for Improving Complementary Feeding and Breastfeeding. AB - Improving infant and young child feeding (IYCF) practices, including breastfeeding and complementary feeding, has been identified as one of the most effective interventions to improve child survival, stunting and wasting. Evidence from randomized controlled trials suggests that effective promotion of breastfeeding and complementary feeding, with or without food provision, has the potential to improve IYCF practices and child nutrition. However, in many countries, breastfeeding practices and complementary feeding practices are still far from optimal. The lack of implementation of available, effective, affordable interventions in scale-up programs is in part attributed to a lack of innovative, creative and effective behavioral change strategies that enable and encourage caregivers. Successful behavioral change strategies should be based on a rigorous situational analysis and formative research, and the findings and insights of formative research should be used to further design interventions that address the identified barriers and enablers, to select delivery channels, and to formulate appropriate and effective messages. In addition, successful behavioral change interventions should a priori define and investigate the program impact pathway to target behavioral change and should assess intermediary behavioral changes and indicators to learn why the expected outcome was achieved or not achieved by testing the program theory. The design of behavioral change communication must be flexible and responsive to shifts in societies and contexts. Performance of adequate IYCF also requires investments to generate community demand through social mobilization, relevant media and existing support systems. Applying these principles has been shown to be effective in improving IYCF practices in Vietnam, Bangladesh and Ethiopia and is recommended to be adopted by other programs and countries in order to accelerate progress in improving child nutrition. PMID- 27197979 TI - Combining Stress Exposure and Stress Generation: Does Neuroticism Alter the Dynamic Interplay of Stress, Depression, and Anxiety Following Job Loss? AB - OBJECTIVE: Emerging models of stress point to a dynamic formulation where stressors and internalizing symptoms reciprocally influence each other. This study tested whether this dynamic interplay is the result of a general internalizing process underlying both depression and anxiety, and whether it varies with neuroticism. METHOD: A total of 426 adults (51% female; 47% White, 42% African American) were assessed five times over 6 months following loss of employment, using repeated measurements of stressors, depression, anxiety, and neuroticism. RESULTS: Latent growth across 6 months and multilevel cross-lagged regressions across 6 weeks supported the hypothesis that stressors and internalizing symptoms have reciprocal effects after job loss. Findings for unique variation in depression paralleled those for general internalizing, whereas few findings emerged for general or social anxiety after controlling for internalizing. Neuroticism strengthened the association of change in stressors with change in symptoms across 6 months. Those with high neuroticism showed less reduction in internalizing following reemployment and were less likely to be reemployed when starting with higher internalizing. CONCLUSIONS: The moderated reciprocal effects model helps account for onset, maintenance, and resolution of symptoms following job loss. We speculate that these findings may be due in part to differential emotion regulation and reductions in motivation. PMID- 27197980 TI - Paroxetine use during pregnancy and the risk of cardiac defects. PMID- 27197981 TI - Nephrology education for medical students: a narrative review. AB - BACKGROUND: Strategies used to teach nephrology to medical students are not well studied. This study assesses the published literature on medical student education in nephrology. METHODS: A review of the published literature on nephrology education for medical students was conducted on two major online search engines (PubMed and ERIC). In addition, references of the manuscripts discovered in these searches were reviewed. The empirical studies were categorized by subject within nephrology and research design. RESULTS: We found 26 original studies in which a method of teaching nephrology to medical students was described. The studies dated from 1977 to 2015. The focus of these nephrology teaching experiences was as follows: anatomy (6.5%), physiology (22.6%), pathophysiology (29.0%), pathology (6.5%), treatment (25.8%), and general nephrology (9.7%). The studies were also categorized into various types of research design. 6.9% had either no assessment of the educational experience or had a description too vague to categorize it; 3.4% involved a survey about the existing educational approach before a curriculum change was implemented; 55.2% used surveys or tests after an educational course was carried out; 10.3% sought feedback from students before and after the educational experience; 13.8% were case studies; and 10.3% included a randomized controlled trial. The randomized controlled trials involved teaching techniques focused on the pathophysiology of renal disease. CONCLUSIONS: Rigor was lacking in most empirical studies on medical student education in nephrology. Well-designed randomized controlled studies are needed to accurately assess the effectiveness of the educational techniques introduced into medical school curricula. PMID- 27197982 TI - Human Senataxin Modulates Structural Plasticity of the Neuromuscular Junction in Drosophila through a Neuronally Conserved TGFbeta Signalling Pathway. AB - BACKGROUND: Mutations in the human Senataxin (hSETX) gene have been shown to cause two forms of neurodegenerative disorders - a dominant form called amyotrophic lateral sclerosis type 4 (ALS4) and a recessive form called ataxia with oculomotor apraxia type 2 (AOA2). SETX is a putative DNA/RNA helicase involved in RNA metabolism. Although several dominant mutations linked with ALS4 have been identified in SETX, their contribution towards ALS4 pathophysiology is still elusive. METHOD: In order to model ALS4 in Drosophila and to elucidate the morphological, physiological and signalling consequences, we overexpressed the wild-type and pathological forms of hSETX in Drosophila. RESULTS AND CONCLUSIONS: The pan-neuronal expression of wild-type or mutant forms of hSETX induced morphological plasticity at neuromuscular junction (NMJ) synapses. Surprisingly, we found that while the NMJ synapses were increased in number, the neuronal function was normal. Analysis of signalling pathways revealed that hSETX modulates the Highwire (Hiw; a conserved neuronal E3 ubiquitin ligase)-dependent bone morphogenetic protein/TGFbeta pathway. Thus, our study could pave the way for a better understanding of ALS4 progression by SETX through the regulation of neuronal E3 ubiquitin pathways. PMID- 27197983 TI - Plain radiography of the skull after investigation for raised calcium. PMID- 27197984 TI - Rotenone Analysis by Liquid Chromatography-Tandem Mass Spectrometry with Information-Dependent Acquisition in a Fatal Case of Rotenone Poisoning with a Commercial Organic Insecticide Being Sold in Korea. AB - Rotenone is a neurotoxin derived from Derris roots or yam bean of genus Derris or Lonchocarpus It is known to cause Parkinson-like symptoms and is a potent electron transport inhibitor. Rotenone was detected in postmortem specimens in a fatal case of rotenone poisoning with an organic pesticide by liquid chromatography-tandem mass spectrometry with an information-dependent acquisition and MS-MS library search. The forensic specimens were prepared by solid-phase extraction with a Bond Elut((r)) Certify cartridge. The mobile phase comprised 5 mM ammonium formate in 10% methanol and 5 mM ammonium formate in 90% methanol. The assay was linear over the range from 0.01 to 1.0 mg/L (r(2) = 0.995). The limit of detection and quantitation in the blood were 0.001 mg/L (signal-to noise, S/N = 3) and 0.003 mg/L (S/N = 10), respectively. The intraday accuracy and precision for rotenone that were determined by five replicates at 0.02, 0.10 and 1.0 mg/L in blood were <15.0% of bias and <9.0% of CV, respectively. The interday accuracy and precision for rotenone that were determined by seven replicates at 0.02, 0.10 and 1.0 mg/L in blood were <18.0% of bias and <17.0% of CV, respectively. Relative recovery with 0.02, 0.1 and 1.0 mg/L in blood was 104.2, 103.3 and 81.6% (n = 6), respectively. The described method was applied for the determination of rotenone in a fatal case of intoxication of a 33-year old man who was found dead on a bed in a temporary house. In this case study, the concentrations of rotenone in heart blood (HB), peripheral blood (PB), gastric contents and vitreous humor were 0.77 mg/L, 0.02 mg/L, 126.4 mg/kg and 0.003 mg/L, respectively. The rotenone concentration ratio of the HB/PB was 38.8 and that of gastric contents/PB was 6412.3, suggesting a massive ingestion of rotenone with postmortem redistribution. This study is the report of rotenone detection in a fatal case with the ingestion of the organic insecticide containing rotenone. PMID- 27197986 TI - Computational Modeling of Venous Sinus Stenosis in Idiopathic Intracranial Hypertension. AB - BACKGROUND AND PURPOSE: Idiopathic intracranial hypertension has been associated with dural venous sinus stenosis in some patients, but the hemodynamic environment of the dural venous sinuses has not been quantitatively described. Here, we present the first such computational fluid dynamics model by using patient-specific blood pressure measurements. MATERIALS AND METHODS: Six patients with idiopathic intracranial hypertension and at least 1 stenosis or atresia at the transverse/sigmoid sinus junction underwent MR venography followed by cerebral venography and manometry throughout the dural venous sinuses. Patient specific computational fluid dynamics models were created by using MR venography anatomy, with venous pressure measurements as boundary conditions. Blood flow and wall shear stress were calculated for each patient. RESULTS: Computational models of the dural venous sinuses were successfully reconstructed in all 6 patients with patient-specific boundary conditions. Three patients demonstrated a pathologic pressure gradient (>=8 mm Hg) across 4 dural venous sinus stenoses. Small sample size precludes statistical comparisons, but average overall flow throughout the dural venous sinuses of patients with pathologic pressure gradients was higher than in those without them (1041.00 +/- 506.52 mL/min versus 358.00 +/- 190.95 mL/min). Wall shear stress was also higher across stenoses in patients with pathologic pressure gradients (37.66 +/- 48.39 Pa versus 7.02 +/- 13.60 Pa). CONCLUSIONS: The hemodynamic environment of the dural venous sinuses can be computationally modeled by using patient-specific anatomy and physiologic measurements in patients with idiopathic intracranial hypertension. There was substantially higher blood flow and wall shear stress in patients with pathologic pressure gradients. PMID- 27197985 TI - Effect of CTA Tube Current on Spot Sign Detection and Accuracy for Prediction of Intracerebral Hemorrhage Expansion. AB - BACKGROUND AND PURPOSE: Reduction of CT tube current is an effective strategy to minimize radiation load. However, tube current is also a major determinant of image quality. We investigated the impact of CTA tube current on spot sign detection and diagnostic performance for intracerebral hemorrhage expansion. MATERIALS AND METHODS: We retrospectively analyzed a prospectively collected cohort of consecutive patients with primary intracerebral hemorrhage from January 2001 to April 2015 who underwent CTA. The study population was divided into 2 groups according to the median CTA tube current level: low current (<350 mA) and high current (>=350 mA). CTA first-pass readings for spot sign presence were independently analyzed by 2 readers. Baseline and follow-up hematoma volumes were assessed by semiautomated computer-assisted volumetric analysis. Sensitivity, specificity, positive and negative predictive values, and accuracy of spot sign in predicting hematoma expansion were calculated. RESULTS: This study included 709 patients (288 and 421 in the low- and high-current groups, respectively). A higher proportion of low-current scans identified at least 1 spot sign (20.8% versus 14.7%, P = .034), but hematoma expansion frequency was similar in the 2 groups (18.4% versus 16.2%, P = .434). Sensitivity and positive and negative predictive values were not significantly different between the 2 groups. Conversely, high-current scans showed superior specificity (91% versus 84%, P = .015) and overall accuracy (84% versus 77%, P = .038). CONCLUSIONS: CTA obtained at high levels of tube current showed better diagnostic accuracy for prediction of hematoma expansion by using spot sign. These findings may have implications for future studies using the CTA spot sign to predict hematoma expansion for clinical trials. PMID- 27197987 TI - MRI Evaluation of Non-Necrotic T2-Hyperintense Foci in Pediatric Diffuse Intrinsic Pontine Glioma. AB - BACKGROUND AND PURPOSE: The conventional MR imaging appearance of diffuse intrinsic pontine glioma suggests intralesional histopathologic heterogeneity, and various distinct lesion components, including T2-hypointense foci, have been described. Here we report the prevalence, conventional MR imaging semiology, and advanced MR imaging features of non-necrotic T2-hyperintense foci in diffuse intrinsic pontine glioma. MATERIALS AND METHODS: Twenty-five patients with diffuse intrinsic pontine gliomas were included in this study. MR imaging was performed at 3T by using conventional and advanced MR imaging sequences. Perfusion (CBV), vascular permeability (ve, Ktrans), and diffusion (ADC) metrics were calculated and used to characterize non-necrotic T2-hyperintense foci in comparison with other lesion components, namely necrotic T2-hyperintense foci, T2 hypointense foci, peritumoral edema, and normal brain stem. Statistical analysis was performed by using Kruskal-Wallis and Wilcoxon rank sum tests. RESULTS: Sixteen non-necrotic T2-hyperintense foci were found in 12 tumors. In these foci, ADC values were significantly higher than those in either T2-hypointense foci (P = .002) or normal parenchyma (P = .0002), and relative CBV values were significantly lower than those in either T2-hypointense (P = .0002) or necrotic T2-hyperintense (P = .006) foci. Volume transfer coefficient values in T2 hyperintense foci were lower than those in T2-hypointense (P = .0005) or necrotic T2-hyperintense (P = .0348) foci. CONCLUSIONS: Non-necrotic T2-hyperintense foci are common, distinct lesion components within diffuse intrinsic pontine gliomas. Advanced MR imaging data suggest low cellularity and an early stage of angioneogenesis with leaky vessels resulting in expansion of the extracellular space. Because of the lack of biopsy validation, the underlying histoarchitectural and pathophysiologic changes remain unclear; therefore, these foci may correspond to a poorly understood biologic event in tumor evolution. PMID- 27197988 TI - Manual Segmentation of MS Cortical Lesions Using MRI: A Comparison of 3 MRI Reading Protocols. AB - BACKGROUND AND PURPOSE: Double inversion recovery has been suggested as the MR imaging contrast of choice for segmenting cortical lesions in patients with multiple sclerosis. In this study, we sought to determine the utility of double inversion recovery for cortical lesion identification by comparing 3 MR imaging reading protocols that combine different MR imaging contrasts. MATERIALS AND METHODS: Twenty-five patients with relapsing-remitting MS and 3 with secondary progressive MS were imaged with 3T MR imaging by using double inversion recovery, dual fast spin-echo proton-density/T2-weighted, 3D FLAIR, and 3D T1-weighted imaging sequences. Lesions affecting the cortex were manually segmented by using the following 3 MR imaging reading protocols: Protocol 1 (P1) used all available MR imaging contrasts; protocol 2 (P2) used all the available contrasts except for double inversion recovery; and protocol 3(P3) used only double inversion recovery. RESULTS: Six hundred forty-three cortical lesions were identified with P1 (mean = 22.96); 633, with P2 (mean = 22.6); and 280, with P3 (mean = 10). The counts obtained by using P1 and P2 were not significantly different (P = .93). The counts obtained by using P3 were significantly smaller than those obtained by using either P1 (P < .001) or P2 (P < .001). The intraclass correlation coefficients were P1 versus P2 = 0.989, P1 versus P3 = 0.615, and P2 versus P3 = 0.588. CONCLUSIONS: MR imaging cortical lesion segmentation can be performed by using 3D T1-weighted and 3D FLAIR images acquired with a 1-mm isotropic voxel size, supported by conventional T2-weighted and proton-density images with 3-mm thick sections. Inclusion of double inversion recovery in this multimodal reading protocol did not significantly improve the cortical lesion identification rate. A multimodal approach is superior to using double inversion recovery alone. PMID- 27197990 TI - Prognostic value of perfusion-weighted magnetic resonance imaging in acute intracerebral hemorrhage. AB - OBJECTIVE: This study intends to investigate the prognostic value of perfusion weighted magnetic resonance imaging in acute intracerebral hemorrhage. METHODS: Demographic, clinical and biochemical data between acute intracerebral hemorrhage (AICH) and healthy volunteer groups were assessed in this study, such as rCBV and MTT values. The optimal cutoff values of rCBV and MTT for diagnosing AICH were determined by the ROC curves. Apart from that, we also investigated the association between rCBV/MTT values and cerebral hematoma volumes of AICH patients. The unconditional logistic regression was conducted to determine significant risk factors for AICH. RESULT: AICH patients have significantly lower rCBV and higher MTT compared to the control group (all P < 0.05). As suggested by the relatively high sensitivity and specificity, both rCBV and MTT values could be utilized for AICH diagnosis. Moreover, rCBV and MTT were significantly associated with the cerebral hematoma volumes of AICH patients (all P < 0.05). Results from unconditional logistic regression analysis revealed that MTT was a significant risk factor for AICH (P < 0.05 and OR > 1), while rCBV is considered as a protective factor (P < 0.05 and OR < 1). CONCLUSION: Perfusion-weighted magnetic resonance imaging produces a high prognostic value for diagnosing AICH. PMID- 27197989 TI - Regional Frontal Perfusion Deficits in Relapsing-Remitting Multiple Sclerosis with Cognitive Decline. AB - BACKGROUND AND PURPOSE: Cortical dysfunction, quantifiable by cerebral perfusion techniques, is prevalent in patients with MS, contributing to cognitive impairment. We sought to localize perfusion distribution differences in patients with relapsing-remitting MS with and without cognitive impairment and healthy controls. MATERIALS AND METHODS: Thirty-nine patients with relapsing-remitting MS (20 cognitively impaired, 19 nonimpaired) and 19 age- and sex-matched healthy controls underwent a neurocognitive battery and MR imaging. Voxel-based analysis compared regional deep and cortical GM perfusion and volume among the cohorts. RESULTS: After we adjusted for localized volumetric differences in the right frontal, temporal, and occipital lobes, progressive CBF and CBV deficits were present in the left middle frontal cortex for all cohorts and in the left superior frontal gyrus for patients with cognitive impairment compared with patients without impairment and controls. Compared with healthy controls, reduced CBF was present in the limbic regions of patients with cognitive impairment, and reduced CBV was present in the right middle frontal gyrus in patients with cognitive impairment and in the temporal gyrus of relapsing-remitting MS patients without cognitive impairment. CONCLUSIONS: Consistent regional frontal cortical perfusion deficits are present in patients with relapsing-remitting MS, with more widespread hypoperfusion in those with cognitive impairment, independent of structural differences, indicating that cortical perfusion may be a useful biomarker of cortical dysfunction and cognitive impairment in MS. PMID- 27197993 TI - Multimodal Superparamagnetic Nanoparticles with Unusually Enhanced Specific Absorption Rate for Synergetic Cancer Therapeutics and Magnetic Resonance Imaging. AB - Superparamagnetic nanoparticles (SPMNPs) used for magnetic resonance imaging (MRI) and magnetic fluid hyperthermia (MFH) cancer therapy frequently face trade off between a high magnetization saturation and their good colloidal stability, high specific absorption rate (SAR), and most importantly biological compatibility. This necessitates the development of new nanomaterials, as MFH and MRI are considered to be one of the most promising combined noninvasive treatments. In the present study, we investigated polyethylene glycol (PEG) functionalized La1-xSrxMnO3 (LSMO) SPMNPs for efficient cancer hyperthermia therapy and MRI application. The superparamagnetic nanomaterial revealed excellent colloidal stability and biocompatibility. A high SAR of 390 W/g was observed due to higher colloidal stability leading to an increased Brownian and Neel's spin relaxation. Cell viability of PEG capped nanoparticles is up to 80% on different cell lines tested rigorously using different methods. PEG coating provided excellent hemocompatibility to human red blood cells as PEG functionalized SPMNPs reduced hemolysis efficiently compared to its uncoated counterpart. Magnetic fluid hyperthermia of SPMNPs resulted in cancer cell death up to 80%. Additionally, improved MRI characteristics were also observed for the PEG capped La1-xSrxMnO3 formulation in aqueous medium compared to the bare LSMO. Taken together, PEG capped SPMNPs can be useful for diagnosis, efficient magnetic fluid hyperthermia, and multimodal cancer treatment as the amphiphilicity of PEG can easily be utilized to encapsulate hydrophobic drugs. PMID- 27197991 TI - Identification, stress tolerance, and antioxidant activity of lactic acid bacteria isolated from tropically grown fruits and leaves. AB - From 6 samples of tropically grown fruits and leaves, 10 lactic acid bacteria belonging Leuconostoc, Weissella, and Lactobacillus species were isolated and identified by 16S rRNA gene sequencing and (GTG)5 fingerprinting. Acidification kinetics determined from BHI broth cultures showed genus-related patterns. In particular, Weissella cibaria appeared to act as a potent acidifier. Tolerance of isolates to acid, oxidative, or salt stress was highly variable and strain dependent. Isolate S14 (Leuconostoc pseudomesenteroides) growth was not affected by the presence of 0.05% H2O2, while Lactobacillus spp. isolates (S17 and S29) were the most tolerant to pH 4.5. The growth of 4 isolates, S5 (Leuconostoc mesenteroides), S14 and S10 (Leuconostoc pseudomesenteroides), and S27 (W. cibaria), was not affected by 5% NaCl. Nutritional beneficial properties were examined through measurement of antioxidant activities of short-term fermented pineapple juice, such as LDL oxidation and polyphenol content, and through exopolysaccharide formation from sucrose. Two isolates, S14 and S27, increased the antioxidant capacity of pineapple juice. The robust capacity of W. cibaria and of Leuconostoc pseudomesenteroides for vegetable lactic fermentation aimed to ameliorate food nutritional and functional quality was highlighted. PMID- 27197992 TI - Multisystemic SYNE1 ataxia: confirming the high frequency and extending the mutational and phenotypic spectrum. PMID- 27197994 TI - Clinical Spectrum and Management of Caustic Ingestion: A Case Series Presenting Three Opposing Outcomes. AB - BACKGROUND: Ingestion of caustic substances is a medical emergency in both the adult and pediatric population and is associated with high morbidity and mortality. The extent of injuries after ingestion of caustic substances depends on the nature, amount, and concentration of the agent and on the exposure time. Acutely, caustic substances may cause massive hemorrhage and gastrointestinal tract perforation; the most markedly affected cases require urgent surgical treatment. Patients surviving the initial event may present with aorto-enteric or gastrocolic fistulae, esophageal strictures, dysphagia, and increased risk of esophageal cancer as long term sequelae. CASE REPORT: The features of three cases of caustic ingestion are reported to demonstrate significantly different complaints presented at the emergency department. Two patients had free gastric perforation, one at presentation, and one delayed. The third patient presented with late severe strictures of the esophagus and pylorus. The outcomes of the three patients are discussed in detail along with the most current management strategies. CONCLUSIONS: Among adults, ingestion of caustic substances is usually associated with more severe lesions due to the increased amount of ingested substance, as compared with pediatric patients. The most serious presentation is that of visceral perforation, most commonly of the stomach and rarely of the esophagus. Management involves urgent resuscitation with correction of fluid and electrolyte and acid-base abnormalities and immediate surgical exploration in those patients with signs of perforation. Once the perioperative period is managed successfully, the long-term results can be satisfactory. Managing of strictures or else reconstructive procedures must be well timed to allow for psychological and nutritional rehabilitation. PMID- 27197997 TI - Differences in Gene Regulation by Dual Ligands of Nuclear Receptors Constitutive Androstane Receptor (CAR) and Pregnane X Receptor (PXR) in HepG2 Cells Stably Expressing CAR/PXR. AB - The constitutive androstane receptor (CAR) and pregnane X receptor (PXR) regulate various genes involved in xenobiotics and drug metabolism. In many cases, CAR/PXR share ligands termed dual ligands of CAR/PXR. It is difficult to investigate the effect of CAR/PXR dual ligands in cell lines because CAR and PXR expression is scarcely detected in cultured cell lines. Here, we established a tetracycline inducible human CAR and stably human PXR-overexpressing HepG2 cell line (HepTR/hCAR/hPXR) to examine CAR/PXR dual ligands. In the present study, we investigated the regulation of CYP2B6, CYP2C9, CYP3A4, and UDP-glucuronosyl transferase, which are target genes of CAR/PXR, by dual ligands of CAR/PXR in two transfectants. Activation of CAR and PXR in cells treated with a high dose of CITCO [6-(4-chlorophenyl)-imidazo(2,1-b)thiazole-5-carbaldehyde] or cotreated with rifampicin and tetracycline resulted in synergistic enhancement of CYP3A4, but not CYP2B6, CYP2C9, or UGT1A1, mRNA expression in HepTR/hCAR/hPXR cells. In contrast, this synergistic effect was not observed in HepTR/hCAR cells. These observations were also demonstrated in human primary hepatocytes. Taken together, our results suggest that dual ligands of CAR/PXR show distinct gene regulation patterns by cross-talk between CAR and PXR. Furthermore, the two newly established cell lines are useful tools to investigate dual ligands of CAR/PXR. PMID- 27197998 TI - DCD liver transplant infection: experience from a single centre in China. AB - AIM: The purpose of our study was to evaluate the incidence, timing, location and risk factors for bacterial and fungal infections after donation after cardiac death (DCD) liver transplant and clearly delineate any relationship between infection and survival in DCD liver transplant recipients. METHODS: We retrospectively reviewed 257 consecutive patients undergoing DCD liver transplant between October 2010 and May 2015 at our centre. RESULTS: A total of 133 patients (51.8%) developed at least one bacterial or fungal infection episode. The predominant infection site was the respiratory tract, followed by the blood stream. Most of the infections occurred within the first week after liver transplant (61.9%). A recipient respiratory support time greater than 7 days (p = 0.041), post-transplant hospital time greater than 24 days (p = 0.002) and renal failure after DCD liver transplant (p = 0.039) were independent predictors of bacterial and fungal infection. The area under the receiver operating characteristic (ROC) curve (AUC) of the transplant infection risk assessment model was 0.788. The 1- and 3-year survival rates for recipients without infection were significantly increased compared with recipients with infection (96.1% and 89.0% vs. 81.5% and 75.9%, p = 0.007). CONCLUSION: This is the first study that offers detailed data revealing the timing and incidence of bacterial and fungal infection among adult DCD liver transplant recipients. Bacterial and fungal infection occurs at a high rate during the first week after DCD liver transplant, especially in patients with prolonged respiratory support time and renal failure, and infection is related to increased hospital stay. PMID- 27198000 TI - Microbial epidemiology and risk factors of infections in recipients after DCD liver transplantation. AB - AIM: Infection is a major cause of increased mortality after a liver transplant (LT). This study sought to identify the incidence, prevalence and risk factors of microbial infection for recipients who underwent LT using grafts from donors after cardiac death (DCD). METHODS: We retrospectively analysed the frequency and characteristics of post-transplantation infections in 236 recipients who underwent DCD LT between 1 January 2010 and 31 December 2014 in our centre and evaluated the risk factors of post-transplantation infection. RESULTS: Overall, 162 recipients acquired at least one type of infection during hospitalisation after LT, and the morbidity rate was 68.6%. Moreover, 19 of the 236 recipients died, with an overall mortality rate of 8.1%. In total, 752 pathogens were isolated. Gram-positive bacteria, Gram-negative bacteria and fungi accounted for 26.1% (196), 58.2% (438) and 15.7% (118) of the pathogens, respectively. Kaplan Meier curves of 1-year survival showed that recipients with infection had a significantly lower cumulative survival rate compared with those without infection (83.2% vs. 90.6%, p < 0.05). Multivariate analysis revealed that age > 60 years (p = 0.010) and severe hepatitis (p = 0.036) were independent risk factors for infection during hospitalisation after LT. CONCLUSION: Infection is a common complication after a DCD-LT that could impair 1-year survival. We suggest physicians pay more attention to the infection of recipients post-LT, especially those recipients greater than 60 years of age and those who suffered from severe hepatitis. PMID- 27197999 TI - Peripheral blood CD4(+) cell ATP activity measurement to predict HCC recurrence post-DCD liver transplant. AB - BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) recurrence after orthotopic liver transplantation (OLT) continues to confound transplant surgeons and physicians. There are no effective methods to predict the patients at risk for recurrence so far although many studies have sought meaningful biomarkers. The ImmuKnow (IMK) assay is an immune cell function assay that detects cell-mediated immunity in an immunosuppressed population, mainly measuring peripheral blood CD4(+) adenosine triphosphate (ATP) release. The aim of this study was to assess the relationship between cellular immune function measured by the ImmuKnow assay and HCC recurrence post-OLT. METHODS: A total of 76 HCC cases underwent Donation after Cardiac Death (DCD) liver transplant, which confirmed hepatocellular carcinoma by histology postoperatively. The ImmuKnow assay was prospectively performed in these cases at a range of 6-36 months post-OLT. Every test was repeated 1 week later, obtaining the average value for every patient. In addition, every case had liver imaging findings at approximately the exam time. RESULTS: Fifteen cases with liver imaging findings showed HCC recurrence (19.7%) post-OLT, and the average ImmuKnow assay in these patients was 190 +/- 48 ng/ml, which was less (p < 0.05) than in patients without HCC recurrence, whose average ATP level was 313 +/- 90 ng/ml. ATP levels post-OLT were found to be significantly associated with the risk of tumour recurrence. The ratio of T reg cells and the levels of TGFbeta and IL-10 were higher in recurrence patients than in recurrence-free patients. CONCLUSION: Greater suppression of cellular immunity, as measured by the ImmuKnow assay, was associated with progression of HCC recurrence post-OLT. ImmuKnow assay was helpful in determining the risk of early recurrence of HCC postliver transplant. A pathway consisting of T reg cells, TGFbeta and IL-10 might be the HCC recurrence-predominant pathway. PMID- 27198001 TI - The efficacy and safety of intensified enteric-coated mycophenolate sodium with low exposure of calcineurin inhibitors in Chinese de novo kidney transplant recipients: a prospective study. AB - AIMS: The aim of this study was to investigate the efficacy and safety of a transient intensified enteric-coated mycophenolate sodium (EC-MPS) dosing regimen with low exposure of calcineurin inhibitors (CNIs) in Chinese de novo kidney transplantation. METHODS: In a 6-month prospective study, a total of 97 recipients were enrolled and assigned to either an intensified EC-MPS dosing (IS) regimen or a standard EC-MPS dosing (SD) regimen. The area under the curve (AUC) of MPA was assessed at week 1 post transplant. The incidences of acute rejection, patient and graft survival, renal allograft function and adverse events were analysed. RESULTS: The IS regimen displayed a trend of acute rejection risk reduction (IS 2.7% vs. SD 13.3%, p = 0.061) and allograft function improvement (IS 62.8 +/- 14.0 ml/min per 1.73 m(2) vs. SD 56.6 +/- 18.3 ml/min per 1.73 m(2) , p = 0.084) after 6-month follow-up. MPA-AUC0-12 h was substantially higher in the intensified EC-MPS group than the standard EC-MPS group, though without a significant difference (71.4 +/- 41.7 vs. 53.0 +/- 27.0 mg.h/l, p = 0.107). The IS regimen did not increase the incidence of adverse effects (IS 54.1% vs. 45.0%, p = 0.39), including diarrhoea or leucopenia. CONCLUSIONS: The intensified EC-MPS dosing regimen maintaining low-dose CNIs in this study may be beneficial for Chinese adult de novo kidney transplant recipients in terms of acute rejection and allograft function and is safe within 6 months post transplant. PMID- 27198002 TI - Paediatric liver re-transplantation after primary partial liver graft transplantation: a report of four cases. AB - OBJECTIVE: To discuss rules of anatomic shifting of the porta hepatis structures of the original graft and dissection techniques for the portal vein (pull-out technique) in pediatric liver re-transplantation. METHOD: We summarized four cases of paediatric liver re-transplantation. The main donor type is partial liver graft especially using the left lateral lobe. RESULT: In paediatric liver re-transplantation, gross morphological changes were observed in the liver, and the spatial position of the porta hepatis structures was shifted clockwise (with the anastomosis of the hepatic vein as the origin). Preoperative three dimensional imaging showed that segment 3 of the liver graft increased in a compensatory manner. The pull-out technique could expose the surgical field without dissection and separation, and reduce the technical difficulty of identifying and dissociating the anatomical structures. CONCLUSION: Changes in the spatial location and structure of the liver portal anatomy increase the difficulties and risks of surgery. We can reduce the difficulty of surgical anatomy, and the risk of bleeding and injury and increase the safety of paediatric liver re-transplantation by evaluation and the application of special techniques. PMID- 27198003 TI - Fast MS/MS acquisition without dynamic exclusion enables precise and accurate quantification of proteome by MS/MS fragment intensity. AB - Most currently proteomic studies use data-dependent acquisition with dynamic exclusion to identify and quantify the peptides generated by the digestion of biological sample. Although dynamic exclusion permits more identifications and higher possibility to find low abundant proteins, stochastic and irreproducible precursor ion selection caused by dynamic exclusion limit the quantification capabilities, especially for MS/MS based quantification. This is because a peptide is usually triggered for fragmentation only once due to dynamic exclusion. Therefore the fragment ions used for quantification only reflect the peptide abundances at that given time point. Here, we propose a strategy of fast MS/MS acquisition without dynamic exclusion to enable precise and accurate quantification of proteome by MS/MS fragment intensity. The results showed comparable proteome identification efficiency compared to the traditional data dependent acquisition with dynamic exclusion, better quantitative accuracy and reproducibility regardless of label-free based quantification or isobaric labeling based quantification. It provides us with new insights to fully explore the potential of modern mass spectrometers. This strategy was applied to the relative quantification of two human disease cell lines, showing great promises for quantitative proteomic applications. PMID- 27198005 TI - Exploring the implementation of poslansia, Indonesia's community-based health programme for older people. AB - AIM: To explore the implementation of poslansia, a community-based integrated health service implemented across Indonesia to improve the health status of older people through health promotion and disease prevention. METHODS: Data analysis of 307 poslansia surveyed in the 4th wave of Indonesia Family Life Survey (IFLS-4). We examined the services provided in the programme, resources and perceived problems. RESULTS: The services provided by poslansia focused mostly on risk factor screening and treatment for minor illness, and less on health promotion activities. Lack of support from community health centres, no permanent place for holding poslansia and lack of participant interest in joining the programme were associated with fewer services provided in the programme (P < 0.05). CONCLUSION: The findings indicate existing support from the community, community health centres and related institutions for poslansia is not adequate for optimal service function. Health awareness among the older population should also be increased for programme sustainability. PMID- 27198004 TI - Diverse Genetic Background of Multidrug-Resistant Pseudomonas aeruginosa from Mainland China, and Emergence of an Extensively Drug-Resistant ST292 Clone in Kunming. AB - For a better understanding of the multidrug resistant Pseudomonas aeruginosa (MDR PA) epidemiology in mainland China, a nationwide surveillance network of 27 tertiary hospitals was established. Non-duplicate MDR-PA isolates from 254 cases of nosocomial infections, were collected during the period August 2011 to July 2012. Minimum inhibitory concentrations (MICs) of nine antimicrobial agents were determined by broth micro-dilution method according to the CLSI guidelines [M7 A10]. Genotyping analysis was performed by multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). The presence of acquired carbapenemases was also determined by molecular approaches for 233 carbapenem-resistant isolates. Carbapenemase genes were detected in 19 (8.2%) isolates, with 13 of these isolates encoding IMP-type enzymes, five with VIM-2, and one with KPC-2. MLST analysis revealed significant genetic diversity among the MDR-PA isolates studied, and 91 STs (including 17 novel STs) were identified. However, a long term outbreak of an emerging extensively drug-resistant (XDR) ST292/PFGE genotype A clone was detected in a hospital from Southwest China. This study has demonstrated that MDR-PA in mainland China have evolved from diverse genetic backgrounds. Evidence of clonal dissemination of the organism and nosocomial outbreaks in some regions, suggest a need to strengthen existing infection control measures. PMID- 27198006 TI - Statin-induced expression change of INSIG1 in lymphoblastoid cell lines correlates with plasma triglyceride statin response in a sex-specific manner. PMID- 27198007 TI - Draft Genome Sequence of Streptomyces hygroscopicus subsp. hygroscopicus NBRC 16556. AB - Here, we report the draft genome sequence of strain NBRC 16556, deposited as Streptomyces hygroscopicus subsp. hygroscopicus into the NBRC culture collection. An average nucleotide identity analysis confirmed that the taxonomic identification is correct. The genome sequence will serve as a valuable reference for genome mining to search new secondary metabolites. PMID- 27198008 TI - Complete Genome Sequence of a Novel Avian Paramyxovirus (APMV-13) Isolated from a Wild Bird in Kazakhstan. AB - A novel avian paramyxovirus was identified during annual viral surveillance of wild bird populations in Kazakhstan in 2013. The virus was isolated from a white fronted goose (Anser albifrons) in northern Kazakhstan. Here, we report the complete genome sequence of the isolate, which we suggest should constitute a novel serotype. PMID- 27198009 TI - Complete Genome Sequences of Eight Human Papillomavirus Type 16 Asian American and European Variant Isolates from Cervical Biopsies and Lesions in Indian Women. AB - Human papillomavirus type 16 (HPV16), a member of the Papillomaviridae family, is the primary etiological agent of cervical cancer. Here, we report the complete genome sequences of four HPV16 Asian American variants and four European variants, isolated from cervical biopsies and scrapings in India. PMID- 27198010 TI - Genome Sequence of Propionibacterium acidipropionici ATCC 55737. AB - Propionibacterium acidipropionici produces propionic acid as its main fermentation product. Traditionally derived from fossil fuels, environmental and sustainable issues have revived the interest in producing propionic acid using biological resources. Here, we present the closed sequence of Propionibacterium acidipropionici ATCC 55737, an efficient propionic acid producer. PMID- 27198011 TI - Complete Genome Sequence of Mycobacterium tuberculosis Clinical Isolate Spoligotype SIT745/EAI1-MYS. AB - Mycobacterium tuberculosis is known to cause pulmonary and extrapulmonary tuberculosis. This organism showed special phylogeographical specificity. Here, we report the complete genome sequence of M. tuberculosis clinical isolate spoligotype SIT745/EAI1-MYS, which was isolated from a Malaysian tuberculosis patient. PMID- 27198012 TI - Chloroplast Genome Sequence of Lagerstroemia guilinensis (Lythraceae, Myrtales), a Species Endemic to the Guilin Limestone Area in Guangxi Province, China. AB - We announce here the first complete chloroplast genome sequence of Lagerstroemia guilinensis (Lythraceae, Myrtales), a species endemic to the Guilin limestone area, along with its genome structure and functional gene annotations. The plant was collected from Guilin, Guangxi, China, and deposited as a germplasm accession of the Zhejiang Agriculture and Forestry University Collection (ZAFU 1507144). This genome will provide valuable information for future research of the Lagerstroemia genus and its relatives. PMID- 27198013 TI - First Genome Sequence of Leptospira interrogans Serovar Pomona, Isolated from a Bovine Abortion. AB - Leptospirosis is a widespread zoonosis and a re-emergent disease of global distribution with major relevance in veterinary production. Here, we report the whole-genome sequence of Leptospira interrogans serovar Pomona strain AKRFB, isolated from a bovine abortion during a leptospirosis outbreak in Argentina. PMID- 27198014 TI - Draft Genome Sequence of Pseudomonas fluorescens Strain ET76, Isolated from Rice Rhizosphere in Northwestern Morocco. AB - Pseudomonas fluorescens ET76 was isolated from rice rhizosphere in northwestern Morocco. Its draft genome was estimated to be 6,681,652 bp with 5,789 coding sequences (CDSs). Genes encoding for type I to VI secretion systems, PvdQ, proteases, siderophores, hydrogen cyanide synthase, ACC-deaminase, among others, highlight its potential use in biological control of plant pathogens. PMID- 27198015 TI - The Draft Genome Sequence of Paenibacillus polymyxa Strain CCI-25 Encompasses High Potential for Secondary Metabolite Production. AB - We report here the draft genome sequence of Paenibacillus polymyxa strain CCI-25, which displays strong antifungal and antibacterial activities in vitro The genome encompasses nonribosomal peptide synthetases predicted to encode a tridecaptin, polymyxin, fusaricidin, an iturin-like synthetase, a lantibiotic similar to paenicidin A, as well as a type 1 polyketide synthase. PMID- 27198016 TI - Genome Sequence of Serratia plymuthica A153, a Model Rhizobacterium for the Investigation of the Synthesis and Regulation of Haterumalides, Zeamine, and Andrimid. AB - The rhizobacterium Serratia plymuthica A153 is a Gram-negative bacterium belonging to the family Enterobacteriaceae Here, we present the genome sequence of this strain, which produces multiple bioactive secondary metabolites, including the halogenated macrolide oocydin A, the polyamino antibiotic zeamine, and the bacterial acetyl-CoA carboxylase inhibitor andrimid. PMID- 27198017 TI - Draft Genome Sequence of a Multidrug-Resistant Klebsiella pneumoniae Strain Isolated from King Abdullah Medical City, Makkah, Saudi Arabia. AB - Multidrug-resistant (MDR) Gram-negative infections represent a growing problem and a serious global threat. Carbapenem-resistant Klebsiella pneumoniae is perhaps cause the most difficult infection to treat and is associated with increased morbidity and mortality. Here, we report the draft genome sequence of an MDR K. pneumoniae strain isolated from Makkah, Saudi Arabia. PMID- 27198019 TI - First Insights into the Genome Sequence of the Halophilic Archaeon Halalkalicoccus paucihalophilus (DSM 24557). AB - Halalkalicoccus paucihalophilus is an extremely halophilic, Gram-negative, and nonmotile coccus-like archaeon, which was originally isolated from the Lop Nur region in the northwest of China. The genome consists of a single replicon (3.98 Mbp). H. paucihalophilus is able to utilize mannose, which is unique for members of this genus. PMID- 27198020 TI - Draft Genome Sequence of a Novel Acidophilic Iron-Oxidizing Firmicutes Species, "Acidibacillus ferrooxidans" (SLC66T). AB - Here, we present the draft genome sequence of the type strain of "Acidibacillus ferrooxidans," a mesophilic, heterotrophic, and acidophilic bacterium that was isolated from mine spoilage subjected to accelerated weathering in humidity cell tests carried out by the former U.S. Bureau of Mines in Salt Lake City, UT. PMID- 27198018 TI - Complete Genome Sequence of a Marine Bacterium, Pseudomonas pseudoalcaligenes Strain S1, with High Mercury Resistance and Bioaccumulation Capacity. AB - Pseudomonas pseudoalcaligenes S1, a marine bacterium, exhibited strong resistance to a high concentration of Hg(2+) and remarkable Hg(2+) bioaccumulation capacity. Here, we report the 6.9-Mb genome sequence of P. pseudoalcaligenes S1, which may help clarify its phylogenetic status and provide further understanding of the mechanisms of mercury bioremediation in a marine environment. PMID- 27198021 TI - First Insights into the Draft Genome of Clostridium colicanis DSM 13634, Isolated from Canine Feces. AB - Clostridium colicanis DSM 13634 is a strictly anaerobic, rod-shaped, and spore forming bacterium. It produces acids from common sugars such as glucose and fructose. The draft genome consists of one chromosome (2.6 Mbp) and contains 2,159 predicted protein-encoding genes. PMID- 27198022 TI - Complete Genome Sequence of Enterococcus faecium ATCC 700221. AB - We report the complete genome sequence of a vancomycin-resistant isolate of Enterococcus faecium derived from human feces. The genome comprises one chromosome of 2.9 Mb and three plasmids. The strain harbors a plasmid-borne vanA type vancomycin resistance locus and is a member of multilocus sequencing type (MLST) cluster ST-17. PMID- 27198023 TI - Permanent Draft Genome Sequence of Frankia sp. Strain Allo2, a Salt-Tolerant Nitrogen-Fixing Actinobacterium Isolated from the Root Nodules of Allocasuarina. AB - Frankia sp. strain Allo2 is a member of Frankia lineage Ib, which is able to reinfect plants of the Casuarinaceae family, and exhibits a high level of salt tolerance compared to other isolates. Here, we report the 5.3-Mbp draft genome sequence of Frankia sp. strain Allo2 with a G+C content of 70.0% and 4,224 candidate protein-encoding genes. PMID- 27198024 TI - Draft Genome Sequence of the Oleaginous Yeast Cryptococcus albidus var. albidus. AB - We report the complete draft genome sequence of Cryptococcus albidus var. albidus, an oleaginous yeast, which can utilize various organic carbon sources for lipid synthesis. Availability of this genome will help elucidate factors driving lipid accumulation in C. albidus and contribute toward bioprocess development and optimization for engineered lipid production. PMID- 27198025 TI - Complete Sequence of the Smallest Polyomavirus Genome, Giant Guitarfish (Rhynchobatus djiddensis) Polyomavirus 1. AB - Polyomaviruses are known to infect mammals and birds. Deep sequencing and metagenomic analysis identified the first polyomavirus from a cartilaginous fish, the giant guitarfish (Rhynchobatus djiddensis). Giant guitarfish polyomavirus 1 (GfPyV1) has typical polyomavirus genome organization, but is the smallest polyomavirus genome (3.96 kb) described to date. PMID- 27198026 TI - Draft Genome Sequence of an Oxalate-Degrading Strain of Clostridium sporogenes from the Gastrointestinal Tract of the White-Throated Woodrat (Neotoma albigula). AB - The gastrointestinal tract of the white-throated woodrat Neotoma albigula harbors a diverse microbial population that functions in the degradation of ingested plant secondary compounds. Here, we present the draft genome sequence and annotation of Clostridium sporogenes strain 8-O, a novel oxalate-degrading bacterium isolated from the feces of N. albigula. PMID- 27198027 TI - Draft Genome Sequence of Limnobacter sp. Strain CACIAM 66H1, a Heterotrophic Bacterium Associated with Cyanobacteria. AB - Ecological interactions between cyanobacteria and heterotrophic prokaryotes are poorly known. To improve the genomic studies of heterotrophic bacterium cyanobacterium associations, the draft genome sequence (3.2 Mbp) of Limnobacter sp. strain CACIAM 66H1, found in a nonaxenic culture of Synechococcus sp. (cyanobacteria), is presented here. PMID- 27198028 TI - Draft Genome Sequence of Flavihumibacter sp. Strain CACIAM 22H1, a Heterotrophic Bacterium Associated with Cyanobacteria. AB - Here, we present a draft genome and annotation of Flavihumibacter sp. CACIAM 22H1, isolated from Bolonha Lake, Brazil, which will provide further insight into the production of substances of biotechnological interest. PMID- 27198029 TI - Genetic Characterization of Providence Virus Isolated from Bat Guano in Hungary. AB - We report the complete genome sequence and genetic characterization of a novel strain of Providence virus, detected in Barbastella barbastellus bat guano, collected in Hungary in 2014. Our data may facilitate the understanding of the evolutionary processes of this unique viral family of Carmotetraviridae. PMID- 27198030 TI - Complete Genome Sequence of Murine Pneumotropic Virus (Polyomaviridae) Clone pKV(37-1). AB - The murine pneumotropic virus genome encoded by the pKV(37-1) clone was sequenced to completion. The regulatory region harbored a mutation not previously reported. The protein coding regions (large and small T antigens, viral proteins 1 to 3) showed multiple regions of high amino acid identity to the human, simian, and bovine polyomaviruses. PMID- 27198031 TI - Draft Genome Sequence of an Aldoxime Degrader, Rhodococcus sp. Strain YH3-3. AB - Rhodococcus sp. strain YH3-3 has been isolated as an (E)-pyridine-3-aldoxime degrader. Here, we report the draft genome sequence of this strain, with a size of 7,316,908 bp, average G+C content of 62.15%, and 7,281 predicted protein coding sequences. PMID- 27198032 TI - Draft Genome Sequence of Flavobacterium sp. Strain TAB 87, Able To Inhibit the Growth of Cystic Fibrosis Bacterial Pathogens Belonging to the Burkholderia cepacia Complex. AB - We report here the draft genome sequence of the Flavobacterium sp. TAB 87 strain, isolated from Antarctic seawater during a summer campaign near the French Antarctic station Dumont d'Urville (60 degrees 40'S, 40 degrees 01'E). It will allow for comparative genomics and the fulfillment of both fundamental and application-oriented investigations. It allowed the recognition of genes associated with the production of bioactive compounds and antibiotic resistance. PMID- 27198033 TI - Complete Nucleotide Sequences and Genome Organization of Two Pepper Mild Mottle Virus Isolates from Capsicum annuum in South Korea. AB - The complete genome sequences of pepper mild mottle virus (PMMoV)-P2 and -P3 were determined by the Sanger sequencing method. Although PMMoV-P2 and PMMoV-P3 have different pathogenicity in some pepper cultivars, the complete genome sequences of PMMoV-P2 and -P3 are composed of 6,356 nucleotides (nt). In this study, we report the complete genome sequences and genome organization of PMMoV-P2 and -P3 isolates from pepper species in South Korea. PMID- 27198034 TI - Complete Genomic Characterization of Plum bark necrosis stem pitting-associated virus Infecting Sweet Cherry in China. AB - Plum bark necrosis stem pitting-associated virus (PBNSPaV) causes the plum bark necrosis stem pitting-associated disease. We obtained the complete genome of a PBNSPaV isolate (PBNSPaV-TA) using small RNA deep sequencing followed by overlapping RT-PCR. To our knowledge, this is the first report of a completed genome of PBNSPaV identified from cherry trees. PMID- 27198035 TI - Genome Sequence of Enterococcus pernyi, a Pathogenic Bacterium for the Chinese Oak Silkworm, Antheraea pernyi. AB - We report the draft genome assembly of Enterococcus pernyi The genome sequence is 3.09 Mb in length with a G+C content of 38.35%. It covers 3,153 genes with an average length of 854 bp, and contains 65 tRNAs, 13 small RNAs, and 18 rRNAs. Moreover, it contains 9 genomic islands with an average length of 14,058 bp and 3 prophages with an average length of 37,430 bp. PMID- 27198036 TI - The effects of vitamin D, K and calcium co-supplementation on carotid intima media thickness and metabolic status in overweight type 2 diabetic patients with CHD. AB - This study was conducted to examine the effects of vitamin D, K and Ca co supplementation on carotid intima-media thickness (CIMT) and metabolic status in overweight diabetic patients with CHD. This randomised, double-blind, placebo controlled trial was conducted among sixty-six diabetic patients with CHD. Participants were randomly allocated into two groups to take either 5ug vitamin D, 90 ug vitamin K plus 500 mg Ca supplements (n 33) or placebo (n 33) twice a day for 12 weeks. Fasting blood samples were obtained at the beginning of the study and after the 12-week intervention period to determine related markers. Vitamin D, K and Ca co-supplementation resulted in a significant reduction in maximum levels of left CIMT (-0.04 (sd 0.22) v. +0.04 (sd 0.09) mm, P=0.02). Changes in serum vitamin D (+6.5 (sd 7.8) v. +0.4 (sd 2.2) ng/ml, P<0.001), Ca (+0.6 (sd 0.3) v. +0.1 (sd 0.1) mg/dl, P<0.001) and insulin concentrations (-0.9 (sd 3.1) v. +2.6 (sd 7.2) uIU/ml, P=0.01), homoeostasis model for assessment of estimated insulin resistance (-0.4 (sd 1.2) v. +0.7 (sd 2.3), P=0.01), beta-cell function (-2.1 (sd 9.0) v. +8.9 (sd 23.7), P=0.01) and quantitative insulin sensitivity check index (+0.007 (sd 0.01) v. -0.006 (sd 0.02), P=0.01) in supplemented patients were significantly different from those in patients in the placebo group. Supplementation resulted in significant changes in HDL-cholesterol (+2.7 (sd 7.0) v. -2.5 (sd 5.7) mg/dl, P=0.002), high-sensitivity C-reactive protein (-1320.1 (sd 3758.3) v. +464.0 (sd 3053.3) ng/ml, P=0.03) and plasma malondialdehyde concentrations (-0.4 (sd 0.5) v. -1.0 (sd 1.1) umol/l, P=0.007) compared with placebo. Overall, vitamin D, K and Ca co-supplementation for 12 weeks among diabetic patients with CHD had beneficial effects on maximum levels of left CIMT and metabolic status. The effect of vitamin D, K and Ca co supplementation on maximum levels of left CIMT could be a chance finding. PMID- 27198037 TI - Remission of Unresectable Lung Metastases from Rectal Cancer After Herbal Medicine Treatment: A Case Report. AB - Lung metastasis is frequent in rectal cancer patients and has a poor prognosis, with an expected three-year survival rate of about 10%. Though western medicine has made great strides in the curative resection of liver metastases, resection of lung metastases has lagged far behind. Many preclinical studies have suggested that herbal treatments block metastasis, but few clinical studies have addressed this topic. We present the case of a 57-year-old Asian male with lung metastases from rectal cancer. He first underwent resection of the primary lesion (stage IIA, T3N0M0) and six cycles of adjuvant chemotherapy. Unfortunately, lung metastases were confirmed about one year later. Palliative chemotherapy was begun, but his disease continued to progress after three cycles and chemotherapy was halted. The patient was exclusively treated with herbal medicine-standardized allergen-removed Rhus verniciflua stokes extract combined with Dokhwaljihwang tang (Sasang constitutional medicine in Korea). After seven weeks of herbal medicine treatment, the lung metastases were markedly improved. Regression of lung metastases has continued; also, the patient's rectal cancer has not returned. He has been receiving herbal medicine for over two years and very few side effects have been observed. We suggest that the herbal regimen used in our patient is a promising candidate for the treatment of lung metastases secondary to rectal cancer, and we hope that this case stimulates further investigation into the efficacy of herbal treatments for metastatic colorectal cancer patients. PMID- 27198038 TI - The Effects of a Home-Based Connective Tissue Targeting Therapy on Hip Development in Children With Cerebral Palsy: Six Case Reports. AB - Hip subluxation in children with Cerebral Palsy (CP) has an incidence of 10-30 %, and children with severe CP having the highest incidence. The condition deteriorates if left untreated. Surgery is the most common method used in managing hip subluxation because standard conservative therapies do not improve it. Surgery may have to be repeated and comes at a biological cost to the child. A new home-based CAM, Advanced Biomechanical Rehabilitation (ABR), has shown encouraging results leading to improved spinal stability and stability in sitting in children with severe CP. This case report examines hip development over time in six children with severe CP in the ABR Program. Changes in their clinical picture and pelvic X-Rays are reported. ABR appeared to help stabilize and improve hip subluxation, resulting in these children not requiring further surgical intervention. These findings warrant further investigation of ABR as a noninvasive therapy for hip subluxation. PMID- 27198039 TI - The Effect of Curanderismo on Chronic Non-malignant Pain: A Case Report. AB - This case study describes the effects of the use of curanderismo, an indigenous healing modality combining techniques in massage, sound, and aromatherapy, on a patient with chronic pain. Despite being a commonly used health practice in certain populations, little is reported in the medical literature about the use of curanderismo. Case report as part of a larger randomized trial of curanderismo for chronic pain. Setting was a community-based hospital affiliated primary care clinic. An adult patient with chronic, opioid dependent back pain following an injury, and subsequent spinal fusion was treated. Intervention was the patient received 33 curanderismo treatment sessions over 10 months in addition to ongoing conventional treatment at a community-based chronic pain management clinic. Main outcomes measures were self-reported assessments of pain, functional ability, mood, insomnia, and narcotic usage. Secondary outcome measure was qualitative interview. Although there was no change in quantitative self-reported pain measures, the patient reported improved function, mood, and sleep as well as decreased narcotic usage. Curanderismo, in addition to conventional pain management, improved patient reported symptoms and functional ability, led to healthy lifestyle changes, and decreased narcotic usage. Controlled studies are needed to confirm the benefit of curanderismo as safe, non-interventional, and cost-effective adjunct for chronic pain management. PMID- 27198040 TI - Unravelling the mechanisms of a protein refolding process based on the association of detergents and co-solvents. AB - A new technique associating the detergent Sodium Dodecyl Sulphate (SDS) and an alcohol-type co-solvent has been set up, showing an unexpected efficiency to refold several types of soluble or membrane proteins. The present contribution deepens the fundamental knowledge on the phenomena underlying this process, considering the refolding of two model peptides featuring the main protein secondary structures: alpha-helix and beta-sheet. Their refolding was monitored by fluorescence and circular dichroism, and it turns out that: (i) 100% recovery of the folded structure is observed for both peptides, (ii) the highest the SDS concentration, the more co-solvent to be added to recover the peptides' native structures, (iii) a high alcohol concentration is required to alter the SDS denaturing properties, (iv) the co-solvent performance relies on its specific lipophilic-hydrophilic balanced character, (v) the size of the micelle formed by the detergent does not enter the process critical parameters, and (vi) increasing the salt concentration up to 1 M NaCl has a beneficial impact on the process efficiency. These mechanistic aspects will help us to improve the method and extend its application. Copyright (c) 2016 European Peptide Society and John Wiley & Sons, Ltd. PMID- 27198041 TI - Corrigendum: Unlocking the genetic diversity of Creole wheats. PMID- 27198042 TI - Plasma oxidative stress level of IgA nephropathy in children and the effect of early intervention with angiotensin-converting enzyme inhibitors. AB - AIM: The purpose of this study was to investigate the change of the plasma oxidative stress level in children with IgA nephropathy (IgAN) and analyze its relativity to the clinical and pathological classification. To discuss the early effects of angiotensin-converting enzyme inhibitors (ACEIs) on the plasma oxidative stress level in children with IgA nephropathy. METHODS: Thirty-eight children with IgAN were divided into groups according to their clinical features, pathologic grades, and treatments. Twenty healthy children were included in the control group. RESULTS: The plasma level of advanced oxidation protein products (AOPPs), malonaldehyde (MDA), and superoxide dismutase (SOD) were detected. The plasma level of oxidative stress was significantly increased in the IgAN group, including a higher plasma level of AOPP and MDA and a lower plasma level of SOD. After treatment, the plasma level of oxidative stress was significantly decreased in the ACEI group. CONCLUSIONS: The children with IgAN had an increase in the plasma level of oxidative stress, expressed as an increased plasma level of AOPP and MDA and a decreased plasma level of SOD. Oxidative stress was associated with the progression of IgAN in children. Early treatment with ACEI therapy can significantly reduce the plasma level of oxidative stress in children with IgAN. PMID- 27198043 TI - Live single-cell laser tag. AB - The ability to conduct image-based, non-invasive cell tagging, independent of genetic engineering, is key to cell biology applications. Here we introduce cell labelling via photobleaching (CLaP), a method that enables instant, specific tagging of individual cells based on a wide array of criteria such as shape, behaviour or positional information. CLaP uses laser illumination to crosslink biotin onto the plasma membrane, coupled with streptavidin conjugates to label individual cells for genomic, cell-tracking, flow cytometry or ultra-microscopy applications. We show that the incorporated mark is stable, non-toxic, retained for several days, and transferred by cell division but not to adjacent cells in culture. To demonstrate the potential of CLaP for genomic applications, we combine CLaP with microfluidics-based single-cell capture followed by transcriptome-wide next-generation sequencing. Finally, we show that CLaP can also be exploited for inducing transient cell adhesion to substrates for microengineering cultures with spatially patterned cell types. PMID- 27198044 TI - Imaging Tumor Vascularity and Response to Anti-Angiogenic Therapy Using Gaussia Luciferase. AB - We developed a novel approach to assess tumor vascularity using recombinant Gaussia luciferase (rGluc) protein and bioluminescence imaging. Upon intravenous injection of rGluc followed by its substrate coelenterazine, non-invasive visualization of tumor vascularity by bioluminescence imaging was possible. We applied this method for longitudinal monitoring of tumor vascularity in response to the anti-angiogenic drug tivozanib. This simple and sensitive method could be extended to image blood vessels/vasculature in many different fields. PMID- 27198047 TI - From the Editor's desk...: June 2016. AB - TREATED HEPATITIS C VIRUS (HCV) CIRRHOTIC PATIENTS CAN HAVE NORMAL LIFE EXPECTANCY: The fact that a sustained virologic response (SVR) is associated with an improved outcome of chronic HCV infection, has been demonstrated in several studies by comparing patients with and without SVR. The study by Bruno et al., however, is the first to demonstrate that patients with compensated cirrhosis who achieve SVR will have a life expectancy similar to that of the sex- and age matched general population. Patients were enrolled in historical prospective cohort studies from tertiary referral centers from Northern and Southern Italy. They were representative of the Italian general population, allowing for adequate comparison of patients long-term 10- and 20-year survival with national data. Intriguing observations of a trend to worse survival was observed in patients with compensated cirrhosis Child-Pugh class A6 as compared to A5. The incidence of hepatocellular carcinoma (HCC) during follow-up after SVR was also not negligible, underscoring the need for early treatment initiation, hereby preventing cirrhosis development as the main HCC determinant. PMID- 27198045 TI - Glycosyltransferase Gene Expression Profiles Classify Cancer Types and Propose Prognostic Subtypes. AB - Aberrant glycosylation in tumours stem from altered glycosyltransferase (GT) gene expression but can the expression profiles of these signature genes be used to classify cancer types and lead to cancer subtype discovery? The differential structural changes to cellular glycan structures are predominantly regulated by the expression patterns of GT genes and are a hallmark of neoplastic cell metamorphoses. We found that the expression of 210 GT genes taken from 1893 cancer patient samples in The Cancer Genome Atlas (TCGA) microarray data are able to classify six cancers; breast, ovarian, glioblastoma, kidney, colon and lung. The GT gene expression profiles are used to develop cancer classifiers and propose subtypes. The subclassification of breast cancer solid tumour samples illustrates the discovery of subgroups from GT genes that match well against basal-like and HER2-enriched subtypes and correlates to clinical, mutation and survival data. This cancer type glycosyltransferase gene signature finding provides foundational evidence for the centrality of glycosylation in cancer. PMID- 27198046 TI - The effect of zinc supplementation on body composition and hormone levels related to adiposity among children: a systematic review. AB - OBJECTIVE: To provide a comprehensive synthesis of the effects of Zn supplementation on childhood body composition and adiposity-related hormone levels. DESIGN: Five electronic databases were searched for randomized controlled trials of Zn supplementation studies published before 28 February 2015. No statistical pooling of results was carried out due to diversity in study designs. SETTING: Community- or hospital-based, from fourteen developing and developed countries. SUBJECTS: Children and adolescents aged 0 to 10 years. RESULTS: Seven of the fourteen studies reported an overall or subgroup effect of Zn supplementation on at least one parameter of body composition, when determined by anthropometric measurements (increased mid upper-arm circumference, triceps skinfold, subscapular skinfold and mid upper-arm muscle area, and decreased BMI). Three out of the fourteen studies reported increased mean value of total body water estimated by bio-impedance analysis and increased fat-free mass estimated by dual energy X-ray absorptiometry and by total body water. Zn supplementation was associated with increased fat-free mass among stunted children. One study found supplementation decreased leptin and insulin concentrations. CONCLUSIONS: Due to the use of anthropometry when determining body composition, a majority of the studies could not accurately address whether alterations in the fat and/or fat-free mass components of the body were responsible for the observed changes in body composition. The effect of Zn supplementation on body composition is not consistent but may modify fat-free mass among children with pre-existing growth failure. PMID- 27198048 TI - Not all mice are the same: Standardization of animal research data presentation. PMID- 27198049 TI - Corrigendum to "Profiles of HBV DNA in a large population of Chinese patients with chronic hepatitis B: Implications for antiviral therapy" [J Hepatol 2011;54:195-200]. PMID- 27198050 TI - Corrigendum to "Alternatively activated (M2) macrophages promote tumour growth and invasiveness in hepatocellular carcinoma" [J Hepatol 2015;62:607-616]. PMID- 27198051 TI - Erratum to "Clinical implications of basic research in hepatocellular carcinoma" [J Hepatol 2016;64:736-745]. PMID- 27198052 TI - Decrease in total protein level of Bruton's tyrosine kinase during ibrutinib therapy in chronic lymphocytic leukemia lymphocytes. PMID- 27198053 TI - IKZF1 deletion is enriched in pediatric B-cell precursor acute lymphoblastic leukemia patients showing prednisolone resistance. PMID- 27198054 TI - Effectiveness of azacitidine in higher-risk myelodysplastic syndromes. PMID- 27198055 TI - Pharmacologic, Pharmacokinetic, and Clinical Assessment of Illicitly Used gamma Hydroxybutyrate. AB - gamma-Hydroxybutyrate (GHB) is a common drug of abuse and poses important health risks to users in the form of respiratory, cardiovascular, mental, or traumatic adverse events. GHB has non-dose-proportional effects and pharmacologic effects such as sedation and retrograde amnesia, which can incapacitate people targeted for assault. It has Krebs cycle metabolism, rapid clearance, relative hydrophilicity, and unique drug interactions. Promptly seeking medical attention during intentional or inadvertent overdose is critical to survival, as is prompt supportive care once medical personnel are alerted. People drugged before assault also need to promptly notify authorities because the period to detect the drug in the urine or blood is brief and the ultimate metabolites are carbon dioxide and water. After acute treatment has passed, withdrawal could be severe in chronic abusers that could harm the patient directly or drive them back into reuse. PMID- 27198056 TI - 'Not on the radar': dentists' perspectives on the oral health care of dependent older people. AB - OBJECTIVES: We explored the following research questions: (i) what challenges do dentists face when providing oral health care to dependent older adults; and (ii) to overcome those challenges, what recommendations would dentists providing care give those planning and implementing oral health policy and services for dependent older adults? BACKGROUND: The dentate older population is steadily increasing, and about half will end up in residential care, where dental caries rates over time are at least twice as great as those observed elsewhere. MATERIALS AND METHODS: A qualitative study was used, with semi-structured interviews conducted by a single interviewer. Dental examiners in a recent national survey of oral health in dependent older people in New Zealand were interviewed about their experiences and perspectives of that. RESULTS: The challenges participants identified stemmed from three areas - the patient, the care facility and the oral health sector. To address those challenges, the participants recommended actions at the patient, system and sector levels. Each of the challenges and recommendations had a number of subthemes. Overall, the dentists felt that it is a very complex situation urgently requiring policy development, cross-sectoral collaboration and upskilling of the dental profession, carers, the private sector and the State to ensure a care environment which supports achieving and maintaining oral health among frail elders. CONCLUSIONS: Urgent attention to frail older New Zealanders' oral health is needed. Such attention needs to focus on not only the narrow dental clinical preventive and therapeutic implications of those needs, but also on the broader health system and policy development challenges. PMID- 27198057 TI - Peer-counseling for women newly diagnosed with breast cancer: A randomized community/research collaboration trial. AB - BACKGROUND: We conducted a randomized controlled trial of peer-counseling for newly diagnosed breast cancer (BC) patients as a community/research collaboration testing an intervention developed jointly by a community-based-organization serving women with cancer and university researchers. METHODS: We recruited 104 women newly diagnosed with BC at any disease stage. Prior to randomization, all received a one-time visit with an oncology nurse who offered information and resources. Afterwards, we randomized half to receive a match with a Navigator with whom they could have contact for up to 6 months. We recruited, trained, and supervised 30 peer counselors who became "Navigators." They were at least one year post-diagnosis with BC. Controls received no further intervention. We tested the effect of intervention on breast-cancer-specific well-being and trauma symptoms as primary outcomes, and several secondary outcomes. In exploratory analyses, we tested whether responding to their diagnosis as a traumatic stressor moderated outcomes. RESULTS: We found that, compared with the control group, receiving a peer-counseling intervention significantly improved breast-cancer specific well-being (p=0.01, Cohen's d=0.41) and maintained marital adjustment (p=0.01, Cohen's d=0.45) more effectively. Experiencing the diagnosis as a traumatic stressor moderated outcomes: those with a peer counselor in the traumatic stressor group improved significantly more than controls on well-being, trauma and depression symptoms, and cancer self-efficacy. CONCLUSIONS: Having a peer counselor trained and supervised to recognize and work with trauma symptoms can improve well-being and psychosocial morbidity during the first year following diagnosis of BC. Cancer 2016;122:2408-2417. (c) 2016 American Cancer Society. PMID- 27198058 TI - Defect of the mitochondrial DNA hypervariable region as a risk factor for canine mammary tumour. AB - The aim of this study was to identify mutations in the hypervariable region of mitochondrial DNA in canine mammary tumours and to determine their association with the process of neoplastic transformation. A total of 93 biological samples, including blood as well as normal and neoplastic tissue samples from 31 dogs with diagnosed malignant canine mammary tumours were analysed. DNA extraction, amplification and sequencing of the D-loop as well as bioinformatic and statistical analyses were performed. In the mitochondrial D-loop sequence, 26 polymorphic loci and 5 mutations were identified. For the first time, D-loop length heteroplasmy was detected in dogs with mammary tumours. The malignancy grade exerted no effect on the presence of nucleotide changes. A statistically significant association between the presence of mutations and polymorphisms and the size of dogs was demonstrated. The 100% frequency of length heteroplasmy may imply that this is a hotspot mutation of canine mammary tumour. PMID- 27198059 TI - Genetic incorporation of 1,2-aminothiol functionality for site-specific protein modification via thiazolidine formation. AB - Here we report a new site-specific conjugation strategy to modify proteins via thiazolidine ligation. Proteins harbouring a 1,2-aminothiol moiety introduced by amber codon suppression technology could be modified chemoselectively with aldehyde-functionalized reagents, such as a biotin-labeled peptide or ubiquitin, under mild conditions to yield homogeneous biotinylated or ubiquitinated products. PMID- 27198060 TI - Physical activity and screen use policy and practices in childcare: results from a survey of early childhood education services in New Zealand. AB - OBJECTIVE: To investigate written policies, equipment, strategies and barriers to children's activity in early childhood education settings, including participation in health promotion programs and reported time children spend in active play and using screens while in care. METHODS: Cross-sectional online survey of licensed childcare services in Auckland and Waikato. Policies were scored using a validated tool (WellCCAT-NZ). Results were analysed using descriptive statistics and multivariate regression. RESULTS: Managers, head teachers or similar from 237 services completed the survey (28% of invited services). Of these, 35% had a written activity policy; most policies scored low on the WellCCAT-NZ. Comprehensive and strongly worded policies were associated with a lower adult-to-child ratio (p=0.03, adjusted for ECE characteristics). No policies addressed screen use. Children were reported to have teacher-led activity 80 minutes/day, and child-led activity five hours/day (indoor and outdoor). Children watched television daily in 2% and weekly in 11% the services; and used computers daily in 11% and weekly in 22% of services. Fewer than half of services participated in health promotion programs with a physical activity component. CONCLUSIONS: Childcare services reported having adequate equipment, space and time for physical activity of children; however, there are low participation rates in activity programs and a notable absence of written policy. PMID- 27198061 TI - Metal-catalyzed cycloisomerization as a powerful tool in the synthesis of complex sesquiterpenoids. AB - Covering: up to 2015Sesquiterpenoids are consistently attracting the interest of the scientific community due to their promising clinical profile as therapeutic agents. Cycloisomerization of enynes and dienes is a powerful tool in the hands of organic chemists to access them. In the last 20 years the field has witnessed remarkable advances, especially by revealing the capability of platinum and gold complexes to initiate such reactions. Nowadays, cycloisomerizations continue to enrich our knowledge with atom-economical routes and impressive cascades to reach more complex molecules. The current review covers the basic mechanistic aspects of metal catalysis in cycloisomerization reactions and their progress to the synthesis of selected complex sesquiterpenoids. PMID- 27198064 TI - Markedly different adsorption behaviors of gas molecules on defective monolayer MoS2: a first-principles study. AB - Sulfur vacancy (SV) is one of the most typical defects in two-dimensional monolayer MoS2, leading to reactive sites. We presented a systematic study of the adsorption behaviors of gas molecules, CO2, N2, H2O, CO, NH3, NO, O2, H2 and NO2, on monolayer MoS2 with single SV by first-principles calculations. It was found that CO2, N2 and H2O molecules physisorbed at the proximity of single SV. Our adsorption energy calculations and charge transfer analysis showed that the interactions between CO2, N2 and H2O molecules and defective MoS2 are stronger than the cases of CO2, N2 and H2O molecules adsorbed on pristine MoS2, respectively. The defective MoS2 based gas sensors may be more sensitive to CO2, N2 and H2O molecules than pristine MoS2 based ones. CO, NO, O2 and NH3 molecules were found to chemisorb at the S vacancy site and thus modify the electronic properties of defective monolayer MoS2. Magnetism was induced upon adsorption of NO molecules and the defective states induced by S vacancy can be completely removed upon adsorption of O2 molecules, which may provide some helpful information for designing new MoS2 based nanoelectronic devices in future. The H2 and NO2 molecules were found to dissociate at S vacancy. The dissociation of NO2 molecules resulted in O atoms located at the S vacancy site and NO molecules physisorbed on O-doped MoS2. The calculated results showed that NO2 molecules can help heal the S vacancy of the MoS2 monolayer. PMID- 27198065 TI - Gold-catalyzed [4+3] and [4+4]-annulation reactions of t-butyl propiolate derivatives with epoxides and oxetanes for the construction of 1,4-dioxepane and 1,5-dioxocane cores. AB - Gold-catalyzed [4+n]-annulations (n = 3, 4) of tert-butyl propiolate derivatives with epoxides or oxetanes proceed smoothly to yield seven- or eight-membered oxacyclic products efficiently. In the context of the [4+3]-annulations, product analysis reveals a retention of stereochemistry upon the intramolecular SN2 attack of an epoxide. We also report the [4+5]-annulation between one tert-butyl propiolate and gamma-lactol, to manifest the utility toward medium-sized rings. PMID- 27198063 TI - In planta chemical cross-linking and mass spectrometry analysis of protein structure and interaction in Arabidopsis. AB - Site-specific chemical cross-linking in combination with mass spectrometry analysis has emerged as a powerful proteomic approach for studying the three dimensional structure of protein complexes and in mapping protein-protein interactions (PPIs). Building on the success of MS analysis of in vitro cross linked proteins, which has been widely used to investigate specific interactions of bait proteins and their targets in various organisms, we report a workflow for in vivo chemical cross-linking and MS analysis in a multicellular eukaryote. This approach optimizes the in vivo protein cross-linking conditions in Arabidopsis thaliana, establishes a MudPIT procedure for the enrichment of cross-linked peptides, and develops an integrated software program, exhaustive cross-linked peptides identification tool (ECL), to identify the MS spectra of in planta chemical cross-linked peptides. In total, two pairs of in vivo cross-linked peptides of high confidence have been identified from two independent biological replicates. This work demarks the beginning of an alternative proteomic approach in the study of in vivo protein tertiary structure and PPIs in multicellular eukaryotes. PMID- 27198062 TI - Novel positive allosteric modulators of GABAA receptors with anesthetic activity. AB - GABAA receptors are the main inhibitory neurotransmitter receptors in the brain and are targets for numerous clinically important drugs such as benzodiazepines, anxiolytics and anesthetics. We previously identified novel ligands of the classical benzodiazepine binding pocket in alpha1beta2gamma2 GABAA receptors using an experiment-guided virtual screening (EGVS) method. This screen also identified novel ligands for intramembrane low affinity diazepam site(s). In the current study we have further characterized compounds 31 and 132 identified with EGVS as well as 4-O-methylhonokiol. We investigated the site of action of these compounds in alpha1beta2gamma2 GABAA receptors expressed in Xenopus laevis oocytes using voltage-clamp electrophysiology combined with a benzodiazepine site antagonist and transmembrane domain mutations. All three compounds act mainly through the two beta+/alpha- subunit transmembrane interfaces of the GABAA receptors. We then used concatenated receptors to dissect the involvement of individual beta+/alpha- interfaces. We further demonstrated that these compounds have anesthetic activity in a small aquatic animal model, Xenopus laevis tadpoles. The newly identified compounds may serve as scaffolds for the development of novel anesthetics. PMID- 27198066 TI - Advances in the evaluation of canine renal disease. AB - Many recent advances in the evaluation of dogs with kidney disease have improved our diagnostic algorithms and have impacted our therapeutic strategies. Non invasive techniques, such as urinary and serologic biomarker evaluation, can help a clinician diagnose and treat a patient that cannot undergo a renal biopsy for clinical or financial reasons. Some biomarkers might help localize the affected structure (glomerulus vs. tubule) and indicate the type or severity of injury present. Although more research is needed, studies indicate that some biomarkers (e.g. urine protein to creatinine ratio and urinary immunoglobulins) can be useful in predicting adverse outcomes. Importantly, the sensitivity and specificity of biomarkers for renal injury should be established and clinicians need to understand the limitations of these assays. If a renal biopsy is performed, then it should be evaluated by a specialty diagnostic service with expertise in nephropathology. A panel of special stains, immunofluorescence for the detection of immunoglobulins and complement factors, and transmission electron microscopy can be routinely employed in cases of glomerular disease. These advanced diagnostics can be used to detect immune deposits in order to definitively diagnose immune complex mediated glomerular disease. Integrating the results of biomarker assays and comprehensive renal biopsy evaluation, the clinician can make informed therapeutic decisions, such as whether or not to immunosuppress a patient. PMID- 27198067 TI - Periodically pulsed wet annealing approach for low-temperature processable amorphous InGaZnO thin film transistors with high electrical performance and ultrathin thickness. AB - In this paper, a simple and controllable "wet pulse annealing" technique for the fabrication of flexible amorphous InGaZnO thin film transistors (a-IGZO TFTs) processed at low temperature (150 degrees C) by using scalable vacuum deposition is proposed. This method entailed the quick injection of water vapor for 0.1 s and purge treatment in dry ambient in one cycle; the supply content of water vapor was simply controlled by the number of pulse repetitions. The electrical transport characteristics revealed a remarkable performance of the a-IGZO TFTs prepared at the maximum process temperature of 150 degrees C (field-effect mobility of 13.3 cm(2) V(-1) s(-1); Ion/Ioff ratio ~ 10(8); reduced I-V hysteresis), comparable to that of a-IGZO TFTs annealed at 350 degrees C in dry ambient. Upon analysis of the angle-resolved x-ray photoelectron spectroscopy, the good performance was attributed to the effective suppression of the formation of hydroxide and oxygen-related defects. Finally, by using the wet pulse annealing process, we fabricated, on a plastic substrate, an ultrathin flexible a IGZO TFT with good electrical and bending performances. PMID- 27198068 TI - Hospital Surgical Volumes and Mortality after Coronary Artery Bypass Grafting: Using International Comparisons to Determine a Safe Threshold. AB - OBJECTIVE: To estimate a safe minimum hospital volume for hospitals performing coronary artery bypass graft (CABG) surgery. DATA SOURCE: Hospital data on all publicly funded CABG in five European countries, 2007-2009 (106,149 patients). DESIGN: Hierarchical logistic regression models to estimate the relationship between hospital volume and mortality, allowing for case mix. Segmented regression analysis to estimate a threshold. FINDINGS: The 30-day in-hospital mortality rate was 3.0 percent overall, 5.2 percent (95 percent CI: 4.0-6.4) in low-volume hospitals, and 2.1 percent (95 percent CI: 1.8-2.3) in high-volume hospitals. There is a significant curvilinear relationship between volume and mortality, flatter above 415 cases per hospital per year. CONCLUSIONS: There is a clear relationship between hospital CABG volume and mortality in Europe, implying a "safe" threshold volume of 415 cases per year. PMID- 27198069 TI - Gelsolin amyloid angiopathy causes severe disruption of the arterial wall. AB - Hereditary gelsolin amyloidosis (HGA) is a dominantly inherited systemic disease reported worldwide. HGA is characterized by ophthalmological, neurological, and dermatological manifestations. AGel amyloid accumulates at basal lamina of epithelial and muscle cells, thus amyloid angiopathy is encountered in nearly every organ. HGA patients have cardiovascular, hemorrhagic, and potentially vascularly induced neurological problems. To clarify pathomechanisms of AGel angiopathy, we performed histological, immunohistochemical, and electron microscopic analyses on facial temporal artery branches from 8 HGA patients and 13 control subjects. We demonstrate major pathological changes in arteries: disruption of the tunica media, disorganization of vascular smooth muscle cells, and accumulation of AGel fibrils in arterial walls, where they associate with the lamina elastica interna, which becomes fragmented and diminished. We also provide evidence of abnormal accumulation and localization of collagen types I and III and an increase of collagen type I degradation product in the tunica media. Vascular smooth muscle cells appear to be morphologically and semi-quantitatively normal, only their basal lamina is often thickened. In conclusion, angiopathy in HGA results in severe disruption of arterial walls, characterized by prominent AGel deposition, collagen derangement and severe elastolysis, and it may be responsible for several, particularly hemorrhagic, disease manifestations in HGA. PMID- 27198070 TI - Topical delivery of 4-hexylresorcinol promotes wound healing via tumor necrosis factor-alpha suppression. AB - OBJECTIVE: The objective of this study was to evaluate (1) the effect of 4 hexylresorcinol (4HR) application on TNF-alpha expression in RAW264.7 cells and (2) the effect of 4HR ointment on burn wound healing in a rat burn wound model. MATERIALS AND METHODS: RAW264.7 cells were cultured in the presence of different concentrations of 4HR, and the attached cells were sampled for western blot analysis at each time point. Animal studies were conducted on male Wistar rats (n=24). Three treatment groups were evaluated in this study: (1) treatment with ointment alone (negative control), (2) treatment with ointment containing 0.2wt% 4HR, and (3) treatment with ointment containing 2wt% 4HR. For the assessment of wound healing, digital photographs were taken at 1, 5, and 14 days. Animals were sacrificed at 1, 5, and 14 days for histological examination or ELISA analysis. RESULTS: Western blot analysis showed that TNF-alpha protein levels were reduced following treatment with 4HR at concentrations between 1 and 10MUg/mL. In animal studies, the average denuded area 14 days after burn was smaller in the 2wt% 4HR treatment group compared with the control group (P=0.022). Immunohistochemical analysis revealed lower TNF-alpha expression in the 2wt% 4HR treatment group compared with the control group 14 days after burn (P=0.027). CONCLUSION: 4HR reduced TNF-alpha expression in RAW264.7 cells and in the burn wounds of rats. Burn wounds dressed with ointment containing 4HR also exhibited rapid epithelization and collagen regeneration. PMID- 27198071 TI - Photoreaction of adsorbed diiodomethane: halide effects of a series of neutral palladium(ii) coordination cages. AB - A series of Pd6L4-type neutral coordination cages, [Pd6X12L4] (X(-) = Cl(-) and Br(-)), are constructed via self-assembly of (COD)PdCl2 and K2PdBr4 with C3 symmetric N,N',N''-tris(2-pyridinylmethyl)-1,3,5-benzenetricarboxamide (L), respectively. The iodide analogue [Pd6I12L4] is smoothly synthesized from [Pd6Br12L4] in the presence of CH2I2 under mild conditions. The replacement of bromide to iodide in the nanocage system represents a landmark achievement in synthetic-methodology development. The CH2I2 molecules are adsorbed in the order [Pd6I12L4] > [Pd6Br12L4] > [Pd6Cl12L4] and in the "like-attracts-like" pattern, presumably owing to the van der Waals force. Irradiation of [Pd6I12L4].3.5CH2I2 with 1-methylcyclohexene in chloroform at 350 nm preferentially affords the cyclopropanation product. PMID- 27198072 TI - Pregnancy Loss in Dairy Cattle: Relationship of Ultrasound, Blood Pregnancy Specific Protein B, Progesterone and Production Variables. AB - Objectives were to determine associations between percentage pregnancy loss (PPL) in dairy cattle and: (i) pregnancy diagnosis by ultrasonography; (ii) pregnancy diagnosis by serum pregnancy-specific protein B (PSPB) concentrations, with or without serum progesterone concentrations; and (iii) production and environmental factors. This study included 149 822 pregnancy diagnoses conducted over 13 years in Holstein-Friesian cows in Hungarian dairy herds. The following were determined: PPL in cows diagnosed pregnant by transrectal ultrasonography 29-42 days after artificial insemination (AI; n = 11 457); PPL in cows diagnosed pregnant by serum PSPB 29-35 days after AI (n = 138 365); and PPL and its association with serum progesterone concentrations, PSPB and production/environmental variables. The definition of PPL was percentage of cows initially diagnosed pregnant based on ultrasonography or PSPB, but not pregnant when examined by transrectal palpation 60 -70 days after AI. The PPL was lower (p < 0.001) in cows following ultrasonographic vs PSPB diagnosis of pregnancy at 29 35 days (8.1 vs 19.3%, respectively), but was higher in cows following ultrasonographic pregnancy diagnosis on 29-35 vs 36-42 days (8.1 vs 7.1%, respectively, P < 0.05). Furthermore, 72.9% of pregnancies with ultrasound detected morphological abnormalities resulted in pregnancy loss. As a subset of PSPB data, a fully quantitative PSPB assay was used for 20 430 samples; PPL in cows with a high PSPB concentration (>1.1 ng/ml) was lowest (15.0%), whereas cows with low concentrations of both PSPB and progesterone (0.6-1.1 and <2 ng/ml, respectively) had the highest PPL (76.3%; p < 0.0001). Furthermore, PPL was higher in cows with advanced parity and with high milk production, when ambient temperatures were high, although body condition score (BCS) had no effect on PPL. Finally, there were no significant associations between serum PSPB and environmental temperatures or number of post-partum uterine treatments. PMID- 27198073 TI - [Pharmacological treatment of bipolar disorder in children and adolescents]. AB - OBJECTIVE: To review the options for acute and maintenance pharmacological treatment of bipolar disorder in children and adolescents. METHODS: A comprehensive literature review of randomized clinical trials and open-label studies was conducted. RESULTS: Published data from randomized controlled trials show that antipsychotics are significantly more effective than mood stabilizers in the treatment of manic or mixed episodes. Few data are available related to the treatment of depressive episodes. No trials of selective serotonin reuptake inhibitors have been conducted. Only open trials suggest that lithium and lamotrigine may be effective, whereas quetiapine did not demonstrate efficacy relative to placebo in two studies. Studies regarding the effectiveness of antipsychotics and mood stabilizers for the comorbid disorders are also few and inconclusive. Although long-term treatment is a core aspect of the management of children and adolescents with bipolar disorder, there is a lack of consistent efficacy data. If non-controlled trials suggest that lithium, lamotrigine, quetiapine, ziprazidone, and the combination of risperidone and divalproex or lithium may be useful in some conditions, only aripiprazole has shown efficacy relative to placebo for long-term symptom reduction and relapse prevention. Safety data show that the most frequently reported adverse events in children and adolescents treated with mood stabilizers are gastrointestinal and neurological, whereas use of antipsychotics is mainly related to weight gain and sedation. Lastly, while results from studies having evaluated the impact of pharmacological treatment on neuropsychological functioning are inconsistent, some of them nevertheless suggest that treatment with mood stabilizers may be associated with specific impairments. CONCLUSION: Despite recent developments in identifying effective pharmacological interventions, numerous critical gaps remain. PMID- 27198074 TI - [Postictal psychoses: Clinical and neurobiological findings]. AB - Psychosis in epilepsy can be categorized in relation to seizures in two main categories: interictal psychosis and postictal psychosis. Postictal psychosis (PIP) is a specific syndrome in relation to seizure activity: a clear temporal relation exists between the psychotic state of sudden onset and a precipitating bout of complex partial or generalized seizures. However, this very specific syndrome is not included as such within the DSM-5, and PIP belongs to the category "Psychotic disorder due to another medical condition". Diagnostic criteria are: (1) episode of psychosis within 1 week after a seizure(s); (2) psychosis lasts more than 15hours and less than 2 months; (3) delusions, hallucinations in clear consciousness, bizarre, or disorganized behavior, formal thought disorder, or affective changes; and (4) no evidence AED toxicity, non convulsive status epilepticus, recent head trauma, alcohol, or drug intoxication or withdrawal, prior chronic psychotic disorder. The presence of a lucid interval between the last seizure and start of changes rules out a simple postictal delirium. The outcome is characterized by a remission of the psychotic symptoms over several days (mean: 1 week), with or without any treatment. Prepsychotic EEG abnormalities persist during the psychosis. Risk factors for PIP include: long standing localization-related epilepsy, extratemporal onset, bilateral epileptiform activity, secondary generalization, slowing of the EEG background activity and personal or family history of psychiatric disorders. Brain MRI frequently shows structural abnormalities. Several functional neuroimaging studies have shown hyperperfusion in various cerebral regions during PIP, suggesting an excessive activation of particular structures of the brain rather than a postictal depression of cerebral activity. Implanted electrode studies have shown that the EEG correlate of psychotic symptoms differs from the ictal EEG correlate of epileptic seizures. The value of antipsychotic treatment in PIP requires further studies. Despite their role in symptomatic relief, there is no clear effect of neuroleptics on duration or prognosis of PIP. Different combinations of pharmaceutical interventions can be tried on a case by case basis: (1) oral administration of benzodiazepine; (2) combined oral administration of benzodiazepine and atypical neuroleptics; (3) intramuscular administration of dopamine-blockers for rapid tranquilization of violent or agitated patients. The notion that neuroleptic drugs lower the seizure threshold has no clinical significance: there is no evidence that antipsychotic drugs increase seizure frequency in epileptic patients treated with antiepileptic drugs. PMID- 27198075 TI - [Psychopathology related to women pubertal precocity]. AB - INTRODUCTION: Puberty is a developmental process characterized by hormonal and physical changes leading to the ability of reproduction. Precocious puberty, especially in girls, has been associated with an increased incidence of emotional and behavioral problems. Adolescence is a life stage influenced both by the biological changes of puberty and the emergence of new social challenges. In individuals facing these developmental issues at a younger age than expected, the exposure to internal and external stress factors may be greater than in other young people. METHODS: This narrative review provides an overview of psychopathology associated with precocious puberty in order to raise awareness of clinicians dealing with adolescents at risk for adverse behavioral and emotional outcomes. Developmental challenges of standard puberty and adolescence will be outlined before a more detailed description of recent findings from clinical and epidemiological studies. Putative mechanisms underlying the association between precocious puberty and psychopathology will also be discussed. RESULTS: Epidemiological studies have shown that an early onset of puberty in girls is associated with an earlier onset of sexuality, an earlier age of first birth and a lesser professional qualification regardless of cognitive abilities and socio economic status. In both population studies and clinical cohorts, girls with an early age of puberty or in treatment for precocious puberty have more disruptive behavior disorders such as conduct disorders, more substance abuse disorders and delinquent behavior compared to their standard developing peers. Precocious puberty and behavioral problems may have common genetic and environmental risk factors. In young people with conduct disorders and early puberty, findings have emphasized the role of non-shared environmental factors. Low birth weight, obesity, exposure to endocrine-disrupting chemicals and adoption are potentially shared between both conditions. Early puberty in girls is also associated with psychosocial stressors and at-risk environments. The early development of secondary sexual characteristics in girls attracts older and more deviant peers, raising probability of sexual contacts but also of drug use and of a disengagement in school activities. Adolescence is the life stage during which prevalence of depressive disorders rises significantly, especially in girls. Hormonal changes and increase of the Body Mass Index leading to dissatisfaction with body image, have been put forward to explain this trend. Psychosocial challenges (emerging sexuality, instability of identity and social role) are other sources of stress at this particular period of life characterized by emotional hyper-reactivity. These stressors may have greater impact in young people showing a discrepancy between physical and affective maturation. Follow-up studies have shown that emotional and behavioral problems tend to lessen with time. Nevertheless, a heightened risk of depressive disorder remains in girls having had an early onset of puberty when other risk factors co-exist. CONCLUSION: Early puberty, especially in girls, has been associated with a number of emotional and behavioral symptoms and difficulties in adaptive functioning. Even though these adverse outcomes seem to lessen with time, heightened risk for depression and negative impact on socio-professional outcomes persist in subjects with other risk factors. The impact of treatment of precocious puberty on psycho behavioral outcomes is currently unknown. However, clinicians should be aware that the social and emotional challenges these adolescents with atypical pubertal development have to face put them at risk for psychopathology and are potentially accessible to preventive actions. PMID- 27198076 TI - [Cas report: Affective symptoms and emerging psychotic disorder in adolescents]. PMID- 27198077 TI - Harnessing Poly(ionic liquid)s for Sensing Applications. AB - The interest in poly(ionic liquid)s for sensing applications is derived from their strong interactions to a variety of analytes. By combining the desirable mechanical properties of polymers with the physical and chemical properties of ILs, new materials can be created. The tunable nature of both ionic liquids and polymers allows for incredible diversity, which is exemplified in their broad applicability. In this article we examine the new field of poly(ionic liquid) sensors by providing a detailed look at the current state-of-the-art sensing devices for solvents, gases, biomolecules, pH, and anions. PMID- 27198080 TI - Does admission to a specialist geriatric medicine ward lead to improvements in aspects of acute medical care for older patients with dementia? AB - OBJECTIVE: The objective of this study is to clarify if admission to a specialist geriatric medicine ward leads to improvements in aspects of acute medical care for patients with dementia. METHODS: We analysed combined data involving 900 patients from the Irish and Northern Irish audits of dementia care. Data on baseline demographics, admission outcomes, clinical aspects of care, multidisciplinary assessment and discharge planning processes were collected. RESULTS: Less than one-fifth of patients received their inpatient care on a specialist geriatric medicine ward. Patients admitted to a geriatric medicine ward were less likely to undergo a formal assessment of mobility compared with those in non-geriatric wards (119/143 (83%) vs 635/708 (90%), odds ratio (OR) = 0.57 (0.35 to 0.94)) and were more likely to receive newly prescribed antipsychotic medication during the admission (27/54 (50%) vs 95/2809 (36%), OR = 1.95 (1.08 to 3.51)). Patients admitted to a geriatric medicine ward were more likely to have certain aspects of discharge planning initiated, including completion of a single plan for discharge (78/118 (66%) vs 275/611 (45%), OR = 2.38 (1.58 to 3.60)). Surgical wards performed more poorly on certain aspects including having a named discharge co-ordinator (32/71, 45%) and documentation of decisions regarding resuscitation status (18/95, 19%). CONCLUSION: Relatively low numbers of patients with dementia received care on a specialist geriatric medicine ward. There appears to be a more streamlined discharge planning process in place on these wards, but they did not perform as well as one would expect in certain areas, such as compliance with multidisciplinary assessment and antipsychotic prescribing. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27198079 TI - Activities Patients and Nurses Undertake to Promote Patient Participation. AB - PURPOSE: To describe and understand activities patients and nurses undertake to enact patient participation in nursing care. DESIGN: This observational study was conducted on two medical units at a public hospital in Australia. Twenty-eight nurse-patient dyads were observed for at least 4 hr. Data were collected from November 2013 to February 2014. METHODS: Field notes were collected and were analyzed both inductively and deductively. FINDINGS: Nurse-patient interactions promoted patient participation through dialogue and knowledge sharing. Less evident was patient involvement in planning or self-care. Nurses exerted control over patient care, which influenced the extent of patient participation. CONCLUSIONS: Patient participation appears to be difficult to enact. Nurses' controlling approach, influenced by organizational issues, was in conflict with a patient-centered approach to care. Nurse-patient communication is one aspect of patient-centered care enacted more frequently. CLINICAL RELEVANCE: Nurses may benefit from strategies at the individual and organizational level to enhance their patient-centered practices. Fostering nurses' communication may enhance patient-centered practices in hospitals. PMID- 27198078 TI - Sunburn and sun-protective behaviors among adults with and without previous nonmelanoma skin cancer (NMSC): A population-based study. AB - BACKGROUND: Individuals with previous nonmelanoma skin cancer (NMSC) are at increased risk for subsequent skin cancer, and should therefore limit ultraviolet exposure. OBJECTIVE: We sought to determine whether individuals with previous NMSC engage in better sun protection than those with no skin cancer history. METHODS: We pooled self-reported data (2005 and 2010 National Health Interview Surveys) from US non-Hispanic white adults (758 with and 34,161 without previous NMSC). We calculated adjusted prevalence odds ratios (aPOR) and 95% confidence intervals (CI), taking into account the complex survey design. RESULTS: Individuals with previous NMSC versus no history of NMSC had higher rates of frequent use of shade (44.3% vs 27.0%; aPOR 1.41; 95% CI 1.16-1.71), long sleeves (20.5% vs 7.7%; aPOR 1.55; 95% CI 1.21-1.98), a wide-brimmed hat (26.1% vs 10.5%; aPOR 1.52; 95% CI 1.24-1.87), and sunscreen (53.7% vs 33.1%; aPOR 2.11; 95% CI 1.73-2.59), but did not have significantly lower odds of recent sunburn (29.7% vs 40.7%; aPOR 0.95; 95% CI 0.77-1.17). Among those with previous NMSC, recent sunburn was inversely associated with age, sun avoidance, and shade but not sunscreen. LIMITATIONS: Self-reported cross-sectional data and unavailable information quantifying regular sun exposure are limitations. CONCLUSION: Physicians should emphasize sunburn prevention when counseling patients with previous NMSC, especially younger adults, focusing on shade and sun avoidance over sunscreen. PMID- 27198081 TI - Admission of medical patients from the emergency department: An assessment of the attitudes, perspectives and practices of internal medicine and emergency medicine trainees. AB - OBJECTIVE: We sought to obtain a deeper understanding of the differing needs and expectations of inpatient and ED medical staff regarding the admission process for medical patients. DESIGN: Online questionnaire regarding their attitudes to and perceptions of various aspects of the admission process was used. SETTING: The setting is a tertiary 640-bed adult hospital with over 60 000 ED presentations per year and an inpatient admission rate of 30%. RESULTS: A total of 42 out of 56 (75%) internal medical trainees (IMT) felt that the ED admission workup standard was lower or much lower than the inpatient standard; however, 10 of 16 (62.5%) ED trainees (EDT) thought it was similar (P = 0.009). Regarding why IMT order additional tests in the ED, the major reason supported by IMT was to 'identify or exclude urgent pathology' (53/56, 96.4%); however, this reason ranked only fifth for EDT (2/16, 12.5%) who ranked 'to ensure nothing was missed' (12/15, 80%) first. A total of 24 out of 56 (42.8%) IMT felt that if ED admissions were enacted without IMT review, inappropriate admissions to hospital would occur regularly although only one of 16 EDT (6.3%) agreed (P = 0.025). A total of 14 out of 16 (87.5%) EDT but only 16 of 56 (23.2%) IMT were comfortable with admissions occurring without inpatient review in the ED (P < 0.001). The top two perceived barriers to a smooth and timely admission process for IMT were patient instability (34/43, 79.1%) and inadequate ED workup (37/49, 75.5%); for EDT, they were excessive IMT workload (11/14, 78.6%) and referral close to the end of an IMT shift (7/11, 63.6%). CONCLUSION: Substantial barriers to more harmonious admission processes exist. A 'paradigm shift' where roles and responsibilities are clear might be required. Defusing tension across the ED inpatient interface should improve efficiency and ensure that patient outcomes remain the focus. PMID- 27198082 TI - miR-30c and semaphorin 3A determine adult neurogenesis by regulating proliferation and differentiation of stem cells in the subventricular zones of mouse. AB - OBJECTIVES: Mechanisms that regulate proliferation of adult neural stem cells are largely unknown. Here, we have investigated the role of microR-30c (miR-30c) and its target, semaphoring 3A (sema3A), in regulating adult neurogenesis and mechanisms underlying this process. MATERIALS AND METHODS: In situ hybridization, immunofluorescence and quantitative real-time PCR were used to assess complementary expression patterns of miR-30c and sema3A in mice. Effects of miR 30c in the subventricular zone (SVZ) were examined by stereotaxic injection of up and down-regulating lentiviruses. 5'-bromo-2'-deoxyuridine labelling was performed to investigate effects of miR-30c and sema3A on adult neurogenesis. Real-time cell assays, morphological analysis and cell cycle measurements were used to reveal the mechanisms by which miR-30c and sema3A regulate adult neurogenesis. RESULTS: Expression of miR-30c negatively correlated with that of sema3A in neurons, and levels of miR-30c and sema3A correlated positively with numbers of newborn cells in the SVZ and rostral migration stream. miR-30c and sema3A affected adult neurogenesis by regulating proliferation and differentiation, as well as cycles of stem cells in the SVZ. CONCLUSIONS: miR-30c and sema3A regulate adult neurogenesis by controlling proliferation and differentiation of stem cells in the SVZ. This finding reveals a novel regulatory mechanism of adult neurogenesis. PMID- 27198083 TI - Inducing optimal substitution between antibiotics under open access to the resource of antibiotic susceptibility. AB - This paper designs a bio-economic model to examine the use of substitute antibiotic drugs (analogs) sold by an industry that has open access to the resource of the antibiotic class's susceptibility (treatment effectiveness). Antibiotics are characterized by different expected recovery rates and production costs, which in conjunction with the class's treatment susceptibility determines their relative effectiveness. Our analysis reveals that the high-quality antibiotic drug loses its comparative advantage over time making the low-quality drug the treatment of last resort in the market equilibrium and the social optimum when antibiotic susceptibility cannot replenish. However, when antibiotic susceptibility is renewable, both antibiotics may be used in the long run, and the comparative advantage of the high-quality drug may be restored in the social optimum that allows lowering infection in the long run. We develop the optimal tax/subsidy scheme that would induce antibiotic producers under open access to behave optimally and account for the social cost of infection and value of antibiotic susceptibility. We show that the welfare loss associated with the uncorrected open-access allocation is highest; when the resource of antibiotic susceptibility is non-renewable, high morbidity costs are incurred by individuals, and low social discount rates apply. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27198084 TI - CatacLysMic specificity when targeting myeloid cells? AB - The antibacterial enzyme lysozyme M (LysM) encoded by the Lyz2 gene is broadly expressed in myeloblasts, macrophages, and neutrophils, and thus has been used for a long time as a cell-specific marker for myeloid cells in mice. In order to delete loxP-site flanked genes in myeloid cells, a Cre-recombinase (Cre) expressing mouse line was created by inserting Cre-coding sequence into the translational start site of the LysM gene. In this issue of the European Journal of Immunology [2016. 46: 1529-1532], Orthgiess et al. verify, with the help of tdTomato and YFP reporter mouse lines, LysM-driven recombination. Unexpectedly, the authors also describe major expression of the tdTomato reporter protein in brain neurons of the central nervous system (CNS), with only a very small percentage of gene recombination in myeloid cells of the brain, called microglia. These findings cause justified concerns regarding the efficient and specific targeting of microglia and peripheral myeloid cells using LysM-Cre mice and should stimulate thoughts on conclusions drawn from past experiments on the diseased CNS employing this Cre/loxP-deleter line. PMID- 27198086 TI - Part I: The Context and Importance of Evidence-Based Health Informatics. PMID- 27198087 TI - The Need for Evidence in Health Informatics. AB - While the use of health IT applications has increased rapidly over past decades, this does not compare strongly with other business sectors. Both reluctance to invest in, and lack of demand to use IT systems may in part be due to lack of robust evidence as to proven benefits. At the same time, the health IT sector has lagged behind other health technology areas in working to, and being expected to work to, robust evidence standards showing benefit and also avoidance of harm. Exacerbating this, limited availability of evidence has perpetuated this misplaced comfort in use of aspiration and expectation rather than evidence in driving investment in health IT applications. Reference back to the core principles drawn from influential thinkers shows the essential centrality of the need for evidence of safety and effectiveness, and for its use relevantly related to context. PMID- 27198088 TI - Evidence-based Health Informatics and the Scientific Development of the Field. AB - We define and discuss the nature of Evidence-based Health Informatics (EBHI), the kind of evidence health informatics researchers must generate to make EBHI a reality, and how we should grade such evidence. We propose adding principle-based evaluation studies to the list of common evaluation study types, and outline how to carry out such studies to generate evidence that will prove useful for establishing EBHI. The main purpose of a principle-based evaluation study is to test the impact on system acceptability, usage or effectiveness of a generalizable system design principle, so we also explore when during the system design process such principles are needed, and which disciplines are most promising as sources of design principles. We conclude with some challenges for EBHI, a list of the benefits of adopting this approach, and a test to ensure that we are advancing in the direction of science, as opposed to pseudoscience. PMID- 27198085 TI - Prevalence and predictors of inadequate patient medication knowledge. AB - OBJECTIVES: To assess medication knowledge in adult patients and to explore its determinants. METHOD: Cross-sectional study. Medication knowledge was the primary outcome and was assessed using a previously validated questionnaire. A multivariate logistic regression analysis was performed to explore the association between medication knowledge and the factors included in the model. RESULTS: Seven thousand two hundred seventy-eight patients participated in the study. 71.9% (n = 5234) (95% CI: 70.9%-73.0%) of the surveyed patients had an inadequate knowledge of the medication they were taking. The dimensions obtaining the highest level of knowledge were the 'medication use process' and 'therapeutic objective of medication'. The items 'frequency' (75.4%), 'dosage' (74.5%) and 'indication' (70.5%) had the highest percentage of knowledge. Conversely, 'medication safety' represented the dimension with the lowest scores, ranging from 12.6% in the item "contraindications" to 15.3% in the item 'side effects'. The odds ratio (OR) of having an inadequate medication knowledge increased for unskilled workers (OR: 1.33; 85% CI:1.00-1.78; P = 0.050), caregivers (OR:1.46; 95% CI:1.18-1.81; P < 0.001), patients using more than one medication (OR: 1.14; 95% CI: 1.00-1.31; P = 0.050) and patients who did not know the name of the medication they were taking (OR: 2.14, 95% CI: 1.71-2.68 P < 0.001). CONCLUSION: Nearly three quarters of the analysed patients had inadequate knowledge regarding the medicines they were taking. Unskilled workers and caregivers were at a higher risk of lacking of medication knowledge. Other factors that correlated with inadequate medication knowledge were the use of more than one drug and not knowing the name of the medication dispensed. PMID- 27198089 TI - Health IT for Patient Safety and Improving the Safety of Health IT. AB - Alongside their benefits health IT applications can pose new risks to patient safety. Problems with IT have been linked to many different types of clinical errors including prescribing and administration of medications; as well as wrong patient, wrong-site errors, and delays in procedures. There is also growing concern about the risks of data breach and cyber-security. IT-related clinical errors have their origins in processes undertaken to design, build, implement and use software systems in a broader sociotechnical context. Safety can be improved with greater standardization of clinical software and by improving the quality of processes at different points in the technology life cycle, spanning design, build, implementation and use in clinical settings. Oversight processes can be set up at a regional or national level to ensure that clinical software systems meet specific standards. Certification and regulation are two mechanisms to improve oversight. In the absence of clear standards, guidelines are useful to promote safe design and implementation practices. Processes to identify and mitigate hazards can be formalised via a safety management system. Minimizing new patient safety risks is critical to realizing the benefits of IT. PMID- 27198090 TI - Part II: Methodological Considerations of Health IT Evaluation. PMID- 27198091 TI - Theoretical Basis of Health IT Evaluation. AB - The focus of this contribution is on the theoretical principles and concepts behind evaluation of IT-based systems, discussing their presuppositions, implications and interrelationships; for instance in relation to a series of issues to consider: terminology for the concepts used as that is a reason for many disputes, bias as that is a common reason for less accuracy and trustworthiness in conclusions, culture as the tacit driver of everything we do and design, constructive evaluation as this has strict time and timing issues, preparing for meta-analyses as that is in the near future, and top-level issues in choice of methodology. Awareness in these respects will lead to avoidance of major pitfalls and perils at evaluation and thereby improve the validity and trustworthiness of an evaluation outcome, supporting the initiative towards evidence-based health informatics. PMID- 27198092 TI - Understanding Stakeholder Interests and Perspectives in Evaluations of Health IT. AB - Appropriately identifying and representing stakeholders' interests and viewpoints in evaluations of health information technology (health IT) is a critical part of ensuring continued progress and innovation in eHealth. This contribution therefore seeks to clarify the principles of stakeholder analysis in an eHealth context. We describe this with reference to a mixed methods national evaluation of ePrescribing systems in English hospitals. We use this evaluation to exemplify the engagement and analytical tools required to ensure a detailed understanding of the issues, challenges and lessons learnt across stakeholder groups. We conclude that this type of approach may support the robustness of evaluations of health IT as well as their longer term impact on innovation in the field. PMID- 27198093 TI - Domains of Health IT and Tailoring of Evaluation: Practicing Process Modeling for Multi-Stakeholder Benefits. AB - This contribution focuses on the heterogeneity and complexity of health information technology services and systems in a multi-stakeholder environment. We propose the perspective of process modeling as a method to break out complexity, represent heterogeneity, and provide tailored evaluation and optimization of health IT systems and services. Two case studies are presented to show how process modeling is needed to fully understand the information flow, thus identifying requirements and specifications for information system re engineering and interoperability; detect process weaknesses thus designing corrective measures; define metrics as a mean to evaluate and ensure system quality; and optimize the use of resources. PMID- 27198094 TI - Evidence-based Health Informatics Frameworks for Applied Use. AB - Health Informatics frameworks have been created surrounding the implementation, optimization, adoption, use and evaluation of health information technology including electronic health record systems and medical devices. In this contribution, established health informatics frameworks are presented. Important considerations for each framework are its purpose, component parts, rigor of development, the level of testing and validation its undergone, and its limitations. In order to understand how to use a framework effectively, it's often necessary to seek additional explanation via literature, documentation, and discussions with the developers. PMID- 27198095 TI - Ensuring the Quality of Evidence: Using the Best Design to Answer Health IT Questions. AB - The quality of logic in a research design determines the value of the results and our confidence regarding the validity of the findings. The purpose of this contribution is to review the principles of research design as they apply to research and evaluation in health IT. We review the architecture of research design, the definitions of cause, sources of bias and confounds, and the importance of measurement as related to the various types of health IT questions. The goal is to provide practitioners a roadmap for making decisions for their own specific study. The contribution is organized around the Threats to Validity taxonomy and explains how different design models address these threats through the use of blocking, factorial design, control groups and time series analysis. The contribution discusses randomized experiments, and includes regression discontinuity designs and various quasi-experimental designs with a special emphasis on how to improve pre/post designs. At the end, general recommendations are provided for improving weaker designs and general research procedures. PMID- 27198096 TI - Mixed Methods: A Paradigm for Holistic Evaluation of Health IT. AB - This contribution offers an overview of the 'third research paradigm', its historical roots and its relevance for health informatics. Using illustrative studies, we explore the concepts of triangulation and integration of quantitative and qualitative data and refute common philosophical objections to mixing different types of knowledge. We consider how the mixed method paradigm relates to two programme design and evaluation frameworks that are important for health informatics: realist evaluation and Theory of Change. We discuss how to manage practical challenges to this approach and explain how mixed method studies support an evidence-based approach to real world policy, planning and investment decisions. PMID- 27198097 TI - Evaluation of People, Social, and Organizational Issues - Sociotechnical Ethnographic Evaluation. AB - Sociotechnical approaches are grounded in theory and evidence-based. They are useful for evaluations involving health information technologies. This contribution begins with an overview of sociotechnical theory and ethnography. These theories concern interactions between technology, its use, people who use or are affected by it, and their organizational and societal situations. Then the contribution discusses planning and designing evaluations, including frameworks and models to focus an evaluation, and methodological considerations for conducting it. Next, ethical issues and further challenges and opportunities are taken up. Concluding case examples, referenced throughout, illustrate how good evaluations provide useful results to help design, implement, and use health information technologies effectively. PMID- 27198098 TI - From Usability Engineering to Evidence-based Usability in Health IT. AB - Usability is a critical factor in the acceptance, safe use, and success of health IT. The User-Centred Design process is widely promoted to improve usability. However, this traditional case by case approach that is rooted in the sound understanding of users' needs is not sufficient to improve technologies' usability and prevent usability-induced use-errors that may harm patients. It should be enriched with empirical evidence. This evidence is on design elements (what are the most valuable design principles, and the worst usability mistakes), and on the usability evaluation methods (which combination of methods is most suitable in which context). To achieve this evidence, several steps must be fulfilled and challenges must be overcome. Some attempts to search evidence for designing elements of health IT and for usability evaluation methods exist and are summarized. A concrete instance of evidence-based usability design principles for medication-related alerting systems is briefly described. PMID- 27198099 TI - Participatory Design, User Involvement and Health IT Evaluation. AB - End user involvement and input into the design and evaluation of information systems has been recognized as being a critical success factor in the adoption of information systems. Nowhere is this need more critical than in the design of health information systems. Consistent with evidence from the general software engineering literature, the degree of user input into design of complex systems has been identified as one of the most important factors in the success or failure of complex information systems. The participatory approach goes beyond user-centered design and co-operative design approaches to include end users as more active participants in design ideas and decision making. Proponents of participatory approaches argue for greater end user participation in both design and evaluative processes. Evidence regarding the effectiveness of increased user involvement in design is explored in this contribution in the context of health IT. The contribution will discuss several approaches to including users in design and evaluation. Challenges in IT evaluation during participatory design will be described and explored along with several case studies. PMID- 27198100 TI - Clinical Simulation as an Evaluation Method in Health Informatics. AB - Safe work processes and information systems are vital in health care. Methods for design of health IT focusing on patient safety are one of many initiatives trying to prevent adverse events. Possible patient safety hazards need to be investigated before health IT is integrated with local clinical work practice including other technology and organizational structure. Clinical simulation is ideal for proactive evaluation of new technology for clinical work practice. Clinical simulations involve real end-users as they simulate the use of technology in realistic environments performing realistic tasks. Clinical simulation study assesses effects on clinical workflow and enables identification and evaluation of patient safety hazards before implementation at a hospital. Clinical simulation also offers an opportunity to create a space in which healthcare professionals working in different locations or sectors can meet and exchange knowledge about work practices and requirement needs. This contribution will discuss benefits and challenges of using clinical simulation, and will describe how clinical simulation fits into classical usability studies, how patient safety may benefit by use of clinical simulation, and it will describe the different steps of how to conduct clinical simulation. Furthermore a case study is presented. PMID- 27198101 TI - Economic Evaluation of Health IT. AB - Economic evaluation in health care supports decision makers in prioritizing interventions and maximizing the available limited resources for social benefits. Health Information Technology (health IT) constitutes a promising strategy to improve the quality and delivery of health care. However, to determine whether the appropriate health IT solution has been selected in a specific health context, its impact on the clinical and organizational process, on costs, on user satisfaction as well as on patient outcomes, a rigorous and multidimensional evaluation analysis is necessary. Starting from the principles of evaluation introduced since the mid-1980s within the Health Technology Assessment (HTA) guidelines, this contribution provides an overview of the main challenging issues related to the complex task of performing an economic evaluation of health IT. A set of necessary key principles to deliver a proper design and implementation of a multidimensional economic evaluation study is described, focusing in particular on the classification of costs and outcomes as well as on the type of economic analysis to be performed. A case study is eventually described to show how the key principles introduced are applied. PMID- 27198102 TI - Health Care Performance Indicators for Health Information Systems. AB - Health Information Systems (HISs) are expected to have a positive impact on quality and efficiency of health care. Rapid investment in and diffusion of HISs has increased the importance of monitoring the adoption and impacts of them in order to learn from the initiatives, and to provide decision makers evidence on the role of HISs in improving health care. However, reliable and comparable data across initiatives in various countries are rarely available. A four-phase approach is used to compare different HIS indicator methodologies in order to move ahead in defining HIS indicators for monitoring effects of HIS on health care performance. Assessed approaches are strong on different aspects, which provide some opportunities for learning across them but also some challenges. As yet, all of the approaches do not define goals for monitoring formally. Most focus on health care structural and process indicators (HIS availability and intensity of use). However, many approaches are generic in description of HIS functionalities and context as well as their impact mechanisms on health care for HIS benchmarking. The conclusion is that, though structural and process indicators of HIS interventions are prerequisites for monitoring HIS impacts on health care outputs and outcomes, more explicit definition is needed of HIS contexts, goals, functionalities and their impact mechanisms in order to move towards common process and outcome indicators. A bottom-up-approach (participation of users) could improve development and use of context-sensitive HIS indicators. PMID- 27198103 TI - Evaluating the Impact of Health IT on Medication Safety. AB - Health IT is becoming an increasingly powerful tool for improving medication safety. While errors may happen at all stages of the medication process, different tools have been developed to support the prescribing process (e.g. computerized prescribing with decision support), the dispensing process (e.g. barcoding or automated dispensing and unit-dose systems), or the administration process (e.g. electronic medication administration records and smart pumps). Health IT can reduce medication error and preventable adverse drug event rates by increasing documentation quality and transparency, enhancing accuracy and correctness of the medication process, and supporting information exchange and interlinking different stages of the medication process. Typical evaluated endpoints comprise process-related outcomes such as number of medication errors, harm-related outcomes such as adverse drug events, or cost-related outcomes. Typical study design to measure effectiveness of health IT in medication safety comprises before-after studies and randomized controlled trials. However, implementation is challenging; it often has a major impact on the overall workflow and such technologies must be carefully introduced and their effects must be closely monitored in order to achieve the desired reductions, as in addition to preventing errors they nearly always introduce new ones. As complex interventions, their impact depends crucially on the real world setting and the implementation details and thus, transferability of study results is variable. PMID- 27198104 TI - Evaluation of Implementation of Health IT. AB - Information systems can only reach their full potential if their implementation is effective, and there is much to be learned as to what makes an "effective" implementation. In light of the substantial investments in Health Information Technology internationally, implementation evaluations are a powerful tool to ensure that technologies are enabled to fulfil their potential in improving care, reducing cost and increasing efficiency. The most salient characteristics of such evaluations are outlined, considering how they can help to assess adoption processes and outcomes through a continuous cycle of scientific enquiry and learning. A brief description surrounding potential theoretical lenses that may be drawn on is given. Issues discussed will be illustrated with the help of a case study on the implementation and adoption of Electronic Health Records in English hospitals. Practical challenges encountered and potential ways to address these during the conduct of health IT implementation evaluations illustrated include: 1) ways to cope with the shifting nature of reality (e.g. changes in local implementation strategies need to be reflected in the methods), 2) the need to examine processes as well as outcomes, 3) researching implementation in context with attention to both local processes and wider (e.g. political) developments, and 4) the pragmatic use of theoretical lenses where different approaches can shed light on different aspects of the implementation and adoption process. PMID- 27198105 TI - Evolving Health IT Systems Evaluation: The Convergence of Health Informatics and HTA. AB - The credibility and reliability of health IT systems as a means of achieving changes towards safer and cost-effective care have been questioned for over two decades due to the lack of methodologically strong evidence. As national level adoption and implementation of health IT are becoming widespread across the EU and globally, but are also being offset by adverse reports, the demands for evidence become more pronounced and the stakes higher. The adaptation of HTA (health technology assessment) methodology as a means to address gaps in health IT evidence production has been proposed repeatedly and tested in the field of telemedicine services. HTA has in many ways run a course parallel to that of health IT, while in certain respects attaining more clear achievements. This contribution investigates aspects of a bilaterally beneficial relation between the two disciplines using three lines of exploration: the methodological goodness of-fit between health IT evaluation and HTA; the solutions each has proposed to the problem of producing high quality evidence in reduced amount of time; and the way each has addressed the strengthened role and position of patients. The analysis demonstrates areas of convergence between health IT and HTA. It also highlights topics which would need to be jointly addressed in the process, such as innovative and high quality data collection and analysis, inclusion of patient reported outcomes and patient safety, and transferability and generalizability of findings. In closing, it takes a glimpse of the challenges emerging as a result of the progress at the cross-roads of medicine, science and technology. PMID- 27198107 TI - Ensuring Evidence-Based Safe and Effective mHealth Applications. AB - The Internet and the digitalization of information have brought big changes in healthcare, but the arrival of smartphones and tablets represent a true revolution and a new paradigm is opened which completely changes our lives. In order to validate the impact of these new technologies in health care, it is essential to have enough clinical studies that validate their impact in wellbeing and healthcare of the patient. Traditional regulatory organisations are still looking for their role in this area. If they follow the classical path of medical devices, we get to a technical, administration and economic collapse. This contribution first presents the main indicators showing the potential of mHealth adoption. It then proposes a classification of mobile health care apps, and presents frameworks for mHealth evaluation. Regulation of mHealth as part of the evaluation process is discussed. Finally, the necessary steps and challenges that have to be taken into account by the industry to prepare the entrance of these technologies into the EU market is analysed. PMID- 27198106 TI - Realizing the Potential of Patient Engagement: Designing IT to Support Health in Everyday Life. AB - Maintaining health or managing a chronic condition involves performing and coordinating potentially new and complex tasks in the context of everyday life. Tools such as reminder apps and online health communities are being created to support patients in carrying out these tasks. Research has documented mixed effectiveness and problems with continued use of these tools, and suggests that more widespread adoption may be aided by design approaches that facilitate integration of eHealth technologies into patients' and family members' daily routines. Given the need to augment existing methods of design and implementation of eHealth tools, this contribution discusses frameworks and associated methods that engage patients and explore contexts of use in ways that can produce insights for eHealth designers. PMID- 27198108 TI - Systematic Reviews and Meta-Analysis of Health IT. AB - This contribution examines how systematic reviews contribute to the evaluation of health IT planning and implementation. It defines and explains the systematic review process and how higher level overviews of health IT can be conducted. A reprise of some of the Cochrane reviews relating to health IT, particularly those conducted for the Cochrane Effective Practice and Organization of Care Group (EPOC), provides examples of the type of question that can be answered (at least in part) by a Cochrane-type systematic review. The contribution also discusses the benefits and limitations of the systematic review process using examples of reviews on telemedicine, nursing records, and home uterine monitoring in pregnancy. PMID- 27198109 TI - Going Beyond Systematic Reviews: Realist and Meta-Narrative Reviews. AB - Health information technologies are complex interventions whose effects differ across contexts. To improve our understanding of the effects of health information technologies, approaches are needed that utilize evidence beyond experimental results in order to provide explanatory answers to how and why a given technology works. The relatively new realist and meta-narrative review approaches are introduced as important methods in synthesising and analysing evidence in the field of health informatics. A common purpose of these two review approaches is to help create a sense of evidence about complex interventions that enables an understanding of how and why they work. A detailed description of the principles and objectives of the two types of reviews is presented. Key steps required to conduct each of the reviews are summarized, and examples of how the review approaches have been applied to topics related to health informatics are provided. Limitations of the two review approaches are discussed. PMID- 27198110 TI - Part III: Ensuring the Relevance and Application of Evidence. PMID- 27198112 TI - Publishing Health IT Evaluation Studies. AB - Progress in science is based on evidence from well-designed studies. However, publication quality of health IT evaluation studies is often low, making exploitation of published evidence within systematic reviews and meta-analysis a challenging task. Consequently, reporting guidelines have been published and recommended to be used. After a short overview of publication guidelines relevant for health IT evaluation studies (such as CONSORT and PRISMA), the STARE-HI guidelines for publishing health IT evaluation studies are presented. Health IT evaluation publications should take into account published guidelines, to improve the quality of published evidence. Publication guidelines, in line with addressing publication bias and low study quality, help strengthening the evidence available in the public domain to enable effective evidence-based health informatics. PMID- 27198111 TI - Quality of Health IT Evaluations. AB - Health IT evaluation studies have often been found to be of limited quality. To address this problem, several guidelines and frameworks have been developed as tools to support improvement of the quality of evaluation studies. In this contribution, we review available guidelines and then present the Good Evaluation Practice Guideline in Health Informatics (GEP-HI) in more detail. GEP-HI is a comprehensive guideline which supports especially planning and execution of a health IT evaluation study. The GEP-HI guideline helps to overcome the quality problems related to weak study planning and methodological study design. We also discuss application of GEP-HI on an evaluation project and discuss the need to publish systematically following the recognised publication guidelines. Finally we discuss the future trend on multi-method evaluation approaches. PMID- 27198114 TI - Evaluation of Health IT in Low-Income Countries. AB - Low and middle income countries (LMICs) bear a disproportionate burden of major global health challenges. Health IT could be a promising solution in these settings but LMICs have the weakest evidence of application of health IT to enhance quality of care. Various systematic reviews show significant challenges in the implementation and evaluation of health IT. Key barriers to implementation include lack of adequate infrastructure, inadequate and poorly trained health workers, lack of appropriate legislation and policies and inadequate financial 333indicating the early state of generation of evidence to demonstrate the effectiveness of health IT in improving health outcomes and processes. The implementation challenges need to be addressed. The introduction of new guidelines such as GEP-HI and STARE-HI, as well as models for evaluation such as SEIPS, and the prioritization of evaluations in eHealth strategies of LMICs provide an opportunity to focus on strategic concepts that transform the demands of a modern integrated health care system into solutions that are secure, efficient and sustainable. PMID- 27198113 TI - Finding, Appraising and Interpreting the Evidence of Health IT. AB - Evidence-based health informatics can be described as a scientific approach to meeting the multiplicity of tasks involved in the development, implementation and sustainability of health information technologies (IT). The practice of evidence based health informatics incorporates methods to help find, appraise and utilise research-based knowledge. The aim of this contribution is to describe the steps of finding, appraising and interpreting the evidence of health IT. It lists major sources of literature in the health field, and highlights a number of considerations for undertaking reviews, drawing on some key landmark reviews that have helped to shape the health informatics discipline. It also considers key issues highlighted by these reviews particularly in regard to the validity of findings, their generalisability and their impact on patient outcomes. The contribution also provides suggestions for tackling the challenge of potential publication bias, and how to deal with heterogeneous findings. PMID- 27198115 TI - Learning, Training and Teaching of Health Informatics and its Evidence for Informaticians and Clinical Practice. AB - A globally agreed well structured framework representing the health informatics discipline's body of knowledge is yet to emerge. Considerable progress has been made towards describing this over the fifty or so years of the discipline's evolution. This contribution explains the need for such a structured body of knowledge from an educational and workforce capacity building perspective. Some examples of how education and training has been provided to date by a few key stakeholders/leaders are given and critical reviews of guideline and competency developments and their applications are presented. This is followed by an explanation of the need for linking health informatics research with education, learning and training strategies and desired future directions to overcome the identified health workforce knowledge and skills gaps are explored. Given the increasingly important role of health IT in health care, and the significant investment being made into Health IT systems and infrastructure, it is illogical not to seriously invest in health workforce capacity building. PMID- 27198117 TI - Appendix. PMID- 27198116 TI - Forward Outlook: The Need for Evidence and for Action in Health Informatics. AB - Evidence-based health informatics (EBHI) is a key concept in the development and deployment of IT systems and applications in an ethical, efficient and effective health system. There is an ever growing body of knowledge to guide IT-related decision making, but further growth of this body of knowledge is required as the health IT domain and technologies are continuously evolving, leading to new functionalities and applications. However, EBHI should not wait until retrospective evidence is available - increasingly policy makers should draw on available prior and external evidence to influence design and development processes so as to ensure that health IT is devised in response to a delivery process need and not as an IT driven goal. EBHI should thereby seek to move forward significantly the metric that only some 20% of IT investment is truly successful. PMID- 27198118 TI - Appendix: Resources on Health IT Evaluation. PMID- 27198121 TI - Extraction, composition, and functional properties of dried alfalfa (Medicago sativa L.) leaf protein. AB - BACKGROUND: Alfalfa is considered a potential feedstock for biofuels; co-products with value-added uses would enhance process viability. This work evaluated dried alfalfa leaves for protein production and describes the functional properties of the protein. RESULTS: Dried alfalfa leaves contained 260 g kg-1 dry basis (DB) crude protein, with albumins being the major fraction (260 g kg-1 of total protein). Alkali solubilization for 2 h at 50 degrees C, acid precipitation, dialysis, and freeze-drying produced a protein concentrate (600 g kg-1 DB crude protein). Alfalfa leaf protein concentrate showed moderate solubility (maximum 500 g kg-1 soluble protein from pH 5.5 to 10), excellent emulsifying properties (activity 158-219 m2 g-1 protein, stability 17-49 min) and minimal loss of solubility during heating at pH >= 7.0. CONCLUSIONS: It is technically feasible to extract protein with desirable emulsifying and heat stability properties from dried alfalfa leaves; however, the dried form may not be a practical starting material for protein production, given the difficulty of achieving high yields and high-purity protein product. (c) 2016 Society of Chemical Industry. PMID- 27198122 TI - Midazolam for sedation before procedures. AB - BACKGROUND: Midazolam is used for sedation before diagnostic and therapeutic medical procedures. It is an imidazole benzodiazepine that has depressant effects on the central nervous system (CNS) with rapid onset of action and few adverse effects. The drug can be administered by several routes including oral, intravenous, intranasal and intramuscular. OBJECTIVES: To determine the evidence on the effectiveness of midazolam for sedation when administered before a procedure (diagnostic or therapeutic). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL to January 2016), MEDLINE in Ovid (1966 to January 2016) and Ovid EMBASE (1980 to January 2016). We imposed no language restrictions. SELECTION CRITERIA: Randomized controlled trials in which midazolam, administered to participants of any age, by any route, at any dose or any time before any procedure (apart from dental procedures), was compared with placebo or other medications including sedatives and analgesics. DATA COLLECTION AND ANALYSIS: Two authors extracted data and assessed risk of bias for each included study. We performed a separate analysis for each different drug comparison. MAIN RESULTS: We included 30 trials (2319 participants) of midazolam for gastrointestinal endoscopy (16 trials), bronchoscopy (3), diagnostic imaging (5), cardioversion (1), minor plastic surgery (1), lumbar puncture (1), suturing (2) and Kirschner wire removal (1). Comparisons were: intravenous diazepam (14), placebo (5) etomidate (1) fentanyl (1), flunitrazepam (1) and propofol (1); oral chloral hydrate (4), diazepam (2), diazepam and clonidine (1); ketamine (1) and placebo (3); and intranasal placebo (2). There was a high risk of bias due to inadequate reporting about randomization (75% of trials). Effect estimates were imprecise due to small sample sizes. None of the trials reported on allergic or anaphylactoid reactions. Intravenous midazolam versus diazepam (14 trials; 1069 participants)There was no difference in anxiety (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.39 to 1.62; 175 participants; 2 trials) or discomfort/pain (RR 0.60, 95% CI 0.24 to 1.49; 415 participants; 5 trials; I2 = 67%). Midazolam produced greater anterograde amnesia (RR 0.45; 95% CI 0.30 to 0.66; 587 participants; 9 trials; low-quality evidence). Intravenous midazolam versus placebo (5 trials; 493 participants)One trial reported that fewer participants who received midazolam were anxious (3/47 versus 15/35; low-quality evidence). There was no difference in discomfort/pain identified in a further trial (3/85 in midazolam group; 4/82 in placebo group; P = 0.876; very low quality evidence). Oral midazolam versus chloral hydrate (4 trials; 268 participants)Midazolam increased the risk of incomplete procedures (RR 4.01; 95% CI 1.92 to 8.40; moderate-quality evidence). Oral midazolam versus placebo (3 trials; 176 participants)Midazolam reduced pain (midazolam mean 2.56 (standard deviation (SD) 0.49); placebo mean 4.62 (SD 1.49); P < 0.005) and anxiety (midazolam mean 1.52 (SD 0.3); placebo mean 3.97 (SD 0.44); P < 0.0001) in one trial with 99 participants. Two other trials did not find a difference in numerical rating of anxiety (mean 1.7 (SD 2.4) for 20 participants randomized to midazolam; mean 2.6 (SD 2.9) for 22 participants randomized to placebo; P = 0.216; mean Spielberger's Trait Anxiety Inventory score 47.56 (SD 11.68) in the midazolam group; mean 52.78 (SD 9.61) in placebo group; P > 0.05). Intranasal midazolam versus placebo (2 trials; 149 participants)Midazolam induced sedation (midazolam mean 3.15 (SD 0.36); placebo mean 2.56 (SD 0.64); P < 0.001) and reduced the numerical rating of anxiety in one trial with 54 participants (midazolam mean 17.3 (SD 18.58); placebo mean 49.3 (SD 29.46); P < 0.001). There was no difference in meta-analysis of results from both trials for risk of incomplete procedures (RR 0.14, 95% CI 0.02 to 1.12; downgraded to low-quality evidence). AUTHORS' CONCLUSIONS: We found no high-quality evidence to determine if midazolam, when administered as the sole sedative agent prior to a procedure, produces more or less effective sedation than placebo or other medications. There is low-quality evidence that intravenous midazolam reduced anxiety when compared with placebo. There is inconsistent evidence that oral midazolam decreased anxiety during procedures compared with placebo. Intranasal midazolam did not reduce the risk of incomplete procedures, although anxiolysis and sedation were observed. There is moderate-quality evidence suggesting that oral midazolam produces less effective sedation than chloral hydrate for completion of procedures for children undergoing non-invasive diagnostic procedures. PMID- 27198123 TI - Programming social behavior by the maternal fragile X protein. AB - The developing fetus and neonate are highly sensitive to maternal environment. Besides the well-documented effects of maternal stress, nutrition and infections, maternal mutations, by altering the fetal, perinatal and/or early postnatal environment, can impact the behavior of genetically normal offspring. Mutation/premutation in the X-linked FMR1 (encoding the translational regulator FMRP) in females, although primarily responsible for causing fragile X syndrome (FXS) in their children, may also elicit such maternal effects. We showed that a deficit in maternal FMRP in mice results in hyperactivity in the genetically normal offspring. To test if maternal FMRP has a broader intergenerational effect, we measured social behavior, a core dimension of neurodevelopmental disorders, in offspring of FMRP-deficient dams. We found that male offspring of Fmr1(+/-) mothers, independent of their own Fmr1 genotype, exhibit increased approach and reduced avoidance toward conspecific strangers, reminiscent of 'indiscriminate friendliness' or the lack of stranger anxiety, diagnosed in neglected children and in patients with Asperger's and Williams syndrome. Furthermore, social interaction failed to activate mesolimbic/amygdala regions, encoding social aversion, in these mice, providing a neurobiological basis for the behavioral abnormality. This work identifies a novel role for FMRP that extends its function beyond the well-established genetic function into intergenerational non-genetic inheritance/programming of social behavior and the corresponding neuronal circuit. As FXS premutation and some psychiatric conditions that can be associated with reduced FMRP expression are more prevalent in mothers than full FMR1 mutation, our findings potentially broaden the significance of FMRP-dependent programming of social behavior beyond the FXS population. PMID- 27198124 TI - ICSI outcomes in men undergoing TESE for azoospermia and impact of maternal age. AB - This retrospective study compared clinical outcomes in men with obstructive and nonobstructive azoospermia after ICSI following testicular sperm extraction and the influence of maternal age. Fertilisation rates, embryo quality, pregnancy rates, miscarriage rates and live birth rates were evaluated. Men with obstructive azoospermia (OA) had significantly higher rates of diploid fertilisation and clinical pregnancy than men with nonobstructive azoospermia (NOA), but miscarriage rates and live birth rates were not significantly different. The higher rates of fertilisation, embryo quality and clinical pregnancy in men with OA were statistically significant when their female partners were <35 years but results were similar in both groups when female partners >=35 years. Although the OA group had better overall quality embryos than the NOA group when maternal age was <35 years, embryologists can select the morphologically better embryos for transfer, eliminating the effect of embryo quality differences present in these two groups. Understanding more about factors that affect TESE/ICSI outcomes will not only help us predict patients' outcomes but it can help us educate and better counsel our patients. PMID- 27198125 TI - Cuticle-degrading proteases and toxins as virulence markers of Beauveria bassiana (Balsamo) Vuillemin. AB - Beauveria bassiana is one of the most known entomopathogenic fungal species and its entomopathogenic mechanism involves several bioactive metabolites, mainly cuticle-degrading enzymes and toxic molecules, which are predicted to play a key role as virulence factors. In this study six Beauveria bassiana strains (B 13/I03, B 13/I11, B 13/I49, B 13/I57, B 13/I63, and B 13/I64) were assayed against Tenebrio molitor larvae. Enzymatic activity of total proteases and specifically Pr 1 and Pr 2, as well as the production of toxic compounds were investigated in each fungal strain. Toxins were detected both in vitro-in medium filtrates and mycelia-and in vivo-in Tenebrio molitor larvae infected by the fungal strains tested. B 13/I11 and B 13/I63 strains showed the most significant entomopathogenic activity against Tenebrio molitor larvae (cumulative mortality rate 100 and 97%, respectively; average survival time 5.85 and 6.74 days, respectively). A widely variable and fungal strain-dependent enzymatic activity of total proteases, Pr 1 and Pr 2 was found. Beauvericin, beauvericin A and bassianolide resulted the most prevalent toxins detected in the substrates analyzed. It has been found that an increase of beauvericin content in vivo resulted significantly correlated to a decrease of Tenebrio molitor larvae average survival time in entomopathogenic bioassay (inverse correlation). The involvement of beauvericin in B. bassiana entomopathogenic process is confirmed; in vitro analysis of cuticle degrading proteases activity and toxins production in relation to the methods adopted resulted insufficient for a rapid screening to determine the virulence of B. bassiana strains against Tenebrio molitor larvae. PMID- 27198126 TI - Ultrasound-accelerated Thrombolysis in a Sub-massive Pulmonary Embolism. PMID- 27198127 TI - The Importance of Family-genetic Screening: The Phenotype Caused by the p.L3778F Ryanodine Receptor Mutation is Likely Less Severe Than Previously Thought. PMID- 27198128 TI - Bivalirudin Versus Unfractionated Heparin in Acute Coronary Syndromes: An Updated Meta-analysis of Randomized Trials. AB - INTRODUCTION AND OBJECTIVES: Contrasting data have been reported on bivalirudin as an anticoagulation strategy during percutaneous coronary interventions, offering theoretical benefits on bleeding complications but raising concerns on a potential increase in the risk of stent thrombosis. We performed an updated meta analysis to evaluate the efficacy and safety of bivalirudin compared with unfractionated heparin in patients undergoing percutaneous interventions for acute coronary syndromes. METHODS: Literature archives and main scientific sessions were scanned. The primary efficacy endpoint was 30-day overall mortality. Secondary endpoints were stent thrombosis and major bleeding. A prespecified analysis was conducted according to clinical presentation. RESULTS: Twelve randomized trials were included, involving 32 746 patients (52.5% randomized to bivalirudin). Death occurred in 1.8% of the patients, with no differences between bivalirudin and heparin (odds ratio = 0.91; 95% confidence interval, 0.77-1.08; P = .28; P for heterogeneity = .41). Similar results were obtained for patients with non-ST-segment elevation and in ST-segment elevation myocardial infarction. A significantly higher rate of stent thrombosis was observed with bivalirudin (odds ratio = 1.42; 95% confidence interval, 1.09-1.83; P = .008; P for heterogeneity = .09). Bivalirudin was associated with a significant reduction in the rate of major bleeding (odds ratio = 0.60; 95% confidence interval, 0.54-0.75; P < .00001; P for heterogeneity < .0001), which, however, was related to the differential use of glycoprotein IIb/IIIa inhibitors (r = -0.02 [-0.033 to -0.0032]; P = .02) and did not translate into survival benefits. CONCLUSIONS: In patients undergoing percutaneous coronary interventions, bivalirudin is not associated with a reduction in mortality compared with heparin but does increase stent thrombosis. The reduction in bleeding complications observed with bivalirudin does not translate into survival benefits but is rather influenced by a differential use of glycoprotein IIb/IIIa inhibitors. PMID- 27198130 TI - Inappropriate Shocks in a Patient with Subcutaneous ICD and Transvenous Pacemaker: Is it as it Seems? PMID- 27198129 TI - Red blood cell transfusion triggers in acute leukemia: a randomized pilot study. AB - BACKGROUND: Red blood cell (RBC) transfusion thresholds have yet to be examined in large randomized trials in hematologic malignancies. This pilot study in acute leukemia uses a restrictive compared to a liberal transfusion strategy. STUDY DESIGN AND METHODS: A randomized (2:1) study was conducted of restrictive (LOW) hemoglobin (Hb) trigger (7 g/dL) compared to higher (HIGH) Hb trigger (8 g/dL). The primary outcome was feasibility of conducting a larger trial. The four requirements for success required that more than 50% of the eligible patients could be consented, more than 75% of the patients randomized to the LOW arm tolerated the transfusion trigger, fewer than 15% of patients crossed over from the LOW arm to the HIGH arm, and no indication for the need to pause the study for safety concerns. Secondary outcomes included fatigue, bleeding, and RBCs and platelets transfused. RESULTS: Ninety patients were consented and randomly assigned to LOW to HIGH. The four criteria for the primary objective of feasibility were met. When the number of units transfused was compared, adjusting for baseline Hb, the LOW arm was transfused on average 8.0 (95% confidence interval [CI], 6.9-9.1) units/patient while the HIGH arm received 11.7 (95% CI, 10.1-13.2) units (p = 0.0003). There was no significant difference in bleeding events or neutropenic fevers between study arms. CONCLUSION: This study establishes feasibility for trial of Hb thresholds in leukemia through demonstration of success in all primary outcome metrics and a favorable safety profile. This population requires further study to evaluate the equivalence of liberal and restrictive transfusion thresholds in this unique clinical setting. PMID- 27198131 TI - Recombinant antibodies for diagnostics and therapy against pathogens and toxins generated by phage display. AB - Antibodies are valuable molecules for the diagnostic and treatment of diseases caused by pathogens and toxins. Traditionally, these antibodies are generated by hybridoma technology. An alternative to hybridoma technology is the use of antibody phage display to generate recombinant antibodies. This in vitro technology circumvents the limitations of the immune system and allows-in theory the generation of antibodies against all conceivable molecules. Phage display technology enables obtaining human antibodies from naive antibody gene libraries when either patients are not available or immunization is not ethically feasible. On the other hand, if patients or immunized/infected animals are available, it is common to construct immune phage display libraries to select in vivo affinity matured antibodies. Because the phage packaged DNA sequence encoding the antibodies is directly available, the antibodies can be smoothly engineered according to the requirements of the final application. In this review, an overview of phage display derived recombinant antibodies against bacterial, viral, and eukaryotic pathogens as well as toxins for diagnostics and therapy is given. PMID- 27198132 TI - Topical Ketoprofen Versus Placebo in Treatment of Acute Ankle Sprain in the Emergency Department. AB - BACKGROUND: Topical agents have been shown to be effective in soft tissue injuries and commonly used in outpatient clinics. However, the data regarding topical agents in the emergency department is insufficient, and they are not used often in the emergency department setting. The present study aimed to compare the effect of 2.5% topical ketoprofen (gel form) to placebo in patients presenting with ankle sprain to the emergency department. METHODS: Patients presenting with ankle sprain composed the study population. Study patients were randomized into 2 study arms: 2.5% ketoprofen gel and placebo administered over a 5-cm area locally. Pain alleviation was measured by visual analog scale at 15 and 30 minutes. A total of 100 patients were included in the final analysis. RESULTS: The median pain reduction in ketoprofen and placebo groups at 15 minutes was 27 (19.8-33.4) and 9 (7.6-17), respectively. The median pain reduction at 30 minutes for both groups was 42 (36-50.8) and 20 (17.6-24.4), respectively. Pain improvement either at 15 minutes (median difference: 16 [9-22]) or 30 minutes (median difference: 21 [15-27]) was better in the ketoprofen group than placebo. There were no adverse effects in either group. CONCLUSION: Ketoprofen gel was superior to placebo at 30 minutes in alleviating pain secondary to ankle sprain in the ED with a high safety profile. Further studies are needed concerning the effect of ketoprofen gel for long-term effects. LEVEL OF EVIDENCE: Level I, high quality prospective randomized study. PMID- 27198133 TI - A Computer-Aided Type-II Fuzzy Image Processing for Diagnosis of Meniscus Tear. AB - Meniscal tear is one of the prevalent knee disorders among young athletes and the aging population, and requires correct diagnosis and surgical intervention, if necessary. Not only the errors followed by human intervention but also the obstacles of manual meniscal tear detection highlight the need for automatic detection techniques. This paper presents a type-2 fuzzy expert system for meniscal tear diagnosis using PD magnetic resonance images (MRI). The scheme of the proposed type-2 fuzzy image processing model is composed of three distinct modules: Pre-processing, Segmentation, and Classification. lambda-nhancement algorithm is used to perform the pre-processing step. For the segmentation step, first, Interval Type-2 Fuzzy C-Means (IT2FCM) is applied to the images, outputs of which are then employed by Interval Type-2 Possibilistic C-Means (IT2PCM) to perform post-processes. Second stage concludes with re-estimation of "eta" value to enhance IT2PCM. Finally, a Perceptron neural network with two hidden layers is used for Classification stage. The results of the proposed type-2 expert system have been compared with a well-known segmentation algorithm, approving the superiority of the proposed system in meniscal tear recognition. PMID- 27198134 TI - Ambulatory assessment of walking balance after stroke using instrumented shoes. AB - BACKGROUND: For optimal guidance of walking rehabilitation therapy of stroke patients in an in-home setting, a small and easy to use wearable system is needed. In this paper we present a new shoe-integrated system that quantifies walking balance during activities of daily living and is not restricted to a lab environment. Quantitative parameters were related to clinically assessed level of balance in order to assess the additional information they provide. METHODS: Data of 13 participants who suffered a stroke were recorded while walking 10 meter trials and wearing special instrumented shoes. The data from 3D force and torque sensors, 3D inertial sensors and ultrasound transducers were fused to estimate 3D (relative) position, velocity, orientation and ground reaction force of each foot. From these estimates, center of mass and base of support were derived together with a dynamic stability margin, which is the (velocity) extrapolated center of mass with respect to the front-line of the base of support in walking direction. Additionally, for each participant step lengths and stance times for both sides as well as asymmetries of these parameters were derived. RESULTS: Using the proposed shoe-integrated system, a complete reconstruction of the kinematics and kinetics of both feet during walking can be made. Dynamic stability margin and step length symmetry were not significantly correlated with Berg Balance Scale (BBS) score, but participants with a BBS score below 45 showed a small-positive dynamic stability margin and more asymmetrical step lengths. More affected participants, having a lower BBS score, have a lower walking speed, make smaller steps, longer stance times and have more asymmetrical stance times. CONCLUSIONS: The proposed shoe-integrated system and data analysis methods can be used to quantify daily-life walking performance and walking balance, in an ambulatory setting without the use of a lab restricted system. The presented system provides additional insight about the balance mechanism, via parameters describing walking patterns of an individual subject. This information can be used for patient specific and objective evaluation of walking balance and a better guidance of therapies during the rehabilitation. TRIAL REGISTRATION: The study protocol is a subset of a larger protocol and registered in the Netherlands Trial Registry, number NTR3636 . PMID- 27198135 TI - Genome wide association mapping for grain shape traits in indica rice. AB - MAIN CONCLUSION: Using genome-wide association mapping, 47 SNPs within 27 significant loci were identified for four grain shape traits, and 424 candidate genes were predicted from public database. Grain shape is a key determinant of grain yield and quality in rice (Oryza sativa L.). However, our knowledge of genes controlling rice grain shape remains limited. Genome-wide association mapping based on linkage disequilibrium (LD) has recently emerged as an effective approach for identifying genes or quantitative trait loci (QTL) underlying complex traits in plants. In this study, association mapping based on 5291 single nucleotide polymorphisms (SNPs) was conducted to identify significant loci associated with grain shape traits in a global collection of 469 diverse rice accessions. A total of 47 SNPs were located in 27 significant loci for four grain traits, and explained ~44.93-65.90 % of the phenotypic variation for each trait. In total, 424 candidate genes within a 200 kb extension region (+/-100 kb of each locus) of these loci were predicted. Of them, the cloned genes GS3 and qSW5 showed very strong effects on grain length and grain width in our study. Comparing with previously reported QTLs for grain shape traits, we found 11 novel loci, including 3, 3, 2 and 3 loci for grain length, grain width, grain length width ratio and thousand grain weight, respectively. Validation of these new loci would be performed in the future studies. These results revealed that besides GS3 and qSW5, multiple novel loci and mechanisms were involved in determining rice grain shape. These findings provided valuable information for understanding of the genetic control of grain shape and molecular marker assistant selection (MAS) breeding in rice. PMID- 27198136 TI - Effect of non-invasive remote ischemic preconditioning on intra-renal perfusion in volunteers. AB - Remote ischemic preconditioning may attenuate renal injury and protect the kidney during subsequent inflammatory or ischemic stress. However, the mechanism of such a protection is not well understood. The aim of this study was to investigate the impact of remote ischemic preconditioning on renal resistivity index (RRI) in nine healthy volunteers. In six volunteers, four cycles of 4-min inflation of a blood pressure cuff were applied to one upper arm, followed by 4-min reperfusion with the cuff deflated. RRI was determined using Doppler echography during each cuff deflated period. Measures were also performed in three volunteers without preconditioning. The median value of RRI significantly decreased progressively from 0.59 [0.53-0.62] before the remote conditioning (baseline) to 0.49 [0.46 0.53] at the end of the experiment (p < 0.001) whereas there was no change in controls. In this study, for the first time, we have clearly shown in a small group of subjects that remote ischemic preconditioning can induce a significantly decrease in RRI through increased intra-renal perfusion. PMID- 27198138 TI - Protective effects of estrogen and bortezomib in kidney tissue of post-menopausal rats: an ultrastructural study. AB - PURPOSE: Symptoms and disorders related to menopause and its associated estrogen deficiency have become a considerable health concern worldwide. Ovarian hormone depletion/estrogen deficiency can be usefully studied using animal models after removal of the ovaries [ovariectomy (Ovx)]. This study assessed renal changes after Ovx-induced estrogen deficiency in a rat model. METHODS: Rats were randomly allotted into one control group (group I, healthy) and three study groups (group II, Ovx group; group III, Ovx +17beta-estradiol group; and group IV, Ovx + bortezomib group). RESULTS: In the Ovx group (group II), thickening of glomerular capillary walls, narrowing of Bowman's capsular space, glomerular hypertrophy, atrophic tubules, and loss of the basal membranes of the tubules were observed. Mesangial cell proliferation was observed, particularly in the glomerulus. Immunohistochemical (IHC) staining studies in this group showed dense staining in the mesangial cells, tubular cell Nf-KB/p65, and caspase-3. Groups III and IV (Ovx +17beta-estradiol and Ovx + bortezomib) showed decreased NF-kB/p65 and caspase-3 expression compared with the Ovx group (p < 0.05). CONCLUSION: In renal failure related to estrogen deficiency caused by Ovx, 17beta-estradiol and bortezomib have a protective effect on renal tissue. PMID- 27198137 TI - Renal involvement in primary antiphospholipid syndrome. AB - Antiphospholipid syndrome is an autoimmune disorder characterized by recurrent venous or arterial thrombosis and/or pregnancy-related problems associated with persistently elevated levels of antiphospholipid antibodies. The kidney is a major target organ in both primary and secondary antiphospholipid syndrome. This review describes several aspects of the renal involvement in the primary form of the syndrome, in particular the histological pattern of the so-called antiphospholipid syndrome nephropathy (APSN). APSN is a vascular nephropathy characterized by small vessel vaso-occlusive lesions associated with fibrous intimal hyperplasia of interlobular arteries, recanalizing thrombi in arteries and arterioles, and focal atrophy, a constellation of morphological lesions suggestive of primary antiphospholipid syndrome. PMID- 27198139 TI - Surgical management of osteonecrosis of the humeral head: a systematic review. AB - PURPOSE: Osteonecrosis of the humeral head is a rare diagnosis. The aim of this systematic review was to identify published studies and analyse the best clinical evidence available related to the surgical management of osteonecrosis of the humeral head. METHODS: A systematic electronic search was performed using the PubMed (MEDLINE), EMBASE and Cochrane Library databases. Published studies that reported the outcomes for adult patients treated surgically for osteonecrosis of the humeral head were included. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement was followed. RESULTS: Twelve studies were included: five prospective case series and seven retrospective case series. A total of 309 patients, comprising 382 shoulders, were included. Three main surgical procedures were evaluated: core decompression, hemi-arthroplasty and total shoulder arthroplasty. CONCLUSIONS: Based on the current available data, core decompression is a safe and effective option for treating low-grade osteonecrosis of the humeral head, while hemi-arthroplasty and total shoulder arthroplasty should be considered for high-grade osteonecrosis. More studies and better-designed trials are needed in order to enrich the evidence and enable researchers to draw stronger conclusions. Since osteonecrosis is an uncommon, though challenging disease, a proper knowledge of its treatment is needed. LEVEL OF EVIDENCE: IV. PMID- 27198141 TI - International Conference Symposia. PMID- 27198142 TI - Plant Contributed Papers. PMID- 27198143 TI - Education Posters. PMID- 27198140 TI - No negative effect on patient-reported outcome of concomitant cartilage lesions 5 9 years after ACL reconstruction. AB - PURPOSE: To compare patient-reported outcome 5-9 years after anterior cruciate ligament (ACL) reconstruction in patients with and without a concomitant full thickness [International Cartilage Repair Society (ICRS) grade 3-4] cartilage lesion. METHODS: This is a prospective follow-up of a cohort of 89 patients that were identified in the Norwegian National Knee Ligament Registry and included in the current study in 2007, consisting of 30 primary ACL-reconstructed patients with a concomitant, isolated full-thickness cartilage lesion (ICRS grade 3 and 4) and 59 matched controls without cartilage lesions (ICRS grade 1-4). At a median follow-up of 6.3 years (range 4.9-9.1) after ACL reconstruction, 74 (84 %) patients completed the Knee Injury and Osteoarthritis Outcome Score (KOOS), which was used as the main outcome measure. Secondary outcomes included radiographic evaluation according to the Kellgren-Lawrence criteria of knee osteoarthritis (OA). RESULTS: At follow-up, 5-9 years after ACL reconstruction, no statistically significant differences in KOOS were detected between patients with a concomitant full-thickness cartilage lesion and patients without concomitant cartilage lesions. Radiographic knee OA of the affected knee, defined as Kellgren and Lawrence >=2, was significantly more frequent in subjects without a concomitant cartilage lesion (p = 0.016). CONCLUSION: ACL reconstruction performed in patients with an isolated concomitant full-thickness cartilage lesion restored patient-reported knee function to the same level as ACL reconstruction performed in patients without concomitant cartilage lesions, 5-9 years after surgery. This should be considered in the preoperative information given to patients with such combined injuries, in terms of the expected outcome after ACL reconstruction and in the counselling and decision-making on the subject of surgical treatment of the concomitant cartilage lesion. LEVEL OF EVIDENCE: Prognostic; prospective cohort study, Level I. PMID- 27198146 TI - Keynote Symposium. PMID- 27198145 TI - Animal Posters. PMID- 27198144 TI - Plant Posters. PMID- 27198149 TI - Animal Symposia and Workshops. PMID- 27198147 TI - Plenary Symposia. PMID- 27198150 TI - Plant Symposia and Workshops. PMID- 27198151 TI - Animal and Education Contributed Papers. PMID- 27198152 TI - Combination Therapy of Nifedipine and Sulphonylureas Exhibits a Mutual Antagonistic Effect on the Endothelial Cell Dysfunction Induced by Hyperglycemia Linked to Vascular Disease. AB - BACKGROUND/AIMS: By inducing severe endothelial impairment, hypertension and diabetes are two leading causes of morbidity and mortality. Hypertensive patients with concomitant diabetes must take both antihypertensive and hypoglycaemic medications, for which there is a lack of experimental and clinical guidelines. This study aimed to examine the interaction between these two types of medication on the endothelial cell function. METHODS: The effect of antihypertensive (nifedipine and irbesartan) and anti-diabetic (metformin and glibenclamide/glimepiride) drugs on human umbilical vein cells (HUVECs) function was examined using a modified Boyden chamber assay. The intracellular NO and O2- levels of HUVECs were detected through flow cytometry. RESULTS: Our findings showed that nifedipine/sulphonylurea monotherapy significantly attenuated high glucose-induced (33 mM) HUVECs migration incapacity, while combination therapy of nifedipine and glibenclamide/glimepiride showed no protective effect. Both nifedipine/metformin monotherapy and combined therapy significantly mitigated the migration incapacity induced by high glucose in HUVECs. Combined with either metformin or sulphonylureas, irbesartan therapy was able to attenuate the high glucose-induced migration incapacity of HUVECs. Nifedipine monotherapy decreased the O2- levels and increased the NO levels in in vitro-cultured HUVECs treated with high glucose. However, the combination therapy of nifedipine and glibenclamide increased the O2- levels and decreased the NO levels compared to the nifedipine monotherapeutic group. CONCLUSION: The nifedipine and glibenclamide/glimepiride combination exerted a mutual antagonistic effect on the protection from high glucose-induced impairment in endothelial cells, which might be partially attributed to the increased O2- level and decreased NO level. These results imply that calcium channel blockers + sulphonylurea combination therapy warrants further attention in patients suffering from both hypertension and diabetes. PMID- 27198153 TI - Rights-Based Approaches to Ensure Sustainable Nutrition Security. AB - In India, a rights-based approach has been used to address large-scale malnutrition, including both micro- and macro-level nutrition deficiencies. Stunting, which is an intergenerational chronic consequence of malnutrition, is especially widespread in India (38% among children under 5 years old). To tackle this problem, the government of India has designed interventions for the first 1,000 days, a critical period of the life cycle, through a number of community based programs to fulfill the rights to food and life. However, the entitlements providing these rights have not yet produced the necessary changes in the malnutrition status of people, especially women and children. The government of India has already implemented laws and drafted a constitution that covers the needs of its citizens, but corruption, bureaucracy, lack of awareness of rights and entitlements and social discrimination limit people's access to basic rights and services. To address this crisis, Welthungerhilfe India, working in remote villages of the most backward states in India, has shifted from a welfare-based approach to a rights-based approach. The Fight Hunger First Initiative, started by Welthungerhilfe in 2011, is designed on the premise that in the long term, poor people can only leave poverty behind if adequate welfare systems are in place and if basic rights are fulfilled; these rights include access to proper education, sufficient access to adequate food and income, suitable health services and equal rights. Only then can the next generation of disadvantaged populations look forward to a new and better future and can growth benefit the entire society. The project, co-funded by the Federal Ministry for Economic Cooperation and Development, is a long-term multi-sectoral program that involves institution-building and empowerment. PMID- 27198155 TI - Effect of Angiotensin-Converting Enzyme Inhibitors in Contrast-Induced Nephropathy: A Meta-Analysis. AB - AIMS: The purpose of this study was to evaluate the effect of angiotensin converting enzyme inhibitors (ACEIs) on contrast-induced nephropathy (CIN) in patients undergoing coronary angiography or percutaneous coronary intervention (PCI). METHODS: We searched the Medline, Embase, Cochrane Library, China National Knowledge Infrastructure, Chongqing VIP database and Wanfang database up to December 2014. Pooled risk ratios (RRs) or weighted mean difference (WMD) with their 95% CIs for the CIN incidence, serum creatinine (SCr), estimated glomerular filtration rate (eGFR) and blood urea nitrogen (BUN) of the patients were collected and calculated using the software Review Manager 5.2. RESULTS: A total of 12 separate studies including 1,868 patients (1,011 ACEI cases and 857 controls) were considered in the meta-analysis. The overall RR of the incident CIN in the ACEI group vs. the control group was 0.95 (95% CI 0.57-1.58), and the total WMDs of the x0394;SCr, x0394;eGFR and x0394;BUN were -0.01 (95% CI -0.04 to 0.02), 5.71 (95% CI -0.66 to 12.09) and 0.78 (95% CI -0.16 to 1.73), respectively. Besides, the RR of CIN incidence in the captopril group vs. the control group was 0.72 (95% CI 0.25-2.05, p = 0.54), and the pooled WMD of the x0394;SCr was -0.13 (95% CI -0.21 to -0.06, p < 0.01). CONCLUSION: This meta analysis suggests that ACEIs administration has no significant influence in the CIN of patients undergoing coronary angiography or PCI; however, captopril might have the potential to prevent CIN. PMID- 27198154 TI - Regulation of miR-200c and miR-141 by Methylation in Prostate Cancer. AB - BACKGROUND: In prostate cancer (PCa), abnormal expression of several microRNAs (miRNAs) has been previously reported. Increasing evidence shows that aberrant epigenetic regulation of miRNAs is a contributing factor to their altered expression in cancer. In this study, we investigate whether expression of miR 200c and miR-141 in PCa is related to the DNA methylation status of their promoter. METHODS: PCR analysis of miR-200c and miR-141, and CpG methylation analysis of their common promoter, was performed in PCa cell-lines and in archived prostate biopsy specimens. The biological significance of miR-200c and miR-141 expression in prostate cancer cells was assessed by a series of in vitro bioassays and the effect on proposed targets DNMT3A and TET1/TET3 was investigated. The effect on promoter methylation status in cells treated with demethylating agents was also examined. RESULTS: miR-200c and miR-141 are both highly elevated in LNCaP, 22RV1, and DU145 cells, but significantly reduced in PC3 cells. This correlates inversely with the methylation status of the miR 200c/miR-141 promoter, which is unmethylated in LNCaP, 22RV1, and DU145 cells, but hypermethylated in PC3. In PC3 cells, miR-200c and miR-141 expression is subsequently elevated by treatment with the demethylating drug decitabine (5-aza 2'deoxycytidine) and by knockdown of DNA methyltransferase 1 (DNMT1), suggesting their expression is regulated by methylation. Expression of miR-200c and miR-141 in prostate biopsy tissue was inversely correlated with methylation in promoter CpG sites closest to the miR-200c/miR-141 loci. In vitro, over-expression of miR 200c in PC3 cells inhibited growth and clonogenic potential, as well as inducing apoptosis. Expression of the genes DNMT3A and TET1/TET3 were down-regulated by miR-200c and miR-141 respectively. Finally, treatment with the soy isoflavone genistein caused demethylation of the promoter CpG sites closest to the miR 200c/miR-141 loci resulting in increased miR-200c expression. CONCLUSIONS: Our findings provide evidence that miR-200c and miR-141 are under epigenetic regulation in PCa cells. We propose that profiling their expression and methylation status may have potential as a novel biomarker or focus of therapeutic intervention in the diagnosis and prognosis of PCa. Prostate 76:1146 1159, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27198156 TI - Engaging African and Caribbean Immigrants in HIV Testing and Care in a Large US City: Lessons Learned from the African Diaspora Health Initiative. AB - The lifting in 2010 of the HIV entry ban eliminated an access point for HIV testing of the foreign-born. The African Diaspora Health Initiative (ADHI) was developed to examine alternative pathways to testing for African and Caribbean persons. The ADHI consists of Clinics Without Walls (CWW) held in community settings. HIV testing is offered to participants along with hypertension and diabetes screening. A survey is administered to participants. Descriptive data were analyzed using SAS 9.2. Between 2011 and 2015, 4152 African and Caribbean individuals participated in 352 CWW. Participants were mostly (67.7 %) African. HIV rates were lowest in Caribbean women (0.4 %) and highest in Caribbean men (8.4 %). Efforts to engage African and Caribbean communities in HIV testing are important given the elimination of the HIV entry ban and continued immigration to the US from areas of higher prevalence. The ADHI offers a successful model of engagement. PMID- 27198157 TI - Understanding Food Insecurity in the USA and Canada: Potential Insights for Europe. AB - Food insecurity is a leading nutrition-related health care issue in the USA due to the magnitude of the problem (almost 50 million Americans are food insecure) and its association with a wide array of negative health and other outcomes. Alongside this interest in the USA, there has also been growing interest in Canada. In contrast, food insecurity has received less attention in Europe. Nevertheless, there is both direct and indirect evidence that food insecurity and its attendant consequences are present in Europe. Given the similarities between the USA, Canada, and Europe, previous research can offer numerous insights into the causes and consequences of food insecurity in Europe and possible directions to address these through measurement and public policies. I first cover the methods used to measure food insecurity in the USA and Canada. In both countries, a series of 18 questions in the Core Food Security Module are used to identify whether a household is food insecure. I then briefly cover the current extent of food insecurity in each country along with some discussion of the recent history of food insecurity. A central advantage to using the Core Food Security Module in Europe is that the measure has been proven useful in other high-income countries, and using a standardized measure would allow for cross-country comparisons. I next cover two large-scale food assistance programs from the USA, the Supplemental Nutrition Assistance Program (formerly known as the Food Stamp Program) and the National School Lunch Program. For each, I summarize how the program is structured, how eligibility is established, and how participation proceeds. Europe has generally used income-based assistance programs to improve the well-being of low-income households; I consider a couple of reasons for why food assistance programs may also be worth considering. PMID- 27198158 TI - Junior doctors will have a month to look at details of new contract. PMID- 27198159 TI - Body surface area as a prognostic marker in chronic heart failure patients: results from the Heart Failure Registry of the Heart Failure Association of the European Society of Cardiology. AB - AIMS: The 'obesity paradox' is consistently observed in patients with heart failure (HF). We investigated the relationship of body surface area (BSA) to mortality and hospitalizations in patients with chronic HF. METHODS AND RESULTS: Data from the outpatient cohort of the observational, prospective, Heart Failure Long-Term Registry of the Heart Failure Association of the European Society of Cardiology was analysed in order to evaluate the prognostic significance of BSA in chronic HF. A total of 9104 chronic HF patients (age 64.8 +/- 13.4 years; 71.6% males) were enrolled. Mortality during 1-year follow-up was observed in 718 of 8875 (8.1%) patients. A progressive, inverse relationship between all-cause mortality and BSA levels was observed; the adjusted hazard ratio (HR) for 1-year mortality was 1.823 [95% confidence interval (CI) 1.398-2.376], P < 0.001 for the lowest quartile of BSA <1.78 m(2) , and 1.255, 95% CI 1.000-1.576, P = 0.05 for the middle two quartiles (1.78 <=BSA <=2.07 m(2) ), compared with the highest quartile (BSA >2.07 m(2) ). For each increase of 0.1 m(2) in BSA, an adjusted HR of 0.908 (95% CI 0.870-0.948), P < 0.001 for mortality was calculated. HF hospitalizations were not associated with BSA subgroup distribution. In both genders, subjects within the lowest BSA quartile (males <1.84 m(2) and females <1.64 m(2) ) had significantly higher mortality rates during follow-up (log-rank P < 0.0001). However, the stepwise association with mortality was more distinct in males. CONCLUSIONS: Total and cardiovascular mortality, but not HF hospitalizations was inversely associated with BSA levels in chronic HF patients. BSA may serve as a prognostic indicator for adverse outcome in HF patients. PMID- 27198160 TI - Difference in Visual Social Predispositions Between Newborns at Low- and High risk for Autism. AB - Some key behavioural traits of Autism Spectrum Disorders (ASD) have been hypothesized to be due to impairments in the early activation of subcortical orienting mechanisms, which in typical development bias newborns to orient to relevant social visual stimuli. A challenge to testing this hypothesis is that autism is usually not diagnosed until a child is at least 3 years old. Here, we circumvented this difficulty by studying for the very first time, the predispositions to pay attention to social stimuli in newborns with a high familial risk of autism. Results showed that visual preferences to social stimuli strikingly differed between high-risk and low-risk newborns. Significant predictors for high-risk newborns were obtained and an accurate biomarker was identified. The results revealed early behavioural characteristics of newborns with familial risk for ASD, allowing for a prospective approach to the emergence of autism in early infancy. PMID- 27198162 TI - Use of antipsychotics and risk of myocardial infarction: a systematic review and meta-analysis. AB - AIM: There is emerging concern that antipsychotics may be associated with an increased risk of myocardial infarction (MI). A previous review identified five observational studies that did not provide an accurate estimate of the association between antipsychotic drug use and MI risk. More recent studies have produced variable results. METHODS: We performed a systematic review and meta analysis of observational studies to determine whether antipsychotic use affects the risk for MI. Our analysis included all observational studies that compared MI incidence among patients receiving antipsychotics vs. no treatment. RESULTS: Nine observational studies were included in the analysis. The odds for developing MI were 1.88-fold higher (odds ratio (OR) 1.88, 95% confidence interval (CI) 1.39, 2.54) in antipsychotic users compared with individuals who had not taken antipsychotics. Subgroup analyses found an OR of 2.48 (95% CI 1.66, 3.69) among patients with schizophrenia and an OR of 2.64 (95% CI 2.48, 2.81) among short term (<30 days) antipsychotic users. CONCLUSION: The findings of this meta analysis support an increased risk of MI in antipsychotic drug users. The present systematic review expands previous knowledge by demonstrating an increased and more pronounced risk in short term users. PMID- 27198163 TI - Objective Structured Assessment of Technical Skills for the Photoselective Vaporization of the Prostate Procedure: A Pilot Study. AB - INTRODUCTION AND OBJECTIVES: Photoselective vaporization of the prostate (PVP) is a frequently performed procedure by postgraduate trainees (PGTs). However, there is no PVP-specific objective assessment tool to evaluate the acquisition of PVP skills. The aim of the present study was to develop and validate an objective structured assessment of technical skills tool for the PVP procedure (PVP-OSATS). METHODS: This study was conducted in two phases. Phase I included the development of PVP-OSATS and assessment of its reliability and construct validity. Panel discussion among experts led to the development of the PVP-OSATS tool with 12 parameters, each scored from 1 (worst) to 5 (best) with a maximum score of 60. Laser prostatectomy experts and PGTs from postgraduate years (PGY) 4 and 5 were recruited. Inter-rater reliability, using Cohen's and Fleiss's kappa, was calculated for all parameters. To assess for construct validity, PGTs were compared with experts. Phase II included assessment of the concurrent validity of this novel tool. This was performed by recruiting Quebec urology PGTs between PGY 3 and -5 to test their PVP skills during the semiannual objective structured clinical examination using the validated GreenLight(TM) simulator. RESULTS: During phase I,116 intraoperative PVP-OSATS assessments were collected; 102 for PGTs and 14 for experts. Cohen's and Fleiss's kappa was adequate (k >= 0.6) for all 12 parameters, confirming adequate inter-rater reliability. There was significant difference between PGTs and experts in all PVP-OSATS parameters (p <= 0.01) except in respect to anatomical landmarks and instrument damage. During phase II, there was significant positive correlation between PVP-OSATS scores inside the operating room and global scores obtained by the GreenLight simulator (r = 0.814; p < 0.001). CONCLUSION: This study reports inter-rater reliability, construct, and concurrent validity of PVP-OSATS as a novel PVP-specific objective assessment tool. PMID- 27198161 TI - The long noncoding RNA CASC2 functions as a competing endogenous RNA by sponging miR-18a in colorectal cancer. AB - Recent evidence highlights the crucial regulatory roles of long noncoding RNAs (lncRNA) in tumor biology. In colorectal cancer (CRC), the expression of several lncRNAs is dysregulated and play essential roles in CRC tumorigenesis. However, the potential biological roles and regulatory mechanisms of the novel human lncRNA, CASC2 (cancer susceptibility candidate 2), in tumor biology are poorly understood. In this study, CASC2 expression was significantly decreased in CRC tissues and CRC cell lines, and decreased expression was significantly more frequent in patients with advanced tumor-node-metastasis stage disease (TNM III and IV) (P = 0.028). Further functional experiments indicate that CASC2 could directly upregulate PIAS3 expression by functioning as a competing endogenous RNA (ceRNA) for miR-18a. This interactions leads to the de-repression of genes downstream of STAT3 and consequentially inhibition of CRC cell proliferation and tumor growth in vitro and in vivo by extending the G0/G1-S phase transition. Taken together, these observations suggest CASC2 as a ceRNA plays an important role in CRC pathogenesis and may serve as a potential target for cancer diagnosis and treatment. PMID- 27198164 TI - Silicon Quantum Dot Nanoparticles with Antifouling Coatings for Immunostaining on Live Cancer Cells. AB - Fluorescent silicon quantum dots (SiQDs) have shown a great potential as antiphotobleaching, nontoxic and biodegradable labels for various in vitro and in vivo applications. However, fabricating SiQDs with high water-solubility and high photoluminescence quantum yield (PLQY) remains a challenge. Furthermore, for targeted imaging, their surface chemistry has to be capable of conjugating to antibodies, as well as sufficiently antifouling. Herein, antibody-conjugated SiQD nanoparticles (SiQD-NPs) with antifouling coatings composed of bovine serum albumin (BSA) and polyethylene glycol (PEG) are demonstrated for immunostaining on live cancer cells. The monodisperse SiQD-NPs of diameter about 130 nm are synthesized by a novel top-down method, including electrochemical etching, photochemical hydrosilylation, high energy ball milling, and "selective-etching" in HNO3 and HF. Subsequently, the BSA and PEG are covalently grafted on to the SiQD-NP surface through presynthesized chemical linkers, resulting in a stable, hydrophilic, and antifouling organic capping layer with isothiocyanates as the terminal functional groups for facile conjugation to the antibodies. The in vitro cell viability assay reveals that the BSA-coated SiQD-NPs had exceptional biocompatibility, with minimal cytotoxicity at concentration up to 1600 MUg mL( 1). Under 365 nm excitation, the SiQD-NP colloid emits bright reddish photoluminescence with PLQY = 45-55% in organic solvent and 5-10% in aqueous buffer. Finally, through confocal fluorescent imaging and flow cytometry analysis, the anti-HER2 conjugated SiQD-NPs show obvious specific binding to the HER2-overexpressing SKOV3 cells and negligible nonspecific binding to the HER2 nonexpressing CHO cells. Under similar experimental conditions, the immunofluorescence results obtained with the SiQD-NPs are comparable to those using conventional fluorescein isothiocyanate (FITC). PMID- 27198165 TI - Effectiveness of Inspiratory Termination Synchrony with Automatic Cycling During Noninvasive Pressure Support Ventilation. AB - BACKGROUND Pressure support ventilation (PSV) is a standard method for non invasive home ventilation. A bench study was designed to compare the effectiveness of patient-ventilator inspiratory termination synchronization with automated and conventional triggering in various respiratory mechanics models. MATERIAL AND METHODS Two ventilators, the Respironics V60 and Curative Flexo ST 30, connected to a Hans Rudolph Series 1101 lung simulator, were evaluated using settings that simulate lung mechanics in patients with chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), or normal lungs. Ventilators were operated with automated (Auto-Trak) or conventional high , moderate-, and low-sensitivity flow-cycling software algorithms, 5 cmH2O or 15 cmH2O pressure support, 5 cmH2O positive end-expiratory pressure (PEEP), and an air leak of 25-28 L/min. RESULTS Both ventilators adapted to the system leak without requiring adjustment of triggering settings. In all simulated lung conditions, automated cycling resulted in shorter triggering delay times (<100 ms) and lower triggering pressure-time product (PTPt) values. Tidal volumes (VT) increased with lower conventional cycling sensitivity level. In the COPD model, automated cycling had higher leak volumes and shorter cycling delay times than in conventional cycling. Asynchronous events were rare. Inspiratory time (Tinsp), peak expiratory flow (PEF), and cycling off delay time (Cdelay) increased as a result of reduction in conventional cycling sensitivity level. In the ARDS and normal adult lung models, premature cycling was frequent at the high-sensitive cycling level. CONCLUSIONS Overall, the Auto-Trak protocol showed better patient machine cycling synchronization than conventional triggering. This was evident by shorter triggering time delays and lower PTPt. PMID- 27198166 TI - Enhanced visible light photocatalytic activity of Gd-doped BiFeO3 nanoparticles and mechanism insight. AB - To investigate the effect of Gd doping on photocatalytic activity of BiFeO3 (BFO), Gd-doped BFO nanoparticles containing different Gd doping contents (Bi(1 x)GdxFeO3, x = 0.00, 0.01, 0.03, 0.05) were synthesized using a facile sol-gel route. The obtained products were characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectra, and ultraviolet-visible diffuse reflectance spectroscopy, and their photocatalytic activities were evaluated by photocatalytic decomposition of Rhodamine B in aqueous solution under visible light irradiation. It was found that the Gd doping content could significantly affect the photocatalytic activity of as-prepared Gd-doped BFO, and the photocatalytic activity increased with increasing the Gd doping content up to the optimal value and then decreased with further enhancing Gd doping content. To elucidate the enhanced photocatalytic mechanism of Gd-doped BFO, the trapping experiments, photoluminescence, photocurrent and electrochemical impedance measurements were performed. On the basis of these experimental results, the enhanced photocatalytic activities of Gd doped BFO could be ascribed to the increased optical absorption, the efficient separation and migration of photogenerated charge carriers as well as the decreased recombination probability of electron-hole pairs derived from the Gd doping effect. Meanwhile, the possible photocatalytic mechanism of Gd-doped BFO was critically discussed. PMID- 27198167 TI - Cellular and circuit mechanisms underlying spinocerebellar ataxias. AB - Degenerative ataxias are a common form of neurodegenerative disease that affect about 20 individuals per 100,000. The autosomal dominant spinocerebellar ataxias (SCAs) are caused by a variety of protein coding mutations (single nucleotide changes, deletions and expansions) in single genes. Affected genes encode plasma membrane and intracellular ion channels, membrane receptors, protein kinases, protein phosphatases and proteins of unknown function. Although SCA-linked genes are quite diverse they share two key features: first, they are highly, although not exclusively, expressed in cerebellar Purkinje neurons (PNs), and second, when mutated they lead ultimately to the degeneration of PNs. In this review we summarize ataxia-related changes in PN neurophysiology that have been observed in various mouse knockout lines and in transgenic models of human SCA. We also highlight emerging evidence that altered metabotropic glutamate receptor signalling and disrupted calcium homeostasis in PNs form a common, early pathophysiological mechanism in SCAs. Together these findings indicate that aberrant calcium signalling and profound changes in PN neurophysiology precede PN cell loss and are likely to lead to cerebellar circuit dysfunction that explains behavioural signs of ataxia characteristic of the disease. PMID- 27198168 TI - Association of low back and knee pain with falls in Japanese community-dwelling older adults: A 3-year prospective cohort study. AB - AIM: To examine whether the chronicity and intensity of low back pain (LBP) or knee pain (KP) was associated with the occurrence of falls among a community dwelling older population. METHODS: This was a community-based 3-year prospective cohort study. In 2009, baseline questionnaires were mailed to 3080 randomly selected residents aged 60-79 years; 2534 residents (82.3%) responded to the baseline survey, and 1- and 3-year follow-up surveys were subsequently mailed to them. The data for 1890 respondents who had no falls in the past year at baseline were analyzed. Associations between pain status (chronicity, intensity and persistence) and the occurrence of falls were analyzed by multivariable-adjusted logistic regression. RESULTS: A total of 197 (13.6%) participants had at least one fall during 12 months at 3-year follow up; of those, 68 (4.8%) had multiple falls, and 65 (4.5%) resulted in an injury. Chronicity and intensity of LBP were associated with injurious falls (P for trend = 0.033 and P for linearity = 0.041, respectively), and KP was associated with at least one fall (P for trend = 0.021 and P for linearity = 0.040, respectively). In addition, participants who had chronic pain persistently at both baseline and 1-year follow up had a higher risk of falls (LBP for injurious falls; adjusted odd ratio 2.46, 95% confidence interval 1.08-5.63, KP for at least one fall; adjusted odd ratio 2.39, 95% confidence interval 1.29-4.44), compared with those who had no pain at both time points. CONCLUSIONS: LBP and KP chronicity, intensity and persistence of chronic pain were associated with a greater risk of falls in older adults. Geriatr Gerontol Int 2017; 17: 875-884. PMID- 27198169 TI - Influence of increased patient age on longitudinal outcomes of root canal treatment: a systematic review. AB - OBJECTIVES: To conduct a systematic review of longitudinal endodontic outcomes in elders. BACKGROUND: Negative opinions about the prognosis of non-surgical root canal treatment (NSRCT) in elders affect decisions made by patients and dentists. Patient, caregiver and dentist attitudes and behaviours may interact to decrease the provision of NSRCT. Critical examination of the available evidence through systematic review could provide objective data to assist patients, caregivers, healthcare providers and third-party payers in making decisions about the efficacy of NSRCT in elders and provide a robust foundation for the health promotion of NSRCT in elders. METHODS: Inclusion/exclusion criteria were used for defined searches in MEDLINE and Cochrane CENTRAL. Title lists were scanned, and abstracts read to determine utility; articles meeting inclusion/exclusion criteria were analysed. Data were extracted and compiled into a table of evidence. RESULTS: Defined searching produced 3605 titles; 24 articles were included, nine prospective and 15 retrospective. Overall study quality was good. Patient samples mostly represented modern populations from countries with very high human development indices. Over 17 430 teeth were included. Meta-analysis was not attempted due to heterogeneity in reporting. All 24 included papers demonstrated that increased patient age did not decrease the success or survival rates of NSRCT. CONCLUSIONS: This systematic review of longitudinal NSRCT outcomes demonstrated that increased patient age did not decrease the success of NSRCT. Patient age is not a prognostic factor for NSRCT. Age should not be considered by dentists or patients when making NSRCT decisions. PMID- 27198171 TI - Association of breed and histopathological grade in canine mast cell tumours. AB - The aim of this study was to evaluate the relationship between breed and the histopathological grade of canine mast cell tumours (MCTs). A retrospective survey of pathology data of 9375 histopathologically confirmed diagnoses of cutaneous MCTs in the US was evaluated in the context of breed prevalence in over two million registered purebred dogs. Association of histopathological grade with breed, age, sex and spay/neuter status was assessed. The data indicate that the proportion of high-grade tumours increases with advancing age, and that male and intact dogs have increased odds of developing high-grade tumours. A significant difference in the proportion of high-grade tumours between breeds was detected. The Pug was at significantly increased risk of developing low/intermediate-grade tumours, but not high-grade tumours, resulting in preponderance of less aggressive MCTs in this breed. The results of this study suggest a genetic association for the development of high-grade MCTs. PMID- 27198170 TI - A phase 1 study of buparlisib and bevacizumab in patients with metastatic renal cell carcinoma progressing on vascular endothelial growth factor-targeted therapies. AB - BACKGROUND: The phosphatidylinositol-3 kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is dysregulated in patients with metastatic renal cell carcinoma (mRCC). Buparlisib is a pan-PI3K inhibitor with activity in advanced solid tumors. The primary objective of the current study was to determine the maximum tolerated dose (MTD) and dose-limiting toxicities of buparlisib and bevacizumab in patients with mRCC. Secondary objectives included efficacy, biomarker discovery, and additional toxicity. METHODS: This was a standard 3 + 3 dose escalation study of buparlisib (at a dose of 60-100 mg/day) and bevacizumab (at a dose of 10 mg/kg every 2 weeks). After the MTD was defined, 15 patients were accrued to the expansion cohort. RESULTS: Thirty-two patients were accrued (3 were treated at 60 mg/day, 21 were treated at 80 mg/day, 6 were treated at 100 mg/day, and 2 patients never received therapy). The majority of patients had clear cell histology (87%) and 50% had received >=2 prior lines of therapy. The MTD of buparlisib was 80 mg/day and that of bevacizumab was 10 mg/kg every 2 weeks. A total of 28 patients discontinued therapy: 17 because of disease progression, 7 because of toxicity, and 4 for other reasons. Dose-limiting toxicities included rash/pruritis, elevated lipase/amylase, anorexia, and psychiatric disorders (suicidal ideation, depression, and cognitive disturbances). Of the 30 patients who received at least 1 dose, 13% achieved a partial response (95% confidence interval, 4%-31%). Two patients harboring activating PI3KA mutations achieved 42% and 16% maximal tumor shrinkage, respectively. CONCLUSIONS: Buparlisib at a dose of 80 mg/day with bevacizumab was found to be a tolerable regimen with preliminary activity in vascular endothelial growth factor-refractory mRCC. The benefit of this combination may be of interest for future mRCC trials, possibly in a selected patient population. Cancer 2016;122:2389-2398. (c) 2016 American Cancer Society. PMID- 27198173 TI - Laparoscopic Removal of Streak Gonads in Turner Syndrome. AB - STUDY OBJECTIVE: To demonstrate the skills necessary for complete resection of bilateral streak gonads in Turner syndrome. DESIGN: Video case presentation with narration highlighting the key techniques used. The video was deemed exempt from formal review by our institutional review board. SETTING: Turner syndrome is a form of gonadal dysgenesis that affects 1 in 2500 live births. Patients often have streak gonads and may present with primary amenorrhea or premature ovarian failure. Patients with a mosaic karyotype that includes a Y chromosome are at increased risk for gonadoblastoma and subsequent transformation into malignancy. Gonadectomy is recommended for these patients, typically at adolescence. Streak gonads can be difficult to identify, and tissue margins are often in close proximity to critical retroperitoneal structures. Resection can be technically challenging and requires a thorough understanding of retroperitoneal anatomy and precise dissection techniques to ensure complete removal. INTERVENTIONS: Laparoscopic approach to bilateral salpingo-oophorectomy of streak gonads. Retroperitoneal dissection and ureterolysis are performed, with the aid of the Ethicon Harmonic Ace, to ensure complete gonadectomy. CONCLUSION: Careful and complete resection of gonadal tissue in the hands of a skilled laparoscopic surgeon is key for effective cancer risk reduction surgery in Turner syndrome mosaics. PMID- 27198172 TI - Novel function of Tau in regulating the effects of external stimuli on adult hippocampal neurogenesis. AB - Tau is a microtubule-associated neuronal protein found mainly in axons. However, its presence in dendrites and dendritic spines is particularly relevant due to its involvement in synaptic plasticity and neurodegeneration. Here, we show that Tau plays a novel in vivo role in the morphological and synaptic maturation of newborn hippocampal granule neurons under basal conditions. Furthermore, we reveal that Tau is involved in the selective cell death of immature granule neurons caused by acute stress. Also, Tau deficiency protects newborn neurons from the stress-induced dendritic atrophy and loss of postsynaptic densities (PSDs). Strikingly, we also demonstrate that Tau regulates the increase in newborn neuron survival triggered by environmental enrichment (EE). Moreover, newborn granule neurons from Tau(-/-) mice did not show any stimulatory effect of EE on dendritic development or on PSD generation. Thus, our data demonstrate that Tau(-/-) mice show impairments in the maturation of newborn granule neurons under basal conditions and that they are insensitive to the modulation of adult hippocampal neurogenesis exerted by both stimulatory and detrimental stimuli. PMID- 27198174 TI - Iron-mediated oxidative C-H coupling of arenes and alkenes directed by sulfur: an expedient route to dihydrobenzofurans. AB - A novel route to medicinally-relevant dihydrobenzofurans utilises a sulfur directed C-H ortho-coupling of arenes and unactivated terminal alkenes mediated by iron, and a palladium-catalysed deallylation/heterocyclisation sequence. The iron-mediated coupling affords linear products of alkene chloroarylation in good yield and with complete regioselectivity. The coupling likely proceeds by redox activation of the arene partner by iron(iii) and alkene addition to the resultant radical cation. PMID- 27198175 TI - Corrigendum: Indole-3-Acetic Acid Produced by Burkholderia heleia Acts as a Phenylacetic Acid Antagonist to Disrupt Tropolone Biosynthesis in Burkholderia plantarii. PMID- 27198176 TI - Enzymatic characterization of recombinant rat DDHD2: a soluble diacylglycerol lipase. AB - DDHD2 has been reported to exhibit phospholipase A1, triacylglycerol (TG) lipase and diacylglycerol (DG) lipase activities. However, the detailed enzymatic properties of DDHD2 have not yet been elucidated. In the current study, the substrate specificity of DDHD2 towards DG, TG and phosphatidic acid (PA) has been examined using highly purified recombinant rat DDHD2 (rDDHD2) with a liquid chromatography mass spectrometer. The k cat/Km value for DG (18:0/20:4) was much higher than those for TG (18:1/18:1/18:1), and PA (18:0/20:4) in the presence of sodium deoxycholate. The enzyme activity of rDDHD2 towards DG (18:0/20:4) was highest among all of the substrates tested. In addition, rDDHD2 was highly specific to DG substrates with a polyunsaturated fatty acid at their sn-2 position. The levels of 2-arachidonoylglycerol (2-AG) in CHO cells were quantified by gas chromatography-tandem mass spectrometry, showing that CHO cells expressing recombinant rDDHD2 contained higher levels of 2-AG when cells were treated with a monoacylglycerol lipase inhibitor, URB602. These results therefore support the idea that DDHD2 functions as a DG lipase in vivo and produces 2-AG. PMID- 27198177 TI - A risk stratification approach to assessing for true cases of measles in a highly vaccinated population. AB - OBJECTIVE: In Australia, the notification rate for measles fluctuates greatly between baseline and outbreak periods. We aimed to identify characteristics of notified cases that allow risk stratification in order to improve the efficiency of the public health response in an outbreak setting. METHODS: Retrospective descriptive case series for all measles notifications made to the Victorian Government Department of Health between 1 August and 30 September 2013. RESULTS: A total of 151 notifications were included in the analyses, of which 17 (11%) were confirmed as measles. Applying the clinical criteria of the measles case definition or identifying susceptible cases (determined by vaccination status) correctly identified all measles cases. Requiring cases to meet both criteria reduced sensitivity to 88%, but improved the positive predictive value (48% vs 25%) and retained a high negative predictive value (98.33%). Application of a risk stratification approach based on these features would have saved intensive public health follow-up for 79.5% of notifications in this outbreak. CONCLUSIONS: Immune status and clinical features can reliably be used to predict which notifications are unlikely to become confirmed cases. IMPLICATIONS: Risk stratification and modification of current surveillance practices may provide for a more efficient public health response, particularly during periods of increased case notification. PMID- 27198178 TI - Piperlongumine inhibits lung tumor growth via inhibition of nuclear factor kappa B signaling pathway. AB - Piperlongumine has anti-cancer activity in numerous cancer cell lines via various signaling pathways. But there has been no study regarding the mechanisms of PL on the lung cancer yet. Thus, we evaluated the anti-cancer effects and possible mechanisms of PL on non-small cell lung cancer (NSCLC) cells in vivo and in vitro. Our findings showed that PL induced apoptotic cell death and suppressed the DNA binding activity of NF-kappaB in a concentration dependent manner (0-15 MUM) in NSCLC cells. Docking model and pull down assay showed that PL directly binds to the DNA binding site of nuclear factor-kappaB (NF-kappaB) p50 subunit, and surface plasmon resonance (SPR) analysis showed that PL binds to p50 concentration-dependently. Moreover, co-treatment of PL with NF-kappaB inhibitor phenylarsine oxide (0.1 MUM) or p50 siRNA (100 nM) augmented PL-induced inhibitory effect on cell growth and activation of Fas and DR4. Notably, co treatment of PL with p50 mutant plasmid (C62S) partially abolished PL-induced cell growth inhibition and decreased the enhanced expression of Fas and DR4. In xenograft mice model, PL (2.5-5 mg/kg) suppressed tumor growth of NSCLC dose dependently. Therefore, these results indicated that PL could inhibit lung cancer cell growth via inhibition of NF-kappaB signaling pathway in vitro and in vivo. PMID- 27198179 TI - Molecular evolutionary rates are not correlated with temperature and latitude in Squamata: an exception to the metabolic theory of ecology? AB - BACKGROUND: The metabolic theory of ecology stipulates that molecular evolutionary rates should correlate with temperature and latitude in ectothermic organisms. Previous studies have shown that most groups of vertebrates, such as amphibians, turtles and even endothermic mammals, have higher molecular evolutionary rates in regions where temperature is high. However, the association between molecular evolutionary rates and temperature or latitude has never been tested in Squamata. RESULTS: We used a large dataset including the spatial distributions and environmental variables for 1,651 species of Squamata and compared the contrast of the rates of molecular evolution with the contrast of temperature and latitude between sister species. Using major axis regressions and a new algorithm to choose independent sister species pairs, we found that temperature and absolute latitude were not associated with molecular evolutionary rates. CONCLUSIONS: This absence of association in such a diverse ectothermic group questions the mechanisms explaining current pattern of species diversity in Squamata and challenges the presupposed universality of the metabolic theory of ecology. PMID- 27198180 TI - A reversible B-A transition of DNA duplexes induced by synthetic cationic copolymers. AB - Although the B-form duplex is the canonical DNA structure, the A-form duplex plays critical roles in controlling gene expression. Here, reversible B-A transitions of DNA duplexes were induced by synthetic cationic and anionic polymers. Thermodynamic analysis demonstrated that the B-A transition was regulated by the dehydration of the DNA duplex caused by polymer binding. PMID- 27198181 TI - The Crystal Structure of Burkholderia cenocepacia DfsA Provides Insights into Substrate Recognition and Quorum Sensing Fatty Acid Biosynthesis. AB - Burkholderia cenocepacia is a major concern among respiratory tract infections in cystic fibrosis patients. This pathogen is particularly difficult to treat because of its high level of resistance to the clinically relevant antimicrobial agents. In B. cenocepacia, the quorum sensing cell-cell communication system is involved in different processes that are important for bacterial virulence, such as biofilm formation and protease and siderophore production. Targeting the enzymes involved in this process represents a promising therapeutic approach. With the aim of finding effective quorum sensing inhibitors, we have determined the three-dimensional structure of B. cenocepacia diffusible factor synthase A, DfsA. This bifunctional crotonase (dehydratase/thioesterase) produces the characteristic quorum sensing molecule of B. cenocepacia, cis-2-dodecenoic acid or BDSF, starting from 3-hydroxydodecanoyl-acyl carrier protein. Unexpectedly, the crystal structure revealed the presence of a lipid molecule in the catalytic site of the enzyme, which was identified as dodecanoic acid. Our biochemical characterization shows that DfsA is able to use dodecanoyl-acyl carrier protein as a substrate, demonstrating that dodecanoic acid, the product of this reaction, is released very slowly from the DfsA active site, therefore acting as a DfsA inhibitor. This molecule shows an unprecedented conformational arrangement inside the DfsA active site. In contrast with previous hypotheses, our data illustrate how DfsA and closely related homologous enzymes can recognize long hydrophobic substrates without large conformational changes or assistance by additional regulator molecules. The elucidation of the substrate binding mode in DfsA provides the starting point for structure-based drug discovery studies targeting B. cenocepacia quorum sensing-assisted virulence. PMID- 27198183 TI - Hospital Evacuation and Shelter-in-Place: Who Is Responsible for Decision-Making? AB - OBJECTIVE: During natural disasters, hospital evacuation may be necessary to ensure patient safety and care. We aimed to examine perceptions of stakeholders involved in these decisions throughout the Mid-Atlantic region of the United States during Hurricane Sandy in October 2012. METHODS: Semistructured interviews were conducted from March 2014 to February 2015 to characterize stakeholders' perceptions about authority and responsibility for acute care hospital evacuation/shelter-in-place decision-making in Delaware, Maryland, New Jersey, and New York during Hurricane Sandy. Interviews were recorded, transcribed, and thematically analyzed using a framework approach. RESULTS: We interviewed 42 individuals from 32 organizations. Hospital executives from all states reported having authority and responsibility for evacuation/shelter-in-place decision making. In New York and Maryland, government officials stated that they could order hospital evacuation, whereas officials in Delaware and New Jersey said the government lacked enforcement capacity and therefore could not mandate evacuation. CONCLUSIONS: Among government officials, perceived authority for hospital evacuation/shelter-in-place decision-making was viewed as a prerequisite to ordering evacuation. When both hospital executives and government officials perceive themselves to possess decision-making authority, there is the potential for inaction. Future work should examine whether a single entity bearing ultimate responsibility or regional emergency response coalitions would improve decision making. (Disaster Med Public Health Preparedness. 2016;10:320-324). PMID- 27198182 TI - Fly DPP10 acts as a channel ancillary subunit and possesses peptidase activity. AB - Mammalian DPP6 (DPPX) and DPP10 (DPPY) belong to a family of dipeptidyl peptidases, but lack enzyme activity. Instead, these proteins form complexes with voltage-gated K(+) channels in Kv4 family to control their gating and other properties. Here, we find that the fly DPP10 ortholog acts as an ancillary subunit of Kv4 channels and digests peptides. Similarly to mammalian DPP10, the fly ortholog tightly binds to rat Kv4.3 protein. The association causes negative shifts in voltage dependence of channel activation and steady state inactivation. It also results in faster inactivation and recovery from inactivation. In addition to its channel regulatory role, fly DPP10 exhibits significant dipeptidyl peptidase activity with Gly-Pro-MCA (glycyl-L-proline 4-methylcoumaryl 7-amide) as a substrate. Heterologously expressed Flag-tagged fly DPP10 and human DPP4 show similar Km values towards this substrate. However, fly DPP10 exhibits approximately a 6-times-lower relative kcat value normalized with anti-Flag immunoreactivity than human DPP4. These results demonstrate that fly DPP10 is a dual functional protein, controlling Kv4 channel gating and removing bioactive peptides. PMID- 27198184 TI - Remodeling of Neuronal Circuits After Reach Training in Chronic Capsular Stroke. AB - BACKGROUND: Subcortical capsular stroke has a poor prognosis, and it is not yet fully understood how and under what circumstances reach training contributes to motor recovery. Objective This study was performed to investigate changes in neuronal circuits and motor recovery in a chronic capsular stroke model in the presence or absence of reach training. METHOD: We generated photothrombotic capsular lesions in 42 Sprague-Dawley rats and evaluated motor recovery with or without daily training in a single-pellet reaching task (SPRT). We used 2-deoxy-2 [18F]-fluoro-D-glucose-microPET (positron emission tomography) to assess remodeling of neuronal circuits. RESULTS: SPRT training was selectively beneficial only for the group with incomplete capsular destruction (P < .05), suggesting the relevance of plasticity in the remaining capsular fibers for motor recovery. Groups that did not receive SPRT training showed no motor recovery at all. The microPET analysis demonstrated that motor recovery was correlated with a reduction in cortical diaschisis in ipsilesional motor and sensory cortices and in the contralesional sensory cortex (Pearson's correlation, P < .05). We also observed training-dependent subcortical activation in the contralesional red nucleus, the internal capsule, and the ventral hippocampus (P < .0025; false discovery rate q < 0.05). The groups without reach training did not show the same degree of reduction in diaschisis or activation of the red nucleus. CONCLUSIONS: Our results suggest that motor recovery and remodeling of neuronal circuits after capsular stroke depend on the magnitude of the capsular lesion and on the presence or absence of reach training. Task-specific training is strongly indicated only when there is incomplete destruction of the capsular fibers. PMID- 27198186 TI - Biology and treatment of cervical adenocarcinoma. AB - Uterine cervical adenocarcinoma (ADC) has been increasing in its prevalence world widely despite the decrease of squamous cell carcinoma (SCC). It comprises nearly 20-25% of the all cervical malignancy in developed countries. The worse biological behavior had been reported in patients with intermediate- and high risk factors after surgery, and in advanced stage over III, radiotherapy (RT) alone and concurrent chemo-radiotherapy (CCRT) with cisplatin was not always effective. As for chemotherapy (CT), the induction CT has not established, as well. Further molecular targeted therapy (MTT) has been studied. The targets of oncogenic driver mutations were vascular endothelial growth factor (VEGF) in SCC, or tyrosine kinase (TK) of endothelial growth factor receptor 2 (EGFR2, Her2/neu) Ras-MAPK-ERK pathway. Bevacizumab (Bev, anti-VEGF monoclonal antibody) is considered as one of key agent with paclitaxel and carboplatin in SCC, but not for ADC. This article focuses on up-to-date knowledge of biology and possible specific therapeutic directions to explore in the management of cervical ADC. PMID- 27198185 TI - Engaging Cervical Spinal Cord Networks to Reenable Volitional Control of Hand Function in Tetraplegic Patients. AB - BACKGROUND: Paralysis of the upper limbs from spinal cord injury results in an enormous loss of independence in an individual's daily life. Meaningful improvement in hand function is rare after 1 year of tetraparesis. Therapeutic developments that result in even modest gains in hand volitional function will significantly affect the quality of life for patients afflicted with high cervical injury. The ability to neuromodulate the lumbosacral spinal circuitry via epidural stimulation in regaining postural function and volitional control of the legs has been recently shown. A key question is whether a similar neuromodulatory strategy can be used to improve volitional motor control of the upper limbs, that is, performance of motor tasks considered to be less "automatic" than posture and locomotion. In this study, the effects of cervical epidural stimulation on hand function are characterized in subjects with chronic cervical cord injury. OBJECTIVE: Herein we show that epidural stimulation can be applied to the chronic injured human cervical spinal cord to promote volitional hand function. METHODS AND RESULTS: Two subjects implanted with a cervical epidural electrode array demonstrated improved hand strength (approximately 3 fold) and volitional hand control in the presence of epidural stimulation. CONCLUSIONS: The present data are sufficient to suggest that hand motor function in individuals with chronic tetraplegia can be improved with cervical cord neuromodulation and thus should be comprehensively explored as a possible clinical intervention. PMID- 27198187 TI - Mycoprotein reduces energy intake and postprandial insulin release without altering glucagon-like peptide-1 and peptide tyrosine-tyrosine concentrations in healthy overweight and obese adults: a randomised-controlled trial. AB - Dietary mycoprotein decreases energy intake in lean individuals. The effects in overweight individuals are unclear, and the mechanisms remain to be elucidated. This study aimed to investigate the effect of mycoprotein on energy intake, appetite regulation, and the metabolic phenotype in overweight and obese volunteers. In two randomised-controlled trials, fifty-five volunteers (age: 31 (95 % CI 27, 35) years), BMI: 28.0 (95 % CI 27.3, 28.7) kg/m2) consumed a test meal containing low (44 g), medium (88 g) or high (132 g) mycoprotein or isoenergetic chicken meals. Visual analogue scales and blood samples were collected to measure appetite, glucose, insulin, peptide tyrosine-tyrosine (PYY) and glucagon-like peptide-1 (GLP-1). Ad libitum energy intake was assessed after 3 h in part A (n 36). Gastric emptying by the paracetamol method, resting energy expenditure and substrate oxidation were recorded in part B (n 14). Metabonomics was used to compare plasma and urine samples in response to the test meals. Mycoprotein reduced energy intake by 10 % (280 kJ (67 kcal)) compared with chicken at the high content (P=0.009). All mycoprotein meals reduced insulin concentrations compared with chicken (incremental AUClow (IAUClow): -8 %, IAUCmedium: -12 %, IAUChigh: -21 %, P=0.004). There was no significant difference in glucose, PYY, GLP-1, gastric emptying rate and energy expenditure. Following chicken intake, paracetamol-glucuronide was positively associated with fullness. After mycoprotein, creatinine and the deamination product of isoleucine, alpha keto-beta-methyl-N-valerate, were inversely related to fullness, whereas the ketone body, beta-hydroxybutyrate, was positively associated. In conclusion, mycoprotein reduces energy intake and insulin release in overweight volunteers. The mechanism does not involve changes in PYY and GLP-1. The metabonomics analysis may bring new understanding to the appetite regulatory properties of food. PMID- 27198188 TI - Spatial organization shapes the turnover of a bacterial transcriptome. AB - Spatial organization of the transcriptome has emerged as a powerful means for regulating the post-transcriptional fate of RNA in eukaryotes; however, whether prokaryotes use RNA spatial organization as a mechanism for post-transcriptional regulation remains unclear. Here we used super-resolution microscopy to image the E. coli transcriptome and observed a genome-wide spatial organization of RNA: mRNAs encoding inner-membrane proteins are enriched at the membrane, whereas mRNAs encoding outer-membrane, cytoplasmic and periplasmic proteins are distributed throughout the cytoplasm. Membrane enrichment is caused by co translational insertion of signal peptides recognized by the signal-recognition particle. Time-resolved RNA-sequencing revealed that degradation rates of inner membrane-protein mRNAs are on average greater that those of the other mRNAs and that this selective destabilization of inner-membrane-protein mRNAs is abolished by dissociating the RNA degradosome from the membrane. Together, these results demonstrate that the bacterial transcriptome is spatially organized and suggest that this organization shapes the post-transcriptional dynamics of mRNAs. PMID- 27198190 TI - Finding FISH in a small pond. AB - Advanced microscopy and labeling techniques reveal that bacteria localize mRNAs within their cells in a similar way to eukaryotes. PMID- 27198189 TI - Simple biophysics underpins collective conformations of the intrinsically disordered proteins of the Nuclear Pore Complex. AB - Nuclear Pore Complexes (NPCs) are key cellular transporter that control nucleocytoplasmic transport in eukaryotic cells, but its transport mechanism is still not understood. The centerpiece of NPC transport is the assembly of intrinsically disordered polypeptides, known as FG nucleoporins, lining its passageway. Their conformations and collective dynamics during transport are difficult to assess in vivo. In vitro investigations provide partially conflicting results, lending support to different models of transport, which invoke various conformational transitions of the FG nucleoporins induced by the cargo-carrying transport proteins. We show that the spatial organization of FG nucleoporin assemblies with the transport proteins can be understood within a first principles biophysical model with a minimal number of key physical variables, such as the average protein interaction strengths and spatial densities. These results address some of the outstanding controversies and suggest how molecularly divergent NPCs in different species can perform essentially the same function. PMID- 27198192 TI - Mucosal integrity and sensitivity to acid in the proximal esophagus in patients with gastroesophageal reflux disease. AB - Acid reflux episodes that extend to the proximal esophagus are more likely to be perceived. This suggests that the proximal esophagus is more sensitive to acid than the distal esophagus, which could be caused by impaired mucosal integrity in the proximal esophagus. Our aim was to explore sensitivity to acid and mucosal integrity in different segments of the esophagus. We used a prospective observational study, including 12 patients with gastroesophageal reflux disease (GERD). After stopping acid secretion-inhibiting medication, two procedures were performed: an acid perfusion test and an upper endoscopy with electrical tissue impedance spectroscopy and esophageal biopsies. Proximal and distal sensitivity to acid and tissue impedance were measured in vivo, and mucosal permeability and epithelial intercellular spaces at different esophageal levels were measured in vitro. Mean lag time to heartburn perception was much shorter after proximal acid perfusion (0.8 min) than after distal acid perfusion (3.9 min) (P = 0.02). Median in vivo tissue impedance was significantly lower in the distal esophagus (4,563 Omega.m) compared with the proximal esophagus (8,170 Omega.m) (P = 0.002). Transepithelial permeability, as measured by the median fluorescein flux was significantly higher in the distal (2,051 nmol.cm(-2).h(-1)) than in the proximal segment (368 nmol.cm(-2).h(-1)) (P = 0.033). Intercellular space ratio and maximum heartburn intensity were not significantly different between the proximal and distal esophagus. In GERD patients off acid secretion-inhibiting medication, acid exposure in the proximal segment of the esophagus provokes symptoms earlier than acid exposure in the distal esophagus, whereas mucosal integrity is impaired more in the distal esophagus. These findings indicate that the enhanced sensitivity to proximal reflux episodes is not explained by increased mucosal permeability. PMID- 27198191 TI - Night workers with circadian misalignment are susceptible to alcohol-induced intestinal hyperpermeability with social drinking. AB - Alcohol-induced intestinal hyperpermeability (AIHP) is a known risk factor for alcoholic liver disease (ALD), but only 20-30% of heavy alcoholics develop AIHP and ALD. The hypothesis of this study is that circadian misalignment would promote AIHP. We studied two groups of healthy subjects on a stable work schedule for 3 mo [day workers (DW) and night workers (NW)]. Subjects underwent two circadian phase assessments with sugar challenge to access intestinal permeability between which they drank 0.5 g/kg alcohol daily for 7 days. Sleep architecture by actigraphy did not differ at baseline or after alcohol between either group. After alcohol, the dim light melatonin onset (DLMO) in the DW group did not change significantly, but in the NW group there was a significant 2-h phase delay. Both the NW and DW groups had no change in small bowel permeability with alcohol, but only in the NW group was there an increase in colonic and whole gut permeability. A lower area under the curve of melatonin inversely correlated with increased colonic permeability. Alcohol also altered peripheral clock gene amplitude of peripheral blood mononuclear cells in CLOCK, BMAL, PER1, CRY1, and CRY2 in both groups, and inflammatory markers lipopolysaccharide-binding protein, LPS, and IL-6 had an elevated mesor at baseline in NW vs. DW and became arrhythmic with alcohol consumption. Together, our data suggest that central circadian misalignment is a previously unappreciated risk factor for AIHP and that night workers may be at increased risk for developing liver injury with alcohol consumption. PMID- 27198193 TI - A human model of restricted upper esophageal sphincter opening and its pharyngeal and UES deglutitive pressure phenomena. AB - Oropharyngeal dysphagia due to upper esophageal sphincter (UES) dysfunction is commonly encountered in the clinical setting. Selective experimental perturbation of various components of the deglutitive apparatus can provide an opportunity to improve our understanding of the swallowing physiology and pathophysiology. The aim is to characterize the pharyngeal and UES deglutitive pressure phenomena in an experimentally induced restriction of UES opening in humans. We studied 14 volunteers without any dysphagic symptoms (7 men, 66 +/- 11 yr) but with various supraesophageal reflux symptoms. To induce UES restriction, we used a handmade device that with adjustment could selectively apply 0, 20, 30, or 40 mmHg pressure perpendicularly to the cricoid cartilage. Deglutitive pharyngeal and UES pressure phenomena were determined during dry and 5- and 10-ml water swallows * 3 for each of the UES perturbations. External cricoid pressure against the UES resulted in a significant increase in hypopharyngeal intrabolus pressure and UES nadir deglutitive relaxation pressure for all tested swallowed volumes (P < 0.05). Application of external cricoid pressure increased the length of the UES high pressure zone from 2.5 +/- 0.2 to 3.1 +/- 0.2, 3.5 +/- 0.1, and 3.7 +/- 0.1 cm for 20, 30, and 40 mmHg cricoid pressure, respectively (P < 0.05). External cricoid pressure had no significant effect on pharyngeal peristalsis. On the other hand, irrespective of external cricoid pressure deglutitive velopharyngeal contractile integral progressively increased with increased swallowed volumes (P < 0.05). In conclusion, acute experimental restriction of UES opening by external cricoid pressure manifests the pressure characteristics of increased resistance to UES transsphincteric flow observed clinically without affecting the pharyngeal peristaltic contractile function. PMID- 27198194 TI - Role of ion transporters in the bile acid-induced esophageal injury. AB - Barrett's esophagus (BE) is considered to be the most severe complication of gastro-esophageal reflux disease (GERD), in which the prolonged, repetitive episodes of combined acidic and biliary reflux result in the replacement of the squamous esophageal lining by columnar epithelium. Therefore, the acid-extruding mechanisms of esophageal epithelial cells (EECs) may play an important role in the defense. Our aim was to identify the presence of acid/base transporters on EECs and to investigate the effect of bile acids on their expressions and functions. Human EEC lines (CP-A and CP-D) were acutely exposed to bile acid cocktail (BAC) and the changes in intracellular pH (pHi) and Ca(2+) concentration ([Ca(2+)]i) were measured by microfluorometry. mRNA and protein expression of ion transporters was investigated by RT-PCR, Western blot, and immunohistochemistry. We have identified the presence of a Na(+)/H(+) exchanger (NHE), Na(+)/HCO3 (-) cotransporter (NBC), and a Cl(-)-dependent HCO3 (-) secretory mechanism in CP-A and CP-D cells. Acute administration of BAC stimulated HCO3 (-) secretion in both cell lines and the NHE activity in CP-D cells by an inositol triphosphate dependent calcium release. Chronic administration of BAC to EECs increased the expression of ion transporters compared with nontreated cells. A similar expression pattern was observed in biopsy samples from BE compared with normal epithelium. We have shown that acute administration of bile acids differently alters ion transport mechanisms of EECs, whereas chronic exposure to bile acids increases the expression of acid/base transporters. We speculate that these adaptive processes of EECs represent an important mucosal defense against the bile acid-induced epithelial injury. PMID- 27198195 TI - Multidetector computed tomography shows reverse cardiac remodeling after double lung transplantation for pulmonary hypertension. AB - OBJECTIVE: To use multidetector computed tomography (MDCT) to evaluate the structural changes in the right heart and pulmonary arteries that occur in patients with severe pulmonary hypertension treated by double lung transplantation. MATERIAL AND METHODS: This was a retrospective study of 21 consecutive patients diagnosed with severe pulmonary hypertension who underwent double lung transplantation at our center between 2010 and 2014. We analyzed the last MDCT study done before lung transplantation and the first MDCT study done after lung transplantation. We recorded the following variables: diameter of the pulmonary artery trunk, ratio of the diameter of the pulmonary artery trunk to the diameter of the ascending aorta, diameter of the right ventricle, ratio of the diameter of the left ventricle to the diameter of the right ventricle, and eccentricity index. Statistical analysis consisted of the comparison of the means of the variables recorded. RESULTS: In all cases analyzed, the MDCT study done a mean of 24+/-14 days after double lung transplantation showed a significant reduction in the size of the right heart chambers, with improved indices of ventricular interdependency index, and reduction in the size of the pulmonary artery trunk (p<0.001 for all the variables analyzed). CONCLUSION: Patients with pulmonary hypertension treated by double lung transplantation present early reverse remodeling of the changes in the structures of the right heart and pulmonary arterial tree. MDCT is useful for detecting these changes. PMID- 27198197 TI - Physician assistants in Australasian emergency departments. AB - A physician assistant (PA) is a university qualified health professional who's primary role is to provide medical care under the direction and supervision of medical staff. This is a new profession in Australasia. The PA is well suited to working in both rural, regional and urban settings that deliver emergency medical care. A perspective is presented on their role and scope of practice within the Australasian emergency care system supported by some early findings from their use in a tertiary ED. PMID- 27198198 TI - Fibroadhesive peritoneal tuberculosis mimicking inflammatory acute abdomen due to appendiceal adhesions. PMID- 27198199 TI - Valentino's syndrome. Perforated peptic ulcer with unusual clinical presentation. PMID- 27198200 TI - An uncommon cause of epigastralgia. PMID- 27198196 TI - Gut environment-induced intraepithelial autoreactive CD4(+) T cells suppress central nervous system autoimmunity via LAG-3. AB - The gut environment has been found to significantly influence autoimmune diseases such as multiple sclerosis; however, immune cell mechanisms are unclear. Here we show that the gut epithelium of myelin oligodendrocyte glycoprotein(35-55) specific T-cell receptor transgenic mice contains environmental stimuli-induced intraepithelial lymphocytes (IELs) that inhibit experimental autoimmune encephalomyelitis on transfer. These cells express surface markers phenotypical of 'induced' IELs, have a TH17-like profile and infiltrate the central nervous system (CNS). They constitutively express Ctla4 and Tgfb1 and markedly upregulate Lag3 expression in the CNS, thereby inhibiting inflammation. We also demonstrate the suppressive capability of CD4(+) IELs with alternative antigen specificities, their proliferation in response to gut-derived antigens and contribution of the microbiota and dietary aryl hydrocarbon receptor ligands to their induction. Thus, the gut environment favours the generation of autoreactive CD4(+) T cells with unique regulatory functions, potentially important for preventing CNS autoimmunity. PMID- 27198201 TI - Intra-abdominal synovial sarcoma. PMID- 27198202 TI - Probing protein complexes inside living cells using a silicon nanowire-based pull down assay. AB - Most proteins perform their functions as interacting complexes. Here we propose a novel method for capturing an intracellular protein and its interacting partner out of living cells by utilizing intracellular access of antibody modified vertical silicon nanowire arrays whose surface is covered with a polyethylene glycol layer to prevent strong cell adhesion. Such a feature facilitates the removal of cells by simple washing, enabling subsequent detection of a pulled down protein and its interacting partner, and further assessment of a drug induced change in the interacting complex. Our new SiNW-based tool is thus suitable for authentication of protein networks inside living cells. PMID- 27198203 TI - Waste polyethylene terephthalate (PET) materials as sustainable precursors for the synthesis of nanoporous MOFs, MIL-47, MIL-53(Cr, Al, Ga) and MIL-101(Cr). AB - In our novel green approach, the waste polyethylene terephthalate (PET) bottle material has effectively been used as the starting precursor instead of terephthalic acid for the synthesis of five terephthalate based nanoporous trivalent metal-organic frameworks (MOFs) namely MIL-47, MIL-53(Cr), MIL-53(Al), MIL-53(Ga), and MIL-101(Cr). The optimum reaction parameters to achieve the green synthesis were studied. These MOFs were structurally identified by using powder X ray diffraction (PXRD) measurements. Scanning electron microscopy (SEM) images confirm the particle nature and size of the synthesized MOFs. Nitrogen gas sorption measurements have been done for some of the MOFs to check their porous properties. All the characterization techniques strongly supported that the synthesized MOFs using PET are similar to their literature reports. The gas adsorption studies for the synthesized MIL-53(Cr) and MIL-101(Cr) showed their significant gas uptake capability towards CO2 and H2 gases. Further, the synthesized MIL-47 and MIL-101(Cr) have been tested for their catalytic ability in chemical fixation of CO2 gas through the conversion of CO2 and epoxides to the corresponding cyclic carbonates which shows promising results to use them as catalysts. PMID- 27198204 TI - Distinct genetic evolution patterns of relapsing diffuse large B-cell lymphoma revealed by genome-wide copy number aberration and targeted sequencing analysis. AB - Recurrences of diffuse large B-cell lymphomas (DLBCL) result in significant morbidity and mortality, but their underlying genetic and biological mechanisms are unclear. Clonal relationship in DLBCL relapses so far is mostly addressed by the investigation of immunoglobulin (IG) rearrangements, therefore, lacking deeper insights into genome-wide lymphoma evolution. We studied mutations and copy number aberrations in 20 paired relapsing and 20 non-relapsing DLBCL cases aiming to test the clonal relationship between primaries and relapses to track tumors' genetic evolution and to investigate the genetic background of DLBCL recurrence. Three clonally unrelated DLBCL relapses were identified (15%). Also, two distinct patterns of genetic evolution in clonally related relapses were detected as follows: (1) early-divergent/branching evolution from a common progenitor in 6 patients (30%), and (2) late-divergent/linear progression of relapses in 11 patients (65%). Analysis of recurrent genetic events identified potential early drivers of lymphomagenesis (KMT2D, MYD88, CD79B and PIM1). The most frequent relapse-specific events were additional mutations in KMT2D and alterations of MEF2B. SOCS1 mutations were exclusive to non-relapsing DLBCL, whereas primaries of relapsing DLBCL more commonly displayed gains of 10p15.3 p12.1 containing the potential oncogenes PRKCQ, GATA3, MLLT10 and ABI1. Altogether, our study expands the knowledge on clonal relationship, genetic evolution and mutational basis of DLBCL relapses. PMID- 27198205 TI - Impact of parathyroidectomy for primary hyperparathyroidism on quality of life: A case-control study using Short Form Health Survey 36. AB - BACKGROUND: Physical and mental complaints are common in patients with primary hyperparathyroidism (PHPT) and negatively impact quality of life (QOL). Subjective symptoms in current guidelines are not considered an indication for surgery. The purpose of this study was to assess the effect of parathyroidectomy on QOL in patients with PHPT. METHODS: This multicenter case-control study investigated preoperative and postoperative QOL scores in patients operated for PHPT, measured with the Short Form Health Survey-36 (SF-36) questionnaire. Results were compared with patients undergoing a hemithyroidectomy, the control group. RESULTS: Fifty-two patients and 49 controls were included. Patients with PHPT had significantly lower QOL scores preoperatively and improved significantly after successful surgical treatment. Postoperatively, no differences were observed between the 2 groups. CONCLUSION: QOL was significantly lower in patients with untreated PHPT. Surgical treatment was associated with a significant increase in QOL. Decreased QOL should also be considered as an indicator for surgical treatment in patients with PHPT. (c) 2016 Wiley Periodicals, Inc. Head Neck 38:1213-1220, 2016. PMID- 27198206 TI - Reconstruction of the severely atrophic edentulous maxillae with calvarial bone grafts. AB - OBJECTIVES: Treatment of the severely atrophic maxilla with dental implants is challenging due to the insufficient horizontal and vertical bone volume and centripetal resorption pattern of the maxilla. Bone-augmentation procedures are often necessary prior to implant placement. The objective of this study was to assess the suitability of using calvarial bone grafts to enable implant placement in severely atrophic maxillae. MATERIAL AND METHODS: Seventeen patients with severe atrophic edentulous maxillae were reconstructed with autogenous calvarial bone grafts. After a 4-month healing period, the patients received a total of 134 dental implants, which were left to heal in submerged positions for 3 months before prosthetic rehabilitation was performed. Patients were followed clinically and radiographically for an average observation period of 53.94 months. RESULTS: At the intraoral recipient sites, two infections developed, causing partial loss of the respective bone grafts. Implant placement, however, was possible at all sites. No donor-site complications occurred. Two of 134 implants were lost in two patients prior to prosthetic loading. The implant survival rate was 98.51%. The implant success rate was 87.6%, and a mean marginal bone loss of 0.62 mm (SD 0.77 mm) was documented. CONCLUSIONS: Patients with severe bone atrophy of the edentulous maxilla can be successfully reconstructed with calvarial bone grafts and dental implants and show a stable clinical and radiographic situation after a mean observation period of 53 months. PMID- 27198207 TI - Multigene and Drug Interaction Approach for Tamoxifen Metabolite Patterns Reveals Possible Involvement of CYP2C9, CYP2C19, and ABCB1. AB - Tamoxifen is metabolically activated to 4-hydroxytamoxifen and endoxifen by cytochrome P450 (CYP). CYP phenotypes have been correlated to tamoxifen outcomes, but few have considered drug interactions or combinations of genes. Fewer still have considered ABCB1, which encodes P-glycoprotein and transports active tamoxifen metabolites. We compared the concentrations of tamoxifen and metabolites in 116 breast cancer patients with predicted phenotypes for CYP2D6, CYP3A4, CYP3A5, CYP2C9, CYP2C19, and ABCB1 genotypes. A significant correlation between CYP2D6 phenotypes and tamoxifen metabolites was seen, strongest for endoxifen (P < .0001). Statistical fit of the data improved when using gene activity scores adjusted for known drug interactions. Concentration of tamoxifen was significantly higher (P = .02) for patients taking a CYP2C19 inhibitor. No significant relationships were found for other genes unless patients were subgrouped according to CYP2D6 phenotypes or ABCB1 genotypes. Lower concentrations of endoxifen and endoxifen/4-hydroxytamoxifen ratios were seen with impaired CYP2C9 (P = .05 and P = .03, respectively) if patients had the same CYP2D6 phenotype and were not taking a CYP2D6 or CYP2C19 inhibitor. Lower concentrations of 4-hydroxytamoxifen were seen for impaired CYP2C19 when ABCB1 SNP3435 was nonvariant (P = .04). With 3 impaired CYP phenotypes, endoxifen concentrations were lower than if only CYP2D6 was impaired (P = .05). When CYP2D6 was impaired, ABCB1 3435 CC (rs1045642) was associated with significantly higher endoxifen (P = .03). Thus, impairment in CYP2C9, CYP2C19, or ABCB1 contributes to a lower steady-state endoxifen concentration at the dose studied. These studies represent an improved way of examining relationships between pharmacogenetics, drug concentrations, and clinical outcomes and warrants study in larger populations. PMID- 27198208 TI - Diabetes in the tropics: prevalent, increasing and a major public health problem. PMID- 27198209 TI - Shared sanitation: to include or to exclude? AB - Just over 600 million people used shared sanitation in 2015, but this form of sanitation is not considered 'improved sanitation' or, in the current terminology, 'basic sanitation' by WHO/UNICEF, principally because they are typically unhygienic. Recent research has shown that neighbour-shared toilets perform much better than large communal toilets. The successful development of community-designed, built and managed sanitation-and-water blocks in very poor urban areas in India should be adapted and adopted throughout urban slums in developing countries, with a caretaker employed to keep the facilities clean. Such shared sanitation should be classified as 'basic', sometimes as 'safely managed', sanitation, so contributing to the achievement of the sanitation target of the Sustainable Development Goals. PMID- 27198210 TI - Systematic review of risk factors for nonadherence to TB treatment in immigrant populations. AB - BACKGROUND: Foreign-born populations carry a significant TB burden in low prevalence countries, composing over half of all cases in parts of Europe and North America. This study systematically reviewed evidence of risk factors for nonadherence to TB drug therapy in this group. METHODS: On 28 October 2013 MEDLINE, CINAHL, Embase, PsychINFO and ProQuest were systematically searched for studies examining adherence in foreign-born populations with TB. Grey literature and reference lists were hand-searched. Risk factor studies were selected for inclusion if they consisted of at least 95% foreign-born populations. RESULTS: Of 1761 studies identified in the search, 20 were included in the risk factor review. Undocumented immigration status, older age, and social risk factors were consistently correlated with nonadherence; gender, ethnicity, immigration time, education level, adverse side effects, and HIV status were inconsistently correlated; and behavioural risk factors and marital status were consistently not correlated. CONCLUSIONS: This review emphasizes documentation status as a risk factor candidate for further investigation. PMID- 27198211 TI - Quantitative and volume, conductivity and scatter changes in leucocytes of patients with acute undifferentiated febrile illness: a pilot study. AB - BACKGROUND: A single diagnostic test for acute undifferentiated febrile illnesses (AUFI) is elusive. This pilot study was undertaken on the premise that leucocytes, being the main cells of defence, undergo quantitative, structural and functional changes in AUFI. We evaluated the potential of volume, conductivity and scatter (VCS) parameters of leucocytes, generated with the haemogram report by the Coulter auto-analyzer, in differentiating the common etiologies of AUFI. METHODS: The haematological and VCS data obtained from 800 controls and 200 cases of AUFI (50 cases each of acute malaria, dengue, scrub typhus and enteric fever) were retrieved for analysis. RESULTS: The cases and controls differed significantly with respect to relative numbers and the VCS parameters of neutrophils, lymphocytes and monocytes (p<0.05). The neutrophil and lymphocyte were significantly voluminous in acute malaria and scrub typhus as compared to dengue and enteric fevers (p<0.05). Enteric fever significantly enhanced the conductivity of neutrophils as compared to other subgroups while lymphocyte conductivity significantly differed from dengue and scrub typhus. Lymphocyte and neutrophil scatter values in malaria and scrub typhus were comparable but differed significantly from that in enteric fever. CONCLUSIONS: Etiology-specific changes occur in leucocytes, both in numbers and their VCS properties which can be identified without additional cost. PMID- 27198212 TI - Detection of Leishmania donovani in peripheral blood of asymptomatic individuals in contact with patients with visceral leishmaniasis. AB - BACKGROUND: The majority of individuals infected with Leishmania donovani complex remain asymptomatic. They may act as transmission reservoirs for visceral leishmaniasis (VL). We investigated sero-prevalence of L. donovani complex amongst those closely associated with patients with VL and whether these sero reactive individuals had Leishmania parasites in their peripheral blood. Other risk factors were also investigated. METHODS: A total of 257 individuals in contact with patients with VL were tested for anti-Leishmania antibodies by rK39 immunochromatographic test (rK39 ICT), ELISA using promastigote antigen (p-ELISA) and indirect fluorescent antibody test (IFAT). Buffy coats of rK39 ICT positive individuals were cultured; sero-reactive buffy coats were tested for Leishmania DNA by ITS1 PCR. DNA obtained from culture was sequenced to confirm Leishmania species. Risk factors were evaluated for each sero-positive sample. RESULTS: The results showed 29.2% (75/257) prevalence by serological tests: 14.4% (37/257) were positive by rK39 ICT, 25.3% (65/257) by p-ELISA, 18.3% (47/257) by IFAT and 10.9% (28/257) by all three serological methods. Ten percent (3/30) of cultures were positive for Leishmania promastigotes. Only 3% (2/74) sero-reactive buffy coats were positive for DNA; sequence analysis revealed L. donovani species. Significant risk factors were age, working as farmers, domestic animals in household and proximity to animal shelters. CONCLUSIONS: Asymptomatic family members of patients with VL can carry live L. donovani in peripheral blood and may act as potential reservoirs. GENBANK ACCESSION NUMBER: BankIt1863680 Leishmania KT921417 (DNA sequences of the ribosomal ITS1 region of L. donovani). PMID- 27198213 TI - Possible selection of host folate pathway gene polymorphisms in patients with malaria from a malaria endemic region in North East India. AB - BACKGROUND: Recent studies in experimental mice have shown that mild deficiency of methylenetetrahydrofolate reductase (MTHFR) enzyme confers protection against malaria, thus providing an important basis for the hypothesis that MTHFR polymorphism, i.e. C677T, might have been subjected to selection pressure against malaria. The present study was undertaken in a malaria endemic region in North East India to assess whether a similar selection advantage exists for other genes in folate metabolism pathway. METHODS: A total of 401 subjects including 131 symptomatic malaria, 97 asymptomatic malaria and 173 normal healthy controls were analysed for nine polymorphisms (single-nucleotide polymorphisms [SNPs] in eight genes and insertion/deletion in one gene): MTHFR C677T, methionine synthase reductase (MTRR) A66G, glutamate carboxypeptidase II (GCPII) C1561T, cystathionine beta-synthase (CBS) 844ins68, reduced folate carrier-1 (RFC-1) G80A, serine hydroxymethyltransferase (SHMT) C1420T, methionine synthase (MTR) A2756G, MTHFR G1793A (D 919G), glycine N-methyltransferase (GNMT) 1289 by PCR RFLP technique. Differences in frequencies of genotype distribution of each polymorphic marker between these groups were evaluated. RESULTS: MTRR A2756G, SHMT C1420T, GCPII C1561T, MTRR A2756G and GNMT C1289T and RFC1 G80A polymorphisms showed significantly different prevalence between different groups analyzed. No significant differences were seen in the distribution of other polymorphisms. CONCLUSIONS: The study gives a clue for the possible selection of specific polymorphisms in the genes involved in the folate metabolism pathway by malaria parasite. PMID- 27198214 TI - Rickettsia species in human-parasitizing ticks in Greece. AB - BACKGROUND: Ticks serve as vectors and reservoirs for a variety of bacterial, viral and protozoan pathogens affecting humans and animals. Unusual increased tick aggressiveness was observed in 2008-2009 in northeastern Greece. The aim of the study was to check ticks removed from persons during 2009 for infection with Rickettsia species. METHODS: A total of 159 ticks were removed from 147 persons who sought medical advice in a hospital. Tick identification was performed morphologically using taxonomic keys. DNA was extracted from each individual tick and a PCR assay targeting the rickettsial outer membrane protein A gene of Rickettsia spp. was applied. RESULTS: Most of the adult ticks (132/153, 86.3%) were Rhipicephalus sanguineus. Rickettsiae were detected in 23 of the 153 (15.0%) adult ticks. Five Rickettsiae species were identified: R. aeschlimannii, R. africae (n=6), R. massilae (4), R. monacensis (1), and Candidatus R. barbariae (1). To our knowledge, this is the first report of R. africae, R. monacensis, and Candidatus R. barbariae in Greece. CONCLUSIONS: Several Rickettsia species were identified in ticks removed from humans in Greece, including those that are prevalent in northern and southern latitudes. PMID- 27198217 TI - Understanding the relationship between prevalence of microfilariae and antigenaemia using a model of lymphatic filariasis infection. PMID- 27198215 TI - Policy to practice: impact of GeneXpert MTB/RIF implementation on the TB spectrum of care in Lilongwe, Malawi. AB - BACKGROUND: While previous research has provided evidence of the diagnostic accuracy of the GeneXpert MTB/RIF (GeneXpert), further information is needed about implementation in the real-world. This study evaluated the impact of the introduction of GeneXpert testing in a tertiary medical center according to the testing algorithm proposed by the National TB Control Program (NTP) guidelines. METHODS: All adult medicine inpatient persons with presumptive TB admitted between November 2013 and March 2014 were eligible for GeneXpert sputum testing and followed to TB treatment initiation status. RESULTS: We identified 932 persons with presumptive TB, of which 307 (32.9%) were GeneXpert tested. Those tested had an average age of 40 years, 49.2% (151) were male, 34.5% (106) were HIV positive, and 84.1% (249) presented with a cough. Of those GeneXpert tested, 28/307 (9.1%) tested positive, a 55.5% increase in detection compared to smear microscopy. However, the majority (44/72, 61%) of TB diagnoses were made by other modalities and not confirmed microbiologically. Of the 58 patients recommended to start treatment and discharged from the hospital, only 23 (40%) were documented to have started treatment at regional directly observed treatment short (DOTS) centers. CONCLUSIONS: GeneXpert contributed minimally to overall TB diagnosis and the cascade of care due to implementation challenges of sputum collection, empiric treatment, and weak linkage to care between inpatient and outpatient settings. PMID- 27198216 TI - Use of immunoblotting in testing Madurella mycetomatis specific antigen. AB - BACKGROUND: Though serodiagnosis of actinomycetoma is established, that of eumycetoma due to Madurella mycetomatis is limited because of lack of pure antigen. Reliable rapid tests are needed to make an accurate timely diagnosis. The purpose of this study is to detect antigen parts of M. mycetomatis, which act specifically with M. mycetomatis antibodies. METHODS: Cytoplasmic antigen was prepared from molecularly identified cultures of M. mycetomatis by sonication, ultracentrifugation, dried, weighed and appropriately reconstituted. M. mycetomatis cytoplasmic antigen were separated using 12% sodium dodecyl sulfate polyacrylamide gel, and immunoblotting to detect the reactive ones.Immunoblotting was carried out in nitrocellulose strips containing different molecular size. Sera from patients and co-patients as control were used. RESULTS: When stained with Coomassie brilliant blue R 250 seven molecular weights appeared but only three, 45, 60, 95 kDa reacted with M. mycetomatis patients few from control group, one from a malaria patient. No reactive band was observed with sera from actinomycetoma, Aspergillus flavus-associated aspergillosis, schistosomiasis, leishmaniasis, fungal sinusitis nor healthy controls. CONCLUSIONS: Specific fractions of M. mycetomatis antigen which were demonstrated by immunoblotting showed 75% sensitivity and 95% specificity. The true negative tests were 14 patients (32.5%). This also means that immunoblotting is reasonably reliable in diagnosis and follow-up of eumycetoma patients. PMID- 27198218 TI - Distinct patterns of Cas9 mismatch tolerance in vitro and in vivo. AB - Cas9, a CRISPR-associated RNA-guided nuclease, has been rapidly adopted as a tool for biochemical and genetic manipulation of DNA. Although complexes between Cas9 and guide RNAs (gRNAs) offer remarkable specificity and versatility for genome manipulation, mis-targeted events occur. To extend the understanding of gRNA::target homology requirements, we compared mutational tolerance for a set of Cas9::gRNA complexes in vitro and in vivo (in Saccharomyces cerevisiae). A variety of gRNAs were tested with variant libraries based on four different targets (with varying GC content and sequence features). In each case, we challenged a mixture of matched and mismatched targets, evaluating cleavage activity on a wide variety of potential target sequences in parallel through high throughput sequencing of the products retained after cleavage. These experiments evidenced notable and consistent differences between in vitro and S. cerevisiae (in vivo) Cas9 cleavage specificity profiles including (i) a greater tolerance for mismatches in vitro and (ii) a greater specificity increase in vivo with truncation of the gRNA homology regions. PMID- 27198219 TI - The RING 2.0 web server for high quality residue interaction networks. AB - Residue interaction networks (RINs) are an alternative way of representing protein structures where nodes are residues and arcs physico-chemical interactions. RINs have been extensively and successfully used for analysing mutation effects, protein folding, domain-domain communication and catalytic activity. Here we present RING 2.0, a new version of the RING software for the identification of covalent and non-covalent bonds in protein structures, including pi-pi stacking and pi-cation interactions. RING 2.0 is extremely fast and generates both intra and inter-chain interactions including solvent and ligand atoms. The generated networks are very accurate and reliable thanks to a complex empirical re-parameterization of distance thresholds performed on the entire Protein Data Bank. By default, RING output is generated with optimal parameters but the web server provides an exhaustive interface to customize the calculation. The network can be visualized directly in the browser or in Cytoscape. Alternatively, the RING-Viz script for Pymol allows visualizing the interactions at atomic level in the structure. The web server and RING-Viz, together with an extensive help and tutorial, are available from URL: http://protein.bio.unipd.it/ring. PMID- 27198220 TI - BindUP: a web server for non-homology-based prediction of DNA and RNA binding proteins. AB - Gene expression is a multi-step process involving many layers of regulation. The main regulators of the pathway are DNA and RNA binding proteins. While over the years, a large number of DNA and RNA binding proteins have been identified and extensively studied, it is still expected that many other proteins, some with yet another known function, are awaiting to be discovered. Here we present a new web server, BindUP, freely accessible through the website http://bindup.technion.ac.il/, for predicting DNA and RNA binding proteins using a non-homology-based approach. Our method is based on the electrostatic features of the protein surface and other general properties of the protein. BindUP predicts nucleic acid binding function given the proteins three-dimensional structure or a structural model. Additionally, BindUP provides information on the largest electrostatic surface patches, visualized on the server. The server was tested on several datasets of DNA and RNA binding proteins, including proteins which do not possess DNA or RNA binding domains and have no similarity to known nucleic acid binding proteins, achieving very high accuracy. BindUP is applicable in either single or batch modes and can be applied for testing hundreds of proteins simultaneously in a highly efficient manner. PMID- 27198221 TI - spongeScan: A web for detecting microRNA binding elements in lncRNA sequences. AB - Non-coding RNA transcripts such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are important genetic regulators. However, the functions of many of these transcripts are still not clearly understood. Recently, it has become apparent that there is significant crosstalk between miRNAs and lncRNAs and that this creates competition for binding between the miRNA, a lncRNA and other regulatory targets. Indeed, various competitive endogenous RNAs (ceRNAs) have already been identified where a lncRNA acts by sequestering miRNAs. This implies the down-regulation in the interaction of the miRNAs with their mRNA targets, what has been called a sponge effect. Multiple approaches exist for the prediction of miRNA targets in mRNAs. However, few methods exist for the prediction of miRNA response elements (MREs) in lncRNAs acting as ceRNAs (sponges). Here, we present spongeScan (http://spongescan.rc.ufl.edu), a graphical web tool to compute and visualize putative MREs in lncRNAs, along with different measures to assess their likely behavior as ceRNAs. PMID- 27198222 TI - Structure-Specific nuclease activities of Artemis and the Artemis: DNA-PKcs complex. AB - Artemis is a vertebrate nuclease with both endo- and exonuclease activities that acts on a wide range of nucleic acid substrates. It is the main nuclease in the non-homologous DNA end-joining pathway (NHEJ). Not only is Artemis important for the repair of DNA double-strand breaks (DSBs) in NHEJ, it is essential in opening the DNA hairpin intermediates that are formed during V(D)J recombination. Thus, humans with Artemis deficiencies do not have T- or B-lymphocytes and are diagnosed with severe combined immunodeficiency (SCID). While Artemis is the only vertebrate nuclease capable of opening DNA hairpins, it has also been found to act on other DNA substrates that share common structural features. Here, we discuss the key structural features that all Artemis DNA substrates have in common, thus providing a basis for understanding how this structure-specific nuclease recognizes its DNA targets. PMID- 27198224 TI - Skeletal muscle fiber analysis by atmospheric pressure scanning microprobe matrix assisted laser desorption/ionization mass spectrometric imaging at high mass and high spatial resolution. AB - Skeletal muscles are composed of heterogeneous muscle fibers with various fiber types. These fibers can be classified into different classes based on their different characteristics. MALDI mass spectrometric imaging (MSI) has been applied to study and visualize different metabolomics profiles of different fiber types. Here, skeletal muscles were analyzed by atmospheric pressure scanning microprobe MALDI-MSI at high spatial and high mass resolution. PMID- 27198223 TI - PKCalpha and HMGB1 antagonistically control hydrogen peroxide-induced poly-ADP ribose formation. AB - Harmful oxidation of proteins, lipids and nucleic acids is observed when reactive oxygen species (ROS) are produced excessively and/or the antioxidant capacity is reduced, causing 'oxidative stress'. Nuclear poly-ADP-ribose (PAR) formation is thought to be induced in response to oxidative DNA damage and to promote cell death under sustained oxidative stress conditions. However, what exactly triggers PAR induction in response to oxidative stress is incompletely understood. Using reverse phase protein array (RPPA) and in-depth analysis of key stress signaling components, we observed that PAR formation induced by H2O2 was mediated by the PLC/IP3R/Ca(2+)/PKCalpha signaling axis. Mechanistically, H2O2-induced PAR formation correlated with Ca(2+)-dependent DNA damage, which, however, was PKCalpha-independent. In contrast, PAR formation was completely lost upon knockdown of PKCalpha, suggesting that DNA damage alone was not sufficient for inducing PAR formation, but required a PKCalpha-dependent process. Intriguingly, the loss of PAR formation observed upon PKCalpha depletion was overcome when the chromatin structure-modifying protein HMGB1 was co-depleted with PKCalpha, suggesting that activation and nuclear translocation of PKCalpha releases the inhibitory effect of HMGB1 on PAR formation. Together, these results identify PKCalpha and HMGB1 as important co-regulators involved in H2O2-induced PAR formation, a finding that may have important relevance for oxidative stress associated pathophysiological conditions. PMID- 27198225 TI - Physiological restraint of Bak by Bcl-xL is essential for cell survival. AB - Due to the myriad interactions between prosurvival and proapoptotic members of the Bcl-2 family of proteins, establishing the mechanisms that regulate the intrinsic apoptotic pathway has proven challenging. Mechanistic insights have primarily been gleaned from in vitro studies because genetic approaches in mammals that produce unambiguous data are difficult to design. Here we describe a mutation in mouse and human Bak that specifically disrupts its interaction with the prosurvival protein Bcl-xL Substitution of Glu75 in mBak (hBAK Q77) for leucine does not affect the three-dimensional structure of Bak or killing activity but reduces its affinity for Bcl-xL via loss of a single hydrogen bond. Using this mutant, we investigated the requirement for physical restraint of Bak by Bcl-xL in apoptotic regulation. In vitro, Bak(Q75L) cells were significantly more sensitive to various apoptotic stimuli. In vivo, loss of Bcl-xL binding to Bak led to significant defects in T-cell and blood platelet survival. Thus, we provide the first definitive in vivo evidence that prosurvival proteins maintain cellular viability by interacting with and inhibiting Bak. PMID- 27198226 TI - A role for HOX13 proteins in the regulatory switch between TADs at the HoxD locus. AB - During vertebrate limb development, Hoxd genes are regulated following a bimodal strategy involving two topologically associating domains (TADs) located on either side of the gene cluster. These regulatory landscapes alternatively control different subsets of Hoxd targets, first into the arm and subsequently into the digits. We studied the transition between these two global regulations, a switch that correlates with the positioning of the wrist, which articulates these two main limb segments. We show that the HOX13 proteins themselves help switch off the telomeric TAD, likely through a global repressive mechanism. At the same time, they directly interact with distal enhancers to sustain the activity of the centromeric TAD, thus explaining both the sequential and exclusive operating processes of these two regulatory domains. We propose a model in which the activation of Hox13 gene expression in distal limb cells both interrupts the proximal Hox gene regulation and re-enforces the distal regulation. In the absence of HOX13 proteins, a proximal limb structure grows without any sign of wrist articulation, likely related to an ancestral fish-like condition. PMID- 27198227 TI - HuR and GRSF1 modulate the nuclear export and mitochondrial localization of the lncRNA RMRP. AB - Some mitochondrial long noncoding RNAs (lncRNAs) are encoded by nuclear DNA, but the mechanisms that mediate their transport to mitochondria are poorly characterized. Using affinity RNA pull-down followed by mass spectrometry analysis, we found two RNA-binding proteins (RBPs), HuR (human antigen R) and GRSF1 (G-rich RNA sequence-binding factor 1), that associated with the nuclear DNA-encoded lncRNA RMRP and mobilized it to mitochondria. In cultured human cells, HuR bound RMRP in the nucleus and mediated its CRM1 (chromosome region maintenance 1)-dependent export to the cytosol. After RMRP was imported into mitochondria, GRSF1 bound RMRP and increased its abundance in the matrix. Loss of GRSF1 lowered the mitochondrial levels of RMRP, in turn suppressing oxygen consumption rates and modestly reducing mitochondrial DNA replication priming. Our findings indicate that RBPs HuR and GRSF1 govern the cytoplasmic and mitochondrial localization of the lncRNA RMRP, which is encoded by nuclear DNA but has key functions in mitochondria. PMID- 27198229 TI - The Enok acetyltransferase complex interacts with Elg1 and negatively regulates PCNA unloading to promote the G1/S transition. AB - KAT6 histone acetyltransferases (HATs) are highly conserved in eukaryotes and are involved in cell cycle regulation. However, information regarding their roles in regulating cell cycle progression is limited. Here, we report the identification of subunits of the Drosophila Enok complex and demonstrate that all subunits are important for its HAT activity. We further report a novel interaction between the Enok complex and the Elg1 proliferating cell nuclear antigen (PCNA)-unloader complex. Depletion of Enok in S2 cells resulted in a G1/S cell cycle block, and this block can be partially relieved by depleting Elg1. Furthermore, depletion of Enok reduced the chromatin-bound levels of PCNA in both S2 cells and early embryos, suggesting that the Enok complex may interact with the Elg1 complex and down-regulate its PCNA-unloading function to promote the G1/S transition. Supporting this hypothesis, depletion of Enok also partially rescued the endoreplication defects in Elg1-depleted nurse cells. Taken together, our study provides novel insights into the roles of KAT6 HATs in cell cycle regulation through modulating PCNA levels on chromatin. PMID- 27198228 TI - Histone H3K4 methylation regulates deactivation of the spindle assembly checkpoint through direct binding of Mad2. AB - Histone H3 methylation on Lys4 (H3K4me) is associated with active gene transcription in all eukaryotes. In Saccharomyces cerevisiae, Set1 is the sole lysine methyltransferase required for mono-, di-, and trimethylation of this site. Although H3K4me3 is linked to gene expression, whether H3K4 methylation regulates other cellular processes, such as mitosis, is less clear. Here we show that both Set1 and H3K4 mutants display a benomyl resistance phenotype that requires components of the spindle assembly checkpoint (SAC), including Bub3 and Mad2. These proteins inhibit Cdc20, an activator of the anaphase-promoting complex/cyclosome (APC/C). Mutations in Cdc20 that block Mad2 interactions suppress the benomyl resistance of both set1 and H3K4 mutant cells. Furthermore, the HORMA domain in Mad2 directly binds H3, identifying a new histone H3 "reader" motif. Mad2 undergoes a conformational change important for execution of the SAC. We found that the closed (active) conformation of both yeast and human Mad2 is capable of binding methylated H3K4, but, in contrast, the open (inactive) Mad2 conformation limits interaction with methylated H3. Collectively, our data indicate that interactions between Mad2 and H3K4 regulate resolution of the SAC by limiting closed Mad2 availability for Cdc20 inhibition. PMID- 27198231 TI - Alien Parasites May Survive Even if Their Original Hosts Do Not. PMID- 27198230 TI - Evolution of a transcriptional regulator from a transmembrane nucleoporin. AB - Nuclear pore complexes (NPCs) emerged as nuclear transport channels in eukaryotic cells ~1.5 billion years ago. While the primary role of NPCs is to regulate nucleo-cytoplasmic transport, recent research suggests that certain NPC proteins have additionally acquired the role of affecting gene expression at the nuclear periphery and in the nucleoplasm in metazoans. Here we identify a widely expressed variant of the transmembrane nucleoporin (Nup) Pom121 (named sPom121, for "soluble Pom121") that arose by genomic rearrangement before the divergence of hominoids. sPom121 lacks the nuclear membrane-anchoring domain and thus does not localize to the NPC. Instead, sPom121 colocalizes and interacts with nucleoplasmic Nup98, a previously identified transcriptional regulator, at gene promoters to control transcription of its target genes in human cells. Interestingly, sPom121 transcripts appear independently in several mammalian species, suggesting convergent innovation of Nup-mediated transcription regulation during mammalian evolution. Our findings implicate alternate transcription initiation as a mechanism to increase the functional diversity of NPC components. PMID- 27198232 TI - Antimicrobial Consumption in Medicated Feeds in Vietnamese Pig and Poultry Production. AB - Antimicrobials are extensively used as growth promoters in animal feeds worldwide, but reliable estimates are lacking. We conducted an internet-based survey of commercial chicken and pig feed products officially approved for sale in Vietnam over the period March-June 2015. Information on the antimicrobial contents in feed products, alongside animal production data, was used to estimate in-feed antimicrobial consumption to produce one kilogram of live animal (chicken, pig), as well as to estimate country-wide antimicrobial consumption through animal feeds. A total of 1462 commercial feed formulations were examined. The survey-adjusted estimated antimicrobial contents were 25.7 and 62.3 mg/kg in chicken and pig feeds, respectively. Overall, it was estimated that 77.4 mg [95% CI 48.1-106.8] and 286.6 mg [95% CI 191.6-418.3] of in-feed antimicrobials were used to raise 1 kg of live chicken and pig, respectively. Bacitracin (15.5% feeds), chlortetracycline (11.4%), and enramycin (10.8%) were the most common antimicrobials present in chicken feed formulations, whereas bacitracin (24.8%), chlortetracycline (23.9%), and florfenicol (17.4%) were the most common in pig feed formulations. Overall, 57% of the total quantitative usage consisted of antimicrobials regarded by WHO of importance for human medicine, including amoxicillin, colistin, tetracyclines, neomycin, lincomycin, and bacitracin. These figures confirm a very high magnitude of in-feed consumption of antimicrobials, especially in pig production. Results from this study should encourage further monitoring of antimicrobials used in animal production, and foster discussion about existing policies on inclusion of antimicrobials in animal feed rations. PMID- 27198233 TI - Effect of concomitant vitamin D deficiency or insufficiency on lumbar spine volumetric bone mineral density and trabecular bone score in primary hyperparathyroidism. AB - Lower vitamin D and higher parathyroid hormone (PTH) levels are associated with higher volumetric BMD and bone strength at the lumbar spine as measured by central quantitative computed tomography in primary hyperparathyroidism (PHPT), but there are no differences in bone microarchitecture as measured by trabecular bone score (TBS). INTRODUCTION: The purpose of this study was to evaluate the association between 25-hydroxyvitamin D (25OHD) and volumetric bone mineral density (vBMD) and the TBS at the lumbar spine (LS) in PHPT. METHODS: This is a cross-sectional analysis of PHPT patients with and without low 25OHD. We measured vBMD with quantitative computed tomography (cQCT) and TBS by dual-energy X-ray absorptiometry (DXA) at the LS in 52 and 88 participants, respectively. RESULTS: In the cQCT cohort, those with lower vitamin D (<20 vs. 20-29 vs. >=30 ng/ml) tended to be younger (p = 0.05), were less likely to use vitamin D supplementation (p < 0.01), and had better renal function (p = 0.03). Those with 25OHD <20 ng/ml had 80 and 126 % higher serum PTH levels respectively vs. those with 25OHD 20-29 ng/ml (p = 0.002) and 25OHD >=30 ng/ml (p < 0.0001). Covariate adjusted integral and trabecular vBMD were higher in those with 25OHD 20-29 vs. those with 25OHD >=30 ng/ml, but those with 25OHD <20 did not differ. Because there were few participants with 25OHD deficiency, we also compared those with vitamin D <30 vs. >=30 ng/ml. Covariate-adjusted integral and trabecular vBMD were 23 and 30 % higher respectively (both p < 0.05) in those with vitamin D <30 vs. >=30 ng/ml. TBS was in the partially degraded range but did not differ by vitamin D status. CONCLUSION: In mild PHPT, lower 25OHD is associated with higher PTH, but vitamin D deficiency and insufficiency using current clinical thresholds did not adversely affect lumbar spine skeletal health in PHPT. Further work is needed to determine if higher vBMD in those with lower vitamin D is due to an anabolic effect of PTH. PMID- 27198234 TI - Dietary patterns are associated with bone mineral density in an urban Mexican adult population. AB - Several types of nutrients and foods affect bone mineral density (BMD). However, these nutrients occur together in food groups and dietary patterns, and the overall effects of dietary patterns are not yet well known. INTRODUCTION: We evaluated the associations between dietary patterns and BMD among adults participating in the Health Workers Cohort Study. METHODS: In a cross-sectional analysis, we examined 6915 Mexican adults aged 20-80 years. All participants completed a validated self-administered food frequency questionnaire (FFQ) and had total, hip, and spine BMD measurements assessed by dual-energy X-ray absorptiometry (DXA). The FFQ included 116 foods, which were grouped into 22 categories and entered into a factor analysis to derive dietary patterns. RESULTS: Three dietary patterns emerged-a Prudent, a Refined foods, and a Dairy and fish pattern. After adjustment for potential confounders, those in the highest quintile of the Prudent pattern had lower odds (OR) of low spine BMD (OR = 0.80; 95 % CI 0.68, 0.94; P for trend = 0.031) compared to those in the lowest quintile. In contrast, participants in the highest quintile of the Refined foods pattern had greater odds of low total BMD (OR = 1.74; 95 % CI 1.10, 2.76; P for trend = 0.016) than those in the lowest quintile. Finally, participants in the highest quintile of the Dairy and fish dietary pattern had significantly lower likelihood of having low BMD. CONCLUSION: This study identified specific dietary patterns associated with BMD among a Mexican adult population and highlights the importance of promoting food-based prevention strategies for maintaining bone health. PMID- 27198235 TI - Internet-based incentives increase blood glucose testing with a non-adherent, diverse sample of teens with type 1 diabetes mellitus: a randomized controlled Trial. AB - Non-adherence with self-monitoring blood glucose (SMBG) among teenagers with type 1 diabetes can be a problem. The purpose of this study was to investigate the feasibility, acceptability, and preliminary efficacy of using Internet-based incentives to improve adherence with SMBG in non-adherent teenagers. Participants were randomly assigned to contingent (CS; N = 23), where they had to meet web camera-verified SMBG goals to earn incentives, or non-contingent (NS) groups (N = 18), where they earned incentives independent of adherence. Brief motivational interviewing (MI) was given prior to the intervention. Attrition was 15 % in the CS group. Participants and parents endorsed the intervention on all intervention dimensions. Daily SMBG increased after one MI session, and further increased when incentives were added, but significantly more for so for older participants. SMBG declined slowly over time, but only returned to baseline levels for younger NS participants. Internet-based incentive interventions are feasible, acceptable, and show promise for improving adherence with SMBG. PMID- 27198236 TI - Monitoring live human mesenchymal stromal cell differentiation and subsequent selection using fluorescent RNA-based probes. AB - Investigating mesenchymal stromal cell differentiation requires time and multiple samples due to destructive endpoint assays. Osteogenesis of human bone marrow derived mesenchymal stromal cells (hBMSCs) has been widely studied for bone tissue engineering. Recent studies show that the osteogenic differentiation of hBMSCs can be assessed by quantifying the ratio of two important transcription factors (Runx2/Sox9). We demonstrate a method to observe mRNA expression of two genes in individual live cells using fluorescent probes specific for Runx2 and Sox9 mRNA. The changes of mRNA expression in cells can be observed in a non destructive manner. In addition, the osteogenic hBMSCs can be prospectively identified and obtained based on the relative intracellular fluorescence of Sox9 in relation to Runx2 using fluorescence activated cell sorting. Relatively homogeneous cell populations with high osteogenic potential can be isolated from the original heterogeneous osteogenically induced hBMSCs within the first week of induction. This offers a more detailed analysis of the effectiveness of new therapeutics both at the individual cell level and the response of the population as a whole. By identifying and isolating differentiating cells at early time points, prospective analysis of differentiation is also possible, which will lead to a greater understanding of MSC differentiation. PMID- 27198237 TI - What Political Framework Is Necessary to Reduce Malnutrition? A Civil Society Perspective. AB - Around 800 million people worldwide are still starving. Around 2 billion are somehow able to allay their hunger yet remain malnourished because their food does not contain sufficient nutrients. There are many reasons for this: for people living in poverty and precarious conditions, the priority is to fill their stomach, and the quality of food seems less important. Since the 1960s, global food production has been focused on increasing yield, not food quality. Mass produced convenience food with high fat and carbohydrate contents but containing few nutrients is on the rise and - as a result of price wars - often replaces healthier locally grown products. To overcome global hunger and malnutrition, civil society organizations urge governments to turn towards sustainable and human rights-based development, including sustainable agricultural and fishing policies, to contribute to the eradication of poverty. This development is first and foremost guided by the right to food. In a policy that enables farmers to produce enough food that is healthy and rich in nutrients, the following principles should be fulfilled. Governments should assume responsibility for the international impacts of their agricultural policy decisions. The food sovereignty of other countries should be respected. Policies should enable self supply of the population with healthy food and should promote the protection of resources, the climate, biodiversity and animal welfare. Strengthening rural structures, local economies, labor rights and small-scale food producers, establishing public programs that provide locally produced food, applying stringent standards for food labeling and the regulation of unhealthy products and paying special attention to the first 1,000 days of life as the starting point of a good and healthy well-being are core elements of such a political framework. PMID- 27198239 TI - Thrombin Stimulated Platelet-Derived Exosomes Inhibit Platelet-Derived Growth Factor Receptor-Beta Expression in Vascular Smooth Muscle Cells. AB - BACKGROUND/AIMS: It is difficult to predict acute thrombotic cardiovascular events in the clinic. Few studies have reported the presence of plasma exosomes containing microRNAs (miRNAs) in cardiovascular events. Therefore, we aimed to investigate the levels of miR-223, miR-339 and miR-21 in plasma exosomes before thrombosis in mouse models of carotid tandem stenosis, as well as the mechanisms underlying the origin and function of these exosomal miRNAs. METHODS: Plasma samples were collected from the carotid tandem stenosis and sham control groups of our successfully developed atherothrombosis mouse models before thrombosis. Platelets from healthy volunteers and mice were purified to obtain thrombin stimulated platelet-derived exosomes. Exosomes were isolated via differential ultracentrifugation, and western blotting and transmission electron microscopy were used for their identification. The total RNA was extracted, and quantitative real-time PCR was performed to determine the expression levels of miR-223, miR 339 and miR-21. DAVID Tools were used to analyze the pathways that were enriched among the miRNA target genes. Immuno-fluorescence staining was performed to identify the protein expression levels of platelet-derived exosome target genes in vascular smooth muscle cells (SMCs) in vitro and in vivo. RESULTS: The levels of miR-223, miR-339 and miR-21, which are associated with platelet activation, were elevated in pooled mouse plasma exosomes before thrombosis and enriched in thrombin-stimulated platelet-derived exosomes in vitro. Platelet-derived growth factor receptor-beta (PDGFRbeta) was a target of these miRNAs, and PDGFRbeta expression in vascular smooth muscle cells (SMCs) was inhibited following incubation with platelet-derived exosomes. Platelet-derived exosomes could also inhibit PDGF-stimulated SMC proliferation. Furthermore, a decrease in PDGFRbeta expression was observed in vascular SMCs around thrombotic areas in vivo. CONCLUSIONS: Our data indicate that activated platelet-derived exosomes containing miR-223, miR-339 and miR-21 could be transferred into SMCs and inhibit PDGFRbeta expression; these exosomal miRNAs may be a biomarker for predicting atherothrombosis. PMID- 27198238 TI - Preoperative Endoscopy Prior to Bariatric Surgery: a Systematic Review and Meta Analysis of the Literature. AB - BACKGROUND: There is debate regarding preoperative endoscopy (EGD) in patients undergoing bariatric surgery. Some centers perform EGD routinely in all patients; others perform EGD selectively. The objective of this study was to perform a systematic review and meta-analysis of the existing literature to estimate how frequently preoperative EGD changes management. METHODS: Our review yielded 28 studies encompassing 6616 patients. Baseline characteristics including age and body mass index (BMI) were included. Patients were grouped based on EGD findings into two groups: Group 1-findings which did not significantly change management (e.g., mild/moderate duodenitis, Grade A/B esophagitis, mild/moderate gastritis, H. pylori infection, hiatal hernia <2 cm); Group 2-findings which delayed, altered, or cancelled surgery (e.g., severe duodenitis, Grade C/D esophagitis, gastric varices, hiatal hernia >2 cm, mass/carcinoma). A general estimating equation (GEE) model accounting for the correlated data within each study was used to calculate confidence intervals around the estimate of how frequently surgery was delayed or altered. RESULTS: Mean age was 41.4 +/- 2.9 years, the majority was women, and mean preoperative BMI was 47 +/- 3.2 kg/m2. Overall 92.4 % (n = 6112) had a normal EGD or findings that did not change clinical management and 7.6 % (n = 504); 95 % CI [4.6, 12.4 %] had findings that delayed/altered surgery. The revised estimate was 20.6 %; 95%CI [14.5, 28.2 %] if all esophagitis (regardless of grade) were categorized into Group 2. The approximate incidence of Barrett's esophagus and carcinoma were 0.1 and 0.08 %, respectively. CONCLUSION: A selective approach to preoperative EGD may be considered, based on the patients' symptoms, risk factors, and type of procedure planned. PMID- 27198455 TI - Herpes simplex virus type 2: Cluster of unrelated cases in an intensive care unit. AB - Herpes simplex viruses, which are associated with various clinical manifestations, can be transmitted to critically ill patients from other patients or health care staff. We report an apparent outbreak of mucocutaneous herpes simplex virus 2 infections (5 cases in 10 weeks). An epidemiologic investigation and genotype analysis showed no connections among the 5 cases. PMID- 27198457 TI - Another Piece of the Puzzle of Podocyte B7-1 Expression: Lupus Nephritis. AB - BACKGROUND/AIMS: Lupus nephritis (LN) is a frequent complication and a major predictor of poor prognosis of systemic lupus erythematosus. Immune complex deposition and T cell infiltration are crucial events in LN pathogenesis. B7-1 (CD80), normally expressed by antigen-presenting cells, is one of the major co stimulators of T-cell activation through the binding with its counter-receptors CD28 and cytotoxic T-lymphocyte antigen-4. Unexpectedly, B7-1 induction was described at the podocyte level in patients affected by different renal diseases, including LN. These observations suggested a novel exciting function for B7-1 as a biomarker of podocyte injury, and hence that B7-1 inhibitory drugs could serve as podocyte-targeted treatment of intractable renal diseases. However, subsequent studies hardly questioned the reliability of B7-1 detection assays and the therapeutic efficacy of B7-1 blockade in proteinuric patients, casting doubts on B7-1 expression by podocytes. Here, we thoroughly investigated whether B7-1 was indeed expressed by podocytes in LN, before even considering employing B7-1 blockade in patients with severe manifestations of LN and unfavourable prognosis. METHODS: Applying different immunohistochemical assays with 4 primary antibodies, we analysed kidney biopsies from 42 LN patients at different stages of the disease, and from NZB/NZW mice, an LN model. RESULTS: B7-1 was not induced in podocytes in human and murine LN; instead its expression was confined to infiltrating inflammatory cells. CONCLUSION: B7-1 is not expressed by podocytes in LN. A renoprotective effect of B7-1 blockade in LN patients cannot be ruled out but, if confirmed, cannot be the result of an effect on podocyte B7-1. PMID- 27198456 TI - Cystatin C Based Equation Accurately Estimates Glomerular Filtration Rate in Children With Solid and Central Nervous System Tumours: Enough Evidence to Change Practice? AB - BACKGROUND: Assessing the glomerular filtration rate (GFR) of paediatric patients receiving nephrotoxic chemotherapy is a vital element of clinical practice. Isotopically measured GFR is the gold standard in terms of accuracy but requires injection of tracer followed by several hours of blood tests. Estimation of GFR using creatinine is widely used but inaccurate, and there is increasing concern regarding its usage for paediatric oncology patients. Cystatin C (CysC) based equations are increasingly used in other paediatric specialities to estimate GFR, and their usefulness in paediatric oncology practice is becoming evident. METHODS: We assessed the renal function of children with solid tumours and CNS tumours receiving nephrotoxic chemotherapy over a 1-year period using paired CysC and isotopic GFR. RESULTS: Fifty-six sets of measurements were reviewed with estimated GFR predicted using CysC-based and creatinine-based equations. The best performing equation was the 'new CKiD' equation, which estimated GFR within 30% of the measured GFR on 86% of occasions, outperforming the Schwartz equation. If estimated GFR using this equation was >100 ml/min/1.73 m(2) , all values of measured GFR were normal at >90 ml/min/1.73 m(2) , a category containing two thirds of all measurements. CONCLUSIONS: The new CKiD equation predicts GFR in paediatric oncology patients with more accuracy than creatinine-based equations. When the estimated GFR is >100 ml/min/1.73 m(2) , isotopic GFR can be safely omitted. PMID- 27198458 TI - Psychoanalysis and bioethics: a Lacanian approach to bioethical discourse. AB - This article aims to develop a Lacanian approach to bioethics. Point of departure is the fact that both psychoanalysis and bioethics are practices of language, combining diagnostics with therapy. Subsequently, I will point out how Lacanian linguistics may help us to elucidate the dynamics of both psychoanalytical and bioethical discourse, using the movie One flew over the Cuckoo's Nest and Sophocles' tragedy Antigone as key examples. Next, I will explain the 'topology' of the bioethical landscape with the help of Lacan's three dimensions: the imaginary, the symbolical and the real. This will culminate in an assessment of the dynamics of bioethical discourse with the help of Lacan's theorem of the four discourses. Bioethics, I will argue, is not a homogeneous discourse. Rather, four modalities of bioethical discourse can be distinguished, all of them displaying specific weaknesses and strengths, opportunities and threats. This will be elucidated with the help of two case studies, namely the debates on human reproductive technologies and on the use of animals as biomedical research models. PMID- 27198459 TI - Coordinated path following of multiple underacutated marine surface vehicles along one curve. AB - This paper investigates the coordinated path following problem for a fleet of underactuated marine surface vehicles (MSVs) along one curve. The dedicated control design is divided into two tasks. One is to steer individual underactuated MSV to track the given spatial path, and the other is to force the vehicles dispersed on a parameterized path subject to the constraints of a communication network. Specifically, a robust individual path following controller is developed based on a line-of-sight (LOS) guidance law and a reduced order extended state observer (ESO). The vehicle sideslip angle due to environmental disturbances can be exactly identified. Then, the vehicle coordination is achieved by a path variable containment approach, under which the path variables are evenly dispersed between two virtual leaders. Another reduced order ESO is developed to identify the composite disturbance related to the speed of virtual leaders and neighboring vehicles. The proposed coordination design is distributed since the reference speed does not need to be known by all vehicles as a priori. The input-to-state stability of the closed-loop network system is established via cascade theory. Simulation results demonstrate the effectiveness of the proposed design method. PMID- 27198460 TI - Automatic optic disc localization and segmentation in retinal images by a line operator and level sets. AB - BACKGROUND: Existing methods may fail to locate and segment the optic disc (OD) due to imprecise boundaries, inconsistent image contrast and deceptive edge features in retinal images. OBJECTIVE: To locate the OD and detect the OD boundary accurately. METHODS: The method exploits a multi-stage strategy in the detection procedure. Firstly, OD location candidate regions are identified based on high-intensity feature and vessels convergence property. Secondly, a line operator filter for circular brightness feature detection is designed to locate the OD accurately on candidates. Thirdly, an initialized contour is obtained by iterative thresholding and ellipse fitting based on the detected OD position. Finally, a region-based active contour model in a variational level set formulation and ellipse fitting are employed to estimate the OD boundary. RESULTS: The proposed methodology achieves an accuracy of 98.67% for OD identification and a mean distance to the closest point of 2 pixels in detecting the OD boundary. CONCLUSION: The results illuminate that the proposed method is effective in the fast, automatic, and accurate localization and boundary detection of the OD. The present work contributes to the more effective evaluation of the OD and realizing automatic screening system for early eye diseases to a large extent. PMID- 27198461 TI - How to prevent the infection of contaminated abdominal incisions. AB - BACKGROUND: Surgical site infection is one of the most common complications of conventional laparoscopic surgery. Preventing infection of the incision is particularly important. OBJECTIVE: To discuss how to prevent the occurrence of surgical site infection after contaminated abdominal surgery. METHODS: Five hundred and fifty-one surgery patients with ''contaminated abdominal incisions'' from January 2011 to May 2013 were analyzed in terms of the preventative treatment, and summarized for surgical site infection. Subcutaneous tissue flushed with normal saline + hydrogen peroxide before suturing in the intervention 1 group; subcutaneous tissue flushed with normal saline + 0.5% povidone-iodine before suturing in the intervention 2 group. RESULTS: When subcutaneous fat was contaminated to a depth of <= 2.5 cm, the rates of surgical site infection in the control group and the intervention groups showed no significant difference (P > 0.05). When subcutaneous fat was contaminated to a depth of >= 3.0 cm, the rate of surgical site infection in the control group compared with the intervention one group was not statistically different (P > 0.05). The rate of surgical site infection in the control group compared with the intervention two group was statistical significant (P < 0.05). The rate of surgical site infection in the intervention one group compared with the intervention two group was statistical significant (P < 0.05). CONCLUSIONS: Preoperative control of the blood sugar; correction of anemia and the hypoalbuminemia; use of intraoperative the high-frequency electrotome; irrigation of the incision with plenty of physiological saline +$ iodophor before suturing the subcutaneous fat layer were key to effectively preventing infection in contaminated abdominal incisions. PMID- 27198462 TI - A three-dimensional model and numerical simulation regarding thermoseed mediated magnetic induction therapy conformal hyperthermia. AB - In order to ensure the safety and effectiveness of magnetic induction hyperthermia in clinical applications, numerical simulations on the temperature distributions and extent of thermal damage to the targeted regions must be conducted in the preoperative treatment planning system. In this paper, three models, including a thermoseed thermogenesis model, tissue heat transfer model, and tissue thermal damage model, were established based on the four-dimensional energy field, temperature field, and thermal damage field distributions exhibited during hyperthermia. In addition, a numerical simulation study was conducted using the Finite Volume Method (FVM), and the accuracy and reliability of the magnetic induction hyperthermia model and its numerical calculations were verified using computer simulations and experimental results. Thus, this study promoted the application of computing methods to magnetic induction therapy and conformal hyperthermia, and improved the accuracy of the temperature field and tissue thermal damage distribution predictions. PMID- 27198464 TI - UV laser photoactivation of hexachloroplatinate bound to individual nucleobases in vacuo as molecular level probes of a model photopharmaceutical. AB - Isolated molecular clusters of adenine, cytosine, thymine and uracil bound to hexachloroplatinate, PtCl6(2-), have been studied using laser electronic photodissociation spectroscopy to investigate photoactivation of a platinum complex in the vicinity of a nucleobase. These metal complex-nucleobase clusters represent model systems for identifying the fundamental photochemical processes occurring in photodynamic platinum drug therapies that target DNA. This is the first study to explore the specific role of a strongly photoactive platinum compound in the aggregate complex. Each of the clusters studied displays a broadly similar absorption spectra, with a strong lambdamax ~ 4.6 eV absorption band and a subsequent increase in the absorption intensity towards higher spectral-energy. The absorption bands are traced to ligand-to-metal-charge transfer excitations on the PtCl6(2-) moiety within the cluster, and result in Cl(-).nucleobase and PtCl5(-) as primary photofragments. These results demonstrate how selective photoexcitation can drive distinctive photodecay channels for a model photo-pharmaceutical. In addition, cluster absorption due to excitation of nucleobase-centred chromophores is observed in the region around 5 eV. For the uracil cluster, photofragments consistent with ultrafast decay of the excited state and vibrational predissociation on the ground-state surface are observed. However, this decay channel becomes successively weaker on going from thymine to cytosine to adenine, due to differential coupling of the excited states to the electron detachment continuum. These effects demonstrate the distinctive photophysical characteristics of the different nucleobases, and are discussed in the context of the recently recorded photoelectron spectra of theses clusters. PMID- 27198463 TI - Which indicators for measuring the daily physical activity? An overview on the challenges and technology limits for Telehealth applications. AB - BACKGROUND: Obesity is one of the biggest drivers of preventable chronic diseases and healthcare costs in Worldwide. Different prevention activities are suggested. By monitoring daily energy expenditure (EE) could be possible make personalized diets and programming physical activity. In this, physical inactivity is one of the most important public health problems. Some studies refer the effort of the international community in promoting physical activities. Physical activity can be promoted only by increasing citizens' empowerment on taking care of their health, and it passes from the improving of individual information. Technology can offer solutions and metrics for monitoring and measuring daily activity by interacting with individuals, sharing information and feedbacks. OBJECTIVE: In this study we review indicators of total energy expenditure and weaknesses of available devices in assessing these parameters. METHODS: Literature review and technology testing EuNetHta core model. RESULTS: For the clinical aspects, it is fundamental to take into account all the factor that can influence the personal energy expenditure as: heart rate, blood pressure and thermoregulation (influenced by the body temperature). DISCUSSION: In this study we focused the attention on the importance of tools to encourage the physical activity. We made an analysis of the factor that can influence the right analysis of energy expenditure and at the same time the energy regime. A punctual monitoring of the exercise regime could be helpful in Telemedicine application as Telemonitorig. More study are needed to value the impact of physical activity tracker in Telemonitorig protocols. CONCLUSION: On the assessment of the energy expenditure, critical issues are related to the physiological data acquisition. Sensors connected with mobile devices could be important tools for disease prevention and interventions affecting health behaviors. New devices applications are potential useful for telemedicine assistance, but security of data and the related communication protocol limits should be taking into account. PMID- 27198465 TI - Nutrition Transition in Rural Tanzania and Kenya. AB - All three types of malnutrition - underweight, overweight and micronutrient deficiency - are experienced in countries undergoing a nutrition transition, and they can occur in parallel in one community or even one household. To combat this triple burden of malnutrition, a combination of different strategies will be necessary, including a focus on food-based strategies that promote the consumption of a wide range of foods across nutritionally distinct food groups. In addition to a literature review, data from our own nutrition studies in both Tanzania and Kenya are presented in this paper. The literature review revealed an average of 10% of children in urban areas of Kenya and Tanzania with overweight and obesity, which is an alarming trend, and it is suggested that interventions need to start not only at school but also with adolescent girls and pregnant women to target the '1,000-day window'. From own study data, dietary patterns were generated that included a 'purchase' pattern dominated by bought and processed foods, indicating a possible nutrition transition even in the rural areas of both countries. Vegetable and especially fruit consumption was low in both countries. In addition, in Kenya, study participants exceeded the suggested maximum level of sugar consumption per day, which will most likely contribute to increasing levels in overweight and obesity prevalence and other noncommunicable diseases in general. As sugar was mainly consumed in combination with black tea, next to eating habits, changing drinking habits is also an important part of the nutrition transition and needs to receive more attention. A 'healthy eating at school and at home strategy' is suggested, which needs the support of both schools and parents/caregivers. In general, to take countermeasures against the negative trends of nutrition transition, joint efforts from all players in the field - not only those in nutrition, health and medicine, but also those in education and agriculture - will be essential. PMID- 27198466 TI - Relationship between volume of the seminal vesicles and sexual activity in middle aged men. AB - The relationship between volume of the seminal vesicles and the frequency of sex and sexual function in middle-aged men is not clear. This study included 81 patients who were diagnosed with localized prostate cancer. Volume of the seminal vesicles was examined using a volume analyser from computed tomography. Sexual function was subjectively evaluated using the Expanded Prostate Cancer Index Composite and Erection Hardness Score. The frequency of sex was surveyed using our original questionnaire. The mean +/- SD age of the patients was 67.7 +/- 5.3 years. There was no relationship between the volume of seminal vesicles and age of the patients. Volume of the seminal vesicles in patients who answered that they had sexual activity at least once a year was significantly larger than in those who answered no sexual activity for several years (P < .01) Moreover, among sexually active, middle-aged men, volume of the seminal vesicles was significantly larger in those who had a sexual frequency once every 3 months than in those who had a sexual frequency once every 6 months or once a year (P < .05). Our study suggests that the volume of seminal vesicles of middle-aged men is correlated with sexual activity. PMID- 27198467 TI - Baboon vaginal microbial flora. AB - BACKGROUND: Knowledge of the composition of vaginal microbial ecosystem is essential for understanding the etiology, prevention, and treatment of vaginal diseases. A baboon model has been used to provide detailed understanding of reproductive physiology and immunology applicable to women. However, little is known about the composition of its vaginal microbial ecosystem. METHODS: Gram stain and Nugent scores were used for assessment of baboon vaginal microbial flora. Biochemical identification and analysis of isolates were performed using the api((r)) kits and identification software. RESULTS: Species of Lactobacilli, Staphylococci, Clostridia, Bacilli, Corynebacteria, Gram-negative rods, other Gram-positive rods, cocci and Candida, were isolated. Healthy vaginal microbiota consisted mainly of lactobacillus morphotypes. Animals with high Nugent scores had increased number of Gram-positive cocci and variable rods, with increased number of Gram-negative morphotypes. CONCLUSIONS: The baboon vaginal microbiota is heterogeneous in terms of species composition and is typified by a scarcity of lactobacilli. PMID- 27198468 TI - Synergistic Catalysis: Enantioselective Ring Expansion of Vinyl Cyclopropanes Combining Four Catalytic Cycles for the Synthesis of Highly Substituted Spirocyclopentanes Bearing up to Four Stereocenters. AB - A double synergistic cascade reaction is reported, combining transition metal and amine catalysis. The reaction between vinyl cyclopropanes and enals renders the final cyclopentane derivatives in excellent yields and stereoselectivities. PMID- 27198470 TI - Hospital pharmacy medication reconciliation practice in Jordan: perceptions and barriers. AB - RATIONALE, AIMS AND OBJECTIVES: The primary aim of this study is to gain an insight into hospital pharmacists' current practice and perceptions towards medicine reconciliation and to identify common challenges preventing pharmacists from providing this service. METHODS: A cross-sectional study was conducted over 2 months (September-October 2015) at four Jordanian hospitals accredited by the Joint International Commission. A total of 76 pharmacists were recruited. Each pharmacist completed a validated structured questionnaire evaluating (1) pharmacist's current practice of medication reconciliation, (2) pharmacist's perceptions towards practicing medication reconciliation and (3) pharmacist's perceived barriers towards implementing medication reconciliation. RESULTS: There was relatively low awareness of the presence of current medication reconciliation policy in the hospitals. The majority of recruited pharmacists believed that pharmacists must have an integral role in providing such services to patients. They were also willing and able to provide help and support to all healthcare providers regarding the appropriateness of prescribed medications. It was evident that the greater the practice of medication reconciliation services and the higher the educational level, the better the overall perception score (r = 0.416 and r = 0.366, respectively; P-value = 0.000 for both). 'Time constraint' was the primary barrier discouraging pharmacists from practicing such service. CONCLUSION: This study demonstrates a relatively low awareness of the concept and policy of medication reconciliation process among Jordanian pharmacists. This suggests that educational programs are urgently needed to increase pharmacists' role and responsibilities in implementing and practicing reconciliation services with expected positive impact on patient care. PMID- 27198469 TI - Regular long-term red blood cell transfusions for managing chronic chest complications in sickle cell disease. AB - BACKGROUND: Sickle cell disease is a genetic haemoglobin disorder, which can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Sickle cell disease is one of the most common severe monogenic disorders in the world, due to the inheritance of two abnormal haemoglobin (beta globin) genes. The two most common chronic chest complications due to sickle cell disease are pulmonary hypertension and chronic sickle lung disease. These complications can lead to morbidity (such as reduced exercise tolerance) and increased mortality.This is an update of a Cochrane review first published in 2011 and updated in 2014. OBJECTIVES: We wanted to determine whether trials involving people with sickle cell disease that compare regular long-term blood transfusion regimens with standard care, hydroxycarbamide (hydroxyurea) any other drug treatment show differences in the following: mortality associated with chronic chest complications; severity of established chronic chest complications; development and progression of chronic chest complications; serious adverse events. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register. Date of the last search: 25 April 2016.We also searched for randomised controlled trials in the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1, 26 January 2016), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950), and ongoing trial databases to 26 January 2016. SELECTION CRITERIA: We included randomised controlled trials of people of any age with one of four common sickle cell disease genotypes, i.e. Hb SS, Sbeta(0), SC, or Sbeta(+) that compared regular red blood cell transfusion regimens (either simple or exchange transfusions) to hydroxycarbamide, any other drug treatment, or to standard care that were aimed at reducing the development or progression of chronic chest complications (chronic sickle lung and pulmonary hypertension). DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: No studies matching the selection criteria were found. AUTHORS' CONCLUSIONS: There is a need for randomised controlled trials looking at the role of long-term transfusion therapy in pulmonary hypertension and chronic sickle lung disease. Due to the chronic nature of the conditions, such trials should aim to use a combination of objective and subjective measures to assess participants repeatedly before and after the intervention. PMID- 27198471 TI - From Sugars to Wheels: The Conversion of Ethanol to 1,3-Butadiene over Metal Promoted Magnesia-Silicate Catalysts. AB - 1,3-Butadiene (1,3-BD) is a high-value chemical intermediate used mainly as a monomer for the production of synthetic rubbers. The ability to source 1,3-BD from biomass is of considerable current interest because it offers the potential to reduce the life-cycle greenhouse gas (GHG) impact associated with 1,3-BD production from petroleum-derived naphtha. Herein, we report the development and investigation of a new catalyst and process for the one-step conversion of ethanol to 1,3-BD. The catalyst is prepared by the incipient impregnation of magnesium oxide onto a silica support followed by the deposition of Au nanoparticles by deposition-precipitation. The resulting Au/MgO-SiO2 catalyst exhibits a high activity and selectivity to 1,3-BD and low selectivities to diethyl ether, ethylene, and butenes. Detailed characterization of the catalyst shows that the desirable activity and selectivity of Au/MgO-SiO2 are a consequence of a critical balance between the acidic-basic sites associated with a magnesium silicate hydrate phase and the redox properties of the Au nanoparticles. A process for the conversion of ethanol to 1,3-BD, which uses our catalyst, is proposed and analyzed to determine the life-cycle GHG impact of the production of this product from biomass-derived ethanol. We show that 1,3-BD produced by our process can reduce GHG emissions by as much as 155 % relative to the conventional petroleum-based production of 1,3-BD. PMID- 27198472 TI - A combination of additives can synergically decrease acrylamide content in gingerbread without compromising sensory quality. AB - BACKGROUND: The present study tested whether replacement of the leavening agent ammonium carbonate by sodium hydrogen carbonate in combination with calcium cation and acidifying agent will synergically decrease acrylamide (AA) content in gingerbread. RESULTS: The type of leavening agent and the presence of Ca2+ and citric acid accounted for 33.6%, 13.2% and 53.2% of the explained variability of the AA content, respectively (P < 0.01). The AA content in gingerbread produced with (NH4 )2 CO3 alone was 186.5 ug kg-1 . Irrespective of other tested additives, NaHCO3 decreased (P < 0.05) AA content to 42% compared to (NH4 )2 CO3 . Combination of NaHCO3 + CaCl2 + citric acid in dough reduced (P < 0.05) AA content below the limit of detection (25 ug kg-1 ). The AA content in gingerbread (y; ug kg-1 ) decreased with an increasing number of additives used (x) according to the equation y = 158.8 - 47.94x (r2 = 0.42; P < 0.0001). A comprehensive sensory analysis did not indicate any significant deterioration (P > 0.05) in the organoleptic quality of gingerbread produced using calcium cation and citric acid. CONCLUSION: The present study demonstrates that the combination of additives NaHCO3 /Ca2+ /citric acid synergically decreases AA content in gingerbread without compromising the sensory quality. (c) 2016 Society of Chemical Industry. PMID- 27198473 TI - Promoting quality care in patients with cancer with limited English proficiency: perspectives of medical interpreters. PMID- 27198474 TI - Long-term mortality after parathyroidectomy among chronic kidney disease patients with secondary hyperparathyroidism: a systematic review and meta-analysis. AB - Parathyroidectomy (PTx) and medical treatments are both recommended for reducing serum intact parathyroid hormone (iPTH) and curing secondary hyperparathyroidism (sHPT) in patients with chronic kidney disease (CKD), but their therapeutic effects on long-term mortality are not well-known. Thus, we aim to assess such therapeutic effect of PTx. Electronic literatures published on Pubmed, Embase, and Cochrane Central Register of Controlled Trials in any language until 27 November 2015 were systematically searched. All literatures that compared outcomes (survival rate or mortality rate) between PTx-treated and medically treated CKD patients with sHPT were included. Finally, 13 cohort studies involving 22053 patients were included. Data were extracted from all included literatures in a standard form. The outcomes of all-cause and cardiovascular mortalities were assessed using DerSimonian and Laird's random effects model. We find PTx-treated versus medically-treated patients had a 28% reduction in all cause mortality and a 37% reduction in cardiovascular mortality. Thus, PTx versus medical treatments might reduce the risks of all-cause and cardiovascular mortalities in CKD patients with sHPT. Further studies with prospective and large sample clinical trials are needed to find out the real effect of PTx and to assess whether mortality rates differ among patterns of PTx. PMID- 27198475 TI - The use of community pharmacies in North West England: an observational study. AB - BACKGROUND: There are few studies of community pharmacy footfall and activity in the existing literature, especially by direct observation. OBJECTIVE: To describe the characteristics of counter interactions between pharmacy staff and customers. METHOD: Structured observation of all interactions between pharmacy staff and customers across the weekly opening hours of five pharmacies diverse in location and ownership. KEY FINDINGS: Three-quarters (76%) of observed interactions were associated with prescriptions, but a significant minority accessed cognitive services. CONCLUSIONS: Dispensing was the primary activity across the diverse range of pharmacies. Reasons for visits are diversifying into advice and services, particularly among younger users. PMID- 27198477 TI - Contemporary Accuracy of Digital Abdominal X-Ray for Follow-Up of Pure Calcium Urolithiasis: Is There Still a Role? AB - Radiological imaging remains the cornerstone of follow-up of patients with urolithiasis. Plain abdominal X-ray (XRKUB) of these patients is largely becoming obsolete in favor of noncontrast computed tomography of the abdomen and pelvis (CTKUB), which offers superior sensitivity and specificity. Contentiousness exists, however, related to the radiation doses associated with CT. Calcium oxalate remains the most common stone composition across most populations. These calculi are radiopaque and thus follow-up with XRKUB may be appropriate in some settings, avoiding the higher radiation doses associated with standard protocol CT. With the emergence of low-dose CT, however, and the modest accuracy of XRKUB, the ongoing role for XRKUB in the management of urolithiasis is debatable. In this study, we assessed the proportion of pure calcium urolithiasis visible on XRKUB to assess the utility of XRKUB for follow-up of pure calcium urolithiasis. Hospital laboratory databases were analysed to identify patients who had undergone urological intervention and extraction of urolithiasis composed of pure calcium salts, who had undergone CTKUB and XRKUB during the same episode for diagnosis of the calculus. One hundred five calculi were included and the imaging for each patient analyzed. 79/105 calculi (75%) identified on CT were visible on XRKUB. The median calculus visible on XRKUB was 7.0 mm (interquartile range [IQR] 5.0-10.0 mm), the median calculus not seen was 4.25 mm (IQR 3.5-7.0 mm) as measured on CT (p < 0.01). XRKUB accuracy varied according to calculus position within the renal tract. Calculi were most often visible in the renal pelvis and proximal ureter (86%), 50% of mid-ureteral and 72% of distal ureteral calculi were visible (p = 0.01). Until low-dose CT protocols become widely adopted, XRKUB still has a limited role in the management of pure calcium urolithiasis in selected patients. Due to its modest accuracy in many settings, this role is limited mainly to larger proximal urolithiasis. PMID- 27198479 TI - Evaluation of results from genome-wide studies of language and reading in a novel independent dataset. AB - Recent genome-wide association scans (GWAS) for reading and language abilities have pin-pointed promising new candidate loci. However, the potential contributions of these loci remain to be validated. In this study, we tested 17 of the most significantly associated single nucleotide polymorphisms (SNPs) from these GWAS studies (P < 10(-6) in the original studies) in a new independent population dataset from the Netherlands: known as Familial Influences on Literacy Abilities. This dataset comprised 483 children from 307 nuclear families and 505 adults (including parents of participating children), and provided adequate statistical power to detect the effects that were previously reported. The following measures of reading and language performance were collected: word reading fluency, nonword reading fluency, phonological awareness and rapid automatized naming. Two SNPs (rs12636438 and rs7187223) were associated with performance in multivariate and univariate testing, but these did not remain significant after correction for multiple testing. Another SNP (rs482700) was only nominally associated in the multivariate test. For the rest of the SNPs, we did not find supportive evidence of association. The findings may reflect differences between our study and the previous investigations with respect to the language of testing, the exact tests used and the recruitment criteria. Alternatively, most of the prior reported associations may have been false positives. A larger scale GWAS meta-analysis than those previously performed will likely be required to obtain robust insights into the genomic architecture underlying reading and language. PMID- 27198480 TI - Real-World Use of Prophylactic Antibiotics in Insertable Cardiac Monitor Procedures. AB - BACKGROUND: The use of prophylactic antibiotics during insertable cardiac monitor (ICM) procedures is a carryover of the common practice used with therapeutic cardiac implantable electronic devices. We sought to characterize the current practice of ICM insertion procedures to evaluate the influence of prophylactic antibiotic administration on the occurrence of infections. METHODS: We characterized insertion procedures and procedure-related infections from an ongoing multicenter registry (Reveal LINQ(TM) Registry). In order to accurately capture infections, only patients enrolled before or the day of insertion who also had a record of whether or not preoperative antibiotics were used were included in this analysis. Infections were defined based on the physician's assessment and reported upon occurrence. Patients were categorized into two analysis cohorts based on prophylactic antibiotic use. RESULTS: We analyzed 375 patients from 14 U.S. centers (age 63.1 +/- 15.6 years; male 54.1%). Approximately two-thirds of patients (66.4%) did not receive any preprocedural antibiotics. The overall infection rate was 1.1% (0.3-2.7% confidence interval [CI]) and corresponded to four events. In the group that did not receive preprocedural antibiotics, there were two minor infections (0.8%, [0.1-2.9% CI]), whereas in the group receiving preprocedural antibiotics a serious and a minor infection occurred (1.6%, [0.2-5.6% CI]); this serious infection resulted in an explant. CONCLUSIONS: Current real-world practice shows that ICM insertions are increasingly performed without the use of prophylactic antibiotics, which is associated with a very low infection rate. PMID- 27198481 TI - Effectiveness of interventions for adults with mild to moderate intellectual disabilities and mental health problems: systematic review and meta-analysis. AB - BACKGROUND: There is a lack of available evidence in relation to the effectiveness of interventions for adults with mild to moderate intellectual disability and mental health problems. AIMS: To evaluate the efficacy of interventions for adults with mild to moderate intellectual disabilities and co occurring mental health problems. METHOD: An electronic literature search of the databases Medline, EMBASE, PsycINFO and EBM Reviews aimed at identifying randomised controlled trials (RCTs) and controlled trials testing any type of intervention (psychotherapy, biological or system level) for people with mild to moderate intellectual disabilities (IQ score 35-69) targeting comorbid mental health problems. Additionally a meta-analysis was conducted. RESULTS: Twelve studies met the inclusion criteria. No significant effect was found for the predefined outcome domains behavioural problems, depression, anxiety, quality of life and functioning. The effect size for depression (d = 0.49) was moderate but non-significant. Quality of studies was moderate and heterogeneity was high. CONCLUSIONS: There is no compelling evidence supporting interventions aiming at improving mental health problems in people with mild to moderate intellectual disability. The number of available trials is too low for definite conclusions. Some interventions are promising and should be evaluated further in larger and more rigorous trials. PMID- 27198478 TI - An Infectious cDNA Clone of Zika Virus to Study Viral Virulence, Mosquito Transmission, and Antiviral Inhibitors. AB - The Asian lineage of Zika virus (ZIKV) has recently caused epidemics and severe disease. Unraveling the mechanisms causing increased viral transmissibility and disease severity requires experimental systems. We report an infectious cDNA clone of ZIKV that was generated using a clinical isolate of the Asian lineage. The cDNA clone-derived RNA is infectious in cells, generating recombinant ZIKV. The recombinant virus is virulent in established ZIKV mouse models, leading to neurological signs relevant to human disease. Additionally, recombinant ZIKV is infectious for Aedes aegypti and thus provides a means to examine virus transmission. The infectious cDNA clone was further used to generate a luciferase ZIKV that exhibited sensitivity to a panflavivirus inhibitor, highlighting its potential utility for antiviral screening. This ZIKV reverse genetic system, together with mouse and mosquito infection models, may help identify viral determinants of human virulence and mosquito transmission as well as inform vaccine and therapeutic strategies. PMID- 27198482 TI - Initial depression severity and response to antidepressants v. placebo: patient level data analysis from 34 randomised controlled trials. AB - Several often-cited meta-analyses have reported that the efficacy of antidepressant medications depends on the severity of depression. They found that drug-placebo differences increased as a function of initial severity, which was attributed to decreased responsiveness to placebo among patients with severe depression rather than to increased responsiveness to medication. We retested this using patient-level data and also undertaking a meta-analysis of trial-level data from 34 randomised placebo controlled trials (n = 10 737) from the NEWMEDS registry. Although our trial-level data support prevous findings, patient-level data did not show any significant effect of initial depression severity on drug v. placebo difference. PMID- 27198483 TI - Shared treatment decision-making and empowerment-related outcomes in psychosis: systematic review and meta-analysis. AB - BACKGROUND: In the UK almost 60% of people with a diagnosis of schizophrenia who use mental health services say they are not involved in decisions about their treatment. Guidelines and policy documents recommend that shared decision-making should be implemented, yet whether it leads to greater treatment-related empowerment for this group has not been systematically assessed. AIMS: To examine the effects of shared decision-making on indices of treatment-related empowerment of people with psychosis. METHOD: We conducted a systematic review and meta analysis of randomised controlled trials (RCTs) of shared decision-making concerning current or future treatment for psychosis (PROSPERO registration CRD42013006161). Primary outcomes were indices of treatment-related empowerment and objective coercion (compulsory treatment). Secondary outcomes were treatment decision-making ability and the quality of the therapeutic relationship. RESULTS: We identified 11 RCTs. Small beneficial effects of increased shared decision making were found on indices of treatment-related empowerment (6 RCTs; g = 0.30, 95% CI 0.09-0.51), although the effect was smaller if trials with >25% missing data were excluded. There was a trend towards shared decision-making for future care leading to reduced use of compulsory treatment over 15-18 months (3 RCTs; RR = 0.59, 95% CI 0.35-1.02), with a number needed to treat of approximately 10 (95% CI 5-infinity). No clear effect on treatment decision-making ability (3 RCTs) or the quality of the therapeutic relationship (8 RCTs) was found, but data were heterogeneous. CONCLUSIONS: For people with psychosis the implementation of shared treatment decision-making appears to have small beneficial effects on indices of treatment-related empowerment, but more direct evidence is required. PMID- 27198484 TI - Repetitive transcranial magnetic stimulation for generalised anxiety disorder: a pilot randomised, double-blind, sham-controlled trial. AB - BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) holds promise for treating generalised anxiety disorder (GAD) but has only been studied in uncontrolled research. AIMS: This is the first randomised controlled trial (clinicaltrials.gov: NCT01659736) to investigate the efficacy and neural correlates of rTMS in GAD. METHOD: Twenty five participants (active n = 13; sham, n = 12) enrolled. rTMS was targeted at the right dorsolateral prefrontal cortex (DLPFC, 1 Hz, 90% resting motor threshold). RESULTS: Response and remission rates were higher in the active v. sham groups and there were significant group * time interactions for anxiety, worry and depressive symptoms, favouring active v. sham. In addition, right DLPFC activation during a decision-making gambling task increased at post-treatment for active rTMS only, and changes in neuroactivation correlated significantly with changes in worry symptoms. CONCLUSIONS: Findings provide preliminary evidence that rTMS may improve GAD symptoms in association with modifying neural activity in the stimulation site. PMID- 27198485 TI - Cortical thickness in obsessive-compulsive disorder: multisite mega-analysis of 780 brain scans from six centres. AB - BACKGROUND: There is accumulating evidence for the role of fronto-striatal and associated circuits in obsessive-compulsive disorder (OCD) but limited and conflicting data on alterations in cortical thickness. AIMS: To investigate alterations in cortical thickness and subcortical volume in OCD. METHOD: In total, 412 patients with OCD and 368 healthy adults underwent magnetic resonance imaging scans. Between-group analysis of covariance of cortical thickness and subcortical volumes was performed and regression analyses undertaken. RESULTS: Significantly decreased cortical thickness was found in the OCD group compared with controls in the superior and inferior frontal, precentral, posterior cingulate, middle temporal, inferior parietal and precuneus gyri. There was also a group * age interaction in the parietal cortex, with increased thinning with age in the OCD group relative to controls. CONCLUSIONS: Our findings are partially consistent with earlier work, suggesting that group differences in grey matter volume and cortical thickness could relate to the same underlying pathology of OCD. They partially support a frontostriatal model of OCD, but also suggest that limbic, temporal and parietal regions play a role in the pathophysiology of the disorder. The group * age interaction effects may be the result of altered neuroplasticity. PMID- 27198486 TI - Apolipoproteins L control cell death triggered by TLR3/TRIF signaling in dendritic cells. AB - Apolipoproteins L (ApoLs) are Bcl-2-like proteins expressed under inflammatory conditions in myeloid and endothelial cells. We found that Toll-like receptor (TLR) stimuli, particularly the viral mimetic polyinosinic:polycytidylic acid (poly(I:C)), specifically induce ApoLs7/11 subfamilies in murine CD8alpha(+) dendritic cells (DCs). This induction requires the TLR3/TRIF (where TRIF is TIR domain containing adapter-inducing interferon beta) signaling pathway and is dependent on IFN-beta in all ApoLs subfamilies except for ApoL7c. Poly(I:C) treatment of DCs is also associated with induction of both cell death and autophagy. ApoLs expression is related to promotion of DC death by poly(I:C), as ApoLs7/11 knockdown increases DC survival and ApoLs7 are associated with the anti apoptotic protein Bcl-xL (where Bcl-xL is B-cell lymphoma extra large). Similarly, in human monocyte-derived DCs poly(I:C) induces both cell death and the expression of ApoLs, principally ApoL3. Finally, the BH3-like peptide of ApoLs appears to be involved in the DC death-promoting activity. We would like to propose that ApoLs are involved in cell death linked to activation of DCs by viral stimuli. PMID- 27198487 TI - A 2-Gene Panel Derived From Prostate Cancer-Enhanced Transcripts in Whole Blood Is Prognostic for Survival and Predicts Treatment Benefit in Metastatic Castration-Resistant Prostate Cancer. AB - BACKGROUND: To determine a prognostic model derived from prostate cancer-enhanced transcripts in whole blood of castration-resistant prostate cancer (CRPC) patients and explore its applicability as a surrogate of treatment response. METHODS: Six out of twenty-three selected transcripts were identified as specific for detection of metastatic prostate cancer cells in peripheral blood using quantitative polymerase chain reaction (qPCR). Their prognostic value was explored in whole blood samples of a training cohort (n = 22 CRPC patients, New York, USA). A resulting 2-gene panel (2GP) including KLK2 and TMPRSS2 was validated in an independent cohort with pre- and post-treatment blood draws after 9-16 weeks of systemic treament (n = 86 CRPC patients, Munich, Germany). Overall survival (OS), prostate-specific antigen progression-free survival (PSA-PFS), and clinical PFS were analyzed. Kaplan-Meier and cox regression analyses were performed. RESULTS: An unfavorable 2GP (>=1 marker positive) identified patients with poor survival (median OS 10.0 months [95%CI 5.7-14.2] vs. not reached; P = 0.023). This was validated in an independent cohort at pre-treatment (median OS 7.8 [95%CI 6.5-9.2] vs. 17.3 months [95%CI 10.7-23.8]; P = 0.004) and post treatment blood draw (median OS 5.0 [95%CI 0.0-10.0] vs. 18.0 months [95%CI 9.5 26.6]; P = 0.003). The 2GP independently predicted OS on multivariate analysis (hazard ratio 2.1 [95%CI 1.1-4.0]; P = 0.034) and performed better than PSA decline at correlation with OS. Conversion to favorable 2GP during treatment correlated with improved OS (7.8 to 20.9 months), PSA-PFS (2.8 to 12.0 months), and clinical PFS (4.6 to 8.0 months). CONCLUSIONS: The established 2GP is prognostic for survival at pre- and post-treatment blood draw in CRPC patients and conversion to favorable 2GP predicts treatment benefit. Prostate 76:1160 1168, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27198488 TI - Sofosbuvir and daclatasvir. PMID- 27198489 TI - Antiepileptic effect of fisetin in iron-induced experimental model of traumatic epilepsy in rats in the light of electrophysiological, biochemical, and behavioral observations. AB - BACKGROUND: Traumatic epilepsy is defined by episodes of recurring seizures secondary to severe brain injury. Though drugs are found effective to control seizures, their long-term use have been observed to increase reactive oxygen species in animals. Flavonoid fisetin, a natural bioactive phytonutrient reported to exert anticonvulsive effect in experimental seizure models. But, trauma induced seizures could not be prevented by anticonvulsants was reported in some clinical studies. OBJECTIVE: To study the effect of fisetin on epileptiform electrographic activity in iron-induced traumatic epilepsy and also the probable reason behind the effect in rats. METHODS: Fisetin pretreatment (20 mg/kg body wt., p.o.) of rats for 12 weeks were chosen followed by injecting iron (5 ul, 100 mM) stereotaxically to generate iron-induced epilepsy. Experimental design include electrophysiological study (electroencephalograph in correlation with multiple unit activity (MUA) in the cortex and CA1 subfield of the hippocampus; spectral analysis of seizure and seizure-associated behavioral study (Morris water maze for spatial learning, open-field test for anxiety) and biochemical study (lipid peroxidation, Na+,K+-ATPase activity) in both the cortex and the hippocampus. RESULTS: Fisetin pretreatment was found to prevent the development of iron-induced electrical seizure and decrease the corresponding MUA in the cortex (*P?0.05) as well as in the hippocampus (***P?0.001). Fisetin pretreatment decreased the lipid peroxides (*P?0.05) and retained the Na+,K+-ATPase activity (*P?0.05) which was found altered in the epileptic animals and also found to attenuate the seizure-associated cognitive dysfunctions. CONCLUSION: This study demonstrated the antiepileptic action of fisetin in iron-induced model of epileptic rats by inhibiting oxidative stress. PMID- 27198491 TI - Is the naturalistic course of depression in older people related to received support over time? Results from a longitudinal population-based study. AB - OBJECTIVES: To test the interrelation of the naturalistic course of depression in older people with long-term support received. DESIGN: Longitudinal cohort study. METHODS: A sample of 277 adults age 55-85 years participating in the Longitudinal Aging Study Amsterdam, with clinically relevant depressive symptoms at baseline (scores >=16 on the Center for Epidemiological Studies Depression Scale) were followed up over a period of 13 years. General estimating equations were used to examine the relation between depression course and emotional/instrumental support received over time. In addition, partner status, gender, and age were tested as modifiers. RESULTS: A 2-way interaction between depression courses types and time showed significant differences in instrumental support received over time in older people with a late-life depression. Three-way interactions showed that associations between depression course and support variables were modified by gender and partner status. CONCLUSION: Both men and singles, with a chronic course of depression may be at risk to lose emotional and instrumental support over time. Professional attention is needed to prevent a chronic course of late life depression, and to preserve personal social networks. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27198492 TI - Nonmetallization and band inversion in beryllium dicarbide at high pressure. AB - Carbides have attracted much attention owing to their interesting physical and chemical properties. Here, we systematically investigated global energetically stable structures of BeC2 in the pressure range of 0-100 GPa using a first principles structural search. A transition from the ambient-pressure alpha-phase to the high-pressure beta-phase was theoretically predicted. Chemical bonding analysis revealed that the predicted phase transition is associated with the transformation from sp(2) to sp(3) C-C hybridization. The electrical conductivity of the high-pressure phase changed from a metal (alpha-phase) to a narrow bandgap semiconductor (beta-phase), and the beta-phase had an inverted band structure with positive pressure dependence. Interestingly, the beta-phase was a topological insulator with the metallic surface states protected by the time reversal symmetry of the crystal. The results indicate that pressure modulates the electronic band structure of BeC2, which is an important finding for fundamental physics and for a wide range of potential applications in electronic devices. PMID- 27198493 TI - Challenges in the pain assessment during neonatal transport: an update. AB - Neonatal transport is a highly specialized medical service that shifts critically ill neonates between hospitals for on-going care. In other words, it is an extension of the Neonatal Intensive Care Unit (NICU), which provides intensive care to critical ill neonates during transport. Furthermore, pain assessment and management is a crucial element during neonatal transport. However despite significant advances over the last 20 years in relation to our understanding of pain mechanisms in the neonates, the immediate long and short term consequences of neonatal pain along with proliferation of pain assessment measures, there continues to be reports of neonates in a variety of settings suffering needlessly from acute, prolonged, persistent and chronic pain. The central focus of the present review article is to put light on the existing challenges accompanying neonatal pain assessment during transport. PMID- 27198490 TI - Fungal communities in sediments of subtropical Chinese seas as estimated by DNA metabarcoding. AB - Ribosomal RNA internal transcribed spacer-1 (ITS1) metabarcoding was used to investigate the distribution patterns of fungal communities and the factors influencing these patterns in subtropical Chinese seas, including the southern and northern Yellow Sea and the Bohai Sea. These seas were found to harbor high levels of fungal diversity, with 816 operational taxonomic units (OTUs) that span 130 known genera, 36 orders, 14 classes and 5 phyla. Ascomycota was the most abundant phylum, containing 72.18% and 79.61% of all OTUs and sequences, respectively, followed by Basidiomycota (19.98%, 18.64%), Zygomycota (1.10%, 0.11%), Chytridiomycota (0.25%, 0.04%) and Rozellomycota (0.12%, 0.006%). The compositions of fungal communities across these three sea regions were found to be vary, which may be attributed to sediment source, geographical distance, latitude and some environmental factors such as the temperature and salinity of bottom water, water depth, total nitrogen, and the ratio of total organic carbon to nitrogen. Among these environmental factors, the temperature of bottom water is the most important driver that governs the distribution patterns of fungal communities across the sampled seas. Our data also suggest that the cold-water mass of the Yellow Sea likely balances competitive relationships between fungal taxa rather than increasing species richness levels. PMID- 27198494 TI - A study on evaluation of laparoscopic surgical approach for pediatric appendix abscess. AB - BACKGROUND: Our main objective was to investigate and compare chosen time laparoscopic surgery to traditional open surgery and to analyze whether laparoscopic surgery is safe and feasible for pediatric appendix abscess in emergency. METHODS: This retrospective study consisted of three groups of patients designated as group A, group B, group C and the preoperative and postoperative clinical characteristics were analyzed and compared. Group A comprised of 63 patients of appendix abscess which has been treated by laparoscopic surgery from January 2011 to December 2014. Group B comprised of 60 patients who had undergone pediatric appendix abscess laparotomy and group C comprised of 35 cases who had undergone time-selective laparoscopic appendix ablation surgery after receiving anti-inflammatory treatment. RESULTS: The average operation time during which all the appendix ablated successfully between group A and group B patients was not significantly different (P>0.05), meanwhile, operation time was significantly less for group C patients in comparison with group A patients (P<0.05). The incidence of postoperative complications among patients of group A was significantly lower than that of group B (P<0.05), while, these complications were similarly distributed between group A and group C (P>0.05). The duration of hospitalization among patients of group B (P<0.05) and group C (P<0.05) was significantly higher in comparison with group A patients. CONCLUSION: As long as preoperative and perioperative periods are appropriately dealt with, laparoscopic surgery is safe and feasible to pediatric appendix abscess in emergency. PMID- 27198495 TI - Development and feasibility testing of an oral hygiene intervention for stroke unit care. AB - OBJECTIVE: To develop an oral hygiene complex intervention and evaluate its feasibility in a single UK stroke centre. BACKGROUND: Oral hygiene interventions might improve clinical outcomes after stroke but evidence-based practice is lacking. MATERIALS AND METHODS: We used a sequential mixed methods approach and developed an oral hygiene complex intervention comprising: (i) web-based education and 'hands-on' practical training for stroke unit nursing staff, (ii) a pragmatic oral hygiene protocol consisting of twice-daily powered (or manual if preferred) brushing with chlorhexidine gel (or non-foaming toothpaste) +/- denture care. We evaluated feasibility of (i) the staff education and training and (ii) the oral hygiene protocol in consenting inpatients with confirmed stroke, requiring assistance with at least one aspect of personal care. RESULTS: The staff education and training were feasible, acceptable and raised knowledge and awareness. Several barriers to completing the education and training were identified. The oral hygiene protocol was feasible and well-tolerated. 22% of eligible patients screened declined participation in the study. Twenty-nine patients (median age = 78 year; National Institutes of Health Stroke Scale score = 8.5; 73% dentate) were recruited at a median of 7 days from stroke onset. 97% of participants chose the default chlorhexidine-based protocol; the remainder chose the non-foaming toothpaste-based protocol. The mouth hygiene protocol was administered as prescribed on 95% of occasions, over a median duration of 28 days. There were no adverse events attributed to the oral hygiene protocol. CONCLUSION: Our oral hygiene complex intervention was feasible in a single UK stroke centre. Further studies to optimise patient selection, model health economics and explore efficacy are now required. PMID- 27198497 TI - Graft-versus-host disease in paediatric solid organ transplantation: A review of the literature. AB - GvHD is a rare and serious complication of organ transplantation. The literature is sparse following solid organ transplantation. The aim of this report was to review the literature of GvHD in paediatric solid organ transplantation. We searched PubMed for English-language full-text manuscripts between 1990 and 2015 for eligible studies. A total of 28 publications were found pertaining to paediatric GvHD following solid organ transplantation. GvHD had a mean incidence of 11% (range 8.3-13.4%) following SBTx and 1.5% following liver transplantation. Where described, the most common sites for presentation of GvHD were the skin (87%), the native GI tract (43%), the lungs (7%), the eyes (4%), HA (4%), and the kidneys (1%). Diagnosis was confirmed with biopsy (93%) and/or chimerism (41%). Treatments used include steroids (80%), of which 75% showed partial or complete resolution. Mortality was 33.3% (range 0-100%). Novel therapies include ECP and MSC therapy. GvHD is a rare but serious disease with high mortality. Novel therapies may offer hope in the future, but currently there is limited evidence for their efficacy in the context of intestinal or liver transplantation. PMID- 27198496 TI - Insights in the Fruit Flesh Browning Mechanisms in Solanum melongena Genetic Lines with Opposite Postcut Behavior. AB - Color, taste, flavor, nutritional value, and shelf life are important factors determining quality and healthiness of food and vegetables. These factors are strongly affected by browning processes, occurring after fruit or vegetable cutting. Characterization of ten eggplant genotypes for chlorogenic acid (CGA) content, total phenols (TP), polyphenoloxidase (PPO) activity, and browning tendency corroborated a lack of significant correlations between biochemical factors and fruit flesh browning. Further in-depth molecular and biochemical analyses of two divergent eggplant genetic lines, AM199 (high browning) and AM086 (low browning), within 30 min from cutting, highlighted differences in the physiological mechanisms underlying the browning process. qRT-PCR analysis revealed distinct activation mechanisms of CGA biosynthetic and PPO genes in the two genetic lines. Metabolic data on CGA, sugars, and ascorbic acid contents confirmed that their different browning tendency matched with different metabolic responses to cutting. Our findings suggest that the complex mechanism of flesh browning in the two eggplant genetic lines might be mediated by multiple specific factors. PMID- 27198499 TI - Introduction. PMID- 27198498 TI - Diacylglycerol-mediated regulation of Aplysia bag cell neuron excitability requires protein kinase C. AB - KEY POINTS: In Aplysia, reproduction is initiated by the bag cell neurons and a prolonged period of enhanced excitability known as the afterdischarge. Phosphoinositide turnover is upregulated during the afterdischarge resulting in the hydrolysis of phosphatidylinositol-4,5-bisphosphate by phospholipase C (PLC) and the release of diacylglycerol (DAG) and inositol trisphosphate (IP3 ). In whole-cell voltage-clamped cultured bag cell neurons, 1-oleoyl-2-acetyl-sn glycerol (OAG), a synthetic DAG analogue, activates a dose-dependent, transient, inward current (IOAG ) that is enhanced by IP3 , mimicked by PLC activation and dependent on basal protein kinase C (PKC) activity. OAG depolarizes bag cell neurons and triggers action potential firing in culture, and prolongs electrically stimulated afterdischarges in intact bag cell neuron clusters ex vivo. Although PKC alone cannot activate the current, it is required for IOAG ; this is the first description of required obligate PKC activity working in concert with PLC, DAG and IP3 to maintain the depolarization required for prolonged excitability in Aplysia reproduction. ABSTRACT: Following synaptic input, the bag cell neurons of Aplysia undergo a long-term afterdischarge of action potentials to secrete egg-laying hormone and initiate reproduction. Early in the afterdischarge, phospholipase C (PLC) hydrolyses phosphatidylinositol-4,5 bisphosphate into inositol trisphosphate (IP3 ) and diacylglycerol (DAG). In Aplysia, little is known about the action of DAG, or any interaction with IP3 ; thus, we examined the effects of a synthetic DAG analogue, 1-oleoyl-2-acetyl-sn glycerol (OAG), on whole-cell voltage-clamped cultured bag cell neurons. OAG induced a large, prolonged, Ca(2+) -permeable, concentration-dependent inward current (IOAG ) that reversed at ~-20 mV and was enhanced by intracellular IP3 . A similar current was evoked by either another DAG analogue, 1,2-dioctanoyl-sn glycerol (DOG), or activating PLC with N-(3-trifluoromethylphenyl)-2,4,6 trimethylbenzenesulfonamide (m-3M3FBS). IOAG was reduced by the general cation channel blockers Gd(3+) or flufenamic acid. Work in other systems indicated that OAG activates channels independently of protein kinase C (PKC); however, we found pretreating bag cell neurons with any of the PKC inhibitors bisindolylmaleimide, sphinganine, or H7, attenuated IOAG . However, stimulating PKC with phorbol 12 myristate 13-acetate (PMA) did not evoke current or enhance IOAG ; moreover, unlike PMA, OAG failed to trigger PKC, as confirmed by an independent bioassay. Finally, OAG or m-3M3FBS depolarized cultured neurons, and while OAG did not provoke afterdischarges from bag cell neurons in the nervous system, it did double the duration of synaptically elicited afterdischarges. To our knowledge, this is the first report of obligate PKC activity for IOAG gating. An interaction between phosphoinositol metabolites and PKC could control the cation channel to influence afterdischarge duration. PMID- 27198501 TI - A dual-detector optical receiver for PDM signals detection. AB - We propose and fabricate a silicon based dual-detector optical receiver, which consists of a two dimensional (2D) grating coupler (GC) and two separate germanium photodetectors (Ge PDs). The 2D GC performs polarization diversity, and thus demultiplexing and detection for polarization division multiplexed (PDM) signals can be achieved. Through a specific design with double-sides illumination, the space charge density can be reduced and the responsivity and saturation power can be improved significantly. The measured dark current, responsivity and bandwidth are 0.86 MUA, 1.06 A/W and 36 GHz under 3 V reverse biased voltage, respectively. Both DC currents and eye diagrams are measured for the proposed device and the results validate its performance successfully. The power penalty between the single and dual polarized signals is about 1.9 dB under 10 and 20 Gb/s cases for both the two Ge PDs. The proposed direct detection (DD) for PDM signals with high speed, high responsivity and large saturation power is cost-effective and promising for short reach optical communication. PMID- 27198500 TI - Illegitimate RAG-mediated recombination events are involved in IKZF1 Delta3-6 deletion in BCR-ABL1 lymphoblastic leukaemia. AB - Breakpoint cluster region-Abelson murine leukaemia viral oncogene homologue 1 (BCR-ABL1), encoded by the Philadelphia (Ph) chromosome, is the characteristic of chronic myeloid leukaemia (CML) and a subset of acute lymphoblastic leukaemia (ALL). We demonstrated that expression of the Ik6 transcript, which lacked exons 3-6, was observed exclusively in BCR-ABL1(+) B ALL and lymphoid blast crisis CML (BC-CML) patients harbouring the IKZF1 Delta3-6 deletion. To confirm the hypothesis that illegitimate recombination activating gene protein (RAG)-mediated recombination events are involved in IKZF1 Delta3-6 deletion in BCR-ABL1 lymphoblastic leukaemia, we first demonstrated that the expression rates of RAG1 and RAG2, collectively called RAG, were higher in ALL and BC-CML (lymphoid). Notably, analysis of relationships among RAG, BCR-ABL1 and Ikaros 6 (Ik6) showed that Ik6 can be generated only if RAG and BCR-ABL1 are co-existing. The sequencing data showed that the deleted segments of introns 2 and 6 contained cryptic recombination signal sequences (cRSSs) and frequently had non-template nucleotides inserted between breakpoints. Furthermore, we used chromatin immunoprecipitation (ChIP) technology and demonstrated that the sequences directly flanking IKZF1 Delta3-6 deletion breakpoints have significantly higher levels of histone H3 lysine 4 trimethylation (H3K4me3) modifications. Overall, RAG expression, good-quality cRSS and a specific chromatin modification, H3K4me3, satisfy the conditions of RAG's off-target effects on IKZF1. Our work provides evidence for RAG-mediated IKZF1 Delta3-6 deletion. Our results raise the prospect that RAG is a valuable biomarker in disease surveillance. Dissecting the contribution of RAG should not only provide valuable mechanistic insights, but will also lead to a new therapeutic direction. PMID- 27198503 TI - Life and death of not so "bare" bubbles. AB - In this paper, we investigate how the drainage and rupture of surfactant stabilised bubbles floating at the surface of a liquid pool depend on the concentration of surface-active molecules in water. Drainage measurements at the apex of bubbles indicate that the flow profile is increasingly plug-like as the surfactant concentration is decreased from several times the critical micellar concentration (cmc) to just below the cmc. High-speed observations of bubble bursting reveal that the position at which a hole nucleates in the bubble cap also depends on the surfactant concentration. On average, the rupture is initiated close to the bubble foot for low concentrations (=15. Factors associated with a higher number of LNs were melanoma (p < 0.001), visualization of the axillary vein (p = 0.03), and long thoracic nerve (p = 0.04). There was no association with age, body mass index, number of positive LNs, neoadjuvant chemotherapy, or matted LNs. Mean ALND photograph score was 4.8 (SD 1.3). A 1-point change in total score increased the mean LN count by 2.4 (p = 0.002). Correlations for interrater reliability varied from 0.27 to 0.62. CONCLUSIONS: Photographic visualization of axillary anatomic structures correlates with the number of LNs identified on pathology. These findings support initiating a larger study with more surgeons to define the optimal photo metrics of an adequate ALND. PMID- 27198513 TI - Impact of Age on Risk of Recurrence of Ductal Carcinoma In Situ: Outcomes of 2996 Women Treated with Breast-Conserving Surgery Over 30 Years. AB - BACKGROUND: Age is a known risk factor for recurrence in women with ductal carcinoma in situ (DCIS) treated with breast-conserving surgery (BCS). We explored the relationship between age, other risk factors, and recurrence. METHODS: Using a prospectively maintained database of DCIS patients undergoing BCS from 1978 to 2010, the association of age and recurrence risk was analyzed using Kaplan-Meier estimates, multivariable analysis, and competing risk multivariable analysis. RESULTS: Overall, 2996 cases were identified. Median follow-up for those without recurrence was 75 months; 732 were followed for >=10 years, and 363 (12 %) had recurrence [192 (53 %) DCIS, 160 (44 %) invasive, 11 (3 %) unknown]. Risk of recurrence decreased with age, even after adjustment for eight clinicopathologic variables on multivariable analysis [hazard ratios (HR), with <40 years of age as the reference: 40-49 years, 0.82 (p = 0.36), 50-59 years, 0.46 (p = 0.0005), 60-69 years, 0.50 (p = 0.003), 70-79 years, 0.56 (p = 0.02), >=80 years, 0.21 (p = 0.0015)]. This association persisted for cohorts with and without radiation therapy. Using competing risk multivariable analysis, the effect of age on invasive recurrence was empirically stronger than for DCIS recurrence. Ten-year invasive recurrence was 16 and 6.5 % in women <40 years of age and women >=40 years of age, respectively. Only 0.6 % of the population ultimately developed distant disease; those <40 years of age constituted 4.7 % (141/2996) of the population, but 21 % (4/19) of those developed distant disease. CONCLUSIONS: The risk of recurrence of DCIS decreases with age. This effect is particularly strong at the extremes of age and is independent of other clinicopathologic factors. The oldest women are at low risk of recurrence, while the youngest women have a higher overall, and especially invasive, recurrence rate, although mortality remains low. These findings should be incorporated into risk/benefit discussions of treatment options. PMID- 27198515 TI - Brefeldin A reduces tumor necrosis factor-alpha-stimulated production of inflammatory mediators by suppressing the Akt, mTOR, and NF-kappaB pathways in human keratinocytes. AB - Keratinocytes may play an important role in the pathogenesis of inflammatory skin diseases. Brefeldin A has been shown to attenuate the production and secretion of chemical mediators involved in inflammation and immune responses. However, the effect of brefeldin A on the TNF-alpha-stimulated production of inflammatory mediators in keratinocytes has not been studied. We investigated the effect of brefeldin A on the TNF-alpha-stimulated production of inflammatory mediators using HaCaT cells and primary keratinocytes in relation to the Akt, mTOR, and NF kappaB pathways, which regulates the transcription genes involved in immune and inflammatory responses. Brefeldin A, Akt inhibitor, Bay 11-7085 (an inhibitor of NF-kappaB activation), and rapamycin (mTOR inhibitor) inhibited the TNF-alpha stimulated productions of inflammatory mediators, and activations of Akt, mTOR, and NF-kappaB in keratinocytes. The results show that brefeldin A appears to attenuate TNF-alpha-stimulated inflammatory mediator production in keratinocytes by suppressing the activation of the Akt, mTOR, and NF-kappaB pathways. PMID- 27198514 TI - Febuxostat, a novel xanthine oxidoreductase inhibitor, improves hypertension and endothelial dysfunction in spontaneously hypertensive rats. AB - Xanthine oxidase (XO) is an enzyme responsible for the production of uric acid. XO produces considerable amount of oxidative stress throughout the body. To date, however, its pathophysiologic role in hypertension and endothelial dysfunction still remains controversial. To explore the possible involvement of XO-derived oxidative stress in the pathophysiology of vascular dysfunction, by use of a selective XO inhibitor, febuxostat, we investigated the impact of pharmacological inhibition of XO on hypertension and vascular endothelial dysfunction in spontaneously hypertensive rats (SHRs). Sixteen-week-old SHR and normotensive Wistar-Kyoto (WKY) rats were treated with tap water (control) or water containing febuxostat (3 mg/kg/day) for 6 weeks. Systolic blood pressure (SBP) in febuxostat treated SHR (220 +/- 3 mmHg) was significantly (P < 0.05) decreased compared with the control SHR (236 +/- 4 mmHg) while SBP in febuxostat-treated WKY was constant. Acetylcholine-induced endothelium-dependent relaxation in aortas from febuxostat-treated SHR was significantly (P < 0.05) improved compared with the control SHR, whereas relaxation in response to sodium nitroprusside was not changed. Vascular XO activity and tissue nitrotyrosine level, a representative indicator of local oxidative stress, were considerably elevated in the control SHR compared with the control WKY, and this increment was abolished by febuxostat. Our results suggest that exaggerated XO activity and resultant increase in oxidative stress in this experimental model contribute to the hypertension and endothelial dysfunction, thereby supporting a notion that pharmacological inhibition of XO is valuable not only for hyperuricemia but also for treating hypertension and related endothelial dysfunction in human clinics. PMID- 27198516 TI - Combinational effects of prebiotic oligosaccharides on bifidobacterial growth and host gene expression in a simplified mixed culture model and neonatal mice. AB - It is important to provide formula-fed infants with a bifidobacteria-enriched gut microbiota similar to those of breastfed infants to ensure intestinal health. Prebiotics, such as certain oligosaccharides, are a useful solution to this problem, but the combinational benefits of these oligosaccharides have not been evaluated. This study investigated the benefits of oligosaccharide combinations and screened for an optimal combination of oligosaccharides to promote healthy gut microbiota of formula-fed infants. In vitro and in vivo experiments were performed to assess the bifidogenic effects of lactulose (LAC) alone and LAC combined with raffinose (RAF) and/or galacto-oligosaccharide (GOS), using a mixed culture model and neonatal mice orally administered with these oligosaccharides and Bifidobacterium breve. In the in vitro culture model, the combination of the three oligosaccharides (LAC-RAF-GOS) significantly increased cell numbers of B. breve and Bifidobacterium longum (P<0.05) compared with either LAC alone or the combination of two oligosaccharides, and resulted in the production of SCFA under anaerobic conditions. In the in vivo experiment, the LAC-RAF-GOS combination significantly increased cell numbers of B. breve and Bacteroidetes in the large intestinal content (P<0.05) and increased acetate concentrations in the caecal content and serum of neonatal mice. Genes related to metabolism and immune responses were differentially expressed in the liver and large intestine of mice administered with LAC-RAF-GOS. These results indicate a synergistic effect of the LAC-RAF-GOS combination on the growth of bifidobacteria and reveal possible benefits of this combination to the gut microbiota and health of infants. PMID- 27198517 TI - Older Gay Men and Their Support Convoys. AB - Objective: We used the convoy model and the network type construct to identify the relationship quality profiles found among older gay men and to examine how they define a satisfactory network. Method: We used a network mapping strategy and in-depth qualitative interviews with 20 participants in Atlanta. During the interviews, all network members were discussed, regardless of relationship or map position. Results: For participants, having people in their lives with whom they could fully be "out" as gay men (authenticity) was at the root of a quality network. This allowed them to develop emotional closeness (intimacy), which, in part, provided a foundation of social support. Participants' discussion of network quality, which reflected authenticity, intimacy, and social support, revealed high, moderate, and low quality network types. Discussion: Our findings diversify knowledge of the network type construct, provide a deeper understanding of its qualitative features, and give voice to this often-invisible group, situating meaning within their social-historical context. The findings suggest that the meaning of a quality network is contextual and culturally specific, varying across groups of older adults. PMID- 27198518 TI - The Role of Food Fortification in Addressing Iron Deficiency in Infants and Young Children. AB - Iron deficiency, one of the most widespread nutritional disorders, affects millions of people in emerging economies and, increasingly, in industrialized countries. Due to the high iron requirements during growth and development, infants and young children are among those most severely affected by iron deficiency. Iron deficiency that occurs during the critical phases of early life development has long-lasting health consequences that are reflected in increased risk of disease, reduced economic productivity and premature death, underscoring the importance of infants and young children as a key target group for addressing iron deficiency. This chapter focuses on the use of fortified foods as a cost effective mechanism to address iron deficiency in this particularly vulnerable subpopulation. Nutritional policies that include food fortification need to be implemented within the context of effective public-private partnerships in order to address the fundamental mechanisms of accessibility, affordability and availability of nutritious food items for those in the lowest socio-economic strata. PMID- 27198519 TI - Dopamine and the Adolescent Brain: Do Errors in Prediction Make the Difference? PMID- 27198520 TI - A NAc for Spinal Adjustments After Cocaine or Stress. PMID- 27198521 TI - A Role for Lactate in the Consolidation of Drug-Related Associative Memories. PMID- 27198522 TI - Dopamine and Obesity: A Path for Translation? PMID- 27198524 TI - Impact of Arachidonic Acid and the Leukotriene Signaling Pathway on Vasculogenesis of Mouse Embryonic Stem Cells. AB - Embryonic stem (ES) cells can differentiate into various kinds of cells, such as endothelial and hematopoietic cells. In addition, some evidence suggests that inflammatory mediators such as leukotrienes (LTs), which include the 5 lipoxygenase (LOX) family, can regulate endothelial cell differentiation. In the present study, the eicosanoid precursor arachidonic acid (AA) stimulated vasculogenesis of ES cells by increasing the number of fetal liver kinase-1+ vascular progenitor cells as well as vascular structures positive for platelet endothelial cell adhesion protein-1 and vascular endothelial cadherin. The stimulation of vasculogenesis and expression of the rate-limiting enzyme in the LT signaling pathway, 5-LOX-activating protein (FLAP), was blunted upon treatment with the FLAP inhibitors AM643 and REV5901. Vasculogenesis was significantly restored upon exogenous addition of LTs. Downstream of FLAP, the LTB4 receptor (BLT1) blocker U75302, the BLT2 receptor blocker LY255283 as well as the cysteinyl LT blocker BAY-u9773 inhibited vasculogenesis of ES cells. AA treatment of differentiating ES cells increased reactive oxygen species (ROS) generation, which was not affected upon either FLAP or cyclooxygenase-2 inhibition. Prevention of ROS generation by either the free radical scavengers vitamin E and N-(2-mercaptopropionyl)glycine or the NADPH oxidase inhibitor VAS2870 downregulated vasculogenesis of ES cells and blunted the provasculogenic effect of AA. In summary, our data demonstrate that proinflammatory AA stimulates vasculogenesis of ES cells via the LT pathway by mechanisms involving ROS generation. PMID- 27198523 TI - Efficacy and Safety of Induction Chemotherapy in Esophageal Cancer with Airway Involvement. AB - PURPOSE: Esophageal cancer with tracheobronchial involvement (TBI) has a poor prognosis. Radical therapy carries the risk of inducing tracheoesophageal fistula (TEF) and treatment-related mortality. Induction chemotherapy followed by reassessment for radical therapy may decrease morbidity and improve outcome. METHODS: This is a retrospective analysis of esophageal cancer patients with TBI who received induction chemotherapy. Airway involvement was defined as bronchoscopic appearance of a bulge into the lumen, restricted or immobile mucosa, frank infiltration, TEF, or stridor, which was clinically due to airway obstruction from the esophageal lesion. RESULTS: Eighty-three patients were included over 5 years; 97.6 % had squamous histology. All patients received taxane and platinum combination induction chemotherapy; 90.5 % of patients received chemotherapy without dose delays, and 77.8 % patients did not require a dose reduction or modification. The 31.7 % patients had a clinically significant >=grade 3 toxicity. The objective response rate was 67 % among the patients who underwent restaging scans following induction chemotherapy; 79.5 % of the patients could receive radical intent therapy, either concurrent chemoradiotherapy, or radiation alone, or surgery in one patient. The TEF complication rate was 6 % during the course of therapy. At a median follow-up of 28 months in surviving patients, the estimated median PFS was 8 months (95 % CI 5.5-10.5) and the estimated median OS was 17 months (95 % CI 5.6-28.4). Patients who received radical therapy had a significantly better PFS and OS, p = 0.000. CONCLUSIONS: Induction chemotherapy may improve the outcome of patients with esophageal cancer involving the airway and may help select patients for curative treatment and lower the risk of TEF development. PMID- 27198526 TI - Infants Operated on for Necrotizing Enterocolitis: Towards Evidence-Based Pain Guidelines. AB - BACKGROUND: Necrotizing enterocolitis (NEC) is known as an extremely painful childhood condition. OBJECTIVES: The objective of this study was to explore pain management around NEC-related surgery in our neonatal intensive care unit (NICU) from a chart review of prospectively collected data on 60 operated NEC patients admitted between 2008 and 2013 with a median (IQR) gestational age of 28.3 (25.5 31.6) weeks. METHODS: Pain medication data and pain scores (i.e. COMFORTneo and Numerical Rating Scale pain and distress scores) from 72 h before until 72 h after surgery were collected. RESULTS: Preoperatively, 95% of the patients received morphine versus 100% postoperatively, with a median dosage of 10.0 (IQR 9.7-14.5) and 16.9 (IQR 10.1-20.0) MUg/kg/h, respectively. Postoperatively, 28 patients (46.7%) received additional fentanyl intermittently and 14 (23.3%) received midazolam, which was part of palliative treatment for 6 patients (42.9%). In patients receiving pain medication, median COMFORTneo scores were 10 (IQR 10-11) preoperatively and 11 (10-12) postoperatively. The pain scores were comparable with those of other patients admitted to the NICU in the same time period. CONCLUSIONS: Continuous morphine of 10 MUg/kg/h preoperatively, with an increase to 15 MUg/kg/h postoperatively, seems to constitute a good starting dose for further individualized pain management guided by pain scores. PMID- 27198525 TI - Surgical Removal of Embolized Ventricular Septal Occluder Device. AB - Ventricular septal defect (VSD) with valvar pulmonary stenosis (PS) is a combination of cardiac defects for which treatment by means of percutaneous catheter-directed intervention is sometimes considered. Septal occluder device embolization is a rare but potentially dreadful complication. Adequate precautions are of great importance, as operator-related and anatomical factors can contribute to the risk of device embolization. In this report, we present a case of a five-year-old patient with a perimembranous VSD and valvar PS with infundibular muscle hypertrophy. The PS was treated with balloon pulmonary valvotomy, and the VSD was closed with a catheter-directed duct occluder device. Soon after deployment, the device embolized to the aortic arch, possibly as a result of the single disc device being "milked" out of VSD by dynamic contractions of hypertrophied muscle in the right ventricular outflow tract. The embolized device was successfully retrieved and removed using cardiopulmonary bypass and a period of circulatory arrest. PMID- 27198527 TI - Editorial: Patient safety in mental health services: Understanding the impact of emotional harm. PMID- 27198529 TI - The Role of Breastfeeding in the Prevention of Childhood Malnutrition. AB - Breastfeeding has an important role in the prevention of different forms of childhood malnutrition, including wasting, stunting, over- and underweight and micronutrient deficiencies. This chapter reviews research that demonstrates how improved breastfeeding rates have the potential to improve childhood nutrition, with associated impacts on infectious and noninfectious disease prevention. The unique composition of breastmilk, the importance of breastfeeding in infectious disease prevention, the iron status of breastfed infants, and breastfeeding's protective effect on overweight and obesity are discussed based on currently available research. Early and tailored dietary counseling is needed to improve maternal diets, which can affect the nutritional status of breastmilk. Promotion and support of breastfeeding are important to prevent childhood morbidity and mortality. A review of the literature reveals key factors shown to be effective in improving breastfeeding rates, especially including legislation to control the marketing of breastmilk substitutes. In conclusion, breastfeeding is shown to be the best natural resource to improve childhood nutrition throughout the world. PMID- 27198528 TI - Comparative protein profiles of Butea superba tubers under seasonal changes. AB - Seasonal changes are major factors affecting environmental conditions which induce multiple stresses in plants, leading to changes in protein relative abundance in the complex cellular plant metabolic pathways. Proteomics was applied to study variations in proteome composition of Butea. superba tubers during winter, summer and rainy season throughout the year using two-dimensional polyacrylamide gel electrophoresis coupled with a nanoflow liquid chromatography coupled to electrospray ionization quadrupole-time-of-flight tandem mass spectrometry. A total of 191 protein spots were identified and also classified into 12 functional groups. The majority of these were mainly involved in carbohydrate and energy metabolism (30.37 %) and defense and stress (18.32 %). The results exhibited the highest numbers of identified proteins in winter harvested samples. Forty-five differential proteins were found in different seasons, involving important metabolic pathways. Further analysis indicated that changes in the protein levels were due mainly to temperature stress during summer and to water stress during winter, which affected cellular structure, photosynthesis, signal transduction and homeostasis, amino-acid biosynthesis, protein destination and storage, protein biosynthesis and stimulated defense and stress mechanisms involving glycolytic enzymes and relative oxygen species catabolizing enzymes. The proteins with differential relative abundances might induce an altered physiological status within plant tubers for survival. The work provided new insights into the better understanding of the molecular basis of plant proteomes and stress tolerance mechanisms, especially during seasonal changes. The finding suggested proteins that might potentially be used as protein markers in differing seasons in other plants and aid in selecting B. superba tubers with the most suitable medicinal properties in the future. PMID- 27198530 TI - Objectifying the level of incomplete revascularization by the residual SYNTAX score and evaluating its impact on the one-year outcome of percutaneous coronary intervention in patients with multi-vessel disease. AB - BACKGROUND: Previous studies reported conflicting results regarding the impact of incomplete revascularization on the outcome of percutaneous coronary intervention (PCI). We evaluated the association between residual SYNTAX score (RSS) as a quantitative measure of incomplete revascularization and one-year outcome of patients with native multi-vessel disease undergoing PCI. METHODS: A total of 760 patients (mean age=59.14+/-10.36years, 70.4% males) who underwent successful PCI with the incomplete revascularization strategy between September 2008 and March 2010 were included. The RSS was used to quantify the extent and complexity of residual coronary stenosis following PCI. Multivariable analysis was used to evaluate the impact of RSS on one-year major adverse cardiac events (MACE) including death, myocardial infarction, and revascularization. RESULTS: Overall incidence of one-year MACE was 4.74%. Using ROC curve analysis a cut-off of >5 for baseline RSS had a significant association with occurrence of 12-month MACE (area under the curve=0.769; P value<0.001, sensitivity =75% and specificity=72%). Unadjusted effect of RSS>5 on 12months MACE showed a hazard ratio of 7.34 (p value<0.001). By multivariable analysis, effect of the RSS>5 on 12months MACE was adjusted for potential confounders. After adjustment to clinical SYNTAX score as the sole confounder, RSS>5 remained a strong associate with 12months MACE and its effect outweighed that of before adjustment (hazard ratio=8.03, p value<0.001). CONCLUSIONS: The RSS is a quantified measure of the complexity of residual coronary stenoses, and RSS>5 could be able to discriminate patients with an increased risk of one-year MACE. PMID- 27198531 TI - Pediatric perioperative adverse events requiring rapid response: a retrospective case-control study. AB - BACKGROUND: Perioperative pediatric adverse events have been challenging to study within and across institutions due to varying definitions, low event rates, and incomplete capture. AIM: The aim of this study was to determine perioperative adverse event prevalence and to evaluate associated case characteristics and potential contributing factors at an academic pediatric quaternary-care center. METHODS: At the Children's Hospital of Philadelphia (CHOP), perioperative adverse events requiring rapid response assistance are termed Anesthesia Now (AN!) events. They have been accurately captured and entered into a quality improvement database since 2010. Adverse events involving open heart and cardiac catheterization cases are managed separately and not included in this database. We conducted a retrospective case-control study utilizing Compurecord (Phillips Healthcare, Andover, MA, USA), EPIC (EPIC, Verona, WI, USA), and Chartmaxx (MedPlus, Mason, OH, USA) systems matching AN! event cases to noncardiac controls (1 : 2) based on surgical date. RESULTS: From April 16, 2010 to September 25, 2012, we documented 213 AN! events in the noncardiac perioperative complex and remote sites at our main hospital. AN! prevalence was 0.0043 (1 : 234) with a 95% confidence interval (CI) (0.0037, 0.0049). Respiratory events, primarily laryngospasm, were most common followed by events of cardiovascular etiology. Median age was lower in the AN! group than in controls, 2.86 years (interquartile range 0.94, 10.1) vs 6.20 (2.85, 13.1), P < 0.0001. Odds ratios (with 95% CI) for age, 0.969 (0.941, 0.997); American Society of Anesthesiologists physical status, 1.67 (1.32, 2.12); multiple (>=2) services, 2.27 (1.13, 4.55); nonoperating room vs operating room location, 0.240 (0.133, 0.431); and attending anesthesiologist's experience, 0.976 (0.959, 0.992) were all significant. CONCLUSIONS: Decreased age, increased comorbidities, multiple (vs single) surgical services, operating room (vs nonoperating room) location, and decreased staff experience were associated with increased risk of AN! events, which were predominantly respiratory in origin. PMID- 27198532 TI - Let's Move Together. AB - BACKGROUND: Due to shared health behaviors and disease risk, families may be more effective targets for health promotion. This study assessed whether providing family health history (FHH)-based risk information for heart disease and diabetes affected encouragement to engage in physical activity (PA) and healthy weight (HW) maintenance and co-engagement in physical activity among 320 Mexican-origin parents and their 1,081 children. METHOD: At baseline and 10 months, parents indicated who they encouraged and who encouraged them to engage in PA/HW, and with whom they co-engaged in PA. Households were randomized to receive FHH-based assessments either by one or all adult household members. Primary analyses consisted of regression analyses using generalized estimating equations. RESULTS: At baseline, parents reported encouraging their child for both PA and HW in 37.6% of parent-child dyads and reported receiving children's encouragement for both in 12.1% of dyads. These increased to 56.8% and 17.5% at 10 months ( p < .001). Co engagement in PA increased from 11.4% to 15.7% ( p < .001), with younger children (30.4%) and mother-daughter dyads (26.8%) most likely to co-engage at 10 months. Providing FHH-based risk information to all adult household members (vs. one) was associated with increased parent-to-child encouragement of PA/HW ( p = .011) at 10 months but not child-to-parent encouragement. New encouragement from parent-to child ( p = .048) and from child-to-parent ( p = .003) predicted new 10-month PA co-engagement. DISCUSSION: Providing FHH information on a household level can promote parental encouragement for PA/HW, which can promote greater parent-child co-engagement in PA. In this high-risk population with a cultural emphasis on family ties, using FHH-based risk information for all adult household members may be a promising avenue to promote PA. PMID- 27198533 TI - The FAV-S Pilot Study. AB - The 2012 FAV-S pilot study was developed as a dietary intervention program for low-income Somali mothers grounded in the health belief model. The intervention was geared toward increasing fruit and vegetable intake among participants' children. The purpose of this analysis was to determine the impact of the FAV-S program on participants' (1) self-efficacy in ability to serve more fruits and vegetables, (2) knowledge and beliefs about healthy eating, and (3) perceived barriers to accessing healthy foods. Furthermore, this study assessed change in fruit and vegetable intake among participants and their children. The intervention consisted of two small group education sessions addressing nutrition, serving size, and label reading; a cooking session incorporating fruits and vegetables into traditional Somali dishes; and a grocery store session demonstrating best purchasing practices. Self-efficacy, knowledge and beliefs, and perceived barriers were assessed via surveys administered verbally in Somali pre- and postintervention. Paired t tests were used to compare pre- and postintervention survey responses. Twenty-five women participated in the pilot study; mean age was 43.6 years ( SD = 12.4). Self-efficacy significantly increased among participants postintervention ( p = .01), though there were no significant changes in knowledge and beliefs or perceived barriers. Following intervention, daily servings of fruits and vegetables significantly increased among both women and children ( p = .01 to p < .01). Findings suggest that a multistage, culturally tailored, approach is effective at increasing self efficacy and fruit and vegetable intake in the Somali community. Continued and expanded research is needed to further develop culturally focused dietary interventions. PMID- 27198534 TI - Obesity Prevention in Early Child Care Settings. AB - BACKGROUND: Long-term evaluation studies reveal that high-quality early care and education (ECE) programs that include a lifestyle component predict later adult health outcomes. The purpose of this article is to characterize the nutrition and physical activity (PA) practices, including implementation difficulty and barriers, of licensed center- and family home-based ECE programs serving 2- to 5 year-old children in Minnesota (MN) and Wisconsin (WI). METHOD: A stratified random sampling procedure was used to select representative cross sections of licensed ECE providers in MN and WI. A total of 2,000 providers (1,000 center based, 1,000 family home-based) were randomly selected and invited to respond to a 97-item survey with questions representing (1) nutrition and PA practices, (2) barriers to meeting nutrition and PA best practices, and (3) written and implemented nutrition and PA policies. Summated scales were constructed for nutrition-related (range 0-15; Cronbach's alpha = .86) and for PA-related best practices (range 0-10; Cronbach's alpha = .82). RESULTS: A total of 823 providers returned surveys between August 2010 and March 2011, resulting in a 44% bistate participation rate. Across all programs an average ( SD) of 7.0 (4.1) nutrition best practices were already implemented. Center-based providers reported on average 0.8 additional nutrition best practice (7.4 vs. 6.6, p = .01). Across all programs an average ( SD) of 5.2 (3.1) PA best practices were already implemented. Center-based providers reported on average one more PA best practice (5.3 vs. 4.3, p < .01). The cost of healthy food and the weather were identified as barriers by 80% of providers, regardless of program type. PMID- 27198535 TI - Outcome Evaluation of Family Eats. AB - This article presents the results of a randomized clinical trial evaluating the eight-session Family Eats web-based intervention promoting healthy home food environments for African American families. African American families ( n = 126) with 8- to 12-year-old children completed online baseline questionnaires and were randomized into intervention or control groups. Data collection occurred at baseline, immediately postintervention (Post 1), and 4 months later (Post 2), for parents and children, separately. There were two group by time intervention effects: Control group parents reported a significantly greater frequency of drinking 100% fruit juice at Post 1 compared with intervention group parents. Parent menu planning skills were significantly higher at Post 2 for the intervention group compared with the control group. Significant positive changes overtime were noted for both groups for home fruit/vegetable availability, food preparation practices, and healthy restaurant selection. Intervention group children reported a significant increase in home juice availability at Post 1 compared with the control group; home fruit availability improved for both groups. There was no difference in log on rates by group: 84% and 86% for those who completed Post 1 and Post 2 measurements, respectively. Sixty-four participants completed the evaluation survey: 17 control (50%) and 47 intervention (51%) participants. All participants reported liking the program components; all but one gave it an A or B grade. An Internet-delivered nutrition intervention for families was successful in achieving change in some mediating variables, with good log on rates. Future research with Family Eats should include larger sample sizes, with longer follow-up and a more objective measure of diet. PMID- 27198536 TI - Development of a Brief Pre-Implementation Screening Tool to Identify Teachers Who Are at Risk for Not Implementing Intervention Curriculum and High-Implementing Teachers. AB - Few questionnaires have been developed to screen for potentially poor implementers of school-based interventions. This study combines teacher characteristics, perceptions, and teaching/training experiences to develop a short screening tool that can identify potential "low-performing" or "high performing" teachers pre-implementation. Data were gathered from 208 teachers and 4,411 students who participated in the national implementation of an evidence based HIV intervention in The Bahamas. Sensitivity and specificity were evaluated for the detection of "low-performing" and "high-performing" teachers. The validity of the screening tool was assessed using receiver operating characteristics analysis. The School Pre-implementation Screening Tool consists of seven predictive factors: duration as teacher, working site, attendance at training workshops, training in interactive teaching, perceived importance of the intervention, comfort in teaching the curriculum, and program priority. The sensitivity and specificity were 74% and 57% in identifying "low-performing" teachers and 81% and 65% with "high-performing" teachers. The screening tool demonstrated an acceptable/good validity (area under the receiver operating characteristics curve was 0.68 for "low-performing teachers" and 0.78 for "high performing" teachers). Our brief screening tool can facilitate teacher training and recruitment of engaged teachers in implementation of school-based interventions. PMID- 27198538 TI - In defense of a supernatural foundation to morality: reply to Shermer. AB - In my original paper, I claimed that our moral obligations are real, objective, and grounded in the supernatural. In particular, I endorsed the claim that God's will is the basis or source of our moral obligations, where "God" is to be understood as the theistic being who is omnibenevolent, omniscient, and omnipotent, who created the universe, and who is still actively involved in the universe after creating it. In his critical article, Michael Shermer has raised a number of important challenges to my view. Here I try to defend the position and respond to at least his most serious objections. PMID- 27198537 TI - Knockout of ho-1 protects the striatum from ferrous iron-induced injury in a male specific manner in mice. AB - Men have worse survival than premenopausal women after intracerebral hemorrhage (ICH). After ICH, overproduction of iron associated with induction of heme oxygenase-1 (HO-1) in brain was observed. Rodent ICH model using ferrous citrate (FC)-infusion into the striatum to simulate iron overload, showed a higher degree of injury severity in males than in females. However, the participation of HO-1 in sex-differences of iron-induced brain injury remains unknown. The present results showed a higher level of HO-1 expression associated with more severe injury in males compared with females after FC-infusion. Estradiol (E2) contributed to lower levels of FC-induced HO-1 expression in females compared with males. Heterozygote ho-1 KO decreased the levels of FC-induced injury severity, histological lesions, behavioral deficits, autophagy and autophagic cell death in the striatum of males but not in females. Moreover, ho-1 deficiency enhanced the neuroprotection by E2 only in males. These results suggested that over induction of HO-1 plays a harmful role in FC-induced brain injury in a male specific manner. Suppression of HO-1 combined with E2 exhibits a synergistic effect on neuroprotection against FC-induced striatal injury in males. These findings open up the prospect for male-specific neuroprotection targeting HO-1 suppression for patients suffering from striatal iron overload. PMID- 27198539 TI - Clinical assessment of enamel wear caused by monolithic zirconia crowns. AB - The purpose of this study was to measure enamel wear caused by antagonistic monolithic zirconia crowns and to compare this with enamel wear caused by contralateral natural antagonists. Twenty monolithic zirconia full molar crowns were placed in 20 patients. Patients with high activity of the masseter muscle at night (bruxism) were excluded. For analysis of wear, vinylpolysiloxane impressions were prepared after crown incorporation and at 6-, 12-, and 24-month follow-up. Wear of the occlusal contact areas of the crowns, of their natural antagonists, and of two contralateral natural antagonists (control teeth) was measured by use of plaster replicas and a 3D laser-scanning device. Differences of wear between the zirconia crown antagonists and the control teeth were investigated by means of two-sided paired Student's t-tests and linear regression analysis. After 2 years, mean vertical loss was 46 MUm for enamel opposed to zirconia, 19-26 MUm for contralateral control teeth and 14 MUm for zirconia crowns. Maximum vertical loss was 151 MUm for enamel opposed to zirconia, 75-115 MUm for control teeth and 60 MUm for zirconia crowns. Statistical analysis revealed significant differences between wear of enamel by zirconia-opposed teeth and by control teeth. Gender, which significantly affected wear, was identified as a possible confounder. Monolithic zirconia crowns generated more wear of opposed enamel than did natural teeth. Because of the greater wear caused by other dental ceramics, the use of monolithic zirconia crowns may be justified. PMID- 27198540 TI - One in three female clinician-researchers reports sexual harassment, US survey finds. PMID- 27198541 TI - Hypoalbuminaemia at admission predicts the poor outcomes in critically ill children. AB - BACKGROUND: Hypoalbuminaemia at admission is a common finding in patients admitted to the Paediatric Intensive Care Unit (PICU) and it is thought that this may predict morbidity and mortality. METHODS: A retrospective study was conducted in the tertiary hospital. The medical records of critically ill children were reviewed. The data were analyzed for the prevalence of hypoalbuminaemia and outcomes. RESULTS: Two hundred and two patients were included in the analysis. The incidence of hypoalbuminaemia at admission was 57.9%. These patients had a mortality rate 4 times greater (adjusted odds ratio 3.8; 95% CI: 1.4-10.0), a longer length of PICU stay (8.6 vs. 6.7 days, P = 0.04) and a longer period on a ventilator (5.9 vs. 3.9 days, P = 0.04) than patients with normal albumin levels. CONCLUSIONS: Hypoalbuminaemia at admission was a predictive factor of poor outcome in critically ill children. It is associated with a higher mortality, a longer length of stay in the PICU, as well as longer ventilator use. PMID- 27198543 TI - Erratum: A pharmacological inhibitor of NLRP3 inflammasome prevents non-alcoholic fatty liver disease in a mouse model induced by high fat diet. PMID- 27198542 TI - Exercise as an alternative treatment for chronic insomnia (PEDro synthesis). PMID- 27198544 TI - Persistent organic pollutants in tissues of the white-blooded Antarctic fish Champsocephalus gunnari and Chaenocephalus aceratus. AB - The global occurrence of persistent organic pollutants (POPs) continuously contributes to their accumulation also in remote areas such as the Antarctic Ocean. Antarctic fish, which hold high trophic positions but appear to possess low endogenous elimination rates for chemicals, are expected to bioaccumulate POPs with rising anthropogenic pollution. Using a chemical-analytical method, we measured concentrations of PCBs, PBDEs, HCBs, HCH and DDTs and determined toxic equivalents (TEQs) and bioanalytical equivalents (BEQs) in muscle and ovaries of Antarctic icefish caught in the Southern Ocean around Elephant Island. We used two species with different feeding habits and trophic web positions: the planktivorous Champsocephalus gunnari and the piscivorous Chaenocephalus aceratus. Our results revealed higher contaminant levels in ovary than in muscle tissues of both species. Most analytes concentrations and the TEQs (0.2-0.5) and BEQs (0.2) were lower as in temperate species. Comparison with literature data points to higher PCB (20-22 ng g(-1) lipid weight (lw)) and DDT (7-19.5 ng g(-1) lw) concentrations than those measured in icefish in the 90's. For the other contaminants, we could not identify temporal trends. We found a higher bioaccumulation of contaminants, particularly HCB and DDTs, in C. aceratus (6.2 & 19.5 ng g(-1) lw, respectively) than in C. gunnari (3.8 & 7.0 ng g(-1) lw, respectively). However, there was no general species-specific accumulation pattern of the different toxicant classes between the two icefish. Thus, the expected link between contaminant burdens of C. aceratus and C. gunnari and their ecological traits was only weakly supported for these species. PMID- 27198545 TI - Poor tuberculosis treatment outcomes in Southern Mozambique (2011-2012). AB - BACKGROUND: In Mozambique, there is limited data regarding the monitoring of Tuberculosis (TB) treatment results and determinants of adverse outcomes under routine surveillance conditions. The objectives of this study were to evaluate treatment outcomes among TB patients, analyze factors associated with a fatal outcome and determine the proportion of deaths attributable to TB in the district of Manhica, Southern Mozambique. METHODS: This is a retrospective observational study based on TB patients diagnosed in the period 2011-2012. We used three different data sources: a) TB related variables collected by the National TB Control Program in the district of Manhica for all TB cases starting treatment in the period 2011-2012. b) Population estimates for the district were obtained through the Mozambican National Statistics Institute. c) Deaths and other relevant demographic variables were collected from the Health and Demographic Surveillance System at Manhica Health Research Center. WHO guidelines were used to define TB cases and treatment outcomes. RESULTS: Of the 1957 cases starting TB treatment in the period 2011-2012, 294 patients (15.1 %) died during anti tuberculous treatment. Ten per cent of patients defaulted treatment. The proportion of patients considered to have treatment failure was 1.1 %. HIV infection (OR 2.73; 95 % CI: 1.70-4.38), being male (OR: 1.39; 95 % CI 1.01-1.91) and lack of laboratory confirmation (OR: 1.54; 95 % CI 1.12-2.13) were associated with dying during the course of TB treatment (p value <0.05). The contribution of TB to the overall death burden of the district for natural reasons was 6.5 % (95 % CI: 5.5-7.6), higher for males than for females (7.8 %; 95 % CI: 6.1-9.5 versus 5.4 %; 95 % CI: 4.1-6.8 respectively). The age group within which TB was responsible for the highest proportion of deaths was 30-34 among males and 20-24 among females (20 % of all deaths in both cases). CONCLUSION: This study shows a very high proportion of fatal outcomes among TB cases starting treatment. There is a high contribution of TB to the overall causes of mortality. These results call for action in order to improve TB (and TB/HIV) management and thus treatment outcomes of TB patients. PMID- 27198546 TI - Consumer reporting of adverse drug reactions: Systems that allow patients to report side effects of the drugs they are taking have yielded valuable information for improving drugs safety and health care. PMID- 27198547 TI - Erratum to: 'Mediterranean versus vegetarian diet for cardiovascular disease prevention (the CARDIVEG study): study protocol for a randomized controlled trial'. PMID- 27198550 TI - Prediction of the electronic structure of single-walled black phosphorus nanotubes. AB - Due to its high carrier mobility and tunable bandgap, phosphorene has been the subject of immense interest recently. Herein, we show using density functional theory based calculations that black phosphorus (BP) nanotubes are achievable. Moreover, the electronic properties of BP nanotubes are explored. In contrast to their monolayer and bulk counterparts, most BP nanotubes possess indirect band gaps. In addition, strong anisotropic electronic behaviors are observed between zigzag and armchair nanotubes. Semiconducting to semi-metallic transition occurs only for zigzag tubes when its diameter shrinks to ~1.5 nm. This difference is strongly related to the bond bending after the formation of the nanotubes which governs the s-p hybridization, as well as electron distribution in different p orbitals and this eventually determines the electronic structure of BP nanotubes. PMID- 27198548 TI - Surgical flow disturbances in dedicated minimally invasive surgery suites: an observational study to assess its supposed superiority over conventional suites. AB - BACKGROUND: Minimally invasive surgery (MIS) is frequently compromised by surgical flow disturbances due to technology- and equipment-related failures. Compared with MIS in a conventional cart-based OR, performing MIS in a dedicated integrated operating room (OR) is supposed to be beneficial to patient safety. The aim of this study was to compare a conventional OR with an integrated OR with regard to the incidence and effect of equipment-related surgical flow disturbances during an advanced laparoscopic gynecological procedure [laparoscopic hysterectomy (LH)]. METHODS: Using video recording, 40 LHs performed between November 2010 and April 2012 (20 in a conventional cart-based OR and 20 in an integrated OR) were analyzed by two different observers. Outcome measures were the number, duration and effect (on a seven-point ordinal scale) of the surgical flow disturbances (e.g., malfunctioning, intraoperative repositioning, setup device). RESULTS: A total of 103 h and 45 min was observed. The interobserver agreement was high (kappa .85, p < .001). Procedure time was not significantly different (NS) [conventional OR vs. integrated OR, minutes +/- standard deviation (SD), mean 161 +/- 27 vs. 150 +/- 34]. A total of 1651 surgical flow disturbances were observed (mean +/- SD per procedure 40.8 +/- 19.4 vs. 41.8 +/- 15.9, NS). The mean number of surgical flow disturbances per procedure with regard to equipment was 6.3 +/- 3.7 versus 8.5 +/- 4.0, NS. No clinically relevant differences in the mean effect of these disturbances on the surgical flow between the two OR setups were observed. CONCLUSIONS: Performing LH in an integrated OR did not reduce the number of surgical flow disturbances nor the effect of these disturbances. Furthermore, in the integrated OR, repositioning of the monitors was a frequent and time-consuming source of disturbance. In order to maintain the high standard of surgical safety, the entire surgical team has to be aware that by performing surgery in an integrated OR different potential source for disruption arise. PMID- 27198549 TI - Surgical advantages of reduced-port laparoscopic gastrectomy in gastric cancer. AB - BACKGROUND: Although a few studies have reported the use of reduced-port laparoscopic gastrectomy (RPG) in gastric cancer patients, the feasibility of routinely using this technique remains unclear. It is therefore important to evaluate the surgical advantages of this technique in this patient group. METHODS: Between August 2010 and July 2015, 165 patients underwent RPGs at our hospital, performed by a single surgeon. Of these patients, 88 underwent reduced port laparoscopic distal gastrectomy (RPLDG) and 77 underwent reduced-port laparoscopic total gastrectomy (RPLTG). In addition to short-term surgical outcomes after RPG, survival times and the surgical learning curve were also evaluated. RESULTS: Blood losses during lymph node dissection in the RPLDG and RPLTG groups were not significantly different (p = 0.160). Conversion to open surgery was necessary in only two patients. Postoperative morbidities were observed in 14.8 % of the RPLDG group and 14.3 % of the RPLTG group, but there were no deaths. Most patients expressed high cosmetic satisfaction in both groups. In the RPLDG group, operation time during reconstruction decreased over the first 50 cases and then plateaued, as the surgeon's experience of the technique increased. In contrast, in the RPLTG group, operation times dropped with surgical experience for both lymph node dissection, plateauing after 40 cases, and for reconstruction, plateauing after 30 cases. Only three patients died of gastric cancer in the follow-up period and three patients died of other diseases. Five-year overall survival and 5-year disease-specific survival were 95.6 and 98.0 %, respectively. CONCLUSIONS: We have shown that reduced-port gastrectomy (RPG) could be an acceptable and satisfactory procedure for treating gastric cancer for an experienced laparoscopic gastric surgeon who has sufficient previous experience of conventional laparoscopic gastrectomies. PMID- 27198551 TI - European Society of Radiology (ESR) and American College of Radiology (ACR) report of the 2015 global summit on radiological quality and safety. AB - The American College of Radiology (ACR) and the European Society of Radiology (ESR) held the second joint Global Summit on Radiological Quality and Safety on October 10-11, 2015 in Barcelona. The programme addressed the issues of safety, professional performance, practice improvement and customer service. Participants came from national and international radiological societies; partner medical societies; global organisations such as the International Atomic Energy Agency and the World Health Organisation; and patient advocacy groups. The objective was to exchange ideas and develop common strategies to improve and harmonise quality and safety in radiology on a global level. Participants debated and proposed improvement initiatives at the conclusion of the meeting. MAIN MESSAGES: * Radiologists must adapt to demonstrate their value to the healthcare system. * Integration of quality and safety policies is crucial for our profession. * Excellent patient care includes good communication and direct involvement in clinical problem solving. * Culture is shifting towards clinical decision support tools for appropriate use of imaging. * "Big data" is a great opportunity for radiologists to improve the quality of patient care. PMID- 27198552 TI - Combination of carmustine and selenite effectively inhibits tumor growth by targeting androgen receptor, androgen receptor-variants, and Akt in preclinical models: New hope for patients with castration resistant prostate cancer. AB - Despite established androgen receptor (AR) antagonists, AR/AR-variants signaling remain a major obstacle for the successful treatment of castration resistant prostate cancer (CRPC). In addition, CRPC cells adapt to survive via AR independent pathways to escape next generation therapies. Therefore, there is an urgent need for drugs that can target these signaling pathways in CRPC. In this study, we sought to determine whether carmustine and selenite in combination could induce apoptosis and inhibit growth of CRPC in-vitro and in-vivo. CRPC (22Rv1, VCaP, and PC-3) cell lines in culture and xenograft mouse were used. Combination of carmustine and selenite treatment significantly increased reactive oxygen species, apoptosis and growth inhibition in CRPC cells with down regulation of anti-apoptotic (Bcl-2 and Mcl-1) and proliferative proteins (c-Myc and cyclin-D1). This effect was associated with complete reduction of AR/AR variants, AR-V7, PSA and significant induction of p27Kip1. Combination treatment substantially abolished phospho-Akt, phospho-GSK-3beta, and anchorage-independent growth in AR-positive and AR-negative cells. Consistent with in-vitro results, combination treatment effectively induced apoptosis and completely inhibited xenograft tumor growth and markedly reduced AR/AR-variants, AR-V7, PSA, and Bcl-2 in xenograft tumors without causing genotoxicity in host mice. Individual agent treatment showed only partial effect. The combination treatment showed a significant synergistic effect. The present study is the first to demonstrate that the combination of carmustine and selenite treatment completely suppressed CRPC tumor growth by reducing AR/AR-variants and Akt signaling. Our findings suggest that the combination of carmustine and selenite could constitute a promising next-generation therapy for successful treatment of patients with CRPC. PMID- 27198553 TI - The Cannabis Policy Framework by the Centre for Addiction and Mental Health: A proposal for a public health approach to cannabis policy in Canada. PMID- 27198554 TI - Collaborative transition to a methadone formulation change in British Columbia, Canada. PMID- 27198556 TI - Alcohol-free spirits as novel alcohol placebo - A viable approach to reduce alcohol-related harms? PMID- 27198555 TI - Income inequality, drug-related arrests, and the health of people who inject drugs: Reflections on seventeen years of research. AB - This paper reviews and then discusses selected findings from a seventeen year study about the population prevalence of people who inject drugs (PWID) and of HIV prevalence and mortality among PWID in 96 large US metropolitan areas. Unlike most research, this study was conducted with the metropolitan area as the level of analysis. It found that metropolitan area measures of income inequality and of structural racism predicted all of these outcomes, and that rates of arrest for heroin and/or cocaine predicted HIV prevalence and mortality but did not predict changes in PWID population prevalence. Income inequality and measures of structural racism were associated with hard drug arrests or other properties of policing. These findings, whose limitations and implications for further research are discussed, suggest that efforts to respond to HIV and to drug injection should include supra-individual efforts to reduce both income inequality and racism. At a time when major social movements in many countries are trying to reduce inequality, racism and oppression (including reforming drug laws), these macro-social issues in public health should be both addressable and a priority in both research and action. PMID- 27198557 TI - Alcohol Interactive Toxicity Beliefs and ART Non-adherence Among HIV-Infected Current Drinkers in Mbarara, Uganda. AB - Interactive toxicity beliefs regarding mixing alcohol and antiretroviral therapy (ART) may influence ART adherence. HIV-infected patients in Uganda completed quarterly visits for 1 year, or one visit at 6 months, depending on study randomization. Past month ART non-adherence was less than daily or <100 % on a visual analog scale. Participants were asked if people who take alcohol should stop taking their medications (belief) and whether they occasionally stopped taking their medications in anticipation of drinking (behavior). Visits with self reported alcohol use and ART use for >=30 days were included. We used logistic regression to examine correlates of the interactive toxicity belief and behavior, and to determine associations with ART non-adherence. 134 participants contributed 258 study visits. The toxicity belief was endorsed at 24 %, the behavior at 15 %, and any non-adherence at 35 % of visits. In multivariable analysis, the odds of non-adherence were higher for those endorsing the toxicity behavior [adjusted odds ratio (AOR) 2.06; 95 % confidence interval (CI) 0.97 4.36] but not the toxicity belief (AOR 0.63; 95 % CI 0.32-1.26). Clear messaging about maintaining adherence, even if drinking, could benefit patients. PMID- 27198558 TI - Prohibiting direct medical care by US military personnel in foreign disaster relief: arguments from the Ebola disaster. PMID- 27198559 TI - Changes in Retinal Nerve Fiber Layer Thickness in Obstructive Sleep Apnea/Hypopnea Syndrome: A Meta-Analysis. AB - PURPOSE: To evaluate and compare changes in retinal nerve fiber layer (RNFL) thickness in patients with obstructive sleep apnea/hypopnea syndrome (OSAHS). METHODS: The Cochrane Library, Medline, and Embase were screened using our key words. Results were carefully reviewed to ensure that the included studies met the inclusion/exclusion criteria, and the quality of the studies was assessed using the Newcastle-Ottawa Scale. All included studies categorized patients with OSAHS into 3 groups (mild, moderate, and severe), and measured average and 4 quadrant (temporal, superior, nasal, and inferior) RNFL thickness. All studies included a healthy control group. The weighted mean differences and 95% confidence intervals were calculated for the continuous outcomes. RESULTS: Ten case-control studies were included in the meta-analysis, consisting of a total of 811 OSAHS group and 868 healthy eyes. A meta-analysis of the data showed that the average RNFL thicknesses in the mild, moderate, and severe OSAHS groups were significantly decreased compared to healthy controls. Additionally, RNFL thickness was significantly reduced in all but the temporal quadrant in the moderate and severe OSAHS groups when compared to healthy controls. CONCLUSIONS: On the basis of these results, we suggest that peripapillary RNFL thickness as measured by optical coherence tomography could be a useful tool to monitor and assess the severity of OSAHS in patients. Further studies are required in order to differentiate these RNFL changes from glaucomatous changes. This has not been properly examined in any of the studies we were able to identify. PMID- 27198561 TI - Trams, trains, planes and automobiles: logistics of conducting a statewide audit of medical records. AB - OBJECTIVE: This paper reports on the logistics of conducting a validation study of a routinely collected dataset against medical records at hospitals to inform planning of similar studies. METHOD: A stratified random sample of 15 hospitals and two homebirth practitioners was included. Site visits were arranged following consent. In addition to the validation of perinatal data, information was collected regarding logistics. RESULTS: Records at 14 metropolitan and rural hospitals up to 500 km from the research centre, and two homebirth practitioners, were audited. Obtaining consent to participate took between 5 days and 10 months. Auditors visited sites on 101 days, auditing 737 medical record pairs at 16 sites. Median audit time per record was 51.3 minutes; electronic records each took 36 minutes longer than paper. Travel time accounted for nearly one-quarter of audit time. CONCLUSIONS: Delays obtaining consents, long travel times and electronic records prolonged audit duration and expense. Employment of experts maximised use of available audit time. Conducting a validation study is a time consuming and expensive exercise; however, confidence in the accuracy of public health data is vital. IMPLICATIONS: Validation studies are unquestionably important. Three alternative strategies have been proposed to make future studies viable. PMID- 27198560 TI - Drug penetration and metabolism in 3D cell cultures treated in a 3D printed fluidic device: assessment of irinotecan via MALDI imaging mass spectrometry. AB - Realistic in vitro models are critical in the drug development process. In this study, a novel in vitro platform is employed to assess drug penetration and metabolism. This platform, which utilizes a 3D printed fluidic device, allows for dynamic dosing of three dimensional cell cultures, also known as spheroids. The penetration of the chemotherapeutic irinotecan into HCT 116 colon cancer spheroids was examined with MALDI imaging mass spectrometry (IMS). The active metabolite of irinotecan, SN-38, was also detected. After twenty-four hours of treatment, SN-38 was concentrated to the outside of the spheroid, a region of actively dividing cells. The irinotecan prodrug localization contrasted with SN 38 and was concentrated to the necrotic core of the spheroids, a region containing mostly dead and dying cells. These results demonstrate that this unique in vitro platform is an effective means to assess drug penetration and metabolism in 3D cell cultures. This innovative system can have a transformative impact on the preclinical evaluation of drug candidates due to its cost effectiveness and high throughput. PMID- 27198562 TI - Signatures of single quantum dots in graphene nanoribbons within the quantum Hall regime. AB - We report on the observation of periodic conductance oscillations near quantum Hall plateaus in suspended graphene nanoribbons. They are attributed to single quantum dots that are formed in the narrowest part of the ribbon, in the valleys and hills of a disorder potential. In a wide flake with two gates, a double-dot system's signature has been observed. Electrostatic confinement is enabled in single-layer graphene due to the gaps that are formed between the Landau levels, suggesting a way to create gate-defined quantum dots that can be accessed with quantum Hall edge states. PMID- 27198563 TI - How to Achieve Transparency in Public-Private Partnerships Engaged in Hunger and Malnutrition Reduction. AB - Multi-stakeholder partnerships are important facilitators of improving nutrition in developing countries to achieve the United Nations' Sustainable Development Goals. Often, the role of industry is challenged and questions are raised as to the ethics of involving for-profit companies in humanitarian projects. The Second International Conference on Nutrition placed great emphasis on the role of the private sector, including industry, in multi-stakeholder partnerships to reduce hunger and malnutrition. Governments have to establish regulatory frameworks and institutions to guarantee fair competition and invest in infrastructure that makes investments for private companies attractive, eventually leading to economic growth. Civil society organizations can contribute by delivering nutrition interventions and behavioral change-related communication to consumers, providing capacity, and holding governments and private sector organizations accountable. Industry provides technical support, innovation, and access to markets and the supply chain. The greatest progress and impact can be achieved if all stakeholders cooperate in multi-stakeholder partnerships aimed at improving nutrition, thereby strengthening local economies and reducing poverty and inequality. Successful examples of public-private partnerships exist, as well as examples in which these partnerships did not achieve mutually agreed objectives. The key requirements for productive alliances between industry and civil society organizations are the establishment of rules of engagement, transparency and mutual accountability. The Global Social Observatory performed a consultation on conflicts of interest related to the Scaling Up Nutrition movement and provided recommendations to prevent, identify, manage and monitor potential conflicts of interest. Multi-stakeholder partnerships can be successful models in improving nutrition if they meet societal demand with transparent decision-making and execution. Solutions to the issue of malnutrition are available. We have the resources and knowledge, and we must act as a global community in the immediate future. Transparency about the roles and contributions of each partner may be a key factor for successful cooperation in multi-stakeholder partnerships. PMID- 27198564 TI - Production of Glucaric Acid from Hemicellulose Substrate by Rosettasome Enzyme Assemblies. AB - Hemicellulose biomass is a complex polymer with many different chemical constituents that can be utilized as industrial feedstocks. These molecules can be released from the polymer and transformed into value-added chemicals through multistep enzymatic pathways. Some bacteria produce cellulosomes which are assemblies composed of lignocellulolytic enzymes tethered to a large protein scaffold. Rosettasomes are artificial engineered ring scaffolds designed to mimic the bacterial cellulosome. Both cellulosomes and rosettasomes have been shown to facilitate much higher rates of biomass hydrolysis compared to the same enzymes free in solution. We investigated whether tethering enzymes involved in both biomass hydrolysis and oxidative transformation to glucaric acid onto a rosettasome scaffold would result in an analogous production enhancement in a combined hydrolysis and bioconversion metabolic pathway. Three different enzymes were used to hydrolyze birchwood hemicellulose and convert the substituents to glucaric acid, a top-12 DOE value added chemical feedstock derived from biomass. It was demonstrated that colocalizing the three different enzymes to the synthetic scaffold resulted in up to 40 % higher levels of product compared to uncomplexed enzymes. PMID- 27198565 TI - The Modified Heparin-Binding L-Asparaginase of Wolinella succinogenes. AB - The modified asparaginase Was79 was derived from the recombinant wild-type L asparaginase of Wolinella succinogenes. The Was79 contains the amino acid substitutions V23Q and K24T responsible for the resistance to trypsinolysis and the N-terminal heparin-binding peptide KRKKKGKGLGKKR responsible for the binding to heparin and tumor K562 cells in vitro. When tested on a mouse model of Fischer lymphadenosis L5178Y, therapeutic efficacy of Was79 was significantly higher than that of reference enzymes at all single therapeutic doses used (125-8000 IU/kg). At Was79 single doses of 500-8000 IU/kg, the complete remission rate of 100 % was observed. The Was79 variant can be expressed intracellularly in E. coli as a less immunogenic formyl-methionine-free form at high per cell production levels. PMID- 27198566 TI - Proteomic Analysis in Esophageal Eosinophilia Reveals Differential Galectin-3 Expression and S-Nitrosylation. AB - BACKGROUND AIMS: Esophageal eosinophilia (EE) can be caused by gastroesophageal reflux disease (GERD), proton-pump inhibitor-responsive EE (PPI-REE) or eosinophilic esophagitis (EoE). This study quantified protein expression and S nitrosylation (SNO) post-translational modifications in EE to elucidate potential disease biomarkers. METHODS: Proximal and distal esophageal (DE) biopsy proteins in patients with EE and in controls were assayed for protein content and fluorescence-labeled with and without ascorbate treatment. Protein SNO was determined, and selected protein spots were identified by matrix-assisted laser desorption ionization time-of-flight/mass spectrometry. Western blot and ingenuity pathway analysis were performed. RESULTS: Ninety-one of 648 proteins showed differential expression. There were significantly altered levels of abundance for 11 proximal and 14 DE proteins. Hierarchal clustering revealed differential SNO in inflamed tissues, indicating reactive nitrogen/oxygen species involvement. Galectin-3 was upregulated in both proximal (p < 0.04) and distal (p < 0.004) esophageal EE biopsies compared to controls. In distal EE samples, galectin-3 was significantly S-nitrosylated (p < 0.004). Principal component analysis revealed sample group discrimination distally. CONCLUSION: Proteomic analysis in EE esophageal mucosa revealed a distinct abundance and nitrosylation profile, most prominently in distal biopsies. Galectin-3 was upregulated in expression and SNO, which may indicate its potential role in mucosal inflammation. These results call for more studies to be performed to investigate the role of galectin-3 in GERD, PPI-REE and EoE. PMID- 27198567 TI - Region of interest identification and diagnostic agreement in breast pathology. AB - A pathologist's accurate interpretation relies on identifying relevant histopathological features. Little is known about the precise relationship between feature identification and diagnostic decision making. We hypothesized that greater overlap between a pathologist's selected diagnostic region of interest (ROI) and a consensus derived ROI is associated with higher diagnostic accuracy. We developed breast biopsy test cases that included atypical ductal hyperplasia (n=80); ductal carcinoma in situ (n=78); and invasive breast cancer (n=22). Benign cases were excluded due to the absence of specific abnormalities. Three experienced breast pathologists conducted an independent review of the 180 digital whole slide images, established a reference consensus diagnosis and marked one or more diagnostic ROIs for each case. Forty-four participating pathologists independently diagnosed and marked ROIs on the images. Participant diagnoses and ROI were compared with consensus reference diagnoses and ROI. Regression models tested whether percent overlap between participant ROI and consensus reference ROI predicted diagnostic accuracy. Each of the 44 participants interpreted 39-50 cases for a total of 1972 individual diagnoses. Percent ROI overlap with the expert reference ROI was higher in pathologists who self-reported academic affiliation (69 vs 65%, P=0.002). Percent overlap between participants' ROI and consensus reference ROI was then classified into ordinal categories: 0, 1-33, 34-65, 66-99 and 100% overlap. For each incremental change in the ordinal percent ROI overlap, diagnostic agreement increased by 60% (OR 1.6, 95% CI (1.5-1.7), P<0.001) and the association remained significant even after adjustment for other covariates. The magnitude of the association between ROI overlap and diagnostic agreement increased with increasing diagnostic severity. The findings indicate that pathologists are more likely to converge with an expert reference diagnosis when they identify an overlapping diagnostic image region, suggesting that future computer-aided detection systems that highlight potential diagnostic regions could be a helpful tool to improve accuracy and education. PMID- 27198568 TI - Interobserver variability in intraductal papillary mucinous neoplasm subtypes and application of their mucin immunoprofiles. AB - Intraductal papillary mucinous neoplasm is considered a precursor lesion to pancreatic adenocarcinoma. These are further classified into four histologic subtypes: gastric, intestinal, pancreatobiliary, and oncocytic. The first aim of this study was to assess the interobserver variability among five gastrointestinal pathologists in diagnosing intraductal papillary mucinous neoplasm subtypes by morphology alone. The second aim of the study was to compare intraductal papillary mucinous neoplasm subtypes, which received consensus diagnoses (>=80% agreement) with their respective mucin immunoprofiles (MUC1, MUC2, MUC5AC, MUC6, and CDX2). A consensus histologic subtype was reached in 58% of cases (29/50) among the five gastrointestinal pathologists. Overall there was moderate agreement (kappa=0.41, P<0.01) in subtyping intraductal papillary mucinous neoplasms without the use of immunohistochemistry. The histologic subtype with the best interobserver agreement was intestinal type (kappa=0.56, P<0.01) followed by pancreatobiliary, gastric, mixed, and oncocytic types (kappa=0.43, P<0.01; kappa=0.38, P<0.01; kappa=0.17, P<0.01; kappa=0.08, P<0.04, respectively). Both kappa values for mixed and oncocytic subtypes were likely artificially low due to the underrepresentation of these subtypes in this study and not a true indication of poor interobserver agreement. Following an intradepartmental consensus meeting between two gastrointestinal pathologists, 68% of cases (34/50) received a consensus intraductal papillary mucinous neoplasm subtype. Sixty-nine percent of cases (11/16) that did not receive a consensus intraductal papillary mucinous neoplasm subtype could be classified based on their respective immunoprofiles. Standardizing the use of immunohistochemistry with a mucin immunopanel (MUC1, MUC2, MUC5AC, and MUC6) may improve the agreement of diagnosing intraductal papillary mucinous neoplasm histologic subtypes. PMID- 27198569 TI - PD-L1 expression in colorectal cancer is associated with microsatellite instability, BRAF mutation, medullary morphology and cytotoxic tumor-infiltrating lymphocytes. AB - Programmed cell death 1 (PD-1) and its ligand (PD-L1) are key suppressors of the cytotoxic immune response. PD-L1 expression on tumor cells may be induced by the immune microenvironment, resulting in immune escape (adaptive immune resistance), and an adverse prognosis in many malignancies. In colorectal carcinoma the response to PD-1/PD-L1 inhibition is correlated with microsatellite instability. However, little is known about the clinicopathologic, molecular, and prognostic characteristics of colorectal carcinoma with PD-L1 expression. We performed immunohistochemistry for PD-L1 on 181 cases of colorectal carcinoma with known microsatellite instability and mutational status, and correlated PD-L1 expression with clinicopathologic features including tumor-infiltrating lymphocyte burden/immunophenotype, tumor mutational profile, and disease-specific survival. PD-L1 was expressed in tumors from 16 patients (9%) who were more often older (P=0.006) and female (P=0.035), with tumors exhibiting a larger size (P=0.013), but lower stage (P<0.001). PD-L1 expression was associated with increased CD8 and TBET-positive tumor-infiltrating lymphocytes, medullary phenotype, poor differentiation, microsatellite instability, BRAF mutation (P<0.001 for each), and a lower frequency of KRAS mutation (P=0.012). On multivariate analysis, PD-L1 expression was associated with medullary morphology and frequent CD8-positive tumor-infiltrating lymphocytes, suggesting adaptive immune resistance. PD-L1 positivity was not predictive of survival in the entire cohort, but it was associated with a lower disease-specific survival within the microsatellite instability high cohort. PD-L1 expression in colorectal carcinoma is associated with clinicopathologic and molecular features of the serrated pathway of colorectal carcinogenesis, and is associated with a worse outcome within microsatellite-unstable tumors. These findings support the role of PD-L1 expression in providing normally immunogenic colorectal carcinoma a means of immune evasion and a more aggressive biology, provide a potential mechanistic explanation for the favorable response of microsatellite-unstable colorectal carcinoma to PD-1/PD-L1 pathway blockade, and suggest potential predictive and prognostic roles of PD-L1 immunohistochemistry in colorectal carcinoma. PMID- 27198572 TI - A Vitamin on the Mind: New Discoveries on Control of the Brain by Vitamin A. AB - Vitamin A is essential for many physiological processes and is particularly crucial during early life, when vitamin A deficiency increases mortality through elevated rates of infection. This deadly aspect of vitamin A deficiency masks other effects that, while not lethal, may nevertheless cause significant issues if vitamin A insufficiency reoccurs during later childhood or in the adult. One such effect is on the brain. Vitamin A is essential for several regions of the brain, and this chapter focuses on two regions: the hippocampus, needed for learning and memory, and the hypothalamus, necessary to maintain the body's internal physiological balance. Vitamin A, through its active metabolite retinoic acid, is required to support neuroplasticity in the hippocampus, and vitamin A deficiency has a dramatic effect on depressing learning and memory. The effects of vitamin A deficiency on the hypothalamus may lead to depression of appetite and growth. Much of this research has relied on animal studies, and it will be essential in the future to determine the full role of vitamin A in the human brain. PMID- 27198570 TI - Colorectal tumor molecular phenotype and miRNA: expression profiles and prognosis. AB - MiRNAs regulate gene expression by post-transcriptionally suppressing mRNA translation or by causing mRNA degradation. It has been proposed that unique miRNAs influence specific tumor molecular phenotype. In this paper, we test the hypotheses that miRNA expression differs by tumor molecular phenotype and that those differences may influence prognosis. Data come from population-based studies of colorectal cancer conducted in Utah and the Northern California Kaiser Permanente Medical Care Program. A total of 1893 carcinoma samples were run on the Agilent Human miRNA Microarray V19.0 containing 2006 miRNAs. We assessed differences in miRNA expression between TP53-mutated and non-mutated, KRAS mutated and non-mutated, BRAF-mutated and non-mutated, CpG island methylator phenotype (CIMP) high and CIMP low, and microsatellite instability (MSI) and microsatellite stable (MSS) colon and rectal tumors. Using a Cox proportional hazard model we evaluated if those miRNAs differentially expressed by tumor phenotype influenced survival after adjusting for age, sex, and AJCC stage. There were 22 differentially expressed miRNAs for TP53-mutated colon tumors and 5 for TP53-mutated rectal tumors with a fold change of >1.49 (or <0.67). Additionally, 13 miRNAS were differentially expressed for KRAS-mutated rectal tumors, 8 differentially expressed miRNAs for colon CIMP high tumors, and 2 differentially expressed miRNAs for BRAF-mutated colon tumors. The majority of differentially expressed miRNAS were observed between MSI and MSS tumors (94 differentially expressed miRNAs for colon; 41 differentially expressed miRNAs for rectal tumors). Of these miRNAs differentially expressed between MSI and MSS tumors, the majority were downregulated. Ten of the differentially expressed miRNAs were associated with survival; after adjustment for MSI status, five miRNAS, miR-196b 5p, miR-31-5p, miR-99b-5p, miR-636, and miR-192-3p, were significantly associated with survival. In summary, it appears that the majority of miRNAs that are differentially expressed by tumor molecular phenotype are MSI tumors. However, these miRNAs appear to have minimal effect on prognosis. PMID- 27198571 TI - Microsurgical removal of craniopharyngioma: endoscopic and transcranial techniques for complication avoidance. AB - Craniopharyngioma remains a challenging entity for neurosurgeons because of its midline, deep seated location and intimate relationship with critical neurovascular structures. Although gross total resection is ideal, the need to reduce surgical morbidity and preserve quality of life has led to a number of neurosurgical approaches which have attained this goal. Here we discuss the commonly used approaches for surgical resection and highlight technical considerations to reduce the potential of complications. We also discuss the mutually exclusive underlying genetic lesions in different histopathological subtypes that will likely lead to future treatment options for these tumors. PMID- 27198573 TI - Corrigendum: White-nose syndrome without borders: Pseudogymnoascus destructans infection tolerated in Europe and Palearctic Asia but not in North America. PMID- 27198574 TI - Nrf2/Keap1 system regulates vascular smooth muscle cell apoptosis for vascular homeostasis: role in neointimal formation after vascular injury. AB - Abnormal increases in vascular smooth muscle cells (VSMCs) in the intimal region after a vascular injury is a key event in developing neointimal hyperplasia. To maintain vascular function, proliferation and apoptosis of VSMCs is tightly controlled during vascular remodeling. NF-E2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1) system, a key component of the oxidative stress response that acts in maintaining homeostasis, plays an important role in neointimal hyperplasia after a vascular injury; however, the role of Nrf2/Keap1 in VSMC apoptosis has not been clarified. Here we report that 14 days after arterial injury in mice, TUNEL-positive VSMCs are detected in both the neointimal and medial layers. These layers contain cells expressing high levels of Nrf2 but low Keap1 expression. In VSMCs, Keap1 depletion induces features of apoptosis, such as positive TUNEL staining and annexin V binding. These changes are associated with an increased expression of nuclear Nrf2. Simultaneous Nrf2 depletion inhibits Keap1 depletion-induced apoptosis. At 14 days after the vascular injury, Nrf2-deficient mice demonstrated fewer TUNEL-positive cells and increased neointimal formation in the neointimal and medial areas. The results suggest that the Nrf2/Keap1 system regulates VSMC apoptosis during neointimal formation, thereby inhibiting neointimal hyperplasia after a vascular injury. PMID- 27198575 TI - Oncologist pays $300 000 to settle US claims of billing for fake cancer drug. PMID- 27198576 TI - Osteoblastic lesion screening with an advanced post-processing package enabling in-plane rib reading in CT-images. AB - BACKGROUND: To evaluate screening and diagnostic accuracy for the detection of osteoblastic rib lesions using an advanced post-processing package enabling in plane rib reading in CT-images. METHODS: We retrospectively assessed the CT-data of 60 consecutive prostate cancer patients by applying dedicated software enabling in-plane rib reading. Reading the conventional multiplanar reconstructions was considered to be the reference standard. To simulate clinical practice, the reader was given 10 s to screen for sclerotic rib lesions in each patient applying both approaches. Afterwards, every rib was evaluated individually with both approaches without a time limit. Sensitivities, specificities, positive/negative predictive values and the time needed for detection were calculated depending on the lesion's size (largest diameter < 5 mm, 5-10 mm, > 10 mm). RESULTS: In 53 of 60 patients, all ribs were properly displayed in plane, in five patients ribs were partially displayed correctly, and in two patients none of the ribs were displayed correctly. During the 10-s screening approach all patients with sclerotic rib lesions were correctly identified reading the in-plane images (including the patients without a correct rib segmentation), whereas 14 of 23 patients were correctly identified reading conventional multiplanar images. Overall screening sensitivity, specificity, and positive/negative predictive values were 100/27.0/46.0/100 %, respectively, for in-plane reading and 60.9/100/100/80.4 %, respectively, for multiplanar reading. Overall diagnostic (no time limit) sensitivity, specificity, and positive/negative predictive values of in-plane reading were 97.8/92.8/74.6/99.5 %, respectively. False positive results predominantly occurred for lesions <5 mm in size. CONCLUSIONS: In-plane reading of the ribs allows reliable detection of osteoblastic lesions for screening purposes. The limited specificity results from false positives predominantly occurring for small lesions. PMID- 27198577 TI - Effects of High-Definition and Conventional tDCS on Response Inhibition. AB - BACKGROUND: Response inhibition is a critical executive function, enabling the adaptive control of behavior in a changing environment. The inferior frontal cortex (IFC) is considered to be critical for response inhibition, leading researchers to develop transcranial direct current stimulation (tDCS) montages attempting to target the IFC and improve inhibitory performance. However, conventional tDCS montages produce diffuse current through the brain, making it difficult to establish causality between stimulation of any one given brain region and resulting behavioral changes. Recently, high-definition tDCS (HD-tDCS) methods have been developed to target brain regions with increased focality relative to conventional tDCS. OBJECTIVE: Remarkably few studies have utilized HD tDCS to improve cognitive task performance, however, and no study has directly compared the behavioral effects of HD-tDCS to conventional tDCS. METHODS: In the present study, participants received either HD-tDCS or conventional tDCS to the IFC during performance of a response inhibition task (stop-signal task, SST) or a control task (choice reaction time task, CRT). A third group of participants completed the same behavioral protocols, but received tDCS to a control site (mid occipital cortex). Post-stimulation improvement in SST performance was analyzed as a function of tDCS group and the task performed during stimulation using both conventional and Bayesian parameter estimation analyses. RESULTS: Bayesian estimation of the effects of HD- and conventional tDCS to IFC relative to control site stimulation demonstrated enhanced response inhibition for both conditions. No improvements were found after control task (CRT) training in any tDCS condition. CONCLUSION: Results support the use of both HD- and conventional tDCS to the IFC for improving response inhibition, providing empirical evidence that HD-tDCS can be used to facilitate performance on an executive function task. PMID- 27198578 TI - Low-frequency Subthalamic Stimulation in Parkinson's Disease: Long-term Outcome and Predictors. AB - BACKGROUND: Parkinson's disease patients undergoing subthalamic nucleus deep brain stimulation (STN DBS) at standard frequency (>100 Hz) often develop gait impairment, postural instability and speech difficulties. Low frequency stimulation (<100 Hz, LFS) can improve such axial symptoms, but there are concerns that improvement may be transient. OBJECTIVE: To identify long-term outcome and predictors of low-frequency subthalamic stimulation in Parkinson's disease. METHODS: Through a chart review we identified 85 out of 324 STN DBS patients who received a trial of LFS and describe their characteristics and outcome predictors. RESULTS: Patients were switched to LFS (<100 Hz) 3.8 +/- 3.3 years after surgery. Most patients (64%) attained a subjective improvement of gait, speech or balance for 2.0 +/- 1.9 years. Motor scores improved within the first year after the stimulation change and showed a slower progression over time when compared to patients switched back to high frequency stimulation. UPDRS III axial score on medication before surgery and the y-axis coordinate of the active contact were independent predictors of LFS retention. CONCLUSIONS: This report provides evidence that the use of LFS yields an enduring benefit in a considerable percentage of patients who develop axial motor symptoms during conventional stimulation. PMID- 27198579 TI - An adaptive association test for microbiome data. AB - There is increasing interest in investigating how the compositions of microbial communities are associated with human health and disease. Although existing methods have identified many associations, a proper choice of a phylogenetic distance is critical for the power of these methods. To assess an overall association between the composition of a microbial community and an outcome of interest, we present a novel multivariate testing method called aMiSPU, that is joint and highly adaptive over all observed taxa and thus high powered across various scenarios, alleviating the issue with the choice of a phylogenetic distance. Our simulations and real-data analyses demonstrated that the aMiSPU test was often more powerful than several competing methods while correctly controlling type I error rates. The R package MiSPU is available at https://github.com/ChongWu-Biostat/MiSPU and CRAN. PMID- 27198580 TI - Changes in Implantation Patterns and Therapy Rates of Implantable Cardioverter Defibrillators over Time in Ischemic and Dilated Cardiomyopathy Patients. AB - BACKGROUND: Clinical guidelines on implantable cardioverter defibrillator (ICD) therapy changed significantly in the last decades with potential inherent effects on therapy efficacy. We aimed to study therapy rates in time and the association between therapies and mortality. METHODS: All patients receiving an ICD, primary and secondary prevention, were included in a single-center retrospective registry. Information on first appropriate and inappropriate therapies was documented. Dates of implant were divided in P1: 1996-2001, P2: 2002-2008, and P3: 2009-2014. RESULTS: A total of 727 patients, 84.9% male-66.4% ischemic cardiomyopathy (ICM)-56% primary prevention-mean follow-up 5.2 +/- 4.1 years, were included. There was a shift from secondary to primary prevention indications, from ischemic to non-ICM, and from single chamber to cardiac resynchronization therapy defibrillator devices. The annual 1- and 3-year appropriate shock (AS) rate declined from 29.4% and 15.1% in P1, over 13.3% and 9.2% in P2 to 7.8% and 5.7% in P3 (log-rank P < 0.001), while inappropriate shock (IAS) rates remained unchanged (log-rank P = 0.635). After multivariate regression analysis a higher age at implant, lower left ventricular ejection fraction, history of stroke, diabetes mellitus, intake of loop diuretics or digitalis, higher creatinine, and longer QTc were independent predictors of mortality. CONCLUSION: These changes in clinical practice with a shift to primary prevention and rise in non-ICM implants caused a significant decrease in AS incidence, while IAS remained stable. Receiving AS or IAS was not an independent predictor of mortality in our real-life cohort. PMID- 27198581 TI - Combined MEG and pT-TMS study in Parkinson's disease. AB - Magnetoencephalographic (MEG) recordings of the brain in Parkinson's disease were obtained in order to look for possible effect of pico-Tesla transcranial magnetic stimulation (pT-TMS). We found a significant effect of an increase of frequencies in the range of 2-7 Hz across subjects. In addition, we observed the mean peak frequency difference within the 2-7 Hz band towards frequencies of less or equal to those frequencies of the alpha frequency range (8-13 Hz). PMID- 27198582 TI - Human Urine-Fueled Light-Driven NADH Regeneration for Redox Biocatalysis. AB - Human urine is considered as an alternative source of hydrogen and electricity owing to its abundance and high energy density. Here we show the utility of human urine as a chemical fuel for driving redox biocatalysis in a photoelectrochemical cell. Ni(OH)2 -modified alpha-Fe2 O3 is selected as a photoanode for the oxidation of urea in human urine and black silicon (bSi) is used as a photocathode material for nicotinamide cofactor (NADH: hydrogenated nicotinamide adenine dinucleotide) regeneration. The electrons extracted from human urine are used for the regeneration of NADH, an essential hydride mediator that is required for numerous redox biocatalytic reactions. The catalytic reactions at both the photoanode and the photocathode were significantly enhanced by light energy that lowered the overpotential and generated high currents in the full cell system. PMID- 27198583 TI - Adverse Drug Reactions in Patients Receiving Systemic Antifungal Therapy at a High-Complexity Hospital. AB - The aim of the present study was to determine the frequency of adverse drug reactions (ADRs) associated with the use of systemic antifungal drugs in patients hospitalized at a high-complexity hospital. In addition, factors associated with ADRs were investigated. This cross-sectional retrospective study involved the investigation of 183 medical records of patients receiving systemic antifungal therapy. Antifungal drugs were classified using the fourth level of the Anatomical Therapeutic Chemical System. ADR causality was classified using the Naranjo algorithm. Drug interactions were assessed using DRUG-REAX software. Data were analyzed with descriptive statistics and univariate and multivariate logistic regression. A total of 53 patients (29.0%) had at least 1 ADR involving antifungals. Ninety-six ADRs were detected. The main ADRs observed were an infusion reaction in 24 patients (25.0%), hypokalemia in 22 (22.9%), nephrotoxicity in 18 (18.7%), and hepatotoxicity in 15 (15.6%). Amphotericin B and voriconazole were associated with ADRs of major clinical impact. Eleven of the ADRs (11.4%) were related to drug interactions. The following 3 factors were contributors to the multivariate model for the occurrence of ADRs caused by antifungal drug use: neoplasm diagnosis (odds ratio [OR], 3.9; 1.9-7.9), length of hospital stay (OR, 2.2; 1.1-4.5), and the use of >=13 drugs (OR, 3.4; 1.6 7.2). Our study revealed positive associations between the occurrence of ADRs and diagnosis of a neoplasm, the length of stay, and the use of multiple drugs concomitant with antifungals. These risk factors should be considered in antifungal stewardship, among other actions, to promote the rational use of antifungal agents. PMID- 27198585 TI - Approaches to promoting the appropriate use of antibiotics through hospital electronic prescribing systems: a scoping review. AB - OBJECTIVE: To identify approaches of using stand-alone and more integrated hospital ePrescribing systems to promote and support the appropriate use of antibiotics, and identify gaps in order to inform future efforts in this area. METHODS: A systematic scoping review of the empirical literature from 1997 until 2015, searching the following databases: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Google Scholar, Clinical Trials, International Standard Randomised Controlled Trial Number Registry, Economic Evaluation database and International Prospective Register of Systematic Reviews. Search terms related to different components of systems, hospital settings and antimicrobial stewardship. Two reviewers independently screened papers and mutually agreed papers for inclusion. We undertook an interpretive synthesis. KEY FINDINGS: We identified 143 papers. The majority of these were single-centre observational studies from North American settings with a wide range of system functionalities. Most evidence related to computerised decision support (CDS) and computerised physician order entry (CPOE) functionalities, of which many were extensively customised. We also found some limited work surrounding integration with laboratory results, pharmacy systems and organisational surveillance. Outcomes examined included healthcare professional performance, patient outcomes and health economic evaluations. We found at times conflicting conclusions surrounding effectiveness, which may be due to heterogeneity of populations, technologies and outcomes studied. Reports of unintended consequences were limited. CONCLUSIONS: Interventions are centred on CPOE and CDS, but also include additional functionality aiming to support various facets of the medicines management process. Wider organisational dimensions appear important to supporting adoption. Evaluations should consider processes, clinical, economic and safety outcomes in order to generate generalisable insights into safety, effectiveness and cost-effectiveness. PMID- 27198584 TI - Inhibiting Hexamer Disassembly of Human UDP-Glucose Dehydrogenase by Photoactivated Amino Acid Cross-Linking. AB - The enzyme UDP-glucose dehydrogenase (UGDH) catalyzes the reaction of UDP-glucose to UDP-glucuronate through two successive NAD(+)-dependent oxidation steps. Human UGDH apoprotein is purified as a mixture of dimeric and hexameric species. Addition of substrate and cofactor stabilizes the oligomeric state to primarily the hexameric form. To determine if the dynamic conformations of hUGDH are required for catalytic activity, we used site-specific unnatural amino acid incorporation to facilitate cross-linking of monomeric subunits into predominantly obligate oligomeric species. Optimal cross-linking was achieved by encoding p-benzoyl-l-phenylalanine at position 458, normally a glutamine located within the dimer-dimer interface, and exposing the enzyme to long wavelength ultraviolet (UV) radiation in the presence of substrate and cofactor. Hexameric complexes were purified by gel filtration chromatography and found to contain significant fractions of dimer and trimer (approximately 50%) along with another 10% higher-molecular mass species. The activity of the cross-linked enzyme was reduced by almost 60% relative to that of the un-cross-linked UGDH mutant, and UV exposure had no effect on the activity of the wild-type enzyme. These results support a model for catalysis in which the ability to dissociate the dimer-dimer interface is as important for maximal enzyme function as has been previously shown for the formation of the hexamer. PMID- 27198586 TI - Effect of expiratory muscle strength training on swallowing-related muscle strength in community-dwelling elderly individuals: a randomized controlled trial. AB - OBJECTIVE: This study aimed to investigate the effect of expiratory muscle strength training (EMST) on swallowing-related muscle strength in community dwelling elderly individuals. BACKGROUND: Expiratory muscle strength training is an intervention for patients with oropharyngeal dysphagia. This training is associated with respiration, coughing, speech and swallowing, and its effectiveness has been proven in previous studies. However, the effects of EMST on elderly individuals and evidence are still lacking. MATERIALS AND METHODS: This study included 24 community-dwelling senior citizens aged >=65 years (12 men and 12 women). The experimental group trained at the 70% threshold value of the maximum expiratory pressure using an EMST device 5 days per week for 4 weeks and comprised five sets of five breaths through the device for 25 breaths per day. The placebo group trained with a resistance-free sham device. Post-intervention, muscle strength of the bilateral buccinator and the orbicularis oris muscles (OOM) was measured using the Iowa Oral Performance Instrument. Surface electromyography was used to measure activation of the suprahyoid muscles (SM). RESULTS: After intervention, the strength of the buccinator and the OOM in the experimental group showed statistically significant improvement. There was also statistically significant activation of the SM. In the placebo group, the strength of the orbicularis oris muscle alone improved. No statistically significant differences between groups were found for the strength of the buccinator and the OOM and the activation of the SM. CONCLUSION: EMST had a positive effect on swallowing-related muscle strength in elderly participants. PMID- 27198587 TI - Nanoparticle-Enabled Selective Destruction of Prostate Tumor Using MRI-Guided Focal Photothermal Therapy. AB - BACKGROUND: The Magnetic Resonance Imaging (MRI)-guided focal laser therapy has shown early promise in Phase 1 trial treating low/intermediate-risk localized prostate cancer (PCa), but the lack of tumor selectivity and low efficiency of heat generation remain as drawbacks of agent-free laser therapy. Intrinsic multifunctional porphyrin-nanoparticles (porphysomes) have been exploited to treat localized PCa by MRI-guided focal photothermal therapy (PTT) with significantly improved efficiency and tumor selectivity over prior methods of PTT, providing an effective and safe alternative to active surveillance or radical therapy. METHODS: The tumor accumulation of porphysomes chelated with copper-64 was determined and compared with the clinic standard (18) F-FDG in an orthotropic PCa mouse model by positron emission tomography (PET) imaging, providing quantitative assessment for PTT dosimetry. The PTT was conducted with MRI-guided light delivery and monitored by MR thermometry, mimicking the clinical protocol. The efficacy of treatment and adverse effects to surround tissues were evaluated by histology analysis and tumor growth in survival study via MRI. RESULTS: Porphysomes showed superior tumor-to-prostate selectivity over (18) F FDG (6:1 vs. 0.36:1). MR thermometry detected tumor temperature increased to >=55 degrees C within 2 min (671 nm at 500 mW), but minimal increase in surrounding tissues. Porphysome enabled effective PTT eradication of tumor without damaging adjacent organs in orthotropic PCa mouse model. CONCLUSIONS: Porphysome-enabled MRI-guided focal PTT could be an effective and safe approach to treat PCa at low risk of progression, thus addressing the significant unmet clinical needs and benefiting an ever-growing number of patients who may be over-treated and risk unnecessary side effects from radical therapies. Prostate 76:1169-1181, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27198588 TI - Minimally invasive flapless vs. flapped approach for single implant placement: a 2-year randomized controlled clinical trial. AB - PURPOSE: The purpose of this 2-year randomized controlled clinical trial was to assess the differences in implant survival rates, soft tissue preservation, patient centered outcome and crestal bone changes applying the minimally invasive (MI) flapless approach for single implant placement compared to flapped implant surgery (FS). MATERIALS AND METHODS: Subjects eligible for this study were randomly assigned into two groups: MI or FS. Items of evaluation were the following: implant installation position, soft tissue healing, post-surgical pain, soft tissue outcome, marginal bone loss (MBL), and implant survival rate. RESULTS: Forty subjects (14 women and 26 men, 20 in MI group and 20 in FS group with a mean of 39 +/- 13.2 years old) were included in the study. None of the implants demonstrated dehiscence or loss during the follow-up. Subjects in MI group showed significantly lower post-surgical pain and significantly less wound healing index scores at 1-week follow-up. The width of keratinized mucosa decreased from a mean of 4.2 +/- 1.6 mm pre-surgically to 3.7 +/- 1.1 mm at crown delivery but remained stable at 2-year follow-up in MI group. At every appointment in the study, no statistical significant difference of PD and MBL was found between the two groups. CONCLUSION: Compared with FS, single implants placed applying the MI technique in selected subjects showed advantages in improving patient comfort and decreasing post-implant placement soft tissue reaction. Meanwhile, implants with MI approach have the same level of MBL and high success rates as FS procedure at 2-year follow-up. The deduction of keratinized mucosa is very limited and the width of KM remained stable with MI approach at 2-year follow-up. PMID- 27198589 TI - Dietary patterns and benign breast diseases: a case-control study. AB - Several studies have investigated the relation between benign breast diseases (BBD) and food intake. However, dietary patterns of these patients have not been taken into consideration up to now. The aim of this study is to determine the association between dietary patterns and BBD. In this case-control study, ninety six patients with BBD and seventy controls were selected from women attending the Iranian Center for Breast Cancer affiliated with Academic Center for Education, Culture and Research. Demographic, physical activity and semi-quantitative FFQ were completed. The main dietary patterns were extracted by factor analysis. Two major dietary patterns emerged: Healthy dietary pattern including fish, poultry, eggs, low-fat dairy products, vegetables, legumes, nuts and seeds, whole grains, oil and mayonnaise, olives, fruits; and Unhealthy dietary pattern including red meats, organ and processed meats, high-fat dairy products, refined grains, sweets and desserts, animal and solid fats. After adjustment for age, BMI and energy intake, the participants in the highest tertile of Healthy dietary pattern (OR 0.44; 95 % CI 0.20, 0.99) were less likely to have BBD compared with those in the first tertile. After adjustment for other confounding variables, this relationship still remained close to significant level. However, higher consumption of Unhealthy dietary pattern was not associated with the risk of BBD. In conclusion, Healthy dietary pattern might be inversely associated with the risk of BBD; however, this result should be interpreted with caution. Future studies are needed to confirm our findings. PMID- 27198592 TI - Welcome Message. PMID- 27198590 TI - Ranges of motion after reverse shoulder arthroplasty improve significantly the first year after surgery in patients with rheumatoid arthritis. AB - OBJECTIVES: To evaluate the trajectory of the change in range of motion after reverse shoulder joint replacement during 3-year follow-up among patients with rheumatoid arthritis. METHODS: Retrospective cohort longitudinal study of 76 shoulder replacements performed in a university clinic. The range of shoulder motion was assessed by a physiotherapist using a manual goniometer with 5-degree precision before the surgery and 1, 3, 6, 12, and 36 months postoperatively. RESULTS: The shapes of the regression curves suggest that the improvement or decline observed in joint motion was happening mostly during the first year after surgery. After 1 year, the trajectories become flat and they remained unchanged until the end of follow-up. CONCLUSIONS: After shoulder joint replacement, the range of shoulder motion showed substantial changes during the first year only. This should be taken into account when scheduling control visits, planning rehabilitation, and predicting the use of community services after the surgery. PMID- 27198598 TI - Poster Presentations. PMID- 27198591 TI - A new framing approach in guideline development to manage different sources of knowledge. AB - RATIONALE: Contemporary guideline methodology struggles to consider context and information from different sources of knowledge besides quantitative research. Return to work programmes involve multiple components and stakeholders. If the guideline is to be relevant and practical for a complex intervention such as return to work, it is essential to use broad sources of knowledge. AIMS AND OBJECTIVE: This paper reports on a new method in guideline development to manage different sources of knowledge. METHODS: The method used framing for the return to-work guidance within the Clinical Practice Guidelines for the Management of Rotator Cuff Syndrome in the Workplace. The development involved was a multi disciplinary working party of experts including consumers. The researchers considered a broad range of research, expert (practice and experience) knowledge, the individual's and workplace contexts, and used framing with the International Classification of Functioning, Disability and Health. Following a systematic database search on four clinical questions, there were seven stages of knowledge management to extract, unpack, map and pack information to the ICF domains framework. Companion graded recommendations were developed. RESULTS: The results include practical examples, user and consumer guides, flow charts and six graded or consensus recommendations on best practice for return to work intervention. CONCLUSIONS: Our findings suggest using framing in guideline methodology with internationally accepted frames such as the ICF is a reliable and transparent framework to manage different sources of knowledge. Future research might examine other examples and methods for managing complexity and using different sources of knowledge in guideline development. PMID- 27198596 TI - Symposiums. PMID- 27198599 TI - Satellite Symposiums. PMID- 27198601 TI - Clogging-free microfluidics for continuous size-based separation of microparticles. AB - In microfluidic filtration systems, one of the leading obstacles to efficient, continuous operation is clogging of the filters. Here, we introduce a lateral flow microfluidic sieving (MU-sieving) technique to overcome clogging and to allow continuous operation of filter based microfluidic separation. A low frequency mechanical oscillation was added to the fluid flow, which made possible the release of aggregated unwanted polystyrene (PS) particles trapped between the larger target PS particles in the filter demonstrating continuous MU-sieving operation. We achieved collection of the target PS particles with 100% separation efficiency. Also, on average, more than 98% of the filtered target particles were retrieved after the filtration showing high retrieval rates. Since the oscillation was applied to the fluid but not to the microfluidic filter system, mechanical stresses to the system was minimized and no additional fabrication procedures were necessary. We also applied the MU-sieving technique to the separation of cancer cells (MDA-MB-231) from whole blood and showed that the fluidic oscillations prevented the filters from being blocked by the filtered cancer cells allowing continuous microfluidic separation with high efficiency. PMID- 27198602 TI - Splicing factors control C. elegans behavioural learning in a single neuron by producing DAF-2c receptor. AB - Alternative splicing generates protein diversity essential for neuronal properties. However, the precise mechanisms underlying this process and its relevance to physiological and behavioural functions are poorly understood. To address these issues, we focused on a cassette exon of the Caenorhabditis elegans insulin receptor gene daf-2, whose proper variant expression in the taste receptor neuron ASER is critical for taste-avoidance learning. We show that inclusion of daf-2 exon 11.5 is restricted to specific neuron types, including ASER, and is controlled by a combinatorial action of evolutionarily conserved alternative splicing factors, RBFOX, CELF and PTB families of proteins. Mutations of these factors cause a learning defect, and this defect is relieved by DAF-2c (exon 11.5+) isoform expression only in a single neuron ASER. Our results provide evidence that alternative splicing regulation of a single critical gene in a single critical neuron is essential for learning ability in an organism. PMID- 27198603 TI - Fluctuation of Viremia in Hepatitis B Virus-Infected Healthcare Workers Performing Exposure-Prone Procedures in the Netherlands. AB - OBJECTIVE: To determine the longitudinal changes in viral load of hepatitis B virus (HBV)-infected healthcare workers (HCWs) and its consequences for exclusion of infected HCWs performing exposure-prone procedures, various HBV DNA safety thresholds, and the frequency of monitoring. DESIGN: Retrospective cohort study June 1, 1996-January 31, 2013. Participants In the Netherlands, chronically HBV infected HCWs performing exposure-prone procedures are notified to the Committee for Prevention of Iatrogenic Hepatitis B. Of the 126 notified HCWs, 45 had 2 or more HBV DNA levels determined without antiviral therapy. METHODS: A time-to event analysis for HBV-infected HCWs categorized in various viremia levels surpassing a HBV DNA threshold level of 1*105 copies/mL, above which exposure prone procedures are not allowed in the Netherlands. RESULTS: Fluctuations of HBV DNA in follow-up samples ranged from -5.4 to +2.2 log10 copies/mL. A high correlation was seen for each HBV DNA level with the 3 previous levels. In a time to-event analysis, after 6 months 7.2%, 6.5%, and 14.3% of individuals had surpassed the threshold of 1*105 copies/mL for viral load categories 4.8*103 to 1.5*104; 1.5*104 to 4.0*104; and 4.0*104 to 1.0*105, respectively. CONCLUSIONS: We propose standard retesting every 6 months, with more frequent retesting just below the high threshold value (1*105 copies/mL), and prolonging this standard interval to 1 year after 3 consecutive levels below the threshold in policies with lower safety thresholds (1*103 or 1*104 copies/mL). Infect Control Hosp Epidemiol 2016;37:655-660. PMID- 27198604 TI - Predictors of Heavy Stethoscope Contamination Following a Physical Examination. AB - BACKGROUND The degree of bacterial contamination of stethoscopes can vary significantly following a physical examination. OBJECTIVE To conduct a prospective study to investigate the impact of various environmental and patient characteristics on stethoscope contamination. METHODS Following a standardized examination, the levels of bacterial contamination of 4 regions of the physicians' hands and 2 sections of the stethoscopes, and the presence of different pathogenic bacteria, were assessed. Predictors of heavy stethoscope contamination were identified through multivariate logistic regression. RESULTS In total, 392 surfaces were sampled following examination of 56 patients. The microorganisms most frequently recovered from hands and stethoscopes were Enterococcus spp. (29% and 20%, respectively) and Enterobacteriaceae (16% and 7%, respectively). Staphylococcus aureus (either methicillin susceptible or resistant), extended-spectrum beta-lactamase-producing Enterobacteriaceae, and Acinetobacter baumannii were recovered from 4%-9% of the samples from either hands or stethoscopes. There was a correlation between the likelihood of recovering these pathogens from the stethoscopes vs from the physicians' hands (rho=0.79; P=.04). The level of patient's skin contamination was an independent predictor of contamination of the stethoscope diaphragm (adjusted odds ratio [aOR], 1.001; P=.007) and tube (aOR, 1.001; P=.003). Male sex (aOR, 28.24; P=.01) and reception of a bed bath (aOR, 7.52; P=.048) were also independently associated with heavy tube contamination. CONCLUSIONS Stethoscope contamination following a single physical examination is not negligible and is associated with the level of contamination of the patient's skin. Prevention of pathogen dissemination is needed. Infect Control Hosp Epidemiol 2016;37:673-679. PMID- 27198606 TI - Colonization With Vancomycin-Resistant Enterococci After Discharge From an Epidemic Ward: Results of Outpatient Contact Screening by Visiting Nurses. PMID- 27198605 TI - Sampling Surfaces for Ebola Virus Persistence After Cleaning Procedures in High Level Isolation Settings: The Experience With 2 Patients at the Lazzaro Spallanzani National Institute for Infectious Diseases. PMID- 27198608 TI - Verbal Communication With Providers Improves Acceptance of Antimicrobial Stewardship Interventions. PMID- 27198607 TI - Antimicrobial Stewardship Programs: Engaging Project Managers to Increase Productivity. PMID- 27198610 TI - alpha-Galactosylceramide-activated murine NK1.1(+) invariant-NKT cells in the myometrium induce miscarriages in mice. AB - Innate immunity, which is unable to discriminate self from allo-antigens, is thought to be important players in the induction of miscarriages. Here, we show that the administration of IL-12 to syngeneic-mated C57BL/6 mice on gestation day 7.5 (Gd 7.5), drives significant miscarriages in pregnant females. Furthermore, the administration on Gd 7.5 of alpha-galactosylceramide (alpha-GalCer), which is known to activate invariant natural killer T (iNKT) cells, induced miscarriages in both syngeneic-mated C57BL/6 mice and allogeneic-mated mice (C57BL/6 (?) * BALB/c (?)). Surprisingly, the percentages of both DEC-205(+) DCs and CD1d restricted NK1.1(+) iNKT cells were higher in the myometrium of pregnant mice treated i.p. with alpha-GalCer than in the decidua. IL-12 secreted from alpha GalCer-activated DEC-205(+) DCs stimulated the secretion of cytokines, including IL-2, IL-4, IFN-gamma, TNF-alpha, perforin, and granzyme B, from the NK1.1(+) iNKT cells in the myometrium, leading to fetal loss in pregnant mice. Finally, the i.p. administration of IL-12 and/or alpha-GalCer in iNKT-deficient Jalpha18( /-) (Jalpha18 KO) mice did not induce miscarriages. This study provides a new perspective on the importance of the myometrium, rather than the decidua, in regulating pregnancy and a mechanism of miscarriage mediated by activated DEC 205(+) DCs and NK1.1(+) iNKT cells in the myometrium of pregnant mice. PMID- 27198612 TI - Using Brownian motion to measure shape asymmetry in mesoscopic matter using optical tweezers. AB - We propose a new method for quantifying shape asymmetry on the mesoscopic scale. The method takes advantage of the intrinsic coupling between rotational and translational Brownian motion (RBM and TBM, respectively) which happens in the case of asymmetric particles. We determine the coupling by measuring different correlation functions of the RBM and TBM for single, morphologically different, weakly trapped red blood cells in optical tweezers. The cells have different degrees of asymmetry that are controllably produced by varying the hypertonicity of their aqueous environment. We demonstrate a clear difference in the nature of the correlation functions both qualitatively and quantitatively for three types of cells having a varying degree of asymmetry. This method can have a variety of applications ranging from early stage disease diagnosis to quality control in microfabrication. PMID- 27198611 TI - MAGNETIC RESONANCE IMAGING SCORING OF AN EXPERIMENTAL MODEL OF POST-TRAUMATIC OSTEOARTHRITIS IN THE EQUINE CARPUS. AB - Magnetic resonance imaging (MRI) is the most sensitive imaging modality to detect the early changes of osteoarthritis. Currently, there is no quantifiable method to tract these pathological changes over time in the horse. The objective of this experimental study was to characterize the progression of MRI changes in an equine model of post-traumatic osteoarthritis using a semiquantitative scoring system for whole-organ evaluation of the middle carpal joint. On day 0, an osteochondral fragment was created in one middle carpal joint (OCI) and the contralateral joint (CON) was sham-operated in 10 horses. On day 14, study horses resumed exercise on a high-speed treadmill until the completion of the study (day 98). High-field MRI examinations were performed on days 0 (preosteochondral fragmentation), 14, and 98 and scored by three blinded observers using consensus agreement. Images were scored based on 15 independent articular features, and scores were compared between and within-groups. On days 14 and 98, OCI joints had significantly (P <= 0.05) higher whole-organ median scores (29.0 and 31.5, respectively), compared to CON joints (21.5 and 20.0, respectively). On day 14, OCI joints showed significant increases in high-signal bone lesion scores, and osteochondral fragment number and size. On day 98, high-signal bone lesion, low signal bone lesion, osteophyte formation, cartilage signal abnormality, subchondral bone irregularity, joint effusion, and synovial thickening scores were significantly increased in OCI joints. Study results suggest that the MRI whole-organ scoring system reported here may be used to identify onset and progression of pathological changes following osteochondral injury. PMID- 27198615 TI - Asymmetric Michael Addition of Aldimino Esters with Chalcones Catalyzed by Silver/Xing-Phos: Mechanism-Oriented Divergent Synthesis of Chiral Pyrrolines. AB - The mechanism-oriented reaction design for the divergent synthesis of chiral molecules from simple starting materials is highly desirable. In this work, aromatic amide-derived nonbiarylatropisomer/silver (silver/Xing-Phos) complex was used to catalyze the Michael addition of glycine aldimino esters to chalcones and successfully applied to the subsequent cyclocondensation to afford substituted cis-Delta(1)-pyrroline derivatives with up to 98 % ee. Besides the inherent performance of the chiral Ag/Xing-Phos catalyst system, it was found that the workup of such reactions played an important role for the stereoselective construction of stereodivergent Delta(1)-pyrrolines, in which an epimerization of the cis-Delta(1)-pyrrolines to the trans-isomers during was revealed. PMID- 27198614 TI - Anti-C1q autoantibodies are linked to autoimmune thyroid disorders in pregnant women. AB - Anti-C1q antibodies (anti-C1q) have been implicated in the pathogenesis of autoimmune diseases, including autoimmune thyroid disorders (AITD). The aim of this study was to evaluate the association between anti-C1q and thyroid function in pregnancy-associated AITD. In 96 pregnant women screened positive for AITD (thyroid dysfunction and/or antibodies against thyroperoxidase - TPOAb), anti-C1q were measured during the 9-11th gestational week and after delivery (median 16 months after delivery), and compared to the corresponding serum levels of thyroid hormones. As controls, 80 healthy pregnant women, 72 non-pregnant AITD patients and 72 blood donors were included. In the non-pregnant AITD group, two serum samples >= 6 months apart were analysed. Compared to blood donors, anti-C1q levels were substantially higher in all pregnant women analysed. In pregnancy, anti-C1q levels were higher in the TPOAb-positive women than in controls (37 versus 17.5%, P < 0.0001). Anti-C1q-positive pregnant women screened positive for AITD had higher thyroid-stimulating hormone (TSH) levels than anti-C1q-negative women (2.41 versus 1.94 mU/l, P = 0.01), and TSH correlated positively with anti C1q (r = 0.226, P = 0.045) in the TPOAb-positive women. After delivery, serum levels of anti-C1q decreased in the positively screened TPOAb-negative women (8.8 versus 5.9 U/l, P = 0.002), but not in the TPOAb-positive ones, and they no longer correlated with TSH. Anti-C1q antibody levels increase during pregnancy in general and even more in the context of AITD, where they correlate with thyroid stimulating hormone levels. PMID- 27198616 TI - Homocysteine pre-treatment increases redox capacity in both endothelial and tumor cells. AB - OBJECTIVE: We studied the modulatory effects of homocysteine pre-treatment on the disulfide reduction capacity of tumor and endothelial cells. METHODS: Human MDA MB-231 breast carcinoma and bovine aorta endothelial cells were pre-treated for 1 24 hours with 0.5-5 mM homocysteine or homocysteine thiolactone. After washing to eliminate any rest of homocysteine or homocysteine thiolactone, cell redox capacity was determined by using a method for measuring disulfide reduction. RESULTS: Homocysteine pre-treatments for 1-4 hours at a concentration of 0.5-5 mM increase the disulfide reduction capacity of both tumor and endothelial cells. This effect cannot be fully mimicked by either cysteine or homocysteine thiolactone pre-treatments of tumor cells. DISCUSSION: Taken together, our data suggest that homocysteine can behave as an anti-oxidant agent by increasing the anti-oxidant capacity of tumor and endothelial cells. PMID- 27198617 TI - Screening of a virtual mirror-image library of natural products. AB - We established a facile access to an unexplored mirror-image library of chiral natural product derivatives using d-protein technology. In this process, two chemical syntheses of mirror-image substances including a target protein and hit compound(s) allow the lead discovery from a virtual mirror-image library without the synthesis of numerous mirror-image compounds. PMID- 27198613 TI - Lights, camera, action! Capturing the spliceosome and pre-mRNA splicing with single-molecule fluorescence microscopy. AB - The process of removing intronic sequences from a precursor to messenger RNA (pre mRNA) to yield a mature mRNA transcript via splicing is an integral step in eukaryotic gene expression. Splicing is carried out by a cellular nanomachine called the spliceosome that is composed of RNA components and dozens of proteins. Despite decades of study, many fundamentals of spliceosome function have remained elusive. Recent developments in single-molecule fluorescence microscopy have afforded new tools to better probe the spliceosome and the complex, dynamic process of splicing by direct observation of single molecules. These cutting-edge technologies enable investigators to monitor the dynamics of specific splicing components, whole spliceosomes, and even cotranscriptional splicing within living cells. WIREs RNA 2016, 7:683-701. doi: 10.1002/wrna.1358 For further resources related to this article, please visit the WIREs website. PMID- 27198618 TI - Healthcare costs and productivity costs of hand and wrist injuries by external cause: A population-based study in working-age adults in the period 2008-2012. AB - BACKGROUND: Hand and wrist injuries are very common at the Emergency Departments (ED), and among the most costly injury types in the working population. The purpose of this study was to explore the causes of non-trivial hand and wrist injuries (i.e., hand fractures, wrist fractures and complex soft-tissue injuries) in working-age adults in order to identify target areas for prevention. METHODS: Data were extracted from the Dutch Injury Surveillance System, from the National Hospital Discharge Registry and from a patient follow-up survey in working-age adults (aged 20-64 years) in the period 2008-2012. An incidence-based cost model was used to estimate healthcare costs, and an absenteeism model for estimating the productivity costs. Total costs were calculated by external cause, subdivided in their main categories (home, sports, work, traffic and violence) and their most important subclasses. RESULTS: Total costs of these injuries in The Netherlands were US $410 million per year, of which 75% (US $307 million) productivity costs. Males represented 66% (US $271 million) of the total costs. Within the male group, the group 35-49 years had the highest contribution to total costs (US $112 million), as well as the highest costs per case (US $10,675). Work-related injuries showed the highest costs per case (US $11,797), however, only 25% of the total costs were work-related. The top five causes in terms of total costs were: accidents at home (falls 23%, contact with an object 17%), traffic (cycling 9%) and work (industrial work 4%, and construction work 4%). CONCLUSION: Hand and wrist injuries are a major cause of healthcare and productivity costs in working-age adults. To reduce the costs to society, prevention initiatives should be targeted at major contributing causes, that are mainly related to activities at home (falls, contact with an object) and accidents at the road (cycling). PMID- 27198621 TI - The niobium oxoazides [NbO(N3)3], [NbO(N3)3.2CH3CN], [(bipy)NbO(N3)3], Cs2[NbO(N3)5] and [PPh4]2[NbO(N3)5]. AB - Niobium oxotriazide, [NbO(N3)3], was prepared in a fluoride-azide exchange reaction between [NbOF3] and an excess of Me3SiN3 in SO2 solution. In acetonitrile solution, the fluoride-azide exchange resulted in the isolation of the adduct [NbO(N3)3.2CH3CN]. The subsequent reaction of [NbO(N3)3] with 2,2' bipyridine (bipy) resulted in the isolation of the bipyridine adduct [(bipy)NbO(N3)3]. The pentaazido anion [NbO(N3)5](2-) was obtained by the reaction of [NbO(N3)3] with two equivalents of ionic azide. The novel niobium oxoazides were fully characterized by their vibrational spectra, impact, friction and thermal sensitivity data and, in the case of [(bipy)NbO(N3)3], Cs2[NbO(N3)5], and [PPh4]2[NbO2(N3)5] by their X-ray crystal structures. PMID- 27198620 TI - Dentist shortage: an analysis of dentists, practices, and populations in the underserved areas. AB - OBJECTIVES: The objectives of this study are to identify and describe the characteristics of dental underserved geographic areas. Understanding these characteristics is an important step in addressing access to dental care barriers. METHODS: Dental underserved areas were identified from the Health Resources and Services Administration (HRSA) database and converted to census tracts for analysis. Characteristics of dental underserved geographic areas were compared with areas not designated as underserved. Dental practices included in the Dun & Bradstreet Business information database were geocoded and analyzed according to the underserved designation of their location and census demographic data. Thus, the relationships between dental underserved status, practice, and population characteristics were evaluated. RESULTS: Dental underserved areas are more likely to comprise individuals with lower socio-economic status (income and education levels), higher levels of underrepresented population groups, and have lower population densities than non-underserved areas. The populations living in dental underserved areas are more likely to experience geographic, financial, and educational barriers to dental care. CONCLUSIONS: The study identifies the geographic and financial barriers to dental care access. These findings suggest that the likelihood of a market-driven solution to dental underserved geographic areas is low and support public sector interventions to improve the status quo. PMID- 27198623 TI - Pigment variations in Emiliania huxleyi (CCMP370) as a response to changes in light intensity or quality. AB - Many studies on photoacclimation examine the pigment responses to changes in light intensity, but variations in light climate in the aquatic environment are also related to changes in spectral composition. We have employed a high performance liquid chromatography method with improved resolution towards chlorophyll c and fucoxanthin-related xanthophylls to examine the pigment composition of Emiliania huxleyi CCMP 370 under different light intensities and spectral qualities. To maintain its photosynthetic performance, E. huxleyi CCMP370 promotes drastic pigment changes that can be either the interconversion of pigments in pools with the same basic chromophoric structure (Fucoxanthin type or chlorophyll c type), or the ex novo synthesis (Diatoxanthin). These changes are linked either to variations in light quality (Fucoxanthin related xanthophylls) or in light intensity (chlorophyll c3 /Monovinyl chlorophyll c3 , Diadinoxanthin/Diatoxanthin, beta,E-carotene/ beta,beta-carotene). Fucoxanthin and 19'-hexanoyloxyfucoxanthin proportions were highly dependent on spectral conditions. Whereas Fucoxanthin dominated in green and red light, 19' hexanoyloxyfucoxanthin prevailed under blue spectral conditions. Our results suggest that the huge pigment diversity enhanced the photoacclimative capacities of E. huxleyi to efficiently perform under changing light environments. The ubiquity and success in the global ocean as well as the capacity of E. huxleyi to form large surface blooms might be associated to the plasticity described here. PMID- 27198619 TI - Coevolution analysis of Hepatitis C virus genome to identify the structural and functional dependency network of viral proteins. AB - A novel computational approach of coevolution analysis allowed us to reconstruct the protein-protein interaction network of the Hepatitis C Virus (HCV) at the residue resolution. For the first time, coevolution analysis of an entire viral genome was realized, based on a limited set of protein sequences with high sequence identity within genotypes. The identified coevolving residues constitute highly relevant predictions of protein-protein interactions for further experimental identification of HCV protein complexes. The method can be used to analyse other viral genomes and to predict the associated protein interaction networks. PMID- 27198622 TI - The 2002 Chandigarh cholera outbreak revisited: utility of MALDI-TOF as a molecular epidemiology tool. AB - In July 2002, an outbreak of cholera occurred in north India with two separate geographical foci. Pulsed field gel electrophoresis (PFGE) was previously used in typing a representative sample of these isolates. This study evaluates the usefulness of MALDI-TOF as an epidemiological tool for typing Vibrio cholerae isolates in comparison with PFGE and Amplified fragment length polymorphisms (AFLP). Forty-six isolates of V. cholerae isolated from stool of patients affected in the July 2002 outbreak were typed using MALDI-TOF. To validate its utility, clinical and environmental isolates previously characterized by PFGE and AFLP were included for dendrogram analysis. All 46 isolates were correctly identified by MALDI-TOF to species level. Two distinct clades appeared on dendrogram using MALDI-TOF corresponding to the two geographical foci of the outbreak. For the study of evolution of organisms from environment, AFLP was superior as it clearly demarcated clinical and environmental isolates. The outbreak was not due to a single clone but due to multiple clones circulating simultaneously, as was seen with PFGE also. SIGNIFICANCE AND IMPACT OF THE STUDY: MALDI-TOF appears to be a highly discriminatory, cost-effective and rapid epidemiological typing technique that can be used in the investigation of cholera outbreaks. PMID- 27198624 TI - Using historical ecology to reassess the conservation status of coniferous forests in Central Europe. AB - Forests cover approximately one-third of Central Europe. Oak (Quercus) and European beech (Fagus sylvatica) are considered the natural dominants at low and middle elevations, respectively. Many coniferous forests (especially of Picea abies) occur primarily at midelevations, but these are thought to have resulted from forestry plantations planted over the past 200 years. Nature conservation and forestry policy seek to promote broadleaved trees over conifers. However, there are discrepancies between conservation guidelines (included in Natura 2000) and historical and palaeoecological data with regard to the distribution of conifers. Our aim was to bring new evidence to the debate on the conservation of conifers versus broadleaved trees at midelevations in Central Europe. We created a vegetation and land-cover model based on pollen data for a highland area of 11,300 km2 in the Czech Republic and assessed tree species composition in the forests before the onset of modern forestry based on 18th-century archival sources. Conifers dominated the study region throughout the entire Holocene (approximately 40-60% of the area). Broadleaved trees were present in a much smaller area than envisaged by current ideas of natural vegetation. Rather than casting doubt on the principles of Central European nature conservation in general, our results highlight the necessity of detailed regional investigations and the importance of historical data in challenging established notions on the natural distribution of tree species. PMID- 27198625 TI - Evaluating renal function and age as predictors of amikacin clearance in neonates: model-based analysis and optimal dosing strategies. AB - AIMS: We aimed to compare the performance of renal function and age as predictors of inter-individual variability (IIV) in clearance of amikacin in neonates through parallel development of population pharmacokinetic (PK) models and their associated impact on optimal dosing regimens. METHODS: Amikacin concentrations were retrospectively collected for 149 neonates receiving amikacin (post-natal age (PNA) between 4-89 days). Two population PK models were developed in parallel, considering at least as predictors current body weight (WT), in combination with either creatinine clearance (CLcr ) or age descriptors. Using stochastic simulations for both renal function or age-based dosing, we identified optimal dosing strategies that were based on attainment of optimal peak- (PCC) and trough target concentration coverage (TCC) windows associated with efficacy and toxicity. RESULTS: The CLcr and age-based population PK models both included current body weight (WT) on CL, central distribution volume and intercompartmental clearance, in combination with either CLcr or PNA as predictors for IIV of clearance (CL). The WT-CLcr model explained 6.9% more IIV in CL compared with the WT-PNA model. Both models successfully described an external dataset (n = 53) of amikacin PK. The simulation analysis of optimal dose regimens suggested similar performance of either CLcr or PNA based dosing. CONCLUSION: CLcr predicted more IIV in CL, but did not translate into clinically relevant improvements of target concentrations. Our optimized dose regimens can be considered for further evaluation to optimize initial treatment with amikacin. PMID- 27198626 TI - Improvement of beta-Carotene Bioaccessibility from Dietary Supplements Using Excipient Nanoemulsions. AB - The influence of excipient nanoemulsions on beta-carotene bioaccessibility from commercial dietary supplements (tablets or soft gels) was studied employing an in vitro gastrointestinal tract (GIT) model. Excipient nanoemulsions were formulated from long or medium chain triglycerides (LCT or MCT) to determine the impact of lipid type on carotenoid bioaccessibility. Dietary supplements were tested using the GIT model in the absence or presence of excipient nanoemulsions. beta carotene bioaccessibility from tablets (0.3%) or soft gels (2.4%) was low when tested in isolation. LCT nanoemulsions greatly improved beta-carotene bioaccessibility from tablets (20%) and slightly improved it from soft gels (5%), whereas MCT nanoemulsions only slightly improved bioaccessibility. These results were attributed to the ability of large carotenoid molecules to be incorporated into large mixed micelles formed by LCT digestion but not by small ones formed by MCT digestion. Our results indicate that excipient nanoemulsions have considerable potential for improving nutraceutical bioavailability from dietary supplements. PMID- 27198627 TI - Reply to Letter to the Editor regarding anaplastic thyroid carcinoma. PMID- 27198628 TI - No microplastics in benthic eelpout (Zoarces viviparus): An urgent need for spectroscopic analyses in microplastic detection. AB - Monitoring the ingestion of microplastics is challenging and suitable detection techniques are insufficiently used. Thus, misidentifying natural for synthetic microfibres cannot be avoided. As part of a framework to monitor the ingestion of microplastics in eelpout, this short report addresses the accurate identification of microfibres. We show that, following visual inspections, putatively synthetic microfibres are indeed of natural origin, as ascertained by spectrometric analyses. Consequently, we call for an inclusion of spectroscopic techniques in standardized microplastic monitoring schemes. PMID- 27198629 TI - Antibiotics versus no treatment for toxoplasma retinochoroiditis. AB - BACKGROUND: Acute toxoplasma retinochoroiditis causes transient symptoms of ocular discomfort and may lead to permanent visual loss. Antibiotic treatment aims primarily to reduce the risk of permanent visual loss, recurrent retinochoroiditis, and the severity and duration of acute symptoms. There is uncertainty about the effectiveness of antibiotic treatment. OBJECTIVES: To compare the effects of antibiotic treatment versus placebo or no treatment for toxoplasma retinochoroiditis. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision group Trials Register) (2016, Issue 1), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to February 2016), EMBASE (January 1980 to February 2016), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to February 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 22 February 2016. We searched the reference lists of identified articles and contacted pharmaceutical companies for unpublished trials. SELECTION CRITERIA: We included randomised controlled trials that compared any antibiotic treatment against placebo or no treatment. We excluded trials that included immunocompromised participants. We considered any antibiotic treatment known to be active against Toxoplasma gondii. Antibiotic treatment could be given in any dose orally, by intramuscular injection, by intravenous infusion, or by intravitreal injection. DATA COLLECTION AND ANALYSIS: The primary outcomes for this review were visual acuity at least three months after treatment and risk of recurrent retinochoroiditis. Secondary outcomes were improvement in symptoms and signs of intraocular inflammation, size of lesion, and adverse events. We used standard methodological procedures expected by Cochrane. MAIN RESULTS: Four trials that randomised a total of 268 participants met the inclusion criteria. In all four studies antibiotic was administered orally.One study conducted in Brazil in both adults and children compared trimethoprim sulfamexacocol over 20 months to no treatment and was judged to be at high risk of performance, detection, and attrition bias. The other three studies compared antibiotic treatment to placebo. We judged these three studies to be at a mixture of low or unclear risk of bias due to poor reporting. One study conducted in the US in adults studied pyrimethamine-trisulfapyrimidine for eight weeks; one study conducted in the UK in children and adults evaluated pyrimethamine for four weeks; and one study conducted in Brazil in adults investigated trimethoprim sulfamethoxazole for 12 months. In the last study, all participants had active retinochoroiditis and were treated with antibiotics for 45 days prior to randomisation to trimethoprim-sulfamethoxazole versus placebo.Only the study in Brazil of trimethoprim-sulfamethoxazole over 12 months, in participants with healed lesions, reported the effect of treatment on visual acuity. People treated with antibiotics may have a similar change in visual acuity compared with people treated with placebo at one year (mean difference -1.00 letters, 95% confidence interval (CI) -7.93 to 5.93 letters; 93 participants; low-quality evidence).Treatment with antibiotics probably reduces the risk of recurrent retinochoroiditis compared with placebo (risk ratio (RR) 0.26, 95% CI 0.11 to 0.63; 227 participants; 3 studies; I(2) = 0%; moderate-quality evidence); similar results were seen for acute and chronic retinochoroiditis.The UK study of pyrimethamine for four weeks reported an improvement in intraocular inflammation in treated compared with control participants (RR 1.76, 95% CI 0.98 to 3.19; 29 participants; low-quality evidence). The study in Brazil of trimethoprim sulfamethoxazole for 12 months stated that the severity of inflammation was higher in the comparator group when compared to the antibiotic-treated group but did not provide further details. In the US study of pyrimethamine trisulfapyrimidine for eight weeks intraocular inflammation had almost completely resolved by eight weeks in all participants, however in this study all participants received steroid treatment.Two studies (UK and US studies) reported an increased risk of adverse events in treated participants. These were a fall in haemoglobin, leucocyte, and platelet count, nausea, loss of appetite, rash, and arthralgia. AUTHORS' CONCLUSIONS: Treatment with antibiotics probably reduces the risk of recurrent toxoplasma retinochoroiditis, but there is currently no good evidence that this leads to better visual outcomes. However, absence of evidence of effect is not the same as evidence of no effect. Further trials of people with acute and chronic toxoplasma retinochoroiditis affecting any part of the retina are required to determine the effects of antibiotic treatment on visual outcomes. PMID- 27198630 TI - The Hidden Conformation of Lewis x, a Human Histo-Blood Group Antigen, Is a Determinant for Recognition by Pathogen Lectins. AB - Histo-blood group epitopes are fucosylated branched oligosaccharides with well defined conformations in solution that are recognized by receptors, such as lectins from pathogens. We report here the results of a series of experimental and computational endeavors revealing the unusual distortion of histo-blood group antigens by bacterial and fungal lectins. The Lewis x trisaccharide adopts a rigid closed conformation in solution, while crystallography and molecular dynamics reveal several higher energy open conformations when bound to the Ralstonia solanacearum lectin, which is in agreement with thermodynamic and kinetic measurements. Extensive molecular dynamics simulations confirm rare transient Le(x) openings in solution, frequently assisted by distortion of the central N-acetyl-glucosamine ring. Additional directed molecular dynamic trajectories revealed the role of a conserved tryptophan residue in guiding the fucose into the binding site. Our findings show that conformational adaptation of oligosaccharides is of paramount importance in cell recognition and should be considered when designing anti-infective glyco-compounds. PMID- 27198631 TI - Cause of death in patients with chronic visceral and chronic neurovisceral acid sphingomyelinase deficiency (Niemann-Pick disease type B and B variant): Literature review and report of new cases. AB - BACKGROUND: Acid sphingomyelinase deficiency (ASMD), [Niemann-Pick Disease Types A and B (NPD A and B)], is an inherited metabolic disorder resulting from deficiency of the lysosomal enzyme acid sphingomyelinase. Accumulation of sphingomyelin in hepatocytes, reticuloendothelial cells, and in some cases neurons, results in a progressive multisystem disease that encompasses a broad clinical spectrum of neurological and visceral involvement, including: infantile neurovisceral ASMD (NPD A) that is uniformly fatal by 3years of age; chronic neurovisceral ASMD (intermediate NPD A/B; NPD B variant) that has later symptom onset and slower neurological and visceral disease progression; and chronic visceral ASMD (NPD B) that lacks neurological symptoms but has significant disease-related morbidities in multiple organ systems. The purpose of this study was to characterize disease-related morbidities and causes of death in patients with the chronic visceral and chronic neurovisceral forms of ASMD. METHODS: Data for 85 patients who had died or received liver transplant were collected by treating physicians (n=27), or abstracted from previously published case studies (n=58). Ages at symptom onset, diagnosis, and death; cause of death; organ involvement, and morbidity were analyzed. RESULTS: Common disease-related morbidities included splenomegaly (96.6%), hepatomegaly (91.4%), liver dysfunction (82.6%), and pulmonary disease (75.0%). The overall leading causes of death were respiratory failure and liver failure (27.7% each) irrespective of age. For patients with chronic neurovisceral ASMD (31.8%), progression of neurodegenerative disease was a leading cause of death along with respiratory disease (both 23.1%) and liver disease (19.2%). Patients with chronic neurovisceral disease died at younger ages than those with chronic visceral disease (median age at death 8 vs. 23.5years). CONCLUSIONS: The analysis emphasizes that treatment goals for patients with chronic visceral and chronic neurovisceral ASMD should include reducing splenomegaly and improving liver function and respiratory status, with the ultimate goal of decreasing serious morbidity and mortality. PMID- 27198633 TI - Enhanced surveillance of a lymphogranuloma venereum outbreak in Sydney 2010-2012. AB - OBJECTIVES: To investigate an increase in lymphogranuloma venereum (LGV) notifications in New South Wales (NSW). METHODS: Enhanced surveillance of notified LGV cases in NSW between May 2010 and April 2012 using doctor and patient questionnaires. RESULTS: Thirty-seven doctors who had diagnosed 67 (76%) of 88 notified anorectal LGV infections were interviewed. The majority (n=33, 89%) of treating doctors were formally trained and accredited in HIV management and prescribing, and most (n=32, 86%) worked in a public sexual health clinic or a general practice with a high caseload of men who have sex with men (MSM). All 67 cases were MSM who resided in inner-city Sydney and all were serovar L2b. Anal symptoms had been present in 64 cases (96%, 95%CI 87-99%) for a median of 8 days (range 2-1,825) prior to presentation. Almost one-third (n=20) had another concurrent STI diagnosed. Most (82%) of the 22 interviewed patients reported being HIV positive and having other STIs diagnosed over the past year. In the preceding month, all 22 men reported condomless anal sex and the median number of casual sexual partners was 5 (range 0-100). CONCLUSIONS: Characteristics of LGV cases in NSW are similar to those described worldwide, suggesting that a sexually adventurous subgroup of MSM are at particular risk of infection. IMPLICATIONS: Education of non-sexual-health clinicians on LGV risk factors, presentation, testing and management may allow more timely diagnosis and notification of contacts to reduce LGV transmission in the community. PMID- 27198634 TI - The solubility of nickel and its migration through the cementitious backfill of a geological disposal facility for nuclear waste. AB - This work describes the solubility of nickel under the alkaline conditions anticipated in the near field of a cementitious repository for intermediate level nuclear waste. The measured solubility of Ni in 95%-saturated Ca(OH)2 solution is similar to values obtained in water equilibrated with a bespoke cementitious backfill material, on the order of 5*10(-7)M. Solubility in 0.02M NaOH is one order of magnitude lower. For all solutions, the solubility limiting phase is Ni(OH)2; powder X-ray diffraction and scanning transmission electron microscopy indicate that differences in crystallinity are the likely cause of the lower solubility observed in NaOH. The presence of cellulose degradation products causes an increase in the solubility of Ni by approximately one order of magnitude. The organic compounds significantly increase the rate of Ni transport under advective conditions and show measurable diffusive transport through intact monoliths of the cementitious backfill material. PMID- 27198632 TI - Mechanisms in E. coli and Human Mismatch Repair (Nobel Lecture). AB - DNA molecules are not completely stable, they are subject to chemical or photochemical damage and errors that occur during DNA replication resulting in mismatched base pairs. Through mechanistic studies Paul Modrich showed how replication errors are corrected by strand-directed mismatch repair in Escherichia coli and human cells. PMID- 27198635 TI - Regulation of Genome Architecture and Function by Polycomb Proteins. AB - Polycomb group (PcG) proteins dynamically define cellular identities through the epigenetic repression of key developmental regulatory genes. PcG proteins are recruited to specific regulatory elements to modify the chromatin surrounding them. In addition, they regulate the organization of their target genes in the 3D space of the nucleus, and this regulatory function of the 3D genome architecture is involved in cell differentiation and the maintenance of cellular memory. In this review we discuss recent advances in our understanding of how PcG proteins are recruited to chromatin to induce local and global changes in chromosome conformation and regulate their target genes. PMID- 27198636 TI - Laser peripheral iridotomy changes anterior chamber architecture. AB - PURPOSE: The pressure gradient between anterior and posterior chamber in acute angle closure (AAC) and primary angle closure suspects is balanced by a sufficient laser peripheral iridotomy (LPI). The anterior chamber changes induced by LPI in patients with unilateral AAC were examined and compared to healthy eyes to define threshold values, which may help to discriminate between healthy and diseased eyes. METHODS: Using Scheimpflug photography, anterior chamber depth (ACD), anterior chamber volume (ACV), anterior chamber angle (ACA), and central corneal thickness (CCT) were measured before and after LPI in both eyes of unilateral AAC cases. These measurements were compared to a group of healthy control eyes to determine threshold values for ACD, ACV, and ACA. RESULTS: The ACD, ACV, and ACA increased significantly in the 25 AAC eyes after LPI. The ACD, ACV, ACA, and CCT values in the AAC eyes obtained before LPI were compared to a control group of 59 healthy eyes with wide open chamber angles. The cutoff values revealed by receiver operating characteristic analysis were 2.1 mm for ACD, 90.5 mm2 for ACV, and 27.25 degrees for ACA. CONCLUSIONS: Our results confirm the significant changes of the anterior segments architecture induced by LPI in AAC eyes. The found threshold values for ACD, ACV, and ACA may help in daily clinical routine to discriminate between healthy eyes and those in need for a prophylactic LPI. PMID- 27198637 TI - Decreased hyaluronan concentration during primary rhegmatogenous retinal detachment. AB - PURPOSE: To evaluate the concentration and molecular weight of hyaluronan (HA) polysaccharides as well as hyaluronidase activity in patients with rhegmatogenous retinal detachment (RRD). METHODS: Twenty vitreous samples from 20 patients with RRD and 19 samples from 19 patients with idiopathic epiretinal membrane, macular hole, or vitreomacular traction syndrome were collected during surgical management with pars plana vitrectomy. The molecular weight of various HA fragments was assessed using agarose gel electrophoresis. Enzyme-linked immunosorbent assay was employed for the measurement of HA (in MUg/mL). Hyaluronidase activity was evaluated using substrate (HA) sodium dodecyl sulfate polyacrylamide gel electrophoresis. RESULTS: Agarose gel electrophoresis showed that the vitreous of the control group contained HA of high molecular mass, in contrast with the patient group. Mean HA concentration in the patient group was 50.96 MUg/mL and differed significantly from that of the control group, which was 271.81 MUg/mL (p<0.0005). Hyaluronidase activity was significantly higher in the vitreous of patients with RRD (p = 0.037). CONCLUSIONS: The vitreous of patients with RRD is characterized by decreased HA concentration compared to controls of the same age and sex and shows higher hyaluronidase catalytic activity. Hyaluronan degradation could be associated with specific vitreous alterations that potentially contribute to retinal break formation and consequently detachment. PMID- 27198639 TI - Impact of Introducing 2 Simple Technique Modifications on the Descemet Membrane Endothelial Keratoplasty Learning Curve. AB - Purpose To analyze the impact of performing premarking of the Descemet roll and using SF6 20% on a surgeon's Descemet membrane endothelial keratoplasty (DMEK) learning process. Methods A total of 30 consecutive eyes with endothelial dysfunction undergoing DMEK during the learning curve of a surgeon were retrospectively analyzed. Prior to the study, the surgeon had already performed 10 DMEKs. The first 15 consecutive patients were included in group 1 (no premarking and air tamponade) and the other 15 consecutive patients were included in group 2 (premarking and SF6 tamponade). Main outcome parameters were best corrected visual acuity (BCVA), endothelial cell density (ECD) loss at 6 months, and intraoperative and postoperative complications. Results Among the 2 groups, BCVA and ECD loss at 6 months were similar. However, there was a statistically significant reduction in primary graft failure (40% vs 0%) and need of rebubbling due to complete or partial graft detachment (40% vs 6%) when comparing group 1 versus group 2. In group 1, half of the patients needing rebubbling had primary graft failure. Conclusions Based on our personal experience, premarking the graft to assess orientation and using a SF6 gas tamponade dramatically reduces the risk of primary graft failure and the need for rebubbling even during the first stages of the learning curve. These findings should encourage surgeons to safely change from Descemet stripping automated endothelial keratoplasty to DMEK. PMID- 27198638 TI - Anterior lamina cribrosa surface position in idiopathic intracranial hypertension and glaucoma. AB - PURPOSE: To compare the anterior lamina cribrosa (LC) surface position in patients with idiopathic intracranial hypertension (IIH), primary open-angle glaucoma (high-tension glaucoma [HTG] and normal-tension glaucoma [NTG]), and healthy controls using enhanced depth imaging spectral-domain optical coherence tomography (EDI-OCT). METHODS: This was a retrospective, cross-sectional observational study of 11 eyes with IIH, 20 eyes with HTG, 20 eyes with NTG, and 37 control eyes. Serial horizontal B-scans of the optic nerve head were obtained using EDI-OCT. The LC depth, defined as the distance from the Bruch membrane opening plane to the anterior LC surface, was manually measured on selected B scans covering the central three-quarters of the optic nerve head in each eye. RESULTS: Mean LC depth in patients with IIH (325.2 +/- 92.1 um) was significantly (p<0.01) decreased compared to control subjects (387.8 +/- 53.9 um). In HTG, the mean LC depth (493.0 +/- 115.2 um) was significantly increased compared to NTG (376.6 +/- 27.1 um, p<0.05) and control subjects (332.7 +/- 53.1 um, p<0.001). The trans-LC pressure difference (TLPD) (intraocular pressure - cerebrospinal fluid pressure) was positively correlated with the LC depth (r = 0.96, p<0.001) and inversely correlated with visual field perimetric mean deviation in patients with IIH (r = -0.88, p<0.001). CONCLUSIONS: The LC is positioned anteriorly in patients with IIH and posteriorly in glaucomatous eyes compared to normal controls. The positional changes of the LC could be a result of the TLPD between the intraocular and intracranial pressure compartments. PMID- 27198640 TI - Rod function in diabetic patients without and with early diabetic retinopathy. AB - PURPOSE: To compare rod function among diabetic patients without and with mild nonproliferative diabetic retinopathy (DR) and healthy controls by means of scotopic microperimetry and dark-adapted electroretinography. METHODS: Sixty-one diabetic patients and 30 age-matched controls (control group) underwent complete ophthalmic examination, scotopic microperimetry, and dark-adapted 0.01 electroretinography (DA-ERG). RESULTS: In 32 eyes, DR was absent (no-DR group); in 29 eyes, only microaneurysms were observed (DR group). No statistically significant differences in fixation stability, fixation location, or scotopic sensitivity among the 3 groups were observed. Implicit time and amplitude of the DA-ERG b-wave of no-DR and DR groups were not different from controls. Scotopic microperimetry showed a dense scotoma centered onto the fovea in all subjects, consistent with the rod-free zone. Greater scotopic sensitivity was found in a ring located 8 degrees from the fovea (9.33 +/- 1.33 dB). CONCLUSIONS: Diabetic patients without DR and with mild nonproliferative DR did not show alterations in rod-based function, as examined by microperimetry and confirmed by DA-ERG. Scotopic microperimetry measures rod-based function and offers additional information in the evaluation of the aspects of involvement of retinal cells in diabetes. PMID- 27198641 TI - Comparison of macular findings due to vitreomacular traction alone or in association with epiretinal membrane. AB - PURPOSE: To evaluate the anatomical and functional findings in patients with vitreomacular traction (VMT) alone or in combination with epiretinal membrane (ERM). METHODS: In this retrospective, cross-sectional study, we studied 102 patients with VMT, either alone (n = 37) or combined with ERM (n = 65). All patients were examined with spectral-domain optical coherence tomography (SD OCT). We recorded the vitreofoveal angle of VMT nasally and temporally, the horizontal diameter of VMT, macular thickness, the presence, type, and location of macular edema, the ellipsoid zone (EpsilonZeta)/external limiting membrane (ELM) status, and the visual acuity. RESULTS: Patients with VMT combined with ERM presented smaller vitreofoveal angle nasally and temporally, broader adhesion diameter, and a greater extent of EZ defect compared to patients with VMT alone, although there was no statistically significant difference in EZ and ELM condition regarding the number of affected cases. There is also no statistically significant difference between the 2 groups concerning the visual acuity. In the majority of patients with VMT alone, cystoid macular edema was present mainly at the foveal area. In cases where VMT coexisted with ERM, macular edema was mostly found to be diffuse, while cystoid or mixed type, extending to the whole macular area, was also present. CONCLUSIONS: Patients with VMT in association with ERM have different characteristics in SD-OCT compared to those with VMT alone regarding the type and location of macular edema, the extent of EZ defect, as well as the vitreofoveal angle and the VMT diameter. Moreover, they presented worse visual acuity compared to those with VMT alone, although the difference did not reach statistical significance. PMID- 27198642 TI - Prediction of the development of late enophthalmos in pure blowout fractures: delayed orbital tissue atrophy plays a major role. AB - PURPOSE: To retrospectively evaluate the risk factors for the development of late enophthalmos in pure blowout fractures. METHODS: We reviewed 49 cases of pure blowout fractures diagnosed in Ajou University Hospital, South Korea, from January 2005 to June 2015. We assumed that several factors influence the development of late enophthalmos, including bony defect size, volume of displaced soft tissue, number of fracture sites, involvement of floor, soft tissue incarceration through the bony defect, and patient age. RESULTS: Twenty-one patients were diagnosed with late enophthalmos (group 1) while 28 patients were not (group 2). Soft tissue incarceration, presumably causing the soft tissue injury, was the only factor that increased the risk for late enophthalmos in this study (p = 0.04, odds ratio 4.5). In contrast with previous studies, there were no meaningful correlation between bony defect size or volume of displaced soft tissue and development of late enophthalmos. Number of fracture sites, involvement of floor, and patient age did not increase the risk for late enophthalmos. CONCLUSIONS: We suggest that the delayed orbital tissue atrophy due to soft tissue injury plays a more important role than other hypotheses in the development of late enophthalmos. It is necessary to overcorrect to some extent if there is soft tissue incarceration through the bony defect in the initial computed tomography, and clinicians should warn patients about the development of late enophthalmos despite orbital reconstructive surgery. PMID- 27198643 TI - Novel multi-functional europium-doped gadolinium oxide nanoparticle aerosols facilitate the study of deposition in the developing rat lung. AB - Ambient ultrafine particulate matter (UPM), less than 100 nm in size, has been linked to the development and exacerbation of pulmonary diseases. Age differences in susceptibility to UPM may be due to a difference in delivered dose as well as age-dependent differences in lung biology and clearance. In this study, we developed and characterized aerosol exposures to novel metal oxide nanoparticles containing lanthanides to study particle deposition in the developing postnatal rat lung. Neonatal, juvenile and adult rats (1, 3 and 12 weeks old) were nose only exposed to 380 MUg m(-3) of ~30 nm europium doped gadolinium oxide nanoparticles (Gd2O3:Eu(3+)) for 1 h. The deposited dose in the nose, extrapulmonary airways and lungs was determined using inductively-coupled plasma mass spectroscopy. The dose of deposited particles was significantly greater in the juvenile rats at 2.22 ng per g body weight compared to 1.47 ng per g and 0.097 ng per g for the adult and neonate rats, respectively. Toxicity was investigated in bronchoalveolar lavage fluid (BALF) by quantifying recovered cell types, and measuring lactate dehydrogenase activity and total protein. The toxicity data suggests that the lanthanide particles were not acutely toxic or inflammatory with no increase in neutrophils or lactate dehydrogenase activity at any age. Juvenile and adult rats had the same mass of deposited NPs per gram of lung tissue, while neonatal rats had significantly less NPs deposited per gram of lung tissue. The current study demonstrates the utility of novel lanthanide-based nanoparticles to study inhaled particle deposition in vivo and has important implications for nanoparticles delivery to the developing lung either as therapies or as a portion of particulate matter air pollution. PMID- 27198645 TI - Doubling down on phosphorylation as a variable peptide modification. AB - Some mass spectrometrists believe that searching for variable PTMs like phosphorylation of serine or threonine when using database-search algorithms to interpret peptide tandem mass spectra will increase false-positive matching. The basis for this is the premise that the algorithm compares a spectrum to both a nonphosphorylated peptide candidate and a phosphorylated candidate, which is double the number of candidates compared to a search with no possible phosphorylation. Hence, if the search space doubles, false-positive matching could increase accordingly as the algorithm considers more candidates to which false matches could be made. In this study, it is shown that the search for variable phosphoserine and phosphothreonine modifications does not always double the search space or unduly impinge upon the FDR. A breakdown of how one popular database-search algorithm deals with variable phosphorylation is presented. PMID- 27198644 TI - Siblings of children with complex care needs: their perspectives and experiences of participating in everyday life. AB - BACKGROUND: Participating in everyday life is essential to the healthy development and emotional well-being of children. However, little is known about siblings of children with complex care needs (CCN), and their perspectives and experiences of participating in everyday life. The aim of this paper is to present research findings that add to our understanding of how siblings of children with CCN view and experience participation in everyday life. METHODS: To arrive at a detailed and accurate understanding of the siblings' perspectives and experiences, we used the qualitative research design of ethnography. Sixteen siblings (seven brothers, nine sisters) of children with CCN were recruited. The siblings ranged in age between 7 and 25 years, with a mean age of 14 years. All siblings took part in opened-ended interviews and completed ecomaps to describe how they participate. Five siblings also took part in the photovoice method. Analysis involved several iterative steps, congruent with ethnography. RESULTS: Four main themes emerged as follows: (1) participation is about being part of a group; (2) it feels good; (3) I love my sibling but...; and (4) promoting participation. Siblings of children with CCN identified challenges to participation and also described ways that they participate that relate to the care of their sibling. CONCLUSIONS: Siblings prioritized the relationship with their sisters and brothers with CCN in their life, and a great deal of their participation was chosen with their sibling in mind. Sibling-to-sibling relationships were distinct and meaningful and, as a result, participation was always done mindfully and with the family needs at the forefront. Nonetheless, clinicians caring for children with CCN must keep in mind the challenges that siblings of children with CCN experience and provide strategies to siblings that will help to promote their participation in everyday life. PMID- 27198646 TI - Medical humanitarianism: ethnographies of practice. PMID- 27198647 TI - Author's reply. PMID- 27198648 TI - Interobserver agreement on the echocardiographic parameters that estimate right ventricular systolic function in the early postoperative period of cardiac surgery. AB - PRIMARY OBJECTIVE: To know the variability of transthoracic echocardiographic parameters that assess right ventricular systolic function by analyzing interobserver agreement in the early postoperative period of cardiovascular surgery. SECONDARY OBJECTIVE: To assess the feasibility of these echocardiographic measurements. DESIGN: A cross-sectional study, double-blind pilot study was carried out from May 2011 to February 2013. SETTING: Cardiovascular postoperative critical care at the National Institute of Cardiology "Ignacio Chavez", Mexico City, Mexico. PATIENTS: Consecutive, non probabilistic sampling. Fifty-six patients were studied in the postoperative period of cardiac surgery. INTERVENTION: The first echocardiographic parameters were obtained between 6-8hours after cardiac surgery, followed by blinded second measurements. MAIN VARIABLES: Tricuspid annular plane systolic excursion (TAPSE), tricuspid annular peak systolic velocity on tissue Doppler imaging (VSPAT), diameters and right ventricular outflow area, tract fractional shortening. The agreement was analyzed by the Bland-Altman method, and its magnitude was assessed by the intraclass correlation coefficient (95% confidence interval). RESULTS: Both observers evaluated TAPSE and VSPAT in 48 patients (92%). The average TAPSE was 11.68+/-4.53mm (range 4-27mm). Right ventricular systolic dysfunction was observed in 41 cases (85%) and normal TAPSE in 7 patients (15%). The average difference and its limits according to TAPSE were -0.917+/-2.95 (-6.821, 4.988), with a magnitude of 0.725 (0.552, 0.837); the tricuspid annular peak systolic velocity on tissue Doppler imaging was -0.001+/-0.015 (-0.031, 0.030), and its magnitude 0.825 (0.708, 0.898), respectively. CONCLUSIONS: VSPAT and TAPSE were estimated by both observers in 92% of the patients, these parameters exhibiting the lowest interobserver variability. PMID- 27198649 TI - Points, skyrmions and torons in chiral nematic droplets. AB - Chiral nematic droplets with perpendicular surface alignment of liquid crystalline molecules frustrate the helical structure into convoluted 3D textures with complex topology. We observe the droplets with fluorescent confocal polarising microscopy (FCPM), and reconstruct and analyse for the first time the topology of the 3D director field using a novel method of director reconstruction from raw data. We always find an odd number of topological defects, which preserve the total topological charge of the droplet of +1 regardless of chirality. At higher chirality, we observe up to 5 point hedgehog defects, which are elastically stabilized with convoluted twisted structures, reminiscent of 2D skyrmions and toron-like structure, nested into a sphere. PMID- 27198650 TI - The synergy between the insect-inspired claws and adhesive pads increases the attachment ability on various rough surfaces. AB - To attach reliably on various inclined rough surfaces, many insects have evolved both claws and adhesive pads on their feet. However, the interaction between these organs still remains unclear. Here we designed an artificial attachment device, which mimics the structure and function of claws and adhesive pads, and tested it on stiff spheres of different dimensions. The results show that the attachment forces of claws decrease with an increase of the sphere radius. The forces may become very strong, when the sphere radius is smaller or comparable to the claw radius, because of the frictional self-lock. On the other hand, adhesive pads generate considerable adhesion on large sphere diameter due to large contact areas. The synergy effect between the claws and adhesive pads leads to much stronger attachment forces, if compared to the action of claw or adhesive pads independently (or even to the sum of both). The results carried out by our insect inspired artificial attachment device clearly demonstrate why biological evolution employed two attachment organs working in concert. The results may greatly inspire the robot design, to obtain reliable attachment forces on various substrates. PMID- 27198651 TI - Multicriteria assessment of advanced treatment technologies for micropollutants removal at large-scale applications. AB - With the introduction and discharge of thousands of new micropollutants (MPs) every year, traditional water and wastewater treatment plants may be incapable of tackling them all. With their low concentrations and diversity in nature, MP removal encounters numerous challenges. Although some MPs are effectively eliminated via conventional treatment methods, most of them can easily escape and are retained in the discharged effluent. Therefore, advanced methods such as (i) adsorption, (ii) oxidation and advanced oxidation processes (O3 and O3-based advanced oxidation processes, UV/H2O2), (iii) membrane processes, and (iv) membrane bioreactors, become an inevitable approach. Despite the unsurprisingly vast number of papers on MP treatment available at present, most of these studies were carried out at a laboratory scale while only a few pilot- and full-scale studies have experimented. Nevertheless, an in-depth assessment of real-world MP treatment methods is extremely crucial for practitioners. To date, no paper has been dedicated to look at this issue. Therefore, this paper aims to review these large-scale treatment methods. First, the paper goes through the regulations and standards which deal with MPs in water courses. It will then assess these methods in various case-studies with reference to different criteria towards serving as a reference for further practical applications. PMID- 27198653 TI - Why there is no supernatural morality: response to Miller's opening statement. AB - If one is going to argue that objective morality depends on an Archimedean point outside the natural world, then it would seem to imply that this source is necessarily supernatural. Thus, Christian Miller begins by defining precisely who he thinks this supernatural moral law giver is: the omniscient, omnipotent, and omnibenevolent creator of the universe who is still actively involved with human affairs-Elohim, Jehovah, Yahweh, or Allah-aka God. Already I'm skeptical. PMID- 27198652 TI - Home-Based Exercise Training Improves Left Ventricle Diastolic Function in Survivors of Childhood ALL: A Tissue Doppler and Velocity Vector Imaging Study. AB - BACKGROUND: Advanced echocardiographic methods may reveal signs of late anthracycline cardiac toxicity (ACT) even in asymptomatic patients. We studied echocardiographic tissue Doppler imaging (TDI) and velocity vector imaging (VVI) in long-term survivors of childhood acute lymphoblastic leukemia (ALL) before and after an exercise intervention. METHODS: Twenty-one asymptomatic, anthracycline treated, long-term childhood ALL survivors with matched controls were studied at baseline. Seventeen of the survivors participated in a 3-month home-based exercise program. Echocardiography with TDI and VVI was performed. RESULTS: At baseline, ejection fraction (60.7 +/- 4.7% vs. 62.3 +/- 3.7%, P = 0.22) and fractional shortening (32.6 +/- 3.1% vs. 34.0 +/- 2.8%, P = 0.13) were similar in survivors and controls. Lateral early diastolic mitral annulus velocity E' (32.81 +/- 5.71 cm/sec vs. 38.03 +/- 6.21 cm/sec, P = 0.01), E'/A' (1.60 +/- 0.48 vs. 2.07 +/- 0.63, P = 0.01), and E/E' (2.78 +/- 0.35 vs. 2.42 +/- 0.62, P = 0.04) were impaired compared to controls. Peak circumferential strain and strain rate were attenuated at apex (-24.50 +/- 3.46% vs. -28.06 +/- 4.39%, P = 0.01 and 1.47 +/- 0.22 sec(-1) vs. -1.68 +/- 0.33 sec(-1) , P = 0.02) compared to controls. After the intervention, early diastolic mitral inflow velocity E (87.76 +/- 12.54 cm/s vs. 95.28 +/- 10.48 cm/s, P = 0.04) and E' increased (31.78 +/- 5.50 cm/s vs. 34.96 +/- 5.41 cm/s, P < 0.01). Peak circumferential systolic and diastolic strain rates at mid-level (-1.22 +/- 0.21 sec(-1) vs. -1.35 +/- 0.24 sec(-1) , P = 0.04 and 1.25 +/- 0.25 sec(-1) vs. 1.48 +/- 0.35 sec(-1) , P < 0.01) improved after the exercise program. CONCLUSIONS: A simple home-based exercise program improved cardiac function in asymptomatic childhood ALL survivors. Adding TDI in routine echocardiographic examination may improve the recognition of early signs of ACT, and VVI may bring additional information. The improvements in cardiac function after the exercise program emphasize the importance of physical activity in this population. PMID- 27198654 TI - Elucidating dominant pathways of the nano-particle self-assembly process. AB - Self-assembly processes play a key role in the fabrication of functional nano structures with widespread application in drug delivery and micro-reactors. In addition to the thermodynamics, the kinetics of the self-assembled nano structures also play an important role in determining the formed structures. However, as the self-assembly process is often highly heterogeneous, systematic elucidation of the dominant kinetic pathways of self-assembly is challenging. Here, based on mass flow, we developed a new method for the construction of kinetic network models and applied it to identify the dominant kinetic pathways for the self-assembly of star-like block copolymers. We found that the dominant pathways are controlled by two competing kinetic parameters: the encounter time Te, characterizing the frequency of collision and the transition time Tt for the aggregate morphology change from rod to sphere. Interestingly, two distinct self assembly mechanisms, diffusion of an individual copolymer into the aggregate core and membrane closure, both appear at different stages (with different values of Tt) of a single self-assembly process. In particular, the diffusion mechanism dominates the middle-sized semi-vesicle formation stage (with large Tt), while the membrane closure mechanism dominates the large-sized vesicle formation stage (with small Tt). Through the rational design of the hydrophibicity of the copolymer, we successfully tuned the transition time Tt and altered the dominant self-assembly pathways. PMID- 27198656 TI - Comment on: "Analysis of Silicones Released from Household Items and Baby Articles by Direct Analysis in Real Time-Mass Spectrometry" by Jurgen H. Gross. J. Am. Soc. Mass Spectrom. 26, 511-521 (2015). PMID- 27198655 TI - Central nervous system relapse in patients with untreated HER2-positive esophageal or gastroesophageal junction adenocarcinoma. AB - Although HER2-positive breast cancers demonstrate a propensity for central nervous system (CNS) metastasis, it is unknown whether other HER2-positive tumors, including adenocarcinomas of the esophagus/gastroesophageal junction (EAC), share this characteristic. Insight into this association may inform the development of HER2-targeted therapies that penetrate the blood-brain barrier. We examined HER2 overexpression and gene amplification in 708 patients with EAC who underwent curative-intent surgery during a time period (1980-1997) when no patient received HER2-targeted therapy. We identified patients whose site of first cancer recurrence was CNS and those who had a CNS relapse at any time. After a median follow-up of 61.2 months, 3.4% (24/708) of patients developed CNS relapse (all involved the brain). Patients with HER2-positive (vs -negative) primary tumors showed a higher 5-year cumulative incidence of CNS relapse as first recurrence (5.8% vs. 1.2%; p = 0.0058) and at any time (8.3% vs. 2.4%; p = 0.0062). In a multivariable model that included covariates previously associated with HER2 or with CNS relapse in breast cancer, HER2 positivity was the only variable that was statistically significantly associated with shorter time to CNS relapse as first recurrence (p = 0.0026) or at any time (hazard ratio 4.3 [95% confidence interval 1.8 to 10.3]; p = 0.001). These are the first data in a non breast cancer to demonstrate an association between HER2 positivity and higher CNS relapse risk after surgery, and suggest that HER2-positive EACs have a predilection for CNS metastases. PMID- 27198657 TI - Halomarina salina sp. nov., isolated from a marine solar saltern. AB - A halophilic archaeal strain, designated ZS-57-S(T), was isolated from Zhoushan marine solar saltern, China. Cells were observed to be pleomorphic, stained Gram negative and formed red pigmented colonies on agar plates. Optimal growth was obtained at 3.9 M NaCl (range 1.4-4.8 M), 0.3 M MgCl2 (range 0-1.0 M), 30 degrees C (range 20-55 degrees C) and pH 6.5-7.5 (range 5.5-9.0). The cells were found to lyse in distilled water and the minimal NaCl concentration to prevent cell lysis was determined to be 5 % (w/v). The major polar lipids were identified as C20C20 and C20C25 diether derivatives of phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester, phosphatidylglycerol sulfate, glucosyl mannosyl glucosyl diether and two unidentified glycolipids. The 16S rRNA gene and rpoB' gene of strain ZS-57-S(T) were phylogenetically related to the corresponding genes of Halomarina oriensis JCM 16495(T) (98.2 and 93.7 % similarities, respectively). The DNA G+C content of strain ZS-57-S(T) was determined to be 67.1 mol% (T m). The phenotypic, chemotaxonomic and phylogenetic properties suggested that strain ZS-57-S(T) (=CGMCC 1.12543(T) = JCM 30039(T)) represents a new species of the genus Halomarina, for which the name Halomarina salina sp. nov. is proposed. PMID- 27198658 TI - No Evidence of Human Polyomavirus 9, WU and KI DNA in Kidney and Urinary Bladder Tumour Tissue Samples. AB - BACKGROUND/AIMS: The oncogenic potential of human polyomaviruses (HPyVs) has been proposed, but so far only Merkel cell carcinoma polyomavirus seems to be associated with a human tumour. The role of BK polyomavirus (BKPyV) in human tumourigenesis remains controversial. BKPyV establishes persistent infection in the urinary tract, and renal and bladder neoplasms have been studied extensively, but conflicting prevalence data are reported. KI, WU and HPyV9 were detected in urine samples suggesting that these viruses may also infect the urinary tract, but their presence in urinary tract tumours has not been studied. The aim of this work was to examine the prevalence of KIPyV, WUPyV, HPyV9 and BKPyV by PCR in renal and bladder neoplasms. METHODS: A total of 190 formalin-fixed paraffin embedded renal neoplasms, bladder cancer and kidney biopsy samples were analysed for the presence of BKPyV, KIPyV, WUPyV and HPyV9 DNA by real-time and nested PCR. RESULTS: Amplifiable DNA was extracted from all the samples, but none of the studied viruses were detected in benign renal neoplasia (0/23), malignant renal tumours (0/89) or bladder cancer (0/76). CONCLUSION: Our study did not find any evidence that BKPyV, KIPyV, WUPyV or HPyV9 are associated with bladder and renal tumours. PMID- 27198659 TI - Preparation of novel butyryl galactose ester-modified coix component microemulsions and evaluation on hepatoma-targeting in vitro and in vivo. AB - The butyryl galactose ester-modified coix component microemulsions (But-Gal-CMEs) was developed for enhanced liver tumor-specific targeting. The study was aimed to evaluate the hepatoma-targeting potential of But-Gal-CMEs in vitro and in vivo. But-Gal-CMEs with a uniform spherical shape exhibited a small particle size (56.68 +/- 0.07 nm), a narrow polydispersity (PDI, 0.144 +/- 0.005) and slightly negative surface charge (-0.102 +/- 0.008 mV). In the cell uptake studies, But Gal-CMEs showed a significant enhancement on the intracellular fluorescent intensity on HepG2 cells model, which was 1.93-fold higher relative to coix component microemulsions (CMEs). The IC50 of But-Gal-CMEs against HepG2 cells was 64.250 MUg/mL, which was notably stronger than that of CMEs. In the cell apoptosis studies, compared with CMEs, But-Gal-CMEs (50 MUg/mL) treatment resulted in a 1.34-fold rise in total apoptosis cells of HepG2. In the biodistribution studies in vivo, the intratumorous fluorescence of Cy5-loaded But Gal-CMEs was 1.43-fold higher relative to that of Cy5-loaded CMEs, suggesting an obviously enhanced accumulation in the tumor sites. Taken as together, But-Gal could be incorporated into the coix component microemulsions as a novel ligand for realizing hepatoma-targeting drugs delivery. PMID- 27198660 TI - Shaping plasticity: Alterations in glutamate transporter localization as a pathophysiological mechanism in severe mental illness. PMID- 27198661 TI - Public-Private Partnerships and Undernutrition: Examples and Future Prospects. AB - In this chapter, we clarify what is meant by public-private partnerships (PPPs), provide examples of both successful and less successful PPPs and describe some broad lessons. We see scope for PPPs that would reduce aspects of undernutrition. However, this optimism comes with significant caveats. First, while there would appear to be a large body of evidence on this topic, closer examination shows that there are few independent, rigorous assessments of the impact of commercial sector engagement in nutrition. Considerable caution is therefore warranted when assessing either commendations or criticisms of PPPs in nutrition. Second, progress in this area requires that the private sector recognize that past and current actions by some firms have created an environment of mistrust and that the public sector accept that sustainable PPPs permit private firms to generate profits. Progress also requires recognition that PPPs involving multiple firms can be problematic either because such partnerships force competitors to collaborate or because they create the potential for the involved firms to lock out firms that are not members of the partnership. Lest this all sound too negative, from a nutrition perspective, we note that there may be significant scope for the involvement of the private sector in driving innovations that could reduce undernutrition. More speculatively, there may also be scope for the private sector to act as a financier of investments to improve children's nutritional status. For PPPs to succeed, there must be open discussions of the objectives, roles and expectations of all parties along with potential conflicts of interest. PMID- 27198663 TI - Chronic skin ulcer following defibrillation. PMID- 27198662 TI - Functional assessment of glioma pathogenesis by in vivo multi-parametric magnetic resonance imaging and in vitro analyses. AB - Gliomas are aggressive brain tumors with poor prognosis. In this study, we report a novel approach combining both in vivo multi-parametric MRI and in vitro cell culture assessments to evaluate the pathogenic development of gliomas. Osteopontin (OPN), a pleiotropic factor, has been implicated in the formation and progression of various human cancers, including gliomas, through its functions in regulating cell proliferation, survival, angiogenesis, and migration. Using rat C6 glioma model, the combined approach successfully monitors the acquisition and decrease of cancer hallmarks. We show that knockdown of the expression of OPN reduces C6 cell proliferation, survival, viability and clonogenicity in vitro, and reduces tumor burden and prolongs animal survival in syngeneic rats. OPN depletion is associated with reduced tumor growth, decreased angiogenesis, and an increase of tumor-associated metabolites, as revealed by T2-weighted images, diffusion-weighted images, K(trans) maps, and 1H-MRS, respectively. These strategies allow us to define an important role of OPN in conferring cancer hallmarks, which can be further applied to assess the functional roles of other candidate genes in glioma. In particular, the non-invasive multi-parametric MRI measurement of cancer hallmarks related to proliferation, angiogenesis and altered metabolism may serve as a useful tool for diagnosis and for patient management. PMID- 27198665 TI - Interactions of Multiple Atmospheric Circulation Drive the Drought in Tarim River Basin. AB - Global warming is likely to cause overall drying of land surfaces and aridity increasing leading to expansion of dry climate zones. There is an increased risk of extremely arid environment and large deserts developed progressively in the central Asia. However, the key factors causing the drying in mid-Asia remain inconclusive. Here, we analyzed the relationship among precipitation, water vapor transportation in Tarim River Basin (TRB) and Multiple Atmospheric Circulation (MAC) to explore the mechanism of MAC driving the drying in TRB, through comparing MAC between abundant and scarce precipitation years. We found that Westerly Circulation (WC) and Asian Summer Monsoon (ASM) are likely to promote the precipitation respectively. Whereas, they not only have their own influence but also restrict each other and facilitate the forming of peculiar water vapor transport channel for TRB, which is probably to restrain the precipitation and its distribution pattern and accelerate the drying in this region. Our results enrich the findings on mechanisms of wet places becoming wetter while dry areas getting drier under the global warming. PMID- 27198664 TI - A phase IIIb study of ledipasvir/sofosbuvir fixed-dose combination tablet in treatment-naive and treatment-experienced Korean patients chronically infected with genotype 1 hepatitis C virus. AB - BACKGROUND: The standard-of-care regimen for chronic hepatitis C virus (HCV) infection in Korea, pegylated-interferon-alpha plus ribavirin, is poorly tolerated. Ledipasvir/sofosbuvir is a two-drug, fixed-dose combination tablet approved in the USA, European Union, and Japan for chronic genotype 1 HCV infection. METHODS: This single-arm, phase IIIb study (NCT02021656) investigated the efficacy and safety of ledipasvir/sofosbuvir fixed-dose combination tablet for 12 weeks in treatment-naive and treatment-experienced Korean patients chronically infected with genotype 1 HCV with or without compensated cirrhosis. RESULTS: The proportion of patients with sustained virologic response 12 weeks after treatment discontinuation (SVR12) was 99 % (92/93), with rates of 100 % (46/46) and 98 % (46/47) in treatment-naive and treatment-experienced patients, respectively. There were no on-treatment failures. One patient relapsed after the end of treatment. The most common treatment-emergent adverse events were headache (8 %, 7/93) and fatigue (6 %, 6/93). There were no grade 3 or 4 adverse events, seven grade 3 laboratory abnormalities, and one premature discontinuation of study treatment (due to nonserious mouth ulceration). None of the three reported serious adverse events were related to treatment. CONCLUSIONS: These data suggest that 12 weeks of ledipasvir/sofosbuvir is effective and well tolerated in treatment-naive and treatment-experienced Korean patients with chronic genotype 1 HCV infection. PMID- 27198666 TI - RIG-like Helicase Regulation of Chitinase 3-like 1 Axis and Pulmonary Metastasis. AB - Chi3l1 is induced by a variety of cancers where it portends a poor prognosis and plays a key role in the generation of metastasis. However, the mechanisms that Chi3l1 uses to mediate these responses and the pathways that control Chi3l1 induced tumor responses are poorly understood. We characterized the mechanisms that Chi3l1 uses to foster tumor progression and the ability of the RIG-like helicase (RLH) innate immune response to control Chi3l1 elaboration and pulmonary metastasis. Here we demonstrate that RLH activation inhibits tumor induction of Chi3l1 and the expression of receptor IL-13Ralpha2 and pulmonary metastasis while restoring NK cell accumulation and activation, augmenting the expression of IFN alpha/beta, chemerin and its receptor ChemR23, p-cofilin, LIMK2 and PTEN and inhibiting BRAF and NLRX1 in a MAVS-dependent manner. These studies demonstrate that Chi3l1 is a multifaceted immune stimulator of tumor progression and metastasis whose elaboration and tissue effects are abrogated by RLH innate immune responses. PMID- 27198669 TI - E-cigarettes classified as tobacco products in the USA. PMID- 27198668 TI - Comparison of anesthetic agents on otoacoustic emissions in children: propofol vs ketamine. AB - BACKGROUND: Otoacoustic emission (OAE) tests are important evaluation tools for diagnosis of peripheral auditory pathology. Sedation or general anesthesia may be required for the performance of the OAE tests. The aim of this retrospective study was to compare the effects of anesthetic agents, propofol and ketamine, on OAEs in children. METHODS: Fifty healthy children who underwent tonsillectomy and/or adenoidectomy under general anesthesia were included in this study. Three anesthesia induction protocols were defined for this study and the anesthesiologist applied his or her own choice. Transient evoked otoacoustic emissions (TEOAEs) and distortion-product otoacoustic emissions (DPOAEs) were automatically recorded in both ears of each patient prior to anesthetic (predrug) and following the loss of consciousness 5 min later (postdrug) by an audiologist blinded to the method of anesthesia. Acceptable TEOAEs were defined as signal noise ratio (S/N) of above 3 dB SPL (decibel sound pressure level) and DPOAEs of 6 dB SPL or above. Between-group and within-group comparisons and correlations were performed for statistical analysis. RESULTS: Retrospective review of the anesthesia charts from 44 cases that completed the study showed that propofol, ketamine, and sevoflurane induction protocols were used in 21, 18, and 5 cases, respectively. Measurements of 36 ears in the propofol group and 34 ears in the ketamine group were included in the final analysis. Postdrug TEOAE and DPOAE amplitudes were significantly lower than predrug amplitudes except at 8 kHz in the ketamine group. There was no significant statistical difference in postdrug DPOAE measurements between propofol and ketamine groups but a significant difference was observed at 2 and 3 kHz of postdrug TEOAE measurements. TEOAE measurements were below 3 dB in 8 of 34 ears after ketamine and in 1 of 36 ears after propofol administration. There was a significant difference between the groups with respect to the incidence of successful measurements of TEOAEs. The DPOAE measurements were affected less by these drugs. CONCLUSION: DPOAE measurements were reduced similarly by propofol and ketamine anesthesia. Lower false outcome ratio in TEOAE measurements made propofol a better option than ketamine. PMID- 27198667 TI - Concordant Patterns of Brain Structure in Mothers with Recurrent Depression and Their Never-Depressed Daughters. AB - BACKGROUND: A growing body of research has demonstrated that having a mother with a history of major depressive disorder (MDD) is one of the strongest predictors of depression in adolescent offspring. Few studies, however, have assessed neural markers of this increased risk for depression, or examined whether risk-related anomalies in adolescents at maternal risk for depression are related to neural abnormalities in their depressed mothers. We addressed these questions by examining concordance in brain structure in two groups of participants: mothers with a history of depression and their never-depressed daughters, and never depressed mothers and their never-depressed daughters. METHOD: We scanned mothers with (remitted; RMD) and without (control; CTL) a history of recurrent episodes of depression and their never-depressed daughters, computed cortical gray matter thickness, and tested whether mothers' thickness predicted daughters' thickness. RESULTS: Both RMD mothers and their high-risk daughters exhibited focal areas of thinner cortical gray matter compared with their CTL/low-risk counterparts. Importantly, the extent of thickness anomalies in RMD mothers predicted analogous abnormalities in their daughters; this pattern was not present in CTL/low-risk dyads. CONCLUSIONS: We identified neuroanatomical risk factors that may underlie the intergenerational transmission of risk for MDD. Our findings suggest that there is concordance in brain structure in dyads that is affected by maternal depression, and that the location, direction, and extent of neural anomalies in high-risk offspring mirror those of their recurrent depressed mothers. PMID- 27198670 TI - Respiratory medicine: a call for papers. PMID- 27198672 TI - Current Information Gaps in Micronutrient Research, Programs and Policy: How Can We Fill Them? AB - Micronutrient (MN) interventions have a very positive effect on public health and have been a major focus of nutrition research and policy for over 3 decades. Most MN policies are established by the World Health Organization based on available evidence from well-designed trials. These include recommendations on iron + folic acid supplements for pregnancy, high-dose vitamin A supplementation for children <5 years, multiple MN supplementation in young children, food fortification, and universal salt iodization. However, important gaps remain in the evidence base, some periods of the life span have been paid insufficient attention, and some MN policies are incomplete or inconsistent. Examples include the pending decision about whether to recommend multiple MN supplementation in pregnancy or preconception, a lack of information about whether supplementation of lactating women improves breast milk quality and infant development, uncertainty about when and where fortification of complementary foods or supplements is beneficial to preschoolers, and whether folic acid fortification can be harmful in population groups with a high prevalence of vitamin B12 deficiency. The most effective dose of MNs has rarely been tested systematically. MN interventions alone are not very effective for improving the growth and development of young children. Newer methods for the analysis of MNs in breast milk are revealing low concentrations in many populations, so more information is needed on the effects of different interventions on milk nutrient content. We need to improve biomarkers of MN status and should measure multiple biological responses to MN interventions using modern nutritional science methods, including metabolomics, proteomics and epigenetics; these will reveal effects of MNs that are not yet fully appreciated. PMID- 27198671 TI - Reformulation of Fungizone by PEG-DSPE Micelles: Deaggregation and Detoxification of Amphotericin B. AB - PURPOSE: Fungizone(r) (AmB-SD), amphotericin B solubilized by sodium deoxycholate, contains a highly aggregated form of the antifungal agent that causes dose-limiting renal toxicity. With the aim of reducing the formulation's toxicity by co-delivering monomeric amphotericin B (AmB) and sodium supplementation, we deaggregated AmB-SD with FDA-approved excipient PEG-DSPE in 0.9% NaCl-USP. Herein, we describe a reformulated AmB-SD with PEG-DSPE micelles that results in a less toxic drug with maintained antifungal activity. METHODS: We compared the aggregation state and particle size of AmB-SD alone or combined with PEG-DSPE micelles. In vitro hemolytic activity and in vivo renal toxicity were measured to determine the toxicity of different formulations. In vitro antifungal assays were performed to determine differences in efficacy among formulations. RESULTS: PEG-DSPE micelles in saline deaggregated AmB-SD. Deaggregated AmB-SD exhibited significantly reduced in vitro and in vivo toxicity. In vitro antifungal studies showed no difference in minimum inhibitory and fungicidal concentrations of AmB-SD combined with PEG-DSPE relative to the drug alone. CONCLUSIONS: Reformulation of AmB-SD with PEG-DSPE micelles in saline facilitates co-delivery of monomeric AmB and sodium supplementation, potentially reducing the dose-limiting nephrotoxicity of AmB-SD. Ease of preparation and commercially available components lead us to acknowledge its potential for clinical use. PMID- 27198673 TI - Asymmetric division of clonal muscle stem cells coordinates muscle regeneration in vivo. AB - Skeletal muscle is an example of a tissue that deploys a self-renewing stem cell, the satellite cell, to effect regeneration. Recent in vitro studies have highlighted a role for asymmetric divisions in renewing rare "immortal" stem cells and generating a clonal population of differentiation-competent myoblasts. However, this model currently lacks in vivo validation. We define a zebrafish muscle stem cell population analogous to the mammalian satellite cell and image the entire process of muscle regeneration from injury to fiber replacement in vivo. This analysis reveals complex interactions between satellite cells and both injured and uninjured fibers and provides in vivo evidence for the asymmetric division of satellite cells driving both self-renewal and regeneration via a clonally restricted progenitor pool. PMID- 27198674 TI - Pore chemistry and size control in hybrid porous materials for acetylene capture from ethylene. AB - The trade-off between physical adsorption capacity and selectivity of porous materials is a major barrier for efficient gas separation and purification through physisorption. We report control over pore chemistry and size in metal coordination networks with hexafluorosilicate and organic linkers for the purpose of preferential binding and orderly assembly of acetylene molecules through cooperative host-guest and/or guest-guest interactions. The specific binding sites for acetylene are validated by modeling and neutron powder diffraction studies. The energies associated with these binding interactions afford high adsorption capacity (2.1 millimoles per gram at 0.025 bar) and selectivity (39.7 to 44.8) for acetylene at ambient conditions. Their efficiency for the separation of acetylene/ethylene mixtures is demonstrated by experimental breakthrough curves (0.73 millimoles per gram from a 1/99 mixture). PMID- 27198675 TI - Targeting of cancer neoantigens with donor-derived T cell receptor repertoires. AB - Accumulating evidence suggests that clinically efficacious cancer immunotherapies are driven by T cell reactivity against DNA mutation-derived neoantigens. However, among the large number of predicted neoantigens, only a minority is recognized by autologous patient T cells, and strategies to broaden neoantigen specific T cell responses are therefore attractive. We found that naive T cell repertoires of healthy blood donors provide a source of neoantigen-specific T cells, responding to 11 of 57 predicted human leukocyte antigen (HLA)-A*02:01 binding epitopes from three patients. Many of the T cell reactivities involved epitopes that in vivo were neglected by patient autologous tumor-infiltrating lymphocytes. Finally, T cells redirected with T cell receptors identified from donor-derived T cells efficiently recognized patient-derived melanoma cells harboring the relevant mutations, providing a rationale for the use of such "outsourced" immune responses in cancer immunotherapy. PMID- 27198676 TI - Glutathione S-transferase A1 - a sensitive marker of alcoholic injury on primary hepatocytes. AB - The primary hepatocytes were extracted and purified from mice through improved Seglen two-step perfusion method. Ethanol-induced injury hepatocytes model in mice was used to investigate the importance of glutathione S-transferase A1 (GSTA1) in hepatocytes injury by comparison with other indicators, such as alanine aminotransferase, aspartate aminotransferase, malondialdehyde, glutathione and superoxide dismutase. The release of GSTA1 was demonstrated to be an earlier and more sensitive indicator of hepatocytes injury than other indicators. Significant increases in GSTA1 were detected at 2 h after ethanol exposure, while other indicators were undetected at this time. A markedly difference in other indicators were observed at 6 and 8 h. The release of GSTA1 was significantly increased at a concentration of 50 mmol/L ethanol, the lowest exposure concentration than that in other indicators. In contrast, other indicators release was not statistically significant until concentrations of 75 mmol/L and 100 mmol/L ethanol. These results suggest that GSTA1 can be detected at the early stage of low concentration ethanol exposure and that GSTA1 is more sensitive and reliable marker in ethanol-induced hepatic injury. PMID- 27198677 TI - Micronucleus as biomarkers of cancer risk in anabolic androgenic steroids users. AB - The use of anabolic androgenic steroids (AAS) has grown among practitioners of recreational bodybuilding, with significant contributions of designer steroids, aiming muscle hypertrophy in healthy subjects. The abusive use of AAS in general is associated with adverse effects; one of the most worrisome is cancer development. The aim of this study was to evaluate the effectiveness of the cytokinesis block micronucleus (CBMN) test in human lymphocytes in identifying risk groups for cancer development in users of AAS. Blood was collected from 15 AAS users bodybuilders (G1), 20 non-users bodybuilders (G2) and 20 non-users sedentary (G3). MN analysis was performed on a minimum of 1000 binucleated lymphocytes. The occurrence of MN was significantly higher ( p < 0.05) in individuals of G1 compared to G2 and G3. The results indicate the sensitivity of CBMN in human lymphocytes in the identification of chromosomal damage in consequence of AAS. PMID- 27198678 TI - Comparison of cytotoxicity test models for evaluating resin-based composites. AB - OBJECTIVES: This study compared different cytotoxicity test models for evaluating resin-based composites (RBCs) and assessed the biocompatibility of standard and bulk-fill RBCs. METHODS: A standard (spectrum TPH) and a bulk-fill (smart dentin replacement (SDR)) RBC were selected. Disc-shaped specimens (7 mm diameter) of 2 and 4 mm thickness were polymerized for 20 s with a LED curing light of 700 mW/cm2 irradiance. The specimens ( n = 5) were subjected to micro-hardness testing and three cytotoxicity test models (direct contact, indirect contact and extract tests) with the established L-929 cell line. Hardness ratios of top and bottom surfaces of specimens were computed to assess the effectiveness of cure. For the direct and indirect contact tests, the cells were stained and zones of inhibition were analyzed after material contact for 24 h. For the extract test, cells were exposed to extracts for 24 h, and cell viability was measured. Data was analyzed using analysis of variance/Scheffe's post hoc test and Pearson's correlation ( p < 0.05). RESULTS: The lowest mean hardness ratio and highest cytotoxicity were observed for TPH at 4 mm. At 4-mm thickness, SDR was found to be biocompatible with all three models. Correlations between hardness ratio and cell viability ranged from r = 0.89-0.96 for the various tests. A significant correlation ( r = 0.97) was also observed between the three test models. CONCLUSION: Our data indicated consistency between direct contact, indirect contact and extract test models for cytotoxicity testing of RBCs. Bulk placement and curing at 4 mm for the bulk-fill RBC evaluated did not result in undue cytotoxicity. PMID- 27198679 TI - Bioresorbable Scaffolds for the Management of Coronary Bifurcation Lesions. AB - The use of bioresorbable scaffolds (BRS) may be associated with benefits including restoration of endothelial function, positive vessel remodeling, and reduced risk for very late (stent) thrombosis compared with metallic stents by virtue of their complete absorption within 3 to 4 years of implantation. When treating bifurcation lesions, these advantages may be even more pronounced. The aim of this review is to summarize current experiences and technical considerations of bifurcation treatment with BRS. Because of the physical properties of current-generation BRS, there are concerns with regard to the efficacy and safety of this novel technology for the treatment of bifurcations, with the potential for increased rates of scaffold thrombosis and side-branch occlusions, and as a consequence, bifurcations have been excluded from the major BRS trials. Nevertheless, BRS have been used for this indication in clinical practice, as evidenced by "real-world" registries. Considering the potential limitations, specific technical considerations and modified bifurcation strategies should be used in an attempt to attenuate problems and achieve optimal procedural and clinical outcomes. PMID- 27198680 TI - Angiographic and Clinical Outcomes After Everolimus-Eluting Stenting for Unprotected Left Main Disease and High Anatomic Coronary Complexity. AB - OBJECTIVES: This study determined angiographic and clinical outcomes after everolimus-eluting stent (EES)-supported percutaneous coronary intervention for unprotected left main disease (ULMD) and high SYNTAX (SYNergy between PCI with TAXus and Cardiac Surgery) trial score (>=33). BACKGROUND: The SYNTAX trial has shown the superiority of coronary surgery over percutaneous coronary intervention (PCI) in patients with ULMD and complex coronary anatomy. It has been hypothesized that, if newer generation drug-eluting stents had been used in the SYNTAX trial, there would have been a significant reduction in clinical events. METHODS: Patients had angiograms scored according to the SYNTAX score algorithm and were divided into 2 groups: those with SYNTAX score of >=33 and those with <33. The main endpoints were ULMD restenosis and 3-year cardiac mortality. RESULTS: From May 2008 to July 2014, 393 patients underwent EES implantation for ULMD (181 patients had a SYNTAX score >=33, whereas 212 patients had a SYNTAX score <33). Overall, the restenosis rate was 4.9% (6% in SYNTAX patients scoring >=33 and 4.1% in SYNTAX patients scoring <33; p = 0.399). On multivariate analysis, the only variable related to restenosis was stent length (odds ratio [OR]: 1.06; 95% confidence interval [CI]: 1.02 to 1.09; p = 0.002). Three-year cardiac survival rates were 99 +/- 1% and 98 +/- 2% in patients with European system for cardiac operative risk evaluation (EuroSCORE) <6 and SYNTAX <33 and >=33, respectively, and 90 +/- 3% and 87 +/- 3% in patients with a EuroSCORE >6 and SYNTAX score <33 and >=33, respectively. EuroSCORE was strongly related to cardiac mortality, while the SYNTAX score >=33 was not both in patients with a EuroSCORE <6 or >=6, and there were no interactions between EuroSCORE and SYNTAX score >=33. CONCLUSIONS: For ULMD patients, high anatomical complexity as defined by a SYNTAX score >=33 is not predictive of clinical outcome after PCI. (TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX]; NCT00114972). PMID- 27198681 TI - Navigating Optimal Revascularization for Unprotected Left Main Disease in Changing Interventional Seas. PMID- 27198682 TI - Utilizing Post-Intervention Fractional Flow Reserve to Optimize Acute Results and the Relationship to Long-Term Outcomes. AB - OBJECTIVES: This study sought to evaluate the impact of fractional flow reserve (FFR) after percutaneous coronary intervention (PCI) on subsequent in-lab interventional management vessels that had undergone pre-PCI FFR and its prognostic value in predicting long-term (>1 year) outcomes. BACKGROUND: Post-PCI FFR has been shown to be a predictor of intermediate-term (6 months) adverse events. However, its impact on immediate post procedure clinical decision making and long-term outcomes is not known. METHODS: Consecutive patients undergoing PCI who had pre- and post-PCI FFR evaluations were followed for major adverse cardiovascular events (MACE). RESULTS: In the study 574 patients (664 lesions) were followed for 31 +/- 16 months. PCI led to significant improvement in FFR from 0.65 +/- 0.14 to 0.87 +/- 0.08 (p < 0.0001). Despite satisfactory angiographic appearance, 143 lesions (21%) demonstrated post-PCI FFR in the ischemic range (FFR <=0.81). After subsequent interventions, FFR in this subgroup increased from 0.78 +/- 0.08 to 0.87 +/- 0.06 (p < 0.0001). Final FFR cutoff of <=0.86 had the best predictive accuracy for MACE and <=0.85 for TVR. Patients who achieved final FFR >0.86 had significantly lower MACE compared to the final FFR <=0.86 group (17% vs. 23%; log-rank p = 0.02). Final FFR <=0.86 had incremental prognostic value over clinical and angiographic variables for MACE prediction. CONCLUSIONS: Post-PCI FFR reclassified 20% of angiographically satisfactory lesions, which required further intervention thereby providing an opportunity for complete functional optimization at the time of the index procedure. This is particularly important as FFR post-PCI FFR was a powerful independent predictor of long-term outcomes. PMID- 27198683 TI - Why Is Fractional Flow Reserve After Percutaneous Coronary Intervention Not Always 1.0? PMID- 27198684 TI - Optimal P2Y12 Inhibitor in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: A Network Meta Analysis. AB - OBJECTIVES: The study sought to compare the clinical efficacy and safety of P2Y12 inhibitors in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous intervention (PPCI). BACKGROUND: Limited data exist regarding the comparative efficacy and safety of P2Y12 inhibitors in STEMI patients undergoing PPCI. METHODS: Clinical trials enrolling STEMI patients were identified and relevant data was extracted. Major adverse cardiovascular events (MACE) were defined as the composite of all cause mortality, MI, and target vessel revascularization. Network meta-analysis was performed using Bayesian methods. RESULTS: A total of 37 studies with 88,402 STEMI patients and 5,077 MACE were analyzed. Outcomes at 1 month (22 studies and 60,783 patients) suggest that prasugrel was associated with: lower MACE than clopidogrel (standard dose odds ratio [OR]: 0.59, 95% confidence interval [CI]: 0.50 to 0.69; high-dose OR: 0.60, 95% CI: 0.51 to 0.71; upstream OR: 0.79, 95% CI: 0.66 to 0.94), and ticagrelor (standard dose OR: 0.69, 95% CI: 0.56 to 0.84; upstream OR: 0.72, 95% CI: 0.50 to 1.05); lower mortality and MI than clopidogrel and standard ticagrelor; lower stroke risk than standard clopidogrel and standard or upstream ticagrelor; and lower stent thrombosis than standard or upstream clopidogrel. At 1-year (10 studies, n = 40,333) prasugrel was associated with lower mortality and MACE than other P2Y12 inhibitors. MACE was particularly lower with prasugrel in studies where patients received bivalirudin, drug-eluting stents, and but not glycoprotein IIb/IIIa inhibitor. CONCLUSIONS: In STEMI patients undergoing PPCI, prasugrel and ticagrelor are more efficacious than clopidogrel; in addition, prasugrel was superior to ticagrelor particularly in conjunction with bivalirudin and drug-eluting stents. PMID- 27198685 TI - Optimal P2Y12 Inhibitor for Primary Percutaneous Coronary Intervention in ST Segment Elevation Myocardial Infarction: Network Meta-Analysis in the Data-Free Zone: Do You Believe in Magic? PMID- 27198687 TI - Clinical Significance of Leaks Following Left Atrial Appendage Ligation With the LARIAT Suture Delivery Device. PMID- 27198686 TI - Clinical Implications of Leaks Following Left Atrial Appendage Ligation With the LARIAT Device. AB - OBJECTIVES: The aim of this study was to evaluate the incidence and clinical implications of leaks (acute incomplete occlusion, early and late reopenings) following LAA ligation with the LARIAT device. BACKGROUND: Percutaneous LAA ligation with the LARIAT device may represent an alternative for stroke prevention in high-risk patients with atrial fibrillation with contraindications to oral anticoagulation. METHODS: This was a retrospective, multicenter study of 98 consecutive patients undergoing successful LAA ligation with the LARIAT device. Leaks were defined as the presence of flow as evaluated by transesophageal echocardiography (TEE). TEE was performed during the procedure, at 6 and 12 months, and after thromboembolic events. RESULTS: Leaks were detected in 5 (5%), 14 (15%), and 19 (20%) patients at the 3 time points. During follow up, 5 patients developed neurological events (4 strokes and 1 transient ischemic attack). Two occurred early (1 fatal stroke and 1 stroke with multiple recurrences in the following months), and TEE was not repeated after the events. The remaining 3 occurred late (after 6 months) and were associated with small leaks (<5 mm). In 2 of 3 cases, such a small leak was missed by the standard evaluation on 2-dimensional TEE, being evident only with the aid of 3-dimensional imaging. CONCLUSIONS: Incomplete occlusion of the LAA after LARIAT ligation is relatively common and may be associated with thromboembolic events. Proper long term surveillance with careful TEE should be considered to detect leaks, which can be managed with either resumption of oral anticoagulation or percutaneous transcatheter closure. PMID- 27198688 TI - Reply: Importance of Cost-Comparison Analysis in Comparing Operative and Tanscatheter Closure of Atrial Septal Defects. PMID- 27198689 TI - Importance of Cost-Comparison Analysis in Comparing Operative and Tanscatheter Closure of Atrial Septal Defects. PMID- 27198690 TI - So We Have Bioresorbable Scaffolds: Now What? PMID- 27198691 TI - Acute Heart Failure Caused by Dislocation of a WATCHMAN Left Atrial Appendage Occluder. PMID- 27198692 TI - Helicobacter pylori promotes angiogenesis depending on Wnt/beta-catenin-mediated vascular endothelial growth factor via the cyclooxygenase-2 pathway in gastric cancer. AB - BACKGROUND: Helicobacter pylori is an important pathogenic factor in gastric carcinogenesis. Angiogenesis (i.e., the growth of new blood vessels) is closely associated with the incidence and development of gastric cancer. Our previous study found that COX-2 stimulates gastric cancer cells to induce expression of the angiogenic growth factor VEGF through an unknown mechanism. Therefore, the aim of this study was to clarify the role of angiogenesis in H. pylori-induced gastric cancer development. METHODS: To clarify the relationship between H. pylori infection and angiogenesis, we first investigated H. pylori colonization, COX-2, VEGF, beta-catenin expression, and microvessel density (MVD) in gastric cancer tissues from 106 patients. In addition, COX-2, phospho-beta-catenin, and beta-catenin expression were measured by western blotting, and VEGF expression was measured by ELISA in H. pylori-infected SGC7901 and MKN45 human gastric cancer cells. RESULTS: H. pylori colonization occurred in 36.8 % of gastric carcinoma samples. Furthermore, COX-2, beta-catenin, and VEGF expression, and MVD were significantly higher in H. pylori-positive gastric cancer tissues than in H. pylori-negative gastric cancer tissues (P < 0.01). H. pylori infection was not related to sex or age in gastric cancer patients, but correlated with the depth of tumor invasion, lymph node metastasis, and tumor-node-metastasis stage (P < 0.05) and correlated with the COX-2 expression and beta-catenin expression(P < 0.01). Further cell experiments confirmed that H. pylori infection upregulated VEGF in vitro. Further analysis revealed that H. pylori-induced VEGF expression was mediated by COX-2 via activation of the Wnt/beta-catenin pathway. CONCLUSIONS: The COX-2/Wnt/beta-catenin/VEGF pathway plays an important role in H. pylori-associated gastric cancer development. The COX-2/Wnt/beta-catenin pathway is therefore a novel therapeutic target for H. pylori-associated gastric cancers. PMID- 27198693 TI - Comparative metabolomic analysis reveals a reactive oxygen species-dominated dynamic model underlying chilling environment adaptation and tolerance in rice. AB - Cold, a major environmental stress for plants, has been studied intensively for decades. Its response system has been revealed, especially at the transcriptional level. The mechanisms underlying recovery growth and environmental adaptation, however, remain unknown. Taking advantage of a naturally existing system, two subspecies of Asian cultivated rice (Oryza sativa) with significant divergence in chilling tolerance, we analyzed representative japonica and indica varieties, Nipponbare and 93-11, using comparative metabolomic analysis at six time points covering chilling treatment and recovery. In total, 223 known metabolites were detected. During chilling treatment, significant biochemical changes were centered on antioxidation. During recovery, a wide-ranging chilling response was observed. Large-scale amino acid accumulation occurred, consistent with the appearance of chilling injury. At the mid-treatment stage, the accumulation of antioxidation-related compounds appeared earlier in Nipponbare than in 93-11, consistent with the higher reactive oxygen species (ROS) levels in japonica vs indica varieties. A significant contribution of ROS-mediated gene regulation, rather than the C-repeat binding factor/dehydration-responsive-element binding factor (CBF/DREB) regulon, to the more vigorous transcriptional stress response in Nipponbare was revealed by RNA-seq. Accordingly, during recovery, the induction of stress-tolerant-related metabolites was more active in the chilling tolerant variety Nipponbare. Senescence-related compounds accumulated only in the chilling-sensitive variety 93-11. Our study uncovers the dynamic metabolic models underlying chilling response and recovery, and reveals a ROS-dominated rice adaptation mechanism to low-temperature environments. PMID- 27198695 TI - Patient care worsens as NHS deficits persist. PMID- 27198694 TI - Reconstruction of gene regulatory networks reveals chromatin remodelers and key transcription factors in tumorigenesis. AB - BACKGROUND: Alterations in genetic and epigenetic landscapes are known to contribute to the development of different types of cancer. However, the mechanistic links between transcription factors and the epigenome which coordinate the deregulation of gene networks during cell transformation are largely unknown. METHODS: We used an isogenic model of stepwise tumorigenic transformation of human primary cells to monitor the progressive deregulation of gene networks upon immortalization and oncogene-induced transformation. We applied a systems biology approach by combining transcriptome and epigenome data for each step during transformation and integrated transcription factor-target gene associations in order to reconstruct the gene regulatory networks that are at the basis of the transformation process. RESULTS: We identified 142 transcription factors and 24 chromatin remodelers/modifiers (CRMs) which are preferentially associated with specific co-expression pathways that originate from deregulated gene programming during tumorigenesis. These transcription factors are involved in the regulation of divers processes, including cell differentiation, the immune response, and the establishment/modification of the epigenome. Unexpectedly, the analysis of chromatin state dynamics revealed patterns that distinguish groups of genes which are not only co-regulated but also functionally related. Decortication of transcription factor targets enabled us to define potential key regulators of cell transformation which are engaged in RNA metabolism and chromatin remodeling. CONCLUSIONS: We reconstructed gene regulatory networks that reveal the alterations occurring during human cellular tumorigenesis. Using these networks we predicted and validated several transcription factors as key players for the establishment of tumorigenic traits of transformed cells. Our study suggests a direct implication of CRMs in oncogene induced tumorigenesis and identifies new CRMs involved in this process. This is the first comprehensive view of the gene regulatory network that is altered during the process of stepwise human cellular tumorigenesis in a virtually isogenic system. PMID- 27198696 TI - Loss of Biventricular Pacing: When Common Problems have Unusual Remedies. PMID- 27198697 TI - Postnatal Development of the Degu (Octodon degus) Endocrine Stress Response Is Affected by Maternal Care. AB - Maternal stress and care significantly affect offspring's future behavior and physiology. Studies in laboratory rats have shown that maternal stress decreases maternal care and that low rates of certain maternal behaviors cause offspring to develop hyperreactive stress responses. Plurally breeding rodents that practice communal care, such as degus (Octodon degus), may be able to buffer some of these effects since offspring receive care from multiple females. Directly after parturition, 0% (Control group), 50% (Mixed group), or 100% (CORT group) per cage of pair-housed female degus were implanted with 21-day release cortisol pellets. The amount of maternal care provided by females was determined from video recordings during the next 3 weeks. Females with cortisol implants did not alter rates of maternal care. However, females recently introduced to captivity had low rates of pup contact and pup retrievals compared to females of captive origin. When pups reached 4 weeks of age, we determined their baseline and stress-induced cortisol levels, in addition to assessing their negative feedback efficacy and adrenal sensitivity. Pups from mothers recently introduced to captivity had weak negative feedback. Within captive pups, those from CORT mothers weighed less compared to pups from either Control or Mixed mothers. Captive CORT pups also had weak adrenal sensitivity compared to captive Control pups. These findings demonstrate that maternal care and glucocorticoid elevation impact certain components of the degu pup stress response, but that plural breeding with communal care may buffer some of these effects. PMID- 27198698 TI - Antenatal diagnosis of idiopathic dilatation of pulmonary artery with 3D power doppler imaging. AB - We present a case of antenatal diagnosis of idiopathic dilatation of the pulmonary artery by three-dimensional power Doppler imaging (HDliveFlow with silhouette mode). Two-dimensional sonography clearly demonstrated a 10.4-mm diameter fetal pulmonary artery (PA), whereas the aorta (Ao) diameter was 5.04 mm. HDliveFlow clearly demonstrated the spatial relationships and different sizes of PA and Ao. The PA size returned to normal (8.0 mm) on the 11th day after birth (Ao: 9.0 mm). HDliveFlow may be an adjunctive tool to two-dimensional sonography to diagnose abnormalities of fetal great vessels. (c) 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:121-123, 2017. PMID- 27198699 TI - Arachnophobia alleviated by subthalamic nucleus stimulation for Parkinson's disease. AB - We report on a Parkinson patient with motor fluctuations and dyskinesias in whom deep brain stimulation (DBS) of the subthalamic nucleus (STN) not only improved motor symptoms but also pre-existing arachnophobia. Arachnophobia had been unchanged by the course of Parkinson's disease but rapidly improved with STN-DBS. Both, motor effects and the improvement of arachnophobia were stable during 2 years follow-up. To our knowledge this is the first report on STN stimulation effects on a specific phobia. PMID- 27198701 TI - Leadership metaphors. AB - Purpose This paper aims to suggest that the language typically used about leadership in healthcare tells us something important about how we see it. Design/methodology/approach Three main metaphors currently adopted for healthcare leadership purposes are explored - military, sporting and finance. Findings The language used about leadership sustains the way the world is seen. A more life affirming use of language is possible, which more accurately reflects what healthcare is about. Originality/value The paper builds on the work of Gareth Morgan in applying the use of metaphors to healthcare leadership. PMID- 27198702 TI - Assessing the role of GPs in Nordic health care systems. AB - Purpose This paper examines the changing role of general practitioners (GPs) in Nordic countries of Sweden, Norway and Denmark. It aims to explore the "gate keeping" role of GPs in the face of current changes in the health care delivery systems in these countries. Design/methodology/approach Data were collected from existing literature, interviews with GPs, hospital specialists and representatives of Danish regions and Norwegian Medical Association. Findings The paper contends that in all these changes, the position of the GPs in the medical division of labor has been strengthened, and patients now have increased and broadened access to choice. Research limitations/implications Health care cost and high cancer mortality rates have forced Nordic countries of Sweden, Norway and Denmark to rethink their health care systems. Several attempts have been made to reduce health care cost through market reform and by strenghtening the position of GPs. The evidence suggests that in Norway and Denmark, right incentives are in place to achieve this goal. Sweden is not far behind. The paper has limitations of a small sample size and an exclusive focus on GPs. Practical implications Anecdotal evidence suggests that physicians are becoming extremely unhappy. Understanding the changing status of primary care physicians will yield valuable information for assessing the effectiveness of Nordic health care delivery systems. Social implications This study has wider implications of how GPs see their role as potential gatekeepers in the Nordic health care systems. The role of GPs is changing as a result of recent health care reforms. Originality/value This paper contends that in Norway and Denmark, right incentives are in place to strengthen the position of GPs. PMID- 27198700 TI - Disease-specific longevity of impulse generators in deep brain stimulation and review of the literature. AB - Deep brain stimulation (DBS) represents an established and internationally approved therapy for movement disorders. In the present retrospective analysis, we evaluated disease-specific longevity of dual channel impulse generators (IPG) used in different movement disorders. We correlated the battery lifetime with electrical stimulation settings, "total electrical energy delivered" (TEED), stimulation modi (monopolar, double monopolar and bipolar) and targets. Specifically, we reviewed the longevity and stimulation settings of 464 IPGs implanted between 1996 until 2011 in a single university center. Disease entities comprised Parkinson's disease (PD, n = 257), dystonia (n = 130) and essential tremor (ET, n = 50). Further subanalyses aimed at assessing differential longevity in different subtypes of PD and dystonia. The main finding relates to longer IPG longevity in ET (thalamic DBS) and PD (subthalamic DBS) vs. dystonia (pallidal DBS; 71.9 +/- 6.7 vs. 51.5 +/- 2.3 vs. 37 +/- 2 months). In PD the tremor-dominant type was associated with a significant shorter battery survival than in the akinetic-rigid type without tremor or the "balanced" type with tremor, bradykinesia and rigidity (38.8 +/- 3.9 vs. 53.6 +/- 3.4 vs. 58.8 +/- 4.1 months), while there were no significant differences in longevity between the subtypes of dystonia. Frequency, amplitude, pulse widths and TEED correlated inversely with battery lifetime. Pallidal DBS in dystonia is associated with a shorter lifetime of IPGs than subthalamic or thalamic DBS for PD or ET. The present results may contribute to the rapidly evolving refinement of DBS devices. Future studies that assess energy consumption both in patients with and without IPG replacement could help to avoid potential underestimation of longevity of IPGs. PMID- 27198703 TI - Leading change: introducing an electronic medical record system to a paramedic service. AB - Purpose Leaders in health-care organizations introducing electronic medical records (EMRs) face implementation challenges. The adoption of EMR by the emergency medical and ambulance setting is expected to provide wide-ranging benefits, but there is little research into the processes of adoption in this sector. The purpose of this study is to examine the introduction of EMR in a small emergency care organization and identify factors that aided adoption. Design/methodology/approach Semi-structured interviews with selected paramedics were followed up with a survey issued to all paramedics in the company. Findings The user interfaces with the EMR, and perceived ease of use, were important factors affecting adoption. Individual paramedics were found to have strong and varied preferences about how and when they integrated the EMR into their practice. As company leadership introduced flexibility of use, this enhanced both individual and collective ability to make sense of the change and removed barriers to acceptance. Research limitations/implications This is a case study of one small organization. However, there may be useful lessons for other emergency care organizations adopting EMR. Practical implications Leaders introducing EMR in similar situations may benefit from considering a sense-making perspective and responding promptly to feedback. Originality/value The study contributes to a wider understanding of issues faced by leaders who seek to implement EMRs in emergency medical services, a sector in which there has been to date very little research on this issue. PMID- 27198704 TI - Healthcare under the Panchayati Raj Institutions (PRIs) in a decentralised health system. AB - Purpose This paper aims to explore the challenges and benefits arising from the involvement of Panchayati Raj Institutions (PRIs) in the provisioning of primary healthcare in a decentralised health system of India. Design/methodology/approach A qualitative study design was used in this study. Data were collected through semi-structured interviews from 89 respondents selected from nine primary health centres across the district. A thematic analytical framework approach was used to analyse the data. Findings The research results indicate that there are several challenges resulting from PRIs involvement, including prioritisation of service providers and users, coercive unethical work and lack of communication. However, there are some benefits associated with the involvement of the PRIs in service provisioning, including improved availability and regularity of healthcare providers at the health centres. Research limitations/implications The implications of the findings suggest that the PRIs play an important role in healthcare provisioning; however, their involvement is ineffective due to their partial capabilities and approach, which creates a non-conducive environment. Practical implications Health issues are among the most important human concerns, and recognising and addressing the grassroot challenges help to locate, and overcome the challenges that hinder the smooth healthcare provisioning process. Originality/value National Rural Health Mission has recognised the PRIs as a platform to promote decentralised health planning and for achieving its goals in India. The PRIs are significantly involved in planning, monitoring and provisioning of primary healthcare services at grassroot level. This paper addresses the challenges and benefits that emerged due to their involvement. PMID- 27198705 TI - Uncovering paradoxes from physicians' experiences of patient-centered ward-round. AB - Purpose The purpose of this paper is to uncover paradoxes emerging from physicians' experiences of a patient-centered and team-based ward round, in an internal medicine department. Design/methodology/approach Abductive reasoning relates empirical material to complex responsive processes theory in a dialectical process to further understandings. Findings This paper found the response from physicians, to a patient-centered and team-based ward round, related to whether the new demands challenged or confirmed individual physician's professional identity. Two empirically divergent perspectives on enacting the role of physician during ward round emerged: We-perspective and I-perspective, based on where the physician's professional identity was centered. Physicians with more of a We-perspective experienced challenges with the new round, while physicians with more of an I-perspective experienced alignment with their professional identity and embraced the new round. When identity is challenged, anxiety is aroused, and if anxiety is not catered to, then resistance is likely to follow and changes are likely to be hampered. Practical implications For change processes affecting physicians' professional identity, it is important for managers and change leaders to acknowledge paradox and find a balance between new knowledge that needs to be learnt and who the physician is becoming in this new procedure. Originality/value This paper provides increased understanding about how physicians' professional identity is interacting with a patient-centered ward round. It adds to the knowledge about developing health care in line with recent societal requests and with sustainable physician engagement. PMID- 27198706 TI - Healthcare managers' leadership profiles in relation to perceptions of work stressors and stress. AB - Purpose The purpose of this study is to investigate the relationship between leadership profiles and differences in managers' own levels of work stress symptoms and perceptions of work stressors causing stress. Design/methodology/approach Cross-sectional data were used. Healthcare managers ( n = 188) rated three dimensions of their leadership behavior and levels of work stressors and stress. Hierarchical cluster analysis was performed to identify leadership profiles based on leadership behaviors. Differences in stress-related outcomes between profiles were assessed using one-way analysis of variance. Findings Four distinct clusters of leadership profiles were found. They discriminated in perception of work stressors and stress: the profile distinguished by the lowest mean in all behavior dimensions, exhibited a pattern with significantly more negative ratings compared to the other profiles. Practical implications This paper proposes that leadership profile is an individual factor involved in the stress process, including work stressors and stress, which may inform targeted health promoting interventions for healthcare managers. Originality/value This is the first study to investigate the relationship between leadership profiles and work stressors and stress in healthcare managers. PMID- 27198707 TI - Exploring leadership in the context of dentistry in the UK. AB - Purpose The purpose of this paper is to explore selective leadership approaches in the context of dentistry in the UK. Design/methodology/approach This is a conceptual paper utilising published sources from relevant literature about leadership theory and practice and the policy background to dentistry in the UK. Findings This paper suggests that there is merit in identifying and applying an eclectic mix of leadership theory to the case of dentistry. It offers insight into individual aspects of the leadership role for dentists and applies this to the dental context. It also contrasts these individual approaches with shared leadership and suggests this may also be relevant to dentistry. It highlights the fact that leadership will be of growing concern for dentistry in the light of recent policy changes. Research limitations/implications This paper points out that there are developmental implications depending on the particular approach taken. It argues that leadership development will become increasingly important in dentistry in the UK. Originality/value This paper addresses a topic that has so far received limited attention in the literature. PMID- 27198708 TI - Indocyanine green videoangiography-assisted prediction of flap necrosis in the rat epigastric flap using the flow(r) 800 tool. AB - BACKGROUND: The decision to re-operate on a potentially ischemic free flap remains challenging. Indocyanine green videoangiography (ICG) with the FLOW(r) 800 tool is a method which allows an immediate qualitative conclusion about the patency of an anastomosis. Is it also able to predict the outcome of potentially compromised vascular free flaps? MATERIALS AND METHODS: An epigastric flap was raised and repositioned in 79 rats. Intraoperative fluorescence angiography was performed using ICG videoangiography and the FLOW(r) 800 tool was applied. Six regions of interest were positioned systematically over the flap, changes of the ICG fluorescence were color coded with respect to time and 474 measurements were performed. The flap was clinically monitored for one week and the resulting necrotic areas were correlated with the ICG/FLOW(r) 800 results. RESULTS: Mean intensity of clinically vital areas was 83.39 +/- 50.96 arbitrary units (AU) and 37.33 +/- 15.14 AU in necrotic areas. The receiver operating characteristic curve and Youden-Index analysis revealed that the optimal cutoff for the maximal intensity of ICG after FLOW(r) 800 analysis was <= 61.733 for the prediction of flap necrosis and > 61.733 for the prediction of flap survival (P < 0.0001; 95% CI = 0.85-0.91; Youden-Index: 0.67). The maximal intensity of ICG angiography had a specificity of 96.1% and sensitivity of 71.4%. The positive predictive value was 97.46% and the corresponding negative predictive value was 61.34%. CONCLUSION: This demonstrates the potential additional value of ICG videoangiography including FLOW(r) 800 analyses in the postoperative monitoring of transplanted flaps. (c) 2016 Wiley Periodicals, Inc. Microsurgery 37:235-242, 2017. PMID- 27198710 TI - Heme Trafficking and Modifications during System I Cytochrome c Biogenesis: Insights from Heme Redox Potentials of Ccm Proteins. AB - Cytochromes c require covalent attachment of heme via two thioether bonds at conserved CXXCH motifs, a process accomplished in prokaryotes by eight integral membrane proteins (CcmABCDEFGH), termed System I. Heme is trafficked from inside the cell to outside (via CcmABCD) and chaperoned (holoCcmE) to the cytochrome c synthetase (CcmF/H). Purification of key System I pathway intermediates allowed the determination of heme redox potentials. The data support a model whereby heme is oxidized to form holoCcmE and subsequently reduced by CcmF/H for thioether formation, with Fe(2+) being required for attachment to CXXCH. Results provide insight into mechanisms for the oxidation and reduction of heme in vivo. PMID- 27198712 TI - Assessment of serum thiol/disulfide homeostasis in multiple myeloma patients by a new method. AB - OBJECTIVES: The etiology of multiple myeloma (MM) is not exactly known. This study investigated the role of thiol/disulfide homeostasis in the etiopathogenesis of MM. METHODS: Some 50 patients with MM (aged 39-84 years) and 50 sex-matched healthy volunteer controls (aged 50-91 years) participated in this study. Venous blood samples were collected, and levels of native thiols, total thiols, and disulfide were measured. RESULTS: Native and total thiol levels in the control group were determined to be higher than in the study and patient groups (P<0.001). Disulfide levels were found to be higher in the control group than in the study group and higher in newly diagnosed patients than in outpatients who were undergoing treatment (P=0.002). The ratios of thiol levels were found to be similar in both the study and control groups (P>0.05). DISCUSSION: The results of the study show that although there was a decrease in the levels of disulfide, native thiol, and total thiol, the balance of thiol/disulfide was maintained. This is the first study to research the homeostasis of dynamic thiol/disulfide from the perspective of the new method that was used. We hope that this study will encourage and facilitate further studies in this area. PMID- 27198713 TI - Highly Sensitive Homogeneous Immunoassays Based on Construction of Silver Triangular Nanoplates-Quantum Dots FRET System. AB - With growing concerns about health issues worldwide, elegant sensors with high sensitivity and specificity for virus/antigens (Ag) detection are urgent to be developed. Homogeneous immunoassays (HIA) are an important technique with the advantages of small sample volumes requirement and pretreatment-free process. HIA are becoming more favorable for the medical diagnosis and disease surveillance than heterogeneous immunoassays. An important subset of HIA relies on the effect of fluorescence resonance energy transfer (FRET) via a donor-acceptor (D-A) platform, e.g., quantum dots (QDs) donor based FRET system. Being an excellent plasmonic material, silver triangular nanoplates (STNPs) have unique advantages in displaying surface plasmon resonance in the visible to near infrared spectral region, which make them a better acceptor for pairing with QDs in a FRET-based sensing system. However, the reported STNPs generally exhibited broad size distributions, which would greatly restrict their application as HIA acceptor for high detection sensitivity and specificity purpose. In this work, uniform STNPs and red-emitting QDs are firstly applied to construct FRET nanoplatform in the advanced HIA and further be exploited for analyzing virus Ag. The uniform STNPs/QDs nanoplatform based medical sensor provides a straightforward and highly sensitive method for Ag analysis in homogeneous form. PMID- 27198711 TI - The ribosome in action: Tuning of translational efficiency and protein folding. AB - The cellular proteome is shaped by the combined activities of the gene expression and quality control machineries. While transcription plays an undoubtedly important role, in recent years also translation emerged as a key step that defines the composition and quality of the proteome and the functional activity of proteins in the cell. Among the different post-transcriptional control mechanisms, translation initiation and elongation provide multiple checkpoints that can affect translational efficiency. A multitude of specific signals in mRNAs can determine the frequency of translation initiation, choice of the open reading frame, global and local elongation velocities, and the folding of the emerging protein. In addition to specific signatures in the mRNAs, also variations in the global pools of translation components, including ribosomes, tRNAs, mRNAs, and translation factors can alter translational efficiencies. The cellular outcomes of phenomena such as mRNA codon bias are sometimes difficult to understand due to the staggering complexity of covariates that affect codon usage, translation, and protein folding. Here we summarize the experimental evidence on how the ribosome-together with the other components of the translational machinery-can alter translational efficiencies of mRNA at the initiation and elongation stages and how translation velocity affects protein folding. We seek to explain these findings in the context of mechanistic work on the ribosome. The results argue in favour of a new understanding of translation control as a hub that links mRNA homeostasis to production and quality control of proteins in the cell. PMID- 27198715 TI - Organ siderosis and hemophagocytosis during acute graft-versus-host disease. PMID- 27198716 TI - Whole exome sequencing reveals activating JAK1 and STAT3 mutations in breast implant-associated anaplastic large cell lymphoma anaplastic large cell lymphoma. PMID- 27198717 TI - Immunoglobulin heavy and light chain gene features are correlated with primary cold agglutinin disease onset and activity. PMID- 27198714 TI - RNA-Seq methods for transcriptome analysis. AB - Deep sequencing has been revolutionizing biology and medicine in recent years, providing single base-level precision for our understanding of nucleic acid sequences in high throughput fashion. Sequencing of RNA, or RNA-Seq, is now a common method to analyze gene expression and to uncover novel RNA species. Aspects of RNA biogenesis and metabolism can be interrogated with specialized methods for cDNA library preparation. In this study, we review current RNA-Seq methods for general analysis of gene expression and several specific applications, including isoform and gene fusion detection, digital gene expression profiling, targeted sequencing and single-cell analysis. In addition, we discuss approaches to examine aspects of RNA in the cell, technical challenges of existing RNA-Seq methods, and future directions. WIREs RNA 2017, 8:e1364. doi: 10.1002/wrna.1364 For further resources related to this article, please visit the WIREs website. PMID- 27198718 TI - Real-world results of ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia: data from 95 consecutive patients treated in a compassionate use program. A study from the Swedish Chronic Lymphocytic Leukemia Group. AB - Ibrutinib, a Bruton's tyrosine kinase inhibitor is approved for relapsed/refractory and del(17p)/TP53 mutated chronic lymphocytic leukemia. Discrepancies between clinical trials and routine health-care are commonly observed in oncology. Herein we report real-world results for 95 poor prognosis Swedish patients treated with ibrutinib in a compassionate use program. Ninety five consecutive patients (93 chronic lymphocytic leukemia, 2 small lymphocytic leukemia) were included in the study between May 2014 and May 2015. The median age was 69 years. 63% had del(17p)/TP53 mutation, 65% had Rai stage III/IV, 28% had lymphadenopathy >=10cm. Patients received ibrutinib 420 mg once daily until progression. At a median follow-up of 10.2 months, the overall response rate was 84% (consistent among subgroups) and 77% remained progression-free. Progression free survival and overall survival were significantly shorter in patients with del(17p)/TP53 mutation (P=0.017 and P=0.027, log-rank test); no other factor was significant in Cox proportional regression hazards model. Ibrutinib was well tolerated. Hematomas occurred in 46% of patients without any major bleeding. Seven patients had Richter's transformation. This real-world analysis on consecutive chronic lymphocytic leukemia patients from a well-defined geographical region shows the efficacy and safety of ibrutinib to be similar to that of pivotal trials. Yet, del(17p)/TP53 mutation remains a therapeutic challenge. Since not more than half of our patients would have qualified for the pivotal ibrutinib trial (RESONATE), our study emphasizes that real-world results should be carefully considered in future with regards to new agents and new indications in chronic lymphocytic leukemia. PMID- 27198720 TI - Cux2 serves as a novel lineage marker of granule cell layer neurons from the rhombic lip in mouse and chick embryos. AB - BACKGROUND: The rhombic lip (RL), a germinal zone in the developing hindbrain, gives rise to all of the excitatory neurons of the cerebellum. It is presently unclear what factors distinguish between RL progenitor pools and play a role in differentiating the multiple cell types that arise from this region. The transcription factor Cux2 has been shown to play important roles in proliferation and differentiation of distinct neuronal populations during embryogenesis, but its role in cerebellar fate restriction is unknown. RESULTS: Through expression analysis and genetic fate mapping studies we show that Cux2 is expressed in the RL of the fetal brain and is restricted to a pool of cerebellar granule cell precursors and unipolar brush cells. This restriction was remarkably specific because regardless of the timing of Cux2 reporter gene activation in the RL, only granule cell layer derivatives were labeled. However, the overexpression of Cux2 in naive hindbrain tissue was insufficient to force progenitor cells to adopt a granule cell fate. CONCLUSIONS: Our results suggest that Cux2 delineates the pool of cerebellar granule cell layer progenitors from other RL and ventricular zone derivatives, and plays a role in fate restricting, but not differentiating, this population. Developmental Dynamics 245:881-896, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27198721 TI - Experimental conical-head abutment screws on the microbial leakage through the implant-abutment interface: an in vitro analysis using target-specific DNA probes. AB - OBJECTIVES: The aim of this in vitro study was to identify and quantify up to 38 microbial species from human saliva penetrating through the implant-abutment interface in two different implant connections, external hexagon and tri-channel internal connection, both with conventional flat-head or experimental conical head abutment screws. MATERIAL AND METHODS: Forty-eight two-part implants with external hexagon (EH; n = 24) or tri-channel internal (TI; n = 24) connections were investigated. Abutments were attached to implants with conventional flat head or experimental conical-head screws. After saliva incubation, Checkerboard DNA-DNA hybridization was used to identify and quantify up to 38 bacterial colonizing the internal parts of the implants. Kruskal-Wallis test followed by Bonferroni's post-tests for multiple comparisons was used for statistical analysis. RESULTS: Twenty-four of thirty-eight species, including putative periodontal pathogens, were found colonizing the inner surfaces of both EH and TI implants. Peptostreptococcus anaerobios (P = 0.003), Prevotella melaninogenica (P < 0.0001), and Candida dubliniensis (P < 0.0001) presented significant differences between different groups. Means of total microbial count (*104 , +/ SD) for each group were recorded as follows: G1 (0.27 +/- 2.04), G2 (0 +/- 0), G3 (1.81 +/- 7.50), and G4 (0.35 +/- 1.81). CONCLUSIONS: Differences in the geometry of implant connections and abutment screws have impacted the microbial leakage through the implant-abutment interface. Implants attached with experimental conical-head abutment screws showed lower counts of microorganisms when compared with conventional flat-head screws. PMID- 27198719 TI - Different spectra of recurrent gene mutations in subsets of chronic lymphocytic leukemia harboring stereotyped B-cell receptors. AB - We report on markedly different frequencies of genetic lesions within subsets of chronic lymphocytic leukemia patients carrying mutated or unmutated stereotyped B cell receptor immunoglobulins in the largest cohort (n=565) studied for this purpose. By combining data on recurrent gene mutations (BIRC3, MYD88, NOTCH1, SF3B1 and TP53) and cytogenetic aberrations, we reveal a subset-biased acquisition of gene mutations. More specifically, the frequency of NOTCH1 mutations was found to be enriched in subsets expressing unmutated immunoglobulin genes, i.e. #1, #6, #8 and #59 (22-34%), often in association with trisomy 12, and was significantly different (P<0.001) to the frequency observed in subset #2 (4%, aggressive disease, variable somatic hypermutation status) and subset #4 (1%, indolent disease, mutated immunoglobulin genes). Interestingly, subsets harboring a high frequency of NOTCH1 mutations were found to carry few (if any) SF3B1 mutations. This starkly contrasts with subsets #2 and #3 where, despite their immunogenetic differences, SF3B1 mutations occurred in 45% and 46% of cases, respectively. In addition, mutations within TP53, whilst enriched in subset #1 (16%), were rare in subsets #2 and #8 (both 2%), despite all being clinically aggressive. All subsets were negative for MYD88 mutations, whereas BIRC3 mutations were infrequent. Collectively, this striking bias and skewed distribution of mutations and cytogenetic aberrations within specific chronic lymphocytic leukemia subsets implies that the mechanisms underlying clinical aggressiveness are not uniform, but rather support the existence of distinct genetic pathways of clonal evolution governed by a particular stereotyped B-cell receptor selecting a certain molecular lesion(s). PMID- 27198722 TI - Multifaceted impact of trichothecene metabolites on plant-microbe interactions and human health. AB - Fungi present in rhizosphere produce trichothecene metabolites which are small in size and amphipathic in nature and some of them may cross cell membranes passively. Hypocreaceae family of rhizosphere fungi produce trichothecene molecules, however it is not a mandatory characteristic of all genera. Some of these molecules are also reported as growth adjuvant, while others are reported as deleterious for the plant growth. In this review, we are exploring the roles of these compounds during plant-microbe interactions. The three-way interaction among the plants, symbiotic microbial agents (fungi and bacteria), and the pathogenic microbes (bacteria, fungi) or multicellular pathogens like nematodes involving these compounds may only help us to understand better the complex processes happening in the microcosm of rhizosphere. These metabolites may further modulate the activity of different proteins involved in the cell signalling events of defence-related response in plants. That may induce the defence system against pathogens and growth promoting gene expression in plants, while in animal cells, these molecules have reported biochemical and pharmacological effects such as inducing oxidative stress, cell-cycle arrest and apoptosis, and may be involved in maintenance of membrane integrity. The biochemistry, chemical structures and specific functional group-mediated activity of these compounds have not been studied in details yet. Few of these molecules are also recently reported as novel anti-cancer agent against human chondrosarcoma cells. PMID- 27198723 TI - beta-Glucosidase from the hyperthermophilic archaeon Thermococcus sp. is a salt tolerant enzyme that is stabilized by its reaction product glucose. AB - beta-Glucosidase (BG) is widely applied in the biofuel's industry, as part of a cellulase cocktail to catalyze the hydrolysis of the beta-1,4 linkages that join two glucose molecules in a cellulose polymer. The hydrolysis step is generally recognized as the major limiting step in the development of efficient enzyme based technologies for the conversion of lignocellulosic biomass to sugars and the production of biofuels due to the accumulation of the reaction product, glucose. Relieving this glucose inhibition of BG is therefore a major challenge. In this study, O08324, a putative BG gene encoded in the hyperthermophilic archaeon Thermococcus sp., was cloned and overexpressed in Escherichia coli. O08324 showed maximum activity between pH 5-6.8 and at 78 degrees C and was thermostable with a half-life of 860 min at 78 degrees C in the presence of 1.5 M glucose. O08324 was not inhibited by glucose up to the highest assayable concentration of 4 M and also shows no decrease in activity in the presence of up to 4 M of sodium chloride or potassium chloride. O08324 supplementation of Trichoderma viride cellulase enhanced glucose production by more than 50 % compared to a commercially available BG, when Avicel (10 %, w/v) was used as a substrate at 37 degrees C. Multiple sequence alignments across previously reported glucose-tolerant BGs shows that many conserved residues previously implicated in glucose tolerance are not conserved in this BG suggesting a need for a relook at understanding the molecular basis of glucose tolerance. PMID- 27198724 TI - Fungal biotransformation of tanshinone results in [4+2] cycloaddition with sorbicillinol: evidence for enzyme catalysis and increased antibacterial activity. AB - The biotransformation of tanshinone IIA to a new antibacterial agent tanshisorbicin (1) by the fungus Hypocrea sp. (AS 3.17108) is described. The structure of tanshisorbicin is a hybrid of tanshinone IIA (2) and sorbicillinol (3). The latter is a metabolite produced by Hypocrea sp. The structure of tanshisorbicin was determined using mass spectrometry, NMR spectroscopy, and ECD calculations. The anti-MRSA activity of 1 was found to be significantly higher than that of the parent substrate Tan IIA. Preliminary experiments indicate that tanshisorbicin is formed via a [4+2] cycloaddition reaction that is likely catalyzed by microbial enzyme. PMID- 27198725 TI - Three important amino acids control the regioselectivity of flavonoid glucosidation in glycosyltransferase-1 from Bacillus cereus. AB - Glycosyltransferase-1 from Bacillus cereus (BcGT1) catalyzes a reaction that transfers a glucosyl moiety to flavonoids, such as quercetin, kaempferol, and myricetin. The enzymatic glucosidation shows a broad substrate specificity when the reaction is catalyzed by wild-type BcGT1. Preliminary assays demonstrated that the F240A mutant significantly improves the regioselectivity of enzymatic glucosidation toward quercetin. To unveil and further to control the catalytic function of BcGT1, mutation of F240 to other amino acids, such as C, E, G, R, Y, W, and K, was performed. Among these mutants, F240A, F240G, F240R, and F240K greatly altered the regioselectivity. The quercetin-3-O-glucoside, instead of quercetin-7-O-glucoside as for the wild-type enzyme, was obtained as the major product. Among these mutants, F240R showed nearly 100 % product specificity but only retained 25 % catalytic efficiency of wild-type enzyme. From an inspection of the protein structure, we found two other amino acids, F132 and F138, together with F240, are likely to form a hydrophobic binding region, which is sufficiently spacious to accommodate substrates with varied aromatic moieties. Through the replacement of a phenylalanine by a tyrosine residue in the substrate-binding region, the mutants may be able to fix the orientation of flavonoids, presumably through the formation of a hydrogen bond between substrates and mutants. Multiple mutants-F240R_F132Y, F240R_F138Y, and F240R_F132Y_F138Y-were thus constructed for further investigation. The multiple points of mutants not only maintained the high product specificity but also significantly improved the catalytic efficiency, relative to F240R. The same product specificity was obtained when kaempferol and myricetin were used as a substrate. PMID- 27198727 TI - Improved shelf life of dried Beauveria bassiana blastospores using convective drying and active packaging processes. AB - The yeast form (blastospore) of the dimorphic insect-pathogenic fungus Beauveria bassiana can be rapidly produced using liquid fermentation methods but is generally unable to survive rapid dehydration processes or storage under non refrigerated conditions. In this study, we evaluated the influence of two convective drying methods, various modified atmosphere packaging systems, and storage temperatures on the desiccation tolerance, storage stability, and virulence of blastospores of B. bassiana ESALQ 1432. All blastospore formulations were dried to <5 % water content equivalent to aw < 0.3. The viability of B. bassiana blastospores after air drying and spray drying was greater than 80 %. Vacuum-packaged blastospores remained viable longer when stored at 4 degrees C compared with 28 degrees C with virtually no loss in viability over 9 months regardless the drying method. When both oxygen and moisture scavengers were added to sealed packages of dried blastospore formulations stored at 28 degrees C, viability was significantly prolonged for both air- and spray-dried blastospores. The addition of ascorbic acid during spray drying did not improve desiccation tolerance but enhanced cell stability (~twofold higher half-life) when stored at 28 degrees C. After storage for 4 months at 28 degrees C, air-dried blastospores produced a lower LC80 and resulted in higher mortality to whitefly nymphs (Bemisia tabaci) when compared with spray-dried blastospores. These studies identified key storage conditions (low aw and oxygen availability) that improved blastospore storage stability at 28 degrees C and will facilitate the commercial development of blastospores-based bioinsecticides. PMID- 27198726 TI - Identification of catalysis, substrate, and coenzyme binding sites and improvement catalytic efficiency of formate dehydrogenase from Candida boidinii. AB - Formate dehydrogenases (FDHs) are continually used for the cofactor regeneration in biocatalysis and biotransformation with hiring NAD(P)H-dependent oxidoreductases. Major weaknesses of most native FDHs are their low activity and operational stability in the catalytic reaction. In this work, the FDH from Candida boidinii (CboFDH) was engineered in order to gain an enzyme with high activity and better operational stability. Through comparing and analyzing its spatial structure with other FDHs, the catalysis, substrate, and coenzyme binding sites of the CboFDH were identified. To improve its performance, amino acids, which concentrated on the enzyme active site or in the conserved NAD(+) and substrate binding motif, were mutated. The mutant V120S had the highest catalytic efficiency (k cat/K m ) with COONH4 as it enhanced the catalytic velocity (k cat) and k cat/K m 3.48-fold and 1.60-fold, respectively, than that of the wild type. And, the double-mutant V120S-N187D had the highest k cat/K m with NAD(+) as it displayed an approximately 1.50-fold increase in k cat/K m . The mutants showed higher catalytic efficiency than other reported FDHs, suggesting that the mutation has achieved good results. The single and double mutants exhibited higher thermostability than the wild type. The structure-function relationship of single and double mutants was analyzed by homology models and site parsing. Asymmetric synthesis of L-tert-leucine was executed to evaluate the ability of cofactor regeneration of the mutants with about 100 % conversion rates. This work provides a helpful theoretical reference for the evolution of an enzyme in vitro and promotion of the industrial production of chiral compounds, e.g., amino acid and chiral amine. PMID- 27198729 TI - Density functional theory of nematic elasticity: softening from the polar order. AB - Recent experiments have evidenced some unconventional features in the elasticity of nematics, which cannot be explained by standard microscopic theories. Here, in the framework of a second-virial density functional theory, we have developed a general approach, relaxing the usual assumption that the angular distribution of particles with respect to their local director is unaffected by the deformation. We show that, for particles with polar symmetry, a new contribution to the splay and bend deformation free energy arises, associated with the onset of polar order. Calculations for conical and bent-shaped particles reveal dramatic softening of the splay and the bend mode, respectively, which eventually may lead to spontaneous deformation. PMID- 27198728 TI - Optimal outcomes for hearing preservation in the management of small vestibular schwannomas. AB - OBJECTIVE: To undertake a systematic review of the role of microsurgery, in relation to observation and stereotactic radiation, in the management of small vestibular schwannomas with serviceable hearing. METHODS: The Medline database was searched for publications that included the terms 'vestibular schwannoma' and/or 'acoustic neuroma', occurring in conjunction with 'hearing'. Articles were manually screened to identify those concerning vestibular schwannomas under 1.5 cm in greatest dimension. Thereafter, only publications discussing both pre operative and post-operative hearing were considered. RESULTS: Twenty-six papers were identified. Observation is an acceptable strategy for small tumours with slow growth where hearing preservation is not a consideration. In contrast, microsurgery, including the middle fossa approach, may provide excellent hearing outcomes, particularly when a small tumour has begun to cause hearing loss. Immediate post-operative hearing usually predicts long-term hearing. Recent data on stereotactic radiation suggest long-term deterioration of hearing following definitive therapy. CONCLUSION: In patients under the age of 65 years with small vestibular schwannomas, microsurgery via the middle fossa approach offers durable preservation of hearing. PMID- 27198730 TI - A metal sulfide photocatalyst composed of ubiquitous elements for solar hydrogen production. AB - A visible-light-sensitive tin sulfide photocatalyst was designed based on a ubiquitous element strategy and density functional theory (DFT) calculations. Computational analysis suggested that tin monosulfide (SnS) would be more efficient than SnS2 as a photocathode for hydrogen production because of the low ionization potential and weak ionic character of SnS. To test this experimentally, nanoparticles of SnS were loaded onto a mesoporous electrode using a wet chemical method, and the bandgap of the synthesized SnS quantum dots was found to be tunable by adjusting the number of successive ionic layer adsorption and reaction (SILAR) cycles, which controls the magnitude of the quantum confinement effect. Efficient hydrogen production was achieved when the bandgap of SnS was wider than that of the bulk form. PMID- 27198732 TI - Influence of S-Oxidation on Cytotoxic Activity of Oxathiole-Fused Chalcones. AB - Synthesis, in vitro cytotoxic activity, and interaction with tubulin of oxidized, isomeric 1-(5-alkoxybenzo[d][1,3]oxathiol-6-yl)-3-phenylprop-2-en-1-ones and 1-(6 alkoxybenzo[d][1,3]oxathiol-5-yl)-3-phenylprop-2-en-1-ones are described. Most of the compounds demonstrated cytotoxic activity at submicromolar concentrations. It was found that oxidation of sulfur atom of the oxathiole-fused chalcones strongly influenced activity of the parent compounds, and that depending on relative position of the sulfur atom in the molecule, the activity was either increased or diminished. For isomers with sulfur atom para to the chalcone carbonyl group, oxidation led to increase in activity, while for isomers with sulfur atom meta to the carbonyl the activity dropped down. It was demonstrated that the compounds interact with tubulin at the colchicine binding site, and the interaction was evaluated using molecular modeling. It was concluded that the observed profound influence of oxidation of the sulfur atom on cytotoxic activity cannot be solely related to interaction of the compounds with tubulin. PMID- 27198734 TI - Letter to the Editor regarding squamoid pattern of anaplastic thyroid carcinoma, a poorly recognized entity. PMID- 27198733 TI - Distinguishing internal property from external property in kidney transplantation. AB - What determines the ownership of human body parts? In this paper, I argue that this question can be informed by an exploration of the cognitive distinction between property external to the human body such as houses, cars or land, and internal property such as organs that are located within anatomical body confines. Each type of property has distinct brain representations and possibly different effects on the sense of self. This distinction may help explain the divergence in post-donation outcomes seen in different kidney donor populations. Poor outcomes in some types of kidney donors may be due not only to a failure in their proper selection by standard medical testing or post-donation care but may also be a manifestation of differing effects on sense of self resulting from transfer of their internal property. Because a kidney is internal property, a hypothesis worth exploring is that those who experience good outcomes post donation experience dopaminergic activation and a feeling of reward, while those experiencing bad outcomes are instead overcoming cortisol or adrenergic-based stress or fear responses without a corresponding feeling of reward, disrupting of their sense of self. Discussions about the rules for internal property transfer must be based not only on values and laws designed to govern external property but also on cognitive science-based facts, values and judgments that discussions of external property do not presently accommodate. Any future system of rules for governing organ distribution requires a framework different from that of external property to prevent harm to living kidney donors. PMID- 27198731 TI - Ageing and inflammation in patients with HIV infection. AB - Nowadays, HIV+ patients have an expected lifespan that is only slightly shorter than healthy individuals. For this reason, along with the fact that infection can be acquired at a relatively advanced age, the effects of ageing on HIV+ people have begun to be evident. Successful anti-viral treatment is, on one hand, responsible for the development of side effects related to drug toxicity; on the other hand, it is not able to inhibit the onset of several complications caused by persistent immune activation and chronic inflammation. Therefore, patients with a relatively advanced age, i.e. aged more than 50 years, can experience pathologies that affect much older citizens. HIV+ individuals with non-AIDS related complications can thus come to the attention of clinicians because of the presence of neurocognitive disorders, cardiovascular diseases, metabolic syndrome, bone abnormalities and non-HIV-associated cancers. Chronic inflammation and immune activation, observed typically in elderly people and defined as 'inflammaging', can be present in HIV+ patients who experience a type of premature ageing, which affects the quality of life significantly. This relatively new condition is extremely complex, and important factors have been identified as well as the traditional behavioural risk factors, e.g. the toxicity of anti-retroviral treatments and the above-mentioned chronic inflammation leading to a functional decline and a vulnerability to injury or pathologies. Here, we discuss the role of inflammation and immune activation on the most important non-AIDS-related complications of chronic HIV infection, and the contribution of aging per se to this scenario. PMID- 27198735 TI - Characterization of PdH-C interactions in bis-dimethyldithiocarbamate palladium(ii) and its deuterated analog by luminescence spectroscopy at variable pressure. AB - We present the variable-pressure d-d luminescence spectra of crystalline bis dimethyldithiocarbamate palladium(ii) and its deuterated analog. The energies and shifts of the band maxima provide evidence for intermolecular PdH-C interactions, with quantitative differences observed for the deuterated complex. Shifts show distinct interactions in three pressure ranges between 1 bar and 85 kbar. PMID- 27198736 TI - Reduced lysosomal acid lipase activity - A potential role in the pathogenesis of non alcoholic fatty liver disease in pediatric patients. AB - BACKGROUND: Within the spectrum of nonalcoholic fatty liver disease (NAFLD), recent evidence suggests that adult patients with nonalcoholic steatohepatitis (NASH) have significantly lower blood lysosomal acid lipase (LAL) activity than those with steatosis. This has not been studied in pediatric patients with NAFLD. AIM: Investigate blood LAL activity in pediatric patients with NAFLD and assess its correlation with histological severity. METHODS: We collected data on consecutive children with biopsy-proven NAFLD including demographics, anthropometrics, and routine laboratory tests. The histological features were graded according to the NAFLD activity scoring proposed by Kleiner et al. Blood LAL activity was measured prospectively using Lalistat 2. RESULTS: A total of 168 children were included for analysis. Mean age was 12.6+/-8.5 years, 60.1% were males and 52.4% had NASH. Children with significant fibrosis (stage 2-3, n=64) had a significantly lower LAL activity compared to those with mild fibrosis (stage 0-1, n=104). There was no significant difference in LAL activity between children with NASH compared to those without NASH. CONCLUSION: Reduced blood LAL activity correlates with severity of liver fibrosis in children with NAFLD indicating a potential role of reduced LAL activity in the pathogenesis of NAFLD induced fibrosis. PMID- 27198738 TI - Temperature-mediated phase transformation, pore geometry and pore hysteresis transformation of borohydride derived in-born porous zirconium hydroxide nanopowders. AB - Development of in-born porous nature of zirconium hydroxide nanopowders through a facile hydrogen (H2) gas-bubbles assisted borohydride synthesis route using sodium borohydride (NaBH4) and novel information on the temperature-mediated phase transformation, pore geometry as well as pore hysteresis transformation of in-born porous zirconium hydroxide nanopowders with the help of X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) isotherm and Transmission Electron Microscopy (TEM) images are the main theme of this research work. Without any surfactants or pore forming agents, the borohydride derived amorphous nature of porous powders was stable up to 500 degrees C and then the seed crystals start to develop within the loose amorphous matrix and trapping the inter-particulate voids, which led to develop the porous nature of tetragonal zirconium oxide at 600 degrees C and further sustain this porous nature as well as tetragonal phase of zirconium oxide up to 800 degrees C. The novel hydrogen (H2) gas-bubbles assisted borohydride synthesis route led to develop thermally stable porous zirconium hydroxide/oxide nanopowders with an adequate pore size, pore volume, and surface area and thus these porous materials are further suggested for promising use in different areas of applications. PMID- 27198739 TI - Numerical approach for unstructured quantum key distribution. AB - Quantum key distribution (QKD) allows for communication with security guaranteed by quantum theory. The main theoretical problem in QKD is to calculate the secret key rate for a given protocol. Analytical formulas are known for protocols with symmetries, since symmetry simplifies the analysis. However, experimental imperfections break symmetries, hence the effect of imperfections on key rates is difficult to estimate. Furthermore, it is an interesting question whether (intentionally) asymmetric protocols could outperform symmetric ones. Here we develop a robust numerical approach for calculating the key rate for arbitrary discrete-variable QKD protocols. Ultimately this will allow researchers to study 'unstructured' protocols, that is, those that lack symmetry. Our approach relies on transforming the key rate calculation to the dual optimization problem, which markedly reduces the number of parameters and hence the calculation time. We illustrate our method by investigating some unstructured protocols for which the key rate was previously unknown. PMID- 27198737 TI - Efficacy of a "contact center-based communication" in optimizing the care of inflammatory bowel diseases. AB - BACKGROUND: Telephone helplines are a useful vehicle for the management of chronic diseases even though data on how these can ease management of inflammatory bowel disease (IBD) is still scarce. AIM: to analyze our two-years' experience with the first telephone helpline dedicated to IBD in Italy. METHODS: The main outcomes of using a contact center (CC) at our Unit were analyzed; all data was prospectively collected. Patients' requests were classified into medical or non-medical. The percentage of hospitalized patients in the pre-CC period was compared to that after CC activation, to assess the potential clinical gain of using CC. The calls were divided into 5 categories to evaluate a potential correlation between patients' number of calls and risk of hospitalization. RESULTS: The CC received 11,080 calls and handled 11,972 requests. In particular, 63% of patients phoned monthly for a medical consultation, and 37% called for non medical reasons. In 2012, the followed-up patients were 1658 with 230 IBD-caused hospitalizations (14%); in 2014, the followed-up patients were 1962 with 182 hospitalizations (9%) (p<0.01). The risk of hospitalization exponentially increased with the number of calls: from 3% for 0-5 calls to 41% with >30 calls (p<0.01). CONCLUSION: A dedicated CC could provide additional clinical gain, care, and support for IBD patients. PMID- 27198740 TI - Effectual detection of group B streptococci with reduced penicillin susceptibility (PRGBS) by commercially available methicillin-resistant Staphylococcus aureus (MRSA)-selective agar. AB - We evaluated the feasibility and efficacy of a commercially available methicillin resistant Staphylococcus aureus (MRSA)-selective agar, chromID(TM) MRSA, to detect group B streptococci with reduced penicillin susceptibility (PRGBS) in this study. The results showed 72.4% (21/29) sensitivity and 98.4% (60/61) specificity to detect PRGBS using this method. PMID- 27198741 TI - Prospective multicenter surveillance identifies Staphylococcus aureus infections caused by livestock-associated strains in an agricultural state. AB - We conducted a surveillance study to investigate the epidemiology of Staphylococcus aureus infections in Iowa, using a convenience sample. Diagnostic laboratories submitted 20 S. aureus isolates per month for a 20-month period between 2011 and 2013. Of the 2226 isolates analyzed, 73.6% were methicillin resistant S. aureus (MRSA) and 26.4% were methicillin-susceptible S. aureus (MSSA). S. aureus infections in 25 patients (1%) were caused by ST398- and ST9 associated strain types, and appeared to be a common occurrence in areas of the state with the highest numbers of hogs and hog farms. Twenty nine (5.1%) of MSSA isolates and 10 (40.0%) livestock-associated strains were multi-drug resistant. PMID- 27198743 TI - Quality of care from the perspective of women with gestational diabetes in China. AB - OBJECTIVE: To explore the quality of gestational diabetes mellitus (GDM) care experienced by women in China and how it could be improved. METHODS: A qualitative study was conducted at a municipal hospital in south east China. Women who had been diagnosed with GDM at 34-38weeks of pregnancy were enrolled during two periods; between May 1 and July 31, 2012, and between April 1 and July 31, 2013. Data regarding patient-perceived care quality were collected through semi-structured individual interviews and were analyzed by qualitative content analysis. RESULTS: The study enrolled 44 patients; the interviews recorded a lack of professional care resources for GDM, a lack of high-quality personalized care for women with GDM, and patients' suggestions regarding how to improve GDM care. CONCLUSION: The participants reported a lack of high-quality GDM care, describing the core problem as an imbalance between over-stretched hospitals and low efficiency under-utilized primary healthcare centers. Clinical-practice reforms identified, particularly in primary healthcare settings, included improving services through increasing the number of health professionals and material resources to comply with diabetes guidelines, and incorporating a humanistic approach in the provision of care. PMID- 27198744 TI - Maternal 25-hydroxyvitamin D level and the occurrence of neural tube defects in Tunisia. AB - OBJECTIVE: To determine whether low vitamin D levels in pregnant women are associated with the occurrence of neural tube defects (NTDs) in Tunisia. METHODS: In a prospective study, pregnant women were recruited at a center in Tunis between January 1, 2012, and December 30, 2013. Women carrying a fetus with a severe NTD were recruited before elective termination. Matched, healthy pregnancy women were enrolled into a control group. Plasma levels of 25-hydroxyvitamin D were measured by a competitive chemiluminescence immunoassay. RESULTS: Overall, 68 women formed the NTD group and 64 the control group. The mean maternal vitamin D level was significantly lower in the NTD group (20.65+/-10.25nmol/L) than in the control group (28.30+/-13.82nmol/L; P<0.001). Vitamin D deficiency was recorded for 53 (78%) women in the NTD group and 39 (61%) in the control group. Vitamin D insufficiency was recorded for 15 (22%) women in the NTD group and 20 (31%) in the control group. Vitamin D sufficiency was found only in the control group (n=5 [8%]; P<0.001). CONCLUSION: The findings confirm an association between a decreased vitamin D level in pregnant women and the risk of fetal NTDs. PMID- 27198742 TI - Assessing the impact of common bile duct resection in the surgical management of gallbladder cancer. AB - BACKGROUND: Although radical re-resection for gallbladder cancer (GBC) has been advocated, the optimal extent of re-resection remains unknown. The current study aimed to assess the impact of common bile duct (CBD) resection on survival among patients undergoing surgery for GBC. METHODS: Patients undergoing curative-intent surgery for GBC were identified using a multi-institutional cohort of patients. Multivariable Cox-proportional hazards regression was performed to identify risk factors for a poor overall survival (OS). RESULTS: Among the 449 patients identified, 26.9% underwent a concomitant CBD resection. The median number of lymph nodes harvested did not differ based on CBD resection (CBD, 4 [IQR: 2-9] vs. no CBD, 3 [IQR: 1-7], P = 0.108). While patients who underwent a CBD resection had a worse OS, after adjusting for potential confounders, CBD resection did not impact OS (HR = 1.40, 95%CI 0.87-2.27, P = 0.170). Rather, the presence of advanced disease (T3: HR = 3.11, 95%CI 1.22-7.96, P = 0.018; T4: HR = 7.24, 95%CI 1.70-30.85, P = 0.007) and the presence of disease at the surgical margin (HR = 2.58, 95%CI 1.26-5.31, P = 0.010) were predictive of a worse OS. CONCLUSIONS: CBD resection did not yield a higher lymph node count and was not associated with an improved survival. Routine CBD excision in the re-resection of GBC is unwarranted and should only be performed selectively. J. Surg. Oncol. 2016;114:176-180. (c) 2016 Wiley Periodicals, Inc. PMID- 27198745 TI - Effect of Different Human Milk Fortifiers on Milk Composition and Growth. PMID- 27198746 TI - The Importance of Adequate Iodine during Pregnancy and Infancy. AB - Iodine requirements are increased >=50% during pregnancy. Iodine deficiency during pregnancy can cause maternal and fetal hypothyroidism and impair neurological development of the fetus. The consequences depend upon the timing and severity of the hypothyroidism; the most severe manifestation is cretinism. In iodine-deficient areas, controlled studies have demonstrated that iodine supplementation before or during early pregnancy eliminates new cases of cretinism, increases birth weight, reduces rates of perinatal and infant mortality and generally increases developmental scores in young children by 10 20%. Mild-to-moderate maternal iodine deficiency can cause thyroid dysfunction, but whether it impairs cognitive and/or neurological function in the offspring remains uncertain. In nearly all regions affected by iodine deficiency, salt iodization is the most cost-effective way of delivering iodine and improving maternal and infant health. PMID- 27198747 TI - ERRATUM. PMID- 27198748 TI - Natalizumab-treated patients at high risk for PML persistently excrete JC polyomavirus. AB - Sixty-three natalizumab-treated patients with relapsing multiple sclerosis were screened for JC polyomavirus (JCV) viruria. Urinary-positive patients were longitudinally sampled for up to 24 weeks. Using methods that distinguish encapsidated virus from naked viral DNA, 17.5 % of patients were found to excrete virus, consistent with the prevalence of urinary excretion in the general population. Unexpectedly, urinary excretion was predominantly seen (>73 %) in patients with high JC antibody index (>=2.0). Active JCV infection, therefore, tends to occur in natalizumab patients that carry a high risk factor for the development of disease, directly linking JC infection to the risk factors for PML development. PMID- 27198751 TI - Preliminaries. PMID- 27198749 TI - The Swedish SCOPA-SLEEP for assessment of sleep disorders in Parkinson's disease and healthy controls. AB - PURPOSE: SCOPA-SLEEP is a rating scale for night-time sleep and daytime sleepiness (DS) proposed for use among people with Parkinson's disease (PD) as well as others. We translated it into Swedish and assessed its psychometric properties in PD and age-matched healthy controls. METHODS: Following translation according to the dual-panel approach, the Swedish SCOPA-SLEEP was field-tested regarding comprehensibility, relevance and respondent burden (n = 20). It was then psychometrically tested according to classical test theory (data completeness, scaling assumptions, targeting, reliability and construct validity) using data from 149 people with PD and 53 age-matched healthy controls from the prospective Swedish BioFINDER study. RESULTS: SCOPA-SLEEP took a mean of 3.5 min to complete and was considered easy to use and relevant. Missing item responses were <8 %, corrected item-total correlations were >=0.47 (except for one DS item among controls), factor analyses suggested one dimension per scale, floor/ceiling effects were <=17 %, reliability was >=0.85 except for the DS scale among controls (0.65) and construct validity was supported. CONCLUSIONS: Observations concur with previous evaluations, thus providing initial support for the Swedish SCOPA-SLEEP among people with PD. Further studies are needed to establish its generic properties and to understand its measurement properties in better detail. PMID- 27198752 TI - Social simulation theory: a framework to explain nurses' understanding of patients' experiences of ill-health. AB - A fundamental aim in caring practice is to understand patients' experiences of ill-health. These experiences have a qualitative content and cannot, unlike thoughts and beliefs with conceptual content, directly be expressed in words. Nurses therefore face a variety of interpretive challenges when they aim to understand patients' subjective perspectives on disease and illness. The article argues that theories on social simulation can shed light on how nurses manage to meet these challenges. The core assumption of social simulationism is that we do not understand other people by forming mental representations of how they think, but by putting ourselves in their situation in a more imaginative way. According to simulationism, any attempt to understand a patient's behavior is made on the basis of simulating what it is like to be that patient in the given context. The article argues that this approach to social interpretation can clarify how nurses manage to achieve aims of patient understanding, even when they have limited time to communicate and incomplete knowledge of patients' perspectives. Furthermore, simulation theory provides a normative framework for interpretation, in the sense that its theoretical assumptions constitute ideals for how nurses should seek to understand patients' experiences of illness. PMID- 27198750 TI - Effects of Polybrominated Diphenyl Ethers on Rat and Human 11beta-Hydroxysteroid Dehydrogenase 1 and 2 Activities. AB - Polybrominated diphenyl ethers (PBDEs) are a class of brominated flame retardants. PBDEs have been widely used in textiles, flexible polyurethane foams, electronic components, electrical components, and plastics. 11beta-Hydroxysteroid dehydrogenases, isoform 1 (HSD11B1) and isoform 2 (HSD11B2), have been demonstrated to be the regulators of local glucocorticoid levels. In this study, the potencies of 4 different PBDEs (BDE-3, BDE-47, BDE-100, and BDE-153) with 1-6 bromine atoms attached in inhibition of rat and human HSD11B1 and HSD11B2 activities were compared to 4-bromobiphenyl (BBP), a structurally similar compound. All 4 PBDEs and BBP did not inhibit rat and human HSD11B1. BDE-3 and BDE-47 potently inhibited rat HSD11B2, and BDE-47 and BDE-153 potently inhibited human HSD11B2, with the half maximal inhibitory concentration values of 12.42, 5.95, 11.97, and 4.41 umol/l, respectively. All PBDEs noncompetitively inhibited HSD11B2 when a steroid substrate was used. However, PBDEs exerted uncompetitive inhibition when the cofactor NAD+ was used. In conclusion, some PBDEs are selective inhibitors of HSD11B2, possibly causing excessive glucocorticoid action in local tissues. PMID- 27198754 TI - Functional Outcomes of Patients Treated with Intensive Medications for Bowel and Pain Control for Low-Lying Rectal Cancer Who Received Preoperative Chemoradiotherapy. AB - PURPOSE: The aim of this study was to assess the functional outcomes of patients treated with intensive medications for bowel and pain control for low-lying rectal cancer who received preoperative chemoradiotherapy (CRT). METHODS: The inclusion criterion was sphincter-preserving surgery following CRT for T3 middle and low rectal cancer. Postoperative defecation control was conducted using calcium polycarbophil and loperamide, and anal pain control was conducted using oxycodone hydrochloride hydrate. The functional outcomes were determined by an annual questionnaire after stoma closure. RESULTS: Of 64 patients evaluated, 33 were reconstructed using the double stapling technique (DST) and 31 were reconstructed using the intersphincteric resection (ISR) technique. The median Visual Analogue Scale at ISR was improved from 7 to 1.5 at 1 year after surgery. The median Wexner scores were 6.0, 6.0, 5.0 and 5.0 for DST and 14.5, 12.0, 10.0 and 8.0 for ISR for the first 4 years, respectively. The only independent predictor of a poor bowel function (Wexner score >10) according to a multivariate analyses was pelvic infection (OR 3.994, 95% CI 1.235-13.52, p = 0.021), while ISR was not a predictor. CONCLUSIONS: Anal pain following ISR can be controlled with oxycodone hydrochloride hydrate therapy. ISR is feasible following CRT for low-lying rectal cancer. PMID- 27198756 TI - Editorial. PMID- 27198755 TI - What Is the Value of Three-Parent IVF? AB - In February 2016, the Institute of Medicine released a report, commissioned by the United States Food and Drug Administration, on the ethical and social-policy implications of so-called three-parent in vitro fertilization. The IOM endorses commencement of clinical trials on three-parent IVF, subject to some initial limitations. Also called mitochondrial replacement or transfer, three-parent IVF is an intervention comprising two distinct procedures in which the genetic materials of three people-the DNA of the father and mother and the mitochondrial DNA of an egg donor-can be used to create a child. Three-parent IVF would enable a woman with mitochondrial disease to have a genetically related child without transmitting the disease to the child. The possibility for three-parent children has prompted criticism from many corners. Critics have pointed to ethical issues including safety concerns and risks to children, genetic and germline engineering concerns, the potential exploitation of the third-parent egg donor, donor anonymity and privacy, and objections to creating babies with three parents, which undermines natural and traditional conceptions of procreation. Additionally, developing the technology would involve experimenting on, manipulating, and disposing of embryos. Although the IOM report considers the ethical concerns about the value of the three-parent IVF technology, the IOM failed to give due attention to an important objection to the development of this technology: three-parent IVF lacks the social value necessary to make investment of public resources in it ethical. Unlike the other concerns, this objection is not based on conservativism about new reproductive technologies or default favoritism of the status quo. I argue that the technology does not meet a plausible social value standard to render public research investment into its development ethical. Proponents of three-parent IVF make inaccurate and exaggerated claims that it will eradicate mitochondrial disease and save lives. Were these claims true, proponents would have a strong case for the social value of the technology. But three-parent IVF alone will not eradicate mitochondrial disease, and it will not save lives. Rather, it can create healthy lives. As I discuss, the moral distinction is crucial. Most importantly, investment in three parent IVF comes at the opportunity cost of researching treatment for mitochondrial disease that would benefit actual, living disease sufferers. PMID- 27198753 TI - The medication reconciliation process and classification of discrepancies: a systematic review. AB - AIMS: Medication reconciliation is a part of the medication management process and facilitates improved patient safety during care transitions. The aims of the study were to evaluate how medication reconciliation has been conducted and how medication discrepancies have been classified. METHODS: We searched MEDLINE, EMBASE, CINAHL, PubMed, International Pharmaceutical Abstracts (IPA), and Web of Science (WOS), in accordance with the PRISMA statement up to April 2016. Studies were eligible for inclusion if they evaluated the types of medication discrepancy found through the medication reconciliation process and contained a classification system for discrepancies. Data were extracted by one author based on a predefined table, and 10% of included studies were verified by two authors. RESULTS: Ninety-five studies met the inclusion criteria. Approximately one-third of included studies (n = 35, 36.8%) utilized a 'gold' standard medication list. The majority of studies (n = 57, 60%) used an empirical classification system and the number of classification terms ranged from 2 to 50 terms. Whilst we identified three taxonomies, only eight studies utilized these tools to categorize discrepancies, and 11.6% of included studies used different patient safety related terms rather than discrepancy to describe the disagreement between the medication lists. CONCLUSIONS: We suggest that clear and consistent information on prevalence, types, causes and contributory factors of medication discrepancy are required to develop suitable strategies to reduce the risk of adverse consequences on patient safety. Therefore, to obtain that information, we need a well-designed taxonomy to be able to accurately measure, report and classify medication discrepancies in clinical practice. PMID- 27198757 TI - [Efficacy of sodium hydroxide at 2.5 %, chlorhexidine gluconate at 0.5 % and calcium hydroxide against Candida albicans]. AB - INTRODUCTION: Endodontic flora is dominated in the apical part of the channels by strict anaerobic and some facultative anaerobic bacteria but also by Candida yeasts, especially Candida albicans species that are involved in the maintenance and persistence of endodontic infections. Their elimination of the canal system in practice by chemo-mechanical methods of disinfection is not always guaranteed. Thus, this in vitro study was performed to determine the sensitivity of C. albicans with sodium hypochlorite (NaOCl) dosed at 2.5 %, the chlorhexidine digluconate 0.5 % and calcium hydroxide used in inter-session medication. METHODS: The diffusion method was used initially to test the sensitivity of C. albicans strains with the above products. Then a dilution technique has allowed us to determine the minimum inhibitory concentration of these active products on C. albicans. RESULTS: Strains from infected pulp teeth of patients showed a sensitivity of C. albicans to sodium hypochlorite to a minimum inhibitory concentration less than 70MUg/mL and 30MUg/mL for chlorhexidine. CONCLUSION: This study demonstrated a sensitivity of C. albicans to sodium hypochlorite and chlorhexidine. PMID- 27198758 TI - Dynamic postural stability and muscle strength in patellofemoral pain: Is there a correlation? AB - BACKGROUND: Although females with patellofemoral pain (PFP) show a decrease in hip and knee muscle strength, there is a lack of studies that associates this with postural stability. The purpose of this study was to assess the dynamic postural stability and muscle strength in the hips and knees of females with and without PFP, and to verify the association between the postural stability and the muscle strength in the PFP group. METHODS: Two groups were tested: one with 25 PFP and one with 25 asymptomatic. Postural stability was evaluated during stepping up down tasks using a force platform to determine the center of pressure (COP) excursion and velocity. A handheld dynamometer was used to assess the muscles strength. The correlation analysis was conducted between the COP variables and the muscle strength. RESULTS: The PFP group demonstrated greater total and medial-lateral COP displacement (8887.7+/-761.7 vs. 8129.4+/-691.9mm, P<0.001; 32.3+/-5.5 vs. 21.7+/-2.7mm, P<0.001) and a higher total of medial lateral COP velocity (22.2+/-5.2 vs. 17.0+/-1.6 P=0.001). The PFP group showed weaknesses in all muscles (P<0.05), and there was a good positive correlation between the anterior-posterior displacement and the velocity of the extensor hip muscle (r=0.52, P<0.01; r=0.55, P<0.001). CONCLUSIONS: Subjects with PFP have frontal dynamic postural stability deficit and show an association between hip extensor and sagittal plane stability. PMID- 27198759 TI - The difference in clinical outcome of single-bundle anterior cruciate ligament reconstructions with and without remnant preservation: A meta-analysis. AB - BACKGROUND: The aim of this study was to compare the clinical performance and complications between an ACL reconstruction with a remnant-preserving single bundle technique and a standard single-bundle technique. METHODS: A search was performed of RCTs comparing the clinical outcomes and complications of ACL reconstruction with remnant-preserving and standard single-bundle techniques during October 2014. Relevant data were extracted and CONSORT was used to assess the methodological quality. Stata/SE 12.0 was used to perform a meta-analysis of the clinical outcomes. RESULTS: Six RCTs were included, with a total of 378 patients: 190 in the remnant-preservation technique group and 188 patients in standard-technique group. Assessing anterior stability, no difference was found between the groups for the KT arthrometer, negative rate of Lachman, and the pivot shift test. Assessing functional outcome, there was no significant difference in IKCD scores and grades or Lysholm score. In terms of complications, the percentage of tibial tunnel enlargement in the group of the remnant preservation technique was significantly lower, despite no significant difference in the incidence of cyclops lesions. CONCLUSIONS: The outcome of single-bundle ACL reconstruction with the remnant-preservation technique is similar to that with the standard technique in terms of anterior stability and functional recovery of the knee. Remnant preservation in ACL reconstruction decreases the percentage of tibial tunnel enlargement. Level of evidence is II. PMID- 27198760 TI - The importance of early diagnosis in spontaneous osteonecrosis of the knee - A case series with six year follow-up. AB - BACKGROUND: Spontaneous osteonecrosis of the knee has an unknown aetiology. Management options include conservative, surgical and pharmacological interventions. The aim of this study was to report the experience of the authors in conservative management of SONK using non-operative measures by analysing the functional outcome and need for surgical intervention. MATERIALS AND METHODS: All patients treated for SONK between 1st August 2001 and 1st April 2014 were retrospectively reviewed. Treatment consisted of touch-down weight bearing for around six weeks. MR imaging was evaluated for size of lesion, the condyles involved and the time taken for resolution. Tegner Activity Scale, VAS pain, Lysholm, WOMAC and IKDC scores were recorded at presentation and final follow-up (mean six years, range six months to 13years). RESULTS: Forty cases were included; the mean age of the group was 55.3years and 67.5% were male. The medial femoral condyle was the most commonly affected (52.5%). A statistically significant improvement was reported in all functional outcome measures (p<0.001). Only one patient required arthroscopic surgical intervention and no patients required arthroplasty during the follow-up period. CONCLUSION: Early stage spontaneous osteonecrosis of the knee can be managed successfully without surgery if diagnosed early. Thus early investigation of acute knee pain with MRI scanning is recommended. PMID- 27198762 TI - Tailoring nanoarchitectonics to control the release profile of payloads. AB - We demonstrate here that the control over the release rate of payloads and on the selectivity of the release can be achieved by designing nanomaterials with a hierarchical structure. Redox-responsive silica nanocapsules are first synthesized to allow for an accelerated release of the corrosion inhibitor 2 mercaptobenzothiazole as a payload upon chemical reduction and retarded release upon oxidation. In a second step, we embedded the nanocapsules into nanofibers by colloid-electrospinning, yielding a hierarchical composite structure. Remarkably, the encapsulation of the nanocapsules in the fibers provides two decisive advantages that are a higher selectivity of the release and a higher control over the release rate of payloads. PMID- 27198761 TI - Comparative study of magnetic resonance imaging (MRI) parameters in a Southeast Asian population with symptomatic patellofemoral instability. AB - BACKGROUND: MRI is performed for evaluation of soft tissue injuries associated with patellar instability. METHODS: Retrospective review of MRI parameters from a study group of 64 patients with symptomatic patellofemoral instability and a control group of 64 patients with acute knee injury without concomitant patellofemoral instability was performed. RESULTS: The study group demonstrated statistically significant increase (P<0.05) in all the MRI measurements compared to the control group. There were good inter-observer correlations between surgeon and radiologist for all radiological measurements. CONCLUSIONS: It is prudent to exercise caution in interpreting radiological parameters in different ethnic groups bearing as current treatment protocols are not ethnic-group specific. PMID- 27198763 TI - Interdependency of the maximum range of flexion-extension of hand metacarpophalangeal joints. AB - Mobility of the fingers metacarpophalangeal (MCP) joints depends on the posture of the adjacent ones. Current Biomechanical hand models consider fixed ranges of movement at joints, regardless of the posture, thus allowing for non-realistic postures, generating wrong results in reach studies and forward dynamic analyses. This study provides data for more realistic hand models. The maximum voluntary extension (MVE) and flexion (MVF) of different combinations of MCP joints were measured covering their range of motion. Dependency of the MVF and MVE on the posture of the adjacent MCP joints was confirmed and mathematical models obtained through regression analyses (RMSE 7.7 degrees ). PMID- 27198764 TI - [Social suffering: How to look at health; it is not trivial]. PMID- 27198765 TI - Distinctive proteomic profiles among different regions of human carotid plaques in men and women. AB - The heterogeneity of atherosclerotic tissue has limited comprehension in proteomic and metabolomic analyses. To elucidate the functional implications, and differences between genders, of atherosclerotic lesion formation we investigated protein profiles from different regions of human carotid atherosclerotic arteries; internal control, fatty streak, plaque shoulder, plaque centre, and fibrous cap. Proteomic analysis was performed using 2-DE with MALDI-TOF, with validation using nLC-MS/MS. Protein mapping of 2-DE identified 52 unique proteins, including 15 previously unmapped proteins, of which 41 proteins were confirmed by nLC-MS/MS analysis. Expression levels of 18 proteins were significantly altered in plaque regions compared to the internal control region. Nine proteins showed site-specific alterations, irrespective of gender, with clear associations to extracellular matrix remodelling. Five proteins display gender-specific alterations with 2-DE, with two alterations validated by nLC MS/MS. Gender differences in ferritin light chain and transthyretin were validated using both techniques. Validation of immunohistochemistry confirmed significantly higher levels of ferritin in plaques from male patients. Proteomic analysis of different plaque regions has reduced the effects of plaque heterogeneity, and significant differences in protein expression are determined in specific regions and between genders. These proteomes have functional implications in plaque progression and are of importance in understanding gender differences in atherosclerosis. PMID- 27198766 TI - Methanogenic paraffin degradation proceeds via alkane addition to fumarate by 'Smithella' spp. mediated by a syntrophic coupling with hydrogenotrophic methanogens. AB - Anaerobic microbial biodegradation of recalcitrant, water-insoluble substrates, such as paraffins, presents unique metabolic challenges. To elucidate this process, a methanogenic consortium capable of mineralizing long-chain n-paraffins (C28 -C50 ) was enriched from San Diego Bay sediment. Analysis of 16S rRNA genes indicated the dominance of Syntrophobacterales (43%) and Methanomicrobiales (26%). Metagenomic sequencing allowed draft genome assembly of dominant uncultivated community members belonging to the bacterial genus Smithella and the archaeal genera Methanoculleus and Methanosaeta. Five contigs encoding homologs of the catalytic subunit of alkylsuccinate synthase (assA) were detected. Additionally, mRNA transcripts for these genes, including a homolog binned within the 'Smithella' sp. SDB genome scaffold, were detected via RT-PCR, implying that paraffins are activated via 'fumarate addition'. Metabolic reconstruction and comparison with genome scaffolds of uncultivated n-alkane degrading 'Smithella' spp. are consistent with the hypothesis that syntrophically growing 'Smithella' spp. may achieve reverse electron transfer by coupling the reoxidation of ETFred to a membrane-bound FeS oxidoreductase functioning as an ETF:menaquinone oxidoreductase. Subsequent electron transfer could proceed via a periplasmic formate dehydrogenase and/or hydrogenase, allowing energetic coupling to hydrogenotrophic methanogens such as Methanoculleus. Ultimately, these data provide fundamental insight into the energy conservation mechanisms that dictate interspecies interactions salient to methanogenic alkane mineralization. PMID- 27198768 TI - Knockdown of phosphoethanolamine transmethylation enzymes decreases viability of Haemonchus contortus. AB - The phosphobase methylation pathway, in which phosphoethanolamine N methyltransferases (PMTs) successively catalyze the methylation of phosphoethanolamine to phosphocholine, is essential in the free-living nematode Caenorhabditis elegans. Two PMT-encoding genes (HcPMT1 and HcPMT2) cloned from Haemonchus contortus have been shown, by in vitro assays, to possess enzymatic characteristics similar to those of C. elegans PMTs, but their physiological significance in H. contortus is yet to be elucidated. Therefore, in this study, we endeavored to determine the importance of HcPMT1 and HcPMT2 in the survival of H. contortus by adapting the use of phosphorodiamidate morpholino oligomers (PPMO) antisense approach to block the translation of HcPMT1 and HcPMT2 in the worms. We found that PPMOs targeting HcPMT1 and HcPMT2 down-regulated the expression of HcPMT1 and HcPMT2 proteins in adult H. contortus. Analysis of the effect of HcPMT1 and HcPMT2 knockdown showed that it significantly decreased worm motility and viability, thus validating HcPMT1 and HcPMT2 as essential enzymes for survival of H. contortus. Studies of gene function in H. contortus have been constrained by limited forward and reverse genetic technologies for use in H. contortus. Thus, our success in adaptation of use of PPMO antisense approach in H. contortus provides an important reverse genetic technological advance for studying this parasitic nematode of veterinary significance. PMID- 27198769 TI - The role of wild ruminants as reservoirs of Besnoitia besnoiti infection in cattle. AB - Bovine besnoitiosis, a parasitic disease caused by Besnoitia besnoiti, has been reported mainly in beef cattle raised under extensive pastoral systems and is considered to be re-emerging in Western Europe. Horizontal transmission probably occurs either by means of blood sucking arthropods or as a consequence of direct contact between infected and non-infected cattle. However, the role that wild ruminants (e.g., red deer (Cervus elaphus) and roe deer (Capreolus capreolus)) may play in the parasite life cycle as putative reservoirs remains elusive. Thus, we investigated the presence of Besnoitia spp. infection in 2608 wild ruminants located in areas where bovine besnoitiosis is present and identified the Besnoitia species detected. First, a serosurvey was conducted in red deer (n=309), roe deer (n=417), Pyrenean chamois (Rupicapra p. pyrenaica, n=383) and Iberian wild goat (Capra pyrenaica hispanica, n=288) from two areas of Aragon, northeastern Spain, where bovine besnoitiosis is endemic. Second, red deer (n=820), roe deer (n=37), fallow deer (Dama dama, n=166), Iberian wild goat (n=86) and European mouflon (Ovis orientalis musimon, n=102) from southwestern Spain, where new outbreaks have recently been reported, were also sampled. The presence of Besnoitia spp.-specific antibodies was confirmed by western blot in one red deer and one roe deer from the Pyrenees, and Besnoitia spp. DNA was detected by ITS1-PCR in the seropositive red deer. Besnoitia genotyping based on 6 microsatellite (MS) analyses was carried out in red deer samples and compared with B. besnoiti genotypes from 7 in vitro isolates and 3 infected bovines, B. tarandi (1 isolate) and B. bennetti (from tissues of an infected donkey) for Besnoitia spp. assignation. Multilocus MS analysis of B. besnoiti, B. tarandi and B. bennetti showed specific genotypes for each species. A restricted genetic diversity with two genotypes by variation in a unique MS marker was revealed among the 7 B. besnoiti isolates. Incomplete Besnoitia spp. genotype of 3 MS markers from red deer samples entirely matched the B. besnoiti genotypes. Accordingly, this work gives clues for the presence of B. besnoiti infection in red deer from Western Europe. Further molecular genotyping is needed to confirm that red deer may act as an intermediate host of B. besnoiti, although the low prevalences that were found indicate that wild ruminant species do not pose a significant risk of transmitting the infection to cattle. PMID- 27198767 TI - Pretreatment neutrophil-to-lymphocyte ratio is correlated with response to neoadjuvant chemotherapy as an independent prognostic indicator in breast cancer patients: a retrospective study. AB - BACKGROUND: A high neutrophil-to-lymphocyte ratio (NLR) may be related to increased mortality in patients with lung, colorectal, stomach, liver, and pancreatic cancer. To date, the utility of NLR to predict the response to neoadjuvant chemotherapy (NAC) has not been studied. The aim of our study was to determine whether the NLR is a predictor of response to NAC and to investigate the prognostic impact of the NLR on relapse-free survival (RFS) and breast cancer specific survival (BCSS) in patients with breast cancer who received NAC. METHODS: We retrospectively studied patients who received NAC and subsequent surgical therapy for stage II-III invasive breast carcinoma at Sun Yat-sen Memorial Hospital between 2001 and 2010. The correlation of NLR with the pathological complete response (pCR) rate of invasive breast cancer to NAC was analyzed. Survival analysis was used to evaluate the predictive value of NLR. RESULTS: A total of 215 patients were eligible for analysis. The pCR rate in patients with lower pretreatment NLR (NLR < 2.06) was higher than those with higher NLR (NLR >= 2.06) (24.5 % vs.14.3 %, p < 0.05). Those patients with higher pretreatment NLR (NLR >= 2.1) had more advanced stages of cancer and higher disease-specific mortality. Through a multivariate analysis including all known predictive clinicopathologic factors, NLR >= 2.1 was a significant independent parameter affecting RFS (HR: 1.57, 95 % CI: 1.05-3.57, p < 0.05) and BCSS (HR: 2.21, 95 % CI: 1.01-4.39, p < 0.05). Patients with higher NLR (NLR >= 2.1) before treatment showed significantly lower relapse-free survival rate and breast cancer specific survival rate than those with lower NLR (NLR <2.1) (log-rank p = 0.0242 and 0.186, respectively). CONCLUSIONS: Pretreatment NLR < 2.06 is associated with pCR rate, suggesting that NLR may be an important factor predicting the response to NAC in breast cancer patients. NLR is an independent predictor of RFS and BCSS in breast cancer patients with NLR >= 2.1 who receive NAC. We suggest prospective studies to evaluate NLR as a simple prognostic test for breast cancer. PMID- 27198770 TI - Primary characterization of a putative novel TBC1 domain family member 13 from Haemaphysalis qinghaiensis. AB - A putative novel TBC1 domain family member 13 (HqTBC1D13) from Haemaphysalis qinghaiensis was cloned using rapid amplification of the cDNA ends (RACE), the HqTBC1D13 cDNA is 1702bp in length and encodes 396 amino acid residues with predicted molecular weight of 46.09kDa. The TBC-domain containing protein has a catalytic 'arginine finger' analogous to those of Ras and Rho family GAPs, which is critical determinants of GAP activity. The amino acid sequences of TBC domain were evolutionarily highly conserved across species. The partial coding sequence of HqTBC1D13 with the predicted molecular weight of 37.2kDa was expressed and purified in the PGEX-4T-1 vector. Real-time RT PCR analysis showed that the HqTBC1D13 was extensively expressed in the tested organs (salivary glands, midguts, ovaries and cuticles), and its transcriptional levels in salivary glands were significantly up-regulate induced by blood-feeding. The recombinant HqTBC1D13 protein vaccination in the rabbit model resulted in the extension of the duration of feeding and the reduction of 37% female engorgement and 14.8% oviposition compared to the control group. These results indicated that the HqTBC1D13 in ticks could be invovled in the regulation of feeding and oviposition. PMID- 27198771 TI - Hair parasite load as a new biomarker for monitoring treatment response in canine leishmaniasis. AB - Canine leishmaniasis treatment focuses on the reduction of parasite load, the clinical improvement of the animal, and the avoidance of relapses, in a scenario where the definitive parasite clearance is not achievable. Therefore, monitoring is crucial during the treatment of this disease. Quantitative PCR has been shown as an ideal tool for the treatment monitoring when quantifying parasite load in target organs such as lymph node or bone marrow, tissues that are too invasive for regular evaluation. This study aims to prove the potential of hair parasite load in the treatment monitoring of canine leishmaniasis. Six dogs were treated with meglumine antimoniate and monitored up to four months after the end of the treatment. Parasite loads in bone marrow, blood, lymph node and hair were quantified by real-time quantitative PCR. Total IgG, IgG1, and IgG2 antibody titres were analysed by immunofluorescent assay and a clinical assessment was carried out. Treatment consisted of two 28-day courses of meglumine antimoniate (100mg/kg/day) separated by an one-month interval. Analyses were performed before (day 0), during (day 60) and after treatment (day 120), and at the end of a follow-up period (day 210, four months after the end of treatment). Hair parasite load turned out to be strongly correlated with bone marrow, lymph node and blood parasite loads and with the clinical score and the IgG1 antibody titre. The evolution of this biomarker reflects the evolution of the parasitological, immunological and clinical state of the dog, highlighting its potential as a non invasive marker for the treatment monitoring in canine leishmaniasis. PMID- 27198772 TI - Efficacy and productive performance of moxidectin in feedlot calves infected with nematodes resistant to ivermectin. AB - Anthelmintic resistance (AR) of gastrointestinal nematodes to macrocyclic lactones is an increasingly common worldwide phenomenon limiting cattle production. This has motivated the search for alternatives, such as new active compounds, added drug synergisms, different doses, and alternate administration routes. The aim of this study was the assessment of moxidectin (MXD) performance in feedlot calves with a history of AR to ivermectin (IVM). Crossbred female calves aged 6-7 months and weighing 163kg (SD=34kg) were divided into 3 groups of 35 animals each. They were assigned to the following antiparasitic treatment groups: IVM group (0.2mg/kg IVM); MXD group (0.2mg/kg MXD), and ricobendazole+levamisole (RBZ+LEV) group (7.5mg/kg RBZ+8mg/kg LEV). On days 0, 26, and 47, fecal samples were taken and the weight of each animal was registered. Anthelmintic efficacy (by fecal egg count reduction), total weight gain (TWG) and average daily weight gain (AWG) were compared between the groups. A mixed SAS procedure was used for statistical analysis. Fecal egg count reduction 26 days post-treatment (PT) was calculated at 28% for the IVM group, 85% for the MXD group, and 99% for the RBZ+LEV group. AWGs (Standard Error) of 1.095g (56), 1.264g (49), and 1.340g (52) were registered for the IVM, MXD, and RBZ+LEV groups, respectively (p<0.05). Coprocultures revealed that MXD more effectively reduced Haemonchus spp. and Cooperia spp. egg counts than IVM. This resulted in higher AWGs and TWGs for this group; similar results were seen for the RBZ+LEV group as well. In this study, animals treated with MXD gained about 160 more g/day than animals treated with IVM. This represents a gain of 16 USD per animal over the 47 day trial. PMID- 27198773 TI - Profiling circulating miRNAs in serum from pigs infected with the porcine whipworm, Trichuris suis. AB - microRNAs (miRNAs) are recently discovered as key regulators of gene translation and are becoming increasingly recognized for their involvement in various diseases. This study investigates the miRNA profile in pig serum during the course of an infection with the gastrointestinal parasite, Trichuris suis. Of this panel, the expression of selected miRNAs in serum from T. suis infected and uninfected pigs were determined by quantitative real time PCR using Exiqon Human Panel assays at 0, 2, 4, 6, 8 and 10 weeks post first infection (wpi). One miRNA, ssc-let-7d-3p, was significantly up-regulated in infected pigs 8 wpi. Interestingly, ssc-let-7d-3p shows high complementary to tsu-let-7a, which is the most highly transcribed miRNA in T. suis. The let-7 family miRNAs have been shown to post-transcriptionally regulate the translation of the helminth-controlling cytokine, IL-13, in a murine model for asthma and we hypothesize possible interactions between these host- and parasite-derived miRNAs and their immunomodulating roles. PMID- 27198774 TI - Evaluation of high-throughput assays for in vitro drug susceptibility testing of Tritrichomonas foetus trophozoites. AB - Tritrichomonas foetus is a sexually transmitted protozoan parasite that causes abortions in cattle and results in severe economic losses. In the United States, there are no safe and effective treatments for this parasite and infected animals are typically culled. In order to expedite drug discovery efforts, we investigated in vitro trophozoite killing assays amenable to high-throughput screening in 96 well plate formats. We evaluated the reduction of resorufin, incorporation of propidium iodide, and a luminescence-based ATP detection assay. Of these methods, reduction of resorufin was found to be the most reliable predictor of trophozoite concentrations. We further validated this method by conducting dose-response experiments suitable for calculation of EC50 values for two established compounds with known activity against trophozoites in vitro, namely, metronidazole and ronidazole. Our results demonstrate that the resorufin method is suitable for high-throughput screening and could be used to enhance efforts targeting new treatments for bovine trichomoniasis. PMID- 27198775 TI - Metarhizium anisopliae for controlling Rhipicephalus microplus ticks under field conditions. AB - Metarril SP Organic is a product based on the fungus Metarhizium anisopliae, which was developed for controlling agricultural pests. The present study evaluated the effect of Metarril SP Organic plus 10% mineral oil, for controlling Rhipicephalus microplus under field conditions. Three groups were formed: Control group, which received no treatment; Oil control group, which was bathed only with water, Tween 80 and mineral oil; and Metarril group, bathed in the oil-based formulation Metarril SP Organic. Two treatments per group were performed and to verify the effect of the treatments, all R. microplus ticks between 4.5 and 8.0mm in length on the left side of the cattle were counted on days +7, +14 and +21 after each treatment, and a sample of engorged females was collected for evaluation of biological parameters. The Metarril SP Organic oil formulation showed efficacy ranging from 8.53 to 90.53%. The average efficacy of the oil based formulation of Metarril SP Organic was 75.09 and 46.59% compared with the groups Control and Oil control, respectively. There were no significant changes in biological parameters of engorged R. microplus females collected from animals. Although there was no significant difference in the amount of ticks between the Oil control and Metarril groups, it is believed that the association of mineral oil with Metarril SP Organic product is effective in R. microplus tick control in field. Thus, this association has potential to be used in strategic control programs of cattle tick. PMID- 27198777 TI - Accuracy and precision of alternative estimators of ectoparasiticide efficacy. AB - While there is consensus that the efficacy of parasiticides is properly assessed using the Abbott formula, there is as yet no general consensus on the use of arithmetic versus geometric mean numbers of surviving parasites in the formula. The purpose of this paper is to investigate the accuracy and precision of various efficacy estimators based on the Abbott formula which alternatively use arithmetic mean, geometric mean and median numbers of surviving parasites; we also consider a maximum likelihood estimator. Our study shows that the best estimators using geometric means are competitive, with respect to root mean squared error, with the conventional Abbott estimator using arithmetic means, as they have lower average and lower median root mean square error over the parameter scenarios which we investigated. However, our study confirms that Abbott estimators using geometric means are potentially biased upwards, and this upward bias is substantial in particular when the test product has substandard efficacy (90% and below). For this reason, we recommend that the Abbott estimator be calculated using arithmetic means. PMID- 27198776 TI - In vitro and in vivo action of Piptadenia viridiflora (Kunth) Benth against Haemonchus contortus in sheep. AB - Anthelminthic resistant populations of Haemonchus contortus are a major problem in sheep rearing, but plant extracts may offer viable alternative treatments. In our preliminary studies, Piptadenia viridiflora was frequently selected by sheep grazing in the Cerrado. The present research evaluated its in vitro and in vivo anthelmintic activity. The HPLC chromatograms of P. viridiflora aqueous extract (AE) and ethanolic extract (EE) showed the presence of flavonoids. The total condensed tannin (proanthocyanidin) was 0.2 and 1.01% in AE and EE, respectively. In an egg hatching inhibition (EHI) test, the LC90 of AE was 2.4mg/mL, and, of EE, was 2.1mg/mL. After tannin extraction, higher EHI and lower LC90 were observed. In a larval development inhibition test, the LC90 of AE was 13.66mg/g of fecal culture. The highest dose of AE administered to mice (203.0mg/kg bw) was well tolerated, suggesting low toxicity. In vivo, AE was orally administered to lambs at 283mg/kg bw, and, at weeks one, two, and three post-treatment, the mean fecal egg count (FEC) was significantly lower than in untreated lambs (P<0.05). Blood parameters were normal and similar in untreated and treated sheep. For all lamb groups, the mean total serum protein was significantly higher at week two post-treatment than at other evaluated periods (P<0.05). Piptadenia viridiflora extracts had low condensed tannin content and exhibited high anthelminthic efficacy in vitro and significantly reduced FEC. Tannins were not shown to be the principal components affecting EHI, hence it is necessary to isolate and characterize the principal active P. viridiflora compounds, and to assess their possible synergism. PMID- 27198778 TI - First insights into the genetic diversity of Echinococcus granulosus sensu stricto (s.s.) in Serbia. AB - Cystic echinococcosis (CE) caused by Echinococcus granulosus sensu stricto (s.s.) is a cosmopolitan zoonotic infection which is endemic in Serbia where it is subject to mandatory reporting. However, information on the incidence of the disease in humans and prevalence of hydatid infection in livestock remains limited. We used sequenced data of the cytochrome c oxidase subunit 1 (cox 1) mitochondrial gene to examine the genetic diversity and population structure of E. granulosus (s.s.) from intermediate hosts from Serbia. We also compared our generated nucleotide sequences with those reported for neighbouring European countries. Echinococcus canadensis was molecularly confirmed from pig and human hydatid isolates. E. granulosus (G1) was confirmed from sheep and cattle hydatid isolates as well as the first molecular confirmation in Serbia of E. granulosus G2 in sheep and E. granulosus G3 in sheep and cattle hydatid isolates. The Serbian E. granulosus (s.s.) parsimony network displayed 2 main haplotypes (SB02 and SB05) which together with the neutrality indices were suggestive of bottleneck and/or balancing selection. Haplotype analysis showed the presence of the common E. granulosus haplotype described from other worldwide regions. Investigation of the pairwise fixation (Fst) index suggested that Serbian populations of E. granulosus (s.s.) from sheep and cattle hosts showed moderate genetic differentiation. Six of the Serbian haplotypes (SB02-SB07) were shared with haplotypes from Bulgaria, Hungary and/or Romania. Further studies using a larger number of hydatid isolates from various locations across Serbia will provide more information on the genetic structure of E. granulosus (s.s.) within this region. PMID- 27198780 TI - Assessment of resistance risk to fipronil and cross resistance to other insecticides in the Musca domestica L. (Diptera: Muscidae). AB - Fipronil, a phenyl-pyrazole insecticide has been used frequently for the control of disease vector house flies, Musca domestica L., (Diptera: Muscidae) worldwide including Pakistan. This experiment was performed to determine the selection and assessment of fipronil resistance evolution along with cross resistance to other three insecticides. After 26 generations of selection, the house fly strain developed 430-fold resistance to fipronil compared to a susceptible strain. Realized heritability (h(2)) of resistance to fipronil was 0.05. The projected rate of resistance development revealed that if 30-90% house flies were selected then a tenfold increase in lethal concentration 50 happened after 95.51-26.59 generations for fipronil (h(2)=0.05, Slope=2.34). At similar slope, if h(2)=0.15, then 31.84-8.86 generations are required for tenfold increase in LC50 at 30-90% selection intensity, respectively. Likewise, if h(2)=0.25, then similar would occur in 19.10-5.32 generations. Differences in any of the variable would affect the rate of resistance development. Selection with fipronil did not increase the level of resistance to lambda-cyhalothrin, profenofos and indoxacarb, suggesting no cross resistance to these insecticides. The results of our study concluded that house flies have the potential to develop resistances following continued selection pressure with fipronil. PMID- 27198779 TI - Red fox (Vulpes vulpes) as a potential reservoir host of cardiorespiratory parasites in Bosnia and Herzegovina. AB - Red fox (Vulpes vulpes) is considered as reservoir of different cardiorespiratory parasites of veterinary and medical importance. Since data on cardiorespiratory parasites in foxes in Bosnia and Herzegovina are still lacking, the aims of the present study were to (i) investigate the prevalence and geographical distribution of these parasites, (ii) determine genetic diversity of detected parasite species, and (iii) to estimate the role of foxes in the transmission cycle to companion animals and humans. Four species, morphologically and molecularly identified as Eucoleus boehmi (64.6%; 51/79), Eucoleus aerophilus (69.7%; 154/221), Crenosoma vulpis (45.7%; 101/221) and Linguatula serrata (1.3%; 1/79) were retrieved from nasal cavity and lungs in 184 (83.3%) animals. The occurrence of heartworms, Angiostrongylus vasorum and Dirofilaria immitis was not detected by necropsy or PCR. Furthermore, three distinct haplotypes of E. aerophilus (I, III, XV) and two of C. vulpis (I, II) previously reported in pet animals and wild carnivores were confirmed in this study. A new haplotype of C. vulpis (designated as haplotype V) was also identified based on 12S rRNA gene for the first time. The present study indicates a high prevalence and wide distribution of nasal and lung nematodes in fox population in Bosnia and Herzegovina, and supports the existence of transmission patterns between wildlife and pet animals. PMID- 27198781 TI - Comparative evaluation of recombinant HSP70 (N & C-terminal) fragments in the detection of equine trypanosomosis. AB - Trypanosomosis (Surra) is an economically important disease caused by Trypanosoma evansi which is an extracellular parasite present in the plasma, tissues and other body fluids of a wide range of hosts including domesticated animals. Currently, serological reports are based on detection of antibodies by ELISA using whole cell lysate (WCL) antigen, which has a limitation of persistence of anti-trypanosomal antibodies after successful treatment of the disease. Moreover, it has some ethical issues also like requirement of mice for in vivo maintenance of parasite for preparing the antigen. Therefore, in the present study, an attempt was made to evaluate the in vitro production of recombinant heat shock protein 70 (HSP70) for detection of antibodies in experimentally infected ponies. The amino acid sequence analysis of HSP70 revealed that N-terminal region of the protein was highly conserved while the C-terminal region was most divergent. The four different regions of HSP70 protein viz. HSP-1, HSP-2, HSP-3 and HSP-4 were cloned and expressed, among which HSP-1 (N-terminal region) & HSP-2 (C-terminal region) were truncated while HSP-3 & HSP-4 were complete C-terminal proteins. The recombinant fragments were probed with sequentially pooled experimental serum samples where antibodies were detected in these fragments from 10(th) day post infection till the termination of the experiment. Further, these recombinant fragments were also comparatively evaluated with WCL antigen in ELISA using experimental as well as field serum samples. It was observed that after successful treatment of infected ponies, there was a sharp fall in antibodies (within 90 days) when tested with recombinant HSP's fragments, while antibodies persisted even after 469 days when tested against WCL antigen. The sensitivity and specificity of all HSP70 fragments were also estimated from field serum samples with reference to WCL antigen ELISA. The HSP-1 showed minimum sensitivity (41.03%) among all the recombinant fragments. Among the C-terminal fragments, maximum sensitivity was observed with the HSP-2 (61.54%) while minimum was observed with HSP-4 (48.72%). The specificity increases for recombinant fragments from N-terminal to C-terminal region of protein and maximum specificity was observed with HSP-4 fragment (91.3%). PMID- 27198782 TI - Toxoplasma gondii and Neospora caninum in wild small mammals: Seroprevalence, DNA detection and genotyping. AB - Generally, rodents and other small mammals are considered as one of the sources of Toxoplasma gondii or Neospora caninum infection for cats and dogs as the definitive hosts of these two parasites, respectively. The aim of the study was to find out the prevalence of these two parasites in wild small mammals from the Czech Republic and to characterize T. gondii isolates by methods of molecular biology. A total of 621 wild small mammals were caught in the Czech Republic during years 2002-2014. Antibodies to T. gondii were detected by latex agglutination test in six (2.5%) of 240 small mammals (in two A. agrarius and four A. flavicollis). Antibodies to N. caninum were detected by commercially available competitive-inhibition enzyme-linked immunosorbent assay in one A. flavicolis (0.4%). Three of 427 (0.7%) liver samples were positive for T. gondii by PCR while negative for N. caninum. All embryo samples (n=102) were negative for both T. gondii and N. caninum. The three liver samples positive for T. gondii DNA (two from A. flavicollis and one from A. sylvaticus) were genotyped by 15 microsatellite markers and characterized as type II. To our knowledge, this is the first information about genetic characterization of T. gondii isolates in small mammals from Europe and the first detection of N. caninum antibodies in wild rodents from the Czech Republic. PMID- 27198783 TI - First report of Metastrongylus pudendotectus by the genetic characterization of mitochondria genome of cox1 in pigs from Tibet, China. AB - Lungworms, a world wild distributed parasites cause serious respiratory diseases to the pigs. A high infection rate of Metastrongylus lungworms has been found in Tibetan pigs being slaughtered in different slaughter houses of Tibet autonomous region. The main aim of our study was to detect and confirm the lungworm parasite by the genetic characterization of mitochondrial cox1genome isolated from the lungs of Tibetan pig. The adult lungworms were collected from the lungs of slaughtered pigs and identification was done through morphological examinations. Total genomic DNA of the extracted worms was performed and a fragment (~450bp) of the cox1 of mitochondrial (mt) gene was amplified. Amplicons were cloned into PGEM((r))-T Easy vector and the positive clones were sequenced from a commercial company. Sequence and phylogenetic analysis were performed by software of DNAMAN and MEGA respectively. The results revealed that the lungworms infecting the Tibetan pigs were Metastrongylus pudendotectus (M. pudendotectus). To our knowledge, this is the first report for the isolation and identification for the genetic characterization of mitochondria (mt) genome of cox1 of M. pudendotectus derived from Tibetan pigs in Tibet, China. PMID- 27198785 TI - Oxidative stress associated with pathological changes in the pancreas of cattle naturally infected by Eurytrema coelomaticum. AB - Although Eurytrema coelomaticum is considered a parasite with low pathogenicity, it may be associated with mortality and loss of productive performance in animals due to chronic pancreatitis. The aim of this study was to evaluate the occurrence of oxidative stress caused by E. coelomaticum in naturally infected cattle, correlating the biochemical findings with the parasite load and histopathological changes. For this study, blood and pancreas samples from 51 cattle were collected, and levels of the thiobarbituric acid reactive substances (TBARS), advanced oxidation protein products (AOPP) and ferric reducing ability of plasma (FRAP) were measured in the serum and pancreas, and superoxide dismutase (SOD) activity was measured in total blood. Parasite burden was determined opening the pancreatic ducts, and then fragments of pancreas were collected and fixed in 10% buffered formalin and routinely processed for histopathology. From the 51 collected pancreas, 33 (63.5%) were parasitized. The average parasite burden per pancreas was 532 (12-2,578). TBARS and FRAP showed higher levels in serum and pancreas of infected animals (p<0.05), with a positive correlation between the histopathological changes and the number of parasites. SOD level in blood was 42% higher in parasitized group compared with control group (p<0.05), as well as AOPP in serum. Based on these results, we concluded that in natural infection by E. coelomaticum in cattle, oxidative stress occurs, characterized by the occurrence of protein oxidation, lipid peroxidation and activation of antioxidant system. PMID- 27198784 TI - Glyceraldehyde 3-phosphate dehydrogenase and galectin from Dirofilaria immitis participate in heartworm disease endarteritis via plasminogen/plasmin system. AB - The interaction between parasitic protozoa and helminths, both in the blood and in tissues and the fibrinolytic system of their hosts is usually considered as a survival parasite mechanism since this system is the physiological route responsible for degrading fibrin clots. The broad-range proteolytic activity of plasmin, the final enzyme of the route, implies that its recruitment by these parasites is an important mechanism that mediates their invasion and establishment in the hosts. However, recent studies have proposed a dual role for plasmin by linking its over-production with pathological mechanisms at vascular level. Most of these studies have been conducted in Dirofilaria immitis, a blood borne parasite that survives in the pulmonary arteries of its host for years while it produces a chronic inflammatory disease, whose main pathogenic mechanism is the appearance of proliferative endarteritis. Recently, the participation of two proteins from D. immitis, glyceraldehyde 3-phosphate dehydrogenase (DiGAPDH) and galectin (DiGAL), in the activation of the fibrinolytic system of its host has been demonstrated, which has been a priori associated with parasite survival mechanisms. The aim of the present paper was to study the role of plasmin generated by these proteins in the emergence of proliferative endarteritis. An in vitro model of canine endothelial and smooth muscle cells, as well as the two parasitic recombinant proteins were employed. The results show that DiGAPDH and DiGAL stimulate the proliferation and migration of both cell types, as well as the degradation of the extracellular matrix (ECM) via plasminogen (PLG)/plasmin system, being all of these mechanisms related to the appearance of proliferative endarteritis. Due to the high degree of evolutionary conservation of these antigens, these data support the hypothesis of the survival/pathology ambivalence in the interactions between parasites and the fibrinolytic system of their hosts and represent an advance in the knowledge of the mechanisms involved in the emergence of proliferative endarteritis in the cardiopulmonary dirofilariosis (heartworm disease). PMID- 27198786 TI - Modelling Cooperia oncophora: Quantification of key parameters in the parasitic phase. AB - Cooperia oncophora is one of the most common intestinal nematodes in cattle. It is also the dose-limiting species for the most frequently used anthelmintics, and consequently, the species usually involved in reports of anthelmintic resistance. However, little information is available on its population dynamics, hindering the parameterisation of transmission models to support understanding of the impact of anthelmintic resistance, climate change and alternative control strategies on nematode epidemiology. This systematic review and meta-analysis provides estimates for key life history traits of the parasitic phase of C. oncophora and investigates potential influences of acquired immunity on these traits. PMID- 27198787 TI - Immunoproteomic and bioinformatic approaches to identify secreted Leishmania amazonensis, L. braziliensis, and L. infantum proteins with specific reactivity using canine serum. AB - Leishmania spp have a wide range of hosts, and each host can harbor several Leishmania species. Dogs, for example, are frequently infected by Leishmania infantum, where they constitute its main reservoir, but they also serve as hosts for L. braziliensis and L. amazonensis. Serological tests for antibody detection are valuable tools for diagnosis of L. infantum infection due to the high levels of antibodies induced, unlike what is observed in L. amazonensis and L. braziliensis infections. Likewise, serology-based antigen-detection can be useful as an approach to diagnose any Leishmania species infection using different corporal fluid samples. Immunogenic and secreted proteins constitute powerful targets for diagnostic methods in antigen detection. As such, we performed immunoproteomic (2-DE, western blot and mass spectrometry) and bioinformatic screening to search for reactive and secreted proteins from L. amazonensis, L. braziliensis, and L. infantum. Twenty-eight non-redundant proteins were identified, among which, six were reactive only in L. amazonensis extracts, 10 in L. braziliensis extracts, and seven in L. infantum extracts. After bioinformatic analysis, seven proteins were predicted to be secreted, two of which were reactive only in L. amazonensis extracts (52kDa PDI and the glucose-regulated protein 78), one in L. braziliensis extracts (pyruvate dehydrogenase E1 beta subunit) and three in L. infantum extracts (two conserved hypothetical proteins and elongation factor 1-beta). We propose that proteins can be suitable targets for diagnostic methods based on antigen detection. PMID- 27198788 TI - Xenodiagnosis on dogs with visceral leishmaniasis: Canine and sand fly aspects related to the parasite transmission. AB - One of the main limitations for the effective control of canine leishmaniasis in endemic areas is the difficulty in identifying infectious dogs. The objective of this study was to determine factors, related to dogs and to parasite detection in sand flies, which are associated with the positive xenodiagnosis of Leishmania infantum using the vector Lutzomyia longipalpis. The xenodiagnosis was performed in 50 owned dogs residing in endemic areas, which were divided into three different groups: G1-26 dogs proved to be infected and classified by severity of VL clinical signs on physical examination; G2-15 dogs proved to be infected and classified by severity of clinical signs and intensity of laboratory abnormalities; G3-nine dogs that were seropositive for anti-Leishmania IgG in ELISA tests. Parasite search in the sand flies after having fed on dogs in the xenodiagnosis was performed by both methodologies, PCR and dissection followed by microscopy. In G1, 58% (15/26) of dogs were able to transmit Leishmania to the vector, when parasite detection in sand flies were performed by PCR technique, 5 days after blood meal, whereas in G2, 53% (8/15) transmitted the parasite to the vector, however, confirmation was performed by direct observation of parasite through optical miscroscopy held 10 days after blood meal. Rate of infectiousness of dogs to sand flies was positively associated to severity of disease (p=0.042 and p=0.040), regardless the method used for clinical classification or for parasite detection in sand flies after xenodiagnosis. In G1 30% (3/10) of dogs with subclinical infection were infectious to the vector, while 80% (12/16) of dogs with clinical disease were also infectious. Even more, 17% (1/6) of dogs that had moderate disease were infectious to the sand flies, while 78% (7/9) of dogs with severe disease were infectious in G2. Still in G2, the proportion of sand flies infected (grade of infectiousness) was significantly lower (p=0.0098) when they fed on dogs with moderate disease (1%) in comparison with dogs with severe disease (38%). The dogs from G3 presented a rate of infectiousness of 11% (1/9), demonstrating that the indirect ELISA is not a good indicator of infectiousness and, therefore, should not be used as a confirmatory test for the euthanasia of dogs, as it is currently done in Brazil. PMID- 27198789 TI - Involvement of TLR6 in the induction of COX-2, PGE2 and IL-10 in macrophages by lipids from virulent S2P and attenuated R1A Babesia bovis strains. AB - Toll like receptors (TLRs) are involved in the modulation of diverse host genes expression through a complex network of signalling events that allow for an appropriate response to a microbial pathogen. In the present work we used TLR6KO mice in order to study the role of TLR6 in the immune discrimination of lipids from two Babesia bovis strains, attenuated R1A (LA) and virulent S2P (LV), and the consequent macrophage activation. We demonstrated that TLR6 is required for lipid body induction in murine peritoneal macrophages by both LA and LV. Interestingly, as regards IL-10 and COX-2/PGE2 pathway induction by LA and LV, we observed differences in the biological effects produced by these lipid extracts. Our results indicate a role of TLR6 in the down-modulation of these immunoregulators only in the case of LA, whereas this receptor was not implicated in pro-inflammatory TNFalpha, IL-6 and KC release induced by LA. Remarkably, LV did not exert the down-modulatory effect observed for LA, supporting the notion that LA and LV possess different lipid composition that could correlate with the polar pathogenic effect of both B. bovis strains. PMID- 27198790 TI - In vitro production of Trypanosoma equiperdum antigen and its evaluation for use in serodiagnosis of dourine. AB - A modified Baltz's in vitro cultivation system for the propagation of Trypanosoma equiperdum strain OVI was established to develop a replacement for the conventional production procedure of dourine diagnostic antigen in rats. To increase trypanosome yields we designed an optimized culture medium by addition of supplemental compounds. Trypanosomes were adapted to this medium by two succeeding cultivation steps which led to a substantial proliferation rate and an increased cell density tolerance, respectively. As a result, adapted parasites could be propagated to maximum cell densities of >2*10(6) cells/ml, facilitating in vitro antigen production in preparative quantities comparable to the conventional method. A panel of 180 horse field sera, previously sent for testing to the German National Reference Laboratory for Dourine, was tested by complement fixation test using culture-derived as well as conventionally produced dourine antigen. Cohen's kappa values for results obtained with two batches of culture derived antigen as compared to conventional antigen were 0.91 (95% confidence interval [CI]: 82.2-99.7) and 0.83 (95% CI: 70.3-95.3), respectively. Performance of antigens for diagnostic purposes was characterized in an inter-laboratory comparative study deploying 14 sera from horses with defined dourine statuses. Complement fixation test results from 15 participating European laboratories showed a diagnostic sensitivity of 94.1% (95% CI: 89.4-98.7) and a diagnostic specificity of 96.2% (95% CI: 92.5-99.9) for conventional antigen and a slightly higher diagnostic sensitivity of 96.0% (95% CI: 92.2-99.8) and a diagnostic specificity of 97.1% (95% CI: 94.0-100) for culture-derived antigen. We conclude that our novel approach for dourine antigen production from in vitro-grown trypanosomes described and evaluated herein meets the requirements for the prospective purpose in quantitative and qualitative terms and should be considered by the competent authorities as an alternative for the animal experiment currently prescribed by international standards. PMID- 27198791 TI - Corrigendum to "Objective evaluation of two deworming regimens in young Thoroughbreds using parasitological and performance parameters" [Vet. Parasitol. 221 (2016) 69-75]. PMID- 27198792 TI - Comparison of emergence traps of different shape and translucency in the trapping of Culicoides (Diptera: Ceratopogonidae). AB - Various types of emergence traps are available for investigations of the breeding habitats of Culicoides (Diptera: Ceratopogonidae). In order to assess the potential impact of the trap design on the trapping success, we compared the efficiency of opaque and white (more translucent) emergence traps and two trap shapes (cone-shaped and quadratic), to sample Culicoides emerging from cowpats. Significantly higher numbers of Culicoides chiopterus and Culicoides dewulfi were trapped with opaque traps, while there was no obvious effect of the trap shape. There were no distinct differences in the microclimate among different trap types. PMID- 27198793 TI - Pathology, immunohistochemistry, and ultrastructural findings associated with neurological sarcocystosis in cattle. AB - Paraffin-embedded blocks of brain of a nine months old bull calf that died of neurological signs in 1982 in Germany were restudied. Numerous schizonts and merozoites were found associated with extensive but focal necrosis and severe meningoencephalitis. Developing stages of schizonts as well as free merozoites were identified. The schizonts were primarily in perivascular areas. Ultrastructurally, schizonts were seen both in capillaries and in extravascular space. Merozoites were often concentrated in adventitial layers of capillaries. Schizonts divided by endopolygeny, the nucleus became multi-lobed, and at the terminal stage nuclear lobes were incorporated into budding merozoites. Individual merozoites were seen in neurons, astrocytes, oligodendrocytes, leukocytes, and vascular endothelial cells. Occasionally merozoites were present in the nucleus of mononuclear cells. Individual merozoites were ovoid, 3-5*2-3MUm in size, and contained a prominent nucleus, numerous micronemes, a conoid, but no rhoptries. Schizonts and merozoites did not react to polyclonal rabbit Neospora caninum, Toxoplasma gondii, and Sarcocystis neurona antibodies but did react to Sarcocystis cruzi antibodies. Because of morphological characteristics and the type of lesions, the parasite was likely due to an unidentified Sarcocystis species, different from S. cruzi. PMID- 27198794 TI - Potential role for mucosal IgA in modulating Haemonchus contortus adult worm infection in sheep. AB - Haemonchus contortus (H. contortus) is a haematophagous parasite which causes important economic losses in small ruminants. On the island of Gran Canaria, two sheep breeds coexist which differ in their susceptibility to the infection with H. contortus; the resistant Canaria Hair Breed (CHB) sheep and the susceptible Canaria Sheep (CS) breed. The major target of resistance mechanisms in CHB sheep are directed to the adult parasite stage, reducing the worm burden, and decreased length and fecundity of surviving worms. Mucosal IgA (mIgA) has been shown to be an important regulator of immunity in Haemonchus and Teladorsagia infections; through correlations with larval stages where such mechanisms as antibody dependent cell cytotoxicity and enzyme inhibition may mediate resistance. Here for the first time, we demonstrate a significant negative correlation between mIgA and adult worm length and fecundity only in the resistant CHB sheep. In contrast, and as reported in other sheep breeds, mIgA was only negatively correlated against the larval stage in the more susceptible CS breed. This study suggests mIgA may play a role in resistance to both larval and adult stages. PMID- 27198795 TI - First isolation and genotyping of Toxoplasma gondii from free-range chickens on Sao Luis island, Maranhao state, Brazil, with a new genotype described. AB - Toxoplasma gondii is a protozoan with worldwide distribution that infects warm blooded vertebrates, including humans. Toxoplasma is considered to be monospecific, but three classical clonal lineages (Types I-III) have been described, especially for isolates from North America and Europe. However, recently, several studies have shown that many isolates, particularly from South America, are different from the classic types and highly diverse, with the presence of specific clonal lineages and non-archetypal genotypes. In order to isolate and genotypically characterize T. gondii, 60 free-range naturally infected chickens (Gallus domesticus) from four municipalities on Sao Luis island, state of Maranhao, Brazil, were first serologically screened for IgG anti T. gondii antibodies by means of the immunofluorescent antibody test (IFAT>=1:16). Heart and brain samples from seropositive chickens were bioassayed in mice. The isolates obtained from bioassaying were genotyped by means of PCR RFLP (restriction fragment length polymorphism) using 11 markers and by microsatellites (MS) using 15 markers. The frequency of anti-T. gondii antibodies in the chickens examined was 25.0% (15/60). Five isolates of T. gondii were obtained and named TgCkBrMA1 to 5. Four genotypes were described. One of them is reported for the first time. No classic clonal lineages of types I, II or III were found, but the Brazilian clonal lineage BrI was identified. MS analysis revealed five genotypes. The results corroborate studies already developed in other regions of Brazil, thus indicating that T. gondii has high genetic diversity in Brazil. PMID- 27198796 TI - Pathological and ultrastructural observations and liver function analysis of Eimeria stiedai-infected rabbits. AB - To study the pathogenicity of Eimeria stiedai, sporulated oocysts were given orally to coccidian-free two-month-old New Zealand rabbits(1000+/-20g). After 30days, blood samples from the rabbit hearts were collected for routine blood tests, liver functions and four characteristics of blood coagulation. Additionally, specimens of the liver, bile duct and duodenum were collected to observe the changes in pathology and ultrastructure. E. stiedai severely restricted the growth and development of rabbits. Blood tests showed that glutamine transferase (GGT) and serum cholinesterase (ChE) were significantly different from the non-infected controls. Other extremely significant differences were observed in the biochemical indices of routine blood tests, liver function and four blood coagulation characteristics, indicating that the liver functions were significantly affected. Staining showed that, compared with the negative control group, the liver, bile duct and duodenum contained significant numbers of lesions, and organs and cell structures suffered severe damage in ultrastructure, which greatly affecting bodily functions. E. stiedai-infected rabbits model was successfully established, which might provide a theoretical basis for research on the pathogenesis of rabbit coccidia, and the diagnosis and prevention of coccidiosis in rabbits. PMID- 27198797 TI - Culex pipiens as a potential vector for transmission of Dirofilaria immitis and other unclassified Filarioidea in Southwest Spain. AB - Dirofilaria immitis is one of the most frequently detected mosquito-transmitted zoonotic filarioid nematode in mammals in Europe, being canine dirofilariosis a major animal health problem, endemic in the Mediterranean area. This study, focused on Southwest Spain, in order to bring new insights into (i) the epidemiology of Dirofilaria spp., (ii) the species of Culicid vectors possibly involved in their transmission and (iii) the genetic variability of those potential vectors. A total of 881 adult female mosquitoes from 11 different species, were captured during 2012-2013, and detection of filarioid DNA was attempted by PCR using specific primers (ITS-2 and COI), followed by DNA sequencing. In a single Culex pipiens specimen D. immitis DNA was detected both in the head-thorax and abdomen sections. Filarioid nematode DNA was also detected in eight additional Cx. pipiens specimens also in both the thorax and the abdomen, but analysis of sequence data did not allow unambiguous assignment of any of the obtained sequences to a previously defined species. All Cx. pipiens with filarioid DNA were individually analysed by CQ11 to discriminate between pipiens, molestus, and hybrid forms. Besides, rDNA ITS-2 sequence analysis revealed the presence of haplotype H1 and H2 of Cx. pipiens. To our knowledge this study revealed, for the first time in Spain, the occurrence of likely mature infection of D. immitis in Cx. pipiens, as well as with other yet uncharacterized nematodes, supporting its role as a potential vector of these filarids. PMID- 27198798 TI - Morphology and genetic variability within Taenia multiceps in ruminants from Italy. AB - The aim of this study was to investigate the genetic variability and population structure of Taenia multiceps, and to correlate morphological features of individual coenuri with haplotypes. A total of 92 animals (86 sheep; 4 goats; 1 cattle; 1 mouflon, Ovis musimon) aged between 6-36 months showing clinical symptoms of cerebral coenurosis were included in this study. T. multiceps coenuri (n=118) sampled from live animals during routine surgery procedures or at post mortem inspections were examined morphologically and molecularly identified. Morphological features of the 52 coenuri selected for this study (number and size of large and small hooks) were within the range reported in the literature. Fifty two of the molecularly confirmed T. multiceps coenuri harboured by 47 animals (sheep=41; cattle=1; goats=4; mouflon=1) were used to determine gene genealogies and population genetic indices and were compared to the 3 T. multiceps genetic variants, Tm1-Tm3 previously described from Sardinia, Italy. For the 379 bp cox1 dataset we identified 11 polymorphic sites of which 8 were parsimony informative. A high haplotype diversity (0.664+/-0.067) was recorded for the cox1 sequences defining 10 haplotypes (TM01-TM10). The comparison of haplotypes generated in this study with published T. multiceps Tm1 variant pointed to the possible existence of a common lineage for T. multiceps. No correlation was detected between the size of the small and large hooks and the cox 1 haplotypes. Polycystic infestation (2-9 coenuri) was recorded in 27.7% of animals (13/47). No statistical correlation between polycystic T. multiceps infection and haplotypes was detected. PMID- 27198800 TI - Vertical transmission and fetal damage in animal models of congenital toxoplasmosis: A systematic review. AB - In humans, the probability of congenital infection and fetal damage due to Toxoplasma gondii is dependent on the gestation period at which primary infection occurs. Many animal models have been used for vaccine, drug testing, or studies on host or parasite factors that affect transmission or fetal pathology, but few works have directly tested fetal infection and damage rates along gestation. So, the purpose of this work was to perform a systematic review of the literature to determine if there is a model which reflects these changes as they occur in humans. We looked for papers appearing between 1970 and 2014 in major databases like Medline and Scopus, as well as gray literature. From almost 11,000 citations obtained, only 49 papers fulfilled the criteria of having data of all independent variables and at least one dependent datum for control (untreated) groups. Some interesting findings could be extracted. For example, pigs seem resistant and sheep susceptible to congenital infection. Also, oocysts cause more congenitally infected offspring than tissue cysts, bradyzoites or tachyzoites. In spite of these interesting findings, very few results on vertical transmission or fetal damage rates were similar to those described for humans and only for one of the gestation thirds, not all. Moreover, in most designs tissue cysts - with unknown number of bradyzoites - were used, so actual dose could not be established. The meta-analysis could not be performed, mainly because of great heterogeneity in experimental conditions. Nevertheless, results gathered suggest that a model could be designed to represent the increase in vertical transmission and decrease in fetal damage found in humans under natural conditions. PMID- 27198799 TI - Is the infectiousness of dogs naturally infected with Trypanosoma cruzi associated with poly-parasitism? AB - Interactions among different species of parasites co-infecting the same host could be synergistic or antagonistic. These interactions may modify both the frequency of infected hosts and their infectiousness, and therefore impact on transmission dynamics. This study determined the infectiousness of Trypanosoma cruzi-seropositive dogs (using xenodiagnosis) and their parasite load (quantified by qPCR), and tested the association between both variables and the presence of concomitant endoparasites. A cross-sectional serosurvey conducted in eight rural villages from Pampa del Indio and neighboring municipalities (northeastern Argentina) detected 32 T. cruzi-seropositive dogs out of 217 individuals examined for infection. Both the infectiousness to the vector Triatoma infestans and parasite load of T. cruzi-seropositive dogs examined were heterogeneous. A statistically significant, nine-fold higher mean infectiousness was registered in T. cruzi-seropositive dogs co-infected with Ancylostoma caninum and a trematode than in T. cruzi-seropositive dogs without these infections. The median parasite load of T. cruzi was also significantly higher in dogs co-infected with these helminths. An opposite trend was observed in T. cruzi-seropositive dogs that were serologically positive to Toxoplasma gondii or Neospora caninum relative to dogs seronegative for these parasites. Using multiple logistic regression analysis with random effects, we found a positive and significant association between the infectiousness of T. cruzi-seropositive dogs and co-infections with A. caninum and a trematode. Our results suggest that co-infections may be a modifier of host infectiousness in dogs naturally infected with T. cruzi. PMID- 27198801 TI - The prevalence, abundance and distribution of cyathostomins (small stongyles) in horses from Western Romania. AB - Forty seven working horses from Romania were post-mortem examined for small strongyles (Cyathostominae) infections. All horses were found infected. The overall cyathostomins intensity ranged from 390 to 13,010 and horses were infected by 8-24 species. The intensity was higher in ventral colon (1531) and dorsal colon (824), the lowest in the caecum (524). Twenty four species were identified. Cyathostomum catinatum, Cylicocyclus insigne, and C. Nassatus had 100% of prevalence. Over 50% of horses were infected by Coronocyclus coronatus, Cylicostephanus calicatus, C. goldi, and C. longibursatus. Other prevalent species (34%-45%) were Cyathostomum tetracanthum, Cylicostephanus minutus and Gyalocephalus capitatus. Coronocyclus labiatus, Parapoteriostomum mettami, Poteriostomum imparidentatum and P. ratzii had the lowest prevalence. Most species showed high organ preference with a niche breadth value between 1 and 1.96 while only 7 species (Coronocyclus labiatus, Cyathostomum tetracanthum, C. brevicapsulatus, Cylicocyclus elongatus, C. insigne, C. leptostomum and C. radiatus) showed a more generalist selection. The niche breadth of 10 species was significantly (p<0.05) influenced by itself intensity (Coronocyclus labratus, Cyathostomum pateratum, C. tetracanthum, Cylicocyclus elongatus, C. radiatus, C. ultrajectinus, C. leptostomum, Cylicodontophorus euproctus, Poteriostomum imparidentatum, P. ratzii). The niche breadth of Cylicocyclus nassatus was positively (p<0.05) influenced by the summed intensity of the other species while that of Cylicocyclus elongatus was negatively (p<0.05) influenced by the intensity of the other species. The cluster analysis of the Cyathostominae community composition showed a major cluster composed by the three dominant species, followed by a cluster composed by Coronocyclus coronatus, while all the other species presented a tree like structure. PMID- 27198802 TI - Aberrant Ancylostoma sp. in the brain of a dog. AB - A 14-month-old, male American Bulldog presented to Texas A&M University Veterinary Medical Teaching Hospital in August of 2012 for anorexia, hydrophobia and gradually worsening neurologic signs. Grossly hemorrhage on the left side of the caudal cerebrum and cerebellum was observed and histologically corresponded with necrohemorrhagic and lymphoplasmacytic encephalitis associated with adult nematodes. Based on morphology and molecular analysis, these were identified as Ancylostoma sp. PMID- 27198803 TI - Trypanosoma teixeirae: A new species belonging to the T. cruzi clade causing trypanosomosis in an Australian little red flying fox (Pteropus scapulatus). AB - Little is known about the genetic diversity and pathogenicity of trypanosomes in Australian bats. Recently a novel trypanosome species was identified in an adult female little red flying fox (Pteropus scapulatus) with clinical and pathological evidence of trypanosomosis. The present study used morphology and molecular methods to demonstrate that this trypanosome is a distinct species and we propose the name Trypanosoma teixeirae sp. n. Morphological comparison showed that its circulating trypomastigotes were significantly different from those of Trypanosoma pteropi and Trypanosoma hipposideri, two species previously described from Australian bats. Genetic information was not available for T. pteropi and T. hipposideri but phylogenetic analyses at the 18S ribosomal RNA (rRNA) and glycosomal glyceraldehyde phosphate dehydrogenase (gGAPDH) loci indicated that T. teixeirae sp. n. was genetically distinct and clustered with other bat-derived trypanosome species within the Trypanosoma cruzi clade. PMID- 27198804 TI - The uremic toxin oxythiamine causes functional thiamine deficiency in end-stage renal disease by inhibiting transketolase activity. AB - Decreased transketolase activity is an unexplained characteristic of patients with end-stage renal disease and is linked to impaired metabolic and immune function. Here we describe the discovery of a link to impaired functional activity of thiamine pyrophosphate cofactor through the presence, accumulation, and pyrophosphorylation of the thiamine antimetabolite oxythiamine in renal failure. Plasma oxythiamine was significantly increased by 4-fold in patients receiving continuous ambulatory peritoneal dialysis and 15-fold in patients receiving hemodialysis immediately before the dialysis session (healthy individuals, 0.18 [0.11-0.22] nM); continuous ambulatory peritoneal dialysis patients, 0.64 [0.48-0.94] nM; and hemodialysis patients (2.73 [1.52-5.76] nM). Oxythiamine was converted to the transketolase inhibitor oxythiamine pyrophosphate. The red blood cell oxythiamine pyrophosphate concentration was significantly increased by 4-fold in hemodialysis (healthy individuals, 15.9 nM and hemodialysis patients, 66.1 nM). This accounted for the significant concomitant 41% loss of transketolase activity (mU/mg hemoglobin) from 0.410 in healthy individuals to 0.240 in hemodialysis patients. This may be corrected by displacement with excess thiamine pyrophosphate and explain lifting of decreased transketolase activity by high-dose thiamine supplementation in previous studies. Oxythiamine is likely of dietary origin through cooking of acidic thiamine containing foods. Experimentally, trace levels of oxythiamine were not formed from thiamine degradation under physiologic conditions but rather under acidic conditions at 100( degrees )C. Thus, monitoring of the plasma oxythiamine concentration in renal failure and implementation of high-dose thiamine supplements to counter it may help improve the clinical outcome of patients with renal failure. PMID- 27198805 TI - Better together for better dementia research and care. PMID- 27198807 TI - Food Fraud and Adulteration, a Centuries-old Practice. PMID- 27198806 TI - Central Line Associated Blood Stream Infections in Pediatric Hematology/Oncology Patients With Different Types of Central Lines. AB - BACKGROUND: Central line associated bloodstream infections (CLABSIs) are a significant cause of morbidity and mortality in pediatric hematology/oncology (PHO) patients. Understanding the differences in CLABSI rates by central line (CL) type is important to inform clinical decisions. PROCEDURE: CLABSI, using similar definitions, noted with three commonly used CL types (totally implanted catheter [port], tunneled externalized catheter [TEC], peripherally inserted central catheter [PICC]) and CL-specific line days were prospectively tracked across 15 US PHO centers from May 2012 until April 2015 and CLABSI rates (CLABSI per 1,000 CL-specific line days) were calculated. Host and organism characterstics associated with the CLABSI events were analyzed. RESULTS: Over the course of 2.8 million line days, 1,113 CLABSI events (397 in inpatients and 716 in ambulatory patients) were noted. The inpatient CLABSI rate was higher than the ambulatory CLABSI rate for each of the CL types: 1.48 versus 0.16 for ports, 3.51 versus 1.38 for TECs, and 3.07 versus 1.16 for PICCs, respectively. TECs and PICCs were associated with higher CLABSI rates than ports, inpatient and ambulatory. CONCLUSIONS: We found that CLABSI rates were significantly higher for inpatients compared to ambulatory PHO patients for all CL types. Among ambulatory patients, TECs had the highest CLABSI rate and ports the lowest. Among inpatients, TECs and PICCs had higher CLABSI rates than ports but were not statistically different from one another. Cognizant that host and underlying disease attributes may contribute to these differences, these results can still inform CL choice in clinical practice. PMID- 27198808 TI - Food Fraud Prevention: Policy, Strategy, and Decision-Making - Implementation Steps for a Government Agency or Industry. AB - This paper addresses the role of governments, industry, academics, and non governmental organizations in Food Fraud prevention. Before providing strategic concepts for governments and authorities, definitions of Food Fraud are reviewed and discussed. Next there is a review of Food Fraud activities by the Global Food Safety Initiative (GFSI), the Elliott Review in the United Kingdom, the European Commission resolution on Food Fraud, and the US Food Safety Modernization Act including the Preventative Controls Rule. Two key concepts for governments or a company are: (1) formally, and specifically, mention food fraud as a food issue and (2) create an enterprise-wide Food Fraud prevention plan. The research includes a case study of the implementation of the concepts by a state or provincial agency. This analysis provides a foundation to review the role of science and technology in detection, deterrence and then contributing to prevention. PMID- 27198809 TI - Food Adulteration: From Vulnerability Assessment to New Analytical Solutions. AB - Crises related to the presence of melamine in milk or horse meat in beef have been a wake-up call to the whole food industry showing that adulteration of food raw materials is a complex issue. By analysing the situation, it became clear that the risk-based approach applied to ensure the safety related to chemical contaminants in food is not adequate for food fraud. Therefore, a specific approach has been developed to evaluate adulteration vulnerabilities within the food chain. Vulnerabilities will require the development of new analytical solutions. Fingerprinting methodologies can be very powerful in determining the status of a raw material without knowing the identity of each constituent. Milk adulterated by addition of adulterants with very different chemical properties could be detected rapidly by Fourier-transformed mid-infrared spectroscopy (FT mid-IR) fingerprinting technology. In parallel, a fast and simple multi-analytes liquid-chromatography tandem mass-spectrometry (LC/MS-MS) method has been developed to detect either high levels of nitrogen-rich compounds resulting from adulteration or low levels due to accidental contamination either in milk or in other sensitive food matrices. To verify meat species authenticity, DNA-based methods are preferred for both raw ingredients and processed food. DNA macro array, and more specifically the Meat LCD Array have showed efficient and reliable meat identification, allowing the simultaneous detection of 32 meat species. While the Meat LCD Array is still a targeted approach, DNA sequencing is a significant step towards an untargeted one. PMID- 27198810 TI - Food Adulteration in Switzerland: From 'Ravioli' over 'Springbok' to 'Disco Sushi'. AB - The driving force behind food adulteration is monetary profit and this has remained unchanged for at least the last hundred years. Food adulterations were and still are difficult to uncover because they occur mostly in an unpredictable and unexpected way. Very often food falsifiers take advantage of modern technology in such a way that food adulterations are difficult or sometimes even impossible to detect. Targets for food adulteration were and still are highly priced food items such as spirits, meat, seafood and olive oil. Although difficult to detect, food adulterations were in the past strong driving forces for the development of adequate detection methods in the official food control laboratories and for the enforcement of the food law. A very prominent example in this context is the 'Ravioli scandal' in Switzerland in the late 1970s which showed that cheap second-class meat could be processed into products without being discovered for long time. As a consequence the official food control laboratories in Switzerland were reinforced with more laboratory equipment and technical staff. With the introduction of new detection principles such as DNA based analytical methods new kinds of food adulteration could and can be uncovered. Analytical methods have their limits and in some cases of food fraud there are no analytical means to detect them. In such cases the examination of trade by checking of accounts is the method of choice. PMID- 27198811 TI - Use of Isotope Ratio Determination (13C/12C) to Assess the Production Method of Sparkling Wine. AB - The production of a sparkling wine can be performed with different methods taking from a few weeks to several years, which often justifies a difference in added value for the consumer. This paper presents the use of isotope ratio delta(13)C measurements combined with physico-chemical analyses for the determination of mislabelling of sparkling wines produced by 'ancestral', 'traditional', 'closed tank' or 'gasification' methods. This work shows that the isotope composition of CO(2) compared with that of the corresponding dried residue of wine (DRW) can assess whether carbonate CO(2) in a sparkling wine originates from alcohol fermentation or from artificial gas addition. Isotopic ratios expressed as delta(13)C(CO2) and delta(13)C(DRW) measurements have been obtained for each wine by gasbench isotopic ratio mass spectroscopy and cavity ring down infrared spectroscopy, respectively. When the difference between delta(13)C(CO2) and delta(13)C(DRW) is negative, the presence of artificial CO(2) can be undoubtedly inferred, which would exclude the production methods 'ancestral' or 'traditional' for instance. Other parameters such as alcohol content, sugar and acid distributions are also important to complete the analytical panel to aid fraud tracking. PMID- 27198812 TI - Locally Grown, Natural Ingredients? The Isotope Ratio Can Reveal a Lot! AB - This communication gives an overview of selected isotope analyses applied to food authenticity assessment. Different isotope ratio detection technologies such as isotope ratio mass spectrometry (IRMS) and cavity ring down spectroscopy (CRDS) are briefly described. It will be explained how delta(18)O of water contained in fruits and vegetables can be used to assess their country of production. It will be explained why asparagus grown in Valais, in the centre of the Alps carries much less heavy water than asparagus grown closer to the sea coast. On the other hand, the use of delta(13)C can reveal whether a product is natural or adulterated. Applications including honey or sparkling wine adulteration detection will be briefly presented. PMID- 27198813 TI - Lactic Acid Bacteria as Markers for the Authentication of Swiss Cheeses. AB - The manufacture of traditional Swiss-type cheeses adheres to strict rules, so as to guarantee quality and purity of the end product. This raises production costs and means consumers pay more. It also opens the door to cut-rate forgeries claiming to be made to the stringent standards and causing considerable economic losses to the entire dairy sector. In order to combat product counterfeiting, Agroscope has developed proof-of-origin cultures that allow the identification of copycats. Carefully selected lactic acid bacteria, having uniquely located insertion sequence elements, are proliferated by fermentation and subsequently dried by lyophilization. The proof-of-origin culture is added during the cheese production process and sustains maturation. These so-called 'biological markers' can be traced using polymerase chain reaction (PCR) methods, which allow authentication even if the cheese is cut into pieces or grated. They do not lead to any alteration of the cheese's taste or texture, and are compatible with the strict 'protected designation of origin' (PDO) specifications. The proof-of origin cultures are used for the protection of several traditional Swiss-cheese varieties, such as Emmental PDO, Tete de Moine PDO, and Appenzeller((r)). A market survey of Emmental PDO showed that the system is effective in revealing fraud and has the power to enforce corrective measures. PMID- 27198814 TI - Basmati Rice Fraud under the Magnifying Glass of DNA Analysis. AB - Basmati rice is a perfumed rice of high commercial value which is easily adulterated. A list of rice varieties accepted as true Basmati is the subject of an agreement between Europe, Pakistan and India. Each rice variety can be characterized by DNA profiling, thus offering to the control authorities a powerful tool to detect fraud. Mixtures of authentic Basmati and non-Basmati varieties can be quantified. During the last six years, about one third of the analysed samples proved to be fraudulent. PMID- 27198815 TI - Chemical Analysis: An Indispensable Means for Uncovering Severe Cases of Fraud with Cosmetics and Tattoo Inks. AB - Three cases of fraud with commodities containing illegal stealth compounds are presented, which were uncovered by the State Laboratory Basel-City, Switzerland. All three commodities, grapefruit seed extracts, a phytocosmetical skin cream, and tattoo inks, were produced abroad, had forged declarations of ingredients and, in the case of the extracts and the cream, were marketed with far-reaching health claims. While inspections will identify suspicious products and would be able to eliminate health claims to some extent, only chemical analysis can uncover the illegal agents used and give law enforcement bodies the necessary evidence to immediately clamp down on those brands, where the stealth agent presents a serious health hazard to consumers. PMID- 27198816 TI - Protocatechuic Acid Levels Discriminate Between Organic and Conventional Wheat from Denmark. AB - Organic wheat retails at higher market prices than the conventionally grown counterparts. In view of fair competition and sustainable consumer confidence, the organic nature of organic wheat needs to be assured. Amongst other controls this requires analytical tests based on discriminating traits. In this paper, phenolic acids were examined by liquid chromatography analysis as biomarkers for discriminating between the two groups by means of a controlled grown full factorial design Danish wheat sample set. By combining baseline and retention time correction pre-treatments and principal component analysis, discrimination between organic and conventional produce was found to be expressed in the first principal component (93%), whilst the second principal component accounted for the production year (4%). Upon examination of the loadings plot, a single chromatographic peak was found to account for a large part in the discrimination between the two wheat production systems. This was further underpinned by statistically significant differences found in concentrations between the organic and conventional production systems of this phenolic acid (ANOVA, P<0.05). The phenolic acid was tentatively identified as protocatechuic acid by negative mode mass spectrometry. The results obtained implied that protocatechuic acid may serve as a single marker for discrimination between organic and conventional produced wheat. PMID- 27198819 TI - Synthesis and Electrophoretic Properties of Novel Nanoparticles for Colored Electronic Ink and e-Paper Applications. AB - A new approach based on non-pigmented, stable colored nanoparticles able to migrate upon application of an electrical field (10-60 V) has been developed for the improvement of the color brightness of e-displays. The scientific challenges comprised the development of efficient syntheses of tri- and bifunctional dendrimers including branching points for further extension and individual decoration with dye (yellow, magenta, cyan). The covalent attachment of these scaffolds to silica nanoparticles was performed via hydrosilylation and final in situ charging generated attractive silica shells for the substractive CMY color space model. PMID- 27198820 TI - Biosorption at the HES-SO Valais-Wallis Sion Looking for Partners to Implement Innovative Technologies. AB - Water pollution contributes to a number of health problems and disorders in humans, and dramatically affects wild animals and the environment as a whole. Biosorption is a sound and sustainable way to remove pollutants like metals, dyes, phenols, pesticides or drug metabolites from liquid effluents. But despite active research worldwide, technical limitations still impede its widespread use. At HES-SO Valais-Wallis in Sion, Prof. Simon Crelier is working on the development of efficient, economically viable and scalable biosorption processes. PMID- 27198824 TI - Organically modified titania having a metal catalyst: a new type of liquid-phase hydrogen-transfer photocatalyst working under visible light irradiation and H2 free conditions. AB - Organically modified titania having a metal catalyst (OMTC), 2,3 dihydroxynaphthalene-modified titania having palladium metal, successfully worked as a hydrogen-transfer (C[double bond, length as m-dash]C hydrogenation) photocatalyst in the presence of triethanolamine as the hydrogen source under visible light irradiation and hydrogen-free conditions. PMID- 27198823 TI - Maladaptive mood repair, atypical respiratory sinus arrhythmia, and risk of a recurrent major depressive episode among adolescents with prior major depression. AB - BACKGROUND: Because depressive illness is recurrent, recurrence prevention should be a mainstay for reducing its burden on society. One way to reach this goal is to identify malleable risk factors. The ability to attenuate sadness/dysphoria (mood repair) and parasympathetic nervous system functioning, indexed as respiratory sinus arrhythmia (RSA), are impaired during depression and after it has remitted. The present study therefore tested the hypothesis that these two constructs also may mirror risk factors for a recurrent major depressive episode (MDE). METHOD: At time 1 (T1), 178 adolescents, whose last MDE had remitted, and their parents, reported on depression and mood repair; youths' RSA at rest and in response to sad mood induction also were assessed. MDE recurrence was monitored until time 2 (T2) up to 2 years later. Mood repair at T1 (modeled as a latent construct), and resting RSA and RSA response to sadness induction (RSA profile), served to predict onset of first recurrent MDE by T2. RESULTS: Consistent with expectations, maladaptive mood repair predicted recurrent MDE, above and beyond T1 depression symptoms. Further, atypical RSA profiles at T1 were associated with high levels of maladaptive mood repair, which, in turn, predicted increased risk of recurrent MDE. Thus, maladaptive mood repair mediated the effects of atypical RSA on risk of MDE recurrence. CONCLUSIONS: This study documented that a combination of behavioral and physiological risk factors predicted MDE recurrence in a previously clinically referred sample of adolescents with depression histories. Because mood repair and RSA are malleable, both could be targeted for modification to reduce the risk of recurrent depression in youths. PMID- 27198822 TI - Polydopamine-Mediated Immobilization of Alginate Lyase to Prevent P. aeruginosa Adhesion. AB - Given alginate's contribution to Pseudomonas aeruginosa virulence, it has long been considered a promising target for interventional therapies, which have been performed by using the enzyme alginate lyase. In this work, instead of treating pre-established mucoid biofilms, alginate lyase is immobilized onto a surface as a preventive measure against P. aeruginosa adhesion. A polydopamine dip-coating strategy is employed for functionalization of polycarbonate surfaces. Enzyme immobilization is confirmed by surface characterization. Surfaces functionalized with alginate lyase exhibit anti-adhesive properties, inhibiting the attachment of the mucoid strain. Moreover, surfaces modified with this enzyme also inhibit the adhesion of the tested non-mucoid strain. Unexpectedly, treatment with heat inactivated enzyme also inhibits the attachment of mucoid and non-mucoid P. aeruginosa strains. These findings suggest that the antibacterial performance of alginate lyase functional coatings is catalysis-independent, highlighting the importance of further studies to better understand its mechanism of action against P. aeruginosa strains. PMID- 27198825 TI - Do patient-reported measures of symptoms and health status predict mortality in hemodialysis? An assessment of POS-S Renal and EQ-5D. AB - Introduction Experience with the use of patient-reported outcome measures such as EQ-5D and the symptom module of the Palliative care Outcome Scale-Renal Version (POS-S Renal) as mortality prediction tools in hemodialysis is limited. Methods A prospective survival study of people receiving hemodialysis (N = 362). The EQ-5D and the POS-S Renal were used to assess symptom burden and self-rated health (with a self-rated component). Participants were followed from instrument completion to death or study end. Competing risks survival analysis was used to evaluate associations with time to death, with renal transplant as a competing risk. Findings 32% (N = 116) of participants died over a median (25th-75th centile) of 2.6 (1.41-3.38) years. Factors most notably associated with mortality adjusted hazard ratio (95%CI) included: lower EQ VAS score 2.7 (1.4, 5.2) P = 0.004 (lowest tertile), higher POS-S Renal score 2.4 (1.3, 4.3) P = 0.004 (highest tertile), and lower EQ-5D score 2.6 (1.3, 5.3) P = 0.01 (lowest tertile) as well as the presence of: "problems with mobility?" 2 (1.1, 3.3) P = 0.01, or "problems with usual activities?" 2.1 (1.4, 3.3), P < 0.001. After age adjustment area under the receiver operating curves (AUC) (95%CI) for mortality were: 0.71 (0.62, 0.79) for EQ VAS score, 0.71 (0.63, 0.80) for POS-S Renal-S Renal score, and 0.76 (0.68, 0.84) for EQ-5D score. AUC 95%CI was highest for our fourth model at 0.79 (0.72, 0.86) comprised of individual elements from both instruments and established risk factors. Discussion EQ VAS scores and predictive models based on combinations of elements from the POS-S Renal and EQ-5D instruments may aid in mortality discrimination and possibly in the delivery of supportive care services. PMID- 27198826 TI - Insights into seasonal dynamics of bacterial meningitis. PMID- 27198827 TI - Bridging the knowledge gap for ocular surface squamous neoplasia: Africa and beyond. PMID- 27198828 TI - Task shifting rheumatic heart disease screening to non-experts. PMID- 27198829 TI - Building health systems in fragile states: the instructive example of Afghanistan. PMID- 27198830 TI - Peruvian lessons for the transition from MDGs to SDGs. PMID- 27198831 TI - Universal health coverage: political courage to leave no one behind. PMID- 27198832 TI - Can India transition from informal abortion provision to safe and formal services? PMID- 27198833 TI - A vision for improved cancer screening in Nigeria. PMID- 27198834 TI - Supporting research leadership in Africa. PMID- 27198835 TI - Supporting research leadership in Africa. PMID- 27198836 TI - Alternative vector control methods to manage the Zika virus outbreak: more haste, less speed. PMID- 27198837 TI - Alternative vector control methods to manage the Zika virus outbreak: more haste, less speed. PMID- 27198838 TI - Alternative vector control methods to manage the Zika virus outbreak: more haste, less speed - Authors' reply. PMID- 27198839 TI - Level of evidence of verbal autopsy. PMID- 27198840 TI - Level of evidence of verbal autopsy - Authors' reply. PMID- 27198841 TI - Seasonal dynamics of bacterial meningitis: a time-series analysis. AB - BACKGROUND: Bacterial meningitis, which is caused mainly by Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae, inflicts a substantial burden of disease worldwide. Yet, the temporal dynamics of this disease are poorly characterised and many questions remain about the ecology of the disease. We aimed to comprehensively assess seasonal trends in bacterial meningitis on a global scale. METHODS: We developed the first bacterial meningitis global database by compiling monthly incidence data as reported by country-level surveillance systems. Using country-level wavelet analysis, we identified whether a 12 month periodic component (annual seasonality) was detected in time-series that had at least 5 years of data with at least 40 cases reported per year. We estimated the mean timing of disease activity by computing the centre of gravity of the distribution of cases and investigated whether synchrony exists between the three pathogens responsible for most cases of bacterial meningitis. FINDINGS: We used country-level data from 66 countries, including from 47 countries outside the meningitis belt in sub-Saharan Africa. A persistent seasonality was detected in 49 (96%) of the 51 time-series from 38 countries eligible for inclusion in the wavelet analyses. The mean timing of disease activity had a latitudinal trend, with bacterial meningitis seasons peaking during the winter months in countries in both the northern and southern hemispheres. The three pathogens shared similar seasonality, but time-shifts differed slightly by country. INTERPRETATION: Our findings provide key insight into the seasonal dynamics of bacterial meningitis and add to knowledge about the global epidemiology of meningitis and the host, environment, and pathogen characteristics driving these patterns. Comprehensive understanding of global seasonal trends in meningitis could be used to design more effective prevention and control strategies. FUNDING: Princeton University Health Grand Challenge, US National Institutes of Health (NIH), NIH Fogarty International Center Research and Policy for Infectious Disease Dynamics programme (RAPIDD), Bill & Melinda Gates Foundation. PMID- 27198842 TI - Topical fluorouracil after surgery for ocular surface squamous neoplasia in Kenya: a randomised, double-blind, placebo-controlled trial. AB - BACKGROUND: Ocular surface squamous neoplasia (OSSN) is an aggressive eye tumour particularly affecting people with HIV in Africa. Primary treatment is surgical excision; however, tumour recurrence is common. We assessed the effect of fluorouracil 1% eye drops after surgery on recurrence. METHODS: We did this multicentre, randomised, placebo-controlled trial in four centres in Kenya. We enrolled patients with histologically proven OSSN aged at least 18 years. After standard surgical excision, participants were randomly allocated to receive either topical fluorouracil 1% or placebo four times a day for 4 weeks. Randomisation was stratified by surgeon, and participants and trial personnel were masked to assignment. Patients were followed up at 1 month, 3 months, 6 months, and 12 months. The primary outcome was clinical recurrence (supported by histological assessment where available) by 1 year, and analysed by intention to treat. The sample size was recalculated because events were more common than anticipated, and trial enrolment was stopped early. The trial was registered with Pan-African Clinical Trials Registry (PACTR201207000396219). FINDINGS: Between August, 2012, and July, 2014, we assigned 49 participants to fluorouracil and 49 to placebo. Four participants were lost to follow-up. Recurrences occurred in five (11%) of 47 patients in the fluorouracil group and 17 (36%) of 47 in the placebo group (odds ratio 0.21, 95% CI 0.07-0.63; p=0.01). Adjusting for passive smoking and antiretroviral therapy had little effect (odds ratio 0.23; 95% CI 0.07-0.75; p=0.02). Adverse effects occurred more commonly in the fluorouracil group, although they were transient and mild. Ocular discomfort occurred in 43 of 49 patients in the fluorouracil group versus 36 of 49 in the placebo group, epiphora occurred in 24 versus five, and eyelid skin inflammation occurred in seven versus none. INTERPRETATION: Topical fluorouracil after surgery substantially reduced recurrence of OSSN, was well-tolerated, and its use recommended. FUNDING: British Council for Prevention of Blindness and the Wellcome Trust. PMID- 27198843 TI - Focused cardiac ultrasound screening for rheumatic heart disease by briefly trained health workers: a study of diagnostic accuracy. AB - BACKGROUND: Echocardiographic screening for rheumatic heart disease (RHD) can identify individuals with subclinical disease who could benefit from antibiotic prophylaxis. However, most settings have inadequate resources to implement conventional echocardiography and require a feasible, accurate screening method. We aimed to investigate the accuracy of screening by non-expert operators using focused cardiac ultrasound (FoCUS). METHODS: In this prospective study of diagnostic accuracy, we recruited schoolchildren aged 5 to 15 years in Fiji to undergo two blinded tests. The index test was a FoCUS assessment of mitral and aortic regurgitation, performed by nurses after an 8-week training programme. The reference standard was the diagnosis of RHD by a paediatric cardiologist, based on a standard echocardiogram performed by a skilled echocardiographer. The primary outcome was the accuracy of the index test with use of the most sensitive criteria (any regurgitation). FINDINGS: We included 2004 children in the study. The index tests were done between September, 2012, and September, 2013, by seven nurses in eight schools in Fiji. The diagnostic accuracy of the screening test (area under receiver operator characteristic curve) was 0.89 (95% CI 0.83-0.94). When the primary cut-off point (any regurgitation) was used for analysis, sensitivity was 84.2% (72.1-92.5) and specificity was 85.6% (83.9-87.1). The sensitivity of individual nurses ranged from 66.7% to 100% and specificity 74.0% to 93.7%. INTERPRETATION: Screening by briefly trained nurses using FoCUS was accurate for the diagnosis of RHD. Refinements to training and screening test methods should be studied in a range of settings, and in parallel with investigations of the long-term clinical and cost-effectiveness of screening for RHD. FUNDING: Cure Kids, New Zealand; the Fiji Water Foundation provided funding for portable ultrasound equipment; see acknowledgments for further details of funders. PMID- 27198844 TI - Achieving maternal and child health gains in Afghanistan: a Countdown to 2015 country case study. AB - BACKGROUND: After the fall of the Taliban in 2001, Afghanistan experienced a tumultuous period of democracy overshadowed by conflict, widespread insurgency, and an inflow of development assistance. Although there have been several cross sectional assessments of health gains over the last decade, there has been no systematic analysis of progress and factors influencing maternal and child health in Afghanistan. METHODS: We undertook a comprehensive, systematic assessment of reproductive, maternal, newborn, and child health in Afghanistan over the last decade. Given the paucity of high-quality data before 2001, we relied mainly on 11 nationally representative surveys conducted between 2003 and 2013. We estimated national and subnational time trends for key reproductive, maternal, and child health indicators, and used linear regression methods to determine predictors of change in health-care service use. All analyses were weighted for sampling and design effects. Additional information was collated and analysed about health system performance from third party surveys and about human resources from the Afghan Ministry of Public Health. FINDINGS: Between 2003 and 2015, Afghanistan experienced a 29% decline in mortality of children younger than 5 years. Although definite reductions in maternal mortality remain uncertain, concurrent improvements in essential maternal health interventions suggest parallel survival gains in mothers. In a little over a decade (2003-13 inclusive), coverage of several maternal care interventions increased-eg, for antenatal care (16% to 53%), skilled birth attendance (14% to 46%), and births in a health facility (13% to 39%). Childhood vaccination coverage rates for the basic vaccines from the Expanded Programme of Immunisation (eg, BCG, measles, diphtheria-tetanus-pertussis, and three doses of polio) doubled over this period (about 40% to about 80%). Between 2005 and 2013, the number of deployed facility and community-based health-care professionals also increased, including for nurses (738 to 5766), midwives (211 to 3333), general physicians (403 to 5990), and community health workers (2682 to 28 837). Multivariable analysis of factors contributing to overall changes in skilled birth attendance and facility births suggests independent contributions of maternal literacy, deployment of community midwives, and proximity to a facility. INTERPRETATION: Despite conflict and poverty, Afghanistan has made reasonable progress in its reproductive, maternal, newborn, and child health indicators over the last decade based on contributions of factors within and outside the health sector. However, equitable access to health care remains a challenge and present delivery models have high transactional costs, affecting sustainability. To maintain and further accelerate health and development gains, future strategies in Afghanistan will need to focus on investments in improving social determinants of health and targeted cost effective interventions to address major causes of maternal and newborn mortality. FUNDING: US Fund for UNICEF under the Countdown to 2015 for Maternal, Newborn, and Child Survival grant from the Bill & Melinda Gates Foundation, and from the Government of Canada, Foreign Affairs, Trade and Development Canada. Additional direct and in-kind support was received from the UNICEF Country Office Afghanistan, the Centre for Global Child Health, the Hospital for Sick Children, Toronto, the Aga Khan University, and Mother and Child Care Trust (Pakistan). PMID- 27198845 TI - Child health and nutrition in Peru within an antipoverty political agenda: a Countdown to 2015 country case study. AB - BACKGROUND: Peru is an upper-middle-income country with wide social and regional disparities. In recent years, sustained multisectoral antipoverty programmes involving governments, political parties, and civil society have included explicit health and nutrition goals and spending increased sharply. We did a country case study with the aim of documenting Peru's progress in reproductive, maternal, neonatal, and child health from 2000-13, and explored the potential determinants. METHODS: We examined the outcomes of health interventions coverage, under-5 mortality, neonatal mortality, and prevalence of under-5 stunting. We obtained data from interviews with key informants, a literature review of published and unpublished data, national censuses, and governmental reports. We obtained information on social determinants of health, including economic growth, poverty, unmet basic needs, urbanisation, women's education, water supply, fertility rates, and child nutrition from the annual national households surveys and the Peruvian Demographic and Health Surveys. We obtained national mortality data from the Interagency Group for Child Mortality Estimation, and calculated subnational rates from 11 surveys. Analyses were stratified by region, wealth quintiles, and urban or rural residence. We calculated coverage indicators for the years 2000-13, and we used the Lives Saved Tool (LiST) to estimate the effect of changes in intervention coverage and in nutritional status on mortality. FINDINGS: From 2000 to 2013, under-5 mortality fell by 58% from 39.8 deaths per 1000 livebirths to 16.7. LiST, which was used to predict the decline in mortality arising from changes in fertility rates, water and sanitation, undernutrition, and coverage of indicators of reproductive, maternal, neonatal, and child health predicted that the under-5 mortality rate would fall from 39.8 to 28.4 per 1000 livebirths, accounting for 49.2% of the reported reduction. Neonatal mortality fell by 51% from 16.2 deaths per 1000 livebirths to 8.0. Stunting prevalence remained stable at around 30% until 2007, decreasing to 17.5% by 2013, and the composite coverage index for essential health interventions increased from 75.1% to 82.6%, with faster increases among the poor, in rural areas, and in the Andean region. Socioeconomic, urban-rural, and regional inequalities in coverage, mortality, and stunting were substantially reduced. The proportion of the population living below the poverty line reduced from 47.8% to 23.9%, women with fewer than 4 years of schooling reduced from 11.5% to 6.9%, urbanisation increased from 68.1% to 75.6%, and the total fertility rate decreased from 3.0 children per woman to 2.4. We interviewed 175 key informants and they raised the following issues: economic growth, improvement of social determinants, civil society empowerment and advocacy, out-of-health and within-health-sector changes, and sustained implementation of evidence-based, pro-poor reproductive, maternal, neonatal, and child health interventions. INTERPRETATION: Peru has made substantial progress in reducing neonatal and under-5 mortality, and child stunting. This country is a good example of how a combination of political will, economic growth, broad societal participation, strategies focused on poor people, and increased spending in health and related sectors can achieve significant progress in reproductive, maternal, neonatal, and child health. The remaining challenges include continuing to address inequalities in wealth distribution, poverty, and access to basic services, especially in the Amazon and Andean rural areas. FUNDING: Bill & Melinda Gates Foundation. PMID- 27198846 TI - Effects of pectin on fermentation characteristics, carbohydrate utilization, and microbial community composition in the gastrointestinal tract of weaning pigs. AB - SCOPE: We aimed to investigate the effects of three different soluble pectins on the digestion of other consumed carbohydrates, and the consequent alterations of microbiota composition and SCFA levels in the intestine of pigs. METHODS AND RESULTS: Piglets were fed a low-methyl esterified pectin enriched diet (LMP), a high-methyl esterified pectin enriched diet (HMP), a hydrothermal treated soybean meal enriched diet (aSBM) or a control diet (CONT). LMP significantly decreased the ileal digestibility of starch resulting in more starch fermentation in the proximal colon. In the ileum, low-methyl esterified pectin present was more efficiently fermented by the microbiota than high-methyl esterified pectin present which was mainly fermented by the microbiota in the proximal colon. Treated soybean meal was mainly fermented in the proximal colon and shifted the fermentation of cereal dietary fiber to more distal parts, resulting in high SCFA levels in the mid colon. LMP, HMP, and aSBM decreased the relative abundance of the genus Lactobacillus and increased that of Prevotella in the colon. CONCLUSION: The LMP, HMP, and aSBM, differently affected the digestion processes compared to the control diet and shaped the colonic microbiota from a Lactobacillus-dominating flora to a Prevotella-dominating community, with potential health-promoting effects. PMID- 27198847 TI - Small angle neutron scattering contrast variation reveals heterogeneities of interactions in protein gels. AB - We propose a quantitative approach to probe the spatial heterogeneities of interactions in macromolecular gels, based on a combination of small angle X-ray (SAXS) and neutrons (SANS) scattering. We investigate the structure of model gluten protein gels and show that the gels display radically different SAXS and SANS profiles when the solvent is (at least partially) deuterated. The detailed analysis of the SANS signal as a function of the solvent deuteration demonstrates heterogeneities of sample deuteration at different length scales. The progressive exchange between the protons (H) of the proteins and the deuteriums (D) of the solvent is inhomogeneous and 60 nm large zones that are enriched in H are evidenced. In addition, at low protein concentration, in the sol state, solvent deuteration induces a liquid/liquid phase separation. Complementary biochemical and structure analyses show that the denser protein phase is more protonated and specifically enriched in glutenin, the polymeric fraction of gluten proteins. These findings suggest that the presence of H-rich zones in gluten gels would arise from the preferential interaction of glutenin polymers through a tight network of non-exchangeable intermolecular hydrogen bonds. PMID- 27198849 TI - Overcoming Challenges in CAR T-cell Product CGMP Release. PMID- 27198852 TI - Multistage Delivery Technologies: Multifunctional, Interdisciplinary Approaches to Nanomedicine. PMID- 27198848 TI - A comprehensive tractography study of patients with bipolar disorder and their unaffected siblings. AB - BACKGROUND: Diffusion tensor imaging studies show reductions in fractional anisotropy (FA) in individuals with bipolar disorder and their unaffected siblings. However, the use of various analysis methods is an important source of between-study heterogeneity. Using tract-based spatial statistics, we previously demonstrated widespread FA reductions in patients and unaffected relatives. To better interpret the neuroanatomical pattern of this previous finding and to assess the influence of methodological heterogeneity, we here applied tractography to the same sample. METHODS: Diffusion-weighted images were acquired for 96 patients, 69 unaffected siblings and 56 controls. We applied TRACULA, an extension of a global probabilistic tractography algorithm, to automatically segment 18 major fiber tracts. Average FA within each tract and at each cross section along each tract was compared between groups. RESULTS: Patients had reduced FA compared to healthy controls and their unaffected siblings in general, and in particular in the parietal part of the superior longitudinal fasciculus. In unaffected siblings, FA was nominally reduced compared to controls in the corpus callosum. Point-wise analyses indicated that similar effects were present along extended sections, but with variable effect sizes. Current symptom severity negatively correlated with FA in several fronto-limbic association tracts. CONCLUSIONS: The differential sensitivity of analysis techniques likely explains between-study heterogeneity in anatomical localization of FA reductions. The present tractography analysis confirms the presence of overall FA reductions in patients with bipolar disorder, which are most pronounced in the superior longitudinal fasciculus. Unaffected siblings may display similar, albeit more subtle and anatomically restricted FA reductions. Hum Brain Mapp 37:3474-3485, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27198853 TI - Endogenous Transposase Source in Human Cells Mobilizes piggyBac Transposons. PMID- 27198854 TI - The Methylene Alkoxy Carbamate Self-Immolative Unit: Utilization for the Targeted Delivery of Alcohol-Containing Payloads with Antibody-Drug Conjugates. AB - A strategy for the conjugation of alcohol-containing payloads to antibodies has been developed and involves the methylene alkoxy carbamate (MAC) self-immolative unit. A series of MAC beta-glucuronide model constructs were prepared to evaluate stability and enzymatic release, and the results demonstrated high stability at physiological pH in a substitution-dependent manner. All the MAC model compounds efficiently released alcohol drug surrogates under the action of beta glucuronidase. To assess the MAC technology for ADCs, the potent microtubule disrupting agent auristatin E (AE) was incorporated through the norephedrine alcohol. Conjugation of the MAC beta-glucuronide AE drug linker to the anti-CD30 antibody cAC10, and an IgG control antibody, gave potent and immunologically specific activities in vitro and in vivo. These studies validate the MAC self immolative unit for alcohol-containing payloads within ADCs, a class that has not been widely exploited. PMID- 27198855 TI - Reducing-Agent-Free Instant Synthesis of Carbon-Supported Pd Catalysts in a Green Leidenfrost Droplet Reactor and Catalytic Activity in Formic Acid Dehydrogenation. AB - The development of green synthesis methods for supported noble metal catalysts remains important challenges to improve their sustainability. Here we first synthesized carbon-supported Pd catalysts in a green Leidenfrost droplet reactor without reducing agents, high-temperature calcination and reduction procedures. When the aqueous solution containing Pd nitrate precursor, carbon support, and water is dripped on a hot plate, vapor layer is formed between a solution droplet and hot surface, which allow the solution droplet to be levitated on the hot surface (Leidenfrost phenomena). Subsequently, Pd nanoparticles can be prepared without reducing agents in a weakly basic droplet reactor created by the Leidenfrost phenomena, and then the as-prepared Pd nanoparticles are loaded on carbon supports during boiling down the droplet on hot surface. Compared to conventional incipient wetness and chemical synthetic methods, the Leidenfrost droplet reactor does not need energy-consuming, time-consuming, and environmentally unfriendly procedures, which leads to much shorter synthesis time, lower carbon dioxide emission, and more ecofriendly process in comparison with conventional synthesis methods. Moreover, the catalysts synthesized in the Leidenfrost droplet reactor provided much better catalytic activity for room temperature formic acid decomposition than those prepared by the incipient wetness method. PMID- 27198856 TI - Curcumin-carboxymethyl chitosan (CNC) conjugate and CNC/LHR mixed polymeric micelles as new approaches to improve the oral absorption of P-gp substrate drugs. AB - The low oral bioavailability of numerous drugs has been mostly attributed to the significant effect of P-gp-mediated efflux on intestinal drug transport. Herein, we developed mixed polymeric micelles (MPMs) comprised of curcumin-carboxymethyl chitosan (CNC) conjugate, as a potential inhibitor of P-gp-mediated efflux and gastrointestinal absorption enhancer, and low-molecular-weight heparin-all-trans retinoid acid (LHR) conjugate, as loading material, with the aim to improve the oral absorption of P-gp substrate drugs. CNC conjugate was synthesized by chemical bonding of curcumin (Cur) and carboxymethyl chitosan (CMCS) taking advantage of the inhibition of intestinal P-gp-mediated secretion by Cur and the intestinal absorption enhancement by CMCS. The chemical structure of CNC conjugate was characterized by 1H NMR with a degree of substitution of Cur of 4.52-10.20%. More importantly, CNC conjugate markedly improved the stability of Cur in physiological pH. Cyclosporine A-loaded CNC/LHR MPMs (CsA-CNC/LHR MPMs) were prepared by dialysis method, with high drug loading 25.45% and nanoscaled particle size (~200 nm). In situ single-pass perfusion studies in rats showed that both CsA + CNC mixture and CsA-CNC/LHR MPMs achieved significantly higher Ka and Peff than CsA suspension in the duodenum and jejunum segments (p < 0.01), which was comparable to verapamil coperfusion effect. Similarly, CsA + CNC mixture and CsA-CNC/LHR MPMs significantly increased the oral bioavailability of CsA as compared to CsA suspension. These results suggest that CNC conjugate might be considered as a promising gastrointestinal absorption enhancer, while CNC/LHR MPMs had the potential to improve the oral absorption of P-gp substrate drugs. PMID- 27198857 TI - Arteriovenous oscillations of the redox potential: Is the redox state influencing blood flow? AB - OBJECTIVE: Studies on the regulation of human blood flow revealed several modes of oscillations with frequencies ranging from 0.005 to 1 Hz. Several mechanisms were proposed that might influence these oscillations, such as the activity of vascular endothelium, the neurogenic activity of vessel wall, the intrinsic activity of vascular smooth muscle, respiration, and heartbeat. These studies relied typically on non-invasive techniques, for example, laser Doppler flowmetry. Oscillations of biochemical markers were rarely coupled to blood flow. METHODS: The redox potential difference between the artery and the vein was measured by platinum electrodes placed in the parallel homonymous femoral artery and the femoral vein of ventilated anesthetized pigs. RESULTS: Continuous measurement at 5 Hz sampling rate using a digital nanovoltmeter revealed fluctuating signals with three basic modes of oscillations: ~ 1, ~ 0.1 and ~ 0.01 Hz. These signals clearly overlap with reported modes of oscillations in blood flow, suggesting coupling of the redox potential and blood flow. DISCUSSION: The amplitude of the oscillations associated with heart action was significantly smaller than for the other two modes, despite the fact that heart action has the greatest influence on blood flow. This finding suggests that redox potential in blood might be not a derivative but either a mediator or an effector of the blood flow control system. PMID- 27198858 TI - Frontal fibrosing alopecia: reflections and hypotheses on aetiology and pathogenesis. AB - Since first described by Kossard in 1994, frontal fibrosing alopecia (FFA) has been something of an enigma. The clinical heterogeneity of FFA, its apparent rarity and investigators' suboptimal access to phenotypically consistent patient cohorts may all have had a negative impact on delineating disease pathogenesis. Moreover, there is a relative paucity of epidemiological, interventional and basic research studies, and there have been no advances in translational therapeutics, unlike for other inflammatory dermatoses, such as alopecia areata (AA). Dermatologists anecdotally describe an increasing incidence in FFA over the last decade, which has led to the notion that the disorder may be induced by unknown environmental triggers. On the other hand, segregation of FFA in some families lends support to an unexplored genetic element implicated in disease pathogenesis. We herein review what is known about the pathobiology of FFA and formulate working hypotheses to advance insight into this intriguing hair disorder. PMID- 27198859 TI - The fundamentals behind solving for unknown molecular structures using computer assisted structure elucidation: a free software package at the undergraduate and graduate levels. AB - The successful elucidation of an unknown compound's molecular structure often requires an analyst with profound knowledge and experience of advanced spectroscopic techniques, such as Nuclear Magnetic Resonance (NMR) spectroscopy and mass spectrometry. The implementation of Computer-Assisted Structure Elucidation (CASE) software in solving for unknown structures, such as isolated natural products and/or reaction impurities, can serve both as elucidation and teaching tools. As such, the introduction of CASE software with 112 exercises to train students in conjunction with the traditional pen and paper approach will strengthen their overall understanding of solving unknowns and explore of various structural end points to determine the validity of the results quickly. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27198860 TI - Wolbachia endosymbionts in haplodiploid and diploid scolytine beetles (Coleoptera: Curculionidae: Scolytinae). AB - Haplodiploidy is a sex determination system in which fertilized diploid eggs develop into females and unfertilized haploid eggs develop into males. The evolutionary explanations for this phenomenon include the possibility that haplodiploidy can be reinforced by infection with endosymbiotic bacteria, such as Wolbachia. The subfamily Scolytinae contains species with haplodiploid and diploid sex determination systems. Thus, we studied the association with Wolbachia in 12 diploid and 11 haplodiploid scolytine beetles by analyzing wsp and multilocus sequence typing (MLST) of five loci in this endosymbiont. Wolbachia genotypes were compared with mitochondrial (COI) and nuclear (EF) genotypes in the scolytines. Eight of the 23 scolytine species were infected with Wolbachia, with haplodiploids at significantly higher rates than diploid species. Cloning and sequencing detected multiple infections with up to six Wolbachia strains in individual species. Phylogenetic analyses of wsp and five MLST genes revealed different Wolbachia strains in scolytines. Comparisons between the beetle and Wolbachia phylogenies revealed that closely related beetles were infected with genetically different Wolbachia strains. These results suggest the horizontal transmission of multiple Wolbachia strains between scolytines. We discuss these results in terms of the evolution of different sex determination systems in scolytine beetles. PMID- 27198862 TI - Is Health Literacy Associated With Depressive Symptoms Among Korean Adults? Implications for Mental Health Nursing. AB - OBJECTIVE: This study investigated whether health literacy is associated with depressive symptoms among Korean adults, when adjusting for relevant risk factors for depression. METHODS: Data were collected from a sample of 585 community dwelling Korean adults living in Seoul and Kwangju, South Korea, using a quota sampling strategy. A cross-sectional, multivariate regression analysis was used to investigate the association between health literacy and depressive symptoms. RESULTS: When controlled for covariates, a lower level of health literacy was significantly associated with a higher level of depressive symptoms. CONCLUSION: Health literacy may play an important role in preventing and treating depression. Future research is needed to determine if improving health literacy, through health promotion interventions, can enhance community-dwelling Korean adults' understanding of depressive symptoms and relevant treatment options. PMID- 27198861 TI - Outcome Trends after US Military Concussive Traumatic Brain Injury. AB - Care for US military personnel with combat-related concussive traumatic brain injury (TBI) has substantially changed in recent years, yet trends in clinical outcomes remain largely unknown. Our prospective longitudinal studies of US military personnel with concussive TBI from 2008-2013 at Landstuhl Regional Medical Center in Germany and twp sites in Afghanistan provided an opportunity to assess for changes in outcomes over time and analyze correlates of overall disability. We enrolled 321 active-duty US military personnel who sustained concussive TBI in theater and 254 military controls. We prospectively assessed clinical outcomes 6-12 months later in 199 with concussive TBI and 148 controls. Global disability, neurobehavioral impairment, depression severity, and post traumatic stress disorder (PTSD) severity were worse in concussive TBI groups in comparison with controls in all cohorts. Global disability primarily reflected a combination of work-related and nonwork-related disability. There was a modest but statistically significant trend toward less PTSD in later cohorts. Specifically, there was a decrease of 5.9 points of 136 possible on the Clinician Administered PTSD Scale (-4.3%) per year (95% confidence interval, 2.8-9.0 points, p = 0.0037 linear regression, p = 0.03 including covariates in generalized linear model). No other significant trends in outcomes were found. Global disability was more common in those with TBI, those evacuated from theater, and those with more severe depression and PTSD. Disability was not significantly related to neuropsychological performance, age, education, self reported sleep deprivation, injury mechanism, or date of enrollment. Thus, across multiple cohorts of US military personnel with combat-related concussion, 6-12 month outcomes have improved only modestly and are often poor. Future focus on early depression and PTSD after concussive TBI appears warranted. Adverse outcomes are incompletely explained, however, and additional studies with prospective collection of data on acute injury severity and polytrauma, as well as reduced attrition before follow-up will be required to fully address the root causes of persistent disability after wartime injury. PMID- 27198863 TI - Proteinuria as a Therapeutic Target in Advanced Chronic Kidney Disease: a Retrospective Multicenter Cohort Study. AB - Current evidence of proteinuria reduction as a surrogate target in advanced chronic kidney disease (CKD) is incomplete due to lack of patient-pooled database. We retrospectively studied a multicenter cohort of 1891 patients who were enrolled in the nationwide multidisciplinary pre-end stage renal disease care program with a baseline glomerular filtration rate (GFR) <45 mL/min/1.73 m(2) and followed longitudinally to investigate the effect of the change in proteinuria on renal death (defined as composite of dialysis and death occurring before initiation of dialysis). The group with a change in proteinuria <=0.30 g/g (n = 1261) had lower cumulative probabilities of renal death (p < 0.001). In a linear regression model, a higher baseline proteinuria and a greater increase in proteinuria were associated with faster annual GFR decline. Cox's analysis showed that every 1 unit increase in natural log(baseline proteinuria, 10 g/g) and every 0.1 g/g increase in the change in proteinuria resulted in 67% (HR = 1.67, 95% CI: 1.46-1.91) and 1% (HR = 1.01, 95% CI: 1.01-1.01) greater risk of renal death respectively after adjusting for the effects of the other covariates. Our study provided a patient-based evidence to support proteinuria as a therapeutic target in advanced CKD. PMID- 27198865 TI - Self-control as generalized operant behavior by adults with autism spectrum disorder. AB - The present investigation attempted to teach self-control to 3 adults who had been diagnosed with autism spectrum disorder. Using a self-control training procedure that coupled a gradual fading of delay to access a large delayed reinforcer with a concurrent work requirement, each participant was exposed to conditions in which baseline levels of choices for large delayed reinforcers and task engagement increased 10-fold. Furthermore, generalization effects were partially demonstrated in a novel context. PMID- 27198864 TI - Alternating Poly(ester-anhydride) by Insertion Polycondensation. AB - We report on a synthetic method where polyanhydride is used as starting material and the ester monomers are inserted through complete esterification, leading to an alternating ester-anhydride copolymer. The molar ratio of ricinoleic acid (RA) and sebacic acid (SA) was optimized until polysebacic acid is completely converted to carboxylic acid-terminated RA-SA and RA-SA-RA ester-dicarboxylic acids. These dimers and trimers were activated with acetic anhydride, polymerized under heat and vacuum to yield alternating RA-SA copolymer. The resulting alternating poly(ester-anhydride) have the RA at regular intervals. The regular occurrences of RA side chains prevent anhydride interchange, enhancing hydrolytic stability, which allows storage of the polymer at room temperature. PMID- 27198866 TI - Insect-specific flaviviruses in Aedes mosquitoes in Greece. AB - Mosquitoes of the genus Aedes are known vectors of pathogenic flaviviruses, and insect-specific flaviviruses (ISFs) have been detected in members of this genus in numerous parts of the world. In order to gain insight into whether Aedes mosquitoes in Greece are infected by flaviviruses, 1173 Aedes spp. mosquitoes collected in 2010 and 2012 were grouped in 53 pools and tested by RT nested PCR using flavivirus generic primers. Eight pools (15.09 %) were found to be PCR positive: five pools (5/53, 9.4 %) contained RNA sequences related to Ochlerotatus caspius flavivirus (OCFV), an ISF previously detected in the Iberian peninsula, two pools (2/53, 3.8 %) contained sequences related to a mosquito flavivirus detected in Aedes vexans (AeveV) in Italy and the Czech Republic, and one pool contained a DNA sequence that was too short to identify accurately. The highest OCFV prevalence (12.9 %) was observed in August 2010 in the regional unit of Thessaloniki. Similar sequences were later obtained from two Culex spp. pools collected in 2013 in the same regions. A genetic difference of 0.2-1.4 % was seen among the Greek OCFV strains, which differed by 2.2-4.1 % from the Iberian strains and by 6.2-11.1 % from the Finnish Hanko virus. The genetic distances among strains varied depending on the genome region (genes for E, NS3 and NS5 proteins), with NS3 being the most variable. The present study shows no evidence of infection of Aedes mosquitoes with known pathogenic flaviviruses, but it expands the geographic distribution of OCFV in the eastern Mediterranean area. Any implication of ISFs for public health (either directly or through interactions with other flaviviruses in the mosquitoes) remains to be elucidated. PMID- 27198867 TI - Near-infrared in vivo bioimaging using a molecular upconversion probe. AB - We demonstrate molecular upconversion probe, NRh-1, which shows excellent photostability, high quantum yield up to 1.8%, and rapid excretion capability. The NIR-to-NIR upconversion technique offers remarkably improved signal-to-noise ratios and substantially higher tissue penetration depth. PMID- 27198868 TI - Pay drug companies $1bn for each new antibiotic, says report. PMID- 27198869 TI - Assessment of the Physiological Adaptations to Chronic Hypoxemia in Eisenmenger Syndrome. AB - OBJECTIVE: Eisenmenger syndrome is characterized by severe and lifelong hypoxemia and pulmonary hypertension. Despite this, patients do surprisingly well and report a reasonable quality of life. The aim of this study was to investigate whether these patients undergo adaptation of their skeletal and cardiac muscle energy metabolism which would help explain this paradox. DESIGN AND SETTING: Ten patients with Eisenmenger syndrome and eight age- and sex-matched healthy volunteers underwent symptom-limited treadmill cardiopulmonary exercise testing, transthoracic echocardiography and (31) P magnetic resonance spectroscopy of cardiac and skeletal muscle. Five subjects from each group also underwent near infrared spectroscopy to assess muscle oxygenation. RESULTS: Despite having a significantly lower peak VO2 , patients with Eisenmenger syndrome have a similar skeletal muscle phosphocreatine (PCr) recovery, a measure of oxidative capacity, when compared to healthy controls (34.9 s +/- 2.9 s vs. 35.2 s +/- 1.7 s, P = .9). Furthermore their intracellular pH falls to similar levels during exercise suggesting they are not reliant on early anaerobic metabolism (0.3 +/- 0.06 vs. 0.28 +/- 0.04, P = .7). While their right ventricular systolic function remained good, the Eisenmenger group had a lower cardiac PCr/ATP ratio compared to the control group (1.55 +/- 0.10 vs. 2.17 +/- 0.15, P < .05). CONCLUSIONS: These results show that adult patients with Eisenmenger syndrome have undergone beneficial physiological adaptations of both skeletal and cardiac muscle. This may, in part, explain their surprisingly good survival despite a lifetime of severe hypoxemia and adverse cardiopulmonary hemodynamics. PMID- 27198871 TI - A short buttress plate fixation of posterior column through single ilioinguinal approach for complex acetabular fractures. AB - PURPOSE: The goal of this study was to evaluate the safety and efficacy of a new technique for posterior column fixation through the standard ilioinguinal approach. METHODS: We conducted a retrospective review involving 33 consecutive patients with complex acetabular fractures treated using a short buttress plate fixation of posterior column through single ilioinguinal approach. Radiographic evaluation was performed using criteria described by Matta. Functional outcome was assessed using modified Postel Merle D'Aubigne score. RESULTS: Between 2008 and 2013, 33 adult patients with mean age of 46 years and mean follow up of 37.5 months were enrolled. Anatomic reduction was obtained in 61 % of cases, imperfect reduction in 24 % of cases and poor reduction in 15 % of cases. The average modified Merle d'Aubigne score was 15: categorized as excellent in seven, good in 18, fair in three, and poor in four. One patient died at 15 days because of pulmonary embolism. Four patients sustained temporary lateral femoral cutaneous palsy. At final follow up, two patients had severe post-traumatic arthritis; one of them underwent a total hip arthroplasty at 93 months. None of the patients had loss of reduction. CONCLUSIONS: A short buttress plate fixation of posterior column through single ilioinguinal approach for complex acetabular fractures is a safe and effective method. PMID- 27198872 TI - From the Editors. PMID- 27198870 TI - Comparison of transforaminal verse interlaminar epidural steroid injection in low back pain with lumbosacral radicular pain: a meta-analysis of the literature. AB - OBJECTIVE: The object of the present meta-analysis is to compare the effectiveness of transforaminal epidural steroid injection (TFESI) and interlaminar epidural steroid injection (ILESI) for treating patients with low back pain (LBP) secondary to lumbosacral radicular pain. METHODS: A systematic search was performed in the PubMed and Embase databases and the Cochrane Library for relevant literature published through January 2016. The randomized controlled trials (RCTs) and controlled observational studies were selected, which did not only compare TFESI with ILESI but also reported the available data. The Cochrane Collaboration's Handbook and Newcastle-Ottawa Scale (NOS) were used for the methodological quality assessments of the RCTs and observational studies respectively. The meta-analysis was performed using the Revman 5.2 software. RESULTS: A total of 931 patients from nine RCTs and four observational studies were subjected to meta-analysis. In primary outcomes, the TFESI patients experienced superior pain relief compared with the TFESI patients in RCTs (P = 0.01), but not in observational studies (p = 0.63). The pooled data of RCTs showed that the TFESI group presented superior clinical results in terms of visual analogue scale (VAS) than the ILESI group (p = 0.0005). Moreover, the numeric rating scale (NRS) specifically favored TFESI in the RCTs (p < 0000.1). Similar functional improvement and oswentry disability index (ODI) score were observed between TFESI and ILESI in RCTs (P = 0.62). In secondary outcomes, meta analysis of RCTs and observational studies revealed that there were no statistically significant differences between both groups in regard to procedure frequency, surgery rate, and ventral epidural spread. CONCLUSIONS: According to the results of meta-analysis, TFESI to manage LBP provides superior short term pain relief and equal functional improvement when compared to ILESI. It has not shown a statistically significant difference between both groups with regard to procedure frequency, surgery rate, and ventral epidural spread. PMID- 27198873 TI - Advancing Methods for National and Global Risk Studies. PMID- 27198874 TI - Response. PMID- 27198875 TI - Risk Management Should Play a Stronger Role in Developing and Implementing Social Responsibility Policies for Organizations. PMID- 27198876 TI - Modeling Lung Carcinogenesis in Radon-Exposed Miner Cohorts: Accounting for Missing Information on Smoking. AB - Epidemiological miner cohort data used to estimate lung cancer risks related to occupational radon exposure often lack cohort-wide information on exposure to tobacco smoke, a potential confounder and important effect modifier. We have developed a method to project data on smoking habits from a case-control study onto an entire cohort by means of a Monte Carlo resampling technique. As a proof of principle, this method is tested on a subcohort of 35,084 former uranium miners employed at the WISMUT company (Germany), with 461 lung cancer deaths in the follow-up period 1955-1998. After applying the proposed imputation technique, a biologically-based carcinogenesis model is employed to analyze the cohort's lung cancer mortality data. A sensitivity analysis based on a set of 200 independent projections with subsequent model analyses yields narrow distributions of the free model parameters, indicating that parameter values are relatively stable and independent of individual projections. This technique thus offers a possibility to account for unknown smoking habits, enabling us to unravel risks related to radon, to smoking, and to the combination of both. PMID- 27198877 TI - Does Electrode Design Matter in Ablation Effect Assessments? PMID- 27198878 TI - Parametric analysis of RNA-seq expression data. AB - Various methods had been introduced for normalization and comparison of RNA-seq count data. However, they lacked objectivity because they based on ad hoc assumptions that were never verified their appropriateness. Here, we introduced a method that assumes parsimony models on data distribution; the assumptions were verified according to exploratory data analysis. As was expected, count data were lognormally distributed. The level of noise in recent data appeared to be much higher than those of microarrays. Still, the appropriate distribution model would improve certainty and accuracy of normalization, by finding out the reliable range of data. Primary cause of noise was not the principle of the methodology; that is, each read is a trial that which transcript is read. Rather, the cause would be overlooking of transcripts, and the overlooking occurred more often among lower range of data. To find out genes likely to be overlooked, number of replications would be more important than read depth, which will not prevent overlooking. Both signal and noise in the reliable range of data were distributed normally, showing the suitability to use generalized linear model to evaluate differences in expression levels. In the framework, normalized data can be compared and combined freely beyond studies. PMID- 27198880 TI - Royal colleges welcome junior contract agreement. PMID- 27198879 TI - Food-grade Pickering emulsions stabilised with solid lipid particles. AB - Aqueous dispersions of tripalmitin particles (with a minimum size of 130 nm) were produced, via a hot sonication method, with and without the addition of food grade emulsifiers. Depending on their relative size and chemistry, the emulsifiers altered the properties of the fat particles (e.g. crystal form, dispersion state and surface properties) by two proposed mechanisms. Firstly, emulsifiers modify the rate and/or extent of polymorphic transitions, resulting in the formation of fat crystals with a range of polarities. Secondly, the adsorption of emulsifiers at the particle interface modifies crystal surface properties. Such emulsifier-modified fat particles were then used to stabilise emulsions. As the behaviour of these particles was predisposed by the kind of emulsifier employed for their manufacture, the resulting particles showed different preferences to which of the emulsion phases (oil or water) became the continuous one. The polarity of the fat particles decreased as follows: Whey Protein Isolate > Soy Lecithin > Soy Lecithin + Tween 20 > Tween 20 > Polyglycerol Polyricinoleate > no emulsifier. Consequently, particles stabilised with WPI formed oil-in-water emulsions (O/W); particles stabilised solely with lecithin produced a highly unstable W/O emulsion; and particles stabilised with a mixture of lecithin and Tween 20 gave a stable W/O emulsion with drop size up to 30 MUm. Coalescence stable, oil-continuous emulsions (W/O) with drop sizes between 5 and 15 MUm were produced when the tripalmitin particles were stabilised with solely with Tween 20, solely with polyglycerol polyricinoleate, or with no emulsifier at all. It is proposed that the stability of the latter three emulsions was additionally enhanced by sintering of fat particles at the oil water interface, providing a mechanical barrier against coalescence. PMID- 27198882 TI - [Let's also check if clinical practice guidelines are correctly used and if they do work. Authors reply]. PMID- 27198881 TI - Survey of the genome of Pogostemon cablin provides insights into its evolutionary history and sesquiterpenoid biosynthesis. AB - Pogostemon cablin (Blanco) Benth. (Patchouli) is an important traditional Chinese medicinal plant that has both essential oil value and a broad range of therapeutic effects. Here we report the first de novo assembled 1.15-Gb draft genome sequence for P. cablin from next-generation sequencing technology. Our assembly, with a misassembly rate of <4 bp per 100 kb, is ~73% of the predicted genome size (1.57 Gb). Analysis of whole-genome sequences identified 3,147,333 heterozygous single-nucleotide polymorphisms and 490,407 insertions and deletions, giving an estimated heterozygosity rate of 0.274%. A comprehensive annotation pipeline indicated that repetitive sequences make up 58.55% of the assemblies, and that there are estimated 45,020 genes. Comparative genomics analysis showed that the Phrymaceae and Lamiaceae family split ~62.80 Mya, and the divergence between patchouli and sesame occurred ~52.42 Mya, implying a potentially shared recent whole-genome duplication event. Analysis of gene homologs involved in sesquiterpenoid biosynthesis showed that patchouli contains key genes involved in more sesquiterpenoid types and has more copies of genes for each sesquiterpenoid type than several other related plant species. The patchouli genome will facilitate future research on secondary metabolic pathways and their regulation as well as potential selective breeding of patchouli. PMID- 27198884 TI - [Difficulty in surrogate decision making in spinal muscular atrophy type 1]. PMID- 27198883 TI - [Renal scarring in children under 36 months hospitalised for acute pyelonephritis]. AB - INTRODUCTION: Acute pyelonephritis (APN) is one of the most common causes of serious bacterial infection in infants. Renal scarring is the most prevalent long term complication. OBJECTIVES: To review the incidence of renal scarring within 6 months after an episode of APN in children under 36 months and its relationship with imaging studies, clinical settings, and bacteriology. METHOD: A retrospective study of previously healthy patients aged one to 36 months, admitted for a first episode of APN, with a minimum follow-up of 6 months. Demographic and clinical variables were collected along with bacteriology, renal and bladder ultrasound scan, voiding cystourethrography, DMSA-scintigraphy, and re-infection events. RESULTS: A total of 125 patients were included in the study, of which 60% were male, the large majority (92%) febrile, and due to E. coli (74.6%). There was a history of prenatal ultrasound scan changes in 15.4%. Ultrasound scan found dilation of the urinary tract in 22.1%. Voiding cystourethrography was performed on 70 patients: 54.3% no abnormalities, 12.8% vesicoureteral reflux (VUR) grade i-iii, and 32.9% iv-v grade VUR. Six patients had iv-v grade VUR with a normal ultrasound scan. Adherence to DMSA-scintigraphy at 6 months was only 61% of that indicated. Renal scarring was found in 44.3% of those in which it was performed (60 cases). CONCLUSIONS: Almost half (44%) DMSA scintigraphy in children aged one to 36 months hospitalised for APN show renal scarring at 6 months, which was found to be associated with the re-infection events and the iv-v grade VUR. There was no relationship between scarring and the bacteriology or the elevations of inflammatory biochemical markers. PMID- 27198885 TI - Routine sampling of internal mammary lymph nodes during microsurgical breast reconstruction-Experience based on 524 microsurgical breast reconstructions. AB - PURPOSE: Exploration of the internal mammary vessels during microsurgical reconstruction presents an ideal opportunity for identifying and sampling the internal mammary lymph node (IMLN) basin. METHODS: A retrospective review of patients undergoing microsurgical breast reconstruction using the internal mammary vessels as recipient vessels was conducted from March 2000 to December 2014. Patient demographics, tumor characteristics, preoperative lymph node mapping, reconstructive timing, and outcomes were studied. RESULTS: A total of 524 microsurgical breast reconstructions in 516 patients were performed using the internal mammary vessels. IMLNs were sampled in 53 immediate and 42 delayed breast reconstructions. Eight (seven in the immediate and one in the delayed group) of the sampled nodes were positive for cancer metastasis, for an incidence of 8.4% in identified lymph nodes. All patients with metastatic IMLNs subsequently received local-regional radiation and chemotherapy. All patients were alive, and six were disease-free at the conclusion of the study period, which had an average follow up of 67.3 months. CONCLUSION: Incidentally encountered IMLNs during microsurgical breast reconstruction are frequently positive. With negligible downside and the possibility to provide additional information for treatment, the procedure should be encouraged. J. Surg. Oncol. 2016;114:133-139. (c) 2016 Wiley Periodicals, Inc. PMID- 27198886 TI - Treatment with botulinum toxin in children with cerebral palsy: a qualitative study of parents' experiences. AB - BACKGROUND: In children with cerebral palsy everyday movements such as walking, standing and using one's hands can be difficult to perform because of spasticity. Botulinum neurotoxin type A (BoNT-A) are often used to reduce spasticity. The aim of this study was to describe how parents of children with cerebral palsy experienced the child's treatment with BoNT-A, how the child was affected by the treatment and how spasticity affected the child. METHODS: A qualitative study in which 15 parents of children (6-13 years old) with cerebral palsy were interviewed about their experiences of the BoNT-A treatment. The children had received several BoNT-A treatments. An interview guide was used with topics: the child's functions before and after the treatment, the outcomes of the treatment and how they valued the BoNT-A treatment. Content analysis was used to analyse the interviews. RESULTS: The analyses resulted in two themes: 'When softness comes and goes' and 'Both want and do not want'. The reduction of spasticity - softness - was described to promote motor functions, and facilitate the next step in motor development. The children were described as being more active out of their own initiative and having a happier mood. Spasticity, described as stiffness, was described to make walking more strenuous as well as interfering with activities. The BoNT-A injection procedure was perceived as troublesome and painful for the child, and sometimes traumatic for both children and parents. CONCLUSIONS: Treatment with BoNT-A was described as facilitating motor development and activity. The children's and the parents' negative experiences of the injection procedure should be addressed. PMID- 27198887 TI - Implementation of dispersion-free slow acoustic wave propagation and phase engineering with helical-structured metamaterials. AB - The ability to slow down wave propagation in materials has attracted significant research interest. A successful solution will give rise to manageable enhanced wave-matter interaction, freewheeling phase engineering and spatial compression of wave signals. The existing methods are typically associated with constructing dispersive materials or structures with local resonators, thus resulting in unavoidable distortion of waveforms. Here we show that, with helical-structured acoustic metamaterials, it is now possible to implement dispersion-free sound deceleration. The helical-structured metamaterials present a non-dispersive high effective refractive index that is tunable through adjusting the helicity of structures, while the wavefront revolution plays a dominant role in reducing the group velocity. Finally, we numerically and experimentally demonstrate that the helical-structured metamaterials with designed inhomogeneous unit cells can turn a normally incident plane wave into a self-accelerating beam on the prescribed parabolic trajectory. The helical-structured metamaterials will have profound impact to applications in explorations of slow wave physics. PMID- 27198888 TI - The DEAD-box RNA helicase 51 controls non-small cell lung cancer proliferation by regulating cell cycle progression via multiple pathways. AB - The genetic regulation of cell cycle progression and cell proliferation plays a role in the growth of non-small cell lung cancer (NSCLC), one of the most common causes of cancer-related mortality. Although DEAD-box RNA helicases are known to play a role in cancer development, including lung cancer, the potential involvement of the novel family member DDX51 has not yet been investigated. In the current study we assessed the role of DDX51 in NSCLC using a siRNA-based approach. DDX51 siRNA-expressing cells exhibited a slower cell proliferation rate and underwent arrest in S-phase of the cell cycle compared with control cells. Microarray analyses revealed that DDX51siRNA expression resulted in the dysregulation of a number of cell signalling pathways. Moreover, injection of DDX51 siRNA into an animal model resulted in the formation of smaller tumours compared with the control group. We also assessed the expression of DDX51 in patients with NSCLC, and the data revealed that the expression was correlated with patient age but no other risk factors. Overall, our data suggest for the first time that DDX51 aids cell cancer proliferation by regulating multiple signalling pathways, and that this protein might be a therapeutic target for NSCLC. PMID- 27198889 TI - High seeding density of human chondrocytes in agarose produces tissue-engineered cartilage approaching native mechanical and biochemical properties. AB - Animal cells have served as highly controllable model systems for furthering cartilage tissue engineering practices in pursuit of treating osteoarthritis. Although successful strategies for animal cells must ultimately be adapted to human cells to be clinically relevant, human chondrocytes are rarely employed in such studies. In this study, we evaluated the applicability of culture techniques established for juvenile bovine and adult canine chondrocytes to human chondrocytes obtained from fresh or expired osteochondral allografts. Human chondrocytes were expanded and encapsulated in 2% agarose scaffolds measuring ?3 4mm*2.3mm, with cell seeding densities ranging from 15 to 90*10(6)cells/mL. Subsets of constructs were subjected to transient or sustained TGF-beta treatment, or provided channels to enhance nutrient transport. Human cartilaginous constructs physically resembled native human cartilage, and reached compressive Young's moduli of up to ~250kPa (corresponding to the low end of ranges reported for native knee cartilage), dynamic moduli of ~950kPa (0.01Hz), and contained 5.7% wet weight (%/ww) of glycosaminoglycans (>= native levels) and 1.5%/ww collagen. We found that the initial seeding density had pronounced effects on tissue outcomes, with high cell seeding densities significantly increasing nearly all measured properties. Transient TGF-beta treatment was ineffective for adult human cells, and tissue construct properties plateaued or declined beyond 28 days of culture. Finally, nutrient channels improved construct mechanical properties, presumably due to enhanced rates of mass transport. These results demonstrate that our previously established culture system can be successfully translated to human chondrocytes. PMID- 27198890 TI - Quantifying thumb opposition kinematics using dynamic computed tomography. AB - Current motion capture techniques all have shortcomings when applied to the 3D quantitative evaluation of thumb base motion. Dynamic CT might overcome these shortcomings but, so far, robustness of this technique in more than one specimen has not yet been demonstrated. The aim of the current study is to further evaluate the use of dynamic CT for quantification of thumb motion in a larger cadaveric study using a protocol which is feasible in a clinical context. A dynamic CT scan was acquired from six cadaveric human forearms, while a motion simulator imposed thumb opposition. After image acquisition and segmentation, carpal bone motion was quantified using helical axes. To enable comparisons between specimens, intersection points of the instantaneous helical axis with an anatomically defined plane were determined. Precision of the dynamic CT method, measured as variation in distances between silicon nitride beads between frames of a dynamic scan, was 0.43mm (+/-0.09mm) when fixed to the skin and 0.13mm (+/ 0.04mm) when embedded into the bone. Absolute deviation between known and measured distances were not larger than 0.34mm. We could demonstrate and quantify that thumb opposition is associated with motion at the trapeziometacarpal and scaphotrapezotrapezoidal joints. High consistency in motion patterns between specimen were found, while the radiation dose was limited. We conclude that dynamic CT can be used to visualize and quantify 3D thumb kinematics, making it a promising method to explore kinematics in vivo. PMID- 27198891 TI - Clinical, angiographic and procedural characteristics of longitudinal stent deformation. AB - Recently, longitudinal stent deformation (LSD) has been reported increasingly. Even though the reported cases included almost all stent designs, most cases were seen in the ElementTM stent design (Boston Scientific, Natick, MA, USA). It is considered that stent design, lesion and procedural characteristics play a role in the etiology of LSD. Yet, the effect of LSD on long-term clinical outcomes has not been studied well. Element stents implanted between January 2013 and April 2015 in our hospital were examined retrospectively. Patients were grouped into two according to the presence of LSD, and their clinical, lesion and procedural characteristics were studied. Twenty-four LSD's were detected in 1812 Element stents deployed in 1314 patients (1.83 % of PCI cases and 1.32 % of all Element stents). LMCA lesions (16.7 % vs 1.6 %, p < 0.001), complex lesions (75 % vs 35.1 %, p < 0.001), bifurcation lesions (37.5 % vs 18.3 %, p = 0.017), ostial lesions (33.3 % vs 12.8 %, p = 0.003), using of extra-support guiding catheter (54.2 % vs 22.3 %, p < 0.001) and extra-support guidewire (37.5 % vs 16.2 %, p = 0.005) were found to be more frequent in cases with LSD than in cases without it. In addition, the number of stents, stent inflation pressure and the use of post dilatation were significantly different between the two groups. Two patients had an adverse event during the follow-up period. LSD is a rarely encountered complication, and is more common in complex lesions such as ostial, bifurcation and LMCA lesions. The use of extra-support guiding catheter, extra-support guidewires and low stent inflation pressure increases the occurrence of LSD. Nevertheless, with increased awareness of LSD and proper treatment, unwanted long term outcomes can be successfully prevented. PMID- 27198892 TI - Quantitative diffusion-weighted magnetic resonance imaging in the assessment of myocardial fibrosis in hypertrophic cardiomyopathy compared with T1 mapping. AB - To identify myocardial fibrosis in hypertrophic cardiomyopathy (HCM) subjects using quantitative cardiac diffusion-weighted imaging (DWI) and to compare its performance with native T1 mapping and extracellular volume (ECV). Thirty-eight HCM subjects (mean age, 53 +/- 9 years) and 14 normal controls (mean age, 51 +/- 8 years) underwent cardiac magnetic resonance imaging (CMRI) on a 3.0T magnetic resonance (MR) machine with DWI, T1 mapping and late gadolinium enhancement (LGE) imaging as the reference standard. The mean apparent diffusion coefficient (ADC), native T1 value and ECV were determined for each subject. Overall, the HCM subjects exhibited an increased native T1 value (1241.04 +/- 78.50 ms), ECV (0.31 +/- 0.03) and ADC (2.36 +/- 0.34 s/mm(2)) compared with the normal controls (1114.60 +/- 37.99 ms, 0.24 +/- 0.04, and 1.62 +/- 0.38 s/mm(2), respectively) (p < 0.05). DWI differentiated healthy and fibrotic myocardia with an area under the curve (AUC) of 0.93, while the AUCs of the native T1 values (0.93), (p > 0.05) and ECV (0.94), (p > 0.05) exhibited an equal differentiation ability. Both HCM LGE+ and HCM LGE- subjects had an increased native T1 value, ECV and ADC compared to the normal controls (p < 0.05). HCM LGE+ subjects exhibited an increased ECV (0.31 +/- 0.04) and ADC (2.43 +/- 0.36 s/mm(2)) compared to HCM LGE- subjects (p < 0.05). HCM LGE+ and HCM LGE- subjects had similar native T1 values (1250 +/- 76.36 ms vs. 1213.98 +/- 92.30 ms, respectively) (p > 0.05). ADC values were linearly associated with increased ECV (R(2) = 0.36) and native T1 values (R(2) = 0.40) among all subjects. DWI is a feasible alternative to native T1 mapping and ECV for the identification of myocardial fibrosis in patients with HCM. DWI and ECV can quantitatively characterize the extent of fibrosis in HCM LGE+ and HCM LGE- patients. PMID- 27198894 TI - Erratum: Respiratory Motor Function in Individuals with Centronuclear Myopathies. PMID- 27198895 TI - Erratum: Reply: Respiratory motor function in centronuclear myopathy. PMID- 27198893 TI - Transcriptome shock invokes disruption of parental expression-conserved genes in tetraploid wheat. AB - Allopolyploidy often triggers phenotypic novelty and gene expression remolding in the resulting polyploids. In this study, we employed multiple phenotypic and genetic approaches to investigate the nature and consequences of allotetraploidization between A- and S-subgenome of tetraploid wheat. Results showed that karyotype of the nascent allopolyploid plants (AT2) is stable but they showed clear novelty in multiple morphological traits which might have positively contributed to the initial establishment of the tetraploids. Further microarray-based transcriptome profiling and gene-specific cDNA-pyrosequencing have documented that transcriptome shock was exceptionally strong in AT2, but a substantial proportion of the induced expression changes was rapidly stabilized in early generations. Meanwhile, both additive and nonadditive expression genes showed extensive homeolog expression remodeling and which have led to the subgenome expression dominance in leaf and young inflorescence of AT2. Through comparing the homeolog-expressing patterns between synthetic and natural tetraploid wheats, it appears that the shock-induced expression changes at both the total expression level and subgenome homeolog partitioning are evolutionarily persistent. Together, our study shed new light on how gene expression changes have rapidly occurred at the initial stage following allotetraploidization, as well as their evolutionary relevance, which may have implications for wheat improvements. PMID- 27198896 TI - Repair of large osteochondritis dissecans lesions using a novel multilayered tissue engineered construct in an equine athlete. AB - Osteochondral lesions resulting from osteochondritis dissecans are problematic to treat and present a significant challenge for clinicians. The aims of this study were to investigate the use of a scaffold-assisted microfracture approach, employing a novel, multilayered, collagen-based, osteochondral graft substitute in the treatment of severe osteochondritis dissecans of both lateral femoral trochlear ridges in an equine athlete, and to assess the potential of this novel scaffold to enhance repair of the osteochondral unit. A 15 month-old female filly presented with large osteochondritis dissecans lesions involving both femoral lateral trochlear ridges. After routine arthroscopic debridement and microfracture of the subchondral bone, multilayered osteochondral defect repair scaffolds were implanted into the fragmentation beds in both left and right femoropatellar joints via mini-arthrotomies. Exploratory arthroscopy 5 months postimplantation revealed smooth cartilaginous repair tissue, contiguous with the adjacent cartilage, covering the defect. At 22-month follow up, the filly had no signs of lameness and was exercising at her intended level. Radiographically, although still slightly flattened, the femoral trochlear ridges were smooth, with no evidence of osteoarthritis. Ultrasonographically, the defects were filled with bone and covered with an overlying cartilaginous layer, with the trochlear ridge contour almost entirely restored. This report demonstrates the effective clinical use of this novel, multilayered, osteochondral defect repair scaffold in the treatment of osteochondritis dissecans of an equine athlete. The successful repair achieved here using this novel scaffold in an equine patient with large bilateral lesions shows the potential for clinical translation in the treatment of human patients presenting with osteochondral defects. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27198898 TI - Safe sleep, day and night: mothers' experiences regarding infant sleep safety. AB - AIMS AND OBJECTIVES: To explore Canadian mothers' experiences with infant sleep safety. BACKGROUND: Parents decide when, how and where to place their infants to sleep. It is anticipated that they will follow international Sudden Infant Death Syndrome prevention sleep safety guidelines. Limited evidence is available for how parents take up guidelines; no studies have explored Canadian mothers' experiences regarding infant sleep safety. DESIGN: An inductive qualitative descriptive study using some elements of grounded theory, including concurrent data collection and analysis and memoing. METHODS: Semi-structured interviews and constant comparative analysis were employed to explore infant sleep safety experiences of 14 Canadian mothers residing in Metro Vancouver. Data collection commenced in December 2012 and ended in July 2013. FINDINGS: The core theme, Infant Sleep Safety Cycle, represents a cyclical process encompassing sleep safety from the prenatal period to the first six months of infants' lives. The cyclical process includes five segments: mothers' expectations of sleep safety, their struggles with reality as opposed to maternal visions, modifications of expectations, provision of rationale for choices and shifts in mothers' views of infants' developmental capabilities. Mothers' experiences were influenced by four factors: perceptions of everyone's needs, familial influences, attitudes and judgments from outsiders and resource availability and accessibility. CONCLUSION: To manage infants' sleep, mothers reframed sleep safety guidelines and downplayed the risk of Sudden Infant Death Syndrome for all forms of sleep at all times. Healthcare providers can support mothers' efforts to manage their infants' sleep challenges. During prenatal and postpartum periods, providers' interventions can influence mothers' efforts to adhere to sleep safety principles. RELEVANCE TO CLINICAL PRACTICE: The study findings support healthcare providers' efforts to assist mothers to modify expectations and develop strategies to support sleep safety principles while acknowledging their challenges. PMID- 27198899 TI - Electroluminescent Materials Can Further Enhance the Nighttime Conspicuity of Pedestrians Wearing Retroreflective Materials. AB - OBJECTIVE: We investigated the nighttime conspicuity benefits of adding electroluminescent (EL) panels to pedestrian clothing that contains retroreflective elements. BACKGROUND: Researchers have repeatedly documented that pedestrians are too often not sufficiently conspicuous to drivers at night and that retroreflective materials can enhance the conspicuity of pedestrians. However, because retroreflective elements in clothing are effective only when they are illuminated by the headlamps of an approaching driver, they are not useful for pedestrians who are positioned outside the beam pattern of an approaching vehicle's headlamps. Electroluminescent materials-flexible luminous panels that can be attached to clothing-have the potential to be well suited for these conditions. METHOD: Using an open-road course at night, we compared the distances at which observers responded to pedestrians who were positioned at one of three lateral positions (relative to the vehicle's path) wearing one of two high-visibility garments. RESULTS: The garment that included both EL and retroreflective materials yielded longer response distances than the retroreflective-only garment. This effect was particularly strong when the test pedestrian was positioned farthest outside of the area illuminated by headlamps. CONCLUSION: These findings suggest that EL materials can further enhance the conspicuity of pedestrians who are wearing retroreflective materials. APPLICATION: EL materials can be applied to garments. They may be especially valuable to enhance the conspicuity of roadway workers, emergency responders, and traffic control officers. PMID- 27198897 TI - Preclinical to Clinical Translation of Antibody-Drug Conjugates Using PK/PD Modeling: a Retrospective Analysis of Inotuzumab Ozogamicin. AB - A mechanism-based pharmacokinetic/pharmacodynamic (PK/PD) model was used for preclinical to clinical translation of inotuzumab ozogamicin, a CD22-targeting antibody-drug conjugate (ADC) for B cell malignancies including non-Hodgkin's lymphoma (NHL) and acute lymphocytic leukemia (ALL). Preclinical data was integrated in a PK/PD model which included (1) a plasma PK model characterizing disposition and clearance of inotuzumab ozogamicin and its released payload N-Ac gamma-calicheamicin DMH, (2) a tumor disposition model describing ADC diffusion into the tumor extracellular environment, (3) a cellular model describing inotuzumab ozogamicin binding to CD22, internalization, intracellular N-Ac-gamma calicheamicin DMH release, binding to DNA, or efflux from the tumor cell, and (4) tumor growth and inhibition in mouse xenograft models. The preclinical model was translated to the clinic by incorporating human PK for inotuzumab ozogamicin and clinically relevant tumor volumes, tumor growth rates, and values for CD22 expression in the relevant patient populations. The resulting stochastic models predicted progression-free survival (PFS) rates for inotuzumab ozogamicin in patients comparable to the observed clinical results. The model suggested that a fractionated dosing regimen is superior to a conventional dosing regimen for ALL but not for NHL. Simulations indicated that tumor growth is a highly sensitive parameter and predictive of successful outcome. Inotuzumab ozogamicin PK and N-Ac gamma-calicheamicin DMH efflux are also sensitive parameters and would be considered more useful predictors of outcome than CD22 receptor expression. In summary, a multiscale, mechanism-based model has been developed for inotuzumab ozogamicin, which can integrate preclinical biomeasures and PK/PD data to predict clinical response. PMID- 27198900 TI - Effects of Epinephrine Auto-Injector Shape and Size on Human Factors Influencing Drug Delivery. AB - OBJECTIVE: The aim of this study was to assess the effects of (a) auto-injector form factor on maximum applied force capability and (b) auto-injector design and instructions on force production and orientation. BACKGROUND: Effective delivery of epinephrine through an auto-injector is the result of a multitude of design factors. At minimum, the design needs to allow the user to apply sufficient force for the needle to penetrate clothing and tissue. METHOD: Trainer devices for three commercially available epinephrine auto-injectors with different form factors (cylindrical, elliptical, prismatic) were tested in a laboratory-based repeated-measures experiment with 20 adults. Participants applied their maximum force onto a force plate positioned over their thigh and practiced an injection using the trainer device after viewing training videos. Participants also rated force confidence and preference. RESULTS: The maximum force varied significantly across devices. The greatest force observed was 64 newtons with the elliptical device, and the lowest force was 61 newtons with the cylindrical device. Participants reported the highest force confidence when using the elliptical and cylindrical devices, ranking the elliptical as their preferred device. CONCLUSION: Force capability results for the elliptical device suggest that it may be more successful in achieving the necessary force for drug delivery in a larger set of adult users. APPLICATION: Results suggest that the auto-injector with the elliptical form may enable more successful drug delivery among a larger set of users. PMID- 27198901 TI - Zinc Deficiency in Childhood and Pregnancy: Evidence for Intervention Effects and Program Responses. AB - Zinc is a key micronutrient of particular importance during childhood and pregnancy. Zinc deficiency has been linked to increased infection and stunting among children and is a risk factor for adverse pregnancy outcomes and preterm delivery. Targeted interventions have the potential to alleviate the adverse effects of zinc deficiency via therapeutic and preventive supplementation, fortification and biofortification, but implementation is challenging. A growing number of low- and middle- income countries have introduced national policies for zinc treatment of diarrhea among children under 5 years in response to mounting evidence of reduced episode duration and severity as well as reduced incidence in the ensuing months, but coverage remains low in the absence of effective scale-up efforts. Implementation of preventive zinc supplementation in young children has also been slow, despite evidence linking routine daily supplementation and treatment regimens with reductions in stunting and the incidence of diarrhea and pneumonia. Acceptance of other zinc interventions, including traditional fortification, fortification with micronutrient powders and biofortification, is hindered by unclear evidence on efficacy. Additional research is therefore warranted to ascertain the efficacy of delivering zinc through fortified and biofortified foods and in combination with other micronutrients in supplements or powders. Operations research is also necessary to establish best practices for scale-up of therapeutic zinc supplementation for diarrhea. PMID- 27198902 TI - Are paramedics prepared to perform needle cricothyroidotomy? PMID- 27198903 TI - Potassium as a potential predictive biomarker of brain hypoxia in avalanche victims: preanalytical recommendations. PMID- 27198904 TI - Trends in bicycle crashes in California. PMID- 27198905 TI - Blood potassium after avalanche-induced cardiac arrest: sampling method and interpretation. PMID- 27198906 TI - Relational Resilience in Maori, Pacific, and European Sole Parent Families: From Theory and Research to Social Policy. AB - This study reports findings and policy recommendations from a research project that applied a relational resilience framework to a study of 60 sole parent families in New Zealand, with approximately equal numbers of Maori, Pacific, and European (White) participants. The sole parent families involved were already known to be resilient and the study focused on identifying the relationships and strategies underlying the achievement and maintenance of their resilience. The study was carried out to provide an evidence base for the development and implementation of policies and interventions to both support sole parent families who have achieved resilience and assist those who struggle to do so. The three populations shared many similarities in their pathways to becoming sole parents and the challenges they faced as sole parents. The coping strategies underlying their demonstrated resilience were also broadly similar, but the ways in which they were carried out did vary in a manner that particularly reflected cultural practices in terms of their reliance upon extended family-based support or support from outside the family. The commonalities support the appropriateness of the common conceptual framework used, whereas the differences underline the importance of developing nuanced policy responses that take into account cultural differences between the various populations to which policy initiatives are directed. PMID- 27198907 TI - Multisensory effects on somatosensation: a trimodal visuo-vestibular-tactile interaction. AB - Vestibular information about self-motion is combined with other sensory signals. Previous research described both visuo-vestibular and vestibular-tactile bilateral interactions, but the simultaneous interaction between all three sensory modalities has not been explored. Here we exploit a previously reported visuo-vestibular integration to investigate multisensory effects on tactile sensitivity in humans. Tactile sensitivity was measured during passive whole body rotations alone or in conjunction with optic flow, creating either purely vestibular or visuo-vestibular sensations of self-motion. Our results demonstrate that tactile sensitivity is modulated by perceived self-motion, as provided by a combined visuo-vestibular percept, and not by the visual and vestibular cues independently. We propose a hierarchical multisensory interaction that underpins somatosensory modulation: visual and vestibular cues are first combined to produce a multisensory self-motion percept. Somatosensory processing is then enhanced according to the degree of perceived self-motion. PMID- 27198908 TI - Acetophenone azine: a new allergen responsible for severe contact dermatitis from shin pads. AB - BACKGROUND: Contact dermatitis resulting from the use of shin pads is usually caused by rubber components, dyes, benzoyl peroxide, or formaldehyde resins. OBJECTIVES: To investigate and identify a new allergen in shin pads that was responsible for severe contact dermatitis in a young football player. METHODS: High-performance liquid chromatography (HPLC) of samples of shin pads was performed. The boy was patch tested with pieces of shin pads and with acetophenone azine, a chemical substance identified by HPLC in the foam of the shin pads. RESULTS: HPLC identified acetophenone azine at concentrations of approximately 20 ug/g of shin pad samples. Patch tests gave strongly positive reactions to pieces of shin pads and to acetophenone azine down to 0.001% in acetone, whereas acetophenone and hydrazine sulfate were both negative. Twenty controls were negative for acetophenone azine 0.01% in acetone. CONCLUSIONS: Acetophenone azine is a new, strong allergen of shin pads, and more generally of other sport equipment based on ethylene vinyl acetate. It may be used as a biocide, but this has to be confirmed. Further investigations are needed to understand factors such as exposure, cross-reaction patterns, metabolism, and the optimal patch test preparation. PMID- 27198909 TI - Challenging 'girls only' publicly funded human papillomavirus vaccination programmes. AB - This analysis examines the 'girls only' policy for publicly funded human papillomavirus (HPV) vaccination programmes. Current funding policy in most Canadian provinces covers 'girls only' with the goal of reducing mortality and morbidity rates of HPV-related cervical cancer. Recent studies indicate increasing rates of other HPV-related cancers among cisgender men and women. The HPV vaccine is proving effective against some of these cancers. Statistics on HPV vaccine uptake among individuals with different gender expressions are scarce. Critics argue that a 'girls only' HPV vaccine policy is inequitable. We add to this critique by reflecting on the gender binary embedded in such policies and produced through epidemiological studies that attend differentially to females, reinforcing exclusionary practices that leave out those who form their gender identities across the spectrum. We then draw on deontological (duties-based) and utilitarian (utility-based) frameworks to show that these gendered policies are also unethical. These challenges to the assumptions underlying 'girls only' immunization programmes have implications for nurses and the healthcare system. If we are to advance equitable and ethical health outcomes, we entreat nurses as a collective to mobilize the public to lobby federal, provincial and territorial governments to fund more inclusive HPV vaccination policies. PMID- 27198910 TI - Examining the Contributions of Image-Charge Forces to Charge Reversal: Discrete Versus Continuum Modeling of Surface Charges. AB - The effects of both repulsive and attractive image-charge forces on the structure of electric double layers are addressed by Monte Carlo determination, based on a primitive model of electrolytes in contact with two types of identically charged surfaces: one with a homogeneously smeared-out charge density and the other with discrete interfacial groups. It is shown that the behavior of ions is closely related to surface charge distributions. Moreover, charge reversal in the absence of image charges witnesses an initial enhancement and then follows a fast suppression with increasing valence of the interfacial groups. The situation is quite similar to what are observed in the presence of repulsive image charges, which can significantly facilitate counterion condensation by overcoming the electrostatic barrier presented by the low dielectric substrate. With transition to attractive image-charge interactions, however, charge reversal remains widely unaffected in different surface charge representations, which even becomes much weaker when compared to the corresponding cases of both no images and repulsive images, provided that the interfacial groups have adequate valences. The overall scenario is found to be independent of the surface charge density values under study. These findings clearly illustrate the enormous improvement in our quantitative understanding of the electric double layer structure and the associated charge reversal phenomenon at the interface of various substrates. PMID- 27198911 TI - Multidimensional symptom clusters: an exploratory factor analysis in advanced chronic kidney disease. AB - AIMS: To explore the existence of symptom clusters in advanced chronic kidney disease. BACKGROUND: People with chronic kidney disease commonly report multiple symptoms. However, the complex relationships among these symptoms are still poorly understood. DESIGN: Cross-sectional. METHODS: A total of 436 people with stage 4 and 5 chronic kidney disease were recruited from three tertiary hospitals during 2013-2014. Participants completed the Chronic Kidney Disease-Symptom Burden Index that assesses four symptom dimensions (occurrence, distress, severity and frequency) of 32 symptoms. Exploratory factor analysis was used to identify symptom clusters across each symptom dimension. Core symptoms in each cluster were determined based on stability across dimensions and clinical plausibility. A high cutoff of 0.50 for factor loading was used for all analyses. RESULTS: Five symptom clusters were consistently identified across all symptom dimensions: fluid volume symptoms, neuromuscular symptoms, gastrointestinal symptoms, sexual symptoms and psychological symptoms. Overall, clusters ranged from 2-10 symptoms. Several symptoms were also interconnected with multiple clusters. Fatigue cross-loaded on all five clusters, whereas sleep disturbance and restless leg symptoms cross-loaded across three clusters. CONCLUSIONS: Adopting a symptom cluster approach has the potential to significantly advance symptom assessment and nursing care for people in advanced stages of chronic kidney disease. Routine clinical assessment and management strategies targeted at the cluster level should have synergistic effects in reducing symptoms. Fatigue is a pervasive symptom in advanced chronic kidney disease that is interconnected with global symptom burden, suggesting better management of symptom clusters may also reduce fatigue. PMID- 27198912 TI - SAFO: A Systematic Partnership to Reduce Vitamin A Deficiency in Tanzania. PMID- 27198913 TI - Sampling image segmentations for uncertainty quantification. AB - In this paper, we introduce a method to automatically produce plausible image segmentation samples from a single expert segmentation. A probability distribution of image segmentation boundaries is defined as a Gaussian process, which leads to segmentations which are spatially coherent and consistent with the presence of salient borders in the image. The proposed approach is computationally efficient, and generates visually plausible samples. The variability between the samples is mainly governed by a parameter which may be correlated with a simple Dice's coefficient, or easily set by the user from the definition of probable regions of interest. The method is extended to the case of several neighboring structures, but also to account for under or over segmentation, and the presence of excluded regions. We also detail a method to sample segmentations with more general non-stationary covariance functions which relies on supervoxels. Furthermore, we compare the generated segmentation samples with several manual clinical segmentations of a brain tumor. Finally, we show how this approach can have useful applications in the field of uncertainty quantification, and an illustration is provided in radiotherapy planning, where segmentation sampling is applied to both the clinical target volume and the organs at risk. PMID- 27198915 TI - Target-object integration, attention distribution, and object orientation interactively modulate object-based selection. AB - The representational basis of attentional selection can be object-based. Various studies have suggested, however, that object-based selection is less robust than spatial selection across experimental paradigms. We sought to examine the manner by which the following factors might explain this variation: Target-Object Integration (targets 'on' vs. part 'of' an object), Attention Distribution (narrow vs. wide), and Object Orientation (horizontal vs. vertical). In Experiment 1, participants discriminated between two targets presented 'on' an object in one session, or presented as a change 'of' an object in another session. There was no spatial cue-thus, attention was initially focused widely and the objects were horizontal or vertical. We found evidence of object-based selection only when targets constituted a change 'of' an object. Additionally, object orientation modulated the sign of object-based selection: We observed a same-object advantage for horizontal objects, but a same-object cost for vertical objects. In Experiment 2, an informative cue preceded a single target presented 'on' an object or as a change 'of' an object (thus, attention was initially focused narrowly). Unlike in Experiment 1, we found evidence of object-based selection independent of target-object integration. We again found that the sign of selection was modulated by the objects' orientation. This result may reflect a meridian effect, which emerged due to anisotropies in the cortical representations when attention is oriented endogenously. Experiment 3 revealed that object orientation did not modulate object-based selection when attention was oriented exogenously. Our findings suggest that target-object integration, attention distribution, and object orientation modulate object-based selection, but only in combination. PMID- 27198914 TI - Magnetic Resonance Elastography Demonstrating Low Brain Stiffness in a Patient with Low-Pressure Hydrocephalus: Case Report. AB - The authors describe the case of a 19-year-old female with shunted aqueductal stenosis who presented with low-pressure hydrocephalus that responded to negative pressure drainage. A magnetic resonance elastography scan performed 3 weeks later demonstrated very low brain tissue stiffness (high brain tissue compliance). An analysis of the importance of this finding in understanding this rare condition is discussed. PMID- 27198917 TI - Corrigendum to "Efficient detection of internal infestation in wheat based on biophotonics" [J. Photochem. Photobiol., B 155 (February 2016) 137-143]. PMID- 27198916 TI - The availability of attentional resources modulates the inhibitory strength related to weakly activated priming. AB - The current study investigated the role of attention in inhibitory processes (the inhibitory processes described in the current study refer only to those associated with masked or flanked priming) using a mixed paradigm involving the negative compatibility effect (NCE) and object-based attention. Accumulating evidence suggests that attention can be spread more easily within the same object, which increases the availability of attentional resources, than across different objects. Accordingly, we manipulated distractor location (with primes presented in the same object versus presented in different objects) together with prime/target compatibility (compatible versus incompatible) and prime-distractor stimulus onset asynchrony (SOA, 23 ms vs 70 ms). The aim was to investigate whether inhibitory processes related to weakly activated priming, which have been previously assumed to be automatic, depend on the availability of attentional resources. The results of Experiment 1 showed a significant NCE for the 70-ms SOA when the prime and distractor were presented in the same object (greater attentional resource availability); however, reversed NCEs were obtained for all other conditions. Experiment 2 was designed to disentangle whether the results of Experiment 1 were affected by the prime position, and the results indicated that the prime position did not modulate the NCE in Experiment 1. Together, these results are consistent with the claim that the availability of attentional resources modulates the inhibitory strength related to weakly activated priming. Specifically, if attentional resources are assigned to the distractor when it is presented in the same object as the prime, the strength of the inhibition elicited by the distractor may increase and reverse the activation elicited by the prime, which could lead to a significant NCE. PMID- 27198918 TI - Etchant-free graphene transfer using facile intercalation of alkanethiol self assembled molecules at graphene/metal interfaces. AB - We report a novel etchant-free transfer method of graphene using the intercalation of alkanethiol self-assembled monolayers (SAMs) at the graphene/Cu interfaces. The early stage of intercalation proceeds through graphene grain boundaries or defects within a few seconds at room temperature until stable SAMs are formed after a few hours. The formation of SAMs releases the compressive strain of graphene induced by Cu substrates and make graphene slightly n-doped due to the formation of interface dipoles of the SAMs on metal surfaces. After SAM formation, the graphene is easily delaminated off from the metal substrates and transferred onto insulating substrates. The etchant-free process enables us to decrease the density of charged impurities and the magnitude of potential fluctuation in the transferred graphene, which suppress scattering of carriers. We also demonstrate the removal of alkanethiol SAMs and reuse the substrate. This method will dramatically reduce the cost of graphene transfer, which will benefit industrial applications such as of graphene transparent electrodes. PMID- 27198919 TI - A Novel System for Single-Port Laparoscopic Surgery: Preliminary Experience. AB - AIMS: To present preliminary data of single-access laparoscopic surgery with a new device for the treatment of benign adnexal pathologies. METHODS: Ten women with benign adnexal pathologies underwent salpingectomy (n = 4) and ovarian/para ovarian cyst enucleation (n = 6) using a laparo-endoscopic single-port approach with an innovative advanced multiport reusable trocar inserted transumbilically through a small wound retractor. Trocar introduction time, operative time, estimated blood loss, conversion to standard laparoscopy, peri- and postoperative complications, hospital stay and Visual Analog Scale score (as assessment of pain and cosmesis) were analyzed. RESULTS: Port placement was successful in all patients. Mean trocar introduction time was 4.4 min (range 3.4-5.3 min) and no intra or postoperative complication occurred. The mean operating time was 50.0 +/ 9.2 min and mean blood loss was 28.5 +/- 8.8 ml. The mean hospital stay following surgery was 1.6 +/- 0.5 days and convalescence was complete in 1 week. Neither scores for postoperative incisional pain nor cosmesis side effects have been observed in any subjects. CONCLUSION: We concluded that adnexal single-port surgery performed with this innovative advanced surgical instrumentation is a feasible, safe, and effective technique that drastically reduces postoperative pain and does not compromise cosmetic appearance. The isolation of the operative field by means of the drape prevents the contamination of the port site that occurs frequently, and mainly in adnexal pathologies of uncertain etiology. In addition, the ease of insertion and the conformation of the new port access also make the procedure feasible in obese patients. PMID- 27198920 TI - Steroidal composition and cytotoxic activity from fruiting body of Cortinarius xiphidipus. AB - From the fruiting body of ectomycorrhizal fungi Cortinarius xiphidipus, sterols were identified from the crude extract and the cytotoxic effect of ergosta-4, 6, 8(14), 22-tetraen-3-one (ergone) was evaluated. Ten sterols including ergosta 3,5,7,9(11),22-pentaene, (22E)-ergosta-5,7,9(11),22-tetraen-3b-ol, (3beta,22E) ergosta-5,7,22-trien-3-ol, (22E)-ergosta-7,22-dien-3-ol, neoergosterol, (3beta) ergosta-5,8-dien-3-ol, (3beta)-ergosta-7-en-3-ol, stigmasterol, stigmasterol 22,23-dihydro and (22E)-ergosta-4,6,8(14),22-tetraen-3-one were identified from the crude extract. The cytotoxic activity of the sterol fraction containing ergosta-4, 6, 8(14), 22-tetraen-3-one was assessed on four tumour cell lines (Neuro-2a, Saos-2, MCF7 and LNCaP-C42). The cytotoxic activity against the four tumour cell lines tested, being Neuro-2a and Saos-2 the most sensitive, with a half-maximal inhibitory concentration (IC50) of 20.8 +/- 2.2 and 27.8 +/- 1.0 MUg/mL, respectively. This is the first report of this Antarctic fungi collected in the Magallanes and Chilean Antarctica Region. This work represents a potential source for the development of anticancer drugs. PMID- 27198921 TI - [Prevalence and user profile of electronic cigarettes in Spain (2014)]. AB - OBJECTIVE: To describe the prevalence and user profile of electronic cigarettes among Spanish adults and evaluate the potential dual use of these devices with combustible or conventional tobacco in 2014 in Spain. METHODS: Cross-sectional study of a representative sample of the Spanish adult (16-75 years old) population (n=1,016). A computer-assisted telephone survey was conducted in 2014. The prevalence and 95% confidence intervals (95% CI) for the use of electronic cigarettes stratified by gender, age, tobacco consumption and social status were calculated. The sample was weighted and a logistic regression model adjusted to obtain the crude odds ratios (OR) adjusted by gender, age and social status. RESULTS: 10.3% (95% CI: 8.6-12.4) of the Spanish adult population stated being ever users of electronic cigarettes (2% current users, 3.2% past users and 5.1% experimental users). Among current electronic cigarette users, 57.2% also smoked combustible or conventional tobacco, 28% had never smoked and 14.8% were former smokers. The prevalence of electronic cigarette use was higher in the younger population (adjusted OR=23.8; 95% CI: 2.5-227.7) and smokers of combustible tobacco (adjusted OR=10.1; 95% CI: 5.8-17.5). CONCLUSIONS: The use of electronic cigarettes in Spain is scarce and is most prevalent among young people and tobacco smokers. Nevertheless, one out of four current electronic cigarette users have never smoked. Hence, the regulation of these devices should be reinforced to avoid a possible gateway to nicotine products among never smokers. PMID- 27198922 TI - Meta-analysis of studies using statins as a reducer for primary liver cancer risk. AB - A protective effect of statins on primary liver cancer (PLC) risk has been suggested. However, issues about the dose-response relationship, the protective effect of individual statins, and PLC risk reduction among at-risk populations remain unsolved. Therefore, a meta-analysis was conducted. PubMed and EMBASE were searched for studies providing the risk ratio (RR) on statins and PLC risk. Summary RRs were calculated using a random-effects model. Twenty-five studies were identified. Stain use was significantly associated with a reduced risk of PLC (RR = 0.60, 95% confidence interval (CI) = 0.53-0.69). The summary RR for every additional 50 cumulative defined daily doses per year was 0.87 (95% CI = 0.83-0.91). Evidence of a non-linear dose-response relationship between statins and PLC risk was found (Pnon-linearity < 0.01). All individual statins significantly reduced PLC risk, and the risk reduction was more evident with rosuvastatin. The inverse association between statins and PLC risk remained among populations with common risk factors. Subgroup analyses revealed more significant reduction in PLC risk by statins in high- versus non-high-risk populations (Pinteraction = 0.02). Overall, these findings add to our understanding of the association between statins and PLC risk. Whether statin use is causally associated with a reduced risk of PLC should be further studied. PMID- 27198923 TI - Major cereal crops benefit from biological nitrogen fixation when inoculated with the nitrogen-fixing bacterium Pseudomonas protegens Pf-5 X940. AB - A main goal of biological nitrogen fixation research has been to expand the nitrogen-fixing ability to major cereal crops. In this work, we demonstrate the use of the efficient nitrogen-fixing rhizobacterium Pseudomonas protegens Pf-5 X940 as a chassis to engineer the transfer of nitrogen fixed by BNF to maize and wheat under non-gnotobiotic conditions. Inoculation of maize and wheat with Pf-5 X940 largely improved nitrogen content and biomass accumulation in both vegetative and reproductive tissues, and this beneficial effect was positively associated with high nitrogen fixation rates in roots. 15 N isotope dilution analysis showed that maize and wheat plants obtained substantial amounts of fixed nitrogen from the atmosphere. Pf-5 X940-GFP-tagged cells were always reisolated from the maize and wheat root surface but never from the inner root tissues. Confocal laser scanning microscopy confirmed root surface colonization of Pf-5 X940-GFP in wheat plants, and microcolonies were mostly visualized at the junctions between epidermal root cells. Genetic analysis using biofilm formation related Pseudomonas mutants confirmed the relevance of bacterial root adhesion in the increase in nitrogen content, biomass accumulation and nitrogen fixation rates in wheat roots. To our knowledge, this is the first report of robust BNF in major cereal crops. PMID- 27198924 TI - A motion algorithm to extract physical and motion parameters of mobile targets from cone-beam computed tomographic images. AB - PURPOSE: A motion algorithm has been developed to extract length, CT number level and motion amplitude of a mobile target from cone-beam CT (CBCT) images. MATERIALS AND METHODS: The algorithm uses three measurable parameters: Apparent length and blurred CT number distribution of a mobile target obtained from CBCT images to determine length, CT-number value of the stationary target, and motion amplitude. The predictions of this algorithm are tested with mobile targets having different well-known sizes that are made from tissue-equivalent gel which is inserted into a thorax phantom. The phantom moves sinusoidally in one direction to simulate respiratory motion using eight amplitudes ranging 0-20 mm. RESULTS: Using this motion algorithm, three unknown parameters are extracted that include: Length of the target, CT number level, speed or motion amplitude for the mobile targets from CBCT images. The motion algorithm solves for the three unknown parameters using measured length, CT number level and gradient for a well defined mobile target obtained from CBCT images. The motion model agrees with the measured lengths which are dependent on the target length and motion amplitude. The gradient of the CT number distribution of the mobile target is dependent on the stationary CT number level, the target length and motion amplitude. Motion frequency and phase do not affect the elongation and CT number distribution of the mobile target and could not be determined. CONCLUSION: A motion algorithm has been developed to extract three parameters that include length, CT number level and motion amplitude or speed of mobile targets directly from reconstructed CBCT images without prior knowledge of the stationary target parameters. This algorithm provides alternative to 4D-CBCT without requirement of motion tracking and sorting of the images into different breathing phases. The motion model developed here works well for tumors that have simple shapes, high contrast relative to surrounding tissues and move nearly in regular motion pattern that can be approximated with a simple sinusoidal function. This algorithm has potential applications in diagnostic CT imaging and radiotherapy in terms of motion management. PMID- 27198925 TI - Bacterial mutagenicity assays: Vehicle and positive control results from the standard Ames assay, the 6- and 24-well miniaturized plate incorporation assays and the Ames IITM assay. AB - Bacterial mutation assays are conducted routinely as part of the safety assessment of new chemicals. The OECD Test Guideline (TG) 471 describes the conduct of the standard agar plate Ames assay, required for regulatory submissions. Higher throughput non-OECD 471 TG assays, such as the miniaturized plate incorporation and Ames IITM assays, can be used for prescreening purposes. We have compiled historical vehicle and positive control data generated using these methods. The historical database is comprised from experiments spanning 9 years and includes >1000 experiments from the standard Ames assay using the plate incorporation and pre-incubation methods (TA98, TA100, TA1535, TA1537, and WP2 uvrA), >50 experiments from the 6-well (TA98, TA100, TA1535, TA97a, and WP2 uvrA) and >100 experiments from the 24-well (TA98, TA100, TA102, TA1535, TA1537, and TA97a) plate incorporation assays, and >1000 experiments from the Ames IITM assay (TA98 and TAMix). Although miniaturization to a 24-well format made the measurement of control revertant colonies in TA1537 and TA1535 more difficult; this can be overcome by using an alternative strain with a higher spontaneous reversion rate (i.e., using TA97a instead of TA1537) or by increasing the number of replicate wells to 12 (for TA1535). All three miniaturized methods, including the Ames IITM assay, were responsive to known mutagens and the responses were reproducible over years of use. These data demonstrate the excellent reproducibility of the standard and miniaturized bacterial mutation assays using positive control chemicals. Environ. Mol. Mutagen. 57:483-496, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27198926 TI - Harnessing Thin-Film Continuous-Flow Assembly Lines. AB - Inspired by nature's ability to construct complex molecules through sequential synthetic transformations, an assembly line synthesis of alpha-aminophosphonates has been developed. In this approach, simple starting materials are continuously fed through a thin-film reactor where the intermediates accrue molecular complexity as they progress through the flow system. Flow chemistry allows rapid multistep transformations to occur via reaction compartmentalization, an approach not amenable to using conventional flasks. Thin film processing can also access facile in situ solvent exchange to drive reaction efficiency, and through this method, alpha-aminophosphonate synthesis requires only 443 s residence time to produce 3.22 g h(-1) . Assembly-line synthesis allows unprecedented reaction flexibility and processing efficiency. PMID- 27198927 TI - Incident osteoarthritis associated with increased allied health services use in 'baby boomer' Australian women. AB - OBJECTIVE: To explore impact of incident osteoarthritis (OA) on health services use by Australian women born 1946-51. METHODS: Secondary analysis of Australian Longitudinal Study on Women's Health survey data linked to Medicare Australia databases (2002 to 2011). Medicare services use was compared for two groups: OA group (n=761) - reported incident OA in 2007; Never group (n=4346) - did not report arthritis in time frame. Interrupted time series regression compared health services use over time. RESULTS: The OA group had higher health services use than the Never group. Rate of services use increased over time for both groups. Rate of increase in quarterly doctor attendances was significantly lower for the OA group after onset of OA, with no corresponding change for the Never group. CONCLUSIONS: A pre-existing higher use of health services is associated with reporting incident OA, compared to those who never report arthritis. After onset of OA, rate of doctor use reduced and allied health use increased, consistent with recommended Australian treatment guidelines. IMPLICATIONS: This study provides a rare insight into change in healthcare use for people reporting incident OA, against an appropriate comparison group, highlighting the importance of early diagnosis of OA to optimise effective use of health services. PMID- 27198928 TI - Optimal clinical risk prediction can be achieved by combining quantitative fetal fibronectin and cervical length, and avoiding thresholds. PMID- 27198929 TI - Review article: long-term safety of nucleoside and nucleotide analogues in HBV monoinfected patients. AB - BACKGROUND: Nucleos(t)ide analogues (NUCs) for chronic hepatitis B treatment achieve high rates of viral suppression and are generally well tolerated. Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are the currently preferred first-line agents. The safety of these agents in clinical practice is particularly relevant since long-term treatment is usually required. AIM: To summarise and critically discuss recent real-world evidence on the safety of treatment with ETV or TDF in hepatitis B virus (HBV)-monoinfected patients. METHODS: PubMed and conference proceedings up to 15th June 2015 were searched using the terms ((((Hepatitis_B) OR HBV) AND ((tenofovir) OR entecavir)) AND (((lactic_acidosis) OR bone) OR renal)). RESULTS: In selected populations included in registration studies, both ETV and TDF were well tolerated with no clinically significant renal toxicity or lactic acidosis. Growing 'real-world' clinical experience with these agents includes some reports of ETV-associated lactic acidosis and TDF-associated renal impairment; however, evidence from cohort studies appears to be conflicting. In the case of ETV-related lactic acidosis, a small number of cases have been reported, all in patients with decompensated cirrhosis. The degree of association between TDF treatment and changes in markers of renal function varies between studies: discrepancies may result from the use of different definitions and cut-offs for reporting renal toxicities, and differences in patient populations. CONCLUSIONS: Pre-treatment and on-treatment monitoring of eGFR and phosphorus, with prompt appropriate dose adjustment or treatment switch can minimise the impact of NUC renal toxicity. Standardisation of measures of renal impairment and identification of early molecular markers remain an unmet need. PMID- 27198933 TI - ICBS and ECBS Chemical Biology Meeting 2015 - Let Them Come to Berlin! PMID- 27198934 TI - Morality is real, objective, and supernatural. AB - The goal of this paper is to briefly introduce and defend the idea that God is the source of our moral obligations. In contrast to Michael Shermer's paper, which defends a naturalistic position about the foundations of morality, this approach is explicitly supernaturalistic. The paper begins by defining how "God" will be understood, and then spells out some of the details of how, on the proposed view, moral obligations are to depend upon God. The third section briefly reviews some of the leading arguments for this view, before the paper concludes with a discussion of the Euthyphro dilemma. PMID- 27198936 TI - FRET Imaging of Enzyme-Responsive HPMA Copolymer Conjugate. AB - Fluorescence resonance energy transfer (FRET) is applied to investigate the enzyme-responsive payload release from a macromolecular therapeutic. The donor Cy5 is attached to the N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer backbone and the acceptor Cy7 is bound to the termini of enzyme-sensitive peptide side chains. Upon exposure to an enzyme, the bond between the peptide and Cy7 is cleaved, thereby leading to the loss of FRET signal. This enzyme response is visualized at the cell, tissue and whole-body levels. The in vitro results demonstrate that high expression of cathepsin B in tumor cells induces effective release of the drug model from conjugates resulting in a high concentration of payload inside tumor cells. The in vivo and ex vivo images show that the conjugate releases drug model faster in the ovarian tumor than in the normal tissues. The information will enhance the understanding of enzyme-responsive polymer carriers and help to shape their design. PMID- 27198937 TI - Visuospatial planning in unmedicated major depressive disorder and bipolar disorder: distinct and common neural correlates. AB - BACKGROUND: Cognitive impairments are an important feature of both remitted and depressed major depressive disorder (MDD) and bipolar disorder (BD). In particular, deficits in executive functioning may hamper everyday functioning. Identifying the neural substrates of impaired executive functioning would improve our understanding of the pathophysiology underlying these disorders, and may eventually aid in discriminating between MDD and BD, which is often difficult during depression and remission. To date, mostly medicated MDD and BD subjects have been investigated, which may have influenced results. Therefore, we investigated executive functioning in medication-free depressed and remitted MDD and BD subjects. METHOD: We used the Tower of London (ToL) visuospatial planning task to assess behavioural performance and blood oxygen-level dependent responses in 35 healthy controls, 21 remitted MDD, 23 remitted BD, 19 depressed MDD and nine depressed BD subjects. RESULTS: Visuospatial planning per se was associated with increased frontostriatal activity in depressed BD compared to depressed MDD. In addition, post-hoc analyses indicated that visuospatial planning load was associated with increased parietal activity in depressed compared to remitted subjects, and BD compared to MDD subjects. Task performance did not significantly differ between groups. CONCLUSIONS: More severely affected, medication-free mood disorder patients require greater parietal activity to perform in visuospatial planning, which may be compensatory to maintain relatively normal performance. State-dependent frontostriatal hyperactivity during planning may be a specific BD characteristic, providing clues for further characterization of differential pathophysiology in MDD v. BD. This could potentially provide a biomarker to aid in the differentiation of these disorders. PMID- 27198935 TI - The Role of Childhood Infections and Immunizations on Childhood Rhabdomyosarcoma: A Report From the Children's Oncology Group. AB - BACKGROUND: Rhabdomyosarcoma (RMS) is a rare, highly malignant tumor arising from primitive mesenchymal cells that differentiate into skeletal muscle. Relatively little is known about RMS susceptibility. Based on growing evidence regarding the role of early immunologic challenges on RMS development, we evaluated the role of infections and immunizations on this clinically significant pediatric malignancy. PROCEDURE: RMS cases (n = 322) were enrolled from the third trial coordinated by the Intergroup Rhabdomyosarcoma Study Group. Population-based controls (n = 322) were pair matched to cases on race, sex, and age. The following immunizations were assessed: diphtheria, pertussis, and tetanus (DPT); measles, mumps, and rubella; and oral polio vaccine. We also evaluated if immunizations were complete versus incomplete. We examined selected infections including chickenpox, mumps, pneumonia, scarlet fever, rubella, rubeola, pertussis, mononucleosis, and lung infections. Conditional logistic regression models were used to calculate an odds ratio (OR) and 95% confidence interval (CI) for each exposure, adjusted for maternal education and total annual income. RESULTS: Incomplete immunization schedules (OR = 5.30, 95% CI: 2.47-11.33) and incomplete DPT immunization (OR = 1.56, 95% CI: 1.06-2.29) were positively associated with childhood RMS. However, infections did not appear to be associated with childhood RMS. CONCLUSIONS: This is the largest study of RMS to date demonstrating a possible protective effect of immunizations against the development of childhood RMS. Further studies are needed to validate our findings. Our findings add to the growing body of literature, suggesting a protective role of routine vaccinations in childhood cancer and specifically in childhood RMS. PMID- 27198938 TI - Thickness-induced structural phase transformation of layered gallium telluride. AB - The thickness-dependent electronic states and physical properties of two dimensional materials suggest great potential applications in electronic and optoelectronic devices. However, the enhanced surface effect in ultra-thin materials might significantly influence the structural stability, as well as the device reliability. Here, we report a spontaneous phase transformation of gallium telluride (GaTe) that occurred when the bulk was exfoliated to a few layers. Transmission electron microscopy (TEM) results indicate a structural variation from a monoclinic to a hexagonal structure. Raman spectra suggest a critical thickness for the structural transformation. First-principle calculations and thermodynamic analysis show that the surface energy and the interlayer interaction compete to dominate structural stability in the thinning process. A two-stage transformation process from monoclinic (m) to tetragonal (T) and then from tetragonal to hexagonal (h) is proposed to understand the phase transformation. The results demonstrate the crucial role of interlayer interactions in the structural stability, which provides a phase engineering strategy for device applications. PMID- 27198939 TI - Sleep disturbance as a proximal predictor of suicidal intent in recently hospitalized attempters. AB - OBJECTIVES: Insomnia and short self-reported sleep duration are associated with suicidality, adjusting for concurrent depression. Yet, it is unknown whether they correlate with attempters' suicidal intent and the lethality of suicidal acts. This cross-sectional study in hospitalized suicide attempters aimed to investigate whether temporally proximal self-reported sleep disturbance predicts suicidal intent or exerts mediatory effects. METHODS: Attempters were retrospectively assessed for insomnia severity (Athens Insomnia Scale [AIS]) and average night sleep duration (ANSD) for 2 weeks preceding attempt. The effects of insomnia or ANSD on suicidal intent (Beck's Suicide Intent Scale [BSIS]) were explored in multiple regressions. Mediatory effects were investigated in structural equation models (SEMs). RESULTS: A total of 127 adults (59.8% females) were interviewed within two weeks post-suicide attempt. Major psychiatric diagnoses included affective, psychotic, and alcohol-related disorders. Of the participants, 38.6% had current major depression (MDE). A total of 62.2% reported insomnia (AIS >= 6); 42.5% reported short ANSD (<=5 hours). BSIS was predicted by AIS (p = 0.034), short ANSD (p = 0.015), or insomnia with short ANSD (p = 0.006). In SEMs, indirect effects of current MDE, affective disorder, and alcohol-related disorder diagnoses on BSIS via AIS tested significant; both AIS and short ANSD partially mediated the effect of age on BSIS. CONCLUSION: Insomnia, short ANSD, and, in particular, insomnia with short ANSD proximally predicted suicidal intent in recent attempters. The effects of current depression and affective and alcohol related disorder diagnoses on suicidal intent were partially mediated by insomnia; both insomnia and short ANSD partially mediated the effect of age on suicidal intent. Therefore, management of sleep disturbance in at-risk subjects is important, as it may reduce unfavorable outcomes of suicidal acts. PMID- 27198940 TI - Sleep-disordered breathing among acute ischemic stroke patients in Brazil. AB - OBJECTIVES: Sleep-disordered breathing (SDB) is very common in acute stroke patients and has been related to poor outcome. However, there is a lack of data about the association between SDB and stroke in developing countries. The study aims to characterize the frequency and severity of SDB in Brazilian patients during the acute phase of ischemic stroke; to identify clinical and laboratorial data related to SDB in those patients; and to assess the relationship between sleep apnea and functional outcome after six months of stroke. METHODS: Clinical data and laboratorial tests were collected at hospital admission. The polysomnography was performed on the first night after stroke symptoms onset. Functional outcome was assessed by the modified Rankin Scale (mRS). RESULTS: We prospectively evaluated 69 patients with their first-ever acute ischemic stroke. The mean apnea-hypopnea index (AHI) was 37.7 +/- 30.2. Fifty-three patients (76.8%) exhibited an AHI >= 10 with predominantly obstructive respiratory events (90.6%), and thirty-three (47.8%) had severe sleep apnea. Age (OR: 1.09; 95% CI: 1.03-1.15; p= 0.004) and hematocrit (OR: 1.18; 95% CI: 1.03-1.34; p= 0.01) were independent predictors of sleep apnea. Age (OR: 1.13; 95% CI: 1.03-1.24; p= 0.01), body mass index (OR: 1.54; 95% CI: 1.54-2.18; p= 0.01), and hematocrit (OR: 1.19; 95% CI: 1.01-1.40; p= 0.04) were independent predictors of severe sleep apnea. The National Institutes of Health Stroke Scale (NIHSS; OR: 1.30; 95% CI: 1.1-1.5; p= 0.001) and severe sleep apnea (OR: 9.7; 95% CI: 1.3-73.8; p= 0.03) were independently associated to mRS >2 at six months, after adjusting for confounders. CONCLUSION: Patients with acute ischemic stroke in Brazil have a high frequency of SDB. Severe sleep apnea is associated with a poor long-term functional outcome following stroke in that population. PMID- 27198941 TI - Sleep duration and risk of myocardial infarction and all-cause death in a Chinese population: the Kailuan study. AB - OBJECTIVE: Although sleep is one of the most important health-related factors, the association of sleep duration with incidence of myocardial infarction or all cause death has not been fully understood, especially in the general Chinese population. The objective of this study was to explore the relationship between sleep duration and risk of myocardial infarction and all-cause death in China. METHODS: Out of the 101,510 participants who were originally included into the Kailuan prospective cohort study and followed up for an average of 3.98 years, 95,903 participants were actually sampled to evaluate the impacts of sleep duration on myocardial infarction and all-cause death. Sleep duration was categorized as <=5, 6, 7, and 8 hours/night, and >=9 hours per night. Cox proportional hazards models were used to analyze the association of sleep duration with the incidence of myocardial infarction and all-cause death. RESULTS: After a mean follow-up period of 3.98 years, 423 participants developed myocardial infarction and 1793 participants died. A U-shape association between sleep duration and all-cause death was found. The age- and gender-adjusted hazard ratios (95% confidence interval [CI]) of all-cause death (with seven hours of daily sleep being considered for the reference group) for individuals reporting <=5, 6, and 8 hours, and >=9 hours were 1.29 (1.08-1.55), 0.97 (0.82-1.14), 1.11 (0.97-1.27), and 1.77 (1.31-2.38), respectively, with a p <= 0.01. However, no significant association was seen between sleep duration and myocardial infarction. CONCLUSION: Both short and long duration of sleep might be potential predictors/markers for all-cause death, but not for myocardial infarction. PMID- 27198942 TI - Clinical course of H1N1-vaccine-related narcolepsy. AB - OBJECTIVE: To follow and analyze the clinical course and quality of life of Pandemrix H1N1-vaccine-related narcolepsy (pNT1). METHODS: Twenty-six drug-naive confirmed pNT1 subjects completed Epworth Sleepiness Scale (ESS), Ullanlinna Narcolepsy Scale (UNS), Swiss Narcolepsy Scale (SNS), Rimon's Brief Depression scale (RDS), and WHO-5 Well-being index questionnaires near the disease onset and in a follow-up a minimum of two years later. The number of cataplexies and body mass index (BMI) were recorded. The effects of hypocretin-1 levels and sleep recording results were analyzed. The findings at the follow-up visit were compared with 25 non-vaccine-related type 1 narcolepsy (NT1) subjects. RESULTS: In pNT1, RDS score decreased significantly (mean 10.2, SD 4.7 vs mean 6.7, SD 4.5, p = 0.003). Median of BMI increased from 20.8 kg m(-2) to 23.4 kg m(-2), p <0.001. There were no significant differences in other sleep scores. However, deviation and range in questionnaire scores at the follow-up were wide. Subjects with very low or undetectable hypocretin-1 levels had worse scores in UNS (mean 26.4, SD 6.95 vs mean 19.1, SD 3.83, p = 0.006) and ESS (mean 17.9, SD = 4.29 vs mean 14.1, SD = 3.70, p = 0.047) than those with hypocretin-1 levels of 20-110 pg/mL. Most disabling symptoms were excessive daytime sleepiness and disturbed sleep. There were no significant differences between the scores in pNT1 and NT1. CONCLUSIONS: Clinical course of pNT1 is heterogeneous but the evolution of pNT1 seems similar to NT1. Lower hypocretin levels in pNT1 are associated with a more severe phenotype. PMID- 27198943 TI - Continuous positive airway pressure and survival of very elderly persons with moderate to severe obstructive sleep apnea. AB - OBJECTIVE: There is evidence of a beneficial effect of long-term continuous positive airway pressure (CPAP) on survival in elderly persons with obstructive sleep apnea (OSA), although the usual age cut off is between 60 and 70 years of age. Our objective was to determine this effect in very elderly patients (ie, those >=80 years of age). METHODS: An observational study of a historic cohort of very elderly persons with moderate to severe OSA (apnea-hypopnea index >=20) and the effect of long-term CPAP on their survival was performed. Two groups were formed: one prescribed CPAP treatment (>=4 hours per night), and one without CPAP treatment. Survival analyses, including Kaplan-Meier curves and Cox models, were carried out to determine the association of long-term CPAP with longer survival, RESULTS: A total of 155 very elderly persons (84 men and 71 women, mean age 81.5 +/- 1.5 years) were followed up for 53 months (interquartile range, 41-77 months); 83 deaths occurred. CPAP was prescribed to 132 patients, and adherence was observed in 79 (60%). Kaplan-Meier curves showed longer survival in the treated OSA group (91 months, 95% confidence interval [CI] = 76-106) than in the untreated OSA group (52 months, 95% CI 41-64), which was statistically significant (log-rank 16.9, p < 0.0001). Although history of stroke was significantly associated with higher mortality (hazard ratio [HR] = 2.18, 95% CI = 1.14-4.17, p = 0.02), CPAP treatment was associated with higher survival rates (HR = 0.46, 95% CI = 0.27-0.78, p = 0.004) in an adjusted Cox analysis. CONCLUSIONS: CPAP treatment might be associated with a longer survival in very elderly persons with moderate to severe OSA. PMID- 27198944 TI - It's not just obstructive sleep apnea. PMID- 27198946 TI - Autonomic dysfunction in primary sleep disorders. AB - The autonomic nervous system plays an important role in the coordination of many important physiologic functions during sleep. Many patients with untreated sleep disorders will describe symptoms of autonomic impairment, and a majority of patients with autonomic impairment have some form of sleep disorder. This article will explore possible explanations for this connection, as well as review the current literature on autonomic impairment in common primary sleep disorders including obstructive sleep apnea, insomnia, restless legs syndrome, periodic limb movement disorder, narcolepsy, and rapid eye movement sleep behavior disorder. PMID- 27198945 TI - The influence of school time on sleep patterns of children and adolescents. AB - OBJECTIVE: This epidemiological study evaluated the impact of school time on sleep parameters of children and adolescents. METHODS: This cross-sectional study involved 639 elementary and high school students (mean age 13.03 years, range 8 18, 58.5% female) from the south of Brazil. Participants answered the Morningness Eveningness Questionnaire (MEQ), and were asked about their sleeping habits on weekdays and weekends. Sleep deficit was defined as the difference between sleep duration on weekdays and weekends. RESULTS: The morning-school-time students presented significantly higher age, bedtime and wake up differences, sleep deficits, and social jetlag. The sleep deficit presented by girls was greater than that observed in boys of the same age. The difference between weekday and weekend waking times was also significantly greater in girls than in boys aged 13 18 years. Sleep deficit was significantly positively correlated with age and differences in wake up times, and significantly negatively correlated with MEQ scores, social jetlag, difference between weekday and weekend bedtimes, midpoint of sleep on weekends, and midpoint of sleep on weekends corrected for sleep deficit. A step-by-step multivariate logistic regression identified social jetlag, the difference between waking times on weekdays and weekends, and the midpoint of sleep on weekends as significant predictors of sleep deficit (Adjusted R(2) = 0.95; F = 1606.87; p <0.001). CONCLUSION: The results showed that school time influences the sleep parameters. The association of school schedules and physiological factors influence the sleep/wake cycle. PMID- 27198947 TI - Efficacy of gabapentin enacarbil in adult patients with severe primary restless legs syndrome. AB - AIM: Assess efficacy and tolerability of gabapentin enacarbil (GEn) in adults with severe primary restless legs syndrome (RLS). METHODS: We pooled data from three 12-week, double-blind, placebo-controlled, randomized trials (NCT00298623, NCT00365352, NCT01332305) across GEn 600-mg, GEn 1200-mg, and placebo treatment groups for severe primary RLS (baseline International Restless Legs Scale (IRLS) total score >=24). Co-primary end points at week 12 were mean change from baseline in IRLS total score and proportion of responders ("much"/very much" improved) on the investigator-rated Clinical Global Impression - Improvement (CGI I) Scale. Outcomes for individual IRLS items (eg, sleep, mood, quality of life, pain, safety) were assessed. RESULTS: A total of 309 patients had severe primary RLS (placebo, n = 110; GEn 600 mg, n = 80; GEn 1200 mg, n = 119). GEn 600 mg and 1200 mg significantly improved least-squares mean IRLS total scores versus placebo at week 12 (placebo, -12.3; GEn 600 mg, -16.3; GEn 1200 mg, -18.0; treatment difference vs. placebo, both p <0.01). Significantly more patients with severe primary RLS treated with GEn 600 mg (64%) and 1200 mg (74%) were CGI-I responders at week 12 versus placebo (42%; p <0.01 for both GEn doses). Both GEn doses led to significant improvements in the other outcomes explored versus placebo at week 12. The most frequent treatment-emergent adverse events (TEAEs) were somnolence (GEn, 21-24%; placebo, 3%) and dizziness (GEn, 14-19%; placebo, 3%). CONCLUSIONS: GEn (600 mg or 1200 mg) once daily significantly improved RLS symptoms and consequences of these symptoms in severe primary RLS. The most frequent TEAEs were somnolence and dizziness. PMID- 27198948 TI - Mood disorders in healthy elderly with obstructive sleep apnea: a gender effect. AB - OBJECTIVE: Previous studies have suggested an association between obstructive sleep apnea (OSA) and anxiety and depression, but it remains unclear as to whether this is due to OSA or other factors. The aim of this study was to evaluate this association in a large sample of healthy elderly with unrecognized OSA. METHODS: 825 healthy elderly (aged >=65 years) undergoing clinical, respiratory home polygraphic study and completion of questionnaires related to depression, anxiety and sleepiness were examined. According to the apnea-hypopnea index (AHI), the subjects were stratified into no-OSA, mild-moderate and severe OSA cases. RESULTS: Anxiety was present in 38% of the sample and depression in 8%. Anxiolytic treatment was reported by 9% of the population and antidepressant treatment in 5%. Women had high scores for anxiety and depression and they were more frequently taking anxiolytic and antidepressant medications. No differences were found for anxiety and depression scores and medication intake in the three groups of subjects stratified according to the AHI. Regression analyses adjusted for age, gender, body mass index, hypertension (HT), AHI, and indices of hypoxemia revealed that females were 5.44 times more likely to have depression with a low contribution of the time with SaO2 < 90%. CONCLUSIONS: In a large sample of healthy elderly with OSA, neither the existence nor the severity of the OSA was associated with anxiety and depression score, with women having higher anxiety and depression scores. This finding supports the hypothesis that depressive symptoms originate from factors other than measures of OSA severity. PMID- 27198949 TI - Sleep bruxism in children: sleep studies correlate poorly with parental reports. AB - The prevalence of sleep bruxism (SB) is usually reported as highest during childhood and decreases with age. However, this is based on parental reports and self-reports in the absence of quantitative data. Moreover, although SB signs, symptoms, and cutoff criteria have been established in the adult population, they remain unassessed in the pediatric population. OBJECTIVES: This study aims to classify SB in children according to sleep variables and rhythmic masticatory muscle activity (RMMA) frequency indexes and to determine associations with objective signs and symptoms of SB in comparison with parental reports. MATERIALS AND METHODS: Thirty-two children (11.5 +/- 0.3 years) recruited at the orthodontic clinic underwent a dental assessment and ambulatory sleep recording (type II). Parents responded to a validated screening questionnaire on tooth clenching and grinding. A two-step cluster analysis was performed to classify participants into RMMA frequency groups, as described subsequently, followed by one-way analysis of variance (ANOVA) to compare groups. Fisher's exact test was performed for analyzing the associations between the signs and symptoms according to RMMA. RESULTS: Three RMMA frequency groups were identified: low (n = 12), moderate-high (n = 13), and control (n = 7). Between-group comparisons for episodes per hour and bursts/hour were significant (p <0.001). No relationships were found between RMMA (presence/absence) and clinically assessed tooth wear or reports of tooth clenching or grinding or craniofacial complaints. CONCLUSIONS: RMMA frequency classification differs slightly between children and adults. No association was observed between parental reports and RMMA, suggesting the need to improve parental knowledge of children's SB. PMID- 27198951 TI - Evaluating the clinical value of oscillatory cardiopulmonary coupling in patients with obstructive sleep apnea hypopnea syndrome by impedance cardiogram. AB - OBJECTIVES: For patients with obstructive sleep apnea hypopnea syndrome (OSAHS), chronic inflammation and hemodynamic oscillations caused by respiratory events contribute to cardiovascular disease (CVD). In this study, a physiological marker named oscillatory coupling factor (OCF) exacted from cardiac output (CO) was introduced. This study aimed to evaluate the clinical value of OCF and tentatively explore its predictive value of cardiovascular prognosis in OSAHS patients. METHODS: An impedance cardiogram (ICG) was used to continuously obtain the participants' CO with simultaneous polysomnography. Participants were divided into three groups: an OSAHS-CVD- group (n = 19); an OSAHS + CVD- group (n = 34); and an OSAHS + CVD + group (n = 36). The OCF was exacted from the CO by using empirical mode decompensation-based detrended fluctuation analysis (EMD-DFA). RESULTS: The OCF values were: OSAHS + CVD + group [1.20 (0.98-1.78)] > OSAHS + CVD- group [1.14 (1.02-1.94)] > OSAHS-CVD- group [0.95 (0.56-1.16)], (p = 0.001). A Spearman test showed that OCF was positively correlated with age, apnea/hypopnea index (AHI), microarousal index (MAI), oxygen desaturation index (ODI), and negatively correlated with the lowest SpO2. Ten participants were treated by one-night continuous positive airway pressure (CPAP): their AHI decreased from 44.9 (18.0-72.9)/hour to 1.25 (0.0-7.5)/hour, and their OCF fell from 1.17 (1.10-1.69) to 1.08 (0.96-1.23) (p = 0.038). Seventy-seven participants were effectively followed up. Seven participants developed CVD events or newly diagnosed CVD; their OCFs were distributed on a relatively high level [1.18 (1.01 1.56)]. CONCLUSION: The OSAHS participants had higher OCFs than those without OSAHS, while CVD made the OCFs even higher; CPAP could rectify this change. Oscillatory coupling factor may be a physiological marker of cardiopulmonary coupling and have potential cardiovascular prognostic value for people with OSAHS. PMID- 27198952 TI - Criteria for nap identification in infants and young children using 24-h actigraphy and agreement with parental diary. AB - STUDY OBJECTIVES: The study aimed to determine if an automated algorithm, capable of batch scoring, could extract naps and other 24-h sleep-wake variables from actigraphy without the need for parental sleep diaries, which rely heavily on parental awareness of child sleep. DESIGN: A cross-sectional design was used for the study. SETTING: The study examined healthy infants/children in their home setting. PARTICIPANTS: A total of 160 infants/children in five age groups (6 months, and 1, 2, 31/2 and 5 years) participated in the study. MEASUREMENTS AND RESULTS: Participants wore actigraphs for 5-7 days, and parents completed sleep diaries over 2 consecutive days. Three criteria were applied to find the minimum sleep time (20, 30 and 40 min) yielding the best nap agreement between diaries and actigraphy for nap/no-nap identification. Best agreements were 72.1% (20 min minimum), 78.4% (20 min), 91.0% (30 min) and 93.3% (30 min) for ages 6 months, 1, 2 and 31/2 years, respectively. Kappa statistics classified nap-nap agreement as 'slight' for 6-month data but 'moderate' or 'almost perfect' for older age groups. The number of daytime naps extracted at each age group yielded no significant discrepancies between the methods. Diaries generally returned significantly earlier sleep onset, later sleep offset, longer sleep duration and fewer night wakings at 6 months and 1 and 2 years, but this was not significant at 31/2 or 5 years of age. CONCLUSIONS: Minimum age-specific sleep time thresholds are recommended to improve nap identification in actigraphy across infant and toddler age groups. The findings strengthen our confidence in the ability to collect actigraphy data in the absence of parental diaries, in 31/2- and 5-year-olds, at least. PMID- 27198953 TI - Effects of suvorexant on sleep architecture and power spectral profile in patients with insomnia: analysis of pooled phase 3 data. AB - BACKGROUND: The orexin receptor antagonist, suvorexant, is approved for treating insomnia at a maximum dose of 20 mg. We evaluated its effects on sleep architecture. METHODS: The analyses included pooled polysomnography data from two similar randomized, double-blind, placebo-controlled, 3-month trials evaluating two age-adjusted (non-elderly/elderly) dose regimes of 20/15 mg and 40/30 mg in 1482 patients with insomnia. Polysomnography was recorded at baseline and on three nights during the treatment: Night-1, Month-1, and Month-3. Effects on non REM sleep stages 1 (N1), 2 (N2), 3 (N3)/slow wave sleep (SWS), and REM sleep were evaluated. A power spectral analysis of non-REM sleep was also performed. RESULTS: Suvorexant increased the time (in minutes) spent in all sleep stages compared with placebo. When suvorexant and placebo were compared in terms of changes in percentage of total sleep time spent in each stage, there were small decreases of <=1%, <=2.2%, and <=0.8% for N1, N2, and N3/SWS on average, respectively, and an average increase of <=3.9% in REM. The largest differences from placebo were observed at Night-1 and generally diminished over time. Suvorexant reduced REM latency (number of non-REM 30-s epochs from lights-off to the first REM epoch) compared with placebo; the reduction was greater at Night-1 (~40-50 non-REM epochs) in comparison to later time points (~12-25 non-REM epochs at Month-3). The spectral analysis of non-REM showed a small decrease in power of 3-6% in the gamma and beta bands, and a small increase of 4-8% in the delta band, at Night-1 for suvorexant relative to placebo; these effects were not apparent at the later Month-1 and Month-3 time points. CONCLUSION: Overall sleep architecture appears to be preserved in insomnia patients taking suvorexant. The power spectral profile of suvorexant is generally similar to placebo. PMID- 27198954 TI - Association between stress-related sleep reactivity and cognitive processes in insomnia disorder and insomnia subgroups: preliminary results. AB - OBJECTIVE: Stress-related sleep reactivity, sleep-related cognitions, and psychological factors play an important role in insomnia. The aim was to investigate their possible association in Insomnia Disorder, insomnia subgroups, and healthy subjects. METHODS: The cross-sectional study consisted of 93 subjects who met diagnostic criteria for Insomnia Disorder according to Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) and of 30 healthy subjects. Survey instruments included the Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), Ford Insomnia Response to Stress Test (FIRST), Dysfunctional Beliefs about Sleep scale (DBAS), Beck Depression Inventory (BDI), and Zung Self-Rating Anxiety Scale (SAS). Descriptive statistics, Pearson correlations, chi(2)-test, and multiple linear regression were performed. RESULTS: FIRST and SAS best determined the insomnia subjects vs good sleepers (FIRST chi(2) = 109.6, p <0.001, SAS chi(2) = 120.3, p <0.001). FIRST was best predicted by DBAS (p <0.001), PSQI (p <0.001), and SAS by PSQI (p <0.001), ISI (p <0.05), BDI (p <0.001). In the sleep onset subgroup FIRST was related to ISI, PSQI, and DBAS and in the combined subgroup with DBAS. In both subgroups SAS was related to PSQI, ISI, and BDI. CONCLUSIONS: Findings suggest potential implications: (1) among the factors that may contribute to insomnia, stress-related sleep reactivity, and psychological factors, such as anxiety symptoms, may distinguish insomnia subjects from good sleepers; (2) sleep reactivity and sleep-related cognitions seem interrelated, unhelpful beliefs may affect the stress reactivity; (3) psychological factors may influence sleep quality and the severity of insomnia; (4) these important sleep-related variables may have similar associations in insomnia subgroups; they may constitute the core factors for insomnia development and maintenance. PMID- 27198950 TI - The association between sleep-disordered breathing and aortic stiffness in a community cohort. AB - OBJECTIVE: Sleep-disordered breathing is associated with hypertension and cardiovascular disease. Increased aortic stiffness is one possible linking mechanism. We evaluated the association between sleep-disordered breathing and aortic stiffness in a community-based sample. METHODS: Our community-based cross sectional observational study included 381 participants from the Framingham Heart Study (55% women, mean age 58.0 S.D. = 9.4 years, 51% ethnic minorities). Polysomnographically derived apnea-hypopnea index and CT90% (cumulative % sleep time with oxyhemoglobin saturation <90%) quantified sleep-disordered breathing severity. Carotid-femoral pulse wave velocity, the gold-standard measure of aortic stiffness, was calculated using arterial applanation tonometry-derived waveforms and body surface measured transit distance. We assessed associations between sleep-disordered breathing and carotid-femoral pulse wave velocity using multivariable regression. We adjusted for age, sex, race, body mass index, diabetes, alcohol consumption, hormone replacement therapy, cholesterol/high density lipoprotein, lipid-lowering therapy, anti-hypertensive medication, smoking, hypertension, and prevalent cardiovascular disease. RESULTS: After multivariable adjustment, carotid-femoral pulse wave velocity was associated with both apnea-hypopnea index (beta = 0.03, 95% CI: 0.002-0.07, p= 0.04) and CT90% (beta = 0.05, 95% CI: 0.005-0.1, p= 0.03). The adjusted mean carotid-femoral pulse wave velocity was 9.43 (95% CI: 9.12-9.74), 9.76 (95% CI: 9.25-10.26), and 10.15 (95% CI: 9.37-10.92) m/s, respectively, in subjects with apnea-hypopnea index <5, 5-14.9, and >=15 events/h. CONCLUSIONS: In a community-based sample of middle aged and older men and women, sleep-disordered breathing was associated with increased carotid-femoral pulse wave velocity, a strong predictor of cardiovascular risk. PMID- 27198955 TI - Relationship between insomnia symptoms, perceived stress and coping strategies in subjects with arterial hypertension: psychological factors may play a modulating role. AB - OBJECTIVE: The aim of the study was to evaluate perceived stress and coping strategies in people with hypertension, according to the presence of insomnia symptoms and by using a set of variables that included anxiety and depressive symptoms evaluation. METHODS: A total of 371 hypertensive patients were enrolled during their first visit to the Hypertension Outpatient Unit. The Perceived Stress Scale (PSS), Brief-COPE, Insomnia Severity Index (ISI), Beck Depression Inventory (BDI), Self-rating Anxiety Scale (SAS), and State-Trait Anxiety Inventory (STAI) were administered. Patients with other sleep disorders or with incomplete data (n = 41) were excluded. RESULTS: Data from 330 hypertensive patients were analyzed (males 51%, mean age 57 +/- 13 years). Those with insomnia symptoms (n = 70, 21%) were older (p = 0.02), more frequently females (p = 0.01), and presented with higher PSS (p < 0.001), BDI (p < 0.0001), SAS (p = 0.0003), and STAI (p < 0.0001) scores than those without insomnia symptoms. In a linear regression trait, anxiety (p < 0.0001) and depressive symptoms (p < 0.05) were independent predictors of high PSS. Patients with insomnia symptoms showed lower scores in coping strategies, such as positive reframing (p = 0.03) and emotional support (p = 0.04), and an increased score in behavioral disengagement (p = 0.03). Trait anxiety and insomnia severity were independent predictors of less effective coping strategies. CONCLUSIONS: People with hypertension and insomnia symptoms showed higher perceived stress and less effective coping strategies than non-insomniacs; psychological factors such as trait anxiety and depressive symptoms may play a modulating role in these relationships. Prevention and treatment of insomnia symptoms and psychological factors should receive high attention for people with hypertension. PMID- 27198956 TI - Prevalence of insomnia and its risk factors in older individuals: a community based study in four cities of Hebei Province, China. AB - OBJECTIVE: To examine the epidemiology of sleep problems and insomnia among the community older individuals in Hebei Province, China, and to investigate the potential sociodemographic and clinical correlates and medication use. METHODS: This cross-sectional study was conducted with community adults, aged 60 years or older, who resided in four major cities in Hebei province. Basic sociodemographic and clinical data were collected and analyzed. A total of 3176 older adults (1292 men, 70.2 +/- 6.8 years; 1884 women, 68.8 +/- 6.7 years) were interviewed. All of the participants were interviewed with a standardized questionnaire and underwent insomnia screening. RESULTS: The prevalence of insomnia was 37.75%. The most common type of sleep disturbance was difficulty maintaining sleep, followed by difficulty initiating sleep and early morning awakening. Never smoking, experiencing the loss of a parent, a history of coronary heart disease, and depression symptoms were independent risk factors for insomnia in men. Occasional drinking was an independent protective factor against insomnia in men. Older age, depression symptoms, a history of cerebral hemorrhage, hyperlipidemia, living without a spouse, and having mild cognitive impairment were independent risk factors for insomnia in women. Only 11.1% of the sample with insomnia were taking sleeping medications regularly. CONCLUSION: Insomnia is highly prevalent among the community older population in Hebei Province. The percentage of individuals regularly taking sleeping medication is low among those with insomnia. Individuals with complaints of insomnia frequently have poor physical and mental health and may need more medical attention. Comprehensive measures that involve psychosocial and personal behaviors should be implemented to alleviate insomnia in older individuals. PMID- 27198959 TI - In Memoriam, Elio Lugaresi, MD (July 1, 1926-December 22, 2015). PMID- 27198960 TI - Reversible thrombotic aortic valve restenosis after valve-in-valve transcatheter aortic valve replacement. AB - Thrombotic aortic valve restenosis following transcatheter aortic valve replacement (TAVR) has not been extensively reported and the rates of TAVR valve thrombosis are not known. We present three cases of valve-in-valve (VIV) restenosis following TAVR with the balloon expandable transcatheter heart valves, presumably due to valve thrombosis that improved with anticoagulation. (c) 2016 Wiley Periodicals, Inc. PMID- 27198966 TI - Polymer globule with fractal properties caused by intramolecular nanostructuring and spatial constrains. AB - By means of computer simulation, we studied macromolecules composed of N dumbbell amphiphilic monomer units with attractive pendant groups. In poor solvents, these macromolecules form spherical globules that are dense in the case of short chains (the gyration radius RG~N(1/3)), or hollow inside and obey the RG~N(1/2) law when the macromolecules are sufficiently long. Due to the specific intramolecular nanostructuring, the vesicle-like globules of long amphiphilic macromolecules posses some properties of fractal globules, by which they (i) could demonstrate the same scaling statistics for the entire macromolecule and for short subchains with m monomer units and (ii) possess a specific territorial structure. Within a narrow slit, the globule loses its inner cavity, takes a disk-like shape and scales as N(1/2) for much shorter macromolecules. However, the field of end-to end distance r(m) ~m(1/2) dependence for subchains becomes visibly smaller. The results obtained were compared with the homopolymer case. PMID- 27198965 TI - Automated alignment of perioperative MRI scans: A technical note and application in pediatric epilepsy surgery. AB - Conventional image registration utilizing brain voxel information may be erroneous in a neurosurgical setting due to pathology and surgery-related anatomical distortions. We report a novel application of an automated image registration procedure based on skull segmentation for magnetic resonance imaging (MRI) scans acquired before, during and after surgery (i.e., perioperative). The procedure was implemented to assist analysis of intraoperative brain shift in 11 pediatric epilepsy surgery cases, each of whom had up to five consecutive perioperative MRI scans. The procedure consisted of the following steps: (1) Skull segmentation using tissue classification tools. (2) Estimation of rigid body transformation between image pairs using registration driven by the skull segmentation. (3) Composition of transformations to provide transformations between each scan and a common space. The procedure was validated using locations of three types of reference structural landmarks: the skull pin sites, the eye positions, and the scalp skin surface, detected using the peak intensity gradient. The mean target registration error (TRE) scores by skull pin sites and scalp skin rendering were around 1 mm and <1 mm, respectively. Validation by eye position demonstrated >1 mm TRE scores, suggesting it is not a reliable reference landmark in surgical scenarios. Comparable registration accuracy was achieved between opened and closed skull scan pairs and closed and closed skull scan pairs. Our procedure offers a reliable registration framework for processing intrasubject time series perioperative MRI data, with potential of improving intraoperative MRI-based image guidance in neurosurgical practice. Hum Brain Mapp 37:3530-3543, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27198961 TI - Size quantization of Dirac fermions in graphene constrictions. AB - Quantum point contacts are cornerstones of mesoscopic physics and central building blocks for quantum electronics. Although the Fermi wavelength in high quality bulk graphene can be tuned up to hundreds of nanometres, the observation of quantum confinement of Dirac electrons in nanostructured graphene has proven surprisingly challenging. Here we show ballistic transport and quantized conductance of size-confined Dirac fermions in lithographically defined graphene constrictions. At high carrier densities, the observed conductance agrees excellently with the Landauer theory of ballistic transport without any adjustable parameter. Experimental data and simulations for the evolution of the conductance with magnetic field unambiguously confirm the identification of size quantization in the constriction. Close to the charge neutrality point, bias voltage spectroscopy reveals a renormalized Fermi velocity of ~1.5 * 10(6) m s( 1) in our constrictions. Moreover, at low carrier density transport measurements allow probing the density of localized states at edges, thus offering a unique handle on edge physics in graphene devices. PMID- 27198967 TI - Chromoselective Photocatalysis: Controlled Bond Activation through Light-Color Regulation of Redox Potentials. AB - Catalysts that can be regulated in terms of activity and selectivity by external stimuli may allow the efficient multistep synthesis of complex molecules and pharmaceuticals. Herein, we report the light-color regulation of the redox potential of a photocatalyst to control the activation of chemical bonds. Light color control of the redox power of a photocatalyst introduces a new selectivity parameter to photoredox catalysis: Instead of changing the catalyst or ligand, alteration of the color of the visible-light irradiation adjusts the selectivity in catalytic transformations. By using this principle, the selective activation of aryl-halide bonds for C-H arylation and the sequential conversion of functional groups with different reduction potentials is possible by simply applying different colors of light for excitation of the photocatalyst. PMID- 27198969 TI - Primary total hip arthroplasty using 3rd generation ceramic-on-ceramic articulation. AB - PURPOSE: Ceramic-on-ceramic (CoC) is currently a popular bearing combination in young patients in primary total hip arthroplasty (THA). The purpose of this study was to evaluate clinical and radiographic results and complications of cementless THA with 3rd generation CoC articulation. MATERIALS AND METHODS: From April 2001 to January 2008, 310 primary THAs were performed in 300 patients using 3rd generation CoC articulation. The mean follow-up period was 8.9 years and the mean age at index surgery was 54.6 years. Patient clinical outcome was evaluated with the Harris Hip Score. Radiographic evaluations was performed to analyse osteolysis, implant fixation and loosening. RESULTS: Mean Harris Hip Score at last follow-up was 95.4 (76-100). Radiographic analysis demonstrated no evidence of stem or cup loosening and there were no cases of osteolysis. Ceramic wear was not detectable on the plain radiograph. Complications requiring revision occurred in 12 cases; 2 ceramic head fractures, 4 dislocations, 2 deep infections and 4 cases of periprosthetic fracture. The cohort had an overall revision rate of 3.9%. CONCLUSIONS: Clinical outcomes using cementless THA with 3rd generation CoC articulation were satisfactory. Although the mechanical properties of ceramic materials have improved, there are still problems such as ceramic fracture and squeaking. More clinical study and investigation for alternative bearing are necessary to reduce complications. 4th generation CoC or ceramic on cross linked polyethylene may address some of these issues. PMID- 27198968 TI - Nanomolar pyrophosphate detection and nucleus staining in living cells with simple terpyridine-Zn(II) complexes. AB - Great efforts have been made to develop fluorescent probes for pyrophosphate (PPi) detection. Nucleus staining with fluorescence microscopy has been also widely investigated. But fluorescent probes for PPi detection with high sensitivity in water medium and nucleus staining with low-cost non-precious metal complexes in living cells are still challenging. Herein, we report simple terpyridine-Zn(II) complexes for selective nanomolar PPi detection over ATP and ADP in water based on aggregation induced emission (AIE) and intramolecular charge transfer (ICT). In addition, these terpyridine-Zn(II) complexes were successfully employed for nucleus staining in living cells. These results demonstrated simply obtained terpyridine-Zn(II) complexes are powerful tool for PPi detection and the development of PPi-related studies. PMID- 27198970 TI - Quality of reduction and prognosis of developmental dysplasia of the hip: a retrospective study. AB - INTRODUCTION: Using limited MRI we evaluated the quality of closed reduction and prognosis in a group of patients with developmental dysplasia of the hip (DDH). METHODS: Limited MRI was performed on 28 DDH patients (41 hips) after closed reduction. All the hips were divided into deep and incomplete concentric reduction groups according to the femoral head-acetabular distance (FAD) and the shape of the labrum on limited MRI. The abduction angle of the hips, and the initial and final acetabular index (AI) were measured. Presence or absence of the ossification centre of the femoral head before treatment, the Tonnis classification and avascular necrosis of the femoral head and types (Bucholz and Ogden type) were recorded. The data of the 2 groups were analysed with SPSS software. RESULTS: We found no significant differences in age, gender, side, preoperative ossification centre of the femoral head, preoperative AI, decreased postoperative AI and abduction angles of hips between the 2 groups. There were significant statistical differences in the preoperative Tonnis grade, FAD after reduction, AI at the final follow-up, severe residual deformity and severe avascular necrosis of the femoral head (p<0.05). The cure rate showed a significant trend (p = 0.052). CONCLUSIONS: Limited MRI enables effective determination of the quality of reduction immediately after closed reduction. The prognosis of the deep concentric reduction group was better than the group with incomplete concentric reduction. PMID- 27198971 TI - Sodium trimetaphosphate enhances the effect of 250 p.p.m. fluoride toothpaste against enamel demineralization in vitro. AB - This in vitro study investigated the effect of sodium trimetaphosphate (TMP), added to toothpaste containing 250 p.p.m. fluoride, on enamel demineralization. Bovine enamel blocks (n = 96) were subjected to five pH cycles over a 7-d period and treatment with suspensions of toothpastes containing 0, 250, 500, and 1,100 p.p.m. fluoride (as sodium fluoride), as well as with 250 p.p.m. fluoride containing TMP at 0.25, 0.5, 1.0, and 3.0%. Treatment with toothpaste suspensions was performed under agitation twice a day, for 1 min. Surface and cross-sectional hardness, and fluoride firmly bound to enamel, were quantified. Data were subjected to one-way anova, followed by Tukey's test. Low-fluoride toothpastes containing TMP at 0.25-1.0% resulted in enamel mineral loss similar to that seen for the toothpaste containing 1,100 p.p.m. fluoride. Also, the addition of TMP to the toothpaste containing 250 p.p.m. fluoride promoted enamel fluoride concentrations similar to those obtained for the 500 p.p.m. fluoride group. The toothpaste containing 250 p.p.m. fluoride and 0.25% TMP led to the lowest mineral loss among all groups. It was concluded that the addition of as little as 0.25% TMP to a toothpaste containing 250 p.p.m. fluoride can reduce enamel demineralization to levels similar to those seen for a conventional toothpaste containing 1,100 p.p.m. fluoride, in vitro. PMID- 27198972 TI - Prediction of beef color using time-domain nuclear magnetic resonance (TD-NMR) relaxometry data and multivariate analyses. AB - Time-domain nuclear magnetic resonance and chemometrics were used to predict color parameters, such as lightness (L*), redness (a*), and yellowness (b*) of beef (Longissimus dorsi muscle) samples. Analyzing the relaxation decays with multivariate models performed with partial least-squares regression, color quality parameters were predicted. The partial least-squares models showed low errors independent of the sample size, indicating the potentiality of the method. Minced procedure and weighing were not necessary to improve the predictive performance of the models. The reduction of transverse relaxation time (T2 ) measured by Carr-Purcell-Meiboom-Gill pulse sequence in darker beef in comparison with lighter ones can be explained by the lower relaxivity Fe2+ present in deoxymyoglobin and oxymyoglobin (red beef) to the higher relaxivity of Fe3+ present in metmyoglobin (brown beef). These results point that time-domain nuclear magnetic resonance spectroscopy can become a useful tool for quality assessment of beef cattle on bulk of the sample and through-packages, because this technique is also widely applied to measure sensorial parameters, such as flavor, juiciness and tenderness, and physicochemical parameters, cooking loss, fat and moisture content, and instrumental tenderness using Warner Bratzler shear force. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27198973 TI - Improvements in health-related quality of life with liraglutide 3.0 mg compared with placebo in weight management. AB - Obesity has a negative impact on health-related quality of life (HRQoL). The SCALE Obesity and Prediabetes study investigated the effect of liraglutide 3.0 mg, as adjunct to diet and exercise, on HRQoL in patients with obesity [body mass index (BMI) >= 30 kg m(-2) ] or overweight (BMI >= 27 kg m(-2) ) with comorbidity. Participants were advised on a 500 kcal d(-1) deficit diet and a 150 min week(-1) exercise programme and were randomised 2:1 to once-daily subcutaneous liraglutide 3.0 mg or placebo. HRQoL was assessed using the Impact of Weight on Quality of Life-Lite (IWQOL-Lite) and Short-Form 36 (SF-36) v2 health questionnaires. Individuals on liraglutide 3.0 mg (n = 2046) had significantly greater improvements in IWQOL-Lite total score (10.6 +/- 13.3) vs. placebo (n = 1020) (7.7 +/- 12.8) and SF-36 physical (PCS) and mental (MCS) component summary scores (PCS, 3.6 +/- 6.8; MCS, 0.2 +/- 8.1) vs. placebo (PCS, 2.2 +/- 7.7; MCS, -0.9 +/- 9.1). The estimated treatment differences were IWQOL Lite total score 3.1 (95% CI: 2.2; 4.0), P < 0.0001; SF-36 PCS 1.7 (95% CI: 1.2; 2.2), P < 0.0001 and MCS 0.9 (95% CI: 0.3; 1.5), P = 0.003. All subscales of the IWQOL-Lite and SF-36 were significantly improved with liraglutide 3.0 mg vs. placebo. More patients on liraglutide 3.0 mg experienced meaningful improvement on the IWQOL-Lite total (P < 0.0001) and the SF-36 PCS (P < 0.0001) scores. PMID- 27198974 TI - Functional nanocarriers by miniaturization of polymeric materials. PMID- 27198975 TI - Evaluation of the Psychometric Properties of the Mental Vulnerability Questionnaire in Undergraduate Students. AB - PURPOSE: Translate, adapt the language, and assess the psychometric properties of the Mental Vulnerability Questionnaire (MVQ) in a Portuguese population sample of young adults. DESIGN AND METHODS: A psychometric validation study was performed. The sample comprised 166 undergraduate students. Factor analysis was applied to extract three indicators. FINDINGS: The MVQ showed divergent validity with the Positive Mental Health Questionnaire (p < .001) and convergent validity with the Mental Health Inventory including five items (p < .001). Reliability was verified through the assessment of internal consistency, evidencing positive outcomes (Cronbach's alpha = 0.81). PRACTICE IMPLICATIONS: The MVQ shows psychometric properties enabling its adaptation to clinical practice and research, essential to an effective screening of mental vulnerability. PMID- 27198976 TI - Elevated plasma levels of Th17-related cytokines are associated with increased risk of atrial fibrillation. AB - We performed a matched case-control study using a propensity score matching, to assess the association of Th17-related cytokines, including interleukin (IL) 17A (IL-17A), IL-17F, IL-21, IL-22 and IL-6, along with interferon-gamma (IFN-gamma), IL-10, IL-9, and IL-4, with the risk of AF. A total of 336 patients with AF were matched 1:1 with patients without AF. Plasma levels of cytokines were measured using Luminex xMAP assays. The plasma levels of all examined cytokines were significantly higher in AF patients than controls (P < 0.05), and these cytokines were highly correlated with each other (P < 0.01). A multivariate conditional logistic regression analysis showed that elevated plasma levels of IL-17A, IL 17F, IL-21, IL-22, IFN-gamma, IL-10, IL-9 and IL-6 were significantly associated with AF risk independently of potential confounders. There were no significant differences in plasma levels of examined cytokines between paroxysmal and chronic AF patients. IL-17A, IL-21, IL-10 and IL-6 levels were positively correlated with left atrial diameter; IL-17F level was negatively correlated with left ventricle ejection fraction among AF patients (P < 0.05). Elevated plasma levels of Th17 related cytokines were independently associated with increased an risk of AF; hence, Th17-related cytokines may be involved in the pathogenesis of AF. PMID- 27198978 TI - Progress in improving provincial plans for nutrition through targeted technical assistance and local advocacy in Vietnam. AB - Vietnam has been decentralizing nutrition planning to provinces, which could help with local relevance and accountability. Assessment in 2009 found a continuing top-down approach, limited human capacity, and difficulty in integrating multiple sectors. Alive and Thrive (A&T) provided targeted assistance and capacity building for 15 provincial plans for nutrition (PPNs). We aimed to (i) assess PPN content and quality improvements 2009-2014, and (ii) explain processes through which change occurred. Data consisted of interview-based assessments of provincial planning processes, annual PPN assessments, and tracking of A&T involvement. At endline, some provinces produced higher quality plans. Local planning skills improved, but capacity remained insufficient. Awareness of and support for nutrition improved, but some policy and legal environments were contradictory. Objectives were clearer, but use of data for planning remained inconsistent. Provinces became more proactive and creative, but remained constrained by slow approval processes and insufficient funding. Targeted assistance and local advocacy can improve decentralized planning, with success dependent on policy and programming contexts and ability to overcome constraints around capacity, investment, data use and remnants of centralized planning. We recommend strong engagement with planners at the national level to understand how to unblock major constraints; solutions must take into consideration the particular political, financial and administrative context. PMID- 27198977 TI - The influence of health system organizational structure and culture on integration of health services: the example of HIV service monitoring in South Africa. AB - Administrative integration of disease control programmes (DCPs) within the district health system has been a health sector reform priority in South Africa for two decades. The reforms entail district managers assuming authority for the planning and monitoring of DCPs in districts, with DCP managers providing specialist support. There has been little progress in achieving this, and a dearth of research exploring why. Using a case study of HIV programme monitoring and evaluation (M&E), this article explores whether South Africa's health system is configured to support administrative integration. The article draws on data from document reviews and interviews with 54 programme and district managers in two of nine provinces, exploring their respective roles in decision-making regarding HIV M&E system design and in using HIV data for monitoring uptake of HIV interventions in districts. Using Mintzberg's configurations framework, we describe three organizational parameters: (a) extent of centralization (whether district managers play a role in decisions regarding the design of the HIV M&E system); (b) key part of the organization (extent to which sub-national programme managers vs district managers play the central role in HIV monitoring in districts); and (c) coordination mechanisms used (whether highly formalized and rules-based or more output-based to promote agency). We find that the health system can be characterized as Mintzberg's machine bureaucracy. It is centralized and highly formalized with structures, management styles and practices that promote programme managers as lead role players in the monitoring of HIV interventions within districts. This undermines policy objectives of district managers assuming this leadership role. Our study enhances the understanding of organizational factors that may limit the success of administrative integration reforms and suggests interventions that may mitigate this. PMID- 27198979 TI - Recent trends in working with the private sector to improve basic healthcare: a review of evidence and interventions. AB - The private sector provides the majority of health care in Africa and Asia. A number of interventions have, for many years, applied different models of subsidy, support and engagement to address social and efficiency failures in private health care markets. We have conducted a review of these models, and the evidence in support of them, to better understand what interventions are currently common, and to what extent practice is based on evidence. Using established typologies, we examined five models of intervention with private markets for care: commodity social marketing, social franchising, contracting, accreditation and vouchers. We conducted a systematic review of both published and grey literature, identifying programmes large enough to be cited in publications, and studies of the listed intervention types. 343 studies were included in the review, including both published and grey literature. Three hundred and eighty programmes were identified, the earliest having begun operation in 1955. Commodity social marketing programmes were the most common intervention type, with 110 documented programmes operating for condoms alone at the highest period. Existing evidence shows that these models can improve access and utilization, and possibly quality, but for all programme types, the overall evidence base remains weak, with practice in private sector engagement consistently moving in advance of evidence. Future research should address key questions concerning the impact of interventions on the market as a whole, the distribution of benefits by socio-economic status, the potential for scale up and sustainability, cost-effectiveness compared to relevant alternatives and the risk of unintended consequences. Alongside better data, a stronger conceptual basis linking programme design and outcomes to context is also required. PMID- 27198980 TI - Sparking, supporting and steering change: grounding an accountability framework with viewpoints from Nigerian routine immunization and primary health care government officials. AB - Existing accountability efforts in Nigeria primarily serve as retrospective policing. To enable accountability to guide change prospectively and preemptively, we drew from a literature review to develop a framework that highlights mutually reinforcing dimensions of accountability in health systems along three counterbalancing axes. The axis of power sparks change by wielding 'sticks' that curb the potential abuse of power, but also by offering 'carrots' that motivate constructive agency. The axis of ability supports change by enabling service delivery actors with formal rules that appropriately expand their authority to act, but also the informal norms and inputs for improved performance. Last, the axis of justice orients the strategic direction of change, balancing political representation, community ownership and social equity, so that accountability measures are progressive, rather than being captured by self interests. We consulted Nigerian government officials to understand their viewpoints on accountability and mapped their responses to our evolving framework. All government officials (n = 36) participating in three zonal workshops on routine immunization filled out questionnaires that listed the top three opportunities and challenges to strengthening accountability. Thematically coded responses highlighted dimensions of accountability within the axes of ability and power: clarifying formal roles and responsibilities; transparency, data and monitoring systems; availability of skilled health personnel that are motivated and supervised; addressing informal norms and behaviours; and availability of inputs regarding funding and supplies. Other dimensions of accountability were mentioned but were not as critical from their viewpoints: managerial discretion; sanctions and enforcements; political influence and community engagement. Strikingly, almost no respondents mentioned social equity as being an important aspect of accountability, although a few mentioned broad development concerns that reflected community perspectives. Reframing accountability as a means of sparking, supporting and steering change can highlight different dimensions of health systems that need reform, particularly depending on the positionality of the viewpoints consulted. PMID- 27198981 TI - Using microfinance to facilitate household investment in sanitation in rural Cambodia. AB - Improved sanitation access is extremely low in rural Cambodia. Non-governmental organizations have helped build local supply side latrine markets to promote household latrine purchase and use, but households cite inability to pay as a key barrier to purchase. To examine the extent to which microfinance can be used to facilitate household investment in sanitation, we applied a two-pronged assessment: (1) to address the gap between interest in and use of microfinance, we conducted a pilot study to assess microfinance demand and feasibility of integration with a sanitation marketing program and (2) using a household survey (n = 935) at latrine sales events in two rural provinces, we assessed attitudes about microfinance and financing for sanitation. We found substantial stated intent to use a microfinance institution (MFI) loan to purchase a latrine (27%). Five percent of current owners used an MFI loan for latrine purchase. Credit officers attended 159 events, with 4761 individuals attending. Actual loan applications were low, with 4% of sales events attendees applying for a loan immediately following the event (mean = 1.7 loans per event). Ongoing coordination was challenging, requiring management commitment from the sanitation marketing program and commitment to social responsibility from the MFI. Given the importance of improving sanitation coverage and concomitant health impacts, linking functional sanitation markets to already operational finance markets has the potential to give individuals and households more financial flexibility. Further product research and better integration of private vendors and financing modalities are necessary to create a scalable microfinance option for sanitation markets. PMID- 27198983 TI - Anti-tumor activity of heat-killed Lactobacillus plantarum BF-LP284 on Meth-A tumor cells in BALB/c mice. AB - Probiotics exert numerous effects on human well-being. Here, heat-killed Lactobacillus plantarum BF-LP284 (H-Lp) was isolated as a potent immuno-modulator among 15 strains of lactobacilli in terms of TNF-alpha induction ability in peritoneal macrophages. In vitro TNF-alpha and IFN-gamma induction in Peyer's patch (PP) cells was higher when incubated with H-Lp than with live L. plantarum BF-LP284 (L-Lp). Suppression of syngeneic Meth-A tumors in a murine model by oral administration of H-Lp was also greater than that of L-Lp and of controls. H-Lp stimulated IFN-gamma production in spleen cells, which displayed inhibited tumor growth in Winn assays when treated with H-Lp. Moreover, H-Lp increased the ratio of CD3(+ )cells among peripheral blood mononuclear cells in Meth-A tumor-bearing mice, suggesting an H-Lp-mediated anti-tumor mechanism whereby immune cells that are activated by H-Lp in PP and acquire anti-tumor activity in the spleen migrate to tumor sites through lymphocyte homing to inhibit tumor growth. PMID- 27198985 TI - The Use of Azoles Containing Natural Products in Cancer Prevention and Treatment: An Overview. AB - BACKGROUND & OBJECTIVE: Cancer is one of the leading causes of death worldwide. In view of ever increasing number associated with cancer related death, there is an urgent need to find out a novel compound especially of natural origin (better efficacy, less or non-toxic and cost effective) that could serve against the treatment of all forms of cancer. Currently, available treatment options related to cancer have their certain limitations especially in the case of solid tumors. METHOD: In search of the natural anticancer compound, alkaloids, in general, have been exploited by the scientist working in this field of research. Among these alkaloids, azoles (secondary metabolite) have been significantly highlighted in literature because of their anticancer potential and better efficacy against various forms of cancer. RESULTS: Their mechanism of action includes induction in the cleavage of poly-ADP ribose polymerase (PARP), induction of caspase 3 and caspase 9, modulation of nuclear factor kappa B, damage to DNA, cell cycle arrest at G1 and G2/M stage, apoptosis and c-Myb inhibition. In the current article, we have tried to cover various azoles especially from oxazoles, thiazoles and carbazoles class that have been reported for their anticancer potential. CONCLUSION: Based on our article, we believe that, soon, the scientific community will come up with certain azole which will work against cancer at large rather than a specific type of cancer. PMID- 27198984 TI - Effect of PUFAs Oral Administration on the Amount of Apoptotic Caspases Enzymes in Gastric Cancer Patients Undergoing Chemotherapy. AB - OBJECTIVE: Gastric cancer is the fourth most common cancer and the second cause of death in the world. According to the studies, the gastric cancer is relatively sensitive to chemotherapy. The aim of this study was to investigate the association of oral administer PUFAs with Caspase enzymes in patients with gastric cancer under chemotherapy. METHODS: This study was a Clinical Trial in which the target group consisted of the patients recognized with gastric cancer for the first time and cured under chemotherapy. Thirty-four patients were selected and categorized randomly into two groups. The case group included the patients taking PUFAs along with chemotherapeutic agent. In these patients, chemotherapy started with Cis-Platin plus PUFAs supplement in the scale of 3600 mg daily and in three courses. In control group, the individuals were under the same chemotherapy protocol without PUFAs. Biopsy samples from tumor were taken from the patients before and after chemotherapy. Levels of mRNA and protein expression of caspase 3, 8, 9 were measured in biopsy samples by Real-Time PCR and Frozen Section methods. The levels of apoptosis were determined using DNA damage colorimetric assay. RESULTS: In the case group, caspase 3 showed a significant increase in both gene and protein expression levels after administration of PUFAs supplement in comparison with those of the control group (p=0.006 for gene, p=0.001 for protein). PUFAs induced caspase-9 gene expression level in these patients (p<0.0001). Caspase-9 protein level also revealed a marked elevation when PUFAs were administered along with chemotherapeutic agent (p<0.0001). DNA damage in gastric tissue from the patients under PUFAs treatment plus Cis-Platin was significantly higher than that of control group (p=0.003). PUFAs showed no significant changes in caspase-8 both at the gene and protein levels in the patients. CONCLUSION: According to the results of present study, it appears that oral administration of PUFAs can elevate the efficacy of chemotherapy agent in individuals' mitochondria-dependent apoptosis. As PUFAs enhances caspase-3 and 9 genes expression levels, which is an important induce the mitochondrial dependent apoptosis process. The study was registered in Iran clinical trials registry center under No. IRCT2014031016922N1. PMID- 27198986 TI - The Role of Tumor Associated Macrophages in the Tumor Microenvironment: Mechanism and Functions. AB - During tumor progression, several types of inflammatory cells are recruited into the tumor site, where they participate in tumor-associated inflammation, such as fibroblasts, granulocytes, lymphocytes and macrophages. Macrophages infiltrating into the tumor microenvironment are termed tumorassociated macrophages (TAMs). In response to multiple stimuli, macrophages undergo recruitment and polarization, and play an important role in further tumor development. In this article, we present a review of the mechanism of macrophage' recruitment, and the role that TAMs play in promoting immunosuppression, tumor progress and metastasis, as well as chemoresistance and future therapeutic strategies. PMID- 27198987 TI - The cytotoxic effect of GW843682X on nasopharyngeal carcinoma. AB - BACKGROUND: GW843682X is a publicly available anti-cancer compound by inhibiting Polo-like kinase. Previous studies revealed that GW843682X inhibited the proliferation of various tumor cell lines. In this study, the cytotoxic effect of GW843682X was investigated on cell proliferation, cell cycle and apoptosis of nasopharyngeal carcinoma 5-8F cells. METHODS: Cell morphological changes were observed by inverted microscopy. Cell proliferation was tested by CCK8 assay. Cell cycle arrest and apoptosis were tested by flow cytometry. The mechanism of apoptosis was investigated by RT-PCR to determine the mRNA expression of IAP-1, IAP-2, XIAP, and survivin. RESULTS: GW843682X resulted in remarkable cell morphological changes with the increase of drug concentrations. CCK8 assay revealed that GW843682X inhibited the proliferation and induced apoptosis of 5-8F cells in a dose-dependent manner (IC50=62.5-125nmol/L). After treating 5-8F cells with different doses of GW843682X for 12 h, G2/M phase cells significantly increased while G0/G1 phase cells remarkably decreased. Interestingly, GW843682X significantly inhibited the mRNA expression of IAP-1 and survivin, which function as key regulators of mitosis and programmed cell death, and is overexpressed in many tumor types. The mechanism of cytotoxic effect is partially due to the inhibition of IAP gene expression. CONCLUSION: These findings indicated that GW843682X exhibited remarkable cytotoxic effects on nasopharyngeal carcinoma 5-8F cells by down-regulating IAP gene expression, suggesting that GW843682X may become a novel therapeutic agent for nasopharyngeal carcinoma. PMID- 27198988 TI - In Vivo Inhibition of Proteasome Activity and Tumour Growth by Murraya koenigii Leaf Extract in Breast Cancer Xenografts and by Its Active Flavonoids in Breast Cancer Cells. AB - Inhibition of the 26S proteasome is an attractive approach for anticancer therapy. Proteasome inhibitors are known to selectively target cancer cells and make them more sensitive to chemotherapeutic agents. Murraya koenigii is a medicinally important herb of Asian origin and a rich source of bioactive compounds such as flavonoids and alkaloids. In the present study, we investigated the proteasome inhibitory and apoptotic effect of M. koenigii leaf extract in vivo in a xenograft tumor mouse model, and also assessed the toxicity if any in normal mice. M. koenigii extract did not lead to any toxicity in mice. Analysis of extract revealed the presence of flavonoid compounds which act as proteasome inhibitors. Quercetin treatment led to the decrease in the cell viability and arrest of cells in G2/M phase. Quercetin, Apigenin, Kaempferol and Rutin; flavonoids present in the leaf extract, dose-dependently inhibited the endogenous 26S proteasome activity in MDA-MB-231 cells. Reduction in tumor growth was associated with a decrease in proteasomal enzyme activities in the treated groups. Increased caspase-3 activity and TUNEL-positive cells indicated enhanced apoptosis with Murraya leaf extract treatment. Decreased expression of angiogenic and anti-apoptotic gene markers is indicative of inhibition of angiogenesis and promotion of apoptosis in the leaf extract treated tumors. PMID- 27198989 TI - Epithelial-to-Mesenchymal Transition in Paclitaxel-Resistant Ovarian Cancer Cells Is Downregulated by Luteolin. AB - Ovarian cancer (OVCA) is the deadliest of all gynecological cancers which is attributed to late presentation, persistence, and development of chemoresistance. The objectives were to evaluate the association between OVCA paclitaxel resistance and epithelial-to-mesenchymal transition (EMT) and to determine the capability of luteolin to chemosensitize OVCA cells. X10 and X22 cells were 11.8 25.3-fold and 7.8-8.6-fold resistant to paclitaxel than 1AP cells. X10 and X22 cells exhibited a mesenchymal phenotype, while 1AP has an epithelial characteristics. Furthermore, the expression of the epithelial marker E-cadherin was downregulated, while mesenchymal markers Vimentin and N-cadherin were upregulated in X10 and X22 cells when compared to 1AP cells. Transcription factors Snail, Slug, and Twist1 were upregulated in X10 cells, while Twist1 was highly expressed in X22 cells. Luteolin treatment caused cytotoxicity being most potent to X10 OVCA cells. Treatment of non-cytotoxic dose of luteolin at 15.625 MUM chemosensitized X10 and X22 OVCA cells to paclitaxel as evidenced by reduced ED50 values from 11.8 to 0.2 MUM and 8.6 to 3.6 MUM for X10 and X22 cells, respectively. Moreover, luteolin treatment led to a more epithelial phenotype of X10 and X22 cells and modification of EMT markers indicating reversal of EMT. The mechanism involved is through reduction of phosphorylation of FAK and ERK leading to reduced nuclear translocation of p65. Our results highlight the significance of EMT in OVCA resistance to paclitaxel and warrant the investigation of luteolin as a potential therapeutic agent in chemoresistant OVCA. J. Cell. Physiol. 232: 391-401, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27198990 TI - Small molecule recognition of mephedrone using an anthracene molecular clip. AB - An anthracene molecular probe has been synthesised and shown to target mephedrone, a stimulant drug from the cathinone class of new psychoactive substances (NPS). A protocol has been developed to detect mephedrone via the probe using NMR spectroscopy in a simulated street sample containing two of the most common cutting agents, benzocaine and caffeine. PMID- 27198991 TI - The effects of emotion priming on visual search in socially anxious adults. AB - This study examined the effects of emotion priming on visual search in participants characterised for different levels of social anxiety. Participants were primed with five facial emotions (angry, fear, happy, neutral, and surprised) and one scrambled face immediately prior to visual search trials involving finding a slanted coloured line amongst distractors, as reaction times and accuracy to target detection were recorded. Results suggest that for individuals low in social anxiety, being primed with an angry, surprised, or fearful face facilitated visual search compared to being primed with scrambled, neutral or happy faces. However, these same emotions degraded visual search in participants with high levels of social anxiety. This study expands on previous research on the impact of emotion on attention, finding that amongst socially anxious individuals, the effects of priming with threat extend beyond initial attention capture or disengagement, degrading later visual search. PMID- 27198982 TI - Retroviral DNA Integration. AB - The integration of a DNA copy of the viral RNA genome into host chromatin is the defining step of retroviral replication. This enzymatic process is catalyzed by the virus-encoded integrase protein, which is conserved among retroviruses and LTR-retrotransposons. Retroviral integration proceeds via two integrase activities: 3'-processing of the viral DNA ends, followed by the strand transfer of the processed ends into host cell chromosomal DNA. Herein we review the molecular mechanism of retroviral DNA integration, with an emphasis on reaction chemistries and architectures of the nucleoprotein complexes involved. We additionally discuss the latest advances on anti-integrase drug development for the treatment of AIDS and the utility of integrating retroviral vectors in gene therapy applications. PMID- 27198992 TI - Tracking online poker problem gamblers with player account-based gambling data only. AB - The aim was to develop and validate an instrument to track online problem poker gamblers with player account-based gambling data (PABGD). We emailed an invitation to all active poker gamblers on the online gambling service provider Winamax. The 14,261 participants completed the Problem Gambling Severity Index (PGSI). PGSI served as a gold standard to track problem gamblers (i.e., PGSI >= 5). We used a stepwise logistic regression to build a predictive model of problem gambling with PABGD, and validated it. Of the sample 18% was composed of online poker problem gamblers. The risk factors of problem gambling included in the predictive model were being male, compulsive, younger than 28 years, making a total deposit > 0 euros, having a mean loss per gambling session > 1.7 euros, losing a total of > 45 euros in the last 30 days, having a total stake > 298 euros, having > 60 gambling sessions in the last 30 days, and multi-tabling. The tracking instrument had a sensitivity of 80%, and a specificity of 50%. The quality of the instrument was good. This study illustrates the feasibility of a method to develop and validate instruments to track online problem gamblers with PABGD only. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27198993 TI - The Pain Attitudes and Beliefs Scale for Physiotherapists: Dimensionality and Internal Consistency of the Norwegian Version. AB - BACKGROUND AND PURPOSE: The Pain Attitudes and Beliefs Scale for Physiotherapists (PABS-PT) is a self-administered instrument developed to assess the strength of two possible treatment orientations of physiotherapists towards the management of low back pain. The aim of this study was to translate the PABS-PT into Norwegian from the original 36-item Dutch version and to examine its dimensionality and internal consistency. METHODS: The Norwegian version was generated in a forward backward translation procedure. To examine construct validity, a cross-sectional web-based survey was conducted. A convenience sample of 3849 physiotherapists was invited to fill out the Norwegian PABS-PT, together with demographic and professional data. Only therapists who had been involved in back pain management for the last 6 months were included. Principal factor and Cronbach's alpha analyses were performed to determine the factor structure and internal consistency, respectively. RESULTS: The PABS-PT was successfully translated into Norwegian. Responses from 921 therapists were obtained (response rate 24.8%), and of these, 647 could be included in the factor analysis. Analysis revealed two factors, labelled 'biomedical' and 'biopsychosocial' treatment orientation, which confirmed the structure of the original Dutch version. Thirty-six items were reduced to 19, with 13 items loading on factor I and six items on factor II, explaining 18.1% and 7.1%, respectively, of the total variance. Cronbach's alpha of the biomedical sub-scale was 0.79 and 0.57 for the bio-psychosocial sub-scale. CONCLUSION: The Norwegian version of the PABS-PT appears to be equivalent to the original Dutch version, showing a similar structure and internal consistency. The two factors accounted for low explained variance, which may be indicative for problematic construct validity. Psychometric properties and usefulness will be further examined. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27198994 TI - Parental understanding and self-blame following sudden infant death: a mixed methods study of bereaved parents' and professionals' experiences. AB - OBJECTIVES: Improvements in our understanding of the role of modifiable risk factors for sudden infant death syndrome (SIDS) mean that previous reassurance to parents that these deaths were unpreventable may no longer be appropriate. This study aimed to learn of bereaved parents' and healthcare professionals' experiences of understanding causes of death following detailed sudden unexpected death in infancy (SUDI) investigations. The research questions were: How do bereaved parents understand the cause of death and risk factors identified during detailed investigation following a sudden unexpected infant death? What is the association between bereaved parents' mental health and this understanding? What are healthcare professionals' experiences of sharing such information with families? DESIGN: This was a mixed-methods study using a Framework Approach. SETTING: Specialist paediatric services. PARTICIPANTS: Bereaved parents were recruited following detailed multiagency SUDI investigations; 21/113 eligible families and 27 professionals participated giving theoretical saturation of data. DATA COLLECTION: We analysed case records from all agencies, interviewed professionals and invited parents to complete the Hospital Anxiety and Depression Scale (HADS) and questionnaires or in-depth interviews. RESULTS: Nearly all bereaved parents were able to understand the cause of death and several SIDS parents had a good understanding of the relevant modifiable risk factors even when these related directly to their actions. Paediatricians worried that discussing risk factors with parents would result in parental self-blame and some deliberately avoided these discussions. Over half the families did not mention blame or blamed no one. The cause of death of the infants of these families varied. 3/21 mothers expressed overwhelming feelings of self-blame and had clinically significant scores on HADS. CONCLUSIONS: Bereaved parents want detailed information about their child's death. Our study suggests parents want health professionals to explain the role of risk factors in SIDS. We found no evidence that sharing this information is a direct cause of parental self-blame. PMID- 27198995 TI - Renoprotection in acute kidney injury - quoi de neuf ? PMID- 27198996 TI - Nipple-Sparing Mastectomy with Immediate Breast Reconstruction in Breast Cancer Patients with Tumour-Nipple Distance Less Than 2.0 cm: The Jury is Still Out. PMID- 27198997 TI - The Influence of the Appendiceal Base Diameter on Appendix Stump Closure in Laparoscopic Appendectomy. AB - BACKGROUND: Closure of the appendiceal stump is the most critical part of laparoscopic appendectomy. Establishing the average diameter of the inflamed appendix, and forming the appropriate size of clip, endoloop or stapler length, would make this critical phase of laparoscopic appendectomy easier. METHODS: One hundred and fifty consecutive patients, with the diagnosis of acute appendicitis, were included in this study and divided into three groups according to the histological verification of the status of the infection, as follows: phlegmonous, gangrenous and perforated forms of acute appendicitis. The external diameter of the appendiceal base was measured, and the widest part of the appendix with the mesoappendix and the tip, with the help of Vernier callipers, and the measurement was expressed in millimetres. RESULTS: The average size of the appendiceal base in the phlegmonous form was 10.29 +/- 3.13, in the gangrenous form 12.41 +/- 3.56, and in the perforated form 12.42 +/- 3.64. The maximal size of base was observed in the perforated form, 23.13 mm. The dimensions of the appendiceal base, the central part and the tip in the phlegmonous form were statistically significantly smaller than in the gangrenous and perforated forms of acute appendicitis. The size of the appendix did not differ statistically significantly in the gangrenous and perforated forms of acute appendicitis. CONCLUSION: In view of the price, the size of the opening, radiological advantage and biocompatibility, the Hem-o-lok clip is the most effective, although its internal diameter should be increased. The DS clip is also effective, but the size of the opening sometimes makes application difficult, and possibly increasing the length of the legs and the opening would make this clip ideal. Staplers have the best characteristics, but their price means they are an option only for forms where it is not possible to close the stump using other methods. PMID- 27198998 TI - Association Between Cholecystectomy and Nonalcoholic Fatty Liver Disease: A Meta analysis: Reply. PMID- 27199001 TI - Lymphocyte to monocyte ratio and prognostic nutritional index predict survival outcomes of hepatitis B virus-associated hepatocellular carcinoma patients after curative hepatectomy. AB - INTRODUCTION: Lymphocytes are an integral part of lymphocyte to monocyte ratio (LMR) and prognostic nutritional index (PNI). Both LMR and PNI which reflect body's inflammatory and nutritional status can be obtained from routine blood and biochemical test conveniently. Little evidence concerning the prognostic value of LMR and PNI in hepatocellular carcinoma (HCC) patients has been published. This study aimed to investigate the prognostic value of LMR and PNI in hepatitis B virals (HBV)-associated HCC patients who underwent curative hepatectomy. METHODS: Between January 2008 and June 2013, 450 surgically treated HCC patients were retrospectively analyzed. Clinicopathological parameters, LMR and PNI were collected and compared. The multivariate analysis was performed to indentify independent prognostic factors. Overall survival (OS) and recurrence-free survival (RFS) rates were also compared. RESULTS: Tumor size, vascular invasion, alpha fetoprotein level, LMR and PNI were independent prognostic factors for OS. Tumor number, tumor size, vascular invasion, LMR and PNI were independent prognostic factors for RFS. Either a high LMR or PNI could predict favorable OS and RFS in surgically treated HCC patients and vice versa. CONCLUSIONS: Both LMR and PNI were significant independent predictors that can predict survival outcomes in HBV-associated HCC patients who received curative hepatectomy. J. Surg. Oncol. 2016;114:202-210. (c) 2016 Wiley Periodicals, Inc. PMID- 27199000 TI - Antibiotics Versus Appendicectomy for the Treatment of Uncomplicated Acute Appendicitis: An Updated Meta-Analysis of Randomised Controlled Trials. AB - BACKGROUND: Uncomplicated acute appendicitis has been managed traditionally by early appendicectomy. However, recently, there has been increasing interest in the potential for primary treatment with antibiotics, with studies finding this to be associated with fewer complications than appendicectomy. The aim of this study was to compare outcomes of antibiotic therapy with appendicectomy for uncomplicated acute appendicitis. METHOD: This meta-analysis of randomised controlled trials included adult patients presenting with uncomplicated acute appendicitis treated with antibiotics or appendicectomy. The primary outcome measure was complications. Secondary outcomes included treatment efficacy, hospital length of stay (LOS), readmission rate and incidence of complicated appendicitis. RESULTS: Five randomised controlled trials with a total of 1430 participants (727 undergoing antibiotic therapy and 703 undergoing appendicectomy) were included. There was a 39 % risk reduction in overall complication rates in those treated with antibiotics compared with those undergoing appendicectomy (RR 0.61, 95 % CI 0.44-0.83, p = 0.002). There was no significant difference in hospital LOS (mean difference 0.25 days, 95 % CI -0.05 to 0.56, p = 0.10). In the antibiotic cohort, 123 of 587 patients initially treated successfully with antibiotics were readmitted with symptoms suspicious of recurrent appendicitis. The incidence of complicated appendicitis was not increased in patients who underwent appendicectomy after "failed" antibiotic treatment (10.8 %) versus those who underwent primary appendicectomy (17.9 %). CONCLUSION: Increasing evidence supports the primary treatment of acute uncomplicated appendicitis with antibiotics, in terms of complications, hospital LOS and risk of complicated appendicitis. Antibiotics should be prescribed once a diagnosis of acute appendicitis is made or considered. PMID- 27198999 TI - Distal Pancreatectomy with En Bloc Resection of the Celiac Axis with Preservation or Reconstruction of the Left Gastric Artery in Patients with Pancreatic Body Cancer. AB - BACKGROUND: A distal pancreatectomy with en bloc celiac axis resection (DP-CAR) is indicated for left-sided locally advanced pancreatic ductal adenocarcinoma. However, ischemic complication resulting from the sacrifice of the common hepatic artery and left gastric artery (LGA) remain problematic. The aim of this study was to analyze the feasibility of DP-CAR with preservation or reconstruction of the left gastric artery. METHOD: Between April 2011 and December 2014, we treated 17 cases using DP-CAR with preservation or reconstruction of the LGA. If the tumor had involved the LGA, the LGA was dissected and reconstructed using the middle colic artery. We retrospectively analyzed the feasibility of this procedure. RESULTS: Among 17 consecutive patients who underwent DP-CAR, the LGA was preserved in 13 patients and reconstructed in four patients. Major postoperative complications were observed in seven cases (41 %). A pancreatic fistula (grade B/C) or delayed gastric emptying (grade B/C) occurred in 7 (41 %) and 2 (12 %) cases, respectively. The overall R0 resection rate was 94 % (16/17). Eleven cases developed recurrences (liver, n = 4; lymph nodes, n = 2; peritoneal dissemination, n = 2; lung, n = 2; local recurrence, n = 1). The overall 1- and 3 year postoperative survival rates were 74 and 45 %, respectively. CONCLUSIONS: Our preliminary data showed that DP-CAR with preservation or reconstruction of the LGA is a safe and feasible approach, and that this procedure may reduce the risk of ischemic complications. PMID- 27199003 TI - Relationship between retinal distance and object field angles for finite schematic eyes. AB - AIM: Retinal anatomical studies have used the Drasdo & Fowler three-refracting surface schematic eye to convert between retinal distances and object field angles. We compared its performance at this task with those of more sophisticated four-refracting surface schematic eyes. METHOD: Raytracing was performed for Drasdo & Fowler, Lotmar, Navarro, Liou & Brennan, Kooijman and Atchison schematic eyes, and some of their variants. RESULTS: The Drasdo & Fowler eye gives a greater rate of change of object field angle with retinal distance at the retinal centre of about 5% than the other schematic eyes. This rate of change also increases much more quickly into the peripheral retina for the Drasdo & Fowler eye than for the other eyes. The reason for these differences is only that the Drasdo & Fowler eye is shorter than the other eyes. The relationship between retinal distance and visual field angle appears robust to changes in retinal radius of curvature when the retina is spherical. The retinal asphericity of Kooijman and Atchison eyes appears to play a role beyond 14 mm (~50 degrees ). CONCLUSION: Changing the length of the Drasdo & Fowler eye, to match those of the four-refracting surface schematic eyes, gives similar relationships between retinal distance and object field angle up to a retinal distance of approximately 14 mm (~50 degrees ). The relationship will change with refractive error as this is related to axial length and to retinal shape, and this should be taken into consideration for accurate conversions. For distances and angles beyond 14 mm and ~50 degrees , retinal shape should be taken into account. PMID- 27199002 TI - Electrical stimulation influences chronic intermittent hypoxia-hypercapnia induction of muscle fibre transformation by regulating the microRNA/Sox6 pathway. AB - Chronic obstructive pulmonary disease can cause muscle fibre transformation due to chronic intermittent hypoxia-hypercapnia (CIHH). Studies have shown that high expression of Sox6 in muscle could suppress type-I fibres through downregulating the PPARbeta (peroxisome proliferator-activated receptor beta)/ERRgamma (oestrogen-related receptor gamma)/microRNA pathway. However, whether this pathway is involved in CIHH-induced muscle fibre transformation is unknown. Electrical stimulation (ES) is an effective approach to ameliorate muscle dysfunction. Here, we explored the effects of ES on CIHH-induced muscle fibre transformation and the microRNA/Sox6 pathway. After CIHH exposure, both the soleus (SOL) and gastrocnemius (GC) muscles showed decreased type-I fibres. The PPARbeta/ERRgamma/mir-499&208b (PEM, for GC) and PPARbeta/mir-499&208b (PM, for SOL) signalling cascades were suppressed, followed by elevated Sox6 expression. Low frequency electrical stimulation (LFES) activated the PEM/PM pathway and enhanced type-I fibre numbers through suppressing Sox6 in SOL and GC. High frequency electrical stimulation (HFES) promoted type-I fibre expression through activating the PEM pathway in GC. Although PPARbeta expression and type-I fibres were suppressed in SOL after HFES, no significant change was found in mir 499&208b/Sox6 expression. These results suggest that the microRNA/Sox6 pathway is disturbed after CIHH. Both low and high frequency electrical stimulations induce muscle fibre transformation partly through regulating the microRNA/Sox6 pathway. PMID- 27199004 TI - New contract will "strengthen morale" of junior doctors, says health secretary. PMID- 27199005 TI - Extruded whole grain diets based on brown, soaked and germinated rice. Effects on cecum health, calcium absorption and bone parameters of growing Wistar rats. Part I. AB - The influence of diets with whole rice processed ingredients on cecum health, calcium absorption and bone parameters was studied using an animal model. Thirty two male Wistar rats were fed with Control (C), extruded Brown rice (B), extruded Soaked whole rice (S) and extruded Germinated whole rice (G) diets for 60 days. The cecum weight, cecal content pH, cecal sIgA content, and beta-glucosidase and beta-glucuronidase activities were determined. Calcium apparent absorption, total bone mineral content and density and right femur parameters (ashes, organic content, calcium and P) were evaluated. The results showed that animals fed with whole grain diets have lower food intake in comparison with the C diet, and decreased cecal content pH (7.06 vs. 6.33) and beta-glucosidase activity (1.66 vs. 0.21 MUmol p-nitrophenol g(-1) cc h(-1)). Even though calcium apparent absorption was not different among treatments (~70%), none of the whole grain diets improved calcium related bone parameters over the control fed rats (cellulose as dietary fibre). PMID- 27199006 TI - Atlas of Gynecologic Cytopathology with Histopathologic Correlations. PMID- 27199008 TI - The status of the species Moorella thermoautotrophica Wiegel et al. 1981. Request for an Opinion. AB - Based on the results of DNA-DNA hybridization and 16S rRNA gene sequence analyses, it was ascertained that the type strain of Moorella thermoautotrophica does not exist in any established culture collection or with the authors who originally described this species. Therefore, this species cannot be included in any further scientific studies. It is proposed that the Judicial Commission place the name Moorella thermoautotrophica on the list of rejected names if a suitable type strain is not found or a neotype is not proposed within two years following the publication of this Request for an Opinion. PMID- 27199009 TI - Separating hydrogen and oxygen evolution in alkaline water electrolysis using nickel hydroxide. AB - Low-cost alkaline water electrolysis has been considered a sustainable approach to producing hydrogen using renewable energy inputs, but preventing hydrogen/oxygen mixing and efficiently using the instable renewable energy are challenging. Here, using nickel hydroxide as a redox mediator, we decouple the hydrogen and oxygen production in alkaline water electrolysis, which overcomes the gas-mixing issue and may increase the use of renewable energy. In this architecture, the hydrogen production occurs at the cathode by water reduction, and the anodic Ni(OH)2 is simultaneously oxidized into NiOOH. The subsequent oxygen production involves a cathodic NiOOH reduction (NiOOH->Ni(OH)2) and an anodic OH(-) oxidization. Alternatively, the NiOOH formed during hydrogen production can be coupled with a zinc anode to form a NiOOH-Zn battery, and its discharge product (that is, Ni(OH)2) can be used to produce hydrogen again. This architecture brings a potential solution to facilitate renewables-to-hydrogen conversion. PMID- 27199007 TI - Embryonic development and inviability phenotype of chicken-Japanese quail F1 hybrids. AB - Interspecific hybrid incompatibility, including inviability and sterility, is important in speciation; however, its genetic basis remains largely unknown in vertebrates. Crosses between male chickens and female Japanese quails using artificial insemination can generate intergeneric hybrids; however, the hatching rate is low, and hatched hybrids are only sterile males. Hybrid development is arrested frequently during the early embryonic stages, and the sex ratio of living embryos is male-biased. However, the development and sex ratio of hybrid embryos have not been comprehensively analyzed. In the present study, we observed delayed embryonic development of chicken-quail hybrids during the early stage, compared with that of chickens and quails. The survival rate of hybrids decreased markedly during the blastoderm-to-pre-circulation stage and then decreased gradually through the subsequent stages. Hybrid females were observed at more than 10 d of incubation; however, the sex ratio of hybrids became male-biased from 10 d of incubation. Severely malformed embryos were observed frequently in hybrids. These results suggest that developmental arrest occurs at various stages in hybrid embryos, including a sexually non-biased arrest during the early stage and a female-biased arrest during the late stage. We discuss the genetic basis for hybrid inviability and its sex bias. PMID- 27199010 TI - What Is the Optimal Setting for a Continuous-Flow Left Ventricular Assist Device in Severe Mitral Regurgitation? AB - Excessive left ventricular (LV) volume unloading can affect right ventricular (RV) function by causing a leftward shift of the interventricular septum in patients with mitral regurgitation (MR) receiving left ventricular assist device (LVAD) support. Optimal settings for the LVAD should be chosen to appropriately control the MR without causing RV dysfunction. In this study, we assessed the utility of our electrocardiogram-synchronized rotational speed (RS) modulation system along with a continuous-flow LVAD in a goat model of MR. We implanted EVAHEART devices after left thoracotomy in six adult goats weighing 66.4 +/- 10.7 kg. Severe MR was induced through inflation of a temporary inferior vena cava filter placed within the mitral valve. We evaluated total flow (TF; the sum of aortic flow and pump flow [PF]), RV fractional area change (RVFAC) calculated by echocardiography, left atrial pressure (LAP), LV end-diastolic pressure (LVEDP), LV end-diastolic volume (LVEDV), and LV stroke work (LVSW) with a bypass rate (PF divided by TF) of 100% under four conditions: circuit-clamp, continuous mode, co pulse mode (increased RS during systole), and counter-pulse mode (increased RS during diastole). TF tended to be higher in the counter-pulse mode. Moreover, RVFAC was significantly higher in the counter-pulse mode than in the co-pulse mode, whereas LAP was significantly lower in all driving modes than in the circuit-clamp condition. Furthermore, LVEDP, LVEDV, and LVSW were significantly lower in the counter-pulse mode than in the circuit-clamp condition. The counter pulse mode of our RS modulation system used with a continuous-flow LVAD may offer favorable control of MR while minimizing RV dysfunction. PMID- 27199011 TI - Transforming our settings: make it happen everywhere. PMID- 27199012 TI - International perspectives on healthy settings: critical reflections, innovations and new directions. PMID- 27199013 TI - The development and achievement of a healthy cities network in Taiwan: sharing leadership and partnership building. AB - The World Health Organization (WHO) Healthy Cities (HC) projects are the best known of the settings-based approaches to health promotion. They engage local governments in health development through a process of political commitment, institutional change, capacity-building, partnership-based planning and innovative projects. Many cities have promoted HC projects in Taiwan since 2002. In 2008, the Taiwan Alliance for Healthy Cities (TAHC) was launched to assist local governments in effectively establishing, operating and promoting HC projects. In this article, we share our experiences of establishing a platform and network to promote the HC program in Taiwan. Based on individual city profiles and governance in Taiwan, the TAHC developed a well-organized framework and model to encourage strong leadership in local governments and to promote participation and engagement in their communities. In the last 6 years, leaders from Taiwan's local governments in HC networks have integrated the HC concepts into their governance models, actively engaging and combining various resources with practical expertise and private sectors. The network of health in Taiwan allows each city to develop its unique perspective on the HC projects. Using this method, not only local government meets its needs, but also increases governance efficiency and effectiveness, resulting in the promotion of its citizens' overall sustainable urban health development. This HC network in Taiwan has partnerships with government and non-governmental organizations (NGOs), with academic support and citizen involvement, a dynamic data collection system and demonstrated leadership in the sharing of information in the Asian region. PMID- 27199015 TI - Advances in health promotion in Asia-Pacific: promoting health through hospitals. AB - Since 1990, the WHO Health Promoting Hospital (HPH) movement has tried to facilitate and support hospitals to assume a core responsibility in health promotion. The Taiwan HPH Network was established in December 2006, and became the largest HPH network in the world in 2013. Compared to Europe where the HPH has been more established, the pace of HPH development has been much more rapid. This rapid development provides an inspiring example for research and health promotion practice. Systematic data and empirical information have been collected about HPH in Taiwan, allowing for research to be published about the achievements of the HPH movement. This paper provides an overview of the existing literature on current progress of the HPH project according to the four main perspectives of the WHO-HPH movement: promoting the health of patients, promoting the health of staff, changing the organization to a health-promoting setting, and promoting the health of the community in the catchment area of the hospital. The assessment can serve as a stepping stone in understanding current HPH development in Taiwan and as a reference for future research. PMID- 27199014 TI - Health-promoting educational settings in Taiwan: development and evaluation of the Health-Promoting School Accreditation System. AB - INTRODUCTION: The Taiwan Ministry of Health and Welfare and Ministry of Education launched the Health-Promoting School (HPS) program in 2002. One of the most significant barriers to evaluating HPS is the absence of adequate instruments. The main aim of this study is to develop the Taiwan Health-Promoting School Accreditation System (HPSAS) framework and then evaluate its accreditation effectiveness. METHODS: The HPSAS accreditation standards were derived mainly from the World Health Organization (WHO) publication, WHO Health Promoting Schools: A Framework for Action in 2008 and the Taiwan School Health Act. Delphi technique and pilot test were used to confirm the availability and acceptability of the standards and procedures for HPSAS in 2011. After that, two rounds of school evaluations were completed in 2012 (214 participant schools) and 2014 (182 participant schools). The accreditation operation process included documentary reviews, national and international accredited commissioners conducted on-site visits. Descriptive analyses were used to indicate HPS award level distribution. RESULTS: The study established six key HPSAS standards. Each standard had at least two components; overall, there were 21 components and 47 scoring elements. Of the participating schools evaluated in 2012, four were at the gold, 14 silver, and 120 bronze levels, compared with five, 20, and 31, respectively, of schools evaluated in 2014. The study showed that schools at different award levels had different full-score rates in six standards. The schools at the gold level performed exceptionally well. The worst performance among the six standards at each award level was in the skill-based health curriculum. CONCLUSION: The HPSAS is an objective instrument used to evaluate the process and outcomes of the HPS program. In the future, combinations of different types of data (e.g. students' health behaviors, school climate, or teachers' health-teaching innovations) will enable further validation of the HPS effectiveness. PMID- 27199016 TI - Following the trend for a comprehensive healthy workplace in Taiwan. AB - To promote workers' health and boost corporate productivity and national competitiveness, workplace health promotion is an international trend and a vital part of national policies. Prior to 2000, Taiwan's workplace issues focused on industrial hygiene and safety improvements. Since 2003, the Health Promotion Administration (HPA) at the Ministry of Health and Welfare has established coaching centers for workplace health promotion and dispatched trained experts for teaching health promotion skills; including promoting the tobacco control program, preventing important chronic diseases, driving comprehensive programs, advocating workplace health promotion with the Ministry of Labor, establishing certification mechanisms for workplace health promotion, recognizing outstanding health-promoting workplaces, and conducting a nationwide survey for monitoring the practices of healthy behaviors and health conditions of workers. Through 2014, 12,439 workplaces have been accredited.Since 2003, the efforts of the HPA in workplace health promotion projects has shifted society's focus on workplace health from occupational diseases and injury prevention to workplace health promotion, resulting in the revision of the Occupational Safety and Health Act in 2013 by the Ministry of Labor to detail employers' responsibilities in protecting and promoting employees' health and well-being. PMID- 27199017 TI - Implementing the Health Promoting University approach in culturally different contexts: a systematic review. AB - INTRODUCTION: Universities represent a valuable opportunity to promote health and well-being. Based on the setting approach, the Health Promoting Universities concept has been developed in different countries and contexts. However, the implementation process remains poorly documented. This systematic review aims to describe how universities have implemented the Health Promoting University concept in different cultural contexts. METHODS: Pubmed, Medline, Lilacs and Scielo were searched for articles on Health Promoting Universities, published between 1995 and 2015. Studies detailing the implementation of a Health Promoting University approach were included. Selected articles were content analysed paying attention to: (a) the definition of a Health Promoting University; (b) priority areas of action; (c) items of work; (d) coordination of the project; (e) evaluation; and (f) adaptation to the cultural context. RESULTS: Twelve studies were identified for in-depth analysis. Of those, three were theoretical papers, and nine were intervention studies. The programmes described in the selected studies are mostly based on the guidelines of the Edmonton Charter. They incorporated the main areas of action and items of works proposed by the Health Promoting University framework. The implementation of healthy policies and incorporation of health promotion in the curriculum are remaining challenges. Strategies to facilitate adaptation to context include: stakeholder participation in planning and implementation, adaptation of educational material and analysis of needs. CONCLUSIONS: The review suggests that most of the universities work towards similar goals, relying on the Health Promoting University framework, yet that the way in which initiatives are implemented depends on the context. PMID- 27199018 TI - Healthy universities: an example of a whole-system health-promoting setting. AB - The health-promoting settings approach is well established in health promotion, with organisational settings being understood as complex systems able to support human wellbeing and flourishing. Despite the reach and evident importance of higher education as a sector, 'healthy universities' has not received high-level international leadership comparable to many other settings programmes. This study explores how the concept of a healthy university is operationalised in two case study universities. Data collection methods included documentary analysis, observation field notes and semi-structured interviews with staff and students. Staff and students understood the characteristics of a healthy university to pertain to management processes relating to communication and to a respectful organisational ethos. Enhancers of health and wellbeing were feeling valued, being listened to, having skilled and supportive line managers and having a positive physical environment. Inhibitors of health and wellbeing were having a sense of powerlessness and a lack of care and concern. The concept of the healthy university has been slow to be adopted in contrast to initiatives such as healthy schools. In addition to challenges relating to lack of theorisation, paucity of evidence and difficulties in capturing the added value of whole-system working, this study suggests that this may be due to both their complex organisational structure and the diverse goals of higher education, which do not automatically privilege health and wellbeing. It also points to the need for a whole-university approach that pays attention to the complex interactions and interconnections between component parts and highlights how the organisation can function effectively as a social system. PMID- 27199019 TI - Health-promoting prisons: theory to practice. AB - As a setting, prisons offer a unique opportunity to invest in the health of disadvantaged and marginalised populations and address health inequalities and social exclusion - thereby achieving sustainable improvements in well-being for offenders and their families and in turn, helping to reduce rates of re offending. This article draws on English and French experiences and doctoral research to advocate a shift from a pathogenic model towards a salutogenic model of health as a helpful way to address inequalities and thus, by promoting joined up working across justice and wider systems, impact positively beyond 'health' for the effective resettlement of prisoners. The paper utilises examples from horticulture to further argue the powerful role of nature in the prison setting in mediating aspects of culture particularly relating to processes of socialisation. Critical success lies in bridging across systems and a commitment to joined-up working at all levels across and beyond prison. PMID- 27199020 TI - Piecing the puzzle together: case studies of international research in health promoting sports clubs. AB - This paper seeks to review the current international health-promoting sports club (HPSC) research, drawing together findings based on case studies from various countries to illustrate the status of HPSCs. In addition, future challenges for HPSC research and implementation are considered. The review includes six case studies from five countries. In summary, there are two major research themes in this area, namely 'research into HPSC activity' and 'research into HPSC networks'. The first theme investigates the extent to which sports clubs and/or national sports organisations invest in health promotion (HP) - both in policy and practice. The latter theme is driven by an intention to widen the scope of HPSCs to reach novel internal actors, like parents, siblings, etc., and/or external non-sporting bodies, like communities, schools, etc. The future challenges for HPSC research require a better understanding of the motives, barriers and capacities of sports clubs and coaches. Sports organisations, clubs and coaches generally support the intent of the HPSC concept, but even with the best evidence- or theory-based HP programmes/guidelines/standards, nothing will happen in practice if the nature and capacities of sports clubs are not better acknowledged. Therefore, a call for embracing implementation science is finally made to enhance implementation. PMID- 27199021 TI - The East Asian age-friendly cities promotion - Taiwan's experience and the need for an oriental paradigm. AB - It is the consensus that the rapid increase of the ageing population has become a global phenomenon. In 2007, the World Health Organization (WHO) advanced a handbook called Global Age-friendly Cities: A Guide The core concept of the age friendly cities (AFC) movement is 'active ageing'. Taiwan became one of the few Asian countries that initially responded to the WHO AFC movement in 2010. Following the guidance set by the WHO, Taiwan began its promotion at a national level, and with local authorities. However, during the advocacy process, the fundamental differences between Eastern and Western cultures in terms of family values and deep-rooted respect for the elderly have raised an awareness of the need for an oriental paradigm. This paper identifies three key elements for AFC promotion in East Asian countries based on an analysis of Taiwan's experience: during needs assessment take collectivism into consideration, during action plans at the community level community leaders' views will be more important (particularism), and when promoting AFC at the institutional level a top-down approach will be more acceptable (high power distance concept). PMID- 27199022 TI - Healthy Cities and the Transition movement: converging towards ecological well being? AB - This commentary identifies similarities, differences and opportunities for synergy and mutual learning between the Healthy Cities and the Transition movements. We outline what we consider to be the 'pressing issues' facing humanity and the planet in the early 21(st) century; consider the extent to which health promotion has engaged with and addressed these issues; compare Healthy Cities and the Transition movement; and conclude by suggesting possibilities for moving forward. PMID- 27199023 TI - Equity, sustainability and governance in urban settings. AB - In this commentary the urban setting is explored from the perspective of ecological sustainability and social equity. Urban-related issues are highlighted related to social inequality, deficits in urban infrastructures, behavior-related illnesses and risks, global ecological changes, and urban sprawl. Approaches to addressing these issues are described from the perspective of urban governance, urban planning and design, social determinants of health, health promotion, and personal and community empowerment. Examples of successful strategies are provided from Latin America, including using participatory instruments (assessments, evaluation, participatory budgeting, etc.), establishing intersectoral committees, increasing participation of civil society organizations, and developing virtual forums and networks to channel participatory and collaborative processes. A way forward is proposed, using the urban setting to show the imperative of creating intersectoral policies and programs that produce environments that are both healthy and sustainable. It will be important to include new forms of social participation and use social media to facilitate citizen decision-making and active participation of all sectors of society, especially excluded groups. PMID- 27199025 TI - Perspectives internationales sur les lieux de vie favorables a la sante : reflexions critiques, innovations et nouvelles orientations. PMID- 27199026 TI - Transformar nuestros entornos: haremos que suceda en todas partes. PMID- 27199029 TI - The influence of family pattern abnormalities in the early stages of life on the course of inflammatory bowel diseases. AB - Crohn's disease (CD) and ulcerative colitis (UC) belong to the group of inflammatory bowel diseases (IBD), chronic immune mediated diseases of the gastrointestinal (GI) tract with significant negative impact on patients' quality of life. CD and UC are related with the development of chronic inflammatory lesions in the GI tract, causing digestive and absorption disorders. Typical symptoms of IBD are: abdominal pain, vomiting, diarrhea, rectal bleeding, and weight loss. In addition, IBD are often associated with the extraintestinal manifestations, including arthritis and dermatoses. While the cause of IBD is still not fully understood, the psychological aspects are regarded as possible trigger factors. Moreover, most recent studies suggest that family pattern abnormalities associated with stress at the early stages of life may strongly affect health balance. In this paper, the most relevant studies focusing on the association between early life stress and IBD, found in MEDLINE, Cochrane Library and EMBASE are discussed. Possible effects of the early life stress on IBD progression and response to undertaken therapies are analyzed. PMID- 27199030 TI - Inducing Protein Degradation as a Therapeutic Strategy. PMID- 27199028 TI - LAMP Detection Assays for Boxwood Blight Pathogens: A Comparative Genomics Approach. AB - Rapid and accurate molecular diagnostic tools are critical to efforts to minimize the impact and spread of emergent pathogens. The identification of diagnostic markers for novel pathogens presents several challenges, especially in the absence of information about population diversity and where genetic resources are limited. The objective of this study was to use comparative genomics datasets to find unique target regions suitable for the diagnosis of two fungal species causing a newly emergent blight disease of boxwood. Candidate marker regions for loop-mediated isothermal amplification (LAMP) assays were identified from draft genomes of Calonectria henricotiae and C. pseudonaviculata, as well as three related species not associated with this disease. To increase the probability of identifying unique targets, we used three approaches to mine genome datasets, based on (i) unique regions, (ii) polymorphisms, and (iii) presence/absence of regions across datasets. From a pool of candidate markers, we demonstrate LAMP assay specificity by testing related fungal species, common boxwood pathogens, and environmental samples containing 445 diverse fungal taxa. This comparative genomics-based approach to the development of LAMP diagnostic assays is the first of its kind for fungi and could be easily applied to diagnostic marker development for other newly emergent plant pathogens. PMID- 27199031 TI - Accuracy of the pacemaker-mediated tachycardia algorithm in Boston Scientific devices. AB - INTRODUCTION: The incidence of pacemaker-mediated tachycardia (PMT) varies as a function of patient characteristics, device programming and algorithm specificities. We investigated the efficacy of the Boston Scientific algorithm by reviewing PMT episodes in a large device population. METHODS: In this multicenter study, we included 328 patients implanted with a Boston Scientific device: 157 non-dependent patients with RYTHMIQTM activated (RYTHMIQ group), 76 patients with permanent AV-conduction disorder (AV-block group) and 95 Cardiac Resynchronization Therapy patients (CRT group). For each patient, we reviewed the last 10 remote monitoring-transmitted EGMs diagnosed as PMT. RESULTS: We analyzed 784 PMT episodes across 118 patients. In the RYTHMIQ group, the diagnosis of PMT was correct in most episodes (80%) of which 69% was directly related to the prolongation of the AV-delay associated with the RYTHMIQ algorithm. The usual triggers for PMT were also observed (PVC 16%, PAC 9%). The remainder of the episodes (20%) in RYTHMIQ patients and most episodes of AV-block (66%) and CRT patients (74%) were incorrectly diagnosed as PMT during sinus tachycardia at the maximal tracking rate. The inappropriate intervention of the algorithm during exercise causes non-conducted P-waves, loss of CRT (sustained in six patients) and may have been pro-arrhythmogenic in one patient (induction of ventricular tachycardia). CONCLUSION: Algorithms to minimize ventricular pacing can occasionally have unintended consequences such as PMT. The PMT algorithm in Boston Scientific devices is associated with a high rate of incorrect PMT diagnosis during exercise resulting in inappropriate therapy with non-conducted P waves, loss of CRT and limited risk of pro-arrhythmic events. PMID- 27199032 TI - Interview with E. Harvey Estes. PMID- 27199033 TI - Effects of CYP2C19 variants on methadone metabolism in vitro. AB - CYP2C19 is an important member of the cytochrome P450 (CYP450) enzyme super family and is responsible for clearing approximately 10% of commonly used clinical drugs that undergo phase I metabolism. Genetic polymorphisms of CYP2C19 significantly influence the efficacy and safety of some drugs, which might cause undesirable adverse effects or cure failure at standard dosages. The aim of this study was to clarify the catalytic activities of 31 CYP2C19 alleles on the oxidative in vitro metabolism of methadone. Insect microsomes expressing the CYP2C19 alleles were incubated with 50-2000 MUM methadone for 30 min at 37 degrees C and terminated by cooling to -80 degrees C immediately. Methadone and its metabolite EDDP were analyzed by an ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) system. Of the 31 tested CYP2C19 allelies variants, CYP2C19*1 is the wild-type. Compared with CYP2C19*1, two CYP2C19 variants (CYP2C19*3 and *35FS) had no detectable enzyme activity, one variant L16F exhibited slightly increased intrinsic clearance values, and one variant N277K showed no significant difference. In addition, 26 variants exhibited significantly decreased values (from 1.48% to 80.40%). These findings suggest that more attention should be paid in clinical administration of methadone to individuals carrying these CYP2C19 alleles. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27199035 TI - Key role of scale morphology in flatfishes (Pleuronectiformes) in the ability to keep sand. AB - Flatfishes bury themselves for camouflage and protection. Whereas species specific preferences for certain sediments were previously shown, the role of scales in interaction with sediment has not been investigated. Here, scale morphology and sediment friction were examined in four European pleuronectiforms: Limanda limanda, Platichthys flesus, Pleuronectes platessa, and Solea solea. All species had different scale types ranging from cycloid to ctenoid scales. On the blind side, the number of scales is higher and scales have less ctenial spines than on the eye side. The critical angle of sediment sliding (static friction) significantly depended on the grain size and was considerably higher on the eye side. The effect of mucus was excluded by repeated measurements on resin replicas of the skin. Our results demonstrate the impact of scale morphology on sediment interaction and give an insight about the ability of scales to keep sand. Exposed scales and a higher number of ctenial spines on the eye side lead to an increase of friction forces, especially for sediments with a smaller grain size. Our results suggest that the evolution of scales was at least partly driven by their interactions with sediment which confirms the relevance of sediment for the distribution and radiation of Pleuronectiformes. PMID- 27199034 TI - The gut microbiota of the pine weevil is similar across Europe and resembles that of other conifer-feeding beetles. AB - The pine weevil (Hylobius abietis, Coleoptera: Curculionidae) is an important pest of conifer seedlings in Europe. Despite its economic importance, little is known about the composition of its gut microbial community and the role it plays in mediating the weevil's ability to utilize conifers as a food source. Here, we characterized the gut bacterial communities of different populations of H. abietis across Europe and compared them to those of other beetles that occupy similar ecological niches. We demonstrate that the microbial community of H. abietis is similar at higher taxonomic levels (family and genus) across locations in Europe, with Wolbachia as the dominant microbe, followed by Enterobacteria and Firmicutes. Despite this similarity, we observed consistent differences between countries and locations, but not sexes. Our meta-analysis demonstrates that the gut bacterial community of the pine weevil is very similar to that of bark beetles that also exploit conifers as a food source. The Enterobacteriaceae symbionts of both host taxa are especially closely related phylogenetically. Conversely, the microbiota of H. abietis is distinct from that of closely related weevils feeding on nonconifer food sources, suggesting that the microbial community of the pine weevil is determined by the environment and may be relevant to host ecology. Furthermore, several H. abietis-associated members of the Enterobacteriaceae family are known to contain genes involved in terpenoid degradation. As such, we hypothesize that the gut microbial community is important for the utilization of conifer seedlings as a food source, either through the detoxification of plant secondary metabolites or through the supplementation of essential nutrients. PMID- 27199037 TI - Tackling AMR: time to turn ideas into action. PMID- 27199038 TI - BVA renews calls for mandatory CCTV in slaughterhouses. PMID- 27199039 TI - Awards celebrate the best in veterinary marketing. PMID- 27199040 TI - Bluetongue: UK risk level remains the same as outbreaks continue in France. PMID- 27199042 TI - Encouraging debate on the EU referendum. PMID- 27199043 TI - Taking control of work-life balance. AB - For veterinary professionals, a key component of maintaining good wellbeing is being able to get to the end of a day feeling happy, content and in control. This, however, can prove challenging to achieve. Kristy Ebanks reports on a series of sessions from this year's BSAVA congress which focused on improving wellbeing. PMID- 27199044 TI - Incorporating reflection into veterinary practice. AB - New graduates are encouraged to reflect on their progress during their Professional Development Phase, but what does reflection really mean, and how can veterinary professionals use it to better their day-to-day practice? This was a topic discussed during an afternoon of sessions at the recent BSAVA congress in Birmingham. Georgina Mills reports. PMID- 27199045 TI - Dogs Trust rewards the best EMS reports. PMID- 27199046 TI - Northern Ireland disease surveillance report, January to March 2016. AB - Abomasitis in calvesAortic aneurysm in a dairy cowAbortion due to Salmonella Brandenberg in ewesStreptococcus dysgalactia polyarthritis in lambs These are among matters discussed in the Northern Ireland animal disease surveillance quarterly report for January to March 2016. PMID- 27199047 TI - Technical innovation in equine radiology: what's changed? PMID- 27199048 TI - Dog bites - are vets missing an educational opportunity? AB - Veterinary surgeons have a key role to play in tackling the public health problem of dog bites, say CHRISTOPHER MANNION: and DANIELLE GREENBERG: , who argue that a multiprofessional approach to the problem is needed. PMID- 27199049 TI - Hospice and palliative care. PMID- 27199050 TI - Hospice and palliative care. PMID- 27199051 TI - Welfare of exotic pets. PMID- 27199052 TI - Brachycephalic dog breeds. PMID- 27199053 TI - Research opens more doors. AB - Having gained some clinical experience before pursuing a research career, Lucy Davison is now seeking the best of both worlds as a clinician scientist. PMID- 27199054 TI - Outcomes in Moderate Mixed Aortic Valve Disease: Is it Time for a Paradigm Shift? AB - BACKGROUND: A direct comparison of outcomes between moderate mixed aortic valve disease (MAVD) and isolated aortic stenosis (AS) or aortic regurgitation (AR) has not been performed, making evidence-based recommendations difficult in patients with MAVD. OBJECTIVES: This study sought to determine adverse event (AE) occurrence (the primary endpoint), defined as New York Heart Association functional class III/IV symptoms, aortic valve replacement, or cardiac death, and to compare AE rates between MAVD and isolated AS or AR. METHODS: Asymptomatic patients were identified with moderate MAVD and an ejection fraction >=50% and were followed at Mayo Clinic from 1994 to 2013. Moderate MAVD was defined as a combination of moderate AS and moderate AR. Age- and sex-matched control groups were selected with isolated moderate AR (n = 117), moderate AS (n = 117), or severe AS (n = 117). RESULTS: At 9.1 +/- 4.2 years of follow-up, patients with moderate MAVD (n = 251) had a mean age of 63 +/- 11 years, 73% were male, and 38% had bicuspid valve. AE occurred in 193 (77%) patients in this group, including symptom development (69%), aortic valve replacement (67%), and cardiac death (4%). Predictors of AE were older age (hazard ratio [HR]: 1.71 per decade; 95% confidence interval [CI]: 1.38 to 1.97 per decade; p = 0.001), and relative wall thickness >0.42 (HR: 2.01; 95% CI: 1.86 to 2.33; p = 0.002). AE rates were similar in the MAVD and severe AS group (71% vs. 68% at 5 years; p = 0.49), but were significantly higher compared with the moderate AS and AR groups. CONCLUSIONS: MAVD patients had outcomes comparable to those with severe AS, and preserved ejection fraction and should be monitored closely for symptoms. PMID- 27199055 TI - The Simple Arithmetic of Mixed Aortic Valve Disease: LVH + Volume Load = Trouble. PMID- 27199056 TI - Papillary Muscle Approximation Versus Restrictive Annuloplasty Alone for Severe Ischemic Mitral Regurgitation. AB - BACKGROUND: Guidelines recommend surgery for patients with severe ischemic mitral regurgitation (MR). Nonrandomized studies suggest that subvalvular repair is associated with longer survival, but randomized studies are lacking. OBJECTIVES: This study sought to investigate the benefit of papillary muscle surgery on long term clinical outcomes of patients with ischemic MR. METHODS: Ninety-six patients with severe ischemic MR were randomized to either undersizing restrictive mitral annuloplasty (RA) or papillary muscle approximation with undersizing restrictive mitral annuloplasty (PMA) associated with complete surgical myocardial revascularization. The primary endpoint was change in left ventricular end diastolic diameter (LVEDD) after 5 years, measured as the absolute difference from baseline, which was evaluated by paired Student t tests. Secondary endpoints included changes in echocardiographic parameters, overall mortality, the composite cardiac endpoint (major adverse cardiac and cerebrovascular events [MACCE]), and quality of life (QOL) during the 5-year follow-up. RESULTS: At 5 years, mean LVEDD was 56.5 +/- 5.7 mm with PMA versus 60.6 +/- 4.6 mm with RA (mean change from baseline -5.8 +/- 4.1 mm and -0.2 +/- 2.3 mm, respectively; p < 0.001). Ejection fraction was 44.1 +/- 6% in the PMA group versus 39.9 +/- 3.9% in the RA group (mean change from baseline 8.8 +/- 5.9% and 2.5 +/- 4.3%, respectively; p < 0.001). There was no statistically significant difference in mortality at 5 years, but freedom from MACCE favored PMA in the last year of follow-up. PMA significantly reduced tenting height, tenting area, and interpapillary distance soon after surgery and for the long-term, and significantly lowered moderate-to-severe MR recurrence. No differences were found in QOL measures. CONCLUSIONS: Compared with RA only, PMA exerted a long-term beneficial effect on left ventricular remodeling and more effectively restored the mitral valve geometric configuration in ischemic MR, which improved long-term cardiac outcomes, but did not produce differences in overall mortality and QOL. PMID- 27199057 TI - How Do We Ensure a "Good" Repair in Ischemic Mitral Regurgitation? PMID- 27199059 TI - The Complex Interaction Between Left Ventricular Ejection Fraction, Flow, and Gradient in Patients Undergoing TAVR. PMID- 27199058 TI - Impact of Ejection Fraction and Aortic Valve Gradient on Outcomes of Transcatheter Aortic Valve Replacement. AB - BACKGROUND: In patients with aortic stenosis undergoing transcatheter aortic valve replacement (TAVR), studies have suggested that reduced left ventricular (LV) ejection fraction (LVEF) and low aortic valve gradient (AVG) are associated with worse long-term outcomes. Because these conditions commonly coexist, the extent to which they are independently associated with outcomes after TAVR is unknown. OBJECTIVES: The purpose of this study was to evaluate the impact of LVEF and AVG on clinical outcomes after TAVR and to determine whether the effect of AVG on outcomes is modified by LVEF. METHODS: Using data from 11,292 patients who underwent TAVR as part of the Transcatheter Valve Therapies Registry, we examined rates of 1-year mortality and recurrent heart failure in patients with varying levels of LV dysfunction (LVEF <30% vs. 30% to 50% vs. >50%) and AVG (<40 mm Hg vs. >=40 mm Hg). Multivariable models were used to estimate the independent effect of AVG and LVEF on outcomes. RESULTS: During the first year of follow-up after TAVR, patients with LV dysfunction and low AVG had higher rates of death and recurrent heart failure. After adjustment for other clinical factors, only low AVG was associated with higher mortality (hazard ratio: 1.21; 95% confidence interval: 1.11 to 1.32; p < 0.001) and higher rates of heart failure (hazard ratio: 1.52; 95% confidence interval: 1.36 to 1.69; p <0.001), whereas the effect of LVEF was no longer significant. There was no evidence of effect modification between AVG and LVEF with respect to either endpoint. CONCLUSIONS: In this series of real-world patients undergoing TAVR, low AVG, but not LV dysfunction, was associated with higher rates of mortality and recurrent heart failure. Although these findings suggest that AVG should be considered when evaluating the risks and benefits of TAVR for individual patients, neither severe LV dysfunction nor low AVG alone or in combination provide sufficient prognostic discrimination to preclude treatment with TAVR. PMID- 27199060 TI - Pheochromocytoma Is Characterized by Catecholamine-Mediated Myocarditis, Focal and Diffuse Myocardial Fibrosis, and Myocardial Dysfunction. AB - BACKGROUND: Pheochromocytoma is associated with catecholamine-induced cardiac toxicity, but the extent and nature of cardiac involvement in clinical cohorts is not well-characterized. OBJECTIVES: This study characterized the cardiac phenotype in patients with pheochromocytoma using cardiac magnetic resonance (CMR). METHODS: A total of 125 subjects were studied, including patients with newly diagnosed pheochromocytoma (n = 29), patients with previously surgically cured pheochromocytoma (n = 31), healthy control subjects (n = 51), and hypertensive control subjects (HTN) (n = 14), using CMR (1.5-T) cine, strain imaging by myocardial tagging, late gadolinium enhancement, and native T1 mapping (Shortened Modified Look-Locker Inversion recovery [ShMOLLI]). RESULTS: Patients who were newly diagnosed with pheochromocytoma, compared with healthy and HTN control subjects, had impaired left ventricular (LV) ejection fraction (<56% in 38% of patients), peak systolic circumferential strain (p < 0.05), and diastolic strain rate (p < 0.05). They had higher myocardial T1 (974 +/- 25 ms, as compared with 954 +/- 16 ms in healthy and 958 +/- 23 ms in HTN subjects; p < 0.05), areas of myocarditis (median 22% LV with T1 >990 ms, as compared with 1% in healthy and 2% in HTN subjects; p < 0.05), and focal fibrosis (59% had nonischemic late gadolinium enhancement, as compared with 14% in HTN subjects). Post-operatively, impaired LV ejection fraction typically normalized, but systolic and diastolic strain impairment persisted. Focal fibrosis (median 5% LV) and T1 abnormalities (median 12% LV) remained, the latter of which may suggest some diffuse fibrosis. Previously cured patients demonstrated abnormal diastolic strain rate (p < 0.001), myocardial T1 (median 12% LV), and small areas of focal fibrosis (median 1% LV). LV mass index was increased in HTN compared with healthy control subjects (p < 0.05), but not in the 2 pheochromocytoma groups. CONCLUSIONS: This first systematic CMR study characterizing the cardiac phenotype in pheochromocytoma showed that cardiac involvement was frequent and, for some variables, persisted after curative surgery. These effects surpass those of hypertensive heart disease alone, supporting a direct role of catecholamine toxicity that may produce subtle but long-lasting myocardial alterations. PMID- 27199061 TI - Stressing the Importance of Cardiac Assessment in Pheochromocytoma. PMID- 27199063 TI - Closing the Gap Between Clinical Trials and Practice: A Global Imperative. PMID- 27199062 TI - Association of Guideline-Based Admission Treatments and Life Expectancy After Myocardial Infarction in Elderly Medicare Beneficiaries. AB - BACKGROUND: Guideline-based admission therapies for acute myocardial infarction (AMI) significantly improve 30-day survival, but little is known about their association with long-term outcomes. OBJECTIVES: This study evaluated the association of 5 AMI admission therapies (aspirin, beta-blockers, acute reperfusion therapy, door-to-balloon [D2B] time <=90 min, and time to fibrinolysis <=30 min) with life expectancy and years of life saved after AMI. METHODS: We analyzed data from the Cooperative Cardiovascular Project, a study of Medicare beneficiaries hospitalized for AMI, with 17 years of follow-up. Life expectancy and years of life saved after AMI were calculated using Cox proportional hazards regression with extrapolation using exponential models. RESULTS: Survival for recipients and non-recipients of the 5 guideline-based therapies diverged early after admission and continued to diverge during 17-year follow-up. Receipt of aspirin, beta-blockers, and acute reperfusion therapy on admission was associated with longer life expectancy of 0.78 (standard error [SE]: 0.05), 0.55 (SE: 0.06), and 1.03 (SE: 0.12) years, respectively. Patients receiving primary percutaneous coronary intervention (PCI) within 90 min lived 1.08 (SE: 0.49) years longer than patients with D2B times >90 min, and door-to needle (D2N) times <=30 min were associated with 0.55 (SE: 0.12) more years of life. A dose-response relationship was observed between longer D2B and D2N times and shorter life expectancy after AMI. CONCLUSIONS: Guideline-based therapy for AMI admission is associated with both early and late survival benefits, and results in meaningful gains in life expectancy and large numbers of years of life saved in elderly patients. PMID- 27199064 TI - Statin-Associated Side Effects. AB - Hydroxy-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors or statins are well tolerated, but associated with various statin-associated symptoms (SAS), including statin-associated muscle symptoms (SAMS), diabetes mellitus (DM), and central nervous system complaints. These are "statin-associated symptoms" because they are rare in clinical trials, making their causative relationship to statins unclear. SAS are, nevertheless, important because they prompt dose reduction or discontinuation of these life-saving mediations. SAMS is the most frequent SAS, and mild myalgia may affect 5% to 10% of statin users. Clinically important muscle symptoms, including rhabdomyolysis and statin-induced necrotizing autoimmune myopathy (SINAM), are rare. Antibodies against HMG-CoA reductase apparently provoke SINAM. Good evidence links statins to DM, but evidence linking statins to other SAS is largely anecdotal. Management of SAS requires making the possible diagnosis, altering or discontinuing the statin treatment, and using alternative lipid-lowering therapy. PMID- 27199067 TI - Pharmacokinetics and Pharmacodynamics of Dabigatran 75 mg b.i.d. in Patients With Severe Chronic Kidney Disease. PMID- 27199065 TI - Heavy Metals, Cardiovascular Disease, and the Unexpected Benefits of Chelation Therapy. AB - This review summarizes evidence from 2 lines of research previously thought to be unrelated: the unexpectedly positive results of TACT (Trial to Assess Chelation Therapy), and a body of epidemiological data showing that accumulation of biologically active metals, such as lead and cadmium, is an important risk factor for cardiovascular disease. Considering these 2 areas of work together may lead to the identification of new, modifiable risk factors for atherosclerotic cardiovascular disease. We examine the history of chelation up through the report of TACT. We then describe work connecting higher metal levels in the body with the future risk of cardiovascular disease. We conclude by presenting a brief overview of a newly planned National Institutes of Health trial, TACT2, in which we will attempt to replicate the findings of TACT and to establish that removal of toxic metal stores from the body is a plausible mechanistic explanation for the benefits of edetate disodium treatment. PMID- 27199068 TI - Underutilization of Anticoagulation for Stroke Prevention in Atrial Fibrillation. PMID- 27199066 TI - Assessment of Administrative Data to Identify Acute Myocardial Infarction in Electronic Health Records. PMID- 27199069 TI - Inconsistency of Hemodynamic Data in Low-Gradient Severe Aortic Stenosis. PMID- 27199070 TI - Paradoxical Low-Gradient Aortic Stenosis: The HFpEF of Aortic Stenosis. PMID- 27199071 TI - Reply: Inconsistency of Hemodynamic Data in Low-Gradient Severe Aortic Stenosis: Paradoxical Low-Gradient Aortic Stenosis: The HFpEF of Aortic Stenosis. PMID- 27199072 TI - Mechanical Thrombectomy for Ischemic Stroke. PMID- 27199073 TI - Reply: Mechanical Thrombectomy for Ischemic Stroke. PMID- 27199074 TI - Pharmacological rescue of hERG currents carried out by G604S and wide type hERG co-expression. AB - Mutations in human ether-a-go-go-related gene (hERG) can lead to type 2 long-QT syndrome (LQT2). The authors previously identified the hERG mutation G604S results in a loss of function and obviously decreased current amplitude and impaired channel protein trafficking when co-expressed with WT-hERG. The present study further investigates the biological and electrophysiological consequences of pharmacologic chaperones in HEK293 cells expressing G604S-hERG or co expressing G604S-hERG and WT-hERG. It was found that a low temperature (27 degrees C), thapsigargin, NS1643 and E-4031 fail to rescue the G604S mutation. Interestingly, only E-4031 treatment resulted in a significant increase in hERG currents in cells co-expressing G604S-hERG and WT-hERG, correspondingly more mature protein band at 155 kDa by Western blotting and an increased membrane staining by confocal microscopy. In addition, E-4031 treatment shifted the steady state half maximal activation voltage (V1/2 ) of the inactivation curve by +8 mV in cells co-expressing G604S-hERG and WT-hERG. The present experimental results suggest that a G604S mutation is resistant to pharmacological rescue. E-4031 treatment resulted in a significant increase in hERG currents by promoting the hERG channel processing and trafficking in cells co-expressing G604S-hERG and WT hERG. PMID- 27199076 TI - Introduction. PMID- 27199077 TI - Cytological diagnosis of metastatic malignant melanoma by fine-needle aspiration biopsy. AB - Despite increased surveillance and public awareness, the incidence of melanoma is increasing. Frequently, fine-needle aspiration is employed for the diagnosis of metastatic disease, and aspirated material is used for cytogenetic and molecular studies to guide treatment options. The pairing of a significant diagnosis with the numerous morphologic variants of melanoma can make the cytologic evaluation disquieting. We present selected examples of our experiences and a brief review of the literature to provide cytodiagnostic clues for this malignancy. The clinical history is foremost, although the fine-needle aspiration (FNA) of metastatic melanoma can provide a diagnosis before identification of the primary lesion in up to 20% of cases. If a history of melanoma is assured, negative results in sampling of pulmonary and subcutaneous nodules should be suspected as false negatives. The smearing pattern usually features poorly cohesive cells. Frankly malignant, spindled, and epithelioid cell shapes are most common, and cytoplasmic vacuoles, if sought on Romanowsky-stained specimens, can usually be found. The telltale feature of melanin production, although diagnostic, is only present in 50% of cases. Finally, eccentric placement of nuclei, nucleoli, and nuclear pseudoinclusions are accessory features for the cytologic interpretation of melanoma. Numerous morphologic patterns of melanoma are potentially seen, but a stepwise approach to diagnosis usually produces a successful result. PMID- 27199075 TI - TNF and IL-1beta exposure increases airway narrowing but does not alter the bronchodilatory response to deep inspiration in airway segments. AB - BACKGROUND AND OBJECTIVE: While chronic inflammation of the airway wall and the failure of deep inspiration (DI) to produce bronchodilation are both common to asthma, whether pro-inflammatory cytokines modulate the airway smooth muscle response to strain during DI is unknown. The primary aim of the study was to determine how an inflammatory environment (simulated by the use of pro inflammatory cytokines) alters the bronchodilatory response to DI. METHODS: We used whole porcine bronchial segments in vitro that were cultured in medium containing tumour necrosis factor and interleukin-1beta for 2 days. A custom built servo-controlled syringe pump and pressure transducer was used to measure airway narrowing and to simulate tidal breathing with intermittent DI manoeuvres. RESULTS: Culture with tumour necrosis factor and interleukin-1beta increased airway narrowing to acetylcholine but did not affect the bronchodilatory response to DI. CONCLUSION: The failure of DI to produce bronchodilation in patients with asthma may not necessarily involve a direct effect of pro-inflammatory cytokines on airway tissue. A relationship between inflammation and airway hyper responsiveness is supported, however, regulated by separate disease processes than those which attenuate or abolish the bronchodilatory response to DI in patients with asthma. PMID- 27199078 TI - Blue nevus and "malignant blue nevus:" A concise review. AB - Blue nevi are a heterogeneous group of lesions that can display a variety of different clinicopathological characteristics. Although attempts are made to classify each lesion into defined subtypes, there can be overlap between the subtypes. The clinical and histolopathologic features of common blue nevi and cellular blue nevi are discussed, as well as blue nevi with atypical features and malignant lesions with features of blue nevi. PMID- 27199079 TI - van der Waals epitaxy and photoresponse of two-dimensional CdSe plates. AB - Here we demonstrate the first growth of two-dimensional (2D) single-crystalline CdSe plates on mica substrates via van der Waals epitaxy. The as-synthesized 2D plates exhibit hexagonal, truncated triangular and triangular shapes with the lateral size around several microns. Photodetectors based on 2D CdSe plates present a fast response time of 24 ms, revealing that 2D CdSe is a promising building block for ultrathin optoelectronic devices. PMID- 27199080 TI - A bulk sub-femtoliter in vitro compartmentalization system using super-fine electrosprays. AB - The extreme miniaturization of biological and chemical assays in aqueous-droplet compartments enables spatiotemporal control for large-scale parallel experimentation and can thus permit new capabilities for "digitizing" directed molecular evolution methodologies. We report a remarkably facile bulk method to generate mega-scale monodisperse sub-femtoliter aqueous droplets by electrospray, using a prototype head with super-fine inkjet technology. Moreover, the electrostatic inkjet nozzle that injects the aqueous phase when immersed within an immiscible phase (an optimized oil/surfactant mixture) has the advantage of generating cell-like sub-femtoliter compartments for biomolecule encapsulation and successive biological and chemical reactions. Sub-femtoliter droplets of both liquid (water-in-oil, volumes ranging from 0.2 to 6.4 fL) and gel bead (agarose in-oil, volume ranging from 0.3 to 15.6 fL) compartments with average sizes of 1.3 MUm and 1.5 MUm, respectively, were successfully generated using an inkjet nozzle at a speed of more than 10(5) droplets per second. We demonstrated the applicability of this system by synthesizing fluorescent proteins using a cell free expression system inside electrosprayed sub-femtoliter droplets at an accelerated rate, thereby extending the utility of in vitro compartmentalization with improved analytical performance for a top-down artificial cellular system. PMID- 27199081 TI - Knr4: a disordered hub protein at the heart of fungal cell wall signalling. AB - The most highly connected proteins in protein-protein interactions networks are called hubs; they generally connect signalling pathways. In Saccharomyces cerevisiae, Knr4 constitutes a connecting node between the two main signal transmission pathways involved in cell wall maintenance upon stress: the cell wall integrity and the calcium-calcineurin pathway. Knr4 is required to enable the cells to resist many cell wall-affecting stresses, and KNR4 gene deletion is synthetic lethal with the simultaneous deletion of numerous other genes involved in morphogenesis and cell wall biogenesis. Knr4 has been shown to engage in multiple physical interactions, an ability conferred by the intrinsic structural adaptability of major disordered regions present in the N-terminal and C-terminal parts of the protein. Taking all together, Knr4 is an intrinsically disordered hub protein. Available data from other fungi indicate the conservation of Knr4 homologs cellular function and localization at sites of polarized growth among fungal species, including pathogenic species. Because of their particular role in morphogenesis control and of their fungal specificity, these proteins could constitute interesting new pharmaceutical drug targets for antifungal combination therapy. PMID- 27199083 TI - Pressure dependent low temperature kinetics for CN + CH3CN: competition between chemical reaction and van der Waals complex formation. AB - The gas phase reaction between the CN radical and acetonitrile CH3CN was investigated experimentally, at low temperatures, with the CRESU apparatus and a slow flow reactor to explore the temperature dependence of its rate coefficient from 354 K down to 23 K. Whereas a standard Arrhenius behavior was found at T > 200 K, indicating the presence of an activation barrier, a dramatic increase in the rate coefficient by a factor of 130 was observed when the temperature was decreased from 168 to 123 K. The reaction was found to be pressure independent at 297 K unlike the experiments carried out at 52 and 132 K. The work was complemented by ab initio transition state theory based master equation calculations using reaction pathways investigated with highly accurate thermochemical protocols. The role of collisional stabilization of a CNCH3CN van der Waals complex and of tunneling induced H atom abstractions were also considered. The experimental pressure dependence at 52 and 132 K is well reproduced by the theoretical calculations provided that an anharmonic state density is considered for the van der Waals complex CH3CNCN and its Lennard-Jones radius is adjusted. Furthermore, these calculations indicate that the experimental observations correspond to the fall-off regime and that tunneling remains small in the low-pressure regime. Hence, the studied reaction is essentially an association process at very low temperature. Implications for the chemistry of interstellar clouds and Titan are discussed. PMID- 27199082 TI - Magnetic susceptibility anisotropy outside the central nervous system. AB - Magnetic-susceptibility-based MRI has made important contributions to the characterization of tissue microstructure, chemical composition, and organ function. This has motivated a number of studies to explore the link between microstructure and susceptibility in organs and tissues throughout the body, including the kidney, heart, and connective tissue. These organs and tissues have anisotropic magnetic susceptibility properties and cellular organizations that are distinct from the lipid organization of myelin in the brain. For instance, anisotropy is traced to the epithelial lipid orientation in the kidney, the myofilament proteins in the heart, and the collagen fibrils in the knee cartilage. The magnetic susceptibility properties of these and other tissues are quantified using specific MRI tools: susceptibility tensor imaging (STI), quantitative susceptibility mapping (QSM), and individual QSM measurements with respect to tubular and filament directions determined from diffusion tensor imaging. These techniques provide complementary and supplementary information to that produced by traditional MRI methods. In the kidney, STI can track tubules in all layers including the cortex, outer medulla, and inner medulla. In the heart, STI detected myofibers throughout the myocardium. QSM in the knee revealed three unique layers in articular cartilage by exploiting the anisotropic susceptibility features of collagen. While QSM and STI are promising tools to study tissue susceptibility, certain technical challenges must be overcome in order to realize routine clinical use. This paper reviews essential experimental findings of susceptibility anisotropy in the body, the underlying mechanisms, and the associated MRI methodologies. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27199084 TI - Dual trigger with gonadotropin-releasing hormone agonist and recombinant human chorionic gonadotropin improves in vitro fertilization outcome in gonadotropin releasing hormone antagonist cycles. AB - AIM: The aim of this study was to evaluate whether dual trigger with leuprolide acetate plus recombinant human chorionic gonadotropin (hCG) improves in vitro fertilization outcome in gonadotropin-releasing hormone antagonist cycles. METHODS: A total of 156 patients diagnosed with mild male factor, unexplained or tubal factor infertility were enrolled in the study. All subjects were allocated into one of two groups: the dual trigger group (leuprolide acetate 500 MUg + recombinant hCG 250 MUg) and the standard group (recombinant hCG 250 MUg) according to the selected trigger method. Oocyte trigger was performed when at least three follicles >17 mm were observed. Pregnancy rate, number of collected oocytes, number of metaphase II oocytes, number of grade-A embryos, cycle cancellation rate, and ovarian hyperstimulation syndrome rate were the main outcome measures for the study. RESULTS: The mean number of grade-A embryos (1.6 +/- 1.5 vs 1.1 +/- 1.4, P = 0.01) and of metaphase II oocytes (7.9 +/- 4.6 vs 6.3 +/- 5.8, P = 0.02) was significantly higher in the dual-trigger group. Pregnancy rate was significantly higher in the dual-trigger group than in the standard group (54.8 vs 37.5%, P = 0.006). Two cases of mild ovarian hyperstimulation syndrome were observed in each group. CONCLUSION: This novel and more physiological trigger approach using 500 MUg leuprolide acetate plus 250 MUg recombinant hCG may lead to an increase in the number of metaphase II oocytes, grade-A embryos, and may improve pregnancy rates. PMID- 27199085 TI - Alternative perspectives of safety in home delivered health care: a sequential exploratory mixed method study. AB - AIM: The aim of this study was to discover and describe how patients, carers and case management nurses define safety and compare it to the traditional risk reduction and harm avoidance definition of safety. BACKGROUND: Care services are increasingly being delivered in the home for patients with complex long-term conditions. However, the concept of safety remains largely unexplored. DEIGN: A sequential, exploratory mixed method design. METHODS: A qualitative case study of the UK National Health Service case management programme in the English UK National Health Service was deployed during 2012. Thirteen interviews were conducted with patients (n = 9) and carers (n = 6) and three focus groups with nurses (n = 17) from three community care providers. The qualitative element explored the definition of safety. Data were subjected to framework analysis and themes were identified by participant group. Sequentially, a cross-sectional survey was conducted during 2013 in a fourth community care provider (patient n = 35, carer n = 19, nurse n = 26) as a form of triangulation. FINDINGS: Patients and carers describe safety differently to case management nurses, choosing to focus on meeting needs. They use more positive language and recognize the role they have in safety in home-delivered health care. In comparison, case management nurses described safety similarly to the definitions found in the literature. However, when offered the patient and carer definition of safety, they preferentially selected this definition to their own or the literature definition. CONCLUSION: Patients and carers offer an alternative perspective on patient safety in home-delivered health care that identifies their role in ensuring safety and is more closely aligned with the empowerment philosophy of case management. PMID- 27199086 TI - Is STAN monitoring associated with a significant decrease in metabolic acidosis at birth compared with cardiotocography alone? Review of the three meta-analyses that included the recent US trial. PMID- 27199088 TI - Systemic Gene Transfer of a Hexosaminidase Variant Using an scAAV9.47 Vector Corrects GM2 Gangliosidosis in Sandhoff Mice. AB - GM2 gangliosidosis is a group of neurodegenerative diseases caused by beta hexosaminidase A (HexA) enzyme deficiency. There is currently no cure. HexA is composed of two similar, nonidentical subunits, alpha and beta, which must interact with the GM2 activator protein (GM2AP), a substrate-specific cofactor, to hydrolyze GM2 ganglioside. Mutations in either subunit or the activator can result in the accumulation of GM2 ganglioside within neurons throughout the central nervous system. The resulting neuronal cell death induces the primary symptoms of the disease: motor impairment, seizures, and sensory impairments. This study assesses the long-term effects of gene transfer in a Sandhoff (beta subunit knockout) mouse model. The study utilized a modified human beta hexosaminidase alpha-subunit (MU-subunit) that contains critical sequences from the beta-subunit that enables formation of a stable homodimer (HexM) and interaction with GM2AP to hydrolyze GM2 ganglioside. We investigated a self complementary adeno-associated viral (scAAV) vector expressing HexM, through intravenous injections of the neonatal mice. We monitored one cohort for 8 weeks and another cohort long-term for survival benefit, behavioral, biochemical, and molecular analyses. Untreated Sandhoff disease (SD) control mice reached a humane endpoint at approximately 15 weeks, whereas treated mice had a median survival age of 40 weeks, an approximate 2.5-fold survival advantage. On behavioral tests, the treated mice outperformed their knockout age-matched controls and perform similarly to the heterozygous controls. Through the enzymatic and GM2 ganglioside analyses, we observed a significant decrease in the GM2 ganglioside level, even though the enzyme levels were not significantly increased. Molecular analyses revealed a global distribution of the vector between brain and spinal cord regions. In conclusion, the neonatal delivery of a novel viral vector expressing the human HexM enzyme is effective in ameliorating the SD mouse phenotype for long-term. Our data could have implications not only for treatment of SD but also for Tay-Sachs disease (alpha-subunit deficiency) and similar brain disorders. PMID- 27199089 TI - A two-step approach to achieve secondary amide transamidation enabled by nickel catalysis. AB - A long-standing challenge in synthetic chemistry is the development of the transamidation reaction. This process, which involves the conversion of one amide to another, is typically plagued by unfavourable kinetic and thermodynamic factors. Although some advances have been made with regard to the transamidation of primary amide substrates, secondary amide transamidation has remained elusive. Here we present a simple two-step approach that allows for the elusive overall transformation to take place using non-precious metal catalysis. The methodology proceeds under exceptionally mild reaction conditions and is tolerant of amino acid-derived nucleophiles. In addition to overcoming the classic problem of secondary amide transamidation, our studies expand the growing repertoire of new transformations mediated by base metal catalysis. PMID- 27199090 TI - A Comparison of the neural correlates that underlie rule-based and information integration category learning. AB - The influential competition between verbal and implicit systems (COVIS) model proposes that category learning is driven by two competing neural systems-an explicit, verbal, system, and a procedural-based, implicit, system. In the current fMRI study, participants learned either a conjunctive, rule-based (RB), category structure that is believed to engage the explicit system, or an information-integration category structure that is thought to preferentially recruit the implicit system. The RB and information-integration category structures were matched for participant error rate, the number of relevant stimulus dimensions, and category separation. Under these conditions, considerable overlap in brain activation, including the prefrontal cortex, basal ganglia, and the hippocampus, was found between the RB and information integration category structures. Contrary to the predictions of COVIS, the medial temporal lobes and in particular the hippocampus, key regions for explicit memory, were found to be more active in the information-integration condition than in the RB condition. No regions were more activated in RB than information integration category learning. The implications of these results for theories of category learning are discussed. Hum Brain Mapp 37:3557-3574, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27199087 TI - Pediatric Sarcomas Are Targetable by MR-Guided High Intensity Focused Ultrasound (MR-HIFU): Anatomical Distribution and Radiological Characteristics. AB - BACKGROUND: Despite intensive therapy, children with metastatic and recurrent sarcoma or neuroblastoma have a poor prognosis. Magnetic resonance guided high intensity focused ultrasound (MR-HIFU) is a noninvasive technique allowing the delivery of targeted ultrasound energy under MR imaging guidance. MR-HIFU may be used to ablate tumors without ionizing radiation or target chemotherapy using hyperthermia. Here, we evaluated the anatomic locations of tumors to assess the technical feasibility of MR-HIFU therapy for children with solid tumors. PROCEDURE: Patients with sarcoma or neuroblastoma with available cross-sectional imaging were studied. Tumors were classified based on the location and surrounding structures within the ultrasound beam path as (i) not targetable, (ii) completely or partially targetable with the currently available MR-HIFU system, and (iii) potentially targetable if a respiratory motion compensation technique was used. RESULTS: Of the 121 patients with sarcoma and 61 patients with neuroblastoma, 64% and 25% of primary tumors were targetable at diagnosis, respectively. Less than 20% of metastases at diagnosis or relapse were targetable for both sarcoma and neuroblastoma. Most targetable lesions were located in extremities or in the pelvis. Respiratory motion compensation may increase the percentage of targetable tumors by 4% for sarcomas and 10% for neuroblastoma. CONCLUSIONS: Many pediatric sarcomas are localized at diagnosis and are targetable by current MR-HIFU technology. Some children with neuroblastoma have bony tumors targetable by MR-HIFU at relapse, but few newly diagnosed children with neuroblastoma have tumors amenable to MR-HIFU therapy. Clinical trials of MR HIFU should focus on patients with anatomically targetable tumors. PMID- 27199091 TI - MY APPROACH to the use of chelation therapy. PMID- 27199092 TI - Temperature variability is a key component in accurately forecasting the effects of climate change on pest phenology. AB - BACKGROUND: Models describing the effects of climate change on arthropod pest ecology are needed to help mitigate and adapt to forthcoming changes. Challenges arise because climate data are at resolutions that do not readily synchronize with arthropod biology. Here we explain how multiple sources of climate and weather data can be synthesized to quantify the effects of climate change on pest phenology. RESULTS: Predictions of phenological events differ substantially between models that incorporate scale-appropriate temperature variability and models that do not. As an illustrative example, we predicted adult emergence of a pest of sunflower, the sunflower stem weevil Cylindrocopturus adspersus (LeConte). Predictions of the timing of phenological events differed by an average of 11 days between models with different temperature variability inputs. Moreover, as temperature variability increases, developmental rates accelerate. CONCLUSION: Our work details a phenological modeling approach intended to help develop tools to plan for and mitigate the effects of climate change. Results show that selection of scale-appropriate temperature data is of more importance than selecting a climate change emission scenario. Predictions derived without appropriate temperature variability inputs will likely result in substantial phenological event miscalculations. Additionally, results suggest that increased temperature instability will lead to accelerated pest development. (c) 2016 Society of Chemical Industry. PMID- 27199093 TI - Editorial overview: Remapping the body of the world: Exploring interactions at the interface of microbial ecology, biological engineering and information science. PMID- 27199094 TI - Kinetics of formation of bile salt micelles from coarse-grained Langevin dynamics simulations. AB - We examine the mechanism of formation of micelles of dihydroxy bile salts using a coarse-grained, implicit solvent model and Langevin dynamics simulations. We find that bile salt micelles primarily form via addition and removal of monomers, similarly to surfactants with typical head-tail molecular structures, and not via a two-stage mechanism - involving formation of oligomers and their subsequent aggregation to form larger micelles - originally proposed for bile salts. The free energy barrier to removal of single bile monomers from micelles is ~2kBT, much less than what has been observed for head-tail surfactants. Such a low barrier may be biologically relevant: it allows for rapid release of bile monomers into the intestine, possibly enabling the coverage of fat droplets by bile salt monomers and subsequent release of micelles containing fats and bile salts - a mechanism that is not possible for ionic head-tail surfactants of similar critical micellar concentrations. PMID- 27199095 TI - Immediate Closures and Violations Identified During Routine Inspections of Public Aquatic Facilities - Network for Aquatic Facility Inspection Surveillance, Five States, 2013. AB - PROBLEM/CONDITION: Aquatic facility-associated illness and injury in the United States include disease outbreaks of infectious or chemical etiology, drowning, and pool chemical-associated health events (e.g., respiratory distress or burns). These conditions affect persons of all ages, particularly young children, and can lead to disability or even death. A total of 650 aquatic facility-associated outbreaks have been reported to CDC for 1978-2012. During 1999-2010, drownings resulted in approximately 4,000 deaths each year in the United States. Drowning is the leading cause of injury deaths in children aged 1-4 years, and approximately half of fatal drownings in this age group occur in swimming pools. During 2003-2012, pool chemical-associated health events resulted in an estimated 3,000-5,000 visits to U.S. emergency departments each year, and approximately half of the patients were aged <18 years. In August 2014, CDC released the Model Aquatic Health Code (MAHC), national guidance that can be adopted voluntarily by state and local jurisdictions to minimize the risk for illness and injury at public aquatic facilities. REPORTING PERIOD COVERED: 2013. DESCRIPTION OF SYSTEM: The Network for Aquatic Facility Inspection Surveillance (NAFIS) was established by CDC in 2013. NAFIS receives aquatic facility inspection data collected by environmental health practitioners when assessing the operation and maintenance of public aquatic facilities. This report presents inspection data that were reported by 16 public health agencies in five states (Arizona, California, Florida, New York, and Texas) and focuses on 15 MAHC elements deemed critical to minimizing the risk for illness and injury associated with aquatic facilities (e.g., disinfection to prevent transmission of infectious pathogens, safety equipment to rescue distressed bathers, and pool chemical safety). Although these data (the first and most recent that are available) are not nationally representative, 15.7% of the estimated 309,000 U.S. public aquatic venues are located in the 16 reporting jurisdictions. RESULTS: During 2013, environmental health practitioners in the 16 reporting NAFIS jurisdictions conducted 84,187 routine inspections of 48,632 public aquatic venues. Of the 84,187 routine inspection records for individual aquatic venues, 78.5% (66,098) included data on immediate closure; 12.3% (8,118) of routine inspections resulted in immediate closure because of at least one identified violation that represented a serious threat to public health. Disinfectant concentration violations were identified during 11.9% (7,662/64,580) of routine inspections, representing risk for aquatic facility-associated outbreaks of infectious etiology. Safety equipment violations were identified during 12.7% (7,845/61,648) of routine inspections, representing risk for drowning. Pool chemical safety violations were identified during 4.6% (471/10,264) of routine inspections, representing risk for pool chemical associated health events. INTERPRETATION: Routine inspections frequently resulted in immediate closure and identified violations of inspection items corresponding to 15 MAHC elements critical to protecting public health, highlighting the need to improve operation and maintenance of U.S. public aquatic facilities. These findings also underscore the public health function that code enforcement, conducted by environmental health practitioners, has in preventing illness and injury at public aquatic facilities. PUBLIC HEALTH ACTION: Findings from the routine analyses of aquatic facility inspection data can inform program planning, implementation, and evaluation. At the state and local level, these inspection data can be used to identify aquatic facilities and venues in need of more frequent inspections and to select topics to cover in training for aquatic facility operators. At the national level, these data can be used to evaluate whether the adoption of MAHC elements minimizes the risk for aquatic facility associated illness and injury. These findings also can be used to prioritize revisions or updates to the MAHC. To optimize the collection and analysis of aquatic facility inspection data and thus application of findings, environmental health practitioners and epidemiologists need to collaborate extensively to identify public aquatic facility code elements deemed critical to protecting public health and determine the best way to assess and document compliance during inspections. PMID- 27199096 TI - Toward a science of morality: response to Christian Miller's critique. AB - In developing a science of morality, many examples are provided not only to document the moral progress that has been made over the centuries, but also the reasons why and how this progress has been made. Instead of moralizing about human action and social problems that we find deplorable or undesirable, ever since the Scientific Revolution and the Enlightenment we started seeing them as problems to be solved. A science of morality begins with the discovery of rights and other moral values and emotions, starting with the recognition of the individual as an autonomous moral agent with an evolved natural desire to survive and flourish. PMID- 27199097 TI - ESSCA results with the baseline series, 2002-2012: p-phenylenediamine. AB - BACKGROUND: Allergic contact dermatitis caused by p-phenylenediamine (PPD) is common among all age groups and both sexes. Monitoring of prevalence and intensity of sensitization is important. OBJECTIVE: To evaluate contact allergy to PPD in Europe, and to compare reaction intensities in different European regions. METHODS: Data collected by the European Surveillance System on Contact Allergies (ESSCA) network between 2002 and 2012 from 12 European countries were analysed regarding prevalence, grading of positive reactions to PPD, and relevance. RESULTS: A total of 99 926 PPD-positive patients from 63 departments were included for analysis. The overall (2002-2012) prevalence of PPD sensitization in Europe is ~4%. Stratified for country, the highest overall standardized prevalence was found in Lithuania, and the lowest in Slovenia. The prevalence of PPD sensitization did not decline over the years. In the southern European countries, higher numbers of strong and extremely strong reactions were registered. The clinical relevance of PPD sensitization varied from half to three quarters. CONCLUSION: The prevalence of PPD sensitization has not changed over time. Strong and extremely strong patch test reactions are seen more often in the South, probably because of the higher number of PPD-containing hair dye products. PMID- 27199098 TI - Decoupled form and function in disparate herbivorous dinosaur clades. AB - Convergent evolution, the acquisition of morphologically similar traits in unrelated taxa due to similar functional demands or environmental factors, is a common phenomenon in the animal kingdom. Consequently, the occurrence of similar form is used routinely to address fundamental questions in morphofunctional research and to infer function in fossils. However, such qualitative assessments can be misleading and it is essential to test form/function relationships quantitatively. The parallel occurrence of a suite of morphologically convergent craniodental characteristics in three herbivorous, phylogenetically disparate dinosaur clades (Sauropodomorpha, Ornithischia, Theropoda) provides an ideal test case. A combination of computational biomechanical models (Finite Element Analysis, Multibody Dynamics Analysis) demonstrate that despite a high degree of morphological similarity between representative taxa (Plateosaurus engelhardti, Stegosaurus stenops, Erlikosaurus andrewsi) from these clades, their biomechanical behaviours are notably different and difficult to predict on the basis of form alone. These functional differences likely reflect dietary specialisations, demonstrating the value of quantitative biomechanical approaches when evaluating form/function relationships in extinct taxa. PMID- 27199099 TI - Ultrahigh-Power-Factor Carbon Nanotubes and an Ingenious Strategy for Thermoelectric Performance Evaluation. AB - An ingenious strategy is put forward to evaluate accurately the thermoelectric performance of carbon nanotube (CNT) thin films, including thermal conductivity, electrical conductivity, and Seebeck coefficient in the same direction. The results reveal that the as-prepared CNT interconnected films and CNT fibers possess enormous potential of thermoelectric applications because of their ultrahigh power factors. PMID- 27199100 TI - Preexposure Prophylaxis Modality Preferences Among Men Who Have Sex With Men and Use Social Media in the United States. AB - BACKGROUND: Preexposure prophylaxis (PrEP) is available as a daily pill for preventing infection with the human immunodeficiency virus (HIV). Innovative methods of administering PrEP systemically or topically are being discussed and developed. OBJECTIVE: The objective of our study was to assess attitudes toward different experimental modalities of PrEP administration. METHODS: From April to July 2015, we recruited 1106 HIV-negative men who have sex with men through online social media advertisements and surveyed them about their likelihood of using different PrEP modalities. Participants responded to 5-point Likert-scale items indicating how likely they were to use each of the following PrEP modalities: a daily oral pill, on-demand pills, periodic injection, penile gel (either before or after intercourse), rectal gel (before/after), and rectal suppository (before/after). We used Wilcoxon signed rank tests to determine whether the stated likelihood of using any modality differed from daily oral PrEP. Related items were combined to assess differences in likelihood of use based on tissue or time of administration. Participants also ranked their interest in using each modality, and we used the modified Borda count method to determine consensual rankings. RESULTS: Most participants indicated they would be somewhat likely or very likely to use PrEP as an on-demand pill (685/1105, 61.99%), daily oral pill (528/1036, 50.97%), injection (575/1091, 52.70%), or penile gel (438/755, 58.01% before intercourse; 408/751, 54.33% after). The stated likelihoods of using on-demand pills (median score 4) and of using a penile gel before intercourse (median 4) were both higher than that of using a daily oral pill (median 4, P<.001 and P=.001, respectively). Compared with a daily oral pill, participants reported a significantly lower likelihood of using any of the 4 rectal modalities (Wilcoxon signed rank test, all P<.001). On 10 point Likert scales created by combining application methods, the reported likelihood of using a penile gel (median 7) was higher than that of using a rectal gel (median 6, P<.001), which was higher than the likelihood of using a rectal suppository (median 6, P<.001). The modified Borda count ranked on-demand pills as the most preferred modality. There was no difference in likelihood of use of PrEP (gel or suppository) before or after intercourse. CONCLUSIONS: Participants typically prefer systemic PrEP and are less likely to use a modality that is administered rectally. Although most of these modalities are seen as favorable or neutral, attitudes may change as information about efficacy and application becomes available. Further data on modality preference across risk groups will better inform PrEP development. PMID- 27199101 TI - A multi-ingredient dietary supplement abolishes large-scale brain cell loss, improves sensory function, and prevents neuronal atrophy in aging mice. AB - Transgenic growth hormone mice (TGM) are a recognized model of accelerated aging with characteristics including chronic oxidative stress, reduced longevity, mitochondrial dysfunction, insulin resistance, muscle wasting, and elevated inflammatory processes. Growth hormone/IGF-1 activate the Target of Rapamycin known to promote aging. TGM particularly express severe cognitive decline. We previously reported that a multi-ingredient dietary supplement (MDS) designed to offset five mechanisms associated with aging extended longevity, ameliorated cognitive deterioration and significantly reduced age-related physical deterioration in both normal mice and TGM. Here we report that TGM lose more than 50% of cells in midbrain regions, including the cerebellum and olfactory bulb. This is comparable to severe Alzheimer's disease and likely explains their striking age-related cognitive impairment. We also demonstrate that the MDS completely abrogates this severe brain cell loss, reverses cognitive decline and augments sensory and motor function in aged mice. Additionally, histological examination of retinal structure revealed markers consistent with higher numbers of photoreceptor cells in aging and supplemented mice. We know of no other treatment with such efficacy, highlighting the potential for prevention or amelioration of human neuropathologies that are similarly associated with oxidative stress, inflammation and cellular dysfunction. Environ. Mol. Mutagen. 57:382-404, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27199102 TI - Epidemiology and use of compression treatment in venous leg ulcers: nationwide claims data analysis in Germany. AB - Chronic venous diseases are the most common causes of leg ulcers. Compression treatment (CT) is a central component of venous leg ulcer (VLU) therapy along with prevention based on guidelines and clinical evidence. However, large-scale data on the use of CT are rare. In particular, there have not yet been published nationwide data for Germany. We analysed data from a large German statutory health insurance (SHI) on incident VLU between 2010 and 2012. VLUs were identified by ICD-10 diagnoses. The status of active disease was defined by wound specific treatments. Compression stockings and bandages were identified by SHI medical device codes. The overall estimated incident rate of active VLU of all insured persons was 0.34% from 2010 to 2012. Adapted to the overall German population, n = 229 369 persons nationwide had an incident VLU in 2010-2012. Among all VLU patients, only 40.6% received CT within 1 year, including 83.3% stockings, 31.8% bandages and 3.1% multi-component compression systems. Compression rates showed significant differences by gender and age. Large regional variations were observed. Validity of data is suggested by high concordance with a primary cohort study. Although recommended by guidelines, there is still a marked under-provision of care, with CT in incident VLUs in Germany requiring active measures. PMID- 27199103 TI - Review article: treatment as prevention - targeting people who inject drugs as a pathway towards hepatitis C eradication. AB - BACKGROUND: Hepatitis C virus (HCV) is a leading cause of chronic liver disease worldwide. HCV predominates in people who inject drugs; a group in whom anti viral therapy has previously been withheld on the basis of chaotic lifestyles and associated risks of reinfection. New research has emerged which suggests that by specifically targeting HCV-infected people who inject drugs for treatment, the pool of HCV would deplete, thus reducing overall transmission and eventually leading to HCV eradication. AIM: To outline the requirements for HCV eradication and review the evidence that this is achievable. METHODS: Expert review of the literature. RESULTS: The achievement of HCV eradication using 'treatment as prevention' is supported by numerous epidemiological modelling studies employing a variety of models in several contexts including people who inject drugs, men who have sex with men and prisoners. More recent studies also incorporate the newer, more efficacious direct-acting anti-viral drugs. These drugs have been shown to be safe and effective in people who inject drugs in clinical trials. There is no empirical evidence of the impact of treatment as prevention strategies on population prevalence. CONCLUSIONS: This review highlights the efforts to control HCV and evaluates the possibilities of achieving eradication of HCV. Currently, the technologies required to achieve HCV eradication exist, but the infrastructure to deliver them is not generally available or of insufficient scale outside of specific areas. Such areas are yet to demonstrate that elimination is possible, but results of studies in these areas are awaited. Such a demonstration would be proof of principle for eradication. Although we are aspiring towards HCV eradication, elimination is the more realistic prospect. PMID- 27199104 TI - Fast Responsive and Controllable Liquid Transport on a Magnetic Fluid/Nanoarray Composite Interface. AB - Controllable liquid transport on surface is expected to occur by manipulating the gradient of surface tension/Laplace pressure and external stimuli, which has been intensively studied on solid or liquid interface. However, it still faces challenges of slow response rate, and uncontrollable transport speed and direction. Here, we demonstrate fast responsive and controllable liquid transport on a smart magnetic fluid/nanoarray interface, i.e., a composite interface, via modulation of an external magnetic field. The wettability of the composite interface to water instantaneously responds to gradient magnetic field due to the magnetically driven composite interface gradient roughness transition that takes place within a millisecond, which is at least 1 order of magnitude faster than that of other responsive surfaces. A water droplet can follow the motion of the gradient composite interface structure as it responds to the gradient magnetic field motion. Moreover, the water droplet transport direction can be controlled by modulating the motion direction of the gradient magnetic field. The composite interface can be used as a pump for the transport of immiscible liquids and other objects in the microchannel, which suggests a way to design smart interface materials and microfluidic devices. PMID- 27199107 TI - Pulsed laser deposited GeTe-rich GeTe-Sb2Te3 thin films. AB - Pulsed laser deposition technique was used for the fabrication of Ge-Te rich GeTe Sb2Te3 (Ge6Sb2Te9, Ge8Sb2Te11, Ge10Sb2Te13, and Ge12Sb2Te15) amorphous thin films. To evaluate the influence of GeTe content in the deposited films on physico-chemical properties of the GST materials, scanning electron microscopy with energy-dispersive X-ray analysis, X-ray diffraction and reflectometry, atomic force microscopy, Raman scattering spectroscopy, optical reflectivity, and sheet resistance temperature dependences as well as variable angle spectroscopic ellipsometry measurements were used to characterize as-deposited (amorphous) and annealed (crystalline) layers. Upon crystallization, optical functions and electrical resistance of the films change drastically, leading to large optical and electrical contrast between amorphous and crystalline phases. Large changes of optical/electrical properties are accompanied by the variations of thickness, density, and roughness of the films due to crystallization. Reflectivity contrast as high as ~0.21 at 405 nm was calculated for Ge8Sb2Te11, Ge10Sb2Te13, and Ge12Sb2Te15 layers. PMID- 27199108 TI - [3 + 1]- and [3 + 2]-Cycloadditions of Azaoxyallyl Cations and Sulfur Ylides. AB - A new formal [3 + 1]-cycloaddition reaction of azaoxyallyl cation intermediates, generated in situ from alpha-halo hydroxamates bearing alpha-alkyl groups, and sulfur ylides is reported, furnishing useful beta-lactams (dr >19:1) in fair to modest yields. In contrast, an unexpected formal [3 + 2]-cycloaddition reaction occurs to give gamma-lactam derivatives for alpha-halo hydroxamates with alpha aryl groups and sulfur ylides in the presence of bases. PMID- 27199109 TI - Open surgery versus stent placement in failed primary surgical treatment of esophageal perforation - a single institutional experience. AB - BACKGROUND: Surgical treatment is an accepted method to manage esophageal perforation, but in many cases it may result in failure. This paper compares the efficacy of surgical treatment and stenting in patients after previous surgical intervention for esophageal perforation. METHODS: A single-institution retrospective study was performed in a group of patients treated for esophageal perforation admitted to our centre from 2010 to 2015. Seventy eight patients (76.5%) with esophageal perforation received surgical treatment. In this group of patients, the mean time between perforation and treatment was 80.6 h (24-240 h). Spontaneous and iatrogenic perforation was observed in 33 (42.3%) and 45 (57.7%) patients, respectively. Partial esophageal resection was performed in 11 cases (14.1%). The perforation site was sutured in the remaining 67 patients (85.9%). Surgical treatment failed in 29 cases (37.2%). RESULTS: In patients with failed previous surgical treatment, revision surgery was performed in 14 patients (48.3%) (group A), and a large-diameter self-expandable stent was implanted in 15 cases (51.7%) (group B). Perforation in the thoracic and distal esophagus was observed in 5 (35.7%) and 9 (64.3%) patients from group A, and in 7 (46.7%) and 8 (53.3%) patients from group B, respectively. The mean intubation time in both groups was 30.3 and 12.5 days (p < 0.001), respectively. The mean daily drainage within five days after the intervention was 350 mL in group A, and 500 mL in group B (p < 0.02). In both groups hospitalisation time was 41.5 and 19.4 days, respectively (p < 0.001). Six patients died (42.8%) following revision surgery, and 2 (13.3%) patients died after stent implantation (p < 0.001). CONCLUSIONS: Intubation time, hospitalization, and the rate of fatal complications in patients who underwent stent implantations were significantly lower compared to reoperated patients; however, the rate of prolonged drainage was lower in patients who underwent revision surgery. In conclusion, stent implantation is a significantly superior method to treat persistent leakage following failure of previous surgical treatment. PMID- 27199110 TI - Paternal Caregivers' Parenting Practices and Psychological Functioning among African American Youth Living in Urban Public Housing. AB - Structural factors associated with public housing contribute to living environments that expose families to adverse life events that may in turn directly impact parenting and youth outcomes. However, despite the growth in research on fathers, research on families in public housing has practically excluded fathers and the role fathers play in the well-being of their adolescents. Using a sample of 660 African American adolescents recruited from public housing, we examined the relationship between paternal caregivers' (i.e., fathers' and father figures') parenting practices and adolescents' depressive symptoms, attitudes toward deviance, and self-efficacy. Using a latent profile analysis (LPA), we confirmed a four-class model of paternal parenting practices ranging from high to low levels of monitoring and encouragement. Results from a one-way ANOVA indicated that paternal caregivers with high (compared to moderate) levels of encouragement and monitoring were associated with youth who reported less depressive symptoms, higher levels of self-efficacy, and less favorable attitudes toward deviance. Discriminant analysis results indicated that approximately half of the sample were correctly classified into two paternal caregiver classes. The findings provide evidence that some of these caregivers engage in parenting practices that support youths' psychological functioning. More research is needed to determine what accounts for the variability in levels of paternal encouragement and supervision, including environmental influences, particularly for paternal caregivers exhibiting moderate-to-low levels of paternal encouragement and monitoring. PMID- 27199112 TI - Females have greater left ventricular twist mechanics than males during acute reductions to preload. AB - Compared to males, females have smaller left ventricular (LV) dimensions and volumes, higher ejection fractions (EF), and higher LV longitudinal and circumferential strain. LV twist mechanics determine ventricular function and are preload-dependent. Therefore, the sex differences in LV structure and myocardial function may result in different mechanics when preload is altered. This study investigated sex differences in LV mechanics during acute challenges to preload. With the use of conventional and speckle-tracking echocardiography, LV structure and function were assessed in 20 males (24 +/- 6.2 yr) and 20 females (23 +/- 3.1 yr) at baseline and during progressive levels of lower body negative pressure (LBNP). Fourteen participants (8 males, 6 females) were also assessed following a rapid infusion of saline. LV end-diastolic volume, end-systolic volume, stroke volume (SV), and EF were reduced in both groups during LBNP (P < 0.001). While males had greater absolute volumes (P < 0.001), there were no sex differences in allometrically scaled volumes at any stage. Sex differences were not detected at baseline in basal rotation, apical rotation, or twist. Apical rotation and twist increased in both groups (P < 0.001) with LBNP. At -60 mmHg, females had greater apical rotation (P = 0.009), twist (P = 0.008), and torsion (P = 0.002) and faster untwisting velocity (P = 0.02) than males. There were no differences in mechanics following saline infusion. Females have larger LV twist and a faster untwisting velocity than males during large reductions to preload, supporting that females have a greater reliance on LV twist mechanics to maintain SV during severe reductions to preload. PMID- 27199113 TI - Microvascular endothelial cells from preeclamptic women exhibit altered expression of angiogenic and vasopressor factors. AB - Preeclampsia (PE) is a severe complication of pregnancy associated with maternal and fetal morbidity and mortality. The underlying pathophysiology involves maternal systemic vascular and endothelial dysfunction associated with circulating antiangiogenic factors, although the specific etiology of the disease remains elusive. Our aim was to investigate the maternal endothelium in PE by exploring the expression of genes involved with endothelial function in a novel platform of maternal primary endothelial cells. Adipose tissue was sampled at the time of caesarean section from both normal and preeclamptic patients. Maternal microvascular endothelial cells were isolated by tissue digestion and CD31 magnetic Dynabeads. Cell purity was confirmed by immunofluorescence microscopy and flow cytometry. Western analyses revealed VEGF activation of VEGF receptor 2 (VEGFR2) and ERK in primary cells. Quantitative PCR analyses revealed significantly altered mRNA levels of various genes involved with angiogenesis and blood pressure control in preeclamptic cells, including soluble fms-like tyrosine kinase-1, endoglin, VEGFR2, angiotensin receptor 1, and endothelin compared with cells isolated from normal pregnancies. Overall, maternal endothelial cells from preeclamptic patients exhibit extensive alteration of expression of factors associated with antiangiogenic and vasoconstrictive phenotypes, shedding light on the underlying mechanisms associated with the vascular dysfunction characteristic of PE. PMID- 27199111 TI - Discordant signaling and autophagy response to fasting in hearts of obese mice: Implications for ischemia tolerance. AB - Autophagy is regulated by nutrient and energy status and plays an adaptive role during nutrient deprivation and ischemic stress. Metabolic syndrome (MetS) is a hypernutritive state characterized by obesity, dyslipidemia, elevated fasting blood glucose levels, and insulin resistance. It has also been associated with impaired autophagic flux and larger-sized infarcts. We hypothesized that diet induced obesity (DIO) affects nutrient sensing, explaining the observed cardiac impaired autophagy. We subjected male friend virus B NIH (FVBN) mice to a high fat diet, which resulted in increased weight gain, fat deposition, hyperglycemia, insulin resistance, and larger infarcts after myocardial ischemia-reperfusion. Autophagic flux was impaired after 4 wk on a high-fat diet. To interrogate nutrient-sensing pathways, DIO mice were subjected to overnight fasting, and hearts were processed for biochemical and proteomic analysis. Obese mice failed to upregulate LC3-II or to clear p62/SQSTM1 after fasting, although mRNA for LC3B and p62/SQSTM1 were appropriately upregulated in both groups, demonstrating an intact transcriptional response to fasting. Energy- and nutrient-sensing signal transduction pathways [AMPK and mammalian target of rapamycin (mTOR)] also responded appropriately to fasting, although mTOR was more profoundly suppressed in obese mice. Proteomic quantitative analysis of the hearts under fed and fasted conditions revealed broad changes in protein networks involved in oxidative phosphorylation, autophagy, oxidative stress, protein homeostasis, and contractile machinery. In many instances, the fasting response was quite discordant between lean and DIO mice. Network analysis implicated the peroxisome proliferator-activated receptor and mTOR regulatory nodes. Hearts of obese mice exhibited impaired autophagy, altered proteome, and discordant response to nutrient deprivation. PMID- 27199114 TI - Physiological levels of thrombospondin-1 decrease NO-dependent vasodilation in coronary microvessels from aged rats. AB - Aging and cardiovascular disease are associated with the loss of nitric oxide (NO) signaling and a decline in the ability to increase coronary blood flow reserve (CFR). Thrombospondin-1 (Thbs-1), through binding of CD47, has been shown to limit NO-dependent vasodilation in peripheral vascular beds via formation of superoxide (O2 (-)). The present study tests the hypothesis that, similar to the peripheral vasculature, blocking CD47 will improve NO-mediated vasoreactivity in coronary arterioles from aged individuals, resulting in improved CFR. Isolated coronary arterioles from young (4 mo) or old (24 mo) female Fischer 344 rats were challenged with the NO donor, DEA-NONO-ate (1 * 10(-7) to 1 * 10(-4) M), and vessel relaxation and O2 (-) production was measured before and after Thbs-1, alphaCD47, and/or Tempol and catalase exposure. In vivo CFR was determined in anesthetized rats (1-3% isoflurane-balance O2) via injected microspheres following control IgG or alphaCD47 treatment (45 min). Isolated coronary arterioles from young and old rats relax similarly to exogenous NO, but addition of 2.2 nM Thbs-1 inhibited NO-mediated vasodilation by 24% in old rats, whereas young vessels were unaffected. Thbs-1 increased O2 (-) production in coronary arterioles from rats of both ages, but this was exaggerated in old rats. The addition of CD47 blocking antibody completely restored NO-dependent vasodilation in isolated arterioles from aged rats and attenuated O2 (-) production. Furthermore, alphaCD47 treatment increased CFR from 9.6 +/- 9.3 (IgG) to 84.0 +/- 23% in the left ventricle in intact, aged animals. These findings suggest that the influence of Thbs-1 and CD47 on coronary perfusion increases with aging and may be therapeutically targeted to reverse coronary microvascular dysfunction. PMID- 27199115 TI - Distinct right ventricle remodeling in response to pressure overload in the rat. AB - Pulmonary arterial hypertension (PAH), the most serious chronic disorder of the pulmonary circulation, is characterized by pulmonary vasoconstriction and remodeling, resulting in increased afterload on the right ventricle (RV). In fact, RV function is the main determinant of prognosis in PAH. The most frequently used experimental models of PAH include monocrotaline- and chronic hypoxia-induced PAH, which primarily affect the pulmonary circulation. Alternatively, pulmonary artery banding (PAB) can be performed to achieve RV overload without affecting the pulmonary vasculature, allowing researchers to determine the RV-specific effects of their drugs/interventions. In this work, using two different degrees of pulmonary artery constriction, we characterize, in full detail, PAB-induced adaptive and maladaptive remodeling of the RV at 3 wk after PAB surgery. Our results show that application of a mild constriction resulted in adaptive hypertrophy of the RV, with preserved systolic and diastolic function, while application of a severe constriction resulted in maladaptive hypertrophy, with chamber dilation and systolic and diastolic dysfunction up to the isolated cardiomyocyte level. By applying two different degrees of constriction, we describe, for the first time, a reliable and short-duration PAB model in which RV adaptation can be distinguished at 3 wk after surgery. We characterize, in full detail, structural and functional changes of the RV in its response to moderate and severe constriction, allowing researchers to better study RV physiology and transition to dysfunction and failure, as well as to determine the effects of new therapies. PMID- 27199116 TI - Simultaneous exposure to nitric oxide inhibition and angiotensin II overload: is it a murine model of mitochondrial dysfunction in nonischemic heart failure? PMID- 27199117 TI - The endothelial glycocalyx promotes homogenous blood flow distribution within the microvasculature. AB - Many common diseases involve impaired tissue perfusion, and heterogeneous distribution of blood flow in the microvasculature contributes to this pathology. The physiological mechanisms regulating homogeneity/heterogeneity of microvascular perfusion are presently unknown. Using established empirical formulations for blood viscosity modeling in vivo (blood vessels) and in vitro (glass tubes), we showed that the in vivo formulation predicts more homogenous perfusion of microvascular networks at the arteriolar and capillary levels. Next, we showed that the more homogeneous blood flow under simulated in vivo conditions can be explained by changes in red blood cell interactions with the vessel wall. Finally, we demonstrated that the presence of a space-filling, semipermeable layer (such as the endothelial glycocalyx) at the vessel wall can account for the changes of red blood cell interactions with the vessel wall that promote homogenous microvascular perfusion. Collectively, our results indicate that the mechanical properties of the endothelial glycocalyx promote homogeneous microvascular perfusion. Preservation or restoration of normal glycocalyx properties may be a viable strategy for improving tissue perfusion in a variety of diseases. PMID- 27199118 TI - TXNIP regulates myocardial fatty acid oxidation via miR-33a signaling. AB - Myocardial fatty acid beta-oxidation is critical for the maintenance of energy homeostasis and contractile function in the heart, but its regulation is still not fully understood. While thioredoxin-interacting protein (TXNIP) has recently been implicated in cardiac metabolism and mitochondrial function, its effects on beta-oxidation have remained unexplored. Using a new cardiomyocyte-specific TXNIP knockout mouse and working heart perfusion studies, as well as loss- and gain-of function experiments in rat H9C2 and human AC16 cardiomyocytes, we discovered that TXNIP deficiency promotes myocardial beta-oxidation via signaling through a specific microRNA, miR-33a. TXNIP deficiency leads to increased binding of nuclear factor Y (NFYA) to the sterol regulatory element binding protein 2 (SREBP2) promoter, resulting in transcriptional inhibition of SREBP2 and its intronic miR-33a. This allows for increased translation of the miR-33a target genes and beta-oxidation-promoting enzymes, carnitine octanoyl transferase (CROT), carnitine palmitoyl transferase 1 (CPT1), hydroxyacyl-CoA dehydrogenase/3 ketoacyl-CoA thiolase/enoyl-CoA hydratase-beta (HADHB), and AMPKalpha and is associated with an increase in phospho-AMPKalpha and phosphorylation/inactivation of acetyl-CoA-carboxylase. Thus, we have identified a novel TXNIP-NFYA-SREBP2/miR 33a-AMPKalpha/CROT/CPT1/HADHB pathway that is conserved in mouse, rat, and human cardiomyocytes and regulates myocardial beta-oxidation. PMID- 27199119 TI - A myosin activator improves actin assembly and sarcomere function of human induced pluripotent stem cell-derived cardiomyocytes with a troponin T point mutation. AB - We have investigated cardiac myocytes derived from human-induced pluripotent stem cells (iPSC-CMs) from two normal control and two family members expressing a mutant cardiac troponin T (cTnT-R173W) linked to dilated cardiomyopathy (DCM). cTnT is a regulatory protein of the sarcomeric thin filament. The loss of this basic charge, which is strategically located to control tension, has consequences leading to progressive DCM. iPSC-CMs serve as a valuable platform for understanding clinically relevant mutations in sarcomeric proteins; however, there are important questions to be addressed with regard to myocyte adaptation that we model here by plating iPSC-CMs on softer substrates (100 kPa) to create a more physiologic environment during recovery and maturation of iPSC-CMs after thawing from cryopreservation. During the first week of culture of the iPSC-CMs, we have determined structural and functional characteristics as well as actin assembly dynamics. Shortening, actin content, and actin assembly dynamics were depressed in CMs from the severely affected mutant at 1 wk of culture, but by 2 wk differences were less apparent. Sarcomeric troponin and myosin isoform composition were fetal/neonatal. Furthermore, the troponin complex, reconstituted with wild-type cTnT or recombinant cTnT-R173W, depressed the entry of cross bridges into the force-generating state, which can be reversed by the myosin activator omecamtiv mecarbil. Therapeutic doses of this drug increased both contractility and the content of F-actin in the mutant iPSC-CMs. Collectively, our data suggest the use of a myosin activation reagent to restore function within patient-specific iPSC-CMs may aid in understanding and treating this familial DCM. PMID- 27199120 TI - Matrix metalloproteinase-2 in oncostatin M-induced sarcomere degeneration in cardiomyocytes. AB - Cardiomyocyte dedifferentiation may be an important source of proliferating cardiomyocytes facilitating cardiac repair. Cardiomyocyte dedifferentiation and proliferation induced by oncostatin-M (OSM) is characterized by sarcomere degeneration. However, the mechanism underlying sarcomere degeneration remains unclear. We hypothesized that this process may involve matrix metalloproteinase-2 (MMP-2), a key protease localized at the sarcomere in cardiomyocytes. We tested the hypothesis that MMP-2 is involved in the sarcomere degeneration that characterizes cardiomyocyte dedifferentiation. Confocal immunofluorescence and biochemical methods were used to explore the role of MMP-2 in OSM-induced dedifferentiation of neonatal rat ventricular myocytes (NRVM). OSM caused a concentration- and time-dependent loss of sarcomeric alpha-actinin and troponin-I in NRVM. Upon OSM-treatment, the mature sarcomere transformed to a phenotype resembling a less-developed sarcomere, i.e., loss of sarcomeric proteins and Z disk transformed into disconnected Z bodies, characteristic of immature myofibrils. OSM dose dependently increased MMP-2 activity. Both the pan-MMP inhibitor GM6001 and the selective MMP-2 inhibitor ARP 100 prevented sarcomere degeneration induced by OSM treatment. OSM also induced NRVM cell cycling and increased methyl-thiazolyl-tetrazolium (MTT) staining, preventable by MMP inhibition. These results suggest that MMP-2 mediates sarcomere degeneration in OSM-induced cardiomyocyte dedifferentiation and thus potentially contributes to cardiomyocyte regeneration. PMID- 27199122 TI - Recycling KATP channels for cardioprotection. PMID- 27199121 TI - Differential effects of nebivolol vs. metoprolol on microvascular function in hypertensive humans. AB - Use of beta-adrenergic receptor (AR) blocker is associated with increased risk of fatigue and exercise intolerance. Nebivolol is a newer generation beta-blocker, which is thought to avoid this side effect via its vasodilating property. However, the effects of nebivolol on skeletal muscle perfusion during exercise have not been determined in hypertensive patients. Accordingly, we performed contrast-enhanced ultrasound perfusion imaging of the forearm muscles in 25 untreated stage I hypertensive patients at rest and during handgrip exercise at baseline or after 12 wk of treatment with nebivolol (5-20 mg/day) or metoprolol succinate (100-300 mg/day), with a subsequent double crossover for 12 wk. Metoprolol and nebivolol each induced a reduction in the resting blood pressure and heart rate (130.9 +/- 2.6/81.7 +/- 1.8 vs. 131.6 +/- 2.7/80.8 +/- 1.5 mmHg and 63 +/- 2 vs. 64 +/- 2 beats/min) compared with baseline (142.1 +/- 2.0/88.7 +/- 1.4 mmHg and 75 +/- 2 beats/min, respectively, both P < 0.01). Metoprolol significantly attenuated the increase in microvascular blood volume (MBV) during handgrip at 12 and 20 repetitions/min by 50% compared with baseline (mixed-model P < 0.05), which was not observed with nebivolol. Neither metoprolol nor nebivolol affected microvascular flow velocity (MFV). Similarly, metoprolol and nebivolol had no effect on the increase in the conduit brachial artery flow as determined by duplex Doppler ultrasound. Thus our study demonstrated a first direct evidence for metoprolol-induced impairment in the recruitment of microvascular units during exercise in hypertensive humans, which was avoided by nebivolol. This selective reduction in MBV without alteration in MFV by metoprolol suggested impaired vasodilation at the precapillary arteriolar level. PMID- 27199123 TI - Guanylyl cyclase can't stand the HETE. PMID- 27199124 TI - Sex dimorphisms of crossbridge cycling kinetics in transgenic hypertrophic cardiomyopathy mice. AB - Familial hypertrophic cardiomyopathy (HCM) is a disease of the sarcomere and may lead to hypertrophic, dilated, restrictive, and/or arrhythmogenic cardiomyopathy, congestive heart failure, or sudden cardiac death. We hypothesized that hearts from transgenic HCM mice harboring a mutant myosin heavy chain increase the energetic cost of contraction in a sex-specific manner. To do this, we assessed Ca(2+) sensitivity of tension and crossbridge kinetics in demembranated cardiac trabeculas from male and female wild-type (WT) and HCM hearts at an early time point (2 mo of age). We found a significant effect of sex on Ca(2+) sensitivity such that male, but not female, HCM mice displayed a decrease in Ca(2+) sensitivity compared with WT counterparts. The HCM transgene and sex significantly impacted the rate of force redevelopment by a rapid release restretch protocol and tension cost by the ATPase-tension relationship. In each of these measures, HCM male trabeculas displayed a gain-of-function when compared with WT counterparts. In addition, cardiac remodeling measured by echocardiography, histology, morphometry, and posttranslational modifications demonstrated sex- and HCM-specific effects. In conclusion, female and male HCM mice display sex dimorphic crossbridge kinetics accompanied by sex- and HCM dependent cardiac remodeling at the morphometric, histological, and cellular level. PMID- 27199125 TI - Disrupted NOS signaling in lymphatic endothelial cells exposed to chronically increased pulmonary lymph flow. AB - Associated abnormalities of the lymphatic circulation are well described in congenital heart disease. However, their mechanisms remain poorly elucidated. Using a clinically relevant ovine model of a congenital cardiac defect with chronically increased pulmonary blood flow (shunt), we previously demonstrated that exposure to chronically elevated pulmonary lymph flow is associated with: 1) decreased bioavailable nitric oxide (NO) in pulmonary lymph; and 2) attenuated endothelium-dependent relaxation of thoracic duct rings, suggesting disrupted lymphatic endothelial NO signaling in shunt lambs. To further elucidate the mechanisms responsible for this altered NO signaling, primary lymphatic endothelial cells (LECs) were isolated from the efferent lymphatic of the caudal mediastinal node in 4-wk-old control and shunt lambs. We found that shunt LECs (n = 3) had decreased bioavailable NO and decreased endothelial nitric oxide synthase (eNOS) mRNA and protein expression compared with control LECs (n = 3). eNOS activity was also low in shunt LECs, but, interestingly, inducible nitric oxide synthase (iNOS) expression and activity were increased in shunt LECs, as were total cellular nitration, including eNOS-specific nitration, and accumulation of reactive oxygen species (ROS). Pharmacological inhibition of iNOS reduced ROS in shunt LECs to levels measured in control LECs. These data support the conclusion that NOS signaling is disrupted in the lymphatic endothelium of lambs exposed to chronically increased pulmonary blood and lymph flow and may contribute to decreased pulmonary lymphatic bioavailable NO. PMID- 27199128 TI - High-throughput drug profiling with voltage- and calcium-sensitive fluorescent probes in human iPSC-derived cardiomyocytes. AB - Cardiomyocytes derived from human embryonic stem cells (hESCs) or induced pluripotent stem cells (hiPSCs) are increasingly used for in vitro assays and represent an interesting opportunity to increase the data throughput for drug development. In this work, we describe a 96-well recording of synchronous electrical activities from spontaneously beating hiPSC-derived cardiomyocyte monolayers. The signal was obtained with a fast-imaging plate reader using a submillisecond-responding membrane potential recording assay, FluoVolt, based on a newly derived voltage-sensitive fluorescent dye. In our conditions, the toxicity of the dye was moderate and compatible with episodic recordings for >3 h. We show that the waveforms recorded from a whole well or from a single cell sized zone are equivalent and make available critical functional parameters that are usually accessible only with gold standard techniques like intracellular microelectrode recording. This approach allows accurate identification of the electrophysiological effects of reference drugs on the different phases of the cardiac action potential as follows: fast depolarization (lidocaine), early repolarization (nifedipine, Bay K8644, and veratridine), late repolarization (dofetilide), and diastolic slow depolarization (ivabradine). Furthermore, the data generated with the FluoVolt dye can be pertinently complemented with a calcium-sensitive dye for deeper characterization of the pharmacological responses. In a semiautomated plate reader, the two probes used simultaneously in 96-well plates provide an easy and powerful multiparametric assay to rapidly and precisely evaluate the cardiotropic profile of compounds for drug discovery or cardiac safety. PMID- 27199127 TI - The contributions of dipeptidyl peptidase IV to inflammation in heart failure. AB - Circulating dipeptidyl peptidase IV (DPPIV) activity correlates with cardiac dysfunction in humans and experimental heart failure (HF) models. Similarly, inflammatory markers are associated with poorer outcomes in HF patients. However, the contributions of DPPIV to inflammation in HF remain elusive. Therefore, this study aimed to investigate whether the cardioprotective effects of DPPIV inhibition after myocardial injury are accompanied by reduced cardiac inflammation, whether circulating DPPIV activity correlates with the levels of systemic inflammatory markers in HF patients, and whether leukocytes and/or splenocytes may be one of the sources of circulating DPPIV in HF. Experimental HF was induced in male Wistar rats by left ventricular myocardial injury after radiofrequency catheter ablation. The rats were divided into three groups: sham, HF, and HF + DPPIV inhibitor (sitagliptin). Six weeks after surgery, cardiac function, perfusion and inflammatory status were evaluated. Sitagliptin treatment improved cardiac function and perfusion, reduced macrophage infiltration, and diminished the levels of inflammatory biomarkers including TNF-alpha, IL-1beta, and CCL2. In HF patients, serum DPPIV activity correlated with CCL2, suggesting that leukocytes may be the source of circulating DPPIV in HF. Unexpectedly, DPPIV release was higher in splenocytes from HF rats and similar in HF circulating mononuclear cells compared with those from sham, suggesting an organ-specific modulation of DPPIV in HF. Collectively, our data provide new evidence that the cardioprotective effects of DPPIV inhibition in HF may be due to suppression of inflammatory cytokines. Moreover, they suggest that a vicious circle between DPPIV and inflammation may contribute to HF development and progression. PMID- 27199126 TI - Selective downregulation of mitochondrial electron transport chain activity and increased oxidative stress in human atrial fibrillation. AB - Mitochondria are critical for maintaining normal cardiac function, and a deficit in mitochondrial energetics can lead to the development of the substrate that promotes atrial fibrillation (AF) and its progression. However, the link between mitochondrial dysfunction and AF in humans is still not fully defined. The aim of this study was to elucidate differences in the functional activity of mitochondrial oxidative phosphorylation (OXPHOS) complexes and oxidative stress in right atrial tissue from patients without (non-AF) and with AF (AF) who were undergoing open-heart surgery and were not significantly different for age, sex, major comorbidities, and medications. The overall functional activity of the electron transport chain (ETC), NADH:O2 oxidoreductase activity, was reduced by 30% in atrial tissue from AF compared with non-AF patients. This was predominantly due to a selective reduction in complex I (0.06 +/- 0.007 vs. 0.09 +/- 0.006 nmol.min(-1).citrate synthase activity(-1), P = 0.02) and II (0.11 +/- 0.012 vs. 0.16 +/- 0.012 nmol.min(-1).citrate synthase activity(-1), P = 0.003) functional activity in AF patients. Conversely, complex V activity was significantly increased in AF patients (0.21 +/- 0.027 vs. 0.12 +/- 0.01 nmol.min(-1).citrate synthase activity(-1), P = 0.005). In addition, AF patients exhibited a higher oxidative stress with increased production of mitochondrial superoxide (73 +/- 17 vs. 11 +/- 2 arbitrary units, P = 0.03) and 4 hydroxynonenal level (77.64 +/- 30.2 vs. 9.83 +/- 2.83 ng.mg(-1) protein, P = 0.048). Our findings suggest that AF is associated with selective downregulation of ETC activity and increased oxidative stress that can contribute to the progression of the substrate for AF. PMID- 27199129 TI - Impact of high-fat, low-carbohydrate diet on myocardial substrate oxidation, insulin sensitivity, and cardiac function after ischemia-reperfusion. AB - High-fat, low-carbohydrate Diet (HFLCD) impairs the myocardial response to ischemia-reperfusion, but the underlying mechanisms remain elusive. We sought to determine the magnitude of diet-induced alterations in intrinsic properties of the myocardium (including insulin sensitivity and substrate oxidation) and circulating substrate and insulin differences resulting from diet, leading to this impaired response. Rats were fed HFLCD (60% kcal from fat/30% protein/10% carbohydrate) or control diet (CONT) (16%/19%/65%) for 2 wk. Isolated hearts underwent global low-flow ischemia followed by reperfusion (I/R). Carbon-13 NMR spectroscopy was used to determine myocardial substrate TCA cycle entry. Myocardial insulin sensitivity was assessed as dose-response of Akt phosphorylation. There was a significant effect of HFLCD and I/R with both these factors leading to an increase in free fatty acid (FFA) oxidation and a decrease in carbohydrate or ketone oxidation. Following I/R, HFLCD led to decreased ketone and increased FFA oxidation; the recovery of left ventricular (LV) function was decreased in HFLCD and was negatively correlated with FFA oxidation and positively associated with ketone oxidation. HFLCD also resulted in reduced insulin sensitivity. Under physiologic ranges, there were no direct effects of buffer insulin and ketone levels on oxidation of any substrate and recovery of cardiac function after I/R. An insulin-ketone interaction exists for myocardial substrate oxidation characteristics. We conclude that the impaired recovery of function after ischemia-reperfusion with HFLCD is largely due to intrinsic diet effects on myocardial properties, rather than to diet effect on circulating insulin or substrate levels. PMID- 27199132 TI - The alpha11 integrin mediates fibroblast-extracellular matrix-cardiomyocyte interactions in health and disease. AB - Excessive cardiac interstitial fibrosis impairs normal cardiac function. We have shown that the alpha11beta1 (alpha11) integrin mediates fibrotic responses to glycated collagen in rat myocardium by a pathway involving transforming growth factor-beta. Little is known of the role of the alpha11 integrin in the developing mammalian heart. Therefore, we examined the impact of deletion of the alpha11 integrin in wild-type mice and in mice treated with streptozotocin (STZ) to elucidate the role of the alpha11 integrin in normal cardiac homeostasis and in the pathogenesis of diabetes-related fibrosis. As anticipated, cardiac fibrosis was reduced in alpha11 integrin knockout mice (alpha11(-/-); C57BL/6 background) treated with STZ compared with STZ-treated wild-type mice (P < 0.05). Unexpectedly, diastolic function was impaired in both vehicle and STZ-treated alpha11(-/-) mice, as shown by the decreased minimum rate of pressure change and prolonged time constant of relaxation in association with increased end-diastolic pressure (all P < 0.05 compared with wild-type mice). Accordingly, we examined the phenotype of untreated alpha11(-/-) mice, which demonstrated a reduced cardiomyocyte cross-sectional cell area and myofibril thickness (all P < 0.05 compared with wild-type mice) and impaired myofibril arrangement. Immunostaining for desmin and connexin 43 showed abnormal intermediate filament organization at intercalated disks and impaired gap-junction development. Overall, deletion of the alpha11 integrin attenuates cardiac fibrosis in the mammalian mouse heart and reduces ECM formation as a result of diabetes. Furthermore, alpha11 integrin deletion impairs cardiac function and alters cardiomyocyte morphology. These findings shed further light on the poorly understood interaction between the fibroblast-cardiomyocyte and the ECM. PMID- 27199131 TI - Androgen-sensitive hypertension associated with soluble guanylate cyclase-alpha1 deficiency is mediated by 20-HETE. AB - Dysregulated nitric oxide (NO) signaling contributes to the pathogenesis of hypertension, a prevalent and often sex-specific risk factor for cardiovascular disease. We previously reported that mice deficient in the alpha1-subunit of the NO receptor soluble guanylate cyclase (sGCalpha1 (-/-) mice) display sex- and strain-specific hypertension: male but not female sGCalpha1 (-/-) mice are hypertensive on an 129S6 (S6) but not a C57BL6/J (B6) background. We aimed to uncover the genetic and molecular basis of the observed sex- and strain-specific blood pressure phenotype. Via linkage analysis, we identified a suggestive quantitative trait locus associated with elevated blood pressure in male sGCalpha1 (-/-)S6 mice. This locus encompasses Cyp4a12a, encoding the predominant murine synthase of the vasoconstrictor 20-hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE). Renal expression of Cyp4a12a in mice was associated with genetic background, sex, and testosterone levels. In addition, 20-HETE levels were higher in renal preglomerular microvessels of male sGCalpha1 (-/-)S6 than of male sGCalpha1 (-/-)B6 mice. Furthermore, treating male sGCalpha1 (-/-)S6 mice with the 20-HETE antagonist 20-hydroxyeicosa-6(Z),15(Z)-dienoic acid (20-HEDE) lowered blood pressure. Finally, 20-HEDE rescued the genetic background- and testosterone dependent impairment of acetylcholine-induced relaxation in renal interlobar arteries associated with sGCalpha1 deficiency. Elevated Cyp4a12a expression and 20-HETE levels render mice susceptible to hypertension and vascular dysfunction in a setting of sGCalpha1 deficiency. Our data identify Cyp4a12a as a candidate sex-specific blood pressure-modifying gene in the context of deficient NO-sGC signaling. PMID- 27199130 TI - Pregnancy-associated adaptations in [Ca2+]i-dependent and Ca2+ sensitization mechanisms of venous contraction: implications in pregnancy-related venous disorders. AB - Pregnancy is associated with significant adaptations in the maternal hemodynamics and arterial circulation, but the changes in the venous mechanisms during pregnancy are less clear. We hypothesized that pregnancy is associated with alterations in venous function, intracellular free Ca(2+) concentration ([Ca(2+)]i), and Ca(2+)-dependent mechanisms of venous contraction. Circular segments of inferior vena cava (IVC) from virgin and late pregnant (Preg, day 19) Sprague-Dawley rats were suspended between two hooks, labeled with fura-2, and placed in a cuvet inside a spectrofluorometer for simultaneous measurement of contraction and [Ca(2+)]i (fura-2 340/380 ratio). KCl (96 mM), which stimulates Ca(2+) influx, caused less contraction (35.6 +/- 6.3 vs. 92.6 +/- 19.9 mg/mg tissue) and smaller increases in [Ca(2+)]i (1.67 +/- 0.12 vs. 2.19 +/- 0.11) in Preg vs. virgin rat IVC. The alpha-adrenergic receptor agonist phenylephrine (Phe; 10(-5) M) caused less contraction (23.8 +/- 3.4 vs. 70.9 +/- 12.9 mg/mg tissue) and comparable increases in [Ca(2+)]i (1.76 +/- 0.10 vs. 1.89 +/- 0.08) in Preg vs. virgin rat IVC. At increasing extracellular Ca(2+) concentrations ([Ca(2+)]e) (0.1, 0.3, 0.6, 1, and 2.5 mM), KCl and Phe induced [Ca(2+)]e contraction and [Ca(2+)]e-[Ca(2+)]i curves that were reduced in Preg vs. virgin IVC, supporting reduced Ca(2+) entry mechanisms. The [Ca(2+)]e-contraction and [Ca(2+)]e-[Ca(2+)]i curves were used to construct the [Ca(2+)]i-contraction relationship. Despite reduced contraction and [Ca(2+)]i in Preg IVC, the Phe induced [Ca(2+)]i-contraction relationship was greater than that of KCl and was enhanced in Preg vs. virgin IVC, suggesting parallel activation of Ca(2+) sensitization pathways. The Ca(2+) channel blocker diltiazem, protein kinase C (PKC) inhibitor GF-109203X, and Rho-kinase (ROCK) inhibitor Y27632 inhibited KCl- and Phe-induced contraction and abolished the shift in the Phe [Ca(2+)]i contraction relationship in Preg IVC, suggesting an interplay between the decrease in Ca(2+) influx and possible compensatory activation of PKC- and ROCK mediated Ca(2+)-sensitization pathways. The reduced [Ca(2+)]i and [Ca(2+)]i dependent contraction in Preg rat IVC, despite the parallel rescue activation of Ca(2+)-sensitization pathways, suggests that the observed reduction in [Ca(2+)]i dependent contraction mechanisms is likely underestimated, and that the veins without the rescue Ca(2+)-sensitization pathways could be even more prone to dilation during pregnancy. These pregnancy-associated reductions in Ca(2+) entry dependent mechanisms of venous contraction, if occurring in human lower extremity veins and if not adequately compensated by Ca(2+)-sensitization pathways, may play a role in pregnancy-related venous disorders. PMID- 27199135 TI - Influence of anatomical dominance and hypertension on coronary conduit arterial and microcirculatory flow patterns: a multiscale modeling study. AB - Coronary hemodynamics are known to be affected by intravascular and extravascular factors that vary regionally and transmurally between the perfusion territories of left and right coronary arteries. However, despite clinical evidence that left coronary arterial dominance portends greater cardiovascular risk, relatively little is known about the effects of left or right dominance on regional conduit arterial and microcirculatory blood flow patterns, particularly in the presence of systemic or pulmonary hypertension. We addressed this issue using a multiscale numerical model of the human coronary circulation situated in a closed-loop cardiovascular model. The coronary model represented left or right dominant anatomies and accounted for transmural and regional differences in vascular properties and extravascular compression. Regional coronary flow dynamics of the two anatomical variants were compared under normotensive conditions, raised systemic or pulmonary pressures with maintained flow demand, and after accounting for adaptations known to occur in acute and chronic hypertensive states. Key findings were that 1) right coronary arterial flow patterns were strongly influenced by dominance and systemic/pulmonary hypertension; 2) dominance had minor effects on left coronary arterial and all microvascular flow patterns (aside from mean circumflex flow); 3) although systemic hypertension favorably increased perfusion pressure, this benefit varied regionally and transmurally and was offset by increased left ventricular and septal flow demands; and 4) pulmonary hypertension had a substantial negative effect on right ventricular and septal flows, which was exacerbated by greater metabolic demands. These findings highlight the importance of interactions between coronary arterial dominance and hypertension in modulating coronary hemodynamics. PMID- 27199133 TI - Vascular smooth muscle desensitization in rabbit epigastric and mesenteric arteries during hemorrhagic shock. AB - The decompensatory phase of hemorrhage (shock) is caused by a poorly defined phenomenon termed vascular hyporeactivity (VHR). VHR may reflect an acute in vivo imbalance in levels of contractile and relaxant stimuli favoring net vascular smooth muscle (VSM) relaxation. Alternatively, VHR may be caused by intrinsic VSM desensitization of contraction resulting from prior exposure to high levels of stimuli that temporarily adjusts cell signaling systems. Net relaxation, but not desensitization, would be expected to resolve rapidly in an artery segment removed from the in vivo shock environment and examined in vitro in a fresh solution. Our aim was to 1) induce shock in rabbits and apply an in vitro mechanical analysis on muscular arteries isolated pre- and postshock to determine whether VHR involves intrinsic VSM desensitization, and 2) identify whether net VSM relaxation induced by nitric oxide and cyclic nucleotide-dependent protein kinase activation in vitro can be sustained for some time after relaxant stimulus washout. The potencies of phenylephrine- and histamine-induced contractions in in vitro epigastric artery removed from rabbits posthemorrhage were decreased by ~0.3 log units compared with the control contralateral epigastric artery removed prehemorrhage. Moreover, a decrease in KCl-induced tonic, relative to phasic, tension of in vitro mesenteric artery correlated with the degree of shock severity as assessed by rates of lactate and K(+) accumulation. VSM desensitization was also caused by tyramine in vivo and PE in vitro, but not by relaxant agents in vitro. Together, these results support the hypothesis that VHR during hemorrhagic decompensation involves contractile stimulus-induced long lasting, intrinsic VSM desensitization. PMID- 27199137 TI - In vitro thrombogenesis resulting from decreased shear rate and blood coagulability. AB - In vitro antithrombogenic testing with mock circulation is a useful type of pre evaluation in ex vivo testing of mechanical assist devices. For effective in vitro testing, we have been developing a clear quantitative thrombogenesis model based on shear stress and blood coagulability. Bovine blood was used as the test medium. The activating clotting time (ACT) was adjusted with trisodium citrate and calcium chloride from 200 to 1,000 seconds. The blood was then applied to a rheometer and subjected to shear at 50 to 2,880 s-1. Blood coagulation time and degree of thrombogenesis were measured by the torque sensor of the rheometer. Prothrombin time (PT) and activated partial thromboplastin time (APTT) of the test blood were also measured after the application of shear. Blood coagulation time increased, and the degree of thrombogenesis decreased, with increases in shear rate to between 50 and 2,880 s-1. for test bloods with ACTs of 200 to 250 seconds. An ACT of 200 to 250 seconds is thus appropriate for in vitro antithrombogenic testing under a shear rate of 2,880 s-1. APTT was prolonged, whereas PT did not change, with increasing shear rate: that is, increasing the shear rate reduced thrombogenesis related to the intrinsic clotting pathway. An ACT of 200 to 250 seconds was suitable for in vitro antithrombogenic testing, and increasing the shear stress generated in the mechanical assist device reduced thrombogenesis via the intrinsic clotting pathway. PMID- 27199134 TI - Sarcomere neutralization in inherited cardiomyopathy: small-molecule proof-of concept to correct hyper-Ca2+-sensitive myofilaments. AB - The sarcomere is the functional unit of the heart. Alterations in sarcomere activation lead to disease states such as hypertrophic and restrictive cardiomyopathy (HCM/RCM). Mutations in many of the sarcomeric genes are causal for HCM/RCM. In most cases, these mutations result in increased Ca(2+) sensitivity of the sarcomere, giving rise to altered systolic and diastolic function. There is emerging evidence that small-molecule sarcomere neutralization is a potential therapeutic strategy for HCM/RCM. To pursue proof-of-concept, W7 was used here because of its well-known Ca(2+) desensitizer biochemical effects at the level of cardiac troponin C. Acute treatment of adult cardiac myocytes with W7 caused a dose-dependent (1-10 MUM) decrease in contractility in a Ca(2+) independent manner. Alkalosis was used as an in vitro experimental model of acquired heightened Ca(2+) sensitivity, resulting in increased live cell contractility and decreased baseline sarcomere length, which were rapidly corrected with W7. As an inherited cardiomyopathy model, R193H cardiac troponin I (cTnI) transgenic myocytes showed significant decreased baseline sarcomere length and slowed relaxation that were rapidly and dose-dependently corrected by W7. Langendorff whole heart pacing stress showed that R193H cTnI transgenic hearts had elevated end-diastolic pressures at all pacing frequencies compared with hearts from nontransgenic mice. Acute treatment with W7 rapidly restored end diastolic pressures to normal values in R193H cTnI hearts, supporting a sarcomere intrinsic mechanism of dysfunction. The known off-target effects of W7 notwithstanding, these results provide further proof-of-concept that small molecule-based sarcomere neutralization is a potential approach to remediate hyper-Ca(2+)-sensitive sarcomere function. PMID- 27199136 TI - The design of a modular voluntary opening prosthetic hand: ongoing research and preliminary results. AB - INTRODUCTION: This work presents the mechanical design of an artificial hand in order to address the need for a commercially feasible prosthetic hand. METHODS: The hand has 3 compliant fingers and a thumb attached to a reconfigurable palm. The fingers and palm are a novel design, which is based on the natural arches of the hand. The design is modular, minimizing the number of parts and reducing assembly time. RESULTS: This hand and the expandable socket are designed for transradial amputees. It has 9 degrees of freedom (DOFs), 2 of them for the reconfigurable palm. The kinematics and adequate excursion for the fingers and palm are illustrated by finite element method (FEM). CONCLUSIONS: The study implements the mechanical parts by using rapid prototyping to assess preliminary results. PMID- 27199138 TI - About a painful wrist after a forced dorsiflexion trauma. PMID- 27199140 TI - BET 1: Give prehospital blood and save a life? AB - A short cut review was carried out to establish whether prehospital blood transfusion in the trauma patient with active haemorrhage can reduce mortality. 11 directly relevant papers were found using the reported search strategy. Of these two presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. It is concluded that prehospital blood transfusion may reduce short term mortality in these patients, but that the evidence level is low and further definitive randomised controlled trials are needed to prove benefit. PMID- 27199139 TI - A woman with painful lesions of the legs. PMID- 27199142 TI - BET 2: Should real resuscitationists use airway checklists? AB - A short cut review was carried out to establish whether the use of preprocedural checklists prior to intubation of critically ill patients outside a theatre environment can reduce the incidence of adverse events. Four directly relevant papers were found using the reported search strategy and presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. It is concluded that preprocedural checklists may reduce adverse events in these patients, but that the evidence level is low and further matched cohort studies are needed to prove effectiveness. PMID- 27199143 TI - Novosphingobium naphthae sp. nov., from oil-contaminated soil. AB - During the study of hydrocarbon-degrading bacteria in the oil-contaminated soil of Gunsan, North Jeolla Province, South Korea, a light-grey-pigmented, Gram staining-negative, aerobic, non-motile and rod-shaped bacterium, designated strain D39T, was isolated. This strain was non-sporulating, catalase-negative and oxidase-positive. It was able to grow at 12-42 degrees C, pH 5.5-8.5 and with 0 1 % (w/v) NaCl. This strain was characterized taxonomically by a polyphasic approach. Based on the results of 16S rRNA gene sequence analysis, strain D39T belongs to the genus Novosphingobium and is closely related to 'Novosphingobium ginsenosidimutans' FW-6 (97.30 % sequence similarity), Novosphingobium mathurense SM117T (97.17 % sequence similarity) and Novosphingobium aquiterrae E-II-3T (97.01 % sequence similarity). The only respiratory quinone was ubiquinone-10 and the major polyamine was spermidine. The polar lipid profile revealed the presence of phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, sphingoglycolipid and phosphatidyl-N-methylethanolamine. The predominant fatty acids of strain D39T were summed feature 8 (C18 : 1omega7c and/or C18 : 1omega6c), summed feature 3 (C16 : 1omega7c and/or C16 : 1omega6c), C17 : 1omega6c and C14 : 0 2-OH. The genomic DNA G+C content of this novel strain was 66.7 mol%. The DNA-DNA relatedness between strain D39T and 'N. ginsenosidimutans' KACC 16615, N. mathurense KACC 14598T, N. aquiterrae KACC 17599T and Novosphingobium kunmingense DSM 25975T were 33.7 %, 29.0 %, 22.3 % and 18.3 %, respectively. The morphological, physiological, chemotaxonomic and phylogenetic analyses clearly distinguished this strain from its closest phylogenetic neighbours. Thus, strain D39T represents a novel species of the genus Novosphingobium, for which the name Novosphingobium naphthae sp. nov. is proposed. The type strain is D39T (=KEMB 9005-346T=KACC 18593T=JCM 31158T). PMID- 27199145 TI - Selection of asset investment models by hospitals: examination of influencing factors, using Switzerland as an example. AB - Hospitals are responsible for a remarkable part of the annual increase in healthcare expenditure. This article examines one of the major cost drivers, the expenditure for investment in hospital assets. The study, conducted in Switzerland, identifies factors that influence hospitals' investment decisions. A suggestion on how to categorize asset investment models is presented based on the life cycle of an asset, and its influencing factors defined based on transaction cost economics. The influence of five factors (human asset specificity, physical asset specificity, uncertainty, bargaining power, and privacy of ownership) on the selection of an asset investment model is examined using a two-step fuzzy-set Qualitative Comparative Analysis. The research shows that outsourcing-oriented asset investment models are particularly favored in the presence of two combinations of influencing factors: First, if technological uncertainty is high and both human asset specificity and bargaining power of a hospital are low. Second, if assets are very specific, technological uncertainty is high and there is a private hospital with low bargaining power, outsourcing-oriented asset investment models are favored too. Using Qualitative Comparative Analysis, it can be demonstrated that investment decisions of hospitals do not depend on isolated influencing factors but on a combination of factors. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27199146 TI - Graphitic Carbon Nitride (g-C3N4)-Based Photocatalysts for Artificial Photosynthesis and Environmental Remediation: Are We a Step Closer To Achieving Sustainability? AB - As a fascinating conjugated polymer, graphitic carbon nitride (g-C3N4) has become a new research hotspot and drawn broad interdisciplinary attention as a metal free and visible-light-responsive photocatalyst in the arena of solar energy conversion and environmental remediation. This is due to its appealing electronic band structure, high physicochemical stability, and "earth-abundant" nature. This critical review summarizes a panorama of the latest progress related to the design and construction of pristine g-C3N4 and g-C3N4-based nanocomposites, including (1) nanoarchitecture design of bare g-C3N4, such as hard and soft templating approaches, supramolecular preorganization assembly, exfoliation, and template-free synthesis routes, (2) functionalization of g-C3N4 at an atomic level (elemental doping) and molecular level (copolymerization), and (3) modification of g-C3N4 with well-matched energy levels of another semiconductor or a metal as a cocatalyst to form heterojunction nanostructures. The construction and characteristics of each classification of the heterojunction system will be critically reviewed, namely metal-g-C3N4, semiconductor-g-C3N4, isotype g-C3N4/g-C3N4, graphitic carbon-g-C3N4, conducting polymer-g-C3N4, sensitizer-g-C3N4, and multicomponent heterojunctions. The band structures, electronic properties, optical absorption, and interfacial charge transfer of g C3N4-based heterostructured nanohybrids will also be theoretically discussed based on the first-principles density functional theory (DFT) calculations to provide insightful outlooks on the charge carrier dynamics. Apart from that, the advancement of the versatile photoredox applications toward artificial photosynthesis (water splitting and photofixation of CO2), environmental decontamination, and bacteria disinfection will be presented in detail. Last but not least, this comprehensive review will conclude with a summary and some invigorating perspectives on the challenges and future directions at the forefront of this research platform. It is anticipated that this review can stimulate a new research doorway to facilitate the next generation of g-C3N4 based photocatalysts with ameliorated performances by harnessing the outstanding structural, electronic, and optical properties for the development of a sustainable future without environmental detriment. PMID- 27199147 TI - Systematically Improving Tobacco Cessation Patient Services Through Electronic Medical Record Integration. AB - The Health Information Act of 2010 has presented an opportunity to discuss, establish, and promote innovative ways to incorporate tobacco cessation assistance to patients in the health care setting. This article provides an overview of the development and implementation of an electronic tobacco cessation protocol (the eTobacco protocol), into an electronic medical record (EMR) system, while evaluating the barriers and benefits encountered. The protocol was developed to facilitate the process of electronically referring patients to a state-funded quitline service by establishing a one-click connect for providers to use within the EMR system. While evaluating the implementation of the protocol, findings indicate that several barriers were encountered including disruption of clinic workflow, EMR limitations, and training complications. In spite of the barriers, the protocol shows promising results by increasing referrals to the quitline from 7 patients the year prior to implementation to 1,254 patients after the implementation of the electronic solution. Health care systems that have the ability to modify their EMR system can help lower tobacco use rates among their patients while meeting Meaningful Use requirements. Future research should examine if referrals through the eTobacco protocol are directly associated with patients' tobacco cessation rates. PMID- 27199144 TI - Transintestinal transport of the anti-inflammatory drug 4F and the modulation of transintestinal cholesterol efflux. AB - The site and mechanism of action of the apoA-I mimetic peptide 4F are incompletely understood. Transintestinal cholesterol efflux (TICE) is a process involved in the clearance of excess cholesterol from the body. While TICE is responsible for at least 30% of the clearance of neutral sterols from the circulation into the intestinal lumen, few pharmacological agents have been identified that modulate this pathway. We show first that circulating 4F selectively targets the small intestine (SI) and that it is predominantly transported into the intestinal lumen. This transport of 4F into the SI lumen is transintestinal in nature, and it is modulated by TICE. We also show that circulating 4F increases reverse cholesterol transport from macrophages and cholesterol efflux from lipoproteins via the TICE pathway. We identify the cause of this modulation of TICE either as 4F being a cholesterol acceptor with respect to enterocytes, from which 4F enhances cholesterol efflux, or as 4F being an intestinal chaperone with respect to TICE. Our results assign a novel role for 4F as a modulator of the TICE pathway and suggest that the anti-inflammatory functions of 4F may be a partial consequence of the codependent intestinal transport of both 4F and cholesterol. PMID- 27199148 TI - A Public Policy Advocacy Project to Promote Food Security: Exploring Stakeholders' Experiences. AB - To achieve food security in Canada, comprehensive approaches are required, which involve action at the public policy level. This qualitative study explored the experiences of 14 stakeholders engaging in a 9-month participatory public policy advocacy project to promote community food security in the province of Alberta through the initiation of a campaign to develop a Universal School Food Strategy. Through this exploration, four main themes were identified; a positive and open space to contribute ideas, diversity and common ground, confidence and capacity, and uncertainty. Findings from this study suggest that the participatory advocacy project provided a positive and open space for stakeholders to contribute ideas, through which the group was able to narrow its focus and establish a goal for advocacy. The project also seems to have contributed to the group's confidence and capacity to engage in advocacy by creating a space for learning and knowledge sharing, though stakeholders expressed uncertainty regarding some aspects of the project. Findings from this study support the use of participatory approaches as a strategy for facilitating engagement in public policy advocacy and provide insight into one group's advocacy experience, which may help to inform community based researchers and advocates in the development of advocacy initiatives to promote community food security elsewhere. PMID- 27199149 TI - Impact of a Community-Based Physical Activity Program on Fitness and Adiposity Among Overweight and Obese Children. AB - This study tested whether overweight/obese children's attendance in a community based physical activity (PA) program was associated with changes in cardiorespiratory fitness (CRF) and adiposity and whether in-program activity levels influenced those associations. Program sessions (offered twice/week, 2 hours/session, over 9 months) included structured exercise/sports. At baseline and follow-up, CRF was measured as Progressive Aerobic Cardiorespiratory Endurance Run (PACER) laps, height/weight were measured, and body mass index (BMI) was calculated. Attendance was recorded as sessions attended. Children wore pedometers in 10 representative sessions; in-program activity was calculated as mean steps/minute across sessions. Linear mixed models tested associations between attendance and changes in PACER score and BMI and the influence of in program activity on those associations. A total of 101 participants (56% male, 93% Hispanic) completed baseline and one or two follow-up fitness/adiposity measurements. Attendance was associated with PACER change (beta = .093, p = .01) but not BMI change (beta = .00026, p = .97). There were significant interactions between attendance and in-program activity: Attendance more favorably affected PACER (p < .0001) and BMI (p = .03) as in-program activity levels increased. Attending community-based PA programs may improve CRF among overweight/obese children, particularly when participants are highly active during program time. Community practitioners should not only enroll overweight/obese children in PA programs but also promote adequate attendance/in-program activity levels. PMID- 27199151 TI - Exploring Instructional Strategies and Learning Theoretical Foundations of eHealth and mHealth Education Interventions. AB - This qualitative study aimed at exploring how health professionals use theories and models from the field of education to create ehealth and mhealth education interventions in an effort to provide insights for future research and practice on the development and implementation of health promotion initiatives. A purposeful sample of 12 participants was selected, using criterion and snowballing sampling strategies. Data were collected and analyzed from semistructured interviews, planning materials, and artifacts. The findings revealed that none of the participants used a specific learning theory or an instructional model in their interventions. However, based on participants' description, three themes emerged: (1) connections to behaviorist approaches to learning, (2) connections to cognitivist approaches to learning, and (3) connections to constructivist approaches to learning. Suggested implications for practice are (1) the design of a guidebook on the interplay of learning theories, instructional models, and health education and (2) the establishment of communities of practice. Further research can (1) investigate how learning theories and models intertwine with health behavior theories and models, (2) evaluate how the different instructional strategies presented in this study affect learning outcomes and health behavior change processes, and (3) investigate factors behind the instructional strategies choices made by health professionals. PMID- 27199150 TI - Motivational Interviewing in an Obesity Prevention Program for Children. AB - After-school programs are an ideal setting for childhood obesity prevention interventions. This qualitative study examined the implementation of a training technique in the Children's Healthy Eating and Exercise Program: motivational interviewing. Participants included 19 children in Grades 3 through 5, nine coaches enrolled in university health education classes, and four parents. Nine lessons were presented during the fall session (N = 5) and eight during the spring (N = 14), with five individual coaching sessions per child. From September, 2014 through April 2015, child and coach perceptions were assessed using goal sheets, surveys, a focus group, and the analysis of the video recording of a health habit commercial created by teams of children grouped by gender. Children developed weekly eating and exercise goals with coaches and reported on their progress the following week. Following the intervention, children reported improved eating and exercise habits and coaches reported they learned more about healthy food options for themselves. Overall, children responded positively to the motivational interviewing. Involving teachers may allow for dissemination of lessons and reinforcement for healthy choices during the school day. Involving parents in training may remove roadblocks to healthy lifestyle changes for children for nonschool hours and when packing lunches. PMID- 27199152 TI - Libby Wilson. PMID- 27199153 TI - Modeling Psychologists' Ethical Intention: Application of an Expanded Theory of Planned Behavior. AB - At the core of all therapeutic and medical practice lies ethics. By applying an expanded Ajzen's Theory of Planned Behavior formulation, the present investigation tested a model for explaining psychologists' intention to behave ethically. In the pretest, dual relationships and money conflicts were seen as the most prevalent dilemmas. A total of 395 clinical psychologists filled out questionnaires containing either a dual relationship dilemma describing a scenario where a psychologist was asked to treat a son of a colleague or a money focused dilemma where he or she was asked to treat a patient unable to pay for the service. Results obtained from applying the expanded Ajzen's model to each dilemma, generally, supported the study hypotheses. In particular, attitudes were seen as the most important predictor in both dilemmas followed by a morality component, defined here as the commitment of the psychologist to the patient included here as an additional predictor in the model. The expanded model provided a better understanding of ethical intention. Practical implications were also discussed. PMID- 27199154 TI - Emotional Resilience Mediates the Relationship Between Mindfulness and Emotion. AB - Previous studies have shown that mindfulness promotes positive mood states and reduces negative ones; however, the underlying mechanisms are still controversial. This study assessed the role of emotional resilience as a mediator between mindfulness and emotional regulation. A total of 421 college students (M age = 20.0 year, SD = 2.0; males/females/missing are 152/248/4) completed the Five-Facet Mindfulness Questionnaire, Profile of Mood States, and Adolescents' Emotional Resilience Questionnaire (AERQ). The ability to generate positive emotion (GP) and the ability to recover from negative emotion (RN) are two subscales of the AERQ. A Structural Equation Modeling analysis indicated that emotional resilience mediated the connection between mindfulness and emotion. Specifically, GP mediated the relationship between mindfulness and both positive and negative emotions while RN mainly mediated the relationship between mindfulness and negative emotions. These findings suggest that mindfulness may play a role in regulating positive and negative emotions through the two different aspects of emotional resilience. PMID- 27199155 TI - Nanotechnology: 21st century revolution in restorative healthcare. PMID- 27199156 TI - Nurses Teaching Prison Officers: A Workshop to Reduce the Stigmatization of Prison Inmates With Mental Illness. AB - PURPOSE: This report describes and evaluates the effectiveness of a nurse-led workshop designed to improve correctional officers' stigmatizing attitude toward inmates with mental illness. DESIGN AND METHODS: Eighty-three prison officers attended a 6-day workshop targeting the cognitive, psychoeducational, and behavioral components of publicly expressed stigma, and combining theoretical learning, observational experience on psychiatric wards, frontal lectures, case reviews, discussions, peer supervision, and simulations. The workshop's impact was measured systematically using a structured self-administered questionnaire examining cognitive, affective, and behavioral components of stigmatization. FINDINGS: The workshop significantly increased perceived knowledge and decreased stigmatizing attitudes. IMPLICATIONS FOR NURSING PRACTICE: The evaluation presented here demonstrates a less-known aspect of the possible contribution of expert psychiatric nurses to mental health education in a wider context. PMID- 27199157 TI - Lumen-apposing metal stents for drainage of pancreatic fluid collections: When and for whom? AB - BACKGROUND AND AIM: Although lumen-apposing metal stents (LAMS) are increasingly being used for drainage of pancreatic fluid collections (PFC), their advantage over plastic stents is unclear. METHODS: In this retrospective case-control study, 20 patients who underwent PFC drainage using LAMS were matched with 40 patients treated with plastic stents according to PFC type (walled-off necrosis [WON] vs pseudocyst) and procedural technique (conventional vs multi-gate). Main outcome measures were treatment success, reintervention, clinical and stent related adverse events, procedural duration, length of hospital stay (LOS) and hospital costs. RESULTS: At median follow up of 570 days, except for median procedural duration (8.5 vs 25 min, P < 0.001), there was no significant difference in treatment success (95.0 vs 92.5%, P = 0.99), reintervention (25.0 vs 30.0 %, P = 0.77), clinical (10.0 vs 12.5 %, P = 0.99) and stent-related adverse events (10.0 vs 2.5 %, P = 0.26) or median LOS (2 [IQR 1-5] vs 2 [IQR 1 7] days, P = 0.58) between patients treated with LAMS versus plastic stents. Although there was no difference for WON ($16 708 for LAMS vs $17 221 for plastic stents, P = 0.90), mean hospital costs were significantly lower for pseudocysts using plastic stents ($18 996 vs $58 649, P = 0.03). CONCLUSIONS: Although there is no difference in clinical outcomes, treating pseudocysts using plastic stents is less expensive. It is also possible that the short procedural duration is a surrogate marker for procedural complexity and this may drive the use of LAMS in sicker patients. PMID- 27199159 TI - Cytopathology of Hepatobiliary-Related Actinomycosis. AB - BACKGROUND: The clinical diagnosis of hepatobiliary-related actinomycosis can be challenging owing to its rarity and variable presentation. Moreover, actinomycotic pseudotumors may mimic malignancy and result in unnecessary surgical resection. Herein, we present the clinical and cytopathological features of 3 cases with hepatobiliary-related actinomycosis. CASES: The first patient was a 73-year-old man who presented with an exophytic liver lesion. The second patient was a 78-year-old woman who presented with a biliary stricture. The third patient was an 88-year-old woman with a right flank mass extending to the liver. The aspirate smears in these 3 cases demonstrated 'cotton ball' clusters of filamentous microorganisms and abscesses. The cell blocks of 2 of the patients showed sulfur granules with peripheral filamentous microorganisms positive with a Gram stain but negative with an acid fast stain, consistent with Actinomyces species. All patients were elderly and shared a past surgical history of laparoscopic cholecystectomy. CONCLUSION: These cases demonstrate the complementary role of cytology in the diagnosis of hepatobiliary actinomycosis. A cytologic diagnosis of actinomycosis is minimally invasive and quick. It can prompt proper culture medium selection and avoid unnecessary or extensive surgery. Based on our experience, laparoscopic cholecystectomy may be a precipitating factor for the subsequent development of hepatobiliary-related actinomycosis. PMID- 27199158 TI - Effect of two bakery products on short-term food intake and gut-hormones in young adults: a pilot study. AB - The aim of this study is to compare the effect of conventional bread and a whole grain bread on appetite and energy intake, satiety and satiety gut-hormones. A randomized controlled crossover pilot study was carried out in 11 university students (age: 18.7 +/- 0.9 years; body mass index: 22.7 +/- 2.7 kg/m(2)). Participants consumed two different mid-morning cereal-based snacks, including a conventional or whole grain bread. Two testing days were completed, including satiety questionnaires, blood sampling and consumption of standardized breakfast, mid-morning test-snacks and ad libitum lunch. Several gut-hormones were analysed and satiation was assessed using Visual Analogue Scale scores. The consumption of whole grain bread increased satiety perception, decreased the remained energy intake during the testing day, and decreased the postprandial response of peptide YY, compared with conventional bread (p < 0.005). These data suggest that the consumption of whole grain bread might be a useful strategy to improve satiety. PMID- 27199160 TI - Hierarchically Mesoporous o-Hydroxyazobenzene Polymers: Synthesis and Their Applications in CO2 Capture and Conversion. AB - The synthesis of hierarchically mesoporous polymers with multiple functionalities is challenging. Herein we reported a template-free strategy for synthesis of phenolic azo-polymers with hierarchical porous structures based on diazo-coupling reaction in aqueous solution under mild conditions. The resultant polymers have surface areas up to 593 m(2) g(-1) with the mesopore ratio of >80 %, and a good ability to complex with metal ions, such as Cu(2+) , Zn(2+) ,Ni(2+) , achieving a metal loading up to 26.24 wt %. Moreover, the polymers complexed with Zn showed excellent performance for catalyzing the reaction of CO2 with epoxide, affording a TOF of 2570 h(-1) in the presence of tetrabutyl ammonium bromide (7.2 mol %). The polymer complexed with Cu could catalyze the oxidation of alcohol with high efficiency. PMID- 27199161 TI - The Effect of Specimen Preparation on Post-Excision and Post-Fixation Dimensions, Translation, and Distortion of Canine Cadaver Skin-Muscle-Fascia Specimens. AB - OBJECTIVE: To assess the effect of various tissue apposition techniques on specimens after formalin fixation, and to assess canine cadaveric composite skin muscle-fascia specimen changes after excision without and with addition of a tumor model. STUDY DESIGN: Canine cadaveric study; unbalanced paired design. ANIMALS: Fresh canine cadavers (n = 30) METHODS: Experiment 1: Paired 7 cm diameter, circular skin-muscle-fascia specimens were harvested bilaterally from three sites (thorax, abdomen, and thigh) on 10 cadavers. For each pair, the skin to-fascia was sutured with a circumferential continuous pattern in one specimen and left unsutured in the other during excision. Specimen length and width were measured post-excision and post-fixation. Specimen rotation, translation, and distortion was measured post-fixation. Experiment 2: A subcutaneous tumor model was implanted at 2 sites (neck, thorax) on 20 cadavers and specimens were then excised with 2 cm lateral margins and a deep fascial plane. Three suturing techniques of the skin-to-fascia at both sites were performed during excision: unsutured versus circumferential continuous suture (10 pairs) or circumferential versus 4 interrupted quadrant sutures (10 pairs). Lateral margins were compared post-excision and post-fixation. RESULTS: Experiment 1: There was significant reduction in the length and width of the fascia and skin post-excision, but no further reduction after fixation. The circumferential suture decreased rotation and translation of the tissue layers but did not significantly affect specimen shrinkage or distortion compared with the unsutured specimen. Experiment 2: All 4 lateral margins decreased significantly post-excision and post-fixation compared with the planned pre-excision margins. No difference was found between any of the 4 lateral margins for any skin-to-fascia suture technique. CONCLUSION: Canine skin-muscle-fascia specimens significantly decrease in size from gross pre excision dimensions after removal. Suturing the specimen during surgery before excision will significantly improve alignment of tissue planes without creating distortion of the sample, but may alter the length, width, and lateral margins of the specimen. PMID- 27199163 TI - High-resolution Imaging of pH in Alkaline Sediments and Water Based on a New Rapid Response Fluorescent Planar Optode. AB - A new dual-lumophore optical sensor combined with a robust RGB referencing method was developed for two-dimensional (2D) pH imaging in alkaline sediments and water. The pH sensor film consisted of a proton-permeable polymer (PVC) in which two dyes with different pH sensitivities and emission colors: (1) chloro phenyl imino propenyl aniline (CPIPA) and (2) the coumarin dye Macrolex((r)) fluorescence yellow 10 GN (MFY-10 GN) were entrapped. Calibration experiments revealed the typical sigmoid function and temperature dependencies. This sensor featured high sensitivity and fast response over the alkaline working ranges from pH 7.5 to pH 10.5. Cross-sensitivity towards ionic strength (IS) was found to be negligible for freshwater when IS <0.1 M. The sensor had a spatial resolution of approximately 22 MUm and aresponse time of <120 s when going from pH 7.0 to 9.0. The feasibility of the sensor was demonstrated using the pH microelectrode. An example of pH image obtained in the natrual freshwater sediment and water associated with the photosynthesis of Vallisneria spiral species was also presented, suggesting that the sensor held great promise for the field applications. PMID- 27199164 TI - The Effects of Tumstatin on Vascularity, Airway Inflammation and Lung Function in an Experimental Sheep Model of Chronic Asthma. AB - Tumstatin, a protein fragment of the alpha-3 chain of Collagen IV, is known to be significantly reduced in the airways of asthmatics. Further, there is evidence that suggests a link between the relatively low level of tumstatin and the induction of angiogenesis and inflammation in allergic airway disease. Here, we show that the intra-segmental administration of tumstatin can impede the development of vascular remodelling and allergic inflammatory responses that are induced in a segmental challenge model of experimental asthma in sheep. In particular, the administration of tumstatin to lung segments chronically exposed to house dust mite (HDM) resulted in a significant reduction of airway small blood vessels in the diameter range 10(+)-20 MUm compared to controls. In tumstatin treated lung segments after HDM challenge, the number of eosinophils was significantly reduced in parenchymal and airway wall tissues, as well as in the bronchoalveolar lavage fluid. The expression of VEGF in airway smooth muscle was also significantly reduced in tumstatin-treated segments compared to control saline-treated segments. Allergic lung function responses were not attenuated by tumstatin administration in this model. The data are consistent with the concept that tumstatin can act to suppress vascular remodelling and inflammation in allergic airway disease. PMID- 27199162 TI - Microglia-derived purines modulate mossy fibre synaptic transmission and plasticity through P2X4 and A1 receptors. AB - Recent data have provided evidence that microglia, the brain-resident macrophage like cells, modulate neuronal activity in both physiological and pathophysiological conditions, and microglia are therefore now recognized as synaptic partners. Among different neuromodulators, purines, which are produced and released by microglia, have emerged as promising candidates to mediate interactions between microglia and synapses. The cellular effects of purines are mediated through a large family of receptors for adenosine and for ATP (P2 receptors). These receptors are present at brain synapses, but it is unknown whether they can respond to microglia-derived purines to modulate synaptic transmission and plasticity. Here, we used a simple model of adding immune challenged microglia to mouse hippocampal slices to investigate their impact on synaptic transmission and plasticity at hippocampal mossy fibre (MF) synapses onto CA3 pyramidal neurons. MF-CA3 synapses show prominent forms of presynaptic plasticity that are involved in the encoding and retrieval of memory. We demonstrate that microglia-derived ATP differentially modulates synaptic transmission and short-term plasticity at MF-CA3 synapses by acting, respectively, on presynaptic P2X4 receptors and on adenosine A1 receptors after conversion of extracellular ATP to adenosine. We also report that P2X4 receptors are densely located in the mossy fibre tract in the dentate gyrus-CA3 circuitry. In conclusion, this study reveals an interplay between microglia-derived purines and MF-CA3 synapses, and highlights microglia as potent modulators of presynaptic plasticity. PMID- 27199165 TI - Multifunctional hydrogel nano-probes for atomic force microscopy. AB - Since the invention of the atomic force microscope (AFM) three decades ago, there have been numerous advances in its measurement capabilities. Curiously, throughout these developments, the fundamental nature of the force-sensing probe the key actuating element-has remained largely unchanged. It is produced by long established microfabrication etching strategies and typically composed of silicon based materials. Here, we report a new class of photopolymerizable hydrogel nano probes that are produced by bottom-up fabrication with compressible replica moulding. The hydrogel probes demonstrate excellent capabilities for AFM imaging and force measurement applications while enabling programmable, multifunctional capabilities based on compositionally adjustable mechanical properties and facile encapsulation of various nanomaterials. Taken together, the simple, fast and affordable manufacturing route and multifunctional capabilities of hydrogel AFM nano-probes highlight the potential of soft matter mechanical transducers in nanotechnology applications. The fabrication scheme can also be readily utilized to prepare hydrogel cantilevers, including in parallel arrays, for nanomechanical sensor devices. PMID- 27199167 TI - Child diarrhoea and nutritional status in rural Rwanda: a cross-sectional study to explore contributing environmental and demographic factors. AB - OBJECTIVE: To explore associations of environmental and demographic factors with diarrhoea and nutritional status among children in Rusizi district, Rwanda. METHODS: We obtained cross-sectional data from 8847 households in May-August 2013 from a baseline survey conducted for an evaluation of an integrated health intervention. We collected data on diarrhoea, water quality, and environmental and demographic factors from households with children <5, and anthropometry from children <2. We conducted log-binomial regression using diarrhoea, stunting and wasting as dependent variables. RESULTS: Among children <5, 8.7% reported diarrhoea in the previous 7 days. Among children <2, stunting prevalence was 34.9% and wasting prevalence was 2.1%. Drinking water treatment (any method) was inversely associated with caregiver-reported diarrhoea in the previous 7 days (PR = 0.79, 95% CI: 0.68-0.91). Improved source of drinking water (PR = 0.80, 95% CI: 0.73-0.87), appropriate treatment of drinking water (PR = 0.88, 95% CI: 0.80 0.96), improved sanitation facility (PR = 0.90, 95% CI: 0.82-0.97), and complete structure (having walls, floor and roof) of the sanitation facility (PR = 0.65, 95% CI: 0.50-0.84) were inversely associated with stunting. None of the exposure variables were associated with wasting. A microbiological indicator of water quality was not associated with diarrhoea or stunting. CONCLUSIONS: Our findings suggest that in Rusizi district, appropriate treatment of drinking water may be an important factor in diarrhoea in children <5, while improved source and appropriate treatment of drinking water as well as improved type and structure of sanitation facility may be important for linear growth in children <2. We did not detect an association with water quality. PMID- 27199168 TI - Molecular dynamics of anhydrous glycolipid self-assembly in lamellar and hexagonal phases. AB - The molecular dynamics of a synthetic branched chain glycolipid, 2-decyl tetradecyl-beta-d-maltoside (C14-10G2), in the dry assemblage of smectic and columnar liquid crystal phases has been studied by dielectric spectroscopy as a function of frequency and temperature during the cooling process. Strong relaxation modes were observed corresponding to the tilted smectic and columnar phases, respectively. At low frequency (~900 Hz to 1 kHz) in the smectic phase, Process I* was observed due to the tilted sugar bilayer structure. The process continued in the columnar phase (Process I) with an abrupt dynamic change due to phase transition in the frequency range of ~1.3 kHz to 22 kHz. An additional process (Process II) was observed in the columnar phase with a broader relaxation in the frequency range of ~10 Hz to 1 kHz. A bias field dependence study was performed in the columnar phase and we found that the relaxation strength rapidly decreased with increased applied dc bias field. This relaxation originates from a collective motion of polar groups within the columns. The results of dielectric spectroscopy were supported by a molecular dynamics simulation study to identify the origin of the relaxation processes, which could be related to the chirality and hydrogen bonds of the sugar lipid. PMID- 27199169 TI - Legionnaires' disease caused by Legionella longbeachae: Clinical features and outcomes of 107 cases from an endemic area. AB - BACKGROUND AND OBJECTIVE: Legionella longbeachae is a predominant cause of Legionnaires' disease in some parts of the world, particularly in Australasia. Clinical reports of L. longbeachae infection are limited to case reports or small case series, and culture-confirmed cases. METHODS: We reviewed the clinical characteristics and outcomes of L. longbeachae pneumonia in a large case series from Christchurch, New Zealand during a 4-year period when both PCR and cultures were used as routine diagnostic tools for Legionnaires' disease. Cases of Legionella pneumophila pneumonia were reviewed for comparison. RESULTS: A total of 107 cases of L. longbeachae infection were identified by PCR and/or culture. The median age was 65 years (range 25-90 years), 63% were male, and most became unwell during spring or summer. Presenting clinical features were similar to those reported for community-acquired pneumonia, with headache, myalgia and diarrhoea being common. Elevated C-reactive protein, hyponatraemia and abnormal liver function tests were also common. History of productive cough, involvement of both lungs, and high bacterial load were independently associated with culture of Legionella from lower respiratory samples. One quarter required intensive care unit admission, and 5% died. Among patients given antimicrobial therapy before admission, those given agents without anti-Legionella activity were more likely to be admitted to the intensive care unit. Limited comparisons were made with the 19 L. pneumophila cases over the same time period. CONCLUSION: Characteristics of L. longbeachae pneumonia are broadly similar to those reported for community acquired pneumonia from a variety of other populations, except for the spring/summer seasonality. PMID- 27199166 TI - Skeletal muscle fiber type: using insights from muscle developmental biology to dissect targets for susceptibility and resistance to muscle disease. AB - Skeletal muscle fibers are classified into fiber types, in particular, slow twitch versus fast twitch. Muscle fiber types are generally defined by the particular myosin heavy chain isoforms that they express, but many other components contribute to a fiber's physiological characteristics. Skeletal muscle fiber type can have a profound impact on muscle diseases, including certain muscular dystrophies and sarcopenia, the aging-induced loss of muscle mass and strength. These findings suggest that some muscle diseases may be treated by shifting fiber type characteristics either from slow to fast, or fast to slow phenotypes, depending on the disease. Recent studies have begun to address which components of muscle fiber types mediate their susceptibility or resistance to muscle disease. However, for many diseases it remains largely unclear why certain fiber types are affected. A substantial body of work has revealed molecular pathways that regulate muscle fiber type plasticity and early developmental muscle fiber identity. For instance, recent studies have revealed many factors that regulate muscle fiber type through modulating the activity of the muscle regulatory transcription factor MYOD1. Future studies of muscle fiber type development in animal models will continue to enhance our understanding of factors and pathways that may provide therapeutic targets to treat muscle diseases. WIREs Dev Biol 2016, 5:518-534. doi: 10.1002/wdev.230 For further resources related to this article, please visit the WIREs website. PMID- 27199170 TI - Planning to make economic decisions in the future, but choosing impulsively now: are preference reversals related to symptoms of ADHD and depression? AB - A preference for smaller immediate rewards over larger delayed rewards (delay discounting, DD) is common in attention deficit hyperactivity disorder (ADHD), but rarely investigated in depression. Whether this preference is due to sensitivity to reward immediacy or delay aversion remains unclear. To investigate this, we examined whether ADHD and depressive symptoms are associated with preference reversals: a switch from smaller immediate rewards to larger delayed rewards when smaller rewards are also delayed. We also examined whether these symptoms differentially affect DD of losses. In Study 1 undergraduates completed a questionnaire about ADHD symptoms, and performed a hypothetical DD task. In the NOW condition, participants were presented with choices between a small reward available today and a large reward available after one year. In the FUTURE condition both rewards were delayed with +1 year. In Study 2 undergraduates completed questionnaires about ADHD and depressive symptoms and performed a DD task with gains and losses. Participants showed preference reversals in both studies and tasks. Losses were less steeply discounted than gains. ADHD and depressive symptoms did not influence these effects. Depressive symptoms, but not ADHD symptoms, were associated with less economic choices in general. These findings suggest that impulsive choice in depression is not explained by sensitivity to reward immediacy. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27199171 TI - "It's like a puzzle": Pregnant women's perceptions of professional support in midwifery care. AB - PROBLEM: Pregnant women are not always satisfied with the professional support they receive during their midwifery care. More knowledge is needed to understand what professional support pregnant women need for childbirth and parenting. BACKGROUND: Childbearing and the transition to becoming a parent is a sensitive period in one's life during which one should have the opportunity to receive professional support. Professional support does not always correspond to pregnant women's needs. To understand pregnant women's needs for professional support within midwifery care, it is crucial to further illuminate women's experiences of this support. AIM: To explore pregnant women's perceptions of professional support in midwifery care. METHODS: A qualitative study using semi-structured interviews. Fifteen women were interviewed during gestational weeks 36-38. Data was analysed using phenomenography. FINDINGS: The women perceived professional support in midwifery care to be reassuring and emotional, to consist of reliable information, and to be mediated with pedagogical creativity. The professional support facilitated new social contacts, partner involvement and contributed to mental preparedness. The findings of the study were presented in six categories and the category Professional support contributes to mental preparedness was influenced by the five other categories. CONCLUSION: Pregnant women prepare for childbirth and parenting by using several different types of professional support in midwifery care: a strategy that could be described as piecing together a puzzle. When the women put the puzzle together, each type of professional support works as a valuable piece in the whole puzzle. Through this, professional support could contribute to women's mental preparedness for childbirth and parenting. PMID- 27199172 TI - An overview of the first 'no exit' midwifery group practice in a tertiary maternity hospital in Western Australia: Outcomes, satisfaction and perceptions of care. AB - BACKGROUND: Midwifery group practice (MGP) is a care model offered by a primary midwife in a small team. Evidence confirms MGP is acceptable to women, safe and cost effective. METHODS: We aimed to provide a systematic overview of the first 'no exit' MGP in a Western Australian (WA) tertiary maternity hospital, using a mixed methods approach, involving four phases. Between July 2013 and June 2014: phase one assessed MGP characteristics, obstetric and neonatal outcomes by parity; phase two examined women's satisfaction by mode of delivery; and phase three qualitatively explored perceptions of care. Phase four compared the proportion of MGP women and the 2012 WA birthing population. FINDINGS: Phase one included 232 MGP women; 87% achieved a vaginal birth. Phase two included 97% (226 of 232) women, finding 98% would recommend the service. Phase three analysis of 62 interviews revealed an overarching theme 'Continuity with Midwives' encompassing six sub-themes: only a phone call away; home away from home; knowing me; a shared view; there for me; and letting it happen. Phase four compared the MGP cohort to 33,393 WA women. Intrapartum MGP women were more likely than the WA population to have a vaginal birth (87% vs 65%, P<=0.001) and intact perineum (49% vs 36%, P<=0.001) and less likely to use epidural/spinal analgesia (34% vs 59%, P<=0.001), or have a caesarean (13% vs 35%, P<=0.001). CONCLUSIONS: Mixed methods enabled systematic examination of this new 'no exit' MGP confirming safety and acceptability. Findings contribute to our knowledge of MGP models. PMID- 27199174 TI - Mandibular reconstruction with costochondral grafts in children: a case report. PMID- 27199173 TI - A Small Molecule Inhibitor of PDK1/PLCgamma1 Interaction Blocks Breast and Melanoma Cancer Cell Invasion. AB - Strong evidence suggests that phospholipase Cgamma1 (PLCgamma1) is a suitable target to counteract tumourigenesis and metastasis dissemination. We recently identified a novel signalling pathway required for PLCgamma1 activation which involves formation of a protein complex with 3-phosphoinositide-dependent protein kinase 1 (PDK1). In an effort to define novel strategies to inhibit PLCgamma1 dependent signals we tested here whether a newly identified and highly specific PDK1 inhibitor, 2-O-benzyl-myo-inositol 1,3,4,5,6-pentakisphosphate (2-O-Bn InsP5), could affect PDK1/PLCgamma1 interaction and impair PLCgamma1-dependent cellular functions in cancer cells. Here, we demonstrate that 2-O-Bn-InsP5 interacts specifically with the pleckstrin homology domain of PDK1 and impairs formation of a PDK1/PLCgamma1 complex. 2-O-Bn-InsP5 is able to inhibit the epidermal growth factor-induced PLCgamma1 phosphorylation and activity, ultimately resulting in impaired cancer cell migration and invasion. Importantly, we report that 2-O-Bn-InsP5 inhibits cancer cell dissemination in zebrafish xenotransplants. This work demonstrates that the PDK1/PLCgamma1 complex is a potential therapeutic target to prevent metastasis and it identifies 2-O-Bn-InsP5 as a leading compound for development of anti-metastatic drugs. PMID- 27199175 TI - Accurate genial tubercle capturing method using computer-assisted virtual surgery for genioglossus advancement. PMID- 27199176 TI - Genetics: Defining driver mutations in the genomic landscape of breast cancer. PMID- 27199177 TI - Gynaecological cancer: Chemoresistance - a little help from friends. PMID- 27199178 TI - Health policy: Overcoming cost barriers to clinical trial participation. PMID- 27199179 TI - The Intersession Process in Psychotherapy for Anorexia Nervosa: Characteristics and Relation to Outcome. AB - OBJECTIVE: The "inter session process" (ISP) is defined as therapy-related conscious thoughts, memories, and emotions that patients and therapists experience between psychotherapy sessions. It indicates how the participants process and use treatment. The main aim of this study is to describe the ISP characteristics of patients in outpatient treatment for anorexia nervosa (AN). An additional aim is to explore the relation between patients' ISP and treatment outcome. METHOD: Patients taking part in a randomized controlled trial on outpatient psychotherapy for AN (ANTOP) filled in the Intersession Experience Questionnaire before each of the 40 psychotherapy sessions. Trajectories of different aspects of the ISP were analyzed with growth curve models based on orthogonal polynomials and tested for differences between 3 outcome categories (recovery, partially recovered, full syndrome AN). RESULTS: Data from 108 cases were available for analysis. ISP facets showed diverse, mostly nonlinear, trajectories over the course of treatment. Less favorable outcomes were associated with higher levels of patients' experiencing negative emotions when recalling therapeutic dialogue, thinking about therapy during dreaming/drowsy states, and applying therapeutic learning (in the second half of treatment). CONCLUSIONS: Findings confirm an overall relation between ISP and treatment outcome. In outpatient treatment in AN, patients with a less successful course seem to be more preoccupied with therapy and therapist between sessions. For the ISP facet "applying therapeutic learning," findings point to an optimal range dependent on treatment phase. Growth curve modeling is required to describe the nonlinear trajectories of ISP facets. PMID- 27199180 TI - Can data in optometric practice be used to provide an evidence base for ophthalmic public health? AB - PURPOSE: The purpose of this paper is to investigate the potential of using primary care optometry data to support ophthalmic public health, research and policy making. METHODS: Suppliers of optometric electronic patient record systems (EPRs) were interviewed to gather information about the data present in commercial software programmes and the feasibility of data extraction. Researchers were presented with a list of metrics that might be included in an optometric practice dataset via a survey circulated by email to 102 researchers known to have an interest in eye health. Respondents rated the importance of each metric for research. A further survey presented the list of metrics to 2000 randomly selected members of the College of Optometrists. The optometrists were asked to specify how likely they were to enter information about each metric in a routine sight test consultation. They were also asked if data were entered as free text, menus or a combination of these. RESULTS: Current EPRs allowed the input of data relating to the metrics of interest. Most data entry was free text. There was a good match between high priority metrics for research and those commonly recorded in optometric practice. CONCLUSIONS: Although there were plenty of electronic data in optometric practice, this was highly variable and often not in an easily analysed format. To facilitate analysis of the evidence for public health purposes a UK based minimum dataset containing standardised clinical information is recommended. Further research would be required to develop suitable coding for the individual metrics included. The dataset would need to capture information from all sectors of the population to ensure effective planning of any future interventions. PMID- 27199181 TI - The role of vagal pathway and NK1 and NK2 receptors in cardiovascular and respiratory effects of neurokinin A. AB - Neurokinin A (NKA) is a peptide neurotransmitter that participates in the regulation of breathing and the cardiovascular system. The purpose of the current study was to determine the cardiorespiratory pattern exerted by the systemic injection of NKA, to look at the contribution of neurokinin NK1 and NK2 receptors, and to establish the engagement of the vagal pathway in mediation of these responses. The effects of intravenous injections of NKA (50 MUg/kg) were studied in anaesthetized, spontaneously breathing rats in the following experimental schemes: in neurally intact rats; and vagotomized at either midcervical or supranodosal level. Intravenous injections of NKA in the intact rats evoked sudden and short-lived increase in the respiratory rate concomitant with drop in tidal volume, followed by a prolonged depression, coupled with continuous augmentation of the tidal volume. Respiratory alterations were accompanied by transient tachycardia and prolonged hypotension. Midcervical vagotomy eliminated respiratory rate response and augmentation of tidal volume. Section of supranodosal vagi abrogated all respiratory reactions. NK2 receptor blockade abolished respiratory changes without affecting cardiovascular effects, whereas NK1 receptor blockade significantly reduced hypotension and increase in heart rate with no impact on the respiratory system. These results indicate that NKA induced changes in the breathing resulting from an excitation of the NK2 receptors on the vagal endings. A fall in blood pressure triggered by NKA occurs outside of the vagus nerve and is probably mediated via its direct action on vascular smooth muscles supplied with NK1 receptors. PMID- 27199183 TI - Erratum: Predictive analytics of environmental adaptability in multi-omic network models. PMID- 27199184 TI - Charge transport-driven selective oxidation of graphene. AB - Due to the tunability of the physical, electrical, and optical characteristics of graphene, precisely controlling graphene oxidation is of great importance for potential applications of graphene-based electronics. Here, we demonstrate a facile and precise way for graphene oxidation controlled by photoexcited charge transfer depending on the substrate and bias voltage. It is observed that graphene on TiO2 is easily oxidized under UV-ozone treatment, while graphene on SiO2 remains unchanged. The mechanism for the selective oxidation of graphene on TiO2 is associated with charge transfer from the TiO2 to the graphene. Raman spectra were used to investigate the graphene following applied bias voltages on the graphene/TiO2 diode under UV-ozone exposure. We found that under a reverse bias of 0.6 V on the graphene/TiO2 diode, graphene oxidation was accelerated under UV-ozone exposure, thus confirming the role of charge transfer between the graphene and the TiO2 that results in the selective oxidation of the graphene. The selective oxidation of graphene can be utilized for the precise, nanoscale patterning of the graphene oxide and locally patterned chemical doping, finally leading to the feasibility and expansion of a variety of graphene-based applications. PMID- 27199185 TI - Electronic state-lifetime interference in resonant Auger spectra: a tool to disentangle overlapping core-excited states. AB - We have measured resonant-Auger decay following Cl 1s(-1) excitations in HCl and CH3Cl molecules, and extracted the pseudo-cross sections of different Cl 2p(-2) final states. These cross sections show clear evidence of shake processes as well as contributions of electronic state-lifetime interference (ELI). To describe the spectra we developed a fit approach that takes into account ELI contributions and ultrafast nuclear dynamics in dissociative core-excited states. Using this approach we utilized the ELI contributions to obtain the intensity ratios of the overlapping states Cl 1s(-1)4ppi/1s(-1)4psigma in HCl and Cl 1s(-1)4pe/1s(-1)4pa1 in CH3Cl. The experimental value for HCl is compared with theoretical results showing satisfactory agreement. PMID- 27199182 TI - The molecular spectrum and distribution of haemoglobinopathies in Cyprus: a 20 year retrospective study. AB - Haemoglobinopathies are the most common monogenic diseases, posing a major public health challenge worldwide. Cyprus has one the highest prevalences of thalassaemia in the world and has been the first country to introduce a successful population-wide prevention programme, based on premarital screening. In this study, we report the most significant and comprehensive update on the status of haemoglobinopathies in Cyprus for at least two decades. First, we identified and analysed all known 592 beta-thalassaemia patients and 595 Hb H disease patients in Cyprus. Moreover, we report the molecular spectrum of alpha-, beta- and delta-globin gene mutations in the population and their geographic distribution, using a set of 13824 carriers genotyped from 1995 to 2015, and estimate relative allele frequencies in carriers of beta- and delta-globin gene mutations. Notably, several mutations are reported for the first time in the Cypriot population, whereas important differences are observed in the distribution of mutations across different districts of the island. PMID- 27199186 TI - Risk perception in pregnancy: a concept analysis. AB - AIM: To report an analysis of the concept of risk perception in pregnancy. BACKGROUND: Pregnant women are increasingly exposed to the view that pregnancy and childbirth are intrinsically dangerous, requiring medical monitoring and management. Societal pressures are applied to women that dictate appropriate behaviours during pregnancy. These changes have resulted in increased perception of risk for pregnant women. DESIGN: Walker and Avant's method was selected to guide this analysis. DATA SOURCES: Peer-reviewed articles published in English from CINAHL, Scopus, PubMed and Psychinfo. No date limits were applied. METHODS: Thematic analysis was conducted on 79 articles. Attributes, antecedents and consequences of the concept were identified. RESULTS: The attributes of the concept are the possibility of harm to mother or infant and beliefs about the severity of the risk state. The physical condition of pregnancy combined with the cognitive ability to perceive a personal risk state is antecedents. Risk perception in pregnancy influences women's affective state and has an impact on decision-making about pregnancy and childbirth. There are limited empirical referents with which to measure the concept. CONCLUSION: Women today know more about their developing infant than at any other time in history; however, this has not led to a sense of reassurance. Nurses and midwives have a critical role in assisting pregnant women, and their families make sense of the information they are exposed to. An understanding of the complexities of the concept of risk perception in pregnancy may assist in enabling nurses and midwives to reaffirm the normalcy of pregnancy. PMID- 27199187 TI - Endothelium-dependent hyperpolarizations in health and disease. PMID- 27199188 TI - Congratulations on the 25th Anniversary of the IMIA Yearbook! PMID- 27199190 TI - Towards Clinical Bioinformatics: Redux 2015. AB - In 2004, medical informatics as a scientific community recognized an emerging field of "clinical bioinformatics" that included work bringing bioinformatics data and knowledge into the clinic. In the intervening decade, "translational biomedical informatics" has emerged as the umbrella term for the work that brings together biological entities and clinical entities. The major challenges continue: understanding the clinical significance of basic 'omics' (and other) measurements, and communicating this to increasingly empowered patients/consumers who often have access to this information outside usual medical channels. It has become clear that basic molecular information must be combined with environmental and lifestyle data to fully define, predict, and manage health status.. PMID- 27199189 TI - Silver Anniversary: 25 Editions of the IMIA Yearbook. AB - OBJECTIVES: To provide an editorial introduction into the special 25th anniversary edition of the IMIA Yearbook of Medical Informatics with discussion of the significance of the Yearbook, past and current editorial teams, and a look into the future. METHODS: A brief overview of the 2016 anniversary edition of the Yearbook allows for a discussion of the significance and value of the Yearbook to the Biomedical Informatics community as well as a review of changes in Yearbook team and format over time. RESULTS: The IMIA Yearbook celebrates its 25th edition bearing witness to the quality of the IMIA brand, the Yearbook content, as well as to the dedication of and the inordinate amount of labor from the authors and editors of the Yearbook. Editorial teams are to be applauded for their hard work and for their foresight in steering the Yearbook from a paperback to an open access online publication. The special edition provides reviews of past editorials with the knowledge of today. CONCLUSIONS: The IMIA Yearbook celebrates a remarkable milestone providing a testament to the maturity of the Biomedical Informatics field. Informaticians across the world are encouraged to thank past editorial teams and celebrate with IMIA. PMID- 27199191 TI - Medical Imaging Informatics: Towards a Personalized Computational Patient. AB - Medical Imaging Informatics has become a fast evolving discipline at the crossing of Informatics, Computational Sciences, and Medicine that is profoundly changing medical practices, for the patients' benefit. PMID- 27199192 TI - Reflections on the Yearbook from the 1990's to the Present. AB - The authors highlight IMIA's progress over the past twenty years as a key bridging organization that translates health informatics theory into practice. In contrast, they describe that electronic health record (EHR) systems built in the 20th Century are not meeting the needs of clinical users. Moreover, these EHRs are not architected to keep pace with the rapid changes in the evolving health ecosystem. They conclude that 21st Century health IT systems need to be architected into an ecosystem-wide suite of interacting complex adaptive systems that support individuals, clinicians, managers and policy-makers with the high value/high usability computing paradigm that dominates the Internet today. PMID- 27199193 TI - Preface - Access to Knowledge Revisited. AB - OBJECTIVE: To review and update the Preface to the 1998 Yearbook of Medical Informatics, which had as its Special Topic "Health Informatics and the Internet". METHOD: Assessment of the accuracy of predictions made in 1998 and consideration of key developments in informatics since that time. RESULTS: Predictions made in 1998 were generally accurate regarding reduced dependence on keyboards, expansion of multimedia, medical data privacy policy development, impact of molecular biology on knowledge and treatment of neoplasms, and use of imaging and informatics to advance understanding of brain structure and function. Key developments since 1998 include the huge increase in publicly available electronic information; acknowledgement by leaders in government and science of the importance of biomedical informatics to societal goals for health, health care, and scientific discovery; the influence of the public in promoting clinical research transparency and free access to government-funded research results; the long-awaited arrival of electronic health records; and the "Cloud" as a 21st century reformulation of contracting out the computer center. CONCLUSIONS: There are many challenging and important problems that deserve the attention of the informatics community. Informatics researchers will be best served by embracing a very broad definition of medical informatics and by promoting public understanding of the field. PMID- 27199194 TI - Integration of Information for Patient Care: 2015 Redux. AB - Medical workstations are getting more and more powerful - however for the last decades they have been slow in making their way into the everyday life in medical care. In some resource rich organisations or smaller countries, their advance has gone further than elsewhere - however, a tipping point has not been reached. Again and again, new technologies and developments are pushing the need for integration of workstations into medical processes - currently the quantified self wave - however more options lead to more complexity and this growing complexity makes it more difficult to integrate the power of medical workstations in given culturally primed scenarios. PMID- 27199195 TI - The Renewed Promise of Medical Informatics. AB - The promise of the field of Medical Informatics has been great and its impact has been significant. In 1999, the Yearbook editors of the International Medical Informatics Association (IMIA) - also the authors of the present paper - sought to assess this impact by selecting a number of seminal papers in the field, and asking experts to comment on these articles. In particular, it was requested whether and how the expectations, represented by these papers, had been fulfilled since their publication several decades earlier. Each expert was also invited to comment on what might be expected in the future. In the present paper, these areas are briefly reviewed again. Where did these early papers have an impact and where were they not as successful as originally expected? It should be noted that the extraordinary developments in computer technology observed in the last two decades could not have been foreseen by these early researchers. In closing, some of the possibilities and limitations of research in medical informatics are outlined in the context of a framework that considers six levels of computer applications in medicine and health care. For each level, some predictions are made for the future, concluded with thoughts on fruitful areas for ongoing research in the field. PMID- 27199196 TI - Consumer Health Informatics: Past, Present, and Future of a Rapidly Evolving Domain. AB - OBJECTIVES: Consumer Health Informatics (CHI) is a rapidly growing domain within the field of biomedical and health informatics. The objective of this paper is to reflect on the past twenty five years and showcase informatics concepts and applications that led to new models of care and patient empowerment, and to predict future trends and challenges for the next 25 years. METHODS: We discuss concepts and systems based on a review and analysis of published literature in the consumer health informatics domain in the last 25 years. RESULTS: The field was introduced with the vision that one day patients will be in charge of their own health care using informatics tools and systems. Scientific literature in the field originally focused on ways to assess the quality and validity of available printed health information, only to grow significantly to cover diverse areas such as online communities, social media, and shared decision-making. Concepts such as home telehealth, mHealth, and the quantified-self movement, tools to address transparency of health care organizations, and personal health records and portals provided significant milestones in the field. CONCLUSION: Consumers are able to actively participate in the decision-making process and to engage in health care processes and decisions. However, challenges such as health literacy and the digital divide have hindered us from maximizing the potential of CHI tools with a significant portion of underserved populations unable to access and utilize them. At the same time, at a global scale consumer tools can increase access to care for underserved populations in developing countries. The field continues to grow and emerging movements such as precision medicine and the sharing economy will introduce new opportunities and challenges. PMID- 27199199 TI - Platelets and Inflammatory Parameters Do Not Affect Long-Term Survival after Acute Stroke. AB - RATIONALE: According to literature, the inflammatory response and platelets are associated with coronary heart disease mortality. In this study, we examine if similar relationships exist after acute cerebral infarctions. DESIGN: Between 2005 and 2007, individuals (n = 61) hospitalized with acute stroke were investigated 2.1 +/- .3 (SD) days after hospital admission. After 9.3 +/- .7 (SD) years, 29 patients (age 79 +/- 8 [SD]; 12 women) had died. They were compared with survivors (age 69 +/- 9 [SD]; 9 women) with respect to inflammatory parameters and platelet features such as activity and reactivity. RESULTS AND CONCLUSION: Inflammation and platelets at the acute event do not forecast long term survival of stroke sufferers. PMID- 27199198 TI - Population-Attributable Risk of Risk Factors for Recurrent Wheezing in Moderate Preterm Infants During the First Year of Life. AB - BACKGROUND: Recurrent wheezing in young infants has a high prevalence, influences quality of life, and generates substantial health care costs. We previously showed that respiratory syncytial virus infection is an important mechanism of recurrent wheezing in moderate preterm infants. We aimed to provide population attributable risks (PAR) of risk factors for recurrent wheezing during the first year of life in otherwise healthy moderate preterm infants. METHODS: RISK is a multicentre prospective birth cohort study of 4424 moderate preterm infants born at 32-35 weeks gestation. We estimated PAR of risk factors for recurrent wheezing, which was defined as three or more parent-reported wheezing episodes during the first year of life. RESULTS: We evaluated 3952 (89%) children at 1 year of age, of whom 705 infants (18%) developed recurrent wheezing. Fourteen variables were independently associated with recurrent wheezing. Hospitalisation for respiratory syncytial virus bronchiolitis had a strong relationship with recurrent wheezing (RR 2.6; 95% confidence interval, CI, 2.2, 3.1), but a relative modest PAR (8%; 95% CI 6, 11%) which can be explained by a low prevalence (13%). Day-care attendance showed a strong relationship with recurrent wheezing (RR 1.9; 95% CI 1.7, 2.2) and the highest PAR (32%; 95% CI 23, 37%) due to a high prevalence (67%). The combined adjusted PAR for the 14 risk factors associated with recurrent wheezing was 49% (95% CI 46, 52%). CONCLUSIONS: In moderate preterm infants, day-care attendance has the largest PAR for recurrent wheezing. Trial evidence is needed to determine the potential benefit of delayed day-care attendance in this population. PMID- 27199200 TI - Predictors of Hospital Length of Stay and Readmissions in Ischemic Stroke Patients and the Impact of Inpatient Medication Management. AB - OBJECTIVE: This study was designed to evaluate predictors of hospital length of stay (LOS) and readmissions among nonsurgical ischemic stroke patient, and the impact of inpatient medication management. METHODS: This retrospective cohort study includes adult patients (>=18 years) hospitalized with a diagnosis of nonsurgical ischemic stroke from November 2007 to March 2013. In November 2011, an inpatient medication management model was implemented in the stroke unit. At the end of the study period, patients were matched before and after implementation of the inpatient medication management model (non-PHC [pharmacist hospitalist collaborative] and PHC, respectively) to evaluate change in outcomes. The primary outcome of the study is an evaluation of predictive factors affecting LOS and readmissions. Additionally, changes in LOS and all-cause readmission at 30, 60, and 90 days when compared between PHC and non-PHC were evaluated. FINDINGS: A total of 151 PHC patients were matched to 248 non-PHC patients. There was no difference in LOS between the PHC and non-PHC patients (mean adjusted difference -.14; P = .66). Similar finding was observed for readmissions (P > .05). Insurance type was a significant predictor of LOS, with Medicare patients having an extended LOS compared to patients with private insurance (mean difference -1.00; P = .005). Patients taking statins and patients aged less than 80 years had a lower 30-day readmission rate compared to nonstatin users and patients aged 80 years or older, respectively (P < .05). CONCLUSIONS: Insurance type and severity of illness are important predictors of LOS, whereas readmissions are mostly influenced by age and statin use. PMID- 27199201 TI - Analysis of Factors Associated with Progression and Long-Term Outcomes of Penetrating Artery Territory Infarction: A Retrospective Study. AB - BACKGROUND: Patients with penetrating artery territory infarction occasionally show progressive motor deficits during the acute stage with poor prognosis. Predictive indices or medical therapies for suppressing the symptomatic progression (SP) of penetrating artery infarction have not been established. In this study, we investigated SP-related clinical factors and functional outcomes, specifically improvement 3 months post ictus in patients with penetrating artery infarction. METHODS: We retrospectively examined acute stroke patients with penetrating artery infarction admitted at 7 collaborative hospitals. SP was defined as an increase by 1 point or higher in the National Institutes of Health Stroke Scale score. Functional improvement was assessed based on the modified Rankin Scale at 3 months. The influence of factors, such as patient characteristics, clinical data, medical treatment during the acute stage and on SP, and functional improvement was statistically analyzed. RESULTS: Four hundred eighty-eight patients (310 men; mean age, 70 years) were examined. Sixty-eight patients (14%) exhibited SP. Multivariate logistic regression analysis revealed that higher hemoglobin A1c (odds ratio [OR], 1.30; 95% confidence interval [CI], 1.10-1.55), body mass index (BMI; OR, .85; 95% CI, .77-.94), and systolic blood pressure on admission (OR, 1.63; 95% CI, 1.19-2.25) were independent predictors of SP in penetrating artery infarction. Dual antiplatelet therapy (DAPT; OR, 3.48; 95% CI, 1.52-8.38) independently influenced functional improvement. CONCLUSIONS: Initial high blood pressure, diabetes, and low BMI on admission were associated with early progression of penetrating artery infarction. DAPT during the acute stage may contribute to functional improvement. PMID- 27199203 TI - Thromboembolism in adults with primary immune thrombocytopenia: a systematic literature review and meta-analysis. AB - Adults with primary immune thrombocytopenia (ITP) may be susceptible to thromboembolism (TE). The objective of this systematic review was to evaluate studies that reported the prevalence and risk of developing TE in the ITP population from ITP diagnosis and splenectomy. We searched several bibliographic databases and included 29 studies. Using meta-analytical techniques, the pooled prevalence of TE before ITP diagnosis was 7.84% (arterial 6.25%; venous 1.95%). The pooled 'annualised' cumulative incidence (without prior TE) and cumulative risk (irrespective of prior TE) were 1.29%/yr and 3.00%/yr, respectively. Splenectomised patients had pooled cumulative risk of arterial TE (ATE) and venous TE (VTE) of 0.19%/yr and 1.10%/yr, respectively. In cohorts, regardless of a history of TE, the pooled relative risk (RR) of any TE was 1.60 (1.34, 1.86) for ITP vs. ITP-free individuals [arterial: 1.52 (1.25, 1.80); venous: 1.70 (0.96, 2.43)]. Splenectomised patients were at higher risk of venous events, pooled RR 2.39 (1.61, 3.17). To conclude, we found an increased risk of TE (mainly ATE) among ITP individuals and a higher risk of VTEs after splenectomy. How intrinsic (ITP pathophysiology, age, gender) and extrinsic factors (treatment) contribute to this risk could not be investigated here but is a task for future studies. PMID- 27199202 TI - Pharmacokinetic investigations of the marker active metabolites 4-methylamino antipyrine and 4-amino-antipyrine after intramuscular injection of metamizole in healthy piglets. AB - Metamizole (MT) is a pyrazolone nonsteroidal anti-inflammatory drug labelled for humans and animals. The aim of this study was to assess the pharmacokinetics of its active metabolites 4-methylamino-antipyrine (MAA) and 4-amino-antipyrine (AA) in male piglets after a single intramuscular injection of MT. Eight healthy male piglets were administered MT (100 mg/kg) intramuscularly. Blood was sampled at scheduled time intervals, and drug plasma concentrations evaluated by a validated HPLC method. MAA and AA plasma concentrations were quantitatively detectable from 0.25 to 48 h and 0.50 to 72 h, respectively, in 6 of 8 and 7 of 8 animals. The average maximum concentrations of MAA and AA were of 47.59 and 4.94 mg/mL, respectively. The average half-lives were 8.57 and 13.3 h for MAA and AA, respectively. This study showed that the amount of MAA and AA produced in piglets is different to that in the animal species previously investigated. Further studies are necessary to understand whether these differences in MAA and AA plasma concentrations between animal species necessitate diverse therapeutic drug dosing. PMID- 27199197 TI - Electronic Health Records: Then, Now, and in the Future. AB - OBJECTIVES: Describe the state of Electronic Health Records (EHRs) in 1992 and their evolution by 2015 and where EHRs are expected to be in 25 years. Further to discuss the expectations for EHRs in 1992 and explore which of them were realized and what events accelerated or disrupted/derailed how EHRs evolved. METHODS: Literature search based on "Electronic Health Record", "Medical Record", and "Medical Chart" using Medline, Google, Wikipedia Medical, and Cochrane Libraries resulted in an initial review of 2,356 abstracts and other information in papers and books. Additional papers and books were identified through the review of references cited in the initial review. RESULTS: By 1992, hardware had become more affordable, powerful, and compact and the use of personal computers, local area networks, and the Internet provided faster and easier access to medical information. EHRs were initially developed and used at academic medical facilities but since most have been replaced by large vendor EHRs. While EHR use has increased and clinicians are being prepared to practice in an EHR-mediated world, technical issues have been overshadowed by procedural, professional, social, political, and especially ethical issues as well as the need for compliance with standards and information security. There have been enormous advancements that have taken place, but many of the early expectations for EHRs have not been realized and current EHRs still do not meet the needs of today's rapidly changing healthcare environment. CONCLUSION: The current use of EHRs initiated by new technology would have been hard to foresee. Current and new EHR technology will help to provide international standards for interoperable applications that use health, social, economic, behavioral, and environmental data to communicate, interpret, and act intelligently upon complex healthcare information to foster precision medicine and a learning health system. PMID- 27199204 TI - [Determinants of controlled hypertension in patients treated with antihypertensive drugs in France: The French League Against Hypertension Survey (FLAHS 2015)]. AB - OBJECTIVE: The FLASH 2015 survey sought the determinants of hypertension control in subjects treated with antihypertensive drugs in France. METHOD: Sending self administered questionnaire by mail to a representative sample of the population living in metropolitan France (MetaScope basis, TNS Sofres, France). Patients who declare taking antihypertensive drugs are considered treated hypertensives. A home blood pressure monitoring during 3 days was asked in subjects owing a blood pressure monitor and the average of 18 measurements was calculated. RESULTS: A total of 6379 subjects aged 55 and older were included with 2814 (44.1%) treated with antihypertensive drugs. Home blood pressure was obtained from 1455 subjects including 882 (60.6%) treated. SBP/DBP are 129.3+/-13.5/75.5+/-9.0mmHg and are higher in treated subjects in each age category. BP<135/85 was observed in 55.4% and BP<140/90 in 71.7%. Determinants of BP control (<135/85) are the number of measurement for averaging (18 measures over 3 days vs 3 measurements on a morning; 55.4%/44.3%), age (55-64 years vs 80 years old; 57.6%/49.1%), gender (women vs men; 60.3%/50.1%), BMI (<25 vs >30; 63.1%/46.1%). In the 80 and older, a SBP<145 was observed in 74.7% of subjects. The control was 61% when considering an SBP/DBP<135/85 in 55-79 years and SBP<145 among 80 and older. CONCLUSION: The control of hypertension evaluated by home blood pressure on a representative population living in metropolitan France is estimated at between 44.3% and 74.7% and several determinants influence the control of blood pressure like age, gender and BMI. PMID- 27199206 TI - On Shermer on morality. AB - This is my critical commentary on Michael Shermer's paper "Morality is real, objective, and natural." Shermer and I agree that morality is both real and objective. Here I raise serious reservations about both Shermer's account of where morality comes from and his account of what morality tells us to do. His approach to the foundations of morality would allow some very disturbing behaviors to count as moral, and his approach to what morality says does not provide the action guidance we need from a moral theory. PMID- 27199207 TI - [Coronary artery disease in women: True specificities to know in order to improve management and outcome]. AB - Coronary artery disease is the leading death for women in Europe and developed countries. It kills seven times more than breast cancer. The number of deaths from coronary artery disease increase and affects also younger women (< 55 years old). Coronary artery disease in women is a major public health problem, often underestimated. Women should become a priority target of prevention. Traditional vision of coronary artery disease as myocardial ischemia due to obstruction of major coronary arteries do not represent all the aspects of ischemic disease in women. Myocardial ischemia without obstruction of major coronary arteries, described as microvascular dysfunction is often unknown and ignored. It is yet a situation at high cardiovascular risk. Presentation and symptoms of coronary artery disease are misleading in women. Coronary artery disease in women remains under-diagnosed and under-treated. It is necessary to improve management of women at cardiovascular risk, whose inequalities contribute to the excess of female mortality from coronary artery disease. Coronary artery disease in women needs new diagnostic and therapeutic approaches. It must take into account specific risk stratification, evaluation of particular chest pain and reduced performance of non-invasive testing. PMID- 27199205 TI - A key role for the N/OFQ-NOP receptor system in modulating nicotine taking in a model of nicotine and alcohol co-administration. AB - Alcohol and nicotine are often co-abused. Although the N/OFQ-NOP receptor system is considered a potential target for development of drug abuse pharmacotherapies, especially for alcoholism, little is known about the role of this system in nicotine dependence. Furthermore, the effect of prior history of nicotine dependence on subsequent nicotine and alcohol taking is understudied. Using an operant co-administration paradigm, in which rats concurrently self-administer nicotine and alcohol, we found that nicotine dependent rats increased nicotine self-administration over time as compared to non-dependent animals, while patterns of alcohol lever pressing did not change between groups. Pretreatment with the potent NOP receptor agonist AT-202 (0.3-3 mg/kg) increased nicotine lever pressing of both dependent and non-dependent groups, whereas the selective antagonist SB612111 (1-10 mg/kg) elicited a clear reduction of nicotine responses, in both dependent and non-dependent rats. In parallel, AT-202 only produced minor changes on alcohol responses and SB612111 reduced alcohol taking at a dose that also reduced locomotor behavior. Results indicate that a history of nicotine dependence affects subsequent nicotine- but not alcohol-maintained responding, and that NOP receptor antagonism, rather than agonism, blocks nicotine self-administration, which strongly suggests a critical role for the endogenous N/OFQ in the modulation of nicotine reinforcement processes. PMID- 27199209 TI - Identification of a novel HLA-A*02 variant, HLA-A*02:614, in a Taiwanese individual. AB - One nucleotide substitution at residue 806 of HLA-A*02:01:01:01 results in a new allele, HLA-A*02:614. PMID- 27199208 TI - Real-world surgical outcomes of a gelatin-hemostatic matrix in women requiring a hysterectomy: a matched case-control study. AB - INTRODUCTION: The aim of this study was to compare adverse events and surgical outcomes of hysterectomy with or without use of a gelatin-hemostatic matrix (SURGIFLO((r)) ). MATERIALS AND METHODS: Prospective case-control study (Canadian Task Force classification II2) of total hysterectomy (Piver Type 1) provided by surgeons in Australia between November 2005 and May 2015. Data were collected via SurgicalPerformance, a web-based data project which aims to provide confidential feedback to surgeons about their surgical outcomes. Of 2440 records of women who received a hysterectomy, 1351 were eligible for these analyses; 107 received SURGIFLO((r)) hemostatic matrix to prevent postoperative blood loss and 1244 did not. RESULTS: Patients with or without SURGIFLO((r)) differed in age, Charlson comorbidity index, and American Society of Anesthesiologists physical status classification system score (ASA), and also differed in clinical outcomes. After matching for patient's age and ASA at surgery, patients with and without SURGIFLO((r)) had comparable baseline characteristics. Matched patients with and without SURGIFLO((r)) had comparable clinical outcomes including risk of developing vault hematoma, return to the operating room, transfusion of red cells, surgical site infection (pelvis), readmission within 30 days and unplanned ICU admission. CONCLUSIONS: In a sample matched by age and ASA, SURGIFLO((r)) neither prevented nor caused additional adverse events in women undergoing hysterectomy. Surgeons used SURGIFLO((r)) more commonly among women who were older, had more comorbidities and a higher ASA score. This indicates that it may be most useful in complicated surgery or cases. PMID- 27199210 TI - Microwave temperature measurement in microfluidic devices. AB - In spite of various existing thermometry methods for microfluidic applications, it remains challenging to measure the temperature of individual droplets in segmented flow since fast moving droplets do not allow sufficient exposure time demanded by both fluorescence based techniques and resistance temperature detectors. In this contribution, we present a microwave thermometry method that is non-intrusive and requires minimal external equipment. This technique relies on the correlation of fluid temperature with the resonance frequency of a microwave sensor that operates at a GHz frequency range. It is a remote yet direct sensing technique, eliminating the need for mixing fluorescent dyes with the working fluid. We demonstrated that the sensor operates reliably over multiple tests and is capable of both heating and sensing. It measures temperature to within +/-1.2 degrees C accuracy and can detect the temperature of individual droplets. PMID- 27199212 TI - Prediction of the risk of cesarean delivery after labor induction in twin gestations based on clinical and ultrasound parameters. AB - AIMS: To develop a model based on clinical and ultrasound parameters to predict the risk of cesarean delivery after labor induction in near-term twin gestations. METHODS: This retrospective cohort study included 189 consecutive women with twin gestations at >= 36.0 weeks scheduled for labor induction. The Bishop score and transvaginal ultrasonographic measurements of cervical length were obtained immediately before labor induction. Parameters studied included maternal age, height, weight, parity, gestational age, Bishop score, cervical length, epidural analgesia, method of conception, chorionicity and birth weight. Prostaglandin E2 (dinoprostone) and oxytocin were used for labor induction. Logistic regression analysis and receiver operating characteristic curve were used to generate a predictive model for cesarean delivery. RESULTS: Fifty (26.5%) of the 189 women had cesarean deliveries. According to logistic regression analysis, maternal height (P = 0.004), parity (P = 0.005) and cervical length (P = 0.016), but not Bishop score (P = 0.920), were identified as independent predictors of cesarean delivery. A risk score based on a model of these three parameters was calculated for each patient. The model was shown to have an adequate goodness of fit (P = 0.201) and the area under the curve was 0.722, indicating fairly good discrimination. CONCLUSIONS: Maternal height, parity and cervical length were independent parameters for predicting the risk of cesarean delivery after labor induction in twin gestations. A predictive model using these parameters may provide useful information for deciding whether or not to induce labor. PMID- 27199211 TI - Fabrication, characterization, and in vitro evaluation of silver-containing arabinoxylan foams as antimicrobial wound dressing. AB - Arabinoxylan ferulate (AXF) foams were fabricated via enzymatic peroxidase/hydrogen peroxide crosslinking reaction followed by freeze-drying and studied as a potential wound dressing material. The AXF foam's rheological, morphological, porous, and swelling properties were examined. AXF foams were found to be a viscoelastic material that proved to be highly porous and water absorbent. AXF foams possessed low endotoxin levels and were cytocompatible with fibroblasts. Silver was successfully integrated into AXF foams and slowly released over 48 h. AXF foams impregnated with silver demonstrated efficacy inhibiting bacterial growth according to a modified Kirby-Bauer disk diffusion susceptibility test. Overall, AXF foams possess appropriate material properties and the silver-loaded AXF foams showed antimicrobial activity necessary to be a candidate material in wound dressing development. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2456-2465, 2016. PMID- 27199213 TI - Efficacy and Safety of Percutaneous Left Atrial Appendage Occlusion for Stroke Prevention in Nonvalvular Atrial Fibrillation: A Meta-analysis of Contemporary Studies. AB - BACKGROUND: Percutaneous left atrial appendage (LAA) occlusion has emerged as an important treatment for patients with nonvalvular atrial fibrillation (NVAF) who are at high stroke risk and have contraindications for anticoagulation. However, literature about the efficacy and safety of LAA occlusion is minimal to date. We performed a meta-analysis to assess the rates of stroke events and adverse events for patients treated with occlusion devices. METHODS: We conducted a comprehensive search on PubMed, Web of Science, OVID, SCOPUS databases and the Cochrane Central Register of Controlled Trials databases from inception to December 31, 2014 for studies of percutaneous LAA occlusion for patients with NVAF. Studies were included in the meta-analysis if at least 10 patients were studied with six months or more of follow-up period and reported at least one outcome of interest. RESULTS: A total of 2779 patients in 25 studies were included in the meta-analysis. Two were randomised control trials (RCTs), others were cohort studies. The adjusted incidence rate of stroke was 1.2/100 person years (PY) (95% confidence interval [CI], 0.9-1.6/100 PY). The ischaemic and haemorrhagic stroke rates were 1.1/100 PY (95% CI, 0.8-1.4/100 PY) and 0.2/100 PY (95% CI, 0.1-0.3/100 PY), respectively. The combined efficacy outcomes (stroke or transient ischaemic attacks [TIAs], systemic embolism, or cardiovascular death) was 2.7/100 PY (95% CI, 1.9- 3.4/100 PY). Major bleeding and pericardial effusions were the most commonly observed adverse events at a rate of 2.6% (95% CI, 1.5%-3.6%) and 2.5% (95% CI, 1.8%-3.2%), respectively. CONCLUSIONS: Percutaneous LAA occlusion is a reasonably efficacious and safe therapeutic option in patients with NVAF who are at high risk for stroke and contraindicated for long-term anticoagulation. PMID- 27199214 TI - Eosinophil progenitor levels are increased in patients with active pediatric eosinophilic esophagitis. PMID- 27199215 TI - Growth responses of Ulva prolifera to inorganic and organic nutrients: Implications for macroalgal blooms in the southern Yellow Sea, China. AB - The marine macrophyte Ulva prolifera is the dominant green-tide-forming seaweed in the southern Yellow Sea, China. Here we assessed, in the laboratory, the growth rate and nutrient uptake responses of U. prolifera to different nutrient treatments. The growth rates were enhanced in incubations with added organic and inorganic nitrogen [i.e. nitrate (NO3(-)), ammonium (NH4(+)), urea and glycine] and phosphorus [i.e. phosphate (PO4(3-)), adenosine triphosphate (ATP) and glucose 6-phosphate (G-6-P)], relative to the control. The relative growth rates of U. prolifera were higher when enriched with dissolved organic nitrogen (urea and glycine) and phosphorus (ATP and G-6-P) than inorganic nitrogen (NO3(-) and NH4(+)) and phosphorus (PO4(3-)). In contrast, the affinity was higher for inorganic than organic nutrients. Field data in the southern Yellow Sea showed significant inverse correlations between macroalgal biomass and dissolved organic nutrients. Our laboratory and field results indicated that organic nutrients such as urea, glycine and ATP, may contribute to the development of macroalgal blooms in the southern Yellow Sea. PMID- 27199216 TI - Magnetic Core-Shell Silica Nanoparticles with Large Radial Mesopores for siRNA Delivery. AB - A novel type of magnetic core-shell silica nanoparticles is developed for small interfering RNA (siRNA) delivery. These nanoparticles are fabricated by coating super-paramagnetic magnetite nanocrystal clusters with radial large-pore mesoporous silica. The amine functionalized nanoparticles have small particle sizes around 150 nm, large radial mesopores of 12 nm, large surface area of 411 m(2) g(-1) , high pore volume of 1.13 cm(3) g(-1) and magnetization of 25 emu g( 1) . Thus, these nanoparticles possess both high loading capacity of siRNA (2 wt%) and strong magnetic response under an external magnetic field. An acid liable coating composed of tannic acid can further protect the siRNA loaded in these nanoparticles. The coating also increases the dispersion stability of the siRNA-loaded carrier and can serve as a pH-responsive releasing switch. Using the magnetic silica nanoparticles with tannic acid coating as carriers, functional siRNA has been successfully delivered into the cytoplasm of human osteosarcoma cancer cells in vitro. The delivery is significantly enhanced with the aid of the external magnetic field. PMID- 27199217 TI - Tumor regression grade in gastric cancer: Predictors and impact on outcome. AB - BACKGROUND: The clinical value and prognostic implications of histologic response to neoadjuvant chemotherapy in gastric cancer is unknown. METHODS: Tumor regression grade (TRG) was recorded in 58 gastric cancer patients identified from two institutional surgical databases. TRG 1a/b represented histologic responders (<10% viable tumor), while TRG 2/3 represented non-responders (>10% viable tumor). RESULTS: TRG 1a/b was recorded in 10 patients (17%), while 48 patients (83%) had a TRG 2/3 response. Larger tumor size (OR 0.24; 95%CI 0.09, 0.64; P = 0.004) and clinical downstaging (OR 30.0; 95%CI 3.26, 276; P = 0.003) were the only factors predictive of histologic response. TRG 1a/b responders had 3-year survival of 70.0% and an estimated overall survival of >69.8 months compared to 38.2% and 22.8 months in non-responders; however, this trend was not statistically significant (P = 0.535). While TRG could not predict survival (OR 2.40; 95%CI 0.46, 12.57; P = 0.300), patient age (OR 1.06; 95%CI 1.00, 1.11; P = 0.035), and the number of positive lymph nodes (>=7; OR 0.05; 95%CI 0.07, 0.27; P < 0.001) were independent predictors of survival. CONCLUSIONS: Few gastric cancers demonstrate histologic response to neoadjuvant chemotherapy. While TRG may be a valid marker for treatment response, its predictive value and clinical application in gastric cancer remains unclear. J. Surg. Oncol. 2016;114:434-439. (c) 2016 Wiley Periodicals, Inc. PMID- 27199218 TI - Genomic evidence for ecological divergence against a background of population homogeneity in the marine snail Chlorostoma funebralis. AB - The balance between natural selection, gene flow and genetic drift is difficult to resolve in marine invertebrates with extensive dispersal and fluctuating population sizes. The intertidal snail Chlorostoma funebralis has planktonic larvae and previous work using mtDNA polymorphism reported no genetic population structure. Nevertheless, recent studies have documented differences in thermal tolerance and transcriptomic responses to heat stress between northern and southern California, USA, populations. To gain insight into the dynamics influencing adaptive divergence, we used double-digest restriction site associated DNA (ddRAD) sequencing to identify 1861 genomewide, quality-filtered single-nucleotide polymorphism (SNP) loci for C. funebralis collected from three northern and three southern California sites (15 individuals per population). Considering all SNPs, there was no evidence for genetic differentiation among populations or regions (average FST = 0.0042). However, outlier tests revealed 34 loci putatively under divergent selection between northern and southern populations, and structure and SNP tree analyses based on these outliers show clear genetic differentiation between geographic regions. Three of these outliers are known or hypothesized to be involved in stress granule formation, a response to environmental stress such as heat. Combined with previous work that found thermally tolerant southern populations show high baseline expression of stress response genes, these results further suggest that thermal stress is a strong selective pressure across C. funebralis populations. Overall, this study increases our understanding of the factors constraining local adaptation in marine organisms, while suggesting that ecologically driven, strong differentiation can occur at relevant loci in a species with planktonic larvae. PMID- 27199219 TI - Trastuzumab-targeted gene delivery to Her2-overexpressing breast cancer cells. AB - We describe a novel gene delivery system that specifically targets human epidermal growth factor receptor 2 (Her2)-overexpressing breast cancer cells. The targeting complexes consist of a PEGylated polylysine core that is bound to DNA molecules coding for either green fluorescent protein or shrimp luciferase. The complex is disulfide linked to the monoclonal antibody trastuzumab and to a pore forming protein, Listeriolysin O (LLO). Trastuzumab is responsible for specific targeting of Her2 receptors and uptake of the gene delivery complex into endosomes of recipient cells, whereas LLO ensures that the DNA molecules are capable of transit from the endosomes into the cytoplasm. Omission of either trastuzumab or LLO from the nanocomplexes results in minimal gene product in targeted cells. Treatment of isogeneic MCF7 and MCF7/Her18 cell lines, differing only in number of Her2 receptors, with the complete gene delivery system results in a 30-fold greater expression of luciferase activity in the Her2-overexpressing MCF7/Her18 cells. Our nanocomplexes are small (150-250 nm), stable to storage, nontoxic and generic in make-up such that any plasmid DNA or antibody specific for cell-surface receptors can be coupled to the PEGylated polylysine core. PMID- 27199220 TI - Locked nucleic acid inhibits miR-92a-3p in human colorectal cancer, induces apoptosis and inhibits cell proliferation. AB - MicroRNAs (miRNAs) are a type of small noncoding RNAs that have a vital role in basic biological processes such as cellular growth, division and apoptosis. A change in the expression of miRNAs can induce many diseases. Recently, the role of miRNA in some of the cancers as a tumor suppressor and oncogene has been recognized. Several studies have proved that miR-92a-3p acts as an oncogene in colorectal cancer (CRC). We studied CRC by inhibiting miR-92a-3p in SW48 cells (human colorectal cancer cell line) that were transfected with locked nucleic acid (LNA). At different times, the expression level of miR-92a-3p, cell vitality, apoptosis and necrosis were studied by qRT-PCR, MTT, Annexin-V and propidiumiodide. Our results showed that the expression of miR-92a-3p and proliferation of SW48 cells were decreased, and also a high percentage of SW48 cells were exposed to apoptosis and necrosis (P?0.005). Our study showed that the inhibition of miR-92a-3p with LNA inhibited cell proliferation and induced apoptosis and necrosis in CRC. PMID- 27199221 TI - Tumor radiosensitization by gene therapy against endoglin. AB - Gene electrotransfer of plasmid encoding shRNA against endoglin exerts antitumor efficacy, predominantly by vascular targeted effect. As vascular targeting therapies can promote radiosensitization, the aim of this study was to explore this gene therapy approach with single and split dose of irradiation in an endoglin non-expressing TS/A mammary adenocarcinoma tumor model to specifically study the vascular effects. Intratumoral gene electrotransfer of plasmids encoding shRNA against endoglin, under the control of a constitutive or tissue specific promoter for endothelial cells, combined with a single or three split doses of irradiations was evaluated for the antitumor efficacy and histologically. Both plasmids proved to be equally effective in tumor radiosensitization with 40-47% of tumor cures. The combined treatment induced a significant decrease in the number of blood vessels and proliferating cells, and an increase in levels of necrosis, apoptosis and hypoxia; therefore, the antitumor efficacy was ascribed to the interaction of vascular targeted effect of gene therapy with irradiation. Endoglin silencing by the shRNA technology, combined with electrotransfer and the use of a tissue-specific promoter for endothelial cells, proved to be a feasible and effective therapeutic approach that can be used in combined treatment with tumor irradiation. PMID- 27199223 TI - Putting Meaning into Meaningful Use: A Roadmap to Successful Integration of Evidence at the Point of Care. AB - Pressures to contain health care costs, personalize patient care, use big data, and to enhance health care quality have highlighted the need for integration of evidence at the point of care. The application of evidence-based medicine (EBM) has great promise in the era of electronic health records (EHRs) and health technology. The most successful integration of evidence into EHRs has been complex decision tools that trigger at a critical point of the clinical visit and include patient specific recommendations. The objective of this viewpoint paper is to investigate why the incorporation of complex CDS tools into the EMR is equally complex and continues to challenge health service researchers and implementation scientists. Poor adoption and sustainability of EBM guidelines and CDS tools at the point of care have persisted and continue to document low rates of usage. The barriers cited by physicians include efficiency, perception of usefulness, information content, user interface, and over-triggering. Building on the traditional EHR implementation frameworks, we review keys strategies for successful CDSs: (1) the quality of the evidence, (2) the potential to reduce unnecessary care, (3) ease of integrating evidence at the point of care, (4) the evidence's consistency with clinician perceptions and preferences, (5) incorporating bundled sets or automated documentation, and (6) shared decision making tools. As EHRs become commonplace and insurers demand higher quality and evidence-based care, better methods for integrating evidence into everyday care are warranted. We have outlined basic criteria that should be considered before attempting to integrate evidenced-based decision support tools into the EHR. PMID- 27199224 TI - Fluoride: a risk factor for inflammatory bowel disease? AB - Although the association between inflammatory bowel disease (IBD) and oral hygiene has been noticed before, there has been little research on prolonged fluoride exposure as a possible risk factor. In the presented cases, exposure to fluoride seems indirectly associated with higher incidence of IBD. Fluoride toxicology and epidemiology documents frequent unspecific chronic gastrointestinal symptoms and intestinal inflammation. Efflux genes that confer resistance to environmental fluoride may select for IBD associated gut microbiota and therefore be involved in the pathogenesis. Together these multidisciplinary results argue for further investigation on the hypothesis of fluoride as a risk factor for IBD. PMID- 27199222 TI - Tumor-associated GM-CSF overexpression induces immunoinhibitory molecules via STAT3 in myeloid-suppressor cells infiltrating liver metastases. AB - Assumptions that liver immune cells and immunosuppressive pathways are similar to their counterparts in other spaces have led to gaps in our understanding of intrahepatic neoplasm aggressiveness. Myeloid-derived suppressor cells (MDSCs) are potent inhibitors of antitumor immunity and pose a major obstacle to solid tumor treatment. Liver MDSCs (L-MDSCs) associated with liver metastases (LM) are particularly problematic by contributing to intrahepatic immunosuppression that promotes tumor progression. L-MDSCs have been reported to expand in response to granulocyte-macrophages colony-stimulating factor (GM-CSF) and suppress antitumor immunity in LM. To extend these findings, we examined mechanisms of intrahepatic immunosuppression exploited by L-MDSCs. We found that the majority of L-MDSCs co expressed GM-CSF receptor (GM-CSF-R), indoleamine 2,3-dioxygenase (IDO) and programmed death ligand 1 (PD-L1), while demonstrating high levels of signal transducer and activator of transcription factor 3 (STAT3) activation. GM-CSF secreting tumor cells induced STAT3 phosphorylation in L-MDSCs in addition to expression of IDO and PD-L1. GM-CSF or GM-CSF-R blockade markedly reduced L-MDSC IDO and PD-L1 expression, implicating tumor-derived GM-CSF in supporting L-MDSC immunoinhibitory molecule expression. Small-molecule inhibitors of Janus activated kinase 2 (JAK2) and STAT3 also dramatically diminished IDO and PD-L1 expression in L-MDSCs. We determined that STAT3 exerts transcriptional control over L-MDSC IDO and PD-L1 expression by binding to the IDO1 and PD-L1 promoters. Our data suggest that the GM-CSF/JAK2/STAT3 axis in L-MDSCs drives immunosuppression in a model of LM and blockade of this pathway may enable rescue of intrahepatic antitumor immunity. PMID- 27199225 TI - Visible Light Initiated Hantzsch Synthesis of 2,5-Diaryl-Substituted Pyrroles at Ambient Conditions. AB - Irradiation of a mixture of enamines and alpha-bromo ketones, with a catalytic amount of Ir(ppy)3 by visible light (lambda = 450 nm), enables the production of various 2,5-diaryl-substituted pyrroles in good to excellent yields. The key intermediates in this reaction have been identified as alkyl radicals, generated from single-electron transfer from the photoexcited Ir(ppy)3* to alpha-bromo ketones, which subsequently react with a broad range of enamines to undergo the Hantzsch reaction rapidly at ambient conditions. PMID- 27199226 TI - Numerical Study on Behavior of Groundwater Flow in Single Rough Fractures Under Mechanical Effect. AB - This paper numerically investigates the characteristics of groundwater flow in spatially correlated variable aperture fractures under the mechanical effect. Spatially correlated aperture distributions are generated using the geostatistical method (i.e., turning bands algorithm in this study). To represent a nonlinear relationship between the effective normal stress and the fracture aperture, a simple mechanical formula is combined with a local flow model. Numerical results indicate that the groundwater flow is significantly affected by the geometry of aperture distribution, varying with the applied effective normal stress as well as the spatial correlation length of aperture distribution. Moreover, using the flow results simulated in this study, two empirical formulae are proposed: (1) the first one (modified Louis formula) is to represent the relationship between the effective normal stress and the effective permeability of fracture and (2) the second one is to represent the relationship between relative roughness and effective permeability. PMID- 27199227 TI - Vibrio algivorus sp. nov., an alginate- and agarose-assimilating bacterium isolated from the gut flora of a turban shell marine snail. AB - An agarose- and alginate-assimilating, Gram-reaction-negative, non-motile, rod shaped bacterium, designated strain SA2T, was isolated from the gut of a turban shell sea snail (Turbo cornutus) collected near Noto Peninsula, Ishikawa Prefecture, Japan. The 16S rRNA gene sequence of strain SA2T was 99.59 % identical to that of Vibrio rumoiensis DSM 19141T and 98.19 % identical to that of Vibrio litoralis DSM 17657T. This suggested that strain SA2T could be a subspecies of V. rumoiensis or V. litoralis. However, DNA-DNA hybridization results showed only 37.5 % relatedness to DSM 19141T and 44.7 % relatedness to DSM 17657T, which was far lower than the 70 % widely accepted to define common species. Strain SA2T could assimilate agarose as a sole carbon source, whereas strains DSM 19141T and DSM 17657T could not assimilate it at all. Furthermore, results using API 20NE and API ZYM kits indicated that their enzymic and physiological phenotypes were also different. These results suggested that strain SA2T represented a novel species within the genus Vibrio. The major isoprenoid quinone in SA2T was Q-8, and its major polar lipids were phosphatidylethanolamine and phosphatidylglycerol. The major fatty acids were summed feature 3, (comprising C16 : 1omega6c and/or C16 : 1omega7c), C16 : 0, and summed feature 8 (comprising C18 : 1omega6c and/or C18 : 1omega7c). The DNA G+C content of SA2T was 40.7 mol%. The name proposed for this novel species of the genus Vibrio is Vibrio algivorus sp. nov., with the type strain designated SA2T (=DSM 29824T=NBRC 111146T). PMID- 27199228 TI - Diagnosis and treatment of cardiac echinococcosis. AB - Cardiac echinococcosis is a rare manifestation of cystic echinococcosis (CE) caused by the tapeworm Echinococcus granulosus Among all patients suffering from CE, only 0.5%-2% exhibit a cardiac involvement. In addition, during the past years the number of CE cases reported in Western Europe remained roughly unchanged. However, we postulate that cases of CE in Western Europe will increase due to a growing number of refugees coming from endemic areas such as Southern Europe, Eastern Europe and the Middle East. Importantly, although cardiac echinococcosis is rare the disease can lead to many clinical complications, for instance acute heart failure and life-threatening arrhythmias. With respect to the increasing relevance of cardiac echinococcosis in Western Europe and the danger of fulminant disease courses, here we review diagnosis strategies and treatment options of the disease. Diagnosis of cardiac echinococcosis requires a detailed evaluation of the patients' case history, specific laboratory analyses and radiological imaging methods. Ultrasound, MRI and CT are key imaging tools for diagnosis, therapy control, prognosis estimation and disease course control. For the therapy of cardiac echinococcosis, a combination of surgical removal and drug treatment should be applied to symptomatic as well as asymptomatic patients. The complete surgical removal of the cyst(s) is the major prognosis factor of the cardiac manifestation of CE. PMID- 27199229 TI - Ethosomes and Transfersomes: Principles, Perspectives and Practices. AB - BACKGROUND: The success story of liposomes in the treatment of systemic infectious diseases and various carcinomas lead the scientists to the innovation of elastic vesicles to achieve similar success through transdermal route. In this direction, ethosomes and transfersomes were developed with the objective to design the vesicles that could pass through the skin. However, there is a lack of systematic review outlining the principles, method of preparation, latest advancement and applications of ethosomes and transfersomes. This review covers various aspects that would be helpful to scientists in understanding advantages of these vesicular systems and designing a unique nano vesicular delivery system. METHODS: Structured search of bibliographic databases for previously published peer-reviewed research papers was explored and data was culminated in terms of principle of these vesicular delivery systems, composition, mechanism of actions, preparation techniques, methods for their characterization and their application. RESULTS: A total of 182 papers including both, research and review articles, were included in this review in order to make the article comprehensive and readily understandable. The mechanism of action and composition of ethosomes and transfersomes was extensively discussed. Various methods of preparation such as, rotary film evaporation method, reverse phase evaporation method, vortex/ sonication method, ethanol injection method, freeze thaw methods, along with their advantages has been discussed. It was also discussed that both these elastic nanocarriers offer unique advantages of ferrying the drug across membranes, sustaining drug release as well as protecting the encapsulated bio actives from external environment. The enhanced bioavailability and skin penetration of ethosomes as compared to conventional vesicular delivery systems is attributed to the presence of ethanol in the bilayers while that for transfersomes accrues due to their elasticity along with their ability to retain their shape because of the presence of edge activators. Successful delivery of synthetic drugs as well as phytomedicines has been extensively reported through these vesicles. CONCLUSION: Though these vesicular systems offer a good potential for rational drug delivery, a thoughtfully designed process is required to optimize the process variables involved. Industrial scale production of efficacious, safe, cost effective and stable formulations of both these delivery systems appears to be a pre-requisite to ensure their utility as the trans-dermal vehicles. PMID- 27199230 TI - Photothermal Ablation of Cancer Cells Using Folate-Coated Gold/ Graphene Oxide Composite. AB - OBJECTIVE: A new tumor targeted polymer-coated gold/graphene hybrid has been developed for achieving simultaneously thermoablation and chemoterapy of folate receptor-positive cancer cells. METHODS: The gold/graphene hybrid was prepared by depositing gold nanospheres onto graphene oxide and coating it with an inulin folate conjugate. Paclitaxel was loaded by sonication. The hybrid was characterized by UV-Vis spectroscopy, DSC analysis and SEM microscopy. The cytotoxicity, thermoablation and anticancer activity were evaluated in vitro on MCF-7 and 16 HBE. RESULTS: In vitro tests showed that the paclitaxel-loaded hybrid improved the effectiveness of the drug especially after photothermal treatments. CONCLUSION: On the whole, while gold/graphene composite provided an excellent time-dependent photothermal effect, the loading of paclitaxel allowed a suitable chemotherapy, thus killing cancer cells both via a selective laser beam thermoablation and hyperthermia-triggered chemotherapy. PMID- 27199231 TI - Challenges in atrial fibrillation beyond stroke prevention: keeping patients out of the hospital. PMID- 27199232 TI - Metastatic spinal cord compression: diagnosis and management. PMID- 27199233 TI - Use of Bromine and Bromo-Organic Compounds in Organic Synthesis. AB - Bromination is one of the most important transformations in organic synthesis and can be carried out using bromine and many other bromo compounds. Use of molecular bromine in organic synthesis is well-known. However, due to the hazardous nature of bromine, enormous growth has been witnessed in the past several decades for the development of solid bromine carriers. This review outlines the use of bromine and different bromo-organic compounds in organic synthesis. The applications of bromine, a total of 107 bromo-organic compounds, 11 other brominating agents, and a few natural bromine sources were incorporated. The scope of these reagents for various organic transformations such as bromination, cohalogenation, oxidation, cyclization, ring-opening reactions, substitution, rearrangement, hydrolysis, catalysis, etc. has been described briefly to highlight important aspects of the bromo-organic compounds in organic synthesis. PMID- 27199234 TI - Valid statistical inference methods for a case-control study with missing data. AB - The main objective of this paper is to derive the valid sampling distribution of the observed counts in a case-control study with missing data under the assumption of missing at random by employing the conditional sampling method and the mechanism augmentation method. The proposed sampling distribution, called the case-control sampling distribution, can be used to calculate the standard errors of the maximum likelihood estimates of parameters via the Fisher information matrix and to generate independent samples for constructing small-sample bootstrap confidence intervals. Theoretical comparisons of the new case-control sampling distribution with two existing sampling distributions exhibit a large difference. Simulations are conducted to investigate the influence of the three different sampling distributions on statistical inferences. One finding is that the conclusion by the Wald test for testing independency under the two existing sampling distributions could be completely different (even contradictory) from the Wald test for testing the equality of the success probabilities in control/case groups under the proposed distribution. A real cervical cancer data set is used to illustrate the proposed statistical methods. PMID- 27199237 TI - Future of haemophilia outcome assessment: registries are key to optimized treatment. PMID- 27199235 TI - Safety and Efficacy of Thrombolysis in Cervical Artery Dissection-Related Ischemic Stroke: A Meta-Analysis of Observational Studies. AB - BACKGROUND: Although thrombolysis is considered to be the first-line treatment for ischemic stroke, there remains an ongoing controversy on the safety and efficacy of thrombolysis in cervical artery dissection (CAD). The aim of this meta-analysis was to assess observational data related to the safety and efficacy of thrombolysis in CAD-related ischemic stroke. METHODS: We performed a systematic search of the efficacy of thrombolysis treatment in CAD-related ischemic stroke with appropriate observational studies identified for the study. The meta-analysis models in Comprehensive Meta-Analysis V2 software were applied to calculate the merged rates of favorable outcome (modified Rankin Scale, mRS 0 2), excellent outcome (mRS 0-1), intracranial hemorrhage (ICH), symptomatic ICH (SICH), mortality and recurrent stroke between thrombolysis and non-thrombolysis in CAD-related stroke. The difference of outcomes and adverse events between the 2 groups was compared by analyzing the pooled OR value and chi-square test using the software SPSS. RESULTS: A total of 846 patients were identified from 10 studies (174 with thrombolysis; 672 with non-thrombolysis). The meta-analysis detected no significant statistical difference in the proportion of CAD-related stroke patients enjoying a favorable outcome at the 3 months' follow-up between the thrombolysis and non-thrombolysis groups (53.7 vs. 58.2%, OR 0.782, x03C7;2 = 0.594, p > 0.05); non-thrombolysis was slightly superior than thrombolysis in terms of excellent outcome (52.4 vs. 34.4%, OR 0.489, x03C7;2 = 9.143, p = 0.002). There was no significant difference in SICH, mortality and recurrent stroke rates between the 2 groups (all p > 0.05). ICH rate was higher in the thrombolysis group of CAD-related stroke patients compared to that in the non thrombolysis group (12.3 vs. 7.4%, OR 2.647, x03C7;2 = 4.127, p = 0.042). CONCLUSION: Thrombolysis seems to be equally safe and will achieve an efficacy similar to the efficacy of non-thrombolysis in patients with acute ischemic stroke due to CAD. It is also as effective as thrombolysis in stroke from miscellaneous causes. Therefore, CAD patients experiencing a stroke should not be denied thrombolysis therapy. However, this will need to be confirmed in large scale randomized studies, especially involving intravenous thrombolysis treatment. PMID- 27199238 TI - Granulocytic sarcoma of ovary in a post allogenic bone marrow transplant patient A diagnostic challenge to the anatomic pathologist. Case report and review of literature. PMID- 27199239 TI - ELATE: an open-source online application for analysis and visualization of elastic tensors. AB - We report on the implementation of a tool for the analysis of second-order elastic stiffness tensors, provided with both an open-source Python module and a standalone online application allowing the visualization of anisotropic mechanical properties. After describing the software features, how we compute the conventional elastic constants and how we represent them graphically, we explain our technical choices for the implementation. In particular, we focus on why a Python module is used to generate the HTML web page with embedded Javascript for dynamical plots. PMID- 27199240 TI - Seasonal Variations in the Severity of ADHD Symptoms in the Dutch General Population. AB - OBJECTIVE: This is the first study to examine self-reported seasonal differences in the severity of ADHD symptoms in adults from the general population. METHOD: Data were analyzed from N = 5,303 respondents participating in the second wave of the Netherlands Mental Health Survey and Incidence Study-2, a population-based study on mental health. ADHD symptoms were assessed using the Adult ADHD Self Report Scale Screener. As indicators of the severity of ADHD symptoms, the total ADHD symptom score and inattention and hyperactivity subscale scores were examined. RESULTS: Compared with participants who were assessed in autumn, total ADHD and inattention subscale scores were significantly higher among participants who were assessed in spring or summer; the hyperactivity subscale score was significantly higher in spring. CONCLUSION: We found seasonal variations in the severity of ADHD symptoms, which was highest in those assessed in spring and summer. Researchers should be aware of this in the diagnostic process. PMID- 27199241 TI - The GRIN2B and GRIN2A Gene Variants Are Associated With Continuous Performance Test Variables in ADHD. AB - OBJECTIVE: To examine the association between variants of N-methyl-D-aspartate (NMDA) receptor subunit-encoding genes (GRIN2A and GRIN2B) and continuous performance test (CPT) variables in ADHD and healthy controls. METHOD: In all, 253 ADHD patients and 98 controls were recruited. The diagnosis, genotype, and diagnosis-genotype interaction effects for the CPT variables were examined. RESULTS: Significant diagnosis effects were detected for all CPT variables. There were significant genotype and interaction effects on response time variability (RTV) by the GRIN2B variant. The C/C subgroup had higher RTV than the C/T + T/T subgroup in ADHD, but not in controls. There were significant genotype effects on omission errors by the GRIN2A variant. The G/G subgroup had more omission errors than the G/A + A/A subgroup in ADHD patients, but not in controls. CONCLUSION: These results suggest that the genetic variants of GRIN2B and GRIN2A confer an increased susceptibility to attentional impairment in ADHD patients. PMID- 27199242 TI - Stable Aqueous Photoelectrochemical CO2 Reduction by a Cu2 O Dark Cathode with Improved Selectivity for Carbonaceous Products. AB - Photocatalytic reduction of CO2 to produce fuels is a promising way to reduce CO2 emission and address the energy crisis. However, the H2 evolution reaction competes with CO2 photoreduction, which would lower the overall selectivity for carbonaceous products. Cu2 O has emerged as a promising material for suppressing the H2 evolution. However, it suffers from poor stability, which is commonly regarded as the result of the electron-induced reduction of Cu2 O. This paper describes a simple strategy using Cu2 O as a dark cathode and TiO2 as a photoanode to achieve stable aqueous CO2 reduction with a high Faradaic efficiency of 87.4 % and a selectivity of 92.6 % for carbonaceous products. We have shown that the photogenerated holes, instead of the electrons, primarily account for the instability of Cu2 O. Therefore, Cu2 O was used as a dark cathode to minimize the adverse effects of holes, by which an improved stability was achieved compared to the Cu2 O photocathode under illumination. Additionally, direct exposure of the Cu2 O surface to the electrolyte was identified as a critical factor for the high selectivity for carbonaceous products. PMID- 27199243 TI - Memristive Sisyphus circuit for clock signal generation. AB - Frequency generators are widely used in electronics. Here, we report the design and experimental realization of a memristive frequency generator employing a unique combination of only digital logic gates, a single-supply voltage and a realistic thresholdtype memristive device. In our circuit, the oscillator frequency and duty cycle are defined by the switching characteristics of the memristive device and external resistors. We demonstrate the circuit operation both experimentally, using a memristor emulator, and theoretically, using a model memristive device with threshold. Importantly, nanoscale realizations of memristive devices offer small-size alternatives to conventional quartz-based oscillators. In addition, the suggested approach can be used for mimicking some cyclic (Sisyphus) processes in nature, such as "dripping ants" or drops from leaky faucets. PMID- 27199244 TI - Diabetes: Human iPSC-derived beta-like cells rescue diabetic mice. PMID- 27199245 TI - Trends in clinical success rates. PMID- 27199246 TI - Neurodegenerative diseases: Laying the groundwork for remyelination. PMID- 27199247 TI - Alan Shuldiner. PMID- 27199248 TI - Infectious diseases: TIEing down vascular integrity during sepsis. PMID- 27199249 TI - Patent watch: Diagnostic patents at risk after Federal Circuit decisions. PMID- 27199250 TI - Enhancement of island size by dynamic substrate disorder in simulations of graphene growth. AB - We demonstrate a new mechanism in the early stages of sub-monolayer epitaxial island growth, using Monte Carlo simulations motivated by experimental observations on the growth of graphene on copper foil. In our model, the substrate is "dynamically rough", by which we mean (i) the interaction strength between Cu and C varies randomly from site to site, and (ii) these variable strengths themselves migrate from site to site. The dynamic roughness provides a simple representation of the near-molten state of the Cu substrate in the case of real graphene growth. Counterintuitively, the graphene island size increases when dynamic roughness is included, compared to a static and smooth substrate. We attribute this effect to destabilisation of small graphene islands by fluctuations in the substrate, allowing them to break up and join larger islands which are more stable against roughness. In the case of static roughness, when process (ii) is switched off, island growth is strongly inhibited and the scale free behaviour of island size distributions, present in the smooth-static and rough-dynamic cases, is destroyed. The effects of the dynamic substrate roughness cannot be mimicked by parameter changes in the static cases. PMID- 27199252 TI - Phyllotaxis: from patterns of organogenesis at the meristem to shoot architecture. AB - The primary architecture of the aerial part of plants is controlled by the shoot apical meristem, a specialized tissue containing a stem cell niche. The iterative generation of new aerial organs, (leaves, lateral inflorescences, and flowers) at the meristem follows regular patterns, called phyllotaxis. Phyllotaxis has long been proposed to self-organize from the combined action of growth and of inhibitory fields blocking organogenesis in the vicinity of existing organs in the meristem. In this review, we will highlight how a combination of mathematical/computational modeling and experimental biology has demonstrated that the spatiotemporal distribution of the plant hormone auxin controls both organogenesis and the establishment of inhibitory fields. We will discuss recent advances showing that auxin likely acts through a combination of biochemical and mechanical regulatory mechanisms that control not only the pattern of organogenesis in the meristem but also postmeristematic growth, to shape the shoot. WIREs Dev Biol 2016, 5:460-473. doi: 10.1002/wdev.231 For further resources related to this article, please visit the WIREs website. PMID- 27199254 TI - Inverted Gabor holography principle for tailoring arbitrary shaped three dimensional beams. AB - It is well known that by modifying the wavefront in a certain manner, the light intensity can be turned into a certain shape. However, all known light modulation techniques allow for limited light modifications only: focusing within a restricted region in space, shaping into a certain class of parametric curves along the optical axis or bending described by a quadratic-dependent deflection as in the case of Airy beams. We show a general case of classical light wavefront shaping that allows for intensity and phase redistribution into an arbitrary profile including pre-determined switching-off of the intensity. To create an arbitrary three-dimensional path of intensity, we represent the path as a sequence of closely packed individual point-like absorbers and simulate the in line hologram of the created object set; when such a hologram is contrast inverted, thus giving rise to a diffractor, it creates the pre-determined three dimensional path of intensity behind the diffractor under illumination. The crucial parameter for a smooth optical path is the sampling of the predetermined curves, which is given by the lateral and axial resolution of the optical system. We provide both, simulated and experimental results to demonstrate the power of this novel method. PMID- 27199251 TI - Clonal evolution in patients with chronic lymphocytic leukaemia developing resistance to BTK inhibition. AB - Resistance to the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib has been attributed solely to mutations in BTK and related pathway molecules. Using whole exome and deep-targeted sequencing, we dissect evolution of ibrutinib resistance in serial samples from five chronic lymphocytic leukaemia patients. In two patients, we detect BTK-C481S mutation or multiple PLCG2 mutations. The other three patients exhibit an expansion of clones harbouring del(8p) with additional driver mutations (EP300, MLL2 and EIF2A), with one patient developing trans differentiation into CD19-negative histiocytic sarcoma. Using droplet microfluidic technology and growth kinetic analyses, we demonstrate the presence of ibrutinib-resistant subclones and estimate subclone size before treatment initiation. Haploinsufficiency of TRAIL-R, a consequence of del(8p), results in TRAIL insensitivity, which may contribute to ibrutinib resistance. These findings demonstrate that the ibrutinib therapy favours selection and expansion of rare subclones already present before ibrutinib treatment, and provide insight into the heterogeneity of genetic changes associated with ibrutinib resistance. PMID- 27199255 TI - Superhydrophobic SERS chip based on a Ag coated natural taro-leaf. AB - Surface-enhanced Raman spectroscopy (SERS) substrates based on plasmonic nanostructures allow for label-free and fingerprinting molecular detection with ultrahigh sensitivity and selectivity, but their complicated and high-cost fabrication remains a challenge for practical applications and commercialization of SERS technology. Herein, we developed a facile and low-cost natural SERS substrate based on silver coated taro leaf (Taro-leaf@Ag) that exhibits ordered micro-papillae and secondary crossed nanoplates. The micro-papillae exhibited superior superhydrophobicity for analyte enrichment and the secondary crossed nanoplates provided rich SERS hot spots, which together lead to highly sensitive SERS detection with a detection limit as low as 10(-8) M. Moreover, the crossed nanoplates were uniformly distributed such that reproducible SERS measurements with a 9.7% variation over 1274 spectra was achieved. The high SERS sensitivity and reproducibility as well as the facile and low-cost fabrication make the Taro leaf@Ag a promising natural SERS substrate for future practical biochemical detection methods. PMID- 27199253 TI - Bridging the gap: heparan sulfate and Scube2 assemble Sonic hedgehog release complexes at the surface of producing cells. AB - Decision making in cellular ensembles requires the dynamic release of signaling molecules from the producing cells into the extracellular compartment. One important example of molecules that require regulated release in order to signal over several cell diameters is the Hedgehog (Hh) family, because all Hhs are synthesized as dual-lipidated proteins that firmly tether to the outer membrane leaflet of the cell that produces them. Factors for the release of the vertebrate Hh family member Sonic Hedgehog (Shh) include cell-surface sheddases that remove the lipidated terminal peptides, as well as the soluble glycoprotein Scube2 that cell-nonautonomously enhances this process. This raises the question of how soluble Scube2 is recruited to cell-bound Shh substrates to regulate their turnover. We hypothesized that heparan sulfate (HS) proteoglycans (HSPGs) on the producing cell surface may play this role. In this work, we confirm that HSPGs enrich Scube2 at the surface of Shh-producing cells and that Scube2-regulated proteolytic Shh processing and release depends on specific HS. This finding indicates that HSPGs act as cell-surface assembly and storage platforms for Shh substrates and for protein factors required for their release, making HSPGs critical decision makers for Scube2-dependent Shh signaling from the surface of producing cells. PMID- 27199257 TI - Evaluation of the Red Blood Cell Advanced Software Application on the CellaVision DM96. AB - INTRODUCTION: The CellaVision Advanced Red Blood Cell (RBC) Software Application is a new software for advanced morphological analysis of RBCs on a digital microscopy system. Upon automated precharacterization into 21 categories, the software offers the possibility of reclassification of RBCs by the operator. We aimed to define the optimal cut-off to detect morphological RBC abnormalities and to evaluate the precharacterization performance of this software. METHODS: Thirty eight blood samples of healthy donors and sixty-eight samples of hospitalized patients were analyzed. Different methodologies to define a cut-off between negativity and positivity were used. Sensitivity and specificity were calculated according to these different cut-offs using the manual microscopic method as the gold standard. Imprecision was assessed by measuring analytical within-run and between-run variability and by measuring between-observer variability. RESULTS: By optimizing the cut-off between negativity and positivity, sensitivities exceeded 80% for 'critical' RBC categories (target cells, tear drop cells, spherocytes, sickle cells, and parasites), while specificities exceeded 80% for the other RBC morphological categories. Results of within-run, between-run, and between-observer variabilities were all clinically acceptable. CONCLUSION: The CellaVision Advanced RBC Software Application is an easy-to-use software that helps to detect most RBC morphological abnormalities in a sensitive and specific way without increasing work load, provided the proper cut-offs are chosen. However, evaluation of the images by an experienced observer remains necessary. PMID- 27199258 TI - 30-day readmission after pediatric upper extremity surgery: Analysis of the NSQIP database. AB - PURPOSE: To determine the incidence and risk factors of complications, reoperations and 30-day unplanned readmission after pediatric upper extremity surgery. METHODS: Retrospective analysis of the 2013 National Surgery Quality Improvement Program pediatric database to identify procedures that met the CPT code of a primary upper extremity procedure. A univariate and multivariate analysis was performed to identify patient- and surgery-related risk factors for complications, reoperations and 30-day unplanned readmissions. RESULTS: Upper extremity pediatric surgeries have low complication (1.70%), reoperation (0.5%) and readmission rates (0.78%). Procedures requiring reoperation, inpatient procedures, and those complicated by surgical site infection were more likely to be readmitted. Patients with complex medical histories such as cardiac disease, gastrointestinal disease, pulmonary disease, or a central nervous system disorder were more likely to be readmitted. CONCLUSIONS: Pediatric upper extremity surgery is safe and associated with low complication and readmission rates. Algorithms focusing on decreasing surgical site infection and optimizing complex pediatric medical problems may limit or further decrease complication and readmission rates. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic III. PMID- 27199256 TI - Patterns of cell death in the perinatal mouse forebrain. AB - The importance of cell death in brain development has long been appreciated, but many basic questions remain, such as what initiates or terminates the cell death period. One obstacle has been the lack of quantitative data defining exactly when cell death occurs. We recently created a "cell death atlas," using the detection of activated caspase-3 (AC3) to quantify apoptosis in the postnatal mouse ventral forebrain and hypothalamus, and found that the highest rates of cell death were seen at the earliest postnatal ages in most regions. Here we have extended these analyses to prenatal ages and additional brain regions. We quantified cell death in 16 forebrain regions across nine perinatal ages from embryonic day (E) 17 to postnatal day (P) 11 and found that cell death peaks just after birth in most regions. We found greater cell death in several regions in offspring delivered vaginally on the day of parturition compared with those of the same postconception age but still in utero at the time of collection. We also found massive cell death in the oriens layer of the hippocampus on P1 and in regions surrounding the anterior crossing of the corpus callosum on E18 as well as the persistence of large numbers of cells in those regions in adult mice lacking the pro-death Bax gene. Together these findings suggest that birth may be an important trigger of neuronal cell death and identify transient cell groups that may undergo wholesale elimination perinatally. J. Comp. Neurol. 525:47-64, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27199259 TI - Functional reprogramming of human prostate cancer to promote local attraction of effector CD8(+) T cells. AB - BACKGROUND: Local infiltration of CD8(+) T cells (CTLs) in tumor lesions predicts overall clinical outcomes and the clinical benefit of cancer patients from immune checkpoint blockade. In the current study, we evaluated local production of different classes of chemokines in prostate cancer lesions, and the feasibility of their modulation to promote selective entry of CTLs into prostate tumors. METHODS: Chemokine expression in prostate cancer lesion was analyzed by TaqMan based quantitative PCR, confocal fluorescence microscopy and ELISA. For ex vivo chemokine modulation analysis, prostate tumor explants from patients undergoing primary prostate cancer resections were cultured for 24 hr, in the absence or presence of the combination of poly-I:C, IFNalpha, and celecoxib (PAC). The numbers of cells producing defined chemokines in the tissues were analyzed by confocal microscopy. Chemotaxis of effector CD8(+) T cells towards the untreated and PAC-treated tumor explant supernatants were evaluated in a standard in vitro migration assays, using 24 well trans-well plates. The number of effector cells that migrated was enumerated by flow cytometry. Pearson (r) correlation was used for analyzing correlations between chemokines and immune filtrate, while paired two tailed students t-test was used for comparison between treatment groups. RESULTS: Prostate tumors showed uniformly low levels of CTL/NK/Th1-recruiting chemokines (CCL5, CXCL9, CXCL10) but expressed high levels of chemokines implicated in the attraction of myeloid derived suppressor cells (MDSC) and regulatory T cells (Treg ): CCL2, CCL22, and CXCL12. Strong positive correlations were observed between CXCL9 and CXCL10 and local CD8 expression. Tumor expression levels of CCL2, CCL22, and CXCL12 were correlated with intratumoral expression of MDSC/Treg markers: FOXP3, CD33, and NCF2. Treatment with PAC suppressed intratumoral production of the Treg -attractant CCL22 and Treg /MDSC-attractant, CXCL12, while increasing the production of the CTL attractant, CXCL10. These changes in local chemokine production were accompanied by the reduced ability of the ex vivo-treated tumors to attract CD4(+) FOXP3(+) Treg cells, and strongly enhanced attraction of the CD8(+) Granzyme B(+) CTLs. CONCLUSIONS: Our data demonstrate that the chemokine environment in prostate cancer can be reprogrammed to selectively enhance the attraction of type-1 effector immune cells and reduce local attraction of MDSCs and Tregs . Prostate 76:1095-1105, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27199260 TI - Mapping the ecological dimensions and potential distributions of endangered relic shrubs in western Ordos biodiversity center. AB - Potential distributions of endemic relic shrubs in western Ordos were poorly mapped, which hindered our implementation of proper conservation. Here we investigated the applicability of ecological niche modeling for endangered relic shrubs to detect areas of priority for biodiversity conservation and analyze differences in ecological niche spaces used by relic shrubs. We applied ordination and niche modeling techniques to assess main environmental drivers of five endemic relic shrubs in western Ordos, namely, Ammopiptanthus mongolicus, Amygdalus mongolica, Helianthemum songaricum, Potaninia mongolica, and Tetraena mongolica. We calculated niche overlap metrics in gridded environmental spaces and compared geographical projections of ecological niches to determine similarities and differences of niches occupied by relic shrubs. All studied taxa presented different responses to environmental factors, which resulted in a unique combination of niche conditions. Precipitation availability and soil quality characteristics play important roles in the distributions of most shrubs. Each relic shrub is constrained by a unique set of environmental conditions, the distribution of one species cannot be implied by the distribution of another, highlighting the inadequacy of one-fits-all type of conservation measure. Our stacked habitat suitability maps revealed regions around Yellow River, which are highly suitable for most species, thereby providing high conservation value. PMID- 27199261 TI - Pleistocene footprints show intensive use of lake margin habitats by Homo erectus groups. AB - Reconstructing hominin paleoecology is critical for understanding our ancestors' diets, social organizations and interactions with other animals. Most paleoecological models lack fine-scale resolution due to fossil hominin scarcity and the time-averaged accumulation of faunal assemblages. Here we present data from 481 fossil tracks from northwestern Kenya, including 97 hominin footprints attributed to Homo erectus. These tracks are found in multiple sedimentary layers spanning approximately 20 thousand years. Taphonomic experiments show that each of these trackways represents minutes to no more than a few days in the lives of the individuals moving across these paleolandscapes. The geology and associated vertebrate fauna place these tracks in a deltaic setting, near a lakeshore bordered by open grasslands. Hominin footprints are disproportionately abundant in this lake margin environment, relative to hominin skeletal fossil frequency in the same deposits. Accounting for preservation bias, this abundance of hominin footprints indicates repeated use of lakeshore habitats by Homo erectus. Clusters of very large prints moving in the same direction further suggest these hominins traversed this lakeshore in multi-male groups. Such reliance on near water environments, and possibly aquatic-linked foods, may have influenced hominin foraging behavior and migratory routes across and out of Africa. PMID- 27199262 TI - Adaptation and Validation of the Spanish Version of OSA-18, a Quality of Life Questionnaire for Evaluation of Children with Sleep Apnea-Hypopnea Syndrome. AB - OBJECTIVES: To analyze the reliability and validity of the Spanish version of the OSA-18 quality of life questionnaire in children with apnea-hypopnea syndrome (SAHS). METHOD: Children with suspected SAHS were studied with polysomnography (PSG) before and after adenotonsillectomy (AA). Age, gender, clinical data, PSG, anthropometric data, and Mallampati and Brodsky scales were analyzed. OSA-18 was administered at baseline and 3-6months post AA. After translation and backtranslation by bilingual professionals, the internal consistency, reliability, construct validity, concurrent validity, predictive validity and sensitivity to change of the questionnaire was assessed. RESULTS: In total, 45 boys and 15 girls were evaluated, showing BMI 18+/-4, neck 28+/-5, Brodsky (0: 7%; <25%: 12%; 25-50%: 27%; >50 to <75%: 45%; >75%: 6%), AHI 12+/-7 pre AA. Global Cronbach alpha was 0.91. Correlations between domains were significant except for emotional aspects, although the total scores correlated with all domains (0.50 to 0.90). The factorial analysis was virtually identical to the original structure. The total scores showed good correlation for concurrent validity (0.2-0.45). With regard to predictive validity, the questionnaire adequately differentiated levels of severity according to Mallampati (ANOVA P=.002) and apnea-hypopnea index (ANOVA P=.006). Test-retest reliability was excellent, as was sensitivity to change, both in the total scores (P<.001) and in each domain (P<.001). CONCLUSIONS: The Spanish adaptation of the OSA-18 and its psychometric characteristics suggest that the Spanish version is equivalent to the original and can be used in Spanish-speaking countries. PMID- 27199263 TI - Ligand-to-ligand charge transfer in heteroleptic Ir-complexes: comprehensive investigations of its fast dynamics and mechanism. AB - To gain new insights into ligand-to-ligand charge-transfer (LLCT) dynamics, we synthesised two heteroleptic Ir(3+) complexes: (Ir(dfppy)2(tpphz)) and (Ir(dfppy)2(dpq)), where dfppy, tpphz, and dpq are 2-(4,6 difluorophenyl)pyridine, tetrapyrido[3,2-a:2',3'-c:3'',2''-h:2''',3''' j]phenazine, and 2,3-bis-(2-pyridyl)-quinoxaline, respectively. The tpphz and dpq ligands have longer pi-conjugation than dfppy. Therefore, the excited ligand centred (LC) state and the metal-to-ligand charge transfer (MLCT) state of dfppy are higher than those of tpphz and dpq. The LLCT dynamics from dfppy to tpphz (or dpq) was probed using femtoscond transient absorption (TA) spectroscopy after the selective excitation of dfppy. The TA band for the LC/MLCT state of dfppy is observed at 480 nm. Because of the LLCT process, the TA bands related to the MLCT states of tpphz and dpq ligands increased, whereas those of dfppy decreased. The time constants for the LLCT process were 17 ps for Ir(dfppy)2(tpphz) and 5 ps for Ir(dfppy)2(dpq). The MLCT emission of Ir(dfppy)2(tpphz) showed strong temperature dependence, indicating that the LLCT process has a significant energy barrier. In comparison, the temperature weakly influenced the emission of Ir(dfppy)2(dpq), and thus, its LLCT process may have a smaller barrier. The anomalous rigidochromism and photodynamic behaviours can be explained in terms of the barrier between cyclometalating and ancillary ligands. PMID- 27199265 TI - Emended description of the family Beijerinckiaceae and transfer of the genera Chelatococcus and Camelimonas to the family Chelatococcaceae fam. nov. AB - The family Beijerinckiaceae was circumscribed in 2005 to accommodate four genera of phylogenetically related alphaproteobacteria: Beijerinckia, Chelatococcus, Methylocella and Methylocapsa. Later, four additional genera, i.e. Methylovirgula, Methyloferula, Methylorosula and Camelimonas, were described and assigned to this family, which now accommodates 21 species with validly published names. Members of this family possess strikingly different lifestyles, including chemoheterotrophy, facultative methylotrophy, obligate methanotrophy and facultative methanotrophy. Levels of 16S rRNA gene sequence similarity among most of these bacteria range from 96 to 98 %, suggesting a common evolutionary origin. The genera Chelatococcus and Camelimonas, however, are not monophyletic with the other described genera based on 16S rRNA gene sequence phylogeny, and instead form a distant cluster more closely related to the Methylobacteriaceae. Physiologically these two genera also lack several properties common to the other Beijerinckiaceae. On the other hand, the genus Rhodoblastus, presently considered a member of the Bradyrhizobiaceae, affiliates with high confidence to the Beijerinckiaceae. Here, we propose to transfer the genera Chelatococcus and Camelimonas to the family Chelatococcaceae fam. nov., and present an emended description of the family Beijerinckiaceae, including the genus Rhodoblastus. PMID- 27199264 TI - Activity of aldehyde dehydrogenase in B-cell and plasma cell subsets of monoclonal gammopathy patients and healthy donors. AB - BACKGROUND: Aldehyde dehydrogenase (ALDH) is highly active in physiological stem cells as well as in tumor-initiating cells of some malignancies including multiple myeloma (MM). Finding higher activity of ALDH in some cell subsets in monoclonal gammopathies (MG) could identify potential source of myeloma initiating cells (MICs). METHODS: Bone marrow of 12 MM, 9 monoclonal gammopathy of undetermined significance (MGUS), and 10 healthy donors (HD) were analyzed by flow cytometry. ALDH activity of B-cells and plasma cells (PC) was analyzed using Aldefluor. RESULTS: Similar changes of ALDH activity were found during B-cell development in HD and MG. Decreasing of ALDH activity from immature to naive B cells was found. In postgerminal stages, the activity started to increase, and in PCs, the ALDH activity was the same as in immature B-cells. Increased ALDH activity of all PC subsets compared to naive B-cells was found in MM as well as in HD, while in MGUS, only CD19- PCs have higher ALDH activity. In HD, ALDH activity was higher in CD19+ PCs compared with MG. CONCLUSIONS: Our results indicate that changes of ALDH activity are the natural phenomenon in B-cell development; thus, high ALDH activity as a single marker is not appropriate for MICs identification. PMID- 27199266 TI - Nano-Enabled Approaches for Stem Cell-Based Cardiac Tissue Engineering. AB - Cardiac diseases are the most prevalent causes of mortality in the world, putting a major economic burden on global healthcare system. Tissue engineering strategies aim at developing efficient therapeutic approaches to overcome the current challenges in prolonging patients survival upon cardiac diseases. The integration of advanced biomaterials and stem cells has offered enormous promises for regeneration of damaged myocardium. Natural or synthetic biomaterials have been extensively used to deliver cells or bioactive molecules to the site of injury in heart. Additionally, nano-enabled approaches (e.g., nanomaterials, nanofeatured surfaces) have been instrumental in developing suitable scaffolding biomaterials and regulating stem cells microenvironment to achieve functional therapeutic outcomes. This review article explores tissue engineering strategies, which have emphasized on the use of nano-enabled approaches in combination with stem cells for regeneration and repair of injured myocardium upon myocardial infarction (MI). Primarily a wide range of biomaterials, along with different types of stem cells, which have utilized in cardiac tissue engineering will be presented. Then integration of nanomaterials and surface nanotopographies with biomaterials and stem cells for myocardial regeneration will be presented. The advantages and challenges of these approaches will be reviewed and future perspective will be discussed. PMID- 27199268 TI - Charting the Future of SPN: The SPN Strategic Plan. PMID- 27199267 TI - Membrane Topology and Structural Insights into the Peptide Pheromone Receptor ComD, A Quorum-Sensing Histidine Protein Kinase of Streptococcus mutans. AB - Quorum sensing activation by signal pheromone (CSP) in Streptococcus mutans depends on the membrane-associated receptor ComD, which senses the signal and triggers the signaling cascade for bacteriocin production and other cell density dependent activities. However, the mechanism of the signal recognition via the ComD receptor in this species is nearly unexplored. Here, we show that the membrane domain of the ComD protein forms six transmembrane segments with three extracellular loops, loopA, loopB and loopC. By structural and functional analyses of these extracellular loops, we demonstrate that both loopC and loopB are required for CSP recognition, while loopA plays little role in CSP detection. A deletion or substitution mutation of four residues NVIP in loopC abolishes CSP recognition for quorum sensing activities. We conclude that both loopC and loopB are required for forming the receptor and residues NVIP of loopC are essential for CSP recognition and quorum sensing activation in S. mutans. PMID- 27199269 TI - Olanzapine for the prophylaxis and rescue of chemotherapy-induced nausea and vomiting (CINV): a retrospective study. AB - BACKGROUND: While the efficacy of olanzapine in the prophylaxis of chemotherapy induced nausea and vomiting (CINV) has been documented, the literature on the use of olanzapine as a rescue medication for breakthrough CINV has been scarce. The following study retrospectively evaluated the safety and efficacy of olanzapine for the treatment of breakthrough CINV. The efficacy and safety of olanzapine in the prophylactic setting was also examined in a smaller cohort. METHODS: Electronic medical records of adult patients aged >17 years receiving a prescription for olanzapine from the Odette Cancer Centre Pharmacy at Sunnybrook Hospital between January 2013 and June 2015 were reviewed retrospectively. Inclusion criteria required receiving one or more doses of olanzapine for the rescue or prophylaxis of CINV and documentation of the outcome. RESULTS: A total of 154 patients and 193 treatment cycles were included in the breakthrough setting, while a total of 16 patients and 20 treatment cycles were included in the prophylaxis setting. In the breakthrough setting, 88% of cases experienced improved nausea, while 21% of cases reported improved vomiting. In the prophylactic setting, 100% of cases experienced improved nausea, while 65% achieved improved vomiting. A total of 43% of cases in the breakthrough setting and 65% of cases in the prophylactic setting experienced sedation. CONCLUSIONS: Olanzapine is effective in improving CINV in both the prophylactic and breakthrough settings. The safety, efficacy, and appropriate dosage of olanzapine for the rescue of breakthrough CINV should be prospectively evaluated in a randomized controlled trial (RCT). PMID- 27199270 TI - Quality of life with Brain Symptom and Impact Questionnaire in patients with brain metastases. AB - BACKGROUND: To examine the baseline characteristics of patients who underwent different treatments for brain metastases. METHODS: Allocated into group A [whole brain radiation therapy (WBRT) alone], or group B [stereotactic radiosurgery (SRS) or neurosurgery with or without WBRT], brain metastases patients with assigned treatment completed the Brain Symptom and Impact Questionnaire (BASIQ). Items of BASIQ were arranged as a symptom score or function score. RESULTS: Lung, breast, melanoma and renal cancer were the most prevalent primary cancer site among the study population, with 91 (53%), 25 (15%), 17 (10%) and 15 (9%) patients, respectively. Baseline BASIQ results were obtained before patients were treated with WBRT, neurosurgery, or SRS. Seventy-six (44%) and 96 patients (56%) were grouped to A and B, respectively. Group A reported lower quality of life (QOL) in all function scores (P<0.0001) and all symptom scores (P values from <0.0001 to 0.005) with the exception of energy (P=0.1). CONCLUSIONS: Baseline QOL in patients assigned WBRT alone was statistically worse as compared to patients assigned SRS, neurosurgery with or without WBRT. PMID- 27199271 TI - Child's symptom burden and depressive symptoms among caregivers of children with cancers: an argument for early integration of pediatric palliative care. AB - BACKGROUND: Childhood cancers evoke various emotional reactions in caregivers which can impair their well-being and roles. Little is known about caregiving and which cancer-associated factors are related to caregiver's depression in resource restricted settings. We sought to investigate if child's symptom burden is related to depressive symptoms in caregivers. METHODS: Seventy-two caregivers and children with cancers were administered questionnaires to elicit socio demographic and disease-related data. Subsequently, the child's symptoms were profiled with Memorial Symptom Assessment Scale (MSAS 7-12); while screening for depressive symptoms in caregivers was done using the Center for Epidemiologic Studies Depression Scale-Revised (CES-DR). RESULTS: All the caregivers were parents, and largely mothers (83.7%). The mean ages of caregivers and children were 39+/-2 and 10+/-2 years respectively. Majority of caregivers (90.3%) were either ignorant or attributed spiritual causation to the cancers. The common symptoms with prevalence >50% in the children included pain, nausea, worry, and lack of energy (LE); symptoms' prevalence ranged from LE (68%) to itching (32%). Approximately, one-third each of the children reported hair and weight loss which were considered 'unusual' in the design of MSAS 7-12. The symptoms showed variability in distress, frequency and intensity. In particular, pain, lack of appetite (LA) and feeling sad (FS) were reported as most burdensome in >50% of the children. More than one-third of caregivers (38.2%) screened positive for significant depressive symptoms. The global symptom burden (r=0.58) and individual symptom correlated positively with depressive symptoms in caregivers (P<0.05). CONCLUSIONS: Our findings suggest the need for improved awareness creation on childhood cancers to obviate late presentations and poor access to care. Again, early integration of pediatric palliative care in childhood cancer care to ensure symptom management as well as its extended benefits on caregivers' wellbeing is desirable. The pattern of certain "unusual" symptoms in children with cancer in our work suggests the need to put into consideration 'novel' symptoms which were not captured in existing instruments. Future research on supportive care in pediatric cancers is indicated. PMID- 27199272 TI - Solitary brain metastasis from prostate cancer: a case report. AB - Brain metastases arising from prostate cancer are exceedingly rare and typically occur late in the course of the disease. Most patients have widespread metastatic disease before developing brain metastases from prostate cancer. We report the case of a 67-year-old male with prostate cancer presenting with an isolated symptomatic brain metastasis. Aggressive treatment of the metastatic site included tumor resection and adjuvant stereotactic radiation treatment (RT) to the surgical bed, resulting in a favorable outcome. PMID- 27199273 TI - Translation Initiation is Controlled by RNA Folding Kinetics via a Ribosome Drafting Mechanism. AB - RNA folding plays an important role in controlling protein synthesis as well as other cellular processes. Existing models have focused on how RNA folding energetics control translation initiation rate under equilibrium conditions but have largely ignored the effects of nonequilibrium RNA folding. We introduce a new mechanism, called "ribosome drafting", that explains how a mRNA's folding kinetics and the ribosome's binding rate collectively control its translation initiation rate. During cycles of translation, ribosome drafting emerges whenever successive ribosomes bind to a mRNA faster than the mRNA can refold, maintaining it in a nonequilibrium state with an acceleration of protein synthesis. Using computational design, time-correlated single photon counting, and expression measurements, we demonstrate that slow-folding and fast-folding RNA structures with equivalent folding energetics can vary protein synthesis rates by 1000-fold. We determine the necessary conditions for ribosome drafting by characterizing mRNAs with rationally designed ribosome binding rates, folding kinetics, and folding energetics, confirming the predictions of a nonequilibrium Markov model of translation. Our results have widespread implications, illustrating how competitive folding and assembly kinetics can shape the gene expression machinery's sequence-structure-function relationship inside cells. PMID- 27199275 TI - The weekend effect-how strong is the evidence? PMID- 27199274 TI - Care of patients using progestogen-only injectables. PMID- 27199277 TI - An electrochemical platform for localized pH control on demand. AB - Solution pH is a powerful tool for regulating many kinds of chemical activity, but is generally treated as a static property defined by a pre-selected buffer. Introducing dynamic control of pH in space, time, and magnitude can enable richer and more efficient chemistries, but is not feasible with traditional methods of titration or buffer exchange. Recent reports have featured electrochemical strategies for modifying bulk pH in constrained volumes, but only demonstrate switching between two preset values and omit spatial control entirely. Here, we use a combination of solution-borne quinones and galvanostatic excitation to enable quantitative control of pH environments that are highly localized to an electrode surface. We demonstrate highly reproducible acidification and alkalinization with up to 0.1 pH s(-1) (+/-0.002 pH s(-1)) rate of change across the dynamic range of our pH sensor (pH 4.5 to 7.5) in buffered solutions. Using dynamic current control, we generate and sustain 3 distinct pH microenvironments simultaneously to within +/-0.04 pH for 13 minutes in a single solution, and we leverage these microenvironments to demonstrate spatially-resolved, pH-driven control of enzymatic activity. In addition to straightforward applications of spatio-temporal pH control (e.g. efficiently studying pH-dependencies of chemical interactions), the technique opens completely new avenues for implementing complex systems through dynamic control of enzyme activation, protein binding affinity, chemical reactivity, chemical release, molecular self-assembly, and many more pH-controlled processes. PMID- 27199276 TI - Interfraction Anatomical Variability Can Lead to Significantly Increased Rectal Dose for Patients Undergoing Stereotactic Body Radiotherapy for Prostate Cancer. AB - Stereotactic body radiotherapy for prostate cancer is rapidly growing in popularity. Stereotactic body radiotherapy plans mimic those of high-dose rate brachytherapy, with tight margins and inhomogeneous dose distributions. The impact of interfraction anatomical changes on the dose received by organs at risk under these conditions has not been well documented. To estimate anatomical variation during stereotactic body radiotherapy, 10 patients were identified who received a prostate boost using robotic stereotactic body radiotherapy after completing 25 fractions of pelvic radiotherapy with daily megavoltage computed tomography. Rectal and bladder volumes were delineated on each megavoltage computed tomography, and the stereotactic body radiotherapy boost plan was registered to each megavoltage computed tomography image using a point-based rigid registration with 3 fiducial markers placed in the prostate. The volume of rectum and bladder receiving 75% of the prescription dose (V75%) was measured for each megavoltage computed tomography. The rectal V75% from the daily megavoltage computed tomographies was significantly greater than the planned V75% (median increase of 0.93 cm3, P < .001), whereas the bladder V75% on megavoltage computed tomography was not significantly changed (median decrease of -0.12 cm3, P = .57). Although daily prostate rotation was significantly correlated with bladder V75% (Spearman rho = .21, P = .023), there was no association between rotation and rectal V75% or between prostate deformation and either rectal or bladder V75%. Planning organ-at-risk volume-based replanning techniques using either a 6-mm isotropic expansion of the plan rectal contour or a 1-cm expansion from the planning target volume in the superior and posterior directions demonstrated significantly improved rectal V75% on daily megavoltage computed tomographies compared to the original stereotactic body radiotherapy plan, without compromising plan quality. Thus, despite tight margins and full translational and rotational corrections provided by robotic stereotactic body radiotherapy, we find that interfraction anatomical variations can lead to a substantial increase in delivered rectal doses during prostate stereotactic body radiotherapy. A planning organ-at-risk volume-based approach to treatment planning may help mitigate the impact of daily organ motion and reduce the risk of rectal toxicity. PMID- 27199278 TI - Concurrent oocyte retrieval and hysteroscopy: a novel approach in assisted reproduction freeze-all cycles. AB - In this matched-controlled study (n = 300), the effect of hysteroscopic surgery performed concurrently with oocyte retrieval on the reproductive outcomes of intracytoplasmic sperm injection (ICSI) freeze-all cycles was investigated in patients screened for intrauterine anomalies. Conventionally, hysterscopic surgery is performed in a different cycle from IVF, delaying treatment completion and increasing patient anxiety. One hundred and fifty patients who had hysteroscopic surgery concurrently with oocyte retrieval (hysteroscopy group) in ICSI freeze-all cycles were matched according to age and oocyte number with 150 ICSI freeze-all cycles, in which the patients required no hysteroscopy (control group). In the hysteroscopy group, hysteroscopy was performed for diagnostic (n = 5) and therapeutic (n = 145) purposes. Blastocyst culture and Cryotop vitrification was performed in both groups. Frozen embryo transfer (FET) was successfully performed in the hysteroscopy group from 35 days after oocyte retrieval. No significant differences were observed for implantation, pregnancy, clinical pregnancy and early pregnancy loss rates in the hysteroscopy and control groups (48.9%, 72.0%, 61.3% and 14.8% versus 48.3%, 75.3%, 64.7% and 14.3%, respectively). Performing hysteroscopic surgery concurrently with oocyte retrieval in a segmented-IVF programme has no negative impact on reproductive outcomes, increases efficiency, and provides patients with low-risk treatment. PMID- 27199279 TI - Children's science learning: A core skills approach. AB - BACKGROUND: Research has identified the core skills that predict success during primary school in reading and arithmetic, and this knowledge increasingly informs teaching. However, there has been no comparable work that pinpoints the core skills that underlie success in science. AIMS AND METHOD: The present paper attempts to redress this by examining candidate skills and considering what is known about the way in which they emerge, how they relate to each other and to other abilities, how they change with age, and how their growth may vary between topic areas. RESULTS: There is growing evidence that early-emerging tacit awareness of causal associations is initially separated from language-based causal knowledge, which is acquired in part from everyday conversation and shows inaccuracies not evident in tacit knowledge. Mapping of descriptive and explanatory language onto causal awareness appears therefore to be a key development, which promotes unified conceptual and procedural understanding. CONCLUSIONS: This account suggests that the core components of initial science learning are (1) accurate observation, (2) the ability to extract and reason explicitly about causal connections, and (3) knowledge of mechanisms that explain these connections. Observational ability is educationally inaccessible until integrated with verbal description and explanation, for instance, via collaborative group work tasks that require explicit reasoning with respect to joint observations. Descriptive ability and explanatory ability are further promoted by managed exposure to scientific vocabulary and use of scientific language. Scientific reasoning and hypothesis testing are later acquisitions that depend on this integration of systems and improved executive control. PMID- 27199280 TI - Marinomonas gallaica sp. nov. and Marinomonas atlantica sp. nov., isolated from reared clams (Ruditapes decussatus). AB - Three Gram-negative bacterial strains (Cmf 17.2T, Rd 20.33 and Cmf 18.22T) isolated from reared clams in Galicia were subjected to a taxonomic study, based on genetic and phenotypic characterization. Analysis of the 16S rRNA gene allowed the identification of the strains as members of the genus Marinomonas, sharing the highest similarity with Marinomonas aquimarina CECT 5080T (97.8 %-98.5 % 16S rRNA gene sequence similarity). Phylogenetic analysis of the sequences showed that the three isolates formed two different groups distantly related to their closest relative, M. aquimarina. DNA-DNA hybridizations were performed to confirm the taxonomic position and the results were below the recommended threshold for species delimitation, specifically 44.5 % (Cmf 17.2T with M. aquimarina CECT 5080T) and 55 % (Cmf 18.22Twith M. aquimarina CECT 5080T). Furthermore, the average nucleotide identity (ANIb, ANIm and OrthoANI) and in silico estimated DNA DNA reassociation values among Cmf 17.2T, Cmf 18.22T and M. aquimarina CECT 5080T were in all cases below the respective threshold for species differentiation. The estimated G+C content of the genomic DNA was found to be 45.3 % (Cmf 17.2T) and 44.6 % (Cmf 18.22T). The principal fatty acids of the strains were found to be summed feature 3 (C16 : 1 omega7c/C16 : 1omega6c), summed feature 8 (C18 : 1omega7c/C18 : 1omega6c), C16 : 0, C12 : 0 and C10 : 0 3-OH. The results obtained on the characterization of the clam isolates indicate that they represent two novel species of the genus Marinomonas, for which the names Marinomonas gallaica sp. nov. (type strain Cmf 17.2T=CECT 9049T=LMG 29243T) and Marinomonas atlantica sp. nov. (type strain Cmf 18.22T=CECT 9050T=LMG 29244T) are proposed. PMID- 27199281 TI - How can mental health and faith-based practitioners work together? A case study of collaborative mental health in Gujarat, India. AB - Despite the knowledge that people with mental illness often seek care from multiple healing systems, there is limited collaboration between these systems. Greater collaboration with existing community resources could narrow the treatment gap and reduce fragmentation by encouraging more integrated care. This paper explores the origins, use, and outcomes of a collaborative programme between faith-based and allopathic mental health practitioners in India. We conducted 16 interviews with key stakeholders and examined demographic and clinical characteristics of the user population. Consistent with previous research, we found that collaboration is challenging and requires trust, rapport building, and open dialogue. The collaboration reached a sizeable population, was reviewed favourably by key stakeholders-particularly on health improvement and livelihood restoration-and perhaps most importantly, views the client holistically, allowing for both belief systems to play a shared role in care and recovery. Results support the idea that, despite differing practices, collaboration between faith-based and allopathic mental health practitioners can be achieved and can benefit clients with otherwise limited access to mental health care. PMID- 27199282 TI - Potential Involvement of Draxin in the Axonal Projection of Cranial Nerves, Especially Cranial Nerve X, in the Chick Hindbrain. AB - The appropriate projection of axons within the nervous system is a crucial component of the establishment of neural circuitry. Draxin is a repulsive axon guidance protein. Draxin has important functions in the guidance of three commissures in the central nervous system and in the migration of neural crest cells and dI3 interneurons in the chick spinal cord. Here, we report that the distribution of the draxin protein and the location of 23C10-positive areas have a strong temporal and spatial correlation. The overexpression of draxin, especially transmembrane draxin, caused 23C10-positive axon bundles to misproject in the dorsal hindbrain. In addition, the overexpression of transmembrane draxin caused abnormal formation of the ganglion crest of the IX and X cranial nerves, misprojection of some anti-human natural killer-1 (HNK-1)-stained structures in the dorsal roof of the hindbrain, and a simultaneous reduction in the efferent nerves of some motoneuron axons inside the hindbrain. Our data reveal that draxin might be involved in the fascicular projection of cranial nerves in the hindbrain. PMID- 27199284 TI - Correction to Use of a Lipid-Coated Mesoporous Silica Nanoparticle Platform for Synergistic Gemcitabine and Paclitaxel Delivery to Human Pancreatic Cancer in Mice. PMID- 27199283 TI - MicroRNA-30 inhibits neointimal hyperplasia by targeting Ca(2+)/calmodulin dependent protein kinase IIdelta (CaMKIIdelta). AB - The multifunctional Ca(2+)/calmodulin-dependent protein kinase II delta-isoform (CaMKIIdelta) promotes vascular smooth muscle (VSM) proliferation, migration, and injury-induced vascular wall neointima formation. The objective of this study was to test if microRNA-30 (miR-30) family members are endogenous regulators of CaMKIIdelta expression following vascular injury and whether ectopic expression of miR-30 can inhibit CaMKIIdelta-dependent VSM cell function and neointimal VSM hyperplasia induced by vascular injury. The CaMKIIdelta 3'UTR contains a consensus miR-30 binding sequence that is highly conserved across species. A significant decrease in miR-30 family members and increase in CaMKIIdelta2 protein expression, with no change in CaMKIIdelta mRNA expression, was observed in medial layers of VSM 7 days post-injury. In vitro, overexpression of miR-30c or miR-30e inhibited CaMKIIdelta2 protein expression by ~50% in cultured rat aortic VSM cells, and inhibited VSM cell proliferation and migration. In vivo, lenti-viral delivery of miR-30c into injured rat carotid arteries prevented the injury-induced increase in CaMKIIdelta2. Furthermore, neointima formation was dramatically inhibited by lenti-viral delivery of miR-30c in the injured medial smooth muscle. These studies define a novel mechanism for regulating CaMKIIdelta expression in VSM and provide a new potential therapeutic strategy to reduce progression of vascular proliferative diseases, including atherosclerosis and restenosis. PMID- 27199285 TI - Selenium-Doped Black Phosphorus for High-Responsivity 2D Photodetectors. AB - Se-doped black phosphorus (BP) crystal, in centimeter scale, is synthesized by a scalable gas-phase growth method under mild conditions. The Se-doped BP exhibits high quality with excellent electrical properties. The Se dope induces over 20 fold enhancement of responsivity (R) for BP-based 2D photodetectors, resulting in a high R and external quantum efficiency of 15.33 A W-1 and 2993%, respectively. PMID- 27199286 TI - Prevention of antipsychotic-induced hyperglycaemia by vitamin D: a data mining prediction followed by experimental exploration of the molecular mechanism. AB - Atypical antipsychotics are associated with an increased risk of hyperglycaemia, thus limiting their clinical use. This study focused on finding the molecular mechanism underlying antipsychotic-induced hyperglycaemia. First, we searched for drug combinations in the FDA Adverse Event Reporting System (FAERS) database wherein a coexisting drug reduced the hyperglycaemia risk of atypical antipsychotics, and found that a combination with vitamin D analogues significantly decreased the occurrence of quetiapine-induced adverse events relating diabetes mellitus in FAERS. Experimental validation using mice revealed that quetiapine acutely caused insulin resistance, which was mitigated by dietary supplementation with cholecalciferol. Further database analysis of the relevant signalling pathway and gene expression predicted quetiapine-induced downregulation of Pik3r1, a critical gene acting downstream of insulin receptor. Focusing on the phosphatidylinositol 3-kinase (PI3K) signalling pathway, we found that the reduced expression of Pik3r1 mRNA was reversed by cholecalciferol supplementation in skeletal muscle, and that insulin-stimulated glucose uptake into C2C12 myotube was inhibited in the presence of quetiapine, which was reversed by concomitant calcitriol in a PI3K-dependent manner. Taken together, these results suggest that vitamin D coadministration prevents antipsychotic induced hyperglycaemia and insulin resistance by upregulation of PI3K function. PMID- 27199287 TI - Progress in the care of common inherited atherogenic disorders of apolipoprotein B metabolism. AB - Familial hypercholesterolaemia, familial combined hyperlipidaemia (FCH) and elevated lipoprotein(a) are common, inherited disorders of apolipoprotein B metabolism that markedly accelerate the onset of atherosclerotic cardiovascular disease (ASCVD). These disorders are frequently encountered in clinical lipidology and need to be accurately identified and treated in both index patients and their family members, to prevent the development of premature ASCVD. The optimal screening strategies depend on the patterns of heritability for each condition. Established therapies are widely used along with lifestyle interventions to regulate levels of circulating lipoproteins. New therapeutic strategies are becoming available, and could supplement traditional approaches in the most severe cases, but their long-term cost-effectiveness and safety have yet to be confirmed. We review contemporary developments in the understanding, detection and care of these highly atherogenic disorders of apolipoprotein B metabolism. PMID- 27199288 TI - Diabetes: Hypoglycaemia risk with dual use of DPP-4 inhibitors and sulphonylureas. PMID- 27199289 TI - Obesity: Consequences of AMPK activation. PMID- 27199290 TI - Control of puberty onset and fertility by gonadotropin-releasing hormone neurons. AB - The gonadotropin-releasing hormone (GnRH) neuronal network generates pulse and surge modes of gonadotropin secretion critical for puberty and fertility. The arcuate nucleus kisspeptin neurons that innervate the projections of GnRH neurons in and around their neurosecretory zone are key components of the pulse generator in all mammals. By contrast, kisspeptin neurons located in the preoptic area project to GnRH neuron cell bodies and proximal dendrites and are involved in surge generation in female rodents (and possibly other species). The hypothalamic pituitary-gonadal axis develops embryonically but, apart from short periods of activation immediately after birth, remains suppressed through a combination of gonadal and non-gonadal mechanisms. At puberty onset, the pulse generator reactivates, probably owing to progressive stimulatory influences on GnRH neurons from glial and neurotransmitter signalling, and the re-emergence of stimulatory arcuate kisspeptin input. In females, the development of pulsatile gonadotropin secretion enables final maturation of the surge generator that ultimately triggers the first ovulation. Representation of the GnRH neuronal network as a series of interlocking functional modules could help conceptualization of its functioning in different species. Insights into pulse and surge generation are expected to aid development of therapeutic strategies ameliorating pubertal disorders and infertility in the clinic. PMID- 27199292 TI - Thyroid gland: Genetic insight into antithyroid drug-induced agranulocytosis in a European population. PMID- 27199293 TI - Pituitary gland: Sex difference in comorbidity burden associated with nonfunctioning pituitary adenomas. PMID- 27199294 TI - Epidemiology: The diabetes mellitus tsunami: worse than the 'Spanish flu' pandemic? PMID- 27199295 TI - What consumers don't know about genetically modified food, and how that affects beliefs. AB - In the debates surrounding biotechnology and genetically modified (GM) food, data from consumer polls are often presented as evidence for precaution and labeling. But how much do consumers actually know about the issue? New data collected from a nationwide U.S. survey reveal low levels of knowledge and numerous misperceptions about GM food. Nearly equal numbers of consumers prefer mandatory labeling of foods containing DNA as do those preferring mandatory labeling of GM foods. When given the option, the majority of consumers prefer that decisions about GM food be taken out of their hands and be made by experts. After answering a list of questions testing objective knowledge of GM food, subjective, self reported knowledge declines somewhat, and beliefs about GM food safety increase slightly. Results suggest that consumers think they know more than they actually do about GM food, and queries about GM facts cause respondents to reassess how much they know. The findings question the usefulness of results from opinion polls as a motivation for creating public policy surrounding GM food.-McFadden, B. R., Lusk, J. L. What consumers don't know about genetically modified food, and how that affects beliefs. PMID- 27199291 TI - Hypothalamic AMPK: a canonical regulator of whole-body energy balance. AB - AMP-activated protein kinase (AMPK) has a major role in the modulation of energy balance. AMPK is activated in conditions of low energy, increasing energy production and reducing energy consumption. The AMPK pathway is a canonical route regulating energy homeostasis by integrating peripheral signals, such as hormones and metabolites, with neuronal networks. Current evidence has implicated AMPK in the hypothalamus and hindbrain with feeding, brown adipose tissue thermogenesis and browning of white adipose tissue, through modulation of the sympathetic nervous system, as well as glucose homeostasis. Interestingly, several potential antiobesity and/or antidiabetic agents, some of which are currently in clinical use such as metformin and liraglutide, exert some of their actions by acting on AMPK. Furthermore, the orexigenic and weight-gain effects of commonly used antipsychotic drugs are also mediated by hypothalamic AMPK. Overall, this evidence suggests that hypothalamic AMPK signalling is an interesting target for drug development, but is this approach feasible? In this Review we discuss the current understanding of hypothalamic AMPK and its role in the central regulation of energy balance and metabolism. PMID- 27199296 TI - Dendritic cells primed with a chimeric plasmid containing HIV-1-gag associated with lysosomal-associated protein-1 (LAMP/gag) is a potential therapeutic vaccine against HIV. AB - The decline in number and function of T cells is a hallmark of HIV infection, and preservation or restoration of HIV-specific cellular immune response is a major goal of AIDS treatment. Dendritic cells (DCs) play a key role in the initiation and maintenance of the immune response, and their use as a vaccine vehicle is a promising strategy for enhancing vaccine efficacy. We evaluated the potential of DC-mediated immunization with a DNA vaccine consisting of HIV-1-p55gag (gag, group-specific antigen) associated to lysosomal associated protein (LAMP) sequence (LAMP/gag vaccine). Immunization of mice with mouse DCs transfected with LAMP/gag (Lg-mDCs) stimulated more potent B- and T-cell responses than naked DNA or DCs pulsed with inactivated HIV. Anti-Gag antibody levels were sustained for at least 3 mo after immunization, and recall T-cell responses were also strongly detected at this time point. Human DCs transfected with LAMP/gag (Lg-hDCs) were also activated and able to stimulate greater T-cell response than native gag transfected DCs. Coculture between Lg-hDCs and T lymphocytes obtained from patients with HIV resulted in upregulation of CD38, CD69, HLA-DR, and granzyme B by CD4(+) and CD8(+) T cells, and increased IFN-gamma and TNF-alpha production. These results indicate that the use of LAMP/gag-DC may be an efficient strategy for enhancing immune function in patients with HIV.-Lucas, C. G. D. O., Matassoli, F. L., Pecanha, L. M. T., Santillo, B. T., Oliveira, L. M. D. S., Oshiro, T. M., Marques, E. T. D. A., Jr., Oxenius, A., de Arruda, L. B. Dendritic cells primed with a chimeric plasmid containing HIV-1-gag associated with lysosomal-associated protein-1 (LAMP/gag) is a potential therapeutic vaccine against HIV. PMID- 27199297 TI - Proposal for a transmon-based quantum router. AB - We propose an implementation of a quantum router for microwave photons in a superconducting qubit architecture consisting of a transmon qubit, SQUIDs and a nonlinear capacitor. We model and analyze the dynamics of operation of the quantum switch using quantum Langevin equations in a scattering approach and compute the photon reflection and transmission probabilities. For parameters corresponding to up-to-date experimental devices we predict successful operation of the router with probabilities above 94%. PMID- 27199298 TI - Preserving medical correctness, readability and consistency in de-identified health records. AB - A health record database contains structured data fields that identify the patient, such as patient ID, patient name, e-mail and phone number. These data are fairly easy to de-identify, that is, replace with other identifiers. However, these data also occur in fields with doctors' free-text notes written in an abbreviated style that cannot be analyzed grammatically. If we replace a word that looks like a name, but isn't, we degrade readability and medical correctness. If we fail to replace it when we should, we degrade confidentiality. We de-identified an existing Danish electronic health record database, ending up with 323,122 patient health records. We had to invent many methods for de identifying potential identifiers in the free-text notes. The de-identified health records should be used with caution for statistical purposes because we removed health records that were so special that they couldn't be de-identified. Furthermore, we distorted geography by replacing zip codes with random zip codes. PMID- 27199299 TI - Evaluation of Ki-67 antigen expression in the vaginal epithelium of castrated female rats treated with raloxifene and tamoxifen: a comparative study. AB - OBJECTIVE: The aim of this study was to evaluate the effects of raloxifene and tamoxifen on Ki-67 antigen expression in the vaginal epithelium of castrated rats. MATERIAL AND METHODS: Thirty-nine virgin, adult, castrated female Wistar Hannover rats were randomly divided into three groups: Group I (control, n = 13), Group II (raloxifene, n = 13) and Group III (tamoxifen, n = 13). After confirmation of their hypoestrogenic state, the rats were given 0.5 ml of propylene glycol (vehicle), 750 MUg of raloxifene or 250 MUg of tamoxifen, respectively, by gavage, for 30 days. On the 31st day, the rats were euthanized and their vaginas removed and fixed in 10% buffered formalin for of Ki-67 immunohistochemical evaluation. Data were analyzed using Levene's test and Tukey's method (p < 0.05). RESULTS: Mean Ki-67 expression in groups I, II and III was 27 +/- 2.6, 32.3 +/- 1.9 and 43.7 +/- 3.5, respectively. In Group III (tamoxifen), there was a greater proportion of stained cells compared to Groups I and II (p < 0.0003), with no statistically significant difference between Groups I and II (p = 0.3626). CONCLUSIONS: The present results show that tamoxifen significantly increased cell proliferation in the vaginal epithelium of the castrated rats and no difference between the raloxifene and control groups. PMID- 27199300 TI - Predicting global invasion risks: a management tool to prevent future introductions. AB - Predicting regions at risk from introductions of non-native species and the subsequent invasions is a fundamental aspect of horizon scanning activities that enable the development of more effective preventative actions and planning of management measures. The Asian cyprinid fish topmouth gudgeon Pseudorasbora parva has proved highly invasive across Europe since its introduction in the 1960s. In addition to direct negative impacts on native fish populations, P. parva has potential for further damage through transmission of an emergent infectious disease, known to cause mortality in other species. To quantify its invasion risk, in regions where it has yet to be introduced, we trained 900 ecological niche models and constructed an Ensemble Model predicting suitability, then integrated a proxy for introduction likelihood. This revealed high potential for P. parva to invade regions well beyond its current invasive range. These included areas in all modelled continents, with several hotspots of climatic suitability and risk of introduction. We believe that these methods are easily adapted for a variety of other invasive species and that such risk maps could be used by policy makers and managers in hotspots to formulate increased surveillance and early warning systems that aim to prevent introductions and subsequent invasions. PMID- 27199301 TI - Microfluidic paper-based biomolecule preconcentrator based on ion concentration polarization. AB - Microfluidic paper-based analytical devices (MUPADs) for molecular detection have great potential in the field of point-of-care diagnostics. Currently, a critical problem being faced by MUPADs is improving their detection sensitivity. Various preconcentration processes have been developed, but they still have complicated structures and fabrication processes to integrate into MUPADs. To address this issue, we have developed a novel paper-based preconcentrator utilizing ion concentration polarization (ICP) with minimal addition on lateral-flow paper. The cation selective membrane (i.e., Nafion) is patterned on adhesive tape, and this tape is then attached to paper-based channels. When an electric field is applied across the Nafion, ICP is initiated to preconcentrate the biomolecules in the paper channel. Departing from previous paper-based preconcentrators, we maintain steady lateral fluid flow with the separated Nafion layer; as a result, fluorescent dyes and proteins (FITC-albumin and bovine serum albumin) are continuously delivered to the preconcentration zone, achieving high preconcentration performance up to 1000-fold. In addition, we demonstrate that the Nafion-patterned tape can be integrated with various geometries (multiplexed preconcentrator) and platforms (string and polymer microfluidic channel). This work would facilitate integration of various ICP devices, including preconcentrators, pH/concentration modulators, and micro mixers, with steady lateral flows in paper-based platforms. PMID- 27199302 TI - Tunable coating of gold nanostars: tailoring robust SERS labels for cell imaging. AB - Surface modification of noble metal nanoparticles with mixed molecular monolayers is one of the most powerful tools in nanotechnology, and is used to impart and tune new complex surface properties. In imaging techniques based on surface enhanced Raman spectroscopy (SERS), precise and controllable surface modifications are needed to carefully design reproducible, robust and adjustable SERS nanoprobes. We report here the attainment of SERS labels based on gold nanostars (GNSs) coated with a mixed monolayer composed of a poly ethylene glycol (PEG) thiol (neutral or negatively charged) that ensure stability in biological environments, and of a signalling unit 7-Mercapto-4-methylcoumarin as a Raman reporter molecule. The composition of the coating mixture is precisely controlled using an original method, allowing the modulation of the SERS intensity and ensuring overall nanoprobe stability. The further addition of a positively charged layer of poly (allylamine hydrocloride) on the surface of negatively charged SERS labels does not change the SERS response, but it promotes the penetration of GNSs in SH-SY5Y neuroblastoma cells. As an example of an application of such an approach, we demonstrate here the internalization of these new labels by means of visualization of cell morphology obtained with SERS mapping. PMID- 27199303 TI - Academic assessment of arterial pulse contour analysis: missing the forest for the trees? PMID- 27199304 TI - Applied cardiovascular physiology in theatre: measuring the cardiovascular effects of propofol anaesthesia. PMID- 27199305 TI - Monitoring consciousness under anaesthesia: the 21st century isolated forearm technique. PMID- 27199306 TI - Anaesthesia for awake craniotomy. PMID- 27199307 TI - Platelet function in paediatric cardiac surgery. PMID- 27199308 TI - New guideline for perioperative management of people with inherited salt-wasting alkaloses. PMID- 27199309 TI - Methodology of method comparison studies evaluating the validity of cardiac output monitors: a stepwise approach and checklist. AB - The validity of each new cardiac output (CO) monitor should be established before implementation in clinical practice. For this purpose, method comparison studies investigate the accuracy and precision against a reference technique. With the emergence of continuous CO monitors, the ability to detect changes in CO, in addition to its absolute value, has gained interest. Therefore, method comparison studies increasingly include assessment of trending ability in the data analysis. A number of methodological challenges arise in method comparison research with respect to the application of Bland-Altman and trending analysis. Failure to face these methodological challenges will lead to misinterpretation and erroneous conclusions. We therefore review the basic principles and pitfalls of Bland Altman analysis in method comparison studies concerning new CO monitors. In addition, the concept of clinical concordance is introduced to evaluate trending ability from a clinical perspective. The primary scope of this review is to provide a complete overview of the pitfalls in CO method comparison research, whereas other publications focused on a single aspect of the study design or data analysis. This leads to a stepwise approach and checklist for a complete data analysis and data representation. PMID- 27199310 TI - Efficacy and safety of intravenous lidocaine for postoperative analgesia and recovery after surgery: a systematic review with trial sequential analysis. AB - BACKGROUND: Improvement of postoperative pain and other perioperative outcomes remain a significant challenge and a matter of debate among perioperative clinicians. This systematic review aims to evaluate the effects of perioperative i.v. lidocaine infusion on postoperative pain and recovery in patients undergoing various surgical procedures. METHODS: CENTRAL, MEDLINE, EMBASE, and CINAHL databases and ClinicalTrials.gov, and congress proceedings were searched for randomized controlled trials until May 2014, that compared patients who did or did not receive continuous perioperative i.v. lidocaine infusion. RESULTS: Forty five trials (2802 participants) were included. Meta-analysis suggested that lidocaine reduced postoperative pain (visual analogue scale, 0 to 10 cm) at 1-4 h (MD -0.84, 95% CI -1.10 to -0.59) and at 24 h (MD -0.34, 95% CI -0.57 to -0.11) after surgery, but not at 48 h (MD -0.22, 95% CI -0.47 to 0.03). Subgroup analysis and trial sequential analysis suggested pain reduction for patients undergoing laparoscopic abdominal surgery or open abdominal surgery, but not for patients undergoing other surgeries. There was limited evidence of positive effects of lidocaine on postoperative gastrointestinal recovery, opioid requirements, postoperative nausea and vomiting, and length of hospital stay. There were limited data available on the effect of systemic lidocaine on adverse effects or surgical complications. Quality of evidence was limited as a result of inconsistency (heterogeneity) and indirectness (small studies). CONCLUSIONS: There is limited evidence suggesting that i.v. lidocaine may be a useful adjuvant during general anaesthesia because of its beneficial impact on several outcomes after surgery. PMID- 27199311 TI - The effect of propofol on haemodynamics: cardiac output, venous return, mean systemic filling pressure, and vascular resistances. AB - BACKGROUND: Although arterial hypotension occurs frequently with propofol use in humans, its effects on intravascular volume and vascular capacitance are uncertain. We hypothesized that propofol decreases vascular capacitance and therefore decreases stressed volume. METHODS: Cardiac output (CO) was measured using Modelflow((r)) in 17 adult subjects after upper abdominal surgery. Mean systemic filling pressure (MSFP) and vascular resistances were calculated using venous return curves constructed by measuring steady-state arterial and venous pressures and CO during inspiratory hold manoeuvres at increasing plateau pressures. Measurements were performed at three incremental levels of targeted blood propofol concentrations. RESULTS: Mean blood propofol concentrations for the three targeted levels were 3.0, 4.5, and 6.5 ug ml(-1). Mean arterial pressure, central venous pressure, MSFP, venous return pressure, Rv, systemic arterial resistance, and resistance of the systemic circulation decreased, stroke volume variation increased, and CO was not significantly different as propofol concentration increased. CONCLUSIONS: An increase in propofol concentration within the therapeutic range causes a decrease in vascular stressed volume without a change in CO. The absence of an effect of propofol on CO can be explained by the balance between the decrease in effective, or stressed, volume (as determined by MSFP), the decrease in resistance for venous return, and slightly improved heart function. CLINICAL TRIAL REGISTRATION: Netherlands Trial Register: NTR2486. PMID- 27199312 TI - Greater intravenous fluid volumes are associated with prolonged recovery after colorectal surgery: a retrospective cohort study. AB - BACKGROUND: We carried out a retrospective assessment of whether perioperative fluid volume was associated with length of hospital stay (LOS) after colorectal surgery. METHODS: A single-centre chart review was conducted on colorectal surgeries that took place between January 2008 and December 2013. The primary outcome was LOS, with prolonged LOS defined as greater than median LOS. Secondary outcomes included postoperative pulmonary oedema, acute renal failure, myocardial infarction, and mortality. Univariate analysis, multivariable logistic regression, and quantile regression analyses were conducted to examine the association between perioperative fluid volume and prolonged LOS. RESULTS: Of the 1242 procedures, 57% were elective, 62% oncological, and 31% laparoscopic. The median LOS was 8.2 days (interquartile range 5.2, 14.7). Patients received 3.2 (sd 1.5) litres of fluid in the perioperative period (operating and recovery rooms), predominantly crystalloid. The volume (in litres) of perioperative fluid was independently associated with prolonged LOS (odds ratio 1.23, 95% confidence interval 1.10-1.36, P<0.01). This association persisted across the spectrum of definitions for prolonged LOS (10th-90th percentile). Logistic regression analysis also revealed that prolonged LOS was associated with age >65 yr, Charlson Co-morbidity Index >=3, use of colloids, emergent surgery, estimated blood loss >200 ml, preoperative anaemia, erythrocyte transfusion, open surgeries, and surgical duration >4 h (C-statistic=0.79, Hosmer-Lemeshow=0.36). CONCLUSIONS: Greater perioperative fluid volume was independently associated with prolonged duration of recovery across a spectrum of surgical risk profiles. Fluid restriction should be considered a part of the care package in enhanced recovery after surgery programmes for colorectal surgery. PMID- 27199313 TI - Perioperative monitoring of platelet function in paediatric cardiac surgery by thromboelastometry, or platelet aggregometry? AB - BACKGROUND: Impaired platelet function increases the risk of bleeding complications in cardiac surgery. Reliable assessment of platelet function can improve treatment. We investigated whether thromboelastometry detects clinically significant preoperative, perioperative, and postoperative adenosine diphosphate (ADP)-dependent platelet dysfunction in paediatric cardiac surgery patients. METHODS: Fifty-seven children were included in a single-centre prospective observational study. Clot formation (modified rotational thromboelastometry with heparinase, HEPTEM) and platelet aggregation (multiple electrode aggregometry) were analysed at five time points before, during, and after surgery. The accuracy of thromboelastometric indices of platelet function [maximal clot firmness (MCF) and clot formation time (CFT)] to detect ADP-dependent platelet dysfunction (defined as ADP-induced aggregation <=30 units) was calculated with receiver operating characteristics analysis, which also identified optimal cut-off levels. Positive and negative predictive values for the identified cut-off levels (CFT>=166 s; MCF<=43 mm) to detect platelet function were determined. RESULTS: The MCF and CFT were highly accurate in predicting platelet dysfunction during cardiopulmonary bypass [CPB; area under the aggregation curve 0.89 (95% confidence interval 0.80-0.97) and 0.86 (0.77-0.96), respectively] but not immediately after CPB [0.64 (0.48-0.79) and 0.67 (0.52-0.82), respectively] or on arrival at the intensive care unit [0.53 (0.37-0.69) and 0.60 (0.44-0.77), respectively]. The positive and negative predictive values were acceptable during CPB (87 and 67%, respectively, for MCF<=43 mm; 80 and 100% for CFT>=166 s) but markedly lower after surgery. CONCLUSION: In paediatric cardiac surgery, thromboelastometry has acceptable ability to detect ADP-dependent platelet dysfunction during, but not after, CPB. PMID- 27199315 TI - Increasing positive end-expiratory pressure (re-)improves intraoperative respiratory mechanics and lung ventilation after prone positioning. AB - BACKGROUND: Turning a patient prone, changes the respiratory mechanics and potentially the level of positive end-expiratory pressure (PEEP) that is necessary to prevent alveolar collapse. In this prospective clinical study we examined the impact of PEEP on the intratidal respiratory mechanics and regional lung aeration in the prone position. We hypothesized that a higher PEEP is required to maintain compliance and regional ventilation in the prone position. METHODS: After ethical approval, 45 patients with healthy lungs undergoing lumbar spine surgery were examined in the supine position at PEEP 6 cm H2O and in the prone position at PEEP (6, 9 and 12 cm H2O). Dynamic compliance (CRS) and intratidal compliance-volume curves were determined and regional ventilation was measured using electrical impedance tomography. The compliance-volume curves were classified to indicate intratidal derecruitment, overdistension, or neither. RESULTS: CRS did not differ between postures and PEEP levels (P>0.28). At a PEEP of 6 cm H2O a compliance-volume profile indicating neither derecruitment nor overdistension was observed in 38 supine, but only in 20 prone positioned patients (P<0.001). The latter increased to 33 and 37 (both P<0.001) when increasing PEEP to 9 and 12 cm H2O, respectively. Increasing PEEP from 6 to 9 cm H2O in the prone position increased peripheral ventilation significantly. CONCLUSIONS: Respiratory system mechanics change substantially between supine and prone posture, which is not demonstrated in routine measurements. The intratidal compliance analysis suggests that in most patients a PEEP above commonly used settings is necessary to avoid alveolar collapse in the prone position. CLINICAL TRIAL REGISTRATION: DRKS 00005692. PMID- 27199314 TI - The role of peripheral afferents in persistent inguinal postherniorrhaphy pain: a randomized, double-blind, placebo-controlled, crossover trial of ultrasound guided tender point blockade. AB - BACKGROUND: Severe, persistent inguinal postherniorrhaphy pain (PIPP) is a debilitating condition that develops in 2-5% of patients. PIPP may be neuropathic in nature, yet the lesion in the peripheral nervous system has not been located. Most PIPP-patients demonstrate a tender point (TP) in the medial aspect of the inguinal region that triggers pain upon minimal pressure. As TPs may play a role in the pathophysiology of PIPP, the aim of this trial was to investigate the analgesic effects of local anaesthetic TP-blockade. METHODS: A randomized, double blind, placebo-controlled, crossover trial was performed in 14 PIPP-patients and six healthy volunteers. All participated in two sessions, seven days apart, receiving 10 ml of 0.25% bupivacaine or normal saline via an ultrasound-guided fascial plane block at the TP. The TP-area was used for pain assessments (at rest, on movement, with 100 kPa pressure-algometry) and quantitative sensory testing (pressure pain thresholds, thermal detection/pain thresholds, supra threshold heat perception), before and after the TP-blockade. RESULTS: The median (95% CI) reduction in pain was 63% (44.1 to 73.6%) after bupivacaine compared with 36% (11.6 to 49.7%; P=0.003) after placebo. Significant increases in cool detection (P=0.01) and pressure pain thresholds (P=0.009) with decreases in supra threshold heat pain perception (P=0.003) were seen after bupivacaine only. In four out of six volunteers, increased thermal and evoked-pain thresholds after bupivacaine compared with placebo, was demonstrated. CONCLUSIONS: This trial demonstrates that peripheral afferent input from the TP-area is important for maintenance of spontaneous and evoked pain in PIPP. CLINICAL TRIAL REGISTRATION: NCT02065219. PMID- 27199316 TI - Immediate postoperative extubation in bilateral lung transplantation: predictive factors and outcomes. AB - BACKGROUND: We reviewed our experience with tracheal extubation in the operating room (E-OR) among cystic fibrosis patients requiring bilateral lung transplantation to evaluate safety and determine predictive factors of E-OR. METHODS: The charts of 89 recipients (from May 2007 to June 2013) were analysed. Patients were divided into E-OR and E-ICU (intensive care unit extubation) groups. Data are expressed as numbers (percentages) or medians [25th-75th percentiles]. RESULTS: There were 41 patients in the E-OR group (46%). Donor and recipient characteristics were similar between groups. Intraoperative complications occurred less frequently in the E-OR group, and fluid and transfusion requirements were lower. Postoperative courses were different in the E-OR group, including a lower rate of grade 3 primary graft dysfunction (0 compared with 19 patients, P<0.0001) and shorter ICU (5.0 [3.7-7.2] compared with 11.5 [7.0-15.5] days) and hospital stays (22.0 [18.0-25.5] compared with 33.0 [25.0-56.5] days, respectively; P<0.0001 for both). The 1 yr survival rates were similar: 95% in the E-OR group and 98% in the E-ICU group. A statistical model built on a development cohort of 60 randomly selected patients predicted 95% of E OR instances in this cohort and 82% of E-OR instances in the validation cohort (28 patients). Predictive factors were complications during single-lung ventilation (second graft implantation), complications during bipulmonary ventilation (end of surgery), and the ratio of arterial partial pressure of oxygen to fractional inspired oxygen (end of surgery). CONCLUSIONS: Our protocol allowed for extubation of 46% of bilateral lung transplant patients without increased postoperative risks. PMID- 27199317 TI - Effect of positive end-expiratory pressure on pulmonary shunt and dynamic compliance during abdominal surgery. AB - BACKGROUND: General anaesthesia decreases pulmonary compliance and increases pulmonary shunt due to the development of atelectasis. The presence of capnoperitoneum during laparoscopic surgery may further decrease functional residual capacity, promoting an increased amount of atelectasis compared with laparotomy. The aim of this study was to evaluate the effects of different levels of positive end-expiratory pressure (PEEP) in both types of surgery and to investigate whether higher levels of PEEP should be used during laparoscopic surgery. METHODS: This prospective observational study included 52 patients undergoing either laparotomy or laparoscopic surgery. Three levels of PEEP were applied in random order: (1) zero (ZEEP), (2) 5 cmH2O and (3) 10 cmH2O. Pulmonary shunt and ventilation/perfusion mismatch were assessed by the automatic lung parameter estimator system. RESULTS: Pulmonary shunt was similar in both groups. However, in laparotomy, a PEEP of 5 cmH2O significantly decreased shunt when compared with ZEEP (12 vs 6%; P=0.001), with additional PEEP having no further effect. In laparoscopic surgery, a significant reduction in shunt (13 vs 6%; P=0.001) was obtained only at a PEEP of 10 cmH2O. Although laparoscopic surgery was associated with a lower pulmonary compliance, increasing levels of PEEP were able to ameliorate it in both groups. CONCLUSION: Both surgeries have similar negative effects on pulmonary shunt, while the presence of capnoperitoneum reduced only the pulmonary compliance. It appears that a more aggressive PEEP level is required to reduce shunt and to maximize compliance in case of laparoscopic surgery. PMID- 27199319 TI - Isoflurane enhances the malignant potential of glioblastoma stem cells by promoting their viability, mobility in vitro and migratory capacity in vivo. AB - BACKGROUND: Isoflurane is one of the most common general anaesthetics used during surgical procedures, including tumour resection. However, the effects of isoflurane on the viability and migration capacity of cancer cells, specifically in the context of brain cancer cells, remain unclear. Therefore, the aim of this study was to evaluate the influence that isoflurane has on the function of glioblastoma stem cells (GCSs) in regards to cell proliferation, survival and migration. METHOD: U251-GSCs were exposed to isoflurane at clinically relevant concentrations and incubation times. The effects on proliferation, survival and migration capacities of the cells were evaluated in vitro. The potential risk was assessed in mice by intracranial injection of U251-GSCs pretreated with isoflurane. Furthermore, the average tumour volume and migration distance of U251 GSCs from the tumour centre were calculated. RESULTS: Exposure of U251-GSCs to 1.2% isoflurane for 6 h resulted in increased proliferation (P<0.05) and decreased apoptosis rate (P<0.05) when compared with the control group. In addition, isoflurane exposure caused increased migration capacity in vitro (P<0.05) and the distance migrated was increased in vivo (P<0.05). CONCLUSION: Clinically relevant concentrations and incubation times of isoflurane could promote the viability and mobility of U251-GSCs, suggesting this general anaesthetic may have detrimental effects in glioblastoma by facilitating its growth and migration. PMID- 27199318 TI - Detection of optimal PEEP for equal distribution of tidal volume by volumetric capnography and electrical impedance tomography during decreasing levels of PEEP in post cardiac-surgery patients. AB - BACKGROUND: Homogeneous ventilation is important for prevention of ventilator induced lung injury. Electrical impedance tomography (EIT) has been used to identify optimal PEEP by detection of homogenous ventilation in non-dependent and dependent lung regions. We aimed to compare the ability of volumetric capnography and EIT in detecting homogenous ventilation between these lung regions. METHODS: Fifteen mechanically-ventilated patients after cardiac surgery were studied. Ventilator settings were adjusted to volume-controlled mode with a fixed tidal volume (Vt) of 6-8 ml kg(-1) predicted body weight. Different PEEP levels were applied (14 to 0 cm H2O, in steps of 2 cm H2O) and blood gases, Vcap and EIT were measured. RESULTS: Tidal impedance variation of the non-dependent region was highest at 6 cm H2O PEEP, and decreased significantly at 14 cm H2O PEEP indicating decrease in the fraction of Vt in this region. At 12 cm H2O PEEP, homogenous ventilation was seen between both lung regions. Bohr and Enghoff dead space calculations decreased from a PEEP of 10 cm H2O. Alveolar dead space divided by alveolar Vt decreased at PEEP levels <=6 cm H2O. The normalized slope of phase III significantly changed at PEEP levels <=4 cm H2O. Airway dead space was higher at higher PEEP levels and decreased at the lower PEEP levels. CONCLUSIONS: In postoperative cardiac patients, calculated dead space agreed well with EIT to detect the optimal PEEP for an equal distribution of inspired volume, amongst non-dependent and dependent lung regions. Airway dead space reduces at decreasing PEEP levels. PMID- 27199322 TI - Inhaled sedation in acute brain injury patients. PMID- 27199321 TI - Paradox of the incidence of postoperative nausea and vomiting after xenon-based anaesthesia. PMID- 27199320 TI - High inspired oxygen concentration increases the speed of onset of remifentanil induced respiratory depression. PMID- 27199323 TI - Reply. PMID- 27199324 TI - Intrajugular ballon catheter will not abolish venous air embolism or its consequences. PMID- 27199325 TI - Do we need a manual jugular venous compression manoeuvre? PMID- 27199326 TI - More evidence is needed regarding intraoperative hypotension and delirium after cardiac surgery. PMID- 27199327 TI - Intraoperative hypotension and postoperative delirium: no confusion on confounding. PMID- 27199328 TI - Reliable critical care: how knowledge translation can result in patient harm. PMID- 27199330 TI - VentrainTM ejector ventilator: it ejects more than air. PMID- 27199329 TI - Reply. PMID- 27199331 TI - VentrainTM does not make up for needle cricothyroidotomy deficiencies. PMID- 27199332 TI - Misuse of 'trend' to describe 'almost significant' differences in anaesthesia research. PMID- 27199333 TI - Reply. PMID- 27199334 TI - 'Trend' and 'almost significant' in anaesthesia research. PMID- 27199335 TI - Reply. PMID- 27199336 TI - Most of the time, P is an unreliable marker, so we need no exact cut-off. PMID- 27199344 TI - Femtosecond laser-controlled self-assembly of amorphous-crystalline nanogratings in silicon. AB - Self-assembly (SA) of molecular units to form regular, periodic extended structures is a powerful bottom-up technique for nanopatterning, inspired by nature. SA can be triggered in all classes of solid materials, for instance, by femtosecond laser pulses leading to the formation of laser-induced periodic surface structures (LIPSS) with a period slightly shorter than the laser wavelength. This approach, though, typically involves considerable material ablation, which leads to an unwanted increase of the surface roughness. We present a new strategy to fabricate high-precision nanograting structures in silicon, consisting of alternating amorphous and crystalline lines, with almost no material removal. The strategy can be applied to static irradiation experiments and can be extended into one and two dimensions by scanning the laser beam over the sample surface. We demonstrate that lines and areas with parallel nanofringe patterns can be written by an adequate choice of spot size, repetition rate and scan velocity, keeping a constant effective pulse number (N eff) per area for a given laser wavelength. A deviation from this pulse number leads either to inhomogeneous or ablative structures. Furthermore, we demonstrate that this approach can be used with different laser systems having widely different wavelengths (1030 nm, 800 nm, 400 nm), pulse durations (370 fs, 100 fs) and repetition rates (500 kHz, 100 Hz, single pulse) and that the grating period can also be tuned by changing the angle of laser beam incidence. The grating structures can be erased by irradiation with a single nanosecond laser pulse, triggering recrystallization of the amorphous stripes. Given the large differences in electrical conductivity between the two phases, our structures could find new applications in nanoelectronics. PMID- 27199343 TI - Understanding Intratumoral Heterogeneity: Lessons from the Analysis of At-Risk Tissue and Premalignant Lesions in the Colon. AB - Advances in DNA sequencing have created new opportunities to better understand the biology of cancers. Attention is currently focused on precision medicine: does a cancer carry a mutation that is targetable with already available drugs? But, the timing at which multiple, targetable mutations arise during the adenoma to carcinoma sequence remains unresolved. Borras and colleagues identified mutations and allelic imbalance in at-risk mucosa and early polyps in the human colon. Their analyses indicate that mutations in key genes can arise quite early during tumorigenesis and that polyps are often multiclonal with at least two clones. These results are consistent with the "Big Bang" model of tumorigenesis, which postulates that intratumoral heterogeneity is a consequence of a mutational burst in the first few cell divisions following initiation that drives divergence from a single founder with unique but related clones coevolving. Emerging questions center around the ancestry of the tumor and impact of early intratumoral heterogeneity on tumor establishment, growth, progression, and most importantly, response to therapeutic intervention. Additional sequencing studies in which samples, especially at-risk tissue and premalignant neoplasms, are analyzed from animal models and humans will further our understanding of tumorigenesis and lead to more effective strategies for prevention and treatment. Cancer Prev Res; 9(8); 638-41. (c)2016 AACRSee related article by Borras, et al., Cancer Prev Res 2016;9(6):417-427. PMID- 27199345 TI - Paraburkholderia nodosa is the main N2-fixing species trapped by promiscuous common bean (Phaseolus vulgaris L.) in the Brazilian 'Cerradao'. AB - The bacterial genus Burkholderia comprises species occupying several habitats, including a group of symbionts of leguminous plants-also called beta-rhizobia that has been recently ascribed to the new genus Paraburkholderia We used common bean (Phaseolus vulgaris L.) plants to trap rhizobia from an undisturbed soil of the Brazilian Cerrado under the vegetation type 'Cerradao'. Genetic characterization started with the analyses of 181 isolates by BOX-PCR, where the majority revealed unique profiles, indicating high inter- and intra-species diversity. Restriction fragment length polymorphism-PCR of the 16S rRNA of representative strains of the BOX-PCR groups indicated two main clusters, and gene-sequencing analysis identified the minority (27%) as Rhizobium and the majority (73%) as Paraburkholderia Phylogenetic analyses of the 16S rRNA and housekeeping (recA and gyrB) genes positioned all strains of the second cluster in the species P. nodosa, and the phylogeny of a symbiotic gene-nodC-was in agreement with the conserved genes. All isolates were stable vis-a-vis nodulating common bean, but, in general, with a low capacity for fixing N2, although some effective strains were identified. The predominance of P. nodosa might be associated with the edaphic properties of the Cerrado biome, and might represent an important role in terms of maintenance of the ecosystem, which is characterized by acid soils with high saturation of aluminum and low N2 content. PMID- 27199347 TI - Promiscuous and specific bacterial symbiont acquisition in the amoeboid genus Nuclearia (Opisthokonta). AB - We isolated 17 strains of the amoeboid genus Nuclearia (Opisthokonta) from five Swiss lakes. Eight of these nucleariid isolates were associated with bacterial endosymbionts and/or ectosymbionts. Amoebae were characterized morphologically and by their 18S rRNA genes. Phylogeny based on molecular data resulted in four established monophyletic branches and two new clusters. A heterogeneous picture emerged by highlighting nucleariids with associated bacteria. Apart from one cluster which consisted of only isolates with and three groups of amoebae without symbionts, we also found mixed clusters. The picture got even more 'blurred' by regarding the phylogeny of symbiotic bacteria. Although seven different bacterial strains could be identified, it seems that we still are only scratching the surface of symbionts' diversity. Furthermore, types of symbioses might be different depending on host species. Strains of Nuclearia thermophila harboured the same endosymbiont even when isolated from different lakes. This pointed to a specific and obligate interaction. However, two isolates of N. delicatula were associated with different endosymbiotic bacteria. Here the symbiont acquisition seemed to be rather promiscuous. This behaviour regarding symbiotic associations is especially remarkable considering the phylogenetic position of these basal opisthokonts. PMID- 27199346 TI - Role of secondary metabolites in the interaction between Pseudomonas fluorescens and soil microorganisms under iron-limited conditions. AB - Microorganisms can be versatile in their interactions with each other, being variously beneficial, neutral or antagonistic in their effect. Although this versatility has been observed among many microorganisms and in many environments, little is known regarding the mechanisms leading to these changes in behavior. In the present work, we analyzed the mechanism by which the soil bacterium Pseudomonas fluorescens BBc6R8 shifts from stimulating the growth of the ectomycorrhizal fungus Laccaria bicolor S238N to killing the fungus. We show that among the three secondary metabolites produced by the bacterial strain-the siderophores enantio-pyochelin and pyoverdine, and the biosurfactant viscosin-the siderophores are mainly responsible for the antagonistic activity of the bacterium under iron-limited conditions. While the bacterial strain continues to produce beneficial factors, their effects are overridden by the action of their siderophores. This antagonistic activity of the strain P. fluorescens BBC6R8 in iron-depleted environments is not restricted to its influence on L. bicolor, since it was also seen to inhibit the growth of the actinomycete Streptomyces ambofaciens ATCC23877. We show that the strain P. fluorescens BBc6R8 uses different strategies to acquire iron, depending on certain biotic and abiotic factors. PMID- 27199351 TI - The jump-into-contact effect in biased AFM probes on dielectric films and its application to quantify the dielectric permittivity of thin layers. AB - The jump-into-contact (JIC) phenomenon in biased atomic force microscopy (AFM) probes on dielectric films is studied. The influence of the film thickness on the position at which the AFM tip collapses irreversibly into the sample surface was theoretically analyzed using a widely accepted analytical expression of the probe sample electrostatic interaction force. It was demonstrated that for relatively high values of voltage (V > 10-20 V) applied between the probe and the substrate the cantilever deflection at the JIC is independent of the dielectric film thickness for thin-ultrathin layers (h < 10-50 nm). Under the same conditions the z-piezo distance at the JIC follows approximately a linear behavior with the film thickness. Based on this effect an empirical model was formulated to estimate the dielectric permittivity of thin/ultrathin dielectric films using the jump-into contact distance. The procedure was successfully applied on thin PVD-SiO2 films, obtaining good agreement with a dielectric constant value previously reported for the same material. PMID- 27199348 TI - Metastasis Stimulation by Hypoxia and Acidosis-Induced Extracellular Lipid Uptake Is Mediated by Proteoglycan-Dependent Endocytosis. AB - Hypoxia and acidosis are inherent stress factors of the tumor microenvironment and have been linked to increased tumor aggressiveness and treatment resistance. Molecules involved in the adaptive mechanisms that drive stress-induced disease progression constitute interesting candidates of therapeutic intervention. Here, we provide evidence of a novel role of heparan sulfate proteoglycans (HSPG) in the adaptive response of tumor cells to hypoxia and acidosis through increased internalization of lipoproteins, resulting in a lipid-storing phenotype and enhanced tumor-forming capacity. Patient glioblastoma tumors and cells under hypoxic and acidic stress acquired a lipid droplet (LD)-loaded phenotype, and showed an increased recruitment of all major lipoproteins, HDL, LDL, and VLDL. Stress-induced LD accumulation was associated with increased spheroid-forming capacity during reoxygenation in vitro and lung metastatic potential in vivo On a mechanistic level, we found no apparent effect of hypoxia on HSPGs, whereas lipoprotein receptors (VLDLR and SR-B1) were transiently upregulated by hypoxia. Importantly, however, using pharmacologic and genetic approaches, we show that stress-mediated lipoprotein uptake is highly dependent on intact HSPG expression. The functional relevance of HSPG in the context of tumor cell stress was evidenced by HSPG-dependent lipoprotein cell signaling activation through the ERK/MAPK pathway and by reversal of the LD-loaded phenotype by targeting of HSPGs. We conclude that HSPGs may have an important role in the adaptive response to major stress factors of the tumor microenvironment, with functional consequences on tumor cell signaling and metastatic potential. Cancer Res; 76(16); 4828-40. (c)2016 AACR. PMID- 27199349 TI - miR-29b Mediates NF-kappaB Signaling in KRAS-Induced Non-Small Cell Lung Cancers. AB - A global understanding of miRNA function in EGFR signaling pathways may provide insights into improving the management of KRAS-mutant lung cancers, which remain relatively recalcitrant to treatment. To identify miRNAs implicated in EGFR signaling, we transduced bronchial epithelial BEAS-2B cells with retroviral vectors expressing KRAS(G12V) and monitored miRNA expression patterns by microarray analysis. Through this approach, we defined miR-29b as an important target for upregulation by mutant KRAS in non-small cell lung cancers. Cell biologic analyses showed that pharmacologic inhibition of EGFR or MEK was sufficient to reduce levels of miR-29b, while PI3K inhibition had no effect. In KRAS(G12V)-transduced BEAS-2B cells, introduction of anti-miR-29b constructs increased the sensitivity to apoptosis, arguing that miR-29b mediated apoptotic resistance conferred by mutant KRAS. Mechanistic investigations traced this effect to the ability of miR-29b to target TNFAIP3/A20, a negative regulator of NF-kappaB signaling. Accordingly, overexpression of an miR-29b-refractory isoform of TNFAIP3 restored NF-kappaB and extrinsic apoptosis, confirming that TNFAIP3 is a functionally relevant target of miR-29b. We also noted that miR-29b could confer sensitivity to intrinsic apoptosis triggered by exposure to cisplatin, a drug used widely in lung cancer treatment. Thus, miR-29b expression may tilt cells from extrinsic to intrinsic mechanisms of apoptosis. Overall, our results reveal a complexity in cancer for miR-29b, which can act as either an oncogene or tumor suppressor gene depending on signaling context. Cancer Res; 76(14); 4160-9. (c)2016 AACR. PMID- 27199352 TI - Strain-modulated electronic and thermal transport properties of two-dimensional O silica. AB - Silica is one of the most abundant materials in the Earth's crust and is a remarkably versatile and important engineering material in various modern science and technology. Recently, freestanding and well-ordered two-dimensional (2D) silica monolayers with octahedral (O-silica) building blocks were found to be theoretically stable by (Wang G et al 2015 J. Phys. Chem. C 119 15654-60). In this paper, by performing first-principles calculations, we systematically investigated the electronic and thermal transport properties of 2D O-silica and also studied how these properties can be tuned by simple mechanical stretching. Unstrained 2D O-silica is an insulator with an indirect band gap of 6.536 eV. The band gap decreases considerably with bilateral strain up to 29%, at which point a semiconductor-metal transition occurs. More importantly, the in-plane thermal conductivity of freestanding 2D O-silica is found to be unusually high, which is around 40 to 50 times higher than that of bulk alpha-quartz and more than two orders of magnitude higher than that of amorphous silica. The thermal conductivity of O-silica decreases by almost two orders of magnitude when the bilateral stretching strain reaches 10%. By analyzing the mode-dependent phonon properties and phonon-scattering channel, the phonon lifetime is found to be the dominant factor that leads to the dramatic decrease of the lattice thermal conductivity under strain. The very sensitive response of both band gap and phonon transport properties to the external mechanical strain will enable 2D O silica to easily adapt to the different environment of realistic applications. Our study is expected to stimulate experimental exploration of further physical and chemical properties of 2D silica systems, and offers perspectives on modulating the electronic and thermal properties of related low-dimensional structures for applications such as thermoelectric, photovoltaic, and optoelectronic devices. PMID- 27199350 TI - Industrial production of acetone and butanol by fermentation-100 years later. AB - Microbial production of acetone and butanol was one of the first large-scale industrial fermentation processes of global importance. During the first part of the 20th century, it was indeed the second largest fermentation process, superseded in importance only by the ethanol fermentation. After a rapid decline after the 1950s, acetone-butanol-ethanol (ABE) fermentation has recently gained renewed interest in the context of biorefinery approaches for the production of fuels and chemicals from renewable resources. The availability of new methods and knowledge opens many new doors for industrial microbiology, and a comprehensive view on this process is worthwhile due to the new interest. This thematic issue of FEMS Microbiology Letters, dedicated to the 100th anniversary of the first industrial exploitation of Chaim Weizmann's ABE fermentation process, covers the main aspects of old and new developments, thereby outlining a model development in biotechnology. All major aspects of industrial microbiology are exemplified by this single process. This includes new technologies, such as the latest developments in metabolic engineering, the exploitation of biodiversity and discoveries of new regulatory systems such as for microbial stress tolerance, as well as technological aspects, such as bio- and down-stream processing. PMID- 27199353 TI - Use of Simultaneous 18F-FDG PET/MRI for the Detection of Spondylodiskitis. AB - The diagnosis of spondylodiskitis is often challenging. MRI is quite sensitive but lacks specificity, and distinction from erosive osteochondritis is often difficult. We sought to assess the diagnostic value of (18)F-FDG PET combined with MRI (combined (18)F-FDG PET/MRI) in patients with suspected spondylodiskitis and an inconclusive clinical or MRI presentation. METHODS: In a prospective study, 30 patients with previous inconclusive MRI results and suspected spondylodiskitis underwent combined (18)F-FDG PET/MRI, including precontrast and postcontrast standard spine MRI sequences. The image datasets were evaluated on dedicated workstations by 2 radiology residents and 1 board-certified nuclear medicine physician independently and then in consensus. Because of severe susceptibility artifacts, only 28 of 30 image datasets were evaluable, with a total of 29 regions of suspected spondylodiskitis. SUV ratios (affected disk/reference disk) were determined. The imaging results were compared with histopathology or clinical follow-up as a reference standard and subjected to statistical analysis. RESULTS: The reference standards identified spondylodiskitis in 12 disks and excluded spondylodiskitis in 17 disks. For MRI alone, the sensitivity was 50%, the specificity was 71%, the positive predictive value was 54%, and the negative predictive value was 67%. Adding the PET data resulted in sensitivity, specificity, positive predictive value, and negative predictive value of 100%, 88%, 86%, and 100%, respectively. In a receiver operating characteristic curve analysis, an SUVmax ratio threshold of 2.1 resulted in 92% sensitivity and 88% specificity (area under the receiver operating characteristic curve, 0.95). Neither the level of C-reactive protein nor the leukocyte count at the time of PET/MRI was related to the reference standard diagnosis of spondylodiskitis. CONCLUSION: In patients with inconclusive clinical or MRI findings, the use of (18)F-FDG PET/MRI significantly increased diagnostic certainty for the detection of spondylodiskitis. PMID- 27199354 TI - Imaging the Biodistribution and Performance of Transplanted Stem Cells with PET. PMID- 27199355 TI - Noninvasive PET Imaging and Tracking of Engineered Human Muscle Precursor Cells for Skeletal Muscle Tissue Engineering. AB - Transplantation of human muscle precursor cells (hMPCs) is envisioned for the treatment of various muscle diseases. However, a feasible noninvasive tool to monitor cell survival, migration, and integration into the host tissue is still missing. METHODS: In this study, we designed an adenoviral delivery system to genetically modify hMPCs to express a signaling-deficient form of human dopamine D2 receptor (hD2R). The gene expression levels of the receptor were evaluated by reverse transcriptase polymerase chain reaction, and infection efficiency was evaluated by fluorescent microscopy. The viability, proliferation, and differentiation capacity of the transduced cells, as well as their myogenic phenotype, were determined by flow cytometry analysis and fluorescent microscopy. (18)F-fallypride and (18)F-fluoromisonidazole, two well-established PET radioligands, were assessed for their potential to image engineered hMPCs in a mouse model and their uptakes were evaluated at different time points after cell inoculation in vivo. Biodistribution studies, autoradiography, and PET experiments were performed to determine the extent of signal specificity. To address feasibility for tracking hMPCs in an in vivo model, the safety of the adenoviral gene delivery was evaluated. Finally, the harvested tissues were histologically examined to determine whether survival of the transplanted cells was sustained at different time points. RESULTS: Adenoviral gene delivery was shown to be safe, with no detrimental effects on the primary human cells. The viability, proliferation, and differentiation capacity of the transduced cells were confirmed, and flow cytometry analysis and fluorescent microscopy showed that their myogenic phenotype was sustained. (18)F-fallypride and (18)F fluoromisonidazole were successfully synthesized. Specific binding of (18)F fallypride to hD2R hMPCs was demonstrated in vitro and in vivo. Furthermore, the (18)F-fluoromisonidazole signal was high at the early stages. Finally, sustained survival of the transplanted cells at different time points was confirmed histologically, with formation of muscle tissue at the site of injection. CONCLUSION: Our proposed use of a signaling-deficient hD2R as a potent reporter for in vivo hMPC PET tracking by (18)F-fallypride is a significant step toward potential noninvasive tracking of hD2R hMPCs and bioengineered muscle tissues in the clinic. PMID- 27199357 TI - Advanced Molecular Imaging for Exploring Classic Conditioning and Extinction. PMID- 27199358 TI - Highlights from the Updated Joint ASNC/SNMMI PET Myocardial Perfusion and Metabolism Clinical Imaging Guidelines. PMID- 27199356 TI - Preclinical Evaluation of 18F-PF-05270430, a Novel PET Radioligand for the Phosphodiesterase 2A Enzyme. AB - The enzyme phosphodiesterase 2A (PF-05270430) is a potential target for development of novel therapeutic agents for the treatment of cognitive impairments. The goal of the present study was to evaluate the PDE2A ligand (18)F PF-05270430, 4-(3-fluoroazetidin-1-yl)-7-methyl-5-(1-methyl-5-(4 (trifluoromethyl)phenyl)-1H-pyrazol-4-yl)imidazo[1,5-f][1,2,4]triazine, in nonhuman primates. METHODS: (18)F-PF-05270430 was radiolabeled by 2 methods via nucleophilic substitution of its tosylate precursor. Tissue metabolite analysis in rodents and PET imaging in nonhuman primates under baseline and blocking conditions were performed to determine the pharmacokinetic and binding characteristics of the new radioligand. Various kinetic modeling approaches were assessed to select the optimal method for analysis of imaging data. RESULTS: (18)F-PF-05270430 was synthesized in greater than 98% radiochemical purity and high specific activity. In the nonhuman primate brain, uptake of (18)F-PF 05270430 was fast, with peak concentration (SUVs of 1.5-1.8 in rhesus monkeys) achieved within 7 min after injection. The rank order of uptake was striatum > neocortical regions > cerebellum. Regional time-activity curves were well fitted by the 2-tissue-compartment model and the multilinear analysis-1 (MA1) method to arrive at reliable estimates of regional distribution volume (VT) and binding potential (BPND) with 120 min of scan data. Regional VT values (MA1) ranged from 1.28 mL/cm(3) in the cerebellum to 3.71 mL/cm(3) in the putamen, with a BPND of 0.25 in the temporal cortex and 1.92 in the putamen. Regional BPND values estimated by the simplified reference tissue model (SRTM) were similar to those from MA1. Test-retest variability in high-binding regions (striatum) was 4% +/- 6% for MA1 VT, 13% +/- 6% for MA1 BPND, and 13% +/- 7% SRTM BPND, respectively. Pretreatment of animals with the PDE2A inhibitor PF-05180999 resulted in a dose dependent reduction of (18)F-PF-05270430 specific binding, with a half maximal effective concentration of 69.4 ng/mL in plasma PF-05180999 concentration. CONCLUSION: (18)F-PF-05270430 displayed fast and reversible kinetics in nonhuman primates, as well as specific binding blockable by a PDE2A inhibitor. This is the first PET tracer with desirable imaging properties and demonstrated ability to image and quantify PDE2A in vivo. PMID- 27199359 TI - Reply: Risk of Breast Cancer in Patients with Thyroid Cancer Receiving 131I Treatment: Is There an Immortal Time Bias? PMID- 27199361 TI - 18F-Fluciclovine (FACBC) and Its Potential Use for Breast Cancer Imaging. PMID- 27199360 TI - Ex Vivo Tracing of NMDA and GABA-A Receptors in Rat Brain After Traumatic Brain Injury Using 18F-GE-179 and 18F-GE-194 Autoradiography. AB - In vivo imaging of N-methyl-d-aspartate (NMDA) glutamate receptor and gamma aminobutyric acid (GABA)-A receptor during progression of brain pathology is challenging because of the lack of imaging tracers with high affinity and specificity. METHODS: We monitored changes in NMDA receptor and GABA-A receptor in a clinically relevant model of traumatic brain injury (TBI) induced by lateral fluid percussion in adult rats, using 2 new ligands for PET: (18)F-GE-179 for the open/active state of the NMDA receptor ion channel and (18)F-GE-194 for GABA-A receptor. Ex vivo brain autoradiography of radioligands was performed at subacute (5-6 d) and chronic (40-42 d) time points after TBI. RESULTS: At 5-6 d after TBI, (18)F-GE-179 binding was higher in the cortical lesion area, in the lesion core, and in the hippocampus than in the corresponding contralateral regions; this increase was probably related to increased permeability of the blood-brain barrier. At 40-42 d after TBI, (18)F-GE-179 binding was significantly higher in the medial cortex, in the corpus callosum, and in the thalamus than in the corresponding contralateral regions. Five to 6 days after TBI, (18)F-GE-194 binding was significantly higher in the lesion core and significantly lower in the ipsilateral thalamus. By 40-42 d after TBI, the reduction in (18)F-GE-194 binding extended to the cortical lesion, including the perilesional cortex around the lesion core. The reduction in thalamic binding was more extensive at 40-42 d than at 5-6 d after TBI, suggesting a progressive decrease in thalamic GABA-A receptor density. Immunohistochemistry against GABA-A alpha1 subunit revealed a similar decrease to (18)F-GE-194 binding, particularly during the chronic phase. CONCLUSION: Our data support the validity of novel (18)F-GE-179 and (18)F-GE-194 radioligands for the detection of changes in active NMDA receptor and GABA-A receptor in the injured brain. These tools are useful for follow-up evaluation of secondary postinjury pathologies. PMID- 27199362 TI - 124I PET Assessment of Response of Bone Metastases to Initial Radioiodine Treatment of Differentiated Thyroid Cancer. AB - : Iodine-positive bone metastases (BMs) are often resistant after initial radioiodine therapy applying the standard-activity approach. A comprehensive lesion-based response study for BMs has not, to our knowledge, yet been performed. In this study, pretherapy and follow-up 124I PET/CT data on BMs from differentiated thyroid cancer patients were retrospectively analyzed to assess the relationship between absorbed dose (AD) of radiation and response after initial radioiodine treatment. METHODS: Before and after initial radioiodine therapy, patients underwent serial PET/CT scanning after administration of 20-40 MBq of 124I. The pretherapy PET data were used to segment BM volumes and to predict the average ADs after administration of dosimetry-guided 131I activity. The lower volume limit of determinability of the applied segmentation method was a sphere volume of 0.16 mL. This volume limit classified the BMs into known volume and fixed-volume groups with their respective average and minimum ADs. Follow-up 124I and 18F-FDG PET/CT data after treatment were analyzed to assess lesion-based therapy response. Response rates at different AD thresholds were calculated and were expressed as the percentage of completely responding BMs above the respective AD threshold. BMs with a maximum extent greater than twice the PET spatial resolution were visually scored for nonuniformity. RESULTS: In total, 61 BMs in 10 patients were included, of which 46 and 15 comprised the known-volume group and the fixed-volume group, respectively. The median follow-up time was 5.6 mo (range, 3.7-23.2 mo). The median average and median minimum ADs in therapy were 183 Gy (range, 39-3,600 Gy) and 270 Gy (range, 63-1,300 Gy), respectively. A range of response rate of 70%-80% was achieved at an AD threshold range of 350-650 Gy. There were 26 BMs that were amenable to visual assessment of nonuniformity, of which two thirds (17/26) were scored as clearly nonuniform, and the majority (11/17) of these nonuniform BMs responded incompletely. CONCLUSION: Both the high AD threshold associated with high response rates and the low median AD per unit of 131I activity elucidate the difficulty in achieving therapeutic efficacy for BMs when a single standard activity is administered. The relatively high AD threshold range is possibly a result of distinct levels of spatial nonuniformity in ADs. PMID- 27199363 TI - Dual-Modality Activity-Based Probes as Molecular Imaging Agents for Vascular Inflammation. AB - : Macrophages are cellular mediators of vascular inflammation and are involved in the formation of atherosclerotic plaques. These immune cells secrete proteases such as matrix metalloproteinases and cathepsins that contribute to disease formation and progression. Here, we demonstrate that activity-based probes (ABPs) targeting cysteine cathepsins can be used in murine models of atherosclerosis to noninvasively image activated macrophage populations using both optical and PET/CT methods. The probes can also be used to topically label human carotid plaques demonstrating similar specific labeling of activated macrophage populations. METHODS: Macrophage-rich carotid lesions were induced in FVB mice fed on a high-fat diet by streptozotocin injection followed by ligation of the left common carotid artery. Mice with carotid atherosclerotic plaques were injected with the optical or dual-modality probes BMV109 and BMV101, respectively, via the tail vein and noninvasively imaged by optical and small animal PET/CT at different time points. After noninvasive imaging, the murine carotid arteries were imaged in situ and ex vivo, followed by immunofluorescence staining to confirm target labeling. Additionally, human carotid plaques were topically labeled with the probe and analyzed by both sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunofluorescence staining to confirm the primary targets of the probe. RESULTS: Quantitative analysis of the signal intensity from both optical and PET/CT imaging showed significantly higher levels of accumulation of BMV109 and BMV101 (P < 0.005 and P < 0.05, respectively) in the ligated left carotid arteries than the right carotid or healthy arteries. Immunofluorescence staining for macrophages in cross-sectional slices of the murine artery demonstrated substantial infiltration of macrophages in the neointima and adventitia of the ligated left carotid arteries compared with the right. Analysis of the human plaque tissues by sodium dodecyl sulfate polyacrylamide gel electrophoresis confirmed that the primary targets of the probe were cathepsins X, B, S, and L. Immunofluorescence labeling of the human tissue with the probe demonstrated colocalization of the probe with CD68, elastin, and cathepsin S, similar to that observed in the experimental carotid inflammation murine model. CONCLUSION: We demonstrate that ABPs targeting the cysteine cathepsins can be used in murine models of atherosclerosis to noninvasively image activated macrophage populations using both optical and PET/CT methods. The probes could also be used to topically label human carotid plaques demonstrating similar specific labeling of activated macrophage populations. Therefore, ABPs targeting the cysteine cathepsins are potentially valuable new reagents for rapid and noninvasive imaging of atherosclerotic disease progression and plaque vulnerability. PMID- 27199365 TI - Characterization of 18F-FPyKYNE-Losartan for Imaging AT1 Receptors. AB - : Most physiologic effects of the renin angiotensin system (RAS) are mediated via the angiotensin (Ang) type 1 receptor (AT1R). The 18F-FPyKYNE derivative of the clinically used AT1R blocker losartan exhibits high binding selectivity for kidney AT1R and rapid metabolism in rats. The aim of this study was to further assess the binding profile of this novel PET agent for imaging AT1R in rats and pigs. METHODS: In vitro binding assays were performed with 18F-FPyKYNE-losartan in rat kidneys. Male Sprague-Dawley rats were used to assess dosimetry, antagonistic efficacy via blood pressure measurements, and presence of labeled metabolites in kidneys. Test-retest PET imaging, blocking with AT1R antagonist candesartan (10 mg/kg), and plasma metabolism analysis were performed in female Yorkshire pigs. RESULTS: 18F-FPyKYNE-losartan bound with high affinity (dissociation constant of 49.4 +/- 18.0 nM and maximal binding of 348 +/- 112 fmol/mm2) to rat kidney AT1R. It bound strongly to plasma proteins in rats (97%), and its labeled metabolites displayed minimal interference on renal AT1R binding. FPyKYNE-losartan fully antagonized the Ang II pressor effect, albeit with 4-fold potency reduction (the effective dose inhibiting 50% of the Ang II-induced maximal pressor response of 25.5 mg/kg) relative to losartan. PET imaging exhibited high kidney-to-blood contrast and slow renal clearance, with an SUV of 14.1 +/- 6.2. Excellent reproducibility was observed in the calculated test retest variability (7.2% +/- 0.75%). Only hydrophilic-labeled metabolites were present in plasma samples, and renal retention was reduced (-60%) at 10-15 min after blockade with candesartan. CONCLUSION: 18F-FPyKYNE-losartan has a favorable binding profile and displays high potential for translational work in humans as an AT1R PET imaging agent. PMID- 27199364 TI - Preclinical Evaluation of a P2X7 Receptor-Selective Radiotracer: PET Studies in a Rat Model with Local Overexpression of the Human P2X7 Receptor and in Nonhuman Primates. AB - The P2X7 receptor (P2X7R) orchestrates neuroinflammation, and this is the basis for an increased interest in the development of antagonists inhibiting P2X7R function in the brain. This study provides the preclinical evaluation of (11)C JNJ-54173717, a PET tracer for P2X7R in both rats and nonhuman primates. METHODS: (11)C-JNJ-54173717 is a high-affinity radiotracer for the human P2X7R (hP2X7R). Biodistribution and radiometabolite studies were performed. Viral vectors encoding either enhanced green fluorescent protein-hP2X7R or 3flag-hP2X7R were engineered and validated in cell culture. hP2X7R was regionally overexpressed in the rat striatum after stereotactic injection of viral vectors. Dynamic small animal PET studies were performed in vector-injected rats and in healthy monkeys using (11)C-JNJ-54173717. RESULTS: The affinity of JNJ-54173717 was 1.6 +/- 0.1 nM in a rat cortex P2X7R membrane binding assay. In a functional assay at the recombinant human and rat P2X7R orthologs, the half maximal inhibitory concentration (IC50) of JNJ-54173717 was 4.2 +/- 0.01 nM and 7.6 +/- 0.01 nM, respectively. The rat biodistribution study showed that (11)C-JNJ-54173717 crossed the blood-brain barrier and was cleared from plasma mainly via the hepatobiliary pathway. A polar radiometabolite was found in rat plasma. No radiometabolites were detected in rat brain. Dynamic small-animal PET showed binding of (11)C-JNJ-54173717 in the striatum expressing hP2X7R, with rapid washout from the noninjected control striatum and other brain regions. Likewise, (11)C-JNJ-54173717 PET signal was blocked by a chemically distinct P2X7R ligand, indicating specific binding to P2X7R in the monkey brain. CONCLUSION: JNJ 54173717 is a high-affinity P2X7R antagonist. An animal rat model stably expressing hP2X7R was developed and validated, identifying favorable characteristics for (11)C-JNJ-54173717 as a PET radioligand for in vivo visualization of hP2X7R. (11)C-JNJ-54173717 selectively visualized P2X7R in the monkey brain, and this radioligand will be further evaluated in a clinical setting to study P2X7R expression levels in neurodegenerative disorders. PMID- 27199371 TI - Applied stretch initiates directional invasion through the action of Rap1 GTPase as a tension sensor. AB - Although it is known that a stiffening of the stroma and the rearrangement of collagen fibers within the extracellular matrix facilitate the movement of tumor cells away from the primary lesion, the underlying mechanisms responsible are not fully understood. We now show that this invasion, which can be initiated by applying tensional loads to a three-dimensional collagen gel matrix in culture, is dependent on the Rap1 GTPases (Rap1a and Rap1b, referred to collectively as Rap1). Under these conditions Rap1 activity stimulates the formation of focal adhesion structures that align with the tensional axis as single tumor cells move into the matrix. These effects are mediated by the ability of Rap1 to induce the polarized polymerization and retrograde flow of actin, which stabilizes integrins and recruits vinculin to preformed adhesions, particularly those near the leading edge of invasive cells. Rap1 activity also contributes to the tension-induced collective invasive elongation of tumor cell clusters and it enhances tumor cell growth in vivo Thus, Rap1 mediates the effects of increased extracellular tension in multiple ways that are capable of contributing to tumor progression when dysregulated. PMID- 27199372 TI - DeepCAGE transcriptomics identify HOXD10 as a transcription factor regulating lymphatic endothelial responses to VEGF-C. AB - Lymphangiogenesis plays a crucial role during development, in cancer metastasis and in inflammation. Activation of VEGFR-3 (also known as FLT4) by VEGF-C is one of the main drivers of lymphangiogenesis, but the transcriptional events downstream of VEGFR-3 activation are largely unknown. Recently, we identified a wave of immediate early transcription factors that are upregulated in human lymphatic endothelial cells (LECs) within the first 30 to 80 min after VEGFR-3 activation. Expression of these transcription factors must be regulated by additional pre-existing transcription factors that are rapidly activated by VEGFR 3 signaling. Using transcription factor activity analysis, we identified the homeobox transcription factor HOXD10 to be specifically activated at early time points after VEGFR-3 stimulation, and to regulate expression of immediate early transcription factors, including NR4A1. Gain- and loss-of-function studies revealed that HOXD10 is involved in LECs migration and formation of cord-like structures. Furthermore, HOXD10 regulates expression of VE-cadherin, claudin-5 and NOS3 (also known as e-NOS), and promotes lymphatic endothelial permeability. Taken together, these results reveal an important and unanticipated role of HOXD10 in the regulation of VEGFR-3 signaling in lymphatic endothelial cells, and in the control of lymphangiogenesis and permeability. PMID- 27199374 TI - Genetic risk variants for autoimmune diseases that influence gene expression in thymus. AB - Genome-wide association studies (GWAS) have boosted our knowledge of genetic risk variants in autoimmune diseases (AIDs). Most risk variants are located within or near genes with immunological functions, and the majority is found to be non coding, pointing towards a regulatory role. In this study, we performed a cis expression quantitative trait locus (eQTL) screen restricted to 353 AID associated risk variants selected from the GWAS catalog to investigate whether these single nucleotide polymorphisms (SNPs) influence gene expression in thymus. Genotypes were obtained by Immunochip (Ichip) and tested against expression of surrounding genes (+/-1 Mb) in human thymic tissue (n = 42). We identified eight significant eQTLs located within seven genetic regions (FCRL3, RNASET2, C2orf74, NPIPB8, SIRPG, SYS1 and AJ006998.2) where the expression was associated with AID risk SNPs at a study-wide level of significance (P < 2.7 * 10-5). In NPIPB8 and AJ006998.2, the eQTL signals appeared to be thymus-specific. Furthermore, many AID risk SNPs from GWAS have been subsequently fine-mapped in recent Ichip projects, and fine-mapped AID SNPs overlapped with the thymic eQTLs within RNASET2 and SIRPG Finally, in all the eQTL regions, except C2orf74, SNPs underlying the thymic eQTLs were predicted to interfere with transcription factors important in T cell development. Our study therefore reveals autoimmune risk variants that act as eQTLs in thymus, and suggest that thymic gene regulation may play a functional role at some AID risk loci. PMID- 27199375 TI - A Practical Guide to Writing and Reviewing Abstracts for Pediatric Academic Meetings. PMID- 27199373 TI - Meiotic onset is reliant on spatial distribution but independent of germ cell number in the mouse ovary. AB - Mouse ovarian germ cells enter meiosis in a wave that propagates from anterior to posterior, but little is known about contribution of germ cells to initiation or propagation of meiosis. In a Ror2 mutant with diminished germ cell number and migration, we find that overall timing of meiotic initiation is delayed at the population level. We use chemotherapeutic depletion to exclude a profoundly reduced number of germ cells as a cause for meiotic delay. We rule out sex reversal or failure to specify somatic support cells as contributors to the meiotic phenotype. Instead, we find that anomalies in the distribution of germ cells as well as gonad shape in mutants contribute to aberrant initiation of meiosis. Our analysis supports a model of meiotic initiation via diffusible signal(s), excludes a role for germ cells in commencing the meiotic wave and furnishes the first phenotypic demonstration of the wave of meiotic entry. Finally, our studies underscore the importance of considering germ cell migration defects while studying meiosis to discern secondary effects resulting from positioning versus primary meiotic entry phenotypes. PMID- 27199379 TI - Catastrophes during video-assisted thoracoscopic thymus surgery for myasthenia gravis. AB - OBJECTIVES: Several series have demonstrated that video-assisted thoracoscopic (VAT) thymectomy is feasible and safe. However, VAT thymectomy is an operation that could invite catastrophes, such as major vascular injuries. We aimed to analyse the events and define the management and outcomes of these serious complications. METHODS: All patients who underwent VAT thymectomy/thymothymectomy recorded in our clinical database were evaluated. A catastrophic complication was defined as any situation that resulted in an additional unplanned major surgical procedure other than the planned closed thymic surgery. Operations were performed by two surgeons: one experienced and one junior. The order of catastrophes in each surgeon's experience was recorded. RESULTS: A total of 441 VAT thymectomy/thymothymectomy operations were performed. Catastrophic complications were identified in 7 (1.5%) patients. These cases included 3 major innominate vein injuries, 1 superior vena cava injury, 1 aortic injury, 1 sudden cardiac arrest and 1 diaphragmatic injury. The first catastrophe for the experienced surgeon was his 96th case. The mean age was 37.1 +/- 11.5 (minimum: 21, maximum: 53). There were 5 (71.4%) male and 2 (28.6%) female patients. Two (28.6%) of the patients had thymoma and the mean body mass index was 23.9 +/- 2.8. A mean of 1.7 +/- 1.4 (minimum: 0, maximum: 3) units of blood were transfused; a postoperative intensive care unit stay of 20.6 +/- 25.7 h and a hospital stay of 8.4 +/- 7.9 days were recorded. There were no deaths. CONCLUSIONS: Catastrophic intraoperative complications of VAT thymectomy are very rare. They may not only occur in the learning curve period but also after a large experience. Experience in converting to open surgery within seconds is important to reduce morbidity and mortality. PMID- 27199380 TI - Effect of negative pressure wound therapy followed by tissue flaps for deep sternal wound infection after cardiovascular surgery: propensity score matching analysis. AB - OBJECTIVES: Deep sternal wound infection (DSWI) after cardiovascular surgery via median sternotomy remains a severe complication associated with a drastic decrease in the quality of life. We assessed the risk factors for in-hospital death caused by DSWI and the available treatments for DSWI. METHODS: Between January 1991 and August 2015, we retrospectively reviewed 73 patients (51 males and 22 females, mean age 67.5 +/- 10.3 years) who developed DSWI after cardiovascular surgery via median sternotomy. Pathogenic bacteria mainly comprised methicillin-resistant Staphylococcus aureus (MRSA) (49.3%). Fifteen patients (20.5%) died in hospital with DSWI. Treatment of DSWI consisted of open daily irrigation (up to 2006) or negative pressure wound therapy (NPWT) (2007 onwards), followed by primary closure or reconstruction of tissue flaps. We assessed the risk factors for in-hospital mortality from DSWI by comparing data from the 15 patients who died and the 58 survivors using propensity score matching analysis of the treatments used for DSWI. RESULTS: Univariate analysis identified age, use of intra-aortic balloon pumping, prolonged mechanical ventilation, tracheotomy, prolonged intensive care unit stay, postoperative low output syndrome, postoperative myocardial infarction, postoperative renal failure, postoperative use of haemodialysis, postoperative pneumonia, postoperative cerebral disorder, MRSA infection, NPWT and tissue flaps as being associated with in-hospital mortality (P < 0.05). Multivariate analysis identified NPWT (odds ratio, 0.062; 95% confidence interval, 0.004-0.897; P = 0.041) and tissue flaps (odds ratio, 0.022; 95% confidence interval, 0.000-0.960; P = 0.048) as independently associated with reduced in-hospital mortality after DSWI. On comparing 22 patients receiving NPWT with 22 not on NPWT using propensity score matching, patients on NPWT had significantly lower in-hospital mortality than those without NPWT (NPWT vs non-NPWT, 5 vs 36%, P = 0.021). In DSWI infected by MRSA, NPWT significantly reduced the in-hospital mortality caused by DSWI (NPWT vs non-NPWT, 0 vs 52%, P = 0.003). CONCLUSIONS: NPWT and tissue flaps may be favourable factors associated with reduced in-hospital mortality attributable to DSWI. NPWT as a bridge therapy to tissue flaps may play a major role in treating DSWI and improve the prognosis for patients with MRSA infected DSWI. PMID- 27199382 TI - The application of susceptibility-weighted MRI in pre-interventional evaluation of intracranial dural arteriovenous fistulas. AB - BACKGROUND AND PURPOSE: Detection and characterization of intracranial dural arteriovenous fistula (DAVF) is important to plan appropriate therapeutic management. The aim of this study was to analyze the utility of susceptibility weighted MRI (SWI) in the pre-therapeutic assessment of DAVF in comparison with gold standard digital subtraction angiography (DSA). MATERIALS AND METHODS: Prospectively, 26 patients with DAVFs underwent a thorough clinical examination and MRI including SWI followed by cerebral DSA. Two observers blinded to the DSA findings evaluated conventional MRI and SWI images and identified the fistulous area (FA), cortical venous reflux (CVR), and cortical venous ectasia (CVE) and compared these observations with the DSA findings documented by a third observer. RESULTS: Aggressive clinical symptoms were observed in 31% of patients and benign features were noted in 69% of DAVFs. Conventional MRI could identify the FA in only 27% of patients. SWI accurately located 75% of all the FAs in 23 patients. However, SWI failed to identify DAVFs in three patients. CVR was detected in 89.6% of all aggressive DAVFs. The accuracy of SWI to identify CVE was 100% and the extent and degree correlated with DSA observations. CONCLUSIONS: SWI is a reliable non-invasive tool for the localization and characterization of DAVFs and is superior to conventional MRI in the evaluation of DAVFs. This sequence can demonstrate underlying cerebral hemodynamic stresses with a high degree of accuracy and provide valuable pre-therapeutic information. PMID- 27199381 TI - Tracheal rupture after intubation and placement of an endotracheal balloon catheter (A-view(r)) in cardiac surgery. AB - The endotracheal balloon catheter (A-view(r)) is a device developed to locate atherosclerotic plaques of the ascending aorta (AA) in cardiac surgery to prevent stroke. The saline-filled balloon is located in the trachea and combines the advantages of transoesophageal echocardiography (e.g. used before performing the sternotomy) and intraoperative epiaortic ultrasound scanning (e.g. complete view of the AA). We report the first severe complication after the use of A-view(r). This is a case of a 66-year old woman who underwent elective myocardial revascularization complicated by an intraoperative iatrogenic tracheal rupture of 6 cm, after uncomplicated intubation and the use of an endotracheal balloon catheter (A-view(r)), which required direct surgical repair with a posterolateral thoracotomy after the myocardial revascularization was completed, weaning from bypass and closure of the median sternotomy. PMID- 27199383 TI - Venous sinus stenting in patients without idiopathic intracranial hypertension. AB - BACKGROUND: Venous sinus stenting is an effective treatment for patients with idiopathic intracranial hypertension (IIH) and venous sinus stenosis. OBJECTIVE: To determine the usefulness of venous sinus stenting in the treatment of patients with symptomatic venous sinus stenosis without a diagnosis of IIH. METHODS: We performed a retrospective review of a prospective multicenter database of patients undergoing venous sinus stenting between January 2008 and February 2016. Patients with acute dural venous sinus thrombosis, arteriovenous fistula or arteriovenous malformation, or IIH were excluded. Clinical, radiological, and ophthalmological information was recorded. RESULTS: Nine patients met the inclusion criteria and underwent venous sinus stenting for symptomatic dural venous sinus stenosis. Reasons for treatment included isolated unilateral pulsatile tinnitus (n=1), congenital hydrocephalus (n=2), unilateral pulsatile tinnitus following prior venous sinus thrombosis (n=1), acquired hydrocephalus following dural sinus thrombosis (n=2), meningitis (n=2) and tumor invasion into the dural venous sinus (n=1). Six patients underwent lumbar puncture or shunt tap, and all of these patients had elevated intracranial pressure. All stenoses were located in the transverse sinus, transverse-sigmoid junction and/or jugular bulb, and all were treated with self-expanding bare-metal stents. At follow-up, clinical symptoms had resolved in all but two patients, both of whom had congenital hydrocephalus and pre-existing shunts. There was no significant in stent stenosis, and patients with ophthalmological follow-up demonstrated improvement of papilledema. CONCLUSIONS: Dural venous sinus stenting may be an effective treatment for patients with symptomatic venous sinus stenosis without IIH in carefully selected cases, but may not be effective in resolving the symptoms of congenital hydrocephalus. PMID- 27199384 TI - Endovascular thrombectomy in the setting of aortic dissection. AB - BACKGROUND: Recent studies have validated the use of endovascular thrombectomy in large vessel ischemic stroke provided patients are selected appropriately. However, to our knowledge, there have been no previously reported cases of endovascular thrombectomy in patients with aortic dissection. We report three such cases, two with chronic aortic dissections (including one with a history of Marfan syndrome) and another with an acute type B dissection. METHODS: Case studies and review of relevant literature. RESULTS: Three patients with a history of aortic dissection presented with acute onset right middle cerebral artery syndromes, two of whom had chronic aortic dissections that were status-post graft repair, while a third had an acute type B aortic dissection that had been managed with a femoral-to-femoral bypass. None of the three were candidates for intravenous tissue plasminogen activator. All three were found to have proximal right M1 occlusions on non-invasive imaging and were taken for endovascular thrombectomy via transfemoral, transradial, and transbrachial approaches, respectively. All three had successful recanalization (with Thrombolysis In Cerebral Infarction (TICI) 2b, TICI 3, and TICI 2b flow, respectively) along with clinical improvement, and none had procedure-related complications. CONCLUSIONS: These three cases suggest that endovascular thrombectomy is feasible and can be done safely and efficaciously in patients with aortic dissections and those with Marfan syndrome, although the risks and benefits should be considered as part of any decision-making process. Given that endovascular therapy for acute stroke is now in many situations part of standard care, further studies will be necessary to delineate more precise inclusion and exclusion criteria. PMID- 27199386 TI - Letter to the editor: "Doxorubicin and ErbB2 overexpression: another piece in the mitochondrial jigsaw". PMID- 27199387 TI - Scenario Analysis for Programmatic Tuberculosis Control in Western Province, Papua New Guinea. AB - Tuberculosis (TB) and multidrug-resistant TB (MDR-TB) are major health problems in Western Province, Papua New Guinea. While comprehensive expansion of TB control programs is desirable, logistical challenges are considerable, and there is substantial uncertainty regarding the true disease burden. We parameterized our previously described mathematical model of Mycobacterium tuberculosis dynamics in Western Province, following an epidemiologic assessment. Five hypothetical scenarios representing alternative programmatic approaches during the period from 2013 to 2023 were developed with local staff. Bayesian uncertainty analyses were undertaken to explicitly acknowledge the uncertainty around key epidemiologic parameters, and an economic evaluation was performed. With continuation of existing programmatic strategies, overall TB incidence remained stable at 555 cases per 100,000 population per year (95% simulation interval (SI): 420, 807), but the proportion of incident cases attributable to MDR-TB increased from 16% to 35%. Comprehensive, provincewide strengthening of existing programs reduced incidence to 353 cases per 100,000 population per year (95% SI: 246, 558), with 46% being cases of MDR-TB, while incorporating programmatic management of MDR-TB into these programs reduced incidence to 233 cases per 100,000 population per year (95% SI: 198, 269) with 14% MDR-TB. Most economic costs were due to hospitalization during the intensive treatment phase. Broad scale-up of TB control activities in Western Province with incorporation of programmatic management of MDR-TB is vital if control is to be achieved. Community-based treatment approaches are important to reduce the associated economic costs. PMID- 27199388 TI - Efficacy of Vinblastine and Prednisone in Multicentric Reticulohistiocytosis With Onset in Infancy. AB - Multicentric reticulohistiocytosis (MRH) is a rare histiocytic proliferative disorder of uncertain etiology, characterized by mucocutaneous papulonodular lesions and progressive, symmetric erosive arthritis. MRH can coexist with various autoimmune disorders, tuberculosis, and malignancy. It usually occurs in the elderly and is very rare in children. This is probably the first case in which disease manifestation appeared in infancy in the form of skin lesions. The patient had recurrent ulceration of cutaneous lesions, which is unusual in MRH. Early diagnosis and aggressive treatment are essential to prevent progressive irreversible course and development of arthritis mutilans. Various drugs, such as steroids, nonsteroidal anti-inflammatory drugs, immunosuppressants, interleukin inhibitors, and tumor necrosis factor-alpha antagonist, have been tried with variable responses. The present case responded well to vinblastine and steroid, which have not been reported previously. Here, we document a case of MRH with early onset in infancy along with role of vinblastine and prednisone in its treatment. PMID- 27199389 TI - A Call for Fertility and Sexual Function Counseling in Pediatrics. PMID- 27199390 TI - Leave no city behind. PMID- 27199392 TI - HUMAN EVOLUTION. Tracking how humans evolve in real time. PMID- 27199393 TI - IMAGING. 'Cell painting' highlights responses to drugs and toxins. PMID- 27199394 TI - HUMAN SUBJECTS. Researchers decry consent proposal. PMID- 27199396 TI - BEHIND THE NUMBERS. 'Employment crisis' for new Ph.D.s is an illusion. PMID- 27199395 TI - ORGANIC CHEMISTRY. A modular route to new antibiotics. PMID- 27199385 TI - The Association of Cigarette Smoking With Depression and Anxiety: A Systematic Review. AB - BACKGROUND: Many studies report a positive association between smoking and mental illness. However, the literature remains mixed regarding the direction of this association. We therefore conducted a systematic review evaluating the association of smoking and depression and/or anxiety in longitudinal studies. METHODS: Studies were identified by searching PubMed, Scopus, and Web of Science and were included if they: (1) used human participants, (2) were longitudinal, (3) reported primary data, (4) had smoking as an exposure and depression and/or anxiety as an outcome, or (5) had depression and/or anxiety as the exposure and smoking as an outcome. RESULTS: Outcomes from 148 studies were categorized into: smoking onset, smoking status, smoking heaviness, tobacco dependence, and smoking trajectory. The results for each category varied substantially, with evidence for positive associations in both directions (smoking to later mental health and mental health to later smoking) as well as null findings. Overall, nearly half the studies reported that baseline depression/anxiety was associated with some type of later smoking behavior, while over a third found evidence that a smoking exposure was associated with later depression/anxiety. However, there were few studies directly supporting a bidirectional model of smoking and anxiety, and very few studies reporting null results. CONCLUSIONS: The literature on the prospective association between smoking and depression and anxiety is inconsistent in terms of the direction of association most strongly supported. This suggests the need for future studies that employ different methodologies, such as Mendelian randomization (MR), which will allow us to draw stronger causal inferences. IMPLICATIONS: We systematically reviewed longitudinal studies on the association of different aspects of smoking behavior with depression and anxiety. The results varied considerably, with evidence for smoking both associated with subsequent depression and anxiety, and vice versa. Few studies supported a bidirectional relationship, or reported null results, and no clear patterns by gender, ethnicity, clinical status, length to follow-up, or diagnostic test. Suggesting that despite advantages of longitudinal studies, they cannot alone provide strong evidence of causality. Therefore, future studies investigating this association should employ different methods allowing for stronger causal inferences to be made, such as MR. PMID- 27199397 TI - NEUROSCIENCE. Can brain scans reveal concussion-linked disease? PMID- 27199398 TI - The Truest Test. PMID- 27199400 TI - NANOTECHNOLOGY. Changing of the guard. PMID- 27199401 TI - PHYSICS. Superconductivity on the edge. PMID- 27199402 TI - BIOCHEMISTRY. Methane--make it or break it. PMID- 27199403 TI - CELL BIOLOGY. Formin' filaments at a faster CLIP. PMID- 27199404 TI - ROBOTICS. Learning from nature how to land aerial robots. PMID- 27199405 TI - INTERNATIONAL MIGRATION. International migration under the microscope. PMID- 27199407 TI - Cities are the Future. PMID- 27199408 TI - Rise of the City. PMID- 27199406 TI - SCIENTIFIC COMMUNITY. Preprints for the life sciences. PMID- 27199409 TI - Roots of the Urban Mind. PMID- 27199411 TI - China Rethinks Cities. PMID- 27199410 TI - A Plague of Rats. PMID- 27199412 TI - Vancouver's Green Dream. PMID- 27199413 TI - City-integrated renewable energy for urban sustainability. AB - To prepare for an urban influx of 2.5 billion people by 2050, it is critical to create cities that are low-carbon, resilient, and livable. Cities not only contribute to global climate change by emitting the majority of anthropogenic greenhouse gases but also are particularly vulnerable to the effects of climate change and extreme weather. We explore options for establishing sustainable energy systems by reducing energy consumption, particularly in the buildings and transportation sectors, and providing robust, decentralized, and renewable energy sources. Through technical advancements in power density, city-integrated renewable energy will be better suited to satisfy the high-energy demands of growing urban areas. Several economic, technical, behavioral, and political challenges need to be overcome for innovation to improve urban sustainability. PMID- 27199414 TI - Emerging solutions to the water challenges of an urbanizing world. AB - The top priorities for urban water sustainability include the provision of safe drinking water, wastewater handling for public health, and protection against flooding. However, rapidly aging infrastructure, population growth, and increasing urbanization call into question current urban water management strategies, especially in the fast-growing urban areas in Asia and Africa. We review innovative approaches in urban water management with the potential to provide locally adapted, resource-efficient alternative solutions. Promising examples include new concepts for stormwater drainage, increased water productivity, distributed or on-site treatment of wastewater, source separation of human waste, and institutional and organizational reforms. We conclude that there is an urgent need for major transdisciplinary efforts in research, policy, and practice to develop alternatives with implications for cities and aquatic ecosystems alike. PMID- 27199415 TI - Transport solutions for cleaner air. AB - In cities across the globe, road transport remains an important source of air pollutants that are linked with acute and chronic health effects. Decreasing vehicle emissions--while maintaining or increasing commuter journeys--remains a major challenge for city administrators. In London, congestion-charging and a citywide low-emission zone failed to bring nitrogen dioxide concentrations under control. In Beijing, controls on the purchase and use of cars have not decreased transport emissions to a sufficient extent. As cities continue to grow, not even zero-emission vehicles are the solution. Moving increasingly large numbers of people efficiently around a city can only be achieved by expanding mass transit systems. PMID- 27199416 TI - The ecological future of cities. AB - The discipline of urban ecology arose in the 1990s, primarily motivated by a widespread interest in documenting the distribution and abundance of animals and plants in cities. Today, urban ecologists have greatly expanded their scope of study to include ecological and socioeconomic processes, urban management, planning, and design, with the goal of addressing issues of sustainability, environmental quality, and human well-being within cities and towns. As the global pace of urbanization continues to intensify, urban ecology provides the ecological and social data, as well as the principles, concepts and tools, to create livable cities. PMID- 27199417 TI - Living in cities, naturally. AB - Natural features, settings, and processes in urban areas can help to reduce stress associated with urban life. In this and other ways, public health benefits from, street trees, green roofs, community gardens, parks and open spaces, and extensive connective pathways for walking and biking. Such urban design provisions can also yield ecological benefits, not only directly but also through the role they play in shaping attitudes toward the environment and environmental protection. Knowledge of the psychological benefits of nature experience supports efforts to better integrate nature into the architecture, infrastructure, and public spaces of urban areas. PMID- 27199418 TI - Meta-principles for developing smart, sustainable, and healthy cities. AB - Policy directives in several nations are focusing on the development of smart cities, linking innovations in the data sciences with the goal of advancing human well-being and sustainability on a highly urbanized planet. To achieve this goal, smart initiatives must move beyond city-level data to a higher-order understanding of cities as transboundary, multisectoral, multiscalar, social ecological-infrastructural systems with diverse actors, priorities, and solutions. We identify five key dimensions of cities and present eight principles to focus attention on the systems-level decisions that society faces to transition toward a smart, sustainable, and healthy urban future. PMID- 27199419 TI - Hidden linkages between urbanization and food systems. AB - Global societies are becoming increasingly urban. This shift toward urban living is changing our relationship with food, including how we shop and what we buy, as well as ideas about sanitation and freshness. Achieving food security in an era of rapid urbanization will require considerably more understanding about how urban and food systems are intertwined. Here we discuss some potential understudied linkages that are ripe for further examination. PMID- 27199420 TI - Building functional cities. AB - The literature views many African cities as dysfunctional with a hodgepodge of land uses and poor "connectivity." One driver of inefficient land uses is construction decisions for highly durable buildings made under weak institutions. In a novel approach, we model the dynamics of urban land use with both formal and slum dwellings and ongoing urban redevelopment to higher building heights in the formal sector as a city grows. We analyze the evolution of Nairobi using a unique high-spatial resolution data set. The analysis suggests insufficient building volume through most of the city and large slum areas with low housing volumes near the center, where corrupted institutions deter conversion to formal sector usage. PMID- 27199421 TI - The radical mechanism of biological methane synthesis by methyl-coenzyme M reductase. AB - Methyl-coenzyme M reductase, the rate-limiting enzyme in methanogenesis and anaerobic methane oxidation, is responsible for the biological production of more than 1 billion tons of methane per year. The mechanism of methane synthesis is thought to involve either methyl-nickel(III) or methyl radical/Ni(II)-thiolate intermediates. We employed transient kinetic, spectroscopic, and computational approaches to study the reaction between the active Ni(I) enzyme and substrates. Consistent with the methyl radical-based mechanism, there was no evidence for a methyl-Ni(III) species; furthermore, magnetic circular dichroism spectroscopy identified the Ni(II)-thiolate intermediate. Temperature-dependent transient kinetics also closely matched density functional theory predictions of the methyl radical mechanism. Identifying the key intermediate in methanogenesis provides fundamental insights to develop better catalysts for producing and activating an important fuel and potent greenhouse gas. PMID- 27199422 TI - Ubiquitous signatures of nematic quantum criticality in optimally doped Fe-based superconductors. AB - A key actor in the conventional theory of superconductivity is the induced interaction between electrons mediated by the exchange of virtual collective fluctuations (phonons in the case of conventional s-wave superconductors). Other collective modes that can play the same role, especially spin fluctuations, have been widely discussed in the context of high-temperature and heavy Fermion superconductors. The strength of such collective fluctuations is measured by the associated susceptibility. Here we use differential elastoresistance measurements from five optimally doped iron-based superconductors to show that divergent nematic susceptibility appears to be a generic feature in the optimal doping regime of these materials. This observation motivates consideration of the effects of nematic fluctuations on the superconducting pairing interaction in this family of compounds and possibly beyond. PMID- 27199423 TI - Rewritable artificial magnetic charge ice. AB - Artificial ices enable the study of geometrical frustration by design and through direct observation. However, it has proven difficult to achieve tailored long range ordering of their diverse configurations, limiting both fundamental and applied research directions. We designed an artificial spin structure that produces a magnetic charge ice with tunable long-range ordering of eight different configurations. We also developed a technique to precisely manipulate the local magnetic charge states and demonstrate write-read-erase multifunctionality at room temperature. This globally reconfigurable and locally writable magnetic charge ice could provide a setting for designing magnetic monopole defects, tailoring magnonics, and controlling the properties of other two-dimensional materials. PMID- 27199424 TI - Supercurrent in the quantum Hall regime. AB - A promising route for creating topological states and excitations is to combine superconductivity and the quantum Hall (QH) effect. Despite this potential, signatures of superconductivity in the QH regime remain scarce, and a superconducting current through a QH weak link has been challenging to observe. We demonstrate the existence of a distinct supercurrent mechanism in encapsulated graphene samples contacted by superconducting electrodes, in magnetic fields as high as 2 tesla. The observation of a supercurrent in the QH regime marks an important step in the quest for exotic topological excitations, such as Majorana fermions and parafermions, which may find applications in fault-tolerant quantum computing. PMID- 27199425 TI - Quantifying the promotion of Cu catalysts by ZnO for methanol synthesis. AB - Promoter elements enhance the activity and selectivity of heterogeneous catalysts. Here, we show how methanol synthesis from synthesis gas over copper (Cu) nanoparticles is boosted by zinc oxide (ZnO) nanoparticles. By combining surface area titration, electron microscopy, activity measurement, density functional theory calculations, and modeling, we show that the promotion is related to Zn atoms migrating in the Cu surface. The Zn coverage is quantitatively described as a function of the methanol synthesis conditions and of the size-dependent thermodynamic activities of the Cu and ZnO nanoparticles. Moreover, experimental data reveal a strong interdependency of the methanol synthesis activity and the Zn coverage. These results demonstrate the size dependent activities of nanoparticles as a general means to design synergetic functionality in binary nanoparticle systems. PMID- 27199426 TI - Self-assembly of noble metal monolayers on transition metal carbide nanoparticle catalysts. AB - We demonstrated the self-assembly of transition metal carbide nanoparticles coated with atomically thin noble metal monolayers by carburizing mixtures of noble metal salts and transition metal oxides encapsulated in removable silica templates. This approach allows for control of the final core-shell architecture, including particle size, monolayer coverage, and heterometallic composition. Carbon-supported Ti(0.1)W(0.9)C nanoparticles coated with Pt or bimetallic PtRu monolayers exhibited enhanced resistance to sintering and CO poisoning, achieving an order of magnitude increase in specific activity over commercial catalysts for methanol electrooxidation after 10,000 cycles. These core-shell materials provide a new direction to reduce the loading, enhance the activity, and increase the stability of noble metal catalysts. PMID- 27199427 TI - Perching and takeoff of a robotic insect on overhangs using switchable electrostatic adhesion. AB - For aerial robots, maintaining a high vantage point for an extended time is crucial in many applications. However, available on-board power and mechanical fatigue constrain their flight time, especially for smaller, battery-powered aircraft. Perching on elevated structures is a biologically inspired approach to overcome these limitations. Previous perching robots have required specific material properties for the landing sites, such as surface asperities for spines, or ferromagnetism. We describe a switchable electroadhesive that enables controlled perching and detachment on nearly any material while requiring approximately three orders of magnitude less power than required to sustain flight. These electroadhesives are designed, characterized, and used to demonstrate a flying robotic insect able to robustly perch on a wide range of materials, including glass, wood, and a natural leaf. PMID- 27199428 TI - ppGpp couples transcription to DNA repair in E. coli. AB - The small molecule alarmone (p)ppGpp mediates bacterial adaptation to nutrient deprivation by altering the initiation properties of RNA polymerase (RNAP). ppGpp is generated in Escherichia coli by two related enzymes, RelA and SpoT. We show that ppGpp is robustly, but transiently, induced in response to DNA damage and is required for efficient nucleotide excision DNA repair (NER). This explains why relA-spoT-deficient cells are sensitive to diverse genotoxic agents and ultraviolet radiation, whereas ppGpp induction renders them more resistant to such challenges. The mechanism of DNA protection by ppGpp involves promotion of UvrD-mediated RNAP backtracking. By rendering RNAP backtracking-prone, ppGpp couples transcription to DNA repair and prompts transitions between repair and recovery states. PMID- 27199430 TI - Enhanced clearance of HIV-1-infected cells by broadly neutralizing antibodies against HIV-1 in vivo. AB - Antiretroviral drugs and antibodies limit HIV-1 infection by interfering with the viral life cycle. In addition, antibodies also have the potential to guide host immune effector cells to kill HIV-1-infected cells. Examination of the kinetics of HIV-1 suppression in infected individuals by passively administered 3BNC117, a broadly neutralizing antibody, suggested that the effects of the antibody are not limited to free viral clearance and blocking new infection but also include acceleration of infected cell clearance. Consistent with these observations, we find that broadly neutralizing antibodies can target CD4(+) T cells infected with patient viruses and can decrease their in vivo half-lives by a mechanism that requires Fcgamma receptor engagement in a humanized mouse model. The results indicate that passive immunotherapy can accelerate elimination of HIV-1-infected cells. PMID- 27199433 TI - A problem by any other name. PMID- 27199431 TI - Accelerated actin filament polymerization from microtubule plus ends. AB - Microtubules (MTs) govern actin network remodeling in a wide range of biological processes, yet the mechanisms underlying this cytoskeletal cross-talk have remained obscure. We used single-molecule fluorescence microscopy to show that the MT plus-end-associated protein CLIP-170 binds tightly to formins to accelerate actin filament elongation. Furthermore, we observed mDia1 dimers and CLIP-170 dimers cotracking growing filament ends for several minutes. CLIP-170 mDia1 complexes promoted actin polymerization ~18 times faster than free-barbed end growth while simultaneously enhancing protection from capping proteins. We used a MT-actin dynamics co-reconstitution system to observe CLIP-170-mDia1 complexes being recruited to growing MT ends by EB1. The complexes triggered rapid growth of actin filaments that remained attached to the MT surface. These activities of CLIP-170 were required in primary neurons for normal dendritic morphology. Thus, our results reveal a cellular mechanism whereby growing MT plus ends direct rapid actin assembly. PMID- 27199429 TI - HIV-1 therapy with monoclonal antibody 3BNC117 elicits host immune responses against HIV-1. AB - 3BNC117 is a broad and potent neutralizing antibody to HIV-1 that targets the CD4 binding site on the viral envelope spike. When administered passively, this antibody can prevent infection in animal models and suppress viremia in HIV-1 infected individuals. Here we report that HIV-1 immunotherapy with a single injection of 3BNC117 affects host antibody responses in viremic individuals. In comparison to untreated controls that showed little change in their neutralizing activity over a 6-month period, 3BNC117 infusion significantly improved neutralizing responses to heterologous tier 2 viruses in nearly all study participants. We conclude that 3BNC117-mediated immunotherapy enhances host humoral immunity to HIV-1. PMID- 27199432 TI - Coregulation of tandem duplicate genes slows evolution of subfunctionalization in mammals. AB - Gene duplication is a fundamental process in genome evolution. However, most young duplicates are degraded by loss-of-function mutations, and the factors that allow some duplicate pairs to survive long-term remain controversial. One class of models to explain duplicate retention invokes sub- or neofunctionalization, whereas others focus on sharing of gene dosage. RNA-sequencing data from 46 human and 26 mouse tissues indicate that subfunctionalization of expression evolves slowly and is rare among duplicates that arose within the placental mammals, possibly because tandem duplicates are coregulated by shared genomic elements. Instead, consistent with the dosage-sharing hypothesis, most young duplicates are down-regulated to match expression levels of single-copy genes. Thus, dosage sharing of expression allows for the initial survival of mammalian duplicates, followed by slower functional adaptation enabling long-term preservation. PMID- 27199434 TI - Erratum for the Research Article "De novo design of protein homo-oligomers with modular hydrogen-bond network-mediated specificity" by S. E. Boyken, Z. Chen, B. Groves, R. A. Langan, G. Oberdorfer, A. Ford, J. M. Gilmore, C. Xu, F. DiMaio, J. Henrique Pereira, B. Sankaran, G. Seelig, P. H. Zwart, D. Baker. PMID- 27199436 TI - A glimpse of Cre-mediated controversies in epicardial signalling. PMID- 27199441 TI - Recurrent spontaneous scleral rupture in Marfan's syndrome. AB - The ocular manifestations of Marfan's syndrome (MS) range from ectopia lentis, microspherophakia, myopia, glaucoma and retinal detachment. Spontaneous scleral rupture is a rare complication and recurrent scleral perforation is extremely rare. We report a rare case of a 26-year-old male with MS who had sequential recurrent spontaneous scleral rupture which required surgical repair. He suffered from a similar problem 4 years later in both eyes in a different location, with overlying thin cystic blebs and hypotony maculopathy. Surgical repair with preserved scleral donor patch graft and conjunctival autograft in one eye, and conjunctival advancement in the other eye was performed. This helped stabilise the eyes, and resulted in complete visual recovery in both eyes. PMID- 27199442 TI - NSAID-induced pyloric stenosis leading to oesophageal intramucosal dissection. AB - We describe a rare case of a 75-year-old woman with significant non-steroidal anti-inflammatory drug (NSAID) use who presented with haematemesis. Upper endoscopy revealed a large (9 cm) intramucosal dissection of the oesophagus without extension into the gastro-oesophageal junction and a severely narrowed pylorus. We postulate that she developed pyloric stenosis due to peptic ulcer disease from chronic NSAID use. This then led to gastro-oesophageal reflux. Undigested pills in the refluxate had contacted oesophageal mucosa, leading to pill-induced oesophageal injury. This, along with vomiting, is postulated to have led to the oesophageal intramucosal dissection. She improved with conservative medical management with a clear liquid diet and proton pump inhibitors, and a follow-up upper endoscopy 1 week later showed recovery of the previously seen intramucosal dissection. PMID- 27199435 TI - The tumor microenvironment underlies acquired resistance to CSF-1R inhibition in gliomas. AB - Macrophages accumulate with glioblastoma multiforme (GBM) progression and can be targeted via inhibition of colony-stimulating factor-1 receptor (CSF-1R) to regress high-grade tumors in animal models of this cancer. However, whether and how resistance emerges in response to sustained CSF-1R blockade is unknown. We show that although overall survival is significantly prolonged, tumors recur in >50% of mice. Gliomas reestablish sensitivity to CSF-1R inhibition upon transplantation, indicating that resistance is tumor microenvironment-driven. Phosphatidylinositol 3-kinase (PI3K) pathway activity was elevated in recurrent GBM, driven by macrophage-derived insulin-like growth factor-1 (IGF-1) and tumor cell IGF-1 receptor (IGF-1R). Combining IGF-1R or PI3K blockade with CSF-1R inhibition in recurrent tumors significantly prolonged overall survival. Our findings thus reveal a potential therapeutic approach for treating resistance to CSF-1R inhibitors. PMID- 27199443 TI - Simultaneous Analysis of Quercetin and Naringenin in Rat Plasma by Liquid Chromatography-Tandem Mass Spectrometry: Application to a Pharmacokinetic Study After Oral Administration. AB - A rapid and specific LC-MS-MS method has been developed for simultaneous analysis of quercetin and naringenin in rat plasma. The method was applied to the pharmacokinetics studies of quercetin and naringenin after oral administration of Pollen Typhae extract. The samples were prepared by the protein precipitation method. The analysis was carried out on an ACQUITY UPLCTM BEH C18 column with gradient elution using mobile phase, which included acetonitrile and water (containing 0.1% formic acid). The flow rate was 0.4 mL/min. All analytes including internal standard (IS) were monitored by selected reaction monitoring with an electrospray ionization source. Linear responses were obtained for quercetin ranging from 0.5 to 100 ng/mL and naringenin ranging from 5 to 1000 ng/mL. The intra- and interday precisions (RSD) were less than 10.78 and 11.20%. The extraction recovery of the analytes was acceptable. Stability studies showed that quercetin and naringenin were stable in the preparation and analytical process. The validated method was successfully used to determine the concentration-time profiles of quercetin and naringenin. PMID- 27199444 TI - A Rapid and Sensitive HPLC-DAD Assay to Quantify Lamotrigine, Phenytoin and Its Main Metabolite in Samples of Cultured HepaRG Cells. AB - A sensitive and fast high-performance liquid chromatography-diode-array detection assay was developed and validated for the simultaneous quantification of 5-(4 hydroxyphenyl)-5-phenylhydantoin (HPPH), phenytoin (PHT) and lamotrigine (LTG) in samples of cultured HepaRG cells. Chromatographic separation of analytes and internal standard (IS) was achieved in ~15 min on a C18-column, at 35 degrees C, using acetonitrile (6%), methanol (25%) and a mixture (69%) of water triethylamine (99.7:0.3, v/v; pH 6.0), pumped at 1 mL/min. The analytes and IS were detected at 215 or 235 nm. Calibration curves were linear with regression coefficients >0.994 over the concentration ranges of 0.1-15 ug/mL for HPPH; 0.15 30 ug/mL for PHT and 0.2-20 ug/mL for LTG. The method showed to be accurate (bias value of +/-10.5 or +/-17.6% in the lower limit of quantification, LLOQ) and precise (coefficient variation <=8.1 or <=15.4% in the LLOQ), and the absolute recovery of the analytes ranged from 62.5 to 96.9%. HepaRG cells have emerged as a very promising in vitro model to evaluate metabolic, drug interaction and/or pharmacokinetic studies, and this methodology will be suitable to support subsequent studies involving the antiepileptic drugs PHT and LTG. PMID- 27199445 TI - JMJD8 Regulates Angiogenic Sprouting and Cellular Metabolism by Interacting With Pyruvate Kinase M2 in Endothelial Cells. AB - OBJECTIVE: Jumonji C (JmjC) domain-containing proteins modify histone and nonhistone proteins thereby controlling cellular functions. However, the role of JmjC proteins in angiogenesis is largely unknown. Here, we characterize the expression of JmjC domain-containing proteins after inducing endothelial differentiation of murine embryonic stem cells and study the function of JmjC domain-only proteins in endothelial cell (EC) functions. APPROACH AND RESULTS: We identified a large number of JmjC domain-containing proteins regulated by endothelial differentiation of murine embryonic stem cells. Among the family of JmjC domain-only proteins, Jmjd8 was significantly upregulated on endothelial differentiation. Knockdown of Jmjd8 in ECs significantly decreased in vitro network formation and sprouting in the spheroid assay. JMJD8 is exclusively detectable in the cytoplasm, excluding a function as a histone-modifying enzyme. Mass spectrometry analysis revealed JMJD8-interacting proteins with known functions in cellular metabolism like pyruvate kinase M2. Accordingly, knockdown of pyruvate kinase M2 in human umbilical vein ECs decreased endothelial sprouting in the spheroid assay. Knockdown of JMJD8 caused a reduction of EC metabolism as measured by Seahorse Bioscience extracellular flux analysis. Conversely, overexpression of JMJD8 enhanced cellular oxygen consumption rate of ECs, reflecting an increased mitochondrial respiration. CONCLUSIONS: Jmjd8 is upregulated during endothelial differentiation and regulates endothelial sprouting and metabolism by interacting with pyruvate kinase M2. PMID- 27199447 TI - Wnt2 and WISP-1/CCN4 Induce Intimal Thickening via Promotion of Smooth Muscle Cell Migration. AB - OBJECTIVE: Increased vascular smooth muscle cell (VSMC) migration leads to intimal thickening which acts as a soil for atherosclersosis, as well as causing coronary artery restenosis after stenting and vein graft failure. Investigating factors involved in VSMC migration may enable us to reduce intimal thickening and improve patient outcomes. In this study, we determined whether Wnt proteins regulate VSMC migration and thereby intimal thickening. APPROACH AND RESULTS: Wnt2 mRNA and protein expression were specifically increased in migrating mouse aortic VSMCs. Moreover, VSMC migration was induced by recombinant Wnt2 in vitro. Addition of recombinant Wnt2 protein increased Wnt1-inducible signaling pathway protein-1 (WISP-1) mRNA by ~1.7-fold, via beta-catenin/T-cell factor signaling, whereas silencing RNA knockdown of Wnt-2 reduced WISP-1 mRNA by ~65%. Treatment with rWISP-1 significantly increased VSMC migration by ~1.5-fold, whereas WISP-1 silencing RNA knockdown reduced migration by ~40%. Wnt2 and WISP-1 effects were integrin-dependent and not additive, indicating that Wnt2 promoted VSMC migration via WISP-1. Additionally, Wnt2 and WISP-1 were significantly increased and colocated in human coronary arteries with intimal thickening. Reduced Wnt2 and WISP-1 levels in mouse carotid arteries from Wnt2(+/-) and WISP-1(-/-) mice, respectively, significantly suppressed intimal thickening in response to carotid artery ligation. In contrast, elevation of plasma WISP-1 via an adenovirus encoding WISP-1 significantly increased intimal thickening by ~1.5-fold compared with mice receiving control virus. CONCLUSIONS: Upregulation of Wnt2 expression enhanced WISP-1 and promoted VSMC migration and thereby intimal thickening. As novel regulators of VSMC migration and intimal thickening, Wnt2 or WISP-1 may provide a potential therapy for restenosis and vein graft failure. PMID- 27199446 TI - Molecular Characterization of the Lipid Genome-Wide Association Study Signal on Chromosome 18q11.2 Implicates HNF4A-Mediated Regulation of the TMEM241 Gene. AB - OBJECTIVE: We recently identified a locus on chromosome 18q11.2 for high serum triglycerides in Mexicans. We hypothesize that the lead genome-wide association study single-nucleotide polymorphism rs9949617, or its linkage disequilibrium proxies, regulates 1 of the 5 genes in the triglyceride-associated region. APPROACH AND RESULTS: We performed a linkage disequilibrium analysis and found 9 additional variants in linkage disequilibrium (r(2)>0.7) with the lead single nucleotide polymorphism. To select the variants for functional analyses, we annotated the 10 variants using DNase I hypersensitive sites, transcription factor and chromatin states and identified rs17259126 as the lead candidate variant for functional in vitro validation. Using luciferase transcriptional reporter assay in liver HepG2 cells, we found that the G allele exhibits a significantly lower effect on transcription (P<0.05). The electrophoretic mobility shift and ChIPqPCR (chromatin immunoprecipitation coupled with quantitative polymerase chain reaction) assays confirmed that the minor G allele of rs17259126 disrupts an hepatocyte nuclear factor 4 alpha-binding site. To find the regional candidate gene, we performed a local expression quantitative trait locus analysis and found that rs17259126 and its linkage disequilibrium proxies alter expression of the regional transmembrane protein 241 (TMEM241) gene in 795 adipose RNAs from the Metabolic Syndrome In Men (METSIM) cohort (P=6.11*10(-07) 5.80*10(-04)). These results were replicated in expression profiles of TMEM241 from the Multiple Tissue Human Expression Resource (MuTHER; n=856). CONCLUSIONS: The Mexican genome-wide association study signal for high serum triglycerides on chromosome 18q11.2 harbors a regulatory single-nucleotide polymorphism, rs17259126, which disrupts normal hepatocyte nuclear factor 4 alpha binding and decreases the expression of the regional TMEM241 gene. Our data suggest that decreased transcript levels of TMEM241 contribute to increased triglyceride levels in Mexicans. PMID- 27199448 TI - Calmodulin Mediates Ca2+-Dependent Inhibition of Tie2 Signaling and Acts as a Developmental Brake During Embryonic Angiogenesis. AB - OBJECTIVE: Angiogenesis, the process of building complex vascular structures, begins with sprout formation on preexisting blood vessels, followed by extension of the vessels through proliferation and migration of endothelial cells. Based on the potential therapeutic benefits of preventing angiogenesis in pathological conditions, many studies have focused on the mechanisms of its initiation as well as control. However, how the extension of vessels is terminated remains obscure. Thus, we investigated the negative regulation mechanism. APPROACH AND RESULTS: We report that increased intracellular calcium can induce dephosphorylation of the endothelial receptor tyrosine kinase Tie2. The calcium-mediated dephosphorylation was found to be dependent on Tie2-calmodulin interaction. The Tyr1113 residue in the C-terminal end loop of the Tie2 kinase domain was mapped and found to be required for this interaction. Moreover, mutation of this residue into Phe impaired both the Tie2-calmodulin interaction and calcium-mediated Tie2 dephosphorylation. Furthermore, expressing a mutant Tie2 incapable of binding to calmodulin or inhibiting calmodulin function in vivo causes unchecked growth of the vasculature in Xenopus. Specifically, knockdown of Tie2 in Xenopus embryo retarded the sprouting and extension of intersomitic veins. Although human Tie2 expression in the Tie2-deficient animals almost completely rescued the retardation, the Tie2(Y1113F) mutant caused overgrowth of intersomitic veins with strikingly complex and excessive branching patterns. CONCLUSIONS: We propose that the calcium/calmodulin-dependent negative regulation of Tie2 can be used as an inhibitory signal for vessel growth and branching to build proper vessel architecture during embryonic development. PMID- 27199449 TI - Bone Morphogenetic Protein Signaling Is Required for Aortic Valve Calcification. AB - OBJECTIVE: Calcific aortic valve disease (CAVD) is the most prevalent type of heart valve disease, affecting ~2% of the US population. CAVD is characterized by the presence of calcific nodules, resulting in aortic valve (AoV) stenosis; however, the underlying mechanisms driving disease remain unknown. Studies of human diseased AoV provide initial evidence that bone morphogenetic protein (BMP) signaling, essential for normal bone formation, is activated during CAVD. Mice deficient in Klotho, an FGF23 transmembrane coreceptor, exhibit premature aging and develop AoV calcific nodules as occurs in human CAVD. The role of BMP signaling in the development of CAVD was examined in porcine aortic valve interstitial cells (VICs) and Klotho(-/-) mice. APPROACH AND RESULTS: We show that activation of BMP signaling, as indicated by pSmad1/5/8 expression, precedes and later localizes with AoV calcification in Klotho(-/-) mice. In addition, cellular and extracellular matrix changes resembling features of normal bone formation are accompanied by increased osteochondrogenic gene induction in calcified Klotho(-/-) AoV. Likewise, osteogenic media treatment of porcine VICs results in BMP pathway activation, increased osteochondrogenic gene induction, and formation of calcific nodules in vitro. We demonstrate that genetic inactivation of the BMP type IA receptor in Klotho(-/-) aortic VICs, as well as BMP pathway inhibition of osteogenic media-treated aortic VICs in vitro, results in the inhibition of AoV calcification. CONCLUSIONS: BMP signaling and osteochondrogenic gene induction are active in calcified Klotho(-/-) AoV in vivo and calcified porcine aortic VICs in vitro. Importantly, BMP signaling is required for the development of AoV calcification in vitro and in vivo. PMID- 27199451 TI - Oncological miR-182-3p, a Novel Smooth Muscle Cell Phenotype Modulator, Evidences From Model Rats and Patients. AB - OBJECTIVE: Vascular smooth muscle cell (VSMC) phenotype change is a hallmark of vascular remodeling, which contributes to atherosclerotic diseases and can be regulated via microRNA-dependent mechanisms. We recently identified that asymmetrical dimethylarginine positively correlates to vascular remodeling-based diseases. We hypothesized that asymmetrical dimethylarginine induces smooth muscle cell (SMC) phenotypic change via a microRNA-dependent mechanism. APPROACH AND RESULTS: Microarray analysis enabled the identification of downregulation of miR-182-3p in asymmetrical dimethylarginine-treated human aortic artery SMCs. The myeloid-associated differentiation marker (MYADM) was identified as the downstream target of miR-182-3p and implicated to contribute to miR-182-3p knockdown-mediated SMC phenotype change, which was evidenced by the increased proliferation and migration and reduced expression levels of phenotype-related genes in human aortic artery SMCs through the ERK/MAP (extracellular signal regulated kinase/mitogen-activated protein) kinase-dependent mechanism. When inhibiting MYADM in the presence of miR-182-3p inhibitor or overexpressing MYADM in the presence of pre-miR-182-3p, human aortic artery SMCs were reversed to the differentiation phenotype. In vivo, adeno-miR-182-3p markedly suppressed carotid neointimal formation by using balloon-injured rat carotid artery model, specifically via decreased MYADM expression, whereas adeno-miR-182-3p inhibitor significantly promoted neointimal formation. Atherosclerotic lesions from patients with high asymmetrical dimethylarginine plasma levels exhibited decreased miR-182-3p expression levels and elevated MYADM expression levels. CONCLUSIONS: miR-182-3p is a novel SMC phenotypic modulator by targeting MYADM. PMID- 27199450 TI - Deficiency of ATP-Binding Cassette Transporters A1 and G1 in Endothelial Cells Accelerates Atherosclerosis in Mice. AB - OBJECTIVE: Plasma high-density lipoproteins have several putative antiatherogenic effects, including preservation of endothelial functions. This is thought to be mediated, in part, by the ability of high-density lipoproteins to promote cholesterol efflux from endothelial cells (ECs). The ATP-binding cassette transporters A1 and G1 (ABCA1 and ABCG1) interact with high-density lipoproteins to promote cholesterol efflux from ECs. To determine the impact of endothelial cholesterol efflux pathways on atherogenesis, we prepared mice with endothelium specific knockout of Abca1 and Abcg1. APPROACH AND RESULTS: Generation of mice with EC-ABCA1 and ABCG1 deficiency required crossbreeding Abca1(fl/fl)Abcg1(fl/fl)Ldlr(-/-) mice with the Tie2Cre strain, followed by irradiation and transplantation of Abca1(fl/fl)Abcg1(fl/fl) bone marrow to abrogate the effects of macrophage ABCA1 and ABCG1 deficiency induced by Tie2Cre. After 20 to 22 weeks of Western-type diet, both single EC-Abca1 and Abcg1 deficiency increased atherosclerosis in the aortic root and whole aorta. Combined EC-Abca1/g1 deficiency caused a significant further increase in lesion area at both sites. EC-Abca1/g1 deficiency dramatically enhanced macrophage lipid accumulation in the branches of the aorta that are exposed to disturbed blood flow, decreased aortic endothelial NO synthase activity, and increased monocyte infiltration into the atherosclerotic plaque. Abca1/g1 deficiency enhanced lipopolysaccharide-induced inflammatory gene expression in mouse aortic ECs, which was recapitulated by ABCG1 deficiency in human aortic ECs. CONCLUSIONS: These studies provide direct evidence that endothelial cholesterol efflux pathways mediated by ABCA1 and ABCG1 are nonredundant and atheroprotective, reflecting preservation of endothelial NO synthase activity and suppression of endothelial inflammation, especially in regions of disturbed arterial blood flow. PMID- 27199452 TI - High-throughput sequencing reveals differential expression of miRNAs in prehierarchal follicles of laying and brooding geese. AB - Broodiness is the primary factor influencing egg production in geese, in which several genes and miRNAs participate. Detailed spatiotemporal profiles of miRNAs encompassing follicle development levels, however, are lacking. In this study, we collected preovulatory follicles (classified as small white follicles, large white follicles, and small yellow follicles) from brooding and laying geese and aimed to analyze microRNA (miRNA or miR) during folliculogenesis. High-throughput sequencing and bioinformatics analysis were used to identify the miRNAs involved in follicle development. The let7 family, miR-10 family, and miR-143 family were abundant in these libraries, and they have been suggested to play a housekeeping role during folliculogenesis. Joint comparisons revealed 23 upregulated and 21 downregulated miRNAs (in at least two comparisons of follicles during brooding and laying, P < 0.1) in the laying stage. Unlike reproduction pathways reported for ovaries, GO and KEGG analysis suggested pathways for cell apoptosis and proliferation, such as the regulation of actin cytoskeleton, endocytosis, axon guidance, pathways in cancer, tight junctions, focal adhesion, the MAPK signaling pathway, cytokine-cytokine receptor interactions, and the Wnt signaling pathway in folliculogenesis. This study revealed the miRNAs that were directly involved in follicular atresia, and our results added to the understanding of the functional involvement of miRNAs during specific stages of follicle development. PMID- 27199454 TI - Comprehensive database of human E3 ubiquitin ligases: application to aquaporin-2 regulation. AB - Aquaporin-2 (AQP2) is regulated in part via vasopressin-mediated changes in protein half-life that are in turn dependent on AQP2 ubiquitination. Here we addressed the question, "What E3 ubiquitin ligase is most likely to be responsible for AQP2 ubiquitination?" using large-scale data integration based on Bayes' rule. The first step was to bioinformatically identify all E3 ligase genes coded by the human genome. The 377 E3 ubiquitin ligases identified in the human genome, consisting predominant of HECT, RING, and U-box proteins, have been used to create a publically accessible and downloadable online database (https://hpcwebapps.cit.nih.gov/ESBL/Database/E3-ligases/). We also curated a second database of E3 ligase accessory proteins that included BTB domain proteins, cullins, SOCS-box proteins, and F-box proteins. Using Bayes' theorem to integrate information from multiple large-scale proteomic and transcriptomic datasets, we ranked these 377 E3 ligases with respect to their probability of interaction with AQP2. Application of Bayes' rule identified the E3 ligases most likely to interact with AQP2 as (in order of probability): NEDD4 and NEDD4L (tied for first), AMFR, STUB1, ITCH, ZFPL1. Significantly, the two E3 ligases tied for top rank have also been studied extensively in the reductionist literature as regulatory proteins in renal tubule epithelia. The concordance of conclusions from reductionist and systems-level data provides strong motivation for further studies of the roles of NEDD4 and NEDD4L in the regulation of AQP2 protein turnover. PMID- 27199455 TI - Effect of selective expression of dominant-negative PPARgamma in pro opiomelanocortin neurons on the control of energy balance. AB - Peroxisome proliferator-activated receptor-gamma (PPARgamma), a master regulator of adipogenesis, was recently shown to affect energy homeostasis through its actions in the brain. Deletion of PPARgamma in mouse brain, and specifically in the pro-opiomelanocortin (POMC) neurons, results in resistance to diet-induced obesity. To study the mechanisms by which PPARgamma in POMC neurons controls energy balance, we constructed a Cre-recombinase-dependent conditionally activatable transgene expressing either wild-type (WT) or dominant-negative (P467L) PPARgamma and the tdTomato reporter. Inducible expression of both forms of PPARgamma was validated in cells in culture, in liver of mice infected with an adenovirus expressing Cre-recombinase (AdCre), and in the brain of mice expressing Cre-recombinase either in all neurons (NES(Cre)/PPARgamma-P467L) or selectively in POMC neurons (POMC(Cre)/PPARgamma-P467L). Whereas POMC(Cre)/PPARgamma-P467L mice exhibited a normal pattern of weight gain when fed 60% high-fat diet, they exhibited increased weight gain and fat mass accumulation in response to a 10% fat isocaloric-matched control diet. POMC(Cre)/PPARgamma P467L mice were leptin sensitive on control diet but became leptin resistant when fed 60% high-fat diet. There was no difference in body weight between POMC(Cre)/PPARgamma-WT mice and controls in response to 60% high-fat diet. However, POMC(Cre)/PPARgamma-WT, but not POMC(Cre)/PPARgamma-P467L, mice increased body weight in response to rosiglitazone, a PPARgamma agonist. These observations support the concept that alterations in PPARgamma-driven mechanisms in POMC neurons can play a role in the regulation of metabolic homeostasis under certain dietary conditions. PMID- 27199453 TI - Heterotrimeric G protein signaling in polycystic kidney disease. AB - Autosomal dominant polycystic kidney disease (ADPKD) is a signalopathy of renal tubular epithelial cells caused by naturally occurring mutations in two distinct genes, polycystic kidney disease 1 (PKD1) and 2 (PKD2). Genetic variants in PKD1, which encodes the polycystin-1 (PC-1) protein, remain the predominant factor associated with the pathogenesis of nearly two-thirds of all patients diagnosed with PKD. Although the relationship between defective PC-1 with renal cystic disease initiation and progression remains to be fully elucidated, there are numerous clinical studies that have focused upon the control of effector systems involving heterotrimeric G protein regulation. A major regulator in the activation state of heterotrimeric G proteins are G protein-coupled receptors (GPCRs), which are defined by their seven transmembrane-spanning regions. PC-1 has been considered to function as an unconventional GPCR, but the mechanisms by which PC-1 controls signal processing, magnitude, or trafficking through heterotrimeric G proteins remains to be fully known. The diversity of heterotrimeric G protein signaling in PKD is further complicated by the presence of non-GPCR proteins in the membrane or cytoplasm that also modulate the functional state of heterotrimeric G proteins within the cell. Moreover, PC-1 abnormalities promote changes in hormonal systems that ultimately interact with distinct GPCRs in the kidney to potentially amplify or antagonize signaling output from PC-1. This review will focus upon the canonical and noncanonical signaling pathways that have been described in PKD with specific emphasis on which heterotrimeric G proteins are involved in the pathological reorganization of the tubular epithelial cell architecture to exacerbate renal cystogenic pathways. PMID- 27199457 TI - Minireview: Role of genetic changes of faciogenital dysplasia protein 1 in human disease. AB - The FGD1 gene encodes for a guanine exchange factor (GEF) protein that specifically activates the Rho GTPase Cdc42. For cellular migration, Cdc42 is a key molecular switch that regulates cytoskeleton restructuring, gene transcription, cellular morphology, extension, and cell adhesion. In the past decade, germline mutations in the FGD1 gene have been associated with a rare X linked disorder known as faciogenital dysplasia (FGDY). Malformations are consistent with a loss of cellular migration during embryonic development. Insertion and deletion mutations in FGD1 result in a frameshift causing inactivation of fgd1 protein. Since Cdc42 is a key molecular switch in cytoskeletal restructuring and cell adhesion, the loss of fgd1 is postulated to attenuate Cdc42-mediated cellular migration in embryonic development. In metastatic tumors, Cdc42 modulates migration and invasiveness. Fgd1 overexpression has been found in infiltrating and poorly differentiated breast and invasive prostate tumors. Amplification at Xp11.21, the FGD1 gene locus, has been reported in several cancers. Sequencing analyses in numerous types of cancer have found missense mutations in the FGD1 gene in metastatic tumors. FGDY and cancer studies suggest that the germline and somatic changes downregulate or upregulate the FGD1 gene playing a key role in the development of diseases. PMID- 27199456 TI - Retinoic acid and sodium butyrate suppress the cardiac expression of hypertrophic markers and proinflammatory mediators in Npr1 gene-disrupted haplotype mice. AB - The objective of the present study was to examine the genetically determined differences in the natriuretic peptide receptor-A (NPRA) gene (Npr1) copies affecting the expression of cardiac hypertrophic markers, proinflammatory mediators, and matrix metalloproteinases (MMPs) in a gene-dose-dependent manner. We determined whether stimulation of Npr1 by all-trans retinoic acid (RA) and histone deacetylase (HDAC) inhibitor sodium butyric acid (SB) suppress the expression of cardiac disease markers. In the present study, we utilized Npr1 gene-disrupted heterozygous (Npr1(+/-), 1-copy), wild-type (Npr1(+/+), 2-copy), gene-duplicated (Npr1(++/+), 3-copy) mice, which were treated intraperitoneally with RA, SB, and a combination of RA/SB, a hybrid drug (HB) for 2 wk. Untreated 1 copy mice showed significantly increased heart weight-body weight (HW/BW) ratio, blood pressure, hypertrophic markers, including beta-myosin heavy chain (beta MHC) and proto-oncogenes (c-fos and c-jun), proinflammatory mediator nuclear factor kappa B (NF-kappaB), and MMPs (MMP-2, MMP-9) compared with 2-copy and 3 copy mice. The heterozygous (haplotype) 1-copy mice treated with RA, SB, or HB, exhibited significant reduction in the expression of beta-MHC, c-fos, c-jun, NF kappaB, MMP-2, and MMP-9. In drug-treated animals, the activity and expression levels of HDAC were significantly reduced and histone acetyltransferase activity and expression levels were increased. The drug treatments significantly increased the fractional shortening and reduced the systolic and diastolic parameters of the Npr1(+/-) mice hearts. Together, the present results demonstrate that a decreased Npr1 copy number enhanced the expression of hypertrophic markers, proinflammatory mediators, and MMPs, whereas an increased Npr1 repressed the cardiac disease markers in a gene-dose-dependent manner. PMID- 27199458 TI - Discovery and identification of candidate sex-related genes based on transcriptome sequencing of Russian sturgeon (Acipenser gueldenstaedtii) gonads. AB - As the Russian sturgeon (Acipenser gueldenstaedtii) is an important food and is the main source of caviar, it is necessary to discover the genes associated with its sex differentiation. However, the complicated life and maturity cycles of the Russian sturgeon restrict the accurate identification of sex in early development. To generate a first look at specific sex-related genes, we sequenced the transcriptome of gonads in different development stages (1, 2, and 5 yr old stages) with next-generation RNA sequencing. We generated >60 million raw reads, and the filtered reads were assembled into 263,341 contigs, which produced 38,505 unigenes. Genes involved in signal transduction mechanisms were the most abundant, suggesting that development of sturgeon gonads is under control of signal transduction mechanisms. Differentially expressed gene analysis suggests that more genes for protein synthesis, cytochrome c oxidase subunits, and ribosomal proteins were expressed in female gonads than in male. Meanwhile, male gonads expressed more transposable element transposase, reverse transcriptase, and transposase-related genes than female. In total, 342, 782, and 7,845 genes were detected in intersex, male, and female transcriptomes, respectively. The female gonad expressed more genes than the male gonad, and more genes were involved in female gonadal development. Genes (sox9, foxl2) are differentially expressed in different sexes and may be important sex-related genes in Russian sturgeon. Sox9 genes are responsible for the development of male gonads and foxl2 for female gonads. PMID- 27199459 TI - Tumor purity and differential methylation in cancer epigenomics. AB - DNA methylation is an epigenetic modification of DNA molecule that plays a vital role in gene expression regulation. It is not only involved in many basic biological processes, but also considered an important factor for tumorigenesis and other human diseases. Study of DNA methylation has been an active field in cancer epigenomics research. With the advances of high-throughput technologies and the accumulation of enormous amount of data, method development for analyzing these data has gained tremendous interests in the fields of computational biology and bioinformatics. In this review, we systematically summarize the recent developments of computational methods and software tools in high-throughput methylation data analysis with focus on two aspects: differential methylation analysis and tumor purity estimation in cancer studies. PMID- 27199460 TI - Implementation of Molecular Surveillance After a Cluster of Fatal Toxoplasmosis at 2 Neighboring Transplant Centers. AB - After a cluster of fatal toxoplasmosis among stem cell transplant recipients at 2 hospitals, surveillance with polymerase chain reaction (PCR) (blood) was instituted. Rate of reactivation among seropositive recipients was 2.2 and 16%. Parasitemia was successfully managed with preemptive treatment. For seropositive recipients unable to take prophylaxis, toxoplasma PCR surveillance should be routinely performed. PMID- 27199462 TI - Antibiotic Stewardship Programs in U.S. Acute Care Hospitals: Findings From the 2014 National Healthcare Safety Network Annual Hospital Survey. AB - BACKGROUND: The National Action Plan to Combat Antibiotic Resistant Bacteria calls for all US hospitals to improve antibiotic prescribing as a key prevention strategy for resistance and Clostridium difficile Antibiotic stewardship programs (ASPs) will be important in this effort but implementation is not well understood. METHODS: We analyzed the 2014 National Healthcare Safety Network Annual Hospital Survey to describe ASPs in US acute care hospitals as defined by the Center for Disease Control and Prevention's (CDC) Core Elements for Hospital ASPs. Univariate analyses were used to assess stewardship infrastructure and practices by facility characteristics and a multivariate model determined factors associated with meeting all ASP core elements. RESULTS: Among 4184 US hospitals, 39% reported having an ASP that met all 7 core elements. Although hospitals with greater than 200 beds (59%) were more likely to have ASPs, 1 in 4 (25%) of hospitals with less than 50 beds reported achieving all 7 CDC-defined core elements of a comprehensive ASP. The percent of hospitals in each state that reported all seven elements ranged from 7% to 58%. In the multivariate model, written support (adjusted relative risk [RR] 7.2 [95% confidence interval [CI], 6.2-8.4]; P < .0001) or salary support (adjusted RR 1.5 [95% CI, 1.4-1.6]; P < .0001) were significantly associated with having a comprehensive ASP. CONCLUSIONS: Our findings show that ASP implementation varies across the United States and provide a baseline to monitor progress toward national goals. Comprehensive ASPs can be established in facilities of any size and hospital leadership support for antibiotic stewardship appears to drive the establishment of ASPs. PMID- 27199463 TI - Editorial Commentary: Antimicrobial Stewardship in US Hospitals: Is the Cup Half full Yet? PMID- 27199461 TI - The Veterans Aging Cohort Study (VACS) Index and Neurocognitive Change: A Longitudinal Study. AB - BACKGROUND: The Veterans Aging Cohort Study (VACS) Index, a composite marker of disease severity among human immunodeficiency virus (HIV)-infected persons, has been associated with concurrent risk for neurocognitive impairment (NCI). The present study examined whether the VACS Index predicts longitudinal neurocognitive change. METHODS: Participants included 655 HIV-infected persons followed for up to 6 years in cohort studies at the University of California, San Diego, HIV Neurobehavioral Research Program (mean age at baseline, 42.5 years; 83% male; 60% white; AIDS in 67%; median current CD4(+) T-cell count, 346/MUL; 61% receiving antiretroviral therapy). The VACS Index was calculated through standard methods. Participants completed a comprehensive neurocognitive battery. Neurocognitive status was plotted over time using demographically and practice adjusted global and domain T scores. NCI was defined by global deficit scores derived from T scores. RESULTS: Baseline VACS Index scores were not predictive of changes in global T scores during the follow-up period (P = .14). However, in time-dependent analyses adjusting for covariates, higher VACS Index scores were significantly associated with worse global and domain neurocognitive performance (Ps < .01), as well as increased risk for developing NCI in a subgroup of persons who were neurocognitively normal at baseline (hazard ratio [HR], 1.17; P < .001). We categorized VACS Index scores by quartiles and found that the upper-quartile group was significantly more likely to develop NCI than the lower quartile (HR, 2.16; P < .01) and middle groups (HR, 1.76; P < .01). CONCLUSIONS: Changes in VACS Index scores correspond to changes in neurocognitive function. HIV-infected persons with high VACS Index scores are at increased risk for decline and incident NCI. The VACS Index shows promise as a tool for identifying HIV-infected persons at risk for NCI. PMID- 27199464 TI - ADAR1-Mediated RNA Editing, A Novel Mechanism Controlling Phenotypic Modulation of Vascular Smooth Muscle Cells. AB - RATIONALE: Vascular smooth muscle cell (SMC) phenotypic modulation is characterized by the downregulation of SMC contractile genes. Platelet-derived growth factor-BB, a well-known stimulator of SMC phenotypic modulation, downregulates SMC genes via posttranscriptional regulation. The underlying mechanisms, however, remain largely unknown. OBJECTIVE: To establish RNA editing as a novel mechanism controlling SMC phenotypic modulation. METHODS AND RESULTS: Precursor mRNAs (pre-mRNA) of SMC myosin heavy chain and smooth muscle alpha actin were accumulated while their mature mRNAs were downregulated during SMC phenotypic modulation, suggesting an abnormal splicing of the pre-mRNAs. The abnormal splicing resulted from SMC marker pre-mRNA editing that was facilitated by adenosine deaminase acting on RNA 1 (ADAR1), an enzyme converting adenosines to inosines (A->I editing) in RNA sequences. ADAR1 expression inversely correlated with SMC myosin heavy chain and smooth muscle alpha-actin levels; knockdown of ADAR1 restored SMC myosin heavy chain and smooth muscle alpha-actin expression in phenotypically modulated SMC, and editase domain mutation diminished the ADAR1-mediated abnormal splicing of SMC marker pre-mRNAs. Moreover, the abnormal splicing/editing of SMC myosin heavy chain and smooth muscle alpha-actin pre-mRNAs occurred during injury-induced vascular remodeling. Importantly, heterozygous knockout of ADAR1 dramatically inhibited injury-induced neointima formation and restored SMC marker expression, demonstrating a critical role of ADAR1 in SMC phenotypic modulation and vascular remodeling in vivo. CONCLUSIONS: Our results unraveled a novel molecular mechanism, that is, pre-mRNA editing, governing SMC phenotypic modulation. PMID- 27199466 TI - Survival Analysis After Extracorporeal Membrane Oxygenation in Critically Ill Adults: A Nationwide Cohort Study. AB - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) provides circulatory and respiratory support for patients with severe acute cardiopulmonary failure. The objective of this study was to examine the survival outcomes for patients who received ECMO. METHODS AND RESULTS: Adult patients who received ECMO from September 1, 2002, to December 31, 2012, were identified from the Taiwan National Health Insurance Database associated with coronary artery bypass graft surgery, myocardial infarction/cardiogenic shock, injury, and infection/septic shock. A Cox regression model was used to determine hazard ratios and to compare 30-day and 1-year survival rates with the myocardial infarction/cardiogenic shock group used as the reference. The mean+/-SD age of the 4227-patient cohort was 57+/-17 years, and 72% were male. The overall mortalities were 59.8% and 76.5% at 1 month and 1 year. Survival statistics deteriorated sharply when ECMO was required for >3 days. Acute (30-day) survival was more favorable in the infection/septic shock (n=1076; hazard ratio, 0.61; 95% confidence interval, 0.55-0.67), coronary artery bypass graft surgery (n=1077; hazard ratio, 0.68; 95% confidence interval, 0.61 0.75), and injury (n=369, hazard ratio, 0.82; 95% confidence interval, 0.70-0.95) groups. The extended survival rapidly approached an asymptote near 20% for the infection/septic shock, myocardial infarction/cardiogenic shock (n=1705), and coronary artery bypass graft surgery groups. The pattern of survival for the injury group was somewhat better, exceeding 30% at year-end. CONCLUSIONS: Regardless of initial pathology, patients requiring ECMO were critically ill with similar guarded prognoses. Those in the trauma group had somewhat better outcomes. Determining the efficacy and cost-effectiveness of ECMO should be a critical future goal. PMID- 27199465 TI - CD74-Downregulation of Placental Macrophage-Trophoblastic Interactions in Preeclampsia. AB - RATIONALE: We hypothesized that cluster of differentiation 74 (CD74) downregulation on placental macrophages, leading to altered macrophage trophoblast interaction, is involved in preeclampsia. OBJECTIVE: Preeclamptic pregnancies feature hypertension, proteinuria, and placental anomalies. Feto placental macrophages regulate villous trophoblast differentiation during placental development. Disturbance of this well-balanced regulation can lead to pathological pregnancies. METHODS AND RESULTS: We performed whole-genome expression analysis of placental tissue. CD74 was one of the most downregulated genes in placentas from preeclamptic women. By reverse transcriptase-polymerase chain reaction, we confirmed this finding in early-onset (<34 gestational week, n=26) and late-onset (>=34 gestational week, n=24) samples from preeclamptic women, compared with healthy pregnant controls (n=28). CD74 protein levels were analyzed by Western blot and flow cytometry. We identified placental macrophages to express CD74 by immunofluorescence, flow cytometry, and RT-PCR. CD74-positive macrophages were significantly reduced in preeclamptic placentas compared with controls. CD74-silenced macrophages showed that the adhesion molecules ALCAM, ICAM4, and Syndecan-2, as well as macrophage adhesion to trophoblasts were diminished. Naive and activated macrophages lacking CD74 showed a shift toward a proinflammatory signature with an increased secretion of tumor necrosis factor alpha, chemokine (C-C motif) ligand 5, and monocyte chemotactic protein-1, when cocultured with trophoblasts compared with control macrophages. Trophoblasts stimulated by these factors express more CYP2J2, sFlt1, TNFalpha, and IL-8. CD74 knockout mice showed disturbed placental morphology, reduced junctional zone, smaller placentas, and impaired spiral artery remodeling with fetal growth restriction. CONCLUSIONS: CD74 downregulation in placental macrophages is present in preeclampsia. CD74 downregulation leads to altered macrophage activation toward a proinflammatory signature and a disturbed crosstalk with trophoblasts. PMID- 27199467 TI - Longitudinal Assessment of Colonization With Staphylococcus aureus in Healthy Collegiate Athletes. AB - BACKGROUND: Staphylococcus aureus is the leading cause of skin and soft tissue infections in the United States, and S. aureus colonization increases the risk of infection. Although athletes have a higher risk of infection with S. aureus than the general population, most studies in athletes have not assessed colonization. METHODS: We conducted a prospective cohort study of Vanderbilt University varsity athletes from August 2008 to April 2010. We assessed nasal and oropharyngeal colonization with methicillin-susceptible S. aureus (MSSA) and methicillin resistant S. aureus (MRSA) strains by obtaining swabs at enrollment and monthly thereafter until the end of the study. The athletes were also monitored for skin and soft tissue infections. RESULTS: We enrolled 377 athletes and trainers (224 in contact sports and 153 in noncontact sports). The total S. aureus colonization prevalence ranged from 34% to 62%, and for MRSA it ranged from 8% to 29%. The colonization rate in the summer was significantly higher than that in the winter (odds ratio for MRSA [ORMRSA], 1.70 [95% confidence interval (CI), 1.23-2.35]; ORMSSA, 1.38 [95% CI, 1.05-1.82]). Of 603 MRSA isolates, 75% carried the staphylococcal cassette chromosome mec (SCCmec) type IV, and 5% carried the genes encoding Panton-Valentine leukocidin. Nine symptomatic S. aureus infections occurred, 7 of which were between July and September. CONCLUSIONS: The S. aureus colonization rate is higher than previously reported and fluctuated over time in this prospective cohort of athletes. The higher colonization prevalence during summer might explain the infectious outbreak during the summer months and may represent a key intervention time for preventing S. aureus disease in athletes. PMID- 27199468 TI - Interferon-Gamma Release Assays and Pediatric Public Health Tuberculosis Screening: The San Francisco Program Experience 2005 to 2008. AB - BACKGROUND: Interferon-gamma release assay utilization in pediatric tuberculosis (TB) screening is limited by a paucity of longitudinal experience, particularly in low-TB burden populations. METHODS: We conducted a retrospective review of QuantiFERON (QFT)-TB Gold results in San Francisco children from 2005 to 2008. Concordance with the tuberculin skin test (TST) was analyzed for a subset of children. Progression to active disease was determined through San Francisco and California TB registry matches. RESULTS: Of 1092 children <15 years of age, 853 (78%) were foreign-born, and 136 (12%) were exposed to active TB cases (contacts). QuantiFERON tests were positive in 72 of 1092 (7%) children; 15 of 136 (11%) recent contacts; 53 of 807 (7%) foreign-born noncontacts; and 4 of 149 (3%) US-born noncontacts. QuantiFERON-negative/TST-positive discordance was seen more often in foreign-born/bacille Calmette-Guerin (BCG)-vaccinated children <5 years of age (52 of 56, 93%) compared to those >= 5 years of age (90 of 123, 73%; P = .003). Foreign-born, BCG-vaccinated children were more than twice as likely to have a discordant (79%) result as US-born, non-BCG-vaccinated children (37%; P < .0001). During 5587 person-years of follow-up of untreated children, including 146 TST-positive/QFT-negative children, no cases of active TB were identified, consistent with a negative predictive value of 100%. CONCLUSIONS: Our experience supports the use of QFT to evaluate latent TB infection in children, particularly young BCG-vaccinated children. The proportion of QFT-positive results correlated with risk of exposure, and none of the untreated QFT-negative children developed TB. The low QFT-positive rate highlights the need for more selective testing based on current epidemiology and TB exposure risk. PMID- 27199469 TI - Pharmacokinetics of Once-Daily Darunavir/Ritonavir With and Without Etravirine in Human Immunodeficiency Virus-Infected Children, Adolescents, and Young Adults. AB - BACKGROUND: Limited data are available for once-daily (QD) darunavir (DRV)/ritonavir (r) in the pediatric population. Coadministration of etravirine (ETR) may alter the pharmacokinetics (PK) of DRV. We evaluated the PK interactions between DRV/r (QD) and ETR QD or twice-daily (BID) in children, adolescents, and young adults. METHODS: Human immunodeficiency virus-infected subjects 9 to < 24 years old on optimized background therapy including DRV/r 800/100 mg QD alone or combined with ETR 200 mg BID or ETR 400 mg QD were enrolled. Protocol-defined target drug exposure ranges based on adult data were used to assess the adequacy of each regimen. Intensive 24-hour blood sampling was performed, and PK parameters were determined using noncompartmental analysis. RESULTS: Thirty-one subjects (14 males) completed the study; 16 received DRV/r QD alone (group 1), 6 received DRV/r plus ETR BID (group 2A), and 9 received DRV/r plus ETR QD (group 2B). The geometric mean (90% confidence interval [CI] geometric mean) for DRV area under the curve at 24 hours (AUC24) was 57.9 (49.6 67.6), 74.9 (44.4-126.5), and 66.4 (50.8-86.9) mg * h/L for patients in groups 1, 2A, and 2B, respectively. The increased DRV exposure when coadministered with ETR was not statistically significant. The geometric mean (90% CI geometric mean) of ETR AUC24 was 8.6 (4.4-16.8) and 11.9 (7.5-18.9) mg * h/L for groups 2A and 2B, respectively, with comparable C24. CONCLUSIONS: The results suggest that DRV/r QD with ETR 400 mg QD or 200 mg BID is appropriate and support further evaluation of the safety and efficacy of the once-daily regimen in older children, adolescents, and young adults. PMID- 27199470 TI - Shiga Toxin-Producing Escherichia coli in Diarrheal Stool of Swedish Children: Evaluation of Polymerase Chain Reaction Screening and Duration of Shiga Toxin Shedding. AB - BACKGROUND: Shiga toxin (Stx)-producing Escherichia coli (STECs) are the most common cause of acute renal failure in children. The present study evaluated a 10 year STEC polymerase chain reaction screening regimen in children. METHODS: All routine stool culture specimens from patients below 10 years of age (n = 10 342) from May 2003 through April 2013 in the County of Jonkoping, Sweden, were included. Patients were divided in 1 group where analyses of STEC were requested by the clinician (n = 2366) and 1 screening group (n = 7976). Patients who were positive for STEC were tested weekly until they were negative. Clinical data were collected through a questionnaire and by reviewing medical records. RESULTS: In specimens from 191 patients, stx was found (162 index cases). The prevalence was 1.8% in the requested group and 1.5% in the screening group (P = .5). Diarrhea was the most frequent symptom reported in 156 cases and of these 29 (19%) had hemorrhagic colitis (HC) and 7 children developed hemolytic uremic syndrome (HUS). No difference regarding severity of symptoms between the groups was found. Stx2 predominated in cases with HC (P < .0001) and HUS (P = .04). Median stx shedding duration was 20 days (1-256 days), and no difference in duration was seen between stx types (P = .106-1.00) and presence of eaeA (P = .72). CONCLUSIONS: Most STEC cases were found in the screening group with comparable prevalence and disease severity as in patients where analysis was requested. Furthermore, non-O157 serotypes caused severe disease when carrying stx2, and prolonged shedding of STEC may be a risk for transmission. PMID- 27199471 TI - Febrile Seizures in the Era of Rotavirus Vaccine. AB - A protective association between rotavirus vaccination and childhood seizures in the year after vaccination was recently reported from the United States. In the state of Queensland, Australia, the authors found that rotavirus vaccine was 35.8% and 38.0% effective at preventing emergency department presentation and subsequent hospitalization, respectively, for febrile seizures among children up to two years following vaccination. PMID- 27199472 TI - Fecal Polyomavirus Excretion in Infancy. AB - Qualitative polymerase chain reaction (PCR) was used to determine the prevalence of fecal excretion of BK virus, JC virus, and simian virus 40 in 1-year-old infants. Overall, 17.8% of 321 specimens from 64.1% of 39 infants were polyomavirus positive. These data suggest that the gastrointestinal tract may be a site of polyomavirus persistence in humans. PMID- 27199473 TI - Pertussis Seasonality Evident in Polymerase Chain Reaction and Serological Testing Data, Queensland, Australia. AB - We investigated the seasonality of pertussis in Queensland, Australia, between 2008 and 2011 using notification and laboratory data. Polymerase chain reaction and serology testing data demonstrate that in the vaccine era, pertussis remains a seasonal illness, with annual peaks in summer months, and that the seasonality of notification data is masked by testing trends. PMID- 27199474 TI - Blood Cultures for Persistent Fever in Neutropenic Pediatric Patients Are of Low Diagnostic Yield. AB - The incidence of bacteremia at the onset of pediatric febrile neutropenia (FN) at 2 academically linked institutions was 9.84%, and subsequent blood cultures performed for children with persistent FN yielded an incidence of 4.21%. Until the risk factors for new-onset bacteremia in patients being treated for FN can be identified and diagnostic methods can be improved, compliance with national guidelines is recommended. PMID- 27199475 TI - Nasopharyngeal Pneumococcal Serotypes Before and After Mass Azithromycin Distributions for Trachoma. AB - Twenty-four Ethiopian communities were randomized to receive either (1) quarterly mass azithromycin distributions for trachoma for 1 year or (2) delayed treatment. Nasopharyngeal swabs collected from separate cross-sectional population-based samples of children were processed for Streptococcus pneumoniae Mass azithromycin did not significantly alter the pneumococcal serotype distribution, and hence it would not be expected to alter vaccine coverage. PMID- 27199480 TI - Bacterial beta-Kdo glycosyltransferases represent a new glycosyltransferase family (GT99). AB - Kdo (3-deoxy-d-manno-oct-2-ulosonic acid) is an eight-carbon sugar mostly confined to Gram-negative bacteria. It is often involved in attaching surface polysaccharides to their lipid anchors. alpha-Kdo provides a bridge between lipid A and the core oligosaccharide in all bacterial LPSs, whereas an oligosaccharide of beta-Kdo residues links "group 2" capsular polysaccharides to (lyso)phosphatidylglycerol. beta-Kdo is also found in a small number of other bacterial polysaccharides. The structure and function of the prototypical cytidine monophosphate-Kdo-dependent alpha-Kdo glycosyltransferase from LPS assembly is well characterized. In contrast, the beta-Kdo counterparts were not identified as glycosyltransferase enzymes by bioinformatics tools and were not represented among the 98 currently recognized glycosyltransferase families in the Carbohydrate-Active Enzymes database. We report the crystallographic structure and function of a prototype beta-Kdo GT from WbbB, a modular protein participating in LPS O-antigen synthesis in Raoultella terrigena The beta-Kdo GT has dual Rossmann-fold motifs typical of GT-B enzymes, but extensive deletions, insertions, and rearrangements result in a unique architecture that makes it a prototype for a new GT family (GT99). The cytidine monophosphate-binding site in the C-terminal alpha/beta domain closely resembles the corresponding site in bacterial sialyltransferases, suggesting an evolutionary connection that is not immediately evident from the overall fold or sequence similarities. PMID- 27199482 TI - Atomic-scale control of magnetic anisotropy via novel spin-orbit coupling effect in La2/3Sr1/3MnO3/SrIrO3 superlattices. AB - Magnetic anisotropy (MA) is one of the most important material properties for modern spintronic devices. Conventional manipulation of the intrinsic MA, i.e., magnetocrystalline anisotropy (MCA), typically depends upon crystal symmetry. Extrinsic control over the MA is usually achieved by introducing shape anisotropy or exchange bias from another magnetically ordered material. Here we demonstrate a pathway to manipulate MA of 3d transition-metal oxides (TMOs) by digitally inserting nonmagnetic 5d TMOs with pronounced spin-orbit coupling (SOC). High quality superlattices comprising ferromagnetic La2/3Sr1/3MnO3 (LSMO) and paramagnetic SrIrO3 (SIO) are synthesized with the precise control of thickness at the atomic scale. Magnetic easy-axis reorientation is observed by controlling the dimensionality of SIO, mediated through the emergence of a novel spin-orbit state within the nominally paramagnetic SIO. PMID- 27199483 TI - When a local Hamiltonian must be frustration-free. AB - A broad range of quantum optimization problems can be phrased as the question of whether a specific system has a ground state at zero energy, i.e., whether its Hamiltonian is frustration-free. Frustration-free Hamiltonians, in turn, play a central role for constructing and understanding new phases of matter in quantum many-body physics. Unfortunately, determining whether this is the case is known to be a complexity-theoretically intractable problem. This makes it highly desirable to search for efficient heuristics and algorithms to, at least, partially answer this question. Here we prove a general criterion-a sufficient condition-under which a local Hamiltonian is guaranteed to be frustration-free by lifting Shearer's theorem from classical probability theory to the quantum world. Remarkably, evaluating this condition proceeds via a fully classical analysis of a hardcore lattice gas at negative fugacity on the Hamiltonian's interaction graph, which, as a statistical mechanics problem, is of interest in its own right. We concretely apply this criterion to local Hamiltonians on various regular lattices, while bringing to bear the tools of spin glass physics that permit us to obtain new bounds on the satisfiable to unsatisfiable transition in random quantum satisfiability. We are then led to natural conjectures for when such bounds will be tight, as well as to a novel notion of universality for these computer science problems. Besides providing concrete algorithms leading to detailed and quantitative insights, this work underscores the power of marrying classical statistical mechanics with quantum computation and complexity theory. PMID- 27199484 TI - eHIV-STI: 5 years on.... PMID- 27199481 TI - MerTK cleavage limits proresolving mediator biosynthesis and exacerbates tissue inflammation. AB - The acute inflammatory response requires a coordinated resolution program to prevent excessive inflammation, repair collateral damage, and restore tissue homeostasis, and failure of this response contributes to the pathology of numerous chronic inflammatory diseases. Resolution is mediated in part by long chain fatty acid-derived lipid mediators called specialized proresolving mediators (SPMs). However, how SPMs are regulated during the inflammatory response, and how this process goes awry in inflammatory diseases, are poorly understood. We now show that signaling through the Mer proto-oncogene tyrosine kinase (MerTK) receptor in cultured macrophages and in sterile inflammation in vivo promotes SPM biosynthesis by a mechanism involving an increase in the cytoplasmic:nuclear ratio of a key SPM biosynthetic enzyme, 5-lipoxygenase. This action of MerTK is linked to the resolution of sterile peritonitis and, after ischemia-reperfusion (I/R) injury, to increased circulating SPMs and decreased remote organ inflammation. MerTK is susceptible to ADAM metallopeptidase domain 17 (ADAM17)-mediated cell-surface cleavage under inflammatory conditions, but the functional significance is not known. We show here that SPM biosynthesis is increased and inflammation resolution is improved in a new mouse model in which endogenous MerTK was replaced with a genetically engineered variant that is cleavage-resistant (Mertk(CR)). Mertk(CR) mice also have increased circulating levels of SPMs and less lung injury after I/R. Thus, MerTK cleavage during inflammation limits SPM biosynthesis and the resolution response. These findings contribute to our understanding of how SPM synthesis is regulated during the inflammatory response and suggest new therapeutic avenues to boost resolution in settings where defective resolution promotes disease progression. PMID- 27199485 TI - Assessing risk among MSM: service evaluation demonstrates feasibility of a single question approach. PMID- 27199486 TI - How easy is it to discuss party drug use with MSM? A Brighton clinic survey. PMID- 27199487 TI - Does the new 'jungle' migrant camp in Calais meet the intra-agency working group (IAWG) minimum standards for sexual and reproductive health (MISP) in an emergency situation? PMID- 27199488 TI - How are self-taken samples for chlamydia and gonorrhoea in HIV clinics perceived by patients? PMID- 27199489 TI - Long-term serial kinetics of N-terminal pro B-type natriuretic peptide and carbohydrate antigen 125 for mortality risk prediction following acute heart failure. AB - AIM: Baseline values of N-terminal pro B-type natriuretic peptide (NT-proBNP) and carbohydrate antigen 125 (CA125) predict all-cause mortality in acute heart failure (AHF). However, there is limited information about the added prognostic benefit of using longitudinal values, and how this predictive ability is modified when modelling together. The aim of this study was to determine the mutually adjusted association between the longitudinal trajectories of NT-proBNP and CA125 with all-cause mortality after an episode of AHF. METHODS AND RESULTS: We included 946 consecutive patients discharged for AHF. NT-proBNP and CA125 were measured at each physician-patient encounter (median (interquartile range (IQR)):3 (2-4)). The effect on mortality (time-dependent modelling) was assessed using joint modelling (JM) and multi-state Markov. The mean age was 71+/-11 years and 51% exhibited left ventricular systolic dysfunction. At a median follow-up of 2.64 years (IQR=1.20-5.36), 498 patients died (52.6%). The observed trajectories of both biomarkers markedly differed over survival status, with sustained higher values in patients who died. After being adjusted by established risk factors and by each other, the baseline absolute change in CA125 and NT-proBNP were significantly associated to mortality (hazard ratio (HR)=1.05 (1.01-1.09); p=0.011 (area under the curve (AUC)=0.76) and HR=1.04 (1.02-1.06); p<0.001 (AUC=0.75), respectively). After merging the binary version of NT-proBNP (?1000 pg/ml) and CA125 (>35 U/ml) into a four-level variable, we found the highest risk when both were elevated, intermediate risk when either one was low, and lowest risk when both were low. CONCLUSION: The combination of long-term longitudinal trajectories of CA125 and NT-proBNP improves risk stratification for all-cause mortality after a hospitalization for AHF. PMID- 27199491 TI - Age Bias in the Workplace: Cultural Stereotypes and In-Group Favoritism. AB - Two key theoretical frameworks that explain why people might hold biases for or against a specific age group-cultural stereotypes and in-group favoritism-yield distinct and sometimes contradictory predictions. This study proposes a combined framework drawing on these two theories and then tests hypotheses based on this framework in the workplace context. Using survey data from U.S. employees of two pharmaceutical companies, we evaluated the extent to which respondents attributed characteristics related to innovation or change and reliable performance to other workers based on perceived relative age (the age of the target relative to the age of the respondent). The hypotheses that our combined framework generated were supported, but the results varied by type of characteristic as well as by age of the respondent. We conclude that the combined framework is more predictive of age bias in the workplace than either individual framework alone. PMID- 27199492 TI - The Obama Administration's Cancer Moonshot: A Call for Proteomics. AB - The Cancer Moonshot Program has been launched and represents a potentially paradigm-shifting initiative with the goal to implement a focused national effort to double the rate of progress against cancer. The placement of precision medicine, immunotherapy, genomics, and combination therapies was placed at the central nexus of this initiative. Although we are extremely enthusiastic about the goals of the program, it is time we meet this revolutionary project with equally bold and cutting-edge ideas: it is time we move firmly into the postgenome era and provide the necessary resources to propel and seize on innovative recent gains in the field of proteomics required for it to stand on equal footing in this narrative as a combined, synergistic engine for molecular profiling. After all, although the genome is the information archive, it is the proteins that actually do the work of the cell and represent the structural cellular machinery. It is the proteins that comprise most of the biomarkers that are measured to detect cancers, constitute the antigens that drive immune response and inter- and intracellular communications, and it is the proteins that are the drug targets for nearly every targeted therapy that is being evaluated in cancer trials today. We believe that a combined systems biology view of the tumor microenvironment that orients cancer studies back to the functional proteome, phosphoproteome, and biochemistry of the cell will be essential to deliver on the promise of the Cancer Moonshot Program. Clin Cancer Res; 22(18); 4556-8. (c)2016 AACR. PMID- 27199490 TI - Emotional Intelligence Mediates the Relationship between Age and Subjective Well Being. AB - Individuals' Subjective Well-being (SWB) increases as they grow older. Past literature suggests that emotional intelligence may increase with age and lead to higher levels of SWB in older adults. The primary purpose of the present study was to test whether emotional intelligence would mediate the relationship between age and SWB. A total of 360 Chinese adults (age range: 20 to 79 years old) participated in this study. They filled out questionnaires that assessed their age, life satisfaction (The Satisfaction with Life Scale), affective well-being (The Positive and Negative Affect Schedule), and emotional intelligence (The Wong and Law Emotional Intelligence Scale). Using Structural Equation Modeling, the mediation model was supported, chi(2) (75) = 194.21, p < .01; RMSEA = .07; CFI = .91. Emotional intelligence partially mediated the relationship between age and life satisfaction, and fully mediated the relationship between age and affective well-being. The findings suggest that older adults may use their increased emotional intelligence to enhance their SWB. PMID- 27199493 TI - Ultrastructural Insights into the Biological Significance of Persisting DNA Damage Foci after Low Doses of Ionizing Radiation. AB - PURPOSE: Intensity-modulated radiotherapy (IMRT) enables the delivery of high doses to target volume while sparing surrounding nontargeted tissues. IMRT treatment, however, substantially increases the normal tissue volume receiving low-dose irradiation, but the biologic consequences are unclear. EXPERIMENTAL DESIGN: Using mouse strains that varied in genetic DNA repair capacity, we investigated the DNA damage response of cortical neurons during daily low-dose irradiation (0.1 Gy). Using light and electron microscopic approaches, we enumerated and characterized DNA damage foci as marker for double-strand breaks (DSBs). RESULTS: During repeated low-dose irradiation, cortical neurons in brain tissues of all mouse strains had a significant increase of persisting foci with cumulative doses, with the most pronounced accumulation of large-sized foci in repair-deficient mice. Electron microscopic analysis revealed that persisting foci in repair-proficient neurons reflect chromatin alterations in heterochromatin, but not persistently unrepaired DSBs. Repair-deficient SCID neurons, by contrast, showed high numbers of unrepaired DSBs in eu- and heterochromatin, emphasizing the fundamental role of DNA-PKcs in DSB rejoining, independent of chromatin status. In repair-deficient ATM-/- neurons, large persisting damage foci reflect multiple unrepaired DSBs concentrated at the boundary of heterochromatin due to disturbed KAP1 phosphorylation. CONCLUSION: Repeated low-dose irradiation leads to the accumulation of persisting DNA damage foci in cortical neurons and thus may adversely affect brain tissue and increase the risk of carcinogenesis. Multiple unrepaired DSBs account for large-sized foci in repair-deficient neurons, thus quantifying foci alone may underestimate extent and complexity of persistent DNA damage. Clin Cancer Res; 22(21); 5300-11. (c)2016 AACR. PMID- 27199495 TI - Probable Drug Interaction Between Everolimus and Clarithromycin. PMID- 27199494 TI - Clinical Validation of R-T Estimation for CoaguChek XS INR Results. AB - BACKGROUND: Despite the emergence of several new oral anticoagulants, warfarin remains a widely used form of anticoagulation that continues to have a role in the treatment of cardiac and thrombotic conditions. OBJECTIVE: The goal of this study was to evaluate whether the R-T estimation, an equation developed in a previous study, was a valid clinical tool in managing patients' warfarin therapy in an anticoagulation clinic in lieu of obtaining a venipuncture international normalized ratio (INR) secondary to a high CoaguChek XS (CXS) INR. METHODS: This study used a randomized double-blind method to compare the clinical decisions made using venipuncture or CXS machine and recorded the INR, percentage dose change, time to clinical decision from check-in, and scheduled follow-up. RESULTS: In the analysis of the difference in percentage dose change, a 1.0% (95% CI = -0.78 to 2.68; P = 0.27) difference was observed overall, and a 1.2% (95% CI = -0.59 to 2.95; P = 0.18) difference was observed in the 4 to 5.9 subgroup. Clinical decisions were reached 17 minutes faster (95% CI = 11-24; P < 0.001) overall and 17 minutes faster (95% CI = 10-24; P < 0.001) in the 4 to 5.9 subgroup. Scheduled follow-up was 0.38 weeks sooner (95% CI = 0.01-0.67; P = 0.014) overall and 0.36 weeks sooner (95% CI = 0-0.66; P = 0.041) in the 4 to 5.9 subgroup. CONCLUSIONS: The results of this study support the use of the R-T estimation for correction of INR values obtained using the CXS meter when the INR is in the range of 4 to 5.9. This correction will allow clinics using this device to more efficiently manage patients taking warfarin. PMID- 27199496 TI - Physicochemical Stability Study of Polymyxin B in Various Infusion Solutions for Administration to Critically Ill Patients. PMID- 27199498 TI - Prediction Policy Problems. PMID- 27199497 TI - Buprenorphine Versus Methadone for Opioid Dependence in Pregnancy. AB - OBJECTIVE: To evaluate maternal and neonatal safety outcomes for methadone and buprenorphine in the obstetric population. DATA SOURCES: A literature search of PubMed (1966 to March 2016) and EMBASE (1973 to March 2016) was completed using the search terms buprenorphine, methadone, pregnancy, opioid, and neonatal abstinence syndrome Priority was given to randomized controlled trials and trials directly comparing buprenorphine and methadone during pregnancy. The bibliographies were reviewed for other relevant articles. STUDY SELECTION AND DATA EXTRACTION: All human studies published in English, that compared methadone and buprenorphine use in pregnancy were evaluated. Because of the limited number of obstetric studies, only 5 critical studies were found. DATA SYNTHESIS: Buprenorphine significantly improved or had similar outcomes to methadone for development of neonatal abstinence syndrome (NAS), percentage of infants requiring treatment for NAS (20%-47% vs 45.5%-57%, respectively), total amount of morphine used to treat NAS (0.472-3.4 vs 1.862-10.4 mg, respectively), duration of NAS (4.1-5.6 vs 5.3-9.9 days, respectively), peak NAS (3.9-11 vs 4.9-12.8 score, respectively), infant hospital stay (6.8-10.6 vs 8.1-17.5 days, respectively), and gestational age at delivery (38.8-39.7 vs 37.9-38.8 weeks, respectively). No difference was found with other neonatal or maternal outcomes. CONCLUSIONS: Both methadone and buprenorphine are effective agents, with improved safety compared with continued nonmedical opioid use during pregnancy. There is evidence to suggest that buprenorphine should be considered as an equivalent option to methadone for use in pregnancy; however, larger studies are still needed to fully evaluate buprenorphine safety and advantages over methadone in the obstetric population. PMID- 27199499 TI - Maternal Education and the Link between Birth Timing and Children's School Readiness. AB - OBJECTIVE: This study explored whether mothers' education magnified the benefits of their fertility delays for their children. METHODS: Multiple-group path modeling assessed whether and why the positive association between mothers' age at first birth and children's test scores was greater for children of college educated women than children of other women. RESULTS: Older age at first birth was associated with higher math and reading test scores among the children of college educated women via their mothers' higher income and cognitive support for children. These mediational paths were less pronounced among the children of high school educated women and were not observed among the children of high school dropouts. CONCLUSION: The potential for women's delayed fertility to have benefits for their children's early educational experiences depended on their own educational attainment. PMID- 27199500 TI - Measuring the Effects of Reading Assistance Dogs on Reading Ability and Attitudes in Elementary Schoolchildren. AB - : Reading Education Assistance Dogs (R.E.A.D.) is a reading program that uses therapy dogs to increase a child's desire and ability to read. However, more data is needed to demonstrate the effectiveness of such programs. A five-week R.E.A.D. program was implemented to assess feasibility and effectiveness. Participants included 18 children entering the 2nd grade (9 assigned to read to dogs and 9 assigned to read without dogs present). Fifteen children completed the study (9 in the Dog Group and 6 in the Control Group; p = 0.058). To detect changes in reading ability and in attitudes toward reading, a Curriculum Based Measurement (CBM) for reading and an Elementary Reading Attitude Survey (ERAS) was given at week 0 and week 5. There were no significant differences over the course of the study in ERAS scores for the Dog Group, but the Control Group had significant reductions in the ERAS academic score (p = 0.04) and a trend for a reduction in the ERAS total score (p = 0.06). There was a numerically larger but not statistically different reduction in CBM in the Control Group compared to the Dog Group (p = 0.16). Further studies are warranted to determine if these trends represent statistically significant effects of the R.E.A.D. PROGRAM: PMID- 27199501 TI - Segmentation and labeling of the ventricular system in normal pressure hydrocephalus using patch-based tissue classification and multi-atlas labeling. AB - Normal pressure hydrocephalus (NPH) affects older adults and is thought to be caused by obstruction of the normal flow of cerebrospinal fluid (CSF). NPH typically presents with cognitive impairment, gait dysfunction, and urinary incontinence, and may account for more than five percent of all cases of dementia. Unlike most other causes of dementia, NPH can potentially be treated and the neurological dysfunction reversed by shunt surgery or endoscopic third ventriculostomy (ETV), which drain excess CSF. However, a major diagnostic challenge remains to robustly identify shunt-responsive NPH patients from patients with enlarged ventricles due to other neurodegenerative diseases. Currently, radiologists grade the severity of NPH by detailed examination and measurement of the ventricles based on stacks of 2D magnetic resonance images (MRIs). Here we propose a new method to automatically segment and label different compartments of the ventricles in NPH patients from MRIs. While this task has been achieved in healthy subjects, the ventricles in NPH are both enlarged and deformed, causing current algorithms to fail. Here we combine a patch-based tissue classification method with a registration-based multi-atlas labeling method to generate a novel algorithm that labels the lateral, third, and fourth ventricles in subjects with ventriculomegaly. The method is also applicable to other neurodegenerative diseases such as Alzheimer's disease; a condition considered in the differential diagnosis of NPH. Comparison with state of the art segmentation techniques demonstrate substantial improvements in labeling the enlarged ventricles, indicating that this strategy may be a viable option for the diagnosis and characterization of NPH. PMID- 27199502 TI - Simultaneous Segmentation of Retinal Surfaces and Microcystic Macular Edema in SDOCT Volumes. AB - Optical coherence tomography (OCT) is a noninvasive imaging modality that has begun to find widespread use in retinal imaging for the detection of a variety of ocular diseases. In addition to structural changes in the form of altered retinal layer thicknesses, pathological conditions may also cause the formation of edema within the retina. In multiple sclerosis, for instance, the nerve fiber and ganglion cell layers are known to thin. Additionally, the formation of pseudocysts called microcystic macular edema (MME) have also been observed in the eyes of about 5% of MS patients, and its presence has been shown to be correlated with disease severity. Previously, we proposed separate algorithms for the segmentation of retinal layers and MME, but since MME mainly occurs within specific regions of the retina, a simultaneous approach is advantageous. In this work, we propose an automated globally optimal graph-theoretic approach that simultaneously segments the retinal layers and the MME in volumetric OCT scans. SD-OCT scans from one eye of 12 MS patients with known MME and 8 healthy controls were acquired and the pseudocysts manually traced. The overall precision and recall of the pseudocyst detection was found to be 86.0% and 79.5%, respectively. PMID- 27199503 TI - Voxel Based Morphometry in Optical Coherence Tomography: Validation & Core Findings. AB - Optical coherence tomography (OCT) of the human retina is now becoming established as an important modality for the detection and tracking of various ocular diseases. Voxel based morphometry (VBM) is a long standing neuroimaging analysis technique that allows for the exploration of the regional differences in the brain. There has been limited work done in developing registration based methods for OCT, which has hampered the advancement of VBM analyses in OCT based population studies. Following on from our recent development of an OCT registration method, we explore the potential benefits of VBM analysis in cohorts of healthy controls (HCs) and multiple sclerosis (MS) patients. Specifically, we validate the stability of VBM analysis in two pools of HCs showing no significant difference between the two populations. Additionally, we also present a retrospective study of age and sex matched HCs and relapsing remitting MS patients, demonstrating results consistent with the reported literature while providing insight into the retinal changes associated with this MS subtype. PMID- 27199504 TI - Prognostic and Clinicopathological Significance of Downregulated p16 Expression in Patients with Bladder Cancer: A Systematic Review and Meta-Analysis. AB - p16, encoded by the CDKN2A gene, is a tumor suppressor that has been widely studied in cancer research. However, the relationship of p16 with prognostic and clinicopathological parameters in patients with bladder cancer remains unclear. Data inclusion criteria were articles reporting on the relationship between p16 expression and the prognosis or clinicopathology in patients with bladder cancer. Meta-analyses were performed with Stata software. Hazard ratios (HRs) or odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated to evaluate the relative risks. The source of heterogeneity was analyzed by subgroup analysis. A total of 37 studies with 2246 cases were included and analyzed. The results identified an important link between downregulated p16 expression and poor prognosis in patients with bladder cancer in terms of recurrence-free survival (RFS), overall survival (OS), progression-free survival (PFS), and some clinicopathological parameters including clinical staging, pathological degree, and lymph node metastasis. Subgroup analysis also showed that low p16 expression could function as a warning sign for RFS and PFS in patients with early-stage (Ta T1) bladder cancer. In conclusion, p16 might play an essential role in the deterioration of bladder cancer and could serve as a biomarker for the prediction for patients' progression and prognosis. PMID- 27199507 TI - Correlation of A2bAR and KLF4/KLF15 with Obesity-Dyslipidemia Induced Inflammation in Uygur Population. AB - In this paper, the researchers collected visceral adipose tissue from the Uygur population, which were divided into two groups: the normal control group (NC, n = 50, 18.0 kg/m(2) <= BMI <= 23.9 kg/m(2)) and the obese group (OB, n = 45, BMI >= 28 kg/m(2)), and then use real-time PCR to detect the mRNA expression level of key genes involved in inflammation signaling pathway. The findings suggest that, in obese status, the lower expression level of A2bAR, KLF4, and KLF15 of visceral adipose tissue may correlate with obese-dyslipidemia induced inflammation in Uygur population. PMID- 27199505 TI - Rumination and Cognitive Distraction in Major Depressive Disorder: An Examination of Respiratory Sinus Arrhythmia. AB - Difficulty regulating emotions following stressful events is a hallmark of Major Depressive Disorder (MDD). Although individuals' ability to regulate their emotions is believed to have direct consequences for both emotional and physical wellbeing, few studies have examined the cardiovascular effects of different emotion regulation strategies in MDD. To the best of our knowledge, the current study is the first to examine the effects of two emotion regulation strategies, cognitive distraction and rumination, on both self-reported sadness and respiratory sinus arrhythmia (RSA) in individuals with MDD and healthy controls (CTLs). Following a forced-failure stressor, participants were randomly assigned to a rumination or cognitive distraction condition. As expected, rumination increased sadness and triggered RSA withdrawal for both MDDs and CTLs. Interestingly, although cognitive distraction reduced sadness, it also triggered RSA withdrawal. Moreover, cognitive distraction was associated with greater RSA withdrawal for MDDs than CTLs. Thus, although depressed individuals are able to use cognitive distraction to emotionally recover from stress, it may be associated with greater cognitive effort. Adding low-cost physiological measures such as RSA into assessments has the potential to offer new and important information about the effects of emotion regulation on mental and physiological health. PMID- 27199508 TI - Th17 Cytokines and Barrier Functions. PMID- 27199506 TI - Nonessential Role for the NLRP1 Inflammasome Complex in a Murine Model of Traumatic Brain Injury. AB - Traumatic brain injury (TBI) elicits the immediate production of proinflammatory cytokines which participate in regulating the immune response. While the mechanisms of adaptive immunity in secondary injury are well characterized, the role of the innate response is unclear. Recently, the NLR inflammasome has been shown to become activated following TBI, causing processing and release of interleukin-1beta (IL-1beta). The inflammasome is a multiprotein complex consisting of nucleotide-binding domain and leucine-rich repeat containing proteins (NLR), caspase-1, and apoptosis-associated speck-like protein (ASC). ASC is upregulated after TBI and is critical in coupling the proteins during complex formation resulting in IL-1beta cleavage. To directly test whether inflammasome activation contributes to acute TBI-induced damage, we assessed IL-1beta, IL-18, and IL-6 expression, contusion volume, hippocampal cell death, and motor behavior recovery in Nlrp1(-/-), Asc(-/-), and wild type mice after moderate controlled cortical impact (CCI) injury. Although IL-1beta expression is significantly attenuated in the cortex of Nlrp1(-/-) and Asc(-/-) mice following CCI injury, no difference in motor recovery, cell death, or contusion volume is observed compared to wild type. These findings indicate that inflammasome activation does not significantly contribute to acute neural injury in the murine model of moderate CCI injury. PMID- 27199509 TI - Correlation between Serum Osteopontin and miR-181a Levels in Allergic Rhinitis Children. AB - BACKGROUND: Osteopontin (OPN) has been proved to be associated with allergic airway inflammation. However, the roles of OPN and its regulation in childhood allergic rhinitis (AR) are poorly understood. OBJECTIVE: This study aims to evaluate the expression of OPN and miR-181a in children with AR and their association with Th1/Th2 immune response. METHODS: Children who suffered from AR were included along with control subjects. Serum was collected to examine the level of OPN and Th1/Th2 cytokines by enzyme-linked immunosorbent assay (ELISA) and the level of miR-181a by quantitative polymerase chain reaction (qPCR). RESULTS: Children with AR had significantly higher serum levels of OPN and lower serum levels of miR-181a than healthy controls. Furthermore, serum levels of OPN were positively correlated with Th2 cytokine and negatively correlated with Th1 cytokine. On the contrary, miR-181a level had a negative correlation with IL-4/IL 5 and positive correlation with IFN-gamma/IL-12. More importantly, there was also significant negative correlation between OPN and miR-181a. CONCLUSION: The OPN protein and miR-181a levels may serve as predictors of disease severity in childhood AR and appear to be promising targets for modulating AR. PMID- 27199510 TI - Icariin Prevents Cartilage and Bone Degradation in Experimental Models of Arthritis. AB - BACKGROUND: Icariin (ICA) is an active compound extracted from Epimedium brevicornum Maxim. Previous reports have shown that icariin has a clinically significant therapeutic effect on rheumatoid arthritis. However, little is known about the mechanism by which icariin inhibits cartilage and bone degradation. METHODS: New Zealand rabbits were immunized with antigen-induced arthritis (AIA) and treated with icariin. Joint tissues from rabbits were studied by histological analysis, transmission electron microscopy (TEM), and micro-CT. The expression levels of receptor activator of nuclear factor-B ligand (RANKL) and osteoprotegerin (OPG) in joint tissues were determined using immunohistochemistry and real-time PCR analysis. RESULTS: Histological analysis and TEM sections of cartilage in the ICA treated group showed a low level of chondrocyte destruction. Micro-CT analysis showed that the bone mineral density value and bone structural level in ICA treated rabbits were significantly higher compared with those in the AIA group. Immunohistochemistry and real-time PCR analysis showed that icariin treatment reduced RANKL expression and enhanced OPG expression levels, as compared to the AIA group. CONCLUSION: These data indicate that ICA suppresses articular bone loss and prevents joint destruction. This study also determined that ICA regulated articular bone loss in part by regulating RANKL and OPG expression. PMID- 27199511 TI - Is current clinical practice modified about intraoperative breast irradiation? AB - After the results obtained in the two randomized clinical trial, the ELIOT trial and the TARGIT-A trial, a heated debate is going on concerning the question of applying intraoperative radiotherapy (IORT) instead of postoperative whole breast irradiation (WBI) after breast conservative treatment. Currently, many centers are applying the IORT following the strict selection criteria dictated by the working groups American Society for Radiation Oncology (ASTRO) and Groupe Europeen de Curietherapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) and monitoring the oncological outcome together with radiation toxicity on breast tissue. The clinical experience of the Geneva University Hospital regarding the use of the Intrabeam system is evaluated and compared with current evidences. PMID- 27199513 TI - Tumor response assessment by the single-lesion measurement per organ in small cell lung cancer. AB - BACKGROUND: The criterion of two target lesions per organ in the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 is an arbitrary one, being supported by no objective evidence. The optimal number of target lesions per organ still needs to be investigated. We compared tumor responses using the RECIST 1.1 (measuring two target lesions per organ) and modified RECIST 1.1 (measuring the single largest lesion in each organ) in patients with small cell lung cancer (SCLC). METHODS: We reviewed medical records of patients with SCLC who received first-line treatment between January 2004 and December 2014 and compared tumor responses according to the two criteria using computed tomography. RESULTS: There were a total of 34 patients who had at least two target lesions in any organ according to the RECIST 1.1 during the study period. The differences in the percentage changes of the sum of tumor measurements between RECIST 1.1 and modified RECIST 1.1 were all within 13%. Seven patients showed complete response and fourteen showed partial response according to the RECIST 1.1. The overall response rate was 61.8%. When assessing with the modified RECIST 1.1 instead of the RECIST 1.1, tumor responses showed perfect concordance between the two criteria (k=1.0). CONCLUSIONS: The modified RECIST 1.1 showed perfect agreement with the original RECIST 1.1 in the assessment of tumor response of SCLC. Our result suggests that it may be enough to measure the single largest target lesion per organ for evaluating tumor response. PMID- 27199512 TI - Risk prediction models for hepatocellular carcinoma in different populations. AB - Hepatocellular carcinoma (HCC) is a malignant disease with limited therapeutic options due to its aggressive progression. It places heavy burden on most low and middle income countries to treat HCC patients. Nowadays accurate HCC risk predictions can help making decisions on the need for HCC surveillance and antiviral therapy. HCC risk prediction models based on major risk factors of HCC are useful and helpful in providing adequate surveillance strategies to individuals who have different risk levels. Several risk prediction models among cohorts of different populations for estimating HCC incidence have been presented recently by using simple, efficient, and ready-to-use parameters. Moreover, using predictive scoring systems to assess HCC development can provide suggestions to improve clinical and public health approaches, making them more cost-effective and effort-effective, for inducing personalized surveillance programs according to risk stratification. In this review, the features of risk prediction models of HCC across different populations were summarized, and the perspectives of HCC risk prediction models were discussed as well. PMID- 27199514 TI - Patterns of antiemetic prophylaxis for chemotherapy-induced nausea and vomiting in China. AB - BACKGROUND: Few studies have attempted to evaluate the use of antiemetic therapy for chemotherapy-induced nausea and vomiting (CINV) at a national level in China or to assess how treatment regimens adhere to current guidelines. METHODS: We searched the China Health Insurance Research Association (CHIRA) Database to identify patients with cancer who were >=18 years old and received either moderately or highly emetogenic chemotherapy (MEC and HEC, respectively) between 2008 and 2012. Patients' characteristics as well as usage of specific antiemetic regimens were analyzed using descriptive statistics. RESULTS: Of the 14,548 patients included in the study, 6,477 received HEC while 8,071 were treated with MEC. Approximately 89.9% used antiemetics prophylactically to prevent acute CINV and 71.5% for delayed CINV while 9.0% were prescribed antiemetics as rescue therapy. A significantly lower proportion of patients treated with HEC received prophylactic antiemetic therapy for delayed CINV as compared to those treated with MEC (59.4% vs. 81.3%; P<0.001). The HEC group had a slightly lower proportion of patients using a mixed regimen containing a 5-HT3 antagonist to prevent both acute and delayed CINV than the MEC group (P<=0.012); however, a higher proportion received a mixed regimen containing corticosteroids (P<=0.007). Although more than half of the patients in the HEC group took three antiemetics to prevent acute and delayed CINV, these rates were significantly lower than those of the MEC group (both P<0.001). Finally, analysis of the regimens used revealed that there is over-utilization of drugs within the same class of antiemetic. CONCLUSIONS: These findings indicate that more attention is needed for treatment of delayed CINV, in terms of both overall use and the components of a typical treatment regimen. PMID- 27199515 TI - Parasympathetic neurogenesis is strongly associated with tumor budding and correlates with an adverse prognosis in pancreatic ductal adenocarcinoma. AB - OBJECTIVE: To investigate the frequency of parasympathetic neurogenesis and determine its association with tumor budding and prognosis in pancreatic ductal adenocarcinoma (PDAC). METHODS: Parasympathetic neurogenesis was defined as the distribution of abnormal parasympathetic nerves in the stroma tissue. Staining of vesicular acetylcholine transporter (VAChT), as a marker for parasympathetic neurogenesis, was performed on a representative specimen of the tumor for 59 PDAC patients with available clinical, pathologic, and follow-up information. Three specimens containing normal pancreatic tissues were stained in parallel. The number of parasympathetic nerve fibers was counted in five high-power microscopic fields (5*0.785 mm(2)). Cut-off values were calculated by receiver operating characteristic curve analysis. RESULTS: VAChT-positive parasympathetic nerve fibers were not seen in the stroma of 3 cases of normal pancreatic tissues. In 59 PDAC cases, the range of parasympathetic neurogenesis was 4-38 fibers/(5*0.785) mm(2), with a median of 18 fibers/(5*0.785) mm(2). Patients with parasympathetic neurogenesis >15 fibers/(5*0.785) mm(2) were defined as the high-density group (39 patients, 66.1%), and those with parasympathetic neurogenesis 15 fibers/(5*0.785) mm(2) as the low-density group (20 patients, 33.9%). The high density group had a higher occurrence of tumor budding (P=0.001) and a higher rate of early recurrence (P=0.035). Parasympathetic neurogenesis appeared to be an independent adverse prognostic factor [hazard ratio (HR)=2.45, 95% confidence interval (95% CI): 1.25-4.81, P=0.009], in addition to American Joint Committee on Cancer (AJCC) stage (P=0.010) and tumor budding (P=0.009). CONCLUSIONS: Parasympathetic neurogenesis is strongly associated with tumor budding and correlates with an adverse prognosis in PDAC. PMID- 27199516 TI - Comparison of the short-term and long-term outcomes of laparoscopic hysterectomies and of abdominal hysterectomies: a case study of 4,895 patients in the Guangxi Zhuang Autonomous Region, China. AB - BACKGROUND: To evaluate the short-term and long-term outcomes after laparoscopic hysterectomy (LH) compared with abdominal hysterectomy (AH) in case of benign gynecological disease. METHODS: A multi-center cohort retrospective comparative study of population among 4,895 hysterectomies (3,539 LH vs.1,356 AH) between 2007 and 2013 was involved. Operative time (OT), estimated blood loss (EBL), intra-operative and post-operative complications, passing flatus; days with indwelling catheter, questionnaires covering pelvic floor functions and sexual functions were assessed. RESULTS: The EBL (174.1+/-157.4 vs. 263.1+/-183.2 cc, LH and AH groups, respectively), passing flatus (38.7+/-14.1 vs. 48.1+/-13.2 hours), days with indwelling catheter (1.5+/-0.6 vs. 2.2+/-0.8 days), use of analgesics (6.5% vs. 73.1%), intra-operative complication rate (2.4% vs. 4.1%), post operative complication rate (2.3% vs. 5.7%), post-operative constipation (12.1% vs. 24.6%), mild and serious stress urinary incontinence (SUI) post-operative (P<0.001; P=0.014), and proportion of Female Sexual Functioning Index (FSFI) total score <26.55 post-operative (P<0.001) of the LH group were significantly less than those of AH group. There were no significant differences in OT (106.5+/ 34.5 vs. 106.2+/-40.3 min) between the two groups. CONCLUSIONS: LH is a safe and efficient operation for improving patients?long-term quality of life (QoL), and LH is a cost-effectiveness procedure for treating benign gynecological disease. LH is superior to AH due to reduced EBL, reduced post-operative pain and earlier passing flatus. PMID- 27199517 TI - Phase I study of chimeric anti-CD20 monoclonal antibody in Chinese patients with CD20-positive non-Hodgkin's lymphoma. AB - OBJECTIVE: This study was designed to determine the safety, pharmacokinetics and biologic effects of a human-mouse chimeric anti-CD20 monoclonal antibody (SCT400) in Chinese patients with CD20-positive B-cell non-Hodgkin's lymphoma (CD20(+) B cell NHL). SCT400 has an identical amino acid sequence as rituximab, with the exception of one amino acid in the CH1 domain of the heavy chain, which is common in Asians. METHODS: Fifteen patients with CD20(+) B-cell NHL received dose escalating SCT400 infusions (250 mg/m(2): n=3; 375 mg/m(2): n=9; 500 mg/m(2): n=3) once weekly for 4 consecutive weeks with a 24-week follow-up period. The data of all patients were collected for pharmacokinetics and pharmacodynamics analyses. RESULTS: No dose-limiting toxicities were observed. Most drug-related adverse events were grade 1 or 2. Two patients had grade 3 or 4 neutropenia. Under premedication, the drug-related infusion reaction was mild. A rapid, profound and durable depletion of circulating B cells was observed in all dose groups without significant effects on T cell count, natural killer (NK) cell count or immunoglobulin levels. No patient developed anti-SCT400 antibodies during the course of the study. SCT400 serum half-life (T1/2), maximum concentration (Cmax) and area under the curve (AUC) generally increased between the first and fourth infusions (P<0.05). At the 375 mg/m(2) dose, the T1/2 was 122.5+/-46.7 h vs. 197.0+/-75.0 h, respectively, and the Cmax was 200.6+/-20.2 g/mL vs. 339.1+/-71.0 g/mL, respectively. From 250 mg/m(2) to 500 mg/m(2), the Cmax and AUC increased significantly in a dose-dependent manner (P<0.05). Patients with a high tumor burden had markedly lower serum SCT400 concentrations compared with those without or with a low tumor burden. Of the 9 assessable patients, 1 achieved complete response and 2 achieved partial responses. CONCLUSIONS: SCT400 is well-tolerated and has encouraging preliminary efficacy in Chinese patients with CD20(+) B-cell NHL. PMID- 27199519 TI - Evolution of radical hysterectomy for cervical cancer along the last two decades: single institution experience. AB - BACKGROUND: The radical hysterectomy (RH) surgical technique has improved along the years. It is used for the treatment of cervical cancer, endometrial cancer when affecting the cervix, and upper vaginal carcinomas. Our aim was to describe the historical evolution of the technique after the introduction of laparoscopy at our institution. METHODS: We performed a retrospective review of medical records of patients who underwent RH, grouped in three periods according to the year of surgery: 1990-1999, 2000-2009 and 2010-2013. Patients?characteristics, pathologic details, intraoperative and postoperative complications were analyzed and compared throughout the time periods. RESULTS: A total of 102 cases of RH were performed at our center during the study period. Among all data collected, the presence of necrosis, age, number of lymph nodes, surgery route, operating time, hospital stay, blood loss and transfusion requirement were statistically significant different among groups. Conversion to laparotomy rate was 19% for the second period compared to the absence of cases in the last one. No significant differences (P=0.124) were observed in the adjuvant treatment received among the three different groups. At the time of the last contact the patients free of disease were 12 (85.7%), 53 (91.3%) and 26 (86.6%) respectively (P=0.406). Regarding the disease-free interval, we found significant better outcomes in the group of laparotomy compared to laparoscopy (P=0.015). CONCLUSIONS: Laparoscopic RH is an acceptable surgery with advantages like magnified vision of the operation field, lower surgical complications, shorter hospital stay and earlier resumption to daily activities. PMID- 27199518 TI - Clinical and functional comparison of endoprosthetic replacement with intramedullary nailing for treating proximal femur metastasis. AB - OBJECTIVE: To evaluate the clinical and functional outcomes of modular endoprosthetic replacement (EPR) compared to proximal femur intramedullary nailing (IMN) for the treatment of proximal femur metastases. METHODS: We retrospectively studied the records of patients with proximal femur metastatic lesions treated with surgical stabilization between January 2007 and December 2014 in terms of operation time, blood loss, postoperative score, soreness, Karnofsky performance score (KPS) and survival time. RESULTS: There were 34 patients treated with surgical stabilization. The mean follow-up period was 12.1?.6 months (range: 10-47 months). Thirteen were treated with EPR and 21 were stabilized with IMN (20 males, 14 females; mean age: 68.7 years). The median survival time was 11.0 months for both groups (P=0.147). The operation time, blood loss and Harris score of IMN group were lower than those of EPR group (P=0.001, P=0.001, P=0.002, respectively). CONCLUSIONS: Both EPR and IMN for treating proximal femur metastasis achieved effective clinical outcomes. Therefore, the suitable surgical methods depended on the general conditions and medical requirements of patients, as well as the technical advantages of the doctor. PMID- 27199520 TI - Concurrent chemoradiotherapy for cervical cancer: background including evidence based data, pitfalls of the data, limitation of treatment in certain groups. AB - Concurrent chemoradiotherapy (CCRT) is regarded as the standard treatment for locally advanced uterine cervical cancer (LACC), including stage Ib2-IVa disease [International Federation of Gynecology and Obstetrics (FIGO) staging]. However, approximately a third of eligible patients in previous studies died of LACC despite receiving CCRT. The therapeutic significance of CCRT alone in stage III IVa disease has not yet been confirmed. Effective treatment of some LACC is beyond the scope of CCRT. The objective of the present review is to highlight some challenging work aimed at overcoming this seemingly intractable disease. CCRT with increased peak concentrations of cisplatin (CDDP), surgery following CCRT, adjuvant chemotherapy (CT) following CCRT, and neoadjuvant CT followed by CCRT are strategies expected to enhance the therapeutic efficacy of CCRT. If patients with LACC were divided into those with low-risk or high-risk systemic disease or prognoses, novel strategies should be assessed in the group with high risk disease. PMID- 27199522 TI - Neoadjuvant chemotherapy for locally advanced cervical cancer. AB - Neoadjuvant chemotherapy followed by surgery (NCS) has not been fully evaluated clinically. Currently, the main regimen of neoadjuvant chemotherapy (NAC) used in NCS includes cisplatin. The antitumor effects of NAC reduce lymph node metastasis and the tumor diameter in patients prior to surgery, and this can reduce the number of high risk patients who require postoperative radiation therapy. Many randomized controlled trials (RCTs) have examined the long-term prognosis of NCS compared to primary surgery, but the utility of NCS remains uncertain. The advent of concurrent chemoradiotherapy (CCRT) has markedly improved the outcome of radiotherapy (RT), and CCRT is now used as a standard method in many cases of advanced bulky cervical cancer. NCS gives a better treatment outcome than radiation therapy alone, but it is important to verify that NCS gives a similar or better outcome compared to CCRT. PMID- 27199521 TI - Adjuvant chemotherapy for early-stage cervical cancer. AB - The aim of this review is to address the current status of adjuvant chemotherapy alone in early-stage cervical cancer treatments in the literature. At present, the therapeutic effect of adjuvant chemotherapy alone after radical surgery (RS) has not yet been established, and radiation therapy (RT) or concurrent chemoradiotherapy (CCRT) is recommended as the standard adjuvant therapy after RS for early-stage cervical cancer in various guidelines. The main purpose of adjuvant therapy after RS, however, should be to reduce extrapelvic recurrence rather than local recurrence, although adjuvant RT or CCRT has survival benefits for patients with intermediate- or high-risk factors for recurrence. Moreover, several studies reported that adjuvant therapies including RT were associated with a higher incidence of complications, such as lymphedema, bowel obstruction and urinary disturbance, and a lower grade of long-term quality of life (QOL) or sexual functioning than adjuvant chemotherapy alone. The effect of adjuvant chemotherapy alone for early-stage cervical cancer with intermediate- or high risk factors for recurrence were not fully investigated in prospective studies, but several retrospective studies suggest that the adjuvant effects of chemotherapy alone are at least similar to that of RT or CCRT in terms of recurrence rate, disease-free survival, or overall survival (OS) with lower incidence of complications. Whereas cisplatin based combination regimens were used in these studies, paclitaxel/cisplatin (TP) regimen, which is currently recognized as a standard chemotherapy regimen for patients with metastatic, recurrent or persistent cervical cancer by Gynecologic Oncology Group (GOG), had also survival benefit as an adjuvant therapy. Therefore, it may be worth considering a prospective randomized controlled trial (RCT) of adjuvant chemotherapy alone using TP regimen versus adjuvant RT as an alternative adjuvant therapy. Because early-stage cervical cancer is a curable condition, it is necessary that the therapeutic strategies should be improved with considering adverse events and QOL for long-term survivors. PMID- 27199524 TI - Metformin for treatment of clozapine-induced weight gain in adult patients with schizophrenia: a meta-analysis. AB - BACKGROUND: Long-term use of clozapine for individuals with schizophrenia carries a high risk for developing metabolic abnormalities, especially clozapine-induced weight gain. Previous studies suggest that metformin can decrease clozapine induced weight gain, but the sample sizes of most of these studies are relatively small. METHODS: We identified randomized controlled trials (RCTs) published prior to December 15, 2015 about the use of metformin to treat clozapine-induced weight gain in adults with schizophrenia by searching several English-language and Chinese-language databases. Two independent researchers did the screening and data extraction. We used Revman 5.3 to conduct the meta-analyses, assessed the risk of bias (RoB), and assessed the strength of the evidence using the Cochrane Grades of Recommendation, Assessment, Development, and Evaluation (GRADE). RESULTS: Six studies with a pooled sample of 207 treatment-group patients and 207 control-group patients were included -- three double-blind, placebo-controlled RCTs and three RCTs that did not use placebo controls and were not blinded. The meta-analysis found that compared to the control condition, patients receiving metformin experienced significantly greater reductions in body weight (mean difference [MD]=-2.89 kg, 95% CI: -4.20 to -1.59 kg) and body mass index (BMI) (MD=-0.81, 95% CI: -1.16 to -0.45), but there was no significant difference between the groups in the prevalence of side effects. Based on the GRADE scale, the strength of the evidence for the change in weight outcome was 'moderate' and that for the change in BMI outcome was 'high', but the strength of evidence about differences in side effects between groups was 'low' or 'very low'. CONCLUSIONS: Adjunctive treatment with metformin appears to be effective for treating clozapine-induced weight gain and elevations in BMI in adult patients with schizophrenia. However, the quality of the evidence about the safety of this treatment is low, follow-up time in the available studies is relatively short, and half of the studies did not employ blinded assessment of outcome measures. Larger studies with placebo controls that follow patients for at least 24 weeks and that make blinded assessments of a range of relevant outcome measures (weight, BMI, blood lipids, insulin resistance, etc.) are needed to confirm these results. PMID- 27199523 TI - Chemotherapy and molecular targeting therapy for recurrent cervical cancer. AB - For patients with primary stage IVB, persistent, or recurrent cervical cancer, chemotherapy remains the standard treatment, although it is neither curative nor associated with long-term disease control. In this review, we summarized the history of treatment of recurrent cervical cancer, and the current recommendation for chemotherapy and molecular targeted therapy. Eligible articles were identified by a search of the MEDLINE bibliographical database for the period up to November 30, 2014. The search strategy included the following any or all of the keywords: "uterine cervical cancer", "chemotherapy", and "targeted therapies". Since cisplatin every 21 days was considered as the historical standard treatment for recurrent cervical cancer, subsequent trials have evaluated and demonstrated activity for other agents including paclitaxel, gemcitabine, topotecan and vinorelbine among others. Accordingly, promising agents were incorporated into phase III trials. To examine the best agent to combine with cisplatin, several landmark phase III clinical trials were conducted by Gynecologic Oncology Group (GOG) and Japan Clinical Oncology Group (JCOG). Through, GOG204 and JCOG0505, paclitaxel/cisplatin (TP) and paclitaxel/carboplatin (TC) are now considered to be the recommended therapies for recurrent cervical cancer patients. However, the prognosis of patients who are already resistant to chemotherapy, are very poor. Therefore new therapeutic strategies are urgently required. Molecular targeted therapy will be the most hopeful candidate of these strategies. From the results of GOG240, bevacizumab combined with TP reached its primary endpoint of improving overall survival (OS). Although, the prognosis for recurrent cervical cancer patients is still poor, the results of GOG240 shed light on the usefulness of molecular target agents to chemotherapy in cancer patients. Recurrent cervical cancer is generally considered incurable and current chemotherapy regiments offer only modest gains in OS, particularly for patients with multiple poor prognostic factors. Therefore, it is crucial to consider not only the survival benefit, but also the minimization of treatment toxicity, and maximization of quality of life (QOL). PMID- 27199525 TI - Comparison of the density of gamma-aminobutyric acid in the ventromedial prefrontal cortex of patients with first-episode psychosis and healthy controls. AB - BACKGROUND: Abnormality in the concentration and functioning of gamma aminobutyric acid (gamma-aminobutyric acid, GABA) in the brain is not only an important hypothetical link to the cause of schizophrenia but it may also be correlated with the cognitive decline and negative symptoms of schizophrenia. Studies utilizing high field magnetic resonance spectroscopy (MRS) report abnormal density of GABA in the ventromedial prefrontal cortex (vmPFC) of patients with chronic schizophrenia, but these results may be confounded by study participants' prior use of antipsychotic medications. AIM: Compare the density of GABA in the vmPFC of patients with first-episode psychosis to that in healthy controls and assess the relationship of GABA density in the vmPFC to the severity of psychotic symptoms. METHODS: Single-voxel (1)H-MRS was used to assess the concentration of GABA and other metabolites in the vmPFC of 22 patients with first-episode psychosis (10 with schizophrenia and 12 with schizophreniform disorder) and 23 healthy controls. Thirteen of the 22 patients were drug-naive and 9 had used antipsychotic medication for less than 3 days. The Positive and Negative Syndrome Scale (PANSS) was used to evaluate the severity of psychotic symptoms in the patient group. RESULTS: The mean (sd) GABA density in the vmPFC was significantly higher in patients than in controls (2.28 [0.54] v. 1.93 [0.32] mM, t=2.62, p=0.012). The densities of other metabolites - including N acetylaspartic acid (NAA), glutamic acid (GLU), and glutamine (GLN) - were not significantly different between patients and controls. Among the patients, GABA density in the vmPFC was not significantly correlated with PANSS total score or with any of the three PANSS subscale scores for positive symptoms, negative symptoms, and general psychopathology. GABA concentration was not associated with the duration of illness, but it was significantly correlated with patient age (r=0.47, p=0.026). CONCLUSION: Elevation of GABA density in the vmPFC of patients with first-episode psychosis confirms that this abnormality is independent of medication use. The failure to find a correlation of GABA density in the vmPFC with the severity of psychotic symptoms needs to be confirmed in larger studies, but it suggests that there are several intervening steps between brain pathology and clinical symptoms. PMID- 27199526 TI - Association of schizophrenia with the rs821633 polymorphism in the DISC1 gene among Han Chinese. AB - BACKGROUND: Previous studies report that various single nucleotide polymorphisms (SNP) in the Disrupted-in Schizophrenia 1 (DISC1) gene are closely associated with schizophrenia, but there are no studies that assess the relationship of age of onset of schizophrenia with these SNPs. OBJECTIVE: Investigate the relationship between the rs821633 SNP in the DISC1 gene and the occurrence and age of onset of schizophrenia in Han Chinese. METHODS: We used the TaqMan genotyping technology to examine the rs821633 SNP in the DISC1 gene among 315 individuals who developed schizophrenia prior to 19 years of age ('early-onset'), 407 individuals who developed schizophrenia when 19 years of age or older ('late onset'), and 482 healthy controls. We used survival analyses to investigate the relationship between the rs821633(C) risk allele and the age of onset of schizophrenia. RESULTS: Compared to the prevalence in healthy controls, the prevalence of the C/C genotype of rs821633 and of the C allele in rs821633 were significantly greater in individuals with early-onset schizophrenia (X (2)=7.17, df=1, p=0.007; X (2)=7.20, df=2, p=0.032) and significantly greater in individuals with late-onset schizophrenia (X (2)=5.36, df=1, p=0.022; X (2)=6.58, df=2, p=0.041). However, there were no significant differences in the prevalence of the C/C genotype or the C allele between individuals with early-onset and late onset schizophrenia. Kaplan-Meier survival analyses found no significant association between the rs821633(C) risk allele and age of onset in schizophrenia. CONCLUSION: We confirm the association of polymorphism in the rs821633 SNP in the DISC1 gene with schizophrenia among Han Chinese, but we found no association between the rs821633(C) risk allele and the age of onset in individuals with schizophrenia. PMID- 27199528 TI - Psychopharmacological treatment for schizophrenia: less is more. AB - Antipsychotic polypharmacy in the treatment of schizophrenia is more common in China and other Asian countries than in Western countries. The reasons for this are unclear, but it may be related to an unsubstantiated belief among clinicians that multiple medications are more likely to achieve the desired clinical outcome. Antipsychotic medications are the mainstay of treatment for individuals with schizophrenia, but the use of antipsychotic polypharmacy and of high dosages of antipsychotic medication are associated with substantially increased risks without conferring improved clinical outcomes. It is generally accepted that high dosages of antipsychotic medications and the simultaneous use of multiple antipsychotics are associated with an increased prevalence, duration, and severity of adverse drug effects. More recent evidence also suggests that antipsychotic polypharmacy and the associated high overall dosage of antipsychotic medication lead to excessive striatal D2 receptor occupation (resulting in tolerance and drug withdrawal problems) and exacerbation of the impaired synaptic plasticity seen in schizophrenia (magnifying the cognitive impairment associated with the condition). Clinicians need to apply the 'less is more' principle in the psychopharmacological treatment of schizophrenia. PMID- 27199527 TI - Comorbid anxiety and depression in school-aged children with attention deficit hyperactivity disorder (ADHD) and selfreported symptoms of ADHD, anxiety, and depression among parents of school-aged children with and without ADHD. AB - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a common psychiatric disorder in children that can extend into adulthood and that is often associated with a variety of comorbid psychiatric disorders. AIM: Assess the comorbidity of ADHD with anxiety disorders and depressive disorders in school aged children, and the relationship of the severity of ADHD, anxiety, and depressive symptoms in children who have ADHD with the severity of the corresponding symptoms in their parents. METHODS: A two-stage screening process identified children 7-10 years of age with and without ADHD treated at the Xin Hua Hospital in Shanghai. ADHD and other DSM-IV diagnoses were determined by a senior clinician using the Schedule for Affective Disorder and Schizophrenia for School-Aged Children (K-SADS-PL). One parent for each enrolled child completed three self-report scales: the ADHD Adult Self Report Scale (ASRS), the State Trait Anxiety Inventory (STAI), and the Beck Depression Inventory (BDI). In total 135 children with ADHD and 65 control group children without ADHD were enrolled; parents for 94 of the children with ADHD and 63 of the children without ADHD completed the parental assessment scales. RESULTS: Among the 135 children with ADHD, 27% had a comorbid anxiety disorder, 18% had a comorbid depressive disorder, and another 15% had both comorbid anxiety and depressive disorders. Parents of children with ADHD self-reported more severe ADHD inattention symptoms than parents of children without ADHD and were more likely to meet criteria for adult ADHD. Mothers (but not fathers) of children with ADHD had significantly more severe trait anxiety and depressive symptoms than mothers of children without ADHD. Among children with ADHD, the severity of ADHD symptoms was not significantly correlated with the severity of ADHD symptoms in parents, but depressive symptoms and anxiety symptoms in the children were significantly correlated with the corresponding symptoms in the parents. CONCLUSION: School aged children with ADHD commonly suffer from comorbid anxiety and depressive disorders, and the severity of these symptoms parallels the level of anxiety and depressive symptoms in their parents. Self-reported symptoms of ADHD are significantly more common in parents of children with ADHD than in parents of children without ADHD. Longitudinal studies are needed to disentangle the genetic, biological, and social factors responsible for these complex inter relationships. PMID- 27199529 TI - 'Less is more' in the Chinese context. AB - Excessive polypharmacy is a common problem around the world, particularly in the treatment of psychiatric disorders. In mainland China use of out-of-date treatment strategies by psychiatric professionals is one of the reasons; others include unrealistically high expectations about the effectiveness of medications, the dominant role of the doctor in doctor-patient negotiations about treatment, the practice of polypharmacy in Traditional Chinese Medicine (TCM), the profit driven nature of medical institutions and individuals, the infiltration of pharmaceutical marketing, and a critical lack of relevant research. This commentary considers the cultural factors that need to be addressed when trying to reduce polypharmacy in psychiatry in China. PMID- 27199530 TI - Case report of eosinophilia induced by quetiapine. AB - An increase in the concentration of eosinophils in blood may lead to endocarditis, myocarditis, and pericarditis. When the absolute eosinophil count increases beyond 1.5 x 10(9)/L, myocardial damage and even death can occur. This case report describes a 47-year-old male with an alcohol-induced psychotic disorder who developed eosinophilia 4 weeks after starting treatment with quetiapine 50-200 mg/d. His maximum recorded absolute eosinophil count was 7.63 x 10(9)/L (normal range < 0.5 x 10(9)/L), but the level returned to normal over a 4 week period after stopping quetiapine and no myocardial damage was observed. This patient's dramatic eosinophilia did not have any associated clinical symptoms; it was only identified as part of a routine blood test a few weeks after starting quetiapine. This is a reminder that all clinicians who treat patients with antipsychotic medications must be vigilant about the occurrence of such rare but life-threatening adverse events. PMID- 27199531 TI - Panic attacks 10 years after heart transplantation successfully treated with low dose citalopram: a case report. AB - Panic attacks are common among patients who have undergone heart transplantation, but there are no clinical guidelines for the treatment of panic attacks in this group of patients. This report describes a 22-year-old woman who experienced panic attacks 10 years after heart transplant surgery. The attacks started after she discovered that the average post-transplantation survival is 10 years. Treated with citalopram 10 mg/d, her symptoms improved significantly after 2 weeks and had completely resolved after 8 weeks. A positive physician-patient relationship with the doctors who regularly followed her medical condition was crucial to encouraging her to adhere to the treatment with citalopram. She continued taking the citalopram for 7 months without any adverse effects. When followed up 3 months after stopping the citalopram, she had had no recurrence of the panic attacks. PMID- 27199532 TI - The debate about p-values. AB - The p-value is the most widely used statistical concept in biomedical research. Recently, there are controversies over its utility and over the possible relationship between p-value misuse and the relatively high proportion of published medical research that cannot be replicated. In this paper, we introduce the p-value in layman's terms and explain its randomness and limitations. However, we also point out that the available alternatives to p-value suffer similar limitations. We conclude that using p values is a valid way to test the null and alternative hypotheses in clinical trials. However, using the p-value from a single statistical test to judge the scientific merit of a research project is a misuse of the p-value; the results of inference tests using p-values need to be integrated with secondary results and other data to arrive at clinically valid conclusions. Understanding the variability and limitations of the p-value is important for the interpretation of statistical results in research studies. PMID- 27199533 TI - Comorbid bipolar disorder and obsessive-compulsive disorder:state of the art in pediatric patients. AB - A full-text Chinese translation of this article will be available at http://dx.doi.org/10.11919/j.issn.1002-0829.215128 on April 25, 2016. PMID- 27199534 TI - Influence of Gelatin-Thrombin Matrix Tissue Sealant on Bacterial Colony Formation and Risk of Pelvic Infection. AB - Objective. Gelatin-thrombin matrix (GTM) tissue sealant use was previously identified as an independent predictor of pelvic infection following hysterectomies. We aim to elucidate contributing factors by assessing influence of GTM on bacterial colony formation and characterizing bacteria present at the vaginal cuff. Methods. Escherichia coli was incubated in phosphate-buffered saline (PBS) and pelvic washings with and without GTM to assess influence on colony formation. Pelvic washings of the vaginal cuff were collected from hysterectomies occurring from June through October 2015. In vitro techniques, 16S rRNA gene qPCR, and 16S amplicon sequencing were performed with washings to characterize bacteria at the vaginal cuff. Results. Mean bacterial colony formation in PBS was greater for E. coli incubated in the presence of GTM (1.48 * 10(7) CFU/mL) versus without (9.95 * 10(5) CFU/mL) following 20-hour incubation (p = 0.001). Out of 61 pelvic washings samples, 3 were culture positive (>=5000 CFU/mL) with Enterococcus faecalis. Conclusion. In vitro experiments support a facilitating role of GTM on colony formation of E. coli in PBS. However, given the negative results of surgical site washings following adequate disinfection, the role of GTM in promoting posthysterectomy pelvic infections may be limited. Analysis of pelvic washings revealed presence of E. faecalis, but results were inconclusive. Further studies are recommended. PMID- 27199535 TI - Magnetic resonance imaging in muscular dystrophies. PMID- 27199537 TI - Imaging alterations in skeletal muscle channelopathies: a study in 15 patients. AB - Skeletal muscle channelopathies (SMC), including non dystrophic myotonias (NDM) and periodic paralyses (PP), are characterized by considerable clinical overlap and clinical features not always allow addressing molecular diagnosis. Muscle imaging has been shown to be useful for differential diagnosis in neuromuscular disorders, however it has been relatively poorly investigated in SMC. We studied 15 patients affected by genetically confirmed SMC (NDM = 9, PP = 6) through muscle MRI or CT of thighs and legs, including 11 patients mutated in SCN4A gene, 2 in CACNA1S and 2 in CLCN1. Mean age at muscle imaging was 45.2 +/- 18 years (range 22-70). Overall, fatty infiltration was found in thigh muscles in 8 (53%) patients and in leg muscles in 10 (60%). All patients mutated in CLCN1 and CACNA1S had abnormal thigh and/or leg muscle MRI, regardless the disease duration. On the contrary normal thigh and leg muscle MRI or CT scans were observed in 4/15 (27%) patients, all mutated in SCN4A. Variable degrees of fatty changes were found in patients mutated in SCN4A, CACNA1S and CLCN1. No differences on overall score of fatty infiltration were detected between NDM and PP (p-value = 0.953) neither between presence or absence of permanent weakness (p value = 0.951). Our data confirm the presence of muscle fatty changes in the majority of SMC patients, although without any specific pattern of involvement. However muscle MRI may be a useful tool for longitudinal follow-up of SMC patients, in particular to evaluate the occurrence and the progression of fixed myopathy. PMID- 27199536 TI - Muscle MRI in muscular dystrophies. AB - Muscle MRI has become a very useful tool in the diagnosis and follow-up of patients with muscle dystrophies. Muscle MRI provides us about many aspects of the structure and function of skeletal muscles, such as the presence of oedema or fatty infiltration. In the last years many reports have described the particular muscles that are involved in these muscle disease. This knowledge can facilitate the diagnosis in many cases. In the present paper we review the main changes observed in muscle MRI of patients with muscle dystrophies. PMID- 27199539 TI - A multi-parametric protocol to study exercise intolerance in McArdle's disease. AB - McArdle's disease is the most common metabolic myopathy of muscle carbohydrate metabolism, due to deficiency of myophosphorylase and alteration of glycogen breakdown in muscle. The clinical manifestations usually begin in young adulthood, with exercise intolerance, exercise-induced muscle cramps, pain and recurrent episodes of myoglobinuria. Many patients experience the second wind phenomenon, characterized by an improved tolerance for aerobic exercise approximately after eight minutes of motor activity, secondary to the increased availability of blood glucose and free fatty acids associated to an enhanced glucose uptake by muscle cells. In this study, we aimed to test a multi parametric protocol in order to detect the impairment of muscular metabolism and motor performance in patients with McArdle's disease. We enrolled 5 patients and 5 age-matched healthy subjects, that were evaluated by: (01) monitoring of physical activity with an electronic armband; (02) testing of cardiopulmonary, metabolic and respiratory responses to exercise with a cardiopulmonary exercise test and analyzing muscle fatigue during exercise test by surface electromyography (04) evaluating blood lactate and oxidative stress biomarkers at rest and during exercise. The patients were tested at baseline and after three days of carbohydrate-rich diet integrated with tricarboxylic acid cycle intermediate and creatine. The multiparametric protocol proved to be useful to detect the oxidative capacity impairment and the second wind phenomenon of patients. We did not observe any significant differences of muscle metabolic response during the exercise test after three days of carbohydrate-rich diet. PMID- 27199538 TI - Novel mutations in LMNA A/C gene and associated phenotypes. AB - Mutations in the lamin A/C gene (LMNA) have been associated with several phenotypes ranging from systemic to prevalent of muscle, heart, skin, nerve etc. More recently they have been associated with dilated cardiomyopathy (DCM) and severe forms of arrhythmogenic right ventricular cardiomyopathy (ARVC). We report four novel mutations - 3 missense and 1 deletion - in 4 unrelated patients showing different phenotypes, ranging from the early onset congenital form of laminopathy to classical LGMD phenotype, to LGMD and heart involvement. All these newly identified variants were not found in 300 ethnicallymatched control subjects. The variant c.103-105del CTG was described post-mortem in a young patient with congenital muscular dystrophy who presented at the age of 9 a first degree A-V block and subsequently several episodes of supraventricular parossystic tachycardia. Two patients presented as onset symptom lower limbs muscle weakness, and developed heart conduction defects requiring pacemaker implantation at the age of 26 and 38 years, respectively. One of them who carried the mutation c.1339G>C died at the age of 40 by intractable heart failure; the second one carrying the mutation 265C>T died at the age of 30, for a trmboembolic event. A classical LGMD phenotype without heart involvement was observed in the patient with the mutation 1579C>T, who died at the age of 68 years for respiratory insufficiency. PMID- 27199540 TI - Multidimensional aspects of pain in myotonic dystrophies. AB - To analyze the frequency and intensity of pain and its association with different characteristics of patients with myotonic dystrophy type 1 (DM1) and type 2 (DM2), 52 adult genetically confirmed DM1 and 44 DM2 patients completed the Brief Pain Inventory questionnaire (BPI). Frequency and average intensity of pain on numerical rating scale (0-10) were similar in DM1 and DM2 (88% vs. 86% and 4.6 +/ 2.3 vs. 4.2 +/- 1.8, respectively, p > 0.05). In DM1, average pain intensity showed strong association with longer duration of disease and inverse relation with cognition. In DM2, average pain intensity showed association with female gender and emotions. Average pain intensity correlated with Individualized Neuromuscular Quality of Life (INQoL) total score in both DM1 (rho = +0.30, p < 0.05) and DM2 patients (rho = +0.61, p < 0.01). In conclusion, the majority of DM1 and DM2 patients have mild to moderate pain. Our results open new opportunities for behavioral and cognitive interventions. PMID- 27199541 TI - Muscle histology changes after short term vibration training in healthy controls. AB - In search for additional counter measures of muscle atrophy vibration exercise training may have substantial effort for patients with neuromuscular disorders. To cover safety aspects and obtain muscle morphology data, a pilot study was performed in eleven healthy men. Countermovement jump, squat jump, drop jump and one repetition maximum test (1RM) were performed on a force platform before and after a 6 week training period. No severe side effects were found. Repeated needle muscle biopsies of the vastus lateralis muscle revealed a selective pre- to post-training type-2 myofiber hypertrophy of up to 50 %. The hypertrophy factors were 160 and 310, for type-2 myofibers. The mechanography system showed a significant increase in the 1RM maximum weight lifted (pre: 111,8 kg +/- 11,5; post: 140,9 kg +/- 13,00; p < 0,001). Vibration exercise is a safe and effective technique which desires further approval as counter measure in different types of neuromuscular atrophy. PMID- 27199543 TI - Minutes of the European POmpe Consortium (EPOC) Meeting March 27 to 28, 2015, Munich, Germany. PMID- 27199542 TI - Rhabdomyolysis in hyponatremia and paraneoplastic syndrome of inappropriate antidiuresis. AB - We report a 26-year-old woman admitted to our hospital for generalized tonic seizure. Laboratory investigations revealed severe hyponatremia possibly triggered by vomiting and diarrhea. 24 hours after correction of hyponatremia she developed diffuse myalgias and marked hyperCKemia. Syndrome of inappropriate antidiuresis (SIAD) was suspected as cause of hyponatremia. Abnormal vaginal bleeding prompts gynecological evaluation and a small-cell carcinoma of uterine cervix was detected. PMID- 27199544 TI - Phylogenetic and Structural Analysis of Polyketide Synthases in Aspergilli. AB - Polyketide synthases (PKSs) of Aspergillus species are multidomain and multifunctional megaenzymes that play an important role in the synthesis of diverse polyketide compounds. Putative PKS protein sequences from Aspergillus species representing medically, agriculturally, and industrially important Aspergillus species were chosen and screened for in silico studies. Six candidate Aspergillus species, Aspergillus fumigatus Af293, Aspergillus flavus NRRL3357, Aspergillus niger CBS 513.88, Aspergillus terreus NIH2624, Aspergillus oryzae RIB40, and Aspergillus clavatus NRRL1, were selected to study the PKS phylogeny. Full-length PKS proteins and only ketosynthase (KS) domain sequence were retrieved for independent phylogenetic analysis from the aforementioned species, and phylogenetic analysis was performed with characterized fungal PKS. This resulted into grouping of Aspergilli PKSs into nonreducing (NR), partially reducing (PR), and highly reducing (HR) PKS enzymes. Eight distinct clades with unique domain arrangements were classified based on homology with functionally characterized PKS enzymes. Conserved motif signatures corresponding to each type of PKS were observed. Three proteins from Protein Data Bank corresponding to NR, PR, and HR type of PKS (XP_002384329.1, XP_753141.2, and XP_001402408.2, respectively) were selected for mapping of conserved motifs on three-dimensional structures of KS domain. Structural variations were found at the active sites on modeled NR, PR, and HR enzymes of Aspergillus. It was observed that the number of iteration cycles was dependent on the size of the cavity in the active site of the PKS enzyme correlating with a type with reducing or NR products, such as pigment, 6MSA, and lovastatin. The current study reports the grouping and classification of PKS proteins of Aspergilli for possible exploration of novel polyketides based on sequence homology; this information can be useful for selection of PKS for polyketide exploration and specific detection of Aspergilli. PMID- 27199546 TI - Selecting Reliable mRNA Expression Measurements Across Platforms Improves Downstream Analysis. AB - With increasing use of publicly available gene expression data sets, the quality of the expression data is a critical issue for downstream analysis, gene signature development, and cross-validation of data sets. Thus, identifying reliable expression measurements by leveraging multiple mRNA expression platforms is an important analytical task. In this study, we propose a statistical framework for selecting reliable measurements between platforms by modeling the correlations of mRNA expression levels using a beta-mixture model. The model based selection provides an effective and objective way to separate good probes from probes with low quality, thereby improving the efficiency and accuracy of the analysis. The proposed method can be used to compare two microarray technologies or microarray and RNA sequencing measurements. We tested the approach in two matched profiling data sets, using microarray gene expression measurements from the same samples profiled on both Affymetrix and Illumina platforms. We also applied the algorithm to mRNA expression data to compare Affymetrix microarray data with RNA sequencing measurements. The algorithm successfully identified probes/genes with reliable measurements. Removing the unreliable measurements resulted in significant improvements for gene signature development and functional annotations. PMID- 27199547 TI - Heme Oxygenase Activity Correlates with Serum Indices of Iron Homeostasis in Healthy Nonsmokers. AB - Heme oxygenase (HO) catalyzes the breakdown of heme to carbon monoxide, iron, and biliverdin. While the use of genetically altered animal models in investigation has established distinct associations between HO activity and systemic iron availability, studies have not yet confirmed such participation of HO in iron homeostasis of humans. Carbon monoxide produced through HO activity will bind to hemoglobin in circulating erythrocytes, and therefore, blood carboxyhemoglobin (COHb) can be used as an index of HO activity. Using the second National Health and Nutrition Examination Survey, we tested the postulate that HO activity correlates with serum indices of iron homeostasis in healthy nonsmokers. The investigation included 844 lifetime nonsmokers (586 females) 18 years of age and older in the study population. Significant correlations were demonstrated between COHb and several indices of iron homeostasis including serum levels of both ferritin and iron and percentage iron saturation of transferrin. There was no significant association between COHb and hemoglobin, the largest repository of heme in the human body, which functions as the substrate for HO. We conclude that HO activity contributes to human iron homeostasis with significant correlations between COHb and serum ferritin and iron levels and percentage iron saturation of transferrin. PMID- 27199548 TI - Fungistatic activity of all-trans retinoic acid against Aspergillus fumigatus and Candida albicans. AB - PURPOSE: Fungal infections are a major complication in hematologic and neoplastic patients causing severe morbidity and mortality. Aspergillus fumigatus and Candida albicans are among the most invasive opportunistic pathogens in immunocompromised patients, and classic antifungal drugs are frequently unsuccessful in these patients. Recent reports hypothesize that the antifungal efficacy of all-trans retinoic acid (ATRA) is mainly related to its strong capacity to stimulate monocyte-mediated immunity, but no consideration was given to its potential direct fungistatic activity. Moreover, ATRA offers the opportunity for systemic therapy. METHODS AND RESULTS: We investigated the efficacy of ATRA at different concentrations for its antifungal activity against opportunistic A. fumigatus and C. albicans obtained from clinical samples according to standard protocols. A fungistatic activity of ATRA on A. fumigatus and C. albicans at 0.5-1 mM concentration was documented up to 7 days. CONCLUSION: This is the first evidence of a direct and strong fungistatic activity of ATRA against A. fumigatus and C. albicans. The potential adjuvant therapeutic application of ATRA might be useful in the treatment and/or prevention of systemic mycoses in immunocompromised patients. The discovery of a direct fungistatic activity, in association with its reported immunomodulatory properties, makes ATRA an excellent candidate for new combined antifungal strategies for systemic mycoses in immunocompromised and cancer patients. PMID- 27199545 TI - Metagenomics, Metatranscriptomics, and Metabolomics Approaches for Microbiome Analysis. AB - Microbiomes are ubiquitous and are found in the ocean, the soil, and in/on other living organisms. Changes in the microbiome can impact the health of the environmental niche in which they reside. In order to learn more about these communities, different approaches based on data from multiple omics have been pursued. Metagenomics produces a taxonomical profile of the sample, metatranscriptomics helps us to obtain a functional profile, and metabolomics completes the picture by determining which byproducts are being released into the environment. Although each approach provides valuable information separately, we show that, when combined, they paint a more comprehensive picture. We conclude with a review of network-based approaches as applied to integrative studies, which we believe holds the key to in-depth understanding of microbiomes. PMID- 27199549 TI - Participants' perception of pharmaceutical clinical research: a cross-sectional controlled study. AB - BACKGROUND: There is scarce scientific information assessing participants' perception of pharmaceutical research in developed and developing countries concerning the risks, safety, and purpose of clinical trials. METHODS: To assess the perception that 604 trial participants (cases) and 604 nonparticipants (controls) of pharmaceutical clinical trials have about pharmaceutical clinical research, we surveyed participants with one of four chronic diseases from 12 research sites throughout Mexico. RESULTS: Participation in clinical trials positively influences the perception of pharmaceutical clinical research. More cases (65.4%) than controls (50.7%) perceived that the main purpose of pharmaceutical research is to cure more diseases and to do so more effectively. In addition, more cases considered that there are significant benefits when participating in a research study, such as excellent medical care and extra free services, with this being the most important motivation to participate for both groups (cases 52%, controls 54.5%). We also found a sense of trust in their physicians to deal with adverse events, and the perception that clinical research is a benefit to their health, rather than a risk. More controls believed that clinical trial participants' health is put at risk (57% vs 33.3%). More cases (99.2%) than controls (77.5%) would recommend participating in a clinical trial, and 90% of cases would enroll in a clinical trial again. CONCLUSION: Participation in clinical trials positively influences the perception that participants have about pharmaceutical clinical research when compared to nonparticipants. This information needs to be conveyed to clinicians, public health authorities, and general population to overcome misconceptions. PMID- 27199550 TI - Modeling of the Glycolysis Pathway in Plasmodium falciparum using Petri Nets. AB - Malaria is one of the deadly diseases, which affects a large number of the world's population. The Plasmodium falciparum parasite during erythrocyte stages produces its energy mainly through anaerobic glycolysis, with pyruvate being converted into lactate. The glycolysis metabolism in P. falci-parum is one of the important metabolic pathways of the parasite because the parasite is entirely dependent on it for energy. Also, several glycolytic enzymes have been proposed as drug targets. Petri nets (PNs) have been recognized as one of the important models for representing biological pathways. In this work, we built a qualitative PN model for the glycolysis pathway in P. falciparum and analyzed the model for its structural and quantitative properties using PN theory. From PlasmoCyc files, a total of 11 reactions were extracted; 6 of these were reversible and 5 were irreversible. These reactions were catalyzed by a total number of 13 enzymes. We extracted some of the essential reactions in the pathway using PN model, which are the possible drug targets without which the pathway cannot function. This model also helps to improve the understanding of the biological processes within this pathway. PMID- 27199551 TI - Current Developments in RNA Sequence Analysis. PMID- 27199552 TI - Machine Learning Data Imputation and Classification in a Multicohort Hypertension Clinical Study. AB - Health-care initiatives are pushing the development and utilization of clinical data for medical discovery and translational research studies. Machine learning tools implemented for Big Data have been applied to detect patterns in complex diseases. This study focuses on hypertension and examines phenotype data across a major clinical study called Minority Health Genomics and Translational Research Repository Database composed of self-reported African American (AA) participants combined with related cohorts. Prior genome-wide association studies for hypertension in AAs presumed that an increase of disease burden in susceptible populations is due to rare variants. But genomic analysis of hypertension, even those designed to focus on rare variants, has yielded marginal genome-wide results over many studies. Machine learning and other nonparametric statistical methods have recently been shown to uncover relationships in complex phenotypes, genotypes, and clinical data. We trained neural networks with phenotype data for missing-data imputation to increase the usable size of a clinical data set. Validity was established by showing performance effects using the expanded data set for the association of phenotype variables with case/control status of patients. Data mining classification tools were used to generate association rules. PMID- 27199553 TI - Do fall-risk-increasing drugs have an impact on mortality in older hip fracture patients? A population-based cohort study. AB - OBJECTIVE: The aim of this study was to assess the mortality in hip fracture patients with regard to use of fall-risk-increasing drugs (FRIDs), by comparing survival in exposed and nonexposed individuals. DESIGN: This was a general population-based cohort study. SETTINGS: Data on hip fracture patients were retrieved from three national databases. PARTICIPANTS: All hip fracture patients aged 60 years or older in a Swedish county in 2006 participated in this study. MEASUREMENTS: We studied the mortality in hip fracture patients by comparing those exposed to FRIDs, combinations of FRIDs, and polypharmacy to nonexposed patients, adjusting for age and sex. For survival estimates in patients using four or more FRIDs, a Cox regression analysis was used, adjusting for age, sex, and use of any four or more drugs. RESULTS: First-year all-cause mortality was 24.6% (N=503) in 2,043 hip fracture patients aged 60 years or older, including 170 males (33.8%) and 333 females (66.2%). Patients prescribed four or more FRIDs, five or more drugs (polypharmacy), psychotropic drugs, and cardiovascular drugs showed significantly increased first-year mortality. Exposure to four or more FRIDs (518 patients, 25.4%) was associated with an increased mortality at 30 days with odds ratios (ORs) 2.01 (95% confidence interval [CI] 1.44-2.79), 90 days with OR 1.56 (95% CI 1.19-2.04), 180 days with OR 1.54 (95% CI 1.20-1.97), and 365 days with OR 1.43 (95% CI 1.13-1.80). Cox regression analyses adjusted for age, sex, and use of any four or more drugs showed a significantly higher mortality in patients treated with four or more FRIDs at 90 days (P=0.015) and 180 days (P=0.012) compared to patients treated with three or less FRIDs. CONCLUSION: First-year all-cause mortality was significantly higher in older hip fracture patients exposed before the fracture to FRIDs, in particular to four or more FRIDs, polypharmacy, psychotropic, and cardiovascular drugs. Interventions aiming to optimize both safety and benefit of drug treatment for older people should include limiting the use of FRIDs. PMID- 27199554 TI - In vitro modeling of COPD inflammation and limitation of p38 inhibitor - SB203580. AB - BACKGROUND: Systemic inflammation and steroid resistance are the hallmarks of COPD. We examined the impact of p38 inhibitor (SB203580) in in vitro assays of systemic inflammation using pulmonary cells and patients' sera. OBJECTIVE AND METHODS: Data from 66 COPD patients and 15 age-/sex-matched healthy controls were compared. Interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-alpha), and CCL5 were measured in serum samples and culture media from peripheral blood mononuclear cells. The impact of sera on IL-10 and CCL5 expression in alveolar macrophage cell line (MH-S) was examined. The in vitro effects of SB203580 on lipopolysaccharide-induced inflammation were investigated. RESULTS: Peripheral blood mononuclear cells from Global initiative for chronic Obstructive Lung Disease (GOLD) D patients produced more CCL5 and TNF-alpha, and less IL-10 compared to GOLD A-C patients. SB203580 treatment suppressed CCL5 and TNF-alpha and stimulated IL-10 production; however, the effect of SB203580 on IL-10 was lower in the COPD group. Culture of MH-S cells with COPD serum showed a significant increase in CCL5 and a significant decrease in IL-10 compared to healthy serum. This effect was not suppressed with SB203580 treatment. CONCLUSION: COPD serum has a potent proinflammatory effect on pulmonary cells. Inhibition of p38 phoshorylation had a limited effect in restoring impaired lymphocyte function and suppressing inflammation induced by COPD serum, implying important p38-independent inflammatory mechanisms in COPD. PMID- 27199555 TI - Chronic obstructive pulmonary disease phenotypes and balance impairment. AB - BACKGROUND/OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a respiratory disease that results in airflow limitation and respiratory distress, also having many nonrespiratory manifestations that affect both function and mobility. Preliminary evidence suggests that balance deficits constitute an important secondary impairment in individuals with COPD. Our objective was to investigate balance performance in two groups of COPD patients with different body compositions and to observe which of these groups are more likely to experience falls in the future. METHODS: We included 27 stable COPD patients and 17 healthy individuals who performed a series of balance tests. The COPD patients were divided in two groups: emphysematous and bronchitic. Patients completed the activities balance confidence scale and the COPD assessment test questionnaire and afterward performed the Berg Balance Scale, timed up and go, single leg stance and 6-minute walking distance test. We analyzed the differences in the balance tests between the studied groups. RESULTS: Bronchitic COPD was associated with a decreased value when compared to emphysematous COPD for the following variables: single leg stance (8.7 vs 15.6; P<0.001) and activities balance confidence (53.2 vs 74.2; P=0.001). Bronchitic COPD patients had a significantly higher value of timed up and go test compared to patients with emphysematous COPD (14.7 vs 12.8; P=0.001). CONCLUSION: Patients with COPD have a higher balance impairment than their healthy peers. Moreover, we observed that the bronchitic COPD phenotype is more likely to experience falls compared to the emphysematous phenotype. PMID- 27199556 TI - Manganese dioxide nanosheets-based redox/pH-responsive drug delivery system for cancer theranostic application. AB - The aim of this study was to construct redox- and pH-responsive degradable manganese dioxide (MnO2) nanosheets for cancer theranostic application. The small MnO2 nanosheets were synthesized, and then functionalized by hyaluronic acid (HA), demonstrating excellent stability and tumor-targeting ability. Cisplatin (cis-diamminedichloroplatinum [CDDP]) was absorbed by the nanosheets through a physical action, which was designed as MnO2/HA/CDDP. The prepared MnO2/HA/CDDP formulation was able to efficiently deliver CDDP to tumor cells in vitro and in vivo, resulting in improved therapeutic efficiency. Subsequently, they were triggered by lower pH and higher level of reduced glutathione to generate Mn(2+), enabling magnetic resonance imaging. The smart multifunctional system combining efficient magnetic resonance imaging and chemotherapy has the potential to be used as a tumor-targeting theranostic nanomedicine. PMID- 27199557 TI - Facile synthesis of soybean phospholipid-encapsulated MoS2 nanosheets for efficient in vitro and in vivo photothermal regression of breast tumor. AB - Two-dimensional MoS2 nanosheet has been extensively explored as a photothermal agent for tumor regression; however, its surface modification remains a great challenge. Herein, as an alternative to surface polyethylene glycol modification (PEGylation), a facile approach based on "thin-film" strategy has been proposed for the first time to produce soybean phospholipid-encapsulated MoS2 (SP-MoS2) nanosheets. By simply vacuum-treating MoS2 nanosheets/soybean phospholipid/chloroform dispersion in a rotary evaporator, SP-MoS2 nanosheet was successfully constructed. Owing to the steric hindrance of polymer chains, the surface-coated soybean phospholipid endowed MoS2 nanosheets with excellent colloidal stability. Without showing detectable in vitro and in vivo hemolysis, coagulation, and cyto-/histotoxicity, the constructed SP-MoS2 nanosheets showed good photothermal conversion performance and photothermal stability. SP-MoS2 nanosheet was shown to be a promising platform for in vitro and in vivo breast tumor photothermal therapy. The produced SP-MoS2 nanosheets featured low cost, simple fabrication, and good in vivo hemo-/histocompatibility and hold promising potential for future clinical tumor therapy. PMID- 27199559 TI - Investigation of facial emotion recognition, alexithymia, and levels of anxiety and depression in patients with somatic symptoms and related disorders. AB - BACKGROUND: The concept of facial emotion recognition is well established in various neuropsychiatric disorders. Although emotional disturbances are strongly associated with somatoform disorders, there are a restricted number of studies that have investigated facial emotion recognition in somatoform disorders. Furthermore, there have been no studies that have regarded this issue using the new diagnostic criteria for somatoform disorders as somatic symptoms and related disorders (SSD). In this study, we aimed to compare the factors of facial emotion recognition between patients with SSD and age- and sex-matched healthy controls (HC) and to retest and investigate the factors of facial emotion recognition using the new criteria for SSD. PATIENTS AND METHODS: After applying the inclusion and exclusion criteria, 54 patients who were diagnosed with SSD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria and 46 age- and sex-matched HC were selected to participate in the present study. Facial emotion recognition, alexithymia, and the status of anxiety and depression were compared between the groups. RESULTS: Patients with SSD had significantly decreased scores of facial emotion for fear faces, disgust faces, and neutral faces compared with age- and sex-matched HC (t= 2.88, P=0.005; t=-2.86, P=0.005; and t=-2.56, P=0.009, respectively). After eliminating the effects of alexithymia and depressive and anxious states, the groups were found to be similar in terms of their responses to facial emotion and mean reaction time to facial emotions. DISCUSSION: Although there have been limited numbers of studies that have examined the recognition of facial emotion in patients with somatoform disorders, our study is the first to investigate facial recognition in patients with SSD diagnosed according to the DSM-5 criteria. Recognition of facial emotion was found to be disturbed in patients with SSD. However, our findings suggest that disturbances in facial recognition were significantly associated with alexithymia and the status of depression and anxiety, which is consistent with the previous studies. Further studies are needed to highlight the associations between facial emotion recognition and SSD. PMID- 27199558 TI - Phytosynthesis of silver nanoparticles using Artemisia marschalliana Sprengel aerial part extract and assessment of their antioxidant, anticancer, and antibacterial properties. AB - A rapid phytosynthesis of silver nanoparticles (AgNPs) using an extract from the aerial parts of Artemisia marschalliana Sprengel was investigated in this study. The synthesized AgNPs using A. marschalliana extract was analyzed by UV-visible spectroscopy, X-ray diffraction, and Fourier transform infrared spectroscopy and further characterized by transmission electron microscopy, scanning electron microscopy, zeta potential, and energy-dispersive spectroscopy. Characteristic absorption bands of AgNPs were found near 430 nm in the UV-vis spectrum. Energy dispersive spectroscopy analysis of AgNPs in the energy range 2-4 keV confirmed the silver signal due to surface plasmon resonance. Scanning electron microscopy and transmission electron microscopy results revealed that the AgNPs were mostly spherical with an average size ranging from 5 nm to 50 nm. The zeta potential value of -31 mV confirmed the stability of the AgNPs. AgNPs produced using the aqueous A. marschalliana extract might serve as a potent in vitro antioxidant, as revealed by 2,2-diphenyl-1-picryl hydrazyl assay. The present study demonstrates the anticancer properties of phytosynthesized AgNPs against human gastric carcinoma AGS cells. AgNPs exerted a dose-dependent inhibitory effect on the viability of cells. Real-time polymerase chain reaction was used for the investigation of Bax and Bcl-2 gene expression in cancer and normal cell lines. Our findings show that the mRNA levels of pro-apoptotic Bax gene expression were significantly upregulated, while the expression of anti-apoptotic Bcl-2 was declined in cells treated with AgNPs compared to normal cells. In addition, flow cytometric analysis showed that the number of early and late apoptotic AGS cells was significantly enhanced following treatment with AgNPs as compared to untreated cells. In addition, the AgNPs showed strong antibacterial properties against tested pathogenic bacteria such as Staphylococcus aureus, Bacillus cereus, Acinetobacter baumannii, and Pseudomonas aeruginosa. Based on the obtained data, we suggest that phytosynthesized AgNPs are good alternatives in the treatment of diseases because of the presence of bioactive agents. PMID- 27199561 TI - Becoming FASD Informed: Strengthening Practice and Programs Working with Women with FASD. AB - There is growing appreciation among health and social care providers, especially those working in community-based programs with women or young people with substance use problems and/or who have experienced violence, maltreatment, or trauma, that a high number of their program participants may have been prenatally exposed to alcohol or have fetal alcohol spectrum disorder (FASD). This article provides a conceptualization of the key components of an FASD-informed approach. Drawing on the emerging literature and the author's research identifying the support needs and promising approaches in working with women, young adults, and adults with FASD, as well as evaluations of FASD-related programs, the article discusses what an FASD-informed approach is, why it is centrally important in working with women, adults, and young people who may have FASD, underlying principles of an FASD-informed approach, and examples of FASD-informed adaptations to practice, programming, and the physical environment. In this discussion, the benefits of using an FASD-informed approach for service providers and women living with FASD and their families, as well as conceptualization of FASD-informed policy and systems are highlighted. PMID- 27199560 TI - Prevention of Fetal Alcohol Spectrum Disorder: Current Canadian Efforts and Analysis of Gaps. AB - Effective prevention of risky alcohol use in pregnancy involves much more than providing information about the risk of potential birth defects and developmental disabilities in children. To categorize the breadth of possible initiatives, Canadian experts have identified a four-part framework for fetal alcohol spectrum disorder (FASD) prevention: Level 1, public awareness and broad health promotion; Level 2, conversations about alcohol with women of childbearing age and their partners; Level 3, specialized support for pregnant women; and Level 4, postpartum support for new mothers. In order to describe the level of services across Canada, 50 Canadian service providers, civil servants, and researchers working in the area of FASD prevention were involved in an online Delphi survey process to create a snapshot of current FASD prevention efforts, identify gaps, and provide ideas on how to close these gaps to improve FASD prevention. Promising Canadian practices and key areas for future action are described. Overall, Canadian FASD prevention programming reflects evidence-based practices; however, there are many opportunities to improve scope and availability of these initiatives. PMID- 27199562 TI - Blogging to Quit Smoking: Sharing Stories from Women of Childbearing Years in Ontario. AB - This study examined the degree to which the pregnant or postpartum women, in the process of quitting smoking, felt that writing in a blog about their smoking cessation journeys helped them in their efforts to become or remain smoke free. Five women who blogged for Prevention of Gestational and Neonatal Exposure to Tobacco Smoke (a website designed to help pregnant and postpartum women quit smoking) were interviewed about their experiences as bloggers. Participants were asked to complete an online survey, which had closed-ended questions regarding their sociodemographic and smoking characteristics. Once they completed the survey, semistructured qualitative interviews were conducted over the phone. Findings suggest that blogging might combine several evidence-based behavioral strategies for tobacco cessation, such as journaling and getting support from others who use tobacco. Being part of a blogging community of women who have experienced or are experiencing similar challenges can be therapeutic and help women gain confidence in their ability to quit smoking. In conclusion, blogging may help pregnant and postpartum women quit smoking by increasing their social support and promoting self-reflection. PMID- 27199564 TI - Harm to Others From Substance Use and Abuse. PMID- 27199563 TI - Improving Access to Long-Acting Contraceptive Methods and Reducing Unplanned Pregnancy Among Women with Substance Use Disorders. AB - Much has been written about the consequences of substance use in pregnancy, but there has been far less focus on the prevention of unintended pregnancies in women with substance use disorders (SUDs). We examine the literature on pregnancy incidence for women with SUDs, the clinical and economic benefits of increasing access to long-acting reversible contraceptive (LARC) methods in this population, and the current hurdles to increased access and uptake. High rates of unintended pregnancies and poor physical and psychosocial outcomes among women with SUDs underscore the need for increased access to, and uptake of, LARC methods among these women. A small number of studies that focused on improving access to contraception, especially LARC, via integrated contraception services predominantly provided in drug treatment programs were identified. However, a number of barriers remain, highlighting that much more research is needed in this area. PMID- 27199565 TI - Elevated Atmospheric Levels of Benzene and Benzene-Related Compounds from Unconventional Shale Extraction and Processing: Human Health Concern for Residential Communities. AB - BACKGROUND: The advancement of natural gas (NG) extraction across the United States (U.S.) raises concern for potential exposure to hazardous air pollutants (HAPs). Benzene, a HAP and a primary chemical of concern due to its classification as a known human carcinogen, is present in petroleum-rich geologic formations and is formed during the combustion of bypass NG. It is a component in solvents, paraffin breakers, and fuels used in NG extraction and processing (E&P). OBJECTIVES: The objectives of this study are to confirm the presence of benzene and benzene-related compounds (benzene[s]) in residential areas, where unconventional shale E&P is occurring, and to determine if benzene[s] exists in elevated atmospheric concentrations when compared to national background levels. METHODS: Ambient air sampling was conducted in six counties in the Dallas/Fort Worth Metroplex with passive samples collected in evacuated 6-L Summa canisters. Samples were analyzed by gas chromatography/mass spectrometry, with sampling performed at variable distances from the facility fence line. RESULTS: Elevated concentrations of benzene[s] in the atmosphere were identified when compared to U.S. Environmental Protection Agency's Urban Air Toxics Monitoring Program. The 24-hour benzene concentrations ranged from 0.6 parts per billion by volume (ppbv) to 592 ppbv, with 1-hour concentrations from 2.94 ppbv to 2,900.20 ppbv. CONCLUSION: Benzene is a known human carcinogen capable of multisystem health effects. Exposure to benzene is correlated with bone marrow and blood-forming organ damage and immune system depression. Sensitive populations (children, pregnant women, elderly, immunocompromised) and occupational workers are at increased risk for adverse health effects from elevated atmospheric levels of benzene[s] in residential areas with unconventional shale E&P. PMID- 27199567 TI - Stathmin1 increases radioresistance by enhancing autophagy in non-small-cell lung cancer cells. AB - Radioresistance has been demonstrated to be involved in the poor prognosis of patients with non-small-cell lung cancer (NSCLC). However, the underlying mechanism remains largely unclear. Investigation on special therapeutic targets associated with radioresistance shows promises for the enhancement of clinical radiotherapy effect toward NSCLC. This study aimed to reveal the role of Stathmin1 (STMN1) in radioresistance in NSCLC as well as the underlying mechanism. Our data showed that the protein levels of STMN1 were significantly upregulated in NSCLC cells subjected to radiation, accompanied with the activation of autophagy. Knockdown of STMN1 expression enhanced the sensitivity of NSCLC cells to X-ray, and the radiation-induced autophagy was also inhibited. Molecular mechanism investigation showed that knockdown of STMN1 expression upregulated the activity of phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway in NSCLC cells. Moreover, the activation of PI3K/mTOR signaling showed an inhibitory effect on the autophagy and radioresistance induced by STMN1 in NSCLC cells. In addition, luciferase reporter assay data indicated that STMN1 was a direct target gene of miR-101, which had been reported to be an inhibitor of autophagy. Based on these data, we suggest that as a target gene of miR-101, STMN1 promotes the radioresistance by induction of autophagy through PI3K/mTOR signaling pathway in NSCLC. Therefore, STMN1 may become a potential therapeutic target for NSCLC radiotherapy. PMID- 27199566 TI - Diet Versus Exercise in Weight Loss and Maintenance: Focus on Tryptophan. AB - An association between mood disturbance, the inability to lose or to stop gaining weight, and a craving for carbohydrates is manifested by many people who are overweight or are becoming so. In a recent study, we observed that low-calorie weight loss diet lowered not only levels of leptin but also levels of essential amino acid tryptophan (TRP) significantly. The disturbed metabolism of TRP might affect biosynthesis of serotonin and could thereby increase the susceptibility for mood disturbances and carbohydrate craving, increasing the cessation probability of weight reduction programs. Alternatively, moderate physical exercise - a potent stimulus to modulate (reduce/normalize) proinflammatory cytokines, which may affect TRP levels - could be helpful in improving mood status and preventing uncontrolled weight gain. In contrast, excessive physical exercise may induce breakdown of TRP when proinflammatory cascades together with TRP-degrading enzyme indoleamine 2,3-dioxygenase-1 are stimulated, which may lead to neuropsychiatric symptoms such as fatigue and low mood. PMID- 27199568 TI - Hospitalization and cost after switching from atypical to typical antipsychotics in schizophrenia patients in Thailand. AB - BACKGROUND: Several clinical practice guidelines suggest using atypical over typical antipsychotics in patients diagnosed with schizophrenia. Nevertheless, cost-containment policy urged restricting usage of atypical antipsychotics and switching from atypical to typical antipsychotics. OBJECTIVE: This study aimed to evaluate clinical and economic impacts of switching from atypical to typical antipsychotics in schizophrenia patients in Thailand. METHODS: From October 2010 through September 2013, a retrospective cohort study was performed utilizing electronic database of two tertiary hospitals. Schizophrenia patients aged 18 years or older and being treated with atypical antipsychotics were included. Patients were classified as atypical antipsychotic switching group if they switched to typical antipsychotics after 180 days of continual atypical antipsychotics therapy. Outcomes were schizophrenia-related hospitalization and total health care cost. Logistic and Poisson regression were used to evaluate the risk of hospitalization, and generalized linear model with gamma distribution was used to determine the health care cost. All analyses were adjusted by employing propensity score and multivariable analyses. All cost estimates were adjusted according to 2013 consumer price index and converted to US$ at an exchange rate of 32.85 Thai bahts/US$. RESULTS: A total of 2,354 patients were included. Of them, 166 (7.1%) patients switched to typical antipsychotics. The adjusted odds ratio for schizophrenia-related hospitalization in atypical antipsychotic switching group was 1.87 (95% confidence interval [CI] 1.23-2.83). The adjusted incidence rate ratio was 2.44 (95% CI 1.57-3.79) for schizophrenia-related hospitalizations. The average total health care cost was lower in patients with antipsychotic switching (-$64; 95% CI -$459 to $332). CONCLUSION: Switching from atypical to typical antipsychotics is associated with an increased risk of schizophrenia-related hospitalization. Nonetheless, association with average total health care cost was not observed. These findings can be of use as a part of evidence in executing prospective cost-containment policy. PMID- 27199569 TI - Acute-onset rhabdomyolysis secondary to sitagliptin and atorvastatin interaction. AB - Rhabdomyolysis is a serious medical condition in which the skeletal muscle tissue gets damaged and breaks down at rapid rates, potentially leading to death if not managed early on. Rhabdomyolysis in adults has several etiologies such as crush injuries, prolonged immobilization, strenuous exercise, hormonal or metabolic causes, infections, and drug-drug interactions. We present a case report of the interaction of two drugs that are used commonly in the general population. We here discuss a case of a 60-year-old female who presented to the hospital with complaints of generalized weakness, muscle aches, and atypical chest pain for a week after her primary care physician started her on sitagliptin while she was already on atorvastatin. After review of literature, this is the second known case of such an interaction causing acute breakdown of skeletal musculature. PMID- 27199572 TI - Profound vascular stasis of retina and optic nerve following retrobulbar anesthesia. AB - INTRODUCTION: We aim to describe a mechanism of vision loss following vitrectomy surgery with retrobulbar block (RBB) associated with severe vascular stasis of the optic nerve and macula in order to improve safety of local anesthesia for ophthalmic surgery. CASE PRESENTATION: We report three cases of patients who underwent pars plana vitrectomy (PPV) with retrobulbar anesthesia with no retrobulbar hemorrhage or elevated intraocular pressure (IOP). At the beginning, in each case, hypoperfusion of optic nerve and macula was noted. In the case of one patient with significant vasculopathic risk factors, the vascular stasis was severe, while in the other two cases, it was mild-to-moderate. In all cases, the perfusion of posterior pole began to improve almost immediately following the start of PPV. Because the IOP was not elevated and no retrobulbar hemorrhage was present, this suggested a compartment syndrome in the intraconal space. The patient with severe vascular stasis developed finger-counting vision but had normal postoperative angiogram findings and unrevealing cardiovascular workup. In the other two milder cases, the occurrence of ischemia was not visually significant. CONCLUSION: Intraoperative ischemia should be considered in all cases of unexplained vision loss after ophthalmic surgery using RBB. Attention to vasculopathic risk factors and intra-operative hemodynamic parameters, in addition to the use of parabulbar block, may avoid this complication and permanent vision loss. PMID- 27199573 TI - A growth spurt in pediatric sleep research. PMID- 27199571 TI - Fibroblast growth factors 1 and 2 in cerebrospinal fluid are associated with HIV disease, methamphetamine use, and neurocognitive functioning. AB - BACKGROUND: Human immunodeficiency virus (HIV) and methamphetamine use commonly affect neurocognitive (NC) functioning. We evaluated the relationships between NC functioning and two fibroblast growth factors (FGFs) in volunteers who differed in HIV serostatus and methamphetamine dependence (MAD). METHODS: A total of 100 volunteers were categorized into four groups based on HIV serostatus and MAD in the prior year. FGF-1 and FGF-2 were measured in cerebrospinal fluid by enzyme linked immunosorbent assays along with two reference biomarkers (monocyte chemotactic protein [MCP]-1 and neopterin). Comprehensive NC testing was summarized by global and domain impairment ratings. RESULTS: Sixty-three volunteers were HIV+ and 59 had a history of MAD. FGF-1, FGF-2, and both reference biomarkers differed by HIV and MAD status. For example, FGF-1 levels were lower in subjects who had either HIV or MAD than in HIV- and MAD- controls (P=0.003). Multivariable regression identified that global NC impairment was associated with an interaction between FGF-1 and FGF-2 (model R(2)=0.09, P=0.01): higher FGF-2 levels were only associated with neurocognitive impairment among subjects who had lower FGF-1 levels. Including other covariates in the model (including antidepressant use) strengthened the model (model R(2)=0.18, P=0.004) but did not weaken the association with FGF-1 and FGF-2. Lower FGF-1 levels were associated with impairment in five of seven cognitive domains, more than FGF-2, MCP-1, or neopterin. CONCLUSION: These findings provide in vivo support that HIV and MAD alter expression of FGFs, which may contribute to the NC abnormalities associated with these conditions. These cross-sectional findings cannot establish causality and the therapeutic benefits of recombinant FGF-1 need to be investigated. PMID- 27199570 TI - The Extracellular-Regulated Kinase Effector Lk6 is Required for Glutamate Receptor Localization at the Drosophila Neuromuscular Junction. AB - The proper localization and synthesis of postsynaptic glutamate receptors are essential for synaptic plasticity. Synaptic translation initiation is thought to occur via the target of rapamycin (TOR) and mitogen-activated protein kinase signal-integrating kinase (Mnk) signaling pathways, which is downstream of extracellular-regulated kinase (ERK). We used the model glutamatergic synapse, the Drosophila neuromuscular junction, to better understand the roles of the Mnk and TOR signaling pathways in synapse development. These synapses contain non NMDA receptors that are most similar to AMPA receptors. Our data show that Lk6, the Drosophila homolog of Mnk1 and Mnk2, is required in either presynaptic neurons or postsynaptic muscle for the proper localization of the GluRIIA glutamate receptor subunit. Lk6 may signal through eukaryotic initiation factor (eIF) 4E to regulate the synaptic levels of GluRIIA as either interfering with eIF4E binding to eIF4G or expression of a nonphosphorylatable isoform of eIF4E resulted in a significant reduction in GluRIIA at the synapse. We also find that Lk6 and TOR may independently regulate synaptic levels of GluRIIA. PMID- 27199574 TI - Corneal Cross-Linking (with a Partial Deepithelization) in Keratoconus with Five Years of Follow-Up. AB - We performed a retrospective interventional case series including 80 eyes of 48 patients with keratoconus (KC) who were treated with modified corneal cross linking (CXL) for KC (with a partial deepithelization in a pattern of stripes). The average follow-up was 5.8 years (with a minimum of 5 years). At the last follow-up visit, compared with preoperative values, there were no significant changes in spherical equivalent, average keratometry, corneal thickness, corneal hysteresis, or corneal resistance factor. The distance-corrected visual acuity was 20/39 preoperatively and 20/36 postoperatively (P = 0.3). The endothelial cell count decreased by 4.7% (P < 0.005). These findings suggest that this modified corneal CXL technique is a safe and effective alternative to halt the progression of KC up to five years after the procedure. However, some concerns remain as to whether this technique can affect in some degree the corneal endothelial cells. PMID- 27199575 TI - Identification of High-Risk Patients with Non-ST Segment Elevation Myocardial Infarction using Strain Doppler Echocardiography: Correlation with Cardiac Magnetic Resonance Imaging. AB - Assessment of left ventricular (LV) function is important for decision-making and risk stratification in patients with acute coronary syndrome. Many patients with non-ST segment elevation myocardial infarction (NSTEMI) have substantial infarction, but these patients often do not reveal clinical signs of instability, and they rarely fulfill criteria for acute revascularization therapy. AIM: This study evaluated the potential of strain Doppler echocardiography analysis for the assessment of LV infarct size when compared with standard two-dimensional echo and cardiac magnetic resonance (CMR) data. METHODS: Thirty patients with NSTEMI were examined using echocardiography after hospitalization for 1.8 +/- 1.1 days for the assessment of left ventricular ejection fraction, wall motion score index (WMSI), and LV global longitudinal strain (GLS). Infarct size was assessed using delayed enhancement CMR 6.97 +/- 3.2 days after admission as a percentage of total myocardial volume. RESULTS: GLS was performed in 30 patients, and 82.9% of the LV segments were accepted for GLS analysis. Comparisons between patients with a complete set of GLS and standard echo, GLS and CMR were performed. The linear relationship demonstrated moderately strong and significant associations between GLS and ejection fraction (EF) as determined using standard echo (r = 0.452, P = 0.012), WMSI (r = 0.462, P = 0.010), and the gold standard CMR-determined EF (r = 0.57, P < 0.001). Receiver operating characteristic curves were used to analyze the ability of GLS to evaluate infarct size. GLS was the best predictor of infarct size in a multivariate linear regression analysis (beta = 1.51, P = 0.027). WMSI >1.125 and a GLS cutoff value of -11.29% identified patients with substantial infarction (>=12% of total myocardial volume measured using CMR) with accuracies of 76.7% and 80%, respectively. However, GLS remained the only independent predictor in a multivariate logistic regression analysis to identify an infarct size >=12%. CONCLUSION: GLS is a good predictor of infarct size in NSTEMI, and it may serve as a tool in conjunction with risk stratification scores for the selection of high-risk NSTEMI patients. PMID- 27199576 TI - Assessing the Value of BMI and Aerobic Capacity as Surrogate Markers for the Severity of Left Ventricular Diastolic Dysfunction in Patients with Type 2 Diabetes Who Are Obese. AB - Left ventricular diastolic dysfunction (LVDD) is one of the earliest signs for abnormal cardiac function in patients with type 2 diabetes (T2DM). It is important to explore the risk factors that will assist in identifying the severity of the LVDD in this population. We examined the influences of fitness and fatness on the level of left ventricular (LV) impairment in patients with T2DM. Twenty-five patients (age: 64.0 +/- 2.5 years, body mass index [BMI] = 36.0 +/- 1.5 kg/m(2), mean +/- standard error of measurement) with T2DM and preserved systolic function, but impaired diastolic function, mitral valve (MV) E/e', participated in the study. LV function was assessed using a stress echocardiograph, aerobic power was assessed with a sign- and symptom-limited graded exercise test, and the fatness level was assessed using Dual-energy X-ray absorptiometry and BMI. Patients in the higher 50% of BMI had higher lateral and septal MV E/e' (~34% and ~25%, respectively, both P < 0.001), compared to those in the lower 50% of BMI, with no difference in LV ejection fraction (LVEF) (P > 0.05). In addition, a higher BMI correlated with a higher lateral (r = 0.62, P < 0.001) and septal (r = 0.56, P < 0.01) E/e'. There was no such relationship for VO2peak. BMI and VO2peak were not correlated with LV systolic function (ejection fraction). In individuals with T2DM and diastolic dysfunction, a higher BMI was associated with worsening diastolic function independent of their aerobic capacity. The data provide a simple and practical approach for clinicians to assist in the early identification and diagnostics of functional changes in the heart diastolic function in this population. PMID- 27199577 TI - Resectable Cholangiocarcinoma: Reviewing the Role of Adjuvant Strategies. AB - Cholangiocarcinoma is a very heterogeneous and rare group of neoplasms originating from the perihilar, intra-, or extrahepatic bile duct epithelium. It represents only 3% of gastrointestinal cancers, although their incidence is increasing as its mortality increases. Surgical resection is the only potentially curative option, but unfortunately the resectability rate is low. Overall, these malignancies have got a very poor prognosis with a five-year survival rate of 5 10%. Although the five-year survival rate increases to 25-30% in the cases amenable to surgery, only 10-40% of patients present with resectable disease. Therefore, it is necessary to optimize the benefit of adjuvant strategies after surgery to increase the rate of curability. This study reviewed the role of adjuvant chemotherapy in resectable bile duct cancers. PMID- 27199578 TI - Correlation of Apgar Score with Asphyxial Hepatic Injury and Mortality in Newborns: A Prospective Observational Study From India. AB - OBJECTIVE: The objective of this study is to determine the correlation of Apgar score with asphyxial hepatic injury and neonatal mortality in moderately and severely asphyxiated newborns. MATERIAL AND METHODS: This is a secondary analysis of our prospective observational case-controlled study. Sixteen neonates with severe birth asphyxia (five-minute Apgar <=3) were compared with either 54 moderate asphyxia neonates (five-minute Apgar >3) or 30 normal neonates. Liver function tests were measured on postnatal days 1, 3, and 10 in the study and control groups. Neonatal mortality was observed in the study and control population. RESULTS: Correlation of Apgar score in severely asphyxiated neonates compared with normal Apgar score neonates and moderately asphyxiated neonates for deranged hepatic function showed significant correlation (odds ratio [OR] 4.88, 95% CI 3.26-5.84, P = 0.01 and OR 2.46, 95% CI 1.94-3.32, P = 0.02, respectively). There was a significant increase in serum lactate dehydrogenase (LDH) and total bilirubin on day 1 and serum LDH at age of 10th postnatal life in severely asphyxiated neonates when compared to moderately asphyxiated neonates, whereas there was a significant decrease in total bilirubin and serum albumin on day 3 in severely asphyxiated neonates. There was a significant increase in serum alanine transaminase, serum LDH, and total bilirubin on day 1, serum aspartate transaminase, serum LDH, and total bilirubin on day 3, and International Normalized Ratio on day 10 of postnatal life when severely asphyxiated neonates were compared with normal neonates. There was a significant reduction in total protein and serum albumin on day 1 and direct bilirubin on day 3 in severely asphyxiated neonates when compared with normal neonates. There was a significant increase in neonatal mortality in severely asphyxiated neonates when compared to the other two groups. Correlation of Apgar score in severely asphyxiated neonates compared with normal Apgar score neonates and moderately asphyxiated neonates for neonatal mortality showed significant correlation (odds ratio [OR] 2.23, 95% CI 1.42-3.04, P = 0.03 and OR 1.87, 95% CI 1.64-2.02, P = 0.04, respectively). CONCLUSION: The severity of hepatic dysfunction correlates well with increasing severity of asphyxia. The neonatal mortality also showed good correlation with Apgar score in our study, although we need a large multicentric trial to confirm our observations. Apgar score combined with hepatic dysfunction can be used as a prognostication marker for neonatal mortality. PMID- 27199579 TI - Accurate Point-of-Care Detection of Ruptured Fetal Membranes: Improved Diagnostic Performance Characteristics with a Monoclonal/Polyclonal Immunoassay. AB - OBJECTIVE: Accurate and timely diagnosis of rupture of membranes (ROM) is imperative to allow for gestational age-specific interventions. This study compared the diagnostic performance characteristics between two methods used for the detection of ROM as measured in the same patient. METHODS: Vaginal secretions were evaluated using the conventional fern test as well as a point-of-care monoclonal/polyclonal immunoassay test (ROM Plus((r))) in 75 pregnant patients who presented to labor and delivery with complaints of leaking amniotic fluid. Both tests were compared to analytical confirmation of ROM using three external laboratory tests. Diagnostic performance characteristics were calculated including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy. RESULTS: Diagnostic performance characteristics uniformly favored ROM detection using the immunoassay test compared to the fern test: sensitivity (100% vs. 77.8%), specificity (94.8% vs. 79.3%), PPV (75% vs. 36.8%), NPV (100% vs. 95.8%), and accuracy (95.5% vs. 79.1%). CONCLUSIONS: The point-of-care immunoassay test provides improved diagnostic accuracy for the detection of ROM compared to fern testing. It has the potential of improving patient management decisions, thereby minimizing serious complications and perinatal morbidity. PMID- 27199580 TI - Health Promotion and Health Behaviors of Diverse Ethnic/Racial Women Cosmetologists: A Review. AB - Women from diverse ethnic/racial backgrounds have higher chronic disease mortality rates when compared to White non-Hispanic women. Community-based programs, such as beauty salons, have been used to reach diverse ethnic/racial women, yet little is known about diverse ethnic/racial women cosmetologists' involvement in health promotion and their health behaviors, which is the purpose of this review. The growing beauty salon health promotion literature indicates that their roles in these studies have been varied, not only as health promoters but also as recruiters, facilitators, and in general major catalysts for investigator-initiated studies. However, the review also identified a major void in the literature in that there were few studies on health behaviors of diverse ethnic/racial women cosmetologists, especially African American women cosmetologists. Recommendations include increasing the capacity of diverse ethnic/racial women cosmetologists as community health leaders and investigating their health status, knowledge, attitudes, and practices. PMID- 27199581 TI - A revision of the genus Muricea Lamouroux, 1821 (Anthozoa, Octocorallia) in the eastern Pacific. Part II. AB - The species of the genus Muricea were mainly described from 1846 to 1870. After that very few contributions were published. Although the highest richness of Muricea species is in the eastern Pacific shallow waters, a comprehensive systematic study of the genus does not exist. Recently we started a taxonomic review of the genus in order to validate the status of four species previously included in the genus Eumuricea. Herein we present the second part of the Muricea revision dealing with the species-group characterised by shelf-like calyces instead of tubular-like calyces (the Muricea squarrosa-group). Original type material was morphologically analysed and illustrated using optical and scanning electron microscopy. Comparative character tables are provided for the genus. The taxonomic status of the species was analysed and established by designating lectotypes, alternatively by recognising a holotype by monotypy. We conclude that the genus Muricea comprises 20 valid species, including the previous four in the Muricea squarrosa-group. We propose 10 lectotypes, a new combination and three more species groups for the genus based on morphology: the Muricea fruticosa group, Muricea plantaginea-group and Muricea austera-group. PMID- 27199582 TI - Sinularia polydactyla (Ehrenberg, 1834) (Cnidaria, Octocorallia) re-examined, with the description of a new species. AB - Sinularia polydactyla (Ehrenberg, 1834) is re-described and a lectotype assigned. This led to examination of related material from various Indo-Pacific regions. Consequently, Sinularia levi sp. n. is described from Eilat, Israel (Gulf of Aqaba, northern Red Sea) and Sinularia compressa Tixier-Durivault, 1945 and Sinularia candidula Verseveldt and Benayahu, 1983 are synonymized with Sinularia polydactyla. Additional specimens identified in the literature as Sinularia polydactyla are provisionally reassigned to other taxa. PMID- 27199583 TI - A new species of Bothriembryon (Mollusca, Gastropoda, Bothriembryontidae) from south-eastern Western Australia. AB - Bothriembryon sophiarum sp. n. is described, based on shell and anatomical morphology, from the coastal area of south-easternmost Western Australia. This is the first description of a new extant Australian bothriembryontid in 33 years. The shell of Bothriembryon sophiarum is slender with a unique teleoconch sculpture. It is found in low coastal scrub on cliff edges and escarpments and because of its restricted distribution, qualifies as a short range endemic. PMID- 27199584 TI - A new species of Anomognathus and new Canadian and provincial records of aleocharine rove beetles from Alberta, Canada (Coleoptera, Staphylinidae, Aleocharinae). AB - A new species, Anomognathus athabascensis Klimaszewski, Hammond & Langor, sp. n., and nine new provincial records including one new country record of aleocharine beetles are presented for the province of Alberta. Diagnostics, images of habitus and genital structures, distribution, natural history information and new locality data are provided for the newly recorded species. A checklist for all recorded aleocharines from Alberta is updated. PMID- 27199585 TI - First record of Streptosyllis nunezi Faulwetter et al., 2008 (Annelida, Syllidae) from the United Kingdom, and amendment to the genus Streptosyllis Webster & Benedict, 1884. AB - During a benthic survey of a Marine Conservation Zone located on the Skerries Bank in the English Channel off the south-west coast of England, three specimens of Streptosyllis nunezi Faulwetter et al., 2008 were found. This is the second ever record of the species after its original description, and the first record from waters around the U.K. and a significant northerly range extension for a species previously only recorded from the Canary Islands and the Mediterranean Sea. A single simple ventral chaeta in each of the two posterior-most segments was discovered in this and two other species of Streptosyllis Webster & Benedict, 1884. The generic definition of Streptosyllis is emended to include this feature previously unknown for the genus, and an updated key to the Streptosyllis found in UK waters is provided. PMID- 27199586 TI - Systematics of testudacarine torrent mites (Acari, Hydrachnidia, Torrenticolidae) with descriptions of 13 new species from North America. AB - Thirteen new species of North American Testudacarus (Torrenticolidae: Testudacarinae) are described: Testudacarus deceptivus O'Neill & Dowling, sp. n., Testudacarus hitchensi O'Neill & Dowling, sp. n., Testudacarus harrisi O'Neill & Dowling, sp. n., Testudacarus dennetti O'Neill & Dowling, sp. n., Testudacarus dawkinsi O'Neill & Dowling, sp. n., Testudacarus radwellae O'Neill & Dowling, sp. n., Testudacarus kirkwoodae O'Neill & Dowling, sp. n., Testudacarus hyporhynchus O'Neill & Dowling, sp. n., Testudacarus smithi O'Neill & Dowling, sp. n., Testudacarus rollerae O'Neill & Dowling, sp. n., Testudacarus elongatus O'Neill & Dowling, sp. n., Testudacarus rectangulatus O'Neill & Dowling, sp. n., and Testudacarus oblongatus O'Neill & Dowling, sp. n. Testudacarus vulgaris Habeeb, 1954 is resurrected from synonymy with Testudacarus minimus and redescribed. Debsacarus (Habeeb, 1961), Testudacarus americanus Marshall, 1943, and Testudacarus minimus Marshall, 1943 are redescribed. All redescriptions are from original types. Species delimination was accomplished through examination of morphology, biogeography, and molecular phylogenetics of the barcoding region of COI. Other species are addressed and a key to world species is presented. For Testudacarinae, this represents the first published: 1) descriptions from multiple specimens (i.e. intraspecific variation); 2) colored photographs; 3) explicit illustrations and discussion of sexual dimorphism within the subfamily; 4) genetic data. A comprehensive testudacarine reference list is also included. PMID- 27199587 TI - DNA barcoding reveals polymorphism in the pygmy grasshopper Tetrix bolivari (Orthoptera, Tetrigidae). AB - Many pygmy grasshopper species exhibit colour-marking polymorphism. However, this polymorphism in some species, such as Tetrix bolivari, is almost unknown. The aim of this work is to identify using DNA barcoding the colour-marking polymorphic morphs of this pygmy grasshopper species collected from both grass and sand microhabitats. Analysis by NJ clustering and pairwise distances indicated that all specimens collected showing colour-marking polymorphism are species of Tetrix bolivari. Haplotype network construction showed ten different haplotypes from a total of 57 Tetrix bolivari individuals with H1(82.5%) being the most common type and it also displayed low divergence within Tetrix bolivari population. The haplotype analyses were consistent with the NJ clustering. Our field census showed the frequency of Tetrix bolivari morphs differed significantly, with the rank order of morphs (from high to low) typeA1, type B1, type A2, type A3, type A4, type A5, type A6, type A7, type B2, type B3, and type B4. The most common type A morphs were without contrasting markings, while the rarer type B morphs have contrasting white markings. We suggest that type B morphs have greater camouflage effects against natural backgrounds such as grass or sand than type A morphs. Both our field census and haplotype analysis revealed that type A has higher frequency and more haplotypes than type B. PMID- 27199588 TI - Aspilota isfahanensis, a new species of the genus Aspilota Foerster, 1863 from Iran (Hymenoptera, Braconidae, Alysiinae). AB - A new species of Aspilota without mesoscutal pit, Aspilota isfahanensis Peris Felipo, sp. n., is described and illustrated from Iran. The new species is compared with its three morphologically most similar species, Aspilota compressiventris Stelfox & Grahan, 1951, Aspilota makita Papp, 2008 and Aspilota spiracula Munk & Peris-Felipo, 2013, is provided. A key to the western Asian species of Aspilota is provided. PMID- 27199589 TI - Four new species of Trigonopterus Fauvel from the island of New Britain (Coleoptera, Curculionidae). AB - The hyperdiverse genus Trigonopterus has its center of diversity in Melanesia, but only a single species is recorded from the Bismarck Archipelago to date. Here we describe four new species from the island of New Britain: Trigonopterus chewbacca sp. n., Trigonopterus obsidianus sp. n., Trigonopterus puncticollis sp. n. and Trigonopterus silaliensis sp. n. We provide cytochrome oxidase subunit I (cox1) sequences of the new species and a key to all five species known from the Bismarck Archipelago. PMID- 27199590 TI - Ancient Himalayan wolf (Canis lupus chanco) lineage in Upper Mustang of the Annapurna Conservation Area, Nepal. AB - The taxonomic status of the wolf (Canis lupus) in Nepal's Trans-Himalaya is poorly understood. Recent genetic studies have revealed the existence of three lineages of wolves in the Indian sub-continent. Of these, the Himalayan wolf, Canis lupus chanco, has been reported to be the most ancient lineage historically distributed within the Nepal Himalaya. These wolves residing in the Trans Himalayan region have been suggested to be smaller and very different from the European wolf. During October 2011, six fecal samples suspected to have originated from wolves were collected from Upper Mustang in the Annapurna Conservation Area of Nepal. DNA extraction and amplification of the mitochondrial (mt) control region (CR) locus yielded sequences from five out of six samples. One sample matched domestic dog sequences in GenBank, while the remaining four samples were aligned within the monophyletic and ancient Himalayan wolf clade. These four sequences which matched each other, were new and represented a novel Himalayan wolf haplotype. This result confirms that the endangered ancient Himalayan wolf is extant in Nepal. Detailed genomic study covering Nepal's entire Himalayan landscape is recommended in order to understand their distribution, taxonomy and, genetic relatedness with other wolves potentially sharing the same landscape. PMID- 27199591 TI - Iranian terrestrial isopods of the family Cylisticidae Verhoeff, 1949 with a description of a new species (Isopoda, Oniscidea). AB - In the present study, the terrestrial isopods of the family Cylisticidae in Iran are investigated. Geographical distributions of two formerly reported species from Iran, namely Cylisticoides angulatus Schmalfuss, 2003 and Cylisticus rotundifrons (Schmalfuss, 1986), are expanded. Cylisticus masalicus sp. n. is described and its diagnostic characters are figured. PMID- 27199592 TI - Description and life-cycle of Taenia lynciscapreoli sp. n. (Cestoda, Cyclophyllidea). AB - A new species of tapeworm, Taenia lynciscapreoli sp. n. (Cestoda, Cyclophyllidea), is described from the Eurasian lynx (Lynx lynx), the main definitive host, and the roe deer (Capreolus capreolus and Capreolus pygargus), the main intermediate hosts, from Finland and Russia (Siberia and the Russian Far East). The new species was found once also in the wolf (Canis lupus) and the Eurasian elk/moose (Alces alces), representing accidental definitive and intermediate hosts, respectively. The conspecificity of adult specimens and metacestodes of Taenia lynciscapreoli sp. n. in various host species and regions, and their distinction from related species of Taenia, was confirmed by partial nucleotide sequences of the mitochondrial cytochrome c oxidase subunit 1 gene. Morphologically, Taenia lynciscapreoli sp. n. can be separated unambiguously from all other species of Taenia by the shape of its large rostellar hooks, particularly the characteristically short, wide and strongly curved blade. If the large rostellar hooks are missing, Taenia lynciscapreoli may be separated from related species by a combination of morphological features of mature proglottids. It is suggested that Taenia lynciscapreoli has been present in published materials concerning the tapeworms of Lynx lynx and Lynx pardinus in Europe, but has been misidentified as Taenia pisiformis (Bloch, 1780). Taenia lynciscapreoli sp. n. has not been found in lynx outside the range of roe deer, suggesting a transmission pathway based on a specific predator-prey relationship. The present study applies a novel, simple approach to compare qualitative interspecific differences in the shape of rostellar hooks. PMID- 27199593 TI - Revision of sinistral land snails of the genus Camaena (Stylommatophora, Camaenidae) from China based on morphological and molecular data, with description of a new species from Guangxi, China. AB - The camaenid land snail genus Camaena is widely distributed throughout Southeast Asia. Thirteen species are found in China alone. Among these, Camaena cicatricosa (Muller, 1774) is the most widely distributed species, including four subspecies, Camaena cicatricosa ducalis (Ancey, 1885), Camaena cicatricosa inflata (Mollendorff, 1885), Camaena cicatricosa obtecta (Fischer, 1898) and Camaena cicatricosa connectens (Dautzenberg & Fischer, 1906). The systematics of these taxa is revised herein based on comparative shell morphology and anatomy as well as analyses of DNA sequences of two mitochondrial genes (COI, 16S rRNA) and one nuclear marker, ITS2. We found that all subspecies form well-supported clades in a molecular phylogeny and are well-differentiated from each other by genetic distances that are consistent with amounts of interspecific differentiation. In addition, they clearly differ from each other in reproductive features. Based on these observations, we elevate all four subspecies to the rank of full species. Moreover, based on morphological and mitochdondrial differentiation, we describe a new species, Camaena poyuensis sp. n. from Guangxi, China. The new species conspicuously differs from its sibling species Camaena cicatricosa in having a larger and more depressed shell, a completely covered umbilicus, more or less purplish peristome, an obtuse angle at the junction of the basal and columellar lip, longer pedunculus of the bursa copulatrix, thicker epiphallus and penis, and short conic verge. Previous named species are also redescribed on their shell and anatomical characters, because the original descriptions are uninformative. PMID- 27199594 TI - Pseudouroctonus maidu, a new species of scorpion from northern California (Scorpiones, Vaejovidae). AB - A new species of vaejovid scorpion from northern California, Pseudouroctonus maidu sp. n., is named and described. This new species appears to be most similar to Pseudouroctonus iviei (Gertsch & Soleglad, 1972) and Pseudouroctonus glimmei (Hjelle, 1972). PMID- 27199595 TI - Three new species of mealybug (Hemiptera, Coccomorpha, Pseudococcidae) on persimmon fruit trees (Diospyros kaki) in southern Brazil. AB - Brazil has the greatest insect diversity in the world; however, little is known about its scale insect species (Hemiptera: Coccomorpha). Mealybugs (Pseudococcidae) have been found in at least 50% of persimmon orchards Diospyros kaki L. in the southern part of the country. In this study three new mealybug species on persimmon trees located in the Serra Gaucha Region, RS, Brazil, namely, Anisococcus granarae Pacheco da Silva & Kaydan, sp. n., Ferrisia kaki Kaydan & Pacheco da Silva, sp. n. and Pseudococcus rosangelae Pacheco da Silva & Kaydan, sp. n. are described. In addition, an identification key for the genera occurring on fruit orchards and vineyards in Brazil is provided, together with illustrations and molecular data for the new species. PMID- 27199596 TI - Description of three new species of Arescon Walker (Hymenoptera, Mymaridae) from China. AB - Three new species of Arescon Walker, 1846, Arescon gaoligongensis Jin & Li, sp. n., Arescon sparsiciliatus Jin & Li, sp. n. and Arescon stenopterus Jin & Li, sp. n. are described. A key to the Chinese species is given and photomicrographs are provided to illustrate morphological characters. All the specimens are deposited in the insect collections of Northeast Forestry University, China. PMID- 27199597 TI - Keylimepie peckorum gen. n. and sp. n., (Hymenoptera, Braconidae) from southern Florida, U.S., the first known brachypterous member of the subfamily Microgastrinae. AB - Keylimepie peckorum Fernandez-Triana, gen. n. and sp. n., are described from southern Florida, U.S. Females have the shortest wings (0.6-0.7 * body length) of any known microgastrine wasp. The genus can also be recognized on features of the head, propodeum and first three metasomal tergites. All specimens were collected in hammock forests of the Florida Keys and Everglades National Park, but their host caterpillar is unknown. Because its morphology is unique and it is the first new microgastrine genus discovered in North America since 1985, the potential for future conservation of the species is discussed. PMID- 27199598 TI - Major range extensions for two genera of the parasitoid subtribe Facitorina, with a new generic synonymy (Braconidae, Rogadinae, Yeliconini). AB - The genera Conobregma van Achterberg and Facitorus van Achterberg are recorded from the Afrotropical region and the Indian subcontinent, respectively, for the first time, and two new species are described and illustrated: Conobregma bradpitti Quicke & Butcher, sp. n. from South Africa and Facitorus nasseri Ranjith & Quicke, sp. n. from India. Conobregma bradpitti sp. n. is intermediate between Conobregma which was described originally from the New World, and Asiabregma Belokobylskij, Zaldivar-Riveron & Maeto, which was coined for the S. E. Asian and East Palaearctic (Japanese) species described under the name Conobregma, plus more recently discovered taxa, but the differences between these genera are few and slight. Of the four previously proposed diagnostic characters for separating Asiabregma from Conobregma, the new species shares two with each, and therefore, the two genera are formally synonymised. Facitorus was previously known only from the East Palaearctic region and from S. E. Asia (Japan, Nepal, Taiwan and Vietnam). PMID- 27199599 TI - A new species of alpine Apenetretus Kurnakov from Taiwan: evidences from DNA barcodes and morphological characteristics (Coleoptera, Carabidae, Patrobini). AB - There are three isolated mountain ranges in Taiwan including Hsueshan Range, Central Mountain Range, and Yushan Range. The rise of these mountains has resulted in the isolation of some species and caused allopatric distribution resulting in divergence and speciation events of high mountain carabids, especially the flightless carabids such as Epaphiopsis, Apenetretus, and partial Nebria. Genus Apenetretus Kurnakov (1960) is typically distributed in high mountain areas of Taiwan. Three of the currently known Apenetretus species have been described from different mountain ranges. These species include Apenetretus yushanensis Habu, Apenetretus nanhutanus Habu, and Apenetretus smetanai Zamotajlov and Sciaky. In this study, a new species is described from Hsueshan, a mountain separated from the ranges of the previous known species, Apenetretus hsueshanensis sp. n. A key to the Taiwanese Apenetretus is included. A reconstructed phylogeny of the Taiwanese Apenetretus is introduced with the use of mitochondrial cytochrome c oxidase subunit I (COI) gene. Molecular data and geographical distribution of Apenetretus support the morphological characteristics observed among those mountain-isolated species and confirms the new species as being distinctly different. Moreover, lineage calibration suggests that the southern Apenetretus yushanensis is the most distant one compared to the other three northern Apenetretus at ca. 1.81 million years ago (mya), while the divergence time of Apenetretus hsueshanensis to its sister group was dated to 0.94 mya. PMID- 27199600 TI - What Azure blues occur in Canada? A re-assessment of Celastrina Tutt species (Lepidoptera, Lycaenidae). AB - The identity of Celastrina species in eastern Canada is reviewed based on larval host plants, phenology, adult phenotypes, mtDNA barcodes and re-assessment of published data. The status of the Cherry Gall Azure (Celastrina serotina Pavulaan & Wright) as a distinct species in Canada is not supported by any dataset, and is removed from the Canadian fauna. Previous records of this taxon are re-identified as Celastrina lucia (Kirby) and Celastrina neglecta (Edwards). Evidence is presented that both Celastrina lucia and Celastrina neglecta have a second, summer-flying generation in parts of Canada. The summer generation of Celastrina lucia has previously been misidentified as Celastrina neglecta, which differs in phenology, adult phenotype and larval hosts from summer Celastrina lucia. DNA barcodes are highly conserved among at least three North American Celastrina species, and provide no taxonomic information. Celastrina neglecta has a Canadian distribution restricted to southern Ontario, Manitoba, Saskatchewan and easternmost Alberta. The discovery of museum specimens of Celastrina ladon (Cramer) from southernmost Ontario represents a new species for the Canadian butterfly fauna, which is in need of conservation status assessment. PMID- 27199601 TI - DNA barcoding and morphological analyses revealed validity of Diadema clarki Ikeda, 1939 (Echinodermata, Echinoidea, Diadematidae). AB - A long-spined sea urchin Diadema-sp reported from Japanese waters was genetically distinct from all known Diadema species, but it remained undescribed. Extensive field surveys in Japan with molecular identification performed in the present study determined five phenotypes (I to V) in Diadema-sp according to the presence and/or shape of a white streak and blue iridophore lines in the naked space of the interambulacral area. All phenotypes were distinct from Diadema setosum (Leske, 1778) and Diadema savignyi (Audouin, 1829), of which a major type (I) corresponded to Diadema clarki Ikeda, 1939 that was questioned and synonymized with Diadema setosum by Mortensen (1940). The holotype of Diadema clarki has not been found, but three unlabeled dried tests of Diadema were found among Ikeda's original collection held in the Kitakyushu Museum of Natural History and Human History, Fukuoka, Japan. A short mtDNA COI fragment (ca. 350bp) was amplified from one of the tests, and the nucleotide sequence determined (275bp) was nearly identical with that of Diadema-sp. Arrangements of the primary tubercles on the coronal plates in Diadema-sp and the museum specimen also conformed with Diadema clarki, indicating that Diadema-sp is identical to Diadema clarki and a valid species. Narrow latitudinal distribution (31 degrees N to 35 degrees N) of Diadema clarki in Japan was observed, where it co-existed with abundant Diadema setosum and rare Diadema savignyi. No Diadema clarki was found in the southern islands in Japan, such as Satsunan Islands to Ryukyu Islands and Ogasawara Island, where Diadema setosum and Diadema savignyi were commonly observed. PMID- 27199602 TI - Redescription and designation of a neotype for Caecum floridanum (Littorinimorpha, Truncatelloidea, Caecidae) with a characterization of the protoconch and growth stages. AB - After an extensive search for the type specimens of Caecum floridanum Stimpson, 1851, we believe that these specimens may have been either lost or destroyed in the Chicago fire (1871). This paper presents a redescription of the species and a neotype is designated based on material from the type locality (Florida). Protoconch and growth stages of Caecum floridanum are described and illustrated herein. The teleoconch IV of Caecum floridanum is characterized by strong, wide, low, rounded, closely arranged axial ribs, except last three to four preceding the aperture, which are larger and more widely separated. Caecum compactum Dall, 1892 is here synonymized under Caecum floridanum. Caecum annulatum Emmons, 1858 and Caecum dux Folin, 1871 are not considered synonyms of Caecum floridanum in this report. PMID- 27199603 TI - Papiliocoelotes gen. n., a new genus of Coelotinae (Araneae, Agelenidae) spiders from the Wuling Mountains, China. AB - One new genus of the spider subfamily Coelotinae, Papiliocoelotes gen. n., with five new species is described for both sexes: Papiliocoelotes guanyinensis sp. n., Papiliocoelotes guitangensis sp. n., Papiliocoelotes jiepingensis sp. n., Papiliocoelotes meiyuensis sp. n., Papiliocoelotes yezhouensis sp. n. All new species were collected from caves in the Wuling Mountains of Hubei and Hunan Provinces, China. DNA barcodes were obtained for future use. PMID- 27199604 TI - Megastigmus seed chalcids (Hymenoptera, Torymidae) radiated much more on Angiosperms than previously considered. I- Description of 8 new species from Kenya, with a key to the females of Eastern and Southern Africa. AB - A survey of seed chalcids from woody plants in Kenya revealed 12 species belonging to the genus Megastigmus Dalman, 1820, and has increased to 16 the number of Megastigmus species presently recorded from the Afrotropical Region, of which at least 13 are seed feeders. A key to female Megastigmus of the Afrotropical Region is provided. Eight new species are described from morphological evidence: Megastigmus lanneae Roques & Copeland, Megastigmus laventhali Roques & Copeland, Megastigmus ozoroae Roques & Copeland, and Megastigmus smithi Roques & Copeland in seeds of species of the family Anacardiaceae, Megastigmus copelandi Roques & Copeland and Megastigmus grewianae Roques & Copeland in seeds of Malvaceae, Megastigmus helinae Roques & Copeland in seeds of Rhamnaceae, and Megastigmus icipeensis Roques & Copeland for which no host is known. These collections include the first records of Malvaceae and Rhamnaceae as hosts of Megastigmus seed chalcids, which appear to have radiated in Angiosperms much more than previously considered. Analyses of the mitochondrial (cytochrome oxidase subunit one - COI) and nuclear DNA (28S ribosomal region) could be carried out on 8 of the 16 African species of which 5 were newly described ones. The species associated with Anacardiaceae always clustered together in phylogenies, confirming the existence of a strong and ancestral monophyletic clade, unlike the ones associated with Malvaceae and Rhamnaceae, whose position remains unclear. All holotypes are deposited in the National Museums of Kenya. PMID- 27199605 TI - Records of Limoniidae and Pediciidae (Diptera) from Armenia, with the first Armenian checklist of these families. AB - Records of species of the families Limoniidae and Pediciidae are presented from Armenia. A total of 38 species of Limoniidae and four species of Pediciidae are listed. Of these, 27 species of Limoniidae and one species of Pediciidae represent the first records from Armenia. The first checklist of these families from Armenia is appended, containing 77 species of Limoniidae and six species of Pediciidae. PMID- 27199606 TI - A database on the distribution of butterflies (Lepidoptera) in northern Belgium (Flanders and the Brussels Capital Region). AB - In this data paper, we describe two datasets derived from two sources, which collectively represent the most complete overview of butterflies in Flanders and the Brussels Capital Region (northern Belgium). The first dataset (further referred to as the INBO dataset - http://doi.org/10.15468/njgbmh) contains 761,660 records of 70 species and is compiled by the Research Institute for Nature and Forest (INBO) in cooperation with the Butterfly working group of Natuurpunt (Vlinderwerkgroep). It is derived from the database Vlinderdatabank at the INBO, which consists of (historical) collection and literature data (1830 2001), for which all butterfly specimens in institutional and available personal collections were digitized and all entomological and other relevant publications were checked for butterfly distribution data. It also contains observations and monitoring data for the period 1991-2014. The latter type were collected by a (small) butterfly monitoring network where butterflies were recorded using a standardized protocol. The second dataset (further referred to as the Natuurpunt dataset - http://doi.org/10.15468/ezfbee) contains 612,934 records of 63 species and is derived from the database http://waarnemingen.be, hosted at the nature conservation NGO Natuurpunt in collaboration with Stichting Natuurinformatie. This dataset contains butterfly observations by volunteers (citizen scientists), mainly since 2008. Together, these datasets currently contain a total of 1,374,594 records, which are georeferenced using the centroid of their respective 5 * 5 km2 Universal Transverse Mercator (UTM) grid cell. Both datasets are published as open data and are available through the Global Biodiversity Information Facility (GBIF). PMID- 27199607 TI - New species in the Sitalcina sura species group (Opiliones, Laniatores, Phalangodidae), with evidence for a biogeographic link between California desert canyons and Arizona sky islands. AB - The western United States is home to numerous narrowly endemic harvestman taxa (Arachnida, Opiliones), including members of the genus Sitalcina Banks, 1911. Sitalcina is comprised of three species groups, including the monospecific Sitalcina californica and Sitalcina lobata groups, and the Sitalcina sura group with eight described species. All species in the Sitalcina sura group have very small geographic distributions, with group members distributed like disjunct "beads on a string" from Monterey south to southern California and southeast to the sky-island mountain ranges of southern Arizona. Here, molecular phylogenetic and species delimitation analyses were conducted for all described species in the Sitalcina sura group, plus several newly discovered populations. Species trees were reconstructed using multispecies coalescent methods implemented in *BEAST, and species delimitation was accomplished using Bayes Factor Delimitation (BFD). Based on quantitative species delimitation results supported by consideration of morphological characters, two new species (Sitalcina oasiensis sp. n., Sitalcina ubicki sp. n.) are described. We also provide a description of the previously unknown male of Sitalcina borregoensis Briggs, 1968. Molecular phylogenetic evidence strongly supports distinctive desert versus coastal clades, with desert canyon taxa from southern California more closely related to Arizona taxa than to geographically proximate California coastal taxa. We hypothesize that southern ancestry and plate tectonics have played a role in the diversification history of this animal lineage, similar to sclerophyllous plant taxa of the Madro-Tertiary Geoflora. Molecular clock analyses for the Sitalcina sura group are generally consistent with these hypotheses. We also propose that additional Sitalcina species await discovery in the desert canyons of southern California and northern Baja, and the mountains of northwestern mainland Mexico. PMID- 27199608 TI - New species of Austropurcellia, cryptic short-range endemic mite harvestmen (Arachnida, Opiliones, Cyphophthalmi) from Australia's Wet Tropics biodiversity hotspot. AB - The genus Austropurcellia is a lineage of tiny leaf-litter arachnids that inhabit tropical rainforests throughout the eastern coast of Queensland, Australia. The majority of their diversity is found within the Wet Tropics rainforests of northeast Queensland, an area known for its exceptionally high levels of biodiversity and endemism. Studying the biogeographic history of limited dispersal invertebrates in the Wet Tropics can provide insight into the role of climatic changes such as rainforest contraction in shaping rainforest biodiversity patterns. Here we describe six new species of mite harvestmen from the Wet Tropics rainforests, identified using morphological data, and discuss the biogeography of Austropurcellia with distributions of all known species. With this taxonomic contribution, the majority of the known diversity of the genus has been documented. PMID- 27199609 TI - Position of the dentifera-group in the Coronatella-branch and its relocation to a new genus: Magnospina gen. n. (Crustacea, Chydoridae, Aloninae). AB - Magnospina gen. n. was created to relocate species of the dentifera-group from Alona sensu lato (Crustacea: Cladocera) and include Magnospina dentifera comb. n. and Magnospina siamensis comb. n. The synapomorphies of the Magnospina gen. n. are (1) basal spines longer than 2/3 of the postabdominal claw, (2) presence of 1 4 large denticles, broad at their bases, protruding downwards, without setules between them. Morphological traits such as habitus, rostrum and postabdomen shape, armature of IDL setae, number of setae on the exopod of limb III are also important in the distinction between Magnospina gen. n. and other genera from the Coronatella-branch. The morphology of Magnospina dentifera comb. n. male confirms the closer relationship with the clade composed by the elgans-group from Alona sensu lato, Ovalona and Leberis, but the external morphology, morphology of the postabdominal claw, basal spine and setae 2-3 of IDL support their separation from any of the group cited. It is concluded that the Coronatella-lineage of Aloninae is composed of the genera Coronatella, Anthalona, Karualona, Bergamina, Extremalona, Ovalona, Celsinotum, Leberis and Magnospina gen. n. The elegans group from Alona sensu lato also belongs to Coronatella-lineage, but still need formal allocation. PMID- 27199610 TI - The larvae of the European species of genus Apataniana Mosely, 1936 (Trichoptera, Apataniidae): descriptions, key and ecology. AB - This paper describes the previously unknown or insufficiently known larvae of Apataniana hellenica, Apataniana stropones and Apataniana vardusia. Species association was enabled by the fact that the three micro-endemic Apataniana larvae are restricted to Greece and the only Apataniidae species recorded in European ecoregion 6 (Hellenic Western Balkan; Graf et al. 2008), and that the endemic status of the three species clearly defined their non-overlapping sampling ranges. Information on the morphology of the larvae is given, and the most important diagnostic features are illustrated. PMID- 27199611 TI - Taxonomic notes relating to Glenea diversenotata Schwarzer and G. quadriguttata Pic (Coleoptera, Cerambycidae, Lamiinae). AB - Glenea diversenotata Schwarzer, 1925 is reinstated from a subspecies of Glenea tonkinea Aurivillius, 1925 to species level and Glenea neohumerosa Lin & Yang, 2011 is a new junior synonym. Some biological information on Glenea diversenotata is recorded for the first time, including pictures of the larva and pupa. Glenea quadriguttata Pic, 1926 is reinstated from a subspecies of Glenea lacteomaculata Schwarzer, 1925 to species level. Lectotypes for Glenea lacteomaculata and Glenea quadriguttata are designated. A modified key to the related species is presented. PMID- 27199612 TI - A new genus and species of leaf-mining moth from the French Alps, Mercantouria neli gen. n., sp. n. (Lepidoptera, Gracillariidae). AB - The Alps are a hotspot of biodiversity in Europe with many Lepidoptera species still to be discovered. Here we describe a new gracillariid genus and species, Mercantouria neli gen. n. and sp. n. The morphology of the male genitalia is highly differentiated with unique features. DNA barcodes show that its nearest neighbor is the North American species 'Caloptilia' scutellariella (Braun, 1923). Mercantouria neli is known from four adults (two males and two females) collected at two localities in the French Alps. Its host plant and life cycle remain unknown. PMID- 27199613 TI - Extracorporeal Irradiation and Reimplantation with Total Hip Arthroplasty for Periacetabular Pelvic Resections: A Review of 9 Cases. AB - We report the early results of nine patients with periacetabular malignancies treated with Enneking and Dunham type 2 resection and reconstruction using extracorporeally irradiated (ECI) tumour bone combined with total hip arthroplasty (THA). Diagnosis was chondrosarcoma in six patients, osteosarcoma in two patients, and metastatic renal cell carcinoma in one patient. All patients underwent surgical resection and the resected specimen was irradiated with 50 Gy in a single fraction before being prepared for reimplantation as a composite autograft. The mean follow-up was 21 months (range, 3-59). All patients were alive at latest follow-up. No local recurrence was observed. One patient serially developed three pulmonary metastases, all of which were resected. One experienced hip dislocation due to incorrect seating of an acetabular liner. This was successfully treated with revision of the liner with no further episodes of instability. There were no cases of deep infection or loss of graft. The average Musculoskeletal Tumor Society (MSTS) score was 75% (range, 57-87%). Type 2 pelvic reconstruction with ECI and THA has shown excellent early oncological and functional results in our series. Preservation of the gluteus maximus and hip abductors is important for joint stability and prevention of infection. PMID- 27199615 TI - Automated classification of vessel disease based on high-resolution intravascular multi-parametric mapping MRI. PMID- 27199614 TI - Multi-parametric MRI Assessment of Tumor Response to High-Intensity Focused Ultrasound in a Rat Glioma Model. PMID- 27199617 TI - Exploring the Reasons Behind Parental Refusal of Vaccines. AB - Parental refusal of vaccines is a growing a concern for the increased occurrence of vaccine preventable diseases in children. A number of studies have looked into the reasons that parents refuse, delay, or are hesitant to vaccinate their child(ren). These reasons vary widely between parents, but they can be encompassed in 4 overarching categories. The 4 categories are religious reasons, personal beliefs or philosophical reasons, safety concerns, and a desire for more information from healthcare providers. Parental concerns about vaccines in each category lead to a wide spectrum of decisions varying from parents completely refusing all vaccinations to only delaying vaccinations so that they are more spread out. A large subset of parents admits to having concerns and questions about childhood vaccinations. For this reason, it can be helpful for pharmacists and other healthcare providers to understand the cited reasons for hesitancy so they are better prepared to educate their patients' families. Education is a key player in equipping parents with the necessary information so that they can make responsible immunization decisions for their children. PMID- 27199616 TI - Pubertal Maturation Compression and Behavioral Impulsivity among Boys at Increased Risk for Substance Use. AB - OBJECTIVES: While early onset of puberty among girls has been related to substance use involvement and other adverse outcomes, less research has examined pubertal development and outcomes in boys. Further, research on puberty has not been conducted in the context of other risk factors for substance use involvement such as impulsivity. To address these gaps, this study characterized boys' pubertal development from preadolescence to mid-adolescence and related it to substance use risk and behavioral impulsivity. METHODS: A sample of 153 boys completed the Pubertal Development Scale to assess perception of their pubertal development relative to same age peers from ages 10 to 16 years, at 6-month intervals. Group-based trajectory modeling identified three distinct patterns of pubertal development: boys with more slowly developing boys with either earlier (n = 54) or later (n = 43) pubertal timing, and boys with faster tempo of pubertal development (n = 56). The groups were compared on demographic and substance use risk characteristics, as well as behavioral measures of impulsivity. RESULTS: Boys who had the accelerated progression through puberty had the highest proportion of family histories of substance use disorder and perform more impulsively on reward choice measures. CONCLUSIONS: Outcomes are consistent within the Maturation Compression Hypothesis and social neuroscience models of adolescent developmental risk. PMID- 27199618 TI - Beyond Susceptible and Resistant, Part III: Treatment of Infections due to Gram Negative Organisms Producing Carbapenemases. AB - Carbapenemases are enzymes that are capable of inactivating all or almost all beta-lactam antimicrobial agents. These enzymes are frequently coexpressed with other resistance mechanisms to non-beta-lactams, leading to extremely drug resistant pathogens. Once a curiosity, these enzymes have spread into organisms that are among the most common causes of infection, such as Klebsiella pneumoniae and Escherichia coli. Identification of these organisms has proved challenging for clinical microbiology laboratories, leading to revisions in susceptibility standards for carbapenems. Although currently a rare cause of infection in children, these carbapenem-resistant Enterobacteriaceae (CRE) are becoming endemic in a variety of healthcare settings. Management of infections due to CRE is complicated by a lack of effective treatment options and clinical data on their effectiveness. Treatment of CRE infections in children is particularly challenging because therapeutic options for CRE lack adequate data on dosing and safety in children. Use of unconventional combination treatment regimens, including agents to which the organism is resistant in vitro, may provide some benefit in the treatment of severe CRE infection. Fortunately, several agents with the potential for treatment of CRE infections have been recently approved or are in late clinical development, although few data will be available in the short term to inform use in children. PMID- 27199620 TI - Identification of Risk Factors for Elevated Neonatal Gentamicin Trough Concentrations. AB - OBJECTIVES: The objective of this study was to identify neonatal and maternal characteristics that may be associated with elevated neonatal gentamicin trough concentrations despite application of a previously published gentamicin dosage strategy. METHODS: Retrospective cohort study of all neonates admitted to University of Vermont Medical Center (562-bed academic teaching hospital, Burlington, VT) receiving gentamicin between June 1, 2009, and August 31, 2013. A total of 205 neonates were included, with 41 cases and 164 controls. RESULTS: Postmenstrual age (PMA, gestational age plus chronological age) and small-for gestational age (SGA) status were independently associated with elevated neonatal gentamicin trough concentrations. No maternal risk factor evaluated remained significantly associated in the multivariate analysis. CONCLUSIONS: The probability of an elevated gentamicin trough concentration increases with lower PMA and is further accentuated in neonates with SGA status. In contrast, the presence of maternal risk factors did not increase the likelihood of elevated gentamicin trough concentrations. Neonates with lower PMA and SGA status may require an individualized dosage and monitoring strategy. PMID- 27199619 TI - Pharmacologic Treatment for Pediatric Gastroparesis: A Review of the Literature. AB - There have been a number of agents that have been tried for treatment of gastroparesis over the past 3 decades, with varying levels of success. Guidelines exist for the management of gastroparesis in adults; however, even though the cause of gastroparesis in children is similar to that in adults, no guidelines exist for treating pediatric gastroparesis as studies on the topic are limited. With what little information we have on pediatric gastroparesis, medications used in children's studies do not seem to demonstrate the same results as in adult patients with gastroparesis; thus, future studies of whether certain medications are effective for treating pediatric gastroparesis and at what dose still need to be conducted. Pharmacological treatment options for pediatric gastroparesis do not show a clear correlation of resolving or even maintaining gastroparesis associated symptoms or disease state. This article reviews the available studies of drugs that have shown some efficacy, with an emphasis on pediatric studies. PMID- 27199621 TI - Once Daily Dosing of Ceftriaxone and Metronidazole in Children With Perforated Appendicitis. AB - OBJECTIVES: The aim of this study was to compare hospital length of stay and rate of infectious complications in children with perforated appendicitis based on the postoperative antibiotic administered. METHODS: This study was a retrospective analysis of children with perforated appendicitis who underwent an appendectomy at a large academic medical center from 2008 to 2013. The primary outcome was hospital length of stay. The secondary outcomes were rates of abscess formation, wound infection, and 30-day readmissions. RESULTS: One hundred and twenty-three patients were included. Sixty-six patients (53%) were administered ceftriaxone and metronidazole once daily; 57 (47%) were administered other antibiotic regimens, which consisted of single, double, or triple antibiotic therapy with a beta-lactam backbone. There was no difference between the groups in terms of postoperative length of stay (5.7 versus 5.8 days, p = 0.83), postoperative abscess rate (8% versus 4%, p = 0.57), postoperative wound infection rate (5% versus 2%, p = 0.73), and 30-day readmissions (3% versus 11%, p = 0.19). CONCLUSIONS: While there was no statistically significant difierence in the outcomes evaluated, the rate of infectious complications was twofold higher in those given ceftriaxone and metronidazole than in others. A larger prospective randomized controlled trial is warranted to better understand the risks of using these agents. PMID- 27199622 TI - Comparison of Intravenous Palivizumab and Standard of Care for Treatment of Respiratory Syncytial Virus Infection in Mechanically Ventilated Pediatric Patients. AB - OBJECTIVES: Evidence suggests palivizumab may be beneficial for respiratory syncytial virus (RSV) infection in pediatric patients, although it is only approved by the US Food and Drug Administration for RSV prophylaxis. The objective of this study is to compare outcomes among pediatric patients with RSV infection who received intravenous palivizumab and standard of care versus standard of care alone. METHODS: This is a retrospective, single-center cohort study conducted between November 2003 and October 2013. Pediatric patients with active RSV infection treated with intravenous (IV) palivizumab after initiation of mechanical ventilation were matched 1:1 to a control selected from ventilated patients who received standard of care. The primary end point evaluated the duration of mechanical ventilation between groups. Secondary end points included hospital length of stay, intensive care unit length of stay, duration of respiratory support over baseline, time to RSV microbiologic cure, duration of antibiotic therapy, and in-hospital mortality. RESULTS: A total of 22 patients with a median age of 3 months were included in the study. Patients in the treatment group received a median of 2 doses of IV palivizumab, with a mean dose of 14.2 mg/kg. All patients received bronchodilators and corticosteroids, with the exception of 1 patient in the control group, and only 1 treatment group patient received IV ribavirin. Duration of mechanical ventilation was longer in the treatment group (18.9 +/- 9.5 vs. 14.3 +/- 9.3 days; p = 0.26). No statistically significant differences were observed between groups for any of the secondary end points. CONCLUSIONS: Pediatric patients who received IV palivizumab in addition to standard of care for treatment of RSV infection following initiation of mechanical ventilation experienced similar outcomes to those who received standard of care alone. Further studies are necessary to evaluate the potential benefit of IV palivizumab in addition to current standard of care. PMID- 27199623 TI - Evaluation of Vancomycin Dosing in Pediatric Cystic Fibrosis Patients. AB - OBJECTIVES: The presence of methicillin-resistant Staphylococcus aureus (MRSA) in cystic fibrosis (CF) patients' sputa is associated with a decline in pulmonary function and increased mortality. Vancomycin is the preferred treatment for MRSA pneumonia in children. No published studies have evaluated the vancomycin dose needed to achieve goal vancomycin trough concentrations (VTCs; 15-20 mg/L) in pediatric patients with CF. The primary objective is to determine whether a vancomycin dosage of 60 mg/kg/day achieves a goal VTC in pediatric CF patients. Secondary objectives include determining the average dosage required to reach a goal VTC and the impact of achieving a goal VTC on estimated glomerular filtration rate (eGFR) and pulmonary function. METHODS: A retrospective review of pediatric patients with CF who received vancomycin was conducted. RESULTS: A total of 90 vancomycin treatment courses were analyzed. Standard vancomycin dosing (60 mg/kg/day) achieved goal VTC in 11 courses (12.2%). The mean dosage required to achieve a goal VTC for all courses was 70.6 +/- 16.7 mg/kg/day. Patients who achieved goal VTCs were more often older, weighed more, and had higher serum creatinine concentrations at therapy initiation. On average, a dosage of 70.6 mg/kg/day was required to achieve a goal VTC. Despite dosages up to 120 mg/kg/day, no significant changes in renal function occurred. Achieving a goal VTC had no significant impact on eGFR or pulmonary function during therapy. CONCLUSIONS: Vancomycin dosing of 60 mg/kg/day does not reliably achieve a VTC of 15 to 20 mg/L in pediatric CF patients. Younger CF patients may require higher vancomycin doses. PMID- 27199624 TI - Response of Iron Deficiency Anemia to Intravenous Iron Sucrose in Pediatric Inflammatory Bowel Disease. AB - OBJECTIVES: The objective of this retrospective study was to evaluate the safety and efficacy of intravenous iron sucrose (IS) in iron deficient children with inflammatory bowel disease (IBD) in remission. METHODS: Electronic medical records at a university based pediatric children's hospital were searched for patients in age range 0 to 18 years with diagnosis of IBD and treatment with IS over a 1-year period. Response to IS treatment was assessed by posttreatment changes in ferritin, hemoglobin (Hb), and mean corpuscular volume (MCV). Patients with recorded symptoms of active disease were excluded from analysis of treatment response. RESULTS: Twelve patients were identified by the search criteria, 10 with Crohn's disease (CD), 2 with ulcerative colitis (UC). Data represent 8 patients in remission, 7 with CD and 1 with UC, who received a total of 34 IS infusions. Iron sucrose was administered in cycles of 2 infusions, 2.5 to 3.5 mg/kg/dose (maximum 200 mg), 1 week apart. Mean ferritin increased from 21.4 +/- 9.2 to 52.9 +/- 10.1 ng/mL (p = 0.0005), Hb from 10.9 +/- 0.4 to 11.3 +/- 0.3 g/dL (p = 0.02), and MCV from 76.9 +/- 2 to 79.4 +/- 2 fl (p = 0.006). Iron sucrose treatment normalized ferritin in 6 of 7, Hb in 2 of 8, and MCV in 2 of 5 patients with low pretreatment levels. No adverse effects were recorded. CONCLUSIONS: Two IS infusions of 2.5 to 3.5 mg/kg/dose (maximum 200 mg), given 1 week apart normalized ferritin levels in most pediatric IBD patients in remission without adverse effects. Further studies are needed to determine optimal dosing schedules. PMID- 27199625 TI - Acute Kidney Injury in a Child Receiving Vancomycin and Piperacillin/Tazobactam. AB - Recent reports have described increased risk of acute kidney injury (AKI) in adults receiving concomitant vancomycin and piperacillin/tazobactam, but few reports exist in children. We describe an 8-year-old girl who was admitted to the pediatric intensive care unit with respiratory distress secondary to pneumonia. She began treatment with vancomycin and piperacillin/tazobactam. She developed AKI, and piperacillin/tazobactam and vancomycin were discontinued. Following a furosemide infusion, her AKI resolved and serum creatinine returned to baseline. She later resumed piperacillin/tazobactam monotherapy for multidrug-resistant tracheitis with no evidence of AKI and was eventually discharged to a long-term care facility. The Naranjo probability scale supports a probable drug-related adverse event. Clinicians must be aware of the possibility of AKI with this combination and should monitor renal function and vancomycin concentrations vigilantly. Future prospective studies are needed to explore the incidence and clinical characteristics associated with AKI after this combination in children. PMID- 27199627 TI - Pediatric News. PMID- 27199626 TI - Communication Strategies for Empowering and Protecting Children. AB - Communication with children and adolescents is an area that requires special attention. It is our job as health care professionals to ensure that the information being relayed is provided at a level that can be understood, to ensure patient safety as well as keep a child or adolescent engaged in their own medical care and decision making. This article discusses the importance of communication with children, adolescents, and their caregivers. It focuses on the overall importance of health literacy in communicating health care information to both caregivers and their children. Included are points to consider when communicating at different developmental stages, as well as strategies to help establish rapport. Lastly, the importance of technology and how it can help facilitate communication with this population is introduced. PMID- 27199628 TI - LacaScore: a novel plasma sample quality control tool based on ascorbic acid and lactic acid levels. AB - INTRODUCTION: Metabolome analysis is complicated by the continuous dynamic changes of metabolites in vivo and ex vivo. One of the main challenges in metabolomics is the robustness and reproducibility of results, partially driven by pre-analytical variations. OBJECTIVES: The objective of this study was to analyse the impact of pre-centrifugation time and temperature, and to determine a quality control marker in plasma samples. METHODS: Plasma metabolites were measured by gas chromatography-mass spectrometry (GC-MS) and analysed with the MetaboliteDetector software. The metabolites, which were the most labile to pre analytical variations, were further measured by enzymatic assays. A score was calculated for their use as quality control markers. RESULTS: The pre centrifugation temperature was shown to be critical in the stability of plasma samples and had a significant impact on metabolite concentration profiles. In contrast, pre-centrifugation delay had only a minor impact. Based on the results of this study, whole blood should be kept on wet ice and centrifuged within maximum 3 h as a prerequisite for preparing EDTA plasma samples fit for the purpose of metabolome analysis. CONCLUSIONS: We have established a novel blood sample quality control marker, the LacaScore, based on the ascorbic acid to lactic acid ratio in plasma, which can be used as an indicator of the blood pre centrifugation conditions, and hence the suitability of the sample for metabolome analyses. This method can be applied in research institutes and biobanks, enabling assessment of the quality of their plasma sample collections. PMID- 27199629 TI - Postural Instability in Children with ADHD Is Improved by Methylphenidate. AB - HIGHLIGHTS Both spatial and temporal analyses of the Center of Pressure demonstrate that children with ADHD have poorer postural control than typically developing sex-, age-, and IQ-matched children.Poor sensory integration in postural control could partially explained the deficits in postural stability in children with ADHD.MPH treatment improves postural performance in both spatial and temporal domains in children with ADHD.MPH improves postural control specifically when visual and proprioceptive inputs are misleading.Such improvement could be due to MPH effects on neurons, facilitating cerebellar processing of postural control. The aim of this study was to examine postural control in children with ADHD and explore the effect of methylphenidate (MPH), using spatial and temporal analyses of the center of pressure (CoP). Thirty-eight children with ADHD (mean age 9.82 +/- 0.37 years) and 38 sex- age- and IQ-matched children with typically development were examined. Postural stability was evaluated using the Multitest Equilibre machine (Framiral(r)) at inclusion and after 1 month of MPH in children with ADHD. Postural stability was assessed by recording under several conditions: with eyes open and fixed on a target, with eyes closed and with vision perturbed by optokinetic stimulation, on stable and unstable platforms. At inclusion, we observed poor spatial and temporal postural stability in children with ADHD. The spectral power index was higher in children with ADHD than in controls. Canceling time was shorter at low and medium frequencies of oscillation and longer at higher frequencies in children with ADHD. After 1 month of MPH, the surface area and mean velocity of the CoP decreased significantly under the most complex conditions (unstable platform in the absence of proprioceptive and visual inputs). The spectral power index decreased significantly after MPH while the canceling time did not change. Poor postural control in children with ADHD supports the hypothesis of cerebellar dysfunction in this disorder. Postural control could be improved by a more efficient processing of sensory inputs (a high-level process), as suggested by the decrease in spectral power index after MPH without changes in the canceling time (a low-level process). PMID- 27199630 TI - Single Trial Predictors for Gating Motor-Imagery Brain-Computer Interfaces Based on Sensorimotor Rhythm and Visual Evoked Potentials. AB - For brain-computer interfaces (BCIs) that utilize visual cues to direct the user, the neural signals extracted by the computer are representative of ongoing processes, visual evoked responses, and voluntary modulation. We proposed to use three brain signatures for predicting success on a single trial of a BCI task. The first two features, the amplitude and phase of the pre-trial mu amplitude, were chosen as a correlate for cortical excitability. The remaining feature, related to the visually evoked response to the cue, served as a possible measure of fixation and attention to the task. Of these three features, mu rhythm amplitude over the central electrodes at the time of cue presentation and to a lesser extent the single trial visual evoked response were correlated with the success on the subsequent imagery task. Despite the potential for gating trials using these features, an offline gating simulation was limited in its ability to produce an increase in device throughput. This discrepancy highlights a distinction between the identification of predictive features, and the use of this knowledge in an online BCI. Using such a system, we cannot assume that the user will respond similarly when faced with a scenario where feedback is altered by trials that are gated on a regular basis. The results of this study suggest the possibility of using individualized, pre-task neural signatures for personalized, and asynchronous (self-paced) BCI applications, although these effects need to be quantified in a real-time adaptive scenario in a future study. PMID- 27199631 TI - Human Brain Expansion during Evolution Is Independent of Fire Control and Cooking. AB - What makes humans unique? This question has fascinated scientists and philosophers for centuries and it is still a matter of intense debate. Nowadays, human brain expansion during evolution has been acknowledged to explain our empowered cognitive capabilities. The drivers for such accelerated expansion remain, however, largely unknown. In this sense, studies have suggested that the cooking of food could be a pre-requisite for the expansion of brain size in early hominins. However, this appealing hypothesis is only supported by a mathematical model suggesting that the increasing number of neurons in the brain would constrain body size among primates due to a limited amount of calories obtained from diets. Here, we show, by using a similar mathematical model, that a tradeoff between body mass and the number of brain neurons imposed by dietary constraints during hominin evolution is unlikely. Instead, the predictable number of neurons in the hominin brain varies much more in function of foraging efficiency than body mass. We also review archeological data to show that the expansion of the brain volume in the hominin lineage is described by a linear function independent of evidence of fire control, and therefore, thermal processing of food does not account for this phenomenon. Finally, we report experiments in mice showing that thermal processing of meat does not increase its caloric availability in mice. Altogether, our data indicate that cooking is neither sufficient nor necessary to explain hominin brain expansion. PMID- 27199632 TI - DNA Methylation Profiling at Single-Base Resolution Reveals Gestational Folic Acid Supplementation Influences the Epigenome of Mouse Offspring Cerebellum. AB - It is becoming increasingly more evident that lifestyle, environmental factors, and maternal nutrition during gestation can influence the epigenome of the developing fetus and thus modulate the physiological outcome. Variations in the intake of maternal nutrients affecting one-carbon metabolism may influence brain development and exert long-term effects on the health of the progeny. In this study, we investigated whether supplementation with high maternal folic acid during gestation alters DNA methylation and gene expression in the cerebellum of mouse offspring. We used reduced representation bisulfite sequencing to analyze the DNA methylation profile at the single-base resolution level. The genome-wide DNA methylation analysis revealed that supplementation with higher maternal folic acid resulted in distinct methylation patterns (P < 0.05) of CpG and non-CpG sites in the cerebellum of offspring. Such variations of methylation and gene expression in the cerebellum of offspring were highly sex-specific, including several genes of the neuronal pathways. These findings demonstrate that alterations in the level of maternal folic acid during gestation can influence methylation and gene expression in the cerebellum of offspring. Such changes in the offspring epigenome may alter neurodevelopment and influence the functional outcome of neurologic and psychiatric diseases. PMID- 27199633 TI - TRIO Platform: A Novel Low Profile In vivo Imaging Support and Restraint System for Mice. AB - High resolution, in vivo optical imaging of the mouse brain over time often requires anesthesia, which necessitates maintaining the animal's body temperature and level of anesthesia, as well as securing the head in an optimal, stable position. Controlling each parameter usually requires using multiple systems. Assembling multiple components into the small space on a standard microscope stage can be difficult and some commercially available parts simply do not fit. Furthermore, it is time-consuming to position an animal in the identical position over multiple imaging sessions for longitudinal studies. This is especially true when using an implanted gradient index (GRIN) lens for deep brain imaging. The multiphoton laser beam must be parallel with the shaft of the lens because even a slight tilt of the lens can degrade image quality. In response to these challenges, we have designed a compact, integrated in vivo imaging support system to overcome the problems created by using separate systems during optical imaging in mice. It is a single platform that provides (1) sturdy head fixation, (2) an integrated gas anesthesia mask, and (3) safe warm water heating. This THREE-IN ONE (TRIO) Platform has a small footprint and a low profile that positions a mouse's head only 20 mm above the microscope stage. This height is about one half to one third the height of most commercially available immobilization devices. We have successfully employed this system, using isoflurane in over 40 imaging sessions with an average of 2 h per session with no leaks or other malfunctions. Due to its smaller size, the TRIO Platform can be used with a wider range of upright microscopes and stages. Most of the components were designed in SOLIDWORKS(r) and fabricated using a 3D printer. This additive manufacturing approach also readily permits size modifications for creating systems for other small animals. PMID- 27199636 TI - Editorial: Mechanisms of Neuronal Migration during Corticogenesis. PMID- 27199635 TI - Effects of Amoxicillin and Augmentin on Cystine-Glutamate Exchanger and Glutamate Transporter 1 Isoforms as well as Ethanol Intake in Alcohol-Preferring Rats. AB - Alcohol dependence is associated with alteration of glutamate transport and glutamate neurotransmission. Glutamate transporter 1 (GLT-1) is a major transporter that regulates the majority of extracellular glutamate concentration, which is also regulated by cystine-glutamate exchanger (xCT). Importantly, we recently reported that amoxicillin and Augmentin (amoxicillin/clavulanate) upreglulated GLT-1 expression in nucleus accumbens (NAc) and prefrontal cortex (PFC) as well as reduced ethanol consumption in male P rats. In this study, we examined the effects of amoxicillin and Augmentin on GLT-1 isoforms (GLT-1a and GLT-1b), xCT, and glutamate/aspartate transporter (GLAST) expression in NAc and PFC as well as ethanol intake in male P rats. We found that both compounds significantly reduced ethanol intake, and increased GLT-1a, GLT-1b, and xCT expression in NAc. However, only Augmentin increased GLT-1a, GLT-1b, and xCT expression in PFC. There were no effects of these compounds on GLAST expression in NAc and PFC. These findings demonstrated that Augmentin and amoxicillin have the potential to upregulate GLT-1 isoforms and xCT expression, and consequently attenuate ethanol dependence. PMID- 27199634 TI - The International Deep Brain Stimulation Registry and Database for Gilles de la Tourette Syndrome: How Does It Work? AB - Tourette Syndrome (TS) is a neuropsychiatric disease characterized by a combination of motor and vocal tics. Deep brain stimulation (DBS), already widely utilized for Parkinson's disease and other movement disorders, is an emerging therapy for select and severe cases of TS that are resistant to medication and behavioral therapy. Over the last two decades, DBS has been used experimentally to manage severe TS cases. The results of case reports and small case series have been variable but in general positive. The reported interventions have, however, been variable, and there remain non-standardized selection criteria, various brain targets, differences in hardware, as well as variability in the programming parameters utilized. DBS centers perform only a handful of TS DBS cases each year, making large-scale outcomes difficult to study and to interpret. These limitations, coupled with the variable effect of surgery, and the overall small numbers of TS patients with DBS worldwide, have delayed regulatory agency approval (e.g., FDA and equivalent agencies around the world). The Tourette Association of America, in response to the worldwide need for a more organized and collaborative effort, launched an international TS DBS registry and database. The main goal of the project has been to share data, uncover best practices, improve outcomes, and to provide critical information to regulatory agencies. The international registry and database has improved the communication and collaboration among TS DBS centers worldwide. In this paper we will review some of the key operation details for the international TS DBS database and registry. PMID- 27199639 TI - Evaluation of Event-Based Algorithms for Optical Flow with Ground-Truth from Inertial Measurement Sensor. AB - In this study we compare nine optical flow algorithms that locally measure the flow normal to edges according to accuracy and computation cost. In contrast to conventional, frame-based motion flow algorithms, our open-source implementations compute optical flow based on address-events from a neuromorphic Dynamic Vision Sensor (DVS). For this benchmarking we created a dataset of two synthesized and three real samples recorded from a 240 * 180 pixel Dynamic and Active-pixel Vision Sensor (DAVIS). This dataset contains events from the DVS as well as conventional frames to support testing state-of-the-art frame-based methods. We introduce a new source for the ground truth: In the special case that the perceived motion stems solely from a rotation of the vision sensor around its three camera axes, the true optical flow can be estimated using gyro data from the inertial measurement unit integrated with the DAVIS camera. This provides a ground-truth to which we can compare algorithms that measure optical flow by means of motion cues. An analysis of error sources led to the use of a refractory period, more accurate numerical derivatives and a Savitzky-Golay filter to achieve significant improvements in accuracy. Our pure Java implementations of two recently published algorithms reduce computational cost by up to 29% compared to the original implementations. Two of the algorithms introduced in this paper further speed up processing by a factor of 10 compared with the original implementations, at equal or better accuracy. On a desktop PC, they run in real time on dense natural input recorded by a DAVIS camera. PMID- 27199638 TI - Decoding of Covert Vowel Articulation Using Electroencephalography Cortical Currents. AB - With the goal of providing assistive technology for the communication impaired, we proposed electroencephalography (EEG) cortical currents as a new approach for EEG-based brain-computer interface spellers. EEG cortical currents were estimated with a variational Bayesian method that uses functional magnetic resonance imaging (fMRI) data as a hierarchical prior. EEG and fMRI data were recorded from ten healthy participants during covert articulation of Japanese vowels /a/ and /i/, as well as during a no-imagery control task. Applying a sparse logistic regression (SLR) method to classify the three tasks, mean classification accuracy using EEG cortical currents was significantly higher than that using EEG sensor signals and was also comparable to accuracies in previous studies using electrocorticography. SLR weight analysis revealed vertices of EEG cortical currents that were highly contributive to classification for each participant, and the vertices showed discriminative time series signals according to the three tasks. Furthermore, functional connectivity analysis focusing on the highly contributive vertices revealed positive and negative correlations among areas related to speech processing. As the same findings were not observed using EEG sensor signals, our results demonstrate the potential utility of EEG cortical currents not only for engineering purposes such as brain-computer interfaces but also for neuroscientific purposes such as the identification of neural signaling related to language processing. PMID- 27199637 TI - Deep Brain Stimulation: A Paradigm Shifting Approach to Treat Parkinson's Disease. AB - Parkinson disease (PD) is a chronic and progressive movement disorder classically characterized by slowed voluntary movements, resting tremor, muscle rigidity, and impaired gait and balance. Medical treatment is highly successful early on, though the majority of people experience significant complications in later stages. In advanced PD, when medications no longer adequately control motor symptoms, deep brain stimulation (DBS) offers a powerful therapeutic alternative. DBS involves the surgical implantation of one or more electrodes into specific areas of the brain, which modulate or disrupt abnormal patterns of neural signaling within the targeted region. Outcomes are often dramatic following DBS, with improvements in motor function and reductions motor complications having been repeatedly demonstrated. Given such robust responses, emerging indications for DBS are being investigated. In parallel with expansions of therapeutic scope, advancements within the areas of neurosurgical technique and the precision of stimulation delivery have recently broadened as well. This review focuses on the revolutionary addition of DBS to the therapeutic armamentarium for PD, and summarizes the technological advancements in the areas of neuroimaging and biomedical engineering intended to improve targeting, programming, and overall management. PMID- 27199640 TI - One for All? Hitting Multiple Alzheimer's Disease Targets with One Drug. AB - HIGHLIGHTS Many AD target combinations are being explored for multi-target drug design.New databases and models increase the potential of computational drug designLiraglutide and other antidiabetics are strong candidates for repurposing to AD.Donecopride a dual 5-HT/AChE inhibitor shows promise in pre-clinical studies Alzheimer's Disease is a complex and multifactorial disease for which the mechanism is still not fully understood. As new insights into disease progression are discovered, new drugs must be designed to target those aspects of the disease that cause neuronal damage rather than just the symptoms currently addressed by single target drugs. It is becoming possible to target several aspects of the disease pathology at once using multi-target drugs (MTDs). Intended as an introduction for non-experts, this review describes the key MTD design approaches, namely structure-based, in silico, and data-mining, to evaluate what is preventing compounds progressing through the clinic to the market. Repurposing current drugs using their off-target effects reduces the cost of development, time to launch, and the uncertainty associated with safety and pharmacokinetics. The most promising drugs currently being investigated for repurposing to Alzheimer's Disease are rasagiline, originally developed for the treatment of Parkinson's Disease, and liraglutide, an antidiabetic. Rational drug design can combine pharmacophores of multiple drugs, systematically change functional groups, and rank them by virtual screening. Hits confirmed experimentally are rationally modified to generate an effective multi-potent lead compound. Examples from this approach are ASS234 with properties similar to rasagiline, and donecopride, a hybrid of an acetylcholinesterase inhibitor and a 5-HT4 receptor agonist with pro-cognitive effects. Exploiting these interdisciplinary approaches, public-private collaborative lead factories promise faster delivery of new drugs to the clinic. PMID- 27199642 TI - Clarifying CLARITY: Quantitative Optimization of the Diffusion Based Delipidation Protocol for Genetically Labeled Tissue. AB - Tissue clarification has been recently proposed to allow deep tissue imaging without light scattering. The clarification parameters are somewhat arbitrary and dependent on tissue type, source and dimension: every laboratory has its own protocol, but a quantitative approach to determine the optimum clearing time is still lacking. Since the use of transgenic mouse lines that express fluorescent proteins to visualize specific cell populations is widespread, a quantitative approach to determine the optimum clearing time for genetically labeled neurons from thick murine brain slices using CLARITY2 is described. In particular, as the main objective of the delipidation treatment is to clarify tissues, while limiting loss of fluorescent signal, the "goodness" of clarification was evaluated by considering the bulk tissue clarification index (BTCi) and the fraction of the fluorescent marker retained in the slice as easily quantifiable macroscale parameters. Here we describe the approach, illustrating an example of how it can be used to determine the optimum clearing time for 1 mm-thick cerebellar slice from transgenic L7GFP mice, in which Purkinje neurons express the GFP (green fluorescent protein) tag. To validate the method, we evaluated confocal stacks of our samples using standard image processing indices (i.e., the mean pixel intensity of neurons and the contrast-to-noise ratio) as figures of merit for image quality. The results show that detergent-based delipidation for more than 5 days does not increase tissue clarity but the fraction of GFP in the tissue continues to diminish. The optimum clearing time for 1 mm-thick slices was thus identified as 5 days, which is the best compromise between the increase in light penetration depth due to removal of lipids and a decrease in fluorescent signal as a consequence of protein loss: further clearing does not improve tissue transparency, but only leads to more protein removal or degradation. The rigorous quantitative approach described can be generalized to any clarification method to identify the moment when the clearing process should be terminated to avoid useless protein loss. PMID- 27199641 TI - Alzheimer's Disease and Hippocampal Adult Neurogenesis; Exploring Shared Mechanisms. AB - New neurons incorporate into the granular cell layer of the dentate gyrus throughout life. Neurogenesis is modulated by behavior and plays a major role in hippocampal plasticity. Along with older mature neurons, new neurons structure the dentate gyrus, and determine its function. Recent data suggest that the level of hippocampal neurogenesis is substantial in the human brain, suggesting that neurogenesis may have important implications for human cognition. In support of that, impaired neurogenesis compromises hippocampal function and plays a role in cognitive deficits in Alzheimer's disease mouse models. We review current work suggesting that neuronal differentiation is defective in Alzheimer's disease, leading to dysfunction of the dentate gyrus. Additionally, alterations in critical signals regulating neurogenesis, such as presenilin-1, Notch 1, soluble amyloid precursor protein, CREB, and beta-catenin underlie dysfunctional neurogenesis in Alzheimer's disease. Lastly, we discuss the detectability of neurogenesis in the live mouse and human brain, as well as the therapeutic implications of enhancing neurogenesis for the treatment of cognitive deficits and Alzheimer's disease. PMID- 27199643 TI - Signal Fluctuation Sensitivity: An Improved Metric for Optimizing Detection of Resting-State fMRI Networks. AB - Task-free connectivity analyses have emerged as a powerful tool in functional neuroimaging. Because the cross-correlations that underlie connectivity measures are sensitive to distortion of time-series, here we used a novel dynamic phantom to provide a ground truth for dynamic fidelity between blood oxygen level dependent (BOLD)-like inputs and fMRI outputs. We found that the de facto quality metric for task-free fMRI, temporal signal to noise ratio (tSNR), correlated inversely with dynamic fidelity; thus, studies optimized for tSNR actually produced time-series that showed the greatest distortion of signal dynamics. Instead, the phantom showed that dynamic fidelity is reasonably approximated by a measure that, unlike tSNR, dissociates signal dynamics from scanner artifact. We then tested this measure, signal fluctuation sensitivity (SFS), against human resting-state data. As predicted by the phantom, SFS-and not tSNR-is associated with enhanced sensitivity to both local and long-range connectivity within the brain's default mode network. PMID- 27199644 TI - Editorial: Essential Pathways and Circuits of Autism Pathogenesis. PMID- 27199646 TI - Skimming Digits: Neuromorphic Classification of Spike-Encoded Images. AB - The growing demands placed upon the field of computer vision have renewed the focus on alternative visual scene representations and processing paradigms. Silicon retinea provide an alternative means of imaging the visual environment, and produce frame-free spatio-temporal data. This paper presents an investigation into event-based digit classification using N-MNIST, a neuromorphic dataset created with a silicon retina, and the Synaptic Kernel Inverse Method (SKIM), a learning method based on principles of dendritic computation. As this work represents the first large-scale and multi-class classification task performed using the SKIM network, it explores different training patterns and output determination methods necessary to extend the original SKIM method to support multi-class problems. Making use of SKIM networks applied to real-world datasets, implementing the largest hidden layer sizes and simultaneously training the largest number of output neurons, the classification system achieved a best-case accuracy of 92.87% for a network containing 10,000 hidden layer neurons. These results represent the highest accuracies achieved against the dataset to date and serve to validate the application of the SKIM method to event-based visual classification tasks. Additionally, the study found that using a square pulse as the supervisory training signal produced the highest accuracy for most output determination methods, but the results also demonstrate that an exponential pattern is better suited to hardware implementations as it makes use of the simplest output determination method based on the maximum value. PMID- 27199645 TI - Representation of Instantaneous and Short-Term Loudness in the Human Cortex. AB - Acoustic signals pass through numerous transforms in the auditory system before perceptual attributes such as loudness and pitch are derived. However, relatively little is known as to exactly when these transformations happen, and where, cortically or sub-cortically, they occur. In an effort to examine this, we investigated the latencies and locations of cortical entrainment to two transforms predicted by a model of loudness perception for time-varying sounds: the transforms were instantaneous loudness and short-term loudness, where the latter is hypothesized to be derived from the former and therefore should occur later in time. Entrainment of cortical activity was estimated from electro- and magneto-encephalographic (EMEG) activity, recorded while healthy subjects listened to continuous speech. There was entrainment to instantaneous loudness bilaterally at 45, 100, and 165 ms, in Heschl's gyrus, dorsal lateral sulcus, and Heschl's gyrus, respectively. Entrainment to short-term loudness was found in both the dorsal lateral sulcus and superior temporal sulcus at 275 ms. These results suggest that short-term loudness is derived from instantaneous loudness, and that this derivation occurs after processing in sub-cortical structures. PMID- 27199647 TI - Editorial: Neural Signal Estimation in the Human Brain. PMID- 27199648 TI - Predictive Technologies: Can Smart Tools Augment the Brain's Predictive Abilities? AB - The ability of "looking into the future"-namely, the capacity of anticipating future states of the environment or of the body-represents a fundamental function of human (and animal) brains. A goalkeeper who tries to guess the ball's direction; a chess player who attempts to anticipate the opponent's next move; or a man-in-love who tries to calculate what are the chances of her saying yes-in all these cases, people are simulating possible future states of the world, in order to maximize the success of their decisions or actions. Research in neuroscience is showing that our ability to predict the behavior of physical or social phenomena is largely dependent on the brain's ability to integrate current and past information to generate (probabilistic) simulations of the future. But could predictive processing be augmented using advanced technologies? In this contribution, we discuss how computational technologies may be used to support, facilitate or enhance the prediction of future events, by considering exemplificative scenarios across different domains, from simpler sensorimotor decisions to more complex cognitive tasks. We also examine the key scientific and technical challenges that must be faced to turn this vision into reality. PMID- 27199649 TI - Metabolic Covariant Network in Relation to Nigrostriatal Degeneration in Carbon Monoxide Intoxication-Related Parkinsonism. AB - Presence of parkinsonian features after carbon monoxide (CO) intoxication is well known and the severity was found to relate to the pre-synaptic dopaminergic deficits. There is no systemic study to analyse the functional network involved in CO-related Parkinsonism. Forty-five CO-related parkinsonism patients and 25 aged-matched controls completed the 3D T1-weighted imaging and (18)F-fluoro-2 deoxyglucose positron emission tomography (FDG-PET). Voxel-based morphometry (VBM) was performed to assess the structural and functional brain differences between the patients and controls. Spatial covariant networks responsible for distinguishing patients and controls were constructed using independent component analysis. For validation, the pre-synaptic dopaminergic functional network was established by regression model using striatal TRODAT-1 SPECT as the independent variable. The clinical significance of both networks was determined by correlation with the Unified Parkinson's Disease Rating Scale (UPDRS). Compared with controls, the spatial covariant signals of FDG-PET were significantly lower in the medial and lateral frontal, caudate nucleus, dorsomedial prefrontal areas, and temporal-parietal regions while the spatial intensities correlated significantly with UPDRS total scores. The functional network that correlated with striatum pre-synaptic dopaminergic uptakes included the midbrain, thalamus, caudate, lateral frontal cortex, ventral striatum, ventral, or dorsal anterior cingulate cortex. Both networks overlapped considerably and the topographies reflected structural damage pattern. Our study provides evidence that glucose metabolism in CO-parkinsonism patients pertains to an organized covariant pattern in the cortical regions that is spatially coherent with the cortical map of pre synaptic dopamine deficits. As the fronto-temporal, striatum, and temporal parietal areas were involved, the unique metabolic covariant network suggests a different pathophysiology in CO-related parkinsonism. PMID- 27199650 TI - Cerebellar Functional Parcellation Using Sparse Dictionary Learning Clustering. AB - The human cerebellum has recently been discovered to contribute to cognition and emotion beyond the planning and execution of movement, suggesting its functional heterogeneity. We aimed to identify the functional parcellation of the cerebellum using information from resting-state functional magnetic resonance imaging (rs fMRI). For this, we introduced a new data-driven decomposition-based functional parcellation algorithm, called Sparse Dictionary Learning Clustering (SDLC). SDLC integrates dictionary learning, sparse representation of rs-fMRI, and k-means clustering into one optimization problem. The dictionary is comprised of an over complete set of time course signals, with which a sparse representation of rs fMRI signals can be constructed. Cerebellar functional regions were then identified using k-means clustering based on the sparse representation of rs-fMRI signals. We solved SDLC using a multi-block hybrid proximal alternating method that guarantees strong convergence. We evaluated the reliability of SDLC and benchmarked its classification accuracy against other clustering techniques using simulated data. We then demonstrated that SDLC can identify biologically reasonable functional regions of the cerebellum as estimated by their cerebello cortical functional connectivity. We further provided new insights into the cerebello-cortical functional organization in children. PMID- 27199651 TI - Adult Born Olfactory Bulb Dopaminergic Interneurons: Molecular Determinants and Experience-Dependent Plasticity. AB - The olfactory bulb (OB) is a highly plastic brain region involved in the early processing of olfactory information. A remarkably feature of the OB circuits in rodents is the constitutive integration of new neurons that takes place during adulthood. Newborn cells in the adult OB are mostly inhibitory interneurons belonging to chemically, morphologically and functionally heterogeneous types. Although there is general agreement that adult neurogenesis in the OB plays a key role in sensory information processing and olfaction-related plasticity, the contribution of each interneuron subtype to such functions is far to be elucidated. Here, we focus on the dopaminergic (DA) interneurons: we highlight recent findings about their morphological features and then describe the molecular factors required for the specification/differentiation and maintenance of the DA phenotype in adult born neurons. We also discuss dynamic changes of the DA interneuron population related to age, environmental stimuli and lesions, and their possible functional implications. PMID- 27199652 TI - Neural Decoding and "Inner" Psychophysics: A Distance-to-Bound Approach for Linking Mind, Brain, and Behavior. AB - A fundamental challenge for cognitive neuroscience is characterizing how the primitives of psychological theory are neurally implemented. Attempts to meet this challenge are a manifestation of what Fechner called "inner" psychophysics: the theory of the precise mapping between mental quantities and the brain. In his own time, inner psychophysics remained an unrealized ambition for Fechner. We suggest that, today, multivariate pattern analysis (MVPA), or neural "decoding," methods provide a promising starting point for developing an inner psychophysics. A cornerstone of these methods are simple linear classifiers applied to neural activity in high-dimensional activation spaces. We describe an approach to inner psychophysics based on the shared architecture of linear classifiers and observers under decision boundary models such as signal detection theory. Under this approach, distance from a decision boundary through activation space, as estimated by linear classifiers, can be used to predict reaction time in accordance with signal detection theory, and distance-to-bound models of reaction time. Our "neural distance-to-bound" approach is potentially quite general, and simple to implement. Furthermore, our recent work on visual object recognition suggests it is empirically viable. We believe the approach constitutes an important step along the path to an inner psychophysics that links mind, brain, and behavior. PMID- 27199653 TI - Abnormalities of Inter- and Intra-Hemispheric Functional Connectivity in Autism Spectrum Disorders: A Study Using the Autism Brain Imaging Data Exchange Database. AB - Recently, the Autism Brain Imaging Data Exchange (ABIDE) project revealed decreased functional connectivity in individuals with Autism Spectrum Disorders (ASD) relative to the typically developing controls (TDCs). However, it is still questionable whether the source of functional under-connectivity in subjects with ASD is equally contributed by the ipsilateral and contralateral parts of the brain. In this study, we decomposed the inter- and intra-hemispheric regions and compared the functional connectivity density (FCD) between 458 subjects with ASD and 517 TDCs from the ABIDE database. We quantified the inter- and intra hemispheric FCDs in the brain by counting the number of functional connectivity with all voxels in the opposite and same hemispheric brain regions, respectively. Relative to TDCs, both inter- and intra-hemispheric FCDs in the posterior cingulate cortex, lingual/parahippocampal gyrus, and postcentral gyrus were significantly decreased in subjects with ASD. Moreover, in the ASD group, the restricted and repetitive behavior subscore of the Autism Diagnostic Observation Schedule (ADOS-RRB) score showed significant negative correlations with the average inter-hemispheric FCD and contralateral FCD in the lingual/parahippocampal gyrus cluster. Also, the ADOS-RRB score showed significant negative correlations with the average contralateral FCD in the default mode network regions such as the posterior cingulate cortex and precuneus. Taken together, our findings imply that a deficit of non-social functioning processing in ASD such as restricted and repetitive behaviors and sensory hypersensitivity could be determined via both inter- and intra hemispheric functional disconnections. PMID- 27199654 TI - Intrahippocampal Administration of Ibotenic Acid Induced Cholinergic Dysfunction via NR2A/NR2B Expression: Implications of Resveratrol against Alzheimer Disease Pathophysiology. AB - Although several drugs revealed moderate amelioration of symptoms, none of them have sufficient potency to prevent or reverse the progression toward Alzheimer's disease (AD) pathology. Resveratrol (RSV), a polyphenolic compound has shown an outstanding therapeutic effect on a broad spectrum of diseases like age associated neurodegeneration, inflammation etc. The present study was thus conducted to assess the therapeutic efficacy of RSV in ameliorating the deleterious effects of Ibotenic acid (IBO) in male Wistar rats. Stereotactic intrahippocampal administration of IBO (5 MUg/MUl) lesioned rats impairs cholinergic transmission, learning and memory performance that is rather related to AD and thus chosen as a suitable model to understand the drug efficacy in preventing AD pathophysiology. Since IBO is an agonist of glutamate, it is expected to exhibit an excitotoxic effect by altering glutamatergic receptors like NMDA receptor. The current study displayed significant alterations in the mRNA expression of NR2A and NR2B subunits of NMDA receptors, and further it is surprising to note that cholinergic receptors decreased in expression particularly alpha7-nAChR with increased m1AChR. RSV administration (20 mg/kg body weight, i.p.) significantly reduced these changes in IBO induced rats. Glutamatergic and cholinergic receptor alterations were associated with significant changes in the behavioral parameters of rats induced by IBO. While RSV improved spatial learning performance, attenuated immobility, and improvised open field activity in IBO induced rats. NR2B activation in the present study might mediate cell death through oxidative stress that form the basis of abnormal behavioral pattern in IBO induced rats. Interestingly, RSV that could efficiently encounter oxidative stress have significantly decreased stress markers viz., nitrite, PCO, and MDA levels by enhancing antioxidant status. Histopathological analysis displayed significant reduction in the hippocampal pyramidal layer thickness and live neurons in IBO induced rats, with slight pathological changes in the entorhinal cortex (EC) of rat brain, which was prevented on RSV administration. Our study thus concludes that RSV administration significantly ameliorated the deleterious effects in the IBO lesioned rat model for AD by alleviating cholinergic pathways, reducing oxidative stress and thereby improving spatial memory. PMID- 27199655 TI - CRISPR/Cas9: Implications for Modeling and Therapy of Neurodegenerative Diseases. AB - CRISPR/Cas9 is now used widely to genetically modify the genomes of various species. The ability of CRISPR/Cas9 to delete DNA sequences and correct DNA mutations opens up a new avenue to treat genetic diseases that are caused by DNA mutations. In this review, we describe the advantages of using CRISPR/Cas9 to engineer genomic DNAs in animal embryos, as well as in specific regions or cell types in the brain. We also discuss how to apply CRISPR/Cas9 to establish animal models of neurodegenerative diseases, such as Parkinson's and Huntington's disease (HD), and to treat these disorders that are caused by genetic mutations. PMID- 27199656 TI - Reduced miR-659-3p Levels Correlate with Progranulin Increase in Hypoxic Conditions: Implications for Frontotemporal Dementia. AB - Progranulin (PGRN) is a secreted protein expressed ubiquitously throughout the body, including the brain, where it localizes in neurons and is activated microglia. Loss-of-function mutations in the GRN gene are an important cause of familial frontotemporal lobar degeneration (FTLD). PGRN has a neurotrophic and anti-inflammatory activity, and it is neuroprotective in several injury conditions, such as oxygen or glucose deprivation, oxidative injury, and hypoxic stress. Indeed, we have previously demonstrated that hypoxia induces the up regulation of GRN transcripts. Several studies have shown microRNAs (miRNAs) involvement in hypoxia. Moreover, in FTLD patients with a genetic variant of GRN (rs5848), the reinforcement of miR-659-3p binding site has been suggested to be a risk factor. Here, we report that miR-659-3p interacts directly with GRN 3'UTR as shown by luciferase assay in HeLa cells and ELISA and Western Blot analysis in HeLa and Kelly cells. Moreover, we demonstrate the physical binding between GRN mRNA and miR-659-3p employing a miRNA capture-affinity technology in SK-N-BE and Kelly cells. In order to study miRNAs involvement in hypoxia-mediated up regulation of GRN, we evaluated miR-659-3p levels in SK-N-BE cells after 24 h of hypoxic treatment, finding them inversely correlated to GRN transcripts. Furthermore, we analyzed an animal model of asphyxia, finding that GRN mRNA levels increased at post-natal day (pnd) 1 and pnd 4 in rat cortices subjected to asphyxia in comparison to control rats and miR-659-3p decreased at pnd 4 just when GRN reached the highest levels. Our results demonstrate the interaction between miR-659-3p and GRN transcript and the involvement of miR-659-3p in GRN up regulation mediated by hypoxic/ischemic insults. PMID- 27199657 TI - Retinal Remodeling and Metabolic Alterations in Human AMD. AB - Age-related macular degeneration (AMD) is a progressive retinal degeneration resulting in central visual field loss, ultimately causing debilitating blindness. AMD affects 18% of Americans from 65 to 74, 30% older than 74 years of age and is the leading cause of severe vision loss and blindness in Western populations. While many genetic and environmental risk factors are known for AMD, we currently know less about the mechanisms mediating disease progression. The pathways and mechanisms through which genetic and non-genetic risk factors modulate development of AMD pathogenesis remain largely unexplored. Moreover, current treatment for AMD is palliative and limited to wet/exudative forms. Retina is a complex, heterocellular tissue and most retinal cell classes are impacted or altered in AMD. Defining disease and stage-specific cytoarchitectural and metabolic responses in AMD is critical for highlighting targets for intervention. The goal of this article is to illustrate cell types impacted in AMD and demonstrate the implications of those changes, likely beginning in the retinal pigment epithelium (RPE), for remodeling of the the neural retina. Tracking heterocellular responses in disease progression is best achieved with computational molecular phenotyping (CMP), a tool that enables acquisition of a small molecule fingerprint for every cell in the retina. CMP uncovered critical cellular and molecular pathologies (remodeling and reprogramming) in progressive retinal degenerations such as retinitis pigmentosa (RP). We now applied these approaches to normal human and AMD tissues mapping progression of cellular and molecular changes in AMD retinas, including late-stage forms of the disease. PMID- 27199658 TI - Effects of Transforming Growth Factor Beta 1 in Cerebellar Development: Role in Synapse Formation. AB - Granule cells (GC) are the most numerous glutamatergic neurons in the cerebellar cortex and represent almost half of the neurons of the central nervous system. Despite recent advances, the mechanisms of how the glutamatergic synapses are formed in the cerebellum remain unclear. Among the TGF-beta family, TGF-beta 1 (TGF-beta1) has been described as a synaptogenic molecule in invertebrates and in the vertebrate peripheral nervous system. A recent paper from our group demonstrated that TGF-beta1 increases the excitatory synapse formation in cortical neurons. Here, we investigated the role of TGF-beta1 in glutamatergic cerebellar neurons. We showed that the expression profile of TGF-beta1 and its receptor, TbetaRII, in the cerebellum is consistent with a role in synapse formation in vitro and in vivo. It is low in the early postnatal days (P1-P9), increases after postnatal day 12 (P12), and remains high until adulthood (P30). We also found that granule neurons express the TGF-beta receptor mRNA and protein, suggesting that they may be responsive to the synaptogenic effect of TGF beta1. Treatment of granular cell cultures with TGF-beta1 increased the number of glutamatergic excitatory synapses by 100%, as shown by immunocytochemistry assays for presynaptic (synaptophysin) and post-synaptic (PSD-95) proteins. This effect was dependent on TbetaRI activation because addition of a pharmacological inhibitor of TGF-beta, SB-431542, impaired the formation of synapses between granular neurons. Together, these findings suggest that TGF-beta1 has a specific key function in the cerebellum through regulation of excitatory synapse formation between granule neurons. PMID- 27199659 TI - Surgery-Induced Hippocampal Angiotensin II Elevation Causes Blood-Brain Barrier Disruption via MMP/TIMP in Aged Rats. AB - Reversible blood-brain barrier (BBB) disruption has been uniformly reported in several animal models of postoperative cognitive dysfunction (POCD). Nevertheless, the precise mechanism underlying this occurrence remains unclear. Using an aged rat model of POCD, we investigated the dynamic changes in expression of molecules involved in BBB disintegration, matrix metalloproteinase 2 (MMP-2) and -9 (MMP-9), as well as three of their endogenous tissue inhibitors of MMP (TIMP-1, -2, -3), and tried to establish the correlation between MMP/TIMP balance and surgery-induced hippocampal BBB disruption. We validated the increased hippocampal expression of angiotensin II (Ang II) and Ang II receptor type 1 (AT1) after surgery. We also found MMP/TIMP imbalance as early as 6 h after surgery, together with increased BBB permeability and decreased expression of Occludin and zonula occludens-1 (ZO-1), as well as increased basal lamina protein laminin at 24 h postsurgery. The AT1 antagonist candesartan restored MMP/TIMP equilibrium and modulated expression of Occludin and laminin, but not ZO 1, thereby improving BBB permeability. These events were accompanied by suppression of the surgery-induced canonical nuclear factor-kappaB (NF-kappaB) activation cascade. Nevertheless, AT1 antagonism did not affect nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARgamma) expression. Collectively, these findings suggest that surgery-induced Ang II release impairs BBB integrity by activating NF-kappaB signaling and disrupting downstream MMP/TIMP balance via AT1 receptor. PMID- 27199661 TI - Erratum: An Optimized Approach to Recover Secreted Proteins from Fibroblast Conditioned-Media for Secretomic Analysis. AB - [This corrects the article on p. 70 in vol. 10, PMID: 27064649.]. PMID- 27199660 TI - Selective Localization of Shanks to VGLUT1-Positive Excitatory Synapses in the Mouse Hippocampus. AB - Members of the Shank family of multidomain proteins (Shank1, Shank2, and Shank3) are core components of the postsynaptic density (PSD) of excitatory synapses. At synaptic sites Shanks serve as scaffolding molecules that cluster neurotransmitter receptors as well as cell adhesion molecules attaching them to the actin cytoskeleton. In this study we investigated the synapse specific localization of Shank1-3 and focused on well-defined synaptic contacts within the hippocampal formation. We found that all three family members are present only at VGLUT1-positive synapses, which is particularly visible at mossy fiber contacts. No costaining was found at VGLUT2-positive contacts indicating that the molecular organization of VGLUT2-associated PSDs diverges from classical VGLUT1-positive excitatory contacts in the hippocampus. In light of SHANK mutations in neuropsychiatric disorders, this study indicates which glutamatergic networks within the hippocampus will be primarily affected by shankopathies. PMID- 27199662 TI - Local Optogenetic Induction of Fast (20-40 Hz) Pyramidal-Interneuron Network Oscillations in the In Vitro and In Vivo CA1 Hippocampus: Modulation by CRF and Enforcement of Perirhinal Theta Activity. AB - The neurophysiological processes that can cause theta-to-gamma frequency range (4 80 Hz) network oscillations in the rhinal cortical-hippocampal system and the potential connectivity-based interactions of such forebrain rhythms are a topic of intensive investigation. Here, using selective Channelrhodopsin-2 (ChR2) expression in mouse forebrain glutamatergic cells, we were able to locally, temporally precisely, and reliably induce fast (20-40 Hz) field potential oscillations in hippocampal area CA1 in vitro (at 25 degrees C) and in vivo (i.e., slightly anesthetized NEX-Cre-ChR2 mice). As revealed by pharmacological analyses and patch-clamp recordings from pyramidal cells and GABAergic interneurons in vitro, these light-triggered oscillations can exclusively arise from sustained suprathreshold depolarization (~200 ms or longer) and feedback inhibition of CA1 pyramidal neurons, as being mandatory for prototypic pyramidal interneuron network (P-I) oscillations. Consistently, the oscillations comprised rhythmically occurring population spikes (generated by pyramidal cells) and their frequency increased with increasing spectral power. We further demonstrate that the optogenetically driven CA1 oscillations, which remain stable over repeated evocations, are impaired by the stress hormone corticotropin-releasing factor (CRF, 125 nM) in vitro and, even more remarkably, found that they are accompanied by concurrent states of enforced theta activity in the memory-associated perirhinal cortex (PrC) in vivo. The latter phenomenon most likely derives from neurotransmission via a known, but poorly studied excitatory CA1->PrC pathway. Collectively, our data provide evidence for the existence of a prototypic (CRF sensitive) P-I gamma rhythm generator in area CA1 and suggest that CA1 P-I oscillations can rapidly up-regulate theta activity strength in hippocampus innervated rhinal networks, at least in the PrC. PMID- 27199664 TI - Effects of Pin1 Loss in Hdh(Q111) Knock-in Mice. AB - Huntington's disease (HD) is a fatal, dominantly inherited, neurodegenerative disorder due to a pathological expansion of the CAG repeat in the coding region of the HTT gene. In the quest for understanding the molecular basis of neurodegeneration, we have previously demonstrated that the prolyl isomerase Pin1 plays a crucial role in mediating p53-dependent apoptosis triggered by mutant huntingtin (mHtt) in vitro. To assess the effects of the lack of Pin1 in vivo, we have bred Pin1 knock-out mice with Hdh(Q111) knock-in mice, a genetically precise model of HD. We show that Pin1 genetic ablation modifies a portion of Hdh(Q111) phenotypes in a time-dependent fashion. As an early event, Pin1 activity reduces the DNA damage response (DDR). In midlife mice, by taking advantage of next generation sequencing technology, we show that Pin1 activity modulates a portion of the alterations triggered by mHtt, extending the role of Pin1 to two additional Hdh(Q111) phenotypes: the unbalance in the "synthesis/concentration of hormones", as well as the alteration of "Wnt/beta-catenin signaling". In aging animals, Pin1 significantly increases the number of mHtt-positive nuclear inclusions while it reduces gliosis. In summary, this work provides further support for a role of Pin1 in HD pathogenesis. PMID- 27199665 TI - Mutual Control of Cholinergic and Low-Threshold Spike Interneurons in the Striatum. AB - The striatum is the largest nucleus of the basal ganglia and is crucially involved in action selection and reward processing. Cortical and thalamic inputs to the striatum are processed by local networks in which several classes of interneurons play an important, but still poorly understood role. Here we investigated the interactions between cholinergic and low-threshold spike (LTS) interneurons. LTS interneurons were hyperpolarized by co-application of muscarinic and nicotinic receptor antagonists (atropine and mecamylamine, respectively). Mecamylamine alone also caused hyperpolarizations, while atropine alone caused depolarizations and increased firing. LTS interneurons were also under control of tonic GABA, as application of the GABAA receptor antagonist picrotoxin caused depolarizations and increased firing. Frequency of spontaneous GABAergic events in LTS interneurons was increased by co-application of atropine and mecamylamine or by atropine alone, but reduced by mecamylamine alone. In the presence of picrotoxin and tetrodotoxin (TTX), atropine and mecamylamine depolarized the LTS interneurons. We concluded that part of the excitatory effects of tonic acetylcholine (ACh) on LTS interneurons were due to cholinergic modulation of tonic GABA. We then studied the influence of LTS interneurons on cholinergic interneurons. Application of antagonists of somatostatin or neuropeptide Y (NPY) receptors or of an inhibitor of nitric oxide synthase (L NAME) did not cause detectable effects in cholinergic interneurons. However, prolonged synchronized depolarizations of LTS interneurons (elicited with optogenetics tools) caused slow-onset depolarizations in cholinergic interneurons, which were often accompanied by strong action potential firing and were fully abolished by L-NAME. Thus, a mutual excitatory influence exists between LTS and cholinergic interneurons in the striatum, providing an opportunity for sustained activation of the two cell types. This activation may endow the striatal microcircuits with the ability to enter a high ACh/high nitric oxide regime when adequately triggered by external excitatory stimuli to these interneurons. PMID- 27199666 TI - Corrigendum: Platelet Activating Factor Enhances Synaptic Vesicle Exocytosis Via PKC, Elevated Intracellular Calcium, and Modulation of Synapsin 1 Dynamics and Phosphorylation. AB - [This corrects the article on p. 505 in vol. 9, PMID: 26778968.]. PMID- 27199663 TI - Extracellular Vesicles in Physiology, Pathology, and Therapy of the Immune and Central Nervous System, with Focus on Extracellular Vesicles Derived from Mesenchymal Stem Cells as Therapeutic Tools. AB - Extracellular vesicles (EVs) are membrane-surrounded structures released by most cell types. They are characterized by a specific set of proteins, lipids and nucleic acids. EVs have been recognized as potent vehicles of intercellular communication to transmit biological signals between cells. In addition, pathophysiological roles of EVs in conditions like cancer, infectious diseases and neurodegenerative disorders are well established. In recent years focus has been shifted on therapeutic use of stem cell derived-EVs. Use of stem cell derived-EVs present distinct advantage over the whole stem cells as EVs do not replicate and after intravenous administration, they are less likely to trap inside the lungs. From the therapeutic perspective, the most promising cellular sources of EVs are mesenchymal stem cells (MSCs), which are easy to obtain and maintain. Therapeutic activity of MSCs has been shown in numerous animal models and the beneficial paracrine effect of MSCs may be mediated by EVs. The various components of MSC derived-EVs such as proteins, lipids, and RNA might play a specific therapeutic role. In this review, we characterize the role of EVs in immune and central nervous system (CNS); present evidences for defective signaling of these vesicles in neurodegeneration and therapeutic role of EVs in CNS. PMID- 27199668 TI - Mediation of Autophagic Cell Death by Type 3 Ryanodine Receptor (RyR3) in Adult Hippocampal Neural Stem Cells. AB - Cytoplasmic Ca(2+) actively engages in diverse intracellular processes from protein synthesis, folding and trafficking to cell survival and death. Dysregulation of intracellular Ca(2+) levels is observed in various neuropathological states including Alzheimer's and Parkinson's diseases. Ryanodine receptors (RyRs) and inositol 1,4,5-triphosphate receptors (IP3Rs), the main Ca(2+) release channels located in endoplasmic reticulum (ER) membranes, are known to direct various cellular events such as autophagy and apoptosis. Here we investigated the intracellular Ca(2+)-mediated regulation of survival and death of adult hippocampal neural stem (HCN) cells utilizing an insulin withdrawal model of autophagic cell death (ACD). Despite comparable expression levels of RyR and IP3R transcripts in HCN cells at normal state, the expression levels of RyRs especially RyR3-were markedly upregulated upon insulin withdrawal. While treatment with the RyR agonist caffeine significantly promoted the autophagic death of insulin-deficient HCN cells, treatment with its inhibitor dantrolene prevented the induction of autophagy following insulin withdrawal. Furthermore, CRISPR/Cas9-mediated knockout of the RyR3 gene abolished ACD of HCN cells. This study delineates a distinct, RyR3-mediated ER Ca(2+) regulation of autophagy and programmed cell death in neural stem cells. Our findings provide novel insights into the critical, yet understudied mechanisms underlying the regulatory function of ER Ca(2+) in neural stem cell biology. PMID- 27199669 TI - tACS Phase Locking of Frontal Midline Theta Oscillations Disrupts Working Memory Performance. AB - BACKGROUND: Frontal midline theta (FMT) oscillations (4-8 Hz) are strongly related to cognitive and executive control during mental tasks such as memory processing, arithmetic problem solving or sustained attention. While maintenance of temporal order information during a working memory (WM) task was recently linked to FMT phase, a positive correlation between FMT power, WM demand and WM performance was shown. However, the relationship between these measures is not well understood, and it is unknown whether purposeful FMT phase manipulation during a WM task impacts FMT power and WM performance. Here we present evidence that FMT phase manipulation mediated by transcranial alternating current stimulation (tACS) can block WM demand-related FMT power increase (FMTDeltapower) and disrupt normal WM performance. METHODS: Twenty healthy volunteers were assigned to one of two groups (group A, group B) and performed a 2-back task across a baseline block (block 1) and an intervention block (block 2) while 275 sensor magnetoencephalography (MEG) was recorded. After no stimulation was applied during block 1, participants in group A received tACS oscillating at their individual FMT frequency over the prefrontal cortex (PFC) while group B received sham stimulation during block 2. After assessing and mapping phase locking values (PLV) between the tACS signal and brain oscillatory activity across the whole brain, FMT power and WM performance were assessed and compared between blocks and groups. RESULTS: During block 2 of group A but not B, FMT oscillations showed increased PLV across task-related cortical areas underneath the frontal tACS electrode. While WM task-related FMTDeltapower and WM performance were comparable across groups in block 1, tACS resulted in lower FMTDeltapower and WM performance compared to sham stimulation in block 2. CONCLUSION: tACS-related manipulation of FMT phase can disrupt WM performance and influence WM task-related FMTDeltapower. This finding may have important implications for the treatment of brain disorders such as depression and attention deficit disorder associated with abnormal regulation of FMT activity or disorders characterized by dysfunctional coupling of brain activity, e.g., epilepsy, Alzheimer's or Parkinson's disease (AD/PD). PMID- 27199667 TI - Potentiation of Gamma Aminobutyric Acid Receptors (GABAAR) by Ethanol: How Are Inhibitory Receptors Affected? AB - In recent years there has been an increase in the understanding of ethanol actions on the type A gamma-aminobutyric acid chloride channel (GABAAR), a member of the pentameric ligand gated ion channels (pLGICs). However, the mechanism by which ethanol potentiates the complex is still not fully understood and a number of publications have shown contradictory results. Thus many questions still remain unresolved requiring further studies for a better comprehension of this effect. The present review concentrates on the involvement of GABAAR in the acute actions of ethanol and specifically focuses on the immediate, direct or indirect, synaptic and extra-synaptic modulatory effects. To elaborate on the immediate, direct modulation of GABAAR by acute ethanol exposure, electrophysiological studies investigating the importance of different subunits, and data from receptor mutants will be examined. We will also discuss the nature of the putative binding sites for ethanol based on structural data obtained from other members of the pLGICs family. Finally, we will briefly highlight the glycine gated chloride channel (GlyR), another member of the pLGIC family, as a suitable target for the development of new pharmacological tools. PMID- 27199671 TI - Afferent Connectivity of the Zebrafish Habenulae. AB - The habenulae are bilateral nuclei located in the dorsal diencephalon that are conserved across vertebrates. Here we describe the main afferents to the habenulae in larval and adult zebrafish. We observe afferents from the subpallium, nucleus rostrolateralis, posterior tuberculum, posterior hypothalamic lobe, median raphe; we also see asymmetric afferents from olfactory bulb to the right habenula, and from the parapineal to the left habenula. In addition, we find afferents from a ventrolateral telencephalic nucleus that neurochemical and hodological data identify as the ventral entopeduncular nucleus (vENT), confirming and extending observations of Amo et al. (2014). Fate map and marker studies suggest that vENT originates from the diencephalic prethalamic eminence and extends into the lateral telencephalon from 48 to 120 hour post-fertilization (hpf). No afferents to the habenula were observed from the dorsal entopeduncular nucleus (dENT). Consequently, we confirm that the vENT (and not the dENT) should be considered as the entopeduncular nucleus "proper" in zebrafish. Furthermore, comparison with data in other vertebrates suggests that the vENT is a conserved basal ganglia nucleus, being homologous to the entopeduncular nucleus of mammals (internal segment of the globus pallidus of primates) by both embryonic origin and projections, as previously suggested by Amo et al. (2014). PMID- 27199670 TI - The Diversity of Cortical Inhibitory Synapses. AB - The most typical and well known inhibitory action in the cortical microcircuit is a strong inhibition on the target neuron by axo-somatic synapses. However, it has become clear that synaptic inhibition in the cortex is much more diverse and complicated. Firstly, at least ten or more inhibitory non-pyramidal cell subtypes engage in diverse inhibitory functions to produce the elaborate activity characteristic of the different cortical states. Each distinct non-pyramidal cell subtype has its own independent inhibitory function. Secondly, the inhibitory synapses innervate different neuronal domains, such as axons, spines, dendrites and soma, and their inhibitory postsynaptic potential (IPSP) size is not uniform. Thus, cortical inhibition is highly complex, with a wide variety of anatomical and physiological modes. Moreover, the functional significance of the various inhibitory synapse innervation styles and their unique structural dynamic behaviors differ from those of excitatory synapses. In this review, we summarize our current understanding of the inhibitory mechanisms of the cortical microcircuit. PMID- 27199672 TI - Phasic and Tonic mGlu7 Receptor Activity Modulates the Thalamocortical Network. AB - Mutation of the metabotropic glutamate receptor type 7 (mGlu7) induces absence like epileptic seizures, but its precise role in the somatosensory thalamocortical network remains unknown. By combining electrophysiological recordings, optogenetics, and pharmacology, we dissected the contribution of the mGlu7 receptor at mouse thalamic synapses. We found that mGlu7 is functionally expressed at both glutamatergic and GABAergic synapses, where it can inhibit neurotransmission and regulate short-term plasticity. These effects depend on the PDZ-ligand of the receptor, as they are lost in mutant mice. Interestingly, the very low affinity of mGlu7 receptors for glutamate raises the question of how it can be activated, namely at GABAergic synapses and in basal conditions. Inactivation of the receptor activity with the mGlu7 negative allosteric modulator (NAM), ADX71743, enhances thalamic synaptic transmission. In vivo administration of the NAM induces a lethargic state with spindle and/or spike-and wave discharges accompanied by a behavioral arrest typical of absence epileptic seizures. This provides evidence for mGlu7 receptor-mediated tonic modulation of a physiological function in vivo preventing synchronous and potentially pathological oscillations. PMID- 27199676 TI - Phospho-Tau and Cognitive Decline in Alzheimer's Disease. Commentary: Tau in physiology and pathology. PMID- 27199677 TI - Diffusion Tractography in Deep Brain Stimulation Surgery: A Review. AB - Deep brain stimulation (DBS) is believed to exert its therapeutic effects through modulation of brain circuitry, yet conventional preoperative planning does not allow direct targeting or visualization of white matter pathways. Diffusion MRI tractography (DT) is virtually the only non-invasive method of visualizing structural connectivity in the brain, leading many to suggest its use to guide DBS targeting. DT-guided DBS not only has the potential to allow direct white matter targeting for established applications [e.g., Parkinson's disease (PD), essential tremor (ET), dystonia], but may also aid in the discovery of new therapeutic targets for a variety of other neurologic and psychiatric diseases. Despite these exciting opportunities, DT lacks standardization and rigorous anatomic validation, raising significant concern for the use of such data in stereotactic brain surgery. This review covers the technical details, proposed methods, and initial clinical data for the use of DT in DBS surgery. Rather than focusing on specific disease applications, this review focuses on methods that can be applied to virtually any DBS target. PMID- 27199673 TI - Chandelier Cells in Functional and Dysfunctional Neural Circuits. AB - Chandelier cells (ChCs; also called axo-axonic cells) are a specialized GABAergic interneuron subtype that selectively innervates pyramidal neurons at the axon initial segment (AIS), the site of action potential generation. ChC connectivity allows for powerful yet precise modulation of large populations of pyramidal cells, suggesting ChCs have a critical role in brain functions. Dysfunctions in ChC connectivity are associated with brain disorders such as epilepsy and schizophrenia; however, whether this is causative, contributory or compensatory is not known. A likely stumbling block toward mechanistic discoveries and uncovering potential therapeutic targets is the apparent lack of rudimentary understanding of ChCs. For example, whether cortical ChCs are inhibitory or excitatory remains unresolved, and thus whether altered ChC activity results in altered inhibition or excitation is not clear. Recent studies have shed some light onto this excitation-inhibition controversy. In addition, new findings have identified preferential cell-type connectivities established by cortical ChCs, greatly expanding our understanding of the role of ChCs in the cortical microcircuit. Here we aim to bring more attention to ChC connectivity to better understand its role in neural circuits, address whether ChCs are inhibitory or excitatory in light of recent findings and discuss ChC dysfunctions in brain disorders. PMID- 27199674 TI - Theory of Connectivity: Nature and Nurture of Cell Assemblies and Cognitive Computation. AB - Richard Semon and Donald Hebb are among the firsts to put forth the notion of cell assembly-a group of coherently or sequentially-activated neurons-to represent percept, memory, or concept. Despite the rekindled interest in this century-old idea, the concept of cell assembly still remains ill-defined and its operational principle is poorly understood. What is the size of a cell assembly? How should a cell assembly be organized? What is the computational logic underlying Hebbian cell assemblies? How might Nature vs. Nurture interact at the level of a cell assembly? In contrast to the widely assumed randomness within the mature but naive cell assembly, the Theory of Connectivity postulates that the brain consists of the developmentally pre-programmed cell assemblies known as the functional connectivity motif (FCM). Principal cells within such FCM is organized by the power-of-two-based mathematical principle that guides the construction of specific-to-general combinatorial connectivity patterns in neuronal circuits, giving rise to a full range of specific features, various relational patterns, and generalized knowledge. This pre-configured canonical computation is predicted to be evolutionarily conserved across many circuits, ranging from these encoding memory engrams and imagination to decision-making and motor control. Although the power-of-two-based wiring and computational logic places a mathematical boundary on an individual's cognitive capacity, the fullest intellectual potential can be brought about by optimized nature and nurture. This theory may also open up a new avenue to examining how genetic mutations and various drugs might impair or improve the computational logic of brain circuits. PMID- 27199678 TI - Retinal Changes in an ATP-Induced Model of Retinal Degeneration. AB - In rodents and felines, intravitreal administration of adenosine triphosphate (ATP) has been shown to induce photoreceptor death providing a tractable model of retinal degeneration in these species. This study investigated the long term effects of photoreceptor loss in an ATP induced feline model of retinal degeneration. Six normal sighted felines were unilaterally blinded using intravitreal ATP injections and assessed using electroretinography (ERG) and optical coherence tomography (OCT). At 30 h (n = 3) or 12 weeks (n = 3) post injection, the animals were euthanized and the eyes enucleated. Retinae were sectioned and labeled using immunohistochemistry for markers of cell death, neural remodeling and gliosis. Ongoing cell death and retinal degeneration was observed in the outer retina at both 30 h and 12 weeks following unilateral ATP injection. Markers of mid to late-stage retinal remodeling such as cell displacement and aberrant neurite growth were observed in the inner retina at 12 weeks post-injection. Ganglion cells appeared to remain intact in ATP injected eyes. Muller cell gliosis was observed throughout the inner and outer retina, in some parts completely enveloping and/or displacing the surviving neural tissue. Our data suggests that the ATP injected feline retina continues to undergo progressive retinal degeneration and exhibits abnormalities consistent with a description of retinal remodeling commonly seen in other models of retinal degeneration. These findings validate the use of intravitreal ATP injection in feline as a large animal model of retinal degeneration which may aid in development of therapies aiming to restore visual function after photoreceptor degeneration. PMID- 27199675 TI - Inhibitory Circuits in Cortical Layer 5. AB - Inhibitory neurons play a fundamental role in cortical computation and behavior. Recent technological advances, such as two photon imaging, targeted in vivo recording, and molecular profiling, have improved our understanding of the function and diversity of cortical interneurons, but for technical reasons most work has been directed towards inhibitory neurons in the superficial cortical layers. Here we review current knowledge specifically on layer 5 (L5) inhibitory microcircuits, which play a critical role in controlling cortical output. We focus on recent work from the well-studied rodent barrel cortex, but also draw on evidence from studies in primary visual cortex and other cortical areas. The diversity of both deep inhibitory neurons and their pyramidal cell targets make this a challenging but essential area of study in cortical computation and sensory processing. PMID- 27199679 TI - Distribution of Cytoglobin in the Mouse Brain. AB - Cytoglobin (Cygb) is a vertebrate globin with so far poorly defined function. It is expressed in the fibroblast cell-lineage but has also been found in neurons. Here we provide, using immunohistochemistry, a detailed study on the distribution of Cygb in the mouse brain. While Cygb is a cytoplasmic protein in active cells of the supportive tissue, in neurons it is located in the cytoplasm and the nucleus. We found the expression of Cygb in all brain regions, although only a fraction of the neurons was Cygb-positive. Signals were of different intensity ranging from faint to very intense. Telencephalic neurons in all laminae of the cerebral cortex (CCo), in the olfactory bulb (in particular periglomerular cells), in the hippocampal formation (strongly stained pyramidal cells with long processes), basal ganglia (scattered multipolar neurons in the dorsal striatum, dorsal and ventral pallidum (VP)), and in the amygdala (neurons with unlabeled processes) were labeled by the antibody. In the diencephalon, we observed Cygb positive neurons of moderate intensity in various nuclei of the dorsal thalamus, in the hypothalamus, metathalamus (geniculate nuclei), epithalamus with strong labeling of habenular nucleus neurons and no labeling of pineal cells, and in the ventral thalamus. Tegmental neurons stood out by strongly stained somata with long processes in, e.g., the laterodorsal nucleus. In the tectum, faintly labeled neurons and fibers were detected in the superior colliculus (SC). The cerebellum exhibited unlabeled Purkinje-neurons but signs of strong afferent cortical innervation. Neurons in the gray matter of the spinal cord showed moderate immunofluorescence. Peripheral ganglia were not labeled by the antibody. The Meynert-fascicle and the olfactory and optic nerves/tracts were the only Cygb immunoreactive (Cygb-IR) fiber systems. Notably, we found a remarkable level of colocalization of Cygb and neuronal nitric oxide (NO)-synthase in neurons, which supports a functional association. PMID- 27199680 TI - Neuronal Organization of Deep Brain Opsin Photoreceptors in Adult Teleosts. AB - Biological impacts of light beyond vision, i.e., non-visual functions of light, signify the need to better understand light detection (or photoreception) systems in vertebrates. Photopigments, which comprise light-absorbing chromophores bound to a variety of G-protein coupled receptor opsins, are responsible for visual and non-visual photoreception. Non-visual opsin photopigments in the retina of mammals and extra-retinal tissues of non-mammals play an important role in non image-forming functions of light, e.g., biological rhythms and seasonal reproduction. This review highlights the role of opsin photoreceptors in the deep brain, which could involve conserved neurochemical systems that control different time- and light-dependent physiologies in in non-mammalian vertebrates including teleost fish. PMID- 27199682 TI - 3D Reconstructed Cyto-, Muscarinic M2 Receptor, and Fiber Architecture of the Rat Brain Registered to the Waxholm Space Atlas. AB - High-resolution multiscale and multimodal 3D models of the brain are essential tools to understand its complex structural and functional organization. Neuroimaging techniques addressing different aspects of brain organization should be integrated in a reference space to enable topographically correct alignment and subsequent analysis of the various datasets and their modalities. The Waxholm Space (http://software.incf.org/software/waxholm-space) is a publicly available 3D coordinate-based standard reference space for the mapping and registration of neuroanatomical data in rodent brains. This paper provides a newly developed pipeline combining imaging and reconstruction steps with a novel registration strategy to integrate new neuroimaging modalities into the Waxholm Space atlas. As a proof of principle, we incorporated large scale high-resolution cyto-, muscarinic M2 receptor, and fiber architectonic images of rat brains into the 3D digital MRI based atlas of the Sprague Dawley rat in Waxholm Space. We describe the whole workflow, from image acquisition to reconstruction and registration of these three modalities into the Waxholm Space rat atlas. The registration of the brain sections into the atlas is performed by using both linear and non-linear transformations. The validity of the procedure is qualitatively demonstrated by visual inspection, and a quantitative evaluation is performed by measurement of the concordance between representative atlas-delineated regions and the same regions based on receptor or fiber architectonic data. This novel approach enables for the first time the generation of 3D reconstructed volumes of nerve fibers and fiber tracts, or of muscarinic M2 receptor density distributions, in an entire rat brain. Additionally, our pipeline facilitates the inclusion of further neuroimaging datasets, e.g., 3D reconstructed volumes of histochemical stainings or of the regional distributions of multiple other receptor types, into the Waxholm Space. Thereby, a multiscale and multimodal rat brain model was created in the Waxholm Space atlas of the rat brain. Since the registration of these multimodal high-resolution datasets into the same coordinate system is an indispensable requisite for multi-parameter analyses, this approach enables combined studies on receptor and cell distributions as well as fiber densities in the same anatomical structures at microscopic scales for the first time. PMID- 27199681 TI - Eppur Si Muove: Evidence for an External Granular Layer and Possibly Transit Amplification in the Teleostean Cerebellum. AB - The secreted signaling factor Sonic Hedgehog (Shh) acts in the floor plate of the developing vertebrate CNS to promote motoneuron development. In addition, shh has dorsal expression domains in the amniote alar plate (i.e., in isocortex, superior colliculus, and cerebellum). For example, shh expressing Purkinje cells act in transit amplification of external granular layer (EGL) cells of the developing cerebellum. Our previous studies had indicated the presence of an EGL in anamniote zebrafish, but a possible role of shh in the zebrafish cerebellar plate remained elusive. Therefore, we used an existing zebrafish transgenic line Tg(2.4shha-ABC-GFP)sb15; Shkumatava et al., 2004) to show this gene activity and its cellular localization in the larval zebrafish brain. Clearly, GFP expressing cells occur in larval alar zebrafish brain domains, i.e., optic tectum and cerebellum. Analysis of critical cerebellar cell markers on this transgenic background and a PH3 assay for mitotic cells reveals that Purkinje cells and eurydendroid cells are completely non-overlapping postmitotic cell populations. Furthermore, shh-GFP cells never express Zebrin II or parvalbumin, nor calretinin. They are thus neither Purkinje cells nor calretinin positive migrating rhombic lip derived cells. The shh-GFP cells also never correspond to PH3 positive cells of the ventral cerebellar proliferative zone or the upper rhombic lip-derived EGL. From this marker analysis and the location of shh-GFP cells sandwiched between calretinin positive rhombic lip derived cells and parvalbumin positive Purkinje cells, we conclude that shh-GFP expressing cells qualify as previously reported olig2 positive eurydendroid cells, which are homologous to the amniote deep cerebellar nuclei. We confirm this using double transgenic progeny of shh-GFP and olig2-dsRed zebrafish. Thus, these zebrafish eurydendroid cells may have the same role in transit amplification as Purkinje cells do in amniotes. PMID- 27199683 TI - Corrigendum: Unexpected Variation in Neuroanatomy among Diverse Nematode Species. AB - [This corrects the article on p. 162 in vol. 9, PMID: 26778973.]. PMID- 27199686 TI - Commentary: Sensory integration dynamics in a hierarchical network explains choice probabilities in cortical area MT. PMID- 27199685 TI - Traumatic Brain Injury Alters Methionine Metabolism: Implications for Pathophysiology. AB - Methionine is an essential proteinogenic amino acid that is obtained from the diet. In addition to its requirement for protein biosynthesis, methionine is metabolized to generate metabolites that play key roles in a number of cellular functions. Metabolism of methionine via the transmethylation pathway generates S adenosylmethionine (SAM) that serves as the principal methyl (-CH3) donor for DNA and histone methyltransferases (MTs) to regulate epigenetic changes in gene expression. SAM is also required for methylation of other cellular proteins that serve various functions and phosphatidylcholine synthesis that participate in cellular signaling. Under conditions of oxidative stress, homocysteine (which is derived from SAM) enters the transsulfuration pathway to generate glutathione, an important cytoprotective molecule against oxidative damage. As both experimental and clinical studies have shown that traumatic brain injury (TBI) alters DNA and histone methylation and causes oxidative stress, we examined if TBI alters the plasma levels of methionine and its metabolites in human patients. Blood samples were collected from healthy volunteers (HV; n = 20) and patients with mild TBI (mTBI; GCS > 12; n = 20) or severe TBI (sTBI; GCS < 8; n = 20) within the first 24 h of injury. The levels of methionine and its metabolites in the plasma samples were analyzed by either liquid chromatography-mass spectrometry or gas chromatography-mass spectrometry (LC-MS or GC-MS). sTBI decreased the levels of methionine, SAM, betaine and 2-methylglycine as compared to HV, indicating a decrease in metabolism through the transmethylation cycle. In addition, precursors for the generation of glutathione, cysteine and glycine were also found to be decreased as were intermediate metabolites of the gamma-glutamyl cycle (gamma-glutamyl amino acids and 5-oxoproline). mTBI also decreased the levels of methionine, alpha-ketobutyrate, 2 hydroxybutyrate and glycine, albeit to lesser degrees than detected in the sTBI group. Taken together, these results suggest that decreased levels of methionine and its metabolic products are likely to alter cellular function in multiple organs at a systems level. PMID- 27199687 TI - Corrigendum: Functional Activation in the Ventral Object Processing Pathway during the First Year. AB - [This corrects the article on p. 180 in vol. 9, PMID: 26778979.]. PMID- 27199688 TI - The Nature and Function of Digital Information Compression Mechanisms in the Brain and in Digital Television Technology. PMID- 27199690 TI - Dynamic Echo Information Guides Flight in the Big Brown Bat. AB - Animals rely on sensory feedback from their environment to guide locomotion. For instance, visually guided animals use patterns of optic flow to control their velocity and to estimate their distance to objects (e.g., Srinivasan et al., 1991, 1996). In this study, we investigated how acoustic information guides locomotion of animals that use hearing as a primary sensory modality to orient and navigate in the dark, where visual information is unavailable. We studied flight and echolocation behaviors of big brown bats as they flew under infrared illumination through a corridor with walls constructed from a series of individual vertical wooden poles. The spacing between poles on opposite walls of the corridor was experimentally manipulated to create dense/sparse and balanced/imbalanced spatial structure. The bats' flight trajectories and echolocation signals were recorded with high-speed infrared motion-capture cameras and ultrasound microphones, respectively. As bats flew through the corridor, successive biosonar emissions returned cascades of echoes from the walls of the corridor. The bats flew through the center of the corridor when the pole spacing on opposite walls was balanced and closer to the side with wider pole spacing when opposite walls had an imbalanced density. Moreover, bats produced shorter duration echolocation calls when they flew through corridors with smaller spacing between poles, suggesting that clutter density influences features of the bat's sonar signals. Flight speed and echolocation call rate did not, however, vary with dense and sparse spacing between the poles forming the corridor walls. Overall, these data demonstrate that bats adapt their flight and echolocation behavior dynamically when flying through acoustically complex environments. PMID- 27199684 TI - More Gamma More Predictions: Gamma-Synchronization as a Key Mechanism for Efficient Integration of Classical Receptive Field Inputs with Surround Predictions. AB - During visual stimulation, neurons in visual cortex often exhibit rhythmic and synchronous firing in the gamma-frequency (30-90 Hz) band. Whether this phenomenon plays a functional role during visual processing is not fully clear and remains heavily debated. In this article, we explore the function of gamma synchronization in the context of predictive and efficient coding theories. These theories hold that sensory neurons utilize the statistical regularities in the natural world in order to improve the efficiency of the neural code, and to optimize the inference of the stimulus causes of the sensory data. In visual cortex, this relies on the integration of classical receptive field (CRF) data with predictions from the surround. Here we outline two main hypotheses about gamma-synchronization in visual cortex. First, we hypothesize that the precision of gamma-synchronization reflects the extent to which CRF data can be accurately predicted by the surround. Second, we hypothesize that different cortical columns synchronize to the extent that they accurately predict each other's CRF visual input. We argue that these two hypotheses can account for a large number of empirical observations made on the stimulus dependencies of gamma synchronization. Furthermore, we show that they are consistent with the known laminar dependencies of gamma-synchronization and the spatial profile of intercolumnar gamma-synchronization, as well as the dependence of gamma synchronization on experience and development. Based on our two main hypotheses, we outline two additional hypotheses. First, we hypothesize that the precision of gamma-synchronization shows, in general, a negative dependence on RF size. In support, we review evidence showing that gamma-synchronization decreases in strength along the visual hierarchy, and tends to be more prominent in species with small V1 RFs. Second, we hypothesize that gamma-synchronized network dynamics facilitate the emergence of spiking output that is particularly information-rich and sparse. PMID- 27199689 TI - Hand-Camera Coordination Varies over Time in Users of the Argus((r)) II Retinal Prosthesis System. AB - INTRODUCTION: Most visual neuroprostheses use an external camera for image acquisition. This adds two complications to phosphene perception: (1) stimulation locus will not change with eye movements; and (2) external cameras can be aimed in directions different from the user's intended direction of gaze. Little is known about the stability of where users perceive light sources to be or whether they will adapt to changes in camera orientation. METHODS: Three end-stage retinitis pigmentosa patients implanted with the Argus II participated in this study. This prosthesis stimulated the retina based on an 18 degrees * 11 degrees area selected within the camera's 66 degrees * 49 degrees field of view. The center of the electrode array's field of view mapped within the camera's field of view is the camera alignment position (CAP). Proper camera alignments minimize errors in localizing visual percepts in space. Subjects touched single white squares in random locations on a darkened touchscreen 40 or more times. To study adaptation, subjects were given intentional CAP misalignments of 15-40 degrees for 5-6 months. Subjects performed this test with auditory feedback during (bi )weekly lab sessions. Misaligned CAPs were maintained for another 5-6 months without auditory feedback. Touch alignment was tracked to detect any adaptation. To estimate localization stability, data for when CAPs were set to minimize errors were tracked. The same localization test as above was used. Localization errors were tracked every 1-2 weeks for up to 40 months. RESULTS: Two of three subjects used auditory feedback to improve accuracy with misaligned CAPs at an average rate of 0.02 degrees /day (p < 0.05, bootstrap analysis of linear regression). The rates observed here were ~4000 times slower than those seen in normally-sighted subjects adapting to prism glasses. Removal of auditory feedback precipitated error increases for all subjects. Optimal CAPs varied significantly across test sessions (p < 10(-4), bootstrap multivariate analysis of variance (MANOVA)), up to 21-29 degrees within subjects over the observed period. Across subjects, optimal CAPs showed an average rate of change of 0.39 degrees /day (SD 0.36 degrees /day). CONCLUSIONS: Optimal CAPs varied dramatically over time for all subjects. Subjects displayed no adaptation to misaligned CAPs without feedback. Regular recalibration of CAPs may be required to maintain hand-camera coordination. PMID- 27199691 TI - To Cheat or Not To Cheat: Tryptophan Hydroxylase 2 SNP Variants Contribute to Dishonest Behavior. AB - Although, lying (bear false witness) is explicitly prohibited in the Decalogue and a focus of interest in philosophy and theology, more recently the behavioral and neural mechanisms of deception are gaining increasing attention from diverse fields especially economics, psychology, and neuroscience. Despite the considerable role of heredity in explaining individual differences in deceptive behavior, few studies have investigated which specific genes contribute to the heterogeneity of lying behavior across individuals. Also, little is known concerning which specific neurotransmitter pathways underlie deception. Toward addressing these two key questions, we implemented a neurogenetic strategy and modeled deception by an incentivized die-under-cup task in a laboratory setting. The results of this exploratory study provide provisional evidence that SNP variants across the tryptophan hydroxylase 2 (TPH2) gene, that encodes the rate limiting enzyme in the biosynthesis of brain serotonin, contribute to individual differences in deceptive behavior. PMID- 27199692 TI - Persistent Impact of In utero Irradiation on Mouse Brain Structure and Function Characterized by MR Imaging and Behavioral Analysis. AB - Prenatal irradiation is known to perturb brain development. Epidemiological studies revealed that radiation exposure during weeks 8-15 of pregnancy was associated with an increased occurrence of mental disability and microcephaly. Such neurological deficits were reproduced in animal models, in which rodent behavioral testing is an often used tool to evaluate radiation-induced defective brain functionality. However, up to now, animal studies suggested a threshold dose of around 0.30 Gray (Gy) below which no behavioral alterations can be observed, while human studies hinted at late defects after exposure to doses as low as 0.10 Gy. Here, we acutely irradiated pregnant mice at embryonic day 11 with doses ranging from 0.10 to 1.00 Gy. A thorough investigation of the dose response relationship of altered brain function and architecture following in utero irradiation was achieved using a behavioral test battery and volumetric 3D T2-weighted magnetic resonance imaging (MRI). We found dose-dependent changes in cage activity, social behavior, anxiety-related exploration, and spatio-cognitive performance. Although behavioral alterations in low-dose exposed animals were mild, we did unveil that both emotionality and higher cognitive abilities were affected in mice exposed to >=0.10 Gy. Microcephaly was apparent from 0.33 Gy onwards and accompanied by deviations in regional brain volumes as compared to controls. Of note, total brain volume and the relative volume of the ventricles, frontal and posterior cerebral cortex, cerebellum, and striatum were most strongly correlated to altered behavioral parameters. Taken together, we present conclusive evidence for persistent low-dose effects after prenatal irradiation in mice and provide a better understanding of the correlation between their brain size and performance in behavioral tests. PMID- 27199694 TI - Mapping of the Underlying Neural Mechanisms of Maintenance and Manipulation in Visuo-Spatial Working Memory Using An n-back Mental Rotation Task: A Functional Magnetic Resonance Imaging Study. AB - Mapping of the underlying neural mechanisms of visuo-spatial working memory (WM) has been shown to consistently elicit activity in right hemisphere dominant fronto-parietal networks. However to date, the bulk of neuroimaging literature has focused largely on the maintenance aspect of visuo-spatial WM, with a scarcity of research into the aspects of WM involving manipulation of information. Thus, this study aimed to compare maintenance-only with maintenance and manipulation of visuo-spatial stimuli (3D cube shapes) utilizing a 1-back task while functional magnetic resonance imaging (fMRI) scans were acquired. Sixteen healthy participants (9 women, M = 23.94 years, SD = 2.49) were required to perform the 1-back task with or without mentally rotating the shapes 90 degrees on a vertical axis. When no rotation was required (maintenance-only condition), a right hemispheric lateralization was revealed across fronto parietal areas. However, when the task involved maintaining and manipulating the same stimuli through 90 degrees rotation, activation was primarily seen in the bilateral parietal lobe and left fusiform gyrus. The findings confirm that the well-established right lateralized fronto-parietal networks are likely to underlie simple maintenance of visuo-spatial stimuli. The results also suggest that the added demand of manipulation of information maintained online appears to require further neural recruitment of functionally related areas. In particular mental rotation of visuospatial stimuli required bilateral parietal areas, and the left fusiform gyrus potentially to maintain a categorical or object representation. It can be concluded that WM is a complex neural process involving the interaction of an increasingly large network. PMID- 27199695 TI - How to Link Brain and Experience? Spatiotemporal Psychopathology of the Lived Body. AB - The focus of the present article is on sketching a psychopathology of the body in schizophrenia and linking it to brain activity. This is done providing converging data from psychopathological evidence (phenomenal), phenomenological contructs (trans-phenomenal) and neuroscientific measures (pre-phenomenal). The phenomenal level is the detailed documentation of the patients' subjective anomalous experiences. These phenomena are explicit contents in the patients' field of consciousness. The trans-phenomenal level targets the implicit yet operative matrix that underlies these anomalous subjective experiences. Abnormal phenomena are viewed as expressions of a modification of trans-phenomenal matrix, that is, in terms of an abnormal synthesis or integration through time of intero-, proprio and extero-ceptive stimuli. Finally, we link the abnormalities of the trans phenomenal matrix to pre-phenomenal alterations of the brain resting state and of its spatio-temporal organization, as documented by neurobiological methods providing spatial and temporal resolution of intrinsic brain activity (with many features of the resting state remaining yet unclear though). Based on phenomenological research, the body in schizophrenia is typically experienced in an itemized way as an object external to one's self and unrelated to events in the external world. Based on neurobiological data, we tentatively hypothesize that such anomalies of the lived body are related to decreased integration between intero-, extero- and proprioceptive experiences by the brain's spontaneous activity and its temporal structure. Taken all together, this suggests that we view abnormalities of bodily experience in terms of their underlying abnormal spatiotemporal features which, as we suppose, can be traced back to the spatiotemporal features of the brain's spontaneous activity. PMID- 27199696 TI - Do Differences in Levels, Types, and Duration of Muscle Contraction Have an Effect on the Degree of Post-exercise Depression? AB - We conducted two experiments to determine how differences in muscle contraction levels, muscle contraction types, and movement duration affect degree of post exercise depression (PED) after non-exhaustive, repetitive finger movement. Twelve healthy participants performed repetitive abduction movements of the right index finger at 2 Hz. In experiment 1, we examined the effects of muscle contraction levels at 10, 20, and 30% maximum voluntary contraction and the effects of muscle contraction types at isotonic and isometric contraction. In experiment 2, we examined the effects of movement duration at 2 and 6 min. Motor evoked potentials (MEPs) were recorded from the right first dorsal interosseous muscle before movement tasks and 1-10 min after movement tasks. MEP amplitudes after isotonic contraction tasks were significantly smaller than those after isometric contraction tasks and decreased with increasing contraction levels, but were independent of movement duration. This study demonstrated that the degree of PED after non-exhaustive repetitive finger movement depended on muscle contraction levels and types. Thus, the degree of PED may depend on the levels of activity in the motor cortex during a movement task. This knowledge will aid in the design of rehabilitation protocols. PMID- 27199693 TI - STN-DBS Reduces Saccadic Hypometria but Not Visuospatial Bias in Parkinson's Disease Patients. AB - In contrast to its well-established role in alleviating skeleto-motor symptoms in Parkinson's disease, little is known about the impact of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on oculomotor control and attention. Eye tracking data of 17 patients with left-hemibody symptom onset was compared with 17 age-matched control subjects. Free-viewing of natural images was assessed without stimulation as baseline and during bilateral DBS. To examine the involvement of ventral STN territories in oculomotion and spatial attention, we employed unilateral stimulation via the left and right ventralmost contacts respectively. When DBS was off, patients showed shorter saccades and a rightward viewing bias compared with controls. Bilateral stimulation in therapeutic settings improved saccadic hypometria but not the visuospatial bias. At a group level, unilateral ventral stimulation yielded no consistent effects. However, the evaluation of electrode position within normalized MNI coordinate space revealed that the extent of early exploration bias correlated with the precise stimulation site within the left subthalamic area. These results suggest that oculomotor impairments "but not higher-level exploration patterns" are effectively ameliorable by DBS in therapeutic settings. Our findings highlight the relevance of the STN topography in selecting contacts for chronic stimulation especially upon appearance of visuospatial attention deficits. PMID- 27199697 TI - Visualizing the Impact of Art: An Update and Comparison of Current Psychological Models of Art Experience. AB - The last decade has witnessed a renaissance of empirical and psychological approaches to art study, especially regarding cognitive models of art processing experience. This new emphasis on modeling has often become the basis for our theoretical understanding of human interaction with art. Models also often define areas of focus and hypotheses for new empirical research, and are increasingly important for connecting psychological theory to discussions of the brain. However, models are often made by different researchers, with quite different emphases or visual styles. Inputs and psychological outcomes may be differently considered, or can be under-reported with regards to key functional components. Thus, we may lose the major theoretical improvements and ability for comparison that can be had with models. To begin addressing this, this paper presents a theoretical assessment, comparison, and new articulation of a selection of key contemporary cognitive or information-processing-based approaches detailing the mechanisms underlying the viewing of art. We review six major models in contemporary psychological aesthetics. We in turn present redesigns of these models using a unified visual form, in some cases making additions or creating new models where none had previously existed. We also frame these approaches in respect to their targeted outputs (e.g., emotion, appraisal, physiological reaction) and their strengths within a more general framework of early, intermediate, and later processing stages. This is used as a basis for general comparison and discussion of implications and future directions for modeling, and for theoretically understanding our engagement with visual art. PMID- 27199700 TI - Editorial: Neural Mechanisms Underlying Movement-Based Embodied Contemplative Practices. PMID- 27199699 TI - Foreign Accent Syndrome As a Psychogenic Disorder: A Review. AB - In the majority of cases published between 1907 and 2014, FAS is due to a neurogenic etiology. Only a few reports about FAS with an assumed psychogenic origin have been published. The present article discusses the findings of a careful database search on psychogenic FAS. This review may be particularly relevant as it is the first to analyze the salient features of psychogenic FAS cases to date. This article hopes to pave the way for the view that psychogenic FAS is a cognate of neurogenic FAS. It is felt that this variant of FAS may have been underreported, as most of the psychogenic cases have been published after the turn of the century. This review may improve the diagnosis of the syndrome in clinical practice and highlights the importance of recognizing psychogenic FAS as an independent taxonomic entity. PMID- 27199698 TI - Greater Repertoire and Temporal Variability of Cross-Frequency Coupling (CFC) Modes in Resting-State Neuromagnetic Recordings among Children with Reading Difficulties. AB - Cross-frequency, phase-to-amplitude coupling (PAC) between neuronal oscillations at rest may serve as the substrate that supports information exchange between functionally specialized neuronal populations both within and between cortical regions. The study utilizes novel algorithms to identify prominent instantaneous modes of cross-frequency coupling and their temporal stability in resting state magnetoencephalography (MEG) data from 25 students experiencing severe reading difficulties (RD) and 27 age-matched non-impaired readers (NI). Phase coherence estimates were computed in order to identify the prominent mode of PAC interaction for each sensor, sensor pair, and pair of frequency bands (from delta to gamma) at successive time windows of the continuous MEG record. The degree of variability in the characteristic frequency-pair PAC(f1-f2) modes over time was also estimated. Results revealed a wider repertoire of prominent PAC interactions in RD as compared to NI students, suggesting an altered functional substrate for information exchange between neuronal assemblies in the former group. Moreover, RD students showed significant variability in PAC modes over time. This temporal instability of PAC values was particularly prominent: (a) within and between right hemisphere temporo-parietal and occipito-temporal sensors and, (b) between left hemisphere frontal, temporal, and occipito-temporal sensors and corresponding right hemisphere sites. Altered modes of neuronal population coupling may help account for extant data revealing reduced, task-related neurophysiological and hemodynamic activation in left hemisphere regions involved in the reading network in RD. Moreover, the spatial distribution of pronounced instability of cross-frequency coupling modes in this group may provide an explanation for previous reports suggesting the presence of inefficient compensatory mechanisms to support reading. PMID- 27199703 TI - Editorial: Perceiving and Acting in the Real World: From Neural Activity to Behavior. PMID- 27199701 TI - Pre-Trial EEG-Based Single-Trial Motor Performance Prediction to Enhance Neuroergonomics for a Hand Force Task. AB - We propose a framework for building electrophysiological predictors of single trial motor performance variations, exemplified for SVIPT, a sequential isometric force control task suitable for hand motor rehabilitation after stroke. Electroencephalogram (EEG) data of 20 subjects with mean age of 53 years was recorded prior to and during 400 trials of SVIPT. They were executed within a single session with the non-dominant left hand, while receiving continuous visual feedback of the produced force trajectories. The behavioral data showed strong trial-by-trial performance variations for five clinically relevant metrics, which accounted for reaction time as well as for the smoothness and precision of the produced force trajectory. 18 out of 20 tested subjects remained after preprocessing and entered offline analysis. Source Power Comodulation (SPoC) was applied on EEG data of a short time interval prior to the start of each SVIPT trial. For 11 subjects, SPoC revealed robust oscillatory EEG subspace components, whose bandpower activity are predictive for the performance of the upcoming trial. Since SPoC may overfit to non-informative subspaces, we propose to apply three selection criteria accounting for the meaningfulness of the features. Across all subjects, the obtained components were spread along the frequency spectrum and showed a variety of spatial activity patterns. Those containing the highest level of predictive information resided in and close to the alpha band. Their spatial patterns resemble topologies reported for visual attention processes as well as those of imagined or executed hand motor tasks. In summary, we identified subject-specific single predictors that explain up to 36% of the performance fluctuations and may serve for enhancing neuroergonomics of motor rehabilitation scenarios. PMID- 27199704 TI - Do Visual and Vestibular Inputs Compensate for Somatosensory Loss in the Perception of Spatial Orientation? Insights from a Deafferented Patient. AB - The present study aimed at investigating the consequences of a massive loss of somatosensory inputs on the perception of spatial orientation. The occurrence of possible compensatory processes for external (i.e., object) orientation perception and self-orientation perception was examined by manipulating visual and/or vestibular cues. To that aim, we compared perceptual responses of a deafferented patient (GL) with respect to age-matched Controls in two tasks involving gravity-related judgments. In the first task, subjects had to align a visual rod with the gravitational vertical (i.e., Subjective Visual Vertical: SVV) when facing a tilted visual frame in a classic Rod-and-Frame Test. In the second task, subjects had to report whether they felt tilted when facing different visuo-postural conditions which consisted in very slow pitch tilts of the body and/or visual surroundings away from vertical. Results showed that, much more than Controls, the deafferented patient was fully dependent on spatial cues issued from the visual frame when judging the SVV. On the other hand, the deafferented patient did not rely at all on visual cues for self-tilt detection. Moreover, the patient never reported any sensation of tilt up to 18 degrees contrary to Controls, hence showing that she did not rely on vestibular (i.e., otoliths) signals for the detection of very slow body tilts either. Overall, this study demonstrates that a massive somatosensory deficit substantially impairs the perception of spatial orientation, and that the use of the remaining sensory inputs available to a deafferented patient differs regarding whether the judgment concerns external vs. self-orientation. PMID- 27199705 TI - Neuronal Oscillations in Various Frequency Bands Differ between Pain and Touch. AB - Although humans are generally capable of distinguishing single events of pain or touch, recent research suggested that both modalities activate a network of similar brain regions. By contrast, less attention has been paid to which processes uniquely contribute to each modality. The present study investigated the neuronal oscillations that enable a subject to process pain and touch as well as to evaluate the intensity of both modalities by means of Electroencephalography. Nineteen healthy subjects were asked to rate the intensity of each stimulus at single trial level. By computing Linear mixed effects models (LME) encoding of both modalities was explored by relating stimulus intensities to brain responses. While the intensity of single touch trials is encoded only by theta activity, pain perception is encoded by theta, alpha and gamma activity. Beta activity in the tactile domain shows an on/off like characteristic in response to touch which was not observed in the pain domain. Our results enhance recent findings pointing to the contribution of different neuronal oscillations to the processing of nociceptive and tactile stimuli. PMID- 27199702 TI - Visual Illusions: An Interesting Tool to Investigate Developmental Dyslexia and Autism Spectrum Disorder. AB - A visual illusion refers to a percept that is different in some aspect from the physical stimulus. Illusions are a powerful non-invasive tool for understanding the neurobiology of vision, telling us, indirectly, how the brain processes visual stimuli. There are some neurodevelopmental disorders characterized by visual deficits. Surprisingly, just a few studies investigated illusory perception in clinical populations. Our aim is to review the literature supporting a possible role for visual illusions in helping us understand the visual deficits in developmental dyslexia and autism spectrum disorder. Future studies could develop new tools - based on visual illusions - to identify an early risk for neurodevelopmental disorders. PMID- 27199707 TI - Flicker-Driven Responses in Visual Cortex Change during Matched-Frequency Transcranial Alternating Current Stimulation. AB - We tested a novel combination of two neuro-stimulation techniques, transcranial alternating current stimulation (tACS) and frequency tagging, that promises powerful paradigms to study the causal role of rhythmic brain activity in perception and cognition. Participants viewed a stimulus flickering at 7 or 11 Hz that elicited periodic brain activity, termed steady-state responses (SSRs), at the same temporal frequency and its higher order harmonics. Further, they received simultaneous tACS at 7 or 11 Hz that either matched or differed from the flicker frequency. Sham tACS served as a control condition. Recent advances in reconstructing cortical sources of oscillatory activity allowed us to measure SSRs during concurrent tACS, which is known to impose strong artifacts in magnetoencephalographic (MEG) recordings. For the first time, we were thus able to demonstrate immediate effects of tACS on SSR-indexed early visual processing. Our data suggest that tACS effects are largely frequency-specific and reveal a characteristic pattern of differential influences on the harmonic constituents of SSRs. PMID- 27199706 TI - Amygdala Regulation Following fMRI-Neurofeedback without Instructed Strategies. AB - Within the field of functional magnetic resonance imaging (fMRI) neurofeedback, most studies provide subjects with instructions or suggest strategies to regulate a particular brain area, while other neuro-/biofeedback approaches often do not. This study is the first to investigate the hypothesis that subjects are able to utilize fMRI neurofeedback to learn to differentially modulate the fMRI signal from the bilateral amygdala congruent with the prescribed regulation direction without an instructed or suggested strategy and apply what they learned even when feedback is no longer available. Thirty-two subjects were included in the analysis. Data were collected at 3 Tesla using blood oxygenation level dependent (BOLD)-sensitivity optimized multi-echo EPI. Based on the mean contrast between up- and down-regulation in the amygdala in a post-training scan without feedback following three neurofeedback sessions, subjects were able to regulate their amygdala congruent with the prescribed directions with a moderate effect size of Cohen's d = 0.43 (95% conf. int. 0.23-0.64). This effect size would be reduced, however, through stricter exclusion criteria for subjects that show alterations in respiration. Regulation capacity was positively correlated with subjective arousal ratings and negatively correlated with agreeableness and susceptibility to anger. A learning effect over the training sessions was only observed with end of-block feedback (EoBF) but not with continuous feedback (trend). The results confirm the above hypothesis. Further studies are needed to compare effect sizes of regulation capacity for approaches with and without instructed strategies. PMID- 27199709 TI - Sensorimotor Synchronization with Different Metrical Levels of Point-Light Dance Movements. AB - Rhythm perception and synchronization have been extensively investigated in the auditory domain, as they underlie means of human communication such as music and speech. Although recent studies suggest comparable mechanisms for synchronizing with periodically moving visual objects, the extent to which it applies to ecologically relevant information, such as the rhythm of complex biological motion, remains unknown. The present study addressed this issue by linking rhythm of music and dance in the framework of action-perception coupling. As a previous study showed that observers perceived multiple metrical periodicities in dance movements that embodied this structure, the present study examined whether sensorimotor synchronization (SMS) to dance movements resembles what is known of auditory SMS. Participants watched a point-light figure performing two basic steps of Swing dance cyclically, in which the trunk bounced at every beat and the limbs moved at every second beat, forming two metrical periodicities. Participants tapped synchronously to the bounce of the trunk with or without the limbs moving in the stimuli (Experiment 1), or tapped synchronously to the leg movements with or without the trunk bouncing simultaneously (Experiment 2). Results showed that, while synchronization with the bounce (lower-level pulse) was not influenced by the presence or absence of limb movements (metrical accent), synchronization with the legs (beat) was improved by the presence of the bounce (metrical subdivision) across different movement types. The latter finding parallels the "subdivision benefit" often demonstrated in auditory tasks, suggesting common sensorimotor mechanisms for visual rhythms in dance and auditory rhythms in music. PMID- 27199708 TI - Neural Mechanisms of Inhibitory Response in a Battlefield Scenario: A Simultaneous fMRI-EEG Study. AB - The stop-signal paradigm has been widely adopted as a way to parametrically quantify the response inhibition process. To evaluate inhibitory function in realistic environmental settings, the current study compared stop-signal responses in two different scenarios: one uses simple visual symbols as go and stop signals, and the other translates the typical design into a battlefield scenario (BFS) where a sniper-scope view was the background, a terrorist image was the go signal, a hostage image was the stop signal, and the task instructions were to shoot at terrorists only when hostages were not present but to refrain from shooting if hostages appeared. The BFS created a threatening environment and allowed the evaluation of how participants' inhibitory control manifest in this realistic stop-signal task. In order to investigate the participants' brain activities with both high spatial and temporal resolution, simultaneous functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) recordings were acquired. The results demonstrated that both scenarios induced increased activity in the right inferior frontal gyrus (rIFG) and presupplementary motor area (preSMA), which have been linked to response inhibition. Notably, in right temporoparietal junction (rTPJ) we found both higher blood-oxygen-level dependent (BOLD) activation and synchronization of theta-alpha activities (4-12 Hz) in the BFS than in the traditional scenario after the stop signal. The higher activation of rTPJ in the BFS may be related to morality judgments or attentional reorienting. These results provided new insights into the complex brain networks involved in inhibitory control within naturalistic environments. PMID- 27199710 TI - The Brain Is Faster than the Hand in Split-Second Intentions to Respond to an Impending Hazard: A Simulation of Neuroadaptive Automation to Speed Recovery to Perturbation in Flight Attitude. AB - The goal of this research is to test the potential for neuroadaptive automation to improve response speed to a hazardous event by using a brain-computer interface (BCI) to decode perceptual-motor intention. Seven participants underwent four experimental sessions while measuring brain activity with magnetoencephalograpy. The first three sessions were of a simple constrained task in which the participant was to pull back on the control stick to recover from a perturbation in attitude in one condition and to passively observe the perturbation in the other condition. The fourth session consisted of having to recover from a perturbation in attitude while piloting the plane through the Grand Canyon constantly maneuvering to track over the river below. Independent component analysis was used on the first two sessions to extract artifacts and find an event related component associated with the onset of the perturbation. These two sessions were used to train a decoder to classify trials in which the participant recovered from the perturbation (motor intention) vs. just passively viewing the perturbation. The BCI-decoder was tested on the third session of the same simple task and found to be able to significantly distinguish motor intention trials from passive viewing trials (mean = 69.8%). The same BCI-decoder was then used to test the fourth session on the complex task. The BCI-decoder significantly classified perturbation from no perturbation trials (73.3%) with a significant time savings of 72.3 ms (Original response time of 425.0-352.7 ms for BCI-decoder). The BCI-decoder model of the best subject was shown to generalize for both performance and time savings to the other subjects. The results of our off-line open loop simulation demonstrate that BCI based neuroadaptive automation has the potential to decode motor intention faster than manual control in response to a hazardous perturbation in flight attitude while ignoring ongoing motor and visual induced activity related to piloting the airplane. PMID- 27199711 TI - More Than Meets the Eye: The Merging of Perceptual and Conceptual Knowledge in the Anterior Temporal Face Area. AB - An emerging body of research has supported the existence of a small face sensitive region in the ventral anterior temporal lobe (ATL), referred to here as the "anterior temporal face area". The contribution of this region in the greater face-processing network remains poorly understood. The goal of the present study was to test the relative sensitivity of this region to perceptual as well as conceptual information about people and objects. We contrasted the sensitivity of this region to that of two highly-studied face-sensitive regions, the fusiform face area (FFA) and the occipital face area (OFA), as well as a control region in early visual cortex (EVC). Our findings revealed that multivoxel activity patterns in the anterior temporal face area contain information about facial identity, as well as conceptual attributes such as one's occupation. The sensitivity of this region to the conceptual attributes of people was greater than that of posterior face processing regions. In addition, the anterior temporal face area overlaps with voxels that contain information about the conceptual attributes of concrete objects, supporting a generalized role of the ventral ATLs in the identification and conceptual processing of multiple stimulus classes. PMID- 27199712 TI - Decreased Cerebellar-Orbitofrontal Connectivity Correlates with Stuttering Severity: Whole-Brain Functional and Structural Connectivity Associations with Persistent Developmental Stuttering. AB - Persistent developmental stuttering is characterized by speech production disfluency and affects 1% of adults. The degree of impairment varies widely across individuals and the neural mechanisms underlying the disorder and this variability remain poorly understood. Here we elucidate compensatory mechanisms related to this variability in impairment using whole-brain functional and white matter connectivity analyses in persistent developmental stuttering. We found that people who stutter had stronger functional connectivity between cerebellum and thalamus than people with fluent speech, while stutterers with the least severe symptoms had greater functional connectivity between left cerebellum and left orbitofrontal cortex (OFC). Additionally, people who stutter had decreased functional and white matter connectivity among the perisylvian auditory, motor, and speech planning regions compared to typical speakers, but greater functional connectivity between the right basal ganglia and bilateral temporal auditory regions. Structurally, disfluency ratings were negatively correlated with white matter connections to left perisylvian regions and to the brain stem. Overall, we found increased connectivity among subcortical and reward network structures in people who stutter compared to controls. These connections were negatively correlated with stuttering severity, suggesting the involvement of cerebellum and OFC may underlie successful compensatory mechanisms by more fluent stutterers. PMID- 27199714 TI - Hybrid ICA-Regression: Automatic Identification and Removal of Ocular Artifacts from Electroencephalographic Signals. AB - Electroencephalography (EEG) is a portable brain-imaging technique with the advantage of high-temporal resolution that can be used to record electrical activity of the brain. However, it is difficult to analyze EEG signals due to the contamination of ocular artifacts, and which potentially results in misleading conclusions. Also, it is a proven fact that the contamination of ocular artifacts cause to reduce the classification accuracy of a brain-computer interface (BCI). It is therefore very important to remove/reduce these artifacts before the analysis of EEG signals for applications like BCI. In this paper, a hybrid framework that combines independent component analysis (ICA), regression and high order statistics has been proposed to identify and eliminate artifactual activities from EEG data. We used simulated, experimental and standard EEG signals to evaluate and analyze the effectiveness of the proposed method. Results demonstrate that the proposed method can effectively remove ocular artifacts as well as it can preserve the neuronal signals present in EEG data. A comparison with four methods from literature namely ICA, regression analysis, wavelet-ICA (wICA), and regression-ICA (REGICA) confirms the significantly enhanced performance and effectiveness of the proposed method for removal of ocular activities from EEG, in terms of lower mean square error and mean absolute error values and higher mutual information between reconstructed and original EEG. PMID- 27199713 TI - Oscillatory Brain Dynamics during Sentence Reading: A Fixation-Related Spectral Perturbation Analysis. AB - The present study investigated oscillatory brain dynamics during self-paced sentence-level processing. Participants read fully correct sentences, sentences containing a semantic violation and "sentences" in which the order of the words was randomized. At the target word level, fixations on semantically unrelated words elicited a lower-beta band (13-18 Hz) desynchronization. At the sentence level, gamma power (31-55 Hz) increased linearly for syntactically correct sentences, but not when the order of the words was randomized. In the 300-900 ms time window after sentence onsets, theta power (4-7 Hz) was greater for syntactically correct sentences as compared to sentences where no syntactic structure was preserved (random words condition). We interpret our results as conforming with a recently formulated predictive-coding framework for oscillatory neural dynamics during sentence-level language comprehension. Additionally, we discuss how our results relate to previous findings with serial visual presentation vs. self-paced reading. PMID- 27199715 TI - Informal Face-to-Face Interaction Improves Mood State Reflected in Prefrontal Cortex Activity. AB - Recent progress with wearable sensors has enabled researchers to capture face-to face interactions quantitatively and given great insight into human dynamics. One attractive field for applying such sensors is the workplace, where the relationship between the face-to-face behaviors of employees and the productivity of the organization has been investigated. One interesting result of previous studies showed that informal face-to-face interaction among employees, captured by wearable sensors that the employees wore, significantly affects their performance. However, the mechanism behind this relationship has not yet been adequately explained, though experiences at the job scene might qualitatively support the finding. We hypothesized that informal face-to-face interaction improves mood state, which in turn affects the task performance. To test this hypothesis, we evaluated the change of mood state before and after break time for two groups of participants, one that spent their breaks alone and one that spent them with other participants, by administering questionnaires and taking brain activity measurements. Recent neuroimaging studies have suggested a significant relationship between mood state and brain activity. Here, we show that face-to face interaction during breaks significantly improved mood state, which was measured by Profiles of Mood States (POMS). We also observed that the verbal working memory (WM) task performance of participants who did not have face-to face interaction during breaks decreased significantly. In this paper, we discuss how the change of mood state was evidenced in the prefrontal cortex (PFC) activity accompanied by WM tasks measured by near-infrared spectroscopy (NIRS). PMID- 27199716 TI - Mapping Smoking Addiction Using Effective Connectivity Analysis. AB - Prefrontal and parietal cortex, including the default mode network (DMN; medial prefrontal cortex (mPFC), and posterior cingulate cortex, PCC), have been implicated in addiction. Nonetheless, it remains unclear which brain regions play a crucial role in smoking addiction and the relationship among these regions. Since functional connectivity only measures correlations, addiction-related changes in effective connectivity (directed information flow) among these distributed brain regions remain largely unknown. Here we applied spectral dynamic causal modeling (spDCM) to resting state fMRI to characterize changes in effective connectivity among core regions in smoking addiction. Compared to nonsmokers, smokers had reduced effective connectivity from PCC to mPFC and from RIPL to mPFC, a higher self-inhibition within PCC and a reduction in the amplitude of endogenous neuronal fluctuations driving the mPFC. These results indicate that spDCM can differentiate the functional architectures between the two groups, and may provide insight into the brain mechanisms underlying smoking addiction. Our results also suggest that future brain-based prevention and intervention in addiction should consider the amelioration of mPFC-PCC-IPL circuits. PMID- 27199717 TI - Commentary: Episodic Memory Retrieval Functionally Relies on Very Rapid Reactivation of Sensory Information. PMID- 27199718 TI - Pantomime-Grasping: Advance Knowledge of Haptic Feedback Availability Supports an Absolute Visuo-Haptic Calibration. AB - An emerging issue in movement neurosciences is whether haptic feedback influences the nature of the information supporting a simulated grasping response (i.e., pantomime-grasping). In particular, recent work by our group contrasted pantomime grasping responses performed with (i.e., PH+ trials) and without (i.e., PH- trials) terminal haptic feedback in separate blocks of trials. Results showed that PH- trials were mediated via relative visual information. In contrast, PH+ trials showed evidence of an absolute visuo-haptic calibration-a finding attributed to an error signal derived from a comparison between expected and actual haptic feedback (i.e., an internal forward model). The present study examined whether advanced knowledge of haptic feedback availability influences the aforementioned calibration process. To that end, PH- and PH+ trials were completed in separate blocks (i.e., the feedback schedule used in our group's previous study) and a block wherein PH- and PH+ trials were randomly interleaved on a trial-by-trial basis (i.e., random feedback schedule). In other words, the random feedback schedule precluded participants from predicting whether haptic feedback would be available at the movement goal location. We computed just noticeable-difference (JND) values to determine whether responses adhered to, or violated, the relative psychophysical principles of Weber's law. Results for the blocked feedback schedule replicated our group's previous work, whereas in the random feedback schedule PH- and PH+ trials were supported via relative visual information. Accordingly, we propose that a priori knowledge of haptic feedback is necessary to support an absolute visuo-haptic calibration. Moreover, our results demonstrate that the presence and expectancy of haptic feedback is an important consideration in contrasting the behavioral and neural properties of natural and simulated grasping. PMID- 27199719 TI - Decreased Modulation of EEG Oscillations in High-Functioning Autism during a Motor Control Task. AB - Autism spectrum disorders (ASD) are thought to result in part from altered cortical excitatory-inhibitory balance; this pathophysiology may impact the generation of oscillations on electroencephalogram (EEG). We investigated premotor-parietal cortical physiology associated with praxis, which has strong theoretical and empirical associations with ASD symptomatology. Twenty five children with high-functioning ASD (HFA) and 33 controls performed a praxis task involving the pantomiming of tool use, while EEG was recorded. We assessed task related modulation of signal power in alpha and beta frequency bands. Compared with controls, subjects with HFA showed 27% less left central (motor/premotor) beta (18-22 Hz) event-related desynchronization (ERD; p = 0.030), as well as 24% less left parietal alpha (7-13 Hz) ERD (p = 0.046). Within the HFA group, blunting of central ERD attenuation was associated with impairments in clinical measures of praxis imitation (r = -0.4; p = 0.04) and increased autism severity (r = 0.48; p = 0.016). The modulation of central beta activity is associated, among other things, with motor imagery, which may be necessary for imitation. Impaired imitation has been associated with core features of ASD. Altered modulation of oscillatory activity may be mechanistically involved in those aspects of motor network function that relate to the core symptoms of ASD. PMID- 27199720 TI - Electrocorticographic Activation within Human Auditory Cortex during Dialog-Based Language and Cognitive Testing. AB - Current models of cortical speech and language processing include multiple regions within the temporal lobe of both hemispheres. Human communication, by necessity, involves complex interactions between regions subserving speech and language processing with those involved in more general cognitive functions. To assess these interactions, we utilized an ecologically salient conversation-based approach. This approach mandates that we first clarify activity patterns at the earliest stages of cortical speech processing. Therefore, we examined high gamma (70-150 Hz) responses within the electrocorticogram (ECoG) recorded simultaneously from Heschl's gyrus (HG) and lateral surface of the superior temporal gyrus (STG). Subjects were neurosurgical patients undergoing evaluation for treatment of medically intractable epilepsy. They performed an expanded version of the Mini-mental state examination (MMSE), which included additional spelling, naming, and memory-based tasks. ECoG was recorded from HG and the STG using multicontact depth and subdural electrode arrays, respectively. Differences in high gamma activity during listening to the interviewer and the subject's self generated verbal responses were quantified for each recording site and across sites within HG and STG. The expanded MMSE produced widespread activation in auditory cortex of both hemispheres. No significant difference was found between activity during listening to the interviewer's questions and the subject's answers in posteromedial HG (auditory core cortex). A different pattern was observed throughout anterolateral HG and posterior and middle portions of lateral STG (non-core auditory cortical areas), where activity was significantly greater during listening compared to speaking. No systematic task-specific differences in the degree of suppression during speaking relative to listening were found in posterior and middle STG. Individual sites could, however, exhibit task-related variability in the degree of suppression during speaking compared to listening. The current study demonstrates that ECoG recordings can be acquired in time efficient dialog-based paradigms, permitting examination of language and cognition in an ecologically salient manner. The results obtained from auditory cortex serve as a foundation for future studies addressing patterns of activity beyond auditory cortex that subserve human communication. PMID- 27199721 TI - Increased Adaptation Rates and Reduction in Trial-by-Trial Variability in Subjects with Cerebral Palsy Following a Multi-session Locomotor Adaptation Training. AB - Cerebral Palsy (CP) results from an insult to the developing brain and is associated with deficits in locomotor and manual skills and in sensorimotor adaptation. We hypothesized that the poor sensorimotor adaptation in persons with CP is related to their high execution variability and does not reflect a general impairment in adaptation learning. We studied the interaction between performance variability and adaptation deficits using a multi-session locomotor adaptation design in persons with CP. Six adolescents with diplegic CP were exposed, during a period of 15 weeks, to a repeated split-belt treadmill perturbation spread over 30 sessions and were tested again 6 months after the end of training. Compared to age-matched healthy controls, subjects with CP showed poor adaptation and high execution variability in the first exposure to the perturbation. Following training they showed marked reduction in execution variability and an increase in learning rates. The reduction in variability and the improvement in adaptation were highly correlated in the CP group and were retained 6 months after training. Interestingly, despite reducing their variability in the washout phase, subjects with CP did not improve learning rates during washout phases that were introduced only four times during the experiment. Our results suggest that locomotor adaptation in subjects with CP is related to their execution variability. Nevertheless, while variability reduction is generalized to other locomotor contexts, the development of savings requires both reduction in execution variability and multiple exposures to the perturbation. PMID- 27199722 TI - Neural Adaptations Associated with Interlimb Transfer in a Ballistic Wrist Flexion Task. AB - Cross education is the process whereby training of one limb gives rise to increases in the subsequent performance of its opposite counterpart. The execution of many unilateral tasks is associated with increased excitability of corticospinal projections from primary motor cortex (M1) to the opposite limb. It has been proposed that these effects are causally related. Our aim was to establish whether changes in corticospinal excitability (CSE) arising from prior training of the opposite limb determine levels of interlimb transfer. We used three vision conditions shown previously to modulate the excitability of corticospinal projections to the inactive (right) limb during wrist flexion movements performed by the training (left) limb. These were: (1) mirrored visual feedback of the training limb; (2) no visual feedback of either limb; and (3) visual feedback of the inactive limb. Training comprised 300 discrete, ballistic wrist flexion movements executed as rapidly as possible. Performance of the right limb on the same task was assessed prior to, at the mid point of, and following left limb training. There was no evidence that variations in the excitability of corticospinal projections (assessed by transcranial magnetic stimulation (TMS)) to the inactive limb were associated with, or predictive of, the extent of interlimb transfer that was expressed. There were however associations between alterations in muscle activation dynamics observed for the untrained limb, and the degree of positive transfer that arose from training of the opposite limb. The results suggest that the acute adaptations that mediate the bilateral performance gains realized through unilateral practice of this ballistic wrist flexion task are mediated by neural elements other than those within M1 that are recruited at rest by single-pulse TMS. PMID- 27199723 TI - Video Game Training Enhances Visuospatial Working Memory and Episodic Memory in Older Adults. AB - In this longitudinal intervention study with experimental and control groups, we investigated the effects of video game training on the visuospatial working memory (WM) and episodic memory of healthy older adults. Participants were 19 volunteer older adults, who received 15 1-h video game training sessions with a series of video games selected from a commercial package (Lumosity), and a control group of 20 healthy older adults. The results showed that the performance of the trainees improved significantly in all the practiced video games. Most importantly, we found significant enhancements after training in the trained group and no change in the control group in two computerized tasks designed to assess visuospatial WM, namely the Corsi blocks task and the Jigsaw puzzle task. The episodic memory and short-term memory of the trainees also improved. Gains in some WM and episodic memory tasks were maintained during a 3-month follow-up period. These results suggest that the aging brain still retains some degree of plasticity, and that video game training might be an effective intervention tool to improve WM and other cognitive functions in older adults. PMID- 27199724 TI - Outcome Uncertainty and Brain Activity Aberrance in the Insula and Anterior Cingulate Cortex Are Associated with Dysfunctional Impulsivity in Borderline Personality Disorder. AB - Uncertainty is recognized as an important component in distress, which may elicit impulsive behavior in patients with borderline personality disorder (BPD). These patients are known to be both impulsive and distress intolerant. The present study explored the connection between outcome uncertainty and impulsivity in BPD. The prediction was that cue primes, which provide incomplete information of subsequent target stimuli, led BPD patients to overrate the predictive value of these cues in order to reduce distress related to outcome uncertainty. This would yield dysfunctional impulsive behavior detected as commission errors to incorrectly primed targets. We hypothesized that dysfunctional impulsivity would be accompanied by aberrant brain activity in the right insula and anterior cingulate cortex (ACC), previously described to be involved in uncertainty processing, attention-/cognitive control and BPD pathology. 14 female BPD patients and 14 healthy matched controls (HCs) for comparison completed a Posner task during fMRI at 3T. The task was modified to limit the effect of spatial orientation and enhance the effect of conscious expectations. Brain activity was monitored in the priming phase where the effects of cue primes and neutral primes were compared. As predicted, the BPD group made significantly more commission errors to incorrectly primed targets than HCs. Also, the patients had faster reaction times to correctly primed targets relative to targets preceded by neutral primes. The BPD group had decreased activity in the right mid insula and increased activity in bilateral dorsal ACC during cue primes. The results indicate that strong expectations induced by cue primes led to reduced uncertainty, increased response readiness, and ultimately, dysfunctional impulsivity in BPD patients. We suggest that outcome uncertainty may be an important component in distress related impulsivity in BPD. PMID- 27199726 TI - Simulating the Effect of Reinforcement Learning on Neuronal Synchrony and Periodicity in the Striatum. AB - The study of rhythms and oscillations in the brain is gaining attention. While it is unclear exactly what the role of oscillation, synchrony, and rhythm is, it appears increasingly likely that synchrony is related to normal and abnormal brain states and possibly cognition. In this article, we explore the relationship between basal ganglia (BG) synchrony and reinforcement learning. We simulate a biologically-realistic model of the striatum initially proposed by Ponzi and Wickens (2010) and enhance the model by adding plastic cortico-BG synapses that can be modified using reinforcement learning. The effect of reinforcement learning on striatal rhythmic activity is then explored, and disrupted using simulated deep brain stimulation (DBS). The stimulator injects current in the brain structure to which it is attached, which affects neuronal synchrony. The results show that training the model without DBS yields a high accuracy in the learning task and reduced the number of active neurons in the striatum, along with an increased firing periodicity and a decreased firing synchrony between neurons in the same assembly. In addition, a spectral decomposition shows a stronger signal for correct trials than incorrect trials in high frequency bands. If the DBS is ON during the training phase, but not the test phase, the amount of learning in the model is reduced, along with firing periodicity. Similar to when the DBS is OFF, spectral decomposition shows a stronger signal for correct trials than for incorrect trials in high frequency domains, but this phenoemenon happens in higher frequency bands than when the DBS is OFF. Synchrony between the neurons is not affected. Finally, the results show that turning the DBS ON at test increases both firing periodicity and striatal synchrony, and spectral decomposition of the signal show that neural activity synchronizes with the DBS fundamental frequency (and its harmonics). Turning the DBS ON during the test phase results in chance performance regardless of whether the DBS was ON or OFF during training. We conclude that reinforcement learning is related to firing periodicity, and a stronger signal for correct trials when compared to incorrect trials in high frequency bands. PMID- 27199725 TI - Computational Analysis of the Hypothalamic Control of Food Intake. AB - Food-intake control is mediated by a heterogeneous network of different neural subtypes, distributed over various hypothalamic nuclei and other brain structures, in which each subtype can release more than one neurotransmitter or neurohormone. The complexity of the interactions of these subtypes poses a challenge to understanding their specific contributions to food-intake control, and apparent consistencies in the dataset can be contradicted by new findings. For example, the growing consensus that arcuate nucleus neurons expressing Agouti related peptide (AgRP neurons) promote feeding, while those expressing pro opiomelanocortin (POMC neurons) suppress feeding, is contradicted by findings that low AgRP neuron activity and high POMC neuron activity can be associated with high levels of food intake. Similarly, the growing consensus that GABAergic neurons in the lateral hypothalamus suppress feeding is contradicted by findings suggesting the opposite. Yet the complexity of the food-intake control network admits many different network behaviors. It is possible that anomalous associations between the responses of certain neural subtypes and feeding are actually consistent with known interactions, but their effect on feeding depends on the responses of the other neural subtypes in the network. We explored this possibility through computational analysis. We made a computer model of the interactions between the hypothalamic and other neural subtypes known to be involved in food-intake control, and optimized its parameters so that model behavior matched observed behavior over an extensive test battery. We then used specialized computational techniques to search the entire model state space, where each state represents a different configuration of the responses of the units (model neural subtypes) in the network. We found that the anomalous associations between the responses of certain hypothalamic neural subtypes and feeding are actually consistent with the known structure of the food-intake control network, and we could specify the ways in which the anomalous configurations differed from the expected ones. By analyzing the temporal relationships between different states we identified the conditions under which the anomalous associations can occur, and these stand as model predictions. PMID- 27199727 TI - A Brain Signature to Differentiate Acute and Chronic Pain in Rats. AB - The transition from acute pain to chronic pain entails considerable changes of patients at multiple levels of the nervous system and in psychological states. An accurate differentiation between acute and chronic pain is essential in pain management as it may help optimize analgesic treatments according to the pain state of patients. Given that acute and chronic pain could modulate brain states in different ways and that brain states could greatly shape the neural processing of external inputs, we hypothesized that acute and chronic pain would show differential effects on cortical responses to non-nociceptive sensory information. Here by analyzing auditory-evoked potentials (AEPs) to pure tones in rats with acute or chronic pain, we found opposite influences of acute and chronic pain on cortical responses to auditory inputs. In particular, compared to no-pain controls, the N100 wave of rat AEPs was significantly enhanced in rats with acute pain but significantly reduced in rats with chronic pain, indicating that acute pain facilitated cortical processing of auditory information while chronic pain exerted an inhibitory effect. These findings could be justified by the fact that individuals suffering from acute or chronic pain would have different vigilance states, i.e., the vigilance level to external sensory stimuli would be increased with acute pain, but decreased with chronic pain. Therefore, this auditory response holds promise of being a brain signature to differentiate acute and chronic pain. Instead of investigating the pain system per se, the study of pain-induced influences on cortical processing of non-nocicpetive sensory information might represent a potential strategy to monitor the progress of pain chronification in clinical applications. PMID- 27199729 TI - An Intracranial Electroencephalography (iEEG) Brain Function Mapping Tool with an Application to Epilepsy Surgery Evaluation. AB - OBJECTS: Before epilepsy surgeries, intracranial electroencephalography (iEEG) is often employed in function mapping and epileptogenic foci localization. Although the implanted electrodes provide crucial information for epileptogenic zone resection, a convenient clinical tool for electrode position registration and Brain Function Mapping (BFM) visualization is still lacking. In this study, we developed a BFM Tool, which facilitates electrode position registration and BFM visualization, with an application to epilepsy surgeries. METHODS: The BFM Tool mainly utilizes electrode location registration and function mapping based on pre defined brain models from other software. In addition, the electrode node and mapping properties, such as the node size/color, edge color/thickness, mapping method, can be adjusted easily using the setting panel. Moreover, users may manually import/export location and connectivity data to generate figures for further application. The role of this software is demonstrated by a clinical study of language area localization. RESULTS: The BFM Tool helps clinical doctors and researchers visualize implanted electrodes and brain functions in an easy, quick and flexible manner. CONCLUSIONS: Our tool provides convenient electrode registration, easy brain function visualization, and has good performance. It is clinical-oriented and is easy to deploy and use. The BFM tool is suitable for epilepsy and other clinical iEEG applications. PMID- 27199728 TI - Topography of Synchronization of Somatosensory Evoked Potentials Elicited by Stimulation of the Sciatic Nerve in Rat. AB - PURPOSE: Traditionally, the topography of somatosensory evoked potentials (SEPs) is generated based on amplitude and latency. However, this operation focuses on the physical morphology and field potential-power, so it suffers from difficulties in performing identification in an objective manner. In this study, measurement of the synchronization of SEPs is proposed as a method to explore brain functional networks as well as the plasticity after peripheral nerve injury. METHOD: SEPs elicited by unilateral sciatic nerve stimulation in twelve adult male Sprague-Dawley (SD) rats in the normal group were compared with SEPs evoked after unilateral sciatic nerve hemisection in four peripheral nerve injured SD rats. The characterization of synchronized networks from SEPs was conducted using equal-time correlation, correlation matrix analysis, and comparison to randomized surrogate data. Eigenvalues of the correlation matrix were used to identify the clusters of functionally synchronized neuronal activity, and the participation index (PI) was calculated to indicate the involvement of each channel in the cluster. The PI value at the knee point of the PI histogram was used as a threshold to demarcate the cortical boundary. RESULTS: Ten out of the twelve normal rats showed only one synchronized brain network. The remaining two normal rats showed one strong and one weak network. In the peripheral nerve injured group, only one synchronized brain network was found in each rat. In the normal group, all network shapes appear regular and the network is largely contained in the posterior cortex. In the injured group, the network shapes appear irregular, the network extends anteriorly and posteriorly, and the network area is significantly larger. There are considerable individual variations in the shape and location of the network after peripheral nerve injury. CONCLUSION: The proposed method can detect functional brain networks. Compared to the results of the traditional SEP-morphology-based analysis method, the synchronized functional network area is much larger. Furthermore, the proposed method can also characterize the rapid cortical plasticity after a peripheral nerve is acutely injured. PMID- 27199731 TI - Emotional Egocentricity Bias Across the Life-Span. AB - In our daily lives, we often have to quickly estimate the emotions of our conspecifics in order to have successful social interactions. While this estimation process seems quite easy when we are ourselves in a neutral or equivalent emotional state, it has recently been shown that in case of incongruent emotional states between ourselves and the others, our judgments can be biased. This phenomenon, introduced to the literature with the term Emotional Egocentricity Bias (EEB), has been found to occur in young adults and, to a greater extent, in children. However, how the EEB changes across the life-span from adolescence to old age has been largely unexplored. In this study, we recruited 114 female participants subdivided in four cohorts (adolescents, young adults, middle-aged adults, older adults) to examine EEB age-related changes. Participants were administered with a recently developed paradigm which, by making use of visuo-tactile stimulation that elicits conflicting feelings in paired participants, allows the valid and reliable exploration of the EEB. Results highlighted a U-shape relation between age and EEB, revealing enhanced emotional egocentricity in adolescents and older adults compared to young and middle-aged adults. These results are in line with the neuroscientific literature which has recently shown that overcoming the EEB is associated with a greater activation of a portion of the parietal lobe, namely the right Supramarginal Gyrus (rSMG). This is an area that reaches full maturation by the end of adolescence and goes through an early decay. Thus, the age-related changes of the EEB could be possibly due to the life-span development of the rSMG. This study is the first one to show the quadratic relation between age and the EEB and set a milestone for further research exploring the neural correlates of the life-span development of the EEB. Future studies are needed in order to generalize these results to the male population and to explore gender differences related to the aging of socio- emotional processes. PMID- 27199732 TI - Cortical Modulation of Motor Control Biofeedback among the Elderly with High Fall Risk during a Posture Perturbation Task with Augmented Reality. AB - The cerebral cortex provides sensorimotor integration and coordination during motor control of daily functional activities. Power spectrum density based on electroencephalography (EEG) has been employed as an approach that allows an investigation of the spatial-temporal characteristics of neuromuscular modulation; however, the biofeedback mechanism associated with cortical activation during motor control remains unclear among elderly individuals. Thirty one community-dwelling elderly participants were divided into low fall-risk potential (LF) and high fall-risk potential (HF) groups based upon the results obtained from a receiver operating characteristic analysis of the ellipse area of the center of pressure. Electroencephalography (EEG) was performed while the participants stood on a 6-degree-of-freedom Stewart platform, which generated continuous perturbations and done either with or without the virtual reality scene. The present study showed that when there was visual stimulation and poor somatosensory coordination, a higher level of cortical response was activated in order to keep postural balance. The elderly participants in the LF group demonstrated a significant and strong correlation between postural-related cortical regions; however, the elderly individuals in the HF group did not show such a relationship. Moreover, we were able to clarify the roles of various brainwave bands functioning in motor control. Specifically, the gamma and beta bands in the parietal-occipital region facilitate the high-level cortical modulation and sensorimotor integration, whereas the theta band in the frontal central region is responsible for mediating error detection during perceptual motor tasks. Finally, the alpha band is associated with processing visual challenges in the occipital lobe.With a variety of motor control demands, increment in brainwave band coordination is required to maintain postural stability. These investigations shed light on the cortical modulation of motor control among elderly participants with varying fall-risk potentials. The results suggest that, although elderly adults may be without neurological deficits, inefficient central modulation during challenging postural conditions could be an internal factor that contributes to the risk of fall. Furthermore, training that helps to improve coordinated sensorimotor integration may be a useful approach to reduce the risk of fall among elderly populations or when patients suffer from neurological deficits. PMID- 27199730 TI - Sumoylation in Synaptic Function and Dysfunction. AB - Sumoylation has recently emerged as a key post-translational modification involved in many, if not all, biological processes. Small Ubiquitin-like Modifier (SUMO) polypeptides are covalently attached to specific lysine residues of target proteins through a dedicated enzymatic pathway. Disruption of the SUMO enzymatic pathway in the developing brain leads to lethality indicating that this process exerts a central role during embryonic and post-natal development. However, little is still known regarding how this highly dynamic protein modification is regulated in the mammalian brain despite an increasing number of data implicating sumoylated substrates in synapse formation, synaptic communication and plasticity. The aim of this review is therefore to briefly describe the enzymatic SUMO pathway and to give an overview of our current knowledge on the function and dysfunction of protein sumoylation at the mammalian synapse. PMID- 27199734 TI - Cognitive Reserve in Dementia: Implications for Cognitive Training. AB - Cognitive reserve (CR) is a potential mechanism to cope with brain damage. The aim of this study was to evaluate the effect of CR on a cognitive training (CT) in a group of patients with dementia. Eighty six participants with mild to moderate dementia were identified by their level of CR quantified by the CR Index questionnaire (CRIq) and underwent a cycle of CT. A global measure of cognition mini mental state examination (MMSE) was obtained before (T0) and after (T1) the training. Multiple linear regression analyses highlighted CR as a significant factor able to predict changes in cognitive performance after the CT. In particular, patients with lower CR benefited from a CT program more than those with high CR. These data show that CR can modulate the outcome of a CT program and that it should be considered as a predictive factor of neuropsychological rehabilitation training efficacy in people with dementia. PMID- 27199735 TI - Atomic Force Microscopy Protocol for Measurement of Membrane Plasticity and Extracellular Interactions in Single Neurons in Epilepsy. AB - Physiological interactions between extracellular matrix (ECM) proteins and membrane integrin receptors play a crucial role in neuroplasticity in the hippocampus, a key region involved in epilepsy. The atomic force microscopy (AFM) is a cutting-edge technique to study structural and functional measurements at nanometer resolution between the AFM probe and cell surface under liquid. AFM has been incrementally employed in living cells including the nervous system. AFM is a unique technique that directly measures functional information at a nanoscale resolution. In addition to its ability to acquire detailed 3D imaging, the AFM probe permits quantitative measurements on the structure and function of the intracellular components such as cytoskeleton, adhesion force and binding probability between membrane receptors and ligands coated in the AFM probe, as well as the cell stiffness. Here we describe an optimized AFM protocol and its application for analysis of membrane plasticity and mechanical dynamics of individual hippocampus neurons in mice with chronic epilepsy. The unbinding force and binding probability between ECM, fibronectin-coated AFM probe and membrane integrin were strikingly lower in dentate gyrus granule cells in epilepsy. Cell elasticity, which represents changes in cytoskeletal reorganization, was significantly increased in epilepsy. The fibronectin-integrin binding probability was prevented by anti-alpha5beta1 integrin. Thus, AFM is a unique nanotechnique that allows progressive functional changes in neuronal membrane plasticity and mechanotransduction in epilepsy and related brain disorders. PMID- 27199733 TI - Glial Modulation by N-acylethanolamides in Brain Injury and Neurodegeneration. AB - Neuroinflammation involves the activation of glial cells and represents a key element in normal aging and pathophysiology of brain damage. N-acylethanolamides (NAEs), naturally occurring amides, are known for their pro-homeostatic effects. An increase in NAEs has been reported in vivo and in vitro in the aging brain and in brain injury. Treatment with NAEs may promote neuroprotection and exert anti inflammatory actions via PPARalpha activation and/or by counteracting gliosis. This review aims to provide an overview of endogenous and exogenous properties of NAEs in neuroinflammation and to discuss their interaction with glial cells. PMID- 27199736 TI - Implicit Motor Sequence Learning and Working Memory Performance Changes Across the Adult Life Span. AB - Although implicit motor sequence learning is rather well understood in young adults, effects of aging on this kind of learning are controversial. There is first evidence that working memory (WM) might play a role in implicit motor sequence learning in young adults as well as in adults above the age of 65. However, the knowledge about the development of these processes across the adult life span is rather limited. As the average age of our population continues to rise, a better understanding of age-related changes in motor sequence learning and potentially mediating cognitive processes takes on increasing significance. Therefore, we investigated aging effects on implicit motor sequence learning and WM. Sixty adults (18-71 years) completed verbal and visuospatial n-back tasks and were trained on a serial reaction time task (SRTT). Randomly varying trials served as control condition. To further assess consolidation indicated by off line improvement and reduced susceptibility to interference, reaction times (RTs) were determined 1 h after initial learning. Young and older but not middle-aged adults showed motor sequence learning. Nine out of 20 older adults (compared to one young/one middle-aged) exhibited some evidence of sequence awareness. After 1 h, young and middle-aged adults showed off-line improvement. However, RT facilitation was not specific to sequence trials. Importantly, susceptibility to interference was reduced in young and older adults indicating the occurrence of consolidation. Although WM performance declined in older participants when load was high, it was not significantly related to sequence learning. The data reveal a decline in motor sequence learning in middle-aged but not in older adults. The use of explicit learning strategies in older adults might account for the latter result. PMID- 27199737 TI - Age-Related Declines in Early Sensory Memory: Identification of Rapid Auditory and Visual Stimulus Sequences. AB - Age-related temporal-processing declines of rapidly presented sequences may involve contributions of sensory memory. This study investigated recall for rapidly presented auditory (vowel) and visual (letter) sequences presented at six different stimulus onset asynchronies (SOA) that spanned threshold SOAs for sequence identification. Younger, middle-aged, and older adults participated in all tasks. Results were investigated at both equivalent performance levels (i.e., SOA threshold) and at identical physical stimulus values (i.e., SOAs). For four item sequences, results demonstrated best performance for the first and last items in the auditory sequences, but only the first item for visual sequences. For two-item sequences, adults identified the second vowel or letter significantly better than the first. Overall, when temporal-order performance was equated for each individual by testing at SOA thresholds, recall accuracy for each position across the age groups was highly similar. These results suggest that modality-specific processing declines of older adults primarily determine temporal-order performance for rapid sequences. However, there is some evidence for a second amodal processing decline in older adults related to early sensory memory for final items in a sequence. This selective deficit was observed particularly for longer sequence lengths and was not accounted for by temporal masking. PMID- 27199738 TI - Early Signs of Pathological Cognitive Aging in Mice Lacking High-Affinity Nicotinic Receptors. AB - In order to address pathological cognitive decline effectively, it is critical to adopt early preventive measures in individuals considered at risk. It is therefore essential to develop approaches that identify such individuals before the onset of irreversible dementia. A deficient cholinergic system has been consistently implicated as one of the main factors associated with a heightened vulnerability to the aging process. In the present study we used mice lacking high affinity nicotinic receptors (beta2-/-), which have been proposed as an animal model of accelerated/premature cognitive aging. Our aim was to identify behavioral signs that could serve as indicators or predictors of impending cognitive decline. We used test batteries in order to assess cognitive functions and additional tasks to investigate spontaneous behaviors, such as species specific activities and exploration/locomotion in a novel environment. Our data confirm the hypothesis that beta2-/- animals exhibit age-related cognitive impairments in spatial learning. In addition, they document age-related deficits in other areas, such as recognition memory, burrowing and nesting building, thereby extending the validity of this animal model for the study of pathological aging. Finally, our data reveal deficits in spontaneous behavior and habituation processes that precede the onset of cognitive decline and could therefore be useful as a non-invasive behavioral screen for identifying animals at risk. To our knowledge, this is the first study to perform an extensive behavioral assessment of an animal model of premature cognitive aging, and our results suggest that beta2-nAChR dependent cognitive deterioration progressively evolves from initial subtle behavioral changes to global dementia due to the combined effect of the neuropathology and aging. PMID- 27199741 TI - Editorial: Role of Stem Cells in Skeletal Muscle Development, Regeneration, Repair, Aging, and Disease. PMID- 27199739 TI - The Biomarkers for Identifying Preclinical Alzheimer's Disease via Structural and Functional Magnetic Resonance Imaging. PMID- 27199742 TI - Editorial: Non-invasive Brain Stimulation and Plasticity Changes in Aging. PMID- 27199740 TI - Cognitively Engaging Activity Is Associated with Greater Cortical and Subcortical Volumes. AB - As the population ages and dementia becomes a growing healthcare concern, it is increasingly important to identify targets for intervention to delay or attenuate cognitive decline. Research has shown that the most successful interventions aim at altering lifestyle factors. Thus, this study examined how involvement in physical, cognitive, and social activity is related to brain structure in older adults. Sixty-five adults (mean age = 71.4 years, standard deviation = 8.9) received the Community Healthy Activities Model Program for Seniors (CHAMPS), a questionnaire that polls everyday activities in which older adults may be involved, and also underwent structural magnetic resonance imaging. Stepwise regression with backward selection was used to predict weekly time spent in either social, cognitive, light physical, or heavy physical activity from the volume of one of the cortical or subcortical regions of interest (corrected by intracranial volume) as well as age, education, and gender as control variables. Regressions revealed that more time spent in cognitive activity was associated with greater volumes of all brain regions studied: total cortex (beta = 0.289, p = 0.014), frontal (beta = 0.276, p = 0.019), parietal (beta = 0.305, p = 0.009), temporal (beta = 0.275, p = 0.020), and occipital (beta = 0.256, p = 0.030) lobes, and thalamus (beta = 0.310, p = 0.010), caudate (beta = 0.233, p = 0.049), hippocampus (beta = 0.286, p = 0.017), and amygdala (beta = 0.336, p = 0.004). These effects remained even after accounting for the positive association between cognitive activity and education. No other activity variable was associated with brain volumes. Results indicate that time spent in cognitively engaging activity is associated with greater cortical and subcortical brain volume. Findings suggest that interventions aimed at increasing levels of cognitive activity may delay cognitive consequences of aging and decrease the risk of developing dementia. PMID- 27199744 TI - Orbitofrontal Cortex and the Early Processing of Visual Novelty in Healthy Aging. AB - Event-related potential (ERP) studies have previously found that scalp topographies of attention-related ERP components show frontal shifts with age, suggesting an increased need for compensatory frontal activity to assist with top down facilitation of attention. However, the precise neural time course of top down attentional control in aging is not clear. In this study, 20 young (mean: 22 years) and 14 older (mean: 64 years) adults completed a three-stimulus visual oddball task while high-density ERPs were acquired. Colorful, novel distracters were presented to engage early visual processing. Relative to young controls, older participants exhibited elevations in occipital early posterior positivity (EPP), approximately 100 ms after viewing colorful distracters. Neural source models for older adults implicated unique patterns of orbitofrontal cortex (OFC; BA 11) activity during early visual novelty processing (100 ms), which was positively correlated with subsequent activations in primary visual cortex (BA 17). Older adult EPP amplitudes and OFC activity were associated with performance on tests of complex attention and executive function. These findings are suggestive of age-related, compensatory neural changes that may driven by a combination of weaker cortical efficiency and increased need for top-down control over attention. Accordingly, enhanced early OFC activity during visual attention may serve as an important indicator of frontal lobe integrity in healthy aging. PMID- 27199743 TI - SUR1 Receptor Interaction with Hesperidin and Linarin Predicts Possible Mechanisms of Action of Valeriana officinalis in Parkinson. AB - Parkinson's disease (PD) is one of the most common neurodegenerative disorders. A theoretical approach of our previous experiments reporting the cytoprotective effects of the Valeriana officinalis compounds extract for PD is suggested. In addiction to considering the PD as a result of mitochondrial metabolic imbalance and oxidative stress, such as in our previous in vitro model of rotenone, in the present manuscript we added a genomic approach to evaluate the possible underlying mechanisms of the effect of the plant extract. Microarray of substantia nigra (SN) genome obtained from Allen Brain Institute was analyzed using gene set enrichment analysis to build a network of hub genes implicated in PD. Proteins transcribed from hub genes and their ligands selected by search ensemble approach algorithm were subjected to molecular docking studies, as well as 20 ns Molecular Dynamics (MD) using a Molecular Mechanic Poison/Boltzman Surface Area (MMPBSA) protocol. Our results bring a new approach to Valeriana officinalis extract, and suggest that hesperidin, and probably linarin are able to relieve effects of oxidative stress during ATP depletion due to its ability to binding SUR1. In addition, the key role of valerenic acid and apigenin is possibly related to prevent cortical hyperexcitation by inducing neuronal cells from SN to release GABA on brain stem. Thus, under hyperexcitability, oxidative stress, asphyxia and/or ATP depletion, Valeriana officinalis may trigger different mechanisms to provide neuronal cell protection. PMID- 27199745 TI - Functional Characterization of Human CYP2C9 Allelic Variants in COS-7 Cells. AB - Variability in activity of CYP2C9, which is involved in the metabolism of approximately 15% of current therapeutic drugs, is an important contributor to interindividual differences in drug response. To evaluate the functional alternations of CYP2C9(*)2, CYP2C9(*)3, CYP2C9(*)8, CYP2C9(*)11 and CYP2C9(*)31, identified in our previous study in Chinese Han population, allelic variants as well as the wild-type CYP2C9 were transiently expressed in COS-7 cells. Kinetic parameters (Km, Vmax, and Clint) for S-warfarin 7-hydroxylation by these recombinant CYP2C9s were determined. Relative to CYP2C9.1, recombinant CYP2C9.3 and CYP2C9.11 exhibited significantly higher Km values, and all allelic variants showed significantly decreased Vmax and Clint values. Among all allelic variants, catalytic activity of CYP2C9.3 and CYP2C9.11 reduced the most (8.2% and 9.8% of Clint ratio, respectively; P < 0.001). These findings should be useful for predicting the phenotype profiles of CYP2C9 in Chinese Han population, comparing the functional results of these alleles accurately, and finally optimizing pharmacotherapy of drug treatment. PMID- 27199746 TI - Triggering of Parkin Mitochondrial Translocation in Mitophagy: Implications for Liver Diseases. AB - A growing body of evidence based on in vitro studies indicates that mitophagy (selective autophagic clearance of damaged mitochondria) is a prosurvival mechanism associated with cellular exposure to various mitochondrial stressors. Very recently, a limited number of publications on animal-based models of alcoholic fatty liver diseases have reported that Parkin-mediated mitophagy may mitigate hepatocyte apoptosis, improve mitochondrial quality and suppress steatosis (lipid accumulation). From this perspective, the authors focus on the mechanisms of Parkin mitochondrial translocation (a key consideration in mitophagy activation) and therapeutic implications of mitophagy in liver disease. DNA repair and other functions of Parkin beyond mitophagy are also briefly discussed. The paper additionally shows original data from the authors' current research indicating enhanced hepatic mitophagy in ethanol-treated rats, which is associated with Parkin mitochondrial translocation triggered by oxidative mitochondrial DNA damage. Natural or pharmaceutical products that may trigger Parkin mitochondrial translocation in hepatocytes and/or suppress repressors of such translocation could be a potential therapeutic target in alcoholic and non alcoholic fatty liver disease. PMID- 27199747 TI - Antidiabetic and Antilipidemic Effect of Musa balbisiana Root Extract: A Potent Agent for Glucose Homeostasis in Streptozotocin-Induced Diabetic Rat. AB - Folklore studies have revealed that Musa balbisiana Colla (MB; Family: Musaceae) has high medicinal properties. The purpose of the present study is to evaluate antihyperglycemic, and antioxidant activity of MB extracts in streptozotocin (STZ) induced diabetic rats. In vitro antioxidant and antidiabetic activity of MB extracts, i.e., root extract (RE), shoot extract and inflorescence extract were determined by using various methods viz 1,-1-diphenyl-2-picrylhydrazyl (DPPH) and a method to assess their possible effect on glucose diffusion across gastrointestinal tract and identify bioactive compound of potent extract. In vivo antilipidemic and antidiabetic activity was evaluated by administrating oral dose of RE for 15 days on STZ- induced diabetic rat. RE showed highest antioxidant activity by scavenging DPPH radical (IC50 32.96 MUg/ml) and inhibit 30% glucose movement in vitro. The methanol extract of root showed the presence of calyx [4] arene category of the compound. Furthermore, RE treated rat revealed a reduction in fasting blood glucose (62.5%), serum total cholesterol (36.2%), triglyceride (54.5%), and low-density lipoprotein (50.94%) after 15 days as compared to STZ treated animal. There was an initiation of regenerative structures of the affected organs after 15 days of RE treatment. Histopathological observations clearly differentiate the structural changes in pancreas, liver, and kidney of STZ and RE treated group. The presence of calyx [4] arene class of compound may be responsible for its antioxidant and antidiabetic properties by absorbing glucose in vivo. PMID- 27199748 TI - Metagenomic Analysis of Antibiotic-Induced Changes in Gut Microbiota in a Pregnant Rat Model. AB - Food and Drug Administration (FDA, USA)-approved category B antibiotics are commonly prescribed to treat infections during pregnancy. The aim of this study was to investigate antibiotic-induced changes in gut microbiota (GM) that occur during pregnancy. The 16S rRNA amplicon deep-sequencing method was used to analyze the effect of category B antibiotics (azithromycin, amoxicillin and cefaclor) on GM during pregnancy using a rat model. The GM composition was substantially modulated by pregnancy and antibiotics administration. Firmicutes, Bacteroidetes, Proteobacteria, Chlamydiae, Actinobacteria, and Cyanobacteria were the dominant phyla. Antibiotic treatment during pregnancy increased the relative abundance of Proteobacteria and reduced Firmicutes. The genera Shigella, Streptococcus, Candidatus Arthromitus, and Helicobacter were significantly (p < 0.05) more abundant during pregnancy. Antibiotics significantly (p < 0.05) reduced the relative abundance of Lactobacillus but increased that of Enterobacter. There was a significant (p < 0.05) decrease in Lactobacillus sp., Lactobacillus gallinarum and Lactobacillus crispatus during pregnancy. Antibiotic treatment reduced bacterial diversity; the lowest number of operational taxonomic units (OTUs) were detected in the cefaclor-treated groups. Antibiotics significantly (p < 0.05) promoted weight gain during pregnancy, and increased relative abundance of Shigella sonnei, Enterococcus hormaechei, and Acinetobacter sp. GM perturbations were accompanied by increases in Proteobacteria abundance and weight gain in pregnancy following antibiotic treatment. PMID- 27199749 TI - Stimulants for the Control of Hedonic Appetite. AB - The focus of this paper is treatment of obesity in relation to the management of hedonic appetite. Obesity is a complex condition which may be potentiated by excessive reward seeking in combination with executive functioning deficits that impair cognitive control of behavior. Stimulant medications address both reward deficiency and enhance motivation, as well as suppressing appetite. They have long been recognized to be effective for treating obesity. However, stimulants can be abused for their euphoric effect. They induce euphoria via the same neural pathway that underlies their therapeutic effect in obesity. For this reason they have generally not been endorsed for use in obesity. Among the stimulants, only phentermine (either alone or in combination with topiramate) and bupropion (which has stimulant-like properties and is used in combination with naltrexone), are approved by the United States Food and Drug Administration (FDA) for obesity, although dexamphetamine and methylpenidate are approved and widely used for treating attention deficit hyperactivity disorder (ADHD) in adults and children. Experience gained over many years in the treatment of ADHD demonstrates that with careful dose titration, stimulants can be used safely. In obesity, improvement in mood and executive functioning could assist with the lifestyle changes necessary for weight control, acting synergistically with appetite suppression. The obesity crisis has reached the stage that strong consideration should be given to adequate utilization of this effective and inexpensive class of drug. PMID- 27199751 TI - Evaluating the Effects of Gamma-Irradiation for Decontamination of Medicinal Cannabis. AB - In several countries with a National medicinal cannabis program, pharmaceutical regulations specify that herbal cannabis products must adhere to strict safety standards regarding microbial contamination. Treatment by gamma irradiation currently seems the only method available to meet these requirements. We evaluated the effects of irradiation treatment of four different cannabis varieties covering different chemical compositions. Samples were compared before and after standard gamma-irradiation treatment by performing quantitative UPLC analysis of major cannabinoids, as well as qualitative GC analysis of full cannabinoid and terpene profiles. In addition, water content and microscopic appearance of the cannabis flowers was evaluated. This study found that treatment did not cause changes in the content of THC and CBD, generally considered as the most important therapeutically active components of medicinal cannabis. Likewise, the water content and the microscopic structure of the dried cannabis flowers were not altered by standard irradiation protocol in the cannabis varieties studied. The effect of gamma-irradiation was limited to a reduction of some terpenes present in the cannabis, but keeping the terpene profile qualitatively the same. Based on the results presented in this report, gamma irradiation of herbal cannabis remains the recommended method of decontamination, at least until other more generally accepted methods have been developed and validated. PMID- 27199750 TI - Cysteine Proteases: Modes of Activation and Future Prospects as Pharmacological Targets. AB - Proteolytic enzymes are crucial for a variety of biological processes in organisms ranging from lower (virus, bacteria, and parasite) to the higher organisms (mammals). Proteases cleave proteins into smaller fragments by catalyzing peptide bonds hydrolysis. Proteases are classified according to their catalytic site, and distributed into four major classes: cysteine proteases, serine proteases, aspartic proteases, and metalloproteases. This review will cover only cysteine proteases, papain family enzymes which are involved in multiple functions such as extracellular matrix turnover, antigen presentation, processing events, digestion, immune invasion, hemoglobin hydrolysis, parasite invasion, parasite egress, and processing surface proteins. Therefore, they are promising drug targets for various diseases. For preventing unwanted digestion, cysteine proteases are synthesized as zymogens, and contain a prodomain (regulatory) and a mature domain (catalytic). The prodomain acts as an endogenous inhibitor of the mature enzyme. For activation of the mature enzyme, removal of the prodomain is necessary and achieved by different modes. The pro-mature domain interaction can be categorized as protein-protein interactions (PPIs) and may be targeted in a range of diseases. Cysteine protease inhibitors are available that can block the active site but no such inhibitor available yet that can be targeted to block the pro-mature domain interactions and prevent it activation. This review specifically highlights the modes of activation (processing) of papain family enzymes, which involve auto-activation, trans-activation and also clarifies the future aspects of targeting PPIs to prevent the activation of cysteine proteases. PMID- 27199752 TI - A Phaseolus vulgaris Extract Reduces Cue-Induced Reinstatement of Chocolate Seeking in Rats. AB - Previous evidence has suggested that treatment with a standardized dry extract of Phaseolus vulgaris reduced intake and operant self-administration of highly palatable foods and fluids in rats and mice. The present study was designed to assess whether such extract was also effective in reducing seeking behavior for a highly hedonic chocolate-flavored beverage, using a "reinstatement" procedure adopted from the drug addiction research field and modeling relapse behavior. Rats were initially trained to lever-respond for the chocolate-flavored beverage under the Fixed Ratio (FR) 10 schedule of reinforcement. Subsequently, rats were exposed to an extinction responding phase, during which lever-responding - being unreinforced - diminished progressively up to extinction. Lever-responding was then powerfully reinstated by the non-contingent presentation of a complex of gustatory, olfactory, auditory, and visual stimuli previously associated to the availability of the chocolate-flavored beverage. Acute, intragastric administration of P. vulgaris dry extract (100 and 500 mg/kg) reduced lever responding by 40-45%, in comparison to vehicle condition. These results indicate the ability of P. vulgaris dry extract to reduce seeking behavior for a highly palatable nourishment in an experimental model of relapse into disordered eating of palatable foods. The unavailability of the chocolate-flavored beverage in the reinstatement session tends to exclude that the observed effect of the P. vulgaris dry extract was secondary to any inhibition of carbohydrate metabolism; conversely, it is the likely consequence on a central action on the rewarding and hedonic properties of food. PMID- 27199753 TI - From Clinical Trials to the Front Line: Vinflunine for Treatment of Urothelial Cell Carcinoma at the National Cancer Institute of Naples. AB - BACKGROUND: The efficacy of Vinflunine, after failure of platinum-based chemotherapy in patients with metastatic or recurrent Transitional Cell Cancer of the Urothelial Tract, TCCU, has been demonstrated in an international, randomized, phase III trial comparing Vinflunine plus Best Supportive Care, BSC, with BSC alone. On the basis of that study vinflunine has been approved by the European Medicine Association, EMA, for treatment of TCCU patients after failure of a platinum treatment. However, since data in clinical trials often differ from routine clinical practice due to unselected population and less strict monitoring, "real life" experiences are very helpful to verify the efficacy of a new therapy. METHODS: This was a spontaneous, observational, retrospective study involving 43 patients with metastatic TCCU treated with vinflunine at our cancer center, data about demographics, disease characteristics, and previous treatments were collected and outcome and toxicities of vinflunine were analyzed. RESULTS: 41 of 43 patients were eligible for RR analysis, the Overall RR was 12%, the Disease Control Rate was 29%; when including only patients treated in II line the DCR rose to 33%; the median PFS and the median OS were 2.2 and 6.9 months, respectively. CONCLUSION: Our findings were consistent with the outcome data emerged in the phase III randomized trial and in the other observational studies conducted all around Europe in the last 2-3 years. This experience supports the use of vinflunine in patients with advanced TTCU as effective and manageable antineoplastic drug. PMID- 27199754 TI - Rifampin Regulation of Drug Transporters Gene Expression and the Association of MicroRNAs in Human Hepatocytes. AB - Membrane drug transporters contribute to the disposition of many drugs. In human liver, drug transport is controlled by two main superfamilies of transporters, the solute carrier transporters (SLC) and the ATP Binding Cassette transporters (ABC). Altered expression of these transporters due to drug-drug interactions can contribute to differences in drug exposure and possibly effect. In this study, we determined the effect of rifampin on gene expression of hundreds of membrane transporters along with all clinically relevant drug transporters. METHODS: In this study, primary human hepatocytes (n = 7 donors) were cultured and treated for 24 h with rifampin and vehicle control. RNA was isolated from the hepatocytes, mRNA expression was measured by RNA-seq, and miRNA expression was analyzed by Taqman OpenArray. The effect of rifampin on the expression of selected transporters was also tested in kidney cell lines. The impact of rifampin on the expression of 410 transporter genes from 19 different transporter gene families was compared with vehicle control. RESULTS: Expression patterns of 12 clinically relevant drug transporter genes were changed by rifampin (FDR < 0.05). For example, the expressions of ABCC2, ABCB1, and ABCC3 were increased 1.9 , 1.7-, and 1.2-fold, respectively. The effects of rifampin on four uptake drug transporters (SLCO1B3, SLC47A1, SLC29A1, SLC22A9) were negatively correlated with the rifampin effects on specific microRNA expression (SLCO1B3/miR-92a, SLC47A1/miR-95, SLC29A1/miR-30d#, and SLC22A9/miR-20; r < -0.79; p < 0.05). Seven hepatic drug transporter genes (SLC22A1, SLC22A5, SLC15A1, SLC29A1, SLCO4C1, ABCC2, and ABCC4), whose expression was altered by rifampin in hepatocytes, were also present in a renal proximal tubular cell line, but in renal cells rifampin did not alter their gene expression. PXR expression was very low in the kidney cells; this may explain why rifampin induces gene expression in a tissue-specific manner. CONCLUSION: Rifampin alters the expression of many of the clinically relevant hepatic drug transporters, which may provide a rational basis for understanding rifampin-induced drug-drug interactions reported in vivo. The relevance of its effect on many other transporters remains to be studied. PMID- 27199755 TI - The Role of Butylidenephthalide in Targeting the Microenvironment Which Contributes to Liver Fibrosis Amelioration. AB - The treatment of liver fibrosis has clinical limitations because of its multiple etiologies, such as epithelial-mesenchymal transition (EMT) promotion, cell regeneration and remodeling dysfunction, inflammatory cell activation, and scar tissue deposition. These factors might be considered as a new target for the fibrotic microenvironment, leading to increased fibrogenesis and liver fibrosis. Here, we investigate a small molecule named butylidenephthalide (BP) and its multiple effects on liver fibrosis treatment. Thioacetamide was used in vivo to induce chronic liver fibrosis. BP was administered orally in rats for a period of 2 and 4 weeks, which resulted in a significantly reduced fibrosis score (p < 0.05) and (p < 0.001), respectively. The inflammatory reaction of macrophage infiltration were reduced in the administration of BP, which led to the decrease in the transaminase levels. Moreover, we also found liver functions recovering (due to the increased serum albumin and reduced prothrombin time) where liver cells regenerated, which can be seen in the increase of Ki-67 on Oval cell. In addition, the fibrotic scar was also reduced, along with the expression of matrix metalloprotease by hepatic stellate cell. Furthermore, regarding the mechanism/study of EMT reduced by BP, the knockdown of BMP-7, which could reduce alpha-SMA expression, was mediated by the regulation of TGF-beta, which implies its major role on EMT. Finally, in the in vivo study, BP treatment of liver fibrosis was reduced by Bmp7 knockdown in zebrafish, suggesting that BP leads to the reduction of liver fibrosis, which also depends on BMP-7 induction. These results suggest that BP had multiple targets for treating liver fibrosis in the following ways: reduction of EMT, decreasing inflammatory reaction, and liver cell proliferation. This multiple targets approach provided a new mechanism to treat liver injury and fibrosis. PMID- 27199756 TI - Phemindole, a Synthetic Di-indole Derivative Maneuvers the Store Operated Calcium Entry (SOCE) to Induce Potent Anti-Carcinogenic Activity in Human Triple Negative Breast Cancer Cells. AB - Triple-negative breast cancer (TNBC), is a specific subtype of epithelial breast tumors that are immuno-histochemically negative for the protein expression of the estrogen receptor (ER), the progesterone receptor (PR) and lack over expression/gene amplification of HER2. This subtype of breast cancers is highly metastatic, shows poor prognosis and hence represents an important clinical challenge to researchers worldwide. Thus alternative approaches of drug development for TNBC have gained utmost importance in the present times. Dietary indole and its derivatives have gained prominence as anti-cancer agents and new therapeutic approaches are being developed to target them against TNBC. But a major drawback with 3, 3'di Indolyl methane (DIM) is their poor bioavailability and high effective concentration against TNBC. However, the Aryl methyl ring substituted analogs of DIM display interesting anti-cancer activity in breast cancer cells. In the current study we report the synthesis of a novel synthetic aryl methyl ring substituted analog of DIM, named as Phemindole as an effective anti-tumor agent against TNBC cells. Furthermore, we enumerated that Phemindole caused reactive oxygen species mediated mitochondrial-dependent apoptosis in MDAMB-231 cells. Furthermore, Phemindole mediated Store Operated Calcium Entry (SOCE) retardation favored inactivation of STIM1 and henceforth activated ER stress to induce apoptosis in TNBC cells. Simultaneously, Phemindole was also found to restrict the in vitro cell migration through its anti mitotic property and pFAK regulation. Studies extended to ex ovo and in vivo mice models further validated the efficacy of Phemindole. Thus our results cumulatively propose Phemindole as a new chemotherapeutic regime which might be effective to target the deadly aspects of the TNBC. PMID- 27199757 TI - Systemic Dosing of Thymosin Beta 4 before and after Ischemia Does Not Attenuate Global Myocardial Ischemia-Reperfusion Injury in Pigs. AB - The use of cardiopulmonary bypass (CPB) and aortic cross-clamping causes myocardial ischemia-reperfusion injury (I-RI) and can lead to reduced postoperative cardiac function. We investigated whether this injury could be attenuated by thymosin beta 4 (TB4), a peptide which has showed cardioprotective effects. Pigs received either TB4 or vehicle and underwent CPB and aortic cross clamping for 60 min with cold intermittent blood-cardioplegia and were then followed for 30 h. Myocardial function and blood flow was studied by cardiac magnetic resonance and PET imaging. Tissue and plasma samples were analyzed to determine the amount of cardiomyocyte necrosis and apoptosis as well as pharmacokinetics of the peptide. In vitro studies were performed to assess its influence on blood coagulation and vasomotor tone. Serum levels of the peptide were increased after administration compared to control samples. TB4 did not decrease the amount of cell death. Cardiac function and global myocardial blood flow was similar between the study groups. At high doses a vasoconstrictor effect on mesentery arteries and a vasodilator effect on coronary arteries was observed and blood clot firmness was reduced when tested in the presence of an antiplatelet agent. Despite promising results in previous trials the cardioprotective effect of TB4 was not demonstrated in this model for global myocardial I-RI. PMID- 27199758 TI - Serial Measurements of Splanchnic Vein Diameters in Rats Using High-Frequency Ultrasound. AB - The purpose of this study was to investigate serial ultrasound imaging in rats as a fully non-invasive method to (1) quantify the diameters of splanchnic veins in real time as an indirect surrogate for the capacitance function of those veins, and (2) assess the effects of drugs on venous dimensions. A 21 MHz probe was used on anesthetized male Sprague-Dawley rats to collect images containing the portal vein (PV), superior mesenteric vein (SMV), abdominal inferior vena cava (IVC), and splenic vein (SpV; used as a landmark in timed studies) and the abdominal aorta (AA). Stable landmarks were established that allowed reproducible quantification of cross-sectional diameters within an animal. The average diameters of vessels measured every 5 min over 45 min remained within 0.75 +/- 0.15% (PV), 0.2 +/- 0.09% (SMV), 0.5 +/- 0.12% (IVC), and 0.38 +/- 0.06% (AA) of baseline (PV: 2.0 +/- 0.12 mm; SMV: 1.7 +/- 0.04 mm; IVC: 3.2 +/- 0.1 mm; AA: 2.3 +/- 0.14 mm). The maximal effects of the vasodilator sodium nitroprusside (SNP; 2 mg/kg, i.v. bolus) on venous diameters were determined 5 min post SNP bolus; the diameters of all noted veins were significantly increased by SNP, while mean arterial pressure (MAP) decreased 29 +/- 4 mmHg. By contrast, administration of the venoconstrictor sarafotoxin (S6c; 5 ng/kg, i.v. bolus) significantly decreased PV and SpV, but not IVC, SMV, or AA, diameters 5 min post S6c bolus; MAP increased by 6 +/- 2 mmHg. In order to determine if resting splanchnic vein diameters were stable over much longer periods of time, vessel diameters were measured every 2 weeks for 8 weeks. Measurements were found to be highly reproducible within animals over this time period. Finally, to evaluate the utility of vein imaging in a chronic condition, images were acquired from 4-week deoxycorticosterone acetate salt (DOCA-salt) hypertensive and normotensive (SHAM) control rats. All vessel diameters increased from baseline while MAP increased (67 +/- 4 mmHg) in DOCA-salt rats compared to SHAM at 4 weeks after pellet implantation. Vessel diameters remained unchanged in SHAM animals. Together, these results support serial ultrasound imaging as a non-invasive, reliable technique able to measure acute and chronic changes in the diameter of splanchnic veins in intact rats. PMID- 27199759 TI - Forced Degradation Studies of Ivabradine and In Silico Toxicology Predictions for Its New Designated Impurities. AB - All activities should aim to eliminate genotoxic impurities and/or protect the API against degradation. There is a necessity to monitor impurities from all classification groups, hence ivabradine forced degradation studies were performed. Ivabradine was proved to be quite durable active substance, but still new and with insufficient stability data. Increased temperature, acid, base, oxidation reagents and light were found to cause its degradation. Degradation products were determined with the usage of HPLC equipped with Q-TOF-MS detector. Calculations of pharmacological and toxicological properties were performed for six identified degradation products. Target prediction algorithm was applied on the basis of Hyperpolarization-activated cyclic nucleotide-gated cation channels, as well as more general parameters like logP and aqueous solubility. Ames test and five cytochromes activities were calculated for toxicity assessment for selected degradation products. Pharmacological activity of photodegradation product (UV4), which is known as active metabolite, was qualified and identified. Two other degradation compounds (Ox1 and N1), which were formed during degradation process, were found to be pharmacologically active. PMID- 27199761 TI - A Challenge for a Male Noctuid Moth? Discerning the Female Sex Pheromone against the Background of Plant Volatiles. AB - Finding a partner is an essential task for members of all species. Like many insects, females of the noctuid moth Heliothis virescens release chemical cues consisting of a species-specific pheromone blend to attract conspecific males. While tracking these blends, male moths are also continuously confronted with a wide range of other odor molecules, many of which are plant volatiles. Therefore, we analyzed how background plant odors influence the degree of male moth attraction to pheromones. In order to mimic a natural situation, we tracked pheromone-guided behavior when males were presented with the headspaces of each of two host plants in addition to the female pheromone blend. Since volatile emissions are also dependent on the physiological state of the plant, we compared pheromone attraction in the background of both damaged and intact plants. Surprisingly, our results show that a natural odor bouquet does not influence flight behavior at all, although previous studies had shown a suppressive effect at the sensory level. We also chose different concentrations of single plant emitted volatiles, which have previously been shown to be neurophysiologically relevant, and compared their influence on pheromone attraction. We observed that pheromone attraction in male moths was significantly impaired in a concentration dependent manner when single plant volatiles were added. Finally, we quantified the amounts of volatile emission in our experiments using gas chromatography. Notably, when the natural emissions of host plants were compared with those of the tested single plant compounds, we found that host plants do not release volatiles at concentrations that impact pheromone-guided flight behavior of the moth. Hence, our results lead to the conclusion that pheromone-plant interactions in Heliothis virescens might be an effect of stimulation with supra-natural plant odor concentrations, whereas under more natural conditions the olfactory system of the male moth appears to be well adapted to follow the female pheromone plume without interference from plant-emitted odors. PMID- 27199762 TI - Acute Endurance Exercise Induces Nuclear p53 Abundance in Human Skeletal Muscle. AB - PURPOSE: The tumor suppressor protein p53 may have regulatory roles in exercise response-adaptation processes such as mitochondrial biogenesis and autophagy, although its cellular location largely governs its biological role. We investigated the subcellular localization of p53 and selected signaling targets in human skeletal muscle following a single bout of endurance exercise. METHODS: Sixteen, untrained individuals were pair-matched for aerobic capacity (VO2peak) and allocated to either an exercise (EX, n = 8) or control (CON, n = 8) group. After a resting muscle biopsy, EX performed 60 min continuous cycling at ~70% of VO2peak during which time CON subjects rested. A further biopsy was obtained from both groups 3 h post-exercise (EX) or 4 h after the first biopsy (CON). RESULTS: Nuclear p53 increased after 3 h recovery with EX only (~48%, p < 0.05) but was unchanged in the mitochondrial or cytoplasmic fractions in either group. Autophagy protein 5 (Atg-5) decreased in the mitochondrial protein fraction 3 h post-EX (~69%, P < 0.05) but remained unchanged in CON. There was an increase in cytoplasmic levels of the mitophagy marker PINK1 following 3 h of rest in CON only (~23%, P < 0.05). There were no changes in mitochondrial, nuclear, or cytoplasmic levels of PGC-1alpha post-exercise in either group. CONCLUSIONS: The selective increase in nuclear p53 abundance following endurance exercise suggests a potential pro-autophagy response to remove damaged proteins and organelles prior to initiating mitochondrial biogenesis and remodeling responses in untrained individuals. PMID- 27199764 TI - Greater Strength Gains after Training with Accentuated Eccentric than Traditional Isoinertial Loads in Already Strength-Trained Men. AB - As training experience increases it becomes more challenging to induce further neuromuscular adaptation. Consequently, strength trainers seek alternative training methods in order to further increase strength and muscle mass. One method is to utilize accentuated eccentric loading, which applies a greater external load during the eccentric phase of the lift as compared to the concentric phase. Based upon this practice, the purpose of this study was to determine the effects of 10 weeks of accentuated eccentric loading vs. traditional isoinertial resistance training in strength-trained men. Young (22 +/ 3 years, 177 +/- 6 cm, 76 +/- 10 kg, n = 28) strength-trained men (2.6 +/- 2.2 years experience) were allocated to concentric-eccentric resistance training in the form of accentuated eccentric load (eccentric load = concentric load + 40%) or traditional resistance training, while the control group continued their normal unsupervised training program. Both intervention groups performed three sets of 6-RM (session 1) and three sets of 10-RM (session 2) bilateral leg press and unilateral knee extension exercises per week. Maximum force production was measured by unilateral isometric (110 degrees knee angle) and isokinetic (concentric and eccentric 30 degrees .s(-1)) knee extension tests, and work capacity was measured by a knee extension repetition-to-failure test. Muscle mass was assessed using panoramic ultrasonography and dual-energy x-ray absorptiometry. Surface electromyogram amplitude normalized to maximum M-wave and the twitch interpolation technique were used to examine maximal muscle activation. After training, maximum isometric torque increased significantly more in the accentuated eccentric load group than control (18 +/- 10 vs. 1 +/- 5%, p < 0.01), which was accompanied by an increase in voluntary activation (3.5 +/- 5%, p < 0.05). Isokinetic eccentric torque increased significantly after accentuated eccentric load training only (10 +/- 9%, p < 0.05), whereas concentric torque increased equally in both the accentuated eccentric load (10 +/- 9%, p < 0.01) and traditional (9 +/- 6%, p < 0.01) resistance training groups; however, the increase in the accentuated eccentric load group was significantly greater (p < 0.05) than control (1 +/- 7%). Knee extension repetition-to-failure improved in the accentuated eccentric load group only (28%, p < 0.05). Similar increases in muscle mass occurred in both intervention groups. In summary, accentuated eccentric load training led to greater increases in maximum force production, work capacity and muscle activation, but not muscle hypertrophy, in strength trained individuals. PMID- 27199763 TI - Transient Hepatic Overexpression of Insulin-Like Growth Factor 2 Induces Free Cholesterol and Lipid Droplet Formation. AB - Although insulin-like growth factor 2 (IGF2) has been reported to be overexpressed in steatosis and steatohepatitis, a causal role of IGF2 in steatosis development remains elusive. Aim of our study was to decipher the role of IGF2 in steatosis development. Hydrodynamic gene delivery of an Igf2 plasmid used for transient Igf2 overexpression employing codon-optimized plasmid DNA resulted in a strong induction of hepatic Igf2 expression. The exogenously delivered Igf2 had no influence on endogenous Igf2 expression. The downstream kinase AKT was activated in Igf2 animals. Decreased ALT levels mirrored the cytoprotective effect of IGF2. Serum cholesterol was increased and sulfo-phospho vanillin colorimetric assay confirmed lipid accumulation in Igf2-livers while no signs of inflammation were observed. Interestingly, hepatic cholesterol and phospholipids, determined by thin layer chromatography, and free cholesterol by filipin staining, were specifically increased. Lipid droplet (LD) size was not changed, but their number was significantly elevated. Furthermore, free cholesterol, which can be stored in LDs and has been reported to be critical for steatosis progression, was elevated in Igf2 overexpressing mice. Accordingly, Hmgcr/HmgCoAR was upregulated. To have a closer look at de novo lipid synthesis we investigated expression of the lipogenic transcription factor SREBF1 and its target genes. SREBF1 was induced and also SREBF1 target genes were slightly upregulated. Interestingly, the expression of Cpt1a, which is responsible for mitochondrial fatty acid oxidation, was induced. Hepatic IGF2 expression induces a fatty liver, characterized by increased cholesterol and phospholipids leading to accumulation of LDs. We therefore suggest a causal role for IGF2 in hepatic lipid accumulation. PMID- 27199765 TI - Status of and Future Research on Thermosensory Processing. AB - Thermosensation is critically important for survival of all animals. In the cockroach Periplaneta americana, thermoreceptor neurons on antennae and thermosensory interneurons in the antennal lobe have been characterized electrophysiologically, and recent studies using advanced transgenic technologies in the fruit fly Drosophila melanogaster have added much to the knowledge of these neurons, enabling us to discuss common principles of thermosensory processing systems in insects. Cockroaches and many other insects possess only one type of thermoreceptor neurons on antennae that are excited by cooling and inhibited by warming. In contrast, the antennae of fruit flies and other dipterans possess oppositely responding warm and cold receptor neurons. Despite differences in their thermoreceptive equipment, central processing of temperature information is much the same in flies and cockroaches. Axons of thermoreceptor neurons project to the margin of the antennal lobe and form glomeruli, from which cold, warm and cold-warm projection neurons originate, the last neurons being excited by both cooling and warming. Axons of antennal lobe thermosensory projection neurons of the antennal lobe terminate in three distinct areas of the protocerebrum, the mushroom body, lateral horn and posterior lateral protocerebrum, the last area also receiving termination of hygrosensory projection neurons. Such multiple thermosensory pathways may serve to control multiple forms of thermosensory behavior. Electrophysiological studies on cockroaches and transgenic approaches in flies are encouraged to complement each other for further elucidating general principles of thermosensory processing in the insect brain. PMID- 27199766 TI - Association with Amino Acids Does Not Enhance Efficacy of Polymerized Liposomes As a System for Lung Gene Delivery. AB - Development of improved drug and gene delivery systems directly into the lungs is highly desirable given the important burden of respiratory diseases. We aimed to evaluate the safety and efficacy of liposomes composed of photopolymerized lipids [1,2-bis-(tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine] associated with amino acids as vectors for gene delivery into the lungs of healthy animals. Lipopolymer vesicles, in particular, are more stable than other types of liposomes. In this study, lipopolymers were associated with l-arginine, l tryptophan, or l-cysteine. We hypothesized that the addition of these amino acids would enhance the efficacy of gene delivery to the lungs by the lipopolymers. l Arginine showed the highest association efficiency due to its positive charge and better surface interactions. None of the formulations caused inflammation or altered lung mechanics, suggesting that these lipopolymers can be safely administered as aerosols. All formulations were able to induce eGFP mRNA expression in lung tissue, but the addition of amino acids reduced delivery efficacy when compared with the simple lipopolymer particle. These results indicate that this system could be further explored for gene or drug delivery targeting lung diseases. PMID- 27199760 TI - Calcium-Sensing Receptors of Human Neural Cells Play Crucial Roles in Alzheimer's Disease. AB - In aged subjects, late-onset Alzheimer's disease (LOAD) starts in the lateral entorhinal allocortex where a failure of clearance mechanisms triggers an accumulation of neurotoxic amyloid-beta42 oligomers (Abeta42-os). In neurons and astrocytes, Abeta42-os enhance the transcription of Abeta precursor protein (APP) and beta-secretase/BACE1 genes. Thus, by acting together with gamma-secretase, the surpluses of APP and BACE1 amplify the endogenous production of Abeta42-os which pile up, damage mitochondria, and are oversecreted. At the plasmalemma, exogenous Abeta42-os bind neurons' and astrocytes' calcium-sensing receptors (CaSRs) activating a set of intracellular signaling pathways which upkeep Abeta42 os intracellular accumulation and oversecretion by hindering Abeta42-os proteolysis. In addition, Abeta42-os accumulating in the extracellular milieu spread and reach mounting numbers of adjacent and remoter teams of neurons and astrocytes which in turn are recruited, again via Abeta42-os*CaSR-governed mechanisms, to produce and release additional Abeta42-os amounts. This relentless self-sustaining mechanism drives AD progression toward upper cortical areas. Later on accumulating Abeta42-os elicit the advent of hyperphosphorylated (p)-Tau oligomers which acting together with Abeta42-os and other glial neurotoxins cooperatively destroy wider and wider cognition-related cortical areas. In parallel, Abeta42-os*CaSR signals also elicit an excess production and secretion of nitric oxide and vascular endothelial growth factor-A from astrocytes, of Abeta42-os and myelin basic protein from oligodendrocytes, and of proinflammatory cytokines, nitric oxide and (likely) Abeta42-os from microglia. Activated astrocytes and microglia survive the toxic onslaught, whereas neurons and oligodendrocytes increasingly die. However, we have shown that highly selective allosteric CaSR antagonists (calcilytics), like NPS 2143 and NPS 89626, efficiently suppress all the neurotoxic effects Abeta42-os*CaSR signaling drives in cultured cortical untransformed human neurons and astrocytes. In fact, calcilytics increase Abeta42 proteolysis and discontinue the oversecretion of Abeta42-os, nitric oxide, and vascular endothelial growth factor-A from both astrocytes and neurons. Seemingly, calcilytics would also benefit the other types of glial cells and cerebrovascular cells otherwise damaged by the effects of Abeta42-os*CaSR signaling. Thus, given at amnestic minor cognitive impairment (aMCI) or initial symptomatic stages, calcilytics could prevent or terminate the propagation of LOAD neuropathology and preserve human neurons' viability and hence patients' cognitive abilities. PMID- 27199768 TI - Toxic Effects of Zinc Chloride on the Bone Development in Danio rerio (Hamilton, 1822). AB - The increase of heavy metals in the environment involves a high exposure of aquatic organisms to these pollutants. The present study is planned to investigate the effects of zinc chloride (ZnCl2) on the bone embryonic development of Danio rerio and confirm the use of zebrafish as a model organism to study the teratogenic potential of this pollutant. Zebrafish embryos were exposed to different ZnCl2 concentrations and analyzed by ICP-MS. The skeletal anomalies were evaluated to confocal microscope after staining with calcein solution and RhodZin(TM)-3,AM. The data show a delay in hatching compared with the controls, malformations in the process of calcification and significant defects in growth. In conclusion, the current work demonstrates for the first time the Zn toxic effects on calcification process and confirm zebrafish (Danio rerio) as suitable alternative vertebrate model to study the causes and the mechanisms of the skeletal malformations. PMID- 27199767 TI - Sex Steroids Modulate Uterine-Placental Vasculature: Implications for Obstetrics and Neonatal Outcomes. AB - Adequate blood supply to the uterine-placental region is crucial to ensure the transport of oxygen and nutrients to the growing fetus. Multiple factors intervene to achieve appropriate uterine blood flow and the structuring of the placental vasculature during the early stages of pregnancy. Among these factors, oxygen concentrations, growth factors, cytokines, and steroid hormones are the most important. Sex steroids are present in extremely high concentrations in the maternal circulation and are important paracrine and autocrine regulators of a wide range of maternal and placental functions. In this regard, progesterone and estrogens act as modulators of uterine vessels and decrease the resistance of the spiral uterine arteries. On the other hand, androgens have the opposite effect, increasing the vascular resistance of the uterus. Moreover, progesterone and estrogens modulate the synthesis and release of angiogenic factors by placental cells, which regulates trophoblastic invasion and uterine artery remodeling. In this scenario, it is not surprising that women with pregnancy-related pathologies, such as early miscarriages, preterm delivery, preeclampsia, and fetal growth restriction, exhibit altered sex steroid concentrations. PMID- 27199769 TI - Heritability of ECG Biomarkers in the Netherlands Twin Registry Measured from Holter ECGs. AB - INTRODUCTION: The resting ECG is the most commonly used tool to assess cardiac electrophysiology. Previous studies have estimated heritability of ECG parameters based on these snapshots of the cardiac electrical activity. In this study we set out to determine whether analysis of heart rate specific data from Holter ECGs allows more complete assessment of the heritability of ECG parameters. METHODS AND RESULTS: Holter ECGs were recorded from 221 twin pairs and analyzed using a multi-parameter beat binning approach. Heart rate dependent estimates of heritability for QRS duration, QT interval, Tpeak-Tend and Theight were calculated using structural equation modeling. QRS duration is largely determined by environmental factors whereas repolarization is primarily genetically determined. Heritability estimates of both QT interval and Theight were significantly higher when measured from Holter compared to resting ECGs and the heritability estimate of each was heart rate dependent. Analysis of the genetic contribution to correlation between repolarization parameters demonstrated that covariance of individual ECG parameters at different heart rates overlap but at each specific heart rate there was relatively little overlap in the genetic determinants of the different repolarization parameters. CONCLUSIONS: Here we present the first study of heritability of repolarization parameters measured from Holter ECGs. Our data demonstrate that higher heritability can be estimated from the Holter than the resting ECG and reveals rate dependence in the genetic environmental determinants of the ECG that has not previously been tractable. Future applications include deeper dissection of the ECG of participants with inherited cardiac electrical disease. PMID- 27199770 TI - Effects of Age, Exercise Duration, and Test Conditions on Heart Rate Variability in Young Endurance Horses. AB - Although cardiac recovery is an important criterion for ranking horses in endurance competitions, heart rate variability (HRV) has hardly ever been studied in the context of this equestrian discipline. In the present study, we sought to determine whether HRV is affected by parameters such as age, exercise duration and test site. Accordingly, HRV might be used to select endurance horses with the fastest cardiac recovery. The main objective of the present study was to determine the effects of age, exercise duration, and test site on HRV variables at rest and during exercise and recovery in young Arabian endurance horses. Over a 3-year period, 77 young Arabian horses aged 4-6 years performed one or more exercise tests (consisting of a warm-up, cantering at 22 km.h(-1)and a final 500 m gallop at full speed) at four different sites. Beat-to-beat RR intervals were continuously recorded and then analyzed (using a time-frequency approach) to determine the instantaneous HRV components before, during and after the test. At rest, the root-mean-square of successive differences in RR intervals (RMSSD) was higher in the 4-year-olds (54.4 +/- 14.5 ms) than in the 5-or 6-year-olds (44.9 +/- 15.5 and 49.1 +/- 11.7 ms, respectively). During the first 15 min of exercise (period T), the heart rate (HR) and RMSSD decreased with age. In 6-year-olds, RMSSD decreased as the exercise duration increased (T: 3.0 +/- 1.4 vs. 2T: 3.6 +/ 2.2 vs. 3T: 2.8 +/- 1.0). During recovery, RMSSD was negatively correlated with the cardiac recovery time (CRT) and the recovery heart rate (RHR; R = -0.56 and 0.53, respectively; p < 0.05). At rest and during exercise and recovery, RMSSD and several HRV variables differed significantly as a function of the test conditions. HRV in endurance horses appears to be strongly influenced by age and environmental factors (such as ambient temperature, ambient humidity, and track quality). Nevertheless, RMSSD can be used to select endurance horses with the fastest cardiac recovery. PMID- 27199773 TI - Young, Healthy Subjects Can Reduce the Activity of Calf Muscles When Provided with EMG Biofeedback in Upright Stance. AB - Recent evidence suggests the minimization of muscular effort rather than of the size of bodily sway may be the primary, nervous system goal when regulating the human, standing posture. Different programs have been proposed for balance training; none however has been focused on the activation of postural muscles during standing. In this study we investigated the possibility of minimizing the activation of the calf muscles during standing through biofeedback. By providing subjects with an audio signal that varied in amplitude and frequency with the amplitude of surface electromyograms (EMG) recorded from different regions of the gastrocnemius and soleus muscles, we expected them to be able to minimize the level of muscle activation during standing without increasing the excursion of the center of pressure (CoP). CoP data and surface EMG from gastrocnemii, soleus and tibialis anterior muscles were obtained from 10 healthy participants while standing at ease and while standing with EMG biofeedback. Four sensitivities were used to test subjects' responsiveness to the EMG biofeedback. Compared with standing at ease, the two most sensitive feedback conditions induced a decrease in plantar flexor activity (~15%; P < 0.05) and an increase in tibialis anterior EMG (~10%; P < 0.05). Furthermore, CoP mean position significantly shifted backward (~30 mm). In contrast, the use of less sensitive EMG biofeedback resulted in a significant decrease in EMG activity of ankle plantar flexors with a marginal increase in TA activity compared with standing at ease. These changes were not accompanied by greater CoP displacements or significant changes in mean CoP position. Key results revealed subjects were able to keep standing stability while reducing the activity of gastrocnemius and soleus without loading their tibialis anterior muscle when standing with EMG biofeedback. These results may therefore posit the basis for the development of training protocols aimed at assisting subjects in more efficiently controlling leg muscle activity during standing. PMID- 27199774 TI - Thinking and Action: A Cognitive Perspective on Self-Regulation during Endurance Performance. AB - Self-regulation reflects an individual's efforts to bring behavior and thinking into line with often consciously desired goals. During endurance activity, self regulation requires an athlete to balance their speed or power output appropriately to achieve an optimal level of performance. Considering that both behavior and thinking are core elements of self-regulation, this article provides a cognitive perspective on the processes required for effective pace-regulation during endurance performance. We also integrate this viewpoint with physiological and performance outcomes during activity. As such, evidence is presented to suggest that what an athlete thinks about has an important influence on effort perceptions, physiological outcomes, and, consequently, endurance performance. This article also provides an account of how an athlete might control their cognition and focus attention during an endurance event. We propose that effective cognitive control during performance requires both proactive, goal driven processes and reactive, stimulus-driven processes. In addition, the role of metacognition-or thinking about thinking-in pace-regulation will also be considered. Metacognition is an essential component of self-regulation and its primary functions are to monitor and control the thoughts and actions required for task completion. To illustrate these processes in action, a metacognitive framework of attentional focus and cognitive control is applied to an endurance performance setting: specifically, Bradley Wiggins' successful 2015 Hour record attempt in cycling. Finally, future perspectives will consider the potentially deleterious effects of the sustained cognitive effort required during prolonged and strenuous endurance tasks. PMID- 27199771 TI - Emerging Roles of Hydrogen Sulfide in Inflammatory and Neoplastic Colonic Diseases. AB - Hydrogen sulfide (H2S) is a toxic gas that has been recognized as an important mediator of many physiological processes, such as neurodegeneration, regulation of inflammation, blood pressure, and metabolism. In the human colon, H2S is produced by both endogenous enzymes and sulfate-reducing bacteria (SRB). H2S is involved in the physiological and pathophysiological conditions of the colon, such as inflammatory bowel disease (IBD) and colorectal cancer (CRC), which makes the pharmacological modulation of H2S production and metabolism a potential chemical target for the treatment of colonic diseases. However, the exact mechanisms and pathways by which H2S-mediates normal physiological function and disease in the colon are not fully understood. Besides, the production and release of H2S are modulated by both endogenous and exogenous factors. This review will discuss the production and storage of H2S, its biological roles and the emerging importance in physiology and pathology of IBD and CRC. PMID- 27199772 TI - The Physiology of Bone Pain. How Much Do We Really Know? AB - Pain is associated with most bony pathologies. Clinical and experimental observations suggest that bone pain can be derived from noxious stimulation of the periosteum or bone marrow. Sensory neurons are known to innervate the periosteum and marrow cavity, and most of these have a morphology and molecular phenotype consistent with a role in nociception. However, little is known about the physiology of these neurons, and therefore information about mechanisms that generate and maintain bone pain is lacking. The periosteum has received greater attention relative to the bone marrow, reflecting the easier access of the periosteum for experimental assessment. With the electrophysiological preparations used, investigators have been able to record from single periosteal units in isolation, and there is a lot of information available about how they respond to different stimuli, including those that are noxious. In contrast, preparations used to study sensory neurons that innervate the bone marrow have been limited to recording multi-unit activity in whole nerves, and whilst they clearly report responses to noxious stimulation, it is not possible to define responses for single sensory neurons that innervate the bone marrow. There is only limited evidence that peripheral sensory neurons that innervate bone can be sensitized or that they can be activated by multiple stimulus types, and at present this only exists in part for periosteal units. In the central nervous system, it is clear that spinal dorsal horn neurons can be activated by noxious stimuli applied to bone. Some can be sensitized under pathological conditions and may contribute in part to secondary or referred pain associated with bony pathology. Activity related to stimulation of sensory nerves that innervate bone has also been reported in neurons of the spinoparabrachial pathway and the somatosensory cortices, both known for roles in coding information about pain. Whilst these provide some clues as to the way information about bone pain is centrally coded, they need to be expanded to further our understanding of other central territories involved. There is a lot more to learn about the physiology of peripheral sensory neurons that innervate bone and their central projections. PMID- 27199775 TI - Insights into the Pathology of the alpha2-Na(+)/K(+)-ATPase in Neurological Disorders; Lessons from Animal Models. AB - A functional Na(+)/K(+)-ATPase consists of a catalytic alpha subunit and a regulatory beta subunit. Four alpha isoforms of the Na(+)/K(+)-ATPase are found in mammals, each with a unique expression pattern and catalytic activity. The alpha2 isoform, encoded by the ATP1A2 gene, is primarily found in the central nervous system (CNS) and in heart-, skeletal- and smooth muscle tissues. In the CNS, the alpha2 isoform is mainly expressed in glial cells. In particular, the alpha2 isoform is found in astrocytes, important for astrocytic K(+) clearance and, consequently, the indirect uptake of neurotransmitters. Both processes are essential for proper brain activity, and autosomal dominantly mutations in the ATP1A2 gene cause the neurological disorder Familial hemiplegic migraine type 2 (FHM2). FHM2 is a severe subtype of migraine with aura including temporary numbness or weakness, and affecting only one side of the body. FHM2 patients often suffer from neurological comorbidities such as seizures, sensory disturbances, cognitive impairment, and psychiatric manifestations. The functional consequences of FHM2 disease mutations leads to a partial or complete loss of function of pump activity; however, a clear phenotype-genotype correlation has yet to be elucidated. Gene-modified mouse models targeting the Atp1a2 gene have proved instrumental in the understanding of the pathology of FHM2. Several Atp1a2 knockout (KO) mice targeting different exons have been reported. Homozygous Atp1a2 KO mice die shortly after birth due to respiratory malfunction resulting from abnormal Cl(-) homeostasis in brainstem neurons. Heterozygous KO mice are viable, but display altered behavior and neurological deficits such as altered spatial learning, decreased motor activity and enhanced fear/anxiety compared to wild type mice. FHM2 knock-in (KI) mouse models carrying the human in vivo disease mutations W887R and G301R have also been reported. Both models display altered cortical spreading depression (CSD) and point to deficits in the glutamatergic system as the main underlying mechanism of FHM2. PMID- 27199776 TI - Improving Social Cognition in People with Schizophrenia with RC2S: Two Single Case Studies. AB - Difficulties in social interactions are a central characteristic of people with schizophrenia, and can be partly explained by impairments of social cognitive processes. New strategies of cognitive remediation have been recently developed to target these deficits. The RC2S therapy is an individualized and partly computerized program through which patients practice social interactions and develop social cognitive abilities with simulation techniques in a realistic environment. Here, we present the results of two case-studies involving two patients with schizophrenia presenting with specific profiles of impaired social cognition. Each patient completed three baseline sessions, 14 treatment sessions, and 3 follow-up sessions at the end of the therapy - and for 1 patient, another 3 sessions 9 months later. We used a multiple baseline design to assess specific components of social cognition according to the patients' profiles. Functioning and symptomatology were also assessed at the end of the treatment and 6 months later. Results highlight significant improvements in the targeted social cognitive processes and positive changes in functioning in the long term. The RC2S program seems, thus, to be a new useful program for social cognitive remediation in schizophrenia. PMID- 27199777 TI - GOLIAH: A Gaming Platform for Home-Based Intervention in Autism - Principles and Design. AB - Children with Autism need intensive intervention and this is challenging in terms of manpower, costs, and time. Advances in Information Communication Technology and computer gaming may help in this respect by creating a nomadically deployable closed-loop intervention system involving the child and active participation of parents and therapists. An automated serious gaming platform enabling intensive intervention in nomadic settings has been developed by mapping two pivotal skills in autism spectrum disorder: Imitation and Joint Attention (JA). Eleven games - seven Imitations and four JA - were derived from the Early Start Denver Model. The games involved application of visual and audio stimuli with multiple difficulty levels and a wide variety of tasks and actions pertaining to the Imitation and JA. The platform runs on mobile devices and allows the therapist to (1) characterize the child's initial difficulties/strengths, ensuring tailored and adapted intervention by choosing appropriate games and (2) investigate and track the temporal evolution of the child's progress through a set of automatically extracted quantitative performance metrics. The platform allows the therapist to change the game or its difficulty levels during the intervention depending on the child's progress. Performance of the platform was assessed in a 3-month open trial with 10 children with autism (Trial ID: NCT02560415, Clinicaltrials.gov). The children and the parents participated in 80% of the sessions both at home (77.5%) and at the hospital (90%). All children went through all the games but, given the diversity of the games and the heterogeneity of children profiles and abilities, for a given game the number of sessions dedicated to the game varied and could be tailored through automatic scoring. Parents (N = 10) highlighted enhancement in the child's concentration, flexibility, and self-esteem in 78, 89, and 44% of the cases, respectively, and 56% observed an enhanced parents-child relationship. This pilot study shows the feasibility of using the developed gaming platform for home-based intensive intervention. However, the overall capability of the platform in delivering intervention needs to be assessed in a bigger open trial. PMID- 27199780 TI - Commentary: A Gene-Based Association Method for Mapping Traits Using Reference Transcriptome Data. PMID- 27199781 TI - Optical Topography in Psychiatry: A Chip Off the Old Block or a New Look Beyond the Mind-Brain Frontiers? PMID- 27199782 TI - The Synergistic Impact of Excessive Alcohol Drinking and Cigarette Smoking upon Prospective Memory. AB - The independent use of excessive amounts of alcohol or persistent cigarette smoking have been found to have a deleterious impact upon Prospective Memory (PM: remembering future intentions and activities), although to date, the effect of their concurrent use upon PM is yet to be explored. The present study investigated the impact of the concurrent use of drinking excessive amounts of alcohol and smoking cigarettes (a "Polydrug" group) in comparison to the combined effect of the single use of these substances upon PM. The study adopted a single factorial independent groups design. The Cambridge Prospective Memory Test (CAMPROMPT) is a test of both time-based and event-based PM and was used here to measure PM. The CAMPROMPT was administered to 125 adults; an excessive alcohol user group (n = 40), a group of smokers who drink very little alcohol (n = 20), a combined user group (the "Polydrug" group) who drink excessively and smoke cigarettes (n = 40) and a non-drinker/low alcohol consumption control group (n = 25). The main findings revealed that the Polydrug users recalled significantly fewer time-based PM tasks than both excessive alcohol users p < 0.001 and smokers p = 0.013. Polydrug users (mean = 11.47) also remembered significantly fewer event-based PM tasks than excessive alcohol users p < 0.001 and smokers p = 0.013. With regards to the main aim of the study, the polydrug users exhibited significantly greater impaired time-based PM than the combined effect of single excessive alcohol users and cigarette smokers p = 0.033. However, no difference was observed between polydrug users and the combined effect of single excessive alcohol users and cigarette smokers in event-based PM p = 0.757. These results provide evidence that concurrent (polydrug) use of these two substances has a synergistic effect in terms of deficits upon time-based PM. The observation that combined excessive drinking and cigarette smoking leads to a greater impairment in time-based PM may be of paramount importance, given the key role PM plays in everyday independent living. PMID- 27199783 TI - Promoting Health by Improving Subjective Sleep Quality? Reduction in Depressive Symptoms and Inflammation as Potential Mechanisms and Implications for Trauma Exposed Persons. PMID- 27199784 TI - Characteristics of Participants Enrolled in a Brief Motivational Enhancement for Smokers. AB - Daily smoking is associated with elevated blood pressure, carbon monoxide (CO) toxicity, and impaired pulmonary lung functioning. The benefits of successful smoking cessation are readily apparent, given the health improvements associated with cessation, as well as the reduction of secondhand smoke to which non-smoking coworkers and family members are exposed. Previous literature indicates that providing personalized information to smokers (versus general base rates) without engaging in confrontational pressure to quit smoking, leads to increased interest in quitting smoking and willingness to enter smoking cessation programs. The goal of this study was to examine the pretreatment characteristics of the smokers entering a brief motivational enhancement intervention based on personally tailored health feedback. Participants (N = 28) were 88.2% Caucasian and 59% males, and they were an average of 23 years of age. On average, they smoked 20.08 cigarettes per day for a mean of 6.6 years, a mean Fagerstrom Test for Nicotine Dependence score of 4.7, and obtained a mean breath CO reading of 19.1 ppm. Smoking-related adverse health outcomes were predictive of stages of change motivation to quit smoking. Implications for cessation programs are discussed. PMID- 27199785 TI - Cortico-Striato-Thalamo-Cortical Circuitry, Working Memory, and Obsessive Compulsive Disorder. PMID- 27199779 TI - Is there Progress? An Overview of Selecting Biomarker Candidates for Major Depressive Disorder. AB - Major depressive disorder (MDD) contributes to a significant worldwide disease burden, expected to be second only to heart disease by 2050. However, accurate diagnosis has been a historical weakness in clinical psychiatry. As a result, there is a demand for diagnostic modalities with greater objectivity that could improve on current psychiatric practice that relies mainly on self-reporting of symptoms and clinical interviews. Over the past two decades, literature on a growing number of putative biomarkers for MDD increasingly suggests that MDD patients have significantly different biological profiles compared to healthy controls. However, difficulty in elucidating their exact relationships within depression pathology renders individual markers inconsistent diagnostic tools. Consequently, further biomarker research could potentially improve our understanding of MDD pathophysiology as well as aid in interpreting response to treatment, narrow differential diagnoses, and help refine current MDD criteria. Representative of this, multiplex assays using multiple sources of biomarkers are reported to be more accurate options in comparison to individual markers that exhibit lower specificity and sensitivity, and are more prone to confounding factors. In the future, more sophisticated multiplex assays may hold promise for use in screening and diagnosing depression and determining clinical severity as an advance over relying solely on current subjective diagnostic criteria. A pervasive limitation in existing research is heterogeneity inherent in MDD studies, which impacts the validity of biomarker data. Additionally, small sample sizes of most studies limit statistical power. Yet, as the RDoC project evolves to decrease these limitations, and stronger studies with more generalizable data are developed, significant advances in the next decade are expected to yield important information in the development of MDD biomarkers for use in clinical settings. PMID- 27199778 TI - Acute Stress Decreases but Chronic Stress Increases Myocardial Sensitivity to Ischemic Injury in Rodents. AB - Cardiovascular disease (CVD) is the largest cause of mortality worldwide, and stress is a significant contributor to the development of CVD. The relationship between acute and chronic stress and CVD is well evidenced. Acute stress can lead to arrhythmias and ischemic injury. However, recent evidence in rodent models suggests that acute stress can decrease sensitivity to myocardial ischemia reperfusion injury (IRI). Conversely, chronic stress is arrhythmogenic and increases sensitivity to myocardial IRI. Few studies have examined the impact of validated animal models of stress-related psychological disorders on the ischemic heart. This review examines the work that has been completed using rat models to study the effects of stress on myocardial sensitivity to ischemic injury. Utilization of animal models of stress-related psychological disorders is critical in the prevention and treatment of cardiovascular disorders in patients experiencing stress-related psychiatric conditions. PMID- 27199786 TI - Early Memories of Individuals on the Autism Spectrum Assessed Using Online Self Reports. AB - "When I was one and a half years old, I was on a ferry lying on red seats" - while several autobiographical accounts by people with autism reveal vivid memories of early childhood, the vast amount of experimental investigations found deficits in personal autobiographic memory in autism. To assess this contradiction empirically, we implemented an online questionnaire on early childhood events to compare people on the autism spectrum (AS) and non-autistic people with respect to their earliest autobiographical episodic memories and the earliest semantic know event as told by another person. Results indicate that people on the AS do not differ from non-autistic people in the age of their earliest know events but remember events from an earlier age in childhood and with more sensory details, contradicting the assumption of an overall deficit in personal episodic memory in autism. Furthermore, our results emphasize the supporting influence of language for memory formation and give evidence for an important role of sensory features in memories of people on the AS. PMID- 27199788 TI - Action Identity in Style Simulation Systems: Do Players Consider Machine Generated Music As of Their Own Style? AB - The generation of musical material in a given style has been the subject of many studies with the increased sophistication of artificial intelligence models of musical style. In this paper we address a question of primary importance for artificial intelligence and music psychology: can such systems generate music that users indeed consider as corresponding to their own style? We address this question through an experiment involving both performance and recognition tasks with musically naive school-age children. We asked 56 children to perform a free form improvisation from which two kinds of music excerpt were created. One was a mere recording of original performances. The other was created by a software program designed to simulate the participants' style, based on their original performances. Two hours after the performance task, the children completed the recognition task in two conditions, one with the original excerpts and one with machine-generated music. Results indicate that the success rate is practically equivalent in two conditions: children tended to make correct attribution of the excerpts to themselves or to others, whether the music was human-produced or machine-generated (mean accuracy = 0.75 and = 0.71, respectively). We discuss this equivalence in accuracy for machine-generated and human produced music in the light of the literature on memory effects and action identity which addresses the recognition of one's own production. PMID- 27199787 TI - Overlapping Mechanisms of Stress-Induced Relapse to Opioid Use Disorder and Chronic Pain: Clinical Implications. AB - Over the past two decades, a steeply growing number of persons with chronic non cancer pain have been using opioid analgesics chronically to treat it, accompanied by a markedly increased prevalence of individuals with opioid-related misuse, opioid use disorders, emergency department visits, hospitalizations, admissions to drug treatment programs, and drug overdose deaths. This opioid misuse and overdose epidemic calls for well-designed randomized-controlled clinical trials into more skillful and appropriate pain management and for developing effective analgesics that have lower abuse liability and are protective against stress induced by chronic non-cancer pain. However, incomplete knowledge regarding effective approaches to treat various types of pain has been worsened by an under-appreciation of overlapping neurobiological mechanisms of stress, stress-induced relapse to opioid use, and chronic non-cancer pain in patients presenting for care for these conditions. This insufficient knowledge base has unfortunately encouraged common prescription of conveniently available opioid pain-relieving drugs with abuse liability, as opposed to treating underlying problems using team-based multidisciplinary, patient-centered, collaborative-care approaches for addressing pain and co-occurring stress and risk for opioid use disorder. This paper reviews recent neurobiological findings regarding overlapping mechanisms of stress-induced relapse to opioid misuse and chronic non-cancer pain, and then discusses these in the context of key outstanding evidence gaps and clinical-treatment research directions that may be pursued to fill these gaps. Such research directions, if conducted through well designed randomized-controlled trials, may substantively inform clinical practice in general medical settings on how to effectively care for patients presenting with pain-related distress and these common co-occurring conditions. PMID- 27199790 TI - Three Factors Are Critical in Order to Synthesize Intelligible Noise-Vocoded Japanese Speech. AB - Factor analysis (principal component analysis followed by varimax rotation) had shown that 3 common factors appear across 20 critical-band power fluctuations derived from spoken sentences of eight different languages [Ueda et al. (2010). Fechner Day 2010, Padua]. The present study investigated the contributions of such power-fluctuation factors to speech intelligibility. The method of factor analysis was modified to obtain factors suitable for resynthesizing speech sounds as 20-critical-band noise-vocoded speech. The resynthesized speech sounds were used for an intelligibility test. The modification of factor analysis ensured that the resynthesized speech sounds were not accompanied by a steady background noise caused by the data reduction procedure. Spoken sentences of British English, Japanese, and Mandarin Chinese were subjected to this modified analysis. Confirming the earlier analysis, indeed 3-4 factors were common to these languages. The number of power-fluctuation factors needed to make noise-vocoded speech intelligible was then examined. Critical-band power fluctuations of the Japanese spoken sentences were resynthesized from the obtained factors, resulting in noise-vocoded-speech stimuli, and the intelligibility of these speech stimuli was tested by 12 native Japanese speakers. Japanese mora (syllable-like phonological unit) identification performances were measured when the number of factors was 1-9. Statistically significant improvement in intelligibility was observed when the number of factors was increased stepwise up to 6. The 12 listeners identified 92.1% of the morae correctly on average in the 6-factor condition. The intelligibility improved sharply when the number of factors changed from 2 to 3. In this step, the cumulative contribution ratio of factors improved only by 10.6%, from 37.3 to 47.9%, but the average mora identification leaped from 6.9 to 69.2%. The results indicated that, if the number of factors is 3 or more, elementary linguistic information is preserved in such noise-vocoded speech. PMID- 27199789 TI - Mathematics Anxiety: What Have We Learned in 60 Years? AB - The construct of mathematics anxiety has been an important topic of study at least since the concept of "number anxiety" was introduced by Dreger and Aiken (1957), and has received increasing attention in recent years. This paper focuses on what research has revealed about mathematics anxiety in the last 60 years, and what still remains to be learned. We discuss what mathematics anxiety is; how distinct it is from other forms of anxiety; and how it relates to attitudes to mathematics. We discuss the relationships between mathematics anxiety and mathematics performance. We describe ways in which mathematics anxiety is measured, both by questionnaires, and by physiological measures. We discuss some possible factors in mathematics anxiety, including genetics, gender, age, and culture. Finally, we describe some research on treatment. We conclude with a brief discussion of what still needs to be learned. PMID- 27199791 TI - Neural Correlates of Sex/Gender Differences in Humor Processing for Different Joke Types. AB - Humor operates through a variety of techniques, which first generate surprise and then amusement and laughter once the unexpected incongruity is resolved. As different types of jokes use different techniques, the corresponding humor processes also differ. The present study builds on the framework of the 'tri component theory of humor,' which details the mechanisms involved in cognition (comprehension), affect (appreciation), and laughter (expression). This study seeks to identify differences among joke types and between sexes/genders in the neural mechanisms underlying humor processing. Three types of verbal jokes, bridging-inference jokes (BJs), exaggeration jokes (EJs), and ambiguity jokes (AJs), were used as stimuli. The findings revealed differences in brain activity for an interaction between sex/gender and joke type. For BJs, women displayed greater activation in the temporoparietal-mesocortical-motor network than men, demonstrating the importance of the temporoparietal junction (TPJ) presumably for 'theory of mind' processing, the orbitofrontal cortex for motivational functions and reward coding, and the supplementary motor area for laughter. Women also showed greater activation than men in the frontal-mesolimbic network associated with EJs, including the anterior (frontopolar) prefrontal cortex (aPFC, BA 10) for executive control processes, and the amygdala and midbrain for reward anticipation and salience processes. Conversely, AJs elicited greater activation in men than women in the frontal-paralimbic network, including the dorsal prefrontal cortex (dPFC) and parahippocampal gyrus. All joke types elicited greater activation in the aPFC of women than of men, whereas men showed greater activation than women in the dPFC. To confirm the findings related to sex/gender differences, random group analysis and within group variance analysis were also performed. These findings help further establish the mechanisms underlying the processing of different joke types for the sexes/genders and provide a neural foundation for a theory of sex/gender differences in humor. PMID- 27199793 TI - The Role of Inhibition in Age-related Off-Topic Verbosity: Not Access but Deletion and Restraint Functions. AB - The speech of older adults is commonly described as verbose and off-topic, which is thought to influence their social communication. This study investigated the role of inhibition in age-related off-topic verbosity (OTV). Inhibition consists of three functions: access, deletion, and restraint. The access function is responsible for preventing irrelevant information from accessing the attention center (pre-mechanism of inhibition); The deletion function is responsible for deleting previously relevant but currently irrelevant information from working memory, and the restraint function is responsible for restraining strong but inappropriate responses (post-mechanisms of inhibition). A referential communication task was used to determine whether OTV was influenced by the pre mechanism of inhibition. A self-involved event interview task was used to investigate the effect of the post-mechanisms of inhibition on OTV. Results showed that the OTV of the elderly participants was associated with an age related decline in the post-mechanisms of inhibition, while the OTV exhibited by young adults was most likely due to deficits in the pre-mechanism function of inhibition. This research contributed to fill gaps in the existing knowledge about the potential relationship between specific functions of inhibition and age related OTV. PMID- 27199792 TI - Using Distributional Statistics to Acquire Morphophonological Alternations: Evidence from Production and Perception. AB - Morphophonological alternations, such as the voicing alternation that arises in a morphological paradigm due to final-devoicing in Dutch, are notoriously difficult for children to acquire. This has previously been attributed to their unpredictability. In fact, the presence or absence of a voicing alternation is partly predictable if the phonological context of the word is taken into account, and adults have been shown to use this information (Ernestus and Baayen, 2003). This study investigates whether voicing alternations are predictable from the child's input, and whether children can make use of this information. A corpus study of child-directed speech establishes that the likelihood of a stem-final obstruent alternating is somewhat predictable on the basis of the phonological properties of the stem. In Experiment 1 Dutch 3-year-olds' production accuracy in a plural-elicitation task is shown to be sensitive to the distributional statistics. However, distributional properties do not play a role in children's sensitivity to mispronunciations of voicing in a Preferential Looking Task in Experiment 2. PMID- 27199795 TI - Minimal Interference from Possessor Phrases in the Production of Subject-Verb Agreement. AB - We explore the language production process by eliciting subject-verb agreement errors. Participants were asked to create complete sentences from sentence beginnings such as The elf's/elves' house with the tiny window/windows and The statue in the elf's/elves' gardens. These are subject noun phrases containing a head noun and controller of agreement (statue) and two nonheads, a "local noun" (window(s)/garden(s)), and a possessor noun (elf's/elves'). Past research has shown that a plural nonhead noun (an "attractor") within a subject noun phrase triggers the production of verb agreement errors, and further, that the nearer the attractor to the head noun, the greater the interference. This effect can be interpreted in terms of relative hierarchical distance from the head noun, or via a processing window account, which claims that during production, there is a window in which the head and modifying material may be co-active, and an attractor must be active at the same time as the head to give rise to errors. Using possessors attached at different heights within the same window, we are able to empirically distinguish these accounts. Possessors also allow us to explore two additional issues. First, case marking of local nouns has been shown to reduce agreement errors in languages with "rich" inflectional systems, and we explore whether English speakers attend to case. Secondly, formal syntactic analyses differ regarding the structural position of the possessive marker, and we distinguish them empirically with the relative magnitude of errors produced by possessors and local nouns. Our results show that, across the board, plural possessors are significantly less disruptive to the agreement process than plural local nouns. Proximity to the head noun matters: a possessor directly modifying the head noun induce a significant number of errors, but a possessor within a modifying prepositional phrase did not, though the local noun did. These findings suggest that proximity to a head noun is independent of a "processing window" effect. They also support a noun phrase-internal, case-like analysis of the structural position of the possessive ending and show that even speakers of inflectionally impoverished languages like English are sensitive to morphophonological case-like marking. PMID- 27199794 TI - Attitudes Toward Seeking Professional Psychological Help: Factor Structure and Socio-Demographic Predictors. AB - Attitudes toward seeking professional psychological help (ATSPPH) are complex. Help seeking preferences are influenced by various attitudinal and socio demographic factors and can often result in unmet needs, treatment gaps, and delays in help-seeking. The aims of the current study were to explore the factor structure of the ATSPPH short form (-SF) scale and determine whether any significant socio-demographic differences exist in terms of help-seeking attitudes. Data were extracted from a population-based survey conducted among Singapore residents aged 18-65 years. Respondents provided socio-demographic information and were administered the ATSPPH-SF. Weighted mean and standard error of the mean were calculated for continuous variables, and frequencies and percentages for categorical variables. Confirmatory factor analysis and exploratory factor analysis were performed to establish the validity of the factor structure of the ATSPPH-SF scale. Multivariable linear regressions were conducted to examine predictors of each of the ATSPPH-SF factors. The factor analysis revealed that the ATSPPH-SF formed three distinct dimensions: "Openness to seeking professional help," "Value in seeking professional help," and "Preference to cope on one's own." Multiple linear regression analyses showed that age, ethnicity, marital status, education, and income were significantly associated with the ATSPPH-SF factors. Population subgroups that were less open to or saw less value in seeking psychological help should be targeted via culturally appropriate education campaigns and tailored and supportive interventions. PMID- 27199796 TI - Web Ontologies to Categorialy Structure Reality: Representations of Human Emotional, Cognitive, and Motivational Processes. AB - This work presents a Web ontology for modeling and representation of the emotional, cognitive and motivational state of online learners, interacting with university systems for distance or blended education. The ontology is understood as a way to provide the required mechanisms to model reality and associate it to emotional responses, but without committing to a particular way of organizing these emotional responses. Knowledge representation for the contributed ontology is performed by using Web Ontology Language (OWL), a semantic web language designed to represent rich and complex knowledge about things, groups of things, and relations between things. OWL is a computational logic-based language such that computer programs can exploit knowledge expressed in OWL and also facilitates sharing and reusing knowledge using the global infrastructure of the Web. The proposed ontology has been tested in the field of Massive Open Online Courses (MOOCs) to check if it is capable of representing emotions and motivation of the students in this context of use. PMID- 27199797 TI - Pride, Shame, and Group Identification. AB - Self-conscious emotions such as shame and pride are emotions that typically focus on the self of the person who feels them. In other words, the intentional object of these emotions is assumed to be the subject that experiences them. Many reasons speak in its favor and yet this account seems to leave a question open: how to cash out those cases in which one genuinely feels ashamed or proud of what someone else does? This paper contends that such cases do not necessarily challenge the idea that shame and pride are about the emoting subject. Rather, we claim that some of the most paradigmatic scenarios of shame and pride induced by others can be accommodated by taking seriously the consideration that, in such cases, the subject "group-identifies" with the other. This is the idea that, in feeling these forms of shame or pride, the subject is conceiving of herself as a member of the same group as the subject acting shamefully or in an admirable way. In other words, these peculiar emotive responses are elicited in the subject insofar as, and to the extent that, she is (or sees herself as being) a member of a group - the group to which those who act shamefully or admirably also belong. By looking into the way in which the notion of group identification can allow for an account of hetero-induced shame and pride, this paper attempts to achieve a sort of mutual enlightenment that brings to light not only an important and generally neglected form of self-conscious emotions, but also relevant features of group identification. In particular, it generates evidence for the idea that group identification is a psychological process that the subject does not have to carry out intentionally in the sense that it is not necessarily triggered by the subject's conative states like desires or intentions. PMID- 27199798 TI - Comprehending Adverbs of Doubt and Certainty in Health Communication: A Multidimensional Scaling Approach. AB - This research explored the feasibility of using multidimensional scaling (MDS) analysis in novel combination with other techniques to study comprehension of epistemic adverbs expressing doubt and certainty (e.g., evidently, obviously, probably) as they relate to health communication in clinical settings. In Study 1, Australian English speakers performed a dissimilarity-rating task with sentence pairs containing the target stimuli, presented as "doctors' opinions." Ratings were analyzed using a combination of cultural consensus analysis (factor analysis across participants), weighted-data classical-MDS, and cluster analysis. Analyses revealed strong within-community consistency for a 3-dimensional semantic space solution that took into account individual differences, strong statistical acceptability of the MDS results in terms of stress and explained variance, and semantic configurations that were interpretable in terms of linguistic analyses of the target adverbs. The results confirmed the feasibility of using MDS in this context. Study 2 replicated the results with Canadian English speakers on the same task. Semantic analyses and stress decomposition analysis were performed on the Australian and Canadian data sets, revealing similarities and differences between the two groups. Overall, the results support using MDS to study comprehension of words critical for health communication, including in future studies, for example, second language speaking patients and/or practitioners. More broadly, the results indicate that the techniques described should be promising for comprehension studies in many communicative domains, in both clinical settings and beyond, and including those targeting other aspects of language and focusing on comparisons across different speech communities. PMID- 27199799 TI - Disentangling Metaphor from Context: An ERP Study. AB - A large body of electrophysiological literature showed that metaphor comprehension elicits two different event-related brain potential responses, namely the so-called N400 and P600 components. Yet most of these studies test metaphor in isolation while in natural conversation metaphors do not come out of the blue but embedded in linguistic and extra-linguistic context. This study aimed at assessing the role of context in the metaphor comprehension process. We recorded EEG activity while participants were presented with metaphors and equivalent literal expressions in a minimal context (Experiment 1) and in a supportive context where the word expressing the ground between the metaphor's topic and vehicle was made explicit (Experiment 2). The N400 effect was visible only in minimal context, whereas the P600 was visible both in the absence and in the presence of contextual cues. These findings suggest that the N400 observed for metaphor is related to contextual aspects, possibly indexing contextual expectations on upcoming words that guide lexical access and retrieval, while the P600 seems to reflect truly pragmatic interpretative processes needed to make sense of a metaphor and derive the speaker's meaning, also in the presence of contextual cues. In sum, previous information in the linguistic context biases toward a metaphorical interpretation but does not suppress interpretative pragmatic mechanisms to establish the intended meaning. PMID- 27199800 TI - The Complex Nature of Bilinguals' Language Usage Modulates Task-Switching Outcomes. AB - In view of inconsistent findings regarding bilingual advantages in executive functions (EF), we reviewed the literature to determine whether bilinguals' different language usage causes measureable changes in the shifting aspects of EF. By drawing on the theoretical framework of the adaptive control hypothesis which postulates a critical link between bilinguals' varying demands on language control and adaptive cognitive control (Green and Abutalebi, 2013), we examined three factors that characterize bilinguals' language-switching experience: (a) the interactional context of conversational exchanges, (b) frequency of language switching, and (c) typology of code-switching. We also examined whether methodological variations in previous task-switching studies modulate task specific demands on control processing and lead to inconsistencies in the literature. Our review demonstrates that not only methodological rigor but also a more finely grained, theory-based approach will be required to understand the cognitive consequences of bilinguals' varied linguistic practices in shifting EF. PMID- 27199801 TI - The Flexibility of Conceptual Pacts: Referring Expressions Dynamically Shift to Accommodate New Conceptualizations. AB - In a classic paper, Brennan and Clark argued that when interlocutors agree on a name for an object, they are forming a temporary agreement on how to conceptualize that object; that is, they are forming a conceptual pact. The literature on conceptual pacts has largely focused on the costs and benefits of breaking and maintaining lexical precedents, and the degree to which they might be partner-specific. The research presented here focuses on a question about conceptual pacts that has been largely neglected in the literature: To what extent are conceptual pacts specific to the local context of the interaction? If conceptual pacts are indeed temporary, then when the local context changes in ways that are accessible to participants, we would expect participants to seamlessly shift to referential expressions that reflect novel conceptualizations. Two experiments examined how referential forms change across context in collaborative, task-oriented dialog between naive participants. In Experiment 1, names for parts of an unknown object were established in an "item" identification stage (e.g., a shape that looked like a wrench was called "the wrench"). In a second "build" stage, that name was often supplanted by an object oriented name, e.g., the "leg." These changes happened abruptly and without negotiation. In Experiment 2, interlocutors manipulated clip art and more abstract tangram pictures in a "slider" puzzle to arrange the objects into a target configuration. On some trials moving an object revealed a picture that could be construed as a contrast competitor, e.g., a clip art picture of a camel after "the camel" had been negotiated as a name for a tangram shape, or vice versa. As would be expected, modification rates increased when a potential contrast was revealed. More strikingly, the degree to which a name had been negotiated or the frequency with which it had been used did not affect the likelihood that the revealed shape would be considered as a potential contrast. We find little evidence that names that are introduced as part of a conceptual pact persist when either the task goals or informational needs change. Rather, conceptual pacts are fluid temporary agreements. PMID- 27199803 TI - Event-Related Potentials and Emotion Processing in Child Psychopathology. AB - In recent years there has been increasing interest in the neural mechanisms underlying altered emotional processes in children and adolescents with psychopathology. This review provides a brief overview of the most up-to-date findings in the field of event-related potentials (ERPs) to facial and vocal emotional expressions in the most common child psychopathological conditions. In regards to externalizing behavior (i.e., ADHD, CD), ERP studies show enhanced early components to anger, reflecting enhanced sensory processing, followed by reductions in later components to anger, reflecting reduced cognitive-evaluative processing. In regards to internalizing behavior, research supports models of increased processing of threat stimuli especially at later more elaborate and effortful stages. Finally, in autism spectrum disorders abnormalities have been observed at early visual-perceptual stages of processing. An affective neuroscience framework for understanding child psychopathology can be valuable in elucidating underlying mechanisms and inform preventive intervention. PMID- 27199804 TI - Gender, Sexual Orientation, and Workplace Incivility: Who Is Most Targeted and Who Is Most Harmed? AB - Scholars have proposed that interpersonal workplace discrimination toward members of oppressed social groups has become covert and subtle rather than overt and explicit and that such experiences lead to negative outcomes for targets. The present study examined this proposition by examining experiences and consequences of workplace incivility-a seemingly harmless form of interpersonal maltreatment based on gender, sexual orientation, and their intersection. A sample of 1,300 academic faculty (52% male, 86% White) participated in an online survey study assessing their experiences of workplace incivility, job stress, job satisfaction, job identity centrality, and demographics. Results showed that sexual minority women reported the highest levels of workplace incivility. Findings also revealed that women reported lower job satisfaction than men and that heterosexuals reported higher job stress and lower job identity centrality than sexual minorities with higher levels of incivility. Thus, sexual minority status buffered the negative effects of incivility for sexual minorities. These findings point to the resiliency of sexual minorities in the face of interpersonal stressors at work. PMID- 27199802 TI - Emotional Processing and Attention Control Impairments in Children with Anxiety: An Integrative Review of Event-Related Potentials Findings. AB - Anxiety disorders in adults have been associated with biased processing of emotional information which may be due to a deficit in attentional control. This deficit leads to an hypervigilance and a selective attention toward threatening information. Event-related potentials (ERPs) have been used to study this topic in anxious adults. Similar biases have been reported in children with anxiety but researches investigating the ERPs components underpinning these biases are more scarce. However, the understanding of the neural correlates of attentional biases in anxious children seem quite important since they could play a role in the etiology and the maintenance of this disorder. This review summarizes the results of researches having used ERPs to index emotional processing and attention control in children suffering from anxiety. We will focus on the P1, indexing basic visual perceptual processing, the N2, thought to reflect cognitive control process, the P3 typically associated with response inhibition, and the late positive potential (LPP) that indicates sustained attention toward motivationally salient stimuli. We will also examine the error-related negativity (ERN) that indexes monitoring system for detecting errors. Electro-physiological studies generally reported increased amplitudes of these components in anxious children, even when they did not differ from typically developing children at a behavioral level. These results suggest diminished cognitive control that influences children's selective attention mechanisms toward threatening information. Theoretical perspectives and implications for future researches will be discussed in the framework of current models of childhood anxiety. PMID- 27199806 TI - Affect and Intellect in Judgments: Factors Which Determine Level of Evaluative Heterogeneity. PMID- 27199807 TI - Do the Best Teachers Get the Best Ratings? AB - We review recent studies that asked: do college students learn relatively more from teachers whom they rate highly on student evaluation forms? Recent studies measured learning at two-time points. When learning was measured with a test at the end of the course, the teachers who got the highest ratings were the ones who contributed the most to learning. But when learning was measured as performance in subsequent related courses, the teachers who had received relatively low ratings appeared to have been most effective. We speculate about why these effects occurred: making a course difficult in productive ways may decrease ratings but enhance learning. Despite their limitations, we do not suggest abandoning student ratings, but do recommend that student evaluation scores should not be the sole basis for evaluating college teaching and they should be recognized for what they are. PMID- 27199805 TI - The Grounded Expertise Components Approach in the Novel Area of Cryptic Crossword Solving. AB - This paper presents a relatively unexplored area of expertise research which focuses on the solving of British-style cryptic crossword puzzles. Unlike its American "straight-definition" counterparts, which are primarily semantically cued retrieval tasks, the British cryptic crossword is an exercise in code cracking detection work. Solvers learn to ignore the superficial "surface reading" of the clue, which is phrased to be deliberately misleading, and look instead for a grammatical set of coded instructions which, if executed precisely, will lead to the correct (and only) answer. Sample clues are set out to illustrate the task requirements and demands. Hypothesized aptitudes for the field might include high fluid intelligence, skill at quasi-algebraic puzzles, pattern matching, visuospatial manipulation, divergent thinking and breaking frame abilities. These skills are additional to the crystallized knowledge and word-retrieval demands which are also a feature of American crossword puzzles. The authors present results from an exploratory survey intended to identify the characteristics of the cryptic crossword solving population, and outline the impact of these results on the direction of their subsequent research. Survey results were strongly supportive of a number of hypothesized skill-sets and guided the selection of appropriate test content and research paradigms which formed the basis of an extensive research program to be reported elsewhere. The paper concludes by arguing the case for a more grounded approach to expertise studies, termed the Grounded Expertise Components Approach. In this, the design and scope of the empirical program flows from a detailed and objectively-based characterization of the research population at the very onset of the program. PMID- 27199808 TI - Landscape and Health: Connecting Psychology, Aesthetics, and Philosophy through the Concept of Affordance. AB - In this paper we address a frontier topic in the humanities, namely how the cultural and natural construction that we call landscape affects well-being and health. Following an updated review of evidence-based literature in the fields of medicine, psychology, and architecture, we propose a new theoretical framework called "processual landscape," which is able to explain both the health-landscape and the medical agency-structure binomial pairs. We provide a twofold analysis of landscape, from both the cultural and naturalist points of view: in order to take into account its relationship with health, the definition of landscape as a cultural product needs to be broadened through naturalization, grounding it in the scientific domain. Landscape cannot be distinguished from the ecological environment. For this reason, we naturalize the idea of landscape through the notion of affordance and Gibson's ecological psychology. In doing so, we stress the role of agency in the theory of perception and the health-landscape relationship. Since it is the result of continuous and co-creational interaction between the cultural agent, the biological agent and the affordances offered to the landscape perceiver, the processual landscape is, in our opinion, the most comprehensive framework for explaining the health-landscape relationship. The consequences of our framework are not only theoretical, but ethical also: insofar as health is greatly affected by landscape, this construction represents something more than just part of our heritage or a place to be preserved for the aesthetic pleasure it provides. Rather, we can talk about the right to landscape as something intrinsically linked to the well-being of present and future generations. PMID- 27199809 TI - Early Local Activity in Temporal Areas Reflects Graded Content of Visual Perception. AB - In visual cognitive neuroscience the debate on consciousness is focused on two major topics: the search for the neural correlates of the different properties of visual awareness and the controversy on the graded versus dichotomous nature of visual conscious experience. The aim of this study is to search for the possible neural correlates of different grades of visual awareness investigating the Event Related Potentials to reduced contrast visual stimuli whose perceptual clarity was rated on the four-point Perceptual Awareness Scale. Results revealed a left centro-parietal negative deflection (Visual Awareness Negativity; VAN) peaking at 280-320 ms from stimulus onset, related to the perceptual content of the stimulus, followed by a bilateral positive deflection (Late Positivity; LP) peaking at 510-550 ms over almost all electrodes, reflecting post-perceptual processes performed on such content. Interestingly, the amplitude of both deflections gradually increased as a function of visual awareness. Moreover, the intracranial generators of the phenomenal content (VAN) were found to be located in the left temporal lobe. The present data thus seem to suggest (1) that visual conscious experience is characterized by a gradual increase of perceived clarity at both behavioral and neural level and (2) that the actual content of perceptual experiences emerges from early local activation in temporal areas, without the need of later widespread frontal engagement. PMID- 27199810 TI - Chinese Preservice Teachers' Professional Identity Links with Education Program Performance: The Roles of Task Value Belief and Learning Motivations. AB - Professional identity is a key issue spanning the entirety of teachers' career development. Despite the abundance of existing research examining professional identity, its link with occupation-related behavior at the primary career stage (i.e., GPA in preservice education) and the potential process that underlies this association is still not fully understood. This study explored the professional identity of Chinese preservice teachers, and its links with task value belief, intrinsic learning motivation, extrinsic learning motivation, and performance in the education program. Grade-point average (GPA) of courses (both subject and pedagogy courses) was examined as an indicator of performance, and questionnaires were used to measure the remaining variables. Data from 606 preservice teachers in the first 3 years of a teacher-training program indicated that: (1) variables in this research were all significantly correlated with each other, except the correlation between intrinsic learning motivation and program performance; (2) professional identity was positively linked to task value belief, intrinsic and extrinsic learning motivations, and program performance in a structural equation model (SEM); (3) task value belief was positively linked to intrinsic and extrinsic learning motivation; (4) higher extrinsic (but not intrinsic) learning motivation was associated with increased program performance; and (5) task value belief and extrinsic learning motivation were significant mediators in the model. PMID- 27199812 TI - Linking Learning Contexts: The Relationship between Students' Civic and Political Experiences and Their Self-Regulation in School. AB - This paper considers the relationship between self-regulation strategies and youth civic and political experiences, assuming that out-of-school learning can foster metacognition. The study is based on a sample of 732 Portuguese students from grades 8 and 11. Results show that the quality of civic and political participation experiences, together with academic self-efficacy, are significant predictors of young people's self-regulation, particularly regarding cognitive and metacognitive strategies (elaboration and critical thinking). Such effects surpass even the weight of family cultural and school variables, such as the sense of school belonging. Therefore, we argue that the pedagogical value of non formal civic and political experiences is related to learning in formal pedagogical contexts. This is because civic and political participation with high developmental quality can stimulate higher-order cognitive engagement and, thus, contribute to the development of learning strategies that promote academic success. PMID- 27199813 TI - Editorial: Quantum Structures in Cognitive and Social Science. PMID- 27199811 TI - Screen Time on School Days and Risks for Psychiatric Symptoms and Self-Harm in Mainland Chinese Adolescents. AB - OBJECTIVE: To investigate associations of television and of video game or non educational computer use (VG/CU) exposure volumes in a typical school day with psychiatric symptoms and suicidal ideation/self-injurious behavior (self-harm), in mainland Chinese adolescents. METHODS: Secondary school pupils (N = 13,659; mean age: 15.18 +/- 1.89) from 10 urban areas sampled from different regions of mainland China were recruited. The subjects were divided into the following four screen exposure volume groups for television and VG/CU respectively based on a self-administered questionnaire: 0 h/day, >0 to <=1 h/day, >1 to <=2 h/day, and >2 h/day. Demographic and psychiatric symptoms were recorded for each respondent. Odds ratios (ORs) and 95% confidence intervals (CIs) for several types of psychological problems and self-harm were calculated. RESULTS: More than 2 h per school day television watching was associated with higher risk of depression in both boys (OR = 1.33, 95%CI: 1.02-1.73) and girls (OR = 1.62, 95%CI: 1.19-2.21), of anxiety in boys (OR = 1.43, 95%CI: 1.05-1.95), of general emotional, behavioral, and social problems (GEBSPs; OR = 1.55, 95%CI: 1.01-2.39), and of oppositional defiant problems (OR = 1.65, 95% CI: 1.09-2.50) in girls, compared with no television exposure. Conversely, television exposure of no more than 1 h per school day was associated with lower self-harm risk in boys (OR = 0.81, 95%CI: 0.67-0.99) compared with no television exposure. High school day VG/CU time (>2 h) compared with no VG/CU were associated with higher risks of anxiety (OR = 1.40, 95%CI: 1.06-1.86) and of attention deficit/hyperactivity problems (ADHPs; OR = 1.56, 95%CI: 1.02-2.38) in boys. And any school day VG/CU exposure was associated with higher risks of self-harm and all other psychiatric problems in boys and all psychiatric problems (including anxiety and ADHPs) in girls (ORs, 1.44-3.69), compared to no VG/CU exposure. CONCLUSION: For secondary school students, associations of psychiatric problems and self-harm were more strongly associated with exposure to VG/CU than with exposure to television. The findings suggest that VG/CU and television exposure on weekdays should be considered in psychiatric interventions for adolescents. PMID- 27199814 TI - Harm Avoidance and Self-Directedness Characterize Fibromyalgic Patients and the Symptom Severity. AB - OBJECTIVE: Evidence in the literature suggests peculiar personality traits for fibromyalgic (FM) patients, and it has been suggested that personality characteristics may be involved in patients' different symptomatic events and responses to treatment. The aim of the study is to investigate the personality characteristics of Italian FM patients and to explore the possibility of clustering them considering both personality traits and clinical characteristics. DESIGN: The study used a cross-sectional methodology and involved a control group. A self-assessment procedure was used for data gathering. The study included 87 female FM patients and 83 healthy females. Patients were approached and interviewed in person during a psychiatric consultation. Healthy people were recruited from general practices with previous telephone contact. MAIN OUTCOME MEASURES: Participants responded to the Hospital Anxiety and Depression Scale, the Temperament and Character Inventory, the Fibromyalgia Impact Questionnaire and the Short-Form-36 Health Survey. RESULTS: FM patients scored significantly different from healthy participants on the Harm avoidance (HA), Novelty seeking (NS) and Self-directedness (SD). Two clusters were identified: patients in Cluster1 (n = 37) had higher scores on HA and lower scores on RD, SD, and Cooperativeness and reported more serious fibromyalgia and more severe anxious depressive symptomatology than did patients in Cluster2 (n = 46). CONCLUSION: This study confirms the presence of certain personality traits in the FM population. In particular, high levels of HA and low levels of SD characterize a subgroup of FM patients with more severe anxious-depressive symptomatology. According to these findings, personality assessment could be useful in the diagnostic process to tailor therapeutic interventions to the personality characteristics. PMID- 27199815 TI - Mothers and Fathers with Binge Eating Disorder and Their 18-36 Months Old Children: A Longitudinal Study on Parent-Infant Interactions and Offspring's Emotional-Behavioral Profiles. AB - Maternal Binge Eating Disorder (BED) has been suggested to be associated with poor parent-infant interactions during feeding and with children's emotional and behavioral problems during infancy (Blissett and Haycraft, 2011). The role of fathers has received increasing consideration in recent years, yet the research has not focused on interactional patterns between fathers with BED and their children. The present study aimed to longitudinally investigate the influence of BED diagnosis, in one or both parents, on parent-infant feeding interactions and on children's emotional-behavioral functioning. 612 subjects (408 parents; 204 children), recruited in mental health services and pre-schools in Central Italy, were divided into four groups: Group 1 included families with both parents diagnosed with BED, Group 2 and 3 included families with one parent diagnosed with BED, Group 0 was a healthy control. The assessment took place at T1 (18 months of age of children) and T2 (36 months of age of children): feeding interactions were assessed through the Scale for the Assessment of Feeding Interactions (SVIA) while child emotional-behavioral functioning was evaluated with the Child Behavior Check-List (CBCL). When compared to healthy controls, the groups with one or both parents diagnosed with BED showed higher scores on the SVIA and on the CBCL internalizing and externalizing scales, indicating poorer adult-child feeding interactions and higher emotional-behavioral difficulties. A direct influence of parental psychiatric diagnosis on the quality of mother infant and father-infant interactions was also found, both at T1 and T2. Moreover, dyadic feeding interactions mediated the influence of parental diagnosis on children's psychological functioning. The presence of BED diagnosis in one or both parents seems to influence the severity of maladaptive parent infant exchanges during feeding and offspring's emotional-behavioral problems over time, consequently affecting different areas of children's psychological functioning. This is the first study to demonstrate the specific effects of maternal and paternal BED on infant development. These results could inform prevention and intervention programs in families with one or both parents diagnosed with BED. PMID- 27199816 TI - Coworking Spaces: A Source of Social Support for Independent Professionals. AB - Coworking spaces are shared office environments for independent professionals. Such spaces have been increasing rapidly throughout the world, and provide, in addition to basic business infrastructure, the opportunity for social interaction. This article explores social interaction in coworking spaces and reports the results of two studies. Study 1 (N = 69 coworkers) finds that social interaction in coworking spaces can take the form of social support. Study 2 further investigates social support among coworkers (N = 154 coworkers) and contrasts these results with those of social support among colleagues in traditional work organizations (N = 609). A moderated mediation model using time pressure and self-efficacy, based on the conservation of resources theory, is tested. Social support from both sources was positively related to performance satisfaction. Self-efficacy mediated this relationship in the employee sample, while in the coworking sample, self-efficacy only mediated the relationship between social support and performance satisfaction if time pressure was high. Thus, a mobilization of social support seems necessary in coworking spaces. We conclude that coworking spaces, as modern social work environments, should align flexible work infrastructure with well-constructed opportunities for social support. PMID- 27199817 TI - Job Embeddedness Demonstrates Incremental Validity When Predicting Turnover Intentions for Australian University Employees. AB - Job embeddedness is a construct that describes the manner in which employees can be enmeshed in their jobs, reducing their turnover intentions. Recent questions regarding the properties of quantitative job embeddedness measures, and their predictive utility, have been raised. Our study compared two competing reflective measures of job embeddedness, examining their convergent, criterion, and incremental validity, as a means of addressing these questions. Cross-sectional quantitative data from 246 Australian university employees (146 academic; 100 professional) was gathered. Our findings indicated that the two compared measures of job embeddedness were convergent when total scale scores were examined. Additionally, job embeddedness was capable of demonstrating criterion and incremental validity, predicting unique variance in turnover intention. However, this finding was not readily apparent with one of the compared job embeddedness measures, which demonstrated comparatively weaker evidence of validity. We discuss the theoretical and applied implications of these findings, noting that job embeddedness has a complementary place among established determinants of turnover intention. PMID- 27199818 TI - Grand Challenges in Environmental Psychology. PMID- 27199820 TI - Grouping Influences Output Interference in Short-term Memory: A Mixture Modeling Study. AB - Output interference is a source of forgetting induced by recalling. We investigated how grouping influences output interference in short-term memory. In Experiment 1, the participants were asked to remember four colored items. Those items were grouped by temporal coincidence as well as spatial alignment: two items were presented in the first memory array and two were presented in the second, and the items in both arrays were either vertically or horizontally aligned as well. The participants then performed two recall tasks in sequence by selecting a color presented at a cued location from a color wheel. In the same group condition, the participants reported both items from the same memory array; however, in the different-group condition, the participants reported one item from each memory array. We analyzed participant responses with a mixture model, which yielded two measures: guess rate and precision of recalled memories. The guess rate in the second recall was higher for the different-group condition than for the same-group condition; however, the memory precisions obtained for both conditions were similarly degraded in the second recall. In Experiment 2, we varied the probability of the same- and different-group conditions with a ratio of 3 to 7. We expected output interference to be higher in the same-group condition than in the different-group condition. This is because items of the other group are more likely to be probed in the second recall phase and, thus, protecting those items during the first recall phase leads to a better performance. Nevertheless, the same pattern of results was robustly reproduced, suggesting grouping shields the grouped items from output interference because of the secured accessibility. We discussed how grouping influences output interference. PMID- 27199821 TI - Once Dishonest, Always Dishonest? The Impact of Perceived Pervasiveness of Moral Evaluations of the Self on Motivation to Restore a Moral Reputation. AB - Four studies specify how moral evaluations of the self regulate behavior aimed at restoring a moral reputation. We propose that people care about evaluations of themselves as moral or immoral because these are perceived as more consequential than other types of information. Therefore people are more inclined to restore their image after being negatively evaluated in terms of morality rather than competence. Studies 1 and 2 revealed that moral information was perceived as having a more enduring impact on one's reputation, and was more strongly related to anticipate intra-group respect and self-views, than competence and sociability information. This perceived pervasiveness of moral (vs. competence) evaluations mediated intentions to justify and explain one's behavior (Study 3). Study 4 finally showed that being seen as lacking in morality elicited threat and coping responses, which induced subsequent tendencies to repair one's moral reputation. PMID- 27199822 TI - Assessing the Impact of Movement Consequences on the Development of Early Reaching in Infancy. AB - Prior research on infant reaching has shown that providing infants with repeated opportunities to reach for objects aids the emergence and progression of reaching behavior. This study investigated the effect of movement consequences on the process of learning to reach in pre-reaching infants. Thirty-five infants aged 2.9 months at the onset of the study were randomly assigned to 1 of 3 groups. Two groups received a 14-day intervention to distinct reaching tasks: (1) in a contingent group, a toy target moved and sounded upon contact only, and (2) in a continuous group, the toy moved and sounded continuously, independent of hand-toy contact. A third control group did not receive any intervention; this group's performance was assessed only on 2 days at a 15-day interval. Results revealed that infants in the contingent group made the most progress over time compared to the two other groups. Infants in this group made significantly more overall contacts with the sounding/moving toy, and they increased their rate of visually attended target contacts relative to non-visually attended target contacts compared to the continuous and control groups. Infants in the continuous group did not differ from the control group on the number of hand-toy contacts nor did they show a change in visually attended target versus non-visually attended target contacts ratio over time. However, they did show an increase in movement speed, presumably in an attempt to attain the moving toy. These findings highlight the importance of contingent movement consequences as a critical reinforcer for the selection of action and motor learning in early development. Through repeated opportunities to explore movement consequences, infants discover and select movements that are most successful to the task-at-hand. This study further demonstrates that distinct sensory-motor experiences can have a significant impact on developmental trajectories and can influence the skills young infants will discover through their interactions with their surroundings. PMID- 27199819 TI - Profiles of Recovery from Mood and Anxiety Disorders: A Person-Centered Exploration of People's Engagement in Self-Management. AB - CONTEXT: A shift toward person-centered care has been occurring in services provided to people with mood and anxiety disorders. Recovery is recognized as encompassing personal aspects in addition to clinical ones. Guidelines now recommend supporting people's engagement in self-management as a complementary recovery avenue. Yet the literature lacks evidence on how individualized combinations of self-management strategies used by people relate to their clinical and personal recovery indicators. OBJECTIVES: The aims of this study were to identify profiles underlying mental health recovery, describe the characteristics of participants corresponding to each profile, and examine the associations of profiles with criterion variables. METHOD: 149 people recovering from anxiety, depressive, or bipolar disorders completed questionnaires on self management, clinical recovery (symptom severity), personal recovery (positive mental health), and criterion variables (personal goal appraisal, social participation, self-care abilities, coping). RESULTS: Latent profile analysis (LPA) revealed three profiles. The Floundering profile included participants who rarely used self-management strategies and had moderately severe symptoms and the lowest positive mental health. The Flourishing profile was characterized by frequent use of self-empowerment strategies, the least severe symptoms, and the highest positive mental health. Participants in the Struggling profile engaged actively in several self-management strategies focused on symptom reduction and healthy lifestyle. They concomitantly reported high symptom severity and moderately high positive mental health. The study revealed that Floundering was associated with higher probabilities of being a man, being single, and having a low income. People in the Flourishing profile had the most favorable scores on criterion variables, supporting the profiles' construct validity. DISCUSSION: The mixed portrait of Struggling participants on recovery indicators suggests the relationship between health engagement and recovery is more intricate than anticipated. Practitioners should strive for a holistic understanding of their clients' self-management strategies and recovery indicators to provide support personalized to their profile. While people presenting risk factors would benefit from person-centered support, societal efforts are needed in the long term to reduce global health inequalities. The integration of constructs from diverse fields (patient-centered care, chronic illness, positive psychology) and the use of person-oriented analysis yielded new insights into people's engagement in their health and well-being. PMID- 27199823 TI - Intelligence, Cognition, and Language of Green Plants. AB - A summary definition of some 70 descriptions of intelligence provides a definition for all other organisms including plants that stresses fitness. Barbara McClintock, a plant biologist, posed the notion of the 'thoughtful cell' in her Nobel prize address. The systems structure necessary for a thoughtful cell is revealed by comparison of the interactome and connectome. The plant root cap, a group of some 200 cells that act holistically in responding to numerous signals, likely possesses a similar systems structure agreeing with Darwin's description of acting like the brain of a lower organism. Intelligent behavior requires assessment of different choices and taking the beneficial one. Decisions are constantly required to optimize the plant phenotype to a dynamic environment and the cambium is the assessing tissue diverting more or removing resources from different shoot and root branches through manipulation of vascular elements. Environmental awareness likely indicates consciousness. Spontaneity in plant behavior, ability to count to five and error correction indicate intention. Volatile organic compounds are used as signals in plant interactions and being complex in composition may be the equivalent of language accounting for self and alien recognition by individual plants. Game theory describes competitive interactions. Interactive and intelligent outcomes emerge from application of various games between plants themselves and interactions with microbes. Behavior profiting from experience, another simple definition of intelligence, requires both learning and memory and is indicated in the priming of herbivory, disease and abiotic stresses. PMID- 27199824 TI - The Categorical Distinction Between Targets and Distractors Facilitates Tracking in Multiple Identity Tracking Task. AB - This study investigates the tracking facilitation effect during categorical distinction between targets and distractors in the Multiple Identity Tracking task. We asked observers to track four targets in a total of eight moving objects, and manipulated categorical distinctions of targets and distractors across four experiments, with different combinations of inter-category and intra category differences. Results show that tracking performance was significantly better when the targets and distractors were inter-category different, compared to when the targets and distractors were identical or intra-category distinctive. As the inter-category distinction between targets and distractors narrowed, tracking performance improved, but the inter-category facilitation effect decreased. These results may indicate a category-based grouping effect: the observers organized the targets within the same semantic category into one group and made the targets more easily and accurately rediscovered when lost during tracking. Furthermore, the tracking facilitation of categorical distinction diminished when all the objects were inverted. This proved that besides their visual distinctiveness, objects' semantic category information also played an important role during tracking. PMID- 27199826 TI - Evidence for Trait Related Theory of Mind Impairment in First Episode Psychosis Patients and Its Relationship with Processing Speed: A 3 Year Follow-up Study. AB - This study aimed to confirm whether first-episode psychosis patients present a stable trait impairment in theory of mind (ToM) and to examine the potential relationship between ToM and clinical symptomatology and neurocognition. Patients with a first episode of psychosis (N = 160) and healthy controls (N = 159) were assessed with an extensive neuropsychological test battery, which included a mental state decoding task known as "The Reading the Mind in the Eyes" (Eyes test), at baseline and reassessed after 1 and 3 years. The clinical group performed below healthy controls on the Eyes test while not showing test-retest differences between baseline and follow-up administrations. Analyses revealed age, education and premorbid IQ as potential moderators. Poorer performance on the Eyes test was not linked to clinical symptomatology but was associated with greater neurocognitive deficit, particularly related to processing speed. The persistence of ToM deficits in patients suggests that there are trait related metalizing impairments in first episode psychosis. This study shows the influence of processing speed and moderator variables on efficient ToM. PMID- 27199825 TI - Students and Teachers Benefit from Mindfulness-Based Stress Reduction in a School Embedded Pilot Study. AB - OBJECTIVE: There is a research gap in studies that evaluate the effectiveness of a school-embedded mindfulness-based intervention for both students and teachers. To address this gap, the present pilot study reviews relevant literature and investigates whether students and teachers who participate in separate Mindfulness-Based Stress Reduction (MBSR) courses show improvements across a variety of psychological variables including areas of mental health and creativity. METHODS: The study applied a controlled waitlist design with three measurement points. A total of 29 students (n = 15 in the intervention and n = 14 in the waitlist group) and 29 teachers (n = 14 in the intervention and n = 15 in the waitlist group) completed questionnaires before and after the MBSR course. The intervention group was also assessed after a 4-month follow-up period. RESULTS: Relative to the control group, significant improvements in self-reported stress, self-regulation, school-specific self-efficacy and interpersonal problems were found among the students who participated in the MBSR course (p < 0.05, Cohens' d ranges from 0.62 to 0.68). Medium effect sizes on mindfulness, anxiety and creativity indicate a realistic potential in those areas. By contrast, teachers in the intervention group showed significantly higher self-reported mindfulness levels and reduced interpersonal problems compared to the control group(p < 0.05, Cohens' d = 0.66 and 0.42, respectively), with medium effect sizes on anxiety and emotion regulation. CONCLUSION: The present findings contribute to a growing body of studies investigating mindfulness in schools by discussing the similarities and differences in the effects of MBSR on students and teachers as well as stressing the importance of investigating interpersonal effects. PMID- 27199828 TI - Commentary: Cats prefer species-appropriate music. PMID- 27199827 TI - Preserved Intention Maintenance and Impaired Execution of Prospective Memory Responses in Schizophrenia: Evidence from an Event-based Prospective Memory Study. AB - Executive system dysfunction and impaired prospective memory (PM) are widely documented in schizophrenia. However, it is not yet clarified which components of PM function are impaired in this disorder. Two plausible target components are the maintenance of delayed intentions and the execution of PM responses. Furthermore, it is debated whether the impaired performance on frequently used executive tasks is associated with deficit in PM functions. The aim of our study was twofold. First, we aimed to investigate the specific processes involved in event-based PM function, mainly focusing on difference between maintenance of intention and execution of PM responses. Second, we aimed to unfold the possible connections between executive functions, clinical symptoms, and PM performance. An event-based PM paradigm was applied with three main conditions: baseline (with no expectation of PM stimuli, and without PM stimuli), expectation condition (participants were told that PM stimuli might occur, though none actually did), and execution condition (participants were told that PM stimuli might occur, and PM stimuli did occur). This procedure allowed us to separately investigate performances associated with intention maintenance and execution of PM responses. We assessed working memory and set-shifting executive functions by memory span tasks and by the Wisconsin Card Sorting Test (WCST), respectively. Twenty patients diagnosed with schizophrenia and 20 healthy control subjects (matched according to age and education) took part in the study. It was hypothesized that patients would manifest different levels of performance in the expectation and execution conditions of the PM task. Our results confirmed that the difference between baseline performance and performance in the execution condition (execution cost) was significantly larger for participants diagnosed with schizophrenia in comparison with matched healthy control group. However, this difference was not observed in the expectation condition. The PM performance in the execution condition was correlated with impaired executive functions in schizophrenia. Specifically, the size of execution cost positively correlated with percent of perseverative errors committed on WCST by the patient group. Our results suggest that maintenance of delayed intentions is unimpaired in schizophrenia, whereas the impairment in execution of PM responses is associated with set-shifting deficit. PMID- 27199829 TI - Age Differences in Visual-Auditory Self-Motion Perception during a Simulated Driving Task. AB - Recent evidence suggests that visual-auditory cue integration may change as a function of age such that integration is heightened among older adults. Our goal was to determine whether these changes in multisensory integration are also observed in the context of self-motion perception under realistic task constraints. Thus, we developed a simulated driving paradigm in which we provided older and younger adults with visual motion cues (i.e., optic flow) and systematically manipulated the presence or absence of congruent auditory cues to self-motion (i.e., engine, tire, and wind sounds). Results demonstrated that the presence or absence of congruent auditory input had different effects on older and younger adults. Both age groups demonstrated a reduction in speed variability when auditory cues were present compared to when they were absent, but older adults demonstrated a proportionally greater reduction in speed variability under combined sensory conditions. These results are consistent with evidence indicating that multisensory integration is heightened in older adults. Importantly, this study is the first to provide evidence to suggest that age differences in multisensory integration may generalize from simple stimulus detection tasks to the integration of the more complex and dynamic visual and auditory cues that are experienced during self-motion. PMID- 27199830 TI - How Does Adult Attachment Affect Human Recognition of Love-related and Sex related Stimuli: An ERP Study. AB - In the present study, we investigated the relationship among three emotion motivation systems (adult attachment, romantic love, and sex). We recorded event related potentials in 37 healthy volunteers who had experienced romantic love while they viewed SEX, LOVE, FRIEND, SPORT, and NEUTRAL images. We also measured adult attachment styles, level of passionate love and sexual attitudes. As expected, results showed that, firstly, response to love-related image-stimuli and sex-related image-stimuli on the electrophysiological data significantly different on N1, N2, and positive slow wave (PSW) components. Secondly, the different adult attachment styles affected individuals' recognition processing in response to love-related and sex-related images, especially, to sex-related images. Further analysis showed that voltages elicited by fearful attachment style individuals were significantly lower than voltages elicited by secure and dismissing attachment style individuals on sex-related images at frontal sites, on N1 and N2 components. Thirdly, from behavior data, we found that adult attachment styles were not significantly related to any dimension of sexual attitudes but were significantly related to passionate love scale (PLS) total points. Thus, the behavior results were not in line with the electrophysiological results. The present study proved that adult attachment styles might mediate individuals' lust and attraction systems. PMID- 27199831 TI - Altered Gray Matter Volume and White Matter Integrity in College Students with Mobile Phone Dependence. AB - Mobile phone dependence (MPD) is a behavioral addiction that has become an increasing public mental health issue. While previous research has explored some of the factors that may predict MPD, the underlying neural mechanisms of MPD have not been investigated yet. The current study aimed to explore the microstructural variations associated with MPD as measured with functional Magnetic Resonance Imaging (fMRI). Gray matter volume (GMV) and white matter (WM) integrity [four indices: fractional anisotropy (FA); mean diffusivity (MD); axial diffusivity (AD); and radial diffusivity (RD)] were calculated via voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) analysis, respectively. Sixty eight college students (42 female) were enrolled and separated into two groups [MPD group, N = 34; control group (CG), N = 34] based on Mobile Phone Addiction Index (MPAI) scale score. Trait impulsivity was also measured using the Barratt Impulsiveness Scale (BIS-11). In light of underlying trait impulsivity, results revealed decreased GMV in the MPD group relative to controls in regions such as the right superior frontal gyrus (sFG), right inferior frontal gyrus (iFG), and bilateral thalamus (Thal). In the MPD group, GMV in the above mentioned regions was negatively correlated with scores on the MPAI. Results also showed significantly less FA and AD measures of WM integrity in the MPD group relative to controls in bilateral hippocampal cingulum bundle fibers (CgH). Additionally, in the MPD group, FA of the CgH was also negatively correlated with scores on the MPAI. These findings provide the first morphological evidence of altered brain structure with mobile phone overuse, and may help to better understand the neural mechanisms of MPD in relation to other behavioral and substance addiction disorders. PMID- 27199832 TI - Adaptive Behavior and Development of Infants and Toddlers with Williams Syndrome. AB - Williams syndrome (WS) is a neurodevelopmental disorder that causes deficits in adaptive behavior, difficulties eating and sleeping, cognitive delays, and delayed development. Although researchers have conducted characterizations of children and adults with WS, less is known about young children with this disorder. This study characterizes the developmental and adaptive behavior features of 16 infants and toddlers with WS aged 3 months - 5 years. Data for this project was obtained from 2007 to 2014, and includes parent report data and standardized developmental testing. Thirty-one percent (31.3%) of parents reported that their infant/toddler with WS had sleeping problems and 58.3% reported feeding difficulties. Levels of adaptive behavior were in the Mildly Delayed range as measured by the Adaptive Behavior Assessment System, Second Edition. Self-care skills such as feeding or dressing oneself were significantly weaker than skills needed to function in the community, such as recognizing his/her home or throwing away trash. The difficulty with self-care skills is hypothesized to be related to the reported difficulties with eating and sleeping. Motor skills were significantly lower than both cognitive and language skills on the Bayley Scales of Infant and Toddler Development, Third Edition. The current study highlights the need for early intervention in these young children across all areas of development, particularly in self-care skills. PMID- 27199833 TI - Active Motor Training Has Long-term Effects on Infants' Object Exploration. AB - Long-term changes in infants' behavior as a result of active motor training were studied. Thirty-two infants completed three visits to the laboratory. At the first visit, infants were 3 months old and completed an object exploration assessment. Then the experimenter demonstrated the motor training procedures appropriate for the infant's experimental condition, and parents took home custom infant mittens (either sticky or non-sticky) and a bag of lightweight toys to practice with their infants. Over the course of the following 2 weeks, infants participated in 10 sessions of either active (sticky) or passive (non-sticky) mittens training at home with their parents. Infants who participated in active mittens training wore mittens with the palms covered in Velcro, allowing them to pick up and move around small toys. Infants who participated in passive mittens training wore non-sticky mittens, and their parents moved the toys through their visual fields on their behalf. After completing the training, infants returned to the lab for the second visit. At visit two, infants participated in another object exploration assessment as well as a reaching assessment. Parents returned the training materials to the lab at the second visit, and were told not to continue any specific training regimen from this point forward. Two months later, when infants were about 5.5 months of age, they returned to the lab for a third visit. At the third visit, infants completed the same two assessments as during the second visit. The results of this study indicate that infants who participated in active motor training engaged in more sophisticated object exploration when compared to infants who received passive training. These findings are consistent with others in the literature showing that active motor training at 3 months of age facilitates the processes of object exploration and engagement. The current results and others reveal that the effects of early experience can last long after training ceases. PMID- 27199834 TI - A Triadic Reflective-Impulsive-Interoceptive Awareness Model of General and Impulsive Information System Use: Behavioral Tests of Neuro-Cognitive Theory. AB - This study examines a behavioral tripartite model developed in the field of addiction, and applies it here to understanding general and impulsive information technology use. It suggests that technology use is driven by two information processing brain systems: reflective and impulsive, and that their effects on use are modulated by interoceptive awareness processes. The resultant reflective impulsive-interoceptive awareness model is tested in two behavioral studies. Both studies employ SEM techniques to time-lagged self-report data from n 1 = 300 and n 2 = 369 social networking site users. Study 1 demonstrated that temptations augment the effect of habit on technology use, and reduce the effect of satisfaction on use. Study 2 showed that temptations strengthen the effect of habit on impulsive technology use, and weaken the effect of behavioral expectations on impulsive technology use. Hence, the results consistently support the notion that information technology users' behaviors are influenced by reflective and impulsive information processing systems; and that the equilibrium of these systems is determined, at least in part, by one's temptations. These results can serve as a basis for understanding the etiology of modern day addictions. PMID- 27199836 TI - Students' Achievement Goals, Learning-Related Emotions and Academic Achievement. AB - In the present research, the recently proposed 3 * 2 model of achievement goals is tested and associations with achievement emotions and their joint influence on academic achievement are investigated. The study was conducted with 388 students using the 3 * 2 Achievement Goal Questionnaire including the six proposed goal constructs (task-approach, task-avoidance, self-approach, self-avoidance, other approach, other-avoidance) and the enjoyment and boredom scales from the Achievement Emotion Questionnaire. Exam grades were used as an indicator of academic achievement. Findings from CFAs provided strong support for the proposed structure of the 3 * 2 achievement goal model. Self-based goals, other-based goals and task-approach goals predicted enjoyment. Task-approach goals negatively predicted boredom. Task-approach and other-approach predicted achievement. The indirect effects of achievement goals through emotion variables on achievement were assessed using bias-corrected bootstrapping. No mediation effects were found. Implications for educational practice are discussed. PMID- 27199838 TI - Subjective Memory Ability and Long-Term Forgetting in Patients Referred for Neuropsychological Assessment. AB - It has been suggested that the memory complaints of patients who are not impaired on formal memory tests may reflect accelerated forgetting. We examined this hypothesis by comparing the 1-week delayed recall and recognition test performance of outpatients who were referred for neuropsychological assessment and who had normal memory performance during standard memory assessment with that of a non-patient control group. Both groups performed equally in verbal learning and delayed recall. However, after 1 week, the patients performed worse than controls on both recall and recognition tests. Although subjective memory ability predicted short-term memory function in patients, it did not predict long-term delayed forgetting rates in either the patients or controls. Thus, long-term delayed recall and recognition intervals provided no additional value to explain poor subjective memory ability in the absence of objective memory deficits. PMID- 27199835 TI - Neurocomputational Nosology: Malfunctions of Models and Mechanisms. AB - Executive dysfunctions, psychopathologies arising from problems in the control and regulation of behavior, can occur as a result of the faulty execution of formal information processing models or as a result of malfunctioning neural mechanisms. The models correspond to the formal descriptions of how signals in the environment must be transformed in order to behave adaptively, and the mechanisms correspond to the signal transformations that nervous systems implement in order to execute those cognitive functions. Mechanisms in the form of repeated patterns of neural dynamics execute information processing models. Two distinct modes of malfunction can occur when neural dynamics execute models of information processing. The processing models describing behavior may fail to be executed correctly by neural mechanisms. Or, the neural mechanisms may malfunction, failing to implement the right computation. As an example of malfunctioning models in executive cognition, purported failures of rule following can be understood as failures to appropriately execute a suite of processing models. As an example of malfunctioning mechanisms of executive cognition, maladaptive behavior resulting from dysfunction in the medial prefrontal cortex (mPFC) can be understood as failures in the signal transformations carried out therein. The purpose of these examples is to illustrate the potential benefits of considering models and mechanisms in the diagnosis and etiology of neuropsychological illness and dysfunction, especially disorders of executive cognition. PMID- 27199837 TI - Real-Time Monitoring of Psychotherapeutic Processes: Concept and Compliance. AB - OBJECTIVE: The feasibility of a high-frequency real-time monitoring approach to psychotherapy is outlined and tested for patients' compliance to evaluate its integration to everyday practice. Criteria concern the ecological momentary assessment, the assessment of therapy-related cognitions and emotions, equidistant time sampling, real-time nonlinear time series analysis, continuous participative process control by client and therapist, and the application of idiographic (person-specific) surveys. METHODS: The process-outcome monitoring is technically realized by an internet-based device for data collection and data analysis, the Synergetic Navigation System. Its feasibility is documented by a compliance study on 151 clients treated in an inpatient and a day-treatment clinic. RESULTS: We found high compliance rates (mean: 78.3%, median: 89.4%) amongst the respondents, independent of the severity of symptoms or the degree of impairment. Compared to other diagnoses, the compliance rate was lower in the group diagnosed with personality disorders. CONCLUSION: The results support the feasibility of high-frequency monitoring in routine psychotherapy settings. Daily collection of psychological surveys allows for the assessment of highly resolved, equidistant time series data which gives insight into the nonlinear qualities of therapeutic change processes (e.g., pattern transitions, critical instabilities). PMID- 27199841 TI - Does the Dark Triad of Personality Predict Corrupt Intention? The Mediating Role of Belief in Good Luck. AB - The current study is the first attempt to examine the association between the Dark Triad of personality (i.e., Machiavellianism, narcissism, and psychopathy) and corruption through a mediator-belief in good luck. Based on Ajzen's theory of planned behavior, we assumed that individuals with Dark Triad would be more likely to engage in corruption as a result of belief in good luck. In Study 1, a set of hypothetical scenarios was used to assess the bribe-offering intention and the corresponding belief in good luck. Results indicated that while the Dark Triad of personality positively predicted bribe-offering intention, it was mediated by the belief in good luck in gain-seeking. In Study 2, we presented participants with some hypothetical scenarios of bribe-taking and the corresponding belief in good luck. Findings revealed that the Dark Triad of personality was positively related to bribe-taking intention; the relationship between narcissism and bribe-taking intention, and that between psychopathy and bribe-taking intention was mediated by the belief in good luck in penalty avoidance. However, this belief in good luck did not mediate the relationship between Machiavellianism and bribe-taking intention. These results hold while controlling for demographic variables, dispositional optimism, and self-efficacy. Taken together, this study extended previous research by providing evidence that belief in good luck may be one of the reasons explaining why people with Dark Triad are more likely to engage in corruption regardless of the potential outcomes. Theoretical and practical implications were discussed. PMID- 27199839 TI - Not My Problem: Vicarious Conflict Adaptation with Human and Virtual Co-actors. AB - The Simon effect refers to an incompatibility between stimulus and response locations resulting in a conflict situation and, consequently, slower responses. Like other conflict effects, it is commonly reduced after repetitions, suggesting an executive control ability, which flexibly rewires cognitive processing and adapts to conflict. Interestingly, conflict is not necessarily individually defined: the Social Simon effect refers to a scenario where two people who share a task show a conflict effect where a single person does not. Recent studies showed these observations might converge into what could be called vicarious conflict adaptation, with evidence indicating that observing someone else's conflict may subsequently reduce one's own. While plausible, there is reason for doubt: both the social aspect of the Simon Effect, and the degree to which executive control accounts for the conflict adaptation effect, have become foci of debate in recent studies. Here, we present two experiments that were designed to test the social dimension of the effect by varying the social relationship between the actor and the co-actor. In Experiment 1, participants performed a conflict task with a virtual co-actor, while the actor-observer relationship was manipulated as a function of the similarity between response modalities. In Experiment 2, the same task was performed both with a virtual and with a human co actor, while heart-rate measurements were taken to measure the impact of observed conflict on autonomous activity. While both experiments replicated the interpersonal conflict adaptation effects, neither showed evidence of the critical social dimension. We consider the findings as demonstrating that vicarious conflict adaptation does not rely on the social relationship between the actor and co-actor. PMID- 27199840 TI - Supporting Sustainable Food Consumption: Mental Contrasting with Implementation Intentions (MCII) Aligns Intentions and Behavior. AB - With growing awareness that sustainable consumption is important for quality of life on earth, many individuals intend to act more sustainably. In this regard, interest in reducing meat consumption is on the rise. However, people often do not translate intentions into actual behavior change. To address this intention behavior gap, we tested the self-regulation strategy of mental contrasting with implementation intentions (MCII). Here, people identify and imagine a desired future and current obstacles standing in its way. They address the obstacles with if-then plans specifying when, where, and how to act differently. In a 5-week randomized controlled experimental study, we compared an information + MCII intervention with an information-only control intervention. As hypothesized, only MCII participants' intention of reducing their meat consumption was predictive of their actual reduction, while no correspondence between intention and behavior change was found for control participants. Participants with a moderate to strong intention to reduce their meat consumption reduced it more in the MCII than in the control condition. Thus, MCII helped to narrow the intention-behavior gap and supported behavior change for those holding moderate and strong respective intentions. PMID- 27199842 TI - The Effects of Activating the Money Concept on Perseverance and the Preference for Delayed Gratification in Children. AB - The psychological model of thinking about money assumes that implicit reminders of money lead to self-sufficient motivation. Previous research has demonstrated that children react to money in similar ways to adults. The priming of young children with money related concepts or images has negatively affected their social behavior and social preferences, leading them to make more individualist and less pro-social choices and be less willing to help others. The aim of this research was to investigate the positive influence of money activation on children's behavior. The participants were 6-8 year old children who do not yet fully understand the instrumental function of money due to their young age. Two experimental studies were performed, the first of which analyzed the effect of perseverance and performance on a challenging task and the second investigated preferences with respect to delaying gratification. Sixty-one children aged 6 took part in the first study and forty-six scout camp participants 6-8 years of age were involved in the second experiment. The results support the hypotheses concerning the effects of money activation stating that (1) money activation influences children's perseverance and effectiveness in difficult individual tasks, and that (2) it increases children's preferences for delayed gratification. These results suggest that money has a symbolic power which may exert both positive and negative effects on children's behavior. Since children between the ages of 6 and 8 do not understand the instrumental function of money fully, certain symbolic meanings of money may have been responsible for the money priming effects. The findings suggest that the symbolic function of money is more primal than its instrumental function and that it probably develops at an earlier stage in life. PMID- 27199843 TI - The Experiment Factory: Standardizing Behavioral Experiments. AB - The administration of behavioral and experimental paradigms for psychology research is hindered by lack of a coordinated effort to develop and deploy standardized paradigms. While several frameworks (Mason and Suri, 2011; McDonnell et al., 2012; de Leeuw, 2015; Lange et al., 2015) have provided infrastructure and methods for individual research groups to develop paradigms, missing is a coordinated effort to develop paradigms linked with a system to easily deploy them. This disorganization leads to redundancy in development, divergent implementations of conceptually identical tasks, disorganized and error-prone code lacking documentation, and difficulty in replication. The ongoing reproducibility crisis in psychology and neuroscience research (Baker, 2015; Open Science Collaboration, 2015) highlights the urgency of this challenge: reproducible research in behavioral psychology is conditional on deployment of equivalent experiments. A large, accessible repository of experiments for researchers to develop collaboratively is most efficiently accomplished through an open source framework. Here we present the Experiment Factory, an open source framework for the development and deployment of web-based experiments. The modular infrastructure includes experiments, virtual machines for local or cloud deployment, and an application to drive these components and provide developers with functions and tools for further extension. We release this infrastructure with a deployment (http://www.expfactory.org) that researchers are currently using to run a set of over 80 standardized web-based experiments on Amazon Mechanical Turk. By providing open source tools for both deployment and development, this novel infrastructure holds promise to bring reproducibility to the administration of experiments, and accelerate scientific progress by providing a shared community resource of psychological paradigms. PMID- 27199844 TI - Overestimation of the Subjective Experience of Time in Social Anxiety: Effects of Facial Expression, Gaze Direction, and Time Course. AB - It is known that threatening stimuli increase emotional arousal, resulting in overestimating the subjective experience of passing time. Moreover, facial expressions and gaze direction interact to create socially threatening situations in people with social anxiety. The present study investigated the effect of social anxiety on the perceived duration of observing emotional faces with a direct or an averted gaze. Participants were divided into high, medium and low social anxiety groups based on social anxiety inventory scores. Participants then performed a temporal bisection task. Participants with high social anxiety provided larger overestimates for neutral faces with an averted gaze than those with low social anxiety in the second half of the task, whereas these differences were not found for angry face with direct and averted gaze. These results suggest that people with social anxiety perceive the duration of threatening situations as being longer than true durations based on objectively measured time. PMID- 27199845 TI - Relations between Spatial Distribution, Social Affiliations and Dominance Hierarchy in a Semi-Free Mandrill Population. AB - Although there exist advantages to group-living in comparison to a solitary lifestyle, costs and gains of group-living may be unequally distributed among group members. Predation risk, vigilance levels and food intake may be unevenly distributed across group spatial geometry and certain within-group spatial positions may be more or less advantageous depending on the spatial distribution of these factors. In species characterized with dominance hierarchy, high-ranking individuals are commonly observed in advantageous spatial position. However, in complex social systems, individuals can develop affiliative relationships that may balance the effect of dominance relationships in individual's spatial distribution. The objective of the present study is to investigate how the group spatial distribution of a semi-free ranging colony of Mandrills relates to its social organization. Using spatial observations in an area surrounding the feeding zone, we tested the three following hypothesis: (1) does dominance hierarchy explain being observed in proximity or far from a food patch? (2) Do affiliative associations also explain being observed in proximity or far from a food patch? (3) Do the differences in rank in the group hierarchy explain being co-observed in proximity of a food patch? Our results showed that high-ranking individuals were more observed in proximity of the feeding zone while low-ranking individuals were more observed at the boundaries of the observation area. Furthermore, we observed that affiliative relationships were also associated with individual spatial distributions and explain more of the total variance of the spatial distribution in comparison with dominance hierarchy. Finally, we found that individuals observed at a same moment in proximity of the feeding zone were more likely to be distant in the hierarchy while controlling for maternal kinship, age and sex similarity. This study brings some elements about how affiliative networks and dominance hierarchy are related to spatial positions in primates. PMID- 27199846 TI - When Pain Brings Gain: Soccer Players Behavior and Admissions Suggest Feigning Injury to Maintain a Favorable Scoreline. AB - The rules of soccer dictate that play, once halted, cannot continue if a player is injured. Players may take advantage of this rule by feigning injury to preserve beneficial match positions. Thirty Euro 2008 matches, 90 Premier League matches and 63 World Cup 2010 matches were reviewed for the timing and severity of injuries. The number of injuries was compared between teams that benefited from stopping the game and those that did not benefit. The number of low-level injuries, not resulting in substitution or subsequent problems, was directly compared for Benefit and Non-Benefit teams for each 15-min period following kick off. Statistical significance was assessed using appropriate non-parametric tests. In addition, seven current players and three managers were interviewed and were asked about feigning injury. Teams that benefited from game stoppages suffered significantly more minor injuries in the last 15 min of matches compared with those that did not benefit. Four of the players directly admitted feigning injury. When it is beneficial, soccer players can and do successfully feign injury to stop the game. Consequently it is possible that others might also successfully feign injury, pain or disease when motivated to do so. PMID- 27199847 TI - Effects of a Fragmented View of One's Partner on Interpersonal Coordination in Dance. AB - In this study we investigated the effects of a mirror-mediated, partial view of one's dance partner on interpersonal coordination in dance duets. Fourteen participant pairs (dyads) were asked to perform a reflectionally-symmetric eight segment dance-relevant arm movement sequence in two visual conditions: with one dancer facing the mirror and providing a partial view on the dance partner, or both dancers facing back to back with, for both dancers, no view on one's partner. During an eight-count beat-preparation phase, the task was paced via a metronome at three TEMPI; 1.6, 1.9, and 2.3 Hz, which was subsequently removed after which the movement sequence continued in silence. Interpersonal coordination was assessed using two tri-axial wireless accelerometers, one fixed to each dancer, that allowed the off-line kinematic analyses of dyad correlation, mean relative phase and mean standard deviation of relative phase of the up-down movements of (one of) the hands of the two dancers. In addition, two independent raters estimated the realized movement frequencies and percentage of the trial duration that the dancers moved in sync. Repeated measure ANOVAs revealed systematic effects of tempo on the performance measures, a positive effect of the use of the mirror on the coordination of the dancers' movements but no facilitating effect of the mirror on the dancers' synchronization. Overall, the results support the contention that when dancing to an internalized rhythmic beat the use of a mirror provides an ecological means to stabilize interpersonal coordination in dance duets without an effect on synchronization. PMID- 27199848 TI - The Impact of Interpersonal Discrimination and Stress on Health and Performance for Early Career STEM Academicians. AB - The present study examines the consequences of perceived interpersonal discrimination on stress, health, and performance in a sample of 210 science, technology, engineering, and mathematics (STEM) academicians. Using a path model, we test the relation that perceived interpersonal discrimination has on stress and the relation of stress to physical health maladies and on current and future performance. In so doing, we assess the link between discrimination and decrements in performance over time. Additionally, we test supervisor social support as a moderator of the discrimination-stress relation. Findings support relations between perceived interpersonal discrimination and stress, which in turn relates to declines in physical health and performance outcomes. Moreover, supervisory support is shown to mitigate the influence of interpersonal discrimination on stress in STEM academicians. PMID- 27199849 TI - Cross-Linguistic Influence in the Bilingual Mental Lexicon: Evidence of Cognate Effects in the Phonetic Production and Processing of a Vowel Contrast. AB - The present study examines cognate effects in the phonetic production and processing of the Catalan back mid-vowel contrast (/o/-/o/) by 24 early and highly proficient Spanish-Catalan bilinguals in Majorca (Spain). Participants completed a picture-naming task and a forced-choice lexical decision task in which they were presented with either words (e.g., /bosk/ "forest") or non-words based on real words, but with the alternate mid-vowel pair in stressed position ((*)/bosk/). The same cognate and non-cognate lexical items were included in the production and lexical decision experiments. The results indicate that even though these early bilinguals maintained the back mid-vowel contrast in their productions, they had great difficulties identifying non-words and real words based on the identity of the Catalan mid-vowel. The analyses revealed language dominance and cognate effects: Spanish-dominants exhibited higher error rates than Catalan-dominants, and production and lexical decision accuracy were also affected by cognate status. The present study contributes to the discussion of the organization of early bilinguals' dominant and non-dominant sound systems, and proposes that exemplar theoretic approaches can be extended to include bilingual lexical connections that account for the interactions between the phonetic and lexical levels of early bilingual individuals. PMID- 27199850 TI - Modeling of Causes of Sina Weibo Continuance Intention with Mediation of Gender Effects. AB - Sina Weibo is a Twitter-like social networking site and one of the most popular microblogging services in China. This study aims to examine the factors that influence the intentions of users to continue using this site. This paper synthesizes the expectation confirmation model, constructs of habit and perceived critical mass, and the gender effect to construct a theoretical model to explain and predict these user intentions. The model is then tested via an online survey of 498 Sina Weibo users and partial least squares (PLS) modeling. The results indicate that the continuance intention of users is directly predicted by their perceived usefulness of the service (beta = 0.299), their satisfaction (beta = 0.208), and their habits (beta = 0.389), which jointly explain 65.9% of the variance in intention. In addition to the effects of these predictors on the continuance intentions of Sina Weibo users, an assessment of the moderating effect of gender suggests that habit plays a more important role for females than for males in continuance intention, but perceived usefulness seems to be more important for males than for females. The implications of these findings are then discussed. PMID- 27199851 TI - Commentary: "How Much is that Player in the Window? The One with the Early Birthday?" Relative Age Influences the Value of the Best Soccer Players, but Not the Best Businesspeople. PMID- 27199852 TI - Relations between Temperament, Sensory Processing, and Motor Coordination in 3 Year-Old Children. AB - Poor motor skills and differences in sensory processing have been noted as behavioral markers of common neurodevelopmental disorders. A total of 171 healthy children (81 girls, 90 boys) were investigated at age 3 to examine relations between temperament, sensory processing, and motor coordination. Using the Japanese versions of the Children's Behavior Questionnaire (CBQ), the Sensory Profile (SP-J), and the Little Developmental Coordination Disorder Questionnaire (LDCDQ), this study examines an expanded model based on Rothbart's three-factor temperamental theory (surgency, negative affect, effortful control) through covariance structure analysis. The results indicate that effortful control affects both sensory processing and motor coordination. The subscale of the LDCDQ, control during movement, is also influenced by surgency, while temperamental negative affect and surgency each have an effect on subscales of the SP-J. PMID- 27199854 TI - Competition between Cognitive Control and Encapsulated, Unconscious Inferences: Are Aha-Experiences Special? PMID- 27199853 TI - Compulsive Buying Behavior: Characteristics of Comorbidity with Gambling Disorder. AB - Compulsive buying behavior (CBB) has begun to be recognized as a condition worthy of attention by clinicians and researchers. Studies on the commonalities between CBB and other behavioral addictions such as gambling disorder (GD) exist in the literature, but additional research is needed to assess the frequency and clinical relevance of the comorbidity of CBB and GD. The aim of the study was to estimate the point-prevalence of CBB+GD in a clinical setting. Data corresponded to n = 3221 treatment-seeking patients who met criteria for CBB or GD at a public hospital unit specialized in treating behavioral addictions. Three groups were compared: only-CBB (n = 127), only-GD (n = 3118) and comorbid CBB+GD (n = 24). Prevalence for the co-occurrence of CBB+GD was 0.75%. In the stratum of patients with GD, GD+CBB comorbidity obtained relatively low point prevalence (0.77%), while in the subsample of CBB patients the estimated prevalence of comorbid GD was relatively high (18.9%). CBB+GD comorbidity was characterized by lower prevalence of single patients, higher risk of other behavioral addictions (sex, gaming or internet), older age and age of onset. CBB+GD registered a higher proportion of women compared to only-GD (37.5 vs. 10.0%) but a higher proportion of men compared to only-CBB (62.5 vs. 24.4%). Compared to only-GD patients, the simultaneous presence of CBB+GD was associated with increased psychopathology and dysfunctional levels of harm avoidance. This study provides empirical evidence to better understand CBB, GD and their co-occurrence. Future research should help delineate the processes through which people acquire and develop this comorbidity. PMID- 27199855 TI - Effects of Suprasegmental Phonological Alternations on Early Word Recognition: Evidence from Tone Sandhi. AB - Early language acquisition is potentially complicated by the presence of many sources of variability in the speech signal. A frequent example of variability is phonological alternations, which can lead to context-driven changes in the realization of a word. The aim of the current study was to investigate effects of a highly frequent yet scarcely researched type of suprasegmental phonological alternation - tone Sandhi - on early spoken word recognition. The tone Sandhi rule investigated herein involves a tone change of the first syllable in a disyllabic unit. In accordance with third tone Sandhi, when two dipping tone syllables are juxtaposed in connected speech, the first syllable is dissimilated to a high rising tone. For example, 'flour mill' (unaltered pre-Sandhi form [(214) (214)]) undergoes tonal alternation resulting in the altered post-Sandhi form [(35) (214)]. In the current study, preschoolers' sensitivity to the effects of tone Sandhi when processing familiar words was investigated via a preferential looking paradigm. Words varied in their phonological form: one set of words was labeled with a phonological alternation due to Sandhi (Post Sandhi), one set of words was labeled with an unaltered Sandhi form (Pre Sandhi), one set consisted of non Sandhi words (Correct Pronunciation, and one set were labeled with a tonal alternation not associated with Sandhi rules (Mispronunciation). Post-Sandhi forms and correct pronunciations were associated with visual referents with comparable strength, with only a subtle processing cost observed for post-Sandhi forms in the time course of lexical selection. Likewise, pre-Sandhi forms and true mispronunciations were rejected as labels for visual references with comparable strength, with only subtle differences observed in the time course of lexical selection. Findings are discussed in terms of their impact on prevailing theories of lexical representation. PMID- 27199856 TI - Editorial: From Is to Ought: The Place of Normative Models in the Study of Human Thought. PMID- 27199857 TI - Comparing the Effectiveness of Individual Coaching, Self-Coaching, and Group Training: How Leadership Makes the Difference. AB - Few empirical studies have used a randomized controlled design to evaluate the impact of coaching, and there are even fewer that have compared coaching with other interventions. In the current field study, we investigated the relative effectiveness of coaching as an intervention to reduce procrastination. In a randomized controlled study, participants (N = 84) were assigned to an individual coaching, a self-coaching, a group training, or a control group condition. Results indicate that individual coaching and group training were effective in reducing procrastination and facilitating goal attainment. Individual coaching created a high degree of satisfaction and was superior in helping participants attaining their goals, whereas group training successfully promoted the acquisition of relevant knowledge. The results for the self-coaching condition show that independently performing exercises without being supported by a coach is not sufficient for high goal attainment. Moreover, mediation analysis show that a coach's transformational and transactional leadership behavior influenced participants' perceived autonomy support and intrinsic motivation, resulting in beneficial coaching outcomes. The results may guide the selection of appropriate human resource development methods: If there is a general need to systematically prepare employees to perform on specific tasks, group training seems appropriate due to lower costs. However, when certain aspects of working conditions or individual development goals are paramount, coaching might be indicated. However, further research is needed to compare the relative effectiveness of coaching with other interventions in different contexts. PMID- 27199859 TI - Animal Assisted Therapy (AAT) Program As a Useful Adjunct to Conventional Psychosocial Rehabilitation for Patients with Schizophrenia: Results of a Small scale Randomized Controlled Trial. AB - Currently, one of the main objectives of human-animal interaction research is to demonstrate the benefits of animal assisted therapy (AAT) for specific profiles of patients or participants. The aim of this study is to assess the effect of an AAT program as an adjunct to a conventional 6-month psychosocial rehabilitation program for people with schizophrenia. Our hypothesis is that the inclusion of AAT into psychosocial rehabilitation would contribute positively to the impact of the overall program on symptomology and quality of life, and that AAT would be a positive experience for patients. To test these hypotheses, we compared pre program with post-program scores for the Positive and Negative Syndrome Scale (PANSS) and the EuroQoL-5 dimensions questionnaire (EuroQol-5D), pre-session with post-session salivary cortisol and alpha-amylase for the last four AAT sessions, and adherence rates between different elements of the program. We conducted a randomized, controlled study in a psychiatric care center in Spain. Twenty-two institutionalized patients with chronic schizophrenia completed the 6-month rehabilitation program, which included individual psychotherapy, group therapy, a functional program (intended to improve daily functioning), a community program (intended to facilitate community reintegration) and a family program. Each member of the control group (n = 8) participated in one activity from a range of therapeutic activities that were part of the functional program. In place of this functional program activity, the AAT-treatment group (n = 14) participated in twice-weekly 1-h sessions of AAT. All participants received the same weekly total number of hours of rehabilitation. At the end of the program, both groups (control and AAT-treatment) showed significant improvements in positive and overall symptomatology, as measured with PANSS, but only the AAT-treatment group showed a significant improvement in negative symptomatology. Adherence to the AAT treatment was significantly higher than overall adherence to the control group's functional rehabilitation activities. Cortisol level was significantly reduced after participating in an AAT session, which could indicate that interaction with the therapy dogs reduced stress. In conclusion, the results of this small-scale RCT suggest that AAT could be considered a useful adjunct to conventional psychosocial rehabilitation for people with schizophrenia. PMID- 27199858 TI - Nogo Stimuli Do Not Receive More Attentional Suppression or Response Inhibition than Neutral Stimuli: Evidence from the N2pc, PD, and N2 Components in a Spatial Cueing Paradigm. AB - It has been claimed that stimuli sharing the color of the nogo-target are suppressed because of the strong incentive to not process the nogo-target, but we failed to replicate this finding. Participants searched for a color singleton in the target display and indicated its shape when it was in the go color. If the color singleton in the target display was in the nogo color, they had to withhold the response. The target display was preceded by a cue display that also contained a color singleton (the cue). The cue was either in the color of the go or nogo target, or it was in an unrelated, neutral color. With cues in the go color, reaction times were shorter when the cue appeared at the same location as the target compared to when it appeared at a different location. Also, electrophysiological recordings showed that an index of attentional selection, the N2pc, was elicited by go cues. Surprisingly, we failed to replicate cueing costs for cues in the nogo color that were originally reported by Anderson and Folk (2012). Consistently, we also failed to find an electrophysiological index of attentional suppression (the PD) for cues in the nogo color. Further, fronto central event-related potentials to the cue display showed the same negativity for nogo and neutral stimuli relative to go stimuli, which is at odds with response inhibition and conflict monitoring accounts of the Nogo-N2. Thus, the modified cueing paradigm employed here provides little evidence that features associated with nogo-targets are suppressed at the level of attention or response selection. Rather, nogo-stimuli are efficiently ignored and attention is focused on features that require a response. PMID- 27199860 TI - An Internal Focus Leads to Longer Quiet Eye Durations in Novice Dart Players. AB - While the benefits of both an external focus of attention (FOA) and of a longer quiet eye (QE) duration have been well researched in a wide range of sporting activities, little is known about the interaction of these two phenomena and how a potential interaction might influence performance. It was this study's aim to investigate the interaction and potential effect on performance by using typical FOA instructions in a dart throwing task and examining both the QE and performance outcome. The results replicate neither the benefit of an external FOA nor the benefit of a longer QE duration. However, an interaction was observed, as QE was prolonged by an earlier onset and later offset in the internal focus condition only. As the typical effect of a performance benefit due to an external focus could not be replicated, the interaction must be interpreted with caution. The results are discussed and interpreted in light of the inhibition hypothesis and possible avenues for future research are suggested. PMID- 27199861 TI - Temporal Learning and Rhythmic Responding: No Reduction in the Proportion Easy Effect with Variable Response-Stimulus Intervals. AB - The present report further investigates the proportion easy effect, a conflict free version of the proportion congruent effect. In the proportion easy paradigm, it is observed that the difference in performance between easy (high contrast) and hard (low contrast) items is smaller in a task with mostly hard items relative to a task with mostly easy items. This effect has been interpreted as evidence for temporal learning: participants learn a faster pace (i.e., rhythm of responding) in the mostly easy context, which boosts the contrast effect, and a slower pace in the mostly hard context. In the present experiment, intervals between trials were either fixed or randomly varied from trial to trial. Interestingly, the proportion easy effect was still present with variable intervals. These data suggest that participants do not learn the regularity in timing from one response to the next (which was highly inconsistent with variable intervals). As one alternative, participants might be learning the intervals between stimulus onset and responses, which were not manipulated. They could then use this learned timing information to prepare for responding at the anticipated time, resulting in rhythmic responding. The results further imply that variable response-stimulus intervals are insufficient for controlling for rhythmic biases. PMID- 27199862 TI - Music Influences Hedonic and Taste Ratings in Beer. AB - The research presented here focuses on the influence of background music on the beer-tasting experience. An experiment is reported in which different groups of customers tasted a beer under three different conditions (N = 231). The control group was presented with an unlabeled beer, the second group with a labeled beer, and the third group with a labeled beer together with a customized sonic cue (a short clip from an existing song). In general, the beer-tasting experience was rated as more enjoyable with music than when the tasting was conducted in silence. In particular, those who were familiar with the band that had composed the song, liked the beer more after having tasted it while listening to the song, than those who knew the band, but only saw the label while tasting. These results support the idea that customized sound-tasting experiences can complement the process of developing novel beverage (and presumably also food) events. We suggest that involving musicians and researchers alongside brewers in the process of beer development, offers an interesting model for future development. Finally, we discuss the role of attention in sound-tasting experiences, and the importance that a positive hedonic reaction toward a song can have for the ensuing tasting experience. PMID- 27199863 TI - Different Sources of Threat on Math Performance for Girls and Boys: The Role of Stereotypic and Idiosyncratic Knowledge. PMID- 27199864 TI - Happy Family Kitchen II: A Cluster Randomized Controlled Trial of a Community Based Family Intervention for Enhancing Family Communication and Well-being in Hong Kong. AB - Long working hours and stressful urban lifestyles pose major challenges to family communication and well-being in Hong Kong. A community-based family intervention derived from a positive psychology framework, by using cooking and dining as a platform, was developed for improving family communication and well-being. Social workers and teachers from 31 social service units and schools in collaboration with an academic partner organized and conducted the intervention programs for 2,070 individuals from 973 families in a deprived district in Hong Kong. The participants were randomly assigned into the intervention or control group in a cluster randomized controlled trial (cRCT). The core intervention covered one of five positive psychology themes: joy, gratitude, flow, savoring, and listening. Assessments at pre-intervention, immediate post-intervention, and 4 and 12 weeks post-intervention showed improved family communication and well-being with sustainable effects up to 12 weeks. Positive changes in family happiness and family health were greater in the intervention group than in the control group. The savoring intervention had the most improved outcomes among the five themes. We concluded that this large-scale brief cRCT developed and conducted in real world settings provided evidence for the feasibility and effectiveness of a community-based family intervention. This study was registered under ClinicalTrials.gov (NCT01796275). PMID- 27199865 TI - Allocation of Study Time in Chinese Junior School Students: Habitual Responding, Item Difficulty, and Time Constraints. AB - The present study investigated factors influencing Chinese junior school students' study time allocation and the age difference in the effect of habitual responding. Participants were 240 junior school students (120 girls, 120 boys; aged 13-15 years) with half taking part in Experiment 1 and half in Experiment 2, and 240 young adults aged 18-23 years, (120 women and 120 men,) involved in Experiments 3a and 3b, all native Chinese speakers. In Experiments 1 and 3a, Chinese word pairs (e.g., moon-star) were presented on the screen with three items in one array. In each trial, the items were arranged from left to right, either easy, moderate, then difficult, or the reverse. Participants had either 5 s or no time limits to study the word pairs. In Experiments 2 and 3b, word pairs were ordered in a column with the easiest items either at the top or bottom position. Results showed interactions among item difficulty, item order, and time limitation in terms of effects on study time allocation of junior school students. Participants tended to learn the items in order (from left to right and from top to bottom), but the effect of item difficulty was greater than that of item order on item selection. Results indicated that agenda and habitual responding have a combined effect on study time allocation and that the contribution of agenda is greater than that of habitual responding. The effect of habitual responding on the self-paced study and recall performance of junior school students is greater than its effect on young adults, and the study time allocation of junior school students is more likely to be affected by external conditions. PMID- 27199866 TI - Openness to Experience as a Moderator of the Relationship between Intelligence and Creative Thinking: A Study of Chinese Children in Urban and Rural Areas. AB - Using testing and questionnaire methods, this study investigated the relationships among openness to experience, intelligence and creative thinking. This study focused on the moderating effects of openness to experience on the relationship between intelligence and creative thinking in a sample of 831 primary school students in China. The findings showed significant positive relationships among openness to experience, intelligence and creative thinking. In relation to the focus of this study, openness to experience moderated the relationship between intelligence and creative thinking. However, the correlation between openness to experience and creative thinking was stronger for urban children than for rural children, and the moderating effect existed only in urban settings. PMID- 27199868 TI - A Perceptual Motor Intervention Improves Play Behavior in Children with Moderate to Severe Cerebral Palsy. AB - For children with moderate or severe cerebral palsy (CP), a foundational early goal is independent sitting. Sitting offers additional opportunities for object exploration, play and social engagement. The achievement of sitting coincides with important milestones in other developmental areas, such as social engagement with others, understanding of spatial relationships, and the use of both hands to explore objects. These milestones are essential skills necessary for play behavior. However, little is known about how sitting and play behavior might be affected by a physical therapy intervention in children with moderate or severe CP. Therefore, our overall purpose in this study was to determine if sitting skill could be advanced in children with moderate to severe CP using a perceptual motor intervention, and if play skills would change significantly as sitting advanced. Thirty children between the ages of 18 months and 6 years who were able to hold prop sitting for at least 10 s were recruited for this study. Outcome measures were the sitting subsection of the Gross Motor Function Measure (GMFM), and the Play Assessment of Children with Motor Impairment play assessment scale, which is a modified version of the Play in Early Childhood Evaluation System. Significant improvements in GMFM sitting scores (p < 0.001) and marginally significant improvement in play assessment scores (p = 0.067) were found from pre to post-intervention. Sitting change explained a significant portion of the variance in play change for children over the age of 3 years, who were more severely affected by CP. The results of this study indicate that advances in sitting skill may be a factor in supporting improvements in functional play, along with age and severity of physical impairment. PMID- 27199867 TI - Physical Activity, Sleep, and Nutrition Do Not Predict Cognitive Performance in Young and Middle-Aged Adults. AB - Biological lifestyle factors (BLFs) such as physical activity, sleep, and nutrition play a role in cognitive functioning. Research concerning the relation between BLFs and cognitive performance is scarce however, especially in young and middle-aged adults. Research has not yet focused on a multidisciplinary approach with respect to this relation in the abovementioned population, where lifestyle habits are more stable. The aim of this study was to examine the contribution of these BLFs to cognitive performance. Path analysis was conducted in an observational study in which 1131 adults were analyzed using a cross-validation approach. Participants provided information on physical activity, sedentary behavior, chronotype, sleep duration, sleep quality, and the consumption of breakfast, fish, and caffeine via a survey. Their cognitive performance was measured using objective digital cognitive tests. Exploration yielded a predictive cohesive model that fitted the data properly, chi(2) /df = 0.8, CFI = 1.00, RMSEA < 0.001, SRMR = 0.016. Validation of the developed model indicated that the model fitted the data satisfactorily, chi(2) /df = 2.75, CFI = 0.95, RMSEA < 0.056, SRMR = 0.035. None of the variables within the BLFs were predictive for any of the cognitive performance measures, except for sedentary behavior. Although sedentary behavior was positively predictive for processing speed its contribution was small and unclear. The results indicate that the variables within the BLFs do not predict cognitive performance in young and middle-aged adults. PMID- 27199869 TI - Obesity Discrimination in the Recruitment Process: "You're Not Hired!". AB - Previous literature reports that obese persons are discriminated in the workplace. Evidence suggests that obese people are perceived as having less leadership potential, and in comparison to normal weight peers, are expected to be less successful. This study examined whether obese people are discriminated against when applying for employment. Three hypotheses were offered in line with previous research: (1) obese people are less likely to be assessed positively on personnel suitability than normal weight people; (2) obese people in active employment are more likely to be discriminated against than people in non-active employment; and (3) obese women are more likely to be discriminated against than obese men. 181 Participants were sampled from sedentary, standing, manual and heavy manual occupations. Participants rated hypothetical candidates on their suitability for employment. Employees also completed measures of implicit and explicit attitudes toward obesity. MANOVA was conducted to examine if obese candidates were discriminated against during the recruitment procedure. Results demonstrated that participants rated obese candidates as less suitable compared with normal weight candidates and when the weight status of the candidate was not revealed for work across the four workplace groups. Participant gender and weight status also impacted perceptions of candidates' suitability for work and discrimination toward obese candidates was higher in participants from more physically demanding occupations. The study findings contribute to evidence that obese people are discriminated against in the hiring process and support calls for policy development. PMID- 27199870 TI - The Impact of Language Opacity and Proficiency on Reading Strategies in Bilinguals: An Eye Movement Study. AB - Reading strategies vary across languages according to orthographic depth - the complexity of the grapheme in relation to phoneme conversion rules - notably at the level of eye movement patterns. We recently demonstrated that a group of early bilinguals, who learned both languages equally under the age of seven, presented a first fixation location (FFL) closer to the beginning of words when reading in German as compared with French. Since German is known to be orthographically more transparent than French, this suggested that different strategies were being engaged depending on the orthographic depth of the used language. Opaque languages induce a global reading strategy, and transparent languages force a local/serial strategy. Thus, pseudo-words were processed using a local strategy in both languages, suggesting that the link between word forms and their lexical representation may also play a role in selecting a specific strategy. In order to test whether corresponding effects appear in late bilinguals with low proficiency in their second language (L2), we present a new study in which we recorded eye movements while two groups of late German-French and French-German bilinguals read aloud isolated French and German words and pseudo-words. Since, a transparent reading strategy is local and serial, with a high number of fixations per stimuli, and the level of the bilingual participants' L2 is low, the impact of language opacity should be observed in L1. We therefore predicted a global reading strategy if the bilinguals' L1 was French (FFL close to the middle of the stimuli with fewer fixations per stimuli) and a local and serial reading strategy if it was German. Thus, the L2 of each group, as well as pseudo-words, should also require a local and serial reading strategy. Our results confirmed these hypotheses, suggesting that global word processing is only achieved by bilinguals with an opaque L1 when reading in an opaque language; the low level in the L2 gives way to a local and serial reading strategy. These findings stress the fact that reading behavior is influenced not only by the linguistic mode but also by top-down factors, such as readers' proficiency. PMID- 27199871 TI - Prospective Associations between Emotion Dysregulation and Fear-Potentiated Startle: The Moderating Effect of Respiratory Sinus Arrhythmia. AB - BACKGROUND: Emotion dysregulation has been implicated in the negative outcomes following trauma exposure. A proposed biomarker of emotion dysregulation, respiratory sinus arrhythmia (RSA), has demonstrated associations with trauma related phenomena, such as the fear-potentiated startle (FPS) response. The current study aimed to examine the prospective association between emotion dysregulation and RSA and FPS several years following trauma exposure. METHODS: Participants were 131 women exposed to a campus mass shooting on February 14, 2008. Pre-shooting emotion dysregulation was assessed in 2006-2008. Startle response, measured by orbicularis oculi electromyography (EMG), and RSA were gathered during an FPS paradigm conducted from 2012 to 2015. RESULTS: No significant associations among emotion dysregulation, RSA, and FPS emerged among the full sample. However, emotion dysregulation predicted FPS during both acquisition (r = 0.40, p < 0.05) and extinction (r = 0.57, p < 0.01) among individuals with high resting RSA. CONCLUSIONS: Findings suggest that pre shooting emotion dysregulation is a potent predictor of FPS several years following potential trauma exposure, and this association varies by RSA level. RESULTS emphasize the importance of examining autonomic regulation in the association between emotion dysregulation and recovery from trauma exposure. PMID- 27199872 TI - Commentary: Heart rate variability and self-control-A meta-analysis. PMID- 27199873 TI - Does Feedback-Related Brain Response during Reinforcement Learning Predict Socio motivational (In-)dependence in Adolescence? AB - This multi-methodological study applied functional magnetic resonance imaging to investigate neural activation in a group of adolescent students (N = 88) during a probabilistic reinforcement learning task. We related patterns of emerging brain activity and individual learning rates to socio-motivational (in-)dependence manifested in four different motivation types (MTs): (1) peer-dependent MT, (2) teacher-dependent MT, (3) peer-and-teacher-dependent MT, (4) peer-and-teacher independent MT. A multinomial regression analysis revealed that the individual learning rate predicts students' membership to the independent MT, or the peer and-teacher-dependent MT. Additionally, the striatum, a brain region associated with behavioral adaptation and flexibility, showed increased learning-related activation in students with motivational independence. Moreover, the prefrontal cortex, which is involved in behavioral control, was more active in students of the peer-and-teacher-dependent MT. Overall, this study offers new insights into the interplay of motivation and learning with (1) a focus on inter-individual differences in the role of peers and teachers as source of students' individual motivation and (2) its potential neurobiological basis. PMID- 27199874 TI - The Central Governor Model of Exercise Regulation Teaches Us Precious Little about the Nature of Mental Fatigue and Self-Control Failure. AB - Self-control is considered broadly important for many domains of life. One of its unfortunate features, however, is that it tends to wane over time, with little agreement about why this is the case. Recently, there has been a push to address this problem by looking to the literature in exercise physiology, specifically the work on the central governor model of physical fatigue. Trying to explain how and why mental performance wanes over time, the central governor model suggests that exertion is throttled by some central nervous system mechanism that receives information about energetic bodily needs and motivational drives to regulate exertion and, ultimately, to prevent homeostatic breakdown, chiefly energy depletion. While we admire the spirit of integration and the attempt to shed light on an important topic in psychology, our concern is that the central governor model is very controversial in exercise physiology, with increasing calls to abandon it altogether, making it a poor fit for psychology. Our concerns are threefold. First, while we agree that preservation of bodily homeostasis makes for an elegant ultimate account, the fact that such important homeostatic concerns can be regularly overturned with even slight incentives (e.g., a smile) renders the ultimate account impotent and points to other ultimate functions for fatigue. Second, despite the central governor being thought to take as input information about the metabolic needs of the body, there is no credible evidence that mental effort actually consumes inordinate amounts of energy that are not already circulating in the brain. Third, recent modifications of the model make the central governor appear like an all-knowing homunculus and unfalsifiable in principle, thus contributing very little to our understanding of why people tend to disengage from effortful tasks over time. We note that the latest models in exercise physiology have actually borrowed concepts and models from psychology to understand physical performance. PMID- 27199876 TI - The Effect of Perceived Parent-Child Facial Resemblance on Parents' Trait Anxiety: The Moderating Effect of Parents' Gender. AB - Father-child facial resemblance is an important cue for men to evaluate paternity. Previous studies found that fathers' perceptions of low facial resemblance with offspring lead to low confidence of paternity. Fathers' uncertainty of paternity could cause psychological stress and anxiety, which, after a long time, may further turn into trait anxiety. Conversely, females can ensure a biological connection with offspring because of internal fertilization. The purpose of this study was thus to examine the role of parents' gender in the effect of parents' perceived facial resemblance with child on their trait anxiety. In this study, 151 parents (father or mother) from one-child families reported their facial resemblance with child and their trait anxiety. Results showed that (i) males tended to perceive higher facial similarity with child than did females and (ii) males' perceived facial resemblance with child significantly predicted trait anxiety, whereas females' perceived facial resemblance did not. These findings suggested that the uncertainty of paternity contributed to the trait anxiety of fathers, but not mothers. PMID- 27199875 TI - Additivity of Feature-Based and Symmetry-Based Grouping Effects in Multiple Object Tracking. AB - Multiple object tracking (MOT) is an attentional process wherein people track several moving targets among several distractors. Symmetry, an important indicator of regularity, is a general spatial pattern observed in natural and artificial scenes. According to the "laws of perceptual organization" proposed by Gestalt psychologists, regularity is a principle of perceptual grouping, such as similarity and closure. A great deal of research reported that feature-based similarity grouping (e.g., grouping based on color, size, or shape) among targets in MOT tasks can improve tracking performance. However, no additive feature-based grouping effects have been reported where the tracking objects had two or more features. "Additive effect" refers to a greater grouping effect produced by grouping based on multiple cues instead of one cue. Can spatial symmetry produce a similar grouping effect similar to that of feature similarity in MOT tasks? Are the grouping effects based on symmetry and feature similarity additive? This study includes four experiments to address these questions. The results of Experiments 1 and 2 demonstrated the automatic symmetry-based grouping effects. More importantly, an additive grouping effect of symmetry and feature similarity was observed in Experiments 3 and 4. Our findings indicate that symmetry can produce an enhanced grouping effect in MOT and facilitate the grouping effect based on color or shape similarity. The "where" and "what" pathways might have played an important role in the additive grouping effect. PMID- 27199878 TI - Editorial: Bridging Reading Aloud and Speech Production. PMID- 27199877 TI - Effects of Age and Initial Risk Perception on Balloon Analog Risk Task: The Mediating Role of Processing Speed and Need for Cognitive Closure. AB - According to the dual-process theoretical perspective adopted in the presented research, the efficiency of deliberative processes in decision making declines with age, but experiential processes are relatively well-preserved. The age related differences in deliberative and experiential processes in risky decision making were examined in this research by applying the Balloon Analog Risk Task (BART). We analyzed the influence of age on risk acceptance and decision-making performance in two age groups of female participants (younger adults, n = 81; older adults, n = 76), with additional experimental manipulation of initial risk perception. We predicted and confirmed that aging significantly worsens performance on the behavioral BART measures due to age-related decline in deliberative processes. Older participants were found to exhibit significantly higher risk aversion and lower BART performance, and the effect of age was mediated by cognitive (processing speed) and motivational (need for cognitive closure) mechanisms. Moreover, older adults adapt to the initial failure (vs. success) similarly, as younger adults due to preserved efficiency of experiential processes. These results suggest future directions for minimizing negative effects of aging in risky decision-making and indicate compensatory processes, which are preserved during aging. PMID- 27199879 TI - Hedonic Capacity in the Broader Autism Phenotype: Should Social Anhedonia Be Considered a Characteristic Feature? AB - Impairments in social motivational processes may partially explain the differences in social interaction seen among individuals with autism spectrum disorder (ASD). The social motivation hypothesis would predict an association between reduced hedonic capacity and ASD. However, to date, findings have been mixed regarding hedonic deficits among individuals with ASD; adults report lower levels of both social and physical pleasure whereas adolescents only report experiencing lower social pleasure. Moreover, very few studies examining the association between anhedonia and autistic traits have used measures of hedonic response or taken temporal aspects of pleasure into account. The present study examined associations between autistic traits and the experience of pleasure using a non-clinical sample of young adults to further clarify the nature of hedonic deficits in the broader autism phenotype (BAP). Results revealed that autistic traits were negatively associated with both the experience of social pleasure as well as general pleasure, although the association was stronger for social pleasure. Regression analyses revealed that reduced social pleasure was a better predictor of autistic traits than general pleasure. Together these findings suggest that reduced social hedonic capacity is associated with autistic traits in the general population and should be included in conceptualizations of the BAP. PMID- 27199880 TI - Introduction of the Utrecht Tasks for Attention in Toddlers Using Eye Tracking (UTATE): A Pilot Study. AB - Attention capacities underlie everyday functioning from an early age onwards. Little is known about attentional processes at toddler age. A feasible assessment of attention capacities at toddler age is needed to allow further study of attention development. In this study, a test battery is piloted that consists of four tasks which intend to measure the attention systems orienting, alerting, and executive attention: the Utrecht Tasks of Attention in Toddlers using Eye tracking [UTATE]. The UTATE assesses looking behavior that may reflect visual attention capacities, by using eye-tracking methods. This UTATE was studied in 16 Dutch 18-month-old toddlers. Results showed that the instrument is feasible and generates good quality data. A first indication of sufficient reliability was found for most of the variables. It is concluded that the UTATE can be used in further studies. Further evaluation of the reliability and validity of the instrument in larger samples is worthwhile. PMID- 27199881 TI - A Reverse Stroop Task with Mouse Tracking. AB - In a reverse Stroop task, observers respond to the meaning of a color word irrespective of the color in which the word is printed-for example, the word red may be printed in the congruent color (red), an incongruent color (e.g., blue), or a neutral color (e.g., white). Although reading of color words in this task is often thought to be neither facilitated by congruent print colors nor interfered with incongruent print colors, this interference has been detected by using a response method that does not give any bias in favor of processing of word meanings or processing of print colors. On the other hand, evidence for the presence of facilitation in this task has been scarce, even though this facilitation is theoretically possible. By modifying the task such that participants respond to a stimulus color word by pointing to a corresponding response word on a computer screen with a mouse, the present study investigated the possibility that not only interference but also facilitation would take place in a reverse Stroop task. Importantly, in this study, participants' responses were dynamically tracked by recording the entire trajectories of the mouse. Arguably, this method provided richer information about participants' performance than traditional measures such as reaction time and accuracy, allowing for more detailed (and thus potentially more sensitive) investigation of facilitation and interference in the reverse Stroop task. These trajectories showed that the mouse's approach toward correct response words was significantly delayed by incongruent print colors but not affected by congruent print colors, demonstrating that only interference, not facilitation, was present in the current task. Implications of these findings are discussed within a theoretical framework in which the strength of association between a task and its response method plays a critical role in determining how word meanings and print colors interact in reverse Stroop tasks. PMID- 27199882 TI - Role of Alpha-Band Oscillations in Spatial Updating across Whole Body Motion. AB - When moving around in the world, we have to keep track of important locations in our surroundings. In this process, called spatial updating, we must estimate our body motion and correct representations of memorized spatial locations in accordance with this motion. While the behavioral characteristics of spatial updating across whole body motion have been studied in detail, its neural implementation lacks detailed study. Here we use electroencephalography (EEG) to distinguish various spectral components of this process. Subjects gazed at a central body-fixed point in otherwise complete darkness, while a target was briefly flashed, either left or right from this point. Subjects had to remember the location of this target as either moving along with the body or remaining fixed in the world while being translated sideways on a passive motion platform. After the motion, subjects had to indicate the remembered target location in the instructed reference frame using a mouse response. While the body motion, as detected by the vestibular system, should not affect the representation of body fixed targets, it should interact with the representation of a world-centered target to update its location relative to the body. We show that the initial presentation of the visual target induced a reduction of alpha band power in contralateral parieto-occipital areas, which evolved to a sustained increase during the subsequent memory period. Motion of the body led to a reduction of alpha band power in central parietal areas extending to lateral parieto-temporal areas, irrespective of whether the targets had to be memorized relative to world or body. When updating a world-fixed target, its internal representation shifts hemispheres, only when subjects' behavioral responses suggested an update across the body midline. Our results suggest that parietal cortex is involved in both self-motion estimation and the selective application of this motion information to maintaining target locations as fixed in the world or fixed to the body. PMID- 27199884 TI - Effects of Primary Blast Overpressure on Retina and Optic Tract in Rats. AB - Blast has been the leading cause of injury, particularly traumatic brain injury and visual system injury, in combat operations in Iraq and Afghanistan. We determined the effect of shock tube-generated primary blast on retinal electrophysiology and on retinal and brain optic tract histopathology in a rat model. The amplitude of a- and b-waves on the electroretinogram (ERG) for both right and left eyes were measured prior to a battlefield simulation Friedlander type blast wave and on 1, 7, and 14 days thereafter. Histopathologic findings of the right and left retina and the right and left optic tracts (2.8 mm postoptic chiasm) were evaluated 14 days after the blast. For two experiments in which the right eye was oriented to the blast, the amplitude of ERG a- and b-waves at 7 days post blast on the right side but not on the left side was diminished compared to that of sham animals (P = 0.005-0.01) Histopathologic injury scores at 14 days post blast for the right retina but not the left retina were higher than for sham animals (P = 0.01), and histopathologic injury scores at 14 days for both optic tracts were markedly higher than for shams (P < 0.0001). Exposure of one eye to a blast wave, comparable to that causing human injury, produced injury to the retina as determined by ERG and histopathology, and to both postchiasmatic optic tracts as determined by histopathology. This model may be useful for analyzing the effect of therapeutic interventions on retinal damage due to primary blast waves. PMID- 27199886 TI - A 1-Diopter Vertical Prism Induces a Decrease of Head Rotation: A Pilot Investigation. AB - Clinical studies in non-specific chronic arthralgia and back pain seem to indicate an association between vertical heterophoria (VH - latent vertical retinal misalignment) and asymmetrical head rotation. Such clinical observations suggest a link between VH and head rotation, but this was never tested. The purpose of this study was to simulate a VH in healthy subjects and examine its influence on the amplitude of active head rotation during 3D motion capture in upright stance. Subjects were asked to rotate their head three times from the straight ahead position and then to the right, back to straight ahead, to the left, and back to the straight ahead again. Three randomized conditions were run: normal viewing, with a 1-diopter prism base down on the dominant eye, or the non dominant eye. The most important finding is that the experimental VH whichever the eye with the prism induces a significant decrease in the mean angle of head rotation compared to the normal viewing condition. This decrease was significant for rotation to the left. We suggest that the prism-induced VH modifies the reference posture and thereby affects head rotation; further studies are needed to confirm this effect and to extend to other types of dynamic activities. PMID- 27199885 TI - Neuroimaging Assessment of Cerebrovascular Reactivity in Concussion: Current Concepts, Methodological Considerations, and Review of the Literature. AB - Concussion is a form of traumatic brain injury (TBI) that presents with a wide spectrum of subjective symptoms and few objective clinical findings. Emerging research suggests that one of the processes that may contribute to concussion pathophysiology is dysregulation of cerebral blood flow (CBF) leading to a mismatch between CBF delivery and the metabolic needs of the injured brain. Cerebrovascular reactivity (CVR) is defined as the change in CBF in response to a measured vasoactive stimulus. Several magnetic resonance imaging (MRI) techniques can be used as a surrogate measure of CBF in clinical and laboratory studies. In order to provide an accurate assessment of CVR, these sequences must be combined with a reliable, reproducible vasoactive stimulus that can manipulate CBF. Although CVR imaging currently plays a crucial role in the diagnosis and management of many cerebrovascular diseases, only recently have studies begun to apply this assessment tool in patients with concussion. In order to evaluate the quality, reliability, and relevance of CVR studies in concussion, it is important that clinicians and researchers have a strong foundational understanding of the role of CBF regulation in health, concussion, and more severe forms of TBI, and an awareness of the advantages and limitations of currently available CVR measurement techniques. Accordingly, in this review, we (1) discuss the role of CVR in TBI and concussion, (2) examine methodological considerations for MRI based measurement of CVR, and (3) provide an overview of published CVR studies in concussion patients. PMID- 27199887 TI - A Case of Acute Motor Axonal Neuropathy Mimicking Brain Death and Review of the Literature. AB - We describe a case report of fulminant Guillain-Barre syndrome (GBS) mimicking brain death. A previously healthy 60-year-old male was admitted to the neurointensive care unit after developing rapidly progressive weakness and respiratory failure. On presentation, the patient was found to have absent brainstem and spinal cord reflexes resembling that of brain death. Acute motor axonal neuropathy, a subtype of GBS, was diagnosed by cerebrospinal fluid and nerve conduction velocity testing. An electroencephalogram showed that the patient had normal, appropriately reactive brain function. Transcranial Doppler (TCD) ultrasound showed appropriate blood flow to the brain. GBS rarely presents with weakness so severe as to mimic brain death. This article provides a review of similar literature. This case demonstrates the importance of performing a proper brain death examination, which includes evaluation for irreversible cerebral injury, exclusion of any confounding conditions, and performance of tests such as electroencephalography and TCDs when uncertainty exists about the reliability of the clinical exam. PMID- 27199888 TI - ACTH Prevents Deficits in Fear Extinction Associated with Early Life Seizures. AB - OBJECTIVE: Early life seizures (ELS) are often associated with cognitive and psychiatric comorbidities that are detrimental to quality of life. In a rat model of ELS, we explored long-term cognitive outcomes in adult rats. Using ACTH, an endogeneous HPA-axis hormone given to children with severe epilepsy, we sought to prevent cognitive deficits. Through comparisons with dexamethasone, we sought to dissociate the corticosteroid effects of ACTH from other potential mechanisms of action. RESULTS: Although rats with a history of ELS were able to acquire a conditioned fear learning paradigm and controls, these rats had significant deficits in their ability to extinguish fearful memories. ACTH treatment did not alter any seizure parameters but nevertheless was able to significantly improve this fear extinction, while dexamethasone treatment during the same period did not. This ACTH effect was specific for fear extinction deficits and not for spatial learning deficits in a water maze. Additionally, ACTH did not alter seizure latency or duration suggesting that cognitive and seizure outcomes may be dissociable. Expression levels of melanocortin receptors, which bind ACTH, were found to be significantly lower in animals that had experienced ELS than in control animals, potentially implicating central melanocortin receptor dysregulation in the effects of ELS, and suggesting a mechanism of action for ACTH. INTERPRETATION: Taken together, these data suggest that early treatment with ACTH can have significant long-term consequences for cognition in animals with a history of ELS independently of seizure cessation and may act in part through a CNS melanocortin receptor pathway. PMID- 27199889 TI - Transcranial Direct Current Stimulation for Treatment of Childhood Pharmacoresistant Lennox-Gastaut Syndrome: A Pilot Study. AB - BACKGROUND: Lennox-Gastaut syndrome (LGS) is a severe childhood epileptic syndrome with high pharmacoresistance. The treatment outcomes are still unsatisfied. Our previous study of cathodal transcranial direct current stimulation (tDCS) in children with focal epilepsy showed significant reduction in epileptiform discharges. We hypothesized that cathodal tDCS when applied over the primary motor cortex (M1) combined with pharmacologic treatment will be more effective for reducing seizure frequency in patients with LGS than pharmacologic treatment alone. MATERIALS AND METHODS: Study participants were randomized to receive either (1) pharmacologic treatment with five consecutive days of 2 mA cathodal tDCS over M1 for 20 min or (2) pharmacologic treatment plus sham tDCS. Measures of seizure frequency and epileptic discharges were performed before treatment and again immediately post-treatment and 1-, 2-, 3-, and 4-week follow up. RESULT: Twenty-two patients with LGS were enrolled. Participants assigned to the active tDCS condition reported significantly more pre- to post-treatment reductions in seizure frequency and epileptic discharges that were sustained for 3 weeks after treatment. CONCLUSION: Five consecutive days of cathodal tDCS over M1 combined with pharmacologic treatment appears to reduce seizure frequency and epileptic discharges. Further studies of the potential mechanisms of tDCS in the LGS are warranted. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02731300 (https://register.clinicaltrials.gov). PMID- 27199883 TI - Rodent Hypoxia-Ischemia Models for Cerebral Palsy Research: A Systematic Review. AB - Cerebral palsy (CP) is a complex multifactorial disorder, affecting approximately 2.5-3/1000 live term births, and up to 22/1000 prematurely born babies. CP results from injury to the developing brain incurred before, during, or after birth. The most common form of this condition, spastic CP, is primarily associated with injury to the cerebral cortex and subcortical white matter as well as the deep gray matter. The major etiological factors of spastic CP are hypoxia/ischemia (HI), occurring during the last third of pregnancy and around birth age. In addition, inflammation has been found to be an important factor contributing to brain injury, especially in term infants. Other factors, including genetics, are gaining importance. The classic Rice-Vannucci HI model (in which 7-day-old rat pups undergo unilateral ligation of the common carotid artery followed by exposure to 8% oxygen hypoxic air) is a model of neonatal stroke that has greatly contributed to CP research. In this model, brain damage resembles that observed in severe CP cases. This model, and its numerous adaptations, allows one to finely tune the injury parameters to mimic, and therefore study, many of the pathophysiological processes and conditions observed in human patients. Investigators can recreate the HI and inflammation, which cause brain damage and subsequent motor and cognitive deficits. This model further enables the examination of potential approaches to achieve neural repair and regeneration. In the present review, we compare and discuss the advantages, limitations, and the translational value for CP research of HI models of perinatal brain injury. PMID- 27199890 TI - Stroke-Like Presentation Following Febrile Seizure in a Patient with 1q43q44 Deletion Syndrome. AB - Hemiconvulsion-hemiplegia-epilepsy syndrome (HHE) is a rare outcome of prolonged hemiconvulsion that is followed by diffuse unilateral hemispheric edema, hemiplegia, and ultimately hemiatrophy of the affected hemisphere and epilepsy. Here, we describe the case of a 3-year-old male with a 1;3 translocation leading to a terminal 1q43q44 deletion and a terminal 3p26.1p26.3 duplication that developed HHE after a prolonged febrile seizure and discuss the pathogenesis of HHE in the context of the patient's complex genetic background. PMID- 27199892 TI - Primary Hypothyroidism with Markedly High Prolactin. AB - Secondary pituitary enlargement due to primary hypothyroidism is not a common manifestation. The loss of thyroxin feedback inhibition in primary hypothyroidism causes overproduction of thyrotropin-releasing-hormone (TRH), which results in secondary pituitary enlargement. TRH has a weak stimulatory effect on the lactotroph cells of the pituitary, so a mild to moderate increase in prolactin (PRL) levels is expected. We report the case of a 67-year-old female who presented with a large pituitary mass and a very high level of TSH in association with a significant rise in PRL level. In this case, diagnosing a sellar mass was challenging; it was difficult to distinguish between pituitary prolactinoma and primary hypothyroidism with secondary pituitary hyperplasia. Thyroid hormone replacement proved that this patient's hyperprolactinemia was due to hyperplasia of the pituitary gland. As such, making the correct diagnosis and initiating thyroid hormone therapy can prevent unnecessary treatment with dopamine agonists. PMID- 27199891 TI - Bone Fragility in Turner Syndrome: Mechanisms and Prevention Strategies. AB - Bone fragility is recognized as one of the major comorbidities in Turner syndrome (TS). The mechanisms underlying bone impairment in affected patients are not clearly elucidated, but estrogen deficiency and X-chromosomal abnormalities represent important factors. Moreover, although many girls with TS undergo recombinant growth hormone therapy to treat short stature, the efficacy of this treatment on bone mineral density is controversial. The present review will focus on bone fragility in subjects with TS, providing an overview on the pathogenic mechanisms and some prevention strategies. PMID- 27199893 TI - RFRP Neurons - The Doorway to Understanding Seasonal Reproduction in Mammals. AB - Seasonal control of reproduction is critical for the perpetuation of species living in temperate zones that display major changes in climatic environment and availability of food resources. In mammals, seasonal cues are mainly provided by the annual change in the 24-h light/dark ratio (i.e., photoperiod), which is translated into the nocturnal production of the pineal hormone melatonin. The annual rhythm in this melatonin signal acts as a synchronizer ensuring that breeding occurs when environmental conditions favor survival of the offspring. Although specific mechanisms might vary among seasonal species, the hypothalamic RF (Arg-Phe) amide-related peptides (RFRP-1 and -3) are believed to play a critical role in the central control of seasonal reproduction and in all seasonal species investigated, the RFRP system is persistently inhibited in short photoperiod. Central chronic administration of RFRP-3 in short day-adapted male Syrian hamsters fully reactivates the reproductive axis despite photoinhibitory conditions, which highlights the importance of the seasonal changes in RFRP expression for proper regulation of the reproductive axis. The acute effects of RFRP peptides, however, depend on species and photoperiod, and recent studies point toward a different role of RFRP in regulating female reproductive activity. In this review, we summarize the recent advances made to understand the role and underlying mechanisms of RFRP in the seasonal control of reproduction, primarily focusing on mammalian species. PMID- 27199894 TI - Circadian Clocks, Stress, and Immunity. AB - In mammals, molecular circadian clocks are present in most cells of the body, and this circadian network plays an important role in synchronizing physiological processes and behaviors to the appropriate time of day. The hypothalamic pituitary-adrenal endocrine axis regulates the response to acute and chronic stress, acting through its final effectors - glucocorticoids - released from the adrenal cortex. Glucocorticoid secretion, characterized by its circadian rhythm, has an important role in synchronizing peripheral clocks and rhythms downstream of the master circadian pacemaker in the suprachiasmatic nucleus. Finally, glucocorticoids are powerfully anti-inflammatory, and recent work has implicated the circadian clock in various aspects and cells of the immune system, suggesting a tight interplay of stress and circadian systems in the regulation of immunity. This mini-review summarizes our current understanding of the role of the circadian clock network in both the HPA axis and the immune system, and discusses their interactions. PMID- 27199896 TI - Improving Control of Tuberculosis in Low-Burden Countries: Insights from Mathematical Modeling. AB - Tuberculosis control and elimination remains a challenge for public health even in low-burden countries. New technology and novel approaches to case-finding, diagnosis, and treatment are causes for optimism but they need to be used cost effectively. This in turn requires improved understanding of the epidemiology of TB and analysis of the effectiveness and cost-effectiveness of different interventions. We describe the contribution that mathematical modeling can make to understanding epidemiology and control of TB in different groups, guiding improved approaches to public health interventions. We emphasize that modeling is not a substitute for collecting data but rather is complementary to empirical research, helping determine what are the key questions to address to maximize the public-health impact of research, helping to plan studies, and making maximal use of available data, particularly from surveillance, and observational studies. We provide examples of how modeling and related empirical research inform policy and discuss how a combination of these approaches can be used to address current questions of key importance, including use of whole-genome sequencing, screening and treatment for latent infection, and combating drug resistance. PMID- 27199897 TI - Effects Due to Rhizospheric Soil Application of an Antagonistic Bacterial Endophyte on Native Bacterial Community and Its Survival in Soil: A Case Study with Pseudomonas aeruginosa from Banana. AB - Effective translation of research findings from laboratory to agricultural fields is essential for the success of biocontrol or growth promotion trials employing beneficial microorganisms. The rhizosphere is to be viewed holistically as a dynamic ecological niche comprising of diverse microorganisms including competitors and noxious antagonists to the bio-inoculant. This study was undertaken to assess the effects due to the soil application of an endophytic bacterium with multiple pathogen antagonistic potential on native bacterial community and its sustenance in agricultural soil. Pseudomonas aeruginosa was employed as a model system considering its frequent isolation as an endophyte, wide antagonistic effects reported against different phytopathogens and soil pests, and that the species is a known human pathogen which makes its usage in agriculture precarious. Employing the strain 'GNS.13.2a' from banana, its survival in field soil and the effects upon soil inoculation were investigated by monitoring total culturable bacterial fraction as the representative indicator of soil microbial community. Serial dilution plating of uninoculated control versus P. aeruginosa inoculated soil from banana rhizosphere indicated a significant reduction in native bacterial cfu soon after inoculation compared with control soil as assessed on cetrimide- nalidixic acid selective medium against nutrient agar. Sampling on day-4 showed a significant reduction in P. aeruginosa cfu in inoculated soil and a continuous dip thereafter registering >99% reduction within 1 week while the native bacterial population resurged with cfu restoration on par with control. This was validated in contained trials with banana plants. Conversely, P. aeruginosa showed static cfu or proliferation in axenic-soil. Lateral introduction of soil microbiome in P. aeruginosa established soil under axenic conditions or its co-incubation with soil microbiota in suspension indicated significant adverse effects by native microbial community. Direct agar plate challenge assays with individual environmental bacterial isolates displayed varying interactive or antagonistic effects. In effect, the application of P. aeruginosa in rhizospheric soil did not serve any net benefit in terms of sustained survival. Conversely, it caused a disturbance to the native soil bacterial community. The findings highlight the need for monitoring the bio inoculant(s) in field-soil and assessing the interactive effects with native microbial community before commercial recommendation. varying interactive or antagonistic effects. In effect, the application of P. aeruginosa in rhizospheric soil did not serve any net benefit in terms of sustained survival. Conversely, it caused a disturbance to the native soil bacterial community. The findings highlight the need for monitoring the bio-inoculant(s) in field-soil and assessing the interactive effects with native microbial community before commercial recommendation. PMID- 27199895 TI - The Role of Melatonin as a Hormone and an Antioxidant in the Control of Fish Reproduction. AB - Reproduction in most fish is seasonal or periodic, and the spawning occurs in an appropriate season to ensure maximum survival of the offspring. The sequence of reproductive events in an annual cycle is largely under the control of a species specific endogenous timing system, which essentially relies on a well-equipped physiological response mechanism to changing environmental cues. The duration of solar light or photoperiod is one of the most predictable environmental signals used by a large number of animals including fish to coordinate their seasonal breeding. In vertebrates, the pineal gland is the major photoneuroendocrine part of the brain that rhythmically synthesizes and releases melatonin (N-acetyl-5 methoxytryptamine) into the circulation in synchronization with the environmental light-dark cycle. Past few decades witnessed an enormous progress in understanding the mechanisms by which melatonin regulates seasonal reproduction in fish and in other vertebrates. Most studies emphasized hormonal actions of melatonin through its high-affinity, pertussis toxin-sensitive G-protein (guanine nucleotide-binding protein)-coupled receptors on the hypothalamus-pituitary-gonad (HPG) axis of fish. However, the discovery that melatonin due to its lipophilic nature can easily cross the plasma membrane of all cells and may act as a potent scavenger of free radicals and stimulant of different antioxidants added a new dimension to the idea explaining mechanisms of melatonin actions in the regulation of ovarian functions. The basic concept on the actions of melatonin as an antioxidant emerged from mammalian studies. Recently, however, some new studies clearly suggested that melatonin, apart from playing the role of a hormone, may also be associated with the reduction in oxidative stress to augment ovarian functions during spawning. This review thus aims to bring together the current knowledge on the role of melatonin as a hormone as well as an antioxidant in the control of fish reproduction and shape the current working hypotheses supported by recent findings obtained in carp or based on knowledge gathered in mammalian and avian species. In essence, this review highlights potential actions of melatonin as a hormone in determining temporal pattern of spawning and as an antioxidant in regulating oocyte maturation at the downstream of HPG axis in fish. PMID- 27199899 TI - A Novel Extracellular Gut Symbiont in the Marine Worm Priapulus caudatus (Priapulida) Reveals an Alphaproteobacterial Symbiont Clade of the Ecdysozoa. AB - Priapulus caudatus (phylum Priapulida) is a benthic marine predatory worm with a cosmopolitan distribution. In its digestive tract we detected symbiotic bacteria that were consistently present in specimens collected over 8 years from three sites at the Swedish west coast. Based on their 16S rRNA gene sequence, these symbionts comprise a novel genus of the order Rickettsiales (Alphaproteobacteria). Electron microscopy and fluorescence in situ hybridization (FISH) identified them as extracellular, elongate bacteria closely associated with the microvilli, for which we propose the name "Candidatus Tenuibacter priapulorum". Within Rickettsiales, they form a phylogenetically well-defined, family-level clade with uncultured symbionts of marine, terrestrial, and freshwater arthropods. Cand. Tenuibacter priapulorum expands the host range of this candidate family from Arthropoda to the entire Ecdysozoa, which may indicate an evolutionary adaptation of this bacterial group to the microvilli-lined guts of the Ecdysozoa. PMID- 27199898 TI - Method for Indirect Quantification of CH4 Production via H2O Production Using Hydrogenotrophic Methanogens. AB - Hydrogenotrophic methanogens are an intriguing group of microorganisms from the domain Archaea. Methanogens exhibit extraordinary ecological, biochemical, and physiological characteristics and possess a huge biotechnological potential. Yet, the only possibility to assess the methane (CH4) production potential of hydrogenotrophic methanogens is to apply gas chromatographic quantification of CH4. In order to be able to effectively screen pure cultures of hydrogenotrophic methanogens regarding their CH4 production potential we developed a novel method for indirect quantification of the volumetric CH4 production rate by measuring the volumetric water production rate. This method was established in serum bottles for cultivation of methanogens in closed batch cultivation mode. Water production was estimated by determining the difference in mass increase in a quasi-isobaric setting. This novel CH4 quantification method is an accurate and precise analytical technique, which can be used to rapidly screen pure cultures of methanogens regarding their volumetric CH4 evolution rate. It is a cost effective alternative determining CH4 production of methanogens over CH4 quantification by using gas chromatography, especially if applied as a high throughput quantification method. Eventually, the method can be universally applied for quantification of CH4 production from psychrophilic, thermophilic and hyperthermophilic hydrogenotrophic methanogens. PMID- 27199900 TI - A Novel MSCRAMM Subfamily in Coagulase Negative Staphylococcal Species. AB - Coagulase negative staphylococci (CoNS) are important opportunistic pathogens. Staphylococcus epidermidis, a coagulase negative staphylococcus, is the third leading cause of nosocomial infections in the US. Surface proteins like Microbial Surface Components Recognizing Adhesive Matrix Molecules (MSCRAMMs) are major virulence factors of pathogenic gram positive bacteria. Here, we identified a new chimeric protein in S. epidermidis, that we call SesJ. SesJ represents a prototype of a new subfamily of MSCRAMMs. Structural predictions show that SesJ has structural features characteristic of a MSCRAMM along with a N-terminal repeat region and an aspartic acid containing C-terminal repeat region, features that have not been previously observed in staphylococcal MSCRAMMs but have been found in other surface proteins from gram positive bacteria. We identified and analyzed structural homologs of SesJ in three other CoNS. These homologs of SesJ have an identical structural organization but varying sequence identities within the domains. Using flow cytometry, we also show that SesJ is expressed constitutively on the surface of a representative S. epidermidis strain, from early exponential to stationary growth phase. Thus, SesJ is positioned to interact with protein targets in the environment and plays a role in S. epidermidis virulence. PMID- 27199902 TI - Spatial and Temporal Profiling of Griseofulvin Production in Xylaria cubensis Using Mass Spectrometry Mapping. AB - A large portion of natural products research revolves around the discovery of new, bioactive chemical entities; however, studies to probe the biological purpose of such secondary metabolites for the host organism are often limited. Mass spectrometry mapping of secondary metabolite biosynthesis in situ can be used to probe a series of ecological questions about fungi that may be lost through traditional natural products chemistry extraction protocols. A griseofulvin-producing fungal culture of the Xylariaceae family, isolated as an endophyte of the tree Asimina triloba, was analyzed through a series of spatial and temporal mapping experiments. This fungus produced unique fungal characteristics, such as guttates and stroma, both of which were explored spatially. The distribution of griseofulvin on this culture in isolation was compared to its dispersal when grown in co-culture with a competing Penicillium species via a droplet-based surface sampling system. The fungistatic properties of griseofulvin were visualized, including the consequences for biosynthesis of polyhydroxyanthraquinones in a rival culture. PMID- 27199901 TI - Comparative Genetic Analyses of Human Rhinovirus C (HRV-C) Complete Genome from Malaysia. AB - Human rhinovirus-C (HRV-C) has been implicated in more severe illnesses than HRV A and HRV-B, however, the limited number of HRV-C complete genomes (complete 5' and 3' non-coding region and open reading frame sequences) has hindered the in depth genetic study of this virus. This study aimed to sequence seven complete HRV-C genomes from Malaysia and compare their genetic characteristics with the 18 published HRV-Cs. Seven Malaysian HRV-C complete genomes were obtained with newly redesigned primers. The seven genomes were classified as HRV-C6, C12, C22, C23, C26, C42, and pat16 based on the VP4/VP2 and VP1 pairwise distance threshold classification. Five of the seven Malaysian isolates, namely, 3430-MY-10/C22, 8713-MY-10/C23, 8097-MY-11/C26, 1570-MY-10/C42, and 7383-MY-10/pat16 are the first newly sequenced complete HRV-C genomes. All seven Malaysian isolates genomes displayed nucleotide similarity of 63-81% among themselves and 63-96% with other HRV-Cs. Malaysian HRV-Cs had similar putative immunogenic sites, putative receptor utilization and potential antiviral sites as other HRV-Cs. The genomic features of Malaysian isolates were similar to those of other HRV-Cs. Negative selections were frequently detected in HRV-Cs complete coding sequences indicating that these sequences were under functional constraint. The present study showed that HRV-Cs from Malaysia have diverse genetic sequences but share conserved genomic features with other HRV-Cs. This genetic information could provide further aid in the understanding of HRV-C infection. PMID- 27199903 TI - A Review on the Assessment of Stress Conditions for Simultaneous Production of Microalgal Lipids and Carotenoids. AB - Microalgal species are potential resource of both biofuels and high-value metabolites, and their production is growth dependent. Growth parameters can be screened for the selection of novel microalgal species that produce molecules of interest. In this context our review confirms that, autotrophic and heterotrophic organisms have demonstrated a dual potential, namely the ability to produce lipids as well as value-added products (particularly carotenoids) under influence of various physico-chemical stresses on microalgae. Some species of microalgae can synthesize, besides some pigments, very-long-chain polyunsaturated fatty acids (VL-PUFA,>20C) such as docosahexaenoic acid and eicosapentaenoic acid, those have significant applications in food and health. Producing value-added by products in addition to biofuels, fatty acid methyl esters (FAME), and lipids has the potential to improve microalgae-based biorefineries by employing either the autotrophic or the heterotrophic mode, which could be an offshoot of biotechnology. The review considers the potential of microalgae to produce a range of products and indicates future directions for developing suitable criteria for choosing novel isolates through bioprospecting large gene pool of microalga obtained from various habitats and climatic conditions. PMID- 27199905 TI - Isolation and Characterization of the First Xylanolytic Hyperthermophilic Euryarchaeon Thermococcus sp. Strain 2319x1 and Its Unusual Multidomain Glycosidase. AB - Enzymes from (hyper)thermophiles "Thermozymes" offer a great potential for biotechnological applications. Thermophilic adaptation does not only provide stability toward high temperature but is also often accompanied by a higher resistance to other harsh physicochemical conditions, which are also frequently employed in industrial processes, such as the presence of, e.g., denaturing agents as well as low or high pH of the medium. In order to find new thermostable, xylan degrading hydrolases with potential for biotechnological application we used an in situ enrichment strategy incubating Hungate tubes with xylan as the energy substrate in a hot vent located in the tidal zone of Kunashir Island (Kuril archipelago). Using this approach a hyperthermophilic euryarchaeon, designated Thermococcus sp. strain 2319x1, growing on xylan as sole energy and carbon source was isolated. The organism grows optimally at 85 degrees C and pH 7.0 on a variety of natural polysaccharides including xylan, carboxymethyl cellulose (CMC), amorphous cellulose (AMC), xyloglucan, and chitin. The protein fraction extracted from the cells surface with Tween 80 exhibited endoxylanase, endoglucanase and xyloglucanase activities. The genome of Thermococcus sp. strain 2319x1 was sequenced and assembled into one circular chromosome. Within the newly sequenced genome, a gene, encoding a novel type of glycosidase (143 kDa) with a unique five-domain structure, was identified. It consists of three glycoside hydrolase (GH) domains and two carbohydrate-binding modules (CBM) with the domain order GH5-12-12-CBM2-2 (N- to C-terminal direction). The full length protein, as well as truncated versions, were heterologously expressed in Escherichia coli and their activity was analyzed. The full length multidomain glycosidase (MDG) was able to hydrolyze various polysaccharides, with the highest activity for barley beta-glucan (beta- 1,3/1,4-glucoside), followed by that for CMC (beta-1,4 glucoside), cellooligosaccharides and galactomannan. The results reported here indicate that the modular MDG structure with multiple glycosidase and carbohydrate-binding domains not only extends the substrate spectrum, but also seems to allow the degradation of partially soluble and insoluble polymers in a processive manner. This report highlights the great potential in a multi-pronged approach consisting of a combined in situ enrichment, (comparative) genomics, and biochemistry strategy for the screening for novel enzymes of biotechnological relevance. PMID- 27199904 TI - Biologically Based Methods for Control of Fumonisin-Producing Fusarium Species and Reduction of the Fumonisins. AB - Infection by the fumonisin-producing Fusarium spp. and subsequent fumonisin contamination of maize adversely affect international trade and economy with deleterious effects on human and animal health. In developed countries high standards of the major food suppliers and retailers are upheld and regulatory controls deter the importation and local marketing of fumonisin-contaminated food products. In developing countries regulatory measures are either lacking or poorly enforced, due to food insecurity, resulting in an increased mycotoxin exposure. The lack and poor accessibility of effective and environmentally safe control methods have led to an increased interest in practical and biological alternatives to reduce fumonisin intake. These include the application of natural resources, including plants, microbial cultures, genetic material thereof, or clay minerals pre- and post-harvest. Pre-harvest approaches include breeding for resistant maize cultivars, introduction of biocontrol microorganisms, application of phenolic plant extracts, and expression of antifungal proteins and fumonisin degrading enzymes in transgenic maize cultivars. Post-harvest approaches include the removal of fumonisins by natural clay adsorbents and enzymatic degradation of fumonisins through decarboxylation and deamination by recombinant carboxylesterase and aminotransferase enzymes. Although, the knowledge base on biological control methods has expanded, only a limited number of authorized decontamination products and methods are commercially available. As many studies detailed the use of natural compounds in vitro, concepts in reducing fumonisin contamination should be developed further for application in planta and in the field pre-harvest, post-harvest, and during storage and food-processing. In developed countries an integrated approach, involving good agricultural management practices, hazard analysis and critical control point (HACCP) production, and storage management, together with selected biologically based treatments, mild chemical and physical treatments could reduce fumonisin contamination effectively. In rural subsistence farming communities, simple, practical, and culturally acceptable hand-sorting, maize kernel washing, and dehulling intervention methods proved to be effective as a last line of defense for reducing fumonisin exposure. Biologically based methods for control of fumonisin-producing Fusarium spp. and decontamination of the fumonisins could have potential commercial application, while simple and practical intervention strategies could also impact positively on food safety and security, especially in rural populations reliant on maize as a dietary staple. PMID- 27199906 TI - The Vitamin B1 and B12 Required by the Marine Dinoflagellate Lingulodinium polyedrum Can be Provided by its Associated Bacterial Community in Culture. AB - In this study we established the B1 and B12 vitamin requirement of the dinoflagellate Lingulodinium polyedrum and the vitamin supply by its associated bacterial community. In previous field studies the B1 and B12 demand of this species was suggested but not experimentally verified. When the axenic vitamin un supplemented culture (B-ns) of L. polyedrum was inoculated with a coastal bacterial community, the dinoflagellate's vitamin growth limitation was overcome, reaching the same growth rates as the culture growing in vitamin B1B7B12 supplemented (B-s) medium. Measured B12 concentrations in the B-s and B-ns cultures were both higher than typical coastal concentrations and B12 in the B-s culture was higher than in the B-ns culture. In both B-s and B-ns cultures, the probability of dinoflagellate cells having bacteria attached to the cell surface was similar and in both cultures an average of six bacteria were attached to each dinoflagellate cell. In the B-ns culture the free bacterial community showed significantly higher cell abundance suggesting that unattached bacteria supplied the vitamins. The fluorescence in situ hybridization (FISH) protocol allowed the quantification and identification of three bacterial groups in the same samples of the free and attached epibiotic bacteria for both treatments. The relative composition of these groups was not significantly different and was dominated by Alphaproteobacteria (>89%). To complement the FISH counts, 16S rDNA sequencing targeting the V3-V4 regions was performed using Illumina-MiSeq technology. For both vitamin amendments, the dominant group found was Alphaproteobacteria similar to FISH, but the percentage of Alphaproteobacteria varied between 50 and 95%. Alphaproteobacteria were mainly represented by Marivita sp., a member of the Roseobacter clade, followed by the Gammaproteobacterium Marinobacter flavimaris. Our results show that L. polyedrum is a B1 and B12 auxotroph, and acquire both vitamins from the associated bacterial community in sufficient quantity to sustain the maximum growth rate. PMID- 27199907 TI - Biodegradation of Mycotoxins: Tales from Known and Unexplored Worlds. AB - Exposure to mycotoxins, secondary metabolites produced by fungi, may infer serious risks for animal and human health and lead to economic losses. Several approaches to reduce these mycotoxins have been investigated such as chemical removal, physical binding, or microbial degradation. This review focuses on the microbial degradation or transformation of mycotoxins, with specific attention to the actual detoxification mechanisms of the mother compound. Furthermore, based on the similarities in chemical structure between groups of mycotoxins and environmentally recalcitrant compounds, known biodegradation pathways and degrading organisms which hold promise for the degradation of mycotoxins are presented. PMID- 27199909 TI - Selenite Reduction by Anaerobic Microbial Aggregates: Microbial Community Structure, and Proteins Associated to the Produced Selenium Spheres. AB - Certain types of anaerobic granular sludge, which consists of microbial aggregates, can reduce selenium oxyanions. To envisage strategies for removing those oxyanions from wastewater and recovering the produced elemental selenium (Se(0)), insights into the microbial community structure and synthesis of Se(0) within these microbial aggregates are required. High-throughput sequencing showed that Veillonellaceae (c.a. 20%) and Pseudomonadaceae (c.a.10%) were the most abundant microbial phylotypes in selenite reducing microbial aggregates. The majority of the Pseudomonadaceae sequences were affiliated to the genus Pseudomonas. A distinct outer layer (~200 MUm) of selenium deposits indicated that bioreduction occurred in the outer zone of the microbial aggregates. In that outer layer, SEM analysis showed abundant intracellular and extracellular Se(0) (nano)spheres, with some cells having high numbers of intracellular Se(0) spheres. Electron tomography showed that microbial cells can harbor a single large intracellular sphere that stretches the cell body. The Se(0) spheres produced by the microorganisms were capped with organic material. X-ray photoelectron spectroscopy (XPS) analysis of extracted Se(0) spheres, combined with a mathematical approach to analyzing XPS spectra from biological origin, indicated that proteins and lipids were components of the capping material associated to the Se(0) spheres. The most abundant proteins associated to the spheres were identified by proteomic analysis. Most of the proteins or peptide sequences capping the Se(0) spheres were identified as periplasmic outer membrane porins and as the cytoplasmic elongation factor Tu protein, suggesting an intracellular formation of the Se(0) spheres. In view of these and previous findings, a schematic model for the synthesis of Se(0) spheres by the microorganisms inhabiting the granular sludge is proposed. PMID- 27199911 TI - A Comprehensive Characterization of Simple Sequence Repeats in the Sequenced Trichoderma Genomes Provides Valuable Resources for Marker Development. AB - Members of genus Trichoderma are known worldwide for mycoparasitism. To gain a better insight into the organization and evolution of their genomes, we used an in silico approach to compare the occurrence, relative abundance and density of SSRs in Trichoderma atroviride, T. harzianum, T. reesei, and T. virens. Our analysis revealed that in all the four genome sequences studied, the occurrence, relative abundance, and density of microsatellites varied and was not influenced by genome sizes. The relative abundance and density of SSRs positively correlated with the G + C content of their genomes. The maximum frequency of SSRs was observed in the smallest genome of T. reesei whereas it was least in second smallest genome of T. atroviride. Among different classes of repeats, the tri nucleotide repeats were abundant in all the genomes and accounts for ~38%, whereas hexa-nuceotide repeats were the least (~10.2%). Further evaluation of the conservation of motifs in the transcript sequences shows a 49.5% conservation among all the motifs. In order to study polymorphism in Trichoderma isolates, 12 polymorphic SSR markers were developed. Of the 12 markers, 6 markers are from T. atroviride and remaining 6 belong to T. harzianum. SSR markers were found to be more polymorphic from T. atroviride with an average polymorphism information content value of 0.745 in comparison with T. harzianum (0.615). Twelve polymorphic markers obtained in this study clearly demonstrate the utility of newly developed SSR markers in establishing genetic relationships among different isolates of Trichoderma. PMID- 27199908 TI - Proteomic Stable Isotope Probing Reveals Biosynthesis Dynamics of Slow Growing Methane Based Microbial Communities. AB - Marine methane seep habitats represent an important control on the global flux of methane. Nucleotide-based meta-omics studies outline community-wide metabolic potential, but expression patterns of environmentally relevant proteins are poorly characterized. Proteomic stable isotope probing (proteomic SIP) provides additional information by characterizing phylogenetically specific, functionally relevant activity in mixed microbial communities, offering enhanced detection through system-wide product integration. Here we applied proteomic SIP to (15)[Formula: see text] and CH4 amended seep sediment microcosms in an attempt to track protein synthesis of slow-growing, low-energy microbial systems. Across all samples, 3495 unique proteins were identified, 11% of which were (15)N-labeled. Consistent with the dominant anaerobic oxidation of methane (AOM) activity commonly observed in anoxic seep sediments, proteins associated with sulfate reduction and reverse methanogenesis-including the ANME-2 associated methylenetetrahydromethanopterin reductase (Mer)-were all observed to be actively synthesized ((15)N-enriched). Conversely, proteins affiliated with putative aerobic sulfur-oxidizing epsilon- and gammaproteobacteria showed a marked decrease over time in our anoxic sediment incubations. The abundance and phylogenetic range of (15)N-enriched methyl-coenzyme M reductase (Mcr) orthologs, many of which exhibited novel post-translational modifications, suggests that seep sediments provide niches for multiple organisms performing analogous metabolisms. In addition, 26 proteins of unknown function were consistently detected and actively expressed under conditions supporting AOM, suggesting that they play important roles in methane seep ecosystems. Stable isotope probing in environmental proteomics experiments provides a mechanism to determine protein durability and evaluate lineage-specific responses in complex microbial communities placed under environmentally relevant conditions. Our work here demonstrates the active synthesis of a metabolically specific minority of enzymes, revealing the surprising longevity of most proteins over the course of an extended incubation experiment in an established, slow-growing, methane impacted environmental system. PMID- 27199910 TI - Genomic and Secondary Metabolite Analyses of Streptomyces sp. 2AW Provide Insight into the Evolution of the Cycloheximide Pathway. AB - The dearth of new antibiotics in the face of widespread antimicrobial resistance makes developing innovative strategies for discovering new antibiotics critical for the future management of infectious disease. Understanding the genetics and evolution of antibiotic producers will help guide the discovery and bioengineering of novel antibiotics. We discovered an isolate in Alaskan boreal forest soil that had broad antimicrobial activity. We elucidated the corresponding antimicrobial natural products and sequenced the genome of this isolate, designated Streptomyces sp. 2AW. This strain illustrates the chemical virtuosity typical of the Streptomyces genus, producing cycloheximide as well as two other biosynthetically unrelated antibiotics, neutramycin, and hygromycin A. Combining bioinformatic and chemical analyses, we identified the gene clusters responsible for antibiotic production. Interestingly, 2AW appears dissimilar from other cycloheximide producers in that the gene encoding the polyketide synthase resides on a separate part of the chromosome from the genes responsible for tailoring cycloheximide-specific modifications. This gene arrangement and our phylogenetic analyses of the gene products suggest that 2AW holds an evolutionarily ancestral lineage of the cycloheximide pathway. Our analyses support the hypothesis that the 2AW glutaramide gene cluster is basal to the lineage wherein cycloheximide production diverged from other glutarimide antibiotics. This study illustrates the power of combining modern biochemical and genomic analyses to gain insight into the evolution of antibiotic-producing microorganisms. PMID- 27199912 TI - Sequence-Based Characterization of Tn5801-Like Genomic Islands in Tetracycline Resistant Staphylococcus pseudintermedius and Other Gram-positive Bacteria from Humans and Animals. AB - Antibiotic resistance in pathogens is often associated with mobile genetic elements, such as genomic islands (GI) including integrative and conjugative elements (ICEs). These can transfer resistance genes within and between bacteria from humans and/or animals. The aim of this study was to investigate whether Tn5801-like GIs carrying the tetracycline resistance gene, tet(M), are common in Staphylococcus pseudintermedius from pets, and to do an overall sequences-based characterization of Tn5801-like GIs detected in Gram-positive bacteria from humans and animals. A total of 27 tetracycline-resistant S. pseudintermedius isolates from Danish pets (1998-2005) were screened for tet(M) by PCR. Selected isolates (13) were screened for GI- or ICE-specific genes (int Tn5801 or xis Tn916 ) and their tet(M) gene was sequenced (Sanger-method). Long-range PCR mappings and whole-genome-sequencing (Illumina) were performed for selected S. pseudintermedius-isolates (seven and three isolates, respectively) as well as for human S. aureus isolates (seven and one isolates, respectively) and one porcine Enterococcus faecium isolate known to carry Tn5801-like GIs. All 27 S. pseudintermedius were positive for tet(M). Out of 13 selected isolates, seven contained Tn5801-like GIs and six contained Tn916-like ICEs. Two different Tn5801 like GI types were detected among S. pseudintermedius (Tn5801 and GI6287) - both showed high similarity compared to GenBank sequences from human pathogens. Two distinct Tn5801-like GI types were detected among the porcine E. faecium and human S. aureus isolates (Tn6014 and GI6288). Tn5801-like GIs were detected in GenBank-sequences from Gram-positive bacteria of human, animal or food origin worldwide. Known Tn5801-like GIs were divided into seven types. The results showed that Tn5801-like GIs appear to be relatively common in tetracycline resistant S. pseudintermedius in Denmark. Almost identical Tn5801-like GIs were identified in different Gram-positive species of pet and human origin, suggesting that horizontal transfer of these elements has occurred between S. pseudintermedius from pets and human pathogens, including S. aureus. PMID- 27199913 TI - Functional Properties of Microorganisms in Fermented Foods. AB - Fermented foods have unique functional properties imparting some health benefits to consumers due to presence of functional microorganisms, which possess probiotics properties, antimicrobial, antioxidant, peptide production, etc. Health benefits of some global fermented foods are synthesis of nutrients, prevention of cardiovascular disease, prevention of cancer, gastrointestinal disorders, allergic reactions, diabetes, among others. The present paper is aimed to review the information on some functional properties of the microorganisms associated with fermented foods and beverages, and their health-promoting benefits to consumers. PMID- 27199914 TI - Metagenomics Reveals Pervasive Bacterial Populations and Reduced Community Diversity across the Alaska Tundra Ecosystem. AB - How soil microbial communities contrast with respect to taxonomic and functional composition within and between ecosystems remains an unresolved question that is central to predicting how global anthropogenic change will affect soil functioning and services. In particular, it remains unclear how small-scale observations of soil communities based on the typical volume sampled (1-2 g) are generalizable to ecosystem-scale responses and processes. This is especially relevant for remote, northern latitude soils, which are challenging to sample and are also thought to be more vulnerable to climate change compared to temperate soils. Here, we employed well-replicated shotgun metagenome and 16S rRNA gene amplicon sequencing to characterize community composition and metabolic potential in Alaskan tundra soils, combining our own datasets with those publically available from distant tundra and temperate grassland and agriculture habitats. We found that the abundance of many taxa and metabolic functions differed substantially between tundra soil metagenomes relative to those from temperate soils, and that a high degree of OTU-sharing exists between tundra locations. Tundra soils were an order of magnitude less complex than their temperate counterparts, allowing for near-complete coverage of microbial community richness (~92% breadth) by sequencing, and the recovery of 27 high-quality, almost complete (>80% completeness) population bins. These population bins, collectively, made up to ~10% of the metagenomic datasets, and represented diverse taxonomic groups and metabolic lifestyles tuned toward sulfur cycling, hydrogen metabolism, methanotrophy, and organic matter oxidation. Several population bins, including members of Acidobacteria, Actinobacteria, and Proteobacteria, were also present in geographically distant (~100-530 km apart) tundra habitats (full genome representation and up to 99.6% genome-derived average nucleotide identity). Collectively, our results revealed that Alaska tundra microbial communities are less diverse and more homogenous across spatial scales than previously anticipated, and provided DNA sequences of abundant populations and genes that would be relevant for future studies of the effects of environmental change on tundra ecosystems. PMID- 27199915 TI - Evolution of a Sigma Factor: An All-In-One of Gene Duplication, Horizontal Gene Transfer, Purifying Selection, and Promoter Differentiation. AB - Sigma factors are an essential part of bacterial gene regulation and have been extensively studied as far as their molecular mechanisms and protein structure are concerned. However, their molecular evolution, especially for the alternative sigma factors, is poorly understood. Here, we analyze the evolutionary forces that have shaped the rpoH sigma factors within the alphaproteobacteria. We found that an ancient duplication gave rise to two major groups of rpoH sigma factors and that after this event horizontal gene transfer (HGT) occurred in rpoH 1 group. We also noted that purifying selection has differentially affected distinct parts of the gene; singularly, the gene segment that encodes the region 4.2, which interacts with the -35 motif of the RpoH-dependent genes, has been under relaxed purifying selection. Furthermore, these two major groups are clearly differentiated from one another regarding their promoter selectivity, as rpoH 1 is under the transcriptional control of sigma(70) and sigma(32), whereas rpoH 2 is under the transcriptional control of sigma(24). Our results suggest a scenario in which HGT, gene loss, variable purifying selection and clear promoter specialization occurred after the ancestral duplication event. More generally, our study offers insights into the molecular evolution of alternative sigma factors and highlights the importance of analyzing not only the coding regions but also the promoter regions. PMID- 27199916 TI - Development of Ruminal and Fecal Microbiomes Are Affected by Weaning But Not Weaning Strategy in Dairy Calves. AB - The nature of weaning, considered the most stressful and significant transition experienced by dairy calves, influences the ability of a calf to adapt to the dramatic dietary shift, and thus, can influence the severity of production losses through the weaning transition. However, the effects of various feeding strategies on the development of rumen or fecal microbiota across weaning are yet to be examined. Here we characterized the pre- and post-weaning ruminal and fecal microbiomes of Holstein dairy calves exposed to two different weaning strategies, gradual (step-down) or abrupt. We describe the shifts toward a mature ruminant state, a transition which is hastened by the introduction of the solid feeds initiating ruminal fermentation. Additionally, we discuss the predicted functional roles of these communities, which also appear to represent that of the mature gastrointestinal system prior to weaning, suggesting functional maturity. This assumed state of readiness also appeared to negate the effects of weaning strategy on ruminal and fecal microbiomes and therefore, we conclude that the shift in gastrointestinal microbiota may not account for the declines in gain and intakes observed in calves during an abrupt weaning. PMID- 27199917 TI - Co-cultivation of Aspergillus nidulans Recombinant Strains Produces an Enzymatic Cocktail as Alternative to Alkaline Sugarcane Bagasse Pretreatment. AB - Plant materials represent a strategic energy source because they can give rise to sustainable biofuels through the fermentation of their carbohydrates. A clear example of a plant-derived biofuel resource is the sugar cane bagasse exhibiting 60-80% of fermentable sugars in its composition. However, the current methods of plant bioconversion employ severe and harmful chemical/physical pretreatments raising biofuel cost production and environmental degradation. Replacing these methods with co-cultivated enzymatic cocktails is an alternative. Here we propose a pretreatment for sugarcane bagasse using a multi-enzymatic cocktail from the co cultivation of four Aspergillus nidulans recombinant strains. The co-cultivation resulted in the simultaneous production of GH51 arabinofuranosidase (AbfA), GH11 endo-1,4-xylanase (XlnA), GH43 endo-1,5-arabinanase (AbnA) and GH12 xyloglucan specific endo-beta-1,4-glucanase (XegA). This core set of recombinant enzymes was more efficient than the alternative alkaline method in maintaining the cellulose integrity and exposing this cellulose to the following saccharification process. Thermogravimetric and differential thermal analysis revealed residual byproducts on the alkali pretreated biomass, which were not found in the enzymatic pretreatment. Therefore, the enzymatic pretreatment was residue-free and seemed to be more efficient than the applied alkaline method, which makes it suitable for bioethanol production. PMID- 27199918 TI - Effect of Galacto-Oligosaccharides: Maltodextrin Matrices on the Recovery of Lactobacillus plantarum after Spray-Drying. AB - In this work maltodextrins were added to commercial galacto-oligosaccharides (GOS) in a 1:1 ratio and their thermophysical characteristics were analyzed. GOS:MD solutions were then used as matrices during spray-drying of Lactobacillus plantarum CIDCA 83114. The obtained powders were equilibrated at different relative humidities (RH) and stored at 5 and 20 degrees C for 12 weeks, or at 30 degrees C for 6 weeks. The Tgs of GOS:MD matrices were about 20-30 degrees C higher than those of GOS at RH within 11 and 52%. A linear relation between the spin-spin relaxation time (T2) and T-Tg parameter was observed for GOS:MD matrices equilibrated at 11, 22, 33, and 44% RH at 5, 20, and 30 degrees C. Spray drying of L. plantarum CIDCA 83114 in GOS:MD matrices allowed the recovery of 93% microorganisms. In contrast, only 64% microorganisms were recovered when no GOS were included in the dehydration medium. Survival of L. plantarum CIDCA 83114 during storage showed the best performance for bacteria stored at 5 degrees C. In a further step, the slopes of the linear regressions provided information about the rate of microbial inactivation for each storage condition (k values). This information can be useful to calculate the shelf-life of spray-dried starters stored at different temperatures and RH. Using GOS:MD matrices as a dehydration medium enhanced the recovery of L. plantarum CIDCA 83114 after spray-drying. This strategy allowed for the first time the spray-drying stabilization of a potentially probiotic strain in the presence of GOS. PMID- 27199920 TI - Antibiotic Resistance Patterns of Pseudomonas spp. Isolated from the River Danube. AB - Spread and persistence of antibiotic resistance pose a severe threat to human health, yet there is still lack of knowledge about reservoirs of antibiotic resistant bacteria in the environment. We took the opportunity of the Joint Danube Survey 3 (JDS3), the world's biggest river research expedition of its kind in 2013, to analyse samples originating from different sampling points along the whole length of the river. Due to its high clinical relevance, we concentrated on the characterization of Pseudomonas spp. and evaluated the resistance profiles of Pseudomonas spp. which were isolated from eight sampling points. In total, 520 Pseudomonas isolates were found, 344 (66.0%) isolates were identified as Pseudomonas putida, and 141 (27.1%) as Pseudomonas fluorescens, all other Pseudomonas species were represented by less than five isolates, among those two P. aeruginosa isolates. Thirty seven percent (37%) of all isolated Pseudomonas species showed resistance to at least one out of 10 tested antibiotics. The most common resistance was against meropenem (30.4%/158 isolates) piperacillin/tazobactam (10.6%/55 isolates) and ceftazidime (4.2%/22 isolates). 16 isolates (3.1%/16 isolates) were multi-resistant. For each tested antibiotic at least one resistant isolate could be detected. Sampling points from the upper stretch of the River Danube showed more resistant isolates than downriver. Our results suggest that antibiotic resistance can be acquired by and persists even in Pseudomonas species that are normally not in direct contact with humans. A possible scenario is that these bacteria provide a reservoir of antibiotic resistance genes that can spread to related human pathogens by horizontal gene transfer. PMID- 27199921 TI - Characterization of the Deamination Coupled with Sliding along DNA of Anti-HIV Factor APOBEC3G on the Basis of the pH-Dependence of Deamination Revealed by Real Time NMR Monitoring. AB - Human APOBEC3G (A3G) is an antiviral factor that inactivates HIV. The C-terminal domain of A3G (A3G-CTD) deaminates cytosines into uracils within single-stranded DNA (ssDNA), which is reverse-transcribed from the viral RNA genome. The deaminase activity of A3G is highly sequence-specific; the third position (underlined) of a triplet cytosine (CCC) hotspot is converted into CCU. A3G deaminates a CCC that is located close to the 5' end of ssDNA more effectively than ones that are less close to the 5' end, so-called 3' -> 5' polarity. We had developed an NMR method that can be used to analyze the deamination reaction in real-time. Using this method, we previously showed that 3' -> 5' polarity can be explained rationally by A3G-CTD's nonspecific ssDNA-binding and sliding direction dependent deamination activities. We then demonstrated that the phosphate backbone is important for A3G-CTD to slide on the ssDNA and to exert the 3' -> 5' polarity, probably due to an electrostatic intermolecular interaction. In this study, we investigate the pH effects on the structure, deaminase activity, and 3' -> 5' polarity of A3G-CTD. Firstly, A3G-CTD was shown to retain the native structure in the pH range of 4.0-10.5 by CD spectroscopy. Next, deamination assaying involving real-time NMR spectroscopy for 10-mer ssDNA containing a single CCC revealed that A3G-CTD's deaminase activity decreases as the pH increases in the range of pH 6.5-12.7. This is explained by destabilization of the complex between A3G-CTD and ssDNA due to the weakened electrostatic interaction with the increase in pH. Finally, deamination assaying for 38-mer ssDNA having two CCC hotspots connected by a long poly-adenine linker showed that A3G-CTD retains the same pH deaminase activity preference toward each CCC as that toward the CCC of the 10-mer DNA. Importantly, the 3' -> 5' polarity turned out to increase as the pH decreases in the range of 6.5-8.0. This suggests that A3G CTD tends to continue sliding without abortion at lower pH, while A3G-CTD tends to dissociate from ssDNA during sliding at higher pH due to the weakened electrostatic interaction. PMID- 27199922 TI - Antimicrobial Susceptibility Profiles of Human Campylobacter jejuni Isolates and Association with Phylogenetic Lineages. AB - Campylobacter jejuni is a zoonotic pathogen and the most common bacterial cause of human gastroenteritis worldwide. With the increase of antibiotic resistance to fluoroquinolones and macrolides, the drugs of choice for treatment, C. jejuni was recently classified as a serious antimicrobial resistant threat. Here, we characterized 94 C. jejuni isolates collected from patients at four Michigan hospitals in 2011 and 2012 to determine the frequency of resistance and association with phylogenetic lineages. The prevalence of resistance to fluoroquinolones (19.1%) and macrolides (2.1%) in this subset of C. jejuni isolates from Michigan was similar to national reports. High frequencies of fluoroquinolone-resistant C. jejuni isolates, however, were recovered from patients with a history of foreign travel. A high proportion of these resistant isolates were classified as multilocus sequence type (ST)-464, a fluoroquinolone resistant lineage that recently emerged in Europe. A significantly higher prevalence of tetracycline-resistant C. jejuni was also found in Michigan and resistant isolates were more likely to represent ST-982, which has been previously recovered from ruminants and the environment in the U.S. Notably, patients with tetracycline-resistant C. jejuni infections were more likely to have contact with cattle. These outcomes prompt the need to monitor the dissemination and diversification of imported fluoroquinolone-resistant C. jejuni strains and to investigate the molecular epidemiology of C. jejuni recovered from cattle and farm environments to guide mitigation strategies. PMID- 27199923 TI - Bacterioplankton Biogeography of the Atlantic Ocean: A Case Study of the Distance Decay Relationship. AB - In order to determine the influence of geographical distance, depth, and Longhurstian province on bacterial community composition and compare it with the composition of photosynthetic micro-eukaryote communities, 382 samples from a depth-resolved latitudinal transect (51 degrees S-47 degrees N) from the epipelagic zone of the Atlantic ocean were analyzed by Illumina amplicon sequencing. In the upper 100 m of the ocean, community similarity decreased toward the equator for 6000 km, but subsequently increased again, reaching similarity values of 40-60% for samples that were separated by ~12,000 km, resulting in a U-shaped distance-decay curve. We conclude that adaptation to local conditions can override the linear distance-decay relationship in the upper epipelagial of the Atlantic Ocean which is apparently not restrained by barriers to dispersal, since the same taxa were shared between the most distant communities. The six Longhurstian provinces covered by the transect were comprised of distinct microbial communities; ~30% of variation in community composition could be explained by province. Bacterial communities belonging to the deeper layer of the epipelagic zone (140-200 m) lacked a distance-decay relationship altogether and showed little provincialism. Interestingly, those biogeographical patterns were consistently found for bacteria from three different size fractions of the plankton with different taxonomic composition, indicating conserved underlying mechanisms. Analysis of the chloroplast 16S rRNA gene sequences revealed that phytoplankton composition was strongly correlated with both free-living and particle associated bacterial community composition (R between 0.51 and 0.62, p < 0.002). The data show that biogeographical patterns commonly found in macroecology do not hold for marine bacterioplankton, most likely because dispersal and evolution occur at drastically different rates in bacteria. PMID- 27199919 TI - The Modulation of Apoptotic Pathways by Gammaherpesviruses. AB - Apoptosis or programmed cell death is a tightly regulated process fundamental for cellular development and elimination of damaged or infected cells during the maintenance of cellular homeostasis. It is also an important cellular defense mechanism against viral invasion. In many instances, abnormal regulation of apoptosis has been associated with a number of diseases, including cancer development. Following infection of host cells, persistent and oncogenic viruses such as the members of the Gammaherpesvirus family employ a number of different mechanisms to avoid the host cell's "burglar" alarm and to alter the extrinsic and intrinsic apoptotic pathways by either deregulating the expressions of cellular signaling genes or by encoding the viral homologs of cellular genes. In this review, we summarize the recent findings on how gammaherpesviruses inhibit cellular apoptosis via virus-encoded proteins by mediating modification of numerous signal transduction pathways. We also list the key viral anti-apoptotic proteins that could be exploited as effective targets for novel antiviral therapies in order to stimulate apoptosis in different types of cancer cells. PMID- 27199925 TI - Morphological Characteristics of Schistosoma mansoni PZQ-Resistant and Susceptible Strains Are Different in Presence of Praziquantel. AB - Schistosomiasis is one of the most common human parasitic diseases whose socioeconomic impact is only surpassed by malaria. Praziquantel (PZQ) is the only drug commercially available for the treatment of all schistosome species causing disease in humans. However, there has been stronger evidences of PZQ-resistance on Schistosoma mansoni and thus it is very important to study the phenotypic characteristics associated with it. The aim of this study was to evaluate morphological alterations in S. mansoni PZQ-resistant adult worms and eggs, by comparing a PZQ- resistant strain obtained under PZQ drug pressure with a PZQ susceptible strain. For this, scanning electronic microscopy was used to assess tegumental responsiveness of both strains under PZQ exposure, and optical microscopy allowed the monitoring of worms and eggs in the presence of the drug. Those assays showed that PZQ-susceptible worms exposed to the drug had more severe tegumental damages than the resistant one, which had only minor alterations. Moreover, contrary to what occurred in the susceptible strain, resistant worms were viable after PZQ exposure and gradually regaining full motility after removal of the drug. Eggs from resistant strain parasites are considerably smaller than those from susceptible strain. Our results suggest that there might be a difference in the tegument composition of the resistant strain and that worms are less responsive to PZQ. Changes observed in egg morphology might imply alterations in the biology of schistosomes associated to PZQ resistance, which could impact on transmission and pathology of the disease. Moreover, we propose a hypothetical scenario where there is a different egg tropism of the S. mansoni resistant strain. This study is the first comparing two strains that only differ in their resistance characteristics, which makes it a relevant step in the search for resistance determinants. PMID- 27199926 TI - Mycoplasma bovis: Mechanisms of Resistance and Trends in Antimicrobial Susceptibility. AB - Mycoplasma bovis is a cell-wall-less bacterium and belongs to the class Mollicutes. It is the most important etiological agent of bovine mycoplasmoses in North America and Europe, causing respiratory disease, mastitis, otitis media, arthritis, and reproductive disease. Clinical disease associated with M. bovis is often chronic, debilitating, and poorly responsive to antimicrobial therapy, resulting in significant economic loss, the full extent of which is difficult to estimate. Until M. bovis vaccines are universally available, sanitary control measures and antimicrobial treatment are the only approaches that can be used in attempts to control M. bovis infections. However, in vitro studies show that many of the current M. bovis isolates circulating in Europe have high minimum inhibitory concentrations (MIC) for many of the commercially available antimicrobials. In this review we summarize the current MIC trends indicating the development of antimicrobial resistance in M. bovis as well as the known molecular mechanisms by which resistance is acquired. PMID- 27199924 TI - Anti-biofilm Activity as a Health Issue. AB - The formation and persistence of surface-attached microbial communities, known as biofilms, are responsible for 75% of human microbial infections (National Institutes of Health). Biofilm lifestyle confers several advantages to the pathogens, notably during the colonization process of medical devices and/or patients' organs. In addition, sessile bacteria have a high tolerance to exogenous stress including anti-infectious agents. Biofilms are highly competitive communities and some microorganisms exhibit anti-biofilm capacities such as bacterial growth inhibition, exclusion or competition, which enable them to acquire advantages and become dominant. The deciphering and control of anti biofilm properties represent future challenges in human infection control. The aim of this review is to compare and discuss the mechanisms of natural bacterial anti-biofilm strategies/mechanisms recently identified in pathogenic, commensal and probiotic bacteria and the main synthetic strategies used in clinical practice, particularly for catheter-related infections. PMID- 27199927 TI - Comparison of Transcriptional Heterogeneity of Eight Genes between Batch Desulfovibrio vulgaris Biofilm and Planktonic Culture at a Single-Cell Level. AB - Sulfate-reducing bacteria (SRB) biofilm formed on metal surfaces can change the physicochemical properties of metals and cause metal corrosion. To enhance understanding of differential gene expression in Desulfovibrio vulgaris under planktonic and biofilm growth modes, a single-cell based RT-qPCR approach was applied to determine gene expression levels of 8 selected target genes in four sets of the 31 individual cells isolated from each growth condition (i.e., biofilm formed on a mild steel (SS) and planktonic cultures, exponential and stationary phases). The results showed obvious gene-expression heterogeneity for the target genes among D. vulgaris single cells of both biofilm and planktonic cultures. In addition, an increased gene-expression heterogeneity in the D. vulgaris biofilm when compared with the planktonic culture was also observed for seven out of eight selected genes at exponential phase, and six out of eight selected genes at stationary phase, respectively, which may be contributing to the increased complexity in terms of structures and morphology in the biofilm. Moreover, the results showed up-regulation of DVU0281 gene encoding exopolysaccharide biosynthesis protein, and down-regulation of genes involved in energy metabolism (i.e., DVU0434 and DVU0588), stress responses (i.e., DVU2410) and response regulator (i.e., DVU3062) in the D. vulgaris biofilm cells. Finally, the gene (DVU2571) involved in iron transportation was found down-regulated, and two genes (DVU1340 and DVU1397) involved in ferric uptake repressor and iron storage were up-regulated in D. vulgaris biofilm, suggesting their possible roles in maintaining normal metabolism of the D. vulgaris biofilm under environments of high concentration of iron. This study showed that the single-cell based analysis could be a useful approach in deciphering metabolism of microbial biofilms. PMID- 27199929 TI - The Small RNA DsrA Influences the Acid Tolerance Response and Virulence of Salmonella enterica Serovar Typhimurium. AB - The Gram-negative, enteropathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) is exposed to various stress conditions during pathogenesis, of which acid stress serves as a major defense mechanism in the host. Such environments are encountered in the stomach and Salmonella containing vacuole of phagocytic and non-phagocytic cells. It is only recently that small RNAs (sRNAs) have come to the forefront as major regulators of stress response networks. Consequently, the sRNA DsrA which regulates acid resistance in Escherichia coli, has not been characterized in the acid tolerance response (ATR) of Salmonella. In this study, we show dsrA to be induced two and threefold under adaptation and challenge phases of the ATR, respectively. Additionally, an isogenic mutant lacking dsrA (DeltaDsrA) displayed lower viability under the ATR along with reduced motility, feeble adhesion and defective invasion efficacy in vitro. Expression analysis revealed down regulation of several Salmonella pathogenicity island-1 (SPI-1) effectors in DeltaDsrA compared to the wild-type, under SPI-1 inducing conditions. Additionally, our in vivo data revealed DeltaDsrA to be unable to cause gut inflammation in C57BL/6 mice at 72 h post infection, although intracellular survival and systemic dissemination remained unaffected. A possible explanation may be the significantly reduced expression of flagellin structural genes fliC and fljB in DeltaDsrA, which have been implicated as major proinflammatory determinants. This study serves to highlight the role of sRNAs such as DsrA in both acid tolerance and virulence of S. Typhimurium. Additionally the robust phenotype of non-invasiveness could be exploited in developing SPI-I attenuated S. Typhimurium strains without disrupting SPI-I genes. PMID- 27199928 TI - Carbon and Sulfur Cycling below the Chemocline in a Meromictic Lake and the Identification of a Novel Taxonomic Lineage in the FCB Superphylum, Candidatus Aegiribacteria. AB - Mahoney Lake in British Columbia is an extreme meromictic system with unusually high levels of sulfate and sulfide present in the water column. As is common in strongly stratified lakes, Mahoney Lake hosts a dense, sulfide-oxidizing phototrophic microbial community where light reaches the chemocline. Below this "plate," the euxinic hypolimnion is anoxic, eutrophic, saline, and rich in sulfide, polysulfides, elemental sulfur, and other sulfur intermediates. While much is known regarding microbial communities in sunlit portions of euxinic systems, the composition and genetic potential of organisms living at aphotic depths have rarely been studied. Metagenomic sequencing of samples from the hypolimnion and the underlying sediments of Mahoney Lake indicate that multiple taxa contribute to sulfate reduction below the chemocline and that the hypolimnion and sediments each support distinct populations of sulfate reducing bacteria (SRB) that differ from the SRB populations observed in the chemocline. After assembling and binning the metagenomic datasets, we recovered near-complete genomes of dominant populations including two Deltaproteobacteria. One of the deltaproteobacterial genomes encoded a 16S rRNA sequence that was most closely related to the sulfur-disproportionating genus Dissulfuribacter and the other encoded a 16S rRNA sequence that was most closely related to the fatty acid- and aromatic acid-degrading genus Syntrophus. We also recovered two near-complete genomes of Firmicutes species. Analysis of concatenated ribosomal protein trees suggests these genomes are most closely related to extremely alkaliphilic genera Alkaliphilus and Dethiobacter. Our metagenomic data indicate that these Firmicutes contribute to carbon cycling below the chemocline. Lastly, we recovered a nearly complete genome from the sediment metagenome which represents a new genus within the FCB (Fibrobacteres, Chlorobi, Bacteroidetes) superphylum. Consistent with the geochemical data, we found little or no evidence for organisms capable of sulfide oxidation in the aphotic zone below the chemocline. Instead, comparison of functional genes below the chemocline are consistent with recovery of multiple populations capable of reducing oxidized sulfur. Our data support previous observations that at least some of the sulfide necessary to support the dense population of phototrophs in the chemocline is supplied from sulfate reduction in the hypolimnion and sediments. These studies provide key insights regarding the taxonomic and functional diversity within a euxinic environment and highlight the complexity of biogeochemical carbon and sulfur cycling necessary to maintain euxinia. PMID- 27199931 TI - Attachment Capability of Antagonistic Yeast Rhodotorula glutinis to Botrytis cinerea Contributes to Biocontrol Efficacy. AB - Rhodotorula glutinis as an antagonism show good biocontrol performance against various post-harvest diseases in fruits. In the present study, strong attachment capability of R. glutinis to spores and hyphae of Botrytis cinerea was observed. Further analysis showed that certain protein components on the yeast cell surface played critical role during the interaction between R. glutinis and B. cinerea. The components mainly distributed at the poles of yeast cells and might contain glycosylation modification, as tunicamycin treated yeast cells lost attachment capability to B. cinerea. To investigate contributions of attachment capability of R. glutinis to its biocontrol efficacy, yeast cells were mutagenized with 3% methane-sulfonic acid ethyl ester (EMS), and a mutant CE4 with stable non attaching phenotype was obtained. No significant difference was found on colony, cell morphology, reproductive ability, and capsule formation between the mutant and wild-type. However, there was a distinct difference in India ink positive staining patterns between the two strains. Moreover, wild-type strain of R. glutinis showed better performance on inhibiting spore germination and mycelial growth of B. cinerea than CE4 strain when yeast cells and B. cinerea were co cultured in vitro. In biocontrol assay, both wild-type and CE4 strains showed significant biocontrol efficacy against gray mold caused by B. cinerea in apple fruit, whereas, control effect of CE4 strain was lower than that of wild-type. Our findings provided new evidences that attachment capability of R. glutinis to B. cinerea contributed to its biocontrol efficacy. PMID- 27199932 TI - Algicidal Effects of Prodigiosin on the Harmful Algae Phaeocystis globosa. AB - Phaeocystis globosa blooms can have negative effects on higher trophic levels in the marine ecosystem and consequently influence human activities. Strain KA22, identified as the bacterium Hahella, was isolated from coastal surface water and used to control P. globosa growth. A methanol extract from the bacterial cells showed strong algicidal activity. After purification, the compound showed a similar structure to prodigiosin when identified with Q-Exactive Orbitrap MS and nuclear magnetic resonance spectra. The compound showed algicidal activity against P. globosa with a 50% Lethal Dose (LD50) of 2.24 MUg/mL. The prodigiosin was stable under heat and acid environment, and it could be degraded under alkaline environment and natural light condition. The growth rates of strain KA22 was fast in 2216E medium and the content of prodigiosin in this medium was more than 70 MUg/mL after 16 h incubation. The compound showed particularly strong algicidal activity against Prorocentrum donghaiense, P. Globosa, and Heterosigma akashiwo, but having little effect on three other phytoplankton species tested. The results of our research could increase our knowledge on harmful algal bloom control compound and lead to further study on the mechanisms of the lysis effect on harmful algae. PMID- 27199930 TI - Elucidating the Role of Effectors in Plant-Fungal Interactions: Progress and Challenges. AB - Pathogenic fungi have diverse growth lifestyles that support fungal colonization on plants. Successful colonization and infection for all lifestyles depends upon the ability to modify living host plants to sequester the necessary nutrients required for growth and reproduction. Secretion of virulence determinants referred to as "effectors" is assumed to be the key governing factor that determines host infection and colonization. Effector proteins are capable of suppressing plant defense responses and alter plant physiology to accommodate fungal invaders. This review focuses on effector molecules of biotrophic and hemibiotrophic plant pathogenic fungi, and the mechanism required for the release and uptake of effector molecules by the fungi and plant cells, respectively. We also place emphasis on the discovery of effectors, difficulties associated with predicting the effector repertoire, and fungal genomic features that have helped promote effector diversity leading to fungal evolution. We discuss the role of specific effectors found in biotrophic and hemibiotrophic fungi and examine how CRISPR/Cas9 technology may provide a new avenue for accelerating our ability in the discovery of fungal effector function. PMID- 27199935 TI - Identification of Genes Required for Secretion of the Francisella Oxidative Burst Inhibiting Acid Phosphatase AcpA. AB - Francisella tularensis is a Tier 1 bioterror threat and the intracellular pathogen responsible for tularemia in humans and animals. Upon entry into the host, Francisella uses multiple mechanisms to evade killing. Our previous studies have shown that after entering its primary cellular host, the macrophage, Francisella immediately suppresses the oxidative burst by secreting a series of acid phosphatases including AcpA-B-C and HapA, thereby evading the innate immune response of the macrophage and enhancing survival and further infection. However, the mechanism of acid phosphatase secretion by Francisella is still unknown. In this study, we screened for genes required for AcpA secretion in Francisella. We initially demonstrated that the known secretion systems, the putative Francisella pathogenicity island (FPI)-encoded Type VI secretion system and the Type IV pili, do not secrete AcpA. Using random transposon mutagenesis in conjunction with ELISA, Western blotting and acid phosphatase enzymatic assays, a transposon library of 5450 mutants was screened for strains with a minimum 1.5-fold decrease in secreted (culture supernatant) AcpA, but no defect in cytosolic AcpA. Three mutants with decreased supernatant AcpA were identified. The transposon insertion sites of these mutants were revealed by direct genomic sequencing or inverse-PCR and sequencing. One of these mutants has a severe defect in AcpA secretion (at least 85% decrease) and is a predicted hypothetical inner membrane protein. Interestingly, this mutant also affected the secretion of the FPI-encoded protein, VgrG. Thus, this screen identified novel protein secretion factors involved in the subversion of host defenses. PMID- 27199934 TI - Regulation of the Two-Component Regulator CpxR on Aminoglycosides and beta lactams Resistance in Salmonella enterica serovar Typhimurium. AB - The two-component signal transduction system CpxAR is especially widespread in Gram-negative bacteria. It has been reported that CpxAR contributes to the multidrug resistance (MDR) in Escherichia coli. CpxR is a response regulator in the two-component CpxAR system. The aim of this study was to explore the role of cpxR in the MDR of S. enterica serovar Typhimurium. The minimal inhibitory concentrations (MICs) of various antibiotics commonly used in veterinary medicine for strains JS (a multidrug-susceptible standard strain of S. enterica serovar Typhimurium), JSDeltacpxR, JSDeltacpxR/pcpxR, JSDeltacpxR/pcpxR (*), JSDeltacpxRDeltaacrB, JSDeltacpxRDeltaacrB/pcpxR, JSDeltacpxRDeltaacrB/pcpxR (*), 9 S. enterica serovar Typhimurium isolates (SH1-9), and SH1-9DeltacpxR were determined by the 2-fold broth microdilution method. The relative mRNA expression levels of ompF, ompC, ompW, ompD, tolC, acrB, acrD, acrF, mdtA, marA, and soxS in strains JS, JSDeltacpxR, and JSDeltacpxR/pcpxR were detected by real-time PCR. The results showed 2- to 4-fold decreases in the MICs of amikacin (AMK), gentamycin (GEN), apramycin (APR), neomycin (NEO), ceftriaxone (CRO), ceftiofur (CEF), and cefquinome (CEQ) for strain JSDeltacpxR, as compared to those for the parental strain JS. Likewise, SH1-9DeltacpxR were found to have 2- to 8-fold reduction in resistance to the above antibiotics, except for NEO, as compared to their parental strains SH1-9. Furthermore, 2- to 4-fold further decreases in the MICs of AMK, GEN, APR, and CEF for strain JSDeltacpxRDeltaacrB were observed, as compared to those for strain JSDeltaacrB. In addition, CpxR overproduction in strain JSDeltacpxR led to significant decreases in the mRNA expression levels of ompF, ompC, ompW, ompD, tolC, acrB, marA, and soxS, and significant increases in those of stm3031 and stm1530. Notably, after all strains were induced simultaneously by GEN to the 15th passage at subinhibitory concentrations, strain JSDeltacpxR/pcpxR showed significant increases in mRNA expression levels of the efflux pump acrD and mdtA genes, as compared to strain JSDeltacpxR. Our results indicate that the two-component regulator CpxR contributes to resistance of S. enterica serovar Typhimurium to aminoglycosides and beta-lactams by influencing the expression level of the MDR-related genes. PMID- 27199936 TI - Seasonal Succession Leads to Habitat-Dependent Differentiation in Ribosomal RNA:DNA Ratios among Freshwater Lake Bacteria. AB - Relative abundance profiles of bacterial populations measured by sequencing DNA or RNA of marker genes can widely differ. These differences, made apparent when calculating ribosomal RNA:DNA ratios, have been interpreted as variable activities of bacterial populations. However, inconsistent correlations between ribosomal RNA:DNA ratios and metabolic activity or growth rates have led to a more conservative interpretation of this metric as the cellular protein synthesis potential (PSP). Little is known, particularly in freshwater systems, about how PSP varies for specific taxa across temporal and spatial environmental gradients and how conserved PSP is across bacterial phylogeny. Here, we generated 16S rRNA gene sequencing data using simultaneously extracted DNA and RNA from fractionated (free-living and particulate) water samples taken seasonally along a eutrophic freshwater estuary to oligotrophic pelagic transect in Lake Michigan. In contrast to previous reports, we observed frequent clustering of DNA and RNA data from the same sample. Analysis of the overlap in taxa detected at the RNA and DNA level indicated that microbial dormancy may be more common in the estuary, the particulate fraction, and during the stratified period. Across spatiotemporal gradients, PSP was often conserved at the phylum and class levels. PSPs for specific taxa were more similar across habitats in spring than in summer and fall. This was most notable for PSPs of the same taxa when located in the free living or particulate fractions, but also when contrasting surface to deep, and estuary to Lake Michigan communities. Our results show that community composition assessed by RNA and DNA measurements are more similar than previously assumed in freshwater systems. However, the similarity between RNA and DNA measurements and taxa-specific PSPs that drive community-level similarities are conditional on spatiotemporal factors. PMID- 27199933 TI - Single-Cell (Meta-)Genomics of a Dimorphic Candidatus Thiomargarita nelsonii Reveals Genomic Plasticity. AB - The genus Thiomargarita includes the world's largest bacteria. But as uncultured organisms, their physiology, metabolism, and basis for their gigantism are not well understood. Thus, a genomics approach, applied to a single Candidatus Thiomargarita nelsonii cell was employed to explore the genetic potential of one of these enigmatic giant bacteria. The Thiomargarita cell was obtained from an assemblage of budding Ca. T. nelsonii attached to a provannid gastropod shell from Hydrate Ridge, a methane seep offshore of Oregon, USA. Here we present a manually curated genome of Bud S10 resulting from a hybrid assembly of long Pacific Biosciences and short Illumina sequencing reads. With respect to inorganic carbon fixation and sulfur oxidation pathways, the Ca. T. nelsonii Hydrate Ridge Bud S10 genome was similar to marine sister taxa within the family Beggiatoaceae. However, the Bud S10 genome contains genes suggestive of the genetic potential for lithotrophic growth on arsenite and perhaps hydrogen. The genome also revealed that Bud S10 likely respires nitrate via two pathways: a complete denitrification pathway and a dissimilatory nitrate reduction to ammonia pathway. Both pathways have been predicted, but not previously fully elucidated, in the genomes of other large, vacuolated, sulfur-oxidizing bacteria. Surprisingly, the genome also had a high number of unusual features for a bacterium to include the largest number of metacaspases and introns ever reported in a bacterium. Also present, are a large number of other mobile genetic elements, such as insertion sequence (IS) transposable elements and miniature inverted-repeat transposable elements (MITEs). In some cases, mobile genetic elements disrupted key genes in metabolic pathways. For example, a MITE interrupts hupL, which encodes the large subunit of the hydrogenase in hydrogen oxidation. Moreover, we detected a group I intron in one of the most critical genes in the sulfur oxidation pathway, dsrA. The dsrA group I intron also carried a MITE sequence that, like the hupL MITE family, occurs broadly across the genome. The presence of a high degree of mobile elements in genes central to Thiomargarita's core metabolism has not been previously reported in free-living bacteria and suggests a highly mutable genome. PMID- 27199937 TI - Bifidobacterium animalis ssp. lactis CNCM-I2494 Restores Gut Barrier Permeability in Chronically Low-Grade Inflamed Mice. AB - Growing evidence supports the efficacy of many probiotic strains in the management of gastrointestinal disorders associated with deregulated intestinal barrier function and/or structure. In particular, bifidobacteria have been studied for their efficacy to both prevent and treat a broad spectrum of animal and/or human gut disorders. The aim of the current work was thus to evaluate effects on intestinal barrier function of Bifidobacterium animalis ssp. lactis CNCM-I2494, a strain used in fermented dairy products. A chronic dinitrobenzene sulfonic acid (DNBS)-induced low-grade inflammation model causing gut dysfunction in mice was used in order to study markers of inflammation, intestinal permeability, and immune function in the presence of the bacterial strain. In this chronic low-grade inflammation mice model several parameters pointed out the absence of an over active inflammation process. However, gut permeability, lymphocyte populations, and colonic cytokines were found to be altered. B. animalis ssp. lactis CNCM-I2494 was able to protect barrier functions by restoring intestinal permeability, colonic goblet cell populations, and cytokine levels. Furthermore, tight junction (TJ) proteins levels were also measured by qRT-PCR showing the ability of this strain to specifically normalize the level of several TJ proteins, in particular for claudin-4. Finally, B. lactis strain counterbalanced CD4(+) lymphocyte alterations in both spleen and mesenteric lymphoid nodes. It restores the Th1/Th2 ratio altered by the DNBS challenge (which locally augments CD4(+) Th1 cells) by increasing the Th2 response as measured by the increase in the production of major representative Th2 cytokines (IL-4, IL-5, and IL-10). Altogether, these data suggest that B. animalis ssp. lactis CNCM-I2494 may efficiently prevent disorders associated with increased barrier permeability. PMID- 27199938 TI - Evaluation of Immunoprotection Conferred by the Subunit Vaccines of GRA2 and GRA5 against Acute Toxoplasmosis in BALB/c Mice. AB - Toxoplasmosis is a foodborne disease caused by Toxoplasma gondii, an obligate intracellular parasite. Severe symptoms occur in the immunocompromised patients and pregnant women leading to fatality and abortions respectively. Vaccination development is essential to control the disease. The T. gondii dense granule antigen 2 and 5 (GRA2 and GRA5) have been targeted in this study because these proteins are essential to the development of parasitophorous vacuole (PV), a specialized compartment formed within the infected host cell. PV is resistance to host cell endosomes and lysosomes thereby protecting the invaded parasite. Recombinant dense granular proteins, GRA2 (rGRA2) and GRA5 (rGRA5) were cloned, expressed, and purified in Escherichia coli, BL21 (DE3) pLysS. The potential of these purified antigens as subunit vaccine candidates against toxoplasmosis were evaluated through subcutaneous injection of BALB/c mice followed by immunological characterization (humoral- and cellular-mediated) and lethal challenge against virulent T. gondii RH strain in BALB/c mice. Results obtained demonstrated that rGRA2 and rGRA5 elicited humoral and cellular-mediated immunity in the mice. High level of IgG antibody was produced with the isotype IgG2a/IgG1 ratio of ~0.87 (p < 0.001). Significant increase (p < 0.05) in the level of four cytokines (IFN gamma, IL-2, IL-4, and IL-10) was obtained. The antibody and cytokine results suggest that a mix mode of Th1/Th2-immunity was elicited with predominant Th1 immune response inducing partial protection against T. gondii acute infection in BALB/c mice. Our findings indicated that both GRA2 and GRA5 are potential candidates for vaccine development against T. gondii acute infection. PMID- 27199939 TI - Aroma Profile of Montepulciano d'Abruzzo Wine Fermented by Single and Co-culture Starters of Autochthonous Saccharomyces and Non-saccharomyces Yeasts. AB - Montepulciano d'Abruzzo is a native grape variety of Vitis vinifera L., grown in central Italy and used for production of high quality red wines. Limited studies have been carried out to improve its enological characteristics through the use of indigenous strains of Saccharomyces cerevisiae. The main objective of the present work was to test two indigenous strains of S. cerevisiae (SRS1, RT73), a strain of Starmerella bacillaris (STS12), one of Hanseniaspora uvarum (STS45) and a co-culture of S. cerevisiae (SRS1) and S. bacillaris (STS12), in an experimental cellar to evaluate their role in the sensory characteristic of Montepulciano d'Abruzzo wine. A S. cerevisiae commercial strain was used. Fermentations were conducted under routine Montepulciano d'Abruzzo wine production, in which the main variables were the yeast strains used for fermentation. Basic winemaking parameters, some key chemical analysis and aroma compounds were considered. S. cerevisiae strain dynamics during fermentation were determined by molecular methods. The musts inoculated with the co-culture were characterized by a faster fermentation start and a higher content of glycerol after 3 days of fermentation, as well as the musts added with strains S. bacillaris (STS12) and H. uvarum (STS45). At the end of fermentation the parameters studied were quite similar in all the wines. Total biogenic amines (BA) content of all the wines was low. Ethanolamine was the predominant BA, with a concentration ranging from 21 to 24 mg/l. Wines were characterized by esters and alcohols. In particular, 2-phenylethanol, 3-methylbut-1-yl methanoate, and ethyl ethanoate were the major aroma volatile compounds in all wines. Statistical analysis highlighted the different role played by aroma compounds in the differentiation of wines, even if it was impossible to select a single class of compounds as the most important for a specific yeast. The present study represents a further step toward the use of tailored autochthonous strains to impart the specific characteristics of a given wine which are an expression of a specific terroir. PMID- 27199940 TI - A Trypsin Inhibitor from Tecoma stans Leaves Inhibits Growth and Promotes ATP Depletion and Lipid Peroxidation in Candida albicans and Candida krusei. AB - Tecoma stans (yellow elder) has shown medicinal properties and antimicrobial activity. Previous reports on antifungal activity of T. stans preparations and presence of trypsin inhibitor activity from T. stans leaves stimulated the investigation reported here. In this work, we proceeded to the purification and characterization of a trypsin inhibitor (TesTI), which was investigated for anti Candida activity. Finally, in order to determine the potential of TesTI as a new natural chemotherapeutic product, its cytotoxicity to human peripheral blood mononuclear cells (PBMCs) was evaluated. TesTI was isolated from saline extract by ammonium sulfate fractionation followed by ion exchange and gel filtration chromatographies. Antifungal activity was evaluated by determining the minimal inhibitory (MIC) and fungicide (MFC) concentrations using fungal cultures containing only yeast form or both yeast and hyphal forms. Candida cells treated with TesTI were evaluated for intracellular ATP levels and lipid peroxidation. Cytotoxicity of TesTI to PBMCs was evaluated by MTT assay. TesTI (39.8 kDa, pI 3.41, K i 43 nM) inhibited similarly the growth of both C. albicans and C. krusei culture types at MIC of 100 MUg/mL. The MFCs were 200 MUg/mL for C. albicans and C. krusei. Time-response curves revealed that TesTI (at MIC) was more effective at inhibiting the replication of C. albicans cells. At MIC, TesTI promoted reduction of ATP levels and lipid peroxidation in the Candida cells, being not cytotoxic to PBMCs. In conclusion, TesTI is an antifungal agent against C. albicans and C. krusei, without toxicity to human cells. PMID- 27199941 TI - The Amino Acid Substitution Q65H in the 2C Protein of Swine Vesicular Disease Virus Confers Resistance to Golgi Disrupting Drugs. AB - Swine vesicular disease virus (SVDV) is a porcine pathogen and a member of the species Enterovirus B within the Picornaviridae family. Brefeldin A (BFA) is an inhibitor of guanine nucleotide exchange factors of Arf proteins that induces Golgi complex disassembly and alters the cellular secretory pathway. Since BFA has been shown to inhibit the RNA replication of different enteroviruses, including SVDV, we have analyzed the effect of BFA and of golgicide A (GCA), another Golgi disrupting drug, on SVDV multiplication. BFA and GCA similarly inhibited SVDV production. To investigate the molecular basis of the antiviral effect of BFA, SVDV mutants with increased resistance to BFA were isolated. A single amino acid substitution, Q65H, in the non-structural protein 2C was found to be responsible for increased resistance to BFA. These results provide new insight into the relationship of enteroviruses with the components of the secretory pathway and on the role of SVDV 2C protein in this process. PMID- 27199943 TI - Inspection Score and Grading System for Food Services in Brazil: The Results of a Food Safety Strategy to Reduce the Risk of Foodborne Diseases during the 2014 FIFA World Cup. AB - In 2014, Brazil hosted one of the most popular sport competitions in the world, the FIFA World Cup. Concerned about the intense migration of tourists, the Brazilian government decided to deploy a food safety strategy based on inspection scores and a grading system applied to food services. The present study aimed to evaluate the results of the food safety strategy deployed during the 2014 FIFA World Cup in Brazil. To assess food safety, an evaluation instrument was applied twice in 1927 food service establishments from 26 cities before the start of the competition. This instrument generated a food safety score for each establishment that ranged from 0.0 (no flaws observed) to 2565.95, with four possible grades: A (0.0-13.2); B (13.3-502.6); C (502.7-1152.2); and pending (more than 1152.3). Each food service received a stamp with the grade of the second evaluation. After the end of the World Cup, a study was conducted with different groups of the public to evaluate the acceptance of the strategy. To this end, 221 consumers, 998 food service owners or managers, 150 health surveillance auditors, and 27 health surveillance coordinators were enrolled. These participants completed a survey with positive and negative responses about the inspection score system through a 5-point Likert scale. A reduction in violation scores from 393.1 to 224.4 (p < 0.001) was observed between the first and second evaluation cycles. Of the food services evaluated, 38.7% received the A stamp, 41.4% the B stamp, and 13.9% the C stamp. All positive responses on "system reliability" presented a mean of 4.0 or more, indicating that the public believed this strategy is reliable for communicating risks and promoting food safety. The strategy showed positive results regarding food safety and public acceptance. The deployed strategy promoted improvements in the food safety of food services. The implementation of a permanent policy may be well accepted by the public and may greatly contribute to a reduction in foodborne diseases (FBDs). PMID- 27199944 TI - Resistance Assessment for Oxathiapiprolin in Phytophthora capsici and the Detection of a Point Mutation (G769W) in PcORP1 that Confers Resistance. AB - The potential for oxathiapiprolin resistance in Phytophthora capsici was evaluated. The baseline sensitivities of 175 isolates to oxathiapiprolin were initially determinated and found to conform to a unimodal curve with a mean EC50 value of 5.61 * 10(-4) MUg/ml. Twelve stable oxathiapiprolin-resistant mutants were generated by fungicide adaptation in two sensitive isolates, LP3 and HNJZ10. The fitness of the LP3-mutants was found to be similar to or better than that of the parental isolate LP3, while the HNJZ10-mutants were found to have lost the capacity to produce zoospores. Taken together these results suggest that the risk of P. capsici developing resistance to oxathiapiprolin is moderate. Comparison of the PcORP1 genes in the LP3-mutants and wild-type parental isolate, which encode the target protein of oxathiapiprolin, revealed that a heterozygous mutation caused the amino acid substitution G769W. Transformation and expression of the mutated PcORP1-769W allele in the sensitive wild-type isolate BYA5 confirmed that the mutation in PcORP1 was responsible for the observed oxathiapiprolin resistance. Finally diagnostic tests including As-PCR and CAPs were developed to detect the oxathiapiprolin resistance resulting from the G769W point mutation in field populations of P. capsici. PMID- 27199942 TI - Effect of Biofilm Formation by Oenococcus oeni on Malolactic Fermentation and the Release of Aromatic Compounds in Wine. AB - The winemaking process involves the alcoholic fermentation of must, often followed by malolactic fermentation (MLF). The latter, mainly carried out by the lactic acid bacterium Oenococcus oeni, is used to improve wine quality when acidity reduction is required. Moreover, it prevents microbial spoilage and improves the wine's organoleptic profile. Prior observations showed that O. oeni is able to resist several months in harsh wine conditions when adhered on oak barrels. Since biofilm is a prevailing microbial lifestyle in natural environments, the capacity of O. oeni to form biofilms was investigated on winemaking material such as stainless steel and oak chips. Scanning Electron Microscopy and Confocal Laser Scanning Microscopy showed that O. oeni was able to adhere to these surfaces and form spatially organized microcolonies embedded in extracellular substances. To assess the competitive advantage of this mode of life in wine, the properties of biofilm and planktonic cells were compared after inoculation in a fermented must (pH 3.5 or 3.2 and 12% ethanol) The results indicated that the biofilm culture of O. oeni conferred (i) increased tolerance to wine stress, and (ii) functional performance with effective malolactic activities. Relative gene expression focusing on stress genes and genes involved in EPS synthesis was investigated in a mature biofilm and emphasized the role of the matrix in increased biofilm resistance. As oak is commonly used in wine aging, we focused on the O. oeni biofilm on this material and its contribution to the development of wine color and the release of aromatic compounds. Analytical chromatography was used to target the main oak aging compounds such as vanillin, gaiacol, eugenol, whisky-lactones, and furfural. The results reveal that O. oeni biofilm developed on oak can modulate the wood-wine transfer of volatile aromatic compounds during MLF and aging by decreasing furfural, gaiacol, and eugenol in particular. This work showed that O. oeni forms biofilms consisting of stress tolerant cells capable of efficient MLF under winemaking conditions. Therefore surface-associated behaviors should be considered in the development of improved strategies for the control of MLF in wine. PMID- 27199945 TI - Isolation of Oxamyl-degrading Bacteria and Identification of cehA as a Novel Oxamyl Hydrolase Gene. AB - Microbial degradation is the main process controlling the environmental dissipation of the nematicide oxamyl. Despite that, little is known regarding the microorganisms involved in its biotransformation. We report the isolation of four oxamyl-degrading bacterial strains from an agricultural soil exhibiting enhanced biodegradation of oxamyl. Multilocus sequence analysis (MLSA) assigned the isolated bacteria to different subgroups of the genus Pseudomonas. The isolated bacteria hydrolyzed oxamyl to oxamyl oxime, which was not further transformed, and utilized methylamine as a C and N source. This was further supported by the detection of methylamine dehydrogenase in three of the four isolates. All oxamyl degrading strains carried a gene highly homologous to a carbamate-hydrolase gene cehA previously identified in carbaryl- and carbofuran-degrading strains. Transcription analysis verified its direct involvement in the hydrolysis of oxamyl. Selected isolates exhibited relaxed degrading specificity and transformed all carbamates tested including the oximino carbamates aldicarb and methomyl (structurally related to oxamyl) and the aryl-methyl carbamates carbofuran and carbaryl which share with oxamyl only the carbamate moiety. PMID- 27199946 TI - Evaluation of the Effects of Photodynamic Therapy Alone and Combined with Standard Antifungal Therapy on Planktonic Cells and Biofilms of Fusarium spp. and Exophiala spp. AB - Infections of Fusarium spp. and Exophiala spp. are often chronic, recalcitrant, resulting in significant morbidity, causing discomfort, disfigurement, social isolation. Systemic disseminations happen in compromised patients, which are often refractory to available antifungal therapies and thereby lead to death. The antimicrobial photodynamic therapy (aPDT) has been demonstrated to effectively inactivate multiple pathogenic fungi and is considered as a promising alternative treatment for mycoses. In the present study, we applied methylene blue (8, 16, and 32 MUg/ml) as a photosensitizing agent and light emitting diode (635 +/- 10 nm, 12 and 24 J/cm(2)), and evaluated the effects of photodynamic inactivation on five strains of Fusarium spp. and five strains of Exophiala spp., as well as photodynamic effects on in vitro susceptibility to itraconazole, voriconazole, posaconazole and amphotericin B, both planktonic and biofilm forms. Photodynamic therapy was efficient in reducing the growth of all strains tested, exhibiting colony forming unit-reductions of up to 6.4 log10 and 5.6 log10 against planktonic cultures and biofilms, respectively. However, biofilms were less sensitive since the irradiation time was twice longer than that of planktonic cultures. Notably, the photodynamic effects against Fusarium strains with high minimal inhibitory concentration (MIC) values of >=16, 4-8, 4-8, and 2-4 MUg/ml for itraconazole, voriconazole, posaconazole and amphotericin B, respectively, were comparable or even superior to Exophiala spp., despite Exophiala spp. showed relatively better antifungal susceptibility profile. MIC ranges against planktonic cells of both species were up to 64 times lower after aPDT treatment. Biofilms of both species showed high sessile MIC50 (SMIC50) and SMIC80 of >=16 MUg/ml for all azoles tested and variable susceptibilities to amphotericin B, with SMIC ranging between 1 and 16 MUg/ml. Biofilms subjected to aPDT exhibited a distinct reduction in SMIC50 and SMIC80 compared to untreated groups for both species, except SMIC80 of itraconazole against Fusarium biofilms. In conclusion, in vitro photodynamic therapy was efficient in inactivation of Fusarium spp. and Exophiala spp., both planktonic cultures and biofilms. In addition, the combination of aPDT and antifungal drugs represents an attractive alternative to the current antifungal strategies. However, further investigations are warranted for the reliable and safe application in clinical practice. PMID- 27199947 TI - Multi-Fluorescence Real-Time PCR Assay for Detection of RIF and INH Resistance of M. tuberculosis. AB - BACKGROUND: Failure to early detect multidrug-resistant tuberculosis (MDR-TB) results in treatment failure and poor clinical outcomes, and highlights the need to rapidly detect resistance to rifampicin (RIF) and isoniazid (INH). METHODS: In Multi-Fluorescence quantitative Real-Time PCR (MF-qRT-PCR) assay, 10 probes labeled with four kinds of fluorophores were designed to detect the mutations in regions of rpoB, katG, mabA-inhA, oxyR-ahpC, and rrs. The efficiency of MF-qRT PCR assay was tested using 261 bacterial isolates and 33 clinical sputum specimens. Among these samples, 227 Mycobacterium tuberculosis isolates were analyzed using drug susceptibility testing (DST), DNA sequencing and MF-qRT-PCR assay. RESULTS: Compared with DST, MF-qRT-PCR sensitivity and specificity for RIF resistance were 94.6 and 100%, respectively. And the detection sensitivity and specificity for INH-resistance were 85.9 and 95.3%, respectively. Compared with DNA sequencing, the sensitivity and specificity of our assay were 97.2 and 100% for RIF-resistance and 97.9 and 96.4% for INH-resistance. Compared with Phenotypic strain identification, MF-qRT-PCR can distinguish 227 M. tuberculosis complexes (MTC) from 34 Non-tuberculous mycobacteria (NTM) isolates with 100% accuracy rate. CONCLUSIONS: MF-qRT-PCR assay was an efficient, accurate, reliable, and easy-operated method for detection of RIF and INH-resistance, and distinction of MTC and NTM of clinical isolates. PMID- 27199949 TI - Exploring the Synergy between Cellobiose Dehydrogenase from Phanerochaete chrysosporium and Cellulase from Trichoderma reesei. AB - Recent demands for the production of lignocellulose biofuels boosted research on cellulase. Hydrolysis efficiency and production cost of cellulase are two bottlenecks in "biomass to biofuels" process. The Trichoderma cellulase mixture is one of the most commonly used enzymes for cellulosic hydrolysis. During hydrolytic process cellobiose accumulation causes feedback inhibition against most cellobiohydrolases and endoglucanases. In this study, we demonstrated the synergism effects between cellobiose dehydrogenase (CDH) and cellulase both in vitro and in vivo. The CDH from Phanerochaete chrysosporium was heterologously expressed in Pichia pastoris. Supplementation of the purified CDH in Trichoderma cellulase increased the cellulase activities. Especially beta-glucosidase activity was increased by 30-100% varying at different time points. On the other hand, the cdh gene was heterologously expressed in Trichoderma reesei to explore the synergism between CDH and cellulases in vivo. The analyses of gene expression and enzymatic profiles of filter paper activity, carboxymethylcellulase (CMCase) and beta-glucosidase show the increased cellulase activity and the enhanced cellulase production in the cdh-expressing strains. The results elucidate a possible mechanism for diminishing the cellobiose inhibition of cellulase by CDH. These findings provide a novel perspective to make more economic enzyme cocktails for commercial application or explore alternative strategies for generating cellulase-producing strains with higher efficiency. PMID- 27199948 TI - Genome-Wide Detection of Predicted Non-coding RNAs Related to the Adhesion Process in Vibrio alginolyticus Using High-Throughput Sequencing. AB - The ability of bacteria to adhere to fish mucus can be affected by environmental conditions and is considered to be a key virulence factor of Vibrio alginolyticus. However, the molecular mechanism underlying this ability remains unclear. Our previous study showed that stress conditions such as exposure to Cu, Pb, Hg, and low pH are capable of reducing the adhesion ability of V. alginolyticus. Non-coding RNAs (ncRNAs) play a crucial role in the intricate regulation of bacterial gene expression, thereby affecting bacterial pathogenicity. Thus, we hypothesized that ncRNAs play a key role in the V. alginolyticus adhesion process. To validate this, we combined high-throughput sequencing with computational techniques to detect ncRNA dynamics in samples after stress treatments. The expression of randomly selected novel ncRNAs was confirmed by QPCR. Among the significantly altered ncRNAs, 30 were up-regulated and 2 down-regulated by all stress treatments. The QPCR results reinforced the reliability of the sequencing data. Target prediction and KEGG pathway analysis indicated that these ncRNAs are closely related to pathways associated with in vitro adhesion, and our results indicated that chemical stress-induced reductions in the adhesion ability of V. alginolyticus might be due to the perturbation of ncRNA expression. Our findings provide important information for further functional characterization of ncRNAs during the adhesion process of V. alginolyticus. PMID- 27199950 TI - Efflux Pump Blockers in Gram-Negative Bacteria: The New Generation of Hydantoin Based-Modulators to Improve Antibiotic Activity. AB - Multidrug resistant (MDR) bacteria are an increasing health problem with the shortage of new active antibiotic agents. Among effective mechanisms that contribute to the spread of MDR Gram-negative bacteria are drug efflux pumps that expel clinically important antibiotic classes out of the cell. Drug pumps are attractive targets to restore the susceptibility toward the expelled antibiotics by impairing their efflux activity. Arylhydantoin derivatives were investigated for their potentiation of activities of selected antibiotics described as efflux substrates in Enterobacter aerogenes expressing or not AcrAB pump. Several compounds increased the bacterial susceptibility toward nalidixic acid, chloramphenicol and sparfloxacin and were further pharmacomodulated to obtain a better activity against the AcrAB producing bacteria. PMID- 27199951 TI - A High-resolution Typing Assay for Uropathogenic Escherichia coli Based on Fimbrial Diversity. AB - Urinary tract infections (UTIs) are one of the most common bacterial infections in humans, causing cystitis, pyelonephritis, and renal failure. Uropathogenic Escherichia coli (UPEC) is the leading cause of UTIs. Accurate and rapid discrimination of UPEC lineages is useful for epidemiological surveillance. Fimbriae are necessary for the adherence of UPEC strains to host uroepithelia, and seem to be abundant and diverse in UPEC strains. By analyzing all the possible fimbrial operons in UPEC strains, we found that closely related strains had similar types of chaperone-usher fimbriae, and the diversity of fimbrial genes was higher than that of multilocus sequence typing (MLST) genes. A typing assay based on the polymorphism of four gene sequences (three fimbrial genes and one housekeeping gene) and the diversity of fimbriae present was developed. By comparison with the MLST, whole-genome sequence (WGS) and fumC/fimH typing methods, this was shown to be accurate and have high resolution, and it was also relatively inexpensive and easy to perform. The assay can supply more discriminatory information for UPEC lineages, and have the potential to be applied in epidemiological surveillance of UPEC isolates. PMID- 27199952 TI - Genome Structure of the Symbiont Bifidobacterium pseudocatenulatum CECT 7765 and Gene Expression Profiling in Response to Lactulose-Derived Oligosaccharides. AB - Bifidobacterium pseudocatenulatum CECT 7765 was isolated from stools of a breast fed infant. Although, this strain is generally considered an adult-type bifidobacterial species, it has also been shown to have pre-clinical efficacy in obesity models. In order to understand the molecular basis of its adaptation to complex carbohydrates and improve its potential functionality, we have analyzed its genome and transcriptome, as well as its metabolic output when growing in galacto-oligosaccharides derived from lactulose (GOS-Lu) as carbon source. B. pseudocatenulatum CECT 7765 shows strain-specific genome regions, including a great diversity of sugar metabolic-related genes. A preliminary and exploratory transcriptome analysis suggests candidate over-expression of several genes coding for sugar transporters and permeases; furthermore, five out of seven beta galactosidases identified in the genome could be activated in response to GOS-Lu exposure. Here, we also propose that a specific gene cluster is involved in controlling the import and hydrolysis of certain di- and tri-saccharides, which seemed to be those primarily taken-up by the bifidobacterial strain. This was discerned from mass spectrometry-based quantification of different saccharide fractions of culture supernatants. Our results confirm that the expression of genes involved in sugar transport and metabolism and in the synthesis of leucine, an amino acid with a key role in glucose and energy homeostasis, was up-regulated by GOS-Lu. This was done using qPCR in addition to the exploratory information derived from the single-replicated RNAseq approach, together with the functional annotation of genes predicted to be encoded in the B. pseudocatenulatum CETC 7765 genome. PMID- 27199953 TI - Antibacterial Effect of Copper on Microorganisms Isolated from Bovine Mastitis. AB - The antimicrobial properties of copper have been recognized for several years; applying these properties to the prevention of diseases such as bovine mastitis is a new area of research. The aim of the present study was to evaluate in vitro the antimicrobial activity of copper on bacteria isolated from subclinical and clinical mastitis milk samples from two regions in Chile. A total of 327 microorganisms were recovered between March and September 2013, with different prevalence by sample origin (25 and 75% from the central and southern regions of Chile, respectively). In the central region, Escherichia coli and coagulase negative Staphylococci (CNS) were the most frequently detected in clinical mastitis cases (33%), while in the southern region S. uberis, S. aureus, and CNS were detected with frequencies of 22, 21, and 18%, respectively. Antibiotic susceptibility studies revealed that 34% of isolates were resistant to one or more antibiotics and the resistance profile was different between bacterial species and origins of isolation of the bacteria. The minimum inhibitory concentration of copper (MIC-Cu) was evaluated in all the isolates; results revealed that a concentration as low as 250 ppm copper was able to inhibit the great majority of microorganisms analyzed (65% of isolates). The remaining isolates showed a MIC-Cu between 375 and 700 ppm copper, and no growth was observed at 1000 ppm. A linear relationship was found between the logarithm of viable bacteria number and time of contact with copper. With the application of the same concentration of copper (250 ppm), CNS showed the highest tolerance to copper, followed by S. uberis and S. aureus; the least resistant was E. coli. Based on these in vitro results, copper preparations could represent a good alternative to dipping solutions, aimed at preventing the presence and multiplication of potentially pathogenic microorganisms involved in bovine mastitis disease. PMID- 27199955 TI - The incC Sequence Is Required for R27 Plasmid Stability. AB - IncHI plasmids account for multiple antimicrobial resistance in Salmonella and other enterobacterial genera. These plasmids are generally very stable in their bacterial hosts. R27 is the archetype of IncHI1 plasmids. A high percentage of the R27-encoded open reading frames (ORFs) (66.7%) do not show similarity to any known ORFs. We performed a deletion analysis of all non-essential R27 DNA sequences to search for hitherto non-identified plasmid functions that might be required for plasmid stability. We report the identification of a short DNA sequence (incC) that is essential for R27 stability. That region contains several repeats (incC repeats), belongs to one of the three-plasmid replicons (R27 FIA like) and is targeted by the R27 E protein. Deletion of the incC sequence drastically reduces R27 stability both in Escherichia coli and in Salmonella, the effect being more pronounced in this latter species. Interfering with incC-E protein interaction must lead to a reduced IncHI1 plasmid stability, and may represent a new approach to combat antimicrobial resistance. PMID- 27199954 TI - The Knowns Unknowns: Exploring the Homologous Recombination Repair Pathway in Toxoplasma gondii. AB - Toxoplasma gondii is an apicomplexan parasite of medical and veterinary importance which causes toxoplasmosis in humans. Great effort is currently being devoted toward the identification of novel drugs capable of targeting such illness. In this context, we believe that the thorough understanding of the life cycle of this model parasite will facilitate the identification of new druggable targets in T. gondii. It is important to exploit the available knowledge of pathways which could modulate the sensitivity of the parasite to DNA damaging agents. The homologous recombination repair (HRR) pathway may be of particular interest in this regard as its inactivation sensitizes other cellular models such as human cancer to targeted therapy. Herein we discuss the information available on T. gondii's HRR pathway from the perspective of its conservation with respect to yeast and humans. Special attention was devoted to BRCT domain-containing and end-resection associated proteins in T. gondii as in other experimental models such proteins have crucial roles in early/late steps or HRR and in the pathway choice for double strand break resolution. We conclude that T. gondii HRR pathway is a source of several lines of investigation that allow to to comprehend the extent of diversification of HRR in T. gondii. Such an effort will serve to determine if HRR could represent a potential targer for the treatment of toxoplasmosis. PMID- 27199958 TI - Metabolic Engineering of Fusarium oxysporum to Improve Its Ethanol-Producing Capability. AB - Fusarium oxysporum is one of the few filamentous fungi capable of fermenting ethanol directly from plant cell wall biomass. It has the enzymatic toolbox necessary to break down biomass to its monosaccharides and, under anaerobic and microaerobic conditions, ferments them to ethanol. Although these traits could enable its use in consolidated processes and thus bypass some of the bottlenecks encountered in ethanol production from lignocellulosic material when Saccharomyces cerevisiae is used-namely its inability to degrade lignocellulose and to consume pentoses-two major disadvantages of F. oxysporum compared to the yeast-its low growth rate and low ethanol productivity-hinder the further development of this process. We had previously identified phosphoglucomutase and transaldolase, two major enzymes of glucose catabolism and the pentose phosphate pathway, as possible bottlenecks in the metabolism of the fungus and we had reported the effect of their constitutive production on the growth characteristics of the fungus. In this study, we investigated the effect of their constitutive production on ethanol productivity under anaerobic conditions. We report an increase in ethanol yield and a concomitant decrease in acetic acid production. Metabolomics analysis revealed that the genetic modifications applied did not simply accelerate the metabolic rate of the microorganism; they also affected the relative concentrations of the various metabolites suggesting an increased channeling toward the chorismate pathway, an activation of the gamma aminobutyric acid shunt, and an excess in NADPH regeneration. PMID- 27199956 TI - The Pmt2p-Mediated Protein O-Mannosylation Is Required for Morphogenesis, Adhesive Properties, Cell Wall Integrity and Full Virulence of Magnaporthe oryzae. AB - Protein O-mannosylation is a type of O-glycosylation that is characterized by the addition of mannose residues to target proteins, and is initially catalyzed by evolutionarily conserved protein O-mannosyltransferases (PMTs). In this study, three members of PMT were identified in Magnaporthe oryzae, and the pathogenic roles of MoPmt2, a member of PMT2 subfamily, were analyzed. We found that MoPmt2 is a homolog of Saccharomyces cerevisiae Pmt2 and could complement yeast Pmt2 function in resistance to CFW. Quantitative RT-PCR revealed that MoPmt2 is highly expressed during conidiation, and targeted disruption of MoPmt2 resulted in defects in conidiation and conidia morphology. The MoPmt2 mutants also showed a distinct reduction in fungal growth, which was associated with severe alterations in hyphal polarity. In addition, we found that the MoPmt2 mutants severely reduced virulence on both rice plants and barley leaves. The subsequent examination revealed that the fungal adhesion, conidial germination, CWI and invasive hyphae growth in host cells are responsible for defects on appressorium mediated penetration, and thus attenuated the pathogenicity of MoPmt2 mutants. Taken together, our results suggest that protein O-mannosyltransferase MoPmt2 plays essential roles in fungal growth and development, and is required for the full pathogenicity of M. oryzae. PMID- 27199957 TI - Temperature Significantly Affects the Plaquing and Adsorption Efficiencies of Listeria Phages. AB - Listeria-infecting phages are currently being used to control and detect the important foodborne pathogen Listeria monocytogenes; however, the influence of environmental conditions on the interactions between L. monocytogenes and its phages has not been explored in depth. Here, we examined the infective potential of four Listeria phages (two each from the P70-like and P100-like phages of Listeria) against five strains of L. monocytogenes (representing serotypes 1/2a, 1/2b, 4a, and 4b) grown under a range of temperatures (7-37 degrees C). We show that the plaquing efficiencies for all four phages were significantly affected by temperature. Interestingly, no plaques were observed for any of the four phages at 37 degrees C. Adsorption assays performed with the P100-like phages, LP-048 and LP-125, showed that LP-048 had a severely reduced adsorption efficiency against susceptible strains at 37 degrees C as compared to 30 degrees C, suggesting that there is considerably less accessible rhamnose (LP-048's putative phage receptor) on the host at 37 degrees C than at 30 degrees C. LP-125 adsorbed to host cells at 37 degrees C, indicating that the inability for LP-125 to plaque at 37 degrees C is not due to adsorption inhibition. LP-048 showed significantly higher adsorption efficiency against a mutant strain lacking N-acetylglucosamine in its wall teichoic acids (WTA) than the parental strain at both 30 and 37 degrees C, suggesting that N-acetylglucosamine competes with rhamnose for glycosylation sites on the WTA. The data presented here clearly shows that L. monocytogenes can gain physiological refuge from phage infection, which should be carefully considered for both the design and implementation of phage-based control and detection applications. PMID- 27199959 TI - Nitrogen Stimulates the Growth of Subsurface Basalt-associated Microorganisms at the Western Flank of the Mid-Atlantic Ridge. AB - Oceanic crust constitutes the largest aquifer system on Earth, and microbial activity in this environment has been inferred from various geochemical analyses. However, empirical documentation of microbial activity from subsurface basalts is still lacking, particularly in the cool (<25 degrees C) regions of the crust, where are assumed to harbor active iron-oxidizing microbial communities. To test this hypothesis, we report the enrichment and isolation of crust-associated microorganisms from North Pond, a site of relatively young and cold basaltic basement on the western flank of the Mid-Atlantic Ridge that was sampled during Expedition 336 of the Integrated Ocean Drilling Program. Enrichment experiments with different carbon (bicarbonate, acetate, methane) and nitrogen (nitrate and ammonium) sources revealed significant cell growth (one magnitude higher cell abundance), higher intracellular DNA content, and increased Fe(3+)/SigmaFe ratios only when nitrogen substrates were added. Furthermore, a Marinobacter strain with neutrophilic iron-oxidizing capabilities was isolated from the basalt. This work reveals that basalt-associated microorganisms at North Pond had the potential for activity and that microbial growth could be stimulated by in vitro nitrogen addition. Furthermore, iron oxidation is supported as an important process for microbial communities in subsurface basalts from young and cool ridge flank basement. PMID- 27199960 TI - Experimental Evolution on a Wild Mammal Species Results in Modifications of Gut Microbial Communities. AB - Comparative studies have shown that diet, life history, and phylogeny interact to determine microbial community structure across mammalian hosts. However, these studies are often confounded by numerous factors. Selection experiments offer unique opportunities to validate conclusions and test hypotheses generated by comparative studies. We used a replicated, 15-generation selection experiment on bank voles (Myodes glareolus) that have been selected for high swim-induced aerobic metabolism, predatory behavior toward crickets, and the ability to maintain body mass on a high-fiber, herbivorous diet. We predicted that selection on host performance, mimicking adaptive radiation, would result in distinct microbial signatures. We collected foregut and cecum samples from animals that were all fed the same nutrient-rich diet and had not been subjected to any performance tests. We conducted microbial inventories of gut contents by sequencing the V4 region of the 16S rRNA gene. We found no differences in cecal microbial community structure or diversity between control lines and the aerobic or predatory lines. However, the cecal chambers of voles selected for herbivorous capability harbored distinct microbial communities that exhibited higher diversity than control lines. The foregut communities of herbivorous-selected voles were also distinct from control lines. Overall, this experiment suggests that differences in microbial communities across herbivorous mammals may be evolved, and not solely driven by current diet or other transient factors. PMID- 27199961 TI - Pathogenicity, Transmission and Antigenic Variation of H5N1 Highly Pathogenic Avian Influenza Viruses. AB - H5N1 highly pathogenic avian influenza (HPAI) was one of the most important avian diseases in poultry production of China, especially in Guangdong province. In recent years, new H5N1 highly pathogenic avian influenza viruses (HPAIV) still emerged constantly, although all poultry in China were immunized with H5N1 vaccinations compulsorily. To better understand the pathogenicity and transmission of dominant clades of the H5N1 HPAIVs in chicken from Guangdong in 2012, we chose a clade 7.2 avian influenza virus named A/Chicken/China/G2/2012(H5N1) (G2) and a clade 2.3.2.1 avian influenza virus named A/Duck/China/G3/2012(H5N1) (G3) in our study. Our results showed that the chickens inoculated with 10(3) EID50 of G2 or G3 viruses all died, and the titers of virus replication detected in several visceral organs were high but different. In the naive contact groups, virus shedding was not detected in G2 group and all chickens survived, but virus shedding was detected in G3 group and all chickens died. These results showed that the two clades of H5N1 HPAIVs had high pathogenicity in chickens and the contact transmission of them was different in chickens. The results of cross reactive HI assay showed that antigens of G2 and G3 were very different from those of current commercial vaccines isolates (Re-4, Re-6, and D7). And to evaluate the protective efficacy of three vaccines against most isolates form Guangdong belonging to clade 2.3.2.1 in 2012, G3 was chosen to challenge the three vaccines such as Re-4, Re-6, and D7. First, chickens were immunized with 0.3 ml Re-4, Re-6, and D7 inactivated vaccines by intramuscular injection, respectively, and then challenged with 10(6) EID50 of G3 on day 28 post-vaccination. The D7 vaccine had 100% protection against G3 for chickens, the Re-6 vaccine had 88.9%, and the Re-4 vaccine only had 66.7%. Our results suggested that the D7 vaccine could prevent and control H5N1 virus outbreaks more effectively in Guangdong. From the above, it was necessary to conduct continuously epidemiological survey and study the pathogenicity and antigenic variation of avian influenza in Southern China. PMID- 27199963 TI - Expression of Immune-Related Genes of Ducks Infected with Avian Pathogenic Escherichia coli (APEC). AB - Avian pathogenic Escherichia coli (APEC) can cause severe disease in ducks, characterized by perihepatitis, pericarditis, and airsacculitis. Although the studies of bacteria isolation and methods of detection have been reported, host immune responses to APEC infection remain unclear. In response, we systemically examined the expression of immune-related genes and bacteria distribution in APEC infected ducks. Results demonstrated that APEC can quickly replicate in the liver, spleen, and brain, with the highest bacteria content at 2 days post infection. The expression of toll-like receptors (TLRs), avian beta-defensins (AvBDs) and major histocompatibility complex (MHC) were tested in the liver, spleen, and brain of infected ducks. TLR2, TLR4, TLR5, and TLR15 showed different expression patterns, which indicated that they all responded to APEC infection. The expression of AvBD2 was upregulated in all tested tissues during the 3 days of testing, whereas the expression of AvBD4, AvBD5, AvBD7, and AvBD9 were downregulated, and though MHC-I was upregulated on all test days, MHC-II was dramatically downregulated. Overall, our results suggest that APEC can replicate in various tissues in a short time, and the activation of host immune responses begins at onset of infection. These findings thus clarify duck immune responses to APEC infection and offer insights into its pathogenesis. PMID- 27199962 TI - Transcriptomic Analysis Reveals Adaptive Responses of an Enterobacteriaceae Strain LSJC7 to Arsenic Exposure. AB - Arsenic (As) resistance determinant ars operon is present in many bacteria and has been demonstrated to enhance As(V) resistance of bacteria. However, whole molecular mechanism adaptations of bacteria in response to As(V) stress remain largely unknown. In this study, transcriptional profiles of Enterobacteriaceae strain LSJC7 responding to As(V) stress were analyzed using RNA-seq and qRT-PCR. As expected, genes involved in As(V) uptake were down-regulated, those involved in As(V) reduction and As(III) efflux were up-regulated, which avoided cellular As accumulation. Reactive oxygen species and nitric oxide (NO) were induced, which caused cellular damages including DNA, protein, and Fe-S cluster damage in LSJC7. The expression of specific genes encoding transcriptional regulators, such as nsrR and soxRS were also induced. NsrR and SoxRS modulated many critical metabolic activities in As(V) stressed LSJC7 cells, including reactive species scavenging and repairing damaged DNA, proteins, and Fe-S clusters. Therefore, besides As uptake, reduction, and efflux; oxidative stress defense and damage repair were the main cellular adaptive responses of LSJC7 to As(V) stress. PMID- 27199964 TI - Potential Impact of the Resistance to Quaternary Ammonium Disinfectants on the Persistence of Listeria monocytogenes in Food Processing Environments. AB - The persistence of certain strains of Listeria monocytogenes, even after the food processing environment has been cleaned and disinfected, suggests that this may be related to phenomena that reduce the concentration of the disinfectants to subinhibitory levels. This includes (i) the existence of environmental niches or reservoirs that are difficult for disinfectants to reach, (ii) microorganisms that form biofilms and create microenvironments in which adequate concentrations of disinfectants cannot be attained, and (iii) the acquisition of resistance mechanisms in L. monocytogenes, including those that lead to a reduction in the intracellular concentration of the disinfectants. The only available data with regard to the resistance of L. monocytogenes to disinfectants applied in food production environments refer to genotypic resistance to quaternary ammonium compounds (QACs). Although there are several well-characterized efflux pumps that confer resistance to QACs, it is a low-level resistance that does not generate resistance to QACs at the concentrations applied in the food industry. However, dilution in the environment and biodegradation result in QAC concentration gradients. As a result, the microorganisms are frequently exposed to subinhibitory concentrations of QACs. Therefore, the low-level resistance to QACs in L. monocytogenes may contribute to its environmental adaptation and persistence. In fact, in certain cases, the relationship between low-level resistance and the environmental persistence of L. monocytogenes in different food production chains has been previously established. The resistant strains would have survival advantages in these environments over sensitive strains, such as the ability to form biofilms in the presence of increased biocide concentrations. PMID- 27199966 TI - Prevalence of Escherichia coli Virulence Genes in Patients with Diarrhea and a Subpopulation of Healthy Volunteers in Madrid, Spain. AB - Etiological diagnosis of diarrheal diseases may be complicated by their multi factorial nature. In addition, Escherichia coli strains present in the gut can occasionally harbor virulence genes (VGs) without causing disease, which complicates the assessment of their clinical significance in particular. The aim of this study was to detect and quantify nine VGs (stx1, stx2, eae, aggR, ehxA, invA, est, elt and bfpA) typically present in five E. coli enteric pathotypes [enterohaemorrhagic E. coli (EHEC), enterotoxigenic E. coli (ETEC), enteropathogenic E. coli (EPEC), enteroaggregative E. coli (EAEC), and enteroinvasive E. coli (EIEC)] in fecal samples collected from 49 patients with acute diarrhea and 32 healthy controls from Madrid, Spain. In addition, the presence of four serotype-related genes (wzx O104 and fliCH4, rfb O157, and fliCH7) was also determined. Presence of target genes was assessed using a quantitative real-time PCR assay previously developed, and the association of presence and burden of VGs with clinical disease and/or other risk factors was explored. Prevalence of ehxA [typically associated with Shigatoxin producing E. coli (STEC) and (EPEC), invA (EIEC), and the rfb O157+fliCH7 (STEC)] combination were significantly (p < 0.02) higher in the diarrheic group, while the wzx O104+fliCH4 combination was significantly (p = 0.014) more prevalent in the control group. On the other hand, eae was detected in more than 90% of the individuals in both patient and control populations, and it was not associated with bfpA, suggesting the absence of typical EPEC. No significant differences in the quantitative values were detected for any VG among study groups, but the difference in the load of aggR (EAEC) and invA in the patients with respect to the controls was close to the significance, suggesting a potential role of these VGs in the clinical signs observed when they are present at high levels. PMID- 27199965 TI - Virulence Characterisation of Salmonella enterica Isolates of Differing Antimicrobial Resistance Recovered from UK Livestock and Imported Meat Samples. AB - Salmonella enterica is a foodborne zoonotic pathogen of significant public health concern. We have characterized the virulence and antimicrobial resistance gene content of 95 Salmonella isolates from 11 serovars by DNA microarray recovered from UK livestock or imported meat. Genes encoding resistance to sulphonamides (sul1, sul2), tetracycline [tet(A), tet(B)], streptomycin (strA, strB), aminoglycoside (aadA1, aadA2), beta-lactam (bla TEM), and trimethoprim (dfrA17) were common. Virulence gene content differed between serovars; S. Typhimurium formed two subclades based on virulence plasmid presence. Thirteen isolates were selected by their virulence profile for pathotyping using the Galleria mellonella pathogenesis model. Infection with a chicken invasive S. Enteritidis or S. Gallinarum isolate, a multidrug resistant S. Kentucky, or a S. Typhimurium DT104 isolate resulted in high mortality of the larvae; notably presence of the virulence plasmid in S. Typhimurium was not associated with increased larvae mortality. Histopathological examination showed that infection caused severe damage to the Galleria gut structure. Enumeration of intracellular bacteria in the larvae 24 h post-infection showed increases of up to 7 log above the initial inoculum and transmission electron microscopy (TEM) showed bacterial replication in the haemolymph. TEM also revealed the presence of vacuoles containing bacteria in the haemocytes, similar to Salmonella containing vacuoles observed in mammalian macrophages; although there was no evidence from our work of bacterial replication within vacuoles. This work shows that microarrays can be used for rapid virulence genotyping of S. enterica and that the Galleria animal model replicates some aspects of Salmonella infection in mammals. These procedures can be used to help inform on the pathogenicity of isolates that may be antibiotic resistant and have scope to aid the assessment of their potential public and animal health risk. PMID- 27199967 TI - Non-conventional Yeast Species for Lowering Ethanol Content of Wines. AB - Rising sugar content in grape must, and the concomitant increase in alcohol levels in wine, are some of the main challenges affecting the winemaking industry nowadays. Among the several alternative solutions currently under study, the use of non-conventional yeasts during fermentation holds good promise for contributing to relieve this problem. Non-Saccharomyces wine yeast species comprise a high number or species, so encompassing a wider physiological diversity than Saccharomyces cerevisiae. Indeed, the current oenological interest of these microorganisms was initially triggered by their potential positive contribution to the sensorial complexity of quality wines, through the production of aroma and other sensory-active compounds. This diversity also involves ethanol yield on sugar, one of the most invariant metabolic traits of S. cerevisiae. This review gathers recent research on non-Saccharomyces yeasts, aiming to produce wines with lower alcohol content than those from pure Saccharomyces starters. Critical aspects discussed include the selection of suitable yeast strains (considering there is a noticeable intra-species diversity for ethanol yield, as shown for other fermentation traits), identification of key environmental parameters influencing ethanol yields (including the use of controlled oxygenation conditions), and managing mixed fermentations, by either the sequential or simultaneous inoculation of S. cerevisiae and non-Saccharomyces starter cultures. The feasibility, at the industrial level, of using non Saccharomyces yeasts for reducing alcohol levels in wine will require an improved understanding of the metabolism of these alternative yeast species, as well as of the interactions between different yeast starters during the fermentation of grape must. PMID- 27199969 TI - The Microbiota and Health Promoting Characteristics of the Fermented Beverage Kefir. AB - Kefir is a complex fermented dairy product created through the symbiotic fermentation of milk by lactic acid bacteria and yeasts contained within an exopolysaccharide and protein complex called a kefir grain. As with other fermented dairy products, kefir has been associated with a range of health benefits such as cholesterol metabolism and angiotensin-converting enzyme (ACE) inhibition, antimicrobial activity, tumor suppression, increased speed of wound healing, and modulation of the immune system including the alleviation of allergy and asthma. These reports have led to increased interest in kefir as a focus of research and as a potential probiotic-containing product. Here, we review those studies with a particular emphasis on the microbial composition and the health benefits of the product, as well as discussing the further development of kefir as an important probiotic product. PMID- 27199968 TI - Advances in Molecular Serotyping and Subtyping of Escherichia coli. AB - Escherichia coli plays an important role as a member of the gut microbiota; however, pathogenic strains also exist, including various diarrheagenic E. coli pathotypes and extraintestinal pathogenic E. coli that cause illness outside of the GI-tract. E. coli have traditionally been serotyped using antisera against the ca. 186 O-antigens and 53 H-flagellar antigens. Phenotypic methods, including bacteriophage typing and O- and H- serotyping for differentiating and characterizing E. coli have been used for many years; however, these methods are generally time consuming and not always accurate. Advances in next generation sequencing technologies have made it possible to develop genetic-based subtyping and molecular serotyping methods for E. coli, which are more discriminatory compared to phenotypic typing methods. Furthermore, whole genome sequencing (WGS) of E. coli is replacing established subtyping methods such as pulsed-field gel electrophoresis, providing a major advancement in the ability to investigate food borne disease outbreaks and for trace-back to sources. A variety of sequence analysis tools and bioinformatic pipelines are being developed to analyze the vast amount of data generated by WGS and to obtain specific information such as O and H-group determination and the presence of virulence genes and other genetic markers. PMID- 27199971 TI - An Innovative Method for Rapid Identification and Detection of Vibrio alginolyticus in Different Infection Models. AB - Vibrio alginolyticus is one of the most common pathogenic marine Vibrio species, and has been found to cause serious seafood-poisoning or fatal extra-intestinal infections in humans, such as necrotizing soft-tissue infections, bacteremia, septic shock, and multiple organ failures. Delayed accurate diagnosis and treatment of most Vibrio infections usually result to high mortality rates. The objective of this study was to establish a rapid diagnostic method to detect and identify the presence of V. alginolyticus in different samples, so as to facilitate timely treatment. The widely employed conventional methods for detection of V. alginolyticus include biochemical identification and a variety of PCR methods. The former is of low specificity and time-consuming (2-3 days), while the latter has improved accuracy and processing time. Despite such advancements, these methods are still complicated, time-consuming, expensive, require expertise and advanced laboratory systems, and are not optimal for field use. With the goal of providing a simple and efficient way to detect V. alginolyticus, we established a rapid diagnostic method based on loop-mediated Isothermal amplification (LAMP) technology that is feasible to use in both experimental and field environments. Three primer pairs targeting the toxR gene of V. alginolyticus were designed, and amplification was carried out in an ESE tube scanner and Real-Time PCR device. We successfully identified 93 V. alginolyticus strains from a total of 105 different bacterial isolates and confirmed their identity by 16s rDNA sequencing. We also applied this method on infected mouse blood and contaminated scallop samples, and accurate results were both easily and rapidly (20-60 min) obtained. Therefore, the RT-LAMP assay we developed can be conveniently used to detect the presence of V. alginolyticus in different samples. Furthermore, this method will also fulfill the gap for real time screening of V. alginolyticus infections especially while on field. PMID- 27199972 TI - The PK/PD Interactions of Doxycycline against Mycoplasma gallisepticum. AB - Mycoplasma gallisepticum is one of the most important pathogens that cause chronic respiratory disease in chicken. This study investigated the antibacterial activity of doxycycline against M. gallisepticum strain S6. In static time killing studies with constant antibiotic concentrations [0-64 minimum inhibitory concentration (MIC)], M. gallisepticum colonies were quantified and kill rates were calculated to estimate the drug effect. The half-life of doxycycline in chicken was 6.51 +/- 0.63 h. An in vitro dynamic model (the drug concentrations are fluctuant) was also established and two half-lives of 6.51 and 12 h were simulated. The samples were collected for drug concentration determination and viable counting of M. gallisepticum. In static time-killing studies, doxycycline produced a maximum antimycoplasmal effect of 5.62log10 (CFU/mL) reduction and the maximum kill rate was 0.11 h(-1). In the in vitro dynamic model, doxycycline had a mycoplasmacidal activity in the two regimens, and the maximum antimycoplasmal effects were 4.1 and 4.75log10 (CFU/mL) reduction, respectively. Furthermore, the cumulative percentage of time over a 48-h period that the drug concentration exceeds the MIC (%T > MIC) was the pharmacokinetic-pharmacodynamic index that best correlated with antimicrobial efficacy (R (2) = 0.986, compared with 0.897 for the peak level divided by the MIC and 0.953 for the area under the concentration-time curve over 48 h divided by the MIC). The estimated %T > MIC values for 0log10 (CFU/mL) reduction, 2log10 (CFU/mL) reduction and 3log10 (CFU/mL) reduction were 32.48, 45.68, and 54.36%, respectively, during 48 h treatment period of doxycycline. In conclusion, doxycycline shows excellent effectiveness and time-dependent characteristics against M. gallisepticum strain S6 in vitro. Additionally, these results will guide optimal dosing strategies of doxycycline in M. gallisepticum infection. PMID- 27199970 TI - Co-occurrence Analysis of Microbial Taxa in the Atlantic Ocean Reveals High Connectivity in the Free-Living Bacterioplankton. AB - We determined the taxonomic composition of the bacterioplankton of the epipelagic zone of the Atlantic Ocean along a latitudinal transect (51 degrees S-47 degrees N) using Illumina sequencing of the V5-V6 region of the 16S rRNA gene and inferred co-occurrence networks. Bacterioplankon community composition was distinct for Longhurstian provinces and water depth. Free-living microbial communities (between 0.22 and 3 MUm) were dominated by highly abundant and ubiquitous taxa with streamlined genomes (e.g., SAR11, SAR86, OM1, Prochlorococcus) and could clearly be separated from particle-associated communities which were dominated by Bacteroidetes, Planktomycetes, Verrucomicrobia, and Roseobacters. From a total of 369 different communities we then inferred co-occurrence networks for each size fraction and depth layer of the plankton between bacteria and between bacteria and phototrophic micro eukaryotes. The inferred networks showed a reduction of edges in the deepest layer of the photic zone. Networks comprised of free-living bacteria had a larger amount of connections per OTU when compared to the particle associated communities throughout the water column. Negative correlations accounted for roughly one third of the total edges in the free-living communities at all depths, while they decreased with depth in the particle associated communities where they amounted for roughly 10% of the total in the last part of the epipelagic zone. Co-occurrence networks of bacteria with phototrophic micro eukaryotes were not taxon-specific, and dominated by mutual exclusion (~60%). The data show a high degree of specialization to micro-environments in the water column and highlight the importance of interdependencies particularly between free-living bacteria in the upper layers of the epipelagic zone. PMID- 27199975 TI - Commentary: Agroforestry leads to shifts within the gammaproteobacterial microbiome of banana plants cultivated in Central America. PMID- 27199974 TI - Identification of a Peptide Produced by Bifidobacterium longum CECT 7210 with Antirotaviral Activity. AB - Rotavirus is one of the main causes of acute diarrhea and enteritis in infants. Currently, studies are underway to assess the use of probiotics to improve rotavirus vaccine protection. A previous work demonstrated that the probiotic strain Bifidobacterium longum subsp. infantis CECT 7210 is able to hinder rotavirus replication both in vitro and in vivo. The present study takes a systematic approach in order to identify the molecule directly involved in rotavirus inhibition. Supernatant protease digestions revealed both the proteinaceous nature of the active substance and the fact that the molecule responsible for inhibiting rotavirus replication is released to the supernatant. Following purification by cationic exchange chromatography, active fractions were obtained and the functional compound was identified as an 11-amino acid peptide (MHQPHQPLPPT, named 11-mer peptide) with a molecular mass of 1.282 KDa. The functionality of 11-mer was verified using the synthesized peptide in Wa, Ito, and VA70 rotavirus infections of both HT-29 and MA-104 cell lines. Finally, protease activity was detected in B. longum subsp. infantis CECT 7210 supernatant, which releases 11-mer peptide. A preliminary identification of the protease is also included in the study. PMID- 27199973 TI - Networks of Host Factors that Interact with NS1 Protein of Influenza A Virus. AB - Pigs are an important host of influenza A viruses due to their ability to generate reassortant viruses with pandemic potential. NS1 protein of influenza A viruses is a key virulence factor and a major antagonist of innate immune responses. It is also involved in enhancing viral mRNA translation and regulation of virus replication. Being a protein with pleiotropic functions, NS1 has a variety of cellular interaction partners. Hence, studies on swine influenza viruses (SIV) and identification of swine influenza NS1-interacting host proteins is of great interest. Here, we constructed a recombinant SIV carrying a Strep-tag in the NS1 protein and infected primary swine respiratory epithelial cells (SRECs) with this virus. The Strep-tag sequence in the NS1 protein enabled us to purify intact, the NS1 protein and its interacting protein complex specifically. We identified cellular proteins present in the purified complex by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and generated a dataset of these proteins. 445 proteins were identified by LC-MS/MS and among them 192 proteins were selected by setting up a threshold based on MS parameters. The selected proteins were analyzed by bioinformatics and were categorized as belonging to different functional groups including translation, RNA processing, cytoskeleton, innate immunity, and apoptosis. Protein interaction networks were derived using these data and the NS1 interactions with some of the specific host factors were verified by immunoprecipitation. The novel proteins and the networks revealed in our study will be the potential candidates for targeted study of the molecular interaction of NS1 with host proteins, which will provide insights into the identification of new therapeutic targets to control influenza infection and disease pathogenesis. PMID- 27199976 TI - Dietary Shifts May Trigger Dysbiosis and Mucous Stools in Giant Pandas (Ailuropoda melanoleuca). AB - Dietary shifts can result in changes to the gastrointestinal tract (GIT) microbiota, leading to negative outcomes for the host, including inflammation. Giant pandas (Ailuropoda melanoleuca) are physiologically classified as carnivores; however, they consume an herbivorous diet with dramatic seasonal dietary shifts and episodes of chronic GIT distress with symptoms including abdominal pain, loss of appetite and the excretion of mucous stools (mucoids). These episodes adversely affect the overall nutritional and health status of giant pandas. Here, we examined the fecal microbiota of two giant pandas' non mucoid and mucoid stools and compared these to samples from a previous winter season that had historically few mucoid episodes. To identify the microbiota present, we isolated and sequenced the 16S rRNA using next-generation sequencing. Mucoids occurred following a seasonal feeding switch from predominately bamboo culm (stalk) to leaves. All fecal samples displayed low diversity and were dominated by bacteria in the phyla Firmicutes and to a lesser extent, Proteobacteria. Fecal samples immediately prior to mucoid episodes had lower microbial diversity as compared to mucoids. Mucoids were mostly comprised of common mucosal-associated taxa including Streptococcus and Leuconostoc species, and exhibited increased abundance for bacteria in the family Pasteurellaceae. Taken together, these findings indicate that mucoids may represent an expulsion of the mucosal lining that is driven by changes in diet. We suggest that these occurrences serve to reset their GIT microbiota following changes in bamboo part preference, as giant pandas have retained a carnivorous GIT anatomy while shifting to an herbivorous diet. PMID- 27199977 TI - Diversity and Evolution of Type IV pili Systems in Archaea. AB - Many surface structures in archaea including various types of pili and the archaellum (archaeal flagellum) are homologous to bacterial type IV pili systems (T4P). The T4P consist of multiple proteins, often with poorly conserved sequences, complicating their identification in sequenced genomes. Here we report a comprehensive census of T4P encoded in archaeal genomes using sensitive methods for protein sequence comparison. This analysis confidently identifies as T4P components about 5000 archaeal gene products, 56% of which are currently annotated as hypothetical in public databases. Combining results of this analysis with a comprehensive comparison of genomic neighborhoods of the T4P, we present models of organization of 10 most abundant variants of archaeal T4P. In addition to the differentiation between major and minor pilins, these models include extra components, such as S-layer proteins, adhesins and other membrane and intracellular proteins. For most of these systems, dedicated major pilin families are identified including numerous stand alone major pilin genes of the PilA family. Evidence is presented that secretion ATPases of the T4P and cognate TadC proteins can interact with different pilin sets. Modular evolution of T4P results in combinatorial variability of these systems. Potential regulatory or modulating proteins for the T4P are identified including KaiC family ATPases, vWA domain containing proteins and the associated MoxR/GvpN ATPase, TFIIB homologs and multiple unrelated transcription regulators some of which are associated specific T4P. Phylogenomic analysis suggests that at least one T4P system was present in the last common ancestor of the extant archaea. Multiple cases of horizontal transfer and lineage-specific duplication of T4P loci were detected. Generally, the T4P of the archaeal TACK superphylum are more diverse and evolve notably faster than those of euryarchaea. The abundance and enormous diversity of T4P in hyperthermophilic archaea present a major enigma. Apparently, fundamental aspects of the biology of hyperthermophiles remain to be elucidated. PMID- 27199978 TI - Warming Alters Expressions of Microbial Functional Genes Important to Ecosystem Functioning. AB - Soil microbial communities play critical roles in ecosystem functioning and are likely altered by climate warming. However, so far, little is known about effects of warming on microbial functional gene expressions. Here, we applied functional gene array (GeoChip 3.0) to analyze cDNA reversely transcribed from total RNA to assess expressed functional genes in active soil microbial communities after nine years of experimental warming in a tallgrass prairie. Our results showed that warming significantly altered the community wide gene expressions. Specifically, expressed genes for degrading more recalcitrant carbon were stimulated by warming, likely linked to the plant community shift toward more C4 species under warming and to decrease the long-term soil carbon stability. In addition, warming changed expressed genes in labile C degradation and N cycling in different directions (increase and decrease), possibly reflecting the dynamics of labile C and available N pools during sampling. However, the average abundances of expressed genes in phosphorus and sulfur cycling were all increased by warming, implying a stable trend of accelerated P and S processes which might be a mechanism to sustain higher plant growth. Furthermore, the expressed gene composition was closely related to both dynamic (e.g., soil moisture) and stable environmental attributes (e.g., C4 leaf C or N content), indicating that RNA analyses could also capture certain stable trends in the long-term treatment. Overall, this study revealed the importance of elucidating functional gene expressions of soil microbial community in enhancing our understanding of ecosystem responses to warming. PMID- 27199980 TI - Erratum: Defining Mononuclear Phagocyte Subset Homology across Several Distant Warm-Blooded Vertebrates through Comparative Transcriptomics. AB - [This corrects the article on p. 299 in vol. 6, PMID: 26150816.]. PMID- 27199979 TI - The Autoimmune Ecology. AB - Autoimmune diseases (ADs) represent a heterogeneous group of disorders that affect specific target organs or multiple organ systems. These conditions share common immunopathogenic mechanisms (i.e., the autoimmune tautology), which explain the clinical similarities they have among them as well as their familial clustering (i.e., coaggregation). As part of the autoimmune tautology, the influence of environmental exposure on the risk of developing ADs is paramount (i.e., the autoimmune ecology). In fact, environment, more than genetics, shapes immune system. Autoimmune ecology is akin to exposome, that is all the exposures internal and external - across the lifespan, interacting with hereditary factors (both genetics and epigenetics) to favor or protect against autoimmunity and its outcomes. Herein, we provide an overview of the autoimmune ecology, focusing on the immune response to environmental agents in general, and microbiota, cigarette smoking, alcohol and coffee consumption, socioeconomic status (SES), gender and sex hormones, vitamin D, organic solvents, and vaccines in particular. Inclusion of the autoimmune ecology in disease etiology and health will improve the way personalized medicine is currently conceived and applied. PMID- 27199981 TI - Paradoxical Roles of the Neutrophil in Sepsis: Protective and Deleterious. AB - Sepsis, an overwhelming inflammatory response syndrome secondary to infection, is one of the costliest and deadliest medical conditions worldwide. Neutrophils are classically considered to be essential players in the host defense against invading pathogens. However, several investigations have shown that impairment of neutrophil migration to the site of infection, also referred to as neutrophil paralysis, occurs during severe sepsis, resulting in an inability of the host to contain and eliminate the infection. On the other hand, the neutrophil antibacterial arsenal contributes to tissue damage and the development of organ dysfunction during sepsis. In this review, we provide an overview of the main events in which neutrophils play a beneficial or deleterious role in the outcome of sepsis. PMID- 27199983 TI - Alternative Pathway Dysregulation and the Conundrum of Complement Activation by IgG4 Immune Complexes in Membranous Nephropathy. AB - Membranous nephropathy (MN), a major cause of nephrotic syndrome, is a non inflammatory immune kidney disease mediated by IgG antibodies that form glomerular subepithelial immune complexes. In primary MN, autoantibodies target proteins expressed on the podocyte surface, often phospholipase A2 receptor (PLA2R1). Pathology is driven by complement activation, leading to podocyte injury and proteinuria. This article overviews the mechanisms of complement activation and regulation in MN, addressing the paradox that anti-PLA2R1 and other antibodies causing primary MN are predominantly (but not exclusively) IgG4, an IgG subclass that does not fix complement. Besides immune complexes, alterations of the glomerular basement membrane (GBM) in MN may lead to impaired regulation of the alternative pathway (AP). The AP amplifies complement activation on surfaces insufficiently protected by complement regulatory proteins. Whereas podocytes are protected by cell-bound regulators, the GBM must recruit plasma factor H, which inhibits the AP on host surfaces carrying certain polyanions, such as heparan sulfate (HS) chains. Because HS chains present in the normal GBM are lost in MN, we posit that the local complement regulation by factor H may be impaired as a result. Thus, the loss of GBM HS in MN creates a micro-environment that promotes local amplification of complement activation, which in turn may be initiated via the classical or lectin pathways by subsets of IgG in immune complexes. A detailed understanding of the mechanisms of complement activation and dysregulation in MN is important for designing more effective therapies. PMID- 27199982 TI - Role of Redox Status in Development of Glioblastoma. AB - Glioblastoma multiforme (GBM) is a highly aggressive neoplasia, prognosis remains dismal, and current therapy is mostly palliative. There are no known risk factors associated with gliomagenesis; however, it is well established that chronic inflammation in brain tissue induces oxidative stress in astrocytes and microglia. High quantities of reactive species of oxygen into the cells can react with several macromolecules, including chromosomal and mitochondrial DNA, leading to damage and malfunction of DNA repair enzymes. These changes bring genetic instability and abnormal metabolic processes, favoring oxidative environment and increase rate of cell proliferation. In GBM, a high metabolic rate and increased basal levels of reactive oxygen species play an important role as chemical mediators in the regulation of signal transduction, protecting malignant cells from apoptosis, thus creating an immunosuppressive environment. New redox therapeutics could reduce oxidative stress preventing cellular damage and high mutation rate accompanied by chromosomal instability, reducing the immunosuppressive environment. In addition, therapies directed to modulate redox rate reduce resistance and moderate the high rate of cell proliferation, favoring apoptosis of tumoral cells. This review describes the redox status in GBM, and how this imbalance could promote gliomagenesis through genomic and mitochondrial DNA damage, inducing the pro-oxidant and proinflammatory environment involved in tumor cell proliferation, resistance, and immune escape. In addition, some therapeutic agents that modulate redox status and might be advantageous in therapy against GBM are described. PMID- 27199984 TI - Extracellular HSPs: The Complicated Roles of Extracellular HSPs in Immunity. AB - Extracellular heat-shock proteins (HSPs) interact with the immune system in a very complex manner. Many such HSPs exert powerful effects on the immune response, playing both stimulatory and regulatory roles. However, the influence of the HSPs on immunity appears to be positive or negative in nature - rarely neutral. Thus, the HSPs can act as dominant antigens and can comprise key components of antitumor vaccines. They can also function as powerful immunoregulatory agents and, as such, are employed to treat inflammatory diseases or to extend the lifespan of tissue transplants. Small modifications in the cellular milieu have been shown to flip the allegiances of HSPs from immunoregulatory agents toward a potent inflammatory alignment. These mutable properties of HSPs may be related to the ability of these proteins to interact with multiple receptors often with mutually confounding properties in immune cells. Therefore, understanding the complex immune properties of HSPs may help us to harness their potential in treatment of a range of conditions. PMID- 27199987 TI - A Multi-Component Prime-Boost Vaccination Regimen with a Consensus MOMP Antigen Enhances Chlamydia trachomatis Clearance. AB - BACKGROUND: A vaccine for Chlamydia trachomatis is of urgent medical need. We explored bioinformatic approaches to generate an immunogen against C. trachomatis that would induce cross-serovar T-cell responses as (i) CD4(+) T cells have been shown in animal models and human studies to be important in chlamydial protection and (ii) antibody responses may be restrictive and serovar specific. METHODS: A consensus antigen based on over 1,500 major outer membrane protein (MOMP) sequences provided high epitope coverage against the most prevalent C. trachomatis strains in silico. Having designed the T-cell immunogen, we assessed it for immunogenicity in prime-boost regimens. This consensus MOMP transgene was delivered using plasmid DNA, Human Adenovirus 5 (HuAd5) or modified vaccinia Ankara (MVA) vectors with or without MF59((r)) adjuvanted recombinant MOMP protein. RESULTS: Different regimens induced distinct immune profiles. The DNA HuAd5-MVA-Protein vaccine regimen induced a cellular response with a Th1-biased serum antibody response, alongside high serum and vaginal MOMP-specific antibodies. This regimen significantly enhanced clearance against intravaginal C. trachomatis serovar D infection in both BALB/c and B6C3F1 mouse strains. This enhanced clearance was shown to be CD4(+) T-cell dependent. Future studies will need to confirm the specificity and precise mechanisms of protection. CONCLUSION: A C. trachomatis vaccine needs to induce a robust cellular response with broad cross-serovar coverage and a heterologous prime-boost regimen may be an approach to achieve this. PMID- 27199986 TI - Post-transcriptional Regulation of Immunological Responses through Riboclustering. AB - Immunological programing of immune cells varies in response to changing environmental signals. This process is facilitated by modifiers that regulate the translational fate of mRNAs encoding various immune mediators, including cytokines and chemokines, which in turn determine the rapid activation, tolerance, and plasticity of the immune system. RNA-binding proteins (RBPs) recruited by the specific sequence elements in mRNA transcripts are one such modifiers. These RBPs form RBP-RNA complexes known as "riboclusters." These riboclusters serve as RNA sorting machinery, where depending upon the composition of the ribocluster, translation, degradation, or storage of mRNA is controlled. Recent findings suggest that this regulation of mRNA homeostasis is critical for controlling the immune response. Here, we present the current knowledge of the ribocluster-mediated post-transcriptional regulation of immune mediators and highlight recent findings regarding their implications for the pathogenesis of acute or chronic inflammatory diseases. PMID- 27199989 TI - Pattern of Infectious Morbidity in HIV-Exposed Uninfected Infants and Children. AB - BACKGROUND: Almost 30% of children in Southern Africa are HIV exposed but uninfected (HEU) and experience exposures that could increase vulnerability to infectious diseases compared to HIV unexposed (HU) children. The mechanisms of HEU infant vulnerability remain ill-defined. This review seeks to appraise the existing clinical evidence of the pattern of HEU infant infectious morbidity to aid understanding of the potential mechanism of susceptibility. METHODS: A systematic search was conducted of scientific literature databases and conference proceedings up to December 2015 for studies comparing adequately defined HEU (in whom HIV-infection had been excluded through age-appropriate testing) and HU infants for all-cause mortality, all-cause hospitalization, or an infection related morbidity. The systematic review was complemented by a narrative review of additional studies detailing the pattern of infectious morbidity experienced by HEU children without comparison to HU children or without conclusive exclusion of HIV-infection in HIV-exposed infants. RESULTS: Only 3 of 22 eligible identified studies were designed to primarily compare HEU and HU infants for infectious morbidity. Fourteen were conducted prior to 2009 in the context of limited antiretroviral interventions. Three patterns emerge: (1) causes of morbidity and mortality in HEU infants are consistent with the common causes of childhood morbidity and mortality (pneumonia, diarrheal disease, and bacterial sepsis) but occur with greater severity in HEU infants resulting in higher mortality, more frequent hospitalization, and more severe manifestations of disease; (2) the greatest relative difference between HEU and HU infants in morbidity and mortality occurs beyond the neonatal period, during mid-infancy, having waned by the second year of life; and (3) HEU infants are at greater risk than HU infants for invasive streptococcal infections specifically Group B Streptococcus and Streptococcus pneumonia. CONCLUSION: To definitively understand HEU infant infectious morbidity risk, substantially larger prospective studies with appropriate HU infant comparison groups are necessary. HEU children would benefit from collaboration among researchers to achieve the quality of evidence required to improve HEU infant outcomes globally. HEU infant health and well being, beyond avoiding HIV-infection, deserves a more prominent position in the local and international HIV research agendas. PMID- 27199985 TI - Resolution of Inflammation: What Controls Its Onset? AB - An effective resolution program may be able to prevent the progression from non resolving acute inflammation to persistent chronic inflammation. It has now become evident that coordinated resolution programs initiate shortly after inflammatory responses begin. In this context, several mechanisms provide the fine-tuning of inflammation and create a favorable environment for the resolution phase to take place and for homeostasis to return. In this review, we focus on the events required for an effective transition from the proinflammatory phase to the onset and establishment of resolution. We suggest that several mediators that promote the inflammatory phase of inflammation can simultaneously initiate a program for active resolution. Indeed, several events enact a decrease in the local chemokine concentration, a reduction which is essential to inhibit further infiltration of neutrophils into the tissue. Interestingly, although neutrophils are cells that characteristically participate in the active phase of inflammation, they also contribute to the onset of resolution. Further understanding of the molecular mechanisms that initiate resolution may be instrumental to develop pro-resolution strategies to treat complex chronic inflammatory diseases, in humans. The efforts to develop strategies based on resolution of inflammation have shaped a new area of pharmacology referred to as "resolution pharmacology." PMID- 27199988 TI - STAT3, a Key Parameter of Cytokine-Driven Tissue Protection during Sterile Inflammation - the Case of Experimental Acetaminophen (Paracetamol)-Induced Liver Damage. AB - Acetaminophen (APAP, N-acetyl-p-aminophenol, or paracetamol) overdosing is a prevalent cause of acute liver injury. While clinical disease is initiated by overt parenchymal hepatocyte necrosis in response to the analgetic, course of intoxication is substantially influenced by associated activation of innate immunity. This process is supposed to be set in motion by release of danger associated molecular patterns (DAMPs) from dying hepatocytes and is accompanied by an inflammatory cytokine response. Murine models of APAP-induced liver injury emphasize the complex role that DAMPs and cytokines play in promoting either hepatic pathogenesis or resolution and recovery from intoxication. Whereas the function of key inflammatory cytokines is controversially discussed, a subclass of specific cytokines capable of efficiently activating the hepatocyte signal transducer and activator of transcription (STAT)-3 pathway stands out as being consistently protective in murine models of APAP intoxication. Those include foremost interleukin (IL)-6, IL-11, IL-13, and IL-22. Above all, activation of STAT3 under the influence of these cytokines has the capability to drive hepatocyte compensatory proliferation, a key principle of the regenerating liver. Herein, the role of these specific cytokines during experimental APAP-induced liver injury is highlighted and discussed in a broader perspective. In hard-to treat or at-risk patients, standard therapy may fail and APAP intoxication can proceed toward a fatal condition. Focused administration of recombinant STAT3 activating cytokines may evolve as novel therapeutic approach under those ill fated conditions. PMID- 27199991 TI - Editorial: Dendritic Cell and Macrophage Nomenclature and Classification. PMID- 27199990 TI - Licensed and Unlicensed NK Cells: Differential Roles in Cancer and Viral Control. AB - Natural killer (NK) cells are known for their well characterized ability to control viral infections and eliminate tumor cells. Through their repertoire of activating and inhibitory receptors, NK cells are able to survey different potential target cells for various surface markers, such as MHC-I - which signals to the NK cell that the target is healthy - as well as stress ligands or viral proteins, which alert the NK cell to the aberrant state of the target and initiate a response. According to the "licensing" hypothesis, interactions between self-specific MHC-I receptors - Ly49 in mice and KIR in humans - and self MHC-I molecules during NK cell development is crucial for NK cell functionality. However, there also exists a large proportion of NK cells in mice and humans, which lack self-specific MHC-I receptors and are consequentially "unlicensed." While the licensed NK cell subset plays a major role in the control of MHC-I deficient tumors, this review will go on to highlight the important role of the unlicensed NK cell subset in the control of MHC-I-expressing tumors, as well as in viral control. Unlike the licensed NK cells, unlicensed NK cells seem to benefit from the lack of self-specific inhibitory receptors, which could otherwise be exploited by some aberrant cells for immunoevasion by upregulating the expression of ligands or mimic ligands for these receptors. PMID- 27199992 TI - Allosteric Modulation of Chemoattractant Receptors. AB - Chemoattractants control selective leukocyte homing via interactions with a dedicated family of related G protein-coupled receptor (GPCR). Emerging evidence indicates that the signaling activity of these receptors, as for other GPCR, is influenced by allosteric modulators, which interact with the receptor in a binding site distinct from the binding site of the agonist and modulate the receptor signaling activity in response to the orthosteric ligand. Allosteric modulators have a number of potential advantages over orthosteric agonists/antagonists as therapeutic agents and offer unprecedented opportunities to identify extremely selective drug leads. Here, we resume evidence of allosterism in the context of chemoattractant receptors, discussing in particular its functional impact on functional selectivity and probe/concentration dependence of orthosteric ligands activities. PMID- 27199993 TI - Heat Shock Protein-Peptide and HSP-Based Immunotherapies for the Treatment of Cancer. AB - Intracellular residing heat shock proteins (HSPs) with a molecular weight of approximately 70 and 90 kDa function as molecular chaperones that assist folding/unfolding and transport of proteins across membranes and prevent protein aggregation after environmental stress. In contrast to normal cells, tumor cells have higher cytosolic heat shock protein 70 and Hsp90 levels, which contribute to tumor cell propagation, metastasis, and protection against apoptosis. In addition to their intracellular chaperoning functions, extracellular localized and membrane-bound HSPs have been found to play key roles in eliciting antitumor immune responses by acting as carriers for tumor-derived immunogenic peptides, as adjuvants for antigen presentation, or as targets for the innate immune system. The interaction of HSP-peptide complexes or peptide-free HSPs with receptors on antigen-presenting cells promotes the maturation of dendritic cells, results in an upregulation of major histocompatibility complex class I and class II molecules, induces secretion of pro- and anti-inflammatory cytokines, chemokines, and immune modulatory nitric oxides, and thus integrates adaptive and innate immune phenomena. Herein, we aim to recapitulate the history and current status of HSP-based immunotherapies and vaccination strategies in the treatment of cancer. PMID- 27199994 TI - Regulation of T Cell Differentiation and Function by EZH2. AB - The enhancer of zeste homolog 2 (EZH2), one of the polycomb-group proteins, is the catalytic subunit of Polycomb-repressive complex 2 (PRC2) and induces the trimethylation of the histone H3 lysine 27 (H3K27me3) promoting epigenetic gene silencing. EZH2 contains a SET domain promoting the methyltransferase activity, while the three other protein components of PRC2, namely EED, SUZ12, and RpAp46/48, induce compaction of the chromatin permitting EZH2 enzymatic activity. Numerous studies highlight the role of this evolutionary conserved protein as a master regulator of differentiation in humans involved in the repression of the homeotic gene and the inactivation of X-chromosome. Through its effects in the epigenetic regulation of critical genes, EZH2 has been strongly linked to cell cycle progression, stem cell pluripotency, and cancer biology, being currently at the cutting edge of research. Most recently, EZH2 has been associated with hematopoietic stem cell proliferation and differentiation, thymopoiesis and lymphopoiesis. Several studies have evaluated the role of EZH2 in the regulation of T cell differentiation and plasticity as well as its implications in the development of autoimmune diseases and graft-versus-host disease (GVHD). The aim of this review is to summarize the current knowledge regarding the role of EZH2 in the regulation of the differentiation and function of T cells focusing on possible applications in various immune-mediated conditions, including autoimmune disorders and GVHD. PMID- 27199996 TI - Host Lipid Bodies as Platforms for Intracellular Survival of Protozoan Parasites. AB - Pathogens induce several changes in the host cell signaling and trafficking mechanisms in order to evade and manipulate the immune response. One prominent pathogen-mediated change is the formation of lipid-rich organelles, termed lipid bodies (LBs) or lipid droplets, in the host cell cytoplasm. Protozoan parasites, which contribute expressively to the burden of infectious diseases worldwide, are able to induce LB genesis in non-immune and immune cells, mainly macrophages, key players in the initial resistance to the infection. Under host-parasite interaction, LBs not only accumulate in the host cytoplasm but also relocate around and move into parasitophorous vacuoles. There is increasing evidence that protozoan parasites may target host-derived LBs either for gaining nutrients or for escaping the host immune response. Newly formed, parasite-induced LBs may serve as lipid sources for parasite growth and also produce inflammatory mediators that potentially act in the host immune response deactivation. In this mini review, we summarize current knowledge on the formation and role of host LBs as sites exploited by intracellular protozoan parasites as a strategy to maintain their own survival. PMID- 27199995 TI - The Potential of HLA-G-Bearing Extracellular Vesicles as a Future Element in HLA G Immune Biology. AB - The HLA-G molecule is a member of the non-classical HLA class I family. Its surface expression is physiologically restricted to the maternal-fetal interface and to immune privileged adult tissues. Despite the restricted tissue expression, HLA-G is detectable in body fluids as secreted soluble molecules. A unique feature of HLA-G is the structural diversity as surface expressed and as secreted molecules. Secreted HLA-G can be found in various body fluids either as free soluble HLA-G or as part of extracellular vesicles (EVs), which are composed of various antigens/ligands/receptors, bioactive lipids, cytokines, growth factors, and genetic information, such as mRNA and microRNA. Functionally, HLA-G and its secreted forms are considered to play a crucial role in the network of immune regulatory tolerance mechanisms, preferentially interacting with the cognate inhibitory receptors LILRB1 and LILRB2. The HLA-G mediated tolerance is described in processes of pregnancy, inflammation, and cancer. However, almost all functional and clinical implications of HLA-G in vivo and in vitro have been established based on simple single ligand/receptor interactions at the cell surface, whereas HLA-G-bearing EVs were in minor research focus. Indeed, cytotrophoblast cells, mesenchymal stem cells, and cancer cells were recently described to secrete HLA-G-bearing EVs, displaying immunosuppressive effects and modulating the tumor microenvironment. However, numerous functional and clinical open questions persist. Here, we (i) introduce basic aspects of EVs biology, (ii) summarize the functional knowledge, clinical implications and open questions of HLA-G-bearing EVs, and (iii) discuss HLA-G-bearing EVs as a future element in HLA G biology. PMID- 27199997 TI - Analyses of Methylomes Derived from Meso-American Common Bean (Phaseolus vulgaris L.) Using MeDIP-Seq and Whole Genome Sodium Bisulfite-Sequencing. AB - Common bean (Phaseolus vulgaris L.) is economically important for its high protein, fiber, and micronutrient contents, with a relatively small genome size of ~587 Mb. Common bean is genetically diverse with two major gene pools, Meso American and Andean. The phenotypic variability within common bean is partly attributed to the genetic diversity and epigenetic changes that are largely influenced by environmental factors. It is well established that an important epigenetic regulator of gene expression is DNA methylation. Here, we present results generated from two high-throughput sequencing technologies, methylated DNA immunoprecipitation-sequencing (MeDIP-seq) and whole genome bisulfite sequencing (BS-Seq). Our analyses revealed that this Meso-American common bean displays similar methylation patterns as other previously published plant methylomes, with CG ~50%, CHG ~30%, and CHH ~2.7% methylation, however, these differ from the common bean reference methylome of Andean origin. We identified higher CG methylation levels in both promoter and genic regions than CHG and CHH contexts. Moreover, we found relatively higher CG methylation levels in genes than in promoters. Conversely, the CHG and CHH methylation levels were highest in promoters than in genes. This is the first genome-wide DNA methylation profiling study in a Meso-American common bean cultivar ("Sierra") using NGS approaches. Our long-term goal is to generate genome-wide epigenomic maps in common bean focusing on chromatin accessibility, histone modifications, and DNA methylation. PMID- 27200000 TI - Yes, We Have an Inflation of Reviews: But of the Wrong Kind! PMID- 27199998 TI - Emerging Genomic Tools for Legume Breeding: Current Status and Future Prospects. AB - Legumes play a vital role in ensuring global nutritional food security and improving soil quality through nitrogen fixation. Accelerated higher genetic gains is required to meet the demand of ever increasing global population. In recent years, speedy developments have been witnessed in legume genomics due to advancements in next-generation sequencing (NGS) and high-throughput genotyping technologies. Reference genome sequences for many legume crops have been reported in the last 5 years. The availability of the draft genome sequences and re sequencing of elite genotypes for several important legume crops have made it possible to identify structural variations at large scale. Availability of large scale genomic resources and low-cost and high-throughput genotyping technologies are enhancing the efficiency and resolution of genetic mapping and marker-trait association studies. Most importantly, deployment of molecular breeding approaches has resulted in development of improved lines in some legume crops such as chickpea and groundnut. In order to support genomics-driven crop improvement at a fast pace, the deployment of breeder-friendly genomics and decision support tools seems appear to be critical in breeding programs in developing countries. This review provides an overview of emerging genomics and informatics tools/approaches that will be the key driving force for accelerating genomics-assisted breeding and ultimately ensuring nutritional and food security in developing countries. PMID- 27199999 TI - Hydrogen Peroxide, Signaling in Disguise during Metal Phytotoxicity. AB - Plants exposed to excess metals are challenged by an increased generation of reactive oxygen species (ROS) such as superoxide ([Formula: see text]), hydrogen peroxide (H2O2) and the hydroxyl radical ((*)OH). The mechanisms underlying this oxidative challenge are often dependent on metal-specific properties and might play a role in stress perception, signaling and acclimation. Although ROS were initially considered as toxic compounds causing damage to various cellular structures, their role as signaling molecules became a topic of intense research over the last decade. Hydrogen peroxide in particular is important in signaling because of its relatively low toxicity, long lifespan and its ability to cross cellular membranes. The delicate balance between its production and scavenging by a plethora of enzymatic and metabolic antioxidants is crucial in the onset of diverse signaling cascades that finally lead to plant acclimation to metal stress. In this review, our current knowledge on the dual role of ROS in metal exposed plants is presented. Evidence for a relationship between H2O2 and plant metal tolerance is provided. Furthermore, emphasis is put on recent advances in understanding cellular damage and downstream signaling responses as a result of metal-induced H2O2 production. Finally, special attention is paid to the interaction between H2O2 and other signaling components such as transcription factors, mitogen-activated protein kinases, phytohormones and regulating systems (e.g. microRNAs). These responses potentially underlie metal-induced senescence in plants. Elucidating the signaling network activated during metal stress is a pivotal step to make progress in applied technologies like phytoremediation of polluted soils. PMID- 27200001 TI - Two Poplar-Associated Bacterial Isolates Induce Additive Favorable Responses in a Constructed Plant-Microbiome System. AB - The biological function of the plant-microbiome system is the result of contributions from the host plant and microbiome members. The Populus root microbiome is a diverse community that has high abundance of beta- and gamma Proteobacteria, both classes which include multiple plant-growth promoting representatives. To understand the contribution of individual microbiome members in a community, we studied the function of a simplified community consisting of Pseudomonas and Burkholderia bacterial strains isolated from Populus hosts and inoculated on axenic Populus cutting in controlled laboratory conditions. Both strains increased lateral root formation and root hair production in Arabidopsis plate assays and are predicted to encode for different functions related to growth and plant growth promotion in Populus hosts. Inoculation individually, with either bacterial isolate, increased root growth relative to uninoculated controls, and while root area was increased in mixed inoculation, the interaction term was insignificant indicating additive effects of root phenotype. Complementary data including photosynthetic efficiency, whole-transcriptome gene expression and GC-MS metabolite expression data in individual and mixed inoculated treatments indicate that the effects of these bacterial strains are unique and additive. These results suggest that the function of a microbiome community may be predicted from the additive functions of the individual members. PMID- 27200002 TI - Monoterpenol Oxidative Metabolism: Role in Plant Adaptation and Potential Applications. AB - Plants use monoterpenols as precursors for the production of functionally and structurally diverse molecules, which are key players in interactions with other organisms such as pollinators, flower visitors, herbivores, fungal, or microbial pathogens. For humans, many of these monoterpenol derivatives are economically important because of their pharmaceutical, nutraceutical, flavor, or fragrance applications. The biosynthesis of these derivatives is to a large extent catalyzed by enzymes from the cytochrome P450 superfamily. Here we review the knowledge on monoterpenol oxidative metabolism in plants with special focus on recent elucidations of oxidation steps leading to diverse linalool and geraniol derivatives. We evaluate the common features between oxidation pathways of these two monoterpenols, such as involvement of the CYP76 family, and highlight the differences. Finally, we discuss the missing steps and other open questions in the biosynthesis of oxygenated monoterpenol derivatives. PMID- 27200003 TI - Calcium and Potassium Supplementation Enhanced Growth, Osmolyte Secondary Metabolite Production, and Enzymatic Antioxidant Machinery in Cadmium-Exposed Chickpea (Cicer arietinum L.). AB - This work examined the role of exogenously applied calcium (Ca; 50 mM) and potassium (K; 10 mM) (alone and in combination) in alleviating the negative effects of cadmium (Cd; 200 MUM) on growth, biochemical attributes, secondary metabolites and yield of chickpea (Cicer arietinum L.). Cd stress significantly decreased the length and weight (fresh and dry) of shoot and root and yield attributes in terms of number of pods and seed yield (vs. control). Exhibition of decreases in chlorophyll (Chl) a, Chl b, and total Chl was also observed with Cd exposure when compared to control. However, Cd-exposure led to an increase in the content of carotenoids. In contrast, the exogenous application of Ca and K individually as well as in combination minimized the extent of Cd-impact on previous traits. C. arietinum seedlings subjected to Cd treatment exhibited increased contents of organic solute (proline, Pro) and total protein; whereas, Ca and K-supplementation further enhanced the Pro and total protein content. Additionally, compared to control, Cd-exposure also caused elevation in the contents of oxidative stress markers (hydrogen peroxidase, H2O2; malondialdehyde, MDA) and in the activity of antioxidant defense enzymes (superoxide dismutase, SOD; catalase, CAT; ascorbate peroxidase, APX; glutathione reductase, GR). Ca, K, and Ca + K supplementation caused further enhancements in the activity of these enzymes but significantly decreased contents of H2O2 and MDA, also that of Cd accumulation in shoot and root. The contents of total phenol, flavonoid and mineral elements (S, Mn, Mg, Ca and K) that were also suppressed in Cd stressed plants in both shoot and root were restored to appreciable levels with Ca- and K supplementation. However, the combination of Ca + K supplementation was more effective in bringing the positive response as compared to individual effect of Ca and K on Cd-exposed C. arietinum. Overall, this investigation suggests that application of Ca and/or K can efficiently minimize Cd-toxicity and eventually improve health and yield in C. arietinum by the cumulative outcome of the enhanced contents of organic solute, secondary metabolites, mineral elements, and activity of antioxidant defense enzymes. PMID- 27200004 TI - Soybean Roots Grown under Heat Stress Show Global Changes in Their Transcriptional and Proteomic Profiles. AB - Heat stress is likely to be a key factor in the negative impact of climate change on crop production. Heat stress significantly influences the functions of roots, which provide support, water, and nutrients to other plant organs. Likewise, roots play an important role in the establishment of symbiotic associations with different microorganisms. Despite the physiological relevance of roots, few studies have examined their response to heat stress. In this study, we performed genome-wide transcriptomic and proteomic analyses on isolated root hairs, which are a single, epidermal cell type, and compared their response to stripped roots. On average, we identified 1849 and 3091 genes differentially regulated in root hairs and stripped roots, respectively, in response to heat stress. Our gene regulatory module analysis identified 10 key modules that might control the majority of the transcriptional response to heat stress. We also conducted proteomic analysis on membrane fractions isolated from root hairs and compared these responses to stripped roots. These experiments identified a variety of proteins whose expression changed within 3 h of application of heat stress. Most of these proteins were predicted to play a significant role in thermo-tolerance, as well as in chromatin remodeling and post-transcriptional regulation. The data presented represent an in-depth analysis of the heat stress response of a single cell type in soybean. PMID- 27200005 TI - Transcriptional Profiles of Drought-Related Genes in Modulating Metabolic Processes and Antioxidant Defenses in Lolium multiflorum. AB - Drought is a major environmental stress that limits growth and development of cool-season annual grasses. Drought transcriptional profiles of resistant and susceptible lines were studied to understand the molecular mechanisms of drought tolerance in annual ryegrass (Lolium multiflorum L.). A total of 4718 genes exhibited significantly differential expression in two L. multiflorum lines. Additionally, up-regulated genes associated with drought response in the resistant lines were compared with susceptible lines. Gene ontology enrichment and pathway analyses revealed that genes partially encoding drought-responsive proteins as key regulators were significantly involved in carbon metabolism, lipid metabolism, and signal transduction. Comparable gene expression was used to identify the genes that contribute to the high drought tolerance in resistant lines of annual ryegrass. Moreover, we proposed the hypothesis that short-term drought have a beneficial effect on oxidation stress, which may be ascribed to a direct effect on the drought tolerance of annual ryegrass. Evidence suggests that some of the genes encoding antioxidants (HPTs, GGT, AP, 6-PGD, and G6PDH) function as antioxidant in lipid metabolism and signal transduction pathways, which have indispensable and promoting roles in drought resistance. This study provides the first transcriptome data on the induction of drought-related gene expression in annual ryegrass, especially via modulation of metabolic homeostasis, signal transduction, and antioxidant defenses to improve drought tolerance response to short-term drought stress. PMID- 27200007 TI - Nitric Oxide Alleviates Salt Stress Inhibited Photosynthetic Performance by Interacting with Sulfur Assimilation in Mustard. AB - The role of nitric oxide (NO) and sulfur (S) on stomatal responses and photosynthetic performance was studied in mustard (Brassica juncea L.) in presence or absence of salt stress. The combined application of 100 MUM NO (as sodium nitroprusside) and 200 mg S kg(-1) soil (S) more prominently influenced stomatal behavior, photosynthetic and growth performance both in the absence and presence of salt stress. The chloroplasts from salt-stressed plants had disorganized chloroplast thylakoids, but combined application of NO and S resulted in well-developed chloroplast thylakoids and properly stacked grana. The leaves from plants receiving NO plus S exhibited lower superoxide ion accumulation under salt stress than the plants receiving NO or S. These plants also exhibited increased activity of ATP-sulfurylase (ATPS), catalase (CAT), ascorbate peroxidase (APX) and glutathione reductase (GR) and optimized NO generation that helped in minimizing oxidative stress. The enhanced S assimilation of these plants receiving NO plus S resulted in increased production of cysteine (Cys) and reduced glutathione (GSH). These findings indicated that NO influenced photosynthesis under salt stress by regulating oxidative stress and its effects on S-assimilation, an antioxidant system and NO generation. The results suggest that NO improves photosynthetic performance of plants grown under salt stress more effectively when plants received S. PMID- 27200006 TI - Identification and Overexpression of a Knotted1-Like Transcription Factor in Switchgrass (Panicum virgatum L.) for Lignocellulosic Feedstock Improvement. AB - High biomass production and wide adaptation has made switchgrass (Panicum virgatum L.) an important candidate lignocellulosic bioenergy crop. One major limitation of this and other lignocellulosic feedstocks is the recalcitrance of complex carbohydrates to hydrolysis for conversion to biofuels. Lignin is the major contributor to recalcitrance as it limits the accessibility of cell wall carbohydrates to enzymatic breakdown into fermentable sugars. Therefore, genetic manipulation of the lignin biosynthesis pathway is one strategy to reduce recalcitrance. Here, we identified a switchgrass Knotted1 transcription factor, PvKN1, with the aim of genetically engineering switchgrass for reduced biomass recalcitrance for biofuel production. Gene expression of the endogenous PvKN1 gene was observed to be highest in young inflorescences and stems. Ectopic overexpression of PvKN1 in switchgrass altered growth, especially in early developmental stages. Transgenic lines had reduced expression of most lignin biosynthetic genes accompanied by a reduction in lignin content suggesting the involvement of PvKN1 in the broad regulation of the lignin biosynthesis pathway. Moreover, the reduced expression of the Gibberellin 20-oxidase (GA20ox) gene in tandem with the increased expression of Gibberellin 2-oxidase (GA2ox) genes in transgenic PvKN1 lines suggest that PvKN1 may exert regulatory effects via modulation of GA signaling. Furthermore, overexpression of PvKN1 altered the expression of cellulose and hemicellulose biosynthetic genes and increased sugar release efficiency in transgenic lines. Our results demonstrated that switchgrass PvKN1 is a putative ortholog of maize KN1 that is linked to plant lignification and cell wall and development traits as a major regulatory gene. Therefore, targeted overexpression of PvKN1 in bioenergy feedstocks may provide one feasible strategy for reducing biomass recalcitrance and simultaneously improving plant growth characteristics. PMID- 27200008 TI - Evaluation of Sorghum [Sorghum bicolor (L.)] Reference Genes in Various Tissues and under Abiotic Stress Conditions for Quantitative Real-Time PCR Data Normalization. AB - Accurate and reliable gene expression data from qPCR depends on stable reference gene expression for potential gene functional analyses. In this study, 15 reference genes were selected and analyzed in various sample sets including abiotic stress treatments (salt, cold, water stress, heat, and abscisic acid) and tissues (leaves, roots, seedlings, panicle, and mature seeds). Statistical tools, including geNorm, NormFinder and RefFinder, were utilized to assess the suitability of reference genes based on their stability rankings for various sample groups. For abiotic stress, PP2A and CYP were identified as the most stable genes. In contrast, EIF4alpha was the most stable in the tissue sample set, followed by PP2A; PP2A was the most stable in all the sample set, followed by EIF4alpha. GAPDH, and UBC1 were the least stably expressed in the tissue and all the sample sets. These results also indicated that the use of two candidate reference genes would be sufficient for the optimization of normalization studies. To further verify the suitability of these genes for use as reference genes, SbHSF5 and SbHSF13 gene expression levels were normalized using the most and least stable sorghum reference genes in root and water stressed-leaf tissues of five sorghum varieties. This is the first systematic study of the selection of the most stable reference genes for qPCR-related assays in Sorghum bicolor that will potentially benefit future gene expression studies in sorghum and other closely related species. PMID- 27200010 TI - The Rice Eukaryotic Translation Initiation Factor 3 Subunit f (OseIF3f) Is Involved in Microgametogenesis. AB - Microgametogenesis is the post-meiotic pollen developmental phase when unicellular microspores develop into mature tricellular pollen. In rice, microgametogenesis can influence grain yields to a great degree because pollen abortion occurs more easily during microgametogenesis than during other stages of pollen development. However, our knowledge of the genes involved in microgametogenesis in rice remains limited. Due to the dependence of pollen development on the regulatory mechanisms of protein expression, we identified the encoding gene of the eukaryotic translation initiation factor 3, subunit f in Oryza sativa (OseIF3f). Immunoprecipitation combined with mass spectrometry confirmed that OseIF3f was a subunit of rice eIF3, which consisted of at least 12 subunits including eIF3a, eIF3b, eIF3c, eIF3d, eIF3e, eIF3f, eIF3g, eIF3h, eIF3i, eIF3k, eIF3l, and eIF3m. OseIF3f showed high mRNA levels in immature florets and is highly abundant in developing anthers. Subcellular localization analysis showed that OseIF3f was localized to the cytosol and the endoplasmic reticulum in rice root cells. We further analyzed the biological function of OseIF3f using the double-stranded RNA-mediated interference (RNAi) approach. The OseIF3f-RNAi lines grew normally at the vegetative stage but displayed a large reduction in seed production and pollen viability, which is associated with the down-regulation of OseIF3f. Further cytological observations of pollen development revealed that the OseIF3f-RNAi lines showed no obvious abnormalities at the male meiotic stage and the unicellular microspore stage. However, compared to the wild-type, OseIF3f RNAi lines contained a higher percentage of arrested unicellular pollen at the bicellular stage and a higher percentage of arrested unicellular and bicellular pollen, and aborted pollen at the tricellular stage. These results indicate that OseIF3f plays a role in microgametogenesis. PMID- 27200009 TI - Astaxanthin-Producing Green Microalga Haematococcus pluvialis: From Single Cell to High Value Commercial Products. AB - Many species of microalgae have been used as source of nutrient rich food, feed, and health promoting compounds. Among the commercially important microalgae, Haematococcus pluvialis is the richest source of natural astaxanthin which is considered as "super anti-oxidant." Natural astaxanthin produced by H. pluvialis has significantly greater antioxidant capacity than the synthetic one. Astaxanthin has important applications in the nutraceuticals, cosmetics, food, and aquaculture industries. It is now evident that, astaxanthin can significantly reduce free radicals and oxidative stress and help human body maintain a healthy state. With extraordinary potency and increase in demand, astaxanthin is one of the high-value microalgal products of the future.This comprehensive review summarizes the most important aspects of the biology, biochemical composition, biosynthesis, and astaxanthin accumulation in the cells of H. pluvialis and its wide range of applications for humans and animals. In this paper, important and recent developments ranging from cultivation, harvest and postharvest bio processing technologies to metabolic control and genetic engineering are reviewed in detail, focusing on biomass and astaxanthin production from this biotechnologically important microalga. Simultaneously, critical bottlenecks and major challenges in commercial scale production; current and prospective global market of H. pluvialis derived astaxanthin are also presented in a critical manner. A new biorefinery concept for H. pluvialis has been also suggested to guide toward economically sustainable approach for microalgae cultivation and processing. This report could serve as a useful guide to present current status of knowledge in the field and highlight key areas for future development of H. pluvialis astaxanthin technology and its large scale commercial implementation. PMID- 27200011 TI - Protection of Chloroplast Membranes by VIPP1 Rescues Aberrant Seedling Development in Arabidopsis nyc1 Mutant. AB - Chlorophylls (Chl) in photosynthetic apparatuses, along with other macromolecules in chloroplasts, are known to undergo degradation during leaf senescence. Several enzymes involved in Chl degradation, by which detoxification of Chl is safely implemented, have been identified. Chl degradation also occurs during embryogenesis and seedling development. Some genes encoding Chl degradation enzymes such as Chl b reductase (CBR) function during these developmental stages. Arabidopsis mutants lacking CBR (NYC1 and NOL) have been reported to exhibit reduced seed storability, compromised germination, and cotyledon development. In this study, we examined aberrant cotyledon development and found that NYC1 is solely responsible for this phenotype. We inferred that oxidative damage of chloroplast membranes caused the aberrant cotyledon. To test the inference, we attempted to trans-complement nyc1 mutant with overexpressing VIPP1 protein that is unrelated to Chl degradation but which supports chloroplast membrane integrity. VIPP1 expression actually complemented the aberrant cotyledon of nyc1, whereas stay-green phenotype during leaf senescence remained. The swollen chloroplasts observed in unfixed cotyledons of nyc1, which are characteristics of chloroplasts receiving envelope membrane damage, were recovered by overexpressing VIPP1. These results suggest that chloroplast membranes are a target for oxidative damage caused by the impairment in Chl degradation. Trans complementation of nyc1 with VIPP1 also suggests that VIPP1 is useful for protecting chloroplasts against oxidative stress. PMID- 27200012 TI - Genome-Wide Identification and Characterization of WRKY Gene Family in Peanut. AB - WRKY, an important transcription factor family, is widely distributed in the plant kingdom. Many reports focused on analysis of phylogenetic relationship and biological function of WRKY protein at the whole genome level in different plant species. However, little is known about WRKY proteins in the genome of Arachis species and their response to salicylic acid (SA) and jasmonic acid (JA) treatment. In this study, we identified 77 and 75 WRKY proteins from the two wild ancestral diploid genomes of cultivated tetraploid peanut, Arachis duranensis and Arachis ipaensis, using bioinformatics approaches. Most peanut WRKY coding genes were located on A. duranensis chromosome A6 and A. ipaensis chromosome B3, while the least number of WRKY genes was found in chromosome 9. The WRKY orthologous gene pairs in A. duranensis and A. ipaensis chromosomes were highly syntenic. Our analysis indicated that segmental duplication events played a major role in AdWRKY and AiWRKY genes, and strong purifying selection was observed in gene duplication pairs. Furthermore, we translate the knowledge gained from the genome wide analysis result of wild ancestral peanut to cultivated peanut to reveal that gene activities of specific cultivated peanut WRKY gene were changed due to SA and JA treatment. Peanut WRKY7, 8 and 13 genes were down-regulated, whereas WRKY1 and 12 genes were up-regulated with SA and JA treatment. These results could provide valuable information for peanut improvement. PMID- 27200015 TI - Presence of Trifolium repens Promotes Complementarity of Water Use and N Facilitation in Diverse Grass Mixtures. AB - Legume species promote productivity and increase the digestibility of herbage in grasslands. Considerable experimental data also indicate that communities with legumes produce more above-ground biomass than is expected from monocultures. While it has been attributed to N facilitation, evidence to identify the mechanisms involved is still lacking and the role of complementarity in soil water acquisition by vertical root differentiation remains unclear. We used a 20 months mesocosm experiment to investigate the effects of species richness (single species, two- and five-species mixtures) and functional diversity (presence of the legume Trifolium repens) on a set of traits related to light, N and water use and measured at community level. We found a positive effect of Trifolium presence and abundance on biomass production and complementarity effects in the two species mixtures from the second year. In addition the community traits related to water and N acquisition and use (leaf area, N, water-use efficiency, and deep root growth) were higher in the presence of Trifolium. With a multiple regression approach, we showed that the traits related to water acquisition and use were with N the main determinants of biomass production and complementarity effects in diverse mixtures. At shallow soil layers, lower root mass of Trifolium and higher soil moisture should increase soil water availability for the associated grass species. Conversely at deep soil layer, higher root growth and lower soil moisture mirror soil resource use increase of mixtures. Altogether, these results highlight N facilitation but almost soil vertical differentiation and thus complementarity for water acquisition and use in mixtures with Trifolium. Contrary to grass-Trifolium mixtures, no significant over-yielding was measured for grass mixtures even those having complementary traits (short and shallow vs. tall and deep). Thus, vertical complementarity for soil resources uptake in mixtures was not only dependant on the inherent root system architecture but also on root plasticity. We also observed a time-dependence for positive complementarity effects due to the slow development of Trifolium in mixtures, possibly induced by competition with grasses. Overall, our data underlined that soil water resource was an important driver of over-yielding and complementarity effects in Trifolium-grass mixtures. PMID- 27200014 TI - Flux Balance Analysis of Plant Metabolism: The Effect of Biomass Composition and Model Structure on Model Predictions. AB - The biomass composition represented in constraint-based metabolic models is a key component for predicting cellular metabolism using flux balance analysis (FBA). Despite major advances in analytical technologies, it is often challenging to obtain a detailed composition of all major biomass components experimentally. Studies examining the influence of the biomass composition on the predictions of metabolic models have so far mostly been done on models of microorganisms. Little is known about the impact of varying biomass composition on flux prediction in FBA models of plants, whose metabolism is very versatile and complex because of the presence of multiple subcellular compartments. Also, the published metabolic models of plants differ in size and complexity. In this study, we examined the sensitivity of the predicted fluxes of plant metabolic models to biomass composition and model structure. These questions were addressed by evaluating the sensitivity of predictions of growth rates and central carbon metabolic fluxes to varying biomass compositions in three different genome-/large-scale metabolic models of Arabidopsis thaliana. Our results showed that fluxes through the central carbon metabolism were robust to changes in biomass composition. Nevertheless, comparisons between the predictions from three models using identical modeling constraints and objective function showed that model predictions were sensitive to the structure of the models, highlighting large discrepancies between the published models. PMID- 27200013 TI - Selection and Validation of Appropriate Reference Genes for Quantitative Real Time PCR Analysis of Gene Expression in Lycoris aurea. AB - Lycoris aurea (L' Her.) Herb, a perennial grass species, produces a unique variety of pharmacologically active Amaryllidaceae alkaloids. However, the key enzymes and their expression pattern involved in the biosynthesis of Amaryllidaceae alkaloids (especially for galanthamine) are far from being fully understood. Quantitative real-time polymerase chain reaction (qRT-PCR), a commonly used method for quantifying gene expression, requires stable reference genes to normalize its data. In this study, to choose the appropriate reference genes under different experimental conditions, 14 genes including YLS8 (mitosis protein YLS8), CYP2 (Cyclophilin 2), CYP 1 (Cyclophilin 1), TIP41 (TIP41-like protein), EXP2 (Expressed protein 2), PTBP1 (Polypyrimidine tract-binding protein 1), EXP1 (Expressed protein 1), PP2A (Serine/threonine-protein phosphatase 2A), beta-TUB (beta-tubulin), alpha-TUB (alpha-tubulin), EF1-alpha (Elongation factor 1-alpha), UBC (Ubiquitin-conjugating enzyme), ACT (Actin) and GAPDH (Glyceraldehyde 3-phosphate dehydrogenase) were selected from the transcriptome datasets of L. aurea. And then, expressions of these genes were assessed by qRT PCR in various tissues and the roots under different treatments. The expression stability of the 14 candidates was analyzed by three commonly used software programs (geNorm, NormFinder, and BestKeeper), and their results were further integrated into a comprehensive ranking based on the geometric mean. The results show the relatively stable genes for each subset as follows: (1) EXP1 and TIP41 for all samples; (2) UBC and EXP1 for NaCl stress; (3) PTBP1 and EXP1 for heat stress, polyethylene glycol (PEG) stress and ABA treatment; (4) UBC and CYP2 for cold stress; (5) PTBP1 and PP2A for sodium nitroprusside (SNP) treatment; (6) CYP1 and TIP41 for methyl jasmonate (MeJA) treatment; and (7) EXP1 and TIP41 for various tissues. The reliability of these results was further enhanced through comparison between part qRT-PCR result and RNA sequencing (RNA-seq) data. In summary, our results identified appropriate reference genes for qRT-PCR in L. aurea, and will facilitate gene expression studies under these conditions. PMID- 27200016 TI - Molecular Breeding to Create Optimized Crops: From Genetic Manipulation to Potential Applications in Plant Factories. AB - Crop cultivation in controlled environment plant factories offers great potential to stabilize the yield and quality of agricultural products. However, many crops are currently unsuited to these environments, particularly closed cultivation systems, due to space limitations, low light intensity, high implementation costs, and high energy requirements. A major barrier to closed system cultivation is the high running cost, which necessitates the use of high-margin crops for economic viability. High-value crops include those with enhanced nutritional value or containing additional functional components for pharmaceutical production or with the aim of providing health benefits. In addition, it is important to develop cultivars equipped with growth parameters that are suitable for closed cultivation. Small plant size is of particular importance due to the limited cultivation space. Other advantageous traits are short production cycle, the ability to grow under low light, and high nutriculture availability. Cost effectiveness is improved from the use of cultivars that are specifically optimized for closed system cultivation. This review describes the features of closed cultivation systems and the potential application of molecular breeding to create crops that are optimized for cost-effectiveness and productivity in closed cultivation systems. PMID- 27200018 TI - Interactions of Sulfate with Other Nutrients As Revealed by H2S Fumigation of Chinese Cabbage. AB - Sulfur deficiency in plants has severe impacts on both growth and nutrient composition. Fumigation with sub-lethal concentrations of H2S facilitates the supply of reduced sulfur via the leaves while sulfate is depleted from the roots. This restores growth while sulfate levels in the plant tissue remain low. In the present study this system was used to reveal interactions of sulfur with other nutrients in the plant and to ascertain whether these changes are due to the absence or presence of sulfate or rather to changes in growth and organic sulfur. There was a complex reaction of the mineral composition to sulfur deficiency, however, the changes in content of many nutrients were prevented by H2S fumigation. Under sulfur deficiency these nutrients accumulated on a fresh weight basis but were diluted on a dry weight basis, presumably due to a higher dry matter content. The pattern differed, however, between leaves and roots which led to changes in shoot to root partitioning. Only the potassium, molybdenum and zinc contents were strongly linked to the sulfate supply. Potassium was the only nutrient amongst those measured which showed a positive correlation with sulfur content in shoots, highlighting a role as a counter cation for sulfate during xylem loading and vacuolar storage in leaves. This was supported by an accumulation of potassium in roots of the sulfur-deprived plants. Molybdenum and zinc increased substantially under sulfur deficiency, which was only partly prevented by H2S fumigation. While the causes of increased molybdenum under sulfur deficiency have been previously studied, the relation between sulfate and zinc uptake needs further clarification. PMID- 27200017 TI - Cellular and Pectin Dynamics during Abscission Zone Development and Ripe Fruit Abscission of the Monocot Oil Palm. AB - The oil palm (Elaeis guineensis Jacq.) fruit primary abscission zone (AZ) is a multi-cell layered boundary region between the pedicel (P) and mesocarp (M) tissues. To examine the cellular processes that occur during the development and function of the AZ cell layers, we employed multiple histological and immunohistochemical methods combined with confocal, electron and Fourier transform infrared (FT-IR) microspectroscopy approaches. During early fruit development and differentiation of the AZ, the orientation of cell divisions in the AZ was periclinal compared with anticlinal divisions in the P and M. AZ cell wall width increased earlier during development suggesting cell wall assembly occurred more rapidly in the AZ than the adjacent P and M tissues. The developing fruit AZ contain numerous intra-AZ cell layer plasmodesmata (PD), but very few inter-AZ cell layer PD. In the AZ of ripening fruit, PD were less frequent, wider, and mainly intra-AZ cell layer localized. Furthermore, DAPI staining revealed nuclei are located adjacent to PD and are remarkably aligned within AZ layer cells, and remain aligned and intact after cell separation. The polarized accumulation of ribosomes, rough endoplasmic reticulum, mitochondria, and vesicles suggested active secretion at the tip of AZ cells occurred during development which may contribute to the striated cell wall patterns in the AZ cell layers. AZ cells accumulated intracellular pectin during development, which appear to be released and/or degraded during cell separation. The signal for the JIM5 epitope, that recognizes low methylesterified and un-methylesterified homogalacturonan (HG), increased in the AZ layer cell walls prior to separation and dramatically increased on the separated AZ cell surfaces. Finally, FT-IR microspectroscopy analysis indicated a decrease in methylesterified HG occurred in AZ cell walls during separation, which may partially explain an increase in the JIM5 epitope signal. The results obtained through a multi-imaging approach allow an integrated view of the dynamic developmental processes that occur in a multi-layered boundary AZ and provide evidence for distinct regulatory mechanisms that underlie oil palm fruit AZ development and function. PMID- 27200019 TI - Comparative Proteomic Analysis of Two Barley Cultivars (Hordeum vulgare L.) with Contrasting Grain Protein Content. AB - Grain protein contents (GPCs) of barley seeds are significantly different between feed and malting barley cultivars. However, there is still no insight into the proteomic analysis of seed proteins between feed and malting barley cultivars. Also, the genetic control of barley GPC is still unclear. GPCs were measured between mature grains of Yangsimai 3 and Naso Nijo. A proteome profiling of differentially expressed protein was established by using a combination of 2-DE and tandem mass spectrometry. In total, 502 reproducible protein spots in barley seed proteome were detected with a pH range of 4-7 and 6-11, among these 41 protein spots (8.17%) were detected differentially expressed between Yangsimai 3 and Naso Nijo. Thirty-four protein spots corresponding to 23 different proteins were identified, which were grouped into eight categories, including stress, protein degradation and post-translational modification, development, cell, signaling, glycolysis, starch metabolism, and other functions. Among the identified proteins, enolase (spot 274) and small subunit of ADP-glucose pyrophosphorylase (spot 271) are exclusively expressed in barley Yangsimai 3, which may be involved in regulating seed protein expression. In addition, malting quality is characterized by an accumulation of serpin protein, Alpha amylase/trypsin inhibitor CMb and Alpha-amylase inhibitor BDAI-1. Most noticeably, globulin, an important storage protein in barley seed, undergoes post translational processing in both cultivars, and also displays different expression patterns. PMID- 27200020 TI - Inheritance of Resistance to Sorghum Shoot Fly, Atherigona soccata in Sorghum, Sorghum bicolor (L.) Moench. AB - Sorghum production is affected by a wide array of biotic constraints, of which sorghum shoot fly, Atherigona soccata is the most important pest, which severely damages the sorghum crop during the seedling stage. Host plant resistance is one of the major components to control sorghum shoot fly, A. soccata. To understand the nature of gene action for inheritance of shoot fly resistance, we evaluated 10 parents, 45 F1's and their reciprocals in replicated trials during the rainy and postrainy seasons. The genotypes ICSV 700, Phule Anuradha, ICSV 25019, PS 35805, IS 2123, IS 2146, and IS 18551 exhibited resistance to shoot fly damage across seasons. Crosses between susceptible parents were preferred for egg laying by the shoot fly females, resulting in a susceptible reaction. ICSV 700, ICSV 25019, PS 35805, IS 2123, IS 2146, and IS 18551 exhibited significant and negative general combining ability (gca) effects for oviposition, deadheart incidence, and overall resistance score. The plant morphological traits associated with expression of resistance/susceptibility to shoot fly damage such as leaf glossiness, plant vigor, and leafsheath pigmentation also showed significant gca effects by these genotypes, suggesting the potential for use as a selection criterion to breed for resistance to shoot fly, A. soccata. ICSV 700, Phule Anuradha, IS 2146 and IS 18551 with significant positive gca effects for trichome density can also be utilized in improving sorghums for shoot fly resistance. The parents involved in hybrids with negative specific combining ability (sca) effects for shoot fly resistance traits can be used in developing sorghum hybrids with adaptation to postrainy season. The significant reciprocal effects of combining abilities for oviposition, leaf glossy score and trichome density suggested the influence of cytoplasmic factors in inheritance of shoot fly resistance. Higher values of variance due to specific combining ability (sigma(2)s), dominance variance (sigma(2)d), and lower predictability ratios than the variance due to general combining ability (sigma(2)g) and additive variance (sigma(2)a) for shoot fly resistance traits indicated the predominance of dominance type of gene action, whereas trichome density, leaf glossy score, and plant vigor score with high sigma(2)g, additive variance, predictability ratio, and the ratio of general combining ability to the specific combining ability showed predominance of additive type of gene action indicating importance of heterosis breeding followed by simple selection in breeding shoot fly-resistant sorghums. Most of the traits exhibited high broadsense heritability, indicating high inheritance of shoot fly resistance traits. PMID- 27200021 TI - DspA/E Contributes to Apoplastic Accumulation of ROS in Non-host A. thaliana. AB - The bacterium Erwinia amylovora is responsible for the fire blight disease of Maleae, which provokes necrotic symptoms on aerial parts. The pathogenicity of this bacterium in hosts relies on its type three-secretion system (T3SS), a molecular syringe that allows the bacterium to inject effectors into the plant cell. E. amylovora-triggered disease in host plants is associated with the T3SS dependent production of reactive oxygen species (ROS), although ROS are generally associated with resistance in other pathosystems. We showed previously that E. amylovora can multiply transiently in the non-host plant Arabidopsis thaliana and that a T3SS-dependent production of intracellular ROS occurs during this interaction. In the present work we characterize the localization and source of hydrogen peroxide accumulation following E. amylovora infection. Transmission electron microscope (TEM) analysis of infected tissues showed that hydrogen peroxide accumulation occurs in the cytosol, plastids, peroxisomes, and mitochondria as well as in the apoplast. Furthermore, TEM analysis showed that an E. amylovora dspA/E-deficient strain does not induce hydrogen peroxide accumulation in the apoplast. Consistently, a transgenic line expressing DspA/E accumulated ROS in the apoplast. The NADPH oxidase-deficient rbohD mutant showed a very strong reduction in hydrogen peroxide accumulation in response to E. amylovora inoculation. However, we did not find an increase in bacterial titers of E. amylovora in the rbohD mutant and the rbohD mutation did not suppress the toxicity of DspA/E when introgressed into a DspA/E-expressing transgenic line. Co inoculation of E. amylovora with cycloheximide (CHX), which we found previously to suppress callose deposition and allow strong multiplication of E. amylovora in A. thaliana leaves, led to a strong reduction of apoplastic ROS accumulation but did not affect intracellular ROS. Our data strongly suggest that apoplastic ROS accumulation is one layer of the non-host defense response triggered by the type three effector (T3E) DspA/E, together with callose deposition. PMID- 27200022 TI - Characterization of a New Pm2 Allele Conferring Powdery Mildew Resistance in the Wheat Germplasm Line FG-1. AB - Powdery mildew has a negative impact on wheat production. Novel host resistance increases the diversity of resistance genes and helps to control the disease. In this study, wheat line FG-1 imported from France showed a high level of powdery mildew resistance at both the seedling and adult stages. An F2 population and F2:3 families from the cross FG-1 * Mingxian 169 both fit Mendelian ratios for a single dominant resistance gene when tested against multiple avirulent Blumeria tritici f. sp. tritici (Bgt) races. This gene was temporarily designated PmFG. PmFG was mapped on the multi-allelic Pm2 locus of chromosome 5DS using seven SSR, 10 single nucleotide polymorphism (SNP)-derived and two SCAR markers with the flanking markers Xbwm21/Xcfd81/Xscar112 (distal) and Xbwm25 (proximal) at 0.3 and 0.5 cM being the closest. Marker SCAR203 co-segregated with PmFG. Allelism tests between PmFG and documented Pm2 alleles confirmed that PmFG was allelic with Pm2. Line FG-1 produced a significantly different reaction pattern compared to other lines with genes at or near Pm2 when tested against 49 Bgt isolates. The PmFG linked marker alleles detected by the SNP-derived markers revealed significant variation between FG-1 and other lines with genes at or near Pm2. It was concluded that PmFG is a new allele at the Pm2 locus. Data from seven closely linked markers tested on 31 wheat cultivars indicated opportunities for marker assisted pyramiding of this gene with other genes for powdery mildew resistance and additional traits. PMID- 27200023 TI - PP2C-like Promoter and Its Deletion Variants Are Induced by ABA but Not by MeJA and SA in Arabidopsis thaliana. AB - Gene expression is mediated through interaction between cis regulatory elements and its cognate transcription factors. Cis regulatory elements are defined as non coding DNA sequences that provide the binding sites for transcription factors and are clustered in the upstream region of genes. ACGT cis regulatory element is one of the important cis regulatory elements found to be involved in diverse biological processes like auxin response, salicylic acid (SA) response, UV light response, ABA response and jasmonic acid (JA) response. We identified through in silico analysis that the upstream region of protein phosphatase 2C (PP2C) gene has a distinct genetic architecture of ACGT elements. In the present study, the activation of the full length promoter and its deletion constructs like 900 base pair, 500 base pair, 400 base pair and NRM (Nathji Rajesh Mehrotra) were examined by stable transformation in Arabidopsis thaliana using beta-glucuronidase as the reporter gene. Evaluation of deletion constructs of PP2C-like promoter was carried out in the presence of phytohormones like abscisic acid (ABA), SA and JA. Our result indicated that the full length and 900 base pair promoter-reporter constructs of PP2C-like promoter was induced in response to ABA but not to methyl jasmonate and SA. PMID- 27200024 TI - Genetic Structure of a Naturally Regenerating Post-Fire Seedling Population: Pinus halepensis As a Case Study. AB - To study the effects of wildfire on population genetics of a wind pollinated and wind dispersed tree, we have analyzed the genetic structure of a post-fire, naturally regenerating seedling population of Pinus halepensis Miller, on Mt. Carmel, Israel. We tested the existence of spatial genetic structure, which is expected due to the special spatial demographic structure of the post-fire seedling and sapling populations of this species. Explicitly, we asked whether or not seedlings that germinated under large, burned, dead pine trees are also their offspring. The results revealed that the post-fire seedling population is polymorphic, diverse, and reflects the pre-fire random mating system. In contrast to our prediction, we found no division of the post-fire seedling population to distinct sub-populations. Furthermore, as a result of post-fire seed dispersal to longer range than the average pre-fire inter-tree distance, seedlings found under individual burned trees were not necessarily their sole offspring. Although the population as a whole showed a Hardy-Weinberg equilibrium, significant excess of heterozygotes was found within each tallest seedlings group growing under single, large, burned pine trees. Our finding indicates the possible existence of intense natural selection for the most vigorous heterozygous genotypes that are best adapted to the special post-fire regeneration niche, which is the thick ash bed under large, dead, pine trees. PMID- 27200025 TI - Deciphering Phosphate Deficiency-Mediated Temporal Effects on Different Root Traits in Rice Grown in a Modified Hydroponic System. AB - Phosphate (Pi), an essential macronutrient for growth and development of plant, is often limiting in soils. Plants have evolved an array of adaptive strategies including modulation of root system architecture (RSA) for optimal acquisition of Pi. In rice, a major staple food, RSA is complex and comprises embryonically developed primary and seminal roots and post-embryonically developed adventitious and lateral roots. Earlier studies have used variant hydroponic systems for documenting the effects of Pi deficiency largely on primary root growth. Here, we report the temporal effects of Pi deficiency in rice genotype MI48 on 15 ontogenetically distinct root traits by using easy-to-assemble and economically viable modified hydroponic system. Effects of Pi deprivation became evident after 4 days- and 7 days-treatments on two and eight different root traits, respectively. The effects of Pi deprivation for 7 days were also evident on different root traits of rice genotype Nagina 22 (N22). There were genotypic differences in the responses of primary root growth along with lateral roots on it and the number and length of seminal and adventitious roots. Notably though, there were attenuating effects of Pi deficiency on the lateral roots on seminal and adventitious roots and total root length in both these genotypes. The study thus revealed both differential and comparable effects of Pi deficiency on different root traits in these genotypes. Pi deficiency also triggered reduction in Pi content and induction of several Pi starvation-responsive (PSR) genes in roots of MI48. Together, the analyses validated the fidelity of this modified hydroponic system for documenting Pi deficiency-mediated effects not only on different traits of RSA but also on physiological and molecular responses. PMID- 27200026 TI - Roles of Clonal Integration in both Heterogeneous and Homogeneous Habitats. AB - Many studies have shown that clonal integration can promote the performance of clonal plants in heterogeneous habitats, but the roles of clonal integration in both heterogeneous and homogeneous habitats were rarely studied simultaneously. Ramet pairs of Alternanthera philoxeroides (Mart.) Griseb were placed in two habitats either heterogeneous or homogeneous in soil nutrient availability, with stolon connections left intact or severed. Total biomass, total length of stolons, and number of new ramets of distal (relatively young) ramets located in low-nutrient environments were significantly greater when the distal ramets were connected to than when they were disconnected from proximal (relatively old) ramets located in high-nutrient environments. Total length of stolons of proximal ramets growing in low-nutrient environments was significantly higher when the proximal ramets were connected to than when they were disconnected from the distal ramets growing in high-nutrient environments, but stolon connection did not affect total biomass or number of new ramets of the proximal ramets. Stolon severing also did not affect the growth of the whole ramet pairs in heterogeneous environments. In homogeneous high-nutrient environments stolon severing promoted the growth of the proximal ramets and the ramet pairs, but in homogeneous low nutrient environments it did not affect the growth of the proximal or distal ramets. Hence, for A. philoxeroides, clonal fragmentation appears to be more advantageous than clonal integration in resource-rich homogeneous habitats, and clonal integration becomes beneficial in heterogeneous habitats. Our study contributes to revealing roles of clonal integration in both heterogeneous and homogeneous habitats and expansion patterns of invasive clonal plants such as A. philoxeroides in multifarious habitats. PMID- 27200027 TI - Water Stress Modulates Soybean Aphid Performance, Feeding Behavior, and Virus Transmission in Soybean. AB - Little is known about how water stress including drought and flooding modifies the ability of plants to resist simultaneous attack by insect feeding and transmission of insect-vectored pathogen. We analyzed insect population growth, feeding behaviors, virus transmission, and plant amino acid profiles and defense gene expression to characterize mechanisms underlying the interaction between water stress, soybean aphid and aphid-transmitted, Soybean mosaic virus, on soybean plants. Population growth of non-viruliferous aphids was reduced under drought stress and saturation, likely because the aphids spent less time feeding from the sieve element on these plants compared to well-watered plants. Water stress did not impact population growth of viruliferous aphids. However, virus incidence and transmission rate was lowest under drought stress and highest under saturated conditions since viruliferous aphids took the greatest amount time to puncture cells and transmit the virus under saturated conditions and lowest time under drought stress. Petiole exudates from drought-stressed plants had the highest level of total free amino acids including asparagine and valine that are critical for aphid performance. Aphids did not benefit from improved phloem sap quality as indicated by their lower densities on drought-stressed plants. Saturation, on the other hand, resulted in low amino acid content compared to all of the other treatments. Drought and saturation had significant and opposing effects on expression of marker genes involved in abscisic acid (ABA) signaling. Drought alone significantly increased expression of ABA marker genes, which likely led to suppression of salicylic acid (SA)- and jasmonic acid (JA)-related genes. In contrast, ABA marker genes were down-regulated under saturation, while expression of SA- and JA-related genes was up-regulated. We propose that the apparent antagonism between ABA and SA/JA signaling pathways contributed to an increase in aphid densities under drought and their decrease under saturation. Taken together, our findings suggests that plant responses to water stress is complex involving changes in phloem amino acid composition and signaling pathways, which can impact aphid populations and virus transmission. PMID- 27200028 TI - Comparative Genomics of Botrytis cinerea Strains with Differential Multi-Drug Resistance. PMID- 27200030 TI - Future Climate CO2 Levels Mitigate Stress Impact on Plants: Increased Defense or Decreased Challenge? AB - Elevated atmospheric CO2 can stimulate plant growth by providing additional C (fertilization effect), and is observed to mitigate abiotic stress impact. Although, the mechanisms underlying the stress mitigating effect are not yet clear, increased antioxidant defenses, have been held primarily responsible (antioxidant hypothesis). A systematic literature analysis, including "all" papers [Web of Science (WoS)-cited], addressing elevated CO2 effects on abiotic stress responses and antioxidants (105 papers), confirms the frequent occurrence of the stress mitigation effect. However, it also demonstrates that, in stress conditions, elevated CO2 is reported to increase antioxidants, only in about 22% of the observations (e.g., for polyphenols, peroxidases, superoxide dismutase, monodehydroascorbate reductase). In most observations, under stress and elevated CO2 the levels of key antioxidants and antioxidant enzymes are reported to remain unchanged (50%, e.g., ascorbate peroxidase, catalase, ascorbate), or even decreased (28%, e.g., glutathione peroxidase). Moreover, increases in antioxidants are not specific for a species group, growth facility, or stress type. It seems therefore unlikely that increased antioxidant defense is the major mechanism underlying CO2-mediated stress impact mitigation. Alternative processes, probably decreasing the oxidative challenge by reducing ROS production (e.g., photorespiration), are therefore likely to play important roles in elevated CO2 (relaxation hypothesis). Such parameters are however rarely investigated in connection with abiotic stress relief. Understanding the effect of elevated CO2 on plant growth and stress responses is imperative to understand the impact of climate changes on plant productivity. PMID- 27200029 TI - Genome-Wide Analysis of Gene Regulatory Networks of the FVE-HDA6-FLD Complex in Arabidopsis. AB - FVE/MSI4 is a homolog of the mammalian RbAp48 protein. We found that FVE regulates flowering time by repressing FLC through decreasing histone H3K4 trimethylation and H3 acetylation. Furthermore, FVE interacts with the histone deacetylase HDA6 and the histone demethylase FLD, suggesting that these proteins may form a protein complex to regulate flowering time. To further investigate the function of the FVE-FLD-HDA6 complex, we compared the gene expression profiles of fve, fld, and hda6 mutant plants by using RNA-seq analysis. Among the mis regulated genes found in fve plants, 51.8 and 36.5% of them were also mis regulated in fld and hda6 plants, respectively, suggesting that FVE, HDA6, and FLD may regulate the gene expression in the same developmental processes in Arabidopsis. Gene ontology analysis revealed that among 383 genes co-regulated by FVE, HDA6, and FLD, 15.6% of them are involved in transcription, 8.2% in RNA metabolic process, 7.7% in response to abiotic stress, and 6.3% in hormone stimulus. Taken together, these results indicate that HDA6, FVE, and FLD co regulate the gene expression in multiple development processes and pathways. PMID- 27200031 TI - Thidiazuron Triggers Morphogenesis in Rosa canina L. Protocorm-Like Bodies by Changing Incipient Cell Fate. AB - Thidiazuron (N-phenyl-N'-1,2,3-thiadiazol-5-ylurea; TDZ) is an artificial plant growth regulator that is widely used in plant tissue culture. Protocorm-like bodies (PLBs) induced by TDZ serve as an efficient and rapid in vitro regeneration system in Rosa species. Despite this, the mechanism of PLB induction remains relatively unclear. TDZ, which can affect the level of endogenous auxins and cytokinins, converts the cell fate of rhizoid tips and triggers PLB formation and plantlet regeneration in Rosa canina L. In callus-rhizoids, which are rhizoids that co-develop from callus, auxin and a Z-type cytokinin accumulated after applying TDZ, and transcription of the auxin transporter gene RcPIN1 was repressed. The expression of RcARF4, RcRR1, RcCKX2, RcCKX3, and RcLOG1 increased in callus-rhizoids and rhizoid tips while the transcription of an auxin response factor (RcARF1) and auxin transport proteins (RcPIN2, RcPIN3) decreased in callus rhizoids but increased in rhizoid tips. In situ hybridization of rhizoids showed that RcWUS and RcSERK1 were highly expressed in columella cells and root stem cells resulting in the conversion of cell fate into shoot apical meristems or embryogenic callus. In addition, transgenic XVE::RcWUS lines showed repressed RcWUS overexpression while RcWUS had no effect on PLB morphogenesis. Furthermore, higher expression of the root stem cell marker RcWOX5 and root stem cell maintenance regulator genes RcPLT1 and RcPLT2 indicated the presence of a dedifferentiation developmental pathway in the stem cell niche of rhizoids. Viewed together, our results indicate that different cells in rhizoid tips acquired regeneration competence after induction by TDZ. A novel developmental pathway containing different cell types during PLB formation was identified by analyzing the endogenous auxin and cytokinin content. This study also provides a deeper understanding of the mechanisms underlying in vitro regeneration in Rosa. PMID- 27200032 TI - Conservation Strategies in the Genus Hypericum via Cryogenic Treatment. AB - In the genus Hypericum, cryoconservation offers a strategy for maintenance of remarkable biodiversity, emerging from large inter- and intra-specific variability in morphological and phytochemical characteristics. Long-term cryostorage thus represents a proper tool for preservation of genetic resources of endangered and threatened Hypericum species or new somaclonal variants with unique properties. Many representatives of the genus are known as producers of pharmacologically important polyketides, namely naphthodianthrones and phloroglucinols. As a part of numerous in vitro collections, the nearly cosmopolitan Hypericum perforatum - Saint John's wort - has become a suitable model system for application of biotechnological approaches providing an attractive alternative to the traditional methods for secondary metabolite production. The necessary requirements for efficient cryopreservation include a high survival rate along with an unchanged biochemical profile of plants regenerated from cryopreserved cells. Understanding of the processes which are critical for recovery of H. perforatum cells after the cryogenic treatment enables establishment of cryopreservation protocols applicable to a broad number of Hypericum species. Among them, several endemic taxa attract a particular attention due to their unique characteristics or yet unrevealed spectrum of bioactive compounds. In this review, recent advances in the conventional two-step and vitrification-based cryopreservation techniques are presented in relation to the recovery rate and biosynthetic capacity of Hypericum spp. The pre-cryogenic treatments which were identified to be crucial for successful post-cryogenic recovery are discussed. Being a part of genetic predisposition, the freezing tolerance as a necessary precondition for successful post-cryogenic recovery is pointed out. Additionally, a beneficial influence of cold stress on modulating naphthodianthrone biosynthesis is outlined. PMID- 27200033 TI - Corrigendum: Zinc Oxide Nanoparticles Affect Biomass Accumulation and Photosynthesis in Arabidopsis. AB - [This corrects the article on p. 1243 in vol. 6, PMID: 26793220.]. PMID- 27200034 TI - Hypericin in the Light and in the Dark: Two Sides of the Same Coin. AB - Hypericin (4,5,7,4',5',7'-hexahydroxy-2,2'-dimethylnaphtodianthrone) is a naturally occurring chromophore found in some species of the genus Hypericum, especially Hypericum perforatum L. (St. John's wort), and in some basidiomycetes (Dermocybe spp.) or endophytic fungi (Thielavia subthermophila). In recent decades, hypericin has been intensively studied for its broad pharmacological spectrum. Among its antidepressant and light-dependent antiviral actions, hypericin is a powerful natural photosensitizer that is applicable in the photodynamic therapy (PDT) of various oncological diseases. As the accumulation of hypericin is significantly higher in neoplastic tissue than in normal tissue, it can be used in photodynamic diagnosis (PDD) as an effective fluorescence marker for tumor detection and visualization. In addition, light-activated hypericin acts as a strong pro-oxidant agent with antineoplastic and antiangiogenic properties, since it effectively induces the apoptosis, necrosis or autophagy of cancer cells. Moreover, a strong affinity of hypericin for necrotic tissue was discovered. Thus, hypericin and its radiolabeled derivatives have been recently investigated as potential biomarkers for the non-invasive targeting of tissue necrosis in numerous disorders, including solid tumors. On the other hand, several light-independent actions of hypericin have also been described, even though its effects in the dark have not been studied as intensively as those of photoactivated hypericin. Various experimental studies have revealed no cytotoxicity of hypericin in the dark; however, it can serve as a potential antimetastatic and antiangiogenic agent. On the contrary, hypericin can induce the expression of some ABC transporters, which are often associated with the multidrug resistance (MDR) of cancer cells. Moreover, the hypericin mediated attenuation of the cytotoxicity of some chemotherapeutics was revealed. Therefore, hypericin might represent another St. John's wort metabolite that is potentially responsible for negative herb-drug interactions. The main aim of this review is to summarize the benefits of photoactivated and non-activated hypericin, mainly in preclinical and clinical applications, and to uncover the "dark side" of this secondary metabolite, focusing on MDR mechanisms. PMID- 27200035 TI - Evolution of the Cp-Actin-based Motility System of Chloroplasts in Green Plants. AB - During the course of green plant evolution, numerous light responses have arisen that optimize their growth under fluctuating light conditions. The blue light receptor phototropin mediates several photomovement responses at the tissue, cellular and organelle levels. Chloroplast photorelocation movement is one such photomovement response, and is found not only in most green plants, but also in some red algae and photosynthetic stramenopiles. In general, chloroplasts move toward weak light to maximally capture photosynthetically active radiation (the chloroplast accumulation response), and they move away from strong light to avoid photodamage (the avoidance response). In land plants, chloroplast movement is dependent on specialized actin filaments, chloroplast-actin filaments (cp-actin filaments). Through molecular genetic analysis using Arabidopsis thaliana, many molecular factors that regulate chloroplast photorelocation were identified. In this Perspective, we discuss the evolutionary history of the molecular mechanism for chloroplast photorelocation movement in green plants in view of cp-actin filaments. PMID- 27200037 TI - In vivo Observation of Tree Drought Response with Low-Field NMR and Neutron Imaging. AB - Using a simple low-field NMR system, we monitored water content in a living tree in a greenhouse over 2 months. By continuously running the system, we observed changes in tree water content on a scale of half an hour. The data showed a diurnal change in water content consistent both with previous NMR and biological observations. Neutron imaging experiments show that our NMR signal is primarily due to water being rapidly transported through the plant, and not to other sources of hydrogen, such as water in cytoplasm, or water in cell walls. After accounting for the role of temperature in the observed NMR signal, we demonstrate a change in the diurnal signal behavior due to simulated drought conditions for the tree. These results illustrate the utility of our system to perform noninvasive measurements of tree water content outside of a temperature controlled environment. PMID- 27200036 TI - Phloem Proteomics Reveals New Lipid-Binding Proteins with a Putative Role in Lipid-Mediated Signaling. AB - Global climate changes inversely affect our ability to grow the food required for an increasing world population. To combat future crop loss due to abiotic stress, we need to understand the signals responsible for changes in plant development and the resulting adaptations, especially the signaling molecules traveling long distance through the plant phloem. Using a proteomics approach, we had identified several putative lipid-binding proteins in the phloem exudates. Simultaneously, we identified several complex lipids as well as jasmonates. These findings prompted us to propose that phloem (phospho-) lipids could act as long-distance developmental signals in response to abiotic stress, and that they are released, sensed, and moved by phloem lipid-binding proteins (Benning et al., 2012). Indeed, the proteins we identified include lipases that could release a signaling lipid into the phloem, putative receptor components, and proteins that could mediate lipid-movement. To test this possible protein-based lipid-signaling pathway, three of the proteins, which could potentially act in a relay, are characterized here: (I) a putative GDSL-motif lipase (II) a PIG-P-like protein, with a possible receptor-like function; (III) and PLAFP (phloem lipid-associated family protein), a predicted lipid-binding protein of unknown function. Here we show that all three proteins bind lipids, in particular phosphatidic acid (PtdOH), which is known to participate in intracellular stress signaling. Genes encoding these proteins are expressed in the vasculature, a prerequisite for phloem transport. Cellular localization studies show that the proteins are not retained in the endoplasmic reticulum but surround the cell in a spotted pattern that has been previously observed with receptors and plasmodesmatal proteins. Abiotic signals that induce the production of PtdOH also regulate the expression of GDSL-lipase and PLAFP, albeit in opposite patterns. Our findings suggest that while all three proteins are indeed lipid-binding and act in the vasculature possibly in a function related to long-distance signaling, the three proteins do not act in the same but rather in distinct pathways. It also points toward PLAFP as a prime candidate to investigate long-distance lipid signaling in the plant drought response. PMID- 27200038 TI - Linking Jasmonic Acid to Grapevine Resistance against the Biotrophic Oomycete Plasmopara viticola. AB - Plant resistance to biotrophic pathogens is classically believed to be mediated through salicylic acid (SA) signaling leading to hypersensitive response followed by the establishment of Systemic Acquired Resistance. Jasmonic acid (JA) signaling has extensively been associated to the defense against necrotrophic pathogens and insects inducing the accumulation of secondary metabolites and PR proteins. Moreover, it is believed that plants infected with biotrophic fungi suppress JA-mediated responses. However, recent evidences have shown that certain biotrophic fungal species also trigger the activation of JA-mediated responses, suggesting a new role for JA in the defense against fungal biotrophs. Plasmopara viticola is a biotrophic oomycete responsible for the grapevine downy mildew, one of the most important diseases in viticulture. In this perspective, we show recent evidences of JA participation in grapevine resistance against P. viticola, outlining the hypothesis of JA involvement in the establishment of an incompatible interaction with this biotroph. We also show that in the first hours after P. viticola inoculation the levels of OPDA, JA, JA-Ile, and SA increase together with an increase of expression of genes associated to JA and SA signaling pathways. Our data suggests that, on the first hours after P. viticola inoculation, JA signaling pathway is activated and the outcomes of JA-SA interactions may be tailored in the defense response against this biotrophic pathogen. PMID- 27200039 TI - Orthology Analysis and In Vivo Complementation Studies to Elucidate the Role of DIR1 during Systemic Acquired Resistance in Arabidopsis thaliana and Cucumis sativus. AB - AtDIR1 (Defective in Induced Resistance1) is an acidic lipid transfer protein essential for systemic acquired resistance (SAR) in Arabidopsis thaliana. Upon SAR induction, DIR1 moves from locally infected to distant uninfected leaves to activate defense priming; however, a molecular function for DIR1 has not been elucidated. Bioinformatic analysis and in silico homology modeling identified putative AtDIR1 orthologs in crop species, revealing conserved protein motifs within and outside of DIR1's central hydrophobic cavity. In vitro assays to compare the capacity of recombinant AtDIR1 and targeted AtDIR1-variant proteins to bind the lipophilic probe TNS (6,P-toluidinylnaphthalene-2-sulfonate) provided evidence that conserved leucine 43 and aspartic acid 39 contribute to the size of the DIR1 hydrophobic cavity and possibly hydrophobic ligand binding. An Arabidopsis-cucumber SAR model was developed to investigate the conservation of DIR1 function in cucumber (Cucumis sativus), and we demonstrated that phloem exudates from SAR-induced cucumber rescued the SAR defect in the Arabidopsis dir1 1 mutant. Additionally, an AtDIR1 antibody detected a protein of the same size as AtDIR1 in SAR-induced cucumber phloem exudates, providing evidence that DIR1 function during SAR is conserved in Arabidopsis and cucumber. In vitro TNS displacement assays demonstrated that recombinant AtDIR1 did not bind the SAR signals azelaic acid (AzA), glycerol-3-phosphate or pipecolic acid. However, recombinant CsDIR1 and CsDIR2 interacted weakly with AzA and pipecolic acid. Bioinformatic and functional analyses using the Arabidopsis-cucumber SAR model provide evidence that DIR1 orthologs exist in tobacco, tomato, cucumber, and soybean, and that DIR1-mediated SAR signaling is conserved in Arabidopsis and cucumber. PMID- 27200040 TI - Trait Specific Expression Profiling of Salt Stress Responsive Genes in Diverse Rice Genotypes as Determined by Modified Significance Analysis of Microarrays. AB - Stress responsive gene expression is commonly profiled in a comparative manner involving different stress conditions or genotypes with contrasting reputation of tolerance/resistance. In contrast, this research exploited a wide natural variation in terms of taxonomy, origin and salt sensitivity in eight genotypes of rice to identify the trait specific patterns of gene expression under salt stress. Genome wide transcptomic responses were interrogated by the weighted continuous morpho-physiological trait responses using modified Significance Analysis of Microarrays. More number of genes was found to be differentially expressed under salt stressed compared to that of under unstressed conditions. Higher numbers of genes were observed to be differentially expressed for the traits shoot Na(+)/K(+), shoot Na(+), root K(+), biomass and shoot Cl(-), respectively. The results identified around 60 genes to be involved in Na(+), K(+), and anion homeostasis, transport, and transmembrane activity under stressed conditions. Gene Ontology (GO) enrichment analysis identified 1.36% (578 genes) of the entire transcriptome to be involved in the major molecular functions such as signal transduction (>150 genes), transcription factor (81 genes), and translation factor activity (62 genes) etc., under salt stress. Chromosomal mapping of the genes suggests that majority of the genes are located on chromosomes 1, 2, 3, 6, and 7. The gene network analysis showed that the transcription factors and translation initiation factors formed the major gene networks and are mostly active in nucleus, cytoplasm and mitochondria whereas the membrane and vesicle bound proteins formed a secondary network active in plasma membrane and vacuoles. The novel genes and the genes with unknown functions thus identified provide picture of a synergistic salinity response representing the potentially fundamental mechanisms that are active in the wide natural genetic background of rice and will be of greater use once their roles are functionally verified. PMID- 27200041 TI - Propagule Pressure, Habitat Conditions and Clonal Integration Influence the Establishment and Growth of an Invasive Clonal Plant, Alternanthera philoxeroides. AB - Many notorious invasive plants are clonal, spreading mainly by vegetative propagules. Propagule pressure (the number of propagules) may affect the establishment, growth, and thus invasion success of these clonal plants, and such effects may also depend on habitat conditions. To understand how propagule pressure, habitat conditions and clonal integration affect the establishment and growth of the invasive clonal plants, an 8-week greenhouse with an invasive clonal plant, Alternanthera philoxeroides was conducted. High (five fragments) or low (one fragment) propagule pressure was established either in bare soil (open habitat) or dense native vegetation of Jussiaea repens (vegetative habitat), with the stolon connections either severed from or connected to the relatively older ramets. High propagule pressure greatly increased the establishment and growth of A. philoxeroides, especially when it grew in vegetative habitats. Surprisingly, high propagule pressure significantly reduced the growth of individual plants of A. philoxeroides in open habitats, whereas it did not affect the individual growth in vegetative habitats. A shift in the intraspecific interaction on A. philoxeroides from competition in open habitats to facilitation in vegetative habitats may be the main reason. Moreover, clonal integration significantly improved the growth of A. philoxeroides only in open habitats, especially with low propagule pressure, whereas it had no effects on the growth and competitive ability of A. philoxeroides in vegetative habitats, suggesting that clonal integration may be of most important for A. philoxeroides to explore new open space and spread. These findings suggest that propagule pressure may be crucial for the invasion success of A. philoxeroides, and such an effect also depends on habitat conditions. PMID- 27200042 TI - Fruit Calcium: Transport and Physiology. AB - Calcium has well-documented roles in plant signaling, water relations and cell wall interactions. Significant research into how calcium impacts these individual processes in various tissues has been carried out; however, the influence of calcium on fruit ripening has not been thoroughly explored. Here, we review the current state of knowledge on how calcium may impact the development, physical traits and disease susceptibility of fruit through facilitating developmental and stress response signaling, stabilizing membranes, influencing water relations and modifying cell wall properties through cross-linking of de-esterified pectins. We explore the involvement of calcium in hormone signaling integral to the physiological mechanisms behind common disorders that have been associated with fruit calcium deficiency (e.g., blossom end rot in tomatoes or bitter pit in apples). This review works toward an improved understanding of how the many roles of calcium interact to influence fruit ripening, and proposes future research directions to fill knowledge gaps. Specifically, we focus mostly on grapes and present a model that integrates existing knowledge around these various functions of calcium in fruit, which provides a basis for understanding the physiological impacts of sub-optimal calcium nutrition in grapes. Calcium accumulation and distribution in fruit is shown to be highly dependent on water delivery and cell wall interactions in the apoplasm. Localized calcium deficiencies observed in particular species or varieties can result from differences in xylem morphology, fruit water relations and pectin composition, and can cause leaky membranes, irregular cell wall softening, impaired hormonal signaling and aberrant fruit development. We propose that the role of apoplasmic calcium-pectin crosslinking, particularly in the xylem, is an understudied area that may have a key influence on fruit water relations. Furthermore, we believe that improved knowledge of the calcium-regulated signaling pathways that control ripening would assist in addressing calcium deficiency disorders and improving fruit pathogen resistance. PMID- 27200045 TI - Carbon Monoxide as a Signaling Molecule in Plants. AB - Carbon monoxide (CO), a gaseous molecule, has emerged as a signaling molecule in plants, due to its ability to trigger a series of physiological reactions. This article provides a brief update on the synthesis of CO, its physiological functions in plant growth and development, as well as its roles in abiotic stress tolerance such as drought, salt, ultraviolet radiation, and heavy metal stress. CO has positive effects on seed germination, root development, and stomatal closure. Also, CO can enhance plant abiotic stress resistance commonly through the enhancement of antioxidant defense system. Moreover, CO shows cross talk with other signaling molecules including NO, phytohormones (IAA, ABA, and GA) and other gas signaling molecules (H2S, H2, CH4). PMID- 27200043 TI - Cross Talk between H2O2 and Interacting Signal Molecules under Plant Stress Response. AB - It is well established that oxidative stress is an important cause of cellular damage. During stress conditions, plants have evolved regulatory mechanisms to adapt to various environmental stresses. One of the consequences of stress is an increase in the cellular concentration of reactive oxygen species, which is subsequently converted to H2O2. H2O2 is continuously produced as the byproduct of oxidative plant aerobic metabolism. Organelles with a high oxidizing metabolic activity or with an intense rate of electron flow, such as chloroplasts, mitochondria, or peroxisomes are major sources of H2O2 production. H2O2 acts as a versatile molecule because of its dual role in cells. Under normal conditions, H2O2 immerges as an important factor during many biological processes. It has been established that it acts as a secondary messenger in signal transduction networks. In this review, we discuss potential roles of H2O2 and other signaling molecules during various stress responses. PMID- 27200046 TI - Comparative Proteomic Analysis of Soybean Leaves and Roots by iTRAQ Provides Insights into Response Mechanisms to Short-Term Salt Stress. AB - Salinity severely threatens land use capability and crop yields worldwide. Understanding the mechanisms that protect soybeans from salt stress will help in the development of salt-stress tolerant leguminous plants. Here we initially analyzed the changes in malondialdehyde levels, the activities of superoxide dismutase and peroxidases, chlorophyll content, and Na(+)/K(+) ratios in leaves and roots from soybean seedlings treated with 200 mM NaCl at different time points. We found that the 200 mM NaCl treated for 12 h was optimal for undertaking a proteomic analysis on soybean seedlings. An iTRAQ-based proteomic approach was used to investigate the proteomes of soybean leaves and roots under salt treatment. These data are available via ProteomeXchange with the identifier PXD002851. In total, 278 and 440 proteins with significantly altered abundances were identified in leaves and roots of soybean, respectively. From these data, a total of 50 proteins were identified in the both tissues. These differentially expressed proteins (DEPs) were from 13 biological processes. Moreover, protein protein interaction analysis revealed that proteins involved in metabolism, carbohydrate and energy metabolism, protein synthesis and redox homeostasis could be assigned to four high salt stress response networks. Furthermore, semi quantitative RT-PCR analysis revealed that some of the proteins, such as a 14-3 3, MMK2, PP1, TRX-h, were also regulated by salt stress at the level of transcription. These results indicated that effective regulatory protein expression related to signaling, membrane and transport, stress defense and metabolism all played important roles in the short-term salt response of soybean seedlings. PMID- 27200047 TI - Genome-Wide Identification and Expression Profile of Dof Transcription Factor Gene Family in Pepper (Capsicum annuum L.). AB - Dof (DNA-binding One Zinc Finger) transcription factor family is unique to plants and has diverse roles associated with plant-specific phenomena, such as light, phytohormone and defense responses as well as seed development and germination. Although, genome-wide analysis of this family has been performed in many species, information regarding Dof genes in the pepper, Capsicum annuum L., is extremely limited. In this study, exhaustive searches of pepper genome revealed 33 potential CaDofs that were phylogenetically clustered into four subgroups. Twenty nine of the 33 Dof genes could be mapped on 11 chromosomes, except for chromosome 7. The intron/exon organizations and conserved motif compositions of these genes were also analyzed. Additionally, phylogenetic analysis and classification of the Dof transcription factor family in eight plant species revealed that S. lycopersicum and C. annuum as well as O. sativa and S. bicolor Dof proteins may have evolved conservatively. Moreover, comprehensive expression analysis of CaDofs using a RNA-seq atlas and quantitative real-time polymerase chain reaction (qRT-PCR) revealed that these genes exhibit a variety of expression patterns. Most of the CaDofs were expressed in at least one of the tissues tested, whereas several genes were identified as being highly responsive to heat and salt stresses. Overall, this study describes the first genome-wide analysis of the pepper Dof family, whose genes exhibited different expression patterns in all primary fruit developmental stages and tissue types, as in response to abiotic stress. In particular, some Dof genes might be used as biomarkers for heat and salt stress. The results could expand our understanding of the roles of Dof genes in pepper. PMID- 27200048 TI - Exogenous Melatonin Improves Antioxidant Defense in Cucumber Seeds (Cucumis sativus L.) Germinated under Chilling Stress. AB - The relationship between exogenous melatonin applied into cucumber seeds during osmopriming and modifications of their antioxidant defense was studied. Accumulation of hydrogen peroxide, antioxidant enzyme activities and glutathione pool were investigated in embryonic axes isolated from the control, osmoprimed, and osmoprimed with melatonin seeds. Germinating cucumber seeds are very sensitive to chilling. Temperature 10 degrees C causes oxidative stress in young seedlings. Seed pre-treatment with melatonin seemed to limit H2O2 accumulation during germination under optimal condition as well as during chilling stress and recovery period. Melatonin affected superoxide dismutase (SOD) activity and its isoforms during stress and recovery period but did not influence CAT and POX activities. Thus it is possible that in cucumber this indoleamine could act mostly as a direct H2O2 scavenger, but superoxide anion combat via SOD stimulation. The GSH/GSSG ratio is considered as an indirect determinant of oxidative stress. When the cells are exposed to oxidative stress GSSG is accumulated and the ratio of GSH to GSSG decreases. In our research pre-sowing melatonin application into the cucumber seeds caused high beneficial value of GSH/GSSG ratio that could be helpful for stress countering. Glutathione reductase (GSSG-R) activity in the axes isolated from these seeds was two fold higher than in those isolated from the control and from the osmoprimed without melatonin ones. Additional isoforms of GSSG-R in melatonin treated seeds were also observed. It explains high and effective GSH pool restoration in the seeds pre treated with melatonin. We confirmed that melatonin could protect cucumber seeds and young seedlings against oxidative stress directly and indirectly detoxifying ROS, thereby plants grown better even in harmful environmental conditions. This work is the first that investigated on plant in vivo model and documented melatonin influence on redox state during seed germination. This way we try to fill lack of information about melatonin-regulated pathways involved in antioxidant strategy of plant defense. PMID- 27200044 TI - Abscisic Acid and Abiotic Stress Tolerance in Crop Plants. AB - Abiotic stress is a primary threat to fulfill the demand of agricultural production to feed the world in coming decades. Plants reduce growth and development process during stress conditions, which ultimately affect the yield. In stress conditions, plants develop various stress mechanism to face the magnitude of stress challenges, although that is not enough to protect them. Therefore, many strategies have been used to produce abiotic stress tolerance crop plants, among them, abscisic acid (ABA) phytohormone engineering could be one of the methods of choice. ABA is an isoprenoid phytohormone, which regulates various physiological processes ranging from stomatal opening to protein storage and provides adaptation to many stresses like drought, salt, and cold stresses. ABA is also called an important messenger that acts as the signaling mediator for regulating the adaptive response of plants to different environmental stress conditions. In this review, we will discuss the role of ABA in response to abiotic stress at the molecular level and ABA signaling. The review also deals with the effect of ABA in respect to gene expression. PMID- 27200049 TI - In Search of Enzymes with a Role in 3', 5'-Cyclic Guanosine Monophosphate Metabolism in Plants. AB - In plants, nitric oxide (NO)-mediated 3', 5'-cyclic guanosine monophosphate (cGMP) synthesis plays an important role during pathogenic stress response, stomata closure upon osmotic stress, the development of adventitious roots and transcript regulation. The NO-cGMP dependent pathway is well characterized in mammals. The binding of NO to soluble guanylate cyclase enzymes (GCs) initiates the synthesis of cGMP from guanosine triphosphate. The produced cGMP alters various cellular responses, such as the function of protein kinase activity, cyclic nucleotide gated ion channels and cGMP-regulated phosphodiesterases. The signal generated by the second messenger is terminated by 3', 5'-cyclic nucleotide phosphodiesterase (PDEs) enzymes that hydrolyze cGMP to a non-cyclic 5'-guanosine monophosphate. To date, no homologues of mammalian cGMP-synthesizing and degrading enzymes have been found in higher plants. In the last decade, six receptor proteins from Arabidopsis thaliana have been reported to have guanylate cyclase activity in vitro. Of the six receptors, one was shown to be a NO dependent guanylate cyclase enzyme (NOGC1). However, the role of these proteins in planta remains to be elucidated. Enzymes involved in the degradation of cGMP remain elusive, albeit, PDE activity has been detected in crude protein extracts from various plants. Additionally, several research groups have partially purified and characterized PDE enzymatic activity from crude protein extracts. In this review, we focus on presenting advances toward the identification of enzymes involved in the cGMP metabolism pathway in higher plants. PMID- 27200050 TI - MYB Transcription Factors in Chinese Pear (Pyrus bretschneideri Rehd.): Genome Wide Identification, Classification, and Expression Profiling during Fruit Development. AB - The MYB family is one of the largest families of transcription factors in plants. Although, some MYBs were reported to play roles in secondary metabolism, no comprehensive study of the MYB family in Chinese pear (Pyrus bretschneideri Rehd.) has been reported. In the present study, we performed genome-wide analysis of MYB genes in Chinese pear, designated as PbMYBs, including analyses of their phylogenic relationships, structures, chromosomal locations, promoter regions, GO annotations, and collinearity. A total of 129 PbMYB genes were identified in the pear genome and were divided into 31 subgroups based on phylogenetic analysis. These PbMYBs were unevenly distributed among 16 chromosomes (total of 17 chromosomes). The occurrence of gene duplication events indicated that whole genome duplication and segmental duplication likely played key roles in expansion of the PbMYB gene family. Ka/Ks analysis suggested that the duplicated PbMYBs mainly experienced purifying selection with restrictive functional divergence after the duplication events. Interspecies microsynteny analysis revealed maximum orthology between pear and peach, followed by plum and strawberry. Subsequently, the expression patterns of 20 PbMYB genes that may be involved in lignin biosynthesis according to their phylogenetic relationships were examined throughout fruit development. Among the 20 genes examined, PbMYB25 and PbMYB52 exhibited expression patterns consistent with the typical variations in the lignin content previously reported. Moreover, sub-cellular localization analysis revealed that two proteins PbMYB25 and PbMYB52 were localized to the nucleus. All together, PbMYB25 and PbMYB52 were inferred to be candidate genes involved in the regulation of lignin biosynthesis during the development of pear fruit. This study provides useful information for further functional analysis of the MYB gene family in pear. PMID- 27200052 TI - Climatic Signals from Intra-annual Density Fluctuation Frequency in Mediterranean Pines at a Regional Scale. AB - Tree rings provide information about the climatic conditions during the growing season by recording them in different anatomical features, such as intra-annual density fluctuations (IADFs). IADFs are intra-annual changes of wood density appearing as latewood-like cells within earlywood, or earlywood-like cells within latewood. The occurrence of IADFs is dependent on the age and size of the tree, and it is triggered by climatic drivers. The variations of IADF frequency of different species and their dependence on climate across a wide geographical range have still to be explored. The objective of this study is to investigate the effect of age, tree-ring width and climate on IADF formation and frequency at a regional scale across the Mediterranean Basin in Pinus halepensis Mill., Pinus pinaster Ait., and Pinus pinea L. The analyzed tree-ring network was composed of P. pinea trees growing at 10 sites (2 in Italy, 4 in Spain, and 4 in Portugal), P. pinaster from 19 sites (2 in Italy, 13 in Spain, and 4 in Portugal), and P. halepensis from 38 sites in Spain. The correlations between IADF frequency and monthly minimum, mean and maximum temperatures, as well as between IADF frequency and total precipitation, were analyzed. A significant negative relationship between IADF frequency and tree-ring age was found for the three Mediterranean pines. Moreover, IADFs were more frequent in wider rings than in narrower ones, although the widest rings showed a reduced IADF frequency. Wet conditions during late summer/early autumn triggered the formation of IADFs in the three species. Our results suggest the existence of a common climatic driver for the formation of IADFs in Mediterranean pines, highlighting the potential use of IADF frequency as a proxy for climate reconstructions with geographical resolution. PMID- 27200053 TI - Moss Pathogenesis-Related-10 Protein Enhances Resistance to Pythium irregulare in Physcomitrella patens and Arabidopsis thaliana. AB - Plants respond to pathogen infection by activating signaling pathways leading to the accumulation of proteins with diverse roles in defense. Here, we addressed the functional role of PpPR-10, a pathogenesis-related (PR)-10 gene, of the moss Physcomitrella patens, in response to biotic stress. PpPR-10 belongs to a multigene family and encodes a protein twice the usual size of PR-10 proteins due to the presence of two Bet v1 domains. Moss PR-10 genes are differentially regulated during development and inoculation with the fungal pathogen Botrytis cinerea. Specifically, PpPR-10 transcript levels increase significantly by treatments with elicitors of Pectobacterium carotovorum subsp. carotovorum, spores of B. cinerea, and the defense hormone salicylic acid. To characterize the role of PpPR-10 in plant defense against pathogens, we conducted overexpression analysis in P. patens and in Arabidopsis thaliana. We demonstrate that constitutive expression of PpPR-10 in moss tissues increased resistance against the oomycete Pythium irregulare. PpPR-10 overexpressing moss plants developed less symptoms and decreased mycelium growth than wild type plants. In addition, PpPR-10 overexpressing plants constitutively produced cell wall depositions in protonemal tissue. Ectopic expression of PpPR-10 in Arabidopsis resulted in increased resistance against P. irregulare as well, evidenced by smaller lesions and less cellular damage compared to wild type plants. These results indicate that PpPR-10 is functionally active in the defense against the pathogen P. irregulare, in both P. patens and Arabidopsis, two evolutionary distant plants. Thus, P. patens can serve as an interesting source of genes to improve resistance against pathogen infection in flowering plants. PMID- 27200054 TI - Brassica napus Genome Possesses Extraordinary High Number of CAMTA Genes and CAMTA3 Contributes to PAMP Triggered Immunity and Resistance to Sclerotinia sclerotiorum. AB - Calmodulin-binding transcription activators (CAMTAs) play important roles in various plant biological processes including disease resistance and abiotic stress tolerance. Oilseed rape (Brassica napus L.) is one of the most important oil-producing crops worldwide. To date, compositon of CAMTAs in genomes of Brassica species and role of CAMTAs in resistance to the devastating necrotrophic fungal pathogen Sclerotinia sclerotiorum are still unknown. In this study, 18 CAMTA genes were identified in oilseed rape genome through bioinformatics analyses, which were inherited from the nine copies each in its progenitors Brassica rapa and Brassica oleracea and represented the highest number of CAMTAs in a given plant species identified so far. Gene structure, protein domain organization and phylogentic analyses showed that the oilseed rape CAMTAs were structurally similar and clustered into three major groups as other plant CAMTAs, but had expanded subgroups CAMTA3 and CAMTA4 genes uniquely in rosids species occurring before formation of oilseed rape. A large number of stress response related cis-elements existed in the 1.5 kb promoter regions of the BnCAMTA genes. BnCAMTA genes were expressed differentially in various organs and in response to treatments with plant hormones and the toxin oxalic acid (OA) secreted by S. sclerotiorum as well as the pathogen inoculation. Remarkably, the expression of BnCAMTA3A1 and BnCAMTA3C1 was drastically induced in early phase of S. sclerotiorum infection, indicating their potential role in the interactions between oilseed rape and S. sclerotiorum. Furthermore, inoculation analyses using Arabidopsis camta mutants demonstrated that Atcamta3 mutant plants exhibited significantly smaller disease lesions than wild-type and other Atcamta mutant plants. In addition, compared with wild-type plants, Atcamta3 plants accumulated obviously more hydrogen peroxide in response to the PAMP chitin and exhibited much higher expression of the CGCG-box-containing genes BAK1 and JIN1, which are essential to the PAMP triggered immunity (PTI) and/or plant resistance to pathogens including S. sclerotiorum. Our results revealed that CAMTA3 negatively regulated PTI probably by directly targeting BAK1 and it also negatively regulated plant defense through suppressing JA signaling pathway probably via directly targeting JIN1. PMID- 27200051 TI - Photoactivation: The Light-Driven Assembly of the Water Oxidation Complex of Photosystem II. AB - Photosynthetic water oxidation is catalyzed by the Mn4CaO5 cluster of photosystem II. The assembly of the Mn4O5Ca requires light and involves a sequential process called photoactivation. This process harnesses the charge-separation of the photochemical reaction center and the coordination environment provided by the amino acid side chains of the protein to oxidize and organize the incoming manganese ions to form the oxo-bridged metal cluster capable of H2O-oxidation. Although most aspects of this assembly process remain poorly understood, recent advances in the elucidation of the crystal structure of the fully assembled cyanobacterial PSII complex help in the interpretation of the rich history of experiments designed to understand this process. Moreover, recent insights on the structure and stability of the constituent ions of the Mn4CaO5 cluster may guide future experiments. Here we consider the literature and suggest possible models of assembly including one involving single Mn(2+) oxidation site for all Mn but requiring ion relocation. PMID- 27200055 TI - Identification of Topping Responsive Proteins in Tobacco Roots. AB - The process of topping elicits many responses in the tobacco plant, including an increase in nicotine biosynthesis, and the secondary growth of roots. Some topping responsive miRNAs and genes have been identified in our previous study, but the mechanism of the tobacco response to topping has not yet been fully elucidated. In this study, topping responsive proteins isolated from tobacco roots were screened using two-dimensional electrophoresis. Of the proteins identified, calreticulin and auxin-responsive protein indole acetic acid (IAA9) were involved in the secondary growth of roots; leucine-rich repeat disease resistance, heat shock protein 70, and farnesyl pyrophosphate synthase 1 were involved in the wounding stress response; and F-box protein played an important role in promoting the ability of nicotine synthesis after topping. In addition, we identified five tobacco bHLH proteins (NtbHLH, NtMYC1a, NtMYC1b, NtMYC2a, and NtMYC2b) related to nicotine biosynthesis. NtMYC2 was suggested to be the main positive transcription factor, with NtbHLH protein being a negative regulator in the jasmonic acid (JA)-mediated activation of nicotine biosynthesis after topping. Tobacco topping activates a comprehensive range of biological processes involving the IAA and JA signaling pathways, and the identification of proteins involved in these processes will improve our understanding of the topping response. PMID- 27200057 TI - Alleviation of Drought Stress and Metabolic Changes in Timothy (Phleum pratense L.) Colonized with Bacillus subtilis B26. AB - Drought is a major limiting factor of crop productivity worldwide and its incidence is predicted to increase under climate change. Drought adaptation of cool-season grasses is thus a major challenge to secure the agricultural productivity under current and future climate conditions. Endophytes are non pathogenic plant-associated bacteria that can play an important role in conferring resistance and improving plant tolerance to drought. In this study, the effect of inoculation of the bacterial endophyte Bacillus subtilis strain B26 on growth, water status, photosynthetic activity and metabolism of timothy (Phleum pratense L.) subjected to drought stress was investigated under controlled conditions. Under both drought-stress and non-stressed conditions, strain B26 successfully colonized the internal tissues of timothy and had a positive impact on plant growth. Exposure of inoculated plant to a 8-week drought stress led to significant increase in shoot and root biomass by 26.6 and 63.8%, and in photosynthesis and stomatal conductance by 55.2 and 214.9% respectively, compared to non-inoculated plants grown under similar conditions. There was a significant effect of the endophyte on plant metabolism; higher levels of several sugars, notably sucrose and fructans and an increase of key amino acids such as, asparagine, glutamic acid and glutamine were recorded in shoots and roots of colonized plants compared to non-colonized ones. The accumulation of the non protein amino acid GABA in shoots of stressed plants and in roots of stressed and unstressed plants was increased in the presence of the endophyte. Taken together, our results indicate that B. subtilis B26 improves timothy growth under drought stress through the modification of osmolyte accumulation in roots and shoots. These results will contribute to the development of a microbial agent to improve the yield of grass species including forage crops and cereals exposed to environmental stresses. PMID- 27200058 TI - Unraveling Aspects of Bacillus amyloliquefaciens Mediated Enhanced Production of Rice under Biotic Stress of Rhizoctonia solani. AB - Rhizoctonia solani is a necrotrophic fungi causing sheath blight in rice leading to substantial loss in yield. Excessive and persistent use of preventive chemicals raises human health and environment safety concerns. As an alternative, use of biocontrol agents is highly recommended. In the present study, an abiotic stress tolerant, plant growth promoting rhizobacteria Bacillus amyloliquefaciens (SN13) is demonstrated to act as a biocontrol agent and enhance immune response against R. solani in rice by modulating various physiological, metabolic, and molecular functions. A sustained tolerance by SN13 primed plant over a longer period of time, post R. solani infection may be attributed to several unconventional aspects of the plants' physiological status. The prolonged stress tolerance observed in presence of SN13 is characterized by (a) involvement of bacterial mycolytic enzymes, (b) sustained maintenance of elicitors to keep the immune system induced involving non-metabolizable sugars such as turanose besides the known elicitors, (c) a delicate balance of ROS and ROS scavengers through production of proline, mannitol, and arabitol and rare sugars like fructopyranose, beta-D-glucopyranose and myoinositol and expression of ferric reductases and hypoxia induced proteins, (d) production of metabolites like quinazoline and expression of terpene synthase, and (e) hormonal cross talk. As the novel aspect of biological control this study highlights the role of rare sugars, maintenance of hypoxic conditions, and sucrose and starch metabolism in B. amyloliquefaciens (SN13) mediated sustained biotic stress tolerance in rice. PMID- 27200059 TI - Divergent Adaptive Strategies by Two Co-occurring Epiphytic Orchids to Water Stress: Escape or Avoidance? AB - Due to the fluctuating water availability in the arboreal habitat, epiphytic plants are considered vulnerable to climate change and anthropogenic disturbances. Although co-occurring taxa have been observed divergent adaptive performances in response to drought, the underlying physiological and morphological mechanisms by which epiphyte species cope with water stress remain poorly understood. In the present study, two co-occurring epiphytic orchids with different phenologies were selected to investigate their drought-resistance performances. We compared their functional traits, and monitored their physiological performances in a 25-days of drought treatment. In contrast to the deciduous species Pleione albiflora, the evergreen species Coelogyne corymbosa had different root anatomical structures and higher values for saturated water content of pseudobulbs. Moreover, plants of C. corymbosa had thicker leaves and epidermis, denser veins and stomata, and higher values for leaf mass per unit area and the time required to dry saturated leaves to 70% relative water content. However, samples from that species had lower values for net photosynthetic rate (A n), stomatal length and chlorophyll content per unit dry mass. Nevertheless, due to greater capacity for water storage and conservation, C. corymbosa maintained higher A n, stomatal conductance (g s), and instantaneous water-use efficiency during severe drought period, and their values for leaf water potential were higher after the water stress treatment. By Day 10 after irrigation was restarted, only C. corymbosa plants recovered their values for A n and g s to levels close to those calculated prior to the imposition of water stress. Our results suggest that the different performance responding to drought and re-watering in two co-occurring epiphytic orchids is related to water-related traits and these two species have divergent adaptive mechanisms. Overall, C. corymbosa demonstrates drought avoidance by enhancing water uptake and storage, and by reducing water losses while P. albiflora employs a drought escape strategy by fixing more carbon during growing season and shedding leaves and roots at dry season, leaving a dormant pseudobulb to minimize transpiration. These findings may improve our understanding of the potential effects that climate change can have on the population dynamics of different epiphytic taxa. PMID- 27200056 TI - Microbe Associated Molecular Pattern Signaling in Guard Cells. AB - Stomata, formed by pairs of guard cells in the epidermis of terrestrial plants, regulate gas exchange, thus playing a critical role in plant growth and stress responses. As natural openings, stomata are exploited by microbes as an entry route. Recent studies reveal that plants close stomata upon guard cell perception of molecular signatures from microbes, microbe associated molecular patterns (MAMPs), to prevent microbe invasion. The perception of MAMPs induces signal transduction including recruitment of second messengers, such as Ca(2+) and H2O2, phosphorylation events, and change of transporter activity, leading to stomatal movement. In the present review, we summarize recent findings in signaling underlying MAMP-induced stomatal movement by comparing with other signalings. PMID- 27200060 TI - Increased Virulence in Sunflower Broomrape (Orobanche cumana Wallr.) Populations from Southern Spain Is Associated with Greater Genetic Diversity. AB - Orobanche cumana Wallr. (sunflower broomrape) is a holoparasitic weed that infects roots of sunflower in large areas of Europe and Asia. Two distant O. cumana gene pools have been identified in Spain, one in Cuenca province in the Center and another one in the Guadalquivir Valley in the South. Race F has been hypothesized to have arisen by separate mutational events in both gene pools. In the Guadalquivir Valley, race F spread in the middle 1990's to become predominant and contained so far with race F hybrids. Recently, enhanced virulent populations of O. cumana have been observed in commercial fields parasitizing race F resistant hybrids. From them, we collected four independent populations and conducted virulence and SSR marker-based genetic diversity analysis. Virulence essays confirmed that the four populations studied can parasitize most of the race F resistant hybrids tested, but they cannot parasitize the differential inbred lines DEB-2, carrying resistance to race F and G, and P-96, resistant to F but susceptible to races G from other countries. Accordingly, the new populations have been classified as race GGV to distinguish them from other races G. Cluster analysis with a set of populations from the two Spanish gene pools and from other areas, mainly Eastern Europe, confirmed that race GGV populations maintain close genetic relatedness with the Guadalquivir Valley gene pool. This suggested that increased virulence was not caused by new introductions from other countries. Genetic diversity parameters revealed that the four populations had much greater genetic diversity than conventional populations of the same area, containing only alleles present in the Guadalquivir Valley and Cuenca gene pools. The results suggested that increased virulence may have resulted from admixture of populations from the Guadalquivir Valley and Cuenca followed by recombination of avirulence genes. PMID- 27200061 TI - Comprehensive Analysis and Expression Profiling of the OsLAX and OsABCB Auxin Transporter Gene Families in Rice (Oryza sativa) under Phytohormone Stimuli and Abiotic Stresses. AB - The plant hormone auxin regulates many aspects of plant growth and developmental processes. Auxin gradient is formed in plant as a result of polar auxin transportation by three types of auxin transporters such as OsLAX, OsPIN, and OsABCB. We report here the analysis of two rice auxin transporter gene families, OsLAX and OsABCB, using bioinformatics tools, publicly accessible microarray data, and quantitative RT-PCR. There are 5 putative OsLAXs and 22 putative OsABCBs in rice genome, which were mapped on 8 chromosomes. The exon-intron structure of OsLAX genes and properties of deduced proteins were relatively conserved within grass family, while that of OsABCB genes varied greatly. Both constitutive and organ/tissue specific expression patterns were observed in OsLAXs and OsABCBs. Analysis of evolutionarily closely related "gene pairs" together with organ/tissue specific expression revealed possible "function gaining" and "function losing" events during rice evolution. Most OsLAX and OsABCB genes were regulated by drought and salt stress, as well as hormonal stimuli [auxin and Abscisic Acid (ABA)], which suggests extensive crosstalk between abiotic stresses and hormone signaling pathways. The existence of large number of auxin and stress related cis-regulatory elements in promoter regions might account for their massive responsiveness of these genes to these environmental stimuli, indicating complexity of regulatory networks involved in various developmental and physiological processes. The comprehensive analysis of OsLAX and OsABCB auxin transporter genes in this study would be helpful for understanding the biological significance of these gene families in hormone signaling and adaptation of rice plants to unfavorable environments. PMID- 27200063 TI - Structure and Function of Intra-Annual Density Fluctuations: Mind the Gaps. AB - Tree rings are natural archives of climate and environmental information with a yearly resolution. Indeed, wood anatomical, chemical, and other properties of tree rings are a synthesis of several intrinsic and external factors, and their interaction during tree growth. In particular, Intra-Annual Density Fluctuations (IADFs) can be considered as tree-ring anomalies that can be used to better understand tree growth and to reconstruct past climate conditions with intra annual resolution. However, the ecophysiological processes behind IADF formation, as well as their functional impact, remain unclear. Are IADFs resulting from a prompt adjustment to fluctuations in environmental conditions to avoid stressful conditions and/or to take advantage from favorable conditions? In this paper we discuss: (1) the influence of climatic factors on the formation of IADFs; (2) the occurrence of IADFs in different species and environments; (3) the potential of new approaches to study IADFs and identify their triggering factors. Our final aim is to underscore the advantages offered by network analyses of data and the importance of high-resolution measurements to gain insight into IADFs formation processes and their relations with climatic conditions, including extreme weather events. PMID- 27200062 TI - The Impact of Competition and Allelopathy on the Trade-Off between Plant Defense and Growth in Two Contrasting Tree Species. AB - In contrast to plant-animal interactions, the conceptual framework regarding the impact of secondary metabolites in mediating plant-plant interference is currently less well defined. Here, we address hypotheses about the role of chemically-mediated plant-plant interference (i.e., allelopathy) as a driver of Mediterranean forest dynamics. Growth and defense abilities of a pioneer (Pinus halepensis) and a late-successional (Quercus pubescens) Mediterranean forest species were evaluated under three different plant interference conditions: (i) allelopathy simulated by application of aqueous needle extracts of Pinus, (ii) resource competition created by the physical presence of a neighboring species (Pinus or Quercus), and (iii) a combination of both allelopathy and competition. After 24 months of experimentation in simulated field conditions, Quercus was more affected by plant interference treatments than was Pinus, and a hierarchical response to biotic interference (allelopathy < competition < allelopathy + competition) was observed in terms of relative impact on growth and plant defense. Both species modulated their respective metabolic profiles according to plant interference treatment and thus their inherent chemical defense status, resulting in a physiological trade-off between plant growth and production of defense metabolites. For Quercus, an increase in secondary metabolite production and a decrease in plant growth were observed in all treatments. In contrast, this trade-off in Pinus was only observed in competition and allelopathy + competition treatments. Although Pinus and Quercus expressed differential responses when subjected to a single interference condition, either allelopathy or competition, species responses were similar or positively correlated when strong interference conditions (allelopathy + competition) were imposed. PMID- 27200064 TI - Identification of a Candidate Gene for Panicle Length in Rice (Oryza sativa L.) Via Association and Linkage Analysis. AB - Panicle length (PL) is an important trait for improving panicle architecture and grain yield in rice (Oryza sativa L.). Three populations were used to identify QTLs and candidate genes associated with PL. Four QTLs for PL were detected on chromosomes 4, 6, and 9 through linkage mapping in the recombinant inbred line population derived from a cross between the cultivars Xiushui79 (short panicle) and C-bao (long panicle). Ten SSR markers associated with PL were detected on chromosomes 2, 3, 5, 6, 8, 9, and 10 in the natural population consisting of 540 accessions collected from East and Southeast Asia. A major locus on chromosome 9 with the largest effect was identified via both linkage and association mapping. LONG PANICLE 1 (LP1) locus was delimited to a 90-kb region of the long arm of chromosome 9 through fine mapping using a single segment segregating F2 population. Two single nucleotide polymorphisms (SNPs) leading to amino acid changes were detected in the third and fifth exons of LP1. LP1 encodes a Remorin_C-containing protein of unknown function with homologs in a variety of species. Sequencing analysis of LP1 in two parents and 103 rice accessions indicated that SNP1 is associated with panicle length. The LP1 allele of Xiushui79 leads to reduced panicle length, whereas the allele of C-bao relieves the suppression of panicle length. LP1 and the elite alleles can be used to improve panicle length in rice. PMID- 27200065 TI - Exogenous Application of Growth Enhancers Mitigate Water Stress in Wheat by Antioxidant Elevation. AB - The present study was conducted to investigate the response of two wheat cultivars (AARI-11 and Millat-11) to a foliar application of four growth enhancers which include: {H2O (water), MLE30 (moringa leaf extract), KCl (potassium chloride), and BAP (benzyl-amino purine)}, within the six irrigation water-regimes which are applied at the various critical growth stages such as crown root initiation (CRI), tillering (T), booting (B), and heading (H). Irrigation water-regimes include: CRI+T+B, CRI+T, CRI+B, T+B, T+H, and control (CRI+T+B+H). The growth enhancers i.e., H2O, MLE30 (1:30), KCl (2%), and BAP (50 mg L(-1)) were applied @ 500 L ha(-1) at tillering and heading stages. The results demonstrated some increased quantities of both enzymatic (superoxide dismutase, peroxidase, catalase) and non-enzymatic (ascorbic acid, phenol) antioxidants in leaves of AARI-11 when MLE30 was applied under T+B and T+H irrigation water-regimes. Similar results were also observed in the case of leaf chlorophyll "a" and "b" and K(+) contents in both cultivars under control, T+B and CRI+T+B irrigation water regimes. AARI-11 produced the highest biological and grain yield, due to the application of MLE30 and BAP under control, CRI+T+B, T+B, and T+H irrigation water-regimes. However, KCl lagged behind among the treatments set for both cultivars under all the irrigation water-regimes. Foliar spray of MLE30 remained prominent growth enhancer and stresses mitigating agent under water deficit conditions particularly under T+B and T+H irrigation water-regimes. Moreover, economic analysis indicated that the foliar application of MLE30 is a cost effective and environment friendly strategy for the maximum yield and income. PMID- 27200067 TI - OsGatB, the Subunit of tRNA-Dependent Amidotransferase, Is Required for Primary Root Development in Rice. AB - A short-root rice mutant was isolated from an ethyl methane sulfonate-mutagenized library. From map-based cloning strategy, a point mutation, resulting in an amino acid change from proline to leucine, was identified in the fourth exon of a glutamyl-tRNA (Gln) amidotransferase B subunit family protein (OsGatB, LOC_Os11g34210). This gene is an ortholog of Arabidopsis GatB and yeast PET112. GatB is a subunit of tRNA-dependent amidotransferase (AdT), an essential enzyme involved in Gln-tRNA(Gln) synthesis in mitochondria. Although previous studies have described that cessation in mitochondrial translation is lethal at very early developmental stages in plants, this point mutation resulted in a non lethal phenotype of smaller root meristem and shorter root cell length. In the root, OsGatB was predominantly expressed in the root tip and played an important role in cell division and elongation there. OsGatB was localized in the mitochondria, and mitochondrial structure and function were all affected in Osgatb root tip cells. PMID- 27200066 TI - Prevalent Exon-Intron Structural Changes in the APETALA1/FRUITFULL, SEPALLATA, AGAMOUS-LIKE6, and FLOWERING LOCUS C MADS-Box Gene Subfamilies Provide New Insights into Their Evolution. AB - AP1/FUL, SEP, AGL6, and FLC subfamily genes play important roles in flower development. The phylogenetic relationships among them, however, have been controversial, which impedes our understanding of the origin and functional divergence of these genes. One possible reason for the controversy may be the problems caused by changes in the exon-intron structure of genes, which, according to recent studies, may generate non-homologous sites and hamper the homology-based sequence alignment. In this study, we first performed exon-by-exon alignments of these and three outgroup subfamilies (SOC1, AG, and STK). Phylogenetic trees reconstructed based on these matrices show improved resolution and better congruence with species phylogeny. In the context of these phylogenies, we traced evolutionary changes of exon-intron structures in each subfamily. We found that structural changes have occurred frequently following gene duplication and speciation events. Notably, exons 7 and 8 (if present) suffered more structural changes than others. With the knowledge of exon-intron structural changes, we generated more reasonable alignments containing all the focal subfamilies. The resulting trees showed that the SEP subfamily is sister to the monophyletic group formed by AP1/FUL and FLC subfamily genes and that the AGL6 subfamily forms a sister group to the three abovementioned subfamilies. Based on this topology, we inferred the evolutionary history of exon-intron structural changes among different subfamilies. Particularly, we found that the eighth exon originated before the divergence of AP1/FUL, FLC, SEP, and AGL6 subfamilies and degenerated in the ancestral FLC-like gene. These results provide new insights into the origin and evolution of the AP1/FUL, FLC, SEP, and AGL6 subfamilies. PMID- 27200068 TI - Common Bean: A Legume Model on the Rise for Unraveling Responses and Adaptations to Iron, Zinc, and Phosphate Deficiencies. AB - Common bean (Phaseolus vulgaris) was domesticated ~8000 years ago in the Americas and today is a staple food worldwide. Besides caloric intake, common bean is also an important source of protein and micronutrients and it is widely appreciated in developing countries for their affordability (compared to animal protein) and its long storage life. As a legume, common bean also has the economic and environmental benefit of associating with nitrogen-fixing bacteria, thus reducing the use of synthetic fertilizers, which is key for sustainable agriculture. Despite significant advances in the plant nutrition field, the mechanisms underlying the adaptation of common bean to low nutrient input remains largely unknown. The recent release of the common bean genome offers, for the first time, the possibility of applying techniques and approaches that have been exclusive to model plants to study the adaptive responses of common bean to challenging environments. In this review, we discuss the hallmarks of common bean domestication and subsequent distribution around the globe. We also discuss recent advances in phosphate, iron, and zinc homeostasis, as these nutrients often limit plant growth, development, and yield. In addition, iron and zinc are major targets of crop biofortification to improve human nutrition. Developing common bean varieties able to thrive under nutrient limiting conditions will have a major impact on human nutrition, particularly in countries where dry beans are the main source of carbohydrates, protein and minerals. PMID- 27200070 TI - Implication of Abscisic Acid on Ripening and Quality in Sweet Cherries: Differential Effects during Pre- and Post-harvest. AB - Sweet cherry, a non-climacteric fruit, is usually cold-stored during post-harvest to prevent over-ripening. The aim of the study was to evaluate the role of abscisic acid (ABA) on fruit growth and ripening of this fruit, considering as well its putative implication in over-ripening and effects on quality. We measured the endogenous concentrations of ABA during the ripening of sweet cherries (Prunus avium L. var. Prime Giant) collected from orchard trees and in cherries exposed to 4 degrees C and 23 degrees C during 10 days of post-harvest. Furthermore, we examined to what extent endogenous ABA concentrations were related to quality parameters, such as fruit biomass, anthocyanin accumulation and levels of vitamins C and E. Endogenous concentrations of ABA in fruits increased progressively during fruit growth and ripening on the tree, to decrease later during post-harvest at 23 degrees C. Cold treatment, however, increased ABA levels and led to an inhibition of over-ripening. Furthermore, ABA levels positively correlated with anthocyanin and vitamin E levels during pre-harvest, but not during post-harvest. We conclude that ABA plays a major role in sweet cherry development, stimulating its ripening process and positively influencing quality parameters during pre-harvest. The possible influence of ABA preventing over-ripening in cold-stored sweet cherries is also discussed. PMID- 27200069 TI - Copper Trafficking in Plants and Its Implication on Cell Wall Dynamics. AB - In plants, copper (Cu) acts as essential cofactor of numerous proteins. While the definitive number of these so-called cuproproteins is unknown, they perform central functions in plant cells. As micronutrient, a minimal amount of Cu is needed to ensure cellular functions. However, Cu excess may exert in contrast detrimental effects on plant primary production and even survival. Therefore it is essential for a plant to have a strictly controlled Cu homeostasis, an equilibrium that is both tissue and developmentally influenced. In the current review an overview is presented on the different stages of Cu transport from the soil into the plant and throughout the different plant tissues. Special emphasis is on the Cu-dependent responses mediated by the SPL7 transcription factor, and the crosstalk between this transcriptional regulation and microRNA-mediated suppression of translation of seemingly non-essential cuproproteins. Since Cu is an essential player in electron transport, we also review the recent insights into the molecular mechanisms controlling chloroplastic and mitochondrial Cu transport and homeostasis. We finally highlight the involvement of numerous Cu proteins and Cu-dependent activities in the properties of one of the major Cu accumulation sites in plants: the cell wall. PMID- 27200071 TI - Biomass Allocation of Stoloniferous and Rhizomatous Plant in Response to Resource Availability: A Phylogenetic Meta-Analysis. AB - Resource allocation to different functions is central in life-history theory. Plasticity of functional traits allows clonal plants to regulate their resource allocation to meet changing environments. In this study, biomass allocation traits of clonal plants were categorized into absolute biomass for vegetative growth vs. for reproduction, and their relative ratios based on a data set including 115 species and derived from 139 published literatures. We examined general pattern of biomass allocation of clonal plants in response to availabilities of resource (e.g., light, nutrients, and water) using phylogenetic meta-analysis. We also tested whether the pattern differed among clonal organ types (stolon vs. rhizome). Overall, we found that stoloniferous plants were more sensitive to light intensity than rhizomatous plants, preferentially allocating biomass to vegetative growth, aboveground part and clonal reproduction under shaded conditions. Under nutrient- and water-poor condition, rhizomatous plants were constrained more by ontogeny than by resource availability, preferentially allocating biomass to belowground part. Biomass allocation between belowground and aboveground part of clonal plants generally supported the optimal allocation theory. No general pattern of trade-off was found between growth and reproduction, and neither between sexual and clonal reproduction. Using phylogenetic meta-analysis can avoid possible confounding effects of phylogeny on the results. Our results shown the optimal allocation theory explained a general trend, which the clonal plants are able to plastically regulate their biomass allocation, to cope with changing resource availability, at least in stoloniferous and rhizomatous plants. PMID- 27200072 TI - The Role of Slr0151, a Tetratricopeptide Repeat Protein from Synechocystis sp. PCC 6803, during Photosystem II Assembly and Repair. AB - The assembly and repair of photosystem II (PSII) is facilitated by a variety of assembly factors. Among those, the tetratricopeptide repeat (TPR) protein Slr0151 from Synechocystis sp. PCC 6803 (hereafter Synechocystis) has previously been assigned a repair function under high light conditions (Yang et al., 2014). Here, we show that inactivation of slr0151 affects thylakoid membrane ultrastructure even under normal light conditions. Moreover, the level and localization of Slr0151 are affected in a variety of PSII-related mutants. In particular, the data suggest a close functional relationship between Slr0151 and Sll0933, which interacts with Ycf48 during PSII assembly and is homologous to PAM68 in Arabidopsis thaliana. Immunofluorescence analysis revealed a punctate distribution of Slr0151 within several different membrane types in Synechocystis cells. PMID- 27200074 TI - Erratum: Non-targeted Metabolite Profiling and Scavenging Activity Unveil the Nutraceutical Potential of Psyllium (Plantago ovata Forsk). AB - [This corrects the article on p. 431 in vol. 7, PMID: 27092153.]. PMID- 27200073 TI - Dissecting miRNAs in Wheat D Genome Progenitor, Aegilops tauschii. AB - As the post-transcriptional regulators of gene expression, microRNAs or miRNAs comprise an integral part of understanding how genomes function. Although miRNAs have been a major focus of recent efforts, miRNA research is still in its infancy in most plant species. Aegilops tauschii, the D genome progenitor of bread wheat, is a wild diploid grass exhibiting remarkable population diversity. Due to the direct ancestry and the diverse gene pool, A. tauschii is a promising source for bread wheat improvement. In this study, a total of 87 Aegilops miRNA families, including 51 previously unknown, were computationally identified both at the subgenomic level, using flow-sorted A. tauschii 5D chromosome, and at the whole genome level. Predictions at the genomic and subgenomic levels suggested A. tauschii 5D chromosome as rich in pre-miRNAs that are highly associated with Class II DNA transposons. In order to gain insights into miRNA evolution, putative 5D chromosome miRNAs were compared to its modern ortholog, Triticum aestivum 5D chromosome, revealing that 48 of the 58 A. tauschii 5D miRNAs were conserved in orthologous T. aestivum 5D chromosome. The expression profiles of selected miRNAs (miR167, miR5205, miR5175, miR5523) provided the first experimental evidence for miR5175, miR5205 and miR5523, and revealed differential expressional changes in response to drought in different genetic backgrounds for miR167 and miR5175. Interestingly, while miR5523 coding regions were present and expressed as pre-miR5523 in both T. aestivum and A. tauschii, the expression of mature miR5523 was observed only in A. tauschii under normal conditions, pointing out to an interference at the downstream processing of pre-miR5523 in T. aestivum. Overall, this study expands our knowledge on the miRNA catalog of A. tauschii, locating a subset specifically to the 5D chromosome, with ample functional and comparative insight which should contribute to and complement efforts to develop drought tolerant wheat varieties. PMID- 27200075 TI - Epigenetic Characterization of CDKN1C in Placenta Samples from Non-syndromic Intrauterine Growth Restriction. AB - The cyclin-dependent kinase (CDK)-inhibitor 1C (CDKN1C) gene is expressed from the maternal allele and is located within the centromeric imprinted domain at chromosome 11p15. It is a negative regulator of proliferation, with loss-of function mutations associated with the overgrowth disorder Beckwith-Wiedemann syndrome. Recently, gain-of-function mutations within the PCNA domain have been described in two disorders characterized by growth failure, namely IMAGe (intra uterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita and genital abnormalities) syndrome and Silver-Russell syndrome (SRS). Over expression of CDKN1C by maternally inherited microduplications also results in SRS, suggesting that in addition to activating mutations this gene may regulate growth by changes in dosage. To determine if CDKN1C is involved in non-syndromic IUGR we compared the expression and DNA methylation levels in a large cohort of placental biopsies from IUGR and uneventful pregnancies. We observe higher levels of expression of CDKN1C in IUGR placentas compared to those of controls. All placenta biopsies heterozygous for the PAPA repeat sequence in exon 2 showed appropriate monoallelic expression and no mutations in the PCNA domain were observed. The expression profile was independent of both genetic or methylation variation in the minimal CDKN1C promoter interval and of methylation of the cis acting maternally methylated region associated with the neighboring KCNQ1OT1 non coding RNA. Chromatin immunoprecipitation revealed binding sites for CTCF within the unmethylated CDKN1C gene body CpG island and putative enhancer regions, associated with the canonical enhancer histone signature, H3K4me1 and H3K27ac, located ~58 and 360 kb away. Using 3C-PCR we identify constitutive higher-order chromatin loops that occur between one of these putative enhancer regions and CDKN1C in human placenta tissues, which we propose facilitates expression. PMID- 27200077 TI - Editorial: DNA and RNA Metabolism Meet at Chromatin to Control Genome Stability. PMID- 27200076 TI - The Evolving Diagnostic and Genetic Landscapes of Autism Spectrum Disorder. AB - The autism spectrum disorders (ASD) are a heterogeneous set of neurodevelopmental syndromes defined by impairments in verbal and non-verbal communication, restricted social interaction, and the presence of stereotyped patterns of behavior. The prevalence of ASD is rising, and the diagnostic criteria and clinical perspectives on the disorder continue to evolve in parallel. Although the majority of individuals with ASD will not have an identifiable genetic cause, almost 25% of cases have identifiable causative DNA variants. The rapidly improving ability to identify genetic mutations because of advances in next generation sequencing, coupled with previous epidemiological studies demonstrating high heritability of ASD, have led to many recent attempts to identify causative genetic mutations underlying the ASD phenotype. However, although hundreds of mutations have been identified to date, they are either rare variants affecting only a handful of ASD patients, or are common variants in the general population conferring only a small risk for ASD. Furthermore, the genes implicated thus far are heterogeneous in their structure and function, hampering attempts to understand shared molecular mechanisms among all ASD patients; an understanding that is crucial for the development of targeted diagnostics and therapies. However, new work is beginning to suggest that the heterogeneous set of genes implicated in ASD may ultimately converge on a few common pathways. In this review, we discuss the parallel evolution of our diagnostic and genetic understanding of autism spectrum disorders, and highlight recent attempts to infer common biology underlying this complicated syndrome. PMID- 27200079 TI - Editorial: Improving Animal Welfare through Genetic Selection. PMID- 27200080 TI - Evaluation of BRCAPRO Risk Assessment Model in Patients with Ductal Carcinoma In situ Who Underwent Clinical BRCA Genetic Testing. AB - The authors retrospectively aimed to determine which of the following three scenarios, related to DCIS entry into BRCAPRO, predicted BRCA mutation status more accurately: (1) DCIS as an invasive breast cancer (IBC) entered using the actual age of diagnosis, (2) DCIS as IBC entered with 10 years added to the actual age of diagnosis, and (3) DCIS entered as no cancer. Of the 85 DCIS patients included in the study, 19% (n = 16) tested positive for a BRCA mutation, and 81% (n = 69) tested negative. DCIS patients who tested positive for a BRCA mutation had a higher BRCAPRO risk estimation (34.61%) than patients who tested negative (11.4%) when DCIS was entered at the actual age of diagnosis. When DCIS was entered with 10 years added to the actual age at diagnosis, the BRCAPRO estimate was still higher amongst BRCA positive patients (25.4%) than BRCA negative patients (7.1%). When DCIS was entered as no cancer, the BRCAPRO estimate remained higher among BRCA positive patients (2.56%) than BRCA negative patents (1.98%). In terms of accuracy of BRCA positivity, there was no statistically significant difference between DCIS at age at diagnosis, DCIS at 10 years later than age at diagnosis, and DCIS entered as no cancer (AUC = 0.77, 0.784, 0.75, respectively: p = 0.60). Our results indicate that regardless of entry approach into BRCAPRO, there were no significant differences in predicting BRCA mutation in patients with DCIS. PMID- 27200078 TI - Global-genome Nucleotide Excision Repair Controlled by Ubiquitin/Sumo Modifiers. AB - Global-genome nucleotide excision repair (GG-NER) prevents genome instability by excising a wide range of different DNA base adducts and crosslinks induced by chemical carcinogens, ultraviolet (UV) light or intracellular side products of metabolism. As a versatile damage sensor, xeroderma pigmentosum group C (XPC) protein initiates this generic defense reaction by locating the damage and recruiting the subunits of a large lesion demarcation complex that, in turn, triggers the excision of aberrant DNA by endonucleases. In the very special case of a DNA repair response to UV radiation, the function of this XPC initiator is tightly controlled by the dual action of cullin-type CRL4(DDB2) and sumo-targeted RNF111 ubiquitin ligases. This twofold protein ubiquitination system promotes GG NER reactions by spatially and temporally regulating the interaction of XPC protein with damaged DNA across the nucleosome landscape of chromatin. In the absence of either CRL4(DDB2) or RNF111, the DNA excision repair of UV lesions is inefficient, indicating that these two ubiquitin ligases play a critical role in mitigating the adverse biological effects of UV light in the exposed skin. PMID- 27200081 TI - Genes with a Combination of Over-Dominant and Epistatic Effects Underlie Heterosis in Growth of Saccharomyces cerevisiae at High Temperature. AB - Heterosis describes a phenotypic phenomenon of hybrid superiority over its homozygous parents. It is a genetically intriguing phenomenon with great importance for food production. Also called hybrid-vigor, heterosis is created by non-additive effects of genes in a heterozygous hybrid made by crossing two distinct homozygous parents. Few models have been proposed to explain how the combination of parental genes creates an exceptional hybrid performance. Over dominant mode of inheritance is an attractive model since a single gene can potentially create the heterotic effect, but only a few such loci have been identified. To a collection of 120 hybrids, made by crossing 16 divergent Saccharomyces cerevisiae yeast strains, we applied a method for mapping heterozygous loci that non-additively contribute to heterotic growth at 37 degrees . Among 803 candidate loci that were mapped, five were tested for their heterotic effect by analyzing backcrosses and F2 populations in a specific hybrid background. Consistently with the many mapped loci, specific analyses confirmed the minor heterotic effect of the tested candidate loci. Allele-replacement analyses of one gene, AEP3, further supported its heterotic effect. In addition to over-dominant effects, the contribution of epistasis to heterosis was evident from F2 population and allele-replacement analyses. Pairs of over-dominant genes contributed synergistically to heterosis. We show that minor over-dominant effects of multiple genes can combine to condition heterosis, similarly to loci affecting other quantitative traits. Furthermore, by finding of epistatic interactions between loci that each of them individually has an over-dominant effect on heterosis, we demonstrate how hybrid advantage could benefit from a synergistic combination of two interaction types (over-dominant and synergistic epistatic). Thus, by portraying the underlying genetic complexity, these findings advance our understanding of heterosis. PMID- 27200083 TI - Current Approaches Toward Quantitative Mapping of the Interactome. AB - Protein-protein interactions (PPIs) play a key role in many, if not all, cellular processes. Disease is often caused by perturbation of PPIs, as recently indicated by studies of missense mutations. To understand the associations of proteins and to unravel the global picture of PPIs in the cell, different experimental detection techniques for PPIs have been established. Genetic and biochemical methods such as the yeast two-hybrid system or affinity purification-based approaches are well suited to high-throughput, proteome-wide screening and are mainly used to obtain qualitative results. However, they have been criticized for not reflecting the cellular situation or the dynamic nature of PPIs. In this review, we provide an overview of various genetic methods that go beyond qualitative detection and allow quantitative measuring of PPIs in mammalian cells, such as dual luminescence-based co-immunoprecipitation, Forster resonance energy transfer or luminescence-based mammalian interactome mapping with bait control. We discuss the strengths and weaknesses of different techniques and their potential applications in biomedical research. PMID- 27200084 TI - Integrated Systems for NGS Data Management and Analysis: Open Issues and Available Solutions. AB - Next-generation sequencing (NGS) technologies have deeply changed our understanding of cellular processes by delivering an astonishing amount of data at affordable prices; nowadays, many biology laboratories have already accumulated a large number of sequenced samples. However, managing and analyzing these data poses new challenges, which may easily be underestimated by research groups devoid of IT and quantitative skills. In this perspective, we identify five issues that should be carefully addressed by research groups approaching NGS technologies. In particular, the five key issues to be considered concern: (1) adopting a laboratory management system (LIMS) and safeguard the resulting raw data structure in downstream analyses; (2) monitoring the flow of the data and standardizing input and output directories and file names, even when multiple analysis protocols are used on the same data; (3) ensuring complete traceability of the analysis performed; (4) enabling non-experienced users to run analyses through a graphical user interface (GUI) acting as a front-end for the pipelines; (5) relying on standard metadata to annotate the datasets, and when possible using controlled vocabularies, ideally derived from biomedical ontologies. Finally, we discuss the currently available tools in the light of these issues, and we introduce HTS-flow, a new workflow management system conceived to address the concerns we raised. HTS-flow is able to retrieve information from a LIMS database, manages data analyses through a simple GUI, outputs data in standard locations and allows the complete traceability of datasets, accompanying metadata and analysis scripts. PMID- 27200086 TI - Editorial: Gene Targeting in Neuroscience: Entering the Future. PMID- 27200082 TI - Ring of Change: CDC48/p97 Drives Protein Dynamics at Chromatin. AB - The dynamic composition of proteins associated with nuclear DNA is a fundamental property of chromosome biology. In the chromatin compartment dedicated protein complexes govern the accurate synthesis and repair of the genomic information and define the state of DNA compaction in vital cellular processes such as chromosome segregation or transcription. Unscheduled or faulty association of protein complexes with DNA has detrimental consequences on genome integrity. Consequently, the association of protein complexes with DNA is remarkably dynamic and can respond rapidly to cellular signaling events, which requires tight spatiotemporal control. In this context, the ring-like AAA+ ATPase CDC48/p97 emerges as a key regulator of protein complexes that are marked with ubiquitin or SUMO. Mechanistically, CDC48/p97 functions as a segregase facilitating the extraction of substrate proteins from the chromatin. As such, CDC48/p97 drives molecular reactions either by directed disassembly or rearrangement of chromatin bound protein complexes. The importance of this mechanism is reflected by human pathologies linked to p97 mutations, including neurodegenerative disorders, oncogenesis, and premature aging. This review focuses on the recent insights into molecular mechanisms that determine CDC48/p97 function in the chromatin environment, which is particularly relevant for cancer and aging research. PMID- 27200085 TI - Population Stratification in the Context of Diverse Epidemiologic Surveys Sans Genome-Wide Data. AB - Population stratification or confounding by genetic ancestry is a potential cause of false associations in genetic association studies. Estimation of and adjustment for genetic ancestry has become common practice thanks in part to the availability of ancestry informative markers on genome-wide association study (GWAS) arrays. While array data is now widespread, these data are not ubiquitous as several large epidemiologic and clinic-based studies lack genome-wide data. One such large epidemiologic-based study lacking genome-wide data accessible to investigators is the National Health and Nutrition Examination Surveys (NHANES), population-based cross-sectional surveys of Americans linked to demographic, health, and lifestyle data conducted by the Centers for Disease Control and Prevention. DNA samples (n = 14,998) were extracted from biospecimens from consented NHANES participants between 1991-1994 (NHANES III, phase 2) and 1999 2002 and represent three major self-identified racial/ethnic groups: non-Hispanic whites (n = 6,634), non-Hispanic blacks (n = 3,458), and Mexican Americans (n = 3,950). We as the Epidemiologic Architecture for Genes Linked to Environment study genotyped candidate gene and GWAS-identified index variants in NHANES as part of the larger Population Architecture using Genomics and Epidemiology I study for collaborative genetic association studies. To enable basic quality control such as estimation of genetic ancestry to control for population stratification in NHANES san genome-wide data, we outline here strategies that use limited genetic data to identify the markers optimal for characterizing genetic ancestry. From among 411 and 295 autosomal SNPs available in NHANES III and NHANES 1999-2002, we demonstrate that markers with ancestry information can be identified to estimate global ancestry. Despite limited resolution, global genetic ancestry is highly correlated with self-identified race for the majority of participants, although less so for ethnicity. Overall, the strategies outlined here for a large epidemiologic study can be applied to other datasets accessible for genotype-phenotype studies but are sans genome-wide data. PMID- 27200087 TI - Cartography of Pathway Signal Perturbations Identifies Distinct Molecular Pathomechanisms in Malignant and Chronic Lung Diseases. AB - Lung diseases are described by a wide variety of developmental mechanisms and clinical manifestations. Accurate classification and diagnosis of lung diseases are the bases for development of effective treatments. While extensive studies are conducted toward characterization of various lung diseases at molecular level, no systematic approach has been developed so far. Here we have applied a methodology for pathway-centered mining of high throughput gene expression data to describe a wide range of lung diseases in the light of shared and specific pathway activity profiles. We have applied an algorithm combining a Pathway Signal Flow (PSF) algorithm for estimation of pathway activity deregulation states in lung diseases and malignancies, and a Self Organizing Maps algorithm for classification and clustering of the pathway activity profiles. The analysis results allowed clearly distinguish between cancer and non-cancer lung diseases. Lung cancers were characterized by pathways implicated in cell proliferation, metabolism, while non-malignant lung diseases were characterized by deregulations in pathways involved in immune/inflammatory response and fibrotic tissue remodeling. In contrast to lung malignancies, chronic lung diseases had relatively heterogeneous pathway deregulation profiles. We identified three groups of interstitial lung diseases and showed that the development of characteristic pathological processes, such as fibrosis, can be initiated by deregulations in different signaling pathways. In conclusion, this paper describes the pathobiology of lung diseases from systems viewpoint using pathway centered high-dimensional data mining approach. Our results contribute largely to current understanding of pathological events in lung cancers and non-malignant lung diseases. Moreover, this paper provides new insight into molecular mechanisms of a number of interstitial lung diseases that have been studied to a lesser extent. PMID- 27200089 TI - Knowledge and Informed Decision-Making about Population-Based Colorectal Cancer Screening Participation in Groups with Low and Adequate Health Literacy. AB - Objective. To analyze and compare decision-relevant knowledge, decisional conflict, and informed decision-making about colorectal cancer (CRC) screening participation between potential screening participants with low and adequate health literacy (HL), defined as the skills to access, understand, and apply information to make informed decisions about health. Methods. Survey including 71 individuals with low HL and 70 with adequate HL, all eligible for the Dutch organized CRC screening program. Knowledge, attitude, intention to participate, and decisional conflict were assessed after reading the standard information materials. HL was assessed using the Short Assessment of Health Literacy in Dutch. Informed decision-making was analyzed by the multidimensional measure of informed choice. Results. 64% of the study population had adequate knowledge of CRC and CRC screening (low HL 43/71 (61%), adequate HL 47/70 (67%), p > 0.05). 57% were informed decision-makers (low HL 34/71 (55%), adequate HL 39/70 (58%), p > 0.05). Intention to participate was 89% (low HL 63/71 (89%), adequate HL 63/70 (90%)). Respondents with low HL experienced significantly more decisional conflict (25.8 versus 16.1; p = 0.00). Conclusion. Informed decision-making about CRC screening participation was suboptimal among both individuals with low HL and individuals with adequate HL. Further research is required to develop and implement effective strategies to convey decision-relevant knowledge about CRC screening to all screening invitees. PMID- 27200088 TI - Anchoring a Leviathan: How the Nuclear Membrane Tethers the Genome. AB - It is well established that the nuclear envelope has many distinct direct connections to chromatin that contribute to genome organization. The functional consequences of genome organization on gene regulation are less clear. Even less understood is how interactions of lamins and nuclear envelope transmembrane proteins (NETs) with chromatin can produce anchoring tethers that can withstand the physical forces of and on the genome. Chromosomes are the largest molecules in the cell, making megadalton protein structures like the nuclear pore complexes and ribosomes seem small by comparison. Thus to withstand strong forces from chromosome dynamics an anchoring tether is likely to be much more complex than a single protein-protein or protein-DNA interaction. Here we will briefly review known NE-genome interactions that likely contribute to spatial genome organization, postulate in the context of experimental data how these anchoring tethers contribute to gene regulation, and posit several hypotheses for the physical nature of these tethers that need to be investigated experimentally. Significantly, disruption of these anchoring tethers and the subsequent consequences for gene regulation could explain how mutations in nuclear envelope proteins cause diseases ranging from muscular dystrophy to lipodystrophy to premature aging progeroid syndromes. The two favored hypotheses for nuclear envelope protein involvement in disease are (1) weakening nuclear and cellular mechanical stability, and (2) disrupting genome organization and gene regulation. Considerable experimental support has been obtained for both. The integration of both mechanical and gene expression defects in the disruption of anchoring tethers could provide a unifying hypothesis consistent with both. PMID- 27200090 TI - 11beta-Hydroxysteroid Dehydrogenase 2 in Preeclampsia. AB - Preeclampsia is a serious medical problem affecting the mother and her child and influences their health not only during the pregnancy, but also many years after. Although preeclampsia is a subject of many research projects, the etiology of the condition remains unclear. One of the hypotheses related to the etiology of preeclampsia is the deficiency in placental 11beta-hydroxysteroid dehydrogenase 2 (11beta-HSD2), the enzyme which in normal pregnancy protects the fetus from the excess of maternal cortisol. The reduced activity of the enzyme was observed in placentas from pregnancies complicated with preeclampsia. That suggests the overexposure of the developing child to maternal cortisol, which in high levels exerts proapoptotic effects and reduces fetal growth. The fetal growth restriction due to the diminished placental 11beta-HSD2 function may be supported by the fact that preeclampsia is often accompanied with fetal hypotrophy. The causes of the reduced function of 11beta-HSD2 in placental tissue are still discussed. This paper summarizes the phenomena that may affect the activity of the enzyme at various steps on the way from the gene to the protein. PMID- 27200091 TI - Developing a Suitable Model for Water Uptake for Biodegradable Polymers Using Small Training Sets. AB - Prediction of the dynamic properties of water uptake across polymer libraries can accelerate polymer selection for a specific application. We first built semiempirical models using Artificial Neural Networks and all water uptake data, as individual input. These models give very good correlations (R (2) > 0.78 for test set) but very low accuracy on cross-validation sets (less than 19% of experimental points within experimental error). Instead, using consolidated parameters like equilibrium water uptake a good model is obtained (R (2) = 0.78 for test set), with accurate predictions for 50% of tested polymers. The semiempirical model was applied to the 56-polymer library of L-tyrosine-derived polyarylates, identifying groups of polymers that are likely to satisfy design criteria for water uptake. This research demonstrates that a surrogate modeling effort can reduce the number of polymers that must be synthesized and characterized to identify an appropriate polymer that meets certain performance criteria. PMID- 27200092 TI - Oxidative Nanopatterning of Titanium Surface Influences mRNA and MicroRNA Expression in Human Alveolar Bone Osteoblastic Cells. AB - Titanium implants have been extensively used in orthopedic and dental applications. It is well known that micro- and nanoscale surface features of biomaterials affect cellular events that control implant-host tissue interactions. To improve our understanding of how multiscale surface features affect cell behavior, we used microarrays to evaluate the transcriptional profile of osteoblastic cells from human alveolar bone cultured on engineered titanium surfaces, exhibiting the following topographies: nanotexture (N), nano+submicrotexture (NS), and rough microtexture (MR), obtained by modulating experimental parameters (temperature and solution composition) of a simple yet efficient chemical treatment with a H2SO4/H2O2 solution. Biochemical assays showed that cell culture proliferation augmented after 10 days, and cell viability increased gradually over 14 days. Among the treated surfaces, we observed an increase of alkaline phosphatase activity as a function of the surface texture, with higher activity shown by cells adhering onto nanotextured surfaces. Nevertheless, the rough microtexture group showed higher amounts of calcium than nanotextured group. Microarray data showed differential expression of 716 mRNAs and 32 microRNAs with functions associated with osteogenesis. Results suggest that oxidative nanopatterning of titanium surfaces induces changes in the metabolism of osteoblastic cells and contribute to the explanation of the mechanisms that control cell responses to micro- and nanoengineered surfaces. PMID- 27200093 TI - Antimicrobial Evaluation of Bacterial Isolates from Urine Specimen of Patients with Complaints of Urinary Tract Infections in Awka, Nigeria. AB - Urinary tract infections (UTIs) account for one of the major reasons for most hospital visits and the determination of the antimicrobial susceptibility patterns of uropathogens will help to guide physicians on the best choice of antibiotics to recommend to affected patients. This study is designed to isolate, characterize, and determine the antimicrobial susceptibility patterns of the pathogens associated with UTI in Anambra State Teaching Hospital, Amaku, Anambra State, Nigeria. Clean catch urine samples of inpatient and outpatient cases of UTI were collected and bacteriologically analyzed using standard microbiological procedures. Antibiogram was done by the Kirby-Bauer disc diffusion method. The most prevalent isolates were S. aureus (28%), E. coli (24.6%), and S. saprophyticus (20%). The antibacterial activities of the tested agents were in the order of Augmentin < Ceftazidime < Cefuroxime < Cefixime < Gentamicin < Ofloxacin < Ciprofloxacin < Nitrofurantoin. It was found that all the organisms were susceptible in varying degrees to Nitrofurantoin, Ciprofloxacin, and Ofloxacin. It was also observed that all the bacterial species except Streptococcus spp. have a Multiple Antibiotic Resistance Index (MARI) greater than 0.2. For empiric treatment of UTIs in Awka locality, Nitrofurantoin, Ciprofloxacin, and Ofloxacin are the first line of choice. PMID- 27200094 TI - SAPHIRE: Stress and Pulmonary Hypertension in Rheumatoid Evaluation-A Prevalence Study. AB - Pulmonary artery hypertension (PAH) is a disorder of elevated resistance in the pulmonary arterial vessels, reflected by elevation of measured pulmonary artery pressure (PAP), and presenting with breathlessness and, if untreated, progressing to right heart failure and death. The heightened prevalence of PAH in populations with underlying systemic autoimmune conditions, particularly scleroderma and its variants, is well recognised, consistent with the proposed autoimmune contribution to PAH pathogenesis, along with disordered thrombotic, inflammatory, and mitogenic factors. Rheumatoid arthritis (RA) is one of a group of systemic autoimmune conditions featuring inflammatory symmetrical erosive polyarthropathy as its hallmark. This study explored the prevalence of PAH in a population of unselected individuals with RA, using exercise echocardiography (EchoCG). The high prevalence of EchoCG-derived elevation of PAP (EDEPP) in this population (14%) suggests that, like other autoimmune conditions, RA may be a risk factor for PAH. Patients with RA may therefore represent another population for whom PAH screening with noninvasive tools such as EchoCG may be justified. PMID- 27200095 TI - Bronchiolitis Obliterans Organizing Pneumonia as an Initial Presentation of Systemic Lupus Erythematosus: A Rare Case Report and Literature Review. AB - The etiology of bronchiolitis obliterans organizing pneumonia (BOOP) remains controversial. While it has been reportedly associated with several connective tissue disorders, there are only rare reports of BOOP associated with systemic lupus erythematosus (SLE). Herein, we report a 56-year-old female patient who presented with dyspnea on exertion, cough, fever, and joint pain of her left wrist and fingers as initial symptoms. Laboratory tests revealed positivity for anti-nuclear antibody, anti-Ro, and anti-double strand DNA antibody. In this case, the patient with SLE had respiratory illness as the initial symptom due to BOOP in the absence of clear etiology. The diagnosis of BOOP was confirmed by thoracic surgery biopsy. Her respiratory symptoms and radiologic findings significantly improved following prednisolone treatment. PMID- 27200097 TI - The In Vitro and In Vivo Wound Healing Properties of the Chinese Herbal Medicine "Jinchuang Ointment". AB - "Jinchuang ointment" is a traditional Chinese herbal medicine complex for treatment of incised wounds. For more than ten years, it has been used at China Medical University Hospital (Taichung, Taiwan) for the treatment of diabetic foot infections and decubitus ulcers. Three different cases are presented in this study. "Jinchuang" ointment is a mixture of natural product complexes from nine different components, making it difficult to analyze its exact chemical compositions. To further characterize the herbal ingredients used in this study, the contents of reference standards present in a subset of the ointment ingredients (dragon's blood, catechu, frankincense, and myrrh) were determined by HPLC. Two in vitro cell based assay platforms, wound healing and tube formation, were used to examine the biological activity of this medicine. Our results show that this herbal medicine possesses strong activities including stimulation of angiogenesis, cell proliferation, and cell migration, which provide the scientific basis for its clinically observed curative effects on nonhealing diabetic wounds. PMID- 27200098 TI - Study on the Mechanism Underlying the Regulation of the NMDA Receptor Pathway in Spinal Dorsal Horns of Visceral Hypersensitivity Rats by Moxibustion. AB - Visceral hypersensitivity is enhanced in irritable bowel syndrome (IBS) patients. Treatment of IBS visceral pain by moxibustion methods has a long history and rich clinical experience. In the clinic, moxibustion on the Tianshu (ST25) and Shangjuxu (ST37) acupoints can effectively treat bowel disease with visceral pain and diarrhea symptoms. To investigate the regulatory function of moxibustion on the Tianshu (ST25) and Shangjuxu (ST37) acupoints on spinal cord NR1, NR2B, and PKCepsilon protein and mRNA expression in irritable bowel syndrome (IBS) visceral hypersensitivity rats, we did some research. In the study, we found that moxibustion effectively relieved the IBS visceral hyperalgesia status of rats. Analgesic effect of moxibustion was similar to intrathecal injection of Ro 25 6981. The expression of NR1, NR2B, and PKCepsilon in the spinal dorsal horns of IBS visceral hyperalgesia rats increased. Moxibustion on the Tianshu and Shangjuxu acupoints might inhibit the visceral hypersensitivity, simultaneously decreasing the expression of NR1, NR2B, and PKCepsilon in spinal cord of IBS visceral hyperalgesia rats. Based on the above experimental results, we hypothesized NR1, NR2B, and PKCepsilon of spinal cord could play an important role in moxibustion inhibiting the process of central sensitization and visceral hyperalgesia state. PMID- 27200099 TI - Acute and Subchronic Oral Toxicity Evaluation of Aqueous Root Extract of Dicoma anomala Sond. in Wistar Rats. AB - The present study evaluated the safety of aqueous root extract of Dicoma anomala (AQRED) through acute and subchronic toxicity studies. Single oral dose of AQRED at the concentration of 0, 5, 300, and 2000 mg/kg as well as 125, 250, and 500 mg/kg/day was administered to rats for 14-day acute and 90-day subchronic oral toxicity studies. The results revealed no mortalities or observed clinical signs of toxicity in all the rats during both investigation periods. In subchronic toxicity testing, administration of AQRED also did not cause any changes in body weight as well as food and water consumption patterns. The haematological parameters and blood chemistry revealed no significant difference (p > 0.05) between the treatment and the control except in platelet count, alkaline phosphatase, and sodium levels where there was a significant increase (p < 0.05), although there was also a significant reduction (p < 0.05) in alanine transaminase, aspartate transaminase, and creatinine when compared to control. However, these changes were not reflecting the results from histology. Conclusively, the obtained results suggested that the LD50 of AQRED is in excess of 2000 mg/kg and its oral administration for 90 days revealed that it is unlikely to be toxic, hence, safe. PMID- 27200096 TI - The Importance of CD44 as a Stem Cell Biomarker and Therapeutic Target in Cancer. AB - CD44 is a cell surface HA-binding glycoprotein that is overexpressed to some extent by almost all tumors of epithelial origin and plays an important role in tumor initiation and metastasis. CD44 is a compelling marker for cancer stem cells of many solid malignancies. In addition, interaction of HA and CD44 promotes EGFR-mediated pathways, consequently leading to tumor cell growth, tumor cell migration, and chemotherapy resistance in solid cancers. Accumulating evidence indicates that major HA-CD44 signaling pathways involve a specific variant of CD44 isoforms; however, the particular variant almost certainly depends on the type of tumor cell and the stage of the cancer progression. Research to date suggests use of monoclonal antibodies against different CD44 variant isoforms and targeted inhibition of HA/CD44-mediated signaling combined with conventional radio/chemotherapy may be the most favorable therapeutic strategy for future treatments of advanced stage malignancies. Thus, this paper briefly focuses on the association of the major CD44 variant isoforms in cancer progression, the role of HA-CD44 interaction in oncogenic pathways, and strategies to target CD44-overexpressed tumor cells. PMID- 27200100 TI - Traditional Therapies Used to Manage Diabetes and Related Complications in Mauritius: A Comparative Ethnoreligious Study. AB - Religious communities from Mauritius still rely on traditional therapies (TT) for primary healthcare. Nonetheless, there is still a dearth of scientific information on TT used by the different religious groups to manage diabetes and related complications (DRC). This study aimed to gather ethnomedicinal knowledge on TT used by the different religious groups against DRC. Diabetic patients (n = 95) and traditional healers (n = 5) were interviewed. Fifty-two plant species belonging to 33 families and 26 polyherbal formulations were documented to manage DRC. The most reported DRC was hypertension (n = 36). Leaves (45.2%) and juice (36%) were the most cited mode of preparation of herbal recipes. Plants which scored high relative frequency of citation were Citrus aurantifolia (0.55) and Morinda citrifolia (0.54). The cultural importance index showed that Ocimum tenuiflorum, Cardiospermum halicacabum, Camellia sinensis, and Ophiopogon japonicas were the most culturally important plants among Hindu, Muslim, Christian, and Buddhist community, respectively. Hindu and Muslim community showed the highest similarity of medicinal plants usage (Jaccard index = 95.8). Seven animal species distributed over 4 classes were recorded for the management of DRC. Plants and animals recorded as TT should be submitted to scientific studies to confirm safety and efficacy in clinical practice and to identify pharmacologically active metabolites. PMID- 27200101 TI - Shengmai San Ameliorates Myocardial Dysfunction and Fibrosis in Diabetic db/db Mice. AB - In this study, we mainly investigated the effects of Shengmai San (SMS) on diabetic cardiomyopathy (DCM) in db/db mice. The db/db mice were randomly divided into model group and SMS group, while C57BLKS/J inbred mice were used as controls. After 24-week treatment, blood glucose, body weight, and heart weight were determined. Hemodynamic changes in the left ventricle were measured using catheterization. The myocardial structure and subcellular structural changes were observed by HE staining and electron microscopy; the myocardium collagen content was quantified by Masson staining. To further explore the protective mechanism of SMS, we analyzed the expression profiles of fibrotic related proteins. Compared to nondiabetic mice, db/db mice exhibited enhanced diastolic myocardial dysfunction and adverse structural remodeling. Higher expression of profibrotic proteins and lower levels of extracellular matrix degradation were also observed. After SMS oral administration for 24 weeks, cardiac dysfunction, hypertrophy, and fibrosis in diabetic mice were greatly improved. Moreover, increased profibrotic protein expression was strongly reversed by SMS treatment in db/db mice. The results demonstrate that SMS exerts a cardioprotective effect against DCM by attenuating myocardial hypertrophy and fibrosis via a TGF-beta dependent pathway. PMID- 27200102 TI - Inhibitory Effects of Angelica Polysaccharide on Activation of Mast Cells. AB - This study was designed to investigate the inhibitory effects of Angelica polysaccharide (AP) on activation of mast cells and its possible molecular mechanism. In our study, we determined the proinflammatory cytokines and allergic mediators in anti-DNP IgE stimulated RBL-2H3 cells and found that AP (50, 100, and 200 MUg/mL) significantly decreased the release of histamine, beta hexosaminidase, leukotrienes C4 (LTC4), IL-1, IL-4, TNF-alpha, IL-6, and human monocyte chemotactic protein-1 (MCP-1/CCL2) (p < 0.05). In addition, Ca(2+) entry was inhibited by treatment with AP. AP also downregulated the protein expressions of p-Fyn, p-Akt, p-P38, IL-4, TNF-alpha, and NF-kappaB p65 in both Fyn gene upregulated and normal RBL-2H3 cells (p < 0.05). Collectively, our results showed that AP could inhibit the activation of mast cells via suppressing the releases of proinflammatory cytokines allergic mediators, Gab2/PI3-K/Akt and Fyn/Syk pathways. PMID- 27200103 TI - A Fomitopsis pinicola Jeseng Formulation Has an Antiobesity Effect and Protects against Hepatic Steatosis in Mice with High-Fat Diet-Induced Obesity. AB - This study investigated the antiobesity effect of an extract of the Fomitopsis pinicola Jeseng-containing formulation (FAVA), which is a combination of four natural components: Fomitopsis pinicola Jeseng; Acanthopanax senticosus; Viscum album coloratum; and Allium tuberosum. High-fat diet- (HFD-) fed male C57BL/6J mice were treated with FAVA (200 mg/kg/day) for 12 weeks to monitor the antiobesity effect and amelioration of nonalcoholic fatty liver diseases (NAFLD). Body and white adipose tissue (WAT) weights were reduced in FAVA-treated mice, and a histological examination showed an amelioration of fatty liver in FAVA treated mice without decreasing food consumption. Additionally, FAVA reduced serum lipid profiles, leptin, and insulin levels compared with the HFD control group. The FAVA extract suppressed lipogenic mRNA expression levels from WAT concomitantly with the cholesterol biosynthesis level in the liver. These results demonstrate the inhibitory effects of FAVA on obesity and NAFLD in the diet induced obese (DIO) mouse model. Therefore, FAVA may be an effective therapeutic candidate for treating obesity and fatty liver caused by a high-fat diet. PMID- 27200105 TI - The Classification of Sini Decoction Pattern in Traditional Chinese Medicine by Gene Expression Profiling. AB - We investigated the syndromes of the Sini decoction pattern (SDP), a common ZHENG in traditional Chinese medicine (TCM). The syndromes of SDP were correlated with various severe Yang deficiency related symptoms. To obtain a common profile for SDP, we distributed questionnaires to 300 senior clinical TCM practitioners. According to the survey, we concluded 2 sets of symptoms for SDP: (1) pulse feels deep or faint and (2) reversal cold of the extremities. Twenty-four individuals from Taipei City Hospital, Linsen Chinese Medicine Branch, Taiwan, were recruited. We extracted the total mRNA of peripheral blood mononuclear cells from the 24 individuals for microarray experiments. Twelve individuals (including 6 SDP patients and 6 non-SDP individuals) were used as the training set to identify biomarkers for distinguishing the SDP and non-SDP groups. The remaining 12 individuals were used as the test set. The test results indicated that the gene expression profiles of the identified biomarkers could effectively distinguish the 2 groups by adopting a hierarchical clustering algorithm. Our results suggest the feasibility of using the identified biomarkers in facilitating the diagnosis of TCM ZHENGs. Furthermore, the gene expression profiles of biomarker genes could provide a molecular explanation corresponding to the ZHENG of TCM. PMID- 27200106 TI - Hopes, Dreams and Anxieties: India's One-Child Families. AB - While rapid fertility decline in India in the last two decades has received considerable attention, much of the discourse has focused on a decline in high parity births. However, this paper finds that, almost hidden from the public gaze, a small but significant segment of the Indian population has begun the transition to extremely low fertility. Among the urban, upper income, educated, middle classes, it is no longer unusual to find families stopping at one child, even when this child is a girl. Using data from the India Human Development Survey of 2004-2005, we examine the factors that may lead some families to stop at a single child. We conclude that the motivations for this very low fertility are likely to be a more extreme form of those for low fertility rather than reflecting the qualitative change in ideologies and worldviews that is hypothesized to accompany very low fertility during the second demographic transition. PMID- 27200107 TI - Association of peripheral BDNF level with cognition, attention and behavior in preschool children. AB - BACKGROUND: Brain-derived neurotrophic factor (BDNF) has been reported to affect development, cognition, attention and behavior. However, few studies have investigated preschool children with regard to these areas. We evaluated the relationship between cognition, attention and peripheral blood concentration of BDNF in preschool children. METHODS: Twenty-eight children (mean age: 6.16 +/- 0.60 years) were recruited. For all subjects, serum and plasma BDNF levels were assessed; intelligence was assessed using the Korean standardisation of the Wechsler Intelligence Scale for Children (KEDI-WISC); attention was assessed using the computerised continuous performance test (CCPT), the children's color trails test (CCTT), the Stroop color-word test for preschool children, and the attention-deficit/hyperactivity disorder rating scale (K-ARS); and finally emotional and behavioral problems were assessed using the child behavior checklist (K-CBCL). We confirmed the previously reported correlations between the various psychometric properties assessed and serum and plasma levels of BDNF in our sample. RESULTS: Serum BDNF levels were negatively correlated with both KEDI WISC full scale IQ (FSIQ, r = -0.39, p = 0.04) and verbal IQ (VIQ, r = -0.05, p = 0.01), but not with the performance IQ (PIQ, r = -0.12, p = 0.56). There were no significant relationships between plasma BDNF level and VIQ, PIQ or FSIQ. No correlations were found between either serum or plasma level of BDNF and any of the attentional measures (CCPT, ARS, CCTT or Stroop color word test). The CBCL total behavioral problem and attention problem sections were positively correlated with plasma BDNF level (r = 0.41, p = 0.03), (r = 0.44, p = 0.02), however, no relationship was found between the serum BDNF and any of the composite CBCL measures. CONCLUSIONS: Our results suggest that high peripheral BDNF may be negatively correlated with intelligence, behavioral problems and clinical symptoms of neuro-developmental disorders such as intellectual disability in preschool children. A high peripheral BDNF concentration may, if these findings are further replicated, prove to be a useful biomarker for such issues in preschool children. PMID- 27200104 TI - The Genus Phyllanthus: An Ethnopharmacological, Phytochemical, and Pharmacological Review. AB - The plants of the genus Phyllanthus (Euphorbiaceae) have been used as traditional medicinal materials for a long time in China, India, Brazil, and the Southeast Asian countries. They can be used for the treatment of digestive disease, jaundice, and renal calculus. This review discusses the ethnopharmacological, phytochemical, and pharmacological studies of Phyllanthus over the past few decades. More than 510 compounds have been isolated, the majority of which are lignins, triterpenoids, flavonoids, and tannins. The researches of their remarkable antiviral, antioxidant, antidiabetic, and anticancer activities have become hot topics. More pharmacological screenings and phytochemical investigations are required to support the traditional uses and develop leading compounds. PMID- 27200108 TI - CE-UV/VIS and CE-MS for monitoring organic impurities during the downstream processing of fermentative-produced lactic acid from second-generation renewable feedstocks. AB - BACKGROUND: During the downstream process of bio-based bulk chemicals, organic impurities, mostly residues from the fermentation process, must be separated to obtain a pure and ready-to-market chemical. In this study, capillary electrophoresis was investigated for the non-targeting downstream process monitoring of organic impurities and simultaneous quantitative detection of lactic acid during the purification process of fermentatively produced lactic acid. The downstream process incorporated 11 separation units, ranging from filtration, adsorption and ion exchange to electrodialysis and distillation, and 15 different second-generation renewable feedstocks were processed into lactic acid. The identification of organic impurities was established through spiking and the utilization of an advanced capillary electrophoresis mass spectrometry system. RESULTS: A total of 53 % of the organic impurities were efficiently removed via bipolar electrodialysis; however, one impurity, pyroglutamic acid, was recalcitrant to separation. It was demonstrated that the presence of pyroglutamic acid disrupts the polymerization of lactic acid into poly lactic acid. Pyroglutamic acid was present in all lactic acid solutions, independent of the type of renewable resource or the bacterium applied. Pyroglutamic acid, also known as 5-oxoproline, is a metabolite in the glutathione cycle, which is present in all living microorganisms. pyroglutamic acid is found in many proteins, and during intracellular protein metabolism, N-terminal glutamic acid and glutamine residues can spontaneously cyclize to become pyroglutamic acid. Hence, the concentration of pyroglutamic acid in the lactic acid solution can only be limited to a certain amount. CONCLUSIONS: The present study proved the capillary electrophoresis system to be an important tool for downstream process monitoring. The high product concentration encountered in biological production processes did not hinder the capillary electrophoresis from separating and detecting organic impurities, even at minor concentrations. The coupling of the capillary electrophoresis with a mass spectrometry system allowed for the straightforward identification of the remaining critical impurity, pyroglutamic acid. Although 11 separation units were applied during the downstream process, the pyroglutamic acid concentration remained at 12,900 ppm, which was comparatively high. All organic impurities found were tracked by the capillary electrophoresis, allowing for further separation optimization. PMID- 27200110 TI - Mindful attention reduces linguistic intergroup bias. AB - A brief mindfulness intervention diminished bias in favor of one's in-group and against one's out-group. In the linguistic intergroup bias (LIB), individuals expect in-group members to behave positively, and out-group members to behave negatively. Consequently, individuals choose abstract language beset with character inferences to describe these expected behaviors, and in contrast, choose concrete, objective language to describe unexpected behaviors. Eighty-four participants received either mindful attention instructions (observe their thoughts as fleeting mental states) or immersion instructions (become absorbed in the vivid details of thoughts). After instruction, participants viewed visual depictions of an imagined in-group or out-group member's positive or negative behavior, selecting the best linguistic description from a set of four descriptions that varied in abstractness. Immersion groups demonstrated a robust LIB. Mindful attention groups, however, exhibited a markedly tempered LIB, suggesting that even a brief mindfulness-related instruction can implicitly reduce the propensity to perpetuate stereotypical thinking through language. These results contribute to understanding the mechanisms that facilitate unprejudiced thinking. PMID- 27200109 TI - Mindfulness-Based Interventions for Older Adults: A Review of the Effects on Physical and Emotional Well-being. AB - This comprehensive review examined the effects of mindfulness-based interventions on the physical and emotional wellbeing of older adults, a rapidly growing segment of the general population. Search procedures yielded 15 treatment outcome studies meeting inclusion criteria. Support was found for the feasibility and acceptability of mindfulness-based interventions with older adults. Physical and emotional wellbeing outcome variables offered mixed support for the use of mindfulness-based interventions with older adults. Potential explanations of mixed findings may include methodological flaws, study limitations, and inconsistent modifications of protocols. These are discussed in detail and future avenues of research are discussed, emphasizing the need to incorporate geriatric populations into future mindfulness-based empirical research. PMID- 27200111 TI - [Accidental intra-oesophageal ingestion of a button]. PMID- 27200112 TI - TSH secreting adenoma: a rare cause of severe headache. PMID- 27200113 TI - [Brain popcorn image]. PMID- 27200114 TI - [Budd-Chiari syndrome: a rare complication of hepatic sarcoidosis (about one case)]. AB - Sarcoidotic involvement of the liver is frequent, albeit uncommonly symptomatic. Anicteric cholestasis and portal hypertension are the main complications. Budd Chiari syndrome is a little known and exceptional complication of hepatic sarcoidosis. We present a case of A 45-year-old woman suffering from hepatic sarcoidosis who developed Budd-Chiari syndrome. PMID- 27200115 TI - [Periprosthetic hip fracture type C Vancouver, what not to do]. PMID- 27200116 TI - [Synovial chondromatosis of the wrist revealed by a carpal tunnel syndrome, an exceptional case]. PMID- 27200117 TI - [Retroperitoneal cystic collection revealing a huge urinoma]. PMID- 27200118 TI - Rhomboid glossitis caused by Candida? PMID- 27200119 TI - Muscular visualisation on a bone scan in paraneoplastic dermatomyositis associated with breast cancer. PMID- 27200120 TI - Dermoscopy in atypical phthiriais eyelash. PMID- 27200121 TI - Isolation and characterization of Escherichia coli pathotypes and factors associated with well and boreholes water contamination in Mombasa County. AB - INTRODUCTION: Safe water for human consumption is important, but there is a limited supply. Mombasa County has water shortages making residences rely on other sources of water including boreholes and wells. Microbiological evaluation of drinking water is important to reduce exposure to water borne enteric diseases. This cross sectional study aimed at determining the frequency and characterization of Escherichia coli (E. coli) pathotypes from water samples collected from wells and boreholes in Mombasa County. METHODS: One hundred and fifty seven (157) water samples were collected from four divisions of the county and a questionnaire administered. The samples were inoculated to double strength MacConkey broth and incubated at 370C for up to 48 hours. Positive results were compared to the 3 tube McCrady MPN table. The E. coli were confirmed by Eijkman's test and antibiotic susceptibility carried out. Using polymerase chain reaction (PCR), the E. coli were characterized to establish pathotypes. RESULTS: One hundred and thirty one (n = 131; 83.4%) samples had coliform bacteria with only 79 (60.3%) samples having E. coli. Significant values (<0.05) were noted when coliforms were compared to variables with E. Coli showing no significance when compared to similar variables. E. coli (n = 77; 100%) tested were sensitive to Gentamicin, while all (n = 77; 100%) isolates were resistant to Ampicillin. PCR typed isolates as enteroinvasive E. Coli (EIEC). CONCLUSION: Findings suggest that coliforms and E. coli are major contaminants of wells and boreholes in Mombasa County. The isolates have a variety of resistant and sensitivity patterns to commonly used antibiotics. PMID- 27200122 TI - [Bilateral temporo mandibular dislocation occurred during eclampsia]. PMID- 27200123 TI - Mucormycosis in a surgical defect masquerading as osteomyelitis: a case report and review of literature. AB - Mucormycosis is a rare, highly lethal opportunistic fungal disease affecting immune compromised and diabetic patients. Mucormycosis is considered as the 3(rd) most common invasive mycosis after candidiasis and aspergillosis in debilitating patients. It is caused by the filamentous fungi of the class zygomycetes. The infection usually begins in the nose due to inhalation of fungal spores. This fatal fungal disease needs a prompt and early definitive diagnosis, aggressive surgical therapy and high dose anti-fungal therapy. Here, we present a case report of Mucormycosis in a 64 year elderly diabetic male patient who was previously operated for myiasis and also the extensive review of the literature of the mucormycosis. PMID- 27200124 TI - [Successive ectopic pregnancies associated with tubal shistosomiasis in a French traveler]. AB - Schistosomiasis is the second endemic parasitic disease in the world and is a common cause of urogenital infections. Ectopic pregnancies due to tubal obstruction by schistosoma's eggs are usually reported in Africa. Schistosomiasis also affects travelers but infection of the female genital tract is less frequently described. We report an unusual clinical case of two successive ectopic pregnancies with tubal schistosomiasis in a French woman, seven years after a travel to Mali. The first event was discovered after histologic examination of salpingectomy and the second event required a controlateral salpingotomy with an injection of methotrexate, two months later. PMID- 27200125 TI - Metabolic syndrome in urban city of North-Western Nigeria: prevalence and determinants. AB - INTRODUCTION: The aim of this study was to investigate the prevalence of metabolic syndrome in Sokoto metropolis of North-Western Nigeria. METHODS: A cross-sectional community based study was carried out. Four hundred and ten subjects (201 males and 209 females) were recruited for the study using a multi stage sampling technique. Demographic and the life style data was obtained from the participants. Evaluation of anthropometric variables, fasting blood sugar, lipid profiles, insulin resistance and blood pressure was performed. The classification of metabolic syndrome was based on the NCEP ATP III guidelines. RESULTS: The mean (SD) age of the sample population was 39.6 (14.4) years. The mean (SD) age of the male subjects was 38.4(14.9) years and that of the females was 40.8(13.9) years (p> 0.05). The overall prevalence of metabolic syndrome was 35.1% with the females having 42.83% and the males 27.36%. The frequencies of metabolic syndrome parameters in the study subjects were low HDL (56.1%), hypertension (46.1%), dysglycemia (32.7%), central obesity (28%), and elevated triglycerides (22.4%). Most of the women had low HDL (62.2%) and central obesity elevated (49.8%). CONCLUSION: Metabolic syndrome is common in residents of North Western Nigeria, commoner in the females than males. Risk factors for metabolic syndrome should be detected in normal individuals for implementing effective preventive measures. PMID- 27200127 TI - The current status of dental graduates in India. AB - The dental profession is a noble profession. It takes years of devotion towards the subject of dentistry to get the graduate degree of Bachelor of Dental Surgery. However, even after such painstaking efforts the current situation of dental graduates in India is grave. There are a lot of issues that are the main cause for this problem. The dental graduates are in a state of crisis due to lack of support from the Government. If this situation continues it will lead to a negative effect on the integrity of the dental profession, and highly trained dental manpower of the country will go in vain. PMID- 27200128 TI - [Pure radio carpal dislocation: a case report]. PMID- 27200126 TI - The when and how of male circumcision and the risk of HIV: a retrospective cross sectional analysis of two HIV surveys from Guinea-Bissau. AB - INTRODUCTION: Male circumcision (MC) reduces the risk of HIV, and this risk reduction may be modified by socio-cultural factors such as the timing and method (medical and traditional) of circumcision. Understanding regional variations in circumcision practices and their relationship to HIV is crucial and can increase insight into the HIV epidemic in Africa. METHODS: We used data from two retrospective HIV surveys conducted in Guinea-Bissau from 1993 to 1996 (1996 cohort) and from 2004 to 2007 (2006 cohort). Multivariate logistical models were used to investigate the relationships between HIV risk and circumcision status, timing, method of circumcision, and socio-demographic factors. RESULTS: MC was protective against HIV infection in both cohorts, with adjusted odds ratios (AORs) of 0.28 (95% CI 0.12-0.66) and 0.30 (95% CI 0.09-0.93), respectively. We observed that post-pubertal (>= 13 years) circumcision provided the highest level of HIV risk reduction in both cohorts compared to non-circumcised. However, the difference between pre-pubertal (<= 12 years) and post-pubertal (>= 13 years) circumcision was not significant in the multivariate analysis. Seventy-six percent (678/888) of circumcised males in the 2006 cohort were circumcised traditionally, and 7.7% of those males were HIV-infected compared to 1.9% of males circumcised medically, with AOR of 2.7 (95% CI 0.91-8.12). CONCLUSION: MC is highly prevalent in Guinea-Bissau, but ethnic variations in method and timing may affect its protection against HIV. Our findings suggest that sexual risk behaviour and traditional circumcision may increases HIV risk. The relationship between circumcision age, sexual behaviour and HIV status remains unclear and warrants further research. PMID- 27200129 TI - [Endoscopic contribution in the dilatation of caustic esophagus stenosis]. AB - INTRODUCTION: The aim of this work was to present the contribution of the endoscopy in the management of esophageal dilatation for caustic esophageal stenosis (CES). METHODS: This was a descriptive and prospective study in the thoracic surgery department at the Hospital of Mali. A total of 46 cases of CES is recorded and divided into 4 groups according to the topography of the esophageal lesions. For the different methods of dilatation the number of performed endoscopic support was determined to understand the contribution of endoscopic means in the success of dilatation for CES. The outcome, complications and mortality in the two methods were compared. RESULTS: Fibroscopy was used in 41.30% of patients with Savary Guillard dilators and in 47.82% of patients with Lerut dilators. Video laryngoscopy was used in 58.69% of patients who underwent dilatation with Lerut dilators. The passage of the guide wire was performed in 39.13% under video laryngoscopy and 58.68% under fibroscopy. In comparison of the two methods, there is a significant difference in the occurrence of complications (p=0.04075), general anesthesia (p=0.02287), accessibility (p=0.04805) and mortality (p=0.00402). CONCLUSION: The CES is a serious disease and under evaluated in Mali. The endoscopies contribute significantly to the success of esophageal dilatation for caustic stenosis in the different methods we used. PMID- 27200130 TI - Food plants used during traditional wrestling in Kabye land of Togo. AB - INTRODUCTION: In the traditional sports like the fight, natural products from minerals, animals and plants are used to increase physical resistance and performance. For a better understanding of this practice, an ethnopharmacological survey was carried out in kabye land, North of Togo, to identify current plants used as foods plants during traditional wrestling. METHODS: Ethnopharmacological data were collected through semi-structured method and personal interviews in the Kabye locality during traditional wrestling. At least, twelve villages were surveyed in the study. RESULTS: Results indicated that 57 plants are widely used by local people as food plants generally during wrestling time. These plants are used traditionally for many others purposes. CONCLUSION: We concluded that these plants may serve as sources for pharmacological investigations in physical performance improvement. PMID- 27200131 TI - Magnitude and correlates of moderate to severe anemia among adult HIV patients receiving first line HAART in Northwestern Tanzania: a cross sectional clinic based study. AB - INTRODUCTION: Moderate to severe anemia is an important clinical problem in HIV patients on Highly Active Antiretroviral Therapy. The rate of progression and mortality in this sub group of patients is high compared to non anemic patients. In sub Saharan Africa with scale up of Anti retroviral therapy, the magnitude of this problem is not known especially in Tanzania. This study aimed at determining the magnitude and correlates of moderate to severe anemia in HIV patients receiving first line ART in northwestern Tanzania. METHODS: This was a cross sectional clinic based study, involving adult HIV patients on first line Highly Active Antiretroviral Therapy at Bugando Medical Centre Care and Treatment Center. The patients' data were analyzed using STATA version 11 to determine the prevalence of moderate to severe anemia and risk factors that could predict occurrence of anemia. RESULTS: In this study 346 patients on Highly Active Anti Retroviral Therapy were enrolled, of whom 100(40.46%) had moderate to severe anemia. The odds of being anemic were strongly predicted by Zidovudine based regime, low baseline CD4 count (< 200 cells/MUl) and HIV stage 3&4 at enrollment. Most of the anemic patients had mean corpuscular volume of >100 fl. CONCLUSION: The prevalence of moderate to severe anemia is significantly high in this cohort of HIV-infected patients on first line Anti Retroviral Therapy and it is strongly predicted by Zidovudine based regime, low baseline CD4 and HIV stage 3 and 4. On clinical grounds this suggests that patients who are initiated on Zidovudine based regimen and those in advanced HIV at enrollment should have regular haemoglobin follow up to identify anemia at its earliest stage to improve the clinical outcome of these patients. PMID- 27200132 TI - Antithyroid drug induced a granulocytosis: what still we need to learn? AB - Antithyroid drugs (ATDs) induced agranulocytosis is a rare but life threatening condition. We report a 29 years Filipino female diagnosed as having hyperthyroidism with normal base line blood counts, liver and renal profile. She was started on maximum 60 mg (20mg TID) oral dose of carbimazole since one month by her treating physician. Exactly after one month of treatment she presented to emergency room (ER) with fever, sore throat and generalized weakness for several days. PMID- 27200133 TI - [Helicobacter pylori gastritis: assessment of OLGA and OLGIM staging systems]. AB - Helicobacter pylori (H pylori) gastritis presents a risk of cancer related to atrophy and intestinal metaplasia. Two recent classifications OLGA (Operative Link on Gastritis Assessment) and OLGIM (Operative Link on Gastritic Intestinal Metaplasia assessment) have been proposed to identify high-risk forms (stages III and IV). The aim of this study is to evaluate the OLGA and OLGIM staging systems in H pylori gastritis. A descriptive study of 100 cases of chronic H pylori gastritis was performed. The revaluation of Sydney System parameters of atrophy and intestinal metaplasia, of gastric antrum and corpus, allowed identifying respectively the stages of OLGA and OLGIM systems. The progressive risk of our H pylori gastritis was 6% according to OLGA staging and 7% according to OLGIM staging. Significant correlation was revealed between age and OLGA staging. High risk gastritis according to OLGIM staging was significantly associated with moderate to severe atrophy. High-risk forms according to OLGA staging were associated in 80% of the cases to intestinal metaplasia. OLGA and OLGIM systems showed a highly significant positive correlation between them with a mismatch at 5% for H pylori gastritis. The OLGA and OLGIM staging systems in addition to Sydney System, allow selection of high risk forms of chronic gastritis requiring accurate observation. PMID- 27200134 TI - Sero-epidemiological survey and risk factors associated with brucellosis in dogs in south-western Nigeria. AB - INTRODUCTION: In Nigeria, there is limited information on brucellosis particularly in dogs, despite its public health implications. We undertook a sero epidemiological survey of brucellosis in dogs to determine the prevalence of the disease and associated risk factors for its occurrence in Nigeria. METHODS: A cross-sectional study was conducted to screen dogs in south-western Nigeria for antibodies to Brucella sp using the rapid slide agglutination test (RSA) and Rose Bengal test (RBT), with positive samples confirmed respectively by serum agglutination test (SAT) and competitive enzyme linked immunosorbent assay (cELISA). Data were analyzed with STATA-12. RESULTS: From the 739 dog sera tested, 81 (10.96%) were positive by RSA and 94 (12.72%) by RBT; these were corroborated with SAT (4/81; 4.94%) and cELISA (1/94; 1.06%), respectively. Logistic regression identified location (OR=0.04; 95% CI: 0.02-0.09), breed (OR=1.71; 95% CI: 1.34-2.19), age (OR=0.10; 95% CI: 0.04-0.30) and management system (OR=8.51; 95% CI: 1.07-68.05) as risk factors for Brucella infection by RSA. However, location (OR=10.83; 95% CI: 5.48-21.39) and history of infertility (OR=2.62; 95% CI: 1.41-4.84) were identified as risk factors using RBT. CONCLUSION: Given the 10.96% to 12.72% seroprevalence of brucellosis recorded in this study, we advocate control of the disease in dogs, and public health education for those at risk of infection. Again, further studies are required to elucidate the role of dogs in the epidemiology of brucellosis in Nigeria considering the conducive human-animal interface and ecological factors responsible for the transmission of the disease. PMID- 27200136 TI - Brain metastasis from male breast cancer treated 12 years ago. PMID- 27200135 TI - [Safety evaluation of anticancer drugs circuit in a regional hospital in Tunisia]. AB - INTRODUCTION: Nowadays, the circuit of drugs is a plague. This situation may cause serious harm to patients. In this context, we conducted a study with the aim to describe and evaluate the circuit of anticancer drugs in a Tunisian regional hospital. METHODS: This is an evaluative study of the risk of anticancer drugs, conducted over a period of 15 days during the year 2014 in the Department of Cancer Research of the Regional Hospital of Gafsa (Tunisia). The evaluation method is based on that conducted by the project "SECURIMED" and developed by the Coordination Committee of the Clinical Evaluation and Quality in Aquitaine (CCECQA) in France. RESULTS: In our study, the observation of anticancer drugs circuit has revealed some deficiencies. We noted that the roles of the various actors are subject sometimes to tasks shifting, which may sometimes be dangerous. The study also revealed a lack and an inadequacy with the standards in terms of the necessary equipment for the preparation of the anticancer drugs. CONCLUSION: Securing drugs circuit should be a priority included in all national processes and shared by all stakeholders to achieve a premium goal: the quality of care and patient safety. PMID- 27200137 TI - [Scooter accidents in children at Aristide Le Dantec, Unversity Hospital of Dakar: a study of 74 cases]. AB - INTRODUCTION: Scooter accidents are becoming more frequent in Dakar. The purpose of this study is to report the epidemiological and lesional aspects of these accidents on children in Dakar. MATERIALS AND METHODS: A retrospective and descriptive study was conducted in Pediatric Surgery Unit of the Aristide Le Dantec Hospital in Dakar from January 1st, 2009 to December 31, 2011. Various parameters were studied. These parameters include: frequency, sociodemographic and lesional aspects. RESULTS: Scooter accidents represent 12% of highway accidents. They were more frequent in the day, from 12 am to 2 pm (27%) and in the night, from 6 pm to 8 pm (28.4%). They might occur every day but were more frequent during April (17.6%) and June (13.5%). They occurred mainly in the suburban district of Dakar (78%). The age group most affected was the one from 3 to 8 years (60.8%). Male gender was predominant (sex ratio 1.5). Pedestrians are the most vulnerable (93.2%). The fall was the dominant mechanism (98.7%). Lesions affected mainly the lower limb (51.1%) and were essentially constituted by fracture. CONCLUSION: The frequency of scooter accidents in children is related to the galloping urbanization and to the increase of the number of cars on the roads in the peninsula. Victims are essentially pedestrians and present most of the time fractures. PMID- 27200138 TI - Psoriasis and Staphylococcus aureus skin colonization in Moroccan patients. AB - Psoriatic lesions are rarely complicated by recurrent infections. The aim of our study is to determine skin colonisation and nasal carriage of Staphylococcus aureus in patients with psoriasis and in healthy persons. PATIENTS AND METHODS: a comparative study that include 33 patients with psoriasis and 33 healthy persons. Samples were taken from lesional and non lesional psoriatic skin and from healthy skin of control group. For S. aureus nasal carriage, we used sterile cotton tipped swabs. Out of 165 samples (66 skin samples and 33 nasal swabs), 26 S. Aureus strains were isolated in 26 persons, 57.69% in the control group and 42.3% in the psoriasis group. S. aureus skin colonization was found in one case (3%) in lesional psoriatic skin vs 9 cases (27.3%) in control skin OR=0.08 IC 95% (0.01 0.70) p=0.02 and in 12,1% in non lesional psoriatic skin vs 27, 3% in control skin (p =0,13). This colonization was less important in lesional psoriatic skin (3%) than in non lesional psoriatic skin (12.1%) p= 0.20. Nasal screening identified (7/33) 21, 21% S. aureus carriers in psoriasis group and in control group. Our results are in consensus with literature findings. They have confirmed the importance of antimicrobial peptides in Innate immunity of human skin. These peptides are normally produced by keratinocytes in response to inflammatory stimuli such as psoriasis. Their high expression in psoriasis skin reduces the risk of skin infection and skin colonization with S. Aureus. PMID- 27200139 TI - An acute adrenal insufficiency revealing pituitary metastases of lung cancer in an elderly patient. AB - Metastases of solid tumors to the pituitary gland are often asymptomatic or appereas as with diabetes insipid us. Pituitary metastases more commonly affect the posterior lobe and the infundibulum than the anterior lobe. The presentation with an acute adrenal insufficiency is a rare event. A 69-year-old men presented with vomiting, low blood pressure and hypoglycemia. Hormonal exploration confirmed a hypopituitarism. Appropriate therapy was initiated urgently. The hypothalamic-pituitary MRI showed a pituitary hypertrophy, a nodular thickening of the pituitary stalk. The chest X Rays revealed pulmonary opacity. Computed tomography scan of the chest showed a multiples tumors with mediastinal lymphadenopathy. Bronchoscopy and biopsy demonstrated a pulmonary adenocarcinoma. Hence we concluded to a lung cancer with multiple pituitary and adrenal gland metastases. This case emphasizes the need for an etiological investigation of acute adrenal insufficiency after treatment of acute phase. PMID- 27200141 TI - [Intracranial multiple aneurysms]. PMID- 27200140 TI - Plastibell circumcision of 2,276 male infants: a multi-centre study. AB - INTRODUCTION: The World Health Organization's manual on male circumcision listed Plastibell technique as a well-proven paediatric method with respect to the results and complications. Although, literatures abound on its wide acceptability, there are few multi-centered reports from this environment. The objective was to evaluate the cases of infant circumcision by Plastibell device from two medical institutions. METHODS: All consecutive infants who had Classical Plastibell Circumcision (PC) at the Federal Staff Medical Centre, Abuja and the Lagos State University Teaching Hospital, Ikeja between February 2011 and June 2015 were included in this cross-sectional study. The procedures were performed by surgical registrars and medical officers after ninety minutes of topical anesthesia to the penis. Data harvested from the standard proforma were analysed using Statistical Package for Social Science 20.0 for window. RESULTS: A total of 2,276 infants had classical PC within the study period. Their ages at circumcision ranged from 4 days to 3 months with a mean age of 17 days. Majority of the boys were circumcised at second week of life (n=1,394,61.2%). All the cases were performed for religious (53%) and cultural (47%)reasons. The most common Plastibell size deployed was 1.3 cm (n=1,040, 45.7%) while 1.6 cm was the least commonly used ring (n=10, 0.4%). The mean time for device to fall-off was 6 days (range 4-12 days). There was no correlation between the age at circumcision and Plastibell size. We recorded an overall complication rate of 1.1% with postoperative bleeding leading the pack (n=12, 48%). No case of urethrocutaneous fistula was seen. We detected 17 cases (0.7%) of distal hypospadias in whom circumcisions were postponed till the time of hypospadias repairs. CONCLUSION: The main indication for infant circumcision in our environment was religious. The PC has good safety profile with few easily correctable early complications. Detailed attention to placement of ligature, selection of appropriate Plastibell size and adequate parental education are key to preventing post-procedure mishaps. PMID- 27200142 TI - [Bilateral rupture of the anterior cruciate ligament in a ski player treated with DIDT by arthroscopic surgery in one time]. AB - We report the case of a 25-year-old patient who suffered a ski accident that causing a serious knees sprain. The patient underwent immobilization by plaster knees. After 12 rehabilitation sessions, good progress was noticed in terms of pain. However, the patient is unstable when walking and a positive Trillat Lachman sign at both knees is observed. MRI of Knees confirmed a bilateral rupture of the anterior cruciate ligament (figures A, B). We conducted a ligament ACL with the DIDT technique on both knees, beginning with the left- side. After the surgery, everything was normal. X-ray controls (face and profile views) of both knees showed a good positioning of implants (figures C, D). Rehabilitation was undertaken the day following the surgery. Six months later, the patient was able to return to sport. PMID- 27200143 TI - [Vascular malformations in the Williams-Beuren syndrome: report of three new cases]. AB - The Williams-Beuren syndrome is a rare genetic disease. It combines classically specific facial dysmorphism, cardiovascular malformations and specific neuropsychological profile. We report three cases of Williams-Beuren syndrome in children with particular emphasis on vascular abnormalities observed on CT angiography and MR angiography. PMID- 27200144 TI - Near-infrared spectrometry in pregnancy: progress and perspectives, a review of literature. AB - Near-infrared spectroscopy (NIRS) allows continuous noninvasive monitoring of in vivo oxygenation in selected tissues. It has been used primarily as a research tool for several years, but it is seeing wider application in the clinical arena all over the world. It was recently used to monitor brain circulation in cardiac surgery, carotid endarteriectomy, neurosurgery and robotic surgery. According to the few studies used NIRS in pregnancy, it may be helpful to assess the impact of severe forms of preeclampsia on brain circulation, to evaluate the efficacy of different treatments. It may also be used during cesarean section to detect earlier sudden complications. The evaluation of placental function via abdominal maternal approach to detect fetal growth restriction is a new field of application of NIRS. PMID- 27200145 TI - [Pneumomediastinum during a dermatomyositis: a rare entity]. AB - Dermatomyositis is a connective characterized by inflammation of skeletal muscle with cutaneous manifestations. Their etiologies, still unknown, associate environmental and genetic factors. Among lung complications described, interstitial pneumopathies are common complications. Other complications are rarely reported as pneumomediastinum. We report a case of pneumomediastinum with aeric in massive skin dissection occurred in a patient with dermatomyositis. We will discuss the frequency, causes and pathophysiology of the disease according to the literature. PMID- 27200146 TI - Role of TFEB Mediated Autophagy, Oxidative Stress, Inflammation, and Cell Death in Endotoxin Induced Myocardial Toxicity of Young and Aged Mice. AB - Elderly patients are susceptible to sepsis. LPS induced myocardial injury is a widely used animal model to assess sepsis induced cardiac dysfunction. The age dependent mechanisms behind sepsis susceptibility were not studied. We analyzed age associated changes to cardiac function, cell death, inflammation, oxidative stress, and autophagy in LPS induced myocardial injury. Both young and aged C57BL/6 mice were used for LPS administration. The results demonstrated that LPS induced more cardiac injury (creatine kinase, lactate dehydrogenase, troponin I, and cardiac myosin-light chains 1), cardiac dysfunction (left ventricular inner dimension, LVID, and ejection fraction (EF)), cell death, inflammation, and oxidative stress in aged mice compared to young mice. However, a significant age dependent decline in autophagy was observed. Translocation of Transcription Factor EB (TFEB) to nucleus and formation of LC3-II were significantly reduced in LPS administered aged mice compared to young ones. In addition to that, downstream effector of TFEB, LAMP-1, was induced in response to LPS challenge in young mice. The present study newly demonstrates that TFEB mediated autophagy is crucial for protection against LPS induced myocardial injury particularly in aging senescent heart. Targeting this autophagy-oxidative stress-inflammation cell death axis may provide a novel therapeutic strategy for cardioprotection in the elderly. PMID- 27200147 TI - Age-Associated Changes in the Vascular Renin-Angiotensin System in Mice. AB - Background. This study evaluated whether the change in the renin-angiotensin system (RAS) is associated with arterial aging in mice. Methods. Histologic changes and expressions of transforming growth factor-beta (TGF-beta), collagen IV, fibronectin, angiotensin II (Ang II), angiotensin-converting enzyme (ACE), angiotensin-converting enzyme 2 (ACE2), angiotensin II type 1 receptor (AT1R), angiotensin II type 2 receptor (AT2R), prorenin receptor (PRR), Mas receptor (MasR), endothelial nitric oxide synthase (eNOS), NADPH oxidase 2 and oxidase 4 (Nox2 and Nox4), 8-hydroxy-2'-deoxyguanosine (8-OHdG), 3-nitrotyrosine, and superoxide dismutase 1 and dismutase 2 (SOD1 and SOD2) were measured in the thoracic aortas from 2-month-old, 12-month-old, and 24-month-old C57/BL6 mice. Results. Twenty-four-month-old mice showed significantly increased aortic media thickness and expressions of TGF-beta, collagen IV, and fibronectin, compared to 2-month-old and 12-month-old mice. The expressions of PRR, ACE, and Ang II, and AT1R-positive area significantly increased, whereas expressions of ACE2 and MasR and AT2R-positive area decreased with age. The expressions of phosphorylated serine(1177)-eNOS, SOD1, and SOD2 decreased, and the 8-OHdG-positive area and the 3-nitrotyrosine-positive area increased with age. The expression of Nox2 significantly increased with age, but that of Nox4 did not change. Conclusions. The enhanced PRR-ACE-Ang II-AT1R axis and reduced ACE2-MasR axis were associated with arterial aging in mice. PMID- 27200150 TI - Bilateral Thalamic and Right Fronto-temporo-parietal Gliomas in a 4 Years Old Child Diagnosed by Magnetic Resonance Imaging. AB - We report the neuroimaging findings of a 4-year-old girl with biopsy-proven bilateral thalamic and right fronto-temporo-parietal cortical gliomas, which are uncommon tumours involving the central nervous system. Despite their benignity, the prognosis is usually poor because of involvement of the thalamic nuclei and difficulty in surgical excision. These lesions have limited differential diagnoses that include metabolic, toxic, infective, vascular and neoplastic. Imaging characteristics on conventional Magnetic Resonance (MR), Magnetic Resonance Spectroscopy (MRS) and Diffusion tensor imaging (DTI) can further narrow the differential diagnosis and also provide additional information regarding the degree of involvement of adjacent brain tissue and white matter tracts around the lesions. PMID- 27200149 TI - Hepatitis C Virus NS5A Protein Triggers Oxidative Stress by Inducing NADPH Oxidases 1 and 4 and Cytochrome P450 2E1. AB - Replication of hepatitis C virus (HCV) is associated with the induction of oxidative stress, which is thought to play a major role in various liver pathologies associated with chronic hepatitis C. NS5A protein of the virus is one of the two key viral proteins that are known to trigger production of reactive oxygen species (ROS). To date it has been considered that NS5A induces oxidative stress by altering calcium homeostasis. Herein we show that NS5A-induced oxidative stress was only moderately inhibited by the intracellular calcium chelator BAPTA-AM and not at all inhibited by the drug that blocks the Ca(2+) flux from ER to mitochondria. Furthermore, ROS production was not accompanied by induction of ER oxidoreductins (Ero1), H2O2-producing enzymes that are implicated in the regulation of calcium fluxes. Instead, we found that NS5A contributes to ROS production by activating expression of NADPH oxidases 1 and 4 as well as cytochrome P450 2E1. These effects were mediated by domain I of NS5A protein. NOX1 and NOX4 induction was mediated by enhanced production of transforming growth factor beta1 (TGFbeta1). Thus, our data show that NS5A protein induces oxidative stress by several multistep mechanisms. PMID- 27200151 TI - Pulmonary Alveolar Microlithiasis - Clinico-Radiological dissociation - A case report with Radiological review. AB - Pulmonary alveolar microlithiasis (PAM) is a rare chronic lung disease characterized by deposition of intra alveolar calcium and phosphate in bilateral lung parenchyma with predominance in lower and mid zones. Etiology and pathogenesis is not fully understood. However, mutation in SLC34A2 gene that encodes a sodium phosphate co-transporter in alveolar type-II cells resulting in formation and accumulation of microliths rich in calcium phosphate due to impaired clearance is considered the cause of disease. Patients with PAM are asymptomatic till development of hypoxemia and cor pulmonale. It remains static, while in some it progresses to pulmonary fibrosis, respiratory failure and cor pulmonale. We report a case of 44 year old male patient presenting with progressive shortness of breath on exertion for one year in duration with dry cough, more since last six months. Chest radiograph showed dense micronodular opacities giving classical sandstorm appearance. High resolution computed tomography (HRCT) showed microcalcification, subpleural cystic changes and calcified pleura. Lung biopsy showed calcospherites within alveolar spaces. PMID- 27200153 TI - Extensive Erosion of Vertebral Bodies Due to a Chronic Contained Ruptured Abdominal Aortic Aneurysm. AB - This report describes a case of chronically ruptured abdominal aortic aneurysm contained within the lumbar vertebral bodies that presented with dull abdominal pain. Sudden, massive hemorrhage is an uncommon, yet well-known complication of an untreated abdominal aortic aneurysm. In addition, misleading clinical and radiological findings present difficult diagnostic challenges in such cases. This report emphasizes the findings obtained with multidetector computed tomography and delineates the differentiation of this condition from similar pathologies. PMID- 27200152 TI - Prostate Brachytherapy seed migration to the Bladder presenting with Gross Hematuria. AB - We present the radiologic findings in a case of prostate brachytherapy seed migration to the bladder presenting as gross hematuria. While prostate brachytherapy seed implantation is considered a relatively safe procedure, migration is not uncommon; however, it is usually clinically silent and the seeds most commonly migrate to the lungs through the venous circulation via the periprostatic venous plexus. Our case illustrates that local erosion is possible, can be symptomatic, and therefore must be considered when evaluating select patients. PMID- 27200148 TI - The Role of Mitochondrial Reactive Oxygen Species in Cardiovascular Injury and Protective Strategies. AB - Ischaemia/reperfusion (I/R) injury of the heart represents a major health burden mainly associated with acute coronary syndromes. While timely coronary reperfusion has become the established routine therapy in patients with ST elevation myocardial infarction, the restoration of blood flow into the previously ischaemic area is always accompanied by myocardial injury. The central mechanism involved in this phenomenon is represented by the excessive generation of reactive oxygen species (ROS). Besides their harmful role when highly generated during early reperfusion, minimal ROS formation during ischaemia and/or at reperfusion is critical for the redox signaling of cardioprotection. In the past decades, mitochondria have emerged as the major source of ROS as well as a critical target for cardioprotective strategies at reperfusion. Mitochondria dysfunction associated with I/R myocardial injury is further described and ultimately analyzed with respect to its role as source of both deleterious and beneficial ROS. Furthermore, the contribution of ROS in the highly investigated field of conditioning strategies is analyzed. In the end, the vascular sources of mitochondria-derived ROS are briefly reviewed. PMID- 27200155 TI - Honoring our helpers. AB - This special issue of the Journal of Radiology Case Reports honors the reviewers who donated their time and expertise throughout the year 2015 to the high quality and success of this journal. PMID- 27200154 TI - Goldenhar syndrome with contralateral pulmonary aplasia: a rare association. AB - We present a case of a 13-year-old boy with clinical features of Goldenhar syndrome (hemifacial microsomia with malformed ears) and associated contralateral pulmonary aplasia. The patient did not have any associated respiratory symptoms. Pulmonary aplasia is an uncommon association of Goldenhar Syndrome. A case of contralateral pulmonary aplasia has been rarely reported in the literature to the best of our knowledge. PMID- 27200156 TI - Primary osteogenic osteosarcoma of the ethmoid sinus in an adolescent: case report. AB - Osteosarcomas of the craniofacial bones account for fewer than 10% of all osteosarcomas. Primary osteosarcomas of the nasal cavity and paranasal sinus are rare (0.5-8.1% of the osteosarcomas occur in this location). Because of the rarity of this presentation, we report a case of osteogenic osteosarcoma arising de novo from the ethmoid bone in a 13 year old male who presented with discharge from the right eye and headaches. We describe the imaging features of this rare tumor and provide a brief review of the literature. PMID- 27200157 TI - Apparent diffusion coefficient map of a case of extramedullary plasmacytoma. AB - Plasmacytomas are rare tumors, which arise from the monoclonal proliferation of malignant plasma cells. They may affect either the bony skeleton or rarely the soft tissues, the latter being referred to as extramedullary or extraosseous. We report a case of an extramedullary plasmacytoma that presented as a soft tissue mass involving the muscles of the left leg, in a patient who was previously treated for multiple myeloma. We describe the MR Imaging characteristics of the tumor and highlight the usefulness of diffusion-weighted imaging with apparent diffusion coefficient mapping. PMID- 27200158 TI - Percutaneous Approach for Removal of a Migrated Cystogastric Stent from a Pancreatic Pseudocyst: A Case Report and Review of the Literature. AB - Stent migration into pancreatic pseudocysts during endosonographic (EUS) cystogastrostomy is a relatively rare complication. The migrated stent may induce, if it remains within the body, infection and perforation. Therefore, retrieval and/or re-stenting is necessary. Endoscopic retrieval is commonly attempted first. However, it is technically challenging and largely dependent on the skill of the endoscopists; if retrieval is unsuccessful, surgery is usually carried out. We report a case of stent migration into a pancreatic pseudocyst that was retrieved with a percutaneous approach under imaging guidance using a simple technique with available devices. A technique that enhances the role of interventional radiology in the management of this rare complication. PMID- 27200159 TI - Late Migration of a Covered Stent into the Stomach after Repair of a Splenic Artery Pseudoaneurysm. AB - We would like to report our experience of a rather rare complication that occurred in a 76-year old patient tree years after endovascular repair of a splenic artery pseudoaneurysm with a covered stent. Three years after stent insertion, the patient complained of mild abdominal pain and melena; it was revealed endoscopically that the covered stent has eroded the stomach wall and migrated into the stomach. The splenic artery is the most common location among the spectrum of potential presentation sites of visceral arteries aneurysms and pseudoaneurysms. Endovascular treatment with the use of coils or stents is the first option due to lower morbidity and mortality than open surgery. Endovascular repair may also lead to complications and patients need to be followed up in order to confirm aneurysm sealing, and exclude late complication. Minor stent graft migration may occur in the long term, however extra vascular migration is extremely rare. PMID- 27200161 TI - Capecitabine-induced leukoencephalopathy involving the bilateral corticospinal tracts. AB - An 80 year old lady with a history of metastatic sigmoid carcinoma presented with expressive dysphasia and unsteady gait 4 days after commencement of adjuvant capecitabine chemotherapy. MRI demonstrated restricted diffusion and T2/FLAIR hyperintensity involving the course of the bilateral corticospinal tracts, the corpus callosum and the middle cerebellar peduncles. Discontinuation of chemotherapy lead to symptom resolution in 2 days; repeat MRI at 2 months demonstrated reversal of the diffusion changes and improvement of the previous T2W/FLAIR hyperintensity. This report describes the first case of capecitabine induced leukoencephalopathy causing restricted diffusion along the corticospinal tracts, which should be differentiated from other entities that involve the corticospinal tracts (i.e. amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS), hypoglycemic coma, etc.). PMID- 27200160 TI - Congenital anterior urethrocutaneous fistula at the penoscrotal junction with proximal penile megalourethra: A case report. AB - Congenital anterior urethrocutaneous fistula and megalourethra are both rare anomalies. These anomalies are commonly associated with other anorectal or genitourinary anomalies and evaluated with voiding cystourethrography. We examined a 34-month-old boy who presented with a fistula at the penoscrotal junction. A voiding cystourethrogram showed a jet of urine coming through the fistula and proximal saccular dilatation of the penile urethra. We present the imaging findings of the first case of an association between a congenital anterior urethrocutaneous fistula at the penoscrotal junction and a proximal penile megalourethra. We also discuss the etiology, management, and differential diagnosis of this entity, and review the literature. PMID- 27200162 TI - Male Pectoral Implants: Radiographic Appearance of Complications. AB - There has been a significant surge in aesthetic chest surgery for men in the last several years. Male chest enhancement is performed with surgical placement of a solid silicone pectoral implant. In the past, male chest correction and implantation were limited to the treatment of men who had congenital absence or atrophy of the pectoralis muscle and pectus excavatum deformity. But today, the popularization of increased chest and pectoral size fostered by body builders has more men desiring chest correction with implantation for non-medical reasons. We present a case of a 44-year-old, male with a displaced left pectoral implant with near extrusion and with an associated peri-implant soft tissue mass and fluid collection. While the imaging of these patients is uncommon, our case study presents the radiographic findings of male chest enhancement with associated complications. PMID- 27200163 TI - Incidental Anterior Cruciate Ligament Calcification: Case Report. AB - The calcification of knee ligaments is a finding noted only in a handful of case reports. The finding of an anterior cruciate ligament calcification has been reported once in the literature. Comparable studies involving the posterior cruciate ligament, medial collateral ligament and an ossicle within the anterior cruciate ligament are likewise discussed in reports of symptomatic patients. We report a case of incidentally discovered anterior cruciate ligament calcification. We discuss the likely etiology and clinical implications of this finding. PMID- 27200165 TI - A Rare Triad of Giant Occipital Encephalocele with Lipomyelomeningocele, Tetralogy of Fallot, and Situs Inversus. AB - Giant encephalocele is an uncommon congenital anomaly with very few published reports available in the English literature. Tetralogy of Fallot associated with situs inversus is also infrequently reported. To our knowledge there are no published reports of an association between giant encephalocele and Tetralogy of Fallot. The additional finding of situs inversus results in a rare pathologic triad, not heretofore described. PMID- 27200164 TI - Treatment of Hypersplenism by Partial Splenic Embolization Through Gastric Collaterals. AB - We report a case of Chronic lymphocytic leukemia (CLL) with associated hypersplenism, that was referred to us for partial splenic embolization (PSE) as the patient was not a surgical candidate for splenectomy. Initially, we were not successful in catheterizing the splenic artery from the celiac trunk due to significant atherosclerotic disease. Therefore, we successfully managed to access the distal splenic artery through patent gastro-epiploic collateral circulation along the greater curvature of the stomach. Partial splenic embolization was successfully performed and resulted in improvement of the patient's peripheral blood cell count as well as 60-70% reduction in the size of the spleen on follow up. Our case highlights an alternative pathway for splenic artery embolization when catheterization of the splenic artery is not feasible. To our knowledge, the use of gastro-epiploic collaterals to embolize the spleen has not been previously reported in literature. PMID- 27200166 TI - Radiological features of a rare case of pancreatic panniculitis presenting in bilateral lower extremities. AB - Pancreatic panniculitis is a rare cutaneous presentation in patients with pancreatic pathology. While it presents as cutaneous inflammation with painful and erythematous nodules which demonstrate ulceration, imaging features of this pathology are seldom described. The common sites of involvement are the extremities. It demonstrates characteristic histological features of lobular panniculitis with ghost cells. MR imaging with its excellent soft tissue contrast can be helpful in confirming the diagnosis, demonstrating imaging features of fat necrosis with surrounding inflammation as demonstrated in our patient. PMID- 27200167 TI - Angioleiomyoma of the falx. AB - A 43-year-old man arrived at the emergency department following a syncopal episode. Computed tomography and magnetic resonance images demonstrated a small interhemispheric, anterior parafalcine mass that mimicked a meningioma. Surgical excision and subsequent pathologic evaluation revealed an angioleiomyoma and the patient recovered without incident. Angioleiomyomas are classified as benign smooth muscle tumors and are classically seen in adult females arising in the soft tissues of the lower extremities. Although rare, these masses have been described in various intracranial locations, usually extra-axially. A comprehensive review of the literature and discussion are provided, emphasizing histopathologic and imaging features of this uncommon intracranial neoplasm. PMID- 27200168 TI - Gastric infarction following gastric bypass surgery. AB - Gastric infarction is an extremely rare occurrence owing to the stomach's extensive vascular supply. We report an unusual case of gastric infarction following gastric bypass surgery. We describe the imaging findings and discuss possible causes of this condition. PMID- 27200169 TI - Rare Case of Retroperitoneal Lipomatosis in an Indian Woman. AB - Retroperitoneal lipomatosis is a rare but distinct clinicopathological entity characterized by non encapsulated lipoma development in the retroperitoneum. Presenting complaints in the early stages are vague, and patients with retroperitoneal lipomatosis are often misdiagnosed because considerable abnormality is not detected by abdomino-pelvic sonography. However, because of the progressive nature of this lesion, most patients eventually present with varying degrees of urinary outflow obstruction and end stage renal disease, or bladder malignancies in few cases. Here we report a case of a 35-year-old Indian woman presenting with complaints of diffuse lumps in the abdomen and constipation. Based on the findings of the imaging [sonography and computed tomography (CT) scan] studies, benign retroperitoneal lipomatosis was preopreratively diagnosed and a confirmatory exploratory laprotomy was performed. Furthermore, we discuss the imaging findings obtained using various radiological modalities such as plain radiographs, intravenous urography, barium enema, sonography, CT and magnetic resonance imaging (MRI). We also discuss the etiopathogenesis, demographics, and various differential diagnoses of retroperitoneal lipomatosis. PMID- 27200170 TI - Isolated Teres Major Rupture: A case report with a suggested dedicated imaging protocol and review of the literature. AB - Isolated injuries to the teres major muscle occur in competitive sporting activities such as baseball pitching, hockey and tennis. We report a similar event of a physically fit man sustaining an isolated teres major rupture while waterskiing. Non-operative management was chosen, with pain resolution and no appreciable functional limitations at follow up. Because teres major muscle injury was suspected at the time of imaging, we present a dedicated imaging protocol to optimize assessment for teres major injury. PMID- 27200171 TI - A rare case of atypical skull base meningioma with perineural spread. AB - Atypical meningioma is a rare cause of perineural tumour spread. In this report, we present the case of a 46-year-old female with an atypical meningioma of the skull base demonstrating perineural tumour spread. We describe the imaging features of this condition and its distinguishing features from other tumours exhibiting perineural spread. PMID- 27200172 TI - Incidentally Discovered Middle Mesenteric Artery In A Renal Donor. AB - The middle mesenteric artery is a very rare anomalous artery originating from the ventral surface of the abdominal aorta in-between the superior mesenteric artery and inferior mesenteric artery. We identified a middle mesenteric artery during abdominal computed tomographic angiography in a renal donor patient as a part of his work up. The middle mesenteric artery branched out into ileal and ileocolic arteries, supplying the terminal ileal loops as well as the cecum. The anomalous artery had no effect on patient's eligibility as a renal donor candidate. PMID- 27200173 TI - A Torted Ruptured Intra-abdominal Testicular Seminoma Presenting As An Acute Abdomen. AB - The susceptibility of the undescended testis to malignant transformation is well documented. The most common location of the undescended testis is within the inguinal canal, with only a minority located within the abdominal cavity. When a testicular mass develops, the risk of torsion increases. We describe a large intra-abdominal testicular seminoma that had undergone torsion, rupture and haemorrhage, presenting as an acute abdomen. A 30 year old man presented to the emergency department with right iliac fossa pain. Computed tomography in the emergency department showed haemoperitoneum and a torted large left testicular mass, likely malignant. The patient underwent laparotomy and excision of the mass. Histologic examination revealed a grossly enlarged seminomatous testis which had torted and ruptured. While pre-operative imaging diagnosis of an intra abdominal testicular seminoma has been published, reports are few. To the best of the author's knowledge pre-operative imaging diagnosis of a malignant testicular mass with torsion and intra-abdominal haemorrhage presenting as an acute abdomen has not been described before. PMID- 27200174 TI - Isolated Fallopian Tube Torsion With Fimbrial Cyst In A 10 Year-old Girl Diagnosed By Ultrasound: A Case Report. AB - Torsion of the fallopian tube without the involvement of the ipsilateral ovary is a rare but important cause of acute abdominal pain in women as it is a surgical emergency. Although uncommon, it should be considered as one of the differential diagnosis in female children presenting with acute lower abdominal or pelvic pain. The diagnosis of isolated fallopian tube torsion is difficult pre operatively and is often made during laparoscopic or surgical exploration because diagnostic features are usually non-specific. In this report, we present a case of isolated fallopian tube torsion with fimbrial cyst in a young female patient diagnosed pre-operatively by ultrasound. PMID- 27200176 TI - Allosteric Glutaminase Inhibitors Based on a 1,4-Di(5-amino-1,3,4-thiadiazol-2 yl)butane Scaffold. AB - A series of allosteric kidney-type glutaminase (GLS) inhibitors were designed and synthesized using 1,4-di(5-amino-1,3,4-thiadiazol-2-yl)butane as a core scaffold. A variety of modified phenylacetyl groups were incorporated into the 5-amino group of the two thiadiazole rings in an attempt to facilitate additional binding interactions with the allosteric binding site of GLS. Among the newly synthesized compounds, 4-hydroxy-N-[5-[4-[5-[(2-phenylacetyl)amino]-1,3,4-thiadiazol-2 yl]butyl]-1,3,4-thiadiazol-2-yl]-benzeneacetamide, 2m, potently inhibited GLS with an IC50 value of 70 nM, although it did not exhibit time-dependency as seen with CB-839. Antiproliferative effects of 2m on human breast cancer lines will be also presented in comparison with those observed with CB-839. PMID- 27200175 TI - Inferior vena cava filter penetration following Whipple surgical procedure causing ureteral injury. AB - We report a case of an indwelling inferior vena cava filter that penetrated the IVC wall after Whipple's pancreatico-duodenectomy procedure performed in a patient with ampullary carcinoma, resulting in right ureteral injury and obstruction with subsequent hydroureter and hydronephrosis. This was incidentally discovered on a computed tomography scan performed as routine follow up to evaluate the results of the surgery. We retrieved the inferior vena cava filter and placed a nephrostomy catheter to relieve the ureteral obstruction. Our case highlights the importance of careful inferior vena cava manipulation during abdominal surgery in the presence of an inferior vena cava filter, and the option of temporary removal of the filter to be placed again after surgery in order to avoid this complication, unless protection is required against clot migration during the surgical procedure. PMID- 27200177 TI - Genome sequence and description of Actinomyces polynesiensis str. MS2 sp. nov. isolated from the human gut. AB - Actinomyces polynesiensis strain MS2 gen. nov., sp. nov. is a newly proposed genus within the family Actinomycetaceae, isolated from the stools of a healthy individual in Raiatea Island (French Polynesia, South Pacific). Actinomyces massiliensis is an anaerobic, Gram-positive organism. Here we describe the features of this organism, together with the complete genome sequence and annotation-2 943 271 bp with a 70.80% G+C content, assembled into 15 scaffolds and containing 2080 genes. PMID- 27200178 TI - Romboutsia timonensis, a new species isolated from human gut. AB - The exploration of the human microbiome was recently revolutionized by microbial culturomics and taxonogenomics. Thanks to this approach, we report here the main characteristics of Romboutsia timonensis strain Marseille-P326, a new bacterium isolated from the right human colon by colonoscopy in a 63-year-old French man with severe anaemia with melaena. PMID- 27200179 TI - Obesity and the receipt of influenza and pneumococcal vaccination: a systematic review and meta-analysis. AB - BACKGROUND: Obesity is a risk factor for inadequate receipt of recommended preventive care services. The objective of this study was to assess the relationship between increasing body mass index and receipt of influenza and pneumococcal vaccinations. A systematic review of the PubMed, Embase, and Web of Science databases was conducted from January 1966 to May 2015 for cohort and cross-sectional studies that assessed the relationship between body mass index and the receipt of vaccinations for influenza and pneumococcus. Separate meta analyses by obesity classification were performed using a random effects model. RESULTS: Six cross-sectional and three cohort studies were included. Average vaccine uptake was 50.4 % for influenza vaccination and 34.6 % for pneumococcal vaccination. Compared to normal weight patients, combined odds ratio (95 % confidence interval) for influenza vaccination was 1.11 (95 % CI 0.97-1.25) for obese (>=30 kg/m(2)) patients. When the outcome was reported by obesity class, combined odds ratios of influenza vaccination were 1.13 (95 % CI 1.02-1.24) for Class I (30-34.9 kg/m(2)) obesity, 1.21 (95 % CI 1.05-1.37) for Class II obesity (35-39.9 kg/m(2)), and 1.19 (95 % CI 0.95-1.42) for Class III obesity (>=40 kg/m(2)) patients. Compared to normal weight patients, combined odds ratio of pneumococcal vaccination were 1.20 (95 % CI 1.13-1.27) for obese patients. When the outcome was reported by obesity class, combined odds ratios were 1.08 (95 % CI 1.04-1.13) for Class I obesity patients, 1.13 (95 % CI 1.10-1.16) for Class II obesity patients, and 1.26 (95 % CI 1.15-1.38) for Class III obesity patients for pneumococcal vaccination. CONCLUSIONS: Combined findings from the current literature suggest that adults with obesity are more likely than non-obese peers to receive vaccination for influenza and pneumococcus. However, suboptimal vaccination coverage was observed across all body sizes, so future interventions should focus on improving vaccination rates for all adults. PMID- 27200180 TI - Dry aging of beef; Review. AB - The present review has mainly focused on the specific parameters including aging (aging days, temperature, relative humidity, and air flow), eating quality (flavor, tenderness and juiciness), microbiological quality and economic (shrinkage, retail yields and cost) involved beef dry aging process. Dry aging is the process where beef carcasses or primal cuts are hanged and aged for 28 to 55 d under controlling environment conditions in a refrigerated room with 0 degrees to 4 degrees C and with relative humidity of 75 to 80 %. However there are various opinions on dry aging procedures and purveyors of such products are passionate about their programs. Recently, there has been an increased interest in dry aging process by a wider array of purveyors and retailers in the many countries. Dry aging process is very costly because of high aging shrinkage (6 to15 %), trims loss (3 to 24 %), risk of contamination and the requirement of highest grades meat with. The packaging in highly moisture-permeable bag may positively impact on safety, quality and shelf stability of dry aged beef. The key effect of dry aging is the concentration of the flavor that can only be described as "dry-aged beef". But the contribution of flavor compounds of proteolysis and lipolysis to the cooked dry aged beef flavor is not fully known. Also there are limited scientific studies of aging parameters on the quality and palatability of dry aged beef. PMID- 27200181 TI - The bright side of reactive oxygen species: lifespan extension without cellular demise. AB - Oxidative stress and the generation of reactive oxygen species (ROS) can lead to mitochondrial dysfunction, DNA damage, protein misfolding, programmed cell death with apoptosis and autophagy, and the promotion of aging -dependent processes. Mitochondria control the processing of redox energy that yields adenosine triphosphate (ATP) through the oxidation of glucose, pyruvate, and nicotinamide adenine dinucleotide. Ultimately, the generation of ROS occurs with the aerobic production of ATP. Although reduced levels of ROS may lead to tolerance against metabolic, mechanical, and oxidative stressors and the generation of brief periods of ROS during ischemia-reperfusion models may limit cellular injury, under most circumstances ROS and mitochondrial dysfunction can lead to apoptotic caspase activation and autophagy induction that can result in cellular demise. Yet, new work suggests that ROS generation may have a positive impact through respiratory complex I reverse electron transport that can extend lifespan. Such mechanisms may bring new insight into clinically relevant disorders that are linked to cellular senescence and aging of the body's system. Further investigation of the potential "bright side" of ROS and mitochondrial respiration is necessary to target specific pathways, such as the mechanistic target of rapamycin, nicotinamidases, sirtuins, mRNA decoupling and protein expression, and Wnt signaling, that can impact oxidative stress-ROS mechanisms to extend lifespan and eliminate disease onset. PMID- 27200182 TI - Properties of Retinal Precursor Cells Grown on Vertically Aligned Multiwalled Carbon Nanotubes Generated for the Modification of Retinal Implant-Embedded Microelectrode Arrays. AB - Background. To analyze the biocompatibility of vertically aligned multiwalled carbon nanotubes (MWCNT), used as nanomodification to optimize the properties of prostheses-embedded microelectrodes that induce electrical stimulation of surviving retinal cells. Methods. MWCNT were synthesized on silicon wafers. Their growth was achieved by iron particles (Fe) or mixtures of iron-platinum (Fe-Pt) and iron-titanium (Fe-Ti) acting as catalysts. Viability, growth, adhesion, and gene expression of L-929 and retinal precursor (R28) cells were analyzed after nondirect and direct contact. Results. Nondirect contact had almost no influence on cell growth, as measured in comparison to reference materials with defined levels of cytotoxicity. Both cell types exhibited good proliferation properties on each MWCNT-coated wafer. Viability ranged from 95.9 to 99.8%, in which better survival was observed for nonfunctionalized MWCNT generated with the Fe-Pt and Fe Ti catalyst mixtures. R28 cells grown on the MWCNT-coated wafers showed a decreased gene expression associated with neural and glial properties. Expression of the cell cycle-related genes CCNC, MYC, and TP53 was slightly downregulated. Cultivation on plasma-treated MWCNT did not lead to additional changes. Conclusions. All tested MWCNT-covered slices showed good biocompatibility profiles, confirming that this nanotechnology is a promising tool to improve prostheses bearing electrodes which connect with retinal tissue. PMID- 27200183 TI - Different Strategies for the Treatment of Age-Related Macular Degeneration in China: An Economic Evaluation. AB - Purpose. To assess the cost-effectiveness of bevacizumab compared to ranibizumab, verteporfin photodynamic therapy (PDT), and usual care for the treatment of age related macular degeneration (AMD) in China. Methods. A Markov model was developed according to patient visual acuity (VA) in the better-seeing eye (Snellen scale). Four cohorts of patients were treated with one of the following therapies: bevacizumab, ranibizumab, PDT, or usual care. Clinical data related to treatments were obtained from published randomized clinical trials. Direct medical costs and resource utilization in the Chinese health care setting were taken into account. Health and economic outcomes were evaluated over a lifetime horizon. Sensitivity analyses were performed. Results. Treatment with ranibizumab provided the greatest gains in quality-adjusted life-years (QALYs). The cost per marginal QALY gained with bevacizumab over usual care was $1,258, $3,803, and $2,066 for the predominantly classic, minimally classic, and occult lesions, respectively. One-way sensitivity analysis showed considerably influential factors, such as utility values and effectiveness data. Probabilistic sensitivity analysis indicated that, compared to usual care, PDT and ranibizumab most cases would be cost-effective in the bevacizumab arm at a threshold of $7,480/QALY. Conclusion. Bevacizumab can be a cost-effective option for the treatment of AMD in the Chinese setting. PMID- 27200184 TI - Prevalence and Sociodemographic Determinants of Hypertension History among Women in Reproductive Age in Ghana. AB - Background. Hypertension is a global health problem. Yet, studies on hypertension rarely focus on women in Ghana. The purpose of this study is to ascertain the prevalence and sociodemographic determinants of hypertension history among Ghanaian women in reproductive age. Methods. This study used data from the 2014 Ghana Demographic and Health Survey. Bivariate and logistic regression analyses were carried out to ascertain the prevalence and determinants of hypertension history among the respondents. Results. The study found that the overall prevalence of hypertension history among the respondents was 7.5%; however, there were vast variations within most of the sociodemographic categories. Age, level of education, marital status, work status, and wealth status had a significant relationship with hypertension history among the respondents. Women in advanced age groups, highly educated, married, and widowed/divorced/separated, nonworking women, and women from wealthy households were at higher risk of having hypertension history. Conclusion. Myriads of sociodemographic factors determine the hypertension history of women in Ghana. It is therefore essential to target medical and psychosocial hypertension interventions at Ghanaian women in the higher risk groups. PMID- 27200187 TI - Additional Analgesia for Central Venous Catheter Insertion: A Placebo Controlled Randomized Trial of Dexmedetomidine and Fentanyl. AB - We aimed to show that a single preprocedural dose of either dexmedetomidine or fentanyl reduces procedural pain and discomfort and provides clinically acceptable sedation. In this prospective, double-blind study, sixty patients scheduled for elective surgery and requiring planned central venous catheter insertion were randomized to receive dexmedetomidine (1 MUg/kg), fentanyl (1 MUg/kg), or 0.9% normal saline intravenously over ten minutes followed by local anesthetic field infiltration before attempting central venous catheterization. The primary outcome measures are assessment and analysis of pain, discomfort, and sedation level before, during, and after the central venous catheter insertion at five time points. The median (IQR) pain score is worst for normal saline group at local anaesthetic injection [6 (4-6.7)] which was significantly attenuated by addition of fentanyl [3 (2-4)] and dexmedetomidine [4 (3-5)] in the immediate postprocedural period (P = 0.001). However, the procedure related discomfort was significantly lower in dexmedetomidine group compared to fentanyl group in the first 10 min of procedure after local anaesthetic Injection (P = 0.001). Fentanyl is more analgesically efficient for central venous catheter insertion along with local anaesthetic injection. However, dexmedetomidine has the potential to be superior to fentanyl and placebo in terms of providing comfort to the patients during the procedure. PMID- 27200185 TI - The Association of Physical Activity during Weekdays and Weekend with Body Composition in Young Adults. AB - Physical activity (PA) is a key contributor in long-term weight management but there remains limited research on the association between weekly PA patterns and weight change. The purpose of the present study was to examine the prospective association between weekly PA patterns and weight change in generally healthy young adults. Anthropometric measurements, including dual X-ray absorptiometry, were obtained every 3 months over a period of one year in 338 adults (53% male). At each measurement time, participants wore a multisensor device for a minimum of 10 days to determine total daily energy expenditure and time spent sleeping, sedentary, in light PA (LPA), in moderate PA (MPA), and in vigorous PA (VPA). PA did not differ between weekdays and the weekend at baseline. Twenty-four-hour sleep time, however, was significantly longer during weekends compared to weekdays, which was associated with less time spent sedentary. Weight loss was associated with a significant increase in LPA at the expense of sedentary time during the weekend but not during weekdays. Regression analyses further revealed an inverse association between change in VPA during the weekend and body composition at 12-month follow-up. Taken together, these results suggest that weekend PA plays an important role in long-term weight management. PMID- 27200186 TI - Enteral Glutamine Administration in Critically Ill Nonseptic Patients Does Not Trigger Arginine Synthesis. AB - Glutamine supplementation in specific groups of critically ill patients results in favourable clinical outcome. Enhancement of citrulline and arginine synthesis by glutamine could serve as a potential mechanism. However, while receiving optimal enteral nutrition, uptake and enteral metabolism of glutamine in critically ill patients remain unknown. Therefore we investigated the effect of a therapeutically relevant dose of L-glutamine on synthesis of L-citrulline and subsequent L-arginine in this group. Ten versus ten critically ill patients receiving full enteral nutrition, or isocaloric isonitrogenous enteral nutrition including 0.5 g/kg L-alanyl-L-glutamine, were studied using stable isotopes. A cross-over design using intravenous and enteral tracers enabled splanchnic extraction (SE) calculations. Endogenous rate of appearance and SE of glutamine citrulline and arginine was not different (SE controls versus alanyl-glutamine: glutamine 48 and 48%, citrulline 33 versus 45%, and arginine 45 versus 42%). Turnover from glutamine to citrulline and arginine was not higher in glutamine administered patients. In critically ill nonseptic patients receiving adequate nutrition and a relevant dose of glutamine there was no extra citrulline or arginine synthesis and glutamine SE was not increased. This suggests that for arginine synthesis enhancement there is no need for an additional dose of glutamine when this population is adequately fed. This trial is registered with NTR2285. PMID- 27200188 TI - Growth Hormone-Releasing Peptide 6 Enhances the Healing Process and Improves the Esthetic Outcome of the Wounds. AB - In addition to its cytoprotective effects, growth hormone-releasing peptide 6 (GHRP-6) proved to reduce liver fibrotic induration. CD36 as one of the GHRP-6 receptors appears abundantly represented in cutaneous wounds granulation tissue. The healing response in a scenario of CD36 agonistic stimulation had not been previously investigated. Excisional full-thickness wounds (6 mmO) were created in the dorsum of Wistar rats and topically treated twice a day for 5 days. The universal model of rabbit's ears hypertrophic scars was implemented and the animals were treated daily for 30 days. Treatments for both species were based on a CMC jelly composition containing GHRP-6 400 MUg/mL. Wounds response characterization included closure dynamic, RT-PCR transcriptional profile, histology, and histomorphometric procedures. The rats experiment indicated that GHRP-6 pharmacodynamics involves attenuation of immunoinflammatory mediators, their effector cells, and the reduction of the expression of fibrotic cytokines. Importantly, in the hypertrophic scars rabbit's model, GHRP-6 intervention dramatically reduced the onset of exuberant scars by activating PPARgamma and reducing the expression of fibrogenic cytokines. GHRP-6 showed no effect on the reversion of consolidated lesions. This evidence supports the notion that CD36 is an active and pharmacologically approachable receptor to attenuate wound inflammation and accelerate its closure so as to improve wound esthetic. PMID- 27200189 TI - BMI, HOMA-IR, and Fasting Blood Glucose Are Significant Predictors of Peripheral Nerve Dysfunction in Adult Overweight and Obese Nondiabetic Nepalese Individuals: A Study from Central Nepal. AB - Objective. Nondiabetic obese individuals have subclinical involvement of peripheral nerves. We report the factors predicting peripheral nerve function in overweight and obese nondiabetic Nepalese individuals. Methodology. In this cross sectional study, we included 50 adult overweight and obese nondiabetic volunteers without features of peripheral neuropathy and 50 healthy volunteers to determine the normative nerve conduction data. In cases of abnormal function, the study population was classified on the basis of the number of nerves involved, namely, "<2" or ">=2." Multivariable logistic regression analysis was carried out to predict outcomes. Results. Fasting blood glucose (FBG) was the significant predictor of motor nerve dysfunction (P = 0.039, 95% confidence interval (CI) = 1.003-1.127). Homeostatic model assessment of insulin resistance (HOMA-IR) was the significant predictor (P = 0.019, 96% CI = 1.420-49.322) of sensory nerve dysfunction. Body mass index (BMI) was the significant predictor (P = 0.034, 95% CI = 1.018-1.577) in case of >=2 mixed nerves' involvement. Conclusion. FBG, HOMA IR, and BMI were significant predictors of peripheral nerve dysfunction in overweight and obese Nepalese individuals. PMID- 27200190 TI - The Efficacy of Functional Electrical Stimulation of the Abdominal Muscles in the Treatment of Chronic Constipation in Patients with Multiple Sclerosis: A Pilot Study. AB - Chronic constipation in patients with multiple sclerosis (MS) is common and the current methods of treatment are ineffective in some patients. Anecdotal observations suggest that functional electrical stimulation (FES) of the abdominal muscles may be effective in the management of constipation in these patients. Patients and Methods. In this exploratory investigation we studied the effects of FES on the whole gut transit time (WGTT) and the colonic transit time (CTT). In addition, we evaluated the treatment effect on the patients' constipation-related quality of life and on the use of laxatives and the use of manual bowel evacuation. FES was given for 30 minutes twice a day for a period of six weeks. Four female patients were studied. Results. The WGTT and CTT and constipation-related quality of life improved in all patients. The patients' use of laxatives was reduced. No adverse effects of FES treatment were reported. Conclusion. The findings of this pilot study suggest that FES applied to the abdominal muscles may be an effective treatment modality for severe chronic constipation in patients with MS. PMID- 27200191 TI - Leveraging Comparative Genomics to Identify and Functionally Characterize Genes Associated with Sperm Phenotypes in Python bivittatus (Burmese Python). AB - Comparative genomics approaches provide a means of leveraging functional genomics information from a highly annotated model organism's genome (such as the mouse genome) in order to make physiological inferences about the role of genes and proteins in a less characterized organism's genome (such as the Burmese python). We employed a comparative genomics approach to produce the functional annotation of Python bivittatus genes encoding proteins associated with sperm phenotypes. We identify 129 gene-phenotype relationships in the python which are implicated in 10 specific sperm phenotypes. Results obtained through our systematic analysis identified subsets of python genes exhibiting associations with gene ontology annotation terms. Functional annotation data was represented in a semantic scatter plot. Together, these newly annotated Python bivittatus genome resources provide a high resolution framework from which the biology relating to reptile spermatogenesis, fertility, and reproduction can be further investigated. Applications of our research include (1) production of genetic diagnostics for assessing fertility in domestic and wild reptiles; (2) enhanced assisted reproduction technology for endangered and captive reptiles; and (3) novel molecular targets for biotechnology-based approaches aimed at reducing fertility and reproduction of invasive reptiles. Additional enhancements to reptile genomic resources will further enhance their value. PMID- 27200192 TI - Neural Correlates of Dual-Task Walking: Effects of Cognitive versus Motor Interference in Young Adults. AB - Walking while concurrently performing cognitive and/or motor interference tasks is the norm rather than the exception during everyday life and there is evidence from behavioral studies that it negatively affects human locomotion. However, there is hardly any information available regarding the underlying neural correlates of single- and dual-task walking. We had 12 young adults (23.8 +/- 2.8 years) walk while concurrently performing a cognitive interference (CI) or a motor interference (MI) task. Simultaneously, neural activation in frontal, central, and parietal brain areas was registered using a mobile EEG system. Results showed that the MI task but not the CI task affected walking performance in terms of significantly decreased gait velocity and stride length and significantly increased stride time and tempo-spatial variability. Average activity in alpha and beta frequencies was significantly modulated during both CI and MI walking conditions in frontal and central brain regions, indicating an increased cognitive load during dual-task walking. Our results suggest that impaired motor performance during dual-task walking is mirrored in neural activation patterns of the brain. This finding is in line with established cognitive theories arguing that dual-task situations overstrain cognitive capabilities resulting in motor performance decrements. PMID- 27200193 TI - Thoracic Paravertebral Block, Multimodal Analgesia, and Monitored Anesthesia Care for Breast Cancer Surgery in Primary Lateral Sclerosis. AB - Objective. Primary lateral sclerosis (PLS) is a rare idiopathic neurodegenerative disorder affecting upper motor neurons and characterized by spasticity, muscle weakness, and bulbar involvement. It can sometimes mimic early stage of more common and fatal amyotrophic lateral sclerosis (ALS). Surgical patients with a history of neurodegenerative disorders, including PLS, may be at increased risk for general anesthesia related ventilatory depression and postoperative respiratory complications, abnormal response to muscle relaxants, and sensitivity to opioids, sedatives, and local anesthetics. We present a case of a patient with PLS and recent diagnosis of breast cancer who underwent a simple mastectomy surgery uneventfully under an ultrasound guided thoracic paravertebral block, multimodal analgesia, and monitored anesthesia care. Patient reported minimal to no pain or discomfort in the postoperative period and received no opioids for pain management before being discharged home. In patients with PLS, thoracic paravertebral block and multimodal analgesia can provide reliable anesthesia and effective analgesia for breast surgery with avoidance of potential risks associated with general anesthesia, muscle paralysis, and opioid use. PMID- 27200194 TI - Unilateral Maxillary First Molar Extraction in Class II Subdivision: An Unconventional Treatment Alternative. AB - The asymmetrical intra-arch relationship in Class II subdivision malocclusion poses challenges in the treatment planning and mechanotherapy of such cases. This case report demonstrates a treatment technique engaging unilateral extraction of a maxillary first molar and Begg fixed appliances. The outcome stability and the enhancing effect on the eruption of the third molar in the extraction segment were confirmed by a 4-year follow-up examination. PMID- 27200195 TI - Gallbladder Tuberculosis Mimicking Gallbladder Carcinoma: A Case Report and Literature Review. AB - Gallbladder tuberculosis (GT) is extremely rare, and it is difficult to differentiate from other gallbladder diseases, such as gallbladder carcinoma and Xanthogranulomatous Cholecystitis. A correct preoperative diagnosis of GT is difficult. The final diagnosis is usually made postoperatively according to surgical biopsy. Here, we report a case of a patient who underwent surgery with the preoperative diagnosis of gallbladder carcinoma. We reviewed the literature and present the process of differential diagnosis between two or more conditions that share similar signs or symptoms. PMID- 27200196 TI - Brucella Septic Arthritis: Case Reports and Review of the Literature. AB - Brucellosis is one of the commonest zoonotic infections worldwide. The disease is endemic in Saudi Arabia, the Middle East, and the Mediterranean area. Osteoarticular involvement is a frequent manifestation of brucellosis. It tends to involve the sacroiliac joints more commonly; however, spondylitis and peripheral arthritis are increasingly reported. Brucellosis can be overlooked especially in the presence of companion bacteria. Hence, it should be suspected in all patients with septic arthritis in endemic areas or in patients visiting such areas. PMID- 27200198 TI - Febuxostat and Increased Dialysis as a Treatment for Severe Tophaceous Gout in a Hemodialysis Patient. AB - Uric acid accumulates in renal failure and is thought to be a uremic toxin-that is, higher levels of uric acid are more damaging to the kidneys. Urate crystals can precipitate in the kidney tubules, cause urate stones, and promote inflammatory changes in the renal interstitium and vascular endothelium. Uric acid is also a small non-protein-bound molecule and therefore easily dialyzable. Here, we present the case of an anuric hemodialysis patient with severe tophaceous gout who regained some renal function and whose gout burden significantly decreased resulting in marked improvement in functional status using a new gout medication, febuxostat, and increased frequency of dialysis. PMID- 27200197 TI - Multifocal Aeromonas Osteomyelitis in a Child with Leukemia. AB - Aeromonas hydrophila is a Gram negative organism causing both intestinal and extraintestinal disease. The case of a 14-year-old girl with underlying immunodeficiency and leukemia who developed systemic A. hydrophila infection is described in this report. While in deep bone marrow aplasia she developed fever, severe pain in the lower extremities, and swelling of the left femur. Blood culture showed Escherichia coli and A. hydrophila whereas pus culture from the soft tissue swelling showed the presence of A. hydrophila. Imaging studies showed diffuse osteolytic lesions. Patient received 5 months of intravenous and oral antibiotics and she improved clinically whereas the radiology findings persisted. PMID- 27200199 TI - An Unusual Cause of Subacute Headache in a Patient Undergoing Chemotherapy for Advanced Testicular Nonseminomatous Germ Cell Tumour. AB - Testicular (germ cell) cancer is a model of a chemocurable malignancy and tends to have a favourable prognosis even in advanced stages due to exquisite sensitivity to platinum-based chemotherapy. However, both acute and longer-term toxicities of multiagent chemotherapy remain significant as causes of morbidity, very occasionally mortality, and impaired quality-of-life. Here, we report a case of acute cerebral venous sinus thrombosis occurring within 10 days of chemotherapy initiation in a young patient without comorbidities, whose only predisposing factors were malignancy, chemotherapy, and perhaps mild dehydration. The clinical presentation was also unusual with headache of moderate severity only without focal or global neurologic deficits. We suspect that cisplatin may have had direct vasculotoxic effects. The patient recovered fully after short duration anticoagulation but oncologists must remain aware of unusual and unpredictable complications of cytotoxic treatment. PMID- 27200200 TI - A Rare Case of Bilateral Patellar Tendon Ruptures: A Case Report and Literature Review. AB - Bilateral patellar tendon ruptures are rare. The majority of case reports describing bilateral patellar tendon ruptures have occurred in patients with predisposing factors to tendinopathy. We describe a case of bilateral patellar tendon rupture sustained following minimal trauma by a patient with no systemic disease or history of steroid use. Due to the rarity of this injury, clinical suspicion is low. It is reported that 38% of patellar tendon ruptures are misdiagnosed initially. Therefore careful history taking and physical examination is integral in ensuring a diagnosis is achieved for early primary repair. We discuss the aetiology of spontaneous tendon rupture and report a literature review of bilateral patellar tendon ruptures. PMID- 27200201 TI - Horner's Syndrome Incidental to Medullary Thyroid Carcinoma Excision: Case Report and Brief Literature Review. AB - Horner's syndrome is characterized by a combination of ipsilateral miosis, blepharoptosis, enophthalmos, facial anhidrosis, and iris heterochromia in existence of congenital lesions. The syndrome results from a disruption of the ipsilateral sympathetic innervation of the eye and ocular adnexa at different levels. Though rare, thyroid and neck surgery could be considered as possible causes of this clinical entity. We present a case of Horner's syndrome in a patient after total thyroidectomy and neck dissection for medullary thyroid cancer with neck nodal disease and attempt a brief review of the relevant literature. PMID- 27200202 TI - Osseointegrated Implants: An Alternative Approach in Patients with Bilateral Auricular Defects due to Chemical Assault. AB - Acid attacks committed as crimes of passion are unfortunately becoming far from infrequent occurrence. The injuries sustained in such attacks mainly involve the face and trunk, with the acid causing cutaneous and subcutaneous tissue burns that can result in permanent scarring, loss of the nose or external ear, and severe visual impairment. Different surgical solutions have been proposed for reconstruction of the auricle following loss of the ear through traumatic injury or cancer or in patients with congenital defects: surgical reconstruction may involve the insertion of an autogenous rib cartilage framework or the use of a porous polymer material inserted into an expanded postauricular flap. Reconstruction with rib cartilage has given good results but requires more than one surgical step and may be associated with adverse events involving both the donor site and the recipient site, while rejections of polymeric prostheses have been reported following their insertion into expanded postauricular flaps. The use of a titanium dowel-retained silicone prosthesis, in which the dowel is anchored to the temporal bone, is a surgical possibility, indicated particularly in cases of pinna resection due to tumour or auricular scarring following traumatic injury. PMID- 27200203 TI - Acute Alithiasic Cholecystitis and Human Herpes Virus Type-6 Infection: First Case. AB - A three-year-old male child presented with erythematous maculopapular nonpruritic generalized rash, poor feeding, vomiting, and cramping generalized abdominal pain. He was previously healthy and there was no family history of immunologic or other diseases. On examination he was afebrile, hemodynamically stable, with painful palpation of the right upper quadrant and positive Murphy's sign. Laboratory tests revealed elevated inflammatory markers, elevated aminotransferase activity, and features of cholestasis. Abdominal ultrasound showed gallbladder wall thickening of 8 mm with a positive sonographic Murphy's sign, without gallstones or pericholecystic fluid. Acute Alithiasic Cholecystitis (AAC) was diagnosed. Tests for underlying infectious causes were negative except positive blood specimen for Human Herpes Virus Type-6 (HHV-6) by polymerase chain reaction. With supportive therapy the child became progressively less symptomatic with gradual improvement. The child was discharged on the sixth day, asymptomatic and with improved analytic values. Two months later he had IgM negative and IgG positive antibodies (1/160) for HHV-6, which confirmed the diagnosis of previous infection. In a six-month follow-up period he remains asymptomatic. To the best of our knowledge, this represents the first case of AAC associated with HHV-6 infection. PMID- 27200204 TI - Vascular Anomalies in Pancreaticoduodenectomy: A Lesson Learned. AB - It is essential to identify any variant anatomy prior to surgery as this could have a drastic effect on surgical planning. We describe a case in which two vascular irregularities, an Arc of Buhler and celiac stenosis, were identified on angiogram after completion of a pancreaticoduodenectomy. While there could have been catastrophic results from his surgery in the setting of celiac stenosis, the presence of the aberrant Arc of Buhler allowed this patient to emerge without any permanent morbidity. PMID- 27200205 TI - Concurrent Occurrence of Tumor in Colon and Small Bowel following Intestinal Obstruction: A Case Report and Review of the Literature. AB - An intestinal obstruction occurs when either the small or large intestine is partly or completely blocked so it prevents passing the food or fluid through the small/large bowel. This blockage is due to the existence of a mechanical obstruction such as foreign material, mass, hernia, or volvulus. Common symptoms include cramping pain, nausea and vomiting, changes in bowel habits, inability to pass stool, and lack of gas. We present a case of an 83-year-old man who had been referred to Taleghani Hospital with symptoms of bowel obstruction. He underwent the surgery. The findings of exploration of the entire abdomen showed two types of mass separately in two different organs. In postoperative workup, pathology reported two types of tumors (adenocarcinoma and neuroendocrine tumors). PMID- 27200206 TI - The Modification Effect of Influenza Vaccine on Prognostic Indicators for Cardiovascular Events after Acute Coronary Syndrome: Observations from an Influenza Vaccination Trial. AB - Introduction. The prognosis of acute coronary syndrome (ACS) patients has been improved with several treatments such as antithrombotics, beta-blockers, and angiotensin-converting enzyme inhibitors (ACEI) as well as coronary revascularization. Influenza vaccination has been shown to reduce adverse outcomes in ACS, but no information exists regarding the interaction of other treatments. Methods. This study included 439 ACS patients from Phrommintikul et al. A single dose of inactivated influenza vaccine was given by intramuscular injection in the vaccination group. The cardiovascular outcomes were described as major cardiovascular events (MACEs) which included mortality, hospitalization due to ACS, and hospitalization due to heart failure (HF). The stratified and multivariable Cox's regression analysis was performed. Results. The stratified Cox's analysis by influenza vaccination for each cardiovascular outcome and discrimination of hazard ratios showed that beta-blockers had an interaction with influenza vaccination. Moreover, the multivariable hazard ratios disclosed that influenza vaccine is associated with a significant reduction of hospitalization due to HF in patients who received beta-blockers (HR = 0.05, 95% CI = 0.004-0.71, P = 0.027), after being adjusted for prognostic indicators (sex, dyslipidemia, serum creatinine, and left ventricular ejection fraction). Conclusions. The influenza vaccine was shown to significantly modify the effect of beta-blockers in ACS patients and to reduce the hospitalization due to HF. However, further study of a larger population and benefits to HF patients should be investigated. PMID- 27200207 TI - Assessment of the Potential Biological Activity of Low Molecular Weight Metabolites of Freshwater Macrophytes with QSAR. AB - The paper focuses on the assessment of the spectrum of biological activities (antineoplastic, anti-inflammatory, antifungal, and antibacterial) with PASS (Prediction of Activity Spectra for Substances) for the major components of three macrophytes widespread in the Holarctic species of freshwater, emergent macrophyte with floating leaves, Nuphar lutea (L.) Sm., and two species of submergent macrophyte groups, Ceratophyllum demersum L. and Potamogeton obtusifolius (Mert. et Koch), for the discovery of their ecological and pharmacological potential. The predicted probability of anti-inflammatory or antineoplastic activities above 0.8 was observed for twenty compounds. The same compounds were also characterized by high probability of antifungal and antibacterial activity. Six metabolites, namely, hexanal, pentadecanal, tetradecanoic acid, dibutyl phthalate, hexadecanoic acid, and manool, were a part of the major components of all three studied plants, indicating their high ecological significance and a certain universalism in their use by various species of water plants for the implementation of ecological and biochemical functions. This report underlines the role of identified compounds not only as important components in regulation of biochemical and metabolic pathways and processes in aquatic ecological systems, but also as potential pharmacological agents in the fight against different diseases. PMID- 27200208 TI - Appraisal of Chicken Production with Associated Biosecurity Practices in Commercial Poultry Farms Located in Jos, Nigeria. AB - A questionnaire-based study of chicken production system with on-farm biosecurity practices was carried out in commercial poultry farms located in Jos, Nigeria. Commercial and semicommercial farms had 75.3% and 24.5% of 95,393 birds on 80 farms, respectively. Farms using deep litter and battery cage systems were 69 (86.3%) and 10 (12.5%), respectively. In our biosecurity scoring system, a correct practice of each indicator of an event scored 1.00 and biosecurity score (BS) of each farm was the average of the scores of biosecurity indicators for the farm, giving BS of zero and 1.00 as absence of biosecurity and optimal biosecurity, respectively. Semicommercial farms had higher BS than commercial farms. The flock size did not significantly (p > 0.05) affect the mean BS. Disease outbreaks correlated (r = -0.97) with BS, showing a tendency of reduction of disease outbreaks with increasing BS. Outbreaks were significantly (p < 0.05) associated with deep litter system. In conclusion, the chicken production system requires increased drive for excellent biosecurity practices and weak points in the biosecurity could be ameliorated by extension of information to farmers in order to support expansion of chicken production with robust biosecurity measures that drastically reduce risk of disease outbreak. PMID- 27200209 TI - In Utero Nutritional Manipulation Provokes Dysregulated Adipocytokines Production in F1 Offspring in Rats. AB - Background. Intrauterine environment plays a pivotal role in the origin of fatal diseases such as diabetes. Diabetes and obesity are associated with low-grade inflammatory state and dysregulated adipokines production. This study aims to investigate the effect of maternal obesity and malnutrition on adipokines production (adiponectin, leptin, and TNF-alpha) in F1 offspring in rats. Materials and Methods. Wistar rats were allocated in groups: F1 offspring of control mothers under control diet (CF1-CD) and under high-fat diet (CF1-HCD), F1 offspring of obese mothers under CD (OF1-CD) and under HCD (OF1-HCD), and F1 offspring of malnourished mothers under CD (MF1-CD) and under HCD (MF1-HCD). Every 5 weeks postnatally, blood samples were obtained for biochemical analysis. Results. At the end of the 30-week follow-up, OF1-HCD and MF1-HCD exhibited hyperinsulinemia, moderate dyslipidemia, insulin resistance, and impaired glucose homeostasis compared to CF1-CD and CF1-HCD. OF1-HCD and MF1-HCD demonstrated low serum levels of adiponectin and high levels of leptin compared to CF1-CD and CF1 HCD. OF1-CD, OF1-HCD, and MF1-HCD had elevated serum levels of TNF-alpha compared to CF1-CD and CF1-HCD (p < 0.05). Conclusion. Maternal nutritional manipulation predisposes the offspring to development of insulin resistance in their adult life, probably via instigating dysregulated adipokines production. PMID- 27200210 TI - Can Impaired Elasticity of Aorta Predict the Success of Vardenafil Treatment in Patients with Erectile Dysfunction? AB - Objective. Vardenafil is used in treatment of erectile dysfunction (ED) but reveals variable clinical outcomes. Here, we aimed to evaluate the role of aortic elasticity in predicting vardenafil success among patients with ED. Methods. Sixty-one consecutive male subjects with primary ED and indication for vardenafil treatment were included. All subjects fulfilled 5-item version of the International Index of Erectile Function (IIEF-5) before the vardenafil treatment. Pretreatment aortic stiffness index (ASI) and aortic distensibility (AD) were obtained echocardiographically. Following two-month vardenafil treatment, the patients were reevaluated with IIEF-5. Pretreatment, posttreatment, and DeltaIIEF-5 scores and ASI values were compared. Results. Average age was 54 +/- 8 years. Pretreatment and posttreatment IIEF-5 and DeltaIIEF-5 scores were 9.1 +/- 2.5; 18.5 +/- 2.3; and 9.4 +/- 3, respectively. Mean ASI and AD values were 3.10 +/- 0.54 and 4.13 +/- 2.55 1/(10(3) * mmHg) accordingly. ASI value of severe pretreatment ED (n = 15) was significantly higher than that of mild-moderate pretreatment ED (n = 12) (p < 0.001). All pretreatment IIEF-5 scores increased significantly compared to posttreatment IIEF 5 scores (p < 0.001). ASI values were significantly correlated to pretreatment IIEF-5 scores (p < 0.001) and DeltaIIEF-5 value (p < 0.001) but not to posttreatment IIEF-5 score. Conclusion. Aortic elasticity was impaired in accordance with degree of ED. The subjects with higher ASI values obtained more benefits from vardenafil. PMID- 27200212 TI - Study on GIS Visualization in Evaluation of the Human Living Environment in Shenyang-Dalian Urban Agglomeration. AB - Analysis of human living environmental quality of Shenyang-Dalian urban agglomerations has important theoretical and practical significance in rapid development region. A lot of investigations have been carried for Shenyang-Dalian urban agglomerations, including 38 counties. Based on the carrying capacity of resources, natural and socioeconomic environmental factors and regional changes of human living environmental evaluation are analyzed with the application of geographic information systems (GIS) software. By using principal component analysis (PCA) model and natural breaks classification (NBC) method, the evaluation results are divided into five categories. The results show that the human living environmental evaluation (HLEE) indexes of Dalian, Shenyang, and Liaoyang are higher than other counties. Among these counties, the human living environmental evaluation (HLEE) indexes of coastal counties are significantly higher than inland counties. The range of the human living environmental evaluation index in most of the study area is at III, IV, and V levels, accounting for 80.01%. Based on these results, it could illustrate the human living environment is in relatively suitable condition in Shenyang-Dalian urban agglomeration. PMID- 27200211 TI - Modulation of Drug Resistance in Staphylococcus aureus with Coumarin Derivatives. AB - Semisynthetic and commercial coumarins were investigated for their antibacterial and adjuvant properties with antibiotic agents against norfloxacin, erythromycin, and tetracycline resistant Staphylococcus aureus as based on efflux mechanisms. The coumarins and certain commercial antibiotics had their Minimum Inhibitory Concentrations determined by broth microdilution assay against resistant S. aureus strains which overexpress efflux pump proteins. For evaluation of the modulatory activity, the antibiotics MICs were determined in the presence of the coumarin derivatives at subinhibitory concentration. Although the coumarins did not display relevant antibacterial activity (MIC >= 128 ug/mL), they did modulate the antibiotics activities. Various coumarins, especially the alkylated derivatives in combination with antibiotics at subinhibitory concentrations, modulated antibiotic activity, reducing the MIC for tetracycline and norfloxacin by 2 to 8 times. Polar Surface Area (PSA) studies were performed and the fact that the presence of apolar groups is an important factor for the modulatory activity of coumarins was corroborated. Docking on the Penicillin-Binding Protein from MRSA identified that 18 is a potential ligand presenting low E binding. The results indicate that coumarin derivatives modulated antibiotic resistance and may be used as potential antibiotic adjuvants, acting by bacterial efflux pump inhibition in S. aureus. PMID- 27200213 TI - Effects of Cadmium and Zinc on the Gamete Viability, Fertilization, and Embryonic Development of Tripneustes gratilla (Linnaeus). AB - Heavy metals are frequently reported for their mutagenic and teratogenic effects on benthic organisms. Thus, this study aimed to determine the toxicity of cadmium (Cd) and zinc (Zn) in the gametes of T. gratilla and to compare its fertilization and embryonic development under the highest nongametotoxic concentrations of these heavy metals. Gamete viability of T. gratilla under CdCl2 and ZnSO4 treatments was assayed through resazurin reduction test (RRT) and was confirmed through gamete morphology assay. ZnSO4 was more toxic to T. gratilla gametes than CdCl2 and egg cells were more sensitive to both than the sperm cells. Higher concentrations of CdCl2 and ZnSO4 induced gamete apoptosis and necrosis while highest nongametotoxic concentrations were determined at 1 * 10(-3) M and 1 * 10( 4) M, respectively, and were used in an in vitro fertilization and embryonic development experiment. ZnSO4 treatment inhibited fertilization more than CdCl2 and yielded more deformed embryos, while both induced abnormalities and hindered further embryonic development. This study gives the first report on the specific concentrations of Cd and Zn that are toxic to T. gratilla gametes and has confirmed the teratogenic effects of these heavy metals. PMID- 27200214 TI - Steps We Have Taken and Steps We Must Take. PMID- 27200215 TI - Effects of a Combined Exercise Program Using an iPad for Older Adults. AB - OBJECTIVES: The purpose of this study was to examine the function, health status, and efficacy effects of a combined exercise program using an iPad among older women in Korea, a tech-savvy country. METHODS: The study employed a pretest and posttest experimental design with a control group. The experimental group of subjects comprised 16 female older adults and the control group comprised 10 who were aged 65 years or older. The experimental group participated in a supervised group-based exercise program and an individualized home-based exercise program that involved the use of an iPad. The combined group and home-based exercise program consisted of group exercise, which took place in a senior center for 30 minutes weekly, and a home-based iPad exercise program, which the subjects followed at least 3 times a week. The collected data were analyzed using the Statistical Analysis System (SAS ver. 9.3 TS Level 1M0) program, which utilized a chi-square test, a Fisher exact test, a t-test, and a repeated-measures ANOVA. RESULTS: The results showed that cognitive status changed significantly over time, and there was an interaction between group and time. Further, self-efficacy for exercise and outcome expectations for exercise changed significantly over time. CONCLUSIONS: Exercise programs using iPad interventions may be useful for the management of cognitive functioning and the integration of functional physical abilities in older adults. PMID- 27200216 TI - Utilization and Content Evaluation of Mobile Applications for Pregnancy, Birth, and Child Care. AB - OBJECTIVES: The purpose of this study was to explore the use of mobile applications about pregnancy, birth, and child care among pregnant women and to review the characteristics, contents, and credibility of the applications used by these women. METHODS: This study was cross-sectional and was conducted using a survey method. One hundred and ninety-three pregnant women participated in this study. The questionnaire was developed to examine the pattern and reasons for pregnancy-related application usage. The 47 mobile apps used by participants were reviewed and categorized based on functions and developers. The credibility of the information provided by the mobile applications was evaluated using a structured measurement. RESULTS: Fifty-five percent of the participants were using mobile apps related to pregnancy, birth, and/or child care. First-time mothers used the apps significantly more often than women who were pregnant for the second time. Women who had used a smartphone for a longer period of time were more likely to use apps related to pregnancy, birth, and/or child care. The most frequently-used information concerned signs of risk and disease during pregnancy. Experts' quick opinions and Q&A formats related to diet and medication administration during pregnancy were the women's most cited need for content in applications. Information was the most common function of the apps. In the evaluation of information credibility, the 'information source' category had the lowest score. CONCLUSIONS: The results showed that applications related to pregnancy, birth, and child care have become an important information source for pregnant women. To fulfill the needs of users, credible applications related to pregnancy, birth, and child care should be developed and managed by qualified healthcare professionals. PMID- 27200217 TI - GEE: An Informatics Tool for Gene Expression Data Explore. AB - OBJECTIVES: Major public high-throughput functional genomic data repositories, including the Gene Expression Omnibus (GEO) and ArrayExpress have rapidly expanded. As a result, a large number of diverse high-throughput functional genomic data retrieval systems have been developed. However, high-throughput functional genomic data retrieval remains challenging. METHODS: We developed Gene Expression data Explore (GEE), the first powerful, flexible web and mobile search application for searching whole-genome epigenetic data and microarray data in public databases, such as GEO and ArrayExpress. RESULTS: GEE provides an elaborate, convenient interface of query generation competences not available via various high-throughput functional genomic data retrieval systems, including GEO, ArrayExpress, and Atlas. In particular, GEE provides a suitable query generator using eVOC, the Experimental Factor Ontology (EFO), which is well represented with a variety of high-throughput functional genomic data experimental conditions. In addition, GEE provides an experimental design query constructor (EDQC), which provides elaborate retrieval filter conditions when the user designs real experiments. CONCLUSIONS: The web version of GEE is available at http://www.snubi.org/software/gee, and its app version is available from the Apple App Store. PMID- 27200218 TI - Nomogram of Naive Bayesian Model for Recurrence Prediction of Breast Cancer. AB - OBJECTIVES: Breast cancer has a high rate of recurrence, resulting in the need for aggressive treatment and close follow-up. However, previously established classification guidelines, based on expert panels or regression models, are controversial. Prediction models based on machine learning show excellent performance, but they are not widely used because they cannot explain their decisions and cannot be presented on paper in the way that knowledge is customarily represented in the clinical world. The principal objective of this study was to develop a nomogram based on a naive Bayesian model for the prediction of breast cancer recurrence within 5 years after breast cancer surgery. METHODS: The nomogram can provide a visual explanation of the predicted probabilities on a sheet of paper. We used a data set from a Korean tertiary teaching hospital of 679 patients who had undergone breast cancer surgery between 1994 and 2002. Seven prognostic factors were selected as independent variables for the model. RESULTS: The accuracy was 80%, and the area under the receiver operating characteristics curve (AUC) of the model was 0.81. CONCLUSIONS: The nomogram can be easily used in daily practice to aid physicians and patients in making appropriate treatment decisions after breast cancer surgery. PMID- 27200219 TI - Comparison of Predictive Models for the Early Diagnosis of Diabetes. AB - OBJECTIVES: This study develops neural network models to improve the prediction of diabetes using clinical and lifestyle characteristics. Prediction models were developed using a combination of approaches and concepts. METHODS: We used memetic algorithms to update weights and to improve prediction accuracy of models. In the first step, the optimum amount for neural network parameters such as momentum rate, transfer function, and error function were obtained through trial and error and based on the results of previous studies. In the second step, optimum parameters were applied to memetic algorithms in order to improve the accuracy of prediction. This preliminary analysis showed that the accuracy of neural networks is 88%. In the third step, the accuracy of neural network models was improved using a memetic algorithm and resulted model was compared with a logistic regression model using a confusion matrix and receiver operating characteristic curve (ROC). RESULTS: The memetic algorithm improved the accuracy from 88.0% to 93.2%. We also found that memetic algorithm had a higher accuracy than the model from the genetic algorithm and a regression model. Among models, the regression model has the least accuracy. For the memetic algorithm model the amount of sensitivity, specificity, positive predictive value, negative predictive value, and ROC are 96.2, 95.3, 93.8, 92.4, and 0.958 respectively. CONCLUSIONS: The results of this study provide a basis to design a Decision Support System for risk management and planning of care for individuals at risk of diabetes. PMID- 27200220 TI - Association of EMR Adoption with Minority Health Care Outcome Disparities in US Hospitals. AB - OBJECTIVES: Disparities in healthcare among minority groups can result in disparate treatments for similar severities of symptoms, unequal access to medical care, and a wide deviation in health outcomes. Such racial disparities may be reduced via use of an Electronic Medical Record (EMR) system. However, there has been little research investigating the impact of EMR systems on the disparities in health outcomes among minority groups. METHODS: This study examined the impact of EMR systems on the following four outcomes of black patients: length of stay, inpatient mortality rate, 30-day mortality rate, and 30 day readmission rate, using patient and hospital data from the Medicare Provider Analysis and Review and the Healthcare Information and Management Systems Society between 2000 and 2007. The difference-in-difference research method was employed with a generalized linear model to examine the association of EMR adoption on health outcomes for minority patients while controlling for patient and hospital characteristics. RESULTS: We examined the association between EMR adoption and the outcomes of minority patients, specifically black patients. However, after controlling for patient and hospital characteristics we could not find any significant changes in the four health outcomes of minority patients before and after EMR implementation. CONCLUSIONS: EMR systems have been reported to support better coordinated care, thus encouraging appropriate treatment for minority patients by removing potential sources of bias from providers. Also, EMR systems may improve the quality of care provided to patients via increased responsiveness to care processes that are required to be more time-sensitive and through improved communication. However, we did not find any significant benefit for minority groups after EMR adoption. PMID- 27200221 TI - Auditing Knowledge toward Leveraging Organizational IQ in Healthcare Organizations. AB - OBJECTIVES: In this study, a knowledge audit was conducted based on organizational intelligence quotient (OIQ) principles of Iran's Ministry of Health and Medical Education (MOHME) to determine levers that can enhance OIQ in healthcare. METHODS: The mixed method study was conducted within the MOHME. The study population consisted of 15 senior managers and policymakers. A tool based on literature review and panel expert opinions was developed to perform a knowledge audit. RESULTS: The significant results of this auditing revealed the following: lack of defined standard processes for organizing knowledge management (KM), lack of a knowledge map, absence of a trustee to implement KM, absence of specialists to produce a knowledge map, individuals' unwillingness to share knowledge, implicitness of knowledge format, occasional nature of knowledge documentation for repeated use, lack of a mechanism to determine repetitive tasks, lack of a reward system for the formation of communities, groups and networks, non-updatedness of the available knowledge, and absence of commercial knowledge. CONCLUSIONS: The analysis of the audit findings revealed that three levers for enhancing OIQ, including structure and process, organizational culture, and information technology must be created or modified. PMID- 27200222 TI - Functional Profiling of Human MeCP2 by Automated Data Comparison Analysis and Computerized Expression Pathway Modeling. AB - OBJECTIVES: Methyl-CpG binding protein 2 (MeCP2) is a ubiquitous epigenetic factor that represses gene expression by modifying chromatin. Mutations in the MeCP2 gene cause Rett syndrome, a progressive neurodevelopmental disorder. Recent studies also have shown that MeCP2 plays a role in carcinogenesis. Specifically, functional ablation of MeCP2 suppresses cell growth and leads to the proliferation of cancer cells. However, MeCP2's function in adult tissues remains poorly understood. We utilized a weight matrix-based comparison software to identify transcription factor binding site (TFBS) of MeCP2-regulated genes, which were recognized by cDNA microarray analysis. METHODS: MeCP2 expression was silenced using annealed siRNA in HEK293 cells, and then a cDNA microarray analysis was performed. Functional analysis was carried out, and transcriptional levels in target genes regulated by MeCP2 were investigated. TFBS analysis was done within genes selected by the cDNA microarray analysis, using a weight matrix based program and the TRANSFAC 6.0 database. RESULTS: Among the differentially expressed genes with a change in expression greater than two-fold, 189 genes were up-regulated and 91 genes were down-regulated. Genes related to apoptosis and cell proliferation (JUN, FOSL2, CYR61, SKIL, ATF3, BMABI, BMPR2, RERE, and FALZ) were highly up-regulated. Genes with anti-apoptotic and anti-proliferative functions (HNRPA0, HIS1, and FOXC1) were down-regulated. Using TFBS analysis within putative promoters of novel candidate target genes of MeCP2, disease related transcription factors were identified. CONCLUSIONS: The present results provide insights into the new target genes regulated by MeCP2 under epigenetic control. This information will be valuable for further studies aimed at clarifying the pathogenesis of Rett syndrome and neoplastic diseases. PMID- 27200223 TI - Development of an Integrated Biospecimen Database among the Regional Biobanks in Korea. AB - OBJECTIVES: This study developed an integrated database for 15 regional biobanks that provides large quantities of high-quality bio-data to researchers to be used for the prevention of disease, for the development of personalized medicines, and in genetics studies. METHODS: We collected raw data, managed independently by 15 regional biobanks, for database modeling and analyzed and defined the metadata of the items. We also built a three-step (high, middle, and low) classification system for classifying the item concepts based on the metadata. To generate clear meanings of the items, clinical items were defined using the Systematized Nomenclature of Medicine Clinical Terms, and specimen items were defined using the Logical Observation Identifiers Names and Codes. To optimize database performance, we set up a multi-column index based on the classification system and the international standard code. RESULTS: As a result of subdividing 7,197,252 raw data items collected, we refined the metadata into 1,796 clinical items and 1,792 specimen items. The classification system consists of 15 high, 163 middle, and 3,588 low class items. International standard codes were linked to 69.9% of the clinical items and 71.7% of the specimen items. The database consists of 18 tables based on a table from MySQL Server 5.6. As a result of the performance evaluation, the multi-column index shortened query time by as much as nine times. CONCLUSIONS: The database developed was based on an international standard terminology system, providing an infrastructure that can integrate the 7,197,252 raw data items managed by the 15 regional biobanks. In particular, it resolved the inevitable interoperability issues in the exchange of information among the biobanks, and provided a solution to the synonym problem, which arises when the same concept is expressed in a variety of ways. PMID- 27200224 TI - Current Status of Nursing Informatics Education in Korea. AB - OBJECTIVES: This study presents the current status of nursing informatics education, the content covered in nursing informatics courses, the faculty efficacy, and the barriers to and additional supports for teaching nursing informatics in Korea. METHODS: A set of questionnaires consisting of an 18-item questionnaire for nursing informatics education, a 6-item questionnaire for faculty efficacy, and 2 open-ended questions for barriers and additional supports were sent to 204 nursing schools via email and the postal service. Nursing schools offering nursing informatics were further asked to send their syllabuses. The subjects taught were analyzed using nursing informatics competency categories and other responses were tailed using descriptive statistics. RESULTS: A total of 72 schools (35.3%) responded to the survey, of which 38 reported that they offered nursing informatics courses in their undergraduate nursing programs. Nursing informatics courses at 11 schools were taught by a professor with a degree majoring in nursing informatics. Computer technology was the most frequently taught subject (27 schools), followed by information systems used for practice (25 schools). The faculty efficacy was 3.76 +/- 0.86 (out of 5). The most frequently reported barrier to teaching nursing informatics (n = 9) was lack of awareness of the importance of nursing informatics. Training and educational opportunities was the most requested additional support. CONCLUSIONS: Nursing informatics education has increased during the last decade in Korea. However, the proportions of faculty with degrees in nursing informatics and number of schools offering nursing informatics courses have not increased much. Thus, a greater focus is needed on training faculty and developing the courses. PMID- 27200227 TI - Are Postgraduate Medical Residency Training Positions in Atlantic Canada Evenly Distributed? AB - Background The distribution of postgraduate medical training (residency) positions in Canada is administered by medical schools and universities in conjunction with individual provinces. In Atlantic Canada, the Maritime provinces are considered a single unit under Dalhousie University in Nova Scotia (NS), although distributed medical undergraduate education through Dalhousie and Sherbrooke has enabled medical students to complete their entire course of study in New Brunswick (NB). It is unclear if postgraduate medical education has been distributed in a similar fashion in Atlantic Canada, particularly in New Brunswick and Prince Edward Island (PE). Methods Data on the number of R1 residency positions was obtained from the Canadian Resident Matching Service (CaRMS) database. The distribution of R1 positions was described and compared nationally and through the Atlantic provinces. The analysis was completed using MS Excel and Prism. Results Rates of R1 positions per million persons varied widely; the national median rate was 97 positions per million persons, with a range of 34 to 138. The combined Maritime provinces rate of R1 positions was 71 per million persons and the rate in Newfoundland (NL) was 138 positions per million. The NS rate was 106 positions per million while the NB rate was 54 per million and the PE rate 34 per million. Sixty-four percent of all residency training positions in Atlantic Canada were based in the two most urban areas of Halifax, NS or St John's, NL. Royal College (specialty) positions were more likely to be based at the main university campus city than family medicine training positions (97 vs. 3%; 33 vs. 67%, respectively). Conclusion There is a high level of variation in available residency positions among the individual provinces, especially in Atlantic Canada. The lower prevalence of opportunities in NB and PE may influence the ability of these provinces to recruit and retain new physicians. PMID- 27200226 TI - Anterior Cervical Discectomy and Fusion (ACDF): Comparison Between Zero Profile Implants and Anterior Cervical Plate and Spacer. AB - INTRODUCTION: Interposition grafts combined with anterior plating currently remain the gold standard for anterior cervical discectomy and fusion. The use of anterior plates increases fusion rates but may be associated with higher rates of postoperative dysphagia. The aim of the current study was to determine the clinical and radiological outcomes following anterior cervical discectomy and fusion (ACDF) using zero-profile anchored spacers versus standard interposition grafts with anterior plating. METHODS: This was a retrospective case series. A total of 53 male and 51 female consecutive patients (164 total operated levels) who underwent ACDF between 2007 and 2011 were included. The mean clinical follow up was 15.7 +/- 1.2 (SEM) months for patients with zero-profile implants and 14.8 +/- 2.1 months for patients with conventional ACDF with anterior plating. Patient demographics, operative details, clinical outcomes, complications, and radiographic imaging were reviewed. Dysphagia was determined using the Bazaz criteria. RESULTS: Clinical outcome scores improved in both groups as measured by the modified Japanese Orthopedic Association and Nurick scores. Zero-profile constructs gave rise to significantly less prevertebral soft tissue swelling compared to constructs with anterior plates postoperatively (15.74 +/- 0.52 as compared to 20.48 +/- 0.85 mm, p < 0.001) and at the latest follow-up (10.88 +/- 0.39 mm vs. 13.72 +/- 0.67 mm, p < 0.001). There was a significant difference in the incidence of dysphagia at the latest follow-up (1.5% vs. 20%, p=0.001, zero profile vs. anterior plate, respectively). CONCLUSION: Zero-profile implants lead to functional outcomes similar to standard anterior plate constructs. Avoiding the use of an anterior locking plate may decrease the risk of persistent postoperative dysphagia. PMID- 27200228 TI - Nipple Is Not Elevated with Breast Augmentation. PMID- 27200229 TI - Body Contouring: The Success of the Androgynous Model. PMID- 27200225 TI - Design, Synthesis, and Chemical and Biological Properties of Cyclic ADP-4 Thioribose as a Stable Equivalent of Cyclic ADP-Ribose. AB - Here we describe the successful synthesis of cyclic ADP-4-thioribose (cADPtR, 3), designed as a stable mimic of cyclic ADP-ribose (cADPR, 1), a Ca2+-mobilizing second messenger, in which the key N1-beta-thioribosyladenosine structure was stereoselectively constructed by condensation between the imidazole nucleoside derivative 8 and the 4-thioribosylamine 7 via equilibrium in 7 between the alpha anomer (7alpha) and the beta-anomer (7beta) during the reaction course. cADPtR is, unlike cADPR, chemically and biologically stable, while it effectively mobilizes intracellular Ca2+ like cADPR in various biological systems, such as sea urchin homogenate, NG108-15 neuronal cells, and Jurkat T-lymphocytes. Thus, cADPtR is a stable equivalent of cADPR, which can be useful as a biological tool for investigating cADPR-mediated Ca2+-mobilizing pathways. PMID- 27200230 TI - Masseteric Nerve as "Baby Sitter" Procedure in Incomplete Facial Paralysis. AB - Supplemental Digital Content is available in the text. PMID- 27200231 TI - Combined Use of the Latissimus Dorsi Musculocutaneous Flap and the Anterolateral Thigh Flap to Reconstruct an Extensive Shoulder Defect in an NF-1 Patient. AB - Soft tissue coverage after the resection of a large malignant peripheral neural sheath tumor (MPNST) is a challenge. We report the successful reconstruction of an extensive shoulder defect after MPNST resection in a patient with a type 1 neurofibromatosis with a novel combination of flaps. A 70-year-old man with type 1 neurofibromatosis presented with a recurrent MPNST on his right shoulder. He underwent a wide excision of the tumor, which resulted in a huge soft tissue defect around the shoulder joint. The resultant defect was reconstructed with a pedicled latissimus dorsi musculocutaneous flap and a free anterolateral thigh flap. The flaps survived, and the wounds healed uneventfully. His affected arm was useful. The combination of a pedicled latissimus dorsi musculocutaneous flap and a free anterolateral thigh flap is a versatile option for the reconstruction of an extensive shoulder defect. PMID- 27200232 TI - Scalp Medical Tattooing Technique to Camouflage Bifid Parietal Whorls. AB - BACKGROUND: To the best of the authors' knowledge, no reports have described cosmetic problems arising from the hair direction around the parietal whorl (PW). This study was performed to evaluate the efficacy of scalp medical tattooing technique for camouflaging bifid PWs. METHODS: We retrospectively examined the outcomes of scalp medical tattooing in 38 patients who were admitted for camouflage of a bifid PW. RESULTS: All patients' cosmetic appearance was judged, by both the patients and the surgeon, to be markedly improved. No specific complications occurred, such as infection, hair loss in the operative field, or other problems. CONCLUSION: Scalp medical tattooing appears to be an effective method that helps to camouflage the see-through appearance of bifid PWs. PMID- 27200233 TI - 30-year International Pediatric Craniofacial Surgery Partnership: Evolution from the "Third World" Forward. AB - BACKGROUND: Craniofacial diseases constitute an important component of the surgical disease burden in low- and middle-income countries. The consideration to introduce craniofacial surgery into such settings poses different questions, risks, and challenges compared with cleft or other forms of plastic surgery. We report the evolution, innovations, and challenges of a 30-year international craniofacial surgery partnership. METHODS: We retrospectively report a partnership between surgeons at the Uniwersytecki Szpital Dzieciecy in Krakow, Poland, and a North American craniofacial surgeon. We studied patient conditions, treatment patterns, and associated complications, as well as program advancements and limitations as perceived by surgeons, patient families, and hospital administrators. RESULTS: Since partnership inception in 1986, the complexity of cases performed increased gradually, with the first intracranial case performed in 1995. In the most recent 10-year period (2006-2015), 85 patients have been evaluated, with most common diagnoses of Apert syndrome, Crouzon syndrome, and single-suture craniosynostosis. In the same period, 55 major surgical procedures have been undertaken, with LeFort III midface distraction, posterior vault distraction, and frontoorbital advancement performed most frequently. Key innovations have been the employment of craniofacial distraction osteogenesis, the use of Internet communication and digital photography, and increased understanding of how craniofacial morphology may improve in the absence of surgical intervention. Ongoing challenges include prohibitive training pathways for pediatric plastic surgeons, difficulty in coordinating care with surgeons in other institutions, and limited medical and material resources. CONCLUSION: Safe craniofacial surgery can be introduced and sustained in a resource-limited setting through an international partnership. PMID- 27200234 TI - No-drain DIEP Flap Donor-site Closure Using Barbed Progressive Tension Sutures. AB - BACKGROUND: The use of progressive tension sutures has been shown to be comparable to the use of abdominal drains in abdominoplasty. However, the use of barbed progressive tension sutures (B-PTSs) in deep inferior epigastric artery perforator (DIEP) flap donor-site closure has not been investigated. METHODS: A retrospective chart review was performed on patients with DIEP flap reconstruction in a 3-year period at 2 institutions by 2 surgeons. Patients were compared by method of DIEP donor-site closure. Group 1 had barbed running progressive tension sutures without drain placement. Group 2 had interrupted progressive tension closure with abdominal drain placement (PTS-AD). Group 3 had closure with only abdominal drain placement (AD). Data collected included demographics, perioperative data, and postoperative outcomes. RESULTS: Seventy five patients underwent DIEP reconstruction (25 B-PTS, 25 PTS-AD, and 25 AD). Patient characteristics-age, body mass index, comorbidities, smoking status, and chemotherapy-were not significantly different between groups. Rate of seroma was 1.3% (B-PTS = 0%, PTS-AD = 4%, AD = 0%), wound dehiscence 16% (B-PTS = 8%, PTS-AD = 16%, AD = 24%), and umbilical necrosis 5.3% (B-PTS = 0%, PTS-AD = 0%, AD = 16%). No hematomas were observed in any patients. No statistically significant difference was found between complication rates across groups. CONCLUSIONS: Use of B-PTSs for abdominal closure after DIEP flap harvest can obviate the need for abdominal drains. Complication rates following this technique are not significantly different from closure using progressive tension suture and abdominal drain placement. This practice can prevent the use of abdominal drains, which can promote patient mobility, increase independence upon discharge, and contribute to patient satisfaction. PMID- 27200235 TI - Unusual Vascular Supply to Extensor Digitorum Brevis. AB - Lower limb reconstruction after a traumatic event has always been a challenge for plastic surgeons. The reliability of vessel integrity postinjury often drives us away from a local reconstructive option. With the advancement of computed tomography angiogram, it can not only demonstrate the continuation of major vessels but also helps to map the vascular supply at a perforator level. We hereby report an incidentally identified anatomical variant with dual dominant blood supply to the extensor digitorum brevis muscle from an extra branch of anterior tibial artery originated at midtibial level. This variant was picked up preoperatively by computed tomography angiogram and confirmed intraoperatively to be one of the dominant supply. We took advantage of this unusual anatomy by basing our reconstruction on this branch and hence spared the need to terminalize distal dorsalis pedis artery. PMID- 27200236 TI - Pigmented Villonodular Synovitis of the Temporomandibular Joint: A Unique Presentation. AB - Pigmented villonodular synovitis (PVNS) is a rare and benign proliferative disorder of synovium with potentially locally aggressive growth and invasion of the bone. Occurring within the joints, tendon sheaths, and bursae, it is most commonly a monoarticular disease affecting large joints. In particular, most cases of PVNS occur in the knee. PVNS of the temporomandibular joint (TMJ) is a highly rare disorder, with approximately 60 cases reported. Herein, we present a unique case of an elderly male presenting with ear pain and subsequently diagnosed with PVNS of the TMJ with a history of trauma to the area. Initial imaging of the TMJ and the surrounding region looked concerning for invasive and/or malignant disease, but an open biopsy confirmed PVNS. PMID- 27200237 TI - Lateral Approach to the Popliteal Artery for Free Tissue Transfer to the Lower Extremity. AB - Free tissue transfer to the proximal leg and knee requires appropriate recipient vessel selection. The popliteal vessels have historically been unpopular choices, due to their remote location often necessitating vein grafts, and need for prone positioning. In this report, we describe a lateral approach to the above-knee popliteal vessels, which was utilized for 2 cases of free tissue transfer to the lower extremity. Neither prone positioning nor vein grafts were needed. The lateral approach to the above-knee popliteal vessels and their branches is a viable option for the otherwise recipient vessel-depleted lower extremity. PMID- 27200238 TI - Orthognathic Consequences of Sphincter Pharyngoplasty in Cleft Patients: A 2 Institutional Study. AB - BACKGROUND: Understanding long-term sequelae of cleft treatment is paramount in the refinement of treatment algorithms to accomplish optimized immediate and long term outcomes. In this study, we reviewed sphincter pharyngoplasties as a method of velopharyngeal insufficiency (VPI) treatment in relationship to orthognathic surgery. METHODS: Cleft lip/palate and cleft palate patients, 15 years of age and older, were reviewed for demographics, VPI surgery, revisions, and subsequent orthognathic surgery at 2 institutions. Chi-square test, Student's t test, and logistic regression analyses were performed. RESULTS: In 214 patients reviewed (mean age, 19.5 years), 61.7% were male, 18.2% had isolated cleft palate, 61.2% had unilateral cleft lip and palate, and 20.6% had bilateral cleft lip and palate. A total of 33.6% were diagnosed with VPI and received a sphincter pharyngoplasty (mean age, 11.9 years). When subsequent orthognathic surgery was examined, sphincter pharyngoplasty was not associated with maxillary advancement (P = 0.59) but did correlate with an increase in mandibular surgery from 2.8% to 11.1% (P = 0.02). The indications for mandibular surgery in the pharyngoplasty population were related to congenital micrognathia. When cephalometric analyses were evaluated, sphincter pharyngoplasty resulted in a decreased sella-to-nasion to-B point angle (mean, 79.0-76.3 degrees, P = 0.02) and a higher incidence of normal to class II maxillomandibular relationships as defined by A point-to nasion-to-B point angles >0.5 (P = 0.02). CONCLUSIONS: Sphincter pharyngoplasty decreases anterior mandibular growth and the discrepancy between maxillomandibular skeletal relationships because of the frequent predisposition of cleft patients to maxillary hypoplasia. In patients with congenital mandibular micrognathia, a small increase in mandibular surgeries may occur. PMID- 27200239 TI - Comparison of Shear-Wave and Strain Ultrasound Elastography for Evaluating Fat Induration after Breast Reconstruction. PMID- 27200240 TI - Decompression-Avulsion of the Auriculotemporal Nerve for Treatment of Migraines and Chronic Headaches. AB - Surgical decompression of peripheral branches of the trigeminal and occipital nerves has been shown to alleviate migraine symptoms. Site II surgery involves decompression of the zygomaticotemporal branch of the trigeminal nerve by the technique developed by Guyuron. Failure of site II surgery may occur secondary to an inability to recognize a second temporal trigger: site V, the auriculotemporal nerve. A direct approach for site V has been used with no clear description in the literature. Herein, we describe a safe and efficient method for auriculotemporal nerve decompression during the Guyuron endoscopic approach. Close attention to all temporal sites is necessary to avoid potential failure of migraine decompression surgery. PMID- 27200242 TI - Hyperbaric Oxygen following Bilateral Skin-sparing Mastectomies: A Case Report. AB - We describe a case in which hyperbaric oxygen therapy was used to salvage ischemic skin flaps after nipple-sparing mastectomy. PMID- 27200241 TI - The BODY-Q: A Patient-Reported Outcome Instrument for Weight Loss and Body Contouring Treatments. AB - BACKGROUND: Body contouring performed for cosmetic purposes, or after weight loss, has the potential to improve body image and health-related quality of life (HRQL). The BODY-Q is a new patient-reported outcome (PRO) instrument designed to measure patient perceptions of weight loss and/or body contouring. In this article, we describe the psychometric properties of the BODY-Q scales after an international field-test. METHODS: Weight loss and body contouring patients from Canada, United States, and United Kingdom were recruited between November 2013 and February 2015. Data were collected using an iPad directly into a web-based application or a questionnaire booklet. Rasch measurement theory analysis was used for item reduction and to examine reliability, validity, and ability to detect change. RESULTS: The sample included 403 weight loss and 331 body contouring patients. Most BODY-Q items had ordered thresholds (134/138) and good item fit. Scale reliability was acceptable, ie, Person separation index >0.70 for 16 scales, Cronbach alpha >=0.90 for 18 of 18 scales, and Test-retest >=0.87 for 17 of 18 scales. Appearance and HRQL scores were lower in participants with more obesity-related symptoms, higher body mass index, and more excess skin and in those pre- versus postoperative body contouring. The 134 weight loss patients who completed the BODY-Q twice, either 6 weeks (weight loss/nonsurgical body contouring program) or 6 months (bariatric program) later, improved significantly on 7 appearance and 4 HRQL scales. CONCLUSION: The BODY-Q is a clinically meaningful and scientifically sound patient-reported outcome instrument that can be used to measure outcomes in patients who undergo weight loss and/or body contouring. PMID- 27200243 TI - Chen's Double Eyelid Fold Ratio. AB - BACKGROUND: Double eyelidplasty can construct palpebral folds and enhance beauty perception for Asians with single eyelids. A new palpebral parameter for the quantitative interpretation of surgical outcomes is proposed on the basis of a photometric study of the altered proportions of Asian eyes after double eyelid operation. METHODS: A total of 100 Asian adults with single upper eyelids who were satisfied with the enlarged eyes by operation were included in the study. A retrospective measurement of palpebral parameters in the frontal profile both preoperatively and 6 months postoperatively was performed. The proportions of various parameters in the eyebrow-eye aesthetic unit were calculated and analyzed. RESULTS: Double eyelidplasty can augment the vertical dimension of palpebral fissure by 27.9% increase on average. The vertical ratio of palpebral fissure to the eyebrow-eye unit is augmented by 34.4% increase. The vertical ratio of the subunit below double eyelid fold peak to the unit is augmented by 82.6% increase. CONCLUSIONS: Double eyelidplasty can substantially enlarge the vertical dimensions of the eyes of Asians with single eyelids. The eyes are perceived to be larger because of the visually assimilated illusion of the superimposed eyelid fold and the relative proportions of the eyebrow-eye unit. The authors propose using a vertical ratio of the subunit below double eyelid fold peak in the eyebrow-eye unit to measure the visually perceived proportion of the eye in the unit. This ratio can be applied clinically for a quantitative evaluation of the surgical outcome after double eyelidplasty. PMID- 27200244 TI - Extracorporeal Free Flap Perfusion in Case of Prolonged Ischemia Time. AB - In free flap surgery, a clinically established concept still has to be found for the reduction of ischemia-related cell damage in the case of prolonged ischemia. Although promising results using extracorporeal free flap perfusion in the laboratory have been published in the past, until now this concept has not yet paved its way into clinical routine. This might be due to the complexity of perfusion systems and a lack of standardized tools. Here, we want to present the results of the first extracorporeal free flap perfusion in a clinical setting using a simple approach without the application of a complex perfusion machinery. PMID- 27200245 TI - Serious Vascular Complications after Nonsurgical Rhinoplasty: A Case Report. AB - There has been an increased global demand for dermal filler injections in recent years. Although hyaluronic acid-based dermal fillers generally have a good safety profile, serious vascular complications have been reported. Here we present a typical case of skin necrosis following a nonsurgical rhinoplasty using hyaluronic acid filler. Despite various rescuing managements, unsightly superficial scars were left. It is critical for plastic surgeons and dermatologists to be familiar with the vascular anatomy and the staging of vascular complications. Any patients suspected to experience a vascular complication should receive early management under close monitoring. Meanwhile, the potentially devastating outcome caused by illegal practice calls for stricter regulations and law enforcement. PMID- 27200246 TI - A 15-year-old Girl with an Asymmetric Hemitruncal Fat Distribution: Hemihyperthrophy or Hemiatrophy? AB - A 15-year-old girl presented to the pediatrician with complaints of excessive fat distribution on the right side and breast asymmetry. At age 2, she had undergone a left-sided nephrectomy because of a stage III Wilms tumor using a transverse cut supraumbilical approach, followed by systemic chemotherapy and local radiotherapy. In the case of trunk asymmetry, it is questionable which side is deviant. The asymmetry may be an expression of isolated hemihyperthrophy, syndromal hemihypertrophy related to the Wilms tumor, or an expression of left sided hemiatrophy as a late consequence of radiotherapy, chemotherapy, or surgery. Late clinical manifestations of childhood cancer treatment are difficult to distinguish from other independent diseases but must be considered as explanations for new onset of symptoms in adolescents. PMID- 27200247 TI - Blepharoplasty with a Buried Double Twisted Suture Technique to Correct Upper Eyelid Epiblepharon. AB - BACKGROUND: The authors evaluated the clinical efficacy of blepharoplasty using a newly developed, buried double twisted suture (BDTS) technique to correct upper eyelid epiblepharon. METHODS: This retrospective study was conducted from October 2013 to July 2015 at the Oculoplastic Clinic, Bundang CHA Medical Center, CHA University, Seongnam, Korea. A total of 122 eyes from 61 patients with upper eyelid epiblepharon were enrolled. Blepharoplasty with a BDTS technique was performed on all eyes, followed by evaluation of clinical outcomes and complications. After surgery, success was defined as the persistence of a double eyelid and the upper eyelid eyelashes not touching the cornea under slit lamp examination. RESULTS: The 61 patients were composed of 29 females and 32 males. The average age was 9.0 +/- 7.7 years, and the average follow-up period was 7.3 +/- 5.2 months. After surgery, the margin reflex distance increased from 2.0 +/- 1.0 to 3.2 +/- 0.9 mm (P < 0.05). The success rate was 98.1%. Epiblepharon recurred in 1 patient (1.9%) and was treated after 2 months. Knot exposure was a postoperative complication in 2 patients (3.8%). The knots were buried in the deep layer under local anesthesia. Overall, all cases showed good results without complications. CONCLUSIONS: Blepharoplasty with a BDTS technique is relatively simple and effective for correction of epiblepharon with a low rate of complications. This technique can be applied to double eyelid surgery based on the excellent cosmetic outcomes. PMID- 27200248 TI - Vascularized Nerve Bypass Graft: A Case Report of an Additional Treatment for Poor Sensory Recovery. AB - End-to-side neurorrhaphy has proven effective in basic research and in clinical application. One of the methods of end-to-side neurorrhaphy, nerve bypass technique, has been reported and axon regeneration has been proven. In clinical application, the utility of the nerve bypass technique has been revealed in some cases; however, these bypasses were performed using nonvascularized nerves. We initially used the vascularized nerve bypass graft technique with the sural nerve as a secondary clinical procedure after median nerve injury in a 61-year-old patient and achieved motor and sensory nerve regeneration, as supported by a nerve conduction study and clinical sensory test. This technique has the potential to become one of the choices for salvage procedure of severe nerve injury. PMID- 27200249 TI - Entrapment of the Flexor Digitorum Profundus in the Callus after a Closed Distal Radial Fracture. AB - A 17-year-old boy sustained a closed distal radius fracture; a closed reduction and external fixation was performed. After failed rehabilitation for digital flexion restriction, a surgical exploration was decided, revealing entrapment of flexor digitorum profundus in the bony callus; tendons were freed, obtaining a full range of motion. PMID- 27200250 TI - Novel Technique for Sampling of Breast Implant-associated Seroma in Anaplastic Large Cell Lymphoma. AB - We describe a novel technique for the sampling of breast implant-associated seroma. Using a blunt-tip lipofilling cannula, we have the freedom of movement to sample all fluid collections and prevent the misfortunes of damaging the implant. Also, we have demonstrated the inability of the Coleman style I lipofilling cannula to perforate a silicone breast implant. This practical and reliable technique will prove to be useful in managing the breast implant-associated seroma, especially with the rising incidence of the anaplastic large cell lymphoma, where the sampling of seroma is mandatory. PMID- 27200251 TI - Three-dimensional Printing of Models of Cleft Lip and Palate. AB - Supplemental Digital Content is available in the text. PMID- 27200252 TI - FTSG on the Face: Do We Really Need Tie-over Dressings or Quilting Sutures? PMID- 27200253 TI - Our Experience with 131 Cases of Simultaneous Breast Implant Exhange with Fat (SIEF). AB - BACKGROUND: Breast augmentation with fat injection is a growing trend in Japan. Many Japanese patients experiencing breast implant complications are requesting to have their breast implants removed and simultaneously exchanged with autologous fat injection. The keys of our simultaneous implant exchange with fat (SIEF) process are to embrace the "Coleman technique" and to carefully detach implant capsules when removing breast implants. Furthermore, we carefully inject fat to avoid necrosis. METHODS: Between January 2010 and January 2015, we investigated consecutively 131 Japanese patients whom we could follow up for over 6 months postsurgery. We ascertained the usefulness of SIEF by assessing changes in breast size, complications, and a satisfaction survey. RESULTS: There were no serious complications. We had experienced mild complications in 9.2% of patients (12/131). Partial fat necrosis with inflammation occurred in 2.3% of patients (3/131), seroma in the capsule in 3.1% (4/131), complaints of nodules (cysts, lumps) in 3.1% (4/131), and 1 hematoma patient (0.8%). At 6 months after surgery (n = 131), breast cup size (by Japanese Industrial Standards) had decreased by less than 1 cup size, despite SIEF. At 6 months, we performed a postsurgery satisfaction survey, and only 4% of the patients (5/131) were not satisfied with their surgery results. CONCLUSIONS: SIEF is a very safe and effective procedure. Breast implants removed with a low invasive traumatic approach and centrifuged fat injected with the "Coleman technique" are important principles in our practice. Furthermore, avoiding fat necrosis is one of the most important considerations, and our SIEF approach allows us to better control this potential complication during the surgical process. PMID- 27200254 TI - Masseter Atrophication after Masseteric Nerve Transfer. Is It Negligible? AB - Supplemental Digital Content is available in the text. PMID- 27200255 TI - Reconstruction of Extensive Volar Finger Defects with Double Cross-Finger Flaps. AB - Cross-finger flaps still represent a viable option to reconstruct small- to medium-sized full-thickness finger defects but they are not commonly used if larger areas have to be covered. We present 2 cases showing a simple and pragmatic approach with homodigital double cross-finger flaps to reconstruct extensive volar finger soft-tissue defects. We observed very low donor-site morbidity and excellent functional and aesthetic outcomes. Furthermore, there is no need for microsurgical techniques or equipment when using this method. Although this case report only addresses volar defects, one might also think of applying this concept to dorsal defects using reversed double cross-finger flaps. PMID- 27200257 TI - Switch Flap for Upper Eyelid Reconstruction-How Soon Should the Flap Be Divided? AB - BACKGROUND: The results of a cohort of patients treated at one institution for upper eyelid reconstruction with the switch flap method after a defect due to excision of malignant tumor were reviewed. METHODS: A retrospective data file review of all patients who had undergone total upper eyelid reconstruction with the switch flap method was conducted at the Saga University Hospital between April 2000 and October 2014. The follow-up lasted for varying periods during which the preoperative and postoperative photographs were compared as well. RESULTS: A total of 10 patients with upper eyelid tumors, that is, 7 sebaceous carcinoma, 2 squamous cell carcinoma, and 1 basal cell carcinoma, underwent reconstructive surgery. With the switch flap technique, the defects resulting from tumor excision were completely covered in all cases. The mean of defect widths after tumor excision (A) was 18.8 mm (range, 15-25 mm), the mean of widths of switch flaps (B) was 13.3 mm (range, 8-22 mm), and the mean of B/A ratios was 0.69 (range, 0.5-0.88). When the switch flap was divided at 7 to 14 days, there was no flap loss, trichiasis, or corneal ulcer. CONCLUSION: Our protocol managed to make flaps with a B/A ratio of 0.5-0.7, and the flaps were divided at 7 to 14 days after surgery, the timing of which was much earlier than in the conventional method, lessening the possibility of complications. PMID- 27200256 TI - Patient Expectations of Bariatric and Body Contouring Surgery. AB - BACKGROUND: Patient expectations are important in bariatric and body contouring surgery because the goals include improvements in health-related quality of life, appearance, and body image. The aim of this study was to identify patient expectations along the weight loss journey and/or body contouring surgery. METHODS: This qualitative study took an interpretive description approach. Between September 2009 and February 2012, 49 patients were interviewed postbody contouring surgery. Data were analyzed using a line-by-line approach whereby expectations were identified and labeled as expected, unexpected, or neutral. Constant comparison was used to ensure coding was done consistently. Interviews continued until no new themes emerged. RESULTS: Participants described expectations according to appearance, health-related quality of life, and patient experience of care. Two areas stood out in terms of unmet expectations and included appearance and physical health, ie, recovery from body contouring surgery. Most participants, who underwent bariatric surgery, expected neither the extent of excess skin after weight loss nor how the excess skin would make them look and feel. For recovery, participants did not expect that it would be as long or as hard as it was in reality. CONCLUSIONS: A full understanding of outcomes and expectations for this patient population is needed to enhance patient education and improve shared medical decision making. Education materials should be informed by the collection of evidence-based patient-reported outcome information using measures such as the BODY-Q. A patient-reported outcome scale measuring patient expectations is needed for obese and bariatric patients. PMID- 27200258 TI - Aesthetic Total Reconstruction of Lower Eyelid Using Scapha Cartilage Graft on a Vascularized Propeller Flap. AB - BACKGROUND: The aim of this study was to review the results of a cohort of patients based on our experience with a new technique for total lower eyelid reconstruction after a large defect caused by malignant tumor and trauma. A scapha cartilage graft with small skin on a vascularized propeller flap was used for 16 cases requiring lower eyelid reconstruction. METHODS: Patients were identified from a database, and a retrospective case note review was conducted. The scapha cartilage graft was sutured to the margin of the defect of the palpebral conjunctiva and tarsus. The propeller flap, rotated by a perforator based lateral orbital flap or a subcutaneous-based nasolabial flap, was vascularized on the scapha cartilage graft as anterior lining of the lower eyelid. The follow-up, including results of slit-lamp examination, lasted for varying periods, but often it was for 12 months. RESULTS: The scapha cartilage graft with small skin on a vascularized propeller flap was viable in all cases. Slit-lamp examination detected no irritation or injury of the conjunctiva and cornea, and visual acuity was maintained in all cases. A deformity in the donor helix by this technique was also improved by getting a smaller skin harvested from the scapha. CONCLUSION: Use of the scapha cartilage graft with small skin on a vascularized propeller flap allows for a good fit to the orbit, short operative time under local anesthesia, good graft viability, and a good esthetic result with minimal donor site morbidity. PMID- 27200260 TI - Immune effects and antiacetylcholinesterase activity of Polygonum hydropiper L. AB - To determine the potential utility of Polygonum hydropiper (tade) as an anti dementia functional food, the present study assessed the acetylcholinesterase inhibitory and anti-inflammatory activities of tade crude extracts in human cells. Crude extracts of tade were obtained by homogenizing tade in distilled water and then heating the resulting crude extracts. The hot aqueous extracts were purified by centrifugation and freeze-dried. The inhibition of acetylcholinesterase (AChE) by tade was investigated quantitatively by Ellman's method. Furthermore, the in vitro effects on human leukocytes (phagocytic activity, phagosome-lysosome fusion, and superoxide anion release) of coating inactive Staphylococcus aureus cells with tade crude extracts were studied. The tade crude extracts inhibited AChE activity. Furthermore, they increased phagocytic activity and phagosome-lysosome fusion in human neutrophils and monocytes in a nominally dose-dependent manner. However, the tade crude extracts did not alter superoxide anion release (O2 (-)) from neutrophils. Our results confirmed that crude extracts of P. hydropiper exhibit antiacetylcholinesterase and immunostimulation activities in vitro. P. hydropiper thus is a candidate functional food for the prevention of dementia. PMID- 27200261 TI - Perioperative supplementation with bifidobacteria improves postoperative nutritional recovery, inflammatory response, and fecal microbiota in patients undergoing colorectal surgery: a prospective, randomized clinical trial. AB - The use of probiotics has been widely documented to benefit human health, but their clinical value in surgical patients remains unclear. The present study investigated the effect of perioperative oral administration of probiotic bifidobacteria to patients undergoing colorectal surgery. Sixty patients undergoing colorectal resection were randomized to two groups prior to resection. One group (n=31) received a probiotic supplement, Bifidobacterium longum BB536, preoperatively for 7-14 days and postoperatively for 14 days, while the other group (n=29) received no intervention as a control. The occurrences of postoperative infectious complications were recorded. Blood and fecal samples were collected before and after surgery. No significant difference was found in the incidence of postoperative infectious complications and duration of hospital stay between the two groups. In comparison to the control group, the probiotic group tended to have higher postoperative levels of erythrocytes, hemoglobin, lymphocytes, total protein, and albumin and lower levels of high sensitive C reactive proteins. Postoperatively, the proportions of fecal bacteria changed significantly; Actinobacteria increased in the probiotic group, Bacteroidetes and Proteobacteria increased in the control group, and Firmicutes decreased in both groups. Significant correlations were found between the proportions of fecal bacteria and blood parameters; Actinobacteria correlated negatively with blood inflammatory parameters, while Bacteroidetes and Proteobacteria correlated positively with blood inflammatory parameters. In the subgroup of patients who received preoperative chemoradiotherapy treatment, the duration of hospital stay was significantly shortened upon probiotic intervention. These results suggest that perioperative oral administration of bifidobacteria may contribute to a balanced intestinal microbiota and attenuated postoperative inflammatory responses, which may subsequently promote a healthy recovery after colorectal resection. PMID- 27200259 TI - Paneth cell alpha-defensins and enteric microbiota in health and disease. AB - Antimicrobial peptides are major effectors of innate immunity of multicellular organisms including humans and play a critical role in host defense, and their importance is widely recognized. The epithelium of the intestine is the largest surface area exposed to the outer environment, including pathogens, toxins and foods. The Paneth cell lineage of intestinal epithelial cells produces and secretes alpha-defensin antimicrobial peptides and functions in innate enteric immunity by removing pathogens and living symbiotically with commensal microbiota to contribute to intestinal homeostasis. Paneth cells secrete alpha-defensins, HD5 and HD6 in humans and cryptdins in mice, in response to bacterial, cholinergic and other stimuli. The alpha-defensins have selective activities against bacteria, eliciting potent microbicidal activities against pathogenic bacteria but minimal or no bactericidal activity against commensal bacteria. Therefore, alpha-defensins regulate the composition of the intestinal microbiota in vivo and play a role in homeostasis of the entire intestine. Recently, relationships between dysbiosis, or abnormal composition of the intestinal microbiota, and diseases such as inflammatory bowel disease and lifestyle diseases including obesity and atherosclerosis have been reported. Because alpha defensins regulate the composition of the intestinal microbiota, Paneth cells and their alpha-defensins may have a key role as one mechanism linking the microbiota and disease. PMID- 27200263 TI - A comparative study of bifidobacteria in human babies and adults. AB - The composition and diversity of the gut microbiota are known to be different between babies and adults. The aim of this project was to compare the level of bifidobacteria between babies and adults and to investigate the influence of lifestyle factors on the level of this bacterium in the gut. During this study, the levels of bifidobacteria in 10 human babies below 2 years of age were compared with that of 10 human adults above 40 years. The level of bifidobacteria proved to be significantly higher in babies in comparison with adults. This investigation concluded that a combination of several factors, such as age, diet, and BMI, has an important effect on the level of bifidobacteria in adults, while in babies, a combination of diet and age may influence the level of intestinal bifidobacteria. PMID- 27200262 TI - Oral administration of fermented milk supplemented with synbiotics can influence the physiological condition of Wistar rats in a dose-sensitive and sex-specific manner. AB - Fermented milk supplemented with two probiotic strains (Bifidobacterium lactis Bi 07 and Lactobacillus acidophilus NCFM) and a prebiotic (isomaltooligosaccharide) was orally administered to Wistar rats for 30 days using three dosages. A commercial yogurt was used as a placebo. After treatment, the total protein, hemoglobin, and albumin levels in serum were significantly increased in female rats compared with those in the control group (p<0.05), whereas no significant change occurred in the male rats. A significant decrease in serum glucose levels was observed in male rats administered a low dosage of the tested fermented milk (p<0.05). The serum triglyceride level was significantly decreased in both male and female rats (p<0.05). No significant differences were found between rats groups in body weight, food intake, food utilization rate, red blood cell counts, white blood cell counts, alanine aminotransferase, aspartate aminotransferase, urea nitrogen, creatinine, and total cholesterol. These results suggest that the fermented milk supplemented with synbiotics altered the nutritive status of the host animal and contributed to their health. However, such potent health promoting effects could be deeply associated with the dose and sex specific. Therefore, different physiological targets and population characteristics should be managed with different combinations of probiotics and prebiotics. PMID- 27200265 TI - Variability in baseline travel behaviour as a predictor of changes in commuting by active travel, car and public transport: a natural experimental study. AB - PURPOSE: To strengthen our understanding of the impact of baseline variability in mode choice on the likelihood of travel behaviour change. METHODS: Quasi experimental analyses in a cohort study of 450 commuters exposed to a new guided busway with a path for walking and cycling in Cambridge, UK. Exposure to the intervention was defined using the shortest network distance from each participant's home to the busway. Variability in commuter travel behaviour at baseline was defined using the Herfindahl-Hirschman Index, the number of different modes of transport used over a week, and the proportion of trips made by the main (combination of) mode(s). The outcomes were changes in the share of commute trips (i) involving any active travel, (ii) involving any public transport, and (iii) made entirely by car. Variability and change data were derived from a self-reported seven-day record collected before (2009) and after (2012) the intervention. Separate multinomial regression models were estimated to assess the influence of baseline variability on behaviour change, both independently and as an interaction effect with exposure to the intervention. RESULTS: All three measures of variability predicted changes in mode share in most models. The effect size for the intervention was slightly strengthened after including variability. Commuters with higher baseline variability were more likely to increase their active mode share (e.g. for HHI: relative risk ratio [RRR] for interaction 3.34, 95% CI 1.41, 7.89) and decrease their car mode share in response to the intervention (e.g. for HHI: RRR 7.50, 95% CI 2.52, 22.34). CONCLUSIONS: People reporting a higher level of variability in mode choice were more likely to change their travel behaviour following an intervention. Future research should consider such variability as a potential predictor and effect modifier of travel and physical activity behaviour change, and its significance for the design and targeting of interventions. PMID- 27200264 TI - The application of a mathematical model linking structural and functional connectomes in severe brain injury. AB - Following severe injuries that result in disorders of consciousness, recovery can occur over many months or years post-injury. While post-injury synaptogenesis, axonal sprouting and functional reorganization are known to occur, the network level processes underlying recovery are poorly understood. Here, we test a network-level functional rerouting hypothesis in recovery of patients with disorders of consciousness following severe brain injury. This hypothesis states that the brain recovers from injury by restoring normal functional connections via alternate structural pathways that circumvent impaired white matter connections. The so-called network diffusion model, which relates an individual's structural and functional connectomes by assuming that functional activation diffuses along structural pathways, is used here to capture this functional rerouting. We jointly examined functional and structural connectomes extracted from MRIs of 12 healthy and 16 brain-injured subjects. Connectome properties were quantified via graph theoretic measures and network diffusion model parameters. While a few graph metrics showed groupwise differences, they did not correlate with patients' level of consciousness as measured by the Coma Recovery Scale - Revised. There was, however, a strong and significant partial Pearson's correlation (accounting for age and years post-injury) between level of consciousness and network diffusion model propagation time (r = 0.76, p < 0.05, corrected), i.e. the time functional activation spends traversing the structural network. We concluded that functional rerouting via alternate (and less efficient) pathways leads to increases in network diffusion model propagation time. Simulations of injury and recovery in healthy connectomes confirmed these results. This work establishes the feasibility for using the network diffusion model to capture network-level mechanisms in recovery of consciousness after severe brain injury. PMID- 27200266 TI - Association of TLR and TREM-1 gene polymorphisms with atherosclerosis severity in a Russian population. AB - Local vascular immune response is primarily initiated via Toll-like receptors (TLRs) and triggering receptor expressed on myeloid cells-1 (TREM-1). We previously showed that certain TLR and TREM-1 gene polymorphisms are associated with coronary artery disease (CAD). Therefore, we hypothesized that these gene polymorphisms are associated with atherosclerosis severity. This study included 292 consecutive patients with CAD who were admitted to the Research Institute for Complex Issues of Cardiovascular Diseases (Kemerovo, Russian Federation) during 2011-2012. Sample genotyping was performed in 96-well format using the TaqMan SNP genotyping assay. We found that C/C genotype of the rs3804099 polymorphism within TLR2 gene and T/T genotype of the rs4711668 polymorphism within TREM-1 gene were significantly associated with severe coronary atherosclerosis while C allele of the rs5743551 polymorphism within TLR1 gene, A/G genotype of the rs4986790 polymorphism and C/T genotype of the rs4986791 polymorphism within TLR4 gene, and C allele of the rs3775073 polymorphism within TLR6 gene were significantly associated with severe noncoronary atherosclerosis. However, A/A genotype of the rs5743810 polymorphism within TLR6 gene was significantly associated with mild noncoronary atherosclerosis. We conclude that certain TLR and TREM-1 gene polymorphisms are significantly associated with atherosclerosis severity in a Russian population. PMID- 27200267 TI - Influence of cytokine and cytokine receptor gene polymorphisms on the degree of liver damage in patients with chronic hepatitis C. AB - Hepatic fibrosis may be the result of repetitive injury to hepatocytes caused by HCV infection and the immune response to it. Cytokines regulate the inflammatory response to injury and modulate hepatic fibrogenesis. Single nucleotide polymorphisms (SNPs) located in cytokine genes may influence the cytokine expression and secretion that may contribute to hepatic fibrogenesis in HCV infection. The aim of this study was to determine the genotype of 22 SNPs found in the genes of 13 cytokines/cytokine receptors to assess the influence of polymorphic variants on the stage of liver damage in Brazilian patients chronically infected with HCV genotype 1 only. 141 unrelated patients were grouped according to their stage of fibrosis: absence of fibrosis or patients in the initial stages of fibrosis (F0-F2, n = 84), patients with advanced stages of fibrosis or cirrhosis (F3-F4, n = 57), without cirrhosis (F0-F3, n = 103), and with cirrhosis (F4, n = 38). The comparison of frequencies in each sub-sample was performed by 2 * 2 contingency tables using the chi-square or Fisher's exact test. Stepwise logistic regression was also used to assess independent associations between cirrhosis or fibrosis with polymorphic variants. The TNFA 308G:A genotype conferred increased risk of fibrosis and cirrhosis. The TNFA 238G:G genotype was associated with protection from cirrhosis. The IL10-819C:T genotype conferred protection from fibrosis and the IL1B-511C:T genotype conferred increased risk of cirrhosis. Some of these genotypes showed results on the borderline of statistical significance in the bivariate analysis. We conclude that gene variants of cytokines/receptors may influence liver damage in patients chronically infected by HCV genotype 1. PMID- 27200268 TI - Inflammation-associated changes in lipid composition and the organization of the erythrocyte membrane. AB - BACKGROUND: Reduced erythrocyte survival and deformability may contribute to the so-called anemia of inflammation observed in septic patients. Erythrocyte structure and function are affected by both the membrane lipid composition and the organization. We therefore aimed to determine whether these parameters are affected during systemic inflammation. METHODS: A sensitive matrix-assisted laser desorption and ionization time-of-flight mass spectrometric method was used to investigate the effect of plasma components of 10 patients with septic shock and of 10 healthy volunteers subjected to experimental endotoxemia on erythrocyte membrane lipid composition. RESULTS: Incubation of erythrocytes from healthy control donors with plasma from patients with septic shock resulted in membrane phosphatidylcholine hydrolysis into lysophosphatidylcholine (LPC). Plasma from volunteers undergoing experimental human endotoxemia did not induce LPC formation. The secretory phospholipase A2 IIA concentration was enhanced up to 200-fold in plasma of septic patients and plasma from endotoxin-treated subjects, but did not correlate with the ability of these plasmas to generate LPC. Erythrocyte phosphatidylserine exposure increased up to two-fold during experimental endotoxemia. CONCLUSIONS: Erythrocyte membrane lipid remodeling as reflected by LPC formation and/or PS exposure occurs during systemic inflammation in a secretory phospholipase A2 IIA-independent manner. GENERAL SIGNIFICANCE: Sepsis-associated inflammation induces a lipid remodeling of the erythrocyte membrane that is likely to affect erythrocyte function and survival, and that is not fully mimicked by experimental endotoxemia. PMID- 27200269 TI - Comparison of rapid solvent extraction systems for the GC-MS/MS characterization of polycyclic aromatic hydrocarbons in aged, contaminated soil. AB - Polycyclic aromatic hydrocarbons (PAHs) are a major class of organic hydrocarbons with high molecular weight that originate from both natural and anthropogenic sources. Sixteen PAHs are included in the U.S Environmental Protection agency list of priority pollutants due to their mutagenic, carcinogenic, toxic and teratogenic properties. In this study, the development and optimization of a simplified and rapid solvent extraction for the characterisation of 16 USEPA priority poly aromatic hydrocarbons (PAHs) in aged contaminated soils was established with subsequent analysis by GC-MS/MS. *Five different extraction solvent systems: dichloromethane: acetone, chloroform: methanol, dichloromethane, acetone: hexane and hexane were assessed in terms of their ability to extract PAHs from aged PAH-contaminated soils.*Highest PAH concentrations were extracted using acetone: hexane and chloroform: methanol. Given the greater toxicity associated with chloroform: methanol, acetone: hexane appears the best choice of solvent extraction system.*This protocol enables efficient extraction of PAHs from aged weathered soils. PMID- 27200271 TI - First molecular evidence of Toxoplasma gondii in opossums (Didelphis virginiana) from Yucatan, Mexico. AB - Toxoplasma gondii is an obligate intracellular parasite recognized as a causal agent of toxoplasmosis; zoonotic disease endemic in many countries worldwide, including Mexico. Different species of animals participate in the wild cycle infection, including opossums of the species Didelphis virginiana. Thirteen D. virginiana were captured in Yucatan, Mexico. Detection of T. gondii was achieved by Polymerase Chain Reaction, which determined an infection of 76.9% (10/13) in brains. Positive amplicons were sequenced for analysis, this produced results similar to T. gondii with identity and coverage values of 98% and 96-100%, respectively. This study presents the first molecular evidence of the circulation of T. gondii in D. virginiana from Mexico. PMID- 27200272 TI - Anaesthetic management of a unilateral adrenalectomy of an adrenocortical tumour in a dog. AB - Adrenalectomies in dogs are being more commonly performed, however anaesthetic management of such cases can be challenging due to the multiple aetiologies of adrenal tumours and the physiological role of adrenal glands. This case report describes the anaesthetic management of a dog with clinical signs of hyperadrenocorticism that underwent unilateral adrenalectomy via laparotomy and discusses anaesthetic preparedness, protocol selection and management of complications for dogs undergoing adrenalectomy. PMID- 27200270 TI - Integrative veterinary medical education and consensus guidelines for an integrative veterinary medicine curriculum within veterinary colleges. AB - Integrative veterinary medicine (IVM) describes the combination of complementary and alternative therapies with conventional care and is guided by the best available evidence. Veterinarians frequently encounter questions about complementary and alternative veterinary medicine (CAVM) in practice, and the general public has demonstrated increased interest in these areas for both human and animal health. Consequently, veterinary students should receive adequate exposure to the principles, theories, and current knowledge supporting or refuting such techniques. A proposed curriculum guideline would broadly introduce students to the objective evaluation of new veterinary treatments while increasing their preparation for responding to questions about IVM in clinical practice. Such a course should be evidence-based, unbiased, and unaffiliated with any particular CAVM advocacy or training group. All IVM courses require routine updating as new information becomes available. Controversies regarding IVM and CAVM must be addressed within the course and throughout the entire curriculum. Instructional honesty regarding the uncertainties in this emerging field is critical. Increased training of future veterinary professionals in IVM may produce an openness to new ideas that characterizes the scientific method and a willingness to pursue and incorporate evidence-based medicine in clinical practice with all therapies, including those presently regarded as integrative, complementary, or alternative. PMID- 27200273 TI - A case of advanced second-degree atrioventricular block in a ferret secondary to lymphoma. AB - A female ferret was referred as an emergency for severe respiratory distress symptoms. At presentation, the patient was listlessness, dyspnoeic, and hyper responsive. The clinical examination evidenced dyspnea with cyanosis, altered cardiac rhythm, and hepatomegaly. Electrocardiography showed an advanced second degree atrioventricular (AV) block. The liver aspirate was diagnostic for lymphoma. The patient did not respond to supportive therapy and rapidly died. Post-mortem exams confirmed the presence of lymphoma with hepatic involvement. Moreover, a pericardial lymphocytic infiltration and a widespread myocardial nodular localization of lymphoma were evidenced as well. This condition was probably the cause of the cardiac arrhythmia. To the best of our knowledge, ours is the first report of cardiac lymphoma causing heart block in ferrets. PMID- 27200275 TI - Marginal microleakage of cervical composite resin restorations bonded using etch and-rinse and self-etch adhesives: two dimensional vs. three dimensional methods. AB - OBJECTIVES: This study was evaluated the marginal microleakage of two different adhesive systems before and after aging with two different dye penetration techniques. MATERIALS AND METHODS: Class V cavities were prepared on the buccal and lingual surfaces of 48 human molars. Clearfil SE Bond and Single Bond (self etching and etch-and-rinse systems, respectively) were applied, each to half of the prepared cavities, which were restored with composite resin. Half of the specimens in each group underwent 10,000 cycles of thermocycling. Microleakage was evaluated using two dimensional (2D) and three dimensional (3D) dye penetration techniques separately for each half of each specimen. Data were analyzed with SPSS 11.5 (SPSS Inc.), using the Kruskal-Wallis and Mann-Whitney U tests (alpha = 0.05). RESULTS: The difference between the 2D and 3D microleakage evaluation techniques was significant at the occlusal margins of Single bond groups (p = 0.002). The differences between 2D and 3D microleakage evaluation techniques were significant at both the occlusal and cervical margins of Clearfil SE Bond groups (p = 0.017 and p = 0.002, respectively). The difference between the 2D and 3D techniques was significant at the occlusal margins of non-aged groups (p = 0.003). The difference between these two techniques was significant at the occlusal margins of the aged groups (p = 0.001). The Mann-Whitney test showed significant differences between the two techniques only at the occlusal margins in all specimens. CONCLUSIONS: Under the limitations of the present study, it can be concluded that the 3D technique has the capacity to detect occlusal microleakage more precisely than the 2D technique. PMID- 27200276 TI - Antifungal effects of synthetic human beta-defensin 3-C15 peptide. AB - OBJECTIVES: The purpose of this ex vivo study was to compare the antifungal activity of a synthetic peptide consisting of 15 amino acids at the C-terminus of human beta-defensin 3 (HBD3-C15) with calcium hydroxide (CH) and Nystatin (Nys) against Candida albicans (C. albicans) biofilm. MATERIALS AND METHODS: C. albicans were grown on cover glass bottom dishes or human dentin disks for 48 hr, and then treated with HBD3-C15 (0, 12.5, 25, 50, 100, 150, 200, and 300 ug/mL), CH (100 ug/mL), and Nys (20 ug/mL) for 7 days at 37C. On cover glass, live and dead cells in the biomass were measured by the FilmTracer Biofilm viability assay, and observed by confocal laser scanning microscopy (CLSM). On dentin, normal, diminished and ruptured cells were observed by field-emission scanning electron microscopy (FE-SEM). The results were subjected to a two-tailed t-test, a one way analysis variance and a post hoc test at a significance level of p = 0.05. RESULTS: C. albicans survival on dentin was inhibited by HBD3-C15 in a dose dependent manner. There were fewer aggregations of C. albicans in the groups of Nys and HBD3-C15 (>= 100 ug/mL). CLSM showed C. albicans survival was reduced by HBD3-C15 in a dose dependent manner. Nys and HBD3-C15 (>= 100 ug/mL) showed significant fungicidal activity compared to CH group (p < 0.05). CONCLUSIONS: Synthetic HBD3-C15 peptide (>= 100 ug/mL) and Nys exhibited significantly higher antifungal activity than CH against C. albicans by inhibiting cell survival and biofilm. PMID- 27200277 TI - Biocompatibility of two experimental scaffolds for regenerative endodontics. AB - OBJECTIVES: The biocompatibility of two experimental scaffolds for potential use in revascularization or pulp regeneration was evaluated. MATERIALS AND METHODS: One resilient lyophilized collagen scaffold (COLL), releasing metronidazole and clindamycin, was compared to an experimental injectable poly(lactic-co-glycolic) acid scaffold (PLGA), releasing clindamycin. Human dental pulp stem cells (hDPSCs) were seeded at densities of 1.0 * 10(4), 2.5 * 10(4), and 5.0 * 10(4). The cells were investigated by light microscopy (cell morphology), MTT assay (cell proliferation) and a cytokine (IL-8) ELISA test (biocompatibility). RESULTS: Under microscope, the morphology of cells coincubated for 7 days with the scaffolds appeared healthy with COLL. Cells in contact with PLGA showed signs of degeneration and apoptosis. MTT assay showed that at 5.0 * 10(4) hDPSCs, COLL demonstrated significantly higher cell proliferation rates than cells in media only (control, p < 0.01) or cells co-incubated with PLGA (p < 0.01). In ELISA test, no significant differences were observed between cells with media only and COLL at 1, 3, and 6 days. Cells incubated with PLGA expressed significantly higher IL-8 than the control at all time points (p < 0.01) and compared to COLL after 1 and 3 days (p < 0.01). CONCLUSIONS: The COLL showed superior biocompatibility and thus may be suitable for endodontic regeneration purposes. PMID- 27200278 TI - Orthodontic bracket bonding to glazed full-contour zirconia. AB - OBJECTIVES: This study evaluated the effects of different surface conditioning methods on the bond strength of orthodontic brackets to glazed full-zirconia surfaces. MATERIALS AND METHODS: Glazed zirconia (except for the control, Zirkonzahn Prettau) disc surfaces were pre-treated: PO (control), polishing; BR, bur roughening; PP, cleaning with a prophy cup and pumice; HF, hydrofluoric acid etching; AA, air abrasion with aluminum oxide; CJ, CoJet-Sand. The surfaces were examined using profilometry, scanning electron microscopy, and electron dispersive spectroscopy. A zirconia primer (Z-Prime Plus, Z) or a silane primer (Monobond-S, S) was then applied to the surfaces, yielding 7 groups (PO-Z, BR-Z, PP-S, HF-S, AA-S, AA-Z, and CJ-S). Metal bracket-bonded specimens were stored in water for 24 hr at 37C, and thermocycled for 1,000 cycles. Their bond strengths were measured using the wire loop method (n = 10). RESULTS: Except for BR, the surface pre-treatments failed to expose the zirconia substructure. A significant difference in bond strengths was found between AA-Z (4.60 +/- 1.08 MPa) and all other groups (13.38 +/- 2.57 - 15.78 +/- 2.39 MPa, p < 0.05). For AA-Z, most of the adhesive remained on the bracket. CONCLUSIONS: For bracket bonding to glazed zirconia, a simple application of silane to the cleaned surface is recommended. A zirconia primer should be used only when the zirconia substructure is definitely exposed. PMID- 27200274 TI - Tularemia vaccine development: paralysis or progress? AB - Francisella tularensis (Ft) is a gram-negative intercellular pathogen and category A biothreat agent. However, despite 15 years of strong government investment and intense research focused on the development of a US Food and Drug Administration-approved vaccine against Ft, the primary goal remains elusive. This article reviews research efforts focused on developing an Ft vaccine, as well as a number of important factors, some only recently recognized as such, which can significantly impact the development and evaluation of Ft vaccine efficacy. Finally, an assessment is provided as to whether a US Food and Drug Administration-approved Ft vaccine is likely to be forthcoming and the potential means by which this might be achieved. PMID- 27200280 TI - The effect of different fluoride application methods on the remineralization of initial carious lesions. AB - OBJECTIVES: The purpose of this study was to assess the effect of single and combined applications of fluoride on the amount of fluoride release, and the remineralization and physical properties of enamel. MATERIALS AND METHODS: Each of four fluoride varnish and gel products (Fluor Protector, FP, Ivoclar Vivadent; Tooth Mousse Plus, TM, GC; 60 Second Gel, A, Germiphene; CavityShield, CS, 3M ESPE) and two fluoride solutions (2% sodium fluoride, N; 8% tin(ii) fluoride, S) were applied on bovine teeth using single and combined methods (10 per group), and then the amount of fluoride release was measured for 4 wk. The electron probe microanalysis and the Vickers microhardness measurements were conducted to assess the effect of fluoride application on the surface properties of bovine teeth. RESULTS: The amount of fluoride release was higher in combined applications than in single application (p < 0.05). Microhardness values were higher after combined applications of N with FP, TM, and CS than single application of them, and these values were also higher after combined applications of S than single application of A (p < 0.05). Ca and P values were higher in combined applications of N with TM and CS than single application of them (p < 0.05). They were also increased after combined applications of the S with A than after single application (p < 0.05). CONCLUSIONS: Combined applications of fluoride could be used as a basis to design more effective methods of fluoride application to provide enhanced remineralization. PMID- 27200279 TI - Push-out bond strength and dentinal tubule penetration of different root canal sealers used with coated core materials. AB - OBJECTIVES: The aim of this study was to compare the push-out bond strength and dentinal tubule penetration of root canal sealers used with coated core materials and conventional gutta-percha. MATERIALS AND METHODS: A total of 72 single-rooted human mandibular incisors were instrumented with NiTi rotary files with irrigation of 2.5% NaOCl. The smear layer was removed with 17% ethylenediaminetetraacetic acid (EDTA). Specimens were assigned into four groups according to the obturation system: Group 1, EndoRez (Ultradent Product Inc.); Group 2, Activ GP (Brasseler); Group 3, SmartSeal (DFRP Ltd. Villa Farm); Group 4, AH 26 (Dentsply de Trey)/gutta-percha (GP). For push-out bond strength measurement, two horizontal slices were obtained from each specimen (n = 20). To compare dentinal tubule penetration, remaining 32 roots assigned to 4 groups as above were obturated with 0.1% Rhodamine B labeled sealers. One horizontal slice was obtained from the middle third of each specimen (n = 8) and scanned under confocal laser scanning electron microscope. Tubule penetration area, depth, and percentage were measured. Kruskall-Wallis test was used for statistical analysis. RESULTS: EndoRez showed significantly lower push-out bond strength than the others (p < 0.05). No significant difference was found amongst the groups in terms of percentage of sealer penetration. SmartSeal showed the least penetration than the others (p < 0.05). CONCLUSIONS: The bond strength and sealer penetration of resin-and glass ionomer-based sealers used with coated core was not superior to resin-based sealer used with conventional GP. Dentinal tubule penetration has limited effect on bond strength. The use of conventional GP with sealer seems to be sufficient in terms of push-out bond strength. PMID- 27200281 TI - The effect of red and white wine on color changes of nanofilled and nanohybrid resin composites. AB - OBJECTIVES: This study investigated the effect of red and white wine on color changes of nanofilled and nanohybrid resin composite. MATERIALS AND METHODS: Sixty specimens of each resin composite were prepared. Baseline data color values were recorded using a spectrophotometer. Three groups of discs (n = 20) were then alternately immersed in red, white wine, and deionized water (as a control) for twenty five minutes and artificial saliva for five minutes for four cycles. Specimens were then stored in artificial saliva for twenty two hours. This process was repeated for five days following immersion in artificial saliva for two days. Subsequently, the process was repeated again. Data were analyzed by two way repeated ANOVA, one-way ANOVA, and Tukey's HSD. RESULTS: Red wine caused significantly higher color change (DeltaE(*) > 3.3) than did white wine and deionized water (p < 0.05). Nanohybrid resin composites had significantly more color changes than nanofilled resin composite (p < 0.05). CONCLUSIONS: The effect of red and white wine on the color changes of resin composite restorative materials depended upon the physical and chemical composition of the restorative materials and the types of wine. PMID- 27200282 TI - Progression of periapical cystic lesion after incomplete endodontic treatment. AB - We report a case of large radicular cyst progression related to endodontic origin to emphasize proper intervention and follow-up for endodontic pathosis. A 25 yr old man presented with an endodontically treated molar with radiolucency. He denied any intervention because of a lack of discomfort. Five years later, the patient returned. The previous periapical lesion had drastically enlarged and involved two adjacent teeth. Cystic lesion removal and apicoectomy were performed on the tooth. Histopathological analysis revealed that the lesion was an inflammatory radicular cyst. The patient did not report any discomfort except for moderate swelling 3 days after the surgical procedure. Although the patient had been asymptomatic, close follow-ups are critical to determine if any periapical lesions persist after root canal treatment. PMID- 27200283 TI - Fibre reinforcement in a structurally compromised endodontically treated molar: a case report. AB - The reconstruction of structurally compromised posterior teeth is a rather challenging procedure. The tendency of endodontically treated teeth (ETT) to fracture is considerably higher than vital teeth. Although posts and core build ups followed by conventional crowns have been generally employed for the purpose of reconstruction, this procedure entails sacrificing a considerable amount of residual sound enamel and dentin. This has drawn the attention of researchers to fibre reinforcement. Fibre-reinforced composite (FRC), designed to replace dentin, enables the biomimetic restoration of teeth. Besides improving the strength of the restoration, the incorporation of glass fibres into composite resins leads to favorable fracture patterns because the fibre layer acts as a stress breaker and stops crack propagation. The following case report presents a technique for reinforcing a badly broken-down ETT with biomimetic materials and FRC. The proper utilization of FRC in structurally compromised teeth can be considered to be an economical and practical measure that may obviate the use of extensive prosthetic treatment. PMID- 27200284 TI - Nonsurgical endodontic retreatment of fused teeth with transposition: a case report. AB - Tooth transposition is a disorder in which a permanent tooth develops and erupts in the normal position of another permanent tooth. Fusion and gemination are developmental disturbances presenting as the union of teeth. This article reports the nonsurgical retreatment of a very rare case of fused teeth with transposition. A patient was referred for endodontic treatment of her maxillary left first molar in the position of the first premolar, which was adjacent to it on the distobuccal side. Orthopantomography and periapical radiography showed two crowns sharing the same root, with a root canal treatment and an associated periapical lesion. Tooth fusion with transposition of a maxillary molar and a premolar was diagnosed. Nonsurgical endodontic retreatment was performed. At four yr follow-up, the tooth was asymptomatic and the radiolucency around the apical region had decreased, showing the success of our intervention. The diagnosis and treatment of fused teeth require special attention. The canal system should be carefully explored to obtain a full understanding of the anatomy, allowing it to be fully cleaned and obturated. Thermoplastic techniques were useful in obtaining hermetic obturation. A correct anatomical evaluation improves the set of treatment options under consideration, leading to a higher likelihood of esthetically and functionally successful treatment. PMID- 27200285 TI - Statistical notes for clinical researchers: Sample size calculation 2. Comparison of two independent proportions. PMID- 27200286 TI - Phosphoric acid etching for multi-mode universal adhesive. PMID- 27200287 TI - Durable Response of Spinal Chordoma to Combined Inhibition of IGF-1R and EGFR. AB - Chordomas are rare primary malignant bone tumors arising from embryonal notochord remnants of the axial skeleton. Chordomas commonly recur following surgery and radiotherapy, and there is no effective systemic therapy. Previous studies implicated receptor tyrosine kinases, including epidermal growth factor receptor (EGFR) and type 1 insulin-like growth factor receptor (IGF-1R), in chordoma biology. We report an adult female patient who presented in 2003 with spinal chordoma, treated with surgery and radiotherapy. She underwent further surgery for recurrent chordoma in 2008, with subsequent progression in pelvic deposits. In June 2009, she was recruited onto the Phase I OSI-906-103 trial of EGFR inhibitor erlotinib with linsitinib, a novel inhibitor of IGF-1R/insulin receptor (INSR). Treatment with 100 mg QD erlotinib and 50 mg QD linsitinib was well tolerated, and after 18 months a partial response was achieved by RECIST criteria. From 43 months, a protocol modification allowed intra-patient linsitinib dose escalation to 50 mg BID. The patient remained stable on trial treatment for a total of 5 years, discontinuing treatment in August 2014. She subsequently experienced further disease progression for which she underwent pelvic surgery in April 2015. Analysis of DNA extracted from 2008 (pre-trial) tissue showed that the tumor harbored wild-type EGFR, and a PIK3CA mutation was detected in plasma, but not tumor DNA. The 2015 (post-trial) tumor harbored a mutation of uncertain significance in ATM, with no detectable mutations in other components of a 50 gene panel, including EGFR, PIK3CA, and TP53. By immunohistochemistry, the tumor was positive for brachyury, the molecular hallmark of chordoma, and showed weak-moderate membrane and cytoplasmic EGFR. IGF 1R was detected in the plasma membrane and cytoplasm and was expressed more strongly in recurrent tumor than the primary. We also noted heterogeneous nuclear IGF-1R, which has been linked with sensitivity to IGF-1R inhibition. Similar variation in IGF-1R expression and subcellular localization was noted in 15 further cases of chordoma. In summary, this exceptionally durable response suggests that there may be merit in evaluating combined IGF-1R/INSR and EGFR inhibition in patients with chordomas that recur following failure of local treatment. PMID- 27200288 TI - Targeting mTOR in Pancreatic Ductal Adenocarcinoma. AB - Treatment options for advanced pancreatic ductal adenocarcinoma (PDAC) are limited; however, new therapies targeting specific tumor-related molecular characteristics may help certain patient cohorts. Emerging preclinical data have shown that inhibition of mammalian target of rapamycin (mTOR) in specific KRAS dependent PDAC subtypes leads to inhibition of tumorigenesis in vitro and in vivo. Early phase II studies of mono-mTOR inhibition have not shown promise. However, studies have shown that combined inhibition of multiple steps along the mTOR signaling pathway may lead to sustained responses by targeting mechanisms of tumor resistance. Coordinated inhibition of mTOR along with specific KRAS dependent mutations in molecularly defined PDAC subpopulations may offer a viable alternative for treatment in the future. PMID- 27200289 TI - Estrogen Receptor-Targeted Contrast Agents for Molecular Magnetic Resonance Imaging of Breast Cancer Hormonal Status. AB - The estrogen receptor (ER) alpha is overexpressed in most breast cancers, and its level serves as a major prognostic factor. It is important to develop quantitative molecular imaging methods that specifically detect ER in vivo and assess its function throughout the entire primary breast cancer and in metastatic breast cancer lesions. This study presents the biochemical and molecular features, as well as the magnetic resonance imaging (MRI) effects of two novel ER targeted contrast agents (CAs), based on pyridine-tetra-acetate-Gd(III) chelate conjugated to 17beta-estradiol (EPTA-Gd) or to tamoxifen (TPTA-Gd). The experiments were conducted in solution, in human breast cancer cells, and in severe combined immunodeficient mice implanted with transfected ER-positive and ER-negative MDA-MB-231 human breast cancer xenografts. Binding studies with ER in solution and in human breast cancer cells indicated affinities in the micromolar range of both CAs. Biochemical and molecular studies in breast cancer cell cultures showed that both CAs exhibit estrogen-like agonistic activity, enhancing cell proliferation, as well as upregulating cMyc oncogene and downregulating ER expression levels. The MRI longitudinal relaxivity was significantly augmented by EPTA-Gd in ER-positive cells as compared to ER-negative cells. Dynamic contrast enhanced studies with EPTA-Gd in vivo indicated specific augmentation of the MRI water signal in the ER-positive versus ER-negative xenografts, confirming EPTA-Gd specific interaction with ER. In contrast, TPTA-Gd did not show increased enhancement in ER-positive tumors and did not appear to interact in vivo with the tumors' ER. However, TPTA-Gd was found to interact strongly with muscle tissue, enhancing muscle signal intensity in a mechanism independent of the presence of ER. The specificity of EPTA-Gd interaction with ER in vivo was further verified by acute and chronic competition with tamoxifen. The chronic tamoxifen treatment also revealed that this drug increases the microvascular permeability of breast cancer xenograft in an ER-independent manner. In conclusion, EPTA-Gd has been shown to serve as an efficient molecular imaging probe for specific assessment of breast cancer ER in vivo. PMID- 27200290 TI - Disparities in Receipt of Radiotherapy and Survival by Age, Sex, and Ethnicity among Patient with Stage I Follicular Lymphoma. AB - BACKGROUND: Radiotherapy (RT) is a first-line treatment option for stage I follicular lymphoma (FL). We studied disparities in receipt of RT and survival among patients with stage I FL. METHODS: Adult patients (age >=18 years) with stage I FL, as the first primary cancer, diagnosed between 1992 and 2007 were identified using Surveillance, Epidemiology, and End Results (SEER) 18 database. Study population was divided into various subgroups based on age, sex, race, and marital status. Factors associated with receipt of RT and survival, among patients receiving RT, was evaluated using regression analysis and Cox PH modeling, respectively. SEER*Stat was used to compute 1- and 5-year RS for various subgroups and compared using Z score. RESULTS: Of the total 7315 patients (median age: 64 years), 2671 (36.5%) received RT. African-Americans, older age group, and single and separated/divorced/widow marital status predicted omission of RT. The 1- and 5-year RS were significantly better in patients receiving RT. In multivariate analysis, male sex, age <60 years, Caucasian race, and married marital status were found to be independent predictor of better RS among patients receiving RT (P < 0.0001). CONCLUSION: This study showed that 36.5% patients with stage I FL received RT. Survival rates were significantly better for patients who received RT. PMID- 27200292 TI - Clinical Trial Accrual: Obstacles and Opportunities. PMID- 27200291 TI - Fertility Preservation: A Key Survivorship Issue for Young Women with Cancer. AB - Fertility preservation in the young cancer survivor is recognized as a key survivorship issue by the American Society of Clinical Oncology and the American Society of Reproductive Medicine. Thus, health-care providers should inform women about the effects of cancer therapy on fertility and should discuss the different fertility preservation options available. It is also recommended to refer women expeditiously to a fertility specialist in order to improve counseling. Women's age, diagnosis, presence of male partner, time available, and preferences regarding use of donor sperm influence the selection of the appropriate fertility preservation option. Embryo and oocyte cryopreservation are the standard techniques used while ovarian tissue cryopreservation is new, yet promising. Despite the importance of fertility preservation for cancer survivors' quality of life, there are still communication and financial barriers faced by women who wish to pursue fertility preservation. PMID- 27200294 TI - Confronting the Care Delivery Challenges Arising from Precision Medicine. AB - Understanding the biology of cancer at the cellular and molecular levels, and the application of such knowledge to the patient, has opened new opportunities and uncovered new obstacles to quality cancer care delivery. Benefits include our ability to now understand that many, if not most, cancers are not one-size-fits all. Cancers are a variety of diseases for which intervention may be very different. This approach is beginning to bear fruit in gynecologic cancers where we are investigating therapeutic optimization at a more focused level, that while not yet precision care, is perhaps much improved. Obstacles to quality care for patients come from many directions. These include incomplete understanding of the role of the mutant proteins in the cancers, the narrow spectrum of agents, broader mutational profiles in solid tumors, and sometimes overzealous application of the findings of genetic testing. This has been further compromised by the unbridled use of social media by all stakeholders in cancer care often without scientific qualification, where anecdote sometimes masquerades as a fact. The only current remedy is to wave the flag of caution, encourage all patients who undergo genetic testing, either germline or somatic, to do so with the oversight of genetic counselors and physician scientists knowledgeable in the pathways involved. This aspiration is accomplished with well-designed clinical trials that inform next steps in this complex and ever evolving process. PMID- 27200293 TI - Metabolic Study of Breast MCF-7 Tumor Spheroids after Gamma Irradiation by (1)H NMR Spectroscopy and Microimaging. AB - Multicellular tumor spheroids are an important model system to investigate the response of tumor cells to radio- and chemotherapy. They share more properties with the original tumor than cells cultured as 2D monolayers do, which helps distinguish the intrinsic properties of monolayer cells from those induced during cell aggregation in 3D spheroids. The paper investigates some metabolic aspects of small tumor spheroids of breast cancer and their originating MCF-7 cells, grown as monolayer, by means of high-resolution (HR) (1)H NMR spectroscopy and MR microimaging before and after gamma irradiation. The spectra of spheroids were characterized by higher intensity of mobile lipids, mostly neutral lipids, and glutamine (Gln) signals with respect to their monolayer cells counterpart, mainly owing to the lower oxygen supply in spheroids. Morphological changes of small spheroids after gamma-ray irradiation, such as loss of their regular shape, were observed by MR microimaging. Lipid signal intensity increased after irradiation, as evidenced in both MR localized spectra of the single spheroid and in HR NMR spectra of spheroid suspensions. Furthermore, the intense Gln signal from spectra of irradiated spheroids remained unchanged, while the low Gln signal observed in monolayer cells increased after irradiation. Similar results were observed in cells grown in hypoxic conditions. The different behavior of Gln in 2D monolayers and in 3D spheroids supports the hypothesis that a lower oxygen supply induces both an upregulation of Gln synthetase and a downregulation of glutaminases with the consequent increase in Gln content, as already observed under hypoxic conditions. The data herein indicate that (1)H NMR spectroscopy can be a useful tool for monitoring cell response to different constraints. The use of spheroid suspensions seems to be a feasible alternative to localized spectroscopy since similar effects were found after radiation treatment. PMID- 27200295 TI - BRAF Mutation Is Associated with Improved Local Control of Melanoma Brain Metastases Treated with Gamma Knife Radiosurgery. AB - OBJECTIVES: Evidence has implicated a possible role of tumor mutation status on local control (LC) with radiotherapy. BRAF is a proto-oncogene that is mutated in approximately 50% of patients with melanoma. We sought to analyze the influence of BRAF status on LC of melanoma brain metastases (MBM) following Gamma Knife radiosurgery (GK). METHODS: Among 125 patients treated with GK for MBM at our institution between 2006 and 2015, we identified 19 patients with 69 evaluable metastases whose BRAF mutation status was known and follow-up imaging was available. LC of individual metastases was compared based on BRAF mutation status using statistical techniques to control for measurements of multiple metastases within each patient. CNS progression was defined as either local failure or development of new lesions. RESULTS: Of the 69 metastases, BRAF was mutated in 30 and wild-type in 39. With a median follow-up of 30 months for all patients and a median follow-up of 5.5 months for treated lesions, 1-year LC was significantly better among metastases with mutated vs. wild-type BRAF (69 vs. 34%, RR = 0.3, 95% CI = 0.1-0.7, p = 0.01). BRAF mutation was found to be a significant predictor of LC after stereotactic radiosurgery (SRS) in both univariate [RR = 0.3 (95% CI 0.1-0.7, p = 0.01)] and multivariate [RR = 0.2 (95% CI 0.1-0.7, p = 0.01)] analyses. There was also a trend toward improved CNS progression free survival (PFS) at 1 year (26 vs. 0%, p = 0.06), favoring BRAF-mutated patients. CONCLUSION: In this retrospective study, MBM treated with GK had significantly improved LC for patients with BRAF mutation vs. wild-type. Our data suggest that BRAF mutation may sensitize tumors to radiosurgery, and that BRAF wild-type tumors may be more radioresistant. PMID- 27200296 TI - Ovarian Cancer: The Fallopian Tube as the Site of Origin and Opportunities for Prevention. AB - High-grade serous carcinoma (HGSC) is the most common and aggressive histotype of epithelial ovarian cancer (EOC), and it is the predominant histotype associated with hereditary breast and ovarian cancer syndrome (HBOC). Mutations in BRCA1 and BRCA2 are responsible for most of the known causes of HBOC, while mutations in mismatch repair genes and several genes of moderate penetrance are responsible for the remaining known hereditary risk. Women with a history of familial ovarian cancer or with known germline mutations in highly penetrant genes are offered the option of risk-reducing surgery that involves the removal of the ovaries and fallopian tubes (salpingo-oophorectomy). Growing evidence now supports the fallopian tube epithelia as an etiological site for the development of HGSC and consequently, salpingectomy alone is emerging as a prophylactic option. This review discusses the site of origin of EOC, the rationale for risk-reducing salpingectomy in the high-risk population, and opportunities for salpingectomy in the low-risk population. PMID- 27200297 TI - Xerostomia after Radiotherapy for Oral and Oropharyngeal Cancer: Increasing Salivary Flow with Tasteless Sugar-free Chewing Gum. AB - INTRODUCTION: Radiation-induced xerostomia is a frequent late side effect after treatment for oral and oropharyngeal cancers. This may induce swallowing difficulties, compromised oral well-being, reduced nutrition intake, or speech deficiencies. Consequently, quality of life is often impaired for these patients. OBJECTIVES: The purpose of this study was to investigate the possibility to mechanically stimulate residual saliva function by using tasteless and sugar-free chewing gum. It was hypothesized that tasteless and sugar-free chewing gum could immediately increase salivary flow and potentially improve oral well-being when used on a regular basis. METHODS: From October to December 2014, 31 consecutive patients treated with primary radiotherapy (RT) and concomitant cisplatin (in locally advanced cases) for oral or oropharyngeal cancer consented to participate. All patients had finalized RT 2-8 months prior to participation and suffered from xerostomia. Samples of unstimulated and chewing gum-stimulated saliva were obtained at the entry into the study (Visit 1). For 2 weeks, patients used chewing gum on a regular basis whereupon saliva measurements were repeated to verify the changes (Visit 2). An abbreviated EORTC H&N35 questionnaire was completed for both visits. A small control group consisting of young and healthy individuals also tested the chewing gum. RESULTS: Twenty patients completed the study and an increase in saliva flow was observed for 14 patients. Before and after intervention with chewing gum, an increase in mean saliva output was seen between unstimulated and stimulated saliva for both Visit 1 and 2 (p = 0.008 and p = 0.05, respectively). No change in saliva output was seen in the control group. CONCLUSION: The chewing gum was able to stimulate saliva output that was seen at the beginning and at the end of the intervention. No improvement in baseline saliva was seen. Relevant changes in subjective measures of xerostomia were seen after 2 weeks of chewing the gum. PMID- 27200298 TI - Recent Advances in Targetable Therapeutics in Metastatic Non-Squamous NSCLC. AB - Lung adenocarcinoma is the most common subtype of non-small cell lung cancer (NSCLC). With the discovery of epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) rearrangements, and effective targeted therapies, therapeutic options are expanding for patients with lung adenocarcinoma. Here, we review novel therapies in non-squamous NSCLC, which are directed against oncogenic targets, including EGFR, ALK, ROS1, BRAF, MET, human epidermal growth factor receptor 2 (HER2), vascular endothelial growth factor receptor 2 (VEGFR2), RET, and NTRK. With the rapidly evolving molecular testing and development of new targeted agents, our ability to further personalize therapy in non-squamous NSCLC is rapidly expanding. PMID- 27200299 TI - Cullin 3 Ubiquitin Ligases in Cancer Biology: Functions and Therapeutic Implications. AB - Cullin-RING ubiquitin ligases are the largest E3 ligase family in eukaryotes and are multiprotein complexes. In these complexes, the Cullin protein serves as a scaffold to connect two functional modules of the ligases, the catalytic subunit and substrate-binding subunit. To date, eight members of the Cullin family proteins have been identified. In the Cul3 ubiquitin ligases, Bric-a brac/Tramtrack/Broad complex (BTB) domain-containing proteins function as a bridge to connect Cul3 and substrates. While the BTB domain is responsible for Cul3 binding, these proteins usually contain an additional domain for substrate interaction, such as MATH, kelch, Zn finger, and PAM, Highwire, and RPM-1 (PHR domain). With the existence of a large number of BTB proteins in human, the Cul3 ubiquitin ligases ubiquitinate a wide range of substrates involving in diverse cellular functions. In this review, we will discuss recent advances on the functions of Cul3 ubiquitin ligases in cancer development, progression, and therapeutic response and the dysregulation of Cul3-mediated ubiquitination events in human malignancies. In particular, we will focus on three Cul3 substrate adaptors, kelch-like ECH-associated protein (Keap1), kelch-like family member 20 (KLHL20), and speckle type BTB/POZ protein (SPOP), with the intent to highlight novel targets in cancer therapy. PMID- 27200300 TI - Intensity-Modulated Radiation Therapy with Stereotactic Body Radiation Therapy Boost for Unfavorable Prostate Cancer: The Georgetown University Experience. AB - PURPOSE/OBJECTIVES: Stereotactic body radiation therapy (SBRT) is emerging as a minimally invasive alternative to brachytherapy to deliver highly conformal, dose -escalated radiation therapy (RT) to the prostate. SBRT alone may not adequately cover the tumor extensions outside the prostate commonly seen in unfavorable prostate cancer. External beam radiation therapy (EBRT) with high dose rate brachytherapy boost is a proven effective therapy for unfavorable prostate cancer. This study reports on early prostate-specific antigen and prostate cancer specific quality of life (QOL) outcomes in a cohort of unfavorable patients treated with intensity-modulated radiation therapy (IMRT) and SBRT boost. MATERIALS/METHODS: Prostate cancer patients treated with SBRT (19.5 Gy in three fractions) followed by fiducial-guided IMRT (45-50.4 Gy) from March 2008 to September 2012 were included in this retrospective review of prospectively collected data. Biochemical failure was assessed using the Phoenix definition. Patients completed the expanded prostate cancer index composite (EPIC)-26 at baseline, 1 month after the completion of RT, every 3 months for the first year, then every 6 months for a minimum of 2 years. RESULTS: One hundred eight patients (4 low-, 45 intermediate-, and 59 high-risk) with median age of 74 years completed treatment, with median follow-up of 4.4 years. Sixty-four percent of the patients received androgen deprivation therapy prior to the initiation of RT. The 3-year actuarial biochemical control rates were 100 and 89.8% for intermediate- and high-risk patients, respectively. At the initiation of RT, 9 and 5% of men felt their urinary and bowel function was a moderate to big problem, respectively. Mean EPIC urinary and bowel function and bother scores exhibited transient declines, with subsequent return to near baseline. At 2 years posttreatment, 13.7 and 5% of men felt their urinary and bowel function was a moderate to big problem, respectively. CONCLUSION: At 3-year follow-up, biochemical control was favorable. Acute urinary and bowel symptoms were comparable to conventionally fractionated IMRT and brachytherapy. Patients recovered to near their baseline urinary and bowel function by 2 years posttreatment. A combination of IMRT with SBRT boost is well tolerated with minimal impact on prostate cancer-specific QOL. PMID- 27200301 TI - Transcriptional and Bioinformatic Analysis Provide a Relationship between Host Response Changes to Marek's Disease Viruses Infection and an Integrated Long Terminal Repeat. AB - GX0101, Marek's disease virus (MDV) strain with a long terminal repeat (LTR) insert of reticuloendotheliosis virus (REV), was isolated from CVI988/Rispens vaccinated birds showing tumors. We have constructed a LTR deleted strain GX0101DeltaLTR in our previous study. To compare the host responses to GX0101 and GX0101DeltaLTR, chicken embryo fibroblasts (CEF) cells were infected with two MDV strains and a gene-chip containing chicken genome was employed to examine gene transcription changes in host cells in the present study. Of the 42,368 chicken transcripts on the chip, there were 2199 genes that differentially expressed in CEF infected with GX0101 compared to GX0101DeltaLTR significantly. Differentially expressed genes were distributed to 25 possible gene networks according to their intermolecular connections and were annotated to 56 pathways. The insertion of REV LTR showed the greatest influence on cancer formation and metastasis, followed with immune changes, atherosclerosis, and nervous system disorders in MDV-infected CEF cells. Based on these bio functions, GX0101 infection was predicated with a greater growth and survival inhibition but lower oncogenicity in chickens than GX0101DeltaLTR, at least in the acute phase of infection. In summary, the insertion of REV LTR altered the expression of host genes in response to MDV infection, possibly resulting in novel phenotypic properties in chickens. Our study has provided the evidence of retroviral insertional changes of host responses to herpesvirus infection for the first time, which will promote to elucidation of the possible relationship between the LTR insertion and the observed phenotypes. PMID- 27200302 TI - Characterization of Spbhp-37, a Hemoglobin-Binding Protein of Streptococcus pneumoniae. AB - Streptococcus pneumoniae is a Gram-positive microorganism that is the cause of bacterial pneumonia, sinusitis and otitis media. This human pathogen also can cause invasive diseases such as meningitis, bacteremia and septicemia. Hemoglobin (Hb) and haem can support the growth and viability of S. pneumoniae as sole iron sources. Unfortunately, the acquisition mechanism of Hb and haem in this bacterium has been poorly studied. Previously we identified two proteins of 37 and 22 kDa as putative Hb- and haem-binding proteins (Spbhp-37 and Spbhp-22, respectively). The sequence of Spbhp-37 protein was database annotated as lipoprotein without any function or localization. Here it was immunolocalized in the surface cell by transmission electron microscopy using specific antibodies produced against the recombinant protein. The expression of Spbhp-37 was increased when bacteria were grown in media culture supplied with Hb. In addition, the affinity of Sphbp-37 for Hb was determined. Thus, in this work we are presenting new findings that attempt to explain the mechanism involved in iron acquisition of this pathogen. In the future these results could help to develop new therapy targets in order to avoid the secondary effects caused by the traditional therapies. PMID- 27200303 TI - Induction of Central Host Signaling Kinases during Pneumococcal Infection of Human THP-1 Cells. AB - Streptococcus pneumoniae is a widespread colonizer of the mucosal epithelia of the upper respiratory tract of human. However, pneumococci are also responsible for numerous local as well as severe systemic infections, especially in children under the age of five and the elderly. Under certain conditions, pneumococci are able to conquer the epithelial barrier, which can lead to a dissemination of the bacteria into underlying tissues and the bloodstream. Here, specialized macrophages represent an essential part of the innate immune system against bacterial intruders. Recognition of the bacteria through different receptors on the surface of macrophages leads thereby to an uptake and elimination of bacteria. Accompanied cytokine release triggers the migration of leukocytes from peripheral blood to the site of infection, where monocytes differentiate into mature macrophages. The rearrangement of the actin cytoskeleton during phagocytosis, resulting in the engulfment of bacteria, is thereby tightly regulated by receptor-mediated phosphorylation cascades of different protein kinases. The molecular cellular processes including the modulation of central protein kinases are only partially solved. In this study, the human monocytic THP 1 cell line was used as a model system to examine the activation of Fcgamma and complement receptor-independent signal cascades during infection with S. pneumoniae. Pneumococci cultured either in chemically defined or complex medium showed no significant differences in pneumococcal phagocytosis by phorbol 12 myristate 13-acetate (PMA) differentiated THP-1 cells. Double immuno-fluorescence microscopy and antibiotic protection assays demonstrated a time-dependent uptake and killing of S. pneumoniae 35A inside of macrophages. Infections of THP-1 cells in the presence of specific pharmacological inhibitors revealed a crucial role of actin polymerization and importance of the phosphoinositide 3-kinase (PI3K) and Protein kinase B (Akt) as well during bacterial uptake. The participation of essential host cell signaling kinases in pneumococcal phagocytosis was deciphered for the kinase Akt, ERK1/2, and p38 and phosphoimmunoblots showed an increased phosphorylation and thus activation upon infection with pneumococci. Taken together, this study deciphers host cell kinases in innate immune cells that are induced upon infection with pneumococci and interfere with bacterial clearance after phagocytosis. PMID- 27200304 TI - Modular Organization of the ESX-5 Secretion System in Mycobacterium tuberculosis. AB - Mycobacteria utilize type VII secretion systems (T7SS) to export many of their important virulence proteins. The T7SS encompasses five homologous secretion systems (ESX-1 to ESX-5). Most pathogenic mycobacterial species, including the human pathogen Mycobacterium tuberculosis, possess all five ESX systems. The ESX 1, -3, and -5 systems are important for virulence of mycobacteria but the molecular mechanisms of their secretion apparatus and the identity and activity of secreted effector proteins are not well characterized. The different ESX systems show similarities in gene composition due to their common phylogenetic origin but recent studies demonstrate mechanistic as well as functional variations between the systems. For example, the ESX-1 system is involved in lysis of the phagosomal membrane and phagosomal escape of the bacteria while the ESX-5 system is required for mycobacterial cell wall stability and host cell lysis. Mechanistically, the ESX-1 substrates show interdependence during secretion while the ESX-5 system may use a duplicated four-gene region (ESX-5a) as an accessory system for transport of a subset of proteins of the ESX-5 secretome. In the present review we will provide an overview of the molecular components of the T7SS and their function with a particular focus on the ESX-5 system. PMID- 27200306 TI - The risk of emergency cesarean section after failure of vaginal delivery according to prepregnancy body mass index or gestational weight gain by the 2009 Institute of Medicine guidelines. AB - OBJECTIVE: To evaluate the risk of emergency cesarean section according to the prepregnancy body mass index (BMI) and gestational weight gain per the 2009 Institute of Medicine guidelines. METHODS: A retrospective analysis of data from 2,765 women with singleton full-term births (2009 to 2012) who attempted a vaginal delivery was conducted. Pregnancies with preeclampsia, chronic hypertension, diabetes, planned cesarean section, placenta previa, or cesarean section due to fetal anomalies or intrauterine growth restriction were excluded. Odds ratios (ORs) and confidence intervals (CIs) for emergency cesarean section were calculated after adjusting for prepregnancy BMI or gestational weight gain. RESULTS: Three-hundred and fifty nine (13.0%) women underwent emergency cesarean section. The adjusted OR for overweight, obese, and extremely obese women indicated a significantly increased risk of cesarean delivery. Gestational weight gain by Institute of Medicine guidelines was not associated with an increased risk of cesarean delivery. However, inadequate and excessive weight gain in obese women was highly associated with an increased risk of emergency cesarean section, compared to these in normal BMI (OR, 5.56; 95% CI, 1.36 to 22.72; OR, 3.63; 95% CI, 1.05 to 12.54; respectively), while there was no significant difference between normal BMI and obese women with adequate weight gain. CONCLUSION: Obese women should be provided special advice before and during pregnancy for controlling weight and careful consideration should be needed at the time of vaginal delivery to avoid emergency cesarean section. PMID- 27200305 TI - A review of the epidemiology and treatment of Peyronie's disease. AB - INTRODUCTION: Peyronie's disease (PD) has significant effect on patients and their partners. We provide a current review of the epidemiology as well as the nonsurgical and surgical treatment of PD. MATERIALS AND METHODS: Review of literature pertaining to PD with focus on epidemiology and treatment options. CONCLUSION: PD is common and likely underreported. The availability of new and highly effective treatment options will catalyze patient awareness and subsequently the prevalence of disease. PMID- 27200307 TI - How high is too high in cutoff levels from 50-g glucose challenge test. AB - OBJECTIVE: To determine the highest 50-g glucose challenge test (GCT) value that indicates no further diagnostic test is needed to confirm a diagnosis of gestational diabetes mellitus (GDM) under the criteria of National Diabetes Data Group (NDDG) or the Carpenter and Coustan (C&C) and fasting glucose thresholds from the International Association of Diabetes and Pregnancy Study Group (IADPSG). METHODS: We collected the 50-g GCT results from 16,560 pregnancies and identified 2,457 gravidas with positive 50-g GCT (>=130 mg/dL) values who underwent the 100-g glucose tolerance test. We investigated GDM prevalence in pregnancies with positive 50-g GCT according to the respective diagnostic thresholds and determined the 50-g GCT cutoff values with 100% positive predictive value for GDM under each diagnostic threshold. RESULTS: Twelve point five percent (306/2,457), 20.0% (492/2,457), and 9.6% (235/2,457) met the diagnostic criteria of GDM with the application of NDDG, C&C criteria, and fasting glucose thresholds from IADPSG (>=92 mg/dL), respectively. We also found that the prevalence of GDM increased with increasing 50-g GCT values using each diagnostic criterion. Importantly, we identified that all subjects with a 50-g GCT value >=223, >=217, or >=228 mg/dL can be exclusively diagnosed as having gestational diabetes according to the criteria of NDDG, C&C, and fasting glucose thresholds from IADPSG, respectively. CONCLUSION: We propose that women with a 50 g GCT screening value >=228 mg/dL can be reliably omitted from further confirmative tests for GDM, such as 100- or 75-g glucose tolerance test. PMID- 27200308 TI - The influence of number of high risk factors on clinical outcomes in patients with early-stage cervical cancer after radical hysterectomy and adjuvant chemoradiation. AB - OBJECTIVE: The purpose of this study was to evaluate the prognosis according to the number of high risk factors in patients with high risk factors after radical hysterectomy and adjuvant chemoradiation therapy for early stage cervical cancer. METHODS: Clinicopathological variables and clinical outcomes of patients with FIGO (International Federation of Gynecology and Obstetrics) stage IB1 to IIA cervical cancer who had one or more high risk factors after radical hysterectomy and adjuvant chemoradiation therapy were retrospectively analyzed. Patients were divided into two groups according to the number of high risk factors (group 1, single high risk factor; group 2, two or more high risk factors). RESULTS: A total of 93 patients were enrolled in the present study. Forty nine out of 93 (52.7%) patients had a single high risk factor, and 44 (47.3%) had two or more high risk factors. Statistically significant differences in stage and stromal invasion were observed between group 1 and group 2. However, age, histology, tumor size, and lymphovascular space invasion did not differ significantly between the groups. Distant recurrence occurred more frequently in group 2, and the probability of recurrence and death was higher in group 2. CONCLUSION: Patients with two or more high risk factors had worse prognosis in early stage cervical cancer. For these patients, consideration of new strategies to improve survival may be worthwhile. Conduct of further clinical trials is warranted for development of adjuvant treatment strategies individualized to each risk group. PMID- 27200309 TI - Endometrial evaluation with transvaginal ultrasonography for the screening of endometrial hyperplasia or cancer in premenopausal and perimenopausal women. AB - OBJECTIVE: The aim of our study is to determine clinical factors and sonographic findings associated with endometrial hyperplasia or cancer (EH+) in premenopausal and perimenopausal women. METHODS: A total of 14,340 transvaginal ultrasonography examinations of 9,888 healthy premenopausal and perimenopausal women were included in this retrospective study. One hundred sixty-two subjects underwent endometrial biopsy based on abnormal uterine bleeding (AUB), sonographic endometrial abnormalities (thickened endometrium, endometrial mass, or endometrial stripe abnormality), or both. The clinical factors and sonographic endometrial abnormalities were evaluated with regard to EH+. RESULTS: Histologically verified EH+ was found in fourteen subjects (8.6%); ten cases of endometrial hyperplasia (EH) without atypia, three cases of EH with atypia (AEH), and one case of endometrial cancer. Neither clinical factors nor AUB were associated with EH+ (P=0.32) or AEH+ (P=0.72). Of sonographic findings, endometrial stripe abnormality was significantly associated with EH+ (P=0.003) and marginally associated with AEH+ (P=0.05), but a thickened endometrium was not associated with EH+ (P=0.43). CONCLUSION: Endometrial stripe abnormality is a significant factor to predict EH+ in healthy premenopausal and perimenopausal women with and without AUB. However, simple measurement of endometrial thickness has a limited role in this capacity. PMID- 27200311 TI - A clinical study on the trocar-guided mesh repair system for pelvic organ prolapse surgery. AB - OBJECTIVE: To evaluate the complication and recurrence rates in patients undergoing trocar-guided mesh implant for pelvic organ prolapse (POP) treatment. METHODS: A retrospective study was performed based on the medical records of patients who had undergone mesh implant by one surgeon from May 2006 to August 2013 at the Presbyterian Medical Center in Korea. We evaluated perioperative complications such as bladder injury, mesh exposure, urinary symptoms, infections, and chronic pelvic pain. Recurrence was defined as a POP quantification system stage >=II or any symptomatic prolapse. RESULTS: Sixty seven patients were evaluated, and the mean age of patients was 65.4+/-7.2 years. Stage >=III POP-quantification Ba was noted in 61 patients (91%). Intraoperative complications included three cases of bladder injury (4.5%). The mean follow-up period was 44.1+/-7.9 months. Postoperative complications occurred in seven women (10.5%): four cases of urinary symptoms (6%), two cases of infections (3%), and one case of chronic pelvic pain (1.5%). Mesh exposure did not occur (0%). Prolapse recurrence was reported in five patients (7.5%). CONCLUSION: Based on our operational result, the trocar-guided mesh implant seems to provide safe and effective outcomes. PMID- 27200310 TI - Efficacy of hyaluronan-rich transfer medium on implantation and pregnancy rates in fresh and frozen-thawed blastocyst transfers in Korean women with previous implantation failure. AB - OBJECTIVE: To evaluate the effect of hyaluronan-rich transfer medium on pregnancy and implantation rates in fresh and frozen-thawed embryo transfers in Korean women with previous implantation failure. METHODS: This retrospective study included 283 blastocyst transfers in patients with previous embryo transfer failure at a private fertility clinic. In the study group (n=88), blastocyst transfers were performed using an hyaluronan-rich transfer medium prior to transfer, whereas blastocyst transfers without any treatment served as controls (n=195). According to the type of transfer (fresh elective or frozen-thawed), all the blastocyst transfers were divided into two study and two control groups. RESULTS: The patient's mean age, serum anti-Mullerian hormone level, causes of infertility, embryo quality, and the number of transferred embryos were comparable between the study and control groups. There were no significant differences in clinical pregnancy rate (45.5% vs. 43.1%), implantation rate (28.9% vs. 28.8%), and clinical abortion rate (10.0% vs. 8.3%) between the two groups, and these findings were not changed after subgroup analysis according to the type of transfer. CONCLUSION: The use of hyaluronan-rich transfer medium in the blastocyst transfer does not appear to have any significant effect on the implantation and pregnancy rates in patients with previous implantation failure. PMID- 27200312 TI - The association of pelvic organ prolapse severity and improvement in overactive bladder symptoms after surgery for pelvic organ prolapse. AB - OBJECTIVE: The purpose of this study was to evaluate the impact of pelvic organ prolapse (POP) repair on overactive bladder (OAB) symptoms in women with POP and the effect of baseline POP severity on improvement in OAB after surgical repair of POP. And we also tried to identify any preoperative factors for persistent postoperative OAB symptoms. METHODS: A total of 87 patients with coexisting POP and OAB who underwent surgical correction of POP were included and retrospectively analyzed and postoperative data was obtained by telephone interview. OAB was defined as an affirmative response to item no. 15 (urinary frequency) and item no. 16 (urge incontinence) of the Pelvic Floor Distress Inventory. POP severity was dichotomized by Pelvic Organ Prolapse Quantification stage 1 to 2 (n=22) versus stage 3 to 4 (n=65). RESULTS: OAB symptoms were significantly improved after surgical treatment (P<0.001). But there was no significant differences in postoperative improvement of frequency and urge incontinence between stage 1 to 2 group versus stage 3 to 4 group. Preoperative demographic factors (age, parity, and POP stage) were not significantly related to persistent postoperative OAB symptoms. CONCLUSION: Women with coexisting POP and OAB who undergo surgical repair experience significant improvement in OAB symptoms after surgery, but severity of POP had no significant difference in improvement of OAB symptoms. Postoperative persistent OAB symptoms were not related to age, parity, body mass index, and POP stage. PMID- 27200313 TI - Role of vaginal estradiol pretreatment combined with vaginal misoprostol for cervical ripening before operative hysteroscopy in postmenopausal women. AB - OBJECTIVE: To assess the efficacy and safety of vaginal misoprostol after a pretreatment with vaginal estradiol to facilitate the hysteroscopic surgery in postmenopausal women. METHODS: In this observational comparative study, 35 control women (group A) did not receive any pharmacological treatment,26 women (group B) received 25 ug of vaginal estradiol daily for 14 days and 400 ug of vaginal misoprostol 12 hours before hysteroscopic surgery, 32 women (group C) received 400 ug of vaginal misoprostol 12 hours before surgery. RESULTS: Demographic data were well balanced and all variables were not significantly different among the three groups. The study showed a significant difference in the preoperative cervical dilatation among the group B (7.09+/-1.87 mm), the group A (5.82+/-1.85 mm; B vs. A, P=0.040) and the group C (5.46+/-2.07 mm; B vs. C, P=0.007). The dilatation was very easy in 73% of women in group B. The pain scoring post surgery was lower in the group B (B vs. A, P=0.001; B vs. C, P=0.077). In a small subgroup of women with suspected cervical stenosis, there were no statistically significant differences among the three groups considered. No complications during and post hysteroscopy were observed. CONCLUSION: In postmenopausal women the pretreatment with oestrogen appears to have a crucial role in allowing the effect of misoprostol on cervical ripening. The combination of vaginal estradiol and vaginal misoprostol presents minor side effects and has proved to be effective in obtaining satisfying cervical dilatation thus significantly reducing discomfort for the patient. PMID- 27200314 TI - Development and validation of novel digitalized cervicography system. AB - OBJECTIVE: Digital cervicography systems would be expected to reduce the costs of film cervicography, and provide the opportunity for "telemedicine-based" screening. We aimed to develop web-based digital cervicography system, and validate it compared with conventional film cervicography. METHODS: A hundred cases from five centers were prospectively included, and cervical images (analogue, digitalized by scanning analogue, and digital) were taken separately using both analogue (Cerviscope) and digital camera (Dr. Cervicam) in each patient. Nine specialists evaluated the three kinds of images of each case with time interval between evaluations of each image. To validate novel digitalized system, we analyzed intra-observer variance among evaluation results of three kinds of images. RESULTS: Sixty-three cases were finally analyzed after excluding technically defective cases that cannot be evaluable on analogue images. The generalized kappa for analogue versus digital image was 0.83, for analogue versus scanned image 0.72, and for digital versus scanned image was 0.71; all were in excellent consensus. CONCLUSION: Digitalized cervicography system can be substituted for the film cervicography very reliably, and can be used as a promising telemedicine tool for cervical cancer screening. PMID- 27200316 TI - Prenatal diagnosis of fetal adrenal hemorrhage and endocrinologic evaluation. AB - We present a case of a fetal adrenal hemorrhage, a rare disease in fetal life, detected prenatally at 36 weeks' gestation by ultrasound. Routine ultrasound examination at 36 weeks' gestation by primary obstetrician showed a cyst on the fetal suprarenal area. Initially, the suspected diagnosis was a fetal adrenal hemorrhage, but we should diagnose differently from neuroblastoma. Subsequent ultrasound examination at 38 and 39 weeks' gestation showed increase of the cyst in size. A 3.34-kg-male neonate was born by spontaneous vaginal delivery at 39 weeks' gestation. The diagnosis of adrenal hemorrhage was confirmed by postnatal follow-up sonograms and magnetic resonance imaging. Course and sonographic signs were typical for adrenal hemorrhage and the neonate was therefore managed without surgical exploration. PMID- 27200315 TI - Chorioamniotic membrane separation caused by the seromucinous collection from a placental chorioangioma. AB - Placental chorioangioma is a benign non-trophoblastic tumor of the placenta that can have various adverse effects on the mother and fetus depending on its size. Chorioamniotic membrane separation is rare condition of detachment between the amniotic membrane and chorionic membrane. Chorioamniotic membrane separation after the second trimester of pregnancy is usually occurs after invasive procedures or may occur spontaneously; it is mostly associated with fetal abnormalities. Here, we report a case of chorioamniotic membrane separation that might be occurred caused by the seromucinous secretion from a placental chorioangioma. PMID- 27200317 TI - Uterine prolapse in a primigravid woman. AB - Uterine prolapse during pregnancy is an uncommon condition. It can cause preterm labor, spontaneous abortion, fetal demise, maternal urinary complication, maternal sepsis and death. We report the case of uterine prolapse in a 32-year old healthy primigravid woman. She had no risk factors associated with uterine prolapse. She was conservatively treated, resulting in a successful vaginal delivery. This report is a very rare case of uterine prolapse in a young healthy primigravid woman, resulting in a successful vaginal delivery. PMID- 27200318 TI - Concomitant ultrasound-guided intra-gestational sac methotrexate-potassium chloride and systemic methotrexate injection in the recurrent cesarean scar pregnancy. AB - Recurrent ectopic pregnancy of cesarean scar is very rare and its therapeutic management is still not established. We reported the first case of recurrent cesarean scar pregnancy that was successfully treated with concomitant intra gestational sac methotrexate-potassium chloride injection and systemic methotrexate injection. This case study provides physicians with a safe and effective minimally invasive treatment option for recurrent cesarean scar pregnancy. PMID- 27200320 TI - Work-Life Balance: The True Failure Is in Not Trying. PMID- 27200319 TI - Delayed retropneumoperitoneum following vaginal laceration in a 7-year-old girl. AB - We describe an unusual case of delayed retropneumoperitoneum caused by a deep vaginal laceration as a result trauma from a water jet in a fountain. A 7-year old premenarcheal girl presented to the emergency department after experiencing an injury from a water jet at a fountain park. Initially, the patient's vital sign and perineum were within normal range. Because the patient's vital signs became unstable 12 hours after vaginal injury, we carried out abdomino-pelvic computed tomography resulting in retropneumoperitoneum. Arterial bleeding from vaginal lateral wall was founded and controlled by electrocoagulation. No damage to the rectum was laparoscopically confirmed. A diagnostic laparoscopy, not laparotomy, should be considered in cases of retropneumoperitoneum with an ambiguous cause first. PMID- 27200321 TI - Work-Life Balance: How Can We Achieve It within the Work Environment? PMID- 27200323 TI - Sonographic Renal Parenchymal Measurements for the Evaluation and Management of Ureteropelvic Junction Obstruction in Children. AB - PURPOSE: To correlate sonographic renal parenchymal measurements among patients with ureteropelvic junction obstruction (UPJO) labeled society of fetal urology (SFU) hydronephrosis grades 1-4 and to examine whether sonographic renal parenchymal measurements could be used to differentiate conservative vs. surgical management. MATERIALS AND METHODS: Retrospective chart review and sonographic renal parenchymal measurements (renal length, medullary pyramid thickness, and renal parenchymal thickness) were performed in patients with SFU grades 1-4 hydronephrosis secondary to UPJO managed between 2009 and 2014. Exclusion criteria included other concomitant genitourinary pathology or incomplete follow up. Anterior-posterior renal pelvic diameter (APRPD) and radionuclide renography were also evaluated when available. RESULTS: One hundred four patients with UPJO underwent 244 renal and bladder ultrasound (1,464 sonographic renal parenchymal measurements in 488 kidneys). Medullary pyramid thickness and renal parenchymal thickness progressively decreased from SFU grades 1-4 (p < 0.05). A similar trend was appreciated when comparing SFU grades 1 and 2 vs. 3 and 4, as well as SFU grades 3 vs. 4 (p < 0.05). SFU grade 3 and 4 patients who underwent pyeloplasty had longer renal length in comparison to those who were managed conservatively (p < 0.02). CONCLUSION: This is the first study that evaluates these objective, quantifiable sonographic renal parenchymal measurements in children with unilateral UPJO. These sonographic renal parenchymal measurements correlate closely with worsening of hydronephrosis graded by the SFU and APRPD classification systems. Prospective studies are needed to elucidate the role of sonographic renal parenchymal measurements in the management of children with UPJO. PMID- 27200322 TI - Does Preputial Reconstruction Increase Complication Rate of Hypospadias Repair? 20-Year Systematic Review and Meta-Analysis. AB - INTRODUCTION: We performed a systematic review of the literature on preputial reconstruction (PR) during hypospadias repair to determine the cumulative risk of preputial skin complications and the influence of PR on urethroplasty complications, namely, fistula formation and overall reoperation rate of the repair. MATERIALS AND METHODS: A systematic search of the literature published after 06/1995 was performed in 06/2015 using the keyword "hypospadias." Only studies on the outcome of PR in children, defined as dehiscence of the reconstructed prepuce or secondary phimosis needing circumcision, were selected. A meta-analysis of studies comparing PR vs. circumcision was performed for the outcomes "hypospadias fistula formation" and "reoperation rate." RESULTS: Twenty studies were identified. Nineteen reported the outcome of PR in 2115 patients. Overall, 95% (2016/2115) of patients undergoing PR had distal hypospadias. The cumulative rate of PR complications was 7.7% (163/2115 patients), including 5.7% (121/2115 patients) preputial dehiscences and 1.5% (35/2117 reported patients) secondary phimoses needing circumcision. A meta-analysis of seven studies comparing patients undergoing PR vs. circumcision showed no increased risk of urethral fistula formation associated with PR, odds ratio (OR) (Mantel-Haenszel, Fixed effect, 95% CI), 1.25 (0.80-1.97). Likewise, two studies comparing the overall reoperation rate did not show an increased risk of reoperation associated with PR, OR (Mantel-Haenszel, Random effect, 95% CI), 1.27 (0.45-3.58). CONCLUSION: PR carries an 8% risk of specific complications (dehiscence of reconstructed prepuce or secondary phimosis needing circumcision), but does not seem to increase the risk of urethroplasty complications, and the overall reoperation rate of hypospadias repair. PMID- 27200325 TI - Dietary Alpha-Lipoic Acid Alters Piglet Neurodevelopment. AB - INTRODUCTION: Alpha-lipoic acid (a-LA) is an antioxidant shown to ameliorate age associated impairments of brain and cardiovascular function. Human milk is known to have high antioxidant capacity; however, the role of antioxidants in the developing brain is largely uncharacterized. This exploratory study aimed to examine the dose-response effects of a-LA on piglet growth and neurodevelopment. METHODS: Beginning at 2 days of age, 31 male pigs received 1 of 3 diets: control (CONT) (0 mg a-LA/100 g), low a-LA (LOW) (120 mg a-LA/100 g), or high a-LA (HIGH) (240 mg a-LA/100 g). From 14 to 28 days of age, pigs were subjected to spatial T maze assessment, and macrostructural and microstructural neuroimaging procedures were performed at 31 days of age. RESULTS: No differences due to diet were observed for bodyweight gain or intestinal weight and length. Spatial T-maze assessment did not reveal learning differences due to diet in proportion of correct choices or latency to choice measures. Diffusion tensor imaging revealed decreased (P = 0.01) fractional anisotropy (FA) in the internal capsule of HIGH fed pigs compared with both the CONT (P < 0.01)- and LOW (P = 0.03)-fed pigs, which were not different from one another. Analysis of axial diffusivity (AD) within the internal capsule revealed a main effect of diet (P < 0.01) in which HIGH-fed piglets exhibited smaller (P < 0.01) rates of diffusion compared with CONT piglets, but HIGH-fed piglets were not different (P = 0.12) than LOW-fed piglets. Tract-based spatial statistics, a comparison of FA values along white matter tracts, revealed 1,650 voxels where CONT piglets exhibited higher (P < 0.05) values compared with HIGH-fed piglets. CONCLUSION: The lack of differences in intestinal and bodyweight measures among piglets indicate a-LA supplementation does not impact overall growth, regardless of concentration. Additionally, no observed differences between CONT- and LOW-fed piglets in behavior and neuroimaging measures indicate a low concentration of a-LA does not affect normal brain development. Supplementation of a-LA at a high concentration appeared to alter white matter maturation in the internal capsule, which may indicate delayed neurodevelopment in these piglets. PMID- 27200324 TI - Rationale for Implementation of Warm Cardiac Surgery in Pediatrics. AB - Cardiac surgery was developed thanks to the introduction of hypothermia and cardiopulmonary bypass in the early 1950s. The deep hypothermia protective effect has been essential to circulatory arrest complex cases repair. During the early times of open-heart surgery, a major concern was to decrease mortality and to improve short-term outcomes. Both mortality and morbidity dramatically decreased over a few decades. As a consequence, the drawbacks of deep hypothermia, with or without circulatory arrest, became more and more apparent. The limitation of hypothermia was particularly evident for the brain and regional perfusion was introduced as a response to this problem. Despite a gain in popularity, the results of regional perfusion were not fully convincing. In the 1990s, warm surgery was introduced in adults and proved to be safe and reliable. This option eliminates the deleterious effect of ischemia-reperfusion injuries through a continuous, systemic coronary perfusion with warm oxygenated blood. Intermittent warm blood cardioplegia was introduced later, with impressive results. We were convinced by the easiness, safety, and efficiency of warm surgery and shifted to warm pediatric surgery in a two-step program. This article outlines the limitations of hypothermic protection and the basic reasons that led us to implement pediatric warm surgery. After tens of thousands of cases performed across several centers, this reproducible technique proved a valuable alternative to hypothermic surgery. PMID- 27200326 TI - Overview of C3 Glomerulopathy. AB - C3 glomerulopathy is an umbrella term, which includes several rare forms of glomerulonephritis (GN) with underlying defects in the alternate complement cascade. A common histological feature noted in all these GN is dominant C3 deposition in the glomerulus. In this review, we will provide an overview of the complement system as well as mediators, with an introduction to pharmaceutical agents that can alter the pathway. PMID- 27200327 TI - Estimating Active Transportation Behaviors to Support Health Impact Assessment in the United States. AB - Health impact assessment (HIA) has been promoted as a means to encourage transportation and city planners to incorporate health considerations into their decision-making. Ideally, HIAs would include quantitative estimates of the population health effects of alternative planning scenarios, such as scenarios with and without infrastructure to support walking and cycling. However, the lack of baseline estimates of time spent walking or biking for transportation (together known as "active transportation"), which are critically related to health, often prevents planners from developing such quantitative estimates. To address this gap, we use data from the 2009 US National Household Travel Survey to develop a statistical model that estimates baseline time spent walking and biking as a function of the type of transportation used to commute to work along with demographic and built environment variables. We validate the model using survey data from the Raleigh-Durham-Chapel Hill, NC, USA, metropolitan area. We illustrate how the validated model could be used to support transportation related HIAs by estimating the potential health benefits of built environment modifications that support walking and cycling. Our statistical model estimates that on average, individuals who commute on foot spend an additional 19.8 (95% CI 16.9-23.2) minutes per day walking compared to automobile commuters. Public transit riders walk an additional 5.0 (95% CI 3.5-6.4) minutes per day compared to automobile commuters. Bicycle commuters cycle for an additional 28.0 (95% CI 17.5-38.1) minutes per day compared to automobile commuters. The statistical model was able to predict observed transportation physical activity in the Raleigh-Durham-Chapel Hill region to within 0.5 MET-hours per day (equivalent to about 9 min of daily walking time) for 83% of observations. Across the Raleigh Durham-Chapel Hill region, an estimated 38 (95% CI 15-59) premature deaths potentially could be avoided if the entire population walked 37.4 min per week for transportation (the amount of transportation walking observed in previous US studies of walkable neighborhoods). The approach developed here is useful both for estimating baseline behaviors in transportation HIAs and for comparing the magnitude of risks associated with physical inactivity to other competing health risks in urban areas. PMID- 27200328 TI - Alignment of Epidemiology Practice and Academic Competencies through Effective Collaboration. AB - BACKGROUND: Online learning has recently garnered increased attention as technology use in the classroom grows. However, most of the published approaches regarding this topic in postgraduate education centers on clinical environments. Models of partnerships between applied public health agencies and academic centers to produce mutually beneficial online learning opportunities for graduate level public health courses have not been explored in the literature. METHODS: East Tennessee State University (ETSU) and the Tennessee Department of Health (TDH) partnered to build three online, asynchronous epidemiology modules for an interdisciplinary audience of graduate students. The goals of the modules were to (1) introduce students to a public health issue, (2) provide students with hands on learning about data and information available through TDH, and (3) allow students to connect theory to practice by having them create a product for use by TDH. TDH created topic-specific modules that would be used within the infectious disease, chronic disease, and cancer epidemiology courses, and piloted during the 2015-2016 academic term. RESULTS: Conference calls between the two institutions occurred in the spring and the summer of 2015. Two of the three epidemiology modules were presented to ETSU staff for critique and edits at an in-person meeting during the summer. The methods of delivery for each section within a module varied from recorded webinar format to self-guided instruction. One module utilized available learning tools provided by the Centers of Disease Control and Prevention, while the other module was constructed entirely using TDH data. Both modules included various exercises and assignments to be conducted in class and as homework and concluded with the student being asked to construct a learning product as a final project. The ETSU-TDH team decided that this learning product would be provided back to TDH for possible future use. DISCUSSION: The innovative partnership between a state government agency and an academic institution has demonstrated the need for such collaborations in public health. Understanding how applied public health practice would utilize what is learned in the classroom and preparing students for real-world application may be the missing link between theory and practice. PMID- 27200329 TI - Comparing Efficacy of Online and In-Person Versions of a Training on U.S. Federal Wage and Hour, Child Labor Laws, and Hazardous Occupations Orders for Secondary School Professionals. AB - BACKGROUND: The New Jersey Safe Schools Program (NJSS) offers courses required for secondary school vocational-career-technical education teachers to become school-sponsored structured learning experience supervisors. The "Federal Wage and Hour and Child Labor Laws, Regulations and Hazardous Order Course" (FWH) was originally conducted in-person by U.S. Department of Labor-Wage and Hour Division from 2005 to Summer 2013, and then NJSS began conducting this course in-person (October 2013-April 2015). Staring in March 2015, this course was conducted online; beta-/pilot tests were conducted in Winter 2014-2015. Starting in May 2015, this course was offered exclusively online. This paper analyzes data from the in-person and online versions of the FWH, including overall course evaluation data comparing two versions with similar questions/constructs. METHODS: The New Jersey Safe Schools Program modifications to FWH included adding information regarding the Fair Labor Standards Act's Section 14(c) and supplemental case studies. The online version included information/resources provided during the in person training plus assessments to supplement each module; the online version was split into modules to allow participants scheduling flexibility. Participants were given multiple possible attempts to achieve a minimum passing grade of 70%, excluding two ungraded activities (crossword puzzles simply completed). Descriptive statistics evaluated user satisfaction online compared to the in person version of FWH and performance on aforementioned online assessments replacing in-person discussions/interactions. RESULTS: Between October 2013 and April 2015, 160 participants completed the training in person; 156 had complete data. Between April and November 2015, 78 participants completed the training online; 74 participants had complete data. Other enrolled participants were in progress (not done as of 12/23/2015). Overall satisfaction was similarly high for in-person and online versions of FWH; over 95% of responding participants recommended this course to colleagues. Course evaluations for in-person participants indicated 83% felt the course objectives were completely met, whereas 95% of the responding online cohort felt course objectives were completely met. Further analyses examined performance of online assessments regarding number of attempts and scores achieved and performance on highlighted questions in certain module lessons. CONCLUSION: Data suggested the online format as a viable alternative to an in-person version of this training and provided NJSS and agency partners with ideas on how modifications/improvements can be made. PMID- 27200330 TI - Factors Associated with Recent HIV Testing among Heterosexuals at High Risk for HIV Infection in New York City. AB - BACKGROUND: The Centers for Disease Control and Prevention recommends persons at high risk for HIV infection in the United States receive annual HIV testing to foster early HIV diagnosis and timely linkage to health care. Heterosexuals make up a significant proportion of incident HIV infections (>25%) but test for HIV less frequently than those in other risk categories. Yet factors that promote or impede annual HIV testing among heterosexuals are poorly understood. The present study examines individual/attitudinal-, social-, and structural-level factors associated with past-year HIV testing among heterosexuals at high risk for HIV. METHODS: Participants were African-American/Black and Hispanic heterosexual adults (N = 2307) residing in an urban area with both high poverty and HIV prevalence rates. Participants were recruited by respondent-driven sampling in 2012-2015 and completed a computerized structured assessment battery covering background factors, multi-level putative facilitators of HIV testing, and HIV testing history. Separate logistic regression analysis for males and females identified factors associated with past-year HIV testing. RESULTS: Participants were mostly male (58%), African-American/Black (75%), and 39 years old on average (SD = 12.06 years). Lifetime homelessness (54%) and incarceration (62%) were common. Half reported past-year HIV testing (50%) and 37% engaged in regular, annual HIV testing. Facilitators of HIV testing common to both genders included sexually transmitted infection (STI) testing or STI diagnosis, peer norms supporting HIV testing, and HIV testing access. Among women, access to general medical care and extreme poverty further predicted HIV testing, while recent drug use reduced the odds of past-year HIV testing. Among men, past-year HIV testing was also associated with lifetime incarceration and substance use treatment. CONCLUSION: The present study identified gaps in rates of HIV testing among heterosexuals at high risk for HIV, and both common and gender-specific facilitators of HIV testing. Findings suggest a number of avenues for increasing HIV testing rates, including increasing the number and types of settings offering high-quality HIV testing; promoting STI as well as HIV testing; better integrating STI and HIV testing systems; implementing peer-driven social/behavioral intervention approaches to harness the positive influence of social networks and reduce unfavorable shared peer norms; and specialized approaches for women who use drugs. PMID- 27200331 TI - Seasonal Variation in Skin Cancer Diagnosis. AB - PURPOSE: Seasonality of skin cancer is well known, and it is influenced by a number of variables, such as exposure and personal characteristics, but also health service factors. We investigated the variations in the diagnosis melanoma skin cancer (MSC) and non-melanoma skin cancer (NMSC) during the year. METHODS: We analyzed incident cases recorded in the Umbria Regional Cancer registry from 1994 to 2010 (1745 cases of MSC, 50% females, and 15,992 NMSC, 41% females). The Walter-Elwood test was used to assess seasonal effects. Relative risks were analyzed using negative binomial regression and splines. RESULTS: Seasonality of MSC and NMSC was similar. Incidence peaks were observed in weeks 8, 24, and 43 (February, July, and October) and troughs in weeks 16, 32, 52, and 1 (August and December). Both NMSC and MSC cancers showed most elevated risks in autumn. A seasonal effect was present for trunk (p < 0.001) and absent for face cancers (p = 0.3). CONCLUSION: The observed pattern of diagnoses presumably depends on health service factors (e.g., organization of melanoma days, reduced access to care in August and during Christmas holidays) and personal factors (e.g., unclothing in the summer and delays in seeking care). High incidence rates in autumn could also in part depend on a late cancer progression effect of UV exposure. More efforts should be placed in order to guarantee uniform access to care through the year. PMID- 27200332 TI - Development of Occupational Health Measures for the National Health Security Preparedness Index. PMID- 27200333 TI - Mirror, Mirror by the Stairs: The Impact of Mirror Exposure on Stair versus Elevator Use in College Students. AB - Previous research has indicated that self-awareness-inducing mirrors can successfully incite behaviors that align with one's personal values, such as helping others. Other research has found a large discrepancy between the high percentage of young adults who report valuing the healthfulness of physical activity (PA) and the low percentage who actually meet PA participation standards. However, few studies have examined how mirror exposure and both perceived and actual body size influence highly valued PA participation among college students. The present study assessed stair versus elevator use on a western college campus and hypothesized that mirror exposure would increase the more personally healthy transportation method of stair use. In accordance with previous research, it was also hypothesized that males and those with a lower body mass index (BMI) would be more likely to take the stairs, and that body size distorting mirrors would impact the stair-elevator decision. One hundred sixty seven students (51% male) enrolled in an introductory psychology course were recruited to take a survey about their "transportation choices" at an indoor campus parking garage. Participants were individually exposed to either no mirror, a standard full-length mirror, or a full-length mirror manipulated to make the reflected body size appear either slightly thinner or slightly wider than normal before being asked to go to the fourth floor of the garage for a survey. Participants' choice of floor-climbing method (stairs or elevator) was recorded, and they were administered an Internet-based survey assessing demographic information, BMI, self-awareness, perceived body size, and other variables likely to be associated with stair use. Results from logistic regression analyses revealed that participants who were not exposed to a mirror [odds ratios (OR) = 0.37, 95% CI: 0.14-0.96], males (OR = 0.33, 95% CI: 0.13 0.85), those with lower BMI (OR = 0.84, 95% CI: 0.71-0.99), those with higher exercise participation (OR = 1.09, 95% CI: 1.02-1.18), and those engaging in more unhealthy weight-control behaviors (OR = 1.55, 95% CI: 1.14-2.11) showed increased odds of taking the stairs. Implications and future directions are discussed. PMID- 27200334 TI - Diet and Common Mental Disorders: The Imperative to Translate Evidence into Action. PMID- 27200336 TI - Perceptions of the Role of West Virginia's Cooperative Extension Service in Tobacco Control Coalitions. AB - Despite the fact that the consequences of tobacco use are well identified and known, it remains the single most preventable cause of disease and death in the United States. In West Virginia alone, the adult prevalence of cigarette smoking is 26.8%. This study researches the perceptions of the Cooperative Extension Service's involvement and role in county-level coalitions that address tobacco use in West Virginia. The research findings provide practical areas to increase the role of the Extension Service in these vital efforts to save lives, reduce economic hardships on families, and reduce the health-care burden on the state government. PMID- 27200335 TI - Depressive Symptoms Are Associated with More Hopelessness among White than Black Older Adults. AB - BACKGROUND: Hopelessness is a core component of depression. Our information is, however, very limited on ethnic variations in the magnitude of the link between depression and hopelessness. Using a national sample of older adults in United States, we compared Blacks and Whites for the magnitude of the association between depressive symptoms and hopelessness. METHODS: With a cross-sectional design, we used baseline data of the Religion, Aging, and Health Survey, 2001. Linear regression models were used for data analysis. Depressive symptoms (CES-D) and hopelessness were conceptualized as independent and dependent variables in different models, respectively. Demographic factors (age and gender), socioeconomic status (education and marital status), and health (self-rated health) were covariates. Ethnicity was the moderator. RESULTS: In the pooled sample, higher depressive symptoms were predictive of hopelessness, above and beyond all covariates. We also found significant interactions suggesting that the association between depressive symptoms and hopelessness is weaker among Blacks compared to Whites. In ethnic-specific models, there were significant associations between depressive symptoms and hopelessness among Whites but not Blacks. CONCLUSION: Depressive symptoms accompany more hopelessness among Whites than Blacks. This finding may explain why Blacks with depression have a lower tendency to commit suicide. Future research should test whether or not Whites with depression better respond to psychotherapies and cognitive behavioral therapies that focus on hope enhancement. This finding may explain differential correlates of depression based on race and ethnicity. PMID- 27200337 TI - Interactive Dissemination: Engaging Stakeholders in the Use of Aggregated Quality Improvement Data for System-Wide Change in Australian Indigenous Primary Health Care. AB - BACKGROUND: Integrating theory when developing complex quality improvement interventions can help to explain clinical and organizational behavior, inform strategy selection, and understand effects. This paper describes a theory informed interactive dissemination strategy. Using aggregated quality improvement data, the strategy seeks to engage stakeholders in wide-scale data interpretation and knowledge sharing focused on achieving wide-scale improvement in primary health-care quality. METHODS: An iterative process involving diverse stakeholders in Australian Aboriginal and Torres Strait Islander health-care delivery uses aggregated audit data collected across key areas of care. Phases of reporting and online feedback are used to identify: (1) priority areas for improvement; (2) health center, system, and staff attributes that may be important in addressing the identified priority evidence-practice gaps; and (3) strategies that could be introduced or strengthened to enable improvement. A developmental evaluation is being used to refine engagement processes and reports as the project progresses. DISCUSSION: This innovative dissemination approach is being used to encourage wide-scale interpretation and use of service performance data by policy-makers, managers, and other stakeholders, and to document knowledge about how to address barriers to achieving change. Through the developmental evaluation, the project provides opportunities to learn about stakeholders' needs in relation to the way data and findings are described and distributed, and elements of the dissemination strategy and report design that impact on the useability and uptake of findings. CONCLUSION: The project can contribute to knowledge about how to facilitate interactive wide-scale dissemination and about using data to co produce knowledge to improve health-care quality. PMID- 27200338 TI - System-Level Action Required for Wide-Scale Improvement in Quality of Primary Health Care: Synthesis of Feedback from an Interactive Process to Promote Dissemination and Use of Aggregated Quality of Care Data. AB - INTRODUCTION: There is an enduring gap between recommended practice and care that is actually delivered; and there is wide variation between primary health care (PHC) centers in delivery of care. Where aspects of care are not being done well across a range of PHC centers, this is likely due to inadequacies in the broader system. This paper aims to describe stakeholders' perceptions of the barriers and enablers to addressing gaps in Australian Aboriginal and Torres Strait Islander chronic illness care and child health, and to identify key drivers for improvement. METHODS: This paper draws on data collected as part of a large-scale continuous quality improvement project in Australian Indigenous PHC settings. We undertook a qualitative assessment of stakeholder feedback on the main barriers and enablers to addressing gaps in care for Aboriginal and Torres Strait Islander children and in chronic illness care. Themes on barriers and enablers were further analyzed to develop a "driver diagram," an improvement tool used to locate barriers and enablers within causal pathways (as primary and secondary drivers), enabling them to be targeted by tailored interventions. RESULTS: We identified 5 primary drivers and 11 secondary drivers of high-quality care, and associated strategies that have potential for wide-scale implementation to address barriers and enablers for improving care. Perceived barriers to addressing gaps in care included both health system and staff attributes. Primary drivers were: staff capability to deliver high-quality care; availability and use of clinical information systems and decision support tools; embedding of quality improvement processes and data-driven decision-making; appropriate and effective recruitment and retention of staff; and community capacity, engagement and mobilization for health. Suggested strategies included mechanisms for increasing clinical supervision and support, staff retention, reorientation of service delivery, use of information systems and community health literacy. CONCLUSION: The findings identify areas of focus for development of barrier-driven, tailored interventions to improve health outcomes. They reinforce the importance of system level action to improve health center performance and health outcomes, and of developing strategies to address system-wide challenges that can be adapted to local contexts. PMID- 27200339 TI - Transitioning toward Sustainable Development Goals: The Role of Household Environment in Influencing Child Health in Sub-Saharan Africa and South Asia Using Recent Demographic Health Surveys. AB - The Millennium Development Goals are now replaced by 17 sustainable development goals. The emphasis of old goals was on improving water, sanitation, and child mortality conditions in developing countries. The study explored the major question about the association between different household environment conditions with child survival and health in Sub-Saharan African and South Asian countries in the current scenario. This paper estimated the risk of death, morbidity, and undernutrition among children living in households with the improved sources of water, sanitation, and non-solid cooking fuel. Two sources of information are explored in this study. First, data from World Health Statistics (WHS)-2014 for all of the Sub-Saharan African and South Asian countries were used. Second, available standard Demographic and Health Survey (DHS) performed in the countries of Sub-Saharan Africa and South Asia after 2010 was included in the study. It resulted in the inclusion of 15 countries which were Bangladesh (2011), Congo Republic (2013-2014), Cote d'Ivoire (2011-2012), Ethiopia (2011), Gambia (2013), Mali (2012-2013), Mozambique (2011), Namibia (2013), Nepal (2011), Niger (2012), Nigeria (2013), Pakistan (2012-2013), Sierra Leone (2013), Uganda (2011), and Zambia (2013). The scatter plot diagram was plotted, and the curve was fitted using the WHS-2014. Cox regression and logistic regression were used to estimate adjusted risks (odds ratio) of child mortality and health outcomes using DHSs. The use of non-solid cooking fuel was very high in most of the Sub-Saharan African and South Asian countries. There was a positive correlation between improving access to safe drinking water and sanitation. The exponential curve fitted well with child mortality and household environmental indicators. The use of improved source of water and sanitation significantly related with the lower odds ratio of death, morbidity, and undernutrition among children aged 12-59 months. The risks were not significant for children aged less than 12 months. The study provides evidence that these environmental conditions hold importance for improving child health, especially in Sub-Saharan African countries. PMID- 27200341 TI - Base-Modified Nucleosides: Etheno Derivatives. AB - This review presents synthesis and chemistry of nucleoside analogs, possessing an additional fused, heterocyclic ring of the "etheno" type, such as 1,N(6) ethenoadenosine, 1,N(4)-ethenocytidine, 1,N(2)-ethenoguanosine, and other related derivatives. Formation of ethenonucleosides, in the presence of alpha halocarbonyl reagents and their mechanism, stability, and degradation, reactions of substitution and transglycosylation, as well as their application in the nucleoside synthesis, have been described. Some of the discussed compounds may be applied as chemotherapeutic agents in antiviral and anticancer treatment, acting as pro-nucleosides of already known, biologically active nucleoside analogs. PMID- 27200340 TI - Modified Nucleoside Triphosphates for In-vitro Selection Techniques. AB - The development of SELEX (Selective Enhancement of Ligands by Exponential Enrichment) provides a powerful tool for the search of functional oligonucleotides with the ability to bind ligands with high affinity and selectivity (aptamers) and for the discovery of nucleic acid sequences with diverse enzymatic activities (ribozymes and DNAzymes). This technique has been extensively applied to the selection of natural DNA or RNA molecules but, in order to improve chemical and structural diversity as well as for particular applications where further chemical or biological stability is necessary, the extension of this strategy to modified oligonucleotides is desirable. Taking into account these needs, this review intends to collect the research carried out during the past years, focusing mainly on the use of modified nucleotides in SELEX and the development of mutant enzymes for broadening nucleoside triphosphates acceptance. In addition, comments regarding the synthesis of modified nucleoside triphosphate will be briefly discussed. PMID- 27200342 TI - Design and Preliminary Evaluation of a Two DOFs Cable-Driven Ankle-Foot Prosthesis with Active Dorsiflexion-Plantarflexion and Inversion-Eversion. AB - This paper describes the design of an ankle-foot robotic prosthesis controllable in the sagittal and frontal planes. The prosthesis was designed to meet the mechanical characteristics of the human ankle including power, range of motion, and weight. To transfer the power from the motors and gearboxes to the ankle-foot mechanism, a Bowden cable system was used. The Bowden cable allows for optimal placement of the motors and gearboxes in order to improve gait biomechanics such as the metabolic energy cost and gait asymmetry during locomotion. Additionally, it allows flexibility in the customization of the device to amputees with different residual limb sizes. To control the prosthesis, impedance controllers in both sagittal and frontal planes were developed. The impedance controllers used torque feedback from strain gages installed on the foot. Preliminary evaluation was performed to verify the capability of the prosthesis to track the kinematics of the human ankle in two degrees of freedom (DOFs), the mechanical efficiency of the Bowden cable transmission, and the ability of the prosthesis to modulate the impedance of the ankle. Moreover, the system was characterized by describing the relationship between the stiffness of the impedance controllers to the actual stiffness of the ankle. Efficiency estimation showed 85.4% efficiency in the Bowden cable transmission. The prosthesis was capable of properly mimicking human ankle kinematics and changing its mechanical impedance in two DOFs in real time with a range of stiffness sufficient for normal human walking. In dorsiflexion-plantarflexion (DP), the stiffness ranged from 0 to 236 Nm/rad and in inversion-eversion (IE), the stiffness ranged from 1 to 33 Nm/rad. PMID- 27200343 TI - Effect of Magnesium as Substitute Material in Enzyme-Mediated Calcite Precipitation for Soil-Improvement Technique. AB - The optimization of enzyme-mediated calcite precipitation was evaluated as a soil improvement technique. In our previous works, purified urease was utilized to bio catalyze the hydrolysis of urea, which causes the supplied Ca(2+) to precipitate with [Formula: see text] as calcium carbonate. In the present work, magnesium chloride was newly added to the injecting solutions to delay the reaction rate and to enhance the amount of carbonate precipitation. Soil specimens were prepared in PVC cylinders and treated with concentration-controlled solutions composed of urea, urease, calcium, and magnesium chloride. The mechanical properties of the treated soil specimens were examined through unconfined compressive strength (UCS) tests. A precipitation ratio of the carbonate up to 90% of the maximum theoretical precipitation was achieved by adding a small amount of magnesium chloride. Adding magnesium chloride as a delaying agent was indeed found to reduce the reaction rate of the precipitation, which may increase the volume of the treated soil if used in real fields because of the slower precipitation rate and the resulting higher injectivity. A mineralogical analysis revealed that magnesium chloride decreases the crystal size of the precipitated materials and that another carbonate of aragonite is newly formed. Mechanical test results indicated that carbonate precipitates within the soils and brings about a significant improvement in strength. A maximum UCS of 0.6 MPa was obtained from the treated samples. PMID- 27200344 TI - Editorial: Engineering Synthetic Metabolons: From Metabolic Modeling to Rational Design of Biosynthetic Devices. PMID- 27200345 TI - Recent Updates on DTD (D-Tyr-tRNA(Tyr) Deacylase): An Enzyme Essential for Fidelity and Quality of Protein Synthesis. AB - During protein synthesis, there are several checkpoints in the cell to ensure that the information encoded within genetic material is decoded correctly. Charging of tRNA with its cognate amino acid is one of the important steps in protein synthesis and is carried out by aminoacyl-tRNA synthetase (aaRS) with great accuracy. However, due to presence of D-amino acids in the cell, sometimes aaRS charges tRNA with D-amino acids resulting in the hampering of protein translational process, which is lethal to the cell. Every species has some mechanism in order to prevent the formation of D-amino acid-tRNA complex, for instance DTD (D-Tyr-tRNA deacylase) is an enzyme responsible for the cleavage of ester bond formed between D-amino acid and tRNA leading to error free translation process. In this review, structure, function, and enzymatic mechanism of DTD are discussed. The role of DTD as a drug target is also considered. PMID- 27200347 TI - Fibroblast Growth Factor 8 Expression in GT1-7 GnRH-Secreting Neurons Is Androgen Independent, but Can Be Upregulated by the Inhibition of DNA Methyltransferases. AB - Fibroblast growth factor 8 (FGF8) is a potent morphogen that regulates the embryonic development of hypothalamic neuroendocrine cells. Indeed, using Fgf8 hypomorphic mice, we showed that reduced Fgf8 mRNA expression completely eliminated the presence of gonadotropin-releasing hormone (GnRH) neurons. These findings suggest that FGF8 signaling is required during the embryonic development of mouse GnRH neurons. Additionally, in situ hybridization studies showed that the embryonic primordial birth place of GnRH neurons, the olfactory placode, is highly enriched for Fgf8 mRNA expression. Taken together these data underscore the importance of FGF8 signaling for GnRH emergence. However, an important question remains unanswered: How is Fgf8 gene expression regulated in the developing embryonic mouse brain? One major candidate is the androgen receptor (AR), which has been shown to upregulate Fgf8 mRNA in 60-70% of newly diagnosed prostate cancers. Therefore, we hypothesized that ARs may be involved in the regulation of Fgf8 transcription in the developing mouse brain. To test this hypothesis, we used chromatin-immunoprecipitation (ChIP) assays to elucidate whether ARs interact with the 5'UTR region upstream of the translational start site of the Fgf8 gene in immortalized mouse GnRH neurons (GT1-7) and nasal explants. Our data showed that while AR interacts with the Fgf8 promoter region, this interaction was androgen-independent, and that androgen treatment did not affect Fgf8 mRNA levels, indicating that androgen signaling does not induce Fgf8 transcription. In contrast, inhibition of DNA methyltransferases (DNMT) significantly upregulated Fgf8 mRNA levels indicating that Fgf8 transcriptional activity may be dependent on DNA methylation status. PMID- 27200346 TI - The Complexity of the ERK/MAP-Kinase Pathway and the Treatment of Melanoma Skin Cancer. AB - The central role played by the ERK/MAPK pathway downstream of RAS in human neoplasias is best exemplified in the context of melanoma skin cancer. Signaling through the MAPK pathway is crucial for the proliferation of melanocytes, the healthy pigment cells that give rise to melanoma. However, hyper-activation of the MAPK-pathway is found in over 90% of melanomas with approximately 50% of all patients displaying mutations in the kinase BRAF, and approximately 28% of all patients harboring mutations in the MAPK-pathway up-stream regulator NRAS. This finding has led to the development of BRAF and MEK inhibitors whose application in the clinic has shown unprecedented survival responses. Unfortunately the responses to MAPK pathway inhibitors are transient with most patients progressing within a year and a median progression free survival of 7-10 months. The disease progression is due to the development of drug-resistance based on various mechanisms, many of them involving a rewiring of the MAPK pathway. In this article we will review the complexity of MAPK signaling in melanocytic cells as well as the mechanisms of action of different MAPK-pathway inhibitors and their correlation with clinical response. We will reflect on mechanisms of innate and acquired resistance that limit patient's response, with a focus on the MAPK signaling network. Because of the resurgence of antibody-based immune-therapies there is a growing feeling of failure in the targeted therapy camp. However, recent studies have revealed new windows of therapeutic opportunity for melanoma sufferers treated with drugs targeting the MAPK pathway, and these opportunities will be discussed. PMID- 27200348 TI - The Molecular Architecture of Cell Adhesion: Dynamic Remodeling Revealed by Videonanoscopy. AB - The plasma membrane delimits the cell, which is the basic unit of living organisms, and is also a privileged site for cell communication with the environment. Cell adhesion can occur through cell-cell and cell-matrix contacts. Adhesion proteins such as integrins and cadherins also constitute receptors for inside-out and outside-in signaling within proteolipidic platforms. Adhesion molecule targeting and stabilization relies on specific features such as preferential segregation by the sub-membrane cytoskeleton meshwork and within membrane proteolipidic microdomains. This review presents an overview of the recent insights brought by the latest developments in microscopy, to unravel the molecular remodeling occurring at cell contacts. The dynamic aspect of cell adhesion was recently highlighted by super-resolution videomicroscopy, also named videonanoscopy. By circumventing the diffraction limit of light, nanoscopy has allowed the monitoring of molecular localization and behavior at the single molecule level, on fixed and living cells. Accessing molecular-resolution details such as quantitatively monitoring components entering and leaving cell contacts by lateral diffusion and reversible association has revealed an unexpected plasticity. Adhesion structures can be highly specialized, such as focal adhesion in motile cells, as well as immune and neuronal synapses. Spatiotemporal reorganization of adhesion molecules, receptors, and adaptors directly relates to structure/function modulation. Assembly of these supramolecular complexes is continuously balanced by dynamic events, remodeling adhesions on various timescales, notably by molecular conformation switches, lateral diffusion within the membrane and endo/exocytosis. Pathological alterations in cell adhesion are involved in cancer evolution, through cancer stem cell interaction with stromal niches, growth, extravasation, and metastasis. PMID- 27200349 TI - Protein Kinase D1 Signaling in Angiogenic Gene Expression and VEGF-Mediated Angiogenesis. AB - Protein kinase D 1 (PKD-1) is a signaling kinase important in fundamental cell functions including migration, proliferation, and differentiation. PKD-1 is also a key regulator of gene expression and angiogenesis that is essential for cardiovascular development and tumor progression. Further understanding molecular aspects of PKD-1 signaling in the regulation of angiogenesis may have translational implications in obesity, cardiovascular disease, and cancer. The author will summarize and provide the insights into molecular mechanisms by which PKD-1 regulates transcriptional expression of angiogenic genes, focusing on the transcriptional regulation of CD36 by PKD-1-FoxO1 signaling axis along with the potential implications of this axis in arterial differentiation and morphogenesis. He will also discuss a new concept of dynamic balance between proangiogenic and antiangiogenic signaling in determining angiogenic switch, and stress how PKD-1 signaling regulates VEGF signaling-mediated angiogenesis. PMID- 27200350 TI - CNS Remyelination and the Innate Immune System. AB - A misguided inflammatory response is frequently implicated in myelin damage. Particularly prominent among myelin diseases, multiple sclerosis (MS) is an autoimmune condition, with immune-mediated damage central to its etiology. Nevertheless, a robust inflammatory response is also essential for the efficient regeneration of myelin sheaths after such injury. Here, we discuss the functions of inflammation that promote remyelination, and how these have been experimentally disentangled from the pathological facets of the immune response. We focus on the contributions that resident microglia and monocyte-derived macrophages make to remyelination and compare the roles of these two populations of innate immune cells. Finally, the current literature is framed in the context of developing therapies that manipulate the innate immune response to promote remyelination in clinical myelin disease. PMID- 27200354 TI - Response: "Commentary: Peripartum Cardiomyopathy in Intensive Care Unit: An Update". PMID- 27200352 TI - A Prospective Randomized Study on the Risk of Bacteremia in Banding versus Sclerotherapy of Esophageal Varices. AB - BACKGROUND: Esophageal variceal banding may be less likely to cause bacteremia than sclerotherapy. The existing data about the frequency of bacteremia after esophageal variceal banding are conflicting, and few studies include both banding and sclerotherapy. AIMS: We conducted a prospective randomized controlled trial to compare the frequency of bacteremia after esophageal variceal banding and sclerotherapy. METHODS: Over a 2-year period, patients with liver disease admitted for upper gastrointestinal bleeding or for outpatient elective variceal therapy were enrolled. New patients were randomized preprocedure to either banding or sclerotherapy, and subsequent sessions utilized the initial procedure. The groups consisted of banding, sclerotherapy, and endoscopy without variceal therapy. Subjects underwent endoscopy by one out of three gastroenterologists. Blood cultures were obtained 5 min before and 30 min after endoscopy to check for bacteremia. RESULTS: Postendoscopic blood cultures were positive following 4 out of 139 (2.9%) sessions: 1 sclerotherapy and 3 control sessions. All postendoscopic positive blood cultures were found following emergency sessions (4/92, 4.3%). One pre-endoscopic blood culture was positive in a patient with emergency banding. The rates of positive postendoscopic blood cultures among groups with emergency banding (0/22, 0%), emergency sclerotherapy (1/41, 2.3%), and emergency control (3/29, 10.3%) were not significantly different. Postendoscopic positive blood cultures were not found after elective sessions with either banding or sclerotherapy. CONCLUSIONS: Postendoscopic bacteremia was infrequent following emergency endoscopy in patients with esophageal variceal bleeding. Bacteremia was not found after esophageal variceal banding, although this was not significantly less frequent than after sclerotherapy. Postendoscopic bacteremia was not associated with elective variceal therapy. PMID- 27200353 TI - A Cross-sectional Study of KLKB1 and PRCP Polymorphisms in Patient Samples with Cardiovascular Disease. AB - Plasma kallikrein formed from prekallikrein (PK) produces bradykinin from kininogens and activates factor XII. Plasma PK is activated by factors alphaXIIa, betaXIIa, or prolylcarboxypeptidase (PRCP). A cross-sectional investigation determined if there is an association of PRCP and KLKB1 polymorphisms with cardiovascular disease (CVD). DNA was obtained from 2243 individuals from the Prevention of Events with Angiotensin Converting Enzyme trial. Two PRCP SNPs, rs7104980 and rs2298668, and two KLKB1 SNPs, rs3733402 and rs3087505, were genotyped. Logistic regression models were performed for history of diabetes, myocardial infarction, stroke, angina, angiographic coronary disease, CABG, intermittent claudication, percutaneous transluminal coronary angioplasty (PTCA), and transient ischemic attack. The PRCP SNP rs7104980 increased the odds of having a history of PTCA by 21% [odds ratio (OR) = 1.211; 95% confidence intervals (CI) = (1.008, 1.454)]; P = 0.041, but was non-significant after Bonferroni correction. Alternatively, having the G allele for rs3733402 (KLKB1 gene) decreased the odds of having a history of angiographic coronary disease by 24% [OR = 0.759; 95% CI = (0.622, 0.927)]; P = 0.007 that was statistically significant (P < 0.01) after Bonferroni correction for multiple hypothesis testing. When the best-fit model based on the Akaike information criterion controlled for age, weight, gender, hypertension, and history of angina, the G allele of KLKB1 rs3733402 that is associated with less plasma kallikrein activity correlated with reduced history of CVD. PMID- 27200355 TI - Laparoscopic Common Bile Duct Exploration: 9 Years Experience from a Single Center. AB - INTRODUCTION: The aim of the study was to evaluate the safety and feasibility of laparoscopic common bile duct exploration (LCBDE) through cholangiotomy with T tube placement in one seance for common bile duct stones (CBDS). METHODS: Between January 2005 and December 2010, a total of 99 patients with CBDS stones undergoing LCBDE with T-tube insertion at Enkoping Hospital, Sweden, were registered prospectively. All patients were followed up by review of the patient records according to a standardized protocol. RESULTS: No severe intraoperative complications were registered. Four procedures required conversion to open cholecystectomy due to impacted stones or technical difficulty. The mean operative time was 194 min [(SD) 57 min]. The mean postoperative hospital stay was 4.8 days, SD 2.4 days. At secondary cholangiography, 2 (2%) retained stones were found. Two (2%) patients had minor bile leakage, which resolved spontaneously. None of the patients experienced biliary peritonitis, biliary fistula, pancreatitis, or cholangitis. No death within 30 days after surgery was seen. No patient was readmitted with clinical signs of stricture. CONCLUSION: If performed by a surgeon familiar with the technique, LCBDE is a safe and feasible alternative for managing CBDS. The advantages are most pronounced in the case of multiple and large CBDS. The risk for retained stones and stricture is low. PMID- 27200356 TI - Expression of the Components of the Renin-Angiotensin System in Venous Malformation. AB - BACKGROUND: Venous malformation (VM) is the most common form of vascular malformation, consisting of a network of thin-walled ectatic venous channels with deficient or absent media. This study investigated the expression of the components of the renin-angiotensin system (RAS), namely, (pro)renin receptor (PRR), angiotensin-converting enzyme (ACE), angiotensin II receptor 1 (ATIIR1), and angiotensin II receptor 2 (AIITR2) in subcutaneous (SC) and intramuscular (IM) VM. MATERIALS AND METHODS: SC (n = 7) and IM (n = 7) VM were analyzed for the expression of PRR, ACE, ATIIR1, and ATIIR2 using 3,3-diaminobenzidine and immunofluorescent (IF) immunohistochemical (IHC) staining and NanoString gene expression analysis. RESULTS: IHC staining showed expression of PRR, ACE, and ATIIR1, and faint expression of ATIIR2 in the endothelium of SC and IM VM. Furthermore, ATIIR2 was expressed by cells away from the endothelium in both SC and IM VM lesions examined. NanoString analysis demonstrated the presence of PRR, ACE, and ATIIR1 but not ATIIR2. CONCLUSION: The presence of PRR, ACE, ATIIR1, and potentially ATIIR2, in both SC and IM VM, suggests a role for the RAS in the biology of VM. This novel finding may lead to a mechanism-based therapy for VM. PMID- 27200351 TI - p38 MAPK Signaling in Osteoblast Differentiation. AB - The skeleton is a highly dynamic tissue whose structure relies on the balance between bone deposition and resorption. This equilibrium, which depends on osteoblast and osteoclast functions, is controlled by multiple factors that can be modulated post-translationally. Some of the modulators are Mitogen-activated kinases (MAPKs), whose role has been studied in vivo and in vitro. p38-MAPK modifies the transactivation ability of some key transcription factors in chondrocytes, osteoblasts and osteoclasts, which affects their differentiation and function. Several commercially available inhibitors have helped to determine p38 action on these processes. Although it is frequently mentioned in the literature, this chemical approach is not always as accurate as it should be. Conditional knockouts are a useful genetic tool that could unravel the role of p38 in shaping the skeleton. In this review, we will summarize the state of the art on p38 activity during osteoblast differentiation and function, and emphasize the triggers of this MAPK. PMID- 27200357 TI - Delayed Gastric Emptying after Pancreatic Surgery: Analysis of Factors Determinant for the Short-term Outcome. AB - BACKGROUND: Delayed gastric emptying (DGE) frequently complicates pancreatoduodenectomy (PD). Mainly DGE develops as consequence of postoperative intra-abdominal complications (secondary), while the incidence of primary DGE (i.e., not related to surgical complications) has rarely been studied. Moreover, the pathogenesis of DGE is complex and needs to be further elucidated. The present study aimed at highlighting potential mechanisms behind primary and above all secondary DGE by studying a variety of different pancreatic surgical procedures. PATIENTS AND METHODS: During the time period 2008-2011, 327 patients underwent pancreatic resective procedures at Karolinska University Hospital. Of these, 242 were PD and 56 tail resections, 17 had a duodenal preserving pancreatectomy for chronic pancreatitis, and 15 patients with familial duodenal polyposis had a pancreas preserving duodenectomy. All postoperative courses were assessed and scored according to Clavien-Dindo. The presence of DGE was evaluated and recorded according to the definition launched by the International Study Group for Pancreatic Surgery (ISGPS). Crude associations were studied in a univariate model, followed by a multivariate analysis of the respective factors. The associations were presented as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: In total DGE emerged during the postoperative course in about 40% of the PD cases. About half of those (n = 47) were scored as being primary. The majority of the primary DGEs were classified as A (n = 26) and only four as grade C, whereas among the secondary cases significantly more patients were scored as grade C (p < 0.01). In those submitted to a pancreatic body and tail resection 25% reported DGE. The distribution of the different grades of DGE in patients with a tail resection followed the same pattern with a predominance of Grade A cases with an equal distribution between those being scored as primary and secondary. Duodenal preservation, as well as keeping the pancreas intact following duodenectomy, was not followed by primary DGE. Multivariate risk factor analyses for the development of primary GE revealed no specific risk profile except for high age. CONCLUSION: DGE is frequently seen after different surgical procedures directed toward the pancreatic gland. DGE is most commonly seen after PD, and half of these cases are scored as primary DGE. Primary and secondary DGE are seen in one-quarter of the cases even after pancreatic tail resection emphasizing the complex nature of the pathogenesis. Resection of the duodenum as an important mechanism behind DGE is not supported by the present results. PMID- 27200358 TI - Robotic Surgery in Gynecology. AB - Minimally invasive surgery (MIS) can be considered as the greatest surgical innovation over the past 30 years. It revolutionized surgical practice with well proven advantages over traditional open surgery: reduced surgical trauma and incision-related complications, such as surgical-site infections, postoperative pain and hernia, reduced hospital stay, and improved cosmetic outcome. Nonetheless, proficiency in MIS can be technically challenging as conventional laparoscopy is associated with several limitations as the two-dimensional (2D) monitor reduction in-depth perception, camera instability, limited range of motion, and steep learning curves. The surgeon has a low force feedback, which allows simple gestures, respect for tissues, and more effective treatment of complications. Since the 1980s, several computer sciences and robotics projects have been set up to overcome the difficulties encountered with conventional laparoscopy, to augment the surgeon's skills, achieve accuracy and high precision during complex surgery, and facilitate widespread of MIS. Surgical instruments are guided by haptic interfaces that replicate and filter hand movements. Robotically assisted technology offers advantages that include improved three dimensional stereoscopic vision, wristed instruments that improve dexterity, and tremor canceling software that improves surgical precision. PMID- 27200359 TI - The Role of the Membrane-Initiated Heat Shock Response in Cancer. AB - The heat shock response (HSR) is a cellular response to diverse environmental and physiological stressors resulting in the induction of genes encoding molecular chaperones, proteases, and other proteins that are essential for protection and recovery from cellular damage. Since different perturbations cause accumulation of misfolded proteins, cells frequently encounter fluctuations in the environment which alter proteostasis. Since tumor cells use their natural adaptive mechanism of coping with stress and misfolded proteins, in recent years, the proteostasis network became a promising target for anti-tumor therapy. The membrane is the first to be affected by heat shock and therefore may be the first one to sense heat shock. The membrane also connects between the extracellular and the intracellular signals. Hence, there is a "cross talk" between the HSR and the membranes since heat shock can induce changes in the fluidity of membranes, leading to membrane lipid remodeling that occurs in several diseases such as cancer. During the last decade, a new possible therapy has emerged in which an external molecule is used that could induce membrane lipid re-organization. Since at the moment there are very few substances that regulate the HSR effectively, an alternative way has been searched to modulate chaperone activities through the plasma membrane. Recently, we suggested that the use of the membrane Transient Receptor Potential Vanilloid-1 (TRPV1) modulators regulated the HSR in cancer cells. However, the primary targets of the signal transduction pathway are yet un known. This review provides an overview of the current literature regarding the role of HSR in membrane remodeling in cancer since a deep understanding of the membrane biology in cancer and the membrane heat sensing pathway is essential to design novel efficient therapies. PMID- 27200360 TI - Editorial: Optogenetic Tools in the Molecular Spotlight. PMID- 27200361 TI - Mathematical Modeling and Dynamic Simulation of Metabolic Reaction Systems Using Metabolome Time Series Data. AB - The high-throughput acquisition of metabolome data is greatly anticipated for the complete understanding of cellular metabolism in living organisms. A variety of analytical technologies have been developed to acquire large-scale metabolic profiles under different biological or environmental conditions. Time series data are useful for predicting the most likely metabolic pathways because they provide important information regarding the accumulation of metabolites, which implies causal relationships in the metabolic reaction network. Considerable effort has been undertaken to utilize these data for constructing a mathematical model merging system properties and quantitatively characterizing a whole metabolic system in toto. However, there are technical difficulties between benchmarking the provision and utilization of data. Although, hundreds of metabolites can be measured, which provide information on the metabolic reaction system, simultaneous measurement of thousands of metabolites is still challenging. In addition, it is nontrivial to logically predict the dynamic behaviors of unmeasurable metabolite concentrations without sufficient information on the metabolic reaction network. Yet, consolidating the advantages of advancements in both metabolomics and mathematical modeling remain to be accomplished. This review outlines the conceptual basis of and recent advances in technologies in both the research fields. It also highlights the potential for constructing a large-scale mathematical model by estimating model parameters from time series metabolome data in order to comprehensively understand metabolism at the systems level. PMID- 27200362 TI - A Functional oriT in the Ptw Plasmid of Burkholderia cenocepacia Can Be Recognized by the R388 Relaxase TrwC. AB - Burkholderia cenocepacia is both a plant pathogen and the cause of serious opportunistic infections, particularly in cystic fibrosis patients. B. cenocepacia K56-2 harbors a native plasmid named Ptw for its involvement in the Plant Tissue Watersoaking phenotype. Ptw has also been reported to be important for survival in human cells. Interestingly, the presence of PtwC, a homolog of the conjugative relaxase TrwC of plasmid R388, suggests a possible function for Ptw in conjugative DNA transfer. The ptw region includes Type IV Secretion System genes related to those of the F plasmid. However, genes in the adjacent region shared stronger homology with the R388 genes involved in conjugative DNA metabolism. This region included the putative relaxase ptwC, a putative coupling protein and accessory nicking protein, and a DNA segment with high number of inverted repeats and elevated AT content, suggesting a possible oriT. Although we were unable to detect conjugative transfer of the Ptw resident plasmid, we detected conjugal mobilization of a co-resident plasmid containing the ptw region homologous to R388, demonstrating the cloned ptw region contains an oriT. A similar plasmid lacking ptwC could not be mobilized, suggesting that the putative relaxase PtwC must act in cis on its oriT. Remarkably, we also detected mobilization of a plasmid containing the Ptw oriT by the R388 relaxase TrwC, yet we could not detect PtwC-mediated mobilization of an R388 oriT-containing plasmid. Our data unambiguously show that the Ptw plasmid harbors DNA transfer functions, and suggests the Ptw plasmid may play a dual role in horizontal DNA transfer and eukaryotic infection. PMID- 27200364 TI - Seroprevalence of Foot-and-Mouth Disease in Susceptible Wildlife in Israel. AB - Foot-and-mouth disease (FMD) epidemics recur in Israel almost every year. Wild even-toed ungulates are seldom affected during these epidemics. The seroprevalence of FMD in wild ungulates during 2000 and 2005-2013 was estimated using anti-non-structural proteins ELISA. Overall, 209 samples were tested, comprising sera of 120 wild boar (Sus scrofa lybicus), 64 mountain gazelles (Gazella gazella gazella), 6 water buffaloes (Bubalus bubalis), and 19 Persian fallow deer (Dama dama mesopotamica). None of the tested animals presented clinical signs of FMD during blood collection. Sixteen samples [7.7% (95% confidence interval (CI95%) = 4.4-12.1%)] were found to be seropositive. Fifteen out of 120 samples (12.5%) from wild boar were seropositive, compared with only 1 out of 89 samples (1.1%) from all other species combined (Fisher's exact test: p = 0.003). Most of the positive samples obtained from wild boar [13/15 (86.7%)] were collected during 2007, and analysis was restricted to that year and species only. The seroprevalence of FMD in this species during 2007 was estimated at 54.2% (CI95% = 32.8-74.5%; n = 24). A significant infection cluster, comprising nine seropositive samples collected in three different locations, was identified in the north-eastern part of Israel. These findings indicate that wild boar was affected during the 2007 FMD epidemic, even though wild boar presenting FMD typical clinical signs were not observed during that year. The actual role of wild boar in the spread of FMD virus in this epidemic, however, could not be determined. The negligible seroprevalence of FMD found for all other surveillance years indicates that ongoing circulation of FMD among wildlife in Israel is unlikely. It is concluded that while the role of wildlife species in the dynamics of FMD in Israel is usually limited, there might be occasions, in which wildlife plays a part in the spread of the virus. PMID- 27200363 TI - The Brugada Syndrome: A Rare Arrhythmia Disorder with Complex Inheritance. AB - For the last 10 years, applying new sequencing technologies to thousands of whole exomes has revealed the high variability of the human genome. Extreme caution should thus be taken to avoid misinterpretation when associating rare genetic variants to disease susceptibility. The Brugada syndrome (BrS) is a rare inherited arrhythmia disease associated with high risk of sudden cardiac death in the young adult. Familial inheritance has long been described as Mendelian, with autosomal dominant mode of transmission and incomplete penetrance. However, all except 1 of the 23 genes previously associated with the disease have been identified through a candidate gene approach. To date, only rare coding variants in the SCN5A gene have been significantly associated with the syndrome. However, the genotype/phenotype studies conducted in families with SCN5A mutations illustrate the complex mode of inheritance of BrS. This genetic complexity has recently been confirmed by the identification of common polymorphic alleles strongly associated with disease risk. The implication of both rare and common variants in BrS susceptibility implies that one should first define a proper genetic model for BrS predisposition prior to applying molecular diagnosis. Although long remains the way to personalized medicine against BrS, the high phenotype variability encountered in familial forms of the disease may partly find an explanation into this specific genetic architecture. PMID- 27200365 TI - Computed Tomographic Features in a Case of Bilateral Neoplastic Cryptorchidism with Suspected Torsion in a Dog. AB - An 11-year-old male German Shepherd dog presented for inappetence and weight loss. Physical examination and initial bloodwork revealed palpable abdominal masses, mild non-regenerative anemia, and thrombocytopenia. Survey radiography and abdominal ultrasonography confirmed the presence of bilateral abdominal masses and lymphadenopathy. Contrast-enhanced computed tomography (CT) was performed in order to further investigate the origin of the intraabdominal masses, confirming two enlarged cryptorchid testes, one of which had an associated CT "whirl sign." Histopathology of the testes and lymph nodes revealed bilateral malignant Sertoli cell tumors and seminomas with lymph node metastasis of both neoplasms. The purpose of this case report is to discuss the benefits of CT in the diagnosis of cryptorchid testes and describe an additional organ that may display CT "whirl sign." PMID- 27200366 TI - The Relationship between Older Adults' Risk for a Future Fall and Difficulty Performing Activities of Daily Living. AB - Functional status is often defined by cumulative scores across indices of independence in performing basic and instrumental activities of daily living (ADL/IADL), but little is known about the unique relationship of each daily activity item with the fall outcome. The purpose of this retrospective study was to examine the level of relative risk for a future fall associated with difficulty with performing various tasks of normal daily functioning among older adults who had fallen at least once in the past 12 months. The sample was comprised of community-dwelling individuals 70 years and older from the 1984-1990 Longitudinal Study of Aging by Kovar, Fitti, and Chyba (1992). Risk analysis was performed on individual items quantifying 6 ADLs and 7 IADLs, as well as 10 items related to mobility limitations. Within a subsample of 1,675 older adults with a history of at least one fall within the past year, the responses of individuals who reported multiple falls were compared to the responses of participants who had a single fall and reported 1) difficulty with walking and/or balance (FRAIL group, n = 413) vs. 2) no difficulty with walking or dizziness (NDW+ND group, n = 415). The items that had the strongest relationships and highest risk ratios for the FRAIL group (which had the highest probabilities for a future fall) included difficulty with: eating (73%); managing money (70%); biting or chewing food (66%); walking a quarter of a mile (65%); using fingers to grasp (65%); and dressing without help (65%). For the NDW+ND group, the most noteworthy items included difficulty with: bathing or showering (79%); managing money (77%); shopping for personal items (75%); walking up 10 steps without rest (72%); difficulty with walking a quarter of a mile (72%); and stooping/crouching/kneeling (70%). These findings suggest that individual items quantifying specific ADLs and IADLs have substantive relationships with the fall outcome among older adults who have difficulty with walking and balance, as well as among older individuals without dizziness or difficulty with walking. Furthermore, the examination of the relationships between items that are related to more challenging activities and the fall outcome revealed that higher functioning older adults who reported difficulty with the 6 items that yielded the highest risk ratios may also be at elevated risk for a fall. PMID- 27200367 TI - Pan-cancer analyses of the nuclear receptor superfamily. AB - Nuclear receptors (NR) act as an integrated conduit for environmental and hormonal signals to govern genomic responses, which relate to cell fate decisions. We review how their integrated actions with each other, shared co factors and other transcription factors are disrupted in cancer. Steroid hormone nuclear receptors are oncogenic drivers in breast and prostate cancer and blockade of signaling is a major therapeutic goal. By contrast to blockade of receptors, in other cancers enhanced receptor function is attractive, as illustrated initially with targeting of retinoic acid receptors in leukemia. In the post-genomic era large consortia, such as The Cancer Genome Atlas, have developed a remarkable volume of genomic data with which to examine multiple aspects of nuclear receptor status in a pan-cancer manner. Therefore to extend the review of NR function we have also undertaken bioinformatics analyses of NR expression in over 3000 tumors, spread across six different tumor types (bladder, breast, colon, head and neck, liver and prostate). Specifically, to ask how the NR expression was distorted (altered expression, mutation and CNV) we have applied bootstrapping approaches to simulate data for comparison, and also compared these NR findings to 12 other transcription factor families. Nuclear receptors were uniquely and uniformly downregulated across all six tumor types, more than predicted by chance. These approaches also revealed that each tumor type had a specific NR expression profile but these were most similar between breast and prostate cancer. Some NRs were down-regulated in at least five tumor types (e.g. NR3C2/MR and NR5A2/LRH-1)) whereas others were uniquely down regulated in one tumor (e.g. NR1B3/RARG). The downregulation was not driven by copy number variation or mutation and epigenetic mechanisms maybe responsible for the altered nuclear receptor expression. PMID- 27200368 TI - Genetic Variants of CD40 Gene Are Associated with Coronary Artery Disease and Blood Lipid Levels. AB - Objectives. The present study aimed to evaluate the effect of CD40 and CXCR4 genes polymorphisms on CAD susceptibility and the blood lipid levels and history of cardiovascular risk factors in a Chinese Han population. Materials and Methods. A total of 583 unrelated patients with CAD and 540 controls were recruited. Two tag SNPs (rs4239702 and rs1535045) at the CD40 locus and one tag SNP (rs2228014) at the CXCR4 locus were genotyped using the SEQUENOM Mass-ARRAY system. Results. After adjusting the risk factors, the frequency of rs1535045-T allele was also higher in patients than controls. Haplotype analysis showed that the rs4239702(C)-rs1535045(T) haplotype was associated with CAD. People with rs4239702-TT genotype had higher blood lipid levels in case group while it was not in the control group. History of cardiovascular risk factors showed no association for the three SNPs in case group and control group. Conclusions. rs1535045 in CD40 gene is likely to be associated with CAD in the Chinese Han population. rs4239702(C)-rs1535045(T) haplotype was associated with CAD. Only in CAD patients, the blood lipid level of patients with rs4239702-TT genotype was higher than other patients. CXCR4 gene may not relate to CAD. PMID- 27200370 TI - Improve the Anaerobic Biodegradability by Copretreatment of Thermal Alkali and Steam Explosion of Lignocellulosic Waste. AB - Effective alteration of the recalcitrance properties like crystallization of cellulose, lignin shield, and interlinking of lignocellulosic biomass is an ideal way to utilize the full-scale potential for biofuel production. This study exhibited three different pretreatment effects to enhance the digestibility of corn stover (CS) for methane production. In this context, steam explosion (SE) and thermal potassium hydroxide (KOH-60 degrees C) treated CS produced the maximal methane yield of 217.5 and 243.1 mL/gvs, which were 40.0% and 56.4% more than untreated CS (155.4 mL/gvs), respectively. Copretreatment of thermal potassium hydroxide and steam explosion (CPTPS) treated CS was highly significant among all treatments and improved 88.46% (292.9 mL/gvs) methane yield compared with untreated CS. Besides, CPTPS also achieved the highest biodegradability up to 68.90%. Three kinetic models very well simulated dynamics of methane production yield. Moreover, scanning electron microscopy (SEM), Fourier transform infrared (FTIR), and X-ray diffraction (XRD) analyses declared the most effective changes in physicochemical properties after CPTPS pretreatment. Thus, CPTPS might be a promising approach to deconstructing the recalcitrance of lignocellulosic structure to improve the biodegradability for AD. PMID- 27200369 TI - Roles and Clinical Applications of OPG and TRAIL as Biomarkers in Cardiovascular Disease. AB - Cardiovascular diseases (CVD) remain the major cause of death and premature disability in Western societies. Assessing the risk of CVD is an important aspect in clinical decision-making. Among the growing number of molecules that are studied for their potential utility as CVD biomarkers, a lot of attention has been focused on osteoprotegerin (OPG) and its ligands, which are receptor activator of nuclear factor kappaB ligand (RANKL) and TNF-related apoptosis inducing ligand. Based on the existing literature and on our experience in this field, here we review what the possible roles of OPG and TRAIL in CVD are and their potential utility as CVD biomarkers. PMID- 27200371 TI - Lycium barbarum Polysaccharide Mediated the Antidiabetic and Antinephritic Effects in Diet-Streptozotocin-Induced Diabetic Sprague Dawley Rats via Regulation of NF-kappaB. AB - Lycium barbarum, extensively utilized as a medicinal plant in China for years, exhibits antitumor, immunoregulative, hepatoprotective, and neuroprotective properties. The present study aims to investigate the hyperglycemic and antidiabetic nephritic effects of polysaccharide which is separated from Lycium barbarum (LBPS) in high-fat diet-streptozotocin- (STZ-) induced rat models. The reduced bodyweight and enhanced blood glucose concentration in serum were observed in diabetic rats, and they were significantly normalized to the healthy level by 100 mg/kg of metformin (Met) and LBPS at doses of 100, 250, and 500 mg/kg. LBPS inhibited albuminuria and blood urea nitrogen concentration and serum levels of inflammatory factors including IL-2, IL-6, TNF-alpha, IFN-alpha, MCP-1, and ICAM-1 compared with diabetic rats, and it indicates the protection on renal damage. Furthermore, the activities of SOD and GSH-Px in serum were enhanced strikingly by LBPS which suggests its antioxidation effects. LBPS, compared with nontreated diabetic rats, inhibited the expression of phosphor-nuclear factors kappa B (NF-kappaB) and inhibitor kappa B alpha in kidney tissues. Collectively, LBPS possesses antidiabetic and antinephritic effects related to NF-kappaB mediated antioxidant and antiinflammatory activities. PMID- 27200372 TI - Circulating Permeability Factors in Primary Focal Segmental Glomerulosclerosis: A Review of Proposed Candidates. AB - Primary focal segmental glomerulosclerosis (FSGS) is a major cause of the nephrotic syndrome and often leads to end-stage renal disease. This review focuses on circulating permeability factors in primary FSGS that have been implicated in the pathogenesis for a long time, partly due to the potential recurrence in renal allografts within hours after transplantation. Recently, three molecules have been proposed as a potential permeability factor by different groups: the soluble urokinase plasminogen activator receptor (suPAR), cardiotrophin-like cytokine factor-1 (CLCF-1), and CD40 antibodies. Both CLCF-1 and CD40 antibodies have not been validated by independent research groups yet. Since the identification of suPAR, different studies have questioned the validity of suPAR as a biomarker to distinguish primary FSGS from other proteinuric kidney diseases as well as suPAR's pathogenic role in podocyte damage. Researchers have suggested that cleaved molecules of suPAR have a pathogenic role in FSGS but further studies are needed to determine this role. In future studies, proposed standards for the research of the permeability factor should be carefully followed. The identification of the permeability factor in primary FSGS would be of great clinical relevance as it could influence potential individual treatment regimen. PMID- 27200373 TI - Conditional Granger Causality Analysis of Effective Connectivity during Motor Imagery and Motor Execution in Stroke Patients. AB - Aims. Motor imagery has emerged as a promising technique for the improvement of motor function following stroke, but the mechanism of functional network reorganization in patients during this process remains unclear. The aim of this study is to evaluate the cortical motor network patterns of effective connectivity in stroke patients. Methods. Ten stroke patients with right hand hemiplegia and ten normal control subjects were recruited. We applied conditional Granger causality analysis (CGCA) to explore and compare the functional connectivity between motor execution and motor imagery. Results. Compared with the normal controls, the patient group showed lower effective connectivity to the primary motor cortex (M1), the premotor cortex (PMC), and the supplementary motor area (SMA) in the damaged hemisphere but stronger effective connectivity to the ipsilesional PMC and M1 in the intact hemisphere during motor execution. There were tighter connections in the cortical motor network in the patients than in the controls during motor imagery, and the patients showed more effective connectivity in the intact hemisphere. Conclusions. The increase in effective connectivity suggests that motor imagery enhances core corticocortical interactions, promotes internal interaction in damaged hemispheres in stroke patients, and may facilitate recovery of motor function. PMID- 27200374 TI - Prevalence and Influencing Factors of Thyroid Dysfunction in HIV-Infected Patients. AB - Thyroid dysfunction is more common in human immunodeficiency virus (HIV) patients. But the effects of highly active antiretroviral therapy (HAART) and hepatitis B/C virus (HBV/HCV) coinfection on thyroid function is unclear. We retrospectively reviewed the data of 178 HIV patients and determined the prevalence of thyroid dysfunction and the relationship between thyroid hormone levels, CD4 cell count, HIV-1 duration, HAART duration/regimens, and HBV/HCV coinfection. Of the 178 patients, 59 (33.1%) had thyroid dysfunction, mostly hypothyroidism. Thyroid dysfunction was significantly more frequent in the HAART group (41/104, 39.4%) than in the HAART-naive group (18/74, 24.3%; P < 0.05). The mean CD4 cell count was significantly lower in patients with hypothyroidism (372 +/- 331/MUL) than in the other patients (P < 0.05). The FT4 level was significantly lower in the HAART group than in the HAART-naive group (1.09 +/- 0.23 versus 1.20 +/- 0.29 pg/mL, P < 0.05). FT3/FT4 levels were negatively related to HIV duration and FT3 levels were positively related to CD4 cell (P < 0.05). HBV patients had lower FT3 levels, while HCV patients had higher FT3 and FT4 levels (P < 0.05). Thyroid dysfunction is more common in HIV patients on HAART, mainly manifested as hypothyroidism. FT3/FT4 levels are correlated with HIV progression. HBV/HCV coinfection increases the probability of thyroid dysfunction. PMID- 27200375 TI - Lack of an Association between Neutrophil-to-Lymphocyte Ratio and PSA Failure of Prostate Cancer Patients Who Underwent Radical Prostatectomy. AB - Introduction. The neutrophil-to-lymphocyte ratio (NLR), which can be easily calculated from routine complete blood counts of the peripheral blood, has been suggested to serve as a prognostic factor for some solid malignancies. In the present study, we aimed to determine the relationship between NLR in prostate cancer patients undergoing radical prostatectomy (RP) and their prognosis. Materials and Methods. We assessed NLR in 73 men (patients) who received RP for their prostate cancer. We also performed immunohistochemistry for CD8 and CD66b in a separate set of RP specimens. Results. The median NLR in the 73 patients was 1.85. There were no significant correlations of NLR with tumor grade (p = 0.834), pathological T stage (p = 0.082), lymph node metastasis (p = 0.062), or resection margin status (p = 0.772). Based on the area under the receiver operator characteristic curve (AUROC) to predict biochemical recurrence after RP, potential NLR cut-off point was determined to be 2.88 or 3.88. However, both of these cut-off points did not precisely predict the prognosis. There were no statistically significant differences in the number of CD66b-positive neutrophils or CD8-positive lymphocytes between stromal tissues adjacent to cancer glands and stromal tissues away from cancer glands and between different grades or stages of tumors. Conclusions. There was no association between NLR and biochemical failure after prostatectomy. PMID- 27200377 TI - Tissue Engineering in Gene and Cell Therapies for Neurological Disorders. PMID- 27200378 TI - Association of Microalbuminuria with Metabolic Syndrome among Aged Population. AB - Background. The impact of the various components of metabolic syndrome (MetS) on chronic kidney disease has been conflicting. We aim to investigate the association between MetS and microalbuminuria and identify the major contributing components of MetS that result in microalbuminuria in the Chinese aged population. Methods. A total of 674 adults aged 55-98 years (males: 266; mean age: 66.5 +/- 7.5 years) were studied. MetS was defined by the 2004 Chinese Diabetes Society criteria and microalbuminuria by urine albumin-creatinine ratio (UACR) >=3 mg/mmoL. Results. The prevalence of microalbuminuria was gradually increased with increasing number of MetS components (P < 0.05). In multivariate regression, after adjusting for age and sex, MetS was the strongest correlate of microalbuminuria (OR = 1.781, 95% CI = 1.226-2.587; P < 0.05) followed by the fasting plasma glucose (FPG) (OR = 1.217, 95% CI = 1.044-1.092; P < 0.05), systolic blood pressure (SBP) (OR = 1.011, 95% CI = 1.107-1.338; P < 0.05), and high-density lipoprotein cholesterol (HDL-C) (OR = 0.576, 95% CI = 0.348-0.953; P < 0.05). Conclusions. MetS is independently associated with microalbuminuria in the Chinese aged population. Elevated FPG is the most predominant component of metabolic syndrome associated with microalbuminuria followed by elevated SBP and reduced HDL-C. PMID- 27200376 TI - The Effect of Autologous Platelet Lysate Eye Drops: An In Vivo Confocal Microscopy Study. AB - Purpose. To determine the effectiveness of autologous platelet lysate (APL) eye drops in patients with primary Sjogren syndrome (SS) dry eye, refractory to standard therapy, in comparison with patients treated with artificial tears. We focused on the effect of APL on cornea morphology with the in vivo confocal microscopy (IVCM). Methods. Patients were assigned to two groups: group A used autologous platelet lysate QID, and group B used preservative-free artificial tears QID, for 90 days. Ophthalmological assessments included ocular surface disease index (OSDI), best corrected visual acuity (BCVA), Schirmer test, fluorescein score, and breakup time (BUT). A subgroup of patients in group A underwent IVCM: corneal basal epithelium, subbasal nerves, Langerhans cells, anterior stroma activated keratocytes, and reflectivity were evaluated. Results. 60 eyes of 30 patients were enrolled; in group A (n = 20 patients) mean OSDI, fluorescein score, and BUT showed significant improvement compared with group B (n = 10 patients). The IVCM showed a significant increase in basal epithelium cells density and subbasal nerve plexus density and number and a decrease in Langerhans cells density (p < 0.05). Conclusion. APL was found effective in the treatment of SS dry eye. IVCM seems to be a useful tool to visualize cornea morphologic modifications. PMID- 27200380 TI - Immune Thrombocytopenia (ITP) Secondary to Subclinical Hashimoto's Thyroiditis: Role of Levothyroxine in Improving the Clinical Outcome of ITP. AB - Immune thrombocytopenia (ITP) is the most common cause of isolated thrombocytopenia in healthy people. ITP may rarely coexist with autoimmune thyroid disorders, which may indicate more complex defect in immune system. Primary ITP usually responds well to steroids and intravenous immunoglobulins. However, ITP may be difficult to treat when associated with thyroid autoimmune disorders. In such cases, treating the underlying thyroid disorder may significantly improve platelet count and can either cause remission of disease or improve response to standard ITP therapy. We report a case of 47-year-old male who was diagnosed with ITP and was also found to have subclinical Hashimoto's thyroiditis. Treatment of subclinical hypothyroidism with levothyroxine in our patient significantly improved the platelets, thus successfully bringing the disease in remission. PMID- 27200379 TI - Lower Hemoglobin Concentration Is Associated with Retinal Ischemia and the Severity of Diabetic Retinopathy in Type 2 Diabetes. AB - Aims. To assess the association of blood oxygen-transport capacity variables with the prevalence of diabetic retinopathy (DR), retinal ischemia, and macular oedema in patients with type 2 diabetes mellitus (T2DM). Methods. Cross-sectional, case control study (N = 312) with T2DM: 153 individuals with DR and 159 individuals with no DR. Participants were classified according to the severity of DR and the presence of retinal ischemia or macular oedema. Hematological variables were collected by standardized methods. Three logistic models were adjusted to ascertain the association between hematologic variables with the severity of DR and the presence of retinal ischemia or macular oedema. Results. Individuals with severe DR showed significantly lower hemoglobin, hematocrit, and erythrocyte levels compared with those with mild disease and in individuals with retinal ischemia and macular oedema compared with those without these disorders. Hemoglobin was the only factor that showed a significant inverse association with the severity of DR [beta-coefficient = -0.52, P value = 0.003] and retinal ischemia [beta-coefficient = -0.49, P value = 0.001]. Lower erythrocyte level showed a marginally significant association with macular oedema [beta-coefficient = -0.86, P value = 0.055]. Conclusions. In patients with DR, low blood oxygen transport capacity was associated with more severe DR and the presence of retinal ischemia. Low hemoglobin levels may have a key role in the development and progression of DR. PMID- 27200383 TI - Validated Measures of Publication Quality: Guide for Novice Researchers to Choose an Appropriate Journal for Paper Submission. PMID- 27200381 TI - Weathering a Cytokine Storm: A Case of EBV-Induced Hemophagocytic Lymphohistiocytosis. AB - Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening disease caused by excessive immune activation. Acquired HLH is seen in adults and is often caused by infection or malignancy. Diagnosis is difficult and usually missed as clinical and laboratory findings are nonspecific. Moreover, the pathophysiology of the systemic inflammatory response syndrome and/or sepsis is remarkably similar to HLH. Thus, in patients presenting with presumed severe sepsis or septic shock complicated by multiorgan failure without a clear infectious source, HLH should be considered. A disproportionately high ferritin may be one of the earlier laboratory findings to suggest HLH. We discuss a case of a young male who presented with presumed septic shock with multiorgan failure who was eventually found to have Epstein-Barr virus-induced HLH. PMID- 27200382 TI - Strategies to generate high-titer, high-potency recombinant AAV3 serotype vectors. AB - Although recombinant adeno-associated virus serotype 3 (AAV3) vectors were largely ignored previously, owing to their poor transduction efficiency in most cells and tissues examined, our initial observation of the selective tropism of AAV3 serotype vectors for human liver cancer cell lines and primary human hepatocytes has led to renewed interest in this serotype. AAV3 vectors and their variants have recently proven to be extremely efficient in targeting human and nonhuman primate hepatocytes in vitro as well as in vivo. In the present studies, we wished to evaluate the relative contributions of the cis-acting inverted terminal repeats (ITRs) from AAV3 (ITR3), as well as the trans-acting Rep proteins from AAV3 (Rep3) in the AAV3 vector production and transduction. To this end, we utilized two helper plasmids: pAAVr2c3, which carries rep2 and cap3 genes, and pAAVr3c3, which carries rep3 and cap3 genes. The combined use of AAV3 ITRs, AAV3 Rep proteins, and AAV3 capsids led to the production of recombinant vectors, AAV3-Rep3/ITR3, with up to approximately two to fourfold higher titers than AAV3-Rep2/ITR2 vectors produced using AAV2 ITRs, AAV2 Rep proteins, and AAV3 capsids. We also observed that the transduction efficiency of Rep3/ITR3 AAV3 vectors was approximately fourfold higher than that of Rep2/ITR2 AAV3 vectors in human hepatocellular carcinoma cell lines in vitro. The transduction efficiency of Rep3/ITR3 vectors was increased by ~10-fold, when AAV3 capsids containing mutations in two surface-exposed residues (serine 663 and threonine 492) were used to generate a S663V+T492V double-mutant AAV3 vector. The Rep3/ITR3 AAV3 vectors also transduced human liver tumors in vivo approximately twofold more efficiently than those generated with Rep2/ITR2. Our data suggest that the transduction efficiency of AAV3 vectors can be significantly improved both using homologous Rep proteins and ITRs as well as by capsid optimization. Thus, the combined use of homologous Rep proteins, ITRs, and capsids should also lead to more efficacious other AAV serotype vectors for their optimal use in human gene therapy. PMID- 27200384 TI - Posterolateral Corner of the Knee: Current Concepts. AB - Injuries to the posterolateral corner (PLC) comprise a significant portion of knee ligament injuries. A high index of suspicion is necessary when evaluating the injured knee to detect these sometimes occult injuries. Moreover, a thorough physical examination and a comprehensive review of radiographic studies are necessary to identify these injuries. In this sense, stress radiographs can help to objectively determine the extent of these lesions. Non-operative and operative treatment options have been reported depending on the extent of the injury. Complete PLC lesions rarely heal with non-operative treatment, and are therefore most often treated surgically. The purpose of this article was to review the anatomy and clinically relevant biomechanics, diagnosis algorithms, treatment and rehabilitation protocols for PLC injuries. PMID- 27200385 TI - Traumatic First Time Shoulder Dislocation: Surgery vs Non-Operative Treatment. AB - Management of first shoulder dislocation following reduction remains controversial. The two main options are immobilisation and arthroscopic stabilisation. The aim of this article is to highlight some of the issues that influence decision making when discussing management options with these patients, including natural history of the first time dislocation, outcomes of surgery and non-operative management particularly on the risk of future osteoarthritis (OA), the effects of delaying surgery and the optimal method of immobilisation. Extensive literature review was performed looking for previous publication addressing 4 points. i) Natural history of primary shoulder dislocation ii) Effect of surgical intervention on natural history iii) Risk of long term osteoarthritis with and without surgical intervention iv) Immobilisation techniques post reduction. Individuals younger than 25 years old are likely to re dislocate with non-operative management. Surgery reduces risk of recurrent instability. Patients with recurrent instability appear to be at a higher risk of OA. Those who have surgical stabilisation do not appear to be at a higher risk than those who dislocate just once, but are less likely to develop OA than those with recurrent instability. Delaying surgery makes the stabilisation more demanding due to elongation of capsule, progressive labro-ligamentous injury, prevalence and severity of glenoid bone loss. Recent studies have failed to match the preliminary outcomes associated with external rotation braces. Defining the best timing and type of treatment remains a challenge and should be tailored to each individual's age, occupation and degree of physical activity. PMID- 27200386 TI - A Chick Embryo in-Vitro Model of Knee Morphogenesis. AB - BACKGROUND: In this feasibility study, a mechanically loaded in-vitro tissue culture model of joint morphogenesis using the isolated lower extremity of the 8 day old chick embryo was developed to assess the effects of mechanical loading on joint morphogenesis. METHODS: The developed in-vitro system allows controlled flexion and extension of the chick embryonic knee with a range of motion of 20 degrees from a resting position of 90-100 degrees of flexion. Joint morphogenesis at 2, 3, 4 and 7 days of culture was assessed by histology and micro MRI in 4 specimen types: undisturbed in-ovo control embryos, in-ovo paralyzed embryos, in vitro unloaded limb cultures, and in-vitro loaded limb cultures. Relative glycosaminoglycan (GAG) concentration across the joint was assessed with an MRI technique referred to as dGEMRIC (delayed gadolinium enhanced MRI of cartilage) where T1 is proportional to glycosaminoglycan concentration. RESULTS: Average T1 over the entire tissue image for the normal control (IC) knee was 480 msec; for the 4 day loaded specimen average T1 was 354 msec; and for the 7 day loaded specimens T1 was 393 msec. The 4 day unloaded specimen had an average T1 of 279 msec while the 7 day unloaded specimen had an average T1 of 224 msec. The higher T1 values in loaded than unloaded specimens suggest that more glycosaminoglycan is produced in the loaded culture than in the unloaded preparation. CONCLUSION: Isolated limb tissue cultures under flexion-extension load can be viable and exhibit more progression of joint differentiation and glycosaminoglycan production than similarly cultured but unloaded specimens. However, when compared with controls consisting of intact undisturbed embryos in-ovo, the isolated loaded limbs in culture do not demonstrate equivalent amounts of absolute growth or joint differentiation. PMID- 27200387 TI - Analysis of the Geometry of the Distal Femur and Proximal Tibia in the Osteoarthritic Knee: A 3D Reconstruction CT Scan Based Study of 449 Cases. AB - BACKGROUND: The aim of this study is to evaluate the geometry of the distal femur and the proximal tibia in the osteoarthritic knee using 3D reconstructive CT scan imaging. METHODS: 449 patients with knee osteoarthritis were treated surgically in our center with patient-specific technology total knee arthroplasty. Preoperatively, all the patients underwent a CT scan according to a standard protocol. Using this database, the Hip-Knee-Angle (HKA), the Femur Valgus Angle (FVA), the Tibia Varus Angle (TVA), the Posterior Tibia Slope (PTS), and the angle between the posterior condylar axis and the anatomical transepicondylar axis (PCA) for each patient were recorded and statistically evaluated. RESULTS: In overall, the mean HKA angle was 177.3+/-5.55, the mean FVA angle was 3.19+/ 2.08, the mean TVA was 3.28+/-2.35, the PTS angle was 9.02+/-3.46, and the PCA angle was 2.86+/-0.78. Evaluation of the correlations between HKA and PCA (r=0.035), HKA and PTS (r=-0.047), and PCA and PTS (r=0.05) showed non significant relationships (P=0.46, P=0.32, and P=0.29 respectively). No significant differences were revealed from the comparison of male patients with female patients, regarding the mean HKA, FVA, TVA, PTS, and PCA. CONCLUSION: The posterior condylar axis is a well-defined but not a reliable axis, while the transepicondylar and the anteroposterior are reliable, but not easily defined axes. Given the large ranges and standard deviations of the location of posterior condylar axis, and the important inter- and intraobserver variability in the intraoperative location of the transepicondylar and the anteroposterior axes, the use of a preoperative 3D CT scan is recommended. PMID- 27200389 TI - Malnutrition in Joint Arthroplasty: Prospective Study Indicates Risk of Unplanned ICU Admission. AB - BACKGROUND: Malnutrition has been linked to poor outcomes after elective joint arthroplasty, but the risk of unplanned postoperative intensive care unit (ICU) admission in malnourished arthroplasty patients is unknown. METHODS: 1098 patients were followed as part of a prospective risk stratification program at a tertiary, high-volume arthroplasty center. Chronic malnutrition was defined as preoperative albumin <3.5 g/dL. RESULTS: The overall incidence of malnutrition was 16.9% (primary and revision arthroplasty patients). Average BMI was highest for patients in albumin category 3.0-3.5 (BMI 35.7). Preoperative albumin <3.0 and <3.5 g/dL translated to 15.4% and 3.8% rates of unplanned ICU admission, respectively, indicating nutritional status to be a factor in postoperative ICU admission. CONCLUSION: Patients with poor nutritional status must be counseled on the risks of adverse medical complications. PMID- 27200388 TI - Evaluation of Distal Femoral Rotational Alignment with Spiral CT Scan before Total Knee Arthroplasty (A Study in Iranian population). AB - BACKGROUND: Evaluating the landmarks for rotation of the distal femur is a challenge for orthopedic surgeons. Although the posterior femoral condyle axis is a good landmark for surgeons, the surgical transepicondylar axis may be a better option with the help of preoperative CT scanning. The purpose of this study was to ascertain relationships among the axes' guiding distal femur rotational alignment in preoperative CT scans of Iranian patients who were candidates for total knee arthroplasty and the effects of age, gender, and knee alignment on these relationships. METHODS: One hundred and eight cases who were admitted to two university hospitals for total knee arthroplasty were included in this study. The rotation of the distal femur was evaluated using single axial CT images through the femoral epicondyle. Four lines were drawn digitally in this view: anatomical and surgical transepicondylar axes, posterior condylar axis and the Whiteside anteroposterior line. The alignment of the extremity was evaluated in the standing alignment view. Then the angles were measured along these lines and their relationship was evaluated. RESULTS: The mean angle between the anatomical transepicondylar axis and posterior condylar axis and between the surgical transepicondylar axis and posterior condylar axis were 5.9 +/- 1.6 degrees and 1.6+/-1.7 degrees respectively. The mean angle between the Whiteside's anteroposterior line and the line perpendicular to the posterior condylar axis was 3.7+/-2.1 degrees. Significant differences existed between the two genders in these relationships. No significant correlation between the age of patients and angles of the distal femur was detected. The anatomical surgical transepicondylar axis was in 4.3 degrees external rotation in relation to the surgical transepicondylar axis. CONCLUSION: Preoperative CT scanning can help accurately determine rotational landmarks of the distal femur. If one of the reference axes cannot be determined, other reference axes can be used because of the good correlation between these landmarks. PMID- 27200390 TI - Pelvic Incidence in Patients with Hip Osteoarthritis. AB - BACKGROUND: Hip osteoarthritis (OA) is a major cause of pain and disability that results in considerable social and medical costs. Mechanics such as posture, alignment and orientation of the hips and the spinal column and the relationship between these factors have been implicated in the development of both hip and spine pathologies. This study aims to test the hypothesis if pelvic incidence varies in patients with and without osteoarthritis. We assessed the relationship between spinopelvic alignment as measured by pelvic incidence (PI) and the presence of hip OA. METHODS: We collected supine pelvis CT scans of 1,012 consecutive patients not known to have hip OA. Our first group consisted of 95 patients with moderate to severe hip OA as per radiology reports. The second group included 87 patients with no evidence of hip OA. Power analysis revealed the need for 77 patients per group to find a mean difference in PI of 5 degrees or less between both groups. Two trained physicians independently measured the PI to account for inter-observer reliability. RESULTS: Patients with moderate to severe hip OA had a mean PI of 56.5 degrees +/-12.8 degrees . The mean PI for patients without hip OA was 57.2 degrees +/-7.5 degrees . An independent samples t-test revealed no significant difference between the PI values of the two groups. Spearman's correlation coefficient of 0.754 demonstrated a high inter observer reliability. CONCLUSION: There was no difference in PI angle of hip OA patients and "healthy" patients. Our measurements of patients without OA were almost identical to the reported normal PI values in the literature. It appears that hip OA is not associated with PI angle, refuting the hypothesis made in previous studies, stating that elevated PI contributes to the future development of hip arthritis. CT scan seems to be a reliable and accurate way of assessing pelvic incidence. PMID- 27200391 TI - Position of the Patella among Emirati Adult Knees. Is Insall-Salvati Ratio Applicable to Middle-Easterners? AB - BACKGROUND: Abnormal patellar height is associated with anterior knee pain and several conditions that affect the patellofemoral joint. The aim of this study was to 1) report the incidence of patella alta and patella baja and 2) investigate whether the normal limits of the Insall-Salvati ratio is applicable in adult Middle-Easterners. METHODS: A radiographic review of the lateral radiographs of 736 Middle-Eastern knees were performed. Patellar tendon length (TL) and the patellar length (TP) was digitally measured and the ratios of these measures was used to calculate the Insall-Salvati ratio. RESULTS: The overall mean TL/PL ratio was 1.20+/-0.17. The Insall-Salvati ratio was higher (p=0.0013) in males (1.22+/- 0.12) than in females (1.18+/-0.17). According to our measurement, the recommended levels for defining abnormal patellar position should be 0.86 for patella baja and 1.54 for patella alta. CONCLUSION: The use of TL/PL ratio demonstrated a higher incidence of patella alta and a higher mean TL/PL ratio compared to other techniques. The normal ranges for the TL/PL differs from western populations and may be attributed to lifestyle differences. PMID- 27200392 TI - MRI-Arthroscopic Correlation in Rotator Cuff Tendon Pathologies; A Comparison between Various Centers. AB - BACKGROUND: Magnetic resonance imaging (MRI) has long been considered a perfect imaging study for evaluation of shoulder pathologies despite occasional discrepancies between MR reports and arthroscopic findings. In this study we aim to evaluate impact of imaging center as an indicator of image quality on accuracy of MRI reports in diagnosis of rotator cuff tendon pathologies. METHODS: We reviewed MR reports of 64 patients who underwent arthroscopy in university center hospital. MRIs were done in various centers including both university-affiliated and out-centers. All studies were reported by two radiologists in consensus unaware of the arthroscopic results or previous reports. An inter-observer agreement analysis using the kappa statistics was performed to determine consistency among imaging and surgical reports. RESULTS: Kappa values for out centers were as follows: 0.785 for biceps, 0.469 for suscapularis, 0.846 for supraspinatus and 0.785 for infraspinatus tendons. In university centers values were 0.799 for biceps, 0.802 for suscapularis, 0.789 for supraspinatus and 0.770 for infraspinatus tendons. CONCLUSION: Image reporting in university centers with proficient sequences increased accuracy of diagnosis in 3/4 of evaluated features and showed subtle decreased inter-observer agreement in 1/4 of features. Uniformity of the scanners and protocols as well as evaluation on a workstation rather than hard copies cumulatively resulted in a meaningful increase in the accuracy of the same radiologists in diagnosis of rotator cuff tendon tear. PMID- 27200393 TI - A Comparison of Hand Pain and Hand Function after Z-plasty Reconstruction of the Transverse Carpal Ligament with Traditional Median Neurolysis in Carpal Tunnel Syndrome. AB - BACKGROUND: Carpal tunnel syndrome is the most common focal mono-neuropathy. A study was designed to compare the effects of traditional open carpal tunnel release with median neurolysis and Z-plasty reconstruction of the transverse carpal ligament on post-operative hand pain and hand function in patients with idiopathic carpal tunnel syndrome. METHODS: Fifty-two patients with idiopathic carpal tunnel syndrome entered the study. The patients were randomly assigned into two groups to undergo simple transverse carpal ligament release or division of the ligament with Z-lengthening reconstruction. Forty-five patients completed the study. Two patients of the simple open surgery group and 5 patients of the Z plasty reconstruction group did not complete the follow up course. After the procedure, the patients were followed to assess post-operative pain and hand function during a 12-week period. RESULTS: The scores of hand pain on the first day after surgery were not statistically different between the two groups (P=0.213). But the score of hand pain was significantly lower in the Z-plasty reconstruction group at week 1, week 3, and week 6 after surgery (P<0.001). However, at week 12, no patient complained of hand pain in both groups. Considering hand function, no patient had normal hand grip after the first week, but after three weeks, a significantly higher proportion of patients in the Z plasty reconstruction group had reached near normal hand grip (76.1% vs. 29.1%;). However, at weeks 6 and 12, the differences were not statistically different between the two groups. CONCLUSION: We observed significant reduction in hand pain, shorter duration of hand pain and shorter period of time to reach normal hand grip by Z-plasty reconstruction of the TCL. PMID- 27200394 TI - Assessment of Decisional Conflict about the Treatment of carpal tunnel syndrome, Comparing Patients and Physicians. AB - BACKGROUND: As part of the process of developing a decision aid for carpal tunnel syndrome (CTS) according to the Ottawa Decision Support Framework, we were interested in the level of 'decisional conflict' of hand surgeons and patients with CTS. This study addresses the null hypothesis that there is no difference between surgeon and patient decisional conflict with respect to test and treatment options for CTS. Secondary analyses assess the impact of patient and physician demographics and the strength of the patient-physician relationship on decisional conflict. METHODS: One-hundred-twenty-three observers of the Science of Variation Group (SOVG) and 84 patients with carpal tunnel syndrome completed a survey regarding the Decisional Conflict Scale. Patients also filled out the Pain Self-efficacy Questionnaire (PSEQ) and the Patient Doctor Relationship Questionnaire (PDRQ-9). RESULTS: On average, patients had significantly greater decision conflict and scored higher on most subscales of the decisional conflict scale than hand surgeons. Factors associated with greater decision conflict were specific hand surgeon, less self-efficacy (confidence that one can achieve one's goals in spite of pain), and higher PDRQ (relationship between patient and doctor). Surgeons from Europe have--on average--significantly more decision conflict than surgeons in the United States of America. CONCLUSIONS: Patients with CTS have more decision conflict than hand surgeons. Decision aids might help narrow this gap in decisional conflict. PMID- 27200396 TI - Corrective Osteotomy for Intra-Articular Distal Humerus Malunion. AB - BACKGROUND: An intra-articular distal humerus malunion can be disabling. To improve function, reduce pain and/or prevent further secondary osteoarthritis an intra-articular corrective osteotomy can be considered. Herein we present the indications, practical guidelines for pre- operative planning and surgical technique. Subsequently, we provide long-term results in a small series. METHODS: We included six consecutive patients operated for intra-articular distal humerus malunion. Mean follow-up was 88 months. At lastest follow up elbow function was assessed according to standardized questionnaires and classification systems. RESULTS: All six patients healed their osteotomies. Three patients had a postoperative complication which were treated succesfully. Range of motion improved significantly and all patients were satisfied with the outcome. The elbow performance scores were good to excellent in all. Correlation analyses showed that age and level of osteoarthritis are very strong predictors for the long-term elbow function and quality of life. CONCLUSION: An intra-articular corrective osteotomy for a malunited distal humerus fracture is a worthwhile procedure. Based on our results it should particularly be considered in young patients with minimal osteoarthritis and moderate to severe functional disability and/or pain. PMID- 27200395 TI - Temporal and Spatial Expression of TGF-b1 in the Early Phase of Patellar Tendon Healing after Application of Platelet Rich Plasma. AB - BACKGROUND: The aim of this study is to find out the spatial and temporal expression of TGF-b1 during the tendon healing, after application of Platelet Rich Plasma (PRP). METHODS: A patellar tendon defect model in rabbits was used for this purpose. 48 skeletally mature New Zealand White rabbits, weighing 3.5 kg, were used for this study. Equal numbers of animals from both groups were sacrificed at 4 different time points (1st, 2nd, 3rd, and 4th week). A full thickness patellar tendon substance in the right limb of each animal was excised from its central portion during the operation. PRP with a gel form was applied and filled the tendon defect in PRP group. No PRP was applied in the tendon defect of controls. Histological sections with hematoxylin-eosin and immunohistochemical sections with an anti-TGF-b1 primary antibody were made for the evaluation of the results. RESULTS: A differentiation of the healing process was observed in the PRP group in comparison with the control group. TGF-b1 expression was detected in various cell populations (inflammatory cells, endothelial cells, macrophages, and tenocytes). Both cytoplasmic and nuclear expressions were present. The larger amounts of immunoexpression were localized in epitenon and in the repair site. PRP group showed stronger and more extensive staining at 1st and 2nd week (P<0.0001), whereas control group showed more extensive staining at the 3(rd) and 4(th) week (P<0.0001). CONCLUSIONS: Our study demonstrates that locally application of PRP result in an alteration of TGF-b1 expression during the healing of a patellar tendon defect. PMID- 27200397 TI - Aneurysmal Bone Cyst: An Analysis of 38 Cases and Report of Four Unusual Surface Ones. AB - Aneurysmal bone cyst (ABC) is a benign expansile bone tumor, most commonly involving the medulla of long bones. ABC rarely arises within the cortex or in the subperiosteal region, radiographically mimicking other conditions, in particular surface osteosarcomathat is low-grade in nature and may go secondary ABC changes, and telangiectatic osteosarcoma. Both of these are sometimes mistaken microscopically for primary ABC. We review the characteristics of ABC cases in our center and report four unusualsurface ABCs arising in the subperiosteal or cortical region of long bones, identified among 38 histologically proven ABCs during a four-year period in our center. The surface ABCs occurred at an older agewith a predilection for diaphysis of femur, tibia, and humerus. PMID- 27200398 TI - Treatment of Displaced Sacroiliac Fracture Using the Lateral Window for Short Plate Buttress Reduction and Percutaneous Sacroiliac Screw Fixation. AB - Fractures through the sacroiliac joint are very challenging to treat, technically difficult to reduce through closed methods on account of the multiaxial displacement of fractures fragments, frequently occur in very unwell patients, and have poor outcomes if malreduction is present. We describe a technique utilising the lateral window and a short buttress plate to reduce and stabilize the fragments prior to percutaneous fixation with sacroiliac screws. PMID- 27200399 TI - Interstitial Tear of the Subscapularis Tendon, Arthroscopic Findings and Technique of Repair. AB - Tears of the subscapularis tendon have been significantly recognized as a source of shoulder pain and dysfunction in the past decade, thanks to arthroscopic evaluation of the shoulder and biomechanical and anatomical studies of the tendon. Current classification of subscapularis tendon tear is based on insertion site of the tendon. Recently, a classification for non-insertional types of subscapularis tendon tear has been published. Interstitial tear of subscapularis tendon has not been described in classifications available in the literature. This report describes significant interstitial tear of the subscapularis tendon. This tear looks normal in superior, bursal and articular sides. Then its specific arthroscopic findings as "Air bag sign" and repair technique of the pathology is explained. PMID- 27200400 TI - Tailoring Tendon Transfer Surgery and Rehabilitation for a Musician: A Case Study. AB - Tendon transfers in hand patients are a commonly performed procedure after extensor tendon rupture. However, the standard side to side technique is not applicable in every patient. We present a case of a musician with unique demands to demonstrate the option to customize surgical technique and therapy regimen to the unique needs of each patient. An extensor indicis proprius to extensor digitorum communis transfer was performed in a 73 year old musician. A controlled active motion therapy protocol was followed. The patients musical practice regimen was incorporated into the therapy. The patient was able to independently extend her ring and small fingers in order to play her instrument and resumed play within one month postoperatively. A patient's functional goals including avocations need to be considered when selecting the appropriate surgical and therapeutic approach. PMID- 27200401 TI - Fanconi Anemia Concurrent with an Unusual Thumb Polydactyly: A Case Report. AB - This case report presents a case of Fanconi's Anemia with an unusual thumb polydactyly in a 2-year-old boy. The extra thumb had no nail, nail bed and distal phalanx. The extra thumb had no active motion. The duplication of the thumb occurred at the carpometacarpal joint but its morphology did not match with any classification described for thumb polydactyly. Although his thumb polydactyly was apparent at birth, Fanconi's anemia was not suspected until during a routine pre-operative laboratory test (CBC) for the elective surgery of his thumb. An early diagnosis of FA is important and the hand surgeons may be the first to have the opportunity to suspect and diagnose the underlying life threatening disorder. This case report presented an opportunity to diagnosis a fatal disorder by a routine pre operative laboratory test. To the best of my knowledge, the phenotype of the thumb polydactyly of the current case has not yet reported. PMID- 27200402 TI - Neglected Alkaptonuric Patient Presenting with Steppage Gait. AB - Even though intervertebral disc degeneration can be found in the natural course of alkaptonuria, detection of the disease by black disc color change in a patient without any other presentation of alkaptonuria is an exceptionally rare condition. We have reported a very rare case of alkaptonuria presented with low back pain and steppage gait in a 51-year-old male with a complaint of chronic low back pain and steppage gait who was operated on for prolapsed lumbar disc herniation. Intraoperatively his lumbar disk was discovered to be black. The alkaptonuria diagnosis was considered after histopathological examination of the black disc material and elevated urinary concentration of homogentisic acid confirmed the diagnosis. To our knowledge, this presentation has not been reported previously in literature. PMID- 27200404 TI - Comparison of organ-specific-radiation dose levels between 70 kVp perfusion CT and standard tri-phasic liver CT in patients with hepatocellular carcinoma using a Monte-Carlo-Simulation-based analysis platform. AB - PURPOSE: The aim of this study was to systematically compare organ-specific radiation dose levels between a radiation dose optimized perfusion CT (dVPCT) protocol of the liver and a tri-phasic standard CT protocol of the liver using a Monte-Carlo-Simulation-based analysis platform. METHODS AND MATERIALS: The complete CT data of 52 patients (41 males; mean age 65 +/- 12) with suspected HCC that underwent dVPCT examinations on a 3rd generation dual-source CT (Somatom Force, Siemens) with a dose optimized tube voltage of 70 kVp or 80 kVp were exported to an analysis platform (Radimetrics, Bayer). The dVPCT studies were matched with a reference group of 50 patients (35 males; mean age 65 +/- 14) that underwent standard tri-phasic CT (sCT) examinations of the liver with 130 kVp using the calculated water-equivalent-diameter of the patients. The analysis platform was used for the calculation of the organ-specific effective dose (ED) as well as global radiation-dose parameters (ICRP103). RESULTS: The organ specific ED of the dVPCT protocol was statistically significantly lower when compared to the sCT in 14 of 21, and noninferior in a total of 18 of 21 examined items (all p < 0.05). The EDs of the dVPCT examinations were especially in the dose sensitive organs such as the red marrow (17.3 mSv vs 24.6 mSv, p = < 0.0001) and the liver (33.3 mSv vs 46.9 mSv, p = 0.0003) lower when compared to the sCT. CONCLUSION: Our results suggest that dVPCT performed at 70 or 80 kVp compares favorably to sCT performed with 130 kVp with regard to effective organ dose levels, especially in dose sensitive organs, while providing additional functional information which is of paramount importance in patients undergoing novel targeted therapies. PMID- 27200405 TI - Retracted: Differential Evolution Algorithm with Diversified Vicinity Operator for Optimal Routing and Clustering of Energy Efficient Wireless Sensor Networks. AB - [This retracts the article DOI: 10.1155/2015/729634.]. PMID- 27200403 TI - Iranian Joint Registry (Iranian National Hip and Knee Arthroplasty Registry). AB - Periodic evaluation and monitoring the health and economic outcome of joint replacement surgery is a common and popular process under the territory of joint registries in many countries. In this article we introduce the methodology used for the foundation of the National Iranian Joint Registry (IJR) with a joint collaboration of the Social Security Organization (SSO) and academic research departments considering the requirements of the Iran's Ministry of Health and Education. PMID- 27200406 TI - Retracted: An Improved Differential Evolution Solution for Software Project Scheduling Problem. AB - [This retracts the article DOI: 10.1155/2015/232193.]. PMID- 27200407 TI - Retracted: Dynamic Harmony Search with Polynomial Mutation Algorithm for Valve Point Economic Load Dispatch. AB - [This retracts the article DOI: 10.1155/2015/147678.]. PMID- 27200408 TI - A New Surgical Approach for the Treatment of Conjunctivochalasis: Reduction of the Conjunctival Fold with Bipolar Electrocautery Forceps. AB - Aim. To report a new surgical technique for the treatment of conjunctivochalasis. Methods. A new surgical technique in which specially designed bipolar electrocautery forceps facilitate the complete reduction of the conjunctival folds without creating lesions near the corneoscleral limbus was designed. A retrospective revision of the medical records of patients treated with this technique between the years 2011 and 2013 was made, and eighteen eyes of sixteen patients with conjunctivochalasis treated with this new technique were included. Results. All the eyes treated showed a significant improvement with no evidence of scar lesions after a mean follow-up time of 10 months. Conclusions. The surgical technique presented here could be a good alternative for the management of conjunctivochalasis. PMID- 27200409 TI - Retracted: An Automatic Web Service Composition Framework Using QoS-Based Web Service Ranking Algorithm. AB - [This retracts the article DOI: 10.1155/2015/207174.]. PMID- 27200410 TI - Retracted: Medical Dataset Classification: A Machine Learning Paradigm Integrating Particle Swarm Optimization with Extreme Learning Machine Classifier. AB - [This retracts the article DOI: 10.1155/2015/418060.]. PMID- 27200411 TI - The Comparison of Lichtenstein Procedure with and without Mesh-Fixation for Inguinal Hernia Repair. AB - Aim. Although inguinal hernia repair is the most frequently performed surgical procedure in the world, the best repair method has not gained acceptance yet. The ideal repair must be safe, simple, and easy to perform and require minimal dissection which provides enough exploration, maintain patient's comfort in the early stage, and also be cost-effective, reducing operation costs, labor loss, hospital stay, and recurrence. Materials and Methods. There were eighty-five patients between the ages of 18 and 75, diagnosed with inguinal hernia in our clinic. Lichtenstein procedure for hernia repair was performed under spinal anesthesia in all patients. Forty-two patients had the standard procedure and, in 43 patients, the polypropylene mesh was used without fixation. All patients were examined and questioned on the 7th day of the operation in terms of pain, scrotal edema, and the presence of seroma and later on in the 6th postoperative month in terms of paresthesia, neuropraxia, and recurrence by a single physician. Results. Operative time and pain scores in the nonfixation group were significantly lower, without any increase in rates of recurrence. Conclusion. Based on these findings, in Lichtenstein hernia repair method, nonfixation technique can be used safely with better results. PMID- 27200412 TI - Perturbations of Respiratory Rhythm and Pattern by Disrupting Synaptic Inhibition within Pre-Botzinger and Botzinger Complexes. AB - The pre-Botzinger (pre-BotC) and Botzinger (BotC) complexes are the brainstem compartments containing interneurons considered to be critically involved in generating respiratory rhythm and motor pattern in mammals. Current models postulate that both generation of the rhythm and coordination of the inspiratory expiratory pattern involve inhibitory synaptic interactions within and between these regions. Both regions contain glycinergic and GABAergic neurons, and rhythmically active neurons in these regions receive appropriately coordinated phasic inhibition necessary for generation of the normal three-phase respiratory pattern. However, recent experiments attempting to disrupt glycinergic and GABAergic postsynaptic inhibition in the pre-BotC and BotC in adult rats in vivo have questioned the critical role of synaptic inhibition in these regions, as well as the importance of the BotC, which contradicts previous physiological and pharmacological studies. To further evaluate the roles of synaptic inhibition and the BotC, we bilaterally microinjected the GABAA receptor antagonist gabazine and glycinergic receptor antagonist strychnine into the pre-BotC or BotC in anesthetized adult rats in vivo and in perfused in situ brainstem-spinal cord preparations from juvenile rats. Muscimol was microinjected to suppress neuronal activity in the pre-BotC or BotC. In both preparations, disrupting inhibition within pre-BotC or BotC caused major site-specific perturbations of the rhythm and disrupted the three-phase motor pattern, in some experiments terminating rhythmic motor output. Suppressing BotC activity also potently disturbed the rhythm and motor pattern. We conclude that inhibitory circuit interactions within and between the pre-BotC and BotC critically regulate rhythmogenesis and are required for normal respiratory motor pattern generation. PMID- 27200413 TI - Mapping Cortical Responses to Somatosensory Stimuli in Human Infants with Simultaneous Near-Infrared Spectroscopy and Event-Related Potential Recording. AB - Near-infrared spectroscopy (NIRS) and electroencephalography (EEG) have recently provided fundamental new information about how the newborn brain processes innocuous and noxious somatosensory information. However, results derived independently from these two techniques are not entirely consistent, raising questions about the relationship between hemodynamic and electrophysiological responses in the study of touch and pain processing in the newborn. To address this, we have recorded NIRS and EEG responses simultaneously for the first time in the human infant following noxious (time-locked clinically required heel lances) and innocuous tactile cutaneous stimulation in 30 newborn infants. The results show that both techniques can be used to record quantifiable and distinct innocuous and noxious evoked activity at a group level in the newborn cortex. Noxious stimulation elicits a peak hemodynamic response that is 10-fold larger than that elicited by an innocuous stimulus (HbO2: 2.0 vs 0.3 uM) and a distinct nociceptive-specific N3P3 waveform in electrophysiological recordings. However, a novel single-trial analysis revealed that hemodynamic and electrophysiological responses do not always co-occur at an individual level, although when they do (64% of noxious test occasions), they are significantly correlated in magnitude. These data show that, while hemodynamic and electrophysiological touch and pain brain activity in newborn infants are comparable in group analyses, important individual differences remain. These data indicate that integrated and multimodal brain monitoring is required to understand central touch and pain processing in the newborn. PMID- 27200415 TI - Pharmacokinetic, biodistribution and therapeutic efficacy of 5-fluorouracil loaded pH-sensitive PEGylated liposomal nanoparticles in HCT-116 tumor bearing mouse. AB - The objective of the study was to investigate the pharmacokinetics and efficacy of 5-FU entrapped pH-sensitive liposomal nanoparticles with surface-modified anti epidermal growth factor receptor (EGFR) antibody (pHLNps-5-FU) delivery system. Cytotoxicity of 5-FU and pHLNps-5-FU was determined in vitro against HCT-116 cells. The biodistribution and pharmacokinetic parameters of the administered 5 FU and pHLNps-5-FU as well as efficacy of 5-FU and pHLNps-5-FU were determined in HCT-116 subcutaneous mouse model. Mean size of pHLNp-5-FU was 164.3 +/- 8.4 nm with entrapment efficiency (E.E) of 54.17%. While cytotoxicity of 5-FU and pHLNps 5-FU showed a strong dose-dependent, pHLNps-5-FU proved to be more effective (2-3 fold high) than that of 5-FU against HCT-116 cells. Pharmacokinetic study showed a prolonged plasma circulation of pHLNps-5-FU and a more significant body exposure while accumulation of pHLNps-5-FU in tumor was significantly higher than that of free 5-FU. Further, the efficacy of pHLNps-5-FU, was greater than free 5 FU at equivalent 5-FU dose. The study suggests that pHLNps may be an effective drug delivery system to enhance the anticancer activity of 5-FU against colorectal tumor growth. PMID- 27200414 TI - Quantifying Repetitive Transmission at Chemical Synapses: A Generative-Model Approach. AB - The dependence of the synaptic responses on the history of activation and their large variability are both distinctive features of repetitive transmission at chemical synapses. Quantitative investigations have mostly focused on trial averaged responses to characterize dynamic aspects of the transmission--thus disregarding variability--or on the fluctuations of the responses in steady conditions to characterize variability--thus disregarding dynamics. We present a statistically principled framework to quantify the dynamics of the probability distribution of synaptic responses under arbitrary patterns of activation. This is achieved by constructing a generative model of repetitive transmission, which includes an explicit description of the sources of stochasticity present in the process. The underlying parameters are then selected via an expectation maximization algorithm that is exact for a large class of models of synaptic transmission, so as to maximize the likelihood of the observed responses. The method exploits the information contained in the correlation between responses to produce highly accurate estimates of both quantal and dynamic parameters from the same recordings. The method also provides important conceptual and technical advances over existing state-of-the-art techniques. In particular, the repetition of the same stimulation in identical conditions becomes unnecessary. This paves the way to the design of optimal protocols to estimate synaptic parameters, to the quantitative comparison of synaptic models over benchmark datasets, and, most importantly, to the study of repetitive transmission under physiologically relevant patterns of synaptic activation. PMID- 27200416 TI - Age, Stigma, Adherence and Clinical Indicators in HIV-Infected Women. AB - Stigma has become a gendered phenomenon that affects increasing numbers of HIV infected women worldwide. This study examined the role of age as a possible moderator of the relationship between stigma and antiretroviral therapy adherence, CD4% and viral load among 120 HIV-infected women. A secondary analysis was conducted using data from the Keeping Healthy and Active with Risk Reduction and Medication Adherence (KHARMA) Project, an National Institutes of Health (NIH) funded randomized controlled trial to improve Antiretroviral treatment (ART) adherence and reduce risky behaviors in HIV-infected women at five clinical sites in a South-eastern city from 2005 to 2008. Stigma was measured using the Perceived Personal Stigma of Human Immunodeficiency Virus and Acquired Immune Deficiency Syndrome (HIV/AIDS) scale. Among participants <50 years old (n=90), age was significantly associated with viral load (rho=-.24, p=.02) and stigma was negatively associated with CD4% (r =-.26, p=.02). For the 30 participants >50 years old, age was not significantly associated with viral load, stigma or CD4%, and there was no significant association between stigma and CD4% (r=.07, p=.70). These findings indicate the need for further study regarding this potential moderating effect and possible interventions to address the susceptibility of younger women to the harmful effects of stigma. PMID- 27200417 TI - Gradient-Based Algorithm for Determining Tumor Volumes in Small Animals Using Planar Fluorescence Imaging Platform. AB - Planar fluorescence imaging is widely used in biological research because of its simplicity, use of non-ionizing radiation, and high-throughput data acquisition. In cancer research, where small animal models are used to study the in vivo effects of cancer therapeutics, the output of interest is often the tumor volume. Unfortunately, inaccuracies in determining tumor volume from surface-weighted projection fluorescence images undermine the data, and alternative physical or conventional tomographic approaches are prone to error or are tedious for most laboratories. Here, we report a method that uses a priori knowledge of a tumor xenograft model, a tumor-targeting near infrared probe, and a custom-developed image analysis planar view tumor volume algorithm (PV-TVA) to estimate tumor volume from planar fluorescence images. Our algorithm processes images obtained using near infrared light for improving imaging depth in tissue in comparison with light in the visible spectrum. We benchmarked our results against the actual tumor volume obtained from a standard water volume displacement method. Compared with a caliper-based method that has an average deviation from an actual volume of 18% (204.34 +/- 115.35 mm3), our PV-TVA average deviation from the actual volume was 9% (97.24 +/- 70.45 mm3; P < .001). Using a normalization-based analysis, we found that bioluminescence imaging and PV-TVA average deviations from actual volume were 36% and 10%, respectively. The improved accuracy of tumor volume assessment from planar fluorescence images, rapid data analysis, and the ease of archiving images for subsequent retrieval and analysis potentially lend our PV-TVA method to diverse cancer imaging applications. PMID- 27200418 TI - The Impact of Arterial Input Function Determination Variations on Prostate Dynamic Contrast-Enhanced Magnetic Resonance Imaging Pharmacokinetic Modeling: A Multicenter Data Analysis Challenge. AB - Dynamic contrast-enhanced MRI (DCE-MRI) has been widely used in tumor detection and therapy response evaluation. Pharmacokinetic analysis of DCE-MRI time-course data allows estimation of quantitative imaging biomarkers such as Ktrans(rate constant for plasma/interstitium contrast reagent (CR) transfer) and ve (extravascular and extracellular volume fraction). However, the use of quantitative DCE-MRI in clinical prostate imaging islimited, with uncertainty in arterial input function (AIF, i.e., the time rate of change of the concentration of CR in the blood plasma) determination being one of the primary reasons. In this multicenter data analysis challenge to assess the effects of variations in AIF quantification on estimation of DCE-MRI parameters, prostate DCE-MRI data acquired at one center from 11 prostate cancer patients were shared among nine centers. Each center used its site-specific method to determine the individual AIF from each data set and submitted the results to the managing center. Along with a literature population averaged AIF, these AIFs and their reference-tissue adjusted variants were used by the managing center to perform pharmacokinetic analysis of the DCE-MRI data sets using the Tofts model (TM). All other variables including tumor region of interest (ROI) definition and pre-contrast T1 were kept the same to evaluate parameter variations caused by AIF variations only. Considerable pharmacokinetic parameter variations were observed with the within subject coefficient of variation (wCV) of Ktrans obtained with unadjusted AIFs as high as 0.74. AIF-caused variations were larger in Ktrans than ve and both were reduced when reference-tissue-adjusted AIFs were used. The parameter variations were largely systematic, resulting in nearly unchanged parametric map patterns. The CR intravasation rate constant, kep (= Ktrans/ve), was less sensitive to AIF variation than Ktrans (wCV for unadjusted AIFs: 0.45 for kepvs. 0.74 for Ktrans), suggesting that it might be a more robust imaging biomarker of prostate microvasculature than Ktrans. PMID- 27200419 TI - Insulin decreases atherosclerosis by inducing endothelin receptor B expression. AB - Endothelial cell (EC) insulin resistance and dysfunction, caused by diabetes, accelerates atherosclerosis. It is unknown whether specifically enhancing EC targeted insulin action can decrease atherosclerosis in diabetes. Accordingly, overexpressing insulin receptor substrate-1 (IRS1) in the endothelia of Apoe-/- mice (Irs1/Apoe-/-) increased insulin signaling and function in the aorta. Atherosclerosis was significantly reduced in Irs1/ApoE-/- mice on diet-induced hyperinsulinemia and hyperglycemia. The mechanism of insulin's enhanced antiatherogenic actions in EC was related to remarkable induction of NO action, which increases endothelin receptor B (EDNRB) expression and intracellular [Ca2+]. Using the mice with knockin mutation of eNOS, which had Ser1176 mutated to alanine (AKI), deleting the only known mechanism for insulin to activate eNOS/NO pathway, we observed that IRS1 overexpression in the endothelia of Aki/ApoE-/- mice significantly decreased atherosclerosis. Interestingly, endothelial EDNRB expression was selectively reduced in intima of arteries from diabetic patients and rodents. However, endothelial EDNRB expression was upregulated by insulin via P13K/Akt pathway. Finally EDNRB deletion in EC of Ldlr /- and Irs1/Ldlr-/- mice decreased NO production and accelerated atherosclerosis, compared with Ldlr-/- mice. Accelerated atherosclerosis in diabetes may be reduced by improving insulin signaling selectively via IRS1/Akt in the EC by inducing EDNRB expression and NO production. PMID- 27200420 TI - Effects of aqueous extract from Asparagus officinalis L. roots on hypothalamic pituitary-gonadal axis hormone levels and the number of ovarian follicles in adult rats. AB - BACKGROUND: Asparagus is a plant with high nutritional, pharmaceutical, and industrial values. OBJECTIVE: The present study aimed to evaluate the effect of aqueous extract of asparagus roots on the hypothalamic-pituitary-gonadal axis hormones and oogenesis in female rats. MATERIALS AND METHODS: In this experimental study, 40 adult female Wistar rats were divided into five groups, which consist 8 rats. Groups included control, sham and three experimental groups receiving different doses (100, 200, 400 mg/kg/bw) of aqueous extract of asparagus roots. All dosages were administered orally for 28 days. Blood samples were taken from rats to evaluate serum levels of Gonadotropin releasing hormone (GnRH), follicular stimulating hormone (FSH), Luteinal hormone (LH), estrogen, and progesterone hormones. The ovaries were removed, weighted, sectioned, and studied by light microscope. RESULTS: Dose-dependent aqueous extract of asparagus roots significantly increased serum levels of GnRH, FSH, LH, estrogen, and progestin hormones compared to control and sham groups. Increase in number of ovarian follicles and corpus luteum in groups treated with asparagus root extract was also observed (p<0.05). CONCLUSION: Asparagus roots extract stimulates secretion of hypothalamic- pituitary- gonadal axis hormones. This also positively affects oogenesis in female rats. PMID- 27200421 TI - Effect of body weight on serum homocysteine level in patients with polycystic ovarian syndrome: A case control study. AB - BACKGROUND: Polycystic ovarian syndrome (PCOS) represent one of the common endocrine disorders which influence around 8% of reproductive women whom usually suffering from obesity and increase cardiovascular risk. Serum homocysteine levels are associated with bad impact on endothelial functions and considered as an independent risk factor for cardiovascular disease. OBJECTIVE: The aim was to study the level of plasma homocysteine in obese and non-obese Iraqi patients with PCOS. MATERIALS AND METHODS: This study was carried out on 207 women. Of theme, 101 women with PCOS and 106 PCOS- free women served as controls. Blood sample was taken from each participant on the 2(nd) day of menstruation morning after an overnight fasting. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), free testosterone and androstenedione were measured. Moreover, total lipid profile and plasma homocysteine levels were measured in both groups. RESULTS: Sixty percent of PCOS women were overweight or obese and 56% of them had a waist circumference >88cm. Moreover plasma homocysteine concentrations were found to be higher in patients with PCOS (11.5+/-5.41MUmol/L) as compared with control (8.10+/-1.89 MUmol/L) (p<0.002). Furthermore the homocysteine concentrations were 13.19+/-5.97 MUmol/L and 9.38+/-2.99 MUmol/L in both obese and normal-weight PCOS women respectively which was significantly higher than obese (p<0.002) and normal-weight (p<0.004) control women. CONCLUSION: Increase in body weight is not an independent risk factor to increase plasma homocysteine levels in PCOS women. PMID- 27200422 TI - Sexual dysfunction in infertile women. AB - BACKGROUND: Sexual problems have different effects on the life of people by influencing their interpersonal and marital relationships and satisfaction. Relationship between sexual dysfunctions and infertility can be mutual. Sexual dysfunction may cause difficulty conceiving but also attempts to conceive, may cause sexual dysfunction. OBJECTIVE: This paper compares sexual dysfunction in fertile and infertile women. MATERIALS AND METHODS: In this cross-sectional study, 110 infertile couples referring to Montasarieh Infertility Clinic and 110 fertile couples referring to five healthcare centers in Mashhad were selected by class cluster sampling method. Data collection tools included demographic questionnaire and Glombok-Rust Inventory of Sexual Satisfaction. Data were analyzed through descriptive and analytical statistical methods by SPSS. RESULTS: There was no significant difference in total score of sexual problems and other dimensions of sexual problems (except infrequency) in fertile 28.9 (15.5) and infertile 29.0 (15.4) women. Fertile women had more infrequency than infertile women (p=0.002). CONCLUSION: There was no significant difference between fertile and infertile women in terms of sexual problems. Paying attention to sexual aspects of infertility and presence of programs for training of sexual skills seems necessary for couples. PMID- 27200423 TI - Effect of Genistein on reproductive parameter and serum nitric oxide levels in morphine-treated mice. AB - BACKGROUND: The predominant phytoestrogen in soy and derived products is the isoflavone Genistein. Genistein has antioxidant properties. Morphine is a main psychoactive chemical in opium that can increase the generation of free radicals and therefore it could adversely affects the spermatogenesis. OBJECTIVE: The main goal was to investigate whether the Genistein could protect morphine adverse effects on sperm cells viability, count, motility, and testis histology and testosterone hormone and nitric oxide in blood serum. MATERIALS AND METHODS: In this study, various doses of Genistein (0, 1, 2, and 3 mg/kg) and Genistein plus morphine (0, 1, 2, and 3 mg/kg) were administered interaperitoneally to 48 male mice for 30 consequent days. These mice were randomly assigned to 8 groups (n=6) and sperm parameters (sperm cells viability, count, motility and morphology), testis weight and histology, testosterone hormone (ELISA method), FSH and LH hormones (immunoradiometry) and serum nitric oxide (griess assay) were analyzed and compared. RESULTS: The results indicated that morphine administration significantly decreased testosterone (0.03 ng/mg) LH and FSH level, histological parameters, count, viability (55.3%), morphology and motility of sperm cells (1%), testis weight (0.08 gr) and increase nitric oxide compared to saline group (p=0.00). However, administration of Genistein and Genistein plus morphine significantly boosted motility, morphology, count, viability of sperm cells, seminiferous tubules diameter, germinal thickness, testosterone, LH and FSH while decrease nitric oxide level in all groups compared to morphine group (p<0.025). CONCLUSION: It seems that Genistein administration could increase the quality of spermatozoa and prevent morphine- induced adverse effects on sperm parameters. PMID- 27200424 TI - The IL-6 -634C/G polymorphism: a candidate genetic marker for the prediction of idiopathic recurrent pregnancy loss. AB - BACKGROUND: Recurrent pregnancy loss (RPL) is defined as two or more miscarriages before the 20(th) week of gestation and its etiology is unknown in 50% of the cases. Interleukin 6 is an immune mediator, plays a regulatory role in embryo implantation and placental development. OBJECTIVE: The purpose was to assess the association between IL-6 -634C/G polymorphism and, susceptibility to idiopathic RPL for the first time in Iran. MATERIALS AND METHODS: In total 121 women with RPL and 121 healthy women as control group were enrolled in this case-control study. This study was performed from August 2013 to October 2014 in the Molecular Genetics Laboratory of Arsanjan University. Candidate polymorphism was evaluated by PCR-RFLP method on extracted genomic DNA. Data was analyzed using the statistical SPSS package. RESULTS: Our results showed an increased risk of RPL in patients with GG + GC genotype (OR=5.1, 95%CI: 1.04-25.3, p=0.04) in comparison to CC genotype. The frequency of mutant allele G in patients and controls was 0.75 and 0.66 respectively. The mutant allele G predisposes women to miscarriage 1.5 times greater than controls (OR=1.5, 95%CI: 1.03-2.27, p=0.036). The mean number of live births in RPL women (1.3+/-2.3) was significantly lower compared to control women (4.8+/-2.3). CONCLUSION: This study indicated that the promoter polymorphism (-634C/G) of the IL-6 gene has likely influence on individual susceptibility to RPL. PMID- 27200425 TI - Effect of acute lithium administration on penile erection: involvement of nitric oxide system. AB - BACKGROUND: Lithium has been the treatment of choice for bipolar disorder (BD) for many years. Although erectile dysfunction is a known adverse effect of this drug, the mechanism of action by which lithium affects erectile function is still unknown. OBJECTIVE: The aim was to investigate the possible involvement of nitric oxide (NO) in modulatory effect of lithium on penile erection (PE). We further evaluated the possible role of Sildenafil in treatment of lithium-induced erectile dysfunction. MATERIALS AND METHODS: Erectile function was determined using rat model of apomorphine-induced erections. For evaluating the effect of lithium on penile erection, rats received intraperitoneal injection of graded doses of lithium chloride 30 mins before subcutaneous injection of apomorphine. To determine the possible role of NO pathway, sub-effective dose of N (G)-nitro-L arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, was administered 15 min before administration of sub-effective dose of lithium chloride. In other separate experimental groups, sub- effective dose of the nitric oxide precursor, L-arginine, or Sildenafil was injected into the animals 15 min before administration of a potent dose of lithium. 30 min after administration of lithium chloride, animals were assessed in apomorphine test. Serum lithium levels were measured 30 min after administration of effective dose of lithium. RESULTS: Lithium at 50 and 100 mg/kg significantly decreased number of PE (p<0.001), whereas at lower doses (5, 10 and 30 mg/kg) had no effect on apomorphine induced PE. The serum Li+ level of rats receiving 50 mg/kg lithium was 1+/-0.15 mmol/L which is in therapeutic range of lithium. The inhibitory effect of Lithium was blocked by administration of sub-effective dose of nitric oxide precursor L-arginine (100 mg/kg) (p<0.001) and sildenafil (3.5 mg/kg) (p<0.001) whereas pretreatment with a low and sub-effective dose of L-NAME (10mg/kg) potentiated sub-effective dose of lithium, (p<0.001). CONCLUSION: These results suggest acute treatments with lithium cause erectile dysfunction in an in vivo rat model. Furthermore it seems that the NO pathway might play role in erectile dysfunction associated with lithium treatment. Findings also suggest that Sildenafil may be effective in treatment of lithium-associated erectile dysfunction. PMID- 27200426 TI - Comparison of sexual dysfunction in women with infertility and without infertility referred to Al-Zahra Hospital in 2013-2014. AB - BACKGROUND: One of the affected aspects in infertile women that have not been given sufficient attention is sexual function. Sexual function is a key factor in physical and marital health, and sexual dysfunction could significantly lower the quality of life. Aim of this study was to assess the comparison sexual dysfunction in women with infertility and without infertility, admitted to Al- Zahra Hospital. OBJECTIVE: We decided to assess the prevalence of women sexual disorders in fertile and infertile subjects, admitted to Al-Zahra Hospital. MATERIALS AND METHODS: 149 fertile and 147 infertile women who referred to infertility clinic of Al-Zahra Hospital during 2013-2014 were entered this cross sectional study and Female Sexual Function Index questionnaire (FSFI) had been filled by all the cases. Most of women were married for 6-10 years (35.5%) and mean marriage time in participants was 9.55+/-6.07 years. Data were analyzed using SPSS software Ver. 18 and (2) test and logistic regression model has been used for analysis. RESULTS: Results showed significant differences between desire (p=0.004), arousal (p=0.001), satisfaction (p=0.022) and total sexual dysfunction (p=0.011) in both groups but in lubrication (p=0.266), orgasm (p=0.61) and pain (p=0.793) difference were not significant. CONCLUSION: Some of sexual dysfunction indices are high in all infertile women. Our findings suggest that infertility impacts on women's sexual function in desire, arousal, satisfaction and total sexual dysfunction. Health care professional should be sensitive to impact that diagnosis of infertility can have on women's sexuality. PMID- 27200427 TI - The effect of Non- ionizing electromagnetic field with a frequency of 50 Hz in Rat ovary: A transmission electron microscopy study. AB - BACKGROUND: Recently, there are increasing concerns and interests about the potential effects of Electromagnetic Field (EMF) on both human and animal health. OBJECTIVE: The goal of this study was to evaluate the harmful effects of 50 Hz non-ionizing EMF on rat oocytes. MATERIALS AND METHODS: In this experimental study 30 rats were randomly taken from laboratory animals and their ags and weights were determined. These 3 month's old rats were randomly divided into 3 groups. The control group consisted of 10 rats without receiving any treatment and kept under normal conditions. Experimental group 1 (10 rats) received EMF for 8 weeks (3 weeks intrauterine +5 weeks after births) and experimental group 2 (10 rats) received EMF for 13 weeks (3 weeks intrauterine +10 weeks after birth). After removing the ovaries and isolating follicles, granulosa cells were fixed in glutaraldehyde and osmium tetroxide. Electron microscopy was used to investigate the traumatic effects of EMF on follicles. RESULTS: In control group nucleus membrane and mitochondria in follicle's cytoplasm seemed normal in appearance. Theca layer of primary follicles in experimental group was separated clearly, zona layer demonstrated trot with irregular thickness and ovarian stroma seemed isolated with dilated vessels showing infiltration. CONCLUSION: According to the results of this study, it can be concluded that EMF has harmful effects on the ovarian follicles. PMID- 27200428 TI - Protective effect of methanolic extract of Berberis integerrima Bunge. root on carbon tetrachloride-induced testicular injury in Wistar rats. AB - BACKGROUND: Tissue protective effect of compounds with antioxidant properties has been demonstrated. The alkaloids found in barberry root are considered as antioxidants. OBJECTIVE: According to barberry protective effects in different tissues, in this study, the protective effect of Berberis integerrima Bge. root )MEBIR) was evaluated against CCl4-induced testicular damages in Wistar rats. MATERIALS AND METHODS: 40 mature male rats were randomly divided into 5 groups: 1: Normal control, 2: Sham: received CCl4 diluted in olive oil (50% v/v; 1ml/kg bw), intraperitoneally, twice a week for 4 weeks, 3 and 4: Sham rats treated with MEBIR (250 and 500 mg/kg bw) for 28 days, 5: Sham rats treated with silymarin (50 mg/kg bw) for 28 days. After 28 days, serum testosterone level, absolute testis weight, catalase activity, malondialdehyde level, and histological parameters were investigated. RESULTS: In the treated rats with MEBIR (250 and 500 mg/kg bw) or silymarin (50 mg/kg bw), there was a significant increase in the absolute testis weight, testosterone level, seminiferous tubules diameter (p<0.001), thickness of the epithelium, tubule differentiation index) p<0.001), spermiogenesis index (p<0.001), the activity of catalase, and a significant decrease in interstitial tissue thickness (p<0.001) and malondialdehyde level in comparison with CCl4-treated group. The effect of the MEBIR at dose of 500 mg/kg bw is more than that of the standard drug, silymarin (50 mg/kg bw). CONCLUSION: From the results, it is suggested that the protective effects of MEBIR is possibly due to antioxidant effects of its bioactive compounds. PMID- 27200429 TI - Coadministration of calcium chloride with lead acetate can improve motility of cauda epididymal spermatozoa in Swiss white mice. AB - BACKGROUND: Lead is an industrial heavy metal that can decrease sperm motility. OBJECTIVE: The aim was to investigate the protective effects of calcium against lead on motility of spermatozoa. MATERIALS AND METHODS: In total 40 adult male Swiss white mice were randomly divided into 5 groups (control, lead of 1(st) wk, lead of 2(nd) wk, lead/calcium of 1(st) wk and lead/calcium of 2(nd) wk). The lead groups of mice were injected by a single dose of lead acetate (200 mg/kg) intraperitoneally. Lead/calcium groups of mice were injected by a single same dose of lead acetate along with three doses of 80 mg/kg calcium chloride. The control group of mice was injected only with same volume of distilled water through the same route. Mice of 1(st) and 2(nd) wk groups were sacrificed through cervical dislocation one and two weeks after injections respectively. RESULTS: Mean of the progressive motile spermatozoa of cauda epididymis in lead/calcium group of the first week was higher than the lead group of the first week and this difference was significant. There was not any significant difference among weight of testes and epididymides of all groups. CONCLUSION: It can be concluded that calcium can decrease the effects of lead on sperm motility. PMID- 27200430 TI - Quantitative Evaluation of MDP-Ca Salt and DCPD after Application of an MDP-based One-step Self-etching Adhesive on Enamel and Dentin. AB - PURPOSE: To investigate the effects of an experimental 10-methacryloyloxydecyl dihydrogen phosphate (MDP)-based one-step self-etching adhesive (EX adhesive) applied to enamel and dentin on the production of calcium salt of MDP (MDP-Ca salt) and dicalcium phosphate dehydrate (DCPD) at various periods. MATERIALS AND METHODS: The EX adhesive was prepared. Bovine enamel and dentin reactants were prepared by varying the application period of the EX adhesive: 0.5, 1, 5, 30, 60 and 1440 min. Enamel and dentin reactants were analyzed using x-ray diffraction and solid-state phosphorus-31 nuclear magnetic resonance (31P NMR). Curvefitting analyses of corresponding 31P NMR spectra were performed. RESULTS: Enamel and dentin developed several types of MDP-Ca salts and DCPDs with amorphous and crystalline phases throughout the application period. The predominant molecular species of MDP-Ca salt was determined as the monocalcium salt of the MDP monomer. Dentin showed a faster production rate and greater produced amounts of MDP-Ca salt than did enamel, since enamel showed a knee-point in the production rate of the MDP-Ca salt at the application period of 5 min. In contrast, enamel developed greater amounts of DCPD than did dentin and two types of DCPDs with different crystalline phases at application periods > 30 min. The amounts of MDP-Ca salt developed during the 30-s application of the EX adhesive on enamel and dentin were 7.3 times and 21.2 times greater than DCPD, respectively. CONCLUSION: The MDP-based one-step adhesive yielded several types of MDP-Ca salts and DCPD with an amorphous phase during the 30-s application period on enamel and dentin. PMID- 27200431 TI - Short- and Long-term Evaluation of Dentin-Resin Interfaces Formed by Etch-and Rinse Adhesives on Plasma-treated Dentin. AB - PURPOSE: To investigate the influence of atmospheric pressure plasma (APP) treatment on the microtensile dentin bond strength of two etch-and-rinse adhesive systems, after one week and one year of water storage, and additionally to observe the micromorphology of resin/dentin interfaces under scanning electronic microscopy (SEM). MATERIALS AND METHODS: The occlusal enamel was removed from third human molars to expose a flat dentin surface. The teeth were then randomly divided into six groups (n = 7), according to two adhesives (Optibond FL and XP Bond) and three APP treatments (untreated dentin [control], APP application before or after acid etching). After performing the composite resin buildup on bonded dentin, the teeth were sectioned perpendicularly to the bonded interface to obtain beam-shaped specimens (cross-sectional area of ~0.9 mm2). The specimens were tested in tension until failure after one week and one year of water storage (1.0 mm/min rate). Bond strength data were analyzed by three-way ANOVA and Tukey's post-hoc test (alpha = 0.05%). Bonded beam specimens from each tooth were also prepared for interfacial SEM investigation. RESULTS: At one week, APP treatment applied after acid etching increased the dentin bond strength for XP Bond, while no effect was observed for Optibond FL. After one year, the bond strength of XP Bond decreased in groups where APP was applied after etching. The evaluation time did not influence the bond strength for Optibond FL. CONCLUSION: One-year evaluation did not show any sign of degradation of interfacial structures in any group. Application of APP to etched dentin combined with a two step etch-and-rinse adhesive significantly increased bond strength at one week, but the effect was not stable after one year and was adhesive dependent. PMID- 27200432 TI - Morphological Evaluation of the Adhesive/Enamel interfaces of Two-step Self etching Adhesives and Multimode One-bottle Self-etching Adhesives. AB - PURPOSE: To evaluate the acid-base resistant zone (ABRZ) at the adhesive/enamel interface of self-etching adhesives with or without prior phosphoric acid etching. MATERIALS AND METHODS: Four adhesives were used in 8 groups: Clearfil SE Bond (SEB), Optibond XTR (XTR), Scotchbond Universal Adhesive (SBU), and Clearfil BOND SE ONE (ONE) without prior phosphoric-acid etching, and each adhesive with phosphoric acid etching for 10 s (P-SEB, P-XTR, P-SBU and P-ONE, respectively). After application of self-etching adhesives on ground enamel surfaces of human teeth, a flowable composite was placed. For observation of the acid-base resistant zone (ABRZ), the bonded interface was exposed to demineralizing solution (pH 4.5) for 4.5 h, followed by 5% NaOCl with ultrasonication for 20 min. After the acid-base challenge, morphological attributes of the interface were observed using SEM. RESULTS: ABRZ formation was confirmed in all groups. The funnel-shaped erosion beneath the interface was present in SBU and ONE, where nearly 10 to 15 MUm of enamel was dissolved. With phosphoric acid etching, the ABRZs were obviously thicker compared with no phosphoric acid etching. CONCLUSION: Enamel beneath the bonding interface was more susceptible to acid dissolution in SBU and ONE. In the case of the one-bottle self-etching adhesives and universal adhesives that intrinsically have higher pH values, enamel etching should be recommended to improve the interfacial quality. PMID- 27200433 TI - Glass Fiber Post/Composite Core Systems Bonded to Human Dentin: Analysis of Tensile Load vs Calculated Tensile Strength of Various Systems Using Pull-out Tests. AB - PURPOSE: Pull-out testing was used to determine the tensile load (TL) and tensile strength (TS) of five different fiber post systems bonded to human intracanal dentin. MATERIALS AND METHODS: 120 caries-free premolars, canines, and maxillary central incisors were divided into 5 different groups for 5 fiber post systems (n = 24): 1. RelyX Fiber Post 3D (RX3D); 2. RelyX Fiber Post (RX); 3. Luxa- Post (LP); 4. FibreKleer 4X Tapered Post (FK); 5. ParaPost Taper Lux (PP). The teeth were prepared and posts inserted. Core buildups were performed with the corresponding product's resin composite. All specimens were stored in water for 24 h at 37 degrees C. TL and TS were tested on half of the specimens (n = 12/group). The remaining samples were thermocycled (10,000 x 5 degrees C/55 degrees C) before testing. TL was directly measured and TS was calculated using the bonding surface. Failure modes were identified using a stereomicroscope. Data were analyzed using twoway ANOVA with the post-hoc Scheffe test, as well as the chi-squared test (p < 0.05). RESULTS: FK and LP resulted in the lowest mean TL but were not significantly different from those of RX and RX3D. The highest mean TL and TS were observed for PP. Nevertheless, PP fell within the same statistical subset as RX3D and RX. Thermocycling showed no impact on the results. RX3D predominantly showed debonding of the post plus core buildup from the tooth; all other systems mainly demonstrated detachment of the core from the posts. CONCLUSION: PP, RX, and RX3D together with an adhesive core buildup yielded the highest bond strength to human dentin. Parameters TL and TS showed the same tendencies and statistical evidence. PMID- 27200434 TI - Different Strategies to Bond Bis-GMA-based Resin Cement to Zirconia. AB - PURPOSE: To evaluate the effect of different bonding strategies on short- and long-term bis-GMA-based resin cement bond strengths to zirconia. MATERIALS AND METHODS: One hundred twenty samples of fully-sintered zirconia (Prettau Zirconia) were sandblasted and randomly distributed into 5 groups (n = 24): UA: Scotchbond Universal Adhesive; SZP: Signum Zirconia Bond I + II; ZPP: Z-Prime Plus; EXP: MZ experimental primer; CO: no primer application (control). After performing these surface treatments, translucent tubes (0.8 mm diameter and 1.0 mm height) were placed on the zirconia specimens, and bis-GMA-based cement (Duo-Link) was injected into them and light cured. Specimens were tested for microshear bond strength either 24 h or 6 months (m) after water storage (37 degrees C) and surfaces were characterized by SEM and EDX. Two-way ANOVA and Tukey's post-hoc test (p < 0.05) were used to evaluate bond strength results. RESULTS: The mean bond strengths (MPa +/- SD) were: UA=14.6 +/- 4.7a (24 h); 16.0 +/- 4.8a (6 m); SZP = 14.0 +/- 5.4ab (24 h); 11.9 +/- 2.6ab (6 m); ZPP=8.0 +/- 1.8b (24 h); 8.6 +/- 3.3b (6 m); EXP = 1.2 +/- 0.5c (24 h); 0.6 +/- 0.7c (6 m); CO=1.0 +/- 1.2c (24 h); 1.3 +/- 1.2c (6 m). Bonding strategy significantly influenced bond strength (p = 0.0001), but storage time did not (p = 0.841). Groups UA and SZP showed a homogeneous layer covering the zirconia surface. In these groups, EDX demonstrated the presence of phosphorus. Group ZPP resulted in a nonhomogeneous layer, exposing the zirconia substrate underneath. EXP application resulted in an undetectable layer. CONCLUSION: Water storage did not affect resin cement bond strengths to zirconia irrespective of the surface treatment. Bis-GMA-based resin cement bond strengths to zirconia are affected by specific bonding strategies. PMID- 27200435 TI - Characterisation of gold catalysts. AB - Au-based catalysts have established a new important field of catalysis, revealing specific properties in terms of both high activity and selectivity for many reactions. However, the correlation between the morphology and the activity of the catalyst is not always clear although much effort has been addressed to this task. To some extent the problem relates to the complexity of the characterisation techniques that can be applied to Au catalyst and the broad range of ways in which they can be prepared. Indeed, in many reports only a few characterization techniques have been used to investigate the potential nature of the active sites. The aim of this review is to provide a critical description of the techniques that are most commonly used as well as the more advanced characterization techniques available for this task. The techniques that we discuss are (i) transmission electron microscopy methods, (ii) X-ray spectroscopy techniques, (iii) vibrational spectroscopy techniques and (iv) chemisorption methods. The description is coupled with developing an understanding of a number of preparation methods. In the final section the example of the supported AuPd alloy catalyst is discussed to show how the techniques can gain an understanding of an active oxidation catalyst. PMID- 27200436 TI - Template-free electrodeposition of AlFe alloy nanowires from a room-temperature ionic liquid as an anode material for Li-ion batteries. AB - AlFe alloy nanowires were directly electrodeposited on copper substrates from trimethylamine hydrochloride (TMHC)-AlCl3 ionic liquids with small amounts of FeCl3 at room temperature without templates. Coin cells composed of AlFe alloy nanowire electrodes and lithium foils were assembled to characterize the alloy electrochemical properties by galvanostatic charge/discharge tests. Effects of FeCl3 concentration, potential and temperature on the alloy morphology, composition and cyclic performance were examined. Addition of Fe into the alloy changed the nanowires from a 'hill-like' bulk morphology to a free-standing morphology, and increased the coverage area of the alloy on Cu substrates. As an inactive element, Fe could also buffer the alloys' large volume changes during Li intercalation and deintercalation. AlFe alloy nanowires composed of a small amount of Fe with an average diameter of 140 nm exhibited an outstanding cyclic performance and delivered a specific capacity of about 570 mA h g(-1) after 50 cycles. This advanced template-free method for the direct preparation of high performance nanostructure AlFe alloy anode materials is quite simple and inexpensive, which presents a promising prospect for practical application in Li ion batteries. PMID- 27200437 TI - Temperature dependence of the electrode potential of a cobalt-based redox couple in ionic liquid electrolytes for thermal energy harvesting. AB - Increasing the application of technologies for harvesting waste heat could make a significant contribution to sustainable energy production. Thermoelectrochemical cells are one such emerging technology, where the thermal response of a redox couple in an electrolyte is used to generate a potential difference across a cell when a temperature gradient exists. The unique physical properties of ionic liquids make them ideal for application as electrolytes in these devices. One of the keys to utilizing these media in efficient thermoelectrochemical cells is achieving high Seebeck coefficients, Se: the thermodynamic quantity that determines the magnitude of the voltage achieved per unit temperature difference. Here, we report the Se and cell performance of a cobalt-based redox couple in a range of different ionic liquids, to investigate the influence of the nature of the IL on the thermodynamics and cell performance of the redox system. The results reported include the highest Se to-date for an IL-based electrolyte. The effect of diluting the different ILs with propylene carbonate is also reported, which results in a significant increase in the output powers and current densities of the device. PMID- 27200438 TI - Photodeoxygenation of dinaphthothiophene, benzophenanthrothiophene, and benzonaphthothiophene S-oxides. AB - Photoinduced deoxygenation of dibenzothiophene S-oxide (DBTO) has been suggested to release atomic oxygen [O((3)P)]. To expand the conditions and applications where O((3)P) could be used, generation of O((3)P) at longer wavelengths was desirable. The sulfoxides benzo[b]naphtho-[1,2,d]thiophene S-oxide, benzo[b]naphtho[2,1,d]thiophene S-oxide, benzo[b]phenanthro[9,10-d]thiophene S oxide, dinaphtho[2,1-b:1',2'-d]thiophene S-oxide, and dinaphtho[1,2-b:2',1' d]thiophene S-oxide all absorb light at longer wavelengths than DBTO. To determine if these sulfoxides could be used to generate O((3)P), quantum yield studies, product studies, and computational analysis were performed. Quantum yields for the deoxygenation were up to 3 times larger for these sulfoxides compared to DBTO. However, oxidation of the solvent by these sulfoxides resulted in different ratios of oxidized products compared to DBTO, which suggested a change in deoxygenation mechanism. Density functional calculations revealed a much larger singlet-triplet gap for the larger sulfoxides compared to DBTO. This led to the conclusion that the examined sulfoxides could undergo deoxygenation by two different mechanisms. PMID- 27200439 TI - Toward food analytics: fast estimation of lycopene and beta-carotene content in tomatoes based on surface enhanced Raman spectroscopy (SERS). AB - Carotenoids are molecules that play important roles in both plant development and in the well-being of mammalian organisms. Therefore, various studies have been performed to characterize carotenoids' properties, distribution in nature and their health benefits upon ingestion. Nevertheless, there is a gap regarding a fast detection of them at the plant phase. Within this contribution we report the results obtained regarding the application of surface enhanced Raman spectroscopy (SERS) toward the differentiation of two carotenoid molecules (namely, lycopene and beta-carotene) in tomato samples. To this end, an e-beam lithography (EBL) SERS-active substrate and a 488 nm excitation source were employed, and a relevant simulated matrix was prepared (by mixing the two carotenoids in defined percentages) and measured. Next, carotenoids were extracted from tomato plants and measured as well. Finally, a combination of principal component analysis and partial least squares regression (PCA-PLSR) was applied to process the data, and the obtained results were compared with HPLC measurements of the same extracts. A good agreement was obtained between the HPLC and the SERS results for most of the tomato samples. PMID- 27200440 TI - Preface. PMID- 27200441 TI - Retraction notice to: ''Copper-doped borosilicate bioactive glass scaffolds with improved angiogenic and osteogenic capacity for repairing osseous defects" [Acta Biomater. 14 (2015) 185-196]. PMID- 27200442 TI - A Vesalian guide to neuroscience. PMID- 27200443 TI - Self-tolerance revisited. PMID- 27200444 TI - Bridging bioethics and biology. PMID- 27200445 TI - Metaphors and tracers: Radioactivity in twentieth-century biology. PMID- 27200446 TI - Authors' reply. PMID- 27200447 TI - Peer review: Close inspection. PMID- 27200448 TI - Relationships: Doctor's advice. PMID- 27200449 TI - Trade talk: Cell negotiator. PMID- 27200452 TI - Do I Have a Story for You. PMID- 27200450 TI - [Juan Antonio Gomez Gerique]. PMID- 27200453 TI - [Research on Electrical Impedance Tomography Technology]. AB - This article reviews the principle of electrical impedance tomography imaging and measurement system; focuses on electrical impedance tomography imaging detection system of incentive mode and several typical image reconstruction algorithm of electrical impedance imaging; and objectively compares and effectively evaluates several image reconstruction algorithm. PMID- 27200454 TI - Macrocyclic Tetraimines: Synthesis and Reversible Uptake of Diethyl Phthalate by a Porous Macrocycle. AB - The imine bond has attracted much attention for the synthesis of macrocycles used to construct porous materials. In the present article, we report on the synthesis of two series of isomeric macrocyclic tetraimines based on bis-alkynylbenzene diamines. Under heterogeneous solid-liquid conditions the condensation of the diamines with isophthalaldehyde or terephthaldehyde afforded mainly the corresponding [2 + 2] adducts. Among the eight macrocycles studied, only the macrocycle 1 has a porous structure. The article describes not only the synthesis of these macrocycles but also the encountered difficulties during their preparation. Finally, we expand the use of 1a as a porous solid support by studying its reversible and preferential liquid-solid adsorption properties for diethyl phthalate in front of other commercial phthalates. PMID- 27200455 TI - Deep Learning Applications for Predicting Pharmacological Properties of Drugs and Drug Repurposing Using Transcriptomic Data. AB - Deep learning is rapidly advancing many areas of science and technology with multiple success stories in image, text, voice and video recognition, robotics, and autonomous driving. In this paper we demonstrate how deep neural networks (DNN) trained on large transcriptional response data sets can classify various drugs to therapeutic categories solely based on their transcriptional profiles. We used the perturbation samples of 678 drugs across A549, MCF-7, and PC-3 cell lines from the LINCS Project and linked those to 12 therapeutic use categories derived from MeSH. To train the DNN, we utilized both gene level transcriptomic data and transcriptomic data processed using a pathway activation scoring algorithm, for a pooled data set of samples perturbed with different concentrations of the drug for 6 and 24 hours. In both pathway and gene level classification, DNN achieved high classification accuracy and convincingly outperformed the support vector machine (SVM) model on every multiclass classification problem, however, models based on pathway level data performed significantly better. For the first time we demonstrate a deep learning neural net trained on transcriptomic data to recognize pharmacological properties of multiple drugs across different biological systems and conditions. We also propose using deep neural net confusion matrices for drug repositioning. This work is a proof of principle for applying deep learning to drug discovery and development. PMID- 27200456 TI - Ruthenium-Catalyzed Enantioselective Hydrogenation of 1,8-Naphthyridine Derivatives. AB - The first asymmetric hydrogenation of 2,7-disubstituted 1,8-naphthyridines catalyzed by chiral cationic ruthenium diamine complexes has been developed. A wide range of 1,8-naphthyridine derivatives were effectively hydrogenated to give 1,2,3,4-tetrahydro-1,8-naphthyridines with up to 99% ee and full conversions. The method provides a practical and facile approach to the preparation of valuable chiral heterocyclic building blocks and useful motifs for a new kind of P,N ligand. PMID- 27200457 TI - EndoSd: an IgG glycan hydrolyzing enzyme in Streptococcus dysgalactiae subspecies dysgalactiae. AB - AIM: The aim of this study was to identify and characterize EndoS-like enzymes in Streptococcus dysgalactiae subspecies dysgalactiae (SDSD). MATERIALS & METHODS: PCR, DNA sequencing, recombinant protein expression, lectin blot, ultra high performance liquid chromatography analysis and a chitinase assay were used to identify ndoS-like genes and characterize EndoSd. RESULTS: EndoSd were found in four SDSD strains. EndoSd hydrolyzes the chitobiose core of the glycan on IgG. The amino acid sequence of EndoSd is 70% identical to EndoS in S. pyogenes, but it has a unique C-terminal sequence. EndoSd secretion is influenced by the carbohydrate composition of the growth medium. CONCLUSION: Our findings indicate that IgG glycan hydrolyzing activity is present in SDSD, and that the activity can be attributed to the here identified enzyme EndoSd. PMID- 27200458 TI - Significantly Increasing the Ductility of High Performance Polymer Semiconductors through Polymer Blending. AB - Polymer semiconductors based on donor-acceptor monomers have recently resulted in significant gains in field effect mobility in organic thin film transistors (OTFTs). These polymers incorporate fused aromatic rings and have been designed to have stiff planar backbones, resulting in strong intermolecular interactions, which subsequently result in stiff and brittle films. The complex synthesis typically required for these materials may also result in increased production costs. Thus, the development of methods to improve mechanical plasticity while lowering material consumption during fabrication will significantly improve opportunities for adoption in flexible and stretchable electronics. To achieve these goals, we consider blending a brittle donor-acceptor polymer, poly[4-(4,4 dihexadecyl-4H-cyclopenta[1,2-b:5,4-b']dithiophen-2-yl)-alt [1,2,5]thiadiazolo[3,4-c]pyridine] (PCDTPT), with ductile poly(3-hexylthiophene). We found that the ductility of the blend films is significantly improved compared to that of neat PCDTPT films, and when the blend film is employed in an OTFT, the performance is largely maintained. The ability to maintain charge transport character is due to vertical segregation within the blend, while the improved ductility is due to intermixing of the polymers throughout the film thickness. Importantly, the application of large strains to the ductile films is shown to orient both polymers, which further increases charge carrier mobility. These results highlight a processing approach to achieve high performance polymer OTFTs that are electrically and mechanically optimized. PMID- 27200459 TI - High Thermal and Electrical Conductivity of Template Fabricated P3HT/MWCNT Composite Nanofibers. AB - Nanoporous alumina membranes are filled with multiwalled carbon nanotubes (MWCNTs) and then poly(3-hexylthiophene-2,5-diyl) (P3HT) melt, resulting in nanofibers with nanoconfinement induced coalignment of both MWCNT and polymer chains. The simple sonication process proposed here can achieve vertically aligned arrays of P3HT/MWCNT composite nanofibers with 3 wt % to 55 wt % MWCNT content, measured using thermogravimetric methods. Electrical and thermal transport in the composite nanofibers improves drastically with increasing carbon nanotube content where nanofiber thermal conductivity peaks at 4.7 +/- 1.1 Wm( 1)K(-1) for 24 wt % MWCNT and electrical percolation occurs once 20 wt % MWCNT content is surpassed. This is the first report of the thermal conductivity of template fabricated composite nanofibers and the first proposed processing technique to enable template fabrication of composite nanofibers with high filler content and long aspect ratio fillers, where enhanced properties can also be realized on the macroscale due to vertical alignment of the nanofibers. These materials are interesting for thermal management applications due to their high thermal conductivity and temperature stability. PMID- 27200460 TI - Laparoscopic Treatment of Choledochal Cyst Using Barbed Sutures. AB - PURPOSE: The usage of barbed sutures is increasingly being reported in the field of laparoscopic surgery. However, there have been reports of suture-related complications such as small bowel obstruction or anastomosis stricture. We present our experience of hepaticojejunostomy (HJ) using V-loc, during laparoscopic cyst excision for choledochal cyst. METHODS: At our center, from August 2014 to January 2015, 4 patients were treated for choledochal cyst. Laparoscopic cyst excision with Roux-en-Y HJ was performed, and HJ was performed with intracorporeal suturing using unidirectional barbed sutures. After surgery, the patients were followed up in the outpatient clinic every 3 months to monitor for long-term complications such as biliary stricture. RESULTS: There were no short-term complications. Among the 4 patients, 3 patients did not experience any long-term complications. As of this writing, the follow-up period for the 4 patients is 16 months for the first 2 patients and 11 months for the later 2 patients. Biliary stricture was diagnosed in 1 patient at 7 month follow-up. HJ revision was performed with an open right subcostal incision. The anastomosis showed dense fibrosis and stricture. The patient recovered uneventfully after the surgery. CONCLUSIONS: HJ using barbed sutures was relatively easy to perform, but barbed sutures may have a tendency to cause stricture when used in biliary enteric anastomosis. Caution must be taken to prevent overtightening of the suture. PMID- 27200461 TI - Generation of Aspherical Optical Lenses via Arrested Spreading and Pinching of a Cross-Linkable Liquid. AB - Aspherical optical lenses with spatially varying curvature are desired for capturing high quality, aberration free images in numerous optical applications. Conventionally such lenses are prepared by multistep top-down processes which are expensive, time-consuming, and prone to high failure rate. In this context, an alternate method is presented here based on arrested spreading of a sessile drop of a transparent, cross-linkable polymeric liquid on a solid substrate heated to an elevated temperature. Whereas surface tension driven flow tends to render it spherical, rapid cross-linking arrests such flow so that nonequilibrium aspherical shapes are attained. It is possible to tune also the initial state of the drop via delayed pinching of a liquid cylinder which precedes its release on the substrate. This method has led to the generation of a wide variety of optical lenses, ranging from spherical plano convex to superspherical solid immersion to exotic lenses not achieved via conventional methods. PMID- 27200462 TI - Combining Psychodynamic Psychotherapy and Pharmacotherapy. AB - Many patients with depression, anxiety disorders, and other psychiatric disorders are treated with combinations of psychodynamic psychotherapy and medication. Whether this is better than monotherapy is an empirical question that requires much more extensive research than is currently available. When medications were first introduced to treat psychiatric illnesses, some psychopharmacologists insisted that it heralded a new area of "biological psychiatry" that would ultimately render psychotherapy obsolete. Psychodynamic theorists and practitioners, on the other hand, argued that psychopharmacology offered only a superficial approach to treatment. Fortunately, these battles are now largely supplanted by the belief that whatever treatment offers the patient the best outcome should be employed, regardless of the therapist's theoretical outlook. This should motivate more extensive study of the value of combination treatment. So far, the few studies that have been done suggest that the combination of psychodynamic psychotherapy and medication may be superior for the treatment of mood and anxiety disorders, but most of these studies have small sample sizes and involve only short-term psychotherapy. An examination of the neuroscience of mood and anxiety disorders and of the mechanism of action of psychodynamic psychotherapy and of antidepressant medication suggests several routes by which the two treatment modalities could be synergistic: stimulation of hippocampal neurogenesis; epigenetic regulation of gene expression; dendritic remodeling; enhanced prefrontal cortical control of limbic system activity; and action at specific neurohormonal and neurotransmitter targets. The evidence for each of these mechanisms is reviewed with an eye toward potential experiments that might be relevant to them. PMID- 27200463 TI - How Senior Psychodynamic Psychiatrists Regard Retirement. AB - The variety of personal experiences and attitudes about professional work among psychodynamic psychiatrists who have attained retirement age are explored through semi-structured interviews. Of 21 members of the American Academy of Psychoanalysis and Dynamic Psychiatry interviewed, 6 report fulltime engagement in professional activity, 10 partial reduction, and 5 full retirement from practice. Through direct quotations from the respondents' interviews several matters are considered including the concept of retirement, structural changes in practice, health concerns, dream experience, spirituality and matters of legacy, how others have influenced attitudes toward continued work, and how fears of retirement are manifest among those currently in practice. Among the conclusions is the suggestion that the sense of self-regard and personal satisfaction of those who do retire is far greater than anticipated by those still in active practice. PMID- 27200464 TI - On Beginnings and Endings: Reflections of an Early Career Psychiatrist and Psychoanalyst. PMID- 27200465 TI - The Emergence of Psychodynamic Psychotherapy for Treatment Resistant Patients: Intensive Short-Term Dynamic Psychotherapy. AB - Intensive short-term dynamic psychotherapy (ISTDP) was developed out of the need for relatively short psychodynamic psychotherapeutic treatment approaches to complex and resistant patient populations so common in public health systems. Based on extensive study of video recordings, Habib Davanloo discovered, and other researchers have validated, some important clinical ingredients that align the therapist with healthy aspects of the patient striving for resolution of chronic neurotic disorders and fragile character structure. In the case of character neurotic highly resistant patients, these approaches including "pressure," "clarification," "challenge to defenses," and "head on collision" can be used in a tailored and properly timed way to help the chronically suffering patient to overcome his or her own resistance and access core drivers of these pathologies. In this article the meta-psychological basis of ISTDP is reviewed and illustrated with an extended case vignette. PMID- 27200466 TI - Enactments in Psychoanalysis: Therapeutic Benefits. AB - The therapeutic benefits of enactments are addressed. Relevant literature reveals disparate conceptions about the nature and use of enactments. Clarification of the term is discussed. This analyst's theoretical and technical evolution is addressed; it is inextricably related to using enactments. How can it not be? A taxonomy of enactments is presented. The article considers that enactments may be fundamental in the evolution from orthodox to contemporary analytic technique. Assumptions underlying enactments are explored, as are guidelines for using enactments. Finally, the article posits that enactments have widened the scope of analysis and contributed to its vitality. PMID- 27200467 TI - A Cognitive-Developmental Model of Emotional Awareness and Its Application to the Practice of Psychotherapy. AB - The ability to be aware of one's own emotional states has been a time-honored ingredient of successful psychodynamic psychotherapy. With the rise of cognitive behavioral therapy (CBT), however, the utility of experiencing and reflecting upon emotional experience has become less certain, and a quantifiable measure of emotional awareness for clinicians has not been previously available. Several recent advances cast the role of emotional awareness in psychotherapy in a different light: (1) a new theory of change in psychotherapy has been formulated that highlights emotional experience as an important ingredient of change in a variety of modalities; (2) new evidence shows that individual differences in the capacity for emotional awareness predict successful psychotherapeutic outcome in the treatment of panic disorder both by manualized psychodynamic psychotherapy and CBT; and (3) a new online version of the electronic Levels of Emotional Awareness Scale (eLEAS) has been created that can be used with individual patients as a guide to psychotherapy treatment. Here we review evidence of a reliable and valid measure of emotional awareness that has been used in both normative and clinical contexts. The psychotherapeutic treatment of three patients is described to illustrate the clinical manifestations of the different levels of emotional awareness and the ways the eLEAS can be useful in the clinical context, including (1) assessment of the patient's current level of emotional functioning and his or her potential for higher levels of functioning, (2) the targeting of interventions to facilitate functioning at the next level, and (3) a possible marker of treatment progress. These observations suggest that the eLEAS has the potential to be a clinically useful tool that may assist clinicians in guiding psychotherapy treatment. PMID- 27200469 TI - Superhard Monoborides: Hardness Enhancement through Alloying in W1- x Tax B. AB - In tungsten monoboride (WB), the boron atoms are linked in parallel serpentine arrays, with tungsten atoms in between. This lattice is metallic, unlike conventional covalent superhard materials such as diamond or cubic boron nitride. By selectively substituting tungsten atoms with tantalum, the Vickers hardness can be increased to 42.8 GPa, creating a new superhard metal. PMID- 27200470 TI - International Data Sharing in Practice: New Technologies Meet Old Governance. AB - The social structures that govern data/sample release aim to safeguard the confidentiality and privacy of cohort research participants (without whom there would be no data or samples) and enable the realization of societal benefit through optimizing the scientific use of those cohorts. Within collaborations involving multiple cohorts and biobanks, however, the local, national, and supranational institutional and legal guidelines for research (which produce a multiplicity of data access governance structures and guidelines) risk impeding the very science that is the raison d'etre of these consortia. We present an ethnographic study, which examined the epistemic and nonepistemic values driving decisions about data access and their consequences in the context of the pilot of an integrated approach to co-analysis of data. We demonstrate how the potential analytic flexibility offered by this approach was lost under contemporary data access governance. We identify three dominant values: protecting the research participant, protecting the study, and protecting the researcher. These values were both supported by and juxtaposed against a "public good" argument, and each was used as a rationale to both promote and inhibit sharing of data. While protection of the research participants was central to access permissions, decisions were also attentive to the desire of researchers to see their efforts in building population biobanks and cohorts realized in the form of scientific outputs. We conclude that systems for governing and enabling data access in large consortia need to (1) protect disclosure of research participant information or identity, (2) ensure the specific expectations of research participants are met, (3) embody systems of review that are transparent and not compromised by the specific interests of one particular group of stakeholders, and (4) facilitate data access procedures that are timely and efficient. Practical solutions are urgently needed. New approaches to data access governance should be trialed (and formally evaluated) with input from and discussion with stakeholders. PMID- 27200471 TI - Inhibition of TNF-alpha, IL-1alpha, and IL-1beta by Pretreatment of Human Monocyte-Derived Macrophages with Menaquinone-7 and Cell Activation with TLR Agonists In Vitro. AB - Circulatory markers of low-grade inflammation such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1alpha), and interleukin-1 beta (IL-1beta) positively correlate with endothelial damage, atheroma formation, cardiovascular disease, and aging. The natural vitamin K2-menaquinone-7 (MK-7) added to the cell culture of human monocyte-derived macrophages (hMDMs) at the same time as toll like receptor (TLR) agonists did not influence the production of TNF-alpha. When the cells were pretreated up to 6 h with MK-7 before treatment with TLR agonists, MK-7 did not inhibit significantly the production of TNF-alpha after the TLR activation. However, 30 h pretreatment of hMDMs with at least 10 MUM of MK-7 effectively and dose dependently inhibited the proinflammatory function of hMDMs. Pretreatment of hMDMs with 10 MUM of MK-7 for 30 h resulted in 20% inhibition of TNF-alpha production after lipopolysaccharide (LPS) activation (P < .05) and 43% inhibition after macrophage-activating lipopeptide (MALP) activation (P < .001). Pathogen-associated molecular pattern (PMPP) activation was inhibited by 20% with MK-7 pretreatment; however, this inhibition was not statistically significant. The 30 h pretreatment of a THP-1-differentiated monocyte cell line with MK-7 resulted in a dose-dependent downregulation of TNFalpha, IL-1alpha, and IL-1beta gene expression as evaluated by RNA semiquantitative reverse transcription polymerase chain reaction (RT-PCR). MK-7 is able to modulate immune and inflammatory reactions in the dose-response inhibition of TNF-alpha, IL-1alpha, and IL-1beta gene expression and protein production by the healthy hMDMs in vitro. PMID- 27200472 TI - Simultaneous determination of lovastatin and its metabolite lovastatin acid in rat plasma using UPLC-MS/MS with positive/negative ion-switching electrospray ionization: Application to a pharmacokinetic study of lovastatin nanosuspension. AB - Lovastatin (LOV) is an antihyperlipidemic agent which exhibits low bioavailability due to its poor solubility. Therefore, a nanosuspension (NS) was developed as an efficient strategy to improve its oral bioavailability. To evaluate the pharmacokinetics of LOV-NS, a novel, sensitive, and rapid UPLC-MS/MS method was developed and validated for the simultaneous determination of LOV and its metabolite lovastatin acid (LOVA) in rat plasma. Simvastatin (IS) was chosen as the internal standard, and a liquid-liquid extraction method was used to isolate LOV and LOVA from biological matrices. The analytes were analyzed on an Acquity UPLC BEH C18 column, and a gradient program was applied at a flow rate of 0.2mL/min. Then, a tandem quadrupole mass spectrometer coupled with a positive/negative ion-switching electrospray ionization interface was employed to detect the analytes. Quantitation of the analytes was performed in the multiple reaction monitoring mode to monitor the transitions of m/z 427.1->325.0 for LOV and m/z 441.1->325.0 for IS in the positive ion mode and m/z 421.0->101.0 for LOVA in the negative ion mode, respectively. The method was validated over the concentration range 0.25-500ng/mL (r(2)>=0.99) for both LOV and LOVA. The intra day and inter-day precision (RSD%) of LOV and LOVA were less than 12.87% and the accuracy (RE%) was less than 5.22%. The average extraction recoveries were 90.1% and 91.9% for LOV and LOVA, and the matrix effects were found to be between 85% and 115%. The stability study showed that both analytes were stable during the experiment. Finally, this method has been successfully applied to a pharmacokinetic study in rats following a single oral dose of 10mg/kg LOV-NS. PMID- 27200473 TI - Source discrimination of drug residues in wastewater: The case of salbutamol. AB - Analytical methods used for pharmaceuticals and drugs of abuse in sewage play a fundamental role in wastewater-based epidemiology (WBE) studies. Here quantitative analysis of drug metabolites in raw wastewaters is used to determine consumption from general population. Its great advantage in public health studies is that it gives objective, real-time data about community use of chemicals, highlighting the relationship between environmental and human health. Within a WBE study on salbutamol use in a large population, we developed a procedure to distinguish human metabolic excretion from external source of contamination, possibly industrial, in wastewaters. Salbutamol is mainly excreted as the sulphate metabolite, which is rapidly hydrolyzed to the parent compound in the environment, so this is currently not detected. When a molecule is either excreted un-metabolized or its metabolites are unstable in the environment, studies can be completed by monitoring the parent compound. In this case it is mandatory to assess whether the drug in wastewater is present because of population use or because of a specific source of contamination, such as industrial manufacturing waste. Because commercial salbutamol mainly occurs as a racemic mixture and is stereoselective in the human metabolism, the enantiomeric relative fraction (EFrel) in wastewater samples should reflect excretion, being unbalanced towards one of two enantiomers, if the drug is of metabolic origin. The procedure described involves chiral analysis of the salbutamol enantiomers by liquid chromatography-tandem mass spectrometry (LC-MS-MS) and calculation of EFrel, to detect samples where external contamination occurs. Samples were collected daily between October and December 2013 from the Milano Nosedo wastewater treatment plant. Carbamazepine and atenolol were measured in the sewage collector, as "control" drugs. Salbutamol EFrel was highly consistent in all samples during this three-month period, but a limited number of samples had unexpectedly high concentrations where the EFrel was close to that observed of the un-metabolized, commercially available drug, supporting the idea of an external source of contamination, besides human metabolic excretion. Results showed that, when present, non-metabolic daily loads could be evaluated indicating an average of 4.12g/day of salbutamol extra load due to non-metabolic sources. The stereoselectivity in metabolism and enantiomeric ratio analysis appears to be a useful approach in WBE studies to identify different sources of drugs in the environment, when no metabolic products are present at useful analytical levels. PMID- 27200477 TI - A multidimension cloud model-based approach for water quality assessment. AB - Lakes are vitally important, because they perform a multitude of functions, such as water supply, recreation, fishing, and habitat. However, eutrophication limits the ability of lakes to perform these functions. In order to reduce eutrophication, the first step is its evaluation. The process of evaluation entails randomness and fuzziness which must therefore be incorporated. This study proposes an eutrophication evaluation method, named Multidimension Normal Cloud Model (MNCM). The model regards each evaluation factor as a one-dimension attribute of MNCM, chooses reasonable parameters and determines the weights of evaluation factors by entropy. Thus, all factors of MNCM belonging to each eutrophication level are generated and the final eutrophication level is determined by the certainty degree. MNCM is then used to evaluate eutrophication of 12 typical lakes and reservoirs in China and its results are compared with those of the reference method, one-dimension normal cloud model, related weighted nutrition state index method, scoring method, and fuzzy comprehensive evaluation method. Results of MNCM are found to be consistent with the actual water status; hence, MNCM can be an effective evaluation tool. With respect to the former one dimension normal cloud model, parameters of MNCM are improved without increasing its complexity. MNCM can directly determine the eutrophication level according to the degree of certainty and can determine the final degree of eutrophication; thus, it is more consistent with the complexity of water eutrophication evaluation. PMID- 27200478 TI - Spatiotemporal trends in ground-level ozone concentrations and metrics in France over the time period 1999-2012. AB - The hourly ozone (O3) data from 332 background monitoring stations, spread in France, were analyzed over the period 1999-2012 and short-term trends were calculated. In the current climate change context, the calculation of human health- and vegetation-relevant metrics, and of associated trends, provides a consistent method to establish proper and effective policies to reduce the adverse O3 effects. The generation of optimal O3 maps, for risk and exposure assessment, is challenging. To overcome this issue, starting from a set of stations, a hybrid regression-interpolation approach was proposed. Annual surface O3 metrics, O3 human health metrics (number of exceedances of daily maximum 8-h values greater than 60 ppb and SOMO35) and O3 vegetation impact metrics (AOT40 for vegetation and forests) were investigated at individual sites. Citizens are more exposed to high O3 levels in rural areas than people living in the cities. The annual mean concentrations decreased by -0.12ppbyear(-1) at rural stations, and the significant reduction at 67% of stations, particularly during the warm season, in the number of episodic high O3 concentrations (e.g. 98th percentile, 0.19ppbyear(-1)) can be associated with the substantial reductions in NOx and VOCs emissions in the EU-28 countries since the early 1990s Inversely, the O3 background level is rising at 76% of urban sites (+0.14ppbyear(-1)), particularly during the cold period. This rise can be attributed to increases in imported O3 by long-range transport and to a low O3 titration by NO due to the reduction in local NOx emissions. The decrease in health-related and vegetation-relevant O3 metrics, at almost all stations, is driven by decreases in regional photochemical O3 formation and in peak O3 concentrations. The short-term trends highlight that the threat to population and vegetation declined between 1999 and 2012 in France, demonstrating the success of European control strategies over the last 20 years. However, for all exposure metrics, the issue of non-attainment of the target value for O3 persists in comparison with the objectives of air quality directives. The region at highest O3 risk is the South-eastern France. This study contains new information on the i) spatial distribution of surface O3 concentration, ii) exceedances and iii) trends to define more suitable standards for human health and environmental protection in France. PMID- 27200479 TI - A direct method for e-cigarette aerosol sample collection. AB - E-cigarette use is increasing in populations around the world. Recent evidence has shown that the aerosol produced by e-cigarettes can contain a variety of toxicants. Published studies characterizing toxicants in e-cigarette aerosol have relied on filters, impingers or sorbent tubes, which are methods that require diluting or extracting the sample in a solution during collection. We have developed a collection system that directly condenses e-cigarette aerosol samples for chemical and toxicological analyses. The collection system consists of several cut pipette tips connected with short pieces of tubing. The pipette tip based collection system can be connected to a peristaltic pump, a vacuum pump, or directly to an e-cigarette user for the e-cigarette aerosol to flow through the system. The pipette tip-based system condenses the aerosol produced by the e cigarette and collects a liquid sample that is ready for analysis without the need of intermediate extraction solutions. We tested a total of 20 e-cigarettes from 5 different brands commercially available in Maryland. The pipette tip-based collection system condensed between 0.23 and 0.53mL of post-vaped e-liquid after 150 puffs. The proposed method is highly adaptable, can be used during field work and in experimental settings, and allows collecting aerosol samples from a wide variety of e-cigarette devices, yielding a condensate of the likely exact substance that is being delivered to the lungs. PMID- 27200482 TI - The Author File: Robert E. Campbell. PMID- 27200480 TI - Equine schlafen 11 restricts the production of equine infectious anemia virus via a codon usage-dependent mechanism. AB - Human schlafen11 is a novel restriction factor for HIV-1 based on bias regarding relative synonymous codon usage (RSCU). Here, we report the cloning of equine schlafen11 (eSLFN11) and the characteristics of its role in restricting the production of equine infectious anemia virus (EIAV), a retrovirus similar to HIV 1. Overexpression of eSLFN11 inhibited EIAV replication, whereas knockdown of endogenous eSLFN11 by siRNA enhanced the release of EIAV from its principal target cell. Notably, although eSLFN11 significantly suppressed expression of viral Gag protein and EIAV release into the culture medium, the levels of intracellular viral early gene proteins Tat and Rev and viral genomic RNA were unaffected. Coincidently, similar altered patterns of codon usage bias were observed for both the early and late genes of EIAV. Therefore, our data suggest that eSLFN11 restricts EIAV production by impairing viral mRNA translation via a mechanism that is similar to that employed by hSLFN11 for HIV-1. PMID- 27200481 TI - Colorectal cancer screening: Estimated future colonoscopy need and current volume and capacity. AB - BACKGROUND: In 2014, a national campaign was launched to increase colorectal cancer (CRC) screening rates in the United States to 80% by 2018; it is unknown whether there is sufficient colonoscopy capacity to reach this goal. This study estimated the number of colonoscopies needed to screen 80% of the eligible population with fecal immunochemical testing (FIT) or colonoscopy and determined whether there was sufficient colonoscopy capacity to meet the need. METHODS: The Microsimulation Screening Analysis-Colon model was used to simulate CRC screening test use in the United States (2014-2040); the implementation of a national screening program in 2014 with FIT or colonoscopy with 80% participation was assumed. The 2012 Survey of Endoscopic Capacity (SECAP) estimated the number of colonoscopies that were performed and the number that could be performed. RESULTS: If a national screening program started in 2014, by 2024, approximately 47 million FIT procedures and 5.1 million colonoscopies would be needed annually to screen the eligible population with a program using FIT as the primary screening test; approximately 11 to 13 million colonoscopies would be needed annually to screen the eligible population with a colonoscopy-only screening program. According to the SECAP survey, an estimated 15 million colonoscopies were performed in 2012, and an additional 10.5 million colonoscopies could be performed. CONCLUSIONS: The estimated colonoscopy capacity is sufficient to screen 80% of the eligible US population with FIT, colonoscopy, or a mix of tests. Future analyses should take into account the geographic distribution of colonoscopy capacity. Cancer 2016;122:2479-86. (c) 2016 American Cancer Society. PMID- 27200483 TI - Purification, characterization and allergenicity assessment of 26kDa protein, a major allergen from Cicer arietinum. AB - Chickpea (CP), a legume of the family Fabaceae, is an important nutrient-rich food providing protein, essential amino acids, vitamins, dietary fibre, and minerals. Unfortunately, several IgE-binding proteins in CP have been detected that are responsible for allergic manifestations in sensitized population. Therefore, the prevalence of CP induced allergy prompted us towards purification, characterization and allergenicity assessment of a major ~26kDa protein from chickpea crude protein extract (CP-CPE). Purification of CP 26kDa protein was done using a combination of fractionation and anion exchange chromatography. This protein was further characterized as "Chain A, crystal structure of a plant albumin" from Cicer arietinum with Mol wt 25.8kDa by Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Further, allergenic potential of purified 25.8kDa protein was assessed using in vivo and in vitro model. Purified protein showed IgE-binding capacity with sensitized BALB/c mice and CP allergic patient's sera. Enhanced levels of specific and total IgE, MCP-1, MCPT-1, myeloperoxidase, histamine, prostaglandin D2, and cysteinyl leukotriene were found in sera of mice treated with CP ~26kDa protein. Further, expressions of Th2 cytokines (i.e. IL-4, IL-5, IL-13), transcription factors (i.e. GATA-3, STAT-6, SOCS-3) and mast cell signaling proteins (Lyn, cFgr, Syk, PLC-gamma2, PI-3K, PKC) were also found increased at mRNA and protein levels in the intestines of mice treated with CP ~26kDa protein. In addition, enhanced release of beta-hexosaminidase, histamine, cysteinyl leukotriene and prostaglandin D2 were observed in RBL2H3 cell line when treated (125MUg) with CP 26kDa protein. Conclusively, in vivo and in vitro studies revealed the allergenic potential of purified CP 26kDa protein. Being a potential allergen, plant albumin may play a pivotal role in CP induced allergenicity. Current study will be helpful for better development of therapeutic approaches to prevent the allergenicity in CP sensitized individuals. PMID- 27200484 TI - 3DSEM++: Adaptive and intelligent 3D SEM surface reconstruction. AB - Structural analysis of microscopic objects is a longstanding topic in several scientific disciplines, such as biological, mechanical, and materials sciences. The scanning electron microscope (SEM), as a promising imaging equipment has been around for decades to determine the surface properties (e.g., compositions or geometries) of specimens by achieving increased magnification, contrast, and resolution greater than one nanometer. Whereas SEM micrographs still remain two dimensional (2D), many research and educational questions truly require knowledge and facts about their three-dimensional (3D) structures. 3D surface reconstruction from SEM images leads to remarkable understanding of microscopic surfaces, allowing informative and qualitative visualization of the samples being investigated. In this contribution, we integrate several computational technologies including machine learning, contrario methodology, and epipolar geometry to design and develop a novel and efficient method called 3DSEM++ for multi-view 3D SEM surface reconstruction in an adaptive and intelligent fashion. The experiments which have been performed on real and synthetic data assert the approach is able to reach a significant precision to both SEM extrinsic calibration and its 3D surface modeling. PMID- 27200485 TI - Positron backscattering from solid targets: Modeling of scattering processes via various approaches. AB - Monte Carlo simulation of 1-4keV positron backscattering from semi-infinite solid targets ranging from Be (z=4) to Au (z=79) with normal angle of incidence is here reported. In our study, the elastic and inelastic scattering cross sections are modeled by using various approaches based on either a classical or a quantum mechanical treatment. Calculations of positron backscattering coefficient are then reported for the solid targets of interest. The results obtained show a fairly good agreement with the data available in the literature. The dependence of the positron backscattering coefficient versus the atomic number of the solid target of interest has been investigated. In this respect, polynomial functions are proposed which does not require any recourse to Monte Carlo calculations. PMID- 27200486 TI - Influence of torso and arm positions on chest examinations by electrical impedance tomography. AB - Electrical impedance tomography (EIT) is increasingly used in patients suffering from respiratory disorders during pulmonary function testing (PFT). The EIT chest examinations often take place simultaneously to conventional PFT during which the patients involuntarily move in order to facilitate their breathing. Since the influence of torso and arm movements on EIT chest examinations is unknown, we studied this effect in 13 healthy subjects (37 +/- 4 years, mean age +/- SD) and 15 patients with obstructive lung diseases (72 +/- 8 years) during stable tidal breathing. We carried out the examinations in an upright sitting position with both arms adducted, in a leaning forward position and in an upright sitting position with consecutive right and left arm elevations. We analysed the differences in EIT-derived regional end-expiratory impedance values, tidal impedance variations and their spatial distributions during all successive study phases. Both the torso and the arm movements had a highly significant influence on the end-expiratory impedance values in the healthy subjects (p = 0.0054 and p < 0.0001, respectively) and the patients (p < 0.0001 in both cases). The global tidal impedance variation was affected by the torso, but not the arm movements in both study groups (p = 0.0447 and p = 0.0418, respectively). The spatial heterogeneity of the tidal ventilation distribution was slightly influenced by the alteration of the torso position only in the patients (p = 0.0391). The arm movements did not impact the ventilation distribution in either study group. In summary, the forward torso movement and the arms' abduction exert significant effects on the EIT waveforms during tidal breathing. We recommend strict adherence to the upright sitting position during PFT when EIT is used. PMID- 27200487 TI - The impact of langerin (CD207)+ dendritic cells and FOXP3+ Treg cells in the small bowel mucosa of children with celiac disease and atopic dermatitis in comparison to children with functional gastrointestinal disorders. AB - In the present study we aimed to evaluate the impact of langerin (CD207)+ dendritic cells (DCs) and FOXP3+ Treg cells in the intestinal mucosa of children with celiac disease (CD) and atopic dermatitis (AD) in comparison to children with functional gastrointestinal disorders (FGD). Seventy-five children (37 male, mean age 8.4 +/- 4.8 years), who randomly underwent small bowel biopsy, were studied. The CD was diagnosed in 14 children, including five persons with concomitant AD (all positive for anti-tissue transglutaminase IgA antibodies and with small bowel atrophy). Normal small bowel mucosa was found in eight patients with AD and in 53 patients with FGD. The sera of all patients were tested for total and specific IgE antibodies to food allergen panels. Staining for CD11c+, langerin (CD207+) DCs, CD4+, and FOXP3+ Treg cells was performed on paraffin embedded sections of bioptates using immunohistochemistry. The density of CD11c+ DCs, CD4+, and FOXP3+ Treg cells was higher in the CD patients compared to the AD and FGD patients (p = 0.02; p = 0.001). In AD, significantly higher density of CD11c+ DCs was detected in patients positive for specific IgE to food allergen panels (p = 0.02). The FGD patients with elevated total IgE had increased density of langerin (CD207)+ DCs compared to the patients with normal total IgE levels (p = 0.01). The increased density of FOXP3+ Treg cells, CD4+, cells and CD11c+ DCs was associated with CD but not with AD. The elevated level of total IgE or specific IgE to food allergens was associated with more pronounced expression of DCs, indicating a possible link between the presence of these cells in small bowel mucosa with elevated level of serum IgE. PMID- 27200488 TI - Elastic chitosan/chondroitin sulfate multilayer membranes. AB - Freestanding multilayered films were obtained using layer-by-layer (LbL) technology from the assembly of natural polyelectrolytes, namely chitosan (CHT) and chondroitin sulfate (CS). The morphology and the transparency of the membranes were evaluated. The influence of genipin (1 and 2 mg ml(-1)), a naturally-derived crosslinker agent, was also investigated in the control of the mechanical properties of the CHT/CS membranes. The water uptake ability can be tailored by changing the crosslinker concentration that also controls the Young's modulus and ultimate tensile strength. The maximum extension tends to decrease upon crosslinking with the highest genipin concentration, compromising the elastic properties of CHT/CS membranes: nevertheless, when using a lower genipin concentration, the ultimate tensile stress is similar to the non-crosslinked one, but exhibits a significantly higher modulus. Moreover, the crosslinked multilayer membranes exhibited shape memory properties, through a simple hydration action. The in vitro biological assays showed better L929 cell adhesion and proliferation when using the crosslinked membranes and confirmed the non-cytotoxicity of the developed CHT/CS membranes. Within this research work, we were able to construct freestanding biomimetic multilayer structures with tailored swelling, mechanical and biological properties that could find applicability in a variety of biomedical applications. PMID- 27200489 TI - Using metabolomics to dissect host-parasite interactions. AB - Protozoan parasites have evolved diverse growth and metabolic strategies for surviving and proliferating within different extracellular and intracellular niches in their mammalian hosts. Metabolomic approaches, including high coverage metabolite profiling and (13)C/(2)H-stable isotope labeling, are increasingly being used to identify parasite metabolic pathways that are important for survival and replication in vivo. These approaches are highlighting new links between parasite carbon metabolism and the ability of different parasite stages to colonize specific niches or host cell types. They have also revealed novel metabolic regulatory mechanisms that are important for homeostasis and survival in potentially nutrient variable environments. These studies highlight the importance of parasite and host metabolism as determinants of host-parasite interactions. PMID- 27200490 TI - Updating the definition of pain. PMID- 27200491 TI - Can immunostimulatory agents enhance the abscopal effect of radiotherapy? AB - Ionising radiation (IR) may harm cancer cells through a rare indirect out-of field phenomenon described as the abscopal effect. Increasing evidence demonstrates that radiotherapy could be capable of generating tumour-specific immune responses. On the other hand, effects of IR also include inhibitory immune signals on the tumour microenvironment. Following these observations, and in the context of newly available immunostimulatory agents in metastatic cancers (anti cytotoxic T lymphocyte-associated antigen 4 and programmed cell death protein-1 or -ligand 1 [PD1 or PDL-1]), there is a remarkable potential for synergistic combinations of IR with such agents that act through the reactivation of immune surveillance. Here, we present and discuss the pre-clinical and clinical rationale supporting the enhancement of the abscopal effect of IR on the blockade of immune checkpoints and discuss the evolving potential of immunoradiotherapy. PMID- 27200492 TI - When relative allocation depends on total resource acquisition: implication for the analysis of trade-offs. AB - A central tenet of evolutionary biology states that life-history traits are linked via trade-offs, as classically exemplified by the van Noordwijk and de Jong model. This model, however, assumes that the relative resource allocation to a biological function varies independently of the total resource acquisition. Based on current empirical evidence, we first explored the dependency between the total resource acquisition and the relative resource allocation to reproduction and showed that such dependency is the rule rather than the exception. We then derived the expression of the covariance between traits when the assumption of independence is relaxed and used simulations to quantify the importance of such dependency on the detection of trade-offs between current reproduction and future survival. We found that the dependency between the total energy acquisition and the relative allocation to reproduction can influence the probability to detect trade-offs between survival and reproduction. As a general rule, a negative dependency between the total energy acquisition and the relative allocation to reproduction should lead to a higher probability of detecting a trade-off in species with a fast pace of life, whereas a positive dependency should lead to a higher probability of detecting a trade-off in species with a slow pace of life. In addition to confirming the importance of resource variation to reveal trade offs, our finding demonstrates that the covariance between resource allocation and resource acquisition is generally not null and also plays a fundamental role in the detection of trade-offs. PMID- 27200493 TI - Red marrow and blood dosimetry in (131)I treatment of metastatic thyroid carcinoma: pre-treatment versus in-therapy results. AB - Treatment with radioiodine is a standard procedure for patients with well differentiated thyroid cancer, but the main approach to the therapy is still empiric, consisting of the administration of fixed activities. A predictive individualized dosimetric study may represent an important tool for physicians to determine the best activity to prescribe. The aim of this work is to compare red marrow and blood absorbed dose values obtained in the pre-treatment (PT) dosimetry phase with those obtained in the in-treatment (IT) dosimetry phase in order to estimate the predictive power of PT trial doses and to determine if they can be used as a decision-making tool to safely administer higher (131)I activity to potentially increase the efficacy of treatment. The PT and IT dosimetry for 50 patients has been evaluated using three different dosimetric approaches. In all three approaches blood and red marrow doses, are calculated as the sum of two components, the dose from (131)I activity in the blood and the dose from (131)I activity located in the remainder of the body (i.e. the blood and whole-body contributions to the total dose). PT and IT dose values to blood and red marrow appear to be well correlated irrespective of the dosimetric approach used. Linear regression analyses of PT and IT total doses, for blood and red marrow, and the whole-body contribution to these doses, showed consistent best fit slope and correlation coefficient values of approximately 0.9 and 0.6, respectively: analyses of the blood dose contribution to the total doses also yielded similar values for the best fit slope but with correlation coefficient values of approximately 0.4 reflecting the greater variance in these dose estimates. These findings suggest that pre-treatment red marrow dose assessments may represent an important tool to personalize metastatic thyroid cancer treatment, removing the constraints of a fixed activity approach and permitting potentially more effective higher (131)I activities to be safely used in-treatment. PMID- 27200495 TI - Responsivity to dyslexia training indexed by the N170 amplitude of the brain potential elicited by word reading. AB - The present study examined training effects in dyslexic children on reading fluency and the amplitude of N170, a negative brain-potential component elicited by letter and symbol strings. A group of 18 children with dyslexia in 3rd grade (9.05+/-0.46years old) was tested before and after following a letter-speech sound mapping training. A group of 20 third-grade typical readers (8.78+/ 0.35years old) performed a single time on the same brain potential task. The training was differentially effective in speeding up reading fluency in the dyslexic children. In some children, training had a beneficial effect on reading fluency ('improvers') while a training effect was absent in others ('non improvers'). Improvers at pre-training showed larger N170 amplitude to words compared to non-improvers. N170 amplitude decreased following training in improvers but not in non-improvers. But the N170 amplitude pattern in improvers continued to differ from the N170 amplitude pattern across hemispheres seen in typical readers. Finally, we observed a positive relation between the decrease in N170 amplitude and gains in reading fluency. Collectively, the results that emerged from the present study indicate the sensitivity of N170 amplitude to reading fluency and its potential as a predictor of reading fluency acquisition. PMID- 27200494 TI - Performance on a computerized neurocognitive battery in 22q11.2 deletion syndrome: A comparison between US and Israeli cohorts. AB - Increasingly, the effects of copy number variation (CNV) in the genome on brain function and behaviors are recognized as means to elucidate pathophysiology of psychiatric disorders. Such studies require large samples and we characterized the neurocognitive profile of two cohorts of individuals with 22q11.2 deletion syndrome (22q11DS), the most common CNV associated with schizophrenia, in an effort to harmonize phenotyping in multi-site global collaborations. The Penn Computerized Neurocognitive Battery (PCNB) was administered to individuals with 22q11DS in Philadelphia (PHL; n=155, aged 12-40) and Tel Aviv (TLV; n=59, aged 12 36). We examined effect sizes of performance differences between the cohorts and confirmed the factor structure of PCNB performance efficiency in the combined sample based on data from a large comparison community sample. The cohorts performed comparably with notable deficits in executive function, episodic memory and social cognition domains that were previously associated with abnormal neuroimaging findings in 22q11DS. In mixed model analysis, while there was a main effect for site for accuracy (number of correct response) and speed (time to correct response) independently, there were no main site effects for standardized efficiency (average of accuracy and speed). The fit of a structural model was excellent indicating that PCNB tests were related to the targeted cognitive domains. Thus, our results provide preliminary support for the use of the PCNB as an efficient tool for neurocognitive assessment in international 22q11DS collaborations. PMID- 27200496 TI - Epigallocatechin gallate sensitizes cisplatin-resistant oral cancer CAR cell apoptosis and autophagy through stimulating AKT/STAT3 pathway and suppressing multidrug resistance 1 signaling. AB - Epigallocatechin gallate (EGCG) is a green tea polyphenol that presents anticancer activities in multiple cancer cells, but no available report was addressed for the underling molecular mechanism of cytotoxic impacts on drug resistant oral squamous cell carcinoma cells. In the present study, the inhibitory effects of EGCG were experienced on cisplatin-resistant oral cancer CAR cells. EGCG inhibited cell viability in a time- and concentration-dependent manner by a sulforhodamine B (SRB) assay. EGCG induced CAR cell apoptosis and autophagy by 4',6-diamidino-2-phenylindole (DAPI) dye, acridine orange (AO) staining and green fluorescent protein (GFP)-tagged LC3B assay, respectively. EGCG also significantly enhanced caspase-9 and caspase-3 activities by caspase activity assay. EGCG markedly increased the protein levels of Bax, cleaved caspase-9, cleaved caspase-3, Atg5, Atg7, Atg12, Beclin-1, and LC3B-II, as well as significantly decreased the expression of Bcl-2, phosphorylated AKT (Ser473) and phosphorylation of STAT3 on Tyr705 by western blotting in CAR cells. Importantly, the protein and gene expression of multidrug resistance 1 (MDR1) were dose-dependently inhibited by EGCG. Overall, downregulation of MDR1 levels and alterations of AKT/STAT3 signaling contributed to EGCG-induced apoptosis and autophagy in CAR cells. Based on these results, EGCG has the potential for therapeutic effect on oral cancer and may be useful for long-term oral cancer prevention in the future. (c) 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 845-855, 2017. PMID- 27200497 TI - HLA-DQ antibodies: are they real? Are they relevant? Why so many? AB - PURPOSE OF REVIEW: Recent reports on donor-specific antibodies documented an overwhelming frequency of antibodies to one specific locus - human leukocyte antigen DQ (HLA-DQ). This article provides a short summary of clinical observations, a historic perspective to account for the late recognition of the role of HLA-DQ antibodies as well as potential explanations. RECENT FINDINGS: The basic understanding of the complexity of HLA-DQ molecules (antigens and antibodies) existed already 3-4 decades ago. However, only more recent advancements in molecular techniques as well as solid phase platforms, that allow for testing antibody specificities against individual HLA targets, provided state of-the-art tools that are also amenable to mass applications. Thus, the significance of the polymorphic nature of both polypeptide chains of the DQ molecule, DQalpha and DQbeta, is only now re-emerging. SUMMARY: HLA-DQ antibodies are real, relevant, and abundant. In order to achieve a clinically useful understanding of this phenomenon, HLA-DQ antigens and antibodies should be viewed at the level of the physiologic structure, as it appears on the cell surface, namely, one unit composed as DQalphabeta. Preliminary data demonstrated that such an approach is likely to lead to more equitable calculation of calculated panel reactive antibody, improving the accuracy of virtual crossmatch prediction, and increasing the likelihood of finding a compatible donor for the very highly sensitized patients. PMID- 27200498 TI - Clinically relevant interpretation of solid phase assays for HLA antibody. AB - PURPOSE OF REVIEW: Accurate and timely detection and characterization of human leukocyte antigen (HLA) antibodies are critical for pre-transplant and post transplant immunological risk assessment. Solid phase immunoassays have provided increased sensitivity and specificity, but test interpretation is not always straightforward. This review will discuss the result interpretation considering technical limitations; assessment of relative antibody strength; and the integration of data for risk stratification from complementary testing and the patient's immunological history. RECENT FINDINGS: Laboratory and clinical studies have provided insight into causes of test failures - false positive reactions because of antibodies to denatured HLA antigens and false negative reactions resulting from test interference and/or loss of native epitopes. Test modifications permit detection of complement-binding antibodies and determination of the IgG subclasses. The high degree of specificity of single antigen solid phase immunoassays has revealed the complexity and clinical relevance of antibodies to HLA-C, HLA-DQ, and HLA-DP antigens. Determination of antibody specificity for HLA epitopes enables identification of incompatible antigens not included in test kits. SUMMARY: Detection and characterization of HLA antibodies with solid phase immunoassays has led to increased understanding of the role of those antibodies in graft rejection, improved treatment of antibody-mediated rejection, and increased opportunities for transplantation. However, realization of these benefits requires careful and accurate interpretation of test results. PMID- 27200500 TI - Systematic review of self-management in patients with schizophrenia: psychometric assessment of tools, levels of self-management and associated factors. AB - AIMS: The aim of this study was to provide an overview of existing knowledge about self-management assessment tools used in patients with schizophrenia, and levels of self-management and associated factors in these patients. BACKGROUND: Self-management empowers patients with chronic conditions to manage their illness and psychosocial consequences. With respect to patients with schizophrenia, knowledge concerning self-management is scarce. A systematic review of existing literature focusing on self-management in these patients may contribute to further research programming and practice development. DESIGN: A systematic review of the literature. DATA SOURCES: A systematic literature search was conducted in March 2015 in Medline, Embase, PsycINFO and CINAHL. REVIEW METHODS: Twelve articles were included. Data were extracted and categorized following the objectives of this review: (1) self-management assessment tools and their psychometric properties; (2) level of self-management; and (3) factors associated with self-management in patients with schizophrenia. RESULTS: The PIH scale, the PAM-MH and the IMR scale were used to assess self-management. The overall psychometric quality of these instruments showed to be fair to poor. The level of self-management in patients with schizophrenia is comparable with other mental health conditions, higher than general population and lower than patients with physical health conditions. Several factors (e.g. sense of coherence, recovery and hope) were found to be associated. CONCLUSION: Further efforts are needed to increase the methodological quality of psychometric research on self-management assessment tools. More insight in the level of self-management and associated factors may enhance the development of future interventions. PMID- 27200499 TI - Optimization of saturation-recovery dynamic contrast-enhanced MRI acquisition protocol: monte carlo simulation approach demonstrated with gadolinium MR renography. AB - Dynamic contrast-enhanced (DCE) MRI is widely used for the measurement of tissue perfusion and to assess organ function. MR renography, which is acquired using a DCE sequence, can measure renal perfusion, filtration and concentrating ability. Optimization of the DCE acquisition protocol is important for the minimization of the error propagation from the acquired signals to the estimated parameters, thus improving the precision of the parameters. Critical to the optimization of contrast-enhanced T1 -weighted protocols is the balance of the T1 -shortening effect across the range of gadolinium (Gd) contrast concentration in the tissue of interest. In this study, we demonstrate a Monte Carlo simulation approach for the optimization of DCE MRI, in which a saturation-recovery T1 -weighted gradient echo sequence is simulated and the impact of injected dose (D) and time delay (TD, for saturation recovery) is tested. The results show that high D and/or high TD cause saturation of the peak arterial signals and lead to an overestimation of renal plasma flow (RPF) and glomerular filtration rate (GFR). However, the use of low TD (e.g. 100 ms) and low D leads to similar errors in RPF and GFR, because of the Rician bias in the pre-contrast arterial signals. Our patient study including 22 human subjects compared TD values of 100 and 300 ms after the injection of 4 mL of Gd contrast for MR renography. At TD = 100 ms, we computed an RPF value of 157.2 +/- 51.7 mL/min and a GFR of 33.3 +/- 11.6 mL/min. These results were all significantly higher than the parameter estimates at TD = 300 ms: RPF = 143.4 +/- 48.8 mL/min (p = 0.0006) and GFR = 30.2 +/- 11.5 mL/min (p = 0.0015). In conclusion, appropriate optimization of the DCE MRI protocol using simulation can effectively improve the precision and, potentially, the accuracy of the measured parameters. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27200501 TI - [Pd4(MU3-SbMe3)4(SbMe3)4]: A Pd(0) Tetrahedron with MU3-Bridging Trimethylantimony Ligands. AB - The palladium(II) chlorostibine complex [PdCl2(SbMe2Cl)2]2 has a dimeric structure in the solid state, stabilized by hyper-coordination at the Lewis amphoteric Sb centers. Reaction with 8 equiv of MeLi forms [Pd4(MU3 SbMe3)4(SbMe3)4], whose structure comprises a tetrahedral Pd(0) core with four terminal SbMe3 ligands and four MU3-SbMe3 ligands, one capping each triangular Pd3 face. Density functional theory calculations, supported by energy decomposition analysis and the natural orbitals for chemical valence scheme, highlight significant donor and acceptor orbital contributions to the bonding between both the terminal and the bridging SbMe3 ligands and the Pd4 core. PMID- 27200502 TI - Changing national guidelines is not enough: the impact of 1990 IOM recommendations on gestational weight gain among US women. AB - BACKGROUND AND OBJECTIVES: Gestational weight gain (GWG) is associated with both long- and short-term maternal and child health outcomes, particularly obesity. Targeting maternal nutrition through policies is a potentially powerful pathway to influence these outcomes. Yet prior research has often failed to evaluate national policies and guidelines that address maternal and child health. In 1990, the U.S. Institute of Medicine (IOM) released guidelines recommending different GWG thresholds based on women's pre-pregnancy body mass index (BMI), with the goal of improving infant birth weight. In this study, we employ quasi experimental methods to examine whether the release of the IOM guidelines led to changes in GWG among a diverse and nationally representative sample of women. METHODS: Our sample included female participants of the National Longitudinal Survey of Youth who self-reported GWG for pregnancies during 1979-2000 (n=7442 pregnancies to 4173 women). We compared GWG before and after the guidelines were released using difference-in-differences (DID) and regression discontinuity (RD) analyses. RESULTS: In DID analyses we found no reduction in GWG among overweight/obese women relative to normal/underweight women. Meanwhile, RD analyses demonstrated no changes in GWG by pre-pregnancy BMI for either overweight/obese or normal/underweight women. Results were similar for women regardless of educational attainment, race or parity. CONCLUSIONS: These findings suggest that national guidelines had no effect on weight gain among pregnant women. These results have implications for the implementation of policies targeting maternal and child health via dietary behaviors. PMID- 27200503 TI - Leptin administration in physiological or pharmacological doses does not alter circulating irisin levels in humans. AB - Leptin is an adipokine causing browning of adipose tissue, and it thus increases energy expenditure. The same is true for irisin. We studied whether exogenously administered metreleptin affects serum irisin concentrations in humans, which would suggest a direct interplay between leptin and irisin. We performed two studies: a dose-escalating 1-day-long study and a randomized placebo-controlled study. Study 1: 15 healthy, normal-weight and/or obese male and female individuals participated in three 1-day-long trials of metreleptin administration in the fed state. Metreleptin was administered once at physiological and pharmacological (0.01, 0.1 and 0.3 mg per kg body weight) doses. Study 2: 18 apparently healthy hypoleptinemic young women with hypoleptinemia and secondary amenorrhea took part in this study. Subjects received either metreleptin in replacement doses (0.08 and/or 0.12 mg kg(-1)) or placebo for 16 weeks. Blood samples were analyzed for leptin and irisin. We found no effect of metreleptin administration on irisin levels of subjects studied at either the fasting or the fed state either in the short or the long term. We provide evidence that leptin is not altering circulating irisin levels in humans. PMID- 27200504 TI - Moving to a personalized medicine approach to promote health across the weight spectrum. PMID- 27200506 TI - Capsaicinoids and energy balance: the next step. PMID- 27200505 TI - Recovery of brain structural abnormalities in morbidly obese patients after bariatric surgery. AB - BACKGROUND/OBJECTIVES: Obesity-related brain structural abnormalities have been reported extensively, and bariatric surgery (BS) is currently the most effective intervention to produce sustained weight reduction in overtly obese (OB) people. It is unknown whether BS can repair the brain circuitry abnormalities concomitantly with long-term weight loss. SUBJECTS/METHODS: In order to investigate whether BS promotes neuroplastic structural recovery in morbidly OB patients, we quantified fractional anisotropy (FA), mean diffusivity (MD) and gray (GM) and white (WM) matter densities in 15 morbidly OB patients and in 18 normal weight (NW) individuals. OB patients were studied at baseline and also 1 month after laparoscopic sleeve gastrectomy surgery. RESULTS: Two-sample t-test between OB (baseline) and NW groups showed decreased FA values, GM/WM densities and increased MD value in brain regions associated with food intake control (that is, caudate, orbitofrontal cortex, body and genu of corpus callosum) and cognitive-emotion regulation (that is, inferior frontal gyrus, hippocampus, insula, external capsule) (P<0.05, family-wise error correction). Paired t-test in the OB group between before and after surgery showed that BS generated partial neuroplastic structural recovery in the OB group, but the differences had relative less strength and smaller volume (P<0.001). CONCLUSIONS: This study provides the first anatomical evidence for BS-induced acute neuroplastic recovery that might in part mediate the long-term benefit of BS in weight reduction. It also highlights the importance of this line of gut-brain axis research employing the combined BS and neuroimaging model for identifying longitudinal changes in brain structure that correlated with obesity status. PMID- 27200508 TI - Effect of C8mimPF6 on miniemulsion polymerization for application in new latex coating products. AB - C8mimPF6, as a type of room temperature ionic liquid (RTIL) with non-volatility and a low melting point, may replace conventional coalescing agents in latex coatings, thus preventing volatile organic compound (VOC) emissions caused by coalescing agents. In this study, systematic investigations on the effect of various factors including initiator type, initiator concentration, temperature and C8mimPF6 concentration on the conversion of latex and droplet/particle size of a miniemulsion during polymerization have been conducted. The presence of C8mimPF6 has shown to have a marked effect on the reaction rate. Such an effect strongly depends on the type of initiator being used. For polymerization initiated by 2,2-azobis (isobutyronitrile) (AIBN), C8mimPF6 had a promoting effect on the reaction rate at low concentrations, but this effect might be reversed upon certain C8mimPF6 concentrations, e.g. 10 wt%. While initiated by H2O2/Vc, this promoting effect faded even at low C8mimPF6 concentrations. The different limiting factors, which determine the reaction rate with different types of initiator, may contribute to the results. For reactions initiated by hydrophobic AIBN, the reaction was dominated by kinetics. The presence of C8mimPF6 may cause an enhanced chain propagation rate and reduced chain termination rate, which may further contribute to the increase in reaction rate at lower concentrations of C8mimPF6. With hydrophilic H2O2/Vc, the resistance for the transfer of radicals into a droplet/particle might be increased significantly with increasing C8mimPF6 concentration due to a tighter interfacial structure at lower concentrations of C8mimPF6. Thus, such transfer of radicals may become a limiting step whilst the presence of C8mimPF6 increases the transfer resistance on radicals resulting in a decrease in reaction rate. The reaction temperature, which is related to the decomposition temperature of the initiator being used, was another factor affecting the conversion of latex and the size of latex particles. A higher temperature e.g. 50 degrees C promotes the coalescence of droplets/particles, and hence produces larger latex particles. In the presence of C8mimPF6, the reaction temperature could be significantly reduced to as low as 40 degrees C, which prevents phase separation. The final particle size depends on the nucleation mechanism as well as the coalescence of droplets/particles during polymerization. PMID- 27200507 TI - Obesity but not high-fat diet impairs lymphatic function. AB - BACKGROUND/OBJECTIVES: High-fat diet (HFD)-induced obesity has significant negative effects on lymphatic function, but it remains unclear whether this is a direct effect of HFD or secondary to adipose tissue deposition. METHODS: We compared the effects of HFD on obesity-prone and obesity-resistant mice and analyzed lymphatic function in vivo and in vitro. RESULTS: Only obesity-prone mice had impaired lymphatic function, increased perilymphatic inflammation and accumulation of lipid droplets surrounding their lymphatic endothelial cells (LECs). LECs isolated from obesity-prone mice, in contrast to obesity-resistant animals, had decreased expression of VEGFR-3 and Prox1. Exposure of LECs to a long-chain free fatty acid increased cellular apoptosis and decreased VEGFR-3 expression, while inhibition of intracellular inhibitors of VEGFR-3 signaling pathways increased cellular viability. CONCLUSIONS: Collectively, our studies suggest that HFD-induced obesity decreases lymphatic function by increasing perilymphatic inflammation and altering LEC gene expression. Reversal of diminished VEGFR-3 signaling may rescue this phenotype and improve lymphatic function. PMID- 27200509 TI - Hydrothermally Oxidized Single-Walled Carbon Nanotube Networks for High Volumetric Electrochemical Energy Storage. AB - Improving volumetric energy density is one of the major challenges in nanostructured carbon electrodes for electrochemical energy storage device applications. Herein, a simple hydrothermal oxidation process of single-walled carbon nanotube (SWNT) networks in dilute nitric acid is reported, enabling simultaneous physical densification and chemical functionalization of the as assembled randomly-packed SWNT films. After the hydrothermal oxidation process, the density of the SWNT films increases from 0.63 to 1.02 g cm(-3) and a considerable amount of redox-active oxygen functional groups are introduced on the surface of the SWNTs. The functionalized SWNT films are used as positive electrodes against Li metal negative electrodes for potential Li-ion capacitors or Li-ion battery applications. The functionalized SWNT electrodes deliver high volumetric as well as gravimetric capacities, 154 Ah L(-1) and 152 mAh g(-1) , respectively, owing to the surface redox reactions between the introduced oxygen functional groups and Li ions. In addition, these electrodes exhibit a remarkable rate-capability by retaining its high capacity of 94 Ah L(-1) (92 mAh g(-1) ) at a high discharge rate of 10 A g(-1) . These results demonstrate the simple hydrothermal oxidation process as an attractive strategy for improving the volumetric performance of nanostructured carbon electrodes. PMID- 27200510 TI - In vivo bioimpedance changes during haemorrhagic and ischaemic stroke in rats: towards 3D stroke imaging using electrical impedance tomography. AB - Electrical impedance tomography (EIT) could be used as a portable non-invasive means to image the development of ischaemic stroke or haemorrhage. The purpose of this study was to examine if this was possible using time difference imaging, in the anesthetised rat using 40 spring-loaded scalp electrodes with applied constant currents of 50-150 MUA at 2 kHz. Impedance changes in the largest 10% of electrode combinations were -12.8% +/- 12.0% over the first 10 min for haemorrhage and +46.1% +/- 37.2% over one hour for ischaemic stroke (mean +/- SD, n = 7 in each group). The volume of the pathologies, assessed by tissue section and histology post-mortem, was 12.6 MUl +/- 17.6 MUl and 12.6 MUl +/- 17.6 MUl for haemorrhage and ischaemia respectively. In time difference EIT images, there was a correspondence with the pathology in 3/7 cases of haemorrhage and none of the ischaemic strokes. Although the net impedance changes were physiologically reasonable and consistent with expectations from the literature, it was disappointing that it was not possible to obtain reliable EIT images. The reason for this are not clear, but probably include confounding effects of secondary ischaemia for haemorrhage and tissue and cerebrospinal fluid shifts for the stroke model. With this method, it does not appear that EIT with scalp electrodes is yet ready for clinical use. PMID- 27200512 TI - High-dose chemotherapy and autologous bone marrow or stem cell transplantation versus conventional chemotherapy for women with early poor prognosis breast cancer. AB - BACKGROUND: Overall survival rates are disappointing for women with early poor prognosis breast cancer. Autologous transplantation of bone marrow or peripheral stem cells (in which the woman is both donor and recipient) has been considered a promising technique because it permits use of much higher doses of chemotherapy. OBJECTIVES: To compare the effectiveness and safety of high-dose chemotherapy and autograft (either autologous bone marrow or stem cell transplantation) with conventional chemotherapy for women with early poor prognosis breast cancer. SEARCH METHODS: We searched the Cochrane Breast Cancer Group Specialised Register, MEDLINE (1966 to October 2015), EMBASE (1980 to October 2015), the World Health Organization's International Clinical Trials Registry Search Platform, and ClinicalTrials.gov on the 21 October 2015. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing high-dose chemotherapy and autograft (bone marrow transplant or stem cell rescue) versus chemotherapy without autograft for women with early poor prognosis breast cancer. DATA COLLECTION AND ANALYSIS: Two review authors selected RCTs, independently extracted data and assessed risks of bias. We combined data using a Mantel Haenszel fixed-effect model to calculate pooled risk ratios (RRs) and 95% confidence intervals (CIs). We assessed the quality of the evidence using GRADE methods. Outcomes were survival rates, toxicity and quality of life. MAIN RESULTS: We included 14 RCTs of 5600 women randomised to receive high-dose chemotherapy and autograft (bone marrow transplant or stem cell rescue) versus chemotherapy without autograft for women with early poor prognosis breast cancer. The studies were at low risk of bias in most areas.There is high-quality evidence that high-dose chemotherapy does not increase the likelihood of overall survival at any stage of follow-up (at three years: RR 1.02, 95% CI 0.95 to 1.10, 3 RCTs, 795 women, I2 = 56%; at five years: RR 1.00, 95% CI 0.96 to 1.04, 9 RCTs, 3948 women, I2 = 0%; at six years: RR 0.94, 95% CI 0.81 to 1.08, 1 RCT, 511 women; at eight years: RR1.17, 95% CI 0.95 to 1.43, 1 RCT, 344 women; at 12 years: RR 1.18, 95% CI 0.99 to 1.42, 1 RCT, 382 women).There is high-quality evidence that high dose chemotherapy improves the likelihood of event-free survival at three years (RR 1.19, 95% CI 1.06 to 1.34, 3 RCTs, 795 women, I2 = 56%) but this effect was no longer apparent at longer duration of follow-up (at five years: RR 1.04, 95% CI 0.99 to 1.09, 9 RCTs, 3948 women, I2 = 14%; at six years RR 1.04, 95% CI 0.87 to 1.24, 1 RCT, 511 women; at eight years: RR 1.27, 95% CI 0.99 to 1.64, 1 RCT, 344 women; at 12 years: RR 1.18, 95% CI 0.95 to 1.45, 1 RCT, 382 women).Treatment related deaths were much more frequent in the high-dose arm (RR 7.97, 95% CI 3.99 to 15.92, 14 RCTs, 5600 women, I2 = 12%, high-quality evidence) and non-fatal morbidity was also more common and more severe in the high-dose group. There was little or no difference between the groups in the incidence of second cancers at four to nine years' median follow-up (RR 1.25, 95% CI 0.90 to 1.73, 7 RCTs, 3423 women, I2 = 0%, high-quality evidence). Women in the high-dose group reported significantly worse quality-of-life scores immediately after treatment, but there were few statistically significant differences between the groups by one year.The primary studies were at low risk of bias in most areas, and the evidence was assessed using GRADE methods and rated as high quality for all comparisons. AUTHORS' CONCLUSIONS: There is high-quality evidence of increased treatment related mortality and little or no increase in survival by using high-dose chemotherapy with autograft for women with early poor prognosis breast cancer. PMID- 27200511 TI - The role of interventional sialendoscopy and intraductal steroid therapy in patients with recurrent sine causa sialadenitis: a prospective cross-sectional study. AB - OBJECTIVES: To verify the role of interventional sialendoscopy and steroidal ductal irrigation in patients with recurrent sialadenitis. DESIGN: A prospective, cross-sectional pilot study. SETTING: University of Milan. PARTICIPANTS: Fifty four patients with sine causa recurrent sialadenitis who underwent interventional sialendoscopy (group A, 36 patients) or interventional sialendoscopy followed by a intraductal steroidal irrigations (group B, 18 patients). MAIN OUTCOMES MEASURES: The number of episodes of sialadenitis three and 6 months before and after sialendoscopy, and their severity assessed by means of a 0-10 pain visual analogue scale. RESULTS: In the population as a whole, a significant post treatment reduction in the number of episodes of 30.7 +/- 5.5 after 3 months and 34.6 +/- 10.2 after 6 months (P < 0.001) and a significant reduction in pain visual analogue scale values of 4.7 +/- 0.4 after 6 months (P < 0.001) occurred. There was a statistically significant reduction in both parameters at the same time points in both treatment groups (P >= 0.001), with no significant between group difference in pain visual analogue scale values, an albeit non-significant trend in favour of group B in terms of the number of episodes 3 months after therapy that became significant after 6 months (11.0 +/- 9.9 versus 20.5 +/- 9.5; P = 0.05). CONCLUSIONS: Interventional sialendoscopy is effective for the treatment of recurrent sialadenitis; the addition of intraductal steroidal irrigations seems to increase its value in the medium term. Further studies of larger case series with longer follow-up are needed to establish the possibly primary role of steroid therapy in blocking inflammation. PMID- 27200513 TI - Magnetic cylindrical colloids at liquid interfaces exhibit non-volatile switching of their orientation in an external field. AB - We study the orientation of magnetic cylindrical particles adsorbed at a liquid interface in an external field using analytical theory and high resolution finite element simulations. Cylindrical particles are interesting since they possess multiple locally stable orientations at the liquid interface so that the orientational transitions induced by an external field will not disappear when the external field is removed, i.e., the switching effect is non-volatile. We show that, in the absence of an external field, as we reduce the aspect ratio alpha of the cylinders below a critical value (alphac~ 2) the particles undergo spontaneous symmetry breaking from a stable side-on state to one of two equivalent stable tilted states, similar to the spontaneous magnetisation of a ferromagnet going through the Curie point. By tuning both the aspect ratio and contact angle of the cylinders, we show that it is possible to engineer particles that have one, two, three or four locally stable orientations. We also find that the magnetic responses of cylinders with one or two stable states are similar to that of paramagnets and ferromagnets respectively, while the magnetic response of systems with three or four stable states are even more complex and have no analogs in simple magnetic systems. Magnetic cylinders at liquid interfaces therefore provide a facile method for creating switchable functional monolayers where we can use an external field to induce multiple non-volatile changes in particle orientation and self-assembled structure. PMID- 27200514 TI - Changes in Potassium Concentration During Opioid Antagonist Induction: Comparison of Two Randomized Clinical Trials. AB - OBJECTIVES: Opioid antagonist induction under general anesthesia or heavy sedation has been criticized due to its associated morbidity and mortality. Information on the potential causes of these complications is limited. We aimed to compare electrolyte concentration changes during rapid opioid antagonist induction under general anesthesia and conscious sedation, and to find out whether these changes are associated with cardiovascular complications. METHODS: We used a pooled database analysis of 2 prospective randomized controlled clinical trials carried out in Lithuania between 2002 and 2014. Opioid-dependent patients underwent opioid antagonist induction under general anesthesia (n = 50) or conscious sedation (n = 68). Electrolyte levels were measured before the procedure, 3 hours after antagonist induction, and 3 hours after the end of the procedure. RESULTS: General anesthesia was associated with initial hyperkalemia, which was followed by rapid reduction in potassium concentration (P < 0.01). Plasma potassium increase was noted in 92% of cases, and in 24%, these levels increased above 6.0 mmol/L, with a highest value of 6.7 mmol/L. Potassium concentration changes in the conscious sedation group were not statistically significant. There were no differences in sodium, calcium, chloride, and magnesium concentrations in both groups. CONCLUSIONS: Plasma potassium concentration changes in the general anesthesia group were significant, whereas conscious sedation had no effect on electrolyte levels. Our data support the recommendation of the American Society of Addiction Medicine and other professional societies that opioid antagonist induction under general anesthesia must not be offered. PMID- 27200515 TI - CLABSI Reduction Strategy: A Systematic Central Line Quality Improvement Initiative Integrating Line-Rounding Principles and a Team Approach. AB - BACKGROUND: Central line-associated bloodstream infections (CLABSIs) are the most common hospital-acquired infections costing hospitals millions of dollars annually. An evidence-based practice literature review revealed that utilizing a systematic team approach for proper line maintenance is effective in reducing CLABSI rates. PURPOSE: The purpose of this quality improvement initiative was to reduce the CLABSI rate in the neonatal intensive care unit from 3.9 per 1000 line days in 2011 by at least 50% in 2014. Policies, protocols, team members utilized, competencies, and techniques were created and a formal line-rounding and dressing change competency was established. The competency included specific criteria for performing daily line rounds and a 2-person sterile technique for dressing changes. FINDINGS/RESULTS: Central line-associated bloodstream infection rate was effectively reduced from 3.9 in 2011 to 0.3 per 1000 line days in 2014, with an overall 92% improvement. IMPLICATIONS FOR PRACTICE: Introduction of a dedicated CLABSI team has been shown to be effective in the reduction of CLABSI rates in the neonatal intensive care unit. IMPLICATIONS FOR RESEARCH: Further research is needed to evaluate how a team approach could be used to reduce other hospital acquired conditions; catheter-associated urinary tract infection, and hospital acquired pressure ulcers. PMID- 27200516 TI - Solitary rectal ulcer syndrome in a patient with anorexia nervosa: A case report. AB - This case report describes the clinical presentation, diagnosis, and management of a 26-year-old patient with anorexia nervosa (AN) diagnosed with Solitary Rectal Ulcer Syndrome (SRUS). To our knowledge, this is the first case report to document SRUS in AN, whose pathogenesis in this case seems to have been determined by the patient's malnourished and underweight state. Furthermore, SRUS symptoms appear to have interacted with the eating disorder psychopathology, increasing the need to exert control over eating. Cognitive behavioral strategies and procedures were accordingly used to address the eating disorder psychopathology and to promote complete weight restoration, which brought about a significant reduction in the size of the ulcer and the complete resolution of SRUS symptoms. (c) 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2016; 49:731 735). PMID- 27200517 TI - Opt-Out Referral of Men Who Have Sex With Men Newly Diagnosed With HIV to Partner Notification Officers: Results and Yield of Sexual Partners Being Contacted. AB - BACKGROUND: Given its potential for reducing the proportion of people with human immunodeficiency virus (HIV) unaware of their diagnosis, partner notification for HIV has been underutilized. This study aimed to determine if the implementation of opt-out referral of men who have sex with men, newly diagnosed with HIV, to partner notification officers (PNO) increased the proportion of sexual partners notified. METHODS: In April 2013, all individuals newly diagnosed with HIV at the Melbourne Sexual Health Centre, Australia were referred to Department of Health PNO to facilitate partner notification. The number of sexual partners reported by men and the proportion contacted in the 12 months before (opt-in period) and after (opt-out period) this policy change were determined through review of the clinical PNO records. RESULTS: Overall, 111 men were diagnosed with HIV during the study period. Compared with men in the opt-in period (n = 51), men in the opt out period (n = 60) were significantly more likely to accept assistance from the PNO (12 [24%] vs 51 [85%]; P < 0.001). A significantly higher proportion of reported partners were notified with opt-out referral (85/185, 45.9%; 95% confidence interval, 38.6-53.4) compared with opt-in referral (31/252, 12.3%; 95% confidence interval, 8.5-17.0) (P < 0.001). DISCUSSION: Opt-out referral to PNO was associated with a substantially higher proportion of partners at risk of HIV being contacted. PMID- 27200518 TI - Factors Associated With Recent Human Immunodeficiency Virus Testing Among Men Who Have Sex With Men in Puerto Rico, National Human Immunodeficiency Virus Behavioral Surveillance System, 2011. AB - BACKGROUND: Annual human immunodeficiency virus (HIV) testing is considered a key strategy for HIV prevention for men who have sex with men (MSM). In Puerto Rico, HIV research has primarily focused on injection drug use, yet male-to-male sexual transmission has been increasing in recent years. METHODS: Cross-sectional data from the National HIV Behavioral Surveillance system collected in 2011 in San Juan, Puerto Rico, were analyzed to identify factors associated with HIV testing in the past 12 months (recent testing). RESULTS: Overall, 50% of participants were tested recently. In the multivariate analysis, testing recently was associated with having multiple partners in the past 12 months (adjusted prevalence ratio [aPR] [>=4 vs 1 partner] = 1.5; 95% confidence interval [95% CI], 1.2-2.0), visiting a health care provider in the past 12 months (aPR, 1.4; 95% CI, 1.04-1.8), and disclosing male-male attraction/sex to a health care provider (aPR< 1.4; 95% CI, 1.1-1.7). CONCLUSIONS: Human immunodeficiency virus testing was suboptimal among MSM in San Juan. Strategies to increase HIV testing among MSM may include promoting HIV testing for all sexually active MSM including those with fewer partners, increasing utilization of the healthcare system, and improving patient-provider communication. PMID- 27200519 TI - The Effect of Human Immunodeficiency Virus Prevention and Reproductive Health Text Messages on Human Immunodeficiency Virus Testing Among Young Women in Rural Kenya: A Pilot Study. AB - BACKGROUND: More than half of human immunodeficiency virus (HIV)-infected individuals in Kenya are unaware of their status, and young women carry a disproportionate burden of incident HIV infections. We sought to determine the effect of an SMS intervention on uptake of HIV testing among female Kenyan college students. METHODS: We conducted a quasi-experimental study to increase HIV testing among women 18 to 24 years old. Four midlevel training colleges in Central Kenya were allocated to have their study participants receive either weekly SMS on HIV and reproductive health topics or no SMS. Monthly 9-question SMS surveys were sent to all participants for 6 months to collect data on HIV testing, sexual behavior, and HIV risk perception. We used multivariate Cox proportional hazards regression to detect differences in the time to the first HIV test reported by women during the study period. RESULTS: We enrolled 600 women between September 2013 and March 2014 of whom 300 received weekly SMS and monthly surveys and 300 received only monthly surveys. On average, women were 21 years of age (interquartile range, 20-22), 71.50% had ever had sex and 72.62% had never tested for HIV. A total of 356 women reported testing for HIV within the 6 months of follow-up: 67% from the intervention arm and 51% from the control arm (hazard ratio, 1.57; 95% confidence interval, 1.28-1.92). CONCLUSIONS: Use of weekly text messages about HIV prevention and reproductive health significantly increased rates of HIV testing among young Kenyan women and would be feasible to implement widely among school populations. PMID- 27200520 TI - Online Sex Partner Meeting Venues as a Risk Factor for Testing HIV Positive Among a Community-Based Sample of Black Men Who Have Sex With Men. AB - OBJECTIVES: In the United States, black men who have sex with men (BMSM) are disproportionately affected by the HIV epidemic. The elevated estimates of HIV among BMSM suggest that to slow rates of HIV infections, a range of factors that may contribute to transmission must be researched. Use of online venues for seeking out sex partners is one such area that may further advance our understanding of risks for HIV among BMSM. METHODS: Black men who have sex with men residing in Atlanta, GA, reporting HIV-negative/unknown status completed survey assessments and HIV antibody testing. Logistic regression using generalized linear modeling was used to conduct both bivariate and multivariable analyses of psychosocial variables-that is, substance use, sexually transmitted infection symptoms/diagnoses, sexual risk behavior, online sex partner meeting, and HIV test results. RESULTS: Two hundred thirty-two BMSM tested HIV negative and 39 BMSM tested HIV positive (14% new diagnoses). Reporting symptoms of a rectal sexually transmitted infection (odds ratio, 4.28; 95% confidence interval, 1.06-15.41) and use of sexual networking apps (odds ratio, 2.15; 95% confidence interval, 1.06-4.36) were both associated with testing HIV positive in a multivariable analysis. CONCLUSIONS: The use of sexual networking apps is associated with risks for HIV infection above and beyond what is captured by sexual risk behavior alone. Evaluating how sexual networking apps affect sexual networks and social norms regarding sexual risk taking and HIV transmission is an important and novel area for HIV prevention and intervention development. PMID- 27200521 TI - Did L Strains Responsible for Lymphogranuloma Venereum Proctitis Spread Among People With Genital Chlamydia trachomatis Infection in France in 2013? AB - We retrospectively analyzed 1802 nonrectal Chlamydia trachomatis-positive specimens to determine if the L strains responsible for rectal Lymphogranuloma venereum in men who have sex with men could spread to the heterosexual population. No evidence for Lymphogranuloma venereum transmission among heterosexuals in France was observed in 2013. L2b strains seem to be restricted to the men who have sex with men population. PMID- 27200522 TI - Population Excess Fraction of Ectopic Pregnancy Due to Chlamydia trachomatis in Finland. PMID- 27200523 TI - Increased Gonorrhea Screening and Case Finding After Implementation of Expanded Screening Criteria-Urban Indian Health Service Facility in Phoenix, Arizona, 2011 2013. AB - BACKGROUND: Gonorrhea screening is recommended for women at risk and men who have sex with men; expanded screening is encouraged based on local epidemiology. In response to a substantial increase in gonorrhea cases at an urban medical center serving American Indians, gonorrhea screening of all sexually active patients aged 14 to 45 years was initiated in March 2013. We describe gonorrhea screening coverage and case finding before and after implementation of expanded screening. METHODS: In March 2013, provider training, electronic health record prompts, and bundled laboratory orders were implemented to facilitate gonorrhea screening of all sexually active patients aged 14 to 45 years. We assessed the proportions of patients screened and testing positive for gonorrhea in the 2 years before (March 2011-February 2012 [indicated as 2011], March 2012-February 2013 [2012]) and 1 year after (March 2013-February 2014 [2013]) expanded screening measures. RESULTS: Gonorrhea screening coverage increased from 22% (2012) to 38% (2013); coverage increased 50% among females and 202% among males. Screening coverage increased in nearly all clinics. Gonorrhea case finding increased 68% among females in 2013 (n = 104) compared with 2012 (n = 62), primarily among women aged 25 to 29 years. No corresponding increase in gonorrhea case finding occurred among males. Most increased case finding occurred in the emergency department. CONCLUSIONS: After introduction of expanded gonorrhea screening, there was a significant increase in gonorrhea screening coverage and a subsequent increase in gonorrhea case finding among females. Despite increased screening in all clinics, increased case finding only occurred in the emergency department. PMID- 27200526 TI - Erratum: The heterogeneous energy landscape expression of KWW relaxation. PMID- 27200525 TI - Measures to improve microbial quality surveillance of gastrointestinal endoscopes. AB - BACKGROUND AND STUDY AIM: Infectious outbreaks associated with the use of gastrointestinal endoscopes have increased in line with the spread of highly resistant bacteria. The aim of this study was to determine the measures required to improve microbial quality surveillance of gastrointestinal endoscopes. METHODS: We reviewed the results of all microbiological surveillance testing of gastrointestinal endoscopes and automatic endoscope reprocessors (AERs) performed at Brest Teaching Hospital from 1 January 2008 to 1 June 2015. We analyzed the influence of the time of incubation on the rate of positive results using the Kaplan - Meier method. We also studied risk factors for gastrointestinal endoscope contamination using a multivariable logistic regression model. RESULTS: Over the study period, 1100 microbiological tests of gastrointestinal endoscopes (n = 762) and AERs (n = 338) were performed. A total of 264 endoscope tests (34.6 %) showed a level of contamination higher than the target. After 2 days of incubation, contamination was apparent in only 55.5 % of the endoscopes that were later shown to be contaminated (95 % confidence interval [CI] 49.2 - 61.8). Multivariable analysis showed that the use of storage cabinets for heat-sensitive endoscopes significantly reduced the risk of endoscope contamination (odds ratio [OR] 0.23, 95 %CI 0.09 - 0.54; P < 0.001) and that the use of endoscopes older than 4 years significantly increased this risk (OR >= 6 vs. < 2 years 2.92, 95 %CI 1.63 - 5.24; P < 0.001). CONCLUSIONS: Microbiological culture technique, mainly incubation duration, strongly influenced the results of endoscope sampling. Samples should be cultured for more than 2 days to improve the detection of contaminated endoscopes. Particular attention should be paid to endoscopes older than 2 years and to those that are not stored in storage cabinets for heat-sensitive endoscopes. PMID- 27200524 TI - Severity of endoscopically identified esophageal rings correlates with reduced esophageal distensibility in eosinophilic esophagitis. AB - BACKGROUND/AIMS: A grading system for the endoscopic features of eosinophilic esophagitis (EoE) has recently been validated. The EoE Endoscopic Reference Score (EREFS) incorporates both inflammatory and remodeling features of EoE. High resolution impedance planimetry using the functional luminal imaging probe (FLIP) is a technique for quantification of esophageal remodeling. The aim of this study was to evaluate the association between endoscopic severity with EREFS and esophageal distensibility as measured with the FLIP. METHODS: Upper gastrointestinal endoscopy with biopsies and FLIP were performed in 72 adults with EoE. Endoscopic features of edema, rings, exudates, furrows, and stricture were evaluated using the EREFS system. Esophageal distensibility metrics obtained by FLIP, including the distensibility slope and distensibility plateau, were compared with EREFS parameters. Bivariate associations between EREFS parameters and histologic eosinophil density were assessed. RESULTS: Higher ring scores were associated with a lower distensibility plateau (rs = -0.46; P < 0.0001). An association was found between severity of exudates and eosinophil density (rs = 0.27; P = 0.02), as well as between furrows and eosinophil density (rs = 0.49; P < 0.0001). Severity of exudates and furrows, and degree of eosinophilia were not associated with the distensibility parameters. CONCLUSIONS: Endoscopic assessment of ring severity can serve as a marker for esophageal remodeling and may be useful for food impaction risk stratification in EoE. Eosinophil count was not significantly associated with esophageal distensibility, consistent with previous reports of dissociation between inflammatory activity and fibrostenosis in EoE. Endoscopic inflammatory features show a weak correlation with histopathology but should not replace histologic indices of inflammation. PMID- 27200527 TI - Multiwalled carbon nanotube reinforced biomimetic bundled gel fibres. AB - This work describes the fabrication and characterization of hydroxypropyl cellulose (HPC)-based biomimetic bundled gel fibres. The bundled gel fibres were reinforced with multiwalled carbon nanotubes (MWCNTs). A phase-separated aqueous solution with MWCNT and HPC was transformed into a bundled fibrous structure after being injected into a co-flow microfluidic device and applying the sheath flow. The resulting MWCNT-bundled gel fibres consist of multiple parallel microfibres. The mechanical and electrical properties of MWCNT-bundled gel fibres were improved and their potential for tissue engineering applications as a cell scaffold was demonstrated. PMID- 27200528 TI - Long-Term Impact of the Dutch Colorectal Cancer Screening Programme on Cancer Incidence: Exploration of the Serrated Pathway. PMID- 27200529 TI - Early Stage Cost-Effectiveness Analysis of a Brca1-Like Test to Detect Triple Negative Breast Cancers Responsive to High Dose Alkylating Chemotherapy. PMID- 27200530 TI - The Cost of Costing Treatments Incorrectly: Errors in the Application of Drug Prices in Economic Models Due to Differing Patient Weights. PMID- 27200531 TI - Primary Treatments for Intermediate-Risk Prostate Cancer: a Cost-Effectiveness and Value-of-Information Analysis. PMID- 27200532 TI - The Evaluation of Economic Methods to Assess the Social Value of Medical Interventions for Ultra-Rare Disorders (URDS). PMID- 27200533 TI - Evaluating the Quality of Evidence from a Network Meta-Analysis. PMID- 27200534 TI - Value in the Making: Harvesting the Value of Complex Medical Innovations in Practice. PMID- 27200535 TI - Amending the Guide to Methods of Technology Appraisal at Nice to Incorporate two New Value Elements: Burden of Illness And Wider Societal Impact. PMID- 27200536 TI - Cost-Effectiveness (CE) of Imaging-Guided Strategies for the Diagnosis of Coronary Artery Disease (CAD): Results From the Evinci Study. PMID- 27200537 TI - The Value of Risk-Stratified Information in the National Lung Cancer Screening Trial. PMID- 27200538 TI - Diagnosing Anxiety Disorders in Primary Care: a Systematic Review and Meta Analysis. PMID- 27200539 TI - Determinants of Increasing the Likelihood for a Positive Drug Reimbursement Recommendation in Scotland. PMID- 27200540 TI - Biosimilars Versus Brands for Rheumatoid Arthritis: Eu5 Payers and Prescribers Place their Bets. PMID- 27200541 TI - Preferences for Prioritizing Patients with Rare Diseases: a Survey of the General Population in Sweden. PMID- 27200542 TI - Effect of Self-Monitoring of Blood Glucose on Glycemic Control, Clinical Outcomes, and Health Care Costs in Diabetic Patients Using Insulin: a Retrospective Analysis. PMID- 27200543 TI - Understanding the Payer Dilemma with Biosimilar Mabs: Striking the Right Balance Between Budget Needs and Patient Outcomes. PMID- 27200544 TI - Quasi-Monte Carlo Simulation and Variance Reduction Techniques Substantially Reduce Computational Requirements of Patient-Level Simulation Models: an Application to a Discrete Event Simulation Model. PMID- 27200545 TI - Transition Probability Estimation Using Repeated Sampling from a Fitted Mixed Model. PMID- 27200546 TI - Extrapolation of Trial-Based Survival Curves Using External Information. PMID- 27200547 TI - Economic orphans? the prevalence of child-specific utilities in nice appraisals for paediatric indications. PMID- 27200548 TI - Estimating Survival Data from Published Kaplan-Meier Curves: a Comparison of Methods. PMID- 27200549 TI - Cost-Utility of Cancer Therapies - the 'Cost' of Different Utility Generation Strategies. PMID- 27200550 TI - Do new cancer drugs offer good value for money? the perspective of oncologists, payers, patients, and general population. PMID- 27200551 TI - Reimbursement Decisions for Pharmaceuticals in Sweden: the Impact of Cost Effectiveness and Disease Severity. PMID- 27200552 TI - The Importance of Treatment Classifications that Account for Concomitant Treatments in the Context of a Network Meta-Analysis Comparing Pharmacological Treatments for Chronic Heart Failure. PMID- 27200554 TI - Incidence Description and Costs of Acute Heart Failure in the Netherlands. PMID- 27200553 TI - Work Productivity Loss and Indirect Costs Associated with New Cardiovascular Events in High-Risk Patients with Hyperlipidemia - Estimates from Population Based Register Data in Sweden. PMID- 27200555 TI - Health Utility in Patients Following Cardiovascular Events. PMID- 27200556 TI - Follow-UP Autoantibody Testing and Health Care Utilization Among Patients with (Sustained) Celiac Disease Activity in the Netherlands. PMID- 27200557 TI - Impact of Morbidity in Populations of North London Clinical Commissioning Groups on Patient Admission Rates and Gp Referrals. PMID- 27200558 TI - The Impact of Different Levels of Clinical Pharmacist Interventions on the Therapeutic Plan and Cost Saving. PMID- 27200559 TI - Exploring the Flaws in Clinical Data that Lead to Rejection of Nice Submissions. PMID- 27200560 TI - Adherence to Antiretroviral Therapy (Art) Among Adult Hiv Positive Patients in Volta Regional Hospital, Ghana. PMID- 27200561 TI - Assessing the Relationship Between Patient Compliance to Blood Glucose Monitoring and Health Related Quality of Life. PMID- 27200563 TI - Cost-Effectiveness of Real-Time Medication Monitoring in Children with Asthma. PMID- 27200562 TI - The Burden Associated with Non-Adherence in European Patients with Depression. PMID- 27200564 TI - Information Used in the Decision-Making Process Regarding Influenza Vaccination Policy: Perceptions of Stakeholders in France and the Netherlands. PMID- 27200565 TI - Nice's Proposed Value-Based Assessment of Health Technologies: Concerns of Inconsistent Consideration of Social Values. PMID- 27200566 TI - Survival or Mortality: Framing of the Risk Attribute in a Discrete Choice Experiment. PMID- 27200567 TI - Mapping from SF-6D to EQ-5D: Changes in Estimates Based on the Choice of Algorithm. PMID- 27200568 TI - Do health technology agencies accept methods for dealing with treatment switching? PMID- 27200569 TI - Predicting the Impact of Value-Based Assessment on Future Nice Appraisals. PMID- 27200570 TI - Investigating the Impact of Perspective on Weighting Qalys: a Discrete Choice Experiment. PMID- 27200571 TI - Elicitation of Health State Utilities Associated with Varying Severities of Flare in Systemic Lupus Erythematosus. PMID- 27200572 TI - Valuing EQ-5D-5L: Does the Ordering of the Health Dimensions Impact on Health State Valuations? PMID- 27200573 TI - The Impact of Discrimination, Victimization and Social Standing on Health-Related Quality of Life. PMID- 27200574 TI - Quality of Life Decrements after Stroke. PMID- 27200575 TI - Differences Between Hypothetical and Experience-Based Value Sets for Eq-5d: Implications for Decision Makers. PMID- 27200576 TI - Hipos-ER (Hypoglycemia in Portugal Observational Study - Emergency Room): Outcomes with Different Anti-Hyperglycemic Agents. PMID- 27200577 TI - Hipos-ER (Hypoglycemia in Portugal Observational Study - Emergency Room): Clinical Outcomes in the Emergency Room. PMID- 27200578 TI - Regional Assessment of Severe Hypoglycemic Coma Events in Finland. PMID- 27200579 TI - Hipos-ER (Hypoglycemia in Portugal Observational Study - Emergency Room): Clinical Outcomes in Admitted Patients. PMID- 27200580 TI - Comparative Efficacy and Safety of Empagliflozin with Other Anti-Diabetic Drugs for the Treatment of Patients with Type 2 Diabetes Mellitus Who are Failing Insulin. PMID- 27200581 TI - Glycemic, Lipid, and Blood Pressure Control Among Individuals with Type 2 Diabetes Mellitus in Saudi Arabia. PMID- 27200582 TI - A Systematic Review and Network Meta-Analysis Assessing the Effectiveness and Tolerability of Gliptins and Sulfonylureas as Monotherapy in Patients with Type 2 Diabetes Mellitus If Metformin is not Considered Appropriate. PMID- 27200583 TI - Assessing the Relationship between Improved Life Expectancy Due to Better Cardiovascular Risk Factor Management and the Likelihood of Microvascular Complications in Type 2 Diabetes Mellitus. PMID- 27200584 TI - Long-Term Modeling of Using Manually Coded and Autocoded Blood Glucose Meters in Diabetes Treatment. PMID- 27200585 TI - Comparative Efficacy and Safety of Empagliflozin with Other Oral Antidiabetic Drugs for the Second Line Treatment of Type 2 Diabetes Mellitus. PMID- 27200586 TI - Comparative Efficacy and Safety of Empagliflozin with Other Antidiabetic Drugs for the Third Line Treatment of Type 2 Diabetes Mellitus. PMID- 27200587 TI - Budget Impect Analysis. PMID- 27200588 TI - A Decision-Focused Mixed Treatment Comparison (MTC) of Alternative Dpp-4 Inhibitors (Dpp-4i's) Used in Combination With Metformin or a Sulfonylurea for the Treatment of Type 2 Diabetes Mellitus (T2DM). PMID- 27200589 TI - Identifying Consistent Inconsistency in Network Meta-Analyses - An Illustration In Type 2 Diabetes. PMID- 27200590 TI - The Efficacy and Effectiveness in HBA1C-Lowering is Dependent on Baseline Body Mass Index (BMI) for Sitagliptin but not Canagliflozin in the Treatment of Type 2 Diabetes Mellitus (T2DM). PMID- 27200591 TI - Treatment Maintenance Duration of Dual Therapy with Metformin and Sitagliptin in Type 2 Diabetes - Real-World Data From Odyssee Study. PMID- 27200592 TI - Assessing Consistency in a Network Meta-Analysis to Compare Once Weekly Dulaglutide Versus Other Glp-1 Receptor Agonists in Patients with Type 2 Diabetes. PMID- 27200593 TI - Efficacy and Safety of Dipeptidyl Peptidase-4 Inhibitors: Systematic Review and Meta-Analysis. PMID- 27200594 TI - New Meta-Analysis of Patient-Level Data on Efficacy And Hypoglycaemia with Insulin Glargine or Nph Insulin in Type 2 Diabetes Mellitus (T2DM) According to Concomitant Oral Therapy. PMID- 27200595 TI - Preventing the Progression to Type 2 Diabetes Mellitus in Adults at High Risk: A Systematic Review And Network Meta-Analysis of Lifestyle, Pharmacological and Surgical Interventions. PMID- 27200596 TI - Management of Type 2 Diabetes Mellitus Among Patients Attending a Primary Health Care Setting in Qatar: A Study on Medication Use Pattern and Clinical Outcomes. PMID- 27200597 TI - Progression of Physiological Parameters Over Time in Type 1 Diabetes Mellitus Patients in France. PMID- 27200598 TI - Epidemiology and Unmet Medical Need in Diabetes Mellitus Type 2 in Germany Results of a Literature Search. PMID- 27200599 TI - Uses of Electronic Patient Information Systems and National Registers - Implementation of the Clinical Practice Guideline and Evaluation of Costs and Use of Resources in Patients with Incident Type 2 Diabetes in Finland. PMID- 27200600 TI - Economic Impact of Combining Metformin with Dipeptidyl Peptidase Inhibitors In Diabetic Patients With Renal Failure. PMID- 27200601 TI - Recombinant Growth Hormone Therapy in Children with GH Deficiency: First Interventional Study in Armenia. PMID- 27200602 TI - Effectiveness, Safety and Patients' Subjective Feelings of Insulin Pen-Needle: A Systematic Review. PMID- 27200603 TI - Assessment of The Economic Value Of Dpp-4 Inhibitor Alogliptin Compared With Sitagliptin, Saxagliptin, And Linagliptin. PMID- 27200604 TI - Trend in Prevalence and Distribution of Diabetes Mellitus Type I and Type II in the Netherlands. PMID- 27200605 TI - Factors Associated with Hospitalization of Type 2 Diabetic Patients with Hypoglycemic Episodes Assisted at Emergency Departments. PMID- 27200607 TI - Budget Impact Analysis of Adding Dapaglifozin To The Therapy of Diabetes Mellitus Type 2 In Bulgaria. PMID- 27200606 TI - The Impact of Treatment of Thyreoid Disease in Pregnant Women to the Outcome of Giving Birth. PMID- 27200608 TI - Cost-Effectiveness Analysis of Autocoded and Manually Coded Blood Glucose Meters In Diabetes Treatment. PMID- 27200609 TI - Effect of Smoking Status on Health Care Costs In Patients With Type 2 Diabetes: A Retrospective Nested Case-Control Economic Study In Routine Clinical Practice. PMID- 27200610 TI - Association of Changes In Body Weight With Health Care Costs Among Patients With Newly-Diagnosed Type-2 Diabetes In Sweden. PMID- 27200611 TI - Benefit Of Positive Airway Pressure (Pap) Therapy In Sleep Apnoea (Sa) Patients With Type Ii Diabetes Mellitus (T2dm) In Germany: A Retrospective Comparative Cohort Analysis Based On A Statutory Health Insurance Database. PMID- 27200612 TI - Evaluation of Potential Waste Of Growth Hormone Across Available Growth Hormone Pen Devices And An Electronic Growth Hormone Delivery Device. PMID- 27200613 TI - Health Economic Impact of Bariatric Surgery Revisted: Structured Review of Literature and Health Technology Assessments. PMID- 27200615 TI - Estimation of Costs Associated With Stroke In Diabetic Patients in Madrid (Spain) Using A New Simulation Model. PMID- 27200614 TI - Direct Costs Of Diabetes Mellitus In Poland. PMID- 27200616 TI - Estimation of Costs Associated With Cardiovascular Complications of Diabetic Patients In Madrid (Spain) Using A New Simulation Model. PMID- 27200618 TI - Metformin in Combination With Dipeptidyl Peptidase-4 Inhibitors or Sulfonylureas in The Treatment of Type 2 Diabetes: Clinical And Economic Impact. PMID- 27200617 TI - ARE TOTAL HEALTH CARE EXPENDITURES IMPACTED BY A NEW DIABETES DIAGNOSTIC FACTOR: HBA1C? PMID- 27200619 TI - Cost and Burden Of Hypercholesterolemia In Portugal. PMID- 27200620 TI - Cost Of Diabetes Related Chronic Complication In South Korea 2011. PMID- 27200621 TI - Medical Expenditure for People With Diabetes in Urban Employee Basic Medical Insureance in Fujian. PMID- 27200622 TI - Patient-Level Estimates of Diabetic Complications on Direct Medical Cost. PMID- 27200623 TI - Key Cost Drivers Of Type 2 Diabetes Mellitus: an International Literature Review. PMID- 27200624 TI - Indirect Costs of Diabetes Mellitus (Dm) From the Perspective of The Social Insurance Institution (Zus) In Poland. PMID- 27200625 TI - How to Estimate The Cost Of Diabetes Based on Information From The French Health Insurance Database (Sniiram)? PMID- 27200626 TI - Comparison of the Economic Burden and Health care Utilizations of u. S. Veteran Patients Diagnosed with Type 2 Diabetes Mellitus. PMID- 27200627 TI - Direct Cost of Diffuse Toxic Goiter and Its Complications In Ukraine. PMID- 27200628 TI - Medical Expenditures Associated With Type 2 Diabetes Mellitus in Japan: A Large Claims Database Study. PMID- 27200629 TI - Health Care Costs in Patients With Type 2 Diabetes in Flanders Based on A Combination of Clinical And Health Insurance Data. PMID- 27200630 TI - Multimorbidity Pharmaceutical Cost of Diabetes Mellitus. PMID- 27200631 TI - Impact of Early Microbiologic Culture in the Economic Burden of Care for Patients With Infected Diabetic Foot Ulcers At A Model Of Secondary Level Imss' Hospitals in Mexico. PMID- 27200632 TI - Direct Costs of Diabetic Foot Ulcers in Russia. PMID- 27200633 TI - Health Economic Evaluation of Canagliflozin in the Treatment of Type 2 Diabetes Mellitus in Czech Republic. PMID- 27200634 TI - Health Economics Evaluation for Insulin Injection Pen-Needle with Different Lengths in Patients With Diabetes in China. PMID- 27200635 TI - Burden of Non-Adherence To Type 1 Diabetes Mellitus Therapeutic Guidelines In France. PMID- 27200636 TI - Cost-Effectiveness Analysis of Insulin Detemir Versus Insulin Neutral Protamine Hagedorn (Nph) In Patients With Type 1 Diabetes Mellitus In Spain. PMID- 27200637 TI - Short-Term Cost-Effectiveness Analysis of Insulin Detemir Versus Insulin Neutral Protamine Hagedorn (Nph) In Patients With Type 2 Diabetes Mellitus in Spain. PMID- 27200638 TI - The Impact of Long-Term Clinical Evidence on Cost-Effectiveness of Exenatide Once Weekly (Bydureon(r)) Versus Insulin Glargine for Patients With Type 2 Diabetes Mellitus (T2dm) From A Uk Nhs Perspective. PMID- 27200639 TI - Cost-Effectiveness-Analysis of The New-Born Screening in Austria. PMID- 27200640 TI - Dapagliflozin (Forxiga(r)) Versus Glipizide As Add-On Therapies In Type 2 Diabetes Mellitus (T2dm); An Update of The Cost-Effectiveness Based On Long-Term Clinical Evidence From Uk Nhs Perspective. PMID- 27200641 TI - Health Economic Evaluation of Canagliflozin in the Treatment of Type 2 Diabetes Mellitus in Portugal. PMID- 27200642 TI - The Cost-Effectiveness OF Canagliflozin (Cana) Versus Dapagliflozin (Dapa) In Patients With Type 2 Diabetes Mellitus (T2dm) With Inadequate Control On Metformin (Met) Monotherapy In The United Kingdom. PMID- 27200644 TI - Economic Assessment of Delaying Insulin Treatment Through The Use of Newer Anti Diabetic Agents, Dapagliflozin (Forxiga(r)) And Exenatide (Bydureon(r)), Both As Add-On To Metformin; A Cost-Effectiveness Analysis From A Uk Nhs Perspective. PMID- 27200643 TI - Health-Economic Comparison of Sensor-Augmented Pump With Low Glucose Suspend Versus Insulin Pump Alone For The Treatment of Hypo-Prone Type 1 Diabetes In Hungary. PMID- 27200645 TI - The Cost-Effectiveness of Exenatide Bid Versus Insulin Lispro Tid As Add-On Therapy to Titrated Insulin Glargine in Patients With Type 2 Diabetes - An Analysis From The Swedish Health Care Perspective. PMID- 27200646 TI - Health Economic Evaluation of Canagliflozin in the Treatment of Type 2 Diabetes Mellitus in France. PMID- 27200647 TI - Health Economic Evaluation of Canagliflozin In The Treatment of Type 2 Diabetes Mellitus In Slovakia. PMID- 27200649 TI - Health Economic Evaluation of Canagliflozin In The Treatment of Type 2 Diabetes Mellitus In Norway. PMID- 27200648 TI - Health-Economic Comparison of Sensor-Augmented Pump With Low Glucose Suspend Versus Insulin Pump Alone For The Treatment Of Hypo-Prone Type 1 Diabetes In Slovakia. PMID- 27200650 TI - The Cost-Effectiveness Of Canagliflozin Verse Liraglutide In Patients With Type 2 Diabetes (T2dm) Failing To Achieve Glycaemic Control On Metformin Monotherapy In Ireland. PMID- 27200651 TI - Is Canagliflozin Cost-Effective Compared to Sitagliptin Across Multiple Lines of Type 2 Diabetes Mellitus (T2dm) Therapy In Ireland? PMID- 27200652 TI - Cost-Effectiveness Analysis of Liraglutide Versus Sitagliptin or Exenatide in Patients With Inadequately Controlled Type 2 Diabetes On Oral Antidiabetic Drugs In Greece. PMID- 27200653 TI - Is a Home Based Video Teleconcultation Setup Cost Effective For Lowering Hba1c For Patients With Type-2 Diabetes Over A Six-Month Period? PMID- 27200654 TI - The Cost-Effectiveness of Canagliflozin Verse Insulin-Secretagogues (Sulphonylureas) or Insulin In Patients With Type 2 Diabetes Mellitus (T2dm) As An Add-On To Metformin In Ireland. PMID- 27200655 TI - Cost Effectiveness Evaluation of Canagliflozin In Combination With Metformin in the Treatment Of Type 2 Diabetes Mellitus In Poland. PMID- 27200657 TI - The Cost-Effectiveness of Canagliflozin Compared With Liraglutide in Patients With Type 2 Diabetes Inadequately Controlled With Metformin and Sulfonylurea In France. PMID- 27200656 TI - Cost-Effectiveness of Interventions Aimed at Decreasing The Number of Amputations Among Patients With Diabetes Mellitus. PMID- 27200658 TI - Layering Interventions for Type-2 Diabetes Prevention Using The Sphr Diabetes Model. PMID- 27200659 TI - Cost-Effectiveness of Dapagliflozin Versus Dpp-4 Inhibitors as Monotherapy in the Treatment of Type 2 Diabetes Mellitus From A Uk Health Care Perspective. PMID- 27200660 TI - Cost-Effectiveness of Dapagliflozin Compared To Dpp-4 Inhibitors as Triple Therapy In Combination With Metformin and A Sulphonylurea In The Treatment Of Type 2 Diabetes Mellitus From A Uk Health Care Perspective. PMID- 27200661 TI - Cost-Effectiveness of Saxagliptin Compared To Glp-1 Analogues As An Add-On To Insulin in the Treatment of Type 2 Diabetes Mellitus From A Uk Health Care Perspective. PMID- 27200662 TI - The Place of Dpp-4 Inhibitors in the Treatment Algorithm of Diabetes Type 2: A Systematic Review of Cost-Effectiveness Studies. PMID- 27200663 TI - Systematic Review of Economic Evaluations of Dipeptidyl Peptidase-4 Inhibitors for the Treatment of Type 2 Diabetes Mellitus. PMID- 27200664 TI - Projection of Long Term Health-Economic Benefits of Sensor Augmented Pump (Sap) Versus Pump Therapy Alone (Csii) In Type 1 Diabetes, A Uk Perspective. PMID- 27200665 TI - Projection of Long Term Health Economic Benefits of Sensor Augmented Pump (Sap) Versus Pump Therapy Alone (Csii) In Uncontrolled Type 1 Diabetes In France. PMID- 27200666 TI - Cost-Effectiveness of A Short Message Service (Sms) Intervention To Prevent Type 2 Diabetes Among Adults With Impaired Glucose Tolerance. PMID- 27200667 TI - Cost-Minimisation Analysis of Dapagliflozin Compared To Lixisenatide As An Add-On To Insulin In The Treatment of Type 2 Diabetes Mellitus From A Uk Health Care Perspective. PMID- 27200668 TI - Economic Evaluation of Lanreotide Autogel in the Management of Acromegaly in Greece. PMID- 27200669 TI - The Opportunity of Treating Type Ii Diabetes With Dpp4i: An Economic Evaluation Verse Conventional Treatment in the Italian Setting. PMID- 27200670 TI - Cost-Minimisation Analysis of Saxagliptin Compared to Sitagliptin And Linagliptin As Triple Therapy In Combination With Metformin And A Sulphonylurea In The Treatment Of Type 2 Diabetes Mellitus From A Uk Health Care Perspective. PMID- 27200672 TI - Cost-Effectiveness of Exenatide Twice Daily (Bid) Added To Basal Insulin Compared To A Bolus Insulin Add-On In Turkey. PMID- 27200671 TI - Cost-Effectiveness of Sitagliptin Versus Sulfonylurea As An Add-On Therapy To Metformin In Patients With Type 2 Diabetes In A Belgium Setting. PMID- 27200673 TI - Comparative Cost-Effectiveness Analysis of Adding Twice-Daily Exenatide To Insulin Glargine Versus Adding Insulin Lispro To Treat Type 2 Diabetes In Spain. PMID- 27200674 TI - Retrospective analysis of the economic burden among cushing's disease patients in the u. S. Medicaid program. PMID- 27200675 TI - The Cost-Effectiveness of Tolvaptan for the Treatment of Hyponatraemia Secondary To Syndrome Of Inappropriate Antidiuretic Hormone Secretion in Sweden. PMID- 27200676 TI - The Cost-Effectiveness Of Saxagliptin When Added To Metformin And Sulphonylurea In The Treatment Of Type 2 Diabetes Mellitus In Spain. PMID- 27200677 TI - The Cost-Effectiveness of Dapagliflozin In Combination With Insulin for the Treatment of Type 2 Diabetes Mellitus (T2dm) In Spain. PMID- 27200678 TI - The Potential Value of Ongoing Support In Type-1 Diabetes Mellitus With Dafneplus: Exploratory Pre-Trial Cost-Effectiveness Analysis On Proposed Trial End-Point Target For 12-Month Hba1c Improvement. PMID- 27200679 TI - Cost-Effectiveness of Empagliflozin (Jardiance(r)) 10 Mg And 25 Mg Administered As An Add-on To Metformin Compared To Other Sodium-Glucose Co-Transporter 2 Inhibitors (Sglt2is) for Patients With Type 2 Diabetes Mellitus (T2dm) In The UK. PMID- 27200680 TI - Cost Effectiveness Analysis of Flash Glucose Monitoring for Type 2 Diabetes Patients Receiving Insulin Treatment In The Uk. PMID- 27200681 TI - Examining The Role Of Insulin Pen Devices In Acute Care Settings: A Review And Analysis of Health Resource Utilization. PMID- 27200682 TI - Cost-Effectiveness of Empagliflozin (Jardiance(r)) 10 Mg And 25 Mg Administered As An Add-On To Metformin And Sulfonilurea (Met+Su) Compared To Other Sodium Glucose Co-Transporter 2 Inhibitors (Sglt2is) in Patients with Type 2 Diabetes Mellitus (T2dm) In The Uk. PMID- 27200683 TI - Cost Effectiveness Evaluation of Canagliflozin in Combination with Metformin and Sulfonylurea in Comparison To Nph Insulin in the Treatment of Type 2 Diabetes Mellitus In Poland. PMID- 27200684 TI - Absenteeism and Presenteeism in A Population of Patients with Diabetic Foot Ulcers in Poland. PMID- 27200685 TI - Cost Analysis of Severe Hypoglycemia in Treated Type 2 Diabetic Patients According to Anti-Hyperglycemic Agent Therapy. PMID- 27200686 TI - Hipos-Er (Hypoglycemia in Portugal Observational Study - Emergency Room): Costs And Health Care Resource Consumption Data. PMID- 27200687 TI - The Health Service and Economic Impact of Glucagon Rescue Administration During Severe Hypoglycemic Events. PMID- 27200688 TI - Epidemiology and Direct Health Care Costs of Diabetic Retinopathy: Results From a Population-Based Study. PMID- 27200689 TI - Costs of Hospitalization of Type 2 Diabetic Patients Associated with Severe Hypoglycemia. PMID- 27200690 TI - Evaluation of the Burden of Illness of u. S. Medicare Patients Diagnosed with Hyperpotassemia. PMID- 27200691 TI - Factors Associated With Discontinuation of Sulfonylurea Therapy In Type 2 Diabetes Patients Who Initiate Insulin. PMID- 27200692 TI - Impact of Hypoglycemia on Discontinuing or Down-Titrating Sulfonylurea Among Type 2 Diabetes Patients Without Insulin. PMID- 27200693 TI - Guideline Adherence and Control Of Diabetes Mellitus With Co-Morbidities in a Tertiary-Care Hospital in Malaysia. PMID- 27200694 TI - The Relationship Between Macular Edema and Health Outcomes Among Patients With Diabetes in Western Europe. PMID- 27200695 TI - The Burden of Severe Hypoglicaemias and Diabetes Ketoacidosis: A Population-Based Study. PMID- 27200696 TI - EQ-5D Scores In Patients Receiving Tolvaptan for the Treatment Of Hyponatraemia Secondary to the Syndrome of Inappropriate Antidiuretic Hormone Secretion. PMID- 27200697 TI - German Patients' Preferences for Attributes Of Type 2 Diabetes Medications. PMID- 27200698 TI - Patient Experience With The Single-Use Pen For Injection of Once Weekly Dulaglutide in Injection-Naive Patients With Type 2 Diabetes. PMID- 27200699 TI - Best Practices in Integrating Home Glucometer Measurements With Electronic Patient Reported Outcomes (Epro) In Clinical Trials. PMID- 27200700 TI - The Development of an Integrated Ecoa Solution To Improve The Quality of Data Capture In Diabetes Clinical Trials. PMID- 27200701 TI - Self-Reported Frequency and Impact of Non-Severe Hypoglycaemia in Insulin-Treated Adults in the UK. PMID- 27200702 TI - Patient-Reported Outcomes of Dipeptidyl Peptidase-4 Inhibitors: A Systematic Review. PMID- 27200703 TI - Patients' Preferences in Oral Diabetes Treatment: A Discrete Choice Experiment in Type2 Diabetes Mellitus. PMID- 27200704 TI - Assessment of Effect of Continuous Subcutaneous Insulin Infusion Treatment, Insulin Analog And Human Insulin of Children With Diabetes. PMID- 27200705 TI - Sagit(c): A Novel Clinician-Reported Outcome for Managing Acromegaly in Clinical Practice. PMID- 27200706 TI - Hye and me as Identical Currencies in Preference Studies? A Discrete-Choice Experiment in Type2 Diabetes Mellitus. PMID- 27200707 TI - Patient Preferences in Treatment of Diabetes Mellitus: A Systematic Review of Stated Preference Surveys. PMID- 27200709 TI - Health Related Quality of Life Outcomes (Hrqol) and Resource Use Associated With Type 2 Diabetes Patients Taking Steps To Lose Weight In 5 European Countries. PMID- 27200708 TI - Psychometric Evaluation of the Hypoglycaemia Perspectives Questionnaire in Patients With Type 2 Diabetes Mellitus. PMID- 27200710 TI - The Impact Of Daytime And Nocturnal Non-Severe Hypoglycaemic Events On People With Diabetes In Turkey. PMID- 27200711 TI - The Prevalence of Hypoglycemia and Its Impact on The Quality of Life of Type 2 Diabetes Mellitus Patients in Greece (The Hypo Study). PMID- 27200712 TI - Racial Disparities in Type 2 Diabetes Health Care Utilization in Medicaid Adults With Developmental Disabilities. PMID- 27200713 TI - Effect of A Pharmacy-Based Diabetes Management Program on Glycemic Control in an Inpatient General Medicine Population. PMID- 27200714 TI - Quality Of Life in Teenagers and Young Adolescent Patients With Diabetes Mellitus Type I With Insulin Pens Or Insulin Pumps In The Czech Republic. PMID- 27200715 TI - Evaluation of The Impact of Pharmaceutical Cognitive Service on Quality of Life in Diabetic Patients. PMID- 27200716 TI - Association of Hypoglycemia With Different Oral Antidiabetic Treatments and Its Impact on Quality of Life and Disease Control In Patients With Type 2 Diabetes Mellitus (The Hypo Study). PMID- 27200717 TI - Is the rule of halves applicable in Diabetes Type 2? Evidence from Greece. PMID- 27200718 TI - Physicians Estimation Regarding The Impact Of Recession on Patient Adherence To Treatment In Diabetes Type 2 In Greece. PMID- 27200719 TI - Compliance to Hemoglobin A1c Testing Recommendations Following Initial Diabetes Diagnosis. PMID- 27200720 TI - Cost-Effectiveness of Theintroduction of A National Adherence Program for Type 2 Diabetes In Hungary. PMID- 27200721 TI - Which Newly-Diagnosed Diabetics Should Receive Dietary Counseling Services? Estimating Individualized Treatment Allocations that Optimize cost-Effectiveness in Real-World Data. PMID- 27200723 TI - Chronic Care Management. PMID- 27200722 TI - A Comparative Analysis on The Reimbursement Status Of Sensor Augmented Pump Therapy in Turkey and Other Selected Countries. PMID- 27200724 TI - Type 2 Diabetes Treatment Patterns Across Europe. PMID- 27200725 TI - Prescription of Rosiglitazone and Pioglitazone Folowing Safety Warnings: A Comparative Analysis of Trends in Dispensing Patterns in Denmark and Germany From 2007 To 2013. PMID- 27200726 TI - Assessing The Medication Use Among Diabetic Patients With Comorbid Diseases. PMID- 27200727 TI - Exploring The Determinants of Endocrinologist Visits In France. PMID- 27200728 TI - Non-Adherence And Non-Persistence Related To Glp-1 Therapy In Patients With Diabetes Mellitus Type 2 (T2dm): Analysis of A Large German Claims-Based Dataset And Comparison To Oral Anti-Diabetics. PMID- 27200729 TI - Six Years Of Incretin-Based Agents in Diabetes 2nd Type Treatment in the Czech Republic: The Utilization And Expenditure. PMID- 27200730 TI - An Observational Cohort Study of Diabetes-Associated Secondary Health Care Utilisation in Patients With Type 2 Diabetes Prescribed Dual Combination Therapy With Oral Anti-Hyperglycaemic Agents in the UK. PMID- 27200731 TI - The Use of Real World Data in the Decision-Making Process: An Example Using Blood Glucose Test Strip Use In Patients With Type 2 Diabetes In Ireland. PMID- 27200732 TI - Cost of Severe Hypoglycaemia in Hospitalized Patients In Poland- Is It Financed and Reported in a Right Way? PMID- 27200734 TI - Payer's Perceptions of Glucagon Kits Aimed at Reducing Administration Complexity During Severe Hypoglycemic Events. PMID- 27200733 TI - Factors Associated With Weight Gain and Hypoglycaemia and The Impact Upon Hospitalisation in Type 2 Diabetes Patients Managed With Metformin Plus Sulphonylurea. PMID- 27200735 TI - Patient Specific Landscape of Information Technology Solutions for Diabetes Self Management. PMID- 27200736 TI - Quality of Diabetes Care Among Obese and Overweight Patients at Nhg Polyclinics. PMID- 27200737 TI - Using Modern Information Technology For Medical and Pharmaceutical Care Of Patients With Diabetes Mellitus In Ukraine. PMID- 27200738 TI - Data Sources of Disease Epidemiology in German Drug Reimbursement Dossiers: Case Study Of Diabetes Mellitus Type II. PMID- 27200739 TI - Examining the Economic Benefits of Lifestyle Intervention in Segments of A Prediabetic Population. PMID- 27200740 TI - Efficacy of The Automated Target Glucose Control: A Systematic Review. PMID- 27200741 TI - Comparison in Methods Between National Institute for Health And Care Excellence (Nice) Submissions For Sodium-Glucose Co-Transporter 2 Inhibitors (Sglt-2i). PMID- 27200742 TI - Treatment Patterns Among Type 2 Diabetes Mellitus Patients in Saudi Arabia. PMID- 27200743 TI - Usage of Self-Monitoring of Blood Glucose (Smbg) By Diabetes Therapy Type in India. PMID- 27200744 TI - The Comparison Of Clinical Impact Between Entecavir And Tenofovir In Chronic Hbv Infection. PMID- 27200745 TI - Adherence to Nice Guidance For Initiating Glp-1 Mimetics Among Patients With Type 2 Diabetes In Primary Care In England And Wales - An Evaluation Using The Clinical Practice Research Datalink (Cprd). PMID- 27200746 TI - Effectiveness Of Probiotics In Irritable Bowel Syndrome: A Systematic Review With Meta-Analysis. PMID- 27200747 TI - The Incidence Of Upper And Lower Gastrointestinal Complications: A Retrospective Study Using A Japanese Health Care Database. PMID- 27200748 TI - Establishment Of A Hepatitis C Virus (Hcv) Cohort In A Large Israeli Hmo. PMID- 27200749 TI - Associations Between Crohn's Disease Severity And Specific Socio-Demographic, Quality-Of-Life And Coping Factors. PMID- 27200750 TI - Development And External Validation Of A Risk Calculator For Predicting Anemia In Patients Treated With Triple Therapy (Tt) Containing Boceprevir (Boc), Pegylated Interferon And Ribavirin (Pr). PMID- 27200751 TI - Budget Impact Analysis Of Sofosbuvir For The Treatment Of Hepatitis C In The Veneto Region, Italy. PMID- 27200752 TI - Budget Impact Analysis Of Biosimilar Infliximab For The Treatment Of Crohn's Disease In Six Central Eastern European Countries. PMID- 27200753 TI - Proton Pump Inhibitors In South Africa: Role Of Branded Generics. PMID- 27200755 TI - Burden Of Hospitalizations Related To Chronic Hepatitis C In France: Evolution Between 2009 And 2012. PMID- 27200754 TI - Direct Treatment Costs Of Cirrhosis In The Brazilian Public Health Care System: A 2008-2012 Retrospecteve Analysis. PMID- 27200756 TI - Mean Annual Cost Of Patients Hospitalized For Chronic Hepatitis C In France: The Hepc-Lone Study. PMID- 27200757 TI - Direct Health Care Costs Associated With Opioid-Induced Constipation. PMID- 27200758 TI - Economic And Quality-Of-Life Burden Of Moderate-To-Severe Irritable Bowel Syndrome With Constipation (Ibs-C) In Spain: The Ibis-C Study. PMID- 27200759 TI - Hospitalization Costs Associated With Liver Cirrhosis. PMID- 27200760 TI - The Cost Of Irritable Bowel Syndrome (Ibs) In England. PMID- 27200761 TI - A Cost Of Care Model For Inflammatory Bowel Disease With A Uk Nhs Perspective. PMID- 27200762 TI - Economic Evaluation Of Various Strategies For Antiviral Therapy For Previously Treated Patients With Chronic Hcv Genotipe 1 Infection. PMID- 27200763 TI - Health Care Cost Associated To Constipation Predominant Irritable Bowel Syndrome In Spain. PMID- 27200764 TI - Lubiprostone In Chronic Idiopathic Constipation: A Cost-Effectiveness Analysis. PMID- 27200765 TI - Cost-Effectiveness Of Linaclotide: A Valuable Option In The Treatment Of Irritable Bowel Syndrome. PMID- 27200766 TI - Cost-Effectiveness Analysis Of A Personalized Therapy For Genotype 1, Naive, Chronic Hepatitis C Patients In Italy. PMID- 27200767 TI - Sofosbuvir For The Treatment Of Chronic Hepatitis C: A Comprehensive Cost Effectiveness Analysis Across Hcv Genotypes, Pretreatment Conditions And Hiv Co Infection. PMID- 27200768 TI - Cost-Effectiveness Analysis Of Antiviral Pharmacotherapies For Treatment Of Chronic Hepatitis C Virus Infection In Russia. PMID- 27200769 TI - Cost-Effectiveness Analysis Of Triple Therapy With Peginterferon, Ribavirin, And Boceprevir For The Treatment Of Chronic Hepatitis C Virus Genotype 1 With Severe Fibrosis Under "Real-Life" Conditions. PMID- 27200770 TI - The Cost Effectiveness Analysis Of The Oral Anti-Viral Treatments Alternatives For The Chronic Hepatitis B In Turkey. PMID- 27200771 TI - Cost-Effectiveness Of Everolimus Plus Reduced Tacrolimus In De Novo Liver Recipients In The Italian Setting. PMID- 27200772 TI - Cost-Utility Analysis Of Screening Strategies For Nonalcoholic Steatohepatitis. PMID- 27200773 TI - The Cost-Effectiveness Of Sofosbuvir And Ribavirin Treatment In Hcv-Infected Patients Listed For Liver Transplantation. PMID- 27200774 TI - Cost-Utility Analysis Of Sofosbuvir For Treatment Of Genotype2 Chronic Hepatitis C In Japan. PMID- 27200775 TI - Quality Of Life Of Diarrheal Children And Caregivers In Thailand. PMID- 27200776 TI - Adherence Rates For Peginterferon + Ribavirin Compared With Telaprevir + Peginterferon + Ribavirin In Medicaid And Commercial Patients Treated For Chronic Hepatitis C. PMID- 27200777 TI - Estimating The Cost Of Liver Transplantation In Patients Diagnosed With Chronic Hepatitis C And B In The Uk. PMID- 27200778 TI - Economic Evaluation Studies In Gastroenterology In Brazil: A Systematic Review. PMID- 27200779 TI - Cost-Utility Analysis Of Fidaxomicin Compared To Vancomycin In The Management Of Severe Clostridium Difficile Infection In Poland. PMID- 27200780 TI - Self-Reported Health Related Quality Of Life Of Hepatitis C Virus (Hcv) Genotype 1 Patients With And Without Comorbid Conditions. PMID- 27200781 TI - Translation And Cultural Adaptation Difficulties Encountered During Linguistic Validation Of The Bristol Stool Scale. PMID- 27200782 TI - A Comparison Between The Health-Related Quality Of Life Reported By The General Population And By Patients With Major Liver Diseases. PMID- 27200783 TI - Mapping May Cause Straining: The Inconsistent Relationship Between A Disease- Specific Questionnaire (Pac-Qol) And Eq-5d Mapping In Constipation. PMID- 27200784 TI - How Does Non-Malignant Opioid Induced Constipation (Oic) Impact Health State Utility? PMID- 27200785 TI - A Health Technology-Related Cost Description Concerning Italian Ibd Centres Dealing With Crohn's Disease Results From Sole Study. PMID- 27200786 TI - Utilization Of Total Parenteral Nutrition In A South Indian Tertiary Care Hospital. PMID- 27200787 TI - Impact Of Irritable Bowel Syndrome With Constipation On Work Productivity And Daily Activity Among Commercially Insured Patients In The United States. PMID- 27200788 TI - Should Cost-Effectiveness Analysis Include The Cost Of Consumption Activities? An Empirical Investigation. PMID- 27200789 TI - Diagnosis And Management Of Moderate-To-Severe Irritable Bowel Syndrome With Constipation (Ibs-C) In Spain: The Ibis-C Study. PMID- 27200790 TI - Real World Studies Using Japanese Administrative Databases: Chronic Hepatitis C Treatment Pattern And Resource Use. PMID- 27200791 TI - High Therapeutic Efficiency With Sofosbuvir For The Treatment Of Chronic Hepatitis C. PMID- 27200792 TI - Which Metric To Choose For Indirect Comparison Of Treatments When Multiple Comparisons Are Feasible: Lubiprostone Verse Prucalopride In Chronic Constipation. PMID- 27200793 TI - The Costs-Effectiveness Of Sofosbuvir Verse Standard Of Care (Soc) In Chronic Hepatitis C From A Belgian Reimbursement Perspective. PMID- 27200794 TI - Cohort Of Hcv Patients In Italy: Sizing And Treatments In A Sample Of Italian Hepatology Centers. PMID- 27200795 TI - Comparison Of The Burden Of Ibs With Constipation On Health-Related Quality Of Life (Hrqol), Work Productivity, And Health Care Utilization To Asthma, Migraine, And Rheumatoid Arthritis In The Us, Uk, And France. PMID- 27200796 TI - Assesment Of Serial Transverse Enteroplasty: Systematic Review. PMID- 27200797 TI - Prescribing Pattern Of Drugs For Ulcerative Colitis In Japan. PMID- 27200798 TI - Patients Diagnostic Therapeutic Pathways For Hcv Patients In Italy: Impact Of Regionalization In Treatments And Guidelines. PMID- 27200799 TI - Claims Database Analysis Of Patients With Chronic Hepatitis C In Japan. PMID- 27200800 TI - Impact of Apremilast on Physical Function over 52 weeks in Patients with Active Psoriatic Arthritis. PMID- 27200801 TI - Work Productivity Improvement Associated With Apremilast, An Oral Phosphodiesterase 4 Inhibitor, in Patients With Psoriatic Arthritis Results Of A Phase 3, Randomized, Controlled Trial. PMID- 27200802 TI - Network Meta-Analysis With Baseline Risk Adjustment To Assess The Relative Efficacy Of Ustekinumab In Adult Patients With Active Psoriatic Arthritis. PMID- 27200803 TI - Comparison Of Disease Status And Outcomes Of Patients With Psoriatic Arthritis (Psa) Receiving Adalimumab Or Etanercept Monotherapy In Europe. PMID- 27200804 TI - Relative Efficacy And Safety of Ustekinumab Compared to Anti-TNF-Alfa Therapies in Patients With Active Psoriatic Arthritis. PMID- 27200805 TI - Drug Usage Analysis and Health Care Resources Consumption in Patients With Rheumatoid Arthritis. PMID- 27200806 TI - Comparative Effectiveness of Biological Agents With Diseases Modifying Anti Rheumatic Drugs For Methotrexate Failure Rheumatoid Arthritis Patients: A Baysian Mixed Treatment Comparison. PMID- 27200807 TI - Heal Rate In 4,190 Fresh Fractures Treated With Low-Intensity Pulsed Ultrasound (Lipus). PMID- 27200808 TI - Quality Of Life Assessments In Korean Patients With Rheumatoid Arthritis (Ra): An Analysis From The Phase Iii Trial To Evaluate Equivalence Of The Etanercept Biosimilar Hd203 And Enbrel(r) In Combination With Methotrexate (Mtx) In Patients With Ra; The Hera Study. PMID- 27200810 TI - Efficacy Of Novel Dmards In Early Active Rheumatoid Arthritis: An Indirect Comparison. PMID- 27200809 TI - Comparison of Disease Status And Outcomes of Patients With Rheumatoid Arthritis (Ra) Receiving Adalimumab or Etanercept Monotherapy In Europe. PMID- 27200811 TI - Using Health Assessment Questionnaire - Disability Index To Estimate Eq-5d Utility Values for Patients With Rheumatoid Arthritis in Taiwan. PMID- 27200813 TI - Pain Therapy for Osteoarthritis in Germany: Analysis of Sickness Fund Claims Data. PMID- 27200812 TI - Mast (Minimal Access Spinal Technologies) Versus Open Surgery: Cost Analysis From Hospital Perspective. PMID- 27200814 TI - A Budget Impact Analysis of Ustekinumab in the Management of Psoriatic Arthritis in Greece. PMID- 27200815 TI - Pharmacoeconomic Evaluation of Biologic Therapies in Russian Patients With Rheumatoid Arthritis and Intolerance or Inadequate Response to Conventional Basic Therap. PMID- 27200816 TI - Budget Impact Analysis of Certolizumab Pegol in the Management of Patients With Moderate-To-Severe Active Rheumatoid Arthritis in Greece. PMID- 27200817 TI - Current and Future Costs of Osteoporotic Fractures in the Netherlands. PMID- 27200819 TI - Direct Non-Medical Costs Of Rheumatoid Arthritis By Disease Level In Portugal. PMID- 27200818 TI - Claims Data Analysis on the Annual Frequency and Incremental Cost of Reoperations in Instrumental Spinal Surgeries in Germany. PMID- 27200820 TI - Cost Per Responder Of Apremilast Versus Etanercept And Adalimumab In Patients With Active Psoriatic Arthritis. PMID- 27200821 TI - Burden Of Disease Analysis Of Ankylosing Spondylitis In Hungary. PMID- 27200822 TI - Cost Comparison of Surgical and Non-Surgical Treated Lumbar Spinal Stenosis Patients. PMID- 27200823 TI - Burden of Disease Analysis of Psoriatic Arthritis In Hungary. PMID- 27200825 TI - Economic Modeling of The Use of Botulinum Toxin A in A Homogenous Patient Population Based on Real-Life Clinical Practice: Ulis-Ii (The Upper Limb International Spasticity Study). PMID- 27200824 TI - Early Retirement Indirect Costs Attributable to Rheumatic Diseases in Portugal. PMID- 27200826 TI - The Pension Costs of Musculoskeletal Diseases. Estimation of the Economic Burden Borne by the Italian Social Security System. PMID- 27200827 TI - The Costs of Diagnosis and Treatment of Ankle Sprains and Fractures, 1980-2013: A Systematic Review. PMID- 27200828 TI - Hospitalization Burden Among Dialysis Patients In Brazil: an Analysis of The Public Health System Database. PMID- 27200829 TI - Systematic Review of Societal Cost of Illness Evidence in Patients With Psoriatic Arthritis. PMID- 27200830 TI - Systematic Review of Societal Cost of Illness Evidence in Patients With Ankylosing Spondylitis. PMID- 27200831 TI - Determination Of The Annual Health Insurance Cost Of Outpatient Care Physiotherapy Services For Low Back Pain. PMID- 27200832 TI - Cost of Treating Hip Fractures With Cephalomedullary Nails: A Retrospective Claims Database Review. PMID- 27200833 TI - Cost Related to the Waiting List of Patients With Vertebral Malformation. PMID- 27200834 TI - Treating to the Target of Das28 < 2.6 in Rheumatoid Arthritis: the Impact of Efficacy on Cost Effectiveness. PMID- 27200835 TI - Cost-Effectiveness of Certolizumab Pegol in the Treatment of Active Rheumatoid Arthritis, Axial Spondyloarthritis, and Psoriatic Arthritis In Romania. PMID- 27200836 TI - Cost-Effectiveness of Celecoxib and Non Selective Non Steroidal Anti-Inflammatory Drug (Nsaid) Therapy for the Treatment of Osteoarthritis in Spain: A Decision Tree Model. PMID- 27200837 TI - Cost-Effectiveness Of Routine Testing For Hla-B*5801 In Caucasian Patients Newly Diagnosed With Gout In Portuguese Nhs Hospitals. PMID- 27200838 TI - Cost-Effectiveness Analysis of Tocilizumab Verse Infliximab for the Patients With Rheumatoid Arthritis in Kazakhstan. PMID- 27200839 TI - Estimating the Cost-Effective Intervention Thresholds for Osteoporotic Fractures Based on Frax(r) in the Greek Setting. PMID- 27200841 TI - Pharmacoeconomic Evaluation of Treatment With Tocilizumab in Russian Children With Systemic Juvenile Idiopathic Arthritis. PMID- 27200840 TI - The Cost-Effectiveness of Biologic Dmards in Patients With Severe or Mild-To Severe Rheumatoid Arthritis After Conventional Dmards. PMID- 27200842 TI - Health Economic Evaluation of Osteoporosis Screening and Treatment Strategy in the Elderly Japanese Women. PMID- 27200843 TI - Cost-Effectiveness of Use of Barricaid(r) In Lumbar Discectomy Surgery in Turkey. PMID- 27200844 TI - A Cost-Effectiveness Analysis for Total Knee Arthroplasty Telerehabilitation: Proof of Concept of A Decision Model. PMID- 27200845 TI - Cost-Effectiveness Analysis of Etanercept in the Treatment of Rheumatoid Arthritis In Portugal. PMID- 27200846 TI - The Impact of Disease Modification on the Cost-Effectiveness of Pegloticase for the Treatment of Severe Debilitating Chronic Tophaceous Gout In Adult Patients. PMID- 27200847 TI - Pharmacoeconomic Analysis Tofacitinib Use in Rheumatoid Arthritis Treatment Scheme. PMID- 27200848 TI - Rehabilitation In Resurfacing Hip Arthroplasty Patients: Preliminary Cost Effectiveness Results From A Clinical Trial. PMID- 27200849 TI - Cost-Effectiveness Model of Dual-Mobility Cups for Total Hip Replacement in France. PMID- 27200850 TI - Comparison of Diagnostic Strategies to Detect Prevalent Vertebral Fracture for Adults Over Age 50: Use of Vertebral Fracture Assessment or Spine Radiography. PMID- 27200852 TI - Cost-Effectiveness Analysis of Strontium Ranelate Verse Alendronate for Management of Osteoporosis Among Post-Menopausal Women in Malaysia Using A Markov Modelling Approach. PMID- 27200851 TI - Cost-Effectiveness of Multiple Anti-Osteoporotic Therapies for Secondary Fracture Prevention in Japan. PMID- 27200853 TI - Cost-Utility Analysis of Certolizumab Pegol Plus Methotrexate for the Treatment of Moderate-To-Severe Active Rheumatoid Arthritis In Greece. PMID- 27200854 TI - Rituximab as First Choice for Patients With Refractory Rheumatoid Arthritis: Cost Effectiveness Analysis in Iran Based on A Systematic Review and Meta-Analysis. PMID- 27200855 TI - Mabthera(r) (Rituximab) for the Treatment of Severe Granulomatosis With Polyangiitis (Gpa) and Microscopic Polyangiitis (Mpa) - A Cost-Utility Model for the United Kingdom. PMID- 27200856 TI - Work Productivity Loss Due To Rheumatoid Arthtiris (Ra), Crohn's Disease (Cd) And Psoriasis (Ps) In Poland. PMID- 27200857 TI - Organizational and Management Impact Analysis of Using the New Subcutaneous Formulation of Tocilizumab in Selected Italian Rheumatology Centers. PMID- 27200858 TI - Systematic Review and Meta-Analysis of Persistence With Denosumab in Patients With Osteoporosis. PMID- 27200859 TI - Long-Term Work Productivity Costs Among Subjects With Early Rheumatoid Arthritis A Nationwide Analysis Based on 7,831 Subjects' Sickness Absence Days and Income. PMID- 27200860 TI - Characterizing Work Productivity Loss In Incident Rheumatoid Arthritis In Sweden. PMID- 27200861 TI - A Comparison of the Impact of Rheumatic Diseases and Other Chronic Diseases on Early Retirement in Portugal. PMID- 27200862 TI - Cost of Pharmacotherapy in Polish Patients With Rheumatoid Arthritis. PMID- 27200863 TI - Use of Medication Reminders in Patients With Rheumatoid Arthritis. PMID- 27200864 TI - Persistence Rate With Subcutaneous Biologic Therapies in Patients With Rheumatoid Arthritis (Ra). PMID- 27200865 TI - Treatment Persistence With Subcutaneous Biologic Therapies in Patients With Psoriatic Arthritis (Psa). PMID- 27200866 TI - Determinants of Non-Persistence to Antiosteoporotic Drugs by Using Administrative Database. PMID- 27200867 TI - Persistence Rate With Subcutaneous Biologic Therapies in Patients With Ankylosing Spondylitis (As). PMID- 27200868 TI - Impact of Medication Adherence by Using Indian Version Compliance Questionnaire Rheumatology (Cqr) and Medication Adherence Report Scale (Mars) Tools on Quality of Life of Patients With Rheumatoid Arthritis. PMID- 27200869 TI - Quality of Life in Psoriatic Arthritis: Consistent and Stable Across Datasets. PMID- 27200870 TI - Long-Term Maintenance of Improvements in Patient-Reported Outcomes With Certolizumab Pegol in Patients With Axial Spondyloarthritis, Including Ankylosing Spondylitis and Non-Radiographic Axial Spondyloarthritis: 96-Week Results of the Rapid-Axspa Study. PMID- 27200871 TI - Are Patients' Preferences Transferable Between Countries? A Cross-European Discrete-Choice Experiment to Elicit Patients' Preferences for Osteoporosis Drug Treatment. PMID- 27200872 TI - Patient Preferences in the Choice of Disease Modifying Anti-Rheumatic Drugs. PMID- 27200873 TI - Inadequate Pain Relief Among Patients With Primary Knee Osteoarthritis - Analysis From The Portuguese Sample Of The Survey Of Osteoarthritis Real World Therapies (Sort). PMID- 27200875 TI - Long-Term Maintenance of Improvements in Multiple Facets of Psoriatic Arthritis With Certolizumab Pegol: 96-Week Patient-Reported Outcome Results Of The Rapid Psa Study. PMID- 27200874 TI - Qualitative Equivalence Between A Paper and Electronic Tablet Version of the Womac(r)Nrs3.1 and Patient Global Assessment. PMID- 27200876 TI - Usability Testing of A Novel Pain Medication Diary Administered Electronically. PMID- 27200877 TI - Quality of Life in Patients With Axial Spondyloarthritis in Clinical Practice In Sweden: Baseline Results From A Longitudinal Study. PMID- 27200878 TI - Functional Status, Quality of Life And Work Disability for Patients With Rheumatic Diseases in Greece. PMID- 27200879 TI - Sustained Improvements in Workplace and Household Productivity and Social Participation With Certolizumab Pegol Over 96 Weeks in Patients With Psoriatic Arthritis. PMID- 27200880 TI - Quality of Life in Patients With Chronic Lumbosciatic Syndrome in the Slovak Republic. PMID- 27200881 TI - Reasons for Treatment Discontinuation of Biologics - Development and Validation of A Questionnaire. PMID- 27200882 TI - Assessing Willigness to Pay Among Psoriasis and Psoriatic Arthritis Patients. PMID- 27200883 TI - Sustained Improvements in Workplace and Household Productivity and Social Participation With Certolizumab Pegol Over 96 Weeks in Patients With Axial Spondyloarthritis, Including Ankylosing Spondylitis and Non-Radiographic Axial Spondyloarthritis. PMID- 27200884 TI - Predicting the Burden of Knee Arthroplasty Revision Over A 20-Year Horizon. PMID- 27200885 TI - Comparison of Clinical Characteristics of Patients With Rheumatoid Arthritis (Ra) Receiving Biologic Monotherapy and Biologic-Containing Combination Therapy in Europe. PMID- 27200886 TI - Anti-Tnf Biosimilars Indicated for Rheumatoid Arthritis are Increasingly Available in Europe: How Do Payers and Key Stakeholders Perceive Them? PMID- 27200887 TI - Market Access of Implantable Medical Devices - Part Ii: Decision Drivers Across Global Markets. PMID- 27200888 TI - Coping With A New Biologic Paradigm: Payer Strategies for the Purchasing of Complex Biosimilars. PMID- 27200889 TI - An Assessment of the Association Between Rural Status and Health Service Resource Use Among Patients With Ankle Sprains in Ontario. PMID- 27200890 TI - The Use of Clinical Data Repository for the Establishment of an Osteoporosis Registry in A Large Health Organization in Israel: Epidemiologic and Pharmaepidemiologic Findings. PMID- 27200891 TI - What Could the Future Hold? Simulating the Demand for Osteoarthritis (oa) Care in Alberta to Plan a Sustainable Oa Care System. PMID- 27200892 TI - Baseline Patient Characteristics of A Prospective Observational Study to Evaluate the Care Map of Women With Postmenopausal Osteoporosis (Pmo) in Switzerland (Campos). PMID- 27200893 TI - Increased Bone Mineral Density (Bmd) In Postmenopausal Women With Osteoporosis (Op) Receiving Two Denosumab Injections In Routine Clinical Practice In Bulgaria. PMID- 27200894 TI - Cachexia in the Us Health Care System. PMID- 27200895 TI - Gastrointestinal Risk Factors and Treatment Pattenrs of Rheumatoid Arthritis Versus Osteoarthritis Patients in Korea. PMID- 27200896 TI - Concomitant Use of Non-Steroidal Anti-Inflammatory Drugs (Nsaids) And Proton Pump Inhibitors (Ppis) in Newly Diagnosed Patients With Osteoarthritis (Oa), Rheumatoid Arthritis (Ra) or Ankylosing Spondylitis (As). PMID- 27200897 TI - The Burden of Parkinson Disease Amongst Caregivers in Spain Over 4 Years. PMID- 27200898 TI - A Systematic Review and Network Meta-Analysis of Pharmacological Therapies Used for Patients with Advanced Parkinson's Disease. PMID- 27200899 TI - Modelling the Impact of Persistence Improvements with an Electronic Injection Device on Escalation to 2nd Line Treatment in Patients with Relapsing Remitting Multiple Sclerosis (RRMS). PMID- 27200900 TI - Restless Leg Syndrome Detection in Hemodialysis. PMID- 27200902 TI - Image-Guided Navigation Systems (IGNS) Improve Accuracy of Catheter Placement in Shunted Hydrocephalus Patients. PMID- 27200901 TI - A Comprehensive Literature Review of the Burden of Gaucher Disease. PMID- 27200903 TI - Risk of Relapse Among Propensity Score Matched Multiple Sclerosis Patients Receiving Natalizumab or Platform Therapy in the US. PMID- 27200904 TI - Prevalence of Cystic Fibrosis Among the U. S. National Medicaid Population. PMID- 27200905 TI - Cerebrospinal Fluid f"-Amyloid1-42 Levels in the Differential Diagnosis of Alzheimer's Disease - Systematic Review and Meta-Analysis. PMID- 27200906 TI - A Real-World Assessment of Annual Multiple Sclerosis Prevalence and Disease Modifying Drug Treatment Rates Using an Administrative Claims Database. PMID- 27200907 TI - Evaluation of Disability Progression as an Endpoint in Clinical Trials for Relapsing-Remitting Multiple Sclerosis (RRMS): Comparison of the Define and Confirm Studies. PMID- 27200908 TI - The Clinical Evidence Base of Treatment Options in Alzheimer's Disease: A Systematic Literature Search. PMID- 27200909 TI - Assessing the Comparative Outcomes from Teriflunomide and Dimethyl Fumarate Studies in Relapsing Ms: Use of "Number Needed to Treat" Analysis. PMID- 27200910 TI - The Characteristics of Multiple Sclerosis in Iran. PMID- 27200911 TI - Epidemiology of Multiple Sclerosis in Latin America: Critical Analysis of the Literature. PMID- 27200912 TI - Entacapone did not Increase Prostate Cancer Risk or Mortality in Patients with Parkinson's Disease. PMID- 27200913 TI - The Clinical and Economic Value of Antibiotic-Impregnated Shunt Catheters (AISC) in the Treatment of Hydrocephalus. PMID- 27200914 TI - Budget Impact Analysis of Fingolimod in Relapsing Remitting Multiple Sclerosis. PMID- 27200915 TI - The Cost Burden of Switching Patients with Relapsing-Remitting Multiple Sclerosis from Glatiramer Acetate To Newly-Approved Disease Modifying Therapies. PMID- 27200916 TI - Improving Clinical Outcomes and Health Care Resources Utilization in Multiple Sclerosis: A Portuguese Hospital Perspective. PMID- 27200917 TI - Cost Analysis of two Aftercare Strategies in Chronic Continuous Intrathecal Baclofen Therapy in Patients with Intractable Spasticity. PMID- 27200918 TI - Alzheimer's Disease: Medication Costs and Impact of Generic Substitution. PMID- 27200919 TI - Systematic Review of the Economics of Multiple Sclerosis in Latin America. PMID- 27200920 TI - Cost Analysis of the Use of Glatiramer Acetate Compared to Interferon-A in Patients with Relapsing-Remitting Multiple Sclerosis and Spasticity in Spain. PMID- 27200921 TI - Costs Associated with the Use of Enzyme-Inducing Anti-Epileptic Drugs Versus Non Enzyme-Inducing Anti-Epileptic Drugs: A Systematic Review. PMID- 27200922 TI - Pharmacoeconomic Aspects of Multiple Sclerosis Treatments in Iran. PMID- 27200923 TI - Pharmacoeconomic Study of Botulinium Toxin Type a in Treatment of Post-Stroke Spasticity in the Russian Federation: Cost-Effectiveness Analysis. PMID- 27200924 TI - Does Current Portuguese Financing Model for Multiple Sclerosis Covers for Estimated Needs? PMID- 27200925 TI - Relationship Between the Direct Medical Costs and Direct Non-Medical Costs of Parkinson's Disease According to Disease Severity During 4 Years of Follow-Up in Spain. PMID- 27200927 TI - Cost Comparison of Deep Drain Stimulation (DBS) and Continued Subcutaneous Apomorphine Infusion (CSAI) in Patients with Advanced Parkinson's Disease. PMID- 27200926 TI - Retrospective Analysis of the Economic Burden of U. S. Long-Term Care Facility Residents Diagnosed with Parkinson's Disease. PMID- 27200928 TI - Health Care Resource Use and Cost Of Multiple Sclerosis in Slovakia: Results from the National Cross-Sectional Study. PMID- 27200929 TI - Nuedexta for the Treatment of Pseudobulbar Affect: Estimating the Financial Impact to the Scottish NHS. PMID- 27200930 TI - Clinical Outcomes and Health Care Resource Utilization in a 1-Year Observational Study of Patients with Non-focal Disabling Spasticity who are Resistant or Intolerant to Oral Therapy Treated with Intrathecal Baclofen Therapy at the Institut Guttmann (Spain). Epice Study. PMID- 27200931 TI - Financial and Clinical Implications of Intramuscular Versus Subcutaneous Interferon Beta-1a in Portugal, Based on the Findings from the Cochrane Collaboration Review of First-Line Treatments for Relapsing-Remitting Multiple Sclerosis. PMID- 27200932 TI - Whole Exome Sequencing as a Diagnostic Tool for Complex Neurological Disorders. PMID- 27200933 TI - Analysis of Expenditure in Multiple Sclerosis Disease Modifying Therapies Evolution Between 2004-2013 in Spain. PMID- 27200934 TI - Cost of Health Care Services Offered by Parkinson Disease Associations in Spain. PMID- 27200935 TI - The Impact of Adherence and Development of Neutralizing Antibodies to Interferons beta on Treatment of Multiple Sclerosis in the Czech Republic. PMID- 27200936 TI - Cost-Effectiveness Evaluation of Data from the Evidence (Evidence of Interferon Dose-Response: European North American Comparative Efficacy) Study. PMID- 27200937 TI - An Economic Evaluation of Subcutaneous and Intramuscular Interferon Beta-1a in Multiple Sclerosis Using a Direct Head-To-Head Study. PMID- 27200938 TI - Economic Evaluation of Lacosamide in the Management of Epileptic Partial Onset Seizures in Greece. PMID- 27200939 TI - Comparison of a Markov Cohort Model and a Discrete-Event Simulation for Economic Analyses of Treatments for Multiple Sclerosis. PMID- 27200940 TI - Cost-Effectiveness of Subcutaneous Verse Intramuscular Interferon Beta-1A In Portugal Based on the Findings of Cochrane Collaboration Review of First-Line Treatments for Relapsing-Remitting Multiple Sclerosis. PMID- 27200942 TI - Cost-Effectiveness of Subcutaneous Interferon Beta-1A in a Sub-Population of Multiple Sclerosis Patients (Kurtzke Expanded Disability Status Scale [EDSS]: >3.5-5.0). PMID- 27200941 TI - Treating Verse Non-Treating Obsturictive Sleep Apnea in Italy and France: A Markov Model-Based Cost-Effectiveness Analysis. PMID- 27200944 TI - The Long-Term Value of Glatiramer Acetate for the Treatment of Relapsing Remitting Multiple Sclerosis in the Netherlands. PMID- 27200943 TI - A Cost-Utility Analysis of Sacral Anterior Root Stimulation (SARS) Compared to Medical Treatment in Complete Spinal Cord Injured Patients with a Neurological Bladder. PMID- 27200945 TI - Cost-Utility Analysis (cua) Of First-Line Disease-Modifying Treatments (DMT) Versus Best Supportive Care (Bsc) In Finnish Relapsing-Remitting Multiple Sclerosis (RRMS) Patients. PMID- 27200947 TI - Cost-Minimisation Analysis of Colistimethate Sodium in Serbia- off Label Use Approach. PMID- 27200946 TI - Health Care Utilization and Costs of Medicaid Program Services for Patients Diagnosed with Multiple Sclerosis. PMID- 27200948 TI - Cost-Effectiveness Model Results of Intrathecal Baclofen Therapy Compared to Conventional Medical Management in Patients with Non-Focal Disabling Spasticity Who are Resistant or Intolerant to Oral Therapy at the Institut Guttmann. PMID- 27200949 TI - Expected Value of Partial Perfect Information for the Disability Progression Efficacy of Teriflunomide and Fingolimod in the Treatment of Relapsing-Remitting Multiple Sclerosis. PMID- 27200950 TI - Long-Term Costs and Consequences of Patients with Familial Chylomicronemia Syndrome - A Simulation Model Approach. PMID- 27200951 TI - Using a Panel Survey to Identify Predictors of Disease-Modifying Drug Adherence in Patients with Multiple Sclerosis. PMID- 27200952 TI - Persistence with Fingolimod Versus Dimethyl Fumarate in Patients with Multiple Sclerosis: Retrospective Analysis of us Open-Source Pharmacy Data. PMID- 27200953 TI - Working Ability and Monetarily Valued Productivity of Patients with Multiple Sclerosis Treated with Natalizumab. PMID- 27200954 TI - Modelling the Persistence of Disease-Modifying Drug Treatment (DMT) and its Independent Drivers in Finnish Multiple Sclerosis (MS) Patients: Parametric Survival Modelling. PMID- 27200955 TI - Quality of Life Among Patients with Multiple Sclerosis Treated with Prolonged Release Fampridine 10 Mg Tablets for Walking Impairment. PMID- 27200956 TI - The Effect of Insomnia and Insomnia Treatment Side Effects on Health Status, Work Productivity, and Health Care Resource Use. PMID- 27200957 TI - Humanistic Research Outcomes in Multiple Sclerosis: Review of the Literature from Latin America. PMID- 27200958 TI - Health-Related Quality of Life in Migraine Without Aura Based on Attack Frequency: A time Trade-Off Study. PMID- 27200959 TI - Persistence in Open and Closed Data Sources: A Study of Fingolimod Verse Interferons/Glatiramer Acetate in Patients with Multiple Sclerosis. PMID- 27200960 TI - Comparison of the Valuation of Treatment Alternatives in Parkinson's Disease with Best-Worst Scaling, Time Trade-off and Visual Analogue Scales. PMID- 27200961 TI - The Humanistic and Economic Burden of Partial Onset Seizures in the Europe Five and Brazil Using a Patient Survey. PMID- 27200962 TI - The Value of Diagnostic Tests for Alzheimer's Disease: Discrete-Choice Experiment and Contingent-Valuation. PMID- 27200963 TI - Factors Associated with Caregiver's Burden in Relapsing-Remitting Multiple Sclerosis and Satisfaction with Current Therapies. MS-Feeling Study. PMID- 27200964 TI - The Burden of Primary Generalized Tonic-Clonic Seizures in Europe and the United States: An Analysis of The National Health and Wellness Survey. PMID- 27200965 TI - Impact of Caregiving for Patients with Alzheimer's Disease and Dementia on Psychiatric and Clinical Comorbidities in Brazil. PMID- 27200966 TI - Antiepileptic Drug (AED) Treatment Sequencing in the Uk in Patients with Epilepsy: Real-Life Practice Data Using CPRD. PMID- 27200967 TI - Significant and Meaningful Improvement in Treatment Satisfaction with Teriflunomide Versus Subcutaneous IFNB-1A in Patients with Relapsing MS Results from Tenere. PMID- 27200968 TI - Evaluating Working Ability and Quality of Life of Patients with Multiple Sclerosis. PMID- 27200969 TI - Cognitive Impairment and Health Related Quality of Life in Relapsing Remitting Multiple Sclerosis. PMID- 27200970 TI - Psychometric Analyses to Inform Item Reduction and Evaluate Sensitivity of the Early Mobility Impairment Questionnaire for Multiple Sclerosis. PMID- 27200971 TI - Analysis of the Recent HTA Decision Making Landscape for Multiple Sclerosis Therapies - Trends and Future Opportunities. PMID- 27200972 TI - Comparing Characteristics of Hungarian "Real Life" Patients With Participants of RCTS: First-Line Disease Modifying Therapies in Multiple Sclerosis. PMID- 27200973 TI - Characteristics of Patients with Relapsing Remitting Multiple Sclerosis Taking Injectable and Oral Disease Modifying Treatments in the United States. PMID- 27200974 TI - Frequency of Outpatient Physiotherapy Services in Neurology Diseases in Hungary. PMID- 27200975 TI - Patterns of Use of Tests to Monitor Disease Activity Among Patients With Relapsing Remitting Multiple Sclerosis in the United States and Europe. PMID- 27200976 TI - Adoption of Oral Disease Modifying Treatments to Manage Patients with Relapsing Remitting Multiple Sclerosis from 2011-2013 in the United States. PMID- 27200977 TI - Attitudes of Patients Toward Generic Substitution and Implication for Practice in Slovakia: First Results From Adopting The Law in 2012. PMID- 27200978 TI - The Simultaneous Effects of Pharmaceutical Policies from Payers' and Patients' Perspectives. Italy as a Case Study. PMID- 27200979 TI - Patient, Insuree and Public Participation in Health Technology Assessment: An International Comparison. PMID- 27200980 TI - The Effect of Degressive Financing Method on the Hungarian Drg Based Hospital Reimbursement Between 2011-2013. PMID- 27200981 TI - Awareness and Interest in the United States Health Insurance Marketplace. PMID- 27200982 TI - Nub Status - A 2014 Situation Analysis for Drugs: Oncology As Leading Therapeutic Area. PMID- 27200983 TI - Price Comparison in the European Pharmaceutical Market. PMID- 27200984 TI - Health-Economics in Czech Republic: Can Formal Health-Economic Methodology Improve The Quality Of Submitted Analysis? PMID- 27200985 TI - A Gender Medicine Post-Hoc Analysis: Background and Methods of the Metagem Project. PMID- 27200986 TI - Trends in Physical and Occupational Therapy Utilziation in the Us And Western Europe. PMID- 27200987 TI - Multicriteria Decision Analysis and Cost Analysis in Health Care Decision Making: A Literature Review. PMID- 27200988 TI - Letting The Data Speak: A Shift of the Pharmaceutical Spending to Households in Greece. PMID- 27200989 TI - Are Prices of Patent-Protected Pharamceuticals in the Top 5 Eu Countries Converging? PMID- 27200990 TI - Impact Of Pharmacoeconomic Guidelines on the Reimbursement Process of Medicines In Serbia In 2014. PMID- 27200992 TI - How is Current Pharmaceuticals Pricing Policy on Generics Performing in Turkey Regarding Price Erosion? PMID- 27200991 TI - Cost-Effectiveness of Targeted Pharmacotherapy - A Systematic Review of the Literature. PMID- 27200993 TI - Economic Burden of Intravenous Iron Products In Public Hospitals of Paris and Impact of Their New Hospital-Restricted Status. PMID- 27200994 TI - Boosting Biosimilars Uptake in European Countries. PMID- 27200995 TI - Impact of Health Policy Changes on Trends of Pharmaceutical Market in Turkey. PMID- 27200996 TI - Trends In Clinical Drug Development Timeframes, 1981-2013 - An Example From Virology. PMID- 27200997 TI - The Effects of Reforms, Price Cuts and Global Budget Implementation on Biotechnological Medicine Sales Which Have Annual Average Highest Amount Of Sales Between 2008-2013 In Turkey. PMID- 27200998 TI - The Impact of Cost Containment Reforms to the Pharmaceutical Benefits Scheme (Pbs) On Prescribing Volumes And Expenditure In Australia: 1992 To 2011. PMID- 27200999 TI - A Multi-Stakeholder (Physician, Payer, Patient, and Industry) Qualitative Analysis of the Policies That Would Support A Sustainable European Biosimilars Medicines Market Combined With A Quantitative Analysis of the Multi-Stakeholder Benefits A Sustainable Medicines Market Would Deliver. PMID- 27201000 TI - Is the French Liste-En-Sus Still Supporting Access To Innovative Medicines? PMID- 27201001 TI - Quantification of Switching Trends in the Greek Pharmaceutical Market During the Period Of Crisis. PMID- 27201002 TI - Implications Of External Price Referencing of Pharmaceuticals in Middle East Countries. PMID- 27201004 TI - Impact of Health Policy Changes on the Growth Locally Manufactured and Imported Pharmaceutical Markets of Top Selling Atc1 Phramaceutical Group (Alimentary and Metabolism (A0) In Turkey. PMID- 27201005 TI - An Overview of the Biosimilar Market in the Us. PMID- 27201003 TI - Effects of Reference Price System on Medicines Which Have Annual Average Highest Amount Of Sales Of Between Years 2008-2013. PMID- 27201006 TI - Impact of Health Policy Changes on the Growth Locally Manufactured and Imported Pharmaceutical Markets In Turkey. PMID- 27201007 TI - The Effects of Reforms, Price Cuts And Global Budget Implementation on Original/Generic Medicine Sales Which Have Annual Average Highest Amount Of Sales Between 2008-2013 In Turkey. PMID- 27201008 TI - Saving Money in Health Care: Cost Effectiveness of Individual Drugs (As By Nice) Or Budget Cuts (As Under Pprs)? PMID- 27201009 TI - Impact of Health Policy Changes on the Cost Sales of 5 Top Selling ATC1 Phramaceutical Groups in Turkey. PMID- 27201010 TI - Transformation of Green Card Program for the Poor: One Step Further to Universal Health Care Coverage in Turkey. PMID- 27201012 TI - Impact Of Health Policy Changes on Unit Sales of 5 Top Selling Atc1 Phramaceutical Groups In Turkey. PMID- 27201011 TI - Characteristics of The Medicines Which Have Annual Average Highest Amount Of Sales Of Between Years 2008-2013. PMID- 27201014 TI - The Grass is Always Greener on the Other Side or Why There Is Little Meaning in International Pharmaceutical Price Comparison. PMID- 27201013 TI - Applicability of Turkish Pricing Policy on Price Increases. PMID- 27201015 TI - Generic Penetration Within Top-10 Genericized Molecules - Greece Versus Major European Countries. PMID- 27201016 TI - An Analysis of the 2014 Moroccan Drug Price Cuts. PMID- 27201017 TI - Prevention and Management of Medicine Shortages in Belgium, France and from The Perspective of the European Union. PMID- 27201018 TI - Evaluating Rates of Potential Generic Substitution for Prescription Drugs: Can We Improve On Existing Incentive Schemes? PMID- 27201019 TI - Promoting Quality Use of Generic Medicines: Knowledge, Attitudes And Practices of Community Pharmacists in A Middle Eastern Country. PMID- 27201020 TI - Expedited Regulatory Review and Authorisation of Medicines and Their Subsequent Appraisal By Hta Agencies in the European Union. PMID- 27201022 TI - Trends in Time To Market Access In Europe - Is It Getting Better? PMID- 27201023 TI - Market Access for Medical Devices: Adapting to Change. PMID- 27201024 TI - Qualitative Research on the Impact Of European Hospital Procurement Practices on Market Access For Disposable Medical Devices. PMID- 27201021 TI - Challenges: in Implementing HTA In The Reimbursement Decisions In Algeria / A Compartive Analysis. PMID- 27201025 TI - Pricing of Medicines In Poland - Two-Year Overview Of How The New Law Affected Costs Of Reimbursement. PMID- 27201026 TI - The Impact of the Information System of Medical Devices in Portugal. PMID- 27201027 TI - Accessing the Medical Device Market in the People's Republic of China--Policy Changes Since the Restructuring of the China Fda. PMID- 27201028 TI - Therapeutic Positioning Report: New Collaborative Network of Drug Assessment in Spain - The Start Of P&R Based On Relative Effectiveness? PMID- 27201029 TI - Are There Any Commonalities In Payer Requirements and Reimbursement Pathways for Medical Devices in the Dach (Germany, Austria, Switzerland) Region? PMID- 27201031 TI - Analysis of Cost-Effectiveness Assessments In France By The French National Authority For Health (Has). PMID- 27201030 TI - Integration of Cost-Effectiveness Assessment in the Market Access Scheme of Drugs and Medical Devices In France. PMID- 27201032 TI - The Relevance of Health Services Research for the Pharmaceutical Industry in Germany -Results of A Representative Online Survey. PMID- 27201033 TI - When Gender Matters: Impact of Fda Safety Warning on Dispensed Zolpidem Dose. PMID- 27201034 TI - Impact of Cost- Containment Policies on Biosimilars Market. PMID- 27201035 TI - Economic Impact of Drugs De-Funding and Pharmaceutical Co-Payment. PMID- 27201036 TI - Availability of Risk Sharing Agreements in the Turkish Pharmaceutical Sector. PMID- 27201037 TI - The Benefits and Challenges of Submitting to the Nice Medical Technologies Evaluation Programme-Manufacturer Perceptions And Experiences. PMID- 27201038 TI - Non-Steroidal Anti-Inflammatory Drugs in Household Drug Supplies in Serbia. PMID- 27201039 TI - Pharmacoeconomic Analysis of Antifungal Drug Use in the Intensive Care Unit. PMID- 27201040 TI - Prescribing Pattern of Antibiotics In Neonates in a Tertiary Care Hospital. PMID- 27201041 TI - Using Data Envelopment Analysis (Dea) To Rank Gp's According To Their P4p Quality and Efficiency Scores. PMID- 27201042 TI - Do Quality or Efficiency Indicators Inside French P4p Perimeter Influence Quality Or Efficiency Indicators Outside P4p? PMID- 27201043 TI - Impact of the Early Benefit Assessment on A Pharmaceutical's Real Consumption in Germany. PMID- 27201045 TI - Trend Comparison of the Colombian Multidimensional Poverty Index, Inequities in Maternal Mortality, Neonatal Mortality and Gini Coefficient, 1997-2011. PMID- 27201044 TI - Advantages of Extemporaneous Dosage Forms in Ukraine. PMID- 27201046 TI - Nurses Verse Other Health Professionals Perceptions on Quality and Safety Culture Elements in Greek Hospitals. PMID- 27201047 TI - Pharmaceutical Market Access in Emerging Markets Through Innovative Patient Access Schemes. PMID- 27201048 TI - Patient Envolvement in Reimbursment of Drugs in Slovakia. PMID- 27201049 TI - Towards Universal Health Care- A Review of the Basic Basket of Care Associated With Universal Health Care Delivery Models. PMID- 27201050 TI - Do Nice Decisions Affect Decisions in Other Countries? PMID- 27201051 TI - Experiences With Price Competition of Biosimilar Drugs in Hungary. PMID- 27201052 TI - Measuring the Efficiency of Hungarian Hospitals by Data Envelopment Analysis. PMID- 27201053 TI - National Rare Disease Strategies: The Current State for Orphan Drug Market Access in European Union (Eu) Member States. PMID- 27201054 TI - Impact of Prior Authorization Restrictions on Resource Utilization and Costs In US Health Plans: A Review Of Literature. PMID- 27201055 TI - Complications, costs And Resource Utilization in Real-World Complex Abdominal Wall Reconstruction Patients. PMID- 27201056 TI - The Growing Financial and Quality-of-Life Burden Associated With Atrial Fibrillation (Af), Diabetes, Chronic Obstructive Pulmonary Disease (Copd) And Asthma in Ireland. PMID- 27201057 TI - A Quantification of Expenditure on Hospital Stays In 5 European Countries. PMID- 27201058 TI - What Is Working Well In Louisiana For Us Employers: A Descriptive Analysis of Employers Actively Engaged In Promoting Employee Health. PMID- 27201059 TI - Do Specialty Drugs Offer Greater Value for Money Than Traditional Drugs? PMID- 27201060 TI - R&D Investments, Intangible Capital and Profitability in the Pharmaceutical Industry. PMID- 27201061 TI - HTA Informed Price Negotiations: Cost Savings To The Health Payer in Ireland. PMID- 27201062 TI - Setting Targets For Public Spending Under Eu-Imf Assistance To Portugal - The Case Of Health Care and Pharmaceuticals. PMID- 27201063 TI - Access To Non Communicable Disease Medicines in India: A Comparative Analysis of State Level Public Procurement Data. PMID- 27201064 TI - Constructing A Comorbidity Index According To Iso-Resource Consumption. PMID- 27201065 TI - Assessing Assessment: Does Health Technology Assessment Do Its Job of Controlling Costs Without Compromising Quality? PMID- 27201066 TI - The Trend of the Prices Of New Marketed Drugs in Turkey. PMID- 27201067 TI - Correlation Between Hospitalized Morbidity and Cost of Treatment of Selected Chronic Diseases. PMID- 27201068 TI - Patient Reported Outcomes and Their Relevance in Reimbursement Decisions. PMID- 27201069 TI - Interventions and Policy Measures in Health Care And Pharmaceutical Sector To Increase Effeciency And Recovery of Greek Health Care System. PMID- 27201070 TI - Determinants of Hospitals' Attractiveness For Patients: Application to Expensive Drugs. PMID- 27201071 TI - Economic Impact of Clinical Researches to the Research Centers and Reimbursement Systems in Turkey. PMID- 27201072 TI - Pharmaceutical Developpement: Africa an Emergent Market. PMID- 27201073 TI - Funding Integrated Health Care Services. PMID- 27201074 TI - Market Analysis in Regard to Biologically Active Supplements And Medicines in Armenia. PMID- 27201075 TI - Impact of 2011 German Health Care Reform on Prices. PMID- 27201076 TI - Real World Data (Rwd) At T=4 in the Netherlands. PMID- 27201077 TI - Opportunity Costs of Implementing Nice Decisions in NHS Wales. PMID- 27201078 TI - Acceptance Of Telemonitoring By Health Care Professionals in Germany: A Question Of Financial Conditions. PMID- 27201079 TI - Gender-Related Behaviors in Drug Consumption In Italy. PMID- 27201080 TI - A Comparison of Cobb-Douglas, Translog and Additive Models of the Production Functions of Inpatient Services In Public Hospitals. PMID- 27201081 TI - External Reference Pricing Impact of the Integration of the Amnog Discount In The List Price. PMID- 27201082 TI - Home Pharmacies: An Insight In Self-Medication Practice. PMID- 27201083 TI - Value of Life And Cost of Pre-Mature Deaths With The Perspective Of Productivity As Net Tax Revenue: A Comparison In Usa, Canada, Japan and Australia. PMID- 27201084 TI - Patterns and Predictors of Hospital Readmission in Taiwan. PMID- 27201085 TI - Value of Life And Cost of Pre-Mature Deaths With the Perspective of Productivity As Net Tax Revenue for Turkey. PMID- 27201086 TI - Switching Patients With Primary Antibody Deficiencies to Home-Based Subcutaneous Immunoglobulin: Economic Evaluation of An Interprofessional Drug Therapy Management Program. PMID- 27201088 TI - Secure System for Iv Administrations: Health Economic Impact Of A "Smart" Infusion Safety System. PMID- 27201087 TI - Value of Life and Cost of Pre-Mature Deaths With The Perspective of Productivity As Net Tax Revenue: A Comparison in France, Germany, Italy, Spain, United Kingdom. PMID- 27201090 TI - Community Pharmacist Perceptions of Generic Medicines: A Survey in Tehran. PMID- 27201089 TI - Gender Medicine in Germany: What is so Difficult about its Implementation? - An Empirical Study in Germany. PMID- 27201091 TI - Building A "High-Alert/High Risk Medications Reminder System" To Improve Patient Safety. PMID- 27201092 TI - Assessment of Validity of An Indicator Module In Identification of adverse Drug Events in Patients of Medicine Department. PMID- 27201093 TI - Value of Life And Cost of Pre-Mature Deaths With The Perspective Of Productivity As Net Tax Revenue: A Comparison In Argentina, Brazil And Mexico. PMID- 27201094 TI - Cost-Effectiveness of Telemedicine: Lessons To Learn From An International Review. PMID- 27201095 TI - Exposure To Potential Drug-Drug Interactions in Teaching Hospital Of South Punjab, Pakistan. PMID- 27201096 TI - Can A Global Value Dossier Meet Headquarters and Affiliates's Expectations? PMID- 27201097 TI - Management of Crises and Risks in German Hospitals - Factors Influencing Medication Errors. PMID- 27201098 TI - Comparison of Expected Versus Actual Cost Consequence Of Reimbursed Drugs in the Netherlands Between 2009 and 2013. PMID- 27201099 TI - Predicted Versus Actual Budget Impact of High-Cost Drugs In Ireland. PMID- 27201100 TI - Costs and Effectiveness of the Mediguide Technology in the Conditions of the Czech Republic. PMID- 27201101 TI - Barriers of Pharmaceutical Care in Community Pharmacies: Evidences From Emerging Counteries. PMID- 27201102 TI - Comparison of Post-Authorisation Measures From Regulatory Authorities With Additional Evidence Requirements From HTA Bodies in Germany. PMID- 27201103 TI - Regulatory Approval To Patient Access, An Evaluation of Eu5 And Us National Timing Differences: An Update. PMID- 27201104 TI - Standard Costs for Health Economic Evaluations: An International Comparison. PMID- 27201105 TI - Black Box Amnog Rebates: What Is Driving the Price in the Negotiation With The Gkv-Spitzenverband? PMID- 27201106 TI - Redel Study: Differences in Reimbursement Delays in Cee Countries. PMID- 27201107 TI - Impact of Chronic Diseases on Health Care Expenditures: A Multivariate Linear Model From Pharmaceutical Reimbursement Data. PMID- 27201108 TI - The Effect of China's Basic Medical Insurance Schemes on Health Service Utilization. PMID- 27201109 TI - Price Negotiation For Pharmaceuticals in Germany: High Influence Of Eu Price Weighting Method. PMID- 27201110 TI - A Payers Perspective to Pharmaceutical Market Access: Defining Market Access. PMID- 27201111 TI - Market Access Pathway for Medical Nutrition in Europe and The Us. PMID- 27201112 TI - The Reimbursement of Expensive Drugs In Hospitals in Western European Countries. PMID- 27201113 TI - Pay-For-Performance: Balancing Cost and Care. PMID- 27201114 TI - Swisshta Recommendation as an Optimal approach for Pragmatic HTA Evaluations? An International Comparison. PMID- 27201115 TI - Review of Pricing And Reimbursement Systems in South-Eastern Europe. PMID- 27201116 TI - Pricing and Reimbursement Environment For A Biologic Obtaining A Licence In A Second Indication in Key European Countries. PMID- 27201117 TI - Cost and Quantity Characteristics of Medical Devices In Slovakia. PMID- 27201118 TI - The Greek Health Care Reform After Troika's Involvement: The Potential Impact on Global Pricing and Access Strategy. PMID- 27201119 TI - A Comparison of Factors Influencing Reimbursement and Coverage Decisions in Scotland (Smc), The Netherlands (Nzi) and Germany (G-Ba). PMID- 27201121 TI - Hta Status of Biosimlars Across the UK and Ireland. PMID- 27201120 TI - A Comparison of Additional Benefit Scores in Germany (Gba) and France (Has). PMID- 27201122 TI - Does Not Reaching an Agreement on the Final Nice Scope Have Any Impact on The Final Apraisal Outcome? PMID- 27201124 TI - Time Limits Restriction in Germany. PMID- 27201123 TI - Product Quality Aspect in Reimbursement of Medical Devices: Comparison of Turkey Verse Europe. PMID- 27201126 TI - Reimbursement Trends and Evidence Requirements for Ultra-Orphan Therapies Across Europe: Optimising Market Access in Increasingly Challenging Markets. PMID- 27201125 TI - An Examination of the Regulatory and Reimbursement Processes for Biobetters and Comparison With Biosimilars. PMID- 27201127 TI - Global HTA Assessments of Ultra-Orphan Products: A Case Study Of Eculizumab (Soliris) and Iduronate-2-Sulfatase (Elaprase). PMID- 27201128 TI - Evidence-Based Market Access Value Resource: Navigating The Hurdles for A Biologic Obtaining A License In A Second Indication in Key European Countries. PMID- 27201129 TI - National Health Insurance Fund Drug Expenditure in Bulgaria, 2007-2012: Reference Based Pricing Alone or in Combination With Other Approaches to Pricing. PMID- 27201130 TI - Evaluation of Social Welfare Part of Hungarian Drug Provision System. PMID- 27201131 TI - Analysis of New Model of Therapeutic Positioning Reports As A P&R Decision-Making Tool in Spain. PMID- 27201132 TI - Determination of Referral Utilization Rate: Linking Households To Health Care System; Kenyan Rural Setting Experience. PMID- 27201133 TI - Medicare Provider Utilization and Payment Data: The Book to Bill Gap. PMID- 27201134 TI - Claims Reimbursement Analysis of the National Health Insurance Scheme in Ghana. PMID- 27201135 TI - Provincial Entry of New Drugs In China. PMID- 27201136 TI - Using The Ispor 2013 European Congress as a Big Data Case Study. PMID- 27201137 TI - Common Illnesses Identified by Community Health Workers in the Households and Referrred to Primary Health Facilities For Care. PMID- 27201138 TI - An Evaluation of Patient Satisfaction In Pafos, Cyprus With The "Europep" Instrument. PMID- 27201139 TI - Clinical Trial Activity in Greece From 2010 To 2012: Still Missing the Opportunities? PMID- 27201140 TI - Predictors of Working Motivation in Job Satisfaction Among Nurses in Cyprus. PMID- 27201141 TI - Factors Influencing Job Satisfaction Among Nurses of Pafos General Hospital in Cyprus. PMID- 27201142 TI - Legal and Ethical Implications of Using Data From Social Media Websites. PMID- 27201143 TI - Phenomenon of Inappropriate Drug Manufacturing in China - Past and Present. PMID- 27201144 TI - The Ecology of Medical Care in Japan Revisited. PMID- 27201145 TI - What Is The Proportion of Patients Who Return Counter Referral Slips to the Original Referral Service For Confirmation of Arrival to the Hospital? PMID- 27201146 TI - What Is The Patients' Median Delay From The Referring Community Health Worker To Arrival in the Link Health Facility? PMID- 27201147 TI - Choosing Important Health Outcomes For Comparative Effectiveness Research: A Systematic Review. PMID- 27201148 TI - The Role of Patients in Clinical Research and Evidence Based Decision Making as Reported Via A Survey of Patient Advocates. PMID- 27201149 TI - Drug Repurposing as An Efficient Strategy In Drug Development - Example Of Cns Area. PMID- 27201150 TI - Health Care Reform in China And The United States: A Tale of Two Nations Seeking To Improve Access To Affordable Coverage. PMID- 27201152 TI - Pharmacoeconomic Education in Brazilian Schools of Pharmacy. PMID- 27201151 TI - Components of Sustainable Health Systems: What Is Known About The Cost Effectiveness of Clinical Care? PMID- 27201153 TI - Application of A 'Nice Post-Hoc B/S Analysis' To the Nice Appraisal Process. PMID- 27201154 TI - Impact of Story Books on Promoting Knowledge and Behavior of 4th Stage Elementary Students About Rational Use of Medicines in Kermanshah Provine of Iran 2008. PMID- 27201155 TI - Clinical Trials in France: An Underexploited Opportunity. PMID- 27201156 TI - Will Value Based Assessment (VBA) Revolutionise The Nice Assessment? PMID- 27201157 TI - The Future of Education In HTA and Health Economics. PMID- 27201158 TI - Selection of Topics For Nice Technology Appraisal 2005-2011: What Matters Most? PMID- 27201159 TI - The Evolution of International Reference Pricing: An Analysis of 39 Countries. PMID- 27201160 TI - Making Sense of Nice's 'New' MTA and STA Process Guide: A Narrative Synthesis. PMID- 27201161 TI - Methodological Requirements Regarding Quality of Life Measurement in the Early Assessment of Benefit In Germany. PMID- 27201162 TI - Exploring The Flaws in Cost-Effectiveness Models That Lead to Rejection of Nice Submissions. PMID- 27201163 TI - Is it Possible to Predict The Market Access of a New Pharmaceutical in Germany? A Systematic Evaluation of Federal Joint Committee Decisions on Early Benefit Assessments According to The German Law For Reforming The Market of Pharmaceuticals. PMID- 27201164 TI - Nice Restrictiveness Compared To the Market Authorization. PMID- 27201165 TI - Trends and Key Decision Drivers For Rejecting An Orphan Drug Submission Across Five Different HTA Agencies. PMID- 27201166 TI - A Literature Review of Patient Advocacy Group (Pag) Involvement in HTA. PMID- 27201167 TI - Systematic Review of Economic Evaluation of Health Technologies Developed In Brazil From 1980-2013. PMID- 27201168 TI - Determination of Cost-Effectiveness Threshold For Malaysia. PMID- 27201169 TI - Predictors of German Amnog Decisions and GKV Rebate Negotiations: A Database Analysis. PMID- 27201170 TI - Hta Epidemiology Data in Different Geographical Regions: Investigation of Requirements For Oncology Drugs. PMID- 27201171 TI - The Risky Business of Drug Development: The Final Say of National Hta Agencies on A Pharmaceutical's Benefit During The Last Stretch of An Expensive, Long-Lasting And Arduous Development Journey - As Illustrated By The Decisions Of Germany's Gemeinsamer Bundesausschuss (G-Ba). PMID- 27201172 TI - Decision Drivers For Brazil: An Analysis of Conitec Recommendations. PMID- 27201173 TI - Out With The Old - In With The New: Would New Social Preference Weights For Eq-5d Inevitably Require A Reappraisal of Previous Cost-Effectiveness Determinations? PMID- 27201175 TI - Reality in Market Access In Germany and France - Comparative Analysis of Added Benefit Decisions on Innovative Pharmaceutical Therapies. PMID- 27201174 TI - Multicriteria Decision Analysis (MCDA) In HTA - Pilot Study in the Czech Republic. PMID- 27201176 TI - Rapid Relative Effectiveness Assessment of Pharmaceuticals: Transferability and Completeness of Information Derived From Global Value Dossiers To Complete A Eunethta Submission. PMID- 27201177 TI - Encepp-HTA Working Group Survey on Capacity To Conduct Research in Support Of Health Technology Assessment. PMID- 27201178 TI - What The English Could Learn From The Irish: Making The Nice Approval Process More Cost-Effective. PMID- 27201179 TI - Going Beyond The Qaly In Assessing The Benefits of Medical Devices. PMID- 27201180 TI - Inclusion and Consideration of Patient Preferences in Amnog Early Benefit Assessments. PMID- 27201181 TI - Exploring Uncertainty in Economic Evaluation Of Medicines: A Review of The First Manufacturers' Submissions To the French National Authority For Health (Has). PMID- 27201182 TI - Trends In Early Engagement Between Industry And HTA: Analysis of Scientific Advice Service Provided By Nice Since 2009. PMID- 27201184 TI - Measuring Extent of Access For Nice Health Technology Assessment Decisions: Trends From 2008 to 2013. PMID- 27201183 TI - A Comparison of International Health Technology Assessment Systems - Does The Perfect System Exist? PMID- 27201185 TI - Factors Influencing Dutch Drug Reimbursement Recommendations; A Database Analysis. PMID- 27201187 TI - Pricing Additional Benefit in Germany. PMID- 27201186 TI - Conditional Resolutions in the Amnog Early Benefit Assessment. PMID- 27201188 TI - Risk of Bias in Trial-Based Economic Evaluations. PMID- 27201189 TI - UK Value-Based Assessment: Will Scotland's Smc Approach It In The Same Way? PMID- 27201190 TI - Discrepancy Between National Drug Recommendations And Local Uptake in the Swedish Inpatient Sector. PMID- 27201191 TI - HTA Approach in Italy. Structure, Methods, And Process Of Veneto Region's Evaluation Of Pharmaceutical Effectiveness Unit (Unita Di Valutazione Dell'efficacia Del Farmaco, Uvef). PMID- 27201192 TI - The Inverse Correlation Between Internal And External Risk Under International Reference Pricing: An Analysis of Six European Countries. PMID- 27201193 TI - Understanding The Role of Subgroup Analysis And Tests For Homogeneity or Interaction in the Amnog Dossier. PMID- 27201194 TI - Quality Of Life - A Rarely Acknowledged Key Category Within The Amnog Process in Germany. PMID- 27201196 TI - Transferability of Economic Evaluations To Central and Eastern Euroepan and Former Soviet Countries. PMID- 27201195 TI - Combining Headroom and Return on Investment Analysis To Rank Potential Commercial Value of Six Medical Devices in Development. PMID- 27201197 TI - An Archetype For Classification and Comparison of Hta Activities in Latin America. PMID- 27201198 TI - Hta In The Brazilian Health Care System and Potential Lessons Learned For Other Brics States. PMID- 27201199 TI - Is G-Ba Strategically Discounting The Benefit Assessment of Relatively High Cost Drugs? PMID- 27201200 TI - An Update on Clinical And Economic Evidence Requirements for Advanced-Therapy Medicinal Products in Europe. PMID- 27201201 TI - The Definition and Role of Quality of Life In Germany's Early Assessment of Drug Benefit. PMID- 27201202 TI - Ten Years Of Development Studies In Health Technology Assessment In Brazil: Profile Of Studies And Operational Indicators. PMID- 27201203 TI - Romanian Quick-HTA Development In 2013. PMID- 27201204 TI - Correlation Between End-of-Life Status of A Treatment And Likelihood of A Patient Access Scheme in The Setting of A Nice Review in The UK. PMID- 27201205 TI - The Costs and Effects of Post-Authorisation Safety Studies For New Active Substances. PMID- 27201206 TI - Development of Hta in Turkey. PMID- 27201207 TI - First Experiences With The New Testing Examination and Treatment: Methods in Germany: Is This A New Amnog Clone? PMID- 27201208 TI - Disease Burden in Brazil and Health Technology Assessment: A Retrospective of Ten Years of Supporting. PMID- 27201209 TI - Determination of Major Chronic Diseases by Using Pharmaceutical Reimbursement Data From A Large Belgian Health Insurer Claims Database. PMID- 27201210 TI - Use Of Factor Analysis To Obtain Independent Health Performance Indicators. PMID- 27201211 TI - Impact of Economic Crisis on the Greek Health Care System and on the Population Health. PMID- 27201212 TI - Estimation of Stress Resistance of Medical Students in LVIV. PMID- 27201213 TI - Breastfeeding and Its Effect On The Probability of Occurance of the Probability of Occurance of the Disease And Related Costs. PMID- 27201214 TI - Supporting Interoperable Eu Patient Registries: Survey of Registry Holders' Needs. PMID- 27201215 TI - Type of Multimorbidity and Patient-Centered Care Among Elderly Medicare Beneficiaries. PMID- 27201216 TI - Guidance for Risk Sharing Agreements / Pay Per: Results SCHEMES FOR PHARMACEUTICALS IN CATALONIA (SPAIN). PMID- 27201217 TI - Guidance For Economic Evaluation and Budget Impact Analysis For Pharmaceuticals in Catalonia (Spain). PMID- 27201218 TI - Prescribing Patterns of General Practitioners (Gps) in Primary Health Care: Evidence From Greece. PMID- 27201219 TI - Evaluation of Medicine Prescription Pattern Using World Health Organization Prescribing Indicators in Iran: A Cross-Sectional Study. PMID- 27201220 TI - Impacts Of Bar-Code Medication Administration (Bcma) On Patients' Safety in Taiwan. PMID- 27201221 TI - The Effect of Procurement Design on Entry and Success of Generic Drug Firms. PMID- 27201222 TI - 10 Years Evaluation of Costs And Revenues Of Heath Care Services Provider Under The New Health Care Legislation and Price Policy. PMID- 27201223 TI - The Effect of Decentralised Public Health Care Provision on Accessibility To Medicines in Bosnia And Herzegovina. PMID- 27201224 TI - The Comparison of the Risk-Sharing Schemes Proposed in Reimbursement Applications Received By Ahtapol In 2012 and 2013. PMID- 27201225 TI - Pharmacoeconomic Evaluation For Reimbursement Purposes in Bulgaria: Recent Updates. PMID- 27201226 TI - Managed Entry Agreements in UK, Italy And Spain. PMID- 27201227 TI - The Possibility of Initiating True Risk-Sharing Agreements in the Current Economic Situation. PMID- 27201228 TI - Risk-Sharing Schemes In Poland - Analysis And Classification of Rss Proposed In Reimbursement Application Received by Ahtapol In 2013. PMID- 27201229 TI - Whatever Happened To Nice Value-Based Pricing? Welcome, Value-Based Assessment. PMID- 27201231 TI - Coverage With Evidence Development Activities Around The World: An Environment Scan. PMID- 27201230 TI - National Immunisation Technical Advisory Groups - A Framework For Assessment and Insights From Research. PMID- 27201232 TI - The Cost-Effectiveness Threshold For Orphan Designations in Poland Based on Reimbursement Decisions. PMID- 27201233 TI - Conflict Of Interest in HTA Recommendations and Case Law In France. PMID- 27201234 TI - Measuring and Observing Positive And Negative Externalities Caused By Vaccines: Do We Have The Right Assessment Approach Available? PMID- 27201235 TI - Market Access and Reimbursement: The Increasing Role of Real-World Evidence. PMID- 27201237 TI - Discontinuities Between Health Technology Assessment (HTA) and Health Care Service Objectives of the NHS. PMID- 27201236 TI - The Economic Value of Vaccination: Why Prevention Is Wealth. PMID- 27201238 TI - An Ethic System Overview: Brazilian Perspectives For Observational Studies. PMID- 27201240 TI - Early Nice Decision Problem Meetings: Implications For Cross-Functional Industry Teams. PMID- 27201239 TI - The Irish Cost-Effectiveness Threshold: Does It Support Rational Rationing or Might It Lead To Systematic Damage Of Ireland's Health System? PMID- 27201242 TI - Reimbursement Hurdles For High-Cost Brand-On-Brand Combinations and Impact on Patient Access. PMID- 27201241 TI - The Case For Early Payer Engagement. PMID- 27201243 TI - Market Access and Reimbursement Options For Orphan Durg Hospital Only Medicines In Europe - One Size Fits All? PMID- 27201244 TI - Economic Evaluation In Portugal - Establishment of The National Health Technology Assessment System (Sinats). PMID- 27201245 TI - Sustainable Health Care Systems: The Role of Therapeutic Value and Value Based Pricing. PMID- 27201247 TI - Proposed Framework for Patient And Public Involvement in the Hta Process In Ireland. PMID- 27201246 TI - Patient Access To Life-Saving Medication; Preventing Stock-Outs Due To Parallel Trade. PMID- 27201248 TI - State of the Art Research In Austria: Dexhelpp - Decision Support For Health Policy and Planning: Methods, Models and Technologies Based On Existing Health Care Data. PMID- 27201250 TI - Patient's Participation in Improvement of Health Related Outcomes: The Better Care Plan. PMID- 27201249 TI - Access To Orphan Drugs in France: The Case Of Siklos For The Treatment of Sickle Cell Syndrome Before The Council of State. PMID- 27201251 TI - The Risk of Metabolic Disorders in Patients Treated with Asenapine or Olanzapine: A Real World Data Study Conducted in Italy and Spain. PMID- 27201252 TI - Efficacy of the Phosphorylated Tau P181 for the Alzheimer's Disease Dementia - a Systematic Review and Meta Analysis. PMID- 27201253 TI - Cost and Duration Of Regulatory Process in an Observational Study in Europe and USA. PMID- 27201254 TI - Network Meta-Analysis of the Relative Efficacy of Pharmacological and Psychological Interventions in Adults with Obsessive Compulsive Disorder. PMID- 27201255 TI - Adaptive Video Games can Assess and Enhance Cognitive Health. PMID- 27201256 TI - Systematic Literature Review and Mixed Treatment Comparison of Gxr Versus other Treatments in Children and Adolescents with Attention Deficit Hyperactivity Disorder (ADHD). PMID- 27201257 TI - An Evaluation of the Comparative Effectiveness of Clomethiazole Against Diazepam in the Treatment of Alcohol Withdrawal Syndrome in Routine Clinical Practice. PMID- 27201258 TI - Predictors Pf Remission in the Treatment of Depression in the Middle East: Real World Evidence From A 6-Month Prospective Observational Study. PMID- 27201259 TI - Relationship of Insight with Medication Adherence and the Impact on Outcomes in Patients with Schizophrenia and Bipolar Disorder: Results From A 1-Year European Outpatient Observational Study. PMID- 27201260 TI - The Quality of Prescribing for Psychiatric Patients. PMID- 27201261 TI - Systematic Review and Mixed Treatment Comparison of Lithium or an Atypical Anti Psychotic (AAP) used to Augment a Selective Serotonin Reuptake Inhibitor (SSRI) in Treatment Resistant Depression (TRD). PMID- 27201262 TI - The Prevalence and Disease Burden of Treatment-Resistant Depression - a Systematic Review of the Literature. PMID- 27201263 TI - Social Contacts Reduce Negative Symptoms, Especially Emotional Withdrawal in Patients with Schizophrenia. PMID- 27201265 TI - Costs of Employees with Treatment-Resistant Depression Based on a Canadian Private Claims Database. PMID- 27201264 TI - Outpatient Treatment of Adolescents in Japan with Drugs for Attention Deficit Disorders. PMID- 27201266 TI - Treatment Cost Comparison: Paliperidone Palmitate Versus Risperidone Long Acting in Brazil. PMID- 27201267 TI - Analysis of 'Revolving Door' Patients in Opioid Dependent Patients: the Impact of Treatment Discontinuation on Relapse Rates and Health Care Costs in us Public Health Insurance Claims. PMID- 27201268 TI - The Potential Benefits of Long-Acting Atypical Antipsycothic Therapy in Preventing Relapse in Brazil. PMID- 27201269 TI - Prevalence of Metabolic Syndrome in Patients with Schizophrenia According to the Presence or Absence of Negative Symptoms. PMID- 27201270 TI - Aripiprazole Once-Monthly is a Cost-Effective Therapeutic Option in the Maintenance Treatment of Schizophrenia: Results from a Markov Model. PMID- 27201271 TI - Atomoxetine for the Treatment of Newly Diagnosed Adults with Adhd - a Cost Effectiveness Analysis in Spain. PMID- 27201272 TI - Productivity Loss and Resource Utilization in Individuals Providing Care for Adults with Schizophrenia in the 5eu. PMID- 27201273 TI - A Model to Estimate the Health System Burden of Prescription Opioid Abuse in Europe. PMID- 27201275 TI - Medication Usage Pattern, Health Resource Utilization and Economic Burden for Patients with Mdd in Beijing, China. PMID- 27201274 TI - The Societal Costs of Schizophrenia in Switzerland. PMID- 27201276 TI - The Cost Effectiveness of Group Art Therapy for Patients with Non-Psychotic Mental Health Disorders in England And Wales. PMID- 27201277 TI - Paliperidone Versus Atypical Long-Acting Antipsychotics for Relapsed Chronic Schizophrenia: an Economic Analysis. PMID- 27201278 TI - The Effect of Attention-Deficit/Hyperactivity Disorder on Functioning and Resource Utilization by Psychiatric Outpatients in Europe. PMID- 27201279 TI - Economic Evaluation of Nalmefene for the Treatment of Alcohol Dependence in Greece. PMID- 27201280 TI - Prescribing Anti-Depressants by Baseline Severity: Evidence Synthesis, Economic Model and Value of Information Analysis. PMID- 27201281 TI - Cost-Effectiveness of Lithium Versus an Atypical Anti-Psychotic (AAP) used to Augment Treatment with a Selective Serotonin Reuptake Inhibitor (SSRI) in Treatment Resistant Depression (TRD). PMID- 27201283 TI - Cost-Utility Analysis of Long-Acting Paliperidone in Comparison with Oral Risperidone, Oral Paliperidone and Long-Acting Risperidone in the Maintenance Treatment of Schizophrenia in the Czech Republic. PMID- 27201282 TI - Computerised Cognitive Behaviour Therapy for Depression Management: A Cost Effectiveness Analysis. PMID- 27201284 TI - Cost-Utility of Vortioxetine in the Treatment of Major Depressive Disorder: Comparison with Agomelatine, Bupropion, Sertraline and Venlafaxine in the Finnish Setting. PMID- 27201285 TI - Cost-Effectiveness of Paliperidone Palmitate Versus other Antipsychotics for the Treatment of Schizophrenia in France. PMID- 27201286 TI - Which Adverse Effects Influence the Dropout Rate in Selective Serotonin Reuptake Inhibitor (Ssri) Treatment? PMID- 27201287 TI - General Beliefs about Medicines Among Depressed Patients in Saudi Arabia. PMID- 27201288 TI - Adherence to Psychotropic Medications by Outpatients in Psychiatric Hospital, Uselu Benin City, Nigeria. PMID- 27201289 TI - Economic Evaluation of Agomelatine for Major Depressive Disorders Relative to other Antidepressants in the Italian Setting. PMID- 27201290 TI - Retrospective Database Study on Health Care Resource Utilization of Patients Initiating Long-Acting Olanzapine in Sweden. PMID- 27201291 TI - Use of Services and Cost of Agitation and Containment in Psychiatric Hospitals: a Systematic Review. PMID- 27201293 TI - Describing the Health Status of Schizophrenia Caregivers in the 5E.U. PMID- 27201292 TI - Treatment Continuation and Treatment Characteristics of 3 Long Acting Antipsychotic Medications (Paliperidone Palmitate, Risperidone Microspheres and Haloperidol Decanoate) in Belgium. PMID- 27201295 TI - The Anxiety Inventory for Respiratory Disease (Air): an Exploration of the Air's Psychometric Properties Through Rasch Analysis. PMID- 27201294 TI - The Impact on Work and Social Activities Among Carers of Children with Adhd in Sweden Relative to Other Nordic Countries. PMID- 27201296 TI - Conceptual Comprehensiveness of Anxiety Instruments in Chronic Obstructive Pulmonary Disease: Exploring the Potential for Confounding Somatic Items. PMID- 27201298 TI - Quality of Life and the Predictors of Thai Depressive Disorders Patients. PMID- 27201297 TI - Does Giving Carers a Break Improve their Wellbeing? Results from an Evaluation using the EQ-5D-5L. PMID- 27201299 TI - Cultural Adaptation of the Alcohol Quality of Life Scale for Use in Japan, China, and Korea. PMID- 27201300 TI - Alcohol Consumption: the Burden of Entourage. PMID- 27201301 TI - The Patient Experience of Alcohol use Disorder. PMID- 27201302 TI - Societal Costs and Qol of Children with Adhd and their Parents: a Comparison to a Reference Group from the General Population. PMID- 27201303 TI - Quality of Life in Hospitalized Seniors with Psychiatric Disorders. PMID- 27201304 TI - A Potential Gender Bias in the Quality of Life - an Exploratory Standard Gamble Experiment Among Economics Students. PMID- 27201305 TI - Economic Evaluation of Dialectical Behavior Therapy (Dbt) Amongst those with Borderline Personality Disorder (Bpd) who Engage in Self-Harm in Ireland. PMID- 27201306 TI - Work Productivity Loss with Depression, Diagnosed and Undiagnosed, among Employed Respondents in an Internet-Based Survey Conducted in Japan. PMID- 27201307 TI - Comparison of Health Care Resource use and Costs in Patients with Opioid Prescription Drug Dependence (Opd) Treated with Buprenorphine/Naloxone and Patients without Pharmacological Treatment: Retrospective Analysis of us Public Insurance Claims. PMID- 27201308 TI - Description of Agitation and Crisis Interventions in a Psychiatric Hospital in Spain: a Qualitative Study. PMID- 27201309 TI - Drug Utilization Study of Antipsychotics used for the Hospital Treatment Of Schizophrenia in Russia. PMID- 27201310 TI - Antidepressant use and Suicide Rate in England: the Geographic Divide. PMID- 27201312 TI - Utilization Patterns of Antipsychotics Usage in Tertiary Care Hospital Patients with Schizophrenia. PMID- 27201311 TI - Analysis of Prescribing Patterns of Atypical Antipsychotics in Lhu Caserta. PMID- 27201313 TI - Drug Utilization Pattern of Lisdexamfetamine Dimesylate in Germany. PMID- 27201314 TI - Comparison of Resource use and Health Care Costs in New Initiators of Long-Acting Injectable (Lai) and Oral Second Generation Antipsychotics. PMID- 27201315 TI - Economic Burden of Major Depressive Disorder (Mdd) in Five European Countries: Description of Resource use by Health State. PMID- 27201316 TI - The Health Economic Impact of Resource use in Dementia: the Erlanger Dementia Registry (EDR). PMID- 27201317 TI - Maintenance Daily Dose of Venlafaxine and Duloxetine in the Monotherapy of Patients with Major Depressive Disorder Resistant to Selective-Serotonin-Reuptake Inhibitors in Routine Clinical Practice in Spain. PMID- 27201318 TI - The Impact of Economic Crisis on Suicide Rates in Greece. PMID- 27201319 TI - Population Health: Mental Health of us Veterans by Benefits Enrollment Status. PMID- 27201320 TI - Treatment Patterns and Health Care Costs in Patients with Schizophrenia Initiating with First- or Second-Generation Antipsychotic: Results from a Japanese Claims Database Analysis. PMID- 27201321 TI - History of Antidepressant use Among Primary Care Depressed Patients Switching Treatments in the United Kingdom. PMID- 27201322 TI - Treatment Patterns and Health Care Costs in Patients with Depression Treated with Antidepressant only or Combined with Benzodiazepine: Results From a Japanese Claims Database Analysis. PMID- 27201323 TI - Level of Testing for Potential Medication-Related Co-Morbidities for Patients Taking Antipsychotics. PMID- 27201324 TI - Comparative Efficacy And Tolerability Of Solifenacin 5mg Versus Oral Antimuscarinic Agents In Overactive Bladder (Oab): A Systematic Literature Review (Slr) And Mixed Treatment Comparison (Mtc). PMID- 27201325 TI - Comparative Effectiveness Of Automated Versus Continuous Ambulatory Peritoneal Dialysis On Patients With End-Stage Renal Disease In Taiwan. PMID- 27201326 TI - An Economic Model To Investigate The Budget Impact In Spain Of Onabotulinumtoxina To Manage Urinary Incontinence In Patients With Idiopathic Overactive Bladder. PMID- 27201327 TI - A Budget Impact Analysis (Bia) Of The Use Of Paricalcitol For The Treatment Of Secondary Hyperparathyroidism (Shpt) In End Stage Renal Disease Patients. PMID- 27201328 TI - Be Cautious Of Triple Whammy!!! PMID- 27201329 TI - A Study To Assess Disease Progression To Esrd Within A Year In Patients With Advanced Ckd. PMID- 27201330 TI - Analysis Of Budget Impact Of Anemia Correction In Russian Patients With Chronic Kidney Disease. PMID- 27201331 TI - Budget Impact Evaluation Of Treatment With A Low Protein Diet And Ketoanalogues Of Essential Aminoacids For Predialysis Patients In Russian Federation. PMID- 27201333 TI - Cic Users' Preference For Catheters Reducing The Uti Frequency. PMID- 27201332 TI - Cost-Utility And Value Of Information (Voi) Analyses On The Feasibility Of A Future Randomised Controlled Trial (Rct) Of Invasive Urodynamic Testing Prior To Surgery For Stress Urinary Incontinence In Women. PMID- 27201334 TI - A Review Of Cost Of Illness Studies In Patients With End Stage Renal Disease. PMID- 27201336 TI - The Impact Of Cardiovascular Disease And Type 2 Diabetes Mellitus On Social Cost In Chronic Kidney Disease Patients In Italy. PMID- 27201335 TI - The Economic Cost Of Urinary Tract Infections In The Community: Results From Ireland. PMID- 27201337 TI - Cost Consequence Analysis Of Darbepoetin Alfa For The Treatment Of Anemia Due To Chronic Kidney Disease (Ckd) In Greece. PMID- 27201338 TI - Cost Effectiveness Of Extracorporeal Shock Wave Lithotripsy Against Ureteroscopic Laser Lithotripsy For Treatment Of Ureteral Calculi. PMID- 27201339 TI - Cost Effectiveness Of Solifenacin Compared With Oral Antimuscarinic Agents For The Treatment Of Patients With Overactive Bladder (Oab) In The Uk. PMID- 27201340 TI - Cost-Effectiveness Of Mycophelonate Sodium On Patients With Renal Transplant At The Public Mexican Health Care System. PMID- 27201341 TI - Economic Evaluation Of Percent Free Psa For Prostate Cancer Detection In Taiwanese Men. PMID- 27201342 TI - Cost-Effectiveness Of Mirabegron 50mg Compared To Tolterodine Er 4mg In The Treatment Of Patients With Overactive Bladder In Canada. PMID- 27201343 TI - Early Versus Late Ketoanalogs Supplementation In Patients With Chronic Kidney Disease In Taiwan - A Cost-Effectiveness Analysis. PMID- 27201344 TI - COST- MINIMIZATION ANALYSIS OF THE DIRECT COSTS OF SEVELAMER CARBONATE AND LANTHANUM CARBONATE IN THE TREATMENT OF CKD-ND PATIENTS. PMID- 27201345 TI - A Spanish Cost-Effectiveness Analysis Of Sevelamer Versus Calcium Carbonate In Nondialysis-Dependent Chronic Kidney Disease (Ckd) Patients. PMID- 27201346 TI - Burden On Secondary Care Of Overactive Bladder Patients Who Are Inadequately Managed With Anticholinergics In England. PMID- 27201347 TI - A Cost-Effectiveness Analysis Of Onabotulinumtoxina Verse. Best Supportive Care (bsc) For The Treatment Of Anticholinergic Treatment-Refractory Neurogenic Detrusor Overactivity (ndo). PMID- 27201348 TI - Cost-Effectiveness Comparison Of Botulinum Toxin Type A Plus Best Supportive Care Versus Best Supportive Care Alone In The Treatment Of Idiopathic Overactive Bladder With Urinary Incontinence Among Patients Not Adequately Managed By Anticholinergic Therapy In France. PMID- 27201349 TI - Persistence And Adherence With Mirabegron, A New Beta-3 Receptor Agonist, Versus Antimuscarinics In Overactive Bladder: Early Experience In Canada. PMID- 27201350 TI - Accept(r) Questionnaire: Relation Between Acceptance And Compliance In Liver- And Kidney-Transplanted Patients Converted To Once-Daily Tacrolimus. PMID- 27201351 TI - Treatment Discontinuation In Patients With Urinary Incontinence Suffering From Glaucoma. PMID- 27201352 TI - Health-Related Quality Of Life (Hrqol) Of Asian Patients With End-Stage Renal Disease (Esrd) In Singapore. PMID- 27201353 TI - Health-Related Quality Of Life And Subjective Happiness Of Patients With Benign Prostatic Hyperplasia: First Results Of A Cross-Sectional Survey From Hungary. PMID- 27201354 TI - Men's Preferences For The Treatment Of Lower Urinary Tract Symptoms (Luts) Associated With Benign Prostatic Hyperplasia (Bph): A Discrete Choice Experiment (Dce). PMID- 27201355 TI - Incidence Of Unlicensed And Off-Label Prescription In Urologic Cancers Therapy In Turkey: Assessment Of Legislative And Regulatory Policy. PMID- 27201356 TI - Readmittance To Hospital Within 6 Months After A Venous Thromboembolism Event: Prefer In Vte Registry. PMID- 27201357 TI - A Mixed Methods Approach (Mma) To Understanding Men's Attitudes Toward The Management Of Lower Urinary Tract Symptoms (Luts) Associated With Benign Prostatic Hyperplasia (Bph). PMID- 27201358 TI - Prevalence Of Symptoms And Cluster Analysis In Dialysis Patients Using Kdqol-36. PMID- 27201359 TI - Clotting Factor (Cf) Product Use And Same-Day Risk For Thrombotic Adverse Events (Tes), As Recorded In Large Health Care Database During 2008-2013 Study Period. PMID- 27201360 TI - Development Of A Collaborative European Pharmacoepidemiologic Post-Authorization Safety Study (Pass) Programme Examining Rivaroxaban Use In Routine Clinical Practice. PMID- 27201361 TI - The Effect Of Atriala Fibrillation In Acute Myocardial Infarction Patients In Taiwan. PMID- 27201362 TI - The Additional Costs Of Clinical Complications In Patients Undergoing Transcatheter Aortic Valve Replacement In The German Health Care System. PMID- 27201363 TI - Discontinuation And Hospitalisation Rates In Patients With Atrial Fibrillation: Follow-Up Results Of The Prefer In Af Registry. PMID- 27201364 TI - Coronary And Cardiovascular Disease Risks In Migraine Patients: Evidence From National Health And Nutrition Examination Survey 1999-2004. PMID- 27201365 TI - Effectiveness And Costs Of Different Strategies For The Diagnosis Of Stable Coronary Artery Disease Results From The Evinci Study. PMID- 27201366 TI - An Assessment Of The Current Literature On Apheresis Use In The Treatment Of Familial Hypercholesterolemia. PMID- 27201367 TI - Estimated Added Benefit Of Catheter-Based Renal Denervation For Moderate Treatment-Resistant Hypertension: Impact Of Age And Cardiovascular Risk Factors. PMID- 27201368 TI - The Use Of Minimally Invasive Surgery (Mis) And Intraoperative Imaging Modalities In The Treatment Of Intracerebral Hemorrhage (Ich): A Systematic Review Of The Literature. PMID- 27201369 TI - Pharmacoeconomic Grounding Of Using Polypill Amlodipine With Atorvastatin Versus Monodrugs In Patients With Hypertension And Dyslipidemia In Ukraine. PMID- 27201370 TI - Lifetime Clinical Events Avoided And Resource Utilization With Apixaban Compared To Low-Molecular-Weight Heparin Followed By A Vitamin K Antagonist For The Treatment And Prevention Of Venous Thromboembolism. PMID- 27201371 TI - The Effectiveness Of Carotid Artery Stenting Compared With Endarterectomy In Symptomatic Patients With Carotid Stenosis In Korean Multi-Center Setting. PMID- 27201372 TI - Real-Time Assessment Of Medication Taking And Activities Of Daily Living In Patients With Uncontrolled Hypertension. PMID- 27201373 TI - Use Of Computer Simulation To Generate Evidence To Aid Health Care Decision Making: An Example Using The Archimedes Model To Compare Rosuvastatin With Atorvastatin. PMID- 27201374 TI - Critical Appraisal Of Network Meta-Analyses Evaluating The Efficacy And Safety Of New Oral Anticoagulants In Atrial Fibrillation Stroke Prevention Trials. PMID- 27201375 TI - Targeted Literature Review Of Unmet Need In The Hyperlipidaemia Population With High Risk Of Cardiovascular Disease. PMID- 27201376 TI - Study On Drug Utilization And Assessment Of Stroke Risk Using Chads2 And Cha2ds2 Vasc Scoring In Elderly Patients With Non-Valvular Atrial Fibrillation. PMID- 27201377 TI - Management Of Chronic Thromboembolic Pulmonary Hypertension: Clinical And Reported Outcomes From A Referral Hospital In Spain. PMID- 27201378 TI - The 3.5-Year Mortality Impact Of Drugs In Secondary Prevention Of Myocardial Infarction In Real-Life (Interim Analysis Of The Eole Cohort). PMID- 27201379 TI - A Database Analysis Of Patients Eligible For Second-Line Lipid-Lowering Treatment For Hypercholesterolaemia In England. PMID- 27201380 TI - More Than One In Two Instances Of Venous Thromboembolism (Vte) Treated In French Hospitals Could Have Occurred During The Hospital Stay. PMID- 27201381 TI - Real World Incidences And Hospital Cost Of Venous And Pulmonary Thromboembolic Events In France. PMID- 27201383 TI - Retrospective Analysis On Hospitalization And Health Care Costs, According To Serum Uric Acid Levels In Patients From A Sample Of Italian Local Health Units. PMID- 27201382 TI - Cognitive Function And Non-Adherence To Antihypertensive Medications. PMID- 27201384 TI - Risk Factors Associated With Venous Thromboembolism Recurrence In A European Population. PMID- 27201385 TI - A Retrospective Study Of Mortality In Risk Patients With High Dose Statin Usage And No Statin Usage. PMID- 27201386 TI - The Association Between The Nature And Timing Of Dental Visits And C-Reactive Protein Levels. PMID- 27201387 TI - Traditional And Non-Traditional Risk Factors For Cardiovascular Disease In Type 2 Diabetes: Systematic Review Of Longitudinal Studies. PMID- 27201388 TI - Relation Of The Time In Therapeutic Range (Ttr) Of Warfarin To Bleeding Incidences In Patients With Atrial Fibrillation. PMID- 27201389 TI - Statin Use And Risk Of Developing Diabetes In Cardiovascular Disease: Systematic Literature Review And Meta-Analysis. PMID- 27201390 TI - Budgetary Impact Analysis Of Reimbursement Varenicline In The Smoking Cessation Treatment Of Patients With Cardiovascular Diseases, Chronic Obstructive Pulmonary Disease Or Type-2 Diabetes Mellitus: A National Health System Perspective In Spain. PMID- 27201391 TI - The Budget Impact Of New Generation Ct Scanners For Difficult-To-Image, Low-Risk Patients With Suspected Cad. PMID- 27201392 TI - Budget Impact Analysis Of Botulinum Toxin A Therapy For Upper Limb Spasticity In Germany. PMID- 27201394 TI - Simvastatin Plus Fenofibrate As A Fixed Dose Combination In The Treatment Of Mixed Dyslipidemia In Greece: Budget Impact Analysis. PMID- 27201393 TI - Budget Impact Analysis Of Apixaban Versus Other Noacs For The Prevention Of Stroke In Italian Non-Valvular Atrial Fibrillation Patients. PMID- 27201395 TI - Budget Impact Analysis Of Hypertensive Treatment With Indapamide And Amlodipine Single-Pill Combination In The Polish Setting. PMID- 27201396 TI - Modeling The Impact Of A Digital Health Feedback System In Uncontrolled Hypertensive Patients. PMID- 27201398 TI - The Move Towards Full Implementation Of The Nice Guidelines For Stroke Prevention In Atrial Fibrillation: The Potential Cost And Clinical Impact. PMID- 27201397 TI - Estimating The Value Of Cangrelor From Eliminating Preloading In Coronary Artery Bypass Graft (Cabg) Patients. PMID- 27201399 TI - Renal Denervation With The Symplicity Catheter System For Treatment-Resistant Hypertension: A Budget Impact Analysis. PMID- 27201400 TI - Dabigatran verse. Dicoumarins In Non-Valvular Atrial Fibrillation. Budget Impact Study In The Extremadura Public Health System. PMID- 27201401 TI - Budget Impact Of The Introduction Of New Oral Anticoagulants (Noac) For No Valve Atrial Fibrillation (Nvaf) In Extremadura. PMID- 27201402 TI - Cost Estimation Of Home Blood Pressure Monitoring Versus Combined Office And Ambulatory Measurements In Hypertension Management. PMID- 27201403 TI - Cost Effectiveness Analysis Of Mitraclip In Mitral Regurgitation For High Risk Patients. PMID- 27201404 TI - Comparing Actual Patient Level Hospital Costs To The Canadian Cmg+ Costing Estimates For Acute Myocardial Infarction. PMID- 27201405 TI - Cost-Effectiveness And Budget Impact Analyses Of Risk Stratification Of Patients With Moderate Risk Of Cardiovascular Events Using Lp-Pla2 Testing. PMID- 27201406 TI - Goal Directed Perfusion (Gdp): A Differential Cost Analysis In Uk And Us. PMID- 27201407 TI - The Cost Comparison Of Drug-Eluting Stents (Des) And Bare-Metal Stents (Bms) - A Retrospective Cohort Matched Study. PMID- 27201408 TI - Study Of Costs Of The Cardiac And Diabetes Mellitus Patient In A Cardiology Hospital Of High Complexity. PMID- 27201409 TI - A Cost Comparison Analysis Of Medtronic's Stent Graft System To Competition For Endovascular Aneurysm Repair For Abdominal Aortic Aneurysms. PMID- 27201410 TI - Can A Cvd Polypill Save Money In The 'Real World'? PMID- 27201411 TI - Economics And Clinical Evaluation Of Endovascular And Surgical Treatment Of Patients With Disability Of Superficial Femoral Artery. PMID- 27201412 TI - Hospitalizations And Costs In Patients With Implantable Cardioverter Defibrillators: Association Of Long Verse Standard Detection Intervals. PMID- 27201413 TI - Interest Of A Hospital Database To Analyze The Cost For Acute Stroke: The Example Of Versailles Hospital. PMID- 27201414 TI - Burden Of Cardiovascular Complications In Patients With Atrial Fibrillation In France. PMID- 27201415 TI - Cost Of Bleeding In Complex Cardiac Surgery. PMID- 27201416 TI - Clnical Management Of Non-Valvular Atrial Fibrillation In Hong Kong. PMID- 27201417 TI - The Cost Burden Of Syncope At A Hospital Level In Spain. PMID- 27201418 TI - The Economic Impact Of Cardiovascular Events In Patients Post Myocardial Infarction: Uk Health Care Perspective. PMID- 27201419 TI - Cost Of Bleeding In Trauma Patients. PMID- 27201420 TI - Cost Of Illness: Heart Failure In Ireland. PMID- 27201422 TI - Pharmacoeconomic Burden Of Statins In Patients With Ischemic Heart Disease In The Health Care Of Belarus. PMID- 27201421 TI - The Cost Of Illness Of Atrial Fibrillation In Italy: A Cohort Of Hospitalized Patients. PMID- 27201423 TI - A Systematic Review Of Cost-Of-Illness Studies In Chronic Heart Failure. PMID- 27201424 TI - The Costs Of Atherosclerotic And Haemorrhagic Events Associated With Acute Coronary Syndrome (Acs) In Turkey. PMID- 27201425 TI - Does A 12-Lead Ecg More Reliably Detect Atrial Fibrilation Than A Rhythm Strip Only Ecg? PMID- 27201427 TI - Annual Cost Of Conservative Treatment Of Supraventricular Tachycardias In Poland. PMID- 27201426 TI - Linking Health Care Administrative Databases And National Registry Data In Order To Monitor Icd Therapy In Italy. PMID- 27201429 TI - Hospital Costs Of Ischemic Stroke And Transient Ischemic Attack In The Netherlands. PMID- 27201428 TI - Costs Of Treating Cardiovascular Events In Germany: A Systematic Literature Review. PMID- 27201430 TI - The Economic Impact Of Hypertension In Health Care System Of Pakistan. PMID- 27201431 TI - Cost-Effectiveness Of Dabigatran Compared With Warfarin, Apixaban, Rivaroxaban And Low Molecular Weight Heparins For The Treatment And Secondary Prevention Of Venous Thromboembolism In Colombia. PMID- 27201432 TI - Economic Evaluation Of Ferric Carboxymaltose In Patients With Chronic Heart Failure And Iron Deficiency: An Analysis For Greece Based On Fair-Hf Trial. PMID- 27201433 TI - Potential Cost-Effectiveness Of Therapeutic Drug Monitoring In Patients With Resistant Hypertension. PMID- 27201434 TI - Cost-Effectiveness Analysis Of Ivabradine In Heart Failure With Reduced Left Ventricular Ejection Fraction In Spain. PMID- 27201435 TI - Pharmacoeconomic Assessment Of Apixaban Versus Standard Of Care For The Prevention Of Stroke In Italian Non-Valvular Atrial Fibrillation Patients. PMID- 27201436 TI - Cost Consequence Comparison Of Hemostatic Matrix Agents. PMID- 27201437 TI - Cost-Effectiveness Analysis Of Ticagrelor In Treating Patients With Acute Coronary Syndrome In Hong Kong. PMID- 27201438 TI - Cost-Effectiveness Of Ranolazine For The Treatment Of Angina Pectoris In Russia. PMID- 27201439 TI - Assessing The Cost Effectiveness Of An Anticoagulation Clinic In Comparison With The Usual Medical Clinic In Kuala Lumpur Hospital. PMID- 27201440 TI - The Cost Of Increasing Physical Activity And Decreasing Body Mass Index For Mid Life African Women. PMID- 27201441 TI - Cost Effectiveness Analysis Of Apixaban Versus Other Noacs For The Prevention Of Stroke In Italian Non-Valvular Atrial Fibrillation Patients. PMID- 27201442 TI - Cost Effectiveness Of Ivabradine In Chronic Heart Failure Patients With Heart Rate Above Bpm In Taiwan. PMID- 27201443 TI - Cost-Effectiveness Of Apixaban Compared To Other Anticoagulants For Lifetime Treatment And Prevention Of Recurrent Venous Thromboembolism. PMID- 27201444 TI - Novel Imaging Technology To Select Patients For Individualized Therapies: Test Performance And Cost-Effectiveness. PMID- 27201445 TI - Cost-Effectiveness Of Extracorporeal Cardiopulmonary Resuscitation In Patients With Refractory Cardiac Arrest. PMID- 27201446 TI - Economic Analysis Of Thrombo Incode, A Clinical-Genetic Function For Assessing The Risk Of Venous Thromboembolism. PMID- 27201448 TI - The Cost-Effectiveness Of Dabigatran Etexilate Compared With Warfarin And Rivaroxaban In The Treatment Of Acute Pulmonary Embolism In The Uk. PMID- 27201447 TI - A Cost-Effectiveness Analysis Of Interventions For Symptomatic Varicose Veins. PMID- 27201449 TI - The Cost-Effectiveness Of Dabigatran Etexilate Compared With Rivaroxaban In The Treatment Of Acute Venous Thromboembolism In The Uk. PMID- 27201450 TI - Cost-Effectiveness Of Apixaban Compared To Warfarin And Aspirin In Patients With Non-Valvular Atrial Fibrillation (Nvaf) In The Russian Federation. PMID- 27201451 TI - The Cost-Effectiveness Of Dabigatran Etexilate Compared With Warfarin In The Treatment And Secondary Prevention Of Acute Venous Thromboembolism In The Uk. PMID- 27201453 TI - Cost Model Analysis Of Gore(r) Propaten(r) Vascular Graft Verse. Standard Eptfe Vascular Graft For Infrapopliteal Bypass In Peripheral Arterial Disease (pad) Management: Spanish Scenario. PMID- 27201452 TI - Economic Evaluation Of Valsartan Versus Olmesartan Addition To Amlodipine And Hydrochlorothiaziade Single-Pill Triple Antihypertensive Therapy. PMID- 27201454 TI - Impact Of A Pharmacological Cardioversion With Vernakalant On The Management Cost Of Recent Atrial Fibrillation In Belgium. PMID- 27201455 TI - Cost-Effectiveness Of High-Sensitive Troponin Assays For The Early Rule-Out Or Diagnosis Of Acute Myocardial Infarction (Ami) In People With Acute Chest Pain: A Nice Diagnostic Assessment. PMID- 27201456 TI - Efficiency Of Rehabilitation Programs For Patients After Traumatic Brain Injury And Acute Cerebrovascular Accident (Stroke) In Russia. PMID- 27201457 TI - Cost Effectiveness Of Renal Denervation Therapy For The Treatment Of Resistant Hypertension In The Netherlands. PMID- 27201458 TI - Burden Of Hyperlipidemia Resulting From Productivity Loss - Estimates From Population-Based Register Data In Sweden. PMID- 27201459 TI - Cost-Utility Analysis Of Carotid Artery Stenting Versus Endarterectomy For Symptomatic Carotid Stenosis Patients. PMID- 27201460 TI - Cost Effectiveness Analysis Of Ticagrelor Versus Generic Clopidogrel In The Treatment Of Patients With Acute Coronary Syndrome In Spain. PMID- 27201461 TI - Cost-Effectiveness Of Ldl-P-Guided Statin Therapy. PMID- 27201463 TI - Cost-Utility Analysis Of Hypertensive Treatment With Indapamide And Amlodipine Single-Pill Combination In The Polish Setting. PMID- 27201462 TI - Pharmacoeconomic Analysis Of Rosuvastatin Use In Patients With Hypercholesterolemia In The Health Care Of Belarus. PMID- 27201464 TI - Understanding Medication Adherence Using Stated-Preference Data. PMID- 27201465 TI - Health Behavior And Medication Adherence. PMID- 27201466 TI - Clinical Pathway And Health Care Resources Utilization Of A Patients Cohort At High Risk Of Cardiovascular Disease Of Local Health Care Unit (Asln degrees 1) Of Milan: A Results Of Intervention On Secondary Prevention. PMID- 27201468 TI - Health Care Costs Associated With Cardiovascular Events In Patients With Hyperlipidemia - Estimates From Population-Based Register Data In Sweden. PMID- 27201467 TI - Inpatient Case-Related Treatment Costs For Different Cardiovascular Diseases In Germany. PMID- 27201469 TI - Cardiovascular Risk, Gender And Medication Adherence In Rural Area Of Vietnam. PMID- 27201470 TI - Health State Utilities In Chronic Heart Failure In The Uk. PMID- 27201471 TI - Health State In Patients With Venous Thromboembolism On Conventional And Non-Vka Oral Anticoagulants As Assessed With The Eq-5d-5l Questionnaire: Prefer In Vte Registry. PMID- 27201472 TI - Health State In Patients With Atrial Fibrillation On New Oral Anticoagulants As Assessed With The New Eq-5d-5l Questionnaire At Baseline And 12-Month Follow-Up: Prefer In Af Registry. PMID- 27201473 TI - Acute And Chronic Impact Of Cardiovascular Events On Health State Utilities. PMID- 27201474 TI - Patient Adherence Among Adolescents With Arterial Hypertension. PMID- 27201475 TI - Sensitivity Of The Safuca Questionnaire To Detect Differences Between Atrial Fibrillation Patients Treated With Vitamin-K Antagonist Against Those Treated With New Oral Anticoagulants. PMID- 27201476 TI - Unmet Needs And Solutions For Heart Failure Admission. PMID- 27201477 TI - Clinical Psychologists: Closing The Communication Gap Between Physicians And Patients, Leading To Higher Patient Satisfaction And Compliance. PMID- 27201478 TI - Evaluating The Gap Between Physicians' And Patients' Understanding Of Patient Needs. PMID- 27201479 TI - The Intermediate Burden Of Diabetes Mellitus In Patients With Cardiovascular Disease (Cvd): A Quality Adjusted Life Year (Qaly) -Analysis Based On Primary Longitudinal Data. PMID- 27201481 TI - Uisess-B Oral Health Questionnaire Validity And Reliability In A Mexican Diabetic, Systemic Hypertension And Obese Patients. PMID- 27201480 TI - Beliefs About Medicines In An Urban Black Hypertension Population. PMID- 27201482 TI - The "Venous Age": A New Tool To Sensitize Patients To Their Venous Disease. PMID- 27201483 TI - Preferences Regarding The Attributes Of Oral Anticoagulants In Patients With Atrial Fibrillation Results Of A Discrete Choice Experiment. PMID- 27201484 TI - Health Related Quality Of Life At One Year Post Discharge In Patients With Heart Failure. PMID- 27201485 TI - Literature Review Of Pro Measures Assessing Anticoagulant Therapy. PMID- 27201486 TI - Place Of Residence And Employment Status After Stroke. PMID- 27201487 TI - Treatment Patterns And Quality Of Life Of Patients With Non-Valvular Atrial Fibrillation: An Experience Of A Tertiary Health Care Centers (Treq-Af Study). PMID- 27201488 TI - Quality Of Life In Patients With Permanent Cardiac Pacemaker In The Slovak Republic. PMID- 27201489 TI - The Evaluation Of The Health Related Quality Of Life Among Adults With Hypertension. PMID- 27201490 TI - Treatment Satisfaction In Patients With Venous Thromboembolism As Measured With Pact-Q2: Prefer In Vte Registry. PMID- 27201492 TI - Health Utility Of Acute Coronary Syndrome Patients From An Asian Population. PMID- 27201491 TI - Health-Related Quality Of Life Impact Of Triple Combinations Of Olmesartan Medoxomil, Amlodipine Besylate And Hydrochlorothiazide In Subjects With Hypertension. PMID- 27201494 TI - The Clinical Impact Of Rivaroxaban To Chinese At Atrial Fibrillation Patients Results From A Simple Communication Tool. PMID- 27201493 TI - The Clinical Impact Of Rivaroxaban To Chinese At Deep Vein Thrombosis Patients Results From A Simple Communication Tool. PMID- 27201496 TI - Primary Pacemaker Insertion: Gender Differences In Prior Er Utilization. PMID- 27201495 TI - Ldl-C Goal Attainment In Patients With Hyperlipidemia - Estimates From Population Based Register Data In Sweden. PMID- 27201497 TI - Treatment Satisfaction In Patients With Atrial Fibrillation On New Oral Anticoagulants As Assessed With Pact-Q2 At Baseline And 12-Month Follow-Up: Prefer In Af Registry. PMID- 27201498 TI - The Impact Of Pharmaceutical Policies On Pharmaceutical Sales Patterns In Sweden And Japan. PMID- 27201499 TI - Assessment Of The Impact Of Legislation On The Utilization Of Statins In Slovakia. PMID- 27201500 TI - Impact Laws And Decrees On Activities: The Ilda Study. PMID- 27201501 TI - Segmentation Is A Key Strategic Tool For Effective Prioritisation And Targeting Of Payers In Highly Competitive Markets; A Client's Perspective. PMID- 27201502 TI - Comparing Quality Effects Of Patient Care In Integrated And Regular Care For Patients With Hypertension. PMID- 27201503 TI - Cost-Effectiveness Of Disease Management Programs For Cardiovascular Risk And Copd In The Netherlands. PMID- 27201504 TI - Analysis of Cardiac Implants Recalls in the Last Decade: An International Comparison. PMID- 27201505 TI - Dabigatran Users With Non-Valvular Atrial Fibrillation in the Us: A Characterization of Dabigatran Initiators and Switchers. PMID- 27201506 TI - Impact of Drug Policy Regulations on the Consumption of Antihypertensive Drugs in Slovakia. PMID- 27201507 TI - Initiation of Oral Anticoagulant Drugs: Identification of Drivers of Prescribing of New Agents Versus Warfarin. PMID- 27201508 TI - The Impact of Modifications of the Formula for Generic Drug Prescription Rate on the Switch To New Brand-Name Drugs With Similar Therapeutic Uses. PMID- 27201509 TI - Local Variation in Primary Care Prescribing Behavior in England: Ticagrelor. PMID- 27201510 TI - The Impact of Drug Policy on the Utilization of Medicines for Treatment of Cardiovascular Diseases in Slovak Republic. PMID- 27201511 TI - Implementation of an Automatic Laboratory Data Checking System To Reduce Deduction of Statins Reimbursement in A Teaching Hospital in Taiwan. PMID- 27201512 TI - Clinical and Demographics Characteristics of Non-Valvular Atrial Fibrillation Patients Switching From Warfarin To Novel Oral Anticoagulants. PMID- 27201513 TI - Investment Aspects of Generic Drug Policies in Countries With Severe Resource Constraints. PMID- 27201514 TI - Drug Utilisation in Cardiovascular Diseases Management in Slovakia: 8 Years Overview. PMID- 27201515 TI - Catastrophic Health Expenditures and Chronic Condition Patients in Greece. PMID- 27201516 TI - Challenges and Opportunities in The Management of Chronic Diseases During The Economic Crisis In Greece: A Qualitative Approach. PMID- 27201517 TI - The Determinants of Uptake and Diffusion of Innovative Health Technologies. An Empirical Analysis. PMID- 27201518 TI - Determinants of Health Care Utilization in Hypertensive Patients: A Longitudinal Analysis. PMID- 27201519 TI - Treatment Patterns in Hyperlipidemia Patients With New Cardiovascular Events - Estimates From Population-Based Register Data in Sweden. PMID- 27201520 TI - Optimizing Process Efficiency Through Implanting Reveal Linq Verse Reveal Xt/Dx From Three Spanish Hospital Perspective. PMID- 27201521 TI - The Association of Hosptial Type and Stroke Centre With Mortality, Length of Stay and Hospital Cost of Ischemic Stroke Patients in Alberta. PMID- 27201522 TI - Regional Variation in Hospital Mortality, Length of Stay and Cost of Ischemic Stroke Patients in Alberta. PMID- 27201523 TI - Snapshot of Prescribing Practice for Clopidogrel and Esomeprazole Co-Prescription and Cost Evaluation of Guidelines Application. PMID- 27201525 TI - Recruiting Cardiologists and Chronic Heart Patients From A Managed Physician Panel To Support Clinical Studies Phase Iii/Iv Or Health Outcome Studies. PMID- 27201524 TI - In-Patient Hospital Costs of Stroke: A Focused Literature Review. PMID- 27201526 TI - Launching Novel Class Iii Implantable Cardiac Devices for Cardiology in Europe First, Is This Common Commercial Practice Improving Health Care Quality for Europeans. PMID- 27201527 TI - Acute Ischemic Stroke (Ais) Patient Management in French Stroke Units and Impact Estimation of Thrombolysis On Care Pathways and Associated Costs. PMID- 27201528 TI - Knowledge Transfer Gap Between Cardiologists and Patients Undergoing Percutaneous Coronary Intervention Regarding Risks Associated With Drug-Eluting Stents: An Asian & European Survey. PMID- 27201529 TI - Health Care Stakeholders' Evaluation of A User-Friendly Tool Which Estimates Long Term Health Gains Following the Reduction of Ldl Levels. PMID- 27201530 TI - Effect of Oral Nutritional Supplements On Hospital Outcomes in Patients Aged 65+ With Congestive Heart Failure. PMID- 27201531 TI - Logistics of Monitoring of Vitamin K Antagonists in Western European Countries: Prefer in Vte Registry. PMID- 27201532 TI - Treatment Patterns and Health Resource Utilization Among Atrial Fibrillation Patients in United Arab Emirates and Saudi Arabia. PMID- 27201533 TI - Ldl-C Lowering Efficacy of Evolocumab (Amg 145) Could Reduce Apheresis in Patients At High Risk for Cardiovascular Events in Germany. PMID- 27201534 TI - Pattern of Benzodiazepines Utilization In Outpatients With Hypertension in Serbia. PMID- 27201535 TI - Treatment Patterns Among Heart Failure Patients Within 30 Days Post Diagnosis: Results From A Us Claims Database Analysis. PMID- 27201536 TI - Predictive Validity of Inappropriate Prescribing Criteria for Adverse Drug Events, Hospitalizations, and Emergency Department Visits: A Time-To-Event Comparison of the Beers and Stopp Criteria. PMID- 27201537 TI - Current Situation of Paediatric and Adult Patients With Fragile X Syndrome: Preliminary Data From the Explain Fxs Registry. PMID- 27201538 TI - Feasibility of A Network Meta-Analysis in Endometriosis. PMID- 27201539 TI - The Efficacy of Oximes in Acute Human Organophosphorus Poisoning; An Updated Meta Analysis. PMID- 27201540 TI - labour induction with prostaglandins: what works best? A systematic review, network meta-analysis and cost-effectiveness analysis. PMID- 27201541 TI - Prevalence of Chronic Diseases Among Older Patients (>65 Years) in German General Practitioner Practices. PMID- 27201542 TI - Economic Assessment of Preeclampsia: Screening, Diagnosis, Treatment Options, and Long Term Outcomes, A Systematic Review. PMID- 27201543 TI - Effects of A Multidisciplinary Home-Based Medication Review Program On Hospital Admissions In Older Adult Singaporeans. PMID- 27201544 TI - Over the Counter Medication and Dietary Supplements Use Among Older Adults. PMID- 27201546 TI - Potential Efficency and Cost Savings To the English Nhs By A Laparoscopic Aproach To Total Abdominal Hysterectomy. PMID- 27201545 TI - Identifying Potentially Inappropriate Medication (Pim) and Major Risk Factors for Hospitalization for Elderly Patients Admitting To Teaching Hospital: Study From Indian Perspective. PMID- 27201547 TI - Examination of the Efficiency of Electrical Stimulation in Case of Stress and Urge Incontinence. PMID- 27201549 TI - Epidemiological and Financial Burden of Preterm Labor Hospitalizations - An Analysis of German Claims Data. PMID- 27201548 TI - Incidence and Long-Term Cost of Oral Steroid-Related Adverse Events in Chronic Diseases in Poland. PMID- 27201550 TI - Burden and Cost of Multiple Chronic Diseases in A Large Cohort of Elderly in Italy. PMID- 27201551 TI - The Prevalence and Cost of Illness in Women With Endometriosis in Ukraine. PMID- 27201552 TI - Malnutrition in Institutionalized and Community-Dwelling Older Adults in Spain: Estimates of Its Costs To the National Health System. PMID- 27201553 TI - Price Variation in Obstetrical Services in A Rural State. PMID- 27201554 TI - Cost Effectiveness Analysis of A Vaccination Programme for the Prevention of Herpes Zoster and Post-Herpetic Neuralgia in Adults Aged 65 and Over in Norway. PMID- 27201555 TI - Misoprostol Vaginal Insert Pharmacoeconomic Model for 5 European Countries. PMID- 27201556 TI - Cost-Benefit Model of Varying Nexplanon and Other Long-Acting Reversible Contraceptive (Larc) Methods: Uptake Compared to the Oral Contraceptive Pill: UK Perspective. PMID- 27201557 TI - Cost-Effectiveness Analysis of Use of Dydrogesterone in Premenstrual Syndrome. PMID- 27201558 TI - Potentially Inappropriate Medication in the Elderly - Relevance and Economics of the 30 Top-Selling Priscus Agents in Germany. PMID- 27201559 TI - A Cost-Effectiveness Analysis of Different Types of Labor for Singleton Pregnancy - Real Life Data. PMID- 27201560 TI - Cost Effectiveness of Pentavalent Rotavirus Vaccine (Rv5) in Slovenia. PMID- 27201561 TI - Health Economic Model On the Costs and Effects of Rotavirus Vaccination in Romania. PMID- 27201562 TI - Cost-Effectiveness Analysis of Coffee Consumption for Prevention of All-Cause Mortality in Germany. PMID- 27201563 TI - Cost-Effectiveness Analysis of Screening Syphilis Among Pregnant Women. PMID- 27201564 TI - Cost-Effectiveness Analysis of Surgical Management of Stress Urinary Incontinence With Single-Incision Mini-Sling Versus Tension-Free Vaginal Obturator in Spain. PMID- 27201565 TI - Cost Effectiveness of Calcium Supplement in Reducing Preeclampsia-Related Maternal Mortality. PMID- 27201566 TI - Economic Evaluation of Ulipristal Acetate for the Treatment of Patients With Moderate and Severe Symptoms of Uterine Fibroids in Romania. PMID- 27201567 TI - The Cost-Effectiveness of Emergency Hormonal Contraception With Ulipristal Acetate Versus Levonorgestrel for Minors in France. PMID- 27201568 TI - Cervical Assessment With Progesterone in the Prevention of Preterm Birth: A Strategy Based On Cost-Effectiveness. PMID- 27201569 TI - Cost-Effectiveness of Palivizumab Use in High Risk Children From Brazilian Health System Perspective. PMID- 27201570 TI - Cost-Effectiveness Analysis of the New Biomarkers for Diagnosis of Acute Kidney Injury in Children After Cardiac Surgery. PMID- 27201572 TI - Cost-Effectiveness Analysis of the Therapy of Endometriosis. PMID- 27201571 TI - Cost-Utility Analysis of Preventive Home Visits in Older Adults. PMID- 27201573 TI - Evaluation of the Economic Burden of Menopausal Women in the U. S. Medicaid Program. PMID- 27201574 TI - Cost-Utility Analysis Comparing Propranolol With Corticosteroids in the Treatment of Proliferating Infantile Hemangioma in Italy. PMID- 27201575 TI - Cost Effectiveness Analysis of A Vaccine To Prevent Herpes Zoster and Postherpetic Neuralgia in Italy. PMID- 27201576 TI - Cost-Utility Analysis of A Medication Review With Follow-Up for Older People With Polypharmacy in Community Pharmacies in Spain: Consigue Program. PMID- 27201577 TI - Retrospective Analysis of the Economic Burden of Long-Term Care Facility Residents Diagnosed With Alzheimer's Disease in the United States. PMID- 27201578 TI - Validation of the Adherence Barriers Questionnaire (Abq) - An Instrument for Identifying Potential Risk Factors Associated With Medication-Related Non Adherence. PMID- 27201579 TI - Stress Load Factors in the Scope of Students. PMID- 27201580 TI - Failure To Obtain the First Prescribed Refill (Early Medication Non-Persistence): A Meta-Analysis of Rates and Causes of Variation in Rates By Chronic Disease Class and Analytic Methods. PMID- 27201582 TI - Time-Trade-off Modelling of Health Utility Values for Menopausal Symptoms and Their Treatment. PMID- 27201581 TI - Patients' Acceptance of Their Medication: Results From a French Multi-Diseases Study With Patient Online Community Using the Acceptance By the Patients of Their Treatment (Accept(c)) Questionnaire. PMID- 27201583 TI - A Utility Algorithm forthe Pressure Ulcer Quality of Life - Utility Instrument (Puqol-Ui). PMID- 27201585 TI - Patient Perspective: Pro Compliance and Effective Reminder Strategies. PMID- 27201584 TI - Using the Analytic Hierarchy Process To Derive Health State Utilities From Ordinal Preference Data. PMID- 27201586 TI - Geographical Variations of Health Perception in the Us, Using Brfss Data 2012. PMID- 27201587 TI - Attitude Change Among 18-19 Years Old Boys After School-Drug Prevention Program. PMID- 27201589 TI - Patient-Reported Fall Related Health Care Services in Elderly Women. PMID- 27201588 TI - A Comparison of Value for Health States Worse Than Dead Between Japan and Uk. PMID- 27201591 TI - Differential Item Functioning and the Eq-5d: Evidence From the Uk Hospital Episode Statistics. PMID- 27201590 TI - Long-Term Grading of Health-Related Quality of Life of Care-Needed Elderly: A 2 Yr Follow-Up Study. PMID- 27201593 TI - Disutility Associated With Erectile Dysfunction in the Middle-Aged Or Older Males. PMID- 27201592 TI - Reference Eq-5d-3l and Eq-5d-5l Data From the Italian General Population. PMID- 27201594 TI - Antenatal Depression and Its Risk Factors Among Women in Chengdu of China Results From A Hospital Based Survey. PMID- 27201595 TI - Implementation of An Ambulatory Pharmacist-Managed Anticoagulation Clinic In Qatar: Development of A New Service and A Pilot On Patients' Satisfaction and Quality of Life. PMID- 27201596 TI - Family Preferences in the Volume Verse Outcome Debate: Implications for the Delivery of Complex Pediatric Care. PMID- 27201598 TI - Evaluating Prevalence of Self-Medication in Bahawalpur. PMID- 27201597 TI - A Systematic Review To Identify the Use of Preference Elicitation Methods in Health Care Decision Making. PMID- 27201599 TI - Patient Preferences: Pro Mixed Modes - Epro Versus Paper. PMID- 27201601 TI - Does Price Matter? The Impact of Cost Information On Patient Decision Making. PMID- 27201600 TI - Health Literacy and Self-Reported Health Status Using the Eq-5d-5l: An Exploratory Analysis. PMID- 27201602 TI - Assessment of Health States and Erectile Dysfunction-Associated Quality of Life Among Adult Males and Females With Male Partners in Germany, the United Kingdom and the United States. PMID- 27201603 TI - How Iranian People Think About Generic Substitution? PMID- 27201604 TI - Assessing the Translatability of the Term "Frustrated". PMID- 27201605 TI - Comparison of Equity Weights of Life Year Gains: A Discrete Choice Experiment for Japanese and Korean General Public. PMID- 27201606 TI - Mobile Phone Use in Patient Reported Outcomes- An Updated Literature Search. PMID- 27201607 TI - Regulatory Issues in Pro Advertising: A Review of the Ddmac/Opdp Letters From 1998 To 2013 To Identify Pro Claims Violations and Examine Their Evolution Over Time. PMID- 27201608 TI - Comparing the Equivalence of Eq-5d-5l Across Different Modes of Administration. PMID- 27201609 TI - Are Patient Reported Outcomes Relevant To Patients? Learnings From A Patient Advocate Survey. PMID- 27201610 TI - The Endometriosis Health Profile (Ehp) - A Case Study of Successful Epro Collaboration. PMID- 27201611 TI - The Use of Patient Reported Outcomes (Pros) By the Pharmaceutical Industry in Japan - A Brief Review of Pmda Data in Comparison With Fda and Ema-Approved Label Claims. PMID- 27201612 TI - Hospital Drg Costing and Health Services Use of Very Pre-Term Infants From the Proprems Neuro Study Across 10 Hospitals in Australia and New Zealand. PMID- 27201613 TI - Quality of Life in Pregnant Women Attending Anti-Natal Clinics in Rural and Urban Areas of Delta State. PMID- 27201614 TI - Health Related Quality of Life in Patients Receiving Home Enteral Nutrition in Spain Assessed By A Specific Questionnaire: Nutriqol(r). PMID- 27201615 TI - Theoretical and Practical Possibilities of the Measurement of Postoperative Pain in Obstetric Intensive Ward. PMID- 27201616 TI - Evaluating the Translatability of Physical Assessment Clinical Outcomes Assessment (Coa) Items. PMID- 27201617 TI - Fda Cdx Category Medication Use During Pregnancy in the United States. PMID- 27201618 TI - Implementation of A Collaborative Pharmacy Practice Model in Nursing Homes of A Swiss Canton: Drug Cost Monitoring Between 2009 and 2012. PMID- 27201619 TI - The Efficiency Evaluation of the Rule From Drug Market Regulation Chamber (Cmed) Proposed To Public Medicines Acquisitions. PMID- 27201620 TI - The Efficiency Evaluation of the Rule From Drug Market Regulation Chamber (Cmed) Proposed To Public Medicines Acquisitions in Antitrust Market Conditions. PMID- 27201621 TI - Evaluation of Patient and Financial Outcomes Associated With Advanced Infertility Treatment Options. PMID- 27201622 TI - Daily Dose and Costs Associated With Maintenance Therapy of Topical Testosterone Agents Among Hypogonadal Men. PMID- 27201624 TI - Aging Impact Over the National Health Cost in Extremadura Public Health Expenditure of Extremadura in the Period 2011-21. PMID- 27201623 TI - Impact of Assisted Reproductive Therapy (Art) On Infant Health and Health Care Cost Outcomes. PMID- 27201625 TI - Potentially Inappropriate Medicines and Potential Prescribing Omissions in Older People and Their Association With Health Care Utilization: A Retrospective Cohort Study. PMID- 27201626 TI - Predictions for Medical Subsidy Enrollment Among Young Children From High-Risk Families in Taipei. PMID- 27201628 TI - Kazakhstan Verse Uzbekistan: A Review of the Drug Provision Systems. PMID- 27201627 TI - Psychometric Properties of the 16-Item Sort form Version of the Menopause Cervantes Health-Related-Quality-of-Life Scale: the Cervantes-Sf. PMID- 27201629 TI - What Factors Are Associated With Vaccination Programme Success? PMID- 27201630 TI - Estimation of Serum Calcium Level in Peri and Postmenopausal Women: A Comparative Study. PMID- 27201631 TI - Patient-Reported Outcomes (Pro) in Go/No-Go Decision Making in Drug Development. PMID- 27201632 TI - Pain Incidence and Analgesic Consumption During Haemodialysis Sessions: Impact on Health-Related Quality Of Life. PMID- 27201633 TI - Patient Characteristics and Medication Treatment Patterns Among Men With Erectile Dysfunction (Ed), Lower Urinary Tract Symptoms Secondary To Benign Prostatic Hyperplasia (Bph-Luts), Or Co-Occurring Ed and Bph-Luts In the Uk Primary Care Setting. PMID- 27201634 TI - Clinical Utility of the Collect Scale To Assess Comorbidities In Patients With Chronic Lymphocytic Leukemia. PMID- 27201635 TI - Impact of Biologics Use on Depression and Anxiety Frequency and Health Care Resource Utilization In Psoriasis: An Analysis Using the Quebec Provincial Drug Reimbursement Program Database. PMID- 27201636 TI - A Real-World Characterization of Patients With "Moderate-To-Severe" Systemic Lupus Erythematosus. PMID- 27201637 TI - Effectiveness of Heavy-Light Chain Quantitative Test: A Systematic Review. PMID- 27201638 TI - Disappearance of B-Symptoms In Comorbid Patients Receiving First-Line Obinutuzumab (Ga101) -Chlorambucil (G-Clb) Or Rituximab-Chlorambucil (R-Clb) for Chronic Lymphocytic Leukemia (Cll). PMID- 27201639 TI - Comparison of Disease Status and Outcomes of Patients With Ankylosing Spondylitis (As) Receiving Adalimumab Or Etanercept Monotherapy In Europe. PMID- 27201640 TI - A Double-Blind Controlled Study of the Efficacy and Safety of Long-Acting Amfepramone Treatment In Mexican Obese Patients. PMID- 27201641 TI - Comparative Effectiveness Study of Enzymatic Replacement Therapies In the Treatment of Gaucherxs Disease On Adults. PMID- 27201642 TI - A Pilot Study of the Effectiveness of Treatment Patients With Hemophilia In Ukraine. PMID- 27201643 TI - The Oncology Pain Treatment Clinical Studies Quality Assessment. PMID- 27201645 TI - Prevalence and Treatment of Chronic Lymphocytic Leukaemia (Cll) In Germany: An Analysis of Sickness Funds. PMID- 27201644 TI - How To Improve Health Outcomes In the Treatment of Chronic Myeloid Leukemia. PMID- 27201646 TI - Pre-Symptomatic Genetic Testing In Familial Amyloid Polyneuropathy: The Reproductive Options. PMID- 27201647 TI - Trends In Prescription Opiate Use Among Patients With Commercial Or Government Sponsored Health Insurance In the Us From 2010-2013. PMID- 27201648 TI - Acute Myeloid Leukemia and Myelodisplasic Syndrome Treated With Intensive Chemotherapy In France Based On National Hospital Databases (Pmsi). PMID- 27201649 TI - Allogeneic Stem Cell Transplant With Graft Versus Host Disease In France In 2012 Based On National Hospital Databases (Pmsi). PMID- 27201650 TI - The Presence of Anxiety Among Elementary Schools Obese Children. PMID- 27201651 TI - Budget Impact Analysis of Drugs for Ultra-Rare Non-Oncological Diseases In Europe. PMID- 27201652 TI - Estimating the Costs of Drug Supply for Rare Diseases Patients In Russia. PMID- 27201654 TI - Budget Impact of Orphan Drugs In the Netherlands In The Period 2006-2012. PMID- 27201653 TI - Clinical and Cost-Effectiveness and Budget Impact of Routine Use of Bispectral Index Monitors In Theatres. PMID- 27201655 TI - Budget Impact Analysis of Introducing Biosimilar Infliximab for the Treatment of Auto Immune Disorders In Five European Countries. PMID- 27201656 TI - Budget Impact Analysis of Belimumab In the Treatment of Patients With Systemic Lupus Erythematosus In Russian Federation. PMID- 27201657 TI - Public Expenditure On Authorised Orphan Drugs In the Czech Republic Between 2008 and 2013. PMID- 27201658 TI - Qutenza(r) Estimated Costs Per Patient In Primary Versus Secondary Care. A Comparison Between Qutenza(r), Pregabalin and Lidocaine for the Treatment of Peripheral Neuropathic Pain. PMID- 27201659 TI - Economic Impact Linked To the Reduction of Exacerbations When A Treatment Regime With Inhaled Antibiotics Is Switched To Aztreonam Lysine In Patients With Cystic Fibrosis and Chronic Pulmonary Infection Caused By Pseudomonas Aeruginosa. PMID- 27201660 TI - Impact of Generic Substitution On the Prescribing of Meprobamate-Containing Combination Analgesics In South Africa. PMID- 27201661 TI - The Economic Burden of Treating Thalassemia In Greece. PMID- 27201662 TI - Economic Considerations On the Use of Mifamurtide In the Treatment of Osteosarcoma In Spain. PMID- 27201663 TI - Pill Burden, Health Care Resource Utilization and Costs Among Subpopulations of Immediate Release Hydrocodone Users. PMID- 27201664 TI - Opioid Prescribing and the Impact of Branded Generics. PMID- 27201665 TI - Cost Analysis In the Treatment of Patients With Systemic Lupus Erythematosus In Russian Federation. PMID- 27201666 TI - Rates of Diagnosed Opioid Abuse Or Dependence and Incremental Direct Health Care Costs Among Patients With Long-Term Use of Immediate Release Hydrocodone. PMID- 27201667 TI - Prevalence-Based Measurement of the Economic Burden of Rare Diseases: Case Review To Determine the Annual Cost of Acromegaly In France. PMID- 27201668 TI - Prevalence-Based Measurement of the Economic Burden of Rare Diseases: Case Review To Determine the Annual Cost of Acromegaly In Italy. PMID- 27201669 TI - Cost of Illness Analysis of Duchenne Muscular Dystrophy In Italy. PMID- 27201670 TI - Social Costs of Different Procedures In Bariatric Surgery In Patients With Obesity-Related Comorbidities. PMID- 27201671 TI - Costs of Absenteeism In Psoriatic and Enteropathic Arthropathies Based On Real Life Data From Poland's Social Insurance Institution Database In 2012. PMID- 27201672 TI - The Burden of Myelofibrosis In Greece. PMID- 27201673 TI - The Indirect Costs of Multiple Sclerosis Associated With Absenteeism In Poland. PMID- 27201674 TI - Romiplostim Cost Per Response In Itp Treatment In the Brazilian Health Care System. PMID- 27201675 TI - Direct and Indirect Costs Associated With Increasing Body Mass Index (Bmi) In the Eu5. PMID- 27201676 TI - Costs of Absenteeism In Ankylosing Spondylitis Based On Real-Life Data From Poland's Social Insurance Institution Database In 2012. PMID- 27201677 TI - The Economic Burden of Systemic Lupus Erythematosus: A Structured Literature Review. PMID- 27201678 TI - The Cost of Active Systemic Lupus Erythematosus in Greece Results From the Lycos Study. PMID- 27201679 TI - Cost-Effectiveness Analysis of Maintenance Treatment With Rituximab In Patients With Follicular Lymphoma Responding To First Line Induction Therapy In Portugal. PMID- 27201680 TI - An Evaluation of Medical Resource Utilisation In Patients With Autosomal Dominant Polycystic Kidney Disease In Europe. PMID- 27201681 TI - Cost Per Response Analysis for Thrombopoietin Receptor Agonists (Tpo-Ras), In the Treatment of Adult Chronic Immune Thrombocytopenia (Itp) In Mexico. PMID- 27201682 TI - Cross-Country Comparison of Medical Resource Utilisation In Patients With Autosomal Dominant Polycystic Kidney Disease In Europe. PMID- 27201683 TI - Cost-Effectiveness Analysis of Belimumab In the Treatment of Adult Systemic Lupus Erythematosus (Sle) Patients With Positive Biomarkers In Spain. PMID- 27201684 TI - Cost-Consequences Analysis of the Long-Term Prophylaxis In A Type 1 Von Willebrand Disease Patient With Recurrent Bleedings In Italy. PMID- 27201685 TI - Cost-Effectiveness Analysis of Amfepramone (Diethylpropion) for the Obesity Treatment In Mexico. PMID- 27201686 TI - The Cost-Effectiveness of Expanding the Nhs Newborn Bloodspot Screening Programme To Include Homocystinuria (Hcu), Maple Syrup Urine Disease (Msud), Glutaric Aciduria Type 1 (Ga1), Isovaleric Acidaemia (Iva), and Long-Chain Hydroxyacyl-Coa Dehydrogenase Deficiency (Lchadd). PMID- 27201687 TI - Cost-Effectiveness of the Lidocaine 5% Medicated Plaster Verse Pregabalin and Amitriptyline for the Treatment of Post-Herpetic Neuralgia In the Netherlands. PMID- 27201688 TI - Cost Effectiveness Analysis Evaluating Factor Viii As Primary Prophylaxis Treatment for Patients With Severe Haemophilia A In the Netherlands. PMID- 27201689 TI - Cost-Effectiveness of Capsaicin 8% Patch (Qutenza(tm)) Compared With Pregabalin for the Treatment of Patients With Peripheral Neuropathic Pain (Pnp) In Scotland. PMID- 27201690 TI - Belimumab for the Treatment of Systemic Lupus Erythematosus (Sle) In Greece: A Cost-Effectiveness and Cost-Utility Analysis. PMID- 27201691 TI - Cost-Effectiveness Analysis of Eltrombopag As Support Treatment In Chronic Hcv Infected Patients With Thrombocytopenia To Enable Interferon-Based Regimens. PMID- 27201692 TI - Comparative Pharmacoeconomic Analysis of the Application of Posaconazole, Fluconazole and Itraconazole With the Purpose of Primary Prevention of Invasive Fungal Infection In Patients With Neutropenia During Chemotherapy for Acute Myelogenous Leukemia Or Myelodysplastic Syndrome. PMID- 27201693 TI - Cost-Effectiveness Analysis of Oxycodone Lp An Opioid Analgesic for Patients With Moderate To Severe Pain Secondary To Cancer In Mexico. PMID- 27201694 TI - Cost-Effectiveness of Romiplostim for the Treatment of Chronic Immune Thrombocytopenia In Portugal. PMID- 27201695 TI - Cost-Minimization Analysis of Methadona Opioid Analgesic for Mexican Patients With Acute and Chronic Secondary Cancer As Rotation Option In Severe Pain. PMID- 27201696 TI - Cost Minimization Analysis of Activated Prothrombin Complex Concentrate (Apcc) Compared To Recombinant Factor Viia (Rfviia) for Hemophilia Patients With Inhibitors. PMID- 27201698 TI - Cost-Effectiveness Analysis of Celecoxib In the Treatment of Patients With Chronic Pain In Japan. PMID- 27201697 TI - Population-Based Cost-Efficiency Simulation of Partial Versus Complete Thromboprophylaxis In Hospitalized Patients In Saudi Arabia: Application of A British Model. PMID- 27201699 TI - Cost Effectiveness of Romiplostim for the Treatment of Immune Thrombocytopenia (Itp) Patients In the Czech Republic. PMID- 27201700 TI - Cost-Utility Analysis of Bosutinib for Previously Treated Chronic Myeloid Leukemia (Cml) In Portugal. PMID- 27201701 TI - Real-World Cost-Utility Evaluation of Multiple Myeloma Treatments In Stem Cell Transplanted Patients. PMID- 27201702 TI - Orphan Drug Pricing In France: Influence of Main Factors. PMID- 27201704 TI - Adherence To Anticoagulant Therapy In Children Hospitalized for Pulmonary Embolism and Deep Vein Thrombosis. PMID- 27201703 TI - Impact of Patient Programs On Adherence In Inflammation and Immunology: A Global Systematic Review and Meta-Analysis of Published Evidence. PMID- 27201705 TI - New Observer-Reported Outcomes To Measure Treatment Satisfaction, Compliance, Palatability, and Gi Symptoms for Patients Needing Iron-Chelation Therapy. PMID- 27201706 TI - Evaluation of Use of Belimumab In Clinical Practice Settings (Observe Study) In Spain: Health Resource Utilization and Labour Absenteeism. PMID- 27201707 TI - Is Obesity A Problem In Brazil? PMID- 27201708 TI - The Multicentric Castleman's Disease (Mcd) -Symptom Scale (Mcd-Ss): Development and Validation of A Patient-Reported Outcome (Pro) Measure for An Ultra-Orphan Disease. PMID- 27201709 TI - "I Don't Know How It Happened Or When Everything Changed. It's Like I Blinked and All of A Sudden, I Didn't Recognise My Own Body": Using Qualitative Insights To Develop A Conceptual Model To Understand the Lived Experience of Patients With Systemic Sclerosis. PMID- 27201710 TI - Prevalence of Neuropathic Pain and Its Disease Burden In Korea Patients With Lumbar Spine Surgery. PMID- 27201711 TI - Impact of Pulmonary Exacerbations On Eq-5d Measures In Patients With Cystic Fibrosis. PMID- 27201712 TI - Evaluating Relationship Between White Blood Cells and Platelets During Recovery Phase In Dengue Hemorrhagic Fever Cases In Punjab, Pakistan: A Retrospective Study. PMID- 27201713 TI - Psychometric Validation of the Newly Developed Phenylketonuria- Quality of Life (Pku-Qol) Questionnaires Assessing the Impact of Phenylketonuria and Its Treatment On Patients' Quality of Life. PMID- 27201714 TI - Pro Claims In Orphan Medicines Approved By the European Medicines Agency (Ema) for the Treatment of Lymphoproliferative Disorders. PMID- 27201716 TI - The Pain Assessment for Lower Back Symptoms (Pal-S): Refinement of A New Pro Instrument Through A Mixed Methods Approach. PMID- 27201715 TI - Impacts of Lower Back Pain: Refinement of the Pain Assessment for Lower Back Impacts Questionnaire (Pal-I) Using a Mixed Methods Approach. PMID- 27201717 TI - Patient-Reported Outcomes In Moderate To Severe Hemophilia Patients: Finding From A Cross-Sectionalstudy In Korea. PMID- 27201718 TI - A Systematic Literature Review of the Humanistic Burden of Multiple Myeloma. PMID- 27201720 TI - Preferences of Spanish Patients Over the Attributes of Biological Agents for the Treatment of Rheumatic Diseases Depending On the Administration Route. PMID- 27201719 TI - Preference for Rituximab Subcutaneous (Sc) and Intravenous (Iv) Among Patients With Cd20+ Non-Hodgkin's Lymphoma (Nhl) Completing the Rasq Measure In Randomized Phase Iii Studies Prefmab and Mabcute. PMID- 27201721 TI - Physicians' and Patients' Preferences Over the Attributes of Biological Agents Used In the Treatment of Rheumatic Diseases In Spain: A Conjoint Analysis. PMID- 27201722 TI - Quality of Life (Qol) With Psoriasis: Ethnography Study Evaluating the Impact of Psoriasis On Moderate To Severe Patients In Europe (Eu), From A Patient's Perspective. PMID- 27201723 TI - Health Related Quality of Life of Patients and Their Caregivers In Rare Diseases Results of the Burqol-Rd Project In Hungary. PMID- 27201724 TI - Is the Disease-Specific Lupusqol Sensitive To Changes of Disease Activity In Systemic Lupus Erythematosus Patients After Treatment of A Flare? PMID- 27201725 TI - The Quality of Life of Patients Treated With Robotic Versus Traditional Surgery Results From An Italian Observational Multicenter Study. PMID- 27201726 TI - Burden of Lupus Nephritis (Ln) Among Patients Managed In Routine Clinical Practices In Europe (Eu). PMID- 27201727 TI - Mcda Approach To Ranking Rare Diseases In Russia: Preliminary Results. PMID- 27201728 TI - Orphan Drug Policy: Approaches To Market Access In Multiple Countries. PMID- 27201729 TI - Characteristics of Patients With Systemic Lupus Erythematosus (Sle) Currently On Remission, With Active Disease But Not Experiencing Flare, and Those Experiencing Flares In Clinical Practices In Europe. PMID- 27201730 TI - Comparative Analysis of Hta Decisions, Price and Reimbursement Level of Orphan Drugs In France and Italy. PMID- 27201731 TI - Orphan Drug Approvals In Europe: Historical Review and Trends. PMID- 27201732 TI - Patterns and Trends In Opioid Use In Iran From 2007 To 2011. PMID- 27201733 TI - Health Technology Assessment, Price and Reimbursement Review for Orphan Drugs In Italy. PMID- 27201734 TI - Top 20 Orphan Drugs Availability, Pricing and Reimbursement In Slovakia: 2005 2012 Review. PMID- 27201736 TI - To What Extent Do Disease and Treatment Characteristics Influence Hta-Based Recommendations for A Sample of Orphan Drugs In Three Countries, and Could These Indicate Whether Orphan Drugs Have A "Special Status"? PMID- 27201735 TI - Why Are There Differences In Hta Recommendations Across Countries? A Systematic Comparison of Hta Decision Processes for A Sample of Orphan Drugs In Four Countries. PMID- 27201737 TI - Hta Studies On Orphan Drugs By Rebratsxmembers. PMID- 27201738 TI - Health Technology Assessment, Price and Reimbursement Review for Orphan Drugs In France. PMID- 27201739 TI - Database Analysis On Patients Using Immunobiological Drugs In A Brazilian Private Health Care Plan: A Real World Data Analysis. PMID- 27201740 TI - Health Care Utilisation and Selected Expenditures Associated With Neuroblastoma In England. PMID- 27201741 TI - Self Reported Health Care Resource Use and Indirect Economic Burden of Opioid Induced Constipation (Oic). PMID- 27201743 TI - Effect of Excluding Non-Patient Benefits As An Element On Acmg Newborn Screening (Nbs) Recommendations. PMID- 27201742 TI - Access To Orphan Drugs In Greece During Economic Crisis. PMID- 27201744 TI - Multi-Criteria Decision Analysis for Reimbursing Orphan Drugs: A Dutch Demonstration Study Using the Analytic Hierarchy Process Method. PMID- 27201745 TI - Variations In Treatment Patterns and Disease Severity Among Patients With Psoriasis Receiving Their First Biologic Therapy In Europe (Eu). PMID- 27201746 TI - Comparison of Treatment Patterns and Disease Severity Among Patients With Psoriatic Arthritis (Psa) Receiving Their First Biologic, Treated By Rheumatologists and Dermatologists In Europe (Eu). PMID- 27201747 TI - Behavior Therapy for Obesity Treatment Considering Approved Drug Therapy - An Update. PMID- 27201749 TI - Orphan and Rare Diseases - the Payer Perspective. PMID- 27201748 TI - Sources of Information and Pharmacists' Knowledge Regarding Rare Diseases and Orphan Drugs: Cross-Sectional Study In Serbia. PMID- 27201750 TI - Treatment Effect Heterogeneity in Clinical Trials: An Evaluation of 13 Large Clinical Trials Using Individual Patient Data. PMID- 27201751 TI - Hierarchical Network Meta-Analysis Incorporating Ordering Constraints on Increasing Doses of Interventions - Application to Overactive Bladder Syndrome. PMID- 27201752 TI - Predictors of Functional Disability in Patients With Chronic Lumbosacral Radicular Pain. PMID- 27201753 TI - Symtomatic Factors in Patients With Major Depressive Disorder (MDD): Results from an Observational Study. PMID- 27201755 TI - Assessing the Relationship Between Treatment Effect and Baseline Risk in Network Meta-Analsysis of Moderate to Severe Chornic Plaque Psoriasis Trials. PMID- 27201754 TI - Apoptosis and Oxidative Stress Induced By Exposure of Microwave Radiation In Rat Thymus: Modulatory Effect of Melatonin. PMID- 27201756 TI - Non-Treatment Specific Parameter Value Estimates: Relationship Between BMI and Utility. PMID- 27201757 TI - Comparison Of Iqwig and G-BA Benefit Ratings in Oncology. PMID- 27201758 TI - Survival Status in (Pharmaco) Epidemiological Studies can be Successfully Investigated Using Administrative Residential Registries. PMID- 27201759 TI - Recruiting Myelofibrosis Patients for Clinical and Health Outcome Studies Using Managed Physician Panels in 5 EU Countries. PMID- 27201760 TI - Can Gastric Cancer Patients be Successfully Recruited for Clinical Phase III/IV and Health Outcome Studies Using Managed Physician Panels? PMID- 27201761 TI - Riding the E-Publication Wave. PMID- 27201762 TI - Strengthening Evidence Base for Traditional Medicine in Asean, Quality of Reporting of Randomised Controlled Trials of Herbal Interventions in Asean Plus Six Countries: A Systematic Review. PMID- 27201763 TI - Individualised Growth Response Optimisation (IGRO): A Multi-Language Software Medical Device to Predict Growth Response in Children Treated With Growth Hormone (GH). PMID- 27201764 TI - Comparative Real World Effectiveness of Novel Agents Versus Conventional Therapies in Multiple Myeloma Patients in Sweden. PMID- 27201765 TI - Endpoints in Pain: the Suitability for Health Economic Evaluation of Endpoint Designs in Chronic Pain Studies. PMID- 27201766 TI - Predictive Modelling for Optimal Target Population and Real-World Study Design: An Example In Mother-To-Child Transmission of HIV. PMID- 27201767 TI - Predictive Modeling to Assess Predictors of Treatment Success and Failure Among Combination Statin Therapy Patients. PMID- 27201768 TI - Sharing of Information Across Studies to Inform Choice of Functional Form When Conducting Parametric Survival Analysis. PMID- 27201769 TI - Inverse Probability of Censoring Weighted Analysis to Adjust the Treatment Effect on Overall Survival for Subsequent Therapy: A Case Study in a Clinical Trial in Multiple Myeloma. PMID- 27201770 TI - Comparing the Use of Patient-Level Data to An Average Patient Profile Within a Type 2 Diabetes Simulation Model. PMID- 27201771 TI - Quantifying Nonlinear Effects in Stochastic Markov Simulation Using UKPDS 68 and Ukpds 82 Equations in Type 2 Diabetes Modeling Analysis With the IMS Core Diabetes Model (CDM). PMID- 27201772 TI - Validation of The Hospital Episode Statistics Outpatient Dataset in England. PMID- 27201773 TI - A Chart Abstraction Based Method to Classify Real World Patients With Pulmonary Arterial Hypertension Based on Who Functional Classification. PMID- 27201774 TI - Impact of Single Risk Factor Changes on Long Term Outcomes and Cost in a Type 2 Diabetes Modeling Study Contrasting Projections With UKPDS 68 Versus UKPDS 82 Risk Equations. PMID- 27201775 TI - The statistical analysis of delayed effects in survival outcomes for immunotherapies. Estimation of time-delay and application of weighted log rank. PMID- 27201776 TI - Quality Assessment of Controlled Trials Evaluating Chinese Herbal Medicine in Patients With Rheumatoid Arthritis: A Systematic Review. PMID- 27201777 TI - Identifying the Broader Value of Vaccines in Low and Middle Income Countries. PMID- 27201778 TI - Estimating Costs in A Cost-Effectiveness Analysis: Adherence to HTA Guidance. PMID- 27201779 TI - Should Changes in Drug Price Over Time be Considered in Cost-Effectiveness Analyses? PMID- 27201780 TI - Systematic Review and Critique of Health Economic Models on Relapsing-Remitting Multiple Sclerosis in the UK. PMID- 27201781 TI - Proposal for a Comprehensive Definition of Budget Impact Analysis. PMID- 27201782 TI - Can Using a Resource Use Log in an Economic Evaluation Alongside a Randomised Controlled Trial Reduce the Amount of Recall Bias? PMID- 27201783 TI - Episodes of Care and their Costs Based on ICPC-2 Classification: Three Month Follow-Up Study in Finland. PMID- 27201784 TI - Do the Us Panel Recommendations Hold for Europe? Investigating the Relation Between Quality of Life Versus Work-Status, Absenteeism and Presenteeism. PMID- 27201786 TI - A Systematic Review of Methods to Assess the Economic Impact of Air Pollution. PMID- 27201785 TI - Cost of Previously Treated Chronic Lymphocytic Leukemia (CLL) and Indolent Non Hodgkin's Lymphoma (INHL) in the United Kingdom (UK). PMID- 27201787 TI - Cost-Effectiveness Analysis of Ipilimumab in Previously Untreated Patients With Unresectable Malignant Melanoma in Scotland. PMID- 27201788 TI - IMTA Productivity Cost Questionnaire (IPCQ). PMID- 27201789 TI - A Review of The Utility Values Used in Published Cost-Effectiveness Analyses of Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Therapy in Patients With Diabetic Nephropathy. PMID- 27201791 TI - A Methodology for Estimating the Population of Advanced or Metastatic EGFR M+ Non Small Cell Lung Cancer Patients in the UK and Ireland. PMID- 27201790 TI - Are Care-Seekers Good Candidates for Subgroups Cost-Effectiveness Analyses? PMID- 27201792 TI - BCEA: A R Package to Perform Bayesian Cost-Effectiveness Analysis. PMID- 27201793 TI - Clusters of Health-States Valuations. PMID- 27201794 TI - Feasibility of the Headroom Analysis in Early Economic Evaluation of Innovative Diagnostic Technologies With no Immediate Treatment Implications. PMID- 27201795 TI - Modelling Dependence Between Disability Status and Health Service Costs of People With Rheumatoid Arthritis in Hungary. PMID- 27201796 TI - Pharmacy Cost Calculator for Hepatitis C Virus Patients in Turkey. PMID- 27201797 TI - A De-Novo Economic Model to Assess Clinical and Economic Consequences of Bronchiectasis. PMID- 27201798 TI - Different Strategies for Latent TB Assessment in Patients Undergoing Anti-TNF Treatment: an Economic Model. PMID- 27201799 TI - An Efficient Design for Cost-Effectiveness Studies of Personalized Medicine Strategies. PMID- 27201801 TI - Applying Multiple Criteria Decision Analysis in the Context of Health Technology Assessement: an Empirical Case Study. PMID- 27201800 TI - Methods for Health Economic Evaluations of Vaccines - Results from an International Expert-Workshop. PMID- 27201802 TI - Comparison of Generic, Condition-Specific and Mapped Health State Utility Values for Pediatric Asthma. PMID- 27201803 TI - Estimating Means from Medians: A Case Study With Treatments for Metastatic Colorectal Cancer (MCRC). PMID- 27201804 TI - Adopting an Evidence Synthesis Approach for Assessing Cost-Effectiveness of Screening Strategies for Prostate Cancer in Ireland. PMID- 27201805 TI - Preliminary Steps in the Development of an Algorithm for Identifying Relapsed CLL Patients in Secondary Data. PMID- 27201806 TI - Occurrence, Survival And Annual Cost of Colorectal-, Breast-, Prostate- and Lung Cancer in Hungary. PMID- 27201807 TI - Update of the Patient-Reported Outcome and Quality of Life Instruments Database (PROQOLID): Integration of The New COA Taxonomy - The Clinro Example. PMID- 27201808 TI - ECOA Licensing: Lessons Learned from the Copyright of COA Translations and Specificities of ECOAS. PMID- 27201809 TI - Mapping European Database Usage: An Analysis of Published Data Types. PMID- 27201810 TI - Using an Innovative Approach to Build a Prospective Diabetes Cohort Registry of Patients With Type 2 Diabetes in Germany: DIAREG. PMID- 27201811 TI - Impact of Influenza B in France. PMID- 27201812 TI - Insight In Health Care Databases in Asian Pacific Region. PMID- 27201813 TI - Evaluation of Dissemination of Brazilian Network for Health Technology Assessment (REBRATS). PMID- 27201814 TI - Analysis of the Expenses for the Introduction of Electric Medical Record System in the National Hospital Organization. PMID- 27201815 TI - A Dutch Administrative Database in Support of Economic Evaluations: A Feasibility Study. PMID- 27201816 TI - Common Pregnancy Symptoms Increase the Risk Of Cardiovascular Disease. PMID- 27201817 TI - Easy Come, Hardly Go: Epidemiological Methods to Evaluate the Effect of Ispor Board of Directors Membership on Publication Activity. PMID- 27201818 TI - Reimbursement Decisions in Oncology Drugs: An International Analysis. PMID- 27201819 TI - A Tutorial on Dimensionality Reduction in Large Claims Data Sets. PMID- 27201820 TI - INDIRECT COMPARISON OF THE EFFECTS OF ANTI-TNF BIOLOGICAL AGENTS IN PATIENTS WITH ANKYLOSING SPONDYLITIS BY MEANS OF A MIXED TREATMENT COMPARISON PERFORMED ON EFFICACY DATA FROM PUBLISHED RANDOMISED, CONTROLLED TRIALS. PMID- 27201821 TI - Increased Accuracy of Distribution Based Missing Value Imputation: An Alternative to Mean Inputation in Real World Environment Survey Research. PMID- 27201822 TI - Creating Patient Profile in Individual Simulations: A Comparison of Approaches. PMID- 27201823 TI - Application of A Model Of Decision Based on Fuzzy Logic to Pharmacoeconomics: Treatment of CROHN'S Disease With Antitnf in Out of Label Use. PMID- 27201824 TI - Multi-Criteria Decision Analysis (MCDA): Testing a Proposed Mcda Model for Orphan Drugs. PMID- 27201825 TI - Comparing Three Different Methods of Half-Cycle Correction. PMID- 27201826 TI - Use Of Model Averaging Techniques in Cost-Effectiveness Analysis in Oncology. PMID- 27201827 TI - Validation of the SPHR Diabetes Prevention Model. PMID- 27201828 TI - Advishe: a New Tool to Report Validation of Health-Economic Decision Models. PMID- 27201829 TI - Cost-Effectiveness Models for Chronic Obstructive Pulmonary Disease (COPD): Cross Model Comparison of Hypothetical Treatment Scenarios. PMID- 27201830 TI - Comparison of Methods to Estimate Health State Utilities in Metastatic Breast Cancer (MBC). PMID- 27201831 TI - Approaches Used to Model the Relationship Between Progression-Free Survival (PFS) / Time-To-Progression (TTP) And Overall Survival (OS) Within Health Economic Models of Cancer Therapies. PMID- 27201832 TI - Health Economic Models in Alzheimer's Disease: A Critical Assessment. PMID- 27201833 TI - Modelling Survival in the Presence of Different Mechanisms of Action: Ipilimumab and Vemurafenib in Advanced Melanoma. PMID- 27201834 TI - Are Cycles Needed in Markov Models? - The Continuous Model as a Simpler Approach. PMID- 27201836 TI - All-Cause Mortality Validation of the Core Diabetes Model Against Predictions of the Charlson Comorbidity Index. PMID- 27201835 TI - Deterministic Versus Stochastic Prediction of Risk for Cardiovascular Events. PMID- 27201837 TI - Estimating the Lifetime Health Outcomes of Type 2 Diabetes Mellitus (T2dm) Patients Inadequately Controlled on Metformin Plus Sulphonylurea Receiving Either Canagliflozin or Sitagliptin Using the UKPDS Outcomes Model V1.3. PMID- 27201838 TI - A Comparison of Modelling Techniques: Patient Simulation Verse Markov Modelling in Ophthalmology. PMID- 27201839 TI - A DE-NOVO Model to Predict Outcomes of a New Hypothetical Intervention to Reduce CV Risk in Post Mi Patients. PMID- 27201840 TI - Validation of A Global Economic Model to Evaluate The Cost-Effectiveness Of Targeted Treatments Using Companion Diagnostics In Advanced/Metastatic Cancer Treatment Using Kras Testing For Cetuximab Therapy In Metastatic Colorectal Cancer. PMID- 27201841 TI - Clinical Trial Simulation Considering Quality Of Life Outcomes. PMID- 27201842 TI - Systematic Overview On Value-Of Information Analyses In Cancer Research. PMID- 27201843 TI - The Oncotyrol Prostate Cancer Outcome and Policy Model - How Latent Prevalence Affects the Benefit-Harm Balance of Screening. PMID- 27201844 TI - A Systematic Search and Methodological Review of Economic Models of Analgesics for Chronic Pain. PMID- 27201845 TI - MIGRATION OF HEALTH ECONOMICS MODELS TO WEB AND MOBILE ENVIRONMENTS. WHY SHOULD MODELS GO WEB? PMID- 27201846 TI - Validating A Model To Predict Disease Progression Outcomes In Patients With COPD. PMID- 27201848 TI - Cost-Effectiveness Analysis Of An Antimicrobial Transparent Dressing For Protecting Central Vascular Accesses In Critically Ill Patients Versus Standard Transparent Dressings In France: A Comparison Of Two Modeling Approaches: Decision-Tree Versus Non-Homogeneous Markov Model. PMID- 27201847 TI - Systematic Review Of Mathematical Models Predicting Relative Effectiveness. PMID- 27201849 TI - HEALTH ECONOMIC EVALUATION OF DIAGNOSTIC AND PROGNOSTIC PREDICTION MODELS. A SYSTEMATIC REVIEW. PMID- 27201851 TI - Development Of An Influenza Outbreak Forecasting Model Using Time Series Analysis Methods. PMID- 27201850 TI - Application Of A Model Of Decision Based On Fuzzy Logic To Pharmacoeconomics: Ranibizumab Verse Aflibercert In AMD. PMID- 27201852 TI - A Web Based Optimisation Model For A Portfolio Of Preventative Interventions Utilizing Multi Criteria Decision Analyses (Mcda) Framework. PMID- 27201853 TI - Calibration And Statistical Modeling To Inform A Micro-Simulation Model For Early HTA. PMID- 27201854 TI - How Does Uncertainty Around Costs And Effects Relate To Uncertainty Around Cost Effectiveness? PMID- 27201855 TI - Development Of A Global Economic Model To Evaluate The Cost-Effectiveness Of Targeted Treatments Using Companion Diagnostics In Advanced/Metastatic Cancer Treatment. PMID- 27201856 TI - Visualizing Methods For Discrete-Event-Simulations Using The Example Of A Breast Cancer Decision-Analytic Model. PMID- 27201857 TI - Assessing The Relationship Between Individual Attributes Identified In Review Of Multi-Criteria Decision Analysis (MCDA) Of Rare Diseases And Annual Treatment Costs In Rare Endocrine Disorders. PMID- 27201858 TI - Development Of A Model To Assess The Cost-Effectiveness Of Therapies For Patients With Type 2 Diabetes Mellitus (T2DM) Following A Reference Model Framework. PMID- 27201860 TI - Methodological Evaluation Of The Impact Of Survival Costs In Oncology Modelling. PMID- 27201859 TI - Microsimulation Model For The Assessment Of Personalized Cancer Care: The Mapcca Model Framework. PMID- 27201861 TI - Use Of External Data To Guide Long-Term Survival Extrapolations Of Trial Data For Chronic Lymphocytic Leukemia. PMID- 27201862 TI - Modelling Evolving Cancer Risk During Epidemiological Transition Using Economic Data. PMID- 27201863 TI - Modeling Disease Progression In Alzheimer's Dementia To Inform HTA (CEA). PMID- 27201864 TI - Impact Of International And Therapeutic Referencing On Prices And Launch Optimization. PMID- 27201865 TI - Dose-Response Network Meta-Analysis To Address Dose Heterogeneity In A Cost Effectiveness Analysis In Acute Migraine. PMID- 27201866 TI - Forecasting Cancer Incidence Using Gross Domestic Product. PMID- 27201867 TI - Development Of A Model To Predict Disease Progression In Autosomal Dominant Polycystic Kidney Disease (ADPKD). PMID- 27201868 TI - Estimating Crossover Bias In A Randomized Clinical Trial Of Ovarian Cancer Treatment. PMID- 27201870 TI - Stratified Cost-Effectiveness Analysis To Guide Genetic Screening For Cancer Risk. PMID- 27201869 TI - Cost-Effectiveness Modeling Of Antimicrobial Dressings For Preventing Catheter Related Bloodstream Infection: Homogeneous Verse Non-Homogeneous Markov Approaches. PMID- 27201871 TI - The Impact Of The New Drug Co-Payment Scheme On Economic Evaluations In Spain. PMID- 27201872 TI - Modelling Long-Term Changes In Opioid Induced Constipation (OIC). PMID- 27201873 TI - Discrete Event Simulation For The Cost-Effectiveness Evaluation Of Pet-Ct Scans In The Diagnosis Of Conn's Disease In Hypertensive Patients. PMID- 27201874 TI - Patient Preferences And Hiv Drugs: What About Uncertainty? PMID- 27201875 TI - Companion Diagnostics-Targeted Therapies Pairings Model-Based Economic Evaluation: Reflection On A General Modeling Framework And Key Methodological Points. PMID- 27201876 TI - MODELLING HEALTH-RELATED QUALITY OF LIFE (HRQOL) LONGITUDINALLY. A BAYESIAN MIXED BETA REGRESSION APPROACH. PMID- 27201877 TI - Effect Of Sample Size And Data Maturity On Parametric Survival Modeling Projections In Advanced Cancer. PMID- 27201878 TI - Understanding Real Life Treatment Patterns Among Patients With Hypertension: A Markov Model. PMID- 27201879 TI - The Proportional Odds Model Is More Efficient Than The Multinomial Logistic Model For Network Meta-Analyses Of Ordered Outcomes. PMID- 27201880 TI - Predictive Modelling: Predicting Hospitalisation And Estimating The Cost And Risk To The Third Party Funder. PMID- 27201881 TI - Joint Modelling Of The Change In Tumor Size And Overall Survival; A Parametric Model Considering Patient Heterogeneity Not Observed At Baseline. PMID- 27201882 TI - Evaluating The Effect Of Immunotherapy In Advanced Non-Small- Cell Lung Cancer Patients Using Two Components Mixture Model. PMID- 27201884 TI - Mapping Fact-P To EQ-5D In Metastatic Castration-Resistant Prostate Cancer (MCRPC): Performance Of A Previously Developed Algorithm When Applied On A Sample With A Different Disease Stage. PMID- 27201883 TI - How Do Individuals Complete The Choice Tasks In A Discrete Choice Experiment? PMID- 27201886 TI - Assessment Of The Huntington Clinical Self-Reported Instrument (H-CSRI) Cross Cultural Validity. PMID- 27201885 TI - Severity And Functional Disability Of Patients With Occupational Contact Dermatitis: Validation Of The German Version Of The Occupational Contact Dermatitis Disease Severity Index (ODDI). PMID- 27201887 TI - Assessment Of The Huntington Quality Of Life Instrument (H-QOL-I) Cross-Cultural Validity. PMID- 27201888 TI - Psychometric Evaluation Of The Patient's Knee Implant Performance (PKIP) Questionnaire For The Assessment Of Primary Total Knee Arthroplasty. PMID- 27201889 TI - Validity And Responsiveness Of The Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire (BRAF-MDQ) In A Randomized Controlled Clinical Trial. PMID- 27201890 TI - THE DEVELOPMENT AND PRELIMINARY VALIDATION OF THE MANCHESTER SLEEP SYMPTOMS INDEX (MSSI) FOR PEOPLE WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD). PMID- 27201891 TI - DISCRETE-CHOICE EXPERIMENT VERSE RATING SCALE EXERCISE TO EVALUATE THE RELATIVE IMPORTANCE OF ATTRIBUTES: A STUDY OF THE MAASTRICHT ISPOR STUDENT CHAPTER. PMID- 27201892 TI - The Measurement Of Utilities In Asthma Patients: A Preliminary Study. PMID- 27201893 TI - RASCH FIRST? FACTOR FIRST? PMID- 27201894 TI - Patient Reported Utilities In First-Line Advanced Or Metastatic Melanoma: Analysis Of Trial CA184-024. PMID- 27201895 TI - Cdad-DaysymsTM: A New Patient-Reported Outcome Tool For Clostridium Difficile Associated Diarrhoea. PMID- 27201896 TI - Predicting Suicidal Behavior In Veterans And Active Military Personnel: Possibilities For Electronic Deployment To Discover A Predictive Assessment. PMID- 27201897 TI - The Influence Of Gene Expression Profiling (GEP) On Decisional Conflict In Chemotherapy Treatment Decision-Making For Early-Stage Breast Cancer (BRCA). PMID- 27201898 TI - Development And Content Validity Testing Of A Treatment Acceptance Measure For Use In Hypercholesterolemia Patients Receiving Treatment Via Subcutaneous Injection. PMID- 27201900 TI - An Evaluation of the Performance of Eq-5d: A Review of Reviews of Psychometric Properties. PMID- 27201899 TI - Health-Related Quality of Life in Italian Patients With Moderate and Severe Crohn's Disease: Interim Results from the Sole Study. PMID- 27201901 TI - Validity of the Eq-5d-5l in Stroke Patients. PMID- 27201902 TI - Physicians' Preferences for Bone Metastases Treatments in Turkey. PMID- 27201903 TI - Re-Validation of the Self-Injection Assessment Questionnaire(c) (Siaqv2.0(c)) in Rheumatoid Arthritis Patients on Certolizumab Pegol Treatment. PMID- 27201904 TI - Current Sample Size Practices in the Psychometric Evaluation of Patient-Reported Outcomes for Use in Clinical Trials. PMID- 27201905 TI - A Reliability Generalisation of the Eortc Qlq-Br23. PMID- 27201906 TI - Improving Performance in Diabetes Care: Benefits of Information Technology Enabled Diabetes Management. PMID- 27201907 TI - Re Introduction of the Ranking Task in Eq-5d Valuation. Improved Data Quality and Reduced Level of Inconsistencies? PMID- 27201908 TI - Are "Lively" and "Full of Pep" Similar Or Different Concepts? Challenges in Translating These Terms in Seven Languages. PMID- 27201909 TI - Efficacy of Virtual Reality Exposure Therapy in the Management of Symptoms Associated With Post Traumatic Stress Disorder. PMID- 27201911 TI - The Development and Preliminary Validation of the Manchester Early Morning Symptoms Index (Memsi) for People With Chronic Obstructive Pulmonary Disease (Copd). PMID- 27201912 TI - What Is the Appropriate Comparator Health State To Use in Time Trade-off Studies? PMID- 27201910 TI - An Electronic Version of the Pdq-39: Acceptability To Respondents and Assessment of Alternative Response formats. PMID- 27201914 TI - Quality of Life Elements in Schizophrenia for Patients and Carers offer Challenges To and Opportunities for Intervention. PMID- 27201913 TI - Assessing the Methodological Value of Digital Real-Time Collection of Qualitative Content in Supporting In-Depth Qualitative Interviews Exploring the Symptoms and Impacts of Gout on Health-Related Quality of Life. PMID- 27201915 TI - An Analysis of the Health Technology Assessment Recommendation and Guidance on Use of Eq-5d-5l in Cost-Effectiveness Modeling. PMID- 27201917 TI - The Selection of Appropriate Health State Utility Values (Hsuvs) for Health Technology Assessment (Hta): Lessons To Be Learnt. PMID- 27201916 TI - From Clinically Relevant Outcome Measures To Quality of Life in Epilepsy. PMID- 27201918 TI - Translation and Linguistic Validation of the Electronic Colombia Suicide Severity Rating Scale in Asia-Pac. PMID- 27201919 TI - Health Related Quality of Life in Cancer Patients: Evaluation With A Self Administered Ipad Application. PMID- 27201920 TI - Comparability of Interview and Self-Administration of the Functional Assessment of Chronic Illness Therapy-Tuberculosis (Facit-Tb) Instrument in Iraqi Pulmonary Tuberculosis Patients. PMID- 27201921 TI - Quality of Life in Patients Undergoing Hemodialysis: A Vision of the Influence of Time. PMID- 27201922 TI - Patient Driven Questionnaire Development, Item Feedback from Users of A Patient Network. PMID- 27201923 TI - Impact of Osteoporotic Fractures on Quality of Life - Design of A Mapping Study of Qualiost To Eq-5d. PMID- 27201924 TI - Methods Used To Measure Patient Preferences In Psoriasis Treatments - An Overview With Regards To The German Iqwig And G-Ba. PMID- 27201925 TI - The Importance of Migration Assessments: Ecoa Translations and Linguistic Validation. PMID- 27201926 TI - Modification of Patient Reported Outcomes Measures of Compliance, Gastrointestinal Symptoms, Palatability and Treatment Satisfaction for Patients Needing Iron Chelation therapy. PMID- 27201927 TI - Development of the Behavior Rating Inventory of Executive Function - Preschool Version (Brief-P) in 10 Languages. PMID- 27201928 TI - Challenges In Recruiting Patients For The Linguistic Validation Of Pro Instruments Developed For Rare Diseases: A Case Study With Alagille Syndrome. PMID- 27201929 TI - Responsiveness and Minimal Clinically Important Difference of A Specific Health Related Quality of Life (Hrqol) Questionnaire for Home Enteral Nutrition (Hen) Patients: Nutriqol(r) Questionnaire. PMID- 27201930 TI - Methods To Elicit Patient Preferences: A Case Study In Metastatic Breast Cancer. PMID- 27201931 TI - Measuring Change in Quality of Life: Can We Distinguish Recall Bias and Scale Recalibration? PMID- 27201932 TI - Review of Patient-Reported Outcomes in Diabetic Macular Edema. PMID- 27201933 TI - Evaluation of Methods for the Inclusion of Real World Evidence in Network Meta Analysis - A Case Study in Multiple Sclerosis. PMID- 27201934 TI - Integrating Health Psychometrics With Health Economics: Can the 'Mapping' Toolbox Be Extended Using Ordinal Structural Equation Models? PMID- 27201935 TI - Frequentist Approach for Detecting Heterogeneity in Meta-Analysis Pair-Wise Comparisons: Enhanced Q-Test Use By Using I2 and H2 Statistics. PMID- 27201936 TI - Real-World Verse Randomised Controlled Trial Data: A Case Study On The Cost Effectiveness Of Laparoscopic Surgery For Chronic Reflux. PMID- 27201937 TI - The Use and Acceptance of Novel Statistical Analyses To Support Technology Submissions To Hta Authorities. PMID- 27201938 TI - Meta-Analysis in Open Bugs: How To Assess the Convergence of Mcmc Chain? PMID- 27201939 TI - Adjusting for Treatment Crossover in A Trametinib Metastatic Melanoma Rct: Identifying the Appropriate Method. PMID- 27201940 TI - Assessing Balance in Baseline Characteristics Using Different Propensity Adjusted Methods for Bipolar I Mixed Disorder Patients Initiating Asenapine Versus Other Oral Atypical Antipsychotics. PMID- 27201941 TI - Graphical Interactive Meta-Analysis Module for Facilitating Evidence-Based Decision Making in Health Care. PMID- 27201942 TI - Task-Based Versus Case-Based Analysis of Time Outcomes in Multi-Country Time and Motion (T&M) Studies: Methodological Considerations and Application. PMID- 27201943 TI - Knowledge on Medication Taking Behaviour, Balanced Diet and Physical Activity - A Survey Among the Adolescents. PMID- 27201944 TI - Development of A Web-Based Tool To Elicit the Opinion of Regionally Dispersed Health Care Professionals Responsible for Medical Device Vigilance. PMID- 27201945 TI - Analysis of Volume and Structure of Oral Antidiabetic Drugs Consumption in Ukraine. PMID- 27201946 TI - The Lumley-Method, A Recommended Network Meta-Analysis for Indirect Comparisons, Summarized for Practitioners. PMID- 27201947 TI - Multi-Level Network Meta-Analysis To Account for Dose-Response and Class Effects. PMID- 27201948 TI - An Evaluation and Comparison of Methods Used in Survival Analysis To Fit Distributional Curves To Kaplan-Meier Data. PMID- 27201949 TI - Proposed Checklist for Non-Statisticians To Assess the Quality of A Network Meta Analysis in the Context of A Nice Submission. PMID- 27201950 TI - Methodological Assessment of Matching-Adjusted Indirect Comparisons: Case Study Application To Attention Deficit/Hyperactivity Disorder (Adhd). PMID- 27201951 TI - Systematic Review and Critical Appraisal of the Statistical Methods Used in Published Studies To Indirectly Compare Novel Anticoagulants (Noacs) With Warfarin for the Prevention of Stroke in Patients With Atrial Fibrillation (Af). PMID- 27201952 TI - Uncertainty and Probabilistic Methods in Multi-Criteria Decision Analysis. PMID- 27201953 TI - Modeling the Effect of Combining Alogliptin With Dual therapy in Type 2 Diabetes. PMID- 27201954 TI - Simulating Individual Patient Level Data To Address Treatment Switching When Only Summary Data Are Available. PMID- 27201955 TI - Identifying Psoriasis and Psoriatic Arthritis Patients in Retrospective Databases When Diagnosis Code Is Not Available: A Validation Study Comparing Medication/Prescriber Visit Based Algorithms To Diagnosis Codes. PMID- 27201956 TI - Modelling Longitudinal Trajectories of Patient-Reported Outcomes To Evaluate Treatment Effect. PMID- 27201957 TI - Methodology For Selecting Expert Groups For The Purpose Of Decision-Making Tasks. PMID- 27201958 TI - The Randomized Blind Start Trial: Evaluation of A New Study Design for Assessing Clinical Outcomes in Rare and Heterogeneous Patient Populations. PMID- 27201959 TI - The Quality of Search Methodology and Search Reporting in Published Systematic Reviews of Economic Evaluations: Search Sources. PMID- 27201960 TI - Assessing the Effectiveness of Counter Matching for Improving the Efficiency of the Nested Case-Control Design in Observational Studies. PMID- 27201961 TI - Assessment of the Methodological Quality of Randomized Controlled Trials Published in "Russian Allergology Journal" in 2009-2013. PMID- 27201962 TI - Simulation of An Additional Go/No-Go Efficacy Interim Analysis in A Head-To-Head Rct. PMID- 27201963 TI - Immature Survival Data From Early Trial Termination - Theory and Hta Practice. PMID- 27201964 TI - Evidence Resulting From Chart Review Methodology Applied To Named Patient Programme Participation And Compassionate Medication Use: Peri-Approval Approximation Of Post-Market Practice Patterns And Costs. PMID- 27201965 TI - Negative Reimbursement Consequences From Trial Design Choices. PMID- 27201966 TI - The Management of Irritable Bowel Syndrome (Ibs) in England: A Real World Study in Primary Care Clinical Practice. PMID- 27201967 TI - The Effect of A Likely Overemphasis on Ficiency-Related Test Attributes on Acmg Recommendations and Access To Newborn Screening (Nbs). PMID- 27201968 TI - Workflow Mapping for Paediatric Vaccination Process in the United Kingdom (Uk): A Precursor of A Time and Motion (T&M) Study. PMID- 27201969 TI - (Cost-) Effectiveness of A Multi-Component Intervention for Adults With Epilepsy: Study Protocol of A Dutch Randomized Controlled Trial. PMID- 27201970 TI - Comparative Effectiveness Research of Medical Devices - New Methods Needed? PMID- 27201971 TI - Implementation of International Chart Review Studies: An Assessment of Ethics and Regulatory Considerations. PMID- 27201972 TI - Cost Per Patient in Non Interventional Studies and Added Value of Direct To Patient Contact Service. PMID- 27201973 TI - Retrospective Chart Review Studies: Strategies To Ensure Robust Data Quality. PMID- 27201974 TI - Research Prioritization In An Mcda Context: Existing Methods - New Results. PMID- 27201975 TI - A Statistical Modeling Framework To Characterize the Impact of Progression on Survival in Oncology. PMID- 27201976 TI - Towards Integration of Research Evidence on Patient Preferences in Coverage Decisions and Clinical Practice Guidelines: A Proposal for A Taxonomy of Preference-Related Terms. PMID- 27201977 TI - When It May Not Be Necessary To Model Overall Survival for Economic Evaluations of Anti-Cancer Drugs. PMID- 27201978 TI - A Framework for the Economic Evaluation of Sequential Therapies for Chronic Conditions. PMID- 27201979 TI - Feasibility of Conducting Retrospective Studies Using Hashtags and Social Media Data From Facebook and Twitter. PMID- 27201980 TI - Novel Indirect Comparison Methodology for Estimating Time-Dependent Response To Antimuscarinics for the Treatment of Oab. PMID- 27201982 TI - Effective Prioritisation of National Health Technology Assessments. PMID- 27201981 TI - Bayesian Models for Cost-Effectiveness Analysis in the Presence of Structural Zero Costs. PMID- 27201983 TI - Goal Attainment Scaling - A Useful Individualized Clinical Outcome Measure. PMID- 27201984 TI - Avoiding and Identifying Errors and Other Threats To the Credibility of Health Economic Models. PMID- 27201985 TI - Impacts of Epro Data Collection Mode Selection on Patient Inclusion. PMID- 27201986 TI - Clinical Outcome Assessment (Coa) Instrument Scoring: the Validity and Precision of Unweighted Summary Scores Verse Irt Weighted Scores, and the Added Value of Irt Standard Errors. PMID- 27201987 TI - Evaluation of Estimators of Treatment Effect in Observational Studies. PMID- 27201988 TI - Assessing Heterogeneity of Treatment Effect Using Real World Data. PMID- 27201989 TI - Challenges In Meeting Evidence Needs Of Payer, Physician, Patient And Industry Stakeholders For Novel Therapeutics. PMID- 27201990 TI - Health Technology Assessments for Personalised Medicines: Are Current Methodologies Suitable for the Assessment of Personalised Therapies? PMID- 27201992 TI - Multiple Decision Criteria for Assessing An Incremental Cost-Effectiveness Ratio of Expensive Health Technologies. PMID- 27201991 TI - Efficacy, Effectiveness and the "Efficacy-To-Effectiveness Gap": Review of the Current State of Play and Perspectives. First Results From the Imi Getreal Consortium. PMID- 27201993 TI - Health Technology Assessment and Environmental Costs: Time for Health Care To Catch Up? PMID- 27201994 TI - Non-Interventional Research Ethical Requirements in England and France: Shared Experience From A Binational Research Project. PMID- 27201995 TI - An Epidemiologic Modeling Application To Pharmacoeconomics for Improved Health Care Planning. PMID- 27201996 TI - Getting To Reimbursement Faster: Combining Randomised, Pragmatic, and Observational Clinical Trial Data. PMID- 27201997 TI - Propensity Score Matching and Subclassification With Multi-Level Treatments. PMID- 27201998 TI - Real World Studies, Challenges, Needs and Trends from the Industry. PMID- 27201999 TI - Pathways of Implementation of Multi-Criteria Decision Analysis Into Orphan Drug Approval Procedure for Drug Supply Programs in Russian Federation. PMID- 27202000 TI - Publication Manual of Budget Impact Analysis (Bia) by the Department of Science and Technology of the Ministry of Health (Decit). PMID- 27202002 TI - Effectiveness of Montelukast on Asthma Control in Infants: A Claims Data Study. PMID- 27202001 TI - Prospective Study on Cost-Effectiveness of Nurse Interviw Introducing Retesting With in Vitro Diagnostics (IVD) To Parents of Children With Suspected Food Allergy in Finland. PMID- 27202003 TI - Clinical Trial-Based Cost-Effectiveness Analysis of Indacaterol (ONBREZ(r) 150 MCG) Versus Tiotropium (SPIRIVA(r)) in the Treatment of Chronic Obstructive Pulmonary Disease (COPD) IN TURKEY. PMID- 27202004 TI - A Network Meta-Analysis Comparing the Efficacy And Safety of Ceftobiprole and Selected Comparators in the Treatment of Hospital-Acquired Pneumonia. PMID- 27202005 TI - Comparative Efficacy of Umeclidinium Bromide Versus Other Long-Acting Anticholinergic Monotherapies as Treatments for Copd Patients. PMID- 27202006 TI - A Database Study to Investigate the Incidence of Anaphylaxis and the Prescription Rate of Self-Injection Epinephrine in Japan. PMID- 27202007 TI - Systematic Review of Observational Studies and Rcts of Omalizumab in Severe Persistent Allergic Asthma and Meta-Analysis Feasibility Assessment. PMID- 27202008 TI - Impact of Omalizumab on Poor Asthma Control Events and Medication Utilisation in Patients With Moderate or Severe Persistent Asthma. PMID- 27202009 TI - Indirect Comparison of Exacerbation Frequency Between Aclidinium and Tiotropium in Patients With Chronic Obstructive Pulmonary Disease. PMID- 27202010 TI - Treatment Plan Comparison: An Observational Study of the Marche Region. PMID- 27202011 TI - Current Annual Cost Calculation is the Best Predictor of Mortality at Three Years in COPD. PMID- 27202012 TI - The Prevalence of Tobacco Smoking in Patients With Diabetes in Hospital Pulau Pinang, Malaysia. PMID- 27202014 TI - Estimating Smoking Cessation Rates and Smoking Prevalences Using Public Data and a Published Dynamic Model. PMID- 27202013 TI - Epidemiology and Severity of Chronic Obstructive Pulmonary Disease (COPD) in the United Kingdom (UK). PMID- 27202015 TI - Incidence and Prevalence of COPD By Gold 2013 Classification in the Netherlands. PMID- 27202016 TI - Patients With COPD who Initiate Roflumilast in Sweden. PMID- 27202017 TI - Estimation of Increased Costs in Switching from Tiotropium to Other Lama Therapy During Maintenance Treatment of COPD in the UK. PMID- 27202018 TI - The Economic Impact of Therapy Optimization in Chronic Obstructive Pulmonary Disease in Portugal. PMID- 27202019 TI - The Budget Impact of Duoresp(r) Spiromax(r) (Budesonide + Formoterol Fumarate Dihydrate) Compared With Symbicort(r) Turbohaler(r) for the Management of Asthma and Chronic Obstructive Pulmonary Disease in the United Kingdom: Impact on Health Care Costs and Inhalation Technique. PMID- 27202020 TI - Budgetary Implications of Introducing Fluticasone Furoate/Vilanterol for Asthma in the UK. PMID- 27202021 TI - Budgetary Implications of Introducing Fluticasone Furoate/Vilanterol for COPD in the UK. PMID- 27202022 TI - Economic Burden of Hospitalized Pneumonia from a Private Health Care System Perspective in Brazil. PMID- 27202023 TI - Cost-Minimization and Budget-Impact Analysis of Fixed-Dose Combination Inhalers in Treatment of Copd in Slovenia. PMID- 27202024 TI - Cost-Minimization and Budget-Impact Analysis of Fixed-Dose ICS/LABA Combination Inhalers in the Treatment of Asthma in Slovenia. PMID- 27202025 TI - Benefit of Positive Airway Pressure (PAP) Therapy in Sleep Apnoea (SA) Patients With Chronic Obstructive Pulmonary Disease (COPD) in Germany: A Retrospective Comparative Cohort Analysis Based on a Statutory Health Insurance Database. PMID- 27202026 TI - An Analysis of Us Medicare Beneficiaries: Burden of Direct Medical Costs in Patients With Idiopathic Pulmonary Fibrosis. PMID- 27202027 TI - Examination of the Burden of Illness of U. S. Medicare Patients Diagnosed with Chronic Obstructive Pulmonary Disease. PMID- 27202028 TI - The Cost Burden of Community-Acquired Pneumonia in Russia in Adults of 50 and Older: A Regional Study and National Estimates. PMID- 27202029 TI - The Medical Costs of Chronic Obstructive Pulmonary Disease in South Korea. PMID- 27202030 TI - The Direct Cost of Asthma in Turkey. PMID- 27202031 TI - Economic Burden in Direct Costs of Chronic Obstructive Pulmonary Disease (COPD) in Russia. PMID- 27202032 TI - Estimation of the Cost of Childhood Asthma in Turkey. PMID- 27202033 TI - Cost of a Pulmonary Arterial Hypertension-Related Hospitalization in Belgium. PMID- 27202034 TI - The Cost Study of Health Services in Mongolia. PMID- 27202035 TI - Resource Use and Health Care Costs of Chronic Obstructive Pulmonary Disease in Slovakia. PMID- 27202036 TI - Prospective Study on the Average Cost of Therapy for Bronchial Asthma Patients in an Indian Tertiary Care Teaching Hospital. PMID- 27202038 TI - Pharmacoeconomic Evaluation of Acute Exacerbation of Asthma in Patients in Malaysia. PMID- 27202037 TI - Pharmacoeconomic Evaluation and Burden of Illness of Acute Exacerbation of Copd in Patients in Malaysia. PMID- 27202039 TI - A Pharmacoeconomic Care Analysis of Tuberculosis Control in Pakistan. PMID- 27202040 TI - The Costs of Illness of Atopic Dermatitis in South Korea. PMID- 27202041 TI - Cost-Effectiveness of Conjugate Pneumococcal Vaccination in Romania. PMID- 27202043 TI - Cost Effectiveness of Bedaquiline for the Treatment of Multidrug-Resistant Tuberculosis. PMID- 27202042 TI - Cost-Effectiveness of a COPD Disease Management Program in Primary Care: The Recode Cluster Randomized Trial. PMID- 27202044 TI - Cost-Effectiveness Analysis of Umeclidinium Bromide Compared to Tiotropium Bromide for Symptomatic Patients with COPD in the UK. PMID- 27202045 TI - Cost Effectiveness of Umeclidinium/Vilanterol (UMEC/VI) Combination Therapy Among Symptomatic COPD Patients. PMID- 27202046 TI - Cost Effective Analysis of Dry Powdered Inhalers Versus Metered Dose Inhalers of Salbutamol for Asthma in Rural Secondary Care Hospital of South India. PMID- 27202047 TI - Cost-Effectiveness Analysis of Community-Acquired Pneumonia Treatment. PMID- 27202048 TI - Economic Evaluation of the Fixed Dose Combination of Indacaterol/ Glycopyrromium, as a Maintenance Bronchodilator Treatment in Adult Mexican Patients With COPD. PMID- 27202049 TI - Cost- Effectiveness of Real Life Asthma Pharmacotherapy. PMID- 27202050 TI - Cost-Effectiveness Analysis of High-Dose Levofloxacin Therapy of Patients With Community-Acquired Pneumonia. PMID- 27202051 TI - Cost-Effectiveness of Asthma Management in a Hospital-Based Adult Asthma Clinic in Spain. PMID- 27202052 TI - A Cost-Effectiveness Analysis of Treatment for Mild to Moderate Obstructive Sleep Apnea-Hypopnea Syndrome (OSAHS) in France. PMID- 27202053 TI - Economic Evaluation of the Use of an Infant Formula Based on Partially Hydrolyzed Serum Protein as Compared With a Standard Whole Cow's Milk Formula for Prevention of Atopic Dermatitis in Children Under 3 Years Old. PMID- 27202054 TI - Impact of Allergen Immunotherapy on Symptom-Free Days and Health Care Costs in Patients With Grass Pollen-Induced Allergic Rhinitis in Germany. PMID- 27202055 TI - Cost-Effectiveness of Subcutaneous Immunothereapy in Allergic Rhinitis Using One or More Allergens - An Analysis Long Overdue. PMID- 27202057 TI - Economic Evaluation of Omalizumab Compared With Standard Therapy in the Treatment of Severe Allergic Asthma in Adult Patients in Greece: a Cost Effectiveness Analysis Based on Clinical Trial and Real-World Data. PMID- 27202056 TI - Impact of Allergen Immunotherapy on Quality of Life and Health Care Costs in Adults and Children With Grass Pollen-Induced Allergic Rhinitis in Germany. PMID- 27202058 TI - Cost-Effectiveness Analysis of Allergen Immunotherapy in Patients With Grass Pollen-Induced Allergic Rhinitis in Spain. PMID- 27202059 TI - Cost-Effectiveness Analysis of Indacaterol/Glycopirronium (QVA149) as a Maintenance Bronchodilator Treatment in Adult Patients With Chronic Obstructive Pulmonary Disease in Spain. PMID- 27202060 TI - Cost-Effectiveness of Endobronchial Valve Therapy for Severe Emphysema: A Model Based Projection Based on the Vent Study. PMID- 27202061 TI - Can Improved Treatment of Allergic Rhinitis Improve Workplace Productivity? The Role of Intranasal Formulation of Azelastine Hydrochloride and Fluticasone Propionate (Dymista). PMID- 27202062 TI - The Potential Societal Cost Benefits of Improved Inhalation Technique With Duoresp(r) Spiromax(r) (Budesonide + Formoterol Fumarate Dihydrate) Compared With Symbicort(r) Turbuhaler(r) for the Management of Asthma and Chronic Obstructive Pulmonary Disease in Sweden. PMID- 27202063 TI - Tecepoc II Study. How to Improve the Inhalation Techniques in Patient with Copd. The Influence of Preferences. PMID- 27202064 TI - Medium Term Avoided Costs: High-Dose Hypoallergenic House Dust Mite Preparation Immunotherapy Verse Conventional Symptomatic Treatment. PMID- 27202065 TI - Device Handling Errors and the Impact on Quality of Life and Health Care Resource Use in Asthmatic Patients. PMID- 27202066 TI - Establishing the Relationship of Inhaler Satisfaction, Adherence, Smoking History and Allergic Rhinitis With Patient Outcomes: Real World Observations in US Adult Asthma Patients. PMID- 27202067 TI - Impact of Omalizumab On All-Cause and Asthma-Related Health Care Resource Utilisation in Patients With Moderate or Severe Persistent Asthma. PMID- 27202068 TI - Inhalation Technique Evolution After Training in Copd. The Role of the Device. PMID- 27202069 TI - Identification of Dry Powder Inhaler Attributes, and their Relative Importance to Asthma and Chronic Obstructive Pulmonary Disease Patients, to Inform a Discrete Choice Experiment. PMID- 27202071 TI - Translation and Linguistic Validation of Two COPD Symptom Diaries (Nicsi And Emsci) for Use in 14 Countries. PMID- 27202072 TI - Testing E-PRO Device Usability During the Translation Process: A Case Study of the Exact in 7 Countries. PMID- 27202070 TI - Symptom Burden and Health Related Quality of Life in Patients With Idiopathic Pulmonary Fibrosis in Clinical Practice: Insights-Ipf Registry. PMID- 27202073 TI - Health-Related Quality of Life Among Tuberculosis Patients in Pakistan: A Cross Sectional Study Using WHOQOL-BREF. PMID- 27202075 TI - Health-Related Quality of Life (HRQOL) in Patients With Idiopathic Pulmonary Fibrosis. PMID- 27202074 TI - A Comparison of The Reliability and Validity of the Four-Item and Six-Item NISCI Symptom Summary Scores. PMID- 27202076 TI - Asthma and Copd In Spain: Quality of Life and Health Consumption Resources. PMID- 27202077 TI - Health Related Quality of Life Among Young Smokers. PMID- 27202078 TI - Health Related Quality of Life And Health Care Utilization in Primary Care Patients With Moderate/Persistent Severity Asthma. PMID- 27202079 TI - Evaluation of Selected Ken-Drgs in Greek Public Hospitals: The Degree to Which they Reflect Actual Expenditure and Average Length of Stay. PMID- 27202080 TI - Impact of Non-Consented Switch and Subsequent Switch in Asthma Medication: Qualitative Study of Patient Perspective in the UK. PMID- 27202081 TI - Prospective Study on Quality of Life (QOL) of Bronchial Asthma Patients in a Tertiary Care Teaching Hospital. PMID- 27202082 TI - Systematic Literature Review Assessing Data on the Burden of Allergic Rhinitis from a Cost and Quality of Life Perspective. PMID- 27202083 TI - Patterns of Asthma Treatment Utilization in Newly Diagnosed Elderly Patients are Inconsistent With Asthma Management Guidelines. PMID- 27202084 TI - Determination of Availability of Antimicrobial Preparations for Treatment of Community-Acquired Pneumonia in Ukraine. PMID- 27202085 TI - Monte-Carlo Simulation to Estimate the Health Care Costs Avoided With Fluticasone Furoate/Vilanterol Due to Exacerbation Rate Reduction in Spanish COPD Patients. PMID- 27202086 TI - Sustainable Policy: Higher Medication Use & Adherence During Reimbursement of Pharmacologic Smoking Cessation Treatments. PMID- 27202087 TI - Social Media Meets Population Health: A Sentiment And Demographic Analysis of Tobacco and E-Cigarette Use Across The "Twittersphere". PMID- 27202088 TI - Doctors' Failure in Observance of the COPD Management Guidelines: Case of the CZECH Republic. PMID- 27202089 TI - How Much the Appropriate Tobacco Price Would Be?: A Discrete Choice Experiment of General Public in Japan. PMID- 27202090 TI - Efficacy of Treatments for Macular Oedema Secondary to Branch Retinal Vein Occlusion: A Network Meta-Analysis. PMID- 27202091 TI - Comparative Effectiveness of An Acellular Synthetic Matrix As An Adjunct to Standard Care In The Treatment of Venous And Mixed Leg Ulcers: Modeling of Clinical Data And Routine Data. PMID- 27202092 TI - Cost-Effectiveness of Omalizumab in Chronic Idiopathic Urticaria Refractory to H1 Antihistamines in Turkey. PMID- 27202093 TI - Outcomes of Patients With Neovascular Age-Related Macular Degeneration (Namd) In Greece Under Ranibizumab. PMID- 27202094 TI - Results of A Decubitus Prevention and Wound Care Project. PMID- 27202095 TI - Knowledge and Perception of Medical and Pharmacy Students Toward The Usage of Sunblock. PMID- 27202096 TI - Pharmacoepidemiology of Cellular/Tissue Derived Products for the Treatment of Venous Leg Ulcers in Outpatient Care Settings. PMID- 27202097 TI - The Epidemiology of Medical Treatment for Glaucoma and Ocular Hypertension in Germany. PMID- 27202098 TI - A Us Hospital Economic Impact Model for Oritavancin In Absssi Patients With Risk of Mrsa Infections. PMID- 27202099 TI - Clinical Effectiveness of Fumaric Acid Esters (Fumaderm) in Psoriasis: A Systematic Review of Literature. PMID- 27202100 TI - Economic Impact of Visual Impairment: A Pilot Study in Singapore. PMID- 27202101 TI - Costs of Burn Care: A Systematic Review. PMID- 27202102 TI - Costs of Psoriasis in Europe. A Systematic Review of the Literature. PMID- 27202103 TI - Economic Burden of Eye Disease in Diabetic Patients: Literature Review. PMID- 27202104 TI - Cost-Analysis of Chronic Idiopathic Urticaria Disease. PMID- 27202105 TI - The Direct and Indirect Costs of Wet Age-Related Macular Degeneration (Wamd) and Diabetic Macular Edema (Dme) in Greece. PMID- 27202106 TI - Economic Burden of Burn Injuries in the Netherlands. PMID- 27202107 TI - Modeled Outcomes and Overall Costs of the 13-Valent Pneumococcal Conjugate Vaccine in the Tunisian National Vaccination Program. PMID- 27202109 TI - Cost-of-Illness Study of Senile Cataract in the Czech Republic. PMID- 27202108 TI - The Cost of Blindness in the Republic of Ireland 2010-2020. PMID- 27202110 TI - Costs of Dental Outpatient Care - Resource Use Differentials Across Clinical Dentistry Branches. PMID- 27202111 TI - Cost-Effectiveness Analysis of Ustekinumab Compared With Etanercept for the Treatment of Moderate to Severe Psoriasis in Costa Rica. PMID- 27202113 TI - Ranibizumab for the Treatment of Visual Impairment Due to Myopic Choroidal Neovascularization: Cost-Effectiveness Versus Aflibercept. PMID- 27202112 TI - Cost-Effectiveness of Ranibizumab on Patients With Diffuse Diabetic Macular Edema Within the Public Mexican Health Care System. PMID- 27202114 TI - Cost-Effectiveness of Aflibercept in the Treatment of Macular Oedema Secondary to Central Retinal Vein Occlusion In Sweden. PMID- 27202115 TI - Cost-Effectiveness of Laser Doppler Imaging in Burn Care in The Netherlands; A Randomised Controlled Trial. PMID- 27202116 TI - Cost-Effectiveness of 13-Valent Versus 10-Valent Pneumococcal Conjugate Vaccine Use in Croatia National Vaccination Program. PMID- 27202117 TI - Cost-Effectiveness Analysis of Ingenolo Mebutato Verse Imiquimod in the Treatment of Actinic Keratoses in the Perspective of the Italian Health System. PMID- 27202118 TI - The Future Health Economic Potential of Next Generation Artificial Vision Devices for Treating Blindness in Germany: an Early Cost-Utility Assessment. PMID- 27202119 TI - Cost-Effectiveness of Ranibizumab Versus Photodynamic Therapy for the Treatment of Neovascluar Age-Related Macular Degeneration Based in China Cost Setting. PMID- 27202120 TI - Cost-Utility Analysis of Recommended Ranibizumab Regimen for Age-Related Macular Degeneration in China. PMID- 27202121 TI - Non-Proliferative Diabetic Retinopathy: is It Cost-Effective to Treat Early? PMID- 27202122 TI - Cost-Utility Analysis (Cua) of First-Line Actinic Keratosis (Ak) Treatments in Finland. PMID- 27202123 TI - Cost-Effectiveness of Ranibizumab Verse Aflibercept in Treatment of Treatment of Visual Impairment Due to Diabetic Macular Oedema (Dmo). PMID- 27202124 TI - Health State Utilities for Pressure Ulcers - A Comparison of Condition-Specific and Generic Measures and Time-Trade-Off (Tto). PMID- 27202125 TI - Medication Adherence and Discontinuation Predicted by Disease Duration in Glaucoma Patients: Findings From A Cross-Sectional Study in Korea. PMID- 27202126 TI - Drug Survival Rates And Cost of Biological Agents for the Treatment of Moderate to Severe Psoriasis in the Balearic Islands (Spain). PMID- 27202127 TI - Implications for Time Savings Using New Intraoperative Measuring Technology. PMID- 27202128 TI - Estimating Utility Data for Patient Symptom Severity in Chronic Spontaneous Urticaria. PMID- 27202129 TI - Health Related Quality of Life in Patients With Actinic Keratosis - Results From Patients Treated in Dermatology Specialist Care In Denmark. PMID- 27202130 TI - Categorical Health States In Chronic Spontaneous Urticaria (Csu) Based On The Weekly Urticaria Activity Score (Uas7): Are They Distinct, Discriminative, And Reproducible? PMID- 27202131 TI - The Burden Of Primary Hyperhidrosis On The Patient: Eq-5d-5l Utilities, Willingness To Pay And Daily Time Spent In Managing The Condition. PMID- 27202132 TI - Subjective Expectations Regarding Life Expectancy And Health-Related Quality Of Life In Moderate To Severe Psoriasis Patients. PMID- 27202134 TI - The Decision Making Process In Receiving Bone Conduction Implants (Bci) For Single Sided Deafness. PMID- 27202133 TI - The Burden Of Chronic Urticaria In Europe: A Systematic Literature Review. PMID- 27202135 TI - A Review Of Patient Reported Outcomes (Pros) In Psoriasis According To The Food And Drug Administration (Fda) Pro Guidance Criteria. PMID- 27202136 TI - Factors Conditioning Health Related Quality Of Life In Patients With Psoriasis In Europe: A Systematic Review Of The Literature. PMID- 27202137 TI - How Can the Quality of Life in Hand Eczema Questionnaire (qolheq) be Interpreted? A Banding Study. PMID- 27202138 TI - Cost-Effectiveness and Value of Information Analyses of Nutritional Support in Preventing Pressure Ulcers in High Risk Hospitalised Patients. PMID- 27202139 TI - Current Management and Barriers to Treatment for Wet Age-Related Macular Degeneration (Wamd): Perspectives From Patients and Caregivers. PMID- 27202140 TI - A Comaprative Cross-Sectional Study On Health-Related Quality Of Life In Psoriasis From Hungary And Iran. PMID- 27202141 TI - Dental Care Use And Associated Factors Among People With Rheumatoid Arthritis: A Nationwide, Population-Based, Propensity Score-Matched Follow-Up Study. PMID- 27202142 TI - The Analysis of Dental Care in Ukraine at the Regional Level. PMID- 27202143 TI - Fabrication Of Voriconazole Solid Lipid Nanoparticles For Effective Ocular Delivery. PMID- 27202144 TI - Understanding Trends In Ophthalmologist Patient Selection And Care Based On Patterns Of Billing. PMID- 27202145 TI - The Impact of the German Drg-System on Policy Decision Making in Ent. PMID- 27202146 TI - Macular Oedema Due to Retinal Vein Occlusion Methods for the Identification of Treatment Guidelines and Areas of Unmet Clinical Needs by Means of Systematic Review. PMID- 27202147 TI - Ophthalmology: Therapy Trends in Europe Based on Clinical Trial Registry Data. PMID- 27202148 TI - Treatment Patterns and Health Outcomes Among Patients with Radioiodine-Refractory Differentiated Thyroid Cancer in the United States and Western Europe. PMID- 27202149 TI - Approving Drugs Based on Early Stage Data - How Phase II Trial Data Correlates with Phase III Outcomes. Case Study: NSCLC. PMID- 27202150 TI - Cervical Human Papilloma Virus (HPV) DNA Primary Screening Test Results of the Experience of a Regional Laboratory in Central Italy. PMID- 27202151 TI - Comparative Effectiveness of Treatments for Relapsed or Refractory Mantle Cell Lymphoma (R/R MCL), Using Matching Adjusted Indirect Comparison. PMID- 27202152 TI - Systematic Review of Relapsed or Refractory Mantle Cell Lymphoma (MCL) Clinical Trials: Implications for Decision Modeling. PMID- 27202153 TI - Health Care Costs in Patients Treated with Ipilimumab for Advanced Melanoma Results of a Retrospective Chart Review. PMID- 27202154 TI - Treatments for EGFR Mutation-Positive (M+) NSCLC Patients - A Network Meta Analysis (NMA) by Mutation Type. PMID- 27202155 TI - Overall Survival in Patients with HER2+ Early Stage Breast Cancer Patients Treated with Trastuzumab in the US Department of Defense Practice Setting. PMID- 27202156 TI - The Relative Efficacy of Treatments in First-Line Management of Newly Diagnosed Chronic Myeloid Leukaemia: Systematic Literature Review and Indirect Comparison. PMID- 27202157 TI - An Indirect Treatment Comparison of Cabozantinib Verse Vandetanib in Progressive Medullary Thyroid Cancer (MTC). PMID- 27202158 TI - Analysis of Treatment Options for Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL). PMID- 27202159 TI - Clinical Effectiveness of Robotic Image-Guided Stereotactic Radiosurgery (CyberKnife) in Selected Primary and Secondary Soft Tissue Neoplasms: A Systematic Review. PMID- 27202160 TI - Comparison of Mean Overall Survival (OS) and Radiographic Progression Free Survival (RPFS) Based on Matching Adjusted Indirect Comparison of Abiraterone Acetate and Enzalutamide for the Treatment of Castration-Resistant Prostate Cancer in Chemotherapy Naive Patients. PMID- 27202161 TI - The Efficacy of Current Treatment Options for Metastatic Cervical Cancer. PMID- 27202163 TI - A Systematic Literature Review to Identify Trials in First-Line Ras Wild-Type (WT) Metastatic Colorectal Cancer (MCRC) Patients. PMID- 27202162 TI - Bortezomib Re-treatment in Patients with Multiple Myeloma (MM). A Real World Medical Practice Experience from a Swedish National Registry. PMID- 27202164 TI - Characteristics of Patients with Pleural Mesothelioma in the Russian Federation. PMID- 27202165 TI - First-Line Therapy for Patients With Multiple Myeloma: Direct and Indirect Comparison of Treatment Regimens on the Existing Market. PMID- 27202166 TI - What is the Clinical Effectiveness and Cost- Effectiveness of Erythropoietin Stimulating Agents for the Treatment of Patients with Cancer-Treatment Induced Anaemia? Insights from Cumulative Meta-Analyses (CMA) and Lessons for Cost Effectiveness Analyses. PMID- 27202167 TI - Treatment Sequencing Survival Model for Patients with Multiple Myeloma Ineligible for Stem Cell Transplantation (SCT). PMID- 27202168 TI - The Importance of Long-Term Surveillance of Stage IB Melanomas: Unexpectedly Low Survival Subsequent to Recurrence. PMID- 27202170 TI - Long-Term Trends in Breast Cancer Epidemiology in the Slovak Republic. PMID- 27202169 TI - Real-World Data on the Epidemiology and Treatment of HR +, HER2-Advanced Breast Cancer in Postmenopausal Patients in Different Regions of Russia for Forming Markov Models of Managment of Patients. PMID- 27202171 TI - Projecting Health Gains: The Population Impact of New Treatments to Metastatic Breast Cancer. PMID- 27202172 TI - Burden of Disease in Stage IV Non-Small Cell Lung Cancer: Comparing ALK Positive and ALK Negative Mutation Status in Egypt, Russia and the United Arab Emirates. PMID- 27202173 TI - Epidemiology of Patients with Metastatic Castrate Resistant Prostate Cancer in Europe and Australia. PMID- 27202174 TI - Comparison of Epidemiology and Drug Treatment in HER2 Negative Metastatic Breast Cancer (MBC) in EU5. PMID- 27202175 TI - Association of Diabetes and Cancer Diagnosis in Primary Care Practices in France. PMID- 27202176 TI - A Validated Prediction Model and Nomogram for Risk of Recurrence in Early Breast Cancer Patients. PMID- 27202177 TI - Patient Count Projections for Advanced Melanoma by Line of Therapy and Other Clinical Characteristics in EU Countries: Results from The UK, Germany, France, Italy and Spain (EU-5). PMID- 27202178 TI - Long Term Survival of Patients with Various Lung Cancer Histology in Seer Between 2004-2011. PMID- 27202179 TI - Impact of Hospital Volume on Breast Cancer Outcome: A Population Based Study in the Netherlands. PMID- 27202180 TI - Simulation Model of Ibrutinib in Treatment of Relapsed or Refractory Mantle Cell Lymphoma (MCL). PMID- 27202181 TI - The Benefit of Her-2 Targeted Therapies on Overall Survival of Patients With Metastatic Breast Cancer - A Systematic Review. PMID- 27202182 TI - Simulation Model of Ibrutinib for Chronic Lymphocytic Leukemia (CLL) With Prior Treatment. PMID- 27202183 TI - Survival After Locoregional Recurrence or Second Primary Breast Cancer: Impact of the Disease-Free Interval. PMID- 27202184 TI - Estimating the Economic Impact of Sorafenib in Treatment of Locally Recurrent or Metastatic, Progressive, Differentiated Thyroid Carcinoma (DTC) That is Refractory to Radioactive Iodine (RAI) Treatment. PMID- 27202185 TI - Budget Impact Analysis of Aflibercept in yhe Treatment of Metastatic Colorectal Cancer (MCRC) in Poland. PMID- 27202186 TI - Forecasting Outpatient Pharmaceutical Expenditure for Cancer Treatment in Germany. PMID- 27202187 TI - Budget Impact Analysis of Everolimus for the Treatment of Hormone Receptor Positive, Human Epidermal Growth Factor Receptor-2 Negative (HER2-) Advanced Breast Cancer in Kazakhstan. PMID- 27202188 TI - Budget Impact Analysis of CYP2C19 Genotyping to Target Voriconazole Prophylaxis During Induction-Consolidation Therapy in Acute Myeloid Leukemia (AML) in The United States. PMID- 27202189 TI - Budget Impact Analysis of the Introduction of New Therapeutic Agents for the Treatment of Metastatic Castration Resistant Prostate Cancer (MCRPC) Patients After Docetaxel Failure in the Brazilian Private Health System. PMID- 27202190 TI - Buget Impact Analysis of Rituximab for Chronic Lymphocytic Leukemic: The Case of Brazilian Public Health. PMID- 27202192 TI - Budget Impact Analysis of the Use of Crizotinib for Non-Small Cell Lung Cancer and ALK+ Mutation in the Two Main Public Health Care Institutions in Mexico. PMID- 27202191 TI - Budget Impact Analysis of Everolimus Plus Exemestane Versus Gemcitabine Plus Paclitaxel and Capecitabine Plus Docetaxel in Metastatic Breast Cancer Patients in Egypt. PMID- 27202193 TI - Budget Impact Model of Ceplene(r) As Maintenance Therapy in Adult Patients with Acute Myeloid Leukemia in First Remission. PMID- 27202194 TI - Real-World Costs of Laboratory Tests for Non-Small Cell Lung Cancer. PMID- 27202195 TI - Positron Emission Tomography/Computed Tomography Imaging for Non-Small Cell Lung Cancer: A Budget Impact Analysis. PMID- 27202196 TI - Budget Impact and Incremental Survival Benefit of Eribulin Mesylate as a Treatment for Metastatic Breast Cancer in Brazil. PMID- 27202197 TI - Budget Impact on the Use of Pegfilgrastim to Reduce the Febrile Neutropenia During Chemotherapy for Breast Cancer with Moderate Risk Compared to a Standard Therapy. PMID- 27202198 TI - Costs of Pneumonia in Patients With Cancer Diagnosis from the Private Health System Perspective in Brazil. PMID- 27202199 TI - Economic Impact of a Genomic Companion Diagnostic Test for Breast Cancer Patients in French Private Hospitals. PMID- 27202200 TI - Cost-Effectiveness and Budget-Impact Analysis of Braf Inhibitors in Patients With Metastatic Malignant Melanoma (MMM) in Slovenia. PMID- 27202201 TI - Budget Impact Analysis of a Return-To-Work Intervention for Cancer Patients Shows Hospitals Bear the Costs, for Society to Enjoy the Benefits. PMID- 27202202 TI - Cost of Treating Acute Promyelocytic Leukemia (APL) Patients in Italy. PMID- 27202204 TI - Costed Treatment Pathways of Diffuse Large B Cell Lymphoma in a UK Population Based Cohort: A Patient Level Simulation Model. PMID- 27202203 TI - Economic Impact of Centralized Histological Reviews in Patients with Sarcoma, Gist, and Desmoid Tumors. PMID- 27202206 TI - Cost-Consequence Analysis of an Aprepitant Regimen Versus a Standard Antiemetic Regimen for the Prevention of Highly Emetogenic Chemotherapy-Induced Nausea and Vomiting in Italy. PMID- 27202205 TI - A Cost-Analysis of Complex Radiotherapy in Patients with Head and Neck Cancer Results from the Art-Orl Study. PMID- 27202207 TI - Cost of Non Small Cell Lung Cancer by Vietnamese and European Treatment Standards in Vietnam. PMID- 27202208 TI - Hospital Cost of Thromboembolic Events in Breast or Prostate Cancer Patients. PMID- 27202209 TI - Assessing the Economic Burden and Health Care Utilization of U. S. Medicare Patients Diagnosed with Melanoma. PMID- 27202210 TI - Resource Use and Health Care Costs of Cervical Lesions and Cervical Cancer in Slovakia. PMID- 27202211 TI - Economic Burden of Melanoma in Three European Countries: A Retrospective Observational Study. PMID- 27202212 TI - Cost and Burden of Non-Small Cell Lung Cancer's in Portugal. PMID- 27202213 TI - Metastatic Prostate Cancer and Skeletal Related Events, a Cost of Illness Study. PMID- 27202214 TI - Economic Impact Model of Breast Cancer Treatment at Early Stages in the Mexican Public Health Care Sector. PMID- 27202215 TI - The Burden of Non-Small Cells Lung Cancer (NSCLC) in First Line (1L) Treatment: Patterns of Care and Cost of Illness. PMID- 27202216 TI - Burden of Prostate Cancer and Future Need for Health Care Services. PMID- 27202217 TI - Economic Burden of Asthma in Vietnam: An Analysis from Patients' Perspective. PMID- 27202218 TI - Burden of Disease of the Mastacarcinoma in Austria. PMID- 27202219 TI - Economic Burden of Disease in France In 2012: A Top-Down Allocation of Health Care Expenditure by Disease Based on the French Health insurance Database (SNIIRAM). PMID- 27202220 TI - The Burden of Health Care Costs Associated with Prostate Cancer in Ireland. PMID- 27202221 TI - Health Care Costs and Utilization of U. S. Veteran Patients Diagnosed with Pancreatic Cancer. PMID- 27202222 TI - Real World Management and Costs in Unresectable Metastatic Melanoma (UMM) Patients Treated at the Antwerp University Hospital (UZA). PMID- 27202223 TI - Economic Burden of Chemotherapy Related Toxicities in Third Line Metastatic Breast Cancer Patients. PMID- 27202224 TI - The Cost of NSCLC Treatment in Three Countries: France, Germany and UK. PMID- 27202225 TI - Trends in Secondary Care Costs for Treatment of Head and Neck Cancer in England. PMID- 27202226 TI - A Systematic Literature Review of the Economic Burden in Multiple Myeloma. PMID- 27202227 TI - Exploring the Usefulness of Social Media and Patient Forums in Identifying indirect Costs of a Disease. PMID- 27202228 TI - Mastectomy Due to Breast Cancer in Brazil: Geographic Distribution and Costs from the Public Health Care Perspective. PMID- 27202229 TI - Estimation of Economic Losses Resulting from Diseases Associated with Smoking in Mexican Insured and Uninsured Population. PMID- 27202230 TI - Cost Comparison Among First Line Monoclonal Antibodies-Based Oncology Treatment Protocols. PMID- 27202231 TI - A Guideline-Based Estimate of Health Care Resource Use and Cost of Metastatic Unresectable Osteosarcoma. PMID- 27202232 TI - Use Patterns and Costs of Isolated Limb Perfusion and Infusion in the Treatment of Regionally Metastatic Melanoma: A Retrospective Database Analysis. PMID- 27202233 TI - Cost of Best Supportive Care for Non-Small Cell Lung Cancer Patients - A German Perspective. PMID- 27202234 TI - Resource Use and Health Care Costs of Metastatic Malignant Melanoma in Slovakia. PMID- 27202235 TI - Cost-Benefit Assessment of the Electronic Health Records for Clinical Research (EHR4CR) European Project. PMID- 27202236 TI - Cost-Effectiveness of Colonic Stents for the Management of Malignant Large Bowel Obstruction. PMID- 27202237 TI - A Multi-State Model of Metatstatic Colorectal Cancer. PMID- 27202239 TI - Cost Consequence Model Investigating the Impact of Bowel Cleansing on Prevention of Colorectal Cancer in a German Screening Population. PMID- 27202238 TI - Economic Consequences of the Adaption of the 21 Gene Reverse Transcriptase Polymerase Chain Reaction RT-PCR Assay from The Greek Third Payer Perspective. PMID- 27202240 TI - A Cost-Consequence Analysis of Human Papillomavirus Vaccination in Romania. PMID- 27202241 TI - Association of Health Care Cost with Quality of Life for Various Types of Cancers. PMID- 27202242 TI - Cost-Effectiveness Model of Pertuzumab in Combination with Trastuzumab and Docetaxel Compared with Trastuzumab in Combination with Docetaxel for the 1st Line Treatment of HER2+ Metastatic Breast Cancer in Colombia. PMID- 27202243 TI - Cost-Effectiveness of Ipilimumab for Previously Untreated Patients with Advanced Metastatic Melanoma in Spain. PMID- 27202244 TI - The Potential of (TARGETED) MR Colonography as a Screening Tool for Colorectal Cancer: A Cost-Effectiveness Analysis. PMID- 27202245 TI - Everolimus Plus Exemestane Compared to Exemestane and Fulvestrant for the Treatment of ER+ HER2- Metastastic Breast Cancer in the United Kingdom - A Societal Perspective. PMID- 27202246 TI - Economic Evaluation of NAB-Paclitaxel Plus Gemcitabine Versus Gemcitabine Alone for The Management of Metastatic Pancreatic Cancer in Greece. PMID- 27202247 TI - Cost-Effectiveness Analysis of Panitumumab Plus Mfolfox6 Versus Bevacizumab Plus Mfolfox6 for First-Line Treatment of Patients with Wild-Type Ras Metastatic Colorectal Cancer. PMID- 27202248 TI - Cost-Effectiveness Analysis of Abiraterone Acetate Treatment Compared with Cabacitaxel in the Republic of Panama, in Patients with Metastatic Castration Resistant Prostate Cancer that Have Failed to Chemotherapy with Docetaxel. PMID- 27202249 TI - Cost-Utility Analysis of Pazopanib Verse Sunitinib as First-Line Treatment of Metastatic Renal Cell Carcinoma (MRCC) iN Spain. PMID- 27202250 TI - Economic Evaluation of the Use of Gefitinib for the Treatment of Locally Advanced or Metastatic NSCLC. PMID- 27202251 TI - Cost-Effectiveness of Ofatumumab Plus Chlorambucil in First Line Chronic Lymphocytic Leukemia in Canada. PMID- 27202252 TI - Cost-Effectiveness Analysis of Panitumumab+Mfolfox over Bevacizumab+Mfolfox as a First-Line Treatment for Metastatic Colorectal Cancer Patients with Wild-Type Ras in Greece. PMID- 27202253 TI - Cost-Effectiveness and Cost-Utility of Granulocyte Colony-Stimulating Factors in the Primary Prophylaxis of Chemotherapy Induced Febrile Neutropenia (FN) in Breast Cancer Patients in Greece: A Comparative Analysis. PMID- 27202254 TI - Cost-Effectiveness of Vismodegib Verse Standard of Care Therapy in the Treatment of Locally-Advanced or Symptomatic Metastatic Basal Cell Carcinoma in Hungary - A Global Cost-Effectiveness Model Adaptation. PMID- 27202255 TI - Cost-Effectiveness of Aprepitant in Egyptian Patients Receiving Highly Emetogenic Therapy from the Third Party Payer Perspective. PMID- 27202256 TI - Cost Effectiveness Analysis of Everolimus + Exemestane for Patients with Advanced Breast Cancer with Positive Estrogen Receptor (ER +), HER2-, Refractory to Non Steroidal Aromatase Inhibitors (NSAIS) in Chile. PMID- 27202257 TI - Cost-Effectiveness of 2-DOSE AS04-Adjuvanted Human Papillomavirus 16/18 Vaccination Schedule in Slovakia. PMID- 27202258 TI - Cost-Effectiveness Analysis of Bevacizumab- Paclitaxel-Carboplatin (PC) Versus PC in First-Line Therapy of Advanced Non-Small Cell Lung Cancer from Patients' Perspective in Vietnam. PMID- 27202259 TI - Potential Monetary Value of Human Papillomavirus Vaccination on Human Papillomavirus-Related Cancers and Genital Warts in the United Kingdom. PMID- 27202260 TI - A Cost Effectiveness Analysis of Everolimus Plus Exemestane Compared to Chemotherapy Agents for the Treatment of ER+ HER2- Metastastic Breast Cancer in the United Kingdom. PMID- 27202261 TI - Cost-Effectiveness Analysis of Abiraterone Acetate Treatment Compared with Cabacitaxel in Dominican Republic, in Patients With Metastatic Castration Resistant Prostate Cancer that Have Failed to Chemotherapy with Docetaxel. PMID- 27202262 TI - Cost-Effectiveness Analysis of Abiraterone Acetate Treatment Compared With Cabacitaxel in Costa Rica, in Patients with Metastatic Castration-Resistant Prostate Cancer That Have Failed to Chemotherapy with Docetaxel. PMID- 27202263 TI - Cost-Effectiveness Simulation of Colonography Versus Colonoscopy in Germany: Is Laxative-Free Colonography Cost-Effective? PMID- 27202264 TI - Clinical and Economic Analysis of Effectiveness of Everolimus in the Treatment Of HR+, HER2- Advanced Breast Cancer in Russia. PMID- 27202265 TI - A Cost-Effectiveness Analysis of EGFR-TK Mutation Status-Guided 1st- and 2nd-Line Treatment of Stage III/IV Non-Small Cell Lung Cancer in the UK. PMID- 27202266 TI - Comparative Cost-Effectiveness Study of Modern Radiation Therapies in Hungary for Localized Prostate Cancer. PMID- 27202267 TI - Systematic Critical Review of Economic Evaluations of Rituximab, Added to Conventional Chemotherapy Regimen in the Treatment of Patients with Chronic Lymphocytic Leukemic Refractory. PMID- 27202268 TI - Literature Review of Decision-Analytical Models Used in the Economic Evaluation of Empirical/Targeted Antifungal Treatments for Invasive Fungal Infections. PMID- 27202269 TI - What is the Most Cost-Effective Strategy for Treating Chronic Myeloid Leukemia After Imatinib Loses Patent Exclusivity in Europe? PMID- 27202270 TI - Cost-Effectiveness of Radical Prostatectomy, Radiation Therapy and Active Surveillance for the Treatment of Localized Prostate Cancer - A Claims Data Analysis. PMID- 27202271 TI - Expansion of the Norwegian HPV Vaccination Program. PMID- 27202272 TI - Cost-Effectiveness Evaluation of Brentuximab Vedotin for Refractory/Relapsed Hodgkin Lymphoma: A Comparative Analysis of the Results of Mexico and Venezuela. PMID- 27202273 TI - Critical Review of Cost-Effectiveness Analyses (CEA) of Prevention Strategies Against Diseases Associated with Human Papillomavirus (HPV) Infection. PMID- 27202274 TI - Cost-Effectiveness Analysis of Fulvestrant in the Treatment of Metastatic Breast Cancer in Second-Line Chemotherapy. PMID- 27202276 TI - Economic Evaluetion of Fulvestrant 500 MG (F500) Versus Original Nonsteroidal Aromatase Inhibitors in Patient with Advanced Breast Canser in Russia (2 LINE THERAPY). PMID- 27202275 TI - Will Governments be Able to Afford a Cancer Cure Under Current Health Economic Evaluation Methods? PMID- 27202277 TI - Economic Impact of the Inclusion of Pertuzumab for the Treatment of Metastatic Breast Cancer HER2. PMID- 27202278 TI - Cost Effectiveness of Sunitinib as First-Line Targeted Therapy for Metastatic Renal Cell Carcinoma in China. PMID- 27202279 TI - Cost-Effectiveness Analysis of Bevacizumab, Fotemustine and Extended-Dose Temozolomide in Patients with Recurrent Glioblastoma in Spain. PMID- 27202280 TI - Cost Effectiveness of Cetuximab in 1st-Line Treatment of RAS Wild-Type Metastatic Colorectal Cancer in Scotland: A Summary of the Submission to the Scottish Medicines Consortium. PMID- 27202281 TI - An Evidence-Based Model Design to Inform the Cost-Effectiveness Evaluation of Primary Endocrine Therapy And Surgery for Older Women with Primary Breast Cancer. PMID- 27202282 TI - Pharmacoeconomic Analysis of Axitinib as Second-Line Treatment for Metastatic Renal Cell Carcinoma. PMID- 27202283 TI - Decision Analysis on the Cost-Effectiveness of Sequential Treatment Strategies for Patients with Chronic Myeloid Leukemia in the United States. PMID- 27202284 TI - Prioritization of Future Outcomes Research Studies in Chronic Myeloid Leukemia: Value of Information Analysis. PMID- 27202285 TI - Cost-Effectiveness Analysis of Hydralazine and Magnesium Valproate LP Associated With Treatment for Adult Patients with Metastatic Recurrent or Persistent Cervical Cancer in Mexico. PMID- 27202286 TI - The Cost-Effectiveness of Brentuximab Vedotin in Hodgkin Lymphoma in Sweden. PMID- 27202287 TI - Economic Evaluation of Axitinib for Second Line Treatment in Adult Patients with Advanced Renal Cell Carcinoma - the Portuguese Case. PMID- 27202288 TI - Cost Effectiveness Analysis of Targeted Intraoperative Radiotherapy Alone (TARGIT A) in Early Breast Cancer Patients. PMID- 27202289 TI - Cost-Minimization Analysis of Trastuzumab Intravenous Versus Trastuzumab Subcutaneous for the Treatment of Patients With HER2+ Early Breast Cancer And Metastatic Breast Cancer in Greece. PMID- 27202290 TI - A Cost Effectivness Analysis of Everolimus Compared with Axitinib in the Treatment of Metastatic Renal Cell Carcinoma in the United Kingdom. PMID- 27202291 TI - Early Cost-Effectiveness Modeling for Tumor Infiltrating Lymphocytes (TIL) Treatment Versus Ipilimumab in Metastatic Melanoma Patients. PMID- 27202292 TI - Economic Evaluation of Paclitaxel Albumin, Paclitaxel, and Docetaxel as a Second Line Treatment for Metastatic Breast Cancer. PMID- 27202293 TI - Cost-Minimization Analysis of Bevacizumab Verse Cetuximab in First-Line Treatment for Metastatic Colorectal Cancer in Kras Wild-Type Patients in the Supplementary Health Care System in Brazil. PMID- 27202294 TI - Model-Based Cost-Utility Analysis of Erythropoiesis-Stimulating Agents for the Treatment of Cancer-Treatment Induced Anaemia in the UK NHS. PMID- 27202295 TI - 'DE NOVO' Quantification of Genotype-Directed Therapy with Afatinib in Metastatic Lung Cancer. PMID- 27202296 TI - Cost-Effectiveness Analysis of Bendamustin-Rituximab Compared to Chop-Rituximab in the Treatment of Indolent Follicular Non-Hodgkin Lymhoma in the Czech Republic. PMID- 27202297 TI - Pharmacoeconomic Analysis of Oral Capecitabine and Tegafur for Colorectal Cancer Treatment in Russia. PMID- 27202298 TI - Economic Impact of Using Subcutaneous Trastuzumab. PMID- 27202299 TI - Economic Evaluation of Lapatinib in Her-2-Positive Metastatic Breast Cancer Patients in Egypt. PMID- 27202300 TI - Health Care Utilization and Costs of Breast Cancer in the Medicaid Program. PMID- 27202301 TI - Nab-Paclitaxel or Docetaxel as Alternatives to Solvent-Based Paclitaxel in Metastatic Breast Cancer (Mbc): A Cost Utility Analysis from a Chinese Health Care Perspective. PMID- 27202302 TI - The Cost-Effectiveness of Second-Line Crizotinib in Eml4-Alk Rearranged Advanced Non-Small Cell Lung Cancer. PMID- 27202303 TI - Cost-Effectiveness of Ipilimumab in Previously Untreated Patients for Advanced Melanoma in Sweden. PMID- 27202304 TI - Qaly Weightings Based on the Burden of Illness Applied to a Uk Cost-Effectiveness Analysis of Nab-Paclitaxel + Gemcitabine Versus Gemcitabine Alone for the Treatment of Metastatic Pancreatic Cancer. PMID- 27202305 TI - What's the optimal visual inspection screening intervals for cervical cancer screening in real practice of rural china? A cost-utility modeling study. PMID- 27202306 TI - Economic Evaluation of Home Parenteral Nutriton in Cancer Patients; The French Context. PMID- 27202307 TI - Cost-Effectiveness Analysis of Testing for Brca Mutations in Women Diagnosed with Ovarian Cancer and their Female First-Degree Relatives: A Uk Health Service Perspective. PMID- 27202308 TI - Cost-Effectiveness Analysis of Ugt1a1 Genotyping Before Colorectal Cancer Treatment with Irinotecan. PMID- 27202309 TI - Cost-Utility Analysis of Trastuzumab in Treatment Of Metastatic Her2-Positive Breast Cancer in Vietnam. PMID- 27202310 TI - Burden of Drug Waste in Oncology: Optimization of Resource Use. PMID- 27202311 TI - Real World Data in Oncology: Third- and Fourth-Line Treatments Administered in Metastatic Colon-Rectal Cancer (MCRC). PMID- 27202312 TI - Estimating the Voi of Pivotal Studies Towards Predictive Biomarkers of High Dose Alkylating Chemotherapy in Triple Negative Breast Cancer. PMID- 27202313 TI - Burden of Renal Impairment: Relative Health Care Resource use in Prostate Cancer Patients with Bone Metastases. PMID- 27202314 TI - Resources Utilization for the Investigation of Pulmonary Nodules in a University Hospital Center in Quebec, Canada. PMID- 27202315 TI - Impact on Hospitalization Derived from the Use of Denosumab for the Prevention of Skeletal-Related Events in Patients with Bone Metastases Secondary to Breast Cancer in Germany. PMID- 27202316 TI - Amnog Benefit Assessment for Oncologic and Orphan Drugs in Germany - Implications for Price Discounts. PMID- 27202317 TI - Targeted Literature Review of Medication Event Monitoring Systems to Evaluate Adherence in Observational Real-World Studies. PMID- 27202318 TI - A Systematic Review of Health State Utility Values for Advanced Ovarian Cancer. PMID- 27202319 TI - Clinical Implementation of Genomic Sequencing in Pediatric Oncology: Identification and Valuation of Resources and Costs Associated with Next Generation Sequencing. PMID- 27202320 TI - Health-State Utility Values in Breast And Prostate Cancer Measured using the EQ 5D: A Systematic Review of the Literature. PMID- 27202321 TI - Obtaining Indirect Utilities with the Sf-6d and the Porpus-U in Prostate Cancer Patients. PMID- 27202322 TI - Health State Utility Valuation in Radio-Iodine Refractory Differentiated Thyroid Cancer (RR-DTC). PMID- 27202323 TI - French Utility Elicitation in Previously Treated European Patients with Indolent Non-Hodgkin Lymphoma (INHL). PMID- 27202324 TI - Generating Health State Utility Values from Fact-Ovarian Data Collected in a Phase Ii Maintenance Study in Platinum Sensitive Recurrent Ovarian Cancer (Study 19): A Comparison of Mapping Algorithms. PMID- 27202325 TI - Patient Satisfaction Regarding their Treatment and Disease Decisions in Infra Centimetric Breast Cancer. PMID- 27202326 TI - Health Related Quality of Life and Patient Satisfaction in Colorectal Cancer Patients Treated Through Radical Surgery in Curative Intent in a Colo-Proctology Clinical Department. PMID- 27202327 TI - Health Related Quality of Life (Hrqol) in Multiple Myeloma Patients Treated in a Tertiary Referral Hospital. PMID- 27202329 TI - Brio: A European Prospective Observational Study to Assess the Burden of Disease and Treatment in Metastatic Breast Cancer (Mbc) Patients Treated with Oral Vinorelbine (Nvboral) or Intravenous Vinorelbine (Ivvino). PMID- 27202328 TI - Public Preferences for Genetic Screening for Colorectal Cancer: A Discrete Choice Experiment. PMID- 27202330 TI - Health Related Quality of Life and Patient Satisfaction in Prostate Cancer Patients Treated Through Radical Prostatectomy. PMID- 27202331 TI - Investigating the Framing-Effects of Risk Attributes in Discrete Choice Experiments: A Pilot Study. PMID- 27202332 TI - Results and implications of using a new eq-5d value set for cost-utility analyses in sweden. An application using enzalutamide (xtandi(r)) verse best supportive care for treatment of metastatic castration resistant prostate cancer (MCRPC). PMID- 27202333 TI - Possibilities of Breast Cancer Prevention. PMID- 27202334 TI - Knowledge of Human Papillomavirus among University Students in Hungary. PMID- 27202335 TI - What Matters to Patients and their Caregivers: Using Social Media and Patient Forums to Obtain Valuable Information from a Patient and Carer Perspective. PMID- 27202336 TI - Patients' Preferences for Bone Metastases Treatments in Turkey. PMID- 27202337 TI - Patient and Disease Characteristics are Important Determinants of Health-Related Quality of Life of Patients with Metastatic Renal Cell Carcinoma Results from a Population-Based Registry. PMID- 27202338 TI - Development of a Conceptual Model for Pediatric Oncology Results from a Review of Qualitative Research Literature and Clinician Interviews. PMID- 27202339 TI - Misuse, Abuse, and Diversion of instanyl(r) (Fentanyl Nasal Spray) in France. PMID- 27202341 TI - Development of a Patient-Led End of Study Questionnaire to Evaluate the Experience of Clinical Trial Participation. PMID- 27202340 TI - Patient-Reported Outcomes Assessed Using the Breast-Q Instrument in Women Undergoing Breast Reconstruction Post-Mastectomy: A Systematic Literature Review. PMID- 27202342 TI - Skeletal-Related Events (SRES) Impact Significantly the Health-Related Quality of Life (HRQOL) of Chemo-Naive Men With Metastatic Castration Resistant Prostate Cancer (MCRPC). PMID- 27202343 TI - Patients' Priorities in the Treatment of Neuroendocrine Tumors: An Analytic Hierarchy Process. PMID- 27202344 TI - What Relapsed/Refractory Cll/Mcl Treatment Outcomes Do German Patients And Physicians Find Most Important? Results from Qualitative Interviews. PMID- 27202345 TI - Patients' Preferences in Late Stage Treatment of Non-Small-Cell Lung Cancer: A Discrete-Choice Experiment. PMID- 27202346 TI - Carer Perceived Burden as a Predictor of Health-Related Quality of Life: The Case of Colorectal Cancer. PMID- 27202347 TI - Impact of Brain Metastases on Quality of Life and Estimated Life Expectancy in Patients with Advanced Non-Small Cell Lung Cancer. PMID- 27202348 TI - Shared Decision-Making in Women with Early Stage Breast Cancer and Implications for Long-Term Health-Related Quality of Life. PMID- 27202349 TI - Validation of the Proposed Reduced Quality of Life Questionnaire to the Eortc QLQ C30 in Cubans Patients with Cancer. PMID- 27202350 TI - Quality of Life in Patients With Lung Cancer in the Slovak Republic. PMID- 27202351 TI - Quality of Life in Patients with Multiple Myeloma in Slovakia. PMID- 27202352 TI - Sustainable Measurement of Response Shift in Prostate Cancer Patients: Adjusting Health Related Quality of Life with the Then-Test. PMID- 27202353 TI - Evidence-Based Medicine as a Driver of Improving Colorectal Cancer Screening in Ukraine. PMID- 27202354 TI - 5-Year Survival is not an Appropriate Indicator for Cancer Control in the Population: Revisiting the Issue Based on UK Data. PMID- 27202355 TI - How is Research and Development Innovation Evolving? Focus on Oncology and Cardiovascular Disease. PMID- 27202356 TI - Next Generation Sequencing Technology: Health Technology Assessment, Market Access Trends and Potential Impacts on The Future of Companion Diagnostic Testing. PMID- 27202357 TI - Expert Elicitation Used for Early Technology Assessment to Inform on Cost Effectiveness of Next Generation Sequencing. PMID- 27202358 TI - A Comprehensive Assessment of Early Trial Evidence in Primary Breast Cancer: How Decisions Change Over Time. PMID- 27202359 TI - An Italian Oncology Research to Evaluate Adherence to Clinical Guidelines for Cancer Treatment: The Right Program. PMID- 27202360 TI - Which is More Important for Doctors in a Low-Middle Income Country: a National Guideline or the Medical Literature? A Guideline Adherence Survey of Trastuzumab use for Breast Cancer in iran. PMID- 27202361 TI - Time Savings With Transtuzumab Subcutaneous (SC) Injection Verse Trastuzumab Intravenous (IV) Infusion: A Time and Motion Study in 3 Russian Centers. PMID- 27202362 TI - Process Mapping to Capture Breast Cancer Patients' Journey in Greek Public Oncological Hospitals. PMID- 27202363 TI - Assessment of Lung Cancer Treatment by Disease Phase Using National Cancer Registry Data Linked with Treatment Pathway cost Data in Austria. PMID- 27202364 TI - Current Status of Reimbursement Decisions for Orphan Drugs or Cancer Drugs and Implementation for Access Schemes in Korea. PMID- 27202365 TI - Market Access Levers and Barriers for Key Oncology Agents in the EU5: Surveyed Oncologist and Interviewed Payer Insights. PMID- 27202366 TI - Pricing and Reimbursement Analysis of Bacillus Calmette-Guerin (BCG) Immunotherapy for Bladder Cancer. PMID- 27202368 TI - Impact of Introducing Costs/Qaly Threshold on Access to Oncology Medicines in Slovakia. PMID- 27202367 TI - The Expanding Value Footprint of Oncology Treatments. PMID- 27202369 TI - A Comparison of Market Access Evaluations for new Oncology Therapies in France, Germany and the UK: An Analysis Using the Prismaccess Database. PMID- 27202370 TI - The FDA Black Box Warning Does Reduce the Use of Erythropoietin Stimulating Agents and Increases Blood Transfusions in Insured, Low Income Cancer Patients. PMID- 27202371 TI - Innovation May Drive Streamlined Access to New Biopharmaceuticals Across Some Emea Markets. PMID- 27202372 TI - Treatment Patterns And Outcomes Of Patients Diagnosed With Ovarian Cancer In The Netherlands: A Registry Study. PMID- 27202373 TI - How Successful Have Pediatric Investigation Plans Been In Stimulating Research For Pediatric Cancers? PMID- 27202374 TI - Treatment Patterns and Costs Of Neoadjuvant Systemic Therapies (NAT) For Early Breast Cancer (EBC): A Retrospective Claims Analysis. PMID- 27202375 TI - Health Economic Impact of Volume Doubling Time as Biomarker in Lung Cancer Diagnosis. PMID- 27202377 TI - Differential Pharmaceutical Pricing: Are Prices Co-Related With GDP? PMID- 27202376 TI - What are the Health Care Resource Utilization and Medical Cost of Untreated Patients with Neuroendocrine Tumors in the United States? PMID- 27202378 TI - Using Innovative Modeling Analytics with Real World Data to Develop a National Breast Cancer Screening Program in the Kingdom of Saudi Arabia. PMID- 27202380 TI - Health Care Resource Utilization (HCRU) In Hospitalized Febrile Neutropenia (FN) Patients Treated With Chemotherapy For Solid Tumors (ST) And Hematological Malignancies (HM) In Bulgaria. PMID- 27202379 TI - Off-Label Use of Anticancer Drugs In South Korea. PMID- 27202382 TI - Evidence for Regional Variation in the Appraisal of Individual Cancer Drugs Fund Requests. PMID- 27202381 TI - Saudi Arabia: A very Attractive Biopharmaceutical Market, Once Manufacturers Can Navigate the Labyrinth. PMID- 27202383 TI - The UK Cancer Drug Fund Scoring System and the Impact of the Incremental Cost Effectiveness Ratio on Funding Decisions. PMID- 27202384 TI - Pharmaceutical Market Access in Russia: A Regional Maze? PMID- 27202385 TI - Health Care Resource Utilization (HCRU) In Hospitalized Febrile Neutropenia (FN) Patients Treated With Chemotherapy for Solid Tumors (ST) And Hematological Malignancies (HM) In Bulgaria (BG), Czech Republic (CZ) And Slovakia (SK) As Observed In Clinical Practice. PMID- 27202386 TI - Total Vaccine Cold Chain Volume Needed For Human Papillomavirus Vaccination In Bangladesh. PMID- 27202387 TI - Reimbursement of Targeted Cancer Therapies Within Three Different European Health Care Systems. PMID- 27202388 TI - Reimbursed Pharmacotherapy of Metastatic Clear Cell Kidney Cancer (MCCKC) in the Czech Republic. PMID- 27202389 TI - Dilemma of Cross-Over Trials and Their Impact on Benefit Assessment In Oncology. PMID- 27202390 TI - Likely Impact of Net Price Referencing on European Markets. PMID- 27202391 TI - Awareness of Breast Cancer and its Prevention. A Comparative Survey Among Finnish and Hungarian Women. PMID- 27202392 TI - Comparing Access to Drugs Through the CDF and by Nice - The CDF Stipulate Stricter Clinical Criteria but will Also Approve Funding for Off-Label Usage. PMID- 27202393 TI - Comparing How Single Arm Phase II Trial Data Can Support Approval of Oncologics by European Health Technology Assessment Bodies. PMID- 27202395 TI - Oncology Products in the Amnog Process - Learnings for a Successful Dossier Submission. PMID- 27202394 TI - The Cancer Drugs Fund: A Systematic Analysis of the Requirements For Inclusion on the English National List of Drugs for Priority Funding. PMID- 27202396 TI - Testing The Utility Of The Nhs's Systemic Anti-Cancer Therapy Data Set For Multi Indication Pricing. PMID- 27202397 TI - Media Coverage of the Nice First Draft Consultation Guidance for Trastuzumab Emantansine (Kadcyla) In Breast Cancer. PMID- 27202398 TI - Application of Threshold Value for Cost-Effectiveness in Recommendations Issued by Agency for Health Technology Assessment in Poland for Cancer Drug Technologies. PMID- 27202399 TI - Price Control Of Out-Patient Cancer Drugs In Bulgaria, 2010-2011: Reference Based Pricing And Public Tenders Verse Reference Based Pricing Only. PMID- 27202400 TI - Understanding Caregiver Burden in Colorectal Cancer: What Role Do Patient And Carer Factors Play? PMID- 27202401 TI - Investigating the use of Personalised Medicine in Cancer Trials - an Update. PMID- 27202402 TI - The Role Of Prior Breast Cancer Diagnosis In Articulating Expectations For Reconstructed Breast Appearance. PMID- 27202403 TI - Nice Restrictiveness Compared to the Market Authorization In Oncology And Non Oncology Reviews. PMID- 27202404 TI - Health Technology Assessments In Oncology: Crizotinib Case Study. PMID- 27202405 TI - Systematic Review of Economic Evaluations in Cancerology In Brazil Between 1980 And 2013. PMID- 27202406 TI - Impact of Health Care Reform on Drug Reimbursement Decision-Making In Taiwan. PMID- 27202407 TI - Applicability Of Eunethta Relative Effectiveness Assessment of Pazopanib For National Assessments. PMID- 27202408 TI - The Life and Death of the End of Life Treatment Appraisal Criteria in Nice Technology Appraisals? PMID- 27202409 TI - Expanded Data Sets For Hta Decision-Making In Oncology: Do They Help To Achieve Positive Appraisals? PMID- 27202410 TI - Human Epididymis Protein 4 Test. PMID- 27202411 TI - Meta-Analysis of Decision Impact and Net Decision Change in Adjuvant Chemotherapy Allocation in Early Stage Node-Negative, Estrogen Receptor-Positive Breast Cancer with a 21-Gene Assay. PMID- 27202412 TI - Ahmed Abouzid. PMID- 27202413 TI - Third Party Participation in Early Benefit Assessment of Cancer Drugs in Germany. PMID- 27202414 TI - Towards a Framework for Analysing Sustainability of Economic Value: The Case of a Short Stay Programme for Breast Cancer Surgery Care Five Years After Implementation. PMID- 27202416 TI - Anti-Cancer Treatments in Elderly (>=75 Years Old) Patients: A Retrospective Analysis. PMID- 27202415 TI - Systemic Treatment of Metachronous Metastases After Curative Treatment of Breast Cancer. PMID- 27202418 TI - Prescribing Pattern of Anti-Emetics for Prevention of Chemotherapy Induced Nausea & Vomiting-An Observation of Clinical Practice Versus Standard Guidelines. PMID- 27202417 TI - Current Guidance for Brca Mutation Testing in Ovarian Cancer Patients. PMID- 27202419 TI - Critical Assessment of Cost-Sharing Schemes Using a Simple Modeling Approach. PMID- 27202420 TI - New Reimbursement Schemes for Stratified Medicine in Oncology - A Systematic Review. PMID- 27202421 TI - Study on Clinical and Immunological Outcomes of Antiretroviral Therapy in Hiv Positive Adult Patients in a Community Care Hospital. PMID- 27202422 TI - Non-Inferiority of Once-Daily Cobicistat-Boosted Darunavir Versus Ritonavir Boosted Darunavir in Hiv-1-infected Adult Patients: An Adjusted Comparative Analysis of Pooled Phase 3 Data. PMID- 27202423 TI - Relationship Between Microbiological Eradication and Clinical Outcome with Antibiotic Treatment in Nosocomial Pneumonia, Complicated Urinary Tract Infection, and Complicated Intra-Abdominal Infection. PMID- 27202424 TI - Efficacy and Hospitalization Length of Stay of Single Dose Oritavancin Compared to 7-10 Days of Vancomycin in Patients with Acute Bacterial Skin and Skin Structure Infections in the Us and Eastern Europe. PMID- 27202425 TI - Retrospective Public Health Impact of a Quadrivalent Influenza Vaccine in the United States Over the Period 2000-2014. PMID- 27202426 TI - Fidaxomicin Therapy for Patients with Clostridium Difficile Infection: A Systematic Literature Review and Meta-Analysis. PMID- 27202427 TI - Mixed Treatment Comparisons to Compare Simeprevir with Boceprevir and Telaprevir in Combination with Peg-Interferon Alpha and Ribavirin (Pr) in Patients Infected with Genotype 1 Hepatitis C Virus (Hcv). PMID- 27202428 TI - Results of Comparative Study of Macrolide Group Antibiotics Consumption in Ukraine, Russia and Kazakhstan. PMID- 27202429 TI - Effects and Safety of Ceftriaxone Versus Levofloxacin in Treating Community Acquired Pneumonia: A Sysytematic Review. PMID- 27202430 TI - Impact of Hpv-Vaccination: Health Gains for Female Population In Italy. PMID- 27202431 TI - Ten Years Outcomes in a Cohort of Patients Started on Antiretroviral Treatment in an Urban Clinic in Sub-Saharan Africa. PMID- 27202432 TI - Meta-Regression on European Zoster Incidence. PMID- 27202433 TI - Disability-Adjusted Life Years (Dalys) as a Composite Measure to Express the Burden of Tick-Borne Encephalitis (Tbe) in Slovenia. PMID- 27202434 TI - Potential Epidemics of Drugs Resistant Bacteria in Poverty Stricken Countries Like Pakistan. PMID- 27202435 TI - Burden of Influenza B in 9 European Countries: A Literature Review. PMID- 27202436 TI - The Epidemiologic Burden of Hepatitis C Virus Infection in Egypt. PMID- 27202437 TI - Transitional Clinic Utilization and General Well Being of Ugandan Young Adults Living with HIV/AIDS. PMID- 27202438 TI - Budget Impact Analysis of 13-Valent Pneumococcal Vaccine in Adult Population with Comorbidities or Immunocompromised from the Public Payer Perspective In Brazil. PMID- 27202439 TI - Monitoring Antiretroviral Therapy in Uganda: Budget Impact Analysis of Two Strategies for Viral Load Monitoring Versus Immunologic Monitoring. PMID- 27202440 TI - Cost savings for the use of antibacterial sutures in spanish hospitals. Budget impact model. PMID- 27202441 TI - Predictors For Mortality Among Human Immunodeficiency Virus Infected Patients On Antiretroviral Therapy. PMID- 27202442 TI - Initial Inappropriate Antibiotic Therapy in Hospitalized Patients with Gram Negative Infections: Systematic Review And Meta-Analysis. PMID- 27202443 TI - Economic Impact of Dengue Episode: Multicenter Study Across Four Brazilian Regions. PMID- 27202444 TI - Triclosan Coated Antibacterial Suture: A Budget Impact Analysis from Italian Health Service Perspective. PMID- 27202445 TI - The Budget Impact of Using Fidaxomicin for Hospitalised Cdi Patients from the Danish Health Care Perspective. PMID- 27202446 TI - A comparative public health and budget impact analysis of pneumococcal vaccines. The french case. PMID- 27202447 TI - Costs Related to Pneumonia, Meningitis and Sepsis in Patients 50 Years and Older from the Private Health System Perspective in Brazil. PMID- 27202448 TI - Economic Evaluation of Vaccination Against Hav in High Risk Population. PMID- 27202450 TI - Fixed Dose Combinations of Nucleoside Reverse Transcriptase Inhibitor for Naive Patient with Hiv Infection in Russia: Cost Comparison Analysis. PMID- 27202449 TI - Treatment of Mrsa Pneumonia: Economical and Clinical Comparison of Linezolid Verse Vancomycin. PMID- 27202451 TI - Preliminary Assessment of the Cost of Treatment for Chronic Hepatitis C Virus Infections with Sofosbuvir and First Generation Antivirals Across Eight Countries. PMID- 27202452 TI - Cost Analysis for Management and Prevention of Hepatitis B Virus Reactivation. PMID- 27202453 TI - Median Hospitalization Cost and Length of Stay for Carbapenem-Resistant Verse Carbapenem-Sensitive Patients in a Tertiary Care Hospital in South India. PMID- 27202454 TI - Potential Risk-Sharing Agreements for Vaccines. PMID- 27202455 TI - The Cost-Effectiveness of Telaprevir Triple Therapy in Treatment of Naive Chronic Hepatitis C Patients In Turkey. PMID- 27202456 TI - The Cost-Effectiveness of Telaprevir Triple Therapy in Treatment-Experienced Chronic Hepatitis C Patients in Turkey. PMID- 27202457 TI - Economic Comparison of Empirical Versus Diagonstic-Driven Strategies for Immunocompromised Patients with Suspected Fungal Infection Results from a Chinese Payer Perspective. PMID- 27202458 TI - Epidemiology and Costs of Varicella and Herpes Zoster in Germany. PMID- 27202459 TI - The Burden of Clostridium Difficile (CDI) Infection in Hospitals, in Denmark, Finland, Norway And Sweden. PMID- 27202460 TI - Evaluating the Economic Burden and Health Care Utilizations of U. S. Veteran Patients Diagnosed with Chronic Hepatitis C. PMID- 27202461 TI - Burden of Disease Caused by Influenza in Germany - A Retrospective Claims Database Analysis. PMID- 27202462 TI - Cost Estimation of Hiv Infection in Greece: Data from an Infectious Diseases Unit. PMID- 27202463 TI - Hospitalization Costs For Community-Acquired Pneumonia In Elderly In The Netherlands. PMID- 27202464 TI - Direct and Indirect Cost of HCV-Related Diseases in Italy: An Incidence-Based Probabilistic Approach. PMID- 27202465 TI - Cost of Influenza and Acute Respiratory Infections Treatment in Ukraine. PMID- 27202466 TI - What are the Lifelong costs of Vaccinating one Individual? The French Case. PMID- 27202467 TI - Cost of Cirrhosis among Patients Diagnosed with Hepatitis C Virus in Turkey. PMID- 27202468 TI - Economic Burden and Complications of Hepatitis C Virus Patients With and Without Peginterferon and Ribavirin Treatment in Turkey. PMID- 27202469 TI - Cost-Benefit-Analysis of a Targeted Hospital Wide Pcr-Based Admission Screening for Mrsa in a German University Hospital - Consideration of a Six-Year Time Period. PMID- 27202470 TI - An Observational Propensity Score-Matched Study to Evaluate Cost-Effectiveness of a Real-Time Pcr-Based Assay in Patients with Suspected Sepsisk. PMID- 27202471 TI - Return on Investment of Preventively Vaccinating Health Care Workers Against Pertussis: A Dutch Case Study. PMID- 27202472 TI - Cost-Effectiveness of Fidaxomicin for the Treatment of Clostridium Difficile Infection (CDI) in Sweden. PMID- 27202473 TI - Protecting Productivity with Quadrivalent Inactivated Influenza Vaccine in the Uk. PMID- 27202474 TI - Cost-Effectiveness Analysis of Dolutegravir for HIV Patients in Slovenia. PMID- 27202475 TI - Estimating Overall Impact of Human Papillomavirus Vaccination on Cervical Cancer Burden in Spain and Portugal. PMID- 27202476 TI - Costs Per Successfully Treated Patient with Sofosbuvir in GT1 HCV. PMID- 27202477 TI - The Effect of Herd Immunity in Different Human Papillomavirus Vaccination Strategies: An Economic Evaluation of the Best Ii Study. PMID- 27202478 TI - Economic Evaluation of Fidaxomicin for the Treatment of Clostridium Difficile Infections (CDI) also Known as Clostridium Difficile-Associated Diarrhoea (CDAD) in Spain. PMID- 27202479 TI - Public Health and Economic Impact of Vaccinating Children with a Quadrivalent live Attenuated Influenza Vaccine in France Using a Dynamic Transmission Model. PMID- 27202480 TI - Costs and Effectiveness of Combination Therapy with Bedaquiline and other Anti Tuberculosis Drugs in Patients with Multi- and Extensively Drug-Resistant Tuberculosis in Germany. PMID- 27202481 TI - An Economic Model to Compare the Different Empiric and First/Second Line Treatment Regimens for Suspected Methicillin-Resistant Staphylococcus Aureus Nosocomial Pneumonia. PMID- 27202482 TI - How Do Decision Makers in Europe Value Other Economic Evaluation Tools Than Cost Effectiveness Analysis for Vaccines? PMID- 27202483 TI - Cost-Effectiveness Analysis of Different Therapeutic Regimens in Treatment of Community-Acquired Pneumonia in China. PMID- 27202484 TI - Cost-Effectiveness of Fidaxomicin Therapy for Clostridium Difficile Infection in Hungary. PMID- 27202485 TI - Cost-Effectiveness Analysis of Raltegravir in Hiv-Infected Treatment Naive Patients in Greece. PMID- 27202486 TI - Long-Term Outcomes of Ledipasvir/Sofosbuvir (LDV/ SOF) for the Treatment of Chronic Hepatitis C Infected (HCV) Genotype 1 Patients in the UK. PMID- 27202487 TI - Cost-Effectiveness and Long-Term Outcomes of Sovaldi (SOFOSBUVIR) for the Treatment of Chronic Hepatitis C Infected (HCV) Patients from a Swedish Societal Perspective. PMID- 27202488 TI - The Pan-Genotypic Costs-Effectiveness Of Sofosbuvir in Hepatitis C Virus. PMID- 27202489 TI - Cost-Effectiveness of Fecal Microbiota Transplant in Treating Clostridium Difficile Infection in Canada. PMID- 27202490 TI - The Importance of Sensitivity Analysis in Assessing Clinical and Economic Impact of National Immunization Programs: An Example of Slovenia. PMID- 27202491 TI - Allocating Vaccine Funds for Pneumococcal Vaccination of Infants and Older Adults: A Method for Strategic Evaluation in the Netherlands. PMID- 27202492 TI - Cost-Effectiveness of Human Papillomavirus Vaccination Programmes Parallel to Current Routine Vaccination of Young Teenage Girls. PMID- 27202493 TI - Cost-Effectiveness Analysis of a Shingles Vaccination Program to Prevent Herpes Zoster And Post- Herpetic Neuralgia in the Spanish Setting. PMID- 27202494 TI - Switching from an EFV-Based STR to a RPV-Based STR is Effective, Safe and Improves HIV Patients Health Status. PMID- 27202495 TI - A Cost-Effectiveness Evaluation for a New Therapy in HIV Treatment. PMID- 27202496 TI - Adding Boceprevir Yields Better Cost-Saving for Chronic Hepatitis C Genotype 1 Treatment in Thailand. PMID- 27202497 TI - A Systematic Review of Cost-Effectiveness Analysis of Cd4 Cell Count Verse Hiv Viral Load in Primarily Resource-Limited Setting. PMID- 27202498 TI - The Cost-Effectiveness of Different Scenarios of Detecting of TB Among HIV Infected People Depending on CD 4+ Count. PMID- 27202499 TI - Quadrivalent Influenza Vaccine in Hong Kong- a Cost-Effectiveness Analysis. PMID- 27202500 TI - Cost-Effectiveness Analysis of the Application of Ertapenem for the Treatment of Community-Acquired Complicated Intra-Abdominal Infections. PMID- 27202501 TI - Cost Effectiveness of Quadrivalent Influenza Vaccine Over Trivalent Vaccine in France. PMID- 27202503 TI - Xpert Mtb/Rif Assay for Rapid Diagnosis in Patients with Suspected Tuberculosis in Hong Kong - a Cost-Effectiveness Analysis. PMID- 27202502 TI - Cost-Effectiveness of Dolutegravir, a New Generation Integrase Inhibitor, in Hiv 1 Treatment Experienced Patients in France. PMID- 27202504 TI - The Cost-Effectiveness Analysis for Hiv Treatment Alternatives in Turkey. PMID- 27202505 TI - Cea of Introducing Rotavirus Vaccine in Libya. PMID- 27202506 TI - Cost-Utility Analysis of Dolutegravir Compared to Raltegravir in Treatment Naive and Treatment Experienced Patients in Slovak Settings. PMID- 27202507 TI - Health Economic Model for Novel in Vitro Diagnostic Kit for Infective Endocarditis. PMID- 27202508 TI - Cost-Effectiveness of Quadrivalent Versus Trivalent Influenza Vaccine in the United States. PMID- 27202509 TI - Cost-Utility Analysis of Simeprevir With Peginterferon + Ribavirin (SMV/PR) in the Management of Genotype 1 (G1) and 4 (G4) Hepatitis C Virus (HCV) Infection; from the Perspective of the Uk National Health Service (NHS). PMID- 27202510 TI - What Drives Unemployment of HIV-Infected Patients in Germany? PMID- 27202511 TI - Indirect Costs Among Patients with Hepatitis C Virus. PMID- 27202512 TI - Resource Utilisation in a Complex Treatment Regimen for Hepatitis C. PMID- 27202514 TI - Predicting the Impact of Adverse Events and Treatment Duration on Medical Resource Utilisation Related Costs in Hepatitis C Genotype 1 Treatment-Naive Patients Receiving Antiviral Therapy. PMID- 27202513 TI - Resource use and Costs for Managing HCV Genotype 1 Patients in Colombia from the Payers Perspective. PMID- 27202515 TI - A macro Economic Analysis of 65 Year-Old 'Rendez-vous Vaccinal 'in France: What is the Return on Investment? PMID- 27202517 TI - Development of a Survey to Quantify Parents' Priorities for Vaccinating Children Against Rotavirus. PMID- 27202516 TI - Confirmation of the Factor Structure of the Proqol-HIV Questionnaire to Assess Health-Related Quality of Life in PLWHA. PMID- 27202518 TI - Hand Hygiene Compliance or the Influencing Factors of Efficiency in the Scope of Students. PMID- 27202520 TI - What explains willingness to pay for avoiding morbidity risk due to malaria? Results from a global meta analysis. PMID- 27202519 TI - Persistence to Treatment of Chronic Hepatitis B Virus (Hbv) Infection: A Study Based on the French Ims Lifelink Treatment Dynamics (LTD) Database. PMID- 27202522 TI - Satisfaction of Hiv Patients with Pharmacy Services in South Eastern Nigerian Hospitals. PMID- 27202521 TI - Impact of Simeprevir Versus Telaprevir Triple Therapy for Chronic Hcv Infection on Patient-Reported Outcomes in Prior Non-Responders to Peginterferon/Ribavirin Results from the Phase Iii Attain Study. PMID- 27202523 TI - Knowledge of HIV Status of Adolescents and Young Adults Attending an Adolescent HIV Clinic in Accra, Ghana. PMID- 27202524 TI - Implementation of Technologies Based on the Evidence-Based Medicine and Hta in the Management of Hepatitis C. PMID- 27202525 TI - Prescription Practices for Uncomplicated Malaria at two Public Health Facilities in Nigeria; A Descriptive, Comparative Study. PMID- 27202526 TI - Modelling the Relationship between Sustained Virologic Response and Treatment Uptake Rates on Future Prevalence and Incidence of Hepatitis C in the UK. PMID- 27202527 TI - Cost-Effectiveness Analysis of Protease Inhibitor Monotherapy Verse Ongoing Triple-Therapy in the Long-Term Management of HIV Patients. PMID- 27202528 TI - Cost of Adverse Drug Reactions (ADR) with Protease Inhibitors in the Treatment of Hepatitis C in the Health System of Extremadura (SES). PMID- 27202529 TI - Primary care physicians in an interferon-free world: could safer, more efective oral hepatitis c therapies lead to improved outcomes through education and pcp prescribed treatment? PMID- 27202530 TI - Coverage or Efficacy: Which Factor is the Most Influential for Reducing Varicella with Routine Childhood Vaccination in Italy? PMID- 27202532 TI - Coping with methicillin resistant staphylococcus aureus (MRSA) in german rehabilitation centers - are the incentives appropriate? PMID- 27202531 TI - Early Switch/Early Discharge Opportunities for Hospitalized Patients with Methicillin-Resistant Staphylococcus Aureus Complicated Skin And Soft Tissue Infections: Proof Of Concept in the United Arab Emirates. PMID- 27202533 TI - Herpes Zoster-Related Health Care Resource Utilization in Cancer Patients in 5 European Countries. PMID- 27202534 TI - Use of Hospital Services by HIV Patients, 2012. PMID- 27202536 TI - Estimating the Direct Medical Cost, Length of Stay and Impact of Reimbursement Change on Health Care Associated Infections. PMID- 27202535 TI - The Impact of Influenza like Illness (ILI) in Children on Working Adults. PMID- 27202537 TI - Evaluation of the Effectiveness of Implementing an Antimicrobial Stewardship Program in a Medical Center in Taiwan. PMID- 27202538 TI - The Study on the Prescribing Pattern of Acinetobacter Infection in a Tertiary Care Hospital. PMID- 27202539 TI - Pediatrician's Perspective On Pneumococcal Conjugate Vaccines In India: An Exploratory Study. PMID- 27202540 TI - Analyses on Temporal and Spatial Clustering and Changing Trend of HCV in Mainland of China. PMID- 27202541 TI - Corrective Estimation of New Cases of Hepatitis C Infections in China Between 2005 and 2013. PMID- 27202542 TI - Are antibiotic Policies and Reimbursement Decisions Aligned? PMID- 27202543 TI - Managed-Entry Agreements: Possible Options for Vaccines? PMID- 27202544 TI - Impact of Glp-1RA on Heart Rate, Blood Pressure and Hypertension Among Type 2 Diabetes: A Systematic Review and Network Meta-Analysis. PMID- 27202545 TI - Study On The Direct Medical Cost of Malignant Neoplasms Inpatients With Urban Basic Health Insurance Scheme in China. PMID- 27202546 TI - Treatment Strategies For Stage Ib Cervical Cancer: A Cost-Effectiveness Analysis. PMID- 27202547 TI - Cost-Effectiveness Analysis Of Computed Tomographic Colonography Versus Double Contrast Barium Enema For Investigation Of Patients With Symptoms Of Colorectal Cancer: Economic Evaluation Alongside The Siggar Trial. PMID- 27202548 TI - Budget Impact Analysis Of Crizotinib Treatment In Alk+ Non-Small-Cell Lung Cancer Patients In Thailand. PMID- 27202549 TI - Treatments Prior to and Post Percutaneous Coronary Intervention (PCI) in China. PMID- 27202550 TI - Example of Analysis Utilizing Real World Data: Medical Cost Reduction of Combination Drugs. PMID- 27202551 TI - Clinical Characteristics Among Hypertension Patients with Dislipidemia In Shanghai, China. PMID- 27202552 TI - Treatment Profile And Insulin Dose as a Factor Impacting Glycaemia Control Among Premix Insulin Users with T2DM in China. PMID- 27202553 TI - Efficacy and Safety of Human Insulin Versus Animal Insulin Among Patients with Diabetes in China: A Meta-Analysis. PMID- 27202554 TI - Trends of Hypnotic Medication Use in A 2000-Bed Medical Center in Taiwan. PMID- 27202555 TI - Statin Medication Use and the Development of Proliferative Diabetic Retinopathy Among Patients with Type 2 Diabetes, Hypertension, and Hyperlipidemia. PMID- 27202556 TI - Clinical Outcomes Associated with the Use of Guideline Recommended Care in Patients Post Discharge from Chronic Obstructive Pulmonary Disease (COPD). PMID- 27202557 TI - Qualitative Assessment of the Quality of Pharmaceutical Care Services in the Province of Khyber Pakhtunkhwa, Pakistan: Hospital Pharmacists' Views. PMID- 27202558 TI - Had the Individual Medical Burden of Basic Health Insurance Participants Really Been Alleviated in 2009-2012? PMID- 27202559 TI - Medication Adherence as a Value Message: A Rarity In Evaluation Assessments Submitted to Major Hta Bodies. PMID- 27202560 TI - Current Impact of Dementia on the Caregiver in China. PMID- 27202562 TI - Comparison of Oral Versus Intravenous Nsaids for the Treatment of Patent Ductus Arteriosus in Preterm and/or Low Birth Weigh Infants: A Systematic Review and Meta-Analysis. PMID- 27202561 TI - Clinical and Economic Outcomes of Memantine Used in Moderate or Severe Dementia Patients in China: Results from a Health Economic Model. PMID- 27202563 TI - Efficacy and Safety of Paliperidone Palmitate in the Treatment of Schizophrenia: A Meta-Analysis. PMID- 27202564 TI - Factors Associated with Relocating to Nursing Homes Among Community-Dwelling Older Persons with Dementia. PMID- 27202565 TI - Management of Ischaemic Stroke Patients Enrolled in the Japan Stroke Databank (JSD). PMID- 27202566 TI - Economic Evaluation of Change in Reimbursement Criteria for Lipid-Lowering Drugs in Taiwan. PMID- 27202567 TI - Does the Current Recommended Target LDL Goal Improve Survival for Acute Coronary Syndrome Patients in Hong Kong? PMID- 27202568 TI - Anticipated Price Disclosure: Impact on Funding Decisions in Australia. PMID- 27202569 TI - Impact Evaluation of Provider Payment Reform Under the New Rural Cooperative Medical Scheme in Gansu Province, China. PMID- 27202570 TI - Health Care Utilization and Cost Comparison Between Adherent Hypertension Patients Treated by Single Exforge HCT and Amlodipine/Valsartan/Hydrochlorothiazide Free Combination. PMID- 27202571 TI - Why Does Anti-Infective Drug Expenditure Increase?-a Decomposition Analysis on China Data. PMID- 27202573 TI - Effect of Vaccination Age on Cost-Effectiveness of Human Papillomavirus Vaccination Against Cervical Cancer in China. PMID- 27202572 TI - Comparative Safety and Efficacy of Focused Ultrasound for Cervical Ectopy: A Meta Analyses with 16180 Patients. PMID- 27202574 TI - Cost-Effectiveness Analysis of Caspofungin Compared to Conventional Amphotericin B (C-AMB) for Empirical Antifungal Therapy in Febrile Neutropenic Patients in Thailand. PMID- 27202575 TI - Impact of Maternal Education on Child Immunization Propensity in China. PMID- 27202576 TI - Asthma Guideline Knowledge, Adherence and Cost of Treating Asthma at Emergency Department. PMID- 27202577 TI - Cost-Utility of Bevacizumab with PC Regimen in Non-Small Cell Lung Cancer Treatment. PMID- 27202579 TI - Resource Utilization Pattern And Cost Of Tuberculosis Treatment In Penang, Malaysia. PMID- 27202578 TI - Cost-Effectiveness of Thrombolysis Within 4.5 Hours of Acute Ischemic Stroke in China. PMID- 27202580 TI - Comparison of the Preference-Based EQ-5D and SF-6D Health Indices in Multiethnic Asian Patients with End-Stage Renal Disease (ESRD). PMID- 27202581 TI - An Analysis of New Health Technologies and Reimbursement Pricing Structures in Taiwan. PMID- 27202582 TI - Acute Respiratory Distress Syndrome: Treatment Pattern and Outcome Analysis. PMID- 27202583 TI - Awarness and Prevention of Chronic Diseases in Japan. PMID- 27202584 TI - Cost-Utility Analysis of Varenicline Versus Existing Smoking Cessation Strategies in Korea. PMID- 27202585 TI - Histoculture Drug Response Assay in Colorectal Cancer. PMID- 27202587 TI - Health Economics Methodologies Involving Parkinson's Disease Treatment in China. PMID- 27202588 TI - Drugs in Constraint Countries of Sub Saharan Africa. PMID- 27202586 TI - Role of Corticosteroids Use in Ards: Comparison of Systematic Review and Meta Analysis. PMID- 27202589 TI - Is Chinese Syndrome Necessary in the Effectiveness Evaluation of Chinese Herbal Formulas? PMID- 27202590 TI - A Novel Broadly Applicable Risk Score for Predicting Mortality of Patients with Circulatory System Diseases within Hospitalization Duration. PMID- 27202591 TI - Disease Burden of Multiple Myeloma in China. PMID- 27202592 TI - Health Care use and Oral Medication Patterns for Type 2 Diabetes Patiets in China:The Role of Traditional Chinese Medicines. PMID- 27202593 TI - Assessment of Need, Development and Implementation of Supportive Management Database for the Treatment of Poisoning Cases in a Tertiary Care Hospital. PMID- 27202594 TI - Evidence for Validity of a National Physician and Patient-Reported Survey in China and United Kingdom: The Disease Specific Programme. PMID- 27202595 TI - Real World Evidence in Mainland China: Experience with the Use of Health Care Claims Data. PMID- 27202596 TI - Managing Congenital and Pediatric Cardiac Surgery Data Base: The Impact on Clincial Practice and Quality of Care. PMID- 27202597 TI - Health Care Databases Applied to Antidepressants Use in Asia-Pacific. PMID- 27202598 TI - Development of a Longitudinal National Football League Injury and Injury Impacts (L-NFL-III) Database. PMID- 27202599 TI - Build Model with Asia Pacific Region in Mind: Modeling INR Control in a Cost Effectiveness Model for Stroke Prevention in Atrial Fibrillation Patients. PMID- 27202600 TI - Strategies To Overcome Hurdles In Hta Appraisals Amid Limitations Resulting From Single-Arm Trial Data. PMID- 27202602 TI - Upfront Overall Survival Modelling in Comparison to Real World Data: Lenalidomide for the Treatment of Multiple Myeloma Patients in South Korea. PMID- 27202601 TI - Comparing the Event Prediction Capability of the Ukpds68 and Hong Kong Diabetes Risk Equations within A Type 2 Diabetes Simulation Model. PMID- 27202603 TI - Using Transmission Dynamic Model to Determine Vaccination Coverage Rate Based on Economic Burden of Infectious Disease: An Example of Pneumococcus Vaccine. PMID- 27202604 TI - Single-ARM Studies to Support Drug Reimbursement in Australia. PMID- 27202605 TI - The Reliability and Validity of the Chinese Version of the Eight-Item Morisky Medication Adherence Scale. PMID- 27202606 TI - A Single Model for Determining Socioeconomic Status in Health Studies; A Crucial Step to Make the Results More Comparable. PMID- 27202607 TI - Construct Validity of SF-6D Health State Utility Values in an Employed Population. PMID- 27202608 TI - Economic evaluation of diabetes care interventions in china: a system science approach. PMID- 27202609 TI - HBA1C Control Predictive Validity of Four Self-Reported Measures of Antidiabetes Medication Adherence. PMID- 27202610 TI - Sqaros - Standardized Questionnaire to Assess the Reliability of Observational Studies. PMID- 27202611 TI - Assessing Statistical Methods for Causal Inference in Observational Data. PMID- 27202612 TI - A Survey of Knowledge and Attitude of Menopause Among Post-Menopausal Women in Pakistan. PMID- 27202613 TI - Validation of Russian Version of Health Utility Index Questionnare in Children with Cystic Fibrosis. PMID- 27202614 TI - A Comparison of Three Language Versions of the EQ-5D-5L Dimension Scales in Singapore. PMID- 27202615 TI - The Decision Criteria for Assessing Cost-Effectiveness of a Health Care Technology Under Budget Constraint. PMID- 27202616 TI - Use of the Grace Checklist for Rating the Quality of Observational Comparative Effectiveness Research. PMID- 27202617 TI - How Well the Pragmatic Randomized Controls in Joint Replacement Field: Results from Precis, Consort and Iom Tools' Assessment. PMID- 27202618 TI - Methods for Evaluation of Medical Devices. PMID- 27202619 TI - WX-III-287-19 A Possible Thromboxane Antagonist in Bovine Coronary Arteries. PMID- 27202620 TI - Ethical Consideration on Methods of Health Research. PMID- 27202621 TI - Bevacizumab for Metastatic Colorectal Cancer: A Literature Review on Meta Analyses and Cost-Effectiveness Analyses. PMID- 27202622 TI - A Systematic Literature Review on Risk Factors for Cervical Cancer in Chinese Population. PMID- 27202623 TI - Sequential Combination of Chemotherapy With Egfr-Tki As The First-Line Treatment for Unselected Patients With Advanced Non-Small Cell Lung Cancer: Systematic Review of Randomized Controlled Trials. PMID- 27202624 TI - Prostate Cancer Overall Survival: Multilevel Analysis of A Population-Based Cancer Registry Data. PMID- 27202625 TI - Prevalence of Febrile Neutropenia in Breast Cancer Patients Received Adjuvant Paclitaxel Treatment. PMID- 27202626 TI - The Importance and Use of Drug Utilization Review and Pharmacoeconomics. PMID- 27202627 TI - Economic Burden of Febrile Neutropenia in Solid Tumor and Lymphoma Patients: An Observational Study in Singapore. PMID- 27202628 TI - Hospital Costs Associated with Platinum-Based Doublets in the First-Line Setting for Advanced Non-Squamous Non-Small Cell Lung Cancer in China: A Retrospective Cohort Study. PMID- 27202629 TI - Cost-Effectiveness Analysis of the Original Drug Arglabin. PMID- 27202630 TI - HEALTH CARE RESOURCE USE AMONG ADVANCED GASTRIC CANCER PATIENTS IN TAIWAN AND SOUTH KOREA. PMID- 27202631 TI - Budget Impact Model of Sunitinib as First Line Treatment of Metastatic Renal Cell Carcinoma in China. PMID- 27202632 TI - Annual Health Insurance Cost of Breast Cancer Treatment in Hungary. PMID- 27202633 TI - Analysing The Effects of a Disinvestment Decision in Breast Cancer Screening Programmes in Asia-Pacific Countries: A Modelling Approach. PMID- 27202634 TI - Cost-Effectiveness Analysis of 1-Year Adjuvant Trastuzumab Therapy of Early-Stage Her2-Positive Breast Cancer. PMID- 27202635 TI - COST EFFECTIVENESS ANALYSIS OF ANTIDEPRESSANTS ON BREAST CANCER PATIENTS: A MARKOV MODELING STUDY. PMID- 27202636 TI - Cost-Effectiveness Of Para-Aortic Lymphadenectomy Before Chemoradiotherapy in Locally Advanced Cervical Cancer. PMID- 27202637 TI - Treatment Costs for Breast Cancer in Japan: Large Claim Database Analysis. PMID- 27202638 TI - Cost-Effectiveness of Lenalidomide-Plus-Dexamethasone in Multiple Myeloma Patients Who Have Received at Least One Prior Therapy: A South Korean Perspective. PMID- 27202642 TI - Economic Evaluation of Primary Prophylaxis Using Filgrastim Versus Pegfilgrastim in Patients With Solid Tumor Cancer: A Systematic Literature Review. PMID- 27202643 TI - Cost-Utility Analysis of First-Line Regimen Between Cisplatin Plus Pemetrexed and Carboplatin Plus Paclitaxel In Advanced Non-Squamous Non-Small-Cell Lung Cancer in Thailand. PMID- 27202646 TI - Measuring the Trend of Use of Targeted Therapy and Economic Evaluation of Gefitinib for Advanced Non-Small Cell Lung Cancer (Nsclc) in Singapore. PMID- 27202645 TI - Impact of Vaccination: Health Impact and Cost-Effectiveness to Make Informed Policy Decision on the Introduction of Human Papillomavirus (Hpv) Vaccine to the National Immunization Program (Nip) in Thailand. PMID- 27202647 TI - A Cost-Utility Analysis of Cervical Cancer Screening and Human Papilloma Virus Vaccination In the Philippines. PMID- 27202649 TI - Health-Related Quality of Life In Patients With Cervical Cancer in Indonesia. PMID- 27202639 TI - Cost-Effectiveness Of First-Line Therapy For Advanced Non-Small Cell Lung Cancer (Nsclc). PMID- 27202641 TI - COST-EFFECTIVENESS OF POST-THERAPY PET AND TELEPHONE INTERVIEW IN THE CLINICAL FOLLOW-UP OF PATIENTS TREATED WITH LOCALLY ADVANCED CERVICAL CANCER. PMID- 27202640 TI - Health Economic Evaluation of Guangdong Rural Tertiary Breast Cancer Screening and Diagnosis System. PMID- 27202650 TI - Mapping the Functional Assessment of Cancer Therapy - Breast (Fact-B) to the 5 Level Euroqol Group's 5-Dimention Questionnnaire (Eq-5d) Index in a Multi-Ethnic Asian Breast Cancer Patients. PMID- 27202644 TI - Abraxane Versus Taxol For Patients with Advanced Breast Cancer: A Prospective Time and Motion Analysis from a Chinese Health Care Perspective. PMID- 27202648 TI - Attitude Assessment of the Human Papilloma Virus (Hpv) in Hungary. PMID- 27202651 TI - Quality of Life Among Patients with Esophageal/Cardiac Precursor Lesion or Cancer: A One-Year Prospective Survey. PMID- 27202653 TI - Breast Cancer Awareness Survey. PMID- 27202655 TI - Change in Percentage of Left Ventricular Ejection Fraction in Breast Cancer Patients Received Trastuzumab Treatment. PMID- 27202654 TI - Comparative Analysis of Pain Intensity in Hospice Care at Home and in Hospitals. PMID- 27202652 TI - Understanding the Rationale for Responses to a Time-Trade-Off Assessment and Willingness-To-Pay in Lung Cancer in Thailand. PMID- 27202656 TI - The Differences Between Cancer Drug Approvals in Japan and the USA. PMID- 27202657 TI - Economic Impact of Genetic Diagnostic Test For Breast Cancer - Health Technology Assessment in Slovak Health Care Environment. PMID- 27202658 TI - Insurance Coverage Policies for Companion Diagnostics in Breast Cancer. PMID- 27202659 TI - In Vitro Drug Release and Ex Vivo Permeation Study of Prepared Mouth Dissolving Tablets of Fluconazole Through Porcine Buccal Mucosa. PMID- 27202660 TI - CANCER TREATMENT IN CHINA: HOW ARE POLICY AND PRACTICE IN TIER 1 VERSUS TIER 2/3 CITIES IMPACTING PATIENT ACCESS TO HIGH-COST THERAPIES. PMID- 27202661 TI - The Incidence, Prevalence, and Survival of Malignant Melanoma in Taiwan. PMID- 27202662 TI - Coverage Decision Framework in Asia Pacific: A Case Study of Targeted Cancer Medicines in the Treatment of Breast Cancer. PMID- 27202663 TI - Time to Reimbursement for Oncology Agents from EMA Marketing Authorization to AIFA Approval AS "C(NN)" Class versus. AIFA Approval AS "A" or "H" Class. PMID- 27202664 TI - HOW SINGLE ARM PHASE II DATA CAN SUPPORT REIMBURSEMENT FOR ONCOLOGICS IN AUSTRALIA. PMID- 27202665 TI - Quality Control of the Hungarian Nationwide Mammography Screening Programme. PMID- 27202666 TI - Incretin Therapy and Risk of Pancreatitis in Type 2 Diabetes Mellitus: Systematic Review of Randomized and Non-Randomized Studies. PMID- 27202667 TI - Evaluating The Effects Of Anti-Thyroid Drugs And Thyroidectomy In Patients Receiving Radioactive Iodine Therapy For Graves' Hyperthyroidism - A Retrospective Study From A University Teaching Hospital In South West, Nigeria. PMID- 27202668 TI - Premixed Insulin Lispro Versus Insulin Glargine In Type 2 Diabetes: A Meta Analysis. PMID- 27202669 TI - Efficacy Of Add - On Vildagliptin Therapy To Metformin For Type Ii Diabetes Mellitus Patients In South Indian Resource Limited Settings - Pilot Study. PMID- 27202670 TI - Diagnostic Tests Of Blood Glucose: A Systematic Review. PMID- 27202671 TI - Effectiveness Of Herbotrim And Muniprabha In The Management Of Hypothyrodism. PMID- 27202674 TI - Studies On Clinical Effectiveness Of Combined Classical Ayurvedic Formulations In Type 2 Diabetes Mellitus. PMID- 27202675 TI - Impact Of Ethnicity On The Efficacy And Safety Outcomes Of Anti-Diabetes Drugs - Case Study Of Liraglutide In Asian And Non-Asian Populations. PMID- 27202673 TI - Hydroxyethyl Starch And Hospitalized Mortality In Icu Patients With Diabetes: Database Study From A Chinese Tertiary Hospital. PMID- 27202672 TI - Design & Methods For Study Of Prevalence, Risk Factors And Economic Burden Of Insulin Injection-Related Lipohypertrophy In China. PMID- 27202676 TI - The Long-Term Outcomes Of Bariatric Surgery On Patients With Type 2 Diabetes Mellitus: A Systematic Review And Meta-Analyses. PMID- 27202677 TI - The Impact Of Diabetes On Mortality In Inpatients From Medical Department Of A Chinese Tertiary Hospital. PMID- 27202678 TI - Economic Burden Of Type 2 Diabetes Mellitus For Costa Rica. PMID- 27202679 TI - Budget Impact Analysis Of Biphasic Insulin Aspart In The Treatment Of Type 2 Diabetes Mellitus In Malaysia: A Public Payer Perspective. PMID- 27202680 TI - Budget Impact Analysis Of U100 Insulin In Egyptian Diabetic Patients. PMID- 27202681 TI - Budget Impact Analysis Of Wider Adoption Of Biphasic Insulin Aspart (Biasp) In The Treatment Of Type 2 Diabetes Mellitus (T2dm): A Perspective Of Patients Treated By Public Providers In Singapore. PMID- 27202683 TI - Medical Expenditure For People With Diabetes In Urban Employee Basic Medical Insurance For Hebei Provincial Institutes. PMID- 27202682 TI - Health Care Utilizations And Costs Of Insulin Patient-Driven Titration Versus Physician-Driven Titration: Evidence Based On A Clinical Trial Of Biphasic Insulin Aspart 30 Twice Daily In People With Type 2 Diabetes In China. PMID- 27202684 TI - Evaluating The Long-Term Cost-Effectiveness Of Liraglutide 1.2 Mg And Exenatide In Patients With Type 2 Diabetes Mellitus. PMID- 27202685 TI - Economic Implications Of Chronic Renal Disease With And Without Co-Morbid Diabetes In China, Post-2005. PMID- 27202686 TI - Example Of Analysis Utilizing Real World Data: Medical Cost Reduction By Advising Untreated-Diabetes Patients To Visit Doctors. PMID- 27202687 TI - Clinical Efficacy And Costs Of Insulin Analogue Compared To Human Insulin In Patients With Diabetes: Results From A Tertiary Hospital In Beijing. PMID- 27202688 TI - Pharmacoeconomics Evaluation Of Clinical Pharmacy Service For Diabetic Inpatients. PMID- 27202690 TI - Cost Minimization Analysis Of Clinical Option Scenarios For Metformin And Acarbose In Treatment Of Type 2 Diabetes: Based On Direct And Indirect Treatment Comparison Results. PMID- 27202689 TI - Pharmacoeconomic Evaluation Study On Preoperative Treatment Of Acromegaly With Somatostatin Analogues In Shanghai. PMID- 27202691 TI - Economic Evaluation Of Insulin Analogs Versus Human Insulin For Diabetes: A Systematic Review. PMID- 27202692 TI - Long-Term Cost-Effectiveness Of Biphasic Human Insulin 30 In People With Type 2 Diabetes With Inadequate Glycaemic Control On Oral Antidiabetic Drugs In China. PMID- 27202693 TI - Cost Utility Of Diabetes Drugs Using Hba1c As A Direct Predictor For Quality Of Life, Diabetes Complications And Mortality. PMID- 27202694 TI - Cost Minimization Analysis Of U100 Insulin And U40 Insulin In Egyptian Diabetic Patients. PMID- 27202695 TI - Demographics And Health Outcomes Associated With Adherence And Non-Adherence Among Type2 Diabetics In China. PMID- 27202696 TI - Anti-Diabetic Drug Utilization And Dynamic Trends In A Tertiary Hospital In Beijing (2008-2012). PMID- 27202697 TI - A Prospective, Cross-Sectional Study On Cost And Adherence Of Antidiabetic Prescriptions At A Tertiary Care Teaching Hospital In South India. PMID- 27202698 TI - Medication Counseling Beyond Instituitional: Impact Of Pharmacist-Led Home Medication Review In Type 2 Diabetes Patients. PMID- 27202699 TI - Does diabetes have an impact on health-state utility? A study of asians in singapore. PMID- 27202700 TI - Assessment Of Disease State Knowledge In Diabetic Patients Of Quetta City, Pakistan. PMID- 27202701 TI - Patient-Reported Medical Expenditures For Insulin-Treated Diabetes Patients In Eastern, Central And Western Regions Of China. PMID- 27202702 TI - The Impact Of Drug Price Control Policy For Diabetes Medication: A Longitudinal Analysis In Taiwan. PMID- 27202703 TI - The Expanding Role Of The Patient Voice In Medical Decision Making In Asia. PMID- 27202704 TI - Assessment Of Diabetes Knowledge In Healthy Population Of Quetta City, Pakistan. PMID- 27202705 TI - Assessment Of Knowledge Regarding Diabetes: A Comparative Analysis Of Diabetes Patients And Healthy Population Of Quetta City, Pakistan. PMID- 27202706 TI - Physicians As Double Agents In A Universal Health Care System: Evidence From Generic Pharmaceutical Adoption In Taiwan. PMID- 27202707 TI - Loyalty To A Pharmacy Is Associated With A Better Quality Of Antidiabetes Drug Use. PMID- 27202708 TI - Content Analysis And Effectiveness Of Interventions To Enhance Oral Antidiabetic Drug (Oad) Adherence In Adults With Type 2 Diabetes: A Systematic Review And Meta Analysis. PMID- 27202709 TI - Decomposing Growth Of Diabetes Drug Expenditure In Korea. PMID- 27202710 TI - ESTIMATED ECONOMIC BURDEN OF INSULIN INJECTION-RELATED LIPOHYPERTROPHY IN CHINESE PATIENTS WITH DIABETES. PMID- 27202711 TI - Economic Evaluation of Viral Load Test (VLT) in Response Guided Treatment (RGT) for Chronic Hepatitis C (CHC). PMID- 27202712 TI - Chewing a Gum: Effect on Saliuvation, Passing out of Flatus, Bowel Movement and Gastric Motility Among Filipino Elderly. PMID- 27202713 TI - TC-325 in the Management of Upper and Lower GI Bleeding: A Two-Year Experience at a Single Institution. PMID- 27202714 TI - Pregnancy Outcomes in Women with Inflammatory Bowel Syndrome Following Exposure to Thiopurines and Anti-Tumor Necrosis Factor Drugs: A Meta-Analysis and Systematic Review. PMID- 27202715 TI - Application Of Medicines Scoring System (Medss) : Potential Savings Through Drug Formulary Review Of Sulphonylureas. PMID- 27202716 TI - Pharmacological Regimens for Eradication of Helicobacter Pylori: An Overview of Systematic Reviews and Network Meta-Analysis. PMID- 27202717 TI - Drug Utilization Review of Acid Suppressants (Durable) - an Audit to Assess the Utilization of Proton Pump Inhibitors and Histamine H2-Receptor Antagonists in Canadian Hospitals. PMID- 27202718 TI - Adverse Drug Events: How Information Technology will Meet the Challenges of Pharmacovigilance. PMID- 27202719 TI - Modeling to Predict Severe Maternal Morbidity Based on 33993 Deliveries of Registered Study in China. PMID- 27202720 TI - The Efficacy of Oximes in Acute Organophosphorus Poisoning; An Updated Systematic Review and Meta-Analysis. PMID- 27202721 TI - Effect of Vitamin E on the Vaginal Atrophy of Postmenopausal Women. PMID- 27202722 TI - Efficacy of Atropine Alone and with Glycopyrrolate Combination in Organophosphate Poisoning. PMID- 27202723 TI - Disease Burden of Unintended Pregnancy in China. PMID- 27202724 TI - Using Hormonal Contraception Reduce Unintended Pregnancy in China. PMID- 27202725 TI - An Update of Cost-Effectiveness of Rotavirus Vaccination in Indonesia: Taking a Birth-Dose Vaccination Strategy into Account. PMID- 27202726 TI - The Effectiveness of First Trimester Combined Screening on Reducing the Rate of Invasive Genetic Procedures in a City Based Population of Hungary 2010-2013. PMID- 27202728 TI - The Pharmacoeconomics Review of 7-Valent Pneumococcal Conjugate Vaccination in Asian-Pacific Region. PMID- 27202727 TI - Burden of Disease in Asian Countries and the use of Disability-Adjusted Life Years and Quality-Adjusted Life-Years. PMID- 27202729 TI - Joint Modeling of Primary and Secondary Non-Adherence Outcomes. PMID- 27202730 TI - Partial Reimbursement of Antiviral Agents for HBV: Impact on Antiviral Utilization and Compliance. PMID- 27202731 TI - A Qualitative Assessment of Doctors Perception Towards the Quality of Pharmaceutical Care Services in Khyber Pakhtunkhwa, Pakistan. PMID- 27202732 TI - Reference Value of Blood Serum Alkaline Phosphatase in Mongolian Adult. PMID- 27202733 TI - Assessment of Utilities in Japan: Data Availability and Methodology. PMID- 27202734 TI - Assessing Factors Associated with Youth Substance Abuse in the us Using a Structural Equation Model. PMID- 27202735 TI - The Study of Satisfaction and Reasons for Acupuncture Therapy at Sirindhorn National Medical Rehabilitation Centre. PMID- 27202736 TI - The Valuation of EQ-5D-5L Health States in Korea. PMID- 27202737 TI - Valuing Health in the Uae: An Investigation of the Feasibility and Cultural Appropriateness of Using the TTO and DCE Methods to Generate Health State Values. PMID- 27202738 TI - Impact of Demographics on Health Preferences in China: An Exploratory Analysis of China EQ-5D-5L Valuation Study. PMID- 27202739 TI - What Really Matters? A Multi-View Perspective of One Patient's Hospital Experience. PMID- 27202740 TI - Construct a Cpoe Decision Supporting and Monitoring System to Decrease Pims Used in Hospitalized Elderly Patients. PMID- 27202741 TI - Spontaneous Reporting of Adverse Drug Reactions in Geriatric Patients in India. PMID- 27202742 TI - The Patient Voice in China: Status Quaestionis. PMID- 27202743 TI - Will Nurses Have Better Outcomes than Non-Medical Working Women when Hospitalized for Female Genital Diseases? PMID- 27202744 TI - Health Related Quality of Life and Medication use Among Young College Students During Menstrual Cycle. PMID- 27202745 TI - Assessment of KAP Among Hospital Pharmacists. PMID- 27202746 TI - An Ecological Analysis on National Trends and Correlation Between Public Funding for Pneumococcal Vaccination and Pneumonia Disease Burden in the Japanese Elderly Population, 2005-2012. PMID- 27202747 TI - Comparative Study On Health Related Quality Of Life Of Farmers And Workers. PMID- 27202748 TI - Community Pharmacists Attitude and Perceived Need Towards the Provision of Pharmaceutical Care Services: A Qualitative Approach. PMID- 27202749 TI - Nurses' Perception Towards the Benefits of Pharmaceutical Care Services in Tertiary Health Care Settings Pakistan: A Qualitative Insight. PMID- 27202750 TI - Assessing the Impact of Pharmacist Maldistribution on Self-Reported Health in Rural and Urban Counties in the us. PMID- 27202752 TI - Incidence and Risk of Cardiotoxicity Induced by Sunitinib in Patients with Renal Cell Carcinoma: A Population-Based Case-Control Study in Chinese Population. PMID- 27202751 TI - Persistence in Health Expenditures by the Elderly in Taiwan: Predicting the Top 10% Users. PMID- 27202753 TI - Drug Therapy Problems in Patients on Antihypertensives with Antidiabetic Drugs in Two Tertiary Health Institutions in Niger Delta Region, Nigeria. PMID- 27202754 TI - Updating Characteristics of Type 2 Diabetes Mellitus Patients in China: Surveys in year 2008 and 2011-12. PMID- 27202755 TI - Health Care Utilization and Costs After Warfarin Discontinuation Among Patients with Non-Valvular Atrial Fibrillation. PMID- 27202756 TI - Nursing Diagnosis and Some Physiological Signs and Their Changes During the Arterial Hypertension. PMID- 27202757 TI - Clinical Characteristics Among Hypertension Patients with Diabetes in Shanghai, China. PMID- 27202758 TI - Association of Colchicine with Primary and Secondary Cardiovascular Events in Peritoneal Dialysis Patients: A Propensity Score Analysis. PMID- 27202759 TI - Effectiveness of Cardiac Resynchronization Therapy in Patients with Mild-Moderate Heart Failure: A Systematic Review and Bayesian Approach Network Meta-Analysis. PMID- 27202760 TI - A Comparison of Preferences for the Benefits and Risks of Statins Among Korean Physicians and Patients Using a Discrete-Choice Experiment. PMID- 27202761 TI - Effectiveness of Catheter-Based Renal Denervation for Treatment Resistant Hypertension - Results of a Systematic Review and Meta-Analysis. PMID- 27202762 TI - Long Term Follow up of Primary and Secondary Prevention Implantable Cardioverter Defibrillator Patients: "Real-World" Data from the Island of Crete. PMID- 27202763 TI - Hypertension Treatment in Chronic Kidney Disease Stage 3, 4 and 5: A Hospital Based Cross-Sectional Study in Malaysia. PMID- 27202764 TI - Use of Beta Blocking Agents in Serbia in the Period from 2008 to 2012 Year. PMID- 27202765 TI - Use of Calcium Channel Blockers in Serbia in the Period from 2008 to 2012 Year. PMID- 27202766 TI - PROF DR Hasbullah Thabrany. PMID- 27202767 TI - Study of Medication Adherence in Diabetes Mellitus Patients with Hypertension. PMID- 27202768 TI - Efficacy of Ayurvedic Formulation in The Management of Essential Hypertension. PMID- 27202769 TI - A Retrospective Cost-Effectiveness Analysis of S-Amlodipine in China. PMID- 27202770 TI - Body Mass Index (BMI) as A Predictor of Outcome After Coronary Artery Bypass Grafting: An Asian Perspective. PMID- 27202771 TI - The Relationship Between Masked Hypertension and Obesity. PMID- 27202772 TI - Prevalence of Severe Treatment Resistant Hypertension and Eligibility for Catheter-Based Renal Denervation in Australia - a Preliminary Analysis. PMID- 27202773 TI - Medical Costs of Cardiovascular Diseases in Taiwan. PMID- 27202774 TI - Budget Impact of Left Atrial Appendage Occulusion in Patients with Atrial Fibrillation Contraindicated to Anticoagulation. PMID- 27202775 TI - Awareness of Hyperlipidemia Among University Students and Staff Member. PMID- 27202776 TI - Cost-Effectiveness Analysis of Fondaparinux Versus Enoxaparin in Non-St Elevation Acute Coronary Syndrome in Thailand. PMID- 27202777 TI - Cost-Effectiveness of Clopidogrel-Aspirin Versus Aspirin Alone for Acute Tia and Minor Stroke. PMID- 27202778 TI - Example of Analysis Utilizing Real World Data: Medical Cost Reduction by Advising Untreated-Hypertension Patients to Visit Doctors. PMID- 27202779 TI - How Likely Warfarin Pharmacogenetic Test to be Cost-Effective in Thailand: A Threshold Analysis. PMID- 27202780 TI - Antithrombotic Therapy and Direct Medical Costs in Patients with Acute Coronary Syndrome in Shanghai, China. PMID- 27202781 TI - Cost-Effectiveness of Treating Acute Coronary Syndrome Patients with Rivaroxban in Australia. PMID- 27202782 TI - A Cost-Utility Analysis of Calcium Channel Blockers (Ccbs) Compared with Angiotensin II Receptor Blockers (Arbs) In Preventing Stroke And Myocardial Infarction Among Hypertension Patients In The Taiwan. PMID- 27202783 TI - Comparative Cost-Effectiveness of CT Perfusion for Selecting Stroke Patients for Thrombolysis. PMID- 27202784 TI - The Cost-Effectiveness of Four Chinese Patent Medicine in the Treatment of Angina Pectoris in China. PMID- 27202785 TI - Markov Model-Based Economic Evaluation of Combination Therapy with Ezetimibe and Statin Monotherapy. PMID- 27202786 TI - The Integrated Care Pathway for Managing Post Stroke (ICAPPS) Patients in the Community: A Cost -Effectiveness Analysis. PMID- 27202787 TI - Cost-Effectiveness of Single-Pill Combination Therapy of Amlodipine/Atorvastatin Compared with Concurrent Two-Pill Therapy in Patients with Hypertension. PMID- 27202788 TI - Setting up the Right Scenarios for Cost-Effectiveness Analysis: An Example with Anticoagulants for Stroke Prevention in Atrial Fibrillation Patients in China. PMID- 27202789 TI - Does Blood Lipid Screening is Cost-Effectiveness Among Chinese Adults Aged 45 And Above? PMID- 27202790 TI - Economic Evaluation of Catheter-Based Renal Denervation for Patients with Resistant Hypertension in Korea. PMID- 27202791 TI - Cost Effectiveness of Catheter-Based Renal Denervation for Treatment Resistant Hypertension - an Australian Payer Perspective. PMID- 27202792 TI - A Cost Utility Analysis of Amlodipine Compared with Angiotensin II Receptor Blockers in Preventing Stroke and Myocardial Infarction Among Hypertension Patients in the Philippines. PMID- 27202793 TI - Association Between Baseline Socio-Demographic and Clinical Characteristics and Total Annual Cost of Patients Subjected to CRMDS Implantation. PMID- 27202794 TI - An Evaluation Of Medication Adherence In Hypertensive Patients Using The Theory Of Planned Behavior. PMID- 27202795 TI - Dose Titration, Persistence, and Adherence to Statin Therapy Among Patients with High-Risk Vascular Disease in Japan. PMID- 27202796 TI - Discontinuation/Interruption of Warfarin Therapy in Patients with Non-Valvular Atrial Fibrillation. PMID- 27202797 TI - Pharmaceutical Care Patients of Chronic Diseases with Polypharmacy and Cost Saving. PMID- 27202798 TI - Effect of Pharmaceutical Care on the Quality of Life in the Patients of Coronary Artery Disease. PMID- 27202799 TI - Mental Component of the Quality of Life Increased According to the Level of Obesity. PMID- 27202800 TI - Treatment and Monitoring of Venous Thromboembolism (VTE) Among Hospitalized Patients in China. PMID- 27202801 TI - Drug Utilization Research in Geriatric Patients with Chronic Ischemic Heart Disease. PMID- 27202802 TI - High BMI and Belly fat Correlate with Prevalence of Hypertension And Diabetes: A Cross Sectional Study In Sedentary Urban Popultaion Of Delhi. PMID- 27202803 TI - Lipid Control After Percutaneous Coronary Intervention (PCI) in China. PMID- 27202804 TI - Association of Dietary Patterns and Blood Pressure in Taiwanese Females. PMID- 27202805 TI - Effects of the Pay-for-Performance Program on Health Outcomes of Diabetic Patients. PMID- 27202806 TI - A Retrospective, Longitudinal Study to Investigate the Change of LDL-C Level and Pharmaceutical Intervention by Using Japanese Health Care Checkup Database. PMID- 27202807 TI - Policy Evaluation of Anti-Hypertensive Drugs in Mumbai, India. PMID- 27202808 TI - Efficacy and Safety of Five New Antidepression Drugs A Network Meta Analysis. PMID- 27202809 TI - Minimum Clinically Important Difference in the Global Assessment Functioning in Patients with Schizophrenia. PMID- 27202810 TI - Functional Impairment and Cognitive Dysfunction in Depressed Patients in South Korea: Results of Perform-K. PMID- 27202811 TI - Burden Associated with Agitation in Schizophrenia. PMID- 27202813 TI - Minimum Clinically Important Difference in the Calgary Depression Scale for Schizophrenia. PMID- 27202812 TI - Comparative Effectiveness in Terms of Treatment Discontinuation of Orodispersable Versus. Standard Oral Olanzapine Tablets in Non-Adherent Patients: Results from a 1-Year European Outpatient Observational Study. PMID- 27202814 TI - Evolution of Depressive Status in Patients with Schizophrenia: An Analysis of Patient Trajectories. PMID- 27202816 TI - Prevalence of Major Depressive Disorder in China. PMID- 27202815 TI - Evolution of Presence of Predominant Negative Symptoms in Patients with Schizophrenia. PMID- 27202817 TI - Global Economic Burden of Schizophrenia: A Systematic Review. PMID- 27202818 TI - Economic Burden of Dementia in Singapore: Preliminary Results. PMID- 27202819 TI - Burden of Illness of Dementia in China. PMID- 27202820 TI - Economic Burden of Schizophrenia in China: Based on Medical Insurance Database from Guangzhou City. PMID- 27202821 TI - Health Insurance Cost of Anxiety in Hungary: A Cost of Illness Study. PMID- 27202822 TI - Comparison of Medical Costs and Utilization Associated With Use of Ziprasidone and Olanzapine Among Schizophrenia and Bipolar Disorder Patients. PMID- 27202823 TI - Health Insurance Cost of Alzheimer Dementia In Hungary: A Cost of Illness Study. PMID- 27202824 TI - To Study the Treatment Pattern and Cost of Illness in Bipolar Disorder Patients in Tertiary Care Hospital in South India. PMID- 27202825 TI - Cost and Resource Use of Managing Major Depressive Disorder (MDD) in China. PMID- 27202826 TI - Disease Management, Resource Utilisation and Associated Cost for Moderate and Severe Dementia Patients in China: Results from a Delphi Panel. PMID- 27202827 TI - Examining Opioid-Dependent Chronic Pain Patients Experiences On Buprenorphine Maintenance Therapy In The Texas Workers Compensation System: Pilot Study - Part 2. PMID- 27202828 TI - Comparative Pharmacoeconomics Studies of Treatment for Major Depressive Disorder in China. PMID- 27202829 TI - Economic Evaluation of Alzheimer. PMID- 27202830 TI - General Beliefs About Medicines Among Depressed Patients in Saudi Arabia. PMID- 27202831 TI - Predictors of Adherence to Antidepressant Ymedications in Saudi Arabia Y. PMID- 27202832 TI - Future Impact of Dementia on the Caregiver in China. PMID- 27202833 TI - Importance Of Remission In Patients With Major Depressive Disorder In Korea For Improving Health-Related Quality Of Life And Economic Burden. PMID- 27202834 TI - Evaluation of Factors Affecting Sales of Prescription. PMID- 27202835 TI - Pattern of Antidepressant Utilization and Cost in Iran From 2007-2011 in Comparison to European and East Asian Countries and Literature Review. PMID- 27202836 TI - Outpatient Treatment of Adolescents with Antidepressants in Japan. PMID- 27202838 TI - Public Beliefs and Attitudes about Schizophrenia, Major Depression and Psychotropic Medication in Tunisia. PMID- 27202837 TI - Prevalence and Predictors of Clinically Undiagnosed Cognitive Impairment Among Older Residents of Nursing Homes in Association with HRQOL. PMID- 27202839 TI - The Use of Integrated Concept Mapping to Develop the Dementia Care Model by Community Participation. PMID- 27202840 TI - The Effects of Gallium Chloride on Apoptosis Osteoporosis Model of Rats Caused by Tretinoin Acid. PMID- 27202842 TI - Outcomes in Severe Osteoporotic Women in Korea Using Sequential Treatment. PMID- 27202841 TI - The Effect of Dietary Selenium Intake in The Gene Expression of P38, P65, and Caspase-3 in Fluorosis Patients. PMID- 27202844 TI - Prescribing Pattern and Cost Analysis on (Dmard's) Disease Modifying Anti Rheumatoid Drugs in Rheumatoid Arthritis Patients of a Tertiary Care Teaching Hospital in South India - a Cross Sectional Study. PMID- 27202843 TI - A Comparative Clinical Evaluation of Trayodashanga Guggulu and Mustadiyapana Yoga Basti in Gridhrasi. PMID- 27202845 TI - Metabolic Disorders, Osteoporosis and Fracture Risk in Asia: A Systematic Review. PMID- 27202846 TI - Encumberance to the Treatment of Osteoporosis: Physicians and Patient Perception. PMID- 27202847 TI - The Research of Effects of Iguratimod(T-614) on the Apoptosis of Peripheral Blood Mononuclear Cell and TH1 in Rheumatoid Arthritis. PMID- 27202848 TI - Estimating The Impact Of Expanding Access To Celecoxib For Osteoarthritis Patients In China. PMID- 27202849 TI - The Costs of Major and Minor Cycling Accidents in Tasmania, Australia. PMID- 27202850 TI - Cost-Effectiveness of denosumab vs. Brand or generic zoledronic acid in patients with prostate cancer in kazakhstan. PMID- 27202851 TI - Cost-Effectiveness of Denosumab vs. Brand or Generic zoledronic Acid in Patients with Breast Cancer in Kazakhstan. PMID- 27202852 TI - Calculating Indirect Costs - Differences Caused by Various Approaches to Unit Costs. Results of Move to Work Study (M2W). PMID- 27202853 TI - The Econimic Cost of Rheumatoid Arthritis in Taiwan. PMID- 27202854 TI - Economic Burden of Childhood Injury: A Review. PMID- 27202856 TI - Cost-Effectiveness Analyses of Screening and Treatment Strategies for Postmenopausal Osteoporosis in Chinese Women. PMID- 27202855 TI - Health Care Resource Requirements and Costs During the Recovery Phase of Fasciectomy for the Treatment of Dupuytren's Contracture: Clinician Survey. PMID- 27202857 TI - A Kinematic Comparison of Overground and Treadmill Walking. PMID- 27202858 TI - Cost Utility Analysis of Infliximab for the Treatment of Severe Rheumatoid Arthritis in Thailand. PMID- 27202859 TI - Relationship Between Hip Muscle Strength and Kinematics of the Knee Joint. PMID- 27202860 TI - Assessment of Medication Adherence in Rheumatoid Arthritis Patients in a Tertiary Care Hospital. PMID- 27202861 TI - Estimating Health Care Resource Utilization of Patients with Rheumatoid Arthritis in Taiwan Using a National Claims Database. PMID- 27202862 TI - Clinical Research for the Effectiveness and Economic Value of Qinxitong in the Patients with Ra in China. PMID- 27202863 TI - Care Needs for Rheumatoid Arthritis from Patient Perspectives: A Qualitative Study from Singapore General Hospital. PMID- 27202864 TI - Exploring the Willingness-to-Pay for Innovative Treatments for Immunology and Oncology in China. PMID- 27202866 TI - Suitability research on the Evaluation of EQ-5Q and SF-6D Scale for the Quality of Life in Patients with Osteoarthritis. PMID- 27202865 TI - Exploring the Willingness-to-Pay for Biologic Treatments In Immunology Diseases in China. PMID- 27202867 TI - Stakeholder Evidence Requirements and Price Expectations for Biosimilars in Three Asian Markets. PMID- 27202868 TI - Closing the Gap: Reduced Delay to Drug Marketing Approval Between The West and Asia. PMID- 27202869 TI - Inhaled Anticholinergics and Risk for Acute Urinary Retention: A Case-Crossover and Case-Time-Control Study. PMID- 27202870 TI - COUGH AS A KEY SYMPTOM IN ASTHMA, ALLERGIC RHINITIS, COPD AND RHINOSINUSITIS AND ITS IMPACT IN ASIA. PMID- 27202871 TI - The Impact of Psychological Treatment of Rheumatic Patients With Mental Health. PMID- 27202872 TI - Health Literacy and Health Care Utilization Among Adults with Osteoporosis. PMID- 27202873 TI - The Effectiveness and Safety of Febuxostat : An Experience in Medical Center in Taiwan. PMID- 27202874 TI - Factors Affecting the Out-Come in Hospital Acquired Pneumonia. PMID- 27202876 TI - Pollen Morphology and Total Protein of Taraxacum Officinale and Aster Alpinus. PMID- 27202875 TI - A Method to Investigate Seasonal Variation in Hospitalization for Copd in A Midwestern US State. PMID- 27202877 TI - Analysis of Factors Causing Chronic Obstructive Pulmonary Disease in Eastern Region of China. PMID- 27202878 TI - Incidence-Based Cost of Asthma in Vietnam. PMID- 27202879 TI - Health Care Utilization and Cost of Management in Patients with Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Thailand. PMID- 27202880 TI - Cost-Benefit Analysis of Bacterial Lysates for Chronic Obstructive Pulmonary Disease in China. PMID- 27202881 TI - Economic Burden of Pediatric Atopic Dermatitis in Asia-Pacific: A Review of the Literature. PMID- 27202882 TI - Burden of Atopic Dermatitis in Indonesia, Malaysia, and Singapore: Estimates from a Mathematical Model. PMID- 27202883 TI - Comparison of Health Care Utilization and Costs for Patietns with Asthma by Severity and Health Insurance in Thailand: Using Generalized Linear Regression Model. PMID- 27202884 TI - Missing data Analysis in Longitudinal Studies: Findings from a Quality of Life Study in Malaysian Tuberculosis Patients. PMID- 27202885 TI - Resource Utilized in a Randomized Clinical Trial to Recruit Smokers with Low Motivation to Quit. PMID- 27202886 TI - Modeling the Cost-Effectiveness of 100% Whey-Based Partially Hydrolyzed Versus. Cow's Milk Infant Formula in the Prevention of Atopic Dermatitis in Singapore. PMID- 27202887 TI - Health Status in Adult Patients with Copd in Korea. PMID- 27202888 TI - Evaluation of Cost Effectiveness of OM-85 in China. PMID- 27202889 TI - Cost-Effectiveness of the Treatment of Respiratory Diseases of Xiyanping Injection : A Systematic Review. PMID- 27202890 TI - Perception Pattern Analysis of Self-Medication Practices Among People in Southern District of Karnataka, India. PMID- 27202891 TI - Duration of Treatment in Pulmonary Tuberculosis: are International Guidelines on the Management of Tuberculosis Missing Something? PMID- 27202892 TI - The Effect of Bacterial Lysates on Patients with Recurrent Respiratory Tract Infections: A Meta-Analysis. PMID- 27202893 TI - Smoking Cessation Treatment Patterns and Characteristics of Patients with Copd Who are Attempting to Quit in Urban China. PMID- 27202894 TI - Factors Contributing to Quality of Life in Copd in South Korea. PMID- 27202895 TI - Health-Related Quality of Life for Patients with Chronic Obstructive Pulmonary Disease in South Korea. PMID- 27202896 TI - Access to Asthma Medicines in Tehran; Iran. PMID- 27202897 TI - Economic Impact of Levalbuterol Versus Albuterol in Low-Income Population. PMID- 27202898 TI - Comparing the Efficacy of Anti-Vascular Endothelia Growth Factor Drugs for Treatment of Age-Related Macular Degeneration: a Clinical Literature Review and Meta-Analysis. PMID- 27202899 TI - Pharmacological Treatments in Pregnant Women with Psoriasis. PMID- 27202900 TI - The Economic Burden and their Predictors in Preschool Children with Dental Caries in Urban Beijing. PMID- 27202901 TI - Burden of Wet Age-Related Macular Degeneration in China. PMID- 27202902 TI - Cost-Effectiveness Analysis of Latanoprost Compared with Dorzolamide/Timolol Fixed Combination for the Treatment of Open-Angle Glaucoma and Ocular Hypertension Patients in Korea. PMID- 27202903 TI - A Prospective Pharmacoeconomic Study of Bilateral Prostaglandin/ Prostamide Therapy for Lowering Intraocular Pressure (Iop) in the Patients in South India. PMID- 27202904 TI - A Literature Review on Cost-Effectiveness of Treatments for Wet Age-Related Maculare Degeneration. PMID- 27202905 TI - Economic Evaluation of Bevacizumab Versus Ranibizumab in Neovascular Age-Related Macular Degeneration in China. PMID- 27202906 TI - Cost Utility Analysis of Ustekinumab for the Treatment of Moderate to Severe Chronic Plaque Psoriasis in Thailand. PMID- 27202907 TI - Adherence, Predicting Factors and Satisfaction of Patients on Glaucoma Therapy: Findings From a Cross-Sectional Study in Korea. PMID- 27202908 TI - Utility Values Among Myopic Patients in Mainland China. PMID- 27202909 TI - Prescribing Patterns and Expenditures for Otitis Media-Related Antibiotics for Children in the Texas Medicaid Program. PMID- 27202910 TI - Second Generation Azoles for Prophylaxis Against Invasive Fungal Infection: is Voriconazole Equivalent to Posaconazole in Haematology Patients? PMID- 27202911 TI - Interchangeability Study of Multisource Paracetamol 500mg Tablets, Produced in Mongolia. PMID- 27202912 TI - Clinical Efficacy of the Polyherbal Ayurvedic Medicine in The Management of Overweight. PMID- 27202913 TI - Prescribing Patterns and Treatment Outcomes in North Indian Female Patients with Chronic Low Back Pain. PMID- 27202914 TI - Health Economic Evaluation Comparing Iv Iron Ferric Carboxymaltose, Iron Sucrose and Blood Transfusion For Treatment of Patients with Iron Deficiency Anemia (Ida) in Singapore. PMID- 27202915 TI - Cost Effectiveness 0f Propofol Verses Thiopental in Icu Wards. PMID- 27202916 TI - Understanding the Japanese General Public's Rationale for Trades in a Time-Trade Off Assessment for Systemic Lupus Erythematosus. PMID- 27202917 TI - Prevalence of Neuropathic Pain in Korean Patients Scheduled for Lumbar Spine Surgery and their Health Related Quality of Life: Nationwide, Multicenter, Prospective, Cross-Sectional, Observational Study. PMID- 27202918 TI - The Performance- Volume Limit Decreased the DRG Based Acute Care Hospital Financing in hungary. PMID- 27202919 TI - Pricing and Market Access of Orphan Drugs in Asia: a Comparative Study Across Growth Markets. PMID- 27202920 TI - Assesing the Impact of Patent Loss on Overall Revenues and Stocks Price of Pharmaceutical Companies. PMID- 27202921 TI - Factors Affecting the Selection of Sore Throat Lozenge of Drugstore's Customer at Nakornpathom Municipality, Nakornpathom Province, Thailand. PMID- 27202922 TI - Study of Technical Conditions for Improvement of Angiographic Image Quality. PMID- 27202923 TI - The Socioeconomic Costs of the Undertreatment of Pain. PMID- 27202924 TI - Impact of Drug Policy on Improving Access to Medicines In Delhi. PMID- 27202925 TI - Price Comparison Between the Essential and Non-Essential Anti-Infective Medicines Among National Reimbursement Drug List in China. PMID- 27202926 TI - Pharmaceutical Pricing and Market Competition: An Empirical Study Based on Anti Infective Drugs In Tianjin, China. PMID- 27202927 TI - Pharmacological Basis for the Medicinal use of Almonds in Cardiovascular Disorders. PMID- 27202928 TI - Co-Administration of Turmeric Potentiates Preventive Effect of Black Seeds in Metabolic Syndrome. PMID- 27202929 TI - The Impact on Drug Price and Patiet Selection of National Essential Drug System: Evidence From Inpatient Records from Insurance Reimbursement Data. PMID- 27202930 TI - Questionnaire Analysis on Pharmacists Role and Drug Reimbursement List Adjustment Mechanism Under the Current China Health Insurance System. PMID- 27202931 TI - Review Of Reference Pricing Effects On Pharmaceuticals. PMID- 27202932 TI - Review on Medicines Prices and Availability in Indonesia: 2004 To 2012. PMID- 27202933 TI - An Analysis Of Determinants Of New And Bland-Name Drugs Prescription Behavior Among Japanese Physicians. PMID- 27202934 TI - How do Organizational Arrangements of the Pharmaceutical Supply System Affect Availability to Essential Medicines in Rural China? PMID- 27202935 TI - Use of Medications in the Event of Job Loss. PMID- 27202936 TI - Drug Utilization Pattern for the Treatment of Septic Shock in the ICU: A Comparison Between Survivors and Non-Survivors in a Tertiary Care Teaching Institute. PMID- 27202937 TI - Recent Regulatory Reforms to Ensure Patient Safety in Clinical Research In India. PMID- 27202938 TI - Provincial Hospital Tendering in China: Evaluating The Impact on Price. PMID- 27202939 TI - Pricing and Reimbursement Policy Updates in Asia. PMID- 27202940 TI - Classification of Drugs Bringing from Abroad in Turkey According to Their Atc Codes. PMID- 27202941 TI - Drug Access Is Improved By The Essential Drug System And "Low-Priced Drug" Policy In China. PMID- 27202942 TI - The Dynamics Of Prices And Quantities Of New Drugs Under Taiwan's National Health Insurance Program. PMID- 27202943 TI - Potential Prescriber Mapping In Rural Location Of South India. PMID- 27202944 TI - A Qualitative Exploration Of Malaysian Doctors' Perceptions Towards Complementary And Alternative Medicines (Cam). PMID- 27202945 TI - Health Implications of the MTM Eligibility Criteria In The Affordable Care Act Across Racial And Ethnic Groups. PMID- 27202946 TI - Patients And Doctors Working Together To Improve Health Service: Difficulties And Challenges In Between In China. PMID- 27202947 TI - Drug Access Through Sharing Public And Individual Responsibilities In The Public Health Care System Of Singapore. PMID- 27202948 TI - Evaluation Of The Economic Impact Of Specialist Outpatient Clinic Pharmacy Interventions In A Tertiary Institution, Singapore. PMID- 27202949 TI - Estimating The Costs Of Specialist Out-Patient Services In A Public Hospital. PMID- 27202950 TI - How The Implementation Of Drug Zero Markup Policy Will Affect Health Care Expenditure In Hospitals: Observation And Prediction Based On Zhejiang Model. PMID- 27202951 TI - Comprehensive Health Insurance Schme and Health Care Utilization: A Case Study Among Insured Households in Kerala, India. PMID- 27202952 TI - The Impact of the Income Per Capita in Chinese Family on Medical Expenditure. PMID- 27202953 TI - Evaluating the Impact of Drug Dispensing Systems on the Safety and Efficacy in a Singapore Outpatient Pharmacy. PMID- 27202954 TI - Evaluation of a Multidisciplinary Home-Based Medication Review Program for Elderly Singaporeans. PMID- 27202955 TI - Evaluation of Adverse Drug Reaction (ADR) Monitoring and Reporting System in China. PMID- 27202956 TI - Correlation Between Poison Severity Asessment And Outcome In Organophosphate Poisoning In Tertiary Care Hospital. PMID- 27202957 TI - Detection and Evaluation of the Medication Errors in Different Hospitals in Province of the Punjab, Pakistan. PMID- 27202958 TI - Survey Findings on Evaluation of Traumatologist's Workload in Mongolia. PMID- 27202959 TI - Investigating the Knowledge of Pharmacists about Cosmetics Products in Pharmacies of Tehran (IRAN). PMID- 27202960 TI - Incidence of Drug Related Problem Admissions & Emergency Department Visits in a Secondary Care Hospital in South India. PMID- 27202962 TI - Quality Of Hospital Food And Its Safety Assessment. PMID- 27202961 TI - Cost Analysis Of Pharmaceutical Service In Hospital: A Case Study In A Tertiary Hospital In Sichuan, China. PMID- 27202963 TI - Association of Severity Assessment Tool with the Outcome of Organophosphorus Poisoning in Tertiary Care Teaching Hospital. PMID- 27202964 TI - Understanding the Need and Value of Surrogate Endpoints for Health Care Decision Making in Asia Pacific. PMID- 27202965 TI - Review of Taiwan Nhia's Two-Stage New Drugs Listing and Reimbursement Assessments (2013-Feb. 2014). PMID- 27202966 TI - An Analysis of Pricing Premiums Granted Through Submitting Local RCT and Pharmacoeconomics Data in Taiwan. PMID- 27202967 TI - Pharmacoeconomic Research and Application In 10 Asian Countries Between 2003 and 2013: A Systematic Review. PMID- 27202968 TI - Organization Potency and Human Resource. PMID- 27202969 TI - Study on Audit and Control System and its Current Situation. PMID- 27202970 TI - Implementation and Assessment of Periodic Safety Update Reporting System at Tertiary Care Teaching Hospital, Karnataka, India: A Drug Controller General of India Initiative. PMID- 27202971 TI - An Analysis of the Key Value Drivers for HTA Assessments In Taiwan. PMID- 27202972 TI - From Regulatory Approval to Subsidised Patient Access in the Asia-Pacific Region: A Comparison of Systems Across Australia, China, Japan, Korea, New Zealand, Taiwan And Thailand. PMID- 27202973 TI - A Comparison of Asian and Global Pharmaceutical Prices Using an EKS Method. PMID- 27202975 TI - Economic Impact of New Rural Cooperative Medical Scheme In China. PMID- 27202974 TI - Principles of External Price Referencing System - A Review. PMID- 27202976 TI - Regulatory Approval to Patient Access, an Evaluation of EU5 and us National Timing Differences. PMID- 27202977 TI - An Analysis of the Drivers of Pricing Premiums Granted to Innovative Products in Japan. PMID- 27202978 TI - Developing a Patient Centred Model for Clinicians to Individualise Cost Effective Treatment. PMID- 27202979 TI - Why it is Difficult for European to Understand the Chinese Market Access Process? PMID- 27202980 TI - Effects of Drug Cost Sharing Policy on the Drug Use, Financial Risks and Moral Hazard for the Health Insurance Beneficiaries. PMID- 27202981 TI - China Critical Illness Insurance Policy - The Recent Developments and Prospects. PMID- 27202982 TI - What are the Key Driving Factors Behind RSA Decisions In Australia? PMID- 27202983 TI - Pharmacoeconomics and its Applications - Emerging Role in India. PMID- 27202984 TI - Correlation of Recent HTA Decisions Between Taiwan and Korea: Implication for Launch Strategies. PMID- 27202985 TI - A Critical Review of Chinese Pharmacoeconomics Studies in the Last Five Years. PMID- 27202986 TI - Application Of The Methods of Evidence Based Medicine for the Analysis of European Health Systems and Health Policy Approaches. PMID- 27202987 TI - Fostering Patient Safety Culture in Hospital to Improve Health Service: Hospital Survey on Patient Safety Culture. PMID- 27202988 TI - Do HTA Processes Correlate With Reimbursement Recommendations? PMID- 27202989 TI - Training High-Level Local Researchers to Improve the Quality of Clinical Studies in Developing Countries: Challenge and Strategy. PMID- 27202990 TI - Research on Health Services Need and Utilization of the Rural Elderly Left at Home in Shaanxi Province, China. PMID- 27202991 TI - Hearing the Patient's Voice in Health Care: A Survey Analysis of Patients' Perceptions of Difficulties in Shared Clinical Decision-Making. PMID- 27202992 TI - Assessment of Rural Health Purchasing Arrangements In China. PMID- 27202993 TI - Assessing the Effectiveness AND Cost-Effectiveness of Audit and Feedback on Physician's Prescribing Indicators. PMID- 27202994 TI - The DA Vinci Surgical System: A Rapid Review of the Clinical and Economic Evidence. PMID- 27202995 TI - The Performance of the Pragmatic Strategy to Bring in Pharmacoeconomic Evidence for Drugs Reimbursement Decisions in Taiwan. PMID- 27202996 TI - Comparison of Economic Evaluation Guidelines Between Japan and Other Asian Countries. PMID- 27202997 TI - Benchmarking the Impact of HTA on New Medicines Development and Coverage Decision Making. PMID- 27202998 TI - What is the Status of Health Related Quality of Life Among Medical Representatives in India? PMID- 27202999 TI - Health Technology Assessment In Japan: History, Current Situation, and the Way Forward. PMID- 27203000 TI - Current Status and Deficiency of Hemostasis in Surgery: A Systematic Literature Review, Including Chinese Literature. PMID- 27203001 TI - The Impact of Unfamiliarity In Palliative Care Under Pharmacotherapeutic Aspect. PMID- 27203002 TI - Study of Antibiotic Prescription Pattern and Antibiotic Sesitivity in Surgery Patient in Tertiary Care Hospital. PMID- 27203003 TI - An Analysis of Quality of Care in the Respiratory Care Center Based on Services Provided by Physicians with Different Responsibilities and Specialties. PMID- 27203004 TI - Impact of Pharmacoeconomics Guidelines on the International Publications in China. PMID- 27203006 TI - Analysis on Policies of Biosimilar Market in China. PMID- 27203005 TI - Developing a Drug Price Reference Index in the Philippines. PMID- 27203007 TI - Current Situation of Health Care Organizations' Waste Management. PMID- 27203008 TI - Comparison on the Concept of Market Access of China and Western Countries. PMID- 27203009 TI - Evidences and Criteria Related to the Hospital Service Quality and Safety. PMID- 27203010 TI - Critical Evaluation of Labeling Requirements of Nutraceutical Brands. PMID- 27203011 TI - Model Based Medicine: A Next Frontier in Health Care. PMID- 27203012 TI - Priority Setting Of New Medical Interventions In Taiwan: A Multicriteria Decision Analysis. PMID- 27203013 TI - Feasibility of Pharmacoeconomic Evaluations of Traditional Chinese Medicine from the Perspectives of the Health Insurance Review & Assessment Service in South Korea. PMID- 27203014 TI - Risk-Sharing Agreements In Australia: Attitude Towards Risk-Sharing Arrangements With The Department Of Health For The Pbs-Listing Of Pharmaceuticals. PMID- 27203015 TI - Risk Sharing Agreement Considerations for Pharmaceuticals in China Makret. PMID- 27203016 TI - Collaborative Approach in Accessing Homogeneous Medical Data in Grid-Based Environment (Enhancing Diseases Classification). PMID- 27203017 TI - Challenges and Opportunities in the Malaysian Health Care System. PMID- 27203018 TI - The Coverage with Clinical Evidence-Informed Decisions (CCEDS) :A New Health Care Payment Model in China. PMID- 27203019 TI - Impact of Cigarette and Alcohol Use on Adverse Drug Reactions of Haart Therapy Among HIV/AIDS Patients. PMID- 27203020 TI - Archimedes: A Large Scale Simulation System for Health Care Research and its Applications for Asian Countries. PMID- 27203021 TI - Burden of Varicella in Asia-Pacific Countries: A Systematic Review and Critical Analysis. PMID- 27203022 TI - Effectiveness of Hand Hygiene Promotion in Relation to Level of Investment: A Systematic Review. PMID- 27203023 TI - Chronic Hepatitis C Prevalence and its Correlation with CD4 Cells and Liver Enzymes Among HIV Positive Patients: A Malaysian Scenario. PMID- 27203024 TI - Impact of Hepatitis B on Human Immunodeficiency Virus Patients in Malaysia: A Retrospective Study. PMID- 27203025 TI - Adverse Drug Reactions of Haart Therapy Among Hiv/Aids Patients Treated at Infectious Disease Clinic. PMID- 27203026 TI - Health Care-Associated Infection Prevalence Among Grade a Tertiary Hospitals in China: A Meta-Analysis. PMID- 27203027 TI - Influenza Vaccination In Japan Among The General Population And High-Risk Groups. PMID- 27203028 TI - Clinical Outcomes and Hospital Costs Associated with Empirical Treatment of Hospital-Acquired Pneumonia with Vancomycin or Linezolid in a Chinese Tertiary Care Hospital: A Retrospective Cohort Study. PMID- 27203029 TI - A Retrospective Cohort Study of Risk Factors for Death Among Humman Immunodeficiency Virus Infected Adult Patients. PMID- 27203030 TI - Hospital Quality Of Infection Control. PMID- 27203031 TI - Influenza Vaccination in China Among the Urban Population and High-Risk Groups. PMID- 27203032 TI - Cost-Effectiveness of Antiviral Therapy for Chronic Hepatitis B: A Systematic Review. PMID- 27203033 TI - Economic Evaluation on Hepatitis B Vaccination Strategies for Preventing Mother To-Child Transmission in China. PMID- 27203034 TI - Direct Costs of Treatment of Skin Drug Reactions Induced by Antibiotics in Perspective of Public Payer and Service Provider. PMID- 27203035 TI - Cost-Effectiveness of Infant Vaccination with 13-Valent Versus 10-Valent Pneumococcal Conjuvate Vaccine in Korea. PMID- 27203036 TI - Survey of Treatment Costs to Hepatitis C in China. PMID- 27203037 TI - Cost-Effectiveness of Hepatitis a Vaccination in Indonesia. PMID- 27203038 TI - The Cost-Effectiveness of Combined Vector-Control and Vaccination Strategies on Prevention of Dengue Fever: A Dynamic Model-Based Analysis. PMID- 27203039 TI - Cost-Effectiveness of Posaconazole Versus Fluconazole or Itraconazole in the Prophylaxis of Invasive Fungal Infections Among Neutropenic Patients in Thailand. PMID- 27203040 TI - The Cost-Effectiveness Analysis of Two Pegylated Interferon ALFA Treatment for Chronic HCV Infection in China. PMID- 27203041 TI - Cost-Effectiveness of Maternal Immunisation for Pertussis in New Zealand. PMID- 27203042 TI - Assessment of Quality of Life in Human Immunodefieciency Virus Positive Patients with Adverse Reactions to Antiretroviral Therapy in Tertiary Care Hospital. PMID- 27203043 TI - Effect of Health Education Program on Knowledge, Attitude, Practice and Health Related Quality of Life in Hepatitis-B Patients. PMID- 27203044 TI - Meta-Analysis of Xuebijing Joint Ulinastatin Treating Sepsis. PMID- 27203045 TI - Cost-Utility Analysis of Optimal Dosing of Oseltamivir Under Pandemic Influenza Using a Novel Approach: Linking Health Economics and Transmission Dynamic Models. PMID- 27203046 TI - How can a Multilevel Promotion of Breastfeeding Reduce the Required Budget for Rotavirus Vaccination in Indonesia? PMID- 27203047 TI - Cost-Utility Analysis of 10- and 13-Valent Pneumocococcal Conjugate Vaccines in the Philippines. PMID- 27203049 TI - The Differences Between Infectious & Parasitic Drug Approvals in Japan and the USA. PMID- 27203048 TI - An Analysis Of The Utilization Of Cephalosporins From 2007 To 2011 In Guangdong Province Of China. PMID- 27203050 TI - Population Access to Rotavirus Vaccination in Industrialized Countries: Lessons Learnt from Current Experience. PMID- 27203051 TI - Ivacaftor for Patients with Cystic Fibrosis: Clinical Efficacy and Cost Effectiveness. PMID- 27203052 TI - Spending on HIV and AIDS in Indonesia: The Role of Government and Other Public Source of Fund to Maintain Quality and Equity. PMID- 27203053 TI - Social Aspects of HCV Treatment In Kazakhstan. PMID- 27203054 TI - Economic Burden of Drug use in Patients with Alzheimer's Disease at Phramongkutklao Hospisstal and Medical College, Thailand: A 5-Year Trend Analysis. PMID- 27203055 TI - Treatment Reasons, Resource use and Costs of Hospitalisations in People with Parkinson's: Results from a Large Rct. PMID- 27203056 TI - Alzheimer's Disease Caregiver Burden in Japan and the 5 E.U. PMID- 27203057 TI - The Impact of Mutliple Sclerosis Severity on Quality of Life, Stress, Depression and Social Support Needs. PMID- 27203058 TI - Best Practices and Key Challenges in Cost-Effectiveness Modelling of Multiple Sclerosis Therapies. PMID- 27203059 TI - Tadalafil in Benign Prostatic Hyperplasia: Protocol for the Systematic Review of Adverse Events. PMID- 27203060 TI - Impact of Copayment Reduction or Exemption Programme on Generic Drug Utilisation: the Specified Disease Treatment Research Programme in Japan. PMID- 27203061 TI - Reversal of Chronic Fatigue Induced Alterations by Sesamol in Mice: Evidence for Involvement of Oxidative Stress And Inflammatory Pathway. PMID- 27203062 TI - Assessment of Outpatient Physiotherapy Services in Diseases of the Nervous System in Hungary. PMID- 27203063 TI - Age and Gender Distribution of Outpatient Care Physiotherapy Services for Cerebral Palsy and Other Paralytic Syndromes in Hungary. PMID- 27203064 TI - Acetyl-L-Carnitine for the Treatment of Peripheral Neuropathic Pain: a Systematic Review and Meta-Analysis. PMID- 27203065 TI - Financial Implications to Taiwan Health System from Changing the Dialysis Modality Mix. PMID- 27203066 TI - C5a Receptor Antagonist Protects Mice from Uropathogenic Escherichia Coli-Induced Kidney Infection. PMID- 27203067 TI - Activation of Endogenous Anti-Inflammatory Mediator Cyclic Amp Confers Protection in Murine Acute Pyelonephritis Induced by Uropathogenic E Coli. PMID- 27203068 TI - Epidemiology of End Stage Renal Disease Patients on Hemodialysis for Hospital Readmissions. PMID- 27203069 TI - Prevalence and Associated Complication of Acute Kidney Injury Among Dengue Patients. PMID- 27203070 TI - Budget impact analysis of peritoneal dialysis versus. Conventional in-center hemodialysis in malaysia. PMID- 27203071 TI - Health and economic impact of combination therapy vs. Monotherapy for treatment of benign prostatic hyperplasia in hong kong. PMID- 27203072 TI - Cost-Effectiveness of Percent Free Psa for Prostate Cancer Detection in Chinese Men with a Total Psa of 4.0-10.0 Ng/Ml. PMID- 27203073 TI - Economic Evaluation of the Treatments for Hyperphosphatemia Among Patients with Chronic Kidney Disease: A Review. PMID- 27203074 TI - Patient Reported Outcomes(Pros) in Patients with Lower Urinary Track Symptom(Luts)/Benign Prostatic Hyperplasia(Bph) Accompanied with Overactive Bladder(Oab) in Korea. PMID- 27203075 TI - A Comparison of Patient-Reported and Laboratory Outcomes Between Hemodialysis and Peritoneal Dialysis Patients in a Multi-Ethnic Asian Population. PMID- 27203076 TI - Direct Medical Costs for Inpatient Treatment of Chronic Renal Failure in Guangzhou, China. PMID- 27203077 TI - Translation and Validation of Kidney Disease and Quality of Life (Kdqol-Sftm 1.2) Instrument to Measure Health Related Quality of Life Of Indian Patients with Kidney Disease. PMID- 27203078 TI - Correction: Correction: Engineered Promoters for Potent Transient Overexpression. AB - [This corrects the article DOI: 10.1371/journal.pone.0152449.]. PMID- 27203079 TI - Selective Retention of an Inactive Allele of the DKK2 Tumor Suppressor Gene in Hepatocellular Carcinoma. AB - In an effort to identify the functional alleles associated with hepatocellular carcinoma (HCC), we investigated 152 genes found in the 4q21-25 region that exhibited loss of heterozygosity (LOH). A total of 2,293 pairs of primers were designed for 1,449 exonic and upstream promoter regions to amplify and sequence 76.8-114 Mb on human chromosome 4. Based on the results from analyzing 12 HCC patients and 12 healthy human controls, we discovered 1,574 sequence variations. Among the 99 variants associated with HCC (p < 0.05), four are from the Dickkopf 2 (DKK2) gene: three in the promoter region (g.-967A>T, g.-923C>A, and g.-441T>G) and one in the 5'UTR (c.550T>C). To verify the results, we expanded the subject cohort to 47 HCC cases and 88 healthy controls for conducting haplotype analysis. Eight haplotypes were detected in the non-tumor liver tissue samples, but one major haplotype (TAGC) was found in the tumor tissue samples. Using a reporter assay, this HCC-associated allele registered the lowest level of promoter activity among all the tested haplotype sequences. Retention of this allele in LOH was associated with reduced DKK2 transcription in the HCC tumor tissues. In HuH-7 cells, DKK2 functioned in the Wnt/beta-catenin signaling pathway, as an antagonist of Wnt3a, in a dose-dependent manner that inhibited Wnt3a-induced cell proliferation. Taken together, the genotyping and functional findings are consistent with the hypothesis that DKK2 is a tumor suppressor; by selectively retaining a transcriptionally inactive DKK2 allele, the reduction of DKK2 function results in unchecked Wnt/beta-catenin signaling, contributing to HCC oncogenesis. Thus our study reveals a new mechanism through which a tumor suppressor gene in a LOH region loses its function by allelic selection. PMID- 27203080 TI - Total Effective Xenoestrogen Burden in Serum Samples and Risk for Breast Cancer in a Population-Based Multicase-Control Study in Spain. AB - BACKGROUND: Most studies on endocrine-disrupting chemicals and breast cancer have focused on single compounds and have produced inconclusive findings. OBJECTIVES: We assessed the combined estrogenic effects of mixtures of xenoestrogens in serum and their relationship to breast cancer risk. METHODS: A total of 186 incident pretreatment breast cancer cases and 196 frequency-matched controls were randomly sampled from a large population-based multicase-control study in Spain. The total effective xenoestrogen burden attributable to organohalogenated xenoestrogens (TEXB-alpha) and endogenous hormones and more polar xenoestrogens (TEXB-beta) was determined in serum samples using high-performance liquid chromatography and E Screen bioassay. Odds ratios for breast cancer comparing tertiles of serum TEXB alpha and TEXB-beta were estimated using logistic models, and smooth risk trends were obtained using spline models. RESULTS: Cases had higher geometric mean TEXB alpha and TEXB-beta levels (8.32 and 9.94 Eeq pM/mL, respectively) than controls (2.99 and 5.96 Eeq pM/mL, respectively). The fully adjusted odds ratios for breast cancer (95% confidence intervals) comparing the second and third tertiles of TEXB-alpha with the first tertile were 1.77 (0.76, 4.10) and 3.45 (1.50, 7.97), respectively, and those for TEXB-beta were 2.35 (1.10, 5.03) and 4.01 (1.88, 8.56), respectively. A steady increase in risk was evident across all detected TEXB-alpha levels and a sigmoidal trend was observed for TEXB-beta. Individual xenoestrogens showed weak and opposing associations with breast cancer risk. CONCLUSIONS: This is the first study to show a strong positive association between serum total xenoestrogen burden and breast cancer risk, highlighting the importance of evaluating xenoestrogen mixtures, rather than single compounds, when studying hormone-related cancers. CITATION: Pastor-Barriuso R, Fernandez MF, Castano-Vinyals G, Whelan D, Perez-Gomez B, Llorca J, Villanueva CM, Guevara M, Molina-Molina JM, Artacho-Cordon F, Barriuso-Lapresa L, Tusquets I, Dierssen Sotos T, Aragones N, Olea N, Kogevinas M, Pollan M. 2016. Total effective xenoestrogen burden in serum samples and risk for breast cancer in a population based multicase-control study in Spain. Environ Health Perspect 124:1575-1582; http://dx.doi.org/10.1289/EHP157. PMID- 27203081 TI - Bile Acids and Dysbiosis in Non-Alcoholic Fatty Liver Disease. AB - BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is characterized by dysbiosis. The bidirectional effects between intestinal microbiota (IM) and bile acids (BA) suggest that dysbiosis may be accompanied by an altered bile acid (BA) homeostasis, which in turn can contribute to the metabolic dysregulation seen in NAFLD. This study sought to examine BA homeostasis in patients with NAFLD and to relate that with IM data. METHODS: This was a prospective, cross-sectional study of adults with biopsy-confirmed NAFLD (non-alcoholic fatty liver: NAFL or non alcoholic steatohepatitis: NASH) and healthy controls (HC). Clinical and laboratory data, stool samples and 7-day food records were collected. Fecal BA profiles, serum markers of BA synthesis 7-alpha-hydroxy-4-cholesten-3-one (C4) and intestinal BA signalling, as well as IM composition were assessed. RESULTS: 53 subjects were included: 25 HC, 12 NAFL and 16 NASH. Levels of total fecal BA, cholic acid (CA), chenodeoxycholic acid (CDCA) and BA synthesis were higher in patients with NASH compared to HC (p<0.05 for all comparisons). The primary to secondary BA ratio was higher in NASH compared to HC (p = 0.004), but ratio of conjugated to unconjugated BAs was not different between the groups. Bacteroidetes and Clostridium leptum counts were decreased in in a subset of 16 patients with NASH compared to 25 HC, after adjusting for body mass index and weight-adjusted calorie intake (p = 0.028 and p = 0.030, respectively). C. leptum was positively correlated with fecal unconjugated lithocholic acid (LCA) (r = 0.526, p = 0.003) and inversely with unconjugated CA (r = -0.669, p<0.0001) and unconjugated CDCA (r = - 0.630, p<0.0001). FGF19 levels were not different between the groups (p = 0.114). CONCLUSIONS: In adults with NAFLD, dysbiosis is associated with altered BA homeostasis, which renders them at increased risk of hepatic injury. PMID- 27203083 TI - Primary Care Use before Cancer Diagnosis in Adolescents and Young Adults - A Nationwide Register Study. AB - INTRODUCTION: Survival rates of cancer patients have generally improved in recent years. However, children and older adults seem to have experienced more significant clinical benefits than adolescents and young adults (AYAs). Previous studies suggest a prolonged diagnostic pathway in AYAs, but little is known about their pre-diagnostic healthcare use. This study investigates the use of primary care among AYAs during the two years preceding a cancer diagnosis. METHODS: The study is a retrospective population-based matched cohort study using Danish nationwide registry data. All persons diagnosed with cancer during 2002-2011 in the age group 15-39 years were included (N = 12,306); each participant was matched on gender, age and general practice with 10 randomly selected references (N = 123,060). The use of primary healthcare services (face-to-face contacts, blood tests and psychometric tests) was measured during the two years preceding the diagnosis (index date), and collected data were analysed in a negative binomial regression model. RESULTS: The cases generally increased their use of primary care already from 8 months before a cancer diagnosis, whereas a similar trend was not found for controls. The increase was observed for all cancer types, but it started at different times: 17 months before a diagnosis of CNS tumour, 12 months before a diagnosis of soft tissue sarcoma, 9 months before a diagnosis of lymphoma, 5-6 months before a diagnosis of leukaemia, bone tumour or GCT, and 3 months before a diagnosis of malignant melanoma. CONCLUSION: The use of primary care among AYAs increase several months before a cancer diagnosis. The diagnostic intervals are generally short for malignant melanomas and long for brain tumours. A prolonged diagnostic pathway may indicate non-specific or vague symptomatology and low awareness of cancer among AYAs primary-care personnel. The findings suggest potential of faster cancer diagnosis in AYAs. PMID- 27203082 TI - Experimental Infection of Rhodnius prolixus (Hemiptera, Triatominae) with Mycobacterium leprae Indicates Potential for Leprosy Transmission. AB - Leprosy is a chronic dermato-neurological disease caused by infection with Mycobacterium leprae. In 2013 almost 200,000 new cases of leprosy were detected around the world. Since the first symptoms take from years to decades to appear, the total number of asymptomatic patients is impossible to predict. Although leprosy is one of the oldest records of human disease, the mechanisms involved with its transmission and epidemiology are still not completely understood. In the present work, we experimentally investigated the hypothesis that the mosquitoes Aedes aegypti and Culex quinquefasciatus and the hemiptera Rhodnius prolixus act as leprosy vectors. By means of real-time PCR quantification of M. leprae 16SrRNA, we found that M. leprae remained viable inside the digestive tract of Rhodnius prolixus for 20 days after oral infection. In contrast, in the gut of both mosquito species tested, we were not able to detect M. leprae RNA after a similar period of time. Inside the kissing bug Rhodnius prolixus digestive tract, M. leprae was initially restricted to the anterior midgut, but gradually moved towards the hindgut, in a time course reminiscent of the life cycle of Trypanosoma cruzi, a well-known pathogen transmitted by this insect. The maintenance of M. leprae infectivity inside the digestive tract of this kissing bug is further supported by successful mice footpad inoculation with feces collected 20 days after infection. We conclude that Rhodnius prolixus defecate infective M. leprae, justifying the evaluation of the presence of M. leprae among sylvatic and domestic kissing bugs in countries endemic for leprosy. PMID- 27203084 TI - Role of Alanine Dehydrogenase of Mycobacterium tuberculosis during Recovery from Hypoxic Nonreplicating Persistence. AB - Mycobacterium tuberculosis can maintain a nonreplicating persistent state in the host for decades, but must maintain the ability to efficiently reactivate and produce active disease to survive and spread in a population. Among the enzymes expressed during this dormancy is alanine dehydrogenase, which converts pyruvate to alanine, and glyoxylate to glycine concurrent with the oxidation of NADH to NAD. It is involved in the metabolic remodeling of M. tuberculosis through its possible interactions with both the glyoxylate and methylcitrate cycle. Both mRNA levels and enzymatic activities of isocitrate lyase, the first enzyme of the glyoxylate cycle, and alanine dehydrogenase increased during entry into nonreplicating persistence, while the gene and activity for the second enzyme of the glyoxylate cycle, malate synthase were not. This could suggest a shift in carbon flow away from the glyoxylate cycle and instead through alanine dehydrogenase. Expression of ald was also induced in vitro by other persistence inducing stresses such as nitric oxide, and was expressed at high levels in vivo during the initial lung infection in mice. Enzyme activity was maintained during extended hypoxia even after transcription levels decreased. An ald knockout mutant of M. tuberculosis showed no reduction in anaerobic survival in vitro, but resulted in a significant lag in the resumption of growth after reoxygenation. During reactivation the ald mutant had an altered NADH/NAD ratio, and alanine dehydrogenase is proposed to maintain the optimal NADH/NAD ratio during anaerobiosis in preparation of eventual regrowth, and during the initial response during reoxygenation. PMID- 27203087 TI - The Impact of Meta-analyses on Medical Decisions. PMID- 27203086 TI - The Value of Contrast-Enhanced Ultrasonography and Contrast-Enhanced CT in the Diagnosis of Malignant Renal Cystic Lesions: A Meta-Analysis. AB - We compared the efficacy of contrast-enhanced ultrasound (CEUS) and contrast enhanced computed tomography (CECT) for the diagnosis of renal cystic lesions via a meta-analysis to determine the value of CEUS in the prediction of the malignant potential of complex renal cysts. Eleven studies were evaluated: 4 control studies related to CEUS and CECT, 3 studies related to CEUS and 4 studies related to CECT. According to the random effects model, the pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio for CEUS/CECT were 0.95/0.90, 0.79/0.85, 4.39/5.00, and 0.10/0.15, respectively. The areas under the summary receiver operating characteristic (AUCs-SROC) curves for the two methods were 94.24% and 93.39%, and the estimated Q values were 0.8805 and 0.8698, respectively. Comparing the Q index values of CEUS and CECT revealed no significant difference between the two methods (P>0.05). When compared with conventional CECT, CEUS is also useful for diagnosing renal cystic lesions in the clinic. PMID- 27203088 TI - Percentage of Blastulation on the Number and Function of Metaphase II Oocytes. AB - OBJECTIVE: Establish the number of metaphase II oocytes that are needed for optimum blastulation rate and to achieve a better rate of gestation. METHODS: Retrospective study. Women diagnosed with infertility. There were 110 women submitted to IVF/ICSI, excluding third day transfers and those with canceled cycles. After controlled ovarian stimulation, cultivation continued to blastocysts. RESULTS: Average age of the patients: 33.41. IVF technique: 73 patients, 66.4%; ICSI: 37 patients, 33.6%. Pregnancy: gestation: 57.3%; Non gestation: 42.7%. Mean number of oocytes in metaphase II: 7.5. CONCLUSION: The gestation rate coincides with the center's results (50-60%), reached with 7 mature oocytes. Mean blastulation rate was 39.2%. PMID- 27203085 TI - Combined Exposure to Simulated Microgravity and Acute or Chronic Radiation Reduces Neuronal Network Integrity and Survival. AB - During orbital or interplanetary space flights, astronauts are exposed to cosmic radiations and microgravity. However, most earth-based studies on the potential health risks of space conditions have investigated the effects of these two conditions separately. This study aimed at assessing the combined effect of radiation exposure and microgravity on neuronal morphology and survival in vitro. In particular, we investigated the effects of simulated microgravity after acute (X-rays) or during chronic (Californium-252) exposure to ionizing radiation using mouse mature neuron cultures. Acute exposure to low (0.1 Gy) doses of X-rays caused a delay in neurite outgrowth and a reduction in soma size, while only the high dose impaired neuronal survival. Of interest, the strongest effect on neuronal morphology and survival was evident in cells exposed to microgravity and in particular in cells exposed to both microgravity and radiation. Removal of neurons from simulated microgravity for a period of 24 h was not sufficient to recover neurite length, whereas the soma size showed a clear re-adaptation to normal ground conditions. Genome-wide gene expression analysis confirmed a modulation of genes involved in neurite extension, cell survival and synaptic communication, suggesting that these changes might be responsible for the observed morphological effects. In general, the observed synergistic changes in neuronal network integrity and cell survival induced by simulated space conditions might help to better evaluate the astronaut's health risks and underline the importance of investigating the central nervous system and long term cognition during and after a space flight. PMID- 27203089 TI - Non-Invasive Prediction of Blastocyst Formation by Day Three Embryo Culture Medium Mass Spectrometry Lipid Fingerprinting. AB - OBJECTIVE: To identify lipid markers of blastocyst formation by day three culture medium mass spectrometry (MS) fingerprinting. METHODS: For this study, 50 embryo samples from culture media were harvested on day three, from patients undergoing embryo transfers on day five. Samples were split into groups based on their degree of expansion and hatching status on day five (Complete-Blastocyst, n=25 and No-Blastocyst, n=25) and its secretomes were analysed by MS. Mass spectra fingerprinting was acquired using a Q-Tof spectrometer (LC-MS, Agilent 6550 iFunnel Q-TOF) equipped with an automated injector. The data was analysed using the principal component analysis (PCA) followed by a partial least square discrimination analysis (PLS-DA), combined with variable influence in the projection (VIP) scores. RESULTS: In total, there were 1,657 ions found, in which 165 ions were differently expressed between groups, with a fold chance >= 4x and P<0.001, in the t-test. PLS-DA showed a clear separation between the groups and among 15 VIPs selected by the program, 13 of them were highly expressed in the Complete-Blastocyst Group and two were expressed in the No-Blastocyts Group. Besides embryo status on day five, the PLS-DA was also able to classify samples according to patients' age. Lipids supposedly highly expressed in the Complete Blastocyst Group included: isoprenoids, diacylglycerols, sterols, fatty esters, secosteroids, phosphosphingolipids, glycerophosphates and diacylglycerophosphates, while fatty amides were suggested to be highly expressed in the No-Blastocysts Group. CONCLUSIONS: Day three culture medium MS is a promising approach for the identification of embryos that should be cultured until day five. PMID- 27203090 TI - Cost-Effectiveness of the Freeze-All Policy. AB - OBJECTIVE: To evaluate the cost-effectiveness of freeze-all cycles when compared to fresh embryo transfer. METHODS: This was an observational study with a cost effectiveness analysis. The analysis consisted of 530 intracytoplasmic sperm injection (ICSI) cycles in a private center in Brazil between January 2012 and December 2013. A total of 530 intracytoplasmic sperm injection (ICSI) cycles - 351 fresh embryo transfers and 179 freeze-all cycles - with a gonadotropin releasing hormone (GnRH) antagonist protocol and day 3 embryo transfers. RESULTS: The pregnancy rate was 31.1% in the fresh group and 39.7% in the freeze-all group. We performed two scenario analyses for costs. In scenario 1, we included those costs associated with the ICSI cycle (monitoring during controlled ovarian stimulation [COS], oocyte retrieval, embryo transfer, IVF laboratory, and medical costs), embryo cryopreservation of supernumerary embryos, hormone measurements during COS and endometrial priming, medication use (during COS, endometrial priming, and luteal phase support), ultrasound scan for frozen- thawed embryo transfer (FET), obstetric ultrasounds, and miscarriage. The total cost (in USD) per pregnancy was statistically lower in the freeze-all cycles (19,156.73 +/- 1,732.99) when compared to the fresh cycles (23,059.72 +/- 2,347.02). Even in Scenario 2, when charging all of the patients in the freeze-all group for cryopreservation (regardless of supernumerary embryos) and for FET, the fresh cycles had a statistically significant increase in treatment costs per ongoing pregnancy. CONCLUSIONS: The results presented in this study suggest that the freeze-all policy is a cost-effective strategy when compared to fresh embryo transfer. PMID- 27203091 TI - AMH as a Prognostic Factor for Blastocyst Development. AB - OBJECTIVE: To investigate the relationship between AMH blood levels and the likelihood of blastocyst formation. METHODS: Two hundred ninety-two patients, 22 44 years of age, undergoing routine explorations during spontaneous cycles that preceded assisted reproductive technologies at our Center, were studied. As the present study did not require previous submission to our Institutional Review Board. Serum AMH and FSH levels were measured and laboratory data was obtained after ovulation induction with an antagonist protocol. Participants were sorted into two different groups paired by age. The first group (No Blasto; n=219) involved women having no blastocyst formation; the second group (Yes Blasto group; n=73) was made up of those women who were considered eligible to undergo 5 days of embryo culture. Furthermore, we analyzed blastulation rate. Patients were divided according to the rate of blastocyst formation <0.43 (n=36) and >= 0.43 (n=37). The Statistical analysis was performed using SPSS version 20.0. We ran Student's t-test for independent samples and Pearson's correlation. A P < 0.05 was considered significant. RESULTS: AMH levels were statistically different (P=0.002) between the YES and NO blasto groups. Number of oocytes, MII oocytes and embryos were higher in Yes Blasto group. FSH levels were similar between the groups (P=0.149). Pearson correlation coefficient shows that the rate of blastocyst formation is inversely correlated to AMH levels. CONCLUSIONS: We conclude that patients that were considered eligible to undergo blastocyst formation have higher levels of serum AMH, however too high concentration of this hormone can be harmful to blastocyst development. PMID- 27203092 TI - Vitrification of Human Oocytes and its Contribution to In Vitro Fertilization Programs. AB - OBJETICVE: To study the cumulative pregnancy outcome, particularly in terms of live births, with the consecutive transfer of embryos from fresh and vitrified/warmed oocytes to infertile patients in a routine infertility program. METHODS: Patients were initially submitted to in vitro fertilization embryo transfer with fresh embryos, while surplus oocytes were vitrified with the Vitri Inga method. Patients who did not succeed to carry their gestation to term underwent a new cycle with embryos from their own warmed oocytes. Some of the patients participating in the first warming cycle, who still possessed surplus oocytes, underwent a second warming cycle. Clinical and pregnancy outcomes obtained with fresh and warming cycles were compared using the chi-square test at a level of significance of 5%. RESULTS: Of the 211 participating patients, 97 (46%) got pregnant with fresh embryo transfer, and 69 (32.7%) carried their pregnancies to term. Of the patients participating in the first and second warming cycles, 32/100 (32%) and 6/20 (30.0%) resulted in live births, respectively. Thus, of the 211 participating patients, 107 carried their pregnancies to term, representing a cumulative live birth rate of 50.7%. No statistically significant differences between the use fresh and vitrified oocytes were found for any of the variables studied. CONCLUSIONS: Oocyte vitrification offered the possibility of gestation in more than one attempt after just one controlled hyperstimulation. Apart from alleviating the financial burden on patients, vitrification of oocytes may result in a feasible solution for the problems generated by abandoned frozen embryos. PMID- 27203093 TI - The Impact of Serum Progesterone Levels on the Results of In Vitro Fertilization Treatments: A Literature Review. AB - The aim of this review is to analyze the relationship between preovulatory progesterone (P) rise and in vitro fertilization (IVF) pregnancy outcomes. It also investigates the sources and effects of rises in progesterone levels, including the underlying mechanisms and potential strategies in preventing its elevation during ovarian stimulation. Progesterone is produced in the early follicular phase in the adrenal gland, which shifts toward the ovaries prior to ovulation. Several factors contribute to the etiology of P level increase including the number of multiple follicles, the overdose of gonadotropins and poor ovarian response. Nowadays, the influence of the preovulatory P rise on IVF outcome remains controversial. Several authors have failed to demonstrate any negative impact, while others reported a detrimental effect associated with the rise of P. It seems that P rise (1.5 ng/ml or 4.77 nmol/l) may have deleterious effects on endometrial receptivity, namely, accelerating the endometrial maturation process that subsequently narrows the period for implantation and thus decreases pregnancy rates. Recent studies have proposed different cutoffs according to the ovarian response, which may be a little high in patients with high response in relation to those of normal response or low response. To prevent a P rise, it might be preferable to use milder stimulation protocols, earlier trigger of ovulation, cryopreservation of all embryos and transfer in the natural cycle. PMID- 27203094 TI - Children Born by Assisted Fertilization: Information on the Procreative Origin. AB - This paper briefly reviews some aspects that affect people with infertility problems and children born through assisted reproduction techniques. Making a decision to have a child and accepting medical help represents an important moment in the life of a couple. All parents are confronted at some point, with the questions, that every child asks, that is: "How was I born?" All children need to know their origin. However, most parents are not comfortable providing the answer. In case of parents, who resorted to reproductive medicine, the answer requires a particular approach, mainly because it often revives painful and unresolved internal conflicts. Another problem is that parents do not feel comfortable to talk about the fact that medical help was required to conceive their child and that medical intervention sometimes requires the donation of gametes (eggs or sperm); or simply, they do not know how to talk to children about this issue. However, children have the right to know their origin. Our study indicates that some children with behavioral problems improved significantly after the family spoke openly about their origin. Children need to be told the truth. We cannot lie to them nor remain silent. PMID- 27203095 TI - Monozygotic Twin Pregnancy Associated with In Vitro Fertilization: Report and Revision of Three Cases Presented in a Clinic at 10,925 Feet Above Sea Level. AB - 3 cases of monozygotic twin pregnancies associated with IVF presented at Centro de Fertilidad y Ginecologia del Sur. In this study, we describe the cases and review the literature, noting possible related factors. PMID- 27203097 TI - Oral Presentations - Abstracts of the 19th Annual Congress of the SBRA, Buzios, RJ, 05-08 August 2015. PMID- 27203096 TI - Time-lapse Systems in Assisted Reproduction: The Importance of the Earliest Steps of Fertilization. PMID- 27203098 TI - Poster Presentations - Abstracts of the 19th Annual Congress of the SBRA, Buzios, RJ, 05-08 August 2015. PMID- 27203099 TI - Asynchronous Detected Disappearance of the Pro-nuclei by Time-Lapse X Embryonic Development. AB - OBJECTIVE: To investigate whether pro-nuclei disappearance synchronicity would have something to do with blastomere cleavage time up to D3 (timeline) and if it would be associated with the appearance of embryo abnormalities. METHODS: The sample of the present study was designed with 100 embryos (n = 100). With the aid of an embryonic analysis equipment: Time-Lapse, we studied embryonic morphokinetics from the zygote stage to D3. RESULTS: When there was no pronuclei synchronous disappearance, 30.8% underwent normal cleavage, whereas when there was pronuclei synchronous disappearance, 44.8% had normal cleavage. When there was no pronuclei synchronous disappearance, 46.2% had some type of abnormality, whereas when there was pronuclei synchronous disappearance, 56.3% had some kind of abnormality. CONCLUSION: Although the statistical results were not significant, we believe that with a larger sample size we could state with higher reliability, that the pro-nuclei synchronous disappearance analysis may, in the near future, indicate higher embryo quality. PMID- 27203100 TI - Converting Nonliquid Crystals into Liquid Crystals by N-Methylation in the Central Linker of Triazine-Based Dendrimers. AB - Two triazine-based dendrimers were successfully prepared in 60-75% yields. These newly prepared dendrimers 2a and 2b containing the -NMe(CH2)2NMe- and the NMe(CH2)4NMe- linkers between two G3 dendrons, respectively, exhibit columnar phases during the thermal process. However, the corresponding dendrimers 1a and 1b containing the -NH(CH2)2NH- and the -NH(CH2)4NH- linkers between two G3 dendrons, respectively, do not show any LC phases on thermal treatment. Computational investigations on molecular conformations reveal that N-methylation of the dendritic central linker leads dendrimers to possess more isomeric conformations and thus successfully converts non-LC dendrimers (1a and 1b) into LC dendrimers (2a and 2b). PMID- 27203101 TI - Publishing Science in the Time of Zika. PMID- 27203102 TI - Lack of Evidence that CYTH2/ARNO Functions as a Direct Intracellular EGFR Activator. PMID- 27203103 TI - PCSK9 Inhibitors. AB - Alirocumab and evolocumab are monoclonal antibodies that block proprotein convertase subtilisin/kexin type 9 (PCSK9), a circulating protein that degrades low-density lipoprotein (LDL) receptors. These therapies increase LDL receptors on the cell surface and reduce plasma LDL cholesterol. Both therapies are approved to lower LDL cholesterol, a causative agent for atherosclerotic cardiovascular disease. PMID- 27203104 TI - On a Quest for Principles, Big Data in Hand. AB - Cell editor Karen Carniol discusses the excitement and challenges of the "big data" era and how quantitative approaches reveal important biological principles with Galit Lahav, Gurol Suel, and Olga Troyanskaya. Annotated excerpts from this conversation are presented below, and the full conversation is available with the article online. PMID- 27203105 TI - iPSCs: 10 Years and Counting. PMID- 27203106 TI - Lessons from a Recovering Academic. AB - The conversion of basic biology into new therapeutics requires scientific activities in both academia and industry. Successful drug discovery projects span disciplines, sectors, and institutions and tightly couple laboratory and clinical experiments. Here, Ehlers describes conceptions and misconceptions about how science is conducted in industry versus academia. PMID- 27203107 TI - Tension-Time Integrals and Genetic Cardiomyopathy: The Force Is with You. AB - Hundreds of different mutations in genes encoding a few dozen sarcomeric proteins cause two reciprocal human disease phenotypes, hypertrophic or dilated cardiomyopathy. How molecular dysfunction evokes different patterns of cardiac remodeling is unclear. Davis et al. describe a biophysical metric of cardiomyocyte function, the force-time integral, which predicts disease phenotype. PMID- 27203108 TI - Swollen Nuclei Signal from the Grave. AB - Eicosanoid signaling plays key pro-inflammatory roles during tissue damage. Now, Enyedi et al. show that swelling of nuclei in cell corpses activates eicosanoid signaling to recruit leukocytes to sites of tissue damage. The enhanced membrane tension in swollen nuclei directly promotes calcium-dependent translocation and activation of enzymes involved in eicosanoid biosynthesis. PMID- 27203109 TI - Mitochondria: Masters of Epigenetics. AB - Accumulating evidence argues that aging exerts a profound influence on epigenetics, and vice versa. A pair of studies by Merkwirth et al. and Tian et al. now provide insights on how mitochondrial stress experienced by C. elegans larvae propagates a specific and persistent epigenetic response that protects adult cells and extends lifespan. PMID- 27203111 TI - Mechanisms and Consequences of Macromolecular Phase Separation. AB - Over a century ago, colloidal phase separation of matter into non-membranous bodies was recognized as a fundamental organizing principal of cell "protoplasm." Recent insights into the molecular properties of such phase-separated bodies present challenges to our understanding of cellular protein interaction networks, as well as opportunities for interpreting and understanding of native and pathological genetic and molecular interactions. Here, we briefly review examples of and discuss physical principles of phase-separated cellular bodies and then reflect on how knowledge of these principles may direct future research on their functions. PMID- 27203110 TI - The Structure and Dynamics of Higher-Order Assemblies: Amyloids, Signalosomes, and Granules. AB - We here attempt to achieve an integrated understanding of the structure and dynamics of a number of higher-order assemblies, including amyloids, various kinds of signalosomes, and cellular granules. We propose that the synergy between folded domains, linear motifs, and intrinsically disordered regions regulates the formation and intrinsic fuzziness of all higher-order assemblies, creating a structural and dynamic continuum. We describe how such regulatory mechanisms could be influenced under pathological conditions. PMID- 27203112 TI - The Cell Nucleus Serves as a Mechanotransducer of Tissue Damage-Induced Inflammation. AB - Tissue damage activates cytosolic phospholipase A2 (cPLA2), releasing arachidonic acid (AA), which is oxidized to proinflammatory eicosanoids by 5-lipoxygenase (5 LOX) on the nuclear envelope. How tissue damage is sensed to activate cPLA2 is unknown. We investigated this by live imaging in wounded zebrafish larvae, where damage of the fin tissue causes osmotic cell swelling at the wound margin and the generation of a chemotactic eicosanoid signal. Osmotic swelling of cells and their nuclei activates cPla2 by translocating it from the nucleoplasm to the nuclear envelope. Elevated cytosolic Ca(2+) was necessary but not sufficient for cPla2 translocation, and nuclear swelling was required in parallel. cPla2 translocation upon nuclear swelling was reconstituted in isolated nuclei and appears to be a simple physical process mediated by tension in the nuclear envelope. Our data suggest that the nucleus plays a mechanosensory role in inflammation by transducing cell swelling and lysis into proinflammatory eicosanoid signaling. PMID- 27203114 TI - Retraction Notice to: Cytohesins Are Cytoplasmic ErbB Receptor Activators. PMID- 27203115 TI - SnapShot: Microglia in Disease. AB - The development and maintenance of the central nervous system is dependent upon regulated, homeostatic actions of microglia, which sculpt and refine neuronal circuitry. By contrast, dysregulation of microglia contributes to the pathology of neurodevelopmental disorders such as autism spectrum disorders; neurodegenerative disorders such as Alzheimer's disease; and schizophrenia and chronic neuropathic pain. PMID- 27203113 TI - Cistrome and Epicistrome Features Shape the Regulatory DNA Landscape. AB - The cistrome is the complete set of transcription factor (TF) binding sites (cis elements) in an organism, while an epicistrome incorporates tissue-specific DNA chemical modifications and TF-specific chemical sensitivities into these binding profiles. Robust methods to construct comprehensive cistrome and epicistrome maps are critical for elucidating complex transcriptional networks that underlie growth, behavior, and disease. Here, we describe DNA affinity purification sequencing (DAP-seq), a high-throughput TF binding site discovery method that interrogates genomic DNA with in-vitro-expressed TFs. Using DAP-seq, we defined the Arabidopsis cistrome by resolving motifs and peaks for 529 TFs. Because genomic DNA used in DAP-seq retains 5-methylcytosines, we determined that >75% (248/327) of Arabidopsis TFs surveyed were methylation sensitive, a property that strongly impacts the epicistrome landscape. DAP-seq datasets also yielded insight into the biology and binding site architecture of numerous TFs, demonstrating the value of DAP-seq for cost-effective cistromic and epicistromic annotation in any organism. PMID- 27203116 TI - Programming Surface Chemistry with Engineered Cells. AB - We have developed synthetic gene networks that enable engineered cells to selectively program surface chemistry. E. coli were engineered to upregulate biotin synthase, and therefore biotin synthesis, upon biochemical induction. Additionally, two different functionalized surfaces were developed that utilized binding between biotin and streptavidin to regulate enzyme assembly on programmable surfaces. When combined, the interactions between engineered cells and surfaces demonstrated that synthetic biology can be used to engineer cells that selectively control and modify molecular assembly by exploiting surface chemistry. Our system is highly modular and has the potential to influence fields ranging from tissue engineering to drug development and delivery. PMID- 27203117 TI - Threshold for Terahertz Resonance of Nanoparticles in Water. AB - Nanoparticle vibrations are coupled to light through electrostriction, which gives nonlinear optical scattering. We investigated the acoustic response of 2 nm gold nanoparticles using a nearly degenerate four-wave mixing experimental configuration and show that the nonlinear response suddenly turns on at low powers (<100 mW) for continuous-wave (CW) lasers. The observed nonlinear response is a million times larger than typical electronic nonlinearities. The threshold implies a dramatic change in the quality factor of the vibrating nanoparticles, 4 orders of magnitude larger than usual hydrodynamic theory predicts. It is as if the water is removed altogether, which we speculate is the result of the vibrating particle pushing away the water molecules to form a stable cavity. Because these acoustic vibrations extend to terahertz frequencies, there is potential to harness this effect for high speed optical data processing, as well as to probe the dynamics of proteins all having acoustic modes in this range. PMID- 27203118 TI - Carrier Polarity Control in alpha-MoTe2 Schottky Junctions Based on Weak Fermi Level Pinning. AB - The polarity of the charge carriers injected through Schottky junctions of alpha phase molybdenum ditelluride (alpha-MoTe2) and various metals was characterized. We found that the Fermi-level pinning in the metal/alpha-MoTe2 Schottky junction is so weak that the polarity of the carriers (electron or hole) injected from the junction can be controlled by the work function of the metals, in contrast to other transition metal dichalcogenides such as MoS2. From the estimation of the Schottky barrier heights, we obtained p-type carrier (hole) injection from a Pt/alpha-MoTe2 junction with a Schottky barrier height of 40 meV at the valence band edge. n-Type carrier (electron) injection from Ti/alpha-MoTe2 and Ni/alpha MoTe2 junctions was also observed with Schottky barrier heights of 50 and 100 meV, respectively, at the conduction band edge. In addition, enhanced ambipolarity was demonstrated in a Pt-Ti hybrid contact with a unique structure specially designed for polarity-reversible transistors, in which Pt and Ti electrodes were placed in parallel for injecting both electrons and holes. PMID- 27203119 TI - Chemically Exfoliated SnSe Nanosheets and Their SnSe/Poly(3,4 ethylenedioxythiophene):Poly(styrenesulfonate) Composite Films for Polymer Based Thermoelectric Applications. AB - Tin selenide (SnSe) nanosheets (NSs) are prepared by hydrothermal lithium intercalation and a subsequent exfoliation process from a SnSe ingot. Conducting polymer poly(3,4-ethylenedioxythiohene):poly(styrenesulfonate) ( PEDOT: PSS) based thermoelectric composites are fabricated with varying SnSe NSs content, and the thermoelectric properties of the composites are examined at 300 K. The exfoliated SnSe particles show thin two-dimensional sheet-like structures that are evenly distributed into the PEDOT: PSS matrix. The significantly enhanced power factor (S(2).sigma) of the SnSe NS/PEDOT:PSS composites with increasing SnSe NSs content can be explained by the potential difference at the interface between the SnSe and PEDOT: PSS. The fabricated SnSe NS/PEDOT:PSS composites show a maximum figure of merit (ZT) of 0.32 at a SnSe NSs loading of 20 wt %. The mixing of inorganic nanoparticles with the conducting polymer matrix forms products with extremely low thermal conductivities, which is a promising strategy for the realization of polymer based efficient thermoelectric applications. PMID- 27203120 TI - Axial Chirality about Boron-Carbon Bond: Atropisomeric Azaborines. AB - The preparation of atropisomeric 2,1-borazaronaphthalenes is described. Resolution of the atropisomeric pair was achieved by preparative Chiral Stationary Phase HPLC (CSP-HPLC). The absolute configuration of the stereogenic axis was derived from Time-Dependent DFT (TD-DFT) simulation of the Electronic Circular Dichroism spectra (ECD). X-ray diffraction and Dynamic NMR data allowed structural and dynamic comparison with the analogue isosteric carbon compounds. PMID- 27203125 TI - Numerical Simulation of Permeability Change in Wellbore Cement Fractures after Geomechanical Stress and Geochemical Reactions Using X-ray Computed Tomography Imaging. AB - X-ray microtomography (XMT) imaging combined with three-dimensional (3D) computational fluid dynamics (CFD) modeling technique was used to study the effect of geochemical and geomechanical processes on fracture permeability in composite Portland cement-basalt caprock core samples. The effect of fluid density and viscosity and two different pressure gradient conditions on fracture permeability was numerically studied by using fluids with varying density and viscosity and simulating two different pressure gradient conditions. After the application of geomechanical stress but before CO2-reaction, CFD revealed fluid flow increase, which resulted in increased fracture permeability. After CO2 reaction, XMT images displayed preferential precipitation of calcium carbonate within the fractures in the cement matrix and less precipitation in fractures located at the cement-basalt interface. CFD estimated changes in flow profile and differences in absolute values of flow velocity due to different pressure gradients. CFD was able to highlight the profound effect of fluid viscosity on velocity profile and fracture permeability. This study demonstrates the applicability of XMT imaging and CFD as powerful tools for characterizing the hydraulic properties of fractures in a number of applications like geologic carbon sequestration and storage, hydraulic fracturing for shale gas production, and enhanced geothermal systems. PMID- 27203127 TI - Dosimetric comparisons of carbon ion treatment plans for 1D and 2D ripple filters with variable thicknesses. AB - A ripple filter (RiFi)-also called mini-ridge filter-is a passive energy modulator used in particle beam treatments that broadens the Bragg peak (BP) as a function of its maximum thickness. The number of different energies requested from the accelerator can thus be reduced, which significantly reduces the treatment time. A new second generation RiFi with 2D groove shapes was developed using rapid prototyping, which optimizes the beam-modulating material and enables RiFi thicknesses of up to 6 mm. Carbon ion treatment plans were calculated using the standard 1D 3 mm thick RiFi and the new 4 and 6 mm 2D RiFis for spherical planning target volumes (PTVs) in water, eight stage I non-small cell lung cancer cases, four skull base chordoma cases and three prostate cancer cases. TRiP98 was used for treatment planning with facility-specific base data calculated with the Monte Carlo code SHIELD-HIT12A. Dose-volume-histograms, spatial dose distributions and dosimetric indexes were used for plan evaluation. Plan homogeneity and conformity of thinner RiFis were slightly superior to thicker RiFis but satisfactory results were obtained for all RiFis investigated. For the 6 mm RiFi, fine structures in the dose distribution caused by the larger energy steps were observed at the PTV edges, in particular for superficial and/or very small PTVs but performances for all RiFis increased with penetration depth due to straggling and scattering effects. Plans with the new RiFi design yielded for the studied cases comparable dosimetric results to the standard RiFi while the 4 and 6 mm RiFis lowered the irradiation time by 25-30% and 45-49%, respectively. PMID- 27203126 TI - Mechanism for Six-Electron Aryl-N-Oxygenation by the Non-Heme Diiron Enzyme CmlI. AB - The ultimate step in chloramphenicol (CAM) biosynthesis is a six-electron oxidation of an aryl-amine precursor (NH2-CAM) to the aryl-nitro group of CAM catalyzed by the non-heme diiron cluster-containing oxygenase CmlI. Upon exposure of the diferrous cluster to O2, CmlI forms a long-lived peroxo intermediate, P, which reacts with NH2-CAM to form CAM. Since P is capable of at most a two electron oxidation, the overall reaction must occur in several steps. It is unknown whether P is the oxidant in each step or whether another oxidizing species participates in the reaction. Mass spectrometry product analysis of reactions under (18)O2 show that both oxygen atoms in the nitro function of CAM derive from O2. However, when the single-turnover reaction between (18)O2-P and NH2-CAM is carried out in an (16)O2 atmosphere, CAM nitro groups contain both (18)O and (16)O, suggesting that P can be reformed during the reaction sequence. Such reformation would require reduction by a pathway intermediate, shown here to be NH(OH)-CAM. Accordingly, the aerobic reaction of NH(OH)-CAM with diferric CmlI yields P and then CAM without an external reductant. A catalytic cycle is proposed in which NH2-CAM reacts with P to form NH(OH)-CAM and diferric CmlI. Then the NH(OH)-CAM rereduces the enzyme diiron cluster, allowing P to reform upon O2 binding, while itself being oxidized to NO-CAM. Finally, the reformed P oxidizes NO-CAM to CAM with incorporation of a second O2-derived oxygen atom. The complete six-electron oxidation requires only two exogenous electrons and could occur in one active site. PMID- 27203128 TI - Li Intercalation into Graphite: Direct Optical Imaging and Cahn-Hilliard Reaction Dynamics. AB - Lithium intercalation into graphite is a critical process in energy storage technology. Studies of Li intercalation kinetics have proved challenging due to structural and phase complexity, and sample heterogeneity. Here we report direct time- and space-resolved, all-optical measurement of Li intercalation. We use a single crystal graphite electrode with lithographically defined disc geometry. All-optical, Raman and reflectance measurements distinguish the intrinsic intercalation process from side reactions, and provide new insight into the microscopic intercalation process. The recently proposed Cahn-Hilliard reaction (CHR) theory quantitatively captures the observed phase front spatial patterns and dynamics, using a two-layer free-energy model with novel, generalized Butler Volmer kinetics. This approach unites Cahn-Hilliard and electrochemical kinetics, using a thermodynamically consistent description of the Li injection reaction at the crystal edge that involves a cooperative opening of graphene planes. The excellent agreement between experiment and theory presented here, with single crystal resolution, provides strong support for the CHR theory of solid-state reactions. PMID- 27203129 TI - Role of spatial averaging in multicellular gradient sensing. AB - Gradient sensing underlies important biological processes including morphogenesis, polarization, and cell migration. The precision of gradient sensing increases with the length of a detector (a cell or group of cells) in the gradient direction, since a longer detector spans a larger range of concentration values. Intuition from studies of concentration sensing suggests that precision should also increase with detector length in the direction transverse to the gradient, since then spatial averaging should reduce the noise. However, here we show that, unlike for concentration sensing, the precision of gradient sensing decreases with transverse length for the simplest gradient sensing model, local excitation-global inhibition. The reason is that gradient sensing ultimately relies on a subtraction of measured concentration values. While spatial averaging indeed reduces the noise in these measurements, which increases precision, it also reduces the covariance between the measurements, which results in the net decrease in precision. We demonstrate how a recently introduced gradient sensing mechanism, regional excitation-global inhibition (REGI), overcomes this effect and recovers the benefit of transverse averaging. Using a REGI-based model, we compute the optimal two- and three-dimensional detector shapes, and argue that they are consistent with the shapes of naturally occurring gradient-sensing cell populations. PMID- 27203130 TI - The Incidence of Trocar Site Hernia After Single-Port Laparoscopic Cholecystectomy-A Single Center Analysis and Literature Review. AB - BACKGROUND: Single-port laparoscopic cholecystectomy (SLC) requires a larger initial umbilical incision than conventional multiport laparoscopic cholecystectomy (MLC). In this retrospective analysis study we compared the demographics, clinical data, and incidence of postoperative trocar site hernias (TSH) in patients undergoing SLC with those in patients undergoing MLC. PATIENTS AND METHODS: A total of 161 patients were included in this study. Of these patients, 104 underwent MLC, 57 SLC. Patients in the MLC group were operated on using the four-trocar technique, patients in the SLC-port group using a fully reusable multi-trocar port system (X-ConeTM). The earliest follow-up point was 12 months, the average follow-up period was 16.4 months (range 12-24 mos). The follow-up examinations for all patients consisted of a review of their medical history, a thorough physical examination, and an ultrasound examination of all existing trocar site scars. RESULTS: Patients in the SLC group had a lower mean American Society of Anesthesiologists score and a lower mean body mass index compared to patients in the MLC group. The average operating time was shorter for the patients in the SLC group, but the difference was not statistically significant. Ten (9.6%) patients in the MLC group and 3 (5.3%) in the SLC group developed a TSH (p = .55). CONCLUSIONS: At midterm follow-up the incidence of umbilical incisional hernias was not greater for SLC compared to MLC. The incidence of TSH after MLC was significantly higher than expected. PMID- 27203131 TI - Reducing Emergency Department Visits for Acute Gastrointestinal Illnesses in North Carolina (USA) by Extending Community Water Service. AB - BACKGROUND: Previous analyses have suggested that unregulated private drinking water wells carry a higher risk of exposure to microbial contamination than regulated community water systems. In North Carolina, ~35% of the state's population relies on private wells, but the health impact associated with widespread reliance on such unregulated drinking water sources is unknown. OBJECTIVES: We estimated the total number of emergency department visits for acute gastrointestinal illness (AGI) attributable to microbial contamination in private wells in North Carolina per year, the costs of those visits, and the potential health benefits of extending regulated water service to households currently relying on private wells for their drinking water. METHODS: We developed a population intervention model using 2007-2013 data from all 122 North Carolina emergency departments along with microbial contamination data for all 2,120 community water systems and for 16,138 private well water samples collected since 2008. RESULTS: An estimated 29,400 (95% CI: 26,600, 32,200) emergency department visits per year for acute gastrointestinal illness were attributable to microbial contamination in drinking water, constituting approximately 7.3% (95% CI: 6.6, 7.9%) of all AGI-related visits. Of these attributable cases, 99% (29,200; 95% CI: 26,500, 31,900) were associated with private well contamination. The estimated statewide annual cost of emergency department visits attributable to microbiological contamination of drinking water is 40.2 million USD (95% CI: 2.58 million USD, 193 million USD), of which 39.9 million USD (95% CI: 2.56 million USD, 192 million USD) is estimated to arise from private well contamination. An estimated 2,920 (95% CI: 2,650, 3,190) annual emergency department visits could be prevented by extending community water service to 10% of the population currently relying on private wells. CONCLUSIONS: This research provides new evidence that extending regulated community water service to populations currently relying on private wells may decrease the population burden of acute gastrointestinal illness. CITATION: DeFelice NB, Johnston JE, Gibson JM. 2016. Reducing emergency department visits for acute gastrointestinal illnesses in North Carolina (USA) by extending community water service. Environ Health Perspect 124:1583-1591; http://dx.doi.org/10.1289/EHP160. PMID- 27203132 TI - Assessment of 25 CYP2D6 alleles found in the Chinese population on propafenone metabolism in vitro. AB - Cytochrome P450 enzyme 2D6 (CYP2D6) is an important member of the cytochrome P450 enzyme superfamily, with more than 100 CYP2D6 allelic variants being previously reported. The aim of this study was to assess the catalytic characteristics of 25 alleles (CYP2D6.1 and 24 CYP2D6 variants) and their effects on the metabolism of propafenone in vitro. Twenty-five CYP2D6 alleles were expressing in 21 Spodoptera frugiperda (Sf) insect cells, and each variant was evaluated using propafenone as the substrate. Reactions were performed at 37 degrees C with 1-100 MUmol/L propafenone for 30 min. After termination, the product 5-OH-propafenone was extracted and used for signal collection by ultra-performance liquid chromatography (UPLC). Compared with wild type CYP2D6.1, the intrinsic clearance (Vmax and Km) values of all variants were significantly altered. Three variants (CYP2D6.87, CYP2D6.90, CYP2D6.F219S) exhibited markedly increased intrinsic clearance values (129% to 165%), whereas 21 variants exhibited significantly decreased values (16% to 85%) due to increased Km and (or) decreased Vmax values. These results indicated that the majority of tested alleles had significantly altered catalytic activity towards propafenone hydroxylation in this expression system. Attention should be paid to subjects carrying these rare alleles when treated with propafenone. PMID- 27203133 TI - Human biomarkers: can they help us to develop a new tuberculosis vaccine? AB - The most effective intervention for the control of infectious disease is vaccination. The BCG vaccine, the only licensed vaccine for the prevention of tuberculosis (TB) disease, is only partially effective and a new vaccine is urgently needed. Biomarkers can aid the development of new TB vaccines through discovery of immune mechanisms, early assessment of vaccine immunogenicity or vaccine take and identification of those at greatest risk of disease progression for recruitment into smaller, targeted efficacy trials. The ultimate goal, however, remains a biomarker of TB vaccine efficacy that can be used as a surrogate for a TB disease end point and there remains an urgent need for further research in this area. PMID- 27203135 TI - A physical framework for implementing virtual models of intracranial pressure and cerebrospinal fluid dynamics in hydrocephalus shunt testing. AB - OBJECTIVE The surgical placement of a shunt designed to resolve the brain's impaired ability to drain excess CSF is one of the most common treatments for hydrocephalus. The use of a dynamic testing platform is an important part of shunt testing that can faithfully reproduce the physiological environment of the implanted shunts. METHODS A simulation-based framework that serves as a proof of concept for enabling the application of virtual intracranial pressure (ICP) and CSF models to a physical shunt-testing system was engineered. This was achieved by designing hardware and software that enabled the application of dynamic model driven inlet and outlet pressures to a shunt and the subsequent measurement of the resulting drainage rate. RESULTS A set of common physiological scenarios was simulated, including oscillations in ICP due to respiratory and cardiac cycles, changes in baseline ICP due to changes in patient posture, and transient ICP spikes caused by activities such as exercise, coughing, sneezing, and the Valsalva maneuver. The behavior of the Strata valve under a few of these physiological conditions is also demonstrated. CONCLUSIONS Testing shunts with dynamic ICP and CSF simulations can facilitate the optimization of shunts to be more failure resistant and better suited to patient physiology. PMID- 27203134 TI - Diffusion tensor imaging study of pediatric patients with congenital hydrocephalus: 1-year postsurgical outcomes. AB - OBJECTIVE The purpose of this study was to investigate white matter (WM) structural abnormalities using diffusion tensor imaging (DTI) in children with hydrocephalus before CSF diversionary surgery (including ventriculoperitoneal shunt insertion and endoscopic third ventriculostomy) and during the course of recovery after surgery in association with neuropsychological and behavioral outcome. METHODS This prospective study included 54 pediatric patients with congenital hydrocephalus (21 female, 33 male; age range 0.03-194.5 months) who underwent surgery and 64 normal controls (30 female, 34 male; age range 0.30 197.75 months). DTI and neurodevelopmental outcome data were collected once in the control group and 3 times (preoperatively and at 3 and 12 months postoperatively) in the patients with hydrocephalus. DTI measures, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) values were extracted from the genu of the corpus callosum (gCC) and the posterior limb of internal capsule (PLIC). Group analysis was performed first cross-sectionally to quantify DTI abnormalities at 3 time points by comparing the data obtained in the hydrocephalus group for each of the 3 time points to data obtained in the controls. Longitudinal comparisons were conducted pairwise between different time points in patients whose data were acquired at multiple time points. Neurodevelopmental data were collected and analyzed using the Adaptive Behavior Assessment System, Second Edition, and the Bayley Scales of Infant Development, Third Edition. Correlation analyses were performed between DTI and behavioral measures. RESULTS Significant DTI abnormalities were found in the hydrocephalus patients in both the gCC (lower FA and higher MD, AD, and RD) and the PLIC (higher FA, lower AD and RD) before surgery. The DTI measures in the gCC remained mostly abnormal at 3 and 12 months after surgery. The DTI abnormalities in the PLIC were significant in FA and AD at 3 months after surgery but did not persist when tested at 12 months after surgery. Significant longitudinal DTI changes in the patients with hydrocephalus were found in the gCC when findings at 3 and 12 months after surgery were compared. In the PLIC, trend-level longitudinal changes were observed between preoperative findings and 3-month postoperative findings, as well as between 3- and 12-month postoperative findings. Significant correlation between DTI and developmental outcome was found at all 3 time points. Notably, a significant correlation was found between DTI in the PLIC at 3 months after surgery and developmental outcome at 12 months after surgery. CONCLUSIONS The data showed significant WM abnormality based on DTI in both the gCC and the PLIC in patients with congenital hydrocephalus before surgery, and the abnormalities persisted in both the gCC and the PLIC at 3 months after surgery. The DTI values remained significantly abnormal in the gCC at 12 months after surgery. Longitudinal analysis showed signs of recovery in both WM structures between different time points. Combined with the significant correlation found between DTI and neuropsychological measures, the findings of this study suggest that DTI can serve as a sensitive imaging biomarker for underlying neuroanatomical changes and postsurgical developmental outcome and even as a predictor for future outcomes. PMID- 27203136 TI - Outcomes of endoscopic suturectomy with postoperative helmet therapy in bilateral coronal craniosynostosis. AB - OBJECTIVE Historically, bilateral frontoorbital advancement (FOA) has been the keystone for treatment of turribrachycephaly caused by bilateral coronal synostosis. Early endoscopic suturectomy has become a popular technique for treatment of single-suture synostosis, with acceptable results and minimal perioperative morbidity. Boston Children's Hospital has adopted this method of treating early-presenting cases of bilateral coronal synostosis. METHODS A retrospective review of patients with bilateral coronal craniosynostosis who were treated with endoscopic suturectomy between 2005 and 2012 was completed. Patients were operated on between 1 and 4 months of age. Hospital records were reviewed for perioperative morbidity, length of stay, head circumference and cephalic indices, and the need for further surgery. RESULTS Eighteen patients were identified, 8 males and 10 females, with a mean age at surgery of 2.6 months (range 1-4 months). Nine patients had syndromic craniosynostosis. The mean duration of surgery was 73.3 minutes (range 50-93 minutes). The mean blood loss was 40 ml (range 20-100 ml), and 2 patients needed a blood transfusion. The mean duration of hospital stay was 1.2 days (range 1-2 days). There was 1 major complication in the form of a CSF leak. The mean follow-up was 37 months (range 6 102 months). Eleven percent of nonsyndromic patients required a subsequent FOA; 55.6% of syndromic patients underwent FOA. The head circumference percentiles and cephalic indices improved significantly. CONCLUSIONS Early endoscopic suturectomy successfully treats the majority of patients with bilateral coronal synostosis, and affords a short procedure time, a brief hospital stay, and an expedited recovery. Close follow-up is needed to detect patients who will require a secondary FOA due to progressive suture fusion or resynostosis of the released coronal sutures. PMID- 27203139 TI - Body habitus, serum albumin, and the outcomes after craniotomy for tumor: a National Surgical Quality Improvement Program analysis. AB - OBJECTIVE Although there is a growing body of research highlighting the negative impact of obesity and malnutrition on surgical outcomes, few studies have evaluated these parameters in patients undergoing intracranial surgery. The goal of this study was to use a national registry to evaluate the association of body mass index (BMI) and hypoalbuminemia with 30-day outcomes after craniotomy for tumor. METHODS Adult patients who underwent craniotomy for tumor were extracted from the prospective National Surgical Quality Improvement Program registry. Patients were stratified by body habitus according to the WHO classification, as well as by preoperative hypoalbuminemia (< 3.5 g/dl). Multivariable logistic regression evaluated the association of body habitus and hypoalbuminemia with 30 day mortality, complications, and discharge disposition. Covariates included patient age, sex, race or ethnicity, tumor histology, American Society of Anesthesiology class, preoperative functional status, comorbidities (including hypertension and diabetes mellitus), and additional preoperative laboratory values. RESULTS Among the 11,510 patients included, 28.7% were classified as normal weight (BMI 18.5-24.9 kg/m2), 1.9% as underweight (BMI < 18.5 kg/m2), 33.4% as overweight (BMI 25.0-29.9 kg/m2), 19.1% as Class I obese (BMI 30.0-34.9 kg/m2), 8.3% as Class II obese (BMI 35.0-39.9 kg/m2), 5.5% as Class III obese (BMI >= 40.0 kg/m2), and 3.1% had missing BMI data. In multivariable regression models, body habitus was not associated with differential odds of mortality, postoperative stroke or coma, or a nonroutine hospital discharge. However, the adjusted odds of a major complication were significantly higher for Class I obese (OR 1.28, 99% CI 1.01-1.62; p = 0.008), Class II obese (OR 1.53, 99% CI 1.13 2.07; p < 0.001), and Class III obese (OR 1.67, 99% CI 1.19-2.36; p < 0.001) patients compared with those of normal weight; a dose-dependent effect was seen, with increased effect size with greater adiposity. The higher odds of major complications was primarily due to significantly increased odds of a venous thromboembolism in overweight and obese patients, as well as of a surgical site infection in those with Class II or III obesity. Additionally, 41.0% of patients had an albumin level >= 3.5 g/dl, 9.6% had hypoalbuminemia, and 49.4% had a missing albumin value. Hypoalbuminemia was associated with significantly higher odds of mortality (OR 1.91, 95% CI 1.41-2.60; p < 0.001) or a nonroutine hospital discharge (OR 1.46, 95% CI 1.21-1.76; p < 0.001). CONCLUSIONS In this National Surgical Quality Improvement Program analysis evaluating patients who underwent craniotomy for tumor, body habitus was not associated with differential mortality or neurological complications. However, obese patients had increased odds of a major perioperative complication, primarily due to higher rates of venous thromboembolic events and surgical site infections. Preoperative hypoalbuminemia was associated with increased odds of mortality and a nonroutine hospital discharge, suggesting that serum albumin may have utility in stratifying risk preoperatively in patients undergoing craniotomy. PMID- 27203138 TI - Medicare expenditures for elderly patients undergoing surgical clipping or endovascular intervention for subarachnoid hemorrhage. AB - OBJECTIVE The impact of treatment method-surgical clipping or endovascular coiling-on the cost of care for patients with aneurysmal subarachnoid hemorrhage (SAH) is debated. Here, the authors investigated the association between treatment method and long-term Medicare expenditures in elderly patients with aneurysmal SAH. METHODS The authors performed a cohort study of 100% of the Medicare fee-for-service claims data for elderly patients who had undergone treatment for ruptured cerebral aneurysms in the period from 2007 to 2012. To control for measured confounding, the authors used propensity score-adjusted multivariable regression analysis with mixed effects to account for clustering at the hospital referral region (HRR) level. An instrumental variable (regional rates of coiling) analysis was used to control for unmeasured confounding by creating pseudo-randomization on the treatment method. RESULTS During the study period, 3210 patients underwent treatment for ruptured cerebral aneurysms and met the inclusion criteria. Of these patients, 1206 (37.6%) had surgical clipping and 2004 (62.4%) had endovascular coiling. The median total Medicare expenditures in the 1st year after admission for SAH were $113,000 (IQR $77,500-$182,000) for surgical clipping and $103,000 (IQR $72,900-$159,000) for endovascular coiling. When the authors adjusted for unmeasured confounders by using an instrumental variable analysis, clipping was associated with increased 1-year Medicare expenditures by $19,577 (95% CI $4492-$34,663). CONCLUSIONS In a cohort of Medicare patients with aneurysmal SAH, after controlling for unmeasured confounding, surgical clipping was associated with increased 1-year expenditures in comparison with endovascular coiling. PMID- 27203140 TI - Early diffusion-weighted MRI lesions after treatment of unruptured intracranial aneurysms: a prospective study. AB - OBJECTIVE Diffusion-weighted MRI was used to assess periprocedural lesion load after repair of unruptured intracranial aneurysms (UIA) by microsurgical clipping (MC) and endovascular coiling (EC). METHODS Patients with UIA were assigned to undergo MC or EC according to interdisciplinary consensus and underwent diffusion weighted imaging (DWI) 1 day before and 1 day after aneurysm treatment. Newly detected lesions by DWI after treatment were the primary end point of this prospective study. Lesions detected by DWI were categorized as follows: A) 1-3 DWI spots < 10 mm, B) > 3 DWI spots < 10 mm, C) single DWI lesion > 10 mm, or D) DWI lesion related to surgical access. RESULTS Between 2010 and 2014, 99 cases were included. Sixty-two UIA were treated by MC and 37 by EC. There were no significant differences between groups in age, sex, aneurysm size, occurrence of multiple aneurysms in 1 patient, or presence of lesions detected by DWI before treatment. Aneurysms treated by EC were significantly more often located in the posterior circulation (p < 0.001). Diffusion-weighted MRI detected new lesions in 27 (43.5%) and 20 (54.1%) patients after MC and EC, respectively (not significant). The pattern of lesions detected by DWI varied significantly between groups (p < 0.001). Microembolic lesions (A and B) found on DWI were detected more frequently after EC (A, 14 cases; B, 5 cases) than after MC (A, 5 cases), whereas C and D were rare after EC (C, 1 case) and occurred more often after MC (C, 12 cases and D, 10 cases). No procedure-related unfavorable outcomes were detected. CONCLUSIONS According to the specific techniques, lesion patterns differ between MC and EC, whereas the frequency of new lesions found on DWI is similar after occlusion of UIA. In general, the lesion load was low in both groups, and lesions were clinically silent. Clinical trial registration no.: NCT01490463 ( clinicaltrials.gov ). PMID- 27203141 TI - Role of terminal and anastomotic circulation in the patency of arteries jailed by flow-diverting stents: from hemodynamic changes to ostia surface modifications. AB - OBJECTIVE The outcome for jailing arterial branches that emerge near intracranial aneurysms during flow-diverting stent (FDS) deployment remains controversial. In this animal study, the authors aimed to elucidate the role of collateral supply with regard to the hemodynamic changes and neointimal modifications that occur from jailing arteries with FDSs. To serve this purpose, the authors sought to quantify 1) the hemodynamic changes that occur at the jailed arterial branches immediately after stent placement and 2) the ostia surface values at 3 months after stenting; both parameters were investigated in the presence or absence of collateral arterial flow. METHODS After an a priori power analysis, 2 groups (Group A and Group B) were created according to an animal flow model for terminal and anastomotic arterial circulation; each group contained 7 Large White swine. Group A animals possessed an anastomotic-type arterial configuration to supply the territory of the right ascending pharyngeal artery (APhA), while Group B animals possessed a terminal-type arterial configuration to supply the right APhA territory. Subsequently, all animals underwent FDS placement, thereby jailing the right APhAs. Mean flow rates and velocities inside the jailed branches were quantified using time-resolved 3D phase-contrast MR angiography before and after stenting. Three months after stent placement, the jailed ostia surface values were quantified on scanning electron micrographs. The data were analyzed using descriptive statistics and group comparisons with parametric and nonparametric tests. RESULTS The endovascular procedures were feasible, and there were no findings of in situ thrombus formation on postprocedural optical coherence tomography or ischemia on postprocedural diffusion-weighted imaging. In Group A, the mean flow rate values at the jailed right APhAs were reduced immediately following stent placement as compared with values obtained before stent placement (p = 0.02, power: 0.8). In contrast, the mean poststenting flow rates for Group B remained similar to those obtained before stent placement. Three months after stent placement, the mean ostia surface values were significantly higher for Group B (527,911 +/- 306,229 MUm2) than for Group A (89,329 +/- 59,762 MUm2; p < 0.01, power: 1.00), even though the initial dimensions of the jailed ostia were similar between groups. A statistically significant correlation was found between groups (A or B), mean flow rates after stent placement, and ostia surface values at 3 months. CONCLUSIONS When an important collateral supply was present, the jailing of side arteries with flow diverters resulted in an immediate and significant reduction in the flow rate inside these arteries as compared with the prestenting values. In contrast, when competitive flow was absent, jailing did not result in significant flow rate reductions inside the jailed arteries. Ostium surface values at 3 months after stent placement were significantly higher in the terminal group of jailed arteries (Group B) than in the anastomotic group (Group A) and strongly correlated with poststenting reductions in the velocity value. PMID- 27203142 TI - Primary versus revision transsphenoidal resection for nonfunctioning pituitary macroadenomas: matched cohort study. AB - OBJECTIVE The object of this study was to compare the outcomes of primary and revision transsphenoidal resection (TSR) of nonfunctioning pituitary macroadenomas (NFPMAs) using endoscopic methods. METHODS The authors retrospectively reviewed the records of 287 consecutive patients who had undergone endoscopic endonasal TSR for NFPMAs at their institution in the period from 2005 to 2011. Fifty patients who had undergone revision TSR were retrospectively matched for age, sex, and duration of follow-up to 46 patients who had undergone primary TSR. Medical and surgical complications were documented, and Kaplan-Meier analysis was performed to assess rates of radiological progression-free survival (PFS). RESULTS The median follow-up periods were 45 and 46 months for the primary and revision TSR groups, respectively. There were no significant differences between the primary and revision groups in rates of new neurological deficit (0 in each), vascular injury (2% vs 0), postoperative CSF leak (6% vs 2%), transient diabetes insipidus (DI; 15% vs 12%), chronic DI (2% vs 2%), chronic sinusitis (4% vs 6%), meningitis (2% vs 2%), epistaxis (7% vs 0), or suprasellar hematoma formation (0 vs 2%). However, patients who underwent primary TSR had significantly higher rates of syndrome of inappropriate antidiuretic hormone (SIADH; 17% vs 4%, p = 0.04). Patients who underwent primary operations also had significantly higher rates of gross-total resection (GTR; 63% vs 28%, p < 0.01) and significantly lower rates of adjuvant radiotherapy (13% vs 42%, p < 0.01). Radiological PFS rates were similar at 2 years (98% vs 96%) and 5 years (87% vs 80%, p = 0.668, log-rank test). CONCLUSIONS Patients who underwent primary TSR of NFPMAs experienced higher rates of SIADH than those who underwent revision TSR. Patients who underwent revision TSR were less likely to have GTR of their tumor, although they still had a PFS rate similar to that in patients who underwent primary TSR. This finding may be attributable to an increased rate of adjuvant radiation treatment to subtotally resected tumors in the revision TSR group. PMID- 27203143 TI - Hemorrhage from cerebral cavernous malformations: a systematic pooled analysis. AB - OBJECTIVE The aim of this paper is to define an overall cavernous malformation (CM) hemorrhage rate and risk factors for hemorrhage. METHODS The authors performed a systematic, pooled analysis via the PubMed database through October 2015 using the terms "cavernoma," "cavernous malformation," "natural history," "bleeding," and "hemorrhage." English-language studies providing annual rates and/or risk factors for CM hemorrhage were included. Data extraction, performed independently by the authors, included demographic data, hemorrhage rates, and hemorrhage risk factors. RESULTS Across 12 natural history studies with 1610 patients, the mean age at presentation was 42.7 years old and 52% of patients (95% CI 49%-55%) were female. Presentation modality was seizure in 30% (95% CI 25%-35%), hemorrhage in 26% (95% CI 17%-37%), incidental in 17% (95% CI 9%-31%), and focal deficits only in 16% of cases (95% CI 11%-23%). CM location was lobar in 66% (95% CI 61%-70%), brainstem in 18% (95% CI 13%-24%), deep supratentorial in 8% (95% CI 6%-10%), and cerebellar in 8% (95% CI 5%-11%). Pooling 7 studies that did not assume CM presence since birth, the annual hemorrhage rate was 2.5% per patient-year over 5081.2 patient-years of follow-up (95% CI 1.3%-5.1%). Pooling hazard ratios across 5 studies that evaluated hemorrhage risk factors, prior CM hemorrhage was a significant risk factor for hemorrhage (HR 3.73, 95% CI 1.26-11.1; p = 0.02) while younger age, female sex, deep location, size, multiplicity, and associated developmental venous anomalies (DVAs) were not. CONCLUSIONS Although limited by the heterogeneity of incorporated reports and selection bias, this study found prior hemorrhage to be a significant risk factor for CM bleeding, while age, sex, CM location, size, multiplicity, and associated DVAs were not. Future natural history studies should compound annual hemorrhage rate with prospective seizure and nonhemorrhagic neurological deficit rates. PMID- 27203144 TI - Letter to the Editor: Trigeminal neuralgia in patients with multiple sclerosis. PMID- 27203145 TI - Cortical plasticity catalyzed by prehabilitation enables extensive resection of brain tumors in eloquent areas. AB - OBJECTIVE The extent of resection is the most important prognostic factor following brain glioma surgery. However, eloquent areas within tumors limit the extent of resection and, thus, critically affect outcomes. The authors hypothesized that presurgical suppression of the eloquent areas within a tumor by continuous cortical electrical stimulation, coupled with appropriate behavioral training ("prehabilitation"), would induce plastic reorganization and enable a more extensive resection. METHODS The authors report on 5 patients harboring gliomas involving eloquent brain areas within tumors as identified on intraoperative stimulation mapping. A grid of electrodes was placed over the residual tumor, and continuous cortical electrical stimulation was targeted to the functional areas. The stimulation intensity was adjusted daily to provoke a mild functional impairment while the function was intensively trained. RESULTS The stimulation intensity required to impair function increased progressively in all patients, and all underwent another operation a mean of 33.6 days later (range 27-37 days), when the maximal stimulation voltage in all active contacts induced no functional deficit. In all cases, a substantially more extensive resection of the tumor was possible. Intraoperative mapping and functional MRI demonstrated a plastic reorganization, and most previously demonstrated eloquent areas within the tumor were silent, while there was new functional activation of brain areas in the same region or toward the contralateral hemisphere. CONCLUSIONS Prehabilitation with continuous cortical electrical stimulation and appropriate behavioral training prior to surgery in patients with WHO Grade II and III gliomas affecting eloquent areas accelerate plastic changes. This can help maximize tumor resection and, thus, improve survival while maintaining function. PMID- 27203146 TI - Microvascular decompression for tinnitus: systematic review. AB - OBJECTIVE The objective of this study was to examine operative outcomes in cases of microvascular decompression (MVD) of cranial nerve (CN) VIII for tinnitus through a critical review of the literature. METHODS Forty-three English-language articles were gathered from PubMed and analyzed. In this review, two different case types were distinguished: 1) tinnitus-only symptomatology, which was defined as a patient with tinnitus with or without sensorineural hearing loss; and 2) mixed symptomatology, which was defined as tinnitus with symptoms of other CN dysfunction. This review reports outcomes of those with tinnitus-only symptoms. RESULTS Forty-three tinnitus-only cases were found in the literature with a 60% positive outcome rate following MVD. Analysis revealed a 5-year cutoff of preoperative symptom duration before which a good outcome can be predicted with 78.6% sensitivity, and after which a poor outcome can be predicted with 80% specificity. CONCLUSIONS As the 60% success rate is more promising than several other therapeutic options open to the chronic tinnitus sufferer, future research into this field is warranted. PMID- 27203147 TI - Bipolar radiofrequency ablation of aneurysm remnants after coil embolization can improve endovascular treatment of experimental bifurcation aneurysms. AB - OBJECTIVE Endovascular treatment of aneurysms may result in incomplete initial occlusion and aneurysm recurrence at angiographic follow-up studies. This study aimed to assess the feasibility and efficacy of bipolar radiofrequency ablation (RFA) of aneurysm remnants after coil embolization. METHODS Bipolar RFA was accomplished using the coil mass as 1 electrode, while the second electrode was a stent placed across the aneurysmal neck. After preliminary experiments and protocol approval from the Animal Care committee, wide-necked bifurcation aneurysms were constructed in 24 animals. Aneurysms were allocated to 1 of 3 groups: partial intraoperative coil embolization, followed by RFA (n = 12; treated group) or without RFA (n = 6; control group 1); or attempted complete endovascular coil embolization 2-4 weeks later (n = 6; control group 2). Angiographic results were compared at baseline, immediately after RFA, and at 12 weeks, using an ordinal scale. Pathological results and neointima formation at the neck were compared using a semiquantitative grading scale. RESULTS Bipolar RFA was able to reliably target the aneurysm neck when the coil mass and stent were used as electrodes. RFA improved angiographic results immediately after partial coiling (p = 0.0024). Two RFA-related complications occurred, involving transient occlusion of 1 carotid artery and 1 hemorrhage from an adventitial arterial blister. At 12 weeks, angiographic results were improved with RFA (median score of 0), when compared with controls (median score of 2; p = 0.0013). Neointimal closure of the aneurysm neck was better with RFA compared with controls (p = 0.0003). CONCLUSIONS Bipolar RFA can improve results of embolization in experimental models by selectively ablating residual lesions after coil embolization. PMID- 27203148 TI - Introducing a new era of ischemic stroke care. PMID- 27203149 TI - BRAF V600E mutation and BRAF kinase inhibitors in conjunction with stereotactic radiosurgery for intracranial melanoma metastases. AB - OBJECTIVE Recent advancements in molecular biology have identified the BRAF mutation as a common mutation in melanoma. The wide use of BRAF kinase inhibitor ( BRAFi) in patients with metastatic melanoma has been established. The objective of this study was to examine the impact of BRAF mutation status and use of BRAFi in conjunction with stereotactic radiosurgery (SRS). METHODS This was a single center retrospective study. Patient's charts and electronic records were reviewed for date of diagnosis of primary malignancy, BRAF mutation status, chemotherapies used, date of the diagnosis of CNS metastases, date of SRS, survival, local tumor control after SRS, and adverse events. Patients were divided into 3 groups: Group A, those with mutant BRAF without BRAFi treatment (13 patients); Group B, those with mutant BRAF with BRAFi treatment (17 patients); and Group C, those with wild type BRAF (35 patients). Within a cohort of 65 patients with the known BRAF mutation status and treated with SRS between 2010 and 2014, 436 individual brain metastases (BMs) were identified. Kaplan-Meier methodology was then used to compare survival based on each binary parameter. RESULTS Median survival times after the diagnosis of melanoma BM and after SRS were favorable in patients with a BRAF mutation and treated with SRS in conjunction with BRAFi (Group B) compared with the patients with wild-type BRAF (Group C, 23 vs 8 months and 13 vs 5 months, respectively; p < 0.01, log-rank test). SRS provided a local tumor control rate of 89.4% in the entire cohort of patients. Furthermore, the local control rate was improved in the patients treated with SRS in conjunction with BRAFi (Group B) compared with patients with wild-type (Group C) or with BRAF mutation but no BRAFi (Group A) as an adjunct treatment for BMs. CONCLUSIONS BRAF mutation status appears to play an important role as a potent prognostic factor in patients harboring melanoma BM. BRAFi in conjunction with SRS may benefit this group of patients in terms of BM survival and SRS with an acceptable safety profile. PMID- 27203151 TI - Letter to the Editor: Augmented reality-guided neurosurgery. PMID- 27203150 TI - Comparison of clipping and coiling in elderly patients with unruptured cerebral aneurysms. AB - OBJECTIVE The comparative effectiveness of the 2 treatment options-surgical clipping and endovascular coiling-for unruptured cerebral aneurysms remains an issue of debate and has not been studied in clinical trials. The authors investigated the association between treatment method for unruptured cerebral aneurysms and outcomes in elderly patients. METHODS The authors performed a cohort study of 100% of Medicare fee-for-service claims data for elderly patients who had treatment for unruptured cerebral aneurysms between 2007 and 2012. To control for measured confounding, the authors used propensity score conditioning and inverse probability weighting with mixed effects to account for clustering at the level of the hospital referral region (HRR). An instrumental variable (regional rates of coiling) analysis was used to control for unmeasured confounding and to create pseudo-randomization on the treatment method. RESULTS During the study period, 8705 patients underwent treatment for unruptured cerebral aneurysms and met the study inclusion criteria. Of these patients, 2585 (29.7%) had surgical clipping and 6120 (70.3%) had endovascular coiling. Instrumental variable analysis demonstrated no difference between coiling and clipping in 1-year postoperative mortality (OR 1.25, 95% CI 0.68-2.31) or 90-day readmission rate (OR 1.04, 95% CI 0.66-1.62). However, clipping was associated with a greater likelihood of discharge to rehabilitation (OR 6.39, 95% CI 3.85 10.59) and 3.6 days longer length of stay (LOS; 95% CI 2.90-4.71). The same associations were present in propensity score-adjusted and inverse probability weighted models. CONCLUSIONS In a cohort of Medicare patients, there was no difference in mortality and the readmission rate between clipping and coiling of unruptured cerebral aneurysms. Clipping was associated with a higher rate of discharge to a rehabilitation facility and a longer LOS. PMID- 27203152 TI - The impact of stimulus arousal level on emotion regulation effectiveness in borderline personality disorder. AB - Basic emotion theory suggests that the effectiveness of different emotion regulation strategies vary with the intensity of the emotionally-salient stimulus. Although findings from studies using healthy samples are concordant with what is proposed by theory, it is unclear whether these relationships hold true among individuals with borderline personality disorder (BPD). Twenty-five individuals with BPD and 30 HCs were exposed to negative images of varying levels of emotional arousal and were instructed to either react as they normally would, distract, or use mindful awareness. Self-reported negativity ratings, heart rate, and skin conductance level (SCL) were monitored throughout. SCL data indicated that increases in image arousal resulted in larger reductions in SCL when distracting but not when implementing mindful awareness. Self-report data suggested that, in HCs, the effectiveness of mindful awareness decreased to a greater extent than distraction when image arousal increased. These findings are consistent with basic emotion research and suggest that some forms of emotion regulation (distraction) are more suited to high emotion arousal contexts than others (mindful awareness) and that, compared with HCs, individuals with BPD may be more resilient to the deteriorating effectiveness of mindful awareness with respect to increasing emotional arousal. PMID- 27203153 TI - Performance of Mini-Mental State Examination (MMSE) in long-stay patients with schizophrenia or schizoaffective disorders in a psychiatric institute. AB - Studies have found that age and education were associated with cognition in older adults. However, little is known how clinical factors (e.g. age of illness onset, length of hospital stay, type of antipsychotic medications, and duration of illness) are associated with cognitive functioning in patients with schizophrenia. This study aimed to examine the influence of socio-demographic and clinical factors on cognitive domains measured using Mini-Mental State Examination (MMSE) among patients with schizophrenia or schizoaffective disorders residing in a psychiatric institute in Singapore. A single-phase interview was conducted at the Institute of Mental Health (IMH) in patients diagnosed with schizophrenia or schizoaffective disorders (n=110). MMSE was administered to all participants. Data on socio-demographic characteristics, smoking, alcohol consumption, and medical history were collected. Age, gender, and level of education were significantly associated with MMSE scores. After adjusting for all socio-demographic correlates, longer length of hospital stay remained significant in predicting lower MMSE scores. Length of hospital stay was independently associated with cognitive functioning. Early interventions for cognition such as physical and mental exercises should be implemented for better prognosis. PMID- 27203154 TI - Electrical impedance tomography in 3D using two electrode planes: characterization and evaluation. AB - Electrical impedance tomography (EIT) uses body surface electrical stimulation and measurements to create conductivity images; it shows promise as a non invasive technology to monitor the distribution of lung ventilation. Most applications of EIT have placed electrodes in a 2D ring around the thorax, and thus produced 2D cross-sectional images. These images are unable to distinguish out-of-plane contributions, or to image volumetric effects. Volumetric EIT can be calculated using multiple electrode planes and a 3D reconstruction algorithm. However, while 3D reconstruction algorithms are available, little has been done to understand the performance of 3D EIT in terms of the measurement configurations available. The goal of this paper is to characterize the phantom and in vivo performance of 3D EIT with two electrode planes. First, phantom measurements are used to measure the reconstruction characteristics of seven stimulation and measurement configurations. Measurements were then performed on eight healthy volunteers as a function of body posture, postures, and with various electrode configurations. Phantom results indicate that 3D EIT using two rings of electrodes provides reasonable resolution in the electrode plane but low vertical resolution. For volunteers, functional EIT images are created from inhalation curve features to analyze the effect of posture (standing, sitting, supine and decline) on regional lung behaviour. An ability to detect vertical changes in lung volume distribution was shown for two electrode configurations. Based on tank and volunteer results, we recommend the use of the 'square' stimulation and measurement pattern for two electrode plane EIT. PMID- 27203155 TI - Intramyocardial injection of SERCA2a-expressing lentivirus improves myocardial function in doxorubicin-induced heart failure. AB - BACKGROUND: Doxorubicin is an effective anticancer drug. The major limitation to its use is the induction of dose-dependent cardiomyopathy. No specific treatment exists for doxorubicin-induced cardiomyopathy and treatments used for other forms of heart failure have only limited beneficial effects. The contraction-relaxation cycle of the heart is controlled by cytosolic calcium concentrations, which, in turn, are critically regulated by the activity of the sarcoplasmic reticulum Ca(2) (+) ATPase (SERCA2a) pump. We hypothesized that SERCA2a gene transfer would ameliorate doxorubicin-induced cardiomyopathy. METHODS: Lentiviral vectors LV SERCA2a-GFP and LV-GFP were constructed and in vitro gene transfer of LV-SERCA2a GFP confirmed SERCA2a expression by western blot analysis. Heart failure was induced by giving a single intraperitoneal injection of doxorubicin. LV-SERCA2a GFP, LV-GFP vectors and phosphate-buffered saline (PBS) were injected under echocardiographic control to the anterior wall of the left ventricle. RESULTS: Echocardiography analyses were performed on the injection day and 28 days postinjection. On the injection day, there were no significant differences in the average ejection fractions (EFs) among SERCA2a (40.0%), GFP (41.1%) and PBS (39.4%) injected animals. On day 28, EF in the SERCA2a group had increased by 16.6 +/- 6.7% to 46.4 +/- 2.1%. By contrast, EFs in the GFP (40.2 +/- 1.3%) and PBS (40.6 +/- 1.4%) groups remained at pre-injection levels. In addition, end systolic and end diastolic left ventricle volumes were significantly smaller in the SERCA2a group compared to controls. CONCLUSIONS: SERCA2a gene transfer significantly improves left ventricle function and dimensions in doxorubicin induced cardiomyopathy, thus making LV-SERCA2a gene transfer an attractive treatment modality for doxorubicin-induced heart failure. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27203156 TI - [Potentially toxic antibiotics concentrations after administration using impregnated dressing in a severe burned patient: A case report]. AB - Severe burned patients present high risk of skins infections, frequently due to Pseudomonas aeruginosa. Impregnated dressings with amikacin or colistin could be a good alternative to obtain effective concentration directly at the infected site. Therapeutic drug monitoring for these antibiotics is currently recommended after an intravenous administration to obtain effective and non-toxic plasmatic concentrations. However, data are lacking about systemic exposition and risk of toxicity after an administration with impregnated dressings. We report the case of a severe burned patient with cutaneous infection treated with amikacin and colistin impregnated dressings, for which plasmatic pharmacokinetic profiles were performed. PMID- 27203157 TI - Adverse health effects in children of women exposed in utero to diethylstilbestrol (DES). AB - OBJECTIVE: Exposure to diethylstilbestrol (DES) in utero is associated with adverse health effects, including genital anomalies in women and men, and cancers in women. Animal studies showed birth defects and tumors in the offspring of DES exposed mice, revealing transgenerational transmission of DES effects. In humans, birth defects, such as hypospadias were observed in children of prenatally exposed women. The aim of this research was to further assess the health effects in children of prenatally exposed women. METHODS: In a retrospective cohort study, the reports of women exposed to DES in utero on their 4409 children were compared with those of unexposed women on their 6203 children. Comparisons used odd ratios (OR) between children of exposed and unexposed women and standardized incidence rate (SIR) with the general population. These cohorts were recruited on a voluntary basis to answer questionnaires. RESULTS: There was a global increase of defects in children born to exposed women when compared with those born to unexposed (OR 2.29, 95% CI: 1.80-2.79, P<0.001) and with the general population (SIR 2.39, 95% CI: 2.11-2.68). Increased defects were observed in male genital tract, esophagus, lip or palate, musculoskeletal and circulatory systems. For female genital tract anomalies, there was no significant increase. However, this cohort being relatively young, further follow-up is needed. An increase of cerebral palsy was revealed. The incidence of cancers was not increased, in particular for breast, uterus and ovary. CONCLUSION: Our results confirmed a transgenerational transmission of defects in male genital tract. With caution due to possible bias associated with this method, our data suggest an increase of defects for esophagus, lip or palate, musculoskeletal and circulatory system in children of exposed women. PMID- 27203158 TI - [Early adherence to anti-glaucoma therapy: An observational study]. AB - OBJECTIVES: Glaucoma is a major cause of blindness, preventable by a regular therapy. Thus, a good knowledge of patients' adherence to preventive therapy is critical to improve disease management. Early persistence to first-line glaucoma therapy is poorly documented in France. We verified to what extent first-line glaucoma therapy was interrupted within the 12 months following initiation and how this interruption varied with patients' characteristics and drug classes. METHODS: Patients newly-treated with chronic glaucoma therapy (prostaglandins, beta-blockers alone or combined with another therapy, and topical carbonic anhydrase inhibitors) between 2005 and 2008 were identified in the French National Claims data (1/97th random sample). Twelve-month persistence was defined by the presence of the first-line drug class (>=1dispensation) between the 12th and 24th months following initiation. Twelve-month persistence was compared between patients according to the first-line drug classes and baseline characteristics. Proportion of days covered (12 months) and number of quarters with initiated drug class (24 months) were also studied. RESULTS: Among 5331 patients initiated with chronic glaucoma therapy in monotherapy (63% aged >=60 years old, 57% females), initiated therapy mainly consisted of prostaglandins (43%) and beta-blockers alone (32%). Only 45% of the patients were persistent to first-line therapy 12 months after initiation. Salient differences in persistence rates appeared between drug classes (P<0.0001): from 59% with prostaglandins to 26% for topical carbonic anhydrase inhibitors. Better results also appeared for prostaglandins with other dimensions of adherence. Non-persistent patients were more likely younger than 40, or conversely aged>=80 (P<0.0001). They were also more likely to necessitate social assistance for therapy (P=0.0007). No salient difference appeared as to gender. CONCLUSIONS: Our findings confirm the low early persistence of first-line therapy, despite better results for prostaglandins. Education of patients and identification of barriers to adherence could contribute to improve quality of care. PMID- 27203159 TI - Quinine unbound concentration is the best marker for therapeutic drug monitoring. AB - Quinine monitoring should be based on unbound concentration due to variable unbound fraction in malaria patients. PMID- 27203160 TI - Consequences of erroneous phone transmission of tacrolimus blood concentration: A case report. PMID- 27203161 TI - [Cerebral venous thrombosis in a Parkinson's disease patient: An unusual case report with low-dose clozapine]. PMID- 27203162 TI - [Investigation of the medical and social situation of patients managed by opiate replacement regimens for over 10 years by their GP]. AB - OBJECTIVE: Management with opiate replacement regimens (ORRs) of patients presenting to primary care settings with opiate addiction has become a long-term follow-up. The aim of this survey study was to describe patients who had been prescribed ORRs for at least 10 years by their general practitioner (GP). METHOD: In 2011, two questionnaires were sent to a sample of 38 GPs prescribing ORRs in Northern France. Doctors' questionnaires collected their typology and opinions on their patients receiving opiate substitution treatments for over 10 years. Patients' questionnaires were completed in the presence of the patient. RESULTS: Twenty-three doctors' and 83 patients' questionnaires were suitable for analysis. The average number of listed ORR patients was 14.2 and 3.6 had been managed for 10 years or more. Misuse persisted: 30.5% of GPs considered that it was carried out by at least by 15% of patients. Average dosages were 60.3 mg for methadone and 7.0 mg for buprenorphine. Employment (46.3% of patients had a salary), dwelling and family live (46.3% of patients were in charge of children) were favored. Nevertheless, precariousness persisted: 32% of patients were indebted and help of social workers was not systematically searched. One third of the patients were alcohol and cannabis misusers, 70% were smoking and 34.5% multiple drug misusers. An important number of patients were taking anxiolytics (37.8%) and hypnotics (30.5%). CONCLUSION: After 10 years of follow-up for an ORR by a GP, the social situation of patients seems to have stabilized, but psychoactive drugs consumption remains important. PMID- 27203163 TI - Minimal-change disease and interstitial nephritis secondary to non-steroidal anti inflammatory drugs (naproxen). PMID- 27203164 TI - Evaluation of best corrected visual acuity and central macular thickness after intravitreal dexamethasone implant injections in patients with Irvine-Gass syndrome: A retrospective study of six cases. AB - PURPOSE: Irvine-Gass syndrome is a macular edema (ME) that specifically occurs after cataract surgery. Its incidence varies from 0.2-2%. The purpose of this study is to evaluate the effectiveness of intravitreal dexamethasone implant injections in patients with Irvine-Gass syndrome. METHODS: Patients with ME secondary to cataract surgery who underwent intravitreal injections of dexamethasone implant between December 2011 to October 2014 at Francois-Quesnay hospital (Mantes-la-Jolie, France) were retrospectively reviewed. The patients were followed for at least 10 months. All the patients were handled by intravitreal injection of dexamethasone in the eye of study among which some resisted to a preliminary treatment by non-steroidal anti-inflammatory drug (NSAID) and acetazolamide. The patients were examined each month. The patients were again handled by intravitreal injection of dexamethasone if they presented a recurrence. The primary endpoint of the study was determined on best corrected visual acuity (BCVA) using early diabetic retinopathy study (ETDRS) scale and central macular thickness (CMT) [MUm] using optical coherence tomography (OCT) 3 and 6 months after the first injection. Secondary endpoints were the number of recurrences, the number of injections, the duration average before the first recurrence, the BCVA 10 months after the first injection and the tolerance. RESULTS: Six eyes of six patients were studied. At baseline, the mean (standard deviation [SD]) of the BCVA was 59.8+/-11. Three months after the first injection, the mean (SD) of the BCVA showed a statistically significant increase to 72.2+/-8.6 (P=0.03). Six months after the first injection, the mean (SD) of the BCVA showed a statistically significant increase to 72+/-11.8 (P=0.03). Concerning the CMT, the mean (SD) was 495.6+/-135.2 before treatment. Three months after the first injection, the mean (SD) of the CMT showed a statistically significant decrease to 268.6+/-57.8 (P=0.03). Six months after the first injection, the mean (SD) of the CMT showed a significant decrease to 350.1+/-56.3 (P=0.09). CONCLUSION: In this study, both mean BCVA and mean CMT had significantly improved from baseline after treatment with dexamethasone implant in patients with Irvine-Gass syndrome. PMID- 27203165 TI - [Adverse drug reactions in pediatrics: Experience of a regional pharmacovigilance center]. AB - AIM: To describe the adverse drug reactions (ADR) and the drugs involved in pediatrics. METHODS: An observational study on all ADR notifications recorded in the French pharmacovigilance database by the Regional Pharmacovigilance Center of Champagne-Ardenne between 1 January 1985 and 31 December 2014 involving children from 0 to 17 years inclusive was performed. For all notifications, we studied the patient and the ADR characteristics. RESULTS: During the study period, 632 notifications were collected. The most frequently reported ATC (anatomical, therapeutic and chemical) classes were vaccines (15.9%), antineoplastics (12%) and antibiotics (11.1%). Forty-six percent of the notifications were serious. For serious ADRs, the most involved drugs were paracetamol, asparaginase and ibuprofen. Skin reactions were the most often reported ADRs. The most common lowest level terms (LLT) were urticaria (4.9%), hypersensitivity (4.1%), fever (2.9%) and vomiting (2.8%). CONCLUSION: ADR reporting to the pharmacovigilance system, in particular pediatric ADRs, should be encouraged. Information on the use of medicinal products, especially on self-medication use, need to be improve. PMID- 27203166 TI - [Pregnancy outcome after preconceptional exposure to methotrexate for ectopic pregnancy]. AB - INTRODUCTION: Methotrexate (MTX) is a known teratogenic drug used off-label in the treatment of ectopic pregnancies (EP). As MTX polyglutamated derivatives remains into the cells during several weeks, it is recommended to avoid conception during 3 to 6 months following MTX therapy. We report the follow-up of pregnancies after preconceptional exposure to MTX for EP. MATERIAL/METHODS: Prospective cases of pregnancy occurring within 3 months after MTX injection for an EP recorded in the Terappel database were analyzed. RESULTS: Data were obtained on 52 pregnant women. The median age of patients was 28 (18-38), and the median gestational age at inclusion was 7 weeks after last menstrual period (3 22). The time between the last MTX injection and conception ranged from 12 days to 13 weeks and the total MTX dose was between 40 to 210mg. Out of 45 pregnancies with known outcome, there were 39 live births (87%), 3 spontaneous abortions (6.7%) occurring 63 to 94 days after MTX administration, 2 elective terminations, and 1 medical termination after premature rupture of membranes, oligohydramnios and arthrogryposis (48mg of MTX 9 and 8 weeks before conception). Two additional cases of major malformations were observed among 40 examinable babies or fetuses: tetralogy of Fallot (MTX 6 weeks before conception), and cerebral ventriculomegaly with normal karyotype (50mg of MTX 9 to 13 weeks before conception). The resulting rate of major malformations was 7.5% (95% CI: 1.6 20.4). DISCUSSION/CONCLUSION: Although this prospective study shows a major malformation rate higher than expected in the general population, the observed malformations are not consistent with the typical pattern of methotrexate embryopathy. However, the case of tetralogy of Fallot is reminiscent of previously published cases with MTX exposure during early pregnancy. Owing to the small sample size, more powerful studies are needed to confirm or refute these findings. PMID- 27203167 TI - [Drugs and retinal disorders: A case/non-case study in the French pharmacovigilance database]. AB - Retina is the part of the eye suffering most damage from pharmaceutical molecules. Drug-induced retinopathies have been described but data are scarce and sometimes conflicting especially concerning its potential seriousness. The aim of this study was to investigate potential associations between drugs and retinal disorders using the French Pharmacovigilance data. We used the case/non-case method in the French PharmacoVigilance Database (FPVD) to identify drugs able to induce retinopathies. Cases were reports of retinal disorders in the FPVD between January 2008 and December 2012. Non-cases were all other reports during the same period. To assess the association between retinopathy and drug intake, we calculated the odds-ratio (OR) [with their 95% confidence intervals] for all drugs associated with at least 3 cases of retinopathy. Among the 123 687 adverse drug reactions recorded during the studied period, we identified 164 cases of retinal disorders. Significant associations were found for 11 drugs. The main therapeutic classes were antirhumatismals (hydroxychloroquine, chloroquine and etanercept: 18 cases), anti-infective (ribavirine, PEG-interferon-alfa-2a and cefuroxime: 16 cases) and antineoplastic drugs (imatinib and letrozole: 8 cases. Three other drugs were also found: raloxifene (5 cases), erythropoietin beta (4 cases) and ranibizumab (3 cases). Taking into account the limits of the methodology, our study confirmed the association between retinopathy and some expected drugs such as aminoquinolines, interferons, imatinib or ranibizumab. Other drugs like erythropoietin beta, cefuroxime, letrozole and etanercept were significantly associated with retinal disorders although this was not or poorly described in the literature. Thus, further prospective studies are necessary to confirm such associations. PMID- 27203168 TI - Pharmacists' different profiles characterization about opioid substitution treatments. AB - INTRODUCTION: Delivering practices of opioid substitution treatment (OST) in community pharmacies are heterogeneous. This study aims at drawing up an inventory and at characterizing different populations of pharmacists, regarding their practices and perceptions. METHODS: We distributed a questionnaire to pharmacists, which was divided into two parts: socio-demographic questions, and 49 binary questions collecting pharmacists' perceptions. Statistical analyses were performed using SAS 9.3 and SPAD7 software. The categorical variables were expressed as numbers and percentages. We characterized the different profiles of pharmacists using a multivariate analysis method. RESULTS: We analyzed 303 questionnaires; 60.8% of our cross-section of pharmacists consider that OSTs are a treatment for chronic disease, a treatment in which they consider that they play a key role. Regarding OSTs, 89.3% felt "comfortable" with current regulations, while 77.3% have mastered possible interactions with other drugs. 16.8% of pharmacists equate the act of delivering OSTs as a "legal narcotic deal". Regarding the patients, 49.2% of pharmacists consider them as "different", and 39.1% fear that they cause relationship problems. Most pharmacists perceive the role they are meant to play, although a lack of training and the need for recommendations have been highlighted. PCA allowed us to characterize 4 different profiles of pharmacists. CONCLUSION: Continuous training adapted to the different profiles we drew up will be offered in order to allow pharmacists to deepen their knowledge about drug dependence and related care support. PMID- 27203169 TI - Fatal tramadol-induced multiple organ failure. PMID- 27203170 TI - [Vascular calcifications, the hidden side effects of vitamin K antagonists]. AB - Despite the availability of new oral anticoagulants, vitamin K antagonists (VKA, such as fluindione, acenocoumarol or warfarin) remain currently the goal standard medicines for oral prevention or treatment of thromboembolic disorders. They inhibit the cycle of the vitamin K and its participation in the enzymatic gamma carboxylation of many proteins. The VKA prevent the activation of the vitamin K dependent blood clotting factors limiting thus the initiation of the coagulation cascade. But other proteins are vitamin K-dependent and also remain inactive in the presence of VKA. This is the case of matrix Gla-protein (MGP), a protein that plays a major inhibitory role in the development of vascular calcifications. Several experimental and epidemiological results suggest that the use of the VKA could promote the development of vascular calcifications increasing thus the cardiovascular risk. This risk seems to be higher in patients with chronic kidney disease or mellitus diabetes who are more likely to develop vascular calcifications, and may be due to a decrease of the MGP activity. This review aims at summarizing the data currently available making vascular calcifications the probably underestimated side effects of VKA. PMID- 27203171 TI - [Practical information for therapeutic drug monitoring of the most common compounds]. AB - This article reports the main information for the interpretation of blood concentrations of most common drugs measured in pharmacology-toxicology departments: acetaminophen, amikacin, carbamazepine, digoxin, gentamicin, lithium, methotrexate, phenobarbital, phenytoin and valproic acid. PMID- 27203172 TI - [Use of psychostimulants in a sexual context: Analysis of cases reported to the French network of Addictovigilance Centers]. AB - The "SLAM" phenomenon is an increasingly popular practice, in Paris and London gay scene, defined by 3 characteristics: injection, sexual party and psychostimulant drugs. The French Medical Agency requested a risk assessment of "SLAM" and more broadly of the use of psychostimulants in a sexual context, by the analysis of complications related to this practice notified to the French Network of Addictovigilance Centers. All cases of complications related to "SLAM" practice, including cases of abuse or dependence, and somatic and psychiatric complications, were analysed. Between January 2008 to December 2013, 51 cases were collected. Users were exclusively men, with a mean age of 40 years, having psychostimulants exposure in a sexual context, mainly in men who have sex with men (MSM) context (100%, n=35). The prevalence of human immunodeficiency virus (HIV) infection was 82% (n=32) with a high level of HIV/hepatitis C virus (HCV) co-infection (50%, n=16). The main psychostimulants reported are synthetic cathinones (89.5%). Cathinones users tended to be polydrug users: 62% also reported use other than psychoactive substances (gamma-butyrolactone [GBL], ketamine, methylenedioxymethamphetamine [MDMA], lysergic acid diethylamide [LSD]...). The main complications were psychiatric disorders in 50% (psychotic symptoms, agitation, anxiety, suicidal ideas or attempt and forensic problems), acute intoxication in 25% (including 3 deaths), dependence and abuse in 17% and infectious complications in 8% (viral seroconversion). Health professionals as well as users should be aware of the physical (cardiovascular) and behavioural (psychic, fast dependence syndrome) toxicity of cathinones. Risk reduction policy must be targeted to the population of MSM with specific interventions both on risky sexual behavior and substance use. PMID- 27203173 TI - Defective Autophagy Initiates Malignant Transformation. AB - In this issue of Molecular Cell, Park et al. (2016) elegantly demonstrate that a partial defect in autophagy supports malignant transformation as it favors the production of genotoxic reactive oxygen species by mitochondria. PMID- 27203174 TI - The Incredible ULKs: Autophagy and Beyond. AB - Atg1 integrates nutrient status and autophagy. In this issue, Joo et al. (2016) reveal that the mammalian Atg1 homologs ULK1/2 are dispensable for neuronal basal autophagy. ULK1/2 phosphorylate SEC16A and regulate ER export, expanding the autophagy-independent functions of autophagy proteins. PMID- 27203175 TI - CRISPR-Mediated Base Editing without DNA Double-Strand Breaks. AB - Targeting point mutations using CRISPR/Cas9 so far has required efficient homologous recombination (HR) and donor oligonucleotides. In a recent Nature paper, Komor and colleagues (2016) describe a way to make specific base changes that does not depend on HR or donor DNA and does not involve making double-strand breaks. PMID- 27203176 TI - The Noncanonical Role of ULK/ATG1 in ER-to-Golgi Trafficking Is Essential for Cellular Homeostasis. AB - ULK1 and ULK2 are thought to be essential for initiating autophagy, and Ulk1/2 deficient mice die perinatally of autophagy-related defects. Therefore, we used a conditional knockout approach to investigate the roles of ULK1/2 in the brain. Although the mice showed neuronal degeneration, the neurons showed no accumulation of P62(+)/ubiquitin(+) inclusions or abnormal membranous structures, which are observed in mice lacking other autophagy genes. Rather, neuronal death was associated with activation of the unfolded protein response (UPR) pathway. An unbiased proteomics approach identified SEC16A as an ULK1/2 interaction partner. ULK-mediated phosphorylation of SEC16A regulated the assembly of endoplasmic reticulum (ER) exit sites and ER-to-Golgi trafficking of specific cargo, and did not require other autophagy proteins (e.g., ATG13). The defect in ER-to-Golgi trafficking activated the UPR pathway in ULK-deficient cells; both processes were reversed upon expression of SEC16A with a phosphomimetic substitution. Thus, the regulation of ER-to-Golgi trafficking by ULK1/2 is essential for cellular homeostasis. PMID- 27203177 TI - Autophagic UVRAG Promotes UV-Induced Photolesion Repair by Activation of the CRL4(DDB2) E3 Ligase. AB - UV-induced DNA damage, a major risk factor for skin cancers, is primarily repaired by nucleotide excision repair (NER). UV radiation resistance-associated gene (UVRAG) is a tumor suppressor involved in autophagy. It was initially isolated as a cDNA partially complementing UV sensitivity in xeroderma pigmentosum (XP), but this was not explored further. Here we show that UVRAG plays an integral role in UV-induced DNA damage repair. It localizes to photolesions and associates with DDB1 to promote the assembly and activity of the DDB2-DDB1-Cul4A-Roc1 (CRL4(DDB2)) ubiquitin ligase complex, leading to efficient XPC recruitment and global genomic NER. UVRAG depletion decreased substrate handover to XPC and conferred UV-damage hypersensitivity. We confirmed the importance of UVRAG for UV-damage tolerance using a Drosophila model. Furthermore, increased UV-signature mutations in melanoma correlate with reduced expression of UVRAG. Our results identify UVRAG as a regulator of CRL4(DDB2) mediated NER and suggest that its expression levels may influence melanoma predisposition. PMID- 27203179 TI - Cyclin-Dependent Kinase Co-Ordinates Carbohydrate Metabolism and Cell Cycle in S. cerevisiae. AB - Cyclin-dependent kinases (CDKs) control cell division in eukaryotes by phosphorylating proteins involved in division. But successful proliferation requires co-ordination between division and cellular growth in mass. Previous proteomic studies suggested that metabolic proteins, as well as cell division proteins, could potentially be substrates of cyclin-dependent kinases. Here we focus on two metabolic enzymes of the yeast S. cerevisiae, neutral trehalase (Nth1) and glycogen phosphorylase (Gph1), and show that their activities are likely directly controlled by CDK activity, thus allowing co-ordinate regulation of carbohydrate metabolism with cell division processes. In this case, co ordinate regulation may optimize the decision to undertake a final cell division as nutrients are being exhausted. Co-regulation of cell division processes and metabolic processes by CDK activity may be a general phenomenon important for co ordinating the cell cycle with growth. PMID- 27203178 TI - The Yeast Cyclin-Dependent Kinase Routes Carbon Fluxes to Fuel Cell Cycle Progression. AB - Cell division entails a sequence of processes whose specific demands for biosynthetic precursors and energy place dynamic requirements on metabolism. However, little is known about how metabolic fluxes are coordinated with the cell division cycle. Here, we examine budding yeast to show that more than half of all measured metabolites change significantly through the cell division cycle. Cell cycle-dependent changes in central carbon metabolism are controlled by the cyclin dependent kinase (Cdk1), a major cell cycle regulator, and the metabolic regulator protein kinase A. At the G1/S transition, Cdk1 phosphorylates and activates the enzyme Nth1, which funnels the storage carbohydrate trehalose into central carbon metabolism. Trehalose utilization fuels anabolic processes required to reliably complete cell division. Thus, the cell cycle entrains carbon metabolism to fuel biosynthesis. Because the oscillation of Cdk activity is a conserved feature of the eukaryotic cell cycle, we anticipate its frequent use in dynamically regulating metabolism for efficient proliferation. PMID- 27203180 TI - Recognition of Lys48-Linked Di-ubiquitin and Deubiquitinating Activities of the SARS Coronavirus Papain-like Protease. AB - Deubiquitinating enzymes (DUBs) recognize and cleave linkage-specific polyubiquitin (polyUb) chains, but mechanisms underlying specificity remain elusive in many cases. The severe acute respiratory syndrome (SARS) coronavirus papain-like protease (PLpro) is a DUB that cleaves ISG15, a two-domain Ub-like protein, and Lys48-linked polyUb chains, releasing diUb(Lys48) products. To elucidate this specificity, we report the 2.85 A crystal structure of SARS PLpro bound to a diUb(Lys48) activity-based probe. SARS PLpro binds diUb(Lys48) in an extended conformation via two contact sites, S1 and S2, which are proximal and distal to the active site, respectively. We show that specificity for polyUb(Lys48) chains is predicated on contacts in the S2 site and enhanced by an S1-S1' preference for a Lys48 linkage across the active site. In contrast, ISG15 specificity is dominated by contacts in the S1 site. Determinants revealed for polyUb(Lys48) specificity should prove useful in understanding PLpro deubiquitinating activities in coronavirus infections. PMID- 27203181 TI - Structural Analysis of dsRNA Binding to Anti-viral Pattern Recognition Receptors LGP2 and MDA5. AB - RIG-I and MDA5 sense virus-derived short 5'ppp blunt-ended or long dsRNA, respectively, causing interferon production. Non-signaling LGP2 appears to positively and negatively regulate MDA5 and RIG-I signaling, respectively. Co crystal structures of chicken (ch) LGP2 with dsRNA display a fully or semi-closed conformation depending on the presence or absence of nucleotide. LGP2 caps blunt, 3' or 5' overhang dsRNA ends with 1 bp longer overall footprint than RIG-I. Structures of 1:1 and 2:1 complexes of chMDA5 with short dsRNA reveal head-to head packing rather than the polar head-to-tail orientation described for long filaments. chLGP2 and chMDA5 make filaments with a similar axial repeat, although less co-operatively for chLGP2. Overall, LGP2 resembles a chimera combining a MDA5-like helicase domain and RIG-I like CTD supporting both stem and end binding. Functionally, RNA binding is required for LGP2-mediated enhancement of MDA5 activation. We propose that LGP2 end-binding may promote nucleation of MDA5 oligomerization on dsRNA. PMID- 27203182 TI - CRL4(WDR23)-Mediated SLBP Ubiquitylation Ensures Histone Supply during DNA Replication. AB - To maintain genome integrity and epigenetic information, mammalian cells must carefully coordinate the supply and deposition of histones during DNA replication. Here we report that the CUL4 E3 ubiquitin ligase complex CRL4(WDR23) directly regulates the stem-loop binding protein (SLBP), which orchestrates the life cycle of histone transcripts including their stability, maturation, and translation. Lack of CRL4(WDR23) activity is characterized by depletion of histones resulting in inhibited DNA replication and a severe slowdown of growth in human cells. Detailed analysis revealed that CRL4(WDR23) is required for efficient histone mRNA 3' end processing to produce mature histone mRNAs for translation. CRL4(WDR23) binds and ubiquitylates SLBP in vitro and in vivo, and this modification activates SLBP function in histone mRNA 3' end processing without affecting its protein levels. Together, these results establish a mechanism by which CUL4 regulates DNA replication and possible additional chromatin transactions by controlling the concerted expression of core histones. PMID- 27203183 TI - Residential cognitive-behavioral weight-loss intervention for obesity with and without binge-eating disorder: A prospective case-control study with five-year follow-up. AB - OBJECTIVE: The aim of this prospective case-control study was to compare the long term effects of a residential cognitive-behavioral treatment (CBT) for weight loss in severely obese patients with and without binge-eating disorder (BED). METHODS: We assessed weight-loss outcomes and psychological impairment in 54 severely obese female patients with BED and 54 patients matched by age, gender, and body mass index (BMI) without BED admitted to a residential CBT program. Body weight was measured at baseline and at 6-month follow-up and was reported by patients in a telephone interview at 5-year follow-up. Depression, eating disorder psychopathology, general psychopathology, and quality of life were assessed using validated instruments at baseline and at 6-month follow-up. RESULTS: Obese patients with and without BED had similar weight loss at 6-month and 5-year follow-ups. Although both groups showed improved psychosocial variables, at 6 months the BED group maintained higher psychological impairment. Nevertheless, at 5-year follow-up more than half of the BED participants were no longer classifiable as having BED. DISCUSSION: The presence of BED does not affect weight-loss outcome in obese patients treated with the residential CBT for weight loss program considered. (c) 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2016; 49:723-730). PMID- 27203184 TI - 3D EIT image reconstruction with GREIT. AB - Most applications of thoracic EIT use a single plane of electrodes on the chest from which a transverse image 'slice' is calculated. However, interpretation of EIT images is made difficult by the large region above and below the electrode plane to which EIT is sensitive. Volumetric EIT images using two (or more) electrode planes should help compensate, but are little used currently. The Graz consensus reconstruction algorithm for EIT (GREIT) has become popular in lung EIT. One shortcoming of the original formulation of GREIT is its restriction to reconstruction onto a 2D planar image. We present an extension of the GREIT algorithm to 3D and develop open-source tools to evaluate its performance as a function of the choice of stimulation and measurement pattern. Results show 3D GREIT using two electrode layers has significantly more uniform sensitivity profiles through the chest region. Overall, the advantages of 3D EIT are compelling. PMID- 27203185 TI - Use of decision aids for shared decision making in venous thromboembolism: A systematic review. AB - BACKGROUND: Optimal care of patients with venous thromboembolism requires the input of patient preferences into clinical decision-making. However, the availability and impact of decision aids to facilitate shared decision making in care of venous thromboembolism is not well known. OBJECTIVES: To assess the availability, clinical impact and outcomes associated with the use of decision aids in patients with or at risk for venous thromboembolism. PATIENTS/METHODS: A systematic review of the literature was performed exploring the use of decision aids in patients with venous thromboembolism. Criteria for primary inclusion required use of patient values clarification in the decision aid. A secondary review without the requirement of a patient values clarification was performed to be more inclusive. The data was summarized such that knowledge gaps and opportunities for enquiry were identified. RESULTS: The primary review identified one study that explored the decision to extend anticoagulation in patients with a recent venous thromboembolism beyond the stipulated 3-month duration. The secondary review identified an additional study exploring the decision to undergo computer tomography testing in patients at low risk for pulmonary embolism in an emergency department setting. Both studies were of modest quality given a lack of control group for comparison analysis. CONCLUSIONS: Despite numerous calls to increase use of shared decision-making, a paucity of data exists to help patients engage in the treatment decisions for venous thromboembolism. Future studies of additional VTE clinical decisions with longer-term clinical outcomes appear necessary. PMID- 27203186 TI - Generation and application of bessel beams in electron microscopy. AB - We report a systematic treatment of the holographic generation of electron Bessel beams, with a view to applications in electron microscopy. We describe in detail the theory underlying hologram patterning, as well as the actual electron-optical configuration used experimentally. We show that by optimizing our nanofabrication recipe, electron Bessel beams can be generated with relative efficiencies reaching 37+/-3%. We also demonstrate by tuning various hologram parameters that electron Bessel beams can be produced with many visible rings, making them ideal for interferometric applications, or in more highly localized forms with fewer rings, more suitable for imaging. We describe the settings required to tune beam localization in this way, and explore beam and hologram configurations that allow the convergences and topological charges of electron Bessel beams to be controlled. We also characterize the phase structure of the Bessel beams generated with our technique, using a simulation procedure that accounts for imperfections in the hologram manufacturing process. PMID- 27203187 TI - Strategies for new and improved vaccines against ticks and tick-borne diseases. AB - Ticks infest a variety of animal species and transmit pathogens causing disease in both humans and animals worldwide. Tick-host-pathogen interactions have evolved through dynamic processes that accommodated the genetic traits of the hosts, pathogens transmitted and the vector tick species that mediate their development and survival. New approaches for tick control are dependent on defining molecular interactions between hosts, ticks and pathogens to allow for discovery of key molecules that could be tested in vaccines or new generation therapeutics for intervention of tick-pathogen cycles. Currently, tick vaccines constitute an effective and environmentally sound approach for the control of ticks and the transmission of the associated tick-borne diseases. New candidate protective antigens will most likely be identified by focusing on proteins with relevant biological function in the feeding, reproduction, development, immune response, subversion of host immunity of the tick vector and/or molecules vital for pathogen infection and transmission. This review addresses different approaches and strategies used for the discovery of protective antigens, including focusing on relevant tick biological functions and proteins, reverse genetics, vaccinomics and tick protein evolution and interactomics. New and improved tick vaccines will most likely contain multiple antigens to control tick infestations and pathogen infection and transmission. PMID- 27203188 TI - Value of the QRS-T area angle in improving the prediction of sudden cardiac death after acute coronary syndromes. AB - BACKGROUND: Prediction of sudden cardiac death (SCD) after acute coronary syndromes (ACS) remains a challenge. Although electrophysiology measures obtained by 3-D vectorcardiography (VCG) shortly after ACS may be useful predictors of SCD, they have not been adopted into clinical practice. The main objective of our study was to assess whether the VCG-derived QRS-T area angle (between area vectors) and the QRS-T angle (between maximum vectors) have additional value beyond standard risk factors in predicting SCD after ACS. METHODS AND RESULTS: We studied 643 consecutive ACS patients for whom data on VCG and echocardiography during the index hospitalization were available. Seventy-seven patients (12%) died, 37 (6%) from SCD and 21 (3%) from other cardiac causes during the 30-month follow-up. After adjusting for 9 standard risk factors (age, sex, diabetes, previous stroke, left ventricular ejection fraction; and estimated glomerular filtration rate, heart rate, systolic blood pressure<100mmHg, and Killip class>1 on admission), QRS-T area angle and QRS-T angle were shown to have independent predictive value for both SCD and all cardiac deaths. Reclassification analysis showed that both measures had additional predictive value beyond the 9 standard risk factors. For SCD, net reclassification improvements for QRS-T area angle and QRS-T angle were 46% and 45% and relative integrated discriminative improvements were 16% and 13% (vs the average~11% of the 9 standard risk factors). CONCLUSIONS: The VCG-derived QRS-T area angle and QRS-T angle improved prediction of SCD after ACS beyond standard risk factors. Further evaluation of their clinical utility and cost-effectiveness is therefore warranted. PMID- 27203189 TI - Characteristics of anticancer drug studies registered on the Chinese Clinical Trial Registry (ChiCTR) from 2007 to 2015. AB - OBJECTIVE: This research aims to examine the basic and methodological characteristics of anticancer drug studies registered on the Chinese Clinical Trial Registry (ChiCTR) and explores the progress of implementation of good clinical practice (GCP) and the challenges it poses for anticancer drug research in China. METHODS: The studies from 2007 to 2015 were downloaded from the ChiCTR and those involving anticancer drugs with evaluation of the main dimensions. The numerical trend of the studies registered each year was analyzed. Chi-square tests were performed to test for significant differences between different funding sources, types of drug and study phases. RESULTS: Six hundred and four anticancer drug studies were collected. The overall number of anticancer drug studies was increased. Significant differences could be seen in the dimensions of multicentre study (P = 0.000), participant number (P = 0.029) and randomization procedure (P = 0.005) for the three funding sources. There were significant differences in the dimensions of multicentre study (P = 0.001), participant number (P = 0.025), collecting samples from participants (P = 0.006), and randomization procedure (P = 0.009) between different kinds of drugs. There were also significant differences in the dimension of participant number (P = 0.025) and randomization procedure (P = 0.016) between different study phases. CONCLUSION: There are problems with study registry criteria and study type classification method. Also, within the studies researched, heterogeneity exists for various dimensions. Different sources of funding, distinct types of drug and disparate phases of study lead to significant differences in certain dimensions of anticancer drug studies. PMID- 27203190 TI - Seven Reasons To Be Concerned About the Use of the New Preimplantation Genetic Screening (PGS). PMID- 27203191 TI - Impact of the Number and Quality of Embryos Transferred in Multiple and Single Pregnancies. AB - OBJECTIVE: To investigate the relation between maternal age and embryo quality in choosing how many embryos should be transferred to obtain high pregnancy rates with minimal risk of multiple gestations. METHODS: Cross-sectional study, with secondary data analysis, including infertile couples undergoing Intracytoplasmic Sperm Injection, between 2005-2013, in the Assisted Fertilization Center - Fertility. The data was analyzed using the SPSS 16.0, in a descriptive and bivariate way using the chi-square test, P <0.05. Approved by the CEP UNISUL. RESULTS: 54.8% of pregnancies occurred with women <= 35 years. The prevalence of single pregnancy was 2.42 times the multiple pregnancies and no significant increase in multiplicity in the transfer of 3 or 4 embryos. The percentage of positive pregnancies was prevalent in the age group <= 35 years, regardless of embryo quality. Regardless of age, the greater the number of high quality transferred embryos, the higher the multiplicity. This was not observed with low quality embryos. With high quality embryos, the prevalence of positive pregnancies in middle age women was 9% lower when compared to those aged <= 35 years, with a P = 0,310. With low-quality embryos, the prevalence of positive pregnancy in this age group was 39% lower when compared to those aged <= 35 years, with a P < 0.01. CONCLUSION: The greater the number of high quality transferred embryos, the higher the multiplicity. However, this relationship is not true for low quality embryos. When only high quality embryos are transferred, the patients with intermediate age have similar pregnancy results to those from younger patients. Already with low-quality embryos, this same age group presents similar pregnancy results to older patients. PMID- 27203192 TI - Assisted Conception Services and Regulation within the Brazilian Context. AB - OBJECTIVE: The aim of this article was to analyze the social, ethical, and legal aspects related to assisted conception in Brazil. METHODS: This paper was based on preliminary data extracted from research "Assisted Reproduction in Brazil: Demographic, Social Aspects and Implications for Public Policy". This study aimed to investigate the private and public supply, the availability, and the criteria to allow access to reproductive technologies within the realms of public services, government regulations and legislation, professional association guidelines, and self-regulations, in addition to the ensuing ethical and social implications. The data comprises interviews with fertility specialists; Federal Board of Medicine resolutions on assisted conception; technical standards set by the Brazilian Health Surveillance Agency; participant observation; and detailed field notes of the Congresses of the Brazilian Society for Assisted Conception. RESULTS: Health care services have been unable to meet the growing demand for infertility treatment. Assisted reproductive technologies are mainly offered by private clinics at a very high cost. There is no specific legislation regulating assisted conception in Brazil. Bills aimed to regulate it are markedly influenced by religious views and moral judgment. Evangelical and Catholic members of Congress against procedures involving the manipulation of embryos hamper discussions on the topic. CONCLUSION: In the absence of state regulation, resolutions of the Federal Board of Medicine are filling the gap. Regarding all reproductive rights, equitable access to assisted conception care is dependent on public health services. PMID- 27203193 TI - Embryo Transfer Catheters: Softer is Easier. AB - OBJECTIVE: This study aimed to compare the use of semi-rigid and flexible catheters in terms of pregnancy rate and level of difficulty of the embryo transfer (ET) procedure. METHODS: Seven hundred and thirty-nine consecutive follicular aspirations for IVF or ICSI performed in our private fertility clinic within a 30-month period were randomly divided into two groups. Patients were allocated to either of the groups at the time of follicular retrieval with the aid of a random number generator according to the catheter used in ET: Group 1 (n = 370) - Frydman Classic Catheter 4.5 catheters; and Group 2 (n = 369) - Frydman Ultrasoft 4.5 catheters. Only patients offered ET in the randomized cycle were included (Group 1 = 363 and Group 2 = 340). Patients did not change groups after catheter allocation. Statistical analysis was carried out using an unpaired t test or a chi square test as appropriate. Differences with P<0.05 were considered. RESULTS: A statistically significant difference in favor of the use of the Ultrasoft catheter was evident for parameters use of a tenaculum (19.8% vs. 5.9%) or a hysterometer (5.0% vs. 1.2%), presence of blood during post-ET inspection of the catheter (9.9% vs. 3.8%), and implantation rate (13.0% vs. 16.4%). Clinical pregnancy and delivery rates were comparable in both groups. CONCLUSION: Our results suggest that a softer catheter may help with difficult ETs. Softer catheters, as also reported by other authors, resulted in better implantation rates. PMID- 27203194 TI - Frozen-Thawed Embryo Transfer Success Rate is Affected by Age and Ovarian Response at Oocyte Aspiration Regardless of Blastomere Survival Rate. AB - OBJECTIVE: To identify the factors influencing the success of frozen-thawed embryo transfers, whether originating directly from current cycles or from their matching fresh cycles. METHODS: Analysis of 273 frozen-thawed embryo transfer cycles and their matching fresh embryo transfer cycles, with respect to maternal, embryological and clinical factors, comparing successful to unsuccessful cycles. RESULTS: The cumulative clinical pregnancy and live birth rates following fresh ET and corresponding FETs were 50.5% and 38.8%, respectively. No outcome measure differed between fresh and frozen ET's. Only maternal age, number of oocytes retrieved and fertilized, and number of cleaved embryos in the fresh cycle were correlated with a higher pregnancy or live birth rate in the FET cycle. None of the other parameters had any effect on the outcome. Pre-freezing embryo quality and blastomere survival rate had no effect on pregnancy/live birth rates. CONCLUSION: Clinical pregnancy and live birth rates of fresh and frozen ETs were not significantly different. The only parameters that affected FET success were those resulting from the patient's age and ovarian reserve at the time of oocyte aspiration. Post-thawing blastomere survival rate and type of endometrial preparation for FET did not affect the success rate. PMID- 27203195 TI - New Sequence Variations in Spermatogenesis Candidates Genes. AB - OBJECTIVE: The aim of this paper was to estimate the frequency and types of mutations in key candidate genes involved in spermatogenesis, and their potential role as a cause of azoospermia /cryptozoospermia. METHODS: The sequencing of the coding region of genes DBY, RBMY, DAZ, CDY and BPY2, excluding the promoter region, was performed in a series of 25 patients with azoospermia or severe oligozoospermia without AZF microdeletions. The exon 3 from the DAZL gene (DAL3) was also sequenced. The sequences obtained were analyzed by ProSeq, DnaSP v5 and compared with the database using Blastn and tblastx. RESULTS: 16 of the 25 patients showed some type of variants, such as transversions, transitions, deletions and/or insertions in the DAZ, DAZL, CDY and RBMY genes. The mutated sequences had between 97 and 99% homology with the specific protein of every gene, except the DAZL (73%) and DAZ (94%) proteins. CONCLUSION: The variants found have not been described previously, suggesting they could be mutations that might affect protein function. PMID- 27203196 TI - Sperm Selection Using Three Semen Processing Techniques. AB - OBJECTIVE: This study aimed to assess the efficiency, in terms of recovered motile spermatozoa with normal morphology, of three sperm selection techniques: migration- sedimentation (SS), swim-up from fresh semen (SF), and swim-up from washed (SL) sperm. METHODS: Samples from 20 normozoospermic men were divided into three equal aliquots and processed in parallel. SS was performed in a Jondet tube, using 1 ml of semen and 2.5 ml of Human Tubal Fluid medium (HTF+10% Synthetic Serum Supplement, Irvine, USA). For SF, 1 ml of HTF was layered over 1 ml of fresh semen (SF). For SL, 1 ml of sperm was first centrifuged (300 g, 10 min) and the pellet resuspended in 1 ml of HTF; a second layer of HTF was placed on top. Migration time was 1h (SF and SL) and 1h30' for SS at 37 degrees C. After migration, 200 MUl were removed from the top layer (SF, SL) and from the central cone (SS). Concentration, morphology and motility were determined. RESULTS: Recovery rates were 25% for SS, 10.1% for SF and 4.5% for SL. SS recovery rate was significantly higher (P<0.01) than the two swim-up techniques. Total motility was statistically different (P<0.001), with 93.6% for SS, 91.2% for SF, and 77% for SL. Sperm morphology was similar between the three techniques (P= 0.12). CONCLUSION: SS is an efficient technique for the recovery of motile spermatozoa from native semen preparations and yielded better results than SF and SL. Routine use for assisted reproduction remains to be evaluated. PMID- 27203197 TI - Oocyte Quality in Patients with Increased FSH Levels. AB - OBJECTIVE: The present study consists of quality comparison among oocytes retrieved from women under 37 years old showing increased levels of FSH (prone to premature ovarian insufficiency) and women at the same age with normal hormone levels. METHODS: Oocyte quality was accessed according to Lucinda L. Veeck parameters (1986) and the statistical analyses were carried out using Chisquared, SPSS for Windows 13.0 (SPSS, Inc., Chicago, IL). All pvalues were twotailed, and 95% confidence intervals (CIs) were calculated. A P value <0.05 was considered statistically significant. RESULTS: Eight morphologic changes variables were considered in the study and two of them showed statistically significant differences between cases and controls: granular cytoplasm (P=0.002) and presence of vacuoles (P=0.025), both more frequent among the study group patients. CONCLUSION: As a conclusion, patients with increased FSH levels presented oocytes with worst quality variables than controls. This can be an indicative of ovarian aging and can impact negatively on oocyte development into viable embryos. PMID- 27203198 TI - Letrozole Therapy for Obstructive Azoospermic Men before in vitro Fertilization (IVF) treatment with Percutaneous Epididymal Sperm Aspiration. AB - OBJECTIVE: The aim of this study was to report our preliminary experience regarding the use of letrozole in men with obstructive azoospermia (OA) undergoing percutaneous epididymal sperm aspiration (PESA) for in vitro fertilization treatment using intracytoplasmic sperm injection (ICSI), who had a very low sperm recovery upon PESA and unsuccessful ICSI. Our hypothesis was that letrozole therapy could improve testicular function by increasing serum gonadotropins and T levels, stimulate testicle germ cells and, most importantly, that it enhanced the motile sperm count at a second attempt. METHODS: We report on our preliminary experience with letrozole therapy in 11 men with OA, who failed to achieve pregnancy in the first PESA-ICSI and did not have spermatozoa cryopreserved for a second attempt. The patients received 3 months of letrozole at 2.5mg/day and underwent PESA-ICSI after 6.1+/-3.8 months. The patients were 48.6 +/- 9.6 years old, and underwent at least two PESA procedures. We evaluated the total motile sperm count per PESA samples, as the increases in serum FSH, LH, and T levels after treatment. RESULTS: All parameters increased significantly at 3 months following letrozole therapy for most patients. The total motile sperm count increased from 100 to 500% compared to the first PESA. CONCLUSION: Letrozole can be considered a reliable treatment to improve sperm recovery for men with OA undergoing PESA-ICSI cycles by increasing serum gonadotropins and testosterone (T) levels, and-most importantly-the motile sperm count. PMID- 27203199 TI - Endometriosis Affects Oocyte Morphology in Intracytoplasmic Sperm Injection Cycles? AB - OBJECTIVE: To identify associations between presence of endometriosis and oocyte defects, embryo developmental potential, and cycle outcomes. METHODS: This study looked into the impact of endometriosis on oocyte and embryo quality, and blastocyst formation probability. Endometriosis was also correlated with cycle characteristics. In order to avoid age-related bias, in the first analysis only patients aged 36 years or younger were included, and the cycles were split into endometriosis infertility cycles (n=431; 3172 oocytes) and other cycles (n=2510; 24480 oocytes). RESULTS: The number of retrieved oocytes (10.6+/-21.2 vs. 14.6+/ 21.1, P<0.001), oocyte yield (68.1+/-20.0% vs. 70.6+/-19.6%, P=0.015), and embryos obtained (6.1+/-4.43 vs. 7.8+/-5.12, P<0.001) were lower among patients with endometriosis. Implantation rates (28.1%+/-38.9% vs. 33.9+/-42.7, P<0.001) were lower among patients with endometriosis, but fertilization, pregnancy, miscarriage and cycle cancelation rates were not different. There was a significant increase in the incidence of extra-cytoplasmic, but not intra cytoplasmic, oocyte defects among patients with endometriosis. The quality of embryos (45.3% vs. 47.3%, P=0.037) collected from patients with endometriosis was lower, but blastocyst formation rates were unaltered. CONCLUSION: A possible explanation for the lower implantation rates seen in patients with endometriosis is the poorer quality of the oocytes and embryos observed in this group of patients. PMID- 27203201 TI - Is Three a Crowd in Reproduction? (The Authorization of Mitochondrial Donation in the UK). AB - Regulations recently passed in the UK to allow mitochondrial donation through artificial reproductive techniques have heated up the debate about this procedure, which in the near future may be extended to other parts of the world. Detractors of mitochondrial donation invoke the excessive risks inherent to the very novelty of the procedure and the lack of knowledge of its consequences. In the ethical and legal context, the main concerns relate to motherhood determination, the notion of social individuality, its association with genetic manipulation and all the issues accompanying it, the risk of opening the door to more dangerous practices, the potential discrimination toward existing individuals suffering with mitochondrial diseases, the fact that the same outcome - preventing the transmission of mitochondrial diseases - can be achieved by means of less risky procedures, and the modification of the genetic pool of humanity. However, most of the underlined risks are more uncertain than actual, and, indeed, natural to every new technique. Considering the major benefits offered by the procedure, and as long as we act under the auspices of the principles of precaution and prevention, there are no obstacles to the transference of mitochondrial material through artificial reproductive techniques. PMID- 27203200 TI - Ewe Ovarian Tissue Vitrification: A Model for the Study of Fertility Preservation in Women. AB - Emergency in vitro fertilization followed by embryo vitrification is one feasible fertility preservation option for cancer patients. However, its clinical application has several limitations. Hormonal stimulation delays the initiation of oncotherapy and it is contraindicated in hormone-sensitive cancers or for use in pre-pubertal females. Vitrification of ovarian cortical tissue prior to the start of cancer treatment could be utilized for autotransplantation or for in vitro maturation of follicles enclosed in ovarian tissue. Nevertheless, the main concern associated with autotransplantation is the risk of malignant cell re introduction to the patient, which is non-existent with the use of follicular in vitro culture. Since obtaining ovarian tissues from women for research is challenging and experimental studies are difficult to complete due to ethical issues, exploring the alternative usage of animal models for fertility preservation may provide beneficial insight into the prospects of follicular culture as an alternative for fertility restoration following ovarian tissue vitrification. Similarities between ewe and human ovary structures, as well as in ovarian follicular development dynamics, make the ewe a possible animal model for the study of female fertility preservation. As vitrification of ovarian tissue has the potential to cryopreserve preantral ovarian follicles, the present review will describe the progress of ovarian tissue vitrification studies completed in ewes. PMID- 27203202 TI - Uterus Didelphys with Obstructed Hemivagina and Ipsilateral Renal Agenesis (OHVIRA Syndrome). AB - This paper aimed to report a series of 19 cases of uterus didelphys associated with obstructed hemivagina and ipsilateral renal agenesis. This retrospective descriptive observational study included the medical records of 19 patients seen at the Endocrinology Gynecology Sector of the Obstetrics and Gynecology Department of the Federal University of Parana, and focused on clinical data, complementary exams, patient management, and follow-up. From the 229 patients with genital anomalies seen between 1984 and 2009, 19 (8.3%) were diagnosed with uterus didelphys with vaginal septum and renal agenesis. The patients had a median age of +/-16.3 years. Eight subjects (42.6 %) reported abdominal pain; two of them (0.1%) had pelvic masses and seven (36.8%) had dysmenorrhea. Blood retention was confirmed by ultrasound and/ or magnetic resonance imaging of the pelvis, which revealed the existence of a duplicated uterus of the didelphys type with a cystic mass containing old blood obliterating the hemivagina. Urinary tract examination revealed the existence of ipsilateral renal agenesis. Unusual manifestations such as associated infection and rupture of the vaginal septum during sexual intercourse were also reported. The prevalence of uterus didelphys associated with obstructed hemivagina and ipsilateral renal agenesis was 8.3% in a series of 229 genital anomalies. The observance of clinical features is essential for the early identification of the syndrome and the adequate management of the patients. PMID- 27203203 TI - Embryos from in Vitro Maturation (IVM) Technique Can Be Successfully Vitrified Resulting in the Birth of a Healthy Child. AB - IVM can be an advantageous technique when applied to PCOS (Polycystic Ovarian Syndrome) patients. The oocytes are retrieved from antral follicles of non stimulated ovaries, specially preventing hyperstimulation syndrome. Apart from its role as a reproductive treatment, IVM has emerged as a promising tool for emergency fertility preservation, since it can be performed flexibly in either follicular or luteal phase. A 34-year-old patient with PCOS, high body mass index and tubal factor was submitted twice to IVM treatment. Her husband has low count spermatozoa. The first IVM cycle was in 2009, she transferred 3 fresh embryos and got pregnant giving birth to a healthy boy weighing 3.3 kg. In 2013, the patient returned for another IVM cycle and the embryos had to be vitrified because she failed to develop an adequate endometrium for transfer. In the next cycle, the endometrium was prepared using estrogen and progesterone and the two best embryos were warmed up and transferred. She became pregnant and after 36 weeks gave birth to a healthy girl weighing 2.7 kg. She still has four embryos left to transfer. IVM may be an alternative technique to be considered when dealing with PCOS patients. Although clinical outcomes are currently inferior when compared with conventional hormone driven ART (Artificial Reproductive Techniques), it does apply in some cases while preventing hyperstimulation risks. Thus, embryos obtained by IVM can also be vitrified with successful outcomes. PMID- 27203204 TI - Maternal exposure to ambient PM2.5 exaggerates fetal cardiovascular maldevelopment induced by homocysteine in rats. AB - Maternal exposure to airborne particulate matter with aerodynamic diameter <2.5 um (PM2.5 ) during pregnancy and lactation periods is associated with filial congenital cardiovascular diseases. This study aimed to investigate the toxic effects of maternal exposure to ambient levels of PM2.5 on filial cardiovascular maldevelopment induced by homocysteine. Using a 2 * 2 factorial design, rats were randomized into four groups and were exposed to ambient PM2.5 or filtered air (FA) throughout the pregnancy and lactation periods coupled with the administration of either homocysteine (HCY) or normal saline (NS) daily from gestation days 8-10. Morphological changes in the heart, myocardial apoptosis, expressions of cardiac progenitor transcriptional factors, and levels of cytokines were investigated in the offspring. The apoptosis-like changes in the myocardium were seen in the FA plus HCY-treated group and more obviously in the PM2.5 plus HCY-treated group, which was in accordance with an increased myocardial apoptosis rate in the two groups. PM2.5 exposure resulted in significantly decreased Nkx2-5 protein level and GATA4 and Nkx2-5 mRNA expressions, and significantly increased TNF-alpha and IL-1beta levels. There were significant interactions between PM2.5 exposure and HCY-treatment that PM2.5 exposure reduced Nkx2-5 protein levels and GATA4 and Nkx2-5 mRNA expressions in the HCY-treated groups. These results suggest that maternal exposure to PM2.5 , even at the ambient levels in urban regions in China, exaggerates filial cardiovascular maldevelopment induced by HCY in a murine model, exacerbating structural abnormalities in the filial cardiac tissue, which is possibly associated with oxidative stress and reduced GATA4 and Nkx2-5 transcription factor expressions. (c) 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 877-889, 2017. PMID- 27203205 TI - Transient liver elastography in unsedated control children: Impact of age and intercurrent illness. AB - AIM: Transient elastography (TE) is a rapid, non-invasive, reproducible assessment of liver fibrosis by liver stiffness measurement (LSM). Uncertainty remains regarding utility in children, unsedated and <6 years of age. The importance of general health at the time of study has not been addressed. We report our experience of TE in unsedated control children, impact of intercurrent illness and using new published reliability criteria. METHODS: From April 2011 to March 2013, 173 studies were performed in unsedated, healthy control children and children with intercurrent illness without detectable liver disease presenting to the Royal Children's Hospital, Brisbane, Australia. LSM reliability was assessed using interquartile range/median (IQR/M <= 30%) of 10 valid measurements. RESULTS: A total of 123 (F:M, 52:71) of 173 studies (71.1%) gave reliable results. In children 0-2 years reliability was 36%, and >2 years reliable results were obtained in ~80%. LSM increased with age; 0-2 years (3.5 +/- 0.5 kPa), 3-5 years (3.8 +/- 0.3 kPa) and 6-11 years (4.1 +/- 0.2 kPa) with healthy older children 12-18 years similar to adults (4.5 +/- 0.2 kPa). LSM did not vary with gender (female, 4.5 +/- 0.2 vs. male, 4.8 +/- 0.2 kPa). Children with intercurrent, non-hepatological illnesses had higher LSM (5.2 +/- 0.2 kPa (range, 2.8-11.1 kPa)) compared to healthy children ((4.1 +/- 0.1 kPa, range, 2.1-6.3 kPa); P = 0.0001). CONCLUSIONS: TE in unsedated children is feasible from infancy but most reliable after 2 years. Intercurrent illness increases LSM; hence, study context is important when interpreting results. PMID- 27203206 TI - Clinical value of fluorine-18 2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography in penile cancer. AB - PurposeThis study investigated the value of Fluorine-18 2-fluoro-2-deoxy-D glucose (FDG) positron emission tomography (PET)/computed tomography (CT) imaging in the management of patients with advanced penile cancer.Patients and MethodsBetween January 2009 and August 2012, 48 patients with penile cancer at our center underwent FDG-PET/CT after CT (n=39) or magnetic resonance imaging (MRI; n=9). The accuracy of FDG-PET/CT was assessed with both organ-based and patient-based analyses. FDG-PET/CT findings were validated by either biopsy or serial CT/MRI. Clinician questionnaires performed before and after FDG-PET/CT evaluated whether the scan results affected management.ResultsOne hundred fifteen individual lesions were evaluable in 42 patients for the organ-based analysis. Overall sensitivity was 85% and specificity was 86%. In the patient-based analysis, overall sensitivity and specificity were 82% and 93%, respectively. Pre and post-PET surveys showed that FDG-PET/CT detected more malignant diseases than CT/MRI in 33% patients. Planned treatments were changed in 57% patients after FDG-PET/CT scan.ConclusionFDG-PET/CT has good sensitivity and specificity in the detection of metastatic penile cancer. It provides more diagnostic information to enhance clinical management than CT/MRI. PMID- 27203210 TI - Pulmonary fibrosis in a mouse model of sarcoid granulomatosis induced by booster challenge with Propionibacterium acnes. AB - Pulmonary fibrosis (PF) associated with chronic sarcoidosis remains poorly understood, and no experimental model is currently available for this condition. Previous studies have shown that Propionibacterium acnes (PA) was associated with sarcoidosis and induced granuloma formation in mice. Here, we investigated whether repeated challenge with PA induces persistent inflammation leading to sarcoidosis followed by PF in mice. Specifically, C57BL/6 mice were inoculated intraperitoneally and subjected to intratracheal challenge with PA, and then were booster-challenged with either PA or phosphate-buffered saline on day 28. Inflammation, granulomata, and features of fibrosis were evaluated every 7 days until day 70. Complete remission of lung granulomata was apparent on day 42 in the sarcoid-remission group. However, granulomata was present from days 21 to 70 in mice that received PA boosting. Inflammatory cell counts and Th1 cytokine levels in lung lavage fluids were elevated up to day 70. Furthermore, fibrotic changes in the lungs were observed around granulomatous and peribronchovascular regions after PA boosting. Taken together, these findings suggest that development of PF following sarcoidosis may result from continuous PA infection and inflammation. Repeated boosting with PA to induce PF might be a useful model for future studies of sarcoidosis-associated PF. PMID- 27203208 TI - Inhibitors of Rho kinase (ROCK) signaling revert the malignant phenotype of breast cancer cells in 3D context. AB - Loss of polarity and quiescence along with increased cellular invasiveness are associated with breast tumor progression. ROCK plays a central role in actin cytoskeletal rearrangement. We used physiologically relevant 3D cultures of nonmalignant and cancer cells in gels made of laminin-rich extracellular matrix, to investigate ROCK function. Whereas expression levels of ROCK1 and ROCK2 were elevated in cancer cells compared to nonmalignant cells, this was not observed in 2D cultures. Malignant cells showed increased phosphorylation of MLC, corresponding to disorganized F-actin. Inhibition of ROCK signaling restored polarity, decreased disorganization of F-actin, and led to reduction of proliferation. Inhibition of ROCK also decreased EGFR and Integrinbeta1 levels, and consequently suppressed activation of Akt, MAPK and FAK as well as GLUT3 and LDHA levels. Again, ROCK inhibition did not inhibit these molecules in 2D. A triple negative breast cancer cell line, which lacks E-cadherin, had high levels of ROCK but was less sensitive to ROCK inhibitors. Exogenous overexpression of E cadherin, however, rendered these cells strikingly sensitive to ROCK inhibition. Our results add to the growing literature that demonstrate the importance of context and tissue architecture in determining not only regulation of normal and malignant phenotypes but also drug response. PMID- 27203207 TI - The retinal determination gene network: from developmental regulator to cancer therapeutic target. AB - Although originally identified for its function in Drosophila melanogaster eye specification, the Retinal Determination Gene Network (RDGN) is essential for the development of multiple organs in mammals. The RDGN regulates proliferation, differentiation and autocrine signaling, and interacts with other key signaling pathways. Aberrant expression of RDGN members such as DACH, EYA and SIX contributes to tumor initiation and progression; indeed, the levels of RDGN members are clinically prognostic factors in various cancer types. Stimulation or suppression of the activities of these crucial components can block cancer cell proliferation, prevent cancer stem cell expansion and even reverse the EMT process, thereby attenuating malignant phenotypes. Thus, cancer therapeutic interventions targeting RDGN members should be pursued in future studies. PMID- 27203211 TI - Age, serum 25-hydroxyvitamin D and vitamin D receptor (VDR) expression and function in peripheral blood mononuclear cells. AB - The relationship between age, vitamin D status, expression and functionality of the vitamin D receptor (VDR), and key genes in the vitamin D pathway in immune cells is unclear. We enrolled adults 50 to 69 years old (20 subjects) and 70+ (20 subjects) and measured: 1) 25(OH)D levels by liquid chromatography/mass spectrometry; and 2) mRNA expression of VDR, 1alpha-OHase, 1,25D3-MARRS, TREM-1, cathelicidin, RIG-I, and interferon-beta by qRT-PCR. Mean serum 25(OH)D was 30 +/ 4 ng/mL and was not associated with age. Baseline expression of VDR, 1alpha OHase, 1,25D3-MARRS, TREM-1, and RIG-I also did not differ by age; IFN-beta expression, however, was higher in the 70+ year old group. 25(OH)D3- and 1,25(OH)2D3-induced VDR, TREM-1 and cathelicidin expression were similar between age groups, as was LPS-induced expression of VDR and of 1alpha-OHase. Ligand induced 1,25D3-MARRS expression was higher in subjects >= 70 years. Serum 25(OH)D was inversely associated with LPS-stimulated VDR expression and with baseline or vitamin D-induced TREM-1 expression, adjusting for age, self-rated health, and functional status. In healthy adults >= 50 years, the expression and functionality of the VDR, 1alpha-OHase and key vitamin D pathway genes were not consistently associated with age. PMID- 27203212 TI - Organochloride pesticides induced hepatic ABCG5/G8 expression and lipogenesis in Chinese patients with gallstone disease. AB - BACKGROUND: Organochlorine pesticides (OCPs) are one kind of persistent organic pollutants. Although they are reported to be associated with metabolic disorders, the underlying mechanism is unclear. We explored the association of OCPs with gallstone disease and its influence on hepatic lipid metabolism. MATERIALS AND METHODS: OCPs levels in omentum adipose tissues from patients with and without gallstone disease between 2008 and 2011 were measured by GC-MS. Differences of gene expression involved in hepatic lipid metabolism and hepatic lipids content were compared in liver biopsies between groups with high and low level of OCPs. Using HepG2 cell lines, the influence on hepatic lipid metabolism by individual OCP was evaluated in vitro. RESULTS: In all patients who were from non occupational population, there were high levels of beta-hexachlorocyclohexane (beta-HCH) and p',p'-dichloroethylene (p',p'-DDE) accumulated in adipose tissues. Both beta-HCH and p', p'-DDE levels were significantly higher in adipose tissues from patients with gallstone disease (294.3+/- 313.5 and 2222+/- 2279 ng/g of lipid) than gallstone-free controls (282.7+/- 449.0 and 2025+/-2664 ng/g of lipid, P< 0.01) and they were strongly related with gallstone disease (P for trend = 0.0004 and 0.0138). Furthermore, higher OCPs in adipose tissue led to increase in the expression of hepatic cholesterol transporters ABCG5 and G8 (+34% and +27%, P< 0.01) and higher cholesterol saturation index in gallbladder bile, and induced hepatic fatty acids synthesis, which was further confirmed in HepG2 cells. CONCLUSIONS: OCPs might enhance hepatic secretion of cholesterol into bile via ABCG5/G8 which promoting gallstone disease as well as lipogenesis. PMID- 27203214 TI - Down-regulation of tensin2 enhances tumorigenicity and is associated with a variety of cancers. AB - Tensin family members, including tensin2 (TNS2), are present as major components of the focal adhesions. The N-terminal end of TNS2 contains a C1 region (protein kinase C conserved region 1) that is not found in other tensin members. Three isoforms of TNS2 have been identified with previous reports describing the shortest V3 isoform as lacking the C1 region. Although TNS2 is known to regulate cell proliferation and migration, its role in tumorigenicity is controversial. By gain-of-function overexpression approaches, results supporting either promotion or reduction of cancer cell tumorigenicity were reported. Here we report that the complete V3 isoform also contains the C1 region and describe the expression patterns of the three human TNS2 isoforms. By loss-of-function approaches, we show that silencing of TNS2 up-regulates the activities of Akt, Mek, and IRS1, and increases tumorigenicities in A549 and Hela cells. Using public database analyses we found that TNS2 is down-regulated in head and neck, esophageal, breast, lung, liver, and colon cancer. In addition, patients with low TNS2 expression showed poor relapse-free survival rates for breast and lung cancers. These results strongly suggest a role of tensin2 in suppressing cell transformation and reduction of tumorigenicity. PMID- 27203213 TI - Genetic landscape of T- and NK-cell post-transplant lymphoproliferative disorders. AB - Post-transplant lymphoproliferative disorders of T- or NK-cell origin (T/NK-PTLD) are rare entities and their genetic basis is unclear. We performed targeted sequencing of 465 cancer-related genes and high-resolution copy number analysis in 17 T-PTLD and 2 NK-PTLD cases. Overall, 377 variants were detected, with an average of 20 variants per case. Mutations of epigenetic modifier genes (TET2, KMT2C, KMT2D, DNMT3A, ARID1B, ARID2, KDM6B, n=11). and inactivation of TP53 by mutation and/or deletion(n=6) were the most frequent alterations, seen across disease subtypes, followed by mutations of JAK/STAT pathway genes (n=5). Novel variants, including mutations in TBX3 (n=3), MED12 (n=3) and MTOR (n=1), were observed as well. High-level microsatellite instability was seen in 1 of 14 (7%) cases, which had a heterozygous PMS2 mutation. Complex copy number changes were detected in 8 of 16 (50%) cases and disease subtype-specific aberrations were also identified. In contrast to B-cell PTLDs, the molecular and genomic alterations observed in T/NK-PTLD appear similar to those reported for peripheral T-cell lymphomas occurring in immunocompetent hosts, which may suggest common genetic mechanisms of lymphoma development. PMID- 27203215 TI - Effective elimination of adult B-lineage acute lymphoblastic leukemia by disulfiram/copper complex in vitro and in vivo in patient-derived xenograft models. AB - Disulfiram (DS), a clinically used drug to control alcoholism, has displayed promising anti-cancer activity against a wide range of tumors. Here, we demonstrated that DS/copper (Cu) complex effectively eliminated adult B-ALL cells in vitro and in vivo in patient-derived xenograft (PDX) humanized mouse models, reflected by inhibition of cell proliferation, induction of apoptosis, suppression of colony formation, and reduction of PDX tumor growth, while sparing normal peripheral blood mononuclear cells. Mechanistically, these events were associated with disruption of mitochondrial membrane potential and down regulation of the anti-apoptotic proteins Bcl-2 and Bcl-xL. Further analysis on B ALL patients' clinical characteristics revealed that the ex vivo efficacy of DS/Cu in primary samples was significantly correlated to p16 gene deletion and peripheral blood WBC counts at diagnosis, while age, LDH level, extramedullary infiltration, status post intensive induction therapy, immune phenotype, risk category, and Ph chromosome had no effect. Together, these findings indicate that disulfiram, particularly when administrated in combination with copper, might represent a potential repurposing agent for treatment of adult B-ALL patients, including those clinically characterized by one or more adverse prognostic factors. PMID- 27203216 TI - Down-regulation of ABCG2 and ABCB4 transporters in the placenta of rats exposed to cadmium. AB - As a maternal and developmental toxicant, cadmium (Cd) possesses weak penetrability through the placental barrier. However, the underlying mechanism remains unclear. To gain insight into the protein molecules associated with Cd toxicity in placenta and explore their roles in Cd transportation, a reproductive animal experiment was carried out using Sprague-Dawley rats. We performed proteomic analysis of the placenta by Difference Gel Electrophoresis (DIGE) combined with Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Tandem Mass Spectroscopy (MALDI-TOF/TOF MS). The DIGE assay identified 15 protein spots that were differentially expressed with a greater than 1.5-fold change in placenta of Cd-treated rats compared to the control rats. Based on the expression patterns and biological functions of the proteins, we selected the ABCG2 and ABCB4 transporter proteins for further analysis. Western blot analysis showed that Cd exposure could down-regulate the expression of ABCG2 and ABCB4 in the placenta. There was a negative dose-response relationship between Cd exposure and the expression of ABCG2 or ABCB4 protein. These results indicated that down regulation of ABCG2 and ABCB4 transporters may regulate Cd across through placenta and thus affect the in vivo toxic effect of Cd to fetus. PMID- 27203217 TI - Quantitation of TGF-beta proteins in mouse tissues shows reciprocal changes in TGF-beta1 and TGF-beta3 in normal vs neoplastic mammary epithelium. AB - Transforming growth factor-betas (TGF-betas) regulate tissue homeostasis, and their expression is perturbed in many diseases. The three isoforms (TGF-beta1, beta2, and -beta3) have similar bioactivities in vitro but show distinct activities in vivo. Little quantitative information exists for expression of TGF beta isoform proteins in physiology or disease. We developed an optimized method to quantitate protein levels of the three isoforms, using a Luminex(r) xMAP(r) based multianalyte assay following acid-ethanol extraction of tissues. Analysis of multiple tissues and plasma from four strains of adult mice showed that TGF beta1 is the predominant isoform with TGF-beta2 being ~10-fold lower. There were no sex-specific differences in isoform expression, but some tissues showed inter strain variation, particularly for TGF-beta2. The only adult tissue expressing appreciable TGF-beta3 was the mammary gland, where its levels were comparable to TGF-beta1. In situ hybridization showed the luminal epithelium as the major source of all TGF-beta isoforms in the normal mammary gland. TGF-beta1 protein was 3-8-fold higher in three murine mammary tumor models than in normal mammary gland, while TGF-beta3 protein was 2-3-fold lower in tumors than normal tissue, suggesting reciprocal regulation of these isoforms in mammary tumorigenesis. PMID- 27203219 TI - Intrapericardial bevacizumab safely and effectively treats malignant pericardial effusion in advanced cancer patients. AB - We evaluated the safety and efficacy of intrapericardial bevacizumab (BEV) for treating symptomatic malignant pericardiac effusion (MPCE) in seven advanced cancer patients. All patients had previously undergone multiple lines of systemic therapy. Each patient received paracentesis and intrapericardial infusions of 100 or 200 mg of BEV every two weeks. Systemic treatments for primary tumors continued for all patients during BEV treatment. Of the seven patients, three achieved a complete response, two achieved a partial response, and two showed no response with regard to MPCE after BEV infusion. The median overall survival time was 168 days (range, 22-224 days). In six of the seven patients, effusion did not recur before death. Toxicity associated with BEV treatment was mild and manageable in all patients. This study provides preliminary evidence that intrapericardial BEV may be an effective and safe treatment for MPCE in patients with advanced cancers. PMID- 27203221 TI - Aptamer-guided DNA tetrahedron as a novel targeted drug delivery system for MUC1 expressing breast cancer cells in vitro. AB - Mucin 1 (MUC1) is an important molecular target for cancer treatment because it is overexpressed in most adenocarcinomas. In this study, a new MUC1-targeted drug delivery system was assembled using an aptamer (Apt) that could recognize MUC1 and a DNA tetrahedron (Td) that could carry doxorubicin (Dox) within its DNA structure. The complex thus formed (Apt-Td) had an average size of 12.38 nm and was negatively charged. Similar to the MUC1 aptamer, the Apt-Td could preferentially bind with MUC1-positive MCF-7 breast cancer cells. A drug loading experiment revealed that each Apt-Td complex could carry approximately 25 Dox molecules. Moreover, Apt-Td selectively delivered Dox into the MUC1-positive breast cancer cells but reduced Dox uptake by the MUC1-negative control cells. Dox-loaded Apt-Td also induced a significantly higher cytotoxicity to the MUC1 positive cancer cells versus the MUC1-negative control cells in vitro (p<0.01). These results suggest that Apt-Td may potentially serve as a drug carrier in the targeted treatment of MUC1-expressing breast cancers. PMID- 27203222 TI - Assessment of Anisotropic Semiconductor Nanorod and Nanoplatelet Heterostructures with Polarized Emission for Liquid Crystal Display Technology. AB - Semiconductor nanorods can emit linear-polarized light at efficiencies over 80%. Polarization of light in these systems, confirmed through single-rod spectroscopy, can be explained on the basis of the anisotropy of the transition dipole moment and dielectric confinement effects. Here we report emission polarization in macroscopic semiconductor-polymer composite films containing CdSe/CdS nanorods and colloidal CdSe nanoplatelets. Anisotropic nanocrystals dispersed in polymer films of poly butyl-co-isobutyl methacrylate (PBiBMA) can be stretched mechanically in order to obtain unidirectionally aligned arrays. A high degree of alignment, corresponding to an orientation factor of 0.87, was achieved and large areas demonstrated polarized emission, with the contrast ratio I?/I? = 5.6, making these films viable candidates for use in liquid crystal display (LCD) devices. To some surprise, we observed significant optical anisotropy and emission polarization for 2D CdSe nanoplatelets with the electronic structure of quantum wells. The aligned nanorod arrays serve as optical funnels, absorbing unpolarized light and re-emitting light from deep-green to red with quantum efficiencies over 90% and high degree of linear polarization. Our results conclusively demonstrate the benefits of anisotropic nanostructures for LCD backlighting. The polymer films with aligned CdSe/CdS dot-in-rod and rod-in-rod nanostructures show more than 2-fold enhancement of brightness compared to the emitter layers with randomly oriented nanostructures. This effect can be explained as the combination of linearly polarized luminescence and directional emission from individual nanostructures. PMID- 27203220 TI - microRNA-7-5p inhibits melanoma cell proliferation and metastasis by suppressing RelA/NF-kappaB. AB - microRNA-7-5p (miR-7-5p) is a tumor suppressor in multiple cancer types and inhibits growth and invasion by suppressing expression and activity of the epidermal growth factor receptor (EGFR) signaling pathway. While melanoma is not typically EGFR-driven, expression of miR-7-5p is reduced in metastatic tumors compared to primary melanoma. Here, we investigated the biological and clinical significance of miR-7-5p in melanoma. We found that augmenting miR-7-5p expression in vitro markedly reduced tumor cell viability, colony formation and induced cell cycle arrest. Furthermore, ectopic expression of miR-7-5p reduced migration and invasion of melanoma cells in vitro and reduced metastasis in vivo. We used cDNA microarray analysis to identify a subset of putative miR-7-5p target genes associated with melanoma and metastasis. Of these, we confirmed nuclear factor kappa B (NF-kappaB) subunit RelA, as a novel direct target of miR-7-5p in melanoma cells, such that miR-7-5p suppresses NF-kappaB activity to decrease expression of canonical NF-kappaB target genes, including IL-1beta, IL-6 and IL 8. Importantly, the effects of miR-7-5p on melanoma cell growth, cell cycle, migration and invasion were recapitulated by RelA knockdown. Finally, analysis of gene array datasets from multiple melanoma patient cohorts revealed an association between elevated RelA expression and poor survival, further emphasizing the clinical significance of RelA and its downstream signaling effectors. Taken together, our data show that miR-7-5p is a potent inhibitor of melanoma growth and metastasis, in part through its inactivation of RelA/NF kappaB signaling. Furthermore, miR-7-5p replacement therapy could have a role in the treatment of this disease. PMID- 27203223 TI - UV-Induced Proton-Coupled Electron Transfer in Cyclic DNA Miniduplexes. AB - The excited-state dynamics of two cyclic DNA miniduplexes, each containing just two base pairs, are investigated using time-resolved infrared spectroscopy. As in longer DNA duplexes, intrastrand electron transfer induced by UV excitation triggers interstrand proton transfer in the alternating miniduplex containing two out-of-phase G.C base pairs. The resulting excited state decays on a time scale of several tens of picoseconds. This state is absent when one of the two G residues is substituted by 8-oxo-7,8-dihydroguanine, a modification that is suggested to disrupt base stacking, while maintaining base pairing. These findings demonstrate that a nucleobase tetramer arranged as two stacked base pairs accurately captures the interplay between intrastrand and interstrand decay channels. The similar signals seen in the miniduplexes and longer sequences suggest that excited states in the latter rapidly localize on two adjacent base pairs. PMID- 27203224 TI - Efficient production of succinic acid from Palmaria palmata hydrolysate by metabolically engineered Escherichia coli. AB - Succinic acid, a C4 dicarboxylic acid is used in many fields such as food, agriculture, pharmaceutical and polymer industries. In this study, microbial production of succinic acid from Palmaria palmata was investigated for the first time. In engineered Escherichia coli KLPPP, lactate dehydrogenase, pyruvate formate lyase, phosphotransacetylase-acetate kinase and pyruvate oxidase genes were deleted while phosphoenolpyruvate carboxykinase was overexpressed. The recombinant exhibited higher molar yield of succinic acid on galactose (1.20+/ 0.02mol/mol) than glucose (0.48+/-0.03mol/mol). The concentration and molar yield of succinic acid were 22.40+/-0.12g/L and 1.13+/-0.02mol/mol total sugar respectively after 72h dual phase fermentation from P. palmata hydrolysate which composed of glucose (12.57+/-0.17g/L) and galactose (18.03+/-0.10g/L). The results demonstrate that P. palmata red macroalgae biomass represents a novel and an economically alternative feedstock for biochemicals production. PMID- 27203225 TI - Cigarette smoking has a differential effect on the plasma level of clozapine in Taiwanese schizophrenic patients associated with the CYP1A2 gene -163A/C single nucleotide polymorphism. AB - OBJECTIVE: The efficacy of clozapine clearance has been shown to be associated with smoking and genetic polymorphism of CYP1A2. This study aims to investigate the effect of smoking on the plasma level of clozapine in Taiwanese schizophrenic patients and its relevance to the CYP1A2 gene -163A/C single nucleotide polymorphism. MATERIALS AND METHODS: A total of 143 hospitalized schizophrenic patients who had received clozapine therapy for at least 14 days were enrolled in this study. The trough plasma concentration of clozapine was measured with LC/MS/MS. The -163A/C variant in the CYP1A2 gene was identified by DNA sequencing and restriction fragment length polymorphism analysis. The effect of smoking on the clozapine level was examined by multiple linear regression analysis and its relation to the -163A/C variant of the CYP1A2 gene was analyzed using a general linear model with Bonferroni correction. RESULTS: Patients with smoking habits showed a significantly lower plasma level of clozapine than those without smoking habits (P=0.022) and the difference in clozapine levels between smokers and nonsmokers appeared to be significant in the individuals carrying the homozygous 163A allele (P=0.02). It was also found that nonsmokers carrying the -163A allele tended to have higher plasma levels of clozapine. This tendency was not found in the individuals with smoking habits. CONCLUSION: Cigarette smoking has a significant impact on the plasma level of clozapine in Taiwanese schizophrenic patients carrying the homozygous -163A allele in the CYP1A2 gene. Cigarette smoking may increase the clearance of clozapine in these patients. PMID- 27203226 TI - The COMT rs4680 polymorphism and suicide attempt in rural Shandong, China. AB - BACKGROUND: Suicide attempt is a major public health problem and are associated with genetic factors. This paired case-control study examined the association between the COMT gene rs4680 polymorphism and suicide attempts. METHODS: A case control study of 369 (117 men, 31.7%; mean age=44.1+/-13.3 years) suicide attempters and an equal number of controls without a lifetime history of suicide attempt matched on sex, age, and residence was carried out in rural Shandong, Eastern China. Demographics and psychiatric history were obtained through face-to face interviews. Blood samples were collected during interviews and the COMT gene rs4680 polymorphism was analyzed using the ligation detection reaction method. RESULTS: The G/G genotype was significantly more prevalent in female suicide attempters than their matched controls. Conditional logistic regression showed that the G/G genotype was significantly associated with an increased risk of suicide attempts only for women (odds ratio=2.3; 95% confidence interval: 1.2 4.2). CONCLUSION: The findings support an association between the COMT gene rs4680 polymorphism and suicide attempts only in women. Further research with larger samples is needed to explore the interactions of the COMT gene rs4680 polymorphism and sex and psychiatric disorders on suicide attempts. PMID- 27203228 TI - Situation awareness: when nurses decide to admit or not admit a person with mental illness as an involuntary patient. AB - AIM: This paper will explore the application of situation awareness in nursing to determine its suitability as a framework to study how the decision to admit or not admit a person as an involuntary patient is made. BACKGROUND: The decision by a specially qualified nurse to admit or not admit a person to a mental health facility against their will remains a central component of contemporary mental health legislation. The decision has an impact on a person's autonomy and human rights. Conversely, the decision to admit may facilitate urgent assessment and treatment and ensure the safety of the individual and others. Research highlights that decision-making in this context is challenging due to the multiple information sources and often incomplete information available to the clinician. Situation awareness is a concept used to explain how practitioners identify, use and make meaning of a multitude of factors and elements relevant to their practice. DESIGN: Discussion paper. DATA SOURCES: A search of terms related to situation awareness and mental health nursing was conducted in the period 2000 - present. IMPLICATIONS FOR NURSING: Exploring nurses decision-making using a situation awareness framework provides for a more nuanced understanding of nurses knowledge and skill when deciding to admit or not a person as an involuntary patient. CONCLUSION: The concept of situation awareness provides a framework to better understand the decision-making process associated with the involuntary admission decision. PMID- 27203229 TI - Heating Rate Sensitive Multi-Shape Memory Polypropylene: A Predictive Material. AB - Here we report on a novel type of smart material that is capable of specifically responding to the changing rate of an environmental signal. This is shown on the example of lightly cross-linked syndiotactic polypropylene that reacts to a temperature increase by adapting its shape change according to the applied heating rate. In general, a material with such properties can be used to predict a system failure when used in a defined environment and is therefore called "predictive material". PMID- 27203227 TI - Increased tumor response to neoadjuvant therapy among rectal cancer patients taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. AB - BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are commonly used antihypertensive medications that have been reported to affect aberrant angiogenesis and the dysregulated inflammatory response. Because of such mechanisms, it was hypothesized that these medications might affect the tumor response to neoadjuvant radiation in patients with rectal cancer. METHODS: One hundred fifteen patients who were treated with neoadjuvant radiation at the University of Wisconsin (UW) between 1999 and 2012 were identified. Univariate analyses were performed with anonymized patient data. In a second independent data set, 186 patients with rectal cancer who were treated with neoadjuvant radiation at the Queen's Medical Center of the University of Hawaii (UH) between 1995 and 2010 were identified. These data were independently analyzed as before. Multivariate analyses were performed with aggregate data. RESULTS: Among patients taking ACEIs/ARBs in the UW data set, a significant 3 fold increase in the rate of pathologic complete response (pCR) to neoadjuvant therapy (52% vs 17%, P = .001) was observed. This finding was confirmed in the UH data set, in which a significant 2-fold-increased pCR rate (24% vs 12%, P = .03) was observed. Identified patient and treatment characteristics were otherwise balanced between patients taking and not taking ACEIs/ARBs. No significant effect was observed on pCR rates with other medications, including statins, metformin, and aspirin. Multivariate analyses of aggregate data identified ACEI/ARB use as a strong predictor of pCR (odds ratio, 4.02; 95% confidence interval, 2.06-7.82; P < .001). CONCLUSIONS: The incidental use of ACEIs/ARBs among patients with rectal cancer is associated with a significantly increased rate of pCR after neoadjuvant treatment. Cancer 2016;122:2487-95. (c) 2016 American Cancer Society. PMID- 27203230 TI - Photochemical Reactions of the LOV and LOV-Linker Domains of the Blue Light Sensor Protein YtvA. AB - YtvA is a blue light sensor protein composed of an N-terminal LOV (light-oxygen voltage) domain, a linker helix, and the C-terminal sulfate transporter and anti sigma factor antagonist domain. YtvA is believed to act as a positive regulator for light and salt stress responses by regulating the sigmaB transcription factor. Although its biological function has been studied, the reaction dynamics and molecular mechanism underlying the function are not well understood. To improve our understanding of the signaling mechanism, we studied the reaction of the LOV domain (YLOV, amino acids 26-127), the LOV domain with its N-terminal extension (N-YLOV, amino acids 1-127), the LOV domain with its C-terminal linker helix (YLOV-linker, amino acids 26-147), and the YLOV domain with the N-terminal extension and the C-terminal linker helix (N-YLOV-linker, amino acids 1-147) using the transient grating method. The signals of all constructs showed adduct formation, thermal diffusion, and molecular diffusion. YLOV showed no change in the diffusion coefficient (D), while the other three constructs showed a significant decrease in D within ~70 MUs of photoexcitation. This indicates that conformational changes in both the N- and C-terminal helices of the YLOV domain indeed do occur. The time constant in the YtvA derivatives was much faster than the corresponding dynamics of phototropins. Interestingly, an additional reaction was observed as a volume expansion as well as a slight increase in D only when both helices were included. These findings suggest that although the rearrangement of the N- and C-terminal helices occurs independently on the fast time scale, this change induces an additional conformational change only when both helices are present. PMID- 27203231 TI - A novel ratiometric two-photon fluorescent probe for imaging of Pd(2+) ions in living cells and tissues. AB - Ratiometric two-photon fluorescent probes can not only eliminate interferences from environmental factors but also achieve deep-tissue imaging with improved spatial localization. To quantitatively track Pd(2+) in biosystems, herein, we reported a ratiometric two-photon fluorescent probe, termed as Np-Pd, which based on a D-pi-A-structure two-photon fluorophore of the naphthalimide derivative and deprotection of aryl propargyl ethers by palladium species. The probe Np-Pd displayed a more than 25-fold enhancement towards palladium species with high sensitivity and selectivity. Additionally, the probe Np-Pd was further used for fluorescence imaging of Pd(2+) ions in living cells and tissues under two-photon excitation (820nm), which showed large tissue-imaging depth (19.6-184.6MUm), and a high resolution for ratiometric imaging. PMID- 27203232 TI - A new fluorescence turn-on probe for biothiols based on photoinduced electron transfer and its application in living cells. AB - A new biothiol-selective fluorescent probe 1 based on photoinduced electron transfer (PET) mechanism was designed and synthesized. The UV-Vis absorption and fluorescent emission properties of probe 1 towards various analytes were studied in detail. The probe exhibited a large stokes shift (~200nm) after reacted with biothiols and could selectively detect cysteine (Cys) in dimethyl sulfoxide (DMSO)/H2O solution (9:1, v/v, 10mM phosphate buffer saline, pH3.5) over glutathione (GSH), homocysteine (Hcy) and other analytes with a detection limit of 0.117MUM. In addition, probe 1 responded well to GSH, Hcy and Cys in the same above solution with pH5.5 and got the detection limits of 0.151MUM, 0.128MUM and 0.037MUM, respectively. Probe 1 was of very low cytotoxicity and successfully applied for imaging of thiols in living cells. PMID- 27203234 TI - Benjamin F. Cravatt. PMID- 27203235 TI - [Treatment Methods for Patients with Dupuytren's Disease in Switzerland]. AB - BACKGROUND/OBJECTIVE: The objective of this study was to investigate what treatment options are currently used in Switzerland for Dupuytren's disease. Furthermore, regional preferences and treatment differences based on surgeon experience were analysed. MATERIAL AND METHODS: In this survey, an electronic questionnaire was sent to all members of the Swiss Society for Hand Surgery. Participants were asked to indicate their current treatment methods for Dupuytren's disease. In addition, 8 standard patient cases were presented to identify the preferred treatment option. Furthermore, sociodemographic data of the participants were gathered. RESULTS: In total, 70 questionnaires were completed, corresponding to a response rate of 34%. Fasciectomy is performed by 94% of participants, while 59% inject collagenase in certain cases, 40% perform open fasciotomy, and 24% carry out percutaneous needle aponeurotomy if the indication is given. 20% of responders offer one of these techniques, 50% offer 2, 23% offer 3, and 7% offer all 4 treatment techniques. In the case of isolated metacarpophalangeal joint contracture, 51% of participants inject collagenase, whereas fasciectomy is preferred for the treatment of proximal interphalangeal joint contractures or in cases of recurrence. In German-speaking Switzerland, the treatment strategy has changed towards applying collagenase injections in the past 5 years. In this part of the country, 83% of surgeons now use more collagenase than 5 years ago, whereas only 33% of surgeons in French-speaking Switzerland have changed their treatment strategy in favour of collagenase injections (p=0.027). Surgeons with less than 10 years of experience apply more collagenase than their more experienced colleagues (79 vs. 54%, p=0.131). CONCLUSIONS: In Switzerland, fasciectomy is the preferred option for treating patients with Dupuytren's disease. In recent years, however, collagenase injection has become more and more popular. More research is needed to define guidelines for the treatment of patients with Dupuytren's disease considering the effectiveness of the different treatment options and regional preferences. PMID- 27203233 TI - Transient spectra study on photo-dynamics of curcumin. AB - A novel mechanism of DNA damage induced by photosensitized curcumin (Cur) was explored using laser flash photolysis, pulse radiolysis and gel electrophoresis. Cur neutral radical (Cur) was confirmed as an identical product in photo sensitization of Cur by laser flash photolysis and pulse radiolysis. A series of reaction rate constants between Cur and nucleic acid bases/nucleotides were determined by pulse radiolysis. Gel electrophoresis was carried out to investigate damage induced by photosensitized Cur to biologically active DNA. The results indicate that the damage to DNA may be caused by Cur produced from the photosensitization of Cur. PMID- 27203236 TI - [A Simple Surgical Procedure to Correct Overlapping of the Fifth Toe in Children]. PMID- 27203237 TI - Computational Identification of Genomic Features That Influence 3D Chromatin Domain Formation. AB - Recent advances in long-range Hi-C contact mapping have revealed the importance of the 3D structure of chromosomes in gene expression. A current challenge is to identify the key molecular drivers of this 3D structure. Several genomic features, such as architectural proteins and functional elements, were shown to be enriched at topological domain borders using classical enrichment tests. Here we propose multiple logistic regression to identify those genomic features that positively or negatively influence domain border establishment or maintenance. The model is flexible, and can account for statistical interactions among multiple genomic features. Using both simulated and real data, we show that our model outperforms enrichment test and non-parametric models, such as random forests, for the identification of genomic features that influence domain borders. Using Drosophila Hi-C data at a very high resolution of 1 kb, our model suggests that, among architectural proteins, BEAF-32 and CP190 are the main positive drivers of 3D domain borders. In humans, our model identifies well-known architectural proteins CTCF and cohesin, as well as ZNF143 and Polycomb group proteins as positive drivers of domain borders. The model also reveals the existence of several negative drivers that counteract the presence of domain borders including P300, RXRA, BCL11A and ELK1. PMID- 27203239 TI - Comparative seed germination traits in alpine and subalpine grasslands: higher elevations are associated with warmer germination temperatures. AB - Seed germination traits in alpine grasslands are poorly understood, despite the sensitivity of these communities to climate change. We hypothesise that germination traits predict species occurrence along the alpine-subalpine elevation gradient. Phylogenetic comparative analyses were performed using fresh seeds of 22 species from alpine and subalpine grasslands (1600-2400 m) of the Cantabrian Mountains, Spain (43 degrees N, 5 degrees W). Laboratory experiments were conducted to characterise germinability, optimum germination temperature and effect of cold and warm stratification on dormancy breaking. Variability in these traits was reduced by phylogenetic principal component analysis (phyl.PCA). Phylogenetic generalised least squares regression (PGLS) was used to fit a model in which species average elevation was predicted from their position on the PCA axes. Most subalpine species germinated in snow-like conditions, whereas most alpine species needed accumulation of warm temperatures. Phylogenetic signal was low. PCA1 ordered species according to overall germinability, whilst PCA2 ordered them according to preference for warm or cold germination. PCA2 significantly predicted species occurrence in the alpine-subalpine gradient, as higher elevation species tended to have warmer germination preferences. Our results show that germination traits in high-mountain grasslands are closely linked to the alpine-subalpine gradient. Alpine species, especially those from stripped and wind-edge communities, prefer warmer germination niches, suggesting that summer emergence prevents frost damage during seedling establishment. In contrast, alpine snowfield and subalpine grassland plants have cold germination niches, indicating that winter emergence may occur under snow to avoid drought stress. PMID- 27203238 TI - Late Pregnancy is a Critical Period for Changes in Phosphorylated Mitogen Activated Protein Kinase/Extracellular Signal-Regulated Kinase 1/2 in Oxytocin Neurones. AB - The physiological demands of parturition and lactation lead to the increased pulsatile release of oxytocin (OT) into the circulation from the neurohypophysial axons of OT neurones in the supraoptic (SON) and paraventricular (PVN) nuclei. These states of increased OT release are accompanied by a significant plasticity in magnocellular OT neurones and their synaptic connections, and many of these changes require activation of a central OT receptor. The mitogen-activated protein kinase/extracellular signal-regulated kinase pathway (MAPK/ERK) is assumed to be up-regulated in the PVN during lactation, and many of the effects of OT in peripheral and brain tissue are mediated through a MAPK/ERK pathway. The present study investigated whether this pathway is altered in the SON and PVN during late pregnancy [embryonic day (E)20-21], which is a critical period for OT plasticity induction, and for lactation, when plastic changes are sustained. Based on immunoreactivity for phosphorylated ERK1/2 (pERK1/2), the results suggest an enhanced activation of MAPK/ERK pathway in OT neurones specifically during late pregnancy in both the SON and PVN. Although immunoblots from the SON confirm this pregnancy-associated up-regulation in late pregnancy, they also suggest enhancement into lactation as well. Together, the results suggest an important role for the MAPK/ERK pathway during reproductive changes in the SON and PVN. PMID- 27203241 TI - Correction: Cognitive Test Scores in UK Biobank: Data Reduction in 480,416 Participants and Longitudinal Stability in 20,346 Participants. AB - [This corrects the article DOI: 10.1371/journal.pone.0154222.]. PMID- 27203242 TI - Correction: Investigating the Proton Donor in the NO Reductase from Paracoccus denitrificans. AB - [This corrects the article DOI: 10.1371/journal.pone.0152745.]. PMID- 27203240 TI - The Effects of Cigarette Smoke Condensate and Nicotine on Periodontal Tissue in a Periodontitis Model Mouse. AB - Cigarette smoking is a major lifestyle-related risk factor for periodontal diseases. However, the pathophysiological role of cigarette smoking in periodontal disease has yet to be fully elucidated. Here we report that the systemic administration of cigarette smoke condensate or nicotine, which is the major ingredient of cigarette smoke, augmented alveolar bone loss. Concomitantly, the number of osteoclasts in periodontal tissues increased and the expression of receptor activator of nuclear factor kappaB ligand was upregulated at the ligated side in mice with periodontitis. Nicotine also attenuated alveolar bone repair after ligature removal. These observations highlight the destruction of periodontal tissue by smoking and the unfavorable clinical course of periodontal disease in patients with a cigarette smoking habit. The present study demonstrates that periodontal disease models are useful for elucidating the pathogenesis of cigarette smoking-related periodontal diseases. PMID- 27203243 TI - Variation between Hospitals with Regard to Diagnostic Practice, Coding Accuracy, and Case-Mix. A Retrospective Validation Study of Administrative Data versus Medical Records for Estimating 30-Day Mortality after Hip Fracture. AB - BACKGROUND: The purpose of this study was to assess the validity of patient administrative data (PAS) for calculating 30-day mortality after hip fracture as a quality indicator, by a retrospective study of medical records. METHODS: We used PAS data from all Norwegian hospitals (2005-2009), merged with vital status from the National Registry, to calculate 30-day case-mix adjusted mortality for each hospital (n = 51). We used stratified sampling to establish a representative sample of both hospitals and cases. The hospitals were stratified according to high, low and medium mortality of which 4, 3, and 5 hospitals were sampled, respectively. Within hospitals, cases were sampled stratified according to year of admission, age, length of stay, and vital 30-day status (alive/dead). The final study sample included 1043 cases from 11 hospitals. Clinical information was abstracted from the medical records. Diagnostic and clinical information from the medical records and PAS were used to define definite and probable hip fracture. We used logistic regression analysis in order to estimate systematic between-hospital variation in unmeasured confounding. Finally, to study the consequences of unmeasured confounding for identifying mortality outlier hospitals, a sensitivity analysis was performed. RESULTS: The estimated overall positive predictive value was 95.9% for definite and 99.7% for definite or probable hip fracture, with no statistically significant differences between hospitals. The standard deviation of the additional, systematic hospital bias in mortality estimates was 0.044 on the logistic scale. The effect of unmeasured confounding on outlier detection was small to moderate, noticeable only for large hospital volumes. CONCLUSIONS: This study showed that PAS data are adequate for identifying cases of hip fracture, and the effect of unmeasured case mix variation was small. In conclusion, PAS data are adequate for calculating 30-day mortality after hip-fracture as a quality indicator in Norway. PMID- 27203246 TI - An international perspective on outreach. PMID- 27203244 TI - Essential Roles of Cyclin Y-Like 1 and Cyclin Y in Dividing Wnt-Responsive Mammary Stem/Progenitor Cells. AB - Cyclin Y family can enhance Wnt/beta-catenin signaling in mitosis. Their physiological roles in mammalian development are yet unknown. Here we show that Cyclin Y-like 1 (Ccnyl1) and Cyclin Y (Ccny) have overlapping function and are crucial for mouse embryonic development and mammary stem/progenitor cell functions. Double knockout of Ccnys results in embryonic lethality at E16.5. In pubertal development, mammary terminal end buds robustly express Ccnyl1. Depletion of Ccnys leads to reduction of Lrp6 phosphorylation, hampering beta catenin activities and abolishing mammary stem/progenitor cell expansion in vitro. In lineage tracing experiments, Ccnys-deficient mammary cells lose their competitiveness and cease to contribute to mammary development. In transplantation assays, Ccnys-deficient mammary cells fail to reconstitute, whereas constitutively active beta-catenin restores their regeneration abilities. Together, our results demonstrate the physiological significance of Ccnys mediated mitotic Wnt signaling in embryonic development and mammary stem/progenitor cells, and reveal insights in the molecular mechanisms orchestrating cell cycle progression and maintenance of stem cell properties. PMID- 27203247 TI - Mutant mouse model stutters in squeaks. PMID- 27203248 TI - Preventing mussel loss. PMID- 27203250 TI - Dirty mice might make better models. PMID- 27203251 TI - Controlling mouse metabolism by radio waves. PMID- 27203252 TI - A new research path into attention disorders. PMID- 27203253 TI - The Concordant on Openness and its benefits to animal research. PMID- 27203256 TI - Adapting to change: The USDA's 'teachable moment'. PMID- 27203255 TI - The peculiar physiology of the python. PMID- 27203257 TI - Response to Protocol Review Scenario: 'Borrowing' is not an acceptable practice. PMID- 27203258 TI - Sharing animals across protocols. PMID- 27203259 TI - Response to Protocol Review Scenario: An IACUC reviews much more than training. PMID- 27203260 TI - Response to Protocol Review Scenario: Stitching together multiple protocols creates confusion. PMID- 27203261 TI - Considerations for aerobic exercise paradigms with rodent models. PMID- 27203263 TI - Care of Mastomys in the laboratory. AB - Mastomys rodents occupy a valuable niche in biomedical research, but there is very little published information regarding how to care for them in the laboratory. Here we provide information about the physical and behavioral characteristics of this unusual laboratory rodent, its taxonomic history, common diseases that affect it, and its use in research. We also provide housing recommendations based upon almost 15 years of experience successfully maintaining a colony of Mastomys coucha at our institution. PMID- 27203265 TI - The power of storytelling. PMID- 27203264 TI - Treatment and re-characterization of mouse obstructive genitourinary syndrome. AB - We aimed to characterize and to explore a treatment for a condition in which male mice exhibited a solid bulge in the preputial area and an inability to breed. Twenty-seven mice from several animal housing institutions in Spain were included in this study for microbiological and pathological characterization of this condition. The condition mostly affected breeding animals and was associated with the C57BL/6J genetic background. A solid, yellowish-white substance was found inside the prepuce, which displaced the penis cranially, preventing its externalization and limiting the animal's capacity to breed. This pattern was almost identical to that of post-coital vaginal plugs, suggesting that the blocking substance originated from ejaculate. Opposite to what was suggested in previous publications, the penis was completely intact in all of the cases, with no signs of mutilation or wounds. Based on our findings, we developed a surgical technique to clear the prepuce and recover breeding performance, which we tested in 15 other mice with the condition. We eliminated the blocking substance and recurrence of the condition by surgically opening the prepuce, and most of the animals recovered fertility. PMID- 27203266 TI - World Day for Laboratory Animals. PMID- 27203267 TI - Tools and techniques for maintaining catheter patency. PMID- 27203268 TI - Choice of laboratory animal diet influences intestinal health. PMID- 27203269 TI - Mechanisms of osteocyte stimulation in osteoporosis. AB - Experimental studies have shown that primary osteoporosis caused by oestrogen deficiency results in localised alterations in bone tissue properties and mineral composition. Additionally, changes to the lacunar-canalicular architecture surrounding the mechanosensitive osteocyte have been observed in animal models of the disease. Recently, it has also been demonstrated that the mechanical stimulation sensed by osteocytes changes significantly during osteoporosis. Specifically, it was shown that osteoporotic bone cells experience higher maximum strains than healthy bone cells after short durations of oestrogen deficiency. However, in long-term oestrogen deficiency there was no significant difference between bone cells in healthy and normal bone. The mechanisms by which these changes arise are unknown. In this study, we test the hypothesis that complex changes in tissue composition and lacunar-canalicular architecture during osteoporosis alter the mechanical stimulation of the osteocyte. The objective of this research is to employ computational methods to investigate the relationship between changes in bone tissue composition and microstructure and the mechanical stimulation of osteocytes during osteoporosis. By simulating physiological loading, it was observed that an initial decrease in tissue stiffness (of 0.425GPa) and mineral content (of 0.66wt% Ca) relative to controls could explain the mechanical stimulation observed at the early stages of oestrogen deficiency (5 weeks post-OVX) during in situ bone cell loading in an oestrogen-deficient rat model of post-menopausal osteoporosis (Verbruggen et al., 2015). Moreover, it was found that a later increase in stiffness (of 1.175GPa) and mineral content (of 1.64wt% Ca) during long-term osteoporosis (34 weeks post-OVX), could explain the mechanical stimuli previously observed at a later time point due to the progression of osteoporosis. Furthermore, changes in canalicular tortuosity arising during osteoporosis were shown to result in increased osteogenic strain stimulation, though to a lesser extent than has been observed experimentally. The findings of this study indicate that changes in the extracellular environment during osteoporosis, arising from altered mineralisation and lacunar-canalicular architecture, lead to altered mechanical stimulation of osteocytes, and provide an enhanced understanding of changes in bone mechanobiology during osteoporosis. PMID- 27203270 TI - Taming Lanthanide-Centered Upconversion at the Molecular Level. AB - Considered at the beginning of the 21th century as being incompatible with the presence of closely bound high-energy oscillators, lanthanide-centered superexcitation, which is the raising of an already excited electron to an even higher level by excited-state energy absorption, is therefore a very active topic strictly limited to the statistical doping of low-phonon bulk solids and nanoparticles. We show here that molecular lanthanide-containing coordination complexes may be judiciously tuned to overcome these limitations and to induce near-infrared (NIR)-to-visible (VIS)-light upconversion via the successive absorption of two low-energy photons using linear-optical responses. Whereas single-ion-centered excited-state absorption mechanisms remain difficult to implement in lanthanide complexes, the skillful design of intramolecular intermetallic energy-transfer processes operating in multimetallic architectures is at the origin of the recent programming of erbium-centered molecular upconversion. PMID- 27203271 TI - Symptom Clusters in Adults With Chronic Atrial Fibrillation. AB - BACKGROUND: Symptom clusters have not previously been explored among individuals with atrial fibrillation of any type. OBJECTIVE: The purpose of this study is to determine the number of symptom clusters present among adults with chronic atrial fibrillation and to explore sociodemographic and clinical factors potentially associated with cluster membership. METHODS: This was a cross-sectional secondary data analysis of 335 Australian community-dwelling adults with chronic (recurrent paroxysmal, persistent, or permanent) atrial fibrillation. We used self-reported symptoms and agglomerative hierarchical cluster analysis to determine the number and content of symptom clusters present. RESULTS: There were slightly more male (52%) than female participants, with a mean (SD) age of 72 (11.25) years. Three symptom clusters were evident, including a vagal cluster (nausea and diaphoresis), a tired cluster (fatigue/lethargy, weakness, syncope/dizziness, and dyspnea/breathlessness), and a heart cluster (chest pain/discomfort and palpitations/fluttering). We compared patient characteristics among those with all the symptoms in the cluster, those with some of the symptoms in the cluster, and those with none of the symptoms in the cluster. The only statistically significant differences were in age, gender, and the use of antiarrhythmic medications for the heart cluster. Women were more likely to have the heart symptom cluster than men were. Individuals with all of the symptoms in the heart cluster were younger (69.6 vs 73.7 years; P = .029) than those with none of the symptoms in the heart cluster and were more likely to be on antiarrhythmic medications. CONCLUSION: Three unique atrial fibrillation symptom clusters were identified in this study population. PMID- 27203272 TI - A Multicenter Trial of a Shared Decision Support Intervention for Patients and Their Caregivers Offered Destination Therapy for Advanced Heart Failure: DECIDE LVAD: Rationale, Design, and Pilot Data. AB - BACKGROUND: Shared decision making is important to ensure that patients receive therapies aligned with their goals and values. Based upon a detailed needs assessment with diverse stakeholders, pamphlet and video decision aids for destination therapy left ventricular assist devices (DT LVAD) were developed to help patients and their caregivers think through, forecast, and deliberate their options. These decision aids are the foundation of the Multicenter Trial of a Shared Decision Support Intervention for Patients and their Caregivers Offered Destination Therapy for End-Stage Heart Failure (DECIDE-LVAD) study, a multicenter, randomized trial aimed at understanding the effectiveness and implementation of a shared decision support intervention for patients considering DT LVAD. METHODS/DESIGN: A stepped-wedge randomized controlled trial was designed, guided by the RE-AIM framework and modeled after an effectiveness implementation hybrid type II design. Six DT LVAD programs from across the United States will participate. Primary outcomes include knowledge and values-treatment concordance. Patients with advanced heart failure who are being considered for DT LVAD and their caregivers are eligible with a target enrollment of 168 dyads. From August 2014 to January 2015, an acceptability and feasibility pilot study was performed, which clarified opportunities and challenges around decision support for DT LVAD and resulted in significant modifications to the DECIDE-LVAD study. DISCUSSION: Study findings will provide a foundation for implementing decision support interventions, including decision aids, with patients who have chronic progressive illness facing end-of-life decisions involving invasive, preference-sensitive therapy options. PMID- 27203273 TI - Factors Associated With 7-Day Rehospitalization After Heart Failure Admission. AB - BACKGROUND: Rehospitalizations within 7 days after discharge may reflect the quality of hospital care. OBJECTIVE: We examined factors associated with 7-day readmissions after discharge for heart failure (HF). METHODS: Using a matched pair case-control design, we examined health records for sociodemographic, clinical, and health system factors for patients with a primary diagnosis of HF (ICD-10 I50) discharged alive from all acute care hospitals in Calgary, Alberta, from 2004 to 2012. Logistic regression was used to identify variables associated with 7-day all-cause readmission. RESULTS: We included 382 patients, or 191 in matched pairs, with 41% of readmissions due to HF. Frailty (adjusted odds ratio [aOR], 2.30; 95% confidence interval [CI], 1.41-3.76) and attending physician as specialist (aOR, 2.10; 95% CI, 1.32-3.42) were associated with increased likelihood of readmission. Reduced likelihood of readmission was associated with documented instructions for follow-up with a family physician within 1 week of discharge (aOR, 0.56; 95% CI, 0.36-0.88). All 3 factors were easily abstracted from all patient records, including frailty, which was defined as all 3 of age older than 75 years, 3 or more comorbid conditions, and requiring assistance with activities of daily living. CONCLUSION: Very early readmission to hospital after HF admission is associated with 3 factors that may be easily identified in patient records. PMID- 27203274 TI - A Systematic Review of Tests Assessing Stroke Knowledge. AB - BACKGROUND: Accurate assessment of stroke knowledge (SK) is fundamental to the successful understanding of, monitoring of, and intervening to improve the SK of patients and the public. PURPOSE: The purpose of this study is to perform a systematic review of the existing SK tests and appraise their conceptual basis, feasibility, and psychometric properties. We conducted 2-step searching of MEDLINE, CINAHL, PsycINFO, and Scopus electronic databases from January 1, 2000, to December 31, 2014, to identify relevant SK tests for the appraisal. RESULTS: Our study found 59 SK tests, out of a total of 93 articles, with full content available that had been referred to in the published literature. Ten of them had been used in more than 1 study, and 2 (the Stroke Knowledge Test and the Stroke Action Test) of them have had at least 1 of their psychometric properties validated. Only 1 test (the Stroke Knowledge Test) was developed using rigorous methodology, covers a wide range of concepts, and met all feasibility criteria; however, its limitations include no articulated conceptual basis, inadequate internal consistency reliability (alpha = .65), and lack of some validated psychometric properties. CONCLUSIONS: Our study revealed that current available tools are not sufficiently able to accurately and reliably assess SK to promote stroke prevention and management. CLINICAL IMPLICATIONS: This study highlights the attention of applying current SK tests and need for revising existing tests or developing a new test. PMID- 27203276 TI - Prevention of Thumb Web Space Contracture With Multiplanar External Fixation. AB - Thumb web space contracture following hand trauma can be disabling with numerous reconstructive procedures existing to correct the resultant deformity. Following marked soft tissue injury to the hand we utilized the Stryker Hoffmann II Micro External Fixator System to link the first and second metacarpals by a multiplanar system using 1.6 or 2.0 mm self-drilling half-pins and 3 mm carbon fiber connecting rods. This facilitated placement of the thumb in maximal palmar abduction as well as allowed adjustment of thumb position throughout the postoperative period. This technique was performed on 5 patients. Two patients were treated with a first web space external fixator for table saw injuries to the radial aspect of the hand. An additional 2 patients were treated with a first web space external fixator following metacarpophalangeal joint capsular release in the setting of thermal burns. A fifth patient underwent second ray amputation, trapeziectomy and trapezoidectomy for squamous cell carcinoma with subsequent stabilization with the external fixator. The external fixator was left in place until soft tissues were healed (average 5.5 wk). The patients were allowed to mobilize their hand in as much as the external fixator allowed, and no device associated complications were noted. Thumb web space was preserved with passive and supple thumb circumduction and web space abduction/adduction in all patients at an average follow-up of 5 months. The average Quick Dash Score was 35+/-5 and the average Modern Activity Subjective Survey of 2007 was 30+/-8. PMID- 27203275 TI - Sex-Specific Effects of Organophosphate Diazinon on the Gut Microbiome and Its Metabolic Functions. AB - BACKGROUND: There is growing recognition of the significance of the gut microbiome to human health, and the association between a perturbed gut microbiome with human diseases has been established. Previous studies also show the role of environmental toxicants in perturbing the gut microbiome and its metabolic functions. The wide agricultural use of diazinon, an organophosphate insecticide, has raised serious environmental health concerns since it is a potent neurotoxicant. With studies demonstrating the presence of a microbiome-gut brain axis, it is possible that gut microbiome perturbation may also contribute to diazinon toxicity. OBJECTIVES: We investigated the impact of diazinon exposure on the gut microbiome composition and its metabolic functions in C57BL/6 mice. METHODS: We used a combination of 16S rRNA gene sequencing, metagenomics sequencing, and mass spectrometry-based metabolomics profiling in a mouse model to examine the functional impact of diazinon on the gut microbiome. RESULTS: 16S rRNA gene sequencing revealed that diazinon exposure significantly perturbed the gut microbiome, and metagenomic sequencing found that diazinon exposure altered the functional metagenome. Moreover, metabolomics profiling revealed an altered metabolic profile arising from exposure. Of particular significance, these changes were more pronounced for male mice than for female mice. CONCLUSIONS: Diazinon exposure perturbed the gut microbiome community structure, functional metagenome, and associated metabolic profiles in a sex-specific manner. These findings may provide novel insights regarding perturbations of the gut microbiome and its functions as a potential new mechanism contributing to diazinon neurotoxicity and, in particular, its sex-selective effects. Citation: Gao B, Bian X, Mahbub R, Lu K. 2017. Sex-specific effects of organophosphate diazinon on the gut microbiome and its metabolic functions. Environ Health Perspect 125:198 206; http://dx.doi.org/10.1289/EHP202. PMID- 27203277 TI - A Chemical Approach To Break the Planar Configuration of Ag Nanocubes into Tunable Two-Dimensional Metasurfaces. AB - Current plasmonic metasurfaces of nanocubes are limited to planar configurations, restricting the ability to create tailored local electromagnetic fields. Here, we report a new chemical strategy to achieve tunable metasurfaces with nonplanar nanocube orientations, creating novel lattice-dependent field localization patterns. We manipulate the interfacial behaviors of Ag nanocubes by controlling the ratio of hydrophilic/hydrophobic molecules added in a binary thiol mixture during the surface functionalization step. The nanocube orientation at an oil/water interface can consequently be continuously tuned from planar to tilted and standing configurations, leading to the organization of Ag nanocubes into three unique large-area metacrystals, including square close-packed, linear, and hexagonal lattices. In particular, the linear and hexagonal metacrystals are unusual open lattices comprising nonplanar nanocubes, creating unique local electromagnetic field distribution patterns. Large-area "hot hexagons" with significant delocalization of hot spots form in the hexagonal metacrystal. With a lowest packing density of 24%, the hexagonal metacrystal generates nearly 350 fold stronger surface-enhanced Raman scattering as compared to the other denser packing metacrystals, demonstrating the importance of achieving control over the geometrical and spatial orientation of the nanocubes in the metacrystals. PMID- 27203278 TI - Lurasidone: The 2016 update on the pharmacology, efficacy and safety profile. AB - The aim of this paper was to review the up-to-date evidence base on pharmacology and clinical properties of lurasidone. Lurasidone is an atypical antipsychotic, approved by the US Food and Drug Administration (FDA) for the treatment of schizophrenia and bipolar depression. Lurasidone exhibits both an antipsychotic and antidepressant action. Based on its pharmacodynamics profile, it is believed that the drug's clinical action is mediated mainly through the D2, 5-HT2A and 5 HT7 receptors inhibition. In patients with schizophrenia the recommended dose range is 40-80mg/day. In bipolar depression broader dosage ranges (20-120mg/day) were found to be effective. In terms of side effects, higher rates of akathisia, parkinsonism and hyperprolactinemia were observed in individuals receiving lurasidone (as compared to patients treated with other atypical antipsychotics). On the other hand, treatment with lurasidone yields relatively lower risk for developing sedation or overweight/obesity. PMID- 27203279 TI - Which Anesthesia Regimen Is Best to Reduce Morbidity and Mortality in Lung Surgery?: A Multicenter Randomized Controlled Trial. AB - BACKGROUND: One-lung ventilation during thoracic surgery is associated with hypoxia-reoxygenation injury in the deflated and subsequently reventilated lung. Numerous studies have reported volatile anesthesia-induced attenuation of inflammatory responses in such scenarios. If the effect also extends to clinical outcome is yet undetermined. We hypothesized that volatile anesthesia is superior to intravenous anesthesia regarding postoperative complications. METHODS: Five centers in Switzerland participated in the randomized controlled trial. Patients scheduled for lung surgery with one-lung ventilation were randomly assigned to one of two parallel arms to receive either propofol or desflurane as general anesthetic. Patients and surgeons were blinded to group allocation. Time to occurrence of the first major complication according to the Clavien-Dindo score was defined as primary (during hospitalization) or secondary (6-month follow-up) endpoint. Cox regression models were used with adjustment for prestratification variables and age. RESULTS: Of 767 screened patients, 460 were randomized and analyzed (n = 230 for each arm). Demographics, disease and intraoperative characteristics were comparable in both groups. Incidence of major complications during hospitalization was 16.5% in the propofol and 13.0% in the desflurane groups (hazard ratio for desflurane vs. propofol, 0.75; 95% CI, 0.46 to 1.22; P = 0.24). Incidence of major complications within 6 months from surgery was 40.4% in the propofol and 39.6% in the desflurane groups (hazard ratio for desflurane vs. propofol, 0.95; 95% CI, 0.71 to 1.28; P = 0.71). CONCLUSIONS: This is the first multicenter randomized controlled trial addressing the effect of volatile versus intravenous anesthetics on major complications after lung surgery. No difference between the two anesthesia regimens was evident. PMID- 27203283 TI - Disrupting Dimerization Translocates Soluble Epoxide Hydrolase to Peroxisomes. AB - The epoxyeicosatrienoic acid (EET) neutralizing enzyme soluble epoxide hydrolase (sEH) is a neuronal enzyme, which has been localized in both the cytosol and peroxisomes. The molecular basis for its dual localization remains unclear as sEH contains a functional peroxisomal targeting sequence (PTS). Recently, a missense polymorphism was identified in human sEH (R287Q) that enhances its peroxisomal localization. This same polymorphism has also been shown to generate weaker sEH homo-dimers. Taken together, these observations suggest that dimerization may mask the sEH PTS and prevent peroxisome translocation. In the current study, we test the hypothesis that dimerization is a key regulator of sEH subcellular localization. Specifically, we altered the dimerization state of sEH by introducing substitutions in amino acids responsible for the dimer-stabilizing salt-bridge. Green Fluorescent Protein (GFP) fusions of each of mutants were co transfected into mouse primary cultured cortical neurons together with a PTS linked red fluorescent protein to constitutively label peroxisomes. Labeled neurons were analyzed using confocal microscopy and co-localization of sEH with peroxisomes was quantified using Pearson's correlation coefficient. We find that dimer-competent sEH constructs preferentially localize to the cytosol, whereas constructs with weakened or disrupted dimerization were preferentially targeted to peroxisomes. We conclude that the sEH dimerization status is a key regulator of its peroxisomal localization. PMID- 27203284 TI - Behavioral Perceptions of Oakland University Female College Students towards Human Papillomavirus Vaccination. AB - Human Papillomavirus (HPV) vaccination decreases the risk for cervical cancer. However, the uptake of HPV vaccine remains low when compared with other recommended vaccines. This study evaluates the knowledge and attitudes towards HPV infection and vaccination, and the readiness for the uptake of HPV vaccine amongst female students attending Oakland University (OU) in Michigan, United States. This is a cross-sectional study targeting a randomized sample of a 1000 female OU students using an online questionnaire. The data were statistically analyzed using SPSS software. A total of 192 female students, with the mean age of 24 years completed the survey. The majority of participants had previous sexual experience with occasional use of contraceptives (78.1%), were non-smokers (92.7%), and non-alcohol drinkers (54.2%). The participants had a mean knowledge score of 53.0% with a standard error of 2.3% translating to a moderately informed population. The majority agreed that HPV is life threatening (79%), the vaccine prevents cervical cancer (62%), and that side effects would not deter them from vaccination (63%). Although two thirds (67%) believed that, based on sexual practices in the United States, female college students in Michigan have a higher chance of contracting HPV, about 50% did not believe they themselves were at risk. Higher knowledge correlated with increased recommendation for the vaccine (correlation-factor 0.20, p = 0.005). Results suggested that the best predictor for improvement of vaccination was the awareness level and health education. This indicates a need for an educational intervention to raise awareness, increase HPV vaccine uptake, and decrease the incidence of cervical cancer. PMID- 27203285 TI - Fluctuations in Blood Marginal Zone B-Cell Frequencies May Reflect Migratory Patterns Associated with HIV-1 Disease Progression Status. AB - We have previously shown that overexpression of BLyS/BAFF was associated with increased relative frequencies of innate "precursor" marginal zone (MZ)-like B cells in the blood of HIV-1-infected rapid and classic progressors. However, along with relatively normal BLyS/BAFF expression levels, these cells remain unaltered in elite-controllers (EC), rather, percentages of more mature MZ-like B cells are decreased in the blood of these individuals. Fluctuations in frequencies of blood MZ-like B-cell populations may reflect migratory patterns associated with disease progression status, suggesting an important role for these cells in HIV-1 pathogenesis. We have therefore longitudinally measured plasma levels of B-tropic chemokines by ELISA-based technology as well as their ligands by flow-cytometry on blood B-cell populations of HIV-1-infected individuals with different rates of disease progression and uninfected controls. Migration potential of B-cell populations from these individuals were determined by chemotaxis assays. We found important modulations of CXCL13-CXCR5, CXCL12 CXCR4/CXCR7, CCL20-CCR6 and CCL25-CCR9 chemokine-axes and increased cell migration patterns in HIV progressors. Interestingly, frequencies of CCR6 expressing cells were significantly elevated within the precursor MZ-like population, consistent with increased migration in response to CCL20. Although we found little modulation of chemokine-axes in EC, cell migration was greater than that observed for uninfected controls, especially for MZ-like B-cells. Overall the immune response against HIV-1 may involve recruitment of MZ-like B-cells to peripheral sites. Moreover, our findings suggest that "regulated" attraction of these cells in a preserved BLyS/BAFF non-inflammatory environment, such as encountered in EC could be beneficial to the battle and even control of HIV. PMID- 27203286 TI - Easily Accessible Rare-Earth-Containing Phosphonium Room-Temperature Ionic Liquids: EXAFS, Luminescence, and Magnetic Properties. AB - A range of liquid rare earth chlorometallate complexes with the alkyl-phosphonium cation, [P666 14](+), has been synthesized and characterized. EXAFS confirmed the predominant liquid-state speciation of the [LnCl6](3-) ion in the series with Ln = Nd, Eu, Dy. The crystal structure of the shorter-alkyl-chain cation analogue [P4444](+) has been determined and exhibits a very large unit cell. The luminescence properties, with visible-light emissions of the liquid Tb, Eu, Pr, and Sm and the NIR emissions for the Nd and Er compounds, were determined. The effective magnetic moments were measured and fitted for the Nd, Tb, Ho, Dy, Gd, and Er samples. PMID- 27203289 TI - The Author File: Stefan Florian. PMID- 27203287 TI - Normative reference values of thoracic aortic diameter in American College of Radiology Imaging Network (ACRIN 6654) arm of National Lung Screening Trial. AB - PURPOSE: This study aims to establish normative reference values for thoracic aortic diameter (AD) in participants in the National Lung Screening Trial. METHODS: Thoracic AD on 322 prevalence computed tomography was recorded at the sinotubular junction, mid-ascending, transverse arch, mid-descending, and diaphragmatic hiatus. RESULTS: Mean AD (cm) and upper limits of normal for men and women were recorded for at each location. Smoking did not correlate with AD. Age, gender, and body surface area (BSA) were the most significant factors. CONCLUSIONS: Thoracic AD reference values are reported. They do not correlate with smoking, but they did for age, gender, and BSA. PMID- 27203288 TI - The current utility of ultrasound in the diagnosis of acute appendicitis. AB - The purpose of this study is to evaluate the current performance of ultrasound in the diagnosis of acute appendicitis. Retrospectively, patients who presented to a single institution between 2011 and 2012 were included. Diagnostic accuracy was calculated, with surgery considered gold-standard. Our data demonstrates that US relative to surgery-confirmed appendicitis has a sensitivity and specificity of 48.4% and 97.9%, respectively. The diagnostic accuracy was further increased when there was a low pre-test probability, with a NPV of up to 96.6%. Ultrasound has a strong PPV in the diagnosis of acute appendicitis, and in equivocal cases, the NPV is reliable. PMID- 27203290 TI - Optimization of a model of out-of-hospital antibiotic therapy (OPAT) in a Belgian university hospital resulting in a proposal for national implementation. AB - OBJECTIVES: Some infections require prolonged parenteral antimicrobial therapy, which can be continued in an outpatient setting. The Ghent University Hospital has 15 years of experience with Outpatient Parenteral Antimicrobial Therapy (OPAT) in the home setting of the patient. METHODS: Multidisciplinary critical approach through identification of areas for improvement with the existing OPAT process within the Ghent University Hospital. Existing literature and guidelines were used as references. An improved model is proposed for implementation. RESULTS: Several challenges and barriers were identified, including regulatory obstacles for OPAT in Belgium, such as lack of uniformity in ambulatory reimbursement of parenteral antimicrobials. There is no financial incentive for the patient with OPAT, as costs for the patient of outpatient therapy can be higher as compared with hospitalization. Other barriers include delayed approval of the certificate for reimbursement, low availability of medicines in the community pharmacies and limited knowledge of the medical devices for administration in ambulatory setting. All critical steps in the revised OPAT program are summarized in a flowchart with a checklist for all stakeholders. Firstly, a list with specific criteria to include patients in an OPAT program is provided. Secondly, the Multidisciplinary Infection Team received a formal mandate to review all eligible OPAT patients. In order to select the most appropriate catheter, a decision tree was developed and standardized packages with medical devices were developed. Thirdly, patients receive oral and written information about the treatment with practical and financial implications. Fourthly, information is provided toward the general practitioners, community pharmacist and home care nurse. CONCLUSION: Standardization of the OPAT program aims at improving quality and safety of intravenous antimicrobial therapy in the home setting. PMID- 27203291 TI - Pepluane and Paraliane Diterpenoids from Euphorbia peplus with Potential Anti inflammatory Activity. AB - Twelve new diterpenoids based on two rare skeletal types, namely, paralianones A D (1-4) and pepluanols A-H (5-12), along with five known compounds, were isolated from an acetone extract of Euphorbia peplus. Their structures were proposed based on 1D and 2D NMR spectroscopic data analysis. These diterpenoids were evaluated for potential anti-inflammatory activity in a lipopolysaccharide-stimulated mouse macrophage cellular model. Compounds 3, 4, 11, 13, and 16 displayed moderate inhibitory effects on NO inhibition, with IC50 values ranging from 29.9 to 38.3 MUM. PMID- 27203292 TI - Isotopic Evidence for Reductive Immobilization of Uranium Across a Roll-Front Mineral Deposit. AB - We use uranium (U) isotope ratios to detect and quantify the extent of natural U reduction in groundwater across a roll front redox gradient. Our study was conducted at the Smith Ranch-Highland in situ recovery (ISR) U mine in eastern Wyoming, USA, where economic U deposits occur in the Paleocene Fort Union formation. To evaluate the fate of aqueous U in and adjacent to the ore body, we investigated the chemical composition and isotope ratios of groundwater samples from the roll-front type ore body and surrounding monitoring wells of a previously mined area. The (238)U/(235)U of groundwater varies by approximately 30/00 and is correlated with U concentrations. Fluid samples down-gradient of the ore zone are the most depleted in (238)U and have the lowest U concentrations. Activity ratios of (234)U/(238)U are ~5.5 up-gradient of the ore zone, ~1.0 in the ore zone, and between 2.3 and 3.7 in the down-gradient monitoring wells. High precision measurements of (234)U/(238)U and (238)U/(235)U allow for development of a conceptual model that evaluates both the migration of U from the ore body and the extent of natural attenuation due to reduction. We find that the premining migration of U down-gradient of the delineated ore body is minimal along eight transects due to reduction in or adjacent to the ore body, whereas two other transects show little or no sign of reduction in the down-gradient region. These results suggest that characterization of U isotopic ratios at the mine planning stage, in conjunction with routine geochemical analyses, can be used to identify where more or less postmining remediation will be necessary. PMID- 27203295 TI - Estimation of the composition of intermetallic compounds in LiCl-KCl molten salt by cyclic voltammetry. AB - In this work, the compositions of Ce-Al, Er-Al and La-Bi intermetallic compounds were estimated by the cyclic voltammetry (CV) technique. At first, CV measurements were carried out at different reverse potentials to study the co reduction processes of Ce-Al, Er-Al and La-Bi systems. The CV curves obtained were then re-plotted with the current as a function of time, and the coulomb number of each peak was calculated. By comparing the coulomb number of the related peaks, the compositions of the Ce-Al, Er-Al and La-Bi intermetallic compounds formed in the co-reduction process could be estimated. The results showed that Al11Ce3, Al3Ce, Al2Ce and AlCe could be formed by the co-reduction of Ce(iii) and Al(iii). For the co-reduction of Er(iii) and Al(iii), Al3Er2, Al2Er and AlEr were formed. In a La(iii) and Bi(iii) co-existing system in LiCl-KCl melts, LaBi2, LaBi and Li3Bi were the major products as a result of co-reduction. PMID- 27203293 TI - Implementing Metal-to-Ligand Charge Transfer in Organic Semiconductor for Improved Visible-Near-Infrared Photocatalysis. AB - The coordination of organic semiconductors with metal cations can induce metal-to ligand charge transfer, which broadens light absorption to cover the visible-near infrared (vis-NIR) spectrum. As a proof-of-concept demonstration, the g-C3 N4 based complex exhibits dramatically enhanced photocatalytic H2 production with excellent durability under vis-NIR irradiation. PMID- 27203294 TI - The early component of middle latency auditory-evoked potentials in the process of deviance detection. AB - The aim of the present study was to investigate both the encoding mechanism and the process of deviance detection when deviant stimuli were presented in various patterns in an environment featuring repetitive sounds. In adults with normal hearing, middle latency responses were recorded within an oddball paradigm containing complex tones or speech sounds, wherein deviant stimuli featured different change patterns. For both complex tones and speech sounds, the Na and Pa components of middle latency responses showed an increase in the mean amplitude and a reduction in latency when comparing rare deviant stimuli with repetitive standard stimuli in a stimulation block. However, deviant stimuli with a rising frequency induced signals with smaller amplitudes than other deviant stimuli. The present findings indicate that deviant stimuli with different change patterns induce differing responses in the primary auditory cortex. In addition, the Pa components of speech sounds typically feature a longer latency and similar mean amplitude compared with complex tones, which suggests that the auditory system requires more complex processing for the analysis of speech sounds before processing in the auditory cortex. PMID- 27203296 TI - Comment on 'The influence of antioxidant THPC on the properties of polymer gel dosimeter'. PMID- 27203297 TI - Often times, we should look at IVF more simply. PMID- 27203298 TI - Elective single embryo transfer: Is frozen better than fresh? AB - OBJECTIVE: Single embryo transfer (SET) has been recommended to avoid multiple births following assisted reproductive technology (ART) procedures. Many studies have shown that frozen embryo transfer may yield better pregnancy rates than fresh embryo transfer. This study looked into pregnancy rates following fresh versus frozen single embryo transfer procedures in age-matched patients. METHODS: This retrospective case control study was carried out at a private clinic [NewLife Fertility Clinic, ON, Canada]. Patient groups included infertile women treated with IVF/ICSI and elective single embryo transfer (eSET) given either fresh or frozen embryos. Cycle outcomes were compared between patient groups matched by age. The primary endpoints were positive testing for beta-hCG and viable ongoing pregnancy. The secondary endpoints were live birth and miscarriage rates. RESULTS: A total of 583 eSET cycles (212 fresh transfer cycles and 371 frozen transfer cycles) were performed. Significantly higher pregnancy and live birth rates were observed among patients aged <= 39 years given frozen embryos. CONCLUSION: Frozen single embryo transfer was associated with higher pregnancy and live birth rates when compared to fresh single embryo transfer. PMID- 27203299 TI - Strategies for the management of OHSS: Results from freezing-all cycles. AB - OBJECTIVE: To compare the use of GnRH agonist (GnRHa) or hCG trigger in potential OHSS patients undergoing freeze-all programs. We also compared the clinical outcomes when fresh versus freeze-thawed embryo transfers were performed in cycles with a high number of retrieved oocytes. METHODS: The study included potential OHSS patients who received GnRHa (n=74) or hCG (n=49) trigger. The protocols were compared with respect to the clinical outcomes. We also compared the clinical outcomes of cycles in which hCG trigger was used and more than 20 MII oocytes were retrieved when: fresh embryo transfer protocol (n=153) or freeze all protocol (n=123) were performed. RESULTS: A decreased serum estradiol level, a decreased number of retrieved oocytes, an increased MII retrieved rate, and decreased fertilization rate was observed in the hCG when compared with the GnRHa group. No significant differences were noted concerning clinical outcomes. When fresh cycles were compared with frozen-thawed cycles, the estradiol serum level and the number of cryopreserved embryos were higher in the frozen-thawed cycles. The clinical pregnancy rate was higher among freeze-all cycles, as well as the implantation and cumulative pregnancy rates, when compared with fresh embryo transfer cycles. CONCLUSION: The use of GnRHa trigger may be a good alternative to prevent the OHSS in patients presenting an extreme ovarian response to COS, leading to similar clinical outcomes, when compared with the traditional hCG trigger. Moreover, our findings demonstrated that the strategy of freezing-all embryos not only decreases the risk of OHSS but also leads to a better pregnancy rate. PMID- 27203300 TI - Low progesterone levels and ovulation by ultrasound assessment in infertile patients. AB - OBJECTIVE: To assess the correlation between low levels of progesterone and ovulation by ultrasound monitoring in infertile patients with regular menstrual cycles. METHODS: Case-control study. The sample consisted of 302 women aged 20-40 years, treated from 2000 to 2014 in the Human Reproduction Laboratory of the University Hospital of the Federal University of Goias and in the Department of Gynecology and Obstetrics in Goiania, Goias. Data collection was performed by analysis of physical records (Medical Records and Health Information Services) and electronic ones (Sisfert(c), 2004) after approval by a Human Research Ethics Committee. Patients were classified according to their ovulatory status, evaluated by progesterone levels and ultrasound monitoring and divided into two groups: Group I (anovulatory cycle patients, n=74) and Group II (ovulatory patients, n=228). In both groups associations were made between the percentage of patients with normal progesterone (>= 10 ng/ml) and percentage of patients with low progesterone (5.65 - 9.9 ng/ml). The groups were paired for comparisons related to age, body mass index, duration of infertility, follicle stimulating hormone (FSH), thyroid stimulating hormone (TSH), luteinizing hormone (LH) and estradiol (E2). RESULTS: There was a significant association between the percentage of ovulation by ultrasound monitoring and the percentages of patients who presented low levels of progesterone. CONCLUSION: The study suggests that low serum levels of progesterone are associated with low percentage of ovulation in infertile women with regular menstrual cycles and women with unexplained infertility. PMID- 27203301 TI - Assessment of sperm DNA in patients submitted the assisted reproduction technology procedures. AB - OBJECTIVE: This study aimed to produce data on sperm quality while maintaining the integrity of sperm DNA samples taken from patients submitted to in vitro fertilization (IVF) procedures at our center, and determine whether increased levels of histones were associated with sperm DNA damage and decreased fertilization, cleavage, and pregnancy rates. Such findings might shed light on the physiology and outcomes of pregnancy. METHODS: Semen samples from 27 patients divided into two groups were analyzed. The case group included individuals offered IVF; the control group had subjects with normal spermograms. Sperm DNA structure was assessed through phosphorylated histone H2AX analysis by flow cytometry. RESULTS: The patients with altered sperm parameters had more histones in sperm chromatin than the individuals with normal sperm parameters. CONCLUSION: Results indicated that increased levels of histone in sperm chromatin do not affect embryo production, but affect the cleavage rate, embryo quality, and might thus reduce pregnancy rates. The integrity of the paternal genome is of paramount importance in the initiation and maintenance of a viable pregnancy in patients treated with assisted reproduction technology procedures. Further studies on sperm diagnostic tests at a nuclear level might improve the treatment offered to infertile couples. PMID- 27203302 TI - A prospective randomized study comparing two commercially available types of human embryo culture media: G1-PLUSTM/G2-PLUSTM sequential medium (Vitrolife) and the GL BLASTTM sole medium (Ingamed). AB - OBJECTIVE: To check the efficacy of two types of commercially available embryo culture medium: G1-PLUSTM/G2-PLUSTM sequential (Vitrolife, Gothenburg, Sweden) and GV BLASTTM sole (Ingamed, Maringa, Brazil) with regards to fertilization, cleavage, blastocyst and pregnancy rates. METHODS: Prospective and randomized study conducted from March to July 2015, using the medical records of 60 patients submitted to Intracytoplasmic Sperm Injection techniques (ICSI). Data regarding the age of patients, together with fertilization, cleavage, blastocyst and pregnancy rates, were collected and compared in relation to the: G1-PLUSTM/G2 PLUSTM sequential and GV BLASTTM sole mediums. The data were tabulated and compared using the Pearson's Chi-Square test (95% CI). RESULTS: There was no significant difference when comparing patients divided into higher and lower fertility age. No significant statistical difference was noted between the fertilization rates (P=0.59), cleavage (P=0.91), evolution to blastocyst (P=0.33) and total pregnancy (P=0.83) when comparing the embryos cultured in the different media analysed. CONCLUSION: We conclude that the G1-PLUSTM/G2-PLUSTM sequential and GV BLASTTM sole mediums are equally effective with regards to fertilization, cleavage, blastocyst development and total pregnancy rates. PMID- 27203303 TI - The impact of age on blastocyst scoring after single and double embryo transfers. AB - OBJECTIVE: The aim of the present study was to assess the putative relationship between patient's age and blastocyst scores, in single (SET) or double (DET) transfer cycles, that resulted in single or twin pregnancy or non-pregnancy. Second, we analyzed the effect of maternal age on clinical gestation and implantation rates after single and double blastocyst transfers. METHODS: Retrospective analysis of 164 assisted reproduction cycles with embryo transfers. RESULTS: Data demonstrated that for both, young (<35 years of age) and older (>=35 years of age) women, trophectoderm (TE) score is the most important parameter to assess concerning embryo selection. However, inner cell mass (ICM) also plays an important role on blastocyst selection in the group of older patients. In addition, our data shows that for young women the transfer of a single blastocyst results in similar gestational rates as those for DET. CONCLUSION: We suggest that blastocyst grading for patients aged 35 years or above shall be performed using a strict grading policy, possibly not of a single parameter, but TE, ICM and expansion grades together, to choose the "best combined-score blastocyst". DETs should be considered, particularly after previous cycles with pregnancy failures. PMID- 27203304 TI - Stem cells and uterine leiomyomas: What is the evidence? AB - Uterine leiomyomas, also known as uterine fibroids or uterine myomas, are the most common benign gynecologic tumors found in women of reproductive age. In spite of the numerous published studies evaluating the hormonal dependency, epidemiology, molecular biology, pathology, and genetics of leiomyomas, many questions remain unanswered. The remodeling of the uterus in response to hormonal stimuli and its return to a basal state may be related to adult stem/progenitor cells residing in the endometrial and myometrial layers. Recent published papers on stem cells and their paracrine interactions with more specialized cell populations within leiomyomas may help establish the missing link between the development of treatments designed to stop the growth of leiomyomas and therapies devised to eliminate them. Therefore, this study aimed to address the current paradigm regarding the evidence available on the role of stem/progenitor cells in the pathogenesis of uterine leiomyoma. Only a handful of studies involving humans have been published to date describing the presence of somatic stem cells (SSCs) in the myometrium and leiomyomas. No solid conclusion has been established thus far. Despite the fact that these studies strongly pointed to the vital role human leiomyoma stem cells might play in initiating the development of myomas, huge gaps still persist in the literature. Studies to identify putative myometrial and leiomyoma-specific markers might offer new possibilities for understanding the origin of these tumors and perhaps help develop new nonsurgical noninvasive treatments. PMID- 27203305 TI - Human follicular fluid and effects on reproduction. AB - Fertility - the ability to produce offspring - is considered a prerequisite for the development and perpetuation of species. Several factors may positively or negatively affect one's reproductive capabilities, such as regular exercises and maintaining a healthy bodyweight, versus aging, obesity, and stress. Follicular fluid (FF) is a liquid composed primarily of hormones, enzymes, anticoagulants, electrolytes, reactive oxygen species and antioxidants, which fills the follicular antrum and acts as an important mediator in the communication between cells in the antral follicle while bathing and carrying nutrients to the oocyte. Thus, human FF is a key element to the success of natural fertilization present in every stage of the conception process, from the communication between gametes to the development of fully viable embryos, and a vital component in the occurrence of spontaneous pregnancies. This literature review aimed to describe the possible effects of human follicular fluid on the natural fertilization process and to assess its role in follicular growth, oocyte quality, sperm capacitation, fertilization, and early embryonic development. PMID- 27203306 TI - Is mesenteric lymphadenitis a cause of ovarian reserve reduction? - Case Report. AB - Mesenteric lymphadenitis is a clinical condition that affects mostly children and teenagers. Its symptoms include fever, severe abdominal pain, nausea, and, in some cases, diarrhea, constipation, and acute abdomen. This paper describes the case of a 16-year-old patient with mesenteric lymphadenitis submitted to an exploratory laparoscopy for suppurative lymph nodes that evolved to a drastic reduction of ovarian reserve. Because of the patients age, she was offered cryopreservation of her ovarian tissue. PMID- 27203307 TI - A successful healthy live birth from a female patient with hypogonadotropic hypogonadism and oocytes with unusually large cytoplasmic inclusions. AB - This study aimed to report the case of a successful live birth from a woman having oocytes with abnormally large cytoplasmic inclusions. The patient described in this case is a 28 year-old woman with hypogonadotropic hypogonadism (HH) with a history of two previous unsuccessful in vitro fertilization (IVF) attempts offered an antagonist protocol. Stimulation was performed with human menopausal gonadotropin 300 IU/day. The intracytoplasmic sperm injection (ICSI) procedure was performed 4-6 hours after oocyte aspiration for all mature oocytes. Six oocytes were retrieved, five of which mature (MII). All oocytes had abnormal cytoplasmic structures. Two were fertilized after ICSI and two top quality embryos were transferred on Day 2. Our case report suggests that HH patients with refractile bodies/lipofuscin in their oocytes may not have their pregnancies negatively affected. While there have been several reports of successful births from dysmorphic oocytes, no cases of successful pregnancies followed by live births from young women with HH and oocytes with large cytoplasmic inclusions had been reported to date. PMID- 27203308 TI - Corrigendum: Spinal cord injury affects the interplay between visual and sensorimotor representations of the body. PMID- 27203309 TI - Experiment Investigating the Connection between Weak Values and Contextuality. AB - Weak value measurements have recently given rise to a great amount of interest in both the possibility of measurement amplification and the chance for further quantum mechanics foundations investigation. In particular, a question emerged about weak values being proof of the incompatibility between quantum mechanics and noncontextual hidden variables theories (NCHVTs). A test to provide a conclusive answer to this question was given by Pusey [Phys. Rev. Lett. 113, 200401 (2014)], where a theorem was derived showing the NCHVT incompatibility with the observation of anomalous weak values under specific conditions. In this Letter we realize this proposal, clearly pointing out the connection between weak values and the contextual nature of quantum mechanics. PMID- 27203310 TI - Fisher-Symmetric Informationally Complete Measurements for Pure States. AB - We introduce a new kind of quantum measurement that is defined to be symmetric in the sense of uniform Fisher information across a set of parameters that uniquely represent pure quantum states in the neighborhood of a fiducial pure state. The measurement is locally informationally complete-i.e., it uniquely determines these parameters, as opposed to distinguishing two arbitrary quantum states-and it is maximal in the sense of a multiparameter quantum Cramer-Rao bound. For a d dimensional quantum system, requiring only local informational completeness allows us to reduce the number of outcomes of the measurement from a minimum close to but below 4d-3, for the usual notion of global pure-state informational completeness, to 2d-1. PMID- 27203311 TI - High-Fidelity Resonator-Induced Phase Gate with Single-Mode Squeezing. AB - We propose to increase the fidelity of two-qubit resonator-induced phase gates in circuit QED by the use of narrow-band single-mode squeezing. We show that there exists an optimal squeezing angle and strength that erases qubit "which-path" information leaking out of the cavity and thereby minimizes qubit dephasing during these gates. Our analytical results for the gate fidelity are in excellent agreement with numerical simulations of a cascaded master equation that takes into account the dynamics of the source of squeezed radiation. With realistic parameters, we find that it is possible to realize a controlled-phase gate with a gate time of 200 ns and average infidelity of 10^{-5}. PMID- 27203312 TI - Effects of Neutron-Star Dynamic Tides on Gravitational Waveforms within the Effective-One-Body Approach. AB - Extracting the unique information on ultradense nuclear matter from the gravitational waves emitted by merging neutron-star binaries requires robust theoretical models of the signal. We develop a novel effective-one-body waveform model that includes, for the first time, dynamic (instead of only adiabatic) tides of the neutron star as well as the merger signal for neutron-star-black hole binaries. We demonstrate the importance of the dynamic tides by comparing our model against new numerical-relativity simulations of nonspinning neutron star-black-hole binaries spanning more than 24 gravitational-wave cycles, and to other existing numerical simulations for double neutron-star systems. Furthermore, we derive an effective description that makes explicit the dependence of matter effects on two key parameters: tidal deformability and fundamental oscillation frequency. PMID- 27203313 TI - Exact Mass-Coupling Relation for the Homogeneous Sine-Gordon Model. AB - We derive the exact mass-coupling relation of the simplest multiscale quantum integrable model, i.e., the homogeneous sine-Gordon model with two mass scales. The relation is obtained by comparing the perturbed conformal field theory description of the model valid at short distances to the large distance bootstrap description based on the model's integrability. In particular, we find a differential equation for the relation by constructing conserved tensor currents, which satisfy a generalization of the Theta sum rule Ward identity. The mass coupling relation is written in terms of hypergeometric functions. PMID- 27203314 TI - Higher Spin Interactions from Conformal Field Theory: The Complete Cubic Couplings. AB - In this Letter we provide a complete holographic reconstruction of the cubic couplings in the minimal bosonic higher spin theory in (d+1)-dimensional anti- de Sitter space. For this purpose, we also determine the operator-product expansion coefficients of all single-trace conserved currents in the d-dimensional free scalar O(N) vector model, and we compute the tree-level three-point Witten diagram amplitudes for a generic cubic interaction of higher spin gauge fields in the metriclike formulation. PMID- 27203316 TI - First Evidence of Shape Coexistence in the ^{78}Ni Region: Intruder 0_{2}^{+} State in ^{80}Ge. AB - The N=48 ^{80}Ge nucleus is studied by means of beta-delayed electron-conversion spectroscopy at ALTO. The radioactive ^{80}Ga beam is produced through the isotope separation on line photofission technique and collected on a movable tape for the measurement of gamma and e^{-} emission following beta decay. An electric monopole E0 transition, which points to a 639(1) keV intruder 0_{2}^{+} state, is observed for the first time. This new state is lower than the 2_{1}^{+} level in ^{80}Ge, and provides evidence of shape coexistence close to one of the most neutron-rich doubly magic nuclei discovered so far, ^{78}Ni. This result is compared with theoretical estimates, helping to explain the role of monopole and quadrupole forces in the weakening of the N=50 gap at Z=32. The evolution of intruder 0_{2}^{+} states towards ^{78}Ni is discussed. PMID- 27203318 TI - Adiabatic Field-Free Alignment of Asymmetric Top Molecules with an Optical Centrifuge. AB - We use an optical centrifuge to align asymmetric top SO_{2} molecules by adiabatically spinning their most polarizable O-O axis. The effective centrifugal potential in the rotating frame confines the sulfur atoms to the plane of the laser-induced rotation, leading to the planar molecular alignment that persists after the molecules are released from the centrifuge. The periodic appearance of the full three-dimensional alignment, typically observed only with linear and symmetric top molecules, is also detected. Together with strong in-plane centrifugal forces, which bend the molecules by up to 10 deg, permanent field free alignment offers new ways of controlling molecules with laser light. PMID- 27203317 TI - Isomer Shift and Magnetic Moment of the Long-Lived 1/2^{+} Isomer in _{30}^{79}Zn_{49}: Signature of Shape Coexistence near ^{78}Ni. AB - Collinear laser spectroscopy is performed on the _{30}^{79}Zn_{49} isotope at ISOLDE-CERN. The existence of a long-lived isomer with a few hundred milliseconds half-life is confirmed, and the nuclear spins and moments of the ground and isomeric states in ^{79}Zn as well as the isomer shift are measured. From the observed hyperfine structures, spins I=9/2 and I=1/2 are firmly assigned to the ground and isomeric states. The magnetic moment MU (^{79}Zn)=-1.1866(10)MU_{N}, confirms the spin-parity 9/2^{+} with a nug_{9/2}^{-1} shell-model configuration, in excellent agreement with the prediction from large scale shell-model theories. The magnetic moment MU (^{79m}Zn)=-1.0180(12)MU_{N} supports a positive parity for the isomer, with a wave function dominated by a 2h-1p neutron excitation across the N=50 shell gap. The large isomer shift reveals an increase of the intruder isomer mean square charge radius with respect to that of the ground state, delta?r_{c}^{2}?^{79,79m}=+0.204(6) fm^{2}, providing first evidence of shape coexistence. PMID- 27203319 TI - Visibility of Young's Interference Fringes: Scattered Light from Small Ion Crystals. AB - We observe interference in the light scattered from trapped ^{40}Ca^{+} ion crystals. By varying the intensity of the excitation laser, we study the influence of elastic and inelastic scattering on the visibility of the fringe pattern and discriminate its effect from that of the ion temperature and wave packet localization. In this way we determine the complex degree of coherence and the mutual coherence of light fields produced by individual atoms. We obtain interference fringes from crystals consisting of two, three, and four ions in a harmonic trap. Control of the trapping potential allows for the adjustment of the interatomic distances and thus the formation of linear arrays of atoms serving as a regular grating of microscopic scatterers. PMID- 27203320 TI - Continuous Cold-Atom Inertial Sensor with 1 nrad/sec Rotation Stability. AB - We report the operation of a cold-atom inertial sensor which continuously captures the rotation signal. Using a joint interrogation scheme, where we simultaneously prepare a cold-atom source and operate an atom interferometer (AI), enables us to eliminate the dead times. We show that such continuous operation improves the short-term sensitivity of AIs, and demonstrate a rotation sensitivity of 100 nrad/sec/sqrt[Hz] in a cold-atom gyroscope of 11 cm^{2} Sagnac area. We also demonstrate a rotation stability of 1 nrad/sec at 10^{4} sec of integration time, which represents the state of the art for atomic gyroscopes. The continuous operation of cold-atom inertial sensors will lead to large area AIs at their full sensitivity potential, determined by the quantum noise limit. PMID- 27203321 TI - Optical Resonance Shifts in the Fluorescence of Thermal and Cold Atomic Gases. AB - We show that the resonance shifts in the fluorescence of a cold gas of rubidium atoms substantially differ from those of thermal atomic ensembles that obey the standard continuous medium electrodynamics. The analysis is based on large-scale microscopic numerical simulations and experimental measurements of the resonance shifts in a steady-state response in light propagation. PMID- 27203322 TI - Ultrafast Optimal Sideband Cooling under Non-Markovian Evolution. AB - A sideband cooling strategy that incorporates (i) the dynamics induced by structured (non-Markovian) environments in the target and auxiliary systems and (ii) the optimally time-modulated interaction between them is developed. For the context of cavity optomechanics, when non-Markovian dynamics are considered in the target system, ground state cooling is reached at much faster rates and at a much lower phonon occupation number than previously reported. In contrast to similar current strategies, ground state cooling is reached here for coupling strength rates that are experimentally accessible for the state-of-the-art implementations. After the ultrafast optimal-ground-state-cooling protocol is accomplished, an additional optimal control strategy is considered to maintain the phonon number as close as possible to the one obtained in the cooling procedure. Contrary to the conventional expectation, when non-Markovian dynamics are considered in the auxiliary system, the efficiency of the cooling protocol is undermined. PMID- 27203323 TI - Observation of Geometric Parametric Instability Induced by the Periodic Spatial Self-Imaging of Multimode Waves. AB - Spatiotemporal mode coupling in highly multimode physical systems permits new routes for exploring complex instabilities and forming coherent wave structures. We present here the first experimental demonstration of multiple geometric parametric instability sidebands, generated in the frequency domain through resonant space-time coupling, owing to the natural periodic spatial self-imaging of a multimode quasi-continuous-wave beam in a standard graded-index multimode fiber. The input beam was launched in the fiber by means of an amplified microchip laser emitting sub-ns pulses at 1064 nm. The experimentally observed frequency spacing among sidebands agrees well with analytical predictions and numerical simulations. The first-order peaks are located at the considerably large detuning of 123.5 THz from the pump. These results open the remarkable possibility to convert a near-infrared laser directly into a broad spectral range spanning visible and infrared wavelengths, by means of a single resonant parametric nonlinear effect occurring in the normal dispersion regime. As further evidence of our strong space-time coupling regime, we observed the striking effect that all of the different sideband peaks were carried by a well-defined and stable bell-shaped spatial profile. PMID- 27203324 TI - Conical Diffraction and Composite Lieb Bosons in Photonic Lattices. AB - Pseudospin describes how waves are distributed between different "internal" degrees of freedom or microscopic states, such as polarizations, sublattices, or layers. Here, we experimentally demonstrate and explain wave dynamics in a photonic Lieb lattice, which hosts an integer pseudospin s=1 conical intersection. We study the most striking differences displayed by integer pseudospin states: pseudospin-dependent conical diffraction and the generation of higher charged optical vortices. PMID- 27203325 TI - Chladni Patterns in a Liquid at Microscale. AB - By means of ultrathin silicon membranes excited in the low ultrasound range, we show for the first time that it is possible to form two-dimensional Chladni patterns of microbeads in liquid. Unlike the well-known effect in a gaseous environment at the macroscale, where gravity effects are generally dominant, leading particles towards the nodal regions of displacement, we show that the combined effects of an ultrathin plate excited at low frequency (yielding to subsonic waves) together with reduced gravity (arising from buoyancy) will enhance the importance of microstreaming in the Chladni problem. Here, we report that for micrometric beads larger than the inner streaming layer, the microscale streaming in the vicinity of the plate tends to gather particles in antinodal regions of vibrations yielding to patterns in good agreement with the predicted modes for a liquid-loaded plate. Interestingly, a symmetry breaking phenomenon together with the streaming can trigger movements of beads departing from one cluster to another. We show that, for higher modes, this movement can appear as a collective rotation of the beads in the manner of a "farandole." PMID- 27203326 TI - Defects at the Nanoscale Impact Contact Line Motion at all Scales. AB - The contact angle of a liquid drop moving on a real solid surface depends on the speed and direction of motion of the three-phase contact line. Many experiments have demonstrated that pinning on surface defects, thermal activation and viscous dissipation impact contact line dynamics, but so far, efforts have failed to disentangle the role of each of these dissipation channels. Here, we propose a unifying multiscale approach that provides a single quantitative framework. We use this approach to successfully account for the dynamics measured in a classic dip-coating experiment performed over an unprecedentedly wide range of velocity. We show that the full contact line dynamics up to the liquid film entrainment threshold can be parametrized by the size, amplitude and density of nanometer scale defects. This leads us to reinterpret the contact angle hysteresis as a dynamical crossover rather than a depinning transition. PMID- 27203328 TI - Anticorrelated Emission of High Harmonics and Fast Electron Beams From Plasma Mirrors. AB - We report for the first time on the anticorrelated emission of high-order harmonics and energetic electron beams from a solid-density plasma with a sharp vacuum interface-plasma mirror-driven by an intense ultrashort laser pulse. We highlight the key role played by the nanoscale structure of the plasma surface during the interaction by measuring the spatial and spectral properties of harmonics and electron beams emitted by a plasma mirror. We show that the nanoscale behavior of the plasma mirror can be controlled by tuning the scale length of the electron density gradient, which is measured in situ using spatial domain interferometry. PMID- 27203327 TI - Tunable High-Intensity Electron Bunch Train Production Based on Nonlinear Longitudinal Space Charge Oscillation. AB - High-intensity trains of electron bunches with tunable picosecond spacing are produced and measured experimentally with the goal of generating terahertz (THz) radiation. By imposing an initial density modulation on a relativistic electron beam and controlling the charge density over the beam propagation, density spikes of several-hundred-ampere peak current in the temporal profile, which are several times higher than the initial amplitudes, have been observed for the first time. We also demonstrate that the periodic spacing of the bunch train can be varied continuously either by tuning launching phase of a radio-frequency gun or by tuning the compression of a downstream magnetic chicane. Narrow-band coherent THz radiation from the bunch train was also measured with MUJ-level energies and tunable central frequency of the spectrum in the range of ~0.5 to 1.6 THz. Our results pave the way towards generating mJ-level narrow-band coherent THz radiation and driving high-gradient wakefield-based acceleration. PMID- 27203329 TI - Internal Transport Barrier Broadening through Subdominant Mode Stabilization in Reversed Field Pinch Plasmas. AB - The reversed field pinch (RFP) device RFX-mod features strong internal transport barriers when the plasma accesses states with a single dominant helicity. Such transport barriers enclose a hot helical region with high confinement whose amplitude may vary from a tiny one to an amplitude encompassing an appreciable fraction of the available volume. The transition from narrow to wide thermal structures has been ascribed so far to the transport reduction that occurs when the dominant mode separatrix, which is a preferred location for the onset of stochastic field lines, disappears. In this Letter we show instead that the contribution from the separatrix disappearance, by itself, is marginal and the main role is instead played by the progressive stabilization of secondary modes. The position and the width of the stochastic boundary encompassing the thermal structures have been estimated by applying the concept of a 3D quasiseparatrix layer, developed in solar physics to treat reconnection phenomena without true separatrices and novel to toroidal laboratory plasmas. Considering the favorable scaling of secondary modes with the Lundquist number, these results open promising scenarios for RFP plasmas at temperatures higher than the presently achieved ones, where lower secondary modes and, consequently, larger thermal structures are expected. Furthermore, this first application of the quasiseparatrix layer to a toroidal plasma indicates that such a concept is ubiquitous in magnetic reconnection, independent of the system geometry under investigation. PMID- 27203330 TI - Enhanced Multi-MeV Photon Emission by a Laser-Driven Electron Beam in a Self Generated Magnetic Field. AB - We use numerical simulations to demonstrate that a source of collimated multi-MeV photons with high conversion efficiency can be achieved using an all-optical single beam setup at an intensity of 5*10^{22} W/cm^{2} that is already within reach of existing laser facilities. In the studied setup, an unprecedented quasistatic magnetic field (0.4 MT) is driven in a significantly overdense plasma, coupling three key aspects of laser-plasma interactions at high intensities: relativistic transparency, direct laser acceleration, and synchrotron photon emission. The quasistatic magnetic field enhances the photon emission process, which has a profound impact on electron dynamics via radiation reaction and yields tens of TW of directed MeV photons for a PW-class laser. PMID- 27203331 TI - Collisional Dynamics of Half-Quantum Vortices in a Spinor Bose-Einstein Condensate. AB - We present an experimental study on the interaction and dynamics of half-quantum vortices (HQVs) in an antiferromagnetic spinor Bose-Einstein condensate. By exploiting the orbit motion of a vortex dipole in a trapped condensate, we perform a collision experiment of two HQV pairs, and observe that the scattering motions of the HQVs is consistent with the short-range vortex interaction that arises from nonsingular magnetized vortex cores. We also investigate the relaxation dynamics of turbulent condensates containing many HQVs, and demonstrate that spin wave excitations are generated by the collisional motions of the HQVs. The short-range vortex interaction and the HQV-magnon coupling represent two characteristics of the HQV dynamics in the spinor superfluid. PMID- 27203315 TI - Measurement of Muon Antineutrino Oscillations with an Accelerator-Produced Off Axis Beam. AB - T2K reports its first measurements of the parameters governing the disappearance of nu[over -]_{MU} in an off-axis beam due to flavor change induced by neutrino oscillations. The quasimonochromatic nu[over -]_{MU} beam, produced with a peak energy of 0.6 GeV at J-PARC, is observed at the far detector Super-Kamiokande, 295 km away, where the nu[over -]_{MU} survival probability is expected to be minimal. Using a data set corresponding to 4.01*10^{20} protons on target, 34 fully contained MU-like events were observed. The best-fit oscillation parameters are sin^{2}(theta[over -]_{23})=0.45 and |Deltam[over -]_{32}^{2}|=2.51*10^{-3} eV^{2} with 68% confidence intervals of 0.38-0.64 and 2.26-2.80*10^{-3} eV^{2}, respectively. These results are in agreement with existing antineutrino parameter measurements and also with the nu_{MU} disappearance parameters measured by T2K. PMID- 27203332 TI - Lattice Dynamics of EuO: Evidence for Giant Spin-Phonon Coupling. AB - Comprehensive studies of lattice dynamics in the ferromagnetic semiconductor EuO have been performed by a combination of inelastic x-ray scattering, nuclear inelastic scattering, and ab initio calculations. A remarkably large broadening of the transverse acoustic phonons was discovered at temperatures above and below the Curie temperature T_{C}=69 K. This result indicates a surprisingly strong momentum-dependent spin-phonon coupling induced by the spin dynamics in EuO. PMID- 27203333 TI - Anomalous Wien Effects in Supercooled Ionic Liquids. AB - We have measured conductivity spectra of several supercooled monocationic and dicationic ionic liquids in the nonlinear regime by applying ac electric fields with large amplitudes up to about 180 kV/cm. Thereby, higher harmonic ac currents up to the 7th order were detected. Our results point to the existence of anomalous Wien effects in supercooled ionic liquids. Most ionic liquids studied here exhibit a conductivity-viscosity relation, which is close to the predictions of the Nernst-Einstein and Stokes-Einstein equations, as observed for classical strong electrolytes like KCl. These "strong" ionic liquids show a much stronger nonlinearity of the conductivity than classical strong electrolytes. On the other hand, the conductivity-viscosity relation of the ionic liquid [P_{6,6,6,14}][Cl] points to ion association effects. This "weak" ionic liquid shows a strength of the nonlinear effect, which is comparable to classical weak electrolytes. However, the nonlinearity increases quadratically with the field. We suggest that a theory for explaining these anomalies will have to go beyond the level of Coulomb lattice gas models. PMID- 27203334 TI - Spontaneous Charge Carrier Localization in Extended One-Dimensional Systems. AB - Charge carrier localization in extended atomic systems has been described previously as being driven by disorder, point defects, or distortions of the ionic lattice. Here we show for the first time by means of first-principles computations that charge carriers can spontaneously localize due to a purely electronic effect in otherwise perfectly ordered structures. Optimally tuned range-separated density functional theory and many-body perturbation calculations within the GW approximation reveal that in trans-polyacetylene and polythiophene the hole density localizes on a length scale of several nanometers. This is due to exchange-induced translational symmetry breaking of the charge density. Ionization potentials, optical absorption peaks, excitonic binding energies, and the optimally tuned range parameter itself all become independent of polymer length as it exceeds the critical localization length. Moreover, we find that lattice disorder and the formation of a polaron result from the charge localization in contrast to the traditional view that lattice distortions precede charge localization. Our results can explain experimental findings that polarons in conjugated polymers form instantaneously after exposure to ultrafast light pulses. PMID- 27203335 TI - Double Dirac Semimetals in Three Dimensions. AB - We study a class of Dirac semimetals that feature an eightfold-degenerate double Dirac point. We show that 7 of the 230 space groups can host such Dirac points and argue that they all generically display linear dispersion. We introduce an explicit tight-binding model for space groups 130 and 135. Space group 135 can host an intrinsic double Dirac semimetal with no additional states at the Fermi energy. This defines a symmetry-protected topological critical point, and we show that a uniaxial compressive strain applied in different directions leads to topologically distinct insulating phases. In addition, the double Dirac semimetal can accommodate topological line defects that bind helical modes. Connections are made to theories of strongly interacting filling-enforced semimetals, and potential materials realizations are discussed. PMID- 27203336 TI - Enhancement of Thermally Injected Spin Current through an Antiferromagnetic Insulator. AB - We report a large enhancement of thermally injected spin current in normal metal (NM)/antiferromagnet (AF)/yttrium iron garnet (YIG), where a thin AF insulating layer of NiO or CoO can enhance the spin current from YIG to a NM by up to a factor of 10. The spin current enhancement in NM/AF/YIG, with a pronounced maximum near the Neel temperature of the thin AF layer, has been found to scale linearly with the spin-mixing conductance at the NM/YIG interface for NM=3d, 4d, and 5d metals. Calculations of spin current enhancement and spin mixing conductance are qualitatively consistent with the experimental results. PMID- 27203337 TI - Electron Interference in Ballistic Graphene Nanoconstrictions. AB - We realize nanometer size constrictions in ballistic graphene nanoribbons grown on sidewalls of SiC mesa structures. The high quality of our devices allows the observation of a number of electronic quantum interference phenomena. The transmissions of Fabry-Perot-like resonances are probed by in situ transport measurements at various temperatures. The energies of the resonances are determined by the size of the constrictions, which can be controlled precisely using STM lithography. The temperature and size dependence of the measured conductances are in quantitative agreement with tight-binding calculations. The fact that these interference effects are visible even at room temperature makes the reported devices attractive as building blocks for future carbon based electronics. PMID- 27203338 TI - Phonon-Assisted Resonant Tunneling of Electrons in Graphene-Boron Nitride Transistors. AB - We observe a series of sharp resonant features in the differential conductance of graphene-hexagonal boron nitride-graphene tunnel transistors over a wide range of bias voltages between 10 and 200 mV. We attribute them to electron tunneling assisted by the emission of phonons of well-defined energy. The bias voltages at which they occur are insensitive to the applied gate voltage and hence independent of the carrier densities in the graphene electrodes, so plasmonic effects can be ruled out. The phonon energies corresponding to the resonances are compared with the lattice dispersion curves of graphene-boron nitride heterostructures and are close to peaks in the single phonon density of states. PMID- 27203339 TI - Anomalous Interlayer Transport of Quantum Hall Bilayers in the Strongly Josephson Coupled Regime. AB - We investigate Josephson coupling in a closely spaced quantum Hall bilayer. Reduction of the interlayer barrier from the widely used values of 10-12 nm to the present one of 8 nm leads to qualitatively different interlayer transport properties. The breakdown of interlayer coherence can be spatially confined in regions that are smaller than the device size. Such a spatial inhomogeneity depends crucially on the Josephson-coupling strength and can be removed by adding an in-plane magnetic field of about 0.5 T. At higher in-plane fields, the interlayer tunneling I-V curve develops unexpected overshoot features. These results challenge current theoretical understanding and suggest that our bilayer system has entered a previously unexplored regime. PMID- 27203340 TI - Sublattice Interference as the Origin of sigma Band Kinks in Graphene. AB - Kinks near the Fermi level observed in angle-resolved photoemission spectroscopy (ARPES) have been widely accepted to represent electronic coupling to collective excitations, but kinks at higher energies have eluded a unified description. We identify the mechanism leading to such kink features by means of ARPES and tight binding band calculations on sigma bands of graphene, where anomalous kinks at energies as high as ~4 eV were reported recently [Phys. Rev. Lett. 111, 216806 (2013)]. We found that two sigma bands show a strong intensity modulation with abruptly vanishing intensity near the kink features, which is due to sublattice interference. The interference induced local singularity in the matrix element is a critical factor that gives rise to apparent kink features, as confirmed by our spectral simulations without involving any coupling to collective excitations. PMID- 27203342 TI - Magnetic Vortex Induced by Nonmagnetic Impurity in Frustrated Magnets. AB - We study the effect of a nonmagnetic impurity inserted in a two-dimensional frustrated ferromagnet above its saturation magnetic field H_{sat} for arbitrary spin S. We demonstrate that the ground state includes a magnetic vortex that is nucleated around the impurity over a finite range of magnetic field H_{sat}<=H<=H_{sat}^{I}. Upon approaching the quantum critical point at H=H_{sat}, the radius of the magnetic vortex diverges as the magnetic correlation length: xi?1/sqrt[H-H_{sat}]. These results are derived both for the lattice and in the continuum limit. PMID- 27203341 TI - Giant Enhancement of Magnetic Anisotropy in Ultrathin Manganite Films via Nanoscale 1D Periodic Depth Modulation. AB - The relatively low magnetocrystalline anisotropy (MCA) in strongly correlated manganites (La,Sr)MnO_{3} has been a major hurdle for implementing them in spintronic applications. Here we report an unusual, giant enhancement of in-plane MCA in 6 nm La_{0.67}Sr_{0.33}MnO_{3} (LSMO) films grown on (001) SrTiO_{3} substrates when the top 2 nm is patterned into periodic stripes of 100 or 200 nm width. Planar Hall effect measurements reveal an emergent uniaxial anisotropy superimposed on one of the original biaxial easy axes for unpatterned LSMO along ?110? directions, with a 50-fold enhanced anisotropy energy density of 5.6*10^{6} erg/cm^{3} within the nanostripes, comparable to the value for cobalt. The magnitude and direction of the uniaxial anisotropy exclude shape anisotropy and the step edge effect as its origin. High resolution transmission electron microscopy studies reveal a nonequilibrium strain distribution and drastic suppression in the c-axis lattice constant within the nanostructures, which is the driving mechanism for the enhanced uniaxial MCA, as suggested by first principles density functional calculations. PMID- 27203343 TI - Anomalous Fluctuations of Nematic Order in Solutions of Semiflexible Polymers. AB - The nematic ordering in semiflexible polymers with contour length L exceeding their persistence length l_{p} is described by a confinement of the polymers in a cylinder of radius r_{eff} much larger than the radius r_{rho} expected from the respective concentration of the solution. Large-scale molecular dynamics simulations combined with density functional theory are used to locate the isotropic-nematic (I-N) transition and to validate this cylindrical confinement. Anomalous fluctuations due to chain deflections from neighboring chains in the nematic phase are proposed. Considering deflections as collective excitations in the nematically ordered phase of semiflexible polymers elucidates the origins of shortcomings in the description of the I-N transition by existing theories. PMID- 27203344 TI - Role of Turnover in Active Stress Generation in a Filament Network. AB - We study the effect of turnover of cross-linkers, motors, and filaments on the generation of a contractile stress in a network of filaments connected by passive cross-linkers and subjected to the forces exerted by molecular motors. We perform numerical simulations where filaments are treated as rigid rods and molecular motors move fast compared to the time scale of an exchange of cross-linkers. We show that molecular motors create a contractile stress above a critical number of cross-linkers. When passive cross-linkers are allowed to turn over, the stress exerted by the network vanishes due to the formation of clusters. When both filaments and passive cross-linkers turn over, clustering is prevented and the network reaches a dynamic contractile steady state. A maximum stress is reached for an optimum ratio of the filament and cross-linker turnover rates. Taken together, our work reveals conditions for stress generation by molecular motors in a fluid isotropic network of rearranging filaments. PMID- 27203345 TI - Rheological Signature of Frictional Interactions in Shear Thickening Suspensions. AB - Colloidal shear thickening presents a significant challenge because the macroscopic rheology becomes increasingly controlled by the microscopic details of short ranged particle interactions in the shear thickening regime. Our measurements here of the first normal stress difference over a wide range of particle volume fractions elucidate the relative contributions from hydrodynamic lubrication and frictional contact forces, which have been debated. At moderate volume fractions we find N_{1}<0, consistent with hydrodynamic models; however, at higher volume fractions and shear stresses these models break down and we instead observe dilation (N_{1}>0), indicating frictional contact networks. Remarkably, there is no signature of this transition in the viscosity; instead, this change in the sign of N_{1} occurs while the shear thickening remains continuous. These results suggest a scenario where shear thickening is driven primarily by the formation of frictional contacts, with hydrodynamic forces playing a supporting role at lower concentrations. Motivated by this picture, we introduce a simple model that combines these frictional and hydrodynamic contributions and accurately fits the measured viscosity over a wide range of particle volume fractions and shear stress. PMID- 27203346 TI - Universal Cyclic Topology in Polymer Networks. AB - Polymer networks invariably possess topological defects: loops of different orders which have profound effects on network properties. Here, we demonstrate that all cyclic topologies are a universal function of a single dimensionless parameter characterizing the conditions for network formation. The theory is in excellent agreement with both experimental measurements of hydrogel loop fractions and Monte Carlo simulations without any fitting parameters. We demonstrate the superposition of the dilution effect and chain-length effect on loop formation. The one-to-one correspondence between the network topology and primary loop fraction demonstrates that the entire network topology is characterized by measurement of just primary loops, a single chain topological feature. Different cyclic defects cannot vary independently, in contrast to the intuition that the densities of all topological species are freely adjustable. Quantifying these defects facilitates studying the correlations between the topology and properties of polymer networks, providing a key step in overcoming an outstanding challenge in polymer physics. PMID- 27203347 TI - Thermo-Osmotic Flow in Thin Films. AB - We report on the first microscale observation of the velocity field imposed by a nonuniform heat content along the solid-liquid boundary. We determine both radial and vertical velocity components of this thermo-osmotic flow field by tracking single tracer nanoparticles. The measured flow profiles are compared to an approximate analytical theory and to numerical calculations. From the measured slip velocity we deduce the thermo-osmotic coefficient for both bare glass and Pluronic F-127 covered surfaces. The value for Pluronic F-127 agrees well with Soret data for polyethylene glycol, whereas that for glass differs from literature values and indicates the complex boundary layer thermodynamics of glass-water interfaces. PMID- 27203348 TI - Comment on "Anomalous Discontinuity at the Percolation Critical Point of Active Gels". PMID- 27203349 TI - Sheinman, Sharma, and MacKintosh Reply. PMID- 27203350 TI - Publisher's Note: Haldane-Hubbard Mott insulator: From Tetrahedral Spin Crystal to Chiral Spin Liquid [Phys. Rev. Lett. 116, 137202 (2016)]. AB - This corrects the article DOI: 10.1103/PhysRevLett.116.137202. PMID- 27203351 TI - Erratum: Signatures for Wigner Crystal Formation in the Chemical Potential of a Two-Dimensional Electron System [Phys. Rev. Lett. 113, 076804 (2014)]. AB - This corrects the article DOI: 10.1103/PhysRevLett.113.076804. PMID- 27203352 TI - Erratum: Analytic Form of the Two-Loop Planar Five-Gluon All-Plus-Helicity Amplitude in QCD [Phys. Rev. Lett. 116, 062001 (2016)]. AB - This corrects the article DOI: 10.1103/PhysRevLett.116.062001. PMID- 27203353 TI - The accuracy of telling time via oscillatory signals. AB - Circadian clocks are the central timekeepers of life, allowing cells to anticipate changes between day and night. Experiments in recent years have revealed that circadian clocks can be highly stable, raising the question how reliably they can be read out. Here, we combine mathematical modeling with information theory to address the question how accurately a cell can infer the time from an ensemble of protein oscillations, which are driven by a circadian clock. We show that the precision increases with the number of oscillations and their amplitude relative to their noise. Our analysis also reveals that their exists an optimal phase relation that minimizes the error in the estimate of time, which depends on the relative noise levels of the protein oscillations. Lastly, our work shows that cross-correlations in the noise of the protein oscillations can enhance the mutual information, which suggests that cross regulatory interactions between the proteins that read out the clock can be beneficial for temporal information transmission. PMID- 27203354 TI - Drug-Resistant and Genetic Evolutionary Analysis of Influenza Virus from Patients During the 2013 and 2014 Influenza Season in Beijing. AB - The study aimed to analyze drug resistance and mutations and genetic evolution of influenza A and influenza B viruses during the 2013 and 2014 influenza season in Beijing, China. RNA was extracted from pharyngeal or nasal swabs of 28 patients, and determination of influenza genotypes was performed by using real-time reverse transcription polymerase chain reaction. Influenza A virus samples were sequenced with the neuraminidase (NA) gene and M2 matrix protein gene to determine the NA inhibitor (NAI) resistance and amantadine resistance mutations, and influenza B virus samples were sequenced with the NA gene and hemagglutinin (HA) gene to analyze NAI resistance mutations. As a result, the enrolled subjects consisted of 19 patients with the A(H1N1)pdm09 subtype, four with A(H3N2) subtype and five with influenza B virus. All of the 23 samples with influenza A viruses harbored amantadine resistance mutation S31N in M2 matrix protein. V241I, a compensatory NAI resistance mutation, was detected in all of the 19 A(H1N1)pdm09 viruses. No other NAI resistance mutation was observed in both influenza A and B viruses. The NA gene of the five influenza B virus strains was classified as B-Victoria lineage, while the HA gene of five strains was classified as B-Yamagata lineage. In summary, all influenza A viruses from patients in Beijing in the 2013-2014 season were resistant to amantadine agent. Both influenza A and B viruses kept sensitive to NAIs. Lineage recombination was detected in influenza B virus strains and may impair the efficacy of influenza vaccination. PMID- 27203355 TI - High-throughput production of a stable isotope-labeled peptide library for targeted proteomics using a wheat germ cell-free synthesis system. AB - Quantitative proteomic approaches using selected reaction monitoring (SRM) are currently limited by the difficulty in the preparation of reference standards. In this study, we demonstrat the high-throughput production of a reference peptide library using a wheat germ cell-free synthesis system to develop a large-scale SRM assay for targeted proteomics. PMID- 27203356 TI - Characterization of Yersinia enterocolitica strains potentially virulent for humans and animals in river water. AB - AIMS: The aim of this study was to isolate and identify potentially pathogenic strains of Yersinia enterocolitica in water samples collected from the upstream section of the Drweca River in Poland. METHODS AND RESULTS: Thirty-nine water samples were collected. Strains were isolated, identified with the use of the API((r)) 20E test kit (Biomerieux, Marcy l'Etoile, France) at 37 degrees C, serotyped and subjected to a molecular analysis. Multiplex PCR was carried out to amplify three virulence genes: ail, ystA and ystB. Fragments of ail and ystA genes were not identified in the genetic material of the analysed strains. The ystB gene was identified in four strains. Yersinia enterocolitica strains of biotype 1A, which contain the ystB gene, may cause gastrointestinal problems. CONCLUSIONS: In our study, Y. enterocolitica strains of biotype 1A/ystB with serotypes 0 : 3, 0 : 5 and 0 : 8 were identified in samples collected from the Drweca River which flows through the areas protected by Natura 2000, one of the largest networks of nature conservation areas in the European Union. The presence of Y. enterocolitica in the Drweca River indicates that the analysed bacteria colonize natural water bodies. SIGNIFICANCE AND IMPACT OF THE STUDY: Most research focuses on food or sewage as a source of Y. enterocolitica infections. Little is known about the occurrence of this pathogen in natural waters. Our results show that natural waters are also a potential threat to human and animal health. PMID- 27203358 TI - Nuclear Quantum Effects in Water at the Triple Point: Using Theory as a Link Between Experiments. AB - One of the most prominent consequences of the quantum nature of light atomic nuclei is that their kinetic energy does not follow a Maxwell-Boltzmann distribution. Deep inelastic neutron scattering (DINS) experiments can measure this effect. Thus, the nuclear quantum kinetic energy can be probed directly in both ordered and disordered samples. However, the relation between the quantum kinetic energy and the atomic environment is a very indirect one, and cross validation with theoretical modeling is therefore urgently needed. Here, we use state of the art path integral molecular dynamics techniques to compute the kinetic energy of hydrogen and oxygen nuclei in liquid, solid, and gas-phase water close to the triple point, comparing three different interatomic potentials and validating our results against equilibrium isotope fractionation measurements. We will then show how accurate simulations can draw a link between extremely precise fractionation experiments and DINS, therefore establishing a reliable benchmark for future measurements and providing key insights to increase further the accuracy of interatomic potentials for water. PMID- 27203357 TI - Hydrophilic Clicked 2,6-Bis-triazolyl-pyridines Endowed with High Actinide Selectivity and Radiochemical Stability: Toward a Closed Nuclear Fuel Cycle. AB - There is still an evident need for selective and stable ligands able to separate actinide(III) from lanthanide(III) metal ions in view of the treatment of the accumulated radioactive waste and of the recycling of minor actinides. We have herein demonstrated that hydrophilic 2,6-bis-triazolyl-pyridines are able to strip all actinides in all the different oxidation states from a diglycolamide containing kerosene solution into an acidic aqueous phase. The ascertained high actinide selectivity, efficiency, extraction kinetics, and chemical/radiolytic stability spotlight this hydrophilic class of ligands as exceptional candidates for advanced separation processes fundamental for closing the nuclear fuel cycle and solving the environmental issues related to the management of existing nuclear waste. PMID- 27203359 TI - Coordination polymer gels: soft metal-organic supramolecular materials and versatile applications. AB - In recent times, significant attention has been paid to the development of functional coordination polymer gels (CPGs) from rationally designed low molecular weight gelators (LMWGs) and metal ions. Coordination of metal ions to LMWGs provides an opportunity to emulate metal based redox, optical, electronic and magnetic properties in soft CPG materials. The metal-LMWG interactions allow controlled growth of CPGs with different nanostructures such as fibers, tubes, rings, ribbons and vesicles. Furthermore, the nanoscale periodicity of metal ions and LWMGs in CPGs is of paramount importance for different optoelectronic applications. The easy processability and dynamic nature of CPGs are explored for application in diverse fields, including drug-delivery, gas storage, optoelectronics, chemo-sensing, self-healing, etc. Also, by taking advantage of dynamic metal-ligand coordination bonds various stimuli-responsive multi functional CPGs are developed. In this feature article, we cover important examples of newly developed CPGs, which show potential applications in different fields. PMID- 27203360 TI - Electrochemical decompatibilisation leads to morphology rearrangements in host guest polymer blend films. AB - Controlled phase separation in a polymer film, with subsequent morphology rearrangement on the micro-scale, provides novel perspectives in smart materials. Based on our experience on supramolecularly compatibilised polymer blends consisting of polystyrene and poly(butyl methacrylate), we demonstrate here physical segregation of the blend in the solid state by the application of an electrochemical stimulus. The thereby occurring changes in film morphology, namely the appearance of voids and grains, have been characterised by atomic force microscopy in spin coated and in Langmuir-Schaefer deposited films. PMID- 27203361 TI - Increased overall drug utilization in patients with psoriasis: a case-control study based on Dutch general practitioner data. AB - BACKGROUND: Medication use in patients with psoriasis has been studied mostly in the context of psoriasis comorbidities. OBJECTIVES: To investigate detailed drug utilization in patients with psoriasis compared with controls in a population based sample. METHODS: This was a case-control study based on drug prescriptions derived from a Dutch general practitioner database where patients with psoriasis and controls without psoriasis were matched 1 : 1 for age, sex, general practitioner and duration of follow-up, between 2002 and 2012. We calculated Mantel-Haenszel odds ratios (ORs) and 95% confidence intervals (CIs) for all therapeutic groups and chemical substances. RESULTS: In total 17 627 patients with psoriasis and 17 627 controls were followed for > 4 years. Overall 20% of patients with psoriasis received no psoriasis treatment and 8% had moderate-to severe disease. During the entire follow-up a mean of nine unique drugs were prescribed in patients with psoriasis; this was significantly higher than in controls (mean of seven). Drug use did not peak around the date of diagnosis for psoriasis, but remained constant over time. All of the most commonly prescribed therapeutic groups were significantly more often prescribed in patients with psoriasis than in controls. These included drugs associated with psoriasis symptoms and treatment (OR 2.17, 95% CI 2.07-2.28 and OR 22, 95% CI 21-25, respectively), drugs related to psoriasis comorbidities (1.46, 95% CI 1.39-1.53) and a proportion of drugs that were a priori not expected to be increased in patients with psoriasis, such as nasal preparations and laxatives. CONCLUSIONS: Patients with psoriasis received more prescriptions for all drugs, regardless of associated comorbidities. This overall increased use of drugs suggests an increased healthcare utilization in patients with psoriasis identified in routine databases. PMID- 27203362 TI - Comparison of impedance measurements near the skin of newborns and adults. AB - Electrical impedance tomography (EIT) is a non-invasive imaging technology that has been extensively studied for monitoring lung function of neonatal and adult subjects, especially in neonatal intensive care unit (NICU) and intensive care unit (ICU) environments. The sources of the total impedance in these applications include internal organs, near-boundary tissues, electrode-skin impedance, electrodes and conducting wires. This total impedance must be considered for system design and setting voltage gain since it will contribute to the measured voltage. To adapt a single instrument for use on infants and adults, we studied the difference between the impedance near the skin in both classes of patients. We used a simultaneous multi-source EIT (SMS-EIT) system to make impedance measurements. Characteristic resistance was calculated for two different current patterns: one that is more sensitive to boundary region impedance and another that is more sensitive to interior changes. We present ratios of these resistances to assess the relative contribution of near-skin effects to the overall impedance. Twenty adult ICU subjects (10 male, 10 female, age: 49.05 +/- 16.32 years (mean +/- standard deviation)) and 45 neonates (23 male, 22 female, gestational age: 37.67 +/- 2.11 weeks, postnatal age, 2.56 +/- 2.67 d) were studied at Columbia University Medical Center. Impedance measurements at 10 kHz were collected for approximately one hour from each subject. The characteristic resistance ratio for each subject was computed and analyzed. The result shows the impedance at or near the skin of newborns is significantly higher than in adult subjects. PMID- 27203363 TI - Biomechanical effect of the correction on the anchoring strength of de-orbiting S1 bicortical pedicle screw - An in-vitro investigation in normal and osteoporotic conditions. PMID- 27203364 TI - Trocars: Site Selection, Instrumentation, and Overcoming Complications. AB - In recent years, laparoscopy and robot-assisted procedures have become more commonplace in urology. Incorporation of these techniques into clinical practice requires extensive knowledge of the surgical approaches and complex instrumentation unique to minimally invasive surgery. In this review, focus will be directed to laparoscopic trocars including differing subtypes, placement in select urologic procedures, and proper use with emphasis on the avoidance of complications. Differing methods for the development of pneumoperitoneum and the associated risks of each will be discussed. The aim of this article is to provide a complete review of laparoscopic trocar use for the practicing urologist. PMID- 27203366 TI - Application of the system of environmental economic accounting for water SEEAW to the Spanish part of the Duero basin: Lessons learned. AB - The System of Environmental-Economic Accounting for Water (SEEA-W) consists of an agreed international framework for organizing hydrological and economic information in a coherent and consistent manner. The methodology yields to the SEEA-W physical tables focusing on the quantitative assessment of the stocks and their changes in a river basin during the accounting period. For that purpose, the information on the abstraction and water discharge is linked with the environment water stocks, which assesses how current levels of abstraction and discharge affect such water stocks. This study presents the methodology and results to fill out the SEEAW tables for asset accounts on the Spanish Duero basin. Duero is a transboundary river between Spain and Portugal where 80% of its basin area (78,860km(2)) runs into the Spanish territory. The Spanish part is divided in five zones and 13 management systems. The methodology applied the three models used by the Spanish Water Authorities for the planning and allocation of water resources in Spain: 'SIMPA' model (rainfall-runoff model), 'ASTER' model (hydro-meteorological model related to snow processes) and 'SIMGES' model (water management simulation model). The required information was collected with the support from the Duero River basin Authority and the Spanish Ministry of Agriculture. Special care was paid to issues such as: inter-annual variability, the selection of spatial and temporal scale, seasonality, disaggregation of human abstractions into use's type, and transboundary agreements. The results highlighted some drawbacks in the SEEAW methodology for the Duero basin. However, the developed balances are a valuable tool to support the decisions of the Spanish Duero basin Authority on the management and allocation of water in the basin and in the transboundary area with Portugal. Finally, the paper outlines some recommendations for future work. PMID- 27203365 TI - Characterization of a crude oil weathering series by ultrahigh-resolution mass spectrometry using multiple ionization modes. AB - Accidental crude oil releases, such as the Deepwater Horizon (DWH) accident, are always a potential threat to pristine marine ecosystems. Since the toxicity of crude oil heavily depends on its variable composition, the comprehensive characterization of crude oil compounds as a function of weathering is an important area of research. Traditional gas chromatography-based characterization presents significant limitations, and the use of ultrahigh-resolution mass spectrometric (UHRMS) techniques (that allow for the assignment of molecular formulae) has been shown to be better equipped to address the complex nature of crude oils. This study used an Orbitrap Q Exactive mass spectrometer operated at a resolving power of 140,000FWHM with both electrospray ionization (ESI) and atmospheric pressure photoionization (APPI) sources, in order to characterize a crude oil weathering series of the Macondo oil released during the DWH incident (the source oil, two differently weathered surface slicks, and a beached residue). Preliminary gas chromatography mass spectrometry (GC-MS) and gas chromatography flame ionization detection (GC-FID) results suggested that the four oils comprised a true weathering series (including biodegradation and photodegradation in addition to other well-known processes such as dissolution and evaporation). UHRMS results showed a clear increase in oxygenated compounds with weathering, and further suggested a significant gain of acidic compounds, as well as the transformation of phenols to ketonic and quinonic compounds with weathering. A complementary study on a weathered oil sample amended with selected model compounds contributed additional insight into the functional group types that are accessible in each ionization technique. PMID- 27203367 TI - On the influence of spread constant in radial basis networks for electrical impedance tomography. AB - Electrical impedance tomography (EIT) is a non-invasive imaging technique. The main task of this work is to solve a non-linear inverse problem, for which several techniques have been suggested, but none of which gives a very high degree of accuracy. This paper introduces a novel approach, based on radial basis function (RBF) artificial neural networks (ANNs), to solve this problem, and uses several ANNs to obtain the best solution to the EIT inverse problem. ANNs have the potential to directly estimate the solution of the inverse problem with a high degree of accuracy. While different radial basis neural networks do not always perform well on different problems, they usually give good results on some specific problems. This paper evidences a strong correlation between the area of the target and the spread constant of the RBF network that gives the best reconstruction. A solution to automatically estimate the size of the target and pick the best neural network directly from voltage measurements is presented, making the reconstruction process automatic. By automatically selecting the best ANN for each specific set of voltage measurements, the proposed solution gives a more accurate reconstruction of both small and large targets. PMID- 27203368 TI - Health-Related Quality of Life in Survivors of High-Risk Neuroblastoma After Stem Cell Transplant: A National Population-Based Perspective. AB - PURPOSE: This study aimed to estimate the burden of morbidity, in terms of health related quality of life (HRQL), in survivors of high-risk neuroblastoma (NBL) after myeloablative chemotherapy followed by autologous hematopoietic stem cell transplant (HSCT). PATIENTS AND METHODS: A national population-based survey was undertaken of survivors of high-risk NBL (N = 99), diagnosed between 1991 and 2010 and treated with HSCT. Parents completed a proxy questionnaire incorporating two HRQL measures, Health Utilities Index (HUI) 2 and 3. Children >12 years of age provided self-assessments. Clinical and demographic data were collected. Independent t-test and one-way analysis of variance were used to assess differences. Comparative data were obtained from previously published work and Statistics Canada's 1998 National Population Health Survey. RESULTS: On a scale of 0 (being dead) to 1.0 (perfect health), mean HRQL utility scores were 0.89 (SD = 0.11) in HUI2 and 0.84 (SD = 0.18) in HUI3. Parents reported morbidity in sensation (52.5%), pain (30.3%), cognition (28.0%), and emotion (24.2%) in HUI2 and in hearing (38.4%), pain (30.3%), cognition (27.3%), and speech (23.2%) in HUI3. HRQL was not significantly different compared to NBL survivors treated without HSCT, but was less than in nontransplanted survivors of acute lymphoblastic leukemia and Wilms tumor, and children in the general population, yet higher than in survivors of brain tumors. CONCLUSIONS: HRQL is compromised in high-risk NBL survivors treated with and without HSCT. A differential effect on hearing reflects additional exposure to platinum-based chemotherapy. These results should inform long-term care and the development of new therapeutic interventions. PMID- 27203369 TI - Of Tangerines, Asparagus, and Nonprotein Biomolecules. AB - Every month the editors of Cell Chemical Biology bring you highlights of the most recent chemical biology literature. Our May 2016 selection includes a new method for labeling and visualizing nonprotein biomolecules using electron microscopy; a small molecule, originally found in tangerine peel, that regulates our circadian clock and helps with some of the metabolic pathologies associated with circadian rhythms; and a finding that asparagine is used as an amino acid exchanger in tumor cells. PMID- 27203370 TI - Light-Activated Chemotaxis. AB - Using light to control cellular processes is one of the attractive areas of research. Here, availability of different, light-responsive caged compounds has played a critical role. In this issue of Cell Chemical Biology, Hovelmann et al. (2016) give us an example of how to design and use caged lipids to guide chemotaxis at the single cell level. PMID- 27203371 TI - Chemical-Induced Naive Pluripotency. AB - The capacity to harness the properties of pluripotent stem cells has a wide reaching impact on regenerative medicine, drug discovery, and also basic science. Two recent publications by Ursu et al. and Illich et al. demonstrate that inhibition of a CK1 isoform efficiently induces naive pluripotency in epiblast stem cells. PMID- 27203372 TI - Cracking the Nonribosomal Code. AB - Landmark achievements in chemical and structural biology have advanced our understanding of nonribosomal peptide synthetase mechanisms. However, nature's proven ability to re-engineer these enzymes remains difficult to recapitulate synthetically. In a recent issue of Cell Chemical Biology, Meyer et al. (2016) sought to extract new clues from old (evolutionary) evidence. PMID- 27203373 TI - Linking Nucleoporins, Mitosis, and Colon Cancer. AB - Suppression of a nuclear pore protein Nup358/RanBP2 is linked to mitotic cell death, but the clinical relevance of this link is unknown. In a recent issue of Cell, Vecchione et al. (2016) show that in approximately 10% of BRAF-like colorectal cancer (CC) patients, Nup358/RanBP2 is critical for survival. Treatment with vinorelbine, a microtubule-depolymerizing drug that inhibits mitosis, might be a potential treatment for these CCs. PMID- 27203374 TI - The Structural Relationship between Iterative and Modular PKSs. AB - Recent work has characterized the architecture of a highly-reducing iterative polyketide synthase (PKS), the mycocerosic acid synthase (MAS) (Herbst et al., 2016). Beyond sharing a structural similarity with the mammalian fatty acid synthase (FAS), the authors argue that the MAS architecture is representative of some PKS modules. PMID- 27203375 TI - Scratching the Surface: Resurfacing Proteins to Endow New Properties and Function. AB - Protein engineering is an emerging discipline that dovetails modern molecular biology techniques with high-throughput screening, laboratory evolution technologies, and computational approaches to modify sequence, structure, and, in some cases, function and properties of proteins. The ultimate goal is to develop new proteins with improved or designer functions for use in biotechnology, medicine, and basic research. One way to engineer proteins is to change their solvent-exposed regions through focused or random "protein resurfacing." In this review we explain what protein resurfacing is, and discuss recent examples of how this strategy is used to generate proteins with altered or broadened recognition profiles, improved stability, solubility, and expression, cell-penetrating ability, and reduced immunogenicity. Additionally we comment on how these properties can be further improved using chemical resurfacing approaches. Protein resurfacing will likely play an increasingly important role as more biologics enter clinical use, and we present some arguments to support this view. PMID- 27203376 TI - Apratoxin Kills Cells by Direct Blockade of the Sec61 Protein Translocation Channel. AB - Apratoxin A is a cytotoxic natural product that prevents the biogenesis of secretory and membrane proteins. Biochemically, apratoxin A inhibits cotranslational translocation into the ER, but its cellular target and mechanism of action have remained controversial. Here, we demonstrate that apratoxin A prevents protein translocation by directly targeting Sec61alpha, the central subunit of the protein translocation channel. Mutagenesis and competitive photo crosslinking studies indicate that apratoxin A binds to the Sec61 lateral gate in a manner that differs from cotransin, a substrate-selective Sec61 inhibitor. In contrast to cotransin, apratoxin A does not exhibit a substrate-selective inhibitory mechanism, but blocks ER translocation of all tested Sec61 clients with similar potency. Our results suggest that multiple structurally unrelated natural products have evolved to target overlapping but non-identical binding sites on Sec61, thereby producing distinct biological outcomes. PMID- 27203378 TI - Effect of Hatha Yoga on Anxiety: A Meta-Analysis. AB - OBJECTIVE: Some evidence suggests that Hatha yoga might be an effective practice to reduce anxiety. To examine the effect of Hatha yoga on anxiety, we conducted a meta-analysis of relevant studies extracted from PubMed, PsycINFO, the Cochrane Library, and manual searches. METHODS: The search identified 17 studies (11 waitlist controlled trials) totaling 501 participants who received Hatha yoga and who reported their levels of anxiety before and after the practice. We estimated the controlled and within-group random effects of the practice on anxiety. RESULTS: The pre-post within-group and controlled effect sizes were, Hedges' g = 0.44 and Hedges' g = 0.61, respectively. Treatment efficacy was positively associated with the total number of hours practiced. People with elevated levels of anxiety benefitted the most. Effect sizes were not moderated by study year, gender, presence of a medical disorder, or age. Although the quality of the studies was relatively low, the risk of study bias did not moderate the effect. CONCLUSIONS: Hatha yoga is a promising method for treating anxiety. However, more well-controlled studies are needed to compare the efficacy of Hatha yoga with other more established treatments and to understand its mechanism. This article is protected by copyright. All rights reserved. PMID- 27203379 TI - Conceptualizing primary and secondary pathological exercise using available measures of excessive exercise. AB - OBJECTIVE: There is disagreement about the conceptualization and measurement of pathological exercise (PE). This study seeks to elucidate the nature of this phenomenon as addictive or compulsive in its primary and secondary forms. METHOD: 1,497 adults (608 men, 885 women, 4 other) completed a set of validated surveys, including the Godin Leisure-Time Exercise Questionnaire, the Exercise Dependence Scale-21, the Exercise Addiction Inventory, the Compulsive Exercise Test (CET), the Obligatory Exercise Questionnaire, the Commitment to Exercise Scale, and an exercise specific adaptation of the Dimensional Obsessive-Compulsive Scale (ESDOCS). Participants completed the Eating Disorders Examination Questionnaire, and DSM-5 eating disorder (ED) diagnoses were determined according to published guidelines. Pearson correlation coefficients, independent samples t-tests, chi(2) tests, 1-way ANOVA's, and ANCOVA's were calculated. RESULTS: All PE measures correlated highly with one another (P < 0.001). Participants with EDs scored higher on all measures than those without (P < 0.001), and those with bulimia nervosa had the highest scores. Participants with PE and an accompanying ED (secondary PE) scored higher than those with PE and no ED symptoms (primary ED) on the CET (P < 0.002) and ESDOCS (P < 0.003). Correlations between EDE-Q and PE scores were stronger among women than men. PE prevalence was 6.4% (1.4% primary PE, 5.0% secondary PE) in our heterogeneous sample. DISCUSSION: Secondary PE appears to be more compulsive while primary PE is more addictive in nature. Men and women are equally at risk for PE, but in men it is more often primary and addictive and in women it is more often secondary and compulsive. (c) 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:778-792). PMID- 27203377 TI - Controlling Sulfuryl-Transfer Biology. AB - In humans, the cytosolic sulfotransferases (SULTs) catalyze regiospecific transfer of the sulfuryl moiety (-SO3) from 3'-phosphoadenosine 5'-phosphosulfate to thousands of metabolites, including numerous signaling small molecules, and thus regulates their activities and half-lives. Imbalances in the in vivo set points of these reactions leads to disease. Here, with the goal of controlling sulfonation in vivo, molecular ligand-recognition principles in the SULT and nuclear receptor families are integrated in creating a strategy that can prevent sulfonation of a compound without significantly altering its receptor affinity, or inhibiting SULTS. The strategy is validated by using it to control the sulfonation and estrogen receptor (ER) activating activity of raloxifene (a US Food and Drug Administration-approved selective estrogen receptor modulator) and its derivatives. Preventing sulfonation is shown to enhance ER-activation efficacy 10(4)-fold in studies using Ishikawa cells. The strategy offers the opportunity to control sulfuryl transfer on a compound-by-compound basis, to enhance the efficacy of sulfonated drugs, and to explore the biology of sulfuryl transfer with unprecedented precision. PMID- 27203380 TI - The apoptotic effect and the plausible mechanism of microwave radiation on rat myocardial cells. AB - Microwaves may exert adverse biological effects on the cardiovascular system at the integrated system and cellular levels. However, the mechanism underlying such effects remains poorly understood. Here, we report a previously uncharacterized mechanism through which microwaves damage myocardial cells. Rats were treated with 2450 MHz microwave radiation at 50, 100, 150, or 200 mW/cm(2) for 6 min. Microwave treatment significantly enhanced the levels of various enzymes in serum. In addition, it increased the malondialdehyde content while decreasing the levels of antioxidative stress enzymes, activities of enzyme complexes I-IV, and ATP in myocardial tissues. Notably, irradiated myocardial cells exhibited structural damage and underwent apoptosis. Furthermore, Western blot analysis revealed significant changes in expression levels of proteins involved in oxidative stress regulation and apoptotic signaling pathways, indicating that microwave irradiation could induce myocardial cell apoptosis by interfering with oxidative stress and cardiac energy metabolism. Our findings provide useful insights into the mechanism of microwave-induced damage to the cardiovascular system. PMID- 27203381 TI - 3-(3,4,5-Trimethoxybenzylidene)-2,4-pentanedione: Design of a novel photostabilizer with in vivo SPF boosting properties and its use in developing broad-spectrum sunscreen formulations. AB - OBJECTIVE: The study concerned the synthesis of a novel photostabilizer based on benzylidenepentanedione chemistry and the evaluation of its potential in developing a broad-spectrum sunscreen formulation containing avobenzone. METHODS: 3-(3,4,5-Trimethoxybenzylidene)-2-4-pentanedione (TMBP) was synthesized through a condensation reaction and incorporated into a sunscreen formulation containing, inter alia, avobenzone. The SPF, critical wavelength and in vitro photostability of the product were measured. The photostability was compared with that afforded by current avobenzone photostabilizers, namely octocrylene, ethylhexylmethoxycrylene and diethylhexylsyringylidenemalonate. The photostability of TMBP either alone or in the presence of avobenzone in a methanolic solution was also evaluated by UV spectrophotometric and HPLC analyses. The optical properties of TMBP were estimated experimentally and supported by time-dependent density functional theory (TD-DFT) calculations. RESULTS: The ability of TMBP to stabilize avobenzone under ultraviolet (UV) light exposure was shown both in formulated products and in solution. A comparative stability study incorporating various combinations of avobenzone, TMBP (vs. three commercial photostabilizers) and UVB sunscreens clearly showed TMBP to be a very effective stabilizer. The photostabilizing effect of TMBP arises from triplet state energy transfer from avobenzone to TMBP and through light-induced reactions that preserve the main chromophores. Interestingly, a 50% in vivo SPF boosting was observed when TMBP was used with organic and inorganic sunscreens when alone it has no contribution to SPF. TMBP-containing sunscreen formulations clearly showed a critical wavelength of well over 370 nm and can thus be categorized as broad-spectrum sunscreens. CONCLUSION: We were able to design a very effective photostabilizer, trimethoxybenzylidene pentanedione (INCI name), based on benzylidenepentanedione chemistry. TMBP is very efficient in stabilizing avobenzone in formulated products and boosts in vivo SPF by >50% for organic and inorganic sunscreens, and the formulations have critical wavelengths of >370 nm. These efficacious properties make it a promising additive for inclusion in broad spectrum photoprotective products. PMID- 27203382 TI - Load release balance test under unstable conditions effectively discriminates between physically active and sedentary young adults. AB - This study investigates test-retest reliability and diagnostic accuracy of the load release balance test under four varied conditions. Young, early and late middle-aged physically active and sedentary subjects performed the test over 2 testing sessions spaced 1week apart while standing on either (1) a stable or (2) an unstable surface with (3) eyes open (EO) and (4) eyes closed (EC), respectively. Results identified that test-retest reliability of parameters of the load release balance test was good to excellent, with high values of ICC (0.78-0.92) and low SEM (7.1%-10.7%). The peak and the time to peak posterior center of pressure (CoP) displacement were significantly lower in physically active as compared to sedentary young adults (21.6% and 21.0%) and early middle aged adults (22.0% and 20.9%) while standing on a foam surface with EO, and in late middle-aged adults on both unstable (25.6% and 24.5%) and stable support surfaces with EO (20.4% and 20.0%). The area under the ROC curve >0.80 for these variables indicates good discriminatory accuracy. Thus, these variables of the load release balance test measured under unstable conditions have the ability to differentiate between groups of physically active and sedentary adults as early as from 19years of age. PMID- 27203383 TI - Gyroscope-Like Complexes Based on Dibridgehead Diphosphine Cages That Are Accessed by Three-Fold Intramolecular Ring Closing Metatheses and Encase Fe(CO)3, Fe(CO)2(NO)(+), and Fe(CO)3(H)(+) Rotators. AB - Reactions of trans-Fe(CO)3(P((CH2)mCH?CH2)3)2 (m = a/4; b/5, c/6, e/8) and Grubbs' catalyst (12-24 mol %, CH2Cl2, reflux) give the cage-like trienes trans- Fe(CO)3(P((CH2)mCH?CH(CH2)m)3 P) (3a-c,e, 60-81%). Hydrogenations (ClRh(PPh3)3, 60-80 degrees C) yield the title compounds trans- Fe(CO)3(P((CH2)n)3 P) (4a-c,e, 74-86%; n = 2m + 2), which have idealized D3h symmetry. A crystal structure of 4c suggests enough van der Waals clearance for the Fe(CO)3 moiety to rotate within the three P(CH2)14P linkages; structures of E,E,E-3a show rotation to be blocked by the shorter P(CH2)4CH?CH(CH2)4P linkages. Additions of NO(+)BF4(-) give the isoelectronic and isosteric cations [ Fe(CO)2(NO)(P((CH2)n)3 P)](+)BF4(-) (5a c(+)BF4(-); 81-98%). Additions of [H(OEt2)2](+)BArf(-) (BArf = B(3,5 C6H3(CF3)2)4) afford the metal hydride complexes mer,trans-[ Fe(CO)3(H)(P((CH2)n)3 P)](+)BArf(-) (6a-c,e(+)BArf(-); 98-99%). The behavior of the rotators in the preceding complexes is probed by VT NMR. At ambient temperature in solution, 5a,b(+)BF4(-) and 6a(+)BArf(-) show two sets of P(CH2)n/2 (13)C NMR signals (2:1), whereas 5c(+)BF4(-) and 6b,c(+)BArf(-) show only one. At higher temperatures, the signals of 5b(+)BF4(-) coalesce; at lower temperatures, those of 5c(+)BF4(-) and 6b(+)BArf(-) decoalesce. These data give DeltaH(?)/DeltaS(?) values (kcal/mol and eu) of 8.3/-28.4 and 9.5/-6.5 for Fe(CO)2(NO)(+) rotation (5b,c(+)) and 6.1/-23.5 for Fe(CO)3(H)(+) rotation (6b(+)). (13)C CP/MAS NMR spectra show that the Fe(CO)3 moiety in polycrystalline 4c (but not 4a) undergoes rapid rotation between -60 and 95 degrees C. Approaches to minimizing these barriers and developing molecular gyroscopes are discussed. PMID- 27203384 TI - The novel VEGF receptor 2 inhibitor YLL545 inhibits angiogenesis and growth in breast cancer. AB - Their antiangiogenic effects make vascular endothelial growth factor receptor 2 (VEGFR2) inhibitors useful for cancer treatment. However, most of these drugs have unexpected adverse side effects. Here, we show that the novel VEGFR2 inhibitor YLL545 suppressed tumor angiogenesis and growth in triple-negative breast cancer without adverse effects. YLL545 treatment also markedly inhibited proliferation, migration, invasion, and tube formation by human umbilical vascular endothelial cells (HUVECs) in vitro. These effects of YLL545 were equal to or greater than those seen with sorafenib. In addition, YLL545 inhibited VEGF induced phosphorylation of VEGFR2 and activation of downstream signaling regulators, such as phospho-STAT3 and phospho-ERK1/2, in HUVECs. Embryonic angiogenesis assays in zebrafish and Matrigel plug assays in mice demonstrated that YLL545 inhibits angiogenesis in vivo. YLL545 also inhibited proliferation and induced apoptosis in MDA-MB-231 breast cancer cells both in vitro and in vivo, and 50 mg/kg/d YLL545 inhibited human tumor xenograft growth by more than 50% in BALB/c nude mice. These observations suggest YLL545 is a potentially useful anticancer drug candidate. PMID- 27203385 TI - Membranous CD24 drives the epithelial phenotype of pancreatic cancer. AB - Surface CD24 has previously been described, together with CD44 and ESA, for the characterization of putative cancer stem cells in pancreatic ductal adenocarcinoma (PDAC), the most fatal of all solid tumors. CD24 has a variety of biological functions including the regulation of invasiveness and cell proliferation, depending on the tumor entity and subcellular localization. Genetically engineered mouse models (GEMM) expressing oncogenic KrasG12D recapitulate the human disease and develop PDAC. In this study we investigate the function of CD24 using GEMM of endogenous PDAC and a model of cerulein-induced acute pancreatitis. We found that (i) CD24 expression was upregulated in murine and human PDAC and during acute pancreatitis (ii) CD24 was expressed exclusively in differentiated PDAC, whereas CD24 absence was associated with undifferentiated tumors and (iii) membranous CD24 expression determines tumor subpopulations with an epithelial phenotype in grafted models. In addition, we show that CD24 protein is stabilized in response to WNT activation and that overexpression of CD24 in pancreatic cancer cells upregulated beta-catenin expression augmenting an epithelial, non-metastatic signature. Our results support a positive feedback model according to which (i) WNT activation and subsequent beta-catenin dephosphorylation stabilize CD24 protein expression, and (ii) sustained CD24 expression upregulates beta-catenin expression. Eventually, membranous CD24 augments the epithelial phenotype of pancreatic tumors. Thus we link the WNT/beta catenin pathway with the regulation of CD24 in the context of PDAC differentiation. PMID- 27203386 TI - Phosphorylation of E-cadherin at threonine 790 by protein kinase Cdelta reduces beta-catenin binding and suppresses the function of E-cadherin. AB - Proper control of cell-cell adhesion is crucial for embryogenesis and tissue homeostasis. In this study, we show that protein kinase C (PKC)delta, a member of the novel PKC subfamily, localizes at cell-cell contacts of epithelial cells through its C2-like domain in an F-actin-dependent manner. Upon hepatocyte growth factor stimulation, PKCdelta is phosphorylated and activated by Src, which then phosphorylates E-cadherin at Thr790. Phosphorylation of E-cadherin at Thr790 diminishes its interaction with beta-catenin and impairs the homophilic interaction between the ectodomains of E-cadherin. The suppression of PKCdelta by its dominant-negative mutants or specific short-hairpin RNA inhibits the disruption of cell-cell adhesions induced by hepatocyte growth factor. Elevated PKCdelta expression in cancer cells is correlated with increased phosphorylation of E-cadherin at Thr790, reduced binding of E-cadherin to beta-catenin, and poor homophilic interaction between E-cadherin. Analysis of surgical specimens confirmed that PKCdelta is overexpressed in cervical cancer tissues, accompanied by increased phosphorylation of E-cadherin at Thr790. Together, our findings unveil a negative role for PKCdelta in cell-cell adhesion through phosphorylation of E-cadherin. PMID- 27203387 TI - Apigenin inhibits NF-kappaB and snail signaling, EMT and metastasis in human hepatocellular carcinoma. AB - Apigenin is a naturally occurring compound with anti-inflammatory, antioxidant, and anticancer properties. In this study, we investigated the effects of apigenin on migration and metastasis in experimental human hepatocellular carcinoma (HCC) cell lines in vitro and in vivo. Apigenin dose-dependently inhibited proliferation, migration, and invasion by PLC and Bel-7402 human HCC cells. It also suppressed tumor growth in PLC cell xenografts without altering body weight, thereby prolonging survival. Apigenin reduced Snai1 and NF-kappaB expression, reversed increases in epithelial-mesenchymal transition (EMT) marker levels, increased cellular adhesion, regulated actin polymerization and cell migration, and inhibited invasion and migration by HCC cells. Apigenin may therefore inhibit EMT by inhibiting the NF-kappaB/Snail pathway in human HCC. PMID- 27203388 TI - Identification and validation of AIB1 and EIF5A2 for noninvasive detection of bladder cancer in urine samples. AB - We previously demonstrated that amplified in breast cancer 1 (AIB1) and eukaryotic initiation factor 2 (EIF5A2) overexpression was an independent predictor of poor clinical outcomes for patients with bladder cancer (BCa). In this study, we evaluated the usefulness of AIB1 and EIF5A2 alone and in combination with nuclear matrix protein 22 (NMP22) as noninvasive diagnostic tests for BCa. Using urine samples from 135 patients (training set, controls [n = 50] and BCa [n = 85]), we detected the AIB1, EIF5A2, and NMP22 concentrations using enzyme-linked immunosorbent assay. We applied multivariate logistic regression analysis to build a model based on the three biomarkers for BCa diagnosis. The diagnostic accuracy of the three biomarkers and the model were assessed and compared by the area under the curve (AUC) of the receiver operating characteristic. We validated the diagnostic accuracy of these biomarkers and the model in an independent validation cohort of 210 patients. In the training set, urinary concentrations of AIB1, EIF5A2, and NMP22 were significantly elevated in BCa. The AUCs of AIB1, EIF5A2, NMP22, and the model were 0.846, 0.761, 0.794, and 0.919, respectively. The model had the highest diagnostic accuracy when compared with AIB1, EIF5A2, or NMP22 (p < 0.05 for all). The model had 92% sensitivity and 92% specificity. We obtained similar results in the independent validation cohort. AIB1 and EIF5A2 show promise for the noninvasive detection of BCa. The model based on AIB1, EIF5A2, and NMP22 outperformed each of the three individual biomarkers for detecting BCa. PMID- 27203389 TI - Inhibition of chronic lymphocytic leukemia progression by full-length chromogranin A and its N-terminal fragment in mouse models. AB - Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of leukemic B cells in peripheral blood, bone marrow (BM) and lymphoid tissues, and by their recirculation between these compartments. We observed that circulating chromogranin A (CgA) and its N-terminal fragment (called vasostatin-1, CgA1-76), two neuroendocrine secretory polypeptides that enhance the endothelial barrier function, are present in variable amounts in the blood of CLL patients. Studies in animal models showed that daily administration of full-length human CgA1-439 (0.3 MUg, i.v., or 1.5 MUg/mouse, i.p.) can reduce the BM/blood ratio of leukemic cells in EMU-TCL1 mice, a transgenic model, and decrease BM, lung and kidney infiltration in Rag2-/-gammac-/- mice engrafted with human MEC1 CLL cells, a xenograft model. This treatment also reduced the loss of body weight and improved animal motility. In vitro, CgA enhanced the endothelial barrier integrity and the trans-endothelial migration of MEC1 cells, with a bimodal dose-response curve. Vasostatin-1, but not a larger fragment consisting of N-terminal and central regions of CgA (CgA1-373), inhibited CLL progression in the xenograft model, suggesting that the C-terminal region is crucial for CgA activity and that the N terminal domain contains a site that is activated by proteolytic cleavage. These findings suggest that circulating full-length CgA and its fragments may contribute to regulate leukemic cell trafficking and reduce tissue infiltration in CLL. PMID- 27203390 TI - GLK/MAP4K3 overexpression associates with recurrence risk for non-small cell lung cancer. AB - Lung cancer is the leading cause of cancer death worldwide. Non-small cell lung cancer (NSCLC) accounts for 85% of total lung cancers; 40% to 60% of NSCLC patients die of cancer recurrence after cancer resection. Since GLK (also named MAP4K3) induces activation of NF-kappaB, which contributes to tumor progression, we investigated the role of GLK in NSCLC. GLK protein levels of 190 samples from pulmonary tissue arrays and 58 pulmonary resection samples from stage I to stage III NSCLC patients were studied using immunohistochemistry or immunoblotting. High levels of GLK proteins were detected in pulmonary tissues from NSCLC patients. Elevated GLK protein levels were correlated with increased recurrence risks and poor recurrence-free survival rates in NSCLC patients after adjusting for pathologic stage, smoking status, alcohol status, and EGFR levels. Thus, GLK is a novel prognostic biomarker for NSCLC recurrence. PMID- 27203392 TI - NEURL rs6584555 and CAND2 rs4642101 contribute to postoperative atrial fibrillation: a prospective study among Chinese population. AB - Postoperative atrial fibrillation (POAF) is a serious, common complication after coronary artery bypass grafting (CABG) surgery. Recently, 5 novel loci were identified to be associated with atrial fibrillation susceptibility using a combination of genotyping, eQTL mapping, and functional validation. In current study, we aim to evaluated the positive findings for POAF susceptibility after CABG among Chinese population, using a population-based, two-stage, nested case control study with 1,400 patients. NEURL rs12415501 and CAND2 rs4642101 were significantly associated with POAF susceptibility after CABG among Chinese population in both stages. When pooled together, the ORs for each additional copy of minor allele was 1.29 (95% CI: 1.13-1.48, P = 1.7*10-4) for NEURL rs12415501, and 1.21 (95% CI: 1.08-1.36, P = 9.8*10-4) for CAND2 rs4642101. Functional validation experiments found the AF risk allele of NEURL rs6584555 and CAND2 rs4642101 correlated with an increased expression of its corresponding genes (P<0.001). In this independently collected cardiac surgery cohort, we replicated the previous findings, and 2 novel loci are independently associated with POAF risk in patients who undergo CABG surgery in Chinese population. PMID- 27203391 TI - Sialic acid removal from dendritic cells improves antigen cross-presentation and boosts anti-tumor immune responses. AB - Dendritic cells (DCs) hold promise for anti-cancer immunotherapy. However, clinically, their efficiency is limited and novel strategies to improve DC mediated anti-tumor responses are needed. Human DCs display high content of sialic acids, which inhibits their maturation and co-stimulation capacity. Here, we aimed to understand whether exogenous desialylation of DCs improves their anti tumor immunity. Compared to fully sialylated DCs, desialylated human DCs loaded with tumor-antigens showed enhanced ability to induce autologous T cells to proliferate, to secrete Th1 cytokines, and to specifically induce tumor cell apoptosis. Desialylated DCs showed an increased expression of MHC-I and -II, co stimulatory molecules and an augmented secretion of IL-12. Desialylated HLA A*02:01 DCs pulsed with gp100 peptides displayed enhanced peptide presentation through MHC-I, resulting in higher activation ofgp100280-288 specific CD8+ cytotoxic T cells. Desialylated murine DCs also exhibited increased MHC and co stimulatory molecules and higher antigen cross-presentation via MHC-I. These DCs showed higher ability to activate antigen-specific CD4+ and CD8+ T cells, and to specifically induce tumor cell apoptosis. Collectively, our data demonstrates that desialylation improves DCs' ability to elicit T cell-mediated anti-tumor activity, due to increased MHC-I expression and higher antigen presentation via MHC-I. Sialidase treatment of DCs may represent a technology to improve the efficacy of antigen loaded-DC-based vaccines for anti-cancer immunotherapy. PMID- 27203394 TI - Ultrasound-Guided Interscalene Block: Reevaluation of the "Stoplight" Sign and Clinical Implications. AB - BACKGROUND AND OBJECTIVES: The "stoplight" sign is a frequently described image during ultrasound-guided interscalene block, referring to 3 hypoechoic structures found between the anterior and middle scalene muscles.This study was designed to establish the ultrasound-anatomy correlation of this sign and to find any other anatomical features within the roots that could help with the interpretation of the ultrasound images obtained at the interscalene level. METHODS: We performed 20 dissections of the brachial plexus in 10 embalmed human cadavers and systematically analyzed and measured the roots of C5 to C7 and then correlated these findings with ultrasonographic images on file. RESULTS: We found that the C5 root is significantly smaller than either C6 or C7 (P < 0.0001). We also found that C6 and C7, but not C5, frequently present macroscopic evidence of intraroot splitting visible to the naked eye. We also found that the roots of C5 and C6, but not of C7, present frequent variations in their relationship with the scalene muscles. CONCLUSIONS: Our results provide the anatomic basis to define the stoplight sign as one made of, from cephalad to caudal, the root of C5, the upper fascicle(s) of C6, and the lower fascicle(s) of C6 without contribution from C7. The important clinical implication is that an injection attempted between what is commonly perceived as the gap between C6 and C7 would indeed be an intraneural injection at C6, which could potentially spread toward the neuraxial space. PMID- 27203393 TI - PTRF suppresses the progression of colorectal cancers. AB - As a key component of caveolae structure on the plasma membrane, accumulated evidence has suggested that Polymerase I and Transcript Release Factor (PTRF) plays a pivotal role in suppressing the progression of human malignances. However, the function of PTRF in the development of colorectal cancers is still unclear. Here we report that the expression of PTRF is significantly reduced in tumor tissues derived from human patients with colorectal cancers, and that the downregulation of PTRF correlates to the advanced stage of the disease. In addition, we found that the expression of PTRF negatively regulates the tumorigenic activities of colorectal cell lines (Colo320, HT29 and CaCo2). Furthermore, ectopic PTRF expression caused significant suppression of cellular proliferation, and anchorage-independent colony growth of Colo320 cells, which have the lowest expression level of PTRF in the three studied cell lines. Meanwhile, shRNA mediated knockdown of PTRF in CaCo2 cells significantly promoted cellular proliferation and anchorage-independent colony growth. In addition, in vivo assays further revealed that tumor growth was significantly inhibited in xenografts with ectopic PTRF expression as compared to untreated Colo320 cells, but was markedly enhanced in PTRF knockdown CaCo2 cells. Biochemical studies revealed that overexpression of PTRF led to the suppression of the AKT/mTOR pathway, as evidenced by reduced phosphorylation of AKT, mTOR, and downstream MMP 9. Thus, these findings, for the first time, demonstrated that PTRF inhibits the tumorigenesis of colorectal cancers and that it might serve as a potential therapeutic target for human colon cancer patients. PMID- 27203395 TI - Bleeding Complications in Patients Undergoing Celiac Plexus Block. AB - BACKGROUND AND OBJECTIVES: Celiac plexus blockade has known risks including bleeding and neurologic injury because of the close proximity of vascular and neuraxial structures. The aim of this study was to determine the incidence of bleeding complications in patients undergoing celiac plexus block (CPB), with an emphasis on preprocedural antiplatelet medication use and coagulation status. METHODS: This is a retrospective study from 2005 to 2014 of adult patients undergoing CPB by the pain medicine division at a tertiary care center. The primary outcome was red blood cell (RBC) transfusion within 72 hours of needle placement, with a secondary outcome of bleeding complications requiring emergency medicine, neurology, or neurosurgical evaluation within 31 days. RESULTS: A total of 402 procedures were performed on 298 unique patients, with 58 patients (14.4%) receiving aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) preoperatively. Five patients (1.2%) received RBC transfusion within 72 hours, of which one had received preprocedure NSAIDs. A platelet count measured within 30 days was available for 268 patients, with 7 patients (2.6%) having platelet counts of 100 * 10/L or less at the time of needle placement. A total of 187 patients had a valid preoperative international normalized ratio (INR), with 9 (4.8%) having an INR of 1.5 or higher (range, 1.5-2.6). One patient (11.1%) required RBC transfusion compared with an RBC transfusion rate of 2.3% (4 of 178) in those with normal INR (P = 0.221). We identified no bleeding complications requiring emergency medicine, neurology, or neurosurgical evaluation. CONCLUSIONS: This study suggests that CPBs may be safely performed in patients receiving aspirin and/or NSAID therapy. PMID- 27203396 TI - Regional Anesthesia Is Cost-Effective in Preventing Unanticipated Hospital Admission in Pediatric Patients Having Anterior Cruciate Ligament Reconstruction. AB - BACKGROUND AND OBJECTIVES: Published studies have shown a benefit of regional anesthesia (RA) in preventing unplanned hospital admissions (UHAs) and decreasing hospital costs after orthopedic surgeries in adults but not pediatric patients. We performed a retrospective analysis to assess the effect of converting from an opioid to RA-based approach to pain management after pediatric anterior cruciate ligament (ACL) reconstruction. METHODS: The records of patients having ACL reconstruction were reviewed. Two groups, those with (n = 115) and without (n = 39) nerve blocks, were identified. Single-shot blocks or indwelling catheters were performed in the operating room (OR) or a block room. Time to discharge readiness, postoperative opiate and antiemetic consumption, hospital admission or discharge, and complications were recorded. The cost of providing RA, the change in UHA and postanesthesia care unit utilization, and subsequent financial impact were calculated. RESULTS: Regional anesthesia-based pain management was associated with a lower rate of UHA (P = 0.045), less time in postanesthesia care unit phase II (P = 0.013), and a reduction in opioid consumption (P < 0.001). Use of a dedicated RA team with a dedicated block room resulted in cost savings or neutrality, whereas RA catheters placed in the OR were associated with increased direct hospital costs. CONCLUSIONS: Regional anesthesia for pain after ACL repair in pediatric patients facilitated reliable same-day surgery discharge and significantly reduced UHAs. Single-shot blocks and blocks performed outside the OR were the most cost-effective. In addition, nerve block patients required less opioids and were ready for discharge sooner. PMID- 27203397 TI - CD13 Autoantibodies Are Elevated in Sera From Mothers of Infants With Neonatal Cholestasis of Different Causes. AB - OBJECTIVES: Human cytomegalovirus (HCMV) infection induces production of CD13 specific autoantibodies, which may promote inflammation and tissue damage. HCMV infection has been suggested as a cause of biliary atresia (BA), but little is known of its role in other forms of neonatal cholestasis. We studied serum levels of CD13-specific autoantibodies in mothers of infants with neonatal cholestasis of different causes, including BA, and in mothers of healthy, term infants without cholestasis, as well as in healthy blood donors. METHODS: Using fluorescence-activated cell sorting, we measured CD13-specific autoantibody levels in serum from the above-mentioned groups. In addition, the effect of serum from mothers of infants with neonatal cholestasis was tested on the differentiation of monocytes into macrophages. RESULTS: CD13-specific autoantibodies were found in mothers of infants with neonatal cholestasis, but not in mothers of infants without cholestasis and healthy blood donors, and were associated with HCMV seropositivity. Sera from mothers of infants with all forms of neonatal cholestasis inhibited differentiation of monocytes into macrophages, but this was not dependent on CD13-specific autoantibodies. CONCLUSIONS: The significantly higher frequency of CD13-specific autoantibodies in mothers of infants with neonatal cholestasis of all forms compared with mothers of healthy infants without cholestasis suggests an association, but does not prove that they are pathogenic. The presence of CD13-specific autoantibodies does not correlate with HCMV IgG serostatus, suggesting a more complicated mechanism that possibly reflects active HCMV infection in these individuals. Further studies are needed to elucidate whether these autoantibodies contribute to the development of cholestasis or represent an epiphenomenon. PMID- 27203398 TI - Cumulative Risk Impact of RET, SEMA3, and NRG1 Polymorphisms Associated With Hirschsprung Disease in Han Chinese. AB - OBJECTIVES: Hirschsprung disease (HSCR) is a congenital aganglionosis of myenteric and submucosal plexuses affecting a variable length of the intestine. The incidence of HSCR is approximately 1 of 5000 live births; however, the risk shows remarkable individual variation caused by single nucleotide polymorphisms (SNPs) at the RET, SEMA3, and NRG1 loci. The present study investigated the effects of these variants on the disease development and phenotype in a Chinese population. METHODS: In total, 6 SNPs were genotyped in a cohort consisting of 115 patients with HSCR and 117 unaffected controls using a TaqMan genotyping assay. Histological identification of the affected-segment length (short, long, or total colonic aganglionosis) was performed for all of the samples before DNA extraction. RESULTS: Significant genetic risk was imparted by rs2435357 and rs2506030 at RET and by rs12707682 at SEMA3. In addition, the average cumulative risk score in the patients with HSCR was significantly higher than that in the controls. Through the assessment of risk alleles by effect size, individuals were classified into 3 weighted risk score groups: low (<=3), medium (4), and high (>=5). Individuals in the high group were significantly more susceptible to HSCR than those in the low group with an odds ratio of 7.7 (95% confidence interval 3.7-16.3). CONCLUSIONS: Cumulative genetic risk varied >35-fold between newborns with zero and >5 accumulated susceptibility alleles. The SNPs rs2435357, rs2506030, and rs12707682 may be useful for stratifying the Chinese population into distinct risk groups. PMID- 27203399 TI - Tunable Ferromagnetic Transition Temperature and Vertical Hysteretic Shift in SrRuO3 Films Integrated on Si(001). AB - SrRuO3 thin films have been epitaxially integrated on complementary metal oxide semiconductor (CMOS) compatible Si(001) substrates via pulsed laser deposition using a unique buffer layer (SrTiO3/TiN) approach. When the oxygen pressure during deposition was controlled, a dramatic suppression in the ferromagnetic transition temperature (TC) of up to 53 K was observed, caused by the growth induced ruthenium vacancies rather than the oxygen vacancies. The ruthenium vacancies can also effectively tune the vertical magnetization shift (Mshift) in hysteresis loops, and thus we achieved a giant Mshift of 240%. Transport and magnetic measurements reveal that these appreciable physical phenomena are closely related to the ruthenium defect-induced local disorder and complex effects due to the strongly hybridized p-d orbitals as well as the induced lattice distortion. These observations indicate the importance of ruthenium defects in controlling the vertical magnetization shift and ferromagnetic transition temperature in this transitional metal oxide. PMID- 27203400 TI - An epidemiological study to assess the true incidence and prevalence of rheumatic heart disease and acute rheumatic fever in New Caledonian school children. AB - AIM: To provide in New Caledonian school children (i) the prevalence of rheumatic heart disease (RHD) detected by annual screening program using new World Heart Federation diagnostic criteria; (ii) the point prevalence of acute rheumatic fever (ARF); and (iii) to investigate socio-demographic risk factors associated with RHD. METHODS: This study linked data from national ARF/RHD programs by combining ARF incidence data from the register with RHD prevalence data from echocardiographic screening data for a single age year of the population for overall point prevalence ARF/RHD rates. For the analysis, cases of echocardiographic detection of RHD are presumed to be synonymous with undiagnosed ARF. All results were weighted to minimise the bias introduced from absent pupils of each annual screening program. Incidence and prevalence were age-standardised to the WHO World Standard Population. Each 2013 cumulative prevalence of definite and borderline RHD was studied using a multivariate logistic regression adjusted for socio-demographic factors. RESULTS: The overall age-standardised incidence of clinical and undiagnosed ARF (i.e. echocardiographic-detected RHD) was combined as point prevalence and estimated to be 99/10 000 cases in 2012 and 114/10 000 cases in 2013. This included 40/10 000 prevalent cases of asymptomatic RHD detected by screening each year. Being Melanesian, OR 23.2 (95% CI: 3.4-157.3), or Polynesian, OR 21.5 (95% CI: 2.9-157.7), was associated with a higher prevalence of having definite RHD compared with being Caucasian. Being a girl was associated with a higher risk of having borderline RHD, OR 1.9 (95% CI: 1.03 3.3). CONCLUSION: Without echocardiographic screening, ARF/RHD burden is substantially underestimated. PMID- 27203401 TI - Reducing SAR requirements in multislice volumetric single-shot spatiotemporal MRI by two-dimensional RF pulses. AB - PURPOSE: Spatiotemporal encoding (SPEN) can deliver single-scan MR images without folding complications and with increased robustness to chemical shift and susceptibility artifacts. Yet, it does so at the expense of relatively high specific absorption rates (SAR) owing to its reliance on frequency-swept pulses. This study describes SPEN implementations aimed at full three-dimensional (3D) multislice imaging, possessing reduced SAR thanks to an implementation based on new 2D radiofrequency (RF) pulses. METHODS: Fully refocused spin- and stimulated echo SPEN sequences incorporating 2D spatial/spatial swept RF pulses were implemented at 3 Tesla and compared to echo planar imaging. The use of effective 90-degree slice-selective excitation pulses enabled the scanning of 3D volumes with a low SAR. RESULTS: Experiments validating the theoretical expectations were carried out on phantoms and on human volunteers, including zooming and diffusion measurements. The chosen sequences showed much smaller SARs than EPI, while delivering similar sensitivities when targeting human brain and fewer distortions when targeting human breast. CONCLUSION: Two-dimensional RF pulses can exploit SPEN's advantages while fulfilling the SAR and multislice coverage demands required for clinical imaging. Magn Reson Med 77:1959-1965, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 27203402 TI - Complementary and integrative medicine for breast cancer patients - Evidence based practical recommendations. AB - On average half of the breast cancer patients' population uses complementary and integrative medicine (CIM) therapies and many of them would like to receive information on CIM from their conventional treatment team. However, often they don't feel comfortable in discussing CIM related questions, with their conventional treatment team, because they think they don't have enough expertise and available time to deal with this topic. Furthermore, information on the evidence of CIM is not easily accessible and the available information is not always reliable. The purpose of the current paper is to provide: 1) an overview about the CIM interventions that have shown positive effects in breast cancer patients and might be useful in supportive cancer care, 2) practical guidance on how to choose and find a qualified referral to a CIM treatment: 3) recommendations on how these interventions could be integrated into Breast Cancer Centers and which factors should be taken into consideration in this setting. This paper takes available CIM practice guidelines for cancer patients and previous research on CIM implementation models into account. There are CIM interventions that have shown a potential to reduce symptoms of cancer or cancer treatments in breast cancer patients and the vast majority uses a non pharmacological approach and have a good potential for implementation. Nevertheless, further and more rigorous research is still needed. PMID- 27203403 TI - Modal Coupling of Single Photon Emitters Within Nanofiber Waveguides. AB - Nanoscale generation of individual photons in confined geometries is an exciting research field aiming at exploiting localized electromagnetic fields for light manipulation. One of the outstanding challenges of photonic systems combining emitters with nanostructured media is the selective channelling of photons emitted by embedded sources into specific optical modes and their transport at distant locations in integrated systems. Here, we show that soft-matter nanofibers, electrospun with embedded emitters, combine subwavelength field localization and large broadband near-field coupling with low propagation losses. By momentum spectroscopy, we quantify the modal coupling efficiency identifying the regime of single-mode coupling. These nanofibers do not rely on resonant interactions, making them ideal for room-temperature operation, and offer a scalable platform for future quantum information technology. PMID- 27203404 TI - Design, synthesis and biological evaluation of novel quinoline-based carboxylic hydrazides as anti-tubercular agents. AB - In this study, seventeen novel quinoline-based carboxylic hydrazides were designed as potential anti-tubercular agents using molecular hybridization approach and evaluated in-silico for drug-likeness behavior. The compounds were synthesized, purified, and characterized using spectral techniques (like FTIR, (1) H NMR, and Mass). The in-vitro anti-tubercular activity (against Mycobacterium tuberculosisH37Ra) and cytotoxicity against human lung fibroblast cells were studied. Among the tested hydrazides, four compounds (6h, 6j, 6l, and 6m) exhibited significant anti-tubercular activity with MIC values below 20 MUg/mL. The two most potent compounds of the series, 6j and 6m exhibited MIC values 7.70 and 7.13 MUg/mL, respectively, against M. tuberculosis with selectivity index >26. Structure-activity relationship studies were performed for the tested compounds in order to explore the effect of substitution pattern on the anti-tubercular activity of the synthesized compounds. PMID- 27203406 TI - The author file: Hana El-Samad. PMID- 27203407 TI - Use of Protein Cross-Linking and Radiolytic Labeling To Elucidate the Structure of PsbO within Higher-Plant Photosystem II. AB - We have used protein cross-linking with the zero-length cross-linker 1-ethyl-3-(3 dimethylaminopropyl) carbodiimide, and radiolytic footprinting coupled with high resolution tandem mass spectrometry, to examine the structure of higher-plant PsbO when it is bound to Photosystem II. Twenty intramolecular cross-linked residue pairs were identified. On the basis of this cross-linking data, spinach PsbO was modeled using the Thermosynechococcus vulcanus PsbO structure as a template, with the cross-linking distance constraints incorporated using the MODELLER program. Our model of higher-plant PsbO identifies several differences between the spinach and cyanobacterial proteins. The N-terminal region is particularly interesting, as this region has been suggested to be important for oxygen evolution and for the specific binding of PsbO to Photosystem II. Additionally, using radiolytic mapping, we have identified regions on spinach PsbO that are shielded from the bulk solvent. These domains may represent regions on PsbO that interact with other components, as yet unidentified, of the photosystem. PMID- 27203405 TI - Double epigenetic modulation of high-dose chemotherapy with azacitidine and vorinostat for patients with refractory or poor-risk relapsed lymphoma. AB - BACKGROUND: More active high-dose chemotherapy (HDC) regimens are needed for refractory lymphomas. The authors previously combined infusional gemcitabine with busulfan and melphalan (Gem/Bu/Mel) pursuing DNA damage repair inhibition. Subsequently, they combined Gem/Bu/Mel with vorinostat, which facilitates chemotherapy access to DNA. The resulting regimen was safe and synergistic. However, vorinostat induced DNA methyltransferase up-regulation, which could be preclinically abrogated by azacitidine, increasing tumor-cell kill. Those observations led to a clinical combination of azacitidine with vorinostat/Gem/Bu/Mel. METHODS: Patients ages 12 to 65 years with refractory or poor-risk relapsed lymphomas were eligible. They received intravenous azacitidine on days -11 through -3 at doses from 15 to 35 mg/m(2) daily (dose levels 1-3), followed by oral vorinostat (1000 mg once daily on days -11 through -3), gemcitabine (2775 mg/m(2) over 4.5 * 2), busulfan (at an area under the receiver operating characteristic curve of 4000 daily * 4), and melphalan (60 mg/m(2) * 2). Patients who had tumors that were positive for CD20 (cluster of differentiation 20; B-lymphocyte antigen) received rituximab on day -9. RESULTS: In total, 60 patients were enrolled, including 26 with diffuse large B-cell lymphoma (DLBCL) (10 double hit/double expressors), 21 with Hodgkin lymphoma, 8 with T-cell lymphoma, and 5 with other B-cell lymphomas. The median patient age was 41 years (range, 16-65 years), patients had received a median of 3 prior lines of chemotherapy (range, 2-7 lines of chemotherapy); and 32% of tumors were positive on positron emission tomography studies at the time of HDC. Two patients died from treatment complications (respiratory syncytial virus pneumonia and sepsis, respectively). The maximum tolerated dose of azacitidine was encountered at dose level 1 (15 mg/m(2) daily). The toxicity profile (mainly mucositis and dermatitis) was manageable and was identical to that of vorinostat/Gem/Bu/Mel. Neutrophils and platelets engrafted promptly. At a median follow-up of 15 months (range, 8-27 months), the event-free and overall survival rates were 65% and 77%, respectively, among patients with DLBCL; 76% and 95%, respectively, among patients with Hodgkin lymphoma; and 88% for both among patients with T-cell lymphoma. CONCLUSIONS: Double epigenetic modulation of Gem/Bu/Mel with azacitidine/vorinostat is feasible and highly active in patients with refractory/poor-risk relapsed lymphomas, warranting further evaluation. Cancer 2016. (c) 2016 American Cancer Society. Cancer 2016;122:2680-2688. (c) 2016 American Cancer Society. PMID- 27203408 TI - Fatigue analysis of computer-aided design/computer-aided manufacturing resin based composite vs. lithium disilicate glass-ceramic. AB - Resin-based composite molar crowns made by computer-aided design/computer-aided manufacturing (CAD/CAM) systems have been proposed as an inexpensive alternative to metal-ceramic or all-ceramic crowns. However, there is a lack of scientific information regarding fatigue resistance. This study aimed to analyze the fatigue behavior of CAD/CAM resin-based composite compared with lithium disilicate glass ceramic. One-hundred and sixty bar-shaped specimens were fabricated using resin based composite blocks [Lava Ultimate (LU); 3M/ESPE] and lithium disilicate glass ceramic [IPS e.max press (EMP); Ivoclar/Vivadent]. The specimens were divided into four groups: no treatment (NT); thermal cycling (TC); mechanical cycling (MC); and thermal cycling followed by mechanical cycling (TCMC). Thermal cycling was performed by alternate immersion in water baths of 5 degrees C and 55 degrees C for 5 * 10(4) cycles. Mechanical cycling was performed in a three-point bending test, with a maximum load of 40 N, for 1.2 * 10(6) cycles. In addition, LU and EMP molar crowns were fabricated and subjected to fatigue treatments followed by load-to-failure testing. The flexural strength of LU was not severely reduced by the fatigue treatments. The fatigue treatments did not significantly affect the fracture resistance of LU molar crowns. The results demonstrate the potential of clinical application of CAD/CAM-generated resin-based composite molar crowns in terms of fatigue resistance. PMID- 27203409 TI - Trends in the Epidemiology of Campylobacteriosis in Israel (1999-2012). AB - The objective of this study was to examine the recent trends in the epidemiology of campylobacteriosis in Israel. A Sentinel Laboratory-Based Surveillance Network for Bacterial Enteric Diseases was established in Israel by the Israel Center for Disease Control (ICDC). This network generated data on subjects from whom Campylobacter spp. was isolated in community and hospital laboratories. Further characterization of the isolates was done at the Campylobacter National Reference Laboratory. Data from these two sources were integrated and analyzed at the ICDC. Between 1999 and 2012, 40,978 Campylobacter stool isolates were reported to the ICDC by the sentinel laboratories. The incidence rate of campylobacteriosis increased from 65.7 per 100,000 in 1999 to 101.7 per 100,000 in 2012. This increase resulted from a significant rise in the incidence of campylobacteriosis in the Jewish population which, since 2009, surpassed the consistent higher incidence of the disease in Israeli Arabs. The peak morbidity in Israel consistently occurred in late spring, with a risk excess in males compared with females, in younger age groups and earlier in the life span among Arabs than among Jews and others. These results suggest that further analytical studies should be carried out to identify risk factors responsible for the increased incidence of campylobacteriosis and better direct prevention and control of the disease in Israel. PMID- 27203410 TI - Usefulness of Serum Calcitonin in Patients Without a Suspicious History of Medullary Thyroid Carcinoma and with Thyroid Nodules Without an Indication for Fine-Needle Aspiration or with Benign Cytology. AB - This study evaluated the usefulness of serum calcitonin (Ctn) in subjects without a suspicious history of medullary thyroid carcinoma (MTC) and with nodular thyroid disease without an indication for fine-needle aspiration (FNA) or with benign cytology. This was a prospective study that evaluated 421 patients with nodular disease without an indication for FNA and 602 patients with benign cytology. Patients with basal Ctn>10 pg/ml were submitted to calcium stimulation testing. Patients with stimulated Ctn>100 pg/ml were submitted to total thyroidectomy. Basal Ctn was<10 pg/ml in 1001 patients (97.8%). Among patients with basal Ctn>10 pg/ml, 16/22 exhibited stimulated Ctn>100 pg/ml. Two of these 16 patients had MTC. The 2 patients with MTC had undetectable basal Ctn 6 months after surgery. Using a cut-off of 30 pg/ml in women and 60 pg/ml in men for basal Ctn, the 2 cases of MTC of our series would have been identified and there would have been no false-positive case. It should be noted that 14/16 patients with stimulated Ctn>100 pg/ml were false-positive cases. Although uncommon, even subjects without a suspicious history and with nodular thyroid disease without an indication for FNA or with benign cytology can have MTC. The measurement of Ctn permits the diagnosis of these cases. Our results favor the hypothesis that basal Ctn could be superior to stimulated Ctn. PMID- 27203411 TI - Gut Microbiota as a Target in the Pathogenesis of Metabolic Disorders: A New Approach to Novel Therapeutic Agents. AB - As the prevalence of metabolic disorders increases dramatically, the importance of identifying environmental factors affecting metabolism control becomes greater accordingly. Gut microbiota, a complex ecosystem inhabiting the human gastrointestinal tract, is one of these potential factors. Recently, the evidence has shown the associations between alteration in gut microbiota composition and obesity, diabetes, and osteoporosis. However, the causality of gut microbiota on metabolic health has yet to be explored in intervention studies and the underlying mechanisms need to be investigated more in depth. Gut microbiota plays critical roles in the control of immunity, food intake, lipid accumulation, production of short chain fatty acids, insulin signaling, and regulation of bone mass. The gut microbiota represents a novel potential therapeutic strategy for the treatment of metabolic disorders. In this review, we provide insights into the role of the gut microbiota in metabolic disorders and its modulating interventions such as prebiotics, probiotics, and fecal microbiota transplantation. PMID- 27203412 TI - Knee Bracing After Anterior Cruciate Ligament Reconstruction. AB - Although some articles in the literature are in favor of the use of a postoperative brace after anterior cruciate ligament (ACL) reconstruction, this review found that several systematic reviews and other reports on the topic do not support the use of a postoperative brace after ACL reconstruction. There is no scientific evidence so far to support the routine use of a functional knee brace following a successful ACL reconstruction in the postoperative course. Most authors believe that bracing is not necessary. There is insufficient evidence to inform current practice. Good-quality randomized trials are required to remedy this situation. Future studies should better define the role of a brace following ACL surgery. A search of MEDLINE for articles published between January 1, 1995, and September 30, 2013, was performed. Key search terms used were ACL reconstruction and knee brace. Ninety-one articles were found, but only 28 focused on the subject of bracing after ACL reconstruction and were selected for this review. Several systematic reviews and randomized, controlled trials on the topic do not recommend the use of postoperative brace after ACL reconstruction. Postoperative bracing after ACL reconstruction does not seem to help with pain, function, rehabilitation, and stability. The literature does not support the use of a postoperative brace following ACL reconstruction. [Orthopedics. 2016; 39(4):e602-e609.]. PMID- 27203413 TI - Double-Level Pelvic Osteotomy for Managing Persistent Acetabular Dysplasia. AB - Pemberton's osteotomy has been recognized as a standard technique for the treatment of acetabular dysplasia. The aim of this article is to describe the surgical technique of a double-level pelvic osteotomy. To the authors' knowledge, this technique has never been reported. The osteotomy was performed in a case of severe pan-acetabular dysplasia where a single, classic Pemberton's osteotomy was not sufficient to provide adequate coverage. The described osteotomy provided sufficient acetabular coverage and overcame the persistent acetabular dysplasia. [Orthopedics. 2016; 39(4):e806-e809.]. PMID- 27203414 TI - Characteristics and Complications of Super-Obese Patients Who Underwent Total Knee Arthroplasty. AB - Preoperative demographic characteristics, comorbidities, length of stay and surgery, and postoperative complications were compared between super-obese (n=1042) and nonobese (n=19,929) patients who underwent total knee arthroplasty. Super-obese patients were younger, were predominantly women, had an increased incidence of comorbid conditions such as diabetes and hypertension as well as a high rate of superficial and deep wound infections, and had a longer mean length of stay and operative time. Although super-obese patients have unique demographic characteristics and increased postoperative complications and length of stay, they may still benefit from total knee arthroplasty. Surgeons should note their high incidence of infections. [Orthopedics. 2016; 39(4):e800-e805.]. PMID- 27203415 TI - Same-Level Fracture of the Tibial Metal Tray and Polyethylene Insert After Total Knee Arthroplasty. AB - The authors report a case of failure fracture of the tibial metal tray and polyethylene insert at the same level in a 73-year-old woman 10 years after total knee arthroplasty using the AMK Total Knee System (DePuy, Warsaw, Indiana). Causes of this fracture are analyzed and discussed, with the focus on the importance of component design, position, and size. The overall aim of this case report is for orthopedic surgeons to avoid this complication in total knee arthroplasty by paying attention to these controllable factors. [Orthopedics. 2016; 39(4):e787-e789.]. PMID- 27203416 TI - Knee Disarticulation for a Total Knee Arthroplasty Periprosthetic Fracture. AB - Total knee arthroplasty, although a very successful surgery, can present the patient with several potential complications, including the risk for periprosthetic fractures. Complications involving periprosthetic fractures after total knee arthroplasty can present a complex clinical scenario for orthopedic surgeons. To date, adequate literature exists to guide surgeons in approaching most periprosthetic fractures; however, standard operating procedure can fall short when confronted with more complex clinical scenarios. The authors present an alternative approach, falling outside the traditional paradigm, to addressing a periprosthetic tibial fracture in the setting of a previous total knee arthroplasty. Given both the patient's physiological factors and the inherent factors of the fracture, the authors found that the first-line treatments for periprosthetic fracture, including open reduction and internal fixation and joint revision, were inadequate and posed more potential risks than benefits for the patient. In light of this situation, the authors elected to treat this patient's periprosthetic fracture with a through knee amputation, as this provided the patient with the lowest cost in morbidity while still addressing the fracture. [Orthopedics. 2016; 39(4):e775-e778.]. PMID- 27203417 TI - Failure of a Unipolar Radial Head Prosthesis Due to Component Dissociation. AB - Radial head implant arthroplasty is a consideration for the treatment of comminuted, unreconstructable fractures of the radial head. Many prosthetic designs exist and can be unipolar or bipolar, each of which can be cemented or noncemented. For most unipolar designs, a prosthetic stem is first implanted into the proximal radius. The prosthetic radial head is then impacted onto a morse taper on the stem or secured with a set screw. There is little information published on the mechanisms of failure for radial head implants, regardless of design. The authors found 2 individual case reports that describe component dissociation in bipolar implants. They could find no individual case reports of implant failure due to component dissociation of a unipolar implant related to failure of the set screw. The authors describe such a case 5 years after unipolar radial head implant arthroplasty. The system used employs a set screw to secure the prosthetic head onto the stem. The patient subsequently had a successful outcome after implant removal without reimplantation. Orthopedic surgeons have many options when considering radial head replacement implants and should be aware of the potential complications of each. The authors present this case to show one potential complication of unipolar prosthetic radial head implant arthroplasty. [Orthopedics. 2016; 39(4):e771-e774.]. PMID- 27203418 TI - Nanoengineered Templated Polymer Particles: Navigating the Biological Realm. AB - Nanoengineered materials offer tremendous promise for developing the next generation of therapeutics. We are transitioning from simple research questions, such as "can this particle eradicate cancer cells?" to more sophisticated ones like "can we design a particle to preferentially deliver cargo to a specific cancer cell type?" These developments are poised to usher in a new era of nanoengineered drug delivery systems. We primarily work with templating methods for engineering polymer particles and investigate their biological interactions. Templates are scaffolds that facilitate the formation of particles with well controlled size, shape, structure, stiffness, stability, and surface chemistry. In the past decade, breakthroughs in engineering new templates, combined with advances in coating techniques, including layer-by-layer (LbL) assembly, surface polymerization, and metal-phenolic network (MPN) coordination chemistry, have enabled particles with specific physicochemical properties to be engineered. While materials science offers an ever-growing number of new synthesis techniques, a central challenge of therapeutic delivery has become understanding how nanoengineered materials interact with biological systems. Increased collaboration between chemists, biologists, and clinicians has resulted in a vast research output on bio-nano interactions. Our understanding of cell-particle interactions has grown considerably, but conventional in vitro experimentation provides limited information, and understanding how to bridge the in vitro/in vivo gap is a continuing challenge. As has been demonstrated in other fields, there is now a growing interest in applying computational approaches to advance this area. A considerable knowledge base is now emerging, and with it comes new and exciting opportunities that are already being capitalized on through the translation of materials into the clinic. In this Account, we outline our perspectives gained from a decade of work at the interface between polymer particle engineering and bio-nano interactions. We divide our research into three areas: (i) biotrafficking, including cellular association, intracellular transport, and biodistribution; (ii) biodegradation and how to achieve controlled, responsive release of therapeutics; and (iii) applications, including drug delivery, controlling immunostimulatory responses, biosensing, and microreactors. There are common challenges in these areas for groups developing nanoengineered therapeutics. A key "lesson-learned" has been the considerable challenge of staying informed about the developments relevant to this field. There are a number of reasons for this, most notably the interdisciplinary nature of the work, the large numbers of researchers and research outputs, and the limited standardization in technique nomenclature. Additionally, a large body of work is being generated with limited central archiving, other than vast general databases. To help address these points, we have created a web-based tool to organize our past, present, and future work [Bio-nano research knowledgebase, http://bionano.eng.unimelb.edu.au/knowledge_base/ (accessed May 2, 2016)]. This tool is intended to serve as a first step toward organizing results in this large, complex area. We hope that this will inspire researchers, both in generating new ideas and also in collecting, collating, and sharing their experiences to guide future research. PMID- 27203419 TI - Hippocampal Neurometabolite Changes in Hypothyroidism: An In Vivo (1) H Magnetic Resonance Spectroscopy Study Before and After Thyroxine Treatment. AB - The hippocampus is a thyroid hormone receptor-rich region of the brain. A change in thyroid hormone levels may be responsible for an alteration in hippocampal associated function, such as learning, memory and attention. Neuroimaging studies have shown functional and structural changes in the hippocampus as a result of hypothyroidism. However, the underlying process responsible for this dysfunction remains unclear. Therefore, the present study aimed to investigate the metabolic changes in the brain of adult hypothyroid patients during pre- and post-thyroxine treatment using in vivo proton magnetic resonance spectroscopy ((1) H MRS). (1) H MRS was performed in both healthy control subjects (n = 15) and hypothyroid patients (n = 15) (before and after thyroxine treatment). The relative ratios of the neurometabolites were calculated using the linear combination model (LCModel). Our results revealed a significant decrease of glutamate (Glu) (P = 0.045) and myo-inositol (mI) (P = 0.002) levels in the hippocampus of hypothyroid patients compared to controls. No significant changes in metabolite ratios were observed in the hypothyroid patients after thyroxine treatment. The findings of the present study reveal decreased Glu/tCr and mI/tCr ratios in the hippocampus of hypothyroid patients and these metabolite alterations persisted even after the patients became clinically euthyroid subsequent to thyroxine treatment. PMID- 27203420 TI - Microvasculature of the California sea lion (Zalophus californianus) eye and its functional significance. AB - OBJECTIVE: To examine the ocular circulation in California sea lions (Zalophus californianus). ANIMALS STUDIED: Eyes were obtained postmortem from three sea lions that died while in captivity. PROCEDURES: Specimens from sea lions were investigated using scanning electron microscopy (SEM) of vascular corrosion casts. The thermal characteristics of live animal eyes were measured using an infrared imaging system. RESULTS: The major orbital artery of the sea lion was the ophthalmic artery. The artery was remarkably thick in diameter, showed a marked convolution and formed an ophthalmic rete around the optic nerve at the posterior pole of the eyeball. The long posterior ciliary artery terminates to form a prominent inner arterial circle at the pupillary margin. The iridial arteries originated from the arterial circle showing either a crimped or somewhat coiled course, extending toward the root of the iris and formed a root supplying a large amount of blood to the iris and ciliary bodies. The venules in the conjunctiva formed a well-developed venous plexus. The vortex veins showed a dilation and constriction at the site passing through the sclera. Thermographic examination revealed that the eye showed a higher degree of thermal emission than adjacent skin areas. CONCLUSIONS: These characteristics suggest that the ocular vasculature might play roles in thermoregulation as well as in hemodynamics by draining a large amount of blood so that the appropriate operating temperature for the eye can be maintained in a deep and cold aquatic environment. PMID- 27203421 TI - Biophysical Network Modelling of the dLGN Circuit: Different Effects of Triadic and Axonal Inhibition on Visual Responses of Relay Cells. AB - Despite its prominent placement between the retina and primary visual cortex in the early visual pathway, the role of the dorsal lateral geniculate nucleus (dLGN) in molding and regulating the visual signals entering the brain is still poorly understood. A striking feature of the dLGN circuit is that relay cells (RCs) and interneurons (INs) form so-called triadic synapses, where an IN dendritic terminal can be simultaneously postsynaptic to a retinal ganglion cell (GC) input and presynaptic to an RC dendrite, allowing for so-called triadic inhibition. Taking advantage of a recently developed biophysically detailed multicompartmental model for an IN, we here investigate putative effects of these different inhibitory actions of INs, i.e., triadic inhibition and standard axonal inhibition, on the response properties of RCs. We compute and investigate so called area-response curves, that is, trial-averaged visual spike responses vs. spot size, for circular flashing spots in a network of RCs and INs. The model parameters are grossly tuned to give results in qualitative accordance with previous in vivo data of responses to such stimuli for cat GCs and RCs. We particularly investigate how the model ingredients affect salient response properties such as the receptive-field center size of RCs and INs, maximal responses and center-surround antagonisms. For example, while triadic inhibition not involving firing of IN action potentials was found to provide only a non linear gain control of the conversion of input spikes to output spikes by RCs, axonal inhibition was in contrast found to substantially affect the receptive field center size: the larger the inhibition, the more the RC center size shrinks compared to the GC providing the feedforward excitation. Thus, a possible role of the different inhibitory actions from INs to RCs in the dLGN circuit is to provide separate mechanisms for overall gain control (direct triadic inhibition) and regulation of spatial resolution (axonal inhibition) of visual signals sent to cortex. PMID- 27203422 TI - Canine Fibroblast Growth Factor 21 Ameliorates Hyperglycemia Associated with Inhibiting Hepatic Gluconeogenesis and Improving Pancreatic Beta-Cell Survival in Diabetic Mice and Dogs. AB - Diabetes mellitus is a common endocrinopathy in dog. Fibroblast growth factor 21 (FGF-21) is a secreted protein, which is involved in glucose homeostasis. We speculate that the recombinant canine FGF-21 (cFGF-21) has the potential to become a powerful therapeutics to treat canine diabetes. The cFGF-21 gene was cloned and expressed in E. coli Rosetta (DE3). After purification, a cFGF-21 protein with the purity exceeding 95% was obtained. Mouse 3T3-L1 adipocytes and type 1 diabetic mice/dogs induced by STZ were used to examine the biological activity of cFGF-21 in vitro and in vivo, respectively. Results showed that cFGF 21 stimulated glucose uptake in adipocytes significantly in a dose-dependent manner, and reduced plasma glucose significantly in diabetic mice/dogs. After treatment with cFGF-21, the serum insulin level, glycosylated hemoglobin (HbA1c) level and the expressions of the hepatic gluconeogenesis genes (glucose-6 phosphatase, G6Pase and phosphoenolpyruvate carboxykinase, PCK) of the diabetic mice/dogs were attenuated significantly. In the mouse experiment, we also found that the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and the expression of suppressor of cytokine signaling 3 (SOCS3) were up regulated significantly in the livers after treatment. Histopathological and immunohistochemical results showed that treatment with cFGF-21 promoted recovery of pancreatic islets from STZ-induced apoptosis. Besides, we also found that treatment with cFGF-21 protected liver against STZ or hyperglycemia induced damage and the mechanism of this action associated with inhibiting oxidative stress. In conclusion, cFGF-21 represents a promising candidate for canine diabetes therapeutics. The mechanism of cFGF-21 ameliorates hyperglycemia associated with inhibiting hepatic gluconeogenesis by regulation of STAT3 signal pathway and improving pancreatic beta-cell survival. PMID- 27203424 TI - Have LEGO Products Become More Violent? AB - Although television, computer games and the Internet play an important role in the lives of children they still also play with physical toys, such as dolls, cars and LEGO bricks. The LEGO company has become the world's largest toy manufacturer. Our study investigates if the LEGO company's products have become more violent over time. First, we analyzed the frequency of weapon bricks in LEGO sets. Their use has significantly increased. Second, we empirically investigated the perceived violence in the LEGO product catalogs from the years 1978-2014. Our results show that the violence of the depicted products has increased significantly over time. The LEGO Company's products are not as innocent as they used to be. PMID- 27203423 TI - Nipah Virus C Protein Recruits Tsg101 to Promote the Efficient Release of Virus in an ESCRT-Dependent Pathway. AB - The budding of Nipah virus, a deadly member of the Henipavirus genus within the Paramyxoviridae, has been thought to be independent of the host ESCRT pathway, which is critical for the budding of many enveloped viruses. This conclusion was based on the budding properties of the virus matrix protein in the absence of other virus components. Here, we find that the virus C protein, which was previously investigated for its role in antagonism of innate immunity, recruits the ESCRT pathway to promote efficient virus release. Inhibition of ESCRT or depletion of the ESCRT factor Tsg101 abrogates the C enhancement of matrix budding and impairs live Nipah virus release. Further, despite the low sequence homology of the C proteins of known henipaviruses, they all enhance the budding of their cognate matrix proteins, suggesting a conserved and previously unknown function for the henipavirus C proteins. PMID- 27203425 TI - Preoperative Neutrophil-to-Lymphocyte Ratio as a Predictive and Prognostic Factor for High-Grade Serous Ovarian Cancer. AB - OBJECTIVE: We aimed to demonstrate the clinical and prognostic significance of the preoperative neutrophil-to-lymphocyte ratio (NLR) in high-grade serous ovarian cancer (HGSC). METHODS: We retrospectively investigated 875 patients who underwent primary staging or debulking surgery for HGSC between April 2005 and June 2013 at our institution. None of these patients received neoadjuvant chemotherapy. NLR was defined as the absolute neutrophil count divided by the absolute lymphocyte count. Progression-free survival (PFS) and overall survival (OS) were analyzed with the Kaplan-Meier method and log-rank tests for univariate analyses. For multivariate analyses, Cox regression analysis was used to evaluate the effects of the prognostic factors, which were expressed as hazard ratios (HRs). RESULTS: The NLRs ranged from 0.30 to 24.0. The median value was 3.24 and used as the cutoff value to discriminate between the high-NLR (>=3.24) and low NLR (<3.24) groups. A high preoperative NLR level was associated with an advanced FIGO stage, increased CA125 level, more extensive ascites, worse cytoreduction outcome and chemoresistance. For univariate analyses, a high NLR was associated with reduced PFS (p<0.001) and OS (p<0.001). In multivariate analyses, a high NLR was still an independent predictor of PFS (p = 0.011), but not OS (p = 0.148). CONCLUSION: Our study demonstrated that NLR could reflect tumor burden and clinical outcomes to a certain extent and should be regarded as a predictive and prognostic parameter for HGSC. PMID- 27203427 TI - Residual Gastric Volume After Bowel Preparation With Polyethylene Glycol for Elective Colonoscopy: A Prospective Observational Study. AB - GOAL: To examine the residual gastric volume (RGV) in colonoscopy after bowel preparations with 3-L polyethylene glycol (PEG). BACKGROUND: Obstacles to high volume bowel preparation by anesthesia providers resulting from concerns over aspiration risk are common during colonoscopy. STUDY: Prospective measurements of RGV were performed in patients undergoing esophagogastroduodenoscopy (EGD) and morning colonoscopy with split-dose PEG preparation, patients undergoing EGD and afternoon colonoscopy with same-day PEG preparation, and patients undergoing EGD alone under moderate conscious sedation. Colonoscopy patients were allowed to ingest clear liquids until 2 hours before the procedure. Patients undergoing EGD alone were instructed to eat/drink nothing after midnight. RESULTS: There were 860 evaluated patients, including 330 in the split-dose preparation group, 100 in the same-day preparation group, and 430 in the EGD-only group. Baseline demographics and disease/medication factors were similar. The mean RGV in patients receiving the same-day preparation (35.4 mL or 0.56 mL/kg) was significantly higher than that in patients receiving the split-dose preparation (28.5 mL or 0.45 mL/kg) and in patients undergoing EGD alone (22.8 mL or 0.36 mL/kg) (P=0.023 and P<0.0001, respectively). Within the bowel-preparation groups, patients with fasting times of 2 to 3 hours had similar RGV compared with patients who had fasting times >3 hours. The shape of the distribution and the range of RGV among the 3 study groups were similar. No aspiration occurred in any group. CONCLUSIONS: PEG bowel preparations increase RGV mildly, but seem to have no clinical significance. These results support the current fasting guidelines for colonoscopy. PMID- 27203426 TI - Antimicrobial Functions of Lactoferrin Promote Genetic Conflicts in Ancient Primates and Modern Humans. AB - Lactoferrin is a multifunctional mammalian immunity protein that limits microbial growth through sequestration of nutrient iron. Additionally, lactoferrin possesses cationic protein domains that directly bind and inhibit diverse microbes. The implications for these dual functions on lactoferrin evolution and genetic conflicts with microbes remain unclear. Here we show that lactoferrin has been subject to recurrent episodes of positive selection during primate divergence predominately at antimicrobial peptide surfaces consistent with long term antagonism by bacteria. An abundant lactoferrin polymorphism in human populations and Neanderthals also exhibits signatures of positive selection across primates, linking ancient host-microbe conflicts to modern human genetic variation. Rapidly evolving sites in lactoferrin further correspond to molecular interfaces with opportunistic bacterial pathogens causing meningitis, pneumonia, and sepsis. Because microbes actively target lactoferrin to acquire iron, we propose that the emergence of antimicrobial activity provided a pivotal mechanism of adaptation sparking evolutionary conflicts via acquisition of new protein functions. PMID- 27203428 TI - The Gastric Remnant in Roux-en-Y Gastric Bypass: Challenges and Possibilities. AB - Laparoscopic Roux-en-Y gastric bypass (RYGB) is widely applied in the treatment of morbid obesity. Health personnel meeting these patients should thus be familiar with the potential clinical consequences of the modified anatomy induced by the surgery. After a RYGB, the stomach is left in situ after the closure of the upper part of the organ. This blind-ended gastric remnant may cause complications and surgical emergencies, but also opportunities for diagnostic and therapeutic intervention. The present review focuses on complications related to the gastric remnant including bleeding and acute dilatation in the early postoperative period and later adverse events such as gastroduodenal peptic disease, tumors, gastrogastric fistulas, and late dilatation. Opportunities offered by the remnant, including minimal invasive or open access for enteral nutrition, and therapeutic and diagnostic access to the bile ducts, the duodenum, and the gastric remnant, which is challenged by the modified anatomy, are discussed. Reversal of the gastric bypass and gastrointestinal reconstruction after esophageal resection have been commented on. The review aims to improve the awareness of issues related to the gastric remnant for physicians involved in the treatment and the follow-up of patients after a RYGB. PMID- 27203429 TI - Vanishing Bile Duct Syndrome in Hodgkin's Lymphoma: A Single Center Experience and Clinical Pearls. PMID- 27203430 TI - Subclinical Ascites Does Not Affect the Long-term Prognosis in Hepatitis B Virus related Cirrhosis Patients Receiving Antivirals. AB - BACKGROUND AND AIMS: This study evaluated the clinical significance of subclinical ascites in patients with hepatitis B virus-related cirrhosis treated with lamivudine (LMV) or entecavir (ETV). METHODS: This multicenter retrospective study involved 8 hospitals. Patients were classified by degree of ascites: (1) no ascites (no ascites on imaging, no diuretics), (2) subclinical ascites (small amount of ascites on imaging, no diuretics), and (3) clinical ascites (moderate to severe ascites or diuretics). RESULTS: Out of 501 patients, 336 (68%), 51 (10%), and 114 (23%) patients were classified as no-ascites, subclinical ascites, and clinical ascites, respectively. In all, 100 (20%) and 401 (80%) were treated with LMV and ETV, respectively. Over 58+/-24 months of follow-up, 105 patients (21%) developed hepatocellular carcinoma. The cumulative incidence of hepatocellular carcinoma did not differ between LMV-treated and ETV-treated patients (P=0.61); it was higher in the clinical-ascites group than the no ascites (P=0.054) and subclinical-ascites (P=0.03) groups, but it was comparable between the latter 2 (P=0.225). Forty-five patients (9%) died during follow-up. Survival was significantly shorter in the clinical-ascites group than the other 2 (both P<0.005), but it was comparable between no-ascites and subclinical-ascites groups (P=0.444). Multivariate analysis showed that mortality was significantly associated with prothrombin time [hazard ratio (HR)=2.42; 95% confidence interval (CI), 1.59-3.70], serum albumin (HR=0.54; 95% CI, 0.29-0.99), and presence of clinical ascites (HR=3.58; 95% CI, 1.54-8.30). CONCLUSIONS: Subclinical ascites did not affect prognosis in patients with hepatitis B virus-related cirrhosis receiving antiviral treatment. PMID- 27203433 TI - A Difference-in-Differences Approach to Assess the Effect of a Heat Action Plan on Heat-Related Mortality, and Differences in Effectiveness According to Sex, Age, and Socioeconomic Status (Montreal, Quebec). AB - BACKGROUND: The impact of heat waves on mortality and health inequalities is well documented. Very few studies have assessed the effectiveness of heat action plans (HAPs) on health, and none has used quasi-experimental methods to estimate causal effects of such programs. OBJECTIVES: We developed a quasi-experimental method to estimate the causal effects associated with HAPs that allows the identification of heterogeneity across subpopulations, and to apply this method specifically to the case of the Montreal (Quebec, Canada) HAP. METHODS: A difference-in differences approach was undertaken using Montreal death registry data for the summers of 2000-2007 to assess the effectiveness of the Montreal HAP, implemented in 2004, on mortality. To study equity in the effect of HAP implementation, we assessed whether the program effects were heterogeneous across sex (male vs. female), age (>= 65 years vs. < 65 years), and neighborhood education levels (first vs. third tertile). We conducted sensitivity analyses to assess the validity of the estimated causal effect of the HAP program. RESULTS: We found evidence that the HAP contributed to reducing mortality on hot days, and that the mortality reduction attributable to the program was greater for elderly people and people living in low-education neighborhoods. CONCLUSION: These findings show promise for programs aimed at reducing the impact of extreme temperatures and health inequities. We propose a new quasi-experimental approach that can be easily applied to evaluate the impact of any program or intervention triggered when daily thresholds are reached. Citation: Benmarhnia T, Bailey Z, Kaiser D, Auger N, King N, Kaufman J. 2016. A difference-in-differences approach to assess the effect of a heat action plan on heat-related mortality, and differences in effectiveness according to sex, age, and socioeconomic status (Montreal, Quebec). Environ Health Perspect 124:1694-1699; http://dx.doi.org/10.1289/EHP203. PMID- 27203434 TI - Comparing the Effectiveness of Bevacizumab to Ranibizumab in Patients with Exudative Age-Related Macular Degeneration. The BRAMD Study. AB - PURPOSE: To compare the effectiveness of bevacizumab and ranibizumab in the treatment of exudative age-related macular degeneration (AMD). DESIGN: Multicentre, randomized, controlled, double-masked clinical trial in 327 patients. The non-inferiority margin was 4 letters. PATIENTS: Patients >= 60 years of age with primary or recurrent sub- or juxtafoveal choroidal neovascularization (CNV) secondary to AMD with a total area of CNV < 12 disc areas and a best corrected visual acuity (BCVA) score between 20 and 78 letters on an EDTRS like chart in the study eye. METHODS: Monthly intravitreal injections with 1.25 mg bevacizumab or 0.5 mg ranibizumab were given during one year. Intention to treat with last observation carried forward analysis was performed. MAIN OUTCOME MEASURES: Primary outcome was the change in BCVA in the study eye from baseline to 12 months. RESULTS: The mean gain in BCVA was 5.1 (+/-14.1) letters in the bevacizumab group (n = 161) and 6.4 (+/-12.2) letters in the ranibizumab group (n = 166) (p = 0.37). The lower limit of the 95% confidence interval of the difference in BCVA gain was 3.72. The response to bevacizumab was more varied; 24% of patients showed a gain of >=15 letters, 11% a loss of >=15 letters and 65% a gain or loss < 15 letters compared to 19%, 5% and 76% respectively for ranibizumab (p = 0.038). No significant differences in absolute CRT and CRT change (p = 0.13) or in the presence of subretinal or intraretinal fluid (p = 0.14 and 0.10, respectively) were observed. However, the presence of any fluid on SD-OCT (subretinal and/or intraretinal) differed significantly (p = 0.020), with definite fluid on SD-OCT in 45% of the patients for bevacizumab versus 31% for ranibizumab. The occurrence of serious adverse events and adverse events was similar, with 34 SAEs and 256 AEs in the bevacizumab group and 37 SAEs and 299 AEs in the ranibizumab group (p = 0.87 and p = 0.48, respectively). CONCLUSIONS: Bevacizumab was not inferior to ranibizumab. The response to bevacizumab was more varied with higher percentages of both gainers and losers and more frequently observed retinal fluid on SD-OCT at 12 months when compared to the ranibizumab group. TRIAL REGISTRATION: Trialregister.nl NTR1704. PMID- 27203435 TI - Prevalence of Periodontitis in Patients with Established Rheumatoid Arthritis: A Swedish Population Based Case-Control Study. AB - INTRODUCTION: The possible hypothesis of a link between periodontitis and rheumatoid arthritis (RA), specifically anti-citrullinated protein antibody (ACPA) positive RA, prompted us to investigate the prevalence of periodontitis in the Swedish Epidemiological Investigation of RA (EIRA), a well-characterised population-based RA case-control cohort. METHODS: Periodontal status of 2,740 RA cases and 3,942 matched controls was retrieved through linking EIRA with the National Dental Health Registry (DHR), where dental diagnostic- and treatment codes on the adult Swedish population have been registered. Dental records from 100 cases and controls were reviewed to validate the periodontal diagnostic codes in DHR. RESULTS: The reviewed dental records confirmed 90% of the periodontitis diagnoses in DHR among RA cases, and 88% among controls. We found the positive predictive value of periodontitis diagnoses in the DHR to be 89% (95% CI 78 to 95%) with a sensitivity of 77% (95% CI: 65 to 86%). In total, 86% of EIRA participants were identified in DHR. The risk for periodontitis increased by age and current smoking status in both cases as well as controls. No significant differences in prevalence of periodontal disease in terms of gingivitis, periodontitis, peri-implantitis or increased risk for periodontitis or peri implantitis were observed between RA cases and controls. In addition, there was no difference on the basis of seropositivity, ACPA or rheumatoid factor (RF), among patients with RA. CONCLUSIONS: Our data verify that smoking and ageing are risk factors for periodontitis, both in RA and controls. We found no evidence of an increased prevalence of periodontitis in patients with established RA compared to healthy controls, and no differences based on ACPA or RF status among RA subjects. PMID- 27203436 TI - Immune Cell Targets of Infection at the Tick-Skin Interface during Powassan Virus Transmission. AB - Powassan virus (POWV) is a tick-borne flavivirus that can result in a severe neuroinvasive disease with 50% of survivors displaying long-term neurological sequelae. Human POWV cases have been documented in Canada, the United States, and Russia. Although the number of reported POWV human cases has increased in the past fifteen years, POWV remains one of the less studied human pathogenic flaviviruses. Ixodes ticks are the vectors for POWV, and the virus is transmitted to a host's skin very early during the tick feeding process. Central to the successful transmission of a tick-borne pathogen are complex interactions between the host immune response and early tick-mediated immunomodulation, all of which initially occur at the skin interface. In our prior work, we examined the cutaneous immune gene expression during the early stages of POWV-infected Ixodes scapularis feeding. The present study serves to further investigate the skin interface by identifying early cell targets of infection at the POWV-infected tick feeding site. An in vivo infection model consisting of POWV-infected ticks feeding on mice for short durations was used in this study. Skin biopsies from the tick feeding sites were harvested at various early time points, enabling us to examine the skin histopathology and detect POWV viral antigen in immune cells present at the tick feeding site. The histopathology from the present study demonstrates that neutrophil and mononuclear cell infiltrates are recruited earlier to the feeding site of a POWV-infected tick versus an uninfected tick. This is the first report demonstrating that macrophages and fibroblasts contain POWV antigens, which suggests that they are early cellular targets of infection at the tick feeding site. These data provide key insights towards defining the complex interactions between the host immune response and early tick-mediated immunomodulation. PMID- 27203437 TI - High Efficiency CRISPR/Cas9-mediated Gene Editing in Primary Human T-cells Using Mutant Adenoviral E4orf6/E1b55k "Helper" Proteins. AB - Many future therapeutic applications of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 and related RNA-guided nucleases are likely to require their use to promote gene targeting, thus necessitating development of methods that provide for delivery of three components-Cas9, guide RNAs and recombination templates-to primary cells rendered proficient for homology directed repair. Here, we demonstrate an electroporation/transduction codelivery method that utilizes mRNA to express both Cas9 and mutant adenoviral E4orf6 and E1b55k helper proteins in association with adeno-associated virus (AAV) vectors expressing guide RNAs and recombination templates. By transiently enhancing target cell permissiveness to AAV transduction and gene editing efficiency, this novel approach promotes efficient gene disruption and/or gene targeting at multiple loci in primary human T-cells, illustrating its broad potential for application in translational gene editing. PMID- 27203438 TI - Mesenchymal Stem Cells Deliver Exogenous MicroRNA-let7c via Exosomes to Attenuate Renal Fibrosis. AB - The advancement of microRNA (miRNA) therapies has been hampered by difficulties in delivering miRNA to the injured kidney in a robust and sustainable manner. Using bioluminescence imaging in mice with unilateral ureteral obstruction (UUO), we report that mesenchymal stem cells (MSCs), engineered to overexpress miRNA let7c (miR-let7c-MSCs), selectively homed to damaged kidneys and upregulated miR let7c gene expression, compared with nontargeting control (NTC)-MSCs. miR-let7c MSC therapy attenuated kidney injury and significantly downregulated collagen IValpha1, metalloproteinase-9, transforming growth factor (TGF)-beta1, and TGF beta type 1 receptor (TGF-betaR1) in UUO kidneys, compared with controls. In vitro analysis confirmed that the transfer of miR-let7c from miR-let7c-MSCs occurred via secreted exosomal uptake, visualized in NRK52E cells using cyc3 labeled pre-miRNA-transfected MSCs with/without the exosomal inhibitor, GW4869. The upregulated expression of fibrotic genes in NRK52E cells induced by TGF-beta1 was repressed following the addition of isolated exosomes or indirect coculture of miR-let7c-MSCs, compared with NTC-MSCs. Furthermore, the cotransfection of NRK52E cells using the 3'UTR of TGF-betaR1 confirmed that miR-let7c attenuates TGF-beta1-driven TGF-betaR1 gene expression. Taken together, the effective antifibrotic function of engineered MSCs is able to selectively transfer miR let7c to damaged kidney cells and will pave the way for the use of MSCs for therapeutic delivery of miRNA targeted at kidney disease. PMID- 27203439 TI - Translational Implications for Off-the-shelf Immune Cells Expressing Chimeric Antigen Receptors. AB - Chimeric antigen receptor (CAR) endows specificity to T-cells independent of human leukocyte antigen (HLA). This enables one immunoreceptor to directly target the same surface antigen on different subsets of tumor cells from multiple HLA disparate recipients. Most approaches manufacture individualized CAR(+)T-cells from the recipient or HLA-compatible donor, which are revealing promising clinical results. This is the impetus to broaden the number of patients eligible to benefit from adoptive immunotherapy such as to infuse third-party donor derived CAR(+)T-cells. This will overcome issues associated with (i) time to manufacture T-cells, (ii) cost to generate one product for one patient, (iii) inability to generate a product from lymphopenic patients or patient's immune cells fail to complete the manufacturing process, and (iv) heterogeneity of T cell products produced for or from individual recipients. Establishing a biobank of allogeneic genetically modified immune cells from healthy third-party donors, which are cryopreserved and validated in advance of administration, will facilitate the centralizing manufacturing and widespread distribution of CAR(+)T cells to multiple points-of-care in a timely manner. To achieve this, it is necessary to engineer an effective strategy to avoid deleterious allogeneic immune responses leading to toxicity and rejection. We review the strategies to establish "off-the-shelf" donor-derived biobanks for human application of CAR(+)T cells as a drug. PMID- 27203440 TI - Genome Therapy of Myotonic Dystrophy Type 1 iPS Cells for Development of Autologous Stem Cell Therapy. AB - Myotonic dystrophy type 1 (DM1) is caused by expanded Cytosine-Thymine-Guanine (CTG) repeats in the 3'-untranslated region (3' UTR) of the Dystrophia myotonica protein kinase (DMPK) gene, for which there is no effective therapy. The objective of this study is to develop genome therapy in human DM1 induced pluripotent stem (iPS) cells to eliminate mutant transcripts and reverse the phenotypes for developing autologous stem cell therapy. The general approach involves targeted insertion of polyA signals (PASs) upstream of DMPK CTG repeats, which will lead to premature termination of transcription and elimination of toxic mutant transcripts. Insertion of PASs was mediated by homologous recombination triggered by site-specific transcription activator-like effector nuclease (TALEN)-induced double-strand break. We found genome-treated DM1 iPS cells continue to maintain pluripotency. The insertion of PASs led to elimination of mutant transcripts and complete disappearance of nuclear RNA foci and reversal of aberrant splicing in linear-differentiated neural stem cells, cardiomyocytes, and teratoma tissues. In conclusion, genome therapy by insertion of PASs upstream of the expanded DMPK CTG repeats prevented the production of toxic mutant transcripts and reversal of phenotypes in DM1 iPS cells and their progeny. These genetically-treated iPS cells will have broad clinical application in developing autologous stem cell therapy for DM1. PMID- 27203441 TI - CRISPR Repair Reveals Causative Mutation in a Preclinical Model of Retinitis Pigmentosa. AB - Massive parallel sequencing enables identification of numerous genetic variants in mutant organisms, but determining pathogenicity of any one mutation can be daunting. The most commonly studied preclinical model of retinitis pigmentosa called the "rodless" (rd1) mouse is homozygous for two mutations: a nonsense point mutation (Y347X) and an intronic insertion of a leukemia virus (Xmv-28). Distinguishing which mutation causes retinal degeneration is still under debate nearly a century after the discovery of this model organism. Here, we performed gene editing using the CRISPR/Cas9 system and demonstrated that the Y347X mutation is the causative variant of disease. Genome editing in the first generation produced animals that were mosaic for the corrected allele but still showed neurofunction preservation despite low repair frequencies. Furthermore, second-generation CRISPR-repaired mice showed an even more robust rescue and amelioration of the disease. This predicts excellent outcomes for gene editing in diseased human tissue, as Pde6b, the mutated gene in rd1 mice, has an orthologous intron-exon relationship comparable with the human PDE6B gene. Not only do these findings resolve the debate surrounding the source of neurodegeneration in the rd1 model, but they also provide the first example of homology-directed recombination-mediated gene correction in the visual system. PMID- 27203442 TI - Neural Stem Cells Engineered to Express Three Therapeutic Factors Mediate Recovery from Chronic Stage CNS Autoimmunity. AB - Treatment of chronic neurodegenerative diseases such as multiple sclerosis (MS) remains a major challenge. Here we genetically engineer neural stem cells (NSCs) to produce a triply therapeutic cocktail comprising IL-10, NT-3, and LINGO-1-Fc, thus simultaneously targeting all mechanisms underlie chronicity of MS in the central nervous system (CNS): persistent inflammation, loss of trophic support for oligodendrocytes and neurons, and accumulation of neuroregeneration inhibitors. After transplantation, NSCs migrated into the CNS inflamed foci and delivered these therapeutic molecules in situ. NSCs transduced with one, two, or none of these molecules had no or limited effect when injected at the chronic stage of experimental autoimmune encephalomyelitis; cocktail-producing NSCs, in contrast, mediated the most effective recovery through inducing M2 macrophages/microglia, reducing astrogliosis, and promoting axonal integrity and endogenous oligodendrocyte/neuron differentiation. These engineered NSCs simultaneously target major mechanisms underlying chronicity of multiple sclerosis (MS) and encephalomyelitis (EAE), thus representing a novel and potentially effective therapy for the chronic stage of MS, for which there is currently no treatment available. PMID- 27203443 TI - Strand and Cell Type-specific Function of microRNA-126 in Angiogenesis. AB - microRNAs or miRs have been shown to be pivotal modulators of vascular development. The strand and cell type-specific function of miR-126 in angiogenesis, especially pathological angiogenesis, remains poorly defined. We characterized the retinal vascular phenotype of miR-126-/- mice, and tested the function of miR-126 strands (miR-126-3p and -5p) using in vitro angiogenesis models and a mouse model of neovascular age-related macular degeneration. We found that miR-126 is critical for retinal vascular development but has dual function in pathological angiogenesis. miR-126-/- mice showed defective postnatal retinal vascular development and remodeling, which is partially rescued by genetic knockout of its target gene Spred-1. Surprisingly, either silencing miR 126-3p by LNA-antimiR or overexpressing miR-126-3p by miRNA mimic repressed laser induced choroidal neovascularization. To dissect the underlying mechanism, we found in endothelial cells, silencing of miR-126-3p repressed angiogenesis, while overexpression of miR-126-5p enhanced angiogenesis. However, in retinal pigment epithelial cells, miR-126-3p repressed vascular endothelial growth factor (VEGF A) expression via a novel mechanism of regulating alphaB-Crystallin promoter activity and by directly targeting VEGF-A 3'-untranslated region. These findings provide first genetic evidence that miR-126 is required for the development of different retinal vascular layers, and also uncover a strand and cell type specific function of miR-126 in ocular pathological angiogenesis. PMID- 27203444 TI - Complete Spectrum of CRISPR/Cas9-induced Mutations on HBV cccDNA. AB - Hepatitis B virus (HBV) causes chronic infections that cannot yet be cured. The virus persists in infected hepatocytes, because covalently closed circular DNA (cccDNA), the template for the transcription of viral RNAs, is stable in nondividing cells. Antiviral therapies with nucleoside analogues inhibit HBV DNA synthesis in capsids in the cytoplasm of infected hepatocytes, but do not destroy nuclear cccDNA. Because over 200 million people are still infected, a cure for chronic hepatitis B (CHB) has become one of the major challenges in antiviral therapy. As a first step toward the development of curative therapies, we previously demonstrated that the CRISPR/Cas9 system can be used to functionally inactivate cccDNA derived from infectious HBV. Moreover, some evidence suggests that certain cytokines might induce an APOBEC-mediated cascade leading to the destruction of cccDNA. In this report we investigated whether a combination of the two mechanisms could act synergistically to inactivate cccDNA. Using next generation sequencing (NGS), we determined the complete spectrum of mutations in cccDNA following Cas9 cleavage and repair by nonhomologous end joining (NHEJ). We found that over 90% of HBV DNA was cleaved by Cas9. In addition our results showed that editing of HBV DNA after Cas9 cleavage is at least 15,000 times more efficient that APOBEC-mediated cytosine deamination following treatment of infected cells with interferon alpha (IFNalpha). We also found that a previously used method to detect cytosine deaminated DNA, termed 3D-PCR, overestimates the amount and frequency of edited HBV DNA. Taken together, our results demonstrated that the CRISPR/Cas9 system is so far the best method to functionally inactivate HBV cccDNA and provide a cure for CHB. PMID- 27203445 TI - Phase 1 Study of Intravenous Oncolytic Poxvirus (vvDD) in Patients With Advanced Solid Cancers. AB - We have conducted a phase 1 study of intravenous vvDD, a Western Reserve strain oncolytic vaccinia virus, on 11 patients with standard treatment-refractory advanced colorectal or other solid cancers. The primary endpoints were maximum tolerated dose and associated toxicity while secondary endpoints were pharmacokinetics, pharmacodynamics, immune responses, and antitumor activity. No dose-limiting toxicities and treatment related severe adverse events were observed. The most common adverse events were grades 1/2 flu-like symptoms. Virus genomes were detectable in the blood 15-30 minutes after virus administration in a dose-dependent manner. There was evidence of a prolonged virus replication in tumor tissues in two patients, but no evidence of virus replication in non-tumor tissues, except a healed injury site and an oral thrush. Over 100-fold of anti viral antibodies were induced in patients' sera. A strong induction of inflammatory and Th1, but not Th2 cytokines, suggested a potent Th1-mediated immunity against the virus and possibly the cancer. One patient showed a mixed response on PET-CT with resolution of some liver metastases, and another patient with cutaneous melanoma demonstrated clinical regression of some lesions. Given the confirmed safety, further trials evaluating intravenous vvDD in combination with therapeutic transgenes, immune checkpoint blockade or complement inhibitors, are warranted. PMID- 27203447 TI - Studying Protein-Protein Binding through T-Jump Induced Dissociation: Transient 2D IR Spectroscopy of Insulin Dimer. AB - Insulin homodimer associates through the coupled folding and binding of two partially disordered monomers. We aim to understand this dynamics by observing insulin dimer dissociation initiated with a nanosecond temperature jump using transient two-dimensional infrared spectroscopy (2D IR) of amide I vibrations. With the help of equilibrium FTIR and 2D IR spectra, and through a systematic study of the dependence of dissociation kinetics on temperature and insulin concentration, we are able to decompose and analyze the spectral evolution associated with different secondary structures. We find that the dissociation under all conditions is characterized by two processes whose influence on the kinetics varies with temperature: the unfolding of the beta sheet at the dimer interface observed as exponential kinetics between 250 and 1000 MUs and nonexponential kinetics between 5 and 150 MUs that we attribute to monomer disordering. Microscopic reversibility arguments lead us to conclude that dimer association requires significant conformational changes within the monomer in concert with the folding of the interfacial beta sheet. While our data indicates a more complex kinetics, we apply a two-state model to the beta-sheet unfolding kinetics to extract thermodynamic parameters and kinetic rate constants. The association rate constant, ka (23 degrees C) = 8.8 * 10(5) M(-1) s(-1) (pH 0, 20% EtOD), is approximately 3 orders of magnitude slower than the calculated diffusion limited association rate, which is explained by the significant destabilizing effect of ethanol on the dimer state and the highly positive charge of the monomers at this pH. PMID- 27203446 TI - Boosting Central Nervous System Axon Regeneration by Circumventing Limitations of Natural Cytokine Signaling. AB - Retinal ganglion cells (RGCs) do not normally regenerate injured axons, but die upon axotomy. Although IL-6-like cytokines are reportedly neuroprotective and promote optic nerve regeneration, their overall regenerative effects remain rather moderate. Here, we hypothesized that direct activation of the gp130 receptor by the designer cytokine hyper-IL-6 (hIL-6) might induce stronger RGC regeneration than natural cytokines. Indeed, hIL-6 stimulated neurite growth of adult cultured RGCs with significantly higher efficacy than CNTF or IL-6. This neurite growth promoting effect could be attributed to stronger activation of the JAK/STAT3 and PI3K/AKT/mTOR signaling pathways and was also observed in peripheral dorsal root ganglion neurons. Moreover, hIL-6 abrogated axon growth inhibition by central nervous system (CNS) myelin. Remarkably, continuous hIL-6 expression upon RGC-specific AAV transduction after optic nerve crush exerted stronger axon regeneration than other known regeneration promoting treatments such as lens injury and PTEN knockout, with some axons growing through the optic chiasm 6 weeks after optic nerve injury. Combination of hIL-6 with RGC-specific PTEN knockout further enhanced optic nerve regeneration. Therefore, direct activation of gp130 signaling might be a novel, clinically applicable approach for robust CNS repair. PMID- 27203448 TI - Unusual Synthetic Pathway for an {Fe(NO)2}(9) Dinitrosyl Iron Complex (DNIC) and Insight into DNIC Electronic Structure via Nuclear Resonance Vibrational Spectroscopy. AB - Dinitrosyl iron complexes (DNICs) are among the most abundant NO-derived cellular species. Monomeric DNICs can exist in the {Fe(NO)2}(9) or {Fe(NO)2}(10) oxidation state (in the Enemark-Feltham notation). However, experimental studies of analogous DNICs in both oxidation states are rare, which prevents a thorough understanding of the differences in the electronic structures of these species. Here, the {Fe(NO)2}(9) DNIC [Fe(dmp)(NO)2](OTf) (1; dmp = 2,9-dimethyl-1,10 phenanthroline) is synthesized from a ferrous precursor via an unusual pathway, involving disproportionation of an {FeNO}(7) complex to yield the {Fe(NO)2}(9) DNIC and a ferric species, which is subsequently reduced by NO gas to generate a ferrous complex that re-enters the reaction cycle. In contrast to most {Fe(NO)2}(9) DNICs with neutral N-donor ligands, 1 exhibits high solution stability and can be characterized structurally and spectroscopically. Reduction of 1 yields the corresponding {Fe(NO)2}(10) DNIC [Fe(dmp)(NO)2] (2). The Mossbauer isomer shift of 2 is 0.08 mm/s smaller than that of 1, which indicates that the iron center is slightly more oxidized in the reduced complex. The nuclear resonance vibrational spectra (NRVS) of 1 and 2 are distinct and provide direct experimental insight into differences in bonding in these complexes. In particular, the symmetric out-of-plane Fe-N-O bending mode is shifted to higher energy by 188 cm(-1) in 2 in comparison to 1. Using quantum chemistry centered normal coordinate analysis (QCC-NCA), this is shown to arise from an increase in Fe-NO bond order and a stiffening of the Fe(NO)2 unit upon reduction of 1 to 2. DFT calculations demonstrate that the changes in bonding arise from an iron centered reduction which leads to a distinct increase in Fe-NO pi-back-bonding in {Fe(NO)2}(10) DNICs in comparison to the corresponding {Fe(NO)2}(9) complexes, in agreement with all experimental findings. Finally, the implications of the electronic structure of DNICs for their reactivity are discussed, especially with respect to N-N bond formation in NO reductases. PMID- 27203453 TI - Unraveling the Mechanism of Nanoscale Mechanical Reinforcement in Glassy Polymer Nanocomposites. AB - The mechanical reinforcement of polymer nanocomposites (PNCs) above the glass transition temperature, Tg, has been extensively studied. However, not much is known about the origin of this effect below Tg. In this Letter, we unravel the mechanism of PNC reinforcement within the glassy state by directly probing nanoscale mechanical properties with atomic force microscopy and macroscopic properties with Brillouin light scattering. Our results unambiguously show that the "glassy" Young's modulus in the interfacial polymer layer of PNCs is two times higher than in the bulk polymer, which results in significant reinforcement below Tg. We ascribe this phenomenon to a high stretching of the chains within the interfacial layer. Since the interfacial chain packing is essentially temperature independent, these findings provide a new insight into the mechanical reinforcement of PNCs also above Tg. PMID- 27203452 TI - Teaching basic life support with an automated external defibrillator using the two-stage or the four-stage teaching technique. AB - INTRODUCTION: Laypersons often hesitate to perform basic life support (BLS) and use an automated external defibrillator (AED) because of self-perceived lack of knowledge and skills. Training may reduce the barrier to intervene. Reduced training time and costs may allow training of more laypersons. The aim of this study was to compare BLS/AED skills' acquisition and self-evaluated BLS/AED skills after instructor-led training with a two-stage versus a four-stage teaching technique. METHODS: Laypersons were randomized to either two-stage or four-stage teaching technique courses. Immediately after training, the participants were tested in a simulated cardiac arrest scenario to assess their BLS/AED skills. Skills were assessed using the European Resuscitation Council BLS/AED assessment form. The primary endpoint was passing the test (17 of 17 skills adequately performed). A prespecified noninferiority margin of 20% was used. RESULTS: The two-stage teaching technique (n=72, pass rate 57%) was noninferior to the four-stage technique (n=70, pass rate 59%), with a difference in pass rates of -2%; 95% confidence interval: -18 to 15%. Neither were there significant differences between the two-stage and four-stage groups in the chest compression rate (114+/-12 vs. 115+/-14/min), chest compression depth (47+/-9 vs. 48+/-9 mm) and number of sufficient rescue breaths between compression cycles (1.7+/-0.5 vs. 1.6+/-0.7). In both groups, all participants believed that their training had improved their skills. CONCLUSION: Teaching laypersons BLS/AED using the two-stage teaching technique was noninferior to the four-stage teaching technique, although the pass rate was -2% (95% confidence interval: -18 to 15%) lower with the two-stage teaching technique. PMID- 27203454 TI - Preconception counseling after bariatric surgery. AB - Obesity has increased exponentially in the United States, affecting over 78 million individuals. As the rates of obesity increase, providers encounter more women with a history of bariatric surgery. Certain bariatric procedures can change how essential nutrients are absorbed. Preconception counseling assists in identifying potential deficiencies early. PMID- 27203455 TI - Diagnosis and treatment for chronic migraine. AB - Migraine is a debilitating headache disorder that is underdiagnosed and undertreated worldwide, partially attributable to misdiagnosis and expectations of poor treatment outcomes. This article provides a review of chronic migraine, including pathophysiology, burden, diagnosis, and management, with special emphasis on the role of NPs. PMID- 27203458 TI - An overview of antithrombotics in ischemic stroke. PMID- 27203457 TI - Primary care management of depression in children and adolescents. PMID- 27203460 TI - The Author File: Jason W. Chin. PMID- 27203461 TI - Fluorescent peptide biosensor for monitoring CDK4/cyclin D kinase activity in melanoma cell extracts, mouse xenografts and skin biopsies. AB - Melanoma constitutes the most aggressive form of skin cancer, which further metastasizes into a deadly form of cancer. The p16(INK4a)-Cyclin D-CDK4/6-pRb pathway is dysregulated in 90% of melanomas. CDK4/Cyclin D kinase hyperactivation, associated with mutation of CDK4, amplification of Cyclin D or loss of p16(INK4a) leads to increased risk of developing melanoma. This kinase therefore constitutes a key biomarker in melanoma and an emerging pharmacological target, however there are no tools enabling direct detection or quantification of its activity. Here we report on the design and application of a fluorescent peptide biosensor to quantify CDK4 activity in melanoma cell extracts, skin biopsies and melanoma xenografts. This biosensor provides sensitive means of comparing CDK4 activity between different melanoma cell lines and further responds to CDK4 downregulation by siRNA or small-molecule inhibitors. By affording means of monitoring CDK4 hyperactivity consequent to cancer-associated molecular alterations in upstream signaling pathways that converge upon this kinase, this biosensor offers an alternative to immunological identification of melanoma-specific biomarkers, thereby constituting an attractive tool for diagnostic purposes, providing complementary functional information to histological analysis, of particular utility for detection of melanoma onset in precancerous lesions. This is indeed the first fluorescent peptide biosensor which has been successfully implemented to monitor kinase activity in skin samples and melanoma tumour xenografts. Moreover by enabling to monitor response to CDK4 inhibitors, this biosensor constitutes an attractive companion assay to identify compounds of therapeutic relevance for melanoma. PMID- 27203462 TI - Construction of fluorescent polymeric nano-thermometers for intracellular temperature imaging: A review. AB - Multitudinous biochemical reactions occur in living cells, creating and releasing free energy to impel numerous cellular activities. Surplus energy is expelled as heat and resulted in elevated temperature, which induce control of gene expression, tumour metabolism and etc. Sensitive measurement of temperature on nanoscale in cells with ideal fluorescent probes is a great challenge in many areas. By taking the advantages of polymers in tunable critical solution temperature range and good biocompatibility, fluorescent polymeric thermometers (FPT) have drawn extensive attention because they are capable of accurate monitoring temperature with high spatial resolution at cellular level. This review offers a general overview of recent examples of FPT working in cells. The strategy for design and synthesis of the FPT has been highlighted. Furthermore, the applications of the constructed FPT for intracellular temperature variations under normal and external stimuli conditions have been discussed. Deep understanding of these aspects would lead to improvement in designing of unique FPT with real function and applications for intracellular temperature sensing. It will pave a new way not only for the study of intrinsic relationship between temperature and organelle function, but also provide the possibility for deep understanding of intracellular biological processes. PMID- 27203463 TI - An immunochromatographic biosensor combined with a water-swellable polymer for automatic signal generation or amplification. AB - An immunochromatographic assay (ICA) strip is one of the most widely used platforms in the field of point-of-care biosensors for the detection of various analytes in a simple, fast, and inexpensive manner. Currently, several approaches for sequential reactions in ICA platforms have improved their usability, sensitivity, and versatility. In this study, a new, simple, and low-cost approach using automatic sequential-reaction ICA strip is described. The automatic switching of a reagent pad from separation to attachment to the test membrane was achieved using a water-swellable polymer. The reagent pad was dried with an enzyme substrate for signal generation or with signal-enhancing materials. The strip design and system operation were confirmed by the characterization of the raw materials and flow analysis. We demonstrated the operation of the proposed sensor by using various chemical reaction-based assays, including metal-ion amplification, enzyme-colorimetric reaction, and enzyme-catalyzed chemiluminescence. Furthermore, by employing C-reactive protein as a model, we successfully demonstrated that the new water-swellable polymer-based ICA sensor can be utilized to detect biologically relevant analytes in human serum. PMID- 27203464 TI - Reply to comment on: 'The influence of antioxidant THPC on the properties of polymer gel dosimeter'. PMID- 27203465 TI - Associations between birth weight and colon and rectal cancer risk in adulthood. AB - BACKGROUND: Birth weight has inconsistent associations with colorectal cancer, possibly due to different anatomic features of the colon versus the rectum. The aim of this study was to investigate the association between birth weight and colon and rectal cancers separately. METHODS: 193,306 children, born from 1936 to 1972, from the Copenhagen School Health Record Register were followed prospectively in Danish health registers. Colon and rectal cancer cases were defined using the International Classification of Disease version 10 (colon: C18.0-18.9, rectal: 19.9 and 20.9). Only cancers classified as adenocarcinomas were included in the analyses. Cox regressions were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Analyses were stratified by birth cohort and sex. RESULTS: During 3.8 million person-years of follow-up, 1465 colon and 961 rectal adenocarcinomas were identified. No significant sex differences were observed; therefore combined results are presented. Birth weight was positively associated with colon cancers with a HR of 1.14 (95% CI, 1.04-1.26) per kilogram of birth weight. For rectal cancer a significant association was not observed for birth weights below 3.5kg. Above 3.5kg an inverse association was observed (at 4.5kg, HR=0.77 [95% CI, 0.61-0.96]). Further, the associations between birth weight and colon and rectal cancer differed significantly from each other (p=0.006). CONCLUSIONS: Birth weight is positively associated with the risk of adult colon cancer, whereas the results for rectal cancer were inverse only above values of 3.5kg. The results underline the importance of investigating colon and rectal cancer as two different entities. PMID- 27203466 TI - Characterization of anthropogenic impacts in a large urban center by examining the spatial distribution of halogenated flame retardants. AB - Anthropogenic impacts have continuously intensified in mega urban centers with increasing urbanization and growing population. The spatial distribution pattern of such impacts can be assessed with soil halogenated flame retardants (HFRs) as HFRs are mostly derived from the production and use of various consumer products. In the present study, soil samples were collected from the Pearl River Delta (PRD), a large urbanized region in southern China, and its surrounding areas and analyzed for a group of HFRs, i.e., polybrominated diphenyl ethers (PBDEs), decabromodiphenyl ethane, bis(hexachlorocyclopentadieno)cyclooctane (DP) and hexabromobenzene. The sum concentrations of HFRs and PBDEs were in the ranges of 0.66-6500 and 0.37-5700 (mean: 290 and 250) ng g(-1) dry weight, respectively, around the middle level of the global range. BDE-209 was the predominant compound likely due to the huge amounts of usage and its persistence. The concentrations of HFRs were greater in the land-use types of residency, industry and landfill than in agriculture, forestry and drinking water source, and were also greater in the central PRD than in its surrounding areas. The concentrations of HFRs were moderately significantly (r(2) = 0.32-0.57; p < 0.05) correlated with urbanization levels, population densities and gross domestic productions in fifteen administrative districts. The spatial distribution of DP isomers appeared to be stereoselective as indicated by the similarity in the spatial patterns for the ratio of anti-DP versus the sum of DP isomers (fanti-DP) and DP concentrations. Finally, the concentrations of HFRs sharply decreased with increasing distance from an e-waste recycling site, indicating that e-waste derived HFRs largely remained in local soil. PMID- 27203467 TI - The washout effects of rainfall on atmospheric particulate pollution in two Chinese cities. AB - Though rainfall is recognized as one of the main mechanisms to reduce atmospheric particulate pollution, few studies have quantified this effect, particularly the corresponding lag effect and threshold. This study aimed to investigate the association between rainfall and air quality using a distributed lag non-linear model. Daily data on ambient PM2.5 and PM2.5-10 (particulate matter with an aerodynamic diameter less than 2.5 MUm and from 2.5 to 10 MUm) and meteorological factors were collected in Guangzhou and Xi'an from 2013 to 2014. A better washout effect was found for PM2.5-10 than for PM2.5, and the rainfall thresholds for both particle fractions were 7 mm in Guangzhou and 1 mm in Xi'an. The decrease in PM2.5 levels following rain lasted for 3 and 6 days in Guangzhou and Xi'an, respectively. Rainfall had a better washout effect in Xi'an compared with that in Guangzhou. Findings from this study contribute to a better understanding of the washout effects of rainfall on particulate pollution, which may help to understand the category and sustainability of dust-haze and enforce anthropogenic control measures in time. PMID- 27203468 TI - Ecotoxicity and genotoxicity of cadmium in different marine trophic levels. AB - Cadmium ecotoxicity and genotoxicity was assessed in three representative species of different trophic levels of marine ecosystems - the calanoid copepod Acartia tonsa, the decapod shrimp, Palaemon varians and the pleuronectiform fish Solea senegalensis. Ecotoxicity endpoints assessed in this study were adult survival, hatching success and larval development ratio (LDR) for A. tonsa, survival of the first larval stage (zoea I) and post-larvae of P. varians, egg and larvae survival, as well as the presence of malformations in the larval stage of S. senegalensis. In vivo genotoxicity was assessed on adult A. tonsa, the larval and postlarval stage of P. varians and newly hatched larvae of S. senegalensis using the comet assay. Results showed that the highest sensitivity to cadmium is displayed by A. tonsa, with the most sensitive endpoint being the LDR of nauplii to copepodites. Sole eggs displayed the highest tolerance to cadmium compared to the other endpoints evaluated for all tested species. Recorded cadmium toxicity was (by increasing order): S. senegalensis eggs < P. varians post-larvae < P. varians zoea I < S. senegalensis larvae < A. tonsa eggs < A. tonsa LDR. DNA damage to all species exposed to cadmium increased with increasing concentrations. Overall, understanding cadmium chemical speciation is paramount to reliably evaluate the effects of this metal in marine ecosystems. Cadmium is genotoxic to all three species tested and therefore may differentially impact individuals and populations of marine taxa. As A. tonsa was the most sensitive species and occupies a lower trophic level, it is likely that cadmium contamination may trigger bottom-up cascading effects in marine trophic interactions. PMID- 27203469 TI - Neutral mood induction during reconsolidation reduces accuracy, but not vividness and anxiety of emotional episodic memories. AB - BACKGROUND AND OBJECTIVES: Consolidated memories become labile upon reactivation and as a result have to go through reconsolidation to become re-stabilized. This property of memory may potentially be used to reduce the impact of highly negative episodic memories. Because detailed and vivid negative memories are mediated by high arousal, if arousal is lessened during reconsolidation, memory accuracy and vividness should diminish. In this study, we examined this hypothesis. METHODS: Participants (N = 72) viewed a stressful, suspenseful video on Day 1 to develop negative episodic memories. Then, 24-29 h later, they saw a brief reminder of the stressful video (or not), and then viewed a neutral, calming (or positive) video. Another 24-29 h later, participants were tested on the accuracy, vividness, and anxiety associated with their memory of the stressful video on Day 1. RESULTS: Participants who watched the reminder and then the neutral video showed reduced memory accuracy compared to participants in the other groups. Despite the reduction in memory accuracy, their memory vividness and anxiety associated with the stressful video did not decrease. LIMITATIONS: The use of undergraduates prevents generalizations to clinical populations. Also, the study did not test long-term memories that were more than 2 days old. CONCLUSIONS: Neutral mood induction during reconsolidation reduces the accuracy of highly negative episodic memories. PMID- 27203470 TI - Estimation of mean first passage time for bursty gene expression. AB - Gene expression is an intrinsically noisy process, typically, producing mRNAs and proteins in bursts. An important description of such stochastic processes can be done in terms of the mean first passage time (MFPT), i.e., the time taken by mRNAs/proteins to reach a particular threshold. We study the role of burstiness on MFPT and obtain an analytical expression for different models of transcriptional and translational bursts. Our analytical results and numerical simulations confirm that MFPT monotonically decreases with burstiness. PMID- 27203472 TI - The International Congress on Integrative Medicine and Health (ICIMH), Las Vegas, Nevada, USA May 17-20, 2016. PMID- 27203471 TI - Fossil and Nonfossil Sources of Organic and Elemental Carbon Aerosols in the Outflow from Northeast China. AB - Source quantification of carbonaceous aerosols in the Chinese outflow regions still remains uncertain despite their high mass concentrations. Here, we unambiguously quantified fossil and nonfossil contributions to elemental carbon (EC) and organic carbon (OC) of total suspended particles (TSP) from a regional receptor site in the outflow of Northeast China using radiocarbon measurement. OC and EC concentrations were lower in summer, representing mainly marine air, than in other seasons, when air masses mostly traveled over continental regions in Mongolia and northeast China. The annual-mean contribution from fossil-fuel combustion to EC was 76 +/- 11% (0.1-1.3 MUg m(-3)). The remaining 24 +/- 11% (0.03-0.42 MUg m(-3)) was attributed to biomass burning, with slightly higher contribution in the cold period (~31%) compared to the warm period (~21%) because of enhanced emissions from regional biomass combustion sources in China. OC was generally dominated by nonfossil sources, with an annual average of 66 +/- 11% (0.5-2.8 MUg m(-3)), approximately half of which was apportioned to primary biomass-burning sources (34 +/- 6%). In winter, OC almost equally originated from primary OC (POC) emissions and secondary OC (SOC) formation from fossil fuel and biomass-burning sources. In contrast, summertime OC was dominated by primary biogenic emissions as well as secondary production from biogenic and biomass burning sources, but fossil-derived SOC was the smallest contributor. Distinction of POC and SOC was performed using primary POC-to-EC emission ratios separated for fossil and nonfossil emissions. PMID- 27203473 TI - Erratum: A genome-wide association study identifies a genomic region for the polycerate phenotype in sheep (Ovis aries). PMID- 27203474 TI - April 2016 at a glance. Focus on cardiac remodeling, biomarkers and treatment. PMID- 27203475 TI - The cardiac re-AKT-ion to chronic volume overload. PMID- 27203476 TI - Natriuretic peptides and volume handling in heart failure: the paradigm of a new treatment. PMID- 27203477 TI - Empirical validation of statistical parametric mapping for group imaging of fast neural activity using electrical impedance tomography. AB - Electrical impedance tomography (EIT) allows for the reconstruction of internal conductivity from surface measurements. A change in conductivity occurs as ion channels open during neural activity, making EIT a potential tool for functional brain imaging. EIT images can have >10 000 voxels, which means statistical analysis of such images presents a substantial multiple testing problem. One way to optimally correct for these issues and still maintain the flexibility of complicated experimental designs is to use random field theory. This parametric method estimates the distribution of peaks one would expect by chance in a smooth random field of a given size. Random field theory has been used in several other neuroimaging techniques but never validated for EIT images of fast neural activity, such validation can be achieved using non-parametric techniques. Both parametric and non-parametric techniques were used to analyze a set of 22 images collected from 8 rats. Significant group activations were detected using both techniques (corrected p < 0.05). Both parametric and non-parametric analyses yielded similar results, although the latter was less conservative. These results demonstrate the first statistical analysis of such an image set and indicate that such an analysis is an approach for EIT images of neural activity. PMID- 27203478 TI - Marital status and mortality: Does family structure in childhood matter? AB - It is well known that marital status is significantly associated with mortality risk. Little is known, however, regarding whether and how the effects of marital status are moderated by one's own family structure in childhood. The purposes of this study are to examine whether marital status (i.e., family structure in adulthood) and living with both biological parents in childhood (i.e., family structure in childhood) are associated with mortality risk, and whether and how the effects of marital status vary depending on family structure in childhood and gender. We analyze the risk of death in five waves of the General Social Survey (GSS) from 1994 through 2002 after linking the GSS data to death certificate data from the National Death Index through 2008. The findings indicate that being widowed increases the risk of mortality, while living with both parents in childhood lowers it. Interestingly, analysis of the interaction between marital status and family structure in childhood reveals that the disadvantage of widowhood in terms of mortality is significantly stronger for those who lived with both parents in childhood than for those who did not. Subsample analysis by gender shows that the moderating effect of living with both parents is largely equal across men and women, though statistically more robust for men. These findings suggest that living with both parents during childhood may increase vulnerability to marital disruptions due to unwanted life events such as spousal loss. Childhood advantages, ironically, may form more stressful contexts of spousal loss by lowering one's adaptability or immunity to adulthood hardships, especially when the hardships in adulthood are characteristically opposite from the childhood advantages. PMID- 27203479 TI - Formation of Si nanowires by the electrochemical reduction of SiO2 with Ni or NiO additives. AB - Various morphologies of silicon nanowires (SiNWs) were successfully prepared by the electrochemical reduction of silica mixed with different additives (Au, Ag, Fe, Co, Ni, and NiO, respectively). Straight SiNWs were extensively obtained by the electro-reduction of porous Ni/SiO2 blocks in molten CaCl2 at 900 degrees C. The SiNWs had a wide diameter distribution of 80 to 350 nm, and the Ni-Si droplets were found on the tips of the nanowires. The growth mechanism of SiNWs was investigated, which could reveal that the nano-sized Ni-Si droplets formed at the Ni/SiO2/CaCl2 three-phase interlines. Based on the mechanism proposed, NiO particles with sub-micrometer size were selected as the additive, and straight SiNWs with diameters of 60 to 150 nm were also prepared via the electrochemical process. PMID- 27203480 TI - First Hyperpolarizability of Collagen Using the Point Dipole Approximation. AB - The application of localized hyperpolarizabilities to predict a total protein hyperpolarizability is presented for the first time, using rat-tail collagen as a demonstration example. We employ a model comprising the quadratic Applequist point-dipole approach, the so-called LoProp transformation, and a procedure with molecular fractionation using conjugate caps to determine the atomic and bond contributions to the net beta tensor of the collagen [(PPG)10]3 triple-helix. By using Tholes exponential damping modification to the dyadic tensor in the Applequist equations, a correct qualitative agreement with experiment is found. The intensity of the betaHRS signal and the depolarization ratios are best reproduced by decomposing the LoProp properties into the atomic positions and using Tholes exponential damping with the original damping parameter. Some ramifications of the model for general protein property optimization are briefly discussed. PMID- 27203481 TI - Assigning the Cerium Oxidation State for CH2CeF2 and OCeF2 Based on Multireference Wave Function Analysis. AB - The geometric and electronic structure of the recently experimentally studied molecules ZCeF2 (Z = CH2, O) was investigated by density functional theory (DFT) and wave function-based ab initio methods. Special attention was paid to the Ce-Z metal-ligand bonding, especially to the nature of the interaction between the Ce 4f and the Z 2p orbitals and the possible multiconfigurational character arising from it, as well as to the assignment of an oxidation state of Ce reflecting the electronic structure. Complete active space self-consistent field (CASSCF) calculations were performed, followed by orbital rotations in the active orbital space. The methylene compound CH2CeF2 has an open-shell singlet ground state, which is characterized by a two-configurational wave function in the basis of the strongly mixed natural CASSCF orbitals. The system can also be described in a very compact way by the dominant Ce 4f(1) C 2p(1) configuration, if nearly pure Ce 4f and C 2p orbitals are used. In the basis of these localized orbitals, the molecule is almost monoconfigurational and should be best described as a Ce(III) system. The singlet ground state of the oxygen OCeF2 complex is of closed-shell character when a monoconfigurational wave function with very strongly mixed Ce 4f and O 2p CASSCF natural orbitals is used for the description. The transformation to orbitals localized on the cerium and oxygen atoms leads to a multiconfigurational wave function and reveals characteristics of a mixed valent Ce(IV)/Ce(III) compound. Additionally, the interactions of the localized active orbitals were analyzed by evaluating the expectation values of the charge fluctuation operator and the local spin operator. The Ce 4f and C 2p orbital interaction of the CH2CeF2 compound is weakly covalent and resembles the interaction of the H 1s orbitals in a stretched hydrogen dimer. In contrast, the interaction of the localized active orbitals for OCeF2 shows ionic character. Calculated vibrational Ce-C and Ce-O stretching frequencies at the DFT, CASSCF, second-order Rayleigh-Schrodinger perturbation theory (RS2C), multireference configuration interaction (MRCI), as well as single, doubles, and perturbative triples coupled cluster (CCSD(T)) level are reported and compared to experimental infrared absorption data in a Ne and Ar matrix. PMID- 27203482 TI - A dynamic oppositional biogeography-based optimization approach for time-varying electrical impedance tomography. AB - Dynamic electrical impedance tomography-based image reconstruction using conventional algorithms such as the extended Kalman filter often exhibits inferior performance due to the presence of measurement noise, the inherent ill posed nature of the problem and its critical dependence on the selection of the initial guess as well as the state evolution model. Moreover, many of these conventional algorithms require the calculation of a Jacobian matrix. This paper proposes a dynamic oppositional biogeography-based optimization (OBBO) technique to estimate the shape, size and location of the non-stationary region boundaries, expressed as coefficients of truncated Fourier series, inside an object domain using electrical impedance tomography. The conductivity of the object domain is assumed to be known a priori. Dynamic OBBO is a novel addition to the family of dynamic evolutionary algorithms. Moreover, it is the first such study on the application of dynamic evolutionary algorithms for dynamic electrical impedance tomography-based image reconstruction. The performance of the algorithm is tested through numerical simulations and experimental study and is compared with state of-the-art gradient-based extended Kalman filter. The dynamic OBBO is shown to be far superior compared to the extended Kalman filter. It is found to be robust to measurement noise as well as the initial guess, and does not rely on a priori knowledge of the state evolution model. PMID- 27203483 TI - Emergency Physicians' Experience with Advance Care Planning Documentation in the Electronic Medical Record: Useful, Needed, and Elusive. AB - OBJECTIVE: For patients' preferences to be honored, emergency department (ED) physicians must be able to find and use advance care planning (ACP) information in the electronic medical record (EMR). ED physicians' experiences with ACP EMR documentation and their documentation needs are unknown. METHODS: We surveyed 70 ED physicians (81% response rate) from a tertiary and county ED. Our primary outcome was confidence finding and using ACP EMR documentation (percentage reporting very/extremely on a five-point Likert scale). Secondary outcomes included frequency of use and perceived usefulness of types of ACP documentation. Suggestions for improvement were analyzed using thematic content analysis. RESULTS: Participants' mean age was 36 years (+/- 9) and 54% were women. Thirty one percent reported being very/extremely confident they could find ACP EMR documentation, and 55% felt very/extremely confident they could use it to care for patients. Yet 74% needed it >=1 time/week and 43% >=5 times/week. Participants reported code status orders (90%), Physician Orders for Life Sustaining Treatment (POLST) (86%), and durable power of attorney for health care (78%) as very/extremely useful, followed by values statements (31%), oral directives (34%), and living wills (37%). ED physicians wanted highly visible ACP information, "on the main screen." CONCLUSIONS: EMR systems are not optimized to provide critical ACP information to ED physicians who lack confidence finding or using ACP EMR documentation to care for patients. Dedicated ACP information on the EMR home screen and tailored training may be needed to help ED providers find, use, and discuss ACP documentation to provide care aligned with patients' goals. PMID- 27203484 TI - The lung: a magnificent organ that needs lifelong attention. PMID- 27203485 TI - The next Director-General of WHO. PMID- 27203486 TI - Transforming primary care. PMID- 27203487 TI - Vilanterol fluticasone and mortality in comorbid COPD GOLD B. PMID- 27203488 TI - Expanding the benefits of HPV vaccination to boys and men. PMID- 27203490 TI - US responds to increase in Zika cases. PMID- 27203491 TI - The age of drones: what might it mean for health? PMID- 27203494 TI - Maria Neira: no limits to public health. PMID- 27203495 TI - The medicine of Alex Higgins. PMID- 27203496 TI - Holbrook Kohrt. PMID- 27203497 TI - No universal health coverage without primary health care. PMID- 27203498 TI - Uncommon presentation of Zika fever or co-infection? PMID- 27203499 TI - Uncommon presentation of Zika fever or co-infection? - Authors' reply. PMID- 27203500 TI - Suicide in adolescent girls - Authors' reply. PMID- 27203501 TI - Suicide in adolescent girls. PMID- 27203502 TI - Do generic correction algorithms produce reliable estimates? PMID- 27203504 TI - Department of Error. PMID- 27203503 TI - The urgency of a sociocultural approach to adolescent men's health risk behaviours. PMID- 27203505 TI - Department of Error. PMID- 27203506 TI - Department of Error. PMID- 27203507 TI - Clarification regarding ethical review of Paolo Macchiarini's research. PMID- 27203509 TI - Clinical challenges in mechanical ventilation. AB - Mechanical ventilation supports gas exchange and alleviates the work of breathing when the respiratory muscles are overwhelmed by an acute pulmonary or systemic insult. Although mechanical ventilation is not generally considered a treatment for acute respiratory failure per se, ventilator management warrants close attention because inappropriate ventilation can result in injury to the lungs or respiratory muscles and worsen morbidity and mortality. Key clinical challenges include averting intubation in patients with respiratory failure with non invasive techniques for respiratory support; delivering lung-protective ventilation to prevent ventilator-induced lung injury; maintaining adequate gas exchange in severely hypoxaemic patients; avoiding the development of ventilator induced diaphragm dysfunction; and diagnosing and treating the many pathophysiological mechanisms that impair liberation from mechanical ventilation. Personalisation of mechanical ventilation based on individual physiological characteristics and responses to therapy can further improve outcomes. PMID- 27203508 TI - Fluticasone furoate and vilanterol and survival in chronic obstructive pulmonary disease with heightened cardiovascular risk (SUMMIT): a double-blind randomised controlled trial. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) often coexists with cardiovascular disease. Treatments for airflow limitation might improve survival and both respiratory and cardiovascular outcomes. The aim of this study was to assess whether inhaled treatment with a combined treatment of the corticosteroid, fluticasone furoate, and the long-acting beta agonist, vilanterol could improve survival compared with placebo in patients with moderate COPD and heightened cardiovascular risk. METHODS: In this double-blind randomised controlled trial (SUMMIT) done in 1368 centres in 43 countries, eligible patients were aged 40-80 years and had a post-bronchodilator forced expiratory volume in 1 s (FEV1) between 50% and 70% of the predicted value, a ratio of post-bronchodilator FEV1 to forced vital capacity (FVC) of 0.70 or less, a smoking history of at least 10 pack-years, and a score of 2 or greater on the modified Medical Research Council dyspnoea scale. Patients had to have a history, or be at increased risk, of cardiovascular disease. Enrolled patients were randomly assigned (1:1:1:1) through a centralised randomisation service in permuted blocks to receive once daily inhaled placebo, fluticasone furoate (100 MUg), vilanterol (25 MUg), or the combination of fluticasone furoate (100 MUg) and vilanterol (25 MUg). The primary outcome was all-cause mortality, and secondary outcomes were on-treatment rate of decline in forced expiratory volume in 1 s (FEV1) and a composite of cardiovascular events. Safety analyses were performed on the safety population (all patients who took at least one dose of study drug) and efficacy analyses were performed on the intention-to-treat population (safety population minus sites excluded with Good Clinical Practice violations). This study is registered with ClinicalTrials.gov, number NCT01313676. FINDINGS: Between Jan 24, 2011, and March 12, 2014, 23 835 patients were screened, of whom 16 590 were randomised. 16 485 patients were included in the intention-to-treat efficacy population; 4111 in the placebo group, 4135 in the fluticasone furoate group, 4118 in the vilanterol group, and 4121 in the combination group. Compared with placebo, all-cause mortality was unaffected by combination therapy (hazard ratio [HR] 0.88 [95% CI 0.74-1.04]; 12% relative reduction; p=0.137) or the components (fluticasone furoate, HR 0.91 [0.77-1.08]; p=0.284; vilanterol, 0.96 [0.81-1.14]; p=0.655), and therefore secondary outcomes should be interpreted with caution. Rate of decline in FEV1 was reduced by combination therapy (38 mL per year [SE 2.4] vs 46 mL per year [2.5] for placebo, difference 8 mL per year [95% CI 1-15]) with similar findings for fluticasone furoate (difference 8 mL per year [95% CI 1 14]), but not vilanterol (difference -2 mL per year [95% CI -8 to 5]). Combination therapy had no effect on composite cardiovascular events (HR 0.93 [95% CI 0.75-1.14]) with similar findings for fluticasone furoate (0.90 [0.72 1.11]) and vilanterol (0.99 [0.80-1.22]). All treatments reduced the rate of moderate and severe exacerbation. No reported excess risks of pneumonia (5% in the placebo group, 6% in the combination group, 5% in the fluticasone furoate group, and 4% in the vilanterol group) or adverse cardiac events (17% in the placebo group, 18% in the combination group, and 17% in the fluticasone furoate group, and 17% in the vilanterol group) were noted in the treatment groups. INTERPRETATION: In patients with moderate COPD and heightened cardiovascular risk, treatment with fluticasone furoate and vilanterol did not affect mortality or cardiovascular outcomes, reduced exacerbations, and was well tolerated. Fluticasone furoate, alone or in combination with vilanterol, seemed to reduce FEV1 decline. FUNDING: GlaxoSmithKline. PMID- 27203510 TI - High-flow oxygen therapy and other inhaled therapies in intensive care units. AB - In this Series paper, we review the current evidence for the use of high-flow oxygen therapy, inhaled gases, and aerosols in the care of critically ill patients. The available evidence supports the use of high-flow nasal cannulae for selected patients with acute hypoxaemic respiratory failure. Heliox might prevent intubation or improve gas flow in mechanically ventilated patients with severe asthma. Additionally, it might improve the delivery of aerosolised bronchodilators in obstructive lung disease in general. Inhaled nitric oxide might improve outcomes in a subset of patients with postoperative pulmonary hypertension who had cardiac surgery; however, it has not been shown to provide long-term benefit in patients with acute respiratory distress syndrome (ARDS). Inhaled prostacyclins, similar to inhaled nitric oxide, are not recommended for routine use in patients with ARDS, but can be used to improve oxygenation in patients who are not adequately stabilised with traditional therapies. Aerosolised bronchodilators are useful in mechanically ventilated patients with asthma and chronic obstructive pulmonary disease, but are not recommended for those with ARDS. Use of aerosolised antibiotics for ventilator-associated pneumonia and ventilator-associated tracheobronchitis shows promise, but the delivered dose can be highly variable if proper attention is not paid to the delivery method. PMID- 27203511 TI - Comparisons of patients' satisfaction should take expectations into account. PMID- 27203513 TI - Amine Gradient Stationary Phases on In-House Built Monolithic Columns for Liquid Chromatography. AB - Stationary phase gradients on monolithic silica columns have been successfully and reproducibly prepared and characterized with comparisons made to uniformly modified stationary phases. Stationary phase gradients hold great potential for use in liquid chromatography (LC), both in terms of simplifying analysis as well as providing novel selectivity. In this work, we demonstrate the creation of a continuous stationary phase gradient on in-house synthesized monolithic columns by infusing an aminoalkoxysilane solution through the silica monoliths via controlled rate infusion. The presence of amine and its distribution along the length of gradient and uniformly modified columns were assessed via X-ray photoelectron spectroscopy (XPS). XPS showed a clear gradient in surface coverage along the length of the column for the gradient stationary phases while a near uniform distribution on the uniformly modified stationary phases. To demonstrate the application of these gradient stationary phases, the separations of both nucleobases and weak acids/weak bases on these gradient stationary phases have been compared to uniformly modified and unmodified silica columns. Of particular note, the retention characteristics of 11 gradient columns, 5 uniformly modified columns, and 5 unmodified columns have been tested to establish the reproducibility of the synthetic procedures. Standard deviations of the retention factors were in the range from 0.06 to 0.5, depending on the analyte species. We show that selectivity is achieved with the stationary phase gradients that are significantly different from either uniformly modified amine or unmodified columns. These results indicate the significant promise of this strategy for creating novel stationary phases for LC. PMID- 27203512 TI - Unambiguous Identification of beta-Tubulin as the Direct Cellular Target Responsible for the Cytotoxicity of Chalcone by Photoaffinity Labeling. AB - Chalcone is a simple and potentially privileged structure in medicinal chemistry with a diverse repertoire of biological activities, among which cytotoxicity is of particular interest. The sharp structure-activity relationship (SAR) for chalcone's cytotoxicity suggests structure-specific target interactions. Despite the numerous putative targets proposed, evidence for direct target interactions in cells is unavailable. In this study, guided by the sharp cytotoxic SAR, we developed a cytotoxic chalcone-based photoaffinity labeling (PAL) probe, (E)-3-(3 azidophenyl)-1-[3,5-dimethoxy-4-(prop-2-yn-1-yloxy)phenyl]-2-methylprop-2-en-1 one (C95; IC50 : 0.38+/-0.01 MUm), along with two structurally similar non cytotoxic probes. These probes were used to search for the direct cellular target responsible for chalcone's cytotoxicity through intact cell-based PAL experiments, in which beta-tubulin was identified to specifically interact with the cytotoxic probe (i.e., C95) but not the non-cytotoxic probes. A set of phenotypical and biochemical assays further reinforced beta-tubulin as the cytotoxic target of chalcones. Peptide mass quantitation by mass spectrometric analysis revealed one peptide potentially labeled by C95, providing information on chalcone's binding site on beta-tubulin. PMID- 27203514 TI - Does being overweight or male increase a patient's risk of not being referred for an eating disorder consult? AB - OBJECTIVE: To examine whether sex, age, body mass index (BMI), and eating disorder diagnosis were associated with referral rates for eating disorder consults in a general inpatient psychiatric facility. METHOD: An inpatient sample of 136 individuals with a current eating disorder diagnosis were utilized for this study. Chi square and logistic regression were used to identify variables affecting the likelihood of having an eating disorder consult. RESULTS: More women than men were identified as having a current eating disorder diagnosis. For both women and men, eating disorder not otherwise specified (EDNOS) was the most common diagnosis, followed by binge-eating disorder (BED). Compared to women, there were more men who did not receive an eating disorder consult. Specifically, overweight men were less likely to be referred for a consult. DISCUSSION: Results highlight the need of healthcare providers to ask all individuals about their eating habits, which could then provide an opportunity to explore eating disorder symptoms. Due to historical biases, the less distinct nature of some diagnoses or the absence of symptoms that have been considered indicators of clinical severity, providers may be more likely to overlook individuals with diagnoses of EDNOS and BED for consults, especially men. (c) 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:963-966). PMID- 27203515 TI - Safety and Efficacy of GreenLight XPS Laser Vapoenucleation in Prostates Measuring Over 150 mL. AB - INTRODUCTION: The GreenLightTM XPS Laser System (GL-XPS) is a safe and efficacious treatment for lower urinary tract symptoms due to benign prostatic hyperplasia (BPH), but there is limited evidence on its use in prostates over 150 mL. We demonstrate the safety and efficacy of the GL-XPS system using a vapoenucleation technique in prostate glands measuring over 150 mL. METHODS: We prospectively collected data on all consecutive patients with prostates measuring over 150 mL on transrectal ultrasound treated with the GL-XPS (AMS, Inc., Minnetonka, MN) at a tertiary referral center from September 2011 to October 2015. Data collected include prostate volume, International Prostate Symptom Score (IPSS) and quality of life (QoL) scores, maximum urinary flow rate (Qmax), postvoid residual (PVR), prostate-specific antigen, complications, and reintervention rates. RESULTS: Seventy male patients with a median prostate size of 202 mL (range 152-376 mL) were included. There were 41 patients (59%) in preoperative urinary retention with an indwelling catheter preoperatively. Thirty seven (53%) patients were American Society of Anesthesiologists (ASA) class 2 and 33 (47%) were class 3. Median operative time was 180 minutes, laser time 97 minutes, energy utilization 674 kJ, and energy density 3.3 kJ/mL, with median 3 fibers used per case. Median length of stay and length of catheterization were 1 day. IPSS and QoL scores demonstrated significant improvements from baseline at all endpoints, improving from 16 to 3.5 and from 4 to 1 at 24 months, respectively (p = 0.001). At 12 months, Qmax and PVR improved from 10.1 to 22.4 mL/s (p = 0.043) and from 84 to 31.4 mL (p = 0.015), respectively. Retreatment was required in two patients (2.9%). CONCLUSION: GL-XPS vapoenucleation provided durable subjective and objective improvements in symptoms and voiding parameters, with no serious adverse events in men with prostates >150 mL. PMID- 27203516 TI - Exogenous cofactors for the improvement of bioremoval and biotransformation of sulfamethoxazole by Alcaligenes faecalis. AB - Sulfamethoxazole (SMX), an extensively prescribed or administered antibiotic pharmaceutical product, is usually detected in aquatic environments, because of its incomplete metabolism and elimination. This study investigated the effects of exogenous cofactors on the bioremoval and biotransformation of SMX by Alcaligenes faecalis. High concentration (100mg.L(-1)) of exogenous vitamin C (VC), vitamin B6 (VB6) and oxidized glutathione (GSSG) enhanced SMX bioremoval, while the additions of vitamin B2 (VB2) and vitamin B12 (VB12) did not significantly alter the SMX removal efficiency. Globally, cellular growth of A. faecalis and SMX removal both initially increased and then gradually decreased, indicating that SMX bioremoval is likely dependent on the primary biomass activity of A. faecalis. The decreases in the SMX removal efficiency indicated that some metabolites of SMX might be transformed into parent compound at the last stage of incubation. Two transformation products of SMX, N-hydroxy sulfamethoxazole (HO SMX) and N4-acetyl sulfamethoxazole (Ac-SMX), were identified by a high performance liquid chromatograph coupled with mass spectrometer. High concentrations of VC, nicotinamide adenine dinucleotide hydrogen (NADH, 7.1mg.L( 1)), and nicotinamide adenine dinucleotide (NAD(+), 6.6mg.L(-1)), and low concentrations of reduced glutathione (GSH, 0.1 and 10mg.L(-1)) and VB2 (1mg.L( 1)) remarkably increased the formation of HO-SMX, while VB12 showed opposite effects on HO-SMX formation. In addition, low concentrations of GSH and NADH enhanced Ac-SMX formation by the addition of A. faecalis, whereas cofactors (VC, VB2, VB12, NAD(+), and GSSG) had no obvious impact on the formation of Ac-SMX compared with the controls. The levels of Ac-SMX were stable when biomass of A. faecalis gradually decreased, indicating the direct effect of biomass on the formation of Ac-SMX by A. faecalis. In sum, these results help us understand the roles played by exogenous cofactors in eliminating SMX by A. faecalis and provide potential strategies for improving SMX biodegradation. PMID- 27203517 TI - Effect of inter-annual variability in pasture growth and irrigation response on farm productivity and profitability based on biophysical and farm systems modelling. AB - Farm system and nutrient budget models are increasingly being used in analysis to inform on farm decision making and evaluate land use policy options at regional scales. These analyses are generally based on the use of average annual pasture yields. In New Zealand (NZ), like in many countries, there is considerable inter annual variation in pasture growth rates, due to climate. In this study a modelling approach was used to (i) include inter-annual variability as an integral part of the analysis and (ii) test the approach in an economic analysis of irrigation in a case study within the Hawkes Bay Region of New Zealand. The Agricultural Production Systems Simulator (APSIM) was used to generate pasture dry matter yields (DMY) for 20 different years and under both dryland and irrigation. The generated DMY were linked to outputs from farm-scale modelling for both Sheep and Beef Systems (Farmaxx Pro) and Dairy Systems (Farmax(r) Dairy Pro) to calculate farm production over 20 different years. Variation in DMY and associated livestock production due to inter-annual variation in climate was large, with a coefficient of variations up to 20%. Irrigation decreased this inter-annual variation. On average irrigation, with unlimited available water, increased income by $831 to 1195/ha, but when irrigation was limited to 250mm/ha/year income only increased by $525 to 883/ha. Using pasture responses in individual years to capturing the inter-annual variation, rather than the pasture response averaged over 20years resulted in lower financial benefits. In the case study income from irrigation based on an average year were 10 to >20% higher compared with those obtained from individual years. PMID- 27203518 TI - Environmental impact of heavy pig production in a sample of Italian farms. A cradle to farm-gate analysis. AB - Four breeding piggeries and eight growing-fattening piggeries were analyzed to estimate potential environmental impacts of heavy pig production (>160kg of live height at slaughtering). Life Cycle Assessment methodology was adopted in the study, considering a system from breeding phase to growing fattening phase. Environmental impacts of breeding phase and growing-fattening phase were accounted separately and then combined to obtain the impacts of heavy pig production. The functional unit was 1kg of live weight gain. Impact categories investigated were global warming (GW), acidification (AC), eutrophication (EU), abiotic depletion (AD), and photochemical ozone formation (PO). The total environmental impact of 1kg of live weight gain was 3.3kg CO2eq, 4.9E-2kg SO2eq, 3.1E-2kg PO4(3-)eq, 3.7E-3kg Sbeq, 1.7E-3kg C2H4eq for GW, AC, EU, AD, and PO respectively. Feed production was the main hotspot in all impact categories. Greenhouse gases responsible for GW were mainly CH4, N2O, and CO2. Ammonia was the most important source of AC, sharing about 90%. Nitrate and NH3 were the main emissions responsible for EU, whereas P and NOx showed minor contributions. Crude oil and natural gas consumption was the main source of AD. A large spectrum of pollutants had a significant impact on PO: they comprised CH4 from manure fermentation, CO2 caused by fossil fuel combustion in agricultural operations and industrial processes, ethane and propene emitted during oil extraction and refining, and hexane used in soybean oil extraction. The farm characteristics that best explained the results were fundamentally connected with performance indicators Farms showed a wide variability of results, meaning that there was wide margin for improving the environmental performance of either breeding or growing-fattening farms. The effectiveness of some mitigation measures was evaluated and the results that could be obtained by their introduction have been presented. PMID- 27203519 TI - Growth under elevated air temperature alters secondary metabolites in Robinia pseudoacacia L. seedlings in Cd- and Pb-contaminated soils. AB - Plant secondary metabolites play a pivotal role in growth regulation, antioxidant activity, pigment development, and other processes. As the global climate changes, increasing atmospheric temperatures and contamination of soil by heavy metals co-occur in natural ecosystems, which alters the pH of rhizosphere soil and influences the bioavailability and mobility of metals. Elevated temperatures in combination with heavy metals are expected to affect plant secondary metabolites, but this issue has not been extensively examined. Here, we investigated secondary metabolites in Robiniapseudoacacia seedlings exposed to elevated temperatures using a passive warming device in combination with Cd- and Pb-contaminated soils. Heavy metals significantly stimulated the accumulation of saponins, phenolic compounds, and flavonoids in leaves and stems; alkaloid compounds increased in leaves and decreased in stems, and condensed tannins fluctuated. Elevated temperatures, alone and in combination with Cd and Pb, caused increases in secondary metabolites in the plant tissues. Phenolic compounds showed the greatest changes among the secondary metabolites and significant interactive effects of temperature and metals were observed. These results suggest that slightly elevated temperature could enhance protective and defense mechanisms of Robinia pseudoacacia seedlings exposed to heavy metals by stimulating the production of secondary metabolites. PMID- 27203520 TI - A review of the measurement procedure of the ISO 1996 standard. Relationship with the European Noise Directive. PMID- 27203521 TI - A land use regression application into assessing spatial variation of intra-urban fine particulate matter (PM2.5) and nitrogen dioxide (NO2) concentrations in City of Shanghai, China. AB - Intra-urban assessment of air pollution exposure has become a priority study while international attention was attracted to PM2.5 pollution in China in recent years. Land Use Regression (LUR), which has previously been proved to be a feasible way to describe the relationship between land use and air pollution level in European and American cities, was employed in this paper to explain the correlations and spatial variations in Shanghai, China. PM2.5 and NO2 concentrations at 35-45 monitoring locations were selected as dependent variables, and a total of 44 built environmental factors were extracted as independent variables. Only five factors showed significant explanatory value for both PM2.5 and NO2 models: longitude, distance from monitors to the ocean, highway intensity, waterbody area, and industrial land area for PM2.5 model; residential area, distance to the coast, industrial area, urban district, and highway intensity for NO2 model. Respectively, both PM2.5 and NO2 showed anti correlation with coastal proximity (an indicator of clean air dilution) and correlation with highway and industrial intensity (source indicators). NO2 also showed significant correlation with local indicators of population density (residential intensity and urban classification), while PM2.5 showed significant correlation with regional dilution (longitude as a indicator of distance from polluted neighbors and local water features). Both adjusted R squared values were strong with PM2.5 (0.88) being higher than NO2 (0.62). The LUR was then used to produce continuous concentration fields for NO2 and PM2.5 to illustrate the features and, potentially, for use by future studies. Comparison to PM2.5 studies in New York and Beijing show that Shanghai PM2.5 pollutant distribution was more sensitive to geographic location and proximity to neighboring regions. PMID- 27203522 TI - Reducing natural organic matter and disinfection by-product precursors by alternating oxic and anoxic conditions during engineered short residence time riverbank filtration: A laboratory-scale column study. AB - Riverbank filtration (RBF) with days to months of residence time has been successfully used as treatment or pre-treatment process to improve water quality for decades. However, its feasibility depends on the local hydrogeological conditions. Therefore, for sites unsuitable to traditional RBF, a smaller engineered RBF may be an option. This study evaluates the performance of engineered short residence time RBF on improving water quality, focusing on the removal of natural organic matter (NOM) and the reduction of precursors of carbon and nitrogen disinfection by-products (DBP). Lab-scale experiments were conducted with surface feed water from a drinking water plant. The results showed that within 6days hydraulic retention time (HRT), 60-70% dissolved organic carbon (DOC) and 70-80% ultraviolet absorbance at 254nm (UV254) could be removed. During the whole filtration process, biodegradation was responsible for the removal of organic matter, and it was found that alternating redox condition between oxic and anoxic was beneficial for the overall performance of the RBF. Dissolved oxygen (DO) had a substantial impact on the removal of DBP precursors. For carbon containing DBP (C-DBP) precursors' removal, re-aeration after a sequence of oxic and anoxic conditions could further increase the removal efficiencies from 50%, 60%, and 60% to 80%, 90%, and 80% for trihalomethanes (THMs), chloral hydrate (CH), and haloketones (HKs). Prolonged anoxic conditions were however beneficial for the removal of nitrogen-containing DBP (N-DBP) precursors. PMID- 27203523 TI - Seasonal and annual variations in physiological and biochemical responses from transplanted marine bioindicator species Mytilus spp. during a long term field exposure experiment. AB - In a pilot field study the long term response of transplanted bioindicator organisms Mytilus spp. was analyzed on the basis of physiological indices and biochemical measurements related to the energy budget. Three different time series with deployment times of eight to twelve months were compared according to seasonality and repeatability of the responses. Test organisms were incubated at a coastal station in the anthropogenically impacted estuary of the river Elbe and at a North Sea station located in vicinity to the Island of Helgoland in the German Bight. The stations differ in their hydrological as well as chemical characteristics. They can be discriminated by statistical factor analysis based on the measured biochemical parameter. Levels of all energy budget biomarker varied between seasons; however, the degree of variation of the specific response was differently expressed. The mussels deployed at Helgoland showed a reproducible high Condition Index in each sampling series and an oscillating Gonadosomatic Index representing the reproduction cycle. The lowest available energy was recorded in mussels at the estuarine sampling station compared to the off-shore station. This may be caused by the energetically costly maintenance of osmotic balance and consequently result in a lower amount of energy available for defense again chemical stress, growth and reproduction. PMID- 27203524 TI - Effect of pycnogenol and spirulina on vancomycin-induced renal cortical oxidative stress, apoptosis, and autophagy in adult male albino rat. AB - Vancomycin-induced nephrotoxicity has been reported to occur in 5%-25% of patients who were administered with it. Several natural antioxidants were found to be effective against drug-induced toxicity. We evaluated the possible protective effects of spirulina and pycnogenol alone or in combination on vancomycin-induced renal cortical oxidative stress. Forty-nine rats were randomly divided into 7 groups: group I, control; group II, received spirulina 1000 mg/kg per day; group III, received pycnogenol 200 mg/kg per day; group IV, received vancomycin 200 mg/kg per day every 12 h; group V, (spirulina + vancomycin); group VI, (pycnogenol + vancomycin); and group VII, (pycnogenol + spirulina + vancomycin). At the end of the experiment, kidney functions were estimated and then the kidneys were removed, weighed, and sampled for histopathological, immunohistochemistry, and biochemical studies. Administration of spirulina and pycnogenol alone or in combination decreased elevated serum creatinine, blood urea nitrogen, renal malondialdehyde, and immunoexpression of the proapoptotic protein (Bax), autophagic marker protein (LC3/B), and inducible nitric oxide synthase induced by vancomycin. They increased reduced glutathione, glutathione peroxidase, superoxide dismutase, and immunoexpression of the antiapoptotic protein (Bcl2). They also ameliorated the morphological changes induced by vancomycin. The combination therapy of spirulina and pycnogenol showed better protective effects than the corresponding monotherapy. PMID- 27203525 TI - The polyvinylpyrrolidone functionalized rGO/Bi2S3 nanocomposite as a near infrared light-responsive nanovehicle for chemo-photothermal therapy of cancer. AB - Recently, a combination of chemotherapy with photothermal therapy (PTT) has received great attention for the construction of a near infrared (NIR)-controlled drug-delivery system for synergistic treatment of cancer, ultimately resulting in the enhancement of the therapeutic efficacy of anticancer drugs. Here, we developed a novel system for synergistic cancer therapy based on bismuth sulfide (Bi2S3) nanoparticle-decorated graphene functionalized with polyvinylpyrrolidone (PVP) (named PVP-rGO/Bi2S3). The as-prepared PVP-rGO/Bi2S3 nanocomposite has a high storage capacity for anticancer drugs (~500% for doxorubicin (DOX)) and simultaneously has perfect photothermal conversion efficiency in the NIR region. The results of the in vitro accumulative drug release test manifests that the PVP rGO/Bi2S3 nanocomposite could be applied as a dual pH- and NIR-responsive nanotherapeutic carrier for the controlled release of DOX from DOX-loaded PVP rGO/Bi2S3 (PVP-rGO/Bi2S3@DOX). Moreover, the treatment of both cancer cells (including Hela, MCF-7, HepG2 and BEL-7402 cells) and BEL-7402 tumor-bearing mice with the PVP-rGO/Bi2S3@DOX complex followed by NIR laser irradiation produces significantly greater inhibition of cancer cell growth than the treatment with NIR irradiation alone or DOX alone, exhibiting a synergistic antitumor effect. Furthermore, due to the obvious NIR and X-ray absorption ability, the PVP rGO/Bi2S3 nanocomposite could be employed as a dual-modal contrast agent for both photoacoustic tomography and X-ray computed tomography imaging. In addition to the good biocompatibility, the PVP-rGO/Bi2S3 nanocomposite paves a potential way for the fabrication of theranostic agents for dual-modal imaging-guided chemo photothermal combined cancer therapy. PMID- 27203526 TI - A tristable [2]rotaxane that is doubly gated by foldamer and azobenzene kinetic barriers. AB - A hydrogen bonded foldamer unit and an azobenzene unit have been incorporated into the linear component of a tristable [2]rotaxane to give rise to a doubly gated switching system tuned by the folding-defolding of the foldamer unit and the photo-initiated trans-cis isomerization of the azobenzene unit. PMID- 27203527 TI - Predominance of Three Closely Related Methicillin-Resistant Staphylococcus aureus Clones Carrying a Unique ccrC-Positive SCCmec type III and the Emergence of spa t304 and t690 SCCmec type IV pvl+ MRSA Isolates in Kinta Valley, Malaysia. AB - We investigated the epidemiology and clonality of 175 nonrepetitive methicillin resistant Staphylococcus aureus (MRSA) isolates from clinical specimens collected between 2011 and 2012 in Kinta Valley in Malaysia. Molecular tools such as polymerase chain reaction, pulsed-field gel electrophoresis, and staphylococcal protein A (spa) typing were used. Our study revealed the predominance of three closely related ermA+ SCCmec type III pulsotypes belonging to spa type t037 (Brazilian-Hungarian clone), which were deficient in the locus F, but positive for the ccrC gene in majority (65.7%) of the MRSA infections in this region. The first evidence of SCCmec type II MRSA in the country, belonging to spa type t2460, was also noted. Although the carriage of pvl gene was uncommon (8.6%) and mostly confined to either SCCmec type IV or SCCmec type V isolates, most of these isolates belonged to spa types t345 or t657, which are associated with the Bengal Bay CA-MRSA clone. Interestingly, spa t304 and t690 SCCmec type IV pvl+ were also detected among the MRSA isolates. Data from this study show the rise of uncommon clones among MRSA isolates in Malaysia. PMID- 27203528 TI - Tandem Catalysis Utilizing Olefin Metathesis Reactions. AB - Since olefin metathesis transformation has become a favored synthetic tool in organic synthesis, more and more distinct non-metathetical reactions of alkylidene ruthenium complexes have been developed. Depending on the conditions applied, the same olefin metathesis catalysts can efficiently promote isomerization reactions, hydrogenation of C=C double bonds, oxidation reactions, and many others. Importantly, these transformations can be carried out in tandem with olefin metathesis reactions. Through addition of one portion of a catalyst, a tandem process provides structurally advanced products from relatively simple substrates without the need for isolation of the intermediates. These aspects not only make tandem catalysis very attractive from a practical point of view, but also open new avenues in (retro)synthetic planning. However, in the literature, the term "tandem process" is sometimes used improperly to describe other types of multi-reaction sequences. In this Concept, a number of examples of tandem catalysis involving olefin metathesis are discussed with an emphasis on their synthetic value. PMID- 27203529 TI - [In Process Citation]. PMID- 27203530 TI - [Psychotherapy: Legally recognized in Quebec]. AB - Until recently, Quebec was the first to have regulated the practice of psychotherapy through law adopted in 2009. The law emerged following 30 years of efforts and inter-professional discussions that led to a consensus by an expert committee presided by Dr Jean-Bernard Trudeau in 2005. In this essay, Dr Jean Bernard Trudeau, general practitioner, and two psychiatrist and psychologist colleagues, who have participated to the expert committee or have been involved more recently in the implementation of law no 21 in Quebec, relate the main landmarks and moments in the regulation of the practice in psychotherapy following this inter-professional consensus that was translated in the law 21. They relate particularly the last ten years that have led to the adoption of law 21 in 2009, following two parliamentary commission after the Trudeau report. They underline how the practice of psychotherapy is integrated in the professional system and submitted to strict regulation. It includes regulations for obtaining the license of psychotherapist and for maintaining competence. Guidelines emerging from continuous inter-professional discussions for the application of the law and of its regulation in the public and private sectors are produced by the Quebec Professions Office. The definition of psychotherapy that was reached by consensus is not limited to the treatment of mental disorders and is distinguished from other intervention in the area of human relations. Continuous training is mandatory and is implemented on one hand by the Order of the psychologists for the psychologists and other professionals practicing psychotherapy and on the other hand the College of physicians for physician practicing psychotherapy. The authors finally described the interdisciplinary advisory council for the practice of psychotherapy that the legislator has foreseen as an external mechanism to insure the conformity of regulation with the spirit of the law and to give opinions to the various professional orders. PMID- 27203531 TI - [The Practice Directorate of the Canadian Psychological Association: Psychology advocacy across Canada]. AB - Increasing access to psychological services across Canada has long been a focus of national and provincial/territorial psychology advocacy bodies. The Practice Directorate (PD) of the Canadian Psychological Association (CPA) is comprised of representatives from each of the advocacy psychology associations and a representative from CPA. Its mandate is to increase the efficiency and effectiveness of psychology advocacy by sharing information and collaborating on initiatives across Canadian jurisdictions. This commentary highlights past, present, and future initiatives of the PD through policy statements, campaigns, public education, surveys, and training opportunities aimed at supporting advocacy in increasing access to psychological services for all Canadians. PMID- 27203532 TI - [Psychological Psychotherapy in Switzerland: Moving towards Transparency and Quality]. AB - The article gives an overview of psychological psychotherapy in Switzerland. We describe the legal status of psychological psychotherapists, their position and role within the Swiss health-care system, the professional context they practice in, the format of psychotherapy training, various employment models of psychological psychotherapists, as well as the currently insufficient reimbursement situation of psychological psychotherapy. Reimbursement by mandatory health insurance is highlighted as the most important current challenge psychological psychotherapists face in Switzerland, on their way to be fully acknowledged as independent providers of psychotherapy. PMID- 27203533 TI - [Collaboration between Medicine and Psychology: Evolving Mentalities in Belgium and Evolution of the Health Care System in Canada]. AB - Objectives 1) To give a portrait of the evolving mentalities prevailing in Belgium on the collaboration between psychologists and general practitioners, and identify the barriers to the development of the collaboration between those two health professionals 2) To report on the primary care reform in Canada, its role in fostering collaborative practice in primary mental health and on the strategies needed to improve collaboration.Methods Literature search using PubMed and Google Scholar.Results Because of the unmet need of psychologists in primary care, general practitioners and psychologists have a propensity to work together. However to facilitate the collaborative process there needs to be system changes and clear definition of scopes of practices. Both countries are at different levels of implementing change. In Belgium for example it is only very recently that the autonomous practice of clinical psychology has been acknowledged. In Canada although the primary care reform has put forward and supported collaborative care, focus on mental health is insufficient. Early reports on collaborative care in the new models of care inconsistently report improved health outcomes. Strategies to improve collaborative care are looking at teaching future health professionals on how to work together by integrating inter professional education.Conclusion Both the health care system and graduate training need to support foster and teach collaborative care. PMID- 27203534 TI - [Advocating for the Inclusion of Psychologists in Family Health Teams in Ontario, Canada]. AB - Objectives This article advocates in favor of increasing the accessibility of psychological services in primary health care by focusing more specifically on the relevance of including psychologists in family health teams in primary care in Ontario.Methods The authors present their advocacy from two levels of information: 1) the main results of a demonstration project funded by the Primary Health Care Transition Fund (PHCTF) in which psychologists were integrated into family practices; and 2) experiences and general observations drawn from the combined experiences of the authors from the last decade regarding the inclusion of psychologists in primary care.Results Main results from the demonstration project: 1) highly prevalent mental illnesses (anxiety & mood disorders) are amenable to psychological interventions; 2) psychologists and family physicians are natural and complementary allies in primary care; 3) the cost of integrating psychologists to provide psychological interventions can be off-set by a reduction in physicians' mental health billing. Main observations drawn from authors' combined experiences in primary care: 1) relatively few psychologists work in family health teams in Ontario; 2) most non-pharmacological mental health interventions in primary care involve generic counselling, problem solving, educational groups, and linking to community resources; 3) lack of understanding of the difference between evidence-based psychological treatments and generic counselling; 4) many multidisciplinary clinics unfortunately benefit from only one type of non-medical mental health professional as part of their team to see all cases, independent of the level of complexity on the patient's side, and independent of the level of expertise or supervised training on the provider side; 5) multidisciplinary teams in primary care need various mental health professionals to cover for a wide range of presenting problems and levels of complexity/co-morbidities.Conclusion Our demonstration project combined with our continued clinical experience in primary care is consistent with the scientific literature on the topic of psychological services in primary care. Common mental health problems are highly prevalent. Societal costs are high. Accurate diagnosis is crucial. There are psychological treatments proven to work, and that are cost effective. We can build on existing multidisciplinary teams and structures in place and also innovate by finding creative mechanisms linking the public and private sectors such as in the Australian primary care system. Interdisciplinary teams should integrate a judicious mix of pertinent skills with the right balance of varying levels of competencies to efficiently address varying levels of problem complexities and co-morbidities. At the moment, there is a gap to be filled in multidisciplinary primary care teams and psychologists are already extensively trained and available to fill this gap. PMID- 27203535 TI - [Publicly funded programs of psychotherapy in Australia and England]. AB - Quebec's HealthCommissioner on the performance of the health system clearly highlighted gaps in the collaboration between primary care physicians and mental health specialists, decreased accessibility and inequity in access to effective mental health services such as psychotherapy.Objectives The aim of this article was to describe the implementation of two publicly funded programs of psychotherapy in Australia and England with similar gatekeeper systems to the one in Quebec.Findings Following the Access to Allied Psychological Services (ATAPS) program introduced in Australia in 2003, one of the most important initiatives from the Council of Australian Governments' National Action Plan on Mental Health 2006-2011 was the Better Access Initiative which commenced in 2006. The plan included AUD1.2 billion in funding for integrating and improving the mental health care system. The purpose of Better Access was to improve the treatment and management of mental illnesses and increasing community access to mental health professionals and providing more affordable mental health care. GPs were encouraged to work more closely with mental health professionals. Under this program, these professionals are able to provide mental health services on a fee for-service basis subsidized through Medicare. Access to psychological therapies is provided through private providers, rather than through fund holding arrangements. As of 2009 in Australia, 2 million people (1 in 11) had received over 11.2 million subsidized mental health services. A recent study showed clinical improvements in patients with depression associated with Better Access, concluding that the program is meeting previously unmet mental health needs.In the case of England, the IAPT - Improving Access to psychological Therapies program enabled primary care trusts (PCTs) to implement evidence-based psychological therapies as recommended by National Institute for Health and Clinical Excellence for people suffering from depression and anxiety. In October 2007, the Secretary of State for Health announced additional funds totalling L173 million between 2008 and 2011 that would be used to deliver a major training program that would build a skilled workforce of qualified psychological therapists in 4 therapy areas for adults and children: cognitive behaviour therapy; psychodynamic psychoanalytic therapy; systemic and family therapy; humanistic therapy. The main goals of the program were to have: (i) 3,600 newly trained therapists with an appropriate skill mix and supervision arrangements; (ii) 900,000 more people treated; (iii) 50% of people who leave treatment are recovered; (iv) 25,000 fewer people on sick pay and benefits.Conclusion To date, the results in both countries have shown clinical improvements in symptoms associated with depression and anxiety for people entering the programs and at a population level, decreasing the unmet mental health needs of the population by allowing self-referrals to the program, and therefore rendering access to services to populations otherwise not reached. PMID- 27203536 TI - [Costs and benefits of a funding program for psychotherapies for French people suffering from depressive or anxious disorders]. AB - Objectives Depressive or anxious disorders are a major source of social and economic burden. Many international good practice guidelines recommend structured psychotherapy for treating depressive or anxious disorders. The positive impact of psychotherapy on health, quality of life, productivity, and on the direct and indirect costs has been widely demonstrated. Nevertheless, the psychotherapies provided in private practice with a non-medical psychotherapist are not reimbursed to patients by French health cover systems.This article aims (1) to assess the cost and benefit of providing a funding program for psychotherapies for the community for French adults suffering from severe or recurrent depressive or anxious disorders, and (2) to estimate the number of psychotherapists that this program would be needed.Methods Data are based on the Enquete Indicateurs de sante mentale dans quatre regions francaises: a cross-sectional survey of a representative sample of 20,777 adults in the general population conducted in 2005. The questionnaires were administered by a telephone interview with the Composite International Diagnostic Interview - short form. A financial evaluation of covering the cost of psychotherapies was performed using the methodology of the British program Improving Access for Psychological Therapies adapted to the French context. The annual cost generated by depressive disorders was estimated at EUR4,702, cost generated by anxiety disorders at EUR1,500. The remission rate attributable to psychotherapies was assessed to be 30% +/-10%. The number of sessions to be covered was defined according to clinical guidelines of the National Institute for Health and Clinical Excellence. The cost of a session was estimated at EUR41, the reimbursement rate by the compulsory health insurance system at 60%.Results The yearly cost for the cover of psychotherapeutic care - for 12.1 sessions on average was M EUR 514 (M EUR 308 for the compulsory systems) to treat 1,033M individuals in France, or 2.3% of the population. In terms of the cost-benefit ratio, EUR1 invested in psychotherapeutic treatment could, save from EUR1.14 (0.76-1.52) to EUR1.95 (1.30-2.60) for anxious or depressive disorders respectively.France has the 14,300 professionals qualified to provide the psychotherapies required to treat this population.Conclusion A funding program for psychotherapies proves to be a cost-efficient investment for the community from the short term, for both direct (health costs) and indirect (productivity, quality of life) costs, that is further that the positive impact and costs of psychotherapy on somatic disorders were not taken into account.With a view to providing appropriate care for patients, inter-professional collaboration among GPs and mental health professionals, and between clinical psychiatrists and psychologists, appears essential. These recommendations should be defined in national good practice guidelines. PMID- 27203537 TI - [Effectiveness of psychotherapy compared to pharmacotherapy for the treatment of anxiety and depressive disorders in adults: A literature review]. AB - Introduction In Quebec, mental disorders affect one in five people in their lifetime. Anxiety and depressive disorders are the main common or moderate mental health disorders. They affect both the individuals with the disorder and the people around them and have substantial economic impact. Psychotropic drugs are the treatment option most often proposed to patients presenting with moderate mental health disorders. Psychotherapy is nevertheless a treatment that should be given consideration.Physical and financial access to psychotherapy remains limited because only one third of professionals qualified to offer it practise in the public sector, and the coverage and reimbursement policy for this service is very restricted. In order to improve such coverage, the Ministere de la Sante et des Services sociaux (MSSS) mandated the Institut national d'excellence en sante et en services sociaux (INESSS) to assess the evidence on the effectiveness of psychotherapy compared with those of pharmacotherapy for the treatment of adults with anxiety and depressive disorders.Methods An update of a review of recent and good quality literature was conducted through a review of systematic reviews dealing with psychotherapy compared to pharmacotherapy in the treatment of anxiety and depression in adults. The period covered included 2009 to 2013. The literature search strategy, modelled on that of the reference review, was applied to Medline, Cochrane Library, CINAHL, Web of Science and health technology assessment agencies. Exploration of the grey literature focused on information available on the websites of various health assessment organizations.Results The level of scientific evidence overall was judged to be of moderate to high quality. In general, the data showed no significant difference between psychotherapy and pharmacotherapy in terms of symptoms reduction in patients with moderate anxiety or depressive disorders, indicating comparable effectiveness of these two modes of treatment. However, the benefits of psychotherapy lasted longer after the end of treatment than those of medication. Psychotherapy therefore offers better protection against relapse. Furthermore, the combination of psychotherapy and pharmacotherapy is more effective than psychotherapy alone in severe or chronic cases.Conclusion Psychotherapy appears to be as effective as pharmacotherapy in the treatment of adult patients with moderate anxiety and/or depressive disorders. Moreover, the beneficial effects of psychotherapy last longer after the end of treatment with a lower likelihood of relapse. PMID- 27203538 TI - [Access to government-funded psychotherapy: Comparing the point of view of psychologists and psychotherapists]. AB - Objectives Within the Quebec context, as well as the larger Canadian and International context, increasing access to mental health care treatment has become a major health care priority (see Peachey, Hicks, & Adams, 2013). Initiatives to increase access through government-funded psychotherapy have been successfully implemented in Australia and the United Kingdom. The current study sought to document how licensed psychologists and psychotherapists in Quebec differ in their attitudes about the components of these government-funded psychotherapy programs and increasing access to psychotherapy treatment.Methods The target population for the study included both psychologists and psychotherapists whom were licensed to practice psychotherapy with the Ordre of Psychologists of Quebec. Participants (N = 1 275) were recruited by email to participate in an online questionnaire focusing on components such as the services that should be offered in a new government-funded psychotherapy model (eg., individual therapy, family therapy; including employment and debt counselling), the choice and autonomy clinicians have in their treatment interventions, the role of the referring General Practitioner (GP), the fees per psychotherapy hour, the hiring structure (e.g., in the public sector versus reimbursing private psychotherapy services), among others.Results The results indicated that psychotherapists were more in favour of including family and couple therapy, and employment/vocational counselling than psychologists. Psychologists were more in favour of using evidence-based practices as well as tracking treatment outcomes using validated measures, and publishing treatment satisfaction ratings to the public. Psychotherapists were more in favour of being paid on a session-to-session basis as opposed to be being hired on a salaried basis to offer government-funded psychotherapy.Conclusions Given that psychologists and psychotherapists differ in their training background and have historically played different roles in the health care system, it is important to understand how they differ in their perspectives on accessibility to psychotherapy. The implications for implementing government-funded psychotherapy initiatives in Quebec given the different professional perspectives of the two groups are discussed. PMID- 27203539 TI - [Initial training in psychotherapy for psychiatrists in France, a national qualitative study]. AB - Objectives To explore the level of satisfaction among residents regarding their training in psychotherapies, the interest they have in these therapies, and their wishes in the area of training.Methods A survey including both a quantitative and qualitative methodology was undertaken among 869 residents out of 1,334 enrolled in the psychiatric residency program. In the 2009-2010 academic year. The survey included five themes of study: theoretical academic training, psychoanalysis, training in institutes outside the university, supervision, wishes in the area of training. This article presents results from the qualitative sociological survey using a semi-guided interview with 27 residents. Their conceptions and practice in the field of psychotherapy, and its place in psychiatric practice were questioned in-depth.Results The vast majority of residents were interested in psychotherapy, but simultaneously dissatisfied with the training they had received. Almost half opted for various sorts of extra-curricular training, costly in time and money. The psychotherapeutic orientations among these residents were varied, and a plurality of methods and theoretical approaches was advocated both for reasons of having a wider viewpoint and good practice in psychiatry, and because the residents considered this plurality to be an essential component in their training. They saw psychotherapy as a medical practice, and considered that it is the responsibility of the psychiatric discipline to provide training in psychotherapies.Conclusion The absence of any real training in psychotherapies for residents in psychiatry is damaging for care quality in psychiatry. The recent creation of a protected title of psychotherapist for psychiatrists without the need of additional training suggests an urgent need to develop a training course. A proposal by the authors should be discussed in light of reflections and proposals already underway in other countries. PMID- 27203540 TI - [Computerized therapy: An option to facilitate access to therapy among young adults?]. AB - Introduction Of all age groups, young Canadian adults have the highest prevalence rates of anxiety and depression. Yet, they are also the least likely to access traditional face-to-face mental health services. Facilitating access to evidence based therapy among young adults is thus particularly important, namely in rural parts of Canada as well as among its linguistic minorities. Computerized therapy could be a cost-effective alternative. However, little is known about how young adults perceive it.Objectives This study aimed to assess the influence of self stigma, need for autonomy and attitudes toward computerized therapy on the intent of Francophone young adults to use computerized therapy. The impact of visiting the Website of a virtual psychology clinic on their intent to use computerized therapy was also assessed.Method Forty-four young adults attending a French University in New Brunswick completed online self-report measures before and after visiting the Website of the MindSpot Clinic, a virtual psychology clinic offering evidence-based computerized therapy programs for anxiety and depression.Results Higher levels of self-stigma were moderately correlated with higher levels of need for autonomy, which in turn were moderately associated with more positive attitudes toward computerized therapy. Only more positive attitudes toward computerized therapy were moderately and directly correlated with a higher intent of using this type of therapy. T-tests revealed that visiting the MindSpot Clinic's Website produced a significant and large increase in the intent to use computerized therapy.Conclusions Computerized therapy may facilitate access to evidence-based treatments of anxiety and depression among Francophone young adults from New Brunswick, and perhaps from other parts of Canada as well. Websites similar to the one of the MindSpot Clinic may be an efficient strategy to provide young Canadian adults with helpful information on computerized therapy, as this therapy format is not established yet in Canada. A research program conducted by the first author aims to make it accessible in New Brunswick in both official languages. PMID- 27203541 TI - [Not Available]. PMID- 27203543 TI - Feasibility of Single Scan for Simultaneous Evaluation of Regional Krypton and Iodine Concentrations with Dual-Energy CT: An Experimental Study. AB - Purpose To evaluate the feasibility of a simultaneous single scan of regional krypton and iodine concentrations by using dual-energy computed tomography (CT). Materials and Methods The study was approved by the institutional animal experimental committee. An airway obstruction model was first made in 10 beagle dogs, and a pulmonary arterial occlusion was induced in each animal after 1 week. For each model, three sessions of dual-energy CT (80% krypton ventilation [krypton CT], 80% krypton ventilation with iodine enhancement [mixed-contrast agent CT], and iodine enhancement [iodine CT]) were performed. Krypton maps were made from krypton and mixed-contrast agent CT, and iodine maps were made from iodine and mixed-contrast agent CT. Observers measured overlay Hounsfield units of the diseased and contralateral segments on each map. Values were compared by using the Wilcoxon signed-rank test. Results In krypton maps of airway obstruction, overlay Hounsfield units of diseased segments were significantly decreased compared with those of contralateral segments in both krypton and mixed contrast agent CT (P = .005 for both). However, the values of mixed-contrast agent CT were significantly higher than those of krypton CT for both segments (P = .005 and .007, respectively). In iodine maps of pulmonary arterial occlusion, values were significantly lower in diseased segments than in contralateral segments for both iodine and mixed-contrast agent CT (P = .005 for both), without significant difference between iodine and mixed-contrast agent CT for both segments (P = .126 and .307, respectively). Conclusion Although some limitations may exist, it might be feasible to analyze regional krypton and iodine concentrations simultaneously by using dual-energy CT. (c) RSNA, 2016. PMID- 27203542 TI - High Incidence of Veno-Occlusive Disease With Myeloablative Chemotherapy Following Craniospinal Irradiation in Children With Newly Diagnosed High-Risk CNS Embryonal Tumors: A Report From the Children's Oncology Group (CCG-99702). AB - BACKGROUND: The outcomes with high-risk central nervous system (CNS) embryonal tumors remain relatively poor despite aggressive treatment. The purposes of this study using postirradiation myeloablative chemotherapy with autologous hematopoietic stem cell rescue (ASCR) were to document feasibility and describe toxicities of the regimen, establish the appropriate dose of thiotepa, and estimate the overall survival (OS) and event-free survival (EFS). PROCEDURE: The Children's Cancer Group conducted this pilot study in children and adolescents with CNS embryonal tumors. The treatment consisted of induction chemotherapy to mobilize hematopoietic stem cells, chemoradiotherapy, and myeloablative consolidation chemotherapy with ASCR. RESULTS: The study accrued 25 subjects in 40 months and was closed early due to toxicity, namely, veno-occlusive disease (VOD) of the liver, more recently termed sinusoidal obstructive syndrome (SOS). Of 24 eligible subjects, three of 11 (27%) receiving thiotepa Dose Level 1 (150 mg/m(2) /day * 3 days) and three of 12 (25%) receiving de-escalated Dose Level 0 (100 mg/m(2) /day * 3 days) experienced VOD/SOS. One additional subject experienced toxic death attributed to septic shock; postmortem examination revealed clinically undiagnosed VOD/SOS. The 2-year EFS and OS were 54 +/- 10% and 71 +/- 9%, respectively. The 5-year EFS and OS were 46 +/- 11% and 50 +/- 11%. CONCLUSIONS: The treatment regimen was deemed to have an unacceptable rate of VOD/SOS. There was complete recovery in all six cases. The overall therapeutic strategy using a regimen less likely to cause VOD/SOS may merit further evaluation for the highest risk patients. PMID- 27203544 TI - Catalysis under Cover: Enhanced Reactivity at the Interface between (Doped) Graphene and Anatase TiO2. AB - The "catalysis under cover" involves chemical processes which take place in the confined zone between a 2D material, such as graphene, h-BN, or MoS2, and the surface of an underlying support, such as a metal or a semiconducting oxide. The hybrid interface between graphene and anatase TiO2 is extremely important for photocatalytic and catalytic applications because of the excellent and complementary properties of the two materials. We investigate and discuss the reactivity of O2 and H2O on top and at the interface of this hybrid system by means of a wide set of dispersion-corrected hybrid density functional calculations. Both pure and boron- or nitrogen-doped graphene are interfaced with the most stable (101) anatase surface of TiO2 in order to improve the chemical activity of the C-layer. Especially in the case of boron, an enhanced reactivity toward O2 dissociation is observed as a result of both the contribution of the dopant and of the confinement effect in the bidimensional area between the two surfaces. Extremely stable dissociation products are observed where the boron atom bridges the two systems by forming very stable B-O covalent bonds. Interestingly, the B defect in graphene could also act as the transfer channel of oxygen atoms from the top side across the C atomic layer into the G/TiO2 interface. On the contrary, the same conditions are not found to favor water dissociation, proving that the "catalysis under cover" is not a general effect, but rather highly depends on the interfacing material properties, on the presence of defects and impurities and on the specific reaction involved. PMID- 27203545 TI - Fucoidan inhibits lymphangiogenesis by downregulating the expression of VEGFR3 and PROX1 in human lymphatic endothelial cells. AB - Lymphangiogenesis is one of the promoters of tumor lymphatic metastasis. Fucoidan which is a fucose-enriched sulfated polysaccharide has effect on various pharmacological activities including anti-metastasis activity. However, the inhibitory effect of fucoidan on lymphangiogenesis remains unclear. Here, fucoidan extracted from U. pinnatifida sporophylls suppressed HLECs proliferation, migration and tube-like structure formation, and had inhibitory effect of tumor-induced lymphangiogenesis in vitro. Additionally, we found that fucoidan had a dose-dependent depressive effect on the expressions of PROX1, vascular endothelial growth factor receptor 3 (VEGFR3), NF-kappaB, phospho-PI3K and phospho-Akt in HLECs. Moreover, anti-lymphangiogenesis effect of fucoidan was assessed by using mouse tumor model. In summary, fucoidan inhibit tumor lymphangiogenesis and lymphatic metastasis by suppressing the NF-kappaB/PI3K/Akt signaling pathway through reduced levels of PROX1 and VEGFR3. PMID- 27203546 TI - Phage display library selection of a hypoxia-binding scFv antibody for liver cancer metabolic marker discovery. AB - : Hypoxia, which is frequently observed in liver cancer and metastasis, influences tumor progression and resistance to therapy. Although hypoxia associated biomarkers are of use in other cancers, none is recognized as a surrogate for hypoxia in liver cancer. In this study, we generated seven unique human single-chain Fv (scFv) antibodies (Abs) specific to hypoxic liver cancer cells, using normoxia-depleted vs hypoxia-selected phage library panning technology. By developing the scFv immunoprecipitation-based mass spectrometry method, the antigen that bound with one of the Abs (H103) was identified as the M2 splice isoform of pyruvate kinase (PKM2), an enzyme that is a key regulator of aerobic glycolysis in cancer cells. Increased expression of PKM2 was induced by hypoxia in liver cancer cell lines. Immunohistochemical (IHC) staining showed that PKM2 was highly expressed in moderately and well differentiated hepatocellular carcinoma (HCC) tissues with a hypovascular staining pattern. High expression of PKM2 was also localized in the perinecrotic area of intrahepatic cholangiocarcinoma (ICC) tissues. The percentage of the HCC or ICC tumor expressing PKM2 was significantly higher with more tumor necrosis, low microvessel density, and advanced stage. Moreover, the H103 scFv Ab was efficiently internalized into hypoxic liver cancer cells and could have potential for targeted drug delivery. CONCLUSION: our study, for the first time, developed hypoxia-specific scFv Ab H103 to liver cancer cells, and revealed that PKM2 is a promising biomarker for hypoxia in HCC and ICC tissues. These allow further exploration of this valuable Ab and PKM2 antigen for hypoxia targeting in liver cancer. PMID- 27203547 TI - Functional role and tobacco smoking effects on methylation of CYP1A1 gene in prostate cancer. AB - Cytochrome P450 (CYP) 1A1 is a phase I enzyme that can activate various compounds into reactive forms and thus, may contribute to carcinogenesis. In this study, we investigated the expression, methylation status, and functional role of CYP1A1 on prostate cancer cells. Increased expression of CYP1A1 was observed in all cancer lines (PC-3, LNCaP, and DU145) compared to BPH-1 (P < 0.05); and was enhanced further by 5-aza-2'-deoxycytidine treatment (P < 0.01). Methylation-specific PCR (MSP) and sequencing of bisulfite-modified DNA of the xenobiotic response element (XRE) enhancer site XRE-1383 indicated promoter methylation as a regulator of CYP1A1 expression. In tissue, microarrays showed higher immunostaining of CYP1A1 in prostate cancer than normal and benign prostatic hyperplasia (BPH; P < 0.001), and methylation analyses in clinical specimens revealed significantly lower methylation levels in cancer compared to BPH at all enhancer sites analyzed (XRE 1383, XRE-983, XRE-895; P < 0.01). Interestingly, smoking affected the XRE-1383 site where the methylation level was much lower in cancer tissues from smokers than non-smokers (P < 0.05). CYP1A1 levels are thus increased in prostate cancer and to determine the functional effect of CYP1A1 on cells, we depleted the gene in LNCaP and DU145 by siRNA. We observe that CYP1A1 knockdown decreased cell proliferation (P < 0.05) and increased apoptosis (P < 0.01) in both cell lines. We analyzed genes affected by CYP1A1 silencing and found that apoptosis-related BCL2 was significantly down-regulated. This study supports an oncogenic role for CYP1A1 in prostate cancer via promoter hypomethylation that is influenced by tobacco smoking, indicating CYP1A1 to be a promising target for prostate cancer treatment. PMID- 27203548 TI - Prognostic impact of history of follicular lymphoma, induction regimen and stem cell transplant in patients with MYC/BCL2 double hit lymphoma. AB - MYC/BCL2 double hit lymphoma (DHL) has been the subject of many studies; however, no study has systemically compared the clinicopathologic features and prognostic factors between patients with de novo disease versus those with a history of follicular lymphoma (FL). In addition, the prognostic importance of several other issues remains controversial in these patients. In this retrospective study, we assess 157 patients with MYC/BCL2 DHL including 108 patients with de novo disease and 49 patients with a history of FL or rarely other types of low-grade B-cell lymphoma. Patients received induction chemotherapy regimens including 61 R-CHOP, 31 R-EPOCH, 29 R-Hyper-CVAD, and 23 other regimens. Thirty-nine patients received a stem cell transplant (SCT) including 31 autologous and 8 allogeneic. Sixty-two patients achieved complete remission (CR) after induction chemotherapy. Median overall survival (OS) was 19 months. Clinicopathologic features were similar between patients with de novo tumors versus those with a history of FL (P > 0.05). Using multivariate analysis, achieving CR, undergoing SCT, stage and the International Prognostic Index were independent prognostic factors for OS. Stem cell transplantion was associated with improved OS in patients who failed to achieve CR, but not in patients who achieved CR after induction chemotherapy. In conclusion, patients with MYC/BCL2 DHL who present with de novo disease and patients with a history of FL have a similarly poor prognosis. Achievement of CR, regardless of the induction chemotherapy regimen used, is the most important independent prognostic factor. Patients who do not achieve CR after induction chemotherapy may benefit from SCT. PMID- 27203550 TI - How is care provided for patients with paediatric trauma and their families in Australia? A mixed-method study. AB - AIM: This study describes clinical staff opinions on the availability and suitability of resources to provide trauma care to children and their families and any perceived strengths, gaps and potential interventions to strengthen care. METHODS: A mixed-method study was conducted in five Australian paediatric trauma centres. The trauma coordinator at each site participated in a structured interview to determine models of care and trauma activity at their site. This informed the development of an electronic survey, which sought staff opinion on child and family access to services and perceived gaps in care. RESULTS: Five trauma coordinators were interviewed, and 214 clinicians (medical, nursing, allied health) from New South Wales, Victoria, South Australia and Queensland completed the survey. Each site had a trauma director and coordinator, and there was variance in resource availability. Almost all survey participants (92.5%) considered their hospital met the physical needs of injured children, 68.2% thought that the psychosocial needs of children were met and 82.1% thought that the needs of families were met. The least accessible services reported were clinical psychology/family counselling, mental health and behaviour management services. No routine follow-up support services post-discharge for the child or their families were identified. CONCLUSION: Staff providing care for injured children report that physical needs are better met than psychosocial needs. There is variability in resource levels across paediatric trauma centres. A coordinated model of care that provides psychosocial care both during hospitalisation and post-discharge could reduce this gap in care for injured children and their families. PMID- 27203551 TI - Milliseconds Make the Difference in the Far-from-Equilibrium Self-Assembly of Supramolecular Chiral Nanostructures. AB - The effect of diffusion-controlled microfluidic conditions in the very initial stages of a far-from-equilibrium self-assembly process on the evolution of aggregate chirality in a multicomponent supramolecular system is shown. PMID- 27203549 TI - S100A7 induction is repressed by YAP via the Hippo pathway in A431 cells. AB - YAP is an oncogenic transcriptional co-activator and is inhibited by the Hippo pathway. Recent studies have revealed that YAP is also a sensor of cell morphology and cell density and can be phosphorylated by cytoskeleton reorganization. Our previous study demonstrated that S100A7 was upregulated in several squamous cell carcinoma (SCC) specimens and was dramatically induced in SCC cells by suspension and dense culture as well as in xenografts. However, little is known about how S100A7 induction occurs in cancer cells. Here, we identify that S100A7 induction is accompanied by YAP phosphorylation in both suspended and dense A431 cells. This correlation reverses after recovery of cell attachment or relief from dense culture. Further examination finds that S100A7 induction is repressed by nuclear YAP, which is further validated by activation or inhibition of the Hippo pathway via loss- and/or gain-of- LATS1 and MST1 function. Strikingly, disruption of the F-actin promotes S100A7 expression via YAP by activation of the Hippo pathway. Furthermore, we demonstrate that repression of S100A7 by YAP required TEAD1 transcriptional factor. Taken together, our findings demonstrate for the first time that S100A7 is repressed by YAP via the Hippo pathway. PMID- 27203552 TI - Identity Processes and Parent-Child and Sibling Relationships in Adolescence: A Five-Wave Multi-Informant Longitudinal Study. AB - The purpose of this study was to examine reciprocal associations between identity processes (commitment, in-depth exploration, and reconsideration of commitment) and dimensions (support, negative interaction, and power) of maternal, paternal, and sibling relationships. A total of 497 Dutch families including 14-years-old adolescents (56.9% males), their fathers, mothers, and siblings, for a total of 1,988 respondents, participated in a five-wave longitudinal study. Cross-lagged analyses indicated that commitment and in-depth exploration predicted improvements in family relationships (unidirectional effects), whereas reconsideration of commitment was predicted by low levels of maternal support and worsened the quality of the paternal relationship (reciprocal effects). These results were not moderated by adolescents' gender and sibling characteristics. Theoretical and practical implications are discussed. PMID- 27203553 TI - Parsimonious kernel extreme learning machine in primal via Cholesky factorization. AB - Recently, extreme learning machine (ELM) has become a popular topic in machine learning community. By replacing the so-called ELM feature mappings with the nonlinear mappings induced by kernel functions, two kernel ELMs, i.e., P-KELM and D-KELM, are obtained from primal and dual perspectives, respectively. Unfortunately, both P-KELM and D-KELM possess the dense solutions in direct proportion to the number of training data. To this end, a constructive algorithm for P-KELM (CCP-KELM) is first proposed by virtue of Cholesky factorization, in which the training data incurring the largest reductions on the objective function are recruited as significant vectors. To reduce its training cost further, PCCP-KELM is then obtained with the application of a probabilistic speedup scheme into CCP-KELM. Corresponding to CCP-KELM, a destructive P-KELM (CDP-KELM) is presented using a partial Cholesky factorization strategy, where the training data incurring the smallest reductions on the objective function after their removals are pruned from the current set of significant vectors. Finally, to verify the efficacy and feasibility of the proposed algorithms in this paper, experiments on both small and large benchmark data sets are investigated. PMID- 27203554 TI - A recurrent neural network for adaptive beamforming and array correction. AB - In this paper, a recurrent neural network (RNN) is proposed for solving adaptive beamforming problem. In order to minimize sidelobe interference, the problem is described as a convex optimization problem based on linear array model. RNN is designed to optimize system's weight values in the feasible region which is derived from arrays' state and plane wave's information. The new algorithm is proven to be stable and converge to optimal solution in the sense of Lyapunov. So as to verify new algorithm's performance, we apply it to beamforming under array mismatch situation. Comparing with other optimization algorithms, simulations suggest that RNN has strong ability to search for exact solutions under the condition of large scale constraints. PMID- 27203555 TI - Continuous subcutaneous glucose monitoring is accurate in term and near-term infants at risk of hypoglycaemia. AB - AIM: Postnatal hypoglycaemia increases the risk of adverse neurological outcomes in newborn infants, and adequate glucose control requires repetitive and painful blood sampling. This study evaluated a continuous glucose monitoring system (CGMS) that aims to improve glucose control and decrease the frequency of blood samples taken from neonates. METHODS: CGMS sensors, which measure glucose values every five minutes and require calibration twice a day, were placed on 20 infants at risk of hypoglycaemia. The infants also underwent blood glucose sampling, and the blood glucose values were compared with CGMS values six times during the first 30 minutes after sampling. RESULTS: We used 97/264 (37%) of the blood glucose values taken for the CGMS calibration. The highest accuracy, a mean of 0.22 (95% confidence interval 0.13-0.30 mmol/L), was found 15-19 minutes after sampling, due to the calibration process. No significant subcutaneous glucose time lag was detectable. CONCLUSION: The CGMS system was an accurate and feasible method for glucose control, provided earlier detection of hypoglycaemia in newborn infants and reduced their exposure to procedural pain. The delay in calibration in infants was a new finding and needs to be taken into account when comparing CGMS readings to blood glucose values. PMID- 27203556 TI - Breakage-fusion-bridge cycles and de novo telomere formation on broken chromosomes in maize callus cultures. AB - Breakpoints involved in chromosome alterations associated with heterochromatin have been detected in maize plants regenerated from callus culture. A cytogenetic analysis of plants regenerated from a maize callus was performed aiming to analyze the stability of a chromosome 7 bearing a deficiency-duplication (Df-Dp), which was interpreted as derived from a chromatid type breakage-fusion-bridge (BFB) cycle. The Df-Dp chromosome 7 was stable in mitotic and meiotic cells of the regenerated plants. Fluorescence in situ hybridization showed signals of telomeric sequences on the broken chromosome arm and provided evidence of de novo telomere formation. The stability of two types of altered chromosome 7 was investigated in C-banded metaphases from samples of the original callus that were collected during a period of 30-42 months after culture initiation. New alterations involving heterochromatic knobs of chromosomes 7 and 9 were observed. The aberrant chromosomes were stable in the subcultures, thus providing evidence of broken chromosome healing. The examination of anaphases showed the presence of bridges, which was consistent with the occurrence of BFB cycles. De novo telomere formation occurred in euchromatic and heterochromatic chromosome termini. The results point to events of chromosomal evolution that might occur in plants. PMID- 27203557 TI - Multilevel Nonvolatile Memristive and Memcapacitive Switching in Stacked Graphene Sheets. AB - We fabricated devices consisting of single and double graphene sheets embedded in organic polymer layers. These devices had binary and ternary nonvolatile resistive switching behaviors, respectively. Capacitance-voltage (C-V) curves and scanning capacitance microscopy (SCM) images were obtained to investigate the switching mechanism. The C-V curves exhibited a large hysteresis, implying that the graphene sheets acted as charging and discharging layers and that resistive switching was caused by charges trapped in the graphene layers. In addition, binary capacitive switching behaviors were observed for the device with a single graphene sheet, and ternary capacitive switching behaviors were observed for the device with the double graphene sheets. These results demonstrated that devices consisting of graphene sheets embedded in the polymer layers can be applied to multilevel nonvolatile memcapacitive devices as well as memristive devices. PMID- 27203558 TI - Electrical, Mechanical, and Capacity Percolation Leads to High-Performance MoS2/Nanotube Composite Lithium Ion Battery Electrodes. AB - Advances in lithium ion batteries would facilitate technological developments in areas from electrical vehicles to mobile communications. While two-dimensional systems like MoS2 are promising electrode materials due to their potentially high capacity, their poor rate capability and low cycle stability are severe handicaps. Here, we study the electrical, mechanical, and lithium storage properties of solution-processed MoS2/carbon nanotube anodes. Nanotube addition gives up to 10(10)-fold and 40-fold increases in electrical conductivity and mechanical toughness, respectively. The increased conductivity results in up to a 100* capacity enhancement to ~1200 mAh/g (~3000 mAh/cm(3)) at 0.1 A/g, while the improved toughness significantly boosts cycle stability. Composites with 20 wt % nanotubes combine high reversible capacity with excellent cycling stability (e.g., ~950 mAh/g after 500 cycles at 2 A/g) and high rate capability (~600 mAh/g at 20 A/g). The conductivity, toughness, and capacity scale with nanotube content according to percolation theory, while the stability increases sharply at the mechanical percolation threshold. We believe that the improvements in conductivity and toughness obtained after addition of nanotubes can be transferred to other electrode materials, such as silicon nanoparticles. PMID- 27203559 TI - A RARE COMPLICATION OF POSTERIOR SUBTENON INJECTION. AB - PURPOSE: To report a case of posterior ciliary artery occlusion after posterior subtenon injection. METHODS: Clinical examination and fundus fluorescein angiography was performed to confirm diagnosis. A 49-year-old female who was on treatment for bilateral chronic sclerokeratouveitis was given posterior subtenon injection for cystoid macular edema. RESULTS: Posterior ciliary artery occlusion occurred after posterior subtenon injection. CONCLUSION: Choroidal vascular occlusion is a rare complication of posterior subtenon injection. PMID- 27203560 TI - SURGICAL TREATMENT OF A MACULAR HOLE IN X-LINKED RETINOSCHISIS. AB - PURPOSE: To report a case of full-thickness macular hole in a patient with X linked retinoschisis and the outcome after surgical repair. METHODS: A 15-year old boy with a history of X-linked retinoschisis presented to his ophthalmologist for routine follow-up and was found to have a Stage-3 macular hole in his left eye. His vision was 20/200. The patient underwent pars plana vitrectomy and internal limiting membrane peeling, and he received long-acting gas. Color fundus photography and spectral domain optical coherence tomography (Cirrus; Carl Zeiss Meditech Inc, Dublin, CA) recorded images at office visits, before and after surgical repair. RESULTS: The initial spectral domain optical coherence tomography of the left eye showed a full-thickness macular hole of 1,370 MUm in diameter as well as schisis cavities in the macula. After pars plana vitrectomy and repeat fluid-gas exchange, the hole was closed at the sixth-week follow-up visit. The patient noted a subjective decrease in the size of a central scotoma. Best-corrected visual acuity returned to the baseline of 20/80. CONCLUSION: A large full-thickness macular hole can develop in X-linked retinoschisis, and pars plana vitrectomy with internal limiting membrane peeling may be helpful for successful surgical closure. PMID- 27203561 TI - LEBER CONGENITAL AMAUROSIS WITH LARGE RETINAL PIGMENT CLUMPS CAUSED BY COMPOUND HETEROZYGOUS MUTATIONS IN KCNJ13. AB - PURPOSE: To describe a patient with mutations in KCNJ13 presenting particular clinical features. METHODS: Standard ophthalmic examination, fundus autofluorescence, spectral domain optical coherence tomography, full-field electroretinography. The 3 exons of KCNJ13 were polymerase chain reaction amplified and Sanger sequenced. PATIENTS: A 31-year-old man with Leber congenital amaurosis. RESULTS: Patient had nystagmus since childhood, best-corrected visual acuity limited to 20/400 OD and 20/200 OS, and had cataracts extracted in both eyes. There were clumpy pigment deposits mostly in macular area, causing an uneven line of retinal pigment epithelium on spectral domain optical coherence tomography. In retinal parts devoid of pigment deposits around the optic disk and in periphery, retinal thickness was increased and hyperreflective formations were present either in the inner nuclear layer or in the outer nuclear layer. The patient was compound heterozygous for new mutations in KCNJ13 which encodes the Kir 7.1 potassium channel, c.314G>T (p.Ser105Ile) in exon 2 and c.655C>T (p.Gln219*) in exon 3. Both mutations were absent from databases. CONCLUSION: KCNJ13 mutations are responsible for early-onset retinal dystrophy, featuring remarkable clumpy pigment deposits at the level of the retinal pigment epithelium, suggesting dysfunction and disorganization of this tissue. Parts of the retina remain relatively preserved anatomically but are increased in thickness. This distinct fundus appearance should help in identifying the "KCNJ13 retinal dystrophy" to orient the molecular diagnosis. PMID- 27203562 TI - ACUTE SEROUS RETINAL DETACHMENT IN IDIOPATHIC PULMONARY ARTERIAL HYPERTENSION. AB - PURPOSE: To report the case of a 44-year-old woman with acute transient visual loss likely because of idiopathic pulmonary arterial hypertension. METHODS: Case report imaged with fundus photographs, spectral-domain optical coherence tomography, fundus autofluorescence, and fluorescein and indocyanine green angiographies. RESULTS: The patient complained of unilateral vision loss with metamorphopsia. Fundus examination of the right eye showed serous macular detachment and retinal folds. Fluorescein angiography and indocyanine green angiography showed delayed choroidal filling with multiple choroidal perfusion defects and dye leakage from areas of multiple pigment epithelial detachments. Spectral-domain optical coherence tomography showed a thick choroid. Medical history included idiopathic pulmonary arterial hypertension treated with tadalafil. Ocular signs regressed spontaneously within 1 week. CONCLUSION: Transient severe choroidal filling defects with subretinal exudation may be observed in idiopathic pulmonary arterial hypertension. The present case raised the questions of the triggering factor of the acute decompensation of the blood retinal barrier and the cause of its spontaneous regression. PMID- 27203565 TI - Apoptosis and morphological alterations after UVA irradiation in red blood cells of p53 deficient Japanese medaka (Oryzias latipes). AB - Morphological alterations in red blood cells were described as hematological bioindicators of UVA exposure to investigate the sensitivity to UVA in wild type Japanese medaka (Oryzias latipes) and a p53 deficient mutant. The fewer abnormal red blood cells were observed in the p53 mutant fish under the control conditions. After exposure to different doses of UVA radiation (15min, 30min and 60min/day for 3days), cellular and nuclear alterations in red blood cells were analyzed in the UVA exposed fish compared with non-exposed controls and those alterations included acanthocytes, cell membrane lysis, swollen cells, teardrop like cell, hemolyzed cells and sickle cells. Those alterations were increased after the UVA exposure both in wild type and the p53 deficient fish. Moreover, apoptosis analyzed by acridine orange assay showed increased number of apoptosis in red blood cells at the higher UVA exposure dose. No micronuclei but nuclear abnormalities as eccentric nucleus, nuclear budding, deformed nucleus, and bilobed nucleus were observed in each group. These results suggested that UVA exposure induced both p53 dependent and independent apoptosis and morphological alterations in red blood cells but less sensitive to UVA than Wild type in medaka fish. PMID- 27203564 TI - Management of Prematurity-Associated Wheeze and Its Association with Atopy. AB - INTRODUCTION: Although preterm birth is associated with respiratory morbidity in childhood, the role of family history of atopy and whether appropriate treatment has been instituted is unclear. Thus we assessed (i) the prevalence of respiratory symptoms, particularly wheezing, in childhood; (ii) evaluated the role of family history of atopy and mode of delivery, and (iii) documented the drug usage, all in preterm-born children compared to term-born control children. METHODS: We conducted a cross-sectional population-based questionnaire study of 1 10 year-old preterm-born children (n = 13,361) and matched term-born controls (13,361). Data (n = 7,149) was analysed by gestational groups (24-32 weeks, 33-34 weeks, 35-36 weeks and 37-43 weeks) and by age, <5 years old or >= 5 years. MAIN RESULTS: Preterm born children aged <5 years (n = 2,111, term n = 1,402) had higher rates of wheeze-ever [odds ratio: 2.7 (95% confidence intervals 2.2, 3.3); 1.8 (1.5, 2.2); 1.5 (1.3, 1.8) respectively for the 24-32 weeks, 33-34 weeks, 35 36 weeks groups compared to term]. Similarly for the >=5 year age group (n = 2,083, term n = 1,456) wheezing increased with increasing prematurity [odds ratios 3.3 (2.7, 4.1), 1.8 (1.5, 2.3) and 1.6 (1.3, 1.9) for the three preterm groups compared to term]. At both age groups, inhaler usage was greater in the lowest preterm group but prematurity-associated wheeze was independent of a family history of atopy. CONCLUSIONS: Increasing prematurity was associated with increased respiratory symptoms, which were independent of a family history of atopy. Use of bronchodilators was also increased in the preterm groups but its efficacy needs careful evaluation. PMID- 27203563 TI - A Detailed Data-Driven Network Model of Prefrontal Cortex Reproduces Key Features of In Vivo Activity. AB - The prefrontal cortex is centrally involved in a wide range of cognitive functions and their impairment in psychiatric disorders. Yet, the computational principles that govern the dynamics of prefrontal neural networks, and link their physiological, biochemical and anatomical properties to cognitive functions, are not well understood. Computational models can help to bridge the gap between these different levels of description, provided they are sufficiently constrained by experimental data and capable of predicting key properties of the intact cortex. Here, we present a detailed network model of the prefrontal cortex, based on a simple computationally efficient single neuron model (simpAdEx), with all parameters derived from in vitro electrophysiological and anatomical data. Without additional tuning, this model could be shown to quantitatively reproduce a wide range of measures from in vivo electrophysiological recordings, to a degree where simulated and experimentally observed activities were statistically indistinguishable. These measures include spike train statistics, membrane potential fluctuations, local field potentials, and the transmission of transient stimulus information across layers. We further demonstrate that model predictions are robust against moderate changes in key parameters, and that synaptic heterogeneity is a crucial ingredient to the quantitative reproduction of in vivo like electrophysiological behavior. Thus, we have produced a physiologically highly valid, in a quantitative sense, yet computationally efficient PFC network model, which helped to identify key properties underlying spike time dynamics as observed in vivo, and can be harvested for in-depth investigation of the links between physiology and cognition. PMID- 27203566 TI - Effect of melatonin on monochromatic light-induced T-lymphocyte proliferation in the thymus of chickens. AB - A total of 360 post-hatching day 0 (P0) Arbor Acre male broilers, including intact, sham operation and pinealectomy groups, were exposed to white light (WL), red light (RL), green light (GL) and blue light (BL) from a light-emitting diode (LED) system until for P14. We studied the effects of melatonin and its receptors on monochromatic light-induced T-lymphocyte proliferation in the thymus of broilers. The density of proliferating cell nuclear antigen (PCNA) cells and the proliferation of T-lymphocytes in response to Concanavalin A (ConA) in GL significantly increased both in vivo and in vitro (from 9.57% to 32.03% and from 34.30% to 50.53%, respectively) compared with other lights (p<0.005) and was strongly correlated with melatonin levels in plasma (p<0.005). Pinealectomy reduced the levels of circulatory melatonin and the proliferation of T lymphocytes and eliminated the differences between GL and other lights (p<0.005). However, exogenous melatonin (10(-9)M) significantly increased the proliferative activity of T-lymphocyte by 9.64% (p=0.002). In addition, GL significantly increased mRNA expression levels of Mel1a, Mel1b and Mel1c receptors from 21.09% to 32.57%, and protein expression levels from 24.43% to 42.92% compared with RL (p<0.05). However, these effects were blocked after pinealectomy. Furthermore, 4P PDOT (a selective Mel1b antagonist) and prazosin (a selective Mel1c antagonist) attenuated GL-induced T-lymphocyte proliferation in response to ConA (p=0.000). Luzindole (a nonselective Mel1a/Mel1b antagonist), however, did not induce these effects (p=0.334). These results suggest that melatonin may mediate GL-induced T lymphocyte proliferation via the Mel1b and Mel1c receptors but not via the Mel1a receptor. PMID- 27203567 TI - Isatis tinctoria mediated synthesis of amphotericin B-bound silver nanoparticles with enhanced photoinduced antileishmanial activity: A novel green approach. AB - After malaria, Leishmaniasis is the most prevalent infectious disease in terms of fatality and geographical distribution. The availability of a limited number of antileishmanial agents, emerging resistance to the available drugs, and the high cost of treatment complicate the treatment of leishmaniasis. To overcome these issues, critical research for new therapeutic agents with enhanced antileishmanial potential and low treatment cost is needed. In this contribution, we developed a green protocol to prepare biogenic silver nanoparticles (AgNPs) and amphotericin B-bound biogenic silver nanoparticles (AmB-AgNPs). Phytochemicals from the aqueous extract of Isatis tinctoria were used as reducing and capping agents to prepare silver nanoparticles. Amphotericin B was successfully adsorbed on the surface of biogenic silver nanoparticles. The prepared nanoparticles were characterized by various analytical techniques. UV Visible spectroscopy was employed to detect the characteristic localized surface plasmon resonance peaks (LSPR) for the prepared nanoparticles. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) studies revealed the formation of spherical silver nanoparticles with an average particle size of 10 20nm. The cubic crystalline structure of the prepared nanoparticles was confirmed by X-ray diffraction (XRD) study. FTIR spectroscopic analysis revealed that plant polyphenolic compounds are mainly involved in metal reduction and capping. Under visible light irradiation, biogenic silver nanoparticles exhibited significant activity against Leishmania tropica with an IC50 value of 4.2MUg/mL. The leishmanicidal activity of these nanoparticles was considerably enhanced by conjugation with amphotericin B (IC50=2.43MUg/mL). In conclusion, the findings of this study reveal that adsorption of amphotericin B, an antileishmanial drug, to biogenic silver nanoparticles, could be a safe, more effective and economic alternative to the available antileishmanial strategies. PMID- 27203568 TI - Effect of reduced graphene oxide-hybridized ZnO thin films on the photoinactivation of Staphylococcus aureus and Salmonella enterica serovar Typhi. AB - The immobilization of photocatalyst nanoparticles on a solid substrate is an important aspect for improved post-treatment separation and photocatalyst reactor design. In this study, we report the simple preparation of reduced graphene oxide (rGO)-hybridized zinc oxide (ZnO) thin films using a one-step electrochemical deposition, and investigated the effect of rGO-hybridization on the photoinactivation efficiency of ZnO thin films towards Staphylococcus aureus (S. aureus) and Salmonella enterica serovar Typhi (S. Typhi) as target bacterial pathogens. Field-emission scanning electron microscopy (FESEM) revealed the formation of geometric, hexagonal flakes of ZnO on the ITO glass substrate, as well as the incorporation of rGO with ZnO in the rGO/ZnO thin film. Raman spectroscopy indicated the successful incorporation of rGO with ZnO during the electrodeposition process. Photoluminescence (PL) spectroscopy indicates that rGO hybridization with ZnO increases the amount of oxygen vacancies, evidenced by the shift of visible PL peak at 650 to 500nm. The photoinactivation experiments showed that the thin films were able to reduce the bacterial cell density of Staph. aureus and S. Typhi from an initial concentration of approximately 10(8) to 10(3)CFU/mL within 15min. The rGO/ZnO thin film increased the photoinactivation rate for S. aureus (log[N/No]) from -5.1 (ZnO) to -5.9. In contrast, the application of rGO/ZnO thin film towards the photoinactivation of S. Typhi did not improve its photoinactivation rate, compared to the ZnO thin film. We may summarise that (1) rGO/ZnO was effective to accelerate the photoinactivation of S. aureus but showed no difference to improve the photoinactivation of S. Typhi, in comparison to the performance of ZnO thin films, and (2) the photoinactivation in the presence of ZnO and rGO/ZnO was by ROS damage to the extracellular wall. PMID- 27203569 TI - The influence of maternal self-objectification, materialism and parenting style on potentially sexualized 'grown up' behaviours and appearance concerns in 5 8year old girls. AB - There is widespread concern about young girls displaying 'grown up' or sexualized behaviours, as well as experiencing body image and appearance concerns that were previously thought to only impact much older girls. The present study examined the influence of three maternal attributes, self-objectification, materialism and parenting style, on sexualized behaviours and appearance concerns in young girls. A sample of 252 Australian mothers of 5-8year old girls reported on the behaviours and appearance concerns observed in their daughters and also completed measures of their own self-objectification, materialism and parenting style. It was found that a significant proportion of young girls were engaging with 'teen' culture, using beauty products and expressing some degree of appearance concern. Maternal self-objectification was related to daughters' engagement in teen culture, use of beauty products and appearance concern. Maternal materialism was related to girls' engagement in teen culture and appearance concern, while an authoritative parenting style was negatively related to girls' use of beauty products. The findings suggest that maternal self-objectification and materialism play a role in the body image and appearance concerns of young girls, and in so doing, identify these maternal attributes as novel potential targets for intervention. PMID- 27203570 TI - Resolution of Elevated Urine Glycosaminoglycans and Clinical Features of Mucopolysaccharidosis After Successful Treatment of Neuroblastoma. AB - We report a patient with stage 3 ganglioneuroblastoma who initially presented with clinical and laboratory features consistent with mucopolysaccharidosis including coarse facial features, developmental delay, and an elevated quantitative urine glycosaminoglycan (GAG) level. All mucopolysaccharidosis features resolved following successful treatment of neuroblastoma. High GAG levels have been documented in the pediatric oncology literature, yet not as a potential marker of malignancy or other target for clinical utility. This patient prompts further investigation into the relationship between neuroblastoma and elevated GAG levels. PMID- 27203572 TI - Correction: Caspase-1-Like Regulation of the proPO-System and Role of ppA and Caspase-1-Like Cleaved Peptides from proPO in Innate Immunity. AB - [This corrects the article DOI: 10.1371/journal.ppat.1004059.]. PMID- 27203571 TI - Activation of Nesfatin-1-Containing Neurones in the Hypothalamus and Brainstem by Peripheral Administration of Anorectic Hormones and Suppression of Feeding via Central Nesfatin-1 in Rats. AB - Peripheral anorectic hormones, such as glucagon-like peptide (GLP)-1, cholecystokinin (CCK)-8 and leptin, suppress food intake. The newly-identified anorectic neuropeptide, nesfatin-1, is synthesised in both peripheral tissues and the central nervous system, particularly by various nuclei in the hypothalamus and brainstem. In the present study, we examined the effects of i.p. administration of GLP-1 and CCK-8 and co-administrations of GLP-1 and leptin at subthreshold doses as confirmed by measurement of food intake, on nesfatin-1 immunoreactive (-IR) neurones in the hypothalamus and brainstem of rats by Fos immunohistochemistry. Intraperitoneal administration of GLP-1 (100 MUg/kg) caused significant increases in the number of nesfatin-1-IR neurones expressing Fos immunoreactivity in the supraoptic nucleus (SON), the area postrema (AP) and the nucleus tractus solitarii (NTS) but not in the paraventricular nucleus (PVN), the arcuate nucleus (ARC) or the lateral hypothalamic area (LHA). On the other hand, i.p. administration of CCK-8 (50 MUg/kg) resulted in marked increases in the number of nesfatin-1-IR neurones expressing Fos-immunoreactivity in the SON, PVN, AP and NTS but not in the ARC or LHA. No differences in the percentage of nesfatin-1-IR neurones expressing Fos-immunoreactivity in the nuclei of the hypothalamus and brainstem were observed between rats treated with saline, GLP-1 (33 MUg/kg) or leptin. However, co-administration of GLP-1 (33 MUg/kg) and leptin resulted in significant increases in the number of nesfatin-1-IR neurones expressing Fos-immunoreactivity in the AP and the NTS. Furthermore, decreased food intake induced by GLP-1, CCK-8 and leptin was attenuated significantly by pretreatment with i.c.v. administration of antisense nesfatin-1. These results indicate that nesfatin-1-expressing neurones in the brainstem may play an important role in sensing peripheral levels of GLP-1 and leptin in addition to CCK-8, and also suppress food intake in rats. PMID- 27203573 TI - Exogenous Cytokinins Increase Grain Yield of Winter Wheat Cultivars by Improving Stay-Green Characteristics under Heat Stress. AB - Stay-green, a key trait of wheat, can not only increase the yield of wheat but also its resistance to heat stress during active photosynthesis. Cytokinins are the most potent general coordinator between the stay-green trait and senescence. The objectives of the present study were to identify and assess the effects of cytokinins on the photosynthetic organ and heat resistance in wheat. Two winter wheat cultivars, Wennong 6 (a stay-green cultivar) and Jimai 20 (a control cultivar), were subjected to heat stress treatment from 1 to 5 days after anthesis (DAA). The two cultivars were sprayed daily with 10 mg L-1 of 6 benzylaminopurine (6-BA) between 1 and 3 DAA under ambient and elevated temperature conditions. We found that the heat stress significantly decreased the number of kernels per spike and the grain yield (P < 0.05). Heat stress also decreased the zeatin riboside (ZR) content, but increased the gibberellin (GA3), indole-3-acetic acid (IAA), and abscisic acid (ABA) contents at 3 to 15 DAA. Application of 6-BA significantly (P < 0.05) increased the grain-filling rate, endosperm cell division rate, endosperm cell number, and 1,000-grain weight under heated condition. 6-BA application increased ZR and IAA contents at 3 to 28 DAA, but decreased GA3 and ABA contents. The contents of ZR, ABA, and IAA in kernels were positively and significantly correlated with the grain-filling rate (P < 0.05), whereas GA3 was counter-productive at 3 to 15 DAA. These results suggest that the decrease in grain yield under heat stress was due to a lower ZR content and a higher GA3 content compared to that at elevated temperature during the early development of the kernels, which resulted in less kernel number and lower grain-filling rate. The results also provide essential information for further utilization of the cytokinin substances in the cultivation of heat-resistant wheat. PMID- 27203575 TI - Instant and Persistent Antidepressant Response of Gardenia Yellow Pigment Is Associated with Acute Protein Synthesis and Delayed Upregulation of BDNF Expression in the Hippocampus. AB - Gardenia yellow pigment (GYP) is a collection of compounds with shared structure of crocin, which confers antidepressant activity. GYP is remarkably enriched in Gardenia jasminoides Ellis, implicated in rapid antidepressant effects that are exerted through enhanced neuroplasticity. This study aims to investigate the rapid antidepressant-like activity of GYP and its underlying mechanism. After the optimal dose was determined, antidepressant responses in tail suspension test or forced swim test were monitored at 30 min, 1 day, 3 days, and 7 days post a single GYP administration. Rapid antidepressant potential was tested using learned helplessness paradigm. The expression of proteins involved in hippocampal neuroplasticity was determined. The effect of blockade of protein synthesis on GYP's antidepressant response was examined. Antidepressant response was detected at 30 min, and lasted for at least 3 days post a single administration of GYP. A single administration of GYP also reversed the deficits in learned helplessness test. Thirty minutes post GYP administration, ERK signaling was activated, and its downstream effector phosphorylated eukaryotic elongation factor 2 was inhibited, contributing to increased protein translation. Expression of synaptic proteins GluR1 and synapsin 1 was upregulated. Blockade of protein synthesis with anisomycin blunted the immediate antidepressant response of GYP. CREB signaling and BDNF expression were upregulated at 24 h, but not at 30 min. In conclusion, GYP-induced immediate antidepressant response was dependent on synthesis of proteins, including synaptic proteins. This was followed by enhanced expression of CREB and BDNF, which likely mediated the persistent antidepressant responses. PMID- 27203574 TI - Various modifications of the amphipathic dynorphin A pharmacophore for rat brain bradykinin receptors. AB - As a unique endogenous opioid ligand, dynorphin A shows paradoxical neuroexcitatory effects at bradykinin receptors, and the effects are known to be amplified by the upregulation of dynorphin A under chronic pain and inflammatory conditions. In our earlier structure-activity relationship studies, the amphipathic dynorphin A fragment, [Des-Arg(7) ]-Dyn A-(4-11), was identified as a pharmacophore for the bradykinin receptors along with key structural features. Here, further modifications of the pharmacophore showed that the position of a Pro residue is also an important feature because of its role in making (or disrupting) a beta-turn or 310 helix structure which is crucial for receptor recognition. PMID- 27203576 TI - A Comparison of Bone Mineral Density in Amateur Male Boxers and Active Non boxers. AB - To examine the site-specific osteogenic effect of upper limb impact-loading activity we compared the forearm and arm bone mineral density (BMD) of male boxers to that of active controls. A cross-sectional study was performed with 30 amateur male boxers (aged 18-44 years) and 32 age-matched, non-boxing, active controls. Participants had their regional and whole body BMD and bone mineral content (BMC) assessed by dual-energy X-ray absorptiometry. Hand grip strength, testosterone, oestradiol, sex hormone-binding globulin, vitamin D, lean and fat mass, and past and current physical activity were also assessed. Forearm and arm BMD were 1.5-2.2% higher in boxers than the control group although this was not statistically significant (p>0.05), with no significant difference for BMC (p>0.05). There were no differences between groups for spine, hip, or whole body BMD or BMC, or for body composition or hormone status. Within the arms, lean mass was associated with BMD and BMC in both boxers and the control group (BMD, r=0.60 0.76, p<0.001; BMC, r=0.67-0.82, p<0.001). There were no significant differences between amateur boxers and the control group for upper limb BMD and BMC. However, muscle mass appears to be particularly important to bone health of the upper limbs. PMID- 27203577 TI - Line-assisted complete closure of a large colorectal mucosal defect after endoscopic submucosal dissection. PMID- 27203578 TI - Endothelial dysfunction in human essential hypertension. AB - Although the endothelium has a number of important functions, the term endothelial dysfunction is commonly used to describe impairment in its vasodilatory capacity. It is increasingly recognized that this is related to hypertension, although whether it predates essential hypertension or is a consequence of it is still unknown. In this review, we explore the mechanisms of endothelial dysfunction in essential hypertension, its prognostic significance and methods of pharmacological reversal. PMID- 27203579 TI - Phenotypes of office systolic blood pressure according to both brachial and aortic measurements: frequencies and associations with carotid hypertrophy in 1861 adults. AB - BACKGROUND/AIM: Aortic SBP (aSBP) associates with arterial damage more consistently than brachial SBP (bSBP). However, it is unknown how often aSBP is normal in the presence of elevated bSBP, and vice versa; if SBP phenotyping on the basis of bSBP and aSBP cut-off values improves cardiovascular risk stratification. We tested the frequency of four office SBP phenotypes: type I (both normal bSBP and aSBP); type II (high bSBP but normal aSBP); type III (normal bSBP but high aSBP), and type IV (both high bSBP and aSBP), the probability of each phenotype to be associated with increased arterial damage, using type Ia (i.e. normal bSBP and low-normal aSBP) as reference. METHODS: In 1861 participants (age: 54 years, 49.1% men), we measured simultaneously bSBP, aSBP, and carotid cross-sectional wall area with ultrasound. RESULTS: Depending on the applied cut-off values, type II and type III phenotypes represented together 5-11% of the population (0.9-3.4 and 1.8-10.3%, respectively) and type IV around 20%. Subgroups with phenotypes, Ib (i.e. normal bSBP and high-normal aSBP), II, III, and IV had gradually significantly higher probability (by 1.37 1.91, 2.3-3.3, 3.3-8.9 times, and 4.18-6.25, respectively) to present elevated carotid artery cross-sectional wall area compared with the reference group, even after adjustment for DBP and other confounders. CONCLUSIONS: Type II (i.e. isolated high bSBP) and type III (i.e. isolated high aSBP) office SBP phenotypes were common and had intermediate level (between types I and IV) of arterial damage. PMID- 27203580 TI - Living my narrative: storying dishonesty and deception in mental health nursing. AB - This article proceeds from MacIntyre's moral philosophical perspective of individual human lives constituting unified narratives, in the context of co evolving framing and guiding master narratives. This perspective accords specific episodes in people's lives the status of significant component parts of their developing, storied and enacted individual histories. From this philosophical base, autoethnographic principles will be employed in providing accounts from my own professional life narrative strand as a mental health nurse educator that speak to the issue of institutionalized dishonesty and deception in mental health nursing education and practice. On the basis of my pre-existing experience of publishing in nursing journals and scholarly identity, my argument will proceed from contesting the idea of an imagined stable foundational professional ethos underpinning mental health nursing practice, against which to judge professional dishonesty and deception. Using illustrative, relatively recent short stories, drawn from my lived-experience base as a mental health nurse educator, I will argue throughout at implicit and explicit levels that dishonesty and deception are always an inevitable part of the lives of mental health nurses and their educators. This is because of a constant gap between the nursing rhetoric and ideology that both groups espouse and how they actually behave on a day-to-day, mundane level, in and out of work and classroom practice. This gap shows up the public front of what mental health nursing is supposed to be about as dishonest and deceitful window dressing. I will assert that the many first-person, lived experience accounts in mental health nursing teaching and publication are important educational resources in reducing this gap at professional practice, academic, and informal levels. Such storied accounts may also be useful in moving nurses and their educators towards more morally and ethically sensitive and reflexively attuned positions around what they talk and write into existence. PMID- 27203581 TI - Multicentric Genome-Wide Association Study for Primary Spontaneous Pneumothorax. AB - Despite elevated incidence and recurrence rates for Primary Spontaneous Pneumothorax (PSP), little is known about its etiology, and the genetics of idiopathic PSP remains unexplored. To identify genetic variants contributing to sporadic PSP risk, we conducted the first PSP genome-wide association study. Two replicate pools of 92 Portuguese PSP cases and of 129 age- and sex-matched controls were allelotyped in triplicate on the Affymetrix Human SNP Array 6.0 arrays. Markers passing quality control were ranked by relative allele score difference between cases and controls (|RASdiff|), by a novel cluster method and by a combined Z-test. 101 single nucleotide polymorphisms (SNPs) were selected using these three approaches for technical validation by individual genotyping in the discovery dataset. 87 out of 94 successfully tested SNPs were nominally associated in the discovery dataset. Replication of the 87 technically validated SNPs was then carried out in an independent replication dataset of 100 Portuguese cases and 425 controls. The intergenic rs4733649 SNP in chromosome 8 (between LINC00824 and LINC00977) was associated with PSP in the discovery (P = 4.07E-03, ORC[95% CI] = 1.88[1.22-2.89]), replication (P = 1.50E-02, ORC[95% CI] = 1.50[1.08-2.09]) and combined datasets (P = 8.61E-05, ORC[95% CI] = 1.65[1.29 2.13]). This study identified for the first time one genetic risk factor for sporadic PSP, but future studies are warranted to further confirm this finding in other populations and uncover its functional role in PSP pathogenesis. PMID- 27203583 TI - Consensus, Dilemmas, and Challenges in Living Donor Liver Transplantation in Latin America. AB - We reviewed the history, volume, outcomes, uniqueness, and challenges of living donor liver transplantation (LDLT) in Latin America. We used the data from the Latin American and Caribbean Transplant Society, local transplant societies, and opinions from local transplant experts. There are more than 160 active liver transplant teams in Latin America, but only 30 centers have used LDLT in the past 2 years. In 2014, 226 LDLTs were done in the region (8.5% of liver transplant activities). Living donor liver transplantation is mainly restricted to pediatric patients. Adult-to-adult LDLT activities decreased after the implementation of the model for end-stage liver disease score and a concomitant increase on the rate of deceased donors per million population. Posttransplant outcome analysis is not mandatory, transparent or regulated in most countries. More experienced teams have outcomes comparable to international expert centers, but donor and recipient morbidity might be underreported. Latin America lags behind in terms of the number of adult LDLT and the rate of living donor utilization in comparison with other continents with similar donation rates. Local alliances and collaborations with major transplant centers in the developed world will contribute to the development of LDLT in Latin America. PMID- 27203584 TI - Paid Living Donation and Growth of Deceased Donor Programs. AB - Limited organ availability in all countries has stimulated discussion about incentives to increase donation. Since 1988, Iran has operated the only government-sponsored paid living donor (LD) kidney transplant program. This article reviews aspects of the Living Unrelated Donor program and development of deceased donation in Iran. Available evidence indicates that in the partially regulated Iranian Model, the direct negotiation between donors and recipients fosters direct monetary relationship with no safeguards against mutual exploitation. Brokers, the black market and transplant tourism exist, and the waiting list has not been eliminated. Through comparison between the large deceased donor program in Shiraz and other centers in Iran, this article explores the association between paid donation and the development of a deceased donor program. Shiraz progressively eliminated paid donor transplants such that by 2011, 85% of kidney transplants in Shiraz compared with 27% across the rest of Iran's other centers were from deceased donors. Among 26 centers, Shiraz undertakes the largest number of deceased donor kidney transplants, most liver transplants, and all pancreas transplants. In conclusion, although many patients with end stage renal disease have received transplants through the paid living donation, the Iranian Model now has serious flaws and is potentially inhibiting substantial growth in deceased donor organ transplants in Iran. PMID- 27203586 TI - Human Kidney Organoids: Nephron Models of Development and Disease. PMID- 27203582 TI - N-terminal Huntingtin Knock-In Mice: Implications of Removing the N-terminal Region of Huntingtin for Therapy. AB - The Huntington's disease (HD) protein, huntingtin (HTT), is a large protein consisting of 3144 amino acids and has conserved N-terminal sequences that are followed by a polyglutamine (polyQ) repeat. Loss of Htt is known to cause embryonic lethality in mice, whereas polyQ expansion leads to adult neuronal degeneration. Whether N-terminal HTT is essential for neuronal development or contributes only to late-onset neurodegeneration remains unknown. We established HTT knock-in mice (N160Q-KI) expressing the first 208 amino acids of HTT with 160Q, and they show age-dependent HTT aggregates in the brain and neurological phenotypes. Importantly, the N-terminal mutant HTT also preferentially accumulates in the striatum, the brain region most affected in HD, indicating the importance of N-terminal HTT in selective neuropathology. That said, homozygous N160Q-KI mice are also embryonic lethal, suggesting that N-terminal HTT alone is unable to support embryonic development. Using Htt knockout neurons, we found that loss of Htt selectively affects the survival of developing neuronal cells, but not astrocytes, in culture. This neuronal degeneration could be rescued by a truncated HTT lacking the first 237 amino acids, but not by N-terminal HTT (1-208 amino acids). Also, the rescue effect depends on the region in HTT known to be involved in intracellular trafficking. Thus, the N-terminal HTT region may not be essential for the survival of developing neurons, but when carrying a large polyQ repeat, can cause selective neuropathology. These findings imply a possible therapeutic benefit of removing the N-terminal region of HTT containing the polyQ repeat to treat the neurodegeneration in HD. PMID- 27203587 TI - Living Donor Liver Transplantation. PMID- 27203588 TI - Lloyd E. Ratner, MD, MPH: Professor of Surgery and Director of Renal & Pancreatic Transplantation at Columbia University, and Treasurer of the American Society of Transplant Surgeons. PMID- 27203590 TI - Living Kidney Donation at a Crossroads: What Steps Do We Need to Take Now? PMID- 27203589 TI - Russell W. Strong, FRCS (Eng), FRACS, FRACDS: Pioneering Live Donor Liver Transplantation. PMID- 27203591 TI - Live Donor Liver Transplantation: An International Perspective. PMID- 27203592 TI - Donor Outcomes in Living Donor Liver Transplantation-Analysis of 275 Donors From a Single Centre in India. AB - BACKGROUND: Live donor liver transplantation is the predominant form of liver transplantation in India and in most Asian countries. Donor outcome reports are an important source of information to be shared with prospective donors at the time of informed consent. This is the first donor outcome series from India. METHODS: Analysis of donor characteristics and morbidity of 275 live donors from a single large volume center is documented. RESULTS: Two hundred seventy-five patients donated from November 2009 to October 2014, 144 were women and 131 were men, 180 donated to adults and 95 donated to children. Right lobe donors were majority at 62.2% followed by left lateral segment 28%. Two thirds of the live donors did not have any morbidity; 114 complications were encountered in 85 patients. The complications were graded as per Clavien 5 tier grading and major morbidity (grade III b, grade IV grade V) was 4.36%. Postoperative biliary complication was seen in 3 donors. CONCLUSIONS: This large single-center study is the first donor outcome report from India, and the results are comparable to other published donor series. Documentation and regular audit of donor outcomes is important to help improve the safety of donor hepatectomy and to provide a database for informed consent of prospective donors. PMID- 27203593 TI - Long-term Outcomes for Living Pancreas Donors in the Modern Era. AB - BACKGROUND: Living donor segmental pancreas transplants (LDSPTx) have been performed selectively to offer a preemptive transplant option for simultaneous pancreas-kidney recipients and to perform a single operation decreasing the cost of pancreas after kidney transplant. For solitary pancreas transplants, this option historically provided a better immunologic match. Although short-term donor outcomes have been documented, there are no long-term studies. METHODS: We studied postdonation outcomes in 46 segmental pancreas living donors. Surgical complications, risk factors (RF) for development of diabetes mellitus (DM) and quality of life were studied. A risk stratification model (RSM) for DM was created using predonation and postdonation RFs. Recipient outcomes were analyzed. RESULTS: Between January 1, 1994 and May 1, 2013, 46 LDSPTx were performed. Intraoperatively, 5 (11%) donors received transfusion. Overall, 9 (20%) donors underwent splenectomy. Postoperative complications included: 6 (13%) peripancreatic fluid collections and 2 (4%) pancreatitis episodes. Postdonation, DM requiring oral hypoglycemics was diagnosed in 7 (15%) donors and insulin dependent DM in 5 (11%) donors. RSM with three predonation RFs (oral glucose tolerance test, basal insulin, fasting plasma glucose) and 1 postdonation RF, greater than 15% increase in body mass index from preoperative (Delta body mass index >15), predicted 12 (100%) donors that developed postdonation DM. Quality of life was not significantly affected by donation. Mean graft survival was 9.5 (+/ 4.4) years from donors without and 9.6 (+/-5.4) years from donors with postdonation DM. CONCLUSIONS: LDSPTx can be performed with good recipient outcomes. The donation is associated with donor morbidity including impaired glucose control. Donor morbidity can be minimized by using RSM and predonation counseling on life style modifications postdonation. PMID- 27203594 TI - Video game players show higher performance but no difference in speed of attention shifts. AB - Video games have become both a widespread leisure activity and a substantial field of research. In a variety of tasks, video game players (VGPs) perform better than non-video game players (NVGPs). This difference is most likely explained by an alteration of the basic mechanisms underlying visuospatial attention. More specifically, the present study hypothesizes that VGPs are able to shift attention faster than NVGPs. Such alterations in attention cannot be disentangled from changes in stimulus-response mappings in reaction time based measurements. Therefore, we used a spatial cueing task with varying cue lead times (CLTs) to investigate the speed of covert attention shifts of 98 male participants divided into 36 NVGPs and 62 VGPs based on their weekly gaming time. VGPs exhibited higher peak and mean performance than NVGPs. However, we did not find any differences in the speed of covert attention shifts as measured by the CLT needed to achieve peak performance. Thus, our results clearly rule out faster stimulus-response mappings as an explanation for the higher performance of VGPs in line with previous studies. More importantly, our data do not support the notion of faster attention shifts in VGPs as another possible explanation. PMID- 27203595 TI - Estimating Causal Effects of Local Air Pollution on Daily Deaths: Effect of Low Levels. AB - BACKGROUND: Although many time-series studies have established associations of daily pollution variations with daily deaths, there are fewer at low concentrations, or focused on locally generated pollution, which is becoming more important as regulations reduce regional transport. Causal modeling approaches are also lacking. OBJECTIVE: We used causal modeling to estimate the impact of local air pollution on mortality at low concentrations. METHODS: Using an instrumental variable approach, we developed an instrument for variations in local pollution concentrations that is unlikely to be correlated with other causes of death, and examined its association with daily deaths in the Boston, Massachusetts, area. We combined height of the planetary boundary layer and wind speed, which affect concentrations of local emissions, to develop the instrument for particulate matter <= 2.5 MUm (PM2.5), black carbon (BC), or nitrogen dioxide (NO2) variations that were independent of year, month, and temperature. We also used Granger causality to assess whether omitted variable confounding existed. RESULTS: We estimated that an interquartile range increase in the instrument for local PM2.5 was associated with a 0.90% increase in daily deaths (95% CI: 0.25, 1.56). A similar result was found for BC, and a weaker association with NO2. The Granger test found no evidence of omitted variable confounding for the instrument. A separate test confirmed the instrument was not associated with mortality independent of pollution. Furthermore, the association remained when all days with PM2.5 concentrations > 30 MUg/m3 were excluded from the analysis (0.84% increase in daily deaths; 95% CI: 0.19, 1.50). CONCLUSIONS: We conclude that there is a causal association of local air pollution with daily deaths at concentrations below U.S. EPA standards. The estimated attributable risk in Boston exceeded 1,800 deaths during the study period, indicating that important public health benefits can follow from further control efforts. Citation: Schwartz J, Bind MA, Koutrakis P. 2017. Estimating causal effects of local air pollution on daily deaths: effect of low levels. Environ Health Perspect 125:23 29; http://dx.doi.org/10.1289/EHP232. PMID- 27203596 TI - Evaluation of interaction between imidazolium-based chloride ionic liquids and calf thymus DNA. AB - With ionic liquids (ILs) being widely used, the toxicity of many ILs has been studied and verified. However the mechanism underlying the interaction between ILs and DNA needs to be investigated. In this study, the interaction of three imidazolium-based ILs ([C8mim]Cl, [C12mim]Cl, and [C16mim]Cl) with calf thymus DNA (ctDNA) was investigated by UV absorption spectroscopy and fluorescence spectroscopy. An intense interaction between [Cnmim]Cl and ctDNA was observed, involving a hypochromic effect or even a hyperchromic effect, in the UV absorption spectrum of ctDNA at 260nm. The Tm of ctDNA increased over 10 degrees C after binding with [Cnmim]Cl, and the KSV values of [Cnmim]Cl-ctDNA quenched by potassium iodide (KI) were lower than those of [Cnmim]Cl. The fluorescence intensity of ctDNA-ethidium bromide (EB) was gradually quenched as the [Cnmim]Cl concentration increased. The results indicated that ctDNA interacted with [Cnmim]Cl through an intercalation binding mode. The mechanism of fluorescence quenching of [Cnmim]Cl with ctDNA involved static quenching. The binding constant between [Cnmim]Cl and ctDNA were 1443, 11169, and 67189, and the number of binding sites were 0.89, 1.10, and 1.27 at 298K, for [C8mim]Cl, [C12mim]Cl, and [C16mim]Cl, respectively. The results indicated that the intercalation binding between the three [Cnmim]Cl and ctDNA increased with increasing IL-alkyl chain length. These results will aid in the understanding of the mechanism of toxicity and of the biologically mediated environmental processes of ILs. PMID- 27203597 TI - How Hinge Positioning in Cross-Country Ski Bindings Affect Exercise Efficiency, Cycle Characteristics and Muscle Coordination during Submaximal Roller Skiing. AB - The purposes of the current study were to 1) test if the hinge position in the binding of skating skis has an effect on gross efficiency or cycle characteristics and 2) investigate whether hinge positioning affects synergistic components of the muscle activation in six lower leg muscles. Eleven male skiers performed three 4-min sessions at moderate intensity while cross-country ski skating and using a klapskate binding. Three different positions were tested for the binding's hinge, ranging from the front of the first distal phalange to the metatarsal-phalangeal joint. Gross efficiency and cycle characteristics were determined, and the electromyographic (EMG) signals of six lower limb muscles were collected. EMG signals were wavelet transformed, normalized, joined into a multi-dimensional vector, and submitted to a principle component analysis (PCA). Our results did not reveal any changes to gross efficiency or cycle characteristics when altering the hinge position. However, our EMG analysis found small but significant effects of hinge positioning on muscle coordinative patterns (P < 0.05). The changed patterns in muscle activation are in alignment with previously described mechanisms that explain the effects of hinge positioning in speed-skating klapskates. Finally, the within-subject results of the EMG analysis suggested that in addition to the between-subject effects, further forms of muscle coordination patterns appear to be employed by some, but not all participants. PMID- 27203599 TI - Trajectories of Metabolic Risk Factors and Biochemical Markers prior to the Onset of Cardiovascular Disease - The Doetinchem Cohort Study. AB - Risk factors often develop at young age and are maintained over time, but it is not fully understood how risk factors develop over time preceding cardiovascular disease (CVD). Our objective was to examine how levels and trajectories of metabolic risk factors and biochemical markers prior to diagnosis differ between people with and without CVD over a period of up to 15-20 years. A total of 449 incident non-fatal and fatal CVD cases and 1,347 age- and sex-matched controls were identified in a prospective cohort between 1993 and 2011. Metabolic risk factors and biochemical markers were measured at five-year intervals prior to diagnosis. Trajectories of metabolic risk factors and biochemical markers were analysed using random coefficient analyses. Although not always statistically significant, participants with CVD had slightly more unfavourable levels for most metabolic risk factors and biochemical markers 15-20 years before diagnosis than controls. Subsequent trajectories until diagnosis were similar in participants with incident CVD and controls for body mass index, diastolic blood pressure, total cholesterol, HDL cholesterol, random glucose, triglycerides, gamma glutamyltransferase, C-reactive protein and uric acid. Trajectories were more unfavourable in participants with CVD than controls for systolic blood pressure, waist circumference and estimated glomerular filtration rate (p<=0.05). For example, among participants with CVD, systolic blood pressure increased on average by 9 mmHg over the 18-year period preceding diagnosis, whereas the increase among controls was 4 mmHg. In conclusion, unfavourable levels of metabolic risk factors and biochemical markers are present long before CVD, which indicates that the risk of CVD is already partly determined in young adulthood. This underscores the need for early prevention to reduce the burden of CVD. PMID- 27203598 TI - Rab11 and Lysotracker Markers Reveal Correlation between Endosomal Pathways and Transfection Efficiency of Surface-Functionalized Cationic Liposome-DNA Nanoparticles. AB - Cationic liposomes (CLs) are widely studied as carriers of DNA and short interfering RNA for gene delivery and silencing, and related clinical trials are ongoing. Optimization of transfection efficiency (TE) requires understanding of CL-nucleic acid nanoparticle (NP) interactions with cells, NP endosomal pathways, endosomal escape, and events leading to release of active nucleic acid from the lipid carrier. Here, we studied endosomal pathways and TE of surface functionalized CL-DNA NPs in PC-3 prostate cancer cells displaying overexpressed integrin and neuropilin-1 receptors. The NPs contained RGD-PEG-lipid or RPARPAR PEG-lipid, targeting integrin, and neuropilin-1 receptors, respectively, or control PEG-lipid. Fluorescence colocalization using Rab11-GFP and Lysotracker enabled simultaneous colocalization of NPs with recycling endosome (Rab11) and late endosome/lysosome (Rab7/Lysotracker) pathways at increasing mole fractions of pentavalent MVL5 (+5 e) at low (10 mol %), high (50 mol %), and very high (70 mol %) membrane charge density (sigmaM). For these cationic NPs (lipid/DNA molar charge ratio, rhochg = 5), the influence of membrane charge density on pathway selection and transfection efficiency is similar for both peptide-PEG NPs, although, quantitatively, the effect is larger for RGD-PEG compared to RPARPAR PEG NPs. At low sigmaM, peptide-PEG NPs show preference for the recycling endosome over the late endosome/lysosome pathway. Increases in sigmaM, from low to high, lead to decreases in colocalization with recycling endosomes and simultaneous increases in colocalization with the late endosome/lysosome pathway. Combining colocalization and functional TE data at low and high sigmaM shows that higher TE correlates with a larger fraction of NPs colocalized with the late endosome/lysosome pathway while lower TE correlates with a larger fraction of NPs colocalized with the Rab11 recycling pathway. The findings lead to a hypothesis that increases in sigmaM, leading to enhanced late endosome/lysosome pathway selection and higher TE, result from increased nonspecific electrostatic attractions between NPs and endosome luminal membranes, and conversely, enhanced recycling pathway for NPs and lower TE are due to weaker attractions. Surprisingly, at very high sigmaM, the inverse relation between the two pathways observed at low and high sigmaM breaks down, pointing to a more complex NP pathway behavior. PMID- 27203601 TI - Early effects of Roux-en-Y gastric bypass on peptides and hormones involved in the control of energy balance. AB - INTRODUCTION: Body weight varies depending on the prevailing direction of environmental pressures; however, physiological factors also play a significant role in the control of body weight. The aim of the present study was to assess the impact of Roux-en-Y gastric bypass (RYGB) on hormones and peptides involved in the control of energy balance and their possible implications in appetite/satiety. METHODS: The sample included 39 individuals with extreme obesity (37 women and two men) who underwent RYGB. Anthropometric and biochemical markers were collected before surgery and 6 months after RYGB. RESULTS: The BMI decreased from 44.3+/-6.4 to 31.7+/-5.7 kg/m (P<0.001) at the sixth month. Percentage of excess weight lost was 63.2+/-25.0%. Leptin and glucose levels decreased significantly 6 months after RYGB (P<0.001). Interestingly, a significant correlation was confirmed between the anorexigenic gut hormone peptide YY (PYY) and the central anorexigenic mediator alpha-melanocyte stimulating hormone after 6 months of RYGB (r=0.35, P=0.004). In contrast, PYY concentrations were correlated negatively with BMI (r=-0.34, P=0.002). CONCLUSION: In the present investigation, it was found that there is a relationship between alpha-melanocyte-stimulating hormone and PYY concentrations, and it supports the role of the PYY to POMC signal in appetite regulation after RYGB. PMID- 27203600 TI - Lateralized Resting-State Functional Brain Network Organization Changes in Heart Failure. AB - Heart failure (HF) patients show brain injury in autonomic, affective, and cognitive sites, which can change resting-state functional connectivity (FC), potentially altering overall functional brain network organization. However, the status of such connectivity or functional organization is unknown in HF. Determination of that status was the aim here, and we examined region-to-region FC and brain network topological properties across the whole-brain in 27 HF patients compared to 53 controls with resting-state functional MRI procedures. Decreased FC in HF appeared between the caudate and cerebellar regions, olfactory and cerebellar sites, vermis and medial frontal regions, and precentral gyri and cerebellar areas. However, increased FC emerged between the middle frontal gyrus and sensorimotor areas, superior parietal gyrus and orbito/medial frontal regions, inferior temporal gyrus and lingual gyrus/cerebellar lobe/pallidum, fusiform gyrus and superior orbitofrontal gyrus and cerebellar sites, and within vermis and cerebellar areas; these connections were largely in the right hemisphere (p<0.005; 10,000 permutations). The topology of functional integration and specialized characteristics in HF are significantly changed in regions showing altered FC, an outcome which would interfere with brain network organization (p<0.05; 10,000 permutations). Brain dysfunction in HF extends to resting conditions, and autonomic, cognitive, and affective deficits may stem from altered FC and brain network organization that may contribute to higher morbidity and mortality in the condition. Our findings likely result from the prominent axonal and nuclear structural changes reported earlier in HF; protecting neural tissue may improve FC integrity, and thus, increase quality of life and reduce morbidity and mortality. PMID- 27203602 TI - Effect of psychosocial stressors on patients with Crohn's disease: threatening life experiences and family relations. AB - BACKGROUND AND AIMS: Threatening life experiences and adverse family relations are major psychosocial stressors affecting mental and physical health in chronic illnesses, but their influence in Crohn's disease (CD) is unclear. We assessed whether these stressors would predict the psychological and medical condition of CD patients. METHODS: Consecutive adult CD patients completed a series of instruments including demography, Patient Harvey-Bradshaw Index (P-HBI), Short Inflammatory Bowel Disease Questionnaire (SIBDQ), short-form survey instrument (SF-36), brief symptom inventory (BSI), family assessment device (FAD), and list of threatening life experiences (LTE). Associations of FAD and LTE with P-HBI, SIBDQ, SF-36, and BSI were examined by multiple linear and quantile regression analyses. RESULTS: The cohort included 391 patients, mean age 38.38+/-13.95 years, 59.6% women, with intermediate economic status. The median scores were as follows: P-HBI 4 (2-8), FAD 1.67 (1.3-2.1), LTE 1 (0-3), SF-36 physical health 43.75 (33.7-51.0), SF-36 mental health 42.99 (34.1-51.9), and BSI-Global Severity Index 0.81 (0.4-1.4). The SIBDQ was 47.27+/-13.9. LTE was associated with increased P-HBI in all quantiles and FAD in the 50% quantile. FAD and LTE were associated with reduced SIBDQ (P<0.001). Higher LTE was associated with lower SF 36 physical and mental health (P<0.001); FAD was associated with reduced mental health (P<0.001). FAD and LTE were associated positively with GSI in all quantiles; age was associated negatively. CONCLUSION: CD patients with more threatening life experiences and adverse family relations were less healthy both physically and mentally. Physicians offering patients sociopsychological therapy should relate to threatening life experiences and family relations. PMID- 27203604 TI - The History of Treatment of Twin-to-Twin Transfusion Syndrome. AB - Historical suggestions of twin-to-twin transfusion syndrome (TTTS) date back to the early 17th century. Placental anastomoses were first reported in 1687; however, it was Schatz who first identified their importance in 1875. He recognized 'the area of transfusion' within the 'villous district' of the placenta, which he named the 'third circulation'. This article describes how the management of TTTS has evolved as we have gained a more sophisticated understanding and appreciation of the complex vascular anastomoses that exist in monochorionic twin placentae. Currently, fetosopic laser occlusion is the preferred treatment option for TTTS. PMID- 27203603 TI - Editorial-Special Issue. AB - Monochorionic twin pregnancies are subject to unique complications that can threaten the life and well-being of both fetuses, resulting in a disproportionate increase in perinatal morbidity and mortality. PMID- 27203605 TI - Twin-to-Twin Transfusion Syndrome: Definition, Staging, and Ultrasound Assessment. AB - OBJECTIVE: The purpose of this article is to review the definition of twin-to twin transfusion syndrome (TTTS) and the sonographic diagnostic assessment of these cases prior to therapy. MATERIALS AND METHODS: The article addresses the terminology used to refer to the condition and describes the systematic ultrasound assessment of the condition, including the ultrasound diagnosis, the staging of the disease, cervical assessment and pre-operative mapping. RESULTS: From an etymologic and medical point of view, the term 'fetofetal transfusion' is more appropriate than 'TTTS'. However, as the latter, and its attendant acronym TTTS, have been widely adopted in the English language, it is impractical to change at this point. TTTS is defined sonographically in the combined presence of a maximum vertical pocket (MVP) of 8 cm or greater in one sac and 2 cm or less in the other sac, regardless of the gestational age at diagnosis. Staging of the condition using the Quintero staging system is practical, reproducible, and accepted. Transvaginal cervical length assessment should be an integral part of the ultrasound evaluation. Pre-operative mapping to anticipate the location of the placental vascular anastomoses and avoid injuring the dividing membrane is also discussed. CONCLUSIONS: The term 'TTTS' can continue to be used in the English medical literature. The condition can be diagnosed and assessed following a systematic ultrasound methodology. The use of such ultrasound methodology breaks the examination into a distinct set of components, assuring a comprehensive examination and proper communication among caregivers. PMID- 27203606 TI - Laser Treatment of Twin-to-Twin Transfusion Syndrome. AB - OBJECTIVE: Laser ablation of all placental vascular anastomoses is the optimal treatment for twin-twin transfusion syndrome (TTTS). However, two important controversies are apparent in the literature: (a) a gap between concept and performance, and (b) controversy regarding whether all the anastomoses can be identified endoscopically and whether blind lasering of healthy placenta is justified. The purpose of this article is: (a) to address the potential source of the gap between concept and performance by analyzing the fundamental steps needed to successfully accomplish the surgery, and (b) to discuss the resulting competency benchmarks reported with the different surgical techniques. MATERIALS AND METHODS: Laser surgery for TTTS can be broken down into two fundamental steps: (1) endoscopic identification of the placental vascular anastomoses, (2) laser ablation of the anastomoses. The two steps are not synonymous: (a) regarding the endoscopic identification of the anastomoses, the non-selective technique is based upon lasering all vessels crossing the dividing membrane, whether anastomotic or not. The selective technique identifies and lasers only placental vascular anastomoses. The Solomon technique is based on the theory that not all anastomoses are endoscopically visible and thus involves lasering healthy areas of the placenta between lasered anastomoses, (b) regarding the actual laser ablation of the anastomoses, successful completion of the surgery (i.e., lasering all the anastomoses) can be measured by the rate of persistent or reverse TTTS (PRTTTS) and how often a selective technique can be achieved. Articles representing the different techniques are discussed. RESULTS: The non-selective technique is associated with the lowest double survival rate (35%), compared with 60-75% of the Solomon or the Quintero selective techniques. The Solomon technique is associated with a 20% rate of residual patent placental vascular anastomoses, compared to 3.5-5% for the selective technique (p < .05). Both the Solomon and the selective technique are associated with a 1% risk of PRTTTS. Adequate placental assessment is highest with the selective technique (99%) compared with the Solomon (80%) or the 'standard' (60%) techniques (p < .05). A surgical performance index is proposed. CONCLUSION: The Quintero selective technique was associated with the highest rate of successful ablation and lowest rate of PRTTTS. The Solomon technique represents a historical backward movement in the identification of placental vascular anastomoses and is associated with higher rate of residual patent vascular communications. The reported outcomes of the Quintero selective technique do not lend support to the existence of invisible anastomoses or justify lasering healthy placental tissue. PMID- 27203607 TI - Solomon Technique Versus Selective Coagulation for Twin-Twin Transfusion Syndrome. AB - Monochorionic twin pregnancies can be complicated by twin-to-twin transfusion syndrome (TTTS). The best treatment option for TTTS is fetoscopic laser coagulation of the vascular anastomoses between donor and recipient. After laser therapy, up to 33% residual anastomoses were seen. These residual anastomoses can cause twin anemia polycythemia sequence (TAPS) and recurrent TTTS. In order to reduce the number of residual anastomoses and their complications, a new technique, the Solomon technique, where the whole vascular equator will be coagulated, was introduced. The Solomon technique showed a reduction of recurrent TTS compared to the selective technique. The incidence of recurrent TTTS after the Solomon technique ranged from 0% to 3.9% compared to 5.3-8.5% after the selective technique. The incidence of TAPS after the Solomon technique ranged from 0% to 2.9% compared to 4.2-15.6% after the selective technique. The Solomon technique may improve dual survival rates ranging from 64% to 85% compared to 46 76% for the selective technique. There was no difference reported in procedure related complications such as intrauterine infection and preterm premature rupture of membranes. The Solomon technique significantly reduced the incidence of TAPS and recurrent TTTS and may improve survival and neonatal outcome, without identifiable adverse outcome or complications; therefore, the Solomon technique is recommended for the treatment of TTTS. PMID- 27203608 TI - Fetal Brain Injury in Survivors of Twin Pregnancies Complicated by Demise of One Twin: A Review. AB - Perinatal mortality is increased considerably in multiple pregnancies compared to singleton pregnancies, with single intrauterine fetal demise (sIUFD) presenting a rare but unique perinatal problem. Monochorionic pregnancies are at particular risk of sIUFD due to bidirectional inter-twin placental vascular anastomoses. The resulting inter-twin blood flow can become unbalanced, causing acute and chronic inter-twin transfusion and profound anemia secondary to fetal exsanguination into the low-pressure circulation of the dead fetus. If the sIUFD occurs after 14 weeks' gestation it is believed to have the most significant effect on the continuing pregnancy as the co-twin is at increased risk of preterm delivery, long-term neurological complications, and death. This article will focus on fetal brain injury in the surviving co-twin in the case of sIUFD, as it is the most common kind of injury in sIUFD, and one which concerns parents and may be the basis for terminating the pregnancy. We will outline how these brain injuries are thought to occur and describe potential pathophysiological mechanisms. We will discuss risk factors for brain injury in cases of sIUFD, including: chorionicity, cause of the sIUFD (spontaneous or secondary to an underlying pathological process such as twin-to-twin transfusion syndrome), gestation of delivery and how to prevent brain injury in the co-twin. We also review modes of imaging, discuss the difficulties in predicting the long-term outcome for co-twin survivors, and highlight the dearth of research in this area. PMID- 27203611 TI - Thermodynamic Self-Limiting Growth of Heteroepitaxial Islands Induced by Nonlinear Elastic Effect. AB - We investigate nonlinear elastic effect (NLEF) on the growth of heteroepitaxial islands, a topic of both scientific and technological significance for their applications as quantum dots. We show that the NLEF induces a thermodynamic self limiting growth mechanism that hinders the strain relaxation of coherent island beyond a maximum size, which is in contrast to indefinite strain relaxation with increasing island size in the linear elastic regime. This self-limiting growth effect shows a strong dependence on the island facet angle, which applies also to islands inside pits patterned in a substrate surface with an additional dependence on the pit inclination angle. Consequently, primary islands nucleate and grow first in the pits and then secondary islands nucleate at the rim around the pits after the primary islands reach the self-limited maximum size. Our theory sheds new lights on understanding the heteroepitaxial island growth and explains a number of past and recent experimental observations. PMID- 27203612 TI - "Silent Sinus Syndrome" Following Orbital Trauma: A Case Series and Review of the Literature. AB - PURPOSE: To describe the demographics, presentation, and treatment of "silent sinus syndrome" (SSS) diagnosed following orbital trauma and review the literature on this topic. METHODS: A retrospective review of 6 consecutive cases of SSS following trauma seen by the authors from 2004 to 2015. Data collected included patient demographics, details of previous trauma, clinical presentation, imaging findings, surgery performed, outcome, and follow up. RESULTS: Six patients were identified presenting with SSS following orbital floor fracture. All cases developed progressive enophthalmos due to maxillary sinus atelectasis on average 8 months after their initial trauma (range, 3-16 months). The appearance of the maxillary sinus on CT was indistinguishable from the changes seen in spontaneous SSS. All 6 patients had surgical repair, which included maxillary sinus reventilation and surgery to build up the orbital floor and correct the enophthalmos in 4 patients, maxillary sinus reventilation surgery only in 1 patient and surgery to build up the orbital floor only in 1 patient. There was a reduction of enophthalmos and globe dystopia in all cases with no significant complications. CONCLUSIONS: Changes in the maxillary sinus after orbital floor fracture may occur in the months following the initial trauma and the changes are indistinguishable from those seen in spontaneous SSS. The mechanism is presumed to be obstruction of the natural ostium of the maxillary sinus, accumulation of secretions and the development of negative pressure within the sinus leading to its collapse. PMID- 27203614 TI - The Author File: Markus Sauer. PMID- 27203613 TI - Giant Chondroid Syringoma of the Lower Eyelid. AB - Chondroid syringoma is a benign mixed tumor characterized by sweat gland elements in a cartilaginous stroma. This rare tumor accounts for only 0.01% of all primary skin tumors and occurs only rarely in the periorbital region. Usually between 0.5 cm and 3.0 cm, risk of malignancy increases in chondroid syringomas greater than 3.0 cm in size. Here, the authors report a rare case of giant chondroid syringoma arising in the lower eyelid, characterized by keratinized stratified epithelium in a cartilaginous stroma. This case illustrates the importance of considering a possible diagnosis of chondroid syringoma in the evaluation of eyelid masses. PMID- 27203617 TI - Imaging free radicals in organelles, cells, tissue, and in vivo with immuno-spin trapping. AB - The accurate and sensitive detection of biological free radicals in a reliable manner is required to define the mechanistic roles of such species in biochemistry, medicine and toxicology. Most of the techniques currently available are either not appropriate to detect free radicals in cells and tissues due to sensitivity limitations (electron spin resonance, ESR) or subject to artifacts that make the validity of the results questionable (fluorescent probe-based analysis). The development of the immuno-spin trapping technique overcomes all these difficulties. This technique is based on the reaction of amino acid- and DNA base-derived radicals with the spin trap 5, 5-dimethyl-1-pyrroline N-oxide (DMPO) to form protein- and DNA-DMPO nitroxide radical adducts, respectively. These adducts have limited stability and decay to produce the very stable macromolecule-DMPO-nitrone product. This stable product can be detected by mass spectrometry, NMR or immunochemistry by the use of anti-DMPO nitrone antibodies. The formation of macromolecule-DMPO-nitrone adducts is based on the selective reaction of free radical addition to the spin trap and is thus not subject to artifacts frequently encountered with other methods for free radical detection. The selectivity of spin trapping for free radicals in biological systems has been proven by ESR. Immuno-spin trapping is proving to be a potent, sensitive (a million times higher sensitivity than ESR), and easy (not quantum mechanical) method to detect low levels of macromolecule-derived radicals produced in vitro and in vivo. Anti-DMPO antibodies have been used to determine the distribution of free radicals in cells and tissues and even in living animals. In summary, the invention of the immuno-spin trapping technique has had a major impact on the ability to accurately and sensitively detect biological free radicals and, subsequently, on our understanding of the role of free radicals in biochemistry, medicine and toxicology. PMID- 27203618 TI - Effect of Ambient Temperature on Total Organic Gas Speciation Profiles from Light Duty Gasoline Vehicle Exhaust. AB - Total organic gases (TOG) emissions from motor vehicles include air toxic compounds and contribute to formation of ground-level ozone and secondary organic aerosol (SOA). These emissions are known to be affected by temperature; however previous studies have typically focused only on the temperature dependence of total emission factors and select toxic compounds. This study builds on the previous research by performing an evaluation of a comprehensive set of gas-phase organic compounds present in gasoline motor vehicle exhaust. A fleet of five vehicles using port fuel injection engine technology and running on E10 fuel was tested. Overall, three temperatures (0, 20, and 75 degrees F; or -18, -7, and 24 degrees C), two driving conditions (urban-FTP75 and aggressive driving-US06) and 161 compounds were evaluated; the emissions distributions were used to construct speciation profiles for each driving cycle and temperature. Overall, the speciation results indicated a significant increase in alkane and methane content, and decrease in alcohol, aldehyde and ketone content with decreasing temperature. These were verified using a statistical significance test. The fraction and composition of Mobile Source Air Toxics (MSATs) were significantly affected by temperature for both driving cycles. The ozone forming potentials of these profiles were evaluated using the maximum incremental reactivity (MIR) scale. Aromatic content was predicted to be a major driver behind the ozone forming potentials. Additionally, the decreasing ozone potential could be attributed to increased methane fractions with increasing temperature. PMID- 27203619 TI - Cytoskeletal control of axon domain assembly and function. AB - Neurons are organized and connected into functional circuits by axons that conduct action potentials. Many vertebrate axons are myelinated and further subdivided into excitable domains that include the axon initial segment (AIS) and nodes of Ranvier. Nodes of Ranvier regenerate and propagate action potentials, while AIS regulate action potential initiation and neuronal polarity. Two distinct cytoskeletons control axon structure and function: 1) a submembranous ankyrin/spectrin cytoskeleton that clusters ion channels and provides mechanical support, and 2) a microtubule-based cytoskeleton that controls selective trafficking of dendritic and axonal cargoes. Here, we review recent studies that provide significant additional insight into the cytoskeleton-dependent mechanisms controlling the functional organization of axons. PMID- 27203621 TI - Characterizing proton-activated materials to develop PET-mediated proton range verification markers. AB - Conventional proton beam range verification using positron emission tomography (PET) relies on tissue activation alone and therefore requires particle therapy PET whose installation can represent a large financial burden for many centers. Previously, we showed the feasibility of developing patient implantable markers using high proton cross-section materials ((18)O, Cu, and (68)Zn) for in vivo proton range verification using conventional PET scanners. In this technical note, we characterize those materials to test their usability in more clinically relevant conditions. Two phantoms made of low-density balsa wood (~0.1 g cm(-3)) and beef (~1.0 g cm(-3)) were embedded with Cu or (68)Zn foils of several volumes (10-50 mm(3)). The metal foils were positioned at several depths in the dose fall off region, which had been determined from our previous study. The phantoms were then irradiated with different proton doses (1-5 Gy). After irradiation, the phantoms with the embedded foils were moved to a diagnostic PET scanner and imaged. The acquired data were reconstructed with 20-40 min of scan time using various delay times (30-150 min) to determine the maximum contrast-to-noise ratio. The resultant PET/computed tomography (CT) fusion images of the activated foils were then examined and the foils' PET signal strength/visibility was scored on a 5 point scale by 13 radiologists experienced in nuclear medicine. For both phantoms, the visibility of activated foils increased in proportion to the foil volume, dose, and PET scan time. A linear model was constructed with visibility scores as the response variable and all other factors (marker material, phantom material, dose, and PET scan time) as covariates. Using the linear model, volumes of foils that provided adequate visibility (score 3) were determined for each dose and PET scan time. The foil volumes that were determined will be used as a guideline in developing practical implantable markers. PMID- 27203623 TI - Corrigendum: Length of intact plasma membrane determines the diffusion properties of cellular water. PMID- 27203622 TI - Rumination and postnatal depression: A systematic review and a cognitive model. AB - Postnatal depression (PND) confers risk for a range of negative child developmental outcomes, at least in part through its impact on parenting behaviour. Whilst the behavioural effects of depression on parenting are well established, the cognitive mechanisms that may mediate this effect are less well understood. The current paper proposes that rumination may be a key cognitive mechanism through which parenting is affected in PND, and provides a systematic review of the existing literature on rumination in the context of perinatal depression. The review identifies ten relevant papers. Eight are questionnaire based studies examining the role of rumination in predicting future depression and/or mother-infant relationship outcomes, such as bonding. Two are experimental studies examining the effects of induced rumination on parenting behaviours. The results of the review are discussed, and remaining questions highlighted. We then present a new theoretical model, developed specifically for the perinatal context, and informed by existing models of rumination and worry. Our cognitive model emphasises the relationship between rumination, cognitive biases and cognitive control, and the impact of these variables on infant cue processing and subsequent parenting responses. The model provides a potential framework for future work in this area, and to guide the development of treatment interventions. PMID- 27203625 TI - Revised Damping Parameters for the D3 Dispersion Correction to Density Functional Theory. AB - Since the original fitting of Grimme's DFT-D3 damping parameters, the number and quality of benchmark interaction energies has increased significantly. Here, conventional benchmark sets, which focus on minimum-orientation radial curves at the expense of angular diversity, are augmented by new databases such as side chain-side chain interactions (SSI), which are composed of interactions gleaned from crystal data and contain no such minima-focused bias. Moreover, some existing databases such as S22*5 are extended to shorter intermolecular separations. This improved DFT-D3 training set provides a balanced description of distances, covers the entire range of interaction types, and at 1526 data points is far larger than the original training set of 130. The results are validated against a new collection of 6773 data points and demonstrate that the effect of refitting the damping parameters ranges from no change in accuracy (LC-omegaPBE D3) to an almost 2-fold decrease in average error (PBE-D3). PMID- 27203626 TI - Theoretical Study of Tetrahydrofuran-Stabilized Al13 Superatom Cluster. AB - We present here an in-depth study upon the interaction between a neutral cluster Al13 and a typical ligand tetrahydrofuran (THF) via density functional theory (DFT) calculation. It is found that electron delocalization over the framework of Al13 and THF facilitates ligand-to-Al13 charge transfer leading to enhanced stability for the superhalogen cluster Al13. Further study on the stabilization of Al13(THF)n cluster complexes with n = 1-8 reveals that the adsorption of more THF ligands gradually enhances the total binding energy and the total electronic charge transfer from the ligand to Al13. The bonding nature and stabilization of Al13(THF)n cluster are then demonstrated by rationalizing the interactions between superatomic and molecular orbitals of Al13 and THF, respectively. PMID- 27203624 TI - Actinomycosis after allogeneic hematopoietic stem cell transplantation despite penicillin prophylaxis. AB - Actinomycosis is a rare chronic and multifaceted disease caused by Actinomyces species frequently mimicking malignancy or other chronic granulomatous lung diseases. We report 4 original presentations of actinomycosis arising under supposed penicillin prophylaxis in allogeneic stem cell transplantation recipients. PMID- 27203627 TI - Sparse regularization for EIT reconstruction incorporating structural information derived from medical imaging. AB - Electrical impedance tomography (EIT) reconstructs the conductivity distribution of a domain using electrical data on its boundary. This is an ill-posed inverse problem usually solved on a finite element mesh. For this article, a special regularization method incorporating structural information of the targeted domain is proposed and evaluated. Structural information was obtained either from computed tomography images or from preliminary EIT reconstructions by a modified k-means clustering. The proposed regularization method integrates this structural information into the reconstruction as a soft constraint preferring sparsity in group level. A first evaluation with Monte Carlo simulations indicated that the proposed solver is more robust to noise and the resulting images show fewer artifacts. This finding is supported by real data analysis. The structure based regularization has the potential to balance structural a priori information with data driven reconstruction. It is robust to noise, reduces artifacts and produces images that reflect anatomy and are thus easier to interpret for physicians. PMID- 27203628 TI - Assessing the Presence and Severity of Constipation with Plain Radiographs in Constipated Palliative Care Patients. AB - BACKGROUND: Palliative care guidelines recommend plain radiographs to assess constipation based on the presumption that visible fecal shadowing represents stool retention. Despite this, using plain radiographs in this way is not well validated. OBJECTIVES: This work's main aim was to compare clinicians' reports of fecal loading on radiographs. This study also compares clinicians' assessments with radio-opaque marker transit studies and patients' self-reported constipation symptoms. METHODS: This study was conducted in a sample of 30 constipated palliative care patients taking laxatives who had all undergone colon transit studies and contemporaneous assessment of constipation symptoms with the Patient Assessment of Constipation Symptom (PAC-SYM) questionnaire. Four separate clinicians independently reported their opinions of fecal loading using a previously developed fecal loading scale. Participant details were summarized and pair-wise inter-rater agreement among all four raters were examined using the Bland-Altman approach. For the comparisons of the clinician-assigned fecal loading score between the radiographic assessment of the normal and slow colon transit time, the nonparametric approach of Mann-Whitney U tests were applied. Spearman's correlation analyses were employed to investigate the association between the clinician-assigned fecal loading score and the patient self-reported PAC-SYM score. RESULTS: The results of this study are very similar to other studies conducted in functional constipation, highlighting systematic disagreement between observers. Further poor correlations were noted between fecal loading scores and colon transit times and with patient self-reported symptoms. CONCLUSION: These results, when considered with other work in chronic constipation, question the ongoing use of radiographs in the diagnosis of constipation. PMID- 27203629 TI - US health care: plumbing the depths of disparities. PMID- 27203630 TI - No free expression, no health. PMID- 27203631 TI - Australia's offshore refugee policy in disarray. PMID- 27203632 TI - Treating giant-cell arteritis: is IL-6 the cytokine to target? PMID- 27203633 TI - Mind the gap: jumping from vaccine licensure to routine use. PMID- 27203635 TI - Making the case for supervised injection services. PMID- 27203637 TI - Canada debates medically assisted dying law. PMID- 27203639 TI - Concern over deteriorating rights situation in Egypt. PMID- 27203638 TI - Countries mull over incentives for developing antibiotics. PMID- 27203642 TI - Jim Smith: biologist at the heart of embryonic Francis Crick Institute. PMID- 27203643 TI - Could you wait a second? PMID- 27203644 TI - Yvette Fay Francis-McBarnette. PMID- 27203645 TI - Children in Australia's immigration centres. PMID- 27203646 TI - Risk of stent thrombosis with bioresorbable vascular scaffolds. PMID- 27203647 TI - IST-3 stroke trial data available. PMID- 27203648 TI - Risk of stent thrombosis with bioresorbable vascular scaffolds - Authors' reply. PMID- 27203649 TI - Intraoperative radiation therapy for breast cancer: a patient's view. PMID- 27203650 TI - Blood shortages and donation in China. PMID- 27203651 TI - Blood shortages and donation in China. PMID- 27203652 TI - Challenges of rare diseases in China. PMID- 27203653 TI - The Framework Convention on Tobacco Control. PMID- 27203654 TI - Sugary drinks tax: response from the Institute for Fiscal Studies. PMID- 27203656 TI - Department of Error. PMID- 27203655 TI - Organ and human trafficking in Nepal. PMID- 27203657 TI - Department of Error. PMID- 27203658 TI - Department of Error. PMID- 27203659 TI - Department of Error. PMID- 27203660 TI - Hepatitis C viraemia after apparent spontaneous clearance in a vertically infected child. PMID- 27203661 TI - Hepatitis C viraemia after apparent spontaneous clearance. PMID- 27203662 TI - EIT2015: promoting electrical impedance tomography as a non-invasive monitoring technology. PMID- 27203663 TI - Electrolysis of metal oxides in MgCl2 based molten salts with an inert graphite anode. AB - Electrolysis of solid metal oxides has been demonstrated in MgCl2-NaCl-KCl melt at 700 degrees C taking the electrolysis of Ta2O5 as an example. Both the cathodic and anodic processes have been investigated using cyclic voltammetry, and potentiostatic and constant voltage electrolysis, with the cathodic products analysed by XRD and SEM and the anodic products by GC. Fast electrolysis of Ta2O5 against a graphite anode has been realized at a cell voltage of 2 V, or a total overpotential of about 400 mV. The energy consumption was about 1 kW h kgTa(-1) with a nearly 100% Ta recovery. The cathodic product was nanometer Ta powder with sizes of about 50 nm. The main anodic product was Cl2 gas, together with about 1 mol% O2 gas and trace amounts of CO. The graphite anode was found to be an excellent inert anode. These results promise an environmentally-friendly and energy efficient method for metal extraction by electrolysis of metal oxides in MgCl2 based molten salts. PMID- 27203664 TI - Curcumin alleviates renal dysfunction and suppresses inflammation by shifting from M1 to M2 macrophage polarization in daunorubicin induced nephrotoxicity in rats. AB - The molecular mechanism of curcumin in macrophage polarization remains unknown in renal failure. We examined, whether curcumin treatment is associated with the modulation of renal function and macrophage phenotype switch in daunorubicin (DNR) induced nephrotoxicity model. Sprague-Dawley rats were treated with a cumulative dose of 9mg/kg DNR (i.v). Followed by curcumin (100mg/kg) administration orally every day for 6weeks. DNR treated rats showed nephrotoxicity as evidenced by worsening renal function, which was assessed by measuring creatinine and blood urea nitrogen in serum. These changes were reversed by treatment with curcumin, which resulted in significant improvement in renal function. Furthermore, curcumin increased cluster of differentiation (CD)163 expression, and down-regulated renal expression of antigen II type I receptor (AT1R), endothelin (ET)1, ET receptor type A and B (ETAR and ETBR), CD68 and CD80. Renal protein expression of extracellular signal-regulated kinase (ERK)1/2 and nuclear factor (NF)kappaB p65 were increased in DNR treated rats, and treatment with curcumin attenuated these increased expression. Curcumin mediated a further increase in the levels of interleukin (IL)-10. In addition, the expression of M1 phenotype was increased in DNR treated rats, which were attenuated by curcumin. Taken together, our results demonstrated that polyphenol curcumin has an ability to improve renal function and might induce the phenotypic switching from M1 to M2 macrophage polarization in DNR induced nephrotoxicity in rats. PMID- 27203665 TI - Soluble OX40L favors tumor rejection in CT26 colon carcinoma model. AB - OX40 receptor-expressing regulatory T cells (Tregs) populate tumors and suppress a variety of immune cells, posing a major obstacle for cancer immunotherapy. Different ways to functionally inactivate Tregs by triggering OX40 receptor have been suggested, including anti-OX40 antibodies and Fc:OX40L fusion proteins. To investigate whether the soluble extracellular domain of OX40L (OX40Lexo) is sufficient to enhance antitumor immune response, we generated an OX40Lexo expressing CT26 colon carcinoma cell line and studied its tumorigenicity in immunocompetent BALB/c and T cell deficient nu/nu mice. We found that soluble OX40L expressed in CT26 colon carcinoma favors the induction of an antitumor response which is not limited just to cells co-expressing EGFP as an antigenic determinant, but also eliminates CT26 cells expressing another fluorescent protein, KillerRed. Tumor rejection required the presence of T lymphocytes, as indicated by the unhampered tumor growth in nu/nu mice. Subsequent re-challenge of tumor-free BALB/c mice with CT26 EGFP cells resulted in no tumor growth, which is indicative of the formation of immunological memory. Adoptive transfer of splenocytes from mice that successfully rejected CT26 OX40Lexo EGFP tumors to naive mice conferred 100% resistance to subsequent challenge with the CT26 EGFP tumor. PMID- 27203666 TI - Geographies of medicalized welfare: Spatial analysis of supplemental security income in the U.S., 2000-2010. AB - In the post-1996 welfare reform period in the U.S., disability assistance has become a significant source of government aid for low-income residents as other forms of public support have faced considerable reductions and restrictions. In order to qualify for Supplemental Security Income (SSI) - a means-tested assistance program that provides income stipends to qualified residents - working age individuals with disabilities must have little income and resources, and procure medical documentation that confirms that they are unable to work due to a disability. The result of rising SSI enrollment in the face of cutbacks to other government programs is the increasing medicalization of welfare, whereby receipt of welfare benefits is contingent on a medical diagnosis of disability. Using county-level data from the American Community Survey and the Social Security Administration, this paper examines the changing spatial patterns of SSI participation of the working-age population in 2000 and 2010 across the U.S. in addition to the interconnections between disability, welfare, and poverty. Results from spatial analyses illustrate geographic variation in SSI prevalence, with distinctive spatial clusters of higher than average SSI participation in the southeast and Appalachian regions of the U.S. and in northern California. Multiple linear regression model results reveal that SSI participation is significantly correlated with disability, poverty, race, family type, and level of education in both 2000 and 2010. The findings suggest that spatial concentrations of disability, poverty, and underemployment persist in largely rural areas. The discussion explores the potential social and economic implications of long-term SSI clustering on localities and residents, and points to future research directions. PMID- 27203667 TI - Health, employment and relationships: Correlates of personal wellbeing in young adults with and without a history of childhood language impairment. AB - OBJECTIVE: We examine the potential associations between self-rated health, employment situation, relationship status and personal wellbeing in young adults with and without a history of language impairment (LI). METHODS: In total, 172 24 year-olds from the UK participated, with approximately half (N = 84) having a history of LI. Personal wellbeing was measured using ratings from three questions from the Office for National Statistics regarding life satisfaction, happiness and life being worthwhile. RESULTS: There were similarities between individuals with a history of LI and their age-matched peers in self-rated personal wellbeing. However, regression analyses revealed self-rated health was the most consistent predictor of personal wellbeing for individuals with a history of LI in relation to life satisfaction (21% of variance), happiness (11%) and perceptions that things one does in life are worthwhile (32%). None of the regression analyses were significant for their peers. CONCLUSIONS: Similarities on ratings of wellbeing by young adults with and without a history of LI can mask heterogeneity and important differences. Young adults with a history of LI are more vulnerable to the effects of health, employment and relationship status on their wellbeing than their peers. PMID- 27203668 TI - Erythematous nodes, urticarial rash and arthralgias in a large pedigree with NLRC4-related autoinflammatory disease, expansion of the phenotype. PMID- 27203669 TI - Dual role for Sox2 in specification of sensory competence and regulation of Atoh1 function. AB - The formation of inner ear sensory epithelia is believed to occur in two steps, initial specification of sensory competent (prosensory) regions followed by determination of specific cell-types, such as hair cells (HCs) and supporting cells. However, studies in which the HC determination factor Atoh1 was ectopically expressed in nonprosensory regions indicated that expression of Atoh1 alone is sufficient to induce HC formation suggesting that prosensory formation may not be a prerequisite for HC development. To test this hypothesis, interactions between Sox2 and Atoh1, which are required for prosensory and HC formation respectively, were examined. Forced expression of Atoh1 in nonprosensory cells resulted in transient expression of Sox2 prior to HC formation, suggesting that expression of Sox2 is required for formation of ectopic HCs. Moreover, Atoh1 overexpression failed to induce HC formation in Sox2 mutants, confirming that Sox2 is required for prosensory competence. To determine whether expression of Sox2 alone is sufficient to induce prosensory identity, Sox2 was transiently activated in a manner that mimicked endogenous expression. Following transient Sox2 activation, nonprosensory cells developed as HCs, a result that was never observed in response to persistent expression of Sox2. These results, suggest a dual role for Sox2 in inner ear formation. Initially, Sox2 is required to specify prosensory competence, but subsequent down-regulation of Sox2 must occur to allow Atoh1 expression, most likely through a direct interaction with the Atoh1 promoter. These results implicate Sox2-mediated changes in prosensory cells as an essential step in their ability to develop as HCs. (c) 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 3-13, 2017. PMID- 27203670 TI - Efficacy of CD46-targeting chimeric Ad5/35 adenoviral gene therapy for colorectal cancers. AB - CD46 is a complement inhibitor membrane cofactor which also acts as a receptor for various microbes, including species B adenoviruses (Ads). While most Ad gene therapy vectors are derived from species C and infect cells through coxsackie adenovirus receptor (CAR), CAR expression is downregulated in many cancer cells, resulting inefficient Ad-based therapeutics. Despite a limited knowledge on the expression status of many cancer cells, an increasing number of cancer gene therapy studies include fiber-modified Ad vectors redirected to the more ubiquitously expressed CD46. Since our finding from tumor microarray indicate that CD46 was overexpressed in cancers of the prostate and colon, fiber chimeric Ad5/35 vectors that have infection tropism for CD46 were employed to demonstrate its efficacy in colorectal cancers (CRC). CD46-overexpressed cells showed a significantly higher response to Ad5/35-GFP and to Ad5/35-tk/GCV. While CRC cells express variable levels of CD46, CD46 expression was positively correlated with Ad5/35-mediated GFP fluorescence and accordingly its cell killing. Injection of Ad5/35-tk/GCV caused much greater tumor-suppression in mice bearing CD46 overexpressed cancer xenograft compared to mock group. Analysis of CRC samples revealed that patients with positive CD46 expression had a higher survival rate (p=0.031), carried tumors that were well-differentiated, but less invasive and metastatic, and with a low T stage (all p<0.05). Taken together, our study demonstrated that species B-based adenoviral gene therapy is a suitable approach for generally CD46-overexpressed CRC but would require careful consideration preceding CD46 analysis and categorizing CRC patients. PMID- 27203671 TI - Accumulation of RNA-dependent protein kinase (PKR) in the nuclei of lung cancer cells mediates radiation resistance. AB - We have previously demonstrated that radiation induced cell death in PKR (-/-) deficient mouse embryo fibroblasts (MEFs) but not in PKR (+/+) wild type MEFs. Our study indicated that PKR can also be involved in survival pathways following radiation therapy through activation of the AKT survival pathways in these MEFs is mediated in part through PKR. The role of PKR on radiation sensitivity in cancer cells has not been evaluated. In this study, we demonstrated that radiation treatment causes nuclear translocation of PKR in human lung cancer cells. The transduction of lung cancer cells with a dominant negative adenoviral PKR vector blocks nuclear translocation of PKR and leads to the reversal of radiation resistance. Plasmid transduction of lung cancer cells with nuclear targeted wild type PKR vectors also increased radiation resistance. This effect is selectively abrogated by plasmid transduction of dominant negative PKR vectors which restore radiation sensitivity. These findings suggest a novel role for PKR in lung cancer cells as a mediator of radiation resistance possibly through translocation of the protein product to the nucleus. PMID- 27203672 TI - Drug conjugated nanoparticles activated by cancer cell specific mRNA. AB - We describe a customizable approach to cancer therapy in which a gold nanoparticle (Au-NP) delivers a drug that is selectively activated within the cancer cell by the presence of an mRNA unique to the cancer cell. Fundamental to this approach is the observation that the amount of drug released from the Au-NP is proportional to both the presence and abundance of the cancer cell specific mRNA in a cell. As proof-of-principle, we demonstrate both the efficient delivery and selective release of the multi-kinase inhibitor dasatinib from Au-NPs in leukemia cells with resulting efficacy in vitro and in vivo. Furthermore, these Au-NPs reduce toxicity against hematopoietic stem cells and T-cells. This approach has the potential to improve the therapeutic efficacy of a drug and minimize toxicity while being highly customizable with respect to both the cancer cell specific mRNAs targeted and drugs activated. PMID- 27203673 TI - Effect of nodal status on clinical outcomes of triple-negative breast cancer: a population-based study using the SEER 18 database. AB - Triple-negative breast cancer (TNBC) is an aggressive malignancy with a poor prognosis. Data from the Surveillance, Epidemiology and End Results database (2010-2012) were used to identify 10,771 patients with TNBC, and we assessed the effects of lymph node (LN) status on breast cancer-specific survival (BCSS) and overall survival (OS). In our study, a Kaplan-Meier plot showed that LN-negative patients (N0) had better survival outcomes than LN-positive patients and that patients with >=10 positive LNs (N3) exhibited the worst survival outcomes regardless of tumor size. A pairwise comparison showed no difference in survival outcomes among each group stratified by tumor size. Further, for LN-positive patients with a tumor size <=2 cm (T1) or >5 cm (T3), there were similar outcomes between patients with one to three LNs (N1) and those with four to nine LNs (N2), whereas N1 patients experienced significantly better survival outcomes than N3 patients (P<0.001). Therefore, ten metastatic lymph nodes was the cut-off value for poor prognosis. Nevertheless, for patients with a tumor size of 2-5 cm (T2), the extent of LN involvement contributed prognostic value to OS but not BCSS. In summary, we found that nodal status and tumor size exhibited distinct interaction patterns for predicting the outcomes of TNBC. These results provide deeper insight into the prognostic value of nodal status in TNBC. PMID- 27203674 TI - RNF216 contributes to proliferation and migration of colorectal cancer via suppressing BECN1-dependent autophagy. AB - Originally identified as an E3 ligase regulating toll-like receptor (TLR) signaling, ring finger protein 216 (RNF216) also plays an essential role in autophagy, which is fundamental to cellular homeostasis. Autophagy dysfunction leads to an array of pathological events, including tumor formation. In this study, we found that RNF216 was upregulated in human colorectal cancer (CRC) tissues and cell lines, and was associated with progression of CRC. RNF216 promoted CRC cell proliferation and migration in vitro and in vivo, largely by enhancing proteasomal degradation of BECN1, a key autophagy regulator and tumor suppressor. RNF216 restricted CRC cell autophagy through BECN1 inhibition under nutritional starvation conditions. RNF216 knockdown increased the autophagy, limiting CRC cell proliferation and migration. Moreover, BECN1 knockdown or autophagy inhibition restored proliferation and migration of RNF216-knockdown CRC cells. Collectively, our results suggested that RNF216 promoted CRC cell proliferation and migration by negatively regulating BECN1-dependent autophagy. This makes RNF216 as a potential biomarker and novel therapeutic target for inhibiting CRC development and progression. PMID- 27203675 TI - Co-option of pre-existing vascular beds in adipose tissue controls tumor growth rates and angiogenesis. AB - Many types of cancer develop in close association with highly vascularized adipose tissues. However, the role of adipose pre-existing vascular beds on tumor growth and angiogenesis is unknown. Here we report that pre-existing microvascular density in tissues where tumors originate is a crucial determinant for tumor growth and neovascularization. In three independent tumor types including breast cancer, melanoma, and fibrosarcoma, inoculation of tumor cells in the subcutaneous tissue, white adipose tissue (WAT), and brown adipose tissue (BAT) resulted in markedly differential tumor growth rates and angiogenesis, which were in concordance with the degree of pre-existing vascularization in these tissues. Relative to subcutaneous tumors, WAT and BAT tumors grew at accelerated rates along with improved neovascularization, blood perfusion, and decreased hypoxia. Tumor cells implanted in adipose tissues contained leaky microvessel with poor perivascular cell coverage. Thus, adipose vasculature predetermines the tumor microenvironment that eventually supports tumor growth. PMID- 27203676 TI - Significant change of cytochrome P450s activities in patients with hepatocellular carcinoma. AB - The lack of information concerning individual variation in drug-metabolizing enzymes is one of the most important obstacles for designing personalized medicine approaches for hepatocellular carcinoma (HCC) patients. To assess cytochrome P450 (CYP) in the metabolism of endogenous and exogenous molecules in an HCC setting, the activity changes of 10 major CYPs in microsomes from 105 normal and 102 HCC liver tissue samples were investigated. We found that CYP activity values expressed as intrinsic clearance (CLint) differed between HCC patients and control subjects. HCC patient samples showed increased CLint for CYP2C9, CYP2D6, and CYP2E1 compared to controls. Meanwhile, CYP1A2, CYP2C8, and CYP2C19 CLint values decreased and CYP2A6, CYP2B6, and CYP3A4/5 activity was unchanged relative to controls. For patients with HCC accompanied by fibrosis or cirrhosis, the same activity changes were seen for the CYP isoforms, except for CYP2D6 which had higher values in HCC patients with cirrhosis. Moreover, CYP2D6*10 (100C>T), CYP2C9*3 (42614 A>C), and CYP3A5*3 (6986A>G) polymorphisms had definite effects on enzyme activities. In the HCC group, the CLint of CYP2D6*10 mutant homozygote was decreased by 95% compared to wild-type samples, and the frequency of this homozygote was 2.8-fold lower than the controls.In conclusion, the activities of CYP isoforms were differentially affected in HCC patients. Genetic polymorphisms of some CYP enzymes, especially CYP2D6*10, could affect enzyme activity. CYP2D6*10 allelic frequency was significantly different between HCC patients and control subjects. These findings may be useful for personalizing the clinical treatment of HCC patients as well as predicting the risk of hepatocarcinogenesis. PMID- 27203680 TI - Efficacy of different caffeine concentrations on growth and ochratoxin A production by Aspergillus species. AB - The objective of this study was to evaluate the effect of different caffeine concentrations (0-4%) on (i) lag phase prior to growth, (ii) growth rates and (iii) ochratoxin A (OTA) production by strains from the Aspergillus section Circumdati and Aspergillus section Nigri groups, isolated from coffee, when grown on a conducive medium at 0.98 water activity and 30 degrees C. The lag phases prior to growth increased with caffeine concentration. A strain of Aspergillus niger and Aspergillus carbonarius were the most sensitive to caffeine with growth being inhibited by <1% caffeine. For strains of Aspergillus westerdijkiae, Aspergillus ochraceus and Aspergillus steynii, although growth was inhibited significantly, some growth (10-15% of controls) occurred in 4% caffeine. OTA production was significantly inhibited by only 0.5% caffeine for strains of A. westerdijkiae, A. niger and A. carbonarius. For A. steynii at least 1.5% caffeine was required to inhibit OTA production. In contrast, for the strain of A. ochraceus there was a stimulation of OTA at 3% with a reduction at 4% caffeine. These results are discussed in the context of the different concentrations of caffeine found in Arabica and Robusta coffee and the development of minimization strategies. SIGNIFICANCE AND IMPACT OF THE STUDY: Arabic (0.6%) and Robusta coffee (4%) have significantly different amounts of endogenous caffeine. The growth of six ochratoxigenic fungi which contaminate coffee with ochratoxin A (OTA) had differential tolerance/sensitivity to concentrations of caffeine in vitro in this range. However, low concentrations of caffeine (<0.5%) was inhibitory to OTA production. These results are discussed in the context of the potential for using such information for the design of minimization strategies to control mycotoxin production in such products. PMID- 27203677 TI - Sorafenib inhibits macrophage-mediated epithelial-mesenchymal transition in hepatocellular carcinoma. AB - Tumor-associated macrophages, crucial components of the microenvironment in hepatocellular carcinoma, hamper anti-cancer immune responses. The aim of the present study was to investigate the effect of sorafenib on the formation of the tumor microenvironment, especially the relationship between polarized macrophages and hepatocytes. Macrophage infiltration was reduced in patients with hepatocellular carcinoma who were treated with sorafenib. In vitro, sorafenib abolished polarized macrophage-induced epithelial mesenchymal transition (EMT) and migration of hepatocellular carcinoma cells but not normal hepatocytes. Moreover, sorafenib attenuated HGF secretion in polarized macrophages, and decreased plasma HGF in patients with hepatocellular carcinoma. Additionally, sorafenib abolished the polarized macrophage-induced activation of the HGF receptor Met in hepatocellular carcinoma cells. Our findings suggest that sorafenib inhibits polarized macrophage-induced EMT in hepatocellular carcinoma cells via the HGF-Met signaling pathway. These results contribute to our understanding of the immunological mechanisms that underlie the protective effects of sorafenib in hepatocellular carcinoma therapy. PMID- 27203678 TI - Cabazitaxel operates anti-metastatic and cytotoxic via apoptosis induction and stalls brain tumor angiogenesis. AB - Taxanes target microtubules and are clinically established chemotherapeutic agents with proven efficacy in human cancers. Cabazitaxel (XRP-6258, Jevtana(r)) is a second generation semisynthetic taxane with high chemotherapeutic potential in prostate cancer. There, cabazitaxel can overcome docetaxel-resistant prostate cancer. Here, we tested the effects of cabazitaxel on glioma cells, and non transformed cells such as neurons and astrocytes. Cabazitaxel operates highly toxic in various human glioma cells at nanomolar concentrations. In contrast, primary astrocytes and neurons are not affected by this agent. Cabazitaxel disrupts cytoskeletal F-actin fibers and induces apoptotic cell death in gliomas. Moreover, cabazitaxel displayed highest efficacy in inhibiting glioma cell migration and invasion. Here we demonstrate that cabazitaxel inhibited tumor migration already at 1 nM. We also tested cabazitaxel in the ex vivo VOGiM assay. Cabazitaxel stalled glioma growth and at the same time inhibited tumor-induced angiogenesis. In summary, we found that cabazitaxel operates as an apoptosis inducing gliomatoxic agent with strongest effects on migration and invasive growth. Thus, our report uncovered cabazitaxel actions on gliomas and on the brain tumor microenvironment. These data reveal novel aspects for adjuvant approaches when applied to brain tumor patients. PMID- 27203679 TI - The potential role of epigenetic modulations in BPPV maneuver exercises. AB - Benign paroxysmal positional vertigo (BPPV) is one of the most common complaints encountered in clinics and is strongly correlated with advanced age or, possibly, degeneration. Redistribution exercises are the most effective approaches to treat BPPV, and canalith repositioning procedure (CRP) cure most BPPV cases. However, the mechanisms through which the treatment modulates systemic molecules in BPPV patients remain largely unknown. In this study, we report that the miR-34a and Sirtuin 1 (SIRT1) genes correlated with the treatment effects of CRP in BPPV subjects. We found that miR-34a expression was largely inhibited and SIRT1 expression was significantly reversed after BPPV maneuver treatment. We also confirmed that the PPAR-gamma, PGC-1 and FoxO gene expressions were decreased immediately after canalith repositioning procedure (CRP) for BPPV, and were largely increased after a complete cure of BPPV. Moreover, we observed that after a complete recovery of BPPV, the ROS concentrations, pro-inflammatory cytokine concentrations and p53 expression levels were attenuated. We conclude that BPPV treatment might involve some epigenetic regulations through the mediation of miR 34a, SIRT1 functions and repression of redox status. PMID- 27203682 TI - Outcomes of Minimal Invasive vs Open Radical Nephrectomy for the Treatment of Locally Advanced Renal-Cell Carcinoma. AB - PURPOSE: We compare oncologic outcomes of minimally invasive and open nephrectomy for locally advanced kidney cancer. MATERIALS AND METHODS: A retrospective review of a single-institutional, prospectively maintained database from a National Comprehensive Cancer Network-designated center was conducted. All patients who underwent radical nephrectomy at Roswell Park Cancer Institute with diagnosis of pT3 and pT4 renal-cell carcinoma (RCC) between years 1998 and 2015 were reviewed. Patients who underwent partial nephrectomy and nephroureterectomy were excluded. RESULTS: We identified 172 patients with pT3 or pT4 tumors resected by minimally invasive (laparoscopic and robotic) or open radical nephrectomy. Demographic characteristics were similar between the two groups. Patients in the minimally invasive group had a higher mean body mass index (31.9 vs 28.1, p = 0.002), radiologically smaller tumors (7.7 cm vs 9.1 cm, p = 0.008), lower mean estimated blood loss (277 vs 1429, p < 0.001), lower rate of blood transfusion (4.7% vs 45.5%, p < 0.001), and a shorter mean length of stay (3.5 days vs 5.7 days, p < 0.001) compared with patients who underwent open surgery. At a median follow-up of 32.8 months, there was no significant difference in overall survival (p = 0.8) between the two groups. CONCLUSION: Minimal invasive nephrectomy is a safe approach with similar oncologic outcomes to open nephrectomy for select patients with locally advanced RCC. PMID- 27203681 TI - Classifying eating disorders based on "healthy" and "unhealthy" perfectionism and impulsivity. AB - OBJECTIVE: Perfectionism and impulsivity are associated with eating disorders (EDs). The current study examines whether clinically relevant subgroups of women with EDs can be identified based on "healthy" and "unhealthy" perfectionism and impulsivity. METHOD: Latent profile analyses (LPA) were performed on data of 844 patients (DSM-IV diagnosis: 381 anorexia nervosa, 146 bulimia nervosa, 56 binge eating disorder, 261 ED not otherwise specified). "Healthy" and "unhealthy" forms of perfectionism and impulsivity were assessed by the Frost Multidimensional Perfectionism Scale and the Dickman Impulsivity Inventory, respectively. The Eating Disorder Examination Questionnaire was completed to assess ED psychopathology. Furthermore, in 229 patients additional ED symptoms, depression, self-esteem, obsessive-compulsive symptoms, and personality features were assessed. RESULTS: The LPA revealed four profiles; 1. "Healthy Impulsivity" (HI; n = 191), 2. "Unhealthy Impulsivity" (UI; n = 238), 3. "Healthy and Unhealthy Perfectionism" (HP + UP; n = 153), 4. "Healthy Perfectionism" (HP; n = 262). Patients belonging to the "HP + UP" and the "UI" classes reported higher levels of ED psychopathology. More severe comorbid symptoms (depressive, obsessive compulsive and self-esteem) were found in the patients belonging to the "HP + UP" class. Patients from the "HP + UP" and "HP" classes had higher scores for the personality features Harm Avoidance, Persistence and Cooperativeness. DISCUSSION: Women with EDs could be meaningfully grouped according to perfectionism and impulsivity. These findings can be used to improve treatment matching and intervention strategies. The use of dimensional features, like perfectionism and impulsivity, in ED research, may enable the identification of fundamental underlying mechanisms and provide more insight into potential mechanisms that may drive or maintain disordered eating. (c) 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:673-680). PMID- 27203683 TI - A non-topological mechanism for negative linear compressibility. AB - Negative linear compressibility (NLC), the increase in a unit cell length with pressure, is a rare phenomenon in which hydrostatic compression of a structure promotes expansion along one dimension. It is usually a consequence of crystal structure topology. We show that the source of NLC in the Co(ii) citrate metal organic framework UTSA-16 lies not in framework topology, but in the relative torsional flexibility of Co(ii)-centred tetrahedra compared to more rigid octahedra. PMID- 27203686 TI - Dipolar Photosystems: Engineering Oriented Push-Pull Components into Double- and Triple-Channel Surface Architectures. AB - Push-pull aromatics are not popular as optoelectronic materials because their supramolecular organization is difficult to control. However, recent progress with synthetic methods has suggested that the directional integration of push pull components into multicomponent photosystems should become possible. In this study, we report the design, synthesis, and evaluation of double- or triple channel architectures that contain pi stacks with push-pull components in parallel or mixed orientation. Moreover, the parallel push-pull stacks were uniformly oriented with regard to co-axial stacks, either with inward or outward oriented push-pull dipoles. Hole-transporting (p) aminoperylenemonoimides (APIs) and aminonaphthalimides (ANIs) are explored for ordered push-pull stacks. For the co-axial electron-transporting (n) stacks, naphthalenediimides (NDIs) are used. In double-channel photosystems, mixed push-pull stacks are overall less active than parallel push-pull stacks. The orientation of the parallel push-pull stacks with regard to the co-axial NDI stacks has little influence on activity. In triple-channel photosystems, outward-directed dipoles in bridging stacks between peripheral p and central n channels show higher activity than inward-directed dipolar stacks. Higher activities in response to direct irradiation of outward directed parallel stacks reveal the occurrence of quite remarkable optical gating. PMID- 27203684 TI - Mitofusin-2 knockdown increases ER-mitochondria contact and decreases amyloid beta-peptide production. AB - Mitochondria are physically and biochemically in contact with other organelles including the endoplasmic reticulum (ER). Such contacts are formed between mitochondria-associated ER membranes (MAM), specialized subregions of ER, and the outer mitochondrial membrane (OMM). We have previously shown increased expression of MAM-associated proteins and enhanced ER to mitochondria Ca(2+) transfer from ER to mitochondria in Alzheimer's disease (AD) and amyloid beta-peptide (Abeta) related neuronal models. Here, we report that siRNA knockdown of mitofusin-2 (Mfn2), a protein that is involved in the tethering of ER and mitochondria, leads to increased contact between the two organelles. Cells depleted in Mfn2 showed increased Ca(2+) transfer from ER to mitchondria and longer stretches of ER forming contacts with OMM. Interestingly, increased contact resulted in decreased concentrations of intra- and extracellular Abeta40 and Abeta42 . Analysis of gamma-secretase protein expression, maturation and activity revealed that the low Abeta concentrations were a result of impaired gamma-secretase complex function. Amyloid-beta precursor protein (APP), beta-site APP-cleaving enzyme 1 and neprilysin expression as well as neprilysin activity were not affected by Mfn2 siRNA treatment. In summary, our data shows that modulation of ER-mitochondria contact affects gamma-secretase activity and Abeta generation. Increased ER mitochondria contact results in lower gamma-secretase activity suggesting a new mechanism by which Abeta generation can be controlled. PMID- 27203685 TI - Reactome from a WikiPathways Perspective. AB - Reactome and WikiPathways are two of the most popular freely available databases for biological pathways. Reactome pathways are centrally curated with periodic input from selected domain experts. WikiPathways is a community-based platform where pathways are created and continually curated by any interested party. The nascent collaboration between WikiPathways and Reactome illustrates the mutual benefits of combining these two approaches. We created a format converter that converts Reactome pathways to the GPML format used in WikiPathways. In addition, we developed the ComplexViz plugin for PathVisio which simplifies looking up complex components. The plugin can also score the complexes on a pathway based on a user defined criterion. This score can then be visualized on the complex nodes using the visualization options provided by the plugin. Using the merged collection of curated and converted Reactome pathways, we demonstrate improved pathway coverage of relevant biological processes for the analysis of a previously described polycystic ovary syndrome gene expression dataset. Additionally, this conversion allows researchers to visualize their data on Reactome pathways using PathVisio's advanced data visualization functionalities. WikiPathways benefits from the dedicated focus and attention provided to the content converted from Reactome and the wealth of semantic information about interactions. Reactome in turn benefits from the continuous community curation available on WikiPathways. The research community at large benefits from the availability of a larger set of pathways for analysis in PathVisio and Cytoscape. The pathway statistics results obtained from PathVisio are significantly better when using a larger set of candidate pathways for analysis. The conversion serves as a general model for integration of multiple pathway resources developed using different approaches. PMID- 27203687 TI - Neighbour Origin and Ploidy Level Drive Impact of an Alien Invasive Plant Species in a Competitive Environment. AB - Our understanding of the potential mechanisms driving the spread and naturalization of alien plant species has increased over the past decades, but specific knowledge on the factors contributing to their increased impact in the introduced range is still urgently needed. The native European plant Centaurea stoebe occurs as two cytotypes with different life histories (monocarpic diploids, allo-polycarpic tetraploids). However, only tetraploids have been found in its introduced range in North America, where C. stoebe has become a most prominent plant invader. Here, we focus on the ploidy level of C. stoebe and origin of neighbouring community in explaining the high impact during the invasion of new sites in the introduced range. We conducted a mesocosm experiment under open-field conditions with the diploid (EU2x) and tetraploid (EU4x) cytotype of Centaurea stoebe from its native European (EU) range, and with the invasive tetraploid (NA4x) cytotype from the introduced North American (NA) range in competition with EU (old) or NA (new) neighbouring plant communities. In the presence of competition, the biomass of EU neighbouring community was reduced to a comparable level by all three geo-cytotypes of C. stoebe. In contrast, the biomass of the NA neighbouring community was reduced beyond when competing with tetraploid, but not with diploid C. stoebe. The fact that the biomass of all three geo-cytotypes of C. stoebe was correlated with the biomass of the EU neighbouring community, but not with that of the NA neighbouring community suggests that different mechanisms underlie the competitive interactions between C. stoebe and its old vs. new neighbouring communities, such as competition for the same limiting resources at home vs competition through novel allelo-chemicals or differential resource uptake strategies in the introduced range. We therefore caution to simply use the ecosystem impact assessed at home to predict impact in the introduced range. PMID- 27203688 TI - Dual-targeting hybrid nanoparticles for the delivery of SN38 to Her2 and CD44 overexpressed human gastric cancer. AB - Gastric cancer (GC), particularly of the type with high expression of both human epidermal growth factor receptor 2 (Her2) and cluster determinant 44 (CD44), is one of the most malignant human tumors which causes a high mortality rate due to rapid tumor growth and metastasis. To develop effective therapeutic treatments, a dual-targeting hybrid nanoparticle (NP) system was designed and constructed to deliver the SN38 agent specifically to human solid gastric tumors bearing excessive Her2 and CD44. The hybrid NPs consist of a particle core made of the biodegradable polymer PLGA and a lipoid shell prepared by conjugating the AHNP peptides and n-hexadecylamine (HDA) to the carboxyl groups of hyaluronic acid (HA). Upon encapsulation of the SN38 agent in the NPs, the AHNP peptides and HA on the NP surface allow preferential delivery of the drug to gastric cancer cells (e.g., HGC27 cells) by targeting Her2 and CD44. Cellular uptake and in vivo biodistribution experiments verified the active targeting and prolonged in vivo circulation properties of the dual-targeting hybrid NPs, leading to enhanced accumulation of the drug in tumors. Furthermore, the anti-proliferation mechanism studies revealed that the inhibition of the growth and invasive activity of HGC27 cells was not only attributed to the enhanced cellular uptake of dual-targeting NPs, but also benefited from the suppression of CD44 and Her2 expression by HA and AHNP moieties. Finally, intravenous administration of the SN38-loaded dual targeting hybrid NPs induced significant growth inhibition of HGC27 tumor xenografted in nude mice compared with a clinical antitumor agent, Irinotecan (CPT-11), and the other NP formulations. These results demonstrate that the designed dual-targeting hybrid NPs are promising for targeted anti-cancer drug delivery to treat human gastric tumors over-expressing Her2 and CD44. PMID- 27203690 TI - Competitive Assays of Label-Free DNA Hybridization with Single-Molecule Fluorescence Imaging Detection. AB - Single-molecule imaging of fluorescently labeled biomolecules is a powerful technique for measuring association interactions; however, care must be taken to ensure that the fluorescent labels do not influence the system being probed. Label-free techniques are needed to understand biomolecule interactions free from the influence of an attached label, but these techniques often lack sensitivity and specificity. To solve these challenges, we have developed a competitive assay that uses single-molecule detection to track the population of unlabeled target single-stranded DNA (ssDNA) hybridized with probe DNA immobilized at a glass interface by detecting individual duplexes with a fluorescently labeled "tracer" ssDNA. By labeling a small fraction (<0.2%) of target molecules, the "tracer" DNA tracks the available probe DNA sites without significant competition with the unlabeled target population. Single-molecule fluorescence imaging is a good read out scheme for competitive assays, as it is sufficiently sensitive to detect tracer DNA on substrates with relatively low densities of probe DNA, ~10(-3) of a monolayer, so that steric interactions do not hinder DNA hybridization. Competitive assays are used to measure the association constant of complementary strand DNA hybridization of 9- and 10-base pair targets, where the tracer assay predicts the same association constant as a traditional displacement competitive assay. This methodology was used to compare the Ka of hybridization for identical DNA strands differing only by the presence of a fluorescent label tethered to the 5' end of the solution-phase target. The addition of the fluorescent label significantly stabilizes the DNA duplex by 3.6 kJmol(-1), adding more stability than an additional adenine-thymine base-pairing interaction, 2.7 kJmol(-1). This competitive tracer assay could be used to screen a number of labeled and unlabeled target DNA strands to measure the impact of fluorescent labeling on duplex stability. This single-molecule competitive hybridization scheme could be easily adapted into a sensitive assay, where competition between tracer and target oligonucleotides for probe sites could be used to measure concentrations of unlabeled DNA or RNA. PMID- 27203689 TI - Exposure to Aedes aegypti Bites Induces a Mixed-Type Allergic Response following Salivary Antigens Challenge in Mice. AB - Classical studies have shown that Aedes aegypti salivary secretion is responsible for the sensitization to mosquito bites and many of the components present in saliva are immunogenic and capable of inducing an intense immune response. Therefore, we have characterized a murine model of adjuvant-free systemic allergy induced by natural exposure to mosquito bites. BALB/c mice were sensitized by exposure to A. aegypti mosquito bites and intranasally challenged with phosphate buffered saline only or the mosquito's salivary gland extract (SGE). Blood, bronchoalveolar lavage (BAL) and lung were collected and evaluated for cellularity, histopathological analyses, cytokines and antibody determination. Respiratory pattern was analyzed by Penh measurements and tracheal segments were obtained to study in vitro reactivity to methacholine. BAL recovered from sensitized mice following challenge with SGE showed an increased number of eosinophils and Th2 cytokines such as IL-4, IL-5 and IL-13. Peribronchoalveolar eosinophil infiltration, mucus and collagen were also observed in lung parenchyma of sensitized mice, suggesting the development of a typical Th2 response. However, the antibody profile in serum of these mice evidenced a mixed-type response with presence of both, IgG1/IgE (Th2-related) and IgG2a (Th1-related) isotypes. In addition, changes in breathing pattern and tracheal reactivity to methacholine were not found. Taken together, our results show that A. aegypti bites trigger an atypical allergic reaction, with some classical cellular and soluble Th2 components in the lung, but also systemic Th1 and Th2 antibody isotypes and no change in either the respiratory pattern or the trachea responsiveness to agonist. PMID- 27203691 TI - Correction: RUNX1B Expression Is Highly Heterogeneous and Distinguishes Megakaryocytic and Erythroid Lineage Fate in Adult Mouse Hematopoiesis. AB - [This corrects the article DOI: 10.1371/journal.pgen.1005814.]. PMID- 27203692 TI - Androgen-Sensitized Apoptosis of HPr-1AR Human Prostate Epithelial Cells. AB - Androgen receptor (AR) signaling is crucial to the development and homeostasis of the prostate gland, and its dysregulation mediates common prostate pathologies. The mechanisms whereby AR regulates growth suppression and differentiation of luminal epithelial cells in the prostate gland and proliferation of malignant versions of these cells have been investigated in human and rodent adult prostate. However, the cellular stress response of human prostate epithelial cells is not well understood, though it is central to prostate health and pathology. Here, we report that androgen sensitizes HPr-1AR and RWPE-AR human prostate epithelial cells to cell stress agents and apoptotic cell death. Although 5alpha-dihydrotestosterone (DHT) treatment alone did not induce cell death, co-treatment of HPr-1AR cells with DHT and an apoptosis inducer, such as staurosporine (STS), TNFt, or hydrogen peroxide, synergistically increased cell death in comparison to treatment with each apoptosis inducer by itself. We found that the synergy between DHT and apoptosis inducer led to activation of the intrinsic/mitochondrial apoptotic pathway, which is supported by robust cleavage activation of caspase-9 and caspase-3. Further, the dramatic depolarization of the mitochondrial membrane potential that we observed upon co-treatment with DHT and STS is consistent with increased mitochondrial outer membrane permeabilization (MOMP) in the pro-apoptotic mechanism. Interestingly, the synergy between DHT and apoptosis inducer was abolished by AR antagonists and inhibitors of transcription and protein synthesis, suggesting that AR mediates pro-apoptotic synergy through transcriptional regulation of MOMP genes. Expression analysis revealed that pro-apoptotic genes (BCL2L11/BIM and AIFM2) were DHT-induced, whereas pro-survival genes (BCL2L1/BCL-XL and MCL1) were DHT repressed. Hence, we propose that the net effect of these AR-mediated expression changes shifts the balance of BCL2-family proteins, such that androgen signaling sensitizes mitochondria to apoptotic signaling, thus rendering HPr-1AR more vulnerable to cell death signals. Our study offers insight into AR-mediated regulation of prostate epithelial cell death signaling. PMID- 27203694 TI - Frequency of Missed Insulin Boluses in Type 1 Diabetes and Its Impact on Diabetes Control. PMID- 27203693 TI - Molecular Ecological Insights into Neotropical Bird-Tick Interactions. AB - In the tropics, ticks parasitize many classes of vertebrate hosts. However, because many tropical tick species are only identifiable in the adult stage, and these adults usually parasitize mammals, most attention on the ecology of tick host interactions has focused on mammalian hosts. In contrast, immature Neotropical ticks are often found on wild birds, yet difficulties in identifying immatures hinder studies of birds' role in tropical tick ecology and tick-borne disease transmission. In Panama, we found immature ticks on 227 out of 3,498 individually-sampled birds representing 93 host species (24% of the bird species sampled, and 13% of the Panamanian land bird fauna). Tick parasitism rates did not vary with rainfall or temperature, but did vary significantly with several host ecological traits. Likewise, Neotropical-Nearctic migratory birds were significantly less likely to be infested than resident species. Using a molecular library developed from morphologically-identified adult ticks specifically for this study, we identified eleven tick species parasitizing birds, indicating that a substantial portion of the Panamanian avian species pool is parasitized by a diversity of tick species. Tick species that most commonly parasitized birds had the widest diversity of avian hosts, suggesting that immature tick species are opportunistic bird parasites. Although certain avian ecological traits are positively associated with parasitism, we found no evidence that individual tick species show specificity to particular avian host ecological traits. Finally, our data suggest that the four principal vectors of Rocky Mountain Spotted Fever in the Neotropics rarely, if ever, parasitize Panamanian birds. However, other tick species that harbor newly-discovered rickettsial parasites of unknown pathogenicity are frequently found on these birds. Given our discovery of broad interaction between Panamanian tick and avian biodiversity, future work on tick ecology and the dynamics of emerging tropical tick-borne pathogens should explicitly consider wild bird as hosts. PMID- 27203695 TI - Intra-Arterially Delivered Mesenchymal Stem Cells Are Not Detected in the Brain Parenchyma in an Alzheimer's Disease Mouse Model. AB - Mesenchymal stem cells (MSCs) have a promising role as a therapeutic agent for neurodegenerative diseases such as Alzheimer's disease (AD). Prior studies suggested that intra-arterially administered MSCs are engrafted into the brain in stroke or traumatic brain injury (TBI) animal models. However, a controversial standpoint exists in terms of the integrity of the blood brain barrier (BBB) in transgenic AD mice. The primary goal of this study was to explore the feasibility of delivering human umbilical cord-blood derived mesenchymal stem cells (hUCB MSCs) into the brains of non-transgenic WT (C3H/C57) and transgenic AD (APP/PS1) mice through the intra-arterial (IA) route. Through two experiments, mice were infused with hUCB-MSCs via the right internal carotid artery and were sacrificed at two different time points: 6 hours (experiment 1) or 5 minutes (experiment 2) after infusion. In both experiments, no cells were detected in the brain parenchyma while MSCs were detected in the cerebrovasculature in experiment 2. The results from this study highlight that intra-arterial delivery of MSCs is not the most favorable route to be implemented as a potential therapeutic approach for AD. PMID- 27203697 TI - Digital Mapping of Soil Salinity and Crop Yield across a Coastal Agricultural Landscape Using Repeated Electromagnetic Induction (EMI) Surveys. AB - Reliable and real-time information on soil and crop properties is important for the development of management practices in accordance with the requirements of a specific soil and crop within individual field units. This is particularly the case in salt-affected agricultural landscape where managing the spatial variability of soil salinity is essential to minimize salinization and maximize crop output. The primary objectives were to use linear mixed-effects model for soil salinity and crop yield calibration with horizontal and vertical electromagnetic induction (EMI) measurements as ancillary data, to characterize the spatial distribution of soil salinity and crop yield and to verify the accuracy of spatial estimation. Horizontal and vertical EMI (type EM38) measurements at 252 locations were made during each survey, and root zone soil samples and crop samples at 64 sampling sites were collected. This work was periodically conducted on eight dates from June 2012 to May 2013 in a coastal salt-affected mud farmland. Multiple linear regression (MLR) and restricted maximum likelihood (REML) were applied to calibrate root zone soil salinity (ECe) and crop annual output (CAO) using ancillary data, and spatial distribution of soil ECe and CAO was generated using digital soil mapping (DSM) and the precision of spatial estimation was examined using the collected meteorological and groundwater data. Results indicated that a reduced model with EMh as a predictor was satisfactory for root zone ECe calibration, whereas a full model with both EMh and EMv as predictors met the requirement of CAO calibration. The obtained distribution maps of ECe showed consistency with those of EMI measurements at the corresponding time, and the spatial distribution of CAO generated from ancillary data showed agreement with that derived from raw crop data. Statistics of jackknifing procedure confirmed that the spatial estimation of ECe and CAO exhibited reliability and high accuracy. A general increasing trend of ECe was observed and moderately saline and very saline soils were predominant during the survey period. The temporal dynamics of root zone ECe coincided with those of daily rainfall, water table and groundwater data. Long-range EMI surveys and data collection are needed to capture the spatial and temporal variability of soil and crop parameters. Such results allowed us to conclude that, cost-effective and efficient EMI surveys, as one part of multi-source data for DSM, could be successfully used to characterize the spatial variability of soil salinity, to monitor the spatial and temporal dynamics of soil salinity, and to spatially estimate potential crop yield. PMID- 27203696 TI - Time-Dependent Discrepancies between Assessments of Sensory Function after Incomplete Cervical Spinal Cord Injury. AB - We recently demonstrated that the electrical perceptual threshold (EPT) examination reveals spared sensory function at lower spinal segments compared with the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) examination in humans with chronic incomplete cervical spinal cord injury (SCI). Here, we investigated whether discrepancies in sensory function detected by both sensory examinations change over time after SCI. Forty five participants with acute (<1 year), chronic (>=1-10 years), and extended chronic (>10 years) incomplete cervical SCI and 30 control subjects were tested on dermatomes C2-T4 bilaterally. EPT values were higher in subjects with acute (2.5 +/- 0.8 mA), chronic (2.2 +/- 0.7 mA), or extended-chronic (2.8 +/- 1.1 mA) SCI compared with controls (1.0 +/- 0.1 mA). The EPT examination detected sensory impairments in spinal segments above (2.3 +/- 0.9) and below (4.2 +/- 2.6) the level detected by the ISNCSCI sensory examination in participants with acute and chronic SCI, respectively. Notably, both examinations detected similar levels of spared sensory function in the extended-chronic phase of SCI (0.8 +/- 0.5). A negative correlation was found between differences in EPT and ISNCSCI sensory levels and time post-injury. These observations indicate that discrepancies between EPT and ISNCSCI sensory scores are time-dependent, with the EPT revealing impaired sensory function above, below, or at the same spinal segment as the ISNCSCI examination. We propose that the EPT is a sensitive tool to assess changes in sensory function over time after incomplete cervical SCI. PMID- 27203698 TI - Myeloid-derived suppressor cells are essential for maintaining feto-maternal immunotolerance via STAT3 signaling in mice. AB - Maternal immune system tolerance to the semiallogeneic fetus is essential for a successful pregnancy; however, the mechanisms underlying this immunotolerance have not been fully elucidated. Here, we demonstrate that myeloid-derived suppressor cells play an important role in maintaining feto-maternal tolerance. A significant expansion of granulocytic myeloid-derived suppressor cells was observed in multiple immune organs and decidual tissues from pregnant mice. Pregnancy-derived granulocytic myeloid-derived suppressor cells suppressed T cell responses in a reactive oxygen species-dependent manner and required direct cell cell contact. Mechanistic studies showed that progesterone facilitated differentiation and activation of granulocytic myeloid-derived suppressor cells, mediated through STAT3 signaling. The STAT3 inhibitor JSI-124 and a specific short hairpin RNA completely abrogated the effects of progesterone on granulocytic myeloid-derived suppressor cells. More importantly, granulocytic myeloid-derived suppressor cell depletion dramatically enhanced the abortion rate in normal pregnant mice, whereas adoptive transfer of granulocytic myeloid derived suppressor cells clearly reduced the abortion rate in the CBA/J X DBA/2J mouse model of spontaneous abortion. These observations collectively demonstrate that granulocytic myeloid-derived suppressor cells play an essential role in the maintenance of fetal immunotolerance in mice. Furthermore, our study supports the notion that in addition to their well-recognized roles under pathologic conditions, myeloid-derived suppressor cells perform important functions under certain physiologic circumstances. PMID- 27203699 TI - Macroelemental composition of cadmium stressed lettuce plants grown under conditions of intensive sulphur nutrition. AB - Lettuce (Lactuca sativa L.) is moderately sensitive to cadmium (Cd) and shows high accumulation of this metal. Thus, this species is considered to be a good model for both identifying determinants controlling Cd accumulation in plant tissues and for developing breeding strategies aimed at limiting the accumulation of this metal in edible tissues. Simultaneously, lettuce is characterised by medium requirements for sulphur (S) - a macronutrient whose role is associated not only with proper growth and development, but also with stress tolerance. The common use of NPK fertilizers without sulphates (S-SO4) together with the progressive process of reducing emissions of S compounds to the natural environment may lead to deficiency of this element in plants. The present study evaluated the changes in macronutrient content and accumulation in Cd-stressed lettuce 'Justyna' supplied with different S doses. Four concentrations of Cd (0, 0.0002, 0.02 or 0.04 mM) and three levels of S applied in the form of S-SO4 (2, 6 or 9 mM S) were used. Cd exposure impaired the macronutrient balance and accumulation in lettuce. Intensive S nutrition to some extent alleviated Cd induced toxicity. High S doses, especially 6 mM S, partially improved macronutrient status and restored the macronutrient balance. In Cd-stressed plants supplemented with additional S, an increase in root and shoot biomass and in the content of N, K and Mg was found, without significant changes in the Ca content. Simultaneously, the P and S contents in the biomass of both above- and underground organs remained unchanged. In the leaves, as opposite to the roots, intensive S nutrition reduced the accumulation of Cd. However, the foliar Cd concentration still exceeded the acceptable limits established for consumption. All the obtained results concerning the content of macronutrients and their ratios were referred, inter alia, to the standards i.e. the Diagnosis and Recommendation Integrated System (DRIS) norms. PMID- 27203700 TI - Influence of forest management systems on natural resource use and provision of ecosystem services in Tanzania. AB - Social, religious and economic facets of rural livelihoods in Sub-Saharan Africa are heavily dependent on natural resources, but improper resource management, drought, and social instability frequently lead to their unsustainable exploitation. In rural Tanzania, natural resources are often governed locally by informal systems of traditional resource management (TRM), defined as cultural practices developed within the context of social and religious institutions over hundreds of years. However, following independence from colonial rule, centralized governments began to exercise jurisdictional control over natural resources. Following decades of mismanagement that resulted in lost ecosystem services, communities demanded change. To improve resource protection and participation in management among stakeholders, the Tanzanian government began to decentralize management programs in the early 2000s. We investigated these two differing management approaches (traditional and decentralized government) in Sonjo communities, to examine local perceptions of resource governance, management influences on forest use, and their consequences for forest and water resources. While 97% of households understood the regulations governing traditionally-managed forests, this was true for only 39% of households for government-managed forests, leading to differences in forest use. Traditional management practices resulted in improved forest condition and surface water quality. This research provides an essential case study demonstrating the importance of TRM in shaping decision frameworks for natural resource planning and management. PMID- 27203701 TI - Consensus of stakeholders on precautionary allergen labelling: A report from the Centre for Food and Allergy Research. PMID- 27203702 TI - Regression and Progression Predictors of CIN2 in Women Younger Than 25 Years. AB - OBJECTIVE: The purpose of this study was to review the management and outcome of cervical intraepithelial neoplasia 2 (CIN2) in women younger than 25 years. METHODS: A retrospective review was performed, investigating women younger than 25 years at the time of diagnosis with biopsy-proven CIN2 between January 1, 2010, and December 31, 2014, who were seen in the colposcopy clinic at the Queen Elizabeth II Hospital in Halifax, Nova Scotia, Canada. The regression, persistence, and progression rate of CIN2 in conservative managed women were evaluated, and potential risk factors were examined. Colposcopy, cytologic, and histopathologic findings were compared with women with immediate treatment (<6 months). RESULTS: Of the 319 women included in the study, 108 women received immediate treatment, and 211 women were managed conservatively; of these, 144 women remained untreated, and 67 women received treatment 6 months or greater. From the women managed conservatively, 150 women (71.1%) showed regression, 26 women (12.3%) had persistent disease, and 35 women (16.6%) progressed, with a median follow-up of 15.1 months. None of the women included in the study progressed to invasive cancer. The hazard ratio for time to progression was 2.40 for women who smoked (p = 0.006). CONCLUSIONS: A conservative approach of CIN2 is the preferred management option for women younger than 25 years. Smoking was identified as a risk factor for progression. PMID- 27203703 TI - Paget Disease of the Vulva: Significance of Surgical Margin Status. PMID- 27203704 TI - The Role of the Male in Preventing HPV-Related Diseases. PMID- 27203705 TI - Surgical Treatment of Paget Disease of the Vulva: Prognostic Significance of Stromal Invasion and Surgical Margin Status. PMID- 27203706 TI - Neutron spectrum measurements at a radial beam port of the NUR research reactor using a Bonner spheres spectrometer. AB - This paper describes the measurement campaign held around the neutron radiography (NR) facility of the Algerian 1MW NUR research reactor. The main objective of this work is to characterize accurately the neutron beam provided at one of the radial channels of the NUR research reactor taking benefit of the acquired CRNA Bonner spheres spectrometer (BSS). The specific objective was to improve the image quality of the NR facility. The spectrometric system in use is based on a central spherical (3)He thermal neutron proportional counter combined with high density polyethylene spheres of different diameters ranging from 3 to 12in. This counting system has good gamma ray discrimination and is able to cover an energy range from thermal to 20MeV. The measurements were performed at the sample distance of 0.6m from the beam port and at a height of 1.2m from the facility floor. During the BSS measurements, the reactor was operating at low power (100W) to avoid large dead times, pulse pileup and high level radiation exposures, in particular, during spheres handling. Thereafter, the neutron spectrum at the sample position was unfolded by means of GRAVEL and MAXED computer codes. The thermal, epithermal and fast neutron fluxes, the total neutron flux, the mean energy and the Cadmium ratio (RCd) were provided. A sensitivity analysis was performed taking into account various defaults spectra and ultimately a different response functions in the unfolding procedure. Overall, from the obtained results it reveals, unexpectedly, that the measured neutron spectrum at the sample position of the neutron radiography of the NUR reactor is being harder with a predominance of fast neutrons (>100keV) by about 60%. Finally, those results were compared to previous and more recent measurements obtained by activation foils detectors. The agreement was fairly good highlighting thereby the consistency of our findings. PMID- 27203707 TI - Phylogenetic relationships and protein modelling revealed two distinct subfamilies of group II HKT genes between crop and model grasses. AB - Molecular evolution of large protein families in closely related species can provide useful insights on structural functional relationships. Phylogenetic analysis of the grass-specific group II HKT genes identified two distinct subfamilies, I and II. Subfamily II was represented in all species, whereas subfamily I was identified only in the small grain cereals and possibly originated from an ancestral gene duplication post divergence from the coarse grain cereal lineage. The core protein structures were highly analogous despite there being no more than 58% amino acid identity between members of the two subfamilies. Distinctly variable regions in known functional domains, however, indicated functional divergence of the two subfamilies. The subsets of codons residing external to known functional domains predicted signatures of positive Darwinian selection potentially identifying new domains of functional divergence and providing new insights on the structural function and relationships between protein members of the two subfamilies. PMID- 27203708 TI - Surgical management of congenital torticollis in children older than 7 years with an average 10-year follow-up. AB - The aim of the present study is to present the results of the surgical management of late presenting cases of congenital muscular torticollis. Between 1990 and 2010, 31 cases of late presenting congenital muscular torticollis were managed surgically in our department. Postoperatively, head halter traction was applied for 10 days; a cervical brace was applied for 5 weeks, followed by a soft one collar for 3 months. The final result was assessed on the basis of the criteria of Cheng and Tang. In total, 84% of patients achieved an excellent final result and 16% of the patients achieved a good result. Our results indicated that in children older than 7 years, surgical release combined with appropriate orthosis and a structured physiotherapy regime can lead to satisfactory results. PMID- 27203709 TI - Engineering Enriched Microenvironments with Gradients of Platelet Lysate in Hydrogel Fibers. AB - Gradients of physical and chemical cues are characteristic of specific tissue microenvironments and contribute toward morphogenesis and tissue regeneration upon injury. Recent advances on microfluidics and hydrogel manipulation raised the possibility of generating biomimetic biomaterials enriched with bioactive factors and encapsulating cells following designs specifically tailored for a target application. The novelty of this work relies on the combination of methacrylated gellan gum (MeGG) with platelet lysate (PL), aiming to generate novel advanced 3D PL-enriched photo-cross-linkable hydrogels and overcoming the lack of adhesion sites provided by the native MeGG hydrogels. This combination takes advantage of the availability, enriched growth factor composition, and potential autologous application of PL while simultaneously preserving the ability provided by MeGG to tailor mechanical properties, protein release kinetics, and shape of the construct according to the desired goal. Incorporation of PL in the hydrogels significantly improved cellular adhesion and viability in the constructs. The use of microfluidic tools allowed the design of a fiber-like hydrogel incorporating a gradient of PL along the length of the fiber. These spatial protein gradients led to the viability and cell number gradients caused by maintenance of human umbilical vein endothelial cells (HUVECs) survival in the fibers toward the PL-enriched sections in comparison with the nonloaded MeGG sections of the fibers. Altogether, we propose a proof of concept strategy to design a PL gradient biomaterial with potential in tissue engineering approaches and analysis of cell-microenvironment interactions. PMID- 27203710 TI - Summation of slow motor unit forces at constant and variable interpulse intervals in rat soleus muscle. AB - Effects of the summation of forces generated by functionally isolated slow-twitch motor units (MU) of the rat soleus muscle were examined in this study. Initially, the twitch, fused tetanic and unfused tetanic contractions evoked by trains of stimuli at variable interpulse intervals were recorded for each MU. Then, two, three or four MUs were co-activated, and the recorded forces were compared to the algebraic sum of the forces of individual MUs. The mean cumulative force of twitches and the mean cumulative force of fused tetani were not statistically different from the respective algebraic sums of forces, which revealed a high degree of linearity in the summation. However, relaxation of the recorded tetanic contractions (either fused or unfused) was faster than that predicted by the linear summation of individual contractions. Moreover, for twitch and tetanic contractions, a tendency to shorten relaxation with an increasing number of co active MUs was noted. The results indicate that forces of rat soleus slow MUs sum up more linearly than in the respective cat muscle as well as more linearly than for fast MUs in the medial gastrocnemius muscle. PMID- 27203711 TI - Hp: an inflammatory indicator in cardiovascular disease. AB - Over the past decade significant advancement has occurred in the biological and pathological role that Hp has in cardiovascular disease. Hp is an acute-phase protein with a role in the neutralization and clearance of free heme. Iron has tremendous potential for initiating vascular oxidation, inflammation and exacerbating coronary atherosclerosis. Hp genotype has been linked as a prognostic biomarker of acute myocardial infarction, heart failure, restenosis and cardiac transplant rejection. The increased understanding of Hp as a biomarker has provided new insights into the mechanisms of inflammation after cardiac injury and support the concept that Hp is not only an important antioxidant in vascular inflammation and atherosclerosis, but also an enhancer of inflammation in cardiac transplant. PMID- 27203712 TI - Correction: Measuring Fisher Information Accurately in Correlated Neural Populations. AB - [This corrects the article DOI: 10.1371/journal.pcbi.1004218.]. PMID- 27203713 TI - Single Molecule Discrimination of Heteropolytungstates and Their Isomers in Solution with a Nanometer-Scale Pore. AB - We report a new method to identify metallic nanoclusters (polyoxometalate structures) in solution at the single molecule limit using a nanometer-scale pore. The technique allows the measurement of polyoxometalates with over 2 orders of magnitude lower analyte concentration than conventional analytical chemistry tools. Furthermore, pH-dependent structural changes in phosphotungstic acid are measured with protein nanopores and validated with NMR. We further demonstrate that the method can also discriminate [PW9O34](9-) structural isomers. The results suggest this technique can serve as a complementary approach to traditional methods. PMID- 27203714 TI - Cardiovascular disease risk scores' relationship to subclinical cardiovascular disease among HIV-infected and HIV-uninfected men. AB - OBJECTIVE: To study cardiovascular disease risk score utility, we compared the association between Framingham Risk Score (FRS)/pooled cohort equation (PCE) categories and coronary artery plaque presence by HIV serostatus and evaluated whether D : A : D risk category more accurately identifies plaque in HIV-infected men. DESIGN: Cross-sectional analysis within a substudy of the Multicenter AIDS Cohort Study. METHODS: Cardiac computed tomography was performed to assess coronary plaque. We evaluated the association of plaque with increasing cardiovascular disease risk score category, stratified by HIV serostatus, using logistic regression. Receiver operating characteristic curves compared the discrimination of the scores for plaque by HIV serostatus. The sensitivity and specificity of the risk scores were compared in HIV-infected men. RESULTS: The risk score category - plaque associations were stronger among HIV-uninfected men than HIV-infected men, except for noncalcified plaque. For example, the odds of coronary artery calcium more than 0 were 7.03 (95% confidence interval 4.21, 11.76) times greater among men in the PCE high-risk versus low-risk category among HIV-uninfected men, compared with just 3.13 (95% confidence interval 2.13, 4.61) times greater among men in the high-risk versus low-risk category among HIV infected men. Among HIV-infected men, high-risk category by PCE identified the greatest percentage of men with plaque/stenosis, but with lower specificity than D : A : D and FRS. The prevalence of coronary artery calcium more than 0 among men in the PCE low-risk category was 26.5% (HIV-uninfected men) and 36.0% (HIV infected men). CONCLUSIONS: FRS and PCE categories associate with plaque burden better in HIV-uninfected men. No risk score delivered both high sensitivity and specificity among HIV-infected men. PMID- 27203715 TI - Rosuvastatin slows progression of subclinical atherosclerosis in patients with treated HIV infection. AB - OBJECTIVE: To determine the effect of statins on the progression of subclinical atherosclerosis in a population of HIV-infected adults on antiretroviral therapy. DESIGN: Double-blind, randomized clinical trial. METHODS: Stopping Atherosclerosis and Treating Unhealthy Bone with RosuvastatiN in HIV infection was a 96-week double-blind, randomized clinical trial of 10 mg daily rosuvastatin (n = 72) vs. placebo (n = 75) in a population of HIV-infected subjects on stable antiretroviral therapy with LDL-cholesterol 130 mg/dl or less (<=3.36 mmol/l) and evidence of heightened T-cell activation (CD8CD38HLA-DR >=19%) or increased inflammation [high sensitivity C-reactive protein >=2 mg/l (>=19 mmol/l)]. Change in common carotid artery intima-media thickness (IMT) (CCA-IMT) was the primary outcome. Secondary outcomes were changes in LDL and coronary artery calcium. RESULTS: Median (Q1, Q3) age was 46 (40, 53) years; 78% were man and 68% African American; 49% were on a protease inhibitor. Mean (95% confidence interval) change in LDL was -21 (-27 to -15) mg/dl [-0.54 (-0.70 to -0.39) mmol/l] in the rosuvastatin arm. In a multivariable linear mixed-effects model, assignment to statin was associated with 0.019 mm (95% confidence interval: 0.002-0.037 mm) less progression of CCA-IMT over 96 weeks. We did not find substantial effect modification by level of inflammation or immune activation biomarkers, except for a borderline statistically significant interaction for soluble vascular cell adhesion molecule (P = 0.065). There was no difference in coronary artery calcium change (P = 0.61). CONCLUSION: Rosuvastatin effectively lowers LDL and appears to substantially slow progression of CCA-IMT in patients with treated HIV infection. Future study is needed to determine whether subjects with higher levels of inflammation or immune activation derive greater cardiovascular benefit from statin therapy. PMID- 27203717 TI - Transparency in Biomedical Research: Evidence-Based Reporting Guidelines. PMID- 27203716 TI - Self-selection of male circumcision clients and behaviors following circumcision in a service program in Uganda. AB - OBJECTIVES: Sub-Saharan African countries have substantially scaled-up safe male circumcision (SMC) services. However, it is unclear whether services are reaching men most at risk of HIV and whether there is behavioral disinhibition after SMC. We compared characteristics of SMC acceptors and nonacceptors in Rakai, Uganda. DESIGN: Cohort design. METHODS: Through the Rakai Community Cohort Study, baseline characteristics of 587 non-Muslim men who subsequently accepted SMC were compared with those of 4907 uncircumcised non-Muslim men. Behaviors after SMC were compared with those of men who remained uncircumcised. Poisson multivariable regression was used to estimate adjusted prevalence rate ratios of behaviors in circumcised versus uncircumcised men. RESULTS: At baseline (pre-SMC), men subsequently circumcised were younger (mean = 26.1 years), as compared with the uncircumcised (mean = 28.5 years, P < 0.001), more likely to live in urban areas (21.1 versus 12.4%, P < 0.001), less likely to have been currently or previously married (36.5 versus 45.8%, P < 0.001) and more likely to report multiple sexual partners (48.3 versus 41.6%, P = 0.05) and genital discharge (7.4 versus 4.4%, P = 0.03). At follow-up (post-SMC), behaviors and genital discharge did not differ between the groups. Genital ulcers were less reported among circumcised (6.8%) compared with uncircumcised men (10.5%; adjusted prevalence rate ratios = 0.60, 95% confidence interval = 0.42-0.87, P = 0.007). CONCLUSION: In Rakai district, Uganda, the circumcision service program is attracting sexually active men at higher risk of HIV and we find no evidence of behavioral disinhibition following circumcision. The SMC program in this setting has the potential to reduce the HIV epidemic among men. PMID- 27203720 TI - Organ Dose and Attributable Cancer Risk in Lung Cancer Screening with Low-Dose Computed Tomography. AB - PURPOSE: Lung cancer screening with CT has been recently recommended for decreasing lung cancer mortality. The radiation dose of CT, however, must be kept as low as reasonably achievable for reducing potential stochastic risks from ionizing radiation. The purpose of this study was to calculate individual patients' lung doses and to estimate cancer risks in low-dose CT (LDCT) in comparison with a standard dose CT (SDCT) protocol. MATERIALS AND METHODS: This study included 47 adult patients (mean age 63.0 +/- 5.7 years) undergoing chest CT on a third-generation dual-source scanner. 23/47 patients (49%) had a non enhanced chest SDCT, 24 patients (51%) underwent LDCT at 100 kVp with spectral shaping at a dose equivalent to a chest x-ray. 3D-dose distributions were obtained from Monte Carlo simulations for each patient, taking into account their body size and individual CT protocol. Based on the dose distributions, patient specific lung doses were calculated and relative cancer risk was estimated according to BEIR VII recommendations. RESULTS: As compared to SDCT, the LDCT protocol allowed for significant organ dose and cancer risk reductions (p<0.001). On average, lung dose was reduced from 7.7 mGy to 0.3 mGy when using LDCT, which was associated with lowering of the cancer risk from 8.6 to 0.35 per 100'000 cases. A strong linear correlation between lung dose and patient effective diameter was found for both protocols (R2 = 0.72 and R2 = 0.75 for SDCT and LDCT, respectively). CONCLUSION: Use of a LDCT protocol for chest CT with a dose equivalent to a chest x-ray allows for significant lung dose and cancer risk reduction from ionizing radiation. PMID- 27203722 TI - Circles of support and accountability: The characteristics of core members in England and Wales. AB - BACKGROUND: Circles of support and accountability, or Circles, use community volunteers to help reintegrate sex offenders at risk of reoffending in the community. AIMS: The aims of this study are to describe the first 275 male sex offenders ('core members') in England and Wales supported by a Circle and to compare those attending the five largest Circles. METHODS: As part of their monitoring activity, 10 Circles extracted data from case files, anonymised it and submitted it to Circles UK, the national oversight body. RESULTS: Circles have expanded rapidly with 165 (60%) of Circles commencing in the three years 2011 2013 compared with 110 in the nine years 2002-2010. Most core members were referred from the Probation Service (82%). Circles were provided to men with a range of predicted risks of reoffending - from low (26%) to very high (12%). There were some positive changes between the beginning and end of Circles, such as fewer men being unemployed and more living in their own chosen accommodation. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Circles have been used to support the reintegration of a wide range of sex offenders. Given their rapid growth and flexibility, consistent recording standards are required across. These standards should be reviewed periodically to ensure all important fields of change are captured, including frequency of attendance, length per session and quality of engagement in the work. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27203721 TI - Australian Cattle Dogs with Neuronal Ceroid Lipofuscinosis are Homozygous for a CLN5 Nonsense Mutation Previously Identified in Border Collies. AB - BACKGROUND: Neuronal ceroid lipofuscinosis (NCL), a fatal neurodegenerative disease, has been diagnosed in young adult Australian Cattle Dogs. OBJECTIVE: Characterize the Australian Cattle Dog form of NCL and determine its molecular genetic cause. ANIMALS: Tissues from 4 Australian Cattle Dogs with NCL-like signs and buccal swabs from both parents of a fifth affected breed member. Archived DNA samples from 712 individual dogs were genotyped. METHODS: Tissues were examined by fluorescence, electron, and immunohistochemical microscopy. A whole-genome sequence was generated for 1 affected dog. A TaqMan allelic discrimination assay was used for genotyping. RESULTS: The accumulation of autofluorescent cytoplasmic storage material with characteristic ultrastructure in tissues from the 4 affected dogs supported a diagnosis of NCL. The whole-genome sequence contained a homozygous nonsense mutation: CLN5:c.619C>T. All 4 DNA samples from clinically affected dogs tested homozygous for the variant allele. Both parents of the fifth affected dog were heterozygotes. Archived DNA samples from 346 Australian Cattle Dogs, 188 Border Collies, and 177 dogs of other breeds were homozygous for the reference allele. One archived Australian Cattle Dog sample was from a heterozygote. CONCLUSIONS AND CLINICAL IMPORTANCE: The homozygous CLN5 nonsense is almost certainly causal because the same mutation previously had been reported to cause a similar form of NCL in Border Collies. Identification of the molecular genetic cause of Australian Cattle Dog NCL will allow the use of DNA tests to confirm the diagnosis of NCL in this breed. PMID- 27203724 TI - Nanoscale Synthesis of Two Porphyrin-Based MOFs with Gallium and Indium. AB - Two porphyrin-based metal-organic frameworks (MOFs) containing gallium or indium, [Ga2(OH)2(H2TCPP)].3DMF.3H2O (Ga-PMOF) and [In2(OH)2(H2TCPP)].3DMF.4H2O (In-PMOF) (H6TCPP = 4-tetracarboxyphenylporphyrin), were discovered using high-throughput methods. The structure was refined by the Rietveld-method starting from the structure model of Al-PMOF, [Al2(OH)2(H2TCPP)]. The new PMOFs exhibit BET surface areas between 1150 and 1400 m(2) g(-1) and are also porous toward CO2 (Ga-PMOF, 15.2 wt %; In-PMOF, 12.9 wt %). They are thermally stable in air up to 330 degrees C, but show limited chemical stabilities toward acids and bases. In order to achieve size control, different synthesis routes were investigated, i.e., batch synthesis at different temperatures (yield: In-PMOF-bs-th 96%, Ga-PMOF-bs th 87%), ultrasound-assisted synthesis (yield: In-PMOF-bs-us 85%), and continuous flow synthesis (yield: Ga-PMOF-cf 71%). By using these different methods we could control the nucleation rate and the crystal size. The crystal sizes were found to vary about 60 to 160 nm and 70 to 130 nm for Ga- and In-PMOF, respectively, which was proven by dynamic light scattering (DLS), powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) measurements. PMID- 27203723 TI - Mass Spectrometric-Based Selected Reaction Monitoring of Protein Phosphorylation during Symbiotic Signaling in the Model Legume, Medicago truncatula. AB - Unlike the major cereal crops corn, rice, and wheat, leguminous plants such as soybean and alfalfa can meet their nitrogen requirement via endosymbiotic associations with soil bacteria. The establishment of this symbiosis is a complex process playing out over several weeks and is facilitated by the exchange of chemical signals between these partners from different kingdoms. Several plant components that are involved in this signaling pathway have been identified, but there is still a great deal of uncertainty regarding the early events in symbiotic signaling, i.e., within the first minutes and hours after the rhizobial signals (Nod factors) are perceived at the plant plasma membrane. The presence of several protein kinases in this pathway suggests a mechanism of signal transduction via posttranslational modification of proteins in which phosphate is added to the hydroxyl groups of serine, threonine and tyrosine amino acid side chains. To monitor the phosphorylation dynamics and complement our previous untargeted 'discovery' approach, we report here the results of experiments using a targeted mass spectrometric technique, Selected Reaction Monitoring (SRM) that enables the quantification of phosphorylation targets with great sensitivity and precision. Using this approach, we confirm a rapid change in the level of phosphorylation in 4 phosphosites of at least 4 plant phosphoproteins that have not been previously characterized. This detailed analysis reveals aspects of the symbiotic signaling mechanism in legumes that, in the long term, will inform efforts to engineer this nitrogen-fixing symbiosis in important non-legume crops such as rice, wheat and corn. PMID- 27203725 TI - Regional lung function determined by electrical impedance tomography during bronchodilator reversibility testing in patients with asthma. AB - The measurement of rapid regional lung volume changes by electrical impedance tomography (EIT) could determine regional lung function in patients with obstructive lung diseases during pulmonary function testing (PFT). EIT examinations carried out before and after bronchodilator reversibility testing could detect the presence of spatial and temporal ventilation heterogeneities and analyse their changes in response to inhaled bronchodilator on the regional level. We examined seven patients suffering from chronic asthma (49 +/- 19 years, mean age +/- SD) using EIT at a scan rate of 33 images s(-1) during tidal breathing and PFT with forced full expiration. The patients were studied before and 5, 10 and 20 min after bronchodilator inhalation. Seven age- and sex matched human subjects with no lung disease history served as a control study group. The spatial heterogeneity of lung function measures was quantified by the global inhomogeneity indices calculated from the pixel values of tidal volume, forced expiratory volume in one second (FEV1), forced vital capacity (FVC), peak flow and forced expiratory flow between 25% and 75% of FVC as well as histograms of pixel FEV1/FVC values. Temporal heterogeneity was assessed using the pixel values of expiration times needed to exhale 75% and 90% of pixel FVC. Regional lung function was more homogeneous in the healthy subjects than in the patients with asthma. Spatial and temporal ventilation distribution improved in the patients with asthma after the bronchodilator administration as evidenced mainly by the histograms of pixel FEV1/FVC values and pixel expiration times. The examination of regional lung function using EIT enables the assessment of spatial and temporal heterogeneity of ventilation distribution during bronchodilator reversibility testing. EIT may become a new tool in PFT, allowing the estimation of the natural disease progression and therapy effects on the regional and not only global level. PMID- 27203727 TI - Quantum Mechanical Description of Raman Scattering from Molecules in Plasmonic Cavities. AB - Plasmon-enhanced Raman scattering can push single-molecule vibrational spectroscopy beyond a regime addressable by classical electrodynamics. We employ a quantum electrodynamics (QED) description of the coherent interaction of plasmons and molecular vibrations that reveal the emergence of nonlinearities in the inelastic response of the system. For realistic situations, we predict the onset of phonon-stimulated Raman scattering and a counterintuitive dependence of the anti-Stokes emission on the frequency of excitation. We further show that this QED framework opens a venue to analyze the correlations of photons emitted from a plasmonic cavity. PMID- 27203726 TI - A Two-Year Review on Epidemiology and Clinical Characteristics of Dengue Deaths in Malaysia, 2013-2014. AB - BACKGROUND: Dengue infection is the fastest spreading mosquito-borne viral disease, which affects people living in the tropical and subtropical countries. Malaysia had large dengue outbreaks in recent years. We aimed to study the demographics and clinical characteristics associated with dengue deaths in Malaysia. METHODS: We conducted a retrospective review on all dengue deaths that occurred nationwide between 1st January 2013 and 31st December 2014. Relevant data were extracted from mortality review reports and investigational forms. These cases were categorized into children (<15 years), adults (15-59 years) and elderly (>=60 years) to compare their clinical characteristics. RESULTS: A total of 322 dengue deaths were reviewed. Their mean age was 40.7+/-19.30 years, half were females and 72.5% were adults. The median durations of first medical contact, and hospitalization were 1 and 3 days, respectively. Diabetes and hypertension were common co-morbidities among adults and elderly. The most common warning signs reported were lethargy and vomiting, with lethargy (p = 0.038) being more common in children, while abdominal pain was observed more often in the adults (p = 0.040). But 22.4% did not have any warning signs. Only 34% were suspected of dengue illness at their initial presentation. More adults developed severe plasma leakage (p = 0.018). More than half (54%) suffered from multi-organ involvement, and 20.2% were free from any organ involvement. Dengue deaths occurred at the median of 3 days post-admission. Dengue shock syndrome (DSS) contributed to more than 70% of dengue deaths, followed by severe organ involvement (69%) and severe bleeding (29.7%). CONCLUSION: In Malaysia, dengue deaths occurred primarily in adult patients. DSS was the leading cause of death, regardless of age groups. The atypical presentation and dynamic progression of severe dengue in this cohort prompts early recognition and aggressive intervention to prevent deaths. TRIAL REGISTRATION: National Medical Research Registry (NMRR, NMRR-14-1374-23352). PMID- 27203728 TI - Zinc Finger Domain of the PRDM9 Gene on Chromosome 1 Exhibits High Diversity in Ruminants but Its Paralog PRDM7 Contains Multiple Disruptive Mutations. AB - PRDM9 is the sole hybrid sterility gene identified so far in vertebrates. PRDM9 gene encodes a protein with an immensely variable zinc-finger (ZF) domain that determines the site of meiotic recombination hotspots genome-wide. In this study, the terminal ZF domain of PRDM9 on bovine chromosome 1 and its paralog on chromosome 22 were characterized in 225 samples from five ruminant species (cattle, yak, mithun, sheep and goat). We found extraordinary variation in the number of PRDM9 zinc fingers (6 to 12). We sequenced PRDM9 ZF encoding region from 15 individuals (carrying the same ZF number in both copies) and found 43 different ZF domain sequences. Ruminant zinc fingers of PRDM9 were found to be diversifying under positive selection and concerted evolution, specifically at positions involved in defining their DNA-binding specificity, consistent with the reports from other vertebrates such as mice, humans, equids and chimpanzees. ZF encoding regions of the PRDM7, a paralog of PRDM9 on bovine chromosome 22 and on unknown chromosomes in other studied species were found to contain 84 base repeat units as in PRDM9, but there were multiple disruptive mutations after the first repeat unit. The diversity of the ZFs suggests that PRDM9 may activate recombination hotspots that are largely unique to each ruminant species. PMID- 27203729 TI - Serotonin-containing neurons in basal insects: In search of ground patterns among tetraconata. AB - The ventral nerve cord of Tetraconata contains a comparably low number of serotonin-immunoreactive neurons, facilitating individual identification of cells and their characteristic neurite morphology. This offers the rather unique possibility of establishing homologies at the single cell level. Because phylogenetic relationships within Tetraconata are still discussed controversially, comparisons of individually identifiable neurons can help to unravel these issues. Serotonin immunoreactivity has been investigated in numerous tetraconate taxa, leading to reconstructions of hypothetical ground patterns for major lineages. However, detailed descriptions of basal insects are still missing, but are crucial for meaningful evolutionary considerations. We investigated the morphology of individually identifiable serotonin-immunoreactive neurons in the ventral nerve cord of Zygentoma (Thermobia domestica, Lepisma saccharina, Atelura formicaria) and Archaeognatha (Machilis germanica, Dilta hibernica). To improve immunocytochemical resolution, we also performed preincubation experiments with 5-hydroxy-L-tryptophan and serotonin. Additionally, we checked for immunolabeling of tryptophan hydroxylase, an enzyme associated with the synthesis of serotonin. Besides the generally identified groups of anterolateral, medial, and posterolateral neurons within each ganglion of the ventral nerve cord, we identified several other immunoreactive cells, which seem to have no correspondence in other tetraconates. Furthermore, we show that not all immunoreactive neurons produce serotonin, but have the capability for serotonin uptake. Comparisons with the patterns of serotonin-containing neurons in major tetraconate taxa suggest a close phylogenetic relationship of Remipedia, Cephalocarida, and Hexapoda, supporting the Miracrustacea hypothesis. J. Comp. Neurol., 2016. (c) 2016 Wiley Periodicals, Inc. J. Comp. Neurol. 525:79 115, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27203730 TI - As Opioid Prescribing Guidelines Tighten, Mindfulness Meditation Holds Promise for Pain Relief. PMID- 27203731 TI - [Histological Techniques]. PMID- 27203732 TI - [Cosmetic Eyelid Surgery]. PMID- 27203733 TI - [Anaesthesia in Ophthalmic Surgery]. PMID- 27203735 TI - Surface CuO, Bi2O3, and CeO2 Species Supported in TiO2-Anatase: Study of Interface Effects in Toluene Photodegradation Quantum Efficiency. AB - The enhancement of active triggered by surface deposition of Cu, Bi, and Ce containing oxidic species onto a high surface area anatase is analyzed through the calculation of the quantum efficiency for toluene photodegradation under UV and Sunlight-type illumination. To this end, series of Cu, Bi, and Ce containing oxides supported on anatase were synthesized having a growing content of the Cu, Bi, and Ce surface species and characterized with X-ray diffraction and photoelectron, UV-visible, and photoluminescence spectroscopies as well as transmission electron microscopy. Utilizing the surface concentration of Cu, Bi, and Ce species as a tool, we analyzed the influence of the system physicochemical properties affecting quantum efficiency in anatase-based materials. First, employing small surface concentrations of the Cu, Bi, and Ce species deposited onto (the unperturbed) anatase, we provided evidence that all steps of the photocatalytic event, including light absorption, charge recombination, as well as surface interaction with the pollutant and chemical output as to activity and selectivity have significance in the quantitative assessment of the enhancement of the efficiency parameter. Second, we analyzed samples rendering maximum quantum efficiency within all these series of materials. The study indicates that maximum enhancement over anatase displays a magnitude strongly dependent on the efficiency level of calculation and would thus require the use of the most accurate one, and that it occurs through a balance between optoelectronic and chemical properties of the composite materials. The (Cu, Bi, Ce) oxide-anatase interface plays a major role modulating the optoelectronic properties of the solids and thus the efficiency observable. PMID- 27203734 TI - Pharmacokinetics, efficacy, and safety of a plasma-derived VWF/FVIII concentrate (VONCENTO) for on-demand and prophylactic treatment in patients with von Willebrand disease (SWIFT-VWD study). AB - VONCENTO (CSL Behring Gmbh, Marburg, Germany) is a plasma-derived, high concentration, lower volume [relative to HAEMATE P (CSL Behring)], high-purity von Willebrand factor (VWF)/factor VIII (FVIII) concentrate with a VWF/FVIII ratio similar to HAEMATE P. This open-label, multicentre study investigated the pharmacokinetic, haemostatic efficacy, and safety profiles of VONCENTO in study participants at least 12 years of age with von Willebrand disease (VWD) who required treatment of nonsurgical bleeding (NSB) events or underwent surgery or prophylaxis. The first 12-month on-demand treatment period comprised a pharmacokinetic investigation and an efficacy analysis. After 12 months, qualifying study participants were switched to prophylactic therapy and included in a further 12-month efficacy analysis. In total, 21 study participants (including three adolescents, and 13 study participants with VWD type 3) received VONCENTO as on-demand treatment for 12 months. 'Excellent'/'good' haemostatic efficacy was achieved in 98.3% of the 407 NSB events assessed by investigators. Following the switch to prophylactic treatment, the total number of NSBs in eight patients markedly decreased from 304 to 10 (with haemostatic efficacy judged to be 'excellent' for all). The annualised bleeding rate also significantly decreased from a median of 26.5 events to one event. Safety assessments showed no inhibitory antibodies to either FVIII or VWF, no transmission of infectious agents, no thromboembolic events and no treatment-related serious adverse events. VONCENTO was shown to be well tolerated and provided excellent haemostatic efficacy in the treatment of bleeds or during prophylaxis in study participants with VWD, including also those with type 3, the severest form of VWD. PMID- 27203736 TI - Site-Specific Modulation of Charge Controls the Structure and Stimulus Responsiveness of Intrinsically Disordered Peptide Brushes. AB - Intrinsically disordered proteins (IDPs) are an important and emerging class of materials for tailoring biointerfaces. While the importance of chain charge and resultant electrostatic interactions in controlling conformational properties of IDPs is beginning to be explored through in silico approaches, there is a dearth of experimental studies motivated toward a systematic study of these effects. In an effort to explore this relationship, we measured the conformations of two peptides derived from the intrinsically disordered neurofilament (NF) side arm domain: one depicting the wild-type sequence with four lysine-serine-proline repeats (KSP peptide) and another in which the serine residues were replaced with aspartates (KDP peptide), a strategy sometimes used to mimic phosphorylation. Using a variety of biophysical measurements including a novel application of scanning angle interference microscopy, we demonstrate that the KDP peptide assumes comparatively more expanded conformations in solution and forms significantly thicker brushes when immobilized on planar surfaces at high densities. In both settings, the peptides respond to changes in ambient ionic strength, with each peptide showing distinct stimulus-responsive characteristics. While the KDP peptide undergoes compaction with increasing ionic strength as would be expected for a polyampholyte, the KSP peptide shows biphasic behavior, with an initial compaction followed by an expanded state at a higher ionic strength. Together these results support the notion that modulation of charge on IDPs can regulate conformational and interfacial properties. PMID- 27203737 TI - The Feasibility of Developing an Inpatient Acupuncture Program at a Tertiary Care Pediatric Hospital. AB - OBJECTIVES: Use of complementary and integrative health approaches has increased significantly in recent decades, with hospital-based acupuncture programs becoming more common. This article presents the feasibility of developing an inpatient acupuncture program at a pediatric hospital. DESIGN AND SETTING: In January 2014, Seattle Children's Hospital, a tertiary care pediatric hospital serving patients from a five-state region, began a 6-month pilot project offering inpatient acupuncture. During the pilot, inpatient acupuncture and related manual therapies were provided to pediatric patients age 0-23 years who were admitted to Seattle Children's Hospital or were seen for an outpatient surgical procedure. MEASURES: The following data were collected: the reason for the acupuncture consult, type and number of treatments provided, any reported response to treatment, and any reported adverse events. Patients and referring providers gave feedback via questionnaires. RESULTS: During the pilot program, 338 treatments were provided to 87 patients. High interest, demand, and positive feedback from hospital providers, patients, and families led to the development of a full-time inpatient acupuncture program. CONCLUSIONS: The positive response to Seattle Children's inpatient acupuncture program with feasibility and acceptability demonstrated by increasing consults and patient and provider questionnaire data suggest that similar programs may be of interest to other pediatric hospitals. PMID- 27203738 TI - Targeted next generation sequencing of endoscopic ultrasound acquired cytology from ampullary and pancreatic adenocarcinoma has the potential to aid patient stratification for optimal therapy selection. AB - BACKGROUND & AIMS: Less than 10% of registered drug intervention trials for pancreatic ductal adenocarcinoma (PDAC) include a biomarker stratification strategy. The ability to identify distinct mutation subsets via endoscopic ultrasound fine needle aspiration (EUS FNA) molecular cytology could greatly aid clinical trial patient stratification and offer predictive markers. We identified chemotherapy treatment naive ampullary adenocarcinoma and PDAC patients who underwent EUS FNA to assess multigene mutational frequency and diversity with a surgical resection concordance assessment, where available. METHODS: Following strict cytology smear screening criteria, targeted next generation sequencing (NGS) using a 160 cancer gene panel was performed. RESULTS: Complete sequencing was achieved in 29 patients, whereby 83 pathogenic alterations were identified in 21 genes. Cytology genotyping revealed that the majority of mutations were identified in KRAS (93%), TP53 (72%), SMAD4 (31%), and GNAS (10%). There was 100% concordance for the following pathogenic alterations: KRAS, TP53, SMAD4, KMT2D, NOTCH2, MSH2, RB1, SMARCA4, PPP2R1A, PIK3R1, SCL7A8, ATM, and FANCD2. Absolute multigene mutational concordance was 83%. Incremental cytology smear mutations in GRIN2A, GATA3 and KDM6A were identified despite re-examination of raw sequence reads in the corresponding resection specimens. CONCLUSIONS: EUS FNA cytology genotyping using a 160 cancer gene NGS panel revealed a broad spectrum of pathogenic alterations. The fidelity of cytology genotyping to that of paired surgical resection specimens suggests that EUS FNA represents a suitable surrogate and may complement the conventional stratification criteria in decision making for therapies and may guide future biomarker driven therapeutic development. PMID- 27203739 TI - Radiobiological modeling of two stereotactic body radiotherapy schedules in patients with stage I peripheral non-small cell lung cancer. AB - This study aims to compare the radiobiological response of two stereotactic body radiotherapy (SBRT) schedules for patients with stage I peripheral non-small cell lung cancer (NSCLC) using radiobiological modeling methods. Volumetric modulated arc therapy (VMAT)-based SBRT plans were designed using two dose schedules of 1 * 34 Gy (34 Gy in 1 fraction) and 4 * 12 Gy (48 Gy in 4 fractions) for 19 patients diagnosed with primary stage I NSCLC. Dose to the gross target volume (GTV), planning target volume (PTV), lung and chest wall (CW) were converted to biologically equivalent dose in 2 Gy fraction (EQD2) for comparison. Five different radiobiological models were employed to predict the tumor control probability (TCP) value. Three additional models were utilized to estimate the normal tissue complication probability (NTCP) value for the lung and the modified equivalent uniform dose (mEUD) value to the CW. Our result indicates that the 1 * 34 Gy dose schedule provided a higher EQD2 dose to the tumor, lung and CW. Radiobiological modeling revealed that the TCP value for the tumor, NTCP value for the lung and mEUD value for the CW were 7.4% (in absolute value), 7.2% (in absolute value) and 71.8% (in relative value) higher on average, respectively, using the 1 * 34 Gy dose schedule. PMID- 27203740 TI - MiR-193a-5p/ERBB2 act as concurrent chemoradiation therapy response indicator of esophageal squamous cell carcinoma. AB - Concurrent chemoradiation therapy (CCRT) is the predominant treatment in esophageal cancer, however resistance to therapy and tumor recurrence are exceedingly common. Elevated ERBB2/Her2 may be at least partially responsible for both the high rates of recurrence and resistance to CCRT. This receptor tyrosine kinase is upregulated in 10-20% of esophageal squamous cell carcinoma (ESCC) tissues, and amplification of ERBB2 has been correlated with poor prognosis in esophageal cancer. Tissues from 131 ESCC patients, along with cell and animal models of the disease were used to probe the underlying mechanisms by which ERBB2 upregulation occurs and causes negative outcomes in ESCC. We found that overexpression of ERBB2 inhibited radiosensitivity in vitro. Furthermore, miR 193a-5p reduced ERBB2 expression by directly targeting the 3'UTR. Increased miR 193a-5p enhanced radiosensitivity and inhibited tumorigenesis in vitro and in vivo. Additionally, low miR-193a-5p expression correlated with poor prognosis in ESCC patients, and ESCC patients with good CCRT response exhibited higher miR 193a-5p expression. Our data suggest that patients with high miR-193a-5p will likely benefit from CCRT treatment alone, however a combination of CCRT with Herceptin may be beneficial for patients with low miR-193a-5p expression. PMID- 27203741 TI - Metastatic site-specific polarization of macrophages in intracranial breast cancer metastases. AB - In contrast to primary tumors, the understanding of macrophages within metastases is very limited. In order to compare macrophage phenotypes between different metastatic sites, we established a pre-clinical mouse model of intracranial breast cancer metastasis in which cancer lesions develop simultaneously within the brain parenchyma and the dura. This mimics a situation that is commonly occurring in the clinic. Flow cytometry analysis revealed significant differences in the activation state of metastasis-associated macrophages (MAMs) at the two locations. Concurrently, gene expression analysis identified significant differences in molecular profiles of cancer cells that have metastasized to the brain parenchyma as compared to the dura. This included differences in inflammation-related pathways, NF-kB1 activity and cytokine profiles. The most significantly upregulated cytokine in brain parenchyma- versus dura-derived cancer cells was Lymphotoxin beta and a gain-of-function approach demonstrated a direct involvement of this factor in the M2 polarization of parenchymal MAMs. This established a link between metastatic site-specific properties of cancer cells and the MAM activation state. PMID- 27203743 TI - The anti-HER3 (ErbB3) therapeutic antibody 9F7-F11 induces HER3 ubiquitination and degradation in tumors through JNK1/2- dependent ITCH/AIP4 activation. AB - We characterized the mechanism of action of the neuregulin-non-competitive anti HER3 therapeutic antibody 9F7-F11 that blocks the PI3K/AKT pathway, leading to cell cycle arrest and apoptosis in vitro and regression of pancreatic and breast cancer in vivo. We found that 9F7-F11 induces rapid HER3 down-regulation. Specifically, 9F7-F11-induced HER3 ubiquitination and degradation in pancreatic, breast and prostate cancer cell lines was driven mainly by the itchy E3 ubiquitin ligase (ITCH/AIP4). Overexpression of the ITCH/AIP4 inhibitor N4BP1 or small interfering RNA-mediated knockdown of ITCH/AIP4 inhibited HER3 ubiquitination/degradation and PI3K/AKT signaling blockade induced by 9F7-F11. Moreover, 9F7-F11-mediated JNK1/2 phosphorylation led to ITCH/AIP4 activation and recruitment to HER3 for receptor ubiquitination and degradation. ITCH/AIP4 activity was activated by the deubiquitinases USP8 and USP9X, as demonstrated by RNA interference. Taken together, our results suggest that 9F7-F11-induced HER3 ubiquitination and degradation in cancer cells mainly occurs through JNK1/2 dependent ITCH/AIP4 activation. PMID- 27203744 TI - TAT-IL-24-KDEL-induced apoptosis is inhibited by survivin but restored by the small molecular survivin inhibitor, YM155, in cancer cells. AB - Interleukin-24 (IL-24) is a cytokine belonging to the IL-10 gene family. This cytokine selectively induces apoptosis in cancer cells, without harming normal cells, through a mechanism involving endoplasmic reticulum (ER) stress response. TAT-IL-24-KDEL is a fusion protein that efficiently enters the tumor cells and locates in the ER. Here we report that TAT-IL-24-KDEL induced apoptosis in human cancer cells, mediated by the ER stress cell death pathway. This process was accompanied by the inhibition of the transcription of an antiapoptotic protein, survivin. The forced expression of survivin partially protected cancer cells from the induction of apoptosis by TAT-IL-24-KDEL, increased their clonogenic survival, and attenuated TAT-IL-24-KDEL-induced activation of caspase-3/7. RNA interference of survivin markedly sensitized the transformed cells to TAT-IL-24 KDEL. Survivin was expressed at higher levels among isolated clones that resistant to TAT-IL-24-KDEL. These observations show the important role of survivin in attenuating cancer-specific apoptosis induced by TAT-IL-24-KDEL. The pharmacological inhibition of survivin expression by a selective small-molecule survivin suppressant YM155 synergistically sensitized cancer cells to TAT-IL-24 KDEL-induced apoptosis in vitro and in vivo. The combined regimen caused significantly higher activation of ER stress and dysfunction of mitochondria than either treatment alone. As survivin is overexpressed in a majority of cancers, the combined TAT-IL-24-KDEL and YM155 treatment provides a promising alternative to the existing therapies. PMID- 27203742 TI - Glutaredoxin 3 promotes nasopharyngeal carcinoma growth and metastasis via EGFR/Akt pathway and independent of ROS. AB - Glutaredoxin 3 (GLRX3) is antioxidant enzyme, maintaining a low level of ROS, thus contributing to the survival and metastasis of several types of cancer. However, the expression and functions of GLRX3 have not been addressed in nasopharyngeal carcinoma (NPC). In this study, we found that GLRX3 was overexpressed in NPC. Knockdown of GLRX3 in NPC cell lines inhibited proliferation in vitro, tumorignesis in vivo, and colony formation. In addition, GLRX3 knockdown decreased the migration and invasion capacity of NPC cells by reversing the epithelial-mesenchymal transition (EMT). Furthermore, stabilization of GLRX3 was positively related to with epidermal growth factor receptor (EGFR) expression and negatively with ROS generation. Phosphorylation of Akt, a key downstream effector, was induced by EGFR signaling but did not rely on increasing ROS level in NPC cells. GLRX3 might be an oncoprotein in NPC, playing important roles in increasing redox reaction and activating EGFR/ Akt signals, so it may be a therapeutic target for NPC. PMID- 27203746 TI - Structure and gene cluster of the O-antigen of Escherichia coli O133. AB - The O-specific polysaccharide (O-antigen) of Escherichia coli O133 was obtained by mild acid hydrolysis of the lipopolysaccharide of E. coli O133. The structure of the hexasaccharide repeating unit of the polysaccharide was elucidated by (1)H and (13)C NMR spectroscopy, including a two-dimensional (1)H-(1)H ROESY experiment: Functions of genes in the O-antigen gene cluster were putatively identified by comparison with sequences in the available databases and, particularly, an encoded predicted multifunctional glycosyltransferase was assigned to three alpha-l-rhamnosidic linkages. PMID- 27203745 TI - Effects of substrate stiffness and cell-cell contact on mesenchymal stem cell differentiation. AB - The mechanical properties of the microenvironment and direct contact-mediated cell-cell interactions are two variables known to be important in the determination of stem cell differentiation fate, but little is known about the interplay of these cues. Here, we use a micropatterning approach on polyacrylamide gels of tunable stiffnesses to study how homotypic cell-cell contacts and mechanical stiffness affect different stages of osteogenesis of mesenchymal stem cells (MSCs). Nuclear localization of transcription factors associated with osteogenesis depended on substrate stiffness and was independent of the degree of cell-cell contact. However, expression of alkaline phosphatase, an early protein marker for osteogenesis, increased only in cells with both direct contact with neighboring cells and adhesion to stiffer substrates. Finally, mature osteogenesis, as assessed by calcium deposition, was low in micropatterned cells, even on stiff substrates and in multicellular clusters. These results indicate that substrate stiffness and the presence of neighboring cells regulate osteogenesis in MSCs. PMID- 27203748 TI - Evaluation of plan quality assurance models for prostate cancer patients based on fully automatically generated Pareto-optimal treatment plans. AB - IMRT planning with commercial Treatment Planning Systems (TPSs) is a trial-and error process. Consequently, the quality of treatment plans may not be consistent among patients, planners and institutions. Recently, different plan quality assurance (QA) models have been proposed, that could flag and guide improvement of suboptimal treatment plans. However, the performance of these models was validated using plans that were created using the conventional trail-and-error treatment planning process. Consequently, it is challenging to assess and compare quantitatively the accuracy of different treatment planning QA models. Therefore, we created a golden standard dataset of consistently planned Pareto-optimal IMRT plans for 115 prostate patients. Next, the dataset was used to assess the performance of a treatment planning QA model that uses the overlap volume histogram (OVH). 115 prostate IMRT plans were fully automatically planned using our in-house developed TPS Erasmus-iCycle. An existing OVH model was trained on the plans of 58 of the patients. Next it was applied to predict DVHs of the rectum, bladder and anus of the remaining 57 patients. The predictions were compared with the achieved values of the golden standard plans for the rectum D mean, V 65, and V 75, and D mean of the anus and the bladder. For the rectum, the prediction errors (predicted-achieved) were only -0.2 +/- 0.9 Gy (mean +/- 1 SD) for D mean,-1.0 +/- 1.6% for V 65, and -0.4 +/- 1.1% for V 75. For D mean of the anus and the bladder, the prediction error was 0.1 +/- 1.6 Gy and 4.8 +/- 4.1 Gy, respectively. Increasing the training cohort to 114 patients only led to minor improvements. A dataset of consistently planned Pareto-optimal prostate IMRT plans was generated. This dataset can be used to train new, and validate and compare existing treatment planning QA models, and has been made publicly available. The OVH model was highly accurate in predicting rectum and anus DVHs. For the bladder, larger prediction errors were observed. PMID- 27203747 TI - Relation between Liver Transaminases and Dyslipidaemia among 2-10 y.o. Northern Mexican Children. AB - BACKGROUND AND AIMS: The increase in overweight and obese children may be linked to increased rates of liver damage and dyslipidaemia. This study aimed to explore the associations of liver biomarkers with overweight/obesity and dyslipidaemia in Mexican children. METHODS: The study was a population-based cross-sectional nutritional survey carried out in the State of Nuevo Leon, Mexico. The study included a 414 subjects aged between 2 and 10 years old (47.8% girls) who took part in the State Survey of Nutrition and Health-Nuevo Leon 2011/2012. Associations between alanine aminotransferase (ALT) and aspartate aminotransferase (AST), ALT/AST ratio, and major components of serum lipid profile were assessed. RESULTS: Children with high ALT (defined as >=P75) showed higher prevalence of dyslipidaemia than their counterparts, with high prevalence of high TChol (P = 0.053), non-HDL-chol, TG, and low HDL-chol. Children with an AST/ALT >=T3 ratio were 0.43-times (95% CI: 0.25-0.74) and 0.27-times (95% CI: 0.17-0.44) low likely to be overweight/obese and to have dyslipidaemia than those with an AST/ALT